@article {pmid40657927, year = {2025}, author = {Robinson, JM and Crino, OL and Camargo, A and Breed, MF}, title = {Does a microbial-endocrine interplay shape love-associated emotions in humans? A hypothesis.}, journal = {mSystems}, volume = {}, number = {}, pages = {e0041525}, doi = {10.1128/msystems.00415-25}, pmid = {40657927}, issn = {2379-5077}, abstract = {Emerging evidence suggests that the human gut microbiome plays a regulatory role in the endocrine system, influencing hormone activity and potentially shaping the emotional and physiological dimensions of behaviors such as aggression and emotional states, including love. Here, we review the hypothesis that microbial-endocrine interactions shape love-associated emotions by modulating hormone levels and activity. While the division of love into discrete components such as lust, attraction, and attachment is somewhat artificial and may not fully capture the complexity of human experience, the associated emotions nevertheless correspond to well-characterized neuroendocrine processes. Psycho-endocrinological theory proposes that the complex and nonlinear interplay between testosterone, estradiol, and other hormones drives emotions associated with lust; serotonin and dopamine play a role in emotions linked to attraction; and oxytocin and vasopressin influence the modulation of attachment and social bonds. Microbial communities may influence emotions and relationship dynamics through effects on the hormonal pathways linked to love-associated emotions. While non-human animal studies suggest microbiota can impact social bonding, sexual preferences, and stress-related behaviors, direct evidence in humans remains limited. Investigating the evolutionary underpinnings of microbial-endocrine interactions could provide insights into how microbes influence emotions beyond love, including hate and aggression-with important societal implications. Indeed, understanding these mechanisms could have profound implications for human relationships, mental health, and even therapeutic interventions targeting the microbiota-gut-brain axis. Future research is needed to unravel the extent to which microbiomes contribute to the neurobiology of love (and other emotions) and whether manipulating microbial communities could modulate emotional and social behaviors.IMPORTANCELove is often considered an abstract emotion, but emerging science suggests that it may be shaped by the microscopic inhabitants of our bodies: microbes. This paper explores the intriguing hypothesis that microbes can influence the hormonal and neural systems linked to love-associated emotions-via the microbiota-gut-brain axis. Drawing on animal studies and early human microbiome and endocrine research, we highlight how microbes modulate neurohormones like oxytocin, dopamine, and testosterone, which play key roles in social bonding. By regulating these systems, microbes may also shape emotional and behavioral responses. This research opens new avenues for understanding not just the (micro)biology of love but also the potential for microbiome-targeted therapies to support relational well-being. By linking microbiome and emotion science, the article raises the important question of whether love is a phenomenon influenced by our resident symbionts, adding an intriguing and potentially impactful dimension to our understanding of human connection and behavior.}, }
@article {pmid40655157, year = {2025}, author = {Pena-Amelunxen, G and Asghari, M and Khatri, K and Glesner, J and Versteeg, SA and van Ree, R and Chapman, MD and Smith, SA and Chruszcz, M and Pomés, A and Aglas, L}, title = {Pre-clinical allergenicity assessment of IgE epitope-targeted Der p 2 mutants demonstrate potential as hypoallergenic AIT candidates.}, journal = {Frontiers in immunology}, volume = {16}, number = {}, pages = {1623920}, pmid = {40655157}, issn = {1664-3224}, mesh = {*Immunoglobulin E/immunology ; *Antigens, Dermatophagoides/immunology/genetics ; Animals ; Humans ; *Epitopes/immunology/genetics ; *Arthropod Proteins/immunology/genetics ; Rats ; Mutation ; Antibodies, Monoclonal/immunology ; *Desensitization, Immunologic/methods ; *Allergens/immunology/genetics ; Epitope Mapping ; *Hypersensitivity/immunology ; *Cysteine Endopeptidases/immunology/genetics ; Cell Line, Tumor ; }, abstract = {BACKGROUND: Advancements in hybridoma technology have enabled the production of human IgE monoclonal antibodies (hIgE mAb) for successful IgE epitope mapping of major allergens. Here, we assessed the hypoallergenicity of three IgE-epitope mutants (single 4C8 or 2F10, and double 4C8 + 2F10 epitope mutants) of house dust mite allergen (HDM) Der p 2.<br><br>METHODS: Humanized rat basophilic leukemia (huRBL) cells, passively sensitized overnight with either pairs of Der p 2 specific hIgE mAb (2F10, 4C8 or 2G1) or HDM-allergic serum (n=8), were stimulated with either wildtype (WT) Der p 2 or an epitope mutant and mediator release was measured.<br><br>RESULTS: No degranulation was induced upon stimulation with all mutants, when cells were sensitized with pairs of hIgE mAb specific for at least one mutated epitope. HIgE mAb specific for non-mutated epitopes led to mediator release comparable to WT Der p 2, indicating that epitopes recognized by the three different hIgE mAb are not overlapping and that the 3D-structure of the mutants is conserved. The double 4C8 + 2F10 epitope mutant had a significantly reduced maximal mediator release (48.3%) compared to the WT, in cells sensitized with allergic donor serum. Overall, the area-under-the-curve of mediator release curves induced by the mutants was significantly lower (31-65%) compared to WT. When comparing the EC20, the double 4C8 + 2F10 epitope mutant required a 158-fold higher antigen concentration to induce the same extent of mediator release as WT Der p 2.<br><br>CONCLUSION: Der p 2 epitope mutants display significantly reduced allergenicity. Particularly, the double 4C8 + 2F10 epitope mutant demonstrated a strong potential as a novel AIT vaccine candidate.}, }
@article {pmid40653356, year = {2025}, author = {Sarath Krishnan, MP and Goyal, B and Nampui, L and Gupta, SC}, title = {The role of microbiome in gastrointestinal cancer.}, journal = {International review of cell and molecular biology}, volume = {395}, number = {}, pages = {67-98}, doi = {10.1016/bs.ircmb.2024.12.009}, pmid = {40653356}, issn = {1937-6448}, mesh = {Humans ; *Gastrointestinal Neoplasms/microbiology/pathology/therapy ; *Gastrointestinal Microbiome ; Animals ; }, abstract = {The human microbiome consists of the diverse microorganisms with their equally diverse functional abilities that have evolved over millions of years with humans. This microbiome creates a mutually beneficial symbiotic relationship with their host. Through their varied functions, the human gut microbiota is crucial for preserving health and homeostasis. Any imbalance in this microbial population can lead to an array of diseased states, including cancer especially of the gastrointestinal system. The focus of this chapter is to discuss the mechanisms through which the gut microbiome creates a conducive environment for initiation and progression of cancer. In addition, the effect of microbial products such as short chain fatty acids, bile acids and Trimethylamine N-oxide on the formation of gastrointestinal cancer is also discussed. The various experimental methods and new molecular techniques that have facilitated the characterization and study of microorganisms is also discussed. The developments in microbiome research have shed light on the potential role of gut microbiota for novel biomarker discovery and therapeutic interventions in gastrointestinal cancer, like fecal microbiota transplantation. The prospects of these areas for further exploration are discussed.}, }
@article {pmid40653354, year = {2025}, author = {Gupta, R and Gaur, S}, title = {Effect of diet and lifestyle on microbiome composition.}, journal = {International review of cell and molecular biology}, volume = {395}, number = {}, pages = {157-174}, doi = {10.1016/bs.ircmb.2024.12.008}, pmid = {40653354}, issn = {1937-6448}, mesh = {Humans ; *Life Style ; *Diet ; *Microbiota ; Animals ; }, abstract = {Microbes are major drivers of many important physiological pathways in the human body. A well-adapted and established microbial community at key body sites performs a wide range of functions, including digestive and immunological roles. However, the structure of these microbial communities depends on numerous factors, both genetic and external. Diet and lifestyle are the most common external factors influencing microbiome composition. A healthy diet and lifestyle promote the growth of beneficial microbes, while disturbances in these factors can alter the entire microbial dynamics, potentially leading to pathogenesis. These perturbations can occur at any stage of life, from birth to old age, and may result in serious clinical conditions such as obesity, diabetes, cancers, metabolic syndromes, and many others. Therefore, it is essential to identify the dietary and lifestyle factors that support a healthy microbiome and prevent dysbiosis. This chapter aims to discuss the role of various component of diet and life style that can ultimately shape the human microbiome.}, }
@article {pmid40647535, year = {2025}, author = {Palkovsky, M and Modrackova, N and Neuzil-Bunesova, V and Liberko, M and Hlodakova, A and Soumarova, R}, title = {Role of Human Microbiome in Development and Management of Head and Neck Squamous Cell Carcinoma.}, journal = {Cancers}, volume = {17}, number = {13}, pages = {}, doi = {10.3390/cancers17132238}, pmid = {40647535}, issn = {2072-6694}, abstract = {Despite decades of research, cancer remains a major global health problem [...].}, }
@article {pmid40643244, year = {2025}, author = {Seekatz, AM}, title = {Straining to define a healthy microbiome.}, journal = {mSphere}, volume = {}, number = {}, pages = {e0079724}, doi = {10.1128/msphere.00797-24}, pmid = {40643244}, issn = {2379-5042}, abstract = {In 2020, I wrote an mSphere of Influence commentary on two studies that shaped my research perspective on the human gut microbiome (McNulty et al., Sci Transl Med 3:106ra106, 2011, https://doi.org/10.1126/scitranslmed.3002701; Hamilton et al., Gut Microbes 4:125, 2013, https://doi.org/10.4161/gmic.23571). The microbiome field has continued to progress since the publication of these studies over 10 years ago, emerging as a considerable factor in almost all areas focused on disease development. My previous commentary highlighted two areas that piqued my interest early on in my career: (i) that the extant microbial community should be considered when proposing to manipulate the microbiota, such as via probiotics or fecal microbiota transplantation, and (ii) that realized (i.e., transcribed) functional changes of the microbiota may occur independent of changes in its composition. Since writing that commentary, two microbiota-based therapeutics for the treatment of Clostridioides difficile infection have been approved, highlighting the potential success of using the microbiota to treat or prevent disease. Despite these wins and ever-growing evidence of the importance of the microbiome in managing our health, translating mechanistic studies into therapeutic value has been slower. In this minireview, I expand upon two large questions that would increase our ability to translate the microbiome into therapies, highlighting both historical and recent progress.}, }
@article {pmid40642982, year = {2025}, author = {Qi, X and Zhang, M and Wei, T and Lin, J and Zhao, X and Yao, Y and Hu, Y and Zheng, Y}, title = {LorDist: a novel method for calculating the distance based on functional data analysis with application to longitudinal microbial data.}, journal = {Microbiology spectrum}, volume = {}, number = {}, pages = {e0154225}, doi = {10.1128/spectrum.01542-25}, pmid = {40642982}, issn = {2165-0497}, abstract = {Longitudinal human microbial data offer insights into microbiome dynamics over time. Traditional methods usually overlook temporal relationships among samples from the same subject. Here, we presented the Longitudinal Microbial Data Distance (LorDist) method, which uses functional data fitting to construct a distance matrix integrating information from the same subject at different time points. Simulation data showed that LorDist handled well up to 60% sparseness and worked robustly with various sequencing depths and time points. Empirical data analysis demonstrated that LorDist excels in capturing differences across subjects with longitudinal microbiome data. LorDist presented the potential of longitudinal microbial data in addressing temporal autocorrelation and distinguishing phenotypes.IMPORTANCELongitudinal analysis of the human microbiome is critical for understanding its dynamic role in health and disease. However, current analytical approaches struggle to address key challenges, such as data sparsity and irregular sampling, inherent to time-series microbiome studies. Here, we developed longitudinal microbial data distance (LorDist), an innovative method leveraging functional data analysis to model temporal microbial dynamics with enhanced precision. Compared to existing methods, LorDist consistently outperforms in discerning biologically meaningful group differences, even in highly sparse data sets or under fluctuating sequencing depths. Our findings demonstrate LorDist's robust performance on real-world data sets involving inflammatory bowel disease and infant gut development. By explicitly preserving the temporal structure inherent in microbiome data, LorDist enables robust detection of subtle yet critical biological shifts, paving the way for improved diagnostics and personalized therapeutic strategies in microbiome science.}, }
@article {pmid40642105, year = {2025}, author = {Jasemi, SK and Faridafshar, H and Amin, MN and Babamohamadi, M and Falahati, M and Amirian, R and Izadi, Z}, title = {NO: a key player in microbiome dynamics and cancer pathogenesis.}, journal = {Frontiers in cellular and infection microbiology}, volume = {15}, number = {}, pages = {1532255}, pmid = {40642105}, issn = {2235-2988}, mesh = {Humans ; *Neoplasms/pathology/metabolism/microbiology/etiology ; *Nitric Oxide/metabolism ; *Microbiota/physiology ; Mouth/microbiology ; Nitrates/metabolism ; Animals ; Bacteria/metabolism ; }, abstract = {The human microbiome refers to the genomic content of microorganisms inhabiting the human body, including the lungs, oral cavity, intestinal tract, esophagus, and other areas. The human oral microbiota is a diverse and complex ecosystem that includes bacteria, microeukaryotes, archaea, and viruses. These communities have a highly structured biogeography resulting from the various microenvironments in the oral cavity, shaping local metabolic exchange. Dietary nitrate (NO3 [-]) is an ion naturally present in vegetables, especially leafy greens. When consumed, it leads to the production of nitric oxide (NO). This bioactive molecule benefits bodily functions like host defense and neuronal communication and improves vascular and metabolic health. Dietary NO3 [-] is reduced to NO via the nitrate-nitrite-NO pathway, facilitated by nitrate-reducing bacteria inside the oral cavity. NO has a leading role in different types of diseases, including cancer, cardiovascular disease, and diabetes. The bioavailability of NO is greatly enhanced by the activity of bacteria residing in the mouth, which reduces NO3 [-]to NO2 [-] and increases the concentration of circulating NO2 [-]. NO is the key to causing different malignancies, including gastrointestinal cancers. NO can cause cell death by inducing DNA damage and anti-apoptotic signaling pathways. Low to moderate levels of NO derived from tumors can activate angiogenesis and promote an invasive phenotype, while high levels of NO may have an anti-tumor effect in protecting against cancer. In this review, we intend to discuss the human microbiome, dietary NO3 [-]consumption, the vital role of NO in the human body, types of cancers, and treatments based on it.}, }
@article {pmid40638549, year = {2025}, author = {Dasgupta, S}, title = {Unraveling the Microbiome-Asthma Axis: Metagenomic Insights from Airway and Gut Microbial Communities.}, journal = {Omics : a journal of integrative biology}, volume = {}, number = {}, pages = {}, doi = {10.1177/15578100251358958}, pmid = {40638549}, issn = {1557-8100}, abstract = {Asthma is a heterogeneous respiratory disease with complex pathogenesis involving immune dysregulation, environmental triggers, and increasingly recognized to have contributions from the human microbiome. Emerging evidence from longitudinal birth cohorts and multi-omics studies reveals that early-life microbial colonization patterns in both the gastrointestinal and respiratory tracts play a crucial role in shaping immune trajectories and influencing asthma susceptibility. This expert review highlights the findings from pivotal studies that associate dysbiosis in the gut and airway microbiota with asthma development and its diverse phenotypic manifestations. Reduced abundance of immunomodulatory genera such as Bifidobacterium, Faecalibacterium, and Lachnospira in the gut has been consistently associated with increased asthma risk. In the airways, increased colonization by potentially pathogenic taxa, including Moraxella, Haemophilus, and Streptococcus, correlates with viral respiratory infections and persistent wheezing. Microbiome diversity patterns also differ between asthma phenotypes: eosinophilic asthma typically features a community profile closer to healthy individuals, while neutrophilic asthma is marked by enrichment of pro-inflammatory bacterial species. Moreover, protective genera such as Dolosigranulum and Corynebacterium in the upper airways are associated with lower risk of asthma and reduced respiratory infections. Elucidating these microbiome-mediated mechanisms holds promise for the development of targeted microbiota-based strategies for asthma prevention and phenotype-specific therapeutic interventions. The present review unpacks these localized microbial patterns and their mechanistic implications for asthma development, severity, and endotypic variation. Finally, unraveling the microbiome-asthma axis from airway and gut microbial communities also has implications for new ways of thinking personalized medicine in the future.}, }
@article {pmid40638496, year = {2025}, author = {Hyvönen, S and Solasaari, T and Pokka, T and Korpela, K and de Vos, WM and Salonen, A and Ruuska-Loewald, T and Kolho, KL}, title = {Maternal Prenatal and Postnatal Stress and Infections in Infancy.}, journal = {Acta paediatrica (Oslo, Norway : 1992)}, volume = {}, number = {}, pages = {}, doi = {10.1111/apa.70228}, pmid = {40638496}, issn = {1651-2227}, support = {5044//Signe and Ane Gyllenberg Foundation/ ; 200141/WT_/Wellcome Trust/United Kingdom ; 210168//Lastentautien Tutkimuss&#xe4;&#xe4;ti&#xf6;/ ; 5851//Finnish Medical Foundation/ ; //Juho Vainio Foundation/ ; 329/31/2015//Tekes/Business Finland/ ; }, abstract = {AIM: To study maternal stress as a possible risk factor for early infections in infants in a well-characterised, prospective infant HELMi cohort.<br><br>METHODS: We measured maternal stress during the last trimester with questionnaires (4 items, scales 0-100) and breastmilk cortisol levels at 3&#x2009;months. We compared maternal stress between infants with several infections (n&#x2009;=&#x2009;125) and infants with no infections (n&#x2009;=&#x2009;122) during the first 6 months of life. The episodes and days with symptoms were recorded using an online diary. Control subjects were matched for sex, year of birth, mode of delivery, and timing of breastmilk sample. The analysis was adjusted for season of birth and number of siblings.<br><br>RESULTS: The median maternal prenatal stress, related to household during the last trimester, was higher in the infection group than in controls (37 [IQR 19.5-61] vs. 19 [7.8-42.3]; p&#x2009;=&#x2009;0.02). There was no difference in prenatal stress related to pregnancy or the relationship between the groups. The breastmilk cortisol levels did not differ between the groups (medians of 6.8&#x2009;nmol/L [IQR 4.8-8.8] and 6.2&#x2009;nmol/L [4.5-8.4], respectively; p&#x2009;=&#x2009;0.12).<br><br>CONCLUSION: Prenatal stress was linked to the occurrence of infections in infancy. Whether support for stress reduction may reduce the risk for infections warrants further study.}, }
@article {pmid40626521, year = {2025}, author = {Wan, H and Weng, J and Cai, J and Chen, Z and Li, P and Han, J and Li, Z and Wan, Z and Yuan, Z and Gan, Y and Huang, M and Li, X and Li, T and Liu, X and Wang, X and Yu, H and Liu, B and Lin, J and Luo, Y}, title = {Nodal Downstaging in Rectal Cancer Patients: Survival is Promising if YpN0 is Achieved.}, journal = {Diseases of the colon and rectum}, volume = {}, number = {}, pages = {}, doi = {10.1097/DCR.0000000000003846}, pmid = {40626521}, issn = {1530-0358}, abstract = {BACKGROUND: Locally advanced rectal cancer is a critical health concern, with neoadjuvant therapy emerging as a pivotal strategy to enhance survival rates.<br><br>OBJECTIVE: This study aims to evaluate the prognostic value of achieving ypN0 status following neoadjuvant therapy patients with locally advanced rectal cancer, comparing survival outcomes among natural N0, downstaged N0, and ypN + groups.<br><br>DESIGN: We conducted a post hoc analysis of the FOWARC trial, employing Kaplan-Meier survival analysis and Cox regression models to assess overall survival, disease-free survival, and locoregional recurrence-free survival.<br><br>SETTINGS: The multicenter, randomized phase III FOWARC trial was conducted across 15 hospitals in China, adhering to ethical standards.<br><br>PATIENTS: Our cohort included 449 patients with locally advanced rectal cancer who underwent neoadjuvant chemoradiotherapy followed by total mesorectal excision.<br><br>INTERVENTIONS: Neoadjuvant chemoradiotherapy followed by total mesorectal excision.<br><br>MAIN OUTCOME MEASURES: The primary endpoint was 5-year overall survival, with secondary endpoints being 3-year disease-free survival and 3-year locoregional recurrence-free survival.<br><br>RESULTS: The 5-year overall survival for natural N0 and downstaged N0 groups were 88% and 89%, respectively, significantly higher than the 73% observed in the ypN+ group (p = 0.0034). The complete pathological response rate was markedly lower in the ypN+ group. Multivariable analysis showed the ypN stage as an independent prognostic factor for overall survival.<br><br>LIMITATIONS: The study's retrospective design may introduce potential biases in patient selection and preoperative staging.<br><br>CONCLUSIONS: Achieving ypN0 status via neoadjuvant chemoradiotherapy significantly improves survival in patients with locally advanced rectal cancer, regardless of ypT or cN status. This status not only serves as an independent prognostic factor, but may also help to guide hypothesis-driven, individualized postoperative-treatment strategies. See Video Abstract.ClinicalTrials.gov identifier: NCT01211210.}, }
@article {pmid40626364, year = {2025}, author = {Sequoia, JA and Haddock, NL and Gay, PM and Barkal, LJ and Narasimhan, P and Martinez, N and Winn, VD and Bollyky, PL}, title = {Identification of bacteriophage DNA in human umbilical cord blood.}, journal = {JCI insight}, volume = {10}, number = {13}, pages = {}, doi = {10.1172/jci.insight.183123}, pmid = {40626364}, issn = {2379-3708}, mesh = {Humans ; *Fetal Blood/virology ; Female ; Pregnancy ; *DNA, Viral/blood/genetics/isolation &amp; purification ; *Bacteriophages/genetics/isolation &amp; purification ; Adult ; Infant, Newborn ; Pre-Eclampsia/virology/blood ; Cell-Free Nucleic Acids/blood ; Chorioamnionitis/virology/blood ; Premature Birth/virology/blood ; }, abstract = {Bacteriophages, viruses that parasitize bacteria, are abundant in the human microbiome and may influence human health, in part, through their interactions with bacterial hosts. Whether endogenous bacteriophages or their products are vertically transmitted from mother to fetus during human pregnancy is not known. Here, we searched for bacteriophage sequences from five bacteriophage databases (474,031 total sequences) in cell-free DNA (cfDNA) of paired maternal and umbilical cord blood samples from two independent cohorts. First, we sequenced cfDNA from 10 pairs of maternal and cord blood samples, including four pairs affected by preeclampsia. We validated our findings in a previously published dataset of 62 paired maternal and cord blood samples, including 43 pairs from preterm or chorioamnionitis-affected deliveries. We identified 94 and 596 bacteriophage sequences in maternal and cord blood cfDNA samples from the first and second cohort, respectively. We identified 58 phage sequences across maternal-infant dyads and 581 phage sequences that were unique to a single sample. We did not identify any phage sequences consistently associated with preeclampsia, preterm, or chorioamnionitis-affected samples. This study demonstrated the presence of bacteriophage DNA in human cord blood at birth, providing evidence that the human fetus is exposed to bacteriophage DNA in utero.}, }
@article {pmid40623769, year = {2025}, author = {Basoya, R and Singh, B and Basi, A and Aggarwal, S}, title = {Role of microbiome in cancer progression.}, journal = {International review of cell and molecular biology}, volume = {394}, number = {}, pages = {79-106}, doi = {10.1016/bs.ircmb.2024.12.013}, pmid = {40623769}, issn = {1937-6448}, mesh = {Humans ; *Neoplasms/microbiology/pathology/therapy ; *Disease Progression ; *Microbiota ; Animals ; }, abstract = {The human microbiome plays a crucial role in maintaining health and preventing disease. Dysbiosis, or imbalance, in the microbiome, has been linked to various diseases, including cancer. This chapter explores the influence of microbiomes on different organs, immune system modulation, and cancer development. Specific microorganisms, such as Helicobacter pylori, Escherichia coli, and human papillomavirus (HPV), contribute to gastric, colorectal, and cervical cancer through mechanisms like immunomodulation and proliferative signaling pathways. Dysbiosis-induced cancer progression involves NF-κB, Wnt/β-catenin, and JAK/STAT signaling. Recent studies highlight the microbiome's potential in cancer diagnosis and immunotherapy. Fecal Microbiota Transplantation (FMT) and predictive biomarkers, such as Porphyromonas gingivalis and Escherichia-Shigella, show promise in treating colorectal cancer. The microbiome influences tumor biology and immune response, affecting immunotherapeutic efficacy. Understanding microbiome-cancer interactions offers new opportunities for improved diagnosis and personalized therapy. This chapter provides comprehensive insights into the role of microbiome in cancer progression, emphasizing the importance of microbiome research in developing effective cancer treatments.}, }
@article {pmid40623763, year = {2025}, author = {Agrawal, P and Mendhey, P and Kumar, R and Patel, S and Kaushik, PK and Dadsena, A and Kumar, S}, title = {Introduction to microbiomes in health and diseases.}, journal = {International review of cell and molecular biology}, volume = {394}, number = {}, pages = {1-42}, doi = {10.1016/bs.ircmb.2024.12.010}, pmid = {40623763}, issn = {1937-6448}, mesh = {Humans ; *Microbiota ; *Health ; *Disease ; Animals ; }, abstract = {The human microbiome is a complex ecological system of commensal, symbiotic, and pathogenic microorganisms that plays a crucial role in human health and disease. The microbiome includes both the living microorganisms also called microbiota and their synthesized metabolites and structural components. It is distributed to the gastrointestinal tract, skin, respiratory system, and oral cavity, each with a distinct microbial composition. Dysbiosis, or imbalance in the microbiome is linked to numerous diseases such as eczema, gastric ulcers, cardiovascular diseases, and cancer. The axes of microbial activity and their connections to disease, including the gut-skin, gut-lung, gut-brain, and gut-kidney play a crucial role in health and disease conditions. Also, the role of the microbiome in cancer development and response to therapy is examined. This book chapter underscores the importance of maintaining a balanced microbiome for overall health and the potential for microbiome-based interventions in disease prevention and treatment.}, }
@article {pmid40621920, year = {2025}, author = {Ventin-Holmberg, R and Eriksson, J and Eberl, A and Sipponen, T and Nissilä, E and Saavalainen, P}, title = {The total gut mucosal and fecal bacterial load increases in successful treatment of inflammatory bowel disease with infliximab.}, journal = {Microbiology spectrum}, volume = {}, number = {}, pages = {e0189424}, doi = {10.1128/spectrum.01894-24}, pmid = {40621920}, issn = {2165-0497}, abstract = {Inflammatory bowel diseases (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), are chronic inflammatory gastrointestinal disorders linked to genetic predisposition and environmental factors. The gut microbiota, composed of various microorganisms, plays a crucial role in IBD, as reduced anaerobic bacteria and short-chain fatty acid (SCFA) producers are associated with predisposition to IBD. There is no cure for IBD, but the treatment aims for mucosal healing including conventional treatment and biological therapies such as infliximab (IFX). IFX, a tumor necrosis factor alpha (TNF-α) blocker, effectively reduces inflammation, but around 50% of patients do not achieve long-term remission. Fecal samples were collected from 70 patients with IBD (24 CD, 44 UC, and 2 IBDU), and mucosal samples were collected from both ileum and colon from 63 patients before, during, and after IFX treatment. The bacterial microbiota composition was investigated by targeting the conserved 16S region in MiSeq sequencing. Additionally, the relative sequencing data were quantified by qPCR. Responders to IFX had an increase in the total bacterial load in ileum and fecal samples during treatment, primarily driven by butyrate-producing bacteria in the Firmicutes phylum. Interestingly, this was only observed in the fecal samples in responders, but not non-responders to IFX. These results indicate that the gut bacterial microbiota of responders to IFX is changing toward a more favorable composition during successful IFX treatment.IMPORTANCEThe research described in this paper enhances our understanding of how infliximab (IFX) treatment affects the gut mucosal and fecal microbiota in patients with inflammatory bowel disease (IBD). Using 16S sequencing technique and quantification by qPCR, the study revealed that successful treatment with IFX led to an increase in the total bacterial load in both ileal and fecal samples, as well as a shift in bacterial composition toward a more favorable profile with an increase in butyrate-producing bacteria in the fecal samples in responders but not in non-responders to infliximab. This study emphasizes that the gut microbiota plays an important role in the healing process during infliximab treatment in IBD.}, }
@article {pmid40618318, year = {2025}, author = {Wu, K and Zhu, E and Chen, J and Kuang, Q and Lin, J and Zhao, S and Xu, X and Li, S and Sui, Y and Huang, M and Zhang, Y}, title = {Overexpression of GPX4 in diabetic rat kidney alleviates renal injury induced by ferroptosis.}, journal = {Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine}, volume = {}, number = {}, pages = {}, pmid = {40618318}, issn = {1572-8773}, abstract = {Ferroptosis-mediated injury in diabetic kidney (DKD) is receiving increasing attention. Glutathione Peroxidase 4 (GPX4) has long been considered a key protein to prevent ferroptosis, but its exact role in the progression of DKD, where this protein down-regulated, remains unclear. Thus, to clarify GPX4 in DKD progression, we have used adeno-associated viruses (AAVs) to overexpress it in kidneys of DKD rats. Streptozotocin (STZ)-induced DKD rats were injected once with GPX4-AAVs via tail vein. Renal function and kidney pathology were measured. Before and after treatment with GPX4-AAV, variations in kidney of ferroptosis-related indicators, such as GPX4, dihydroorotate dehydrogenase (DHODH), iron content, glutathione (GSH), superoxide dismutase (SOD), malondialdehyde (MDA), transferrin receptor 1 (TFR1), ferritin heavy chain (FTH), were monitored. The kidneys of STZ-treated rats showed reduced expression of GPX4, DHODH, GSH and SOD, increased expression of TFR1 and FTH, and higher levels of iron and MDA. Histopathology was consistent with renal fibrosis and thickened renal tubules. Changes were partly reversed after overexpression of GPX4, with decreased expression of FTH, together with reduced iron and MDA levels, although expression of TFR1, GSH and SOD showed no significant change. Renal function showed a lower urine protein-creatinine ratio, whereas the effect on renal fibrosis and thickened renal tubules was alleviated. Our study demonstrates that GPX4 is downregulated in DKD, and its AAV-mediated overexpression in kidney of DKD rats partly alleviates the diabetic kidney injury induced by ferroptosis.}, }
@article {pmid40616741, year = {2025}, author = {Renton, N and Pillinger, MH and Toprover, M}, title = {Gout, Hyperuricemia, and the Intestinal Microbiome.}, journal = {Inflammation}, volume = {}, number = {}, pages = {}, pmid = {40616741}, issn = {1573-2576}, abstract = {Gout is a disease of hyperuricemia (HU) leading to monosodium urate crystal deposition in the joint, resulting in inflammation and joint damage. Recently, efforts have been made to characterize the intestinal microbiome of patients who suffer from HU and gout, and pre-clinical studies have evaluated the utility of prebiotics and probiotics in alleviating gout. Herein we review recent notable studies addressing these topics. In brief, the "gouty" microbiome is characterized by reduced diversity, an elevated Bacteroides: Firmicutes ratio, and reduced presence of Akkermansia and Bifidobacterium. In anserine models, supplementation with Lactobacillus probiotic strains appears to reduce serum urate (SU) and HU-induced inflammation. Murine models suggest that the chicory-derived prebiotic inulin may reduce SU, and oral supplementation with the anti-inflammatory short-chain fatty acid butyrate may lower SU by enhancing urate excretion and alleviate HU-induced tissue inflammation. Many of these studies are limited by modest numbers of participants and/or incompletely documented experimental controls, and, in the case of animal models, questionable reproducibility in humans. Many studies have been geographically limited. There remains a need for more information regarding the features of the "gouty" microbiome in wider populations, as well as for additional well-controlled probiotic and prebiotic studies in more physiologically relevant animal models prior to clinical trials.}, }
@article {pmid40615170, year = {2025}, author = {Chowdhury, R and Maddheshiya, A and Taneja, S and Bhandari, N and Majumder, PP and Strand, TA and Pandey, RM and Kurpad, AV and Mukherjee, S}, title = {Impact of an Integrated Intervention Package During Preconception, Pregnancy, and Early Childhood on the Gut Microbiome at Six Months of Age: Findings from the Women and Infants Integrated Growth Study (WINGS) Randomized Controlled Trial.}, journal = {The Journal of nutrition}, volume = {155}, number = {7}, pages = {2355-2366}, doi = {10.1016/j.tjnut.2025.04.016}, pmid = {40615170}, issn = {1541-6100}, mesh = {Humans ; Female ; *Gastrointestinal Microbiome ; Pregnancy ; Infant ; Adult ; Young Adult ; Adolescent ; Male ; Feces/microbiology ; *Preconception Care ; }, abstract = {BACKGROUND: The infant gut microbiome is essential for healthy growth and development. However, limited research has explored how interventions targeting maternal and infant health, nutrition, and psychosocial conditions during preconception, pregnancy, and early childhood impact microbiome development. To address this research gap and better understand the potential impact of such interventions, this study was designed to evaluate their effects on the infant gut microbiome.<br><br>OBJECTIVE: The aim was to evaluate the effects of an integrated intervention package on infant gut microbiome at 6 mo of age compared with routine care.<br><br>METHODS: The study was embedded in a randomized factorial trial involving women aged 18-30 y. Participants were randomly assigned to receive either a preconception intervention package or routine care until pregnancy. Pregnant women were then randomly assigned to receive a pregnancy and early childhood intervention package or routine care. The intervention included health care for growth-related conditions, nutrition, water, sanitation, and hygiene (WASH), and psychosocial care. Stool samples from 392 infants (185 from the preconception, pregnancy, and early childhood intervention group and 207 from the routine care group) were collected at 6 mo, followed by microbiome DNA isolation and high-throughput sequencing of the V3-V4 region of 16S rRNA gene. Generalized linear models were used to estimate the mean relative abundance of core gut microbiome phyla, genera, and species between the intervention and routine care groups.<br><br>RESULTS: Infants in the group who received preconception, pregnancy, and early childhood intervention had a significantly lower mean relative abundance of Klebsiella genus under the Pseudomonadota phylum (45% lower; 95% confidence interval [CI]: 18, 63) and Klebsiella pneumoniae species (38% lower; 95% CI: 8, 59) compared with routine care group. In contrast, the relative abundance of Megasphaera (72% higher; 95% CI: 7, 175), Prevotella (72% higher; 95% CI: 3, 187), and Bifidobacterium breve (34% higher; 95% CI: 2, 79) was significantly higher in the group received preconception, pregnancy and early childhood intervention compared with routine care.<br><br>CONCLUSIONS: The findings indicate that improving maternal and infant health, nutrition, and psychosocial conditions enhances the relative abundance of beneficial gut bacteria at 6 mo of age, supporting healthy growth and development. This trial was registered at Clinical Trials Registry-India as CTRI/2020/10/028770; https://ctri.nic.in/Clinicaltrials/advsearch2.php.}, }
@article {pmid40613581, year = {2025}, author = {Dang, T and Lysenko, A and Boroevich, KA and Tsunoda, T}, title = {VBayesMM: variational Bayesian neural network to prioritize important relationships of high-dimensional microbiome multiomics data.}, journal = {Briefings in bioinformatics}, volume = {26}, number = {4}, pages = {}, doi = {10.1093/bib/bbaf300}, pmid = {40613581}, issn = {1477-4054}, support = {JP20H03240//JSPS KAKENHI/ ; JP24K15175//JSPS KAKENHI/ ; JPMJCR2231//JST CREST/ ; }, mesh = {Bayes Theorem ; *Microbiota ; *Neural Networks, Computer ; *Metagenomics/methods ; Humans ; *Computational Biology/methods ; Algorithms ; Multiomics ; }, abstract = {The analysis of high-dimensional microbiome multiomics datasets is crucial for understanding the complex interactions between microbial communities and host physiological states across health and disease conditions. Despite their importance, current methods, such as the microbe-metabolite vectors approach, often face challenges in predicting metabolite abundances from microbial data and identifying keystone species. This arises from the vast dimensionality of metagenomics data, which complicates the inference of significant relationships, particularly the estimation of co-occurrence probabilities between microbes and metabolites. Here we propose the variational Bayesian microbiome multiomics (VBayesMM) approach, which aims to improve the prediction of metabolite abundances from microbial metagenomics data by incorporating a spike-and-slab prior within a Bayesian neural network. This allows VBayesMM to rapidly and precisely identify crucial microbial species, leading to more accurate estimations of co-occurrence probabilities between microbes and metabolites, while also robustly managing the uncertainty inherent in high-dimensional data. Moreover, we have implemented variational inference to address computational bottlenecks, enabling scalable analysis across extensive multiomics datasets. Our large-scale comparative evaluations demonstrate that VBayesMM not only outperforms existing methods in predicting metabolite abundances but also provides a scalable solution for analyzing massive datasets. VBayesMM enhances the interpretability of the Bayesian neural network by identifying a core set of influential microbial species, thus facilitating a deeper understanding of their probabilistic relationships with the host.}, }
@article {pmid40611411, year = {2025}, author = {Islam, A}, title = {Advances in Microbiome Research: Implications for Infectious Disease Management and Treatment.}, journal = {Recent advances in anti-infective drug discovery}, volume = {}, number = {}, pages = {}, doi = {10.2174/0127724344384934250624040634}, pmid = {40611411}, issn = {2772-4352}, abstract = {INTRODUCTION: The human microbiome plays a pivotal role in health and disease, with microbial imbalances (dysbiosis) increasingly linked to heightened susceptibility to infections and exacerbated disease severity. This review explores how the microbiome confers protection through mechanisms, such as colonization resistance, immune modulation, and antimicrobial metabolite production, while also examining its potential as a predictive tool for infection risk and outcomes, as exemplified in COVID-19.<br><br>METHODS: This article synthesizes current literature on microbiome dynamics, leveraging advances in high-throughput sequencing, bioinformatics, and machine learning to analyze microbial profiles and identify biomarkers. It evaluates microbiome-based therapeutic strategies, including probiotics, prebiotics, and engineered microbes, and assesses challenges in translating these approaches into clinical practice.<br><br>RESULTS: Microbiome profiles demonstrate prognostic value in predicting infection risk and severity, supported by enhanced analytical tools that enable precise biomarker discovery for diagnostics and personalized medicine. Therapeutic interventions show promise in restoring microbial balance and combating infections, though clinical adoption is hindered by variability, regulatory hurdles, and the need for standardized methodologies.<br><br>CONCLUSION: Integrating microbiome insights into clinical practice requires rigorous clinical trials, standardized protocols, and resolution of ethical and regulatory challenges. Future research should focus on elucidating microbiome-host-pathogen interactions and developing targeted interventions, and advanced computational models are critical to unlocking the full potential of microbiome-based diagnostics and therapeutics for infectious disease management.}, }
@article {pmid40607434, year = {2025}, author = {Kim, SI and Rha, MS and Kim, J and Ahn, SH and Ryu, JH and Cho, HJ and Kim, CH}, title = {Inflammation-driven periostin in ECRS has contrasting effects on tissue structural integrity and osteitis.}, journal = {Frontiers in immunology}, volume = {16}, number = {}, pages = {1596746}, pmid = {40607434}, issn = {1664-3224}, mesh = {Animals ; *Cell Adhesion Molecules/metabolism/genetics ; Humans ; Mice ; *Sinusitis/metabolism/immunology/pathology ; Mice, Knockout ; *Osteitis/metabolism/immunology/pathology/etiology ; *Rhinitis/metabolism/immunology/pathology ; Inflammation/immunology/metabolism ; Disease Models, Animal ; Male ; Chronic Disease ; Female ; Osteogenesis ; Nasal Mucosa/metabolism/pathology/immunology ; Fibroblasts/metabolism/immunology ; *Eosinophilia/immunology/metabolism/pathology ; Periostin ; }, abstract = {INTRODUCTION: Eosinophilic chronic rhinosinusitis (ECRS) is a severe form of chronic rhinosinusitis characterized by type 2 inflammation, tissue remodeling, and bone thickening, known as osteitis. Periostin, a matricellular protein involved in extracellular matrix (ECM) regulation and T helper 2 (Th2)-mediated inflammation, is markedly elevated in patients with ECRS; however, its pathophysiological role remains unclear.<br><br>METHODS: We investigated the role of periostin in inflammation and tissue remodeling in ECRS using samples from ECRS patients, human nasal epithelial cells and fibroblasts, as well as an ECRS mouse model including periostin knockout mice.<br><br>RESULTS: Periostin levels were elevated in ECRS tissues and modestly correlated with osteitis scores. Th2 cytokines increased periostin expression, particularly in nasal fibroblasts. Conditioned medium containing periostin promoted osteogenic differentiation in vitro, whereas neutralizing antibodies reduced the expression of osteogenic markers. In an ECRS mouse model, periostin deficiency led to reduced bone thickening and lower expression of osteogenic markers despite similar eosinophil infiltration. Furthermore, periostin-deficient mice exhibited greater epithelial collapse and reduced fibronectin levels, indicating compromised ECM integrity.<br><br>DISCUSSION: These findings demonstrate that periostin contributes to osteogenesis and maintenance of structural stability in the inflamed sinonasal mucosa. Periostin may be a potential therapeutic target for controlling chronic inflammation and tissue remodeling in ECRS.}, }
@article {pmid40607343, year = {2025}, author = {Xu, H and Zhang, F and Che, Y and Cui, Y and Yao, Q and Guan, Y and Chen, H and Huang, Y}, title = {Integrative multi-omics and bioinformatics analysis of the effects of BaiRui YuPingFeng Powder on intestinal health in broilers.}, journal = {Frontiers in veterinary science}, volume = {12}, number = {}, pages = {1606531}, pmid = {40607343}, issn = {2297-1769}, abstract = {INTRODUCTION: In recent years, global poultry consumption has increased rapidly, making chicken the most widely consumed meat worldwide by 2019. To increase livestock development, antibiotics are often added to animal feed as growth promoters. But overuse of antibiotics may alter the gut microbiota, make people more resistant to them, and raise the possibility that they will spread antibiotic resistance genes to the human microbiome. Therefore, identifying safe and effective alternatives to antibiotics in livestock production is crucial for maintaining and improving gut microbial balance, ultimately promoting poultry health. The aim of this study was to investigate the mechanisms behind the impacts of BaiRui YuPingFeng Powder (TCYP) on intestinal health in broilers using combined metabolomics, bioinformatics analysis, and 16S rRNA sequencing.<br><br>METHODS: In a 42-day feeding trial, 300 one-day-old broilers were randomly divided into five groups (six replicates per group; 10 broilers per replicate) fed a basal diet with or without supplements: control (CON), antibiotic (ATB), and TCYP at 500, 1000, and 1500 mg/kg. Growth performance, serum biochemical parameters, intestinal morphology, cecal microbiota composition, and metabolomic profiles were analyzed. Bioinformatics analysis was used to identify potential targets and pathways, followed by qPCR validation of key genes.<br><br>RESULTS: Compared with the CON group, TCYP administration dose-dependently reduced the feed-to-gain ratio (F/G) and average daily feed intake (ADFI) while increasing average daily gain (ADG), with the high-dose TCYP showing more pronounced effects (p < 0.05). Serum biochemical analysis revealed that TCYP treatment significantly decreased serum levels of total cholesterol (T-CHO), triglycerides (TG), lactate dehydrogenase (LDH), and alanine aminotransferase (ALT) in a dose-dependent manner, while elevating albumin (ALB) content. These beneficial effects were particularly marked in the high-dose TCYP group (p < 0.05). Histopathological examination indicated that high-dose TCYP significantly enhanced villus height and the villus-to-crypt ratio (V/C) in the duodenum, jejunum, and ileum compared to the CON group (p < 0.05). 16S rRNA sequencing analysis revealed that TCYP treatment significantly modified the &#x3b2;-diversity of cecal microbiota (p < 0.01). Compared to the CON group, ATB treatment increased the abundance of Faecalibacterium and Lachnospiraceae_unclassified but reduced Ruminococcaceae_unclassified and Firmicutes_unclassified. Notably, dietary TCYP supplementation maintained gut microbiota profiles similar to the CON group, demonstrating its stabilizing effect on microbial community structure in broilers. Metabolomic analysis identified differential metabolites primarily involved in lipid and lipid-like molecules, organic heterocyclic compounds, and organic acids and derivatives. Spearman correlation analysis revealed significant associations between Lachnospiraceae_unclassified and metabolites such as Gly-Leu, fumarate, and phenylpyruvic acid (|r| > 0.5, p < 0.05). Bioinformatics analysis suggested that TCYP may improve intestinal health by regulating key targets, including MMP9, TGFB1, and PPARG, as well as the peroxisome proliferator-activated receptor (PPAR) signaling pathway. Quantitative PCR (qPCR) results showed that, compared to the CON group, TCYP dose-dependently significantly upregulated the mRNA expression of PPARG, PDPK1, and Bcl2 in jejunal tissues (p < 0.05), while significantly downregulating the expression of MMP1 and Bax (p < 0.05).<br><br>CONCLUSION: TCYP enhances growth performance and intestinal health in broilers through multiple mechanisms, including maintaining cecal microbial homeostasis, modulating lipid and amino acid metabolism, with potential involvement of the PPAR signaling pathway based on bioinformatics and gene expression analysis.}, }
@article {pmid40606566, year = {2025}, author = {Wang, L and Wang, L and Chen, L}, title = {NetNiche: Microbe-Metabolite Network Reconstruction and Microbial Niche Analysis.}, journal = {Phenomics (Cham, Switzerland)}, volume = {5}, number = {2}, pages = {208-211}, pmid = {40606566}, issn = {2730-5848}, abstract = {UNLABELLED: Metagenomics and metabolomics technologies have been widely used to investigate the microbe-metabolite interactions in vivo. However, the computational methods that accurately infer the microbe-metabolite interactions are lacking. We present a context-aware framework for graph representation learning, NetNiche, which predicts microbe-metabolite and microbe-microbe interactions in an accurate manner, by integrating their abundance data with prior knowledge. We applied NetNiche to datasets on gut and soil microbiome, and demonstrated that NetNiche can outperform the state-of-the-art methods, such as SParse InversE Covariance Estimation for Ecological Association Inference (SPIEC-EASI), Sparse Correlations for Compositional data (SparCC) and microbe-metabolite vectors (mmvec). NetNiche is an effective tool with wide applicability for the multi-omics study of human microbiome.<br><br>SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s43657-024-00168-8.}, }
@article {pmid40604393, year = {2025}, author = {Yao, S and Yan, X and Chen, H and Lei, S and Huang, J and Guo, K and Yu, Z}, title = {Dynamic changes of gut and skin microbiota in pancreatic cancer-induced skin injury.}, journal = {BMC microbiology}, volume = {25}, number = {1}, pages = {392}, pmid = {40604393}, issn = {1471-2180}, support = {32170071//National Natural Science Foundation of China/ ; }, }
@article {pmid40604155, year = {2025}, author = {Wen, W and Yang, C and Zuo, T}, title = {Viewing MASLD through an integrative gut microbiome lens.}, journal = {Nature metabolism}, volume = {}, number = {}, pages = {}, pmid = {40604155}, issn = {2522-5812}, }
@article {pmid40601380, year = {2025}, author = {Bağcı, U and Ulusan Bağcı, &#xd6;}, title = {The bibliometric analysis of documents concerning the relationship between the microbiota and urological malignancies.}, journal = {Journal of medical microbiology}, volume = {74}, number = {7}, pages = {}, doi = {10.1099/jmm.0.002041}, pmid = {40601380}, issn = {1473-5644}, mesh = {Humans ; *Bibliometrics ; *Microbiota ; *Urologic Neoplasms/microbiology ; Male ; Prostatic Neoplasms/microbiology ; Urinary Bladder Neoplasms/microbiology ; Kidney Neoplasms/microbiology ; }, abstract = {Introduction. The microbiota, which has a major impact on both health and illness, has recently become one of the most popular research topics.Hypothesis/Gap statement. To the best of our knowledge, no research has undertaken a bibliometric analysis of publications examining the connection between microbiome and urological cancer to date. In this respect, it is thought that our study will contribute to the literature.Aim. The purpose of this study is to raise awareness of the topic by performing a bibliometric analysis of the publications examining the connection between the microbiota and the most common urological cancers, including bladder, prostate, and kidney cancers.Methodology. All publications about prostate, renal and bladder cancers and microbiota indexed in Web of Science between 2000 and 2024 were included in the study.Results. A total of 310 publications were obtained. Before 2018, there were only three or fewer publications annually; however, following 2018, the number of publications increased rapidly, reaching a peak of 77 in 2024. The USA led with 98 (31.61%) documents, followed by China (60, 19.35%) and Italy (31, 10%). With 19 publications, Hirotsugu Uemura is the most contributing author, followed by Norio Nonomura with 17. Prostate cancer accounted for 45.48% of the publications, bladder cancer for 36.77% and kidney malignancies for 17.64%.Conclusion. Despite the fact that microbiota has been known for 80 years, research on the connection between microbiota and cancer accelerated after the completion of the Human Microbiome Project. The number of studies examining the connection between urological cancer and microbiota peaked in 2024 and is probably going to rise. More research is required on this topic, since the correlation between microbiota and especially prostate and bladder malignancies raises the possibility that variations in microbiota may be utilized in diagnosis, treatment and prognosis.}, }
@article {pmid40593076, year = {2025}, author = {Krawczyk, K and Rybaczek, D and Locht, C and Pyrzanowska-Banasiak, A and Ciołek, M and Sicinska, P and Rachubik, M and Kowalewicz-Kulbat, M}, title = {Uptake of environmental halophilic archaea by human dendritic cells.}, journal = {Scientific reports}, volume = {15}, number = {1}, pages = {21912}, pmid = {40593076}, issn = {2045-2322}, support = {2017/27/N/NZ6/02850//Narodowe Centrum Nauki/ ; }, abstract = {Halophilic archaea are a group distinct from Bacteria and Eukarya, which belong to extremophiles living in highly saline environments. However, they can also exist in the human microbiome. Their impact on the human immune system is poorly known. In this study we examined the interaction of Halorhabdus rudnickae WSM-64[T], isolated from the Barycz area of the Wieliczka Salt-Mine in Poland, and of Natrinema salaciae MDB25[T] from the brine of Lake Medee in Italy, with human monocyte-derived dendritic cells (Mo-DCs). We found that these halophilic archaea invade the cytoplasm and the nucleus of Mo-DCs, but, in contrast to intracellular bacterial pathogens, they do not cause cytotoxic effects on DCs, as no single- or double-stranded DNA breaks (SSB and DSB, respectively), nor chromatin aberrations were noted. Moreover, they did not induce cell cycle alterations, apoptosis or necrosis of DCs. Surprisingly, these halophiles were found to protect against genotoxic activities of Staphylococcus aureus enterotoxin B (SEB), as pre-incubation of the Mo-DCs with the halophilic archaea significantly reduced SEB-induced SSB and DSB, as well as cell cycle disturbance and apoptosis. Therefore, these halophilic archaea can be regarded as safe stimulators for the Mo-DCs to potentially be used as immunomodulators and protective agents for various disorders.}, }
@article {pmid40590527, year = {2025}, author = {Bridy, PV and Cruz, JC and Covington, JL and Islam, TI and Hadley, CE and Tran, K and Fry, R and Sheffield, BA and Serrano, M and Buck, GA and Zhao, J and Tossas, KY and Meyers, C and Morgan, IM and James, CD and Jefferson, KK}, title = {Human papillomavirus 16 mitigates Sneathia vaginalis-induced damage to cervical keratinocytes.}, journal = {mSphere}, volume = {}, number = {}, pages = {e0015225}, doi = {10.1128/msphere.00152-25}, pmid = {40590527}, issn = {2379-5042}, abstract = {Sneathia vaginalis is a bacterial component of the vaginal microbiome that is of clinical interest because of its association with preterm birth and other obstetric complications. It produces a cytotoxin, but little is known about the mechanism through which it kills epithelial cells or the role that cytotoxicity plays in bacterial survival. Recent microbiome studies demonstrate an association between S. vaginalis and human papillomavirus (HPV) within the female reproductive tract, suggesting that HPV and S. vaginalis could interact in some way within this shared niche. We analyzed 16S rRNA survey and HPV typing data from our Vaginal Human Microbiome Project and found, in agreement with other reports, that S. vaginalis was associated with HPV infection. To test the hypothesis that HPV promotes the growth of S. vaginalis, growth and cytotoxicity of S. vaginalis in co-culture with HPV16-positive and HPV-negative human cervical keratinocytes (HCK) were quantitatively assessed. Organotypic HCK rafts expressing HPV16 were more resistant to S. vaginalis-induced damage, as assessed by histology, and supported increased bacterial growth relative to HPV-negative HCK rafts. When S. vaginalis was co-cultured with HPV16-positive and HPV-negative HCK monolayers, cytotoxicity was observed in both HPV16-positive and HPV-negative cells, but HPV16-positive cells were more resistant to the toxic effects of the bacteria and supported bacterial growth for an extended period of time. In conclusion, HPV16 may protect cervical keratinocytes from the cytotoxic effects of S. vaginalis, preventing the eradication of colonized cells and supporting bacterial growth, and this could underlie the association between S. vaginalis and HPV in vivo.IMPORTANCESneathia vaginalis (S. vaginalis) is a bacterial species that lives in the human vagina and can cause complications during pregnancy if it invades the uterus. It is capable of killing cervical epithelial cells. Human papillomaviruses (HPV) are sexually transmitted viruses that can cause genital lesions and cervical cancer. Recently, multiple reports describe an association between S. vaginalis and HPV. This study used cultured cervical epithelial cells expressing the high-risk HPV type, HPV16, and HPV-negative cells to determine whether HPV promotes the growth of S. vaginalis. We found that HPV16 promotes the survival of cervical epithelial cells that are exposed to S. vaginalis. Survival of cervical epithelial cells may benefit the growth of S. vaginalis, which adhere to and feed off of these cells to survive in the female reproductive tract.}, }
@article {pmid40587084, year = {2025}, author = {Li, Y and He, Z and Li, C and Huang, J and Yu, Z}, title = {Mechanisms of efficacy of drug therapy in type 2 diabetes: the role of microbiomes.}, journal = {Minerva endocrinology}, volume = {}, number = {}, pages = {}, doi = {10.23736/S2724-6507.25.04306-4}, pmid = {40587084}, issn = {2724-6116}, abstract = {The gut microbiota plays a crucial role in the human body and has an impact on the physiological function of the host. In particular, changes in the gut microbiota are especially pronounced in patients with type 2 diabetes. There is ample evidence that glucose-lowering drugs exert their therapeutic effects precisely through their interactions with the gut microbiota, but there is a lack of summarization. An overall comparison of the effects of each hypoglycemic agent on the gut flora can provide new inspiration for combinations. In this paper, we selected several representative glucose-lowering drugs, such as metformin, sodium-dependent glucose transporters 2 inhibitors (dapagliflozin), glucagon-like peptide-1 receptor agonists (semaglutide, liraglutide), and the traditional Chinese medicine (berberine), and illustrated how they can affect the disease process by regulating metabolic homeostasis, immune response, and gut barrier. We found that each of these four hypoglycemic agents can have conflicting effects on the gut flora depending on the timing and mode of administration. Meanwhile, the potential impact of gut microbiota on drug safety is explored, and an outlook for the optimization of future type 2 diabetes treatment regimens is presented.}, }
@article {pmid40586597, year = {2025}, author = {Khatib, L and Song, SJ and Dilmore, AH and Sanders, JG and Brennan, C and Hernandez, AR and Myers, T and Oles, R and Farmer, S and Cowart, C and Birmingham, A and Diaz, EA and Nizet, O and Gilbert, K and Litwin, N and Das, P and Nowinski, B and Bryant, M and Tribelhorn, C and Sanders-Bodai, K and Chaumont, S and Knol, J and Roeselers, G and Laiola, M and Shetty, SA and Veiga, P and Tap, J and Derrien, M and Koutnikova, H and Cotillard, A and Lay, C and Tovar, AR and Torres, N and Arteaga, L and González, A and McDonald, D and Bartko, A and Knight, R}, title = {A three-country analysis of the gut microbiome indicates taxon associations with diet vary by taxon resolution and population.}, journal = {mSystems}, volume = {}, number = {}, pages = {e0054425}, doi = {10.1128/msystems.00544-25}, pmid = {40586597}, issn = {2379-5077}, abstract = {UNLABELLED: Emerging research suggests that diet plays a vital role in shaping the composition and function of the gut microbiota. Although substantial efforts have been made to identify general patterns linking diet to the gut microbiome, much of this research has been concentrated on a small number of countries. Additionally, both diet and the gut microbiome have highly complex and individualized configurations, and there is growing evidence that tailoring diets to individual gut microbiota profiles may optimize the path toward improving or maintaining health and preventing disease. Using fecal metagenomic data from 1,177 individuals across three countries, we examine the relationship between diet and bacterial genera, focusing on Prevotella and Faecalibacterium, which have gained significant attention for their potential roles in human health and strong associations with dietary patterns. We find that these two genera in particular show significant associations with many aspects of diet but these associations vary in scale and direction, depending on the level of metagenomic resolution (i.e., genus level by reads and strain level by metagenome-assembled genomes) and the contextual population. These results highlight the growing importance of building metagenomic data sets that are standardized, comprehensive, and representative of diverse populations to increase our ability to tease apart the complex relationship between diet and the microbiome.<br><br>IMPORTANCE: An analysis of fecal microbiome data from individuals in the United States, United Kingdom, and Mexico shows that associations with dietary components vary both by country and by level of resolution (i.e., genus and strain). Our work sheds light on why there may be conflicting reports regarding microbial associations with diet, disease, and health.}, }
@article {pmid40586419, year = {2025}, author = {Dason, MS and Corà, D and Re, A}, title = {Sequence modeling tools to decode the biosynthetic diversity of the human microbiome.}, journal = {mSystems}, volume = {}, number = {}, pages = {e0033325}, doi = {10.1128/msystems.00333-25}, pmid = {40586419}, issn = {2379-5077}, abstract = {Understanding the biosynthetic potential of the human microbiome remains a significant challenge with far-reaching scientific and translational implications. Analyses of human-associated (meta)genomic sequencing data undeniably show that the biosynthetic diversity encoded in these genomes is largely underexplored. A crucial step in studying specialized metabolites involves the sequence-based identification of genes encoding biosynthetic pathways, typically organized into biosynthetic gene clusters (BGCs). In this review, we provide a concise and updated overview of the widening range of computational approaches that have effectively addressed the sequence-based identification of BGCs across both isolated genomes and complex microbial communities. These advancements are set to deepen our understanding of the biosynthetic potential and diversity of microorganisms residing in different human body sites.}, }
@article {pmid40585799, year = {2025}, author = {Alty, JW and Barnes, CE and Nicoli, AM and Turner, BS and Beneman, EA and Dugan, AE and Brucks, SD and Kruger, AG and Schrock, RR and Ribbeck, K and Kiessling, LL}, title = {Synthetic Mucins as Glycan-Defined Prebiotics.}, journal = {ACS central science}, volume = {11}, number = {6}, pages = {918-926}, pmid = {40585799}, issn = {2374-7943}, abstract = {The human microbiome contains at least as many bacterial cells as human cells. Some bacteria offer benefits, like improving gut barrier function, suppressing pathobiont growth, and modulating immunity. These benefits have popularized probiotics, but probiotic retention is often hindered by low colonization efficiency in the mucosal layer that lines all epithelial cells. Mucins, the primary components of mucus, are essential for the organization and regulation of microbial populations. The molecular mechanisms of mucin-probiotic interactions remain understudied due, in part, to the inability to incisively manipulate native mucin sequences or their glycans. Here, we used synthetic mucins with defined glycan presentations to interrogate glycan-dependent interactions between mucus and three probiotic lactobacilli species. The nutrient conditions under which bacteria were cultured influenced glycan binding preferences, suggesting mucin-probiotic interactions change with nutrient availability. The addition of synthetic mucins to native mucin increased Limosilactobacillus fermentum adherence. Additionally, an increase in glycosidase activity indicated that native and synthetic mucins function as prebiotics, as probiotic bacteria can cleave the displayed O-glycans. Thus, synthetic mucins can cultivate target probiotic bacteria and increase adhesion as binding sites, highlighting their value as tools for elucidating native mucin functions and as promising agents for promoting human health.}, }
@article {pmid40575486, year = {2025}, author = {Nieves, L and Roach, A and Hunter, J and Smeh, S and Islas, A and Islas, A and Blattman, J and Di Palma, M}, title = {Harnessing the microbiome to improve clinical outcomes for cancer, transplant, and immunocompromised patients in the intensive care unit (ICU).}, journal = {Frontiers in cellular and infection microbiology}, volume = {15}, number = {}, pages = {1577108}, pmid = {40575486}, issn = {2235-2988}, mesh = {Humans ; *Intensive Care Units ; *Neoplasms/microbiology/therapy/immunology ; *Immunocompromised Host ; *Microbiota ; Dysbiosis/microbiology ; *Transplant Recipients ; Treatment Outcome ; }, abstract = {In recent decades, there has been a growing emphasis on understanding how the architecture of the human microbiome can impact typical biological processes and patient clinical outcomes. In fact, microbiome modifications and modulations have not only been associated with impacts on general health and well-being but have also been shown to yield differences in patient responsiveness to vaccines, medications, and chemotherapeutic regimens. Much of this influence likely stems from how changes in the microbiome result in differences in microbial communities and the subsequent release of microbial-derived metabolites that can alter typical immunological processes. Understanding how microbial composition can impact patient responsiveness can be particularly important in the intensive care unit (ICU), where the efficacy of medications and treatments can result in negative patient outcomes if unsuccessful. Clinical scientists have further developed the concept of the pathobiome, a disease-promoting microbiome whose development can be associated with dysbiosis. Understanding how the microbiome and its associated components can impact patient responsiveness, especially in the ICU, must be further researched and understood. Here, we analyze what causes variances in the microbiome and pathobiome in significant immunocompromised populations, including cancer patients and transplant recipients, and how variances in the microbiome can impact patient outcomes in the ICU. Further, we detail potential future applications of how our understanding of what impacts the human microbiome during the treatment of these populations may be exploited to improve patient prognosis.}, }
@article {pmid40574683, year = {2025}, author = {}, title = {Correction to: Human microbiome: Impact of newly approved treatments on C. difficile infection.}, journal = {American journal of health-system pharmacy : AJHP : official journal of the American Society of Health-System Pharmacists}, volume = {}, number = {}, pages = {}, doi = {10.1093/ajhp/zxaf137}, pmid = {40574683}, issn = {1535-2900}, }
@article {pmid40572254, year = {2025}, author = {Park, Y and Kyung, S and Mun, S and Yu, BS and Yun, K and Baek, C and Lee, DG and Kang, S and Kim, SR and Kim, JH and Lee, Y and Park, BC and Han, K}, title = {Comparative Analysis of Bacteriome in Hair Follicle Layers of Patients with Female Pattern Androgenic Alopecia.}, journal = {Microorganisms}, volume = {13}, number = {6}, pages = {}, pmid = {40572254}, issn = {2076-2607}, abstract = {Androgenetic alopecia (AGA) is the most common form of patterned hair loss, exhibiting gender-specific clinical features. Recent studies highlight the importance of the skin microbiome in maintaining skin health, but the relationship between the hair follicle microbiome and hair loss, particularly AGA, remains understudied. Hair follicle layer samples were collected directly from the crown region of female pattern hair loss (FPHL), male pattern hair loss (MPHL), and healthy adult women (control) groups. Microbial DNA was extracted and analyzed using Illumina 16S rRNA V3-V4 gene amplicon sequencing. Alpha-diversity and beta-diversity analyses and taxonomic and functional profiling were conducted through relative abundance, LEfSe, and PICRUSt2 analyses. The alpha-diversity analysis showed a significant decrease in microbial richness in the hair loss groups. Unweighted UniFrac-based beta-diversity analysis revealed significant clustering between the control group and the FPHL group. Taxonomic profiling and LEfSe analysis identified differences in microbial composition and biomarkers. PICRUSt2 analysis further revealed altered pathways related to porphyrin metabolism, fatty acid biosynthesis, and steroid hormone metabolism. Additionally, differences in microbiome composition and potential functions were found between the FPHL and MPHL groups. This study provides comprehensive insights into the hair follicle microbiome, revealing unique microbial patterns and functional alterations associated with FPHL. Understanding these microbiome characteristics may contribute to targeted approaches for addressing AGA. Further research is warranted.}, }
@article {pmid40571109, year = {2025}, author = {Chen, H and Qiu, X and Lei, S and Zhao, Y and Zhang, M and Gao, M and Guo, R and Di, H and Huang, J and Yu, Z}, title = {Gut vs. Vaginal Microbiome in Diabetes Progression: Key Microbial Shifts and Implications.}, journal = {Microbial pathogenesis}, volume = {}, number = {}, pages = {107833}, doi = {10.1016/j.micpath.2025.107833}, pmid = {40571109}, issn = {1096-1208}, abstract = {BACKGROUND: Dysiosis in gut and vaginal microbiome is implicated in type 2 diabetes (T2D) pathogenesis, but their contributions remain unclear. This study aims to compare their alterations and clinical relevance in diabetes development.<br><br>METHODS: Metagenomic sequencing was performed on vaginal and fecal samples from T2D patients. Differential feature selection and correlation model were used to dissect microbial contributions to diabetic markers.<br><br>RESULTS: Gut microbiota exhibited reduced diversity in T2D patients, with enrichment of Desulfovibrio desulfuricans and Adlercreutzia equolifaciens validated in public cohorts. Vaginal microbiota diversity remained unaffected. Furthermore, structural equation modeling revealed stronger gut microbiota associations with blood glucose and HbA1c. Notably, Romboutsia ilealis-derived pgm was enriched in the diabetes group, which could catalyze the production of glucose, suggesting that it may be involved in the progression of T2D.<br><br>CONCLUSION: Our findings establish the gut microbiome as the dominant driver of T2D progression, with R. ilealis emerging as a potential therapeutic target. This highlights the priority of gut-centric microbiota interventions in diabetes management.}, }
@article {pmid40569694, year = {2025}, author = {Kasmanas, JC and Magnúsdóttir, S and Zhang, J and Smalla, K and Schloter, M and Stadler, PF and de Leon Ferreira de Carvalho, ACP and Rocha, U}, title = {Integrating comparative genomics and risk classification by assessing virulence, antimicrobial resistance, and plasmid spread in microbial communities with gSpreadComp.}, journal = {GigaScience}, volume = {14}, number = {}, pages = {}, doi = {10.1093/gigascience/giaf072}, pmid = {40569694}, issn = {2047-217X}, support = {2019/03,396-9//S&#xe3;o Paulo Research Foundation/ ; 2022/03,534-5//S&#xe3;o Paulo Research Foundation/ ; //Deutsche Forschungsgemeinschaft/ ; //International Development Research Centre/ ; }, mesh = {*Plasmids/genetics ; Humans ; *Genomics/methods ; Virulence/genetics ; *Drug Resistance, Bacterial/genetics ; Gastrointestinal Microbiome/genetics ; Virulence Factors/genetics ; Computational Biology/methods ; Software ; Genome, Bacterial ; *Bacteria/genetics/pathogenicity/drug effects ; }, abstract = {BACKGROUND: Comparative genomics, genetic spread analysis, and context-aware ranking are crucial in understanding microbial dynamics' impact on public health. gSpreadComp streamlines the path from in silico analysis to hypothesis generation. By integrating comparative genomics, genome annotation, normalization, plasmid-mediated gene transfer, and microbial resistance-virulence risk-ranking into a unified workflow, gSpreadComp facilitates hypothesis generation from complex microbial datasets.<br><br>FINDINGS: The gSpreadComp workflow works through 6 modular steps: taxonomy assignment, genome quality estimation, antimicrobial resistance (AMR) gene annotation, plasmid/chromosome classification, virulence factor annotation, and downstream analysis. Our workflow calculates gene spread using normalized weighted average prevalence and ranks potential resistance-virulence risk by integrating microbial resistance, virulence, and plasmid transmissibility data and producing an HTML report. As a use case, we analyzed 3,566 metagenome-assembled genomes recovered from human gut microbiomes across diets. Our findings indicated consistent AMR across diets, with diet-specific resistance patterns, such as increased bacitracin in vegans and tetracycline in omnivores. Notably, ketogenic diets showed a slightly higher resistance-virulence rank, while vegan and vegetarian diets encompassed more plasmid-mediated gene transfer.<br><br>CONCLUSIONS: The gSpreadComp workflow aims to facilitate hypothesis generation for targeted experimental validations by the identification of concerning resistant hotspots in complex microbial datasets. Our study raises attention to a more thorough study of the critical role of diet in microbial community dynamics and the spread of AMR. This research underscores the importance of integrating genomic data into public health strategies to combat AMR. The gSpreadComp workflow is available at https://github.com/mdsufz/gSpreadComp/.}, }
@article {pmid40568731, year = {2025}, author = {Masetti, R and Barbara, G and Muratore, E and Marasco, G and Cremon, C and Marangoni, A and Brigidi, P and Putignani, L and Angelino, G and Quagliarella, F and Galaverna, F and Leardini, D and Lazzarotto, T and Gabelli, M and Savarino, E and Zecca, M and Faraci, M and Prete, A and Biffi, A and Locatelli, F and Merli, P}, title = {Fecal microbiota transplantation for decolonization from multidrug-resistant bacteria in pediatric allogeneic hematopoietic stem cell transplantation recipients: a retrospective real-word data study.}, journal = {Haematologica}, volume = {}, number = {}, pages = {}, doi = {10.3324/haematol.2025.288067}, pmid = {40568731}, issn = {1592-8721}, abstract = {Not available.}, }
@article {pmid40566568, year = {2025}, author = {Papakonstantinou, A and Moustakli, E and Potiris, A and Zikopoulos, A and Tsarna, E and Christodoulaki, C and Tsakiridis, I and Dagklis, T and Panagopoulos, P and Drakakis, P and Stavros, S}, title = {Behind-the-Scenes Actors in Fertility: A Comprehensive Review of the Female Reproductive Tract Microbiome and Its Clinical Relevance.}, journal = {Life (Basel, Switzerland)}, volume = {15}, number = {6}, pages = {}, doi = {10.3390/life15060916}, pmid = {40566568}, issn = {2075-1729}, abstract = {The study of the microbiome has rapidly progressed over the past few decades, capturing the interest of both scientists and the general public. Nevertheless, there is still no widely agreed-upon definition for the term "microbiome" despite tremendous advances in our knowledge. The international scientific literature consistently underscores the difference between the human microbiome and human microbiota. Recent research has emphasized the importance of the female reproductive tract microbiome in fertility, impacting natural conception and assisted reproductive technologies (ARTs). This review explores the relationship between infertility and the microbiota of the female reproductive tract through a thorough evaluation of research papers and large-scale studies published up to 2024. The objective of this review is to critically assess current evidence on the role of the reproductive tract microbiome in female infertility and ART outcomes. Relevant papers were identified and analyzed through the electronic medical databases PubMed/MEDLINE and Scopus. A comprehensive synthesis of data from 36 original studies was performed, including observational, case-control, cohort, and randomized trials. By focusing on the vagina, cervix, and endometrium, this study offers a comprehensive overview of the microbiome throughout the female reproductive tract. RIF and poor reproductive outcomes are strongly linked to dysbiosis, which is characterized by a reduction in Lactobacillus species. Lactobacillus crispatus, in particular, plays a significant role in protecting against bacterial vaginosis and infertility. A thorough understanding of how the microbiome impacts fertility and the development of clinical strategies to improve reproductive outcomes requires standardized microbiome investigation techniques and larger, randomized trials that account for diverse patient characteristics.}, }
@article {pmid40562845, year = {2025}, author = {Shiner, YA and Caplan, S and Doweck, I}, title = {Actinomyces findings in tonsillectomy specimens- comparison between adults and pediatrics populations.}, journal = {European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery}, volume = {}, number = {}, pages = {}, pmid = {40562845}, issn = {1434-4726}, abstract = {BACKGROUND: Tonsillectomy is a common surgical procedure primarily performed for obstructive sleep apnea (OSA) and recurrent acute tonsillitis. Actinomyces are gram-positive, anaerobic bacteria commonly found in the oral cavity and known to form part of the human microbiome, occasionally associated with localized infections. While Actinomyces bacterial colonization in tonsils has been previously studied, its correlation with surgical indications and outcomes remains unclear.<br><br>OBJECTIVES: The study aimed to investigate the relationship between Actinomyces colonization in tonsillar specimens and surgical indications, and to examine whether Actinomyces presence influences tonsillectomy outcomes, specifically post-operative hemorrhage and hospital stay.<br><br>METHODS: This retrospective cohort study analyzed electronic medical records from Lady Davis Carmel Medical Centre between 2011 and 2021. The study included 1,333 patients who underwent extra-capsular tonsillectomies. Patient demographics, surgical indications, length of hospital stay, post-surgical complications, and pathological reports were collected and analyzed using IBM SPSS Statistics 28.0.<br><br>RESULTS: The study population consisted of 760 (57%) males and 573 (43%) females, with an age range of 0.98 to 67.5&#xa0;years (mean 9.1&#xa0;years). Actinomyces was present in 13.2% of specimens from patients with infectious indications compared to 4.5% in patients with obstructive indications (p&#x2009;<&#x2009;0.001). A statistically significant age difference was observed between patients with (17.78&#xa0;years) and without (8.55&#xa0;years) Actinomyces. Multivariate analysis revealed that age was the most significant predictor of Actinomyces presence (OR 1.047, p&#x2009;<&#x2009;0.0001).<br><br>CONCLUSIONS: The study found a significant correlation between Actinomyces presence, older age, and infectious surgical indications. While Actinomyces colonization did not demonstrate a direct influence on surgical complications, the findings suggest potential clinical relevance that merits further research to elucidate the bacterium's role in tonsillar pathology.}, }
@article {pmid40560509, year = {2025}, author = {Andersen, C and Ebsen, TS and Thorup, CA and Reinholdt, KB and Kjaerulff, AMG and Udholm, N and Khalid, V and Madzak, A and Duez, C and Münch, H and Pauli, S and Danstrup, CS and Petersen, NK and Greve, T and Klug, TE}, title = {Next-generation sequencing of the tonsillar microbiome in severe acute tonsillitis: comparison with healthy controls and culture-based findings.}, journal = {European journal of clinical microbiology &amp; infectious diseases : official publication of the European Society of Clinical Microbiology}, volume = {}, number = {}, pages = {}, pmid = {40560509}, issn = {1435-4373}, abstract = {PURPOSE: Previous culture-based studies suggest three significant pathogens in acute tonsillitis (AT): Streptococcus pyogenes, Fusobacterium necrophorum, and Streptococcus dysgalactiae. Next-generation sequencing (NGS) provides further insights into the human microbiome and may pinpoint additional pathogens in bacterial infections. We aimed to investigate the tonsillar microbiome and identify pathogens associated with AT by applying NGS to tonsillar swabs from patients with severe AT, comparing the findings with both healthy controls and culture-based results.<br><br>METHODS: Full-length sequencing of the 16S rRNA gene (16S tNGS) was performed on tonsillar swabs from 64 AT patients and 55 controls, who were prospectively enrolled at two Danish Ear-Nose-Throat Departments between June 2016 and December 2019.<br><br>RESULTS: The mean number of detected bacteria was significantly higher in patients analysed with 16S tNGS (36) than with culture methods (6.5, p&#x2009;<&#x2009;0.001). The alpha diversity was lower in patients compared to controls (p&#x2009;<&#x2009;0.001) and beta diversity showed separation of the two groups (p&#x2009;=&#x2009;0.001). S. pyogenes (p&#x2009;=&#x2009;0.001) and Bifidobacteriaceae (p&#x2009;=&#x2009;0.002) were significantly more abundant in patients compared to controls. The three suggested pathogens were detected more frequently using 16S tNGS compared to culture: S. pyogenes (38% vs. 27%, p&#x2009;=&#x2009;0.26), F. necrophorum (19% vs. 11%, p&#x2009;=&#x2009;0.32), and S. dysgalactiae (14% vs. 11%, p&#x2009;=&#x2009;0.79).<br><br>CONCLUSION: The tonsillar microbiome differed significantly between AT patients and healthy controls. Our findings confirm the role of S. pyogenes in AT, but did not identify additional likely pathogens. The addition of 16S tNGS to cultures increased the collective detection rate of three previously suggested pathogens from 48 to 70%.}, }
@article {pmid40550997, year = {2025}, author = {Zhang, Y and Ke, S and Wang, XW and Sun, Y and Weiss, ST and Liu, YY}, title = {Association rule mining of the human gut microbiome.}, journal = {Science China. Life sciences}, volume = {}, number = {}, pages = {}, pmid = {40550997}, issn = {1869-1889}, abstract = {The human gut carries a vast and diverse microbial community that is essential for human health. Understanding the structure of this complex community is a crucial step toward comprehending human-microbiome interactions. Traditional co-occurrence and correlation analyses typically focus on pairwise relationships and ignore higher-order relationships. Association rule mining (ARM) is a well-developed technique in data mining and has been applied to human microbiome data to identify higher-order relationships. Yet, existing attempts suffer from small sample sizes and low taxonomic resolution. We developed an advanced ARM framework and systematically investigated the interactions between microbial species using a public large-scale uniformly processed human microbiome data from the curatedMetagenomicData (CMD) together with ARM. First, we inferred association rules in the gut microbiome samples of healthy individuals (n=2,815) in CMD. Then we compared those rules with those inferred from the individuals with different diseases: inflammatory bowel disease (IBD, n=768), colorectal cancer (CRC, n=368), impaired glucose tolerance (IGT, n=199), and type 2 diabetes (T2D, n=164). Finally, we demonstrated that ARM is an efficient feature selection tool that can improve the performance of microbiome-based disease classification. Together, this study illustrates the higher-order microbial relationships in the human gut microbiome and highlights the critical importance of incorporating association rules in microbiome-based disease classification.}, }
@article {pmid40550653, year = {2025}, author = {Lai, P and He, Z}, title = {[Probiotics empower postoperative intestinal function recovery after colorectal surgery: mechanisms and clinical progress].}, journal = {Zhonghua wei chang wai ke za zhi = Chinese journal of gastrointestinal surgery}, volume = {28}, number = {6}, pages = {619-626}, doi = {10.3760/cma.j.cn441530-20250310-00093}, pmid = {40550653}, issn = {1671-0274}, mesh = {Humans ; Gastrointestinal Microbiome ; *Probiotics/therapeutic use ; Recovery of Function ; *Colorectal Surgery ; Dysbiosis ; *Intestines/microbiology ; Postoperative Period ; Postoperative Complications/prevention &amp; control ; }, abstract = {Gastrointestinal dysfunction is a common and significant complication in colorectal surgical practice, which is associated with gut microbiota dysbiosis caused by various perioperative interventions. Currently, enhanced recovery after surgery (ERAS) protocols have been increasingly adopted in clinical practice, greatly accelerating the recovery of postoperative intestinal function. However, there are still no effective interventions in the ERAS protocols to target surgery-induced gut microbiota dysbiosis. Probiotics, as a key treatment method targeting the gut microbiota, can stimulate intestinal motility, inhibit the colonization of pathogenic bacteria, enhance intestinal barrier function, among other effects. Based on these effects of probiotics, they are expected to resolve the neglected gut microbiota dysbiosis, further accelerating the postoperative recovery of intestinal function after colorectal surgery. This article reviews the mechanisms and clinical progress in postoperative bowel functional recovery after colorectal surgery.}, }
@article {pmid40546285, year = {2025}, author = {Pei, X and Liu, M and Yu, S}, title = {How is the human microbiome linked to kidney stones?.}, journal = {Frontiers in cellular and infection microbiology}, volume = {15}, number = {}, pages = {1602413}, doi = {10.3389/fcimb.2025.1602413}, pmid = {40546285}, issn = {2235-2988}, abstract = {In recent years, the incidence of kidney stones has continued to rise worldwide, and conventional treatments have limited efficacy in treating stones associated with recurrent or metabolic abnormalities. The microbiome, as the 'second genome' of the host, is involved in the development of kidney stones through metabolic regulation, immune homeostasis and inflammatory response. Studies have shown that the urinary microbiome of healthy people is dominated by commensal bacteria such as Lactobacillus and Streptococcus, which maintain microenvironmental homeostasis, whereas patients with renal stones have a significantly reduced diversity of intestinal and urinary microbiomes, with a reduced abundance of oxalic acid-degrading bacteria (e.g., Bifidobacterium oxalicum, Bifidobacterium bifidum), and a possible concentration of pathogenic bacteria (e.g., Proteus mirabilis). The microbiome regulates stone formation through mechanisms such as metabolites (e.g., short-chain fatty acids), changes in urine physicochemical properties (e.g., elevated pH), and imbalances in the inflammatory and immune microenvironments. For example, urease-producing bacteria promote magnesium ammonium phosphate stone formation through the breakdown of urea, whereas dysbiosis of the intestinal flora increases urinary oxalic acid excretion and exacerbates the risk of calcium oxalate stones. Microbiome-based diagnostic markers (e.g., elevated abundance of Aspergillus phylum) and targeted intervention strategies (e.g., probiotic supplementation, faecal bacteria transplantation) show potential for clinical application. However, technical bottlenecks (e.g., sequencing bias in low-biomass samples), mechanistic complexity (e.g., multistrain synergism), and individual heterogeneity remain major challenges for future research. Integration of multi-omics data, development of personalised therapies and interdisciplinary research will be the core directions to decipher the relationship between microbiome and kidney stones.}, }
@article {pmid40538714, year = {2025}, author = {Guan, Z and Wang, H and Feng, Q}, title = {Establishment and improvement of genetic manipulation tools for Fusobacterium nucleatum.}, journal = {Engineering microbiology}, volume = {5}, number = {1}, pages = {100192}, pmid = {40538714}, issn = {2667-3703}, abstract = {An imbalance in oral microbial homeostasis is significantly associated with the onset and progression of several systemic diseases. Fusobacterium nucleatum, a ubiquitous periodontitis-causing bacterium in the oral cavity, is frequently detected in focal sites and contributes to the pathogenesis of many extraoral diseases, including cancers, cardiovascular diseases, and adverse pregnancy outcomes (APOs). F. nucleatum is one of the few oral anaerobes that can be cultured purely in vitro and is a 'model species' for studying the impact of oral health on systemic health. The establishment and development of genetic manipulation tools for F. nucleatum and the construction of pathogenic gene-disrupted strains are important strategies for studying the pathogenicity of F. nucleatum. Here, we review the establishment and development of the genetic manipulation systems for F. nucleatum and summarize the characteristics of various genetic manipulation tools, such as suicide plasmid-based systems for gene inactivation, replicable plasmid-based systems controlling gene expression, and transposon-based random mutagenesis systems. Notably, we summarize and analyze their applications in the study of the pathogenic mechanisms of F. nucleatum. We hope to provide reference information and ideas for future research on genetic manipulation tools and the pathogenic mechanisms of F. nucleatum and other Fusobacterium species.}, }
@article {pmid40527211, year = {2025}, author = {Ghosh, S and Nath, S and Chakraborty, A and Bhowmick, S and Majumdar, KK and Mukherjee, S and Pramanik, S}, title = {Long-term arsenic exposure perturbs gut microbial diversity, composition and predicts metabolic dysregulation.}, journal = {Journal of hazardous materials}, volume = {495}, number = {}, pages = {138836}, doi = {10.1016/j.jhazmat.2025.138836}, pmid = {40527211}, issn = {1873-3336}, abstract = {The present study documents significant alterations in human gut microbial composition in arsenic exposed populations of West Bengal, India through amplicon sequencing of human stool metagenomic DNA. A notable reduction in α-diversity underscored a reduced species richness and an altered predominance. β- diversity analysis revealed prominent inter-individual differences. Among the 26 phyla detected, significant perturbation was noted in Bacteroidetes, Actinobacteria, Proteobacteria, and Firmicutes. Species analysis identified significant increase in Bifidobacterium adolescentis, B.longum, Blautia luti, B.wexlerae, Clostridium saudiense, Romboutsia timonensis and Streptococcus salivarius whereas members of Faecalibacterium prausnitzii, Megasphaera elsdenii, Prevotella copri and P. stercorea were found to be highly diminished due to As stress. PICRUSt analysis predicted significant upregulation (pT-test< 0.05) in gene families associated with carbohydrate, amino acid, nucleotide and lipid metabolism along with fermentation and secondary metabolite/ vitamin synthesis pathways in exposed group confirmed through Linear Discriminant Analysis. B.longum, B.luti and S.salivarius were found to be associated with obesity and ulcerative colitis. Network interactions were also characterized with major disruptions in keystone species interaction. The major findings of this study shall drive future studies like community-based metagenomics, metabolomics and in-vitro microbial verifications for designing of microbial therapeutics targeting gut health to combat the harmful impact of As exposure.}, }
@article {pmid40526755, year = {2025}, author = {Zheng, Q and Zhong, Y and Lian, H and Zhuang, J and Wang, L and Chen, J and Wang, H and Wang, H and Ye, X and Huang, Z and Yang, K}, title = {Gut Microbial Signatures Associated With Clinical Remission in Inflammatory Bowel Disease Treated With Biologics: A Comprehensive Multi-Cohort Analysis.}, journal = {United European gastroenterology journal}, volume = {}, number = {}, pages = {}, doi = {10.1002/ueg2.70064}, pmid = {40526755}, issn = {2050-6414}, support = {No. 82300619//National Natural Science Foundation of China/ ; 2023A04J2245//Science and Technology Project in Guangzhou/ ; No. 20231800936102//Dongguan Science and Technology of Social Development Program/ ; No. 2022E02125//Science and Technology Aid Project of Xinjiang Uygur Autonomous Region/ ; }, abstract = {BACKGROUND AND AIMS: The relationship between gut microbiota and biological treatment response in inflammatory bowel disease (IBD) remains incompletely understood. We sought to characterize microbial signatures associated with clinical remission and develop a prediction model for clinical remission.<br><br>METHODS: We analyzed 16&#xa0;S rRNA gene sequencing data from two independent public cohorts (n&#xa0;=&#xa0;231) treated with biologics (infliximab: n&#xa0;=&#xa0;23; adalimumab: n&#xa0;=&#xa0;22; ustekinumab: n&#xa0;=&#xa0;186). Microbial diversity and taxonomic compositions were compared between the remission and non-remission groups. Random Forest algorithm was employed to construct a prediction model using differential genera and clinical features, with performance evaluated through cross-validation. The model was further validated in a local cohort (n&#xa0;=&#xa0;29).<br><br>RESULTS: Significant differences in alpha and beta diversity were observed between the remission and non-remission groups (p&#xa0;<&#xa0;0.05). MaAsLin2 analysis identified 25 differentially abundant genera (p&#xa0;<&#xa0;0.05). Among these, we selected the top 10 genera with highest importance scores (Parabacteroides_B_862066, Agathobaculum, Ruminococcus_E, Sutterella, Clostridium_R_135822, Hominilimicola, Onthenecus, Butyricimonas, Bariatricus, Hominenteromicrobium) to build the Random Forest model, notably all enriched in remission patients. The model demonstrated robust predictive performance for clinical remission (AUC: 0.895), which was further validated in the local cohort (AUC: 0.750).<br><br>CONCLUSION: There is a relationship between gut microbial signatures and biological treatment outcomes in IBD patients. A predictive model based on gut microbiota composition may help stratify patients for treatment response. Further investigation of microbiome modulation strategies may enhance therapeutic efficacy.}, }
@article {pmid40524314, year = {2025}, author = {Schumacher, J and Müller, P and Sulzer, J and Faber, F and Molitor, B and Maier, L}, title = {Proton-pump inhibitors increase C. difficile infection risk by altering pH rather than by affecting the gut microbiome based on a bioreactor model.}, journal = {Gut microbes}, volume = {17}, number = {1}, pages = {2519697}, doi = {10.1080/19490976.2025.2519697}, pmid = {40524314}, issn = {1949-0984}, mesh = {*Proton Pump Inhibitors/adverse effects/pharmacology ; *Gastrointestinal Microbiome/drug effects ; Humans ; Hydrogen-Ion Concentration ; *Clostridioides difficile/drug effects/growth &amp; development ; Omeprazole/pharmacology/adverse effects ; *Clostridium Infections/microbiology ; Bioreactors/microbiology ; Bacteria/drug effects/classification/genetics/growth &amp; development/isolation &amp; purification ; Feces/microbiology ; }, abstract = {Clostridioides difficile infections often occur after antibiotic use, but they have also been linked to proton-pump inhibitor (PPI) therapy. The underlying mechanism - whether infection risk is due to a direct effect of PPIs on the gut microbiome or changes in gastrointestinal pH - has remained unclear. To disentangle both possibilities, we studied the impact of the proton-pump inhibitor omeprazole and pH changes on key members of the human gut microbiome and stool-derived microbial communities from different donors in vitro. We then developed a custom multiple-bioreactor system to grow a model human microbiome community and a stool-derived community in chemostat mode and tested the effects of omeprazole exposure, pH changes, and their combination on C. difficile growth within these communities. Our findings show that changes in pH significantly affect the gut microbial community's biomass and the abundances of different bacterial taxa, leading to increased C. difficile growth within the community. However, omeprazole treatment alone did not result in such effects. These findings imply that the higher risk of C. difficile infection following proton-pump inhibitor therapy is probably because of alterations in gastrointestinal pH rather than a direct interaction between the drug and the microbiome. This understanding offers a new perspective on infection risks in proton-pump inhibitor therapy.}, }
@article {pmid40524025, year = {2025}, author = {Mallari, P and Rostami, LD and Alanko, I and Howaili, F and Ran, M and Bansal, KK and Rosenholm, JM and Salo-Ahen, OMH}, title = {The Next Frontier: Unveiling Novel Approaches for Combating Multidrug-Resistant Bacteria.}, journal = {Pharmaceutical research}, volume = {}, number = {}, pages = {}, pmid = {40524025}, issn = {1573-904X}, support = {190913//Svenska Kulturfonden/ ; 188147//Svenska Kulturfonden/ ; }, abstract = {BACKGROUND: The rapid occurrence of bacterial antibiotic resistance poses a significant threat to public health worldwide. Since particularly multidrug-resistant (MDR) pathogens are becoming untreatable with currently available antibiotics, new treatment modalities must be deployed.<br><br>OBJECTIVES: This review explores the recent advancements and the enduring challenges in new antibacterial&#xa0;development for drug-resistant organisms.<br><br>RESULTS: We describe how bacterial resistance to antibiotics arises and discuss why the traditional drug discovery&#xa0;routes are inefficient. The best alternative strategies to overcome these challenges might include exploring new&#xa0;bacterial pathways, utilizing compounds with antibacterial activities from the human microbiome, and repurposing&#xa0;existing drugs. Moreover, novel drug delivery mechanisms that leverage, for example, nanotechnology-based&#xa0;carriers may be breakthrough ideas that can increase antibiotic efficacy and, at the same time, reduce toxicity.&#xa0;Current clinical trials of next-generation drugs indicate that some treatments possess excellent potential to&#xa0;overcome the MDR issue.<br><br>CONCLUSION: Despite the substantial obstacles to getting bench findings to the patient, numerous scientists are still&#xa0;working towards this goal. Both the application of antibiotic stewardship principles and timely considerations through&#xa0;the regulatory pathways are needed to release the next generation of antibiotics that are suitable for the fight&#xa0;against superbugs.}, }
@article {pmid40520768, year = {2025}, author = {Feng, Z and Burgermeister, E and Philips, A and Zuo, T and Wen, W}, title = {The gut virome in association with the bacteriome in gastrointestinal diseases and beyond: roles, mechanisms, and clinical applications.}, journal = {Precision clinical medicine}, volume = {8}, number = {2}, pages = {pbaf010}, pmid = {40520768}, issn = {2516-1571}, abstract = {The gut virome, an essential component of the intestinal microbiome, constitutes ∼0.1% of the total microbial biomass but contains a far greater number of particles than bacteria, with phages making up 90%-95% of this virome. This review systematically examines the developmental patterns of the gut virome, focusing on factors influencing its composition, including diet, environment, host genetics, and immunity. Additionally, it explores the gut virome's associations with various diseases, its interactions with gut bacteria and the immune system, and its emerging clinical applications.}, }
@article {pmid40520523, year = {2025}, author = {Zaki, EA and Afifi, SM and Ammar, NM and Kadry, MO}, title = {Assembled human microbiome and metabolome in chronic kidney disease: Dysbiosis a double-edged sword interlinking Circ-YAP1, Circ-APOE &amp; Circ-SLC8A1.}, journal = {Toxicology reports}, volume = {14}, number = {}, pages = {102058}, pmid = {40520523}, issn = {2214-7500}, abstract = {Dysbiosis is an alteration in microbiota diversity previously elucidated in patients with chronic kidney disease (CKD). Relationship between dysbiosis and CKD is bidirectional; Uremic milieu disturbs the human microbiota on the other hand, gut metabolites influence CKD development. As a result, we outline the possible contribution of microbiota in the pathophysiology, diagnosis and monitoring of CKD. A growing body of research indicates that changes in circular RNAs (circ-RNAs) were observed in CKD with pathogenic implications, including modifying intracellular signaling, exaggerating oxidative stress, cellular apoptosis and inflammation. Additionally, Circ-RNAs exhibit promising role in clinical settings for monitoring, diagnosis, prognostication, and treatment of CKD. Herein blood samples were collected from 60 Egyptian patients with CKD as well as 60 healthy volunteers who served as controls. Following clinical evaluations, OPLS-DA and PCA GC-MS analysis were performed to detect metabolite perturbations. The levels of toxic uremic metabolites, such as urea, hexanedioic acid, ribonic acid, dodecanoic acid, pyrimidine, 1H-indole, 1H-indole-3-acetic acid, butanoic acid, L-cystine, and benzaldehyde linked to renal fibrosis were found to be elevated. Conversely, Reno-protective metabolites, such as short-chain fatty acids; 1H-indole were found to be negatively correlated with indole propionic acid, acetic acid, 2-propenoic acid, tryptophan, tyrosine, and glucitol (AUC 0.65) derived from the gut flora. CKD patients clarified an alteration both gene and protein expression of circRNAs (Circ-YAP1, circ-APOE, and circ-SLC8A1)/mTOR. Moreover, these biomarkers had a significant correlation with clinical investigations such as Creatinine, Glomerular filtration rate (GFR) and albumin/Creatinine (A/C) ratio. These results shed some light on the metabolic biomarkers that are associated with CKD and novel insights into metabolomics/microbiota/Circ-YAP1/circ-APOE/circ-SLC8A1/mTOR interlinked with disease prognosis/diagnosis that could be translated into clinically relevance.}, }
@article {pmid40517367, year = {2025}, author = {Xi, S and Lin, T and Haiyan, Z and Shiyue, Z and Qi, Q and Qiangqiang, X and Mingzhi, Z and Liu, L}, title = {Propionate ameliorates neural degeneration by modulating mitochondrial fission and fusion in nerve cells.}, journal = {Neurological research}, volume = {}, number = {}, pages = {1-10}, doi = {10.1080/01616412.2025.2520019}, pmid = {40517367}, issn = {1743-1328}, abstract = {BACKGROUND: Sporadic global cognitive decline is on the rise, and current drugs exhibit limited efficacy. Propionate, an SCFAs of the human microbiome, exhibits robust neuroprotective effects.<br><br>METHODS: We used CCK8 to evaluate neuronal proliferation, DCFH-DA fluorescence probe to quantify ROS production, ELISA to detect IL-1&#x3b2; and IL-6 release, MitoTracker to assess mitochondrial membrane potential, real-time quantitative PCR, and western blotting to analyze DRP1 and anti-Mfn2 protein expression. We also established an in vitro blood-brain barrier model and AD mouse model.<br><br>RESULTS: Propionate normalized the mitochondrial membrane potential in glutamate-treated HT22 cells, reversed growth suppression, ROS accumulation, and elevated IL-1 and IL-6 release. Propionate also decreases Drp1 expression and elevates Mfn2 expression via GRP41 receptor binding. In vitro blood-brain barrier models illustrated the potential of propionate to ameliorate glutamate-induced blood-brain barrier damage. In vivo, propionate notably improved the learning and memory capabilities of AD mice and mitigated AD-induced mitochondrial defects.<br><br>CONCLUSION: Supplementation with propionate provides neuroprotection against neurodegenerative diseases. Propionate supplementation may provide a novel strategy for early intervention of neurological disorders.}, }
@article {pmid40507344, year = {2025}, author = {Gomes de Sousa, R and Guerreiro, CS and Santos, I and Cravo, M}, title = {The Knowledge Gap in Gut Microbiome Characterization in Early-Onset Colorectal Cancer Patients: A Systematic Scoping Review.}, journal = {Cancers}, volume = {17}, number = {11}, pages = {}, doi = {10.3390/cancers17111863}, pmid = {40507344}, issn = {2072-6694}, abstract = {BACKGROUND/OBJECTIVES: Over the past two decades, the incidence of early-onset colorectal cancer (EoCRC) has been increasing, although its underlying causes remain unclear. Gut microbiome is known to play a role in carcinogenesis of colorectal cancer. This scoping review aims to systematically map and synthetize current evidence on gut microbiome characterization in EoCRC (vs. late-onset colorectal cancer (LoCRC) and healthy individuals), describe the methodology used, and identify knowledge gaps to inform and guide future research.<br><br>METHODS: This systematic scoping review followed the Joanna Briggs Institute (JBI) methodology for scoping reviews. Searches were conducted in PubMed, Web of Science, and Scopus between January and February 2025. Two reviewers independently screened and selected the studies. One reviewer extracted the relevant information, using an adapted version of the JBI template.<br><br>RESULTS: Seven studies met eligibility criteria. Compared to healthy young adults, EoCRC patients had a predominance of lower &#x3b1; diversity, different &#x3b2; diversity, and greater abundance of Flavonifractor plautii, Akkermansia muciniphila, Bacteroides, and Fusobacteria. Comparisons with LoCRC showed that EoCRC had distinct &#x3b2; diversity and a higher abundance in Fusobacterium, Akkermansia, Bacteroides, and Actinomyces. Only three studies correlated the microbiota composition of EoCRC with clinicopathology features and suggested positive associations between Fusobacterium abundance, rectal tumors and lower survival and Akkermansia abundance with body mass index (BMI) &#x2265; 25 kg/m[2], rectal EoCRC, and better survival.<br><br>CONCLUSIONS: There is a lack of large, methodologically robust studies linking gut microbiota with clinicopathological, lifestyle, and tumor molecular features in EoCRC. Our review highlights critical knowledge gaps, the need for standardized methodologies, and key areas for future investigation.}, }
@article {pmid40505619, year = {2025}, author = {Bakkeren, E and Piskovsky, V and Foster, KR}, title = {Metabolic ecology of microbiomes: Nutrient competition, host benefits, and community engineering.}, journal = {Cell host &amp; microbe}, volume = {33}, number = {6}, pages = {790-807}, doi = {10.1016/j.chom.2025.05.013}, pmid = {40505619}, issn = {1934-6069}, mesh = {*Microbiota/physiology ; Humans ; *Nutrients/metabolism ; Animals ; *Bacteria/metabolism/genetics ; *Host Microbial Interactions ; Plants/microbiology ; }, abstract = {Many plants and animals, including humans, host diverse communities of microbes that provide many benefits. A key challenge in understanding microbiomes is that the species composition often differs among individuals, which can thwart generalization. Here, we argue that the key to identifying general principles for microbiome science lies in microbial metabolism. In the human microbiome and in other systems, every microbial species must find ways to harvest nutrients to thrive. The available nutrients in a microbiome interact with microbial metabolism to define which species have the potential to persist in a host. The resulting nutrient competition shapes other mechanisms, including bacterial warfare and cross-feeding, to define microbiome composition and properties. We discuss impacts on ecological stability, colonization resistance, nutrient provision for the host, and evolution. A focus on the metabolic ecology of microbiomes offers a powerful way to understand and engineer microbiomes in health, agriculture, and the environment.}, }
@article {pmid40501963, year = {2025}, author = {Chouhan, D and Grossman, AS and Kerns, KA and Stocke, KS and Kim, M and Dong, PT and Kumar, A and Lei, L and Lamont, RJ and McLean, JS and He, X and Bor, B}, title = {Episymbiotic Saccharibacteria suppresses epithelial immunoactivation through Type IV pili and TLR2 dependent endocytosis.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2025.05.30.656655}, pmid = {40501963}, issn = {2692-8205}, abstract = {Saccharibacteria are episymbionts that require host-bacteria to grow. They are positively associated with inflammatory diseases within the human microbiome, yet their mechanisms for interacting with the human host and contributing to diseases remain unknown. This study investigated interactions between a Saccharibacterium (Nanosynbacter lyticus), its host-bacteria (Schaalia odontolytica), and oral epithelial cells. The host-bacteria induced proinflammatory cytokines in epithelial cells, while Saccharibacteria were immune silent. Remarkably, Saccharibacteria dampened cytokine responses to host-bacteria during coinfection. This effect was driven by Saccharibacteria-induced clustering of TLR2 receptors, a process likely facilitated by type IV, ultimately leading to reduced TLR2-mediated cytokine signalling. High resolution imaging showed that Saccharibacteria were endocytosed by oral epithelial cells, and colocalized with endosome markers, eventually trafficking to lysosomes. Moreover, a subset of the Saccharibacteria survive endocytosis long-term, and retains their capability to reinfect host-bacteria, highlighting a mechanism for persistence in the oral microbiome and a vital role in mammalian immune system modulation.}, }
@article {pmid40498317, year = {2025}, author = {Viets, C and Stevens, CA}, title = {Measuring and Analyzing Bacterial Movement in Mucus.}, journal = {Methods in molecular biology (Clifton, N.J.)}, volume = {2942}, number = {}, pages = {187-197}, pmid = {40498317}, issn = {1940-6029}, mesh = {Humans ; *Mucus/microbiology/metabolism ; Mucins/metabolism ; *Time-Lapse Imaging/methods ; *Bacteria ; Microbiota ; }, abstract = {Humans are colonized by trillions of microbes that compose the human microbiome. Much of the microbiome inhabits the mucus layers. Mucus layers, covering digestive, reproductive, ocular, and respiratory tracts, are viscous networks consisting mainly of water and mucin glycoproteins. Mucins assemble into a dense, cross-linked network that can affect bacterial swimming patterns, and studying this behavior provides valuable insights into how the body regulates interactions with both harmful and beneficial microbes. Here we present the use of time-lapse imaging to track individual bacterial cells within mucin and discuss techniques for accurately extracting cell trajectory data from these images. By integrating theoretical and experimental approaches, we also describe how to quantify bacterial movement in terms of speed, persistence, and randomness.}, }
@article {pmid40492849, year = {2025}, author = {Coccolini, F and Kirkpatrick, AW and Cremonini, C and Sartelli, M}, title = {Source control in intra-abdominal infections: What you need to know.}, journal = {The journal of trauma and acute care surgery}, volume = {}, number = {}, pages = {}, doi = {10.1097/TA.0000000000004654}, pmid = {40492849}, issn = {2163-0763}, abstract = {Providing optimal source control (SC) for intra-abdominal sepsis (IAS) is a critically important surgical principle, yet one that remains nebulous in terms of strict definitions and required conduct. The entire concept of SC has evolved in the last decades. Contemporary SC is not only surgical but also embraces minimally invasive percutaneous and medical therapies. We propose that adequate SC has evolved from the mere anatomical control of enteric leakage, cleansing of obvious contaminants and necrosis, to a more comprehensive anatomo-phyiological-biochemical model. While any breaches in the integrity of the gastrointestinal tract should be addressed urgently, SC should ultimately aim to control the generation and propagation of systemic biomediators, bacterial toxins, and toxic catabolites that perpetuate multisystem organ failure and death. Much urgently needs to be learned to understand and hopefully mitigate the dysbiotic influences of IAS on the human microbiome. Finally, the therapy offered should always be individualized, recognizing patient's unique pathophysiology, clinical condition, comorbidities, and predeclared preferences regarding invasive therapies and life-support.}, }
@article {pmid40491241, year = {2025}, author = {Stringari, A and Tlais, AZA and Tonini, S and Pinto, D and Mondadori, G and Filannino, P and Di Cagno, R and Gobbetti, M}, title = {Revitalising Brewers' Spent Grains and Enriching With Biogenic Compounds Through the Fermentation of Fructophilic Lactic Acid Bacteria and Yeasts.}, journal = {Microbial biotechnology}, volume = {18}, number = {6}, pages = {e70171}, doi = {10.1111/1751-7915.70171}, pmid = {40491241}, issn = {1751-7915}, support = {//Open Access Publishing Fund of the Free University of Bozen-Bolzano/ ; }, mesh = {Fermentation ; *Lactobacillales/metabolism ; *Edible Grain/metabolism/microbiology ; *Saccharomycetales/metabolism ; Filaggrin Proteins ; Antioxidants/metabolism ; Lactic Acid/metabolism ; }, abstract = {The large output of spent grains from the brewing industry presents environmental concerns but also offers promising nutritional and functional potential for valorization by researchers and industrial stakeholders. In this perspective, we investigated how non-conventional starters like Fructobacillus fructosus PL22 and Wickerhamomyces anomalus GY1 can drive the fermentation of brewer's spent grain (BSG), a solid by-product of the brewing industry, to enrich its portfolio of bioactive compounds. While sugar reduction was comparable between started- and unstarted-BSG, the effect of the fermentation became evident through the release of key microbial metabolites (lactic and acetic acids and ethanol). Both starters generated the highest number of unique peptides, with only one previously identified as antioxidant peptide found in BSG fermented with F. fructosus. During fermentation, most amino acids and phenolic compounds decreased, while BSG fermented with W. anomalus distinctly enhanced the release of Ala, Cys and GABA, and health-promoting phenolic compounds, such as gallic acid, gallocatechin, quercetin, naringenin, kaempferol, and isorhamnetin. These metabolic changes were associated with the enhanced antifungal and antioxidant properties, which in turn positively reflected on skin protection as shown by the increased proliferation of human keratinocytes, over-expression of the filaggrin (FLG) gene, and wound healing. The power of fermentation to revitalise BSG, giving it a second life chance through the improvement of its nutritional value and further multifunctionality, was demonstrated.}, }
@article {pmid40488826, year = {2025}, author = {Lee, CJ and Carpenter, PA}, title = {Modern-Era Challenges in the Clinical Management of Graft-Versus-Host Disease.}, journal = {Advances in experimental medicine and biology}, volume = {1475}, number = {}, pages = {103-128}, pmid = {40488826}, issn = {0065-2598}, mesh = {*Graft vs Host Disease/therapy/diagnosis/immunology/etiology ; Humans ; *Hematopoietic Stem Cell Transplantation/adverse effects ; Animals ; Disease Management ; }, abstract = {For several decades, graft-versus-host disease (GVHD) has been a long-standing barrier to successful allogenic hematopoietic cell transplantation and a significant cause of post-transplant morbidity and mortality. Initially described as secondary disease or wasting syndrome in transplanted mice, the pathobiology of GVHD is increasingly understood as a dynamic interplay between innate and adaptive immunity in response to initial tissue damage, leading to inflammation and end-organ damage. In parallel, more uniform symptom capture, diagnosis, and response criteria have facilitated rigorous clinical trial design and conduct; together, these advancements have facilitated the development of novel GVHD prevention and treatment strategies. While these advancements have improved the GVHD treatment paradigm, new questions arise within this complex patient population. This chapter discusses several of the most pertinent current clinical practice challenges in GVHD, including its earlier diagnosis, risk stratification, initial and more advanced stage management, as well as a renewed focus on supportive care, given our increased understanding of key roles played by the human microbiome.}, }
@article {pmid40488467, year = {2025}, author = {Liu, Y and Qiu, Q and Chen, Y and Deng, Y and Huang, W and Sun, C and Shang, X and Chen, X and Wang, C and Han, L and Chen, S and Yuan, J and Xu, F and Yang, Z and Fang, X and Huang, L}, title = {Integrated multi-omics analysis reveals the functional signature of microbes and metabolomics in pre-diabetes individuals.}, journal = {Microbiology spectrum}, volume = {}, number = {}, pages = {e0145924}, doi = {10.1128/spectrum.01459-24}, pmid = {40488467}, issn = {2165-0497}, abstract = {Pre-diabetes (PD) represents a critical stage in the progression toward type 2 diabetes, with significant alterations observed in the human microbial community among pre-diabetic individuals in observational studies. However, understanding the interaction between human microbiota and the host during pre-diabetes remains limited. Therefore, this study aims to understand the alterations in the human microbial community during pre-diabetes, a critical stage toward type 2 diabetes. Using an integrated analysis of human microbiota and metabolomics data, we seek to identify the functional signature associated with PD and gain insights into potential mechanisms driving its progression to type 2 diabetes. These findings could inform the development of early intervention strategies for those at high risk. Samples were collected from pre-diabetes, diabetes, and healthy control groups. Through metagenome and 16S rRNA sequencing, we analyzed the gut microbial and tongue coating compositions, respectively. Untargeted metabolomics techniques were also applied for comprehensive plasma data. Using integrated multi-omics analysis, we aim to understand the metabolic potentials of the human microbiome, its molecular links with host targets, and their effects on pre-diabetes, thereby deepening our understanding of microbiome-host interactions in this context. The pre-diabetes group exhibited distinct clinical characteristics, particularly in blood glucose levels and a higher average level of γ-glutamyl transferase. We identified 509 intestinal bacterial species, with Megamonas funiformis and Parabacteroides merdae showing higher abundance in the PD group. In tongue coating samples, we found 1,122 bacterial genera, with the PD group showing altered levels of Corynebacterium and Johnsonella. Furthermore, we detected 795 metabolites, primarily involved in carbohydrate and lipid metabolism. Importantly, our integrated multi-omics analysis suggested Flavonifractor plautii's role in modulating blood glucose through influencing carbohydrate metabolism. Our integrated multi-omics analysis revealed significant alterations in several regulatory pathways associated with pre-diabetes, particularly emphasizing the impact of gut bacterium Flavonifractor plautii on blood glucose levels through its influence on carbohydrate metabolism. These intricate relationships among gut microbiota, metabolites, and blood glucose levels underscore the significance of personalized treatment approaches and preventive strategies for pre-diabetes. The insights gained from this research hold considerable promise for advancing our understanding and management of pre-diabetes.IMPORTANCEThis study investigates alterations in the human microbial community during PD, a critical stage leading to type 2 diabetes. Through integrated analysis of metagenomic and metabolomics data from pre-diabetes, diabetes, and healthy control groups, we identified distinct clinical characteristics in the PD group, including elevated blood glucose levels and γ-glutamyl transferase. A total of 509 intestinal bacterial species were identified, with Flavonifractor plautii playing a key role in modulating blood glucose levels via its influence on carbohydrate metabolism. Our findings underscore the complex interactions among gut microbiota, metabolites, and blood glucose levels, highlighting the potential for personalized treatment approaches and early intervention strategies for individuals at high risk of developing type 2 diabetes.}, }
@article {pmid40482318, year = {2025}, author = {Häggqvist, IM and Jernman, J and Snellman, E and Kärhä, P and Pasternack, R and Partonen, T and Karisola, P}, title = {Infrared-A (IR-A) modulates the p53 pathway and diurnal clock in human skin and subcutaneous adipose tissue in vivo.}, journal = {Journal of photochemistry and photobiology. B, Biology}, volume = {269}, number = {}, pages = {113199}, doi = {10.1016/j.jphotobiol.2025.113199}, pmid = {40482318}, issn = {1873-2682}, abstract = {Infrared-A (IR-A) radiation is thought to protect the skin from damage due to ultraviolet radiation and alter its carcinogenic potential, possibly by preventing keratinocyte apoptosis via p53 pathway modulation. Solar radiation, including IR-A, is a major factor in contributing to the entrainment of circadian rhythms. We examined the impacts of IR-A on the intrinsic clock and transcriptomics in individuals with different diurnal preference to understand the mechanisms by which IR-A acts in the human skin and subcutaneous adipose tissue. IR-A caused multiple gene expressional changes, mainly as immediate stress responses in 15 min, that were reversed within 24 h. IR-A irradiation increased the skin surface temperature (mean peak temperature 42.9 °C). In skin, the zinc finger proteins ZNF490 and ZNHIT2 correlated negatively with the maximum skin surface temperature. In adipose tissue, CDKN1A, which codes p21 protein, had a negative correlation with the skin surface temperature change. In the skin immunohistochemical staining, the circadian regulators CRY1 and CRY2 increased significantly 24 h after the irradiation, CRY1 already in 15 min. According to the diurnal preferences, morning-type individuals develop mostly innate immune responses, whereas evening-type of individuals had more pronounced responses through p53 pathway modulation, apoptosis, and autophagy.}, }
@article {pmid40479572, year = {2025}, author = {Lee, PJ and Lo, YC and Chen, YY and Hu, CJ and Lin, YK and Trang Pham, QT and Sim, NK and Then, CK and Shen, SC}, title = {Short-Chain Fatty Acids Improve Hippocampal Atrophy, Ventricular Dilatation and Cognitive Function Decline in Aged Mice.}, journal = {Aging and disease}, volume = {}, number = {}, pages = {}, doi = {10.14336/AD.2025.0426}, pmid = {40479572}, issn = {2152-5250}, abstract = {Many countries are becoming aged or super-aged societies. This demographic shift causes substantial social, economic, and personal costs directly and indirectly attributable to cognitive decline. Recent studies have shown that dietary fiber can slow down memory decline, with short-chain fatty acids being the primary metabolites produced by gut microbiota from the fermentation of dietary fiber. Despite this, there are limited studies investigating the effect of SCFAs on age-related cognitive function and morphological changes of the brain. In this study, we used B6C3F1 male mice at the age of 3 months and treated them with water, low dose, and high dose SCFAs for 9 months. We assessed their short- and long-term cognitive functions using the Novel Object Recognition test, Morris Water Maze, and Rotarod test. Their brain structure was assessed by 7 Tetra Magnetic Resonance Imaging (7TMRI) and gut microbiota analyzed by 16S rRNA sequencing. Our results show that both short-term and long-term SCFA treatment significantly improve cognitive deficits in the Novel Objective Recognition test and Morris Water Maze tests. Additionally, the 7T MRI results show that SCFAs mitigated hippocampal atrophy compared to the control group. These improvements were accompanied by alteration of gut microbiota composition. We also found that, after treatment, the beneficial gut microbiota Alloprevotella was positively correlated with hippocampal volume. Therefore, we propose that SCFAs may be a promising therapeutic strategy to counteract age-related cognitive decline.}, }
@article {pmid40476583, year = {2025}, author = {Jang, JY and Seo, JH and Choi, JJ and Ryu, HJ and Yun, H and Ha, DM and Yang, J}, title = {Insight into microbial extracellular vesicles as key communication materials and their clinical implications for lung cancer (Review).}, journal = {International journal of molecular medicine}, volume = {56}, number = {2}, pages = {}, doi = {10.3892/ijmm.2025.5560}, pmid = {40476583}, issn = {1791-244X}, mesh = {Humans ; *Extracellular Vesicles/metabolism ; *Lung Neoplasms/microbiology/metabolism/pathology/etiology ; Microbiota ; Animals ; Cell Communication ; *Bacteria/metabolism ; Dysbiosis ; Lung/microbiology ; }, abstract = {The complexity of lung cancer, driven by multifactorial causes such as genetic, environmental and lifestyle factors, underscores the necessity for tailored treatment strategies informed by recent advancements. Studies highlight a significant association between the lung microbiome and lung cancer, with dysbiosis potentially contributing to disease development via inflammation, immune response alterations and bacterial metabolite production. Furthermore, exposure to airborne bacteria may influence lung health by introducing pathogenic species or altering the human microbiome, thereby implicating certain dominant airborne bacteria in lung diseases, including the exacerbation of lung cancer. Extracellular vesicles (EVs) facilitate cell‑to‑cell communication, penetrating mucosal barriers to impact various organs, notably the lung. Epidemiological evidence suggests a strong relationship between the presence of microbial EVs (MEVs) in the air and chronic pulmonary diseases, with indications of a potential risk for lung cancer. MEVs play a significant role in pulmonary disease development by inducing airway inflammation and affecting lung function. The microbiome and MEVs offer considerable potential as novel tools in precision medicine for lung cancer. Biological data analysis and artificial intelligence technology advancements are pivotal for fully realizing their diagnostic and therapeutic capabilities. These developments can potentially shape the future landscape of lung cancer diagnostics, therapeutics and prevention strategies.}, }
@article {pmid40476157, year = {2025}, author = {Rashid, M and Pereira, HS and Alissa, A and Keraidi, S and Wipf, N and Sowa, AM and McDonnell, JM and Darwish, S and Butler, JS}, title = {Microbiome dysbiosis in spinal pathology: Mechanisms, evidence, and research limitations.}, journal = {Brain &amp; spine}, volume = {5}, number = {}, pages = {104272}, pmid = {40476157}, issn = {2772-5294}, abstract = {INTRODUCTION: The microbiome's relevance has become increasingly discussed amid the rising prevalence of chronic illnesses. Microbiome research to date focuses predominantly on its relationship with the GI tract while largely ignoring any impact on the rest of the body. This narrative review aims to lay a foundation of knowledge to fill this gap in the literature and discuss other microbiomes within the human body and their relation to spinal health.<br><br>RESEARCH QUESTION: What is the relationship between the human microbiome and spinal pathologies?<br><br>MATERIALS AND METHODS: A narrative review of all available literature (written or translated to English) was performed using PubMed, MEDLINE, and Google Scholar using relevant search terms including: "microbiome", "spine", "spinal pathology", "ankylosing spondylitis", and "seronegative arthropathies".<br><br>RESULTS: This review found that with dysbiosis, specific bacterial such as Bacteroidaceae and Rikenellaceae proliferate, altering the cytokine microenvironment and subsequently increasing gut wall permeability. This immune overactivation and improper cell function results in an increased susceptibility to autoimmunity; specifically ankylosing spondylitis and seronegative arthropathies. This review also highlights the significant gaps in the available literature.<br><br>DISCUSSION AND CONCLUSION: This review aims to equip clinicians with an understanding of how the collection of microbiomes in the human body have specific implications for spinal health. By building on the current literature and integrating this knowledge into practice, more patient-specific practices in the treatment of spinal pathologies can be implemented, ultimately improving and optimizing patient care in a field in which the microbiome is not currently at the forefront of pathology.}, }
@article {pmid40474070, year = {2025}, author = {Boodaghidizaji, M and Jungles, T and Chen, T and Zhang, B and Yao, T and Landay, A and Keshavarzian, A and Hamaker, B and Ardekani, A}, title = {Machine learning based gut microbiota pattern and response to fiber as a diagnostic tool for chronic inflammatory diseases.}, journal = {BMC microbiology}, volume = {25}, number = {1}, pages = {353}, pmid = {40474070}, issn = {1471-2180}, abstract = {Gut microbiota has been implicated in the pathogenesis of multiple gastrointestinal (GI) and systemic metabolic and inflammatory disorders where disrupted gut microbiota composition and function (dysbiosis) has been found in multiple studies. Thus, human microbiome data holds significant potential as a source of information for diagnosing and characterizing diseases-such as phenotypes, disease course, and therapeutic response-associated with dysbiotic microbiota communities. However, multiple attempts to leverage gut microbiota taxonomic data for diagnostic and disease characterization have failed due to significant inter-individual variability of microbiota community and overlap of disrupted microbiota communities among multiple diseases. One potential approach is to look at the microbiota community pattern and response to microbiota modifiers like dietary fiber in different disease states. This approach has become feasible with the advent of machine learning, which can uncover hidden patterns in human microbiome data and enable disease prediction. Accordingly, the aim of our study was to test the hypothesis that machine learning algorithms can distinguish stool microbiota patterns-and their responses to fiber-across diseases with previously reported overlapping dysbiotic microbiota profiles. Here, we applied machine learning algorithms to distinguish between Parkinson's disease, Crohn's disease (CD), ulcerative colitis (UC), human immune deficiency virus (HIV), and healthy control (HC) subjects in the presence and absence of fiber treatments. We demonstrated that machine learning algorithms can classify diseases with accuracy as high as 95%. Furthermore, applying machine learning to microbiome data to distinguish UC from CD yielded a prediction accuracy of up to 90%.}, }
@article {pmid40473134, year = {2025}, author = {Sadeghi, S and Faramarzi, MA and Siroosi, M}, title = {Design of Novel Human Microbiome-Derived Peptides for Inhibition of OXA-48 Carbapenemase: An In-Silico and In-Vitro Approach.}, journal = {Microbial pathogenesis}, volume = {}, number = {}, pages = {107779}, doi = {10.1016/j.micpath.2025.107779}, pmid = {40473134}, issn = {1096-1208}, abstract = {Drug-resistant bacteria have become a global healthcare challenge, especially due to their acquisition of resistance to last-resort antibiotics. OXA-48 carbapenemase is one of the notorious enzymes that inactivates carbapenems through hydrolysis. The emergence of OXA-48 and OXA-48-like carbapenemases is a significant concern as they are responsible for many outbreaks of hospital-acquired infections in various countries, with limited treatment options available. Thus, targeting this enzyme and inhibiting its activity can be an attractive therapeutic strategy. In this study, a rational computer-aided approach was applied to design effective inhibitory peptides against OXA-48 carbapenemase. The primary library was constructed based on peptides derived from the Human Antimicrobial Peptide (HAMP) database. The binding of peptides to the enzyme was investigated through molecular docking studies using ClusPro. After each screening step, numerous targeted amino acid substitutions were performed to enhance the affinity and physicochemical properties of the selected peptides. The final selected peptides, in complex with the enzyme, were subjected to 200 ns Molecular Dynamics (MD) simulations using the GROMACS package, and MM/PBSA analysis was conducted to evaluate the binding free energy of the enzyme-peptide complexes. Finally, the inhibitory effects of the designed peptides were also computationally assessed on OXA-48-like carbapenemases. Homology modeling was used to generate 3D structures of the enzymes whose structures were not solved experimentally. Results indicated that the two final selected peptides effectively interacted with the important residues of OXA-48 carbapenemase and spatially blocked its active site. These peptides also demonstrated high binding affinity to the most common OXA-48-like carbapenemases in silico. In vitro studies on the efficacy of one of the designed peptides, M104, demonstrated that this peptide enhanced the activity of meropenem against a meropenem-resistant, clinical Klebsiella pneumoniae strain harboring the gene blaOXA48 by reducing its minimum inhibitory concentration (MIC) by 4-fold. In an era where effective inhibitors against OXA-48 carbapenemase are limited, present study addressed this urgent need by rationally designed novel peptides.}, }
@article {pmid40470258, year = {2025}, author = {Demirci, M and Gadhave, K}, title = {Editorial: Human microbiome and COVID-19.}, journal = {Frontiers in cellular and infection microbiology}, volume = {15}, number = {}, pages = {1613825}, pmid = {40470258}, issn = {2235-2988}, }
@article {pmid40468659, year = {2025}, author = {Hossain, MS and Seo, H and Lee, KA and Ul-Haq, A and Kim, S and Jo, S and Rahim, MA and Tajdozian, H and Ghorbanian, F and Yoon, Y and Barman, I and Shuvo, MSH and Kim, HS and Song, HY}, title = {Microbiome therapeutic PMC72 through reverse translational research in gout.}, journal = {Journal of microbiology (Seoul, Korea)}, volume = {63}, number = {5}, pages = {e2501002}, doi = {10.71150/jm.2501002}, pmid = {40468659}, issn = {1976-3794}, support = {RS-202300219563//National Research Foundation of Korea/ ; //Ministry of Science and ICT/ ; 2020R1I1A-3072680//Ministry of Education/ ; //Soonchunhyang University Research Fund/ ; }, mesh = {Animals ; *Gout/therapy/microbiology/chemically induced ; Humans ; Mice ; *Gastrointestinal Microbiome/drug effects ; Hyperuricemia/chemically induced/therapy ; Uric Acid/blood/metabolism ; Disease Models, Animal ; Translational Research, Biomedical ; Dysbiosis ; Male ; Feces/microbiology ; Febuxostat/therapeutic use ; Oxonic Acid ; Oxidative Stress ; }, abstract = {Gout is an inflammatory arthritis resulting from the deposition of monosodium urate crystals. Urate-lowering therapies for gout have limitations, including side effects and limited efficacy, highlighting the need for novel therapeutic approaches to improve patient outcomes. In this context, our research team conducted a microbiome analysis of fecal samples from healthy individuals and gout patients, identifying Bifidobacterium as a key biomarker. Subsequently, we isolated and identified this strain, B. longum PMC72, and demonstrated its efficacy in a gout mouse model. In potassium oxonate (PO)-induced hyperuricemia mice, PMC72 significantly alleviated nausea, gait disturbances, ankle inflammation, and improved renal health. These effects were associated with marked reductions in oxidative stress markers, including serum uric acid, blood urea nitrogen, hepatic xanthine oxidase, and malondialdehyde (MDA) levels in serum, liver, and joint samples, as well as the downregulation of inflammation and uric acid transport-related gene expression in kidney samples. These benefits were comparable to those treated with Febuxostat, a standard urate-lowering therapy for gout. Furthermore, gut microbiome analysis revealed that PMC72 restored dysbiosis induced by hyperuricemia, contrasting with the reduced microbial diversity observed with febuxostat alone, and showed a complete recovery to eubiosis when combined with Febuxostat. These findings position PMC72 as a promising microbial therapeutic candidate for gout management, demonstrating significant development potential and serving as a benchmark for reverse translational microbiome-based therapeutic research.}, }
@article {pmid40467859, year = {2025}, author = {Ferretti, P and Johnson, K and Priya, S and Blekhman, R}, title = {Genomics of host-microbiome interactions in humans.}, journal = {Nature reviews. Genetics}, volume = {}, number = {}, pages = {}, pmid = {40467859}, issn = {1471-0064}, abstract = {The human microbiome is a complex ecosystem of microorganisms that inhabit the human body and have a crucial role in human health. Microbiome composition is shaped by its interaction with many factors, including human genetics. Advances in genomic technologies are improving the ability to quantify the effect of human genetics on the microbiome through improved heritability studies and microbiome genome-wide association studies (GWAS). Complementary studies using transcriptomic analyses are providing a more comprehensive view of the bidirectional relationship between host gene expression and the microbiome. The resulting insights into the genetic mechanisms driving host-microbiome interactions will ultimately contribute to the development of personalized medicine and targeted therapies.}, }
@article {pmid40467839, year = {2025}, author = {Chen, YA and Kawashima, H and Park, J and Mohsen, A and Hosomi, K and Nakagata, T and Murakami, H and Nanri, H and Miyachi, M and Kunisawa, J and Mizuguchi, K}, title = {NIBN Japan Microbiome Database, a database for exploring the correlations between human microbiome and health.}, journal = {Scientific reports}, volume = {15}, number = {1}, pages = {19640}, pmid = {40467839}, issn = {2045-2322}, support = {22AC5002//Ministry of Health, Labour and Welfare/ ; 22AC5002//Ministry of Health, Labour and Welfare/ ; 20AC5004//Ministry of Health, Labour and Welfare/ ; 20AC5004//Ministry of Health, Labour and Welfare/ ; }, abstract = {Recent research has highlighted the substantial impact of gut microbiome on various aspects of human health, such as obesity, inflammation, infectious diseases, and cancer. As a result, gut microbiota composition is increasingly recognized as a potential health indicator and biomarker for disease. Numerous factors, including lifestyle, diet, and physical fitness, are known to shape the composition of the human microbiome. However, a significant challenge in elucidating the relationships between these factors and the gut microbiome lies in needing a comprehensive database that integrates diverse human microbiome profiles with extensive sample metadata. To address this issue, we developed an extensive human microbiome database for healthy individuals. This initiative led to the establishment of the NIBN Japan Microbiome Database (NIBN JMD), one of the largest resources of its kind, encompassing up to 1,000 metadata points and more than 2,000 microbiome samples, including data from longitudinal studies. In this article, we describe the creation and features of NIBN JMD, detailing the data collection, processing, and database implementation. NIBN JMD is publicly accessible at https://jmd.nibn.go.jp/ .}, }
@article {pmid40456421, year = {2025}, author = {Talukdar, D and Raju, YJ and Jana, P and Sharma, K and Babele, P and Kothidar, A and Ahrodia, T and Narendrakumar, L and Shyam, KR and Singh, U and Tanwar, S and Harle, S and Chaudhuri, S and Raghavan, S and Wadhwa, N and Mukherjee, S and Bhatnagar, S and Das, B and , }, title = {Genomic insights into the potency and functional roles of Lactobacillus species in term and preterm births.}, journal = {Genomics}, volume = {}, number = {}, pages = {111063}, doi = {10.1016/j.ygeno.2025.111063}, pmid = {40456421}, issn = {1089-8646}, abstract = {The vaginal microbiome, typically dominated by Lactobacillus species, plays a key role in reducing the risk of preterm birth (PTB) by protecting against infections. In this study, we sequenced 133 Lactobacillus genomes isolated from the reproductive tracts of pregnant Indian women. Genomic analysis identified genes linked to pathogen resistance and anti-inflammatory functions. Further proteome analysis of cell-free supernatant revealed antimicrobial properties, including lysin and bacteriocin, while antibacterial tests confirmed their ability to inhibit reproductive tract pathogens. These findings suggest that Lactobacillus strains protect against harmful microbes, potentially reducing infection risks and PTB. This Lactobacillus consortium holds promise for developing biotherapeutics aimed at improving maternal health.}, }
@article {pmid40456384, year = {2025}, author = {Nayyar, J and Bedu-Ferrari, C and Patangia, D and Hurley, E and Feeley, L and Ross, RP and Stanton, C and Brady, P}, title = {Gut and oral microbial profile associations to oral cancer.}, journal = {Journal of dentistry}, volume = {}, number = {}, pages = {105848}, doi = {10.1016/j.jdent.2025.105848}, pmid = {40456384}, issn = {1879-176X}, abstract = {The human microbiome is widely known to be associated with health and disease. The oral microbiome has been linked with oral diseases and infections, though not many studies have explored the relation between oral and gut microbiome with oral cancer based on lesion histology METHODS: This study uniquely explores the oral and gut microbiota in 30 participants (n=30) divided into three groups based on histology; Benign (B) (n=15), Potentially Malignant (PM) (n=8), and Malignant (M) (n=7) oral lesions. Using shotgun metagenomic sequencing, we analysed microbiota profiles to determine their potential as biomarkers for oral malignancy RESULTS: Distinct gut microbial profiles were observed between Benign and Malignant groups and the association of specific microbes in oral saliva, such as Haemophilus parainfluenzae, Veillonella parvula, Fusobacterium nucleatum and Rothia mucilaginosa were strongly associated with malignancy CONCLUSION: The data from this exploratory study suggest that oral and gut microbiomes could act as possible biomarkers and aid in early detection and assessment of oral cancer risk. With regard to potentially malignant lesions, future research could study individual Oral Potentially Malignant Disorders (OPMDs) as distinct entities due to the wide variation in clinical and histological presentation. Further research is required to develop definitive biomarkers in both potentially malignant and malignant oral lesions CLINICAL SIGNIFICANCE: While smoking and alcohol are known risk factors for oral cancer, a biomarker such as the saliva/stool microbiome profile could help identify a risk indicator or a potential risk factor. Additionally such a biomarker could help identify patients with OPMDs that are likely to undergo malignant transformation.}, }
@article {pmid40455399, year = {2025}, author = {Qayyum, H and Raziq, MF and Manzoor, H and Zaidi, SSA and Ali, A and Kayani, MUR}, title = {Efficient De Novo Assembly and Recovery of Microbial Genomes from Complex Metagenomes Using a Reduced Set of k-mers.}, journal = {Interdisciplinary sciences, computational life sciences}, volume = {}, number = {}, pages = {}, pmid = {40455399}, issn = {1867-1462}, abstract = {De novo assembly and genome binning are fundamental steps for genome-resolved metagenomics analyses. However, the availability of limited computational resources and extensive processing time limit the broader application of these analyses. To address these challenges, the optimization of the parameters employed in these processes can improve the effective utilization of available metagenomics tools. Therefore, this study tested three sets of k-mers (default, reduced, and extended) for their efficiency in metagenome assembly and suitability in recovering metagenome-assembled genomes. The results demonstrate that the reduced set of k-mers outperforms the other two sets in computational efficiency and the quality of results. The assemblies from the default set are comparable with those from the reduced set; however, less complete and highly contaminated metagenome-assembled genomes are obtained at the expense of higher processing time. The extended set of k-mers yields less contiguous but computationally expensive assemblies. This set takes approximately 3-times more processing time than the reduced k-mers and recovers the lowest proportions of high and medium-quality metagenome-assembled genomes. Contrarily, the reduced set produces better assemblies, substantially improving the number and quality of the recovered metagenome-assembled genomes in significantly reduced processing time. Validation of the reduced k-mer set on previously published metagenome datasets further demonstrates its effectiveness not only for human metagenomes but also for the metagenomes of environmental origin. These findings underscore that the reduced k-mer set is optimal for efficient metagenome analyses of varying complexities and origins. This optimization of the k-mer set used in metagenome assemblers significantly reduces computational time while improving the quality of the assemblies and recovered metagenome-assembled genomes. This efficient solution will facilitate the widespread application of genome-resolved analyses, even in resource-limited settings, and help the recovery of better-quality metagenome-assembled genomes for downstream analyses.}, }
@article {pmid40454482, year = {2025}, author = {Koletic, C and Mrad, A and Martin, A and Devkota, S}, title = {Diet's impact on gut microbial assemblage in health and disease.}, journal = {The Journal of clinical investigation}, volume = {135}, number = {11}, pages = {}, doi = {10.1172/JCI184319}, pmid = {40454482}, issn = {1558-8238}, mesh = {Humans ; *Gastrointestinal Microbiome ; *Diet ; Animals ; Chronic Disease ; }, abstract = {The gut microbiome has been linked to everything from human behavior to athletic performance to disease pathogenesis. And yet, few universal truths have emerged regarding how the microbiome exerts its effects or responds to the host environment except for one: gut microbiota are exquisitely sensitive to human diets. What we eat from birth onward shapes our gut microbiome composition and function, and this is likely an evolutionarily conserved interaction that benefits the microbe and often the host. However, modern diets and lifestyles have created discordance between our slowly evolving human genome and rapidly adaptable microbiome, and have been implicated in the rise of chronic diseases over the past 75 years. Diet and microbiome interactions have been reviewed extensively, so here we focus on areas of microbiome research that have most illuminated natural and disruptive dietary forces over time in humans, and where we may have opportunities to restore the natural balance of host with microbes in our modern world.}, }
@article {pmid40448869, year = {2025}, author = {Dash, HR and Al-Snan, NR}, title = {DNA forensics at forty: the way forward.}, journal = {International journal of legal medicine}, volume = {}, number = {}, pages = {}, pmid = {40448869}, issn = {1437-1596}, abstract = {Forensic DNA analysis has transformed criminal investigations since its inception in 1985. Over four decades, this field has evolved through various phases-from the early stages of exploration to today's highly sophisticated methodologies. Key advancements such as the development of rapid DNA analysis techniques, microchip-based systems, and next-generation sequencing have improved the speed, reliability, and utility of DNA forensics. However, despite these technological advances, the field still faces considerable challenges, particularly with increasing case backlogs, limited population-specific databases, and the difficulties associated with analyzing degraded or challenging samples like bones and touch DNA. Emerging technologies such as single-cell genomic analysis, lineage markers, proteomics, and human microbiome analysis offer promising solutions to these challenges. Furthermore, the integration of artificial intelligence (AI) and machine learning (ML) in forensic workflows is enhancing the ability to analyze complex DNA samples efficiently, paving the way for faster and more accurate results. As forensic DNA analysis enters its next phase, the focus will be on expanding databases, refining quality control and assurance protocols, and standardizing training for forensic professionals worldwide. The journey of forensic DNA analysis over the past 40 years demonstrates a field in continuous development. Although significant progress has been made, there remain opportunities for further innovation, particularly in overcoming the current limitations and addressing ethical and legal concerns. By doing so, forensic DNA analysis will continue to play a pivotal role in the future of criminal justice.}, }
@article {pmid40448308, year = {2025}, author = {Gu, BH and Jung, HY and Rim, CY and Kim, TY and Lee, SJ and Choi, DY and Park, HK and Kim, M}, title = {Comparative Colonisation Ability of Human Faecal Microbiome Transplantation Strategies in Murine Models.}, journal = {Microbial biotechnology}, volume = {18}, number = {6}, pages = {e70173}, doi = {10.1111/1751-7915.70173}, pmid = {40448308}, issn = {1751-7915}, support = {2024-ER2113-00//the Korea National Institute of Health (KNIH) research project/ ; 20019505//the Ministry of Trade, Industry &amp; Energy (MOTIE, Korea)/ ; }, mesh = {Animals ; *Fecal Microbiota Transplantation/methods ; Humans ; Mice ; *Gastrointestinal Microbiome ; *Feces/microbiology ; Disease Models, Animal ; *Bacteria/classification/growth &amp; development/isolation &amp; purification/genetics ; Dysbiosis/therapy/microbiology ; Male ; Models, Animal ; }, abstract = {The gut microbiome plays a crucial role in maintaining intestinal homeostasis and influencing immune-mediated diseases. Human faecal microbiota transplantation (FMT) is often employed in murine models to investigate the role of human microbes in disease regulation, but methods for effective colonisation require refinement. This study aimed to assess the colonisation efficiency of human microbiota in a murine model using FMT with human faeces, focusing particularly on the impact of gut microbiota depletion via polyethylene glycol (PEG) and comparing oral-gastric gavage with enema administration routes. Our findings revealed that PEG-induced depletion enhanced human microbiome colonisation in mice. Oral-gastric gavage prolonged colonisation, while enema administration facilitated quicker resolution of dysbiosis, both inducing selective human microbial colonisation in a time-dependent manner. Notably, genera such as Bacteroides, Blautia, Medicaternibacter and Bifidobacteria were successfully colonised, whereas Roseburia, Anaerostipes, Anaerobutyricum and Faecalibacterium failed to establish in the murine gut post-FMT. These findings highlight the challenges of replicating human gut microbiota in murine models and underscore the importance of selecting appropriate FMT methods based on desired outcomes. This study provides valuable insights into the colonisation dynamics of human microbiota in mice, contributing to the development of more effective FMT strategies for disease treatment.}, }
@article {pmid40441709, year = {2025}, author = {Dang, T and Fuji, Y and Kumaishi, K and Usui, E and Kobori, S and Sato, T and Narukawa, M and Toda, Y and Sakurai, K and Yamasaki, Y and Tsujimoto, H and Hirai, MY and Ichihashi, Y and Iwata, H}, title = {I-SVVS: integrative stochastic variational variable selection to explore joint patterns of multi-omics microbiome data.}, journal = {Briefings in bioinformatics}, volume = {26}, number = {3}, pages = {}, doi = {10.1093/bib/bbaf132}, pmid = {40441709}, issn = {1477-4054}, support = {JP21J21850//JSPS KAKENHI/ ; JPMJCR1602//JST-CREST Program/ ; JPMJMI120C7//JST-Mirai Program/ ; JPMJAN23D1//JST ALCA-Next Program/ ; }, mesh = {*Microbiota ; Mice ; Animals ; Humans ; Stochastic Processes ; Bayes Theorem ; Glycine max/microbiology ; *Metabolomics/methods ; Algorithms ; *Computational Biology/methods ; Metabolome ; Cluster Analysis ; Multiomics ; }, abstract = {High-dimensional multi-omics microbiome data play an important role in elucidating microbial community interactions with their hosts and environment in critical diseases and ecological changes. Although Bayesian clustering methods have recently been used for the integrated analysis of multi-omics data, no method designed to analyze multi-omics microbiome data has been proposed. In this study, we propose a novel framework called integrative stochastic variational variable selection (I-SVVS), which is an extension of stochastic variational variable selection for high-dimensional microbiome data. The I-SVVS approach addresses a specific Bayesian mixture model for each type of omics data, such as an infinite Dirichlet multinomial mixture model for microbiome data and an infinite Gaussian mixture model for metabolomic data. This approach is expected to reduce the computational time of the clustering process and improve the accuracy of the clustering results. Additionally, I-SVVS identifies a critical set of representative variables in multi-omics microbiome data. Three datasets from soybean, mice, and humans (each set integrated microbiome and metabolome) were used to demonstrate the potential of I-SVVS. The results indicate that I-SVVS achieved improved accuracy and faster computation compared to existing methods across all test datasets. It effectively identified key microbiome species and metabolites characterizing each cluster. For instance, the computational analysis of the soybean dataset, including 377 samples with 16 943 microbiome species and 265 metabolome features, was completed in 2.18 hours using I-SVVS, compared to 2.35 days with Clusternomics and 1.12 days with iClusterPlus. The software for this analysis, written in Python, is freely available at https://github.com/tungtokyo1108/I-SVVS.}, }
@article {pmid40436194, year = {2025}, author = {Chang, VC and Purandare, V and Li, S and Andreotti, G and Hua, X and Wan, Y and Dagnall, CL and Jones, K and Hicks, BD and Hutchinson, A and Yano, Y and Dalton, KR and Lee, M and Parks, CG and London, SJ and Sandler, DP and Gail, MH and Shi, J and Hofmann, JN and Sinha, R and Abnet, CC and Vogtmann, E and Beane Freeman, LE}, title = {Animal farming and the oral microbiome in the Agricultural Health Study.}, journal = {Environmental research}, volume = {}, number = {}, pages = {121964}, doi = {10.1016/j.envres.2025.121964}, pmid = {40436194}, issn = {1096-0953}, abstract = {BACKGROUND: Raising farm animals imparts various exposures that may shape the human microbiome. The oral microbiome has been increasingly implicated in disease development. Animal farming has also been associated with certain chronic diseases such as cancer; however, underlying biological mechanisms are unclear. We investigated associations between raising farm animals and the oral microbiome in the Agricultural Health Study.<br><br>METHODS: This analysis included 1,245 participants (865 farmers and 380 spouses) who provided oral wash specimens and information on types and numbers of specific animals raised on their farms within 2 years before sample collection. The oral microbiome was measured by sequencing the V4 region of the 16S ribosomal RNA gene. We evaluated associations of farm animal exposures with alpha and beta diversity metrics (within- and between-sample diversity, respectively), as well as presence and relative abundance of specific bacterial genera. All analyses adjusted for potential confounders (e.g., age, sex, smoking, alcohol consumption).<br><br>RESULTS: Overall, 63% of participants raised farm animals, most commonly cattle (46%) and hogs (20%). Those who raised a large number of hogs (&#x2265;2,000 vs. no hogs) had higher alpha diversity. Conversely, raising sheep/goats and raising larger numbers of poultry were associated with lower alpha diversity. Beta diversity was not significantly different between participants with and without any farm animals. Participants raising any farm animals had higher relative abundance of Porphyromonas and lower relative abundances of Prevotella and Ruminococcaceae UCG-014. Several genera were more likely to be absent with specific animal exposures (e.g., Capnocytophaga for cattle and sheep/goats; Corynebacterium, Dialister, Stomatobaculum, and Solobacterium for sheep/goats and poultry).<br><br>CONCLUSIONS: This was the largest study of farm animal exposures and the human microbiome to date. Findings suggest that raising specific farm animals may influence the oral microbiome, supporting the need to further investigate the potential role of animal farming in disease etiology.}, }
@article {pmid40434093, year = {2025}, author = {Koldaş, SS and Sezerman, OU and Timuçin, E}, title = {Exploring the role of microbiome in cystic fibrosis clinical outcomes through a mediation analysis.}, journal = {mSystems}, volume = {}, number = {}, pages = {e0019625}, doi = {10.1128/msystems.00196-25}, pmid = {40434093}, issn = {2379-5077}, abstract = {UNLABELLED: Human microbiome plays a crucial role in host health and disease by mediating the impact of environmental factors on clinical outcomes. Mediation analysis is a valuable tool for dissecting these complex relationships. However, existing approaches are primarily designed for cross-sectional studies. Modern clinical research increasingly utilizes long follow-up periods, leading to complex data structures, particularly in metagenomic studies. To address this limitation, we introduce a novel mediation framework based on structural equation modeling that leverages linear mixed-effects models using penalized quasi-likelihood estimation with a debiased lasso. We applied this framework to a 16S rRNA sputum microbiome data set collected from patients with cystic fibrosis over 10 years to investigate the mediating role of the microbiome in the relationship between clinical states, disease aggressiveness phenotypes, and lung function. We identified richness as a key mediator of lung function. Specifically, Streptococcus was found to be significantly associated with mediating the decline in lung function on treatment compared to exacerbation, while Gemella was associated with the decline in lung function on recovery. This approach offers a powerful new tool for understanding the complex interplay between microbiome and clinical outcomes in longitudinal studies, facilitating targeted microbiome-based interventions.<br><br>IMPORTANCE: Understanding the mechanisms by which the microbiome influences clinical outcomes is paramount for realizing the full potential of microbiome-based medicine, including diagnostics and therapeutics. Identifying specific microbial mediators not only reveals potential targets for novel therapies and drug repurposing but also offers a more precise approach to patient stratification and personalized interventions. While traditional mediation analyses are ill-equipped to address the complexities of longitudinal metagenomic data, our framework directly addresses this gap, enabling robust investigation of these increasingly common study designs. By applying this framework to a decade-long cystic fibrosis study, we have begun to unravel the intricate relationships between the sputum microbiome and lung function decline across different clinical states, yielding insights that were previously unknown.}, }
@article {pmid40433658, year = {2025}, author = {Śmiga, M and Olczak, T}, title = {HmuY proteins of the Porphyromonas genus show diversity in heme-binding properties.}, journal = {Frontiers in cellular and infection microbiology}, volume = {15}, number = {}, pages = {1560779}, pmid = {40433658}, issn = {2235-2988}, mesh = {*Heme/metabolism ; *Bacterial Proteins/metabolism/genetics/chemistry ; Humans ; *Porphyromonas gingivalis/metabolism/genetics ; Protein Binding ; *Porphyromonas/metabolism/genetics ; Computational Biology ; Phylogeny ; Iron/metabolism ; Protoporphyrins/metabolism ; Binding Sites ; }, abstract = {INTRODUCTION: Bacteria of the Porphyromonas genus, belonging to the Bacteroidota phylum, colonize various host niches in health and disease. As heme auxotrophs, they rely on heme uptake for iron and protoporphyrin IX. A key heme acquisition system in Porphyromonas gingivalis is the Hmu system, where the hemophore-like HmuY[Pg] protein plays a major role. HmuY[Pg] coordinates heme-iron using two histidines, whereas other known HmuY proteins produced by other Bacteroidota members prefer a pair of histidine-methionine or two methionines. Some of them bind heme via the protoporphyrin ring without heme-iron coordination, similar to the P. gingivalis HusA protein.<br><br>METHODS: This study used bioinformatics, spectroscopic, and electrophoretic methods to compare the genomic organization of the Hmu system and the structural and functional properties of HmuY proteins within the Porphyromonas genus.<br><br>RESULTS AND DISCUSSION: We revealed variations in the heme-binding properties of proteins belonging to the HmuY family and susceptibility to modifications in their heme-binding pockets. These findings suggest that HmuY proteins may have undergone evolutionary adaptations to enhance bacterial survival in the human microbiome, contributing to dysbiosis and disease development. These evolutionary changes may explain the superior heme-binding ability of P. gingivalis HmuY[Pg] compared to HmuY homologs produced by other Porphyromonas species.}, }
@article {pmid40430019, year = {2025}, author = {Kozhakhmetov, S and Kossumov, A and Zhakupova, T and Polyakova, T and Imambayeva, N and Syzdykova, B and Rakhmankulova, A and Dalibayeva, G and Kovenskiy, A and Jarmukhanov, Z and Issilbayeva, A and Vinogradova, E and Kushugulova, A}, title = {Characterization of Gut Microbiome Composition in Depression and Completed Suicide.}, journal = {International journal of molecular sciences}, volume = {26}, number = {10}, pages = {}, doi = {10.3390/ijms26104880}, pmid = {40430019}, issn = {1422-0067}, support = {AP19676162//Science Committee of the Ministry of Science and Higher Education of the Republic of Kazakhstan/ ; }, mesh = {Humans ; *Gastrointestinal Microbiome ; Male ; Female ; *Depression/microbiology ; Middle Aged ; Adult ; *Suicide, Completed/psychology ; Feces/microbiology ; Dysbiosis/microbiology ; Energy Metabolism ; }, abstract = {Growing evidence supports a bidirectional relationship between the gut microbiome and mental health. This study investigated the association between gut microbiota, depression, and suicidal behavior by analyzing fecal samples from 35 individuals with varying depression levels and 36 completed suicide cases. Standardized psychometric assessments were used for depression evaluation. Analysis revealed significant taxonomic differences between groups, with increased abundance of Firmicutes, Clostridia, Lachnospiraceae, Blautia, and Dorea in suicide cases, which also positively correlated with depression severity. Metabolic pathway analysis demonstrated a notable dichotomy: suicide cases showed elevated pathways related to infection processes, inflammation, and antibiotic resistance, while the control group exhibited higher energy metabolism and vitamin synthesis pathways. The findings establish specific microbiome profiles associated with both depression symptoms and suicidal behavior, suggesting that gut dysbiosis may influence mental health through altered energy metabolism and inflammatory processes, potentially offering new perspectives for diagnostic and therapeutic approaches.}, }
@article {pmid40423870, year = {2025}, author = {Zhang, M and Zhang, H and Hong, A and Huang, J and Yang, L and Long, Y and Yu, Z}, title = {Dynamic changes of dental plaque and saliva microbiota in OSCC progression.}, journal = {Clinical oral investigations}, volume = {29}, number = {6}, pages = {314}, pmid = {40423870}, issn = {1436-3771}, support = {32170071//This work was funded by the National Natural Science Foundation of China/ ; 82273466//This work was funded by the National Natural Science Foundation of China/ ; 2023ZJ1120//Hunan Provincial Science and Technology Department/ ; 2024JJ2039//Natural Science Foundation of Hunan Province/ ; 2024JJ8117//Natural Science Foundation of Hunan Province/ ; }, mesh = {Humans ; *Saliva/microbiology ; Disease Progression ; *Dental Plaque/microbiology ; *Mouth Neoplasms/microbiology/pathology ; *Carcinoma, Squamous Cell/microbiology/pathology ; Female ; *Microbiota ; Male ; Middle Aged ; Neoplasm Staging ; Metagenomics ; }, abstract = {OBJECTIVES: To elucidate the changes in microbial composition and genomics in saliva and dental plaque during the progression of Oral Squamous Cell Carcinoma (OSCC), and to identify virulence factors and pathways associated with tumor differentiation in OSCC patients.<br><br>MATERIALS AND METHODS: Using metagenomic sequencing, 64 saliva and dental plaque samples from OSCC patients at different stages of differentiation were examined.<br><br>RESULTS: The results showed notable differences in the microbial composition and genomic profiles across ecological regions and differentiation degrees. Notably, the relative abundance of specific microbes, such as Porphyromonas gingivalis, Fusobacterium nucleatum, and Haemophilus parainfluenzae, increased in poorly differentiated OSCC. Microbial alpha diversity in dental plaque and saliva correlates with tumor T staging. Dental plaque microbiota shows higher specialization, especially in poorly differentiated tumors. Both microbiota types become more stable with advanced T staging. Genomic analysis reveals increased virulence factors in poorly differentiated stages.Subsequently, functional pathway analysis and tracing of pathogens reveal specific microbial mechanisms in oral cancer pathogenesis. Certain oral pathogens may promote tumorigenesis by secreting factors like GAPDH (glyceraldehyde-3-phosphate dehydrogenase), GspG (a gingipain precursor), and AllS (a lysine-specific gingipain precursor).<br><br>CONCLUSIONS: OSCC progression is associated with altered microbial composition, diversity, and genomic profiles in saliva and dental plaque. Poorly differentiated stages show higher abundance of pathogens and virulence factors, implicating them in tumorigenesis.<br><br>CLINICAL RELEVANCE: Understanding the microbial and genomic changes in saliva and dental plaque during OSCC progression could aid in developing new diagnostic biomarkers and targeted therapies, potentially enhancing early detection, treatment efficacy, and patient prognosis. Maintaining oral microbiota homeostasis may also help prevent oral cancer.}, }
@article {pmid40420833, year = {2025}, author = {Clasen, F and Yildirim, S and Arıkan, M and Garcia-Guevara, F and Hanoğlu, L and Yılmaz, NH and Şen, A and Celik, HK and Neslihan, AA and Demir, TK and Temel, Z and Mardinoglu, A and Moyes, DL and Uhlen, M and Shoaie, S}, title = {Microbiome signatures of virulence in the oral-gut-brain axis influence Parkinson's disease and cognitive decline pathophysiology.}, journal = {Gut microbes}, volume = {17}, number = {1}, pages = {2506843}, doi = {10.1080/19490976.2025.2506843}, pmid = {40420833}, issn = {1949-0984}, mesh = {Humans ; *Parkinson Disease/microbiology/physiopathology ; *Cognitive Dysfunction/microbiology/physiopathology ; *Gastrointestinal Microbiome ; *Mouth/microbiology ; *Brain/physiopathology/microbiology ; Male ; Female ; Aged ; *Bacteria/genetics/classification/pathogenicity/isolation &amp; purification ; Metagenomics ; Virulence ; Virulence Factors/genetics/metabolism ; Saliva/microbiology/chemistry ; Middle Aged ; }, abstract = {The human microbiome is increasingly recognized for its crucial role in the development and progression of neurodegenerative diseases. While the gut-brain axis has been extensively studied, the contribution of the oral microbiome and gut-oral tropism in neurodegeneration has been largely overlooked. Cognitive impairment (CI) is common in neurodegenerative diseases and develops on a spectrum. In Parkinson's Disease (PD) patients, CI is one of the most common non-motor symptoms but its mechanistic development across the spectrum remains unclear, complicating early diagnosis of at-risk individuals. Here, we generated 228 shotgun metagenomics samples of the gut and oral microbiomes across PD patients with mild cognitive impairment (PD-MCI) or dementia (PDD), and a healthy cohort, to study the role of gut and oral microbiomes on CI in PD. In addition to revealing compositional and functional signatures, the role of pathobionts, and dysregulated metabolic pathways of the oral and gut microbiome in PD-MCI and PDD, we also revealed the importance of oral-gut translocation in increasing abundance of virulence factors in PD and CI. The oral-gut virulence was further integrated with saliva metaproteomics and demonstrated their potential role in dysfunction of host immunity and brain endothelial cells. Our findings highlight the significance of the oral-gut-brain axis and underscore its potential for discovering novel biomarkers for PD and CI.}, }
@article {pmid40418963, year = {2025}, author = {Tyson-Carr, J and Leng, J and Scott, M and Adams, S and Hoptroff, M and Murphy, B and Fallon, N and Paterson, S and Thomas, A and Giesbrecht, T and Roberts, C}, title = {Body-site specific associations between human skin microbiome composition and psychological wellbeing.}, journal = {The British journal of dermatology}, volume = {}, number = {}, pages = {}, doi = {10.1093/bjd/ljaf177}, pmid = {40418963}, issn = {1365-2133}, abstract = {BACKGROUND/OBJECTIVES: There is increasing scientific interest in understanding the interplay between psychological wellbeing and the human microbiome, with a particular focus on the gut microbiome's impact on psychological health. However, the role of the skin microbiome remains underexplored. The current study addresses this gap by investigating the relationship between the human skin microbiome at various body sites (face, scalp, forearm, axilla) and psychological wellbeing. This unique multi body site investigation aims to provide an understanding of the skin microbiome's role in psychological health.<br><br>METHODS: Fifty-three participants underwent microbiome sampling via skin swabbing from four body regions (forearm, face, scalp, and axilla) and completed psychological measures of global/general wellbeing (Affect Grid, Sleep Quality, Stress NRS-11, PSS-10) and body site-related wellbeing (Hair &amp; ScalpCARE, SkinCARE, UnderarmCARE). All bacterial DNA extracts were analysed using quantitative polymerase chain reaction (qPCR) and Illumina sequencing of the V1 - V2 region of the 16S gene. Microbial diversity was computed as Shannon diversity and Faith's Phylogenetic diversity. Correlations were determined between psychological measures, microbial diversity, and genera for each body site.<br><br>RESULTS: The current study uncovered that specific bacterial genera were associated with aspects of wellbeing. Specifically, Cutibacterium showed consistent associations with psychological wellbeing across multiple body locations. Key findings showed increased Cutibacterium on the face and axilla was associated with reduced stress, increased Cutibacterium in the axilla was associated with increased mood pleasantness.<br><br>CONCLUSIONS: These findings highlight, for the first time, the nuanced relationship between skin microbiome and psychological wellbeing. Increased Cutibacterium across multiple body-sites was consistently associated with positive wellbeing outcomes. This underscores the need for further investigation into specific bacterial taxa that may be involved in a skin-brain axis, as well as the importance of specific microbial communities on the body and their potential influence on this connection.}, }
@article {pmid40417982, year = {2025}, author = {Brown, SE and He, X and Magder, L and Johnston, ED and Morgan, D and Ravel, J and Mark, K and Ghanem, KG and Brotman, RM}, title = {Bacterial vaginosis incidence following a single hyperosmolal vaginal lubricant exposure: A comparison of two observational cohorts.}, journal = {Sexually transmitted diseases}, volume = {}, number = {}, pages = {}, doi = {10.1097/OLQ.0000000000002184}, pmid = {40417982}, issn = {1537-4521}, abstract = {BACKGROUND: Hyperosmolal lubricants may negatively affect the vaginal microenvironment, increasing the risk for bacterial vaginosis (BV). We compared the incidence of Amsel-defined BV in reproductive-age women exposed to hyperosmolal lubricant during transvaginal ultrasound to those without recent lubricant exposure.<br><br>METHODS: We analyzed two observational cohorts over 10 weeks: 58 lubricant-exposed women from the Gynecology and Lubricants Effects study and 59 lubricant-unexposed women from a University of Alabama Birmingham cohort linked to the University of Maryland Human Microbiome Project. BV was diagnosed using Amsel criteria at baseline, mid-study (lubricant-exposed: week 2, lubricant-unexposed: week 5), and final visit (week 10), and categorized by symptomatology. Risks for incident BV and Amsel criteria were assessed using modified Poisson regression with robust standard errors. An additional outcome of new-onset/newly-symptomatic BV included those with baseline asymptomatic BV. A secondary analysis focused on Black participants (N = 73) due to an observed higher BV incidence.<br><br>RESULTS: Baseline demographics and behaviors were similar between the cohorts. Among all participants, lubricant was not associated with new-onset BV (adjusted relative risk (aRR):1.32, 95% CI:0.58-3.01). 88% (23/26) of all new-onset/newly-symptomatic BV cases occurred in Black participants. Among Black participants, exposure to lubricant doubled the risk of developing new-onset BV (aRR:2.18, 95% CI:1.16-4.11) and new-onset/newly-symptomatic BV (aRR:1.91, 95% CI: 1.04-3.51), and increased the risk for new-onset clue cells (aRR:2.18, 95% CI:1.17 - 4.06) versus no lubricant exposure.<br><br>CONCLUSION: Hyperosmolal lubricants was associated with BV incidence in Black women. Factors contributing to this elevated risk require further research.}, }
@article {pmid40415928, year = {2025}, author = {Karimianghadim, R and Satokari, R and Yeo, S and Arkkila, P and Kao, D and Pakpour, S}, title = {Prolonged effect of antibiotic therapy on the gut microbiota composition, functionality, and antibiotic resistance genes' profiles in healthy stool donors.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1589704}, pmid = {40415928}, issn = {1664-302X}, abstract = {INTRODUCTION: Fecal microbiota transplantation (FMT) is highly effective in preventing Clostridioides difficile recurrence by restoring gut microbiota composition and function. However, the impact of recent antibiotic use, a key exclusion criterion for stool donors, on gut microbiota recovery is poorly understood.<br><br>METHODS: We investigated microbial recovery dynamics following antibiotic use in three long-term stool donors from Canada and Finland. Using longitudinal stool sampling, metagenomic sequencing, and qPCR, we assessed changes in bacterial diversity, community composition, microbial functions, the gut phageome, and the risk of transmitting antibiotic-resistant genes (ARGs).<br><br>RESULTS: Antibiotics caused lasting disruption to bacterial communities, significantly reducing important taxa like Bifidobacterium bifidum, Blautia wexlerae, Akkermansia muciniphila, Eubacterium sp. CAG 180, and Eubacterium hallii, with effects persisting for months. Functional analyses revealed alterations in housekeeping genes critical for energy production and biosynthesis, with no direct links to key health-related pathways. Antibiotics also disrupted viral populations, decreasing diversity and increasing crAssphage abundance, reflecting disrupted host-bacteriophage dynamics. No significant increase in clinically important ARGs was detected.<br><br>DISCUSSION: These findings highlight the unpredictable and complex recovery of gut microbiota post-antibiotics. Individualized suspension periods in donor programs, guided by metagenomic analyses, are recommended to optimize FMT outcomes in various indications by considering antibiotic spectrum, duration, and host-specific factors.}, }
@article {pmid40414632, year = {2025}, author = {Srinivasan, S}, title = {Disruption in the human microbiome causing behavioural changes in bipolar disorder.}, journal = {International review of neurobiology}, volume = {180}, number = {}, pages = {157-187}, doi = {10.1016/bs.irn.2025.04.001}, pmid = {40414632}, issn = {2162-5514}, mesh = {Humans ; *Bipolar Disorder/microbiology/physiopathology/psychology ; *Gastrointestinal Microbiome/physiology ; *Microbiota/physiology ; }, abstract = {This chapter explores the intriguing and complex relationship between the human microbiome and Bipolar Disorder (BD). The microbiome, notably the gut microbiota, has been increasingly recognised as a key performer in brain health and disease. This is due to its role in the gut-brain axis, a bidirectional communication between the gastrointestinal tract and the central nervous system. Disruptions in the gut microbiota due to factors such as diet, and stress, may influence this axis and potentially trigger or exacerbate psychiatric conditions. Hence, we investigate into the present interpretation of the microbiome's role in mental health, concentrating on its impact on mood regulation and cognitive function. Consequently, we also explore the possible mechanisms through which microbiome disruption may pay to the behavioural changes observed in BD. Further exploration understand the complex interplay between the microbiome and BD and translate these findings into effective therapeutic plans.}, }
@article {pmid40414631, year = {2025}, author = {Krishnan, D and Ghosh, P and Lakshman, N and Justin, A and Ramasamy, S}, title = {Oro-pharyngeal mucosal microbiome alternations causing immune system dysregulation in schizophrenia.}, journal = {International review of neurobiology}, volume = {180}, number = {}, pages = {125-156}, doi = {10.1016/bs.irn.2025.03.003}, pmid = {40414631}, issn = {2162-5514}, mesh = {Humans ; *Schizophrenia/immunology/microbiology ; *Microbiota/immunology/physiology ; *Oropharynx/microbiology/immunology ; *Mouth Mucosa/microbiology/immunology ; }, abstract = {Schizophrenia is a chronic and thoughtful psychological disorder that affects a person's thinking, feelings, and behaviours. Multi-factorial genetic, environmental, and neurological variables cause it. Recently, more research focused on the human microbiome, which alters the immune system and develops adverse health effects on the human body. The study discusses a possible relationship between the oropharyngeal microbiome and schizophrenia. According to recent studies, the oropharyngeal microbiome may alter the immune system in the human body and cause various psychiatric disorders, including schizophrenia. The oropharyngeal microbiome can cause schizophrenia either by affecting the genes, chromosomes, and immune system in the human body. Additionally, it examines the combined mechanism of how the oropharyngeal microbiome's alterations lead to genetic abnormalities and immune dysregulation in schizophrenia. By combining the various approaches, this chapter offers a comprehensive view of the oropharyngeal microbiome's role in schizophrenia and suggests that microbial alterations could serve as biomarkers or therapeutic targets for the disorder.}, }
@article {pmid40411603, year = {2025}, author = {Georgakis, N and Premetis, GE and Pantiora, P and Varotsou, C and Bodourian, CS and Labrou, NE}, title = {The impact of metagenomic analysis on the discovery of novel endolysins.}, journal = {Applied microbiology and biotechnology}, volume = {109}, number = {1}, pages = {126}, pmid = {40411603}, issn = {1432-0614}, support = {4036//HFRI/ ; }, mesh = {*Metagenomics/methods ; *Endopeptidases/genetics/isolation &amp; purification/pharmacology/metabolism ; Bacteriophages/enzymology/genetics ; Anti-Bacterial Agents/pharmacology ; Computational Biology ; Humans ; }, abstract = {Metagenomics has revolutionized enzyme discovery by enabling the study of genetic material directly from environmental samples, bypassing the need for microbial cultivation. This approach is particularly effective for identifying novel endolysins, phage-derived enzymes with antibacterial properties suited for therapeutic and industrial applications. Diverse ecosystems, such as biofilms, human microbiome, hot springs, and geothermal areas, serve as rich reservoirs for endolysins with traits like thermostability, broad-spectrum activity, specificity and resistance to harsh conditions. Functional metagenomics, complemented by bioinformatics, enables the discovery and annotation of previously uncharacterized endolysins. Examples of endolysins discovered from metagenomics analysis are discussed. Despite the challenges of analyzing complex microbial ecosystems and isolating target genes, metagenomics holds immense potential for uncovering innovative endolysins, paving the way for developing new biotechnological applications. KEY POINTS: • Endolysins offer antibacterial potential for therapeutic and industrial use. • Metagenomics enables discovery of novel endolysins from diverse ecosystems. • Advances in tools and methods have accelerated novel endolysins discovery.}, }
@article {pmid40411594, year = {2025}, author = {Dash, HR and Patel, A}, title = {Genealogically bewildered individuals and forensic identification: a review of current and emerging solutions.}, journal = {International journal of legal medicine}, volume = {}, number = {}, pages = {}, pmid = {40411594}, issn = {1437-1596}, abstract = {The increasing use of assisted reproductive technologies (ART) with donor gametes is driven by rising infertility rates, delayed parenthood, and the need to prevent hereditary diseases. Greater social acceptance of diverse family structures, advancements in reproductive medicine, and improving success rates also contribute. Accessibility, affordability, and cross-border reproductive care further expand ART's reach, making donor gametes a preferred option for many individuals and couples worldwide. The widespread application of ART has led to an increasing number of donor-conceived individuals, many of whom are now reaching reproductive maturity. This demographic shift introduces significant challenges for traditional forensic genetic identification methods, which rely on biological reference samples from genetically related individuals. The absence of such samples complicates the identification process, particularly for individuals conceived via gamete donation or adoption, where biological and legal parentage are incongruent. Conventional forensic genetic analyses, including short tandem repeat (STR) and single nucleotide polymorphism (SNP) profiling of autosomal, Y-chromosome, X-chromosome, and mitochondrial DNA, exhibit limited efficacy in these scenarios. While these methods can sometimes identify individuals conceived using a single donor gamete, they are insufficient for cases involving dual donor gametes or mitochondrial replacement therapy. Emerging methodologies such as forensic genetic genealogy, DNA methylation profiling, and human microbiome analysis offer innovative approaches but necessitate further clinical validation and standardization.}, }
@article {pmid40409390, year = {2025}, author = {Mlangeni, T and Jian, C and Häkkinen, HK and de Vos, WM and Salonen, A and Kantele, A}, title = {Travel to the tropics: Impact on gut microbiota.}, journal = {Travel medicine and infectious disease}, volume = {}, number = {}, pages = {102869}, doi = {10.1016/j.tmaid.2025.102869}, pmid = {40409390}, issn = {1873-0442}, abstract = {BACKGROUND: Visitors to low- and middle-income countries (LMICs) encounter numerous new intestinal microbes, including diarrhoeal pathogens and multidrug-resistant (MDR) bacteria, such as extended-spectrum β-lactamase-producing Enterobacterales (ESBL-PE). Consequently, many develop travellers' diarrhoea (TD) and/or become colonised by ESBL-PE. We explored the impact of LMIC travel, TD, and ESBL-PE/diarrheal pathogen colonisation on gut microbiota.<br><br>METHODS: The present study included 92 participants from the clinical vaccine trial OEV123, who spent 12 days in Benin, West Africa, and provided exploratory pre- and post-travel stool samples. The samples were subjected to quantitative polymerase chain reaction (qPCR) to detect diarrhoeal pathogens and 16S rRNA gene amplicon sequencing for microbiota profiling.<br><br>RESULTS: Travel significantly altered gut microbiota, showing reduced richness, decreased &#x3b1;-diversity, and a 40-fold increase in Escherichia/Shigella. qPCR detected diarrhoeagenic Escherichia coli (DEC) in post-travel stools of 89% of the 92 participants. No specific microbiota signatures were linked to TD or ESBL-PE acquisition. Participants acquiring multiple DEC pathotypes had higher pre-travel levels of Ruminococcaceae and Coprococcus spp., while their post-travel microbiota was enriched with oxygen-tolerant and oral- and upper gastrointestinal-associated taxa.<br><br>CONCLUSION: Travel to an LMIC significantly impacted intestinal microbiota. Individuals with high pre-travel proportions of Ruminococcaceae and Coprococcus spp. acquired a greater DEC pathotype diversity. However, no specific pre-travel microbiota profile was identified as protective against or predisposing to TD or acquisition of MDR bacteria.}, }
@article {pmid40409379, year = {2025}, author = {Meesters, LD and Roubroeks, JAY and Gerritsen, A and Velthuijs, N and Klijnhout, JA and Laberthonnière, C and van Vlijmen-Willems, IM and Hübenthal, M and Rodijk-Olthuis, D and Peters, RHW and Rikken, G and Szymczak, S and Fyhrquist, N and Alenius, H and Weidinger, S and Smits, JPH and Mhlanga, M and Zhou, H and Niehues, H and van den Bogaard, EH}, title = {Dissecting key contributions of Th2 and Th17 cytokines to atopic dermatitis pathophysiology.}, journal = {The Journal of allergy and clinical immunology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jaci.2025.05.007}, pmid = {40409379}, issn = {1097-6825}, abstract = {BACKGROUND: In atopic dermatitis (AD), epidermal disease hallmarks are driven by a complex cutaneous inflammatory milieu that varies between patients. How these variable inflammatory signals affect cellular and molecular epidermal AD phenotypes is difficult to study in vivo.<br><br>OBJECTIVE: We aimed to unravel which AD-associated cytokines drive specific epidermal disease hallmarks.<br><br>METHODS: We utilized primary and immortalized keratinocyte-derived human epidermal equivalents stimulated with T helper (Th)2, -17 and -22 cytokines.<br><br>RESULTS: Morphological, functional and transcriptomic analyses revealed that Th2 cytokines interleukin (IL)-4 and IL-13 were main inducers of a pro-inflammatory and hyperproliferative epidermis. The presence of IL-17A or IL-22 in the Th2 milieu, and especially Th2 + IL-22, most closely resembled AD hallmarks including spongiosis, more severe keratinocyte differentiation defects and epidermal barrier dysfunction. Single-cell spatial transcriptomics showed expansion of keratinocytes expressing high levels of proliferation genes, and downregulation of differentiation genes in the upper epidermal layers. The transcriptomic comparison to in vivo AD lesional skin indicated that the Th2 + IL-22 AD model demonstrated greatest resemblance and identified AD disease marker genes altered by Th2 + IL-22 such as downregulated ACER1 and AKR1C3. Gene expression levels were restored by combinatory exposure to aryl hydrocarbon receptor (AHR) ligand tapinarof and Janus Kinase (JAK) inhibitor tofacitinib. This combined therapeutic approach also completely restored epidermal barrier function and improved morphological disease hallmarks.<br><br>CONCLUSION: Our results reveal the important role of IL-22 in the Th2 driven acute AD pathophysiology and highlight the potential of combinatory medicine in targeted treatment of AD.}, }
@article {pmid40401972, year = {2025}, author = {Pitek, AP and Daisley, BA and Chmiel, JA and Chernyshova, AM and Dhami, G and Reid, G and Thompson, GJ}, title = {Probiotic effects on ectoparasitic mite infestations in honey bees (Apis mellifera) are modulated by environmental conditions and route of administration.}, journal = {Microbiology spectrum}, volume = {}, number = {}, pages = {e0249824}, doi = {10.1128/spectrum.02498-24}, pmid = {40401972}, issn = {2165-0497}, abstract = {Beneficial bacteria can improve the health of managed honey bees (Apis mellifera) via immune system support as well as direct inhibition of pathogens. However, our understanding of how environmental factors and delivery methods impact treatment outcomes is limited. Here, we evaluated how supplementation of a three-strain lactobacilli consortium (Lactiplantibacillus plantarum Lp39, Apilactobacillus kunkeei BR-1, and Lacticaseibacillus rhamnosus; LX3) affects ectoparasitic mite (Varroa destructor) and bacterial (Paenibacillus larvae) load. We measured this effect following delivery of LX3 in either edible (protein patty) or topical (spray) forms and did so across three distinct habitats (forage-rich, agricultural, and urban). Results demonstrate significant control of mite infestation levels following patty delivery, relative to untreated patty controls. Spray methods, by contrast, were ineffective. Specifically, a control group that received only an uninoculated patty carried more mites than any other group, suggesting excess protein within hives is a catalyst for mite proliferation. This effect, whereby the excess-protein group had the highest parasite load, was pronounced in the most natural (forage-rich) environment type, indicating a significant site-by-treatment interaction. No influence of LX3 on P. larvae loads was observed in the asymptomatic colonies studied, which is likely attributable to the already low levels of pathogenic spores present and challenges associated with detection limits. In summary, this multi-site field study suggests that an LX3-infusion of standard protein patties is an effective method to control Varroa destructor infestations in commercial honey bee colonies.IMPORTANCECommercial beekeeping operations typically have a narrow profit range that depends on maintaining healthy hives throughout the season. Unfortunately, parasitic Varroa mites and bacterial pathogens can contribute to colony losses. The plight of honey bees can in turn affect the price and availability of produce on the agri-food market. There is therefore a need for innovation in the beekeeping industry to help secure bee livestock from season to season. One relatively new approach to sustainable beekeeping is the use of beneficial bacterial supplements that beekeepers can feed to or otherwise apply to hives in aid of the bee's natural health and abilities as mediated through their gut-brain axis. Our multi-site field study applies this approach. We find that a pollen protein patty is an effective vehicle for delivering probiotic bacteria to commercial honey bee colonies and for helping to keep Varroa destructor infestation levels in check.}, }
@article {pmid40398637, year = {2025}, author = {Alaguthevar, R and Pawale, AV and Murugesan, B and Khan, A and Rhim, JW and Chelladurai, D}, title = {Comprehensive Review of Food Archaeome: Exploring the Understudied Microbiome and Health Benefits of Fermented Foods.}, journal = {Microbial pathogenesis}, volume = {}, number = {}, pages = {107718}, doi = {10.1016/j.micpath.2025.107718}, pmid = {40398637}, issn = {1096-1208}, abstract = {Extremophiles are species that thrive optimally in extreme environmental conditions, and advances in DNA-based identification methods have sparked increased interest in studying the dynamic ecosystem of archaea outside their harsh environmental niches. Most studies on the food microbiome have primarily focused on bacterial and fungal communities. In contrast, food archaea play an essential role in human-related foods, despite being largely ignored and understudied. Archaea can survive, colonize, and thrive under harsh processing conditions in food manufacturing, and they can enter the human body and modulate the human microbiome. Additionally, gut microbiomes can be influenced through vertical transmission facilitated by breast milk, organic animal products, and salty fermented foods. Early studies on foods concentrated mostly on salty and fermented items because these foods represent extreme environments. However, gut-associated archaea may be linked to disease as they produce toxic compounds and detoxify pathogen growth inhibitors. The precise mechanisms by which this pathogenicity occurs are still unknown, and further studies are necessary to illuminate potential human health implications. Despite the growing understanding of the prevalence of archaeal pathogens in extreme environments, current research on food-related archaeal communities remains limited. This review emphasizes the role of food archaeal pathogens in human health and describes new technologies for producing novel nutritious foods utilizing archaeal-derived materials in the food industry.}, }
@article {pmid40396735, year = {2025}, author = {Zhang, J and Chen, B-Y and Zhi, M-F and Lin, W-Z and Li, Y-L and Ye, H-L and Xu, S and Zhu, H and Zhou, L-J and Du, L-J and Meng, X-Q and Liu, Y and Feng, Q and Duan, S-Z}, title = {Linking oral microbiota to periodontitis and hypertension unveils that Filifactor alocis aggravates hypertension via infiltration of interferon-γ[+] T cells.}, journal = {mSystems}, volume = {}, number = {}, pages = {e0008425}, doi = {10.1128/msystems.00084-25}, pmid = {40396735}, issn = {2379-5077}, abstract = {UNLABELLED: Periodontal disease (PD), an inflammatory disease initiated by oral microbiota, may aggravate hypertension (HTN). Few studies were employed to characterize the oral microbiota in hypertensive patients with periodontitis. To investigate the interplay between oral microbiota and hypertension in individuals with periodontitis, we initiated a metagenomic sequencing study on subgingival plaque and saliva samples sourced from HTN patients and those with hypertension and periodontitis (PDHTN). Our primary objective was to characterize species serving as pivotal links (bridge species) in exacerbating hypertension induced by periodontal disease. Within subgingival plaque and saliva specimens, we pinpointed 31 and 28 bridge species, respectively. Furthermore, we noted a decrease in the abundance of nitrate-reducing bacteria, such as Actinomyces spp., Rothia spp., and Veillonella spp., in PDHTN samples. Employing network analysis, we distinguished distinct polymicrobial clusters within the two patient groups. These bridge species coalesced into polymicrobial clusters, revealing intricate symbiotic and competitive relationships. To substantiate our findings, we leveraged an angiotensin II-infused animal model of ligature-induced periodontitis (LIP), confirming the contributory role of Filifactor alocis-a selectively analyzed subgingival bridge species-in exacerbating hypertension and upregulating the frequency of renal CD4[+]IFNγ[+] and CD8[+]IFNγ[+] T cells. Our study screened a list of species linking PD and HTN. PD may aggravate HTN by decreasing the abundance of nitrate-reducing bacteria and increasing the abundance of pathogens. Using an animal model, we demonstrated that F. alocis aggravates HTN via the accumulation of IFNγ[+] T cells in the kidneys.<br><br>IMPORTANCE: Both periodontal disease and hypertension are widely prevalent all over the world. PD may aggravate the development of HTN via oral microbiota. However, few studies were employed to characterize the oral microbiota in hypertensive patients with periodontitis. Here, the present study profiled the oral microbiota in hypertensive participants with periodontitis. We found that the depleted abundance of nitrate-reducing bacteria and the enriched abundance of pathogens. Finally, we validated the role of Filifactor alocis in exacerbating HTN via infiltration of IFN&#x3b3;[+] T cells in mice kidneys. Our study improved the understanding of oral microbiota linking PD and HTN.}, }
@article {pmid40386394, year = {2025}, author = {Chiu, CJ and Chiu, E and Chang, ML}, title = {Interaction between Infection of Porphyromonas gingivalis, A Keystone Microbe of Oral Microbiome, and Serum Levels of Lutein/Zeaxanthin Is Associated with Risk for Age-related Macular Degeneration.}, journal = {Research square}, volume = {}, number = {}, pages = {}, doi = {10.21203/rs.3.rs-6188207/v1}, pmid = {40386394}, issn = {2693-5015}, abstract = {Porphyromonas gingivalis (P. gingivalis) functions as a catalyst bacterium in the development of periodontitis, and the serum antibody level against P. gingivalis is considered a surrogate marker for the activity level of periodontopathic microbiome. The chronic systemic inflammation induced by P. gingivalis elevates the risk of various systemic and neurodegenerative disorders, including atherosclerosis, diabetes, and Alzheimer's disease. Although the connection between human microbiome and age-related macular degeneration (AMD) remains relatively unexplored, it is noteworthy that AMD shares risk factors and etiological mechanisms with diseases related to P. gingivalis . To investigate the potential association between periodontopathic microbiome and AMD occurrence, we conducted a candidate microbe approach case-control study. Our hypothesis was tested by examining the correlation between serum P. gingivalis immunoglobulin G (IgG) levels and AMD. Comparing the lowest IgG category (≤ 57 enzyme-linked immunosorbent assay units (EU)) with higher categories revealed escalating risks: the second higher category (58-65 EU) conferred almost a 30% increased risk (odds ratio (OR) = 1.28, 95% confidence interval (CI): 1.17 to 1.4), the third higher category (66-119 EU) conferred nearly a 60% increase (OR = 1.58, 95% CI: 1.46 to 1.72), and the highest category (> 119 EU) conveyed over a two-fold risk (OR = 2.04, 95% CI: 1.62 to 2.58) of early AMD. Aligning with the notion that the microbiome composition is significantly shaped by the host's diet, our analysis indicates that sustaining elevated serum levels of lutein/zeaxanthin (≥ 0.35 µmol/L or ≥ 20 µg/dL) might potentially mitigate the P. gingivalis -related AMD risk by as much as 35% (P for interaction < 0.0001). Although the precise mechanism requires additional exploration, these findings suggest a connection between nutrition and oral microbiome, emphasizing their collective role in maintaining eye health.}, }
@article {pmid40381618, year = {2025}, author = {Kim, M and Kim, J and Lee, GS and Olinares, PDB and Airan, Y and Chow, JL and Park, J and Jeong, Y and Park, J and Chait, BT and Herzon, SB and Kim, CS and Kang, JY}, title = {Structural study on human microbiome-derived polyketide synthases that assemble genotoxic colibactin.}, journal = {Structure (London, England : 1993)}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.str.2025.04.017}, pmid = {40381618}, issn = {1878-4186}, abstract = {Colibactin, a human microbiome-derived genotoxin, promotes colorectal cancer by damaging the host gut epithelial genomes. While colibactin is synthesized via a hybrid non-ribosomal peptide synthetase (NRPS)-polyketide synthase (PKS) pathway, known as pks or clb, the structural details of its biosynthetic enzymes remain limited, hindering our understanding of its biosynthesis and clinical application. In this study, we report the cryo-EM structures of two colibactin-producing PKS enzymes, ClbC and ClbI, captured in different reaction states using a substrate-mimic crosslinker. Our structural analysis revealed the binding sites of carrier protein (CP) domains of the ClbC and ClbI on their ketosynthase (KS) domains. Further, we identified a novel NRPS-PKS docking interaction between ClbI and its upstream enzyme, ClbH, mediated by the C-terminal peptide ClbH and the dimeric interface of ClbI, establishing a 1:2 stoichiometry. These findings advance our understanding of colibactin assembly line and provide broader insights into NRPS-PKS natural product biosynthesis mechanisms.}, }
@article {pmid40381485, year = {2025}, author = {Hartjes, ED and Lim, YJ and Velenosi, TJ and Al, KF and Macklaim, JM and Kucey, AS and Reid, G and Burton, JP and Gloor, GB and Urquhart, BL}, title = {The impact of progressive chronic kidney disease on hepatic drug metabolism.}, journal = {Drug metabolism and disposition: the biological fate of chemicals}, volume = {53}, number = {6}, pages = {100085}, doi = {10.1016/j.dmd.2025.100085}, pmid = {40381485}, issn = {1521-009X}, abstract = {Nonrenal clearance pathways such as drug metabolism are decreased in severe chronic kidney disease (CKD). The impact of progression of CKD on hepatic drug metabolism is unknown. We characterized the effect of progressive CKD on hepatic cytochrome P450 expression and evaluated dysbiosis and uremia as kidney function declined. Rats fed control or CKD-inducing adenine diet were studied at 5 time points over 42 days. Cytochrome P450 expression and activity were compared with alterations in the (1) plasma and liver metabolome and (2) gut bacterial microbiota. CYP3A2 and CYP2C11 were downregulated in CKD by ≥76% (P < .001) concurrently with or slightly prior to CKD onset as defined by serum creatinine. Metabolite profiles were altered prior to changes in the gut microbiota, and gut-derived uremic toxins including indoxyl sulfate, phenyl sulfate, and 4-ethylphenyl sulfate correlated with CYP3A2 or CYP2C11 expression. Bacterial genera Turicibacter and Parabacteroides were identified as being characteristic of CKD. In conclusion, CYP3A2 and CYP2C11 are downregulated before dysbiosis and uremia. SIGNIFICANCE STATEMENT: This study describes the effect of progressive kidney disease on hepatic CYP2C11 and CYP3A2 enzyme expression and activity in a rat model of CKD. Expression and activity of drug metabolizing enzymes occurs prior to uremia or dysbiosis.}, }
@article {pmid40378286, year = {2025}, author = {Fields, BD and Pascal, DG and Rando, OK and Huddleston, ME and Ingram, K and Hopton, R and Grogg, MW and Nelson, MT and Voigt, CA}, title = {Design of a Continuous GAA-Producing Probiotic as a Potential Mitigator of the Effects of Sleep Deprivation.}, journal = {ACS synthetic biology}, volume = {}, number = {}, pages = {}, doi = {10.1021/acssynbio.4c00690}, pmid = {40378286}, issn = {2161-5063}, abstract = {Creatine is a popular athletic supplement that has also been shown to improve cognitive performance upon sleep deprivation. However, it is rapidly cleared from the gastrointestinal tract a few hours after consumption. Toward providing a persistent creatine dose, we engineered the human probiotic Escherichia coli Nissle (EcN) to produce guanidinoacetic acid (GAA), which is converted to creatine in the liver. We find GAA-producing enzymes present in the human microbiome and compare their activities to known enzymes. Three copies of arginine:glycine amidinotransferase (AGAT) from Actinokineospora terrae are expressed from the genome, and native gcvP, argR, and argA are edited or deleted to improve substrate availability without negatively impacting cell viability. A standard EcN dose (10[12] cells) produces 41 ± 7 mg GAA per hour under laboratory conditions. This work demonstrates that a probiotic bacterium can be engineered to produce sustained GAA titers known to impact cognitive performance.}, }
@article {pmid40377870, year = {2025}, author = {Amen, RA and Hassan, YM and Essmat, RA and Ahmed, RH and Azab, MM and Shehata, NR and Elgazzar, MM and El-Sayed, WM}, title = {Harnessing the Microbiome: CRISPR-Based Gene Editing and Antimicrobial Peptides in Combating Antibiotic Resistance and Cancer.}, journal = {Probiotics and antimicrobial proteins}, volume = {}, number = {}, pages = {}, pmid = {40377870}, issn = {1867-1314}, abstract = {The growing crisis of antibiotic resistance and the increasing incidence of cancer have prompted the exploration of innovative approaches, such as gene editing and antimicrobial peptides (AMPs). The human microbiome is integral to various aspects of health, disease, and therapeutic development, influencing metabolic pathways, immune function, and pathogen resistance. Recent advances in gene editing technologies, particularly CRISPR (clustered regularly interspaced short palindromic repeats), have opened new avenues for leveraging the microbiome to address complex medical challenges, including combating multidrug-resistant pathogens and cancer. The microbiome plays a crucial role in combating antibiotic resistance by modulating microbial communities, influencing pathogen survival and susceptibility to treatments. This review explores the microbiome's dynamic role in metabolic regulation, its contribution to cancer management, and how AMPs help maintain homeostasis and exhibit emerging anticancer properties, supported by both preclinical findings and clinical evidence. Additionally, CRISPR-based microbiome engineering offers potential to enhance host-microbiome interactions, optimizing therapeutic outcomes. The integration of microbiome metagenomics and proteomics has led to the discovery of novel AMPs with targeted anticancer effects. Innovative strategies, such as engineered probiotics and CRISPR-based microbiome engineering, present exciting prospects for next-generation therapies. Despite these advances, the translation of microbiome-based therapies into clinical settings remains challenging due to ethical, regulatory, and ecological hurdles. This review underscores the transformative potential of microbiome-based interventions, emphasizing the role of personalized medicine in maximizing therapeutic efficacy. Furthermore, we also address critical research gaps, limitations, and future directions, including optimizing AMP stability, delivery, and bioavailability, as well as overcoming the regulatory and ethical challenges in clinical translation.}, }
@article {pmid40375898, year = {2025}, author = {Xu, C and Zhao, LY and Ye, CS and Xu, KC and Xu, KY}, title = {The application of machine learning in clinical microbiology and infectious diseases.}, journal = {Frontiers in cellular and infection microbiology}, volume = {15}, number = {}, pages = {1545646}, pmid = {40375898}, issn = {2235-2988}, mesh = {Humans ; *Machine Learning ; *Communicable Diseases/diagnosis/microbiology ; *Microbiology ; Artificial Intelligence ; Algorithms ; }, abstract = {With the development of artificial intelligence(AI) in computer science and statistics, it has been further applied to the medical field. These applications include the management of infectious diseases, in which machine learning has created inroads in clinical microbiology, radiology, genomics, and the analysis of electronic health record data. Especially, the role of machine learning in microbiology has gradually become prominent, and it is used in etiological diagnosis, prediction of antibiotic resistance, association between human microbiome characteristics and complex host diseases, prognosis judgment, and prevention and control of infectious diseases. Machine learning in the field of microbiology mainly adopts supervised learning and unsupervised learning, involving algorithms from classification and regression to clustering and dimensionality reduction. This Review explains crucial concepts in machine learning for unfamiliar readers, describes machine learning's current applications in clinical microbiology and infectious diseases, and summarizes important approaches clinicians must be aware of when evaluating research using machine learning.}, }
@article {pmid40371708, year = {2025}, author = {Attaye, I and Bird, JK and Nieuwdorp, M and Gül, S and Seegers, JFML and Morrison, S and Hofkens, S and Herrema, H and Bui, N and Puhlmann, ML and de Vos, WM}, title = {Anaerobutyricum soehngenii improves glycemic control and other markers of cardio-metabolic health in adults at risk of type 2 diabetes.}, journal = {Gut microbes}, volume = {17}, number = {1}, pages = {2504115}, doi = {10.1080/19490976.2025.2504115}, pmid = {40371708}, issn = {1949-0984}, mesh = {Humans ; *Diabetes Mellitus, Type 2/metabolism/microbiology/prevention &amp; control ; Middle Aged ; Male ; Female ; Double-Blind Method ; *Glycemic Control ; Adult ; Glycated Hemoglobin/analysis/metabolism ; Blood Glucose/metabolism ; Aged ; Prediabetic State/therapy ; Biomarkers/blood ; Blood Pressure ; Gastrointestinal Microbiome ; Europe ; }, abstract = {Anaerobutyricum soehngenii (previously Eubacterium hallii) is a butyrate-producing next-generation beneficial microbe generally recognized as safe. Several short-term intervention trials by A. soehngenii L2-7 have shown improvement of insulin sensitivity in prediabetic subjects and type 2 diabetes patients. To determine the long-term cardiometabolic benefits and safety, we performed a 3-month double-blind, randomized placebo-controlled intervention in 98 prediabetic insulin-resistant adults in Europe and U.S. with daily administration of encapsulated cells of A. soehngenii CH-106, a tetracycline-sensitive isogenic derivative of strain L2-7. Compared to placebo, A. soehngenii-treated subjects showed significantly reduced glycemic variability (1% reduction in the coefficient of variation; p = 0.01) and improved glycemic control (6% reduction in the overall net glycemic action-1; p < 0.05), including reduced serum glycated hemoglobin (HbA1c) levels when including the 4-week washout period (1 mmol/mol reduction; p < 0.05). Moreover, diastolic blood pressure was significantly reduced in all A. soehngenii-treated subjects (3 mm Hg; p < 0.05). The study product was well-tolerated and had no effect on the global intestinal microbiota composition, including alpha and beta-diversity, besides an increased abundance of A. soehngenii in the treatment group, indicative of compliance. The U.S. participants, compared to those in Europe, responded best, notably in the oral glucose tolerance tests (15% improvement in the area-under-the curve of plasma glucose levels; p = 0.039) or coefficient of variation (reduction of 3.1%; p < 0.05). This potentially relates to a more severe prediabetic state in U.S. subjects, associated with significantly reduced (1.5-3.5-fold) relative abundance of Bifidobacterium, Coprococcus, Ruminococcus spp. and two-fold increased relative abundance of Lachnoclostridium spp. In conclusion, daily oral supplementation with A. soehngenii was safe and improved various markers of glycemic control, reduced HbA1c levels and diastolic blood pressure, indicating a novel microbiome-based approach to improve cardio-metabolic health in adults at risk for developing type 2 diabetes.Clinical trial reg. no. NCT04529473, clinicaltrials.govSocial media summary 120 characters: Anaerobutyricum soehngenii supplementation improves #cardio-metabolic health in subjects at risk for type 2 #diabetes.}, }
@article {pmid40371158, year = {2025}, author = {Liu, Y and Ning, H and Li, Y and Li, Y and Ma, J}, title = {The microbiota in breast cancer: dysbiosis, microbial metabolites, and therapeutic implications.}, journal = {American journal of cancer research}, volume = {15}, number = {4}, pages = {1384-1409}, pmid = {40371158}, issn = {2156-6976}, abstract = {The human microbiome plays a pivotal role in host health and disease, with emerging evidence underscoring its significant influence on the development and progression of breast cancer. Studies have revealed that dysbiosis in both the gut and breast tissue microbiota is strongly associated with an elevated risk of breast cancer. Distinct microbial profiles have been identified among healthy individuals, patients with benign breast conditions, and those with malignant tumors, with further variations observed across different ethnic groups and breast cancer subtypes. The complex interplay between breast cancer risk factors and microbial populations, coupled with the direct impact of microbial communities and their metabolites on inflammatory pathways and immune responses, underscores the importance of this field. Additionally, the interaction between gut microbiota and therapeutic modalities such as chemotherapy and radiotherapy is of particular interest, as these interactions can significantly influence treatment outcomes, either enhancing or diminishing efficacy. This review explores the effects of the Mediterranean diet, probiotics, prebiotics, and natural medicinal products on gut microbiota, emphasizing their potential as innovative therapeutic strategies. Notably, the use of engineered probiotics within the tumor microenvironment represents a promising frontier in breast cancer treatment. In conclusion, research on the human microbiome not only deepens our understanding of breast cancer pathogenesis but also lays the groundwork for the development of novel and targeted therapeutic interventions.}, }
@article {pmid40370098, year = {2025}, author = {Wang, N and Wu, M and Gu, W and Dai, C and Shao, Z and Subbalakshmi, KP}, title = {MSFT-transformer: a multistage fusion tabular transformer for disease prediction using metagenomic data.}, journal = {Briefings in bioinformatics}, volume = {26}, number = {3}, pages = {}, doi = {10.1093/bib/bbaf217}, pmid = {40370098}, issn = {1477-4054}, support = {JUSRP123035//Fundamental Research Funds for the Central Universities/ ; }, mesh = {*Metagenomics/methods ; Humans ; *Metagenome ; *Computational Biology/methods ; Algorithms ; }, abstract = {More and more recent studies highlight the crucial role of the human microbiome in maintaining health, while modern advancements in metagenomic sequencing technologies have been accumulating data that are associated with human diseases. Although metagenomic data offer rich, multifaceted information, including taxonomic and functional abundance profiles, their full potential remains underutilized, as most approaches rely only on one type of information to discover and understand their related correlations with respect to disease occurrences. To address this limitation, we propose a multistage fusion tabular transformer architecture (MSFT-Transformer), aiming to effectively integrate various types of high-dimensional tabular information extracted from metagenomic data. Its multistage fusion strategy consists of three modules: a fusion-aware feature extraction module in the early stage to improve the extracted information from inputs, an alignment-enhanced fusion module in the mid stage to enforce the retainment of desired information in cross-modal learning, and an integrated feature decision layer in the late stage to incorporate desired cross-modal information. We conduct extensive experiments to evaluate the performance of MSFT-Transformer over state-of-the-art models on five standard datasets. Our results indicate that MSFT-Transformer provides stable performance gains with reduced computational costs. An ablation study illustrates the contributions of all three models compared with a reference multistage fusion transformer without these novel strategies. The result analysis implies the significant potential of the proposed model in future disease prediction with metagenomic data.}, }
@article {pmid40369669, year = {2025}, author = {Purse, C and Parker, A and James, SA and Baker, DJ and Moss, CJ and Evans, R and Durham, J and Funnell, SGP and Carding, SR}, title = {Intestinal microbiota profiles of captive-bred cynomolgus macaques reveal influence of biogeography and age.}, journal = {Animal microbiome}, volume = {7}, number = {1}, pages = {47}, pmid = {40369669}, issn = {2524-4671}, support = {BB/T008717/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; BB/R012490/1//BBSRC/ ; }, abstract = {BACKGROUND: Age-associated changes to the intestinal microbiome may be linked to inflammageing and the development of age-related chronic diseases. Cynomolgus macaques, a common animal model in biomedical research, have strong genetic physiological similarities to humans and may serve as beneficial models for the effect of age on the human microbiome. However, age-associated changes to their intestinal microbiome have previously only been investigated in faecal samples. Here, we have characterised and investigated the effects of age in the cynomolgus macaque intestinal tract in luminal samples from both the small and large intestine.<br><br>RESULTS: Whole metagenomic shotgun sequencing was used to analyse the microbial communities in intestinal content obtained from six different intestinal regions, covering the duodenum to distal colon, of 24 healthy, captive-bred cynomolgus macaques, ranging in age from 4 to 20&#xa0;years. Both reference-based and assembly-based computational profiling approaches were used to analyse changes to intestinal microbiota composition and metabolic potential associated with intestinal biogeography and age. Reference-based computational profiling revealed a significant and progressive increase in both species richness and evenness along the intestinal tract. The microbial community composition also significantly differed between the small intestine, caecum, and colon. Notably, no significant changes in the taxonomic abundance of individual taxa with age were found except when sex was included as a covariate. Additionally, using an assembly-based computational profiling approach, 156 putative novel bacterial and archaeal species were identified.<br><br>CONCLUSIONS: We observed limited effects of age on the composition of the luminal microbiota in the profiled regions of the intestinal tract except when sex was included as a covariate. The enteric microbial communities of the small and the large intestine were, however, distinct, highlighting the limitations of frequently used faecal microbial profiling as a proxy for the intestinal microbiota. The identification of a number of putative novel microbial taxa contributes to knowledge of the full diversity of the cynomolgus macaque intestinal microbiome.}, }
@article {pmid40369630, year = {2025}, author = {Dong, R and Li, M and Gu, XF and Gao, H and Wei, Z and Qi, H and Zhang, J and Feng, Q}, title = {The surface protein Gbp of Fusobacterium nucleatum inhibits osteogenic differentiation by inactivating the Wnt/β-catenin pathway via binding to Annexin A2.}, journal = {Journal of translational medicine}, volume = {23}, number = {1}, pages = {540}, pmid = {40369630}, issn = {1479-5876}, support = {82270980//National Natural Science Foundation of China/ ; 82071122//National Natural Science Foundation of China/ ; the National Clinical Key Specialty (Periodontology) Construction Project//the National Clinical Key Specialty (Periodontology) Construction Project/ ; the National Young Scientist Support Foundation (2019)//the National Young Scientist Support Foundation (2019)/ ; 2021GXRC021//Periodontitis innovation team of Jinan City/ ; 2021SFGC0502//Major Innovation Projects in Shandong Province/ ; 2020KJK001//Oral Microbiome Innovation Team of Shandong Province/ ; 2021ZDSYS18//Shandong Province Key Research and Development Program/ ; }, abstract = {BACKGROUND: Periodontitis is a chronic inflammatory disease that significantly impacts periodontal bone regeneration, yet the distinct biological features of osteoblasts in this condition remain poorly understood. This study aims to elucidate the cellular and molecular mechanisms underlying osteoblast dysfunction in periodontitis, with a focus on the role of Fusobacterium nucleatum (Fn) and its effector protein, D-galactose-binding periplasmic protein (Gbp).<br><br>METHOD: Single-cell RNA sequencing (scRNA-seq) data from human gingival tissues of periodontitis patients (PD) and healthy controls (HC) were analyzed to identify cellular heterogeneity and molecular pathways. An experimental periodontitis model in mice and primary osteoblast cultures were used to investigate the effects of Fn and Gbp on osteogenic differentiation. Transcriptomic analysis, gene set enrichment analysis (GSEA), and protein-protein interaction (PPI) networks were employed to explore the underlying mechanisms.<br><br>RESULTS: scRNA-seq revealed a reduction in mesenchymal stem cells (MSCs) and osteoblastic lineage cells in PD tissues, with significant downregulation of osteogenic pathways such as Wnt signaling. Fn infection induced alveolar bone destruction in vivo and inhibited osteoblast proliferation, differentiation, and mineralization in vitro. Gbp, an Fn adhesin, similarly impaired osteogenic differentiation by downregulating key osteogenic genes and pathways. Transcriptomic analysis identified shared inflammatory and osteogenic pathways affected by Fn and Gbp, with NF-&#x3ba;B signaling activated and Wnt/&#x3b2;-catenin signaling inhibited. Mechanistically, Gbp interacted with the host protein ANXA2, disrupting the ANXA2/GSK3&#x3b2; complex and inhibiting Wnt/&#x3b2;-catenin signaling, a pivotal route for osteoblast differentiation. ANXA2 knockdown mitigated the Fn/Gbp-induced suppression of osteogenic activity, emphasizing its role in Fn-induced bone loss.<br><br>CONCLUSION: This study demonstrates that Fn and its effector Gbp disrupt osteogenic differentiation by inactivating the Wnt/&#x3b2;-catenin pathway binding to ANXA2.}, }
@article {pmid40363959, year = {2025}, author = {Gullo, G and Satullo, M and Billone, V and De Paola, L and Petousis, S and Kotlik, Y and Margioula-Siarkou, C and Perino, A and Cucinella, G}, title = {The Role of the Genital Tract Microbiome in Human Fertility: A Literature Review.}, journal = {Journal of clinical medicine}, volume = {14}, number = {9}, pages = {}, doi = {10.3390/jcm14092923}, pmid = {40363959}, issn = {2077-0383}, abstract = {Background/Objectives: Infertility is a multifactorial condition influenced by various factors, including dysbiosis and alterations in the genital tract microbiome. Recent studies emphasize the microbiome's significant role in influencing a woman's fertility potential, thereby affecting the chances of spontaneous conception and the outcomes of assisted reproductive treatments. Understanding the microbial characteristics and unique features of a healthy genital microbiome, as well as how changes in its composition can impact fertility, would allow for a more comprehensive and personalized approach to managing assisted reproductive treatments. The microbiome also influences pregnancy outcomes, and restoring its balance has been shown to improve fertility in infertile couples. The human microbiome plays a key role in maintaining the body's overall health. Disruptions in microbiome balance among women of reproductive age can contribute to a range of pregnancy-related complications, with notable consequences for both maternal and fetal well-being. Emerging research has highlighted a connection between the reproductive tract microbiome and outcomes of assisted reproductive technologies (ART), suggesting that re-establishing a healthy microbial environment may enhance fertility in couples facing infertility. Methods: We conducted a search on PubMed using the keywords "microbiome", "infertility", and "ART" over the past 10 years. This article aims to provide an updated overview of the role of the microbiome in female reproductive health, with a focus on its implications for fertility treatment. Results: The microbiome has a significant role in influencing women's fertility. Conclusions: Understanding the microbiome's impact on fertility and pregnancy outcomes may lead to more effective and personalized approaches in fertility treatments, improving the chances of successful conception and pregnancy.}, }
@article {pmid40362812, year = {2025}, author = {Cominelli, G and Sulas, F and Pinto, D and Rinaldi, F and Favero, G and Rezzani, R}, title = {Neuro-Nutritional Approach to Neuropathic Pain Management: A Critical Review.}, journal = {Nutrients}, volume = {17}, number = {9}, pages = {}, doi = {10.3390/nu17091502}, pmid = {40362812}, issn = {2072-6643}, support = {Grant donation//Franchini Acciai S.p.A./ ; }, mesh = {Humans ; *Neuralgia/diet therapy/therapy ; *Melatonin/administration &amp; dosage/therapeutic use ; Antioxidants/administration &amp; dosage ; *Pain Management/methods ; Dietary Supplements ; Quality of Life ; *Diet ; Oxidative Stress ; }, abstract = {Pain is a significant global public health issue that can interfere with daily activities, sleep, and interpersonal relationships when it becomes chronic or worsens, ultimately impairing quality of life. Despite ongoing efforts, the efficacy of pain treatments in improving outcomes for patients remains limited. At present, the challenge lies in developing a personalized care and management plan that helps to maintain patient activity levels and effectively manages pain. Neuropathic pain is a chronic condition resulting from damage to the somatosensory nervous system, significantly impacting quality of life. It is partly thought to be caused by inflammation and oxidative stress, and clinical research has suggested a link between this condition and diet. However, these links are not yet well understood and require further investigation to evaluate the pathways involved in neuropathic pain. Specifically, the question remains whether supplementation with dietary antioxidants, such as melatonin, could serve as a potential adjunctive treatment for neuropathic pain modulation. Melatonin, primarily secreted by the pineal gland but also produced by other systems such as the digestive system, is known for its anti-inflammatory, antioxidant, and anti-aging properties. It is found in various fruits and vegetables, and its presence alongside other polyphenols in these foods may enhance melatonin intake and contribute to improved health. The aim of this review is to provide an overview of neuropathic pain and examine the potential role of melatonin as an adjunctive treatment in a neuro-nutritional approach to pain management.}, }
@article {pmid40362760, year = {2025}, author = {Sechi, A and Cedirian, S and Brunetti, T and Quadrelli, F and Torres, F and Tosti, A and Rinaldi, F and Pinto, D and Bolognino, R and Marzano, AV and Piraccini, BM}, title = {Safety First: A Comprehensive Review of Nutritional Supplements for Hair Loss in Breast Cancer Patients.}, journal = {Nutrients}, volume = {17}, number = {9}, pages = {}, doi = {10.3390/nu17091451}, pmid = {40362760}, issn = {2072-6643}, mesh = {Humans ; *Dietary Supplements/adverse effects ; *Breast Neoplasms/therapy/drug therapy/complications ; Female ; *Alopecia/etiology/chemically induced/drug therapy/prevention &amp; control ; Antioxidants/adverse effects/administration &amp; dosage ; Quality of Life ; Vitamin D/adverse effects/administration &amp; dosage ; }, abstract = {Among the distressing side effects of cancer treatments, hair loss is one of the most disturbing for the quality of life and adherence to therapy in breast cancer patients. Many patients take nutritional supplements to prevent hair loss or enhance regrowth. Based on their mechanism and timing of use, nutritional supplements could be divided into safe, cautious, debated, and contraindicated categories. Non-contraindicated supplements generally include safe supplements like vitamin D, which is not known to interfere with cancer treatments. Those that are contraindicated include phytoestrogens and compounds affecting estrogen pathways because of the risk of stimulating tumor growth in cancers sensitive to estrogen. Antioxidants like tocotrienols and resveratrol are given judiciously because of potential interference with cancer therapies dependent on reactive oxygen species. Supplements debated, including nicotinamide, folate, and iron, pose a risk by promoting cellular proliferation or altering the tumor microenvironment. Biotin is nontoxic but interferes with blood test results and is thus difficult in cancer monitoring. Evidence regarding nutritional supplements' safety and efficacy in this context is conflicting. Management by an oncologist is required along with more studies to clearly establish the safety parameters and efficacy guidelines.}, }
@article {pmid40359847, year = {2025}, author = {Liu, S and Ao, C and Li, Z and Chio, LH and Gu, Y and Zhan, H and Li, H and Li, H and Li, Z and Wang, Q}, title = {Development and validation of a polysomnography-based nomogram for predicting amnestic mild cognitive impairment in middle-aged and elderly people.}, journal = {Sleep medicine}, volume = {132}, number = {}, pages = {106564}, doi = {10.1016/j.sleep.2025.106564}, pmid = {40359847}, issn = {1878-5506}, abstract = {BACKGROUND: Amnestic mild cognitive impairment (aMCI) is a subtype of mild cognitive impairment (MCI) that is considered an early stage of Alzheimer's disease (AD). Although early identification of aMCI is crucial for mitigating disease progression, objective and economic evaluation tools designed for aMCI prediction are lacking. Hence, we aimed to develop and validate a novel nomogram based on sleep characteristics to predict the risk of aMCI in middle-aged and elderly adults.<br><br>METHODS: This study included 817 eligible participants who underwent polysomnography (PSG), comprising 339 individuals diagnosed with aMCI. The participants were divided into a training cohort and a validation cohort using a 7:3 random split. Least absolute shrinkage and selection operator (LASSO) regression was employed to identify key predictive factors, followed by multivariable logistic regression to refine the predictors, which were subsequently used to construct a nomogram. The predictive performance of the nomogram was evaluated through receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA).<br><br>RESULTS: Among the 30 potential predictors, 9 independent sleep-related predictors were incorporated into the final nomogram: total sleep time (TST), sleep efficiency (SE), the proportions of nonrapid eye movement stage 1 (N1), nonrapid eye movement stage 3 (N3), and rapid eye movement (REM) sleep, the density and amplitude of fast spindles and the density and amplitude of K-complexes (KCs). The nomogram demonstrated excellent discriminative ability, with an area under the curve (AUC) of 0.968 in the training cohort and 0.953 in the validation cohort. Calibration curves indicated strong agreement between the predicted and observed outcomes, and DCA confirmed the clinical usefulness of the nomogram by showing consistent net benefits across a wide range of threshold probabilities.<br><br>CONCLUSION: In this study, we developed and validated an innovative nomogram based on objective sleep characteristics to predict aMCI risk. By reducing the reliance on subjective or costly diagnostic tools, the nomogram offers a reliable, accessible, and practical method for the early identification of aMCI.}, }
@article {pmid40335149, year = {2025}, author = {Koskenvuo, L and Paajanen, P and Varpe, P and Seppälä, T and Mentula, P and Haapamäki, C and Carpelan-Holmström, M and Carpelan, A and Lehto, K and Satokari, R and Lepistö, A and Sallinen, V}, title = {PROtective ileoStomy versus ProtectivE colostomy in anterior Rectal resectIon: study protocol for a multicenter, open-label, randomised conTrolled studY (PROSPERITY).}, journal = {BMJ open}, volume = {15}, number = {5}, pages = {e096091}, doi = {10.1136/bmjopen-2024-096091}, pmid = {40335149}, issn = {2044-6055}, abstract = {INTRODUCTION: Loop ileostomy and loop colostomy are both used to form a protective stoma after anterior resection. Evidence regarding which of these two procedures is superior is lacking. Furthermore, no studies comparing changes in the microbiome after loop ileostomy or loop colostomy exist.<br><br>METHODS AND ANALYSIS: This multicentre, open-label, superiority, individually randomised controlled trial will include patients who undergo anterior rectal resection with primary anastomosis with a protective stoma. The exclusion criteria are patients who already have a stoma, technical inability to create either type of stoma, aged <18 years and inadequate cooperation. Patients scheduled for anterior rectal resection will be randomised intraoperatively in a 1:1 ratio to undergo either loop ileostomy or loop colostomy. The primary outcome is cumulative stoma-related adverse events within 60 days after primary surgery, measured using the Comprehensive Complication Index (CCI). Secondary outcomes include all postoperative complications (measured using the CCI), number of hospital-free days within 30 days after primary surgery, quality of life at 2 months (measured using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaires-Core 30 and Colorectal 29), complications within 30 days after stoma closure (measured using the CCI) and kidney function (measured using estimated glomerular filtration rate) at 1 year. Tertiary outcomes are survival, kidney function and number of stoma site hernias at 5 years. The sample size was calculated to detect a mean difference of five CCI points between groups, resulting in a final sample size of 350 patients. Microbiome samples will be collected from the faeces and mucous membrane from patients in Helsinki University Hospital.<br><br>ETHICS AND DISSEMINATION: The Ethics Committee of Helsinki University Hospital approved the study (approval number 4579/2024). The findings will be disseminated in peer-reviewed academic journals.<br><br>TRIAL REGISTRATION: ClinicalTrials.gov, NCT06650085, registered on 20 August 2024.<br><br>PROTOCOL VERSION: Version 3.0, dated 17 April 2025.}, }
@article {pmid40333113, year = {2025}, author = {Bordea, MA and Nutz, BTG and Chiorean, AD and Samasca, G and Lupan, I and Simon, LM and Pepelea, L}, title = {Microbial Interactions in Nature: The Impact of Gram-Negative Bacilli on the Hyphal Growth of Candida albicans.}, journal = {Pathogens (Basel, Switzerland)}, volume = {14}, number = {4}, pages = {}, doi = {10.3390/pathogens14040327}, pmid = {40333113}, issn = {2076-0817}, mesh = {*Candida albicans/growth &amp; development/pathogenicity ; Humans ; *Microbial Interactions ; *Hyphae/growth &amp; development ; *Gram-Negative Bacteria/physiology ; Coinfection/microbiology ; *Candidiasis/microbiology ; Virulence ; Microbiota ; }, abstract = {The escalating global prevalence of fungal and bacterial co-infections underscores the significant and multifaceted impact of ubiquitous microorganisms on both environmental equilibria and human well-being. The human microbiome, a complex ecosystem of bacterial communities, harbors opportunistic pathogens capable of inducing superinfections or concurrent infections with Candida spp. The intricate interplay, exemplified by the interaction between Candida albicans and diverse bacteria, necessitates rigorous investigation to elucidate mechanisms by which this polymicrobial behavior potentiates fungal virulence, particularly in immunocompromised individuals. Our study aims to comprehensively examine the ramifications of these interactions, with a specific focus on their influence on fungal virulence and the consequent exacerbation of disease severity. Achieving a comprehensive understanding of these complex relationships is paramount for informing effective clinical management strategies for infectious diseases, and the accurate identification of fungal-bacterial co-infections holds substantial implications for optimizing clinical treatment paradigms, especially in vulnerable immunocompromised hosts.}, }
@article {pmid40330025, year = {2025}, author = {Smail, SW and Albarzinji, N and Salih, RH and Taha, KO and Hirmiz, SM and Ismael, HM and Noori, MF and Azeez, SS and Janson, C}, title = {Microbiome dysbiosis in SARS-CoV-2 infection: implication for pathophysiology and management strategies of COVID-19.}, journal = {Frontiers in cellular and infection microbiology}, volume = {15}, number = {}, pages = {1537456}, pmid = {40330025}, issn = {2235-2988}, mesh = {Humans ; *Dysbiosis/microbiology/therapy ; *COVID-19/microbiology/physiopathology/therapy/complications ; *SARS-CoV-2 ; *Gastrointestinal Microbiome ; }, abstract = {The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiological agent of coronavirus disease 2019 (COVID-19), in late 2019 initiated a global health crisis marked by widespread infection, significant mortality, and long-term health implications. While SARS-CoV-2 primarily targets the respiratory system, recent findings indicate that it also significantly disrupts the human microbiome, particularly the gut microbiota, contributing to disease severity, systemic inflammation, immune dysregulation, and increased susceptibility to secondary infections and chronic conditions. Dysbiosis, or microbial imbalance, exacerbates the clinical outcomes of COVID-19 and has been linked to long-COVID, a condition affecting a significant proportion of survivors and manifesting with over 200 symptoms across multiple organ systems. Despite the growing recognition of microbiome alterations in COVID-19, the precise mechanisms by which SARS-CoV-2 interacts with the microbiome and influences disease progression remain poorly understood. This narrative review investigates the impact of SARS-CoV-2 on host-microbiota dynamics and evaluates its implications in disease severity and for developing personalized therapeutic strategies for COVID-19. Furthermore, it highlights the dual role of the microbiome in modulating disease progression, and as a promising target for advancing diagnostic, prognostic, and therapeutic approaches in managing COVID-19.}, }
@article {pmid40329426, year = {2025}, author = {Ren, L and Yang, J and Xiao, Y and Guo, L and Rao, J and Wu, C and Wang, X and Wang, Y and Zhang, L and Zhang, L and Jiang, X and Zhong, J and Zhong, J and Yang, W and Wang, C and Wang, J and Li, M}, title = {Transmission of the human respiratory microbiome and antibiotic resistance genes in healthy populations.}, journal = {Microbiome}, volume = {13}, number = {1}, pages = {115}, pmid = {40329426}, issn = {2049-2618}, support = {2020-I2M-2-013//Chinese Academy of Medical Sciences (CAMS) Innovation Fund for Medical Sciences (CIFMS)/ ; 2023-I2M-2-001//Chinese Academy of Medical Sciences (CAMS) Innovation Fund for Medical Sciences (CIFMS)/ ; 2023-I2M-2-001//Chinese Academy of Medical Sciences (CAMS) Innovation Fund for Medical Sciences (CIFMS)/ ; 2019PT310029//Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences/ ; 2022YFA1304300//National Key R&amp;D Program of China/ ; 2022YFA1304300//National Key R&amp;D Program of China/ ; NSFC82221004//Foundation for Innovative Research Groups of the National Natural Science Foundation of China/ ; }, abstract = {BACKGROUND: The human microbiome is transmissible between individuals, including pathogens and commensals with metabolic and immune-modulating effects, which could influence susceptibility, severity, and outcomes of both infection and non-infection diseases. However, limited studies of respiratory microbiome transmission within populations have been conducted. Herein, we performed species- and strain-level metagenomic analyses on oropharyngeal (OP) swabs from 1046 healthy urban dwellers across 13 districts, including 111 households with at least two cohabitants, to elucidate the transmission dynamics of the respiratory microbiome within households and communities.<br><br>RESULTS: We found that geographic districts accounted for the greatest variation in the OP microbiome, with unrelated individuals from the same district showing greater microbiome similarity and higher strain-sharing rates than those from different districts. Cohabitants, especially spouses and siblings, exhibited similar microbial abundances and shared more strains, with 16.7% (IQR 0.0-33.3%) of strains shared among cohabitants, compared to 0.0% (IQR 0.0-11.1%) in non-cohabiting pairs (p&#x2009;<&#x2009;0.05). Both respiratory commensals and opportunistic pathogens were shared among cohabitants. In contrast, no evidence of vertical transmission was detected between mother-offspring pairs. Additionally, the OP microbiome contained diverse antibiotic resistance genes (ARGs), with 15.0% linked to mobile genetic elements (MGEs) or plasmids; the flanking sequences of these ARGs were more conserved across species than those of non-MGE-associated ARGs, suggesting horizontal transfer of ARGs among respiratory microorganisms.<br><br>CONCLUSIONS: In summary, we characterized the transmissible nature of the OP microbiome and the risk of ARG dissemination among respiratory microorganisms. These findings underscore the role of respiratory microbes and ARGs exchange in shaping the microbiome of healthy populations and emphasize their relevance to public health strategies for respiratory health management. Video Abstract.}, }
@article {pmid40328944, year = {2025}, author = {Kim, Y and Worby, CJ and Acharya, S and van Dijk, LR and Alfonsetti, D and Gromko, Z and Azimzadeh, PN and Dodson, KW and Gerber, GK and Hultgren, SJ and Earl, AM and Berger, B and Gibson, TE}, title = {Longitudinal profiling of low-abundance strains in microbiomes with ChronoStrain.}, journal = {Nature microbiology}, volume = {10}, number = {5}, pages = {1184-1197}, pmid = {40328944}, issn = {2058-5276}, support = {R35GM143056//U.S. Department of Health &amp; Human Services | National Institutes of Health (NIH)/ ; R21AI154075//U.S. Department of Health &amp; Human Services | National Institutes of Health (NIH)/ ; R35GM149270//U.S. Department of Health &amp; Human Services | National Institutes of Health (NIH)/ ; R01DK121822//U.S. Department of Health &amp; Human Services | National Institutes of Health (NIH)/ ; U19AI110818//U.S. Department of Health &amp; Human Services | National Institutes of Health (NIH)/ ; R35GM141861//U.S. Department of Health &amp; Human Services | National Institutes of Health (NIH)/ ; }, abstract = {The ability to detect and quantify microbiota over time from shotgun metagenomic data has a plethora of clinical, basic science and public health applications. Given these applications, and the observation that pathogens and other taxa of interest can reside at low relative abundance, there is a critical need for algorithms that accurately profile low-abundance microbial taxa with strain-level resolution. Here we present ChronoStrain: a sequence quality- and time-aware Bayesian model for profiling strains in longitudinal samples. ChronoStrain explicitly models the presence or absence of each strain and produces a probability distribution over abundance trajectories for each strain. Using synthetic and semi-synthetic data, we demonstrate how ChronoStrain outperforms existing methods in abundance estimation and presence/absence prediction. Applying ChronoStrain to two human microbiome datasets demonstrated its improved interpretability for profiling Escherichia coli strain blooms in longitudinal faecal samples from adult women with recurring urinary tract infections, and its improved accuracy for detecting Enterococcus faecalis strains in infant faecal samples. Compared with state-of-the-art methods, ChronoStrain's ability to detect low-abundance taxa is particularly stark.}, }
@article {pmid40322904, year = {2025}, author = {Hinkkanen, VI and Savinko, T and Palosuo, K and Alenius, H and Mäkelä, MJ and Karisola, P}, title = {Regular Allergen Exposure During Oral Immunotherapy Alters the Transcriptomic Innate Immune Response After Cellular Restimulation in Children With Egg Allergy.}, journal = {Journal of investigational allergology &amp; clinical immunology}, volume = {}, number = {}, pages = {0}, doi = {10.18176/jiaci.1079}, pmid = {40322904}, issn = {1018-9068}, abstract = {BACKGROUND AND OBJECTIVES: Oral immunotherapy (OIT) is a promising treatment for food allergies. However, the molecular mechanisms leading to desensitization remain unknown. To better understand the immunological mechanisms and transcriptional changes underlying desensitization to food allergens during OIT.<br><br>METHODS: Our cohort consisted of 40 Finnish children with egg allergy who underwent OIT. Peripheral blood mononuclear cells (PBMCs) were collected at 0, 3, and 8 months of therapy and stimulated with an egg allergen extract. Differentially expressed genes (DEGs) were identified based on quantile-normalized and batch-corrected microarray data using a linear model. Gene enrichment and Pearson correlation analyses were conducted.<br><br>RESULTS: After 8 months of therapy, 45% of patients were fully desensitized and 55% partially desensitized. Stimulation with egg yielded 49 DEGs at 0 months, 723 DEGs at 3 months, and 759 DEGs at 8 months in PBMCs after comparison with unstimulated controls. At 8 months of OIT, allergen stimulation led to down regulation of proinflammatory pathways, as well as IL-4 and IL-13 signaling. At baseline, the immune response in the fully desensitized group was more reactive than in the partially desensitized group.<br><br>CONCLUSIONS: During OIT, general immune activity is increased, especially the number of down-regulated genes, suggesting active immune suppression. Transcriptomic profiles differ between fully and partially desensitized patients, with a notably more reactive immune response in the fully desensitized group at baseline. Innate immunity seems to play a significant role in the development of desensitization during OIT.}, }
@article {pmid40322851, year = {2025}, author = {Zeng, Z and Li, M and Vannucci, M}, title = {Bayesian covariate-dependent graph learning with a dual group spike-and-slab prior.}, journal = {Biometrics}, volume = {81}, number = {2}, pages = {}, doi = {10.1093/biomtc/ujaf053}, pmid = {40322851}, issn = {1541-0420}, support = {2153704//DMS/NIGMS/ ; //National Science Foundation/ ; }, mesh = {Bayes Theorem ; Computer Simulation ; Humans ; *Models, Statistical ; Microbiota ; Algorithms ; }, abstract = {Covariate-dependent graph learning has gained increasing interest in the graphical modeling literature for the analysis of heterogeneous data. This task, however, poses challenges to modeling, computational efficiency, and interpretability. The parameter of interest can be naturally represented as a 3-dimensional array with elements that can be grouped according to 2 directions, corresponding to node level and covariate level, respectively. In this article, we propose a novel dual group spike-and-slab prior that enables multi-level selection at covariate-level and node-level, as well as individual (local) level sparsity. We introduce a nested strategy with specific choices to address distinct challenges posed by the various grouping directions. For posterior inference, we develop a full Gibbs sampler for all parameters, which mitigates the difficulties of parameter tuning often encountered in high-dimensional graphical models and facilitates routine implementation. Through simulation studies, we demonstrate that the proposed model outperforms existing methods in its accuracy of graph recovery. We show the practical utility of our model via an application to microbiome data where we seek to better understand the interactions among microbes as well as how these are affected by relevant covariates.}, }
@article {pmid40315414, year = {2025}, author = {Galperina, A and Lugli, GA and Milani, C and De Vos, WM and Ventura, M and Salonen, A and Hurwitz, B and Ponsero, AJ}, title = {The Aggregated Gut Viral Catalogue (AVrC): A unified resource for exploring the viral diversity of the human gut.}, journal = {PLoS computational biology}, volume = {21}, number = {5}, pages = {e1012268}, doi = {10.1371/journal.pcbi.1012268}, pmid = {40315414}, issn = {1553-7358}, abstract = {The growing interest in the role of the gut virome in human health and disease, has led to several recent large-scale viral catalogue projects mining human gut metagenomes each using varied computational tools and quality control criteria. Importantly, there has been to date no consistent comparison of these catalogues' quality, diversity, and overlap. In this project, we therefore systematically surveyed nine previously published human gut viral catalogues. While these catalogues collectively screened >40,000 human fecal metagenomes, 82% of the recovered 345,613 viral sequences were unique to one catalogue, highlighting limited redundancy between the ressources and suggesting the need for an aggregated resource bringing these viral sequences together. We further expanded these viral catalogues by mining 7,867 infant gut metagenomes from 12 large-scale infant studies collected in 9 different countries. From these datasets, we constructed the Aggregated Gut Viral Catalogue (AVrC), a unified modular resource containing 1,018,941 dereplicated viral sequences (449,859 species-level vOTUs). Using computational inference tools, annotations were obtained for each vOTU representative sequence quality, viral taxonomy, predicted viral lifestyle, and putative host. This project aims to facilitate the reuse of previously published viral catalogues by the research community and follows a modular framework to enable future expansions as novel data becomes available.}, }
@article {pmid40314735, year = {2025}, author = {Rohde, C}, title = {[Basic knowledge of phages and their therapeutic application].}, journal = {Bundesgesundheitsblatt, Gesundheitsforschung, Gesundheitsschutz}, volume = {}, number = {}, pages = {}, pmid = {40314735}, issn = {1437-1588}, abstract = {Phages (bacteriophages) are viruses that specifically infect and kill bacteria. They are very abundant in nature, playing a highly relevant role in microbial ecosystems. In medicine, they are investigated as a potential alternative or supplement to antibiotics and can be used to treat wound, urinary tract and lung infections, for example. Single phages or so-called "phage cocktails" are applied.This overview article on basic knowledge of phages sheds light on well-known keywords from classical knowledge of phage biology and on state-of-the-art research focuses. Mechanisms of phage activity are presented as a basis for therapeutic application. Particularly, the phage-host interaction, lysis mechanisms, phage morphologies and specific methods for visualisation are discussed. Being part of the human microbiome, phages contribute to immune defence, especially in the mucosa. Temperate phages that are able to reside in bacterial genomes as prophages and therefore not suitable for therapy use as well as the CrAss phages (Crassvirales) and Lak megaphages discovered in recent years are also introduced. Further topics are bacterial phage defence, phage resistance and phage-antibiotic synergies. An outlook on future research is given, emphasising the importance of a coordinated collection of scientific results.Phages should not replace antibiotics, but they can even improve their efficiency. Currently, the licensing processes for phage therapy are still challenging. However, trust in phage preparations must be based on quality, which has to be guaranteed by harmonised standards.}, }
@article {pmid40314614, year = {2025}, author = {Lee, WM and Ahn, SY and Lee, GS and Park, I and Kim, J and Lee, SH and Lee, S and Kim, CS}, title = {Discovery and Biosynthesis of Indole-Functionalized Metabolites from the Human Blood Bacterium, Paracoccus sanguinis, and Their Anti-Skin Aging Activity.}, journal = {Journal of natural products}, volume = {}, number = {}, pages = {}, doi = {10.1021/acs.jnatprod.4c01354}, pmid = {40314614}, issn = {1520-6025}, abstract = {The human microbiome plays a crucial role in health and disease, with microbial metabolites acting as key mediators of physiological processes. While extensive research has focused on gut-derived microbes, the metabolic contributions of blood-derived bacteria remain underexplored. Here, we investigate the facultative anaerobe Paracoccus sanguinis, a Gram-negative bacterium isolated from human blood, and its metabolome, revealing insights into its potential impacts on health and disease. Using advanced analytical methods, we characterized 12 metabolites (1-12), including six novel compounds (1-3, 9, 10, and 12). Biosynthetic studies demonstrated that these metabolites are derived through enzymatic and nonenzymatic pathways. Functional evaluations revealed significant antiaging activities for 1, 6, and 11 in TNF-α-stimulated normal human dermal fibroblasts (NHDFs), including suppression of reactive oxygen species (ROS), inhibition of matrix metalloproteinase-1 (MMP-1) secretion, and reduction of inflammatory cytokines interleukin (IL)-6 and IL-8. Among the tested compounds, 11 exhibited the highest antiaging efficacy, highlighting its potential as a candidate for therapeutic applications targeting skin aging. This study elucidates the biosynthetic pathways of P. sanguinis metabolites and their antiskin aging activity, underscoring their potential in modulating skin health and offering novel insights into the functional roles of blood-derived microbiota in human health.}, }
@article {pmid40311618, year = {2025}, author = {Andreu-Sánchez, S and Blanco-Míguez, A and Wang, D and Golzato, D and Manghi, P and Heidrich, V and Fackelmann, G and Zhernakova, DV and Kurilshikov, A and Valles-Colomer, M and Weersma, RK and Zhernakova, A and Fu, J and Segata, N}, title = {Global genetic structure of human gut microbiome species is related to geographic location and host health.}, journal = {Cell}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.cell.2025.04.014}, pmid = {40311618}, issn = {1097-4172}, abstract = {The human gut harbors thousands of microbial species, each exhibiting significant inter-individual genetic variability. Although many studies have associated microbial relative abundances with human-health-related phenotypes, the substantial intraspecies genetic variability of gut microbes has not yet been comprehensively considered, limiting the potential of linking such genetic traits with host conditions. Here, we analyzed 32,152 metagenomes from 94 microbiome studies across the globe to investigate the human microbiome intraspecies genetic diversity. We reconstructed 583 species-specific phylogenies and linked them to geographic information and species' horizontal transmissibility. We identified 484 microbial-strain-level associations with 241 host phenotypes, encompassing human anthropometric factors, biochemical measurements, diseases, and lifestyle. We observed a higher prevalence of a Ruminococcus gnavus clade in nonagenarians correlated with distinct plasma bile acid profiles and a melanoma and prostate-cancer-associated Collinsella clade. Our large-scale intraspecies genetic analysis highlights the relevance of strain diversity as it relates to human health.}, }
@article {pmid40304519, year = {2025}, author = {Swayambhu, M and Gysi, M and Haas, C and Schuh, L and Walser, L and Javanmard, F and Flury, T and Ahannach, S and Lebeer, S and Hanssen, E and Snipen, L and Bokulich, NA and Kümmerli, R and Arora, N}, title = {Standardizing a microbiome pipeline for body fluid identification from complex crime scene stains.}, journal = {Applied and environmental microbiology}, volume = {}, number = {}, pages = {e0187124}, doi = {10.1128/aem.01871-24}, pmid = {40304519}, issn = {1098-5336}, abstract = {Recent advances in next-generation sequencing have opened up new possibilities for applying the human microbiome in various fields, including forensics. Researchers have capitalized on the site-specific microbial communities found in different parts of the body to identify body fluids from biological evidence. Despite promising results, microbiome-based methods have not been integrated into forensic practice due to the lack of standardized protocols and systematic testing of methods on forensically relevant samples. Our study addresses critical decisions in establishing these protocols, focusing on bioinformatics choices and the use of machine learning to present microbiome results in case reports for forensically relevant and challenging samples. In our study, we propose using operational taxonomic units (OTUs) for read data processing and generating heterogeneous training data sets for training a random forest classifier. We incorporated six forensically relevant classes: saliva, semen, skin from hand, penile skin, urine, and vaginal/menstrual fluid, and our classifier achieved a high weighted average F1 score of 0.89. Systematic testing on mock forensic samples, including mixed-source samples and underwear, revealed reliable detection of at least one component of the mixture and the identification of vaginal fluid from underwear substrates. Additionally, when investigating the sexually shared microbiome (sexome) of heterosexual couples, our classifier could potentially infer the nature of sexual activity. We therefore highlight the value of the sexome for assessing the nature of sexual activities in forensic investigations while delineating areas that warrant further research.IMPORTANCEMicrobiome-based analyses combined with machine learning offer potential avenues for use in forensic science and other applied fields, yet standardized protocols remain lacking. Moreover, machine learning classifiers have shown promise for predicting body sites in forensics, but they have not been systematically evaluated on complex mixed-source samples. Our study addresses key decisions for establishing standardized protocols and, to our knowledge, is the first to report classification results from uncontrolled mixed-source samples, including sexome (sexually shared microbiome) samples. In our study, we explore both the strengths and limitations of classifying the mixed-source samples while also providing options for tackling the limitations.}, }
@article {pmid40302548, year = {2025}, author = {Singh, A and Mazumder, A and Das, S and Kanda, A and Tyagi, PK and Chaitanya, MVNL}, title = {Harnessing the Power of Probiotics: Boosting Immunity and Safeguarding against Various Diseases and Infections.}, journal = {Recent advances in anti-infective drug discovery}, volume = {20}, number = {1}, pages = {5-29}, pmid = {40302548}, issn = {2772-4352}, mesh = {*Probiotics/administration &amp; dosage/therapeutic use ; Humans ; Animals ; Gastrointestinal Microbiome/immunology ; *Virus Diseases/immunology/prevention &amp; control ; }, abstract = {The human microbiome, a diverse microorganism community, crucially defends against pathogens. Probiotics, postbiotics, and paraprobiotics alone and in combination are potent in countering fungal and waterborne infections, particularly against viral threats. This review focuses on the mechanisms of the microbiome against viral infections, emphasizing probiotic interventions. Certain Lactic Acid Bacteria (LAB) strains effectively eliminate toxic aflatoxin B1 (AFB1) from microfungi-produced mycotoxins. LAB binding to AFB1 persists post-gastric digestion, and pre-incubation with mycotoxins reduces probiotic adhesion to mucus. Oral probiotic administration in animals increases mycotoxin excretion, reducing associated health risks. Bifidobacterium longum and Lactobacillus rhamnosus show exceptional efficacy in removing cyanobacterial toxin microcystin-LR from drinking water. Engineered probiotics promise advanced therapeutic applications for metabolic disorders, Alzheimer's, and type 1 diabetes, serving as diagnostic tools for detecting pathogens and inflammation markers. In antimicrobial peptide production, genetically modified probiotics producing human β-defensin 2 (HBD2) treat Crohn's disease with implemented biocontainment strategies preventing unintended environmental impacts.}, }
@article {pmid40301726, year = {2025}, author = {Yao, C and Zhang, Y and You, L and E, J and Wang, J}, title = {Comparative analysis of three experimental methods for revealing human fecal microbial diversity.}, journal = {BMC microbiology}, volume = {25}, number = {1}, pages = {258}, pmid = {40301726}, issn = {1471-2180}, support = {2024L154//the Fundamental Research Program of Shanxi Province/ ; 202403021212101//the Science and Technology Innovation Project of Shanxi Provincial Universities/ ; 2018ZD14//the Major Program of Natural Science Foundation of Inner Mongolia/ ; }, abstract = {Due to the heterogeneity of the human gut environment, the gut microbiota is complex and diverse, and has been insufficiently explored. In this study, one fresh fecal sample was cultured using 12 commercial or modified media and incubation of culture plates anaerobically and aerobically, the conventional experienced colony picking (ECP) was first used to isolate the colonies and obtain pure culture strains. On this basis, all the colonies grown on the culture plates were collected for culture-enriched metagenomic sequencing (CEMS), and the original sample was also subjected to direct culture-independent metagenomic sequencing (CIMS), the study compared the effects of three methods for analyzing the microbiota contained in the sample. It was found that compared with CEMS, conventional ECP failed to detect a large proportion of strains grown in culture media, resulting in missed detection of culturable microorganisms in the gut. Microbes identified by CEMS and CIMS showed a low degree of overlap (18% of species), whereas species identified by CEMS and CIMS alone accounted for 36.5% and 45.5%, respectively. It suggests that both culture-dependent and culture-independent approaches are essential in revealing gut microbial diversity. Moreover, based on the CEMS results, growth rate index (GRiD) values for various strains on different media were calculated to predict the optimal medium for bacterial growth; this method can be used to design new media for intestinal microbial isolation, promote the recovery of specific microbiota, and obtain new insights into the human microbiome diversity. This is among the first studies on CEMS of the human gut microbiota.}, }
@article {pmid40299456, year = {2025}, author = {Meiirmanova, Z and Mukhanbetzhanov, N and Jarmukhanov, Z and Vinogradova, E and Kozhakhmetova, S and Morenko, M and Duisebayeva, A and Poddighe, D and Kushugulova, A and Kozhakhmetov, S}, title = {Alterations in Gut Microbiota of Infants Born to Mothers with Obesity.}, journal = {Biomedicines}, volume = {13}, number = {4}, pages = {}, doi = {10.3390/biomedicines13040838}, pmid = {40299456}, issn = {2227-9059}, support = {Grant No. AP19575153 "Metagenomic predictors of childhood obesity, cross-talk with maternal mi-croflora", Grant No. AP23489538 and Grant No. BR21882152//Science Committee of the Ministry of Science and Higher Education of the Republic of Kazakhstan/ ; Grant No. 20122022CRP1602//Nazarbayev University under Collaborative Research Program/ ; }, abstract = {Background: The impact of maternal obesity on offspring health remains a major and pressing issue. We investigated its impact on the development of the infant gut microbiome during the first six months of life, examining the taxonomic composition, metabolic pathways, and antibiotic resistance genes. Methods: Twenty-four mother-infant pairs were divided into maternally obese (OB, BMI > 36) and normal weight (BM) groups. Shotgun metagenomic sequencing was performed on stool samples collected at birth and at 1, 3, and 6 months. A total of 12 maternal samples and 23 infant samples (n = 35) in the obese group and 12 maternal samples and 30 infant samples (n = 42) in the control group were sequenced. The analysis included taxonomic profiling (MetaPhlAn 4), metabolic pathway analysis (HUMAnN 3), and antibiotic resistance gene screening (CARD/ABRicate). Results: The OB group showed reduced alpha diversity in the first month (p ≤ 0.01) and an increased Firmicutes/Bacteroidetes ratio, peaking at 3 months (p ≤ 0.001). The metabolic profiling revealed enhanced carbohydrate breakdown (p ≤ 0.001) in the BM group and lipid biosynthesis (p ≤ 0.0001) in the OB group pathways. Strong correlations emerged between Lactobacillales and fatty acid biosynthesis (r = 0.7, p ≤ 0.0001) and between Firmicutes and lincosamide (r = 0.8, p ≤ 0.0001). Conclusions: The infants of obese mothers had significantly altered development of the infant gut microbiome, affecting both composition and metabolic potential. These changes may have long-term health consequences and suggest potential therapeutic targets for intervention.}, }
@article {pmid40298367, year = {2025}, author = {Zhou, Z and Ma, Y and Zhang, D and Ji, R and Wang, Y and Zhao, J and Ma, C and Zhu, H and Shen, H and Jiang, X and Niu, Y and Lu, J and Zhang, B and Tu, L and Zhang, H and Ma, X and Chen, P}, title = {Microbiome and fragmentation pattern of blood cell-free DNA and fecal metagenome enhance colorectal cancer micro-dysbiosis and diagnosis analysis: a proof-of-concept study.}, journal = {mSystems}, volume = {}, number = {}, pages = {e0027625}, doi = {10.1128/msystems.00276-25}, pmid = {40298367}, issn = {2379-5077}, abstract = {Colorectal cancer (CRC) is the third most common cancer, and it can be prevented by performing early screening. As a hallmark of cancer, the human microbiome plays important roles in the occurrence and development of CRC. Recently, the blood microbiome has been proposed as an effective diagnostic tool for various diseases, yet its performance on CRC deserves further exploration. In this study, 133 human feces and 120 blood samples are collected, including healthy individuals, adenoma patients, and CRC patients. The blood cfDNA and fecal genome are subjected to shotgun metagenome sequencing. After removing human sequences, the microbial sequences in blood are analyzed. Based on the differential microbes and functions, random forest (RF) models are constructed for adenoma and CRC diagnosis. The results show that alterations of blood microbial signatures can be captured under low coverage (even at 3×). RF diagnostic models based on blood microbial markers achieve high area under the curve (AUC) values for adenoma patients (0.8849) and CRC patients (0.9824). When the fragmentation pattern is combined with microbial and KEGG markers, higher AUC values are obtained. Furthermore, compared to the blood microbiome, the fecal microbiome shows a different community composition, whereas their changes in KEGG pathways are similar. Pathogenic bacteria Fusobacterium nucleatum (F. nucleatum) in feces increased gradually from the healthy group to the adenoma and CRC groups. Additionally, F. nucleatum in feces and blood shows a positive correlation in CRC patients. Cumulatively, the integration of blood microbiome and fragmentation pattern is promising for CRC diagnosis.IMPORTANCEThe cell-free DNA of the human microbiome can enter the blood and can be used for cancer diagnosis, whereas its diagnostic potential in colorectal cancer and association with gut microbiome has not been explored. The microbial sequences in blood account for less than 1% of the total sequences. The blood microbial composition, KEGG functions, and fragmentation pattern are different among healthy individuals, adenoma patients, and CRC patients. Machine learning models based on these differential characteristics achieve high diagnostic accuracy, especially when they are integrated with fragmentation patterns. The great difference between fecal and blood microbiomes indicates that microbial sequences in blood may originate from various organs. Therefore, this study provides new insights into the community composition and functions of the blood microbiome of CRC and proposes an effective non-invasive diagnostic tool.}, }
@article {pmid40297591, year = {2025}, author = {Pei, X and Liu, L and Han, Y}, title = {Advances in human microbiome and prostate cancer research.}, journal = {Frontiers in immunology}, volume = {16}, number = {}, pages = {1576679}, pmid = {40297591}, issn = {1664-3224}, mesh = {Humans ; *Prostatic Neoplasms/microbiology/therapy/immunology/metabolism/etiology ; Male ; *Microbiota ; *Gastrointestinal Microbiome ; Tumor Microenvironment/immunology ; Animals ; }, abstract = {Prostate cancer (PCa) is the second most common malignant tumor in men worldwide, and its metastatic and heterogeneous nature makes it significantly more difficult to treat. Recent studies have revealed the critical role of microbiota in PCa occurrence, progression, and treatment. Accumulating evidence from 16S rRNA and metagenomic sequencing suggests the presence of specific microbiota in prostate tissues and macrogenomics techniques: cancerous tissues are enriched with pro-inflammatory genera (e.g., Fusobacterium, Propionibacterium acnes), whereas commensal bacteria (e.g., Pseudomonas) are more common in paracancerous tissues. The microbiota drive tumor progression through activation of the NF-κB/STAT3 pathway to induce chronic inflammation, modulation of the immune microenvironment (e.g., Treg/Th17 imbalance and M2-type macrophage polarization), and metabolite (e.g., LPS, short-chain fatty acids)-mediated hormonal and epigenetic regulation. In terms of clinical translation, urinary microbiota characterization combined with metabolomics analysis may enhance diagnostic specificity, while gut flora modulation (e.g., probiotic interventions or fecal transplants) may improve resistance to androgen deprivation therapy. Current challenges include sequencing accuracy of low-biomass samples, limitations of causal mechanism validation models, and large cohort heterogeneity. In the future, it will be necessary to integrate multi-omics technologies to explore the bidirectional regulation of the "gut-prostate axis" and develop personalized therapeutic strategies targeting microorganisms. In this paper, we systematically review the interactions between microbiota and PCa and their clinical potentials to provide a theoretical basis for precision diagnosis and treatment.}, }
@article {pmid40296251, year = {2025}, author = {Zheng, H and Chen, Y and Lu, S and Liu, Z and Ma, Y and Zhang, C and Zhang, Y and Zhang, J and Liu, C and Chu, M and Pei, F and Liu, S and Duan, L}, title = {Mechanosensory Piezo2 regulated by gut microbiota participates in the development of visceral hypersensitivity and intestinal dysmotility.}, journal = {Gut microbes}, volume = {17}, number = {1}, pages = {2497399}, doi = {10.1080/19490976.2025.2497399}, pmid = {40296251}, issn = {1949-0984}, mesh = {*Gastrointestinal Microbiome/physiology ; Animals ; Humans ; Mice ; *Irritable Bowel Syndrome/microbiology/physiopathology/metabolism/therapy ; *Ion Channels/metabolism/genetics ; Male ; Female ; Fecal Microbiota Transplantation ; *Gastrointestinal Motility ; Adult ; Middle Aged ; Colon/metabolism ; Mice, Inbred C57BL ; Feces/microbiology ; Fusobacterium/physiology ; Dysbiosis/microbiology ; Disease Models, Animal ; Ganglia, Spinal/metabolism ; Akkermansia ; }, abstract = {The gut microbiota plays a crucial role in the manifestation of intestinal dysfunction associated with irritable bowel syndrome (IBS). The mechanosensory Piezo2 has been implicated in the regulation of intestinal function. However, it remains unclear whether Piezo2 is modulated by the gut microbiota, thus contributing to the development of visceral hypersensitivity and gut dysmotility. The study enrolled patients with diarrhea-predominant IBS (IBS-D) alongside healthy controls (HC). Questionnaires, rectal barostat test, and colonoscopy with mucosal biopsy were conducted. Fecal microbiota transplantation (FMT) was performed using samples from HC or IBS-D patients, and interventions with Akkermansia muciniphila or Fusobacterium varium were carried out on colon- or dorsal root ganglion (DRG)- Piezo2 knockdown pseudo-germ-free mice. Visceral sensitivity and intestinal motility were assessed. Piezo2 levels were detected using western blot and immunofluorescence. Fecal 16S rRNA sequencing and cecum untargeted metabolomics analysis, followed by molecular docking predictions of Piezo2, were also performed. The ratio of Piezo2[+]/5-HT[+] cells was lower in IBS-D patients, positively correlated with visceral sensation and intestinal dysbiosis. The mice that received FMT from IBS-D patients exhibited colonic dysmotility and visceral hypersensitivity, along with elevated Piezo2 protein levels in the colon and DRG. Knockdown of Piezo2 in the colon or DRG ameliorated the FMT-induced colonic dysmotility and visceral hypersensitivity. Fecal 16S rRNA sequencing revealed distinct microbiota composition. Notably, Fusobacterium varium, but not Akkermansia muciniphila, induced gut dysmotility and visceral hypersensitivity, effects that could be alleviated by colon or DRG Piezo2 knockdown. Additionally, Fusobacterium varium lead to increased Piezo2 protein levels, as well as elevated levels of indole-3-acetic acid and indole-3-acrylic acid, which were predicted to bind to Piezo2, causing disturbances. Piezo2 can be regulated by gut microbiota and involved in visceral hypersensitivity and colonic dysmotility, with Fusobacterium varium playing a crucial role.}, }
@article {pmid40296128, year = {2025}, author = {Adlakha, YK and Chhabra, R}, title = {The human microbiome: redefining cancer pathogenesis and therapy.}, journal = {Cancer cell international}, volume = {25}, number = {1}, pages = {165}, pmid = {40296128}, issn = {1475-2867}, abstract = {The human microbiome has always been an important determinant of health and recently, its role has also been described in cancer. The altered microbiome could aid cancer progression, modulate chemoresistance and significantly alter drug efficacy. The broad implications of microbes in cancer have prompted researchers to investigate the microbe-cancer axis and identify whether modifying the microbiome could sensitize cancer cells for therapy and improve the survival outcome of cancer patients. The preclinical data has shown that enhancing the number of specific microbial species could restore the patients' response to cancer drugs and the microbial biomarkers may play a vital role in cancer diagnostics. The elucidation of detailed interactions of the human microbiota with cancer would not only help identify the novel drug targets but would also enhance the efficacy of existing drugs. The field exploring the emerging roles of microbiome in cancer is at a nascent stage and an in-depth scientific perspective on this topic would make it more accessible to a wider audience. In this review, we discuss the scientific evidence connecting the human microbiome to the origin and progression of cancer. We also discuss the potential mechanisms by which microbiota affects initiation of cancer, metastasis and chemoresistance. We highlight the significance of the microbiome in therapeutic outcome and evaluate the potential of microbe-based cancer therapy.}, }
@article {pmid40291991, year = {2025}, author = {Crakes, KR and Questell, L and Soni, S and Suez, J}, title = {Impacts of non-nutritive sweeteners on the human microbiome.}, journal = {Immunometabolism (Cobham, Surrey)}, volume = {7}, number = {2}, pages = {e00060}, pmid = {40291991}, issn = {2633-0407}, abstract = {Replacing sugar with non-nutritive sweeteners (NNS) is a common dietary strategy for reducing the caloric content and glycemic index of foods and beverages. However, the efficacy of this strategy in preventing and managing metabolic syndrome and its associated comorbidities remains uncertain. Human cohort studies suggest that NNS contribute to, rather than prevent, metabolic syndrome, whereas randomized controlled trials yield heterogeneous outcomes, ranging from beneficial to detrimental impacts on cardiometabolic health. The World Health Organization recently issued a conditional recommendation against using NNS, citing the need for additional evidence causally linking sweeteners to health effects. One proposed mechanism through which NNS induce metabolic derangements is through disruption of the gut microbiome, a link strongly supported by evidence in preclinical models. This review summarizes the evidence for similar effects in interventional and observational trials in humans. The limited available data highlight heterogeneity between trials, as some, but not all, find NNS consumption associated with microbiome modulation as well as metabolic effects independent of sweetener type. In other trials, the lack of microbiome changes coincides with the absence of metabolic effects. We discuss the hypothesis that the impacts of NNS on health are personalized and microbiome dependent. Thus, a precision nutrition approach may help resolve the conflicting reports regarding NNS impacts on the microbiome and health. This review also discusses additional factors contributing to study heterogeneity that should be addressed in future clinical trials to clarify the relationship between NNS, the microbiome, and health to better inform dietary guidelines and public health policies.}, }
@article {pmid40264322, year = {2025}, author = {Jain, MS and Prasanthi, S and Bommala, ND and Goudanavar, P and Naveen, NR}, title = {Harnessing the Human Microbiome for Innovative Drug Delivery Systems: Exploring Pharmacomicrobiomics and Targeted Therapies.}, journal = {Current pharmaceutical design}, volume = {}, number = {}, pages = {}, doi = {10.2174/0113816128354250250326045943}, pmid = {40264322}, issn = {1873-4286}, abstract = {The human gut microbiome has emerged as a crucial component of health and disease, presenting novel opportunities for the development of drug delivery systems based on microbiome interactions. This paper explores advanced strategies utilizing microorganisms, engineered bacteria, viruses, and bacteria-encapsulated nanoparticles as next-generation therapeutic vehicles. Focusing on analytical approaches to phage therapy and bio-hybrid bacteria for targeted drug delivery, the article highlights recent breakthroughs in colon-specific targeting for gastrointestinal disorders. The study also delves into the emerging field of pharmacomicrobiomics, with an emphasis on applications in cancer, cardiovascular, digestive, and nervous system treatments, specifically targeting key drug classes such as ACE inhibitors, proton-pump inhibitors, and NSAIDs. Challenges related to cytotoxicity and toxicity are addressed, offering proposals for safer therapeutic applications. This review underscores the transformative potential of the microbiome in personalized medicine and targeted drug delivery, with a focus on its integration with advanced technologies to optimize therapeutic outcomes.}, }
@article {pmid40261032, year = {2025}, author = {Cho, M-Y and Eom, J-H and Choi, E-M and Yang, S-J and Lee, D and Kim, YY and Kim, H-S and Hwang, I}, title = {Recent advances in therapeutic probiotics: insights from human trials.}, journal = {Clinical microbiology reviews}, volume = {}, number = {}, pages = {e0024024}, doi = {10.1128/cmr.00240-24}, pmid = {40261032}, issn = {1098-6618}, abstract = {SUMMARYRecent advances in therapeutic probiotics have shown promising results across various health conditions, reflecting a growing understanding of the human microbiome's role in health and disease. However, comprehensive reviews integrating the diverse therapeutic effects of probiotics in human subjects have been limited. By analyzing randomized controlled trials (RCTs) and meta-analyses, this review provides a comprehensive overview of key developments in probiotic interventions targeting gut, liver, skin, vaginal, mental, and oral health. Emerging evidence supports the efficacy of specific probiotic strains and combinations in treating a wide range of disorders, from gastrointestinal (GI) and liver diseases to dermatological conditions, bacterial vaginosis, mental disorders, and oral diseases. We discuss the expanding understanding of microbiome-organ connections underlying probiotic mechanisms of action. While many clinical trials demonstrate significant benefits, we acknowledge areas requiring further large-scale studies to establish definitive efficacy and optimal treatment protocols. The review addresses challenges in standardizing probiotic research methodologies and emphasizes the importance of considering individual variations in microbiome composition and host genetics. Additionally, we explore emerging concepts such as the oral-gut-brain axis and future directions, including high-resolution microbiome profiling, host-microbe interaction studies, organoid models, and artificial intelligence applications in probiotic research. Overall, this review offers a comprehensive update on the current state of therapeutic probiotics across multiple domains of human health, providing insights into future directions and the potential for probiotics to revolutionize preventive and therapeutic medicine.}, }
@article {pmid40257583, year = {2025}, author = {Hu, J and Chen, W and Zhu, R and Yang, F and Xu, J and Xiang, B and Li, Y and Wang, W and Zhu, L and Chen, G and Zhi, M}, title = {Correction: Dietary risk factors in Crohn's disease and ulcerative colitis: a cohort study with paired healthy relatives as controls.}, journal = {European journal of nutrition}, volume = {64}, number = {4}, pages = {161}, doi = {10.1007/s00394-025-03669-y}, pmid = {40257583}, issn = {1436-6215}, }
@article {pmid40253432, year = {2025}, author = {Kelliher, JM and Aljumaah, M and Bordenstein, SR and Brister, JR and Chain, PSG and Dundore-Arias, JP and Emerson, JB and Fernandes, VMC and Flores, R and Gonzalez, A and Hansen, ZA and Hatcher, EL and Jackson, SA and Kellogg, CA and Madupu, R and Miller, CML and Mirzayi, C and Moustafa, AM and Mungall, C and Oliver, A and Pariente, N and Pett-Ridge, J and Record, S and Reji, L and Reysenbach, AL and Rich, VI and Richardson, L and Schriml, LM and Shabman, RS and Sierra, MA and Sullivan, MB and Sundaramurthy, P and Thibault, KM and Thompson, LR and Tighe, S and Vereen, E and Eloe-Fadrosh, EA}, title = {Microbiome data management in action workshop: Atlanta, GA, USA, June 12-13, 2024.}, journal = {Environmental microbiome}, volume = {20}, number = {1}, pages = {40}, pmid = {40253432}, issn = {2524-6372}, support = {2422717//Directorate for Biological Sciences/ ; 2422717//Directorate for Biological Sciences/ ; 2422717//Directorate for Biological Sciences/ ; 2422717//Directorate for Biological Sciences/ ; 2422717//Directorate for Biological Sciences/ ; 2422717//Directorate for Biological Sciences/ ; 2422717//Directorate for Biological Sciences/ ; 2422717//Directorate for Biological Sciences/ ; 2422717//Directorate for Biological Sciences/ ; 2422717//Directorate for Biological Sciences/ ; 2422717//Directorate for Biological Sciences/ ; 2422717//Directorate for Biological Sciences/ ; 2422717//Directorate for Biological Sciences/ ; 2422717//Directorate for Biological Sciences/ ; 2422717//Directorate for Biological Sciences/ ; 2422717//Directorate for Biological Sciences/ ; 2422717//Directorate for Biological Sciences/ ; 2422717//Directorate for Biological Sciences/ ; 2422717//Directorate for Biological Sciences/ ; 2422717//Directorate for Biological Sciences/ ; 2422717//Directorate for Biological Sciences/ ; 2422717//Directorate for Biological Sciences/ ; 2422717//Directorate for Biological Sciences/ ; 2422717//Directorate for Biological Sciences/ ; 2422717//Directorate for Biological Sciences/ ; 2422717//Directorate for Biological Sciences/ ; 2422717//Directorate for Biological Sciences/ ; 2422717//Directorate for Biological Sciences/ ; 2422717//Directorate for Biological Sciences/ ; 2422717//Directorate for Biological Sciences/ ; 2422717//Directorate for Biological Sciences/ ; 2422717//Directorate for Biological Sciences/ ; 2422717//Directorate for Biological Sciences/ ; 2422717//Directorate for Biological Sciences/ ; 2422717//Directorate for Biological Sciences/ ; 2422717//Directorate for Biological Sciences/ ; 2422717//Directorate for Biological Sciences/ ; }, abstract = {Microbiome research is revolutionizing human and environmental health, but the value and reuse of microbiome data are significantly hampered by the limited development and adoption of data standards. While several ongoing efforts are aimed at improving microbiome data management, significant gaps still remain in terms of defining and promoting adoption of consensus standards for these datasets. The Strengthening the Organization and Reporting of Microbiome Studies (STORMS) guidelines for human microbiome research have been endorsed and successfully utilized by many research organizations, publishers, and funding agencies, and have been recognized as a consensus community standard. No equivalent effort has occurred for environmental, synthetic, and non-human host-associated microbiomes. To address this growing need within the microbiome research community, we convened the Microbiome Data Management in Action Workshop (June 12-13, 2024, in Atlanta, GA, USA), to bring together key decision makers in microbiome science including researchers, publishers, funders, and data repositories. The 50 attendees, representing the diverse and interdisciplinary nature of microbiome research, discussed recent progress and challenges, and brainstormed actionable recommendations and paths forward for coordinated environmental microbiome data management and the modifications necessary for the STORMS guidelines to be applied to environmental, non-human host, and synthetic microbiomes. The outcomes of this workshop will form the basis of a formalized data management roadmap to be implemented across the field. These best practices will drive scientific innovation now and in years to come as these data continue to be used not only in targeted reanalyses but in large-scale models and machine learning efforts.}, }
@article {pmid40251928, year = {2025}, author = {Boem, F and Lamminpää, I and Amedei, A}, title = {Updating the Discontinuity Theory to the Extended Immunity: The Symmunobiome Concept.}, journal = {European journal of immunology}, volume = {55}, number = {4}, pages = {e202451528}, doi = {10.1002/eji.202451528}, pmid = {40251928}, issn = {1521-4141}, support = {PE0000006//Italian Ministry of University and Research MNESYS/ ; B55F2100//University of Florence-European Union-Next Generation EU-CUP/ ; B83C22003920001//The National Recovery and Resilience Plan, Investment 1.5 Ecosystems of Innovation, Project Tuscany Health Ecosystem (THE), CUP/ ; }, mesh = {Humans ; *Microbiota/immunology ; Animals ; *Immune System/immunology ; Symbiosis/immunology ; Homeostasis/immunology ; *Immunity ; Biological Evolution ; Immunity, Innate ; Adaptive Immunity ; }, abstract = {The immune system (IS) is commonly understood as a system composed of specific cells and tissues that have evolved to contrast pathogens and defend the host. By virtue of this capacity, it has come to be considered capable of making an essential distinction, that between self versus non-self, which would contribute to a clear identity of the organism. However, in the wake of evolution and ecology, growing evidence suggests that the so-called immune system, which also evolved from symbiotic interactions with external agents, is not just a defensive system that merely protects the organism but, on the contrary, is involved in many global regulatory and homeostatic functions. Moreover, in performing these many functions, IS is not only an ensemble of host cells and tissues but functionally is constitutively determined by the interaction with a set of associated microorganisms, that is, the human microbiome. In this scenario, it is open-and-shut that the microbiome itself is a functional part of this extended immune system. Organisms and microbiomes together, therefore, form a functional whole, which constitutes a privileged form of biological organization. In light of this evidence showing the inadequacy of traditional accounts, we propose to extend and supplement the current IS conceptualization by introducing the notion of the symmunobiome. With this term, we intend to characterize the microbiome's own and unavoidable component to overall immune functionality. Therefore, we suggest a new immune system determination, articulated in three linked pillars-adaptive immunity, innate immunity, and symmunobiome-to better grasp the diverse functionality of extended immunity.}, }
@article {pmid40246834, year = {2025}, author = {Beaudoin, CA and Norget, S and Omran, Z and Hala, S and Daqeeq, AH and Burnet, PWJ and Blundell, TL and van Tonder, AJ}, title = {Similarity of drug targets to human microbiome metaproteome promotes pharmacological promiscuity.}, journal = {The pharmacogenomics journal}, volume = {25}, number = {3}, pages = {9}, pmid = {40246834}, issn = {1473-1150}, support = {ANTSRG 01/2019//Antibiotic Research UK (ANTRUK)/ ; }, mesh = {Humans ; Female ; *Microbiota/drug effects/genetics ; *Proteome/genetics ; *Gastrointestinal Microbiome/drug effects ; Vagina/microbiology ; Proteomics/methods ; Mouth/microbiology ; Bacteria/drug effects/genetics/metabolism ; }, abstract = {Similarity between candidate drug targets and human proteins is commonly assessed to minimize the occurrence of side effects. Although numerous drugs have been found to disrupt the health of the human microbiome, no comprehensive comparison between established drug targets and the human microbiome metaproteome has yet been conducted. Therefore, herein, sequence and structure alignments between human and pathogen drug targets and representative human gut, oral, and vaginal microbiome metaproteomes were performed. Both human and pathogen drug targets were found to be similar in sequence, function, structure, and drug binding capacity to proteins in diverse pathogenic and non-pathogenic bacteria from all three microbiomes. The gut metaproteome was identified as particularly susceptible overall to off-target effects. Certain symptoms, such as infections and immune disorders, may be more common among drugs that non-selectively target host microbiota. These findings suggest that similarities between human microbiome metaproteomes and drug target candidates should be routinely checked.}, }
@article {pmid40243330, year = {2025}, author = {Walker, AR and Pham, DN and Noeparvar, P and Peterson, AM and Lipp, MK and Lemos, JA and Zeng, L}, title = {Fructose activates a stress response shared by methylglyoxal and hydrogen peroxide in Streptococcus mutans.}, journal = {mBio}, volume = {}, number = {}, pages = {e0048525}, doi = {10.1128/mbio.00485-25}, pmid = {40243330}, issn = {2150-7511}, abstract = {Fructose catabolism by Streptococcus mutans is initiated by three phosphotransferase (PTS) transporters yielding fructose-1-phosphate (F-1-P) or fructose-6-phosphate. Deletion of one such F-1-P-generating PTS, fruI, was shown to reduce the cariogenicity of S. mutans in rats fed a high-sucrose diet. Moreover, a recent study linked fructose metabolism in S. mutans to a reactive electrophile species methylglyoxal. Here, we conducted a comparative transcriptomic analysis of S. mutans treated briefly with 50 mM fructose, 50 mM glucose, 5 mM methylglyoxal, or 0.5 mM hydrogen peroxide (H2O2). The results revealed a striking overlap between the fructose and methylglyoxal transcriptomes, totaling 176 genes, 61 of which were also shared with the H2O2 transcriptome. This core of 61 genes encompassed many of the same pathways affected by exposure to low pH or zinc intoxication. Consistent with these findings, fructose negatively impacted the metal homeostasis of a mutant deficient in zinc expulsion and the growth of a mutant of the major oxidative stress regulator SpxA1. Importantly, fructose metabolism lowered culture pH at a faster pace, allowed better survival under acidic and nutrient-depleted conditions, and enhanced the competitiveness of S. mutans against Streptococcus sanguinis, although a moderated level of F-1-P might further boost some of these benefits. Conversely, several commensal streptococcal species displayed a greater sensitivity to fructose that may negatively affect their persistence and competitiveness in dental biofilm. In conclusion, fructose metabolism is integrated into the stress core of S. mutans and regulates critical functions required for survival and its ability to induce dysbiosis in the oral cavity.IMPORTANCEFructose is a common monosaccharide in the biosphere, yet its overconsumption has been linked to various health problems in humans including insulin resistance, obesity, diabetes, non-alcoholic liver diseases, and even cancer. These effects are in large part attributable to the unique biochemical characteristics and metabolic responses associated with the degradation of fructose. Yet, an understanding of the effects of fructose on the physiology of bacteria and its implications for the human microbiome is severely lacking. Here, we performed a series of analyses on the gene regulation of a dental pathogen Streptococcus mutans by exposing it to fructose and other important stress agents. Further supported by growth, persistence, and competition assays, our findings revealed the ability of fructose to activate a set of stress-related functions that may prove critical to the ability of the bacterium to persist and cause diseases both within and without the oral cavity.}, }
@article {pmid40238826, year = {2025}, author = {Lee, J and Kim, B}, title = {Zero inflated high dimensional compositional data with DeepInsight.}, journal = {PloS one}, volume = {20}, number = {4}, pages = {e0320832}, doi = {10.1371/journal.pone.0320832}, pmid = {40238826}, issn = {1932-6203}, mesh = {Humans ; High-Throughput Nucleotide Sequencing/methods ; *Microbiota/genetics ; Neural Networks, Computer ; Inflammatory Bowel Diseases/microbiology ; Child ; }, abstract = {Through the Human Microbiome Project, research on human-associated microbiomes has been conducted in various fields. New sequencing techniques such as Next Generation Sequencing (NGS) and High-Throughput Sequencing (HTS) have enabled the inclusion of a wide range of features of the microbiome. These advancements have also contributed to the development of numerical proxies like Operational Taxonomic Units (OTUs) and Amplicon Sequence Variants (ASVs). Studies involving such microbiome data often encounter zero-inflated and high-dimensional problems. Based on the need to address these two issues and the recent emphasis on compositional interpretation of microbiome data, we conducted our research. To solve the zero-inflated problem in compositional microbiome data, we transformed the data onto the surface of the hypersphere using a square root transformation. Then, to solve the high-dimensional problem, we modified DeepInsight, an image-generating method using Convolutional Neural Networks (CNNs), to fit the hypersphere space. Furthermore, to resolve the common issue of distinguishing between true zero values and fake zero values in zero-inflated images, we added a small value to the true zero values. We validated our approach using pediatric inflammatory bowel disease (IBD) fecal sample data and achieved an area under the curve (AUC) value of 0.847, which is higher than the previous study's result of 0.83.}, }
@article {pmid40237489, year = {2025}, author = {Rybicka, I and Kaźmierczak, Z}, title = {The human phageome: niche-specific distribution of bacteriophages and their clinical implications.}, journal = {Applied and environmental microbiology}, volume = {}, number = {}, pages = {e0178824}, doi = {10.1128/aem.01788-24}, pmid = {40237489}, issn = {1098-5336}, abstract = {Bacteriophages (phages) play a crucial role in shaping the composition and diversity of the human microbiome across various body niches. Recent advancements in high-throughput sequencing technologies have enabled comprehensive analysis of the human phageome in different body sites. This review comprehensively analyzes phage populations across major human body niches, examining their distribution and dynamics through recent metagenomic discoveries. We explore how phage-bacteria interactions within different body sites contribute to homeostasis and disease development. Emerging evidence demonstrates that phageome perturbations can serve as early indicators of various disorders, particularly in the gut microbiome. Understanding these complex microbial interactions offers promising opportunities for developing novel diagnostic markers and therapeutic approaches. However, the causal relationship between phages, bacteria, and disease development remains unclear. Further research is needed to elucidate the role of phages in human health and disease and to explore their potential as diagnostic or therapeutic tools. Understanding the intricate interactions between phages, bacteria, and the human host is crucial for unraveling the complexities of the human microbiome and its impact on health and disease.}, }
@article {pmid40237447, year = {2025}, author = {Choudoir, MJ and Ishaq, SL and Beiko, RG and Silva, DS and Allen-Vercoe, E and O'Doherty, KC}, title = {The case for microbiome stewardship: what it is and how to get there.}, journal = {mSystems}, volume = {}, number = {}, pages = {e0006225}, doi = {10.1128/msystems.00062-25}, pmid = {40237447}, issn = {2379-5077}, abstract = {Microbiomes are essential for human, animal, plant, and ecosystem health. Despite widespread recognition of the importance of microbiomes, there is little attention paid to monitoring and safeguarding microbial ecologies on policy levels. We observe that microbiomes are deteriorating owing to practices at societal levels such as pesticide use in agriculture, air and water pollution, and overuse of antibiotics. Potential policy on these issues would cross multiple domains such as public health, environmental protection, and agriculture. We propose microbiome stewardship as a foundational concept that can act across policy domains to facilitate healthy microbiomes for human and ecosystem health. We examine challenges to be addressed and steps to take toward developing meaningful microbiome stewardship.}, }
@article {pmid40236770, year = {2025}, author = {Zhang, C and Chen, Y and Duan, R and Zhang, Y and Zheng, H and Zhang, J and Zhang, T and Xu, J and Li, K and Pei, F and Duan, L}, title = {Preconception maternal gut dysbiosis affects enteric nervous system development and disease susceptibility in offspring via the GPR41-GDNF/RET/SOX10 signaling pathway.}, journal = {iMeta}, volume = {4}, number = {2}, pages = {e70012}, pmid = {40236770}, issn = {2770-596X}, abstract = {Maternal health, specifically changes in the gut microbiota, can profoundly impact offspring health; however, our understanding of how gut microbiota alterations during the preconception period influence the offspring remains limited. In this study, we investigated the impact and mechanisms of preconception maternal gut dysbiosis on the development of the enteric nervous system (ENS) in mice. We found that preconception maternal exposure to antibiotics led to the abnormal development of the ENS in offspring, increasing their susceptibility to water avoidance stress at the adult stage. Metagenomic, targeted metabolomic, and transcriptomic analyses revealed that preconception antibiotic exposure disrupted the expression of genes crucial for embryonic ENS development by altering maternal gut microbiota composition. Multi-omics analysis combined with Limosilactobacillus reuteri and propionate gestational supplementation demonstrated that the maternal gut microbiota and metabolites may influence embryonic ENS development via the GPR41-GDNF/RET/SOX10 signaling pathway. Our findings highlight the critical importance of maintaining a healthy maternal gut microbiota before conception to support normal ENS development in offspring.}, }
@article {pmid40235960, year = {2025}, author = {Basgaran, A and Lymberopoulos, E and Burchill, E and Reis-Dehabadi, M and Sharma, N}, title = {Machine learning determines the incidence of Alzheimer's disease based on population gut microbiome profile.}, journal = {Brain communications}, volume = {7}, number = {2}, pages = {fcaf059}, pmid = {40235960}, issn = {2632-1297}, abstract = {The human microbiome is a complex and dynamic community of microbes, thought to have symbiotic benefit to its host. Influences of the gut microbiome on brain microglia have been identified as a potential mechanism contributing to neurodegenerative diseases, such as Alzheimer's disease, motor neurone disease and Parkinson's disease (Boddy SL, Giovannelli I, Sassani M, et al. The gut microbiome: A key player in the complexity of amyotrophic lateral sclerosis (ALS). BMC Med. 2021;19(1):13). We hypothesize that population level differences in the gut microbiome will predict the incidence of Alzheimer's disease using machine learning methods. Cross-sectional analyses were performed in R, using two large, open-access microbiome datasets (n = 959 and n = 2012). Countries in these datasets were grouped based on Alzheimer's disease incidence and the gut microbiome profiles compared. In countries with a high incidence of Alzheimer's disease, there is a significantly lower diversity of the gut microbiome (P < 0.05). A permutational analysis of variance test (P < 0.05) revealed significant differences in the microbiome profile between countries with high versus low incidence of Alzheimer's disease with several contributing taxa identified: at a species level Escherichia coli, and at a genus level Haemophilus and Akkermansia were found to be reproducibly protective in both datasets. Additionally, using machine learning, we were able to predict the incidence of Alzheimer's disease within a country based on the microbiome profile (mean area under the curve 0.889 and 0.927). We conclude that differences in the microbiome can predict the varying incidence of Alzheimer's disease between countries. Our results support a key role of the gut microbiome in neurodegeneration at a population level.}, }
@article {pmid40235735, year = {2025}, author = {Xu, R and Yu, Y and Chen, T}, title = {Exploring the dark side of probiotics to pursue light: Intrinsic and extrinsic risks to be opportunistic pathogens.}, journal = {Current research in food science}, volume = {10}, number = {}, pages = {101044}, pmid = {40235735}, issn = {2665-9271}, abstract = {Probiotics, live microorganisms with multiple health benefits, have gained popularity for their roles in maintaining daily health and treating a variety of diseases. However, they have the potential to be opportunistic pathogens in some conditions. This review delves into the intrinsic and extrinsic risks associated with probiotics. Intrinsic risks involve the production of harmful substances, such as toxins and invasive factors, biofilm formation, bacteria emboli, antibiotic resistance with relevant genetic materials, genetic plasticity, and metabolic issues, while extrinsic risks include problems in regulatory oversight and public awareness, host health status and appropriately administration. It emphasizes the need for a balanced view of their therapeutic benefits and potential hazards, advocating for further research to understand the complex interactions between probiotics and the human microbiome, to optimize the safety and efficacy of probiotics.}, }
@article {pmid40231347, year = {2025}, author = {Hoffmanns, L and Svedberg, D and Mateus, A}, title = {Protein O-glycosylation in the Bacteroidota phylum.}, journal = {FEBS open bio}, volume = {}, number = {}, pages = {}, doi = {10.1002/2211-5463.70041}, pmid = {40231347}, issn = {2211-5463}, support = {Wallenberg Academy Fellows 2025//Knut och Alice Wallenbergs Stiftelse/ ; 2021-06602//Vetenskapsr&#xe5;det/ ; 2022-02958//Vetenskapsr&#xe5;det/ ; ProFITGut-101076015//H2020 European Research Council/ ; }, abstract = {Glycans play crucial roles in bacteria, such as providing structural integrity or enabling interactions with the ecosystem. They can be linked to lipids, peptides, or proteins. In proteins, they modify either asparagine (N-glycosylation) or serine or threonine (O-glycosylation). Species of the Bacteroidota phylum, a major component of the human microbiome and marine and soil ecosystems, have a unique type of O-glycosylation that modifies multiple noncytoplasmic proteins containing a specific amino acid sequence. Only a small number of species have currently been characterized, but within one species, generally all proteins are modified with the same glycan structure. Most species share a common inner part but differ in the sugar composition and branching of the outer part of their glycan. This suggests that the biosynthesis of the glycan occurs in two separate steps. Both the inner core and the outer glycan are likely assembled from nucleotide-activated monosaccharides on undecaprenyl phosphate on the cytoplasmic side of the inner membrane, prior to being flipped to the periplasm and transferred to the protein. A genomic locus responsible for the biosynthesis of the outer glycan has been identified, containing some conserved genes across species. Despite substantial progress in the characterization of this O-glycosylation system, its function, the overall diversity of glycan structures across the phylum, and the complete biosynthetic pathway remain mostly unknown. Due to the importance of this group of species for the human gut microbiome, elucidating these aspects can open up strategies to modulate the composition of the microbiome community toward a healthy state.}, }
@article {pmid40229539, year = {2025}, author = {Magne, F and Ruiz-Ruiz, S and Pérez-Brocal, V and Ponce, CA and Bustamante, R and Martin, VS and Gutierrez, M and Gatti, G and Vargas, SL and Moya, A}, title = {Pneumocystis jirovecii is a potential pivotal ecological driver contributing to shifts in microbial equilibrium during the early-life lower airway microbiome assembly.}, journal = {Communications biology}, volume = {8}, number = {1}, pages = {609}, pmid = {40229539}, issn = {2399-3642}, mesh = {Humans ; Infant ; *Microbiota ; *Lung/microbiology ; Female ; *Pneumocystis carinii/physiology/genetics ; Male ; RNA, Ribosomal, 16S/genetics ; Bacteria/genetics/classification ; Infant, Newborn ; }, abstract = {Early life gut microbiota is being increasingly recognized as a major contributor to short and/or long-term human health and diseases. However, little is known about these early-life events in the human microbiome of the lower respiratory tract. This study aims to investigate fungal and bacterial colonization in the lower airways over the first year of life by analyzing lung tissue from autopsied infants. The fungal and bacterial communities of lung tissue samples from 53 autopsied infants were characterized by Next-Generation Sequencing (NGS), based on universal PCR amplification of the ITS region and the 16S rRNA gene, respectively. Our study highlights a high degree of inter-individual variability in both fungal and bacterial communities inhabiting the infant lung. The lower respiratory tract microbiota is mainly composed of transient microorganisms that likely travel from the upper respiratory tract and do not establish permanent residence. However, it could also contain some genera identified as long-term inhabitants of the lung, which could potentially play a role in lung physiology or disease. At 3-4 months of age, important dynamic changes to the microbial community were observed, which might correspond to a transitional time period in the maturation of the lung microbiome. This timeframe represents a susceptibility period for the colonization of pathogens such as Pneumocystis. The asymptomatic colonization of Pneumocystis was associated with changes in the fungal and bacterial communities. These findings suggest that the period of 2-4 months of age is a "critical window" early in life. Pneumocystis jirovecii could be a potential pivotal ecological driver contributing to shifts in microbial equilibrium during the early-life lower airway microbiome assembly, and to the future health of children.}, }
@article {pmid40227812, year = {2025}, author = {Leigh, J and Skidmore, B and Wong, A and Maleki Vareki, S and Ng, TL}, title = {Exploring the Microbiome's Impact on Glioma and Brain Metastases: Insights into Development, Progression, and Treatment Response-A Scoping Review.}, journal = {Cancers}, volume = {17}, number = {7}, pages = {}, doi = {10.3390/cancers17071228}, pmid = {40227812}, issn = {2072-6694}, abstract = {Background: The human microbiome plays a crucial role in health and disease. Dysbiosis, an imbalance of microorganisms, has been implicated in cancer development and treatment response, including in primary brain tumors and brain metastases, through interactions mediated by the gut-brain axis. This scoping review synthesizes current evidence on the relationship between the human microbiome and brain tumors. Methods: A systematic search of five electronic databases was conducted by an expert librarian, using controlled vocabulary and keywords. A targeted grey literature search in Google Scholar and clinical trial registries was also undertaken. Eligible studies included primary research involving human patients, or in vivo, or in vitro models of glioma or brain metastasis, with a focus on the microbiome's role in tumor development, treatment response, and outcomes. Results: Out of 584 citations screened, 40 studies met inclusion criteria, comprising 24 articles and 16 conference abstracts. These included 12 human studies, 16 using mouse models, 7 combining both, and 5 employing large datasets or next-generation sequencing of tumor samples. Thirty-one studies focused on primary brain tumors, six on brain metastases, and three on both. Of the 20 studies examining dysbiosis in tumor development, 95% (n = 19) found an association with tumor growth. Additionally, 71.4% (n = 5/7) of studies reported that microbiome alterations influenced treatment efficacy. Conclusions: Although the role of the gut-brain axis in brain tumors is still emerging and is characterized by heterogeneity across studies, existing evidence consistently supports a relationship between the gut microbiome and both brain tumor development and treatment outcomes.}, }
@article {pmid40219702, year = {2025}, author = {Xiao, Y and Yue, X and Zhang, X and Yang, Y and Zhang, Y and Sun, L}, title = {The role of bacteriophage in inflammatory bowel disease and its therapeutic potential.}, journal = {Critical reviews in microbiology}, volume = {}, number = {}, pages = {1-15}, doi = {10.1080/1040841X.2025.2492154}, pmid = {40219702}, issn = {1549-7828}, abstract = {Inflammatory bowel disease (IBD) refers to a group of chronic inflammatory disorders impacting the gastrointestinal (GI) tract. It represents a significant public health challenge due to its rising global incidence and substantial impact on patients' quality of life. Emerging research suggests a pivotal role of the human microbiome in IBD pathogenesis. Bacteriophages, integral components of the human microbiome, are indicated to influence the disease onset, progression, and therapeutic strategies. Here, we review the effect of bacteriophages on the pathogenesis of IBD and, more specifically, on the gut bacteria, the systemic immunity, and the susceptibility genes. Additionally, we explore the potential therapeutic use of the bacteriophages to modify gut microbiota and improve the health outcomes of IBD patients. This review highlights the potential of therapeutic bacteriophages in regulating gut microbiota and modulating the immune response to improve health outcomes in IBD patients. Future studies on personalized bacteriophage therapy and its integration into clinical practice could advance treatment strategies for IBD.}, }
@article {pmid40214493, year = {2025}, author = {Rahim, MA and Seo, H and Barman, I and Hossain, MS and Shuvo, MSH and Song, HY}, title = {Insights into Autophagy in Microbiome Therapeutic Approaches for Drug-Resistant Tuberculosis.}, journal = {Cells}, volume = {14}, number = {7}, pages = {}, doi = {10.3390/cells14070540}, pmid = {40214493}, issn = {2073-4409}, support = {RS-2023-00219563//National Research Foundation of Korea/ ; P248400003//Korea Institute for Advancement of Technology (KIAT)/ ; Soonchunhyang University Research Fund//Soonchunhyang University/ ; }, mesh = {Humans ; *Autophagy ; *Tuberculosis, Multidrug-Resistant/therapy/microbiology ; *Microbiota ; Mycobacterium tuberculosis/drug effects ; Animals ; Antitubercular Agents/therapeutic use/pharmacology ; }, abstract = {Tuberculosis, primarily caused by Mycobacterium tuberculosis, is an airborne lung disease and continues to pose a significant global health threat, resulting in millions of deaths annually. The current treatment for tuberculosis involves a prolonged regimen of antibiotics, which leads to complications such as recurrence, drug resistance, reinfection, and a range of side effects. This scenario underscores the urgent need for novel therapeutic strategies to combat this lethal pathogen. Over the last two decades, microbiome therapeutics have emerged as promising next-generation drug candidates, offering advantages over traditional medications. In 2022, the Food and Drug Administration approved the first microbiome therapeutic for recurrent Clostridium infections, and extensive research is underway on microbiome treatments for various challenging diseases, including metabolic disorders and cancer. Research on microbiomes concerning tuberculosis commenced roughly a decade ago, and the scope of this research has broadened considerably over the last five years, with microbiome therapeutics now viewed as viable options for managing drug-resistant tuberculosis. Nevertheless, the understanding of their mechanisms is still in its infancy. Although autophagy has been extensively studied in other diseases, research into its role in tuberculosis is just beginning, with preliminary developments in progress. Against this backdrop, this comprehensive review begins by succinctly outlining tuberculosis' characteristics and assessing existing treatments' strengths and weaknesses, followed by a detailed examination of microbiome-based therapeutic approaches for drug-resistant tuberculosis. Additionally, this review focuses on establishing a basic understanding of microbiome treatments for tuberculosis, mainly through the lens of autophagy as a mechanism of action. Ultimately, this review aims to contribute to the foundational comprehension of microbiome-based therapies for tuberculosis, thereby setting the stage for the further advancement of microbiome therapeutics for drug-resistant tuberculosis.}, }
@article {pmid40211685, year = {2025}, author = {Kim, JW and Choi, EC and Lee, KJ}, title = {Standardizing the approach to clinical-based human microbiome research: from clinical information collection to microbiome profiling and human resource utilization.}, journal = {Osong public health and research perspectives}, volume = {}, number = {}, pages = {}, doi = {10.24171/j.phrp.2024.0319}, pmid = {40211685}, issn = {2210-9099}, abstract = {OBJECTIVES: This study presents the standardized protocols developed by the Clinical-Based Human Microbiome Research and Development Project (cHMP) in the Republic of Korea.<br><br>METHODS: It addresses clinical metadata collection, specimen handling, DNA extraction, sequencing methods, and quality control measures for microbiome research.<br><br>RESULTS: The cHMP involves collecting samples from healthy individuals and patients across various body sites, including the gastrointestinal tract, oral cavity, respiratory system, urogenital tract, and skin. These standardized procedures ensure consistent data quality through controlled specimen collection, storage, transportation, DNA extraction, and sequencing. Sequencing encompasses both amplicon and whole metagenome methods, followed by stringent quality checks. The protocols conform to international guidelines, ensuring that the data generated are both reliable and comparable across microbiome studies.<br><br>CONCLUSION: The cHMP underscores the importance of methodological standardization in enhancing data integrity, reproducibility, and advancing microbiome-based research with potential applications for improving human health outcomes.}, }
@article {pmid40207916, year = {2025}, author = {Lebrun-Corbin, M and Cheung, BH and Hullahalli, K and Dailey, KG and Bailey, K and Waldor, MK and Wunderink, RG and Bachta, KER and Hauser, AR}, title = {Pseudomonas aeruginosa population dynamics in a vancomycin-induced murine model of gastrointestinal carriage.}, journal = {mBio}, volume = {}, number = {}, pages = {e0313624}, doi = {10.1128/mbio.03136-24}, pmid = {40207916}, issn = {2150-7511}, abstract = {UNLABELLED: Pseudomonas aeruginosa is a common nosocomial pathogen and a major cause of morbidity and mortality in hospitalized patients. Multiple reports highlight that P. aeruginosa gastrointestinal colonization may precede systemic infections by this pathogen. Gaining a deeper insight into the dynamics of P. aeruginosa gastrointestinal carriage is an essential step in managing gastrointestinal colonization and could contribute to preventing bacterial transmission and progression to systemic infection. Here, we present a clinically relevant mouse model relying on parenteral vancomycin pretreatment and a single orogastric gavage of a controlled dose of P. aeruginosa. Robust carriage was observed with multiple clinical isolates, and carriage persisted for up to 60 days. Histological and microbiological examination of mice indicated that this model indeed represented carriage and not infection. We then used a barcoded P. aeruginosa library along with the sequence tag-based analysis of microbial populations (STAMPR) analytic pipeline to quantify bacterial population dynamics and bottlenecks during the establishment of the gastrointestinal carriage. Analysis indicated that most of the P. aeruginosa population was rapidly eliminated in the stomach, but the few bacteria that moved to the small intestine and the cecum expanded rapidly. Hence, the stomach constitutes a significant barrier against gastrointestinal carriage of P. aeruginosa, which may have clinical implications for hospitalized patients.<br><br>IMPORTANCE: While Pseudomonas aeruginosa is rarely part of the normal human microbiome, carriage of the bacterium is quite frequent in hospitalized patients and residents of long-term care facilities. P. aeruginosa carriage is a precursor to infection. Options for treating infections caused by difficult-to-treat P. aeruginosa strains are dwindling, underscoring the urgency to better understand and impede pre-infection stages, such as colonization. Here, we use vancomycin-treated mice to model antibiotic-treated patients who become colonized with P. aeruginosa in their gastrointestinal tracts. We identify the stomach as a major barrier to the establishment of gastrointestinal carriage. These findings suggest that efforts to prevent gastrointestinal colonization should focus not only on judicious use of antibiotics but also on investigation into how the stomach eliminates orally ingested P. aeruginosa.}, }
@article {pmid40207286, year = {2025}, author = {Ronkainen, A and Khan, I and Satokari, R}, title = {Pathogen exclusion from intestinal mucus and antimicrobial susceptibility of Bifidobacterium spp. strains from fecal donors.}, journal = {Microbiome research reports}, volume = {4}, number = {1}, pages = {5}, pmid = {40207286}, issn = {2771-5965}, abstract = {Aim: To study the ability of bifidobacterial strains isolated from fecal donors to prevent pathogens from adhering to intestinal mucus, along with their antimicrobial susceptibility. Methods: Pathogen prevention was assessed through an in vitro adhesion assay using immobilized porcine mucus. Subsequently, bifidobacterial RNA-Seq data were analyzed to pinpoint glycoside hydrolases and glycosyltransferases possibly involved in mucus degradation affecting pathogen adhesion. The antimicrobial susceptibility of bifidobacterial strains was evaluated using in vitro susceptibility testing, followed by analysis of whole-genome sequencing data to reveal antimicrobial resistance genes. Results: Bifidobacterial strains inhibited pathogen adhesion to intestinal mucus, with most strains reducing the adhesion levels of pathogens like Escherichia coli, Listeria monocytogenes, Salmonella Typhimurium, and Staphylococcus aureus by at least 70%. None of the strains significantly affected Pseudomonas aeruginosa, but they moderately reduced the adhesion of Yersinia enterocolitica. Gene expression analysis indicated that the more effective strains expressed higher levels of glycoside hydrolases, correlating with their pathogen exclusion capabilities. Antimicrobial susceptibility testing revealed that most strains were sensitive to several antibiotics, though some exhibited resistance to tobramycin, trimethoprim, and ciprofloxacin. Notably, one strain carried the tetW gene, conferring resistance to tetracycline. Conclusion: The bifidobacterial strains characterized in this study show potential for bacteriotherapeutic applications due to their strong ability to interfere with the adhesion of pathogenic bacteria and their lack of alarming antimicrobial resistance patterns.}, }
@article {pmid40207282, year = {2025}, author = {Stuivenberg, GA and Poon, A and Burton, JP and Spence, JD}, title = {Potential effects of probiotics on atherosclerosis.}, journal = {Microbiome research reports}, volume = {4}, number = {1}, pages = {11}, pmid = {40207282}, issn = {2771-5965}, abstract = {The rising global incidence of atherosclerosis highlights the inadequacies in our understanding of the pathophysiology and treatment of the disease. Increasing evidence outlines the importance of the intestinal microbiome in atherosclerosis, wherein gut-derived uremic toxins (GDUTs) may be of concern. Plasma levels of the GDUTs trimethylamine n-oxide (TMAO), p-cresyl sulfate, and indoxyl sulfate are associated with accelerated renal function decline and increased cardiovascular risk. Thus, reducing the amount of GDUTs in circulation is expected to benefit patients with atherosclerosis. Because some beneficial bacteria can clear GDUTs in vitro and in vivo, orally administered probiotics targeting the intestinal tract represent a promising way to bring about these changes. Atherosclerosis such, this perspective reviews the potential use of probiotics to treat atherosclerosis, particularly in patients with non-traditional risk factors and/or impaired renal function.}, }
@article {pmid40207275, year = {2025}, author = {Horwell, E and Bearn, P and Cutting, SM}, title = {A microbial symphony: a literature review of the factors that orchestrate the colonization dynamics of the human colonic microbiome during infancy and implications for future health.}, journal = {Microbiome research reports}, volume = {4}, number = {1}, pages = {1}, pmid = {40207275}, issn = {2771-5965}, abstract = {Since the advent of new sequencing and bioinformatic technologies, our understanding of the human microbiome has expanded rapidly over recent years. Numerous studies have indicated causal links between alterations to the microbiome and a range of pathological conditions. Furthermore, a large body of epidemiological data is starting to suggest that exposure, or lack thereof, to specific microbial species during the first five years of life has key implications for long-term health outcomes. These include chronic inflammatory and metabolic conditions such as diabetes, asthma, inflammatory bowel disease (IBD), and obesity, with the effects lasting into adulthood. Human microbial colonisation during these first five years of life is a highly dynamic process, with multiple environmental exposures recently being characterised to have influence before the microbiome stabilises and resembles that of an adult at 3-5 years. This short period of time, known as the window of opportunity, appears to "prime" immunoregulation for later life. Understanding and appreciating this aspect of human physiology is therefore crucial for clinicians, scientists, and public health officials. This review outlines the most recent evidence for the pre- and post-natal environments that order the development of the microbiome, how these influences metabolic and immunoregulatory pathways, and their associated health outcomes. It also discusses the limitations of the current knowledge base, and describes the potential microbiome-mediated interventions and public health measures that may have therapeutic potential in the future.}, }
@article {pmid40207273, year = {2025}, author = {van Beek, N and Katavisto, I and Lehto, M and Kolho, KL and de Vos, WM and Salonen, A and Korpela, K}, title = {Host-microbiota interactions in the infant gut revealed by daily faecal sample time series.}, journal = {Microbiome research reports}, volume = {4}, number = {1}, pages = {13}, pmid = {40207273}, issn = {2771-5965}, abstract = {Aim: This study aims to explore the interplay between host immune factors and gut microbiota in human infants in vivo using time-series daily stool samples and identify biomarkers of host-microbe interactions. Methods: 216 faecal samples collected from infants aged 5-6 or 11-12 months were analysed for gut microbiota composition, total bacterial load, and biomarkers of immune function. Results: We identified indications of microbial stimulation of eosinophil cationic protein (ECP), IgA, calprotectin (Cal), intestinal alkaline phosphatase (IAP), and Bactericidal/permeability-increasing protein (BPI) at 6 and 12 months, as well as stimulation of lipocalin 2 (LCN2), lactoferrin (LTF), and alpha-defensin-5 only at 6 months. The associations between biomarker concentrations and bacterial population growth were primarily positive at 6 months and mostly negative at 12 months, suggesting increasing host regulation of the microbiota with age. The exceptions were IAP, which was predictive of declining bacterial populations at both time points, and Cal, whose associations changed from negative at 6 months to positive at 12 months. Conclusion: There is an age-associated development in the correlation pattern between bacterial population growth and the biomarker concentrations, suggesting that host-microbe interactions change during early development. Albumin appeared as a potential marker of gut permeability, while LCN2 seemed to correlate with gut transit time. Mucin degradation appeared to decrease with age. Mucin2 and IAP emerged as potentially important regulators of the bacterial populations in the infant gut. The study demonstrates the utility of biomarker and bacteria profiling from daily stool samples for analysing in vivo associations between the immune system and the gut microbiota and provides evidence of host regulation of the microbiota in infants.}, }
@article {pmid40195307, year = {2025}, author = {Zhang, J and Yang, J and Luo, J and Wu, W and Luo, H and Wei, W and Lyu, H and Wang, Y and Yi, H and Zhang, Y and Fan, Z and Lyu, H and Kanakaveti, VP and Qin, B and Yuan, P and Yang, R and Zhang, H and Zuo, T and Felsher, DW and Lee, MH and Li, K}, title = {Lactobacillus acidophilus potentiates oncolytic virotherapy through modulating gut microbiota homeostasis in hepatocellular carcinoma.}, journal = {Nature communications}, volume = {16}, number = {1}, pages = {3315}, pmid = {40195307}, issn = {2041-1723}, support = {2023A1515030245//Natural Science Foundation of Guangdong Province (Guangdong Natural Science Foundation)/ ; 2023A1515010737//Natural Science Foundation of Guangdong Province (Guangdong Natural Science Foundation)/ ; 82473321//National Natural Science Foundation of China (National Science Foundation of China)/ ; 82204411//National Natural Science Foundation of China (National Science Foundation of China)/ ; 82373139//National Natural Science Foundation of China (National Science Foundation of China)/ ; }, mesh = {Animals ; *Gastrointestinal Microbiome/physiology ; *Lactobacillus acidophilus/metabolism/physiology ; *Carcinoma, Hepatocellular/therapy/microbiology ; *Liver Neoplasms/therapy/microbiology ; *Oncolytic Virotherapy/methods ; Mice ; Female ; Homeostasis ; Humans ; Oncolytic Viruses/genetics ; Mice, Inbred C57BL ; Dysbiosis/microbiology ; Cell Line, Tumor ; STAT3 Transcription Factor/metabolism ; Signal Transduction ; }, abstract = {Oncolytic viruses (OVs) hold promise for cancer treatment. However, the antitumor efficacy is limited. Microbiota plays a pivotal role in cancer treatment and its impact on oncolytic virotherapy is unknown. Here, we show that VSVΔ51 has higher antitumor efficacy for hepatocellular carcinoma in the absence of microbiota in female mouse models. VSVΔ51 infection causes microbiota dysbiosis, increasing most of the gut bacteria abundance, while decreasing the commensal Lactobacillus. VSVΔ51 reduced intestinal expression of SLC20A1 that binds to Lactobacillus acidophilus (L. acidophilus) CdpA cell wall protein through IL6-JAK-STAT3 signaling, thereby attenuating attachment and colonization of L. acidophilus. L. acidophilus supplementation confers sensitivity to VSVΔ51 through restoring gut barrier integrity and microbiota homeostasis destroyed by VSVΔ51. In this work, we show that targeting microbiota homostasis holds substantial potential in improving therapeutic outcomes of oncolytic virotherapy.}, }
@article {pmid40193328, year = {2025}, author = {Jagadesan, S and Guda, C}, title = {MetaDAVis: An R shiny application for metagenomic data analysis and visualization.}, journal = {PloS one}, volume = {20}, number = {4}, pages = {e0319949}, doi = {10.1371/journal.pone.0319949}, pmid = {40193328}, issn = {1932-6203}, mesh = {*Metagenomics/methods ; Humans ; RNA, Ribosomal, 16S/genetics ; *Software ; *Metagenome ; Microbiota/genetics ; High-Throughput Nucleotide Sequencing ; }, abstract = {The human microbiome exerts tremendous influence on maintaining a balance between human health and disease. High-throughput sequencing has enabled the study of microbial communities at an unprecedented resolution. Generation of massive amounts of sequencing data has also presented novel challenges to analyzing and visualizing data to make biologically relevant interpretations. We have developed an interactive Metagenome Data Analysis and Visualization (MetaDAVis) tool for 16S rRNA as well as the whole genome sequencing data analysis and visualization to address these challenges using an R Shiny application. MetaDAVis can perform six different types of analyses that include: i) Taxonomic abundance distribution; ii) Alpha and beta diversity analyses; iii) Dimension reduction tasks using PCA, t-SNE, and UMAP; iv) Correlation analysis using taxa- or sample-based data; v) Heatmap generation; and vi) Differential abundance analysis. MetaDAVis creates interactive and dynamic figures and tables from multiple methods enabling users to easily understand their data using different variables. Our program is user-friendly and easily customizable allowing those without any programming background to perform comprehensive data analyses using a standalone or web-based interface.}, }
@article {pmid40192037, year = {2025}, author = {Verma, M and Randhawa, S and Bathla, M and Teji, N and Acharya, A}, title = {Strategic use of nanomaterials as double-edged therapeutics to control carcinogenesis via regulation of dysbiosis and bacterial infection: current status and future prospects.}, journal = {Journal of materials chemistry. B}, volume = {}, number = {}, pages = {}, doi = {10.1039/d4tb02409e}, pmid = {40192037}, issn = {2050-7518}, abstract = {The human microbiome plays a crucial role in modulating health and disease susceptibility through a complex network of interactions with the host. When the delicate balance of this microbial ecosystem is disrupted, it often correlates with the onset of systemic diseases. An over-abundance of pathogenic microorganisms within the microbiome has been implicated as a driving factor in the development of disease conditions such as diabetes, obesity, and chronic infections. It has been observed that microbiome dysbiosis perturbs metabolic, inflammatory, and immunological pathways, potentially facilitating carcinogenesis. Furthermore, the metabolites associated with microbial dysbiosis exert multifaceted effects, including metabolic interference, host DNA damage, and tumor promotion, further underscoring the microbiome's significance in several of the cancers. This new exploration of microbiome involvement in carcinogenesis needs additional patient sample analysis, which could provide new insights into cancer diagnosis and treatment. However, treating these diseases using drugs, traditional methods, etc. has resulted in multi-drug resistance, and this has eventually made the situation worrisome. This review highlights the importance of nanotechnology, which may tackle these pathogenic conditions simultaneously by targeting common receptors present in bacteria and cancer. Herein, we have explained how nanotechnology may come to the forefront for these treatments. It explores the potential of non-antibiotic disinfectants, i.e., nanoparticles (NPs) with dual targeting capabilities against microbes and cancer cells, using mechanisms such as ROS generation and DNA damage while minimizing the chances of drug resistance.}, }
@article {pmid40191210, year = {2025}, author = {Karisola, P and Kanerva, M and Vuokko, A and Liira, H and Wang, S and Kvarnström, K and Varonen, M and Suojalehto, H and Alenius, H}, title = {Patients with post-COVID-19 condition show minor blood transcriptomic changes, with altered erythrocyte gene expression in a male subgroup.}, journal = {Frontiers in immunology}, volume = {16}, number = {}, pages = {1500997}, pmid = {40191210}, issn = {1664-3224}, mesh = {Humans ; *COVID-19/genetics/blood/immunology/complications ; Male ; Middle Aged ; *Transcriptome ; *SARS-CoV-2 ; Aged ; *Erythrocytes/metabolism ; Female ; Adult ; Gene Expression Profiling ; Leukocytes, Mononuclear/metabolism ; Quality of Life ; }, abstract = {BACKGROUND: The mechanisms underlying persistent symptoms after non-severe COVID-19 remain unclear. This study aimed to investigate transcriptomic changes in peripheral blood cells of patients with post-COVID-19 condition (PCC) and assess if distinct clinical subtypes with specific gene signatures could be identified.<br><br>METHODS: The cohort included 111 PCC patients from the SARS-CoV-2 Omicron variant era, with 57 recovered (Recov) and 54 having prolonged symptoms indicative of PCC. The results were compared to 63 healthy controls (Ctrl) without known SARS-CoV-2 infection. Clinical data included patient assessments, laboratory results, comorbidities, and questionnaires on quality of life and functioning. Transcriptomic analysis and cellular deconvolution methods were used on total RNA from peripheral blood mononuclear cells (PBMCs).<br><br>RESULTS: PCC patients had more comorbidities (mean 1.3) and more frequently (59%) at least one comorbidity than recovered patients (31%) and controls (24%). Overall, past COVID-19 illness or current PCC symptoms caused minimal changes in the blood cell transcriptome, with only 3-6 differentially expressed genes (DEGs) identified across comparisons. However, a subset of male PCC patients exhibited an increased fraction of deconvoluted erythroblasts and significant genome-wide gene expression changes, with 399 DEGs compared to recovered and control males. These genes were enriched in pathways related to heme metabolism and gas exchange in erythrocytes.<br><br>CONCLUSIONS: Persistent symptoms in PCC are multifactorial and not directly linked to peripheral blood cell gene expression changes. However, a subgroup of male PCC patients shows distinct erythrocyte responses that may contribute to long-term symptoms.}, }
@article {pmid40190580, year = {2025}, author = {Delicati, A and Marcante, B and Catelan, D and Biggeri, A and Caenazzo, L and Tozzo, P}, title = {Hand-to-surface bacterial transfer and healthcare-associated infections prevention: a pilot study on skin microbiome in a molecular biology laboratory.}, journal = {Frontiers in medicine}, volume = {12}, number = {}, pages = {1546298}, pmid = {40190580}, issn = {2296-858X}, abstract = {BACKGROUND: Healthcare-associated infections (HAIs) are a major global public health problem, contributing significantly to patient morbidity and mortality. This study analyses differences in type and amounts of bacteria transferred from volunteers' dominant palm to two healthcare-relevant surfaces (glass and laminate table), both before and after hand washing with water and antibacterial soap. The aim was to understand hand-to-surface microbial contamination and support the development of HAI prevention strategies.<br><br>METHODS: Microbial DNA was extracted and sequenced to identify bacteria species. Taxonomic and statistical analyses were performed to evaluate bacterial diversity and abundance across the experimental groups.<br><br>RESULTS: The results confirmed greater bacteria abundance and species richness on palm compared to surfaces, with a significant reduction after hand washing, especially on glass. Taxa analysis highlighted the increased persistence of Gram-negative HAIs-related bacteria on laminate surface, while Gram-positive opportunistic bacteria were more abundant on palms and glass surface. Beta diversity confirmed significant differences in microbial composition between the groups, highlighting the importance of bacteria-surface characteristics in designing preventive measures.<br><br>CONCLUSION: Despite some limitations, our study emphasizes the importance of microbiological surveillance for all opportunistic bacteria with pathogenic potential. These findings can contribute to more effective guidelines for surface disinfection and hand washing, key elements in preventing HAIs.}, }
@article {pmid40188410, year = {2025}, author = {Oyovwi, MO and Ben-Azu, B and Babawale, KH}, title = {Therapeutic potential of microbiome modulation in reproductive cancers.}, journal = {Medical oncology (Northwood, London, England)}, volume = {42}, number = {5}, pages = {152}, pmid = {40188410}, issn = {1559-131X}, mesh = {Humans ; *Microbiota ; Probiotics/therapeutic use ; Female ; Dysbiosis/microbiology/therapy ; *Genital Neoplasms, Female/microbiology/therapy ; Fecal Microbiota Transplantation/methods ; Animals ; Gastrointestinal Microbiome ; }, abstract = {The human microbiome, a complex ecosystem of microbial communities, plays a crucial role in physiological processes, and emerging research indicates a potential link between it and reproductive cancers. This connection highlights the significance of understanding the microbiome's influence on cancer development and treatment. A comprehensive review of current literature was conducted, focusing on studies that investigate the relationship between microbiome composition, reproductive cancer progression, and potential therapeutic approaches to modulate the microbiome. Evidence suggests that imbalances in the microbiome, known as dysbiosis, may contribute to the development and progression of reproductive cancers. Specific microbial populations have been associated with inflammatory responses, immune modulation, and even resistance to conventional therapies. Interventions such as probiotics, dietary modifications, and fecal microbiota transplantation have shown promise in restoring healthy microbiome function and improving cancer outcomes in pre-clinical models, with pilot studies in humans indicating potential benefits. This review explores the therapeutic potential of microbiome modulation in the management of reproductive cancers, discussing the mechanisms involved and the evidence supporting microbiome-targeted therapies. Future research is warranted to unravel the complex interactions between the microbiome and reproductive cancer pathophysiology, paving the way for innovative approaches.}, }
@article {pmid40177558, year = {2025}, author = {Xia, S and Jiang, D and Zhou, Q and Lyu, H and Voigt, AY and Zhou, X and Zhou, Z and Huang, Y}, title = {Unlocking the healthy human microbiome: Redefining core microbial signatures.}, journal = {Acta pharmaceutica Sinica. B}, volume = {15}, number = {2}, pages = {1189-1192}, doi = {10.1016/j.apsb.2025.01.001}, pmid = {40177558}, issn = {2211-3835}, }
@article {pmid40174574, year = {2025}, author = {Zeng, S and Almeida, A and Mu, D and Wang, S}, title = {Embracing the unknown: Proteomic insights into the human microbiome.}, journal = {Cell metabolism}, volume = {37}, number = {4}, pages = {799-801}, doi = {10.1016/j.cmet.2025.02.003}, pmid = {40174574}, issn = {1932-7420}, abstract = {Protein-level investigations into the human microbiome provide insights into active microbial functions. Recently, Valdés-Mas et al.[1] introduced a metagenome-informed metaproteomics approach to functionally explore species-level microbiome-host interactions and quantify the dietary exposome. Its potential has been implemented in mice and humans to uncover proteomic signatures of health and inflammatory bowel disease.}, }
@article {pmid40170399, year = {2025}, author = {Schütz, B and Krause, FF and Taudte, RV and Zaiss, MM and Luu, M and Visekruna, A}, title = {Modulation of Host Immunity by Microbiome-Derived Indole-3-Propionic Acid and Other Bacterial Metabolites.}, journal = {European journal of immunology}, volume = {55}, number = {4}, pages = {e202451594}, doi = {10.1002/eji.202451594}, pmid = {40170399}, issn = {1521-4141}, support = {VI562/7-1//Deutsche Forschungsgemeinschaft/ ; }, mesh = {Humans ; *Gastrointestinal Microbiome/immunology ; *Indoles/immunology ; Animals ; Immunity, Mucosal/immunology ; Dysbiosis/immunology ; Bacteria/immunology/metabolism ; Propionates ; }, abstract = {In recent years, we have witnessed a rapidly growing interest in the intricate communications between intestinal microorganisms and the host immune system. Research on the human microbiome is evolving from merely descriptive and correlative studies to a deeper mechanistic understanding of the bidirectional interactions between gut microbiota and the mucosal immune system. Despite numerous challenges, it has become increasingly evident that an imbalance in gut microbiota composition, known as dysbiosis, is associated with the development and progression of various metabolic, immune, cancer, and neurodegenerative disorders. A growing body of evidence highlights the importance of small molecules produced by intestinal commensal bacteria, collectively referred to as gut microbial metabolites. These metabolites serve as crucial diffusible messengers, translating the microbial language to host cells. This review aims to explore the complex and not yet fully understood molecular mechanisms through which microbiota-derived metabolites influence the activity of the immune cells and shape immune reactions in the gut and other organs. Specifically, we will discuss recent research that reveals the close relationship between microbial indole-3-propionic acid (IPA) and mucosal immunity. Furthermore, we will emphasize the beneficial effects of IPA on intestinal inflammation and discuss its potential clinical implications.}, }
@article {pmid40166311, year = {2025}, author = {Inglis, LK and Grigson, SR and Roach, MJ and Edwards, RA}, title = {Prophages as a source of antimicrobial resistance genes in the human microbiome.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2025.03.19.644263}, pmid = {40166311}, issn = {2692-8205}, abstract = {UNLABELLED: Prophages-viruses that integrate into bacterial genomes-are ubiquitous in the microbial realm. Prophages contribute significantly to horizontal gene transfer, including the potential spread of antimicrobial resistance (AMR) genes, because they can collect host genes. Understanding their role in the human microbiome is essential for fully understanding AMR dynamics and possible clinical implications. We analysed almost 15,000 bacterial genomes for prophages and AMR genes. The bacteria were isolated from diverse human body sites and geographical regions, and their genomes were retrieved from GenBank. AMR genes were detected in 6.6% of bacterial genomes, with a higher prevalence in people with symptomatic diseases. We found a wide variety of AMR genes combating multiple drug classes. We discovered AMR genes previously associated with plasmids, such as blaOXA-23 in Acinetobacter baumannii prophages or genes found in prophages in species they had not been previously described in, such as mefA-msrD in Gardnerella prophages, suggesting prophage-mediated gene transfer of AMR genes. Prophages encoding AMR genes were found at varying frequencies across body sites and geographical regions, with Asia showing the highest diversity of AMR genes.<br><br>IMPORTANCE: Antimicrobial resistance (AMR) is a growing threat to public health, and understanding how resistance genes spread between bacteria is essential for controlling their dissemination. Bacteriophages, viruses that infect bacteria, have been recognised as potential vehicles for transferring these resistance genes, but their role in the human microbiome remains poorly understood. We examined nearly 15,000 bacterial genomes from various human body sites and regions worldwide to investigate how often prophages carry AMR genes in the human microbiome. Although AMR genes were uncommon in prophages, we identified diverse resistance genes across multiple bacterial species and drug classes, including some typically associated with plasmids. These findings reveal that prophages may contribute to the spread of resistance genes, highlighting an overlooked mechanism in the dynamics of AMR transmission. Ongoing monitoring of prophages is critical to fully understanding the pathways through which resistance genes move within microbial communities and impact human health.}, }
@article {pmid40166302, year = {2025}, author = {Walker, AR and Pham, DN and Noeparvar, P and Peterson, AM and Lipp, MK and Lemos, JA and Zeng, L}, title = {FRUCTOSE ACTIVATES A STRESS RESPONSE SHARED BY METHYLGLYOXAL AND HYDROGEN PEROXIDE IN STREPTOCOCCUS MUTANS.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2024.10.26.620100}, pmid = {40166302}, issn = {2692-8205}, abstract = {Fructose catabolism by Streptococcus mutans is initiated by three PTS transporters yielding either fructose-1-phoshate (F-1-P) or fructose-6-phosphate (F-6-P). Deletion of one such F-1-P-generating PTS, fruI, has been shown to reduce the cariogenicity of S. mutans in rats fed a high-sucrose diet. Moreover, a recent study linked fructose metabolism in S. mutans to a reactive electrophile species (RES) methylglyoxal. Here, we conducted a comparative transcriptomic analysis of exponentially grown S. mutans shocked with 50 mM fructose, 50 mM glucose, 5 mM methylglyoxal, or 0.5 mM hydrogen peroxide (H2O2). The results revealed a striking overlap between the fructose and methylglyoxal transcriptomes, totaling 176 genes, 61 of which were also shared with the H2O2 transcriptome. This core of 61 genes encompassed many of the same pathways affected by exposure to low pH or zinc intoxication. Consistent with these findings, fructose negatively impacted metal homeostasis of a mutant deficient in zinc expulsion and the growth of a mutant of the major oxidative stress regulator SpxA1. We further demonstrated the induction of the superoxide dismutase (sodA) and the fruRKI operon by different levels of fructose. Finally, fructose metabolism lowered culture pH at a faster pace, allowed better survival under acidic and nutrient-depleted conditions, and enhanced the competitiveness of S. mutans against Streptococcus sanguinis, although a moderated level of F-1-P might further boost some of these benefits. In conclusion, fructose metabolism is integrated into the stress core of S. mutans and regulates critical functions required for survival in both the oral cavity and during systemic infections. Importance. Fructose is a common monosaccharide in the biosphere, yet its overconsumption has been linked to various health problems in humans including insulin resistance, obesity, diabetes, and non-alcoholic liver diseases. These effects are in large part attributed to the unique biochemical characteristics and metabolic responses associated with the degradation of fructose. Yet, an understanding of the effects of fructose on the physiology of bacteria and its implications to the human microbiome is severely lacking. Here we performed a series of analyses on the gene regulation of a dental pathogen Streptococcus mutans by exposing it to fructose and other important stress agents. Further supported by growth, persistence, and competition assays, our findings revealed the ability of fructose to activate a set of cellular functions that may prove critical to the ability of the bacterium to persist and cause diseases both within and without of the oral cavity.}, }
@article {pmid40162761, year = {2025}, author = {Jung, M and Boutin, S and Simon, MM and Frese, C}, title = {Comparative analysis of oral microbiome in molar-incisor-hypomineralization vs healthy age-matched controls.}, journal = {Microbiology spectrum}, volume = {}, number = {}, pages = {e0289724}, doi = {10.1128/spectrum.02897-24}, pmid = {40162761}, issn = {2165-0497}, abstract = {UNLABELLED: Molar-incisor-hypomineralization (MIH) is one of the most challenging dental diseases in children. While the association of oral microbiomes with caries and periodontitis has been studied thoroughly, limited data on the microbial composition in MIH and its clinical significance exist. This cross-sectional study aimed to compare the supragingival plaque microbiome between children and adolescents affected by MIH and a healthy age-matched control group. Ninety-five patients aged 7-17 years were recruited at the Department of Conservative Dentistry, Heidelberg University Hospital. The final sample included 29 participants with a confirmed diagnosis of MIH, treated preventively and restoratively, and 35 orally healthy controls. Clinical data were obtained, and supragingival plaque samples were collected using OMNIgene ORAL OMR-110 (DNA Genotek Inc.), followed by 16S rRNA amplicon sequencing. The microbiome composition was analyzed using α-diversity (Shannon index) and evenness (Pielou index), with group differences assessed using permutational multivariate analysis of variance (PERMANOVA) and MaAsLin2. The overall microbiome composition showed mostly similarities between both groups (PERMANOVA: R[2] = 0.019, P-value = 0.287), indicating no major dysbiosis. However, a significant decrease in α-diversity and evenness was observed with an increasing number of MIH-affected teeth. Pronounced positive correlations were found between ASV0055 (Streptococcus spp.), caries experience, and MIH severity. ASV0100 (Mannheimia sp.) increased significantly with the increasing number of MIH-affected teeth, whereas ASV0053 (Bergeyella sp.) decreased with higher caries experience. In summary, the oral microbiome of children and adolescents with MIH exhibits no significant differences from healthy children and adolescents of the same age group. Depending on MIH severity, the presence of early plaque-forming species and cariogenic biofilm may increase, requiring intensive, tailored preventive care and appropriate restorative treatment to achieve microbial homeostasis.<br><br>IMPORTANCE: Molar-incisor-hypomineralization (MIH) represents a significant burden for affected children and adolescents, playing an increasingly important role in pediatric dentistry worldwide. Despite its high global prevalence, data on the microbiome of MIH patients remains limited. This study is the first to compare the oral microbiome composition of MIH patients with a healthy control group, making a significant contribution to pediatric dentistry and microbiology. Our results indicate that the oral microbiome of children with MIH is similar to that of healthy children of the same age. Although this structural anomaly predisposes patients to caries, effective preventive and restorative treatments can help maintain microbial homeostasis. However, MIH-affected children remain high-risk patients, as the disease severity may reduce microbial diversity. Furthermore, the increased abundance of Streptococcus spp. in MIH patients indicates a higher caries susceptibility, emphasizing the need for targeted dental care focusing on plaque control and topical fluoride use.}, }
@article {pmid40161742, year = {2025}, author = {Wong, MK and Armstrong, E and Heirali, AA and Schneeberger, PHH and Chen, H and Cochrane, K and Sherriff, K and Allen-Vercoe, E and Siu, LL and Spreafico, A and Coburn, B}, title = {Assessment of ecological fidelity of human microbiome-associated mice in observational studies and an interventional trial.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2025.03.11.642547}, pmid = {40161742}, issn = {2692-8205}, abstract = {UNLABELLED: Composition and function of the gut microbiome is associated with diverse health conditions and treatment responses. Human microbiota-associated (HMA) mouse models are used to establish causal links for these associations but have important limitations. We assessed the fidelity of HMA mouse models to recapitulate ecological responses to a microbial consortium using stools collected from a human clinical trial. HMA mice were generated using different routes of consortium exposure and their ecological features were compared to human donors by metagenomic sequencing. HMA mice were more similar in gut composition to other mice than their respective human donors, with taxa including Akkermansia muciniphila and Bacteroides species enriched in mouse recipients. A limited repertoire of microbes was able to engraft into HMA mice regardless of route of consortium exposure. In publicly available HMA mouse datasets from four distinct health conditions, we confirmed our observation that a taxonomically restricted set of microbes reproducibly engrafts in HMA mice and observed that stool microbiome composition of HMA mice were more like other mice than their human donor. Our data suggest that HMA mice are limited models to assess the ecological impact of microbial consortia, with ecological effects in HMA mice being more strongly associated with host species than donor stool ecology or ecological responses to treatment in humans. Comparisons to published studies suggest this may be due to comparatively large host-species effects that overwhelm ecological effects of treatment in humans that HMA models aim to recapitulate.<br><br>IMPORTANCE: Human microbiota-associated (HMA) mice are models that better represent human gut ecology compared to conventional laboratory mice and are commonly used to test the effect of the gut microbiome on disease or treatment response. We evaluated the fidelity of using HMA mice as avatars of ecological response to a human microbial consortium, MET4. Our results show that HMA mice in our cohort and across other published studies are more similar to each other than the human donors or inoculum they are derived from and harbour a taxonomically restricted gut microbiome. These findings highlight the limitations of HMA mice in evaluating the ecological effects of complex human microbiome-targeting interventions, such as microbial consortia.}, }
@article {pmid40158322, year = {2025}, author = {Hamza, M and Wang, S and Liu, Y and Li, K and Zhu, M and Chen, L}, title = {Unraveling the potential of bioengineered microbiome-based strategies to enhance cancer immunotherapy.}, journal = {Microbiological research}, volume = {296}, number = {}, pages = {128156}, doi = {10.1016/j.micres.2025.128156}, pmid = {40158322}, issn = {1618-0623}, abstract = {The human microbiome plays a pivotal role in the field of cancer immunotherapy. The microbial communities that inhabit the gastrointestinal tract, as well as the bacterial populations within tumors, have been identified as key modulators of therapeutic outcomes, affecting immune responses and reprogramming the tumor microenvironment. Advances in synthetic biology have made it possible to reprogram and engineer these microorganisms to improve antitumor activity, enhance T-cell function, and enable targeted delivery of therapies to neoplasms. This review discusses the role of the microbiome in modulating both innate and adaptive immune mechanisms-ranging from the initiation of cytokine production and antigen presentation to the regulation of immune checkpoints-and discusses how these mechanisms improve the efficacy of immune checkpoint inhibitors. We highlight significant advances with bioengineered strains like Escherichia coli Nissle 1917, Lactococcus lactis, Bifidobacterium, and Bacteroides, which have shown promising antitumor efficacy in preclinical models. These engineered microorganisms not only efficiently colonize tumor tissues but also help overcome resistance to standard therapies by reprogramming the local immune environment. Nevertheless, several challenges remain, such as the requirement for genetic stability, effective tumor colonization, and the control of potential safety issues. In the future, the ongoing development of genetic engineering tools and the optimization of bacterial delivery systems are crucial for the translation of microbiome-based therapies into the clinic. This review highlights the potential of bioengineered microbiota as an innovative, personalized approach in cancer immunotherapy, bringing hope for more effective and personalized treatment options for patients with advanced malignancies.}, }
@article {pmid40158141, year = {2025}, author = {Jiang, Y and Aton, M and Zhu, Q and Lu, YY}, title = {Modeling microbiome-trait associations with taxonomy-adaptive neural networks.}, journal = {Microbiome}, volume = {13}, number = {1}, pages = {87}, pmid = {40158141}, issn = {2049-2618}, support = {RGPIN-03270-2023//Canadian NSERC Discovery Grant/ ; RGPIN-03270-2023//Canadian NSERC Discovery Grant/ ; }, mesh = {Humans ; *Neural Networks, Computer ; *Microbiota ; Metagenomics/methods ; Bacteria/classification/genetics ; Computer Simulation ; }, abstract = {The human microbiome, a complex ecosystem of microorganisms inhabiting the body, plays a critical role in human health. Investigating its association with host traits is essential for understanding its impact on various diseases. Although shotgun metagenomic sequencing technologies have produced vast amounts of microbiome data, analyzing such data is highly challenging due to its sparsity, noisiness, and high feature dimensionality. Here, we develop MIOSTONE, an accurate and interpretable neural network model for microbiome-disease association that simulates a real taxonomy by encoding the relationships among microbial features. The taxonomy-encoding architecture provides a natural bridge from variations in microbial taxa abundance to variations in traits, encompassing increasingly coarse scales from species to domains. MIOSTONE has the ability to determine whether taxa within the corresponding taxonomic group provide a better explanation in a data-driven manner. MIOSTONE serves as an effective predictive model, as it not only accurately predicts microbiome-trait associations across extensive simulated and real datasets but also offers interpretability for scientific discovery. Both attributes are crucial for facilitating in silico investigations into the biological mechanisms underlying such associations among microbial taxa. Video Abstract.}, }
@article {pmid40156096, year = {2025}, author = {Patjas, A and Kantele, A}, title = {Travel to low- and middle-income countries and travellers' diarrhoea increase risk of mismatching antimicrobial therapy for urinary tract infection.}, journal = {Journal of travel medicine}, volume = {}, number = {}, pages = {}, doi = {10.1093/jtm/taaf025}, pmid = {40156096}, issn = {1708-8305}, abstract = {BACKGROUND: Travel to low- and middle-income countries (LMICs) increases the risk of urinary tract infections (UTIs), including those caused by extended-spectrum beta-lactamase-producing Enterobacterales (ESBL-PE). Focusing on international travel, we explored resistance profiles of urinary ESBL-PE and non-ESBL-PE isolates in a low antimicrobial resistance prevalence country and factors associated with UTI treatment failure.<br><br>METHODS: During 2015-19, we recruited 18-65-year-old individuals with recent ESBL-PE UTI and a respective cohort of those with non-ESBL-PE UTI to complete questionnaires on symptoms, antibiotic therapies, and treatment failure risk factors. We compared uropathogens' resistance profiles among patients with or without LMIC travel history and conducted multivariable analyses to identify factors contributing to mismatching antimicrobial treatment (uropathogen resistant to the initial antimicrobial used) and clinical failure.<br><br>RESULTS: Among non-ESBL-PE UTI patients (n&#x2009;=&#x2009;187), trimethoprim resistance was more common in isolates from individuals with recent LMIC travel (8/19, 42.1%) compared to those without (30/167, 18.0%) (OR 3.3, CI95% 1.2-9.0). ESBL-PE isolates (n&#x2009;=&#x2009;130) showed no differences in resistance profiles with respect to LMIC travel history.In the group non-ESBL-PE UTI, risk factors included microbiological mismatching recent LMIC travel (AOR 3.6, CI95% 1.0-12.7) and travellers' diarrhoea (AOR 7.1, CI95% 1.1-45.6); no factors were significantly associated with mismatching in the group ESBL-PE UTI. As risk factors for clinical failure, in the group non-ESBL-PE UTI, we identified microbiological mismatching (AOR 15.2, CI95% 4.0-57.9), and renal/bladder disease (AOR 5.2, CI95% 1.1-23.2), and in the group ESBL-PE UTI, microbiological mismatching (AOR 8.1, CI95% 2.6-24.7).<br><br>CONCLUSIONS: LMIC travel increases the risk of nonmatching empiric antimicrobials, concurring with increased trimethoprim resistance rates among the non-ESBL-PE isolates. Our data suggest that UTI patients with recent LMIC travel should not be empirically treated with trimethoprim and, when possible, urinary culturing is warranted.}, }
@article {pmid40155374, year = {2025}, author = {Zhang, J and Zhang, D and Xu, Y and Zhang, J and Liu, R and Gao, Y and Shi, Y and Cai, P and Zhong, Z and He, B and Li, X and Zhou, H and Chen, M and Li, YX}, title = {Large-scale biosynthetic analysis of human microbiomes reveals diverse protective ribosomal peptides.}, journal = {Nature communications}, volume = {16}, number = {1}, pages = {3054}, pmid = {40155374}, issn = {2041-1723}, support = {C7014-24GF//Research Grants Council, University Grants Committee (RGC, UGC)/ ; }, mesh = {Humans ; Animals ; Mice ; *Gastrointestinal Microbiome ; *Peptides/metabolism/chemistry ; *Microbiota ; *Ribosomes/metabolism ; *Protein Processing, Post-Translational ; Biofilms ; Inflammatory Bowel Diseases/microbiology ; Biological Products/metabolism ; Genome, Bacterial ; Mice, Inbred C57BL ; Ribosomal Proteins/metabolism/genetics ; }, abstract = {The human microbiome produces diverse metabolites that influence host health, yet the chemical landscape of ribosomally synthesized and post-translationally modified peptides (RiPPs)-a versatile class of bioactive compounds-remains underexplored. Here, we conduct a large-scale biosynthetic analysis of 306,481 microbial genomes from human-associated microbiomes, uncovering a broad array of yet-to-be-discovered RiPPs. These RiPPs are distributed across various body sites but show a specific enrichment in the gut and oral microbiome. Big data omics analysis reveals that numerous RiPP families are inversely related to various diseases, suggesting their potential protective effects on health. For a proof of principle study, we apply the synthetic-bioinformatic natural product (syn-BNP) approach to RiPPs and chemically synthesize nine autoinducing peptides (AIPs) for in vitro and ex vivo assay. Our findings reveal that five AIPs effectively inhibit the biofilm formation of disease-associated pathogens. Furthermore, when ex vivo testing gut microbiota from mice with inflammatory bowel disease, we observe that two AIPs can regulate the microbial community and reduce harmful species. These findings highlight the vast potential of human microbial RiPPs in regulating microbial communities and maintaining human health, emphasizing their potential for therapeutic development.}, }
@article {pmid40144639, year = {2025}, author = {Sabu, P and Pathak, HB and Nissen, E and Chalise, P and Koestler, DC and Godwin, AK and Umar, S and Spoozak, L and Jewell, A and Mahoney, DE}, title = {Translational Implications of The Gut Microbiome in Women with A Benign or Malignant Pelvic Mass.}, journal = {Annals of obstetrics and gynecology}, volume = {8}, number = {1}, pages = {}, pmid = {40144639}, issn = {2641-6522}, abstract = {OBJECTIVE: The role of the gut microbiome in non-gastrointestinal cancers has generated growing interest in the field of gynecologic oncology. Our objective was to characterize the gut microbiome in women with a pelvic mass suspicious for ovarian cancer. We hypothesized that (1) women with a pelvic mass would have reduced gut microbiota bacterial diversity compared to healthy controls and (2) gut microbial diversity would differ between benign disease compared to ovarian cancer.<br><br>METHODS: In this case-control observational study, patients who presented with a suspicious pelvic mass were recruited from university affiliated gynecologic oncology clinics for fecal biospecimen donation. Fecal samples that were obtained from patients underwent 16S rRNA gene sequencing for microbial evaluation and statistical analysis. We used the Human Microbiome Project (HMP) Data Portal to compare gut microbiota profiles for our study to that of healthy female controls.<br><br>RESULTS: Fifteen patients with a pelvic mass were included ages 24-75 years. When comparing the gut microbiomes of these patients to 82 healthy females from the HMP Dataset, those with a pelvic mass had a significantly lower microbiota gut bacterial diversity. On the final pathology, 8 of the 15 patients with a suspicious pelvic mass had ovarian cancer and 7 had benign disease. Although not statistically significant, the alpha diversity was marginally reduced in patients with ovarian cancer compared to those with benign disease.<br><br>CONCLUSION: These findings underscore the necessity for validation in larger patient cohorts for clinical translation as a potential tool for disease diagnostics and disease prediction in diverse populations.}, }
@article {pmid40142442, year = {2025}, author = {Fan, X and Lv, N and Quan, Z}, title = {Culturable Human Microorganisms and the Impact of Transportation Conditions on Cultivability.}, journal = {Microorganisms}, volume = {13}, number = {3}, pages = {}, doi = {10.3390/microorganisms13030549}, pmid = {40142442}, issn = {2076-2607}, support = {2021YFA1301000//the National Key Research and Development Program of China/ ; 2017SHZDZX01//Shanghai Municipal Science and Technology Major Project/ ; 32470099//the National Natural Foundation of China/ ; }, abstract = {The composition of the human microbiome is a critical health indicator, and culture-independent methodologies have substantially advanced our understanding of human-associated microorganisms. However, precise identification and characterization of microbial strains require culture-based techniques. Recently, the resurgence of culturomics, combined with high-throughput sequencing technology, has reduced the high labor demand of pure culture methods, facilitating a more efficient and comprehensive acquisition of culturable microbial strains. This study employed an integrated approach combining culturomic and high-throughput sequencing to identify culturable microorganisms on the human scalp and in human saliva and feces. Several Staphylococcus strains were identified from the scalp, whereas anaerobic microorganisms were dominant in the saliva and fecal samples. Additionally, the study highlighted the beneficial effects of transportation conditions (liquid nitrogen treatment, dry ice transport, and dimethyl sulfoxide [DMSO] buffer) in preserving culturable microorganisms. A robust methodology was developed for the large-scale acquisition of culturable microorganisms with optimized transport conditions that enhance the potential for isolating a greater diversity of culturable strains.}, }
@article {pmid40140901, year = {2025}, author = {Wu, Y and Cheng, R and Lin, H and Li, L and Jia, Y and Philips, A and Zuo, T and Zhang, H}, title = {Gut virome and its implications in the pathogenesis and therapeutics of inflammatory bowel disease.}, journal = {BMC medicine}, volume = {23}, number = {1}, pages = {183}, pmid = {40140901}, issn = {1741-7015}, support = {2023YFS0279//Sichuan Science and Technology Program/ ; }, mesh = {Humans ; *Inflammatory Bowel Diseases/therapy/microbiology/virology ; *Virome ; *Gastrointestinal Microbiome ; }, abstract = {Inflammatory bowel disease (IBD) refers to chronic, recurrent inflammatory intestinal disorders, primarily including Crohn's disease (CD) and Ulcerative colitis (UC). Numerous studies have elucidated the importance of the gut microbiome in IBD. Recently, numerous studies have focused on the gut virome, an intriguing and enigmatic aspect of the gut microbiome. Alterations in the composition of phages, eukaryotic viruses, and human endogenous retroviruses that occur in IBD suggest potential involvement of the gut virome in IBD. Nevertheless, the mechanisms by which it maintains intestinal homeostasis and interacts with diseases are only beginning to be understood. Here, we thoroughly reviewed the composition of the gut virome in both healthy individuals and IBD patients, emphasizing the key viruses implicated in the onset and progression of IBD. Furthermore, the complex connections between the gut virome and the intestinal barrier, immunity, and gut microbiome were dissected to advance the interpretation of IBD pathogenesis. The updated discussion of the evidence regarding the gut virome will advance our knowledge in gut virome and chronic gastrointestinal diseases. Targeting the gut virome is a promising avenue for IBD treatment in future.}, }
@article {pmid40140341, year = {2025}, author = {Rodolfi, S and Selmi, C}, title = {Environmental factors and rheumatic diseases.}, journal = {Best practice &amp; research. Clinical rheumatology}, volume = {}, number = {}, pages = {102053}, doi = {10.1016/j.berh.2025.102053}, pmid = {40140341}, issn = {1532-1770}, abstract = {The pathogenesis and pathophysiology of rheumatic diseases is complex and relies on the interaction of different factors. The common view is that the pathological autoimmunity develops in genetically predisposed individuals upon exposure to an environmental trigger. This highlights the importance of recognizing and deconstructing the effects of environmental agents in rheumatic diseases. Several factors have been identified in the last decades, with detrimental or protective effects, impacting not only on disease onset, but also on its natural history. Cigarette smoking has been identified as one of the strongest environmental risk factors, being associated with disease development and severity for several rheumatic diseases, including rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and spondyloarthropathies. Moreover, other airborne pollutants, such as silica, solvents, asbestos and metals are recognized risk factors for rheumatic diseases. The effect of some other agents is however not straightforward, of which a remarkable example is alcohol consumption. Alcohol has been associated with both pro- and anti-inflammatory effects, exerting a variable effect on rheumatic diseases depending on quantity and frequency of consumption, as well as sex and ethnicity. Similarly, ultraviolet light exposure has been associated with a higher risk of SLE but lower risk of RA. The relationship between microbial exposure and autoimmunity is also complex: while some infectious agents increase the risk of rheumatic diseases, it is widely accepted that less exposure to microbial agents, particularly during immune system development, increases the risk of autoimmunity. Furthermore, in recent years the spotlight has switched to the human microbiome, as alterations in organ-specific microbiome composition are anticipated to be early participants in the onset of immune-mediated illnesses. The aim of this review is to highlight the most relevant environmental factors and their role in Rheumatology, with a specific focus on proposed pathophysiological effect and correlation with clinical outcomes.}, }
@article {pmid40137778, year = {2025}, author = {Papamentzelopoulou, M and Pitiriga, VC}, title = {Unlocking the Interactions Between the Whole-Body Microbiome and HPV Infection: A Literature Review.}, journal = {Pathogens (Basel, Switzerland)}, volume = {14}, number = {3}, pages = {}, doi = {10.3390/pathogens14030293}, pmid = {40137778}, issn = {2076-0817}, mesh = {Humans ; *Papillomavirus Infections/immunology/virology ; *Microbiota/physiology ; Female ; Papillomaviridae/genetics ; Uterine Cervical Neoplasms/virology/immunology/microbiology ; Dysbiosis/immunology ; }, abstract = {The human microbiome plays a vital role in maintaining human homeostasis, acting as a key regulator of host immunity and defense mechanisms. However, dysbiotic microbial communities may cause disruption of the symbiotic relationship between the host and the local microbiota, leading to the pathogenesis of various diseases, including viral infections and cancers. One of the most common infectious agents causing cancer is the human papilloma virus (HPV), which accounts for more than 90% of cervical cancers. In most cases, the host immune system is activated and clears HPV, whereas in some cases, the infection persists and can lead to precancerous lesions. Over the last two decades, the advent of next-generation sequencing (NGS) technology and bioinformatics has allowed a thorough and in-depth analysis of the microbial composition in various anatomical niches, allowing researchers to unveil the interactions and the underlying mechanisms through which the human microbiota could affect HPV infection establishment, persistence, and progression. Accordingly, the present narrative review aims to shed light on our understanding of the role of the human microbiome in the context of HPV infection and its progression, mainly to cervical cancer. Furthermore, we explore the mechanisms by which the composition and balance of microbial communities exert potential pathogenic or protective effects, leading to either HPV persistence and disease outcomes or clearance. Special interest is given to how the microbiome can modulate host immunity to HPV infection. Lastly, we summarize the latest findings on the therapeutic efficacy of probiotics and prebiotics in preventing and/or treating HPV infections and the potential of vaginal microbiota transplantation while highlighting the significance of personalized medicine approaches emerging from NGS-based microbiome profiling and artificial intelligence (AI) for the optimal management of HPV-related diseases.}, }
@article {pmid40137432, year = {2025}, author = {Ziogou, A and Giannakodimos, I and Giannakodimos, A and Mitakidi, E and Charalampakis, N and Ioannou, P}, title = {Primary Actinomycosis of the Stomach: A Review of the Literature for A Rare Entity.}, journal = {Journal of personalized medicine}, volume = {15}, number = {3}, pages = {}, doi = {10.3390/jpm15030116}, pmid = {40137432}, issn = {2075-4426}, abstract = {Background/Objectives: Primary gastric actinomycosis is extremely rare and only a limited number of cases are published in the literature. Actinomycosis is caused by anaerobic Gram-positive bacteria; these microorganisms are members of the normal human microbiome and occasionally lead to infection, especially in immunocompromised patients or patients subjected to abdominal surgery. Advances in personalized medicine, including tailored antimicrobial therapy based on individual patient profiles, may enhance treatment efficacy and reduce unnecessary interventions. Methods: A review was performed through a literature search of the PubMed/MedLine and Scopus databases. Results: A total of 27 patients were included, 15 males (55.56%) and 12 (44.44%) females, with a mean age of 55.11 ± 17.48 years. Among the included patients, 25.93% had a history of abdominal surgery. Abdominal pain (73.08%), weight loss (40.74%), nausea or vomiting (30.77%) and fever (19.23%) constitute the most commonly reported clinical manifestations. Endoscopy (59.26%), computed tomography (48.15%), ultrasonography (22.22%) and magnetic resonance imaging (11.11%) assisted in indicating the primary lesion. Diagnosis was achieved preoperatively in 66.66% of patients, via endoscopy and biopsy (51.85%) or via cultures (14.81%), while nine cases (33.33%) were diagnosed postoperatively. The therapeutic approaches included antimicrobial administration (32%), surgery (24%) or both (44%). The most widely used antimicrobial was penicillin (77.78%) and the mean duration of antimicrobial treatment was 5.85 months. The protocol for this review was registered in Prospero (ID:CRD42025649532). Conclusions: Due to the divergent clinical presentation of primary gastric actinomycosis, clinicians should be aware of this rare entity in order to establish diagnosis in a timely manner and provide prompt and effective treatment.}, }
@article {pmid40128848, year = {2025}, author = {Byrne, SR and DeMott, MS and Yuan, Y and Ghanegolmohammadi, F and Kaiser, S and Fox, JG and Alm, EJ and Dedon, PC}, title = {Temporal dynamics and metagenomics of phosphorothioate epigenomes in the human gut microbiome.}, journal = {Microbiome}, volume = {13}, number = {1}, pages = {81}, pmid = {40128848}, issn = {2049-2618}, support = {T32-ES007020//NIEHS Training Grant in Environmental Toxicology/ ; R01-OD028099-01//NIH Transformative Award/ ; R01-OD028099-01//NIH Transformative Award/ ; P30-ES002109//NIEHS Core Center Grant/ ; }, mesh = {Humans ; *Gastrointestinal Microbiome/genetics ; *Metagenomics/methods ; *Feces/microbiology ; *Bacteria/genetics/classification/metabolism ; Mice ; Animals ; Epigenesis, Genetic ; Epigenome ; Female ; Male ; Phosphates/metabolism ; }, abstract = {BACKGROUND: Epigenetic regulation of gene expression and host defense is well established in microbial communities, with dozens of DNA modifications comprising the epigenomes of prokaryotes and bacteriophage. Phosphorothioation (PT) of DNA, in which a chemically reactive sulfur atom replaces a non-bridging oxygen in the sugar-phosphate backbone, is catalyzed by dnd and ssp gene families widespread in bacteria and archaea. However, little is known about the role of PTs or other microbial epigenetic modifications in the human microbiome. Here we optimized and applied fecal DNA extraction, mass spectrometric, and metagenomics technologies to characterize the landscape and temporal dynamics of gut microbes possessing PT modifications.<br><br>RESULTS: Exploiting the nuclease-resistance of PTs, mass spectrometric analysis of limit digests of PT-containing DNA reveals PT dinucleotides as part of genomic consensus sequences, with 16 possible dinucleotide combinations. Analysis of mouse fecal DNA revealed a highly uniform spectrum of 11 PT dinucleotides in all littermates, with PTs estimated to occur in 5-10% of gut microbes. Though at similar levels, PT dinucleotides in fecal DNA from 11 healthy humans possessed signature combinations and levels of individual PTs. Comparison with a widely distributed microbial epigenetic mark, m[6]dA, suggested temporal dynamics consistent with expectations for gut microbial communities based on Taylor's Power Law. Application of PT-seq for site-specific metagenomic analysis of PT-containing bacteria in one fecal donor revealed the larger consensus sequences for the PT dinucleotides in Bacteroidota, Bacillota (formerly Firmicutes), Actinomycetota (formerly Actinobacteria), and Pseudomonadota (formerly Proteobacteria), which differed from unbiased metagenomics and suggested that the abundance of PT-containing bacteria did not simply mirror the spectrum of gut bacteria. PT-seq further revealed low abundance PT sites not detected as dinucleotides by mass spectrometry, attesting to the complementarity of the technologies. Video Abstract CONCLUSIONS: The results of our studies provide a benchmark for understanding the behavior of an abundant and chemically reactive epigenetic mark in the human gut microbiome, with implications for inflammatory conditions of the gut.}, }
@article {pmid40122597, year = {2025}, author = {Su, R and Wen, W and Jin, Y and Cao, Z and Feng, Z and Chen, J and Lu, Y and Zhou, G and Dong, C and Gao, S and Li, X and Zhang, H and Chao, K and Lan, P and Wu, X and Philips, A and Li, K and Gao, X and Zhang, F and Zuo, T}, title = {Dietary whey protein protects against Crohn's disease by orchestrating cross-kingdom interaction between the gut phageome and bacteriome.}, journal = {Gut}, volume = {}, number = {}, pages = {}, doi = {10.1136/gutjnl-2024-334516}, pmid = {40122597}, issn = {1468-3288}, abstract = {BACKGROUND: The gut microbiome and diet are important factors in the pathogenesis and management of Crohn's disease (CD). However, the role of the gut phageome under dietary influences is unknown.<br><br>OBJECTIVE: We aim to explore the effect of diet on the gut phageome-bacteriome interaction linking to CD protection.<br><br>DESIGN: We recruited CD patients and healthy subjects (n=140) and conducted a multiomics investigation, including paired ileal mucosa phageome and bacteriome profiling, dietary survey and phenome interrogation. We screened for the effect of diet on the gut phageome and bacteriome, as well as its epidemiological association with CD risks. The underlying mechanisms were explored in target phage-bacteria monocultures and cocultures in vitro and in two mouse models in vivo.<br><br>RESULTS: On dietary screening in humans, whey protein (WP) consumption was found to profoundly impact the gut phageome and bacteriome (more pronounced on the phageome) and was associated with a lower CD risk. Indeed, the WP reshaped gut phageome can causally attenuate intestinal inflammation, as shown by faecal phageome versus bacteriome transplantation from WP-consuming versus WP-non-consuming mice to recipient mice. Mechanistically, WP induced phage (a newly isolated phage AkkZT003P herein) lysis of the mucin-foraging bacterium Akkermansia muciniphila, which unleashed the symbiotic bacterium Streptococcus thermophilus to counteract intestinal inflammation.<br><br>CONCLUSION: Our study charted the importance of cross-kingdom interaction between gut phage and bacteria in mediating the dietary effect on CD protection. Importantly, we uncovered a beneficial dietary WP, a keystone phage AkkZT003P, and a probiotic S. thermophilus that can be used in CD management in the future.}, }
@article {pmid40120775, year = {2025}, author = {Onali, T and Slabá, H and Jian, C and Koivumäki, T and Päivärinta, E and Marttinen, M and Määttänen, M and Salonen, A and Pajari, AM}, title = {Berry supplementation in healthy volunteers modulates gut microbiota, increases fecal polyphenol metabolites and reduces viability of colon cancer cells exposed to fecal water- a randomized controlled trial.}, journal = {The Journal of nutritional biochemistry}, volume = {}, number = {}, pages = {109906}, doi = {10.1016/j.jnutbio.2025.109906}, pmid = {40120775}, issn = {1873-4847}, abstract = {SCOPE: Diets high in red and processed meat and low in plant-based foods are associated with an increased risk of colorectal cancer. We investigated whether berry supplementation can impact gut metabolism to counteract the presumably cancer promoting luminal environment sustained by high red and processed meat consumption.<br><br>METHODS AND RESULTS: Altogether 43 healthy adults were randomized either into Meat group (150 g/d red and processed pork meat) or Meat &amp; Berries group (150 g/d red and processed meat and 200 g/d of mixed berries). Fecal samples and 3-day food records were collected at baseline and at the end of the four-week intervention. Intakes of vitamin C, vitamin E, manganese, insoluble fibre, and the polyphenols available in the database were significantly higher in the Meat &amp; Berries than Meat group. While between-group comparisons found no significant differences in the gut microbiota, the within-group analyses showed that the relative abundances of beneficial Roseburia and Faecalibacterium were decreased and an unclassified group of Peptostreptococcaceae increased significantly in the Meat group. In comparison to the Meat group, berry consumption resulted in higher fecal concentrations of p-coumaric and protocatechuic acids and lower viability of fecal water (FW) -treated CV1-P fibroblastoma and human colon adenocarcinoma HCA-7 and Caco-2 cells (P<0.05 with 30% FW).<br><br>CONCLUSIONS: Berry consumption provided protective nutrients and mitigated potentially unfavourable gut microbiota changes seen in the Meat group, increased fecal polyphenol metabolites, and reduced viability of FW-treated colon adenocarcinoma cells, collectively suggesting that berries may protect against colorectal cancer development.}, }
@article {pmid40120687, year = {2025}, author = {Caffrey, EB and Perelman, D and Ward, CP and Sonnenburg, ED and Gardner, CD and Sonnenburg, JL}, title = {Unpacking food fermentation: Clinically relevant tools for fermented food identification and consumption.}, journal = {Advances in nutrition (Bethesda, Md.)}, volume = {}, number = {}, pages = {100412}, doi = {10.1016/j.advnut.2025.100412}, pmid = {40120687}, issn = {2156-5376}, abstract = {Fermented foods have been consumed for millennia, valued for their extended shelf life, distinctive sensory properties, and potential health benefits. Emerging research suggests that fermented food consumption may contribute to gut microbiome diversity, immune modulation, and metabolic regulation; however, mechanistic insights and clinical validation remain limited. This review synthesizes current scientific evidence on the microbial and metabolite composition of fermented foods, their proposed health effects, and safety considerations for vulnerable populations. Additionally, we highlight the need for standardized definitions, serving sizes, and regulatory frameworks to enhance consumer transparency and research reproducibility. By providing a structured overview of existing data and knowledge gaps, this review establishes a foundation for integrating fermented foods into dietary recommendations and guiding future research directions. STATEMENT OF SIGNIFICANCE: While fermented foods have demonstrated benefits to human health, the gap between scientific research and marketing claims, including lack of regulatory standards in labeling can be disorienting to consumers seeking these potential benefits. This review provides an updated perspective on the role of fermented foods in health, emphasizing clinically relevant tools, research opportunities, and labeling recommendations to guide their identification and use.}, }
@article {pmid40119445, year = {2025}, author = {Niaz, H and Skurnik, M and Adnan, F}, title = {Genomic and proteomic characterization of four novel Schitoviridae family phages targeting uropathogenic Escherichia coli strain.}, journal = {Virology journal}, volume = {22}, number = {1}, pages = {83}, pmid = {40119445}, issn = {1743-422X}, mesh = {Humans ; *Genome, Viral ; *Uropathogenic Escherichia coli/virology/genetics ; *Host Specificity ; *Phylogeny ; *Proteomics ; Genomics ; Phage Therapy ; Urinary Tract Infections/microbiology/virology ; Escherichia coli Infections/microbiology ; Coliphages/genetics/isolation &amp; purification/ultrastructure/classification/physiology ; Wastewater/virology/microbiology ; Proteome ; Bacteriophages/genetics/isolation &amp; purification/classification/ultrastructure/physiology ; }, abstract = {BACKGROUND: Escherichia coli-associated urinary tract infections (UTIs) are among the most prevalent bacterial infections in humans. Typically, antibiotic medication is used to treat UTIs, but over the time, growth of multidrug resistance among these bacteria has created a global public health issue that necessitates other treatment modalities, such as phage therapy.<br><br>METHODS: The UPEC strain PSU-5266 (UE-17) was isolated from human urine samples, while phages were obtained from wastewater. These phages were characterized through host range analysis, stability studies, adsorption assays, and electron microscopy. Additionally, genomic, phylogenetic, and proteomic analyses were conducted to provide further insights.<br><br>RESULTS: The current study describes the isolation and characterization of four Escherichia coli phages designated as UE-S5a, UE-S5b, UE-M3 and UE-M6. Bactericidal assays depicted that all bacteriophages exhibited a strong lytic ability against uropathogenic E. coli (UPEC) strain PSU-5266 (UE-17). The phages displayed a broad host range (31-41%) among 104 tested isolates and adsorption rate of 15-20&#xa0;min. They were stable within pH range of 5-11 and temperature range of 4 to 55&#xa0;&#xb0;C. Electron microscopy showed that all phages have icosahedral heads (70-74&#xa0;nm) and short non-contractile tails, thus exhibiting a podovirus morphology. Sequencing results showed that they have linear double stranded DNA, genome of 73 to 76&#xa0;kb in length, with GC content of 42% and short direct terminal repeats. Their genomes contain 84-88 predicted genes with putative functions predicted to 42-48% of gene products. The phylogenetic and comparative genomic analysis results depicted that these phages, sharing&#x2009;>&#x2009;98% sequence similarity, are new members of genus Gamaleyavirus of subfamily Enquatrovirinae, in the Schitoviridae family. Mass spectrometric analysis of purified phage particles identified 44-56 phage particle-associated proteins (PPAPs) belonging to various functional groups such as lysis proteins, structural proteins, DNA packaging related proteins, and proteins involved in replication, metabolism and regulation. In addition, no genes encoding virulence factors, antibiotic resistance or lysogeny factors were identified.<br><br>CONCLUSION: The overall findings suggest that these bacteriophages are potential candidates for phage therapy in treating UTIs caused by UPEC strains.}, }
@article {pmid40119155, year = {2025}, author = {Heidrich, V and Valles-Colomer, M and Segata, N}, title = {Human microbiome acquisition and transmission.}, journal = {Nature reviews. Microbiology}, volume = {}, number = {}, pages = {}, pmid = {40119155}, issn = {1740-1534}, abstract = {As humans, we host personal microbiomes intricately connected to our biology and health. Far from being isolated entities, our microbiomes are dynamically shaped by microbial exchange with the surroundings, in lifelong microbiome acquisition and transmission processes. In this Review, we explore recent studies on how our microbiomes are transmitted, beginning at birth and during interactions with other humans and the environment. We also describe the key methodological aspects of transmission inference, based on the uniqueness of the building blocks of the microbiome - single microbial strains. A better understanding of human microbiome transmission will have implications for studies of microbial host regulation, of microbiome-associated diseases, and for effective microbiome-targeting strategies. Besides exchanging strains with other humans, there is also preliminary evidence we acquire microorganisms from animals and food, and thus a complete understanding of microbiome acquisition and transmission can only be attained by adopting a One Health perspective.}, }
@article {pmid40116497, year = {2025}, author = {Moreland, RB and Choi, BI and Fontes Noronha, M and Baker, J and Kaindl, J and Wolfe, AJ}, title = {Complete genome sequence of Trueperella bernardiae strain UMB8254, isolated from the bladder of a female with metabolic syndrome and nephrolithiasis.}, journal = {Microbiology resource announcements}, volume = {}, number = {}, pages = {e0126524}, doi = {10.1128/mra.01265-24}, pmid = {40116497}, issn = {2576-098X}, abstract = {Trueperella bernardiae is infrequently isolated, usually in polymicrobial communities, from human hosts with a wide variety of symptoms and diseases. Here, we report a complete genome sequence of Trueperella bernardiae (UMB8254), isolated from the bladder of a human female with metabolic syndrome and nephrolithiasis.}, }
@article {pmid40111698, year = {2025}, author = {Vernon, JJ}, title = {Modulation of the Human Microbiome: Probiotics, Prebiotics, and Microbial Transplants.}, journal = {Advances in experimental medicine and biology}, volume = {1472}, number = {}, pages = {277-294}, pmid = {40111698}, issn = {0065-2598}, mesh = {Humans ; *Prebiotics/administration &amp; dosage ; *Probiotics/therapeutic use ; *Microbiota/physiology ; Mouth/microbiology ; Gastrointestinal Microbiome/physiology ; Fecal Microbiota Transplantation/methods ; }, abstract = {The balance between health and disease is intrinsically linked to the interactions between microbial communities and the host. This complex environment of antagonism and synergy involves both prokaryotic and eukaryotic cells, whose collaborative metabolic pathways and immunomodulatory elements influence system homeostasis. As with the gut and other niches, the oral microbiome has the capacity to affect distal host sites. The ability to manipulate this environment holds the potential to impact local and systemic disease.With the increasing threat of antimicrobial resistance, novel approaches to reduce the burden of disease are essential. The use of probiotics and prebiotics is one such strategy. Probiotics introduce non-pathogenic bacteria into the environment to compete with pathogens for nutrients and attachment sites, or to produce metabolites that counteract disease aetiologies. Prebiotic compounds enhance the growth of health-associated organisms, offering additional benefits, whilst a conjunctive approach with probiotics potentially holds even greater promise. Though widely studied in the gastrointestinal context, their potential for treating oral diseases, such as dental caries and periodontitis, is less understood. Additionally, the use of microbial transplantations has demonstrated efficacy in other areas, reducing systemic inflammation and recolonising with commensal bacteria. Here we evaluate their use in the oral context and their modulatory impact on overall health.In this chapter, we discuss how pro- and prebiotic strategies seek to modulate both the oral and gut environments to promote oral health and prevent disease. We assess novel approaches for utilising health-associated microorganisms to combat oral disorders, either administered locally in the mouth or imparting influence through immune modulation via the oral-gut axis. By examining available clinical trial data, we aim to further understand the intricacies involved in this discipline. Furthermore, we consider the challenges facing the research community, including optimal candidate organism/compound selection and colonisation retention, as well as considerations for future research.}, }
@article {pmid40111686, year = {2025}, author = {Colombo, APV and Lourenço, TGB and de Oliveira, AM and da Costa, ALA}, title = {Link Between Oral and Gut Microbiomes: The Oral-Gut Axis.}, journal = {Advances in experimental medicine and biology}, volume = {1472}, number = {}, pages = {71-87}, pmid = {40111686}, issn = {0065-2598}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Mouth/microbiology ; *Dysbiosis/microbiology ; Animals ; Gastrointestinal Tract/microbiology ; }, abstract = {In the last decades, groundbreaking research on the human microbiome has changed our reductionist conception of the etiology and pathogenesis of several chronic diseases. As a result, we have come to appreciate the significance of a balanced microbiome in maintaining human health. In this context, the upper and lower gastrointestinal tracts (GITs) comprise the most abundant and diverse microbiotas of the human body. In addition to its diversity, functional redundancy, and temporal stability, a healthy GIT microbiome is characterized by its body site specificity. In fact, current evidence has indicated that the translocation of oral species to the gut environment through the oral-gut axis is increased in an array of illnesses, including chronic inflammatory and metabolic diseases, neurological disorders, and cancer. Oral pathogens have also been shown to promote gut dysbiosis and systemic inflammation in animal models. Yet, some level of overlapping between oral and gut microbiomes may occur without disruption of these microbial communities and loss of site specificity. The uniqueness of each host-microbiome entity may hinder our ability to define a "universal" normal GIT microbiome. Despite that, this chapter summarizes the predominant health-related taxa along the human GIT, as well as their role in the physiology and immunity of the digestive system. Some mechanisms that may lead to disturbances and relevant shifts in the oral and gut microbiomes of major inflammatory chronic diseases are also pointed out. Lastly, oral-fecal microbial signatures are presented as potential biomarkers for several oral and systemic disorders. The recognition of such symbiotic/dysbiotic microbial profiles may provide insights into the development of more accurate early diagnosis and therapeutic ecological approaches to restore the balance of the GIT microbiome.}, }
@article {pmid40111682, year = {2025}, author = {Dame-Teixeira, N and Do, T and Deng, D}, title = {The Oral Microbiome and Us.}, journal = {Advances in experimental medicine and biology}, volume = {1472}, number = {}, pages = {3-9}, pmid = {40111682}, issn = {0065-2598}, mesh = {Humans ; *Mouth/microbiology ; *Microbiota/physiology ; *Dysbiosis/microbiology ; Periodontitis/microbiology ; Animals ; Oral Health ; }, abstract = {Oral and systemic human health depend on the symbiotic relationship between the human host and its microbiome. As the second most diverse site of the human microbiome, the oral cavity is instrumental in symbiotic relationships, transforming nutrients and acting as the human body's initial barrier against pathogens. However, under certain conditions, the typically beneficial oral microbiome can become harmful. Systemic inflammatory diseases can send signals through the oral-gut axis, such as cytokines and host defensins, altering gene expression and, consequently, the composition of the oral microbiome. These changes can be responsible for causing oral diseases, such as periodontitis and candidiasis. Evidence of metabolic syndrome, including obesity, hypertension, hyperglycemia, and dyslipidemia, exacerbates oral microbiome dysbiosis. On the other hand, the oral microbiota can also influence systemic health. Inflammatory processes in the gingival structures caused by a dysbiotic oral microbiome are linked to worsen glycemic levels in diabetics, premature birth, and rheumatoid arthritis, among others. The idea for this book emerged from the need to explore the multifaceted nature of this relationship in its various dimensions. We discuss multispecies characteristics from an ecological perspective, focusing on how the host affects the microbiome and vice versa. Understanding how the oral microbiome influences human health will guide tailored strategies for disease prevention and treatment, which is discussed in the last section of the book. Looking ahead, predictive health and disease models will enable personalized therapies centered on restoring the healthy human microbiome.}, }
@article {pmid40111647, year = {2025}, author = {Choi, Y and Jeong, J and Kim, M and Cha, S and Han, K}, title = {Backtracking identification techniques for predicting unclear bacterial taxonomy at species level: molecular diagnosis-based bacterial classification.}, journal = {Genes &amp; genomics}, volume = {}, number = {}, pages = {}, pmid = {40111647}, issn = {2092-9293}, support = {RS-2024-00355393//National Institute for International Education/ ; }, abstract = {Bacterial 16S rRNA genes are widely used to classify bacterial communities within interesting environments (e.g., plants, water, human body) because they contain nine hyper-variable regions (V1-V9) reflecting a large number of sequence variation sites between species. Short-read sequencing platform (targeting partial region of 16S rRNA gene; approximately 150-500 bp) commonly used in the 16S-based microbiome study is favored by many researchers because it is economical and can generate highthroughput sequencing data faster than long-read sequencing platforms. However, this sequencing platform has technical limitations in that it cannot clarify bacterial classification at the species level compared to long-read sequencing technology, which can cover the unclassification issue due to sequence similarity between species by targeting the 16S full-length region. In recent microbiome research-related industries, species-level high-resolution microbial classification is considered a key challenge to secure microbial resources among institutions in the field. However, the long-read sequencing platforms currently offered are still under price adjustment (demanding higher cost than short-read sequencing platforms) and have the disadvantage of low base-calling accuracy compared to short-read sequencing platforms. Therefore, this brief communication introduces the'Molecular diagnosis-based bacterial classification' technology to predict candidate species by backtracking for unclassified bacterial taxonomy at the species level in the NGS-based 16S microbiome study.}, }
@article {pmid40110560, year = {2025}, author = {Adachi, A and Zhang, F and Kanaya, S and Ono, N}, title = {Quantifying uncertainty in microbiome-based prediction using Gaussian processes with microbial community dissimilarities.}, journal = {Bioinformatics advances}, volume = {5}, number = {1}, pages = {vbaf045}, pmid = {40110560}, issn = {2635-0041}, abstract = {SUMMARY: The human microbiome is closely associated with the health and disease of the human host. Machine learning models have recently utilized the human microbiome to predict health conditions and disease status. Quantifying predictive uncertainty is essential for the reliable application of these microbiome-based prediction models in clinical settings. However, uncertainty quantification in such prediction models remains unexplored. In this study, we have developed a probabilistic prediction model using a Gaussian process (GP) with a kernel function that incorporates microbial community dissimilarities. We evaluated the performance of probabilistic prediction across three regression tasks: chronological age, body mass index, and disease severity, using publicly available human gut microbiome datasets. The results demonstrated that our model outperformed existing methods in terms of probabilistic prediction accuracy. Furthermore, we found that the confidence levels closely matched the empirical coverage and that data points predicted with lower uncertainty corresponded to lower prediction errors. These findings suggest that GP regression models incorporating community dissimilarities effectively capture the characteristics of phylogenetic, high-dimensional, and sparse microbial abundance data. Our study provides a more reliable framework for microbiome-based prediction, potentially advancing the application of microbiome data in health monitoring and disease diagnosis in clinical settings.<br><br>The code is available at https://github.com/asahiadachi/gp4microbiome.}, }
@article {pmid39854218, year = {2025}, author = {Zeng, T and Sun, K and Mai, L and Hong, X and He, X and Lin, W and Chen, S and Yan, L}, title = {Extracellular Vesicle-Associated miR-ERIA Exerts the Antiangiogenic Effect of Macrophages in Diabetic Wound Healing.}, journal = {Diabetes}, volume = {74}, number = {4}, pages = {596-610}, doi = {10.2337/db24-0701}, pmid = {39854218}, issn = {1939-327X}, support = {82222014//The National Natural Science Foundation of China Excellent Young Scientists Fund/ ; 2023A03J0706//Ministry of Education, China; Guangzhou Science and Technology Program/ ; 2020B1111170009//Guangdong Clinical Research Center for Metabolic Diseases/ ; 202102100004//Guangzhou Key Laboratory for Metabolic Diseases/ ; 32271185//The National Natural Science Foundation of China/ ; Sun Yat-sen University//Key Laboratory of Human Microbiome and Chronic Diseases/ ; 82200902//National Natural Science Foundation of China/ ; }, mesh = {*Wound Healing/drug effects/physiology ; *Extracellular Vesicles/metabolism ; *MicroRNAs/metabolism/genetics ; *Macrophages/metabolism/drug effects ; Animals ; Humans ; Mice ; Glycation End Products, Advanced/metabolism ; Cell Movement/drug effects ; Human Umbilical Vein Endothelial Cells/metabolism ; Endothelial Cells/metabolism/drug effects ; Angiogenesis Inhibitors/pharmacology/therapeutic use ; Skin Ulcer/metabolism/genetics ; Diabetes Mellitus, Experimental/metabolism ; }, abstract = {An understanding of cell interactions is needed to identify therapeutic targets for diabetic cutaneous ulcers. We explored extracellular vesicles after treatment with advanced glycation end products (AGEs-EVs) derived from macrophages that can suppress diabetic cutaneous wound healing. We found that a novel miRNA enriched in AGEs-EVs (miR-ERIA) suppresses the migration and tube formation of vascular endothelial cells by targeting helicase with zinc finger 2. miR-ERIA offers a potential therapeutic target for diabetic cutaneous ulcers.}, }
@article {pmid40102379, year = {2025}, author = {Deng, L and Taelman, S and Olm, MR and Toe, LC and Balini, E and Ouédraogo, LO and Bastos-Moreira, Y and Argaw, A and Tesfamariam, K and Sonnenburg, ED and Hanley-Cook, GT and Ouédraogo, M and Ganaba, R and Van Criekinge, W and Huybregts, L and Stock, M and Kolsteren, P and Sonnenburg, JL and Lachat, C and Dailey-Chwalibóg, T}, title = {Maternal balanced energy-protein supplementation reshapes the maternal gut microbiome and enhances carbohydrate metabolism in infants: a randomized controlled trial.}, journal = {Nature communications}, volume = {16}, number = {1}, pages = {2683}, pmid = {40102379}, issn = {2041-1723}, support = {OPP1175213//Bill and Melinda Gates Foundation (Bill &amp; Melinda Gates Foundation)/ ; }, mesh = {Humans ; *Gastrointestinal Microbiome/drug effects ; Female ; *Dietary Supplements ; Infant ; Pregnancy ; Adult ; Burkina Faso ; *Carbohydrate Metabolism ; Infant, Newborn ; Feces/microbiology ; Dietary Proteins/metabolism ; Male ; Lactation ; }, abstract = {Balanced energy-protein (BEP) supplementation during pregnancy and lactation can improve birth outcomes and infant growth, with the gut microbiome as a potential mediator. The MISAME-III randomized controlled trial (ClinicalTrial.gov: NCT03533712) assessed the effect of BEP supplementation, provided during pregnancy and the first six months of lactation, on small-for-gestational age prevalence and length-for-age Z-scores at six months in rural Burkina Faso. Nested within MISAME-III, this sub-study examines the impact of BEP supplementation on maternal and infant gut microbiomes and their mediating role in birth outcomes and infant growth. A total of 152 mother-infant dyads (n = 71 intervention, n = 81 control) were included for metagenomic sequencing, with stool samples collected at the second and third trimesters, and at 1-2 and 5-6 months postpartum. BEP supplementation significantly altered maternal gut microbiome diversity, composition, and function, particularly those with immune-modulatory properties. Pathways linked to lipopolysaccharide biosynthesis were depleted and the species Bacteroides fragilis was enriched in BEP-supplemented mothers. Maternal BEP supplementation also accelerated infant microbiome changes and enhanced carbohydrate metabolism. Causal mediation analyses identified specific taxa mediating the effect of BEP on birth outcomes and infant growth. These findings suggest that maternal supplementation modulates gut microbiome composition and influences early-life development in resource-limited settings.}, }
@article {pmid40099907, year = {2025}, author = {Reetz, L and Schulze, L and Kronenberger, T and Selim, KA and Schaefle, T and Dema, T and Zipperer, A and Mößner, J and Poso, A and Grond, S and Peschel, A and Krismer, B}, title = {The human microbiome-derived antimicrobial lugdunin self-regulates its biosynthesis by a feed-forward mechanism.}, journal = {mBio}, volume = {}, number = {}, pages = {e0357124}, doi = {10.1128/mbio.03571-24}, pmid = {40099907}, issn = {2150-7511}, abstract = {Many human microbiome members inhibit bacterial competitors by production of antimicrobial compounds whose expression needs to be tightly controlled to balance the costs and benefits of compound biosynthesis. The nasal commensal Staphylococcus lugdunensis outcompetes Staphylococcus aureus using the antimicrobial lugdunin. The lugdunin biosynthetic gene cluster (BGC) encodes two potential regulators whose roles have remained unknown. Deletion of the regulator genes lugR or lugJ led to increased lugdunin production and/or immunity. While LugR was found to repress the transcription of the biosynthetic lugRABCTDZ operon, LugJ repressed the lugIEFGH export and immunity genes. Both regulators bound to different inverted repeats in the controlled promoter regions. Notably, both repressors were released from cognate promoters to allow transcription upon addition of exogenous lugdunin. Even minor structural changes disabled lugdunin derivatives to induce expression of its BGC, which is consistent with inferior binding to the predicted LugR and LugJ binding pockets. Thus, lugdunin controls its own biosynthesis through a feed-forward mechanism probably to avoid futile production.IMPORTANCEBiosynthetic gene clusters (BGCs) are usually tightly controlled to avoid production of costly goods at inappropriate time points or unfavorable conditions. However, in most cases, the regulatory signals of these clusters have remained unknown. Frequently, quorum sensing or two-component regulatory systems are involved in BGC expression control. This study elucidates the sophisticated regulation of lugdunin biosynthesis and secretion via two independent regulators, LugR and LugJ. Although belonging to different families of repressors, both directly interact with the antimicrobial lugdunin and thereby enhance biosynthesis and secretion in a feed forward-like mechanism.}, }
@article {pmid40086654, year = {2025}, author = {Pietilä, JP and Häkkinen, T and Ollgren, J and Kantele, A}, title = {Modelling international travel as risk of acquiring Dientamoeba fragilis: comparison to Giardia duodenalis data.}, journal = {Travel medicine and infectious disease}, volume = {}, number = {}, pages = {102836}, doi = {10.1016/j.tmaid.2025.102836}, pmid = {40086654}, issn = {1873-0442}, abstract = {BACKGROUND: The intestinal parasite Dientamoeba fragilis (DF) is spread worldwide and can cause prolonged gastrointestinal symptoms, yet its link to international travel has been scarcely studied. To explore this connection, we examined the association between DF cases and international travel history by destination, comparing the findings to data on Giardia duodenalis (GD), a common travel-acquired intestinal parasite.<br><br>METHODS: We analysed clinical data from patients with DF or GD infection in the Helsinki Metropolitan Area, categorizing the patients as travellers and non-travellers on the basis of their travel history. To assess acquisition risk by destination, we devised a DF/GD risk score (RS) relating case numbers to travel volumes as denominators in each destination, with travel data retrieved from the Official Statistics of Finland (OSF).<br><br>RESULTS: Travel history was reported less frequently by patients with DF (30%) than GD (60%). DF had the highest RSs for Africa (41.3), followed by Asia and Oceania (17.9) and the Americas (11.5). The respective GD RSs were 32.8, 25.4, and 11.9. The lowest RSs for both parasites were recorded for Eastern and Western Europe, Russia and the Baltic countries, and Scandinavia. For Asia and Oceania, the GD RS exceeded that of DF; for the other sites, DF had higher RSs than GD.<br><br>CONCLUSIONS: Dientamoeba fragilis appears to be transmitted both domestically and internationally. Although the overall acquisition risk appears low, for both Dientamoeba fragilis and Giardia duodenalis, the highest RSs are linked to visits to (sub)tropical regions, with subregional differences between the two parasites.}, }
@article {pmid40084887, year = {2025}, author = {Sun, Y-Y and Liu, N-N}, title = {Mycobiome: an underexplored kingdom in cancer.}, journal = {Microbiology and molecular biology reviews : MMBR}, volume = {}, number = {}, pages = {e0026124}, doi = {10.1128/mmbr.00261-24}, pmid = {40084887}, issn = {1098-5557}, abstract = {SUMMARYThe human microbiome, including bacteria, fungi, archaea, and viruses, is intimately linked to both health and disease. The relationship between bacteria and disease has received much attention and intensive investigation, while that of the fungal microbiome, also known as mycobiome, has lagged far behind bacteria. There is growing evidence showing mycobiome dysbiosis in cancer patients, and certain cancer-specific fungi may contribute to cancer progression by interacting with both host and bacteria. It was also demonstrated that the role of fungi-derived products in cancer should also not be underestimated. Therefore, investigating how fungal pathogenesis contributes to the onset and spread of cancer would yield crucial information for cancer diagnosis, prevention, and anti-cancer therapy.}, }
@article {pmid40084234, year = {2019}, author = {Werlang, C and Cárcarmo-Oyarce, G and Ribbeck, K}, title = {Engineering mucus to study and influence the microbiome.}, journal = {Nature reviews. Materials}, volume = {4}, number = {2}, pages = {134-145}, pmid = {40084234}, issn = {2058-8437}, abstract = {Mucus is a 3D hydrogel that houses the majority of the human microbiome. The mucous environment plays an important role in the differentiation and behaviour of microbial phenotypes and enables the creation of spatial distributions. Dysregulation of mucus is further associated with various diseases. Therefore, mucus is the key ingredient to study the behaviour of commensal and pathogenic microbiota in vitro. Indeed, microorganisms cultured in mucus exhibit phenotypes substantially different from those exhibited in standard laboratory media. In this Review, we discuss the impact of mucus on the microbiome and examine the structure and glycosylation of mucins - the main building blocks of mucus. We investigate the impact of glycans on mucin function and highlight different approaches for the engineering of synthetic mucins, including synthesis of the backbone, the design of mucin-mimetic hydrogels and the engineering of glycans. Finally, mucin mimetics for 3D in vitro cell culture and for modulating microbial community structure and function are discussed.}, }
@article {pmid40077792, year = {2025}, author = {Costa, CJ and Prescott, S and Fourie, NH and Abey, SK and Sherwin, LB and Rahim-Williams, B and Joseph, PV and Posada-Quintero, H and Hoffman, RK and Henderson, WA}, title = {Host Transcriptome and Microbial Variation in Relation to Visceral Hyperalgesia.}, journal = {Nutrients}, volume = {17}, number = {5}, pages = {}, doi = {10.3390/nu17050921}, pmid = {40077792}, issn = {2072-6643}, support = {1ZIANR000018-01-09; K22MD006143-01/GF/NIH HHS/United States ; }, mesh = {Humans ; *Hyperalgesia/microbiology ; *Transcriptome ; Male ; Female ; Adult ; Visceral Pain/microbiology ; Microbiota ; RNA, Messenger/metabolism ; Middle Aged ; Mouth/microbiology ; Gastrointestinal Microbiome ; Bacteria/genetics/classification ; Young Adult ; }, abstract = {BACKGROUND: Chronic visceral hypersensitivity is associated with an overstressed pain response to noxious stimuli (hyperalgesia). Microbiota are active modulators of host biology and are implicated in the etiology of visceral hypersensitivity.<br><br>OBJECTIVES: we studied the association between the circulating mRNA transcriptome, the intensity of induced visceral pain (IVP), and variation in the oral microbiome among participants with and without baseline visceral hypersensitivity.<br><br>METHODS: Transcriptomic profiles and microbial abundance were correlated with IVP intensity. Host mRNA and microbes associated with IVP were explored, linking variation in the microbiome to host RNA biology.<br><br>RESULTS: 259 OTUs were found to be associated with IVP through correlation to differential expression of 471 genes in molecular pathways related to inflammation and neural mechanisms, including Rho and PI3K/AKT pathways. The bacterial families Lachnospiraceae, Prevotellaceae, and Veillonellaceae showed the highest degree of association. Oral microbial profiles with reduced diversity were characteristic of participants with visceral hypersensitivity.<br><br>CONCLUSIONS: Our results suggest that the oral microbiome may be involved in systemic immune and inflammatory effects and play a role in nervous system and stem cell pathways. The interactions between visceral hypersensitivity, differentially expressed molecular pathways, and microbiota described here provide a framework for further work exploring the relationship between host and microbiome.}, }
@article {pmid40076446, year = {2025}, author = {Li, Y and Zhang, ZJ and Saarela, O and Sharma, D and Xu, W}, title = {Mediation CNN (Med-CNN) Model for High-Dimensional Mediation Data.}, journal = {International journal of molecular sciences}, volume = {26}, number = {5}, pages = {}, doi = {10.3390/ijms26051819}, pmid = {40076446}, issn = {1422-0067}, support = {RGPIN-2024-06081//Natural Sciences and Engineering Research Council/ ; }, mesh = {Humans ; *Algorithms ; *Neural Networks, Computer ; *Microbiota ; Female ; Computer Simulation ; }, abstract = {Complex biological features such as the human microbiome and gene expressions play a crucial role in human health by mediating various biomedical processes that influence disease progression, such as immune responses and metabolic processes. Understanding these mediation roles is essential for gaining insights into disease pathogenesis and improving treatment outcomes. However, analyzing such high-dimensional mediation features presents challenges due to their inherent structural and correlations, such as the hierarchical taxonomic structures in microbial operational taxonomic units (OTUs), gene-pathway relationships, and the high dimensionality of the datasets, which complicates mediation analysis. We propose the Med-CNN model, an iterative approach using Convolutional Neural Networks (CNNs) to incorporate the complex biological network of the mediation features. The output values from network-specific CNN models are condensed into an integrative mediation metric (IMM), which captures essential biological information for estimating mediation effects. Our approach is designed to handle high-dimensional data and accommodate their unique structures and non-linear interactive mediation effects. Through comprehensive simulation studies, we evaluated the performance of our algorithm across different scenarios, including various mediation effects, effect sizes, and sample sizes, and we compared it to conventional methods. Our simulations demonstrated consistently lower biases in mediation effect estimates, with values ranging from 0.17 to 0.56, which were lower than other established methods ranging from 0.24 to 13.27. In a real data application, our method identified a mediation effect of 0.06 between ethnicity and vaginal pH levels.}, }
@article {pmid40072660, year = {2025}, author = {Hu, J and Chen, W and Zhu, R and Yang, F and Xu, J and Xiang, B and Li, Y and Wang, W and Zhu, L and Chen, G and Zhi, M}, title = {Dietary risk factors in Crohn's disease and ulcerative colitis: a cohort study with paired healthy relatives as controls.}, journal = {European journal of nutrition}, volume = {64}, number = {3}, pages = {123}, pmid = {40072660}, issn = {1436-6215}, support = {2014008//Sun Yat-sen University Clinical Research 5010 Program/ ; 82170542//National Natural Science Foundation of China/ ; 92251307//National Natural Science Foundation of China/ ; 82270544//National Natural Science Foundation of China/ ; 2019ZT08Y464//Guangdong Province "Pearl River Talent Plan" Innovation and Entrepreneurship Team Project/ ; 2021YFF0703702//National Key Research and Development Program of China/ ; 2023YFF1104404//National Key Research and Development Program of China/ ; 2023AFD124//Hubei Provincial Natural Science Foundation of China/ ; }, mesh = {Humans ; *Crohn Disease/epidemiology ; *Colitis, Ulcerative/epidemiology ; Female ; Male ; Risk Factors ; Adult ; *Diet/methods/statistics &amp; numerical data ; Cohort Studies ; Middle Aged ; Case-Control Studies ; Family ; Feeding Behavior ; }, abstract = {PURPOSE: Conflicting results have been reported on dietary factors in inflammatory bowel diseases (IBDs). Here, we compared the dietary intakes of IBD patients with those of paired healthy relatives (HRs), aiming to minimize the impact of genetic and environmental confounders.<br><br>METHODS: Patients with Crohn's disease (CD, N&#x2009;=&#x2009;45) and ulcerative colitis (UC, N&#x2009;=&#x2009;20), their paired HRs (NCD-HR = 45, NUC-HR = 20) and healthy non-relative (HNR, NCD-HNR = 25, NUC-HNR = 55) controls were recruited. Participants have kept dietary habits since the onset of IBDs and report no other recent digestive diseases or surgeries. Pre-illness dietary factors were assessed through 24-hour recall interviews. Statistical analyses included Analysis of Variance, Fisher's exact tests, Wilcoxon rank sum tests, logistic regressions, Area Under the Receiver-Operator Curve (AUROC) analysis, and Least Absolute Shrinkage and Selection Operator (LASSO) regression.<br><br>RESULTS: Dietary features identified in IBD patients using the HR controls differed from those identified using the HNR controls. For CD, lower intakes of vitamin C, dietary fiber, calcium, vegetables, decanoic acid (10:0), milk, dairy foods, and &#x3b2;-carotene were identified as risk factors when compared to HRs. LASSO regression highlighted milk, vegetables, and vitamin C as the most significant risk factors for CD. In UC patients, lower intakes of phosphorus, docosapentaenoic acid (DPA, 22:5, n-3), vitamins B-2 and B-12, and choline, along with a higher intake of &#x3b1;-carotene, were identified as risk factors compared to HRs. LASSO regression emphasized DPA, vitamins B-2 and B-12, and &#x3b1;-carotene as the most significant risk factors for UC.<br><br>CONCLUSION: Monitoring dietary intake patterns is crucial for the prevention and personalized treatment of CD and UC.}, }
@article {pmid40072555, year = {2025}, author = {Shah, H and Patel, P and Nath, A and Shah, U and Sarkar, R}, title = {Role of human microbiota in facilitating the metastatic journey of cancer cells.}, journal = {Naunyn-Schmiedeberg's archives of pharmacology}, volume = {}, number = {}, pages = {}, pmid = {40072555}, issn = {1432-1912}, abstract = {Cancer continues to be the leading cause of mortality worldwide, with metastasis being the primary contributor to cancer-related deaths. Despite significant advancements in cancer therapies, metastasis remains a major challenge in effective cancer management. Metastasis, the process by which cancer cells spread from the primary tumor to distant organs, is a complex phenomenon influenced by multiple factors, including the human microbiota. The human body encompasses various microorganisms, comprising bacteria, viruses, fungi, and protozoa, collectively known as microbiota. In fact, the microbiota is more abundant than human cells, and its disruption, leading to an imbalance in host-microbiota interactions (dysbiosis), has been linked to various diseases, including cancer. Among all microbiota, bacteria are one of the key contributors to cancer progression. Bacteria and bacteria-derived components such as secondary metabolites, QSPs, and toxins play a pivotal role in the metastatic progression of cancers. This review explores the intricate relationship between the human microbiota and cancer progression, focusing on different bacterial species which have been implicated in tumorigenesis, immune evasion, and metastasis. The present review explores the role of the human microbiome, specifically of bacteria in promoting metastasis in different types of cancers, demonstrating its ability to impact both the spread of tumors and their underlying mechanisms. This review also highlights the therapeutic potential and challenges of microbiome-based interventions in combating metastatic cancers. By addressing these challenges and by integrating microbiome-targeted strategies into clinical cancer treatment could represent a transformative approach in the fight against metastasis.}, }
@article {pmid40069468, year = {2025}, author = {Yang, Y and Meng, Y and Xu, Z and Zhang, Q and Li, M and Kong, F and Zhang, S and Li, X and Zhu, Y}, title = {Leveraging microbiome signatures to predict tumor immune microenvironment and prognosis of patients with endometrial carcinoma.}, journal = {Discover oncology}, volume = {16}, number = {1}, pages = {299}, pmid = {40069468}, issn = {2730-6011}, support = {20214Y0226//Shanghai Municipal Health Commission/ ; 2024CRTS045//Sunshine Clinical Research Incubator Program/ ; 2024CRTS017//Sunshine Clinical Research Incubator Program/ ; 2024CRTS015//Sunshine Clinical Research Incubator Program/ ; }, abstract = {Recent studies suggest that the human microbiome influence tumor development. Endometrial carcinoma (EC) is the sixth most common malignancy in women. Recent research has demonstrated the microbes play a critical role in the development and metastasis of EC. However, it remains unclear whether intratumoral microbes are associated with tumor microenvironment (TME) and prognosis of EC. In this study, we collected the EC microbiome data from cBioPortal and constructed a prognostic model based on Resident Microbiome of Endometrium (RME). We then examined the relationship between the RME score, immune cell infiltration, immunotherapy-related signature, and prognosis. The findings demonstrated the independent prognostic value of the RME score for EC. The group with low RME scores had higher enrichment of immune cells. Drug sensitivity analysis revealed that the RME score may serve as a potential predictor of chemotherapy efficacy. In conclusion, our research offers new perspectives on the relationships between tumor immunity and microbes.}, }
@article {pmid40069378, year = {2025}, author = {Gulyaeva, K and Nadinskaia, M and Maslennikov, R and Aleshina, Y and Goptar, I and Lukashev, A and Poluektova, E and Ivashkin, V}, title = {Gut microbiota analysis in cirrhosis and non-cirrhotic portal hypertension suggests that portal hypertension can be main factor of cirrhosis-specific dysbiosis.}, journal = {Scientific reports}, volume = {15}, number = {1}, pages = {8394}, pmid = {40069378}, issn = {2045-2322}, support = {123021000156-7//Ministry of Health/ ; }, mesh = {Humans ; *Gastrointestinal Microbiome ; *Dysbiosis/microbiology ; Male ; Female ; *Hypertension, Portal/microbiology ; *Liver Cirrhosis/microbiology/complications ; Middle Aged ; Cross-Sectional Studies ; *RNA, Ribosomal, 16S/genetics ; Adult ; Aged ; Feces/microbiology ; Bacteria/classification/genetics/isolation &amp; purification ; Case-Control Studies ; }, abstract = {Gut dysbiosis plays an important role in cirrhosis, but the mechanism of its development was not established. The aim of the study was to test the hypothesis that portal hypertension can be the main factor in the development of gut dysbiosis in cirrhosis. This cross-sectional study included 25 patients with chronic non-cirrhotic portal hypertension due to extrahepatic portal vein obstruction after portal vein thrombosis (PVT) (NCPVT group), 29 cirrhotic patients without PVT (CirNoPVT), 15 cirrhotic patients with chronic PVT (CPVT), and 22 healthy controls. The fecal microbiota was assessed using 16S rRNA gene sequencing. The CirNoPVT and CPVT groups had largely similar differences in gut microbiota composition from the control group. Patients with NCPVT, as well as patients with cirrhosis, had a higher abundance of Streptococcus, Escherichia, Enterococcus, Enterobacteriaceae, Enterococcaceae, Streptococcaceae, Bacilli, Gammaproteobacteria, Proteobacteria, and a lower abundance of Roseburia, Faecalibacterium, Methanobrevibacter, Ruminococcaceae, Methanobacteriaceae, Clostridia, Methanobacteria, and Euryarchaeota as they were compared with healthy individuals. Patients with NCPVT had a higher abundance of Bifidobacterium, Bifidobacteriaceae, Actinobacteria, and a lower abundance of Gemmiger and Catenibacterium compared to healthy individuals, which was not observed in the cirrhosis groups. The abundance of Porphyromonadaceae with the genus Parabacteroides was reduced in both groups with PVT, but not in CirNoPVT. There were no significant differences in gut microbiota beta-diversity among the CirNoPVT, CPVT and NCPVT groups. All these groups had significant differences in beta-diversity from the control group. Portal hypertension seems be the main factor in the development of gut dysbiosis in cirrhosis.}, }
@article {pmid40059472, year = {2025}, author = {Elahi, Z and Mokhtaryan, M and Mahmoodi, S and Shahroodian, S and Darbandi, T and Ghasemi, F and Ghanavati, R and Darbandi, A}, title = {All Properties of Infertility Microbiome in a Review Article.}, journal = {Journal of clinical laboratory analysis}, volume = {}, number = {}, pages = {e25158}, doi = {10.1002/jcla.25158}, pmid = {40059472}, issn = {1098-2825}, support = {4150//Behbahan Faculty of Medical Sciences/ ; }, abstract = {BACKGROUND: The microbiome is crucial for many physiological processes, including immunity, metabolism, and reproduction.<br><br>AIMS: This review aims to contribute to a detailed understanding of the microbiome of the genital tract, which can lead to better management of dysbiosis and reproductive disorders.<br><br>METHODS: Data from the four international information databases Medline, Scopus, Embase, and Google Scholar. The search strategy was based on the combination of the following terms: "microbiota," "microbiome," "microfilm," "microflora," "fertility," or "infertility."<br><br>RESULT: The advent of next-generation sequencing-based technologies during the last decade has revealed the presence of microbial communities in nearly every part of the human body, including the reproductive system. Several studies have shown significant differences between the microbiota of the vagina and endometrium, as well as other parts of the upper genital tract.<br><br>DISCUSSION: The human microbiome plays a critical role in determining a person's health state, and the microbiome of the genital tract may impact fertility potential before and after assisted reproductive treatments (ARTs).<br><br>CONCLUSION: To completely understand the role of the microbiome, future research should focus not only on the description of microbiota but also on the interaction between bacteria, the production of biofilms, and the interaction of microorganisms with human cells.}, }
@article {pmid40055343, year = {2025}, author = {Qi, H and Gao, H and Li, M and Sun, T and Gu, X and Wei, L and Zhi, M and Li, Z and Fu, D and Liu, Y and Wei, Z and Dou, Y and Feng, Q}, title = {Parvimonas micra promotes oral squamous cell carcinoma metastasis through TmpC-CKAP4 axis.}, journal = {Nature communications}, volume = {16}, number = {1}, pages = {2305}, pmid = {40055343}, issn = {2041-1723}, support = {82270980//National Natural Science Foundation of China (National Science Foundation of China)/ ; }, mesh = {Humans ; *Mouth Neoplasms/pathology/metabolism/microbiology ; Animals ; Cell Line, Tumor ; Mice ; *Membrane Proteins/metabolism/genetics ; Carcinoma, Squamous Cell/metabolism/pathology/microbiology ; Neoplasm Metastasis ; Female ; Male ; Mice, Nude ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism ; Mice, Inbred BALB C ; Bacterial Proteins/metabolism/genetics ; Middle Aged ; Glycolysis ; }, abstract = {Parvimonas micra (P. micra), an opportunistic oral pathogen associated with multiple cancers, has limited research on its role in oral squamous cell carcinoma (OSCC). This study shows that P. micra is enriched in OSCC tissues and positively correlated with tumor metastasis and stages. P. micra infection promotes OSCC metastasis by inducing hypoxia/HIF-1α, glycolysis, and autophagy. Mechanistically, P. micra surface protein TmpC binds to CKAP4, a receptor overexpressed in OSCC, facilitating bacterial attachment and invasion. This interaction activates HIF-1α and autophagy via CKAP4-RanBP2 and CKAP4-NBR1 pathways, driving metastasis. Targeting CKAP4 with masitinib or antibodies impairs P. micra attachment and abolishes P. micra-promoted OSCC metastasis in vitro and in vivo. Together, our findings identify P. micra as a pathogen that promotes OSCC metastasis and highlight that TmpC-CKAP4 interaction could be a potential therapeutic target for OSCC.}, }
@article {pmid40054744, year = {2025}, author = {Fyhrquist, N and Yang, Y and Karisola, P and Alenius, H}, title = {Endotypes of Atopic Dermatitis.}, journal = {The Journal of allergy and clinical immunology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jaci.2025.02.029}, pmid = {40054744}, issn = {1097-6825}, abstract = {Atopic dermatitis (AD) is a chronic, heterogeneous skin condition driven by a combination of genetic, immune, and environmental factors. The original classification into extrinsic and intrinsic endotypes has proven overly simplistic. Recent research into the varied immune profiles and molecular signatures of AD has revealed distinct endotypes - subtypes defined by specific biological processes rather than visible symptoms alone. These endotypes encompass classifications based on immune pathways, including Th2-dominant, Th1, Th17/Th22-driven responses, genetic factors, and microbial interactions. Recognizing these endotypes has become essential for advancing personalized treatments, as each subtype responds differently to immune-modulating therapies. Current treatment options, such as moisturizers, immunosuppressants, and biologics, show varied efficacy across AD endotypes, underscoring the need for more precise, endotype-specific approaches. Emerging molecular profiling technologies offer promising avenues to identify distinct biomarkers, refining AD classification and paving the way for more targeted treatments and improved patient outcomes.}, }
@article {pmid40051624, year = {2025}, author = {De Martinis, ECP and Alves, VF and Pereira, MG and Andrade, LN and Abichabki, N and Abramova, A and Dannborg, M and Bengtsson-Palme, J}, title = {Applying 3D cultures and high-throughput technologies to study host-pathogen interactions.}, journal = {Frontiers in immunology}, volume = {16}, number = {}, pages = {1488699}, pmid = {40051624}, issn = {1664-3224}, mesh = {Humans ; *Host-Pathogen Interactions ; *Cell Culture Techniques, Three Dimensional/methods ; Animals ; High-Throughput Screening Assays/methods ; Microbiota ; High-Throughput Nucleotide Sequencing ; }, abstract = {Recent advances in cell culturing and DNA sequencing have dramatically altered the field of human microbiome research. Three-dimensional (3D) cell culture is an important tool in cell biology, in cancer research, and for studying host-microbe interactions, as it mimics the in vivo characteristics of the host environment in an in vitro system, providing reliable and reproducible models. This work provides an overview of the main 3D culture techniques applied to study interactions between host cells and pathogenic microorganisms, how these systems can be integrated with high-throughput molecular methods, and how multi-species model systems may pave the way forward to pinpoint interactions among host, beneficial microbes and pathogens.}, }
@article {pmid40048849, year = {2025}, author = {Bargheet, A and Noordzij, HT and Ponsero, AJ and Jian, C and Korpela, K and Valles-Colomer, M and Debelius, J and Kurilshikov, A and Pettersen, VK}, title = {Dynamics of gut resistome and mobilome in early life: a meta-analysis.}, journal = {EBioMedicine}, volume = {114}, number = {}, pages = {105630}, doi = {10.1016/j.ebiom.2025.105630}, pmid = {40048849}, issn = {2352-3964}, abstract = {BACKGROUND: The gut microbiota of infants harbours a higher proportion of antibiotic resistance genes (ARGs) compared to adults, even in infants never exposed to antibiotics. Our study aims to elucidate this phenomenon by analysing how different perinatal factors influence the presence of ARGs, mobile genetic elements (MGEs), and their bacterial hosts in the infant gut.<br><br>METHODS: We searched MEDLINE and Embase up to April 3rd, 2023, for studies reporting infant cohorts with shotgun metagenomic sequencing of stool samples. The systematic search identified 14 longitudinal infant cohorts from 10 countries across three continents, featuring publicly available sequencing data with corresponding metadata. For subsequent integrative bioinformatic analyses, we used 3981 high-quality metagenomic samples from 1270 infants and 415 mothers.<br><br>FINDINGS: We identified distinct trajectories of the resistome and mobilome associated with birth mode, gestational age, antibiotic use, and geographical location. Geographical variation was exemplified by differences between cohorts from Europe, Southern Africa, and Northern America, which showed variation in both diversity and abundance of ARGs. On the other hand, we did not detect a significant impact of breastfeeding on the infants' gut resistome. More than half of detected ARGs co-localised with plasmids in key bacterial hosts, such as Escherichia coli and Enterococcus faecalis. These ARG-associated plasmids were gradually lost during infancy. We also demonstrate that E.&#xa0;coli role as a primary modulator of the infant gut resistome and mobilome is facilitated by its increased abundance and strain diversity compared to adults.<br><br>INTERPRETATION: Birth mode, gestational age, antibiotic exposure, and geographical location significantly influence the development of the infant gut resistome and mobilome. A reduction in E. coli relative abundance over time appears as a key factor driving the decrease in both resistome and plasmid relative abundance as infants grow.<br><br>FUNDING: Centre for Advanced Study in Oslo, Norway. Centre for New Antibacterial Strategies through the Troms&#xf8; Research Foundation, Norway.}, }
@article {pmid40040485, year = {2025}, author = {Wang, Y and Li, B and Jian, C and Gagaoua, M and Estévez, M and Puolanne, E and Ertbjerg, P}, title = {Oxidative stress-induced changes in wooden breast and mitigation strategies: A review.}, journal = {Comprehensive reviews in food science and food safety}, volume = {24}, number = {2}, pages = {e70148}, doi = {10.1111/1541-4337.70148}, pmid = {40040485}, issn = {1541-4337}, support = {348385//Research Council of Finland/ ; }, mesh = {*Oxidative Stress ; Animals ; Poultry Diseases/microbiology/prevention &amp; control ; Meat ; Chickens ; Muscular Diseases ; }, abstract = {Wooden breast (WB) is a multifactorial muscular abnormality resulting from the interplay between genetic predispositions for rapid growth, physiological stress, and anatomical impairments. This myopathy has been a persistent challenge in the poultry industry since its initial identification a decade ago. WB negatively impacts meat quality, leading to increased toughness and reduced nutritional value. Building on foundational research utilizing multiomics technologies, hypoxia-induced oxidative stress has been identified as a key early event driving the pathological processes of WB. This review provides a comprehensive overview and the state-of-the-art evidence on the pivotal role of oxidative stress in WB myopathy. It begins by examining the generation of reactive intermediates that induce oxidative damage and the host's defense mechanisms aimed at mitigating these threats. The discussion then focuses on the consequences of oxidative damage for mitochondria, protein and lipid oxidation, connective tissue remodeling, and inflammation-pathological hallmarks of WB-affected muscles. Additionally, the review highlights how oxidative stress influences satellite cell behavior, impairing the repair and regeneration of muscle tissues, a process implicated in WB. Finally, efforts to prevent or mitigate WB myopathy are summarized, with particular attention to potential intervention strategies targeting oxidative stress. These include innovative feed formulations and gut microbiota modulation, which show promise in alleviating the severity of the condition.}, }
@article {pmid40033410, year = {2025}, author = {Ranta, K and Skurnik, M and Kiljunen, S}, title = {Isolation and characterization of fMGyn-Pae01, a phiKZ-like jumbo phage infecting Pseudomonas aeruginosa.}, journal = {Virology journal}, volume = {22}, number = {1}, pages = {55}, pmid = {40033410}, issn = {1743-422X}, mesh = {*Pseudomonas aeruginosa/virology/drug effects ; *Host Specificity ; *Genome, Viral ; *Pseudomonas Phages/genetics/isolation &amp; purification/physiology/classification ; Biofilms/growth &amp; development ; Whole Genome Sequencing ; Phage Therapy ; Microscopy, Electron, Transmission ; }, abstract = {BACKGROUND: Pseudomonas aeruginosa is an opportunistic pathogen that causes a wide variety of infections, and belongs to the group of ESKAPE pathogens that are the leading cause of healthcare-associated infections and have high level of antibiotic resistance. The treatment of infections caused by antibiotic-resistant P. aeruginosa is challenging, which makes it a common target for phage therapy. The successful utilization of phage therapy requires a collection of well characterized phages.<br><br>METHODS: Phage fMGyn-Pae01 was isolated from a commercial phage therapy cocktail. The phage morphology was studied by transmission electron microscopy and the host range was analyzed with a liquid culture method. The phage genome was sequenced and characterized, and the genome was compared to closest phage genomes. Phage resistant bacterial mutants were isolated and whole genome sequencing and motility, phage adsorption and biofilm formation assays were performed to the mutants and host bacterium.<br><br>RESULTS: The genomic analysis revealed that fMGyn-Pae01 is a lytic, phiKZ-like jumbo phage with genome size of 277.8&#xa0;kb. No genes associated with lysogeny, bacterial virulence, or antibiotic resistance were identified. Phage fMGyn-Pae01 did not reduce biofilm formation of P. aeruginosa, suggesting that it may not be an optimal phage to be used in monophage therapy in conditions where biofilm formation is expected. Host range screening revealed that fMGyn-Pae01 has a wide host range among P. aeruginosa strains and its infection was not dependent on O-serotype. Whole genome sequencing of the host bacterium and phage resistant mutants revealed that the mutations had inactivated either a flagellar or rpoN gene, thereby preventing the biosynthesis of a functional flagellum. The lack of functional flagella was confirmed in motility assays. Additionally, fMGyn-Pae01 failed to adsorb on non-motile mutants indicating that the bacterial flagellum is the phage-binding receptor.<br><br>CONCLUSION: fMGyn-Pae01 is a phiKZ-like jumbo phage infecting P. aeruginosa. fMGyn-Pae01 uses the flagellum as its phage-binding receptor, supporting earlier suggestions that flagellum might be utilized by phiKZ but differs from some other previous findings showing that phiKZ-like phages use the type-IV pili as the phage-binding receptor.}, }
@article {pmid40033063, year = {2025}, author = {Metwaly, A and Kriaa, A and Hassani, Z and Carraturo, F and Druart, C and ,  and Arnauts, K and Wilmes, P and Walter, J and Rosshart, S and Desai, MS and Dore, J and Blottiere, HM and Maguin, E and Haller, D}, title = {A Consensus Statement on establishing causality, therapeutic applications and the use of preclinical models in microbiome research.}, journal = {Nature reviews. Gastroenterology &amp; hepatology}, volume = {}, number = {}, pages = {}, pmid = {40033063}, issn = {1759-5053}, abstract = {The gut microbiome comprises trillions of microorganisms and profoundly influences human health by modulating metabolism, immune responses and neuronal functions. Disruption in gut microbiome composition is implicated in various inflammatory conditions, metabolic disorders and neurodegenerative diseases. However, determining the underlying mechanisms and establishing cause and effect is extremely difficult. Preclinical models offer crucial insights into the role of the gut microbiome in diseases and help identify potential therapeutic interventions. The Human Microbiome Action Consortium initiated a Delphi survey to assess the utility of preclinical models, including animal and cell-based models, in elucidating the causal role of the gut microbiome in these diseases. The Delphi survey aimed to address the complexity of selecting appropriate preclinical models to investigate disease causality and to study host-microbiome interactions effectively. We adopted a structured approach encompassing a literature review, expert workshops and the Delphi questionnaire to gather insights from a diverse range of stakeholders. Experts were requested to evaluate the strengths, limitations, and suitability of these models in addressing the causal relationship between the gut microbiome and disease pathogenesis. The resulting consensus statements and recommendations provide valuable insights for selecting preclinical models in future studies of gut microbiome-related diseases.}, }
@article {pmid40030005, year = {2025}, author = {Darwin, A and Xie, J and Smith, M}, title = {Antibiotic Use: Impact on the Microbiome and Cellular Therapy Outcomes.}, journal = {Blood advances}, volume = {}, number = {}, pages = {}, doi = {10.1182/bloodadvances.2024013809}, pmid = {40030005}, issn = {2473-9537}, abstract = {Antibiotics disrupt the delicate balance of bacteria, fungi, and viruses in the human microbiome. Growing evidence indicates a significant relationship between the intestinal microbiome and cellular therapy, which aligns with the established influence of the microbiome on immune responses. When examining the link between cellular therapy and the microbiome, it is essential to understand how disruptions in the microbiome-especially those caused by antibiotics-affect these therapies. Here, we discuss the impact of antibiotics on the intestinal microbiome, cellular therapy outcomes, and associated toxicities, particularly in the context of hematopoietic cell transplantation and chimeric antigen receptor T-cell therapy. Furthermore, we examine the mechanisms through which antibiotics affect cellular therapy, the future implications of this knowledge, and the areas that warrant further investigation.}, }
@article {pmid40026151, year = {2025}, author = {Jena, PK and Wakita, D and Gomez, AC and Carvalho, TT and Atici, AE and Aubuchon, E and Narayanan, M and Lee, Y and Fishbein, MC and Takasato, Y and Kurashima, Y and Kiyono, H and Cani, PD and de Vos, WM and Underhill, DM and Devkota, S and Chen, S and Shimada, K and Crother, TR and Arditi, M and Noval Rivas, M}, title = {Intestinal Microbiota Contributes to the Development of Cardiovascular Inflammation and Vasculitis in Mice.}, journal = {Circulation research}, volume = {}, number = {}, pages = {}, doi = {10.1161/CIRCRESAHA.124.325079}, pmid = {40026151}, issn = {1524-4571}, abstract = {BACKGROUND: Alterations in the intestinal microbiota contribute to the pathogenesis of various cardiovascular disorders, but how they affect the development of Kawasaki disease, an acute pediatric vasculitis, remains unclear. Here, using a murine model mimicking Kawasaki disease vasculitis, we assessed the contribution of the intestinal microbiota to the development of vascular inflammation.<br><br>METHODS AND RESULTS: We report that depleting the gut microbiota reduces the development of cardiovascular inflammation in a murine model mimicking Kawasaki disease vasculitis. The development of cardiovascular lesions was associated with alterations in the intestinal microbiota composition and, notably, a decreased abundance of Akkermansia muciniphila and Faecalibacterium prausnitzii. Oral supplementation with either of these live or pasteurized individual bacteria or with short-chain fatty acids produced by them attenuated cardiovascular inflammation, as reflected by decreased local immune cell infiltrations. Treatment with Amuc_1100, the TLR-2 signaling outer membrane protein from Akkermansia muciniphila, also reduced the severity of vascular inflammation.<br><br>CONCLUSIONS: This study reveals an underappreciated gut microbiota-cardiovascular inflammation axis in Kawasaki disease vasculitis pathogenesis and identifies specific intestinal commensals that regulate vasculitis in mice by producing metabolites or via extracellular proteins capable of enhancing and supporting gut barrier function.}, }
@article {pmid40023841, year = {2025}, author = {Pérez Escriva, P and Correia Tavares Bernardino, C and Letellier, E}, title = {De-coding the complex role of microbial metabolites in cancer.}, journal = {Cell reports}, volume = {44}, number = {3}, pages = {115358}, doi = {10.1016/j.celrep.2025.115358}, pmid = {40023841}, issn = {2211-1247}, abstract = {The human microbiome, an intricate ecosystem of trillions of microbes residing across various body sites, significantly influences cancer, a leading cause of morbidity and mortality worldwide. Recent studies have illuminated the microbiome's pivotal role in cancer development, either through direct cellular interactions or by secreting bioactive compounds such as metabolites. Microbial metabolites contribute to cancer initiation through mechanisms such as DNA damage, epithelial barrier dysfunction, and chronic inflammation. Furthermore, microbial metabolites exert dual roles on cancer progression and response to therapy by modulating cellular metabolism, gene expression, and signaling pathways. Understanding these complex interactions is vital for devising new therapeutic strategies. This review highlights microbial metabolites as promising targets for cancer prevention and treatment, emphasizing their impact on therapy responses and underscoring the need for further research into their roles in metastasis and therapy resistance.}, }
@article {pmid40023356, year = {2025}, author = {Das, M and Kiruthiga, C and Shafreen, RB and Nachammai, KT and Selvaraj, C and Langeswaran, K}, title = {Harnessing the Human Microbiome and its Impact on Immuno-Oncology and Nanotechnology for Next-Generation Cancer Therapies.}, journal = {European journal of pharmacology}, volume = {}, number = {}, pages = {177436}, doi = {10.1016/j.ejphar.2025.177436}, pmid = {40023356}, issn = {1879-0712}, abstract = {The integration of microbiome research and nanotechnology represents a significant advancement in immuno-oncology, potentially improving the effectiveness of cancer immunotherapies. Recent studies highlight the influential role of the human microbiome in modulating immune responses, presenting new opportunities to enhance immune checkpoint inhibitors (ICIs) and other cancer therapies. Nanotechnology offers precise drug delivery and immune modulation capabilities, minimizing off-target effects while maximizing therapeutic outcomes. This review consolidates current knowledge on the interactions between the microbiome and the immune system, emphasizing the microbiome's impact on ICIs, and explores the incorporation of nanotechnology in cancer treatment strategies. Additionally, it provides a forward-looking perspective on the synergistic potential of microbiome modulation and nanotechnology to overcome existing challenges in immuno-oncology. This integrated approach may enhance the personalization and effectiveness of next-generation cancer treatments, paving the way for transformative patient care.}, }
@article {pmid40019912, year = {2025}, author = {Ryan, N and O'Mahony, S and Leahy-Warren, P and Philpott, L and Mulcahy, H}, title = {The impact of perinatal maternal stress on the maternal and infant gut and human milk microbiomes: A scoping review.}, journal = {PloS one}, volume = {20}, number = {2}, pages = {e0318237}, doi = {10.1371/journal.pone.0318237}, pmid = {40019912}, issn = {1932-6203}, mesh = {Humans ; *Milk, Human/microbiology ; Female ; Pregnancy ; *Gastrointestinal Microbiome ; *Stress, Psychological/microbiology ; Infant ; Infant, Newborn ; }, abstract = {BACKGROUND: Perinatal maternal stress, which includes both psychological and physiological stress experienced by healthy women during pregnancy and the postpartum period, is becoming increasingly prevalent. Infant early exposure to adverse environments such as perinatal stress has been shown to increase the long-term risk to metabolic, immunologic and neurobehavioral disorders. Evidence suggests that the human microbiome facilitates the transmission of maternal factors to infants via the vaginal, gut, and human milk microbiomes. The colonization of aberrant microorganisms in the mother's microbiome, influenced by the microbiome-brain-gut axis, may be transferred to infants during a critical early developmental period. This transfer may predispose infants to a more inflammatory-prone microbiome which is associated with dysregulated metabolic process leading to adverse health outcomes. Given the prevalence and potential impact of perinatal stress on maternal and infant health, with no systematic mapping or review of the data to date, the aim of this scoping review is to gather evidence on the relationship between perinatal maternal stress, and the human milk, maternal, and infant gut microbiomes.<br><br>METHODS: This is an exploratory mapping scoping review, guided by the Joanna Briggs Institute's methodology along with use of the Prisma Scr reporting guideline. A comprehensive search was conducted using the following databases, CINAHL Complete; MEDLINE; PsycINFO, Web of Science and Scopus with a protocol registered with Open Science Framework DOI 10.17605/OSF.IO/5SRMV.<br><br>RESULTS: After screening 1145 papers there were 7 paper that met the inclusion criteria. Statistically significant associations were found in five of the studies which identify higher abundance of potentially pathogenic bacteria such as Erwinia, Serratia, T mayombie, Bacteroides with higher maternal stress, and lower levels of stress linked to potentially beneficial bacteria such Lactococcus, Lactobacillus, Akkermansia. However, one study presents conflicting results where it was reported that higher maternal stress was linked to the prevalence of more beneficial bacteria.<br><br>CONCLUSION: This review suggests that maternal stress does have an impact on the alteration of abundance and diversity of influential bacteria in the gut microbiome, however, it can affect colonisation in different ways. These bacterial changes have the capacity to influence long term health and disease. The review analyses data collection tools and methods, offers potential reasons for these findings as well as suggestions for future research.}, }
@article {pmid40016751, year = {2025}, author = {Gan, Y and Yuan, Z and Weng, J and Huang, M and Li, T and Wu, Y and Lin, K and Han, J and Li, X and Liu, H and Wan, Z and Li, Z and Chen, Z and Cui, J and Luo, Y and Huang, M and Yu, H and Lin, J}, title = {Transcriptomic profile of RNA pseudouridine modification as a biomarker for cellular senescence associated with survival outcomes in colorectal cancer.}, journal = {BMC biology}, volume = {23}, number = {1}, pages = {61}, pmid = {40016751}, issn = {1741-7007}, abstract = {BACKGROUND: Colorectal cancer (CRC) is considered as an age-related disease, and cellular senescence (CS) plays a crucial role in cancer development and progression. Previous studies have shown the role of epigenetic changes in aging and cancer development, but the role of RNA pseudouridine (Ψ) modification in aging and cancer remains to be explored.<br><br>RESULTS: Using bulk RNA sequencing, CRC cells with low &#x3a8; writers expression levels have higher CS levels. We developed the Psi Score for assessing the transcriptomic profile of RNA &#x3a8; modification regulation and found that the Psi Score correlates with CS. Furthermore, Psi-related senescence may be mediated by mTOR, TGF-&#x3b2;, TNF-&#x3b1;, and inflammatory response signaling pathways. Meanwhile, Psi Score could predict the anti-cancer treatment outcomes of anti-aging interventions and could be used to predict the response to immunotherapy.<br><br>CONCLUSIONS: Overall, these findings reveal that RNA &#x3a8; modification connected aging and cancer and provided novel insights into biomarker-guided cancer regimens.}, }
@article {pmid40016656, year = {2025}, author = {Koslovsky, MD}, title = {Analyzing microbiome data with taxonomic misclassification using a zero-inflated Dirichlet-multinomial model.}, journal = {BMC bioinformatics}, volume = {26}, number = {1}, pages = {69}, pmid = {40016656}, issn = {1471-2105}, support = {DMS-2245492//National Science Foundation/ ; }, abstract = {The human microbiome is the collection of microorganisms living on and inside of our bodies. A major aim of microbiome research is understanding the role microbial communities play in human health with the goal of designing personalized interventions that modulate the microbiome to treat or prevent disease. Microbiome data are challenging to analyze due to their high-dimensionality, overdispersion, and zero-inflation. Analysis is further complicated by the steps taken to collect and process microbiome samples. For example, sequencing instruments have a fixed capacity for the total number of reads delivered. It is therefore essential to treat microbial samples as compositional. Another complicating factor of modeling microbiome data is that taxa counts are subject to measurement error introduced at various stages of the measurement protocol. Advances in sequencing technology and preprocessing pipelines coupled with our growing knowledge of the human microbiome have reduced, but not eliminated, measurement error. Ignoring measurement error during analysis, though common in practice, can then lead to biased inference and curb reproducibility. We propose a Dirichlet-multinomial modeling framework for microbiome data with excess zeros and potential taxonomic misclassification. We demonstrate how accommodating taxonomic misclassification improves estimation performance and investigate differences in gut microbial composition between healthy and obese children.}, }
@article {pmid40009328, year = {2025}, author = {Mivehchi, H and Eskandari-Yaghbastlo, A and Pour Bahrami, P and Elhami, A and Faghihinia, F and Nejati, ST and Kazemi, KS and Nabi Afjadi, M}, title = {Exploring the role of oral bacteria in oral cancer: a narrative review.}, journal = {Discover oncology}, volume = {16}, number = {1}, pages = {242}, pmid = {40009328}, issn = {2730-6011}, abstract = {A growing body of research indicates that a wide range of cancer types may correlate with human microbiome components. On the other hand, little is known about the potential contribution of the oral microbiota to oral cancer. However, some oral microbiome components can stimulate different tumorigenic processes associated with the development of cancer. In this line, two prevalent oral infections, Porphyromonas gingivalis, and Fusobacterium nucleatum can increase tumor growth. The microbiome can impact the course of the illness through direct interactions with the human body and major modifications to the toxicity and responsiveness to different kinds of cancer therapy. Recent research has demonstrated a relationship between specific phylogenetic groupings and the results of immunotherapy treatment for particular tumor types. Conversely, there has been a recent upsurge in interest in the possibility of using microbes to treat cancer. At the moment, some species, such as Salmonella typhimurium and Clostridium spp., are being explored as possible cancer treatment vectors. Thus, understanding these microbial interactions highlights the importance of maintaining a healthy oral microbiome in preventing oral cancers. From this perspective, this review will discuss the role of the microbiome on oral cancers and their possible application in oral cancer treatment/improvement.}, }
@article {pmid40005682, year = {2025}, author = {Ece, G and Aktaş, A and Caner, A and Sağlık, &#x130; and Kula Atik, T and Ulusan Bağcı, &#xd6; and Bayındır Bilman, F and Demirbakan, H and Güdül Havuz, S and Kaya, E and Koyuncu Özyurt, &#xd6; and Yetkin, G and Zorbozan, O}, title = {The Urogenital System Microbiota: Is It a New Gamechanger in Urogenital Cancers?.}, journal = {Microorganisms}, volume = {13}, number = {2}, pages = {}, doi = {10.3390/microorganisms13020315}, pmid = {40005682}, issn = {2076-2607}, abstract = {The human microbiome, which encompasses microbial communities and their genetic material, significantly influences health and disease, including cancer. The urogenital microbiota, naturally present in the urinary and genital tracts, interact with factors such as age, lifestyle, and health conditions to affect homeostasis and carcinogenesis. Studies suggest that alterations in this microbiota contribute to the development and progression of genitourinary cancers, emphasizing the concept of oncobiome, which refers to microbial genetic contributions to cancer. Similarly, gut microbiota can influence hormone levels and systemic inflammation, impacting cancers such as cervical and prostate cancer. Advanced studies indicate that microbial communities in genitourinary cancers have distinct profiles that may serve as diagnostic biomarkers or therapeutic targets. Dysbiosis of the urinary microbiota correlates with bladder and kidney cancer. Additionally, gut microbiota influence the effectiveness of cancer treatments. However, further research is necessary to clarify causality, the role of microbial metabolites, and hormonal regulation. The aim of this review is to understand that these dynamics present opportunities for innovative cancer diagnostics and therapies, highlighting the need for integration of microbiology, oncology, and genomics to explore the role of microbiota in genitourinary cancers. For this, a comprehensive search of relevant databases was conducted, applying specific inclusion and exclusion criteria to identify studies examining the association between microbiota and urogenital cancers. Research into the mechanisms by which microbiota influence urogenital cancers may pave the way for new diagnostic and therapeutic approaches, ultimately improving patient outcomes.}, }
@article {pmid40005646, year = {2025}, author = {Choi, Y and Jeong, J and Han, Y and Han, M and Yu, B and Han, K}, title = {Exploring Competitive Relationship Between Haemophilus parainfluenzae and Mitis Streptococci via Co-Culture-Based Molecular Diagnosis and Metabolomic Assay.}, journal = {Microorganisms}, volume = {13}, number = {2}, pages = {}, doi = {10.3390/microorganisms13020279}, pmid = {40005646}, issn = {2076-2607}, support = {RS-2024-00355393//the Ministry of Education of the Republic of Korea and the National Research Foundation of Korea/ ; }, abstract = {Various bacterial strains with nitrate-reducing capacity (NRC), such as Haemophilus, Actinomyces, and Neisseria, are known to promote NH3 production, control pH in the oral cavity, and inhibit the growth of aciduric bacteria. However, experimental evidence on various estimated bacterial networks within the salivary microbiome is insufficient. This study aims to explore potential bacterial compositional competition observed within saliva samples from dental caries patients through a co-culture assay of mitis Streptococci, which is a primary colonizer in the salivary microbiome, and nitrate-reducing bacteria Haemophilus parainfluenzae. We investigated bacterial growth efficiency change by co-culture time using the qRT-PCR method. In addition, we applied LC/Q-TOF-based metabolites screening to confirm metabolic interactions between oral bacterial species and their association with dental caries from a metabolomics perspective. As a result, we first found that the nitrate reduction ability of H. parainfluenzae is maintained even in a co-culture environment with the mitis Streptococci group through a nitrate reduction test. However, nitrate reduction efficiency was hindered when compared with monoculture-based nitrate reduction test results. Next, we designed species-specific primers, and we confirmed by qRT-PCR that there is an obvious competitive relationship in growth efficiency between H. parainfluenzae and two mitis Streptococci (S. australis and S. sanguinis). Furthermore, although direct effects of nitrate reduction on competition have not been identified, we have potentially confirmed through LC/Q-TOF-based metabolite screening analysis that the interaction of various metabolic compounds synthesized from mitis Streptococci is driving inter-strain competition. In particular, we constructed a basic reference core-metabolites list to understand the metabolic network between each target bacterial species (H. parainfluenzae and mitis Streptococci) within the salivary microbiome, which still lacks accumulated research data. Ultimately, we suggest that our data have potential value to be referenced in further metagenomics and metabolomics-based studies related to oral health care.}, }
@article {pmid39999339, year = {2025}, author = {Hohmann, M and Iliasov, D and Larralde, M and Johannes, W and Janßen, KP and Zeller, G and Mascher, T and Gulder, TAM}, title = {Heterologous Expression of a Cryptic BGC from Bilophila sp. Provides Access to a Novel Family of Antibacterial Thiazoles.}, journal = {ACS synthetic biology}, volume = {}, number = {}, pages = {}, doi = {10.1021/acssynbio.5c00042}, pmid = {39999339}, issn = {2161-5063}, abstract = {Human health is greatly influenced by the gut microbiota and microbiota imbalance can lead to the development of diseases. It is widely acknowledged that the interaction of bacteria within competitive ecosystems is influenced by their specialized metabolites, which act, e.g., as antibacterials or siderophores. However, our understanding of the occurrence and impact of such natural products in the human gut microbiome remains very limited. As arylthiazole siderophores are an emerging family of growth-promoting molecules in pathogenic bacteria, we analyzed a metagenomic data set from the human microbiome and thereby identified the bil-BGC, which originates from an uncultured Bilophila strain. Through gene synthesis and BGC assembly, heterologous expression and mutasynthetic experiments, we discovered the arylthiazole natural products bilothiazoles A-F. While established activities of related molecules indicate their involvement in metal-binding and -uptake, which could promote the growth of pathogenic strains, we also found antibiotic activity for some bilothiazoles. This is supported by biosensor-experiments, where bilothiazoles C and E show PrecA-suppressing activity, while bilothiazole F induces PblaZ, a biosensor characteristic for β-lactam antibiotics. These findings serve as a starting point for investigating the role of bilothiazoles in the pathogenicity of Bilophila species in the gut.}, }
@article {pmid39998261, year = {2025}, author = {Woh, PY and Chen, Y and Kumpitsch, C and Mohammadzadeh, R and Schmidt, L and Moissl-Eichinger, C}, title = {Reevaluation of the gastrointestinal methanogenic archaeome in multiple sclerosis and its association with treatment.}, journal = {Microbiology spectrum}, volume = {}, number = {}, pages = {e0218324}, doi = {10.1128/spectrum.02183-24}, pmid = {39998261}, issn = {2165-0497}, abstract = {The role of the gut archaeal microbiome (archaeome) in health and disease remains poorly understood. Methanogenic archaea have been linked to multiple sclerosis (MS), but prior studies were limited by small cohorts and inconsistent methodologies. To address this, we re-evaluated the association between methanogenic archaea and MS using metagenomic data from the International Multiple Sclerosis Microbiome Study. We analyzed gut microbiome profiles from 115 MS patients and 115 healthy household controls across Buenos Aires (27.8%), Edinburgh (33.9%), New York (10.4%), and San Francisco (27.8%). Metagenomic sequences were taxonomically classified using kraken2/bracken and a curated profiling database to detect archaea, specifically Methanobrevibacter species. Most MS patients were female (80/115), aged 25-72 years (median: 44.5), and 70% were undergoing treatment, including dimethyl fumarate (n = 21), fingolimod (n = 20), glatiramer acetate (n = 14), interferon (n = 18), natalizumab (n = 6), or ocrelizumab/rituximab (n = 1). We found no significant differences in overall archaeome profiles between MS patients and controls. However, treated MS patients exhibited higher abundances of Methanobrevibacter smithii and M. sp900766745 compared to untreated patients. Notably, M. sp900766745 abundance correlated with lower disease severity scores in treated patients. Our results suggest that gut methanogens are not directly associated with MS onset or progression but may reflect microbiome health during treatment. These findings highlight potential roles for M. smithii and M. sp900766745 in modulating treatment outcomes, warranting further investigation into their relevance to gut microbiome function and MS management.IMPORTANCEMultiple sclerosis (MS) is a chronic neuroinflammatory disease affecting the central nervous system, with approximately 2.8 million people diagnosed worldwide, mainly young adults aged 20-30 years. While recent studies have focused on bacterial changes in the MS microbiome, the role of gut archaea has been less explored. Previous research suggested a potential link between methanogenic archaea and MS disease status, but these findings remained inconclusive. Our study addresses this gap by investigating the gut archaeal composition in MS patients and examining how it changes in response to treatment. By focusing on methanogens, we aim to uncover novel insights into their role in MS, potentially revealing new biomarkers or therapeutic targets. This research is crucial for enhancing our understanding of the gut microbiome's impact on MS and improving patient management.}, }
@article {pmid39998226, year = {2025}, author = {Martino, C and Kellman, BP and Sandoval, DR and Clausen, TM and Cooper, R and Benjdia, A and Soualmia, F and Clark, AE and Garretson, AF and Marotz, CA and Song, SJ and Wandro, S and Zaramela, LS and Salido, RA and Zhu, Q and Armingol, E and Vázquez-Baeza, Y and McDonald, D and Sorrentino, JT and Taylor, B and Belda-Ferre, P and Das, P and Ali, F and Liang, C and Zhang, Y and Schifanella, L and Covizzi, A and Lai, A and Riva, A and Basting, C and Broedlow, CA and Havulinna, AS and Jousilahti, P and Estaki, M and Kosciolek, T and Kuplicki, R and Victor, TA and Paulus, MP and Savage, KE and Benbow, JL and Spielfogel, ES and Anderson, CAM and Martinez, ME and Lacey, JV and Huang, S and Haiminen, N and Parida, L and Kim, H-C and Gilbert, JA and Sweeney, DA and Allard, SM and Swafford, AD and Cheng, S and Inoyue, M and Niiranen, T and Jain, M and Salomaa, V and Zengler, K and Klatt, NR and Hasty, J and Berteau, O and Carlin, AF and Esko, JD and Lewis, NE and Knight, R}, title = {SARS-CoV-2 infectivity can be modulated through bacterial grooming of the glycocalyx.}, journal = {mBio}, volume = {}, number = {}, pages = {e0401524}, doi = {10.1128/mbio.04015-24}, pmid = {39998226}, issn = {2150-7511}, abstract = {The gastrointestinal (GI) tract is a site of replication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and GI symptoms are often reported by patients. SARS-CoV-2 cell entry depends upon heparan sulfate (HS) proteoglycans, which commensal bacteria that bathe the human mucosa are known to modify. To explore human gut HS-modifying bacterial abundances and how their presence may impact SARS-CoV-2 infection, we developed a task-based analysis of proteoglycan degradation on large-scale shotgun metagenomic data. We observed that gut bacteria with high predicted catabolic capacity for HS differ by age and sex, factors associated with coronavirus disease 2019 (COVID-19) severity, and directly by disease severity during/after infection, but do not vary between subjects with COVID-19 comorbidities or by diet. Gut commensal bacterial HS-modifying enzymes reduce spike protein binding and infection of authentic SARS-CoV-2, suggesting that bacterial grooming of the GI mucosa may impact viral susceptibility.IMPORTANCESevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for coronavirus disease 2019, can infect the gastrointestinal (GI) tract, and individuals who exhibit GI symptoms often have more severe disease. The GI tract's glycocalyx, a component of the mucosa covering the large intestine, plays a key role in viral entry by binding SARS-CoV-2's spike protein via heparan sulfate (HS). Here, using metabolic task analysis of multiple large microbiome sequencing data sets of the human gut microbiome, we identify a key commensal human intestinal bacteria capable of grooming glycocalyx HS and modulating SARS-CoV-2 infectivity in vitro. Moreover, we engineered the common probiotic Escherichia coli Nissle 1917 (EcN) to effectively block SARS-CoV-2 binding and infection of human cell cultures. Understanding these microbial interactions could lead to better risk assessments and novel therapies targeting viral entry mechanisms.}, }
@article {pmid39994360, year = {2025}, author = {Kurt, KC and Kurt, H and Tokuç, E and Özbey, D and Arabacı, DN and Aydın, S and Gönüllü, N and Skurnik, M and Tokman, HB}, title = {Isolation and characterization of new lytic bacteriophage PSA-KC1 against Pseudomonas aeruginosa isolates from cystic fibrosis patients.}, journal = {Scientific reports}, volume = {15}, number = {1}, pages = {6551}, pmid = {39994360}, issn = {2045-2322}, support = {IUC-BAP 34517//Istanbul University-Cerrahpasa, BAP/ ; }, mesh = {*Pseudomonas aeruginosa/virology/isolation &amp; purification/genetics ; Humans ; *Cystic Fibrosis/microbiology ; *Genome, Viral ; *Pseudomonas Infections/microbiology ; Pseudomonas Phages/genetics/isolation &amp; purification ; Bacteriophages/isolation &amp; purification/genetics/physiology ; Drug Resistance, Multiple, Bacterial/genetics ; }, abstract = {A novel lytic bacteriophage, PSA-KC1, was isolated from wastewater. In this study, the whole genome of the bacteriophage PSA-KC1 was analyzed, and its lytic properties were assessed. PSA-KC1 has a linear double-stranded DNA genome with a total length of 43,237 base pairs and a GC content of 53.6%. In total, 65 genes were predicted, 46 of which were assigned functions as structural proteins involved in genome replication, packaging or phage lysis. PSA-KC1 belongs to the genus Septimatrevirus under the Caudoviricetes class. The aim of this study was to investigate the efficacy of the lytic bacteriophage PSA-KC1 and compare it with that of the Pyophage phage cocktail on 25 multi drug resistant (MDR) Pseudomonas aeruginosa strains isolated from sputum samples of cystic fibrosis patients. Seventeen of these strains were susceptible (68%) to the PSA-KC1 lytic phage we isolated, whereas eight clinical strains were resistant. However, 22 (88%) of the P. aeruginosa strains were susceptible to the Pyophage cocktail, and three (12%) were resistant to the Phage cocktail. At the end of our study, a new lytic phage active against multidrug-resistant P. aeruginosa strains from CF patients was isolated, and its genome was characterized. Since the PSA-KC1 phage does not contain virulence factors, toxins or integrase genes, it can be expected to be a therapeutic candidate with the potential to be used safely in phage therapy.}, }
@article {pmid39994329, year = {2025}, author = {Abdelqader, EM and Mahmoud, WS and Gebreel, HM and Kamel, MM and Abu-Elghait, M}, title = {Correlation between gut microbiota dysbiosis, metabolic syndrome and breast cancer.}, journal = {Scientific reports}, volume = {15}, number = {1}, pages = {6652}, pmid = {39994329}, issn = {2045-2322}, mesh = {Humans ; Female ; *Metabolic Syndrome/microbiology ; *Gastrointestinal Microbiome ; *Breast Neoplasms/microbiology/epidemiology ; *Dysbiosis/microbiology ; Middle Aged ; Adult ; Feces/microbiology ; RNA, Ribosomal, 16S/genetics ; Case-Control Studies ; Bifidobacterium/isolation &amp; purification/genetics ; Lactobacillus/isolation &amp; purification/genetics ; Risk Factors ; }, abstract = {Breast cancer is a widespread cancer with a high death rate globally. The incidence of breast cancer is expected to increase, particularly in low and middle-income countries due to environmental factors and lifestyle changes. Several risk factors, such as age, family history, hormonal and reproductive factors, have been identified to influence breast cancer development. Metabolic syndrome, is a metabolic disorder that has also been linked to breast cancer risk. The gut microbiome has been suggested as one of the environmental factors leading to breast cancer. The human microbiome is mainly colonized in the intestine by various bacterial species, including Lactobacillus, Bifidobacterium, and Streptococcus and protect the host against pathogenic microorganisms and regulate the immune system. This study included 50 female breast cancer patients and 50 healthy controls with matched ages. Stool fresh samples were taken from test and control groups and stored at - 20 °C until further investigations. DNA of the bacteria in stool samples was extracted using reverse transcription-quantitative polymerase chain reaction to check for the bacterial 16s rRNA gene. The exclusion criteria included other malignancies, recent intestinal surgery, infectious diarrhea, prolonged use of antibiotics, substance addiction, and pregnancy or lactation. Our findings exhibited that breast cancer patients had a higher incidence of metabolic syndrome (60%) compared to cancer-free controls (40%). Furthermore, breast cancer patients had significantly lower Bifidobacterium and Lactobacillus counts than the controls. No significant difference was found in Streptococcus counts between groups. These findings support the relationship between breast cancer and metabolic syndrome and suggest the potential involvement of Lactobacillus and Bifidobacterium in breast cancer pathophysiology. Our study supports the relation between breast cancer and disorder of metabolic syndrome and suggests the potential involvement of Lactobacillus and Bifidobacterium in breast cancer pathophysiology. Further research is necessary to investigate the complex interactions between genes, the environment, and the gut microbiome in breast cancer development. Understanding these interactions could lead to the progress of novel strategies for breast cancer prevention and treatment.}, }
@article {pmid39992142, year = {2025}, author = {Sun, L and Wang, Q and Huang, J and Wang, H and Yu, Z}, title = {Disrupting the balance: how acne duration impacts skin microbiota assembly processes.}, journal = {Microbiology spectrum}, volume = {}, number = {}, pages = {e0260324}, doi = {10.1128/spectrum.02603-24}, pmid = {39992142}, issn = {2165-0497}, abstract = {Growing interest in the impact of microbial balance on health has driven studies on the ecological processes shaping the skin microbiota. Skin diseases, which alter the skin's local environment, can disrupt the microbial structure and interact with the disease itself. However, research on microbial assembly in diseased skin remains limited. In this study, we applied ecological models to characterize the processes shaping the skin microbiota in acne patients, considering the impact of disease duration on both skin pores and surfaces using bacterial amplicon sequencing. Our results revealed a significant shift in microbial diversity on the skin surface of patients with long-term acne. Further microbial community analyses showed a transition in ecological processes from healthy to diseased skin. Microbial communities on the skin surfaces of healthy controls and individuals with short-duration acne were primarily driven by heterogeneous selection, whereas microbial drift dominated the assembly process in the long-duration groups. Using the Sloan neutral model, we classified amplicon sequence variants (ASVs) into high-effect and low-effect groups based on relative abundance and sample occurrence. High-effect ASVs, likely exerting a greater ecological influence, were predominantly represented by Cutibacterium across all acne-affected skin groups, while Staphylococcus became enriched among high-effect ASVs in patients with long-term acne. Functional profiling further demonstrated that high-effect ASVs were significantly enriched in motility-related pathways. Additionally, we observed a reduction in microbial network complexity on skin surfaces as disease duration increased. Overall, the ecological dynamics of skin microbial communities may offer valuable insights into the mechanisms underlying disease onset and persistence.IMPORTANCEThe skin microbiota plays a critical role in acne development, yet the processes governing microbial assembly during acne progression remain poorly understood. Previous studies predominantly focused on factors such as acne severity, location, and duration in relation to skin microbial structure, with little attention given to the ecological mechanisms shaping the communities. In this study, we applied ecological models to investigate the processes influencing microbial assembly of skin microbiota in acne patients with varying disease durations and examined functions of ecologically important non-neutral amplicon sequence variants (ASVs). Our findings reveal a transition in ecological processes from deterministic to neutral processes as acne duration increased, with non-neutral ASVs potentially contributing to acne pathogenicity and persistence. These insights contribute to a deeper understanding of the ecological dynamics underlying acne and indicate that targeting these non-neutral ASVs or their associated functions may serve as the basis for future therapeutic strategies.}, }
@article {pmid39990405, year = {2025}, author = {Thinnes, CC and Waschkowitz, R and Courtney, E and Culligan, E and Fahy, K and Ferrazza, RAM and Ferris, C and Lagali, A and Lane, R and Maye, C and Murphy, O and Noone, D and Ryan, S and Bet, M and Corr, MC and Cummins, H and Hackett, D and Healy, E and Kulczycka, N and Lang, N and Madden, L and McHugh, L and Pyne, I and Varley, C and Harkin, N and Meade, R and O'Donnell, G and Nap, B and Martinelli, F and Heinken, A and Thiele, I}, title = {The MicroMap is a network visualisation resource for microbiome metabolism.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2025.02.13.637616}, pmid = {39990405}, issn = {2692-8205}, abstract = {The human microbiome plays a crucial role in metabolism and thereby influences health and disease. Constraint-based reconstruction and analysis (COBRA) has proven an attractive framework to generate mechanism-derived hypotheses along the nutrition-host-microbiome-disease axis within the computational systems biology community. Unlike for human, no large-scale visualisation resource for microbiome metabolism has been available to date. To address this gap, we created the MicroMap, a manually curated microbiome metabolic network visualisation, which captures the metabolic content of over a quarter million microbial genome-scale metabolic reconstructions. The MicroMap contains 5,064 unique reactions and 3,499 unique metabolites, including for 98 drugs. The MicroMap allows users to intuitively explore microbiome metabolism, inspect microbial metabolic capabilities, and visualise computational modelling results. Further, the MicroMap shall serve as an educational tool to make microbiome metabolism accessible to broader audiences beyond computational modellers. For example, we utilised the MicroMap to generate a comprehensive collection of 257,429 visualisations, corresponding to the entire scope of our current microbiome reconstruction resources, to enable users to visually compare and contrast the metabolic capabilities for different microbes. The MicroMap seamlessly integrates with the Virtual Metabolic Human (VMH, www.vmh.life) and the COBRA Toolbox (opencobra.github.io), and is freely accessible at the MicroMap dataverse (https://dataverse.harvard.edu/dataverse/micromap), in addition to all the generated reconstruction visualisations.}, }
@article {pmid39983320, year = {2025}, author = {Yu, D and Wang, T and Zhang, L and Gao, N and Huang, Y and Zhang, J and Yan, J}, title = {Identification of body fluid sources based on microbiome antibiotic resistance genes using high-throughput qPCR.}, journal = {Forensic science international. Genetics}, volume = {77}, number = {}, pages = {103241}, doi = {10.1016/j.fsigen.2025.103241}, pmid = {39983320}, issn = {1878-0326}, abstract = {Identifying the origin of body fluids is a critical step in forensic investigation. Recently, the development of high-throughput sequencing technology has led to the use of microbiomes for body fluid identification in forensic studies. However, high-throughput sequencing data are difficult to analyze, the sequencing protocol is complicated. An increasing number of studies have focused on antibiotic resistance genes (ARGs) in the human microbiome. The abundance and diversity of ARGs in different parts of the human body can be detected using quantitative polymerase chain reaction (qPCR). To date, no studies have inferred the sources of body fluids based on ARGs. Therefore, we attempted to use ARGs as a tool to infer the origin of body fluids. We assessed the abundance and diversity of 64 ARGs in blood, semen, saliva, vaginal secretions (VS), nasal secretions (NS), and fecal samples using high-throughput qPCR. The results showed that ARGs were more diverse in fecal samples, which was significantly higher than those of other sample types (P < 0.05). Principal coordinate analysis (PCoA) showed that the samples clustered mainly according to their type. We constructed a random forest classification model based on 64 ARGs with a prediction accuracy of 92.68 %. Next, we evaluated the importance of the features in the random forest model (mean decrease accuracy, MDA). Subsequently, we constructed prediction models for the top 40 and 20 ARGs after sorting genes with the highest MDA, and their prediction accuracies were both 92.68 %. The accuracy of the top 10 ARGs was 87.80 %. Notably, when only the top 10 characterized ARGs were used to construct models for saliva, semen, and VS samples, the prediction accuracy reached was 95.24 %. This shows that blood, semen, saliva, NS, VS, and fecal samples can be accurately identified using ARGs. Our results suggest that ARGs are promising markers for forensic body fluid identification.}, }
@article {pmid39980568, year = {2025}, author = {Davis, T and Decker, KT and Hosseini, D and Jameson, G and Borazanci, E}, title = {Skin microbiome differences in pancreatic adenocarcinoma, other cancers, and healthy controls: a pilot study.}, journal = {Frontiers in oncology}, volume = {15}, number = {}, pages = {1495500}, pmid = {39980568}, issn = {2234-943X}, abstract = {INTRODUCTION: Many studies have reported the importance of the human microbiome in relationship to the overall health of its host. While recent studies have explored the microbiome's role in various types of cancer compared to healthy patients, this pilot study is the first to investigate differences in the skin microbiome composition among pancreatic adenocarcinoma patients, individuals with other cancers, and cancer-free controls.<br><br>METHODS: The study characterizes the skin microbiome's potential associations with cancer status by analyzing skin swabs from the forehead and cheek of 58 participants using Next Generation Sequencing (NGS), differential abundance analysis, and machine learning techniques.<br><br>RESULTS: The study results indicated that the cancer group displayed a significantly higher mean alpha diversity compared to the control group. Additionally, a machine learning classification model achieved a mean F1 Score of 0.943 in predicting cancer status, indicating measurable differentiation in the skin microbiome between the study groups. This differentiation is supported by differential abundance methods, including ANCOM-BC and MaAsLin2.<br><br>DISCUSSION: This pilot study suggests that skin microbiome profiling could serve as a non-invasive biomarker for cancer detection and monitoring, which warrants a larger, longitudinal study to validate these results.}, }
@article {pmid39830242, year = {2025}, author = {Carter, MM and Zeng, X and Ward, CP and Landry, M and Perelman, D and Hennings, T and Meng, X and Weakley, AM and Cabrera, AV and Robinson, JL and Nguyen, T and Higginbottom, S and Maecker, HT and Sonnenburg, ED and Fischbach, MA and Gardner, CD and Sonnenburg, JL}, title = {A gut pathobiont regulates circulating glycine and host metabolism in a twin study comparing vegan and omnivorous diets.}, journal = {medRxiv : the preprint server for health sciences}, volume = {}, number = {}, pages = {}, pmid = {39830242}, abstract = {Metabolic diseases including type 2 diabetes and obesity pose a significant global health burden. Plant-based diets, including vegan diets, are linked to favorable metabolic outcomes, yet the underlying mechanisms remain unclear. In a randomized trial involving 21 pairs of identical twins, we investigated the effects of vegan and omnivorous diets on the host metabolome, immune system, and gut microbiome. Vegan diets induced significant shifts in serum and stool metabolomes, cytokine profiles, and gut microbial composition. Despite lower dietary glycine intake, vegan diet subjects exhibited elevated serum glycine levels linked to reduced abundance of the gut pathobiont Bilophila wadsworthia. Functional studies demonstrated that B. wadsworthia metabolizes glycine via the glycine reductase pathway and modulates host glycine availability. Removing B. wadsworthia from a complex microbiota in mice elevated glycine levels and improved metabolic markers. These findings reveal a previously underappreciated mechanism by which diet regulates host metabolic status via the gut microbiota.}, }
@article {pmid39979818, year = {2025}, author = {Li, W and Yang, J}, title = {Investigating the Anna Karenina principle of the breast microbiome.}, journal = {BMC microbiology}, volume = {25}, number = {1}, pages = {81}, pmid = {39979818}, issn = {1471-2180}, support = {202203021222244//Basic Research Program of Shanxi Province/ ; TYSGJ202201//Critical Talent Workstation Project/ ; 202105AC160030//Top Experts training Project for the Academy and Technology in Yunnan province/ ; XDYC-MY-2022-0005//Famous doctor project of Xingdian talent plan in Yunnan province/ ; 202201AY070001-232//The Scientific Research Fund of Yunnan province of China, Kunming Medical University Joint Research Project/ ; 2024EKKFKT-03//Neonatal Key Specialty of Yunnan province/ ; L-2024015//Yunnan health training project of high level talents/ ; }, abstract = {The relationship between the microbiome and disease has long been a central focus of research in human microbiome. Inspired by Leo Tolstoy's dictum, the Anna Karenina Principle (AKP) offers a framework for understanding the complex dynamics of microbial communities in response to perturbations, suggesting that dysbiotic individuals exhibit greater variability/heterogeneity in their microbiome compared to healthy counterparts. While some studies have proved the alignment of microbiome responses to disease with the AKP effect, it remains uncertain whether the human breast microbiome responds similarly to breast disease. This study used beta-diversity and similarity in Hill numbers, along with shared species analysis (SSA), to explore this issue. We observed that during mastitis, changes in both the taxa richness and composition in the breast milk microbiome align with the AKP effect, while alterations in abundant taxa exhibit an anti-AKP effect. The response of breast tissue microbiome to breast cancer differs from that of milk microbiome to mastitis. Breast cancer induce anti-AKP effects in taxa richness, and non-AKP effects in common taxa and taxa composition. Overall, our findings identified different responses to breast diseases across taxa abundance in the breast microbiome. Mastitis primarily involves increasing the heterogeneity of rare taxa in the breast milk microbiome, while breast cancer associates with decreased dispersion of rare taxa in the tissue microbiome.}, }
@article {pmid39977268, year = {2025}, author = {Zhang, Q and Cui, K and Kong, Y and Yu, J and Luo, Z and Yang, X and Gong, L and Xie, Y and Lin, J and Liu, C and Zhang, Z and Liu, Y and Liu, B and Liang, D and Zeng, W and He, Z and Lan, P}, title = {Targeting both the enzymatic and non-enzymatic functions of DHODH as a therapeutic vulnerability in c-Myc-driven cancer.}, journal = {Cell reports}, volume = {44}, number = {3}, pages = {115327}, doi = {10.1016/j.celrep.2025.115327}, pmid = {39977268}, issn = {2211-1247}, abstract = {c-Myc (Myc)-driven cancers exhibit aggressive phenotypes and therapeutic resistance. Here, integrating CRISPR-Cas9 screening, we identify dihydroorotate dehydrogenase (DHODH) as a promising target in Myc-driven cancer. Mechanistically, DHODH interacts with Myc to stabilize it independently of its enzymatic activity, thereby antagonizing SKP2-mediated polyubiquitination and proteasomal degradation. EN4, a Myc transcriptional activity inhibitor, disrupts DHODH-Myc interaction, promoting Myc degradation via SKP2. Additionally, Myc transcriptionally activates DHODH, enhancing pyrimidine biosynthesis and ferroptosis defense, processes dependent on DHODH enzymatic activity. Clinically, DHODH positively correlates with Myc, activating pyrimidine metabolism and ferroptosis defense in Myc-driven cancers. Hyperactivation of the DHODH-Myc axis is linked to colorectal cancer progression and poor prognosis. Therapeutically, combining EN4 with a DHODH enzymatic inhibitor demonstrates potent antitumor efficacy in Myc-driven colorectal cancer. Overall, our findings elucidate the metabolic and non-metabolic roles of DHODH in Myc-driven cancer, underscoring its dual potential as a therapeutic target addressing both enzymatic and non-enzymatic functions.}, }
@article {pmid39972069, year = {2025}, author = {Höyhtyä, M and Haaramo, A and Nikkonen, A and Ventin-Holmberg, R and Agrawal, N and Ritari, J and Hickman, B and Partanen, J and Alapulli, H and Tuokkola, J and Salonen, A and de Vos, WM and Kolho, KL}, title = {Fecal microbiota and genetics in pediatric-onset orofacial granulomatosis and Crohn´s disease.}, journal = {Scientific reports}, volume = {15}, number = {1}, pages = {6020}, pmid = {39972069}, issn = {2045-2322}, support = {TYH2016224//Helsingin ja Uudenmaan Sairaanhoitopiiri/ ; }, mesh = {Humans ; *Crohn Disease/microbiology/genetics ; *Granulomatosis, Orofacial/genetics/microbiology ; *Feces/microbiology ; Male ; Female ; Child ; Adolescent ; Nod2 Signaling Adaptor Protein/genetics ; Case-Control Studies ; Gastrointestinal Microbiome/genetics ; Leukocyte L1 Antigen Complex/genetics ; Saliva/microbiology ; }, abstract = {Orofacial granulomatosis (OFG) is a rare chronic inflammatory condition. It is under debate, whether it is a condition of its own or merely a subtype of Crohn's disease (CD). We aimed to search for markers characteristic of patients with pediatric-onset OFG compared to patients with pediatric-onset CD. We recruited young patients with OFG (with or without CD, n = 29), CD (n = 24), and healthy controls (n = 20). All participants provided a fecal sample for microbiota and calprotectin analyses and saliva for DNA analysis of genes associated with OFG and kept a 3-day food diary. Oral disease activity was evaluated using The Oral Disease Activity Score by an otorhinolaryngologist and a dentist. We observed decreased relative abundance in class Clostridia and increased relative abundances of classes Actinobacteria and Bacilli in the feces of patients with OFG when compared to patients with CD and healthy controls. The relative abundances of Bifidobacterium adolescentis increased and Faecalibacterium prausnitzii decreased along with the increase in the Oral Disease Activity Score. We found the NOD2 gene rs8057341 allele A to be enriched in patients with OFG compared to patients with CD. These findings support the theory that OFG is a distinct disease phenotype.}, }
@article {pmid39971547, year = {2025}, author = {Lan, P and He, XS and Zhang, ZJ and Zhang, B}, title = {[Critical issues in surgical treatment for colorectal cancer].}, journal = {Zhonghua wei chang wai ke za zhi = Chinese journal of gastrointestinal surgery}, volume = {28}, number = {1}, pages = {21-27}, doi = {10.3760/cma.j.cn441530-20250106-00010}, pmid = {39971547}, issn = {1671-0274}, support = {2022YFA1304000//National Key R&amp;D Program of China/ ; U21A20344//National Natural Science Foundation of China/ ; }, mesh = {Humans ; *Colorectal Neoplasms/surgery ; China ; Neoplasm Staging ; Evidence-Based Medicine ; }, abstract = {Clinical research on colorectal cancer in China has developed rapidly in recent years. Based on evidence-based medicine, the Chinese Colorectal Cancer Diagnosis and Treatment Standards and the CSCO Guidelines for Colorectal Cancer are continuously updated, which have been instrumental in optimizing the full-process management of colorectal cancer and improving cancer outcomes. While significant progress has been made, we must remain aware that there are still many urgent and key issues to be solved in the field of surgical treatment e.g. sphincter-preserving strategies, surgical approaches, management of T1 stage tumors, and surgical treatment for metastatic colorectal cancer. In the future, more high-quality, original research from China will be needed to address these challenges, standardize surgical approaches, and improve treatment effect.}, }
@article {pmid39971202, year = {2025}, author = {Li, T and Wu, X and Li, X and Chen, M}, title = {Cancer-associated fungi: An emerging powerful player in cancer immunotherapy.}, journal = {Biochimica et biophysica acta. Reviews on cancer}, volume = {}, number = {}, pages = {189287}, doi = {10.1016/j.bbcan.2025.189287}, pmid = {39971202}, issn = {1879-2561}, abstract = {The role of the human microbiome in cancer has been extensively studied, focusing mainly on bacteria-host interactions and their impact on tumor development and treatment response. However, fungi, an immune-active component of the human microbiome, have received less attention regarding their roles in cancer. Recent studies have identified the widespread and specific colonization and distribution of fungi in multiple sites in patients across various cancer types. Importantly, host-fungal immune interactions significantly influence immune regulation within the tumor microenvironment. The rapid advancement of immune-checkpoint blockade (ICB)-based cancer immunotherapy creates an urgent need for effective biomarkers and synergistic therapeutic targets. Cancer-associated fungi and their associated antifungal immunity demonstrate significant potential and efficacy in enhancing cancer immunotherapy. This review summarizes and discusses the growing evidence of the functions and mechanisms of commensal and pathogenic cancer-associated fungi in cancer immunotherapy. Additionally, we emphasize the potential of fungi as predictive biomarkers and therapeutic targets in cancer immunotherapy.}, }
@article {pmid39966419, year = {2025}, author = {Heidrich, V and Fackelmann, G and Malesevic, M and Armanini, F and Dey, H and Mengoni, C and Stanisavljevic, N and Vukotic, G and Segata, N}, title = {Newly identified species from the dog dental plaque microbiome highlight little overlap with humans.}, journal = {NPJ biofilms and microbiomes}, volume = {11}, number = {1}, pages = {30}, pmid = {39966419}, issn = {2055-5008}, abstract = {Understudied pet-associated microbiomes represent a rich source for the discovery of microbial taxa important for pet and human health. From a cohort of 23 dogs, we sampled and metagenomically sequenced 64 dental plaque microbiomes, generating 1945 metagenome-assembled genomes spanning 347 microbial species, including 277 undercharacterized species without cultivated representatives. Integration with human microbiome data revealed the dog plaque microbiome is more diverse than - and shows little overlap (5.9% species in common) with - the human plaque microbiome, even though some shared periodontal pathobionts arise as a potential concern.}, }
@article {pmid39966341, year = {2025}, author = {Qin, L and Sun, T and Li, X and Zhao, S and Liu, Z and Zhang, C and Jin, C and Xu, Y and Gao, X and Cao, Y and Wang, J and Han, T and Yan, L and Song, J and Zhang, F and Liu, F and Zhang, Y and Huang, Y and Song, Y and Liu, Y and Zhang, J and Zhang, X and Yao, Z and Chen, H and Zhang, Z and Zhao, S and Feng, Y and Zhang, YN and Yu, Q and Cao, F and Zhao, L and Xie, L and Geng, L and Feng, Q and Zhao, H and Chen, ZJ}, title = {Population-level analyses identify host and environmental variables influencing the vaginal microbiome.}, journal = {Signal transduction and targeted therapy}, volume = {10}, number = {1}, pages = {64}, pmid = {39966341}, issn = {2059-3635}, mesh = {Female ; Humans ; *Vagina/microbiology ; *Microbiota/genetics ; Adult ; Middle Aged ; *RNA, Ribosomal, 16S/genetics ; Cross-Sectional Studies ; Vaginosis, Bacterial/microbiology/genetics ; Lactobacillus/genetics ; China ; }, abstract = {The vaginal microbiome is critical for the reproductive health of women, yet the differential impacts exerted by the host and by ambient environmental variables on the vaginal microbiome remain largely unknown. Here, we conducted a comprehensive cross-sectional study of the relationships between the vaginal microbiome and 81 matched host and environmental variables across 6755 Chinese women. By 16S rRNA sequencing, we identified four core vaginal microbiota with a prevalence of over 90% and a total median abundance of 98.8%. Twenty-four variables, including physiology, lifestyle behaviors, gynecologic history, social and environmental information, were found associated with the microbiome composition, of which bacterial vaginosis (BV) showed the largest effect size. Age was among the strongest explanatory variables and the vaginal microbiome dynamically succeeded with increasing age, especially with a composition turning point at the age of 45. Our mediation analyses indicated that the effects of age on the microbiome could be mediated by variables such as parity number and lifestyles. We further classified the vaginal microbiomes of the population into 13 "Vagitypes". Women with Lactobacillus iners- and Lactobacillus jensenii-dominated Vagitypes had significantly higher live birth rate than those with Vagitype dominated by Fannyhessea vaginae (53.40%, 59.09% vs 21.43%; OR [95% CI]: 3.62 [1.12-14.87], 5.39 [1.27-27.36]; P = 0.031, P = 0.021). This study provides a comprehensive overview of the associations between identified variables and the vaginal microbiome, representing an important step toward understanding of environment-microbe-host interactions.}, }
@article {pmid39956340, year = {2025}, author = {Sharma, M and Pudlo, N and Järvå, MA and Kaur, A and John, A and Burchill, L and Lingford, JP and Epa, R and Abayakoon, P and Scott, NE and Turkenburg, JP and Davies, GJ and Martens, EC and Goddard-Borger, ED and Williams, SJ}, title = {Sulfoglycolysis sustains Eubacterium rectale in low-fiber diets.}, journal = {The Journal of biological chemistry}, volume = {}, number = {}, pages = {108320}, doi = {10.1016/j.jbc.2025.108320}, pmid = {39956340}, issn = {1083-351X}, abstract = {The production of short-chain fatty acids (SCFAs) by Firmicutes (Bacillota) within the human gastrointestinal tract is recognized as critical for gut health and the progression of a range of disease states. Firmicutes are the most diverse phylum of human gut bacteria and are highly studied, and are often specialized to degrade just a few polysaccharide substrates. Members of the Firmicutes include key bacteria that produce butyrate, an SCFA that is generally not produced by members of the other major phyla. Recently, it was shown that Eubacterium rectale, a widespread member of the Firmicutes belonging to the Clostridiales cluster XIVa, can grow on the unusual but ubiquitous plant-derived sugar SQ using a sulfoglycolytic sulfofructose transaldolase pathway. Here, we show that in addition to SQ, E. rectale can also grow on the SQ glycoside sulfoquinovosyl glycerol (SQGro). The 3D structure of the E. rectale sulfoquinovosidase (SftG) shares strong structural conservation with other carbohydrate active enzyme family GH31 SQases. Using sequence-similarity networks, we provide new biological context to a conserved domain of unknown function protein SftX belonging to DUF4867, which is conserved in the sulfoglycolytic sulfofructose transaldolase pathway, and determine its 3D structure. Finally, with the aid of a synthetic mini-human microbiome reconstituted in germ-free mice, we show that an SQ dietary supplement can rescue E. rectale from population crashes that occur upon switching from a high-fiber to a low-fiber, high-fat diet. This suggests that SQ or SQGro has potential as a prebiotic for promoting the maintenance of this important butyrate-producing bacterium within the colonic microbiota.}, }
@article {pmid39956335, year = {2025}, author = {Abreu, MT and Devkota, S and Issokson, K}, title = {A Mediterranean diet for Crohn's disease: Embracing colorful diversity to improve the microbiome.}, journal = {Gastroenterology}, volume = {}, number = {}, pages = {}, doi = {10.1053/j.gastro.2025.02.003}, pmid = {39956335}, issn = {1528-0012}, }
@article {pmid39955481, year = {2025}, author = {Wan, Y and Pike, R and Harley, A and Mumin, Z and Potterill, I and Meunier, D and Ganner, M and Getino, M and Coelho, J and Jauneikaite, E and Moganeradj, K and Brown, CS and Holmes, AH and Demirjian, A and Hopkins, KL and Pichon, B}, title = {Complete genome assemblies and antibiograms of 22 Staphylococcus capitis isolates.}, journal = {BMC genomic data}, volume = {26}, number = {1}, pages = {12}, pmid = {39955481}, issn = {2730-6844}, support = {PSN109/WT_/Wellcome Trust/United Kingdom ; NIHR200876//National Institute for Health and Care Research/ ; UGG10057//Price David Evans endowment/ ; }, mesh = {*Staphylococcus capitis/genetics/drug effects/isolation &amp; purification ; *Microbial Sensitivity Tests ; *Genome, Bacterial/genetics ; *Anti-Bacterial Agents/pharmacology ; Humans ; Whole Genome Sequencing ; Staphylococcal Infections/microbiology/drug therapy ; Drug Resistance, Multiple, Bacterial/genetics ; }, abstract = {OBJECTIVE: Staphylococcus capitis is part of the human microbiome and an opportunistic pathogen known to cause catheter-associated bacteraemia, prosthetic joint infections, skin and wound infections, among others. Detection of S. capitis in normally sterile body sites saw an increase over the last decade in England, where a multidrug-resistant clone, NRCS-A, was widely identified in blood samples from infants in neonatal intensive care units. To address a lack of complete genomes and antibiograms of S. capitis in public databases, we performed long- and short-read whole-genome sequencing, hybrid genome assembly, and antimicrobial susceptibility testing of 22 diverse isolates.<br><br>DATA DESCRIPTION: We present complete genome assemblies of two S. capitis type strains (subspecies capitis: DSM 20326; subspecies urealyticus: DSM 6717) and 20 clinical isolates (NRCS-A: 10) from England. Each genome is accompanied by minimum inhibitory concentrations of 13 antimicrobials including vancomycin, teicoplanin, daptomycin, linezolid, and clindamycin. These 22 genomes were 2.4-2.7 Mbp in length and had a GC content of 33%. Plasmids were identified in 20 isolates. Resistance to teicoplanin, daptomycin, gentamicin, fusidic acid, rifampicin, ciprofloxacin, clindamycin, and erythromycin was seen in 1-10 isolates. Our data are a resource for future studies on genomics, evolution, and antimicrobial resistance of S. capitis.}, }
@article {pmid39952625, year = {2025}, author = {Javanshir, N and Ebrahimi, V and Mazhari, Z and Saedaei, B and Zuo, T and Fard, NA}, title = {The antiviral effects and underlying mechanisms of probiotics on viral infections.}, journal = {Microbial pathogenesis}, volume = {}, number = {}, pages = {107377}, doi = {10.1016/j.micpath.2025.107377}, pmid = {39952625}, issn = {1096-1208}, abstract = {In public health emergencies, viral diseases like influenza and COVID-19 have become a major concern. One of the proposed responses to this concern is the use of probiotics. Probiotics have a potent role in arming our bodies to combat viral infections. They affect the innate and adaptive immune systems in various ways. Accumulating studies has shown that probiotics can reduce the possibility of infection or the duration of respiratory symptoms by modulating the functions of the immune system. This review aims to summarize the impacts of probiotics on respiratory viral infections and their potential antiviral mechanisms. Therefore, we herein discussed probiotics in relation to lung immunity, distinct types of respiratory viral infections (VRIs), including influenza, rhinoviruses, respiratory syncytial virus, and upper respiratory viral infections, and lastly, probiotics and their effects on COVID-19. However, more studies are needed to explore the antiviral mechanisms of probiotics.}, }
@article {pmid39949350, year = {2024}, author = {Lee, DB and Hwang, IS}, title = {Macronutrient balance determines the human gut microbiome eubiosis: insights from in vitro gastrointestinal digestion and fermentation of eight pulse species.}, journal = {Frontiers in microbiology}, volume = {15}, number = {}, pages = {1512217}, pmid = {39949350}, issn = {1664-302X}, abstract = {The interactions between macronutrients, the human gut microbiome, and their metabolites (short-chain fatty acids) were comprehensively investigated via an in vitro digestion and fermentation model subjected to eight pulse species. 16S rRNA sequencing and taxonomic analysis of pulse digesta fermented for up to 24 h revealed an increase in the relative abundance of gut health-detrimental genera represented by Escherichia-Shigella in kidney bean, soybean, cowpea, chickpea, and black bean samples. In contrast, the relative abundance of health-positive genera, including Bacteroides, Eubacterium, and Akkermansia, was elevated in red bean, mung bean, and Heunguseul. At the same time, the proportion of the pathogenic Escherichia-Shigella decreased. Concurrently, these three species exhibited an increase in microbial diversity as evidenced by the calculation of α-diversity (Shannon index) and β-diversity (Bray-Curtis distance). Despite the lower nutrient contents in the three pulses, represented by carbohydrates, amino acids, and fatty acids, network analysis revealed that the nutrient contents in the pulse digesta possess complex positive or negative correlations with a variety of bacteria, as well as their metabolites. These correlations were more pronounced in red bean, mung bean, and Heunguseul than in the other pulses. It was postulated that the overall potential to nourish gut environments in these species was due to the balance of their nutritional components. The linear regression analysis demonstrated that there was a negative association between carbohydrate and amino acid contents and the increase in Shannon indices. Furthermore, the ratio of carbohydrates to fatty acids and amino acids to fatty acids displayed negative correlations with the diversity increase. The ratio of carbohydrates to amino acids showed a weak positive correlation. It is noteworthy that a diet comprising foods with a balanced nutritional profile supports the growth of beneficial gut microbes, thereby promoting microbial eubiosis. Consistent work on different ingredients is essential for precise insight into the interplay between food and the human microbiome in complex dietary patterns.}, }
@article {pmid39947133, year = {2025}, author = {Elmassry, MM and Sugihara, K and Chankhamjon, P and Kim, Y and Camacho, FR and Wang, S and Sugimoto, Y and Chatterjee, S and Chen, LA and Kamada, N and Donia, MS}, title = {A meta-analysis of the gut microbiome in inflammatory bowel disease patients identifies disease-associated small molecules.}, journal = {Cell host &amp; microbe}, volume = {33}, number = {2}, pages = {218-234.e12}, doi = {10.1016/j.chom.2025.01.002}, pmid = {39947133}, issn = {1934-6069}, mesh = {*Gastrointestinal Microbiome ; Humans ; Mice ; Animals ; *Inflammatory Bowel Diseases/microbiology ; Feces/microbiology ; Crohn Disease/microbiology ; Disease Models, Animal ; Multigene Family ; Colitis/microbiology ; Metagenomics ; Clostridium/genetics ; Mice, Inbred C57BL ; Female ; }, abstract = {Gut microbiome changes have been associated with several human diseases, but the molecular and functional details underlying these associations remain largely unknown. Here, we performed a meta-analysis of small molecule biosynthetic gene clusters (BGCs) in metagenomic samples of the gut microbiome from inflammatory bowel disease (IBD) patients and matched healthy subjects and identified two Clostridia-derived BGCs that are significantly associated with Crohn's disease (CD), a main IBD type. Using synthetic biology, we discovered and solved the structures of six fatty acid amides as the products of the CD-enriched BGCs, which we subsequently detected in fecal samples from IBD patients. Finally, we show that the discovered molecules disrupt gut permeability and exacerbate disease in chemically or genetically susceptible mouse models of colitis. These findings suggest that microbiome-derived small molecules may play a role in the etiology of IBD and represent a generalizable approach for discovering molecular mediators of disease-relevant microbiome-host interactions.}, }
@article {pmid39947073, year = {2025}, author = {Cotugno, N and Sanna, M and Amodio, D and Morrocchi, E and Pighi, C and Medri, C and Pascucci, GR and Santilli, V and Manno, EC and Zangari, P and Rossetti, C and Colantoni, N and Olivieri, G and Emili, E and Neri, A and Rotili, A and Rossi, P and Levy, O and Putignani, L and Palma, P and , }, title = {Pre-vaccination immune markers predict response to BNT162b2 mRNA vaccine in vulnerable groups - The CONVERS project, report from a pediatric tertiary hospital.}, journal = {Vaccine}, volume = {49}, number = {}, pages = {126778}, doi = {10.1016/j.vaccine.2025.126778}, pmid = {39947073}, issn = {1873-2518}, abstract = {BACKGROUND: Whereas several studies have demonstrated the long-term immunogenicity of BNT162b2 vaccine in healthy adults, little evidence was provided in vulnerable populations (VPs) with generally low ability to respond to immunizations. We aimed to identify pre-vaccination immune phenotype and transcriptional signatures in B and T-cell subsets associated with immune response and long-term maintenance upon SARS-CoV-2 vaccination in VPs.<br><br>METHODS: A cohort of VPs (N&#xa0;=&#xa0;169) including solid organ transplant recipients (SOT; N&#xa0;=&#xa0;35), Inflammatory Bowel Disease (N&#xa0;=&#xa0;31), Down Syndrome (N&#xa0;=&#xa0;42), people living with HIV (N&#xa0;=&#xa0;36), primary immune deficiencies (N&#xa0;=&#xa0;25) and healthy controls (N&#xa0;=&#xa0;37) were enrolled in the CONVERS Study. SARS-CoV-2 Vaccine responsiveness was evaluated by SARS-CoV-2-specific Ab and SARS-CoV-2-specific CD4+ T cells in VPs naive to infection or vaccination. Based on the humoral response at T28, individuals were classified as Protected (P: anti-spike antibody [anti-S] titer &#x2265;0.8) and Not-Protected (NP: anti-S titer <0.8). Peripheral blood mononuclear cells, after SARS-CoV-2 Prot-S peptides stimulation were sort-purified in four cell subsets and analyzed by multiplexed RT-PCR (Fluidigm, Biomark).<br><br>RESULTS: SOT presented a significantly lower serological immunogenicity with 31&#xa0;% of individuals being NP at T28 whereas only 1 out of the remaining 119 resulted Ab negative at T28. At T0, NP individuals showed a lower increase of Ag specific CD40L+ T cells and lower switched memory B cells compared to P patients. Gene-expression analysis revealed distinct signatures at baseline between P and NP individuals with 63 and 49 DEGs identified in two experimental conditions, respectively unstimulated and stimulated.<br><br>CONCLUSIONS: Pre-vaccination B and T-cell characteristics at both phenotypic and gene- expression level correlate with short- and long- term memory maintenance in VPs with lower immunogenicity upon BNT162b2 vaccine. Such signatures need to be validated in larger cohorts and may provide a predictive score to inform personalized and more effective vaccine interventions.}, }
@article {pmid39940948, year = {2025}, author = {Rastegari, F and Driscoll, M and Riordan, JD and Nadeau, JH and Johnson, JS and Weinstock, GM}, title = {Comparison of Lysis and Amplification Methodologies for Optimal 16S rRNA Gene Profiling for Human and Mouse Microbiome Studies.}, journal = {International journal of molecular sciences}, volume = {26}, number = {3}, pages = {}, doi = {10.3390/ijms26031180}, pmid = {39940948}, issn = {1422-0067}, support = {HG01244/GF/NIH HHS/United States ; }, mesh = {*RNA, Ribosomal, 16S/genetics ; Humans ; Animals ; Mice ; *Microbiota/genetics ; *Feces/microbiology ; Bacteria/genetics/classification ; Polymerase Chain Reaction/methods ; DNA, Bacterial/genetics ; Sequence Analysis, DNA/methods ; }, abstract = {When conducting sequence-based analysis of microbiome samples, it is important to accurately represent the bacterial communities present. The aim of this study was to compare two commercially available DNA isolation and PCR amplification approaches to determine their impact on the taxonomic composition of microbiome samples following 16S rRNA gene sequencing. A well-established 16S rRNA gene profiling approach, which was widely used in the Human Microbiome Project (HMP), was compared with a novel alkaline degenerative technique that utilizes alkaline cell lysis in combination with a degenerate pool of primers for nucleic acid extraction and PCR amplification. When comparing these different approaches for the microbiome profiling of human and mouse fecal samples, we found that the alkaline-based method was able to detect greater taxonomic diversity. An in silico analysis of predicted primer binding against a curated 16S rRNA gene reference database further suggested that this novel approach had the potential to reduce population bias found with traditional methods, thereby offering opportunities for improved microbial community profiling.}, }
@article {pmid39939954, year = {2025}, author = {Swarup, S and Gupta, A and Chung, M and Radhakrishnan, V and Davis, V and Lynch, MDJ and Charles, TC and Cheng, J and Mendoza, G}, title = {Rapid shift of gut microbiome and enrichment of beneficial microbes during arhatic yoga meditation retreat in a single-arm pilot study.}, journal = {BMC complementary medicine and therapies}, volume = {25}, number = {1}, pages = {51}, pmid = {39939954}, issn = {2662-7671}, abstract = {BACKGROUND: The human microbiome plays a vital role in human health, mediated by the gut-brain axis, with a large diversity of functions and physiological benefits. The dynamics and mechanisms of meditations on oral and gut microbiome modulations are not well understood. This study investigates the short-term modulations of the gut and oral microbiome during an Arhatic Yoga meditation retreat as well as on the role of microbiome in improving well-being through a possible gut-brain axis.<br><br>METHODS: A single-arm pilot clinical trial was conducted in a controlled environment during a 9-day intensive retreat of Arhatic Yoga meditation practices with vegetarian diet. Oral and fecal samples of 24 practitioners were collected at the start (Day0: T1), middle (Day3: T2), and end (Day9:T3) of the retreat. Targeted 16S rRNA gene amplicon sequencing was performed for both oral and gut samples. Functional pathway predictions was identified using phylogenetic investigation of communities by reconstruction of unobserved states (PICRUSt2). DESeq2 was used to identify the differential abundant taxa. Various statistical analyses were performed to assess the significant changes in the data.<br><br>RESULTS: Our findings revealed that Arhatic Yoga meditation together with a vegetarian diet led to changes in the oral and gut microbiome profiles within the 9-day retreat. Oral microbiome profile showed a significant (p&#x2009;<&#x2009;0.05) difference in the species richness and evenness at the end of study, while non-metric multidimensional scaling (NMDS) confirmed the shift in the gut microbiome profile of the practitioners by T2 timepoint, which was further supported by PERMANOVA analysis (p&#x2009;<&#x2009;0.05). Health-benefiting microbes known to improve the gastrointestinal and gut-barrier functions, immune modulation, and gut-brain axis were enriched. Gut microbiome of both beginner and advanced Arhatic Yoga practitioners showed similar trends of convergence by the end of study. This implies a strong selection pressure by Arhatic Yoga meditation together with a vegetarian diet on the beneficial gut microbiome.<br><br>CONCLUSION: This pilot study demonstrates that Arhatic Yoga meditation practices combined with a vegetarian diet during a short intensive retreat resulted in enrichment of known health-promoting microbes. Such microbial consortia may be developed for potential health benefits and used as probiotics to improve the gastrointestinal and immune systems, as well as functions mediated by the gut-brain axis.<br><br>TRIAL REGISTRATION: Study was submitted in https://clinicaltrials.gov/on28-02-2024 . Retrospective registered.}, }
@article {pmid39932857, year = {2025}, author = {Lopetuso, LR and Deleu, S and Puca, P and Abreu, MT and Armuzzi, A and Barbara, G and Caprioli, F and Chieng, S and Costello, SP and Damiani, A and Danese, S and Del Chierico, F and D'Haens, G and Dotan, I and Facciotti, F and Falony, G and Fantini, MC and Fiorino, G and Gionchetti, P and Godny, L and Hart, A and Kupčinskas, J and Iqbal, T and Laterza, L and Lombardini, L and Maharshak, N and Marasco, G and Masucci, L and Papa, A and Paramsothy, S and Petito, V and Piovani, D and Pugliese, D and Putignani, L and Raes, J and Ribaldone, DG and Sanguinetti, M and Savarino, EV and Sokol, H and Vetrano, S and Ianiro, G and Cammarota, G and Cominelli, F and Pizarro, TT and Tilg, H and Gasbarrini, A and Vermeire, S and Scaldaferri, F}, title = {Guidance for Fecal Microbiota Transplantation Trials in Ulcerative Colitis: The Second ROME Consensus Conference.}, journal = {Inflammatory bowel diseases}, volume = {}, number = {}, pages = {}, doi = {10.1093/ibd/izaf013}, pmid = {39932857}, issn = {1536-4844}, support = {//European Crohn's and Colitis Organization/ ; //Crohn's &amp; Colitis Foundation: Clinical Research Investigator Initiated Award (CRIA)/ ; 882725//Senior Research Award (SRA)/ ; }, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) is emerging as a potential treatment modality for individuals living with inflammatory bowel disease (IBD). Despite its promise, the effectiveness of FMT for treating IBD, particularly for ulcerative colitis (UC), still requires thorough clinical investigation. Notwithstanding differences in methodologies, current studies demonstrate its potential for inducing remission in UC patients. Therefore, standardized and robust randomized clinical trials (RCTs) are needed to further support its efficacy for managing UC. The aim of the second Rome Consensus Conference was to address gaps and uncertainties identified in previous research regarding FMT and to offer a robust framework for future studies applied to the treatment of UC.<br><br>METHODS: Global experts in the field of clinical IBD, mucosal immunology, and microbiology (N&#x2005;=&#x2005;48) gathered to address the need for standardized clinical trials in FMT investigation. The group focused on key issues, such as stool donation, donor selection, characterization of fecal biomass, potential administration routes, as well as the process of induction, maintenance, and endpoint readouts.<br><br>RESULTS AND CONCLUSIONS: The consensus achieved during this conference established standardization of methods and protocols to enhance the current quality of research, with the aim of eventual implementation of FMT in managing UC and the ultimate goal of improving patient outcomes.}, }
@article {pmid39916516, year = {2025}, author = {Nunez, H and Nieto, PA and Mars, RA and Ghavami, M and Sew Hoy, C and Sukhum, K}, title = {Early life gut microbiome and its impact on childhood health and chronic conditions.}, journal = {Gut microbes}, volume = {17}, number = {1}, pages = {2463567}, pmid = {39916516}, issn = {1949-0984}, mesh = {Humans ; *Gastrointestinal Microbiome ; Chronic Disease ; Animals ; Infant ; Child Health ; Child, Preschool ; Bacteria/classification/genetics/isolation &amp; purification ; Infant, Newborn ; Feces/microbiology ; Child ; }, abstract = {The development of the gut microbiome is crucial to human health, particularly during the first three years of life. Given its role in immune development, disturbances in the establishment process of the gut microbiome may have long term consequences. This review summarizes evidence for these claims, highlighting compositional changes of the gut microbiome during this critical period of life as well as factors that affect gut microbiome development. Based on human and animal data, we conclude that the early-life microbiome is a determinant of long-term health, impacting physiological, metabolic, and immune processes. The early-life gut microbiome field faces challenges. Some of these challenges are technical, such as lack of standardized stool collection protocols, inconsistent DNA extraction methods, and outdated sequencing technologies. Other challenges are methodological: small sample sizes, lack of longitudinal studies, and poor control of confounding variables. To address these limitations, we advocate for more robust research methodologies to better understand the microbiome's role in health and disease. Improved methods will lead to more reliable microbiome studies and a deeper understanding of its impact on health outcomes.}, }
@article {pmid39930028, year = {2025}, author = {Rook, O and Zwart, H}, title = {Awareness of human microbiome may promote healthier lifestyle and more positive environmental attitudes.}, journal = {Communications medicine}, volume = {5}, number = {1}, pages = {39}, pmid = {39930028}, issn = {2730-664X}, support = {No 964590//EC | Horizon 2020 Framework Programme (EU Framework Programme for Research and Innovation H2020)/ ; No 964590//EC | Horizon 2020 Framework Programme (EU Framework Programme for Research and Innovation H2020)/ ; }, abstract = {BACKGROUND: The human microbiome is an essential factor of physical and mental health, yet the general population has little knowledge about it. This survey explores public familiarity with the human microbiome and (potential) public preferences related to monitoring and improving one's microbiome health. The study also examines whether recognizing the importance of one's microbiome may promote a more ecosystem-aware perspective towards microorganisms.<br><br>METHODS: We conducted an online survey with nationally representative samples from France, Germany, South Korea, and Taiwan (N&#x2009;=&#x2009;2860). The results were interpreted using descriptive statistics and network analysis. We also performed a t-test to compare perceptions of microorganisms before and after a short reflection on the role of human microbiome for one's body and health.<br><br>RESULTS: In our data, most respondents express willingness to monitor the health of their microbiome (especially, in the European countries) and to adjust their lifestyle such as diet and exercise to improve it. A paired samples t-test shows a slight positive shift in perceptions of microorganisms and the microbial world after the reflection exercise compared to baseline.<br><br>CONCLUSIONS: The study shows that the public recognize the essential role of the human microbiome in health and are willing to take care of it, which may have implications for public health policy. Our findings also suggest that stronger awareness of the human microbiome may promote lifestyle change and a more encompassing environmental outlook.}, }
@article {pmid39927868, year = {2025}, author = {Zouiouich, S and Wan, Y and Vogtmann, E and Porras, C and Abnet, CC and Shi, J and Sinha, R}, title = {Sample size estimations based on human microbiome temporal stability over six months: a shallow shotgun metagenome sequencing analysis.}, journal = {Cancer epidemiology, biomarkers &amp; prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology}, volume = {}, number = {}, pages = {}, doi = {10.1158/1055-9965.EPI-24-0839}, pmid = {39927868}, issn = {1538-7755}, abstract = {BACKGROUND: Biological factors impact the human microbiome, highlighting the need for reasonably estimating sample sizes in future population studies.<br><br>METHODS: We assessed the temporal stability of fecal microbiome diversity, species composition, and genes and functional pathways through shallow shotgun metagenome sequencing. Using intraclass correlation coefficients (ICC), we measured biological variability over six months. We estimated case numbers for 1:1 or 1:3 matched case-control studies, considering significance levels of 0.05 and 0.001 with 80% power, based on the collected fecal specimens per participant.<br><br>RESULTS: The fecal microbiome's temporal stability over six months varied (ICC <0.6) for most alpha and beta diversity metrics. Heterogeneity was seen in species, genes, and pathways stability (ICC 0.0-0.9). Detecting an odds ratio of 1.5 per standard deviation required 1,000-5,000 cases (0.05 significance for alpha and beta; 0.001 for species, genes, pathways) with equal cases and controls. Low-prevalent species needed 15,102 cases; high-prevalent species required 3,527. Similar needs applied to genes and pathways. In a 1:3 matched case-control study with one fecal specimen, 10,068 cases were needed for low-prevalent species; 2,351 for high-prevalent species. For odds ratios of 1.5 with multiple specimens, cases needed for low-prevalent species were 15,102 (one specimen), 8,267 (two specimens), and 5,989 (three specimens).<br><br>CONCLUSIONS: Detecting disease associations requires a large number of cases. Repeating prediagnostic samples and matching cases to more controls could decrease the needed number of cases for such detections.<br><br>IMPACT: Our results will help future epidemiologic studies design and implement well-powered microbiome studies.}, }
@article {pmid39927761, year = {2025}, author = {Frame, LA}, title = {Fiber, microbiomes, and SCFAs: insights from companion animal models to inform personalized nutrition.}, journal = {mSystems}, volume = {}, number = {}, pages = {e0145424}, doi = {10.1128/msystems.01454-24}, pmid = {39927761}, issn = {2379-5077}, abstract = {A recent study by A. Bhosle, M. I. Jackson, A. M. Walsh, E. A. Franzosa, et al. (mSystems 10:e00452-24, 2024, https://doi.org/10.1128/msystems.00452-24) enhances our understanding of dietary fiber's impact on the gut microbiome and metabolome in companion animals, uncovering individual variations in microbial and metabolic responses. By examining short-chain fatty acid (SCFA) profiles in response to fiber, the authors reveal potential therapeutic benefits of tailored dietary interventions, such as enhanced gut and immune health. These findings resonate with human microbiome research, where dietary fiber has shown health benefits through microbial diversity and SCFA production. The study emphasizes the potential for breed-specific responses to fiber, given the variation in microbiome composition and physiology across breeds. Such insights align with emerging concepts of personalized nutrition, offering an opportunity to develop precision dietary strategies that address specific health needs in both veterinary and human contexts. This foundational research positions dietary fiber as a valuable tool in preventive health, providing a roadmap for future studies to refine individualized approaches for gut microbiome modulation.}, }
@article {pmid39923780, year = {2025}, author = {Huang, Z and Liu, Y and Philips, A and Zhang, F and Zuo, T}, title = {Varied prevalence and asymptomatic carriage of Cryptococcus gattii in the gut of Chinese populations.}, journal = {The Lancet. Microbe}, volume = {}, number = {}, pages = {101086}, doi = {10.1016/j.lanmic.2025.101086}, pmid = {39923780}, issn = {2666-5247}, }
@article {pmid39920776, year = {2025}, author = {Han, Y and Teng, TM and Han, J and Kim, HS}, title = {Antibiotic-associated changes in Akkermansia muciniphila alter its effects on host metabolic health.}, journal = {Microbiome}, volume = {13}, number = {1}, pages = {48}, pmid = {39920776}, issn = {2049-2618}, support = {NRF-2018M3A9F3055923 and NRF-2015M3C9A4053393//The national research foundation of the Republic of Korea/ ; }, abstract = {BACKGROUND: Altered gut microbiota has emerged as a major contributing factor to the etiology of chronic conditions in humans. Antibiotic exposure, historically dating back to the mass production of penicillin in the early 1940s, has been proposed as a primary contributor to the cumulative alteration of microbiota over generations. However, the mechanistic link between the antibiotics-altered microbiota and chronic conditions remains unclear.<br><br>RESULTS: In this study, we discovered that variants of the key beneficial gut microbe, Akkermansia muciniphila, were selected upon exposure to penicillin. These variants had mutations in the promoter of a TEM-type &#x3b2;-lactamase gene or pur genes encoding the de novo purine biosynthesis pathway, and they exhibited compromised abilities to mitigate host obesity in a murine model. Notably, variants of A. muciniphila are prevalent in the human microbiome worldwide.<br><br>CONCLUSIONS: These findings highlight a previously unknown mechanism through which antibiotics influence host health by affecting the beneficial capacities of the key gut microbes. Furthermore, the global prevalence of A. muciniphila variants raises the possibility that these variants contribute to global epidemics of chronic conditions, warranting further investigations in human populations. Video Abstract.}, }
@article {pmid39913324, year = {2025}, author = {Huang, H and Mani, J and Vetter, TR and Gan, TJ}, title = {Examining the Impact of the Human Microbiome in the Perioperative Setting.}, journal = {Anesthesia and analgesia}, volume = {}, number = {}, pages = {}, pmid = {39913324}, issn = {1526-7598}, }
@article {pmid39912642, year = {2025}, author = {Masarweh, C and Maldonado-Gomez, M and Paviani, B and Bhattacharya, M and Weng, C-Y and Suarez, C and Ehlers-Cheang, S and Stacy, A and Castillo, J and Krishnakumar, N and Kalanetra, KA and Barile, D and German, JB and Lebrilla, CB and Mills, DA}, title = {Generation of novel prebiotic oligosaccharide pools from fiber drives biological insight in bacterial glycan metabolism.}, journal = {Applied and environmental microbiology}, volume = {}, number = {}, pages = {e0207724}, doi = {10.1128/aem.02077-24}, pmid = {39912642}, issn = {1098-5336}, abstract = {Prebiotic oligosaccharides are dietary supplements that modulate the intestinal gut microbiome by selectively nourishing subsets of the microbial community with a goal to enhance host health. To date, the diversity of polysaccharide compositions in the fiber consumed by humans is not well represented by the limited scope of oligosaccharide compositions present in current commercial prebiotics. Recently, our UC Davis group developed a novel method to generate oligosaccharides from any polysaccharide fiber, termed Fenton's Initiation Toward Defined Oligosaccharide Groups (FITDOG). Using this method, sugar beet pulp (SBP) was transformed into sugar beet oligosaccharides (SBOs) composed of arabinose- and galactose-containing oligosaccharides. Fecal fermentations of SBO and SBP produced similar shifts in donor-specific bacterial communities and acid metabolite profiles with a general enrichment of Bacteroides and Bifidobacterium. However, in vitro tests revealed more Bifidobacterium strains could consume SBO than sugar beet arabinan, and specific strains showed differential consumption of arabinofuranooligosaccharides or galactooligosaccharide (GOS) portions of the SBO pool. Genomic and glycomic comparisons suggest that previously characterized, arabinan-specific, extracellular arabinofuranosidases from Bifidobacterium are not necessary to metabolize the arabino-oligosaccharides within SBO. Synbiotic application of SBO with an SBO-consuming strain Bifidobacterium longum subsp. longum SC596 in serial fecal enrichments resulted in enhanced persistence among 9 of 10 donor feces. This work demonstrates a novel workflow whereby FITDOG creates novel oligosaccharide pools that can provide insight into how compositional differences in fiber drive differential gut fermentation behaviors as well as their downstream health impacts. Moreover, these oligosaccharides may be useful in new prebiotic and synbiotic applications.IMPORTANCEPrebiotics seek to selectively alter the host microbiome composition or function, resulting in a concurrent health benefit to the host. However, commercial prebiotics represent a small fraction of the diversity of food polysaccharide compositions. In this work a novel method, Fenton's Initiation Toward Defined Oligosaccharide Groups (FITDOG) was used to generate an oligosaccharide pool from sugar beet pulp (SBP). Sugar beet oligosaccharides (SBOs) resulted in similar changes to SBP in fecal enrichments; however, SBO could be consumed by more beneficial bifidobacterial strains than the cognate polysaccharide. These results demonstrate how the details of glycan structure have a profound influence on how gut bacteria metabolize food carbohydrates. The implications of this work are relevant to understanding how different dietary sources influence the human microbiome and extend to developing novel oligosaccharide pools for prebiotic applications.}, }
@article {pmid39906620, year = {2025}, author = {Wawrety, W and Kedziora, A}, title = {Role of bacteria in cancers and their therapeutic potential: Review of current knowledge.}, journal = {Iranian journal of basic medical sciences}, volume = {28}, number = {3}, pages = {273-282}, doi = {10.22038/ijbms.2024.77667.16798}, pmid = {39906620}, issn = {2008-3866}, abstract = {Cancers are extremely dynamic diseases that can actively cause refractorines to be gained from applied therapies, which is why they are at the forefront of deaths worldwide. In this literature review, we covered the most recent and important discoveries regarding the influence of human microbiota, including tumor bacteriome, on the development and treatment of cancer. Advances in research on microbial communities have enabled us to discover the role of the human microbiome in the development and course of this disease, helping us understand neoplasms better and design new potential therapies. As we show through our findings, by immunomodulation and the secretion of certain chemical substances, the correct bacteriome of the intestinal tract, respiratory system, or skin can protect humans against cancer development and help during the treatment process. Bacteria also reside inside tumors, forming part of the tumor microenvironment (TME), where they interact with immunological and cancer cells in many complex ways. Some bacteria, such as Pseudomonas aeruginosa or Akkermansia muciniphila, can stimulate anticancer cell-mediated immune responses or even directly lead to cancer cell death. We also present the clinical possibilities of using some live, usually modified bacteria to develop bacteriotherapies. Modifying the gut microbiome to stimulate standard treatment is also important. Research on the microbiome and cancer remains a challenging topic in microbiology, having a great potential for advancements in cancer therapy in the future, and is continuously becoming a more and more popular field of research, as shown by our statistical analysis of PubMed data.}, }
@article {pmid39895074, year = {2025}, author = {Lee, KA and Ul-Haq, A and Seo, H and Jo, S and Kim, S and Song, HY and Kim, HS}, title = {Characteristics of skin microbiome associated with disease severity in systemic sclerosis.}, journal = {Journal of microbiology (Seoul, Korea)}, volume = {63}, number = {1}, pages = {e.2409018}, doi = {10.71150/jm.2409018}, pmid = {39895074}, issn = {1976-3794}, support = {//Korea Health Industry Development Institute/ ; HI21C1888//Ministry of Health and Welfare/ ; //National Research Foundation of Korea/ ; RS-2023-00219563//Ministry of Science and ICT/ ; //Soonchunhyang University Research Fund/ ; }, mesh = {Humans ; *Scleroderma, Systemic/microbiology ; *Skin/microbiology/pathology ; *Microbiota ; Female ; Middle Aged ; Male ; *RNA, Ribosomal, 16S/genetics ; Adult ; *Bacteria/classification/genetics/isolation &amp; purification ; Severity of Illness Index ; Aged ; Biomarkers ; Metagenomics ; }, abstract = {Systemic sclerosis (SSc) is a chronic autoimmune disorder characterised by skin fibrosis and internal organ involvement. Disruptions in the microbial communities on the skin may contribute to the onset of autoimmune diseases that affect the skin. However, current research on the skin microbiome in SSc is lacking. This study aimed to investigate skin microbiome associated with disease severity in SSc. Skin swabs were collected from the upper limbs of 46 healthy controls (HCs) and 36 patients with SSc. Metagenomic analysis based on the 16S rRNA gene was conducted and stratified by cutaneous subtype and modified Rodnan skin score (mRSS) severity. Significant differences in skin bacterial communities were observed between the HCs and patients with SSc, with further significant variations based on subtype and mRSS severity. The identified biomarkers were Bacteroides and Faecalibacterium for patients with diffuse cutaneous SSc with high mRSS (≥ 10) and Mycobacterium and Parabacteroides for those with low mRSS (< 10). Gardnerella, Abies, Lactobacillus, and Roseburia were the biomarkers in patients with limited cutaneous SSc (lcSS) and high mRSS, whereas Coprococcus predominated in patients with lcSS and low mRSS. Cutaneous subtype analysis identified Pediococcus as a biomarker in the HCs, whereas mRSS analysis revealed the presence of Pseudomonas in conjunction with Pediococcus. In conclusion, patients with SSc exhibit distinct skin microbiota compared with healthy controls. Bacterial composition varies by systemic sclerosis cutaneous subtype and skin thickness.}, }
@article {pmid39892949, year = {2025}, author = {McGann, C and Phyu, R and Bittinger, K and Mukhopadhyay, S}, title = {Role of the Microbiome in Neonatal Infection: Pathogenesis and Implications for Management.}, journal = {Clinics in perinatology}, volume = {52}, number = {1}, pages = {147-166}, doi = {10.1016/j.clp.2024.10.010}, pmid = {39892949}, issn = {1557-9840}, mesh = {Humans ; Infant, Newborn ; *Probiotics/therapeutic use ; *Gastrointestinal Microbiome ; *Anti-Bacterial Agents/therapeutic use ; *Fecal Microbiota Transplantation/methods ; Neonatal Sepsis/microbiology/therapy ; Microbiota ; }, abstract = {The human microbiome refers to the collective genome of microorganisms, including bacteria, fungi, and viruses residing on human body surfaces that are in contact with the environment. Together these communities protect against invasive infections. Conversely, when disrupted, the microbiome can be the source of pathogens causing invasive infection. Interventions to manipulate it via probiotics, antibiotics, and fecal transplantation are available. The risk benefit of these interventions remains unclear. In this review, the authors discuss evidence linking the gut microbiome to neonatal sepsis and also discuss the challenges for translating this knowledge into better clinical care.}, }
@article {pmid39891027, year = {2025}, author = {Nissilä, E and Starck, L and Aho, E and Venerandi, E and Jalkanen, P and Leskinen, K and Uvarov, P and Saavalainen, P and Julkunen, I and Kotimaa, J and Haapasalo, K and Meri, S}, title = {The COVID-19 vaccine ChAdOx1 is opsonized by anti-vector antibodies that activate complement and promote viral vector phagocytosis.}, journal = {Scandinavian journal of immunology}, volume = {101}, number = {2}, pages = {e70000}, doi = {10.1111/sji.70000}, pmid = {39891027}, issn = {1365-3083}, support = {4708373//Sigrid Jus&#xe9;liuksen S&#xe4;&#xe4;ti&#xf6;/ ; TYH2023322//Helsingin ja Uudenmaan Sairaanhoitopiiri/ ; 336411//Academy of Finland/ ; 336410//Academy of Finland/ ; }, mesh = {Humans ; *Phagocytosis/immunology ; *SARS-CoV-2/immunology ; *Complement Activation/immunology ; *Immunoglobulin G/immunology/blood ; *ChAdOx1 nCoV-19/immunology ; *Antibodies, Viral/immunology/blood ; *COVID-19/immunology/prevention &amp; control ; Genetic Vectors/immunology ; COVID-19 Vaccines/immunology ; Opsonization/immunology ; Adenoviruses, Human/immunology ; Female ; Male ; Neutrophils/immunology ; Adult ; }, abstract = {The ChAdOx1 nCoV-19 vaccine has been in large-scale use during the COVID-19 pandemic. Limited efficacy compared to mRNA vaccines and certain potential side effects raise the question of whether anti-adenoviral vector antibodies influence immune responses against the vaccine. Complement activation by ChAdOx1 and leukocyte phagocytosis of ChAdOx1 in vitro were studied. Plasma IgG levels against ChAdOx1 and human adenovirus 2 (hAdV2) hexon protein were determined (n = 20) and IgGs from high- and low-titre plasmas were isolated (n = 3). Complement activation was measured as cleavage of C3 by immunoblotting and generation of C3a and sC5b-9 by ELISA. pHrodo-labelled ChAdOx1 was opsonized with complement and IgG, and phagocytosis by isolated blood PMNs in vitro was studied by flow cytometry. The transcriptomic profile of PMN cells exposed to ChAdOx1 was analysed by RNA-seq. ChAdOx1 activated the classical complement pathway in an anti-adenovirus antibody-dependent manner. Generation of the terminal complement complex sC5b-9 in individual sera correlated with anti-hAdV2 hexon and anti-ChAdOx1 IgG levels. Phagocytosis of ChAdOx1 also correlated significantly with anti-hAdV2 hexon IgG, anti-ChAdOx1 IgG and serum sC5b-9 levels. High-titre anti-hAdv2 hexon IgG increased phagocytosis in the presence of normal serum. Anti-vector antibodies induced rapid complement activation and promoted phagocytosis of the ChAdOx1 vaccine by neutrophils. Moreover, transcriptomic analysis revealed upregulation of complement-related genes induced by the ChAdOx1 vaccine in vitro. Anti-adenovirus vector antibodies and complement activation may thus influence the efficacy of the ChAdOx1 vaccine against SARS-CoV-2 and be also involved in vaccine-related side effects.}, }
@article {pmid39886886, year = {2025}, author = {Pitkänen, HH and Helin, T and Khawaja, T and Pietilä, JP and Kajova, M and Välimaa, H and Vahlberg, T and Ihalainen, J and Vierikko, A and Vapalahti, O and Kantele, A and Lassila, R}, title = {Coagulation Profile of Convalescent Plasma Donors and Recipients.}, journal = {Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis}, volume = {31}, number = {}, pages = {10760296251317522}, pmid = {39886886}, issn = {1938-2723}, mesh = {Humans ; Male ; Female ; Middle Aged ; *COVID-19/blood/therapy ; *Immunization, Passive/methods ; Adult ; Double-Blind Method ; *COVID-19 Serotherapy ; *Blood Donors ; Blood Coagulation/drug effects ; SARS-CoV-2 ; Aged ; Plasmapheresis/methods ; }, abstract = {Convalescent plasma (CP) therapy for COVID-19 infection may have favorable safety but varying efficacy, with concerns about its procoagulant impact. We investigated whether administration of CP to hospitalized patients affects their coagulation profile. Fifty-four patients randomized in a double-blinded fashion received either placebo, low-titer CP (LCP) or high-titer CP (HCP). Donor blood samples were obtained at the time of the plasmapheresis, while recipient blood samples were collected before infusion, one day post-infusion and between two and six days after infusion. Routine laboratory follow-up, coagulation biomarkers, antiphospholipid antibodies, and thrombin generation (TG) were assessed. CP donors had normal blood cell counts and coagulation profiles, without differences between LCP and HCP donors at the baseline. All CP recipients were on low-molecular-weight heparin thromboprophylaxis at the time of the infusion. Despite randomization, the HCP group had lower baseline (p = 0.004) and Day 1 platelet counts (p = 0.019) than the LCP group. Von Willebrand antigen (VWF:Ag) levels clearly exceeded normal without differences at baseline. At Day 1, LCP recipients had higher VWF:Ag (mean ± SD 224 ± 15%) than HCP recipients (210 ± 8%) (p = 0.012). In all groups, overall 80% lupus anticoagulant was positive. Baseline TG variables were comparable, but again LCP recipients exhibited higher endogenous thrombin potential (ETP) (1313 ± 535 nM.min) (p = 0.038) and peak TG (184 ± 106 nM) (p = 0.037) than the HCP group (870 ± 425 nM.min and 86 ± 54 nM). Our findings show that LCP increases VWF:Ag levels and enhances TG despite the thromboprophylaxis. These results suggest that HCP induces less hypercoagulability than LCP, which may contribute to the variability in CP efficacy.}, }
@article {pmid39885552, year = {2025}, author = {Koh, H and Kim, J and Jang, H}, title = {MiCML: a causal machine learning cloud platform for the analysis of treatment effects using microbiome profiles.}, journal = {BioData mining}, volume = {18}, number = {1}, pages = {10}, pmid = {39885552}, issn = {1756-0381}, support = {2021R1C1C1013861//National Research Foundation of Korea/ ; }, abstract = {BACKGROUND: The treatment effects are heterogenous across patients due to the differences in their microbiomes, which in turn implies that we can enhance the treatment effect by manipulating the patient's microbiome profile. Then, the coadministration of microbiome-based dietary supplements/therapeutics along with the primary treatment has been the subject of intensive investigation. However, for this, we first need to comprehend which microbes help (or prevent) the treatment to cure the patient's disease.<br><br>RESULTS: In this paper, we introduce a cloud platform, named microbiome causal machine learning (MiCML), for the analysis of treatment effects using microbiome profiles on user-friendly web environments. MiCML is in particular unique with the up-to-date features of (i) batch effect correction to mitigate systematic variation in collective large-scale microbiome data due to the differences in their underlying batches, and (ii) causal machine learning to estimate treatment effects with consistency and then discern microbial taxa that enhance (or lower) the efficacy of the primary treatment. We also stress that MiCML can handle the data from either randomized controlled trials or observational studies.<br><br>CONCLUSION: We describe MiCML as a useful analytic tool for microbiome-based personalized medicine. MiCML is freely available on our web server (http://micml.micloud.kr). MiCML can also be implemented locally on the user's computer through our GitHub repository (https://github.com/hk1785/micml).}, }
@article {pmid39880761, year = {2025}, author = {Nandwana, D and Zhang, Y and Feng, N}, title = {Contribution of the Microbiome to Interstitial Cystitis/Bladder Pain Syndrome: A Mini Review.}, journal = {European urology focus}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.euf.2025.01.008}, pmid = {39880761}, issn = {2405-4569}, abstract = {Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic and debilitating condition characterized by pelvic pain and urinary urgency and frequency with an unclear etiology. Emerging evidence implicates microbiome dysbiosis-disruptions in the microbial communities inhabiting the body-in IC/BPS pathophysiology. This review synthesizes the literature on microbial alterations in IC/BPS, including urinary, vaginal, and gastrointestinal microbiota, and their interactions with host inflammatory and metabolic pathways. PATIENT SUMMARY: We reviewed studies from the past 10 years on microbial communities in the body for patients with interstitial cystitis/bladder pain syndrome (IC/BPS). Studies have revealed significant changes in microbial species for these patients, especially in urine. However, research on whether IC/BPS can be treated with interventions to modify microbial communities in the body is still needed.}, }
@article {pmid39877362, year = {2024}, author = {Slater, AS and Hickey, RM and Davey, GP}, title = {Interactions of human milk oligosaccharides with the immune system.}, journal = {Frontiers in immunology}, volume = {15}, number = {}, pages = {1523829}, pmid = {39877362}, issn = {1664-3224}, mesh = {*Milk, Human/immunology/chemistry/metabolism ; Humans ; *Oligosaccharides/immunology ; *Immune System/metabolism/immunology ; Gastrointestinal Microbiome/immunology ; Animals ; Immunomodulation ; Infant, Newborn ; }, abstract = {Human milk oligosaccharides (HMOs) are abundant, diverse and complex sugars present in human breast milk. HMOs are well-characterized barriers to microbial infection and by modulating the human microbiome they are also thought to be nutritionally beneficial to the infant. The structural variety of over 200 HMOs, including neutral, fucosylated and sialylated forms, allows them to interact with the immune system in various ways. Clinically, HMOs impact allergic diseases, reducing autoimmune and inflammatory responses, and offer beneficial support to the preterm infant immune health. This review examines the HMO composition and associated immunomodulatory effects, including interactions with immune cell receptors and gut-associated immune responses. These immunomodulatory properties highlight the potential for HMO use in early stage immune development and for use as novel immunotherapeutics. HMO research is rapidly evolving and promises innovative treatments for immune-related conditions and improved health outcomes.}, }
@article {pmid39877080, year = {2025}, author = {Fehringer, M and Vogl, T}, title = {Molecular mimicry in the pathogenesis of autoimmune rheumatic diseases.}, journal = {Journal of translational autoimmunity}, volume = {10}, number = {}, pages = {100269}, pmid = {39877080}, issn = {2589-9090}, abstract = {Autoimmune rheumatic diseases (ARDs) are a heterogeneous group of conditions characterized by excessive and misdirected immune responses against the body's own musculoskeletal tissues. Their exact aetiology remains unclear, with genetic, demographic, behavioural and environmental factors implicated in disease onset. One prominent hypothesis for the initial breach of immune tolerance (leading to autoimmunity) is molecular mimicry, which describes structural or sequence similarities between human and microbial proteins (mimotopes). This similarity can lead to cross-reactive antibodies and T-cell receptors, resulting in an immune response against autoantigens. Both commensal microbes in the human microbiome and pathogens can trigger molecular mimicry, thereby potentially contributing to the onset of ARDs. In this review, we focus on the role of molecular mimicry in the onset of rheumatoid arthritis and systemic lupus erythematosus. Moreover, implications of molecular mimicry are also briefly discussed for ankylosing spondylitis, systemic sclerosis and myositis.}, }
@article {pmid39875781, year = {2025}, author = {Tiwari, S and Paramanik, V}, title = {Role of Probiotics in Depression: Connecting Dots of Gut-Brain-Axis Through Hypothalamic-Pituitary Adrenal Axis and Tryptophan/Kynurenic Pathway involving Indoleamine-2,3-dioxygenase.}, journal = {Molecular neurobiology}, volume = {}, number = {}, pages = {}, pmid = {39875781}, issn = {1559-1182}, abstract = {Depression is one of the most disabling mental disorders worldwide and characterized by symptoms including worthlessness, anhedonia, sleep, and appetite disturbances. Recently, studies have suggested that tryptophan (Trp) metabolism plays a key role in depressed mood through serotonin and kynurenine pathway involving enzyme tryptophan 5-monooxygenase (TPH) and indoleamine-2,3-dioxygenase (IDO) respectively. Moreover, during neuroinflammation, IDO is activated by proinflammatory cytokines and affects neurogenesis, cognition, disturbed hypothalamic-pituitary-adrenal (HPA) axis, and gut homeostasis by altering the gut bacteria and its metabolites like Trp derivatives. Furthermore, over the decades, researchers have focused on understanding communication between the human microbiome, especially gut microbiota, and mental health, called gut-brain-axis (GBA), particularly through Trp metabolism. Supplementation of probiotics in depression has gained attention from researchers and clinicians. However, there is limited information about probiotics supplementation on depression involving enzyme IDO and kynurenine pathway metabolites. This review discussed the potential role of probiotics in depression through the tryptophan/kynurenine pathway.}, }
@article {pmid39868147, year = {2025}, author = {Britton, GJ and Mogno, I and Chen-Liaw, A and Plitt, T and Helmus, D and Bongers, G and Brough, I and Colmenero, P and Lam, LH and Bullers, SJ and Penkava, F and Reyes-Mercedes, P and Braun, J and Jacobs, JP and Desch, AN and Gevers, D and Simmons, S and Filer, A and Taylor, PC and Bowness, P and Huttenhower, C and Littman, D and Dubinsky, MC and Raza, K and Tankou, SK and Faith, JJ}, title = {Inflammatory disease microbiomes share a functional pathogenicity predicted by C-reactive protein.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {39868147}, issn = {2692-8205}, support = {F30 DK131862/DK/NIDDK NIH HHS/United States ; R01 DK123749/DK/NIDDK NIH HHS/United States ; R01 DK112978/DK/NIDDK NIH HHS/United States ; R01 DK124133/DK/NIDDK NIH HHS/United States ; IK2 CX001717/CX/CSRD VA/United States ; }, abstract = {We examine disease-specific and cross-disease functions of the human gut microbiome by colonizing germ-free mice, at risk for inflammatory arthritis, colitis, or neuroinflammation, with over 100 human fecal microbiomes from subjects with rheumatoid arthritis, ankylosing spondylitis, multiple sclerosis, ulcerative colitis, Crohn's disease, or colorectal cancer. We find common inflammatory phenotypes driven by microbiomes from individuals with intestinal inflammation or inflammatory arthritis, as well as distinct functions specific to microbiomes from multiple sclerosis patients. Inflammatory disease in mice colonized with human microbiomes correlated with systemic inflammation, measured by C-reactive protein, in the human donors. These cross-disease patterns of human microbiome pathogenicity mirror features of the inflammatory diseases, including therapeutic targets and the presence or absence of systemic inflammation, suggesting shared and disease-specific mechanisms by which the microbiome is shaped and drives pathogenic inflammatory responses.}, }
@article {pmid39866415, year = {2025}, author = {Freibauer, A and Pai, N and RamachandranNair, R}, title = {Characterizing the fecal microbiome in patients on the ketogenic diet for drug resistant epilepsy.}, journal = {Heliyon}, volume = {11}, number = {1}, pages = {e41631}, pmid = {39866415}, issn = {2405-8440}, abstract = {BACKGROUND: The ketogenic diet is a dietary therapy with anti-seizure effects. The efficacy of the diet is variable, with initial animal studies suggesting the intestinal microbiome may have a modulating effect. Initial research on the role of the human microbiome in pediatric epilepsy management has been inconclusive.<br><br>METHODS: In this single-center prospective cohort study, stool samples were collected from 4 patients with drug resistant epilepsy on the ketogenic diet and 9 with drug resistant epilepsy as controls. The samples were analyzed by 16S RNA sequencing.<br><br>RESULTS: A trend towards increased alpha diversity was noted among patients on the ketogenic diet compared to the control group. Patients on the ketogenic diet also trended towards a higher relative abundance of Bacteroidaceae, Ruminococcaceae, and Prevotellaceae species. A subset of the control group had a high relative abundance of Bifidobacterium, which may make them a candidate for a trial of the ketogenic diet as a therapeutic option.<br><br>CONCLUSION: These findings add to the growing field of research of how the ketogenic diet modulates the intestinal microbiome in pediatric epilepsy patients. Future emphasis on multi-centre trials, consistent stool collection practices and the establishment of standardized stool biobanking protocols are needed further to validate these novel findings in a pediatric population.}, }
@article {pmid39866243, year = {2025}, author = {Hao, T and Li, Y and Ren, Q and Zeng, Y and Gao, L and Zhu, W and Liang, J and Lin, Y and Hu, J and Yan, G and Sun, S and Cai, J}, title = {circ-1584 selectively promotes the antitumor activity of the oncolytic virus M1 on pancreatic cancer.}, journal = {Molecular therapy. Oncology}, volume = {33}, number = {1}, pages = {200919}, pmid = {39866243}, issn = {2950-3299}, abstract = {Pancreatic cancer is among the most challenging tumors to treat, and due to its immune tolerance characteristics, existing immunotherapy methods are not effective in alleviating the disease. Oncolytic virus therapy, a potential new strategy for treating pancreatic cancer, also faces the limitation of being ineffective when used alone. Elucidating the key host endogenous circular RNAs (circRNAs) involved in M1 virus-mediated killing of pancreatic ductal adenocarcinoma (PDAC) cells may help overcome this limitation. Here, we report that the oncolytic virus M1, a nonpathogenic alphavirus, exhibits different cell viability-inhibitory effects on different pancreatic cancer cells in the clinical stage. Through high-throughput circRNA sequencing, we found that circRNA expression varies among these cells. Further gain-of-function and loss-of-function experiments have shown that circ-1584 can selectively enhance the anti-pancreatic cancer effects of the M1 virus in vitro and in vivo. Additionally, circ-1584 may negatively regulate miR-578 to modulate the anti-pancreatic cancer effects of the M1 virus. Our findings lay the foundation for using circRNA as an adjuvant to enhance the M1 virus efficacy against pancreatic cancer.}, }
@article {pmid39864562, year = {2025}, author = {Hong, X and Chen, T and Liu, Y and Li, J and Huang, D and Ye, K and Liao, W and Wang, Y and Liu, M and Luan, P}, title = {Design, current states, and challenges of nanomaterials in anti-neuroinflammation: A perspective on Alzheimer's disease.}, journal = {Ageing research reviews}, volume = {105}, number = {}, pages = {102669}, doi = {10.1016/j.arr.2025.102669}, pmid = {39864562}, issn = {1872-9649}, abstract = {Alzheimer's disease (AD), an age-related neurodegenerative disease, brings huge damage to the society, to the whole family and even to the patient himself. However, until now, the etiological factor of AD is still unknown and there is no effective treatment for it. Massive deposition of amyloid-beta peptide(Aβ) and hyperphosphorylation of Tau proteins are acknowledged pathological features of AD. Recent studies have revealed that neuroinflammation plays a pivotal role in the pathology of AD. With the rise of nanomaterials in the biomedical field, researchers are exploring how the unique properties of these materials can be leveraged to develop effective treatments for AD. This article has summarized the influence of neuroinflammation in AD, the design of nanoplatforms, and the current research status and inadequacy of nanomaterials in improving neuroinflammation in AD.}, }
@article {pmid39863780, year = {2025}, author = {Toivonen, E and Sikkinen, J and Salonen, A and Kärkkäinen, O and Koistinen, V and Klåvus, A and Meuronen, T and Heini, T and Maltseva, A and Niku, M and Jääskeläinen, T and Laivuori, H}, title = {Metabolic profiles of meconium in preeclamptic and normotensive pregnancies.}, journal = {Metabolomics : Official journal of the Metabolomic Society}, volume = {21}, number = {1}, pages = {21}, pmid = {39863780}, issn = {1573-3890}, mesh = {Humans ; *Meconium/metabolism/chemistry ; Female ; Pregnancy ; *Pre-Eclampsia/metabolism ; Infant, Newborn ; *Metabolome ; Adult ; Metabolomics/methods ; Male ; Case-Control Studies ; Chromatography, Liquid ; }, abstract = {INTRODUCTION: Preeclampsia (PE) is a common vascular pregnancy disorder affecting maternal and fetal metabolism with severe immediate and long-term consequences in mothers and infants. During pregnancy, metabolites in the maternal circulation pass through the placenta to the fetus. Meconium, a first stool of the neonate, offers a view to maternal and fetoplacental unit metabolism and could add to knowledge on the effects of PE on the fetus and newborn.<br><br>OBJECTIVES: To compare meconium metabolome of infants from PE and normotensive pregnancies.<br><br>METHODS: A cohort of preeclamptic parturients and normotensive controls were recruited in Tampere University Hospital during 2019-2022. Meconium was sampled and its metabolome analyzed using liquid chromatography- mass spectrometry in 48 subjects in each group.<br><br>RESULTS: Differences in abundances of 1263 compounds, of which 19 could be annotated, were detected between the two groups. Several acylcarnitines, androsterone sulfate, three bile acids, amino acid derivatives (phenylacetylglutamine, epsilon-(gamma-glutamyl)lysine and N-(phenylacetyl)glutamic acid), as well as caffeine and paraxanthine were lower in the PE group compared to the control group. Urea and progesterone were higher in the PE group.<br><br>CONCLUSION: PE is associated with alterations in the meconium metabolome of infants. The differing abundances of several metabolites show alterations in the interaction between the fetoplacental unit and mother in PE, but whether they are a cause or an effect of the disorder remains to be further investigated.}, }
@article {pmid39862468, year = {2025}, author = {Amir, S and Kumar, M and Kumar, V and Mohanty, D}, title = {HgutMgene-Miner: In silico genome mining tool for deciphering the drug-metabolizing potential of human gut microbiome.}, journal = {Computers in biology and medicine}, volume = {186}, number = {}, pages = {109679}, doi = {10.1016/j.compbiomed.2025.109679}, pmid = {39862468}, issn = {1879-0534}, abstract = {The biotransformation of drugs by enzymes from the human microbiome can produce active or inactive products, impacting the bioactivity and function of these drugs inside the human host. However, understanding the biotransformation reactions of drug molecules catalyzed by bacterial enzymes in human microbiota is still limited. Hence, to characterize drug utilization capabilities across all the microbial phyla inside the human gut, we have used a knowledge-based approach to develop HgutMgene-Miner software which predicts xenobiotic metabolizing enzymes (XMEs) through genome mining. HgutMgene-Miner derives its predictive power from the MicrobiomeMetDB database, which systematically catalogs all known biotransformation reactions of xenobiotics and primary metabolites mediated by host-associated microbial enzymes. Over 10,000 isolate genomes from 830 different bacterial species found in the Unified Human Gastrointestinal Genome (UHGG) collection have been analyzed by HgutMgene-Miner. This led to the identification of 89,377 xenobiotic metabolizing enzymes (XMEs) across 13 phyla, with the greatest diversity in Bacteroidota, Firmicutes_A, Firmicutes, and Proteobacteria. Bacteroides, Clostridium, and Alitsipes were found to be the richest genera, while Actinomyces were found to encode the fewest XMEs, primarily metabolizing Diclofenac, a nonsteroidal anti-inflammatory drug. Overall, we discovered XMEs in 220 genera, exceeding the number experimentally reported in fewer than 10 genera. Notably, Eggerthella lenta's cgr2 involved in Digoxin inactivation was identified in very distant Holdemania genera, likewise Clostridium leptum's nitroreductase, involved in Nitrazepam metabolism, was found in Fusobacterium. These findings highlight the extensive and diverse distribution of XMEs across microbial taxa.}, }
@article {pmid39858487, year = {2025}, author = {Tahmasebi, H and Arjmand, N and Monemi, M and Babaeizad, A and Alibabaei, F and Alibabaei, N and Bahar, A and Oksenych, V and Eslami, M}, title = {From Cure to Crisis: Understanding the Evolution of Antibiotic-Resistant Bacteria in Human Microbiota.}, journal = {Biomolecules}, volume = {15}, number = {1}, pages = {}, pmid = {39858487}, issn = {2218-273X}, mesh = {Humans ; *Anti-Bacterial Agents/pharmacology/therapeutic use ; *Microbiota/drug effects ; Methicillin-Resistant Staphylococcus aureus/drug effects/genetics ; Drug Resistance, Multiple, Bacterial/genetics ; Bacteria/drug effects/genetics ; Drug Resistance, Bacterial/genetics ; }, abstract = {The growing prevalence of antibiotic-resistant bacteria within the human microbiome has become a pressing global health crisis. While antibiotics have revolutionized medicine by significantly reducing mortality and enabling advanced medical interventions, their misuse and overuse have led to the emergence of resistant bacterial strains. Key resistance mechanisms include genetic mutations, horizontal gene transfer, and biofilm formation, with the human microbiota acting as a reservoir for antibiotic resistance genes (ARGs). Industrialization and environmental factors have exacerbated this issue, contributing to a rise in infections with multidrug-resistant (MDR) bacteria, such as methicillin-resistant Staphylococcus aureus (MRSA) and carbapenem-resistant Enterobacteriaceae. These resistant pathogens compromise the effectiveness of essential treatments like surgical prophylaxis and chemotherapy, increase healthcare costs, and prolong hospital stays. This crisis highlights the need for a global One-Health approach, particularly in regions with weak regulatory frameworks. Innovative strategies, including next-generation sequencing (NGS) technologies, offer promising avenues for mitigating resistance. Addressing this challenge requires coordinated efforts, encompassing research, policymaking, public education, and antibiotic stewardship, to safeguard current antibiotics and foster the development of new therapeutic solutions. An integrated, multidimensional strategy is essential to tackle this escalating problem and ensure the sustainability of effective antimicrobial treatments.}, }
@article {pmid39858007, year = {2025}, author = {Al-Matouq, J and Al-Ghafli, H and Alibrahim, NN and Alsaffar, N and Radwan, Z and Ali, MD}, title = {Unveiling the Interplay Between the Human Microbiome and Gastric Cancer: A Review of the Complex Relationships and Therapeutic Avenues.}, journal = {Cancers}, volume = {17}, number = {2}, pages = {}, pmid = {39858007}, issn = {2072-6694}, abstract = {The human microbiota plays a crucial role in maintaining overall health and well-being. The gut microbiota has been implicated in developing and progressing various diseases, including cancer. This review highlights the related mechanisms and the compositions that influence cancer pathogenesis with a highlight on gastric cancer. We provide a comprehensive overview of the mechanisms by which the microbiome influences cancer development, progression, and response to treatment, with a focus on identifying potential biomarkers for early detection, prevention strategies, and novel therapeutic interventions that leverage microbiome modulation. This comprehensive review can guide future research and clinical practices in understanding and harnessing the microbiome to optimize gastric cancer therapies.}, }
@article {pmid39857728, year = {2025}, author = {Jaimez-Alvarado, S and López-Tenorio, II and Barragán-De Los Santos, J and Bello-Vega, DC and Gómez, FJR and Amedei, A and Berrios-Bárcenas, EA and Aguirre-García, MM}, title = {Gut-Heart Axis: Microbiome Involvement in Restrictive Cardiomyopathies.}, journal = {Biomedicines}, volume = {13}, number = {1}, pages = {}, pmid = {39857728}, issn = {2227-9059}, support = {IN212422//Universidad Nacional Aut&#xf3;noma de M&#xe9;xico/ ; CBF2023-2024-734//Consejo Nacional de Humanidades, Ciencias y Tecnolog&#xed;as/ ; }, abstract = {An intriguing aspect of restrictive cardiomyopathies (RCM) is the microbiome role in the natural history of the disease. These cardiomyopathies are often difficult to diagnose and so result in significant morbidity and mortality. The human microbiome, composed of billions of microorganisms, influences various physiological and pathological processes, including cardiovascular health. Studies have shown that gut dysbiosis, an imbalance in the composition of intestinal bacteria, can contribute to systemic inflammation, a key factor in many cardiovascular conditions. An increase in gut permeability, frequently caused by dysbiosis, allows bacterial endotoxins to enter the bloodstream, activating inflammatory pathways that exacerbate cardiac dysfunction. Recent reports highlight the potential role of microbiome in amyloidogenesis, as certain bacteria produce proteins that accelerate the formation of amyloid fibrils. Concurrently, advancements in amyloidosis treatments have sparked renewed hopes, marking a promising era for managing these kinds of diseases. These findings suggest that the gut-heart axis may be a potential factor in the development and progression of cardiovascular disease like RCM, opening new paths for therapeutic intervention. The aim of this review is to provide a detailed overview of the gut-heart axis, focusing on RCM.}, }
@article {pmid39856391, year = {2025}, author = {Tisza, MJ and Lloyd, RE and Hoffman, K and Smith, DP and Rewers, M and Javornik Cregeen, SJ and Petrosino, JF}, title = {Longitudinal phage-bacteria dynamics in the early life gut microbiome.}, journal = {Nature microbiology}, volume = {10}, number = {2}, pages = {420-430}, pmid = {39856391}, issn = {2058-5276}, support = {U01 DK063821/DK/NIDDK NIH HHS/United States ; U01 DK63865//U.S. Department of Health &amp; Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (National Institute of Diabetes &amp; Digestive &amp; Kidney Diseases)/ ; U01 DK63829//U.S. Department of Health &amp; Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (National Institute of Diabetes &amp; Digestive &amp; Kidney Diseases)/ ; UC4 DK063821/DK/NIDDK NIH HHS/United States ; U01 DK63821//U.S. Department of Health &amp; Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (National Institute of Diabetes &amp; Digestive &amp; Kidney Diseases)/ ; }, mesh = {Humans ; *Gastrointestinal Microbiome ; *Bacteriophages/genetics/physiology/classification ; Infant ; *Bacteria/virology/genetics/classification/isolation &amp; purification ; Child, Preschool ; Longitudinal Studies ; Metagenome ; Diabetes Mellitus, Type 1/microbiology/virology ; Feces/microbiology ; Female ; Male ; Metagenomics ; Infant, Newborn ; }, abstract = {Microbial colonization of the human gut occurs soon after birth, proceeds through well-studied phases and is affected by lifestyle and other factors. Less is known about phage community dynamics during infant gut colonization due to small study sizes, an inability to leverage large databases and a lack of appropriate bioinformatics tools. Here we reanalysed whole microbial community shotgun sequencing data of 12,262 longitudinal samples from 887 children from four countries across four years of life as part of the The Environmental Determinants of Diabetes in the Young (TEDDY) study. We developed an extensive metagenome-assembled genome catalogue using the Marker-MAGu pipeline, which comprised 49,111 phage taxa from existing human microbiome datasets. This was used to identify phage marker genes and their integration into the MetaPhlAn 4 bacterial marker gene database enabled simultaneous assessment of phage and bacterial dynamics. We found that individual children are colonized by hundreds of different phages, which are more transitory than bacteria, accumulating a more diverse phage community over time. Type 1 diabetes correlated with a decreased rate of change in bacterial and viral communities in children aged one and two. The addition of phage data improved the ability of machine learning models to discriminate samples by country. Finally, although phage populations were specific to individuals, we observed trends of phage ecological succession that correlated well with putative host bacteria. This resource improves our understanding of phage-bacteria interactions in the developing early life microbiome.}, }
@article {pmid39855612, year = {2025}, author = {Sutanto, H and Elisa, E and Rachma, B and Fetarayani, D}, title = {Gut Microbiome Modulation in Allergy Treatment: The Role of Fecal Microbiota Transplantation.}, journal = {The American journal of medicine}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.amjmed.2025.01.005}, pmid = {39855612}, issn = {1555-7162}, abstract = {The prevalence of allergic diseases has been rising, paralleling lifestyle changes and environmental exposures that have altered human microbiome composition. This review article examines the intricate relationship between the gut microbiome and allergic diseases, emphasizing the potential of fecal microbiota transplantation as a promising novel treatment approach. It explains how reduced microbial exposure in modern societies contributes to immune dysregulation and the increasing incidence of allergies. The discussion also addresses immune homeostasis and its modulation by the gut microbiome, highlighting the shift from eubiosis to dysbiosis in allergic conditions. Furthermore, this article reviews existing studies and emerging research on the role of fecal microbiota transplantation in restoring microbial balance, providing insights into its mechanisms, efficacy, and safety.}, }
@article {pmid39849586, year = {2025}, author = {Li, L and Geng, Y and Chen, T and Lin, K and Xie, C and Qi, J and Wei, H and Wang, J and Wang, D and Yuan, Z and Wan, Z and Li, T and Luo, Y and Niu, D and Li, J and Yu, H}, title = {Deep learning model targeting cancer surrounding tissues for accurate cancer diagnosis based on histopathological images.}, journal = {Journal of translational medicine}, volume = {23}, number = {1}, pages = {110}, pmid = {39849586}, issn = {1479-5876}, support = {No. 82272965//the National Natural Science Foundation of China/ ; No. 81902877//the National Natural Science Foundation of China/ ; No. 82173067//the National Natural Science Foundation of China/ ; No. 81972245//the National Natural Science Foundation of China/ ; No. 31900505//the National Natural Science Foundation of China/ ; No. 2020J01453//the Natural Science Foundation of Xiamen Municipality/ ; No. 2022A1515012656//Science Fund for Distinguished Young Scholars of Guangdong Province/ ; No. 2021A1515010639//Science Fund for Distinguished Young Scholars of Guangdong Province/ ; No. 2021A1515010134//Science Fund for Distinguished Young Scholars of Guangdong Province/ ; No. 202201011004//Instituto Nacional de Ci&#xea;ncia e Tecnologia Centro de Estudos das Adapta&#xe7;&#xf5;es da Biota Aqu&#xe1;tica da Amaz&#xf4;nia/ ; No. R2021217202512965//the Excellent Talent Training Project of the Sixth Affiliated Hospital of Sun Yat-sen University/ ; No. 2022JBGS07//Chongqing Xinqiao Hospital, Second Affiliated Hospital of Army Medical University/ ; No. 23ykbj007//the Fundamental Research Funds for the Central Universities, Sun Yat-sen University/ ; }, mesh = {Humans ; *Deep Learning ; *Stomach Neoplasms/pathology/diagnosis ; Image Processing, Computer-Assisted/methods ; Neoplasms/pathology/diagnosis ; Tumor Microenvironment ; Reproducibility of Results ; }, abstract = {Accurate and fast histological diagnosis of cancers is crucial for successful treatment. The deep learning-based approaches have assisted pathologists in efficient cancer diagnosis. The remodeled microenvironment and field cancerization may enable the cancer-specific features in the image of non-cancer regions surrounding cancer, which may provide additional information not available in the cancer region to improve cancer diagnosis. Here, we proposed a deep learning framework with fine-tuning target proportion towards cancer surrounding tissues in histological images for gastric cancer diagnosis. Through employing six deep learning-based models targeting region-of-interest (ROI) with different proportions of no-cancer and cancer regions, we uncovered the diagnostic value of non-cancer ROI, and the model performance for cancer diagnosis depended on the proportion. Then, we constructed a model based on MobileNetV2 with the optimized weights targeting non-cancer and cancer ROI to diagnose gastric cancer (DeepNCCNet). In the external validation, the optimized DeepNCCNet demonstrated excellent generalization abilities with an accuracy of 93.96%. In conclusion, we discovered a non-cancer ROI weight-dependent model performance, indicating the diagnostic value of non-cancer regions with potential remodeled microenvironment and field cancerization, which provides a promising image resource for cancer diagnosis. The DeepNCCNet could be readily applied to clinical diagnosis for gastric cancer, which is useful for some clinical settings such as the absence or minimum amount of tumor tissues in the insufficient biopsy.}, }
@article {pmid39848248, year = {2025}, author = {Abdill, RJ and Graham, SP and Rubinetti, V and Ahmadian, M and Hicks, P and Chetty, A and McDonald, D and Ferretti, P and Gibbons, E and Rossi, M and Krishnan, A and Albert, FW and Greene, CS and Davis, S and Blekhman, R}, title = {Integration of 168,000 samples reveals global patterns of the human gut microbiome.}, journal = {Cell}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.cell.2024.12.017}, pmid = {39848248}, issn = {1097-4172}, abstract = {The factors shaping human microbiome variation are a major focus of biomedical research. While other fields have used large sequencing compendia to extract insights requiring otherwise impractical sample sizes, the microbiome field has lacked a comparably sized resource for the 16S rRNA gene amplicon sequencing commonly used to quantify microbiome composition. To address this gap, we processed 168,464 publicly available human gut microbiome samples with a uniform pipeline. We use this compendium to evaluate geographic and technical effects on microbiome variation. We find that regions such as Central and Southern Asia differ significantly from the more thoroughly characterized microbiomes of Europe and Northern America and that composition alone can be used to predict a sample's region of origin. We also find strong associations between microbiome variation and technical factors such as primers and DNA extraction. We anticipate this growing work, the Human Microbiome Compendium, will enable advanced applied and methodological research.}, }
@article {pmid39844296, year = {2025}, author = {Liu, B and Xie, Y and Zhang, Y and Tang, G and Lin, J and Yuan, Z and Liu, X and Wang, X and Huang, M and Luo, Y and Yu, H}, title = {Spatial deconvolution from bulk DNA methylation profiles determines intratumoral epigenetic heterogeneity.}, journal = {Cell &amp; bioscience}, volume = {15}, number = {1}, pages = {7}, pmid = {39844296}, issn = {2045-3701}, support = {81902877//National Natural Science Foundation of China/ ; 82272965//National Natural Science Foundation of China/ ; 82372715//National Natural Science Foundation of China/ ; 82173067//National Natural Science Foundation of China/ ; }, abstract = {BACKGROUND: Intratumoral heterogeneity emerges from accumulating genetic and epigenetic changes during tumorigenesis, which may contribute to therapeutic failure and drug resistance. However, the lack of a quick and convenient approach to determine the intratumoral epigenetic heterogeneity (eITH) limit the application of eITH in clinical settings. Here, we aimed to develop a tool that can evaluate the eITH using the DNA methylation profiles from bulk tumors.<br><br>METHODS: Genomic DNA of three laser micro-dissected tumor regions, including digestive tract surface, central bulk, and invasive front, was extracted from formalin-fixed paraffin-embedded sections of colorectal cancer patients. The genome-wide methylation profiles were generated with methylation array. The most variable methylated probes were selected to construct a DNA methylation-based heterogeneity (MeHEG) estimation tool that can deconvolve the proportion of each reference tumor region with the support vector machine model-based method. A PCR-based assay for quantitative analysis of DNA methylation (QASM) was developed to specifically determine the methylation status of each CpG in MeHEG assay at single-base resolution to realize fast evaluation of epigenetic heterogeneity.<br><br>RESULTS: In the discovery set with 79 patients, the differentially methylated CpGs among the three tumor regions were found. The 7 most representative CpGs were identified and subsequently selected to develop the MeHEG algorithm. We validated its performance of deconvolution of tumor regions in an independent cohort. In addition, we showed the significant association of MeHEG-based epigenetic heterogeneity with the genomic heterogeneity in mutation and copy number variation in our in-house and TCGA cohorts. Besides, we found that the patients with higher MeHEG score had worse disease-free and overall survival outcomes. Finally, we found dynamic change of epigenetic heterogeneity based on MeHEG score in cancer cells under the treatment of therapeutic drugs.<br><br>CONCLUSION: By developing a 7-loci panel using a machine learning approach combined with the QASM assay for PCR-based application, we present a valuable method for evaluating intratumoral heterogeneity. The MeHEG algorithm offers novel insights into tumor heterogeneity from an epigenetic perspective, potentially enriching current knowledge of tumor complexity and providing a new tool for clinical and research applications in cancer biology.}, }
@article {pmid39843757, year = {2025}, author = {Pitashny, M and Kesten, I and Shlon, D and Hur, DB and Bar-Yoseph, H}, title = {The Future of Microbiome Therapeutics.}, journal = {Drugs}, volume = {}, number = {}, pages = {}, pmid = {39843757}, issn = {1179-1950}, abstract = {The human microbiome exerts profound influence over various biological processes within the body. Unlike many host determinants, it represents a readily accessible target for manipulation to promote health benefits. However, existing commercial microbiome-directed products often exhibit low efficacy. Advancements in technology are paving the way for the development of novel microbiome therapeutics, across a wide range of indications. In this narrative review, we provide an overview of state-of-the-art technologies in late-stage development, examining their advantages and limitations. By covering a spectrum, from fecal-derived products to live biotherapeutics, phage therapy, and synthetic biology, we illuminate the path toward the future of microbiome therapeutics.}, }
@article {pmid39840991, year = {2025}, author = {Dufresne, K and Al, KF and Craig, HC and Coleman, CEM and Kasper, KJ and Burton, JP and McCormick, JK}, title = {TSST-1 promotes colonization of Staphylococcus aureus within the vaginal tract by activation of CD8[+] T cells.}, journal = {Infection and immunity}, volume = {}, number = {}, pages = {e0043924}, doi = {10.1128/iai.00439-24}, pmid = {39840991}, issn = {1098-5522}, abstract = {Toxic shock syndrome toxin-1 (TSST-1) is a superantigen produced by Staphylococcus aureus and is the determinant of menstrual toxic shock syndrome (mTSS); however, the impact of TSST-1 on the vaginal environment beyond mTSS is not understood. Herein, we assessed how TSST-1 affects vaginal colonization by S. aureus, host inflammatory responses, and changes in microbial communities within the murine vagina. We demonstrated that TSST-1 induced a CD8[+] T-cell-dependent inflammatory response in 24 h that correlated with S. aureus persistence within the vaginal tract. This increase was due to superantigen-dependent T-cell activation that triggered a change in microbial composition within the vaginal tract. Altogether, this study demonstrates that within the vaginal tract, TSST-1 modulates the vaginal microbiota to favor the survival of S. aureus in the absence of mTSS.IMPORTANCEToxic shock syndrome toxin-1 (TSST-1) is a superantigen toxin produced from Staphylococcus aureus that causes the menstrual form of toxic shock syndrome. This research demonstrates that TSST-1 also has a wider function within the vaginal tract than previously expected. We show that TSST-1, by activating CD8[+] T cells, induces an inflammatory environment that modifies the vaginal microbiota to favor colonization by S. aureus. These are important findings as S. aureus can colonize the human vaginal tract efficiently and subsequently trigger dysbiosis within the microbial communities leading to several adverse outcomes such as decreased fertility, increased risks for sexually transmitted diseases, and issues related to pregnancy and birth.}, }
@article {pmid39839711, year = {2025}, author = {Griffin, EF and Owens, MG}, title = {Dopaminergic neurodegeneration in C. elegans cultivated with Porphorymonas gingivalis.}, journal = {microPublication biology}, volume = {2025}, number = {}, pages = {}, pmid = {39839711}, issn = {2578-9430}, abstract = {Disruption of the human microbiome has emerged as a major contributing factor in the etiology of neurodegenerative disease. Previous work suggests a positive correlation between periodontal inflammation and Parkinson's disease. Here, we show that feeding C. elegans animals Porphorymonas gingivalis causes neurodegeneration that is not additive with neurodegeneration induced by the Parkinson's-associated protein, α-synuclein. In contrast, α-synuclein-expressing animals fed P. gingivalis show additional disruption in basal slowing, suggesting that P. gingivalis induces neurodegeneration while altering neuronal function of extant neurons. Though the mechanism is unclear, these results suggest a relationship between P. gingivalis and neurodegeneration that warrants further investigation.}, }
@article {pmid39839678, year = {2025}, author = {Modha, S and Hughes, J and Orton, RJ and Lytras, S}, title = {Expanding the genomic diversity of human anelloviruses.}, journal = {Virus evolution}, volume = {11}, number = {1}, pages = {veaf002}, pmid = {39839678}, issn = {2057-1577}, abstract = {Anelloviruses are a group of small, circular, single-stranded DNA viruses that are found ubiquitously across mammalian hosts. Here, we explored a large number of publicly available human microbiome datasets and retrieved a total of 829 anellovirus genomes, substantially expanding the known diversity of these viruses. The majority of new genomes fall within the three major human anellovirus genera: Alphatorquevirus, Betatorquevirus, and Gammatorquevirus, while we also present new genomes of the under-sampled Hetorquevirus, Memtorquevirus, and Samektorquevirus genera. We performed recombination analysis and show evidence of extensive recombination across all human anelloviruses. Interestingly, more than 95% of the detected events are between members of the same genus and only 15 inter-genus recombination events were detected. The breakpoints of recombination cluster in hotspots at the ends and outside of the ORF1 gene, while a recombination coldspot was detected within the gene. Our analysis suggests that anellovirus evolution is governed by homologous recombination; however, events between distant viruses or ones producing chimaeric ORF1s likely lead to nonviable recombinants. The large number of genomes further allowed us to examine how essential genomic features vary across anelloviruses. These include functional domains in the ORF1 protein and the nucleotide motif of the replication loop region, required for the viruses' rolling-circle replication. A subset of the genomes assembled in both this and previous studies are completely lacking these essential elements, opening up the possibility that anellovirus intracellular populations contain nonstandard viral genomes. However, low-read depth of the metagenomically assembled contigs may partly explain the lack of some features. Overall, our study highlights key features of anellovirus genomics and evolution, a largely understudied group of viruses whose potential in virus-based therapeutics is recently being explored.}, }
@article {pmid39836666, year = {2025}, author = {Gill, B and Wessels, JM and Hayes, CL and Ratcliffe, J and Wokuri, J and Ball, E and Reid, G and Kaul, R and Rana, J and Alkhaifi, M and Tharao, W and Smaill, F and Kaushic, C}, title = {Feasibility, safety and tolerability of estrogen and/or probiotics for improving vaginal health in Canadian African, Caribbean, and Black women: A pilot phase 1 clinical trial.}, journal = {PloS one}, volume = {20}, number = {1}, pages = {e0315576}, pmid = {39836666}, issn = {1932-6203}, mesh = {Humans ; Female ; *Probiotics/administration &amp; dosage/adverse effects ; Adult ; *Vagina/microbiology ; *Estrogens/administration &amp; dosage ; Middle Aged ; Young Adult ; Adolescent ; Pilot Projects ; Canada ; Black People ; Vaginosis, Bacterial/drug therapy ; Feasibility Studies ; Administration, Intravaginal ; Caribbean Region ; Prospective Studies ; HIV Infections ; }, abstract = {BACKGROUND: A dysbiotic vaginal microbiome (VMB) is associated with clinical conditions such as bacterial vaginosis (BV) and an increased risk of human immunodeficiency virus (HIV-1) infection. Considering the high prevalence of BV among African, Caribbean and Black (ACB) women, we conducted a prospective, randomized, open-label phase 1 clinical trial to determine the feasibility, safety and tolerability of administering low-dose estrogen, probiotics or both in combination to improve vaginal health and decrease HIV-1 susceptibility.<br><br>METHODS: ACB women aged 18-49 from the Greater Toronto Area (GTA) were randomized to one of four study arms: intravaginal estradiol (Estring&#xa9;; 7.5mg/day); a vaginal probiotic (RepHresh&#x2122; Pro-B&#x2122;) administered twice daily; a combination of Estring&#xa9; and vaginal RepHresh&#x2122; Pro-B&#x2122; (twice daily); or the Estring&#xa9; and oral RepHresh&#x2122; Pro-B&#x2122; (twice daily), for a duration of 30 days. Feasibility was evaluated through enrolment, retention, and adherence rates, while safety and tolerability were determined by a pre- and post-treatment blood panel and reported adverse events (AEs).<br><br>RESULTS: Overall, 63 ACB women were screened, 50 were enrolled and received the intervention while 41 completed the study, resulting in 80% enrollment and 82% retention rates. Overall adherence to the study protocol was high at 93%, with an adherence of 92% for RepHresh&#x2122; Pro-B&#x2122; and 97% for Estring&#xa9;. A total of 88 AEs were reported by 29 participants which were mild (66/88; 75%) and largely resolved (82/88;93%) by the end of the study, with no serious AEs (SAEs) noted. In addition, a panel of safety blood markers measured pre- and post-intervention confirmed no clinically significant changes in blood chemistry or blood cell count.<br><br>CONCLUSION: Overall, the administration of intravaginal estrogen and/or probiotics in pre-menopausal ACB women is feasible, safe, and well tolerated.<br><br>TRIAL REGISTRATION: The trial was registered with Clinicaltrials.gov (NCT03837015) and CIHR HIV Clinical Trials (CTN308).}, }
@article {pmid39829898, year = {2025}, author = {Ni, M and Fan, Y and Liu, Y and Li, Y and Qiao, W and Davey, LE and Zhang, XS and Ksiezarek, M and Mead, E and Touracheau, A and Jiang, W and Blaser, MJ and Valdivia, RH and Fang, G}, title = {Epigenetic phase variation in the gut microbiome enhances bacterial adaptation.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {39829898}, issn = {2692-8205}, support = {R35 GM139655/GM/NIGMS NIH HHS/United States ; }, abstract = {The human gut microbiome within the gastrointestinal tract continuously adapts to variations in diet, medications, and host physiology. A central strategy for genetic adaptation is epigenetic phase variation (ePV) mediated by bacterial DNA methylation, which can regulate gene expression, enhance clonal heterogeneity, and enable a single bacterial strain to exhibit variable phenotypic states. Genome-wide and site-specific ePV have been well characterized in human pathogens' antigenic variation and virulence factor production. However, the role of ePV in facilitating adaptation within the human microbiome remains poorly understood. Here, we comprehensively cataloged genome-wide and site-specific ePV in human infant and adult gut microbiomes. First, using long-read metagenomic sequencing, we detected genome-wide ePV mediated by complex structural variations of DNA methyltransferases, highlighting the ones associated with antibiotics or fecal microbiota transplantation. Second, we analyzed an extensive collection of public short-read metagenomic sequencing datasets, uncovering a greater prevalence of genome-wide ePV in the human gut microbiome. Third, we quantitatively detected site-specific ePVs using single-molecule methylation analysis to identify dynamic variations associated with antibiotic treatment or probiotic engraftment. Finally, we performed an in-depth assessment of an Akkermansia muciniphila isolate from an infant, highlighting that ePV can regulate gene expression and enhance the bacterial adaptive capacity by employing a bet-hedging strategy to increase tolerance to differing antibiotics. Our findings indicate that epigenetic modifications are a common and broad strategy used by bacteria in the human gut to adapt to their environment.}, }
@article {pmid39824829, year = {2025}, author = {Jeyaram, K and Lahti, L and Tims, S and Heilig, HGHJ and van Gelder, AH and de Vos, WM and Smidt, H and Zoetendal, EG}, title = {Fermented foods affect the seasonal stability of gut bacteria in an Indian rural population.}, journal = {Nature communications}, volume = {16}, number = {1}, pages = {771}, pmid = {39824829}, issn = {2041-1723}, support = {BT/IN/CREST-Awards/44/KJ/2010-11//Department of Biotechnology, Ministry of Science and Technology (DBT)/ ; 295741, 330887//Academy of Finland (Suomen Akatemia)/ ; }, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Seasons ; India ; *Rural Population ; Male ; Female ; Adult ; Bacteria/classification/genetics/isolation &amp; purification ; Fermented Foods/microbiology ; Feces/microbiology ; Middle Aged ; Prevotella/isolation &amp; purification ; Young Adult ; Bifidobacterium/isolation &amp; purification ; }, abstract = {The effect of fermented foods on healthy human gut microbiota structure and function, particularly its seasonal preference and frequent long-term consumption, has been largely uncharacterised. Here, we assess the gut microbiota and metabolite composition of 78 healthy Indian agrarian individuals who differ in the intake of fermented milk and soybean products by seasonal sampling during hot-humid summer, autumn and dry winter. Here we show that, seasonal shifts between the Prevotella- and Bifidobacterium/Ruminococcus-driven community types, or ecological states, and associated fatty acid derivatives, with a bimodal change in Bacteroidota community structure during summer, particularly in fermented milk consumers. Our results associate long-term fermented food consumption with reduced gut microbiota diversity and bacterial load. We identify taxonomic groups that drive the seasonal fluctuation and associated shifts between the two ecological states in gut microbiota. This understanding may pave the way towards developing strategies to sustain a healthy and resilient gut microbiota through dietary interventions.}, }
@article {pmid39824739, year = {2025}, author = {Sfanos, KS}, title = {Clinical translation of the interconnected role of the microbiome and diet in genitourinary malignancies.}, journal = {Urologic oncology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.urolonc.2024.12.269}, pmid = {39824739}, issn = {1873-2496}, abstract = {A complex and often under-appreciated relationship exists between the human microbiome, diet, and the development or progression of cancer. There is likewise an emerging appreciation for the role that the human-associated microbiota play in mediating cancer treatment response. This seminar series covers our current understanding of the interplay between the microbiome and cancer in genitourinary malignancies inclusive of bladder, kidney, and prostate cancers.}, }
@article {pmid39817749, year = {2025}, author = {Amari, Y and Hosonuma, M and Mizukami, T and Isobe, J and Azetsu, Y and Funayama, E and Maruyama, Y and Tsurui, T and Tajima, K and Sasaki, A and Yamazaki, Y and Nakano, R and Sano, Y and Ishida, A and Nakanishi, T and Mochizuki, S and Yoshizawa, Y and Kumagai, S and Yasuhara, S and Ryu, K and Oguchi, T and Kuramasu, A and Yoshimura, K and Sambe, T and Kobayashi, S and Uchida, N}, title = {Association between the ABCC11 gene polymorphism-determined earwax properties and external auditory canal microbiota in healthy adults.}, journal = {Microbiology spectrum}, volume = {13}, number = {2}, pages = {e0169824}, pmid = {39817749}, issn = {2165-0497}, support = {//Showa University/ ; }, mesh = {Humans ; *Ear Canal/microbiology ; *Polymorphism, Single Nucleotide ; Adult ; *Microbiota/genetics ; Female ; *Cerumen/metabolism/microbiology ; Male ; *Bacteria/genetics/classification/metabolism/isolation &amp; purification ; *ATP-Binding Cassette Transporters/genetics/metabolism ; Young Adult ; Healthy Volunteers ; Middle Aged ; }, abstract = {UNLABELLED: The concept of genome-microbiome interactions, in which the microenvironment determined by host genetic polymorphisms regulates the local microbiota, is important in the pathogenesis of human disease. In otolaryngology, the resident bacterial microbiota is reportedly altered in non-infectious ear diseases, such as otitis media pearls and exudative otitis media. We hypothesized that a single-nucleotide polymorphism in the ATP-binding cassette sub-family C member 11 (ABCC11) gene, which determines earwax properties, regulates the ear canal microbiota. We analyzed ABCC11 gene polymorphisms and ear canal microbiota in healthy individuals to understand the relationship between genome-microbiome interactions in the ear canal. The study included 21 subjects who were divided into two groups: 538GA (9) and 538AA (12). Staphylococcus auricularis and Corynebacterium spp. were observed in the 538GA group, whereas Methylocella spp. was observed in the 538AA group. PICRUSt analysis revealed significant enrichment of certain pathways, such as superpathway of N-acetylglucosamine, N-acetylmannosamine and N-acetylneuraminate degradation, chlorosalicylate degradation, mycothiol biosynthesis, and enterobactin biosynthesis in the GA group, whereas allantoin degradation IV (anaerobic), nitrifier denitrification, starch degradation III, L-valine degradation I, and nicotinate degradation I were significantly enriched in the AA group. The ABCC11 gene polymorphism regulates the composition of the ear canal microbiota and its metabolic pathways. This study revealed a genome-microbiome interaction within the resident microbiota of the external auditory canal that may help to elucidate the pathogenesis of ear diseases and develop novel therapies.<br><br>IMPORTANCE: The ABCC11 gene polymorphism, which determines earwax characteristics, regulates the composition of the ear canal microbiota and its metabolic pathways. We determined the presence of genome-microbiome interactions in the resident microbiota of the ear canal. Future studies should focus on ABCC11 gene polymorphisms to elucidate the pathogenesis of ear diseases and develop therapeutic methods.}, }
@article {pmid39817732, year = {2025}, author = {Bao, Z and Zhang, B and Yao, J and Li, MD}, title = {MultiTax-human: an extensive and high-resolution human-related full-length 16S rRNA reference database and taxonomy.}, journal = {Microbiology spectrum}, volume = {13}, number = {2}, pages = {e0131224}, pmid = {39817732}, issn = {2165-0497}, support = {No. 2021JC06//Research Project of Joint Institue of Tobacco and Health/ ; }, mesh = {Humans ; *RNA, Ribosomal, 16S/genetics ; *Microbiota/genetics ; *Bacteria/genetics/classification/isolation &amp; purification ; Phylogeny ; Databases, Genetic ; }, abstract = {Considering that the human microbiota plays a critical role in health and disease, an accurate and high-resolution taxonomic classification is thus essential for meaningful microbiome analysis. In this study, we developed an automatic system, named MultiTax pipeline, for generating de novo taxonomy from full-length 16S rRNA sequences using the Genome Taxonomy Database and other existing reference databases. We first constructed the MultiTax-human database, a high-resolution resource specifically designed for human microbiome research and clinical applications. The database includes 842,649 high-quality full-length 16S rRNA sequences, extracted from multiple public repositories and human-related studies, offering a comprehensive and accurate portrayal of the human microbiome. To validate the MultiTax-human database, we profiled the human microbiome across various body sites, identified core microbial taxa, and tested its performance using an independent data set. Additionally, the database is equipped with a user-friendly web interface for easy querying and data exploration. The MultiTax-human database is poised to serve as a valuable tool for researchers, enhancing the precision of human microbiome studies and advancing our understanding of its impact on human health and diseases.IMPORTANCEUnderstanding the human microbiome, the collection of microorganisms in and on our bodies, is essential for advancing health research. Current methods often lack precision and consistency, hindering our ability to study these microorganisms effectively. Our study presents the MultiTax-human database, a high-resolution reference tool specifically designed for human microbiome research. By integrating data from multiple sources and employing advanced classification techniques, this database offers an accurate and detailed map of the human microbiome. This resource enhances the ability of researchers and clinicians to explore the roles of microorganisms in health and disease, potentially leading to improved diagnostics, treatments, and insights into various medical conditions.}, }
@article {pmid39809670, year = {2025}, author = {Galeota-Sprung, B and Bhatt, AS and de la Fuente-Nunez, C}, title = {Microproteins: emerging roles as antibiotics.}, journal = {Trends in genetics : TIG}, volume = {41}, number = {2}, pages = {104-106}, doi = {10.1016/j.tig.2024.12.004}, pmid = {39809670}, issn = {0168-9525}, mesh = {*Anti-Bacterial Agents/pharmacology/therapeutic use ; Humans ; Microbiota ; Bacterial Proteins/genetics/metabolism ; Micropeptides ; }, abstract = {Recent advances in computational prediction and experimental techniques have detected previously unknown microproteins, particularly in the human microbiome. These small proteins, produced by diverse microbial species, are emerging as promising candidates for new antibiotics.}, }
@article {pmid39809651, year = {2025}, author = {Liu, X and Meng, L and Song, W and Zhi, M and Wang, P and Liu, B and Du, M and Feng, Q}, title = {Efficacy of Toothpaste Containing Polylysine and Funme Peptide on Oral Microbiome and Oral Health.}, journal = {International dental journal}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.identj.2024.11.017}, pmid = {39809651}, issn = {1875-595X}, abstract = {OBJECTIVE: To evaluate the effect of the toothpaste containing ε-poly-L-lysine (ε-PL) and funme peptide (FP) as key components on oral microbial composition and oral health.<br><br>METHODS: An oral microbiome study was initially carried out to analyze the variation in the oral microbiota before and after use of antimicrobial peptide (AMP) toothpaste. Subsequently, a clinical trial was independently performed to assess the efficacy of AMP toothpaste by measuring the dental plaque index (PLI), volatile sulfur compounds (VSCs) levels, modified bleeding index (mBI), and bleeding on probing rate (BOP%).<br><br>RESULTS: The application of AMP toothpaste increased the &#x3b1; diversity and modified &#x3b2; diversity of oral microbiome across 3 oral niches. AMP toothpaste increased the relative abundance of the commensal oral microbes, and attenuated the abundance of pathogenic bacteria in gingivitis patients to normal levels. The clinical trial showed 44.33% and 12.29% reductions of PLI scores in the test and control groups, respectively, and the test group exhibited a more pronounced decrease in VSC levels. The test group recorded significant reductions in mBI and BOP% by 39.09% and 24.59%, respectively, exceeding the control group's reductions of 4.63% and -0.97% (P < .05).<br><br>CONCLUSION: The formulation of toothpaste with &#x3b5;-PL and FP recalibrated the oral microbiome's diversity and abundance, and mitigated common oral health issues such as plaque, halitosis, and gingivitis while maintaining well safety.<br><br>CLINICAL RELEVANCE: Oral care products containing &#x3b5;-PL and FP can be used as a new treatment for improving oral microbiota and oral diseases.}, }
@article {pmid39804694, year = {2025}, author = {Puller, V and Plaza Oñate, F and Prifti, E and de Lahondès, R}, title = {Impact of simulation and reference catalogues on the evaluation of taxonomic profiling pipelines.}, journal = {Microbial genomics}, volume = {11}, number = {1}, pages = {}, pmid = {39804694}, issn = {2057-5858}, mesh = {Humans ; *Gastrointestinal Microbiome/genetics ; Computer Simulation ; Benchmarking ; Bacteria/classification/genetics ; Metagenomics/methods ; Microbiota/genetics ; }, abstract = {Microbiome profiling tools rely on reference catalogues, which significantly affect their performance. Comparing them is, however, challenging, mainly due to differences in their native catalogues. In this study, we present a novel standardized benchmarking framework that makes such comparisons more accurate. We decided not to customize databases but to translate results to a common reference to use the tools with their native environment. Specifically, we conducted two realistic simulations of gut microbiome samples, each based on a specific taxonomic profiler, and used two different taxonomic references to project their results, namely the Genome Taxonomy Database and the Unified Human Gastrointestinal Genome. To demonstrate the importance of using such a framework, we evaluated four established profilers as well as the impact of the simulations and that of the common taxonomic references on the perceived performance of these profilers. Finally, we provide guidelines to enhance future profiler comparisons for human microbiome ecosystems: (i) use or create realistic simulations tailored to your biological context (BC), (ii) identify a common feature space suited to your BC and independent of the catalogues used by the profilers and (iii) apply a comprehensive set of metrics covering accuracy (sensitivity/precision), overall representativity (richness/Shannon) and quantification (UniFrac and/or Aitchison distance).}, }
@article {pmid39802902, year = {2024}, author = {Li, D and Wu, R and Yu, Q and Tuo, Z and Wang, J and Yoo, KH and Wei, W and Yang, Y and Ye, L and Guo, Y and Chaipanichkul, P and Okoli, UA and Poolman, TM and Burton, JP and Cho, WC and Heavey, S and Feng, D}, title = {Microbiota and urinary tumor immunity: Mechanisms, therapeutic implications, and future perspectives.}, journal = {Chinese journal of cancer research = Chung-kuo yen cheng yen chiu}, volume = {36}, number = {6}, pages = {596-615}, pmid = {39802902}, issn = {1000-9604}, }
@article {pmid39800869, year = {2025}, author = {Zhang, H and Chen, A and Li, S and Chen, K and You, X and Bian, Y and Li, C and Liu, S and Huang, J and Zhang, S}, title = {Spatio-Temporal Change of Skin and Oral Microbiota: A Longitudinal Study of Microbial Diversity and Stability.}, journal = {Electrophoresis}, volume = {46}, number = {1-2}, pages = {92-103}, doi = {10.1002/elps.202400160}, pmid = {39800869}, issn = {1522-2683}, support = {82371896//National Natural Science Foundation of China/ ; 82260335//National Natural Science Foundation of China/ ; }, mesh = {Humans ; *Microbiota ; *Skin/microbiology ; Longitudinal Studies ; *Mouth/microbiology ; *COVID-19/microbiology ; SARS-CoV-2/isolation &amp; purification ; Bacteria/classification/isolation &amp; purification ; Saliva/microbiology ; Adult ; Male ; Female ; RNA, Ribosomal, 16S/analysis/genetics ; }, abstract = {The human skin and oral cavity harbor complex microbial communities, which exist in dynamic equilibrium with the host's physiological state and the external environment. This study investigates the microbial atlas of human skin and oral cavities using samples collected over a 10-month period, aiming to assess how both internal and external factors influence the human microbiome. We examined bacterial community diversity and stability across various body sites, including palm and nasal skin, saliva, and oral epithelial cells, during environmental changes and a COVID-19 pandemic. The skin microbiome was confirmed to display spatial and temporal stability compared to the oral microbiome, particularly the oral epithelium, which was susceptible to changes in the host's physiological state and immune response. Moreover, significant differences in the microbial community structure among the 4 sample types were observed, and 87 distinct bacteria biomarkers were identified. The random forest prediction model achieved an overall prediction accuracy of 95.24% across the four types of samples studied. Additionally, nasal skin samples showed significant promise for individual identification through profiling the skin microbiota. These findings highlight the potential of skin and oral microbiota as forensic markers for inferring body sites and identifying individuals. In summary, despite facing limitations such as a small cohort size and the need for broader validation, this research provides an overall perspective and initial insights for refining experimental designs and conducting in-depth research in various microbial research fields.}, }
@article {pmid39798621, year = {2025}, author = {Heckmann, ND and Culler, M and Mont, MA and Lieberman, JR and Parvizi, J}, title = {Emerging Concepts in Periprosthetic Joint Infection Research: The Human Microbiome.}, journal = {The Journal of arthroplasty}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.arth.2025.01.001}, pmid = {39798621}, issn = {1532-8406}, abstract = {Microorganisms, including bacteria, fungi, and viruses, that reside on and within the human body are collectively known as the human microbiome. Dysbiosis, or disruption in the microbiome, has been implicated in several disease processes, including asthma, obesity, autoimmune diseases, and numerous other conditions. While the Human Microbiome Project (HMP) and the generation of descriptive studies it inspired established correlations between characteristic patterns in the composition of the microbiome and specific disease phenotypes, current research has begun to focus on elucidating the causal role of the microbiome in disease pathogenesis. Within the field of orthopaedic surgery, researchers have proposed the concept of a "gut-joint axis" by which the intestinal microbiome influences joint health and the development of diseases such as osteoarthritis and periprosthetic joint infection (PJI). It is theorized that intestinal dysbiosis increases gut permeability, leading to the translocation of bacteria and their metabolic products into the systemic circulation and the stimulation of proinflammatory response cascades throughout the body, including within the joints. While correlative studies have identified patterns of dysbiotic derangement associated with osteoarthritis and PJI, translational research is needed to clarify the precise mechanisms by which these changes influence disease processes. Additionally, an emerging body of literature has challenged the previously held belief that certain body sites are sterile and do not possess a microbiome, with studies identifying distinct microbial genomic signatures and a core microbiome that varies between anatomic sites. A more thorough characterization of the joint microbiome may have profound implications for our understanding of PJI pathogenesis and our ability to stratify patients based on risk. The purpose of this review was to outline our current understanding of the human microbiome, to describe the gut-joint axis and its role in specific pathologies, including PJI, and to highlight the potential of microbiome-based therapeutic interventions in the field of orthopaedics.}, }
@article {pmid39797472, year = {2025}, author = {Chong-Nguyen, C and Yilmaz, B and Coles, B and Sokol, H and MacPherson, A and Siepe, M and Reineke, D and Mosbahi, S and Tomii, D and Nakase, M and Atighetchi, S and Ferro, C and Wingert, C and Gräni, C and Pilgrim, T and Windecker, S and Blasco, H and Dupuy, C and Emond, P and Banz, Y and Losmanovà, T and Döring, Y and Siontis, GCM}, title = {A scoping review evaluating the current state of gut microbiota and its metabolites in valvular heart disease physiopathology.}, journal = {European journal of clinical investigation}, volume = {}, number = {}, pages = {e14381}, doi = {10.1111/eci.14381}, pmid = {39797472}, issn = {1365-2362}, abstract = {BACKGROUND: The human microbiome is crucial in regulating intestinal and systemic functions. While its role in cardiovascular disease is better understood, the link between intestinal microbiota and valvular heart diseases (VHD) remains largely unexplored.<br><br>METHODS: Peer-reviewed studies on human, animal or cell models analysing gut microbiota profiles published up to April 2024 were included. Eligible studies used 16S rRNA or shotgun sequencing, metabolite profiling by mass spectrometry, and examined osteogenesis or fibrosis signalling in valve cells. Methods and findings were qualitatively analysed, with data charted to summarize study design, materials and outcomes.<br><br>RESULTS: Thirteen studies were included in the review: five human, three animal and five in&#xa0;vitro. Of the nine studies on calcific aortic stenosis (CAS), elevated trimethylamine N-oxide (TMAO) levels were linked to an increased risk of cardiovascular events in cohort studies, with CAS patients showing higher levels of Bacteroides plebeius, Enterobacteriaceae, Veillonella dispar and Prevotella copri. In&#xa0;vivo, TMAO promoted aortic valve fibrosis, while tryptophan derivatives stimulated osteogenic differentiation and interleukin-6 secretion in valvular interstitial cells. Two studies on rheumatic mitral valve disease found altered microbiota profiles and lower short-chain fatty acid levels, suggesting potential impacts on immune regulation. Two studies on Barlow's mitral valve disease in animal models revealed elevated TMAO levels in dogs with congestive heart failure, reduced Paraprevotellaceae, increased Actinomycetaceae and dysbiosis involving Turicibacter and E.&#x2009;coli.<br><br>CONCLUSIONS: TMAO has been mainly identified as a prognostic marker in VHD. Gut microbiota dysbiosis has been observed in various forms of VHD and deserve further study.}, }
@article {pmid39796469, year = {2024}, author = {Wu, F and Guo, Y and Wang, Y and Sui, X and Wang, H and Zhang, H and Xin, B and Yang, C and Zhang, C and Jiang, S and Qu, L and Feng, Q and Dai, Z and Shi, C and Li, Y}, title = {Effects of Long-Term Fasting on Gut Microbiota, Serum Metabolome, and Their Association in Male Adults.}, journal = {Nutrients}, volume = {17}, number = {1}, pages = {}, pmid = {39796469}, issn = {2072-6643}, support = {2022SY54B0506, BJH22WS1J002, 18035020103//the Advanced Space Medico-Engineering Research Project of China/ ; SMFA22Q03, SMFA22B04//The State Key Laboratory of Space Medicine, China Astronaut Research and Training Center/ ; HYZHXM01002//the Space Medical Experiment Project of China Manned Space Program/ ; JCYJ20200109110630285//he Shenzhen Science and Technology Innovation Commission 2020 Basic Research Project/ ; 2022YFA1604504//National Key R&amp;D Program of China/ ; }, mesh = {Humans ; Male ; *Gastrointestinal Microbiome/physiology ; *Fasting/blood ; *Metabolome ; Pilot Projects ; Adult ; Animals ; Obesity/microbiology/blood ; Bacteria/classification ; Diet, High-Fat ; }, abstract = {BACKGROUND: Long-term fasting demonstrates greater therapeutic potential and broader application prospects in extreme environments than intermittent fasting.<br><br>METHOD: This pilot study of 10-day complete fasting (CF), with a small sample size of 13 volunteers, aimed to investigate the time-series impacts on gut microbiome, serum metabolome, and their interrelationships with biochemical indices.<br><br>RESULTS: The results show CF significantly affected gut microbiota diversity, composition, and interspecies interactions, characterized by an expansion of the Proteobacteria phylum (about six-fold) and a decrease in Bacteroidetes (about 50%) and Firmicutes (about 34%) populations. Notably, certain bacteria taxa exhibited complex interactions and strong correlations with serum metabolites implicated in energy and amino acid metabolism, with a particular focus on fatty acylcarnitines and tryptophan derivatives. A key focus of our study was the effect of Ruthenibacterium lactatiformans, which was highly increased during CF and exhibited a strong correlation with fat metabolic indicators. This bacterium was found to mitigate high-fat diet-induced obesity, glucose intolerance, dyslipidemia, and intestinal barrier dysfunction in animal experiments. These effects suggest its potential as a probiotic candidate for the amelioration of dyslipidemia and for mediating the benefits of fasting on fat metabolism.<br><br>CONCLUSIONS: Our pilot study suggests that alterations in gut microbiota during CF contribute to the shift of energy metabolic substrate and the establishment of a novel homeostatic state during prolonged fasting.}, }
@article {pmid39796301, year = {2024}, author = {Galazka, S and Vigl, V and Kuffner, M and Dielacher, I and Spettel, K and Kriz, R and Kreuzinger, N and Vierheilig, J and Woegerbauer, M}, title = {Prevalence of Antibiotic Resistance Genes in Differently Processed Smoothies and Fresh Produce from Austria.}, journal = {Foods (Basel, Switzerland)}, volume = {14}, number = {1}, pages = {}, pmid = {39796301}, issn = {2304-8158}, support = {BMASGK-74602/0005-IX/B/15/2019//Austrian Federal Ministry of Social Affairs, Health, Care and Consumer Protection (BMASGK)/ ; }, abstract = {Plant-derived foods are potential vehicles for microbial antibiotic resistance genes (ARGs), which can be transferred to the human microbiome if consumed raw or minimally processed. The aim of this study was to determine the prevalence and the amount of clinically relevant ARGs and mobile genetic elements (MGEs) in differently processed smoothies (freshly prepared, cold-pressed, pasteurized and high-pressure processed) and fresh produce samples (organically and conventionally cultivated) to assess potential health hazards associated with their consumption. The MGE ISPps and the class 1 integron-integrase gene intI1 were detected by probe-based qPCR in concentrations up to 10[4] copies/mL in all smoothies, lettuce, carrots and a single tomato sample. The highest total (2.2 × 10[5] copies/mL) and the most diverse ARG and MGE loads (16/26 targets) were observed in freshly prepared and the lowest prevalences (5/26) and concentrations (4.1 × 10[3] copies/mL) in high-pressure-processed (HPP) smoothies. BlaCTX-M-1-15 (1.2 × 10[5] c/mL) and strB (6.3 × 10[4] c/mL) were the most abundant, and qacEΔ1 (95%), blaTEM1 (85%), ermB and sul1 (75%, each) were the most prevalent ARGs. QnrS, vanA, sat-4, blaKPC, blaNDM-1 and blaOXA-10 were never detected. HPP treatment reduced the microbial loads by ca. 5 logs, also destroying extracellular DNA potentially encoding ARGs that could otherwise be transferred by bacterial transformation. The bacterial microbiome, potential pathogens, bacterial ARG carriers and competent bacteria able to take up ARGs were identified by Illumina 16S rRNA gene sequencing. To reduce the risk of AMR spread from smoothies, our data endorse the application of DNA-disintegrating processing techniques such as HPP.}, }
@article {pmid39794144, year = {2025}, author = {Lan, P and Zhang, ZJ and He, Z}, title = {[Progress in the study of the surgical management of Crohn disease based on the mesenteric concept].}, journal = {Zhonghua wai ke za zhi [Chinese journal of surgery]}, volume = {63}, number = {2}, pages = {107-113}, doi = {10.3760/cma.j.cn112139-20240331-00155}, pmid = {39794144}, issn = {0529-5815}, support = {2022YFA1304000//National Key R&amp;D Program of China/ ; U21A20344//Key Joint Project of National Natural Science Foundation of China/ ; }, abstract = {In recent years, with the deepening of mesentery research, it is found that its blood vessels, nerves, lymphoid tissue, adipose tissue and other structures play an important role in the occurrence and development of Crohn disease, and the degree of lesion is related with the disease process, surgical difficulty, the occurrence of intraoperative complications and postoperative recurrence. The optimal surgical strategy of Crohn disease based on mesenteric involvement has received great attention. Multiple retrospective studies found that extended mesenteric resection and Kono-S anastomosis potentially could reduce the rate of postoperative recurrence. However, the latest prospective randomized controlled studies did not achieve the expected results, and the evidence for the surgical strategy based on mesentery is still weak. This review summarises the findings of basic and clinical investigations of the mesentery in Crohn disease so far and explores its role in surgical treatment optimization, and provides new thinking and insights for the further research and surgical options for Crohn disease.}, }
@article {pmid39793044, year = {2025}, author = {Putumbaka, S and Schut, GJ and Thorgersen, MP and Poole, FL and Shao, N and Rodionov, DA and Adams, MWW}, title = {Tungsten is utilized for lactate consumption and SCFA production by a dominant human gut microbe Eubacterium limosum.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {122}, number = {1}, pages = {e2411809121}, pmid = {39793044}, issn = {1091-6490}, support = {R01 GM136885/GM/NIGMS NIH HHS/United States ; }, mesh = {*Eubacterium/metabolism/genetics ; Humans ; *Gastrointestinal Microbiome/physiology ; *Lactic Acid/metabolism ; *Tungsten/metabolism ; *Fatty Acids, Volatile/metabolism ; Bacterial Proteins/metabolism/genetics ; Gene Expression Regulation, Bacterial ; }, abstract = {Eubacterium limosum is a dominant member of the human gut microbiome and produces short-chain fatty acids (SCFAs). These promote immune system function and inhibit inflammation, making this microbe important for human health. Lactate is a primary source of gut SCFAs but its utilization by E. limosum has not been explored. We show that E. limosum growing on lactate takes up added tungstate rather than molybdate and produces the SCFAs acetate and butyrate, but not propionate. The genes encoding an electron bifurcating, tungsten-containing oxidoreductase (WOR1) and a tungsten-containing formate dehydrogenase (FDH), along with an electron bifurcating lactate dehydrogenase (LCT), lactate permease, and enzymes of the propanediol pathway, are all up-regulated on lactate compared to growth on glucose. Lactate metabolism is controlled by a GntR-family repressor (LctR) and two global regulators, Rex and CcpA, where Rex in part controls W storage and tungstopyranopterin (Tuco) biosynthesis. Tuco-dependent riboswitches, along with CcpA, also control two iron transporters, consistent with the increased iron demand for many iron-containing enzymes, including WOR1 and FDH, involved in SCFA production. From intracellular aldehyde concentrations and the substrate specificity of WOR1, we propose that WOR1 is involved in detoxifying acetaldehyde produced during lactate degradation. Lactate to SCFA conversion by E. limosum is clearly highly tungstocentric and tungsten might be an overlooked micronutrient in the human microbiome and in overall human health.}, }
@article {pmid39792309, year = {2025}, author = {Wang, P and Xia, P and Gao, S and Shi, W and Zhang, X}, title = {Critical Structures of Bisphenol Analogues on Embryonic Toxicity Identified by a Computational Approach.}, journal = {Environmental science &amp; technology}, volume = {59}, number = {3}, pages = {1553-1564}, doi = {10.1021/acs.est.4c10012}, pmid = {39792309}, issn = {1520-5851}, mesh = {*Zebrafish/embryology ; *Phenols/toxicity ; Animals ; Benzhydryl Compounds/toxicity/chemistry ; Embryo, Nonmammalian/drug effects ; Bisphenol A Compounds ; }, abstract = {Safer chemical alternatives to bisphenol (BP) have been a major pursuit of modern green chemistry and toxicology. Using a chemical similarity-based approach, it is difficult to identify minor structural differences that contribute to the significant changes of toxicity. Here, we used omics and computational toxicology to identify chemical features associated with BP analogue-induced embryonic toxicity, offering valuable insights to inform the design of safer chemical alternatives. The zebrafish embryonic acute toxicity, behavioral effects, and concentration-dependent transcriptome analysis of 17 BP analogues were tested, and the chemical structure characteristics and key biological activities-induced embryonic toxicity were explored. BPE, BPF, BPP, BPBP, and BPS induced lower embryonic lethality than BPA. And, 8 BP analogues triggered hyperactive behavior at environmentally and human relevant concentrations. BP analogues with phenol rings linked via hydrophobic segments ("chain:alkaneBranch_neopentyl_C5") disturbed stress response, leading to embryonic lethality, and introducing hydrophobic groups on the meta position of bisphenol structure augmented their embryonic lethality effects. "3DACorr_TotChg_3" of BP analogues is a key physicochemical feature for behavioral disorders, and BP analogues with 3DACorr_TotChg_3 value < 0.11 could induce hyperactive behavior by perturbing neurodevelopment relevant biological pathways. This study provides an integrated strategy, combining data-driven profiling and mechanism-based analysis for safer chemical alternatives.}, }
@article {pmid39791890, year = {2025}, author = {Soborowski, AL and Hackley, RK and Hwang, S and Zhou, G and Dulmage, KA and Schönheit, P and Daniels, C and Bisson-Filho, AW and Marchfelder, A and Maupin-Furlow, JA and Allers, T and Schmid, AK}, title = {Genomic re-sequencing reveals mutational divergence across genetically engineered strains of model archaea.}, journal = {mSystems}, volume = {}, number = {}, pages = {e0108424}, doi = {10.1128/msystems.01084-24}, pmid = {39791890}, issn = {2379-5077}, abstract = {UNLABELLED: Archaeal molecular biology has been a topic of intense research in recent decades as their role in global ecosystems, nutrient cycles, and eukaryotic evolution comes to light. The hypersaline-adapted archaeal species Halobacterium salinarum and Haloferax volcanii serve as important model organisms for understanding archaeal genomics, genetics, and biochemistry, in part because efficient tools enable genetic manipulation. As a result, the number of strains in circulation among the haloarchaeal research community has increased in recent decades. However, the degree of genetic divergence and effects on genetic integrity resulting from the creation and inter-lab transfer of novel lab stock strains remain unclear. To address this, we performed whole-genome re-sequencing on a cross-section of wild-type, parental, and knockout strains in both model species. Integrating these data with existing repositories of re-sequencing data, we identify mutations that have arisen in a collection of 60 strains, sampled from two species across eight different labs. Independent of sequencing, we construct strain lineages, identifying branch points and significant genetic events in strain history. Combining this with our sequencing data, we identify small clusters of mutations that definitively separate lab strains. Additionally, an analysis of gene knockout strains suggests that roughly one in three strains currently in use harbors second-site mutations of potential phenotypic impact. Overall, we find that divergence among lab strains is thus far minimal, though as the archaeal research community continues to grow, careful strain provenance and genomic re-sequencing are required to keep inter-lab divergence to a minimum, prevent the compounding of mutations into fully independent lineages, and maintain the current high degree of reproducible research between lab groups.<br><br>IMPORTANCE: Archaea are a domain of microbial life whose member species play a critical role in the global carbon cycle, climate regulation, the human microbiome, and persistence in extreme habitats. In particular, hypersaline-adapted archaea are important, genetically tractable model organisms for studying archaeal genetics, genomics, and biochemistry. As the archaeal research community grows, keeping track of the genetic integrity of strains of interest is necessary. In particular, routine genetic manipulations and the common practice of sharing strains between labs allow mutations to arise in lab stocks. If these mutations affect cellular processes, they may jeopardize the reproducibility of work between research groups and confound the results of future studies. In this work, we examine DNA sequences from 60 strains across two species of archaea. We identify shared and unique mutations occurring between and within strains. Independently, we trace the lineage of each strain, identifying which genetic manipulations lead to observed off-target mutations. While overall divergence across labs is minimal so far, our work highlights the need for labs to continue proper strain husbandry.}, }
@article {pmid39789171, year = {2025}, author = {Barman, I and Seo, H and Kim, S and Rahim, MA and Yoon, Y and Hossain, MS and Shuvo, MSH and Song, HY}, title = {Isolation of New Strains of Lactic Acid Bacteria from the Vaginal Microbiome of Postmenopausal Women and their Probiotic Characteristics.}, journal = {Current microbiology}, volume = {82}, number = {2}, pages = {76}, pmid = {39789171}, issn = {1432-0991}, support = {20018499//Ministry of Trade, Industry and Energy/ ; RS-2023-00219563//Ministry of Science and ICT, South Korea/ ; Soon Chun Hyang University Research Fund//Soon Chun Hyang University/ ; }, mesh = {Female ; *Probiotics ; Humans ; *Vagina/microbiology ; *Lactobacillales/genetics/isolation &amp; purification/classification/metabolism ; *Postmenopause ; Bacterial Adhesion ; Microbial Sensitivity Tests ; Microbiota ; Anti-Bacterial Agents/pharmacology ; Cytokines/metabolism ; Macrophages/microbiology ; }, abstract = {Lactic acid bacteria (LAB), traditionally consumed as fermented foods, are now being applied to the medical field beyond health-functional food as probiotics. Therefore, it is necessary to continuously discover and evaluate new strains with suitable probiotic characteristics, mainly focusing on safety. In this study, we isolated eight new strains from postmenopausal vaginal fluid using culturomics approaches, an emerging area of interest. Data showed that most strains possessed significant cell surface hydrophobicity (≥ 76%), auto-aggregation capacity (17 to 61%), strong adhesion activity (8 to 34%), and excellent resistance to gastric acid, bile salt, and digestive enzyme, enhancing their survival in the gastrointestinal tract. Moreover, the strains exhibited functional characteristics, including substantial antibacterial activity with a minimal inhibitory concentration (MIC) ranging from 12.5 to 50%. They also harbored bacteriocins genes, produced short-chain fatty acids (acetate and propionate), exhibited significant phagocytic activity, possessed high antioxidative properties, rapidly depleted sodium nitrite, and exhibited proteolysis and β-glucosidase activity. In addition, heat-killed LAB strains significantly reduced the gene expressions of proinflammatory cytokines such as IL-β, IL-6, and iNOS in macrophages. Safety assessment revealed no cytotoxicity in macrophage cell lines. All strains tested negative for biogenic amine or H2O2 production, displayed no gelatinase or hemolytic activity, lacked virulence genes or detrimental enzymes, and displayed antibiotic susceptibility. In summary, these newly isolated strains demonstrate excellent probiotic functionality with a strong focus on safety, making them promising candidates for future drug development in the relevant fields.}, }
@article {pmid39788169, year = {2025}, author = {Xu, B and Luo, Z and Niu, X and Li, Z and Lu, Y and Li, J}, title = {Fungi, immunosenescence and cancer.}, journal = {Seminars in cancer biology}, volume = {109}, number = {}, pages = {67-82}, doi = {10.1016/j.semcancer.2025.01.002}, pmid = {39788169}, issn = {1096-3650}, abstract = {Fungal microbes are a small but immunoreactive component of the human microbiome, which may influence cancer development, progression and therapeutic response. Immunosenescence is a process of immune dysfunction that occurs with aging, including lymphoid organ remodeling, contributing to alterations in the immune system in the elderly, which plays a critical role in many aspects of cancer. There is evidence for the interactions between fungi and immunosenescence in potentially regulating cancer progression and remodeling the tumor microenvironment (TME). In this review, we summarize potential roles of commensal and pathogenic fungi in modulating cancer-associated processes and provide more-detailed discussions on the mechanisms of which fungi affect tumor biology, including local and distant regulation of the TME, modulating antitumor immune responses and interactions with neighboring bacterial commensals. We also delineate the features of immunosenescence and its influence on cancer development and treatment, and highlight the interactions between fungi and immunosenescence in cancer. We discuss the prospects and challenges for harnessing fungi and immunosenescence in cancer diagnosis and/or treatment. Considering the limited understanding and techniques in conducting such research, we also provide our view on how to overcome challenges faced by the exploration of fungi, immunosenescence and their interactions on tumor biology.}, }
@article {pmid39788158, year = {2025}, author = {Theodosiou, AA and Fady, PE and Bennett, N and Read, RC and Bogaert, D and Jones, CE}, title = {Microbiotoxicity: A call to arms for cross-sector protection of the human microbiome.}, journal = {The Journal of infection}, volume = {90}, number = {2}, pages = {106408}, doi = {10.1016/j.jinf.2025.106408}, pmid = {39788158}, issn = {1532-2742}, }
@article {pmid39775305, year = {2025}, author = {Xu, Y and Wang, Z and Li, C and Tian, S and Du, W}, title = {Droplet microfluidics: unveiling the hidden complexity of the human microbiome.}, journal = {Lab on a chip}, volume = {}, number = {}, pages = {}, doi = {10.1039/d4lc00877d}, pmid = {39775305}, issn = {1473-0189}, abstract = {The human body harbors diverse microbial communities essential for maintaining health and influencing disease processes. Droplet microfluidics, a precise and high-throughput platform for manipulating microscale droplets, has become vital in advancing microbiome research. This review introduces the foundational principles of droplet microfluidics, its operational capabilities, and wide-ranging applications. We emphasize its role in enhancing single-cell sequencing technologies, particularly genome and RNA sequencing, transforming our understanding of microbial diversity, gene expression, and community dynamics. We explore its critical function in isolating and cultivating traditionally unculturable microbes and investigating microbial activity and interactions, facilitating deeper insight into community behavior and metabolic functions. Lastly, we highlight its broader applications in microbial analysis and its potential to revolutionize human health research by driving innovations in diagnostics, therapeutic development, and personalized medicine. This review provides a comprehensive overview of droplet microfluidics' impact on microbiome research, underscoring its potential to transform our understanding of microbial dynamics and their relevance to health and disease.}, }
@article {pmid39770796, year = {2024}, author = {Enderlin, D and Bieri, U and Gadient, J and Morsy, Y and Scharl, M and Rüschoff, JH and Hefermehl, LJ and Nikitin, A and Langenauer, J and Engeler, DS and Förster, B and Obrecht, F and Surber, J and Scherer, TP and Eberli, D and Poyet, C}, title = {Towards Reliable Methodology: Microbiome Analysis of Fresh Frozen vs. Formalin-Fixed Paraffin-Embedded Bladder Tissue Samples: A Feasibility Study.}, journal = {Microorganisms}, volume = {12}, number = {12}, pages = {}, pmid = {39770796}, issn = {2076-2607}, support = {KFS-5308-02-2021-R//the Swiss Cancer Research foundation/ ; }, abstract = {Studies have shown that the human microbiome influences the response to systemic immunotherapy. However, only scarce data exist on the impact of the urinary microbiome on the response rates of bladder cancer (BC) to local Bacillus Calmette-Guérin instillation therapy. We launched the prospective SILENT-EMPIRE study in 2022 to address this question. We report the results of the pilot study of SILENT-EMPIRE, which aimed to compare the microbiome between fresh frozen (FF) and formalin-fixed paraffin-embedded (FFPE) samples in the cancerous tissue and adjacent healthy tissue of BC patients. Our results show that alpha diversity is increased in FF samples compared to FFPE (coverage index p = 0.041, core abundance index p = 0.008). No significant differences concerning alpha diversity could be detected between cancerous and non-cancerous tissue in the same BC patients. This study demonstrates that microbiome analysis from both FF and FFPE samples is feasible. Implementing this finding could aid in the translation of research findings into clinical practice.}, }
@article {pmid39770627, year = {2024}, author = {Ricchezze, G and Buratti, E and De Micco, F and Cingolani, M and Scendoni, R}, title = {Medico-Legal Applications of the Human Microbiome and Critical Issues Due to Environmental Transfer: A Review.}, journal = {Microorganisms}, volume = {12}, number = {12}, pages = {}, pmid = {39770627}, issn = {2076-2607}, support = {ECS00000041 - VITALITY - CUP n&#xb0; D83C22000710005//European Union - NextGenerationEU under the Italian Ministry of University and Research (MUR) National Innovation Ecosystem/ ; }, abstract = {Microbiome has recently seen an increase in its forensic applications. It could be employed to identify a suspect when DNA is not available; it can be used to establish postmortem interval (PMI). Furthermore, it could prove to be fundamental in cases of sexual assault. One of the most interesting aspects to study is how microbiomes are transferred. The aim of this review is to analyze the existing literature focusing on the potential transfer of microbiome from humans to environment. Searches on PubMed, Scopus, and Web of Science identified a total of 348 articles. Furthermore, from the bibliographies of the included articles, an additional publication was selected, in accordance with the established inclusion and exclusion criteria. This study has shown the potential of utilizing microbiomes as trace evidence, particularly in connecting individuals to specific environments or objects. However, the variability and dynamics of microbial transfer and persistence need to be carefully addressed.}, }
@article {pmid39763928, year = {2024}, author = {Glowacki, RWP and Engelhart, MJ and Till, JM and Kadam, A and Nemet, I and Sangwan, N and Ahern, PP}, title = {Identification of strain-specific cues that regulate biofilm formation in Bacteroides thetaiotaomicron.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2024.12.20.629428}, pmid = {39763928}, issn = {2692-8205}, abstract = {UNLABELLED: Members of the gut microbiome encounter a barrage of host- and microbe-derived microbiocidal factors that must be overcome to maintain fitness in the intestine. The long-term stability of many gut microbiome strains within the microbiome suggests the existence of strain-specific strategies that have evolved to foster resilience to such insults. Despite this, little is known about the mechanisms that mediate this resistance. Biofilm formation represents one commonly employed defense strategy against stressors like those found in the intestine. Here, we demonstrate strain-level variation in the capacity of the gut symbiont Bacteroides thetaiotaomicron to form biofilms. Despite the potent induction of biofilm formation by purified bile in most strains, we show that the specific bile acid species driving biofilm formation differ among strains, and uncover that a secondary bile-acid, lithocholic acid, and its conjugated forms, potently induce biofilm formation in a strain-specific manner. Additionally, we found that the short-chain fatty acid, acetic acid, could suppress biofilm formation. Thus, our data defines the molecular components of bile that promote biofilm formation in B. thetaiotaomicron and reveals that distinct molecular cues trigger the induction or inhibition of this process. Moreover, we uncover strain-level variation in these responses, thus identifying that both shared and strain-specific determinants govern biofilm formation in this species.<br><br>IMPORTANCE: In order to thrive within the intestine, it is imperative that gut microbes resist the multitude of insults derived from the host immune system and other microbiome members. As such, they have evolved strategies that ensure their survival within the intestine. We investigated one such strategy, biofilm formation, in Bacteroides thetaiotaomicron , a common member of the human microbiome. We uncovered significant variation in natural biofilm formation in the absence of an overt stimulus among different Bacteroides thetaiotaomicron strains, and revealed that different strains adopted a biofilm lifestyle in response to distinct molecular stimuli. Thus our studies provide novel insights into factors mediating gut symbiont resiliency, revealing strain-specific and shared strategies in these responses. Collectively, our findings underscore the prevalence of strain-level differences that should be factored into our understanding of gut microbiome functions.}, }
@article {pmid39757039, year = {2025}, author = {Cruz-Lebrón, A and Faiez, TS and Hess, MM and Sfanos, KS}, title = {Diet and the microbiome as mediators of prostate cancer risk, progression, and therapy response.}, journal = {Urologic oncology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.urolonc.2024.12.001}, pmid = {39757039}, issn = {1873-2496}, abstract = {Complex relationships between the human microbiome and cancer are increasingly recognized for cancer sites that harbor commensal microbial communities such as the gut, genitourinary tract, and skin. For organ sites that likely do not contain commensal microbiota, there is still a substantial capacity for the human-associated microbiota to influence disease etiology across the cancer spectrum. We propose such a relationship for prostate cancer, the most commonly diagnosed cancer in males in the United States. This review explores the current evidence for a role for the urinary and gut microbiota in prostate cancer risk, via both direct interactions (prostate infections) and long-distance interactions such as via the metabolism of procarcinogenic or anticarcinogenic dietary metabolites. We further explore a newly recognized role of the gut microbiota in mediating cancer treatment response or resistance either via production of androgens and/or procarcinogenic metabolites or via direct metabolism of anticancer drugs that are used to treat advanced disease. Overall, we present the current state of knowledge relating to how the human microbiome mediates prostate cancer risk, progression, and therapy response, as well as suggest future research directions for the field.}, }
@article {pmid39754316, year = {2025}, author = {Peng, S and Wu, M and Yan, Q and Xu, G and Xie, Y and Tang, G and Lin, J and Yuan, Z and Liang, X and Yuan, Z and Weng, J and Bai, L and Wang, X and Yu, H and Huang, M and Luo, Y and Liu, X}, title = {Disrupting EDEM3-induced M2-like macrophage trafficking by glucose restriction overcomes resistance to PD-1/PD-L1 blockade.}, journal = {Clinical and translational medicine}, volume = {15}, number = {1}, pages = {e70161}, pmid = {39754316}, issn = {2001-1326}, support = {82372715//National Natural Science Foundation of China/ ; 82173067//National Natural Science Foundation of China/ ; 82272965//National Natural Science Foundation of China/ ; 2024A1515030054//Natural Science Foundation of Guangdong Province/ ; 2022A1515012656//Natural Science Foundation of Guangdong Province/ ; 2018026//Project 5010 of Clinical Medical Research of Sun Yat-sen University-5010 Cultivation Foundation/ ; 2025A04J4447//Science and Technology Program of Guangzhou/ ; 202201011004//Science and Technology Program of Guangzhou/ ; 2022JBGS07//Scientific Research Project of the Sixth Affiliated Hospital of Sun Yat-Sen University/ ; P20150227202010251//Talent Project of the Sixth Affiliated Hospital of Sun Yat-sen University/ ; R2021217202512965//Excellent Talent Training Project of the Sixth Affiliated Hospital of Sun Yat-sen University/ ; 1010CG(2022)-02//Sixth Affiliated Hospital of Sun Yat-sen University Clinical Research-'1010' Program/ ; 1010CG(2022)-03//Sixth Affiliated Hospital of Sun Yat-sen University Clinical Research-'1010' Program/ ; 1010PY(2022)-10)//Sixth Affiliated Hospital of Sun Yat-sen University Clinical Research-'1010' Program/ ; 23ykbj007//Fundamental Research Funds for the Central Universities, Sun Yat-sen University/ ; //Program of Introducing Talents of Discipline to Universities/ ; //National Key Clinical Discipline/ ; }, mesh = {Humans ; Mice ; *Glucose/metabolism ; Animals ; Macrophages/metabolism/immunology/drug effects ; B7-H1 Antigen/metabolism/antagonists &amp; inhibitors ; Immune Checkpoint Inhibitors/pharmacology/therapeutic use ; Colorectal Neoplasms/drug therapy/immunology/metabolism ; Drug Resistance, Neoplasm/drug effects ; Membrane Proteins/metabolism ; Programmed Cell Death 1 Receptor/antagonists &amp; inhibitors/metabolism/immunology ; }, abstract = {BACKGROUND: Immunotherapy is beneficial for some colorectal cancer (CRC) patients, but immunosuppressive networks limit its effectiveness. Cancer-associatedfibroblasts (CAFs) are significant in immune escape and resistance toimmunotherapy, emphasizing the urgent need for new treatment strategies.<br><br>METHODS: Flow cytometric, Western blotting, proteomics analysis, analysis of public database data, genetically modified cell line models, T cell coculture, crystal violetstaining, ELISA, metabonomic and clinical tumour samples were conducted to assess the role of EDEM3 in immune escape and itsmolecular mechanisms. We evaluated theeffects of FMD plus 2-DG on antitumour immunity using multipleximmunofluorescence, flow cytometry, cytokine profiling, TUNEL assays, xenografttumours, and in vivo studies.<br><br>RESULTS: We show thatCAFs upregulate PD-L1 glycosylation and contribute to immune evasion byglycosyltransferase EDEM3. Additionally, EDEM3 plays a role in tumour immunityduring tumour progression. However, the EDEM3-mediated upregulation of PD-L1 expression underpins PD-1/PD-L1 blockade resistance in vivo. This finding contradictsthe previous trend that positive PD-L1 expression indicates a strong responseto PD-1/PD-L1 blockade. Mechanistically, high-EDEM3 expression facilitates M2-like This finding contradictsthe previous trend that positive PD-L1 expression indicates a strong responseto PD-1/PD-L1 blockade.Mechanistically, polarizationand chemotactic migration of macrophages, which are enriched in theperipheral region of tumours compared to thecore region, precluding access of CD8+ T cells to tumourfoci. Furthermore, we EDEM3 predominantly activates the recruited M2-like macrophagesvia a glucose metabolism-dependent mechanism. Manipulationof glucose utilization by a fasting-mimicking diet(FMD) plus 2-DG treatmentsynergistically with PD-1 antibody elicits potent antitumour activity byeffectively decreasing tumour glycosylated PD-L1 expression, augmenting the CD8+effector T cell infiltration and activation while concurrently reducing the infiltration.TheCAFs-EDEM3-M2-like macrophage axis plays a critical role in promotingimmunotherapy resistance. infiltration.TheCAFs-EDEM3-M2-like macrophage axis plays a critical role in promotingimmunotherapy resistance.<br><br>CONCLUSIONS: Our study suggests that blocking EDEM3-induced M2-like macro phage trafficking by FMD plus 2-DG is a promising and effective strategy to overcomeresistance to checkpoint blockade therapy offeringhope for improved treatment outcomes.<br><br>KEY POINTS: Cancer-associated fibroblasts (CAFs) can enhance PD-L1 glycosylation through the glycosyltransferase EDEM3, contributing to immune evasion during tumour progression. EDEM3 predominantly activates the recruit M2-like macrophages via a glucose metabolism-dependent mechanism. Blocking glucose utilization antagonizes recruiting and polarizing M2-like macrophages synergistically with PD-1 antibody to improve anticancer immunity.}, }
@article {pmid39747869, year = {2025}, author = {Wu, W and Zhao, Y and Cheng, X and Xie, X and Zeng, Y and Tao, Q and Yang, Y and Xiao, C and Zhang, Z and Pang, J and Jin, J and He, H and Lin, Y and Li, B and Ma, J and Ye, X and Lin, WJ}, title = {Modulation of glymphatic system by visual circuit activation alleviates memory impairment and apathy in a mouse model of Alzheimer's disease.}, journal = {Nature communications}, volume = {16}, number = {1}, pages = {63}, pmid = {39747869}, issn = {2041-1723}, support = {81972967//National Natural Science Foundation of China (National Science Foundation of China)/ ; 82172526//National Natural Science Foundation of China (National Science Foundation of China)/ ; 82272586//National Natural Science Foundation of China (National Science Foundation of China)/ ; 32271068//National Natural Science Foundation of China (National Science Foundation of China)/ ; 202007030001//Guangzhou Science and Technology Program key projects/ ; 202007030001//Guangzhou Science and Technology Program key projects/ ; 202007030001//Guangzhou Science and Technology Program key projects/ ; }, mesh = {Animals ; *Alzheimer Disease/therapy/metabolism ; *Disease Models, Animal ; Mice ; *Mice, Transgenic ; *Aquaporin 4/metabolism/genetics ; *Memory Disorders/therapy/metabolism ; *Amyloid beta-Peptides/metabolism ; *Glymphatic System/metabolism ; Apathy ; Hippocampus/metabolism ; Male ; Light ; Humans ; }, abstract = {Alzheimer's disease is characterized by progressive amyloid deposition and cognitive decline, yet the pathological mechanisms and treatments remain elusive. Here we report the therapeutic potential of low-intensity 40 hertz blue light exposure in a 5xFAD mouse model of Alzheimer's disease. Our findings reveal that light treatment prevents memory decline in 4-month-old 5xFAD mice and motivation loss in 14-month-old 5xFAD mice, accompanied by restoration of glial water channel aquaporin-4 polarity, improved brain drainage efficiency, and a reduction in hippocampal lipid accumulation. We further demonstrate the beneficial effects of 40 hertz blue light are mediated through the activation of the vLGN/IGL-Re visual circuit. Notably, concomitant use of anti-Aβ antibody with 40 hertz blue light demonstrates improved soluble Aβ clearance and cognitive performance in 5xFAD mice. These findings offer functional evidence on the therapeutic effects of 40 hertz blue light in Aβ-related pathologies and suggest its potential as a supplementary strategy to augment the efficacy of antibody-based therapy.}, }
@article {pmid39747694, year = {2025}, author = {Hsu, TY and Nzabarushimana, E and Wong, D and Luo, C and Beiko, RG and Langille, M and Huttenhower, C and Nguyen, LH and Franzosa, EA}, title = {Profiling lateral gene transfer events in the human microbiome using WAAFLE.}, journal = {Nature microbiology}, volume = {10}, number = {1}, pages = {94-111}, pmid = {39747694}, issn = {2058-5276}, support = {K23DK125838//U.S. Department of Health &amp; Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (National Institute of Diabetes &amp; Digestive &amp; Kidney Diseases)/ ; R24DK110499//U.S. Department of Health &amp; Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (National Institute of Diabetes &amp; Digestive &amp; Kidney Diseases)/ ; Research Scholars Award//American Gastroenterological Association (AGA)/ ; Career Development Award//Crohn's and Colitis Foundation (Crohn's &amp; Colitis Foundation)/ ; T32CA009001//U.S. Department of Health &amp; Human Services | NIH | National Cancer Institute (NCI)/ ; U54DE023798//U.S. Department of Health &amp; Human Services | NIH | National Institute of Dental and Craniofacial Research (NIDCR)/ ; }, mesh = {Humans ; *Gene Transfer, Horizontal ; *Microbiota/genetics ; *Metagenome ; *Phylogeny ; *Algorithms ; Bacteria/genetics/classification/isolation &amp; purification ; Metagenomics/methods ; Genome, Bacterial ; Computational Biology/methods ; }, abstract = {Lateral gene transfer (LGT), also known as horizontal gene transfer, facilitates genomic diversification in microbial populations. While previous work has surveyed LGT in human-associated microbial isolate genomes, the landscape of LGT arising in personal microbiomes is not well understood, as there are no widely adopted methods to characterize LGT from complex communities. Here we developed, benchmarked and validated a computational algorithm (WAAFLE or Workflow to Annotate Assemblies and Find LGT Events) to profile LGT from assembled metagenomes. WAAFLE prioritizes specificity while maintaining high sensitivity for intergenus LGT. Applying WAAFLE to >2,000 human metagenomes from diverse body sites, we identified >100,000 high-confidence previously uncharacterized LGT (~2 per microbial genome-equivalent). These were enriched for mobile elements, as well as restriction-modification functions associated with the destruction of foreign DNA. LGT frequency was influenced by biogeography, phylogenetic similarity of involved pairs (for example, Fusobacterium periodonticum and F. nucleatum) and donor abundance. These forces manifest as networks in which hub taxa donate unequally with phylogenetic neighbours. Our findings suggest that human microbiome LGT may be more ubiquitous than previously described.}, }
@article {pmid39747692, year = {2025}, author = {Olm, MR and Spencer, SP and Takeuchi, T and Silva, EL and Sonnenburg, JL}, title = {Metagenomic immunoglobulin sequencing reveals IgA coating of microbial strains in the healthy human gut.}, journal = {Nature microbiology}, volume = {10}, number = {1}, pages = {112-125}, pmid = {39747692}, issn = {2058-5276}, support = {T32DK007056//U.S. Department of Health &amp; Human Services | National Institutes of Health (NIH)/ ; K08DK134856//U.S. Department of Health &amp; Human Services | National Institutes of Health (NIH)/ ; K08 DK134856/DK/NIDDK NIH HHS/United States ; DP1AT009892//U.S. Department of Health &amp; Human Services | National Institutes of Health (NIH)/ ; T32 DK007056/DK/NIDDK NIH HHS/United States ; F32DK128865//U.S. Department of Health &amp; Human Services | National Institutes of Health (NIH)/ ; }, mesh = {Humans ; *Immunoglobulin A/immunology ; *Gastrointestinal Microbiome/genetics ; *Feces/microbiology ; *Metagenomics/methods ; *Bacteria/genetics/classification/immunology/metabolism ; Host Microbial Interactions/immunology ; Healthy Volunteers ; Intestinal Mucosa/microbiology/immunology/metabolism ; }, abstract = {IgA, the primary human antibody secreted from the gut mucosa, shapes the intestinal microbiota. Methodological limitations have hindered defining which microbial strains are targeted by IgA and the implications of binding. Here we develop a technique, metagenomic immunoglobulin sequencing (MIg-seq), that provides strain-level resolution of microbes coated by IgA and use it to determine IgA coating levels for 3,520 gut microbiome strains in healthy human faeces. We find that both health and disease-associated bacteria are targeted by IgA. Microbial genes are highly predictive of IgA binding levels; in particular, mucus degradation genes are correlated with high binding, and replication rates are significantly reduced for microbes bound by IgA. We demonstrate that IgA binding is more correlated with host immune status than traditional relative abundance measures of microbial community composition. This study introduces a powerful technique for assessing strain-level IgA binding in human stool, paving the way for deeper understanding of IgA-based host-microbe interactions.}, }
@article {pmid39746827, year = {2025}, author = {Goldhawk, DE and Al, KF and Donnelly, SC and Varela-Mattatall, GE and Dassanayake, P and Gelman, N and Prato, FS and Burton, JP}, title = {Assessing microbiota in vivo: debugging with medical imaging.}, journal = {Trends in microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.tim.2024.12.001}, pmid = {39746827}, issn = {1878-4380}, abstract = {The microbiota is integral to human health and has been mostly characterized through various ex vivo 'omic'-based approaches. To better understand the real-time function and impact of the microbiota, in vivo molecular imaging is required. With technologies such as positron emission tomography (PET), magnetic resonance imaging (MRI), and computed tomography (CT), insight into microbiological processes may be coupled to in vivo information. Noninvasive imaging enables longitudinal tracking of microbes and their components in real time; mapping of microbiota biodistribution, persistence and migration; and simultaneous monitoring of host physiological responses. The development of molecular imaging for clinical translation is an interdisciplinary science, with broad implications for deeper understanding of host-microbe interactions and the role(s) of the microbiome in health and disease.}, }
@article {pmid39740900, year = {2025}, author = {Palkovsky, M and Modrackova, N and Neuzil-Bunesova, V and Liberko, M and Soumarova, R}, title = {The Bidirectional Impact of Cancer Radiotherapy and Human Microbiome: Microbiome as Potential Anti-tumor Treatment Efficacy and Toxicity Modulator.}, journal = {In vivo (Athens, Greece)}, volume = {39}, number = {1}, pages = {37-54}, pmid = {39740900}, issn = {1791-7549}, mesh = {Humans ; *Neoplasms/radiotherapy/microbiology ; *Gastrointestinal Microbiome/radiation effects/drug effects ; *Microbiota/radiation effects ; Radiotherapy/adverse effects/methods ; Treatment Outcome ; }, abstract = {Microbiome and radiotherapy represent bidirectionally interacting entities. The human microbiome has emerged as a pivotal modulator of the efficacy and toxicity of radiotherapy; however, a reciprocal effect of radiotherapy on microbiome composition alterations has also been observed. This review explores the relationship between the microbiome and extracranial solid tumors, particularly focusing on the bidirectional impact of radiotherapy on organ-specific microbiome. This article aims to provide a systematic review on the radiotherapy-induced microbial alteration in-field as well as in distant microbiomes. In this review, particular focus is directed to the oral and gut microbiome, its role in the development and progression of cancer, and how it is altered throughout radiotherapy. This review concludes with recommendations for future research, such as exploring microbiome modification to optimize radiotherapy-induced toxicities or enhance its anti-cancer effects.}, }
@article {pmid39738315, year = {2024}, author = {Ecklu-Mensah, G and Miller, R and Maseng, MG and Hawes, V and Hinz, D and Kim, C and Gilbert, JA}, title = {Modulating the human gut microbiome and health markers through kombucha consumption: a controlled clinical study.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {31647}, pmid = {39738315}, issn = {2045-2322}, mesh = {Adult ; Female ; Humans ; Male ; Middle Aged ; *Biomarkers ; Diet, Western/adverse effects ; Feces/microbiology ; *Gastrointestinal Microbiome ; Probiotics/administration &amp; dosage ; Kombucha Tea ; Cholesterol, HDL/blood ; Insulin Resistance ; Inflammation ; }, abstract = {Fermented foods are becoming more popular due to their purported links to metabolic health and the gut microbiome. However, direct clinical evidence for the health claims is lacking. Here, we describe an eight-week clinical trial that explored the effects of a four-week kombucha supplement in healthy individuals consuming a Western diet, randomized into the kombucha (n = 16) or control (n = 8) group. We collected longitudinal stool and blood samples to profile the human microbiome and inflammation markers. We did not observe significant changes in either biochemical parameters or levels of circulating markers of inflammation across the entire cohort. However, paired analysis between baseline and end of intervention time points within kombucha or control groups revealed increases in fasting insulin and in HOMA-IR in the kombucha group whereas reductions in HDL cholesterol were associated with the control group. Shotgun metagenomic analysis revealed the relative abundance of Weizmannia, a kombucha-enriched probiotic and several SCFA producing taxa to be overrepresented in consumers at the end of the intervention. Collectively, in our healthy cohort consuming a Western diet, a short-term kombucha intervention induced modest impacts on human gut microbiome composition and biochemical parameters, which may be attributed to relatively small number of participants and the extensive inter-participant variability.}, }
@article {pmid39735577, year = {2025}, author = {Monshizadeh, M and Hong, Y and Ye, Y}, title = {Multitask knowledge-primed neural network for predicting missing metadata and host phenotype based on human microbiome.}, journal = {Bioinformatics advances}, volume = {5}, number = {1}, pages = {vbae203}, pmid = {39735577}, issn = {2635-0041}, abstract = {MOTIVATION: Microbial signatures in the human microbiome are closely associated with various human diseases, driving the development of machine learning models for microbiome-based disease prediction. Despite progress, challenges remain in enhancing prediction accuracy, generalizability, and interpretability. Confounding factors, such as host's gender, age, and body mass index, significantly influence the human microbiome, complicating microbiome-based predictions.<br><br>RESULTS: To address these challenges, we developed MicroKPNN-MT, a unified model for predicting human phenotype based on microbiome data, as well as additional metadata like age and gender. This model builds on our earlier MicroKPNN framework, which incorporates prior knowledge of microbial species into neural networks to enhance prediction accuracy and interpretability. In MicroKPNN-MT, metadata, when available, serves as additional input features for prediction. Otherwise, the model predicts metadata from microbiome data using additional decoders. We applied MicroKPNN-MT to microbiome data collected in mBodyMap, covering healthy individuals and 25 different diseases, and demonstrated its potential as a predictive tool for multiple diseases, which at the same time provided predictions for the missing metadata. Our results showed that incorporating real or predicted metadata helped improve the accuracy of disease predictions, and more importantly, helped improve the generalizability of the predictive models.<br><br>https://github.com/mgtools/MicroKPNN-MT.}, }
@article {pmid39732609, year = {2025}, author = {Tegegne, HA and Savidge, TC}, title = {Leveraging human microbiomes for disease prediction and treatment.}, journal = {Trends in pharmacological sciences}, volume = {46}, number = {1}, pages = {32-44}, pmid = {39732609}, issn = {1873-3735}, support = {P01 AI152999/AI/NIAID NIH HHS/United States ; T32 AI141349/AI/NIAID NIH HHS/United States ; R01 NR013497/NR/NINR NIH HHS/United States ; P30 DK056338/DK/NIDDK NIH HHS/United States ; R01 DK130517/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Humans ; Computational Biology ; Metagenomics ; *Microbiota ; Precision Medicine/methods ; RNA, Ribosomal, 16S/genetics ; }, abstract = {The human microbiome consists of diverse microorganisms that inhabit various body sites. As these microbes are increasingly recognized as key determinants of health, there is significant interest in leveraging individual microbiome profiles for early disease detection, prevention, and drug efficacy prediction. However, the complexity of microbiome data, coupled with conflicting study outcomes, has hindered its integration into clinical practice. This challenge is partially due to demographic and technological biases that impede the development of reliable disease classifiers. Here, we examine recent advances in 16S rRNA and shotgun-metagenomics sequencing, along with bioinformatics tools designed to enhance microbiome data integration for precision diagnostics and personalized treatments. We also highlight progress in microbiome-based therapies and address the challenges of establishing causality to ensure robust diagnostics and effective treatments for complex diseases.}, }
@article {pmid39731160, year = {2024}, author = {Virtanen, S and Saqib, S and Kanerva, T and Ventin-Holmberg, R and Nieminen, P and Holster, T and Kalliala, I and Salonen, A}, title = {Metagenome-validated combined amplicon sequencing and text mining-based annotations for simultaneous profiling of bacteria and fungi: vaginal microbiota and mycobiota in healthy women.}, journal = {Microbiome}, volume = {12}, number = {1}, pages = {273}, pmid = {39731160}, issn = {2049-2618}, mesh = {Humans ; *Vagina/microbiology ; Female ; *RNA, Ribosomal, 16S/genetics ; *Fungi/genetics/classification/isolation &amp; purification ; *Bacteria/genetics/classification/isolation &amp; purification ; *Microbiota/genetics ; *Metagenome ; *Data Mining ; Metagenomics/methods ; High-Throughput Nucleotide Sequencing/methods ; Sequence Analysis, DNA/methods ; Mycobiome ; Healthy Volunteers ; DNA, Bacterial/genetics ; }, abstract = {BACKGROUND: Amplicon sequencing of kingdom-specific tags such as 16S rRNA gene for bacteria and internal transcribed spacer (ITS) region for fungi are widely used for investigating microbial communities. So far most human studies have focused on bacteria while studies on host-associated fungi in health and disease have only recently started to accumulate. To enable cost-effective parallel analysis of bacterial and fungal communities in human and environmental samples, we developed a method where 16S rRNA gene and ITS1 amplicons were pooled together for a single Illumina MiSeq or HiSeq run and analysed after primer-based segregation. Taxonomic assignments were performed with Blast in combination with an iterative text-extraction-based filtration approach, which uses extensive literature records from public databases to select the most probable hits that were further validated by shotgun metagenomic sequencing.<br><br>RESULTS: Using 50 vaginal samples, we show that the combined run provides comparable results on bacterial composition and diversity to conventional 16S rRNA gene amplicon sequencing. The text-extraction-based taxonomic assignment-guided tool provided ecosystem-specific bacterial annotations that were confirmed by shotgun metagenomic sequencing (VIRGO, MetaPhlAn, Kraken2). Fungi were identified in 39/50 samples with ITS sequencing while in the metagenome data fungi largely remained undetected due to their low abundance and database issues. Co-abundance analysis of bacteria and fungi did not show strong between-kingdom correlations within the vaginal ecosystem of healthy women.<br><br>CONCLUSION: Combined amplicon sequencing for bacteria and fungi provides a simple and cost-effective method for simultaneous analysis of microbiota and mycobiota within the same samples. Conventional metagenomic sequencing does not provide sufficient fungal genome coverage for their reliable detection in vaginal samples. Text extraction-based annotation tool facilitates ecosystem-specific characterization and interpretation of microbial communities by coupling sequence homology to microbe metadata readily available through public databases. Video Abstract.}, }
@article {pmid39724786, year = {2025}, author = {Ma, X and Zhang, J and Jiang, Q and Li, YX and Yang, G}, title = {Human microbiome-derived peptide affects the development of experimental autoimmune encephalomyelitis via molecular mimicry.}, journal = {EBioMedicine}, volume = {111}, number = {}, pages = {105516}, pmid = {39724786}, issn = {2352-3964}, mesh = {*Encephalomyelitis, Autoimmune, Experimental/immunology/etiology/microbiology/metabolism ; Animals ; Humans ; *Molecular Mimicry ; Mice ; *Myelin-Oligodendrocyte Glycoprotein/immunology ; *Gastrointestinal Microbiome ; Multiple Sclerosis/etiology/immunology/microbiology/metabolism ; Peptides/immunology/chemistry ; Disease Models, Animal ; Protein Binding ; CD4-Positive T-Lymphocytes/immunology/metabolism ; Receptors, Antigen, T-Cell/metabolism ; Microbiota ; Peptide Fragments/immunology/metabolism ; Histocompatibility Antigens Class II/metabolism/immunology ; Female ; Computational Biology/methods ; }, abstract = {BACKGROUND: Gut commensal microbiota has been identified as a potential environmental risk factor for multiple sclerosis (MS), and numerous studies have linked the commensal microorganism with the onset of MS. However, little is known about the mechanisms underlying the gut microbiome and host-immune system interaction.<br><br>METHODS: We employed bioinformatics methodologies to identify human microbial-derived peptides by analyzing their similarity to the MHC II-TCR binding patterns of self-antigens. Subsequently, we conducted a range of in&#xa0;vitro and in&#xa0;vivo assays to assess the encephalitogenic potential of these microbial-derived peptides.<br><br>FINDINGS: We analyzed 304,246 human microbiome genomes and 103 metagenomes collected from the MS cohort and identified 731 nonredundant analogs of myelin oligodendrocyte glycoprotein peptide 35-55 (MOG35-55). Of note, half of these analogs could bind to MHC II and interact with TCR through structural modeling of the interaction using fine-tuned AlphaFold. Among the 8 selected peptides, the peptide (P3) shows the ability to activate MOG35-55-specific CD4[+] T cells in&#xa0;vitro. Furthermore, P3 shows encephalitogenic capacity and has the potential to induce EAE in some animals. Notably, mice immunized with a combination of P3 and MOG35-55 develop severe EAE. Additionally, dendritic cells could process and present P3 to MOG35-55-specific CD4[+] T cells and activate these cells.<br><br>INTERPRETATION: Our data suggests the potential involvement of a MOG35-55-mimic peptide derived from the gut microbiota as a molecular trigger of EAE pathogenesis. Our findings offer direct evidence of how microbes can initiate the development of EAE, suggesting a potential explanation for the correlation between certain gut microorganisms and MS prevalence.<br><br>FUNDING: National Natural Science Foundation of China (82371350 to GY).}, }
@article {pmid39723602, year = {2024}, author = {Ma, J and Palmer, DJ and Geddes, D and Lai, CT and Rea, A and Prescott, SL and D'Vaz, N and Stinson, LF}, title = {Maternal Allergic Disease Phenotype and Infant Birth Season Influence the Human Milk Microbiome.}, journal = {Allergy}, volume = {}, number = {}, pages = {}, doi = {10.1111/all.16442}, pmid = {39723602}, issn = {1398-9995}, support = {//Medela/ ; //National Health and Medical Research Council/ ; //University of Western Australia/ ; //Telethon Kids Institute Ascend Fellowship/ ; }, abstract = {Early infancy is a critical period for immune development. In addition to being the primary food source during early infancy, human milk also provides multiple bioactive components that shape the infant gut microbiome and immune system and provides a constant source of exposure to maternal microbiota. Given the potential interplay between allergic diseases and the human microbiome, this study aimed to characterise the milk microbiome of allergic mothers. Full-length 16S rRNA gene sequencing was performed on milk samples collected at 3 and 6 months postpartum from 196 women with allergic disease. Multivariate linear mixed models were constructed to identify the maternal, infant, and environmental determinants of the milk microbiome. Human milk microbiome composition and beta diversity varied over time (PERMANOVA R[2] = 0.011, p = 0.011). The season of infant birth emerged as the strongest determinant of the microbiome community structure (PERMANOVA R[2] = 0.014, p = 0.011) with impacts on five of the most abundant taxa. The milk microbiome also varied according to the type of maternal allergic disease (allergic rhinitis, asthma, atopic dermatitis, and food allergy). Additionally, infant formula exposure reduced the relative abundance of several typical oral taxa in milk. In conclusion, the milk microbiome of allergic mothers was strongly shaped by the season of infant birth, maternal allergic disease phenotype, and infant feeding mode. Maternal allergic disease history and infant season of birth should therefore be considered in future studies of infant and maternal microbiota. Trial Registration: ClinicalTrials.gov identifier: ACTRN12606000281594.}, }
@article {pmid39720963, year = {2024}, author = {Guha, SK and Niyogi, S}, title = {Microbial Dynamics in COVID-19: Unraveling the Impact of Human Microbiome on Disease Susceptibility and Therapeutic Strategies.}, journal = {Current microbiology}, volume = {82}, number = {1}, pages = {59}, pmid = {39720963}, issn = {1432-0991}, mesh = {Humans ; *COVID-19/microbiology/virology ; *SARS-CoV-2 ; *Microbiota ; *Dysbiosis/microbiology ; Disease Susceptibility ; Probiotics/therapeutic use ; Gastrointestinal Microbiome ; }, abstract = {This review explores the bidirectional relationship between the human microbiome and SARS-CoV-2 infection, elucidating its implications for COVID-19 susceptibility, severity, and therapeutic strategies. Metagenomic analyses reveal notable alterations in microbiome composition associated with SARS-CoV-2 infection, impacting disease severity and clinical outcomes. Dysbiosis within the respiratory, gastrointestinal, oral, and skin microbiomes exacerbates COVID-19 pathology through immune dysregulation and inflammatory pathways. Understanding these microbial shifts is pivotal for devising targeted therapeutic interventions. Notably, co-infection of oral pathogens with SARS-CoV-2 worsens lung pathology, while gut microbiome dysbiosis influences viral susceptibility and severity. Potential therapeutic approaches targeting the microbiome include probiotics, antimicrobial agents, and immunomodulatory strategies. This review underscores the importance of elucidating host-microbiota interactions to advance precision medicine and public health initiatives in combating COVID-19 and other infectious diseases.}, }
@article {pmid39717276, year = {2024}, author = {Zhou, Y and Jiang, M and Li, X and Shen, K and Zong, H and Lv, Q and Shen, B}, title = {Bibliometric and visual analysis of human microbiome-breast cancer interactions: current insights and future directions.}, journal = {Frontiers in microbiology}, volume = {15}, number = {}, pages = {1490007}, pmid = {39717276}, issn = {1664-302X}, abstract = {The composition of the gut microbiome differs from that of healthy individuals and is closely linked to the progression and development of breast cancer. Recent studies have increasingly examined the relationship between microbial communities and breast cancer. This study analyzed the research landscape of microbiome and breast cancer, focusing on 736 qualified publications from the Web of Science Core Collection (WoSCC). Publications in this field are on the rise, with the United States leading in contributions, followed by China and Italy. Despite this strong output, the centrality value of China in this field is comparatively low at ninth, highlighting a gap between the quantity of research and its global impact. This pattern is repetitively observed in institutional contributions, with a predominance of Western institutes among the top contributors, underscoring a potential research quality gap in China. Keyword analysis reveals that research hotspots are focused on the effect of microbiome on breast cancer pathogenesis and tumor metabolism, with risk factors and metabolic pathways being the most interesting areas. Publications point to a shift toward anti-tumor therapies and personalized medicine, with clusters such as "anti-tumor" and "potential regulatory agent" gaining prominence. Additionally, intratumor bacteria studies have emerged as a new area of significant interest, reflecting a new direction in research. The University of Helsinki and Adlercreutz H are influential institutions and researchers in this field. Current trends in microbiome and breast cancer research indicate a significant shift toward therapeutic applications and personalized medicine. Strengthening international collaborations and focusing on research quality is crucial for advancing microbiome and breast cancer research.}, }
@article {pmid39717208, year = {2025}, author = {Fallah, A and Sedighian, H and Kachuei, R and Fooladi, AAI}, title = {Human microbiome in post-acute COVID-19 syndrome (PACS).}, journal = {Current research in microbial sciences}, volume = {8}, number = {}, pages = {100324}, pmid = {39717208}, issn = {2666-5174}, abstract = {The global COVID-19 pandemic, which began in 2019, is still ongoing. SARS-CoV-2, also known as the severe acute respiratory syndrome coronavirus 2, is the causative agent. Diarrhea, nausea, and vomiting are common GI symptoms observed in a significant number of COVID-19 patients. Additionally, the respiratory and GI tracts express high level of transmembrane protease serine 2 (TMPRSS2) and angiotensin-converting enzyme-2 (ACE2), making them primary sites for human microbiota and targets for SARS-CoV-2 infection. A growing body of research indicates that individuals with COVID-19 and post-acute COVID-19 syndrome (PACS) exhibit considerable alterations in their microbiome. In various human disorders, including diabetes, obesity, cancer, ulcerative colitis, Crohn's disease, and several viral infections, the microbiota play a significant immunomodulatory role. In this review, we investigate the potential therapeutic implications of the interactions between host microbiota and COVID-19. Microbiota-derived metabolites and components serve as primary mediators of microbiota-host interactions, influencing host immunity. We discuss the various mechanisms through which these metabolites or components produced by the microbiota impact the host's immune response to SARS-CoV-2 infection. Additionally, we address confounding factors in microbiome studies. Finally, we examine and discuss about a range of potential microbiota-based prophylactic measures and treatments for COVID-19 and PACS, as well as their effects on clinical outcomes and disease severity.}, }
@article {pmid39714161, year = {2025}, author = {Neumann, CJ and Mohammadzadeh, R and Woh, PY and Kobal, T and Pausan, M-R and Shinde, T and Haid, V and Mertelj, P and Weiss, E-C and Kolovetsiou-Kreiner, V and Mahnert, A and Kumpitsch, C and Jantscher-Krenn, E and Moissl-Eichinger, C}, title = {First-year dynamics of the anaerobic microbiome and archaeome in infants' oral and gastrointestinal systems.}, journal = {mSystems}, volume = {10}, number = {1}, pages = {e0107124}, pmid = {39714161}, issn = {2379-5077}, support = {10.55776/KLI784 and 10.55776/DOC31//Austrian Science Fund (FWF)/ ; }, mesh = {Humans ; Infant ; *Mouth/microbiology ; *Gastrointestinal Microbiome/physiology ; *Breast Feeding ; Female ; Male ; Archaea/classification ; Gastrointestinal Tract/microbiology ; Anaerobiosis/physiology ; Microbiota/physiology ; Longitudinal Studies ; }, abstract = {UNLABELLED: Recent research provides new insights into the early establishment of the infant gut microbiome, emphasizing the influence of breastfeeding on the development of gastrointestinal microbiomes. In our study, we longitudinally examined the taxonomic and functional dynamics of the oral and gastrointestinal tract (GIT) microbiomes of healthy infants (n = 30) in their first year, focusing on the often-over-looked aspects, the development of archaeal and anaerobic microbiomes. Breastfed (BF) infants exhibit a more defined transitional phase in their oral microbiome compared to non-breastfed (NBF) infants, marked by a decrease in Streptococcus and the emergence of anaerobic genera such as Granulicatella. This phase, characterized by increased alpha-diversity and significant changes in beta-diversity, occurs earlier in NBF infants (months 1-3) than in BF infants (months 4-6), suggesting that breastfeeding supports later, more defined microbiome maturation. We demonstrated the presence of archaea in the infant oral cavity and GIT microbiome from early infancy, with Methanobrevibacter being the predominant genus. Still, transient patterns show that no stable archaeome is formed. The GIT microbiome exhibited gradual development, with BF infants showing increased diversity and complexity between the third and eighth months, marked by anaerobic microbial networks. NBF infants showed complex microbial co-occurrence patterns from the start. These strong differences between BF and NBF infants' GIT microbiomes are less pronounced on functional levels than on taxonomic levels. Overall, the infant microbiome differentiates and stabilizes over the first year, with breastfeeding playing a crucial role in shaping anaerobic microbial networks and overall microbiome maturation.<br><br>IMPORTANCE: The first year of life is a crucial period for establishing a healthy human microbiome. Our study analyses the role of archaea and obligate anaerobes in the development of the human oral and gut microbiome, with a specific focus on the impact of breastfeeding in this process. Our findings demonstrated that the oral and gut microbiomes of breastfed infants undergo distinct phases of increased dynamics within the first year of life. In contrast, the microbiomes of non-breastfed infants are more mature from the first month, leading to a steadier development without distinct transitional phases in the first year. Additionally, we found that archaeal signatures are present in infants under 1 year of age, but they do not form a stable archaeome. In contrast to this, we could track specific bacterial strains transitioning from oral to gut or persisting in the gut over time.}, }
@article {pmid39702789, year = {2025}, author = {Kaur, S and Patel, BCK and Collen, A and Malhotra, R}, title = {The microbiome and the eye: a new era in ophthalmology.}, journal = {Eye (London, England)}, volume = {39}, number = {3}, pages = {436-448}, pmid = {39702789}, issn = {1476-5454}, mesh = {Humans ; *Microbiota/physiology ; *Eye Diseases/microbiology/therapy ; *Ophthalmology ; *Gastrointestinal Microbiome/physiology ; Eye/microbiology ; Fecal Microbiota Transplantation ; }, abstract = {The human microbiome has progressively been recognised for its role in various disease processes. In ophthalmology, complex interactions between the gut and distinct ocular microbiota within each structure and microenvironment of the eye has advanced our knowledge on the multi-directional relationships of these ecosystems. Increasingly, studies have shown that modulation of the microbiome can be achieved through faecal microbiota transplantation and synbiotics producing favourable outcomes for ophthalmic diseases. As ophthalmologists, we are obliged to educate our patients on measures to cultivate a healthy gut microbiome through a range of holistic measures. Further integrative studies combining microbial metagenomics, metatranscriptomics and metabolomics are necessary to fully characterise the human microbiome and enable targeted therapeutic interventions.}, }
@article {pmid39701818, year = {2025}, author = {Evans, SE and Valentine, ME and Gallimore, F and Meka, Y and Koehler, SI and Yu, HD and Valentovic, MA and Long, TE}, title = {Perturbations in the gut microbiome of C57BL/6 mice by the sobriety aid Antabuse® (disulfiram).}, journal = {Journal of applied microbiology}, volume = {136}, number = {1}, pages = {}, pmid = {39701818}, issn = {1365-2672}, support = {P20 GM103434/GM/NIGMS NIH HHS/United States ; R15 AI151970/AI/NIAID NIH HHS/United States ; AI151970//National Institute of Allergy and Infectious Diseases/ ; P20GM103434/NH/NIH HHS/United States ; }, mesh = {Animals ; *Mice, Inbred C57BL ; *Gastrointestinal Microbiome/drug effects ; Mice ; Female ; *Feces/microbiology ; *Disulfiram/pharmacology ; Male ; *RNA, Ribosomal, 16S/genetics ; Microbial Sensitivity Tests ; Ileum/microbiology ; Cecum/microbiology ; Anti-Bacterial Agents/pharmacology ; Peptostreptococcus/drug effects/isolation &amp; purification ; Alcohol Deterrents/pharmacology ; Humans ; Bacteria, Anaerobic/drug effects/isolation &amp; purification ; Porphyromonas/drug effects/isolation &amp; purification ; Clostridium/drug effects/isolation &amp; purification ; Bacteroides/drug effects/isolation &amp; purification ; }, abstract = {AIMS: Disulfiram (Antabuse®) is an oral alcohol sobriety medication that exhibits antimicrobial activity against Gram-positive facultative anaerobes. The aims of this study were to measure the antimicrobial activity against anaerobic bacteria of the gut human microbiome and establish the extent that disulfiram alters the microbial composition of the ileum, cecum, and feces using C57BL/6 mice.<br><br>METHODS AND RESULTS: Antimicrobial susceptibility testing by the microdilution method revealed that disulfiram inhibits the in vitro growth of gut anaerobic species of Bacteroides, Clostridium, Peptostreptococcus, and Porphyromonas. Differential sequencing of 16S rRNA isolated from the ileum, cecum, and feces contents of treated vs. untreated mice showed that disulfiram enriches the Gram-negative enteric population. In female mice, the enrichment was greatest in the ileum, whereas the feces composition in male mice was the most heavily altered.<br><br>CONCLUSIONS: Daily administration of oral disulfiram depletes the enteric Gram-positive anaerobe population as predicted by the minimum inhibitory concentration data for isolates from the human gut microbiota.}, }
@article {pmid39699186, year = {2025}, author = {Lei, Y and Li, M and Zhang, H and Deng, Y and Dong, X and Chen, P and Li, Y and Zhang, S and Li, C and Wang, S and Tao, R}, title = {Comparative analysis of the human microbiome from four different regions of China and machine learning-based geographical inference.}, journal = {mSphere}, volume = {10}, number = {1}, pages = {e0067224}, pmid = {39699186}, issn = {2379-5042}, support = {2022YFC3302004//MOST | National Key Research and Development Program of China (NKPs)/ ; 2022D01C443//| Natural Science Foundation of Xinjiang Uygur Autonomous Region (Xinjiang Natural Science Foundation)/ ; //Visiting Research Fund for Teachers of Ordinary Undergraduate Universities in Shandong Province/ ; }, mesh = {Humans ; China ; *Microbiota/genetics ; *RNA, Ribosomal, 16S/genetics ; *Bacteria/classification/genetics/isolation &amp; purification ; Male ; Female ; Adult ; *Mouth/microbiology ; *Machine Learning ; *Skin/microbiology ; Middle Aged ; Nasal Cavity/microbiology ; Young Adult ; DNA, Bacterial/genetics ; Hand/microbiology ; Geography ; Phylogeny ; Sequence Analysis, DNA/methods ; }, abstract = {The human microbiome, the community of microorganisms that reside on and inside the human body, is critically important for health and disease. However, it is influenced by various factors and may vary among individuals residing in distinct geographic regions. In this study, 220 samples, consisting of sterile swabs from palmar skin and oral and nasal cavities were collected from Chinese Han individuals living in Shanghai, Chifeng, Kunming, and Urumqi, representing the geographic regions of east, northeast, southwest, and northwest China. The full-length 16S rRNA gene of the microbiota in each sample was sequenced using the PacBio single-molecule real-time sequencing platform, followed by clustering the sequences into operational taxonomic units (OTUs). The analysis revealed significant differences in microbial communities among the four regions. Cutibacterium was the most abundant bacterium in palmar samples from Shanghai and Kunming, Psychrobacter in Chifeng samples, and Psychrobacillus in Urumqi samples. Additionally, Streptococcus and Staphylococcus were the dominant bacteria in the oral and nasal cavities. Individuals from the four regions could be distinguished and predicted based on a model constructed using the random forest algorithm, with the predictive effect of palmar microbiota being better than that of oral and nasal cavities. The prediction accuracy using hypervariable regions (V3-V4 and V4-V5) was comparable with that of using the entire 16S rRNA. Overall, our study highlights the distinctiveness of the human microbiome in individuals living in these four regions. Furthermore, the microbiome can serve as a biomarker for geographic origin inference, which has immense application value in forensic science.IMPORTANCEMicrobial communities in human hosts play a significant role in health and disease, varying in species, quantity, and composition due to factors such as gender, ethnicity, health status, lifestyle, and living environment. The characteristics of microbial composition at various body sites of individuals from different regions remain largely unexplored. This study utilized single-molecule real-time sequencing technology to detect the entire 16S rRNA gene of bacteria residing in the palmar skin, oral, and nasal cavities of Han individuals from four regions in China. The composition and structure of the bacteria at these three body sites were well characterized and found to differ regionally. The results elucidate the differences in bacterial communities colonizing these body sites across different regions and reveal the influence of geographical factors on human bacteria. These findings not only contribute to a deeper understanding of the diversity and geographical distribution of human bacteria but also enrich the microbiome data of the Asian population for further studies.}, }
@article {pmid39697649, year = {2024}, author = {Aluthge, N and Adams, S and Davila, CA and Gocchi Carrasco, NR and Chiou, KS and Abadie, R and Bennett, SJ and Dombrowski, K and Major, AM and Valentín-Acevedo, A and West, JT and Wood, C and Fernando, SC}, title = {Gut microbiota profiling in injection drug users with and without HIV-1 infection in Puerto Rico.}, journal = {Frontiers in microbiology}, volume = {15}, number = {}, pages = {1470037}, pmid = {39697649}, issn = {1664-302X}, support = {R01 DA047823/DA/NIDA NIH HHS/United States ; }, abstract = {INTRODUCTION: The full extent of interactions between human immunodeficiency virus (HIV) infection, injection drug use, and the human microbiome is unclear. In this study, we examined the microbiomes of HIV-positive and HIV-negative individuals, both drug-injecting and non-injecting, to identify bacterial community changes in response to HIV and drug use. We utilized a well-established cohort of people who inject drugs in Puerto Rico, a region with historically high levels of injection drug use and an HIV incidence rate disproportionately associated with drug use.<br><br>METHODS: Using amplicon-based 16S rDNA sequencing, we identified amplicon sequence variants (ASVs) that demonstrated significant variations in the composition of microbial communities based on HIV status and drug use.<br><br>RESULTS AND DISCUSSION: Our findings indicate that the HIV-positive group exhibited a higher abundance of ASVs belonging to the genera Prevotella, Alloprevotella, Sutterella, Megasphaera, Fusobacterium, and Mitsuokella. However, Bifidobacteria and Lactobacillus ASVs were more abundant in injectors than in non-injectors. We examined the effect of drug use on the gut microbiome in both HIV-infected and non-infected patients, and found that multiple drug use significantly affected the microbial community composition. Analysis of differential of bacterial taxa revealed an enrichment of Bifidobacterium spp., Faecalibacterium spp., and Lactobacillus spp. in the multiple drug-injecting group. However, in the non-injecting group, Parabacteroides spp., Prevotella spp., Paraprevotella spp., Sutterella spp., and Lachnoclostridium spp. The presence of multiple drug-injecting groups was observed to be more prevalent. Our findings provide detailed insight into ASV-level changes in the microbiome in response to HIV and drug use, suggesting that the effect of HIV status and drug injection may have different effects on microbiome composition and in modulating gut bacterial populations.}, }
@article {pmid39695869, year = {2024}, author = {Rodriguez, J and Cordaillat-Simmons, M and Badalato, N and Berger, B and Breton, H and de Lahondès, R and Deschasaux-Tanguy, M and Desvignes, C and D'Humières, C and Kampshoff, S and Lavelle, A and Metwaly, A and Quijada, NM and Seegers, JFML and Udocor, A and Zwart, H and ,  and Maguin, E and Doré, J and Druart, C}, title = {Microbiome testing in Europe: navigating analytical, ethical and regulatory challenges.}, journal = {Microbiome}, volume = {12}, number = {1}, pages = {258}, pmid = {39695869}, issn = {2049-2618}, mesh = {Humans ; Europe ; *Feces/microbiology ; Microbiota ; Reproducibility of Results ; }, abstract = {BACKGROUND: In recent years, human microbiome research has flourished and has drawn attention from both healthcare professionals and general consumers as the human microbiome is now recognized as having a significant influence on human health. This has led to the emergence of companies offering microbiome testing services. Some of these services are sold directly to the consumer via companies' websites or via medical laboratory websites.<br><br>METHODOLOGY: In order to provide an overview of the consumer experience proposed by these microbiome testing services, one single faecal sample was sent to six different companies (five based in Europe and one based in the USA). Two out of the six testing kits were commercialized by medical laboratories, but without any requirement for a medical prescription. The analyses and reports received were discussed with a panel of experts (21 experts from 8 countries) during an online workshop.<br><br>RESULTS: This workshop led to the identification of several limitations and challenges related to these kits, including over-promising messages from the companies, a lack of transparency in the methodology used for the analysis and a lack of reliability of the results. The experts considered the interpretations and recommendations provided in the different reports to be premature due to the lack of robust scientific evidence and the analyses associated with the reports to be of limited clinical utility. The experts also discussed the grey areas surrounding the regulatory status of these test kits, including their positioning in the European market. The experts recommended a distinction between regulatory requirements based on the intended use or purpose of the kit: on the one hand, test kits developed to satisfy consumer curiosity, with a clear mention of this objective, and no mention of any disease or risk of disease, and on the other hand, in vitro&#xa0;diagnostic (IVD) CE-marked test kits, which could go deeper into the analysis and interpretation of samples, as such a report would be intended for trained healthcare professionals.<br><br>CONCLUSIONS: Recommendations or actions, specific to the context of use of microbiome testing kits, are listed to improve the quality and the robustness of these test kits to meet expectations of end users (consumers, patients and healthcare professionals). The need for standardization, robust scientific evidence, qualification of microbiome-based biomarkers and a clear regulatory status in Europe are the main issues that will require attention in the near future to align laboratory development with societal needs and thus foster translation into daily health practice.}, }
@article {pmid39695352, year = {2025}, author = {Moore, M and Whittington, HD and Knickmeyer, R and Azcarate-Peril, MA and Bruno-Bárcena, JM}, title = {Non-stochastic reassembly of a metabolically cohesive gut consortium shaped by N-acetyl-lactosamine-enriched fibers.}, journal = {Gut microbes}, volume = {17}, number = {1}, pages = {2440120}, pmid = {39695352}, issn = {1949-0984}, mesh = {Humans ; *Gastrointestinal Microbiome ; Infant ; *Bacteria/metabolism/classification/isolation &amp; purification/genetics ; Feces/microbiology ; Lactose/metabolism ; Dietary Fiber/metabolism ; Oligosaccharides/metabolism ; Amino Sugars ; }, abstract = {Diet is one of the main factors shaping the human microbiome, yet our understanding of how specific dietary components influence microbial consortia assembly and subsequent stability in response to press disturbances - such as increasing resource availability (feeding rate) - is still incomplete. This study explores the reproducible re-assembly, metabolic interplay, and compositional stability within microbial consortia derived from pooled stool samples of three healthy infants. Using a single-step packed-bed reactor (PBR) system, we assessed the reassembly and metabolic output of consortia exposed to lactose, glucose, galacto-oligosaccharides (GOS), and humanized GOS (hGOS). Our findings reveal that complex carbohydrates, especially those containing low inclusion (~1.25 gL[-1]) components present in human milk, such as N-acetyl-lactosamine (LacNAc), promote taxonomic, and metabolic stability under varying feeding rates, as shown by diversity metrics and network analysis. Targeted metabolomics highlighted distinct metabolic responses to different carbohydrates: GOS was linked to increased lactate, lactose to propionate, sucrose to butyrate, and CO2, and the introduction of bile salts with GOS or hGOS resulted in butyrate reduction and increased hydrogen production. This study validates the use of single-step PBRs for reliably studying microbial consortium stability and functionality in response to nutritional press disturbances, offering insights into the dietary modulation of microbial consortia and their ecological dynamics.}, }
@article {pmid39690351, year = {2024}, author = {Ullah, H and Hassan, SHA and Yang, Q and Salama, ES and Liu, P and Li, X}, title = {Dynamic interaction of antibiotic resistance between plant microbiome and organic fertilizers: sources, dissemination, and health risks.}, journal = {World journal of microbiology &amp; biotechnology}, volume = {41}, number = {1}, pages = {4}, pmid = {39690351}, issn = {1573-0972}, support = {lzujbky-2024-ey12//Fundamental Research Funds for the Central Universities/ ; }, mesh = {Animals ; Humans ; Agriculture/methods ; *Anti-Bacterial Agents/pharmacology ; *Bacteria/drug effects/genetics/classification ; Drug Resistance, Bacterial/drug effects/genetics ; *Fertilizers/analysis ; Gene Transfer, Horizontal ; *Manure/microbiology ; *Microbiota/drug effects ; *Plants/microbiology ; Sewage/microbiology ; Soil/chemistry ; *Soil Microbiology ; Wastewater/chemistry/microbiology ; }, abstract = {Antibiotic resistance is a global health problem driven by the irrational use of antibiotics in different areas (such as agriculture, animal farming, and human healthcare). Sub-lethal concentrations of antibiotic residues impose selective pressure on environmental, plant-associated, and human microbiome leading to the emergence of antibiotic-resistant bacteria (ARB). This review summarizes all sources of antibiotic resistance in agricultural soils (including manure, sewage sludge, wastewater, hospitals/pharmaceutical industry, and bioinoculants). The factors (such as the physicochemical properties of soil, root exudates, concentration of antibiotic exposure, and heavy metals) that facilitate the transmission of resistance in plant microbiomes are discussed. Potential solutions for effective measures and control of antibiotic resistance in the environment are also hypothesized. Manure exhibits the highest antibiotics load, followed by hospital and municipal WW. Chlortetracycline, tetracycline, and sulfadiazine have the highest concentrations in the manure. Antibiotic resistance from organic fertilizers is transmitted to the plant microbiome via horizontal gene transfer (HGT). Plant microbiomes serve as transmission routes of ARB and ARGS to humans. The ingestion of ARB leads to human health risks (such as ineffectiveness of medication, increased morbidity, and mortality).}, }
@article {pmid39690257, year = {2024}, author = {Tsuchida, S and Umemura, H and Iizuka, K and Yamamoto, H and Shimazaki, I and Shikata, E and Nakayama, T}, title = {Recent findings on metabolomics and the microbiome of oral bacteria involved in dental caries and periodontal disease.}, journal = {World journal of microbiology &amp; biotechnology}, volume = {41}, number = {1}, pages = {11}, pmid = {39690257}, issn = {1573-0972}, mesh = {Animals ; Humans ; *Bacteria/classification/metabolism/genetics/isolation &amp; purification ; Biofilms/growth &amp; development ; *Dental Caries/microbiology ; Metabolomics/methods ; *Microbiota ; *Mouth/microbiology ; *Periodontal Diseases/microbiology ; }, abstract = {Periodontal disease is characterized by bacterial toxins within the oral biofilm surrounding the teeth, leading to gingivitis and the gradual dissolution of the alveolar bone, which supports the teeth. Notably, symptoms in the early stages of the disease are often absent. Similarly, dental caries occurs when oral bacteria metabolize dietary sugars, producing acids that dissolve tooth enamel and dentin. These bacteria are commonly present in the oral cavity of most individuals. Metabolomics, a relatively recent addition to the "omics" research landscape, involves the comprehensive analysis of metabolites in vivo to elucidate pathological mechanisms and accelerate drug discovery. Meanwhile, the term "microbiome" refers to the collection of microorganisms within a specific environmental niche or their collective genomes. The human microbiome plays a critical role in health and disease, influencing a wide array of physiological and pathological processes. Recent advances in microbiome research have identified numerous bacteria implicated in dental caries and periodontal disease. Additionally, studies have uncovered various pathogenic factors associated with these microorganisms. This review focuses on recent findings in metabolomics and the microbiome, specifically targeting oral bacteria linked to dental caries and periodontal disease. We acknowledge the limitation of relying exclusively on the MEDLINE database via PubMed, while excluding other sources such as gray literature, conference proceedings, and clinical practice guidelines.}, }
@article {pmid39689342, year = {2024}, author = {Chircop, O and Jaggers, C and Spiteri, M and Schembri, A and Padovese, V}, title = {DOXY do, or DOXY Don't? Syphilis and doxycycline post-exposure prophylaxis: A case report.}, journal = {International journal of STD &amp; AIDS}, volume = {}, number = {}, pages = {9564624241308026}, doi = {10.1177/09564624241308026}, pmid = {39689342}, issn = {1758-1052}, abstract = {The resurgence of syphilis across Europe has led to a growing number of atypical cases, often characterised by varied symptoms that can delay diagnosis. We report the case of a young man who has sex with men (MSM), presenting with persistent headaches and swelling of the forehead suggestive of giant cell arteritis (GCA). Despite a recent negative syphilis test, further investigations confirmed the diagnosis of neurosyphilis. The patient had been using doxycycline post-exposure prophylaxis (DoxyPEP), which is suspected to have delayed the diagnosis by masking the typical antibody response. This case highlights concerns about DoxyPEP's impact on syphilis detection and disease progression. Further research is warranted to explore its effects on antimicrobial resistance, the human microbiome, and clinical outcomes.}, }
@article {pmid39688588, year = {2025}, author = {Jiang, H and Miao, X and Thairu, MW and Beebe, M and Grupe, DW and Davidson, RJ and Handelsman, J and Sankaran, K}, title = {Multimedia: multimodal mediation analysis of microbiome data.}, journal = {Microbiology spectrum}, volume = {13}, number = {2}, pages = {e0113124}, pmid = {39688588}, issn = {2165-0497}, support = {R01GM152744//HHS | NIH | National Institute of General Medical Sciences (NIGMS)/ ; T15 LM007359/LM/NLM NIH HHS/United States ; }, mesh = {Humans ; *Microbiota ; *Software ; Mediation Analysis ; Inflammatory Bowel Diseases/microbiology ; Gastrointestinal Microbiome ; Multimedia ; Metabolome ; }, abstract = {UNLABELLED: Mediation analysis has emerged as a versatile tool for answering mechanistic questions in microbiome research because it provides a statistical framework for attributing treatment effects to alternative causal pathways. Using a series of linked regressions, this analysis quantifies how complementary data relate to one another and respond to treatments. Despite these advances, existing software's rigid assumptions often result in users viewing mediation analysis as a black box. We designed the multimedia R package to make advanced mediation analysis techniques accessible, ensuring that statistical components are interpretable and adaptable. The package provides a uniform interface to direct and indirect effect estimation, synthetic null hypothesis testing, bootstrap confidence interval construction, and sensitivity analysis, enabling experimentation with various mediator and outcome models while maintaining a simple overall workflow. The software includes modules for regularized linear, compositional, random forest, hierarchical, and hurdle modeling, making it well-suited to microbiome data. We illustrate the package through two case studies. The first re-analyzes a study of the microbiome and metabolome of Inflammatory Bowel Disease patients, uncovering potential mechanistic interactions between the microbiome and disease-associated metabolites, not found in the original study. The second analyzes new data about the influence of mindfulness practice on the microbiome. The mediation analysis highlights shifts in taxa previously associated with depression that cannot be explained indirectly by diet or sleep behaviors alone. A gallery of examples and further documentation can be found at https://go.wisc.edu/830110.<br><br>IMPORTANCE: Microbiome studies routinely gather complementary data to capture different aspects of a microbiome's response to a change, such as the introduction of a therapeutic. Mediation analysis clarifies the extent to which responses occur sequentially via mediators, thereby supporting causal, rather than purely descriptive, interpretation. Multimedia is a modular R package with close ties to the wider microbiome software ecosystem that makes statistically rigorous, flexible mediation analysis easily accessible, setting the stage for precise and causally informed microbiome engineering.}, }
@article {pmid39684937, year = {2024}, author = {Balla, B and Illés, A and Tobiás, B and Pikó, H and Beke, A and Sipos, M and Lakatos, P and Kósa, JP}, title = {The Role of the Vaginal and Endometrial Microbiomes in Infertility and Their Impact on Pregnancy Outcomes in Light of Recent Literature.}, journal = {International journal of molecular sciences}, volume = {25}, number = {23}, pages = {}, pmid = {39684937}, issn = {1422-0067}, support = {2020-4.1.1.-TKP2020-MOLORKIV//Hungarian Ministry of Innovation and Technology/ ; }, mesh = {Humans ; Female ; *Vagina/microbiology ; Pregnancy ; *Microbiota ; *Endometrium/microbiology/metabolism ; *Pregnancy Outcome ; Dysbiosis/microbiology ; Infertility, Female/microbiology ; Infertility/microbiology ; }, abstract = {The Human Microbiome Project (HMP), initiated in 2007, aimed to gather comprehensive knowledge to create a genetic and metabolic map of human-associated microorganisms and their contribution to physiological states and predisposition to certain diseases. Research has revealed that the human microbiome is highly diverse and exhibits significant interpersonal variability; consequently, its exact impact on health remains unclear. With the development of next-generation sequencing (NGS) technologies, the broad spectrum of microbial communities has been better characterized. The lower female genital tract, particularly the vagina, is colonized by various bacterial species, with Lactobacillus spp. predominating. The upper female genital tract, especially the uterus, was long considered sterile. However, recent studies have identified a distinct endometrial microbiome. A Lactobacillus-dominated microbiome of the female genital tract is associated with favorable reproductive outcomes, including higher success rates in natural conception and assisted reproductive technologies (ART). Conversely, microbial imbalances, or dysbiosis, marked by reduced Lactobacilli as well as an increased diversity and abundance of pathogenic species (e.g., Gardnerella vaginalis or Prevotella spp.), are linked to infertility, implantation failure, and pregnancy complications such as miscarriage and preterm birth. Dysbiosis can impair the vaginal or endometrial mucosal barrier and also trigger pro-inflammatory responses, disrupting essential reproductive processes like implantation. Despite growing evidence supporting the associations between the microbiome of the female genital tract and certain gynecological and obstetric conditions, clear microbial biomarkers have yet to be identified, and there is no consensus on the precise composition of a normal or healthy microbiome. The lack of standardized protocols and biomarkers limits the routine use of microbiome screening tests. Therefore, larger patient cohorts are needed to facilitate comparative studies and improve our understanding of the physiological microbiome profiles of the uterus and vagina, as well as how dysbiosis may influence clinical outcomes. Further research is required to refine diagnostic tools and develop personalized therapeutic strategies to improve fertility and pregnancy outcomes.}, }
@article {pmid39684310, year = {2024}, author = {Cominelli, G and Lonati, C and Pinto, D and Rinaldi, F and Franco, C and Favero, G and Rezzani, R}, title = {Melatonin Attenuates Ferritinophagy/Ferroptosis by Acting on Autophagy in the Liver of an Autistic Mouse Model BTBR T[+]Itpr3[tf]/J.}, journal = {International journal of molecular sciences}, volume = {25}, number = {23}, pages = {}, pmid = {39684310}, issn = {1422-0067}, support = {grants ex 60%//University of Brescia - Italy/ ; grant donation//FLAMMA S.p.A.- Italy/ ; }, mesh = {Animals ; *Melatonin/pharmacology ; Mice ; *Disease Models, Animal ; *Liver/metabolism/drug effects/pathology ; *Autophagy/drug effects ; *Ferroptosis/drug effects ; *Ferritins/metabolism ; Male ; Nuclear Receptor Coactivators/metabolism/genetics ; Microtubule-Associated Proteins/metabolism/genetics ; Autistic Disorder/metabolism/drug therapy/pathology ; Autism Spectrum Disorder/metabolism/drug therapy ; }, abstract = {Autism spectrum disorders (ASDs) are a pool of neurodevelopment disorders in which social impairment is the main symptom. Presently, there are no definitive medications to cure the symptoms but the therapeutic strategies that are taken ameliorate them. The purpose of this study was to investigate the effects of melatonin (MLT) in treating ASDs using an autistic mouse model BTBR T[+]Itpr3[tf]/J (BTBR). We evaluated the hepatic cytoarchitecture and some markers of autophagy, ferritinophagy/ferroptosis, in BTBR mice treated and not-treated with MLT. The hepatic morphology and the autophagy and ferritinophagy/ferroptosis pathways were analyzed by histological, immunohistochemical, and Western blotting techniques. We studied p62 and microtubule-associated protein 1 light chain 3 B (LC3B) for evaluating the autophagy; nuclear receptor co-activator 4 (NCOA4) and long-chain-coenzyme synthase (ACSL4) for monitoring ferritinophagy/ferroptosis. The liver of BTBR mice revealed that the hepatocytes showed many cytoplasmic inclusions recognized as Mallory-Denk bodies (MDBs); the expression and levels of p62 and LC3B were downregulated, whereas ACSL4 and NCOA4 were upregulated, as compared to control animals. MLT administration to BTBR mice ameliorated liver damage and reduced the impairment of autophagy and ferritinophagy/ferroptosis. In conclusion, we observed that MLT alleviates liver damage in BTBR mice by improving the degradation of intracellular MDBs, promoting autophagy, and suppressing ferritinophagy/ferroptosis.}, }
@article {pmid39683635, year = {2024}, author = {Ouédraogo, LO and Deng, L and Ouattara, CA and Compaoré, A and Ouédraogo, M and Argaw, A and Lachat, C and Houpt, ER and Saidi, Q and Haerynck, F and Sonnenburg, J and Azad, MB and Tavernier, SJ and Bastos-Moreira, Y and Toe, LC and Dailey-Chwalibóg, T}, title = {Describing Biological Vulnerability in Small, Vulnerable Newborns in Urban Burkina Faso (DenBalo): Gut Microbiota, Immune System, and Breastmilk Assembly.}, journal = {Nutrients}, volume = {16}, number = {23}, pages = {}, pmid = {39683635}, issn = {2072-6643}, support = {INV-035474 &amp; INV-036154/GATES/Bill &amp; Melinda Gates Foundation/United States ; }, mesh = {Humans ; Burkina Faso ; Female ; Infant, Newborn ; *Gastrointestinal Microbiome ; *Milk, Human/immunology ; Prospective Studies ; *Vagina/microbiology/immunology ; *Immune System ; Pregnancy ; Breast Feeding ; Infant, Small for Gestational Age ; Adult ; }, abstract = {Background: Small vulnerable newborns (SVNs), including those born preterm, small for gestational age, or with low birth weight, are at higher risk of neonatal mortality and long-term health complications. Early exposure to maternal vaginal microbiota and breastfeeding plays a critical role in the development of the neonatal microbiota and immune system, especially in low-resource settings like Burkina Faso, where neonatal mortality rates remain high. Objectives: The DenBalo study aims to investigate the role of maternal and neonatal factors, such as vaginal and gut microbiota, immune development, and early nutrition, in shaping health outcomes in SVNs and healthy infants. Methods: This prospective cohort observational study will recruit 141 mother-infant pairs (70 SVNs and 71 healthy controls) from four health centers in Bobo-Dioulasso, Burkina Faso. The mother-infant pairs will be followed for six months with anthropometric measurements and biospecimen collections, including blood, breast milk, saliva, stool, vaginal swabs, and placental biopsies. Multi-omics approaches, encompassing metagenomics, metabolomics, proteomics, and immune profiling, will be used to assess vaginal and gut microbiota composition and functionality, immune cell maturation, and cytokine levels at critical developmental stages. Conclusions: This study will generate comprehensive data on how microbiota, metabolomic, and proteomic profiles, along with immune system development, differ between SVNs and healthy infants. These findings will guide targeted interventions to improve neonatal health outcomes and reduce mortality, particularly in vulnerable populations.}, }
@article {pmid39682776, year = {2024}, author = {Kim, S and Rahim, MA and Tajdozian, H and Barman, I and Park, HA and Yoon, Y and Jo, S and Lee, S and Shuvo, MSH and Bae, SH and Lee, H and Ju, S and Park, CE and Kim, HK and Han, JH and Kim, JW and Yoon, SG and Kim, JH and Choi, YG and Lee, S and Seo, H and Song, HY}, title = {Clinical Potential of Novel Microbial Therapeutic LP51 Based on Xerosis-Microbiome Index.}, journal = {Cells}, volume = {13}, number = {23}, pages = {}, pmid = {39682776}, issn = {2073-4409}, support = {RS-2023-00219563//National Research Foundation of Korea/ ; P248400003//Korea Institute for Advancement of Technology/ ; }, mesh = {Humans ; Female ; *Microbiota/drug effects ; Double-Blind Method ; Adult ; Skin/microbiology/pathology ; Middle Aged ; }, abstract = {Xerosis, characterized by dry, rough skin, causes discomfort and aesthetic concerns, necessitating effective treatment. Traditional treatments often show limited efficacy, prompting the need for innovative therapies. This study highlights the efficacy of microbiome therapeutic LP51, derived from a healthy vaginal microbiome, in improving xerosis. A double-blind clinical trial involving 43 subjects with dry inner arm skin compared the effects of a 2.9% LP51 extract formulation to a placebo over 4 weeks. The LP51 group exhibited a significant increase in stratum corneum hydration (10.0 A.U.) compared to the placebo group (4.8 A.U.) and a 21.4% decrease in transepidermal water loss (TEWL), whereas the placebo group showed no significant change. LP51 also demonstrated benefits in enhancing skin hydration, improving the skin barrier, and exhibited anti-atopic, anti-inflammatory, and antioxidant properties. Safety was confirmed through in vitro cytotoxicity tests. These effects are attributed to the microbiome-safe component in LP51 and its role in improving xerosis, reflected by an increase in the xerosis-microbiome index, defined by the Firmicutes/Actinobacteria ratio. These findings position microbiome therapeutic LP51 as a promising novel treatment for xerosis.}, }
@article {pmid39682751, year = {2024}, author = {Seo, H and Kim, S and Beck, S and Song, HY}, title = {Perspectives on Microbiome Therapeutics in Infectious Diseases: A Comprehensive Approach Beyond Immunology and Microbiology.}, journal = {Cells}, volume = {13}, number = {23}, pages = {}, pmid = {39682751}, issn = {2073-4409}, support = {RS-2023-00219563//Ministry of Science and ICT/ ; P248400003//Korea Institute for Advancement of Technology/ ; Soonchunhyang University Research Fund//Soonchunhyang University Research Fund/ ; }, mesh = {Humans ; *Microbiota/immunology ; *Probiotics/therapeutic use ; *COVID-19/immunology/virology/therapy ; Communicable Diseases/microbiology/therapy/immunology ; SARS-CoV-2/immunology ; }, abstract = {Although global life expectancy has increased over the past 20 years due to advancements in managing infectious diseases, one-fifth of people still die from infections. In response to this ongoing threat, significant efforts are underway to develop vaccines and antimicrobial agents. However, pathogens evolve resistance mechanisms, complicating their control. The COVID-19 pandemic has underscored the limitations of focusing solely on the pathogen-killing strategies of immunology and microbiology to address complex, multisystemic infectious diseases. This highlights the urgent need for practical advancements, such as microbiome therapeutics, that address these limitations while complementing traditional approaches. Our review emphasizes key outcomes in the field, including evidence of probiotics reducing disease severity and insights into host-microbiome crosstalk that have informed novel therapeutic strategies. These findings underscore the potential of microbiome-based interventions to promote physiological function alongside existing strategies aimed at enhancing host immune responses and pathogen destruction. This narrative review explores microbiome therapeutics as next-generation treatments for infectious diseases, focusing on the application of probiotics and their role in host-microbiome interactions. While offering a novel perspective grounded in a cooperative defense system, this review also addresses the practical challenges and limitations in translating these advancements into clinical settings.}, }
@article {pmid39682542, year = {2024}, author = {Morales, C and Ballestero, L and Del Río, P and Barbero-Herranz, R and Olavarrieta, L and Gómez-Artíguez, L and Galeano, J and Avendaño-Ortiz, J and Basterra, J and Del Campo, R}, title = {Should the Faecal Microbiota Composition Be Determined to Certify a Faecal Donor?.}, journal = {Diagnostics (Basel, Switzerland)}, volume = {14}, number = {23}, pages = {}, pmid = {39682542}, issn = {2075-4418}, support = {XX//Mikrobiomik/ ; }, abstract = {BACKGROUND/OBJECTIVES: Faecal microbiota transplantation (FMT) is considered a safe and effective therapy for recurrent Clostridioides difficile infection. It is the only current clinical indication for this technique, although numerous clinical research studies and trials propose its potential usefulness for treating other pathologies. Donor selection is a very rigorous process, based on a personal lifestyle interview and the absence of known pathogens in faeces and serum, leading to only a few volunteers finally achieving the corresponding certification. However, despite the high amount of data generated from the ongoing research studies relating microbiota and health, there is not yet a consensus defining what is a "healthy" microbiota. To date, knowledge of the composition of the microbiota is not a requirement to be a faecal donor. The aim of this work was to evaluate whether the analysis of the composition of the microbiota by massive sequencing of 16S rDNA could be useful in the selection of the faecal donors.<br><br>METHODS: Samples from 10 certified donors from Mikrobiomik Healthcare Company were collected and sequenced using 16S rDNA in a MiSeq (Illumina) platform. Alpha (Chao1 and Shannon indices) and beta diversity (Bray-Curtis) were performed using the bioinformatic web server Microbiome Analyst. The differences in microbial composition at the genera and phyla levels among the donors were evaluated.<br><br>RESULTS: The microbial diversity metric by alpha diversity indexes showed that most donors exhibited a similar microbial diversity and richness, whereas beta diversity by 16S rDNA sequencing revealed significant inter-donor differences, with a more stable microbial composition over time in some donors. The phyla Bacillota and Bacteroidota were predominant in all donors, while the density of other phyla, such as Actinomycota and Pseudomonota, varied among individuals. Each donor exhibited a characteristic genera distribution pattern; however, it was possible to define a microbiome core consisting of the genera Agathobacter, Eubacterium, Bacteroides, Clostridia UCG-014 and Akkermansia. Conclusions: The results suggest that donor certification does not need to rely exclusively on their microbiota composition, as it is unique to each donor. While one donor showed greater microbial diversity and richness, clear criteria for microbial normality and health have yet to be established. Therefore, donor certification should focus more on clinical and lifestyle aspects.}, }
@article {pmid39681696, year = {2024}, author = {Joos, R and Boucher, K and Lavelle, A and Arumugam, M and Blaser, MJ and Claesson, MJ and Clarke, G and Cotter, PD and De Sordi, L and Dominguez-Bello, MG and Dutilh, BE and Ehrlich, SD and Ghosh, TS and Hill, C and Junot, C and Lahti, L and Lawley, TD and Licht, TR and Maguin, E and Makhalanyane, TP and Marchesi, JR and Matthijnssens, J and Raes, J and Ravel, J and Salonen, A and Scanlan, PD and Shkoporov, A and Stanton, C and Thiele, I and Tolstoy, I and Walter, J and Yang, B and Yutin, N and Zhernakova, A and Zwart, H and ,  and Doré, J and Ross, RP}, title = {Author Correction: Examining the healthy human microbiome concept.}, journal = {Nature reviews. Microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41579-024-01145-8}, pmid = {39681696}, issn = {1740-1534}, support = {P30 ES005022/ES/NIEHS NIH HHS/United States ; }, }
@article {pmid39676876, year = {2024}, author = {Bhatnagar, K and Jha, K and Dalal, N and Patki, N and Gupta, G and Kumar, A and Kumar, A and Chaudhary, S}, title = {Exploring micronutrients and microbiome synergy: pioneering new paths in cancer therapy.}, journal = {Frontiers in immunology}, volume = {15}, number = {}, pages = {1442788}, pmid = {39676876}, issn = {1664-3224}, mesh = {Humans ; *Micronutrients/therapeutic use ; *Gastrointestinal Microbiome/immunology ; *Neoplasms/immunology/therapy/microbiology ; Animals ; Probiotics/therapeutic use ; Prebiotics/administration &amp; dosage ; Dysbiosis/therapy ; }, abstract = {The human microbiome is the complex ecosystem consisting of trillions of microorganisms that play a key role in developing the immune system and nutrient metabolism. Alterations in the gut microbiome have been linked to cancer initiation, progression, metastasis, and response to treatment. Accumulating evidence suggests that levels of vitamins and minerals influence the gut environment and may have implications for cancer risk and progression. Bifidobacterium has been reported to reduce the colorectal cancer risk by binding to free iron. Additionally, zinc ions have been shown to activate the immune cells and enhance the effectiveness of immunotherapy. Higher selenium levels have been associated with a reduced risk of several cancers, including colorectal cancer. In contrast, enhanced copper uptake has been implicated in promoting cancer progression, including colon cancer. The interaction between cancer and gut bacteria, as well as dysbiosis impact has been studied in animal models. The interplay between prebiotics, probiotics, synbiotics, postbiotics and gut bacteria in cancer offers the diverse physiological benefits. We also explored the particular probiotic formulations like VSL#3, Prohep, Lactobacillus rhamnosus GG (LGG), etc., for their ability to modulate immune responses and reduce tumor burden in preclinical models. Targeting the gut microbiome through antibiotics, bacteriophage, microbiome transplantation-based therapies will offer a new perspective in cancer research. Hence, to understand this interplay, we outline the importance of micronutrients with an emphasis on the immunomodulatory function of the microbiome and highlight the microbiome's potential as a target for precision medicine in cancer treatment.}, }
@article {pmid39675162, year = {2025}, author = {Skurnik, M}, title = {Scholarly discussion on the classification and electron microscopy analysis of lytic phage EC BD.}, journal = {International journal of food microbiology}, volume = {429}, number = {}, pages = {111012}, doi = {10.1016/j.ijfoodmicro.2024.111012}, pmid = {39675162}, issn = {1879-3460}, }
@article {pmid39662756, year = {2024}, author = {Hodgkiss, R and Acharjee, A}, title = {Unravelling metabolite-microbiome interactions in inflammatory bowel disease through AI and interaction-based modelling.}, journal = {Biochimica et biophysica acta. Molecular basis of disease}, volume = {1871}, number = {3}, pages = {167618}, doi = {10.1016/j.bbadis.2024.167618}, pmid = {39662756}, issn = {1879-260X}, abstract = {Inflammatory Bowel Diseases (IBDs) are chronic inflammatory disorders of the gastrointestinal tract and colon affecting approximately 7 million individuals worldwide. The knowledge of specific pathology and aetiological mechanisms leading to IBD is limited, however a reduced immune system, antibiotic use and reserved diet may initiate symptoms. Dysbiosis of the gut microbiome, and consequently a varied composition of the metabolome, has been extensively linked to these risk factors and IBD. Metagenomic sequencing and liquid-chromatography mass spectrometry (LC-MS) of N = 220 fecal samples by Fransoza et al., provided abundance data on microbial genera and metabolites for use in this study. Identification of differentially abundant microbes and metabolites was performed using a Wilcoxon test, followed by feature selection of random forest (RF), gradient-boosting (XGBoost) and least absolute shrinkage operator (LASSO) models. The performance of these features was then validated using RF models on the Human Microbiome Project 2 (HMP2) dataset and a microbial community (MICOM) model was utilised to predict and interpret the interactions between key microbes and metabolites. The Flavronifractor genus and microbes of the families Lachnospiraceae and Oscillospiraceae were found differential by all models. Metabolic pathways commonly influenced by such microbes in IBD were CoA biosynthesis, bile acid metabolism and amino acid production and degradation. This study highlights distinct interactive microbiome and metabolome profiles within IBD and the highly potential pathways causing disease pathology. It therefore paves way for future investigation into new therapeutic targets and non-invasive diagnostic tools for IBD.}, }
@article {pmid39657723, year = {2024}, author = {Sinkko, H and Olah, P and Yang, Y and Maia, G and Barrientos-Somarribas, M and Rádai, Z and Mäenpää, K and Sorratto, T and Salava, A and Lauerma, A and Barker, J and Ranki, A and Homey, B and Andersson, B and Fyhrquist, N and Alenius, H and , }, title = {Taxonomic and functional profiling of skin microbiome in psoriasis.}, journal = {The British journal of dermatology}, volume = {}, number = {}, pages = {}, doi = {10.1093/bjd/ljae471}, pmid = {39657723}, issn = {1365-2133}, }
@article {pmid39657633, year = {2024}, author = {Yang, W and Wu, K and Chen, H and Huang, J and Yu, Z}, title = {Emerging role of rare earth elements in biomolecular functions.}, journal = {The ISME journal}, volume = {}, number = {}, pages = {}, doi = {10.1093/ismejo/wrae241}, pmid = {39657633}, issn = {1751-7370}, abstract = {The importance of rare earth elements is increasingly recognized due to the increased demand for their mining and separation. This demand is driving research on the biology of rare earth elements. Biomolecules associated with rare earth elements include rare earth element-dependent enzymes (methanol dehydrogenase XoxF, ethanol dehydrogenase ExaF/PedH), rare earth element-binding proteins, and the relevant metallophores. Traditional (chemical) separation methods for rare earth elements harvesting and separation are typically inefficient, while causing environmental problems, whereas bioharvesting, potentially, offers more efficient, more green platforms. Here, we review the current state of research on the biological functions of rare earth element-dependent biomolecules, and the characteristics of the relevant proteins, including the specific amino acids involved in rare earth metal binding. We also provide an outlook at strategies for further understanding of biological processes and the potential applications of rare earth element-dependent enzymes and other biomolecules.}, }
@article {pmid39654676, year = {2024}, author = {Han, H and Choi, YH and Kim, SY and Park, JH and Chung, J and Na, HS}, title = {Optimizing microbiome reference databases with PacBio full-length 16S rRNA sequencing for enhanced taxonomic classification and biomarker discovery.}, journal = {Frontiers in microbiology}, volume = {15}, number = {}, pages = {1485073}, pmid = {39654676}, issn = {1664-302X}, abstract = {BACKGROUND: The study of the human microbiome is crucial for understanding disease mechanisms, identifying biomarkers, and guiding preventive measures. Advances in sequencing platforms, particularly 16S rRNA sequencing, have revolutionized microbiome research. Despite the benefits, large microbiome reference databases (DBs) pose challenges, including computational demands and potential inaccuracies. This study aimed to determine if full-length 16S rRNA sequencing data produced by PacBio could be used to optimize reference DBs and be applied to Illumina V3-V4 targeted sequencing data for microbial study.<br><br>METHODS: Oral and gut microbiome data (PRJNA1049979) were retrieved from NCBI. DADA2 was applied to full-length 16S rRNA PacBio data to obtain amplicon sequencing variants (ASVs). The RDP reference DB was used to assign the ASVs, which were then used as a reference DB to train the classifier. QIIME2 was used for V3-V4 targeted Illumina data analysis. BLAST was used to analyze alignment statistics. Linear discriminant analysis Effect Size (LEfSe) was employed for discriminant analysis.<br><br>RESULTS: ASVs produced by PacBio showed coverage of the oral microbiome similar to the Human Oral Microbiome Database. A phylogenetic tree was trimmed at various thresholds to obtain an optimized reference DB. This established method was then applied to gut microbiome data, and the optimized gut microbiome reference DB provided improved taxa classification and biomarker discovery efficiency.<br><br>CONCLUSION: Full-length 16S rRNA sequencing data produced by PacBio can be used to construct a microbiome reference DB. Utilizing an optimized reference DB can increase the accuracy of microbiome classification and enhance biomarker discovery.}, }
@article {pmid39651993, year = {2024}, author = {Poncet, R and Gargominy, O}, title = {In the Shadow of Medicine: The Glaring Absence of Occurrence Records of Human-Hosted Biodiversity.}, journal = {Online journal of public health informatics}, volume = {16}, number = {}, pages = {e60140}, pmid = {39651993}, issn = {1947-2579}, abstract = {Microbial diversity is vast, with bacteria playing a crucial role in human health. However, occurrence records (location, date, observer, and host interaction of human-associated bacteria) remain scarce. This lack of information hinders our understanding of human-microbe relationships and disease prevention. In this study, we show that existing solutions such as France's Système d'Information sur le Patrimoine Naturel framework, can be used to efficiently collect and manage occurrence data on human-associated bacteria. This user-friendly system allows medical personnel to easily share and access data on bacterial pathogens. By adopting similar national infrastructures and treating human-associated bacteria as biodiversity data, we can significantly improve public health management and research, and our understanding of the One Health concept, which emphasizes the interconnectedness of human, animal, and environmental health.}, }
@article {pmid39648582, year = {2024}, author = {Burton, JP and Kofoed, RH and Rust, R}, title = {Science around the world.}, journal = {Trends in molecular medicine}, volume = {30}, number = {3}, pages = {197-199}, doi = {10.1016/j.molmed.2024.01.008}, pmid = {39648582}, issn = {1471-499X}, }
@article {pmid39647502, year = {2025}, author = {Porcari, S and Mullish, BH and Asnicar, F and Ng, SC and Zhao, L and Hansen, R and O'Toole, PW and Raes, J and Hold, G and Putignani, L and Hvas, CL and Zeller, G and Koren, O and Tun, H and Valles-Colomer, M and Collado, MC and Fischer, M and Allegretti, J and Iqbal, T and Chassaing, B and Keller, J and Baunwall, SM and Abreu, M and Barbara, G and Zhang, F and Ponziani, FR and Costello, SP and Paramsothy, S and Kao, D and Kelly, C and Kupcinskas, J and Youngster, I and Franceschi, F and Khanna, S and Vehreschild, M and Link, A and De Maio, F and Pasolli, E and Miguez, AB and Brigidi, P and Posteraro, B and Scaldaferri, F and Stojanovic, MR and Megraud, F and Malfertheiner, P and Masucci, L and Arumugam, M and Kaakoush, N and Segal, E and Bajaj, J and Leong, R and Cryan, J and Weersma, RK and Knight, R and Guarner, F and Shanahan, F and Cani, PD and Elinav, E and Sanguinetti, M and de Vos, WM and El-Omar, E and Dorè, J and Marchesi, J and Tilg, H and Sokol, H and Segata, N and Cammarota, G and Gasbarrini, A and Ianiro, G}, title = {International consensus statement on microbiome testing in clinical practice.}, journal = {The lancet. Gastroenterology &amp; hepatology}, volume = {10}, number = {2}, pages = {154-167}, doi = {10.1016/S2468-1253(24)00311-X}, pmid = {39647502}, issn = {2468-1253}, mesh = {Humans ; *Gastrointestinal Microbiome ; *Consensus ; }, abstract = {There is growing interest in the potential exploitation of the gut microbiome as a diagnostic tool in medicine, but evidence supporting its clinical usefulness is scarce. An increasing number of commercial providers offer direct-to-consumer microbiome diagnostic tests without any consensus on their regulation or any proven value in clinical practice, which could result in considerable waste of individual and health-care resources and potential drawbacks in the clinical management of patients. We convened an international multidisciplinary expert panel to standardise best practices of microbiome testing for clinical implementation, including recommendations on general principles and minimum requirements for their provision, indications, pre-testing protocols, method of analyses, reporting of results, and potential clinical value. We also evaluated current knowledge gaps and future directions in this field. We aimed to establish a framework to regulate the provision of microbiome testing and minimise the use of inappropriate tests and pave the way for the evidence-based development and use of human microbiome diagnostics in clinical medicine.}, }
@article {pmid39639265, year = {2024}, author = {Ma, ZS}, title = {Revisiting microgenderome: detecting and cataloguing sexually unique and enriched species in human microbiomes.}, journal = {BMC biology}, volume = {22}, number = {1}, pages = {284}, pmid = {39639265}, issn = {1741-7007}, mesh = {Humans ; Female ; Male ; *Microbiota ; *Sex Characteristics ; Species Specificity ; }, abstract = {BACKGROUND: Microgenderome or arguably more accurately microsexome refers to studies on sexual dimorphism of human microbiomes aimed at investigating bidirectional interactions between human microbiomes, sex hormones, and immune systems. It is important because of its implications to disease susceptibility and therapy, in which men and women demonstrate divergence in many diseases especially autoimmune diseases. In a previous report [1], we presented analyses of several key ecological aspects of microgenderome by leveraging the large datasets of the HMP (human microbiome project) but failed to offer species-level composition differences such as sexually unique species (US) and enriched species (ES). Existing approaches, for such tasks, including differential species relative abundance analysis and differential network analysis, possess certain limitations given that virtually all rely on species abundance alone or are univariate, while ignoring species distribution information across samples. Obviously, it is both species abundance and distribution that shape/drive the structure and dynamics of human microbiomes, and both should be equally responsible for the universal heterogeneity of microbiomes including the sexual dimorphism.<br><br>RESULTS: Here, we fill the gap by taking advantages of a recently developed computational algorithm, species specificity, and specificity diversity (SSD) framework (refer to the companion article) to reanalyze the HMP and complementary seminovaginal microbiome datasets. The SSD framework can randomly search and catalogue the sexually specific unique/enriched species with statistical rigor, guided by species specificity (a synthetic metric of abundance and distribution) and specificity diversity (SD). The SSD framework reveals that men seem to have more unique species than women in their gut and reproductive system microbiomes, but women seem to have more unique species than men in the airway, oral, and skin microbiomes, which is likely due to sexual dimorphism in the hormone and immune systems. We further investigate co-dependency and heterogeneity of those sexually unique/enriched species across 15 body sites, with core/periphery network analyses.<br><br>CONCLUSIONS: This study not only produced sexually unique/enriched species in the human microbiomes and analyzed their codependency and heterogeneity but also further validated the robustness of the SSD framework presented in the companion article, by performing all negative control tests based on the HMP gut microbiome samples.}, }
@article {pmid39626677, year = {2024}, author = {He, Z and Yu, J and Gong, J and Wu, J and Zong, X and Luo, Z and He, X and Cheng, WM and Liu, Y and Liu, C and Zhang, Q and Dai, L and Ding, T and Gao, B and Gharaibeh, RZ and Huang, J and Jobin, C and Lan, P}, title = {Campylobacter jejuni-derived cytolethal distending toxin promotes colorectal cancer metastasis.}, journal = {Cell host &amp; microbe}, volume = {32}, number = {12}, pages = {2080-2091.e6}, doi = {10.1016/j.chom.2024.11.006}, pmid = {39626677}, issn = {1934-6069}, mesh = {Animals ; *Bacterial Toxins/metabolism/genetics ; *Colorectal Neoplasms/pathology/microbiology ; *Campylobacter jejuni/genetics/metabolism ; Humans ; Mice ; *STAT3 Transcription Factor/metabolism ; *Neoplasm Metastasis ; Campylobacter Infections/microbiology ; Janus Kinase 2/metabolism/genetics ; Matrix Metalloproteinase 9/metabolism ; Cell Line, Tumor ; Signal Transduction ; Disease Models, Animal ; Female ; }, abstract = {Various forms of solid tumors harbor intracellular bacteria, but the physiological consequences of these microorganisms are poorly understood. We show that Campylobacter is significantly enriched in primary colorectal cancer (CRC) lesions from patients with metastasis. Campylobacter jejuni-derived cytolethal distending toxin (CDT) promotes CRC metastasis through JAK2-STAT3-MMP9 signaling in liver or pulmonary metastatic mice models, as confirmed in C. jejuni-infected human colonic tissue and CDT-treated colonic tumoroids from patients. Genetic deletion of cdtB (ΔcdtB) or purified CdtB protein demonstrates that the genotoxin is essential for C. jejuni's pro-metastatic property. In C.-jejuni-colonized mice, increased translocation of CDT-producing C. jejuni to extraintestinal implanted tumors potentially leads to accelerated metastasis of these tumors. Overall, these findings demonstrate that an intratumor-bacteria-derived genotoxin accelerates tumor metastasis, potentially opening a new diagnostic and therapeutic avenue for cancer management.}, }
@article {pmid39624165, year = {2024}, author = {Zhang, Y and Schluter, J and Zhang, L and Cao, X and Jenq, RR and Feng, H and Haines, J and Zhang, L}, title = {Review and revamp of compositional data transformation: A new framework combining proportion conversion and contrast transformation.}, journal = {Computational and structural biotechnology journal}, volume = {23}, number = {}, pages = {4088-4107}, pmid = {39624165}, issn = {2001-0370}, abstract = {Due to the development of next-generation sequencing technology and an increased appreciation of their role in modulating host immunity and their potential as therapeutic agents, the human microbiome has emerged as a key area of interest in various biological investigations of human health and disease. However, microbiome data present a number of statistical challenges not addressed by existing methods, such as the varying sequencing depth, the compositionality, and zero inflation. Solutions like scaling and transformation methods help to mitigate heterogeneity and release constraints, but often introduce biases and yield inconsistent results on the same data. To address these issues, we conduct a systematic review of compositional data transformation, with a particular focus on the connection and distinction of existing techniques. Additionally, we create a new framework that enables the development of new transformations by combining proportion conversion with contrast transformations. This framework includes well-known methods such as Additive Log Ratio (ALR) and Centered Log Ratio (CLR) as special cases. Using this framework, we develop two novel transformations-Centered Arcsine Contrast (CAC) and Additive Arcsine Contrast (AAC)-which show enhanced performance in scenarios with high zero-inflation. Moreover, our findings suggest that ALR and CLR transformations are more effective when zero values are less prevalent. This comprehensive review and the innovative framework provide microbiome researchers with a significant direction to enhance data transformation procedures and improve analytical outcomes.}, }
@article {pmid39621633, year = {2024}, author = {Martins, FP and Andrade-Silva, J and Teixeira, BL and Ferrari, A and Christoff, AP and Cruz, GNF and Paladino, FV and de Oliveira, LFV and Hernandes, C}, title = {Oral microbiome test as an alternative diagnostic tool for gastric alterations: A prospective, bicentric cross-sectional study.}, journal = {PloS one}, volume = {19}, number = {12}, pages = {e0314660}, pmid = {39621633}, issn = {1932-6203}, mesh = {Humans ; Cross-Sectional Studies ; Female ; Male ; Middle Aged ; *Mouth/microbiology ; Prospective Studies ; Adult ; *Microbiota ; Brazil ; Aged ; Stomach/microbiology ; Bacteria/genetics/isolation &amp; purification/classification ; Stomach Diseases/microbiology/diagnosis ; }, abstract = {The human microbiome plays a pivotal role in influencing various physiological processes and maintaining overall well-being, including the gastric system. Current diagnostic tests for gastric diseases often involve invasive procedures, sampling limitations, and medication effects, leading to potential diagnostic errors and discomfort to patients. Considering the connection between oral and gastric microbiomes, this cross-sectional study aimed to assess the diagnostic potential of the oral bacterial profile in patients undergoing upper digestive endoscopy. Oral samples from 266 participants across two Brazilian sites (Belterra and Sao Paulo) were sequenced and subjected to bioinformatic analysis to identify microbiome composition across endoscopy outcome groups, exploring alpha and beta-diversity, richness, and differential abundance and prevalence. Prevotella, Haemophilus, Fusobacterium, Neisseria, and Streptococcus were the most abundant genera observed. No significant associations were found between alpha diversity profiles and endoscopy outcomes; beta diversity analyses similarly showed no correlations. Overall, the study did not establish the oral microbiome as a reliable marker for gastric health, underscoring the necessity for broader studies in the development of non-invasive diagnostic tests.}, }
@article {pmid39619727, year = {2024}, author = {Sawan, HM and Shroukh, W and Abutaima, R and Al Omari, SM and Abdel-Qader, DH and Binsuwaidan, R}, title = {Impact of Jordanian Pharmacists' Knowledge of the Human Microbiome: Has the Practice of Antibiotics and Probiotics Dispensing Been Affected? A Cross-Sectional Study.}, journal = {Infection and drug resistance}, volume = {17}, number = {}, pages = {5203-5214}, pmid = {39619727}, issn = {1178-6973}, abstract = {OBJECTIVE: This study aimed to assess Jordanian pharmacists' knowledge of the human microbiome and the impact of their knowledge on their attitudes and practices toward antibiotics and probiotics.<br><br>METHODS: A self-administered survey was designed after reviewing the literature. Participants' demographics were collected, and questions to evaluate pharmacists' knowledge, attitudes, and practices toward antibiotic and probiotic dispensing were asked. The data were analyzed using the Statistical Package for the Social Sciences V.26. Pearson correlations and one-way ANOVA were employed to calculate the significance of knowledge, attitudes, and practices. Statistical significance was considered at p < 0.05.<br><br>RESULTS: Of the 333 respondents, around 75% (n=250) had a high level of general knowledge regarding the human gut microbiome. Almost equal proportions of participants had either intermediate or high levels of knowledge about the role of gut bacteria in health (n=164, 49.2%) (n=166, 49.8%), respectively, while almost two-thirds had an intermediate level of knowledge of the role of gut bacteria in disease (n=197, 59.2%). More than half of the participants had a positive attitude toward antibiotics, probiotics, and the human microbiome (n=179, 53.8%), and the majority (n=239, 71.8%) had an intermediate level of practice with them. There was a significant positive correlation between pharmacists' general knowledge of the human microbiome and their positive attitudes (r=0.306, p < 0.01) and practices (r=0.331, p < 0.01) toward antibiotics and probiotics.<br><br>CONCLUSION: Study results raise the importance of interventional educational measures to promote healthcare professionals' knowledge of the human microbiome and their potential beneficence on pharmacists' attitudes and practices regarding antibiotics and probiotics dispensing. The results also denote the urgent need for probiotics' clinical guidelines to ensure practice uniformity.}, }
@article {pmid39614246, year = {2024}, author = {Marín-Sánchez, N and Paredes, R and Borgognone, A}, title = {Exploring potential associations between the human microbiota and reservoir of latent HIV.}, journal = {Retrovirology}, volume = {21}, number = {1}, pages = {21}, pmid = {39614246}, issn = {1742-4690}, support = {847943//European Union's Horizon 2020 Research and Innovation/ ; }, mesh = {Humans ; *HIV Infections/virology/microbiology/immunology ; *Virus Latency ; *HIV-1/physiology ; *Microbiota ; *Gastrointestinal Microbiome ; Virus Replication ; Disease Reservoirs/virology/microbiology ; }, abstract = {BACKGROUND: The rapid establishment and persistence of latent HIV-1 reservoirs is one of the main obstacles towards an HIV cure. While antiretroviral therapy supresses viral replication, it does not eradicate the latent reservoir of HIV-1-infected cells. Recent evidence suggests that the human microbiome, particularly the gut microbiome, may have the potential to modulate the HIV-1 reservoir. However, literature is limited and the exact mechanisms underlying the role of the microbiome in HIV immunity and potential regulation of the viral reservoir remain poorly understood.<br><br>RESULTS: Here, we review updated knowledge on the associations between the human microbiome and HIV reservoir across different anatomical sites, including the gut, the lungs and blood. We provide an overview of the predominant taxa associated with prominent microbiome changes in the context of HIV infection. Based on the current evidence, we summarize the main study findings, with specific focus on consistent bacterial and related byproduct associations. Specifically, we address the contribution of immune activation and inflammatory signatures on HIV-1 persistence. Furthermore, we discuss possible scenarios by which bacterial-associated inflammatory mediators, related metabolites and host immune signatures may modulate the HIV reservoir size. Finally, we speculate on potential implications of microbiome-based therapeutics for future HIV-1 cure strategies, highlighting challenges and limitations inherent in this research field.<br><br>CONCLUSIONS: Despite recent advances, this review underscores the need for further research to deepen the understanding of the complex interplay between the human microbiome and HIV reservoir. Further integrative multi-omics assessments and functional studies are crucial to test the outlined hypothesis and to identify potential therapeutic targets ultimately able to achieve an effective cure for HIV.}, }
@article {pmid39614169, year = {2024}, author = {Tang, H and Du, S and Niu, Z and Zhang, D and Tang, Z and Chen, H and Chen, Z and Zhang, M and Xu, Y and Sun, Y and Fu, X and Norback, D and Shao, J and Zhao, Z}, title = {Nasal, dermal, oral and indoor dust microbe and their interrelationship in children with allergic rhinitis.}, journal = {BMC microbiology}, volume = {24}, number = {1}, pages = {505}, pmid = {39614169}, issn = {1471-2180}, mesh = {Humans ; *Dust/analysis ; Male ; Child ; Female ; *Rhinitis, Allergic/microbiology ; Case-Control Studies ; *RNA, Ribosomal, 16S/genetics ; *Bacteria/classification/isolation &amp; purification/genetics ; *Skin/microbiology ; *Mouth/microbiology ; *Microbiota ; Nasal Cavity/microbiology ; Air Pollution, Indoor/analysis ; Child, Preschool ; Metagenomics/methods ; Nose/microbiology ; }, abstract = {BACKGROUND: Allergic rhinitis (AR) subjects might have their microenvironment changed due to pathogenesis and living environment. Whether the nasal microbe in AR children differs from healthy subjects and how it interplays with dermal, oral and indoor dust microbe needs to be elucidated.<br><br>METHODS: In this case-control study, we analyzed and compared the bacterial characterization and associations in nasal, dermal, oral swab samples and dust samples in 62 children with physician-diagnosed AR(cases) and 51 age- and gender-matched healthy ones with no history of allergic diseases(controls). Full-length 16S rRNA sequencing(swabs) and shotgun metagenomics(dust) were applied. Bacterial diversity, composition, abundance difference characteristics and fast expectation-maximization for microbial source tracking(FEAST) analysis were performed and compared between cases and controls.<br><br>RESULTS: The &#x3b1;-diversity of dust microorganisms in AR was lower than that in control group (P&#x2009;=&#x2009;0.034), and the &#x3b2;-diversity indices of microorganisms in nasal cavity (P&#x2009;=&#x2009;0.020), skin (P&#x2009;=&#x2009;0.001) and dust (P&#x2009;=&#x2009;0.004) were significantly different from those in control group. At species levels, a total of 10, 15, 12, and 15 bacterial species were differentially enriched in either cases or controls in nasal, dermal, oral, and dust samples, respectively(Linear Discriminant Analysis(LDA) score&#x2009;>&#x2009;2, P&#x2009;<&#x2009;0.05). Staphylococcus epidermidis was the single species simultaneously more abundant in nasal, dermal and dust samples in AR children. By FEAST analysis, 8.85% and 10.11% of S. epidermidis in AR dermal and dust samples came from nasal cavity. These proportions were significantly higher than those in controls (2.70% and 3.86%) (P&#x2009;<&#x2009;0.05). The same significantly higher transfer proportions(P&#x2009;<&#x2009;0.05) were observed for Staphylococcus aureus enriched in the nasal cavity in AR children. Classification models by random forest regression at species levels showed, bacterial species enriched in indoor dust, nasal and dermal samples had substantial power in distinguishing AR children from healthy ones, with the highest power in the dust samples (AUC&#x2009;=&#x2009;0.88) followed by nasal(AUC&#x2009;=&#x2009;0.81) and dermal ones(AUC&#x2009;=&#x2009;0.80).<br><br>CONCLUSIONS: Our study presented the microbial enrichment characteristics in AR children both in the living environment(dust) and body sites exposed to environment through inhalation(nasal cavity), contact(skin) and ingestion(oral cavity) pathways, respectively. Nasal S.epidermidis and S.aureus had dominant influences on dust and other body sites in AR children.}, }
@article {pmid39607341, year = {2024}, author = {Merk, LN and Shur, AS and Jena, S and Munoz, J and Brubaker, DK and Murray, RM and Green, LN}, title = {Diagnostic and Therapeutic Microbial Circuit with Application to Intestinal Inflammation.}, journal = {ACS synthetic biology}, volume = {13}, number = {12}, pages = {3885-3896}, doi = {10.1021/acssynbio.3c00668}, pmid = {39607341}, issn = {2161-5063}, mesh = {*Escherichia coli ; Humans ; *Probiotics/therapeutic use ; *Interleukin-22 ; Interleukins/metabolism/genetics ; Tetrathionic Acid/metabolism ; Inflammation/metabolism ; Gastrointestinal Microbiome/drug effects ; Inflammatory Bowel Diseases/therapy/metabolism ; Hemolysin Proteins/metabolism/genetics ; Tetracyclines ; }, abstract = {Bacteria genetically engineered to execute defined therapeutic and diagnostic functions in physiological settings can be applied to colonize the human microbiome, providing in situ surveillance and conditional disease modulation. However, many engineered microbes can only respond to single-input environmental factors, limiting their tunability, precision, and effectiveness as living diagnostic and therapeutic systems. For engineering microbes to improve complex chronic disorders such as inflammatory bowel disease, the bacteria must respond to combinations of stimuli in the proper context and time. This work implements a previously characterized split activator AND logic gate in the probiotic Escherichia coli strain Nissle 1917 (EcN). Our system can respond to two input signals: the inflammatory biomarker tetrathionate and a second input signal, anhydrotetracycline (aTc), for manual control. We report 4-6 fold induction with a minimal leak when the two chemical signals are present. We model the AND gate dynamics using chemical reaction networks and tune parameters in silico to identify critical perturbations that affect our circuit's selectivity. Finally, we engineer the optimized AND gate to secrete a therapeutic anti-inflammatory cytokine IL-22 using the hemolysin secretion pathway in the probiotic E. coli strain. We used a germ-free transwell model of the human gut epithelium to show that our engineering bacteria produce similar host cytokine responses compared to recombinant cytokine. Our study presents a scalable workflow to engineer cytokine-secreting microbes driven by logical signal processing. It demonstrates the feasibility of IL-22 derived from probiotic EcN with minimal off-target effects in a gut epithelial context.}, }
@article {pmid39602306, year = {2024}, author = {Pasolli, E and Mauriello, IE and Avagliano, M and Cavaliere, S and De Filippis, F and Ercolini, D}, title = {Bifidobacteriaceae diversity in the human microbiome from a large-scale genome-wide analysis.}, journal = {Cell reports}, volume = {43}, number = {12}, pages = {115027}, doi = {10.1016/j.celrep.2024.115027}, pmid = {39602306}, issn = {2211-1247}, mesh = {Humans ; *Phylogeny ; *Microbiota/genetics ; Metagenome ; Genome, Bacterial ; Genome-Wide Association Study ; Probiotics ; }, abstract = {We performed a large-scale genome-wide analysis aiming to investigate the prevalence and strain-level diversity of Bifidobacteriaceae species in the human microbiome. We considered 9,528 publicly available human metagenomes and integrated them with 1,192 isolate genomes from different sources. The prevalence and abundance of Bifidobacteriaceae species in humans was linked to multiple host characteristics: they were reduced in older people and enriched in populations characterized by Westernized lifestyles with geography-specific patterns. Phylogenetic analysis highlighted 110 Bifidobacteriaceae species-level genome bins (SGBs), with 32 found in humans and 8 in food and probiotic sources. Functional annotation revealed a great diversity in carbohydrate-active enzyme families across these SGBs. We found potential subspecies for most of the SGBs prevalent in humans and identified patterns driven by age and geography. We provided evidence that strains used in probiotics were rarely identified in humans, with the only exception represented by Bifidobacterium animalis. We finally evaluated that the abundance of Bifidobacteriaceae species exhibited moderate and variable capabilities to predict health status in case-control studies.}, }
@article {pmid39600874, year = {2024}, author = {Patjas, A and Jokiranta, TS and Kantele, A}, title = {Urinary tract infections: a retrospective cohort study of (mis)matching antimicrobial therapy and clinical outcome among Finnish adults.}, journal = {JAC-antimicrobial resistance}, volume = {6}, number = {6}, pages = {dlae188}, pmid = {39600874}, issn = {2632-1823}, abstract = {OBJECTIVES: With the global spread of antimicrobial resistance, treating urinary tract infections (UTIs) is becoming more challenging. Clinical data on UTI outcomes are scarce in cases with antimicrobial treatment mismatching the uropathogens' in vitro susceptibility profiles. We explored the association of (mis)matching antimicrobial treatment and clinical outcomes among patients with either ESBL-producing Enterobacterales (ESBL-PE) or non-ESBL-PE identified in urine samples.<br><br>PATIENTS AND METHODS: In 2015-2019, we recruited 18-65-year-old patients with laboratory-confirmed, community-acquired ESBL-PE (n&#x200a;=&#x200a;130) or non-ESBL-PE (n&#x200a;=&#x200a;187) UTI. Our study involved collecting data on in vitro susceptibility profiles, antimicrobial therapy (microbiological match/mismatch) and clinical outcomes, and a follow-up of relapses/reinfections.<br><br>RESULTS: Non-beta-lactam co-resistance was found more frequent among ESBL-PE than non-ESBL-PE isolates. The initial antimicrobial matched the in vitro susceptibility for 91.6% (164/179) of those with non-ESBL-PE and 46.9% (38/81) with ESBL-PE UTI (P&#x200a;<&#x200a;0.001). The clinical cure rates in the non-ESBL-PE and ESBL-PE UTI groups were 82.6% (142/172) and 62.2% (74/119) (P&#x200a;<&#x200a;0.001) for all, 87.3% (131/150) and 83.3% (30/36) for those treated with matching antimicrobials, and 33.3% (5/15) and 41.9% (18/43) for those given mismatching antimicrobials, respectively. Mismatching antimicrobial therapy was not associated with relapse/reinfection over the 3-month follow-up (P&#x200a;=&#x200a;0.943).<br><br>CONCLUSIONS: In our data, (mis)matching microbiological susceptibility is only partially associated with the clinical outcome of UTI: microbiological matching appears to predict clinical cure better than mismatching predicts clinical failure.}, }
@article {pmid39600755, year = {2024}, author = {Castro-Vidal, ZA and Mathew, F and Ibrahim, AA and Shubhangi, F and Cherian, RR and Choi, HK and Begum, A and Ravula, HK and Giri, H}, title = {The Role of Gastrointestinal Dysbiosis and Fecal Transplantation in Various Neurocognitive Disorders.}, journal = {Cureus}, volume = {16}, number = {10}, pages = {e72451}, pmid = {39600755}, issn = {2168-8184}, abstract = {This review explores the critical role of the human microbiome in neurological and neurodegenerative disorders, focusing on gut-brain axis dysfunction caused by dysbiosis, an imbalance in gut bacteria. Dysbiosis has been linked to diseases such as Alzheimer's disease, Parkinson's disease (PD), multiple sclerosis (MS), and stroke. The gut microbiome influences the central nervous system (CNS) through signaling molecules, including short-chain fatty acids, neurotransmitters, and metabolites, impacting brain health and disease progression. Emerging therapies, such as fecal microbiota transplantation (FMT), have shown promise in restoring microbial balance and alleviating neurological symptoms, especially in Alzheimer's and PD. Additionally, nutritional interventions such as probiotics, prebiotics, and specialized diets are being investigated for their ability to modify gut microbiota and improve patient outcomes. This review highlights the therapeutic potential of gut microbiota modulation but emphasizes the need for further clinical trials to establish the safety and efficacy of these interventions in neurological and mental health disorders.}, }
@article {pmid39596404, year = {2024}, author = {Wang, Z and Kaplan, RC and Burk, RD and Qi, Q}, title = {The Oral Microbiota, Microbial Metabolites, and Immuno-Inflammatory Mechanisms in Cardiovascular Disease.}, journal = {International journal of molecular sciences}, volume = {25}, number = {22}, pages = {}, pmid = {39596404}, issn = {1422-0067}, support = {K01 HL169019/HL/NHLBI NIH HHS/United States ; }, mesh = {Humans ; *Cardiovascular Diseases/microbiology/immunology/metabolism ; *Mouth/microbiology ; Inflammation/microbiology/metabolism/immunology ; Gastrointestinal Microbiome ; Microbiota ; Animals ; }, abstract = {Cardiovascular diseases (CVDs) remain a leading cause of global morbidity and mortality. Recent advancements in high-throughput omics techniques have enhanced our understanding of the human microbiome's role in the development of CVDs. Although the relationship between the gut microbiome and CVDs has attracted considerable research attention and has been rapidly evolving in recent years, the role of the oral microbiome remains less understood, with most prior studies focusing on periodontitis-related pathogens. In this review, we summarized previously reported associations between the oral microbiome and CVD, highlighting known CVD-associated taxa such as Porphyromonas gingivalis, Fusobacterium nucleatum, and Aggregatibacter actinomycetemcomitans. We also discussed the interactions between the oral and gut microbes. The potential mechanisms by which the oral microbiota can influence CVD development include oral and systemic inflammation, immune responses, cytokine release, translocation of oral bacteria into the bloodstream, and the impact of microbial-related products such as microbial metabolites (e.g., short-chain fatty acids [SCFAs], trimethylamine oxide [TMAO], hydrogen sulfide [H2S], nitric oxide [NO]) and specific toxins (e.g., lipopolysaccharide [LPS], leukotoxin [LtxA]). The processes driven by these mechanisms may contribute to atherosclerosis, endothelial dysfunction, and other cardiovascular pathologies. Integrated multi-omics methodologies, along with large-scale longitudinal population studies and intervention studies, will facilitate a deeper understanding of the metabolic and functional roles of the oral microbiome in cardiovascular health. This fundamental knowledge will support the development of targeted interventions and effective therapies to prevent or reduce the progression from cardiovascular risk to clinical CVD events.}, }
@article {pmid39595814, year = {2024}, author = {Belnap, N and Ramsey, K and Carvalho, ST and Nearman, L and Haas, H and Huentelman, M and Lee, K}, title = {Exploring the Frontier: The Human Microbiome's Role in Rare Childhood Neurological Diseases and Epilepsy.}, journal = {Brain sciences}, volume = {14}, number = {11}, pages = {}, pmid = {39595814}, issn = {2076-3425}, abstract = {Emerging research into the human microbiome, an intricate ecosystem of microorganisms residing in and on our bodies, reveals that it plays a pivotal role in maintaining our health, highlighting the potential for microbiome-based interventions to prevent, diagnose, treat, and manage a myriad of diseases. The objective of this review is to highlight the importance of microbiome studies in enhancing our understanding of rare genetic epilepsy and related neurological disorders. Studies suggest that the gut microbiome, acting through the gut-brain axis, impacts the development and severity of epileptic conditions in children. Disruptions in microbial composition can affect neurotransmitter systems, inflammatory responses, and immune regulation, which are all critical factors in the pathogenesis of epilepsy. This growing body of evidence points to the potential of microbiome-targeted therapies, such as probiotics or dietary modifications, as innovative approaches to managing epilepsy. By harnessing the power of the microbiome, we stand to develop more effective and personalized treatment strategies for children affected by this disease and other rare neurological diseases.}, }
@article {pmid39595625, year = {2024}, author = {Reshetova, M and Markin, P and Appolonova, S and Yunusov, I and Zolnikova, O and Bueverova, E and Dzhakhaya, N and Zharkova, M and Poluektova, E and Maslennikov, R and Ivashkin, V}, title = {Tryptophan Metabolites in the Progression of Liver Diseases.}, journal = {Biomolecules}, volume = {14}, number = {11}, pages = {}, pmid = {39595625}, issn = {2218-273X}, mesh = {Humans ; *Tryptophan/metabolism/blood ; Male ; Female ; Middle Aged ; Adult ; Kynurenine/analogs &amp; derivatives/metabolism/blood ; Disease Progression ; Liver Diseases, Alcoholic/metabolism/blood ; Serotonin/metabolism/blood ; Aged ; Fatty Liver/metabolism/blood ; Liver Cirrhosis/metabolism/blood ; }, abstract = {The aim of this study was to investigate the levels of various tryptophan metabolites in patients with alcoholic liver disease (ALD) and metabolic-associated fatty liver disease (MAFLD) at different stages of the disease. The present study included 44 patients diagnosed with MAFLD, 40 patients diagnosed with ALD, and 14 healthy individuals in the control group. The levels of tryptophan and its 16 metabolites (3-OH anthranilic acid, 5-hydroxytryptophan, 5-methoxytryptamine, 6-hydroxymelatonin, indole-3-acetic acid, indole-3-butyric, indole-3-carboxaldehyde, indole-3-lactic acid, indole-3-propionic acid, kynurenic acid, kynurenine, melatonin, quinolinic acid, serotonin, tryptamine, and xanthurenic acid) in the serum were determined via high-performance liquid chromatography and tandem mass spectrometry. In patients with cirrhosis resulting from MAFLD and ALD, there are significant divergent changes in the serotonin and kynurenine pathways of tryptophan catabolism as the disease progresses. All patients with cirrhosis showed a decrease in serotonin levels ([MAFLD]p = 0.038; [ALD]p < 0.001) and an increase in kynurenine levels ([MAFLD]p = 0.032; [ALD]p = 0.010). A negative correlation has been established between serotonin levels and the FIB-4 index (p < 0.001). The decrease in serotonin pathway metabolites was associated with manifestations of portal hypertension (p = 0.026), the development of hepatocellular insufficiency (p = 0.008) (hypoalbuminemia; hypocoagulation), and jaundice (p < 0.001), while changes in the kynurenine pathway metabolite xanthurenic acid were associated with the development of hepatic encephalopathy (p = 0.044). Depending on the etiological factors of cirrhosis, disturbances in the metabolic profile may be involved in various pathogenetic pathways.}, }
@article {pmid39589128, year = {2025}, author = {Agnew, A and Humm, E and Zhou, K and Gunsalus, RP and Zhou, ZH}, title = {Structure and identification of the native PLP synthase complex from Methanosarcina acetivorans lysate.}, journal = {mBio}, volume = {16}, number = {1}, pages = {e0309024}, pmid = {39589128}, issn = {2150-7511}, support = {T32 GM145388/GM/NIGMS NIH HHS/United States ; 1911781//National Science Foundation (NSF)/ ; S10 OD018111/OD/NIH HHS/United States ; R01 GM071940/GM/NIGMS NIH HHS/United States ; T90 DE030860/DE/NIDCR NIH HHS/United States ; R01GM071940, T32GM145388//HHS | NIH | National Institute of General Medical Sciences (NIGMS)/ ; T90DE030860//HHS | NIH | National Institute of Dental and Craniofacial Research (NIDCR)/ ; DE-FC-02-372 02ER63421//U.S. Department of Energy (DOE)/ ; }, mesh = {*Methanosarcina/enzymology/genetics/chemistry ; *Cryoelectron Microscopy ; *Archaeal Proteins/chemistry/metabolism/genetics ; Models, Molecular ; Protein Conformation ; Pyridoxal Phosphate/metabolism ; Proteomics ; }, abstract = {Many protein-protein interactions behave differently in biochemically purified forms as compared to their in vivo states. As such, determining native protein structures may elucidate structural states previously unknown for even well-characterized proteins. Here, we apply the bottom-up structural proteomics method, cryoID, toward a model methanogenic archaeon. While they are keystone organisms in the global carbon cycle and active members of the human microbiome, there is a general lack of characterization of methanogen enzyme structure and function. Through the cryoID approach, we successfully reconstructed and identified the native Methanosarcina acetivorans pyridoxal 5'-phosphate (PLP) synthase (PdxS) complex directly from cryogenic electron microscopy (cryo-EM) images of fractionated cellular lysate. We found that the native PdxS complex exists as a homo-dodecamer of PdxS subunits, and the previously proposed supracomplex containing both the synthase (PdxS) and glutaminase (PdxT) was not observed in cellular lysate. Our structure shows that the native PdxS monomer fashions a single 8α/8β TIM-barrel domain, surrounded by seven additional helices to mediate solvent and interface contacts. A density is present at the active site in the cryo-EM map and is interpreted as ribose 5-phosphate. In addition to being the first reconstruction of the PdxS enzyme from a heterogeneous cellular sample, our results reveal a departure from previously published archaeal PdxS crystal structures, lacking the 37-amino-acid insertion present in these prior cases. This study demonstrates the potential of applying the cryoID workflow to capture native structural states at atomic resolution for archaeal systems, for which traditional biochemical sample preparation is nontrivial.IMPORTANCEArchaea are one of the three domains of life, classified as a phylogenetically distinct lineage. There is a paucity of known enzyme structures from organisms of this domain, and this is often exacerbated by characteristically difficult growth conditions and a lack of readily available molecular biology toolkits to study proteins in archaeal cells. As a result, there is a gap in knowledge concerning the mechanisms governing archaeal protein behavior and their impacts on both the environment and human health; case in point, the synthesis of the widely utilized cofactor pyridoxal 5'-phosphate (PLP; a vitamer of vitamin B6, which humans cannot produce). By leveraging the power of single-particle cryo-EM and map-to-primary sequence identification, we determine the native structure of PLP synthase from cellular lysate. Our workflow allows the (i) rapid examination of new or less characterized systems with minimal sample requirements and (ii) discovery of structural states inaccessible by recombinant expression.}, }
@article {pmid39584055, year = {2024}, author = {Kajova, M and Khawaja, T and Levonen, I and Pietilä, JP and Virtanen, J and Pakkanen, SH and Välimaa, H and Nousiainen, A and Hepojoki, J and Sironen, T and Vierikko, A and Ihalainen, J and Vapalahti, O and Kantele, A}, title = {Convalescent plasma therapy for COVID-19 - Donor selection strategies and establishment of a plasma bank.}, journal = {New microbes and new infections}, volume = {62}, number = {}, pages = {101525}, pmid = {39584055}, issn = {2052-2975}, abstract = {BACKGROUND: Early in the COVID-19 pandemic, convalescent plasma (CP) emerged as a potentially effective treatment neutralising SARS-CoV-2. Early CP therapy with high neutralising antibody (NAb) titre may benefit COVID-19 outpatients and, in sufficient quantities even some hospitalised patients. This study details the process of setting up a CP bank, containing high- and low-titre CP for a clinical trial.<br><br>STUDY DESIGN AND METHODS: We identified 18-65-year-old convalescents with SARS-CoV-2 NAb titres of &#x2265;1:40 in microneutralisation test (MNT). Following eligibility pre-screening, the Finnish Red Cross Blood Service (FRCBS) determined suitability as CP donors.<br><br>RESULTS: Of the 6466 COVID-19 convalescents contacted, 1481 provided serum, with 851 (57.5&#xa0;%) exhibiting NAb titres &#x2265;1:40. Participation barriers included reluctance, advanced age and, for women, insufficient body size. Of the volunteers, 125 were evaluated at FRCBS, with major exclusions for HLA antibodies (42 women), interferon antibodies (five men), and NAb titres waning below 1:20 (16 participants). Finally, 70 underwent plasmapheresis, resulting in 50 suitable CP donors (0.8&#xa0;% of initial contacts and 3.4&#xa0;% of those tested for NAb).<br><br>DISCUSSION: The process of setting up a CP bank proved challenging. Excessive laboratory workloads during a pandemic hamper their ability to conduct MNT, underscoring the need for rapid screening tests. Only a small proportion of our convalescents exhibited high-titre CP, this fraction declining over time because of waning immunity. Strict plasmapheresis criteria further constrained donor eligibility. Establishing a plasma bank requires meticulous planning to maximize efficiency. Detailed insights from current experiences may prove critical in future pandemics before other remedies and vaccines become available.}, }
@article {pmid39582897, year = {2024}, author = {Wang, Z and Wu, X and Wang, Y and Wen, Q and Cui, B and Zhang, F}, title = {Colonic transendoscopic enteral tubing is revolutionizing intestinal therapeutics, diagnosis, and microbiome research.}, journal = {Therapeutic advances in gastroenterology}, volume = {17}, number = {}, pages = {17562848241301574}, pmid = {39582897}, issn = {1756-283X}, abstract = {The intestine, as a crucial organ of the human body, has remained enigmatic despite the remarkable advancements in modern medical technology. Over the past decades, the invention of endoscopic technology has made the noninvasive intervention of the intestine a reality, expanding diagnostic and therapeutic options for diseases. However, due to the single-treatment feature of endoscopic procedures, continuous or repeated medication administration, sampling, and decompression drainage within the intestine have yet to be fulfilled. These limitations persisted until the invention of colonic transendoscopic enteral tubing (TET) in 2014, which realized repeated fecal microbiota transplantation, medication administration, and decompression drainage for the treatment of colon perforation and intestinal obstruction, as well as in situ dynamic sampling. These breakthroughs have not gone unnoticed, gaining global attention and recommendations from guidelines and consensuses. TET has emerged as a novel microbial research tool that offers new paradigms for human microbiome research. This review aims to update the research progress based on TET.}, }
@article {pmid39581825, year = {2024}, author = {Isali, I and Almassi, N and Nizam, A and Campbell, R and Weight, C and Gupta, S and Pooja, G and Fulmes, A and Mishra, K and Abbosh, P and Bukavina, L}, title = {State of the Art: The Microbiome in Bladder Cancer.}, journal = {Urologic oncology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.urolonc.2024.11.008}, pmid = {39581825}, issn = {1873-2496}, abstract = {This review assesses the current understanding of the relationship between the human microbiome and BCa. Recognizing how the microbiome affects the tumor microenvironment provides valuable insights into cancer biology, potentially uncovering interactions that could be leveraged to develop innovative therapeutic approaches. By clarifying these intricate microbial-tumor dynamics, novel targets for microbiome-based interventions can be identified, ultimately improving treatment effectiveness and patient outcomes. Current literature lacks comprehensive insights into the effects of BCa treatment on the microbiome and the prevalence of immunotherapy-related toxicities. Further research into the microbiome's role in BCa development could bridge the gap between fundamental research and therapeutic applications. Implementing microbiome surveillance, metagenomic sequencing, and metabolomics in clinical trials could deepen our understanding of BCa and its treatment. This review explores the existing understanding of the urine, tissue, and gut microbiomes and their connections to BCa. Enhanced knowledge of these relationships can pave the way for future research to identify reliable disease predictors, prognostic markers, and novel therapeutic targets.}, }
@article {pmid39575247, year = {2024}, author = {Zhu, Y and Liang, X and Zhi, M and Li, L and Zhang, G and Chen, C and Wang, L and Wang, P and Zhong, N and Feng, Q and Li, Z}, title = {Succession of the multi-site microbiome along pancreatic ductal adenocarcinoma tumorigenesis.}, journal = {Frontiers in immunology}, volume = {15}, number = {}, pages = {1487242}, pmid = {39575247}, issn = {1664-3224}, mesh = {Humans ; *Carcinoma, Pancreatic Ductal/microbiology/pathology ; *Pancreatic Neoplasms/microbiology/pathology ; Male ; Female ; Microbiota ; Middle Aged ; Saliva/microbiology ; Aged ; Carcinogenesis ; Bacteria/classification/genetics ; Pancreatitis, Chronic/microbiology ; RNA, Ribosomal, 16S/genetics ; Adult ; }, abstract = {BACKGROUND: To investigate microbial characteristics across multibody sites from chronic pancreatitis (CP), through pancreatic benign tumors, to pancreatic ductal adenocarcinoma (PDAC) at different stages.<br><br>METHODS: 16S ribosomal RNA (rRNA) amplicon sequencing was conducted on saliva, duodenal fluid, and pancreatic tissue obtained via endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) of patients with CP, pancreatic benign tumors, PDAC in stage I/II, III, and IV. The neutral community model (NCM) assessed the microbial assembly contribution and MaAslin2 identified the differential microbes.<br><br>RESULTS: From CP to stage IV PDAC patients, there was a marked surge in influence of salivary and duodenal microbiota on constitution of pancreatic microbial communities. Our observations revealed a successive alteration in microbial species across various bodily sites during PDAC tumorigenesis. Notably, Porphyromonas gingivalis, Treponema denticola, Peptoanaerobacter stomatis, Propionibacterium acidifaciens, Porphyromonas endodontalis, Filifactor alocis, etc., sequentially increased along PDAC progression in pancreatic tissue, whereas bacteria commonly used as probiotics Bifidobacterium breve, Lactiplantibacillus plantarum, etc., declined. Furthermore, the sequentially escalating trends of Peptoanaerobacter stomatis and Propionibacterium acidifaciens during PDAC tumorigenesis were mirrored in duodenal fluid and saliva. Porphyromonas gingivalis, Porphyromonas endodontalis, and Filifactor alocis, which intensified from CP to stage IV PDAC in pancreatic tissue, were also found to be enriched in saliva of patients with short-term survival (STS) compared with those with long-term survival (LTS).<br><br>CONCLUSIONS: Salivary and duodenal microorganisms were prominent factors in shaping pancreatic microbial landscape in PDAC context. Further exploration of these microbial entities is imperative to unravel their specific roles in PDAC pathogenesis, potentially yielding insights for future therapeutic strategies.}, }
@article {pmid39575165, year = {2024}, author = {Teng, Z and Li, Q and Shen, XF}, title = {Correlations of Nasal Microbiome with Allergic Rhinitis and Its Symptoms Severity in Children Progression.}, journal = {Journal of asthma and allergy}, volume = {17}, number = {}, pages = {1187-1196}, pmid = {39575165}, issn = {1178-6965}, abstract = {OBJECTIVE: Human microbiome is involved in the pathogenesis of allergic diseases, but the impact of nasal microbiota on allergic rhinitis (AR) symptoms severity has not been evaluated. This study aimed to characterize nasal microbiome in AR children and its correlations with AR symptoms.<br><br>METHODS: According to diagnostic guidelines for AR, 45 AR children and 40&#xa0;healthy subjects were recruited from July to August in 2023. Based on the total score of nasal symptoms (TNSS), the 45 AR patients were divided into a mild AR group (MAR) (n = 16) and a moderate or severe AR group (MSAR) (n = 29). Nasal swabs were collected for microbiome analysis using 16S-rDNA sequencing.<br><br>RESULTS: The Simpson and Shannon indices were significantly higher in the AR group compared to the health control group, indicating an increase of nasal microbiota at the species evenness level in AR children. Moreover, the species evenness was significantly increased in the MSAR group compared to the MAR group. Staphylococcus (member of the Firmicutes phylum) was significantly dominant in the AR group, but Moraxella (member of the Proteobacteria phylum) was significantly dominant in the CG group. The LEfSe analysis showed that the mean relative abundances of Ralstonia in the MSAR group was higher than that in the MAR group. Meanwhile, the abundance divided by Ralstonia of Spearman correlation coefficients was positively correlated with the TNSS of AR symptoms (r = 0.4, P = 0.009).<br><br>CONCLUSION: The elevation of species evenness in nasal microbiome was likely related to the aggravation of AR symptoms. The Ralstonia may play a pro-inflammatory role in AR.}, }
@article {pmid39574598, year = {2024}, author = {Nguyen, UT and Salamzade, R and Sandstrom, S and Swaney, MH and Townsend, L and Wu, SY and Cheong, JZA and Sardina, JA and Ludwikoski, I and Rybolt, M and Wan, H and Carlson, C and Zarnowski, R and Andes, D and Currie, C and Kalan, L}, title = {Large-scale investigation for antimicrobial activity reveals novel defensive species across the healthy skin microbiome.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {39574598}, issn = {2692-8205}, support = {R35 GM137828/GM/NIGMS NIH HHS/United States ; T32 GM135066/GM/NIGMS NIH HHS/United States ; U19 AI142720/AI/NIAID NIH HHS/United States ; }, abstract = {The human skin microbiome constitutes a dynamic barrier that can impede pathogen invasion by producing antimicrobial natural products. Gene clusters encoding for production of secondary metabolites, biosynthetic gene clusters (BGCs), that are enriched in the human skin microbiome relative to other ecological settings, position this niche as a promising source for new natural product mining. Here, we introduce a new human microbiome isolate collection, the EPithelial Isolate Collection (EPIC). It includes a large phylogenetically diverse set of human skin-derived bacterial strains from eight body sites. This skin collection, consisting of 980 strains is larger and more diverse than existing resources, includes hundreds of rare and low-abundance strains, and hundreds of unique BGCs. Using a large-scale co-culture screen to assess 8,756 pairwise interactions between skin-associated bacteria and potential pathogens, we reveal broad antifungal activity by skin microbiome members. Integrating 287 whole isolate genomes and 268 metagenomes from sampling sites demonstrates that while the distribution of BGC types is stable across body sites, specific gene cluster families (GCFs), each predicted to encode for a distinct secondary metabolite, can substantially vary. Sites that are dry or rarely moist harbor the greatest potential for discovery of novel bioactive metabolites. Among our discoveries are four novel bacterial species, three of which exert significant and broad-spectrum antifungal activity. This comprehensive isolate collection advances our understanding of the skin microbiomes biosynthetic capabilities and pathogen-fighting mechanisms, opening new avenues towards antimicrobial drug discovery and microbiome engineering.}, }
@article {pmid39571733, year = {2024}, author = {Yu, J and Feng, L and Luo, Z and Yang, J and Zhang, Q and Liu, C and Liang, D and Xie, Y and Li, H and Gong, J and He, Z and Lan, P}, title = {Interleukin-10 deficiency suppresses colorectal cancer metastasis by enriching gut Parabacteroides distasonis.}, journal = {Journal of advanced research}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jare.2024.11.024}, pmid = {39571733}, issn = {2090-1224}, abstract = {INTRODUCTION: The intricate interplay of interleukin-10 (IL-10) and gut microbiota influences tumor development and progression, yet the impacts on colorectal cancer (CRC) metastasis remain incompletely understood.<br><br>METHODS: The impact of Il10 deficiency on CRC metastasis was first evaluated in CRC metastasis tumor samples and mouse model. Antibiotic sterilization and fecal microbiota transplantation (FMT) experiment were used to assess the role of gut microbiota in IL-10 mediated CRC metastasis, and full-length 16S rDNA sequencing analysis further identified the potential target bacteria influencing CRC metastasis. The inhibitory effect of Parabacteroides distasonis (P. distasonis) on CRC metastasis was evaluated by oral administration in mice. Key metabolites involved in P. distasonis inhibition of CRC metastasis was identified by widely-targeted metabolome analysis and validated both in vivo and in vitro. The underlying mechanisms of P-hydroxyphenyl acetic acid (4-HPAA) inhibiting CRC metastasis was investigated via RNA-sequencing and validated in cellular experiments.<br><br>RESULTS: We revealed that serum IL-10 levels were markedly elevated in metastatic CRC patients compared to non-metastatic cases. In parallel, Il10-deficiency (Il10[-/-]) in mice resulted in decreased CRC metastasis in a gut microbiota-dependent manner. Mechanistically, Il10[-/-] mice reshaped gut microbiota composition, notably enriching P. distasonis. The enriched P. distasonis produced 4-HPAA, which activated the aryl hydrocarbon receptor (AHR) and subsequently inhibited the expression of VEGFA, a typical oncogene, thereby sequentially suppressing CRC metastasis. Importantly, engineered bacteria capable of producing 4-HPAA effectively hindered CRC metastasis. Furthermore, AHR depletion significantly disrupted the 4-HPAA-induced reduction in CRC cell migration and the inhibition of metastasis in both in vitro and in vivo lung metastasis mouse models.<br><br>CONCLUSIONS: These findings demonstrate the significance of IL-10 deficiency in suppressing CRC metastasis through the 4-HPPA-AHR-VEGFA axis mediated by gut P. distasonis, suggesting that P. distasonis or 4-HPAA supplementation could offer a promising therapeutic strategy for CRC metastasis prevention.}, }
@article {pmid39569373, year = {2024}, author = {Talukdar, D and Sarkar, M and Ahrodia, T and Kumar, S and De, D and Nath, S and Jana, P and Verma, J and Mehta, O and Kothidar, A and Yodhaanjali, JR and Sharma, K and Bakshi, S and Singh, U and Kshetrapal, P and Wadhwa, N and Thiruvengadam, R and ,  and Nair, GB and Bhatnagar, S and Mukherjee, S and Das, B}, title = {Previse preterm birth in early pregnancy through vaginal microbiome signatures using metagenomics and dipstick assays.}, journal = {iScience}, volume = {27}, number = {11}, pages = {111238}, pmid = {39569373}, issn = {2589-0042}, abstract = {Annually, in India, 13% of all newborns are preterm, accounting for 23.4% of preterm birth (PTB) globally. The composition and diversity of the vaginal microbiome have a notable degree of ethnic inequality. For understanding differences in vaginal microbiome composition and functions between adverse and normal pregnancy, we have collected, processed and sequenced 600 high vaginal swab (HVS) samples across the three trimesters of pregnancy from 140 women who delivered at term and 60 women who delivered PTB, adopting a targeted metagenomics approach. The microbial signatures in HVS samples showed Lactobacillus genera to be highly abundant in term birth (TB), while in early pregnancy the abundances of Gardnerella, Atopobium, and Sneathia were found to be high in PTB. We further extended our analysis, identified specific microbial genomic signatures, and developed a dipstick assay for rapid identification of PTB-associated microbiota in HVS samples in low-resource settings.}, }
@article {pmid39565565, year = {2024}, author = {Pino, A and Hiippala, K and Ronkainen, A and Vaccalluzzo, A and Caggia, C and Satokari, R and Randazzo, CL}, title = {Adhesion Properties and Pathogen Inhibition of Vaginal-Derived Lactobacilli.}, journal = {Probiotics and antimicrobial proteins}, volume = {}, number = {}, pages = {}, pmid = {39565565}, issn = {1867-1314}, abstract = {In the present study, twenty-seven (27) lactobacilli strains, isolated from the vagina of healthy Italian women of reproductive age, were screened for probiotic properties. The strains were evaluated for antagonistic activity against pathogens, adhesion abilities, and potential to displace and/or inhibit the adhesion of previously adhered pathogens as a primary strain selection criterion. Overall, all the tested lactobacilli inhibited at least three pathogens, and the majority of them exhibited antimicrobial activity against Enterobacter cloacae DSM 30054, Pseudomonas aeruginosa DSM 3227, and Pseudomonas aeruginosa DSM 1117. The complete neutralization of antimicrobial activity after cell-free supernatant (CFS) neutralization suggested a pivotal role for lactic acid or other organic acids secreted by the lactobacilli. The strains showed variability in their adhesion levels, but all tested strains adhered to both human colonic epithelial cells (HT-29) and vaginal cells (VK2/E6E7) with adhesion percentages exceeding 1%. The ability to displace or inhibit pathogens was dependent on the pathogen and the lactobacilli strain; the pathogen displacement levels ranged from 9 to 82%, while pathogen exclusion levels varied from 1 to 99%. In conclusion, this study demonstrates the protective effect of vaginal lactobacilli against pathogens and confirms the suitability of the vaginal microbiota as a source of potential probiotic strains. The selected lactobacilli hold promise for the formulation of supplements to enhance genitourinary tract health.}, }
@article {pmid39565308, year = {2024}, author = {Dong, PT and Shi, W and He, X and Borisy, GG}, title = {Adhesive interactions within microbial consortia can be differentiated at the single-cell level through expansion microscopy.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {121}, number = {48}, pages = {e2411617121}, pmid = {39565308}, issn = {1091-6490}, support = {R01 DE023810/DE/NIDCR NIH HHS/United States ; DE023810//HHS | NIH (NIH)/ ; DE022586//HHS | NIH (NIH)/ ; DE030943//HHS | NIH (NIH)/ ; R01 DE022586/DE/NIDCR NIH HHS/United States ; K99 DE033794/DE/NIDCR NIH HHS/United States ; K99DE033794//HHS | NIH (NIH)/ ; R01 DE030943/DE/NIDCR NIH HHS/United States ; }, mesh = {*Biofilms/growth &amp; development ; *Microbial Consortia/physiology ; *Bacterial Adhesion/physiology ; Single-Cell Analysis/methods ; Microscopy/methods ; Streptococcus/physiology ; Streptococcus mutans/physiology ; Fusobacterium nucleatum/physiology ; }, abstract = {Investigating microbe-microbe interactions at the single-cell level is critical to unraveling the ecology and dynamics of microbial communities. In many situations, microbes assemble themselves into densely packed multispecies biofilms. The density and complexity pose acute difficulties for visualizing individual cells and analyzing their interactions. Here, we address this problem through an unconventional application of expansion microscopy, which allows for the "decrowding" of individual bacterial cells within a multispecies community. Expansion microscopy generally has been carried out under isotropic expansion conditions and used as a resolution-enhancing method. In our variation of expansion microscopy, we carry out expansion under heterotropic conditions; that is, we expand the space between bacterial cells but not the space within individual cells. The separation of individual bacterial cells from each other reflects the competition between the expansion force pulling them apart and the adhesion force holding them together. We employed heterotropic expansion microscopy to study the relative strength of adhesion in model biofilm communities. These included mono- and dual-species Streptococcus biofilms and a three-species synthetic community (Fusobacterium nucleatum, Streptococcus mutans, and Streptococcus sanguinis) under conditions that facilitated interspecies coaggregation. Using adhesion mutants, we investigated the interplay between F. nucleatum outer membrane protein RadD and different Streptococcus species. We also examined the Schaalia-TM7 epibiont association. Quantitative proximity analysis was used to evaluate the separation of individual microbial members. Our study demonstrates that heterotropic expansion microscopy can "decrowd" dense biofilm communities, improve visualization of individual bacterial members, and enable analysis of microbe-microbe adhesive interactions at the single-cell level.}, }
@article {pmid39563467, year = {2024}, author = {Liu, R and Wang, Y and Cheng, D}, title = {Micro-DeMix: a mixture beta-multinomial model for investigating the heterogeneity of the stool microbiome compositions.}, journal = {Bioinformatics (Oxford, England)}, volume = {40}, number = {12}, pages = {}, pmid = {39563467}, issn = {1367-4811}, support = {DMS-2220523//National Institute of Health/ ; 854127//Simons Foundation Collaboration/ ; }, mesh = {Humans ; *Feces/microbiology ; *Gastrointestinal Microbiome ; *Software ; Inflammatory Bowel Diseases/microbiology ; }, abstract = {MOTIVATION: Extensive research has uncovered the critical role of the human gut microbiome in various aspects of health, including metabolism, nutrition, physiology, and immune function. Fecal microbiota is often used as a proxy for understanding the gut microbiome, but it represents an aggregate view, overlooking spatial variations across different gastrointestinal (GI) locations. Emerging studies with spatial microbiome data collected from specific GI regions offer a unique opportunity to better understand the spatial composition of the stool microbiome.<br><br>RESULTS: We introduce Micro-DeMix, a mixture beta-multinomial model that deconvolutes the fecal microbiome at the compositional level by integrating stool samples with spatial microbiome data. Micro-DeMix facilitates the comparison of microbial compositions across different GI regions within the stool microbiome through a hypothesis-testing framework. We demonstrate the effectiveness and efficiency of Micro-DeMix using multiple simulated datasets and the inflammatory bowel disease data from the NIH Integrative Human Microbiome Project.<br><br>The R package is available at https://github.com/liuruoqian/MicroDemix.}, }
@article {pmid39562050, year = {2024}, author = {Li, N and Li, Y and Huang, Z and Cao, Z and Cao, C and Gao, X and Zuo, T}, title = {Faecal phageome transplantation alleviates intermittent intestinal inflammation in IBD and the timing of transplantation matters: a preclinical proof-of-concept study in mice.}, journal = {Gut}, volume = {}, number = {}, pages = {}, doi = {10.1136/gutjnl-2024-333598}, pmid = {39562050}, issn = {1468-3288}, }
@article {pmid39561848, year = {2024}, author = {Yang, J and Sun, S and Sun, N and Lu, L and Zhang, C and Shi, W and Zhao, Y and Jia, S}, title = {HMMER-Extractor: an auxiliary toolkit for identifying genomic macromolecular metabolites based on Hidden Markov Models.}, journal = {International journal of biological macromolecules}, volume = {283}, number = {Pt 2}, pages = {137666}, doi = {10.1016/j.ijbiomac.2024.137666}, pmid = {39561848}, issn = {1879-0003}, mesh = {*Markov Chains ; *Software ; Humans ; Genome, Bacterial ; Genomics/methods ; Macromolecular Substances/chemistry ; Computational Biology/methods ; Microbiota/genetics ; }, abstract = {Human microbiome contains various microbial macromolecules with important biological functions. The Hidden Markov Models (HMMs) can overcome the problem of low similarity sequences with distant relationships and are widely implemented within various sequence alignment softwares. However, the HMM-based sequence alignments can generate a large number of results, how to quickly screen and batch extract target homologs from microbiomes is the major sticking points. It is necessary to develop an integrated gene filter and extraction pipeline to quickly and accurately screen homologs. Here, we introduced the HMMER-Extractor for amino acids or nucleotide sequences extraction, which was a supporting toolkit through provided filtering scores and an iterative keyword matching (IKM) logic. To make it more user-friendly and accessible, we further presented a visualized web server platform. An interactive HTML output provided a user-friendly way to browse homologous annotations and sequence extraction. The web server provided the community with a streamlined and user-friendly interface to analyze microbiomes. Through the HMMER-Extractor, we constructed a cardiovascular disease related gene dataset of the macromolecular metabolite trimethylamine (TMA) and lipopolysaccharide (LPS) based on 46,699 bacterial genomes from human gut. Approximately 21,014 and 1961 bacterial strains were identified to contain the cnt or cut operon of TMA, and the waa gene cluster of LPS, respectively. The Escherichia coli occupied the largest proportion among all the bacterial species, which belonged to the phyla Firmicutes. The HMMER-Extractor toolkit is an integrated pipeline and has been proven to be accurate and fast in extracting target macromolecular encoding genes from microbial genomes.}, }
@article {pmid39556491, year = {2025}, author = {Shete, O and Ghosh, TS}, title = {Normal Gut Microbiomes in Diverse Populations: Clinical Implications.}, journal = {Annual review of medicine}, volume = {76}, number = {1}, pages = {95-114}, doi = {10.1146/annurev-med-051223-031809}, pmid = {39556491}, issn = {1545-326X}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; }, abstract = {The human microbiome is a sensor and modulator of physiology and homeostasis. Remarkable tractability underpins the promise of therapeutic manipulation of the microbiome. However, the definition of a normal or healthy microbiome has been elusive. This is in part due to the underrepresentation of minority groups and major global regions in microbiome studies to date. We review studies of the microbiome in different populations and highlight a commonality among health-associated microbiome signatures along with major drivers of variation. We also provide an overview of microbiome-associated therapeutic interventions for some widespread, widely studied diseases. We discuss sources of bias and the challenges associated with defining population-specific microbiome reference bases. We propose a roadmap for defining normal microbiome references that can be used for population-customized microbiome therapeutics and diagnostics.}, }
@article {pmid39555415, year = {2024}, author = {Chen, XY and Liu, Y and Zhu, WB and Li, SH and Wei, S and Cai, J and Lin, Y and Liang, JK and Yan, GM and Guo, L and Hu, C}, title = {Arming oncolytic M1 virus with gasdermin E enhances antitumor efficacy in breast cancer.}, journal = {iScience}, volume = {27}, number = {11}, pages = {111148}, pmid = {39555415}, issn = {2589-0042}, abstract = {Pyroptosis, driven by the N-terminal domain of gasdermin proteins (GSDM), promotes antitumor immunity by attracting lymphocytes to the tumor microenvironment (TME). However, current pyroptosis-inducing therapies like drug injections and phototherapy are limited to localized treatments, making them unsuitable for widespread or microscopic metastatic lesions. This study engineered oncolytic M1 viruses (rM1-mGSDME_FL and rM1-mGSDME_NT) to selectively deliver GSDME to tumor cells. These modified viruses enhanced tumor cell death in breast cancer models, suppressed tumor growth, extended survival in mice, and boosted immune cell infiltration, demonstrating significant anticancer potential through pyroptosis induction.}, }
@article {pmid39547283, year = {2024}, author = {Zelasko, S and Swaney, MH and Sandstrom, S and Lee, KE and Dixon, J and Riley, C and Watson, L and Godfrey, JJ and Ledrowski, N and Rey, F and Safdar, N and Seroogy, CM and Gern, JE and Kalan, L and Currie, C}, title = {Early-life upper airway microbiota are associated with decreased lower respiratory tract infections.}, journal = {The Journal of allergy and clinical immunology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jaci.2024.11.008}, pmid = {39547283}, issn = {1097-6825}, abstract = {BACKGROUND: Microbial interactions mediating colonization resistance play key roles within the human microbiome, shaping susceptibility to infection from birth. The role of the nasal and oral microbiome in the context of early life respiratory infections and subsequent allergic disease risk remains understudied.<br><br>OBJECTIVES: Our aim was to gain insight into microbiome-mediated defenses and respiratory pathogen colonization dynamics within the upper respiratory tract during infancy.<br><br>METHODS: We performed shotgun metagenomic sequencing of nasal (n&#xa0;= 229) and oral (n&#xa0;= 210) microbiomes from our Wisconsin Infant Study Cohort at age 24 months and examined the influence of participant demographics and exposure history on microbiome composition. Detection of viral and bacterial respiratory pathogens by RT-PCR and culture-based studies with antibiotic susceptibility testing, respectively, to assess pathogen carriage was performed. Functional bioassays were used to evaluate pathogen inhibition by respiratory tract commensals.<br><br>RESULTS: Participants with early-life lower respiratory tract infection were more likely to be formula fed, attend day care, and experience wheezing. Composition of the nasal, but not oral, microbiome associated with prior lower respiratory tract infection, namely lower alpha diversity, depletion of Prevotella, and enrichment of Moraxella catarrhalis including drug-resistant strains. Prevotella originating from healthy microbiomes had higher biosynthetic gene cluster abundance and exhibited contact-independent inhibition of M catarrhalis.<br><br>CONCLUSIONS: These results suggest interbacterial competition affects nasal pathogen colonization. This work advances understanding of protective host-microbe interactions occurring in airway microbiomes that alter infection susceptibility in early life.}, }
@article {pmid39545965, year = {2024}, author = {Pawlik, MT and Rinneberg, G and Koch, A and Meyringer, H and Loew, TH and Kjellberg, A}, title = {Is there a rationale for hyperbaric oxygen therapy in the patients with Post COVID syndrome? : A critical review.}, journal = {European archives of psychiatry and clinical neuroscience}, volume = {274}, number = {8}, pages = {1797-1817}, pmid = {39545965}, issn = {1433-8491}, mesh = {Humans ; *Hyperbaric Oxygenation/methods ; *COVID-19/therapy/complications ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; }, abstract = {The SARS-CoV-2 pandemic has resulted in 762 million infections worldwide from 2020 to date, of which approximately ten percent are suffering from the effects after infection in 2019 (COVID-19) [1, 40]. In Germany, it is now assumed that at least one million people suffer from post-COVID condition with long-term consequences. These have been previously reported in diseases like Myalgic Encephalomyelitis (ME) and Chronic Fatigue Syndrome (CFS). Symptoms show a changing variability and recent surveys in the COVID context indicate that 10-30 % of outpatients, 50 to 70% of hospitalised patients suffer from sequelae. Recent data suggest that only 13% of all ill people were completely free of symptoms after recovery [3, 9]. Current hypotheses consider chronic inflammation, mitochondrial dysfunction, latent viral persistence, autoimmunity, changes of the human microbiome or multilocular sequelae in various organ system after infection. Hyperbaric oxygen therapy (HBOT) is applied since 1957 for heart surgery, scuba dive accidents, CO intoxication, air embolisms and infections with anaerobic pathogens. Under hyperbaric pressure, oxygen is physically dissolved in the blood in higher concentrations and reaches levels four times higher than under normobaric oxygen application. Moreover, the alternation of hyperoxia and normoxia induces a variety of processes at the cellular level, which improves oxygen supply in areas of locoregional hypoxia. Numerous target gene effects on new vessel formation, anti-inflammatory and anti-oedematous effects have been demonstrated [74]. The provision of intermittently high, local oxygen concentrations increases repair and regeneration processes and normalises the predominance of hyperinflammation. At present time only one prospective, randomized and placebo-controlled study exists with positive effects on global cognitive function, attention and executive function, psychiatric symptoms and pain interference. In conclusion, up to this date HBO is the only scientifically proven treatment in a prospective randomized controlled trial to be effective for cognitive improvement, regeneration of brain network and improvement of cardiac function. HBOT may have not only theoretical but also potential impact on targets of current pathophysiology of Post COVID condition, which warrants further scientific studies in patients.}, }
@article {pmid39545326, year = {2025}, author = {Shah, AB and Shim, SH}, title = {Human microbiota peptides: important roles in human health.}, journal = {Natural product reports}, volume = {42}, number = {1}, pages = {151-194}, doi = {10.1039/d4np00042k}, pmid = {39545326}, issn = {1460-4752}, mesh = {Humans ; *Microbiota/physiology ; *Peptides/metabolism/chemistry ; Anti-Bacterial Agents/pharmacology/chemistry ; Bacteria/metabolism ; Biological Products/pharmacology/chemistry/metabolism ; }, abstract = {Covering: 1974 to 2024Human microbiota consist of a diverse array of microorganisms, such as bacteria, Eukarya, archaea, and viruses, which populate various parts of the human body and live in a cooperatively beneficial relationship with the host. They play a crucial role in supporting the functional balance of the microbiome. The coevolutionary progression has led to the development of specialized metabolites that have the potential to substitute traditional antibiotics in combating global health challenges. Although there has been a lot of research on the human microbiota, there is a considerable lack of understanding regarding the wide range of peptides that these microbial populations produce. Particularly noteworthy are the antibiotics that are uniquely produced by the human microbiome, especially by bacteria, to protect against invasive infections. This review seeks to fill this knowledge gap by providing a thorough understanding of various peptides, along with their in-depth biological importance in terms of human disorders. Advancements in genomics and the understanding of molecular mechanisms that control the interactions between microbiota and hosts have made it easier to find peptides that come from the human microbiome. We hope that this review will serve as a basis for developing new therapeutic approaches and personalized healthcare strategies. Additionally, it emphasizes the significance of these microbiota in the field of natural product discovery and development.}, }
@article {pmid39543873, year = {2024}, author = {Saraswat, I and Goel, A}, title = {Therapeutic Modulation of the Microbiome in Oncology: Current Trends and Future Directions.}, journal = {Current pharmaceutical biotechnology}, volume = {}, number = {}, pages = {}, doi = {10.2174/0113892010353600241109132441}, pmid = {39543873}, issn = {1873-4316}, abstract = {Cancer is a predominant cause of mortality worldwide, necessitating the development of innovative therapeutic techniques. The human microbiome, particularly the gut microbiota, has become a significant element in cancer research owing to its essential role in sustaining health and influencing disease progression. This review examines the microbiome's makeup and essential functions, including immunological modulation and metabolic regulation, which may be evaluated using sophisticated methodologies such as metagenomics and 16S rRNA sequencing. The microbiome influences cancer development by promoting inflammation, modulating the immune system, and producing carcinogenic compounds. Dysbiosis, or microbial imbalance, can undermine the epithelial barrier and facilitate cancer. The microbiome influences chemotherapy and radiation results by modifying drug metabolism, either enhancing or reducing therapeutic efficacy and contributing to side effects and toxicity. Comprehending these intricate relationships emphasises the microbiome's significance in oncology and accentuates the possibility for microbiome-targeted therapeutics. Contemporary therapeutic approaches encompass the utilisation of probiotics and dietary components to regulate the microbiome, enhance treatment efficacy, and minimise unwanted effects. Advancements in research indicate that personalised microbiome-based interventions, have the potential to transform cancer therapy, by providing more effective and customised treatment alternatives. This study aims to provide a comprehensive analysis of the microbiome's influence on the onset and treatment of cancer, while emphasising current trends and future possibilities for therapeutic intervention.}, }
@article {pmid39541945, year = {2024}, author = {Wu, J and Zeng, W and Xie, H and Cao, M and Yang, J and Xie, Y and Luo, Z and Zhang, Z and Xu, H and Huang, W and Zhou, T and Tan, J and Wu, X and Yang, Z and Zhu, S and Mao, R and He, Z and Lan, P}, title = {Microbiota-induced alteration of kynurenine metabolism in macrophages drives formation of creeping fat in Crohn's disease.}, journal = {Cell host &amp; microbe}, volume = {32}, number = {11}, pages = {1927-1943.e9}, doi = {10.1016/j.chom.2024.10.008}, pmid = {39541945}, issn = {1934-6069}, mesh = {Animals ; Mice ; *Macrophages/microbiology/metabolism ; *Kynurenine/metabolism ; *Crohn Disease/microbiology/metabolism ; *Indoleamine-Pyrrole 2,3,-Dioxygenase/metabolism ; *Adipogenesis ; *Mice, Knockout ; *Disease Models, Animal ; Mice, Inbred C57BL ; Gastrointestinal Microbiome/physiology ; Receptors, Aryl Hydrocarbon/metabolism ; Humans ; Adipocytes/metabolism ; Male ; Mesentery ; Microbiota ; }, abstract = {Hyperplasia of mesenteric tissues in Crohn's disease, called creeping fat (CrF), is associated with surgical recurrence. Although microbiota translocation and colonization have been found in CrF, convincing mouse phenotypes and the underlying mechanisms of CrF formation remain unclear. Utilizing single-nucleus RNA (snRNA) sequencing of CrF and different mouse models, we demonstrate that the commensal Achromobacter pulmonis induces mesenteric adipogenesis through macrophage alteration. Targeted metabolome analysis reveals that L-kynurenine is the most enriched metabolite in CrF. Upregulation of indoleamine 2,3-dioxygenase 1 (IDO1) enhances kynurenine metabolism and drives mesenteric adipogenesis. Leveraging single-cell RNA (scRNA) sequencing of mouse mesenteric tissues and macrophage-specific IDO1 knockout mice, we verify the role of macrophage-sourced L-kynurenine in mesenteric adipogenesis. Mechanistically, L-kynurenine-induced adipogenesis is mediated by the aryl hydrocarbon receptors in adipocytes. Administration of an IDO1 inhibitor or bacteria engineered to degrade L-kynurenine alleviates mesenteric adipogenesis in mice. Collectively, our study demonstrates that microbiota-induced modulation of macrophage metabolism potentiates CrF formation.}, }
@article {pmid39541940, year = {2024}, author = {Monzel, E and Desai, MS}, title = {Bacterial small RNA makes a big impact for gut colonization.}, journal = {Cell host &amp; microbe}, volume = {32}, number = {11}, pages = {1875-1877}, doi = {10.1016/j.chom.2024.10.010}, pmid = {39541940}, issn = {1934-6069}, mesh = {Humans ; *RNA, Bacterial/genetics/metabolism ; *Gastrointestinal Microbiome/genetics ; RNA, Small Untranslated/genetics/metabolism ; Gastrointestinal Tract/microbiology ; Animals ; Dietary Carbohydrates/metabolism ; Gene Expression Regulation, Bacterial ; }, abstract = {The functions of non-coding small RNAs (sRNAs) within the human microbiome remain largely unexplored. In this Cell Host &amp; Microbe issue, El Mouali et al. identify Segatella RNA colonization factor (SrcF), a sRNA from a prevalent gut bacterium Segatella copri. SrcF promotes colonization of S. copri by regulating bacterial degradation of complex dietary carbohydrates.}, }
@article {pmid39540274, year = {2024}, author = {Arcimowicz, M}, title = {Rational treatment of acute rhinosinusitis in the context of increasing antibiotic resistance.}, journal = {Otolaryngologia polska = The Polish otolaryngology}, volume = {78}, number = {6}, pages = {1-11}, doi = {10.5604/01.3001.0054.7506}, pmid = {39540274}, issn = {2300-8423}, mesh = {Humans ; *Sinusitis/drug therapy/microbiology ; *Rhinitis/drug therapy/microbiology ; *Anti-Bacterial Agents/therapeutic use ; Acute Disease ; Drug Resistance, Microbial ; Adult ; COVID-19 ; Drug Resistance, Bacterial ; Rhinosinusitis ; }, abstract = {Acute rhinosinusitis is one of the most common diseases in the population, both in primary and specialist otolaryngological care. It is also responsible for a disturbingly high percentage of prescribed antibiotic therapy, regardless of the etiology of the disease. Despite the fact that acute viral and acute postviral rhinosinusitis dominate among the phenotypes of acute rhinosinusitis, and the development of acute bacterial rhinosinusitis occurs in only 0.5-2% of all cases in adults and 5-10% in children, antibiotics still remain an important element of treatment, despite alarming data on the growing antibiotic resistance and the adverse effect of antibiotics on the human microbiome, leading to dysbiosis. The discovery of antibiotics was one of the greatest achievements of modern medicine, but their inappropriate use leads to the gradual increase in the phenomenon of antibiotic resistance, considered one of the most serious public health problems, recognized by the WHO as one of the 10 greatest threats to human health in the 21[st] century. The unjustified use of antibiotics in outpatient care is the key to the growth of this problem, in parallel with the lack of patient compliance. The COVID pandemic has intensified this unfavourable trend. That is why the knowledge of antibiotic stewardship is so important. According to the guidelines, in the therapy of acute rhinosinusitis, symptomatic and anti-inflammatory treatment dominates, and antibiotic therapy has very strictly defined and limited indications. The latest guidelines also recommend herbal medicines, including BNO 1016, in the treatment of acute viral and postviral rhinosinusitis. Available studies indicate that it has a beneficial effect not only on shortening the duration of the disease and reducing symptoms, but also reduces the need for antibiotic treatment in acute rhinosinusitis. Complications of acute rhinosinusitis are relatively rare and are not related to taking antibiotics.}, }
@article {pmid39539377, year = {2024}, author = {Efremova, I and Alieva, A and Maslennikov, R and Poluektova, E and Zharkova, M and Kudryavtseva, A and Krasnov, G and Zharikov, Y and Nerestyuk, Y and Karchevskaya, A and Ivashkin, V}, title = {Akkermansia muciniphila is associated with normal muscle mass and Eggerthella is related with sarcopenia in cirrhosis.}, journal = {Frontiers in nutrition}, volume = {11}, number = {}, pages = {1438897}, pmid = {39539377}, issn = {2296-861X}, abstract = {BACKGROUND: Sarcopenia and gut dysbiosis are common in cirrhosis. The aim is to study the correlations between the gut microbiota taxa and muscle mass level in cirrhosis.<br><br>METHODS: The study included 40 cirrhosis patients including 18 patients with sarcopenia. The gut microbiota composition was assessed using amplicon sequencing of the hypervariable V3-V4 regions of the 16S rRNA gene. The skeletal muscle mass, subcutaneous and visceral fat levels were assessed with abdominal computed tomography as skeletal muscle, subcutaneous and visceral fat indices (SMI, SFI and VFI).<br><br>RESULTS: Patients with sarcopenia had more relative abundance (RA) of Agathobacter, Anaerostipes, Butyricicoccus, Dorea, Eggerthella, Microbacteriaceae, Veillonella and less RA of Akkermansiaceae, Akkermansia muciniphila, Verrucomicrobiae and Bilophila compared to patients with normal muscle mass. SMI directly correlated with RA of Akkermansia, Alistipes indistinctus, Anaerotruncus, Atopobiaceae, Bacteroides clarus, Bacteroides salyersiae, Barnesiellaceae, Bilophila wadsworthia, Pseudomonadota, Olsenella, and Parabacteroides distasonis, and negatively correlated with RA of Anaerostipes and Eggerthella. Sarcopenia was detected in 20.0% patients whose gut microbiota had Akkermansia but not Eggerthella, and in all the patients, whose gut microbiota had Eggerthella but not Akkermansia. The Akkermansia and Eggerthella abundances were independent determinants of SMI. RA of Akkermansia, Akkermansia muciniphila, Akkermansiaceae, Bacteroides salyersiae, Barnesiella, Bilophila, Desulfobacterota, Verrucomicrobiota and other taxa correlated positively and RA of Anaerovoracaceae, Elusimicrobiaceae, Elusimicrobium, Kiritimatiellae, Spirochaetota, and other taxa correlated negatively with the SFI. RA of Alistripes, Romboutsia, Succinivibrio, and Succinivibrionaceae correlated positively and RA of Bacteroides thetaiotaomicron correlated negatively with VFI.<br><br>CONCLUSION: The muscle mass level in cirrhosis correlates with the abundance of several gut microbiota taxa, of which Akkermansia and Eggerthella seems to be the most important.}, }
@article {pmid39534501, year = {2024}, author = {Koh, H}, title = {A general kernel machine regression framework using principal component analysis for jointly testing main and interaction effects: Applications to human microbiome studies.}, journal = {NAR genomics and bioinformatics}, volume = {6}, number = {4}, pages = {lqae148}, pmid = {39534501}, issn = {2631-9268}, abstract = {The effect of a treatment on a health or disease response can be modified by genetic or microbial variants. It is the matter of interaction effects between genetic or microbial variants and a treatment. To powerfully discover genetic or microbial biomarkers, it is crucial to incorporate such interaction effects in addition to the main effects. However, in the context of kernel machine regression analysis of its kind, existing methods cannot be utilized in a situation, where a kernel is available but its underlying real variants are unknown. To address such limitations, I introduce a general kernel machine regression framework using principal component analysis for jointly testing main and interaction effects. It begins with extracting principal components from an input kernel through the singular value decomposition. Then, it employs the principal components as surrogate variants to construct three endogenous kernels for the main effects, interaction effects, and both of them, respectively. Hence, it works with a kernel as an input without knowing its underlying real variants, and also detects either the main effects, interaction effects, or both of them robustly. I also introduce its omnibus testing extension to multiple input kernels, named OmniK. I demonstrate its use for human microbiome studies.}, }
@article {pmid39526038, year = {2024}, author = {Feng, C and Jia, H and Wang, H and Wang, J and Lin, M and Hu, X and Yu, C and Song, H and Wang, L}, title = {MicroNet-MIMRF: a microbial network inference approach based on mutual information and Markov random fields.}, journal = {Bioinformatics advances}, volume = {4}, number = {1}, pages = {vbae167}, pmid = {39526038}, issn = {2635-0041}, abstract = {MOTIVATION: The human microbiome, comprises complex associations and communication networks among microbial communities, which are crucial for maintaining health. The construction of microbial networks is vital for elucidating these associations. However, existing microbial networks inference methods cannot solve the issues of zero-inflation and non-linear associations. Therefore, necessitating novel methods to improve the accuracy of microbial networks inference.<br><br>RESULTS: In this study, we introduce the Microbial Network based on Mutual Information and Markov Random Fields (MicroNet-MIMRF) as a novel approach for inferring microbial networks. Abundance data of microbes are modeled through the zero-inflated Poisson distribution, and the discrete matrix is estimated for further calculation. Markov random fields based on mutual information are used to construct accurate microbial networks. MicroNet-MIMRF excels at estimating pairwise associations between microbes, effectively addressing zero-inflation and non-linear associations in microbial abundance data. It outperforms commonly used techniques in simulation experiments, achieving area under the curve values exceeding 0.75 for all parameters. A case study on inflammatory bowel disease data further demonstrates the method's ability to identify insightful associations. Conclusively, MicroNet-MIMRF is a powerful tool for microbial network inference that handles the biases caused by zero-inflation and overestimation of associations.<br><br>The MicroNet-MIMRF is provided at https://github.com/Fionabiostats/MicroNet-MIMRF.}, }
@article {pmid39531852, year = {2025}, author = {Simbirtseva, KY and O'Toole, PW}, title = {Healthy and Unhealthy Aging and the Human Microbiome.}, journal = {Annual review of medicine}, volume = {76}, number = {1}, pages = {115-127}, doi = {10.1146/annurev-med-042423-042542}, pmid = {39531852}, issn = {1545-326X}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Aging/physiology ; Healthy Aging/physiology ; Dysbiosis ; }, abstract = {An altered gut microbiome is a feature of many multifactorial diseases, and microbiome effects on host metabolism, immune function, and possibly neurological function are implicated. Increased biological age is accompanied by a change in the gut microbiome. However, age-related health loss does not occur uniformly across all subjects but rather depends on differential loss of gut commensals and gain of pathobionts. In this article, we summarize the known and possible effects of the gut microbiome on the hallmarks of aging and describe the most plausible mechanisms. Understanding and targeting these factors could lead to prolonging health span by rationally maintaining the gut microbiome.}, }
@article {pmid39529240, year = {2024}, author = {Liu, S and Zhang, Z and Wang, X and Ma, Y and Ruan, H and Wu, X and Li, B and Mou, X and Chen, T and Lu, Z and Zhao, W}, title = {Biosynthetic potential of the gut microbiome in longevous populations.}, journal = {Gut microbes}, volume = {16}, number = {1}, pages = {2426623}, pmid = {39529240}, issn = {1949-0984}, mesh = {*Gastrointestinal Microbiome ; Humans ; *Feces/microbiology ; Aged ; *Metagenomics ; Multigene Family ; Aged, 80 and over ; Terpenes/metabolism ; Longevity ; Akkermansia/metabolism ; Adult ; Male ; Female ; Middle Aged ; Cohort Studies ; Biological Products/metabolism ; Metagenome ; Young Adult ; }, abstract = {Gut microbiome plays a pivotal role in combating diseases and facilitating healthy aging, and natural products derived from biosynthetic gene clusters (BGCs) of the human microbiome exhibit significant biological activities. However, the natural products of the gut microbiome in long-lived populations remain poorly understood. Here, we integrated six cohorts of long-lived populations, encompassing a total of 1029 fecal metagenomic samples, and employed the metagenomic single sample assembled BGCs (MSSA-BGCs) analysis pipeline to investigate the natural products and their associated species. Our findings reveal that the BGC composition of the extremely long-lived group differed significantly from that of younger elderly and young individuals across five cohorts. Terpene and Type I PKS BGCs were enriched in the extremely long-lived, whereas cyclic-lactone-autoinducer BGCs were more prevalent in the young. Association analysis indicated that terpene BGCs were strongly associated with the abundance of Akkermansia muciniphila, which was also more abundant in the long-lived elderly across at least three cohorts. We assembled 18 A. muciniphila draft genomes using metagenomic data from the extremely long-lived group across six cohorts and discovered that they all harbor two classes of terpene BGCs, which aligns with the 97 complete genomes of A. muciniphila strains retrieved from the NCBI database. The core domains of these two BGC classes are squalene/phytoene synthases involved in the biosynthesis of tri- and tetraterpenes. Furthermore, the abundance of fecal A. muciniphila was significantly associated with eight types of triterpenoids. Targeted terpenoid metabolomic analysis revealed that two triterpenoids, Holstinone C and colubrinic acid, were enriched in the A. muciniphila culture solution compared to the medium, thereby confirming the production of triterpenoids by A. muciniphila. The natural products derived from the gut of long-lived populations provide intriguing indications of their potential beneficial roles in regulating health.}, }
@article {pmid39512939, year = {2024}, author = {Costa, CFFA and Correia-de-Sá, T and Araujo, R and Barbosa, F and Burnet, PWJ and Ferreira-Gomes, J and Sampaio-Maia, B}, title = {The oral-gut microbiota relationship in healthy humans: identifying shared bacteria between environments and age groups.}, journal = {Frontiers in microbiology}, volume = {15}, number = {}, pages = {1475159}, pmid = {39512939}, issn = {1664-302X}, abstract = {INTRODUCTION: Although the oral cavity and the gut are anatomically continuous regions of the gastrointestinal tract, research on the relationship between oral and gut microbiota remains sparse. Oral-gut bacterial translocation is mostly studied in pathological contexts, thus evidence of translocation in healthy conditions is still scarce. Studying the oral-gut microbiota relationship in humans in different life stages is necessary in order to understand how these microbial communities might relate throughout life.<br><br>METHODS: In this study, saliva and fecal samples were collected from healthy participants (39 children, 97 adults). Microbiota analysis was carried out by sequencing the V4 region of the 16S ribosomal RNA gene, followed by amplicon sequence variant (ASV) analysis.<br><br>RESULTS AND DISCUSSION: Although the oral and gut microbiota are vastly different, a subset of 61 ASVs were present in both the oral cavity and gut of the same individual, and represented 1.6% of all ASVs detected. From these, 26 ASVs (classified into 18 genera: Actinomyces, Rothia, Bacteroides, Porphyromonas, Prevotella, Alistipes, Fusobacterium, Neisseria, Haemophilus, Akkermansia, Solobacterium, Granulicatella, Streptococcus, Gemella, Mogibacterium, Dialister, Veillonella, Christensenellaceae R-7 group) were present in both children and adults, suggesting the possibility of persistent colonization of both habitats by these microorganisms, initiating in childhood. Additionally, 62% of shared ASVs were more abundant in the oral cavity, indicating that oral-to-gut translocation may be the main route of translocation between environments, and highlighting that this phenomenon might be more common than previously thought in healthy individuals of all ages.}, }
@article {pmid39507669, year = {2024}, author = {Buytaers, FE and Berger, N and Van der Heyden, J and Roosens, NHC and De Keersmaecker, SCJ}, title = {The potential of including the microbiome as biomarker in population-based health studies: methods and benefits.}, journal = {Frontiers in public health}, volume = {12}, number = {}, pages = {1467121}, pmid = {39507669}, issn = {2296-2565}, mesh = {Humans ; *Biomarkers/analysis ; *Microbiota ; Population Health ; Health Status ; Public Health ; }, abstract = {The key role of our microbiome in influencing our health status, and its relationship with our environment and lifestyle or health behaviors, have been shown in the last decades. Therefore, the human microbiome has the potential to act as a biomarker or indicator of health or exposure to health risks in the general population, if information on the microbiome can be collected in population-based health surveys or cohorts. It could then be associated with epidemiological participant data such as demographic, clinical or exposure profiles. However, to our knowledge, microbiome sampling has not yet been included as biological evidence of health or exposure to health risks in large population-based studies representative of the general population. In this mini-review, we first highlight some practical considerations for microbiome sampling and analysis that need to be considered in the context of a population study. We then present some examples of topics where the microbiome could be included as biological evidence in population-based health studies for the benefit of public health, and how this could be developed in the future. In doing so, we aim to highlight the benefits of having microbiome data available at the level of the general population, combined with epidemiological data from health surveys, and hence how microbiological data could be used in the future to assess human health. We also stress the challenges that remain to be overcome to allow the use of this microbiome data in order to improve proactive public health policies.}, }
@article {pmid39506745, year = {2024}, author = {Liechty, ZS and Agans, RT and Barbato, RA and Colston, SM and Christian, MR and Hammamieh, R and Kardish, MR and Karl, JP and Leary, DH and Mauzy, CA and de Goodfellow, IP and Racicot, K and Soares, JW and Stamps, BW and Sweet, CR and Tuck, SM and Whitman, JA and Goodson, MS}, title = {Meeting report of the seventh annual Tri-Service Microbiome Consortium Symposium.}, journal = {BMC proceedings}, volume = {18}, number = {Suppl 20}, pages = {25}, pmid = {39506745}, issn = {1753-6561}, abstract = {The Tri-Service Microbiome Consortium (TSMC) was founded to enhance collaboration, coordination, and communication of microbiome research among DoD organizations and to facilitate resource, material and information sharing among consortium members, which includes collaborators in academia and industry. The 2023 annual symposium was a hybrid meeting held in Washington DC on 26-27 September 2023 concurrent with the virtual attendance, with oral and poster presentations and discussions centered on microbiome-related topics within five broad thematic areas: 1) Environmental Microbiome Characterization; 2) Microbiome Analysis; 3) Human Microbiome Characterization; 4) Microbiome Engineering; and 5) In Vitro and In Vivo Microbiome Models. Collectively, the symposium provided an update on the scope of current DoD and DoD-affiliated microbiome research efforts and fostered collaborative opportunities. This report summarizes the presentations and outcomes of the 7th annual TSMC symposium.}, }
@article {pmid39505797, year = {2024}, author = {Ji, Y and Sun, H and Wang, Y and Li, Y and Piao, R and Bu, L and Xu, H}, title = {Characterizing the oral and gastrointestinal microbiome associated with healthy aging: insights from long-lived populations in Northeastern China.}, journal = {GeroScience}, volume = {}, number = {}, pages = {}, pmid = {39505797}, issn = {2509-2723}, support = {2022JH2/101300031//Natural Science Foundation of Liaoning Province/ ; 2020YFA0907800//Ministry of Science and Technology of the People's Republic of China/ ; 22-322-3-05//Natural Science Foundation of Shenyang Municipality/ ; }, abstract = {The oral and gastrointestinal (GI) tract microbiota in humans is susceptible to geographical influences and represents vital factors impacting healthy aging. The northeastern region of China, characterized by distinct dietary and climatic conditions, significantly influences the human microbiome composition. However, the microbial structure of the entire long-lived population in this area has not been evaluated. This study recruited a cohort of 142 individuals aged 55-102 residing in Northeast China, and their oral and gut microbiota were evaluated using full-length 16S rRNA gene amplicon sequencing. The results indicate that the oral and GI tract microbiota of long-lived individuals showed reduced microbial taxonomic richness and evenness compared to sub-longevity individuals. With aging, the core species experience a gradual decline in abundance, while subordinate species show an increase. The long-lived population exhibited a heightened ability to enrich beneficial bacteria including Akkermansia, Alistipes, Parabacteroides, and Eubacterium coprostanoligenes in the GI tract, which are associated with host metabolism and have the potential to act as probiotics, reducing the risks of unhealthy aging in the northeast population. Bifidobacterium sp. and Lactobacillus salivarius have been found to coexist in both the oral cavity and the GI tract of long-lived individuals. We hypothesize that beneficial bacterial taxa from the oral cavity colonize the GI tract more extensively in long-lived individuals compared to those with a shorter lifespan. These findings pave the way for identifying probiotic strains that can promote healthy aging in Northeast China.}, }
@article {pmid39505118, year = {2024}, author = {Ferrara, F and Valacchi, G}, title = {Role of microbiota in the GUT-SKIN AXIS responses to outdoor stressors.}, journal = {Free radical biology &amp; medicine}, volume = {225}, number = {}, pages = {894-909}, doi = {10.1016/j.freeradbiomed.2024.11.003}, pmid = {39505118}, issn = {1873-4596}, mesh = {Humans ; *Skin/microbiology/immunology ; *Gastrointestinal Microbiome ; *Oxidative Stress ; Dysbiosis/microbiology/immunology ; Air Pollutants/adverse effects ; Microbiota ; Animals ; }, abstract = {Beside the respiratory tract, the skin and the gut represent the first defensive lines of our body against the external insults displaying many important biochemical features able to maintain the epithelial barrier integrity and to regulate the tissue immune responses. The human microbiome is essential in maintaining the tissue homeostasis and its dysregulation may lead to tissue conditions including inflammatory pathologies. Among all external insults, air pollutants have been shown to cause oxidative stress damage within the target tissues via an OxInflammatory response. Dysregulation of the gut microbiome (dysbiosis) by outdoor stressors, including air pollutants, may promote the exacerbation of the skin tissue damage via the interplay between the gut-skin axis. The intent of this review is to highlight the ability of exogenous stressors to modulate the human gut-skin axis via a redox regulated mechanism affecting the microbiome and therefore contributing to the development and aggravation of gut and skin conditions.}, }
@article {pmid39504483, year = {2024}, author = {Chen, H and Chen, K}, title = {Predicting disease-associated microbes based on similarity fusion and deep learning.}, journal = {Briefings in bioinformatics}, volume = {25}, number = {6}, pages = {}, pmid = {39504483}, issn = {1477-4054}, support = {20242BAB25083//Jiangxi Provincial Natural Science Foundation, China/ ; }, mesh = {*Deep Learning ; Humans ; *Computational Biology/methods ; *Microbiota/genetics ; Algorithms ; }, abstract = {Increasing studies have revealed the critical roles of human microbiome in a wide variety of disorders. Identification of disease-associated microbes might improve our knowledge and understanding of disease pathogenesis and treatment. Computational prediction of microbe-disease associations would provide helpful guidance for further biomedical screening, which has received lots of research interest in bioinformatics. In this study, a deep learning-based computational approach entitled SGJMDA is presented for predicting microbe-disease associations. Specifically, SGJMDA first fuses multiple similarities of microbes and diseases using a nonlinear strategy, and extracts feature information from homogeneous networks composed of the fused similarities via a graph convolution network. Second, a heterogeneous microbe-disease network is built to further capture the structural information of microbes and diseases by employing multi-neighborhood graph convolution network and jumping knowledge network. Finally, potential microbe-disease associations are inferred through computing the linear correlation coefficients of their embeddings. Results from cross-validation experiments show that SGJMDA outperforms 6 state-of-the-art computational methods. Furthermore, we carry out case studies on three important diseases using SGJMDA, in which 19, 20, and 11 predictions out of their top 20 results are successfully checked by the latest databases, respectively. The excellent performance of SGJMDA suggests that it could be a valuable and promising tool for inferring disease-associated microbes.}, }
@article {pmid39484071, year = {2024}, author = {Nurkolis, F and Utami, TW and Alatas, AI and Wicaksono, D and Kurniawan, R and Ratmandhika, SR and Sukarno, KT and Pahu, YGP and Kim, B and Tallei, TE and Tjandrawinata, RR and Alhasyimi, AA and Surya, R and Helen, H and Halim, P and Muhar, AM and Syahputra, RA}, title = {Can salivary and skin microbiome become a biodetector for aging-associated diseases? Current insights and future perspectives.}, journal = {Frontiers in aging}, volume = {5}, number = {}, pages = {1462569}, pmid = {39484071}, issn = {2673-6217}, abstract = {Growth and aging are fundamental elements of human development. Aging is defined by a decrease in physiological activities and higher illness vulnerability. Affected by lifestyle, environmental, and hereditary elements, aging results in disorders including cardiovascular, musculoskeletal, and neurological diseases, which accounted for 16.1 million worldwide deaths in 2019. Stress-induced cellular senescence, caused by DNA damage, can reduce tissue regeneration and repair, promoting aging. The root cause of many age-related disorders is inflammation, encouraged by the senescence-associated secretory phenotype (SASP). Aging's metabolic changes and declining immune systems raise illness risk via promoting microbiome diversity. Stable, individual-specific skin and oral microbiomes are essential for both health and disease since dysbiosis is linked with periodontitis and eczema. Present from birth to death, the human microbiome, under the influence of diet and lifestyle, interacts symbiotically with the body. Poor dental health has been linked to Alzheimer's and Parkinson's diseases since oral microorganisms and systemic diseases have important interactions. Emphasizing the importance of microbiome health across the lifetime, this study reviews the understanding of the microbiome's role in aging-related diseases that can direct novel diagnosis and treatment approaches.}, }
@article {pmid39483755, year = {2024}, author = {Pita, S and Myers, PN and Johansen, J and Russel, J and Nielsen, MC and Eklund, AC and Nielsen, HB}, title = {CHAMP delivers accurate taxonomic profiles of the prokaryotes, eukaryotes, and bacteriophages in the human microbiome.}, journal = {Frontiers in microbiology}, volume = {15}, number = {}, pages = {1425489}, pmid = {39483755}, issn = {1664-302X}, abstract = {INTRODUCTION: Accurate taxonomic profiling of the human microbiome composition is crucial for linking microbial species to health outcomes. Therefore, we created the Clinical Microbiomics Human Microbiome Profiler (CHAMP), a comprehensive tool designed for the profiling of prokaryotes, eukaryotes, and viruses across all body sites.<br><br>METHODS: CHAMP uses a reference database derived from 30,382 human microbiome samples, covering 6,567 prokaryotic and 244 eukaryotic species, as well as 64,003 viruses. We benchmarked CHAMP against established profiling tools (MetaPhlAn 4, Bracken 2, mOTUs 3, and Phanta) using a diverse set of in silico metagenomes and DNA mock communities.<br><br>RESULTS: CHAMP demonstrated unparalleled species recall, F1 score, and significantly reduced false positives compared to all other tools benchmarked. The false positive relative abundance (FPRA) for CHAMP was, on average, 50-fold lower than the second-best performing profiler. CHAMP also proved to be more robust than other tools at low sequencing depths, highlighting its application for low biomass samples.<br><br>DISCUSSION: Taken together, this establishes CHAMP as a best-in-class human microbiome profiler of prokaryotes, eukaryotes, and viruses in diverse and complex communities across low and high biomass samples. CHAMP profiling is offered as a service by Clinical Microbiomics A/S and is available for a fee at https://cosmosidhub.com.}, }
@article {pmid39486524, year = {2024}, author = {Kapoor, B and Biswas, P and Gulati, M and Rani, P and Gupta, R}, title = {Gut microbiome and Alzheimer's disease: What we know and what remains to be explored.}, journal = {Ageing research reviews}, volume = {102}, number = {}, pages = {102570}, doi = {10.1016/j.arr.2024.102570}, pmid = {39486524}, issn = {1872-9649}, mesh = {Animals ; Humans ; *Alzheimer Disease/metabolism/microbiology/physiopathology ; Brain/metabolism/physiopathology ; *Brain-Gut Axis/physiology ; *Dysbiosis/microbiology/physiopathology ; *Gastrointestinal Microbiome/physiology ; }, abstract = {With advancement in human microbiome research, an increasing number of scientific evidences have endorsed the key role of gut microbiota in the pathogenesis of Alzheimer disease. Microbiome dysbiosis, characterized by altered diversity and composition, as well as rise of pathobionts influence not only various gut disorder but also central nervous system disorders such as AD. On the basis of accumulated evidences of past few years now it is quite clear that the gut microbiota can control the functions of the central nervous system (CNS) through the gut-brain axis, which provides a new prospective into the interactions between the gut and brain. The main focus of this review is on the molecular mechanism of the crosstalk between the gut microbiota and the brain through the gut-brain axis, and on the onset and development of neurological disorders triggered by the dysbiosis of gut microbiota. Due to microbiota dysbiosis the permeability of the gut and blood brain barrier is increased which may mediate or affect AD. Along with this, bacterial population of the gut microbiota can secrete amyloid proteins and lipopolysaccharides in a large quantity which may create a disturbance in the signaling pathways and the formation of proinflammatory cytokines associated with the pathogenesis of AD. These topics are followed by a critical analysis of potential intervention strategies targeting gut microbiota dysbiosis, including the use of probiotics, prebiotics, metabolites, diets and fecal microbiota transplantation. The main purpose of this review includes the summarization and discussion on the recent finding that may explain the role of the gut microbiota in the development of AD. Understanding of these fundamental mechanisms may provide a new insight into the novel therapeutic strategies for AD.}, }
@article {pmid39481381, year = {2024}, author = {Zheludev, IN and Edgar, RC and Lopez-Galiano, MJ and de la Peña, M and Babaian, A and Bhatt, AS and Fire, AZ}, title = {Viroid-like colonists of human microbiomes.}, journal = {Cell}, volume = {187}, number = {23}, pages = {6521-6536.e18}, doi = {10.1016/j.cell.2024.09.033}, pmid = {39481381}, issn = {1097-4172}, mesh = {Humans ; *Microbiota/genetics ; *Phylogeny ; Feces/microbiology ; RNA, Circular/genetics/metabolism ; Open Reading Frames/genetics ; RNA, Catalytic/metabolism/genetics ; Gastrointestinal Microbiome/genetics ; }, abstract = {Here, we describe "obelisks," a class of heritable RNA elements sharing several properties: (1) apparently circular RNA ∼1 kb genome assemblies, (2) predicted rod-like genome-wide secondary structures, and (3) open reading frames encoding a novel "Oblin" protein superfamily. A subset of obelisks includes a variant hammerhead self-cleaving ribozyme. Obelisks form their own phylogenetic group without detectable similarity to known biological agents. Surveying globally, we identified 29,959 distinct obelisks (clustered at 90% sequence identity) from diverse ecological niches. Obelisks are prevalent in human microbiomes, with detection in ∼7% (29/440) and ∼50% (17/32) of queried stool and oral metatranscriptomes, respectively. We establish Streptococcus sanguinis as a cellular host of a specific obelisk and find that this obelisk's maintenance is not essential for bacterial growth. Our observations identify obelisks as a class of diverse RNAs of yet-to-be-determined impact that have colonized and gone unnoticed in human and global microbiomes.}, }
@article {pmid39479472, year = {2024}, author = {Mousa, WK and Shaikh, AY and Ghemrawi, R and Aldulaimi, M and Al Ali, A and Sammani, N and Khair, M and Helal, MI and Al-Marzooq, F and Oueis, E}, title = {Human microbiome derived synthetic antimicrobial peptides with activity against Gram-negative, Gram-positive, and antibiotic resistant bacteria.}, journal = {RSC medicinal chemistry}, volume = {16}, number = {1}, pages = {312-323}, pmid = {39479472}, issn = {2632-8682}, abstract = {The prevalence of antibacterial resistance has become one of the major health threats of modern times, requiring the development of novel antibacterials. Antimicrobial peptides are a promising source of antibiotic candidates, mostly requiring further optimization to enhance druggability. In this study, a series of new antimicrobial peptides derived from lactomodulin, a human microbiome natural peptide, was designed, synthesized, and biologically evaluated. Within the most active region of the parent peptide, linear peptide LM6 with the sequence LSKISGGIGPLVIPV-NH2 and its cyclic derivatives LM13a and LM13b showed strong antibacterial activity against Gram-positive bacteria, including resistant strains, and Gram-negative bacteria. The peptides were found to have a rapid onset of bactericidal activity and transmission electron microscopy clearly shows the disintegration of the cell membrane, suggesting a membrane-targeting mode of action.}, }
@article {pmid39478225, year = {2024}, author = {Lu, Z and Mo, S and Xie, D and Zhai, X and Deng, S and Zhou, K and Wang, K and Kang, X and Zhang, H and Tong, J and Hou, L and Hu, H and Li, X and Zhou, D and Lee, LTO and Liu, L and Zhu, Y and Yu, J and Lan, P and Wang, J and He, Z and He, X and Hu, Z}, title = {Polyclonal-to-monoclonal transition in colorectal precancerous evolution.}, journal = {Nature}, volume = {636}, number = {8041}, pages = {233-240}, pmid = {39478225}, issn = {1476-4687}, mesh = {Animals ; Humans ; Male ; Mice ; Carcinogenesis/genetics/pathology ; *Cell Lineage ; Cell Transformation, Neoplastic/genetics/pathology ; *Clonal Evolution ; *Clone Cells/metabolism ; Colonic Polyps/pathology/genetics ; *Colorectal Neoplasms/genetics/pathology ; Disease Models, Animal ; DNA Barcoding, Taxonomic ; Exome Sequencing ; Genes, APC ; Inflammation/pathology/genetics ; *Precancerous Conditions/genetics/pathology ; *Single-Cell Analysis ; Single-Cell Gene Expression Analysis ; Whole Genome Sequencing ; Intestines/cytology/pathology ; }, abstract = {Unravelling the origin and evolution of precancerous lesions is crucial for effectively preventing malignant transformation, yet our current knowledge remains limited[1-3]. Here we used a base editor-enabled DNA barcoding system[4] to comprehensively map single-cell phylogenies in mouse models of intestinal tumorigenesis induced by inflammation or loss of the Apc gene. Through quantitative analysis of high-resolution phylogenies including 260,922 single cells from normal, inflamed and neoplastic intestinal tissues, we identified tens of independent cell lineages undergoing parallel clonal expansions within each lesion. We also found polyclonal origins of human sporadic colorectal polyps through bulk whole-exome sequencing and single-gland whole-genome sequencing. Genomic and clinical data support a model of polyclonal-to-monoclonal transition, with monoclonal lesions representing a more advanced stage. Single-cell RNA sequencing revealed extensive intercellular interactions in early polyclonal lesions, but there was significant loss of interactions during monoclonal transition. Therefore, our data suggest that colorectal precancer is often founded by many different lineages and highlight their cooperative interactions in the earliest stages of cancer formation. These findings provide insights into opportunities for earlier intervention in colorectal cancer.}, }
@article {pmid39478172, year = {2024}, author = {Collado, MC and Devkota, S and Ghosh, TS}, title = {Gut microbiome: a biomedical revolution.}, journal = {Nature reviews. Gastroenterology &amp; hepatology}, volume = {21}, number = {12}, pages = {830-833}, pmid = {39478172}, issn = {1759-5053}, }
@article {pmid39474048, year = {2023}, author = {Wu, J and Zhang, S and Chen, Y and Zhao, J and Prosun, T and O'Brien, JW and Mueller, JF and Tscharke, BJ and Coin, LJM and Luby, SP and Hai, FI and Buchanan, T and Jiang, G}, title = {Associations between Wastewater Microbiome and Population Smoking Rate Identified Using Wastewater-Based Epidemiology.}, journal = {Environment &amp; health (Washington, D.C.)}, volume = {1}, number = {6}, pages = {394-404}, pmid = {39474048}, issn = {2833-8278}, abstract = {Tobacco use is known to cause health damage, partly by changing the mouth, respiratory tract, and gut-related microbiomes. This study aims to identify the associations between the human microbiome detected in domestic wastewater and the population smoking rate. Metagenomic sequencing and a biomarker discovery algorithm were employed to identify microorganisms as potential microbial biomarkers of smoking through wastewater-based epidemiology. Wastewater samples were collected from selected catchments with low and high smoking rates, i.e., 11.2 ± 1.5% and 17.0 ± 1.6%, respectively. Using the linear discriminant analysis effect size (LEfSe) method, Neisseria, Desulfovibrio, Megamonas, Blautia, Fusicatenibacter, Granulicatella and Enterococcus were suggested as potential biomarker microorganisms. A higher abundance of pathogens, including Neisseria, Eikenella and Haemophilus, was associated with the high smoking rate, likely because of their colonization in smoking-disturbed human guts. The identified potential microbial biomarkers reflect the change of the human gut microbiome due to the long-term smoking behavior. The metagenomic analysis also indicates that smoking upregulates microbial gene expression of genetic information processing, environmental information processing, and cell wall peptidoglycan cleavage, while it downregulates amino acid, lipid, and galactose metabolisms. The findings demonstrate the potential of microbial biomarkers for the surveillance of smoking through a wastewater-based epidemiology approach.}, }
@article {pmid39472801, year = {2024}, author = {Valiei, A and Dickson, AM and Aminian-Dehkordi, J and Mofrad, MRK}, title = {Bacterial community dynamics as a result of growth-yield trade-off and multispecies metabolic interactions toward understanding the gut biofilm niche.}, journal = {BMC microbiology}, volume = {24}, number = {1}, pages = {441}, pmid = {39472801}, issn = {1471-2180}, mesh = {*Bacteria/metabolism/classification/growth &amp; development/genetics ; *Biofilms/growth &amp; development ; Humans ; *Gastrointestinal Microbiome ; Microbial Interactions ; Bacterial Physiological Phenomena ; Models, Biological ; Kinetics ; Symbiosis ; Ecosystem ; Nutrients/metabolism ; }, abstract = {Bacterial communities are ubiquitous, found in natural ecosystems, such as soil, and within living organisms, like the human microbiome. The dynamics of these communities in diverse environments depend on factors such as spatial features of the microbial niche, biochemical kinetics, and interactions among bacteria. Moreover, in many systems, bacterial communities are influenced by multiple physical mechanisms, such as mass transport and detachment forces. One example is gut mucosal communities, where dense, closely packed communities develop under the concurrent influence of nutrient transport from the lumen and fluid-mediated detachment of bacteria. In this study, we model a mucosal niche through a coupled agent-based and finite-volume modeling approach. This methodology enables us to model bacterial interactions affected by nutrient release from various sources while adjusting individual bacterial kinetics. We explored how the dispersion and abundance of bacteria are influenced by biochemical kinetics in different types of metabolic interactions, with a particular focus on the trade-off between growth rate and yield. Our findings demonstrate that in competitive scenarios, higher growth rates result in a larger share of the niche space. In contrast, growth yield plays a critical role in neutralism, commensalism, and mutualism interactions. When bacteria are introduced sequentially, they cause distinct spatiotemporal effects, such as deeper niche colonization in commensalism and mutualism scenarios driven by species intermixing effects, which are enhanced by high growth yields. Moreover, sub-ecosystem interactions dictate the dynamics of three-species communities, sometimes yielding unexpected outcomes. Competitive, fast-growing bacteria demonstrate robust colonization abilities, yet they face challenges in displacing established mutualistic systems. Bacteria that develop a cooperative relationship with existing species typically obtain niche residence, regardless of their growth rates, although higher growth yields significantly enhance their abundance. Our results underscore the importance of bacterial niche dynamics in shaping community properties and succession, highlighting a new approach to manipulating microbial systems.}, }
@article {pmid39470277, year = {2024}, author = {Xie, J and Zhang, X and Cheng, L and Deng, Y and Ren, H and Mu, M and Zhao, L and Mu, C and Chen, J and Liu, K and Ma, R}, title = {Integrated multi-omics analysis of the microbial profile characteristics associated with pulmonary arterial hypertension in congenital heart disease.}, journal = {Microbiology spectrum}, volume = {12}, number = {12}, pages = {e0180824}, pmid = {39470277}, issn = {2165-0497}, abstract = {Dysregulation of immune and inflammatory cells around blood vessels and metabolic dysfunction are key mechanisms in the development of pulmonary arterial hypertension (PAH). The homeostasis of the human microbiome plays a crucial role in regulating immune responses and the progression of diseases. For pulmonary arterial hypertension associated with congenital heart disease involving body-lung shunt (PAH-CHD), the potential impact of the microbiome on the "gut-lung axis" remains underexplored. This study recruited 15 healthy individuals and 15 patients with pulmonary arterial hypertension due to congenital heart disease from Fuwai Yunnan Hospital, Chinese Academy of Medical Sciences, and Kunming Children's Hospital. We performed differential analyses of metabolites and microbiota from both the gut and lower respiratory tract for these two groups. The goal was to investigate the "gut-lung axis" microbiome and metabolome profiles in children with PAH-CHD and to analyze the interrelationships between these profiles. Ultimately, we aim to propose the potential value of these profiles in aiding diagnosis. The results indicated that the gut and pulmonary microbiota of children with PAH-CHD are characterized by an increased abundance of beneficial symbionts, which are closely linked to changes in the metabolome. Metabolite functional enrichment analysis revealed energy metabolism reprogramming in the PAH-CHD group, with active metabolic pathways associated with bile acid secretion and carnitine homeostasis. Moreover, the differential expression of metabolites was correlated with right heart function and growth development.IMPORTANCEPrevious studies have primarily focused on the relationship between the gut microbiome and PAH. However, the impact of microbial homeostasis on the progression of PAH-CHD from the perspective of the gut-lung axis has not been adequately elucidated. Our study utilizes an integrated multi-omics approach to report on the differential characteristics of gut and lung microbiota between children with PAH-CHD and reference subjects. We found that microbiota influence the pathological changes and disease manifestations of PAH-CHD through their metabolic activity. Additionally, alterations in metabolites impact the microbial ecological structure. Our findings suggest that modulating the microbiome composition may have positive implications for maintaining and regulating the immune environment and pathological progression of PAH-CHD.}, }
@article {pmid39470241, year = {2024}, author = {Bouchier, C and Touak, G and Rei, D and Clermont, D}, title = {Complete genome sequence of two Christensenella minuta strains CIP 112228 and CIP 112229, isolated from human fecal samples.}, journal = {Microbiology resource announcements}, volume = {13}, number = {12}, pages = {e0076624}, pmid = {39470241}, issn = {2576-098X}, abstract = {Christensenella minuta is one of the representative bacterial species of the human gut microbiome. We report the complete genome sequence of two strains, Christensenella minuta CIP 112228 and CIP 112229, isolated from two healthy volunteers.}, }
@article {pmid39470240, year = {2024}, author = {Dumann, G and Rohland, O and Abdel-Glil, MY and Allen, RJ and Bauer, M and Busch, A}, title = {Draft genomes of the bile duct microbiome strains Klebsiella pneumoniae and Enterococcus lactis isolated from bilioenteric drainages with biofilm-forming abilities.}, journal = {Microbiology resource announcements}, volume = {13}, number = {12}, pages = {e0020224}, pmid = {39470240}, issn = {2576-098X}, support = {EXC 2051 - Project-ID 390713860//Deutsche Forschungsgemeinschaft (DFG)/ ; }, abstract = {We describe the genetic properties of two strains isolated from the elusive bile duct microbiome from solid organ transplant patients. Bacterial strains Enterococcus lactis (MS-STENT-08-E-001) and Klebsiella pneumoniae (MS-STENT-01-M-001) were isolated from the biofilms of bile duct catheters.}, }
@article {pmid39470190, year = {2024}, author = {Toyomane, K and Kimura, Y and Fukagawa, T and Yamagishi, T and Watanabe, K and Akutsu, T and Asahi, A and Kubota, S and Sekiguchi, K}, title = {Metagenomic sequencing of CRISPRs as a new marker to aid in personal identification with low-biomass samples.}, journal = {mSystems}, volume = {9}, number = {11}, pages = {e0103824}, pmid = {39470190}, issn = {2379-5077}, support = {20K18991,24K20264//MEXT | Japan Society for the Promotion of Science (JSPS)/ ; }, mesh = {Humans ; *Clustered Regularly Interspaced Short Palindromic Repeats/genetics ; *Metagenomics/methods ; *Skin/microbiology ; Microbiota/genetics ; Sequence Analysis, DNA/methods ; Metagenome/genetics ; Genetic Markers/genetics ; }, abstract = {The high specificity of the human skin microbiome is expected to provide a new marker for personal identification. Metagenomic sequencing of clustered regularly interspaced short palindromic repeats (CRISPRs), which we call metaCRISPR typing, was shown to achieve personal identification accurately. However, the intra-individual variability observed in previous studies, which may be due to poor DNA yields from skin samples, has resulted in non-reproducible results. Furthermore, whether metaCRISPR typing can assist in the forensic human DNA analysis of low-biomass samples, from which the information obtained is insufficient, is unknown. In the present study, we sequenced serially diluted control streptococcal CRISPRs cloned into plasmids to determine the minimum copy number required to obtain reproducible results from metaCRISPR typing. We found that at least 10[2] copies of CRISPRs are necessary to obtain reproducible results. We then analyzed the skin swab samples using both metaCRISPR typing and human DNA typing. When the DNA extracted from the skin swabs was diluted, no information was obtained from six out of eight samples by human DNA typing. On the other hand, beta diversity indices of spacer sequences compared with reference samples were below 0.8 for three out of six samples, for which no information was obtained from human DNA analysis, indicating that the spacers observed in these samples were similar to those in the references. These results indicate that metaCRISPR typing may contribute to the identification of individuals from whom the samples were obtained, even in cases where human DNA yields are insufficient to perform human DNA analysis.IMPORTANCEPrevious studies have developed new personal identification methods utilizing personal differences in the skin microbiome. However, intra-individual diversity of skin microbiome may preclude the application of microbiome-based personal identification. Moreover, no study has compared microbiome-based personal identification and practical human DNA analysis. Here, we revealed that the results of metaCRISPR typing, a previously developed microbiome-based personal identification method, are stable if the copy number of the marker gene is sufficient. We then analyzed the skin swab samples using both metaCRISPR typing and human DNA analysis. Our results indicate that metaCRISPR typing may provide additional information for personal identification using low-biomass samples that cannot be used for conventional human DNA analysis.}, }
@article {pmid39466852, year = {2024}, author = {Chen, H and Huang, S and Yao, S and Wang, J and Huang, J and Yu, Z}, title = {Multi-omics analyses of Bacillus amyloliquefaciens treated mice infected with Schistosoma japonicum reveal dynamics change of intestinal microbiome and its associations with host metabolism.}, journal = {PLoS neglected tropical diseases}, volume = {18}, number = {10}, pages = {e0012583}, pmid = {39466852}, issn = {1935-2735}, mesh = {Animals ; Mice ; *Gastrointestinal Microbiome ; *Bacillus amyloliquefaciens/metabolism/genetics ; *Schistosoma japonicum/metabolism ; *Schistosomiasis japonica ; *Probiotics/administration &amp; dosage ; Female ; Multiomics ; }, abstract = {BACKGROUND: Schistosomiasis japonica is a serious threat to human health. It causes damage to the intestine and liver. Probiotic therapy has been shown to be effective in alleviating intestinal diseases and improving host health. Previous studies have found that Bacillus amyloliquefaciens could alleviate the pathological symptoms of schistosomiasis japonica, but the regulatory mechanism of alleviating schistosomiasis japonica is still unknown.<br><br>PRINCIPAL FINDINGS: This study analyzed the dynamic changes of intestinal microbiome in mice infected with Schistosoma japonicum after the intervention of B. amyloliquefaciens and its connection to host metabolism by multi-omics sequencing technology. B. amyloliquefaciens was found to significantly regulate the homeostasis of intestinal microbiota by promoting the growth of beneficial bacteria and inhibiting potential pathogenic bacteria and protect the number of core microbes. Meanwhile, the genes related to the metabolism of glycerophospholipids and amino acid from intestinal microbiome changed significantly, and were shown to be significantly positively correlated with the associated metabolites of microbial origin. Moreover, host metabolism (lipid metabolism and steroid hormone biosynthesis) was also found to be significantly regulated.<br><br>CONCLUSIONS: The recovery of intestinal microbial homeostasis and the regulation of host metabolism revealed the potential probiotic properties of B. amyloliquefaciens, which also provided new ideas for the prevention and adjuvant treatment of schistosomiasis japonica.}, }
@article {pmid39465215, year = {2024}, author = {Lam, MI and Gleason, K and Repp, AB and Yeo, S and Vojnits, K and MacNaughton, P and Pakpour, S}, title = {The spatial and temporal effect of electrochromic windows on indoor and human microbiome in an inpatient hospital.}, journal = {Antimicrobial stewardship &amp; healthcare epidemiology : ASHE}, volume = {4}, number = {1}, pages = {e188}, pmid = {39465215}, issn = {2732-494X}, abstract = {OBJECTIVE: Improving the hospital environment and developing novel disinfection strategies are critical for infection control in healthcare settings. In this study, we explored the effects of electrochromic (EC) windows on indoor and patient microbiome in an inpatient hospital.<br><br>PATIENT AND SETTING: Hematology-Oncology patients at the University of Vermont Medical Center.<br><br>METHODS: We conducted a prospective study in ten occupied patient rooms. Five of the patient rooms had active EC windows that tint dynamically to control for heat and glare, and the other five rooms had deactivated EC windows that simulated traditional windows and blinds. Samples were collected one day before patient admission as baseline and on the 1st, 3rd, and 5th day of the patient stay. Total bacterial abundance and bacterial community structure were determined through quantitative PCR and 16s rRNA Illumina MiSeq sequencing, respectively.<br><br>RESULTS: Patient rooms with active EC windows had significantly lower light intensity and temperature than traditional patient rooms with blinds. The absolute bacterial abundance and diversities on windows were significantly lower in rooms with EC windows and the bacterial composition changed after one day EC window activation. Compared to baseline, relative abundance of the Staphylococcus genus was significantly lower on EC window surface during the five-day experiment. In contrast, the air microbiome was more diverse in rooms with EC windows.<br><br>CONCLUSION: Active electrochromic (EC) windows in patient rooms result in lower light intensity and temperature, reduced bacterial abundance and diversities on window surfaces, and a more diverse air microbiome, informing future healthcare design.}, }
@article {pmid39458569, year = {2024}, author = {Toivio, L and Launonen, H and Lindén, J and Lehto, M and Vapaatalo, H and Salmenkari, H and Korpela, R}, title = {Correction: Toivio et al. Ketogenic Diet High in Saturated Fat Promotes Colonic Claudin Expression without Changes in Intestinal Permeability to Iohexol in Healthy Mice. Nutrients 2024, 16, 18.}, journal = {Nutrients}, volume = {16}, number = {20}, pages = {}, pmid = {39458569}, issn = {2072-6643}, abstract = {Text Correction [...].}, }
@article {pmid39458350, year = {2024}, author = {Marangelo, C and Vernocchi, P and Del Chierico, F and Scanu, M and Marsiglia, R and Petrolo, E and Fucà, E and Guerrera, S and Valeri, G and Vicari, S and Putignani, L}, title = {Stratification of Gut Microbiota Profiling Based on Autism Neuropsychological Assessments.}, journal = {Microorganisms}, volume = {12}, number = {10}, pages = {}, pmid = {39458350}, issn = {2076-2607}, abstract = {Autism spectrum disorder (ASD) is a neurodevelopmental disorder. Investigations of gut microbiota (GM) play an important role in deciphering disease severity and symptoms. Overall, we stratified 70 ASD patients by neuropsychological assessment, based on Calibrated Severity Scores (CSSs) of the Autism Diagnostic Observation Schedule-Second edition (ADOS-2), Child Behavior Checklist (CBCL) and intelligent quotient/developmental quotient (IQ/DQ) parameters. Hence, metataxonomy and PICRUSt-based KEGG predictions of fecal GM were assessed for each clinical subset. Here, 60% of ASD patients showed mild to moderate autism, while the remaining 40% showed severe symptoms; 23% showed no clinical symptoms, 21% had a risk of behavior problems and 56% had clinical symptoms based on the CBCL, which assesses internalizing problems; further, 52% had no clinical symptoms, 21% showed risk, and 26% had clinical symptoms classified by CBCL externalizing problems. Considering the total CBCL index, 34% showed no clinical symptoms, 13% showed risk, and 52% had clinical symptoms. Here, 70% of ASD patients showed cognitive impairment/developmental delay (CI/DD). The GM of ASDs with severe autism was characterized by an increase in Veillonella, a decrease in Monoglobus pectinilyticus and a higher microbial dysbiosis index (MDI) when compared to mild-moderate ASDs. Patients at risk for behavior problems and showing clinical symptoms were characterized by a GM with an increase of Clostridium, Eggerthella, Blautia, Intestinibacter, Coprococcus, Ruminococcus, Onthenecus and Bariatricus, respectively. Peptidoglycan biosynthesis and biofilm formation KEGGs characterized patients with clinical symptoms, while potential microbiota-activated PPAR-γ-signaling was seen in CI/DD patients. This evidence derived from GM profiling may be used to further improve ASD understanding, leasing to a better comprehension of the neurological phenotype.}, }
@article {pmid39458307, year = {2024}, author = {Krause, JL and Engelmann, B and Lallinger, DJD and Rolle-Kampczyk, U and von Bergen, M and Chang, HD}, title = {Multi-Omics Analysis Unravels the Impact of Stool Sample Logistics on Metabolites and Microbial Composition.}, journal = {Microorganisms}, volume = {12}, number = {10}, pages = {}, pmid = {39458307}, issn = {2076-2607}, support = {NNF21OC0066551//Novo Nordisk Foundation/ ; //Dr. Rolf M. Schwiete Stiftung/ ; 375876048//Deutsche Forschungsgemeinschaft/ ; 831434//Innovative Medicines Initiative/ ; }, abstract = {Human health and the human microbiome are inevitably intertwined, increasing their relevance in clinical research. However, the collection, transportation and storage of faecal samples may introduce bias due to methodological differences, especially since postal shipping is a common practise in large-scale clinical cohort studies. Using four different Omics layer, we determined the structural (16S rRNA sequencing, cytometric microbiota profiling) and functional integrity (SCFAs, global metabolome) of the microbiota in relation to different easy-to-handle conditions. These conditions were storage at -20 °C, -20 °C as glycerol stock, 4 °C and room temperature with and without oxygen exposure for a maximum of one week. Storage time affected the microbiota on all Omics levels. However, the magnitude was donor-dependent, highlighting the need for purpose-optimized sample collection in clinical multi-donor studies. The effects of oxygen exposure were negligible for all analyses. At ambient temperature, SCFA and compositional profiles were stable for 24 h and 48 h, respectively, while at 4 °C, SCFA profiles were maintained for 48 h. The global metabolome was highly susceptible, already changing at 24 h in non-frozen conditions. Thus, faecal microbiota was best preserved on all levels when transported as a native sample frozen within 24 h, leading to the least biased outcomes in the analysis. We conclude that the immediate freezing of native stool samples for transportation to the lab is best suited for planned multi-Omics analyses that include metabolomics to extend standard sequencing approaches.}, }
@article {pmid39455951, year = {2024}, author = {Rastegar, S and Skurnik, M and Tadjrobehkar, O and Samareh, A and Samare-Najaf, M and Lotfian, Z and Khajedadian, M and Hosseini-Nave, H and Sabouri, S}, title = {Synergistic effects of bacteriophage cocktail and antibiotics combinations against extensively drug-resistant Acinetobacter baumannii.}, journal = {BMC infectious diseases}, volume = {24}, number = {1}, pages = {1208}, pmid = {39455951}, issn = {1471-2334}, support = {402000840//Hossein Hosseini-Nave/ ; }, mesh = {*Acinetobacter baumannii/virology/drug effects ; *Biofilms/drug effects/growth &amp; development ; *Anti-Bacterial Agents/pharmacology ; *Bacteriophages/physiology ; *Acinetobacter Infections/microbiology/therapy ; Humans ; *Drug Resistance, Multiple, Bacterial ; Phage Therapy/methods ; Microbial Sensitivity Tests ; }, abstract = {BACKGROUND: The extensively drug-resistant (XDR) strains of Acinetobacter baumannii have become a major cause of nosocomial infections, increasing morbidity and mortality worldwide. Many different treatments, including phage therapy, are attractive ways to overcome the challenges of antibiotic resistance.<br><br>METHODS: This study investigates the biofilm formation ability of 30 XDR A. baumannii isolates and the efficacy of a cocktail of four tempetate bacteriophages (SA1, Eve, Ftm, and Gln) and different antibiotics (ampicillin/sulbactam, meropenem, and colistin) in inhibiting and degrading the biofilms of these strains.<br><br>RESULTS: The majority (83.3%) of the strains exhibited strong biofilm formation. The bacteriophage cocktail showed varying degrees of effectiveness against A. baumannii biofilms, with higher concentrations generally leading to more significant inhibition and degradation rates. The antibiotics-bacteriophage cocktail combinations also enhanced the inhibition and degradation of biofilms.<br><br>CONCLUSION: The findings suggested that the bacteriophage cocktail is an effective tool in combating A. baumannii biofilms, with its efficacy depending on the concentration. Combining antibiotics with the bacteriophage cocktail improved the inhibition and removal of biofilms, indicating a promising strategy for managing A. baumannii infections. These results contribute to our understanding of biofilm dynamics and the potential of bacteriophage cocktails as a novel therapeutic approach to combat antibiotic-resistant bacteria.}, }
@article {pmid39452183, year = {2024}, author = {Otava, UE and Tervo, L and Havela, R and Vuotari, L and Ylänne, M and Asplund, A and Patpatia, S and Kiljunen, S}, title = {Phage-Antibiotic Combination Therapy against Recurrent Pseudomonas Septicaemia in a Patient with an Arterial Stent.}, journal = {Antibiotics (Basel, Switzerland)}, volume = {13}, number = {10}, pages = {}, pmid = {39452183}, issn = {2079-6382}, support = {336519//Research Council of Finland/ ; PROFI7//Research Council of Finland/ ; n.a.//Jane and Aatos Erkko Foundation/ ; }, abstract = {Background: Intravascular stent infections are often associated with high risks of morbidity and mortality. We report here a case of a patient with an arterial stent and recurrent Pseudomonas septicaemias successfully treated with phage-meropenem combination therapy. Methods: A 75-year-old female with arteriosclerosis and comorbidities went through a femoropopliteal bypass with prosthesis in the right inguinal area. After the bypass, she developed a recurring Pseudomonas aeruginosa infection and also neutropenia during different antibiotics. A rapidly growing pseudoaneurysm in the right inguinal area led to an emergency intra-arterial stent placement during blood stream infection, later suspected to host a P. aeruginosa biofilm. Removing the stent was deemed precarious, and phage therapy was considered as a compassionate treatment option. A three-phage cocktail infecting the P. aeruginosa strain was prepared and administered intravenously together with meropenem for two weeks, after which, a ten-month follow-up was carried out. Results: No adverse reactions occurred during the phage therapy treatment, while infection markers were normalized. In addition, recovery was seen in a PET-CT scan. During the 10-month follow-up, no further P. aeruginosa septicaemias occurred. Conclusions: Phage-meropenem combination therapy was thus found safe and effective in the treatment of recurrent Pseudomonas septicaemia in a patient with an arterial stent.}, }
@article {pmid39450961, year = {2024}, author = {Sansonetti, PJ and Doré, J}, title = {[The human microbiome proofed by the Anthropocene: from correlation to causality and intervention].}, journal = {Medecine sciences : M/S}, volume = {40}, number = {10}, pages = {757-765}, doi = {10.1051/medsci/2024121}, pmid = {39450961}, issn = {1958-5381}, mesh = {Humans ; *Microbiota/physiology ; Animals ; *Gastrointestinal Microbiome/physiology ; *Dysbiosis/microbiology ; Biodiversity ; Causality ; Climate Change ; }, abstract = {The deleterious effects of human activities on biodiversity in the vegetal and animal world, and on climate changes are now well-established facts. However, little is yet known on the impact of human activities on microbial diversity on the planet and more specifically on the human microbiota Large implementation of metagenomics allows exaustive microbial cataloguing with broad spatio-temporal resolution of human microbiota. A reduction in bacterial richness and diversity in the human microbiota, particularly in the intestinal tract, is now established and particularly obvious in the most industrialized regions of the planet. Massive, uncontrolled use of antibiotics, drastic changes in traditional food habits and some elements of the "global exposome" that remain to identify are usually considered as stressors accounting for this situation of "missing microbes". As a consequence, a dysbiotic situation develops, a "dysbiosis" being characterized by the erosion of the central core of shared bacterial species across individuals and the development of opportunistic "pathobionts" in response to a weaker barrier capacity of these impoverished microbiota. The current challenge is to establish a causality link between the extension of these dysbiotic situations and the steady emergence of epidemic, non-communicable diseases such as asthma, allergy, obesity, diabetes, autoimmune diseases and some cancers. Experimental animal models combined with controlled, prospective clinical interventions are in demand to consolidate causality links, with the understanding that in the deciphering of the mechanisms of alteration of the human-microbiome symbiosis resides a novel exciting chapter of medicine: "microbial medicine".}, }
@article {pmid39447121, year = {2024}, author = {Jia, B and Baek, JH and Lee, JK and Sun, Y and Kim, KH and Jung, JY and Jeon, CO}, title = {Expanding the β-Lactamase Family in the Human Microbiome.}, journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)}, volume = {11}, number = {46}, pages = {e2403563}, pmid = {39447121}, issn = {2198-3844}, support = {2024SSY0104//Pioneer"and"Leading Goose"R&amp;DProgram of Zhejiang/ ; 2023C4S01002//Xianghu Laboratory/ ; 2018R1A5A1025077//Xianghu Laboratory/ ; 2018R1A5A1025077//Ministry of Science and ICT of the Ministry of Science and ICT, Republic of Korea/ ; 2021003420003//Korea Environment Industry &amp; Technology Institute (KEITI) through the Project to make multi-ministerial national biological research resources more advanced, funded by Korea Ministry of Environment (MOE), Republic of Korea/ ; }, mesh = {Humans ; *beta-Lactamases/metabolism/genetics ; Female ; Microbiota/genetics ; Gastrointestinal Microbiome/genetics/physiology/drug effects ; Male ; Adult ; Anti-Bacterial Agents/pharmacology ; beta-Lactams/pharmacology ; Middle Aged ; }, abstract = {β-lactams, the most common antibiotics globally, have resistance primarily determined by β-lactamases. Human microbiota and β-lactams influence mutually; however, β-lactamase variety and abundance in the human microbiome remain partially understood. This study aimed to elucidate the diversity, abundance, and substrate spectrum of β-lactamases. 1369 characterized β-lactamases and 16 204 putative sequences are collected from protein databases. Upon clustering analysis and biochemical assays, nine proteins exhibiting less than 35% identity to those previously characterized are confirmed as β-lactamases. These newly identified β-lactamases originated from eight distinct clusters comprising 1163 β-lactamases. Quantifying healthy participants (n = 2394) across 19 countries using functionally confirmed clusters revealed that Japan have the highest gut β-lactamase abundance (log2[reads per million (RPM)] = 6.52) and Fiji have the lowest (log2[RPM] = 2.31). The β-lactamase abundance is correlated with β-lactam consumption (R = 0.50, p = 0.029) and income (R = 0.51, p = 0.024). Comparing individuals with ailments with healthy participants, β-lactamase abundance in the gut is increased significantly in patients with colorectal cancer, cardiovascular diseases, breast cancer, and epilepsy. These outcomes provide insights into investigating antibiotic resistance, antibiotic stewardship, and gut microbiome-antibiotic interactions.}, }
@article {pmid39443987, year = {2024}, author = {Levi Mortera, S and Marzano, V and Rapisarda, F and Marangelo, C and Pirona, I and Vernocchi, P and Di Michele, M and Del Chierico, F and Quintero, MA and Fernandez, I and Hazime, H and Killian, RM and Solis, N and Ortega, M and Damas, OM and Proksell, S and Kerman, DH and Deshpande, AR and Garces, L and Scaldaferri, F and Gasbarrini, A and Abreu, MT and Putignani, L}, title = {Metaproteomics reveals diet-induced changes in gut microbiome function according to Crohn's disease location.}, journal = {Microbiome}, volume = {12}, number = {1}, pages = {217}, pmid = {39443987}, issn = {2049-2618}, mesh = {Humans ; *Crohn Disease/microbiology ; *Gastrointestinal Microbiome ; Male ; Female ; *Feces/microbiology ; Adult ; *Proteomics ; Middle Aged ; Diet ; Dietary Fiber/administration &amp; dosage ; Bacteria/classification/isolation &amp; purification/genetics ; Colon/microbiology ; Young Adult ; Faecalibacterium/isolation &amp; purification ; }, abstract = {BACKGROUND: Crohn's disease (CD) is characterized by chronic intestinal inflammation. Diet is a key modifiable factor influencing the gut microbiome (GM) and a risk factor for CD. However, the impact of diet modulation on GM function in CD patients is understudied. Herein, we evaluated the effect of a high-fiber, low-fat diet (the Mi-IBD diet) on GM function in CD patients. All participants were instructed to follow the Mi-IBD diet for 8 weeks. One group of CD patients received one-time diet counseling only (Gr1); catered food was supplied for the other three groups, including CD patients (Gr2) and dyads of CD patients and healthy household controls (HHCs) residing within the same household (Gr3-HHC dyads). Stool samples were collected at baseline, week 8, and week 36, and analyzed by liquid chromatography-tandem mass spectrometry.<br><br>RESULTS: At baseline, the metaproteomic profiles of CD patients and HHCs differed. The Mi-IBD diet significantly increased carbohydrate and iron transport and metabolism. The predicted microbial composition underlying the metaproteomic changes differed between patients with ileal only disease (ICD) or colonic involvement: ICD was characterized by decreased Faecalibacterium abundance. Even on the Mi-IBD diet, the CD patient metaproteome displayed significant underrepresentation of carbohydrate and purine/pyrimidine synthesis pathways compared to that of HHCs. Human immune-related proteins were upregulated in CD patients compared to HHCs.<br><br>CONCLUSIONS: The Mi-IBD diet changed the microbial function of CD patients and enhanced carbohydrate metabolism. Our metaproteomic results highlight functional differences in the microbiome according to disease location. Notably, our dietary intervention yielded the most benefit for CD patients with colonic involvement compared to ileal-only disease. Video Abstract.}, }
@article {pmid39443812, year = {2024}, author = {Joos, R and Boucher, K and Lavelle, A and Arumugam, M and Blaser, MJ and Claesson, MJ and Clarke, G and Cotter, PD and De Sordi, L and Dominguez-Bello, MG and Dutilh, BE and Ehrlich, SD and Ghosh, TS and Hill, C and Junot, C and Lahti, L and Lawley, TD and Licht, TR and Maguin, E and Makhalanyane, TP and Marchesi, JR and Matthijnssens, J and Raes, J and Ravel, J and Salonen, A and Scanlan, PD and Shkoporov, A and Stanton, C and Thiele, I and Tolstoy, I and Walter, J and Yang, B and Yutin, N and Zhernakova, A and Zwart, H and ,  and Doré, J and Ross, RP}, title = {Examining the healthy human microbiome concept.}, journal = {Nature reviews. Microbiology}, volume = {}, number = {}, pages = {}, pmid = {39443812}, issn = {1740-1534}, support = {P30 ES005022/ES/NIEHS NIH HHS/United States ; }, abstract = {Human microbiomes are essential to health throughout the lifespan and are increasingly recognized and studied for their roles in metabolic, immunological and neurological processes. Although the full complexity of these microbial communities is not fully understood, their clinical and industrial exploitation is well advanced and expanding, needing greater oversight guided by a consensus from the research community. One of the most controversial issues in microbiome research is the definition of a 'healthy' human microbiome. This concept is complicated by the microbial variability over different spatial and temporal scales along with the challenge of applying a unified definition to the spectrum of healthy microbiome configurations. In this Perspective, we examine the progress made and the key gaps that remain to be addressed to fully harness the benefits of the human microbiome. We propose a road map to expand our knowledge of the microbiome-health relationship, incorporating epidemiological approaches informed by the unique ecological characteristics of these communities.}, }
@article {pmid39440978, year = {2024}, author = {Soto Ocaña, J and Friedman, ES and Keenan, O and Bayard, NU and Ford, E and Tanes, C and Munneke, MJ and Beavers, WN and Skaar, EP and Bittinger, K and Zemel, BS and Wu, GD and Zackular, JP}, title = {Metal availability shapes early life microbial ecology and community succession.}, journal = {mBio}, volume = {15}, number = {11}, pages = {e0153424}, pmid = {39440978}, issn = {2150-7511}, support = {P30 DK050306/DK/NIDDK NIH HHS/United States ; R01DK107565, P30DK050306//HHS | National Institutes of Health (NIH)/ ; R35GM138369//HHS | NIH | National Institute of General Medical Sciences (NIGMS)/ ; UL1 TR001878/TR/NCATS NIH HHS/United States ; R01DK107565//HHS | National Institutes of Health (NIH)/ ; R01 DK107565/DK/NIDDK NIH HHS/United States ; R35 GM138369/GM/NIGMS NIH HHS/United States ; }, mesh = {Humans ; *Gastrointestinal Microbiome ; Infant ; *Metals/metabolism ; *Leukocyte L1 Antigen Complex/metabolism/analysis ; Bacteria/metabolism/classification/genetics ; Breast Feeding ; Feces/microbiology ; Gastrointestinal Tract/microbiology ; Infant, Newborn ; Microbiota ; Infant Formula ; }, abstract = {The gut microbiota plays a critical role in human health and disease. Microbial community assembly and succession early in life are influenced by numerous factors. In turn, assembly of this microbial community is known to influence the host, including immune system development, and has been linked to outcomes later in life. To date, the role of host-mediated nutritional immunity and metal availability in shaping microbial community assembly and succession early in life has not been explored in depth. Using a human infant cohort, we show that the metal-chelating protein calprotectin is highly abundant in infants. Taxa previously shown to be successful early colonizers of the infant gut, such as Enterococcus, Enterobacteriaceae, and Bacteroides, are highly resistant to experimental metal starvation in culture. Lactobacillus, meanwhile, is highly susceptible to metal restriction, pointing to a possible mechanism by which host-mediated metal limitation shapes the fitness of early colonizing taxa in the infant gut. We further demonstrate that formula-fed infants harbor markedly higher levels of metals in their gastrointestinal tract compared to breastfed infants. Formula-fed infants with high levels of metals harbor distinct microbial communities compared to breastfed infants, with higher levels of Enterococcus, Enterobacter, and Klebsiella, taxa which show increased resistance to the toxic effects of high metal concentrations. These data highlight a new paradigm in microbial community assembly and suggest an unappreciated role for nutritional immunity and dietary metals in shaping the earliest colonization events of the microbiota.IMPORTANCEEarly life represents a critical window for microbial colonization of the human gastrointestinal tract. Surprisingly, we still know little about the rules that govern the successful colonization of infants and the factors that shape the success of early life microbial colonizers. In this study, we report that metal availability is an important factor in the assembly and succession of the early life microbiota. We show that the host-derived metal-chelating protein, calprotectin, is highly abundant in infants and successful early life colonizers can overcome metal restriction. We further demonstrate that feeding modality (breastmilk vs formula) markedly impacts metal levels in the gut, potentially influencing microbial community succession. Our work suggests that metals, a previously unexplored aspect of early life ecology, may play a critical role in shaping the early events of microbiota assembly in infants.}, }
@article {pmid39439268, year = {2024}, author = {Weinkove, D}, title = {Folates, bacteria and ageing: insights from the model organism C. elegans in the study of nutrition and ageing.}, journal = {The Proceedings of the Nutrition Society}, volume = {}, number = {}, pages = {1-5}, pmid = {39439268}, issn = {1475-2719}, support = {BB/H01974X/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; }, abstract = {The relationship between nutrition and ageing is complex. The metabolism and synthesis of micronutrients within the gut microbiome can influence human health but is challenging to study. Furthermore, studying ageing in humans is time-consuming and difficult to control for environmental factors. Studies in model organisms can guide research efforts in this area. This review describes how the nematode Caenorhabditis elegans can be used to study how bacteria and diet influence ageing and inform follow-on studies in humans. It is known that certain bacteria accelerate ageing in C. elegans. This age-accelerating effect is prevented by inhibiting folate synthesis within the bacteria, and we propose that in the human microbiome, certain bacteria also accelerate ageing in a way that can be modulated by interfering with bacterial folate synthesis. Bacterial-derived folates do not promote ageing themselves; rather, ageing is accelerated by bacteria in some way, either through secondary metabolites or other bacterial activity, which is dependent on bacterial folate synthesis. In humans, it may be possible to inhibit bacterial folate synthesis in the human gut while maintaining healthy folate status in the body via food and supplementation. The supplement form of folic acid has a common breakdown product that can be used by bacteria to increase folate synthesis. Thus, supplementation with folic acid may not be good for health in certain circumstances such as in older people or those with an excess of proteobacteria in their microbiome. For these groups, alternative supplement strategies may be a safer way to ensure adequate folate levels.}, }
@article {pmid39435653, year = {2024}, author = {Rastegar, S and Sabouri, S and Tadjrobehkar, O and Samareh, A and Niaz, H and Sanjari, N and Hosseini-Nave, H and Skurnik, M}, title = {Characterization of bacteriophage vB_AbaS_SA1 and its synergistic effects with antibiotics against clinical multidrug-resistant Acinetobacter baumannii isolates.}, journal = {Pathogens and disease}, volume = {82}, number = {}, pages = {}, pmid = {39435653}, issn = {2049-632X}, support = {//University of Helsinki/ ; KMU.AC.IR.400000652//Kerman University of Medical Sciences/ ; }, mesh = {*Acinetobacter baumannii/virology/drug effects ; *Anti-Bacterial Agents/pharmacology ; *Drug Resistance, Multiple, Bacterial ; *Bacteriophages/genetics/isolation &amp; purification/physiology/classification ; *Acinetobacter Infections/microbiology ; Humans ; *Genome, Viral ; *Host Specificity ; Microbial Sensitivity Tests ; Sewage/virology/microbiology ; Phage Therapy ; DNA, Viral/genetics ; Viral Plaque Assay ; }, abstract = {Acinetobacter baumannii is a major cause of nosocomial infections globally. The increasing prevalence of multidrug-resistant (MDR) A. baumannii has become an important public health concern. To combat drug resistance, alternative methods such as phage therapy have been suggested. In total, 30 MDR A. baumannii strains were isolated from clinical specimens, and their antibiotic susceptibilities were determined. The Acinetobacter phage vB_AbaS_SA1, isolated from hospital sewage, was characterized. In addition to its plaque size, particle morphology, and host range, its genome sequence was determined and annotated. Finally, the antibacterial effects of phage alone, antibiotics alone, and phage/antibiotic combinations were assessed against the A. baumannii strains. Phage vB_AbaS_SA1 had siphovirus morphology, showed a latent period of 20 min, and a 250 PFU/cell (plaque forming unit/cell) burst size. When combined with antibiotics, vB_AbaS_SA1 (SA1) showed a significant phage-antibiotic synergy effect and reduced the overall effective concentration of antibiotics in time-kill assessments. The genome of SA1 is a linear double-stranded DNA of 50 108 bp in size with a guanine-cytosine (GC) content of 39.15%. Despite the potent antibacterial effect of SA1, it is necessary to perform additional research to completely elucidate the mechanisms of action and potential constraints associated with utilizing this bacteriophage.}, }
@article {pmid39429878, year = {2024}, author = {Chen, J and Luo, J and Pouwels, S and Li, B and Wu, B and Abdelbaki, TN and Arcot, J and Yang, W}, title = {Dietary therapies interlinking with gut microbes toward human health: Past, present, and future.}, journal = {iMeta}, volume = {3}, number = {5}, pages = {e230}, pmid = {39429878}, issn = {2770-596X}, abstract = {Overview of personalized dietary therapies. This flow chart exhibits the future prospect for integrating human microbiome and bio-medical research to revolutionize the precise personalized dietary therapies. With the development of artificial intelligence (AI), incorporating database may achieve personalized dietary therapies with high precision.}, }
@article {pmid39425798, year = {2024}, author = {Goladze, S and Patpatia, S and Tuomala, H and Ylänne, M and Gachechiladze, N and de Oliveira Patricio, D and Skurnik, M and Sundberg, LR}, title = {Isolation and characterization of Yersinia phage fMtkYen3-01.}, journal = {Archives of virology}, volume = {169}, number = {11}, pages = {226}, pmid = {39425798}, issn = {1432-8798}, support = {PHDF-21-2176//Shota Rustaveli National Science Foundation/ ; #346772//Research Council of Finland/ ; }, mesh = {*Yersinia enterocolitica/virology/genetics ; *Genome, Viral/genetics ; *Bacteriophages/genetics/classification/isolation &amp; purification/physiology ; Yersinia Infections/microbiology/therapy/virology ; Base Composition ; Humans ; Phage Therapy/methods ; }, abstract = {Yersinia enterocolitica causes yersiniosis, the third most common gastrointestinal infection in humans throughout Europe. The emergence of multidrug resistance and the lack of effective new antibiotics have drawn attention to phage therapy as a treatment option. Here, we report the complete genome sequence of phage fMtkYen3-01, which infects Y. enterocolitica serotype O:3 strains. This phage has a genome 40,415 bp in length with 45.1% GC content and 49 predicted genes. fMtkYen3-01 infected 9.5% of the 42 Y. enterocolitica strains tested and showed stability at 25-40 °C, as well as pH 5.0-10.0. These results suggest the therapeutic potential of this phage.}, }
@article {pmid39421627, year = {2024}, author = {Beschastnov, VV and Shirokova, IY and Belyanina, NA and Pogodin, IE and Tulupov, AA and Tochilina, AG and Belova, IV and Tyumenkov, YO and Kovalishena, OV and Soloveva, IV}, title = {Evaluation of the Feasibility of Using Commercial Wound Coatings as a Carrier Matrix for Bacteriophages.}, journal = {Sovremennye tekhnologii v meditsine}, volume = {16}, number = {1}, pages = {45-52}, pmid = {39421627}, issn = {2309-995X}, mesh = {Humans ; *Bacteriophages ; *Wound Infection/therapy ; Staphylococcus aureus/virology/drug effects ; Wound Healing ; Phage Therapy ; Bandages ; Feasibility Studies ; }, abstract = {UNLABELLED: The aim of the investigation is to study the possibility of applying commercial wound coatings for treating infected wounds as a carrier matrix for bacteriophages.<br><br>MATERIALS AND METHODS: Twelve varieties of commercial wound coverings based on biopolymers of natural and synthetic origin, a biological preparation Staphylophag produced by scientific-industrial association Microgen (Russia), registration certificate P N001973/01, and the S. aureus 3196 test strain (GenBank JARQZO000000000) isolated from a patient with a burn wound have been used in our work. The ability of commercial biological wound coatings to absorb solutions was examined by immersing them in a physiological solution (pH 7.0-7.2) followed by weighing. The lytic activity of three bacteriophage series against the test strain was studied using the Appelman method and a spot test. The lytic activity of the bacteriophage in the wound samples was studied within 7 days after its absorption by the wound coatings.<br><br>RESULTS: The greatest volume of fluid was absorbed by the LycoSorb, NEOFIX FibroSorb Ag, Biatravm, and Chitocol-S wound coatings. All bacteriophage series have been found to have a high lytic activity against the test strain. It has also been shown that Chitocol-S, Collachit-FA, Algipran, and Aquacel Ag Extra possessed their own inherent antibacterial activity under in vitro conditions stable for 7 days; moreover, the lysis zones of the test strain increased after their saturation with bacteriophage. On day 0, a high level of bacteriophage lytic activity with the maximum size of the test strain lysis zones from 49 to 59 mm have been found to remain in all samples of the wound coverings. The bacteriophage activity persisted for 1 day in the samples of Hydrofilm, Polypran, and NEOFIX FibroCold Ag coatings, up to 4 days in Algipran, Nano-Aseptica, and Biatravm coatings; and for 7 days in the Chitocol-S, Collachit-FA, Opsite Post-Op Visible, NEOFIX FibroSorb Ag, Aquacel Ag Extra, and LycoSorb samples.<br><br>CONCLUSION: Modern commercial wound dressings based on chitosan-collagen complex (Chitocol-S, Collachit-FA), polyurethane (Opsite Post-Op Visible, LycoSorb, NEOFIX FibroSorb Ag), and Hydrofiber (Aquacel Ag Extra) have a sufficient level of bacteriophage solution absorption, provide a stable preservation of the bacteriophage lytic activity under in vitro conditions up to 7 days. Thus, the in vitro studies prove the possibility of their use as a carrier matrix for bacteriophages.}, }
@article {pmid39421255, year = {2024}, author = {Geerlings, SY and van der Ark, K and Nijsse, B and Boeren, S and van Loosdrecht, M and Belzer, C and de Vos, WM}, title = {Omics-based analysis of Akkermansia muciniphila cultivation in food-grade media.}, journal = {Microbiome research reports}, volume = {3}, number = {3}, pages = {36}, pmid = {39421255}, issn = {2771-5965}, abstract = {Background and Aim: Over the past years, the gut microbiota and its correlation to health and disease has been studied extensively. In terms of beneficial microbes, an increased interest in Akkermansia muciniphila (A. muciniphila) has been observed since its discovery. Direct evidence for the role of A. muciniphila in host health has been provided in both mice and human studies. However, for human interventions with A. muciniphila cells, industrial-scale fermentations are needed, and hence, the used cultivation media should be free of animal-derived components, food-grade, non-allergenic and allow for efficient growth to high densities to provide cost-effective production platforms. In this study, we assessed the growth and performance of A. muciniphila in batch bioreactors using newly developed plant-based media. Methods: The bioreactors were supplemented with varying carbon sources, including different ratios of N-acetylglucosamine (GlcNAc) and glucose. We monitored the growth of A. muciniphila in the plant-based medium using optical density (OD600) measurements and microscopy. In addition, we used a combination of biochemical analysis as well as transcriptional and proteomics analysis to gain detailed insight into the physiology. Results: Comparisons between growth on these media and that on mucin revealed differences at both transcriptome and proteome levels, including differences in the expression of glycosyltransferases, signaling proteins, and stress response. Furthermore, elongated cells and higher OD600 values were observed using the plant-based media as compared to cultivation media containing mucin. Conclusion: These differences do not hamper growth, and therefore, our data suggest that the food-grade medium composition described here could be used to produce A. muciniphila with high yields for therapeutic purposes.}, }
@article {pmid39421250, year = {2024}, author = {Puhlmann, ML and van de Rakt, E and Kerezoudi, EN and Rangel, I and Brummer, RJ and Smidt, H and Kaper, FS and de Vos, WM}, title = {Analysis of the fermentation kinetics and gut microbiota modulatory effect of dried chicory root reveals the impact of the plant-cell matrix rationalizing its conversion in the distal colon.}, journal = {Microbiome research reports}, volume = {3}, number = {3}, pages = {28}, pmid = {39421250}, issn = {2771-5965}, abstract = {Aim: The cell matrix of plant foods has received little attention in prebiotic fiber research. We aimed to understand the impact of the plant cell matrix in dried chicory root on its breakdown in the human gut to explain its reported beneficial effects on gut and metabolic health. Methods: We applied in vitro digestion and fermentation models together with an ex vivo gut barrier integrity model. Plant cell matrix intactness in the upper gastrointestinal tract was investigated by scanning electron microscopy. Colonic breakdown of inulin, and chicory root cubes and powder was assessed by gut microbiota analysis using 16S rRNA gene amplicon sequencing and determining the kinetics of changes in pH, gas, and short-chain fatty acid (SCFA) production. Finally, effects on gut barrier integrity were explored by exposing colonic biopsies to fermentation supernatants in an Ussing chamber model. Results: The plant cell matrix of dried chicory root cubes remained intact throughout upper gastrointestinal transit. Dried chicory root fermentation resulted in higher final relative abundances of pectin-degrading Monoglobus and butyrate-producing Roseburia spp. compared to inulin and a seven-fold increase in Bifidobacterium spp. in donors where these species were present. Dried chicory root cubes yielded similar total SCFAs but higher final butyrate levels than chicory root powder or isolated inulin with less gas produced. No uniform but donor-specific effects of fermentation supernatants on the maintenance of gut barrier integrity were detected. Conclusion: The intact plant cell matrix of dried chicory root affected its colonic breakdown kinetics and microbiota, underpinning its beneficial effect in vivo.}, }
@article {pmid39419193, year = {2024}, author = {Chen, H and Zeng, M and Batool, SS and Zhao, Y and Yu, Z and Zhou, J and Liu, K and Huang, J}, title = {Metagenomic analysis reveals effects of gut microbiome in response to neoadjuvant chemoradiotherapy in advanced rectal cancer.}, journal = {Genomics}, volume = {116}, number = {6}, pages = {110951}, doi = {10.1016/j.ygeno.2024.110951}, pmid = {39419193}, issn = {1089-8646}, mesh = {Humans ; *Rectal Neoplasms/therapy/microbiology/genetics/metabolism ; *Gastrointestinal Microbiome ; *Neoadjuvant Therapy ; Chemoradiotherapy ; Female ; Male ; Middle Aged ; Metagenomics ; Aged ; Metagenome ; Feces/microbiology ; Bacteria/genetics/classification/metabolism ; }, abstract = {Neoadjuvant chemoradiotherapy can enhance survival rate of patients with advanced rectal cancer, but its effectiveness varies considerably. Previous studies have indicated that gut microbes may serve as biomarkers for predicting treatment efficacy. However, the specific roles of the gut microbiome in patients who have good response to nCRT remains unclear. In this study, shotgun metagenomic sequencing technology was used to analyze the fecal microbiome of patients with varying responses to nCRT. Our findings revealed that beneficial intestinal bacteria and genes from different metabolic pathways (carbohydrate metabolism, amino acid metabolism, and sulfur metabolism) were significantly enriched in patients with good response. Additionally, causal relationship in which microbial-derived GDP-D-rhamnose and butyrate could influence the response to nCRT was clarified. Our results offered new insights into the different response to nCRT, and provided valuable reference points for improving the effectiveness of nCRT in patients with advanced colorectal cancer.}, }
@article {pmid39415150, year = {2024}, author = {Ma, J and Wang, F and Zhu, Y and Tian, Y and Du, C and Yan, L and Ding, C and Wang, D}, title = {Oral microbiome dysbiosis may be associated with intra cranial aneurysms.}, journal = {BMC oral health}, volume = {24}, number = {1}, pages = {1235}, pmid = {39415150}, issn = {1472-6831}, support = {2021J01217//Fujian Provincial Nature Foundation/ ; 2021Y2001//Technology Platform Construction Project of Fujian Province/ ; }, mesh = {Humans ; *Intracranial Aneurysm/microbiology ; Female ; Male ; Middle Aged ; *Dysbiosis/microbiology ; *Microbiota ; Case-Control Studies ; *Saliva/microbiology ; Mouth/microbiology ; RNA, Ribosomal, 16S/analysis ; Adult ; Aged ; High-Throughput Nucleotide Sequencing ; }, abstract = {BACKGROUND: Although the etiology of aneurysms remains elusive, recent advances in high-throughput sequencing technology and ongoing human microbiome investigations suggest a potential link between microbiome composition and the onset of various human diseases.<br><br>OBJECTIVE: This study aimed to utilize high-throughput 16&#xa0;S rRNA gene sequencing to analyze the oral flora bacterial profiles of individuals, comparing patients with intracranial aneurysms to a healthy control group. Importantly, we sought to identify differences in the oral microbiota and offer novel insights and methods for early diagnosis and identification of intracranial aneurysms.<br><br>METHOD: Saliva samples were collected from 60 patients with cerebral aneurysms (case group) and 130 healthy individuals (control group). The V3-V4 region of the bacterial 16&#xa0;S rRNA gene was amplified and sequenced using the HiSeq high-throughput sequencing platform to establish the bacterial profile. Sequencing data were analyzed using QIIME2 and Metastats software to compare composition differences and relative abundance at the phylum and genus levels in the oral microbiota of the two groups.<br><br>RESULTS: Significant differences in oral microbiota composition were observed between patients in the case and control groups (P&#x2009;<&#x2009;0.05). Genus-level identification highlighted key positions occupied by Eubacterium, Saccharimonadaceae, Rothia, Gemella, Streptococcus, Lactobacillales, Phocaeicola, Bacteroides, Saccharimonadales, and Abiotrophia.<br><br>CONCLUSION: This study revealed noteworthy distinctions in the composition, abundance, and diversity of oral microbiota between intracranial aneurysm patients and healthy controls. These disparities suggest a potential correlation between oral microbiota and the development of intracranial aneurysms, offering new avenues for early diagnosis and intervention. However, limitations such as a small sample size, lack of prospective design, and absence of causal inference warrant further validation and exploration.}, }
@article {pmid39408199, year = {2024}, author = {Iannotti, L and Rueda García, AM and Palma, G and Fontaine, F and Scherf, B and Neufeld, LM and Zimmerman, R and Fracassi, P}, title = {Terrestrial Animal Source Foods and Health Outcomes for Those with Special Nutrient Needs in the Life Course.}, journal = {Nutrients}, volume = {16}, number = {19}, pages = {}, pmid = {39408199}, issn = {2072-6643}, mesh = {Adult ; Animals ; Child ; Female ; Humans ; Pregnancy ; *Dairy Products ; *Diet ; *Eggs ; Food Hypersensitivity/epidemiology/prevention &amp; control ; *Meat ; Milk ; Nutrients/analysis ; }, abstract = {Background. Animal source foods are under scrutiny for their role in human health, yet some nutritionally vulnerable populations are largely absent from consideration. Methods. Applying a Population Intervention/Exposure Comparator Outcome (PICO/PECO) framework and prioritizing systematic review and meta-analyses, we reviewed the literature on terrestrial animal source foods (TASFs) and human health, by life course phase. Results. There were consistent findings for milk and dairy products on positive health outcomes during pregnancy and lactation, childhood, and among older adults. Eggs were found to promote early childhood growth, depending on context. Unprocessed meat consumption was associated with a reduced risk for anemia during pregnancy, improved cognition among school-age children, and muscle health in older adults. Milk and eggs represent a risk for food sensitivities/allergies, though prevalence is low, and individuals tend to outgrow the allergies. TASFs affect the human microbiome and associated metabolites with both positive and negative health repercussions, varying by type and quantity. Conclusions. There were substantial gaps in the evidence base for studies limiting our review, specifically for studies in populations outside high-income countries and for several TASF types (pig, poultry, less common livestock species, wild animals, and insects). Nonetheless, sufficient evidence supports an important role for TASFs in health during certain periods of the life course.}, }
@article {pmid39406893, year = {2024}, author = {Ioannou, A and Berkhout, MD and Geerlings, SY and Belzer, C}, title = {Akkermansia muciniphila: biology, microbial ecology, host interactions and therapeutic potential.}, journal = {Nature reviews. Microbiology}, volume = {}, number = {}, pages = {}, pmid = {39406893}, issn = {1740-1534}, abstract = {Akkermansia muciniphila is a gut bacterium that colonizes the gut mucosa, has a role in maintaining gut health and shows promise for potential therapeutic applications. The discovery of A. muciniphila as an important member of our gut microbiome, occupying an extraordinary niche in the human gut, has led to new hypotheses on gut health, beneficial microorganisms and host-microbiota interactions. This microorganism has established a unique position in human microbiome research, similar to its role in the gut ecosystem. Its unique traits in using mucin sugars and mechanisms of action that can modify host health have made A. muciniphila a subject of enormous attention from multiple research fields. A. muciniphila is becoming a model organism studied for its ability to modulate human health and gut microbiome structure, leading to commercial products, a genetic model and possible probiotic formulations. This Review provides an overview of A. muciniphila and Akkermansia genus phylogeny, ecophysiology and diversity. Furthermore, the Review discusses perspectives on ecology, strategies for harnessing beneficial effects of A. muciniphila for human mucosal metabolic and gut health, and its potential as a biomarker for diagnostics and prognostics.}, }
@article {pmid39403892, year = {2024}, author = {Wang, B and Shen, Y and Fang, J and Su, X and Xu, ZZ}, title = {DeepPhylo: Phylogeny-Aware Microbial Embeddings Enhanced Predictive Accuracy in Human Microbiome Data Analysis.}, journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)}, volume = {11}, number = {45}, pages = {e2404277}, pmid = {39403892}, issn = {2198-3844}, support = {2022YFA1304200//National Key RD Program of China/ ; }, mesh = {Humans ; *Microbiota/genetics ; *Phylogeny ; Data Analysis ; Inflammatory Bowel Diseases/microbiology ; Female ; Male ; }, abstract = {Microbial data analysis poses significant challenges due to its high dimensionality, sparsity, and compositionality. Recent advances have shown that integrating abundance and phylogenetic information is an effective strategy for uncovering robust patterns and enhancing the predictive performance in microbiome studies. However, existing methods primarily focus on the hierarchical structure of phylogenetic trees, overlooking the evolutionary distances embedded within them. This study introduces DeepPhylo, a novel method that employs phylogeny-aware amplicon embeddings to effectively integrate abundance and phylogenetic information. DeepPhylo improves both the unsupervised discriminatory power and supervised predictive accuracy of microbiome data analysis. Compared to the existing methods, DeepPhylo demonstrates superiority in informing biologically relevant insights across five real-world microbiome use cases, including clustering of skin microbiomes, prediction of host chronological age and gender, diagnosis of inflammatory bowel disease (IBD) across 15 studies, and multilabel disease classification.}, }
@article {pmid39401296, year = {2024}, author = {Wang, S and Ilves, M and Mäenpää, K and Zhao, L and El-Nezami, H and Karisola, P and Alenius, H}, title = {ZnO Nanoparticles as Potent Inducers of Dermal Immunosuppression in Contact Hypersensitivity in Mice.}, journal = {ACS nano}, volume = {18}, number = {43}, pages = {29479-29491}, pmid = {39401296}, issn = {1936-086X}, mesh = {Animals ; *Zinc Oxide/chemistry/pharmacology ; Mice ; *Dermatitis, Contact/immunology/pathology ; Humans ; Female ; Skin/drug effects/immunology/pathology ; Nanoparticles/chemistry ; Oxazolone ; Mice, Inbred BALB C ; THP-1 Cells ; Disease Models, Animal ; Metal Nanoparticles/chemistry ; }, abstract = {Nanosized zinc oxide (nZnO) metal particles are used in skin creams and sunscreens to enhance their texture and optical properties as UV filters. Despite their common use, little is known about the molecular mechanisms of nZnO exposure on damaged skin. We studied the effects of topically applied nZnO particles on allergic skin inflammation in an oxazolone (OXA)-induced contact hypersensitivity (CHS) mouse model. We investigated whether exposure to nZnO during the sensitization or challenge phase would induce immunological changes and modulate transcriptional responses. We followed skin thickness, cellular infiltration, and changes in the local transcriptome up to 28 days after the challenge. The responses peaked at 24 h and were fully resolved by 28 days. Co-exposure to nZnO and hapten did not interfere with the formation of the sensitization process. Conversely, during the hapten challenge, the application of nZnO fully suppressed the development of the CHS response by the inhibition of pro-inflammatory pathways, secretion of pro-inflammatory cytokines, and proliferation of immune cells. In differentiated and stimulated THP-1 cells and the CHS mouse model, we found that nZnO particles and Zn ions contributed to anti-inflammatory responses. The immunosuppressive properties of nZnO in inflamed skin are mediated by impaired IL-1R-, CXCR2-, and LTB4-mediated pathways. nZnO-induced dermal immunosuppression may be beneficial for individuals with contact allergies who use nZnO-containing cosmetic products. Our findings also provide a deeper understanding of the mechanisms of nZnO, which could be considered when developing nanoparticle-containing skin products.}, }
@article {pmid39396734, year = {2025}, author = {Kajova, M and Khawaja, T and Kainulainen, K and Kantele, A}, title = {Carbapenemase-producing Enterobacterales emerging in Finland's capital region over 2010-2023: increasing proportion of CPE cases first detected in clinical samples.}, journal = {Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases}, volume = {31}, number = {2}, pages = {296-297}, doi = {10.1016/j.cmi.2024.10.005}, pmid = {39396734}, issn = {1469-0691}, }
@article {pmid39387683, year = {2024}, author = {Li, Z and Wang, Q and Huang, X and Wu, Y and Shan, D}, title = {Microbiome's role in musculoskeletal health through the gut-bone axis insights.}, journal = {Gut microbes}, volume = {16}, number = {1}, pages = {2410478}, pmid = {39387683}, issn = {1949-0984}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Bone and Bones/microbiology ; *Musculoskeletal Diseases/microbiology/physiopathology ; Animals ; Osteoarthritis/microbiology/therapy ; Osteoporosis/microbiology ; Bone Density ; Musculoskeletal System/microbiology ; }, abstract = {The interplay between the human microbiome and the musculoskeletal system represents a burgeoning field of research with profound implications for understanding and treating musculoskeletal disorders. This review articulates the pivotal role of the microbiome in modulating bone health, highlighting the gut-bone axis as a critical nexus for potential therapeutic intervention. Through a meticulous analysis of recent clinical research, we underscore the microbiome's influence on osteoporosis, sarcopenia, osteoarthritis, and rheumatoid arthritis, delineating both the direct and indirect mechanisms by which microbiota could impact musculoskeletal integrity and function. Our investigation reveals novel insights into the microbiota's contribution to bone density regulation, hormone production, immune modulation, and nutrient absorption, laying the groundwork for innovative microbiome-based strategies in musculoskeletal disease management. Significantly, we identify the challenges hindering the translation of research into clinical practice, including the limitations of current microbial sequencing techniques and the need for standardized methodologies in microbiome studies. Furthermore, we highlight promising directions for future research, particularly in the realm of personalized medicine, where the microbiome's variability offers unique opportunities for tailored treatment approaches. This review sets a new agenda for leveraging gut microbiota in the diagnosis, prevention, and treatment of musculoskeletal conditions, marking a pivotal step toward integrating microbiome science into clinical musculoskeletal care.}, }
@article {pmid39394961, year = {2024}, author = {Branck, T and Hu, Z and Nickols, WA and Walsh, AM and Bhosle, A and Short, MI and Nearing, JT and Asnicar, F and McIver, LJ and Maharjan, S and Rahnavard, A and Louyakis, AS and Badri, DV and Brockel, C and Thompson, KN and Huttenhower, C}, title = {Comprehensive profile of the companion animal gut microbiome integrating reference-based and reference-free methods.}, journal = {The ISME journal}, volume = {18}, number = {1}, pages = {}, pmid = {39394961}, issn = {1751-7370}, mesh = {Animals ; *Gastrointestinal Microbiome/genetics ; Dogs/microbiology ; Cats ; *Pets/microbiology ; *Feces/microbiology ; *Phylogeny ; *Metagenome ; Humans ; *Metagenomics ; Bacteria/genetics/classification/isolation &amp; purification ; }, abstract = {The gut microbiome of companion animals is relatively underexplored, despite its relevance to animal health, pet owner health, and basic microbial community biology. Here, we provide the most comprehensive analysis of the canine and feline gut microbiomes to date, incorporating 2639 stool shotgun metagenomes (2272 dog and 367 cat) spanning 14 publicly available datasets (n = 730) and 8 new study populations (n = 1909). These are compared with 238 and 112 baseline human gut metagenomes from the Human Microbiome Project 1-II and a traditionally living Malagasy cohort, respectively, processed in a manner identical to the animal metagenomes. All microbiomes were characterized using reference-based taxonomic and functional profiling, as well as de novo assembly yielding metagenomic assembled genomes clustered into species-level genome bins. Companion animals shared 184 species-level genome bins not found in humans, whereas 198 were found in all three hosts. We applied novel methodology to distinguish strains of these shared organisms either transferred or unique to host species, with phylogenetic patterns suggesting host-specific adaptation of microbial lineages. This corresponded with functional divergence of these lineages by host (e.g. differences in metabolic and antibiotic resistance genes) likely important to companion animal health. This study provides the largest resource to date of companion animal gut metagenomes and greatly contributes to our understanding of the "One Health" concept of a shared microbial environment among humans and companion animals, affecting infectious diseases, immune response, and specific genetic elements.}, }
@article {pmid39392836, year = {2024}, author = {Daisley, BA and Allen-Vercoe, E}, title = {Microbes as medicine.}, journal = {Annals of the New York Academy of Sciences}, volume = {1541}, number = {1}, pages = {63-82}, pmid = {39392836}, issn = {1749-6632}, support = {950-232131//Canada Research Chairs/ ; PDF-402947//Natural Sciences and Engineering Research Council of Canada/ ; //Natural Sciences and Engineering Research Council of Canada/ ; 2023//Natural Sciences and Engineering Research Council of Canada/ ; }, mesh = {Humans ; *Probiotics/therapeutic use ; *Microbiota/drug effects/physiology ; Anti-Bacterial Agents/therapeutic use/pharmacology ; Precision Medicine/methods ; Animals ; }, abstract = {Over the last two decades, advancements in sequencing technologies have significantly deepened our understanding of the human microbiome's complexity, leading to increased concerns about the detrimental effects of antibiotics on these intricate microbial ecosystems. Concurrently, the rise in antimicrobial resistance has intensified the focus on how beneficial microbes can be harnessed to treat diseases and improve health and offer potentially promising alternatives to traditional antibiotic treatments. Here, we provide a comprehensive overview of both established and emerging microbe-centric therapies, from probiotics to advanced microbial ecosystem therapeutics, examine the sophisticated ways in which microbes are used medicinally, and consider their impacts on microbiome homeostasis and health outcomes through a microbial ecology lens. In addition, we explore the concept of rewilding the human microbiome by reintroducing "missing microbes" from nonindustrialized societies and personalizing microbiome modulation to fit individual microbial profiles-highlighting several promising directions for future research. Ultimately, the advancements in sequencing technologies combined with innovative microbial therapies and personalized approaches herald a new era in medicine poised to address antibiotic resistance and improve health outcomes through targeted microbiome management.}, }
@article {pmid39386965, year = {2024}, author = {Muhi, S and Marshall, JL and O'Brien, DP and Johnson, PDR and Ross, G and Ramakrishnan, A and Mackay, LK and Doerflinger, M and McCarthy, JS and Jamrozik, E and Osowicki, J and Stinear, TP}, title = {A human model of Buruli ulcer: Provisional protocol for a Mycobacterium ulcerans controlled human infection study.}, journal = {Wellcome open research}, volume = {9}, number = {}, pages = {488}, pmid = {39386965}, issn = {2398-502X}, support = {/WT_/Wellcome Trust/United Kingdom ; }, abstract = {Critical knowledge gaps have impeded progress towards reducing the global burden of disease due to Mycobacterium ulcerans, the cause of the neglected tropical disease Buruli ulcer (BU). Development of a controlled human infection model of BU has been proposed as an experimental platform to explore host-pathogen interactions and evaluate tools for prevention, diagnosis, and treatment. We have previously introduced the use case for a new human model and identified M. ulcerans JKD8049 as a suitable challenge strain. Here, we present a provisional protocol for an initial study, for transparent peer review during the earliest stages of protocol development. Following simultaneous scientific peer review and community/stakeholder consultation of this provisional protocol, we aim to present a refined protocol for institutional review board (IRB) evaluation.}, }
@article {pmid39383990, year = {2024}, author = {Wang, C and Song, Y and Liang, J and Wang, Y and Zhang, D and Zhao, Z}, title = {Antibiotic resistance genes are transferred from manure-contaminated water bodies to the gut microbiota of animals through the food chain.}, journal = {Environmental pollution (Barking, Essex : 1987)}, volume = {363}, number = {Pt 1}, pages = {125087}, doi = {10.1016/j.envpol.2024.125087}, pmid = {39383990}, issn = {1873-6424}, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; *Food Chain ; *Drug Resistance, Microbial/genetics ; *Manure/microbiology ; Daphnia/genetics ; Feces/microbiology ; Genes, Bacterial ; Anti-Bacterial Agents/pharmacology ; Bacteria/genetics ; Water Pollutants, Chemical ; }, abstract = {Fecal-contaminated water may enter the food chain and become an important route for the transmission of antibiotic resistance genes (ARGs) to the human microbiome. However, little is known about the spread of ARGs from fecal contamination in water bodies along the aquatic food chain. In this study, laboratory-raised Daphnia magna and Aristichthys nobilis were used to investigate the effects of the addition of manure on target ARGs in water and their intestinal contents to determine the potential transmission route of ARGs in the aquatic food chain system. The abundance of target ARGs in water as well as D. magna and A. nobilis intestinal contents significantly increased when fecal contamination was present. ARGs bioaccumulated along the food chain, with four ARGs (tetM-01, tetX, qnrS, and sul2) detected regularly. Mn and Cr were key environmental factors that promoted the transfer of ARGs along the food chain. Fecal addition significantly changed the structure of microbial communities in water, D. magna gut, and A. nobilis gut. The ARG spectrum was significantly correlated with the composition and structure of the bacterial community. Proteobacteria, Bacteroidetes, and Firmicutes were identified as the main host bacteria and were likely to act as carriers of ARGs to promote the spread of antibiotic resistance in the food chain. The composition and structure of bacterial communities, along with mobile genetic elements, were two key drivers of ARG transfer. These findings provide new insights into the distribution and spread of ARGs along the freshwater food chain.}, }
@article {pmid39378356, year = {2025}, author = {Yang, I and Alford, T and Brewster, G and Geurs, N and Wharton, W and Yeager, K and Houser, M}, title = {Oral Microbiome and Cognition Among Black Cancer Caregivers.}, journal = {Nursing research}, volume = {74}, number = {1}, pages = {47-55}, pmid = {39378356}, issn = {1538-9847}, support = {P30 NR018090/NR/NINR NIH HHS/United States ; UL1 TR002378/TR/NCATS NIH HHS/United States ; }, mesh = {Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; *Black or African American/psychology ; *Caregivers/psychology ; Cognition/physiology ; Georgia ; *Microbiota ; Mouth/microbiology ; *Neoplasms/psychology/microbiology ; Oral Health/statistics &amp; numerical data ; Saliva/microbiology ; }, abstract = {BACKGROUND: Despite known links between oral health and dementia and the growing understanding of the role of the human microbiome in health, few studies have explored the relationship between the oral microbiome and cognition. Additionally, there is a notable absence of research on how the oral microbiome is associated with cognitive function in Black adult caregivers of cancer patients despite their elevated risk for both oral disease and cognitive impairment.<br><br>OBJECTIVES: This study aimed to characterize the oral microbiome of Black caregivers of people living with cancer and explore the association of the oral microbiome with cognitive performance.<br><br>METHODS: Thirty-one self-identified Black or African American caregivers of cancer patients in the greater metropolitan Atlanta area participated in the study. They provided oral microbiome samples. Cognitive performance was assessed using the Montreal Cognitive Assessment (MoCA), depressive symptoms with the Center for Epidemiological Studies-Depression Scale, and individual race-related stress with the Index of Race-Related Stress-Brief. Salivary microbiome diversity was analyzed using alpha and beta diversity metrics, and taxa associated with cognition were identified through differential abundance testing, adjusting for potential confounders.<br><br>RESULTS: The mean age of participants was 54.8 years. MoCA scores ranged from 18 to 30, with a mean of 25. Participants were categorized into normal cognition (MoCA &#x2265; 26, n = 12) and low cognition (MoCA < 26, n = 16) groups. Education level and individual race-related stress were associated with cognition group and were controlled for in the oral microbiome analysis. Alpha and beta diversity analyses showed no significant overall differences between cognition groups. Differential abundance testing suggested 48 taxa were associated with cognition status, many of which are known to be associated with periodontal disease and cognition.<br><br>DISCUSSION: This study revealed associations between cognition status and specific oral bacteria, many of which are known to be associated with periodontal disease and cognitive impairment. These findings underscore the complex relationship between oral health and cognitive function, suggesting a need for further research to develop oral microbiome profiles capable of identifying individuals at risk for cognitive decline and guiding targeted interventions for promoting overall well-being and cognitive health.}, }
@article {pmid39377779, year = {2024}, author = {Porreca, A and Ibrahimi, E and Maturo, F and Marcos Zambrano, LJ and Meto, M and Lopes, MB}, title = {Robust prediction of colorectal cancer via gut microbiome 16S rRNA sequencing data.}, journal = {Journal of medical microbiology}, volume = {73}, number = {10}, pages = {}, doi = {10.1099/jmm.0.001903}, pmid = {39377779}, issn = {1473-5644}, mesh = {*RNA, Ribosomal, 16S/genetics ; *Colorectal Neoplasms/microbiology ; Humans ; *Gastrointestinal Microbiome/genetics ; *Machine Learning ; *Feces/microbiology ; Bacteria/genetics/classification/isolation &amp; purification ; }, abstract = {Introduction. The study addresses the challenge of utilizing human gut microbiome data for the early detection of colorectal cancer (CRC). The research emphasizes the potential of using machine learning techniques to analyze complex microbiome datasets, providing a non-invasive approach to identifying CRC-related microbial markers.Hypothesis/Gap Statement. The primary hypothesis is that a robust machine learning-based analysis of 16S rRNA microbiome data can identify specific microbial features that serve as effective biomarkers for CRC detection, overcoming the limitations of classical statistical models in high-dimensional settings.Aim. The primary objective of this study is to explore and validate the potential of the human microbiome, specifically in the colon, as a valuable source of biomarkers for colorectal cancer (CRC) detection and progression. The focus is on developing a classifier that effectively predicts the presence of CRC and normal samples based on the analysis of three previously published faecal 16S rRNA sequencing datasets.Methodology. To achieve the aim, various machine learning techniques are employed, including random forest (RF), recursive feature elimination (RFE) and a robust correlation-based technique known as the fuzzy forest (FF). The study utilizes these methods to analyse the three datasets, comparing their performance in predicting CRC and normal samples. The emphasis is on identifying the most relevant microbial features (taxa) associated with CRC development via partial dependence plots, i.e. a machine learning tool focused on explainability, visualizing how a feature influences the predicted outcome.Results. The analysis of the three faecal 16S rRNA sequencing datasets reveals the consistent and superior predictive performance of the FF compared to the RF and RFE. Notably, FF proves effective in addressing the correlation problem when assessing the importance of microbial taxa in explaining the development of CRC. The results highlight the potential of the human microbiome as a non-invasive means to detect CRC and underscore the significance of employing FF for improved predictive accuracy.Conclusion. In conclusion, this study underscores the limitations of classical statistical techniques in handling high-dimensional information such as human microbiome data. The research demonstrates the potential of the human microbiome, specifically in the colon, as a valuable source of biomarkers for CRC detection. Applying machine learning techniques, particularly the FF, is a promising approach for building a classifier to predict CRC and normal samples. The findings advocate for integrating FF to overcome the challenges associated with correlation when identifying crucial microbial features linked to CRC development.}, }
@article {pmid39375475, year = {2025}, author = {Turocy, T and Crawford, JM}, title = {Bacterial small molecule metabolites implicated in gastrointestinal cancer development.}, journal = {Nature reviews. Microbiology}, volume = {23}, number = {2}, pages = {106-121}, pmid = {39375475}, issn = {1740-1534}, mesh = {Humans ; *Gastrointestinal Neoplasms/metabolism/microbiology/etiology ; *Gastrointestinal Microbiome ; *Bacteria/metabolism/genetics ; Animals ; }, abstract = {Numerous associations have been identified between cancer and the composition and function of the human microbiome. As cancer remains the second leading global cause of mortality, investigating the carcinogenic contributions of microbiome members could advance our understanding of cancer risk and support potential therapeutic interventions. Although fluctuations in bacterial species have been associated with cancer progression, studying their small molecule metabolites offers one avenue to establish support for causal relationships and the molecular mechanisms governing host-microorganism interactions. In this Review, we explore the expanding repertoire of small molecule metabolites and their mechanisms implicated in the risk of developing gastrointestinal cancers.}, }
@article {pmid39368472, year = {2024}, author = {El Mouali, Y and Tawk, C and Huang, KD and Amend, L and Lesker, TR and Ponath, F and Vogel, J and Strowig, T}, title = {The RNA landscape of the human commensal Segatella copri reveals a small RNA essential for gut colonization.}, journal = {Cell host &amp; microbe}, volume = {32}, number = {11}, pages = {1910-1926.e6}, doi = {10.1016/j.chom.2024.09.008}, pmid = {39368472}, issn = {1934-6069}, mesh = {Humans ; Animals ; *Gastrointestinal Microbiome/genetics ; Mice ; *Symbiosis ; *RNA, Bacterial/genetics ; *Germ-Free Life ; Gene Expression Regulation, Bacterial ; Fructans/metabolism ; Mice, Inbred C57BL ; Gastrointestinal Tract/microbiology ; Transcriptome ; }, abstract = {The bacterium Segatella copri is a prevalent member of the human gut microbiota associated with health and disease states. However, the intrinsic factors that determine its ability to colonize the gut effectively remain largely unknown. By extensive transcriptome mapping of S. copri and examining human-derived samples, we discover a small RNA, which we name Segatella RNA colonization factor (SrcF), and show that SrcF is essential for S. copri gut colonization in gnotobiotic mice. SrcF regulates genes involved in nutrient acquisition, and complex carbohydrates, particularly fructans, control its expression. Furthermore, SrcF expression is strongly influenced by human microbiome composition and by the breakdown of fructans by cohabitating commensals, suggesting that the breakdown of complex carbohydrates mediates interspecies signaling among commensals beyond its established function in generating energy. Together, this study highlights the contribution of a small RNA as a critical regulator in gut colonization.}, }
@article {pmid39365053, year = {2024}, author = {Silk, ET and Bayer, SB and Foster, M and Roy, NC and Taylor, MW and Vatanen, T and Gearry, RB}, title = {Advancing microbiome research in Māori populations: insights from recent literature exploring the gut microbiomes of underrepresented and Indigenous peoples.}, journal = {mSystems}, volume = {9}, number = {11}, pages = {e0090924}, pmid = {39365053}, issn = {2379-5077}, support = {Doctoral Scholarship//University of Otago (Te Whare W&#x101;nanga o Ot&#x101;go)/ ; HRC 23/314//Manatu Hauora | Health Research Council of New Zealand (HRC)/ ; UOAX1421,UOAX1902//High Value Nutrition (New Zealand)/ ; }, mesh = {Humans ; *Gastrointestinal Microbiome ; *Indigenous Peoples ; Maori People ; }, abstract = {The gut microbiome plays vital roles in human health, including mediating metabolism, immunity, and the gut-brain axis. Many ethnicities remain underrepresented in gut microbiome research, with significant variation between Indigenous and non-Indigenous peoples due to dietary, socioeconomic, health, and urbanization differences. Although research regarding the microbiomes of Indigenous peoples is increasing, Māori microbiome literature is lacking despite widespread inequities that Māori populations face. These inequities likely contribute to gut microbiome differences that exacerbate negative health outcomes. Characterizing the gut microbiomes of underrepresented populations is necessary to inform efforts to address health inequities. However, for microbiome research to be culturally responsible and meaningful, study design must improve to better protect the rights and interests of Indigenous peoples. Here, we discuss barriers to Indigenous participation in research and the role disparities may play in shaping the gut microbiomes of Indigenous peoples, with a particular focus on implications for Māori and areas for improvement.}, }
@article {pmid39362115, year = {2024}, author = {Tian, H and Tang, R}, title = {Prediction of Crohn's disease based on deep feature recognition.}, journal = {Computational biology and chemistry}, volume = {113}, number = {}, pages = {108231}, doi = {10.1016/j.compbiolchem.2024.108231}, pmid = {39362115}, issn = {1476-928X}, mesh = {*Crohn Disease/genetics ; Humans ; *Deep Learning ; Support Vector Machine ; }, abstract = {BACKGROUND: Crohn's disease is a complex genetic disease that involves chronic gastrointestinal inflammation and results from a complex set of genetic, environmental, and immunological factors. By analyzing data from the human microbiome, genetic information can be used to predict Crohn's disease. Recent advances in deep learning have demonstrated its effectiveness in feature extraction and the use of deep learning to decode genetic information for disease prediction.<br><br>METHODS: In this paper, we present a deep learning-based model that utilizes a sequential convolutional attention network (SCAN) for feature extraction, incorporates adaptive additive interval losses to enhance these features, and employs support vector machines (SVM) for classification. To address the challenge of unbalanced Crohn's disease samples, we propose a random noise one-hot encoding data augmentation method.<br><br>RESULTS: Data augmentation with random noise accelerates training convergence, while SCAN-SVM effectively extracts features with adaptive additive interval loss enhancing differentiation. Our approach outperforms benchmark methods, achieving an average accuracy of 0.80 and a kappa value of 0.76, and we validate the effectiveness of feature enhancement.<br><br>CONCLUSIONS: In summary, we use deep feature recognition to effectively analyze the potential information in genes, which has a good application potential for gene analysis and prediction of Crohn's disease.}, }
@article {pmid39359681, year = {2024}, author = {Tian, S and Ding, T and Li, H}, title = {Oral microbiome in human health and diseases.}, journal = {mLife}, volume = {3}, number = {3}, pages = {367-383}, pmid = {39359681}, issn = {2770-100X}, abstract = {The oral cavity contains the second-largest microbiota in the human body. The cavity's anatomically and physiologically diverse niches facilitate a wide range of symbiotic bacteria living at distinct oral sites. Consequently, the oral microbiota exhibits site specificity, with diverse species, compositions, and structures influenced by specific aspects of their placement. Variations in oral microbiota structure caused by changes in these influencing factors can impact overall health and lead to the development of diseases-not only in the oral cavity but also in organs distal to the mouth-such as cancer, cardiovascular disease, and respiratory disease. Conversely, diseases can exacerbate the imbalance of the oral microbiota, creating a vicious cycle. Understanding the heterogeneity of both the oral microbiome and individual humans is important for investigating the causal links between the oral microbiome and diseases. Additionally, understanding the intricacies of the oral microbiome's composition and regulatory factors will help identify the potential causes of related diseases and develop interventions to prevent and treat illnesses in this domain. Therefore, turning to the extant research in this field, we systematically review the relationship between oral microbiome dynamics and human diseases.}, }
@article {pmid39358771, year = {2024}, author = {Kawano-Sugaya, T and Arikawa, K and Saeki, T and Endoh, T and Kamata, K and Matsuhashi, A and Hosokawa, M}, title = {A single amplified genome catalog reveals the dynamics of mobilome and resistome in the human microbiome.}, journal = {Microbiome}, volume = {12}, number = {1}, pages = {188}, pmid = {39358771}, issn = {2049-2618}, mesh = {Humans ; *Bacteria/genetics/classification ; *Gastrointestinal Microbiome/genetics ; *Metagenome ; *Mouth/microbiology ; *Genome, Bacterial ; Interspersed Repetitive Sequences/genetics ; Microbiota/genetics ; Drug Resistance, Bacterial/genetics ; Metagenomics/methods ; Phylogeny ; }, abstract = {BACKGROUND: The increase in metagenome-assembled genomes (MAGs) has advanced our understanding of the functional characterization and taxonomic assignment within the human microbiome. However, MAGs, as population consensus genomes, often aggregate heterogeneity among species and strains, thereby obfuscating the precise relationships between microbial hosts and mobile genetic elements (MGEs). In contrast, single amplified genomes (SAGs) derived via single-cell genome sequencing can capture individual genomic content, including MGEs.<br><br>RESULTS: We introduce the first substantial SAG dataset (bbsag20) from the human oral and gut microbiome, comprising 17,202 SAGs above medium-quality without co-assembly. This collection unveils a diversity of bacterial lineages across 312 oral and 647 gut species, demonstrating different taxonomic compositions from MAGs. Moreover, the SAGs showed cellular-level evidence of the translocation of oral bacteria to the gut. We also identified broad-host-range MGEs harboring antibiotic resistance genes (ARGs), which were not detected in the MAGs.<br><br>CONCLUSIONS: The difference in taxonomic composition between SAGs and MAGs indicates that combining both methods would be effective in expanding the genome catalog. By connecting mobilomes and resistomes in individual samples, SAGs could meticulously chart a dynamic network of ARGs on MGEs, pinpointing potential ARG reservoirs and their spreading patterns in the microbial community. Video Abstract.}, }
@article {pmid39358005, year = {2024}, author = {Manning, S and Sinha, R and Rees, CJ}, title = {Need for standardised approaches to human microbiome research using the example of colorectal neoplasia research.}, journal = {Gut}, volume = {}, number = {}, pages = {}, doi = {10.1136/gutjnl-2024-333765}, pmid = {39358005}, issn = {1468-3288}, }
@article {pmid39352141, year = {2024}, author = {Coclet, C and Camargo, AP and Roux, S}, title = {MVP: a modular viromics pipeline to identify, filter, cluster, annotate, and bin viruses from metagenomes.}, journal = {mSystems}, volume = {9}, number = {10}, pages = {e0088824}, pmid = {39352141}, issn = {2379-5077}, mesh = {*Metagenome/genetics ; *Genome, Viral/genetics ; *Metagenomics/methods ; *Viruses/genetics/classification/isolation &amp; purification ; Software ; Virome/genetics ; Computational Biology/methods ; Molecular Sequence Annotation ; }, abstract = {While numerous computational frameworks and workflows are available for recovering prokaryote and eukaryote genomes from metagenome data, only a limited number of pipelines are designed specifically for viromics analysis. With many viromics tools developed in the last few years alone, it can be challenging for scientists with limited bioinformatics experience to easily recover, evaluate quality, annotate genes, dereplicate, assign taxonomy, and calculate relative abundance and coverage of viral genomes using state-of-the-art methods and standards. Here, we describe Modular Viromics Pipeline (MVP) v.1.0, a user-friendly pipeline written in Python and providing a simple framework to perform standard viromics analyses. MVP combines multiple tools to enable viral genome identification, characterization of genome quality, filtering, clustering, taxonomic and functional annotation, genome binning, and comprehensive summaries of results that can be used for downstream ecological analyses. Overall, MVP provides a standardized and reproducible pipeline for both extensive and robust characterization of viruses from large-scale sequencing data including metagenomes, metatranscriptomes, viromes, and isolate genomes. As a typical use case, we show how the entire MVP pipeline can be applied to a set of 20 metagenomes from wetland sediments using only 10 modules executed via command lines, leading to the identification of 11,656 viral contigs and 8,145 viral operational taxonomic units (vOTUs) displaying a clear beta-diversity pattern. Further, acting as a dynamic wrapper, MVP is designed to continuously incorporate updates and integrate new tools, ensuring its ongoing relevance in the rapidly evolving field of viromics. MVP is available at https://gitlab.com/ccoclet/mvp and as versioned packages in PyPi and Conda.IMPORTANCEThe significance of our work lies in the development of Modular Viromics Pipeline (MVP), an integrated and user-friendly pipeline tailored exclusively for viromics analyses. MVP stands out due to its modular design, which ensures easy installation, execution, and integration of new tools and databases. By combining state-of-the-art tools such as geNomad and CheckV, MVP provides high-quality viral genome recovery and taxonomy and host assignment, and functional annotation, addressing the limitations of existing pipelines. MVP's ability to handle diverse sample types, including environmental, human microbiome, and plant-associated samples, makes it a versatile tool for the broader microbiome research community. By standardizing the analysis process and providing easily interpretable results, MVP enables researchers to perform comprehensive studies of viral communities, significantly advancing our understanding of viral ecology and its impact on various ecosystems.}, }
@article {pmid39351241, year = {2024}, author = {Lu, S and Wang, C and Ma, J and Wang, Y}, title = {Metabolic mediators: microbial-derived metabolites as key regulators of anti-tumor immunity, immunotherapy, and chemotherapy.}, journal = {Frontiers in immunology}, volume = {15}, number = {}, pages = {1456030}, pmid = {39351241}, issn = {1664-3224}, mesh = {Humans ; *Neoplasms/immunology/therapy/metabolism/drug therapy ; *Immunotherapy/methods ; *Gastrointestinal Microbiome/immunology ; *Tumor Microenvironment/immunology ; Animals ; *Fatty Acids, Volatile/metabolism ; *Tryptophan/metabolism ; Methylamines/metabolism/immunology ; Antineoplastic Agents/therapeutic use ; }, abstract = {The human microbiome has recently emerged as a focal point in cancer research, specifically in anti-tumor immunity, immunotherapy, and chemotherapy. This review explores microbial-derived metabolites, emphasizing their crucial roles in shaping fundamental aspects of cancer treatment. Metabolites such as short-chain fatty acids (SCFAs), Trimethylamine N-Oxide (TMAO), and Tryptophan Metabolites take the spotlight, underscoring their diverse origins and functions and their profound impact on the host immune system. The focus is on SCFAs' remarkable ability to modulate immune responses, reduce inflammation, and enhance anti-tumor immunity within the intricate tumor microenvironment (TME). The review critically evaluates TMAO, intricately tied to dietary choices and gut microbiota composition, assessing its implications for cancer susceptibility, progression, and immunosuppression. Additionally, the involvement of tryptophan and other amino acid metabolites in shaping immune responses is discussed, highlighting their influence on immune checkpoints, immunosuppression, and immunotherapy effectiveness. The examination extends to their dynamic interaction with chemotherapy, emphasizing the potential of microbial-derived metabolites to alter treatment protocols and optimize outcomes for cancer patients. A comprehensive understanding of their role in cancer therapy is attained by exploring their impacts on drug metabolism, therapeutic responses, and resistance development. In conclusion, this review underscores the pivotal contributions of microbial-derived metabolites in regulating anti-tumor immunity, immunotherapy responses, and chemotherapy outcomes. By illuminating the intricate interactions between these metabolites and cancer therapy, the article enhances our understanding of cancer biology, paving the way for the development of more effective treatment options in the ongoing battle against cancer.}, }
@article {pmid39349378, year = {2024}, author = {Palmer, D and Henze, L and Murua Escobar, H and Walter, U and Kowald, A and Fuellen, G}, title = {Multicohort study testing the generalisability of the SASKit-ML stroke and PDAC prognostic model pipeline to other chronic diseases.}, journal = {BMJ open}, volume = {14}, number = {9}, pages = {e088181}, pmid = {39349378}, issn = {2044-6055}, mesh = {Humans ; *Diabetes Mellitus, Type 2/complications ; Prognosis ; Female ; Male ; *Pancreatic Neoplasms ; *Stroke ; Middle Aged ; Arthritis, Rheumatoid ; Machine Learning ; Inflammatory Bowel Diseases ; Aged ; Longitudinal Studies ; Chronic Disease ; Prospective Studies ; Biomarkers/blood ; Cohort Studies ; }, abstract = {OBJECTIVES: To validate and test the generalisability of the SASKit-ML pipeline, a prepublished feature selection and machine learning pipeline for the prediction of health deterioration after a stroke or pancreatic adenocarcinoma event, by using it to identify biomarkers of health deterioration in chronic disease.<br><br>DESIGN: This is a validation study using a predefined protocol applied to multiple publicly available datasets, including longitudinal data from cohorts with type 2 diabetes (T2D), inflammatory bowel disease (IBD), rheumatoid arthritis (RA) and various cancers. The datasets were chosen to mimic as closely as possible the SASKit cohort, a prospective, longitudinal cohort study.<br><br>DATA SOURCES: Public data were used from the T2D (77 patients with potential pre-diabetes and 18 controls) and IBD (49 patients with IBD and 12 controls) branches of the Human Microbiome Project (HMP), RA Map (RA-MAP, 92 patients with RA, 22 controls) and The Cancer Genome Atlas (TCGA, 16 cancers).<br><br>METHODS: Data integration steps were performed in accordance with the prepublished study protocol, generating features to predict disease outcomes using 10-fold cross-validated random survival forests.<br><br>OUTCOME MEASURES: Health deterioration was assessed using disease-specific clinical markers and endpoints across different cohorts. In the HMP-T2D cohort, the worsening of glycated haemoglobin (HbA1c) levels (5.7% or more HbA1c in the blood), fasting plasma glucose (at least 100&#x2009;mg/dL) and oral glucose tolerance test (at least 140) results were considered. For the HMP-IBD cohort, a worsening by at least 3 points of a disease-specific severity measure, the "Simple Clinical Colitis Activity Index" or "Harvey-Bradshaw Index" indicated an event. For the RA-MAP cohort, the outcome was defined as the worsening of the "Disease Activity Score 28" or "Simple Disease Activity Index" by at least five points, or the worsening of the "Health Assessment Questionnaire" score or an increase in the number of swollen/tender joints were evaluated. Finally, the outcome for all TCGA datasets was the progression-free interval.<br><br>RESULTS: Models for the prediction of health deterioration in T2D, IBD, RA and 16 cancers were produced. The T2D (C-index of 0.633 and Integrated Brier Score (IBS) of 0.107) and the RA (C-index of 0.654 and IBS of 0.150) models were modestly predictive. The IBD model was uninformative. TCGA models tended towards modest predictive power.<br><br>CONCLUSIONS: The SASKit-ML pipeline produces informative and useful features with the power to predict health deterioration in a variety of diseases and cancers; however, this performance is disease-dependent.}, }
@article {pmid39345212, year = {2024}, author = {Basting, CM and Langat, R and Broedlow, CA and Guerrero, CR and Bold, TD and Bailey, M and Velez, A and Schroeder, T and Short-Miller, J and Cromarty, R and Mayer, ZJ and Southern, PJ and Schacker, TW and Safo, SE and Bramante, CT and Tignanelli, CJ and Schifanella, L and Klatt, NR}, title = {SARS-CoV-2 infection is associated with intestinal permeability, systemic inflammation, and microbial dysbiosis in hospitalized patients.}, journal = {Microbiology spectrum}, volume = {12}, number = {11}, pages = {e0068024}, pmid = {39345212}, issn = {2165-0497}, mesh = {Humans ; *COVID-19/microbiology ; *Dysbiosis/microbiology ; Male ; Female ; Middle Aged ; *SARS-CoV-2/isolation &amp; purification ; *Inflammation ; *Gastrointestinal Microbiome ; Aged ; Adult ; RNA, Ribosomal, 16S/genetics ; Permeability ; Cytokines/blood ; Hospitalization ; Bacteria/classification/isolation &amp; purification/genetics ; Intestinal Barrier Function ; }, abstract = {Coronavirus disease 2019 (COVID-19) and its associated severity have been linked to uncontrolled inflammation and may be associated with changes in the microbiome of mucosal sites including the gastrointestinal tract and oral cavity. These sites play an important role in host-microbe homeostasis, and disruption of epithelial barrier integrity during COVID-19 may potentially lead to exacerbated inflammation and immune dysfunction. Outcomes in COVID-19 are highly disparate, ranging from asymptomatic to fatal, and the impact of microbial dysbiosis on disease severity is unclear. Here, we obtained plasma, rectal swabs, oropharyngeal swabs, and nasal swabs from 86 patients hospitalized with COVID-19 and 12 healthy volunteers. We performed 16S rRNA sequencing to characterize the microbial communities in the mucosal swabs and measured concentrations of circulating cytokines, markers of gut barrier integrity, and fatty acids in the plasma samples. We compared these plasma concentrations and microbiomes between healthy volunteers and COVID-19 patients, some of whom had unfortunately died by the end of the study enrollment, and performed a correlation analysis between plasma variables and bacterial abundances. Rectal swabs of COVID-19 patients had reduced abundances of several commensal bacteria including Faecalibacterium prausnitzii and an increased abundance of the opportunistic pathogens Eggerthella lenta and Hungatella hathewayi. Furthermore, the oral pathogen Scardovia wiggsiae was more abundant in the oropharyngeal swabs of COVID-19 patients who died. The abundance of both H. hathewayi and S. wiggsiae correlated with circulating inflammatory markers including IL-6, highlighting the possible role of the microbiome in COVID-19 severity and providing potential therapeutic targets for managing COVID-19.IMPORTANCEOutcomes in coronavirus disease 2019 (COVID-19) are highly disparate and are associated with uncontrolled inflammation; however, the individual factors that lead to this uncontrolled inflammation are not fully understood. Here, we report that severe COVID-19 is associated with systemic inflammation, microbial translocation, and microbial dysbiosis. The rectal and oropharyngeal microbiomes of COVID-19 patients were characterized by a decreased abundance of commensal bacteria and an increased abundance of opportunistic pathogens, which positively correlated with markers of inflammation and microbial translocation. These microbial perturbations may, therefore, contribute to disease severity in COVID-19 and highlight the potential for microbiome-based interventions in improving COVID-19 outcomes.}, }
@article {pmid39342083, year = {2024}, author = {Wang, X and Yao, S and Yang, X and Li, Y and Yu, Z and Huang, J and Wang, J}, title = {Peritoneal dialysis promotes microbial-driven biosynthesis pathways of sesquiterpenes and triterpenes compounds in end-stage renal disease patients.}, journal = {BMC microbiology}, volume = {24}, number = {1}, pages = {377}, pmid = {39342083}, issn = {1471-2180}, support = {32170071//National Natural Science Foundation of China/ ; 32300051//National Natural Science Foundation of China/ ; 2022JJ40663//Natural Science Foundation of Hunan Province/ ; C2023045//Hunan Province Traditional Chinese Medicine Research Program Project/ ; }, mesh = {Humans ; *Kidney Failure, Chronic/therapy/metabolism/microbiology ; *Gastrointestinal Microbiome ; *Peritoneal Dialysis ; *Sesquiterpenes/metabolism ; Male ; Female ; *Feces/microbiology ; Middle Aged ; *Triterpenes/metabolism ; Bacteria/metabolism/classification/genetics/isolation &amp; purification ; Biosynthetic Pathways ; Adult ; Metagenomics ; Aged ; }, abstract = {The concept of the gut-kidney axis is gaining significant attention due to the close relationship between gut microbiota and kidney disease. Peritoneal dialysis is recognized as a crucial renal replacement therapy for end-stage renal disease (ESRD). The alterations in gut microbiota and related mechanisms after receiving this dialysis method are not fully understood. This study conducted shotgun metagenomic sequencing on fecal samples from 11 end-stage renal disease patients who did not receive dialysis (ESRD_N) and 7 patients who received peritoneal dialysis (ESRD_P). After quality control and correlation analysis of the data, our study is aimed at exploring the impact of peritoneal dialysis on the gut microbiota and health of ESRD patients. Our research findings indicate that the complexity and aggregation characteristics of gut microbiota interactions increase in ESRD_P. In addition, the gut microbiota drives the biosynthesis pathways of sesquiterpenes and triterpenes in ESRD_P patients, which may contribute to blood purification and improve circulation. Therefore, our research will lay the foundation for the prevention and treatment of ESRD.}, }
@article {pmid39341037, year = {2024}, author = {Vogs, C and Lindqvist, D and Wai Tang, S and Gugescu, L and Alenius, H and Wincent, E}, title = {Transcriptomic and functional effects from a chemical mixture based on the exposure profile in Baltic Sea salmon, on metabolic and immune functions in zebrafish embryo.}, journal = {Environment international}, volume = {192}, number = {}, pages = {109018}, doi = {10.1016/j.envint.2024.109018}, pmid = {39341037}, issn = {1873-6750}, mesh = {Animals ; *Zebrafish ; *Water Pollutants, Chemical/toxicity ; *Transcriptome/drug effects ; *Salmon ; Embryo, Nonmammalian/drug effects ; Hydrocarbons, Halogenated/toxicity ; Gene Expression Profiling ; }, abstract = {The Baltic Sea is one of the world's most contaminated seas with long-standing adverse health status of its wildlife such as the Baltic Sea salmon, resulting in reduced fecundity and increased mortality. While adverse health effects have been reported among wild fish from the Baltic Sea, the toxicity mechanisms underlying these adversities, and the chemical effect drivers mediating them are poorly understood. To address this knowledge gap, we utilized the zebrafish (Danio rerio) embryo model to determine molecular and functional effects brought on by exposure to a technical mixture including 9 organohalogen compounds detected in serum from wild-caught Baltic Sea salmon. To align with the salmon exposure scenario, an internal dose regimen was opted to establish same relative proportions of the compounds in the zebrafish (whole body) as observed in the salmon serum. Through transcriptomic profiling, we identified dose-dependent effects on immune system and metabolism as two critical functions overlapping with adverse effects observed in wild fish from the Baltic Sea. We then determined likely effect drivers by comparing gene responses of the mixture with those of individual mixture components. Aligned with our transcriptome results, the number of total macrophages was reduced and the zebrafish's ability to respond to a tissue damage suppressed in a dose-dependent manner. This study brings forth a key advancement in delineating the impact of chemical pollutants on the health of wild fish in the Baltic Sea.}, }
@article {pmid39340867, year = {2024}, author = {Moghaddam, HS and Abkar, L and Fowler, SJ}, title = {Making waves: From tap to gut- exploring the impact of drinking water on gut microbiota.}, journal = {Water research}, volume = {267}, number = {}, pages = {122503}, doi = {10.1016/j.watres.2024.122503}, pmid = {39340867}, issn = {1879-2448}, mesh = {*Drinking Water/microbiology ; *Gastrointestinal Microbiome ; Humans ; Diet ; }, abstract = {Drinking water (DW) harbours diverse microbial species and chemical attributes. Water comprises the greatest portion of our daily diet, ingested both on its own and used in the preparation of food. DW is our major source of liquids, which is vital to maintaining homeostasis, and can also supply essential minerals. Limited evidence suggests that DW plays a role in shaping the gut microbiome, which implies that it may impact human health. Despite its significant contribution to diet, DW is often overlooked in studies examining dietary influences on the gut microbiota. This perspective explores our current understanding of the link between DW and the gut microbiota - an area of human microbiome science that has been surprisingly understudied. Existing studies reveal links between DW source, microbiota composition, and gut health, emphasizing the need for comprehensive investigations. Understanding the interplay between DW and gut microbiota holds potential for tailored interventions to enhance human health.}, }
@article {pmid39339787, year = {2024}, author = {Fraiz, GM and Bonifácio, DB and Lacerda, UV and Cardoso, RR and Corich, V and Giacomini, A and Martino, HSD and Echeverría, SE and Barros, FAR and Milagro, FI and Bressan, J}, title = {Green Tea Kombucha Impacts Inflammation and Salivary Microbiota in Individuals with Excess Body Weight: A Randomized Controlled Trial.}, journal = {Nutrients}, volume = {16}, number = {18}, pages = {}, pmid = {39339787}, issn = {2072-6643}, support = {CAPE 507/2019 - APQ-00035-20//Funda&#xe7;&#xe3;o de Amparo &#xe0; Pesquisa do Estado de Minas Gerais/ ; CB12/03/30002//Spanish Biomedical Research Centre in Physiopathology of Obesity and Nutrition/ ; 001//Coordena&#xe7;&#xe3;o de Aperfeicoamento de Pessoal de N&#xed;vel Superior/ ; }, mesh = {Humans ; *Saliva/microbiology ; Male ; Female ; *Inflammation ; Adult ; *Microbiota ; Kombucha Tea ; Middle Aged ; Weight Loss ; Tea ; Overweight/microbiology ; Body Mass Index ; Caloric Restriction ; Body Composition ; }, abstract = {BACKGROUND: Green tea kombucha (GTK) is a fermented beverage with promising health benefits, but few studies proved its impact on human health. Thus, we aimed to investigate the impact of GTK on weight loss, inflammation, and salivary microbiota in individuals with excess body weight.<br><br>METHODS: This is a randomized controlled clinical trial that lasted 10 weeks with two groups of individuals with excess body weight: control (CG; n = 29; caloric restriction) and kombucha (KG; n = 30; caloric restriction + 200 mL GTK). Body composition, anthropometry, saliva, and blood collection were performed in the beginning and end of the intervention. Plasma interleukins were determined by flow cytometry. Salivary microbiota was analyzed by 16S rRNA sequencing.<br><br>RESULTS: Both groups decreased weight, BMI, and body fat (p < 0.001) after the intervention, but there were no differences between groups. The KG reduced lipid accumulation product (LAP) (p = 0.029). Both groups decreased IL-1&#x3b2; and IL-8, but IL-6 increased in the CG (p = 0.023) compared to the kombucha group. Alpha and beta diversity of salivary microbiota increased in the KG. Moreover, the KG presented lower Bacillota/Bacteroidota ratio (p = 0.028), and BMI was positively associated with the Bacillota phylum.<br><br>CONCLUSIONS: GTK did not enhance weight loss, but it decreased the LAP. GTK helped in the inflammatory profile and induced positive changes in oral microbiota composition.}, }
@article {pmid39337688, year = {2024}, author = {Fleshner, L and Roster, K and Farabi, B and Hirani, R and Tepper, K and Pitchumoni, CS and Safai, B and Marmon, S}, title = {Follicular Skin Disorders, Inflammatory Bowel Disease, and the Microbiome: A Systematic Review.}, journal = {International journal of molecular sciences}, volume = {25}, number = {18}, pages = {}, pmid = {39337688}, issn = {1422-0067}, mesh = {Humans ; *Dysbiosis/microbiology ; *Gastrointestinal Microbiome ; Hidradenitis Suppurativa/microbiology ; *Inflammatory Bowel Diseases/microbiology ; Microbiota ; Skin/microbiology ; Skin Diseases/microbiology ; }, abstract = {Follicular skin disorders, including hidradenitis suppurativa (HS), frequently coexist with systemic autoinflammatory diseases, such as inflammatory bowel disease (IBD) and its subtypes, Crohn's disease and ulcerative colitis. Previous studies suggest that dysbiosis of the human gut microbiome may serve as a pathogenic link between HS and IBD. However, the role of the microbiome (gut, skin, and blood) in the context of IBD and various follicular disorders remains underexplored. Here, we performed a systematic review to investigate the relationship between follicular skin disorders, IBD, and the microbiome. Of the sixteen included studies, four evaluated the impact of diet on the microbiome in HS patients, highlighting a possible link between gut dysbiosis and yeast-exclusion diets. Ten studies explored bacterial colonization and HS severity with specific gut and skin microbiota, including Enterococcus and Veillonella. Two studies reported on immunological or serological biomarkers in HS patients with autoinflammatory disease, including IBD, and identified common markers including elevated cytokines and T-lymphocytes. Six studies investigated HS and IBD patients concurrently. Our systematic literature review highlights the complex interplay between the human microbiome, IBD, and follicular disorders with a particular focus on HS. The results indicate that dietary modifications hold promise as a therapeutic intervention to mitigate the burden of HS and IBD. Microbiota analyses and the identification of key serological biomarkers are crucial for a deeper understanding of the impact of dysbiosis in these conditions. Future research is needed to more thoroughly delineate the causal versus associative roles of dysbiosis in patients with both follicular disorders and IBD.}, }
@article {pmid39337215, year = {2024}, author = {Falara, E and Metallinou, D and Nanou, C and Vlachou, M and Diamanti, A}, title = {Perinatal Exposure to Tobacco Smoke and Its Association with the Maternal and Offspring Microbiome: A Systematic Review.}, journal = {Healthcare (Basel, Switzerland)}, volume = {12}, number = {18}, pages = {}, pmid = {39337215}, issn = {2227-9032}, support = {The APC was partially funded by the "Special Account for Research Grants" of the University of West Attica, Athens, Greece.//The APC was partially funded by the "Special Account for Research Grants" of the University of West Attica, Athens, Greece./ ; }, abstract = {BACKGROUND: The human microbiome, comprising trillions of microorganisms, significantly influences human health and disease. During critical periods like the perinatal phase, the microbiome undergoes significant changes, impacting lifelong health. Tobacco smoke, a known environmental pollutant, has adverse effects on health, particularly during pregnancy. Despite this, its association with the perinatal microbiome remains understudied.<br><br>METHODS: We conducted a systematic review to integrate findings on perinatal tobacco smoke exposure and its association with the maternal and neonatal microbiomes. We conducted a comprehensive literature search in the PubMed, Scopus, and Web of Science databases from January 2000 to February 2024. We selected studies that met predefined inclusion criteria and performed data extraction.<br><br>RESULTS: The review included eight studies that revealed diverse associations of perinatal tobacco exposure with the maternal and neonatal microbiome. Active smoking during pregnancy was linked to alterations in microbiome composition and diversity in children. Maternal smoking correlated with increased Firmicutes abundance and decreased Akkermansia muciniphila abundance in offspring. Additionally, exposure to thirdhand smoke in neonatal intensive care units was related to infant microbiome diversity. Infants exposed to tobacco smoke showed various microbial changes, suggesting potential implications for childhood health outcomes, including obesity risk.<br><br>CONCLUSIONS: Perinatal exposure to tobacco smoke exerts significant influence on the maternal and neonatal microbiomes, with potential implications for long-term health outcomes. Addressing socioeconomic and psychological barriers to smoking cessation, implementing stricter smoking regulations, and promoting public health campaigns are essential steps towards reducing tobacco-related harm during the perinatal period. Further longitudinal studies and standardized assessment methods are needed to validate these findings and guide the development of effective preventive measures.}, }
@article {pmid39335616, year = {2024}, author = {Xiang, B and Zhang, Q and Wu, H and Lin, J and Xu, Z and Zhang, M and Zhu, L and Hu, J and Zhi, M}, title = {Impact of Mild COVID-19 History on Oral-Gut Microbiota and Serum Metabolomics in Adult Patients with Crohn's Disease: Potential Beneficial Effects.}, journal = {Biomedicines}, volume = {12}, number = {9}, pages = {}, pmid = {39335616}, issn = {2227-9059}, support = {2014008 (MZ)//the Sun Yat-sen University Clinical Research 5010 Program/ ; 82270544 (MZ)//the National Natural Science Foundation of China/ ; SL2022B03J00237 (MZ)//the Bureau of Science and Technology of Guangzhou Municipality/ ; 2022JBGS06 (MZ)//"Jie Bang Gua Shuai" project of The Sixth Affiliated Hospital of Sun Yat-sen University/ ; 2019ZT08Y464 (LZ)//Guangdong Province "Pearl River Talent Plan" Innovation and Entrepreneurship Team Project/ ; 2020B1111170004 (MZ)//the program of Guangdong Provincial Clinical Research Center for Digestive Diseases/ ; }, abstract = {The impact of coronavirus disease 2019 (COVID-19) history on Crohn's disease (CD) is unknown. This investigation aimed to examine the effect of COVID-19 history on the disease course, oral-gut microbiota, and serum metabolomics in patients with CD. In this study, oral-gut microbiota and serum metabolomic profiles in 30 patients with CD and a history of mild COVID-19 (positive group, PG), 30 patients with CD without COVID-19 history (negative group, NG), and 60 healthy controls (HC) were assessed using 16S rDNA sequencing and targeted metabolomics. During follow-up, the CD activity index showed a stronger decrease in the PG than in the NG (p = 0.0496). PG patients demonstrated higher α-diversity and distinct β-diversity clustering in both salivary and fecal microbiota compared to NG and HC individuals. Notably, the gut microbiota composition in the PG patients showed a significantly greater similarity to that of HC than NG individuals. The interaction between oral and intestinal microbiota in the PG was reduced. Moreover, serum metabolome analysis revealed significantly increased anti-inflammatory metabolites, including short-chain fatty acids and N-Acetylserotonin, among PG patients; meanwhile, inflammation-related metabolites such as arachidonic acid were significantly reduced in this group. Our data suggest that the gut microbiota mediates a potential beneficial effect of a mild COVID-19 history in CD patients.}, }
@article {pmid39334849, year = {2024}, author = {Mukherjee, S and Verma, A and Kong, L and Rengan, AK and Cahill, DM}, title = {Advancements in Green Nanoparticle Technology: Focusing on the Treatment of Clinical Phytopathogens.}, journal = {Biomolecules}, volume = {14}, number = {9}, pages = {}, pmid = {39334849}, issn = {2218-273X}, mesh = {*Nanoparticles/chemistry/therapeutic use ; Humans ; *Anti-Bacterial Agents/pharmacology/chemistry/therapeutic use ; Green Chemistry Technology/methods ; Plant Diseases/microbiology/prevention &amp; control ; }, abstract = {Opportunistic pathogenic microbial infections pose a significant danger to human health, which forces people to use riskier, more expensive, and less effective drugs compared to traditional treatments. These may be attributed to several factors, such as overusing antibiotics in medicine and lack of sanitization in hospital settings. In this context, researchers are looking for new options to combat this worrying condition and find a solution. Nanoparticles are currently being utilized in the pharmaceutical sector; however, there is a persistent worry regarding their potential danger to human health due to the usage of toxic chemicals, which makes the utilization of nanoparticles highly hazardous to eukaryotic cells. Multiple nanoparticle-based techniques are now being developed, offering essential understanding regarding the synthesis of components that play a crucial role in producing anti-microbial nanotherapeutic pharmaceuticals. In this regard, green nanoparticles are considered less hazardous than other forms, providing potential options for avoiding the extensive harm to the human microbiome that is prevalent with existing procedures. This review article aims to comprehensively assess the current state of knowledge on green nanoparticles related to antibiotic activity as well as their potential to assist antibiotics in treating opportunistic clinical phytopathogenic illnesses.}, }
@article {pmid39333709, year = {2024}, author = {Crunkhorn, S}, title = {Identifying antimicrobials in the human microbiome.}, journal = {Nature reviews. Drug discovery}, volume = {23}, number = {11}, pages = {816}, pmid = {39333709}, issn = {1474-1784}, }
@article {pmid39333588, year = {2024}, author = {Garcia-Vello, P and Tytgat, HLP and Elzinga, J and Van Hul, M and Plovier, H and Tiemblo-Martin, M and Cani, PD and Nicolardi, S and Fragai, M and De Castro, C and Di Lorenzo, F and Silipo, A and Molinaro, A and de Vos, WM}, title = {The lipooligosaccharide of the gut symbiont Akkermansia muciniphila exhibits a remarkable structure and TLR signaling capacity.}, journal = {Nature communications}, volume = {15}, number = {1}, pages = {8411}, pmid = {39333588}, issn = {2041-1723}, support = {AdG 250172//EC | EU Framework Programme for Research and Innovation H2020 | H2020 Priority Excellent Science | H2020 European Research Council (H2020 Excellent Science - European Research Council)/ ; }, mesh = {*Lipopolysaccharides ; *Akkermansia ; Animals ; *Signal Transduction ; *Toll-Like Receptor 4/metabolism ; Humans ; *Toll-Like Receptor 2/metabolism ; Mice ; Symbiosis ; Mice, Inbred C57BL ; Lipid A/metabolism/chemistry ; Interleukin-10/metabolism ; Gastrointestinal Microbiome ; Liver/metabolism/microbiology ; Female ; }, abstract = {The cell-envelope of Gram-negative bacteria contains endotoxic lipopolysaccharides (LPS) that are recognized by the innate immune system via Toll-Like Receptors (TLRs). The intestinal mucosal symbiont Akkermansia muciniphila is known to confer beneficial effects on the host and has a Gram-negative architecture. Here we show that A. muciniphila LPS lacks the O-polysaccharide repeating unit, with the resulting lipooligosaccharide (LOS) having unprecedented structural and signaling properties. The LOS consists of a complex glycan chain bearing two distinct undeca- and hexadecasaccharide units each containing three 2-keto-3-deoxy-D-manno-octulosonic acid (Kdo) residues. The lipid A moiety appears as a mixture of differently phosphorylated and acylated species and carries either linear or branched acyl moieties. Peritoneal injection of the LOS in mice increased higher gene expression of liver TLR2 than TLR4 (100-fold) and induced high IL-10 gene expression. A. muciniphila LOS was found to signal both through TLR4 and TLR2, whereas lipid A only induced TLR2 in a human cell line. We propose that the unique structure of the A. muciniphila LOS allows interaction with TLR2, thus generating an anti-inflammatory response as to compensate for the canonical inflammatory signaling associated with LOS and TLR4, rationalizing its beneficial host interaction.}, }
@article {pmid39333143, year = {2024}, author = {Wang, B and Wang, T and Du, X and Li, J and Wang, J and Wu, P}, title = {Microbe-drug association prediction model based on graph convolution and attention networks.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {22327}, pmid = {39333143}, issn = {2045-2322}, support = {145209125//Basic scientific research operations of universities affiliated with Heilongjiang Province/ ; }, mesh = {Humans ; *Deep Learning ; Microbiota ; Computational Biology/methods ; Neural Networks, Computer ; Drug Discovery/methods ; Pharmaceutical Preparations ; }, abstract = {The human microbiome plays a key role in drug development and precision medicine, but understanding its complex interactions with drugs remains a challenge. Identifying microbe-drug associations not only enhances our understanding of their mechanisms but also aids in drug discovery and repurposing. Traditional experiments are expensive and time-consuming, making computational methods for predicting microbe-drug associations a new trend. Currently, computational methods specifically designed for this task are still scarce. Therefore, to address the shortcomings of traditional experimental methods in predicting potential microbe-drug associations, this paper proposes a new prediction model named GCNATMDA. The model combines two deep learning models, Graph Convolutional Network and Graph Attention Network, and aims to reveal potential relationships between microbes and drugs by learning related features. Thus improve the efficiency and accuracy of prediction. We first integrated the microbe-drug association matrix from the existing dataset, and then combined the calculated microbe-drug characteristic matrix as the model input. The GCN module is used to dig deeper into the potential characterization of microbes and drugs, while the GAT module further learns the more complex interactions between them and generates the corresponding score matrix. The experimental results show that the GCNATMDA model achieves 96.59% and 93.01% in AUC and AUPR evaluation indexes, respectively, which is significantly better than the existing prediction models. In addition, the reliability of the prediction results is verified by a series of experiments.}, }
@article {pmid39333099, year = {2024}, author = {Hickman, B and Salonen, A and Ponsero, AJ and Jokela, R and Kolho, KL and de Vos, WM and Korpela, K}, title = {Gut microbiota wellbeing index predicts overall health in a cohort of 1000 infants.}, journal = {Nature communications}, volume = {15}, number = {1}, pages = {8323}, pmid = {39333099}, issn = {2041-1723}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; Infant ; *Feces/microbiology ; Female ; Male ; Infant, Newborn ; Cohort Studies ; Longitudinal Studies ; Child, Preschool ; Bifidobacterium/isolation &amp; purification ; Bacteroides/isolation &amp; purification ; }, abstract = {The human gut microbiota is central in regulating all facets of host physiology, and in early life it is thought to influence the host's immune system and metabolism, affecting long-term health. However, longitudinally monitored cohorts with parallel analysis of faecal samples and health data are scarce. In our observational study we describe the gut microbiota development in the first 2 years of life and create a gut microbiota wellbeing index based on the microbiota development and health data in a cohort of nearly 1000 infants using clustering and trajectory modelling. We show that infants' gut microbiota development is highly predictable, following one of five trajectories, dependent on infant exposures, and predictive of later health outcomes. We characterise the natural healthy gut microbiota trajectory and several different dysbiotic trajectories associated with different health outcomes. Bifidobacterium and Bacteroides appear as early keystone organisms, directing microbiota development and consistently predicting positive health outcomes. A microbiota wellbeing index, based on the healthy development trajectory, is predictive of general health over the first 5 years. The results indicate that gut microbiota succession is part of infant physiological development, predictable, and malleable. This information can be utilised to improve the predictions of individual health risks.}, }
@article {pmid39331660, year = {2024}, author = {Pasqualini, J and Facchin, S and Rinaldo, A and Maritan, A and Savarino, E and Suweis, S}, title = {Emergent ecological patterns and modelling of gut microbiomes in health and in disease.}, journal = {PLoS computational biology}, volume = {20}, number = {9}, pages = {e1012482}, pmid = {39331660}, issn = {1553-7358}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology/genetics ; Models, Biological ; Computational Biology ; Dysbiosis/microbiology ; RNA, Ribosomal, 16S/genetics ; }, abstract = {Recent advancements in next-generation sequencing have revolutionized our understanding of the human microbiome. Despite this progress, challenges persist in comprehending the microbiome's influence on disease, hindered by technical complexities in species classification, abundance estimation, and data compositionality. At the same time, the existence of macroecological laws describing the variation and diversity in microbial communities irrespective of their environment has been recently proposed using 16s data and explained by a simple phenomenological model of population dynamics. We here investigate the relationship between dysbiosis, i.e. in unhealthy individuals there are deviations from the "regular" composition of the gut microbial community, and the existence of macro-ecological emergent law in microbial communities. We first quantitatively reconstruct these patterns at the species level using shotgun data, and addressing the consequences of sampling effects and statistical errors on ecological patterns. We then ask if such patterns can discriminate between healthy and unhealthy cohorts. Concomitantly, we evaluate the efficacy of different statistical generative models, which incorporate sampling and population dynamics, to describe such patterns and distinguish which are expected by chance, versus those that are potentially informative about disease states or other biological drivers. A critical aspect of our analysis is understanding the relationship between model parameters, which have clear ecological interpretations, and the state of the gut microbiome, thereby enabling the generation of synthetic compositional data that distinctively represent healthy and unhealthy individuals. Our approach, grounded in theoretical ecology and statistical physics, allows for a robust comparison of these models with empirical data, enhancing our understanding of the strengths and limitations of simple microbial models of population dynamics.}, }
@article {pmid39327438, year = {2024}, author = {Schmartz, GP and Rehner, J and Gund, MP and Keller, V and Molano, LG and Rupf, S and Hannig, M and Berger, T and Flockerzi, E and Seitz, B and Fleser, S and Schmitt-Grohé, S and Kalefack, S and Zemlin, M and Kunz, M and Götzinger, F and Gevaerd, C and Vogt, T and Reichrath, J and Diehl, L and Hecksteden, A and Meyer, T and Herr, C and Gurevich, A and Krug, D and Hegemann, J and Bozhueyuek, K and Gulder, TAM and Fu, C and Beemelmanns, C and Schattenberg, JM and Kalinina, OV and Becker, A and Unger, M and Ludwig, N and Seibert, M and Stein, ML and Hanna, NL and Martin, MC and Mahfoud, F and Krawczyk, M and Becker, SL and Müller, R and Bals, R and Keller, A}, title = {Decoding the diagnostic and therapeutic potential of microbiota using pan-body pan-disease microbiomics.}, journal = {Nature communications}, volume = {15}, number = {1}, pages = {8261}, pmid = {39327438}, issn = {2041-1723}, mesh = {Humans ; *Microbiota/genetics ; *Metagenome/genetics ; *Metagenomics/methods ; Bacteria/genetics/isolation &amp; purification/classification ; Feces/microbiology ; Male ; Female ; Multigene Family ; Saliva/microbiology ; Adult ; }, abstract = {The human microbiome emerges as a promising reservoir for diagnostic markers and therapeutics. Since host-associated microbiomes at various body sites differ and diseases do not occur in isolation, a comprehensive analysis strategy highlighting the full potential of microbiomes should include diverse specimen types and various diseases. To ensure robust data quality and comparability across specimen types and diseases, we employ standardized protocols to generate sequencing data from 1931 prospectively collected specimens, including from saliva, plaque, skin, throat, eye, and stool, with an average sequencing depth of 5.3 gigabases. Collected from 515 patients, these samples yield an average of 3.7 metagenomes per patient. Our results suggest significant microbial variations across diseases and specimen types, including unexpected anatomical sites. We identify 583 unexplored species-level genome bins (SGBs) of which 189 are significantly disease-associated. Of note, the existence of microbial resistance genes in one specimen was indicative of the same resistance genes in other specimens of the same patient. Annotated and previously undescribed SGBs collectively harbor 28,315 potential biosynthetic gene clusters (BGCs), with 1050 significant correlations to diseases. Our combinatorial approach identifies distinct SGBs and BGCs, emphasizing the value of pan-body pan-disease microbiomics as a source for diagnostic and therapeutic strategies.}, }
@article {pmid39322959, year = {2024}, author = {Wirbel, J and Essex, M and Forslund, SK and Zeller, G}, title = {A realistic benchmark for differential abundance testing and confounder adjustment in human microbiome studies.}, journal = {Genome biology}, volume = {25}, number = {1}, pages = {247}, pmid = {39322959}, issn = {1474-760X}, mesh = {Humans ; *Microbiota ; *Benchmarking ; RNA, Ribosomal, 16S/genetics ; Computer Simulation ; }, abstract = {BACKGROUND: In microbiome disease association studies, it is a fundamental task to test which microbes differ in their abundance between groups. Yet, consensus on suitable or optimal statistical methods for differential abundance testing is lacking, and it remains unexplored how these cope with confounding. Previous differential abundance benchmarks relying on simulated datasets did not quantitatively evaluate the similarity to real data, which undermines their recommendations.<br><br>RESULTS: Our simulation framework implants calibrated signals into real taxonomic profiles, including signals mimicking confounders. Using several whole&#xa0;meta-genome and 16S rRNA gene amplicon datasets, we validate that our simulated data resembles real data from disease association studies much more than in previous benchmarks. With extensively parametrized simulations, we benchmark the performance of nineteen differential abundance methods and further evaluate the best ones on confounded simulations. Only classic statistical methods (linear models, the Wilcoxon test, t-test), limma, and fastANCOM properly control false discoveries at relatively high sensitivity. When additionally considering confounders, these issues are exacerbated, but we find that adjusted differential abundance testing can effectively mitigate them. In a large cardiometabolic disease dataset, we showcase that failure to account for covariates such as medication causes spurious association in real-world applications.<br><br>CONCLUSIONS: Tight error control is critical for microbiome association studies. The unsatisfactory performance of many differential abundance methods and the persistent danger of unchecked confounding suggest these contribute to a lack of reproducibility among such studies. We have open-sourced our simulation and benchmarking software to foster a much-needed consolidation of statistical methodology for microbiome research.}, }
@article {pmid39322314, year = {2024}, author = {Van Hul, M and Cani, PD and Petitfils, C and De Vos, WM and Tilg, H and El-Omar, EM}, title = {What defines a healthy gut microbiome?.}, journal = {Gut}, volume = {73}, number = {11}, pages = {1893-1908}, pmid = {39322314}, issn = {1468-3288}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; Dysbiosis/microbiology ; Probiotics/therapeutic use ; Fecal Microbiota Transplantation ; }, abstract = {The understanding that changes in microbiome composition can influence chronic human diseases and the efficiency of therapies has driven efforts to develop microbiota-centred therapies such as first and next generation probiotics, prebiotics and postbiotics, microbiota editing and faecal microbiota transplantation. Central to microbiome research is understanding how disease impacts microbiome composition and vice versa, yet there is a problematic issue with the term 'dysbiosis', which broadly links microbial imbalances to various chronic illnesses without precision or definition. Another significant issue in microbiome discussions is defining 'healthy individuals' to ascertain what characterises a healthy microbiome. This involves questioning who represents the healthiest segment of our population-whether it is those free from illnesses, athletes at peak performance, individuals living healthily through regular exercise and good nutrition or even elderly adults or centenarians who have been tested by time and achieved remarkable healthy longevity.This review advocates for delineating 'what defines a healthy microbiome?' by considering a broader range of factors related to human health and environmental influences on the microbiota. A healthy microbiome is undoubtedly linked to gut health. Nevertheless, it is very difficult to pinpoint a universally accepted definition of 'gut health' due to the complexities of measuring gut functionality besides the microbiota composition. We must take into account individual variabilities, the influence of diet, lifestyle, host and environmental factors. Moreover, the challenge in distinguishing causation from correlation between gut microbiome and overall health is presented.The review also highlights the resource-heavy nature of comprehensive gut health assessments, which hinders their practicality and broad application. Finally, we call for continued research and a nuanced approach to better understand the intricate and evolving concept of gut health, emphasising the need for more precise and inclusive definitions and methodologies in studying the microbiome.}, }
@article {pmid39320132, year = {2024}, author = {Bosland, MC and Gordon, T and Solomon, JJ and Shore, RE and Lippmann, M}, title = {Seventy-five years of impactful environmental and occupational health research at the Nelson Institute of Environmental Medicine at New York University.}, journal = {Annals of the New York Academy of Sciences}, volume = {1540}, number = {1}, pages = {147-165}, doi = {10.1111/nyas.15226}, pmid = {39320132}, issn = {1749-6632}, mesh = {Humans ; Academies and Institutes/history ; Biomedical Research/history/trends ; *Environmental Health/history ; *Environmental Medicine/history/trends ; History, 20th Century ; History, 21st Century ; New York ; New York City ; *Occupational Health/history ; Universities/history ; }, abstract = {Founded in 1947 as the Institute of Industrial Medicine, the Nelson Institute and Department of Environmental Medicine at New York University (NYU) Grossman School of Medicine (NYUGSOM) was supported by a National Institute of Environmental Health Science (NIEHS) Center Grant for over 56 years. Nelson Institute researchers generated 75 years of impactful research in environmental and occupational health, radiation effects, toxicology, and cancer. Environmental health research is continuing at NYUGSOM in its departments of medicine and population health. The objective of this historical commentary is to highlight the major achievements of the Nelson Institute and the department in the context of its history at facilities in Sterling Forest, Tuxedo, NY and Manhattan, NY. Aspects of our discussion include leadership, physical facilities, and research in many areas, including air pollution, health effects of environmental radiation exposures, inhalation toxicology methodology, carcinogenesis by chemicals, metals, and hormones, cancer chemoprevention, human microbiome, ecotoxicology, epidemiology, biostatistics, and community health concerns. The research of the institute and department benefited from unique facilities, strong leadership focused on team-based science, and outstanding investigators, students, and staff. A major lasting contribution has been the training of hundreds of graduate students and postdoctoral fellows, many of whom have been and are training the next generation of environmental and occupational health researchers at various institutions.}, }
@article {pmid39315152, year = {2024}, author = {Zheng, B and Xu, J and Zhang, Y and Qin, J and Yuan, D and Fan, T and Wu, W and Chen, Y and Jiang, Y}, title = {MBCN: A novel reference database for Effcient Metagenomic analysis of human gut microbiome.}, journal = {Heliyon}, volume = {10}, number = {18}, pages = {e37422}, pmid = {39315152}, issn = {2405-8440}, abstract = {Metagenomic shotgun sequencing data can identify microbes and their proportions. But metagenomic shotgun data profiling results obtained from multiple projects using different reference databases are difficult to compare and apply meta-analysis. Our work aims to create a novel collection of human gut prokaryotic genomes, named Microbiome Collection Navigator (MBCN). 2379 human gut metagenomic samples are screened, and 16,785 metagenome-assembled genomes (MAGs) are assembled using a standardized pipeline. In addition, MAGs are combined with the representative genomes from public prokaryotic genomes collections to cluster, and pan-genomes for each cluster's genomes are constructed to build Kraken2 and Bracken databases. The databases built by MBCN are more comprehensive and accurate for profiling metagenomic reads comparing with other collections on simulated reads and virtual bio-projects. We profile 1082 human gut metagenomic samples with MBCN database and organize profiles and metadata on the web program. Meanwhile, using MBCN as a reference database, we also develop a unified, standardized, and systematic metagenomic analysis pipeline and platform, named MicrobiotaCN (http://www.microbiota.cn) and common statistical and visualization tools for microbiome research are integrated into the web program. Taken together, MBCN and MicrobiotaCN can be a valuable resource and a powerful tool that allows researchers to perform metagenomic analysis by a unified pipeline efficiently.}, }
@article {pmid39313228, year = {2024}, author = {Kirtipal, N and Seo, Y and Son, J and Lee, S}, title = {Systems Biology of Human Microbiome for the Prediction of Personal Glycaemic Response.}, journal = {Diabetes &amp; metabolism journal}, volume = {48}, number = {5}, pages = {821-836}, pmid = {39313228}, issn = {2233-6087}, support = {//Ministry of Science ICT/ ; 2021R1C1C1006336//National Research Foundation of Korea/ ; 2021M3A9G8022959//National Research Foundation of Korea/ ; RS-2024-00419699//National Research Foundation of Korea/ ; //Korea Health Industry Development Institute/ ; HR22C141105//Ministry of Health and Welfare/ ; 2024-ER2108-00//Korea National Institute of Health/ ; 2024-ER0608-00//Korea National Institute of Health/ ; //GIST Research Institute/ ; }, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Precision Medicine/methods ; *Systems Biology/methods ; Machine Learning ; Dysbiosis ; Blood Glucose/analysis ; Diabetes Mellitus/microbiology ; Diabetes Mellitus, Type 2/microbiology ; Hypoglycemic Agents/therapeutic use ; }, abstract = {The human gut microbiota is increasingly recognized as a pivotal factor in diabetes management, playing a significant role in the body's response to treatment. However, it is important to understand that long-term usage of medicines like metformin and other diabetic treatments can result in problems, gastrointestinal discomfort, and dysbiosis of the gut flora. Advanced sequencing technologies have improved our understanding of the gut microbiome's role in diabetes, uncovering complex interactions between microbial composition and metabolic health. We explore how the gut microbiota affects glucose metabolism and insulin sensitivity by examining a variety of -omics data, including genomics, transcriptomics, epigenomics, proteomics, metabolomics, and metagenomics. Machine learning algorithms and genome-scale modeling are now being applied to find microbiological biomarkers associated with diabetes risk, predicted disease progression, and guide customized therapy. This study holds promise for specialized diabetic therapy. Despite significant advances, some concerns remain unanswered, including understanding the complex relationship between diabetes etiology and gut microbiota, as well as developing user-friendly technological innovations. This mini-review explores the relationship between multiomics, precision medicine, and machine learning to improve our understanding of the gut microbiome's function in diabetes. In the era of precision medicine, the ultimate goal is to improve patient outcomes through personalized treatments.}, }
@article {pmid39307902, year = {2024}, author = {Ma, Z and Zuo, T and Frey, N and Rangrez, AY}, title = {A systematic framework for understanding the microbiome in human health and disease: from basic principles to clinical translation.}, journal = {Signal transduction and targeted therapy}, volume = {9}, number = {1}, pages = {237}, pmid = {39307902}, issn = {2059-3635}, support = {RA 2717/4-1//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; 1289/17-1//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; }, mesh = {Humans ; *Microbiota/genetics ; Probiotics/therapeutic use ; Symbiosis/genetics ; }, abstract = {The human microbiome is a complex and dynamic system that plays important roles in human health and disease. However, there remain limitations and theoretical gaps in our current understanding of the intricate relationship between microbes and humans. In this narrative review, we integrate the knowledge and insights from various fields, including anatomy, physiology, immunology, histology, genetics, and evolution, to propose a systematic framework. It introduces key concepts such as the 'innate and adaptive genomes', which enhance genetic and evolutionary comprehension of the human genome. The 'germ-free syndrome' challenges the traditional 'microbes as pathogens' view, advocating for the necessity of microbes for health. The 'slave tissue' concept underscores the symbiotic intricacies between human tissues and their microbial counterparts, highlighting the dynamic health implications of microbial interactions. 'Acquired microbial immunity' positions the microbiome as an adjunct to human immune systems, providing a rationale for probiotic therapies and prudent antibiotic use. The 'homeostatic reprogramming hypothesis' integrates the microbiome into the internal environment theory, potentially explaining the change in homeostatic indicators post-industrialization. The 'cell-microbe co-ecology model' elucidates the symbiotic regulation affecting cellular balance, while the 'meta-host model' broadens the host definition to include symbiotic microbes. The 'health-illness conversion model' encapsulates the innate and adaptive genomes' interplay and dysbiosis patterns. The aim here is to provide a more focused and coherent understanding of microbiome and highlight future research avenues that could lead to a more effective and efficient healthcare system.}, }
@article {pmid39306588, year = {2024}, author = {Sahin, TK and Sonmezer, MC}, title = {The role of the microbiome in head and neck squamous cell cancers.}, journal = {European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery}, volume = {}, number = {}, pages = {}, pmid = {39306588}, issn = {1434-4726}, abstract = {The human microbiome has garnered tremendous interest in the field of oncology, and microbiota studies in head and neck oncology has also flourished. Given the increasing incidence and mortality of HNSCC, as well as the suboptimal outcomes of available treatments, there is an urgent need for innovative approaches involving the microbiome. This review evaluates the intricate relationship between the microbiome and HNSCC, highlighting the potential of the microbiome as a marker for cancer detection, its role in malignancy, and its impact on the efficacy of conventional treatments like chemotherapy and radiotherapy. The review also explores the effects of treatment modalities on the microbiome and discusses the potential of microbiome alterations to predict and influence treatment toxicities such as mucositis and xerostomia. Further research is warranted to characterize the microbiome-HNSCC association, which holds promise for advancing early diagnosis, enhancing prognostic accuracy, and personalizing treatment strategies to improve patient outcomes. The exploration of the microbiome in clinical trials indicates a burgeoning subject of microbiome-focused therapies, heralding a new frontier in most cancer care.}, }
@article {pmid39304775, year = {2024}, author = {Ray, K}, title = {A resource for the food microbiome and its links with the human microbiome.}, journal = {Nature reviews. Gastroenterology &amp; hepatology}, volume = {21}, number = {11}, pages = {746}, pmid = {39304775}, issn = {1759-5053}, }
@article {pmid39303118, year = {2024}, author = {Doré, J and Sansonetti, PJ}, title = {[The human microbiome: 340 years of history, 140 years of interrogations, technological innovations and emergence of "microbial medicine"].}, journal = {Medecine sciences : M/S}, volume = {40}, number = {8-9}, pages = {654-660}, doi = {10.1051/medsci/2024101}, pmid = {39303118}, issn = {1958-5381}, mesh = {Humans ; Gastrointestinal Microbiome/physiology ; History, 18th Century ; History, 19th Century ; History, 20th Century ; History, 21st Century ; Inventions/history/trends ; *Microbiota/physiology ; Symbiosis ; History, 17th Century ; }, abstract = {For 350 years, we have known that the human body hosts microbes, then called "animalcules". For over a century, following the demonstration of the role of some of these microbes in diseases, questions have arisen about the role of the largely predominant ones colonizing human skin and mucous surfaces, particularly the rich microbial ecosystem of the intestine, the gut microbiota. From the invention of germ-free life - axenism - which experimentally validated the human-microbe symbiosis, resulting from a long coevolution, to the development of anaerobic culture methods, then to the invention of molecular diagnosis, deep sequencing opening up metagenomic and omics approaches in general, a remarkable race has taken place between technological innovations and conceptual advances. This race, beyond the exhaustive description of the microbiota in its intra- and inter-human diversity, and the essential symbiotic functions of the microbiome, has paved the way for a new field of medicine: microbial medicine.}, }
@article {pmid39300165, year = {2024}, author = {Bisht, V and Das, B and Hussain, A and Kumar, V and Navani, NK}, title = {Understanding of probiotic origin antimicrobial peptides: a sustainable approach ensuring food safety.}, journal = {NPJ science of food}, volume = {8}, number = {1}, pages = {67}, pmid = {39300165}, issn = {2396-8370}, abstract = {The practice of preserving and adding value to food dates back to over 10,000 BCE, when unintentional microbial-driven chemical reactions imparted flavor and extended the shelf life of fermented foods. The process evolved, and with the urbanization of society, significant shifts in dietary habits emerged, accompanied by sporadic food poisoning incidents. The repercussions of the COVID-19 pandemic have intensified the search for antibiotic alternatives owing to the rise in antibiotic-resistant pathogens, emphasizing the exploration of probiotic-origin antimicrobial peptides to alleviate human microbiome collateral damage. Often termed 'molecular knives', these peptides outstand as potent antimicrobials due to their compatibility with innate microflora, amenability to bioengineering, target specificity, versatility and rapidity in molecular level mode of action. This review centres on bacteriocins sourced from lactic acid bacteria found in ethnic fermented foods, accentuating their desirable attributes, technological applications as nanobiotics and potential future applications in the modern context of ensuring food safety.}, }
@article {pmid39298326, year = {2024}, author = {Gordon, JI and Barratt, MJ and Hibberd, MC and Rahman, M and Ahmed, T}, title = {Establishing human microbial observatory programs in low- and middle-income countries.}, journal = {Annals of the New York Academy of Sciences}, volume = {1540}, number = {1}, pages = {13-20}, doi = {10.1111/nyas.15224}, pmid = {39298326}, issn = {1749-6632}, support = {//Fondazione Internazionale Premio Balzan/ ; //Bill and Melinda Gates Foundation/ ; /NH/NIH HHS/United States ; /NH/NIH HHS/United States ; }, mesh = {Humans ; *Developing Countries ; Global Health ; *Microbiota ; }, abstract = {Studies of the human microbiome are progressing rapidly but have largely focused on populations living in high-income countries. With increasing evidence that the microbiome contributes to the pathogenesis of diseases that affect infants, children, and adults in low- and middle-income countries (LMICs), and with profound and rapid ongoing changes occurring in our lifestyles and biosphere, understanding the origins of and developing microbiome-directed therapeutics for treating a number of global health challenges requires the development of programs for studying human microbial ecology in LMICs. Here, we discuss how the establishment of long-term human microbial observatory programs in selected LMICs could provide one timely approach.}, }
@article {pmid39292000, year = {2024}, author = {Kilgore, PB and Sha, J and Hendrix, EK and Neil, BH and Lawrence, WS and Peel, JE and Hittle, L and Woolston, J and Sulakvelidze, A and Schwartz, JA and Chopra, AK}, title = {A bacteriophage cocktail targeting Yersinia pestis provides strong post-exposure protection in a rat pneumonic plague model.}, journal = {Microbiology spectrum}, volume = {12}, number = {11}, pages = {e0094224}, pmid = {39292000}, issn = {2165-0497}, support = {T32 AI141349/AI/NIAID NIH HHS/United States ; HHSN272201700040I/AI/NIAID NIH HHS/United States ; T32 AI179595/AI/NIAID NIH HHS/United States ; AI 141349//HHS | National Institutes of Health (NIH)/ ; HHSN272201700040I/75N93022F00003//HHS | National Institutes of Health (NIH)/ ; }, mesh = {Animals ; *Yersinia pestis ; *Plague/prevention &amp; control/microbiology ; Rats ; *Bacteriophages/physiology/genetics ; *Disease Models, Animal ; *Phage Therapy/methods ; Female ; Post-Exposure Prophylaxis/methods ; }, abstract = {Yersinia pestis, one of the deadliest bacterial pathogens ever known, is responsible for three plague pandemics and several epidemics, with over 200 million deaths during recorded history. Due to high genomic plasticity, Y. pestis is amenable to genetic mutations as well as genetic engineering that can lead to the emergence or intentional development of pan-drug-resistant strains. Indeed, antibiotic-resistant strains (e.g., strains carrying multidrug-resistant or MDR plasmids) have been isolated in various countries and endemic areas. Thus, there is an urgent need to develop novel, safe, and effective treatment approaches for managing Y. pestis infections. This includes infections by antigenically distinct strains for which vaccines (none FDA approved yet) may not be effective and those that cannot be managed by currently available antibiotics. Lytic bacteriophages provide one such alternative approach. In this study, we examined post-exposure efficacy of a bacteriophage cocktail, YPP-401, to combat pneumonic plague caused by Y. pestis CO92. YPP-401 is a four-phage preparation effective against a panel of at least 68 genetically diverse Y. pestis strains. Using a pneumonic plague aerosol challenge model in gender-balanced Brown Norway rats, YPP-401 demonstrated ~88% protection when delivered 18 h post-exposure for each of two administration routes (i.e., intraperitoneal and intranasal) in a dose-dependent manner. Our studies provide proof-of-concept that YPP-401 could be an innovative, safe, and effective approach for managing Y. pestis infections, including those caused by naturally occurring or intentionally developed multidrug-resistant strains.IMPORTANCECurrently, there are no FDA-approved plague vaccines. Since antibiotic-resistant strains of Y. pestis have emerged or are being intentionally developed to be used as a biothreat agent, new treatment modalities are direly needed. Phage therapy provides a viable option against potentially antibiotic-resistant strains. Additionally, phages are nontoxic and have been approved by the FDA for use in the food industry. Our study provides the first evidence of the protective effect of a cocktail of four phages against pneumonic plague, the most severe form of disease. When treatment was initiated 18 h post infection by either the intranasal or intraperitoneal route in Brown Norway rats, up to 87.5% protection was observed. The phage cocktail had a minimal impact on a representative human microbiome panel, unlike antibiotics. This study provides strong proof-of-concept data for the further development of phage-based therapy to treat plague.}, }
@article {pmid39283061, year = {2024}, author = {McBurney, MI and Cho, CE}, title = {Understanding the role of the human gut microbiome in overweight and obesity.}, journal = {Annals of the New York Academy of Sciences}, volume = {1540}, number = {1}, pages = {61-88}, doi = {10.1111/nyas.15215}, pmid = {39283061}, issn = {1749-6632}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Obesity/microbiology/metabolism ; *Overweight/microbiology ; Probiotics ; Prebiotics/administration &amp; dosage ; Fecal Microbiota Transplantation ; Diet ; }, abstract = {The gut microbiome may be related to the prevalence of overweight and obesity, but high interindividual variability of the human microbiome complicates our understanding. Obesity often occurs concomitantly with micronutrient deficiencies that impair energy metabolism. Microbiota composition is affected by diet. Host-microbiota interactions are bidirectional. We propose three pathways whereby these interactions may modulate the gut microbiome and obesity: (1) ingested compounds or derivatives affecting small intestinal transit, endogenous secretions, digestion, absorption, microbiome balance, and gut barrier function directly affect host metabolism; (2) substrate availability affecting colonic microbial composition and contact with the gut barrier; and (3) microbial end products affecting host metabolism. The quantity/concentration, duration, and/or frequency (circadian rhythm) of changes in these pathways can alter the gut microbiome, disrupt the gut barrier, alter host immunity, and increase the risk of and progression to overweight and obesity. Host-specific characteristics (e.g., genetic variations) may further affect individual sensitivity and/or resilience to diet- and microbiome-associated perturbations in the colonic environment. In this narrative review, the effects of selected interventions, including fecal microbiota transplantation, dietary calorie restriction, dietary fibers and prebiotics, probiotics and synbiotics, vitamins, minerals, and fatty acids, on the gut microbiome, body weight, and/or adiposity are summarized to help identify mechanisms of action and research opportunities.}, }
@article {pmid39273475, year = {2024}, author = {Larson, J and Sather, B and Wang, L and Westrum, J and Tokmina-Lukaszewska, M and Pauley, J and Copié, V and McDermott, TR and Bothner, B}, title = {Metalloproteomics Reveals Multi-Level Stress Response in Escherichia coli When Exposed to Arsenite.}, journal = {International journal of molecular sciences}, volume = {25}, number = {17}, pages = {}, pmid = {39273475}, issn = {1422-0067}, support = {P42ES031007//University of North Carolina's Superfund Program/ ; DE-SC0020246//U.S. Department of Energy/ ; S10 OD028650/OD/NIH HHS/United States ; MCB 1714556//National Science Foundation/ ; P42 ES031007/ES/NIEHS NIH HHS/United States ; R24 GM137786/GM/NIGMS NIH HHS/United States ; R24GM137786/GM/NIGMS NIH HHS/United States ; P20 GM103474/GM/NIGMS NIH HHS/United States ; }, mesh = {*Arsenites/toxicity ; *Escherichia coli/genetics/metabolism/drug effects ; *Escherichia coli Proteins/genetics/metabolism ; *Proteomics/methods ; *Stress, Physiological ; *Gene Expression Regulation, Bacterial/drug effects ; *Operon/genetics ; Metalloproteins/metabolism/genetics ; Humans ; }, abstract = {The arsRBC operon encodes a three-protein arsenic resistance system. ArsR regulates the transcription of the operon, while ArsB and ArsC are involved in exporting trivalent arsenic and reducing pentavalent arsenic, respectively. Previous research into Agrobacterium tumefaciens 5A has demonstrated that ArsR has regulatory control over a wide range of metal-related proteins and metabolic pathways. We hypothesized that ArsR has broad regulatory control in other Gram-negative bacteria and set out to test this. Here, we use differential proteomics to investigate changes caused by the presence of the arsR gene in human microbiome-relevant Escherichia coli during arsenite (As[III]) exposure. We show that ArsR has broad-ranging impacts such as the expression of TCA cycle enzymes during As[III] stress. Additionally, we found that the Isc [Fe-S] cluster and molybdenum cofactor assembly proteins are upregulated regardless of the presence of ArsR under these same conditions. An important finding from this differential proteomics analysis was the identification of response mechanisms that were strain-, ArsR-, and arsenic-specific, providing new clarity to this complex regulon. Given the widespread occurrence of the arsRBC operon, these findings should have broad applicability across microbial genera, including sensitive environments such as the human gastrointestinal tract.}, }
@article {pmid39271424, year = {2024}, author = {Bokulich, NA and Robeson, MS}, title = {Bioinformatics challenges for profiling the microbiome in cancer: pitfalls and opportunities.}, journal = {Trends in microbiology}, volume = {32}, number = {12}, pages = {1163-1166}, doi = {10.1016/j.tim.2024.08.011}, pmid = {39271424}, issn = {1878-4380}, mesh = {Humans ; *Neoplasms/microbiology ; *Microbiota ; *Computational Biology/methods ; *Metagenomics/methods ; *Machine Learning ; Sequence Analysis, DNA/methods ; }, abstract = {Increasing evidence suggests that the human microbiome plays an important role in cancer risk and treatment. Untargeted 'omics' techniques have accelerated research into microbiome-cancer interactions, supporting the discovery of novel associations and mechanisms. However, these techniques require careful selection and use to avoid biases and other pitfalls. In this essay, we discuss selected challenges involved in the analysis of microbiome data in the context of cancer, including the application of machine learning (ML). We focus on DNA sequencing-based (e.g., metagenomics) methods, but many of the pitfalls and opportunities generalize to other omics technologies as well. We advocate for extended training opportunities, community standards, and best practices for sharing data and code to advance transparency and reproducibility in cancer microbiome research.}, }
@article {pmid39256307, year = {2024}, author = {Rastegar, S and Skurnik, M and Niaz, H and Tadjrobehkar, O and Samareh, A and Hosseini-Nave, H and Sabouri, S}, title = {Isolation, characterization, and potential application of Acinetobacter baumannii phages against extensively drug-resistant strains.}, journal = {Virus genes}, volume = {60}, number = {6}, pages = {725-736}, pmid = {39256307}, issn = {1572-994X}, support = {KMU.AC.IR.400000652//Hossein Hosseini-Nave1/ ; }, mesh = {*Acinetobacter baumannii/virology/drug effects ; *Genome, Viral/genetics ; *Bacteriophages/genetics/isolation &amp; purification/classification/physiology ; *Drug Resistance, Multiple, Bacterial ; *Host Specificity ; *Anti-Bacterial Agents/pharmacology ; Acinetobacter Infections/microbiology ; Phage Therapy ; Sewage/virology/microbiology ; Humans ; }, abstract = {One of the significant issues in treating bacterial infections is the increasing prevalence of extensively drug-resistant (XDR) strains of Acinetobacter baumannii. In the face of limited or no viable treatment options for extensively drug-resistant (XDR) bacteria, there is a renewed interest in utilizing bacteriophages as a treatment option. Three Acinetobacter phages (vB_AbaS_Ftm, vB_AbaS_Eva, and vB_AbaS_Gln) were identified from hospital sewage and analyzed for their morphology, host ranges, and their genome sequences were determined and annotated. These phages and vB_AbaS_SA1 were combined to form a phage cocktail. The antibacterial effects of this cocktail and its combinations with selected antimicrobial agents were evaluated against the XDR A. baumannii strains. The phages exhibited siphovirus morphology. Out of a total of 30 XDR A. baumannii isolates, 33% were sensitive to vB_AbaS_Ftm, 30% to vB_AbaS_Gln, and 16.66% to vB_AbaS_Eva. When these phages were combined with antibiotics, they demonstrated a synergistic effect. The genome sizes of vB_AbaS_Ftm, vB_AbaS_Eva, and vB_AbaS_Gln were 48487, 50174, and 50043 base pairs (bp), respectively, and showed high similarity. Phage cocktail, when combined with antibiotics, showed synergistic effects on extensively drug-resistant (XDR) strains of A. baumannii. However, the need for further study to fully understand the mechanisms of action and potential limitations of using these phages is highlighted.}, }
@article {pmid39256189, year = {2024}, author = {Yılmaz, SS and Kuşkucu, MA and Çakan, H and Aygün, G}, title = {Effective use of skin microbiome signatures for fingerprint identification.}, journal = {Skin research and technology : official journal of International Society for Bioengineering and the Skin (ISBS) [and] International Society for Digital Imaging of Skin (ISDIS) [and] International Society for Skin Imaging (ISSI)}, volume = {30}, number = {9}, pages = {e70052}, pmid = {39256189}, issn = {1600-0846}, support = {28100//Research Fund of Istanbul University-Cerrahpa&#x15f;a/ ; }, mesh = {Humans ; *Microbiota/genetics ; *Skin/microbiology ; Adult ; Male ; Female ; Staphylococcus epidermidis/isolation &amp; purification/genetics ; Ribotyping/methods ; Dermatoglyphics ; RNA, Ribosomal, 16S/genetics ; Young Adult ; Minisatellite Repeats ; }, abstract = {BACKGROUND: Recent advances have increased the importance of the human microbiome, including the skin microbiome. Despite the hand microbiome research, the factors affecting the composition of the hand microbiome and their personal characteristics are incompletely known.<br><br>OBJECTIVES: Despite changing environmental factors and personal variation, we aimed to indicate the interpersonal distinction between skin microbiota using simple and rapid molecular methods.<br><br>METHODS: Over a non-consecutive 10-day period, samples were taken from 10 adult individuals, and ribotyping analysis of the 16S and 23S genes of S. epidermidis was performed on each skin sample. Additionally, EcoRI and HindIII enzyme reactions and variable number tandem repeat (VNTR) reactions of S. epidermidis obtained from DNA samples were performed. The skin microbiomes of individuals were evaluated along with the microbiome profiles left on the surfaces they touched.<br><br>RESULTS: In the environmental samples taken, it has been observed that people preserve their core skin microbiota characters and carry them to their environment. It was determined that the highest similarity rate was 77.14%, and the lowest similarity rate was 31.74%.<br><br>CONCLUSION: Our study showed that the core skin microbiota retains its characteristics and leaves traces in environments. The fact that the personal microbiome remains unchanged despite environmental differences and has characteristic features has shown that it can be used in forensic sciences to distinguish individuals from each other. These results with simple and rapid methods further increased the importance and significance of the study. The findings indicate that personal skin microbiota can provide a significant contribution to criminal investigations by increasing accuracy and reliability, especially in forensic analyses.}, }
@article {pmid39255394, year = {2024}, author = {Ginsberg, SD and Blaser, MJ}, title = {Alzheimer's Disease Has Its Origins in Early Life via a Perturbed Microbiome.}, journal = {The Journal of infectious diseases}, volume = {230}, number = {Supplement_2}, pages = {S141-S149}, pmid = {39255394}, issn = {1537-6613}, support = {//Emch Foundation/ ; //Infectious Diseases Society of America/ ; U01 AI122285/AI/NIAID NIH HHS/United States ; U01 AI122285/NH/NIH HHS/United States ; R01 AG072599/AG/NIA NIH HHS/United States ; //C &amp; D Fund/ ; }, mesh = {Animals ; Humans ; *Alzheimer Disease/microbiology/physiopathology ; Anti-Bacterial Agents/administration &amp; dosage/adverse effects ; Brain/microbiology/pathology/physiopathology ; *Gastrointestinal Microbiome/drug effects/physiology ; Disease Models, Animal ; Brain-Gut Axis/drug effects/physiology ; }, abstract = {Alzheimer's disease (AD) is a neurodegenerative disorder with limited therapeutic options. Accordingly, new approaches for prevention and treatment are needed. One focus is the human microbiome, the consortium of microorganisms that live in and on us, which contributes to human immune, metabolic, and cognitive development and that may have mechanistic roles in neurodegeneration. AD and Alzheimer's disease-related dementias (ADRD) are recognized as spectrum disorders with complex pathobiology. AD/ADRD onset begins before overt clinical signs, but initiation triggers remain undefined. We posit that disruption of the normal gut microbiome in early life leads to a pathological cascade within septohippocampal and cortical brain circuits. We propose investigation to understand how early-life microbiota changes may lead to hallmark AD pathology in established AD/ADRD models. Specifically, we hypothesize that antibiotic exposure in early life leads to exacerbated AD-like disease endophenotypes that may be amenable to specific microbiological interventions. We propose suitable models for testing these hypotheses.}, }
@article {pmid39255040, year = {2024}, author = {Sanches Santos Rizzo Zuttion, M and Parimon, T and Bora, SA and Yao, C and Lagree, K and Gao, CA and Wunderink, RG and Kitsios, GD and Morris, A and Zhang, Y and McVerry, BJ and Modes, ME and Marchevsky, AM and Stripp, BR and Soto, CM and Wang, Y and Merene, K and Cho, S and Victor, BL and Vujkovic-Cvijin, I and Gupta, S and Cassel, SL and Sutterwala, FS and Devkota, S and Underhill, DM and Chen, P}, title = {Antibiotic use during influenza infection augments lung eosinophils that impair immunity against secondary bacterial pneumonia.}, journal = {The Journal of clinical investigation}, volume = {134}, number = {21}, pages = {}, pmid = {39255040}, issn = {1558-8238}, support = {R03 HL162655/HL/NHLBI NIH HHS/United States ; F32 HL162377/HL/NHLBI NIH HHS/United States ; K23 HL169815/HL/NHLBI NIH HHS/United States ; U19 AI135964/AI/NIAID NIH HHS/United States ; P01 HL154998/HL/NHLBI NIH HHS/United States ; U01 TR003528/TR/NCATS NIH HHS/United States ; UL1 TR001881/TR/NCATS NIH HHS/United States ; R01 HL164177/HL/NHLBI NIH HHS/United States ; R01 HL159953/HL/NHLBI NIH HHS/United States ; P01 HL114453/HL/NHLBI NIH HHS/United States ; R01 LM013337/LM/NLM NIH HHS/United States ; R01 HL155759/HL/NHLBI NIH HHS/United States ; R01 HL163646/HL/NHLBI NIH HHS/United States ; }, mesh = {Animals ; Mice ; *Eosinophils/immunology ; Humans ; *Anti-Bacterial Agents/pharmacology ; *Methicillin-Resistant Staphylococcus aureus/immunology ; *Lung/immunology/pathology ; *Influenza, Human/immunology/drug therapy ; Female ; *Orthomyxoviridae Infections/immunology/drug therapy ; Male ; Pneumonia, Bacterial/immunology/drug therapy ; Pneumonia, Staphylococcal/immunology/drug therapy ; }, abstract = {A leading cause of mortality after influenza infection is the development of a secondary bacterial pneumonia. In the absence of a bacterial superinfection, prescribing antibacterial therapies is not indicated but has become a common clinical practice for those presenting with a respiratory viral illness. In a murine model, we found that antibiotic use during influenza infection impaired the lung innate immunologic defenses toward a secondary challenge with methicillin-resistant Staphylococcus aureus (MRSA). Antibiotics augment lung eosinophils, which have inhibitory effects on macrophage function through the release of major basic protein. Moreover, we demonstrated that antibiotic treatment during influenza infection caused a fungal dysbiosis that drove lung eosinophilia and impaired MRSA clearance. Finally, we evaluated 3 cohorts of hospitalized patients and found that eosinophils positively correlated with antibiotic use, systemic inflammation, and worsened outcomes. Altogether, our work demonstrates a detrimental effect of antibiotic treatment during influenza infection that has harmful immunologic consequences via recruitment of eosinophils to the lungs, thereby increasing the risk of developing a secondary bacterial infection.}, }
@article {pmid39254049, year = {2024}, author = {Harris, RM and Pace, F and Kuntz, TM and Morgan, XC and Hyland, P and Summers, K and McDermott, E and Blumen, K and Watnick, PI}, title = {Testosterone treatment impacts the intestinal microbiome of transgender individuals.}, journal = {mSphere}, volume = {9}, number = {10}, pages = {e0055724}, pmid = {39254049}, issn = {2379-5042}, mesh = {Humans ; *Gastrointestinal Microbiome/drug effects ; *Testosterone ; Male ; *Transgender Persons ; Female ; Pilot Projects ; *Feces/microbiology ; Adult ; Metagenomics ; Middle Aged ; Glutamic Acid/metabolism ; Bacteria/classification/genetics/drug effects/metabolism/isolation &amp; purification ; }, abstract = {Medical modulation of sex hormone levels is a cornerstone of treatment for many conditions that impact well-being, including cancer, fertility/infertility, gender dysphoria, and chronic metabolic diseases such as diabetes and obesity. The microbial residents of the intestine, known as the microbiota, interact with sex hormones in the intestine, and there is correlative evidence that this interaction is bidirectional. Based on these published findings, we hypothesized that transgender individuals receiving exogenous testosterone as part of their gender-affirming medical treatment might undergo changes in their intestinal microbiome. To test this, we collected 26 stool samples from nine individuals before and up to 8 months after initiation of treatment with exogenous testosterone and subjected these samples to metagenomic analysis. While no species were significantly associated with the duration of testosterone therapy, pathways that generate glutamate increased in abundance, while those that consume glutamate decreased. Glutamate is a precursor of arginine, and testosterone is known to increase levels of arginine and its metabolites in the plasma. We hypothesize that testosterone increases the uptake of glutamate by enterocytes, thus decreasing access of the microbiota to this amino acid. While this pilot study establishes the impact of testosterone therapy on the intestinal microbiome, a more comprehensive study is necessary to establish the impact of testosterone-driven metagenomic shifts on the stool metatranscriptome, the stool metabolome, and the plasma metabolome.IMPORTANCEThe human intestine is inhabited by a large community of microbes known as the microbiome. Members of the microbiome consume the diet along with their human host. Thus, the metabolomes of the host and microbe are intricately linked. Testosterone alters the plasma metabolome. In particular, plasma levels of arginine and its metabolites and testosterone are positively correlated. To investigate the impact of exogenous testosterone on the microbiome, we analyzed the stool metagenomes of transgender individuals before and after the initiation of testosterone treatment. In this pilot project, we found a modest impact on the microbiome community structure but an increase in the abundance of metabolic pathways that generate glutamate and spare glutamate consumption. We propose that the host uses glutamate to generate arginine, decreasing the amount available for the microbiome.}, }
@article {pmid39251326, year = {2025}, author = {Zhou, Q and Lei, L and Cheng, J and Chen, J and Du, Y and Zhang, X and Li, Q and Li, C and Deng, H and Wong, CC and Zhuang, B and Li, G and Bai, X}, title = {Microbiota-induced S100A11-RAGE axis underlies immune evasion in right-sided colon adenomas and is a therapeutic target to boost anti-PD1 efficacy.}, journal = {Gut}, volume = {74}, number = {2}, pages = {214-228}, doi = {10.1136/gutjnl-2024-332193}, pmid = {39251326}, issn = {1468-3288}, mesh = {Animals ; *Colonic Neoplasms/immunology/pathology/metabolism/microbiology ; Mice ; *Adenoma/immunology/metabolism/pathology/microbiology ; *Gastrointestinal Microbiome ; *Receptor for Advanced Glycation End Products/metabolism ; Humans ; Immune Evasion ; Immune Checkpoint Inhibitors/pharmacology/therapeutic use ; Programmed Cell Death 1 Receptor/metabolism/antagonists &amp; inhibitors ; Goblet Cells/metabolism/pathology/immunology ; Tumor Escape/immunology ; }, abstract = {BACKGROUND: Tumourigenesis in right-sided and left-sided colons demonstrated distinct features.<br><br>OBJECTIVE: We aimed to characterise the differences between the left-sided and right-sided adenomas (ADs) representing the early stage of colonic tumourigenesis.<br><br>DESIGN: Single-cell and spatial transcriptomic datasets were analysed to reveal alterations between right-sided and left-sided colon ADs. Cells, animal experiments and clinical specimens were used to verify the results.<br><br>RESULTS: Single-cell analysis revealed that in right-sided ADs, there was a significant reduction of goblet cells, and these goblet cells were dysfunctional with attenuated mucin biosynthesis and defective antigen presentation. An impairment of the mucus barrier led to biofilm formation in crypts and subsequent bacteria invasion into right-sided ADs. The regions spatially surrounding the crypts with biofilm occupation underwent an inflammatory response by lipopolysaccharide (LPS) and an apoptosis process, as revealed by spatial transcriptomics. A distinct S100A11[+] epithelial cell population in the right-sided ADs was identified, and its expression level was induced by bacterial LPS and peptidoglycan. S100A11 expression facilitated tumour growth in syngeneic immunocompetent mice with increased myeloid-derived suppressor cells (MDSC) but reduced cytotoxic CD8+ T cells. Targeting S100A11 with well-tolerated antagonists of its receptor for advanced glycation end product (RAGE) (Azeliragon) significantly impaired tumour growth and MDSC infiltration, thereby boosting the efficacy of anti-programmed cell death protein 1 therapy in colon cancer.<br><br>CONCLUSION: Our findings unravelled that dysfunctional goblet cells and consequential bacterial translocation activated the S100A11-RAGE axis in right-sided colon ADs, which recruits MDSCs to promote immune evasion. Targeting this axis by Azeliragon improves the efficacy of immunotherapy in colon cancer.}, }
@article {pmid39244168, year = {2025}, author = {Govender, P and Ghai, M}, title = {Population-specific differences in the human microbiome: Factors defining the diversity.}, journal = {Gene}, volume = {933}, number = {}, pages = {148923}, doi = {10.1016/j.gene.2024.148923}, pmid = {39244168}, issn = {1879-0038}, mesh = {Humans ; Asian People ; Bacteria/genetics/classification ; Bacteriophages/genetics ; Dysbiosis/microbiology ; *Gastrointestinal Microbiome ; *Microbiota ; White People ; Black People ; }, abstract = {Differences in microbial communities at different body habitats define the microbiome composition of the human body. The gut, oral, skin vaginal fluid and tissue microbiome, are pivotal for human development and immune response and cross talk between these microbiomes is evident. Population studies reveal that various factors, such as host genetics, diet, lifestyle, aging, and geographical location are strongly associated with population-specific microbiome differences. The present review discusses the factors that shape microbiome diversity in humans, and microbiome differences in African, Asian and Caucasian populations. Gut microbiome studies show that microbial species Bacteroides is commonly found in individuals living in Western countries (Caucasian populations), while Prevotella is prevalent in non-Western countries (African and Asian populations). This association is mainly due to the high carbohydrate, high fat diet in western countries in contrast to high fibre, low fat diets in African/ Asian regions. Majority of the microbiome studies focus on the bacteriome component; however, interesting findings reveal that increased bacteriophage richness, which makes up the virome component, correlates with decreased bacterial diversity, and causes microbiome dysbiosis. An increase of Caudovirales (bacteriophages) is associated with a decrease in enteric bacteria in inflammatory bowel diseases. Future microbiome studies should evaluate the interrelation between bacteriome and virome to fully understand their significance in the pathogenesis and progression of human diseases. With ethnic health disparities becoming increasingly apparent, studies need to emphasize on the association of population-specific microbiome differences and human diseases, to develop microbiome-based therapeutics. Additionally, targeted phage therapy is emerging as an attractive alternative to antibiotics for bacterial infections. With rapid rise in microbiome research, focus should be on standardizing protocols, advanced bioinformatics tools, and reducing sequencing platform related biases. Ultimately, integration of multi-omics data (genomics, transcriptomics, proteomics and metabolomics) will lead to precision models for personalized microbiome therapeutics advancement.}, }
@article {pmid39243797, year = {2024}, author = {Rodriguez, J and Hassani, Z and Alves Costa Silva, C and Betsou, F and Carraturo, F and Fasano, A and Israelsen, M and Iyappan, A and Krag, A and Metwaly, A and Schierwagen, R and Trebicka, J and Zwart, H and Doré, J and Cordaillat-Simmons, M and Druart, C and , }, title = {State of the art and the future of microbiome-based biomarkers: a multidisciplinary Delphi consensus.}, journal = {The Lancet. Microbe}, volume = {}, number = {}, pages = {100948}, doi = {10.1016/j.lanmic.2024.07.011}, pmid = {39243797}, issn = {2666-5247}, abstract = {Although microbiome signatures have been identified in various contexts (ie, pathogenesis of non-communicable diseases and treatment response), qualified microbiome-based biomarkers are currently not in use in clinical practice. The Human Microbiome Action consortium initiated a Delphi survey to establish a consensus on the needs, challenges, and limitations in developing qualified microbiome-based biomarkers. The questionnaire was developed by a scientific committee via literature review and expert interviews. To ensure broad applicability of the results, 307 experts were invited to participate; 114 of them responded to the first round of the survey, 93 of whom completed the second and final round as well. The survey highlighted the experts' confidence in the potential of microbiome-based biomarkers for several indications or pathologies. The paucity of validated analytical methods appears to be the principal factor hindering the qualification of these biomarkers. The survey also showed that clinical implementation of these biomarkers would only be possible if kitted and validated molecular assays with simple interpretation are developed. This initiative serves as a foundation for designing and implementing public-private collaborative projects to overcome the challenges and promote clinical application of microbiome-based biomarkers.}, }
@article {pmid39240756, year = {2024}, author = {Torrillo, PA and Lieberman, TD}, title = {Reversions mask the contribution of adaptive evolution in microbiomes.}, journal = {eLife}, volume = {13}, number = {}, pages = {}, pmid = {39240756}, issn = {2050-084X}, support = {DP2 GM140922/GM/NIGMS NIH HHS/United States ; 1DP2GM140922-01/NH/NIH HHS/United States ; Graduate Research Fellowship Program//National Science Foundation/ ; }, mesh = {*Mutation ; *Evolution, Molecular ; Selection, Genetic ; Genome, Bacterial ; Microbiota/genetics ; Gastrointestinal Microbiome/genetics ; Bacteroides/genetics ; Adaptation, Physiological/genetics ; Models, Genetic ; Bacteria/genetics/classification ; }, abstract = {When examining bacterial genomes for evidence of past selection, the results depend heavily on the mutational distance between chosen genomes. Even within a bacterial species, genomes separated by larger mutational distances exhibit stronger evidence of purifying selection as assessed by dN/dS, the normalized ratio of nonsynonymous to synonymous mutations. Here, we show that the classical interpretation of this scale dependence, weak purifying selection, leads to problematic mutation accumulation when applied to available gut microbiome data. We propose an alternative, adaptive reversion model with opposite implications for dynamical intuition and applications of dN/dS. Reversions that occur and sweep within-host populations are nearly guaranteed in microbiomes due to large population sizes, short generation times, and variable environments. Using analytical and simulation approaches, we show that adaptive reversion can explain the dN/dS decay given only dozens of locally fluctuating selective pressures, which is realistic in the context of Bacteroides genomes. The success of the adaptive reversion model argues for interpreting low values of dN/dS obtained from long timescales with caution as they may emerge even when adaptive sweeps are frequent. Our work thus inverts the interpretation of an old observation in bacterial evolution, illustrates the potential of mutational reversions to shape genomic landscapes over time, and highlights the importance of studying bacterial genomic evolution on short timescales.}, }
@article {pmid39238383, year = {2024}, author = {Sanyal, S and Nigam, K and Singh, S and Lohani, P and Dwivedi, M}, title = {Pathophysiological and Clinical Potential of Human Microbiome: Microbe-based Therapeutic Insights.}, journal = {Current pharmaceutical biotechnology}, volume = {}, number = {}, pages = {}, doi = {10.2174/0113892010314433240823113111}, pmid = {39238383}, issn = {1873-4316}, abstract = {The human microbiota represents the community and diverse population of microbes within the human body, which comprises approximately 100 trillion micro-organisms. They exist in the human gastrointestinal tract and various other organs and are now considered virtual body organs. It is mainly represented by bacteria but also includes viruses, fungi, and protozoa. Although there is a heritable component to the gut microbiota, environmental factors related to diet, drugs, and anthropometry determine the composition of the microbiota. Besides the gastrointestinal tract, the human body also harbours microbial communities in the skin, oral and nasal cavities, and reproductive tract. The current review demonstrates the role of gut microbiota and its involvement in processing food, drugs, and immune responses. The discussion focuses on the implications of human microbiota in developing several diseases, such as gastrointestinal infections, metabolic disorders, malignancies, etc., through symbiotic relationships. The microbial population may vary depending on the pathophysiological condition of an individual and thus may be exploited as a therapeutic and clinical player. Further, we need a more thorough investigation to establish the correlation between microbes and pathophysiology in humans and propose them as potential therapeutic targets.}, }
@article {pmid39235252, year = {2024}, author = {Sweet, P and Burroughs, M and Jang, S and Contreras, L}, title = {TolRad, a model for predicting radiation tolerance using Pfam annotations, identifies novel radiosensitive bacterial species from reference genomes and MAGs.}, journal = {Microbiology spectrum}, volume = {12}, number = {10}, pages = {e0383823}, pmid = {39235252}, issn = {2165-0497}, support = {HDTRA1-17-1-0025//DOD | Defense Threat Reduction Agency (DTRA)/ ; FA9550-20-1-0131//DOD | USAF | AMC | Air Force Office of Scientific Research (AFOSR)/ ; W911NF22S0002//DNI | Intelligence Advanced Research Projects Activity (IARPA)/ ; }, mesh = {*Radiation Tolerance/genetics ; *Bacteria/genetics/radiation effects/classification ; *Genome, Bacterial ; Humans ; Radiation, Ionizing ; Bacterial Proteins/genetics/metabolism ; Microbiota/genetics/radiation effects ; Proteome ; Metagenome ; Molecular Sequence Annotation ; }, abstract = {UNLABELLED: The trait of ionizing radiation (IR) tolerance is variable between bacterium, with species succumbing to acute doses as low as 60 Gy and extremophiles able to survive doses exceeding 10,000 Gy. While survival screens have identified multiple highly radioresistant bacteria, such systemic searches have not been conducted for IR-sensitive bacteria. The taxonomy-level diversity of IR sensitivity is poorly understood, as are genetic elements that influence IR sensitivity. Using the protein domain (Pfam) frequencies from 61 bacterial species with experimentally determined D10 values (the dose at which only 10% of the population survives), we trained TolRad, a random forest binary classifier, to distinguish between radiosensitive (D10 < 200 Gy) and radiation-tolerant (D10 > 200 Gy) bacteria. On untrained species, TolRad had an accuracy of 0.900. We applied TolRad to 152 UniProt-hosted bacterial proteomes associated with the human microbiome, including 37 strains from the ATCC Human Microbiome Collection, and classified 34 species as radiosensitive. Whereas IR-sensitive species (D10 < 200 Gy) in the training data set had been confined to the phylum Proteobacterium, this initial TolRad screen identified radiosensitive bacteria in two additional phyla. We experimentally validated the predicted radiosensitivity of a Bacteroidota species from the human microbiome. To demonstrate that TolRad can be applied to metagenome-assembled genomes (MAGs), we tested the accuracy of TolRad on Egg-NOG assembled proteomes (0.965) and partial proteomes. Finally, three collections of MAGs were screened using TolRad, identifying further phyla with radiosensitive species and suggesting that environmental conditions influence the abundance of radiosensitive bacteria.<br><br>IMPORTANCE: Bacterial species have vast genetic diversity, allowing for life in extreme environments and the conduction of complex chemistry. The ability to harness the full potential of bacterial diversity is hampered by the lack of high-throughput experimental or bioinformatic methods for characterizing bacterial traits. Here, we present a computational model that uses de novo-generated genome annotations to classify a bacterium as tolerant of ionizing radiation (IR) or as radiosensitive. This model allows for rapid screening of bacterial communities for low-tolerance species that are of interest for both mechanistic studies into bacterial sensitivity to IR and biomarkers of IR exposure.}, }
@article {pmid39233526, year = {2024}, author = {Kim, TH and Cho, BK and Lee, DH}, title = {Synthetic Biology-Driven Microbial Therapeutics for Disease Treatment.}, journal = {Journal of microbiology and biotechnology}, volume = {34}, number = {10}, pages = {1947-1958}, pmid = {39233526}, issn = {1738-8872}, mesh = {*Synthetic Biology/methods ; Humans ; Animals ; *Gastrointestinal Microbiome ; Metabolic Diseases/therapy/microbiology ; Gastrointestinal Diseases/therapy/microbiology ; Neoplasms/therapy/microbiology ; Biosensing Techniques ; Biological Therapy/methods ; Bacteria/genetics/metabolism ; }, abstract = {The human microbiome, consisting of microorganisms that coexist symbiotically with the body, impacts health from birth. Alterations in gut microbiota driven by factors such as diet and medication can contribute to diseases beyond the gut. Synthetic biology has paved the way for engineered microbial therapeutics, presenting promising treatments for a variety of conditions. Using genetically encoded biosensors and dynamic regulatory tools, engineered microbes can produce and deliver therapeutic agents, detect biomarkers, and manage diseases. This review organizes engineered microbial therapeutics by disease type, emphasizing innovative strategies and recent advancements. The scope of diseases includes gastrointestinal disorders, cancers, metabolic diseases, infections, and other ailments. Synthetic biology facilitates precise targeting and regulation, improving the efficacy and safety of these therapies. With promising results in animal models, engineered microbial therapeutics provide a novel alternative to traditional treatments, heralding a transformative era in diagnostics and treatment for numerous diseases.}, }
@article {pmid39232070, year = {2024}, author = {Jang, H and Koh, H}, title = {A unified web cloud computing platform MiMedSurv for microbiome causal mediation analysis with survival responses.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {20650}, pmid = {39232070}, issn = {2045-2322}, support = {2021R1C1C1013861//National Research Foundation of Korea/ ; }, mesh = {Humans ; *Microbiota ; *Cloud Computing ; *Internet ; Software ; Survival Analysis ; }, abstract = {In human microbiome studies, mediation analysis has recently been spotlighted as a practical and powerful analytic tool to survey the causal roles of the microbiome as a mediator to explain the observed relationships between a medical treatment/environmental exposure and a human disease. We also note that, in a clinical research, investigators often trace disease progression sequentially in time; as such, time-to-event (e.g., time-to-disease, time-to-cure) responses, known as survival responses, are prevalent as a surrogate variable for human health or disease. In this paper, we introduce a web cloud computing platform, named as microbiome mediation analysis with survival responses (MiMedSurv), for comprehensive microbiome mediation analysis with survival responses on user-friendly web environments. MiMedSurv is an extension of our prior web cloud computing platform, named as microbiome mediation analysis (MiMed), for survival responses. The two main features that are well-distinguished are as follows. First, MiMedSurv conducts some baseline exploratory non-mediational survival analysis, not involving microbiome, to survey the disparity in survival response between medical treatments/environmental exposures. Then, MiMedSurv identifies the mediating roles of the microbiome in various aspects: (i) as a microbial ecosystem using ecological indices (e.g., alpha and beta diversity indices) and (ii) as individual microbial taxa in various hierarchies (e.g., phyla, classes, orders, families, genera, species). To illustrate its use, we survey the mediating roles of the gut microbiome between antibiotic treatment and time-to-type 1 diabetes. MiMedSurv is freely available on our web server (http://mimedsurv.micloud.kr).}, }
@article {pmid39230701, year = {2024}, author = {Hera, MR and Liu, S and Wei, W and Rodriguez, JS and Ma, C and Koslicki, D}, title = {Metagenomic functional profiling: to sketch or not to sketch?.}, journal = {Bioinformatics (Oxford, England)}, volume = {40}, number = {Suppl 2}, pages = {ii165-ii173}, pmid = {39230701}, issn = {1367-4811}, support = {R01 GM146462/GM/NIGMS NIH HHS/United States ; R01GM146462/GF/NIH HHS/United States ; }, mesh = {*Metagenomics/methods ; *Software ; *Algorithms ; *Metagenome/genetics ; Humans ; Microbiota/genetics ; Databases, Genetic ; }, abstract = {MOTIVATION: Functional profiling of metagenomic samples is essential to decipher the functional capabilities of microbial communities. Traditional and more widely used functional profilers in the context of metagenomics rely on aligning reads against a known reference database. However, aligning sequencing reads against a large and fast-growing database is computationally expensive. In general, k-mer-based sketching techniques have been successfully used in metagenomics to address this bottleneck, notably in taxonomic profiling. In this work, we describe leveraging FracMinHash (implemented in sourmash, a publicly available software), a k-mer-sketching algorithm, to obtain functional profiles of metagenome samples.<br><br>RESULTS: We show how pieces of the sourmash software (and the resulting FracMinHash sketches) can be put together in a pipeline to functionally profile a metagenomic sample. We named our pipeline fmh-funprofiler. We report that the functional profiles obtained using this pipeline demonstrate comparable completeness and better purity compared to the profiles obtained using other alignment-based methods when applied to simulated metagenomic data. We also report that fmh-funprofiler is 39-99&#xd7; faster in wall-clock time, and consumes up to 40-55&#xd7; less memory. Coupled with the KEGG database, this method not only replicates fundamental biological insights but also highlights novel signals from the Human Microbiome Project datasets.<br><br>This fast and lightweight metagenomic functional profiler is freely available and can be accessed here: https://github.com/KoslickiLab/fmh-funprofiler. All scripts of the analyses we present in this manuscript can be found on GitHub.}, }
@article {pmid39230353, year = {2024}, author = {Bland, CM and Love, BL and Jones, BM}, title = {Human microbiome: Impact of newly approved treatments on C. difficile infection.}, journal = {American journal of health-system pharmacy : AJHP : official journal of the American Society of Health-System Pharmacists}, volume = {}, number = {}, pages = {}, doi = {10.1093/ajhp/zxae249}, pmid = {39230353}, issn = {1535-2900}, abstract = {DISCLAIMER: In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time.<br><br>PURPOSE: The primary purposes of this review are to provide a brief overview of the microbiome, discuss the most relevant outcome data and key characteristics of each live microbiome agent, and pose questions for consideration going forward as these agents are integrated into clinical practice.<br><br>SUMMARY: The management of Clostridiodes difficile infection (CDI) remains a difficult clinical conundrum, with recurrent CDI occurring in 15% to 35% of patients and causing significant morbidity and decreased quality of life. For patients with frequent CDI recurrences, fecal microbiota transplantation (FMT) has been demonstrated to have significant benefit but also significant risks, and FMT is not approved by the US Food and Drug Administration (FDA) for that indication. FDA has established a new therapeutic class for agents known as live biotherapeutic products (LBPs) that offer significant advantages over FMT, including standardized screening, testing, and manufacturing as well as known quantities of organisms contained within. Two new live microbiome products within this class were recently approved by FDA for prevention of CDI recurrences in adult patients following treatment for recurrent CDI with standard antimicrobial therapy. Both agents had demonstrated efficacy in registry trials in preventing CDI recurrence but differ significantly in a number of characteristics, such as route of administration. Cost as well as logistics are current obstacles to use of these therapies.<br><br>CONCLUSION: Live microbiome therapy is a promising solution for patients with recurrent CDI. Future studies should provide further evidence within yet-to-be-evaluated populations not included in registry studies. This along with real-world evidence will inform future use and clinical guideline placement.}, }
@article {pmid39230261, year = {2024}, author = {Tu, V and Ren, Y and Tanes, C and Mukhopadhyay, S and Daniel, SG and Li, H and Bittinger, K}, title = {A quantitative approach to measure and predict microbiome response to antibiotics.}, journal = {mSphere}, volume = {9}, number = {9}, pages = {e0048824}, pmid = {39230261}, issn = {2379-5042}, support = {SAP # 4100068710//Pennsylvania Department of Health (PA DOH)/ ; //Children's Hospital of Philadelphia (CHOP)/ ; }, mesh = {Humans ; *Anti-Bacterial Agents/pharmacology ; *Microbiota/drug effects/genetics ; *RNA, Ribosomal, 16S/genetics ; *Bacteria/drug effects/genetics/classification ; Gastrointestinal Microbiome/drug effects/genetics ; Metagenomics/methods ; Microbial Sensitivity Tests/methods ; Skin/microbiology ; Mouth/microbiology ; Software ; }, abstract = {UNLABELLED: Although antibiotics induce sizable perturbations in the human microbiome, we lack a systematic and quantitative method to measure and predict the microbiome's response to specific antibiotics. Here, we introduce such a method, which takes the form of a microbiome response index (MiRIx) for each antibiotic. Antibiotic-specific MiRIx values quantify the overall susceptibility of the microbiota to an antibiotic, based on databases of bacterial phenotypes and published data on intrinsic antibiotic susceptibility. We applied our approach to five published microbiome studies that carried out antibiotic interventions with vancomycin, metronidazole, ciprofloxacin, amoxicillin, and doxycycline. We show how MiRIx can be used in conjunction with existing microbiome analytical approaches to gain a deeper understanding of the microbiome response to antibiotics. Finally, we generate antibiotic response predictions for the oral, skin, and gut microbiome in healthy humans. Our approach is implemented as open-source software and is readily applied to microbiome data sets generated by 16S rRNA marker gene sequencing or shotgun metagenomics.<br><br>IMPORTANCE: Antibiotics are potent influencers of the human microbiome and can be a source for enduring dysbiosis and antibiotic resistance in healthcare. Existing microbiome data analysis methods can quantify perturbations of bacterial communities but cannot evaluate whether the differences are aligned with the expected activity of a specific antibiotic. Here, we present a novel method to quantify and predict antibiotic-specific microbiome changes, implemented in a ready-to-use software package. This has the potential to be a critical tool to broaden our understanding of the relationship between the microbiome and antibiotics.}, }
@article {pmid39227641, year = {2024}, author = {Donnelly, SC and Varela-Mattatall, GE and Hassan, S and Sun, Q and Gelman, N and Thiessen, JD and Thompson, RT and Prato, FS and Burton, JP and Goldhawk, DE}, title = {Bacterial association with metals enables in vivo monitoring of urogenital microbiota using magnetic resonance imaging.}, journal = {Communications biology}, volume = {7}, number = {1}, pages = {1079}, pmid = {39227641}, issn = {2399-3642}, support = {ALLRP576699-22//Gouvernement du Canada | Natural Sciences and Engineering Research Council of Canada (Conseil de Recherches en Sciences Naturelles et en G&#xe9;nie du Canada)/ ; }, mesh = {Humans ; *Magnetic Resonance Imaging/methods ; *Microbiota ; Female ; Bacteria/metabolism/isolation &amp; purification ; Metals/metabolism ; Urogenital System/microbiology ; Manganese/metabolism/analysis ; }, abstract = {Bacteria constitute a significant part of the biomass of the human microbiota, but their interactions are complex and difficult to replicate outside the host. Exploiting the superior resolution of magnetic resonance imaging (MRI) to examine signal parameters of selected human isolates may allow tracking of their dispersion throughout the body. Here we investigate longitudinal and transverse MRI relaxation rates and found significant differences between several bacterial strains. Common commensal strains of lactobacilli display notably high MRI relaxation rates, partially explained by elevated cellular manganese content, while other species contain more iron than manganese. Lactobacillus crispatus show particularly high values, 4-fold greater than any other species; up to 60-fold greater signal than relevant tissue background; and a linear relationship between relaxation rate and fraction of live cells. Different bacterial strains have detectable, repeatable MRI relaxation rates that in the future may enable monitoring of their persistence in the human body for enhanced molecular imaging.}, }
@article {pmid39226354, year = {2024}, author = {Chimileski, S and Borisy, GG and Dewhirst, FE and Mark Welch, JL}, title = {Tip extension and simultaneous multiple fission in a filamentous bacterium.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {121}, number = {37}, pages = {e2408654121}, pmid = {39226354}, issn = {1091-6490}, support = {R01 DE022586/DE/NIDCR NIH HHS/United States ; DE022586//HHS | NIH | National Institute of Dental and Craniofacial Research (NIDCR)/ ; 2245229//NSF | ENG | Division of Emerging Frontiers and Multidisciplinary Activities (EFMA)/ ; }, mesh = {*Peptidoglycan/metabolism ; Corynebacterium/metabolism/growth &amp; development ; Biofilms/growth &amp; development ; Cell Division ; Humans ; Dental Plaque/microbiology ; }, abstract = {Organisms display an immense variety of shapes, sizes, and reproductive strategies. At microscopic scales, bacterial cell morphology and growth dynamics are adaptive traits that influence the spatial organization of microbial communities. In one such community-the human dental plaque biofilm-a network of filamentous Corynebacterium matruchotii cells forms the core of bacterial consortia known as hedgehogs, but the processes that generate these structures are unclear. Here, using live-cell time-lapse microscopy and fluorescent D-amino acids to track peptidoglycan biosynthesis, we report an extraordinary example of simultaneous multiple division within the domain Bacteria. We show that C. matruchotii cells elongate at one pole through tip extension, similar to the growth strategy of soil-dwelling Streptomyces bacteria. Filaments elongate rapidly, at rates more than five times greater than other closely related bacterial species. Following elongation, many septa form simultaneously, and each cell divides into 3 to 14 daughter cells, depending on the length of the mother filament. The daughter cells then nucleate outgrowth of new thinner vegetative filaments, generating the classic "whip handle" morphology of this taxon. Our results expand the known diversity of bacterial cell cycles and help explain how this filamentous bacterium can compete for space, access nutrients, and form important interspecies interactions within dental plaque.}, }
@article {pmid39221598, year = {2024}, author = {Divakara, N and Dempsey, Z and Saraswati, C and Garssen, J and Silva, D and Keelan, JA and Christophersen, CT and Cooper, MN and Prescott, SL and Palmer, DJ and Verhasselt, V and Macchiaverni, P}, title = {Effect of maternal prebiotic supplementation on human milk immunological composition: Insights from the SYMBA study.}, journal = {Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology}, volume = {35}, number = {9}, pages = {e14226}, doi = {10.1111/pai.14226}, pmid = {39221598}, issn = {1399-3038}, support = {RA/1/3027/386//WA Child Research Fund (WACRF)/ ; //Family Larsson-Rosenquist Foundation/ ; //National Health and Medical Research Council/ ; //Telethon Kids Institute Ascend Fellowship/ ; //Telethon-Perth Children's Hospital Research Fund/ ; //Paul Ramsay Foundation/ ; //Commonwealth Government of Australia/ ; //NHMRC Medical Research Future Fund (MRFF)/ ; }, mesh = {Humans ; *Milk, Human/immunology/chemistry ; *Prebiotics/administration &amp; dosage ; Female ; Double-Blind Method ; *Dietary Supplements ; Pregnancy ; Infant ; Adult ; Male ; Lactation/immunology ; Oligosaccharides/administration &amp; dosage ; Infant, Newborn ; Breast Feeding ; Cytokines/metabolism ; }, abstract = {BACKGROUND: Immunomodulatory proteins in human milk (HM) can shape infant immune development. However, strategies to modulate their levels are currently unknown. This study investigated whether maternal prebiotic supplementation alters the levels of immunomodulatory proteins in HM.<br><br>METHODS: The study was nested within the SYMBA double-blind randomized controlled trial (ACTRN12615001075572), which investigated the effects of maternal prebiotic (short-chain galacto-oligosaccharides/long-chain fructo-oligosaccharides) supplementation from <21&#x2009;weeks gestation during pregnancy until 6 months postnatal during lactation on child allergic disease risk. Mother-child dyads receiving prebiotics (n&#x2009;=&#x2009;46) or placebo (n&#x2009;=&#x2009;54) were included in this study. We measured the levels of 24 immunomodulatory proteins in HM collected at 2, 4, and 6&#x2009;months.<br><br>RESULTS: Cluster analysis showed that the overall immunomodulatory protein composition of milk samples from both groups was similar. At 2&#x2009;months, HM of prebiotic-supplemented women had decreased levels of TGF-&#x3b2;1 and TSLP (95% CI: -17.4 [-29.68, -2.28] and -57.32 [-94.22, -4.7] respectively) and increased levels of sCD14 (95% CI: 1.81 [0.17, 3.71]), when compared to the placebo group. At 4&#x2009;months, IgG1 was lower in the prebiotic group (95% CI: -1.55 [-3.55, -0.12]) compared to placebo group.<br><br>CONCLUSION: This exploratory study shows that prebiotic consumption by lactating mothers selectively alters specific immunomodulatory proteins in HM. This finding is crucial for understanding how prebiotic dietary recommendations for pregnant and lactating women can modify the immune properties of HM and potentially influence infant health outcomes through immune support from breastfeeding.}, }
@article {pmid39218882, year = {2024}, author = {Zhuang, Z and Lin, J and Wan, Z and Weng, J and Yuan, Z and Xie, Y and Liu, Z and Xie, P and Mao, S and Wang, Z and Wang, X and Huang, M and Luo, Y and Yu, H}, title = {Radiogenomic profiling of global DNA methylation associated with molecular phenotypes and immune features in glioma.}, journal = {BMC medicine}, volume = {22}, number = {1}, pages = {352}, pmid = {39218882}, issn = {1741-7015}, mesh = {Humans ; *Glioma/genetics/immunology ; *DNA Methylation/genetics ; Female ; *Magnetic Resonance Imaging ; Male ; *Brain Neoplasms/genetics/diagnostic imaging/immunology/pathology ; Middle Aged ; Adult ; Machine Learning ; Phenotype ; Aged ; Biomarkers, Tumor/genetics ; }, abstract = {BACKGROUND: The radiogenomic analysis has provided valuable imaging biomarkers with biological insights for gliomas. The radiogenomic markers for molecular profile such as DNA methylation remain to be uncovered to assist the molecular diagnosis and tumor treatment.<br><br>METHODS: We apply the machine learning approaches to identify the magnetic resonance imaging (MRI) features that are associated with molecular profiles in 146 patients with gliomas, and the fitting models for each molecular feature (MoRad) are developed and validated. To provide radiological annotations for the molecular profiles, we devise two novel approaches called radiomic oncology (RO) and radiomic set enrichment analysis (RSEA).<br><br>RESULTS: The generated MoRad models perform well for profiling each molecular feature with radiomic features, including mutational, methylation, transcriptional, and protein profiles. Among them, the MoRad models have a remarkable performance in quantitatively mapping global DNA methylation. With RO and RSEA approaches, we find that global DNA methylation could be reflected by the heterogeneity in volumetric and textural features of enhanced regions in T2-weighted MRI. Finally, we demonstrate the associations of global DNA methylation with clinicopathological, molecular, and immunological features, including histological grade, mutations of IDH and ATRX, MGMT methylation, multiple methylation-high subtypes, tumor-infiltrating lymphocytes, and long-term survival outcomes.<br><br>CONCLUSIONS: Global DNA methylation is highly associated with radiological profiles in glioma. Radiogenomic global methylation is an imaging-based quantitative molecular biomarker that is associated with specific consensus molecular subtypes and immune features.}, }
@article {pmid39217206, year = {2024}, author = {Duller, S and Vrbancic, S and Szydłowski, &#x141; and Mahnert, A and Blohs, M and Predl, M and Kumpitsch, C and Zrim, V and Högenauer, C and Kosciolek, T and Schmitz, RA and Eberhard, A and Dragovan, M and Schmidberger, L and Zurabischvili, T and Weinberger, V and Moser, AM and Kolb, D and Pernitsch, D and Mohammadzadeh, R and Kühnast, T and Rattei, T and Moissl-Eichinger, C}, title = {Targeted isolation of Methanobrevibacter strains from fecal samples expands the cultivated human archaeome.}, journal = {Nature communications}, volume = {15}, number = {1}, pages = {7593}, pmid = {39217206}, issn = {2041-1723}, support = {P 30796//Austrian Science Fund (Fonds zur F&#xf6;rderung der Wissenschaftlichen Forschung)/ ; SFB F-83//Austrian Science Fund (Fonds zur F&#xf6;rderung der Wissenschaftlichen Forschung)/ ; COE 7//Austrian Science Fund (Fonds zur F&#xf6;rderung der Wissenschaftlichen Forschung)/ ; }, mesh = {*Methanobrevibacter/genetics/isolation &amp; purification/metabolism ; Humans ; *Feces/microbiology ; *Gastrointestinal Microbiome/genetics ; *Genome, Archaeal ; Methane/metabolism ; Phylogeny ; Adult ; Male ; Female ; Gastrointestinal Tract/microbiology ; }, abstract = {Archaea are vital components of the human microbiome, yet their study within the gastrointestinal tract (GIT) is limited by the scarcity of cultured representatives. Our study presents a method for the targeted enrichment and isolation of methanogenic archaea from human fecal samples. The procedure combines methane breath testing, in silico metabolic modeling, media optimization, FACS, dilution series, and genomic sequencing through Nanopore technology. Additional analyzes include the co-cultured bacteriome, comparative genomics of archaeal genomes, functional comparisons, and structure-based protein function prediction of unknown differential traits. Successful establishment of stable archaeal cultures from 14 out of 16 fecal samples yielded nine previously uncultivated strains, eight of which are absent from a recent archaeome genome catalog. Comparative genomic and functional assessments of Methanobrevibacter smithii and Candidatus Methanobrevibacter intestini strains from individual donors revealed features potentially associated with gastrointestinal diseases. Our work broadens available archaeal representatives for GIT studies, and offers insights into Candidatus Methanobrevibacter intestini genomes' adaptability in critical microbiome contexts.}, }
@article {pmid39214080, year = {2024}, author = {Carlino, N and Blanco-Míguez, A and Punčochář, M and Mengoni, C and Pinto, F and Tatti, A and Manghi, P and Armanini, F and Avagliano, M and Barcenilla, C and Breselge, S and Cabrera-Rubio, R and Calvete-Torre, I and Coakley, M and Cobo-Díaz, JF and De Filippis, F and Dey, H and Leech, J and Klaassens, ES and Knobloch, S and O'Neil, D and Quijada, NM and Sabater, C and Skírnisdóttir, S and Valentino, V and Walsh, L and ,  and Alvarez-Ordóñez, A and Asnicar, F and Fackelmann, G and Heidrich, V and Margolles, A and Marteinsson, VT and Rota Stabelli, O and Wagner, M and Ercolini, D and Cotter, PD and Segata, N and Pasolli, E}, title = {Unexplored microbial diversity from 2,500 food metagenomes and links with the human microbiome.}, journal = {Cell}, volume = {187}, number = {20}, pages = {5775-5795.e15}, doi = {10.1016/j.cell.2024.07.039}, pmid = {39214080}, issn = {1097-4172}, mesh = {Humans ; *Metagenome/genetics ; *Gastrointestinal Microbiome/genetics ; Microbiota/genetics ; Food Microbiology ; Metagenomics/methods ; Bacteria/genetics/classification ; }, abstract = {Complex microbiomes are part of the food we eat and influence our own microbiome, but their diversity remains largely unexplored. Here, we generated the open access curatedFoodMetagenomicData (cFMD) resource by integrating 1,950 newly sequenced and 583 public food metagenomes. We produced 10,899 metagenome-assembled genomes spanning 1,036 prokaryotic and 108 eukaryotic species-level genome bins (SGBs), including 320 previously undescribed taxa. Food SGBs displayed significant microbial diversity within and between food categories. Extension to >20,000 human metagenomes revealed that food SGBs accounted on average for 3% of the adult gut microbiome. Strain-level analysis highlighted potential instances of food-to-gut transmission and intestinal colonization (e.g., Lacticaseibacillus paracasei) as well as SGBs with divergent genomic structures in food and humans (e.g., Streptococcus gallolyticus and Limosilactobabillus mucosae). The cFMD expands our knowledge on food microbiomes, their role in shaping the human microbiome, and supports future uses of metagenomics for food quality, safety, and authentication.}, }
@article {pmid39211550, year = {2024}, author = {Chung, RS and Wong, S and Lin, D and Kokot, NC and Sinha, UK and Han, AY}, title = {Mechanisms of crosstalk between the oropharyngeal microbiome and human papillomavirus in oropharyngeal carcinogenesis: a mini review.}, journal = {Frontiers in oncology}, volume = {14}, number = {}, pages = {1425545}, pmid = {39211550}, issn = {2234-943X}, abstract = {Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer globally. Notably, human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma (OPSCC) is on the rise, accounting for 70% of all OPSCC cases. Persistent high-risk HPV infection is linked to various cancers, but HPV infection alone is not sufficient to cause cancer. Advances in next-generation sequencing have improved our understanding of changes in the human microbiome of cancerous environments. Yet, there remains a dearth of knowledge on the impact of HPV-microbiome crosstalk in HPV-positive OPSCC. In this review, we examine what is known about the oropharyngeal microbiome and the compositional shifts in this microbiome in HPV-positive OPSCC. We also review potential mechanisms of crosstalk between HPV and specific microorganisms. Additional research is needed to understand these interactions and their roles on cancer development and progression.}, }
@article {pmid39207108, year = {2024}, author = {Crouch, AL and Monsey, L and Rambeau, M and Ramos, C and Yracheta, JM and Anderson, MZ}, title = {Metagenomic discovery of microbial eukaryotes in stool microbiomes.}, journal = {mBio}, volume = {15}, number = {10}, pages = {e0206324}, pmid = {39207108}, issn = {2150-7511}, support = {//Ohio State University (OSU)/ ; 2046863//National Science Foundation (NSF)/ ; //Chan Zuckerberg Initiative (CZI)/ ; }, mesh = {Humans ; *Metagenomics/methods ; *Feces/microbiology ; *Eukaryota/genetics/classification/isolation &amp; purification ; Gastrointestinal Microbiome/genetics ; Metagenome ; Fungi/genetics/classification/isolation &amp; purification ; Sequence Analysis, DNA/methods ; Microbiota/genetics ; }, abstract = {Host-associated microbiota form complex microbial communities that are increasingly associated with host behavior and disease. While these microbes include bacterial, archaeal, viral, and eukaryotic constituents, most studies have focused on bacteria due to their dominance in the human host and available tools for investigation. Accumulating evidence suggests microbial eukaryotes in the microbiome play pivotal roles in host health, but our understandings of these interactions are limited to a few readily identifiable taxa because of technical limitations in unbiased eukaryote exploration. Here, we combined cell sorting, optimized eukaryotic cell lysis, and shotgun sequencing to accelerate metagenomic discovery and analysis of host-associated microbial eukaryotes. Using synthetic communities with a 1% microbial eukaryote representation, the eukaryote-optimized cell lysis and DNA recovery method alone yielded a 38-fold increase in eukaryotic DNA. Automated sorting of eukaryotic cells from stool samples of healthy adults increased the number of microbial eukaryote reads in metagenomic pools by up to 28-fold compared to commercial kits. Read frequencies for identified fungi increased by 10,000× on average compared to the Human Microbiome Project and allowed for the identification of novel taxa, de novo assembly of contigs from previously unknown microbial eukaryotes, and gene prediction from recovered genomic segments. These advances pave the way for the unbiased inclusion of microbial eukaryotes in deciphering determinants of health and disease in the host-associated microbiome.IMPORTANCEMicrobial eukaryotes are common constituents of the human gut where they can contribute to local ecology and host health, but they are often overlooked in microbiome studies. The lack of attention is due to current technical limitations that are heavily biased or poorly recovered DNA from microbial eukaryotes. We developed a method to increase the representation of these eukaryotes in metagenomic sequencing of microbiome samples that allows to improve their detection compared to prior methods and allows for the identification of new species. Application of the technique to gut microbiome samples improved detection of fungi, protists, and helminths. New eukaryotic taxa and their encoded genes could be identified by sequencing a small number of samples. This approach can improve the inclusion of eukaryotes into microbiome research.}, }
@article {pmid39206540, year = {2024}, author = {Walker, M and Federico, E and Espinoza, JL and Dupont, CL}, title = {Unveiling Molecular Diversity in Cerebral Thrombi via Spatial Transcriptomics.}, journal = {Stroke}, volume = {55}, number = {10}, pages = {e266-e268}, pmid = {39206540}, issn = {1524-4628}, support = {R01 AI170111/AI/NIAID NIH HHS/United States ; }, mesh = {Humans ; Gene Expression Profiling ; *Intracranial Thrombosis/genetics ; *Transcriptome ; }, }
@article {pmid39206530, year = {2024}, author = {Gupta, CL and Jaganathasamy, N and Madkaikar, M}, title = {Microbiome in sickle cell disease: Pathophysiology and therapeutic insights.}, journal = {British journal of haematology}, volume = {205}, number = {4}, pages = {1279-1287}, doi = {10.1111/bjh.19736}, pmid = {39206530}, issn = {1365-2141}, mesh = {*Anemia, Sickle Cell/therapy/microbiology/complications/physiopathology ; Humans ; *Gastrointestinal Microbiome ; Probiotics/therapeutic use ; Fecal Microbiota Transplantation ; }, abstract = {Sickle cell disease (SCD) is a complex genetic blood disorder characterized by abnormal haemoglobin, resulting in sickle-shaped red blood cells. While extensive research has concentrated on the genetic and physiological aspects of SCD, recent studies suggest a potential role of the human microbiome in SCD pathophysiology, adding new dimensions to its understanding. This review synthesizes current knowledge on the microbiome's involvement in SCD, focusing on alterations in the gut microbiome composition and diversity compared to healthy individuals, and their implications for disease pathogenesis. We explore how microbiome changes may contribute to vaso-occlusive crises and other complications, along with the possible associations of specific microbial taxa or markers with disease crises and clinical outcomes. Additionally, we discuss the potential of microbiome-targeted interventions, including probiotics, dietary modifications, and faecal microbiota transplantation, in managing SCD complications and improving patient outcomes. Understanding the intricate relationship between the microbiome and SCD could lead to innovative therapeutic strategies and personalized interventions for better managing the disease. This review underscores the importance of further microbiome research and its integration into holistic SCD care.}, }
@article {pmid39203520, year = {2024}, author = {Maslennikov, R and Benuni, N and Levshina, A and Adzhieva, F and Demina, T and Kucher, A and Pervushova, E and Yuryeva, E and Poluektova, E and Zolnikova, O and Kozlov, E and Sigidaev, A and Ivashkin, V}, title = {Effect of Saccharomyces boulardii on Liver Diseases: A Systematic Review.}, journal = {Microorganisms}, volume = {12}, number = {8}, pages = {}, pmid = {39203520}, issn = {2076-2607}, abstract = {We aimed to systematize the results of published studies on the use of Saccharomyces boulardii (SB) for the treatment of various liver disorders (CRD42022378050). Searches were conducted using PubMed and Scopus on 1 August 2022. The PubMed search was updated on 15 June 2024. The review included sixteen studies: ten experimental animal studies (EASs) and six randomized controlled trials (RCTs). The CNCM I-745 strain was used in 68.8% of the included studies. SB reduced the severity of many manifestations of cirrhosis, and lowered the Child-Pugh scores in RCT. SB reduced the serum concentrations of TNF-α, IL-1β, IL-6, and IL-4 in animals with metabolic dysfunction-associated steatotic liver disease (MASLD); lowered the serum TNF-α and IL-6 levels in experimental cirrhosis in rats; and reduced the CRP levels in decompensated cirrhosis. The EAS of MASLD revealed that SB reduced liver steatosis and inflammation and lowered the liver expression of genes of TNF-α, IL-1β, interferon-γ, and IL-10. In studies on experimental cirrhosis and MASLD, SB reduced the liver expression of genes of TGF-β, α-SMA, and collagen as well as liver fibrosis. SB reduced the abundance of Escherichia (Proteobacteria), increased the abundance of Bacteroidetes in the gut microbiota, prevented an increase in intestinal barrier permeability, and reduced bacterial translocation and endotoxemia.}, }
@article {pmid39203484, year = {2024}, author = {Węgrzyn, K and Jasińska, A and Janeczek, K and Feleszko, W}, title = {The Role of Postbiotics in Asthma Treatment.}, journal = {Microorganisms}, volume = {12}, number = {8}, pages = {}, pmid = {39203484}, issn = {2076-2607}, abstract = {In recent years, there has been abundant research concerning human microbiome and its impact on the host's health. Studies have shown that not only the commensal bacteria itself, but also postbiotics, understood as inanimate microorganisms, possibly with the presence of their components, may themselves have an effect on various elements of human physiology. In this review, we take a closer look at the specific ways in which postbiotics can alter immune response in allergic asthma, which is one of the most prevalent allergic diseases in today's world and a serious subject of concern. Through altering patients' immune response, not only to allergens but also to pathogens, postbiotics could have a significant role in lowering the number of asthma exacerbations. We suggest that more profound research should be undertaken in order to launch postbiotics into clinical standards of asthma treatment, given the greatly promising findings in terms of their immunomodulating potential.}, }
@article {pmid39201629, year = {2024}, author = {Kim, JH and Seo, H and Kim, S and Rahim, MA and Jo, S and Barman, I and Tajdozian, H and Sarafraz, F and Song, HY and Song, YS}, title = {Different Prostatic Tissue Microbiomes between High- and Low-Grade Prostate Cancer Pathogenesis.}, journal = {International journal of molecular sciences}, volume = {25}, number = {16}, pages = {}, pmid = {39201629}, issn = {1422-0067}, support = {RS-2024-00333544//National Research Foundation of Korea/ ; RS-2023-00219563//National Research Foundation of Korea/ ; Soonchunhyang University Research Fund//Soonchunhyang University/ ; }, mesh = {Male ; Humans ; *Prostatic Neoplasms/microbiology/pathology ; *Microbiota ; *Neoplasm Grading ; Bacteria/classification/genetics ; Prostate/microbiology/pathology ; Middle Aged ; Aged ; High-Throughput Nucleotide Sequencing ; Cell Proliferation ; Cell Line, Tumor ; }, abstract = {Numerous human pathologies, such as neoplasia, are related to particular bacteria and changes in microbiome constituents. To investigate the association between an imbalance of bacteria and prostate carcinoma, the microbiome and gene functionality from tissues of patients with high-grade prostate tumor (HGT) and low-grade prostate tumor (LGT) were compared utilizing next-generation sequencing (NGS) technology. The results showed abnormalities in the bacterial profiles between the HGT and LGT specimens, indicating alterations in the make-up of bacterial populations and gene functionalities. The HGT specimens showed higher frequencies of Cutibacterium, Pelomonas, and Corynebacterium genera than the LGT specimens. Cell proliferation and cytokine assays also showed a significant proliferation of prostate cancer cells and elevated cytokine levels in the cells treated with Cutibacterium, respectively, supporting earlier findings. In summary, the HGT and LGT specimens showed differences in bacterial populations, suggesting that different bacterial populations might characterize high-grade and low-grade prostate malignancies.}, }
@article {pmid39191760, year = {2024}, author = {Hartikainen, AK and Jalanka, J and Lahtinen, P and Ponsero, AJ and Mertsalmi, T and Finnegan, L and Crispie, F and Cotter, PD and Arkkila, P and Satokari, R}, title = {Fecal microbiota transplantation influences microbiota without connection to symptom relief in irritable bowel syndrome patients.}, journal = {NPJ biofilms and microbiomes}, volume = {10}, number = {1}, pages = {73}, pmid = {39191760}, issn = {2055-5008}, support = {316338//Academy of Finland (Suomen Akatemia)/ ; 323156//Academy of Finland (Suomen Akatemia)/ ; }, mesh = {*Irritable Bowel Syndrome/therapy/microbiology ; Humans ; *Fecal Microbiota Transplantation/methods ; *RNA, Ribosomal, 16S/genetics ; Female ; Male ; Adult ; Treatment Outcome ; *Gastrointestinal Microbiome ; Middle Aged ; Feces/microbiology ; Metagenomics/methods ; Bacteria/classification/genetics/isolation &amp; purification ; }, abstract = {Imbalanced microbiota may contribute to the pathophysiology of irritable bowel syndrome (IBS), thus fecal microbiota transplantation (FMT) has been suggested as a potential treatment. Previous studies on the relationship between clinical improvement and microbiota after FMT have been inconclusive. In this study, we used 16S rRNA gene amplicon and shotgun metagenomics data from a randomized, placebo controlled FMT trial on 49 IBS patients to analyze changes after FMT in microbiota composition and its functional potential, and to identify connections between microbiota and patients' clinical outcome. As a result, we found that the successful modulation of microbiota composition and functional profiles by FMT from a healthy donor was not associated with the resolution of symptoms in IBS patients. Notably, a donor derived strain of Prevotella copri dominated the microbiota in those patients in the FMT group who had a low relative abundance of P. copri pre-FMT. The results highlight the multifactorial nature of IBS and the role of recipient's microbiota in the colonization of donor's strains.}, }
@article {pmid39188957, year = {2024}, author = {Xiang, B and Hu, J and Zhang, M and Zhi, M}, title = {The involvement of oral bacteria in inflammatory bowel disease.}, journal = {Gastroenterology report}, volume = {12}, number = {}, pages = {goae076}, pmid = {39188957}, issn = {2052-0034}, abstract = {Microorganisms play an important role in the pathogenesis of inflammatory bowel disease (IBD). The oral cavity, the second-largest microbial niche, is connected to the gastro-intestinal tract. Ectopic gut colonization by oral microbes is a signature of IBD. Current studies suggest that patients with IBD often report more oral manifestations and these oral issues are closely linked with disease activity. Murine studies have indicated that several oral microbes exacerbate intestinal inflammation. Moreover, intestinal inflammation can promote oral microbial dysbiosis and the migration of oral microbes to the gastro-intestinal tract. The reciprocal consequences of oral microbial dysbiosis and IBD, specifically through metabolic alterations, have not yet been elucidated. In this review, we summarize the relationship between oral bacteria and IBD from multiple perspectives, including clinical manifestations, microbial dysbiosis, and metabolic alterations, and find that oral pathogens increase anti-inflammatory metabolites and decrease inflammation-related metabolites.}, }
@article {pmid39172744, year = {2024}, author = {Cabrera, LE and Jokiranta, ST and Mäki, S and Miettinen, S and Kant, R and Kareinen, L and Sironen, T and Pietilä, JP and Kantele, A and Kekäläinen, E and Lindgren, H and Mattila, P and Kipar, A and Vapalahti, O and Strandin, T}, title = {The assembly of neutrophil inflammasomes during COVID-19 is mediated by type I interferons.}, journal = {PLoS pathogens}, volume = {20}, number = {8}, pages = {e1012368}, pmid = {39172744}, issn = {1553-7374}, mesh = {*COVID-19/immunology ; Humans ; *Neutrophils/immunology/metabolism ; *Interferon Type I/metabolism/immunology ; *Inflammasomes/immunology/metabolism ; Animals ; *SARS-CoV-2/immunology ; Mice ; Male ; Female ; Middle Aged ; Immunity, Innate ; Adult ; Mice, Inbred C57BL ; }, abstract = {The severity of COVID-19 is linked to excessive inflammation. Neutrophils represent a critical arm of the innate immune response and are major mediators of inflammation, but their role in COVID-19 pathophysiology remains poorly understood. We conducted transcriptomic profiling of neutrophils obtained from patients with mild and severe COVID-19, as well as from SARS-CoV-2 infected mice, in comparison to non-infected healthy controls. In addition, we investigated the inflammasome formation potential in neutrophils from patients and mice upon SARS-CoV-2 infection. Transcriptomic analysis of polymorphonuclear cells (PMNs), consisting mainly of mature neutrophils, revealed a striking type I interferon (IFN-I) gene signature in severe COVID-19 patients, contrasting with mild COVID-19 and healthy controls. Notably, low-density granulocytes (LDGs) from severe COVID-19 patients exhibited an immature neutrophil phenotype and lacked this IFN-I signature. Moreover, PMNs from severe COVID-19 patients showed heightened nigericin-induced caspase1 activation, but reduced responsiveness to exogenous inflammasome priming. Furthermore, IFN-I emerged as a priming stimulus for neutrophil inflammasomes. These findings suggest a potential role for neutrophil inflammasomes in driving inflammation during severe COVID-19. Altogether, these findings open promising avenues for targeted therapeutic interventions to mitigate the pathological processes associated with the disease.}, }
@article {pmid39167930, year = {2024}, author = {Mohamed, KA and Kruf, S and Büll, C}, title = {Putting a cap on the glycome: Dissecting human sialyltransferase functions.}, journal = {Carbohydrate research}, volume = {544}, number = {}, pages = {109242}, doi = {10.1016/j.carres.2024.109242}, pmid = {39167930}, issn = {1873-426X}, mesh = {Humans ; *Sialyltransferases/metabolism ; Polysaccharides/metabolism/chemistry ; }, abstract = {Human glycans are capped with sialic acids and these nine-carbon sugars mediate many of the biological functions and interactions of glycans. Structurally diverse sialic acid caps mark human cells as self and they form the ligands for the Siglec immune receptors and other glycan-binding proteins. Sialic acids enable host interactions with the human microbiome and many human pathogens utilize sialic acids to infect host cells. Alterations in sialic acid-carrying glycans, sialoglycans, can be found in every major human disease including inflammatory conditions and cancer. Twenty sialyltransferase family members in the Golgi apparatus of human cells transfer sialic acids to distinct glycans and glycoconjugates. Sialyltransferases catalyze specific reactions to form unique sialoglycans or they have shared functions where multiple family members generate the same sialoglycan product. Moreover, some sialyltransferases compete for the same glycan substrate, but create different sialic acid caps. The redundant and competing functions make it difficult to understand the individual roles of the human sialyltransferases in biology and to reveal the specific contributions to pathobiological processes. Recent insights hint towards the existence of biosynthetic rules formed by the individual functions of sialyltransferases, their interactions, and cues from the local Golgi environment that coordinate sialoglycan biosynthesis. In this review, we discuss the current structural and functional understanding of the human sialyltransferase family and we review recent technological advances that enable the dissection of individual sialyltransferase activities.}, }
@article {pmid39166876, year = {2024}, author = {de Palma, TH and Powers, C and McPartland, MJ and Mark Welch, J and Ramsey, M}, title = {Essential genes for Haemophilus parainfluenzae survival and biofilm growth.}, journal = {mSystems}, volume = {9}, number = {9}, pages = {e0067424}, pmid = {39166876}, issn = {2379-5077}, support = {R01 DE027958/DE/NIDCR NIH HHS/United States ; 1017848//U.S. Department of Agriculture (USDA)/ ; R01DE027958//HHS | NIH | National Institute of Dental and Craniofacial Research (NIDCR)/ ; }, mesh = {*Biofilms/growth &amp; development ; *Haemophilus parainfluenzae/genetics ; *Genes, Essential/genetics ; Humans ; Genome, Bacterial/genetics ; DNA Transposable Elements/genetics ; Microbial Viability/genetics ; }, abstract = {Haemophilus parainfluenzae (Hp) is a Gram-negative, highly prevalent, and abundant commensal in the human oral cavity, and an infrequent extraoral opportunistic pathogen. Hp occupies multiple niches in the oral cavity, including the supragingival plaque biofilm. Little is known about how Hp interacts with its neighbors in healthy biofilms nor its mechanisms of pathogenesis as an opportunistic pathogen. To address this, we identified the essential genome and conditionally essential genes in in vitro biofilms aerobically and anaerobically. Using transposon insertion sequencing (TnSeq) with a highly saturated mariner transposon library in two strains, the ATCC33392 type-strain (Hp 392) and oral isolate EL1 (Hp EL1), we show that the essential genomes of Hp 392 and Hp EL1 are composed of 395 (20%) and 384 (19%) genes, respectively. The core essential genome, consisting of 341 (17%) essential genes conserved between both strains, was composed of genes associated with genetic information processing, carbohydrate, protein, and energy metabolism. We also identified conditionally essential genes for aerobic and anaerobic biofilm growth, which were associated with carbohydrate and energy metabolism in both strains. RNAseq analysis determined that most genes upregulated during anaerobic growth are not essential for Hp 392 anaerobic survival. The completion of this library and analysis under these conditions gives us a foundational insight into the basic biology of H. parainfluenzae in differing oxygen conditions, similar to its in vivo habitat. This library presents a valuable tool for investigation into conditionally essential genes for an organism that lives in close contact with many microbial species in the human oral habitat.IMPORTANCEHaemophilus parainfluenzae is a highly abundant human commensal microbe, present in most healthy individuals where it colonizes the mouth. H. parainfluenzae correlates with good oral health and may play a role in preservation of healthy host status. Also, H. parainfluenzae can cause opportunistic infections outside of the oral cavity. To date, little is known about how H. parainfluenzae colonizes the human host, despite being such a frequent and abundant part of our human microbiome. Here, we demonstrate the creation and use of a powerful tool, a TnSeq library, used to identify genes necessary for both the outright growth of this organism and also genes conditionally essential for growth in varying oxygen status which it can encounter in the human host. This tool and these data serve as a foundation for further study of this relatively unknown organism that may play a role in preserving human health.}, }
@article {pmid39163860, year = {2024}, author = {Torres, MDT and Brooks, EF and Cesaro, A and Sberro, H and Gill, MO and Nicolaou, C and Bhatt, AS and de la Fuente-Nunez, C}, title = {Mining human microbiomes reveals an untapped source of peptide antibiotics.}, journal = {Cell}, volume = {187}, number = {19}, pages = {5453-5467.e15}, doi = {10.1016/j.cell.2024.07.027}, pmid = {39163860}, issn = {1097-4172}, mesh = {Humans ; Animals ; Mice ; *Anti-Bacterial Agents/pharmacology ; *Microbiota/drug effects ; *Antimicrobial Peptides/pharmacology/chemistry ; Metagenome ; Female ; Open Reading Frames ; Bacteria/drug effects/genetics/classification ; Prevotella/drug effects ; }, abstract = {Drug-resistant bacteria are outpacing traditional antibiotic discovery efforts. Here, we computationally screened 444,054 previously reported putative small protein families from 1,773 human metagenomes for antimicrobial properties, identifying 323 candidates encoded in small open reading frames (smORFs). To test our computational predictions, 78 peptides were synthesized and screened for antimicrobial activity in vitro, with 70.5% displaying antimicrobial activity. As these compounds were different compared with previously reported antimicrobial peptides, we termed them smORF-encoded peptides (SEPs). SEPs killed bacteria by targeting their membrane, synergizing with each other, and modulating gut commensals, indicating a potential role in reconfiguring microbiome communities in addition to counteracting pathogens. The lead candidates were anti-infective in both murine skin abscess and deep thigh infection models. Notably, prevotellin-2 from Prevotella copri presented activity comparable to the commonly used antibiotic polymyxin B. Our report supports the existence of hundreds of antimicrobials in the human microbiome amenable to clinical translation.}, }
@article {pmid39160377, year = {2024}, author = {Li, Q and Liu, D and Liang, M and Zhu, Y and Yousaf, M and Wu, Y}, title = {Mechanism of probiotics in the intervention of colorectal cancer: a review.}, journal = {World journal of microbiology &amp; biotechnology}, volume = {40}, number = {10}, pages = {306}, pmid = {39160377}, issn = {1573-0972}, mesh = {*Probiotics/therapeutic use ; Humans ; *Colorectal Neoplasms/microbiology/prevention &amp; control/therapy ; *Gastrointestinal Microbiome ; Apoptosis ; Animals ; Bacteria/metabolism ; }, abstract = {The human microbiome interacts with the host mainly in the intestinal lumen, where putrefactive bacteria are suggested to promote colorectal cancer (CRC). In contrast, probiotics and their isolated components and secreted substances, display anti-tumor properties due to their ability to modulate gut microbiota composition, promote apoptosis, enhance immunity, resist oxidation and alter metabolism. Probiotics help to form a solid intestinal barrier against damaging agents via altering the gut microbiota and preventing harmful microbes from colonization. Probiotic strains that specifically target essential proteins involved in the process of apoptosis can overcome CRC resistance to apoptosis. They can increase the production of anti-inflammatory cytokines, essential in preventing carcinogenesis, and eliminate cancer cells by activating T cell-mediated immune responses. There is a clear indication that probiotics optimize the antioxidant system, decrease radical generation, and detect and degrade potential carcinogens. In this review, the pathogenic mechanisms of pathogens in CRC and the recent insights into the mechanism of probiotics in CRC prevention and therapy are discussed to provide a reference for the actual application of probiotics in CRC.}, }
@article {pmid39152482, year = {2024}, author = {Luo, W and Zhao, M and Dwidar, M and Gao, Y and Xiang, L and Wu, X and Medema, MH and Xu, S and Li, X and Schäfer, H and Chen, M and Feng, R and Zhu, Y}, title = {Microbial assimilatory sulfate reduction-mediated H2S: an overlooked role in Crohn's disease development.}, journal = {Microbiome}, volume = {12}, number = {1}, pages = {152}, pmid = {39152482}, issn = {2049-2618}, support = {82370551//National Natural Science Foundation of China/ ; 82270579//National Natural Science Foundation of China/ ; 82100577//National Natural Science Foundation of China/ ; 2024GXNSFFA010009//Natural Science Foundation of Guangxi Zhuang Autonomous Region/ ; }, mesh = {*Crohn Disease/microbiology ; Humans ; *Gastrointestinal Microbiome ; *Hydrogen Sulfide/metabolism ; Animals ; Mice ; *Sulfates/metabolism ; Escherichia coli/genetics/metabolism ; Feces/microbiology ; Dysbiosis/microbiology ; Colon/microbiology ; Metagenomics ; Oxidation-Reduction ; Disease Models, Animal ; Female ; }, abstract = {BACKGROUND: H2S imbalances in the intestinal tract trigger Crohn's disease (CD), a chronic inflammatory gastrointestinal disorder characterized by microbiota dysbiosis and barrier dysfunction. However, a comprehensive understanding of H2S generation in the gut, and the contributions of both microbiota and host to systemic H2S levels in CD, remain to be elucidated. This investigation aimed to enhance comprehension regarding the sulfidogenic potential of both the human host and the gut microbiota.<br><br>RESULTS: Our analysis of a treatment-naive CD cohorts' fecal metagenomic and biopsy metatranscriptomic data revealed reduced expression of host endogenous H2S generation genes alongside increased abundance of microbial exogenous H2S production genes in correlation with CD. While prior studies focused on microbial H2S production via dissimilatory sulfite reductases, our metagenomic analysis suggests the assimilatory sulfate reduction (ASR) pathway is a more significant contributor in the human gut, given its high prevalence and abundance. Subsequently, we validated our hypothesis experimentally by generating ASR-deficient E. coli mutants &#x2206;cysJ and &#x2206;cysM through the deletion of sulfite reductase and L-cysteine synthase genes. This alteration significantly affected bacterial sulfidogenic capacity, colon epithelial cell viability, and colonic mucin sulfation, ultimately leading to colitis in murine model. Further study revealed that gut microbiota degrade sulfopolysaccharides and assimilate sulfate to produce H2S via the ASR pathway, highlighting the role of sulfopolysaccharides in colitis and cautioning against their use as food additives.<br><br>CONCLUSIONS: Our study significantly advances understanding of microbial sulfur metabolism in the human gut, elucidating the complex interplay between diet, gut microbiota, and host sulfur metabolism. We highlight the microbial ASR pathway as an overlooked endogenous H2S producer and a potential therapeutic target for managing CD. Video Abstract.}, }
@article {pmid39148051, year = {2024}, author = {Zhu, H and Hao, H and Yu, L}, title = {Identification of microbe-disease signed associations via multi-scale variational graph autoencoder based on signed message propagation.}, journal = {BMC biology}, volume = {22}, number = {1}, pages = {172}, pmid = {39148051}, issn = {1741-7007}, support = {62072353//National Natural Science Foundation of China/ ; 62272065//National Natural Science Foundation of China/ ; }, mesh = {Humans ; *Microbiota ; Computational Biology/methods ; Algorithms ; Disease ; }, abstract = {BACKGROUND: Plenty of clinical and biomedical research has unequivocally highlighted the tremendous significance of the human microbiome in relation to human health. Identifying microbes associated with diseases is crucial for early disease diagnosis and advancing precision medicine.<br><br>RESULTS: Considering that the information about changes in microbial quantities under fine-grained disease states helps to enhance a comprehensive understanding of the overall data distribution, this study introduces MSignVGAE, a framework for predicting microbe-disease sign associations using signed message propagation. MSignVGAE employs a graph variational autoencoder to model noisy signed association data and extends the multi-scale concept to enhance representation capabilities. A novel strategy for propagating signed message in signed networks addresses heterogeneity and consistency among nodes connected by signed edges. Additionally, we utilize the idea of denoising autoencoder to handle the noise in similarity feature information, which helps overcome biases in the fused similarity data. MSignVGAE represents microbe-disease associations as a heterogeneous graph using similarity information as node features. The multi-class classifier XGBoost is utilized to predict sign associations between diseases and microbes.<br><br>CONCLUSIONS: MSignVGAE achieves AUROC and AUPR values of 0.9742 and 0.9601, respectively. Case studies on three diseases demonstrate that MSignVGAE can effectively capture a comprehensive distribution of associations by leveraging signed information.}, }
@article {pmid39146817, year = {2025}, author = {Caukwell, J and Assenza, S and Hassan, KA and Neilan, BA and Clulow, AJ and Salvati Manni, L and Fong, WK}, title = {Lipidic drug delivery systems are responsive to the human microbiome.}, journal = {Journal of colloid and interface science}, volume = {677}, number = {Pt B}, pages = {293-302}, doi = {10.1016/j.jcis.2024.07.216}, pmid = {39146817}, issn = {1095-7103}, mesh = {Humans ; *Staphylococcus aureus/drug effects ; *Microbiota/drug effects ; *Drug Delivery Systems ; Glycerides/chemistry ; Drug Liberation ; Lipids/chemistry ; Nanostructures/chemistry ; Drug Carriers/chemistry ; Particle Size ; }, abstract = {In vitro and in vivo tests for therapeutic agents are typically conducted in sterile environments, but many target areas for drug delivery are home to thousands of microbial species. Here, we examine the behaviour of lipidic nanomaterials after exposure to representative strains of four bacterial species found in the gastrointestinal tract and skin. Small angle X-ray scattering measurements show that the nanostructure of monoolein cubic and inverse hexagonal phases are transformed, respectively, into inverse hexagonal and inverse micellar cubic phases upon exposure to a strain of live Staphylococcus aureus often present on skin and mucosa. Further investigation demonstrates that enzymatic hydrolysis and cell membrane lipid transfer are both likely responsible for this effect. The structural responses to S. aureus are rapid and significantly reduce the rate of drug release from monoolein-based nanomaterials. These findings are the first to demonstrate how a key species in the live human microbiome can trigger changes in the structure and drug release properties of lipidic nanomaterials. The effect appears to be strain specific, varies from patient to patient and body region to body region, and is anticipated to affect the bioapplication of monoglyceride-based formulations.}, }
@article {pmid39146797, year = {2024}, author = {Castells-Nobau, A and Mayneris-Perxachs, J and Fernández-Real, JM}, title = {Unlocking the mind-gut connection: Impact of human microbiome on cognition.}, journal = {Cell host &amp; microbe}, volume = {32}, number = {8}, pages = {1248-1263}, doi = {10.1016/j.chom.2024.07.019}, pmid = {39146797}, issn = {1934-6069}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Cognition/physiology ; *Brain-Gut Axis/physiology ; Brain/physiology/microbiology ; Bacteria ; Metabolic Diseases/microbiology ; }, abstract = {This perspective explores the current understanding of the gut microbiota's impact on cognitive function in apparently healthy humans and in individuals with metabolic disease. We discuss how alterations in gut microbiota can influence cognitive processes, focusing not only on bacterial composition but also on often overlooked components of the gut microbiota, such as bacteriophages and eukaryotes, as well as microbial functionality. We examine the mechanisms through which gut microbes might communicate with the central nervous system, highlighting the complexity of these interactions. We provide a comprehensive overview of the emerging field of microbiota-gut-brain interactions and its significance for cognitive health. Additionally, we summarize novel therapeutic strategies designed to promote cognitive resilience and reduce the risk of cognitive disorders, focusing on interventions that target the gut microbiota. An in-depth understanding of the microbiome-brain axis is imperative for developing innovative treatments aimed at improving cognitive health.}, }
@article {pmid39143108, year = {2024}, author = {Grahnemo, L and Kambur, O and Lahti, L and Jousilahti, P and Niiranen, T and Knight, R and Salomaa, V and Havulinna, AS and Ohlsson, C}, title = {Associations between gut microbiota and incident fractures in the FINRISK cohort.}, journal = {NPJ biofilms and microbiomes}, volume = {10}, number = {1}, pages = {69}, pmid = {39143108}, issn = {2055-5008}, support = {NNF 190C0055250 and 22OC0078421//Novo Nordisk Fonden (Novo Nordisk Foundation)/ ; 101096347/ERC_/European Research Council/International ; KAW 2015.0317//Knut och Alice Wallenbergs Stiftelse (Knut and Alice Wallenberg Foundation)/ ; LU2021-0096//IngaBritt och Arne Lundbergs Forskningsstiftelse (Ingabritt and Arne Lundberg Research Foundation)/ ; 2020-01392//Vetenskapsr&#xe5;det (Swedish Research Council)/ ; }, mesh = {*Gastrointestinal Microbiome ; Humans ; Male ; Female ; *Fractures, Bone/microbiology/epidemiology/etiology ; Middle Aged ; Finland/epidemiology ; Aged ; Bacteria/classification/genetics/isolation &amp; purification ; Metagenome ; Cohort Studies ; Incidence ; Metagenomics/methods ; Proteobacteria/genetics/isolation &amp; purification ; Risk Factors ; Adult ; }, abstract = {The gut microbiota (GM) can regulate bone mass, but its association with incident fractures is unknown. We used Cox regression models to determine whether the GM composition is associated with incident fractures in the large FINRISK 2002 cohort (n = 7043, 1092 incident fracture cases, median follow-up time 18 years) with information on GM composition and functionality from shotgun metagenome sequencing. Higher alpha diversity was associated with decreased fracture risk (hazard ratio [HR] 0.92 per standard deviation increase in Shannon index, 95% confidence interval 0.87-0.96). For beta diversity, the first principal component was associated with fracture risk (Aitchison distance, HR 0.90, 0.85-0.96). In predefined phyla analyses, we observed that the relative abundance of Proteobacteria was associated with increased fracture risk (HR 1.14, 1.07-1.20), while the relative abundance of Tenericutes was associated with decreased fracture risk (HR 0.90, 0.85-0.96). Explorative sub-analyses within the Proteobacteria phylum showed that higher relative abundance of Gammaproteobacteria was associated with increased fracture risk. Functionality analyses showed that pathways related to amino acid metabolism and lipopolysaccharide biosynthesis associated with fracture risk. The relative abundance of Proteobacteria correlated with pathways for amino acid metabolism, while the relative abundance of Tenericutes correlated with pathways for butyrate synthesis. In conclusion, the overall GM composition was associated with incident fractures. The relative abundance of Proteobacteria, especially Gammaproteobacteria, was associated with increased fracture risk, while the relative abundance of Tenericutes was associated with decreased fracture risk. Functionality analyses demonstrated that pathways known to regulate bone health may underlie these associations.}, }
@article {pmid39139405, year = {2024}, author = {Attaye, I and Witjes, JJ and Koopen, AM and van der Vossen, EWJ and Zwirs, D and Wortelboer, K and Collard, D and Kemper, EM and Winkelmeijer, M and Holst, JJ and Hazen, SL and Kuipers, F and Stroes, ESG and Groen, AK and de Vos, WM and Nieuwdorp, M and Herrema, H}, title = {Oral Anaerobutyricum soehngenii augments glycemic control in type 2 diabetes.}, journal = {iScience}, volume = {27}, number = {8}, pages = {110455}, pmid = {39139405}, issn = {2589-0042}, support = {P01 HL147823/HL/NHLBI NIH HHS/United States ; R01 HL103866/HL/NHLBI NIH HHS/United States ; }, abstract = {This randomized, double-blind, placebo-controlled trial investigated the impact of 14-day Anaerobutyricum soehngenii L2-7 supplementation on postprandial glucose levels in 25 White Dutch males with type 2 diabetes (T2D) on stable metformin therapy. The primary endpoint was the effect of A. soehngenii versus placebo on glucose excursions and variability as determined by continuous glucose monitoring. Secondary endpoints were changes in ambulatory 24-h blood pressure, incretins, circulating metabolites and excursions of plasma short-chain fatty acids (SCFAs) and bile acids upon a standardized meal. Results showed that A. soehngenii supplementation for 14 days significantly improved glycemic variability and mean arterial blood pressure, without notable changes in SCFAs, bile acids, incretin levels, or anthropometric parameters as compared to placebo-treated controls. Although well-tolerated and effective in improving glycemic control in the intervention group, further research in larger and more diverse populations is needed to generalize these findings.}, }
@article {pmid39137463, year = {2024}, author = {Fang, Q and Qiu, T and Ye, T and Feng, Z and Tian, X and Cao, Y and Bai, J and Liu, Y}, title = {Prenatal ozone exposure and variations of the gut microbiome: Evidence from a Chinese mother-infant cohort.}, journal = {Ecotoxicology and environmental safety}, volume = {283}, number = {}, pages = {116861}, doi = {10.1016/j.ecoenv.2024.116861}, pmid = {39137463}, issn = {1090-2414}, mesh = {Humans ; *Ozone/toxicity ; *Gastrointestinal Microbiome/drug effects ; Female ; Pregnancy ; China ; Cohort Studies ; Adult ; Infant, Newborn ; *Maternal Exposure/adverse effects ; *Prenatal Exposure Delayed Effects/microbiology ; Air Pollutants/toxicity ; Infant ; Male ; Child, Preschool ; RNA, Ribosomal, 16S/genetics ; East Asian People ; }, abstract = {BACKGROUND: The gut microbiome is central to human health, but the potential impact of ozone (O3) exposure on its establishment in early life has not been thoroughly examined. Therefore, this study aimed to investigate the relationship between prenatal O3 exposure and the variations of the human gut microbiome during the first two years of life.<br><br>DESIGN: A cohort study design was used. Pregnant women in the third trimester were recruited from an obstetric clinic, and long-term follow-ups were conducted after delivery. The gut microbiome was analyzed using the 16&#x202f;S rRNA V3-V4 gene regions. Functional pathway analyses of gut microbial communities in neonates were performed using Tax4fun. The average concentrations of ambient O3 and other air pollutants from pregnancy to delivery were calculated using the China High Air Pollutants (CHAP) dataset, based on the permanent residential addresses of participants. Multiple linear regression and mixed linear models were utilized to investigate the associations between prenatal O3 exposure and gut microbiome features.<br><br>RESULTS: Prenatal O3 exposure did not significantly affect the gut microbial alpha diversity of mothers and neonates. However, it was found to be positively associated with the gut microbial alpha diversity in 24-month-old infants. Prenatal O3 exposure explained 13.1&#x202f;% of the variation in neonatal gut microbial composition. After controlling for potential covariates, prenatal O3 exposure was associated with neonatal-specific gut microbial taxa and functional pathways. Furthermore, the mixed linear models showed that prenatal O3 exposure was negatively associated with variations of Streptococcus (p-value = 0.001, q-value = 0.005), Enterococcus (p-value = 0.001, q-value = 0.005), Escherichia-Shigella (p-value = 0.010, q-value = 0.025), and Bifidobacterium (p-value = 0.003, q-value = 0.010).<br><br>CONCLUSIONS: This study is the first to examine the effects of prenatal O3 exposure on gut microbial homeostasis and variations. It demonstrates that prenatal O3 exposure is associated with variations in certain aspects of the gut microbiome. These findings provide novel insights into the dynamics and establishment of the human microbiome during the first two years of life.}, }
@article {pmid39136453, year = {2024}, author = {Etlin, S and Rose, J and Bielski, L and Walter, C and Kleinman, AS and Mason, CE}, title = {The human microbiome in space: parallels between Earth-based dysbiosis, implications for long-duration spaceflight, and possible mitigation strategies.}, journal = {Clinical microbiology reviews}, volume = {37}, number = {3}, pages = {e0016322}, pmid = {39136453}, issn = {1098-6618}, mesh = {Humans ; *Space Flight ; *Dysbiosis/microbiology ; *Astronauts ; Microbiota/physiology ; Gastrointestinal Microbiome/physiology ; }, abstract = {SUMMARYThe human microbiota encompasses the diverse communities of microorganisms that reside in, on, and around various parts of the human body, such as the skin, nasal passages, and gastrointestinal tract. Although research is ongoing, it is well established that the microbiota exert a substantial influence on the body through the production and modification of metabolites and small molecules. Disruptions in the composition of the microbiota-dysbiosis-have also been linked to various negative health outcomes. As humans embark upon longer-duration space missions, it is important to understand how the conditions of space travel impact the microbiota and, consequently, astronaut health. This article will first characterize the main taxa of the human gut microbiota and their associated metabolites, before discussing potential dysbiosis and negative health consequences. It will also detail the microbial changes observed in astronauts during spaceflight, focusing on gut microbiota composition and pathogenic virulence and survival. Analysis will then turn to how astronaut health may be protected from adverse microbial changes via diet, exercise, and antibiotics before concluding with a discussion of the microbiota of spacecraft and microbial culturing methods in space. The implications of this review are critical, particularly with NASA's ongoing implementation of the Moon to Mars Architecture, which will include weeks or months of living in space and new habitats.}, }
@article {pmid39125810, year = {2024}, author = {Rezzani, R and Favero, G and Cominelli, G and Pinto, D and Rinaldi, F}, title = {Skin Aging and the Upcoming Role of Ferroptosis in Geroscience.}, journal = {International journal of molecular sciences}, volume = {25}, number = {15}, pages = {}, pmid = {39125810}, issn = {1422-0067}, mesh = {*Ferroptosis ; Humans ; *Skin Aging ; Iron/metabolism ; Animals ; Skin/metabolism/pathology ; Aging/metabolism ; Geriatrics ; }, abstract = {The skin is considered the most important organ system in mammals, and as the population ages, it is important to consider skin aging and anti-aging therapeutic strategies. Exposure of the skin to various insults induces significant changes throughout our lives, differentiating the skin of a young adult from that of an older adult. These changes are caused by a combination of intrinsic and extrinsic aging. We report the interactions between skin aging and its metabolism, showing that the network is due to several factors. For example, iron is an important nutrient for humans, but its level increases with aging, inducing deleterious effects on cellular functions. Recently, it was discovered that ferroptosis, or iron-dependent cell death, is linked to aging and skin diseases. The pursuit of new molecular targets for ferroptosis has recently attracted attention. Prevention of ferroptosis is an effective therapeutic strategy for the treatment of diseases, especially in old age. However, the pathological and biological mechanisms underlying ferroptosis are still not fully understood, especially in skin diseases such as melanoma and autoimmune diseases. Only a few basic studies on regulated cell death exist, and the challenge is to turn the studies into clinical applications.}, }
@article {pmid39122010, year = {2024}, author = {Hashimoto, Y and Ishigami, K and Hassaninasab, A and Kishi, K and Kumano, T and Kobayashi, M}, title = {Curcumin degradation in a soil microorganism: Screening and characterization of a β-diketone hydrolase.}, journal = {The Journal of biological chemistry}, volume = {300}, number = {9}, pages = {107647}, pmid = {39122010}, issn = {1083-351X}, mesh = {*Curcumin/metabolism/analogs &amp; derivatives/chemistry ; *Soil Microbiology ; *Rhodococcus/enzymology/genetics/metabolism ; Humans ; Bacterial Proteins/metabolism/genetics/chemistry ; Hydrolases/metabolism/chemistry/genetics ; Ketones/metabolism/chemistry ; Substrate Specificity ; }, abstract = {Curcumin is a plant-derived secondary metabolite exhibiting antitumor, neuroprotective, antidiabetic activities, and so on. We previously isolated Escherichia coli as an enterobacterium exhibiting curcumin-converting activity from human feces, and discovered an enzyme showing this activity (CurA) and named it NADPH-dependent curcumin/dihydrocurcumin reductase. From soil, here, we isolated a curcumin-degrading microorganism (No. 34) using the screening medium containing curcumin as the sole carbon source and identified as Rhodococcus sp. A curcumin-degrading enzyme designated as CurH was purified from this strain and characterized, and compared with CurA. CurH catalyzed hydrolytic cleavage of a carbon-carbon bond in the β-diketone moiety of curcumin and its analogs, yielding two products bearing a methyl ketone terminus and a carboxylic acid terminus, respectively. These findings demonstrated that a curcumin degradation reaction catalyzed by CurH in the soil environment was completely different from the one catalyzed by CurA in the human microbiome. Of all the curcumin analogs tested, suitable substrates for the enzyme were curcuminoids (i.e., curcumin and bisdemethoxycurcumin) and tetrahydrocurcuminoids. Thus, we named this enzyme curcuminoid hydrolase. The deduced amino acid sequence of curH exhibited similarity to those of members of acetyl-CoA C-acetyltransferase family. Considering results of oxygen isotope analyses and a series of site-directed mutagenesis experiments on our enzyme, we propose a possible catalytic mechanism of CurH, which is unique and distinct from those of enzymes degrading β-diketone moieties such as β-diketone hydrolases known so far.}, }
@article {pmid39119866, year = {2024}, author = {Schweitzer, M and Wlasak, M and Wassermann, B and Marcher, F and Poglitsch, C and Pirker, J and Berg, G}, title = {'Tiny Biome Tales': A gamified review about the influence of lifestyle choices on the human microbiome.}, journal = {Microbial biotechnology}, volume = {17}, number = {8}, pages = {e14544}, pmid = {39119866}, issn = {1751-7915}, support = {//Federal Ministry of Education, Science and Research, Austria/ ; }, mesh = {Humans ; *Microbiota ; *Video Games ; *Life Style ; Female ; Pregnancy ; Adult ; }, abstract = {In the last two decades, new discoveries from microbiome research have changed our understanding of human health. It became evident that daily habits and lifestyle choices shape the human microbiome and ultimately determine health or disease. Therefore, we developed 'Tiny Biome Tales' (https://microbiome.gamelabgraz.at/), a science pedagogy video game designed like a scientific review based exclusively on peer-reviewed articles, to teach about the influence of lifestyle choices on the human microbiome during pregnancy, early and adult life, and related health consequences. Despite the scientific character, it can be played by a broad audience. Here, we also present a scientific assessment and showed that playing the game significantly contributed to knowledge gain. The innovative style of the 'gamified review' represents an ideal platform to disseminate future findings from microbiome research by updating existing and adding new scenes to the game.}, }
@article {pmid39114281, year = {2024}, author = {Manske, S}, title = {The Microbiome: A Foundation for Integrative Medicine.}, journal = {Integrative medicine (Encinitas, Calif.)}, volume = {23}, number = {3}, pages = {28-31}, pmid = {39114281}, issn = {1546-993X}, abstract = {CONTEXT: No organ system better integrates interconnectivity across specialties and disciplines than the microbiome. Scientific focus is shifting from microbes as harbingers of disease toward microbes as symbiotic, balanced, commensal ecologies.<br><br>OBJECTIVE: The study intended to discuss and examine the human microbiome, including its development in early life; its impact on various physiological processes that occur throughout the body; and its relationship to dysbiosis; and to investigate microbial mechanisms with clinical applicability across medical specialties.<br><br>SETTING: The study took place at Biocidin Botanicals in Watsonville CA, USA.<br><br>RESULTS: Accumulating research upholds the human microbiome as both a predictive biomarker for disease risk and a viable treatment option for modulating the course of illness. Prebiotic and probiotic interventions continue to demonstrate clinical utility, particularly for gastrointestinal, dermatological, inflammatory, metabolic, and mental-health disorders.<br><br>CONCLUSIONS: Just as germ theory revolutionized infection control in the twentieth century, microbiome systems science stands to transform the conceptualization of health as the balanced coexistence of human and microbial cells in the twenty-first century.}, }
@article {pmid39113194, year = {2024}, author = {Tae, IH and Lee, J and Kang, Y and Lee, JM and Park, K and Yang, H and Kim, HW and Ko, JH and Park, DS and Kim, DS and Son, MY and Cho, HS}, title = {Induction of Cell Death by Bifidobacterium infantis DS1685 in Colorectal and Breast Cancers via SMAD4/TGF-Beta Activation.}, journal = {Journal of microbiology and biotechnology}, volume = {34}, number = {8}, pages = {1698-1704}, pmid = {39113194}, issn = {1738-8872}, mesh = {Humans ; *Smad4 Protein/metabolism/genetics ; *Breast Neoplasms/pathology/metabolism ; *Colorectal Neoplasms/microbiology/pathology ; Cell Line, Tumor ; *Transforming Growth Factor beta/metabolism ; *Bifidobacterium longum subspecies infantis/metabolism/genetics ; Female ; Cell Death/drug effects ; Cell Proliferation/drug effects ; Probiotics ; Antineoplastic Agents/pharmacology ; }, abstract = {Therapeutic advancements in treatments for cancer, a leading cause of mortality worldwide, have lagged behind the increasing incidence of this disease. There is a growing interest in multifaceted approaches for cancer treatment, such as chemotherapy, targeted therapy, and immunotherapy, but due to their low efficacy and severe side effects, there is a need for the development of new cancer therapies. Recently, the human microbiome, which is comprised of various microorganisms, has emerged as an important research field due to its potential impact on cancer treatment. Among these microorganisms, Bifidobacterium infantis has been shown to significantly improve the efficacy of various anticancer drugs. However, research on the role of B. infantis in cancer treatment remains insufficient. Thus, in this study, we explored the anticancer effect of treatment with B. infantis DS1685 supernatant (BI sup) in colorectal and breast cancer cell lines. Treatment with BI sup induced SMAD4 expression to suppress cell growth in colon and breast cancer cells. Furthermore, a decrease in tumor cohesion was observed through the disruption of the regulation of EMT-related genes by BI sup in 3D spheroid models. Based on these findings, we anticipate that BI sup could play an adjunctive role in cancer therapy, and future cotreatment of BI sup with various anticancer drugs may lead to synergistic effects in cancer treatment.}, }
@article {pmid39113097, year = {2024}, author = {Gray, SM and Moss, AD and Herzog, JW and Kashiwagi, S and Liu, B and Young, JB and Sun, S and Bhatt, AP and Fodor, AA and Balfour Sartor, R}, title = {Mouse adaptation of human inflammatory bowel diseases microbiota enhances colonization efficiency and alters microbiome aggressiveness depending on the recipient colonic inflammatory environment.}, journal = {Microbiome}, volume = {12}, number = {1}, pages = {147}, pmid = {39113097}, issn = {2049-2618}, support = {P01 DK094779/DK/NIDDK NIH HHS/United States ; P40 OD010995/OD/NIH HHS/United States ; P30 DK034987/DK/NIDDK NIH HHS/United States ; NSF Cooperative Agreement No. EEC-2133504//The Engineering Research Centers Program of the National Science Foundation/ ; T32DK007737//NIH/NIDDK/ ; T32 DK007737/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Humans ; Mice ; *Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; *Inflammatory Bowel Diseases/microbiology ; *Disease Models, Animal ; *Dysbiosis/microbiology ; *Interleukin-10/genetics ; Colitis/microbiology ; Feces/microbiology ; Colon/microbiology ; Mice, Knockout ; Mice, Inbred C57BL ; Female ; Bacteria/classification/genetics/isolation &amp; purification ; Inflammation ; Male ; }, abstract = {BACKGROUND: Understanding the cause vs consequence relationship of gut inflammation and microbial dysbiosis in inflammatory bowel diseases (IBD) requires a reproducible mouse model of human-microbiota-driven experimental colitis.<br><br>RESULTS: Our study demonstrated that human fecal microbiota transplant (FMT) transfer efficiency is an underappreciated source of experimental variability in human microbiota-associated (HMA) mice. Pooled human IBD patient fecal microbiota engrafted germ-free (GF) mice with low amplicon sequence variant (ASV)-level transfer efficiency, resulting in high recipient-to-recipient variation of microbiota composition and colitis severity in HMA Il-10[-/-] mice. In contrast, mouse-to-mouse transfer of mouse-adapted human IBD patient microbiota transferred with high efficiency and low compositional variability resulting in highly consistent and reproducible colitis phenotypes in recipient Il-10[-/-] mice. Engraftment of human-to-mouse FMT stochastically varied with individual transplantation events more than mouse-adapted FMT. Human-to-mouse FMT caused a population bottleneck with reassembly of microbiota composition that was host inflammatory environment specific. Mouse-adaptation in the inflamed Il-10[-/-] host reassembled a more aggressive microbiota that induced more severe colitis in serial transplant to Il-10[-/-] mice than the distinct microbiota reassembled in non-inflamed WT hosts.<br><br>CONCLUSIONS: Our findings support a model of IBD pathogenesis in which host inflammation promotes aggressive resident bacteria, which further drives a feed-forward process of dysbiosis exacerbated by gut inflammation. This model implies that effective management of IBD requires treating both the dysregulated host immune response and aggressive inflammation-driven microbiota. We propose that our mouse-adapted human microbiota model is an optimized, reproducible, and rigorous system to study human microbiome-driven disease phenotypes, which may be generalized to mouse models of other human microbiota-modulated diseases, including metabolic syndrome/obesity, diabetes, autoimmune diseases, and cancer. Video Abstract.}, }
@article {pmid39110597, year = {2024}, author = {Fu, Y and Yu, S and Li, J and Lao, Z and Yang, X and Lin, Z}, title = {DeepMineLys: Deep mining of phage lysins from human microbiome.}, journal = {Cell reports}, volume = {43}, number = {8}, pages = {114583}, doi = {10.1016/j.celrep.2024.114583}, pmid = {39110597}, issn = {2211-1247}, mesh = {Humans ; *Microbiota ; *Bacteriophages/genetics/metabolism ; Data Mining ; Viral Proteins/metabolism ; Neural Networks, Computer ; Animals ; Muramidase/metabolism ; Escherichia coli/genetics/metabolism ; }, abstract = {Vast shotgun metagenomics data remain an underutilized resource for novel enzymes. Artificial intelligence (AI) has increasingly been applied to protein mining, but its conventional performance evaluation is interpolative in nature, and these trained models often struggle to extrapolate effectively when challenged with unknown data. In this study, we present a framework (DeepMineLys [deep mining of phage lysins from human microbiome]) based on the convolutional neural network (CNN) to identify phage lysins from three human microbiome datasets. When validated with an independent dataset, our method achieved an F1-score of 84.00%, surpassing existing methods by 20.84%. We expressed 16 lysin candidates from the top 100 sequences in E. coli, confirming 11 as active. The best one displayed an activity 6.2-fold that of lysozyme derived from hen egg white, establishing it as the most potent lysin from the human microbiome. Our study also underscores several important issues when applying AI to biology questions. This framework should be applicable for mining other proteins.}, }
@article {pmid39109977, year = {2024}, author = {Xiao, Y and Louwies, T and Mars, RAT and Kashyap, PC}, title = {The Human Microbiome-A Physiologic Perspective.}, journal = {Comprehensive Physiology}, volume = {14}, number = {3}, pages = {5491-5519}, doi = {10.1002/cphy.c230013}, pmid = {39109977}, issn = {2040-4603}, mesh = {Humans ; *Microbiota/physiology ; Gastrointestinal Microbiome/physiology ; }, abstract = {The human microbiome consists of the microorganisms associated with the body, such as bacteria, fungi, archaea, protozoa, and viruses, along with their gene content and products. These microbes are abundant in the digestive, respiratory, renal/urinary, and reproductive systems. While microbes found in other organs/tissues are often associated with diseases, some reports suggest their presence even in healthy individuals. Lack of microbial colonization does not indicate a lack of microbial influence, as their metabolites can affect distant locations through circulation. In a healthy state, these microbes maintain a mutualistic relationship and help shape the host's physiological functions. Unlike the host's genetic content, microbial gene content and expression are dynamic and influenced by factors such as ethnicity, genetic background, sex, age, lifestyle/diet, and psychological/physical conditions. Therefore, defining a healthy microbiome becomes challenging as it is context dependent and can vary over time for an individual. Although differences in microbial composition have been observed in various diseases, these changes may reflect host alterations rather than causing the disease itself. As the field is evolving, there is increased emphasis on understanding when changes in the microbiome are an important component of pathogenesis rather than the consequence of a disease state. This article focuses on the microbial component in the digestive and respiratory tracts-the primary sites colonized by microorganisms-and the physiological functions of microbial metabolites in these systems. It also discusses their physiological functions in the central nervous and cardiovascular systems, which have no microorganism colonization under healthy conditions based on human studies. © 2024 American Physiological Society. Compr Physiol 14:5491-5519, 2024.}, }
@article {pmid39107044, year = {2025}, author = {Trepka, KR and Olson, CA and Upadhyay, V and Zhang, C and Turnbaugh, PJ}, title = {Pharma[e]cology: How the Gut Microbiome Contributes to Variations in Drug Response.}, journal = {Annual review of pharmacology and toxicology}, volume = {65}, number = {1}, pages = {355-373}, doi = {10.1146/annurev-pharmtox-022724-100847}, pmid = {39107044}, issn = {1545-4304}, mesh = {Humans ; *Gastrointestinal Microbiome/drug effects/physiology ; Animals ; Pharmaceutical Preparations/metabolism ; Neoplasms/drug therapy/microbiology ; Heart Diseases/drug therapy/microbiology ; Nervous System Diseases/drug therapy/microbiology ; }, abstract = {Drugs represent our first, and sometimes last, line of defense for many diseases, yet despite decades of research we still do not fully understand why a given drug works in one patient and fails in the next. The human gut microbiome is one of the missing puzzle pieces, due to its ability to parallel and extend host pathways for drug metabolism, along with more complex host-microbiome interactions. Herein, we focus on the well-established links between the gut microbiome and drugs for heart disease and cancer, plus emerging data on neurological disease. We highlight the interdisciplinary methods that are available and how they can be used to address major remaining knowledge gaps, including the consequences of microbial drug metabolism for treatment outcomes. Continued progress in this area promises fundamental biological insights into humans and their associated microbial communities and strategies for leveraging the microbiome to improve the practice of medicine.}, }
@article {pmid39102545, year = {2024}, author = {Duncan, RP and Moustafa, DA and Lewin, GR and Diggle, FL and Bomberger, JM and Whiteley, M and Goldberg, JB}, title = {Improvement of a mouse infection model to capture Pseudomonas aeruginosa chronic physiology in cystic fibrosis.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {121}, number = {33}, pages = {e2406234121}, pmid = {39102545}, issn = {1091-6490}, support = {K99 DE031018/DE/NIDCR NIH HHS/United States ; WHITELE20A0//Cystic Fibrosis Fouondation/ ; }, mesh = {*Cystic Fibrosis/microbiology/complications ; *Pseudomonas aeruginosa/physiology/pathogenicity ; Animals ; *Pseudomonas Infections/microbiology ; Mice ; *Disease Models, Animal ; Humans ; Respiratory Tract Infections/microbiology ; Host-Pathogen Interactions ; Sputum/microbiology ; }, abstract = {Laboratory models are central to microbiology research, advancing the understanding of bacterial physiology by mimicking natural environments, from soil to the human microbiome. When studying host-bacteria interactions, animal models enable investigators to examine bacterial dynamics associated with a host, and in the case of human infections, animal models are necessary to translate basic research into clinical treatments. Efforts toward improving animal infection models are typically based on reproducing host genotypes/phenotypes and disease manifestations, leaving a gap in how well the physiology of microbes reflects their behavior in a human host. Understanding bacterial physiology is vital because it dictates host response and bacterial interactions with antimicrobials. Thus, our goal was to develop an animal model that accurately recapitulates bacterial physiology in human infection. The system we chose to model was a chronic Pseudomonas aeruginosa respiratory infection in cystic fibrosis (CF). To accomplish this goal, we leveraged a framework that we recently developed to evaluate model accuracy by calculating the percentage of bacterial genes that are expressed similarly in a model to how they are expressed in their infection environment. We combined two complementary models of P. aeruginosa infection-an in vitro synthetic CF sputum model (SCFM2) and a mouse acute pneumonia model. This combined model captured the chronic physiology of P. aeruginosa in CF better than the standard mouse infection model, showing the power of a data-driven approach to refining animal models. In addition, the results of this work challenge the assumption that a chronic infection model requires long-term colonization.}, }
@article {pmid39101047, year = {2024}, author = {Liu, J and Zhang, X and Lin, T and Chen, R and Zhong, Y and Chen, T and Wu, T and Liu, C and Huang, A and Nguyen, TT and Lee, EE and Jeste, DV and Tu, XM}, title = {A New Paradigm for High-dimensional Data: Distance-Based Semiparametric Feature Aggregation Framework via Between-Subject Attributes.}, journal = {Scandinavian journal of statistics, theory and applications}, volume = {51}, number = {2}, pages = {672-696}, pmid = {39101047}, issn = {0303-6898}, support = {K23 MH118435/MH/NIMH NIH HHS/United States ; K23 MH119375/MH/NIMH NIH HHS/United States ; R01 MH094151/MH/NIMH NIH HHS/United States ; }, abstract = {This article proposes a distance-based framework incentivized by the paradigm shift towards feature aggregation for high-dimensional data, which does not rely on the sparse-feature assumption or the permutation-based inference. Focusing on distance-based outcomes that preserve information without truncating any features, a class of semiparametric regression has been developed, which encapsulates multiple sources of high-dimensional variables using pairwise outcomes of between-subject attributes. Further, we propose a strategy to address the interlocking correlations among pairs via the U-statistics-based estimating equations (UGEE), which correspond to their unique efficient influence function (EIF). Hence, the resulting semiparametric estimators are robust to distributional misspecification while enjoying root-n consistency and asymptotic optimality to facilitate inference. In essence, the proposed approach not only circumvents information loss due to feature selection but also improves the model's interpretability and computational feasibility. Simulation studies and applications to the human microbiome and wearables data are provided, where the feature dimensions are tens of thousands.}, }
@article {pmid39100447, year = {2024}, author = {Kakkar, A and Kandwal, G and Nayak, T and Jaiswal, LK and Srivastava, A and Gupta, A}, title = {Engineered bacteriophages: A panacea against pathogenic and drug resistant bacteria.}, journal = {Heliyon}, volume = {10}, number = {14}, pages = {e34333}, pmid = {39100447}, issn = {2405-8440}, abstract = {Antimicrobial resistance (AMR) is a major global concern; antibiotics and other regular treatment methods have failed to overcome the increasing number of infectious diseases. Bacteriophages (phages) are viruses that specifically target/kill bacterial hosts without affecting other human microbiome. Phage therapy provides optimism in the current global healthcare scenario with a long history of its applications in humans that has now reached various clinical trials. Phages in clinical trials have specific requirements of being exclusively lytic, free from toxic genes with an enhanced host range that adds an advantage to this requisite. This review explains in detail the various phage engineering methods and their potential applications in therapy. To make phages more efficient, engineering has been attempted using techniques like conventional homologous recombination, Bacteriophage Recombineering of Electroporated DNA (BRED), clustered regularly interspaced short palindromic repeats (CRISPR)-Cas, CRISPY-BRED/Bacteriophage Recombineering with Infectious Particles (BRIP), chemically accelerated viral evolution (CAVE), and phage genome rebooting. Phages are administered in cocktail form in combination with antibiotics, vaccines, and purified proteins, such as endolysins. Thus, phage therapy is proving to be a better alternative for treating life-threatening infections, with more specificity and fewer detrimental consequences.}, }
@article {pmid39092808, year = {2024}, author = {Jokela, R and Pärnänen, KM and Ponsero, AJ and Lahti, L and Kolho, KL and de Vos, WM and Salonen, A}, title = {A cohort study in family triads: impact of gut microbiota composition and early life exposures on intestinal resistome during the first two years of life.}, journal = {Gut microbes}, volume = {16}, number = {1}, pages = {2383746}, pmid = {39092808}, issn = {1949-0984}, mesh = {Humans ; *Gastrointestinal Microbiome/drug effects/genetics ; Infant ; Female ; *Feces/microbiology ; Male ; Cohort Studies ; *Anti-Bacterial Agents/pharmacology ; *Bacteria/genetics/classification/drug effects/isolation &amp; purification ; Infant, Newborn ; Bacteroides/genetics/drug effects/growth &amp; development ; Child, Preschool ; Metagenome ; Drug Resistance, Bacterial/genetics ; }, abstract = {Antibiotic resistance genes (ARGs) are prevalent in the infant gut microbiota and make up the intestinal resistome, representing a community ARG reservoir. This study focuses on the dynamics and persistence of ARGs in the early gut microbiota, and the effect of early exposures therein. We leveraged 2,328 stool metagenomes from 475 children in the HELMi cohort and the available parental samples to study the diversity, dynamics, and intra-familial sharing of the resistome during the first two years of life. We found higher within-family similarity of the gut resistome composition and ARG load in infant-mother pairs, and between spouses, but not in father-infant pairs. Early gut microbiota composition and development correlated with the ARG load; Bacteroides correlated positively and Bifidobacterium negatively with the load, reflecting the typical resistance levels in these taxa. Caesarean delivered infants harbored lower ARG loads, partly reflecting the scarcity of Bacteroides compared to vaginally delivered. Exposure to intrapartum or post-natal antibiotics showed only modest associations with the ARG load and composition, mainly before 12 months. Our results indicate that the resistome is strongly driven by the normal development of the microbiota in early life, and suggest importance of longer evolution of ARGs over effects of recent antibiotic exposure.}, }
@article {pmid39086645, year = {2024}, author = {Xie, S and Meng, Q and Wang, L}, title = {The effect of gut microbiome and plasma metabolome on systemic sclerosis: a bidirectional two-sample Mendelian randomization study.}, journal = {Frontiers in microbiology}, volume = {15}, number = {}, pages = {1427195}, pmid = {39086645}, issn = {1664-302X}, abstract = {BACKGROUND: Cellular and molecular biology, combined with research on the human microbiome and metabolome, have provided new insights into the pathogenesis of systemic sclerosis (SSc). However, most studies on gut microbiota (GM) and metabolome in SSc are observational studies. The impact of confounding factors and reverse causation leads to different insights. To shed light on this matter, we utilized Mendelian randomization (MR) to determine the causal effect of GM/metabolites on SSc.<br><br>METHODS: Based on summary-level data from genome-wide association studies, bidirectional Two-sample MR was conducted involving 196 GM, 1400 plasma metabolism, and 9,095 SSc. Inverse Variance Weighting (IVW) was mainly used for effect estimation.<br><br>RESULTS: Forward MR analysis found that three GM and two plasma metabolites are causally related to SSc. IVW results showed Victivallaceae (family) (OR, 1.469; 95%CI, 1.099-1.963; p&#x2009;=&#x2009;0.009) and LachnospiraceaeUCG004 (genus) (OR, 1.548; 95%CI, 1.020-2.349; p&#x2009;=&#x2009;0.04) were risk factor of SSc. Conversely, Prevotella7 (genus) (OR, 0.759; 95%CI, 0.578-0.997; p&#x2009;=&#x2009;0.048)was a protective factor of SSc. The results on plasma metabolites indicated that Pregnenediol disulfate (C21H34O8S2) levels (OR, 1.164; 95%CI, 1.006-1.347; p&#x2009;=&#x2009;0.041)was a risk factor of SSc, while Sphingomyelin (d18:1/19:0, d19:1/18:0) levels (OR, 0.821; 95%CI, 0.677-0.996; p&#x2009;=&#x2009;0.045)was a protective factor of SSc. Reverse MR analysis did not find causally relationship between SSc and the above GM/plasma metabolites.<br><br>CONCLUSION: Our results revealed the causally effect between GM/plasma metabolites and SSc. These findings provided new insights into the mechanism of SSc. In particular, we demonstrated Prevotella7 was a protective factor of SSc despite its controversial role in SSc in previous researches.}, }
@article {pmid39085612, year = {2024}, author = {Roje, B and Zhang, B and Mastrorilli, E and Kovačić, A and Sušak, L and Ljubenkov, I and Ćosić, E and Vilović, K and Meštrović, A and Vukovac, EL and Bučević-Popović, V and Puljiz, &#x17d; and Karaman, I and Terzić, J and Zimmermann, M}, title = {Gut microbiota carcinogen metabolism causes distal tissue tumours.}, journal = {Nature}, volume = {632}, number = {8027}, pages = {1137-1144}, pmid = {39085612}, issn = {1476-4687}, mesh = {Animals ; Female ; Humans ; Male ; Mice ; Biotransformation ; *Carcinogenesis/chemically induced/metabolism/pathology ; *Carcinogens/chemistry/metabolism/pharmacokinetics/toxicity ; *Gastrointestinal Microbiome/physiology ; Germ-Free Life ; Mice, Inbred C57BL ; *Nitrosamines/chemistry/metabolism/pharmacokinetics/toxicity ; *Urinary Bladder Neoplasms/chemically induced/etiology/metabolism/pathology/prevention &amp; control ; Disease Susceptibility ; }, abstract = {Exposure to environmental pollutants and human microbiome composition are important predisposition factors for tumour development[1,2]. Similar to drug molecules, pollutants are typically metabolized in the body, which can change their carcinogenic potential and affect tissue distribution through altered toxicokinetics[3]. Although recent studies demonstrated that human-associated microorganisms can chemically convert a wide range of xenobiotics and influence the profile and tissue exposure of resulting metabolites[4,5], the effect of microbial biotransformation on chemical-induced tumour development remains unclear. Here we show that the depletion of the gut microbiota affects the toxicokinetics of nitrosamines, which markedly reduces the development and severity of nitrosamine-induced urinary bladder cancer in mice[6,7]. We causally linked this carcinogen biotransformation to specific gut bacterial isolates in vitro and in vivo using individualized bacterial culture collections and gnotobiotic mouse models, respectively. We tested gut communities from different human donors to demonstrate that microbial carcinogen metabolism varies between individuals and we showed that this metabolic activity applies to structurally related nitrosamine carcinogens. Altogether, these results indicate that gut microbiota carcinogen metabolism may be a contributing factor for chemical-induced carcinogenesis, which could open avenues to target the microbiome for improved predisposition risk assessment and prevention of cancer.}, }
@article {pmid39073834, year = {2024}, author = {Scheperjans, F and Levo, R and Bosch, B and Lääperi, M and Pereira, PAB and Smolander, OP and Aho, VTE and Vetkas, N and Toivio, L and Kainulainen, V and Fedorova, TD and Lahtinen, P and Ortiz, R and Kaasinen, V and Satokari, R and Arkkila, P}, title = {Fecal Microbiota Transplantation for Treatment of Parkinson Disease: A Randomized Clinical Trial.}, journal = {JAMA neurology}, volume = {81}, number = {9}, pages = {925-938}, pmid = {39073834}, issn = {2168-6157}, mesh = {Humans ; *Parkinson Disease/therapy ; Middle Aged ; Male ; *Fecal Microbiota Transplantation/methods ; Female ; Aged ; Double-Blind Method ; Adult ; Treatment Outcome ; Dysbiosis/therapy ; }, abstract = {IMPORTANCE: Dysbiosis has been robustly demonstrated in Parkinson disease (PD), and fecal microbiota transplantation (FMT) has shown promising effects in preclinical PD models.<br><br>OBJECTIVE: To assess the safety and symptomatic efficacy of colonic single-dose anaerobically prepared FMT.<br><br>This was a double-blind, placebo-controlled, randomized clinical trial conducted between November 2020 and June 2023 with a follow-up period of 12 months at 4 hospitals in Finland. Patients with PD aged 35 to 75 years in Hoehn &amp; Yahr stage 1-3 with a mild to moderate symptom burden and dysbiosis of fecal microbiota were included. Of 229 patients screened, 48 were randomized and 47 received the intervention. One patient discontinued due to worsening of PD symptoms. Two further patients were excluded before analysis and 45 were included in the intention-to-treat analysis.<br><br>INTERVENTION: Participants were randomized in a 2:1 ratio to receive FMT or placebo via colonoscopy.<br><br>MAIN OUTCOMES AND MEASURES: The primary end point was the change of Movement Disorder Society Unified Parkinson's Disease Rating Scale parts I-III (part III off medication) at 6 months. Safety was assessed by recording adverse events (AEs).<br><br>RESULTS: The median (IQR) age was 65 (52.5-70.0) years in the placebo group and 66 (59.25-69.75) years in the FMT group; 9 (60.0%) and 16 (53.3%) patients were male in the placebo group and the FMT group, respectively. The primary outcome did not differ between the groups (0.97 points, 95% CI, -5.10 to 7.03, P&#x2009;=&#x2009;.75). Gastrointestinal AEs were more frequent in the FMT group (16 [53%] vs 1 [7%]; P&#x2009;=&#x2009;.003). Secondary outcomes and post hoc analyses showed stronger increase of dopaminergic medication and improvement of certain motor and nonmotor outcomes in the placebo group. Microbiota changes were more pronounced after FMT but differed by donor. Nevertheless, dysbiosis status was reversed more frequently in the placebo group.<br><br>CONCLUSIONS AND RELEVANCE: FMT was safe but did not offer clinically meaningful improvements. Further studies-for example, through modified FMT approaches or bowel cleansing-are warranted regarding the specific impact of donor microbiota composition and dysbiosis conversion on motor and nonmotor outcomes as well as medication needs in PD.<br><br>TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04854291.}, }
@article {pmid39069614, year = {2024}, author = {Dwaraka, VB and Aronica, L and Carreras-Gallo, N and Robinson, JL and Hennings, T and Carter, MM and Corley, MJ and Lin, A and Turner, L and Smith, R and Mendez, TL and Went, H and Ebel, ER and Sonnenburg, ED and Sonnenburg, JL and Gardner, CD}, title = {Unveiling the epigenetic impact of vegan vs. omnivorous diets on aging: insights from the Twins Nutrition Study (TwiNS).}, journal = {BMC medicine}, volume = {22}, number = {1}, pages = {301}, pmid = {39069614}, issn = {1741-7015}, mesh = {Humans ; *Epigenesis, Genetic ; *Diet, Vegan ; Female ; *DNA Methylation ; Male ; *Aging/genetics ; Middle Aged ; Aged ; Diet ; Twins/genetics ; Diet, Vegetarian ; }, abstract = {BACKGROUND: Geroscience focuses on interventions to mitigate molecular changes associated with aging. Lifestyle modifications, medications, and social factors influence the aging process, yet the complex molecular mechanisms require an in-depth exploration of the epigenetic landscape. The specific epigenetic clock and predictor effects of a vegan diet, compared to an omnivorous diet, remain underexplored despite potential impacts on aging-related outcomes.<br><br>METHODS: This study examined the impact of an entirely plant-based or healthy omnivorous diet over 8 weeks on blood DNA methylation in paired twins. Various measures of epigenetic age acceleration (PC GrimAge, PC PhenoAge, DunedinPACE) were assessed, along with system-specific effects (Inflammation, Heart, Hormone, Liver, and Metabolic). Methylation surrogates of clinical, metabolite, and protein markers were analyzed to observe diet-specific shifts.<br><br>RESULTS: Distinct responses were observed, with the vegan cohort exhibiting significant decreases in overall epigenetic age acceleration, aligning with anti-aging effects of plant-based diets. Diet-specific shifts were noted in the analysis of methylation surrogates, demonstrating the influence of diet on complex trait prediction through DNA methylation markers. An epigenome-wide analysis revealed differentially methylated loci specific to each diet, providing insights into the affected pathways.<br><br>CONCLUSIONS: This study suggests that a short-term vegan diet is associated with epigenetic age benefits and reduced calorie intake. The use of epigenetic biomarker proxies (EBPs) highlights their potential for assessing dietary impacts and facilitating personalized nutrition strategies for healthy aging. Future research should explore the long-term effects of vegan diets on epigenetic health and overall well-being, considering the importance of proper nutrient supplementation.<br><br>TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT05297825.}, }
@article {pmid39069097, year = {2024}, author = {Skolnick, S}, title = {Prospecting for para-endogenous anxiolytics in the human microbiome: Some promising pathways.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {244}, number = {}, pages = {173842}, doi = {10.1016/j.pbb.2024.173842}, pmid = {39069097}, issn = {1873-5177}, mesh = {Humans ; *Anti-Anxiety Agents/pharmacology/therapeutic use ; *Gastrointestinal Microbiome/drug effects ; Anxiety Disorders/drug therapy/microbiology/metabolism ; Pregnanolone/therapeutic use/pharmacology ; Animals ; Anxiety/drug therapy/microbiology ; }, abstract = {The gut microbiome is a vast, variable, and largely unexplored component of human biology that sits at the intersection of heritable and environmental factors, and represents a rich source of novel chemistry that is already known to be compatible with the human body. This alone would make it a promising place to search for new therapeutics, but recent work has also identified gut microbiome abnormalities in patients with a number of psychiatric disorders, including anxiety disorders-suggesting that not only treatments, but cures may lie therein. Here, we'll discuss two known "para-endogenous" anxiolytics-γ-hydroxybutyrate and the neurosteroid allopregnanolone-which have recently been discovered to be produced by the microbiome.}, }
@article {pmid39068184, year = {2024}, author = {de Jonge, PA and van den Born, BH and Zwinderman, AH and Nieuwdorp, M and Dutilh, BE and Herrema, H}, title = {Phylogeny and disease associations of a widespread and ancient intestinal bacteriophage lineage.}, journal = {Nature communications}, volume = {15}, number = {1}, pages = {6346}, pmid = {39068184}, issn = {2041-1723}, support = {955974//EC | Horizon 2020 Framework Programme (EU Framework Programme for Research and Innovation H2020)/ ; 955974//EC | Horizon 2020 Framework Programme (EU Framework Programme for Research and Innovation H2020)/ ; 0915018201002//ZonMw (Netherlands Organisation for Health Research and Development)/ ; 015.017.050//ZonMw (Netherlands Organisation for Health Research and Development)/ ; 390713860//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; 2019.82.004//Diabetes Fonds (Dutch Diabetes Research Foundation)/ ; }, mesh = {Humans ; *Phylogeny ; *Bacteriophages/genetics/isolation &amp; purification/classification ; *Gastrointestinal Microbiome/genetics ; Genome, Viral/genetics ; Metagenome/genetics ; Virome/genetics ; Inflammatory Bowel Diseases/virology ; Biodiversity ; Diabetes Mellitus, Type 2/virology ; Female ; Male ; Europe ; Netherlands ; Adult ; }, abstract = {Viruses are core components of the human microbiome, impacting health through interactions with gut bacteria and the immune system. Most human microbiome viruses are bacteriophages, which exclusively infect bacteria. Until recently, most gut virome studies focused on low taxonomic resolution (e.g., viral operational taxonomic units), hampering population-level analyses. We previously identified an expansive and widespread bacteriophage lineage in inhabitants of Amsterdam, the Netherlands. Here, we study their biodiversity and evolution in various human populations. Based on a phylogeny using sequences from six viral genome databases, we propose the Candidatus order Heliusvirales. We identify heliusviruses in 82% of 5441 individuals across 39 studies, and in nine metagenomes from humans that lived in Europe and North America between 1000 and 5000 years ago. We show that a large lineage started to diversify when Homo sapiens first appeared some 300,000 years ago. Ancient peoples and modern hunter-gatherers have distinct Ca. Heliusvirales populations with lower richness than modern urbanized people. Urbanized people suffering from type 1 and type 2 diabetes, as well as inflammatory bowel disease, have higher Ca. Heliusvirales richness than healthy controls. We thus conclude that these ancient core members of the human gut virome have thrived with increasingly westernized lifestyles.}, }
@article {pmid39066214, year = {2024}, author = {Alipour-Khezri, E and Skurnik, M and Zarrini, G}, title = {Pseudomonas aeruginosa Bacteriophages and Their Clinical Applications.}, journal = {Viruses}, volume = {16}, number = {7}, pages = {}, pmid = {39066214}, issn = {1999-4915}, mesh = {*Pseudomonas aeruginosa/virology ; Humans ; *Pseudomonas Infections/microbiology/therapy ; *Phage Therapy ; *Cystic Fibrosis/microbiology ; *Pseudomonas Phages/genetics/physiology ; Animals ; Bacteriophages/physiology/genetics ; Anti-Bacterial Agents/pharmacology/therapeutic use ; }, abstract = {Antimicrobial resistance poses a serious risk to contemporary healthcare since it reduces the number of bacterial illnesses that may be treated with antibiotics, particularly for patients with long-term conditions like cystic fibrosis (CF). People with a genetic predisposition to CF often have recurrent bacterial infections in their lungs due to a buildup of sticky mucus, necessitating long-term antibiotic treatment. Pseudomonas aeruginosa infections are a major cause of CF lung illness, and P. aeruginosa airway isolates are frequently resistant to many antibiotics. Bacteriophages (also known as phages), viruses that infect bacteria, are a viable substitute for antimicrobials to treat P. aeruginosa infections in individuals with CF. Here, we reviewed the utilization of P. aeruginosa bacteriophages both in vivo and in vitro, as well as in the treatment of illnesses and diseases, and the outcomes of the latter.}, }
@article {pmid39065154, year = {2024}, author = {Merra, G and Gualtieri, P and La Placa, G and Frank, G and Della Morte, D and De Lorenzo, A and Di Renzo, L}, title = {The Relationship between Exposome and Microbiome.}, journal = {Microorganisms}, volume = {12}, number = {7}, pages = {}, pmid = {39065154}, issn = {2076-2607}, abstract = {Currently, exposome studies include a raft of different monitoring tools, including remote sensors, smartphones, omics analyses, distributed lag models, etc. The similarity in structure between the exposome and the microbiota plus their functions led us to pose three pertinent questions from this viewpoint, looking at the actual relationship between the exposome and the microbiota. In terms of the exposome, a bistable equilibrium between health and disease depends on constantly dealing with an ever-changing totality of exposures that together shape an individual from conception to death. Regarding scientific knowledge, the exposome is still lagging in certain areas, like the importance of microorganisms in the equation. The human microbiome is defined as an aggregate assemblage of gut commensals that are hosted by our surfaces related to the external environment. Commensals' resistance to a variety of environmental exposures, such as antibiotic administration, confirms that a layer of these organisms is protected within the host. The exposome is a conceptual framework defined as the environmental component of the science-inspired systems ideology that shifts from a specificity-based medical approach to reasoning in terms of complexity. A parallel concept in population health research and precision public health is the human flourishing index, which aims to account for the numerous environmental factors that affect individual and population well-being beyond ambient pollution.}, }
@article {pmid39064765, year = {2024}, author = {Bui, TPN}, title = {The Human Microbiome as a Therapeutic Target for Metabolic Diseases.}, journal = {Nutrients}, volume = {16}, number = {14}, pages = {}, pmid = {39064765}, issn = {2072-6643}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology/drug effects ; *Metabolic Diseases/microbiology/therapy ; Symbiosis ; Dysbiosis ; Probiotics/therapeutic use ; Host Microbial Interactions/physiology ; }, abstract = {The human microbiome functions as a separate organ in a symbiotic relationship with the host. Disruption of this host-microbe symbiosis can lead to serious health problems. Modifications to the composition and function of the microbiome have been linked to changes in host metabolic outcomes. Industrial lifestyles with high consumption of processed foods, alcoholic beverages and antibiotic use have significantly altered the gut microbiome in unfavorable ways. Therefore, understanding the causal relationship between the human microbiome and host metabolism will provide important insights into how we can better intervene in metabolic health. In this review, I will discuss the potential use of the human microbiome as a therapeutic target to improve host metabolism.}, }
@article {pmid39063655, year = {2024}, author = {Mpakosi, A and Sokou, R and Theodoraki, M and Kaliouli-Antonopoulou, C}, title = {Neonatal Gut Mycobiome: Immunity, Diversity of Fungal Strains, and Individual and Non-Individual Factors.}, journal = {Life (Basel, Switzerland)}, volume = {14}, number = {7}, pages = {}, pmid = {39063655}, issn = {2075-1729}, abstract = {The human gastrointestinal ecosystem, or microbiome (comprising the total bacterial genome in an environment), plays a crucial role in influencing host physiology, immune function, metabolism, and the gut-brain axis. While bacteria, fungi, viruses, and archaea are all present in the gastrointestinal ecosystem, research on the human microbiome has predominantly focused on the bacterial component. The colonization of the human intestine by microbes during the first two years of life significantly impacts subsequent composition and diversity, influencing immune system development and long-term health. Early-life exposure to pathogens is crucial for establishing immunological memory and acquired immunity. Factors such as maternal health habits, delivery mode, and breastfeeding duration contribute to gut dysbiosis. Despite fungi's critical role in health, particularly for vulnerable newborns, research on the gut mycobiome in infants and children remains limited. Understanding early-life factors shaping the gut mycobiome and its interactions with other microbial communities is a significant research challenge. This review explores potential factors influencing the gut mycobiome, microbial kingdom interactions, and their connections to health outcomes from childhood to adulthood. We identify gaps in current knowledge and propose future research directions in this complex field.}, }
@article {pmid39061954, year = {2024}, author = {Zhao, Y and Li, C and Wu, K and Chen, H and Wang, Q and Xiao, Y and Yao, S and Hong, A and Zhang, M and Lei, S and Yang, W and Zhong, S and Umar, A and Huang, J and Yu, Z}, title = {Exploring the Impact of Short Term Travel on Gut Microbiota and Probiotic Bacteria Mediated Stability.}, journal = {Biomedicines}, volume = {12}, number = {7}, pages = {}, pmid = {39061954}, issn = {2227-9059}, support = {32170071//National Natural Science Foundation of China/ ; 32300051//National Natural Science Foundation of China/ ; 2023CXQD059//Central South University Innovation-Driven Research Programme/ ; }, abstract = {Although travelers are frequently accompanied by abdominal discomfort and even diarrhea, not every trip can cause this issue. Many studies have reported that intestinal microbes play an important role in it. However, little is known about the reason for the dynamics of these intestinal microbes. Here, we delved into the effects of short-term travel on the gut microbiota of 12 healthy individuals. A total of 72 fecal samples collected before and after one-week travel, alongside non-traveling controls, underwent amplicon sequencing and a series of bioinformatic analyses. We found that travel significantly increased intra-individual gut microbiota fluctuations without diarrhea symptoms. In addition, the initial composition of the gut microbiota before travel emerged as a crucial factor in understanding these fluctuations. Travelers with stable microbiota exhibited an enrichment of specific probiotic bacteria (Agathobaculum, Faecalibacterium, Bifidobacterium, Roseburia, Lactobacillus) before travel. Another batch of data validated their predictive role in distinguishing travelers with and without the gut microbial disorder. This work provided valuable insights into understanding the relationship between gut microbiota and travel. It offered a microbiota-centric perspective and a potential avenue for interventions to preserve gut health during travel.}, }
@article {pmid39061792, year = {2024}, author = {D'Ambrosio, A and Altomare, A and Boscarino, T and Gori, M and Balestrieri, P and Putignani, L and Del Chierico, F and Carotti, S and Cicala, M and Guarino, MPL and Piemonte, V}, title = {Mathematical Modeling of Vedolizumab Treatment's Effect on Microbiota and Intestinal Permeability in Inflammatory Bowel Disease Patients.}, journal = {Bioengineering (Basel, Switzerland)}, volume = {11}, number = {7}, pages = {}, pmid = {39061792}, issn = {2306-5354}, support = {N.A.//Takeda Italia S.p.A./ ; }, abstract = {Growing evidence suggests that impaired gut permeability and gut microbiota alterations are involved in the pathogenesis of Inflammatory Bowel Diseases (IBDs), which include Ulcerative Colitis (UC) and Crohn's Disease (CD). Vedolizumab is an anti-α4β7 antibody approved for IBD treatment, used as the first treatment or second-line therapy when the first line results in inadequate effectiveness. The aim of this study is to develop a mathematical model capable of describing the pathophysiological mechanisms of Vedolizumab treatment in IBD patients. In particular, the relationship between drug concentration in the blood, colonic mucosal permeability and fecal microbiota composition was investigated and modeled to detect and predict trends in order to support and tailor Vedolizumab therapies. To pursue this aim, clinical data from a pilot study on a cluster of 11 IBD patients were analyzed. Enrolled patients underwent colonoscopy in three phases (before (t0), after 24 weeks of (t1) and after 52 weeks of (t2) Vedolizumab treatment) to collect mucosal biopsies for transepithelial electrical resistance (TEER) evaluation (permeability to ions), intestinal permeability measurement and histological analysis. Moreover, fecal samples were collected for the intestinal microbiota analysis at the three time points. The collected data were compared to those of 11 healthy subjects at t0, who underwent colonoscopy for screening surveillance, and used to implement a three-compartmental mathematical model (comprising central blood, peripheral blood and the intestine). The latter extends previous evidence from the literature, based on the regression of experimental data, to link drug concentration in the peripheral blood compartment with Roseburia abundance and intestinal permeability. The clinical data showed that Vedolizumab treatment leads to an increase in TEER and a reduction in intestinal permeability to a paracellular probe, improving tissue inflammation status. Microbiota analysis showed increasing values of Roseburia, albeit not statistically significant. This trend was adequately reproduced by the mathematical model, which offers a useful tool to describe the pathophysiological effects of Vedolizumab therapy on colonic mucosal permeability and fecal microbiota composition. The model's satisfactory predictive capabilities and simplicity shed light on the relationship between the drug, the microbiota and permeability and allow for its straightforward extension to diverse therapeutic conditions.}, }
@article {pmid39053136, year = {2024}, author = {Gholamzad, A and Khakpour, N and Hashemi, SMA and Goudarzi, Y and Ahmadi, P and Gholamzad, M and Mohammadi, M and Hashemi, M}, title = {Exploring the virome: An integral part of human health and disease.}, journal = {Pathology, research and practice}, volume = {260}, number = {}, pages = {155466}, doi = {10.1016/j.prp.2024.155466}, pmid = {39053136}, issn = {1618-0631}, mesh = {Humans ; *Virome ; *Gastrointestinal Microbiome ; Inflammatory Bowel Diseases/virology ; }, abstract = {The human microbiome is a complex network of microorganisms that includes viruses, bacteria, and fungi. The gut virome is an essential component of the immune system, which is responsible for regulating the growth and responses of the host's immune system. The virome maintains a crucial role in the development of numerous diseases, including inflammatory bowel disease (IBD), Crohn's disease, and neurodegenerative disorders. The human virome has emerged as a promising biomarker and therapeutic target. This comprehensive review summarizes the present understanding of the virome and its implications in matters of health and disease, with a focus on the Human Microbiome Project.}, }
@article {pmid39043386, year = {2024}, author = {Duller, S and Moissl-Eichinger, C}, title = {Archaea in the Human Microbiome and Potential Effects on Human Infectious Disease.}, journal = {Emerging infectious diseases}, volume = {30}, number = {8}, pages = {1505-1513}, pmid = {39043386}, issn = {1080-6059}, mesh = {Humans ; *Archaea/genetics ; *Microbiota ; Communicable Diseases/microbiology ; }, abstract = {Archaea represent a separate domain of life, next to bacteria and eukarya. As components of the human microbiome, archaea have been associated with various diseases, including periodontitis, endodontic infections, small intestinal bacterial overgrowth, and urogenital tract infections. Archaea are generally considered nonpathogenic; the reasons are speculative because of limited knowledge and gene annotation challenges. Nevertheless, archaeal syntrophic principles that shape global microbial networks aid both archaea and potentially pathogenic bacteria. Evaluating archaea interactions remains challenging, requiring clinical studies on inflammatory potential and the effects of archaeal metabolism. Establishing a culture collection is crucial for investigating archaea functions within the human microbiome, which could improve health outcomes in infectious diseases. We summarize potential reasons for archaeal nonpathogenicity, assess the association with infectious diseases in humans, and discuss the necessary experimental steps to enable mechanistic studies involving archaea.}, }
@article {pmid39041015, year = {2024}, author = {Brame, JE and Liddicoat, C and Abbott, CA and Cando-Dumancela, C and Fickling, NW and Robinson, JM and Breed, MF}, title = {Urban sports fields support higher levels of soil butyrate and butyrate-producing bacteria than urban nature parks.}, journal = {Ecology and evolution}, volume = {14}, number = {7}, pages = {e70057}, pmid = {39041015}, issn = {2045-7758}, abstract = {Butyrate-producing bacteria colonise the gut of humans and non-human animals, where they produce butyrate, a short-chain fatty acid with known health benefits. Butyrate-producing bacteria also reside in soils and soil bacteria can drive the assembly of airborne bacterial communities (the aerobiome). Aerobiomes in urban greenspaces are important reservoirs of butyrate-producing bacteria as they supplement the human microbiome, but soil butyrate producer communities have rarely been examined in detail. Here, we studied soil metagenome taxonomic and functional profiles and soil physicochemical data from two urban greenspace types: sports fields (n = 11) and nature parks (n = 22). We also developed a novel method to quantify soil butyrate and characterised the in situ activity of butyrate-producing bacteria. We show that soil butyrate was higher in sports fields than nature parks and that sports fields also had significantly higher relative abundances of the terminal butyrate production genes buk and butCoAT than nature parks. Soil butyrate positively correlated with buk gene abundance (but not butCoAT). Soil moisture (r = .50), calcium (r = -.62), iron (ρ = .54), ammonium nitrogen (ρ = .58) and organic carbon (r = .45) had the strongest soil abiotic effects on soil butyrate concentrations and iron (ρ = .56) and calcium (ρ = -.57) had the strongest soil abiotic effects on buk read abundances. Overall, our findings contribute important new insights into the role of sports fields as key exposure reservoirs of butyrate producing bacteria, with important implications for the provision of microbiome-mediated human health benefits via butyrate.}, }
@article {pmid39040076, year = {2024}, author = {Onwuka, S and Bravo-Merodio, L and Gkoutos, GV and Acharjee, A}, title = {Explainable AI-prioritized plasma and fecal metabolites in inflammatory bowel disease and their dietary associations.}, journal = {iScience}, volume = {27}, number = {7}, pages = {110298}, pmid = {39040076}, issn = {2589-0042}, abstract = {Fecal metabolites effectively discriminate inflammatory bowel disease (IBD) and show differential associations with diet. Metabolomics and AI-based models, including explainable AI (XAI), play crucial roles in understanding IBD. Using datasets from the UK Biobank and the Human Microbiome Project Phase II IBD Multi'omics Database (HMP2 IBDMDB), this study uses multiple machine learning (ML) classifiers and Shapley additive explanations (SHAP)-based XAI to prioritize plasma and fecal metabolites and analyze their diet correlations. Key findings include the identification of discriminative metabolites like glycoprotein acetyl and albumin in plasma, as well as nicotinic acid metabolites andurobilin in feces. Fecal metabolites provided a more robust disease predictor model (AUC [95%]: 0.93 [0.87-0.99]) compared to plasma metabolites (AUC [95%]: 0.74 [0.69-0.79]), with stronger and more group-differential diet-metabolite associations in feces. The study validates known metabolite associations and highlights the impact of IBD on the interplay between gut microbial metabolites and diet.}, }
@article {pmid39031651, year = {2025}, author = {Liu, Y and Yang, H and Wang, P and Shi, Y and Shi, R and Zhang, S and Zhao, Y and Lan, J and Ge, S}, title = {Correlation between short-chain fatty acids and peri-implant disease: A cross-sectional study.}, journal = {Journal of periodontology}, volume = {96}, number = {1}, pages = {21-29}, doi = {10.1002/JPER.23-0682}, pmid = {39031651}, issn = {1943-3670}, support = {82100977//National Natural Science Foundation of China/ ; 2022LHM-KFKT004//Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research/ ; }, mesh = {Humans ; Male ; Cross-Sectional Studies ; Female ; *Fatty Acids, Volatile/analysis/metabolism ; Middle Aged ; *Peri-Implantitis/metabolism ; *Dental Implants ; Adult ; *Gingival Crevicular Fluid/chemistry ; Aged ; Acetic Acid ; Pentanoic Acids/analysis ; Formates/analysis ; Gas Chromatography-Mass Spectrometry ; Propionates ; Chromatography, High Pressure Liquid ; Stomatitis/metabolism ; Mucositis/metabolism ; Periodontal Index ; Lactic Acid/metabolism/analysis ; Hemiterpenes ; }, abstract = {BACKGROUND: To explore the correlation between short-chain fatty acids (SCFAs) in the peri-implant sulcular fluid (PISF) and peri-implant diseases.<br><br>METHODS: PISF samples were obtained from implants that have been placed for at least 5&#xa0;years, and peri-implant clinical parameters were examined. Gas chromatography-mass spectrometry and high-performance liquid chromatography were used to detect SCFAs in PISF. The correlation between SCFAs and clinical parameters was analyzed by Spearman's correlation. SCFAs related to peri-implant disease were identified by logistic regression and ranked by random forest analysis.<br><br>RESULTS: Eighty-six implants were divided into a peri-implant health group (PIH-group, 35 implants), peri-implant mucositis group (PIM-group, 25 implants), and peri-implantitis group (PI-group, 26 implants) according to clinical and radiographic examination results. The PIM-group had significantly lower formic acid detection rate than the other two groups (p&#xa0;<&#xa0;0.001). The PIM-group had significantly higher levels of acetic, propionic, and isovaleric acids than the PIH-group (p&#xa0;<&#xa0;0.05). The PI-group had significantly higher levels of propionic, butyric, isobutyric, valeric, and isovaleric acids than the PIH-group (p&#xa0;<&#xa0;0.05). The PI-group had significantly higher levels of butyric, isobutyric, and isovaleric acids than the PIM-group (p&#xa0;<&#xa0;0.05). SCFAs (apart from hexanoic and succinic acids) were significantly and positively correlated with clinical parameters (p&#xa0;<&#xa0;0.05). SCFAs related to peri-implant disease were ranked as follows: butyric, isovaleric, isobutyric, propionic, acetic, formic, and lactic acids.<br><br>CONCLUSIONS: Elevated specific SCFAs are correlated with peri-implant disease. Recognition of this correlation may help in early identification of peri-implant disease and guide further clinical interventions.}, }
@article {pmid39030525, year = {2024}, author = {Lu, L and Li, F and Gao, Y and Kang, S and Li, J and Guo, J}, title = {Microbiome in radiotherapy: an emerging approach to enhance treatment efficacy and reduce tissue injury.}, journal = {Molecular medicine (Cambridge, Mass.)}, volume = {30}, number = {1}, pages = {105}, pmid = {39030525}, issn = {1528-3658}, support = {31920210037//Fundamental Research Funds for Central Universities of the Central South University/ ; No. xbmuyjrc202217//Northwest Minzu University/ ; }, mesh = {Humans ; *Gastrointestinal Microbiome/radiation effects ; *Neoplasms/radiotherapy/microbiology/immunology/therapy ; *Probiotics/therapeutic use ; *Radiotherapy/adverse effects/methods ; Animals ; Microbiota/radiation effects ; Radiation Injuries/microbiology/therapy/etiology ; Treatment Outcome ; }, abstract = {Radiotherapy is a widely used cancer treatment that utilizes powerful radiation to destroy cancer cells and shrink tumors. While radiation can be beneficial, it can also harm the healthy tissues surrounding the tumor. Recent research indicates that the microbiota, the collection of microorganisms in our body, may play a role in influencing the effectiveness and side effects of radiation therapy. Studies have shown that specific species of bacteria living in the stomach can influence the immune system's response to radiation, potentially increasing the effectiveness of treatment. Additionally, the microbiota may contribute to adverse effects like radiation-induced diarrhea. A potential strategy to enhance radiotherapy outcomes and capitalize on the microbiome involves using probiotics. Probiotics are living microorganisms that offer health benefits when consumed in sufficient quantities. Several studies have indicated that probiotics have the potential to alter the composition of the gut microbiota, resulting in an enhanced immune response to radiation therapy and consequently improving the efficacy of the treatment. It is important to note that radiation can disrupt the natural balance of gut bacteria, resulting in increased intestinal permeability and inflammatory conditions. These disruptions can lead to adverse effects such as diarrhea and damage to the intestinal lining. The emerging field of radiotherapy microbiome research offers a promising avenue for optimizing cancer treatment outcomes. This paper aims to provide an overview of the human microbiome and its role in augmenting radiation effectiveness while minimizing damage.}, }
@article {pmid39030408, year = {2024}, author = {Gilbert, JA and Hartmann, EM}, title = {The indoors microbiome and human health.}, journal = {Nature reviews. Microbiology}, volume = {22}, number = {12}, pages = {742-755}, pmid = {39030408}, issn = {1740-1534}, mesh = {Humans ; *Microbiota ; Air Microbiology ; Air Pollution, Indoor ; Built Environment ; }, abstract = {Indoor environments serve as habitat for humans and are replete with various reservoirs and niches for microorganisms. Microorganisms enter indoor spaces with their human and non-human hosts, as well as via exchange with outdoor sources, such as ventilation and plumbing. Once inside, many microorganisms do not survive, especially on dry, barren surfaces. Even reduced, this microbial biomass has critical implications for the health of human occupants. As urbanization escalates, exploring the intersection of the indoor environment with the human microbiome and health is increasingly vital. The indoor microbiome, a complex ecosystem of microorganisms influenced by human activities and environmental factors, plays a pivotal role in modulating infectious diseases and fostering healthy immune development. Recent advancements in microbiome research shed light on this unique ecological system, highlighting the need for innovative approaches in creating health-promoting living spaces. In this Review, we explore the microbial ecology of built environments - places where humans spend most of their lives - and its implications for immune, endocrine and neurological health. We further propose strategies to harness the indoor microbiome for better health outcomes.}, }
@article {pmid39026867, year = {2024}, author = {Rudzite, M and O'Toole, GA}, title = {An energy coupling factor transporter of Streptococcus sanguinis impacts antibiotic susceptibility as well as metal and membrane homeostasis.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {39026867}, issn = {2692-8205}, support = {P30 CA023108/CA/NCI NIH HHS/United States ; R01 AI155424/AI/NIAID NIH HHS/United States ; }, abstract = {Streptococcus sanguinis is a prevalent member of human microbiome capable of acting as a causative agent of oral and respiratory infections. S. sanguinis competitive success within the infection niche is dependent on acquisition of metal ions and vitamins. Among the systems that bacteria use for micronutrient uptake is the energy coupling factor (ECF) transporter system EcfAAT. Here we describe physiological changes arising from EcfAAT transporter disruption. We found that EcfAAT contributes to S. sanguinis antibiotic sensitivity as well as metal and membrane homeostasis. Specifically, our work found that disruption of EcfAAT results in increased polymyxin susceptibility. We performed assessment of cell-associated metal content and found depletion of iron, magnesium, and manganese. Furthermore, membrane composition analysis revealed significant enrichment in unsaturated fatty acid species resulting in increased membrane fluidity. Our results demonstrate how disruption of a single EcfAAT transporter can have broad consequences on bacterial cell homeostasis. ECF transporters are of interest within the context of infection biology in bacterial species other than streptococci, hence work described here will further the understanding of how micronutrient uptake systems contribute to bacterial pathogenesis.}, }
@article {pmid39026688, year = {2024}, author = {Agnew, A and Humm, E and Zhou, K and Gunsalus, RP and Zhou, ZH}, title = {Reconstruction and identification of the native PLP synthase complex from Methanosarcina acetivorans lysate.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2024.07.09.602819}, pmid = {39026688}, issn = {2692-8205}, abstract = {Many protein-protein interactions behave differently in biochemically purified forms as compared to their in vivo states. As such, determining native protein structures may elucidate structural states previously unknown for even well-characterized proteins. Here we apply the bottom-up structural proteomics method, cryoID , toward a model methanogenic archaeon. While they are keystone organisms in the global carbon cycle and active members of the human microbiome, there is a general lack of characterization of methanogen enzyme structure and function. Through the cryoID approach, we successfully reconstructed and identified the native Methanosarcina acetivorans pyridoxal 5'-phosphate (PLP) synthase (PdxS) complex directly from cryogenic electron microscopy (cryoEM) images of fractionated cellular lysate. We found that the native PdxS complex exists as a homo-dodecamer of PdxS subunits, and the previously proposed supracomplex containing both the synthase (PdxS) and glutaminase (PdxT) was not observed in cellular lysate. Our structure shows that the native PdxS monomer fashions a single 8α/8β TIM-barrel domain, surrounded by seven additional helices to mediate solvent and interface contacts. A density is present at the active site in the cryoEM map and is interpreted as ribose 5-phosphate. In addition to being the first reconstruction of the PdxS enzyme from a heterogeneous cellular sample, our results reveal a departure from previously published archaeal PdxS crystal structures, lacking the 37 amino acid insertion present in these prior cases. This study demonstrates the potential of applying the cryoID workflow to capture native structural states at atomic resolution for archaeal systems, for which traditional biochemical sample preparation is nontrivial.}, }
@article {pmid39023173, year = {2024}, author = {Ivashkin, V and Maev, I and Poluektova, E and Sinitsa, A and Avalueva, E and Mnatsakanyan, M and Simanenkov, V and Karpeeva, J and Kopylova, D and Kuprina, I and Kucheryavyy, Y and Lapina, T and Solovyeva, O and Soom, M and Cheremushkina, N and Maevskaya, E and Maslennikov, R}, title = {Efficacy and Safety of Postbiotic Contained Inactivated Lactobacillus reuteri (Limosilactobacillus reuteri) DSM 17648 as Adjuvant Therapy in the Eradication of Helicobacter pylori in Adults With Functional Dyspepsia: A Randomized Double-Blind Placebo-Controlled Trial.}, journal = {Clinical and translational gastroenterology}, volume = {15}, number = {9}, pages = {e1}, pmid = {39023173}, issn = {2155-384X}, mesh = {Humans ; Double-Blind Method ; *Limosilactobacillus reuteri ; *Dyspepsia/microbiology/diagnosis/drug therapy/therapy ; Male ; Female ; *Helicobacter Infections/drug therapy/diagnosis/therapy/microbiology ; Adult ; *Helicobacter pylori/isolation &amp; purification ; *Probiotics/administration &amp; dosage/adverse effects/therapeutic use ; Middle Aged ; *Amoxicillin/administration &amp; dosage/adverse effects/therapeutic use ; *Clarithromycin/administration &amp; dosage/therapeutic use/adverse effects ; *Drug Therapy, Combination ; Treatment Outcome ; *Anti-Bacterial Agents/adverse effects/administration &amp; dosage/therapeutic use ; *Quality of Life ; Esomeprazole/administration &amp; dosage/adverse effects/therapeutic use ; Young Adult ; }, abstract = {INTRODUCTION: Increasing the effectiveness of eradication therapy is an important task in gastroenterology. The aim of this study was to evaluate the efficacy and safety of postbiotic containing inactivated (nonviable) Limosilactobacillus (Lactobacillus) reuteri DSM 17648 (Pylopass) as adjuvant treatment of Helicobacter pylori eradication in patients with functional dyspepsia (FD).<br><br>METHODS: This randomized, double-blind, placebo-controlled, multicenter, parallel study included H. pylori -positive patients with FD. The postbiotic group received Pylopass 200 mg bid for 14 days in combination with eradication therapy (esomeprazole 20 mg bid + amoxicillin 1,000 mg bid + clarithromycin 500 mg bid for 14 days) and another 14 days after the completion of eradication therapy. The study was registered in the ISRCTN registry (ISRCTN20716052).<br><br>RESULTS: Eradication efficiency was 96.7% for the postbiotic group vs 86.0% for the placebo group (P = 0.039). Both groups showed significant improvements in quality of life and reduction of most gastrointestinal symptoms with no significant differences between groups. The overall number of digestive adverse effects in the postbiotic group was lower than in the placebo group. Serious adverse effects were not registered.<br><br>DISCUSSION: The postbiotic containing inactivated L. reuteri DSM 17648 significantly improves the effectiveness of H. pylori eradication therapy in FD and decreases overall number of digestive adverse effects of this therapy.}, }
@article {pmid39022135, year = {2020}, author = {Jiang, J and Warren, CM and Browning, RL and Ciaccio, CE and Gupta, RS}, title = {Food allergy epidemiology and racial and/or ethnic differences.}, journal = {Journal of food allergy}, volume = {2}, number = {1}, pages = {11-16}, pmid = {39022135}, issn = {2689-0275}, abstract = {In recent decades, immunoglobulin E (IgE) mediated food allergy has become a growing public health concern. Converging evidence from cross-sectional prevalence studies, health care utilization records, and cohort studies indicate that food allergies are increasingly prevalent and often severe. Although IgE-mediated food allergy has long been considered a predominantly pediatric concern, analysis of recent self-reported data suggests that food allergies may be more prevalent among adult populations than previously acknowledged, with many reported cases of adult-onset allergies as well as persistent childhood-onset allergies. Results of studies also suggest that food allergy-related health care utilization is increasing as more individuals seek emergency treatment for food-induced anaphylaxis. Analysis of epidemiologic data also indicates that the burden of food allergies is unequally distributed. Published prevalence rates are highest in Western countries, e.g., the United States, United Kingdom, and Australia. Within these countries, there also is heterogeneity across racial and/or ethnic groups, with non-White and second-generation immigrant populations disproportionately affected. Importantly, such observations can shed light on the etiology of food allergy and inform improved clinical management, treatment, and prevention efforts. For example, there is a growing consensus that earlier introduction of allergenic foods, e.g., peanut, promotes oral tolerance and can dramatically reduce food allergy risk. In addition, much attention has been paid to the potentially deleterious effects of cutaneous allergen exposure, e.g., through eczematous skin, which can skew the immune response away from tolerance and toward allergic sensitization, thereby increasing food allergy risk. Furthermore, there is a growing appreciation for the potential protective effects of diverse microbial exposures, given mounting evidence for the immunomodulatory effects of the human microbiome. Also, when considering the geographic variability in the prevalence of certain food and environmental allergies as well as their structural similarities at the molecular level, it is believed that co-sensitization between food and environmental allergens may be a key driver of rising food allergy prevalence.}, }
@article {pmid39015605, year = {2024}, author = {Sermsaksasithorn, P and Asawanonda, P and Phutrakool, P and Ondee, T and Chariyavilaskul, P and Payungporn, S and Pongpirul, K and Hirankarn, N}, title = {Efficacy and Safety of Cannabis Transdermal Patch for Alleviating Psoriasis Symptoms: Protocol for a Randomized Controlled Trial (CanPatch).}, journal = {Medical cannabis and cannabinoids}, volume = {7}, number = {1}, pages = {99-110}, pmid = {39015605}, issn = {2504-3889}, abstract = {INTRODUCTION: Current topical treatments for psoriasis offer limited efficacy and are associated with long-term adverse effects in a subset of patients, highlighting the need for new therapeutic options. Cannabidiol (CBD), a non-psychoactive cannabinoid derived from Cannabis sativa L., has shown potential in reversing psoriasis pathology through its action on skin receptors in preclinical studies. Given the promising properties of CBD, transdermal patches containing this compound represent a novel approach to psoriasis treatment. However, comprehensive data on their efficacy and safety remain scarce.<br><br>METHODS: We outline a randomized, double-blind, placebo-controlled trial to assess the efficacy and safety of CBD transdermal patches with minimal tetrahydrocannabinol (THC) in 60 patients with mild to moderate plaque-type psoriasis at a university hospital in Thailand (n = 60). This study aims to evaluate the changes in the local psoriasis severity index (LPSI), itch score via a visual analog scale, and occurrence of adverse events on day 0, 30, 60, and 90 of the study. Additionally, we will examine the alteration in the skin, gut, and oral microbiome in a subset of participants to explore potential correlations with treatment outcomes. The primary outcome will focus on the difference in LPSI scores at the end of the study period, employing an intention-to-treat analysis. Multivariate logistic regression will be used to identify baseline clinical and microbiological predictors of treatment response.<br><br>CONCLUSION: This study aims to investigate the efficacy and safety of CBD transdermal patches in alleviating the symptoms of psoriasis. The results of this study may highlight a novel topical treatment option that reduces suffering in patients with psoriasis. We also designed to provide a holistic evaluation by considering both clinical outcomes and the underlying biological mechanisms, including the interaction with the human microbiome. Through this trial, we aim to contribute valuable insights into personalized psoriasis management strategies.}, }
@article {pmid39013264, year = {2024}, author = {Kim, J and Park, S and Kim, SJ and Yoo, I and Kim, H and Hwang, S and Sim, KM and Kim, I and Jun, E}, title = {High-throughput drug screening using a library of antibiotics targeting cancer cell lines that are resistant and sensitive to gemcitabine.}, journal = {Biochemical and biophysical research communications}, volume = {730}, number = {}, pages = {150369}, doi = {10.1016/j.bbrc.2024.150369}, pmid = {39013264}, issn = {1090-2104}, mesh = {*Gemcitabine ; *Deoxycytidine/analogs &amp; derivatives/pharmacology ; Humans ; *High-Throughput Screening Assays/methods ; *Drug Resistance, Neoplasm/drug effects ; Cell Line, Tumor ; *Anti-Bacterial Agents/pharmacology ; *Drug Screening Assays, Antitumor/methods ; Puromycin/pharmacology ; Antimetabolites, Antineoplastic/pharmacology ; Drug Synergism ; Antineoplastic Agents/pharmacology ; Small Molecule Libraries/pharmacology ; }, abstract = {Gemcitabine is a nucleoside analog widely used as an anticancer agent against several types of cancer. Although gemcitabine sometimes shows excellent effectiveness, cancer cells are often poorly responsive to or resistant to the drug. Recently, specific strains or dysbiosis of the human microbiome were correlated with drug reactivity and resistance acquisition. Therefore, we aimed to identify antibiotic compounds that can modulate the microbiome to enhance the responsiveness to gemcitabine. To achieve this, we confirmed the gemcitabine responsiveness based on public data and conducted drug screening on a set of 250 antibiotics compounds. Subsequently, we performed experiments to investigate whether the selected compounds could enhance the responsiveness to gemcitabine. First, we grouped a total of seven tumor cell lines into resistant and sensitive group based on the IC50 value (1 μM) of gemcitabine obtained from the public data. Second, we performed high-throughput screening with compound treatments, identifying seven compounds from the resistant group and five from the sensitive group based on dose dependency. Finally, the combination of the selected compound, puromycin dihydrochloride, with gemcitabine in gemcitabine-resistant cell lines resulted in extensive cell death and a significant increase in cytotoxic efficacy. Additionally, mRNA levels associated with cell viability and stemness were reduced. Through this study, we screened antibiotics to further improve the efficacy of existing anticancer drugs and overcome resistance. By combining existing anticancer agents and antibiotic substances, we hope to establish various drug combination therapies and ultimately improve cancer treatment efficacy.}, }
@article {pmid39011022, year = {2024}, author = {Sarkar, P and Chintaluri, S and Sarkar, S and Unnisa, M and Jakkampudi, A and Mulukutla, AP and Kumari, S and Reddy, DN and Talukdar, R}, title = {Evaluation of the Crosstalk Between the Host Mycobiome and Bacteriome in Patients with Chronic Pancreatitis.}, journal = {Indian journal of microbiology}, volume = {64}, number = {2}, pages = {603-617}, pmid = {39011022}, issn = {0046-8991}, abstract = {UNLABELLED: The human microbiome is a diverse consortium of microbial kingdoms that play pivotal roles in host health and diseases. We previously reported a dysbiotic bacteriome in chronic pancreatitis patients with diabetes (CPD) compared with patients with it's nondiabetic (CPND) phenotype. In this study, we extended our exploration to elucidate the intricate interactions between the mycobiome, bacteriome, and hosts' plasma metabolome with the disease phenotypes. A total of 25 participants (CPD, n = 7; CPND, n = 10; healthy control, n = 8) were recruited for the study. We observed elevated species richness in both the bacterial and fungal profiles within the CP diabetic cohort compared to the nondiabetic CP phenotype and healthy control cohorts. Notably, the CP group displayed heterogeneous fungal diversity, with only 40% of the CP nondiabetic patients and 20% of the CP diabetic patients exhibiting common core gut fungal profiles. Specific microbial taxa alterations were identified, including a reduction in Bifidobacterium adolescentis and an increase in the prevalence of Aspergillus penicilloides and Klebsiella sp. in the disease groups. In silico analysis revealed the enrichment of pathways related to lipopolysaccharide (LPS), apoptosis, and peptidase, as well as reduced counts of the genes responsible for carbohydrate metabolism in the CP groups. Additionally, distinct plasma metabolome signatures were observed, with CPD group exhibiting higher concentrations of sugars and glycerolipids, while the CPND cohort displayed elevated levels of amino acids in their blood. The fatty acid-binding protein (FABP) concentration was notably greater in the CPD group than in the HC group (4.220 vs. 1.10 ng/ml, p = 0.04). Furthermore, compared with healthy controls, disease groups exhibited fewer correlations between key fungal taxa (Aspergillus sp., Candida sp.) and bacterial taxa (Prevotella copri, Bifidobacteria sp., Rumminococcaceae). Our study unveils, for the first time, a dysbiotic mycobiome and emphasizes unique host bacterial-mycobial interactions in CP patient with diabetes, potentially influencing disease severity. These findings provide crucial insights for future mechanistic studies aiming to unravel the determinants of disease severity in this complex clinical context.<br><br>SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12088-024-01207-8.}, }
@article {pmid39009231, year = {2024}, author = {Réthi-Nagy, Z and Juhász, S}, title = {Microbiome's Universe: Impact on health, disease and cancer treatment.}, journal = {Journal of biotechnology}, volume = {392}, number = {}, pages = {161-179}, doi = {10.1016/j.jbiotec.2024.07.002}, pmid = {39009231}, issn = {1873-4863}, mesh = {Humans ; *Neoplasms/therapy/microbiology ; *Gastrointestinal Microbiome ; *Probiotics/therapeutic use ; *Fecal Microbiota Transplantation/methods ; Dysbiosis/microbiology/therapy ; Microbiota ; Animals ; }, abstract = {The human microbiome is a diverse ecosystem of microorganisms that reside in the body and influence various aspects of health and well-being. Recent advances in sequencing technology have brought to light microbial communities in organs and tissues that were previously considered sterile. The gut microbiota plays an important role in host physiology, including metabolic functions and immune modulation. Disruptions in the balance of the microbiome, known as dysbiosis, have been linked to diseases such as cancer, inflammatory bowel disease and metabolic disorders. In addition, the administration of antibiotics can lead to dysbiosis by disrupting the structure and function of the gut microbial community. Targeting strategies are the key to rebalancing the microbiome and fighting disease, including cancer, through interventions such as probiotics, fecal microbiota transplantation (FMT), and bacteria-based therapies. Future research must focus on understanding the complex interactions between diet, the microbiome and cancer in order to optimize personalized interventions. Multidisciplinary collaborations are essential if we are going to translate microbiome research into clinical practice. This will revolutionize approaches to cancer prevention and treatment.}, }
@article {pmid39006241, year = {2024}, author = {Hu, Y and Zhang, R and Li, J and Wang, H and Wang, M and Ren, Q and Fang, Y and Tian, L}, title = {Association Between Gut and Nasal Microbiota and Allergic Rhinitis: A Systematic Review.}, journal = {Journal of asthma and allergy}, volume = {17}, number = {}, pages = {633-651}, pmid = {39006241}, issn = {1178-6965}, abstract = {Allergic rhinitis is a chronic non-infectious inflammation of the nasal mucosa mediated by specific IgE. Recently, the human microbiome has drawn broad interest as a potential new target for treating this condition. This paper succinctly summarizes the main findings of 17 eligible studies published by February 2024, involving 1044 allergic rhinitis patients and 954 healthy controls from 5 countries. These studies examine differences in the human microbiome across important mucosal interfaces, including the nasal and intestinal areas, between patients and controls. Overall, findings suggest variations in the gut microbiota between allergic rhinitis patients and healthy individuals, although the specific bacterial taxa that significantly changed were not always consistent across studies. Due to the limited scope of existing research and patient coverage, the relationship between the nasal microbiome and allergic rhinitis remains inconclusive. The article discusses the potential immune-regulating role of the gut microbiome in allergic rhinitis. Further well-designed clinical trials with large-scale recruitment of allergic rhinitis patients are encouraged.}, }
@article {pmid39002973, year = {2024}, author = {Vich Vila, A and Zhang, J and Liu, M and Faber, KN and Weersma, RK}, title = {Untargeted faecal metabolomics for the discovery of biomarkers and treatment targets for inflammatory bowel diseases.}, journal = {Gut}, volume = {73}, number = {11}, pages = {1909-1920}, pmid = {39002973}, issn = {1468-3288}, mesh = {Humans ; *Inflammatory Bowel Diseases/metabolism ; *Metabolomics/methods ; *Feces/chemistry/microbiology ; *Biomarkers/metabolism/analysis ; *Gastrointestinal Microbiome/physiology ; Bile Acids and Salts/metabolism ; }, abstract = {The gut microbiome has been recognised as a key component in the pathogenesis of inflammatory bowel diseases (IBD), and the wide range of metabolites produced by gut bacteria are an important mechanism by which the human microbiome interacts with host immunity or host metabolism. High-throughput metabolomic profiling and novel computational approaches now allow for comprehensive assessment of thousands of metabolites in diverse biomaterials, including faecal samples. Several groups of metabolites, including short-chain fatty acids, tryptophan metabolites and bile acids, have been associated with IBD. In this Recent Advances article, we describe the contribution of metabolomics research to the field of IBD, with a focus on faecal metabolomics. We discuss the latest findings on the significance of these metabolites for IBD prognosis and therapeutic interventions and offer insights into the future directions of metabolomics research.}, }
@article {pmid38997154, year = {2024}, author = {Rysbekov, K and Abrakhmanova, S and Satybaeva, R and Starosvetova, Y and Kushugulova, A}, title = {Helicobacter pylori eradication therapy for children.}, journal = {Drug metabolism and personalized therapy}, volume = {39}, number = {2}, pages = {59-67}, pmid = {38997154}, issn = {2363-8915}, mesh = {Humans ; *Helicobacter Infections/drug therapy ; *Helicobacter pylori/drug effects/isolation &amp; purification ; Child ; Male ; Female ; *Drug Therapy, Combination ; *Anti-Bacterial Agents/administration &amp; dosage/therapeutic use ; *Vitamin D/administration &amp; dosage/blood ; Adolescent ; Treatment Outcome ; Proton Pump Inhibitors/administration &amp; dosage/therapeutic use ; Child, Preschool ; Amoxicillin/administration &amp; dosage/therapeutic use ; }, abstract = {OBJECTIVES: The research aims to investigate the effect of vitamin D supplementation on the efficacy of Helicobacter pylori eradication therapy and to find new drug combinations for the eradication of the bacterium.<br><br>METHODS: A total of 128 children participated in the research. They were distributed under the following criteria: group A were children who tested positive for H.&#xa0;pylori and were treated with the standard so-called triple therapy including vitamin D; group B were children who tested positive for H.&#xa0;pylori and received the standard triple therapy without including vitamin D in the treatment; and group C were children who tested negative for H.&#xa0;pylori. After endoscopic examination, additional venous blood samples were taken from the children to determine vitamin D levels. A controlled study was carried out 45&#xa0;days after the initial treatment.<br><br>RESULTS: The overall success rate of eradication therapy was 84.1&#x202f;%. In group A, the success rate of treatment was 93.5&#x202f;%, contrary to group B, where the success rate was 75&#x202f;%. Although there was a difference in the percentage of H.&#xa0;pylori eradication therapy in the main group compared to the control group, there was no significant difference in group B. The success rate of eradication is p=0.082.<br><br>CONCLUSIONS: Following the research results, the addition of vitamin D to the standard triple therapy regimen for H.&#xa0;pylori had no effect. It can therefore be concluded that vitamin D does not significantly increase the efficacy of eradication therapy.}, }
@article {pmid38996003, year = {2024}, author = {Byndloss, M and Devkota, S and Duca, F and Hendrik Niess, J and Nieuwdorp, M and Orho-Melander, M and Sanz, Y and Tremaroli, V and Zhao, L}, title = {The Gut Microbiota and Diabetes: Research, Translation, and Clinical Applications-2023 Diabetes, Diabetes Care, and Diabetologia Expert Forum.}, journal = {Diabetes care}, volume = {47}, number = {9}, pages = {1491-1508}, pmid = {38996003}, issn = {1935-5548}, support = {//Novo Nordisk/ ; R01 DK123446/DK/NIDDK NIH HHS/United States ; DP1 DK130687/DK/NIDDK NIH HHS/United States ; R01 DK131104/DK/NIDDK NIH HHS/United States ; P30 ES006694/ES/NIEHS NIH HHS/United States ; }, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Diabetes Mellitus, Type 2/microbiology ; Diabetes Mellitus/microbiology ; }, abstract = {This article summarizes the state of the science on the role of the gut microbiota (GM) in diabetes from a recent international expert forum organized by Diabetes, Diabetes Care, and Diabetologia, which was held at the European Association for the Study of Diabetes 2023 Annual Meeting in Hamburg, Germany. Forum participants included clinicians and basic scientists who are leading investigators in the field of the intestinal microbiome and metabolism. Their conclusions were as follows: 1) the GM may be involved in the pathophysiology of type 2 diabetes, as microbially produced metabolites associate both positively and negatively with the disease, and mechanistic links of GM functions (e.g., genes for butyrate production) with glucose metabolism have recently emerged through the use of Mendelian randomization in humans; 2) the highly individualized nature of the GM poses a major research obstacle, and large cohorts and a deep-sequencing metagenomic approach are required for robust assessments of associations and causation; 3) because single-time point sampling misses intraindividual GM dynamics, future studies with repeated measures within individuals are needed; and 4) much future research will be required to determine the applicability of this expanding knowledge to diabetes diagnosis and treatment, and novel technologies and improved computational tools will be important to achieve this goal.}, }
@article {pmid38992611, year = {2024}, author = {Chen, L and Li, Q and Huang, X and Li, Z}, title = {Association between sleep duration and possible sarcopenia in middle-aged and elderly Chinese individuals: evidence from the China health and retirement longitudinal study.}, journal = {BMC geriatrics}, volume = {24}, number = {1}, pages = {594}, pmid = {38992611}, issn = {1471-2318}, support = {2021B1515140026//The Guangdong Basic and Applied Basic Research Fund Local Incubation Projects/ ; 20211800904952//Dongguan City Social Science and Technology Development Project (Key)/ ; 202206010142//The Key Project of Guangzhou Science and Technology Program, China/ ; 2023B1212060018//The Science and Technology Planning Project of Guangdong Province, China/ ; }, mesh = {Aged ; Female ; Humans ; Male ; Middle Aged ; China/epidemiology ; East Asian People ; Longitudinal Studies ; Prevalence ; *Sarcopenia/epidemiology/diagnosis/physiopathology ; *Sleep Duration ; Time Factors ; }, abstract = {BACKGROUND: Sarcopenia is a common cause of disability in the aging population, and managing sarcopenia is an important step in building intrinsic capacity and promoting healthy aging. A growing body of evidence suggests that sleep deprivation may be a mediator of the development of sarcopenia. The purpose of this study was to explore the longitudinal association between sleep duration and possible sarcopenia using data from a national sample.<br><br>METHODS: Two waves of data from the CHARLS database for 2011 and 2015 were used in this study. All possible sarcopenia participants met the Asia Working Group for Sarcopenia 2019 (AWGS 2019) diagnostic criteria. Sleep duration was assessed using a self-report questionnaire, and sleep duration was categorized as short (&#x2264;&#x2009;6&#xa0;h), medium (6-8&#xa0;h), or long (>&#x2009;8&#xa0;h) based on previous studies. Longitudinal associations between sleep duration and possible sarcopenia will be calculated by univariate and multifactorial logistic regression analyses and expressed as odds ratios (ORs) and 95% confidence intervals (CIs).<br><br>RESULTS: A total of 5654 individuals participated in the follow-up study, with a prevalence of possible sarcopenia of 53.72% (578) in the short sleep duration group, 38.29% (412) in the medium sleep duration group, and 7.99% (86) in the long sleep duration group. According to the crude model of the second-wave follow-up study, short sleep durations were significantly more strongly associated with possible sarcopenia than were medium and long sleep durations (OR: 1.35, 95% CI: 1.17-1.55, P&#x2009;=&#x2009;0.000). The association between short sleep duration and possible sarcopenia was maintained even after adjustment for covariates such as age, gender, residence, education level, BMI, smoking status, alcohol consumption and comorbidities (OR: 1.18, 95% CI: 1.02-1.36, P&#x2009;=&#x2009;0.029). In the subgroup analysis, short sleep duration was associated with low grip strength (OR: 1.20, 95% CI: 1.02-1.41, P&#x2009;=&#x2009;0.031).<br><br>CONCLUSIONS: Sleep deprivation may be closely associated with the development of possible sarcopenia in middle-aged and elderly people, which provides new insights and ideas for sarcopenia intervention, and further studies are needed to reveal the underlying mechanisms involved.}, }
@article {pmid38987933, year = {2024}, author = {Zhao, Y and Bitzer, A and Power, JJ and Belikova, D and Torres Salazar, BO and Adolf, LA and Gerlach, D and Krismer, B and Heilbronner, S}, title = {Nasal commensals reduce Staphylococcus aureus proliferation by restricting siderophore availability.}, journal = {The ISME journal}, volume = {18}, number = {1}, pages = {}, pmid = {38987933}, issn = {1751-7370}, support = {TTU 08.708_00//German Center of Infection Research/ ; //Deutsche Forschungsgemeinschaft/ ; //German Research Foundation/ ; 2124-390838134/EXC-2124/1-05.002_0//Germany's Excellence Strategy-EXC/ ; 8180207//National Natural Science Foundation of China/ ; PRJNA1028639//NCBI/ ; }, mesh = {*Siderophores/metabolism ; *Staphylococcus aureus/metabolism/growth &amp; development ; Humans ; Animals ; *Staphylococcal Infections/microbiology ; Microbiota ; Mice ; Nasal Cavity/microbiology ; Iron/metabolism ; Symbiosis ; Microbial Interactions ; Bacteria/metabolism/classification/growth &amp; development ; Nose/microbiology ; }, abstract = {The human microbiome is critically associated with human health and disease. One aspect of this is that antibiotic-resistant opportunistic bacterial pathogens, such as methicillin-resistant Staphylococcus aureus, can reside within the nasal microbiota, which increases the risk of infection. Epidemiological studies of the nasal microbiome have revealed positive and negative correlations between non-pathogenic species and S. aureus, but the underlying molecular mechanisms remain poorly understood. The nasal cavity is iron-limited, and bacteria are known to produce iron-scavenging siderophores to proliferate in such environments. Siderophores are public goods that can be consumed by all members of a bacterial community. Accordingly, siderophores are known to mediate bacterial competition and collaboration, but their role in the nasal microbiome is unknown. Here, we show that siderophore acquisition is crucial for S. aureus nasal colonization in vivo. We screened 94 nasal bacterial strains from seven genera for their capacity to produce siderophores as well as to consume the siderophores produced by S. aureus. We found that 80% of the strains engaged in siderophore-mediated interactions with S. aureus. Non-pathogenic corynebacterial species were found to be prominent consumers of S. aureus siderophores. In co-culture experiments, consumption of siderophores by competitors reduced S. aureus growth in an iron-dependent fashion. Our data show a wide network of siderophore-mediated interactions between the species of the human nasal microbiome and provide mechanistic evidence for inter-species competition and collaboration impacting pathogen proliferation. This opens avenues for designing nasal probiotics to displace S. aureus from the nasal cavity of humans.}, }
@article {pmid38987811, year = {2024}, author = {Won, C and Yim, SS}, title = {Emerging methylation-based approaches in microbiome engineering.}, journal = {Biotechnology for biofuels and bioproducts}, volume = {17}, number = {1}, pages = {96}, pmid = {38987811}, issn = {2731-3654}, support = {G04220037//KAIST/ ; N10230105//KAIST/ ; N11230043//KAIST/ ; N10240028//KAIST/ ; N10240039//KAIST/ ; }, abstract = {Bacterial epigenetics, particularly through DNA methylation, exerts significant influence over various biological processes such as DNA replication, uptake, and gene regulation in bacteria. In this review, we explore recent advances in characterizing bacterial epigenomes, accompanied by emerging strategies that harness bacterial epigenetics to elucidate and engineer diverse bacterial species with precision and effectiveness. Furthermore, we delve into the potential of epigenetic modifications to steer microbial functions and influence community dynamics, offering promising opportunities for understanding and modulating microbiomes. Additionally, we investigate the extensive diversity of DNA methyltransferases and emphasize their potential utility in the context of the human microbiome. In summary, this review highlights the potential of DNA methylation as a powerful toolkit for engineering microbiomes.}, }
@article {pmid38979233, year = {2024}, author = {Dong, PT and Shi, W and He, X and Borisy, GG}, title = {Adhesive interactions within microbial consortia can be differentiated at the single-cell level through expansion microscopy.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {38979233}, issn = {2692-8205}, support = {R01 DE022586/DE/NIDCR NIH HHS/United States ; R01 DE023810/DE/NIDCR NIH HHS/United States ; R01 DE030943/DE/NIDCR NIH HHS/United States ; T90 DE026110/DE/NIDCR NIH HHS/United States ; }, abstract = {Investigating microbe-microbe interactions at the single-cell level is critical to unraveling the ecology and dynamics of microbial communities. In many situations, microbes assemble themselves into densely packed multi-species biofilms. The density and complexity pose acute difficulties for visualizing individual cells and analyzing their interactions. Here, we address this problem through an unconventional application of expansion microscopy, which allows for the 'decrowding' of individual bacterial cells within a multispecies community. Expansion microscopy generally has been carried out under isotropic expansion conditions and used as a resolution-enhancing method. In our variation of expansion microscopy, we carry out expansion under heterotropic conditions; that is, we expand the space between bacterial cells but not the space within individual cells. The separation of individual bacterial cells from each other reflects the competition between the expansion force pulling them apart and the adhesion force holding them together. We employed heterotropic expansion microscopy to study the relative strength of adhesion in model biofilm communities. These included mono and dual-species Streptococcus biofilms, and a three-species synthetic community (Fusobacterium nucleatum, Streptococcus mutans, and Streptococcus sanguinis) under conditions that facilitated interspecies coaggregation. Using adhesion mutants, we investigated the interplay between F. nucleatum outer membrane protein RadD and different Streptococcus species. We also examined the Schaalia-TM7 epibiont association. Quantitative proximity analysis was used to evaluate the separation of individual microbial members. Our study demonstrates that heterotropic expansion microscopy can 'decrowd' dense biofilm communities, improve visualization of individual bacterial members, and enable analysis of microbe-microbe adhesive interactions at the single-cell level.}, }
@article {pmid38977511, year = {2024}, author = {Rahim, MA and Seo, H and Kim, S and Barman, I and Ghorbanian, F and Hossain, MS and Shuvo, MSH and Lee, S and Song, HY}, title = {Exploring the potential of Lactocaseibacillus rhamnosus PMC203 in inducing autophagy to reduce the burden of Mycobacterium tuberculosis.}, journal = {Medical microbiology and immunology}, volume = {213}, number = {1}, pages = {14}, pmid = {38977511}, issn = {1432-1831}, support = {RS-2023-00219563//National Research Foundation of Korea/ ; Soonchunhyang University Research Fund//Soonchunhyang University/ ; 20018499//Korean Ministry of Trade, Industry, and Energy (MOTIE, Korea)/ ; }, mesh = {*Autophagy ; *Mycobacterium tuberculosis/genetics ; *Lacticaseibacillus rhamnosus/physiology/metabolism ; *Probiotics ; *Macrophages/microbiology ; Humans ; Lysosomes/metabolism ; Microtubule-Associated Proteins/metabolism/genetics ; Bacterial Load ; Tuberculosis/microbiology ; }, abstract = {Mycobacterium tuberculosis, a lethal pathogen in human history, causes millions of deaths annually, which demands the development of new concepts of drugs. Considering this fact, earlier research has explored the anti-tuberculosis potential of a probiotic strain, Lactocaseibacillus rhamnosus PMC203, leading to a subsequent focus on the molecular mechanism involved in its effect, particularly on autophagy. In this current study, immunoblotting-based assay exhibited a remarkable expression of autophagy marker LC3-II in the PMC203 treated group compared to an untreated group. A remarkable degradation of p62 was also noticed within treated cells compared to control. Furthermore, the immunofluorescence-based assay showed significant fold change in fluorescence intensity for alexa-647-LC3 and alexa-488-LC3, whereas p62 was degraded noticeably. Moreover, lysosomal biogenesis generation was elevated significantly in terms of LAMP1 and acidic vesicular organelles. As a result, PMC203-induced autophagy played a vital role in reducing M. tuberculosis burden within the macrophages in treated groups compared to untreated group. A colony -forming unit assay also revealed a significant reduction in M. tuberculosis in the treated cells over time. Additionally, the candidate strain significantly upregulated the expression of autophagy induction and lysosomal biogenesis genes. Together, these results could enrich our current knowledge of probiotics-mediated autophagy in tuberculosis and suggest its implications for innovatively managing tuberculosis.}, }
@article {pmid38974672, year = {2024}, author = {Castaño-Henao, L and Mendez, DFG and Egan, S and Sanabria, J}, title = {Changes in groundwater and surface water bacterial communities under disinfection processes: Chlorination, ozonization, photo-fenton and ultraviolet radiation.}, journal = {Current research in microbial sciences}, volume = {7}, number = {}, pages = {100244}, pmid = {38974672}, issn = {2666-5174}, abstract = {Pathogenic bacteria, introduced in water sources through faecal contamination, have traditionally been investigated as individual species, leading to the establishment of microbial, sanitary, and environmental quality indicators. Recent advancements in our understanding of the microbiome and its intricate interactions within the human-microbiome-environment network advocate for a broader evaluation of the impact of disinfection on the entire microbial community. In this study, we conducted a comprehensive screening experiment involving four disinfection processes; ozone, ultraviolet radiation with wavelengths between 200 - 280 nm (UV-C), photo-Fenton, and chlorination, applied to two distinct water sources; surface (SW) and groundwater (GW). The cells that remained viable after treatment were recovered using Brain Heart Infusion (BHI) broth, and 16S rRNA gene sequencing was used for their identification. Our findings confirmed the presence of faecal contamination in the water sources and revealed distinct effects of each treatment on the recovered bacterial populations. The chlorination of groundwater samples likely had a greater impact on bacteria in a vegetative state than on spores. Consequently, this led to a higher abundance in the BHI cultures of sporulating bacteria such as Bacillus (increasing from 0.36 to 93.62 %), while ozonation led to an elevated recovery of Pseudomonas (increasing from 45.2 to 69.9 %). Conversely, in surface water, calcium hypochlorite and ozone treatments favored the selection of Staphylococcus and Bacillus, whose relative abundance in the cultures increased from 0 to 39.22 % and from 0.35 to 96.6 %, respectively. In groundwater, Pseudomonas was resistant to UV-C radiation and their relative abundance increased from 45.2 % to 93.56 %, while photo-Fenton was effective against this bacterial group decreasing its relative abundance to 0.46 %. However, other genera such as Bacteroides, Aeromonas, and Citrobacter seemed to be less injured by this disinfection process. BHI broth was successful in recovering various bacterial groups that exhibited resistance to sublethal water disinfection.}, }
@article {pmid38967872, year = {2024}, author = {Lyytinen, OL and Dapuliga, C and Wallinger, D and Patpatia, S and Audu, BJ and Kiljunen, SJ}, title = {Three novel Enterobacter cloacae bacteriophages for therapeutic use from Ghanaian natural waters.}, journal = {Archives of virology}, volume = {169}, number = {8}, pages = {156}, pmid = {38967872}, issn = {1432-8798}, mesh = {*Enterobacter cloacae/virology/drug effects ; Ghana ; *Bacteriophages/genetics/isolation &amp; purification/physiology/classification ; *Anti-Bacterial Agents/pharmacology ; Phage Therapy/methods ; Genome, Viral ; Enterobacteriaceae Infections/therapy/microbiology ; Drug Resistance, Multiple, Bacterial ; Finland ; Humans ; Microbial Sensitivity Tests ; Ciprofloxacin/pharmacology ; Meropenem/pharmacology ; }, abstract = {Infections caused by multidrug-resistant (MDR) bacteria are a growing global concern. Enterobacter cloacae complex (ECC) species are particularly adept at developing antibiotic resistance. Phage therapy is proposed as an alternative treatment for pathogens that no longer respond to antibiotics. Unfortunately, ECC phages are understudied when compared to phages of many other bacterial species. In this Ghanaian-Finnish study, we isolated two ECC strains from ready-to-eat food samples and three novel phages from natural waters against these strains. We sequenced the genomic DNA of the novel Enterobacter phages, fGh-Ecl01, fGh-Ecl02, and fGh-Ecl04, and assessed their therapeutic potential. All of the phages were found to be lytic, easy to propagate, and lacking any toxic, integrase, or antibiotic resistance genes and were thus considered suitable for therapy purposes. They all were found to be related to T4-type viruses: fGh-Ecl01 and fGh-Ecl04 to karamviruses and fGh-Ecl02 to agtreviruses. Testing of Finnish clinical ECC strains showed promising susceptibility to these novel phages. As many as 61.1% of the strains were susceptible to fGh-Ecl01 and fGh-Ecl04, and 7.4% were susceptible to fGh-Ecl02. Finally, we investigated the susceptibility of the newly isolated ECC strains to three antibiotics - meropenem, ciprofloxacin, and cefepime - in combination with the novel phages. The use of phages and antibiotics together had synergistic effects. When using an antibiotic-phage combination, even low concentrations of antibiotics fully inhibited the growth of bacteria.}, }
@article {pmid38963518, year = {2024}, author = {Wang, B and Luan, J and Zhao, W and Yu, J and Li, A and Li, X and Zhong, X and Cao, H and Wang, R and Liu, B and Lu, S and Shi, M}, title = {Comprehensive multiomics analysis of the signatures of gastric mucosal bacteria and plasma metabolites across different stomach microhabitats in the development of gastric cancer.}, journal = {Cellular oncology (Dordrecht, Netherlands)}, volume = {}, number = {}, pages = {}, pmid = {38963518}, issn = {2211-3436}, support = {2021YFA0717002//National Key Research and Development Program of China/ ; 22-3-7-smjk-8-nsh//Funds for Qingdao Science and Technology Benefit People Demonstration Guide Special Project/ ; }, abstract = {PURPOSE: As an important component of the microenvironment, the gastric microbiota and its metabolites are associated with tumour occurrence, progression, and metastasis. However, the relationship between the gastric microbiota and the development of gastric cancer is unclear. The present study investigated the role of the gastric mucosa microbiome and metabolites as aetiological factors in gastric carcinogenesis.<br><br>METHODS: Gastric biopsies from different stomach microhabitats (n&#x2009;=&#x2009;70) were subjected to 16S rRNA gene sequencing, and blood samples (n&#x2009;=&#x2009;95) were subjected to untargeted metabolome (gas chromatography&#x2012;mass spectrometry, GC&#x2012;MS) analyses. The datasets were analysed using various bioinformatics approaches.<br><br>RESULTS: The microbiota diversity and community composition markedly changed during gastric carcinogenesis. High Helicobacter. pylori colonization modified the overall diversity and composition of the microbiota associated with gastritis and cancer in the stomach. Most importantly, analysis of the functional features of the microbiota revealed that nitrate reductase genes were significantly enriched in the tumoral microbiota, while urease-producing genes were significantly enriched in the microbiota of H. pylori-positive patients. A panel of 81 metabolites was constructed to discriminate gastric cancer patients from gastritis patients, and a panel of 15 metabolites was constructed to discriminate H. pylori-positive patients from H. pylori-negative patients. receiver operator characteristic (ROC) curve analysis identified a series of gastric microbes and plasma metabolites as potential biomarkers of gastric cancer.<br><br>CONCLUSION: The present study identified a series of signatures that may play important roles in gastric carcinogenesis and have the potential to be used as biomarkers for diagnosis and for the surveillance of gastric cancer patients with minimal invasiveness.}, }
@article {pmid38962127, year = {2024}, author = {Lange, E and Kranert, L and Krüger, J and Benndorf, D and Heyer, R}, title = {Microbiome modeling: a beginner's guide.}, journal = {Frontiers in microbiology}, volume = {15}, number = {}, pages = {1368377}, pmid = {38962127}, issn = {1664-302X}, abstract = {Microbiomes, comprised of diverse microbial species and viruses, play pivotal roles in human health, environmental processes, and biotechnological applications and interact with each other, their environment, and hosts via ecological interactions. Our understanding of microbiomes is still limited and hampered by their complexity. A concept improving this understanding is systems biology, which focuses on the holistic description of biological systems utilizing experimental and computational methods. An important set of such experimental methods are metaomics methods which analyze microbiomes and output lists of molecular features. These lists of data are integrated, interpreted, and compiled into computational microbiome models, to predict, optimize, and control microbiome behavior. There exists a gap in understanding between microbiologists and modelers/bioinformaticians, stemming from a lack of interdisciplinary knowledge. This knowledge gap hinders the establishment of computational models in microbiome analysis. This review aims to bridge this gap and is tailored for microbiologists, researchers new to microbiome modeling, and bioinformaticians. To achieve this goal, it provides an interdisciplinary overview of microbiome modeling, starting with fundamental knowledge of microbiomes, metaomics methods, common modeling formalisms, and how models facilitate microbiome control. It concludes with guidelines and repositories for modeling. Each section provides entry-level information, example applications, and important references, serving as a valuable resource for comprehending and navigating the complex landscape of microbiome research and modeling.}, }
@article {pmid38955124, year = {2024}, author = {Maryam,  and Rehman, MU and Hussain, I and Tayara, H and Chong, KT}, title = {A graph neural network approach for predicting drug susceptibility in the human microbiome.}, journal = {Computers in biology and medicine}, volume = {179}, number = {}, pages = {108729}, doi = {10.1016/j.compbiomed.2024.108729}, pmid = {38955124}, issn = {1879-0534}, mesh = {Humans ; *Gastrointestinal Microbiome/drug effects ; *Neural Networks, Computer ; Microbiota/drug effects ; Machine Learning ; Deep Learning ; }, abstract = {Recent studies have illuminated the critical role of the human microbiome in maintaining health and influencing the pharmacological responses of drugs. Clinical trials, encompassing approximately 150 drugs, have unveiled interactions with the gastrointestinal microbiome, resulting in the conversion of these drugs into inactive metabolites. It is imperative to explore the field of pharmacomicrobiomics during the early stages of drug discovery, prior to clinical trials. To achieve this, the utilization of machine learning and deep learning models is highly desirable. In this study, we have proposed graph-based neural network models, namely GCN, GAT, and GINCOV models, utilizing the SMILES dataset of drug microbiome. Our primary objective was to classify the susceptibility of drugs to depletion by gut microbiota. Our results indicate that the GINCOV surpassed the other models, achieving impressive performance metrics, with an accuracy of 93% on the test dataset. This proposed Graph Neural Network (GNN) model offers a rapid and efficient method for screening drugs susceptible to gut microbiota depletion and also encourages the improvement of patient-specific dosage responses and formulations.}, }
@article {pmid38951769, year = {2024}, author = {Ranta, K and Skurnik, M and Kiljunen, S}, title = {fENko-Kae01 is a flagellum-specific jumbo phage infecting Klebsiella aerogenes.}, journal = {BMC microbiology}, volume = {24}, number = {1}, pages = {234}, pmid = {38951769}, issn = {1471-2180}, mesh = {*Bacteriophages/genetics/classification/isolation &amp; purification/physiology ; *Genome, Viral ; *Flagella/virology/genetics ; *Enterobacter aerogenes/virology/genetics ; *Host Specificity ; Whole Genome Sequencing ; Myoviridae/genetics/isolation &amp; purification/classification/physiology ; }, abstract = {BACKGROUND: Klebsiella aerogenes is an opportunistic pathogen that causes a wide variety of infections. Due to the rising problem of antibiotic resistance, novel antibiotics and strategies to combat bacterial infections are needed. Host-specific bacteriophages are natural enemies of bacteria and can be used in phage therapy as an alternative form of treatment against bacterial infections. Jumbo phages are defined as phages with genomes larger than 200 kb. Relatively few studies have been done on jumbo phages compared to smaller phages.<br><br>RESULTS: A novel phage, fENko-Kae01, was isolated from a commercial phage cocktail. Genomic analysis revealed that fENko-Kae01 is a lytic jumbo phage with a 360&#xa0;kb genome encoding 578 predicted genes. No highly similar phage genomes were identified and fENko-Kae01 may be a completely new genus representative. No known genes associated with lysogenic life cycle, bacterial virulence, or antibiotic resistance were identified. The phage had myovirus morphology and a narrow host range. Phage resistant bacterial mutants emerged under phage selection. Whole genome sequencing revealed that the biogenesis of the flagellum was affected in four mutants and the lack of functional flagellum was confirmed in motility assays. Furthermore, phage fENKo-Kae01 failed to adsorb on the non-motile mutants indicating that the bacterial flagellum is the phage-binding receptor.<br><br>CONCLUSIONS: fENko-Kae01 is a novel jumbo bacteriophage that is considered safe for phage therapy. fENko-Kae01 uses the flagellum as the phage-binding receptor and may represent a completely novel genus.}, }
@article {pmid38950441, year = {2025}, author = {Chen, Y}, title = {Beyond Meta-Omics: Functional Genomics in Future Marine Microbiome Research.}, journal = {Annual review of marine science}, volume = {17}, number = {1}, pages = {577-592}, doi = {10.1146/annurev-marine-020123-100931}, pmid = {38950441}, issn = {1941-0611}, mesh = {*Microbiota ; *Genomics ; Oceans and Seas ; }, abstract = {When President Bill Clinton and Francis Collins, then the director of the National Human Genome Research Institute, celebrated the near completion of the human genome sequence at the White House in the summer of 2000, it is unlikely that they or anyone else could have predicted the blossoming of meta-omics in the following two decades and their applications in modern human microbiome and environmental microbiome research. This transformation was enabled by the development of high-throughput sequencing technologies and sophisticated computational biology tools and bioinformatics software packages. Today, environmental meta-omics has undoubtedly revolutionized our understanding of ocean ecosystems, providing the genetic blueprint of oceanic microscopic organisms. In this review, I discuss the importance of functional genomics in future marine microbiome research and advocate a position for a gene-centric, bottom-up approach in modern oceanography. I propose that a synthesis of multidimensional approaches is required for a better understanding of the true functionality of the marine microbiome.}, }
@article {pmid38948147, year = {2024}, author = {Guan, Y and Wu, D and Wang, H and Liu, NN}, title = {Microbiome-driven anticancer therapy: A step forward from natural products.}, journal = {mLife}, volume = {3}, number = {2}, pages = {219-230}, pmid = {38948147}, issn = {2770-100X}, abstract = {Human microbiomes, considered as a new emerging and enabling cancer hallmark, are increasingly recognized as critical effectors in cancer development and progression. Manipulation of microbiome revitalizing anticancer therapy from natural products shows promise toward improving cancer outcomes. Herein, we summarize our current understanding of the human microbiome-driven molecular mechanisms impacting cancer progression and anticancer therapy. We highlight the potential translational and clinical implications of natural products for cancer prevention and treatment by developing targeted therapeutic strategies as adjuvants for chemotherapy and immunotherapy against tumorigenesis. The challenges and opportunities for future investigations using modulation of the microbiome for cancer treatment are further discussed in this review.}, }
@article {pmid38945961, year = {2024}, author = {Kim, N and Ma, J and Kim, W and Kim, J and Belenky, P and Lee, I}, title = {Genome-resolved metagenomics: a game changer for microbiome medicine.}, journal = {Experimental &amp; molecular medicine}, volume = {56}, number = {7}, pages = {1501-1512}, pmid = {38945961}, issn = {2092-6413}, support = {R01 DK125382/DK/NIDDK NIH HHS/United States ; HI19C1344//Korea Health Industry Development Institute (KHIDI)/ ; }, mesh = {Humans ; *Metagenomics/methods ; *Metagenome ; *Microbiota/genetics ; Bacteria/genetics/classification ; Animals ; Genome, Bacterial ; Gastrointestinal Microbiome/genetics ; }, abstract = {Recent substantial evidence implicating commensal bacteria in human diseases has given rise to a new domain in biomedical research: microbiome medicine. This emerging field aims to understand and leverage the human microbiota and derivative molecules for disease prevention and treatment. Despite the complex and hierarchical organization of this ecosystem, most research over the years has relied on 16S amplicon sequencing, a legacy of bacterial phylogeny and taxonomy. Although advanced sequencing technologies have enabled cost-effective analysis of entire microbiota, translating the relatively short nucleotide information into the functional and taxonomic organization of the microbiome has posed challenges until recently. In the last decade, genome-resolved metagenomics, which aims to reconstruct microbial genomes directly from whole-metagenome sequencing data, has made significant strides and continues to unveil the mysteries of various human-associated microbial communities. There has been a rapid increase in the volume of whole metagenome sequencing data and in the compilation of novel metagenome-assembled genomes and protein sequences in public depositories. This review provides an overview of the capabilities and methods of genome-resolved metagenomics for studying the human microbiome, with a focus on investigating the prokaryotic microbiota of the human gut. Just as decoding the human genome and its variations marked the beginning of the genomic medicine era, unraveling the genomes of commensal microbes and their sequence variations is ushering us into the era of microbiome medicine. Genome-resolved metagenomics stands as a pivotal tool in this transition and can accelerate our journey toward achieving these scientific and medical milestones.}, }
@article {pmid38944815, year = {2024}, author = {Del Chierico, F and Masi, L and Petito, V and Baldelli, V and Puca, P and Benvenuto, R and Fidaleo, M and Palucci, I and Lopetuso, LR and Caristo, ME and Carrozza, C and Giustiniani, MC and Nakamichi, N and Kato, Y and Putignani, L and Gasbarrini, A and Pani, G and Scaldaferri, F}, title = {Solute Transporter OCTN1/Slc22a4 Affects Disease Severity and Response to Infliximab in Experimental Colitis: Role of Gut Microbiota and Immune Modulation.}, journal = {Inflammatory bowel diseases}, volume = {30}, number = {12}, pages = {2259-2270}, pmid = {38944815}, issn = {1536-4844}, support = {GR-2016-02364891//Italian Ministry of Health/ ; }, mesh = {Animals ; *Infliximab/therapeutic use ; Mice ; *Colitis/chemically induced/drug therapy/immunology/microbiology ; *Gastrointestinal Microbiome/drug effects ; *Mice, Knockout ; *Mice, Inbred C57BL ; *Disease Models, Animal ; *Dextran Sulfate ; *Organic Cation Transport Proteins/genetics ; Gastrointestinal Agents/pharmacology/therapeutic use ; Severity of Illness Index ; Symporters/genetics/metabolism ; Dysbiosis ; Immunity, Mucosal ; }, abstract = {BACKGROUND: Inflammatory bowel diseases are chronic disabling conditions with a complex and multifactorial etiology, still incompletely understood. OCTN1, an organic cation transporter, could have a role in modulating the inflammatory response, and some genetic polymorphisms of this molecule have been associated with increased risk of inflammatory bowel diseases. Until now, limited information exists on its potential in predicting/modulating patient's response to therapies. The aim of this study was to evaluate the role of OCTN1 in modifying gut microbiota and mucosal immunity in response to infliximab therapy in murine colitis.<br><br>METHODS: A dextran sodium sulphate model of colitis was used to assess the clinical efficacy of infliximab administered intravenously in ocnt1 gene knockout mice and their C57BL/6 controls. Stool, colon, and mesenteric lymph node samples were collected to evaluate differences in gut microbiota composition, histology, and T cell populations, respectively.<br><br>RESULTS: Octn1 -/- influences the microbiota profile and is associated with a worse dysbiosis in mice with colitis. Infliximab treatment attenuates colitis-associated dysbiosis, with an increase of bacterial richness and evenness in both strains. In comparison with wild type, octn1-/- mice have milder disease and a higher baseline percentage of Treg, Tmemory, Th2 and Th17 cells.<br><br>CONCLUSIONS: Our data support the murine model to study OCTN1 genetic contribution to inflammatory bowel diseases. This could be the first step towards the recognition of this membrane transporter as a biomarker in inflammatory conditions and a predictor of response to therapies.}, }
@article {pmid38942021, year = {2024}, author = {Chen, W and Li, Y and Wang, W and Gao, S and Hu, J and Xiang, B and Wu, D and Jiao, N and Xu, T and Zhi, M and Zhu, L and Zhu, R}, title = {Enhanced microbiota profiling in patients with quiescent Crohn's disease through comparison with paired healthy first-degree relatives.}, journal = {Cell reports. Medicine}, volume = {5}, number = {7}, pages = {101624}, pmid = {38942021}, issn = {2666-3791}, mesh = {Humans ; *Crohn Disease/microbiology/genetics ; Female ; Male ; Adult ; *Gastrointestinal Microbiome/genetics ; Feces/microbiology ; Family ; Middle Aged ; Case-Control Studies ; Fatty Acids, Volatile/metabolism ; Young Adult ; Metabolome ; Microbiota/genetics ; }, abstract = {Prior studies indicate no correlation between the gut microbes of healthy first-degree relatives (HFDRs) of patients with Crohn's disease (CD) and the development of CD. Here, we utilize HFDRs as controls to examine the microbiota and metabolome in individuals with active (CD-A) and quiescent (CD-R) CD, thereby minimizing the influence of genetic and environmental factors. When compared to non-relative controls, the use of HFDR controls identifies fewer differential taxa. Faecalibacterium, Dorea, and Fusicatenibacter are decreased in CD-R, independent of inflammation, and correlated with fecal short-chain fatty acids (SCFAs). Validation with a large multi-center cohort confirms decreased Faecalibacterium and other SCFA-producing genera in CD-R. Classification models based on these genera distinguish CD from healthy individuals and demonstrate superior diagnostic power than models constructed with markers identified using unrelated controls. Furthermore, these markers exhibited limited discriminatory capabilities for other diseases. Finally, our results are validated across multiple cohorts, underscoring their robustness and potential for diagnostic and therapeutic applications.}, }
@article {pmid38935049, year = {2024}, author = {Bai, X and Nielsen, SD and Kunisaki, KM and Trøseid, M}, title = {Pulmonary comorbidities in people with HIV- the microbiome connection.}, journal = {Current opinion in HIV and AIDS}, volume = {19}, number = {5}, pages = {246-252}, doi = {10.1097/COH.0000000000000871}, pmid = {38935049}, issn = {1746-6318}, mesh = {Humans ; *HIV Infections/complications/microbiology/epidemiology ; *Microbiota ; *Comorbidity ; *Lung Diseases/microbiology/epidemiology/complications ; *Dysbiosis/microbiology ; Lung/microbiology/physiopathology ; }, abstract = {PURPOSE OF REVIEW: To report recent evidence on associations between human microbiome, particularly airway and gut, and pulmonary comorbidities in people with HIV (PWH). Furthermore, we explore how changes in the microbiome may contribute to pulmonary immune dysregulation and higher rates of pulmonary comorbidities among PWH. Finally, we propose future directions in the field.<br><br>RECENT FINDINGS: Increased risk of pulmonary comorbidities and rapid lung function decline have been reported in even well treated PWH. Altered microbiota profiles have been reported in PWH with pulmonary comorbidities and rapid lung function decline as compared to those without. The most consistent data have been the association between HIV-related pulmonary comorbidities, lung and oral microbiota dysbiosis, which has been also associated with distinct respiratory mucosal inflammatory profiles and short-term mortality. However, a possible causal link remains to be elucidated.<br><br>SUMMARY: Associations between the lung and oral microbiome, HIV-associated pulmonary comorbidities and rapid lung function decline have been reported in recent studies. Yet the underlying mechanism underpinning the observed associations is largely unknown and substantial knowledge gaps remain. Future research is warranted to unveil the role and mechanism of human microbiome from different anatomical compartments in relation to pulmonary comorbidities in PWH.}, }
@article {pmid38932188, year = {2024}, author = {Alipour-Khezri, E and Moqadami, A and Barzegar, A and Mahdavi, M and Skurnik, M and Zarrini, G}, title = {Bacteriophages and Green Synthesized Zinc Oxide Nanoparticles in Combination Are Efficient against Biofilm Formation of Pseudomonas aeruginosa.}, journal = {Viruses}, volume = {16}, number = {6}, pages = {}, pmid = {38932188}, issn = {1999-4915}, mesh = {*Zinc Oxide/pharmacology ; *Pseudomonas aeruginosa/virology/drug effects/physiology ; *Biofilms/drug effects ; *Metal Nanoparticles/chemistry ; Green Chemistry Technology ; Bacteriophages/physiology ; Anti-Bacterial Agents/pharmacology ; Nanoparticles/chemistry ; }, abstract = {Bacteriophages (phages) are viruses that infect the bacteria within which their reproduction cycle takes place, a process that ends in the lysis and death of the bacterial cell. Some phages are also able to destroy bacterial biofilms. Due to increased antibiotics resistance, Pseudomonas aeruginosa, another biofilm-forming pathogen, is a problem in many parts of the world. Zinc oxide (ZnO) and other metal nanoparticles (NPs) are biologically active and also possess anti-biofilm properties. ZnO-NPs were prepared by the green synthesis method using orange peels. The vibrational peaks of the ZnO-NPs were analyzed using FTIR analysis, and their size and morphological properties were determined using scanning electron microscopy (SEM). The ability of the ZnO-NPs to reduce or eliminate P. aeruginosa biofilm alone or in combination with phages PB10 and PA19 was investigated. The P. aeruginosa cells were effectively killed in the preformed 48 h biofilms during a 24 h incubation with the ZnO-NP-phage combination, in comparison with the control or ZnO-NPs alone. The treatments on growing biofilms were most efficient in the final stages of biofilm development. All five treatment groups showed a significant biofilm reduction compared to the control group (p < 0.0001) at 48 h of incubation. The influence of the ZnO-NPs and phages on the quorum sensing system of P. aeruginosa was monitored by quantitative real-time PCR (qRT-PCR) of the autoinducer biosynthesis gene lasI. While the ZnO-NPs repressed the lasI gene transcription, the phages slightly activated it at 24 and 48 h of incubation. Also, the effect of the ZnO-NPs and phage PA19 on the viability of HFF2 cells was investigated and the results showed that the combination of NPs with PA19 reduced the toxic effect of ZnO-NPs and also stimulated the growth in normal cells.}, }
@article {pmid38930571, year = {2024}, author = {Sprague, KL and Rajakaruna, S and Bandow, B and Burchat, N and Bottomley, M and Sampath, H and Paliy, O}, title = {Gut Microbiota Fermentation of Digested Almond-Psyllium-Flax Seed-Based Artisan Bread Promotes Mediterranean Diet-Resembling Microbial Community.}, journal = {Microorganisms}, volume = {12}, number = {6}, pages = {}, pmid = {38930571}, issn = {2076-2607}, support = {R01 DK126963/DK/NIDDK NIH HHS/United States ; DBI-1335772//National Science Foundation/ ; }, abstract = {Different modifications of the standard bread recipe have been proposed to improve its nutritional and health benefits. Here, we utilized the in vitro Human Gut Simulator (HGS) to assess the fermentation of one such artisan bread by human gut microbiota. Dried and milled bread, composed of almond flour, psyllium husks, and flax seeds as its three main ingredients, was first subjected to an in vitro protocol designed to mimic human oro-gastro-intestinal digestion. The bread digest was then supplied to complex human gut microbial communities, replacing the typical Western diet-based medium (WM) of the GHS system. Switching the medium from WM to bread digest resulted in statistically significant alterations in the community structure, encoded functions, produced short-chain fatty acids, and available antioxidants. The abundances of dietary fiber degraders Enterocloster, Mitsuokella, and Prevotella increased; levels of Gemmiger, Faecalibacterium, and Blautia decreased. These community alterations resembled the previously revealed differences in the distal gut microbiota of healthy human subjects consuming typical Mediterranean vs. Western-pattern diets. Therefore, the consumption of bread high in dietary fiber and unsaturated fatty acids might recapitulate the beneficial effects of the Mediterranean diet on the gut microbiota.}, }
@article {pmid38930451, year = {2024}, author = {Balleza-Alejandri, LR and Peña-Durán, E and Beltrán-Ramírez, A and Reynoso-Roa, AS and Sánchez-Abundis, LD and García-Galindo, JJ and Suárez-Rico, DO}, title = {Decoding the Gut Microbiota-Gestational Diabetes Link: Insights from the Last Seven Years.}, journal = {Microorganisms}, volume = {12}, number = {6}, pages = {}, pmid = {38930451}, issn = {2076-2607}, abstract = {The human microbiome, a complex ecosystem of bacteria, viruses, and protozoans living in symbiosis with the host, plays a crucial role in human health, influencing everything from metabolism to immune function. Dysbiosis, or an imbalance in this ecosystem, has been linked to various health issues, including diabetes and gestational diabetes (GD). In diabetes, dysbiosis affects the function of adipose tissue, leading to the release of adipokines and cytokines, which increase inflammation and insulin resistance. During pregnancy, changes to the microbiome can exacerbate glucose intolerance, a common feature of GD. Over the past years, burgeoning insights into the gut microbiota have unveiled its pivotal role in human health. This article comprehensively reviews literature from the last seven years, highlighting the association between gut microbiota dysbiosis and GD, as well as the metabolism of antidiabetic drugs and the potential influences of diet and probiotics. The underlying pathophysiological mechanisms discussed include the impact of dysbiosis on systemic inflammation and the interplay with genetic and environmental factors. By focusing on recent studies, the importance of considering microbial health in the prevention and treatment of GD is emphasized, providing insights into future research directions and clinical applications to improve maternal-infant health outcomes.}, }
@article {pmid38929681, year = {2024}, author = {Lee, J and Kim, H and Park, JS}, title = {Beyond the Bile: Exploring the Microbiome and Metabolites in Cholangiocarcinoma.}, journal = {Life (Basel, Switzerland)}, volume = {14}, number = {6}, pages = {}, pmid = {38929681}, issn = {2075-1729}, support = {N/A//INHA UNIVERSITY HOSPITAL Research Grant/ ; N/A//Shihwa medical center research fund/ ; }, abstract = {INTRODUCTION: Cholangiocarcinoma (CCC) still has a high mortality rate despite improvements in diagnostic and therapeutic techniques. The role of the human microbiome in CCC is poorly understood, and a recent metagenomic analysis demonstrated a significant correlation between microbiome-associated carcinogenesis and CCC. This study aimed to investigate changes in microbiome composition associated with CCC and its metabolic signature by integrating taxonomic and functional information with metabolomics data and in vitro experimental results.<br><br>METHODS: From February 2019 to January 2021, this study included patients who underwent endoscopic retrograde cholangiopancreatography (ERCP), both with and without a diagnosis of CCC. Bile samples were collected via endoscopic nasobiliary drainages (ENBD) and subjected to DNA extraction, PCR amplification of the bacterial 16S rRNA gene V3-V4 region, and data analysis using QIIME2. In vitro Carboxyfluorescein succinimidyl ester (CFSE) proliferation and Annexin V/PI apoptosis assays were performed to investigate the effects of metabolites on CCC cells.<br><br>RESULTS: A total of 24 patients were included in the study. Bile fluid analysis revealed a significantly higher abundance of Escherichia coli in the CCC group. Alpha diversity analyses exhibited significant differences between the CCC and non-CCC groups, and Nuclear Magnetic Resonance (NMR) spectroscopy metabolic profiling identified 15 metabolites with significant concentration differences; isoleucine showed the most notable difference. In vitro experiments demonstrated that isoleucine suppressed CCC cell proliferation but did not induce apoptosis.<br><br>CONCLUSIONS: This research underlines the significance of biliary dysbiosis and specific bile metabolites, such as isoleucine, in influencing the development and progression of CCC.}, }
@article {pmid38927134, year = {2024}, author = {Martins, D and Silva, C and Ferreira, AC and Dourado, S and Albuquerque, A and Saraiva, F and Batista, AB and Castro, P and Leite-Moreira, A and Barros, AS and Miranda, IM}, title = {Unravelling the Gut Microbiome Role in Cardiovascular Disease: A Systematic Review and a Meta-Analysis.}, journal = {Biomolecules}, volume = {14}, number = {6}, pages = {}, pmid = {38927134}, issn = {2218-273X}, support = {UIDB/00051/2020//Funda&#xe7;&#xe3;o para a Ci&#xea;ncia e Tecnologia/ ; UIDP/00051/2020//Funda&#xe7;&#xe3;o para a Ci&#xea;ncia e Tecnologia/ ; 2021.06947.BD//Funda&#xe7;&#xe3;o para a Ci&#xea;ncia e Tecnologia/ ; }, mesh = {*Gastrointestinal Microbiome ; Humans ; *Cardiovascular Diseases/microbiology/metabolism ; Bacteria/metabolism/classification/genetics ; Methylamines/metabolism/blood ; }, abstract = {A notable shift in understanding the human microbiome's influence on cardiovascular disease (CVD) is underway, although the causal association remains elusive. A systematic review and meta-analysis were conducted to synthesise current knowledge on microbial taxonomy and metabolite variations between healthy controls (HCs) and those with CVD. An extensive search encompassing three databases identified 67 relevant studies (2012-2023) covering CVD pathologies from 4707 reports. Metagenomic and metabolomic data, both qualitative and quantitative, were obtained. Analysis revealed substantial variability in microbial alpha and beta diversities. Moreover, specific changes in bacterial populations were shown, including increased Streptococcus and Proteobacteria and decreased Faecalibacterium in patients with CVD compared with HC. Additionally, elevated trimethylamine N-oxide levels were reported in CVD cases. Biochemical parameter analysis indicated increased fasting glucose and triglycerides and decreased total cholesterol and low- and high-density lipoprotein cholesterol levels in diseased individuals. This study revealed a significant relationship between certain bacterial species and CVD. Additionally, it has become clear that there are substantial inconsistencies in the methodologies employed and the reporting standards adhered to in various studies. Undoubtedly, standardising research methodologies and developing extensive guidelines for microbiome studies are crucial for advancing the field.}, }
@article {pmid38926732, year = {2024}, author = {Li, Q and Huang, Z and Yang, H and Tang, J and Zuo, T and Yang, Q and Huang, Z and Guo, Q and Li, M and Gao, X and Chao, K}, title = {Intestinal mRNA expression profiles associated with mucosal healing in ustekinumab-treated Crohn's disease patients: bioinformatics analysis and prospective cohort validation.}, journal = {Journal of translational medicine}, volume = {22}, number = {1}, pages = {595}, pmid = {38926732}, issn = {1479-5876}, support = {2022JBGS05//the Sixth Affiliated Hospital of Sun Yat-Sen University/ ; 2022JBGS03//the Sixth Affiliated Hospital of Sun Yat-Sen University/ ; 2020B1111170004//the program of Guangdong Provincial Clinical Research Center for Digestive Diseases/ ; 1010CG(2023)-12//the Sixth Affiliated Hospital of Sun Yat-Sen University Clinical Research-'1010' Program/ ; }, mesh = {Adult ; Female ; Humans ; Male ; Cluster Analysis ; *Computational Biology/methods ; *Crohn Disease/genetics/drug therapy ; Gene Expression Profiling ; Gene Ontology ; Intestinal Mucosa/metabolism/pathology ; Prospective Studies ; Reproducibility of Results ; *RNA, Messenger/genetics/metabolism ; ROC Curve ; Transcriptome/genetics ; *Ustekinumab/therapeutic use/pharmacology ; }, abstract = {BACKGROUND: Variations exist in the response of patients with Crohn's disease (CD) to ustekinumab (UST) treatment, but the underlying cause remains unknown. Our objective was to investigate the involvement of immune cells and identify potential biomarkers that could predict the response to interleukin (IL) 12/23 inhibitors in patients with CD.<br><br>METHODS: The GSE207022 dataset, which consisted of 54 non-responders and 9 responders to UST in a CD cohort, was analyzed. Differentially expressed genes (DEGs) were identified and subjected to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. Least absolute shrinkage and selection operator (LASSO) regression was used to screen the most powerful hub genes. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the predictive performances of these genes. Single-sample Gene Set Enrichment Analysis (ssGSEA) was used to estimate the proportions of immune cell types. These significantly altered genes were subjected to cluster analysis into immune cell-related infiltration. To validate the reliability of the candidates, patients prescribed UST as a first-line biologic in a prospective cohort were included as an independent validation dataset.<br><br>RESULTS: A total of 99 DEGs were identified in the integrated dataset. GO and KEGG analyses revealed significant enrichment of immune response pathways in patients with CD. Thirteen genes (SOCS3, CD55, KDM5D, IGFBP5, LCN2, SLC15A1, XPNPEP2, HLA-DQA2, HMGCS2, DDX3Y, ITGB2, CDKN2B and HLA-DQA1), which were primarily associated with the response versus nonresponse patients, were identified and included in the LASSO analysis. These genes accurately predicted treatment response, with an area under the curve (AUC) of 0.938. T helper cell type 1 (Th1) cell polarization was comparatively strong in nonresponse individuals. Positive connections were observed between Th1 cells and the LCN2 and KDM5D genes. Furthermore, we employed an independent validation dataset and early experimental verification to validate the LCN2 and KDM5D genes as effective predictive markers.<br><br>CONCLUSIONS: Th1 cell polarization is an important cause of nonresponse to UST therapy in patients with CD. LCN2 and KDM5D can be used as predictive markers to effectively identify nonresponse patients.<br><br>TRIAL REGISTRATION: Trial registration number: NCT05542459; Date of registration: 2022-09-14; URL: https://www.<br><br>CLINICALTRIALS: gov .}, }
@article {pmid38924840, year = {2024}, author = {Yang, Y and Olah, P and Radai, Z and Maia, G and Salava, A and Salo, V and Barker, J and Lauerma, A and Andersson, B and Homey, B and Fyhrquist, N and Alenius, H}, title = {Exploratory multi-omics analysis reveals host-microbe interactions associated with disease severity in psoriatic skin.}, journal = {EBioMedicine}, volume = {105}, number = {}, pages = {105222}, pmid = {38924840}, issn = {2352-3964}, mesh = {Humans ; *Psoriasis/microbiology/genetics/metabolism ; *Metagenomics/methods ; *Skin/microbiology/metabolism/pathology ; Female ; Male ; Adult ; *Severity of Illness Index ; *Host Microbial Interactions/genetics ; *Microbiota ; Middle Aged ; Cross-Sectional Studies ; Metagenome ; Gene Expression Profiling ; Transcriptome ; Gene Regulatory Networks ; Host-Pathogen Interactions/genetics ; Computational Biology/methods ; Multiomics ; }, abstract = {BACKGROUND: Psoriasis (Pso) is a chronic inflammatory skin disease that poses both physical and psychological challenges. Dysbiosis of the skin microbiome has been implicated in Pso, yet a comprehensive multi-omics analysis of host-microbe interactions is still lacking. To bridge this gap, we conducted an exploratory study by adopting the integrated approach that combines whole metagenomic shotgun sequencing with skin transcriptomics.<br><br>METHODS: This was a cross-sectional study, adult patients with plaque-type Psoriasis (Pso) and healthy volunteers were included. Skin microbiota samples and biopsies were collected from both lesional and non-lesional skin areas on the lower back. Weighted Gene Correlation Network Analysis (WGCNA) was employed for co-expression network analysis, and cell deconvolution was conducted to estimate cell fractions. Taxonomic and functional features of the microbiome were identified using whole metagenomic shotgun sequencing. Association between host genes and microbes was analyzed using Spearman correlation.<br><br>FINDINGS: Host anti-viral responses and interferon-related networks were identified and correlated with the severity of psoriasis. The skin microbiome showed a greater prevalence of Corynebacterium simulans in the PASI severe-moderate groups, which correlated with interferon-induced host genes. Two distinct psoriatic clusters with varying disease severities were identified. Variations in the expression of cell apoptosis-associated antimicrobial peptides (AMPs) and microbial aerobic respiration I pathway may partly account for these differences in disease severity.<br><br>INTERPRETATION: Our multi-omics analysis revealed for the first time anti-viral responses and the presence of C.&#xa0;simulans associated with psoriasis severity. It also identified two psoriatic subtypes with distinct AMP and metabolic pathway expression. Our study provides new insights into understanding the host-microbe interaction in psoriasis and lays the groundwork for developing subtype-specific strategies for managing this chronic skin disease.<br><br>FUNDING: The research has received funding from the FP7 (MAARS-Grant 261366) and the Innovative Medicines Initiative 2 Joint Undertaking (JU) under grant agreement No 821511 (BIOMAP). The JU receives support from the European Union's Horizon 2020 research and innovation programme and EFPIA. This publication reflects only the author's view and the JU is not responsible for any use that may be made of the information it contains. GAM was supported by a scholarship provided by CAPES-PRINT, financed by the Coordena&#xe7;&#xe3;o de Aperfei&#xe7;oamento de Pessoal de N&#xed;vel Superior - CAPES (Brazilian Government Agency). The authors thank all patients who participated in our study.}, }
@article {pmid38923832, year = {2024}, author = {Del Giudice, G and Serra, A and Pavel, A and Torres Maia, M and Saarimäki, LA and Fratello, M and Federico, A and Alenius, H and Fadeel, B and Greco, D}, title = {A Network Toxicology Approach for Mechanistic Modelling of Nanomaterial Hazard and Adverse Outcomes.}, journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)}, volume = {11}, number = {32}, pages = {e2400389}, pmid = {38923832}, issn = {2198-3844}, support = {309329//EU FP7 project "NANOSOLUTIONS"/ ; 322761//Academy of Finland/ ; 101137742//EU project "INSIGHT"/ ; 101008099//CompSafeNano project/ ; 101043848/ERC_/European Research Council/International ; }, mesh = {*Nanostructures/toxicity ; *Adverse Outcome Pathways ; Humans ; Systems Biology/methods ; Animals ; Toxicology/methods ; }, abstract = {Hazard assessment is the first step in evaluating the potential adverse effects of chemicals. Traditionally, toxicological assessment has focused on the exposure, overlooking the impact of the exposed system on the observed toxicity. However, systems toxicology emphasizes how system properties significantly contribute to the observed response. Hence, systems theory states that interactions store more information than individual elements, leading to the adoption of network based models to represent complex systems in many fields of life sciences. Here, they develop a network-based approach to characterize toxicological responses in the context of a biological system, inferring biological system specific networks. They directly link molecular alterations to the adverse outcome pathway (AOP) framework, establishing direct connections between omics data and toxicologically relevant phenotypic events. They apply this framework to a dataset including 31 engineered nanomaterials with different physicochemical properties in two different in vitro and one in vivo models and demonstrate how the biological system is the driving force of the observed response. This work highlights the potential of network-based methods to significantly improve their understanding of toxicological mechanisms from a systems biology perspective and provides relevant considerations and future data-driven approaches for the hazard assessment of nanomaterials and other advanced materials.}, }
@article {pmid38912690, year = {2024}, author = {Byndloss, M and Devkota, S and Duca, F and Niess, JH and Nieuwdorp, M and Orho-Melander, M and Sanz, Y and Tremaroli, V and Zhao, L}, title = {The Gut Microbiota and Diabetes: Research, Translation, and Clinical Applications-2023 Diabetes, Diabetes Care, and Diabetologia Expert Forum.}, journal = {Diabetes}, volume = {73}, number = {9}, pages = {1391-1410}, pmid = {38912690}, issn = {1939-327X}, support = {PID2020-119536RB-I00//Spanish Ministry of Science, Innovation and Universities MICIU/AEI/ ; 2020 (09150182010020)//ZONMW-VICI/ ; //Novo Nordisk Foundation/ ; DP1 DK130687/DK/NIDDK NIH HHS/United States ; CEX2021-001189-S/10.13039/501100011033//Severo Ochoa Center of Excellence/ ; 1DP1 DK130687/DK/NIDDK NIH HHS/United States ; 310030_219210//Swiss National Science Foundation (SNSF)/ ; R01 DK123446/DK/NIDDK NIH HHS/United States ; 875534//European Union&#xe2;&#x20ac;&#x2122;s Innovative Medicine Initiative/ ; R01 DK131104/DK/NIDDK NIH HHS/United States ; 2020 (2020.10.002)//DFN-DON/ ; }, mesh = {*Gastrointestinal Microbiome/physiology ; Humans ; *Diabetes Mellitus, Type 2/microbiology/metabolism/therapy ; Translational Research, Biomedical ; }, abstract = {This article summarizes the state of the science on the role of the gut microbiota (GM) in diabetes from a recent international expert forum organized by Diabetes, Diabetes Care, and Diabetologia, which was held at the European Association for the Study of Diabetes 2023 Annual Meeting in Hamburg, Germany. Forum participants included clinicians and basic scientists who are leading investigators in the field of the intestinal microbiome and metabolism. Their conclusions were as follows: 1) the GM may be involved in the pathophysiology of type 2 diabetes, as microbially produced metabolites associate both positively and negatively with the disease, and mechanistic links of GM functions (e.g., genes for butyrate production) with glucose metabolism have recently emerged through the use of Mendelian randomization in humans; 2) the highly individualized nature of the GM poses a major research obstacle, and large cohorts and a deep-sequencing metagenomic approach are required for robust assessments of associations and causation; 3) because single-time point sampling misses intraindividual GM dynamics, future studies with repeated measures within individuals are needed; and 4) much future research will be required to determine the applicability of this expanding knowledge to diabetes diagnosis and treatment, and novel technologies and improved computational tools will be important to achieve this goal.}, }
@article {pmid38910152, year = {2024}, author = {Byndloss, M and Devkota, S and Duca, F and Niess, JH and Nieuwdorp, M and Orho-Melander, M and Sanz, Y and Tremaroli, V and Zhao, L}, title = {The gut microbiota and diabetes: research, translation, and clinical applications - 2023 Diabetes, Diabetes Care, and Diabetologia Expert Forum.}, journal = {Diabetologia}, volume = {67}, number = {9}, pages = {1760-1782}, pmid = {38910152}, issn = {1432-0428}, support = {R01 DK131104/DK/NIDDK NIH HHS/United States ; }, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Diabetes Mellitus, Type 2/microbiology/metabolism ; Translational Research, Biomedical ; }, abstract = {This article summarises the state of the science on the role of the gut microbiota (GM) in diabetes from a recent international expert forum organised by Diabetes, Diabetes Care, and Diabetologia, which was held at the European Association for the Study of Diabetes 2023 Annual Meeting in Hamburg, Germany. Forum participants included clinicians and basic scientists who are leading investigators in the field of the intestinal microbiome and metabolism. Their conclusions were as follows: (1) the GM may be involved in the pathophysiology of type 2 diabetes, as microbially produced metabolites associate both positively and negatively with the disease, and mechanistic links of GM functions (e.g. genes for butyrate production) with glucose metabolism have recently emerged through the use of Mendelian randomisation in humans; (2) the highly individualised nature of the GM poses a major research obstacle, and large cohorts and a deep-sequencing metagenomic approach are required for robust assessments of associations and causation; (3) because single time point sampling misses intraindividual GM dynamics, future studies with repeated measures within individuals are needed; and (4) much future research will be required to determine the applicability of this expanding knowledge to diabetes diagnosis and treatment, and novel technologies and improved computational tools will be important to achieve this goal.}, }
@article {pmid38909617, year = {2024}, author = {Kullberg, RFJ and Wikki, I and Haak, BW and Kauko, A and Galenkamp, H and Peters-Sengers, H and Butler, JM and Havulinna, AS and Palmu, J and McDonald, D and Benchraka, C and Abdel-Aziz, MI and Prins, M and Maitland van der Zee, AH and van den Born, BJ and Jousilahti, P and de Vos, WM and Salomaa, V and Knight, R and Lahti, L and Nieuwdorp, M and Niiranen, T and Wiersinga, WJ}, title = {Association between butyrate-producing gut bacteria and the risk of infectious disease hospitalisation: results from two observational, population-based microbiome studies.}, journal = {The Lancet. Microbe}, volume = {5}, number = {9}, pages = {100864}, doi = {10.1016/S2666-5247(24)00079-X}, pmid = {38909617}, issn = {2666-5247}, mesh = {Humans ; Middle Aged ; Adult ; *Hospitalization/statistics &amp; numerical data ; Male ; Female ; *Gastrointestinal Microbiome/physiology ; Aged ; Finland/epidemiology ; *Butyrates/metabolism ; *RNA, Ribosomal, 16S/genetics/analysis ; Netherlands/epidemiology ; Young Adult ; *Bacteria/genetics/classification/isolation &amp; purification ; Feces/microbiology ; Adolescent ; Communicable Diseases/microbiology/epidemiology ; Cohort Studies ; Risk Factors ; }, abstract = {BACKGROUND: Microbiota alterations are common in patients hospitalised for severe infections, and preclinical models have shown that anaerobic butyrate-producing gut bacteria protect against systemic infections. However, the relationship between microbiota disruptions and increased susceptibility to severe infections in humans remains unclear. We investigated the relationship between gut microbiota and the risk of future infection-related hospitalisation in two large population-based cohorts.<br><br>METHODS: In this observational microbiome study, gut microbiota were characterised using 16S rRNA gene sequencing in independent population-based cohorts from the Netherlands (HELIUS study; derivation cohort) and Finland (FINRISK 2002 study; validation cohort). HELIUS was conducted in Amsterdam, Netherlands, and included adults (aged 18-70 years at inclusion) who were randomly sampled from the municipality register of Amsterdam. FINRISK 2002 was conducted in six regions in Finland and is a population survey that included a random sample of adults (aged 25-74 years). In both cohorts, participants completed questionnaires, underwent a physical examination, and provided a faecal sample at inclusion (Jan 3, 2013, to Nov 27, 2015, for HELIUS participants and Jan 21 to April 19, 2002, for FINRISK participants. For inclusion in our study, a faecal sample needed to be provided and successfully sequenced, and national registry data needed to be available. Primary predictor variables were microbiota composition, diversity, and relative abundance of butyrate-producing bacteria. Our primary outcome was hospitalisation or mortality due to any infectious disease during 5-7-year follow-up after faecal sample collection, based on national registry data. We examined associations between microbiota and infection risk using microbial ecology and Cox proportional hazards.<br><br>FINDINGS: We profiled gut microbiota from 10&#x2009;699 participants (4248 [39&#xb7;7%] from the derivation cohort and 6451&#xa0;[60&#xb7;3%] from the validation cohort). 602 (5&#xb7;6%) participants (152 [3&#xb7;6%] from the derivation cohort; 450 [7&#xb7;0%] from the validation cohort) were hospitalised or died due to infections during follow-up. Gut microbiota composition of these participants differed from those without hospitalisation for infections (derivation p=0&#xb7;041; validation p=0&#xb7;0002). Specifically, higher relative abundance of butyrate-producing bacteria was associated with a reduced risk of hospitalisation for infections (derivation cohort cause-specific hazard ratio 0&#xb7;75 [95% CI 0&#xb7;60-0&#xb7;94] per 10% increase in butyrate producers, p=0&#xb7;013; validation cohort 0&#xb7;86 [0&#xb7;77-0&#xb7;96] per 10% increase, p=0&#xb7;0077). These associations remained unchanged following adjustment for demographics, lifestyle, antibiotic exposure, and comorbidities.<br><br>INTERPRETATION: Gut microbiota composition, specifically colonisation with butyrate-producing bacteria, was associated with protection against hospitalisation for infectious diseases in the general population across two independent European cohorts. Further studies should investigate whether modulation of the microbiome can reduce the risk of severe infections.<br><br>FUNDING: Amsterdam UMC, Porticus, National Institutes of Health, Netherlands Organisation for Health Research and Development (ZonMw), and Leducq Foundation.}, }
@article {pmid38904934, year = {2024}, author = {Peer, A and Samuelson, DR}, title = {The Role of the Microbiome in Allergy, Asthma, and Occupational Lung Disease.}, journal = {Current allergy and asthma reports}, volume = {24}, number = {8}, pages = {415-423}, pmid = {38904934}, issn = {1534-6315}, support = {P50 AA030407/AA/NIAAA NIH HHS/United States ; R01 DK131990/DK/NIDDK NIH HHS/United States ; R01-DK131990-01/DK/NIDDK NIH HHS/United States ; P50-AA030407/AA/NIAAA NIH HHS/United States ; }, mesh = {Humans ; *Microbiota/immunology ; *Asthma/immunology/microbiology ; *Hypersensitivity/immunology/microbiology ; *Occupational Diseases/microbiology/immunology ; Occupational Exposure/adverse effects ; Lung Diseases/microbiology/immunology ; }, abstract = {PURPOSE OF REVIEW: The human commensal microbiota is now widely accepted as a key regulator of human health and disease. The composition of the mucosal associated microbiota has been shown to play a critical role in the lung health. The role of the mucosal microbiota in the development and severity of allergy, asthma, and occupational lung disease is only beginning to take shape. However, advances in our understanding of these links have tremendous potential to led to new clinical interventions to reduce allergy, asthma, and occupational lung disease morbidity.<br><br>RECENT FINDINGS: We review recent work describing the relationship and role of the commensal microbiota in the development of allergy, asthma, and occupational lung disease. Our review primarily focuses on occupational exposures and the effects of the microbiome, both in composition and function. Data generated from these studies may lead to the development of interventions targeted at establishing and maintaining a healthy microbiota. We also highlight the role of environmental exposures and the effects on the commensal microbial community and their potential association with occupational lung disease. This review explores the current research describing the role of the human microbiome in the regulation of pulmonary health and disease, with a specific focus on the role of the mucosal microbiota in the development of allergy, asthma, and occupational lung disease.}, }
@article {pmid38899893, year = {2024}, author = {He, J and Ma, M and Xu, Z and Guo, J and Chen, H and Yang, X and Chen, P and Liu, G}, title = {Association between semen microbiome disorder and sperm DNA damage.}, journal = {Microbiology spectrum}, volume = {12}, number = {8}, pages = {e0075924}, pmid = {38899893}, issn = {2165-0497}, support = {81971759//MOST | National Natural Science Foundation of China (NSFC)/ ; 82171604//MOST | National Natural Science Foundation of China (NSFC)/ ; }, mesh = {Male ; Humans ; *Microbiota/genetics ; *Spermatozoa/microbiology/metabolism ; *DNA Fragmentation ; *DNA Damage ; Adult ; *Semen/microbiology ; *RNA, Ribosomal, 16S/genetics ; *Infertility, Male/microbiology/metabolism ; Lactobacillus/genetics/metabolism/isolation &amp; purification ; Bacteria/genetics/classification/isolation &amp; purification/metabolism ; Semen Analysis ; }, abstract = {DNA fragmentation index (DFI), a new biomarker to diagnose male infertility, is closely associated with poor reproductive outcomes. Previous research reported that seminal microbiome correlated with sperm DNA integrity, suggesting that the microbiome may be one of the causes of DNA damage in sperm. However, it has not been elucidated how the microbiota exerts their effects. Here, we used a combination of 16S rRNA sequencing and untargeted metabolomics techniques to investigate the role of microbiota in high sperm DNA fragmentation index (HDFI). We report that increased specific microbial profiles contribute to high sperm DNA fragmentation, thus implicating the seminal microbiome as a new therapeutic target for HDFI patients. Additionally, we found that the amount of Lactobacillus species was altered: Lactobacillus iners was enriched in HDFI patients, shedding light on the potential influence of L. iners on male reproductive health. Finally, we also identified enrichment of the acetyl-CoA fermentation to butanoate II and purine nucleobase degradation I in the high sperm DNA fragmentation samples, suggesting that butanoate may be the target metabolite of sperm DNA damage. These findings provide valuable insights into the complex interplay between microbiota and sperm quality in HDFI patients, laying the foundation for further research and potential clinical interventions.IMPORTANCEThe DNA fragmentation index (DFI) is a measure of sperm DNA fragmentation. Because high sperm DNA fragmentation index (HDFI) has been strongly associated with adverse reproductive outcomes, this has been linked to the seminal microbiome. Because the number of current treatments for HDFI is limited and most of them have no clear efficacy, it is critical to understand how semen microbiome exerts their effects on sperm DNA. Here, we evaluated the semen microbiome and its metabolites in patients with high and low sperm DNA fragmentation. We found that increased specific microbial profiles contribute to high sperm DNA fragmentation. In particular, Lactobacillus iners was uniquely correlated with high sperm DNA fragmentation. Additionally, butanoate may be the target metabolite produced by the microbiome to damage sperm DNA. Our findings support the interaction between semen microbiome and sperm DNA damage and suggest that seminal microbiome should be a new therapeutic target for HDFI patients.}, }
@article {pmid38898695, year = {2024}, author = {Wisgrill, L and Martens, A and Kasbauer, R and Eigenschink, M and Pummer, L and Redlberger-Fritz, M and Végvári, &#xc1; and Warth, B and Berger, A and Fyhrquist, N and Alenius, H}, title = {Network analysis reveals age- and virus-specific circuits in nasal epithelial cells of extremely premature infants.}, journal = {Allergy}, volume = {79}, number = {11}, pages = {3062-3081}, doi = {10.1111/all.16196}, pmid = {38898695}, issn = {1398-9995}, support = {[10.47379/LS20025]//Vienna Science and Technology Fund/ ; 2020-02090//Vetenskapsr&#xe5;det/ ; }, mesh = {Humans ; *Nasal Mucosa/virology/immunology/cytology ; *Infant, Extremely Premature/immunology ; Infant, Newborn ; *Immunity, Innate ; *Epithelial Cells/immunology/virology ; Age Factors ; Influenza A virus/immunology ; Respiratory Syncytial Virus Infections/immunology ; Adult ; }, abstract = {BACKGROUND AND OBJECTIVES: Viral respiratory infections significantly affect young children, particularly extremely premature infants, resulting in high hospitalization rates and increased health-care burdens. Nasal epithelial cells, the primary defense against respiratory infections, are vital for understanding nasal immune responses and serve as a promising target for uncovering underlying molecular and cellular mechanisms.<br><br>METHODS: Using a trans-well pseudostratified nasal epithelial cell system, we examined age-dependent developmental differences and antiviral responses to influenza A and respiratory syncytial virus through systems biology approaches.<br><br>RESULTS: Our studies revealed differences in innate-receptor repertoires, distinct developmental pathways, and differentially connected antiviral network circuits between neonatal and adult nasal epithelial cells. Consensus network analysis identified unique and shared cellular-viral networks, emphasizing highly relevant virus-specific pathways, independent of viral replication kinetics.<br><br>CONCLUSION: This research highlights the importance of nasal epithelial cells in innate antiviral immune responses and offers crucial insights that allow for a deeper understanding of age-related differences in nasal epithelial cell immunity following respiratory virus infections.}, }
@article {pmid38898021, year = {2024}, author = {Zhu, B and Edwards, DJ and Spaine, KM and Edupuganti, L and Matveyev, A and Serrano, MG and Buck, GA}, title = {The association of maternal factors with the neonatal microbiota and health.}, journal = {Nature communications}, volume = {15}, number = {1}, pages = {5260}, pmid = {38898021}, issn = {2041-1723}, support = {R01HD092415//Foundation for the National Institutes of Health (Foundation for the National Institutes of Health, Inc.)/ ; UH3AI083263//Foundation for the National Institutes of Health (Foundation for the National Institutes of Health, Inc.)/ ; UH3 AI083263/AI/NIAID NIH HHS/United States ; R01 HD092415/HD/NICHD NIH HHS/United States ; U54 HD080784/HD/NICHD NIH HHS/United States ; U54HD080784//Foundation for the National Institutes of Health (Foundation for the National Institutes of Health, Inc.)/ ; }, mesh = {Humans ; Female ; Infant, Newborn ; Pregnancy ; *Feces/microbiology ; *Microbiota ; Adult ; Cesarean Section ; Premature Birth/microbiology ; Gastrointestinal Microbiome/physiology ; Mouth/microbiology ; Rectum/microbiology ; Male ; }, abstract = {The human microbiome plays a crucial role in human health. However, the influence of maternal factors on the neonatal microbiota remains obscure. Herein, our observations suggest that the neonatal microbiotas, particularly the buccal microbiota, change rapidly within 24-48 h of birth but begin to stabilize by 48-72 h after parturition. Network analysis clustered over 200 maternal factors into thirteen distinct groups, and most associated factors were in the same group. Multiple maternal factor groups were associated with the neonatal buccal, rectal, and stool microbiotas. Particularly, a higher maternal inflammatory state and a lower maternal socioeconomic position were associated with a higher alpha diversity of the neonatal buccal microbiota and beta diversity of the neonatal stool microbiota was influenced by maternal diet and cesarean section by 24-72 h postpartum. The risk of admission of a neonate to the newborn intensive care unit was associated with preterm birth as well as higher cytokine levels and probably higher alpha diversity of the maternal buccal microbiota.}, }
@article {pmid38892281, year = {2024}, author = {Bose, D and Saha, P and Roy, S and Trivedi, A and More, M and Klimas, N and Tuteja, A and Chatterjee, S}, title = {A Double-Humanized Mouse Model for Studying Host Gut Microbiome-Immune Interactions in Gulf War Illness.}, journal = {International journal of molecular sciences}, volume = {25}, number = {11}, pages = {}, pmid = {38892281}, issn = {1422-0067}, support = {I01 CX001923/CX/CSRD VA/United States ; I01CX0001923//United States Department of Veterans Affairs/ ; }, mesh = {Animals ; *Gastrointestinal Microbiome ; *Persian Gulf Syndrome/immunology/microbiology ; Humans ; Mice ; *Disease Models, Animal ; *Cytokines/metabolism ; Fecal Microbiota Transplantation ; }, abstract = {Unraveling the multisymptomatic Gulf War Illness (GWI) pathology and finding an effective cure have eluded researchers for decades. The chronic symptom persistence and limitations for studying the etiologies in mouse models that differ significantly from those in humans pose challenges for drug discovery and finding effective therapeutic regimens. The GWI exposome differs significantly in the study cohorts, and the above makes it difficult to recreate a model closely resembling the GWI symptom pathology. We have used a double engraftment strategy for reconstituting a human immune system coupled with human microbiome transfer to create a humanized-mouse model for GWI. Using whole-genome shotgun sequencing and blood immune cytokine enzyme linked immunosorbent assay (ELISA), we show that our double humanized mice treated with Gulf War (GW) chemicals show significantly altered gut microbiomes, similar to those reported in a Veteran cohort of GWI. The results also showed similar cytokine profiles, such as increased levels of IL-1β, IL-6, and TNF R-1, in the double humanized model, as found previously in a human cohort. Further, a novel GWI Veteran fecal microbiota transfer was used to create a second alternative model that closely resembled the microbiome and immune-system-associated pathology of a GWI Veteran. A GWI Veteran microbiota transplant in humanized mice showed a human microbiome reconstitution and a systemic inflammatory pathology, as reflected by increases in interleukins 1β, 6, 8 (IL-1β, IL-6, IL-8), tumor necrosis factor receptor 1 (TNF R-1), and endotoxemia. In conclusion, though preliminary, we report a novel in vivo model with a human microbiome reconstitution and an engrafted human immune phenotype that may help to better understand gut-immune interactions in GWI.}, }
@article {pmid38890378, year = {2024}, author = {Khawaja, T and Mäklin, T and Kallonen, T and Gladstone, RA and Pöntinen, AK and Mero, S and Thorpe, HA and Samuelsen, &#xd8; and Parkhill, J and Izhar, M and Akhtar, MW and Corander, J and Kantele, A}, title = {Deep sequencing of Escherichia coli exposes colonisation diversity and impact of antibiotics in Punjab, Pakistan.}, journal = {Nature communications}, volume = {15}, number = {1}, pages = {5196}, pmid = {38890378}, issn = {2041-1723}, support = {/WT_/Wellcome Trust/United Kingdom ; AMRIWA//Academy of Finland (Suomen Akatemia)/ ; 206194/WT_/Wellcome Trust/United Kingdom ; EuroHPC//Academy of Finland (Suomen Akatemia)/ ; }, mesh = {Pakistan/epidemiology ; Humans ; *Escherichia coli/genetics/drug effects/isolation &amp; purification ; *Anti-Bacterial Agents/pharmacology ; *Escherichia coli Infections/epidemiology/microbiology/drug therapy ; *Drug Resistance, Multiple, Bacterial/genetics ; *High-Throughput Nucleotide Sequencing ; Feces/microbiology ; Female ; Male ; Genome, Bacterial/genetics ; Adult ; Genetic Variation ; Middle Aged ; Young Adult ; Phylogeny ; Adolescent ; Child ; }, abstract = {Multi-drug resistant (MDR) E. coli constitute a major public health burden globally, reaching the highest prevalence in the global south yet frequently flowing with travellers to other regions. However, our comprehension of the entire genetic diversity of E. coli colonising local populations remains limited. We quantified this diversity, its associated antimicrobial resistance (AMR), and assessed the impact of antibiotic use by recruiting 494 outpatients and 423 community dwellers in the Punjab province, Pakistan. Rectal swab and stool samples were cultured on CLED agar and DNA extracted from plate sweeps was sequenced en masse to capture both the genetic and AMR diversity of E. coli. We assembled 5,247 E. coli genomes from 1,411 samples, displaying marked genetic diversity in gut colonisation. Compared with high income countries, the Punjabi population generally showed a markedly different distribution of genetic lineages and AMR determinants, while use of antibiotics elevated the prevalence of well-known globally circulating MDR clinical strains. These findings implicate that longitudinal multi-regional genomics-based surveillance of both colonisation and infections is a prerequisite for developing mechanistic understanding of the interplay between ecology and evolution in the maintenance and dissemination of (MDR) E. coli.}, }
@article {pmid38890150, year = {2024}, author = {Fu, C and Zhang, Y and Liang, L and Lin, H and Shan, K and Liu, F and Feng, N}, title = {The microbiota in patients with interstitial cystitis/bladder pain syndrome: a systematic review.}, journal = {BJU international}, volume = {134}, number = {6}, pages = {869-880}, doi = {10.1111/bju.16439}, pmid = {38890150}, issn = {1464-410X}, support = {THRCJH20200104//Wuxi Taihu Lake Talent Plan, Leading Talents in Medical and Health Profession Project/ ; }, mesh = {*Cystitis, Interstitial/microbiology ; Humans ; *Microbiota ; Female ; Gastrointestinal Microbiome ; Vagina/microbiology ; }, abstract = {OBJECTIVE: To comprehensively review and critically assess the literature on microbiota differences between patients with interstitial cystitis (IC)/bladder pain syndrome (BPS) and normal controls and to provide clinical practice guidelines.<br><br>MATERIALS AND METHODS: In this systematic review, we evaluated previous research on microbiota disparities between IC/BPS and normal controls, as well as distinctions among IC/BPS subgroups. A comprehensive literature search was conducted across PubMed/MEDLINE, EMBASE, Web of Science, and the Cochrane Central Register of Controlled Trials. Relevant studies were shortlisted based on predetermined inclusion and exclusion criteria, followed by quality assessment. The primary focus was identifying specific taxonomic variations among these cohorts.<br><br>RESULTS: A total of 12 studies met the selection criteria. Discrepancies were adjudicated by a third reviewer. The Newcastle-Ottawa Scale was used to assess study quality. Predominantly, the studies focused on disparities in urine microbiota between IC/BPS patients and normal controls, with one study examining gut microbiota differences between the groups, and two studies exploring vaginal microbiota distinctions. Unfortunately, analyses of discrepancies in other microbiota were limited. Our findings revealed evidence of distinct bacterial abundance variations, particularly involving Lactobacillus, alongside variations in specific metabolites among IC/BPS patients compared to controls.<br><br>CONCLUSIONS: Currently, there is evidence suggesting significant variations in the diversity and species composition of the urinary microbiota between individuals diagnosed with IC/BPS and control groups. In the foreseeable future, urologists should consider urine microbiota dysbiosis as a potential aetiology for IC, with potential clinical implications for diagnosis and treatment.}, }
@article {pmid38884446, year = {2024}, author = {Moussa, AY}, title = {Streptomyces Endophytes in Edible Plants: New Insights into their Chemistry and Health Benefits.}, journal = {Chemistry &amp; biodiversity}, volume = {21}, number = {10}, pages = {e202400888}, doi = {10.1002/cbdv.202400888}, pmid = {38884446}, issn = {1612-1880}, mesh = {*Streptomyces/chemistry/metabolism/isolation &amp; purification ; *Endophytes/chemistry/metabolism ; Humans ; *Plants, Edible/chemistry/microbiology ; Anti-Bacterial Agents/pharmacology/chemistry/isolation &amp; purification ; }, abstract = {Streptomyces is the largest source of microbial antibiotics with about 50 % of marketed antimicrobial drugs originating from this genus. Endophytic streptomyces are the link between medicinal plants and the microbial world. Endophytic Streptomyces in edible plants were not targeted before despite their uniqueness and importance. In this review, we analyzed the chemical diversity of more than 150 compounds belonging to endophytic Streptomyces chemical classes such as alkaloids, polyketides, peptides, macrolides and terpenes and their biological activities. This analysis showed a dominant antimicrobial effect for most of the isolated compounds and highlighted an underestimated diversity to be studied or repurposed for other biological activities. Return to edible plants use and conducting toxicity studies to rationalize their nutraceutical potential based on their beneficial endophytes is urged. Although there are many studies for non-vertebrates, the nutraceutical potential of these plants is expected to improve the gut microbiota since they are enriched with bioactive compounds from streptomyces species. This is the first review to discuss edible plants associated streptomyces, and we prospect that many studies will follow to unravel the mysterious health benefits of streptomyces in the human microbiome and encourage the revival of a correct lifestyle for the sake of a healthier microbiome.}, }
@article {pmid38882496, year = {2024}, author = {Zhang, Z and Zhang, HL and Yang, DH and Hao, Q and Yang, HW and Meng, DL and Meindert de Vos, W and Guan, LL and Liu, SB and Teame, T and Gao, CC and Ran, C and Yang, YL and Yao, YY and Ding, QW and Zhou, ZG}, title = {Lactobacillus rhamnosus GG triggers intestinal epithelium injury in zebrafish revealing host dependent beneficial effects.}, journal = {iMeta}, volume = {3}, number = {2}, pages = {e181}, pmid = {38882496}, issn = {2770-596X}, abstract = {Lactobacillus rhamnosus GG (LGG), the well-characterized human-derived probiotic strain, possesses excellent properties in the maintenance of intestinal homeostasis, immunoregulation and defense against gastrointestinal pathogens in mammals. Here, we demonstrate that the SpaC pilin of LGG causes intestinal epithelium injury by inducing cell pyroptosis and gut microbial dysbiosis in zebrafish. Dietary SpaC activates Caspase-3-GSDMEa pathways in the intestinal epithelium, promotes intestinal pyroptosis and increases lipopolysaccharide (LPS)-producing gut microbes in zebrafish. The increased LPS subsequently activates Gaspy2-GSDMEb pyroptosis pathway. Further analysis reveals the Caspase-3-GSDMEa pyroptosis is initiated by the species-specific recognition of SpaC by TLR4ba, which accounts for the species-specificity of the SpaC-inducing intestinal pyroptosis in zebrafish. The observed pyroptosis-driven gut injury and microbial dysbiosis by LGG in zebrafish suggest that host-specific beneficial/harmful mechanisms are critical safety issues when applying probiotics derived from other host species and need more attention.}, }
@article {pmid38882486, year = {2024}, author = {Wu, D and Guan, YX and Li, CH and Zheng, Q and Yin, ZJ and Wang, H and Liu, NN}, title = {"Nutrient-fungi-host" tripartite interaction in cancer progression.}, journal = {iMeta}, volume = {3}, number = {2}, pages = {e170}, pmid = {38882486}, issn = {2770-596X}, abstract = {The human microbiome exhibits a profound connection with the cancer development, progression, and therapeutic response, with particular emphasis on its components of the mycobiome, which are still in the early stages of research. In this review, we comprehensively summarize cancer-related symbiotic and pathogenic fungal genera. The intricate mechanisms through which fungi impact cancer as an integral member of both gut and tissue-resident microbiomes are further discussed. In addition, we shed light on the pivotal physiological roles of various nutrients, including cholesterol, carbohydrates, proteins and minerals, in facilitating the growth, reproduction, and invasive pathogenesis of the fungi. While our exploration of the interplay between nutrients and cancer, mediated by the mycobiome, is ongoing, the current findings have yet to yield conclusive results. Thus, delving into the relationship between nutrients and fungal pathogenesis in cancer development and progression would provide valuable insights into anticancer therapy and foster precision nutrition and individualized treatments that target fungi from bench to bedside.}, }
@article {pmid38878076, year = {2024}, author = {Jawanda, IK and Soni, T and Kumari, S and Prabha, V}, title = {The evolving facets of vaginal microbiota transplantation: reinvigorating the unexplored frontier amid complex challenges.}, journal = {Archives of microbiology}, volume = {206}, number = {7}, pages = {306}, pmid = {38878076}, issn = {1432-072X}, mesh = {Animals ; Female ; Humans ; Anti-Bacterial Agents/therapeutic use ; *Dysbiosis/microbiology/therapy ; Lactobacillus ; *Microbiota ; *Probiotics/administration &amp; dosage ; *Vagina/microbiology ; }, abstract = {In an age of cutting-edge sequencing methods and worldwide endeavors such as The Human Microbiome Project and MetaHIT, the human microbiome stands as a complex and diverse community of microorganisms. A central theme in current scientific inquiry revolves around reinstating a balanced microbial composition, referred to as "eubiosis," as a targeted approach for treating vast array of diseases. Vaginal Microbiota Transplantation (VMT), inspired by the success of fecal microbiota transplantation, emerges as an innovative therapy addressing vaginal dysbacteriosis by transferring the complete microbiota from a healthy donor. Antibiotics, while effective, pose challenges with adverse effects, high recurrence rates, and potential harm to beneficial Lactobacillus strains. Continued antibiotic usage also sparks worries regarding the development of resistant strains. Probiotics, though showing promise, exhibit inconsistency in treating multifactorial diseases, and concerns linger about their suitability for diverse genetic backgrounds. Given the recurrent challenges associated with antibiotic and probiotic treatments, VMT emerges as an imperative alternative, offering a unique and promising avenue for efficiently and reliably managing vaginal dysbiosis among a majority of women. This review critically evaluates findings from both animal and human studies, offering nuanced insights into the efficacy and challenges of VMT. An extensive analysis of clinical trials, provides a current overview of ongoing and completed trials, shedding light on the evolving clinical landscape and therapeutic potential of VMT. Delving into the origins, mechanisms, and optimized protocols of VMT, the review underscores the imperative for sustained research efforts to advance this groundbreaking gynecological therapy.}, }
@article {pmid38874821, year = {2024}, author = {Wu, K and Chen, J and Lin, J and Zhu, E and Xu, X and Yan, X and Ju, L and Huang, M and Zhang, Y}, title = {The role of ferroptosis in DM-induced liver injury.}, journal = {Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine}, volume = {37}, number = {5}, pages = {1191-1200}, pmid = {38874821}, issn = {1572-8773}, mesh = {Animals ; *Ferroptosis ; Male ; Rats ; *Receptors, Transferrin/metabolism ; *Phospholipid Hydroperoxide Glutathione Peroxidase/metabolism ; Diabetes Mellitus, Experimental/metabolism/pathology/chemically induced ; Rats, Sprague-Dawley ; Liver/pathology/metabolism ; Streptozocin ; Superoxide Dismutase/metabolism ; Glutathione/metabolism ; Cation Transport Proteins/metabolism/genetics ; Malondialdehyde/metabolism ; Iron/metabolism ; Ferroportin ; }, abstract = {The liver damage caused by Diabetes Mellitus (DM) has attracted increasing attention in recent years. Liver injury in DM can be caused by ferroptosis, a form of cell death caused by iron overload. However, the role of iron transporters in this context is still not clear. Herein, we attempted to shed light on the pathophysiological mechanism of ferroptosis. DM was induced in 8-week-old male rats by streptozotocin (STZ) before assessment of the degree of liver injury. Together with histopathological changes, variations in glutathione peroxidase 4 (GPX4), glutathione (GSH), superoxide dismutase (SOD), transferrin receptor 1 (TFR1), ferritin heavy chain (FTH), ferritin light chain (FTL), ferroportin and Prussian blue staining, were monitored in rat livers before and after treatment with Fer-1. In the liver of STZ-treated rats, GSH and SOD levels decreased, whereas those of malondialdehyde (MDA) increased. Expression of TFR1, FTH and FTL increased whereas that of glutathione peroxidase 4 (GPX4) and ferroportin did not change significantly. Prussian blue staining showed that iron levels increased. Histopathology showed liver fibrosis and decreased glycogen content. Fer-1 treatment reduced iron and MDA levels but GSH and SOD levels were unchanged. Expression of FTH and FTL was reduced whereas that of ferroportin showed a mild decrease. Fer-1 treatment alleviated liver fibrosis, increased glycogen content and mildly improved liver function. Our study demonstrates that ferroptosis is involved in DM-induced liver injury. Regulating the levels of iron transporters may become a new therapeutic strategy in ferroptosis-induced liver injury.}, }
@article {pmid38873568, year = {2024}, author = {Shang, Z and Pai, L and Patil, S}, title = {Unveiling the dynamics of gut microbial interactions: a review of dietary impact and precision nutrition in gastrointestinal health.}, journal = {Frontiers in nutrition}, volume = {11}, number = {}, pages = {1395664}, pmid = {38873568}, issn = {2296-861X}, abstract = {The human microbiome, a dynamic ecosystem within the gastrointestinal tract, plays a pivotal role in shaping overall health. This review delves into six interconnected sections, unraveling the intricate relationship between diet, gut microbiota, and their profound impact on human health. The dance of nutrients in the gut orchestrates a complex symphony, influencing digestive processes and susceptibility to gastrointestinal disorders. Emphasizing the bidirectional communication between the gut and the brain, the Brain-Gut Axis section highlights the crucial role of dietary choices in physical, mental, and emotional well-being. Autoimmune diseases, particularly those manifesting in the gastrointestinal tract, reveal the delicate balance disrupted by gut microbiome imbalances. Strategies for reconciling gut microbes through diets, precision nutrition, and clinical indications showcase promising avenues for managing gastrointestinal distress and revolutionizing healthcare. From the Low-FODMAP diet to neuro-gut interventions, these strategies provide a holistic understanding of the gut's dynamic world. Precision nutrition, as a groundbreaking discipline, holds transformative potential by tailoring dietary recommendations to individual gut microbiota compositions, reshaping the landscape of gastrointestinal health. Recent advancements in clinical indications, including exact probiotics, fecal microbiota transplantation, and neuro-gut interventions, signify a new era where the gut microbiome actively participates in therapeutic strategies. As the microbiome takes center stage in healthcare, a paradigm shift toward personalized and effective treatments for gastrointestinal disorders emerges, reflecting the symbiotic relationship between the human body and its microbial companions.}, }
@article {pmid38873138, year = {2024}, author = {Chi, J and Ye, J and Zhou, Y}, title = {A GLM-based zero-inflated generalized Poisson factor model for analyzing microbiome data.}, journal = {Frontiers in microbiology}, volume = {15}, number = {}, pages = {1394204}, pmid = {38873138}, issn = {1664-302X}, abstract = {MOTIVATION: High-throughput sequencing technology facilitates the quantitative analysis of microbial communities, improving the capacity to investigate the associations between the human microbiome and diseases. Our primary motivating application is to explore the association between gut microbes and obesity. The complex characteristics of microbiome data, including high dimensionality, zero inflation, and over-dispersion, pose new statistical challenges for downstream analysis.<br><br>RESULTS: We propose a GLM-based zero-inflated generalized Poisson factor analysis (GZIGPFA) model to analyze microbiome data with complex characteristics. The GZIGPFA model is based on a zero-inflated generalized Poisson (ZIGP) distribution for modeling microbiome count data. A link function between the generalized Poisson rate and the probability of excess zeros is established within the generalized linear model (GLM) framework. The latent parameters of the GZIGPFA model constitute a low-rank matrix comprising a low-dimensional score matrix and a loading matrix. An alternating maximum likelihood algorithm is employed to estimate the unknown parameters, and cross-validation is utilized to determine the rank of the model in this study. The proposed GZIGPFA model demonstrates superior performance and advantages through comprehensive simulation studies and real data applications.}, }
@article {pmid38868076, year = {2024}, author = {Takallu, S and Aiyelabegan, HT and Zomorodi, AR and Alexandrovna, KV and Aflakian, F and Asvar, Z and Moradi, F and Behbahani, MR and Mirzaei, E and Sarhadi, F and Vakili-Ghartavol, R}, title = {Nanotechnology improves the detection of bacteria: Recent advances and future perspectives.}, journal = {Heliyon}, volume = {10}, number = {11}, pages = {e32020}, pmid = {38868076}, issn = {2405-8440}, abstract = {Nanotechnology has advanced significantly, particularly in biomedicine, showing promise for nanomaterial applications. Bacterial infections pose persistent public health challenges due to the lack of rapid pathogen detection methods, resulting in antibiotic overuse and bacterial resistance, threatening the human microbiome. Nanotechnology offers a solution through nanoparticle-based materials facilitating early bacterial detection and combating resistance. This study explores recent research on nanoparticle development for controlling microbial infections using various nanotechnology-driven detection methods. These approaches include Surface Plasmon Resonance (SPR) Sensors, Surface-Enhanced Raman Scattering (SERS) Sensors, Optoelectronic-based sensors, Bacteriophage-Based Sensors, and nanotechnology-based aptasensors. These technologies provide precise bacteria detection, enabling targeted treatment and infection prevention. Integrating nanoparticles into detection approaches holds promise for enhancing patient outcomes and mitigating harmful bacteria spread in healthcare settings.}, }
@article {pmid38866914, year = {2024}, author = {Heinzel, S and Jureczek, J and Kainulainen, V and Nieminen, AI and Suenkel, U and von Thaler, AK and Kaleta, C and Eschweiler, GW and Brockmann, K and Aho, VTE and Auvinen, P and Maetzler, W and Berg, D and Scheperjans, F}, title = {Elevated fecal calprotectin is associated with gut microbial dysbiosis, altered serum markers and clinical outcomes in older individuals.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {13513}, pmid = {38866914}, issn = {2045-2322}, support = {675915//Germany Research Society/ ; 310835//Research Council of Finland/ ; }, mesh = {Humans ; *Leukocyte L1 Antigen Complex/analysis/metabolism ; *Feces/microbiology/chemistry ; *Dysbiosis/diagnosis ; *Gastrointestinal Microbiome ; Aged ; Female ; Male ; *Biomarkers/blood/analysis ; Middle Aged ; Cohort Studies ; Inflammatory Bowel Diseases/blood/metabolism/microbiology ; }, abstract = {Fecal calprotectin is an established marker of gut inflammation in inflammatory bowel disease (IBD). Elevated levels of fecal calprotectin as well as gut microbial dysbiosis have also been observed in other clinical conditions. However, systemic and multi-omics alterations linked to elevated fecal calprotectin in older individuals remain unclear. This study comprehensively investigated the relationship between fecal calprotectin levels, gut microbiome composition, serum inflammation and targeted metabolomics markers, and relevant lifestyle and medical data in a large sample of older individuals (n = 735; mean age ± SD: 68.7 ± 6.3) from the TREND cohort study. Low (0-50 μg/g; n = 602), moderate (> 50-100 μg/g; n = 64) and high (> 100 μg/g; n = 62) fecal calprotectin groups were stratified. Several pro-inflammatory gut microbial genera were significantly increased and short-chain fatty acid producing genera were decreased in high vs. low calprotectin groups. In serum, IL-17C, CCL19 and the toxic metabolite indoxyl sulfate were increased in high vs. low fecal calprotectin groups. These changes were partially mediated by the gut microbiota. Moreover, the high fecal calprotectin group showed increased BMI and a higher disease prevalence of heart attack and obesity. Our findings contribute to the understanding of fecal calprotectin as a marker of gut dysbiosis and its broader systemic and clinical implications in older individuals.}, }
@article {pmid38862605, year = {2024}, author = {}, title = {The human microbiome and immune response shift during spaceflight.}, journal = {Nature microbiology}, volume = {9}, number = {7}, pages = {1640-1641}, pmid = {38862605}, issn = {2058-5276}, mesh = {*Space Flight ; Humans ; *Microbiota/immunology ; Immunity ; Weightlessness ; Gastrointestinal Microbiome/immunology ; }, }
@article {pmid38862604, year = {2024}, author = {Tierney, BT and Kim, J and Overbey, EG and Ryon, KA and Foox, J and Sierra, MA and Bhattacharya, C and Damle, N and Najjar, D and Park, J and Garcia Medina, JS and Houerbi, N and Meydan, C and Wain Hirschberg, J and Qiu, J and Kleinman, AS and Al-Ghalith, GA and MacKay, M and Afshin, EE and Dhir, R and Borg, J and Gatt, C and Brereton, N and Readhead, BP and Beyaz, S and Venkateswaran, KJ and Wiseman, K and Moreno, J and Boddicker, AM and Zhao, J and Lajoie, BR and Scott, RT and Altomare, A and Kruglyak, S and Levy, S and Church, GM and Mason, CE}, title = {Longitudinal multi-omics analysis of host microbiome architecture and immune responses during short-term spaceflight.}, journal = {Nature microbiology}, volume = {9}, number = {7}, pages = {1661-1675}, pmid = {38862604}, issn = {2058-5276}, support = {R01 CA249054/CA/NCI NIH HHS/United States ; R01 MH117406/MH/NIMH NIH HHS/United States ; NNX14AH50G//NASA | Johnson Space Center (JSC)/ ; NNX16AO69A//NASA | Johnson Space Center (JSC)/ ; R01MH117406//U.S. Department of Health &amp; Human Services | NIH | National Institute of Allergy and Infectious Diseases (NIAID)/ ; R01 ES032638/ES/NIEHS NIH HHS/United States ; R01 AI151059/AI/NIAID NIH HHS/United States ; }, mesh = {*Space Flight ; Humans ; Longitudinal Studies ; *Microbiota/immunology ; *Metagenomics ; *Astronauts ; *Bacteria/classification/genetics/immunology ; Male ; Gene Expression Profiling ; Adult ; Middle Aged ; Female ; Transcriptome ; Multiomics ; }, abstract = {Maintenance of astronaut health during spaceflight will require monitoring and potentially modulating their microbiomes. However, documenting microbial shifts during spaceflight has been difficult due to mission constraints that lead to limited sampling and profiling. Here we executed a six-month longitudinal study to quantify the high-resolution human microbiome response to three days in orbit for four individuals. Using paired metagenomics and metatranscriptomics alongside single-nuclei immune cell profiling, we characterized time-dependent, multikingdom microbiome changes across 750 samples and 10 body sites before, during and after spaceflight at eight timepoints. We found that most alterations were transient across body sites; for example, viruses increased in skin sites mostly during flight. However, longer-term shifts were observed in the oral microbiome, including increased plaque-associated bacteria (for example, Fusobacteriota), which correlated with immune cell gene expression. Further, microbial genes associated with phage activity, toxin-antitoxin systems and stress response were enriched across multiple body sites. In total, this study reveals in-depth characterization of microbiome and immune response shifts experienced by astronauts during short-term spaceflight and the associated changes to the living environment, which can help guide future missions, spacecraft design and space habitat planning.}, }
@article {pmid38862602, year = {2024}, author = {Osbelt, L and Almási, &#xc9;DH and Wende, M and Kienesberger, S and Voltz, A and Lesker, TR and Muthukumarasamy, U and Knischewski, N and Nordmann, E and Bielecka, AA and Giralt-Zúñiga, M and Kaganovitch, E and Kühne, C and Baier, C and Pietsch, M and Müsken, M and Greweling-Pils, MC and Breinbauer, R and Flieger, A and Schlüter, D and Müller, R and Erhardt, M and Zechner, EL and Strowig, T}, title = {Klebsiella oxytoca inhibits Salmonella infection through multiple microbiota-context-dependent mechanisms.}, journal = {Nature microbiology}, volume = {9}, number = {7}, pages = {1792-1811}, pmid = {38862602}, issn = {2058-5276}, support = {DOC 50/FWF_/Austrian Science Fund FWF/Austria ; 01KI1824//Joint Programming Initiative on Antimicrobial Resistance (Joint Programming Initiative for Antimicrobial Resistance)/ ; }, mesh = {*Klebsiella oxytoca/genetics/metabolism ; Animals ; Mice ; *Salmonella Infections/microbiology ; *Salmonella typhimurium/genetics/metabolism/growth &amp; development/drug effects ; Humans ; Disease Models, Animal ; Enterotoxins/metabolism/genetics ; Female ; Mice, Inbred C57BL ; Klebsiella Infections/microbiology ; Microbiota ; Gastrointestinal Microbiome ; Antibiosis ; Benzodiazepinones ; }, abstract = {The Klebsiella oxytoca species complex is part of the human microbiome, especially during infancy and childhood. K. oxytoca species complex strains can produce enterotoxins, namely, tilimycin and tilivalline, while also contributing to colonization resistance (CR). The relationship between these seemingly contradictory roles is not well understood. Here, by coupling ex vivo assays with CRISPR-mutagenesis and various mouse models, we show that K. oxytoca provides CR against Salmonella Typhimurium. In vitro, the antimicrobial activity against various Salmonella strains depended on tilimycin production and was induced by various simple carbohydrates. In vivo, CR against Salmonella depended on toxin production in germ-free mice, while it was largely toxin-independent in mice with residual microbiota. This was linked to the relative levels of toxin-inducing carbohydrates in vivo. Finally, dulcitol utilization was essential for toxin-independent CR in gnotobiotic mice. Together, this demonstrates that nutrient availability is key to both toxin-dependent and substrate-driven competition between K. oxytoca and Salmonella.}, }
@article {pmid38855423, year = {2024}, author = {Zhang, L and Wu, R and Ma, T and Fu, W and Chen, J and Li, L and He, Q}, title = {Investigation on the Therapeutic Mechanism of Danbie Capsules for Endometriosis: A Network Pharmacology Approach.}, journal = {International journal of general medicine}, volume = {17}, number = {}, pages = {2557-2574}, pmid = {38855423}, issn = {1178-7074}, abstract = {OBJECTIVE: To explore the active substances and targets of Danbie Capsules in Endometriosis therapy.<br><br>METHODS: This study was conducted through TCMSP and published literature screened and obtained 183 active substances of Danbie Capsules, combined and intersected with Endometriosis target genes collected and screened in the GEO database, obtained 24 target genes for Endometriosis treatment, and mapped the target network map of Danbie Capsules active substances against Endometriosis. The network was analyzed with the aid of Cytoscape version 3.9.1. With the aid of the platform of the STRING data analysis, PPI network analysis was conducted on 24 anti-Endometriosis targets of the Danbie Capsules.<br><br>RESULTS: The research results obtained three critical active substances, namely, Quercetin, &#x3b2;-sitosterol, and Luteolin. Seven critical targets were identified, and two representative genes (TP53 and AKT1) have been verified in Macromolecular docking and immunohistochemical verification.<br><br>CONCLUSION: The active substances of Danbie Capsules in the treatment of Endometriosis are Quercetin, &#x3b2;-sitosterol and Luteolin, and the main targets are TP53 and AKT1.}, }
@article {pmid38854053, year = {2024}, author = {Byrne, SR and DeMott, MS and Yuan, Y and Ghanegolmohammadi, F and Kaiser, S and Fox, JG and Alm, EJ and Dedon, PC}, title = {Temporal dynamics and metagenomics of phosphorothioate epigenomes in the human gut microbiome.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {38854053}, issn = {2692-8205}, support = {P30 DK043351/DK/NIDDK NIH HHS/United States ; P30 ES002109/ES/NIEHS NIH HHS/United States ; T32 ES007020/ES/NIEHS NIH HHS/United States ; }, abstract = {BACKGROUND: Epigenetic regulation of gene expression and host defense is well established in microbial communities, with dozens of DNA modifications comprising the epigenomes of prokaryotes and bacteriophage. Phosphorothioation (PT) of DNA, in which a chemically-reactive sulfur atom replaces a non-bridging oxygen in the sugar-phosphate backbone, is catalyzed by dnd and ssp gene families widespread in bacteria and archaea. However, little is known about the role of PTs or other microbial epigenetic modifications in the human microbiome. Here we optimized and applied fecal DNA extraction, mass spectrometric, and metagenomics technologies to characterize the landscape and temporal dynamics of gut microbes possessing PT modifications.<br><br>RESULTS: Exploiting the nuclease-resistance of PTs, mass spectrometric analysis of limit digests of PT-containing DNA reveals PT dinucleotides as part of genomic consensus sequences, with 16 possible dinucleotide combinations. Analysis of mouse fecal DNA revealed a highly uniform spectrum of 11 PT dinucleotides in all littermates, with PTs estimated to occur in 5-10% of gut microbes. Though at similar levels, PT dinucleotides in fecal DNA from 11 healthy humans possessed signature combinations and levels of individual PTs. Comparison with a widely distributed microbial epigenetic mark, m[6]dA, suggested temporal dynamics consistent with expectations for gut microbial communities based on Taylor's Power Law. Application of PT-seq for site-specific metagenomic analysis of PT-containing bacteria in one fecal donor revealed the larger consensus sequences for the PT dinucleotides in Bacteroidota, Firmicutes, Actinobacteria, and Proteobacteria, which differed from unbiased metagenomics and suggested that the abundance of PT-containing bacteria did not simply mirror the spectrum of gut bacteria. PT-seq further revealed low abundance PT sites not detected as dinucleotides by mass spectrometry, attesting to the complementarity of the technologies.<br><br>CONCLUSIONS: The results of our studies provide a benchmark for understanding the behavior of an abundant and chemically-reactive epigenetic mark in the human gut microbiome, with implications for inflammatory conditions of the gut.}, }
@article {pmid38850297, year = {2024}, author = {Hoisington, AJ and Stamper, CE and Ellis, JC and Lowry, CA and Brenner, LA}, title = {Quantifying variation across 16S rRNA gene sequencing runs in human microbiome studies.}, journal = {Applied microbiology and biotechnology}, volume = {108}, number = {1}, pages = {367}, pmid = {38850297}, issn = {1432-0614}, support = {U.S. Department of Veterans Affairs//U.S. Department of Veterans Affairs/ ; 140755//Mindsource Brain Injury Network/ ; }, mesh = {Humans ; *RNA, Ribosomal, 16S/genetics ; *Feces/microbiology ; *Microbiota/genetics ; *Sequence Analysis, DNA/methods ; *DNA, Bacterial/genetics ; Bacteria/genetics/classification/isolation &amp; purification ; Reproducibility of Results ; Mouth/microbiology ; High-Throughput Nucleotide Sequencing/methods ; }, abstract = {Recent microbiome research has incorporated a higher number of samples through more participants in a study, longitudinal studies, and metanalysis between studies. Physical limitations in a sequencing machine can result in samples spread across sequencing runs. Here we present the results of sequencing nearly 1000 16S rRNA gene sequences in fecal (stabilized and swab) and oral (swab) samples from multiple human microbiome studies and positive controls that were conducted with identical standard operating procedures. Sequencing was performed in the same center across 18 different runs. The simplified mock community showed limitations in accuracy, while precision (e.g., technical variation) was robust for the mock community and actual human positive control samples. Technical variation was the lowest for stabilized fecal samples, followed by fecal swab samples, and then oral swab samples. The order of technical variation stability was inverse of DNA concentrations (e.g., highest in stabilized fecal samples), highlighting the importance of DNA concentration in reproducibility and urging caution when analyzing low biomass samples. Coefficients of variation at the genus level also followed the same trend for lower variation with higher DNA concentrations. Technical variation across both sample types and the two human sampling locations was significantly less than the observed biological variation. Overall, this research providing comparisons between technical and biological variation, highlights the importance of using positive controls, and provides semi-quantified data to better understand variation introduced by sequencing runs. KEY POINTS: • Mock community and positive control accuracy were lower than precision. • Samples with lower DNA concentration had increased technical variation across sequencing runs. • Biological variation was significantly higher than technical variation due to sequencing runs.}, }
@article {pmid38849871, year = {2024}, author = {Lu, W and Aihaiti, A and Abudukeranmu, P and Liu, Y and Gao, H}, title = {Unravelling the role of intratumoral bacteria in digestive system cancers: current insights and future perspectives.}, journal = {Journal of translational medicine}, volume = {22}, number = {1}, pages = {545}, pmid = {38849871}, issn = {1479-5876}, mesh = {Humans ; *Digestive System Neoplasms/microbiology/therapy ; *Bacteria/metabolism ; Gastrointestinal Microbiome ; Animals ; }, abstract = {Recently, research on the human microbiome, especially concerning the bacteria within the digestive system, has substantially advanced. This exploration has unveiled a complex interplay between microbiota and health, particularly in the context of disease. Evidence suggests that the gut microbiome plays vital roles in digestion, immunity and the synthesis of vitamins and neurotransmitters, highlighting its significance in maintaining overall health. Conversely, disruptions in these microbial communities, termed dysbiosis, have been linked to the pathogenesis of various diseases, including digestive system cancers. These bacteria can influence cancer progression through mechanisms such as DNA damage, modulation of the tumour microenvironment, and effects on the host's immune response. Changes in the composition and function within the tumours can also impact inflammation, immune response and cancer therapy effectiveness. These findings offer promising avenues for the clinical application of intratumoral bacteria for digestive system cancer treatment, including the potential use of microbial markers for early cancer detection, prognostication and the development of microbiome-targeted therapies to enhance treatment outcomes. This review aims to provide a comprehensive overview of the pivotal roles played by gut microbiome bacteria in the development of digestive system cancers. Additionally, we delve into the specific contributions of intratumoral bacteria to digestive system cancer development, elucidating potential mechanisms and clinical implications. Ultimately, this review underscores the intricate interplay between intratumoral bacteria and digestive system cancers, underscoring the pivotal role of microbiome research in transforming diagnostic, prognostic and therapeutic paradigms for digestive system cancers.}, }
@article {pmid38849503, year = {2024}, author = {Kingsley, SF and Seo, Y and Wood, A and Wani, KA and Gonzalez, X and Irazoqui, J and Finkel, SE and Tissenbaum, HA}, title = {Glucose-fed microbiota alters C. elegans intestinal epithelium and increases susceptibility to multiple bacterial pathogens.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {13177}, pmid = {38849503}, issn = {2045-2322}, support = {R01 GM101056/GM/NIGMS NIH HHS/United States ; R35 GM149284/GM/NIGMS NIH HHS/United States ; W911NF1210321//U.S. Army Research Office/ ; 5R21AG067317//National Institutes of Aging,United States/ ; }, mesh = {*Caenorhabditis elegans/microbiology ; Animals ; *Glucose/metabolism ; *Intestinal Mucosa/microbiology/metabolism ; *Gastrointestinal Microbiome ; *Escherichia coli ; Reactive Oxygen Species/metabolism ; Longevity ; Disease Susceptibility ; }, abstract = {Overconsumption of dietary sugar can lead to many negative health effects including the development of Type 2 diabetes, metabolic syndrome, cardiovascular disease, and neurodegenerative disorders. Recently, the human intestinal microbiota, strongly associated with our overall health, has also been known to be affected by diet. However, mechanistic insight into the importance of the human intestinal microbiota and the effects of chronic sugar ingestion has not been possible largely due to the complexity of the human microbiome which contains hundreds of types of organisms. Here, we use an interspecies C. elegans/E. coli system, where E. coli are subjected to high sugar, then consumed by the bacterivore host C. elegans to become the microbiota. This glucose-fed microbiota results in a significant lifespan reduction accompanied by reduced healthspan (locomotion), reduced stress resistance, and changes in behavior and feeding. Lifespan reduction is also accompanied by two potential major contributors: increased intestinal bacterial density and increased concentration of reactive oxygen species. The glucose-fed microbiota accelerated the age-related development of intestinal cell permeability, intestinal distention, and dysregulation of immune effectors. Ultimately, the changes in the intestinal epithelium due to aging with the glucose-fed microbiota results in increased susceptibility to multiple bacterial pathogens. Taken together, our data reveal that chronic ingestion of sugar, such as a Western diet, has profound health effects on the host due to changes in the microbiota and may contribute to the current increased incidence of ailments including inflammatory bowel diseases as well as multiple age-related diseases.}, }
@article {pmid38846023, year = {2024}, author = {Jones, J and Murphy, CP and Sleator, RD and Culligan, EP}, title = {An exploratory in silico analysis of bacteriocin gene clusters in the urobiome.}, journal = {Microbiome research reports}, volume = {3}, number = {2}, pages = {24}, pmid = {38846023}, issn = {2771-5965}, abstract = {Background: The role of the urobiome in health and disease remains an understudied area compared to the rest of the human microbiome. Enhanced culturing techniques and next-generation sequencing technologies have identified the urobiome as an untapped source of potentially novel antimicrobials. The aim of this study was to screen the urobiome for genes encoding bacteriocin production. Methods: The genomes of 181 bacterial urobiome isolates were screened in silico for the presence of bacteriocin gene clusters using the bacteriocin mining tool BAGEL4 and secondary metabolite screening tool antiSMASH7. Results: From these isolates, an initial 263 areas of interest were identified, manually annotated, and evaluated for potential bacteriocin gene clusters. This resulted in 32 isolates containing 80 potential bacteriocin gene clusters, of which 72% were identified as class II, 13.75% as class III, 8.75% as class I, and 5% as unclassified bacteriocins. Conclusion: Overall, 53 novel variants were discovered, including nisin, gassericin, ubericin, and colicins.}, }
@article {pmid38843312, year = {2024}, author = {Davison, C and Tallman, S and de Ste-Croix, M and Antonio, M and Oggioni, MR and Kwambana-Adams, B and Freund, F and Beleza, S}, title = {Long-term evolution of Streptococcus mitis and Streptococcus pneumoniae leads to higher genetic diversity within rather than between human populations.}, journal = {PLoS genetics}, volume = {20}, number = {6}, pages = {e1011317}, pmid = {38843312}, issn = {1553-7404}, mesh = {*Streptococcus mitis/genetics ; Humans ; *Streptococcus pneumoniae/genetics ; *Genetic Variation ; *Evolution, Molecular ; *Genome, Bacterial ; Phylogeny ; Genetics, Population ; }, abstract = {Evaluation of the apportionment of genetic diversity of human bacterial commensals within and between human populations is an important step in the characterization of their evolutionary potential. Recent studies showed a correlation between the genomic diversity of human commensal strains and that of their host, but the strength of this correlation and of the geographic structure among human populations is a matter of debate. Here, we studied the genomic diversity and evolution of the phylogenetically related oro-nasopharyngeal healthy-carriage Streptococcus mitis and Streptococcus pneumoniae, whose lifestyles range from stricter commensalism to high pathogenic potential. A total of 119 S. mitis genomes showed higher within- and among-host variation than 810 S. pneumoniae genomes in European, East Asian and African populations. Summary statistics of the site-frequency spectrum for synonymous and non-synonymous variation and ABC modelling showed this difference to be due to higher ancestral bacterial population effective size (Ne) in S. mitis, whose genomic variation has been maintained close to mutation-drift equilibrium across (at least many) generations, whereas S. pneumoniae has been expanding from a smaller ancestral bacterial population. Strikingly, both species show limited differentiation among human populations. As genetic differentiation is inversely proportional to the product of effective population size and migration rate (Nem), we argue that large Ne have led to similar differentiation patterns, even if m is very low for S. mitis. We conclude that more diversity within than among human populations and limited population differentiation must be common features of the human microbiome due to large Ne.}, }
@article {pmid38841413, year = {2024}, author = {Manrique, P and Montero, I and Fernandez-Gosende, M and Martinez, N and Cantabrana, CH and Rios-Covian, D}, title = {Past, present, and future of microbiome-based therapies.}, journal = {Microbiome research reports}, volume = {3}, number = {2}, pages = {23}, pmid = {38841413}, issn = {2771-5965}, abstract = {Technological advances in studying the human microbiome in depth have enabled the identification of microbial signatures associated with health and disease. This confirms the crucial role of microbiota in maintaining homeostasis and the host health status. Nowadays, there are several ways to modulate the microbiota composition to effectively improve host health; therefore, the development of therapeutic treatments based on the gut microbiota is experiencing rapid growth. In this review, we summarize the influence of the gut microbiota on the development of infectious disease and cancer, which are two of the main targets of microbiome-based therapies currently being developed. We analyze the two-way interaction between the gut microbiota and traditional drugs in order to emphasize the influence of gut microbial composition on drug effectivity and treatment response. We explore the different strategies currently available for modulating this ecosystem to our benefit, ranging from 1st generation intervention strategies to more complex 2nd generation microbiome-based therapies and their regulatory framework. Lastly, we finish with a quick overview of what we believe is the future of these strategies, that is 3rd generation microbiome-based therapies developed with the use of artificial intelligence (AI) algorithms.}, }
@article {pmid38838470, year = {2024}, author = {Matharu, D and Ponsero, AJ and Lengyel, M and Meszaros-Matwiejuk, A and Kolho, KL and de Vos, WM and Molnar-Gabor, D and Salonen, A}, title = {Human milk oligosaccharide composition is affected by season and parity and associates with infant gut microbiota in a birth mode dependent manner in a Finnish birth cohort.}, journal = {EBioMedicine}, volume = {104}, number = {}, pages = {105182}, pmid = {38838470}, issn = {2352-3964}, mesh = {Humans ; *Milk, Human/chemistry/metabolism ; *Gastrointestinal Microbiome ; *Oligosaccharides/metabolism/analysis ; Female ; Finland ; Infant ; *Parity ; *Seasons ; Birth Cohort ; Metagenomics/methods ; Pregnancy ; Infant, Newborn ; Adult ; Metagenome ; Male ; Feces/microbiology ; }, abstract = {BACKGROUND: Human milk oligosaccharides (HMOs), their determinants, infant gut microbiota and health are under extensive research; however, seldom jointly addressed. Leveraging data from the HELMi birth cohort, we investigated them collectively, considering maternal and infant secretor status.<br><br>METHODS: HMO composition in breastmilk collected 3 months postpartum (n&#xa0;=&#xa0;350 mothers) was profiled using high-performance liquid chromatography. Infant gut microbiota taxonomic and functional development was studied at 3, 6, and 12 months (n&#xa0;=&#xa0;823 stool samples) via shotgun metagenomic sequencing, focusing on HMO metabolism via glycoside hydrolase (GH) analysis. Maternal and infant secretor statuses were identified through phenotyping and genotyping, respectively. Child health, emphasizing allergies and antibiotics as proxies for infectious diseases, was recorded until 2 years.<br><br>FINDINGS: Mother's parity, irritable bowel syndrome, gestational diabetes, and season of milk collection associated with HMO composition. Neither maternal nor infant secretor status associated with infant gut microbiota, except for a few taxa linked to individual HMOs. Analysis stratified for birth mode revealed distinct patterns between the infant gut microbiota and HMOs. Child health parameters were not associated to infant or maternal secretor status.<br><br>INTERPRETATION: This comprehensive exploration unveils intricate links between secretor genotype, maternal factors, HMO composition, infant microbiota, and child health. Understanding these nuanced relationships is paramount for refining strategies to optimize early life nutrition and its enduring impact on long-term health.<br><br>FUNDING: Sweet Crosstalk EU H2020 MSCA ITN, Academy of Finland, Mary and Georg C. Ehrnrooth Foundation, P&#xe4;ivikki and Sakari Sohlberg Foundation, and Tekes.}, }
@article {pmid38830891, year = {2024}, author = {Lopes, W and Amor, DR and Gore, J}, title = {Cooperative growth in microbial communities is a driver of multistability.}, journal = {Nature communications}, volume = {15}, number = {1}, pages = {4709}, pmid = {38830891}, issn = {2041-1723}, mesh = {*Microbiota/physiology ; Humans ; *Microbial Interactions ; Bacteria/genetics/classification/metabolism/growth &amp; development ; Glutamic Acid/metabolism ; Models, Biological ; Coculture Techniques ; }, abstract = {Microbial communities often exhibit more than one possible stable composition for the same set of external conditions. In the human microbiome, these persistent changes in species composition and abundance are associated with health and disease states, but the drivers of these alternative stable states remain unclear. Here we experimentally demonstrate that a cross-kingdom community, composed of six species relevant to the respiratory tract, displays four alternative stable states each dominated by a different species. In pairwise coculture, we observe widespread bistability among species pairs, providing a natural origin for the multistability of the full community. In contrast with the common association between bistability and antagonism, experiments reveal many positive interactions within and between community members. We find that multiple species display cooperative growth, and modeling predicts that this could drive the observed multistability within the community as well as non-canonical pairwise outcomes. A biochemical screening reveals that glutamate either reduces or eliminates cooperativity in the growth of several species, and we confirm that such supplementation reduces the extent of bistability across pairs and reduces multistability in the full community. Our findings provide a mechanistic explanation of how cooperative growth rather than competitive interactions can underlie multistability in microbial communities.}, }
@article {pmid38830853, year = {2024}, author = {Kitsios, GD and Sayed, K and Fitch, A and Yang, H and Britton, N and Shah, F and Bain, W and Evankovich, JW and Qin, S and Wang, X and Li, K and Patel, A and Zhang, Y and Radder, J and Dela Cruz, C and Okin, DA and Huang, CY and Van Tyne, D and Benos, PV and Methé, B and Lai, P and Morris, A and McVerry, BJ}, title = {Longitudinal multicompartment characterization of host-microbiota interactions in patients with acute respiratory failure.}, journal = {Nature communications}, volume = {15}, number = {1}, pages = {4708}, pmid = {38830853}, issn = {2041-1723}, support = {COVID-19 Respiratory Virus Research//American Lung Association (Lung Association)/ ; IK2 BX004886/BX/BLRD VA/United States ; IK2BX004886//U.S. Department of Veterans Affairs (Department of Veterans Affairs)/ ; P01 HL114453/HL/NHLBI NIH HHS/United States ; T32 HL116275/HL/NHLBI NIH HHS/United States ; R03 HL162655/HL/NHLBI NIH HHS/United States ; }, mesh = {Humans ; Female ; Male ; *Dysbiosis/microbiology ; Middle Aged ; *Lung/microbiology ; *COVID-19/microbiology/virology ; Aged ; *Microbiota/genetics ; *Gastrointestinal Microbiome/genetics ; Host Microbial Interactions/genetics ; Longitudinal Studies ; RNA, Ribosomal, 16S/genetics ; Respiratory Insufficiency/microbiology ; SARS-CoV-2/genetics/isolation &amp; purification ; Adult ; Respiration, Artificial ; Bacteria/genetics/classification/isolation &amp; purification ; Critical Illness ; Metagenomics/methods ; }, abstract = {Critical illness can significantly alter the composition and function of the human microbiome, but few studies have examined these changes over time. Here, we conduct a comprehensive analysis of the oral, lung, and gut microbiota in 479 mechanically ventilated patients (223 females, 256 males) with acute respiratory failure. We use advanced DNA sequencing technologies, including Illumina amplicon sequencing (utilizing 16S and ITS rRNA genes for bacteria and fungi, respectively, in all sample types) and Nanopore metagenomics for lung microbiota. Our results reveal a progressive dysbiosis in all three body compartments, characterized by a reduction in microbial diversity, a decrease in beneficial anaerobes, and an increase in pathogens. We find that clinical factors, such as chronic obstructive pulmonary disease, immunosuppression, and antibiotic exposure, are associated with specific patterns of dysbiosis. Interestingly, unsupervised clustering of lung microbiota diversity and composition by 16S independently predicted survival and performed better than traditional clinical and host-response predictors. These observations are validated in two separate cohorts of COVID-19 patients, highlighting the potential of lung microbiota as valuable prognostic biomarkers in critical care. Understanding these microbiome changes during critical illness points to new opportunities for microbiota-targeted precision medicine interventions.}, }
@article {pmid38828147, year = {2024}, author = {Tan, J and Zhang, J and Hu, C and Wang, G and Ren, Q and Wang, C and Dan, J and Zeng, Z and Hu, J and Zhu, W and Liang, J and Cai, J and Liu, Y and Yan, G and Lin, Y}, title = {Pharmacokinetic enhancement of oncolytic virus M1 by inhibiting JAK‒STAT pathway.}, journal = {Acta pharmaceutica Sinica. B}, volume = {14}, number = {6}, pages = {2554-2566}, pmid = {38828147}, issn = {2211-3835}, abstract = {Oncolytic viruses (OVs), a group of replication-competent viruses that can selectively infect and kill cancer cells while leaving healthy cells intact, are emerging as promising living anticancer agents. Unlike traditional drugs composed of non-replicating compounds or biomolecules, the replicative nature of viruses confer unique pharmacokinetic properties that require further studies. Despite some pharmacokinetics studies of OVs, mechanistic insights into the connection between OV pharmacokinetics and antitumor efficacy remain vague. Here, we characterized the pharmacokinetic profile of oncolytic virus M1 (OVM) in immunocompetent mouse tumor models and identified the JAK‒STAT pathway as a key modulator of OVM pharmacokinetics. By suppressing the JAK‒STAT pathway, early OVM pharmacokinetics are ameliorated, leading to enhanced tumor-specific viral accumulation, increased AUC and Cmax, and improved antitumor efficacy. Rather than compromising antitumor immunity after JAK‒STAT inhibition, the improved pharmacokinetics of OVM promotes T cell recruitment and activation in the tumor microenvironment, providing an optimal opportunity for the therapeutic outcome of immune checkpoint blockade, such as anti-PD-L1. Taken together, this study advances our understanding of the pharmacokinetic-pharmacodynamic relationship in OV therapy.}, }
@article {pmid38826830, year = {2024}, author = {Sahle, Z and Engidaye, G and Shenkute Gebreyes, D and Adenew, B and Abebe, TA}, title = {Fecal microbiota transplantation and next-generation therapies: A review on targeting dysbiosis in metabolic disorders and beyond.}, journal = {SAGE open medicine}, volume = {12}, number = {}, pages = {20503121241257486}, pmid = {38826830}, issn = {2050-3121}, abstract = {The human microbiome, particularly the gut microbiome, has emerged as a central determinant of health and disease. Dysbiosis, an imbalance in the microbial composition of the gut, is associated with a variety of metabolic and other diseases, highlighting the potential for microbiota-targeted treatments. Fecal microbiota transplantation has received considerable attention as a promising therapy to modulate the gut microbiome and restore microbial homeostasis. However, challenges remain, including standardization, safety, and long-term efficacy. This review summarizes current knowledge on fecal microbiota transplantation and describes the next generation therapies targeting microbiome. This review looked at the mechanistic understanding of fecal microbiota transplantation and alternative strategies, elucidating their potential role in improving dysbiosis-associated metabolic disorders, such as obesity, and type 2 diabetes and others. Additionally, this review discussed the growing application of therapies targeting the gut microbiome. Insights from clinical trials, preclinical studies, and emerging technologies provide a comprehensive overview of the evolving landscape of microbiome-based interventions. Through a critical assessment of current advances and prospects, this review aims to highlight the therapeutic potential of targeting gut microbiome and pave the way for innovative approaches in precision medicine and personalized treatments.}, }
@article {pmid38823201, year = {2024}, author = {Kasperek, MC and Velasquez Galeas, A and Caetano-Silva, ME and Xie, Z and Ulanov, A and La Frano, M and Devkota, S and Miller, MJ and Allen, JM}, title = {Microbial aromatic amino acid metabolism is modifiable in fermented food matrices to promote bioactivity.}, journal = {Food chemistry}, volume = {454}, number = {}, pages = {139798}, doi = {10.1016/j.foodchem.2024.139798}, pmid = {38823201}, issn = {1873-7072}, mesh = {Humans ; *Fermented Foods/analysis/microbiology ; *Fermentation ; *Amino Acids, Aromatic/metabolism ; *Receptors, Aryl Hydrocarbon/metabolism ; Lactobacillales/metabolism ; Lactates/metabolism ; }, abstract = {Ingestion of fermented foods impacts human immune function, yet the bioactive food components underlying these effects are not understood. Here, we interrogated whether fermented food bioactivity relates to microbial metabolites derived from aromatic amino acids, termed aryl-lactates. Using targeted metabolomics, we established the presence of aryl-lactates in commercially available fermented foods. After pinpointing fermented food-associated lactic acid bacteria that produce high levels of aryl-lactates, we identified fermentation conditions to increase aryl-lactate production in food matrices up to 5 × 10[3] fold vs. standard fermentation conditions. Using ex vivo reporter assays, we found that food matrix conditions optimized for aryl-lactate production exhibited enhanced agonist activity for the human aryl-hydrocarbon receptor (AhR) as compared to standard fermentation conditions and commercial products. Reduced microbial-induced AhR activity has emerged as a hallmark of many chronic inflammatory diseases, thus we envision strategies to enhance AhR bioactivity of fermented foods to be leveraged to improve human health.}, }
@article {pmid38820745, year = {2024}, author = {Haange, SB and Riesbeck, S and Aldehoff, AS and Engelmann, B and Jensen Pedersen, K and Castaneda-Monsalve, V and Rolle-Kampczyk, U and von Bergen, M and Jehmlich, N}, title = {Chemical mixture effects on the simplified human intestinal microbiota: Assessing xenobiotics at environmentally realistic concentrations.}, journal = {Journal of hazardous materials}, volume = {474}, number = {}, pages = {134683}, doi = {10.1016/j.jhazmat.2024.134683}, pmid = {38820745}, issn = {1873-3336}, mesh = {Humans ; *Xenobiotics/toxicity/metabolism ; *Fluorocarbons/toxicity ; *Gastrointestinal Microbiome/drug effects ; *Fatty Acids, Volatile/metabolism ; *Benzhydryl Compounds/toxicity ; Phenols/toxicity ; Bioreactors ; Sulfones/toxicity ; Environmental Pollutants/toxicity ; }, abstract = {The microbial community present in our intestines is pivotal for converting indigestible substances into vital nutrients and signaling molecules such as short-chain fatty acids (SCFAs). These compounds have considerable influence over our immune system and the development of diverse human diseases. However, ingested environmental contaminants, known as xenobiotics, can upset the delicate balance of the microbial gut community and enzymatic processes, consequently affecting the host organism. In our study, we employed an in vitro bioreactor model system based on the simplified human microbiome model (SIHUMIx) to investigate the direct effects of specific xenobiotics, such as perfluorooctanoic acid (PFOA), perfluorohexanoic acid (PFHxA) and perfluorobutanoic acid (PFBA) or bisphenol S (BPS) and bisphenol F (BPF), either individually or in combination, on the microbiota. We observed increased SCFA production, particularly acetate and butyrate, with PFAS exposure. Metaproteomics revealed pathway alterations across treatments, including changes in vitamin synthesis and fatty acid metabolism with BPX. This study underscores the necessity of assessing the combined effects of xenobiotics to better safeguard public health. It emphasizes the significance of considering adverse effects on the microbiome in the risk assessment of environmental chemicals.}, }
@article {pmid38819500, year = {2024}, author = {Solasaari, T and Korpela, K and Lommi, S and Hyvönen, S and Gardemeister, S and Merras-Salmio, L and Salonen, A and de Vos, WM and Kolho, KL}, title = {Bowel function in a prospective cohort of 1052 healthy term infants up to 4 months of age.}, journal = {European journal of pediatrics}, volume = {183}, number = {8}, pages = {3557-3565}, pmid = {38819500}, issn = {1432-1076}, support = {32510//the Academy of Finland/ ; 5851//the Finnish Medical Foundation/ ; 5044//Signe and Ane Gyllenberg Foundation/ ; 329/31/2015//Tekes/ ; }, mesh = {Humans ; *Defecation/physiology ; Prospective Studies ; Infant ; Male ; Female ; *Breast Feeding/statistics &amp; numerical data ; Infant, Newborn ; Feces/chemistry ; Surveys and Questionnaires ; Infant Formula ; Crying/physiology ; }, abstract = {The purpose of this study is to describe the defecation pattern of healthy infants up to 17 weeks of age. We included 1052 healthy term infants from the prospective HELMi cohort (NCT03996304). Parents filled in recurring online questionnaires on feeding, gastrointestinal function, and crying weekly for the first 17 weeks of life. Defecation frequency was highest at the age of 3 weeks (a median of 4 times/day, interquartile range (IQR) 2.9-5). At each time point, the median defecation frequency of breastfed infants was higher than that of infants receiving formula (e.g., at week 17 a median of 2 times/day, IQR 0.9-3.6, and a median of 1.1, IQR 0.6-1.4, respectively). The dominant color of the stool was most often yellow or light brown. Nearly black stools were reported in the first week of life in 3.4%. Nearly half (47.4%) of the infants had green stool color dominating for at least 1 week, with comparable frequency among breastfed (47.7%) and formula-fed (45.2%) infants. Green stools were associated with a higher defecation frequency (linear mixed-effect model p < 0.0001). Occasional blood in stool was reported in 9.3% and recurrent blood in 5.2% of the infants with no difference in stool consistency. Hard stools were rare (≤ 1%). Conclusion: This study enlightens the spectrum of defecation patterns in healthy term infants during the first 17 weeks of life. A better understanding of bowel function helps healthcare professionals distinguish normal from abnormal when addressing defecation, the color of stools, and the type of feeding. What is Known: • Breastfed infants have more frequent and more yellow-colored stools than formula-fed infants. • Stools with green color are often suggested by the parents or even by medical professionals to indicate disease or discomfort in early life. What is New: • Nearly half of the healthy term infants had green stool dominating for at least one week during the first 17 weeks and occasional blood was reported in almost 10% of the infants during this period. • Data on normal variation in bowel function and stool may serve primary health care professionals when educating the families and caretakers of infants.}, }
@article {pmid38818295, year = {2024}, author = {Efremova, I and Maslennikov, R and Poluektova, E and Medvedev, O and Kudryavtseva, A and Krasnov, G and Fedorova, M and Romanikhin, F and Zharkova, M and Zolnikova, O and Bagieva, G and Ivashkin, V}, title = {Presepsin as a biomarker of bacterial translocation and an indicator for the prescription of probiotics in cirrhosis.}, journal = {World journal of hepatology}, volume = {16}, number = {5}, pages = {822-831}, pmid = {38818295}, issn = {1948-5182}, abstract = {BACKGROUND: The gut-liver axis and bacterial translocation are important in cirrhosis, but there is no available universal biomarker of cellular bacterial translocation, for which presepsin may be a candidate.<br><br>AIM: To evaluate the relationship of the blood presepsin levels with the state of the gut microbiota in cirrhosis in the absence of obvious infection.<br><br>METHODS: This study included 48 patients with Child-Pugh cirrhosis classes B and C and 15 healthy controls. The fecal microbiome was assessed using 16S rRNA gene sequencing. Plasma levels of presepsin were measured. A total of 22 patients received a probiotic (Saccharomyces boulardii) for 3 months.<br><br>RESULTS: Presepsin levels were higher in patients with cirrhosis than in healthy individuals [342 (91-2875) vs 120 (102-141) pg/mL; P = 0.048]. Patients with elevated presepsin levels accounted for 56.3% of all included patients. They had lower levels of serum albumin and higher levels of serum total bilirubin and overall severity of cirrhosis as assessed using the Child-Pugh scale. Patients with elevated presepsin levels had an increased abundance of the main taxa responsible for bacterial translocation, namely Bacilli and Proteobacteria (including the main class Gammaproteobacteria and the minor taxa Xanthobacteraceae and Stenotrophomonas), and a low abundance of bacteria from the family Lachnospiraceae (including the minor genus Fusicatenibacter), which produce short-chain fatty acids that have a positive effect on intestinal barrier function. The presepsin level directly correlated with the relative abundance of Bacilli, Proteobacteria, and inversely correlated with the abundance of Lachnospiraceae and Propionibacteriaceae. After 3 months of taking the probiotic, the severity of cirrhosis on the Child-Pugh scale decreased significantly only in the group with elevated presepsin levels [from 9 (8-11) to 7 (6-9); P = 0.004], while there were no significant changes in the group with normal presepsin levels [from 8 (7-8) to 7 (6-8); P = 0.123]. A high level of presepsin before the prescription of the probiotic was an independent predictor of a greater decrease in Child-Pugh scores (P = 0.046), as well as a higher level of the Child-Pugh scale (P = 0.042), but not the C-reactive protein level (P = 0.679) according to multivariate linear regression analysis.<br><br>CONCLUSION: The level of presepsin directly correlates with the abundance in the gut microbiota of the main taxa that are substrates of bacterial translocation in cirrhosis. This biomarker, in the absence of obvious infection, seems important for assessing the state of the gut-liver axis in cirrhosis and deciding on therapy targeted at the gut microbiota in this disease.}, }
@article {pmid38817603, year = {2024}, author = {Warren, A and Nyavor, Y and Zarabian, N and Mahoney, A and Frame, LA}, title = {The microbiota-gut-brain-immune interface in the pathogenesis of neuroinflammatory diseases: a narrative review of the emerging literature.}, journal = {Frontiers in immunology}, volume = {15}, number = {}, pages = {1365673}, pmid = {38817603}, issn = {1664-3224}, mesh = {Humans ; *Gastrointestinal Microbiome/immunology ; Animals ; *Brain-Gut Axis/immunology ; *Neuroinflammatory Diseases/immunology/microbiology/etiology ; *Brain/immunology/microbiology ; }, abstract = {IMPORTANCE: Research is beginning to elucidate the sophisticated mechanisms underlying the microbiota-gut-brain-immune interface, moving from primarily animal models to human studies. Findings support the dynamic relationships between the gut microbiota as an ecosystem (microbiome) within an ecosystem (host) and its intersection with the host immune and nervous systems. Adding this to the effects on epigenetic regulation of gene expression further complicates and strengthens the response. At the heart is inflammation, which manifests in a variety of pathologies including neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, and Multiple Sclerosis (MS).<br><br>OBSERVATIONS: Generally, the research to date is limited and has focused on bacteria, likely due to the simplicity and cost-effectiveness of 16s rRNA sequencing, despite its lower resolution and inability to determine functional ability/alterations. However, this omits all other microbiota including fungi, viruses, and phages, which are emerging as key members of the human microbiome. Much of the research has been done in pre-clinical models and/or in small human studies in more developed parts of the world. The relationships observed are promising but cannot be considered reliable or generalizable at this time. Specifically, causal relationships cannot be determined currently. More research has been done in Alzheimer's disease, followed by Parkinson's disease, and then little in MS. The data for MS is encouraging despite this.<br><br>CONCLUSIONS AND RELEVANCE: While the research is still nascent, the microbiota-gut-brain-immune interface may be a missing link, which has hampered our progress on understanding, let alone preventing, managing, or putting into remission neurodegenerative diseases. Relationships must first be established in humans, as animal models have been shown to poorly translate to complex human physiology and environments, especially when investigating the human gut microbiome and its relationships where animal models are often overly simplistic. Only then can robust research be conducted in humans and using mechanistic model systems.}, }
@article {pmid38814902, year = {2024}, author = {Ezra, S and Bashan, A}, title = {Network impact of a single-time-point microbial sample.}, journal = {PloS one}, volume = {19}, number = {5}, pages = {e0301683}, pmid = {38814902}, issn = {1932-6203}, mesh = {Humans ; *Microbiota ; Female ; Pregnancy ; Diabetes, Gestational/microbiology ; }, abstract = {The human microbiome plays a crucial role in determining our well-being and can significantly influence human health. The individualized nature of the microbiome may reveal host-specific information about the health state of the subject. In particular, the microbiome is an ecosystem shaped by a tangled network of species-species and host-species interactions. Thus, analysis of the ecological balance of microbial communities can provide insights into these underlying interrelations. However, traditional methods for network analysis require many samples, while in practice only a single-time-point microbial sample is available in clinical screening. Recently, a method for the analysis of a single-time-point sample, which evaluates its 'network impact' with respect to a reference cohort, has been applied to analyze microbial samples from women with Gestational Diabetes Mellitus. Here, we introduce different variations of the network impact approach and systematically study their performance using simulated 'samples' fabricated via the Generalized Lotka-Volttera model of ecological dynamics. We show that the network impact of a single sample captures the effect of the interactions between the species, and thus can be applied to anomaly detection of shuffled samples, which are 'normal' in terms of species abundance but 'abnormal' in terms of species-species interrelations. In addition, we demonstrate the use of the network impact in binary and multiclass classifications, where the reference cohorts have similar abundance profiles but different species-species interactions. Individualized analysis of the human microbiome has the potential to improve diagnosis and personalized treatments.}, }
@article {pmid38811534, year = {2024}, author = {Elzinga, J and Narimatsu, Y and de Haan, N and Clausen, H and de Vos, WM and Tytgat, HLP}, title = {Binding of Akkermansia muciniphila to mucin is O-glycan specific.}, journal = {Nature communications}, volume = {15}, number = {1}, pages = {4582}, pmid = {38811534}, issn = {2041-1723}, support = {737.016.003//Nederlandse Organisatie voor Wetenschappelijk Onderzoek (Netherlands Organisation for Scientific Research)/ ; 024.002.002//Nederlandse Organisatie voor Wetenschappelijk Onderzoek (Netherlands Organisation for Scientific Research)/ ; Spinoza Grant Willem M de Vos//Nederlandse Organisatie voor Wetenschappelijk Onderzoek (Netherlands Organisation for Scientific Research)/ ; FEMS-GO-2021-069//Federation of European Microbiological Societies (FEMS)/ ; 0071658//Novo Nordisk Fonden (Novo Nordisk Foundation)/ ; NA//Lundbeckfonden (Lundbeck Foundation)/ ; GlycoSkin H2020-ERC; 772735//EC | EU Framework Programme for Research and Innovation H2020 | H2020 Priority Excellent Science | H2020 European Research Council (H2020 Excellent Science - European Research Council)/ ; }, mesh = {*Akkermansia/metabolism ; Humans ; *Mucins/metabolism ; *Polysaccharides/metabolism ; Neuraminidase/metabolism ; Protein Binding ; Glycosylation ; Disaccharides/metabolism ; Verrucomicrobia/metabolism ; Epitopes/metabolism ; Bacterial Adhesion ; }, abstract = {The intestinal anaerobic bacterium Akkermansia muciniphila is specialized in the degradation of mucins, which are heavily O-glycosylated proteins that constitute the major components of the mucus lining the intestine. Despite that adhesion to mucins is considered critical for the persistence of A. muciniphila in the human intestinal tract, our knowledge of how this intestinal symbiont recognizes and binds to mucins is still limited. Here, we first show that the mucin-binding properties of A. muciniphila are independent of environmental oxygen concentrations and not abolished by pasteurization. We then dissected the mucin-binding properties of pasteurized A. muciniphila by use of a recently developed cell-based mucin array that enables display of the tandem repeats of human mucins with distinct O-glycan patterns and structures. We found that A. muciniphila recognizes the unsialylated LacNAc (Galβ1-4GlcNAcβ1-R) disaccharide selectively on core2 and core3 O-glycans. This disaccharide epitope is abundantly found on human colonic mucins capped by sialic acids, and we demonstrated that endogenous A. muciniphila neuraminidase activity can uncover the epitope and promote binding. In summary, our study provides insights into the mucin-binding properties important for colonization of a key mucin-foraging bacterium.}, }
@article {pmid38809163, year = {2024}, author = {Chang, CJ and Liu, B and Liebmann, JM and Cioffi, GA and Winn, BJ}, title = {Glaucoma and the Human Microbiome.}, journal = {Journal of glaucoma}, volume = {33}, number = {8}, pages = {529-538}, doi = {10.1097/IJG.0000000000002448}, pmid = {38809163}, issn = {1536-481X}, mesh = {Humans ; *Glaucoma/microbiology/physiopathology ; *Microbiota/physiology ; Intraocular Pressure/physiology ; Dysbiosis ; Gastrointestinal Microbiome/physiology ; }, abstract = {PURPOSE OF REVIEW: To explore a view of the human microbiome as an interconnected, functional, dynamic system that may be linked to the pathogenesis and progression of glaucoma.<br><br>METHODS: A literature review was undertaken that included publications from 1966 to 2023.<br><br>RESULTS: Bacterial lipopolysaccharides (LPS) activate toll-like receptors (TLR) and mediate the human immune response. The LPS-TLR4 pathway is a potential avenue for the ocular, gut, and oral microbiomes to interface and/or influence ocular disease. Studies of gut dysbiosis have shown that alterations in the healthy microbiota can predispose the host to immune-mediated inflammatory and neurodegenerative conditions, while oral and ocular surface dysbiosis has been correlated with glaucoma. While developmental exposure to commensal microflora has shown to be necessary for the autoimmune and neurodegenerative responses to elevated intraocular pressure to take place, commensal bacterial products like short-chain fatty acids have regulatory effects protective against glaucoma.<br><br>SUMMARY: Alterations to human microbiotas have been associated with changes in intestinal permeability, gene regulation, immune cell differentiation, and neural functioning, which may predispose the host to glaucoma. Select microbes have been highlighted for their potential contributions to glaucoma disease progression or protection, raising the potential for microbiota-based treatment modalities. Current topical glaucoma treatments may disrupt the ocular surface microbiota, potentially having ramifications on host health. Further study of the relationships between human microbiome and glaucoma is needed.}, }
@article {pmid38809053, year = {2024}, author = {Selma-Royo, M and Ricci, L and Golzato, D and Servais, C and Nabinejad, A and Armanini, F and Asnicar, F and Pinto, F and Tamburini, S and Segata, N}, title = {Draft genome sequences of multiple bacterial strains isolated from human feces.}, journal = {Microbiology resource announcements}, volume = {13}, number = {7}, pages = {e0030724}, pmid = {38809053}, issn = {2576-098X}, abstract = {Bacterial isolation is necessary for functional and mechanistic analyses, and the increased human microbiome diversity revealed by metagenomic sequencing is expanding the relevant cultivation targets. Here, we report 46 draft genome sequences of bacterial isolates obtained from fecal samples of healthy adults in Trento and Milan (Italy), including strains from seven taxonomically uncharacterized species.}, }
@article {pmid38808120, year = {2024}, author = {Wang, T and Li, L and Figeys, D and Liu, YY}, title = {Pairing metagenomics and metaproteomics to characterize ecological niches and metabolic essentiality of gut microbiomes.}, journal = {ISME communications}, volume = {4}, number = {1}, pages = {ycae063}, pmid = {38808120}, issn = {2730-6151}, support = {U01 HL089856/HL/NHLBI NIH HHS/United States ; }, abstract = {The genome of a microorganism encodes its potential functions that can be implemented through expressed proteins. It remains elusive how a protein's selective expression depends on its metabolic essentiality to microbial growth or its ability to claim resources as ecological niches. To reveal a protein's metabolic or ecological role, we developed a computational pipeline, which pairs metagenomics and metaproteomics data to quantify each protein's gene-level and protein-level functional redundancy simultaneously. We first illustrated the idea behind the pipeline using simulated data of a consumer-resource model. We then validated it using real data from human and mouse gut microbiome samples. In particular, we analyzed ABC-type transporters and ribosomal proteins, confirming that the metabolic and ecological roles predicted by our pipeline agree well with prior knowledge. Finally, we performed in vitro cultures of a human gut microbiome sample and investigated how oversupplying various sugars involved in ecological niches influences the community structure and protein abundance. The presented results demonstrate the performance of our pipeline in identifying proteins' metabolic and ecological roles, as well as its potential to help us design nutrient interventions to modulate the human microbiome.}, }
@article {pmid38806600, year = {2024}, author = {Kwon, KM and Kim, EH and Sim, KH and Lee, YJ and Kang, EJ and Han, KH and Jin, JS and Kim, DK and Ahn, JH and Hwang, IH}, title = {Phenylacetic acid, an anti-vaginitis metabolite produced by the vaginal symbiotic bacterium Chryseobacterium gleum.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {12226}, pmid = {38806600}, issn = {2045-2322}, support = {2017R1D1A3B06035312//National Research Foundation of Korea/ ; 2020R1I1A3073660//National Research Foundation of Korea/ ; 2017R1C1B5073761//National Research Foundation of Korea/ ; }, mesh = {Female ; Animals ; *Phenylacetates/metabolism/pharmacology ; *Vagina/microbiology ; Mice ; Humans ; *Chryseobacterium/metabolism ; Candida albicans/metabolism/drug effects ; Symbiosis ; Hydrogen-Ion Concentration ; Gardnerella vaginalis/metabolism/drug effects ; Disease Models, Animal ; Vaginitis/microbiology/metabolism/drug therapy ; }, abstract = {The human microbiome contains genetic information that regulates metabolic processes in response to host health and disease. While acidic vaginal pH is maintained in normal conditions, the pH level increases in infectious vaginitis. We propose that this change in the vaginal environment triggers the biosynthesis of anti-vaginitis metabolites. Gene expression levels of Chryseobacterium gleum, a vaginal symbiotic bacterium, were found to be affected by pH changes. The distinctive difference in the metabolic profiles between two C. gleum cultures incubated under acidic and neutral pH conditions was suggested to be an anti-vaginitis molecule, which was identified as phenylacetic acid (PAA) by spectroscopic data analysis. The antimicrobial activity of PAA was evaluated in vitro, showing greater toxicity toward Gardnerella vaginalis and Candida albicans, two major vaginal pathogens, relative to commensal Lactobacillus spp. The activation of myeloperoxidase, prostaglandin E2, and nuclear factor-κB, and the expression of cyclooxygenase-2 were reduced by an intravaginal administration of PAA in the vaginitis mouse model. In addition, PAA displayed the downregulation of mast cell activation. Therefore, PAA was suggested to be a messenger molecule that mediates interactions between the human microbiome and vaginal health.}, }
@article {pmid38805126, year = {2024}, author = {Mahoney, D}, title = {The Role of the Human Microbiome in Epithelial Ovarian Cancer.}, journal = {Advances in experimental medicine and biology}, volume = {1452}, number = {}, pages = {97-105}, pmid = {38805126}, issn = {0065-2598}, mesh = {Humans ; Female ; *Ovarian Neoplasms/microbiology ; *Carcinoma, Ovarian Epithelial/microbiology/pathology ; *Microbiota/physiology ; }, abstract = {Ovarian cancer is the fifth-leading cause of cancer deaths among women due to the absence of available screening methods to identify early disease. Thus, prevention and early disease detection investigations are of high priority, surrounding a critical window of opportunity to better understand important pathogenic mechanisms of disease progression. Microorganisms modulate molecular interactions in humans that can influence states of health and disease, including ovarian cancer. While the mechanisms of infectious microbial invasion that trigger the immune-inflammatory axis are well studied in cancer research, the complex interactions that promote the transition of noninfectious healthy microbes to pathobiont expansion are less understood. As traditional research has focused on the influences of infectious pathogens on ovarian cancer development and progression, the impact of noninfectious microbes has gained scientific attention. The objective of this chapter is to summarize current evidence on the role of microbiota in epithelial ovarian cancer throughout disease.}, }
@article {pmid38795687, year = {2024}, author = {Quesada, S and Rosso, AD and Mascardi, F and Soler-Rivero, V and Aguilera, P and Mascuka, SN and Boiro, A and Arenielo, E and Vijoditz, G and Ferreyra-Mufarregue, LR and Caputo, MF and Cimolai, MC and Coluccio Leskow, F and Penas-Steinhardt, A and Belforte, FS}, title = {Integrative analysis of systemic lupus erythematosus biomarkers: Role of fecal hsa-mir-223-3p and gut microbiota in transkingdom dynamics.}, journal = {Molecular immunology}, volume = {171}, number = {}, pages = {77-92}, doi = {10.1016/j.molimm.2024.05.004}, pmid = {38795687}, issn = {1872-9142}, mesh = {Humans ; *MicroRNAs/genetics ; *Lupus Erythematosus, Systemic/microbiology/immunology ; *Gastrointestinal Microbiome ; *Feces/microbiology ; Female ; Adult ; *Biomarkers/metabolism ; Male ; Middle Aged ; Immunosuppressive Agents/therapeutic use ; }, abstract = {Systemic lupus erythematosus (SLE) involves a florid set of clinical manifestations whose autoreactive origin is characterized by an overactivation of the immune system and the production of a large number of autoantibodies. Because it is a complex pathology with an inflammatory component, its pathogenesis is not yet fully understood, assuming both genetic and environmental predisposing factors. Currently, it is known that the role of the human microbiome is crucial in maintaining the transkingdom balance between commensal microorganisms and the immune system. In the present work we study the intestinal microbiota of Argentine patients with different stages of SLE receiving or not different treatments. Microbiota composition and fecal miRNAs were assessed by 16 S sequencing and qPCR. hsa-miR-223-3p, a miRNA involved in several inflammation regulation pathways, was found underexpressed in SLE patients without immunosuppressive treatment. In terms of microbiota there were clear differences in population structure (Weighted and Unweighted Unifrac distances, p-value <0.05) and core microbiome between cases and controls. In addition, Collinsella, Bifidobacterium, Streptococcus genera and aromatics degradation metabolisms were overrepresented in the SLE group. Medical treatment was also determinant as several microbial metabolic pathways were influenced by immunosuppressive therapy. Particularly, allantoin degradation metabolism was differentially expressed in the group of patients receiving immunosuppressants. Finally, we performed a logistic regression model (LASSO: least absolute shrinkage and selection operator) considering the expression levels of the fecal hsa-miR223-3p; the core microbiota; the differentially abundant bacterial taxa and the differentially abundant metabolic pathways (p<0.05). The model predicted that SLE patients could be associated with greater relative abundance of the formaldehyde oxidation pathway (RUMP_PWY). On the contrary, the preponderance of the ketodeoxyoctonate (Kdo) biosynthesis and activation route (PWY_1269) and the genera Lachnospiraceae_UCG_004, Lachnospira, Victivallis and UCG_003 (genus belonging to the family Oscillospiraceae of the class Clostridia) were associated with a control phenotype. Overall, the present work could contribute to the development of integral diagnostic tools for the comprehensive phenotyping of patients with SLE. In this sense, studying the commensal microbial profile and possible pathobionts associated with SLE in our population proposes more effective and precise strategies to explore possible treatments based on the microbiota of SLE patients.}, }
@article {pmid38792733, year = {2024}, author = {Putrino, A and Marinelli, E and Galeotti, A and Ferrazzano, GF and Ciribè, M and Zaami, S}, title = {A Journey into the Evolution of Human Host-Oral Microbiome Relationship through Ancient Dental Calculus: A Scoping Review.}, journal = {Microorganisms}, volume = {12}, number = {5}, pages = {}, pmid = {38792733}, issn = {2076-2607}, abstract = {One of the most promising areas of research in palaeomicrobiology is the study of the human microbiome. In particular, ancient dental calculus helps to reconstruct a substantial share of oral microbiome composition by mapping together human evolution with its state of health/oral disease. This review aims to trace microbial characteristics in ancient dental calculus to describe the evolution of the human host-oral microbiome relationship in oral health or disease in children and adults. Following the PRISMA-Extension for Scoping Reviews guidelines, the main scientific databases (PubMed, Scopus, Lilacs, Cochrane Library) have been drawn upon. Eligibility criteria were established, and all the data collected on a purpose-oriented collection form were analysed descriptively. From the initial 340 records, only 19 studies were deemed comprehensive enough for the purpose of this review. The knowledge of the composition of ancient oral microbiomes has broadened over the past few years thanks to increasingly well-performing decontamination protocols and additional analytical avenues. Above all, metagenomic sequencing, also implemented by state-of-the-art bioinformatics tools, allows for the determination of the qualitative-quantitative composition of microbial species associated with health status and caries/periodontal disease. Some microbial species, especially periodontal pathogens, do not appear to have changed in history, while others that support caries disease or oral health could be connected to human evolution through lifestyle and environmental contributing factors.}, }
@article {pmid38792577, year = {2024}, author = {Koo, H and Morrow, CD}, title = {Bacteroidales-Specific Antimicrobial Genes Can Influence the Selection of the Dominant Fecal Strain of Bacteroides vulgatus and Bacteroides uniformis from the Gastrointestinal Tract Microbial Community.}, journal = {Life (Basel, Switzerland)}, volume = {14}, number = {5}, pages = {}, pmid = {38792577}, issn = {2075-1729}, abstract = {Bacteroides vulgatus and Bacteroides uniformis are known to be abundant in the human fecal microbial community. Although these strains typically remain stable over time in humans, disruption of this microbial community following antibiotics resulted in the transient change to new strains suggesting that a complex, dynamic strain community exists in humans. To further study the selection of dominant fecal microbial strains from the gastrointestinal tract (GIT) community, we analyzed three longitudinal metagenomic sequencing data sets using BLAST+ to identify genes encoding Bacteroidales-specific antimicrobial proteins (BSAP) that have known functions to restrict species-specific replication of B. uniformis (BSAP-2) or B. vulgatus (BSAP-3) and have been postulated to provide a competitive advantage in microbial communities. In the HMP (Human Microbiome Project) data set, we found fecal samples from individuals had B. vulgatus or B. uniformis with either complete or deleted BSAP genes that did not change over time. We also examined fecal samples from two separate longitudinal data sets of individuals who had been given either single or multiple antibiotics. The BSAP gene pattern from most individuals given either single or multiple antibiotics recovered to be the same as the pre-antibiotic strain. However, in a few individuals, we found incomplete BSAP-3 genes at early times during the recovery that were replaced by B. vulgatus with the complete BSAP-3 gene, consistent with the function of the BSAP to specifically restrict Bacteroides spp. The results of these studies provide insights into the fluxes that occur in the Bacteroides spp. GIT community following perturbation and the dynamics of the selection of a dominant fecal strain of Bacteroides spp.}, }
@article {pmid38791599, year = {2024}, author = {Olteanu, G and Ciucă-Pană, MA and Busnatu, &#x218;S and Lupuliasa, D and Neacșu, SM and Mititelu, M and Musuc, AM and Ioniță-Mîndrican, CB and Boroghină, SC}, title = {Unraveling the Microbiome-Human Body Axis: A Comprehensive Examination of Therapeutic Strategies, Interactions and Implications.}, journal = {International journal of molecular sciences}, volume = {25}, number = {10}, pages = {}, pmid = {38791599}, issn = {1422-0067}, mesh = {Humans ; *Dysbiosis/microbiology/therapy ; *Gastrointestinal Microbiome ; *Fecal Microbiota Transplantation ; Microbiota ; Animals ; Human Body ; Host Microbial Interactions/physiology ; }, abstract = {This review scrutinizes the intricate interplay between the microbiome and the human body, exploring its multifaceted dimensions and far-reaching implications. The human microbiome, comprising diverse microbial communities inhabiting various anatomical niches, is increasingly recognized as a critical determinant of human health and disease. Through an extensive examination of current research, this review elucidates the dynamic interactions between the microbiome and host physiology across multiple organ systems. Key topics include the establishment and maintenance of microbiota diversity, the influence of host factors on microbial composition, and the bidirectional communication pathways between microbiota and host cells. Furthermore, we delve into the functional implications of microbiome dysbiosis in disease states, emphasizing its role in shaping immune responses, metabolic processes, and neurological functions. Additionally, this review discusses emerging therapeutic strategies aimed at modulating the microbiome to restore host-microbe homeostasis and promote health. Microbiota fecal transplantation represents a groundbreaking therapeutic approach in the management of dysbiosis-related diseases, offering a promising avenue for restoring microbial balance within the gut ecosystem. This innovative therapy involves the transfer of fecal microbiota from a healthy donor to an individual suffering from dysbiosis, aiming to replenish beneficial microbial populations and mitigate pathological imbalances. By synthesizing findings from diverse fields, this review offers valuable insights into the complex relationship between the microbiome and the human body, highlighting avenues for future research and clinical interventions.}, }
@article {pmid38791230, year = {2024}, author = {Pérez-Pérez, ME and Nieto-Torres, E and Bollain-Y-Goytia, JJ and Delgadillo-Ruíz, L}, title = {Protein Citrullination by Peptidyl Arginine Deiminase/Arginine Deiminase Homologs in Members of the Human Microbiota and Its Recognition by Anti-Citrullinated Protein Antibodies.}, journal = {International journal of molecular sciences}, volume = {25}, number = {10}, pages = {}, pmid = {38791230}, issn = {1422-0067}, support = {the F002 Support for scientific, technological and innovation activities//This work was supported by the F002 Support for scientific, technological and innovation activities. Zacatecas Council of Science./ ; }, mesh = {Adult ; Female ; Humans ; Male ; Middle Aged ; *Anti-Citrullinated Protein Antibodies/immunology/metabolism ; *Arthritis, Rheumatoid/immunology/microbiology ; Case-Control Studies ; *Citrullination ; Citrulline/metabolism ; Cross-Sectional Studies ; Hydrolases/metabolism ; *Microbiota ; Protein-Arginine Deiminase Type 2/metabolism ; Protein-Arginine Deiminase Type 4/metabolism ; *Protein-Arginine Deiminases/metabolism/genetics ; }, abstract = {The human microbiome exists throughout the body, and it is essential for maintaining various physiological processes, including immunity, and dysbiotic events, which are associated with autoimmunity. Peptidylarginine deiminase (PAD) enzymes can citrullinate self-proteins related to rheumatoid arthritis (RA) that induce the production of anti-citrullinated protein antibodies (ACPAs) and lead to inflammation and joint damage. The present investigation was carried out to demonstrate the expression of homologs of PADs or arginine deiminases (ADs) and citrullinated proteins in members of the human microbiota. To achieve the objective, we used 17 microbial strains and specific polyclonal antibodies (pAbs) of the synthetic peptide derived from residues 100-200 of human PAD2 (anti-PAD2 pAb), and the recombinant fragment of amino acids 326 and 611 of human PAD4 (anti-PAD4 pAb), a human anti-citrulline pAb, and affinity ACPAs of an RA patient. Western blot (WB), enzyme-linked immunosorbent assay (ELISA), elution, and a test with Griess reagent were used. This is a cross-sectional case-control study on patients diagnosed with RA and control subjects. Inferential statistics were applied using the non-parametric Kruskal-Wallis test and Mann-Whitney U test generated in the SPSS program. Some members of phyla Firmicutes and Proteobacteria harbor homologs of PADs/ADs and citrullinated antigens that are reactive to the ACPAs of RA patients. Microbial citrullinome and homolog enzymes of PADs/ADs are extensive in the human microbiome and are involved in the production of ACPAs. Our findings suggest a molecular link between microorganisms of a dysbiotic microbiota and RA pathogenesis.}, }
@article {pmid38788999, year = {2024}, author = {Filippo, D and Guardone, L and Listorti, V and Elisabetta, R}, title = {Microbiome in cancer: A comparative analysis between humans and dogs.}, journal = {Veterinary journal (London, England : 1997)}, volume = {305}, number = {}, pages = {106145}, doi = {10.1016/j.tvjl.2024.106145}, pmid = {38788999}, issn = {1532-2971}, mesh = {Dogs ; Animals ; Humans ; *Dog Diseases/microbiology ; *Neoplasms/veterinary/microbiology ; Gastrointestinal Microbiome ; Microbiota ; Dysbiosis/veterinary ; Female ; }, abstract = {Cancer is a major cause of death in humans and animals worldwide. While cancer survival rates have increased over recent decades, further research to identify risk factors for the onset and progression of disease, and safe and highly efficacious treatments, is needed. Spontaneous tumours in pets represent an excellent model for neoplastic disease in humans. In this regard, dogs are an interesting species, as the divergence between the dog and human genome is low, humans and dogs have important similarities in the development and functioning of the immune system, and both species often share the same physical environment. There is also a higher homology between the canine and human microbiome than murine model. This review aims to describe and organize recently published information on canine microbiome assemblages and their relationship with the onset and progression of colorectal cancer, breast cancer and lymphoma, and to compare this with human disease. In both species, dysbiosis can induce variations in the gut microbiota that strongly influence shifts in status between health and disease. This can produce an inflammatory state, potentially leading to neoplasia, especially in the intestine, thus supporting canine studies in comparative oncology. Intestinal dysbiosis can also alter the efficacy and side effects of cancer treatments. Fewer published studies are available on changes in the relevant microbiomes in canine lymphoma and mammary cancer, and further research in this area could improve our understanding of the role of microbiota in the development of these cancers.}, }
@article {pmid38788190, year = {2024}, author = {Mishra, AK and Mahmud, I and Lorenzi, PL and Jenq, RR and Wargo, JA and Ajami, NJ and Peterson, CB}, title = {TARO: tree-aggregated factor regression for microbiome data integration.}, journal = {Bioinformatics (Oxford, England)}, volume = {40}, number = {6}, pages = {}, pmid = {38788190}, issn = {1367-4811}, support = {R01 CA244845/CA/NCI NIH HHS/United States ; R01 HL158796/HL/NHLBI NIH HHS/United States ; R01 HL158796/NH/NIH HHS/United States ; }, mesh = {Humans ; *Microbiota ; Software ; Metabolomics/methods ; Colorectal Neoplasms/microbiology/metabolism ; Gastrointestinal Microbiome ; Algorithms ; }, abstract = {MOTIVATION: Although the human microbiome plays a key role in health and disease, the biological mechanisms underlying the interaction between the microbiome and its host are incompletely understood. Integration with other molecular profiling data offers an opportunity to characterize the role of the microbiome and elucidate therapeutic targets. However, this remains challenging to the high dimensionality, compositionality, and rare features found in microbiome profiling data. These challenges necessitate the use of methods that can achieve structured sparsity in learning cross-platform association patterns.<br><br>RESULTS: We propose Tree-Aggregated factor RegressiOn (TARO) for the integration of microbiome and metabolomic data. We leverage information on the taxonomic tree structure to flexibly aggregate rare features. We demonstrate through simulation studies that TARO accurately recovers a low-rank coefficient matrix and identifies relevant features. We applied TARO to microbiome and metabolomic profiles gathered from subjects being screened for colorectal cancer to understand how gut microrganisms shape intestinal metabolite abundances.<br><br>The R package TARO implementing the proposed methods is available online at https://github.com/amishra-stats/taro-package.}, }
@article {pmid38782975, year = {2024}, author = {McKee, K and Bassis, CM and Golob, J and Palazzolo, B and Sen, A and Comstock, SS and Rosas-Salazar, C and Stanford, JB and O'Connor, T and Gern, JE and Paneth, N and Dunlop, AL and , }, title = {Host factors are associated with vaginal microbiome structure in pregnancy in the ECHO Cohort Consortium.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {11798}, pmid = {38782975}, issn = {2045-2322}, support = {P30 ES010126/ES/NIEHS NIH HHS/United States ; U24OD023382//Environmental influences on Child Health Outcomes (ECHO) program, Office of the Director, National Institutes of Health/ ; U2C OD023375/OD/NIH HHS/United States ; UH3 OD023271/OD/NIH HHS/United States ; UH3 OD023282/OD/NIH HHS/United States ; UH3OD023282//Environmental influences on Child Health Outcomes (ECHO) program, Office of the Director, National Institutes of Health/ ; UH3 OD023287/OD/NIH HHS/United States ; U24 OD023319/OD/NIH HHS/United States ; UH3 OD023305/OD/NIH HHS/United States ; UH3 OD023288/OD/NIH HHS/United States ; UH3OD023249//Environmental influences on Child Health Outcomes (ECHO) program, Office of the Director, National Institutes of Health/ ; U24OD023319//Environmental influences on Child Health Outcomes (ECHO) program, Office of the Director, National Institutes of Health/ ; UH3 OD023349/OD/NIH HHS/United States ; UH3 OD023268/OD/NIH HHS/United States ; UH3 OD023337/OD/NIH HHS/United States ; UH3 OD023328/OD/NIH HHS/United States ; U24 OD023382/OD/NIH HHS/United States ; UH3 OD023313/OD/NIH HHS/United States ; UH3 OD023289/OD/NIH HHS/United States ; UH3 OD023249/OD/NIH HHS/United States ; UH3 OD023389/OD/NIH HHS/United States ; UH3 OD023290/OD/NIH HHS/United States ; UH3OD023251//Environmental influences on Child Health Outcomes (ECHO) program, Office of the Director, National Institutes of Health/ ; UH3 OD023285/OD/NIH HHS/United States ; UH3 OD023275/OD/NIH HHS/United States ; P30 ES001247/ES/NIEHS NIH HHS/United States ; UH3 OD023318/OD/NIH HHS/United States ; UH3 OD023248/OD/NIH HHS/United States ; U2COD023375//Environmental influences on Child Health Outcomes (ECHO) program, Office of the Director, National Institutes of Health/ ; UH3 OD023253/OD/NIH HHS/United States ; UH3 OD023272/OD/NIH HHS/United States ; UH3 OD023347/OD/NIH HHS/United States ; UH3OD023318//Environmental influences on Child Health Outcomes (ECHO) program, Office of the Director, National Institutes of Health/ ; UH3 OD023251/OD/NIH HHS/United States ; UH3 OD023279/OD/NIH HHS/United States ; UH3OD023285//Environmental influences on Child Health Outcomes (ECHO) program, Office of the Director, National Institutes of Health/ ; K01 AI153558/AI/NIAID NIH HHS/United States ; U19 AI104317/AI/NIAID NIH HHS/United States ; UH3 OD023244/OD/NIH HHS/United States ; UH3 OD023320/OD/NIH HHS/United States ; }, mesh = {Humans ; Female ; Pregnancy ; *Vagina/microbiology ; *Microbiota/genetics ; Adult ; *RNA, Ribosomal, 16S/genetics ; Cohort Studies ; Young Adult ; }, abstract = {Using pooled vaginal microbiota data from pregnancy cohorts (N = 683 participants) in the Environmental influences on Child Health Outcomes (ECHO) Program, we analyzed 16S rRNA gene amplicon sequences to identify clinical and demographic host factors that associate with vaginal microbiota structure in pregnancy both within and across diverse cohorts. Using PERMANOVA models, we assessed factors associated with vaginal community structure in pregnancy, examined whether host factors were conserved across populations, and tested the independent and combined effects of host factors on vaginal community state types (CSTs) using multinomial logistic regression models. Demographic and social factors explained a larger amount of variation in the vaginal microbiome in pregnancy than clinical factors. After adjustment, lower education, rather than self-identified race, remained a robust predictor of L. iners dominant (CST III) and diverse (CST IV) (OR = 8.44, 95% CI = 4.06-17.6 and OR = 4.18, 95% CI = 1.88-9.26, respectively). In random forest models, we identified specific taxonomic features of host factors, particularly urogenital pathogens associated with pregnancy complications (Aerococcus christensenii and Gardnerella spp.) among other facultative anaerobes and key markers of community instability (L. iners). Sociodemographic factors were robustly associated with vaginal microbiota structure in pregnancy and should be considered as sources of variation in human microbiome studies.}, }
@article {pmid38781679, year = {2024}, author = {Mangalea, MR and Halpin, AL and Haile, M and Elkins, CA and McDonald, LC}, title = {Decolonization and Pathogen Reduction Approaches to Prevent Antimicrobial Resistance and Healthcare-Associated Infections.}, journal = {Emerging infectious diseases}, volume = {30}, number = {6}, pages = {1069-1076}, pmid = {38781679}, issn = {1080-6059}, mesh = {Humans ; *Cross Infection/prevention &amp; control/microbiology ; *Drug Resistance, Bacterial ; *Anti-Bacterial Agents/pharmacology/therapeutic use ; Microbiota/drug effects ; Bacterial Infections/prevention &amp; control/microbiology ; Infection Control/methods ; Bacteria/drug effects ; }, abstract = {Antimicrobial resistance in healthcare-associated bacterial pathogens and the infections they cause are major public health threats affecting nearly all healthcare facilities. Antimicrobial-resistant bacterial infections can occur when colonizing pathogenic bacteria that normally make up a small fraction of the human microbiota increase in number in response to clinical perturbations. Such infections are especially likely when pathogens are resistant to the collateral effects of antimicrobial agents that disrupt the human microbiome, resulting in loss of colonization resistance, a key host defense. Pathogen reduction is an emerging strategy to prevent transmission of, and infection with, antimicrobial-resistant healthcare-associated pathogens. We describe the basis for pathogen reduction as an overall prevention strategy, the evidence for its effectiveness, and the role of the human microbiome in colonization resistance that also reduces the risk for infection once colonized. In addition, we explore ideal attributes of current and future pathogen-reducing approaches.}, }
@article {pmid38779566, year = {2024}, author = {Scanu, M and Toto, F and Petito, V and Masi, L and Fidaleo, M and Puca, P and Baldelli, V and Reddel, S and Vernocchi, P and Pani, G and Putignani, L and Scaldaferri, F and Del Chierico, F}, title = {An integrative multi-omic analysis defines gut microbiota, mycobiota, and metabolic fingerprints in ulcerative colitis patients.}, journal = {Frontiers in cellular and infection microbiology}, volume = {14}, number = {}, pages = {1366192}, pmid = {38779566}, issn = {2235-2988}, mesh = {Humans ; *Colitis, Ulcerative/microbiology/metabolism ; *Gastrointestinal Microbiome ; Male ; Adult ; Female ; *Bacteria/classification/isolation &amp; purification/metabolism/genetics ; Middle Aged ; *Metabolomics/methods ; *RNA, Ribosomal, 16S/genetics ; *Gas Chromatography-Mass Spectrometry ; *Feces/microbiology ; *Fungi/classification/isolation &amp; purification/metabolism ; Dysbiosis/microbiology ; Metabolome ; Aged ; Young Adult ; Solid Phase Microextraction ; Mycobiome ; Multiomics ; }, abstract = {BACKGROUND: Ulcerative colitis (UC) is a multifactorial chronic inflammatory bowel disease (IBD) that affects the large intestine with superficial mucosal inflammation. A dysbiotic gut microbial profile has been associated with UC. Our study aimed to characterize the UC gut bacterial, fungal, and metabolic fingerprints by omic approaches.<br><br>METHODS: The 16S rRNA- and ITS2-based metataxonomics and gas chromatography-mass spectrometry/solid phase microextraction (GC-MS/SPME) metabolomic analysis were performed on stool samples of 53 UC patients and 37 healthy subjects (CTRL). Univariate and multivariate approaches were applied to separated and integrated omic data, to define microbiota, mycobiota, and metabolic signatures in UC. The interaction between gut bacteria and fungi was investigated by network analysis.<br><br>RESULTS: In the UC cohort, we reported the increase of Streptococcus, Bifidobacterium, Enterobacteriaceae, TM7-3, Granulicatella, Peptostreptococcus, Lactobacillus, Veillonella, Enterococcus, Peptoniphilus, Gemellaceae, and phenylethyl alcohol; and we also reported the decrease of Akkermansia; Ruminococcaceae; Ruminococcus; Gemmiger; Methanobrevibacter; Oscillospira; Coprococus; Christensenellaceae; Clavispora; Vishniacozyma; Quambalaria; hexadecane; cyclopentadecane; 5-hepten-2-ol, 6 methyl; 3-carene; caryophyllene; p-Cresol; 2-butenal; indole, 3-methyl-; 6-methyl-3,5-heptadiene-2-one; 5-octadecene; and 5-hepten-2-one, 6 methyl. The integration of the multi-omic data confirmed the presence of a distinctive bacterial, fungal, and metabolic fingerprint in UC gut microbiota. Moreover, the network analysis highlighted bacterial and fungal synergistic and/or divergent interkingdom interactions.<br><br>CONCLUSION: In this study, we identified intestinal bacterial, fungal, and metabolic UC-associated biomarkers. Furthermore, evidence on the relationships between bacterial and fungal ecosystems provides a comprehensive perspective on intestinal dysbiosis and ecological interactions between microorganisms in the framework of UC.}, }
@article {pmid38778221, year = {2024}, author = {Chen, Z and Lin, K and Yu, H}, title = {Reply to Qiao et al.}, journal = {British journal of cancer}, volume = {130}, number = {12}, pages = {1889}, pmid = {38778221}, issn = {1532-1827}, }
@article {pmid38774631, year = {2024}, author = {Dorst, M and Zeevenhooven, N and Wilding, R and Mende, D and Brandt, BW and Zaura, E and Hoekstra, A and Sheraton, VM}, title = {FAIR compliant database development for human microbiome data samples.}, journal = {Frontiers in cellular and infection microbiology}, volume = {14}, number = {}, pages = {1384809}, pmid = {38774631}, issn = {2235-2988}, mesh = {Humans ; *Microbiota/genetics ; Databases, Factual ; Metadata ; Metagenome ; Information Dissemination ; Computational Biology/methods ; Metagenomics/methods ; Databases, Genetic ; }, abstract = {INTRODUCTION: Sharing microbiome data among researchers fosters new innovations and reduces cost for research. Practically, this means that the (meta)data will have to be standardized, transparent and readily available for researchers. The microbiome data and associated metadata will then be described with regards to composition and origin, in order to maximize the possibilities for application in various contexts of research. Here, we propose a set of tools and protocols to develop a real-time FAIR (Findable. Accessible, Interoperable and Reusable) compliant database for the handling and storage of human microbiome and host-associated data.<br><br>METHODS: The conflicts arising from privacy laws with respect to metadata, possible human genome sequences in the metagenome shotgun data and FAIR implementations are discussed. Alternate pathways for achieving compliance in such conflicts are analyzed. Sample traceable and sensitive microbiome data, such as DNA sequences or geolocalized metadata are identified, and the role of the GDPR (General Data Protection Regulation) data regulations are considered. For the construction of the database, procedures have been realized to make data FAIR compliant, while preserving privacy of the participants providing the data.<br><br>RESULTS AND DISCUSSION: An open-source development platform, Supabase, was used to implement the microbiome database. Researchers can deploy this real-time database to access, upload, download and interact with human microbiome data in a FAIR complaint manner. In addition, a large language model (LLM) powered by ChatGPT is developed and deployed to enable knowledge dissemination and non-expert usage of the database.}, }
@article {pmid38771520, year = {2024}, author = {Chaudhary, PP and Kaur, M and Myles, IA}, title = {Does "all disease begin in the gut"? The gut-organ cross talk in the microbiome.}, journal = {Applied microbiology and biotechnology}, volume = {108}, number = {1}, pages = {339}, pmid = {38771520}, issn = {1432-0614}, mesh = {Humans ; *Gastrointestinal Microbiome ; Microbiota ; Skin/microbiology ; Vagina/microbiology ; Lung/microbiology ; Mouth/microbiology ; Female ; Gastrointestinal Tract/microbiology ; }, abstract = {The human microbiome, a diverse ecosystem of microorganisms within the body, plays pivotal roles in health and disease. This review explores site-specific microbiomes, their role in maintaining health, and strategies for their upkeep, focusing on oral, lung, vaginal, skin, and gut microbiota, and their systemic connections. Understanding the intricate relationships between these microbial communities is crucial for unraveling mechanisms underlying human health. Recent research highlights bidirectional communication between the gut and distant microbiome sites, influencing immune function, metabolism, and disease susceptibility. Alterations in one microbiome can impact others, emphasizing their interconnectedness and collective influence on human physiology. The therapeutic potential of gut microbiota in modulating distant microbiomes offers promising avenues for interventions targeting various disorders. Through interdisciplinary collaboration and technological advancements, we can harness the power of the microbiome to revolutionize healthcare, emphasizing microbiome-centric approaches to promote holistic well-being while identifying areas for future research.}, }
@article {pmid38771144, year = {2024}, author = {Wang, P and Duan, F and Lv, Y and Man, S and Liu, S and Liu, Y}, title = {Long- and Intermediate-Term Ambient Particulate Pollution Is Associated with Increased Osteoarthritis Risk: A Population-Based Prospective Analysis.}, journal = {Environmental science &amp; technology}, volume = {58}, number = {22}, pages = {9536-9547}, doi = {10.1021/acs.est.3c10893}, pmid = {38771144}, issn = {1520-5851}, mesh = {Humans ; *Osteoarthritis/epidemiology ; *Particulate Matter ; Prospective Studies ; Air Pollution ; Male ; Air Pollutants ; Female ; Environmental Exposure ; Middle Aged ; Risk Factors ; Beijing/epidemiology ; Aged ; }, abstract = {Recent studies found the intrusion and retention of exogenous fine particles into joints, but epidemiological data for long- and intermediate-term exposure associations are scare. Here, all urban working, retired employee, and rural residents (16.78 million) in Beijing from January 1, 2011 to December 31, 2019 were included to investigate the effects of long- and intermediate-term ambient particulate exposure on development of osteoarthritis. We identified 1,742,067 participants as first-visit patients with osteoarthritis. For each interquartile range increase in annual PM2.5 (23.32 μg/m[3]) and PM10 (23.92 μg/m[3]) exposure concentration, the pooled hazard ratios were respectively 1.238 (95% CI: 1.228, 1.249) and 1.178 (95% CI: 1.168, 1.189) for first osteoarthritis outpatient visits. Moreover, age at first osteoarthritis outpatient visits significantly decreased by 4.52 (95% CI: 3.45 to 5.40) days per μg/m[3] for annual PM2.5 exposure at below 67.85 μg/m[3]. Finally, among the six constituents analyzed, black carbon appears to be the most important component associated with the association between PM2.5 exposure and the three osteoarthritis-related outcomes.}, }
@article {pmid38767067, year = {2024}, author = {Kalluçi, E and Preni, B and Dhamo, X and Noka, E and Bardhi, S and Macchia, A and Bonetti, G and Dhuli, K and Donato, K and Bertelli, M and Zambrano, LJM and Janaqi, S}, title = {A comparative study of supervised and unsupervised machine learning algorithms applied to human microbiome.}, journal = {La Clinica terapeutica}, volume = {175}, number = {3}, pages = {98-116}, doi = {10.7417/CT.2024.5051}, pmid = {38767067}, issn = {1972-6007}, mesh = {Humans ; *Supervised Machine Learning ; *Unsupervised Machine Learning ; *Microbiota/genetics ; *RNA, Ribosomal, 16S/genetics/analysis ; Colorectal Neoplasms/microbiology ; Gastrointestinal Microbiome/genetics ; Algorithms ; Feces/microbiology ; Adenoma/microbiology ; }, abstract = {BACKGROUND: The human microbiome, consisting of diverse bacte-rial, fungal, protozoan and viral species, exerts a profound influence on various physiological processes and disease susceptibility. However, the complexity of microbiome data has presented significant challenges in the analysis and interpretation of these intricate datasets, leading to the development of specialized software that employs machine learning algorithms for these aims.<br><br>METHODS: In this paper, we analyze raw data taken from 16S rRNA gene sequencing from three studies, including stool samples from healthy control, patients with adenoma, and patients with colorectal cancer. Firstly, we use network-based methods to reduce dimensions of the dataset and consider only the most important features. In addition, we employ supervised machine learning algorithms to make prediction.<br><br>RESULTS: Results show that graph-based techniques reduces dimen-sion from 255 up to 78 features with modularity score 0.73 based on different centrality measures. On the other hand, projection methods (non-negative matrix factorization and principal component analysis) reduce dimensions to 7 features. Furthermore, we apply supervised machine learning algorithms on the most important features obtained from centrality measures and on the ones obtained from projection methods, founding that the evaluation metrics have approximately the same scores when applying the algorithms on the entire dataset, on 78 feature and on 7 features.<br><br>CONCLUSIONS: This study demonstrates the efficacy of graph-based and projection methods in the interpretation for 16S rRNA gene sequencing data. Supervised machine learning on refined features from both approaches yields comparable predictive performance, emphasizing specific microbial features-bacteroides, prevotella, fusobacterium, lysinibacillus, blautia, sphingomonas, and faecalibacterium-as key in predicting patient conditions from raw data.}, }
@article {pmid38743245, year = {2024}, author = {de Moraes, DC and Rollin-Pinheiro, R and Pinto, MDCFR and Domingos, LTS and Barreto-Bergter, E and Ferreira-Pereira, A}, title = {Antifungal activity of β-lapachone against a fluconazole-resistant Candida auris strain.}, journal = {Brazilian journal of microbiology : [publication of the Brazilian Society for Microbiology]}, volume = {55}, number = {3}, pages = {2593-2601}, pmid = {38743245}, issn = {1678-4405}, support = {Bolsa de Pesquisa Produtividade//Universidade Est&#xe1;cio de S&#xe1;/ ; Financial Code 001//CAPES/ ; }, mesh = {*Naphthoquinones/pharmacology ; *Antifungal Agents/pharmacology ; *Drug Resistance, Fungal/drug effects ; *Microbial Sensitivity Tests ; *Fluconazole/pharmacology ; *Biofilms/drug effects ; Humans ; *Candida auris/drug effects/genetics ; Amphotericin B/pharmacology ; Candidiasis/microbiology/drug therapy ; }, abstract = {Candida spp. can be found in the human microbiome. However, immunocompromised patients are likely to develop invasive Candida infections, with mortality rates higher than 50%. The discovery of C. auris, a species that rapidly acquire antifungal resistance, increased the concern about Candida infections. The limited number of antifungal agents and the high incidence of resistance to them make imperative the development of new antifungal drugs. β-lapachone is a biological active naphthoquinone that displays antifungal activity against C. albicans and C. glabrata. The aim of this study was to evaluate if this substance affects C. auris growth and elucidate its mechanism of action. A fluconazole-resistant C. auris isolate was used in this study. The antifungal activity of β-lapachone was determined through microbroth dilution assays, and its mechanism of action was evaluated using fluorescent probes. Interaction with fluconazole and amphotericin B was assessed by disk diffusion assay and checkerboard. β-lapachone inhibited planktonic C. auris cell growth by 92.7%, biofilm formation by 84.9%, and decrease the metabolism of preformed biofilms by 87.1% at 100 µg/ml. At 100 µg/ml, reductions of 30% and 59% of Calcofluor White and Nile red fluorescences were observed, indicating that β-lapachone affects cell wall chitin and neutral lipids content, respectively. Also, the ratio 590 nm/529 nm of JC-1 decreased 52%, showing that the compound affects mitochondria. No synergism was observed between β-lapachone and fluconazole or amphotericin B. Data show that β-lapachone may be a promising candidate to be used as monotherapy to treat C. auris resistant infections.}, }
@article {pmid38740909, year = {2024}, author = {Han, S and Guiberson, ER and Li, Y and Sonnenburg, JL}, title = {High-throughput identification of gut microbiome-dependent metabolites.}, journal = {Nature protocols}, volume = {19}, number = {7}, pages = {2180-2205}, pmid = {38740909}, issn = {1750-2799}, support = {F32AG062119//U.S. Department of Health &amp; Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging)/ ; R01-DK085025//U.S. Department of Health &amp; Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (National Institute of Diabetes &amp; Digestive &amp; Kidney Diseases)/ ; 5T32AI007328-35//U.S. Department of Health &amp; Human Services | NIH | National Institute of Allergy and Infectious Diseases (NIAID)/ ; R01-DK101674//U.S. Department of Health &amp; Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (National Institute of Diabetes &amp; Digestive &amp; Kidney Diseases)/ ; }, mesh = {*Gastrointestinal Microbiome/physiology ; Humans ; *Metabolomics/methods ; Chromatography, Liquid/methods ; *Mass Spectrometry/methods ; Metabolome ; Computational Biology/methods ; Bacteria/metabolism ; }, abstract = {A significant hurdle that has limited progress in microbiome science has been identifying and studying the diverse set of metabolites produced by gut microbes. Gut microbial metabolism produces thousands of difficult-to-identify metabolites, which present a challenge to study their roles in host biology. In recent years, mass spectrometry-based metabolomics has become one of the core technologies for identifying small metabolites. However, metabolomics expertise, ranging from sample preparation to instrument use and data analysis, is often lacking in academic labs. Most targeted metabolomics methods provide high levels of sensitivity and quantification, while they are limited to a panel of predefined molecules that may not be informative to microbiome-focused studies. Here we have developed a gut microbe-focused and wide-spectrum metabolomic protocol using liquid chromatography-mass spectrometry and bioinformatic analysis. This protocol enables users to carry out experiments from sample collection to data analysis, only requiring access to a liquid chromatography-mass spectrometry instrument, which is often available at local core facilities. By applying this protocol to samples containing human gut microbial metabolites, spanning from culture supernatant to human biospecimens, our approach enables high-confidence identification of >800 metabolites that can serve as candidate mediators of microbe-host interactions. We expect this protocol will lower the barrier to tracking gut bacterial metabolism in vitro and in mammalian hosts, propelling hypothesis-driven mechanistic studies and accelerating our understanding of the gut microbiome at the chemical level.}, }
@article {pmid38740509, year = {2024}, author = {Paone, P and Latousakis, D and Terrasi, R and Vertommen, D and Jian, C and Borlandelli, V and Suriano, F and Johansson, MEV and Puel, A and Bouzin, C and Delzenne, NM and Salonen, A and Juge, N and Florea, BI and Muccioli, GG and Overkleeft, H and Van Hul, M and Cani, PD}, title = {Human milk oligosaccharide 2'-fucosyllactose protects against high-fat diet-induced obesity by changing intestinal mucus production, composition and degradation linked to changes in gut microbiota and faecal proteome profiles in mice.}, journal = {Gut}, volume = {73}, number = {10}, pages = {1632-1649}, pmid = {38740509}, issn = {1468-3288}, mesh = {Animals ; *Diet, High-Fat/adverse effects ; *Obesity/metabolism/microbiology/prevention &amp; control ; *Gastrointestinal Microbiome/drug effects ; *Trisaccharides/metabolism ; Mice ; *Feces/microbiology/chemistry ; Humans ; Milk, Human/metabolism/chemistry ; Intestinal Mucosa/metabolism ; Proteome/metabolism/analysis ; Mucus/metabolism ; Male ; Mice, Inbred C57BL ; Mucins/metabolism ; }, abstract = {OBJECTIVE: To decipher the mechanisms by which the major human milk oligosaccharide (HMO), 2'-fucosyllactose (2'FL), can affect body weight and fat mass gain on high-fat diet (HFD) feeding in mice. We wanted to elucidate whether 2'FL metabolic effects are linked with changes in intestinal mucus production and secretion, mucin glycosylation and degradation, as well as with the modulation of the gut microbiota, faecal proteome and endocannabinoid (eCB) system.<br><br>RESULTS: 2'FL supplementation reduced HFD-induced obesity and glucose intolerance. These effects were accompanied by several changes in the intestinal mucus layer, including mucus production and composition, and gene expression of secreted and transmembrane mucins, glycosyltransferases and genes involved in mucus secretion. In addition, 2'FL increased bacterial glycosyl hydrolases involved in mucin glycan degradation. These changes were linked to a significant increase and predominance of bacterial genera Akkermansia and Bacteroides, different faecal proteome profile (with an upregulation of proteins involved in carbon, amino acids and fat metabolism and a downregulation of proteins involved in protein digestion and absorption) and, finally, to changes in the eCB system. We also investigated faecal proteomes from lean and obese humans and found similar changes observed comparing lean and obese mice.<br><br>CONCLUSION: Our results show that the HMO 2'FL influences host metabolism by modulating the mucus layer, gut microbiota and eCB system and propose the mucus layer as a new potential target for the prevention of obesity and related disorders.}, }
@article {pmid38740275, year = {2024}, author = {Long, AR and Mortara, EL and Mendoza, BN and Fink, EC and Sacco, FX and Ciesla, MJ and Stack, TMM}, title = {Sequence similarity network analysis of drug- and dye-modifying azoreductase enzymes found in the human gut microbiome.}, journal = {Archives of biochemistry and biophysics}, volume = {757}, number = {}, pages = {110025}, pmid = {38740275}, issn = {1096-0384}, support = {P20 GM103430/GM/NIGMS NIH HHS/United States ; }, mesh = {Humans ; *Nitroreductases/metabolism/genetics ; *Gastrointestinal Microbiome ; *NADH, NADPH Oxidoreductases/metabolism/genetics/chemistry ; Coloring Agents/metabolism ; Molecular Docking Simulation ; Substrate Specificity ; Sulfasalazine ; Bacterial Proteins/metabolism/genetics/chemistry ; Kinetics ; Clostridiales/enzymology/genetics ; Azo Compounds/metabolism/chemistry ; }, abstract = {Drug metabolism by human gut microbes is often exemplified by azo bond reduction in the anticolitic prodrug sulfasalazine. Azoreductase activity is often found in incubations with cell cultures or ex vivo gut microbiome samples and contributes to the xenobiotic metabolism of drugs and food additives. Applying metagenomic studies to personalized medicine requires knowledge of the genes responsible for sulfasalazine and other drug metabolism, and candidate genes and proteins for drug modifications are understudied. A representative gut-abundant azoreductase from Anaerotignum lactatifermentan DSM 14214 efficiently reduces sulfasalazine and another drug, phenazopyridine, but could not reduce all azo-bonded drugs in this class. We used enzyme kinetics to characterize this enzyme for its NADH-dependent reduction of these drugs and food additives and performed computational docking to provide the groundwork for understanding substrate specificity in this family. We performed an analysis of the Flavodoxin-like fold InterPro family (IPR003680) by computing a sequence similarity network to classify distinct subgroups of the family and then performed chemically-guided functional profiling to identify proteins that are abundant in the NIH Human Microbiome Project dataset. This strategy aims to reduce the number of unique azoreductases needed to characterize one protein family in the diverse set of potential drug- and dye-modifying activities found in the human gut microbiome.}, }
@article {pmid38736265, year = {2024}, author = {Pang, Z and Korpela, R and Vapaatalo, H}, title = {Local aldosterone release and CYP11B2 expression in response to angiotensin peptides, glucose, and potassium - an ex vivo study on murine colon.}, journal = {Journal of physiology and pharmacology : an official journal of the Polish Physiological Society}, volume = {75}, number = {2}, pages = {185-194}, doi = {10.26402/jpp.2024.2.07}, pmid = {38736265}, issn = {1899-1505}, mesh = {Animals ; Male ; Mice ; *Aldosterone/metabolism ; Angiotensin I/physiology ; Angiotensin II/physiology ; Angiotensin III/physiology ; *Colon/metabolism/drug effects ; *Cytochrome P-450 CYP11B2/metabolism ; *Glucose/metabolism ; Peptide Fragments/physiology ; *Potassium/metabolism ; }, abstract = {We have previously described local aldosterone synthesis in mouse colon. In the renin-angiotensin-aldosterone system (RAAS), angiotensin II (Ang II) peptide is the physiological factor which stimulates aldosterone synthesis in the adrenal glands. We have recently demonstrated that Ang II stimulates aldosterone synthesis also in mouse colon. Here, we conducted a 75-min ex vivo incubation of murine colonic tissue and evaluated the effects of three other Ang peptides, Ang I (1 μM), Ang III (0.1 μM) and Ang (1-7) (0.1 μM) on aldosterone synthesis. As a possible mechanism, their effects on tissue levels of the rate-limiting enzyme, aldosterone synthase (CYP11B2) were measured by ELISA and Western blot. Ang III significantly elevated the amount of tissue CYP11B2 protein in colon. The values of released aldosterone in colon tissue incubation were increased over the control in the presence of Ang I, II or III, however, being statistically non-significant. In Western blot analysis, the values of tissue CYP11B2 protein content were elevated by Ang I and II. Ang (1-7) alone in colon did not influence CYP11B2 protein levels in the incubation experiment but showed higher aldosterone release without statistical significance. Ang (1-7) showed an antagonistic effect towards Ang II in release of aldosterone in adrenal gland. An overall estimation of a single peptide (three measured variables), the results were always in an increasing direction. The responses of aldosterone synthesis to high levels of glucose (44 mM) and potassium (18.8 mM) as physiological stimulators in vivo were investigated in the colon incubation. Glucose, equal to four times the concentration of the control buffer in the incubation, showed higher values of aldosterone release in colon than control without statistical significance similarly to the effect seen in adrenal glands. Increasing the concentration of potassium in the incubation buffer exerted no effect on colonic aldosterone production. Intriguingly, no correlation was found between aldosterone release and the tissue CYP11B2 protein content in colon. In summary, the response of colonic aldosterone synthesis to different Ang peptides resembles, but is not identical to, the situation in the adrenal glands.}, }
@article {pmid38734968, year = {2024}, author = {Ma, Y and Zhao, Y and Zhang, X}, title = {Factors affecting neutrophil functions during sepsis: human microbiome and epigenetics.}, journal = {Journal of leukocyte biology}, volume = {116}, number = {4}, pages = {672-688}, doi = {10.1093/jleuko/qiae107}, pmid = {38734968}, issn = {1938-3673}, mesh = {Humans ; *Neutrophils/immunology ; *Sepsis/immunology/microbiology/genetics ; *Epigenesis, Genetic ; *Microbiota/immunology ; *DNA Methylation ; Extracellular Traps/immunology ; }, abstract = {Sepsis is a severe disease that occurs when the body's immune system reacts excessively to infection. The body's response, which includes an intense antibacterial reaction, can damage its tissues and organs. Neutrophils are the major components of white blood cells in circulation, play a vital role in innate immunity while fighting against infections, and are considered a feature determining sepsis classification. There is a plethora of basic research detailing neutrophil functioning, among which, the study of neutrophil extracellular traps is providing novel insights into mechanisms and treatments of sepsis. This review explores their functions, dysfunctions, and influences in the context of sepsis. The interplay between neutrophils and the human microbiome and the impact of DNA methylation on neutrophil function in sepsis are crucial areas of study. The interaction between neutrophils and the human microbiome is complex, particularly in the context of sepsis, where dysbiosis may occur. We highlight the importance of deciphering neutrophils' functional alterations and their epigenetic features in sepsis because it is critical for defining sepsis endotypes and opening up the possibility for novel diagnostic methods and therapy. Specifically, epigenetic signatures are pivotal since they will provide a novel implication for a sepsis diagnostic method when used in combination with the cell-free DNA. Research is exploring how specific patterns of DNA methylation in neutrophils, detectable in cell-free DNA, could serve as biomarkers for the early detection of sepsis.}, }
@article {pmid38732595, year = {2024}, author = {Luiskari, L and Lindén, J and Lehto, M and Salmenkari, H and Korpela, R}, title = {Ketogenic Diet Protects from Experimental Colitis in a Mouse Model Regardless of Dietary Fat Source.}, journal = {Nutrients}, volume = {16}, number = {9}, pages = {}, pmid = {38732595}, issn = {2072-6643}, support = {N/A//Mary och Georg C. Ehrnrooths Stiftelse/ ; N/A//Finnish Cultural Foundation/ ; N/A//Finnish Concordia Fund/ ; N/A//Finska L&#xe4;kares&#xe4;llskapet/ ; #NNFOC0013659//Novo Nordisk Foundation/ ; N/A//Wilhelm and Else Stockmann Foundation/ ; }, mesh = {Animals ; *Diet, Ketogenic ; *Colitis/chemically induced/diet therapy ; Male ; *Mice, Inbred C57BL ; *Disease Models, Animal ; *Dextran Sulfate ; Mice ; *Dietary Fats/adverse effects ; *Colon/pathology/metabolism ; Permeability ; Tight Junction Proteins/metabolism ; Interleukin-1beta/metabolism ; Intestinal Mucosa/pathology/metabolism ; Tumor Necrosis Factor-alpha/metabolism ; Fatty Acids ; Dextrans ; Fluorescein-5-isothiocyanate/*analogs &amp; derivatives ; }, abstract = {While ketogenic diets (KDs) may have potential as adjunct treatments for gastrointestinal diseases, there is little knowledge on how the fat source of these diets impacts intestinal health. The objective of this study was to investigate how the source of dietary fat of KD influences experimental colitis. We fed nine-week-old male C57BL/6J mice (n = 36) with a low-fat control diet or KD high either in saturated fatty acids (SFA-KD) or polyunsaturated linoleic acid (LA-KD) for four weeks and then induced colitis with dextran sodium sulfate (DSS). To compare the diets, we analyzed macroscopic and histological changes in the colon, intestinal permeability to fluorescein isothiocyanate-dextran (FITC-dextran), and the colonic expression of tight junction proteins and inflammatory markers. While the effects were more pronounced with LA-KD, both KDs markedly alleviated DSS-induced histological lesions. LA-KD prevented inflammation-related weight loss and the shortening of the colon, as well as preserved Il1b and Tnf expression at a healthy level. Despite no significant between-group differences in permeability to FITC-dextran, LA-KD mitigated changes in tight junction protein expression. Thus, KDs may have preventive potential against intestinal inflammation, with the level of the effect being dependent on the dietary fat source.}, }
@article {pmid38729090, year = {2024}, author = {Richter, D and Piel, J}, title = {Novel types of RiPP-modifying enzymes.}, journal = {Current opinion in chemical biology}, volume = {80}, number = {}, pages = {102463}, doi = {10.1016/j.cbpa.2024.102463}, pmid = {38729090}, issn = {1879-0402}, mesh = {*Protein Processing, Post-Translational ; Humans ; *Peptides/metabolism/chemistry ; Ribosomes/metabolism ; Biological Products/metabolism/chemistry ; Animals ; Enzymes/metabolism/chemistry ; }, abstract = {Novel discoveries in natural product biosynthesis reveal hidden bioactive compounds and expand our knowledge in enzymology. Ribosomally synthesized and post-translationally modified peptides (RiPPs) are a rapidly growing class of natural products featuring diverse non-canonical amino acids introduced by maturation enzymes as a class-defining characteristic. Underexplored RiPP sources, such as the human microbiome, the oceans, uncultured microorganisms, and plants are rich hunting grounds for novel enzymology. Unusual α- and β-amino acids, peptide cleavages, lipidations, diverse macrocyclizations, and other features expand the range of chemical groups that are installed in RiPPs by often promiscuous enzymes. This review highlights the search for novelty in RiPP enzymology in the past two years, with respect to the discovery of new biochemical modifications but also towards novel applications.}, }
@article {pmid38718217, year = {2024}, author = {Nicholson, LK and Kofonow, JM and Robertson, CE and Wright, T and Li, Q and Gardner, EM and Frank, DN and Janoff, EN}, title = {Clinical and Microbial Determinants of Upper Respiratory Colonization With Streptococcus pneumoniae and Native Microbiota in People With Human Immunodeficiency Virus Type 1 and Control Adults.}, journal = {The Journal of infectious diseases}, volume = {230}, number = {6}, pages = {1456-1465}, pmid = {38718217}, issn = {1537-6613}, support = {R01 AI108479/AI/NIAID NIH HHS/United States ; //Pfizer/ ; //Veterans Affairs Research Service/ ; R01 AI108479/NH/NIH HHS/United States ; }, mesh = {Humans ; *Streptococcus pneumoniae/isolation &amp; purification/genetics ; Male ; Adult ; Female ; *Pneumococcal Infections/microbiology ; *HIV Infections/complications/microbiology ; *Nasopharynx/microbiology/virology ; *Microbiota ; Middle Aged ; *HIV-1/genetics ; RNA, Ribosomal, 16S/genetics ; Oropharynx/microbiology/virology ; Respiratory Tract Infections/microbiology/virology/epidemiology ; }, abstract = {BACKGROUND: The substantial risk for respiratory and invasive infections with Streptococcus pneumoniae (Spn) among people with HIV-1 (PWH) begins with asymptomatic colonization. The frequency of Spn colonization among US adults with and without HIV-1 infection is not well characterized in the conjugate vaccine era.<br><br>METHODS: We determined Spn colonization frequency by culture and specific lytA gene quantitative polymerase chain reaction (PCR) and microbiota profile by 16S ribosomal RNA gene sequencing in nasopharyngeal (NP) and oropharyngeal (OP) DNA from 138 PWH and 93 control adults and associated clinical characteristics.<br><br>RESULTS: The frequencies of Spn colonization among PWH and controls did not differ (11.6% vs 8.6%, respectively; P = .46) using combined results of culture and PCR, independent of vaccination or behavioral risks. PWH showed altered microbiota composition (ie, &#x3b2;-diversity; NP: P = .0028, OP: P = .0098), decreased &#x3b1;-diversity (NP: P = .024, OP: P = .0045), and differences in the relative abundance of multiple bacterial taxa. Spn colonization was associated with altered &#x3b2;-diversity in the nasopharynx (P = .011) but not oropharynx (P = .21).<br><br>CONCLUSIONS: Despite widespread conjugate vaccine and antiretroviral use, frequencies of Spn colonization among PWH and controls are currently consistent with those reported in the preconjugate era. The persistently increased risk of pneumococcal disease despite antiretroviral therapy may relate to behavioral and immunologic variables other than colonization.}, }
@article {pmid38717446, year = {2024}, author = {Akouris, PP and Stuivenberg, GA and Chmiel, JA and Kiattiburut, W and Poon, A and Reid, G and Burton, JP}, title = {Ethanolamine enhances adhesion, promotes microcompartment formation, and modulates gene expression in Levilactobacillus brevis ATCC 14869.}, journal = {Gut microbes}, volume = {16}, number = {1}, pages = {2350778}, pmid = {38717446}, issn = {1949-0984}, mesh = {*Ethanolamine/metabolism ; *Gene Expression Regulation, Bacterial ; *Bacterial Adhesion/drug effects ; *Levilactobacillus brevis/genetics/metabolism ; Humans ; Bacterial Proteins/genetics/metabolism ; Gastrointestinal Microbiome ; Animals ; Virulence/genetics ; }, abstract = {Ethanolamine is an abundant compound in the gastrointestinal tract and a valuable source of carbon and nitrogen for pathogenic bacteria harboring ethanolamine utilization (eut) genes. Eut-positive pathogens can consume free ethanolamine to outcompete commensal microbes, which often lack eut genes, and establish infection. Ethanolamine can also act as a host recognition signal for eut-positive pathogens to upregulate virulence genes during colonization. Therefore, reducing free ethanolamine titers may represent a novel approach to preventing infection by eut-positive pathogens. Interestingly, the commensal microorganism Levilactobacillus brevis ATCC 14869 was found to encode over 18 eut genes within its genome. This led us to hypothesize that L. brevis can compete with eut-positive pathogens by clearing free ethanolamine from the environment. Our results demonstrate that despite being unable to metabolize ethanolamine under most conditions, L. brevis ATCC 14869 responds to the compound by increasing the expression of genes encoding proteins involved in microcompartment formation and adhesion to the intestinal epithelial barrier. The improved intestinal adhesion of L. brevis in the presence of ethanolamine also enhanced the exclusion of eut-positive pathogens from adhering to intestinal epithelial cells. These findings support further studies to test whether L. brevis ATCC 14869 can counter enteric pathogens and prevent or reduce the severity of infections. Overall, the metabolic capabilities of L. brevis ATCC 14869 offer a unique opportunity to add to the armamentarium of antimicrobial therapies as well as our understanding of the mechanisms used by beneficial microbes to sense and adapt to host microenvironments.}, }
@article {pmid38717124, year = {2024}, author = {Yadegar, A and Bar-Yoseph, H and Monaghan, TM and Pakpour, S and Severino, A and Kuijper, EJ and Smits, WK and Terveer, EM and Neupane, S and Nabavi-Rad, A and Sadeghi, J and Cammarota, G and Ianiro, G and Nap-Hill, E and Leung, D and Wong, K and Kao, D}, title = {Fecal microbiota transplantation: current challenges and future landscapes.}, journal = {Clinical microbiology reviews}, volume = {37}, number = {2}, pages = {e0006022}, pmid = {38717124}, issn = {1098-6618}, support = {PJT168954//Canadian Government | Canadian Institutes of Health Research (CIHR)/ ; //NIHR | NIHR Nottingham Biomedical Research Centre (BRC)/ ; }, mesh = {*Fecal Microbiota Transplantation/methods ; Humans ; *Gastrointestinal Microbiome ; Clostridium Infections/therapy/microbiology ; Inflammatory Bowel Diseases/therapy/microbiology ; Animals ; }, abstract = {SUMMARYGiven the importance of gut microbial homeostasis in maintaining health, there has been considerable interest in developing innovative therapeutic strategies for restoring gut microbiota. One such approach, fecal microbiota transplantation (FMT), is the main "whole gut microbiome replacement" strategy and has been integrated into clinical practice guidelines for treating recurrent Clostridioides difficile infection (rCDI). Furthermore, the potential application of FMT in other indications such as inflammatory bowel disease (IBD), metabolic syndrome, and solid tumor malignancies is an area of intense interest and active research. However, the complex and variable nature of FMT makes it challenging to address its precise functionality and to assess clinical efficacy and safety in different disease contexts. In this review, we outline clinical applications, efficacy, durability, and safety of FMT and provide a comprehensive assessment of its procedural and administration aspects. The clinical applications of FMT in children and cancer immunotherapy are also described. We focus on data from human studies in IBD in contrast with rCDI to delineate the putative mechanisms of this treatment in IBD as a model, including colonization resistance and functional restoration through bacterial engraftment, modulating effects of virome/phageome, gut metabolome and host interactions, and immunoregulatory actions of FMT. Furthermore, we comprehensively review omics technologies, metagenomic approaches, and bioinformatics pipelines to characterize complex microbial communities and discuss their limitations. FMT regulatory challenges, ethical considerations, and pharmacomicrobiomics are also highlighted to shed light on future development of tailored microbiome-based therapeutics.}, }
@article {pmid38711478, year = {2024}, author = {Ramkumar, D and Marty, A and Ramkumar, J and Rosencranz, H and Vedantham, R and Goldman, M and Meyer, E and Steinmetz, J and Weckle, A and Bloedorn, K and Rosier, C}, title = {Food for thought: Making the case for food produced via regenerative agriculture in the battle against non-communicable chronic diseases (NCDs).}, journal = {One health (Amsterdam, Netherlands)}, volume = {18}, number = {}, pages = {100734}, pmid = {38711478}, issn = {2352-7714}, abstract = {Non-communicable diseases (NCDs) pose a global health challenge, leading to substantial morbidity, mortality, and economic strain. Our review underscores the escalating incidence of NCDs worldwide and highlights the potential of regenerative agriculture (RA) products in mitigating these diseases. We also explore the efficacy of dietary interventions in NCD management and prevention, emphasizing the superiority of plant-based diets over those high in processed foods and red meat. Examining the role of the gut microbiome in various diseases, including liver disorders, allergies, metabolic syndrome, inflammatory bowel disease, and colon cancer, we find compelling evidence implicating its influence on disease development. Notably, dietary modifications can positively affect the gut microbiome, fostering a symbiotic relationship with the host and making this a critical strategy in disease prevention and treatment. Investigating agricultural practices, we identify parallels between soil/plant and human microbiome studies, suggesting a crucial link between soil health, plant- and animal-derived food quality, and human well-being. Conventional/Industrial agriculture (IA) practices, characterized in part by use of chemical inputs, have adverse effects on soil microbiome diversity, food quality, and ecosystems. In contrast, RA prioritizes soil health through natural processes, and includes avoiding synthetic inputs, crop rotation, and integrating livestock. Emerging evidence suggests that food from RA systems surpasses IA-produced food in quality and nutritional value. Recognizing the interconnection between human, plant, and soil microbiomes, promoting RA-produced foods emerges as a strategy to improve human health and environmental sustainability. By mitigating climate change impacts through carbon sequestration and water cycling, RA offers dual benefits for human and planetary health and well-being. Emphasizing the pivotal role of diet and agricultural practices in combating NCDs and addressing environmental concerns, the adoption of regional RA systems becomes imperative. Increasing RA integration into local food systems can enhance food quality, availability, and affordability while safeguarding human health and the planet's future.}, }
@article {pmid38710286, year = {2024}, author = {Zhao, F and Wang, J}, title = {Another piece of puzzle for the human microbiome: the gut virome under dietary modulation.}, journal = {Journal of genetics and genomics = Yi chuan xue bao}, volume = {51}, number = {10}, pages = {983-996}, doi = {10.1016/j.jgg.2024.04.013}, pmid = {38710286}, issn = {1673-8527}, mesh = {Humans ; *Gastrointestinal Microbiome ; *Virome/genetics ; *Diet ; Bacteriophages/genetics/physiology ; Bacteria/genetics/classification/virology ; Gene Transfer, Horizontal ; Viruses/genetics ; }, abstract = {The virome is the most abundant and highly variable microbial consortium in the gut. Because of difficulties in isolating and culturing gut viruses and the lack of reference genomes, the virome has remained a relatively elusive aspect of the human microbiome. In recent years, studies on the virome have accumulated growing evidence showing that the virome is diet-modulated and widely involved in regulating health. Here, we review the responses of the gut virome to dietary intake and the potential health implications, presenting changes in the gut viral community and preferences of viral members to particular diets. We further discuss how viral-bacterial interactions and phage lifestyle shifts shape the gut microbiota. We also discuss the specific functions conferred by diet on the gut virome and bacterial community in the context of horizontal gene transfer, as well as the import of new viral members along with the diet. Collating these studies will expand our understanding of the dietary regulation of the gut virome and inspire dietary interventions and health maintenance strategies targeting the gut microbiota.}, }
@article {pmid38709058, year = {2024}, author = {Geaman, W and Choi, BI and Kaindl, J and Gonzalez, C and Wolfe, AJ}, title = {Microbroth dilution method for antibiotic susceptibility testing of fastidious and anaerobic bacteria of the urinary microbiome.}, journal = {Microbiology spectrum}, volume = {12}, number = {6}, pages = {e0031424}, pmid = {38709058}, issn = {2165-0497}, support = {//Pathnostics/ ; }, mesh = {Humans ; *Microbial Sensitivity Tests/methods ; *Anti-Bacterial Agents/pharmacology ; *Microbiota/drug effects ; *Bacteria, Anaerobic/drug effects/isolation &amp; purification ; Urine/microbiology ; Urinary Tract Infections/microbiology ; Bacteria/drug effects/isolation &amp; purification/growth &amp; development ; Culture Media/chemistry ; }, abstract = {UNLABELLED: Bacterial isolates from the human urinary microbiome have been extensively studied for their antibiotic resistance; however, little work has been done on those isolates that are difficult to grow in vitro. This study was designed to qualify a serum-based medium, New York City Broth III (NYCIII), and a broth microdilution method to determine the antibiotic susceptibility of previously underreported or undescribed microbes that have a difficult time growing in standard Mueller-Hinton broth. Here, we demonstrate that NYCIII microbroth dilution can be an effective method for the determination of antibiotic susceptibility of species found in the human urinary microbiome. We show that this method serves well to characterize fastidious and anaerobic urinary microbes that have no Clinical and Laboratory Standards Institute (CLSI) guidelines, including several in the families Aerococcaceae, Lactobacillaceae, or Actinomycetaceae. Previous studies using expanded quantitative urine culture reveal that urine samples from clinical patients are commonly polymicrobial in composition. Thus, we test whether NYCIII can serve as a viable harmonized medium, capable of supporting antibiotic susceptibility testing in a range of fastidious, non-fastidious, and anaerobic urinary microbes. We propose this methodology to be standardized comparable to CLSI standards to allow for resistance testing in uncharacterized urinary bacteria.<br><br>IMPORTANCE: Antibiotic susceptibilities of fastidious and anaerobic bacteria of the human urinary microbiome are largely underreported due to difficulty in growing them in the lab environment. The current standard medium, Muller-Hinton broth, has difficulty supporting the growth of many of these species, leaving microbiologists without a standardized method. To address this need, this study offers a methodology to survey susceptibilities in a high-throughput manner of these understudied microbes with a proposed harmonized medium, NYCIII, which is capable of supporting the growth of both fastidious and non-fastidious urinary microbes. Broader standardization of this method can allow for the development of antibiotic-resistant breakpoints of the many uncharacterized urinary microbes.}, }
@article {pmid38707185, year = {2024}, author = {Koudokpon, H and Legba, BB and Dougnon, V and Mero, S and Bankole, H and Haukka, K}, title = {Strengthening clinical bacteriology laboratory diagnostics to combat sepsis and antimicrobial resistance in Benin: a train-the-trainer approach.}, journal = {Frontiers in medicine}, volume = {11}, number = {}, pages = {1281418}, pmid = {38707185}, issn = {2296-858X}, abstract = {INTRODUCTION: Improved laboratory diagnostics is needed to support sepsis diagnosis and combat increasing antibiotic resistance in Benin. We trained clinical laboratory experts and technicians to improve their skills in accurate and up-to-date diagnostics.<br><br>METHODS: A Train-the-Trainer (TtT) approach was used to design the course that combines theoretical and practical laboratory skills, specifically addressing the knowledge gaps we had previously identified in our national survey. Pedagogical methods were student-centered, including peer learning, use of online materials, practical laboratory work and pre-and post-course tests.<br><br>RESULTS: We first trained 10 trainers who in turn trained 40 laboratory technicians from across the country, from both public and private clinical and veterinary laboratories. The trainers also prepared standard operation procedures for blood culture and antibiotic susceptibility testing based on international standards. Three months after the training, follow-up visits were made to the laboratories where the implementation of the new skills was evaluated. The progress of the participants observed during the course and the implementation of the new skills afterwards proved the training to be effective.<br><br>DISCUSSION: The professional networks created during the training, the empowerment that utilizes local knowledge resources, and the government support for our initiative can be expected to bring sustainability to the initiative and support the participation of Beninese laboratories in international surveillance programs in the future.}, }
@article {pmid38706561, year = {2024}, author = {Alagiakrishnan, K and Morgadinho, J and Halverson, T}, title = {Approach to the diagnosis and management of dysbiosis.}, journal = {Frontiers in nutrition}, volume = {11}, number = {}, pages = {1330903}, pmid = {38706561}, issn = {2296-861X}, abstract = {All microorganisms like bacteria, viruses and fungi that reside within a host environment are considered a microbiome. The number of bacteria almost equal that of human cells, however, the genome of these bacteria may be almost 100 times larger than the human genome. Every aspect of the physiology and health can be influenced by the microbiome living in various parts of our body. Any imbalance in the microbiome composition or function is seen as dysbiosis. Different types of dysbiosis are seen and the corresponding symptoms depend on the site of microbial imbalance. The contribution of the intestinal and extra-intestinal microbiota to influence systemic activities is through interplay between different axes. Whole body dysbiosis is a complex process involving gut microbiome and non-gut related microbiome. It is still at the stage of infancy and has not yet been fully understood. Dysbiosis can be influenced by genetic factors, lifestyle habits, diet including ultra-processed foods and food additives, as well as medications. Dysbiosis has been associated with many systemic diseases and cannot be diagnosed through standard blood tests or investigations. Microbiota derived metabolites can be analyzed and can be useful in the management of dysbiosis. Whole body dysbiosis can be addressed by altering lifestyle factors, proper diet and microbial modulation. The effect of these interventions in humans depends on the beneficial microbiome alteration mostly based on animal studies with evolving evidence from human studies. There is tremendous potential for the human microbiome in the diagnosis, treatment, and prognosis of diseases, as well as, for the monitoring of health and disease in humans. Whole body system-based approach to the diagnosis of dysbiosis is better than a pure taxonomic approach. Whole body dysbiosis could be a new therapeutic target in the management of various health conditions.}, }
@article {pmid38702623, year = {2024}, author = {Shen, S and Liu, X and Huang, J and Sun, Y and Liu, B and Song, W and Meng, L and Du, M and Feng, Q}, title = {Efficacy of a mouthwash containing ε-poly-L-lysine, funme peptides and domiphen in reducing halitosis and supragingival plaque: a randomized clinical trial.}, journal = {BMC oral health}, volume = {24}, number = {1}, pages = {525}, pmid = {38702623}, issn = {1472-6831}, support = {2021SFGC0502//the "Tang Scholar" Program, Major Innovation Projects in Shandong Province/ ; ZR2022QH278//Natural Science Foundation of Shandong Province/ ; tsqn202306369//Construction Engineering Special Fund of "Taishan Scholars" of Shandong Province/ ; ZR2021JQ29//Excellent Young Scientist Foundation of Shandong Province/ ; 2019//Taishan Young Scientist Project of Shandong Province/ ; 2021GXRC021//Periodontitis innovation team of Jinan City/ ; 2021SFGC0502//Major Innovation Projects in Shandong Province/ ; 2020KJK001//Oral Microbiome Innovation Team of Shandong Province/ ; 2021ZDSYS18//Key Technology Research and Development Program of Shandong Province/ ; 2021SFGC0502//Shandong Province Major Scientifc and Technical Innovation Project/ ; }, mesh = {Humans ; *Halitosis/prevention &amp; control/drug therapy/microbiology ; *Mouthwashes/therapeutic use ; *Dental Plaque/microbiology/prevention &amp; control ; Double-Blind Method ; Male ; Female ; *Polylysine/therapeutic use ; Adult ; Microbial Sensitivity Tests ; Young Adult ; Anti-Bacterial Agents/therapeutic use/pharmacology ; Porphyromonas gingivalis/drug effects ; Fusobacterium nucleatum/drug effects ; Fibroblasts/drug effects ; Peptides/therapeutic use/pharmacology ; Aggregatibacter actinomycetemcomitans/drug effects ; Streptococcus mutans/drug effects ; }, abstract = {OBJECTIVE: To evaluate the antibacterial effectiveness of a combination of ε-poly-L-lysine (ε-PL), funme peptide (FP) as well as domiphen against oral pathogens, and assess the efficacy of a BOP® mouthwash supplemented with this combination in reducing halitosis and supragingival plaque in a clinical trial.<br><br>MATERIALS AND METHODS: The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of the compound against Fusobacterium nucleatum, Porphyromonas gingivalis, Streptococcus mutans, and Aggregatibacter actinomycetemcomitans were determined by the gradient dilution method. Subsequently, the CCK-8 assay was used to detect the toxicity of mouthwash on human gingival fibroblastst, and the effectiveness in reducing halitosis and supragingival plaque of the mouthwash supplemented with the combination was analyzed by a randomized, double-blind, parallel-controlled clinical trial.<br><br>RESULTS: The combination exhibited significant inhibitory effects on tested oral pathogens with the MIC&#x2009;<&#x2009;1.56% (v/v) and the MBC&#x2009;<&#x2009;3.13% (v/v), and the mouthwash containing this combination did not inhibit the viability of human gingival fibroblasts at the test concentrations. The clinical trial showed that the test group displayed notably lower volatile sulfur compounds (VSCs) at 0, 10, 24&#xa0;h, and 7 d post-mouthwash (P&#x2009;<&#x2009;0.05), compared with the baseline. After 7 days, the VSC levels of the and control groups were reduced by 50.27% and 32.12%, respectively, and notably cutting severe halitosis by 57.03% in the test group. Additionally, the Plaque Index (PLI) of the test and control group decreased by 54.55% and 8.38%, respectively, and there was a significant difference in PLI between the two groups after 7 days (P&#x2009;<&#x2009;0.01).<br><br>CONCLUSIONS: The combination of &#x3b5;-PL, FP and domiphen demonstrated potent inhibitory and bactericidal effects against the tested oral pathogens, and the newly formulated mouthwash added with the combination exhibited anti-dental plaque and anti-halitosis properties in a clinical trial and was safe.<br><br>TRIAL REGISTRATION: The randomized controlled clinical trial was registered on Chinese Clinical Trial Registry (No. ChiCTR2300073816, Date: 21/07/2023).}, }
@article {pmid38700829, year = {2024}, author = {Jang, CS and Kim, H and Kim, D and Han, B}, title = {MicroPredict: predicting species-level taxonomic abundance of whole-shotgun metagenomic data using only 16S amplicon sequencing data.}, journal = {Genes &amp; genomics}, volume = {46}, number = {6}, pages = {701-712}, pmid = {38700829}, issn = {2092-9293}, mesh = {*RNA, Ribosomal, 16S/genetics ; *Metagenomics/methods ; Humans ; *Microbiota/genetics ; Machine Learning ; Whole Genome Sequencing/methods ; Metagenome/genetics ; Bacteria/genetics/classification ; }, abstract = {BACKGROUND: The importance of the human microbiome in the analysis of various diseases is emerging. The two main methods used to profile the human microbiome are 16S rRNA gene sequencing (16S sequencing) and whole-genome shotgun sequencing (WGS). Owing to the full coverage of the genome in sequencing, WGS has multiple advantages over 16S sequencing, including higher taxonomic profiling resolution at the species-level and functional profiling analysis. However, 16S sequencing remains widely used because of its relatively low cost. Although WGS is the standard method for obtaining accurate species-level data, we found that 16S sequencing data contained rich information to predict high-resolution species-level abundances with reasonable accuracy.<br><br>OBJECTIVE: In this study, we proposed MicroPredict, a method for accurately predicting WGS-comparable species-level abundance data using 16S taxonomic profile data.<br><br>METHODS: We employed a mixed model using two key strategies: (1) modeling both sample- and species-specific information for predicting WGS abundances, and (2) accounting for the possible correlations among different species.<br><br>RESULTS: We found that MicroPredict outperformed the other machine learning methods.<br><br>CONCLUSION: We expect that our approach will help researchers accurately approximate the species-level abundances of microbiome profiles in datasets for which only cost-effective 16S sequencing has been applied.}, }
@article {pmid38697697, year = {2024}, author = {Araujo, R and Merino-Ribas, A and Pereira, L and Campos, J and Silva, N and Alencastre, IS and Pestana, M and Sampaio-Maia, B}, title = {The urogenital microbiome in chronic kidney disease patients on peritoneal dialysis.}, journal = {Nefrologia}, volume = {44}, number = {2}, pages = {194-203}, doi = {10.1016/j.nefroe.2024.04.004}, pmid = {38697697}, issn = {2013-2514}, mesh = {Humans ; Female ; Male ; *Peritoneal Dialysis/adverse effects ; Middle Aged ; *Microbiota ; *Renal Insufficiency, Chronic/microbiology/therapy/complications ; Aged ; Urogenital System/microbiology ; Adult ; Feces/microbiology ; }, abstract = {INTRODUCTION AND OBJECTIVES: Diabetes, dyslipidemia, older age, gender, urinary tract infections, and recent antibiotic intake have been associated with a decrease in the urobiome richness and other fluctuations in this microbiome. Gut and blood microbiome have been reported to be altered in patients with chronic kidney disease (CKD), and specifically in peritoneal dialysis (PD) patients. Still, there are currently no studies describing the urogenital microbiome in CKD-PD patients. In this study we characterized the urobiome profile in 46 PD patients and analyzed its clinical and inflammatory parameters.<br><br>MATERIALS AND METHODS: Mid-stream urine, fecal and blood samples were collected from 46 patients undergoing PD at Centro Hospitalar Universit&#xe1;rio de S&#xe3;o Jo&#xe3;o (CHUSJ) in Porto, Portugal. Exclusion criteria were age under 18 years old, inability to give informed consent, history of infection in the last three months, and antibiotic intake in the last three months. The microbiome communities were analyzed by amplification and sequencing of the V3-V4 region of the bacterial 16S rRNA gene. Correlations with the patients' clinical data and inflammatory profile were performed.<br><br>RESULTS: CKD-PD patients presented a unique urobiome profile dominated by Bacillota, Actinomycetota and Pseudomonadota and characterized by a lower Shannon diversity than fecal and blood microbiome. The taxonomic profiles of urogenital samples were organized in multiple subtypes dominated by populations of Lactobacillus, Staphylococcus, Streptococcus, Gardnerella, Prevotella, Escherichia-Shigella, being similar to other non-PD-CKD patients. Gender, sCD14, residual diuresis and history of peritonitis were significantly associated to variations in the urobiome. Although not reaching statistical significance, diabetes and the time on PD also showed association with particular taxonomic groups. Depletion of Gardnerella, Staphylococcus, Corynebacterium, Lactobacillus or Dermabacter populations correlated with CKD-PD patients with history of diabetes, history of peritonitis and altered levels of sCD14.<br><br>CONCLUSIONS: Our results highlight urogenital microbiome as a potential partner and/or marker in the overall health state of CKD-PD patients.}, }
@article {pmid38695302, year = {2024}, author = {Roussel, C and Sola, M and Lessard-Lord, J and Nallabelli, N and Généreux, P and Cavestri, C and Azeggouar Wallen, O and Villano, R and Raymond, F and Flamand, N and Silvestri, C and Di Marzo, V}, title = {Human gut microbiota and their production of endocannabinoid-like mediators are directly affected by a dietary oil.}, journal = {Gut microbes}, volume = {16}, number = {1}, pages = {2335879}, pmid = {38695302}, issn = {1949-0984}, mesh = {Humans ; *Gastrointestinal Microbiome/drug effects ; *Bacteria/classification/metabolism/isolation &amp; purification/genetics ; *Endocannabinoids/metabolism ; Colon/microbiology/metabolism ; Ileum/microbiology/metabolism ; Fatty Acids, Omega-3/metabolism ; Plant Oils/metabolism/pharmacology ; Dietary Supplements ; Adult ; Male ; }, abstract = {Dietary omega-3 polyunsaturated fatty acids (n-3 PUFAs) and the gut microbiome affect each other. We investigated the impact of supplementation with Buglossoides arvensis oil (BO), rich in stearidonic acid (SDA), on the human gut microbiome. Employing the Mucosal Simulator of the Human Intestinal Microbial Ecosystem (M-SHIME), we simulated the ileal and ascending colon microbiomes of four donors. Our results reveal two distinct microbiota clusters influenced by BO, exhibiting shared and contrasting shifts. Notably, Bacteroides and Clostridia abundance underwent similar changes in both clusters, accompanied by increased propionate production in the colon. However, in the ileum, cluster 2 displayed a higher metabolic activity in terms of BO-induced propionate levels. Accordingly, a triad of bacterial members involved in propionate production through the succinate pathway, namely Bacteroides, Parabacteroides, and Phascolarctobacterium, was identified particularly in this cluster, which also showed a surge of second-generation probiotics, such as Akkermansia, in the colon. Finally, we describe for the first time the capability of gut bacteria to produce N-acyl-ethanolamines, and particularly the SDA-derived N-stearidonoyl-ethanolamine, following BO supplementation, which also stimulated the production of another bioactive endocannabinoid-like molecule, commendamide, in both cases with variations across individuals. Spearman correlations enabled the identification of bacterial genera potentially involved in endocannabinoid-like molecule production, such as, in agreement with previous reports, Bacteroides in the case of commendamide. This study suggests that the potential health benefits on the human microbiome of certain dietary oils may be amenable to stratified nutrition strategies and extend beyond n-3 PUFAs to include microbiota-derived endocannabinoid-like mediators.}, }
@article {pmid38694799, year = {2024}, author = {Zhang, Y and Xue, G and Wang, F and Zhang, J and Xu, L and Yu, C}, title = {The impact of antibiotic exposure on antibiotic resistance gene dynamics in the gut microbiota of inflammatory bowel disease patients.}, journal = {Frontiers in microbiology}, volume = {15}, number = {}, pages = {1382332}, pmid = {38694799}, issn = {1664-302X}, abstract = {BACKGROUND: While antibiotics are commonly used to treat inflammatory bowel disease (IBD), their widespread application can disturb the gut microbiota and foster the emergence and spread of antibiotic resistance. However, the dynamic changes to the human gut microbiota and direction of resistance gene transmission under antibiotic effects have not been clearly elucidated.<br><br>METHODS: Based on the Human Microbiome Project, a total of 90 fecal samples were collected from 30 IBD patients before, during and after antibiotic treatment. Through the analysis workflow of metagenomics, we described the dynamic process of changes in bacterial communities and resistance genes pre-treatment, during and post-treatment. We explored potential consistent relationships between gut microbiota and resistance genes, and established gene transmission networks among species before and after antibiotic use.<br><br>RESULTS: Exposure to antibiotics can induce alterations in the composition of the gut microbiota in IBD patients, particularly a reduction in probiotics, which gradually recovers to a new steady state after cessation of antibiotics. Network analyses revealed intra-phylum transfers of resistance genes, predominantly between taxonomically close organisms. Specific resistance genes showed increased prevalence and inter-species mobility after antibiotic cessation.<br><br>CONCLUSION: This study demonstrates that antibiotics shape the gut resistome through selective enrichment and promotion of horizontal gene transfer. The findings provide insights into ecological processes governing resistance gene dynamics and dissemination upon antibiotic perturbation of the microbiota. Optimizing antibiotic usage may help limit unintended consequences like increased resistance in gut bacteria during IBD management.}, }
@article {pmid38690563, year = {2024}, author = {Karaman, I and Pathak, A and Bayik, D and Watson, DC}, title = {Harnessing Bacterial Extracellular Vesicle Immune Effects for Cancer Therapy.}, journal = {Pathogens &amp; immunity}, volume = {9}, number = {1}, pages = {56-90}, pmid = {38690563}, issn = {2469-2964}, support = {K99 CA277242/CA/NCI NIH HHS/United States ; }, abstract = {There are a growing number of studies linking the composition of the human microbiome to disease states and treatment responses, especially in the context of cancer. This has raised significant interest in developing microbes and microbial products as cancer immunotherapeutics that mimic or recapitulate the beneficial effects of host-microbe interactions. Bacterial extracellular vesicles (bEVs) are nano-sized, membrane-bound particles secreted by essentially all bacteria species and contain a diverse bioactive cargo of the producing cell. They have a fundamental role in facilitating interactions among cells of the same species, different microbial species, and even with multicellular host organisms in the context of colonization (microbiome) and infection. The interaction of bEVs with the immune system has been studied extensively in the context of infection and suggests that bEV effects depend largely on the producing species. They thus provide functional diversity, while also being nonreplicative, having inherent cell-targeting qualities, and potentially overcoming natural barriers. These characteristics make them highly appealing for development as cancer immunotherapeutics. Both natively secreted and engineered bEVs are now being investigated for their application as immunotherapeutics, vaccines, drug delivery vehicles, and combinations of the above, with promising early results. This suggests that both the intrinsic immunomodulatory properties of bEVs and their ability to be modified could be harnessed for the development of next-generation microbe-inspired therapies. Nonetheless, there remain major outstanding questions regarding how the observed preclinical effectiveness will translate from murine models to primates, and humans in particular. Moreover, research into the pharmacology, toxicology, and mass manufacturing of this potential novel therapeutic platform is still at early stages. In this review, we highlight the breadth of bEV interactions with host cells, focusing on immunologic effects as the main mechanism of action of bEVs currently in preclinical development. We review the literature on ongoing efforts to develop natively secreted and engineered bEVs from a variety of bacterial species for cancer therapy and finally discuss efforts to overcome outstanding challenges that remain for clinical translation.}, }
@article {pmid38688858, year = {2024}, author = {Sminia, TJ and Aalvink, S and de Jong, H and Tempelaars, MH and Zuilhof, H and Abee, T and de Vos, WM and Tytgat, HLP and Wennekes, T}, title = {Probing Peptidoglycan Synthesis in the Gut Commensal Akkermansia Muciniphila with Bioorthogonal Chemical Reporters.}, journal = {Chembiochem : a European journal of chemical biology}, volume = {25}, number = {19}, pages = {e202400037}, doi = {10.1002/cbic.202400037}, pmid = {38688858}, issn = {1439-7633}, support = {//Netherlands Foundation for Scientific Research (NWO)/ ; 722.011.006//VENI/ ; 723.014.005//VIDI/ ; //Laboratory of Microbiology/ ; //Soehngen Institute of Anaerobic Microbiology/ ; //SIAM/ ; 024.002.002//NWO/ ; //NWO/ ; //WMdV/ ; //Laboratory of Biochemistry, Wageningen University/ ; }, mesh = {*Peptidoglycan/metabolism/chemistry/biosynthesis ; *Akkermansia/metabolism ; *Gastrointestinal Microbiome ; Humans ; Molecular Probes/chemistry/metabolism ; Click Chemistry ; Cyclopropanes/chemistry/metabolism ; }, abstract = {Our gut microbiota directly influences human physiology in health and disease. The myriad of surface glycoconjugates in both the bacterial cell envelope and our gut cells dominate the microbiota-host interface and play a critical role in host response and microbiota homeostasis. Among these, peptidoglycan is the basic glycan polymer offering the cell rigidity and a basis on which many other glycoconjugates are anchored. To directly study peptidoglycan in gut commensals and obtain the molecular insight required to understand their functional activities we need effective techniques like chemical probes to label peptidoglycan in live bacteria. Here we report a chemically guided approach to study peptidoglycan in a key mucin-degrading gut microbiota member of the Verrucomicrobia phylum, Akkermansia muciniphila. Two novel non-toxic tetrazine click-compatible peptidoglycan probes with either a cyclopropene or isonitrile handle allowed for the detection and imaging of peptidoglycan synthesis in this intestinal species.}, }
@article {pmid38687072, year = {2024}, author = {Nagpal, S and Mande, SS and Hooda, H and Dutta, U and Taneja, B}, title = {EnsembleSeq: a workflow towards real-time, rapid, and simultaneous multi-kingdom-amplicon sequencing for holistic and resource-effective microbiome research at scale.}, journal = {Microbiology spectrum}, volume = {12}, number = {6}, pages = {e0415023}, pmid = {38687072}, issn = {2165-0497}, support = {OLP2306//CSIR-Institute of Genomics and Integrative Biology/ ; }, mesh = {Humans ; *RNA, Ribosomal, 16S/genetics ; *Microbiota/genetics ; *Bacteria/genetics/classification/isolation &amp; purification ; *Saliva/microbiology ; *Fungi/genetics/classification/isolation &amp; purification ; Workflow ; DNA, Bacterial/genetics ; High-Throughput Nucleotide Sequencing/methods ; Sequence Analysis, DNA/methods ; DNA, Fungal/genetics ; }, abstract = {UNLABELLED: Bacterial communities are often concomitantly present with numerous microorganisms in the human body and other natural environments. Amplicon-based microbiome studies have generally paid skewed attention, that too at a rather shallow genus level resolution, to the highly abundant bacteriome, with interest now forking toward the other microorganisms, particularly fungi. Given the generally sparse abundance of other microbes in the total microbiome, simultaneous sequencing of amplicons targeting multiple microbial kingdoms could be possible even with full multiplexing. Guiding studies are currently needed for performing and monitoring multi-kingdom-amplicon sequencing and data capture at scale. Aiming to address these gaps, amplification of full-length bacterial 16S rRNA gene and entire fungal internal-transcribed spacer (ITS) region was performed for human saliva samples (n = 96, including negative and positive controls). Combined amplicon DNA libraries were prepared for nanopore sequencing using a major fraction of 16S molecules and a minor fraction of ITS amplicons. Sequencing was performed in a single run of an R10.4.1 flow cell employing the latest V14 chemistry. An approach for real-time monitoring of the species saturation using dynamic rarefaction was designed as a guiding determinant of optimal run time. Real-time saturation monitoring for both bacterial and fungal species enabled the completion of sequencing within 30 hours, utilizing less than 60% of the total nanopores. Approximately 5 million high quality (HQ) taxonomically assigned reads were generated (~4.2 million bacterial and 0.7 million fungal), providing a wider (beyond bacteriome) snapshot of human oral microbiota at species-level resolution. Among the more than 400 bacterial and 240 fungal species identified in the studied samples, the species of Streptococcus (e.g., Streptococcus mitis and Streptococcus oralis) and Candida (e.g., Candida albicans and Candida tropicalis) were observed to be the dominating microbes in the oral cavity, respectively. This conformed well with the previous reports of the human oral microbiota. EnsembleSeq provides a proof-of-concept toward the identification of both fungal and bacterial species simultaneously in a single fully multiplexed nanopore sequencing run in a time- and resource-effective manner. Details of this workflow, along with the associated codebase, are provided to enable large-scale application for a holistic species-level microbiome study.<br><br>IMPORTANCE: Human microbiome is a sum total of a variety of microbial genomes (including bacteria, fungi, protists, viruses, etc.) present in and on the human body. Yet, a majority of amplicon-based microbiome studies have largely remained skewed toward bacteriome as an assumed proxy of the total microbiome, primarily at a shallow genus level. Cost, time, effort, data quality/management, and importantly lack of guiding studies often limit progress in the direction of moving beyond bacteriome. Here, EnsembleSeq presents a proof-of-concept toward concomitantly capturing multiple-kingdoms of microorganisms (bacteriome and mycobiome) in a fully multiplexed (96-sample) single run of long-read amplicon sequencing. In addition, the workflow captures dynamic tracking of species-level saturation in a time- and resource-effective manner.}, }
@article {pmid38687061, year = {2024}, author = {Kallio, S and Jian, C and Korpela, K and Kukkonen, AK and Salonen, A and Savilahti, E and Kuitunen, M and M de Vos, W}, title = {Early-life gut microbiota associates with allergic rhinitis during 13-year follow-up in a Finnish probiotic intervention cohort.}, journal = {Microbiology spectrum}, volume = {12}, number = {6}, pages = {e0413523}, pmid = {38687061}, issn = {2165-0497}, support = {308253//Research Council of Finland (AKA)/ ; }, mesh = {Humans ; *Gastrointestinal Microbiome ; *Probiotics/administration &amp; dosage ; *Rhinitis, Allergic/microbiology ; Female ; Finland/epidemiology ; Adolescent ; Child, Preschool ; Male ; Infant ; Child ; Follow-Up Studies ; *Feces/microbiology ; RNA, Ribosomal, 16S/genetics ; Pregnancy ; Infant, Newborn ; Cohort Studies ; Bacteria/classification/genetics/isolation &amp; purification ; }, abstract = {Perinatal and early-life factors reported to affect risk of allergic diseases may be mediated by changes in the gut microbiota. Here, we explored the associations between the infant gut microbiota and allergic morbidity in childhood until 13 years of age in a subgroup of the FLORA probiotic intervention cohort. A mixture of four probiotic strains with galacto-oligosaccharides was administrated to the mothers from the 36th week of the pregnancy and later to their infants until 6 months of age. The infants were monitored for the manifestations of atopic eczema, food allergy, allergic rhinitis, and asthma by a pediatrician at 2 and 5 years of age; the allergic status was subsequently verified by a questionnaire at 10 and 13 years of age. The fecal microbiota at 3 months was profiled by 16S rRNA amplicon sequencing targeting the V3-V4 region, with and without adjusting for potentially important early-life factors. Overall, the positive diagnosis for allergic rhinitis between 2 and 13 years was associated with microbiota composition both in non-adjusted and adjusted models. This association was more pronounced in children born to one parent with confirmed atopic diseases compared to those who had two atopic parents and was characterized by a lower relative abundance of Bifidobacterium and Escherichia/Shigella spp. and a higher proportion of Bacteroides. While the probiotic and galacto-oligosaccharides intervention in the entire cohort was previously shown to reduce the prevalence of eczema to a certain extent, no associations were found between the 3-month gut microbiota and childhood eczema in the studied sub-cohort.IMPORTANCEAllergic diseases have increased in prevalence during the past decades globally. Although probiotics have been considered a promising strategy for preventing certain allergy related symptoms, studies connecting the infant gut microbiota and later life allergic morbidity in various populations remain limited. The present study supports an association between the infant microbiota and allergic morbidity after first years of life, which has been rarely examined.CLINICAL TRIALSRegistered at ClinicalTrials.gov (NCT00298337).}, }
@article {pmid38686448, year = {2024}, author = {Zhang, Y and Miao, D and Su, M and Tang, Y and Zhou, M and Yu, Y and Guo, X and Wu, D}, title = {Synergistic Drug-Loaded Shear-Thinning Star Polymer Hydrogel Facilitates Gastrointestinal Lesion Resection and Promotes Wound Healing.}, journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)}, volume = {11}, number = {26}, pages = {e2309586}, pmid = {38686448}, issn = {2198-3844}, support = {2023B0303000025//Guangdong Major Project of Basic and Applied Basic Research/ ; 51925308//National Natural Science Foundation of China/ ; 2022YFA1304000//National Key Research and Development Program of China/ ; SL2023B03J00112//Science and Technology Program of Guangzhou/ ; KY012021209//GDPH Supporting Fund for Talent Program/ ; KY0120240026//GDPH Supporting Fund for Talent Program/ ; 2024A1515011636//Guangdong Basic and Applied Basic Research Foundation/ ; 23yxqntd002//Fundamental Research Funds for the Central Universities, Sun Yat-sen University/ ; //Guangdong Basic Research Center of Excellence for Functional Molecular Engineering/ ; }, mesh = {Animals ; *Wound Healing/drug effects ; Swine ; *Hydrogels/chemistry ; *Polymers/chemistry ; Polyethylene Glycols/chemistry ; Disease Models, Animal ; Methacrylates/chemistry ; Anti-Bacterial Agents/pharmacology/administration &amp; dosage ; }, abstract = {Easy injection, long-lasting barrier, and drug loading are the critical properties of submucosal injection materials for endoscopic surgery. However, conventional injectable polymers face challenges in simultaneously attaining these properties due to the inherent conflict between injectability and in situ stability. Here, a multi-arm star polymer hydrogel (denoted as βCP hydrogel) with long-lasting submucosal barrier (exceeding 120 min), rapid hemostasis, and sustained antibacterial properties is successfully developed by grafting poly(oligo(ethylene glycol) methyl ether methacrylate) (PEGMA) side-chains from β-CD via atom transfer radical polymerization (ATRP). During the onset of shearing, βCP hydrogel experiences the unwinding of polymer side-chains between neighboring star polymers, which facilitates the process of endoscopic injectability. After submucosal injection, βCP hydrogel undergoes the winding of polymer side-chains, thereby establishing a long-lasting barrier cushion. Meanwhile, owing to its distinctive structures with a hydrophobic inner cavity and an outer layer of hydrophilic polymer side-chains, βCP hydrogel enables simultaneous loading and on-demand release of diverse categories of drugs. This unique performance can adapt to the diverse demands during different stages of wound healing in a porcine endoscopic surgery model. These results indicate an appealing prospect for new application of star polymers as a good submucosal injection material in endoscopic treatments.}, }
@article {pmid38680911, year = {2024}, author = {Chen See, JR and Leister, J and Wright, JR and Kruse, PI and Khedekar, MV and Besch, CE and Kumamoto, CA and Madden, GR and Stewart, DB and Lamendella, R}, title = {Clostridioides difficile infection is associated with differences in transcriptionally active microbial communities.}, journal = {Frontiers in microbiology}, volume = {15}, number = {}, pages = {1398018}, pmid = {38680911}, issn = {1664-302X}, abstract = {Clostridioides difficile infection (CDI) is responsible for around 300,000 hospitalizations yearly in the United States, with the associated monetary cost being billions of dollars. Gut microbiome dysbiosis is known to be important to CDI. To the best of our knowledge, metatranscriptomics (MT) has only been used to characterize gut microbiome composition and function in one prior study involving CDI patients. Therefore, we utilized MT to investigate differences in active community diversity and composition between CDI+ (n = 20) and CDI- (n = 19) samples with respect to microbial taxa and expressed genes. No significant (Kruskal-Wallis, p > 0.05) differences were detected for richness or evenness based on CDI status. However, clustering based on CDI status was significant for both active microbial taxa and expressed genes datasets (PERMANOVA, p ≤ 0.05). Furthermore, differential feature analysis revealed greater expression of the opportunistic pathogens Enterocloster bolteae and Ruminococcus gnavus in CDI+ compared to CDI- samples. When only fungal sequences were considered, the family Saccharomycetaceae expressed more genes in CDI-, while 31 other fungal taxa were identified as significantly (Kruskal-Wallis p ≤ 0.05, log(LDA) ≥ 2) associated with CDI+. We also detected a variety of genes and pathways that differed significantly (Kruskal-Wallis p ≤ 0.05, log(LDA) ≥ 2) based on CDI status. Notably, differential genes associated with biofilm formation were expressed by C. difficile. This provides evidence of another possible contributor to C. difficile's resistance to antibiotics and frequent recurrence in vivo. Furthermore, the greater number of CDI+ associated fungal taxa constitute additional evidence that the mycobiome is important to CDI pathogenesis. Future work will focus on establishing if C. difficile is actively producing biofilms during infection and if any specific fungal taxa are particularly influential in CDI.}, }
@article {pmid38677439, year = {2024}, author = {Luo, X and Hounmanou, YMG and Ndayisenga, F and Yu, Z}, title = {Spontaneous fermentation mitigates the frequency of genes encoding antimicrobial resistance spreading from the phyllosphere reservoir to the diet.}, journal = {The Science of the total environment}, volume = {931}, number = {}, pages = {172712}, doi = {10.1016/j.scitotenv.2024.172712}, pmid = {38677439}, issn = {1879-1026}, mesh = {*Fermentation ; *Microbiota/drug effects ; Bacteria/genetics ; Genes, Bacterial ; Metagenome ; Drug Resistance, Bacterial/genetics ; Drug Resistance, Microbial/genetics ; Vegetables/microbiology ; Humans ; Diet ; }, abstract = {The phyllosphere microbiome of vegetable products constitutes an important reservoir for multidrug resistant bacteria and Antibiotic Resistance Genes (ARG). Vegetable products including fermented products such as Paocai therefore may serve as a shuttle for extrinsic microorganisms with ARGs into the gut of consumers. Here we study the effect of fermentation on Paocai ARG dissemination by metagenomic analysis. Microbial abundance and diversity of the Paocai microbiome were diminished during fermentation, which correlated with the reduction of abundance in ARGs. Specifically, as fermentation progressed, Enterobacterales overtook Pseudomonadales as the predominant ARG carriers, and Lactobacillales and Enterobacteriales became the determinants of Paocai resistome variation. Moreover, the dual effect of microbes and metal resistance genes (MRGs) was the major contributor driving Paocai resistome dynamics. We recovered several metagenome-assembled genomes (MAGs) carrying acquired ARGs in the phyllosphere microbiome. ARGs of potential clinical and epidemiological relevance such as tet M and emrB-qacA, were mainly hosted by non-dominant bacterial genera. Overall, our study provides evidence that changes in microbial community composition by fermentation aid in constraining ARG dispersal from raw ingredients to the human microbiome but does not eliminate them.}, }
@article {pmid38674588, year = {2024}, author = {Brogna, C and Bisaccia, DR and Costanzo, V and Lettieri, G and Montano, L and Viduto, V and Fabrowski, M and Cristoni, S and Prisco, M and Piscopo, M}, title = {Who Is the Intermediate Host of RNA Viruses? A Study Focusing on SARS-CoV-2 and Poliovirus.}, journal = {Microorganisms}, volume = {12}, number = {4}, pages = {}, pmid = {38674588}, issn = {2076-2607}, abstract = {The COVID-19 pandemic has sparked a surge in research on microbiology and virology, shedding light on overlooked aspects such as the infection of bacteria by RNA virions in the animal microbiome. Studies reveal a decrease in beneficial gut bacteria during COVID-19, indicating a significant interaction between SARS-CoV-2 and the human microbiome. However, determining the origins of the virus remains complex, with observed phenomena such as species jumps adding layers to the narrative. Prokaryotic cells play a crucial role in the disease's pathogenesis and transmission. Analyzing previous studies highlights intricate interactions from clinical manifestations to the use of the nitrogen isotope test. Drawing parallels with the history of the Poliovirus underscores the need to prioritize investigations into prokaryotic cells hosting RNA viruses.}, }
@article {pmid38674238, year = {2024}, author = {Hernández-Zulueta, J and Bolaños-Chang, AJ and Santa Cruz-Pavlovich, FJ and Valero Rodríguez, AD and Lizárraga Madrigal, A and Del Rio-Murillo, XI and Navarro-Partida, J and Gonzalez-De la Rosa, A}, title = {Microbial Dynamics in Ophthalmic Health: Exploring the Interplay between Human Microbiota and Glaucoma Pathogenesis.}, journal = {Medicina (Kaunas, Lithuania)}, volume = {60}, number = {4}, pages = {}, pmid = {38674238}, issn = {1648-9144}, mesh = {Humans ; *Glaucoma/microbiology ; *Microbiota/physiology ; *Dysbiosis/complications/immunology ; Mouth/microbiology ; Gastrointestinal Microbiome/physiology ; Eye/microbiology ; Neurodegenerative Diseases/microbiology ; }, abstract = {The human microbiome has a crucial role in the homeostasis and health of the host. These microorganisms along with their genes are involved in various processes, among these are neurological signaling, the maturation of the immune system, and the inhibition of opportunistic pathogens. In this sense, it has been shown that a healthy ocular microbiota acts as a barrier against the entry of pathogens, contributing to the prevention of infections. In recent years, a relationship has been suggested between microbiota dysbiosis and the development of neurodegenerative diseases. In patients with glaucoma, it has been observed that the microbiota of the ocular surface, intraocular cavity, oral cavity, stomach, and gut differ from those observed in healthy patients, which may suggest a role in pathology development, although the evidence remains limited. The mechanisms involved in the relationship of the human microbiome and this neurodegenerative disease remain largely unknown. For this reason, the present review aims to show a broad overview of the influence of the structure and composition of the human oral and gut microbiota and relate its dysbiosis to neurodegenerative diseases, especially glaucoma.}, }
@article {pmid38669195, year = {2024}, author = {Sengupta, S and Pabbaraja, S and Mehta, G}, title = {Natural products from the human microbiome: an emergent frontier in organic synthesis and drug discovery.}, journal = {Organic &amp; biomolecular chemistry}, volume = {22}, number = {20}, pages = {4006-4030}, doi = {10.1039/d4ob00236a}, pmid = {38669195}, issn = {1477-0539}, mesh = {Humans ; *Biological Products/pharmacology/chemistry/chemical synthesis/metabolism ; *Drug Discovery ; *Microbiota/drug effects ; Anti-Bacterial Agents/pharmacology/chemical synthesis/chemistry ; }, abstract = {Often referred to as the "second genome", the human microbiome is at the epicenter of complex inter-habitat biochemical networks like the "gut-brain axis", which has emerged as a significant determinant of cognition, overall health and well-being, as well as resistance to antibiotics and susceptibility to diseases. As part of a broader understanding of the nexus between the human microbiome, diseases and microbial interactions, whether encoded secondary metabolites (natural products) play crucial signalling roles has been the subject of intense scrutiny in the recent past. A major focus of these activities involves harvesting the genomic potential of the human microbiome via bioinformatics guided genome mining and culturomics. Through these efforts, an impressive number of structurally intriguing antibiotics, with enhanced chemical diversity vis-à-vis conventional antibiotics have been isolated from human commensal bacteria, thereby generating considerable interest in their total synthesis and expanding their therapeutic space for drug discovery. These developments augur well for the discovery of new drugs and antibiotics, particularly in the context of challenges posed by mycobacterial resistance and emerging new diseases. The current landscape of various synthetic campaigns and drug discovery initiatives on antibacterial natural products from the human microbiome is captured in this review with an intent to stimulate further activities in this interdisciplinary arena among the new generation.}, }
@article {pmid38668878, year = {2024}, author = {Farfour, E and Vasse, M and Vallée, A}, title = {Oligella spp.: A systematic review on an uncommon urinary pathogen.}, journal = {European journal of clinical microbiology &amp; infectious diseases : official publication of the European Society of Clinical Microbiology}, volume = {43}, number = {6}, pages = {1037-1050}, pmid = {38668878}, issn = {1435-4373}, mesh = {Humans ; *Microbial Sensitivity Tests ; *Urinary Tract Infections/microbiology ; *Anti-Bacterial Agents/pharmacology ; Gram-Negative Bacterial Infections/microbiology/diagnosis ; }, abstract = {BACKGROUND: Oligella is an uncommon Gram-negative coccobacillus that was first thought to belong to the urogenital tract. The genus Oligella comprises two species that were recovered from various samples worldwide.<br><br>METHODS: We perform a systematic review focusing on Oligella microbiological characteristics, habitat, role in Human microbiome and infection, and antimicrobial susceptibility.<br><br>RESULTS: In humans, Oligella is mainly found as part of the microbiome of individuals with predisposing conditions. Oligella were also associated with invasive infections in patients with underlying diseases. Nevertheless, their prevalence remains to determine. Oligella culture requires up to 48&#xa0;h on agar media in vitro, while urinary samples are usually incubated for 24&#xa0;h. Consequently, microbiologists should be prompt to prolong the incubation of agar media when the direct examination showed Gram-negative coccobacilli. Oligella is accurately identified using MALDI-TOF mass spectrometry, but biochemical methods often provided inconsistent results. Specific guidelines for antimicrobial susceptibility testing of Oligella lack but the incubation could require up to 48&#xa0;h of incubation. In contrast to O. urethralis, which is susceptible to third-generation cephalosporin, O. ureolytica is likely resistant to numerous antimicrobials. Genectic determinants of resistance were identified for beta-lactams and aminoglycosides.<br><br>CONCLUSION: Oligella is an uncommon pathogen that can be underrecognized. Microbiologists should be prompt to prolong the incubation of agar media plated with urines when the direct examination showed Gram-negative coccobacilli. Carbapenems should probably be given for the empirical treatment.}, }
@article {pmid38666212, year = {2024}, author = {Pujolassos, M and Susín, A and Calle, ML}, title = {Microbiome compositional data analysis for survival studies.}, journal = {NAR genomics and bioinformatics}, volume = {6}, number = {2}, pages = {lqae038}, pmid = {38666212}, issn = {2631-9268}, abstract = {The growing interest in studying the relationship between the human microbiome and our health has also extended to time-to-event studies where researchers explore the connection between the microbiome and the occurrence of a specific event of interest. The analysis of microbiome obtained through high throughput sequencing techniques requires the use of specialized Compositional Data Analysis (CoDA) methods designed to accommodate its compositional nature. There is a limited availability of statistical tools for microbiome analysis that incorporate CoDA, and this is even more pronounced in the context of survival analysis. To fill this methodological gap, we present coda4microbiome for survival studies, a new methodology for the identification of microbial signatures in time-to-event studies. The algorithm implements an elastic-net penalized Cox regression model adapted to compositional covariates. We illustrate coda4microbiome algorithm for survival studies with a case study about the time to develop type 1 diabetes for non-obese diabetic mice. Our algorithm identified a bacterial signature composed of 21 genera associated with diabetes development. coda4microbiome for survival studies is integrated in the R package coda4microbiome as an extension of the existing functions for cross-sectional and longitudinal studies.}, }
@article {pmid38663540, year = {2024}, author = {Liang, L and Zhang, J and Chen, J and Tian, Y and Li, W and Shi, M and Cheng, S and Zheng, Y and Wang, C and Liu, H and Yang, X and Ye, W}, title = {Bazedoxifene attenuates dextran sodium sulfate-induced colitis in mice through gut microbiota modulation and inhibition of STAT3 and NF-κB pathways.}, journal = {European journal of pharmacology}, volume = {974}, number = {}, pages = {176611}, doi = {10.1016/j.ejphar.2024.176611}, pmid = {38663540}, issn = {1879-0712}, mesh = {Animals ; *Dextran Sulfate ; *NF-kappa B/metabolism ; *STAT3 Transcription Factor/metabolism ; *Colitis/chemically induced/drug therapy/metabolism/microbiology/pathology ; *Gastrointestinal Microbiome/drug effects ; Mice ; *Signal Transduction/drug effects ; Indoles/pharmacology/therapeutic use ; Mice, Inbred C57BL ; Disease Models, Animal ; Colon/drug effects/pathology/metabolism/microbiology ; Male ; Humans ; }, abstract = {Inflammatory bowel disease (IBD) is a chronic and relapsing inflammatory disorder of the gastrointestinal tract for which treatment options remain limited. In this study, we used a dual-luciferase-based screening of an FDA-approved drug library, identifying Bazedoxifene (BZA) as an inhibitor of the NF-κB pathway. We further investigated its therapeutic effects in a dextran sodium sulfate (DSS)-induced colitis model and explored its impact on gut microbiota regulation and the underlying molecular mechanisms. Our results showed that BZA significantly reduced DSS-induced colitis symptoms in mice, evidenced by decreased colon length shortening, lower histological scores, and increased expression of intestinal mucosal barrier-associated proteins, such as Claudin 1, Occludin, Zo-1, Mucin 2 (Muc2), and E-cadherin. Used independently, BZA showed therapeutic effects comparable to those of infliximab (IFX). In addition, BZA modulated the abundance of gut microbiota especially Bifidobacterium pseudolongum, and influenced microbial metabolite production. Crucially, BZA's alleviation of DSS-induced colitis in mice was linked to change in gut microbiota composition, as evidenced by in vivo gut microbiota depletion and fecal microbiota transplantation (FMT) mice model. Molecularly, BZA inhibited STAT3 and NF-κB activation in DSS-induced colitis in mice. In general, BZA significantly reduced DSS-induced colitis in mice through modulating the gut microbiota and inhibiting STAT3 and NF-κB activation, and its independent use demonstrated a therapeutic potential comparable to IFX. This study highlights gut microbiota's role in IBD drug development, offering insights for BZA's future development and its clinical applications.}, }
@article {pmid38658578, year = {2024}, author = {Pedrazzoli, E and Demozzi, M and Visentin, E and Ciciani, M and Bonuzzi, I and Pezzè, L and Lucchetta, L and Maule, G and Amistadi, S and Esposito, F and Lupo, M and Miccio, A and Auricchio, A and Casini, A and Segata, N and Cereseto, A}, title = {CoCas9 is a compact nuclease from the human microbiome for efficient and precise genome editing.}, journal = {Nature communications}, volume = {15}, number = {1}, pages = {3478}, pmid = {38658578}, issn = {2041-1723}, support = {R01 CA230551/CA/NCI NIH HHS/United States ; U01 CA230551/CA/NCI NIH HHS/United States ; }, mesh = {*Gene Editing/methods ; Humans ; *CRISPR-Cas Systems ; Animals ; Mice ; *Microbiota/genetics ; Dependovirus/genetics ; CRISPR-Associated Protein 9/metabolism/genetics ; RNA, Guide, CRISPR-Cas Systems/genetics/metabolism ; Retina/metabolism ; Clostridiales/genetics/enzymology ; HEK293 Cells ; Genetic Vectors/metabolism/genetics ; }, abstract = {The expansion of the CRISPR-Cas toolbox is highly needed to accelerate the development of therapies for genetic diseases. Here, through the interrogation of a massively expanded repository of metagenome-assembled genomes, mostly from human microbiomes, we uncover a large variety (n = 17,173) of type II CRISPR-Cas loci. Among these we identify CoCas9, a strongly active and high-fidelity nuclease with reduced molecular size (1004 amino acids) isolated from an uncultivated Collinsella species. CoCas9 is efficiently co-delivered with its sgRNA through adeno associated viral (AAV) vectors, obtaining efficient in vivo editing in the mouse retina. With this study we uncover a collection of previously uncharacterized Cas9 nucleases, including CoCas9, which enriches the genome editing toolbox.}, }
@article {pmid38651909, year = {2024}, author = {Choi, BI and Fontes Noronha, M and Kaindl, J and Wolfe, AJ}, title = {Complete genome sequences of Aerococcus loyolae ATCC TSD-300[T], Aerococcus mictus ATCC TSD-301[T], and Aerococcus tenax ATCC TSD-302[T].}, journal = {Microbiology resource announcements}, volume = {13}, number = {6}, pages = {e0015624}, pmid = {38651909}, issn = {2576-098X}, support = {//Pathnostics/ ; }, abstract = {Previously identified under the single designation of Aerococcus urinae, three distinct taxonomic species have been distinguished as Aerococcus loyolae, Aerococcus mictus, and Aerococcus tenax. Here, we present the complete genome sequences of the type strains of these species assembled via a combination of short-read and long-read sequencing techniques.Registered at ClinicalTrials.gov (NCT01166438).}, }
@article {pmid38638832, year = {2024}, author = {Filardo, S and Di Pietro, M and Sessa, R}, title = {Current progresses and challenges for microbiome research in human health: a perspective.}, journal = {Frontiers in cellular and infection microbiology}, volume = {14}, number = {}, pages = {1377012}, pmid = {38638832}, issn = {2235-2988}, mesh = {Humans ; RNA, Ribosomal, 16S/genetics ; *Microbiota/genetics ; Metagenome ; Metagenomics ; }, abstract = {It is becoming increasingly clear that the human microbiota, also known as "the hidden organ", possesses a pivotal role in numerous processes involved in maintaining the physiological functions of the host, such as nutrient extraction, biosynthesis of bioactive molecules, interplay with the immune, endocrine, and nervous systems, as well as resistance to the colonization of potential invading pathogens. In the last decade, the development of metagenomic approaches based on the sequencing of the bacterial 16s rRNA gene via Next Generation Sequencing, followed by whole genome sequencing via third generation sequencing technologies, has been one of the great advances in molecular biology, allowing a better profiling of the human microbiota composition and, hence, a deeper understanding of the importance of microbiota in the etiopathogenesis of different pathologies. In this scenario, it is of the utmost importance to comprehensively characterize the human microbiota in relation to disease pathogenesis, in order to develop novel potential treatment or preventive strategies by manipulating the microbiota. Therefore, this perspective will focus on the progress, challenges, and promises of the current and future technological approaches for microbiome profiling and analysis.}, }
@article {pmid38622344, year = {2025}, author = {Sarrazin-Gendron, R and Ghasemloo Gheidari, P and Butyaev, A and Keding, T and Cai, E and Zheng, J and Mutalova, R and Mounthanyvong, J and Zhu, Y and Nazarova, E and Drogaris, C and Erhart, K and ,  and ,  and Brouillette, A and Richard, G and Pitchford, R and Caisse, S and Blanchette, M and McDonald, D and Knight, R and Szantner, A and Waldispühl, J}, title = {Improving microbial phylogeny with citizen science within a mass-market video game.}, journal = {Nature biotechnology}, volume = {43}, number = {1}, pages = {76-84}, pmid = {38622344}, issn = {1546-1696}, support = {DP1 AT010885/AT/NCCIH NIH HHS/United States ; }, mesh = {*Video Games ; Humans ; *Citizen Science ; *Phylogeny ; *RNA, Ribosomal, 16S/genetics ; Microbiota/genetics ; }, abstract = {Citizen science video games are designed primarily for users already inclined to contribute to science, which severely limits their accessibility for an estimated community of 3 billion gamers worldwide. We created Borderlands Science (BLS), a citizen science activity that is seamlessly integrated within a popular commercial video game played by tens of millions of gamers. This integration is facilitated by a novel game-first design of citizen science games, in which the game design aspect has the highest priority, and a suitable task is then mapped to the game design. BLS crowdsources a multiple alignment task of 1 million 16S ribosomal RNA sequences obtained from human microbiome studies. Since its initial release on 7 April 2020, over 4 million players have solved more than 135 million science puzzles, a task unsolvable by a single individual. Leveraging these results, we show that our multiple sequence alignment simultaneously improves microbial phylogeny estimations and UniFrac effect sizes compared to state-of-the-art computational methods. This achievement demonstrates that hyper-gamified scientific tasks attract massive crowds of contributors and offers invaluable resources to the scientific community.}, }
@article {pmid38611633, year = {2024}, author = {Lintala, A and Vapalahti, O and Nousiainen, A and Kantele, A and Hepojoki, J}, title = {Whole Blood as a Sample Matrix in Homogeneous Time-Resolved Assay-Förster Resonance Energy Transfer-Based Antibody Detection.}, journal = {Diagnostics (Basel, Switzerland)}, volume = {14}, number = {7}, pages = {}, pmid = {38611633}, issn = {2075-4418}, support = {FUDIS//Business Finland/ ; TYH2021315, TYH2021343//The Finnish Government Subsidy for Health Science Research/ ; none//The Finnish Medical Association/ ; 1336490, 336439 and 335527//Academy of Finland/ ; }, abstract = {The protein-L-utilizing Förster resonance energy transfer (LFRET) assay enables mix-and-read antibody detection, as demonstrated for sera from patients with, e.g., severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Zika virus, and orthohantavirus infections. In this study, we compared paired serum and whole blood (WB) samples of COVID-19 patients and SARS-CoV-2 vaccine recipients. We found that LFRET also detects specific antibodies in WB samples. In 44 serum-WB pairs from patients with laboratory-confirmed COVID-19, LFRET showed a strong correlation between the sample materials. By analyzing 89 additional WB samples, totaling 133 WB samples, we found that LFRET results were moderately correlated with enzyme-linked immunosorbent assay results for samples collected 2 to 14 months after receiving COVID-19 diagnosis. However, the correlation decreased for samples >14 months after receiving a diagnosis. When comparing the WB LFRET results to neutralizing antibody titers, a strong correlation emerged for samples collected 1 to 14 months after receiving a diagnosis. This study also highlights the versatility of LFRET in detecting antibodies directly from WB samples and suggests that it could be employed for rapidly assessing antibody responses to infectious agents or vaccines.}, }
@article {pmid38605646, year = {2024}, author = {Heston, SM and Hurst, JH and Kelly, MS}, title = {Understanding the influence of the microbiome on childhood infections.}, journal = {Expert review of anti-infective therapy}, volume = {22}, number = {7}, pages = {529-545}, pmid = {38605646}, issn = {1744-8336}, support = {K01 AI173398/AI/NIAID NIH HHS/United States ; K12 HD105253/HD/NICHD NIH HHS/United States ; }, mesh = {Humans ; Child ; *Microbiota/physiology ; *Gastrointestinal Microbiome/physiology ; Adolescent ; Communicable Diseases/microbiology/immunology ; Vaccines/administration &amp; dosage/immunology ; Respiratory Tract Infections/microbiology/immunology ; Disease Susceptibility ; Animals ; Immune System/microbiology ; }, abstract = {INTRODUCTION: The microbiome is known to have a substantial impact on human health and disease. However, the impacts of the microbiome on immune system development, susceptibility to infectious diseases, and vaccine-elicited immune responses are emerging areas of interest.<br><br>AREAS COVERED: In this review, we provide an overview of development of the microbiome during childhood. We highlight available data suggesting that the microbiome is critical to maturation of the immune system and modifies susceptibility to a variety of infections during childhood and adolescence, including respiratory tract infections, Clostridioides difficile infection, and sexually transmitted infections. We discuss currently available and investigational therapeutics that have the potential to modify the microbiome to prevent or treat infections among children. Finally, we review the accumulating evidence that the gut microbiome influences vaccine-elicited immune responses among children.<br><br>EXPERT OPINION: Recent advances in sequencing technologies have led to an explosion of studies associating the human microbiome with the risk and severity of infectious diseases. As our knowledge of the extent to which the microbiome influences childhood infections continues to grow, microbiome-based diagnostics and therapeutics will increasingly be incorporated into clinical practice to improve the prevention, diagnosis, and treatment of infectious diseases among children.}, }
@article {pmid38601152, year = {2024}, author = {Soto-Dávila, M and Langlois Fiorotto, L and Heath, JW and Lumsden, JS and Reid, G and Dixon, B}, title = {The effects of Pediococcus acidilactici MA18/5M on growth performance, gut integrity, and immune response using in vitro and in vivo Pacific salmonid models.}, journal = {Frontiers in immunology}, volume = {15}, number = {}, pages = {1306458}, pmid = {38601152}, issn = {1664-3224}, mesh = {Animals ; *Pediococcus acidilactici ; *Probiotics/pharmacology ; Diet ; *Salmonidae ; Disease Resistance ; }, abstract = {Microbial management is central to aquaculture's efficiency. Pediococcus acidilactici MA18/5M has shown promising results promoting growth, modulation of the immune response, and disease resistance in many fishes. However, the mechanisms through which this strain confers health benefits in fish are poorly understood, particularly in Pacific salmonid models. Briefly, the aims of this study were to i) assess the protective effects of P. acidilactici MA18/5M by examining gut barrier function and the expression of tight junction (TJ) and immune genes in vitro and in vivo, and ii) to determine the protective effects of this strain against a common saltwater pathogen, Vibrio anguillarum J382. An in vitro model of the salmonid gut was employed utilizing the cell line RTgutGC. Barrier formation and integrity assessed by TEER measurements in RTgutGC, showed a significant decrease in resistance in cells exposed only to V. anguillarum J382 for 24 h, but pre-treatment with P. acidilactici MA18/5M for 48 h mitigated these effects. While P. acidilactici MA18/5M did not significantly upregulate tight junction and immune molecules, pre-treatment with this strain protected against pathogen-induced insults to the gut barrier. In particular, the expression of ocldn was significantly induced by V. anguillarum J382, suggesting that this molecule might play a role in the host response against this pathogen. To corroborate these observations in live fish, the effects of P. acidilactici MA18/5M was evaluated in Chinook salmon reared in real aquaculture conditions. Supplementation with P. acidilactici MA18/5M had no effect on Chinook salmon growth parameters after 10 weeks. Interestingly, histopathological results did not show alterations associated with P. acidilactici MA18/5M supplementation, indicating that this strain is safe to be used in the industry. Finally, the expression pattern of transcripts encoding TJ and immune genes in all the treatments suggest that variation in expression is more likely to be due to developmental processes rather than P. acidilactici MA18/5M supplementation. Overall, our results showed that P. acidilactici MA18/5M is a safe strain for use in fish production, however, to assess the effects on growth and immune response previously observed in other salmonid species, an assessment in adult fish is needed.}, }
@article {pmid38600604, year = {2024}, author = {Hong, A and Umar, A and Chen, H and Yu, Z and Huang, J}, title = {Advances in the study of the interaction between schistosome infections and the host's intestinal microorganisms.}, journal = {Parasites &amp; vectors}, volume = {17}, number = {1}, pages = {185}, pmid = {38600604}, issn = {1756-3305}, support = {2023JJ30651//Natural Science Foundation of Hunan Province/ ; 32300051//National Natural Science Foundation of China/ ; }, mesh = {Animals ; Humans ; Schistosoma/physiology ; *Schistosomiasis/pathology ; *Liver Diseases ; }, abstract = {Schistosomiasis, also called bilharziasis, is a neglected tropical disease induced by schistosomes that infects hundreds of millions of people worldwide. In the life cycle of schistosomiasis, eggs are regarded as the main pathogenic factor, causing granuloma formation in the tissues and organs of hosts, which can cause severe gastrointestinal and liver granulomatous immune responses and irreversible fibrosis. Increasing evidence suggests that the gut microbiome influences the progression of schistosomiasis and plays a central role in liver disease via the gut-liver axis. When used as pharmaceutical supplements or adjunctive therapy, probiotics have shown promising results in preventing, mitigating, and even treating schistosomiasis. This review elucidates the potential mechanisms of this three-way parasite-host-microbiome interaction by summarizing schistosome-mediated intestinal flora disorders, local immune changes, and host metabolic changes, and elaborates the important role of the gut microbiome in liver disease after schistosome infection through the gut-liver axis. Understanding the mechanisms behind this interaction may aid in the discovery of probiotics as novel therapeutic targets and sustainable control strategies for schistosomiasis.}, }
@article {pmid38594499, year = {2024}, author = {Franceschetti, L and Lodetti, G and Blandino, A and Amadasi, A and Bugelli, V}, title = {Exploring the role of the human microbiome in forensic identification: opportunities and challenges.}, journal = {International journal of legal medicine}, volume = {138}, number = {5}, pages = {1891-1905}, pmid = {38594499}, issn = {1437-1596}, mesh = {Humans ; *Microbiota ; *Skin/microbiology ; RNA, Ribosomal, 16S/genetics ; DNA Fingerprinting ; Metagenomics/methods ; }, abstract = {Forensic microbiology is rapidly emerging as a novel tool for human identification. The human microbiome, comprising diverse microbial communities including fungi, bacteria, protozoa, and viruses, is unique to each individual, offering a new dimension to forensic investigations. While traditional identification methods primarily rely on DNA profiling and fingerprint analysis, they face limitations when complete DNA or fingerprints profiles are unattainable or degraded. In this context, the microbial signatures of the human skin microbiome present a promising alternative due to their resilience to environmental stresses and individual-specific composition. This review explores the potential of microbiome analysis in forensic human identification, evaluating its applications, advantages, limitations, and future prospects. The uniqueness of an individual's microbial community, particularly the skin microbiota, can provide distinctive biological markers for identification purposes, while technological advancements like 16 S rRNA sequencing and metagenomic shotgun sequencing are enhancing the specificity of microbial identification, enabling detailed analysis of these complex ecological communities. Despite these promising findings, current research has not yet achieved a level of identification probability that could establish microbial analysis as a stand-alone evidence tool. Therefore, it is presently considered ancillary to traditional methods, contributing to a more comprehensive biological profile of individuals.}, }
@article {pmid38593705, year = {2024}, author = {Jian, C and Sorensen, N and Lutter, R and Albers, R and de Vos, W and Salonen, A and Mercenier, A}, title = {The impact of daily supplementation with rhamnogalacturonan-I on the gut microbiota in healthy adults: A randomized controlled trial.}, journal = {Biomedicine &amp; pharmacotherapy = Biomedecine &amp; pharmacotherapie}, volume = {174}, number = {}, pages = {116561}, doi = {10.1016/j.biopha.2024.116561}, pmid = {38593705}, issn = {1950-6007}, mesh = {Humans ; *Pectins/administration &amp; dosage/pharmacology ; *Gastrointestinal Microbiome/drug effects ; Male ; Adult ; Double-Blind Method ; Female ; *Dietary Supplements ; *Healthy Volunteers ; Young Adult ; Rhinovirus/drug effects ; Middle Aged ; Feces/microbiology ; Bifidobacterium/drug effects ; }, abstract = {Pectin and its derivatives have been shown to modulate immune signaling as well as gut microbiota in preclinical studies, which may constitute the mechanisms by which supplementation of specific pectic polysaccharides confers protection against viral respiratory infections. In a double-blind, placebo-controlled rhinovirus (RV16) challenge study, healthy volunteers were randomized to consume placebo (0.0 g/day) (N = 46), low-dose (0.3 g/day) (N = 49) or high-dose (1.5 g/day) (N = 51) of carrot derived rhamnogalacturonan-I (cRG-I) for eight weeks and they were subsequently challenged with RV-16. Here, the effect of 8-week cRG-I supplementation on the gut microbiota was studied. While the overall gut microbiota composition in the population was generally unaltered by this very low dose of fibre, the relative abundance of Bifidobacterium spp. (mainly B. adolescentis and B. longum) was significantly increased by both doses of cRG-1. Moreover, daily supplementation of cRG-I led to a dose-dependent reduction in inter- and intra-individual microbiota heterogeneity, suggesting a stabilizing effect on the gut microbiota. The severity of respiratory symptoms did not directly correlate with the cRG-I-induced microbial changes, but several dominant groups of the Ruminococcaceae family and microbiota richness were positively associated with a reduced and hence desired post-infection response. Thus, the present results on the modulation of the gut microbiota composition support the previously demonstrated immunomodulatory and protective effect of cRG-I during a common cold infection.}, }
@article {pmid38593079, year = {2024}, author = {Zhong, Q and Liao, B and Liu, J and Shen, W and Wang, J and Wei, L and Ma, Y and Dong, PT and Bor, B and McLean, JS and Chang, Y and Shi, W and Cen, L and Wu, M and Liu, J and Li, Y and He, X and Le, S}, title = {Episymbiotic Saccharibacteria TM7x modulates the susceptibility of its host bacteria to phage infection and promotes their coexistence.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {121}, number = {16}, pages = {e2319790121}, pmid = {38593079}, issn = {1091-6490}, support = {R01 DE023810/DE/NIDCR NIH HHS/United States ; R01 GM110243/GM/NIGMS NIH HHS/United States ; R01 AI087946/AI/NIAID NIH HHS/United States ; R01 GM124378/GM/NIGMS NIH HHS/United States ; R01 AI152421/AI/NIAID NIH HHS/United States ; R01 DE030943/DE/NIDCR NIH HHS/United States ; R01 AI132818/AI/NIAID NIH HHS/United States ; R01 DE031274/DE/NIDCR NIH HHS/United States ; S10 OD023603/OD/NIH HHS/United States ; }, mesh = {Humans ; *Bacteriophages/physiology ; Symbiosis ; Bacteria/genetics ; }, abstract = {Bacteriophages (phages) play critical roles in modulating microbial ecology. Within the human microbiome, the factors influencing the long-term coexistence of phages and bacteria remain poorly investigated. Saccharibacteria (formerly TM7) are ubiquitous members of the human oral microbiome. These ultrasmall bacteria form episymbiotic relationships with their host bacteria and impact their physiology. Here, we showed that during surface-associated growth, a human oral Saccharibacteria isolate (named TM7x) protects its host bacterium, a Schaalia odontolytica strain (named XH001) against lytic phage LC001 predation. RNA-Sequencing analysis identified in XH001 a gene cluster with predicted functions involved in the biogenesis of cell wall polysaccharides (CWP), whose expression is significantly down-regulated when forming a symbiosis with TM7x. Through genetic work, we experimentally demonstrated the impact of the expression of this CWP gene cluster on bacterial-phage interaction by affecting phage binding. In vitro coevolution experiments further showed that the heterogeneous populations of TM7x-associated and TM7x-free XH001, which display differential susceptibility to LC001 predation, promote bacteria and phage coexistence. Our study highlights the tripartite interaction between the bacterium, episymbiont, and phage. More importantly, we present a mechanism, i.e., episymbiont-mediated modulation of gene expression in host bacteria, which impacts their susceptibility to phage predation and contributes to the formation of "source-sink" dynamics between phage and bacteria in biofilm, promoting their long-term coexistence within the human microbiome.}, }
@article {pmid38590477, year = {2024}, author = {Vijayan, S and Kandi, V and Palacholla, PS and Rajendran, R and Jarugu, C and Ca, J and Pravallika, M and Reddy, SC and Sucharitha, AS}, title = {Probiotics in Allergy and Immunological Diseases: A Comprehensive Review.}, journal = {Cureus}, volume = {16}, number = {3}, pages = {e55817}, pmid = {38590477}, issn = {2168-8184}, abstract = {Allergy and immunological disorders like autoimmune diseases are vastly prevalent worldwide. These conditions account for a substantial amount of personal and social burden. Such illnesses have lengthy, uncertain, and spotted courses with unpredictable exacerbations. A definite tendency for improving the overall quality of life of individuals suffering from such diseases is crucial to tackling these diseases, especially through diet or lifestyle modification. Further, interventions like microbiome-based therapeutics such as prebiotics or probiotics were explored. Changes in the microbial population were evident during the flare-up of autoimmune and allergic conditions. The realization that the human microbiome is a central player in immunological diseases is a hallmark of its potential usefulness in therapy for such illnesses. This review focuses on the intricate symphony in the orchestra of the human microbiome and the immune system. New therapeutic strategies involving probiotics appear to be the future of personalized medicine. Through this review, we explore the narrative of probiotics and reaffirm their use as therapeutic and preventive agents in immunological disorders.}, }
@article {pmid38590114, year = {2024}, author = {Rezzani, R and Favero, G and Gianò, M and Pinto, D and Labanca, M and van Noorden, CJF and Rinaldi, F}, title = {Transient Receptor Potential Channels in the Healthy and Diseased Blood-Brain Barrier.}, journal = {The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society}, volume = {72}, number = {4}, pages = {199-231}, pmid = {38590114}, issn = {1551-5044}, mesh = {Humans ; *Transient Receptor Potential Channels/metabolism ; Blood-Brain Barrier ; Endothelial Cells/metabolism ; TRPV Cation Channels ; *Nervous System Diseases ; }, abstract = {The large family of transient receptor potential (TRP) channels are integral membrane proteins that function as environmental sensors and act as ion channels after activation by mechanical (touch), physical (heat, pain), and chemical stimuli (pungent compounds such as capsaicin). Most TRP channels are localized in the plasma membrane of cells but some of them are localized in membranes of organelles and function as intracellular Ca[2+]-ion channels. TRP channels are involved in neurological disorders but their precise role(s) and relevance in these disorders are not clear. Endothelial cells of the blood-brain barrier (BBB) express TRP channels such as TRP vanilloid 1-4 and are involved in thermal detection by regulating BBB permeability. In neurological disorders, TRP channels in the BBB are responsible for edema formation in the brain. Therefore, drug design to modulate locally activity of TRP channels in the BBB is a hot topic. Today, the application of TRP channel antagonists against neurological disorders is still limited.}, }
@article {pmid38587593, year = {2024}, author = {Chung, IY and Kim, J and Koh, A}, title = {The Microbiome Matters: Its Impact on Cancer Development and Therapeutic Responses.}, journal = {Journal of microbiology (Seoul, Korea)}, volume = {62}, number = {3}, pages = {137-152}, pmid = {38587593}, issn = {1976-3794}, support = {KFRM 22A0301L1//Korean Fund for Regenerative Medicine (KFRM)/ ; 2023R1A2C1002876//National Research Foundation of Korea (NRF)/ ; 2021R1I1A1A01052756//National Research Foundation of Korea (NRF)/ ; 2021R1A6C101A390//the Basic Science Institute/ ; }, mesh = {Humans ; *Neoplasms/microbiology/therapy ; *Gastrointestinal Microbiome ; *Dysbiosis/microbiology ; Microbiota ; Bacteria/classification/genetics/isolation &amp; purification ; Carcinogenesis ; Immunotherapy ; Mouth/microbiology ; }, abstract = {In the evolving landscape of cancer research, the human microbiome emerges as a pivotal determinant reshaping our understanding of tumorigenesis and therapeutic responses. Advanced sequencing technologies have uncovered a vibrant microbial community not confined to the gut but thriving within tumor tissues. Comprising bacteria, viruses, and fungi, this diverse microbiota displays distinct signatures across various cancers, with most research primarily focusing on bacteria. The correlations between specific microbial taxa within different cancer types underscore their pivotal roles in driving tumorigenesis and influencing therapeutic responses, particularly in chemotherapy and immunotherapy. This review amalgamates recent discoveries, emphasizing the translocation of the oral microbiome to the gut as a potential marker for microbiome dysbiosis across diverse cancer types and delves into potential mechanisms contributing to cancer promotion. Furthermore, it highlights the adverse effects of the microbiome on cancer development while exploring its potential in fortifying strategies for cancer prevention and treatment.}, }
@article {pmid38586050, year = {2024}, author = {Ho, PY and Huang, KC}, title = {Challenges in quantifying functional redundancy and selection in microbial communities.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2024.03.26.586891}, pmid = {38586050}, issn = {2692-8205}, abstract = {Microbiomes can exhibit large variations in species abundances but high reproducibility in abundances of functional units, an observation often considered evidence for functional redundancy. Based on such reduction in functional variability, selection is hypothesized to act on functional units in these ecosystems. However, the link between functional redundancy and selection remains unclear. Here, we show that reduction in functional variability does not always imply selection on functional profiles. We propose empirical null models to account for the confounding effects of statistical averaging and bias toward environment-independent beneficial functions. We apply our models to existing data sets, and find that the abundances of metabolic groups within microbial communities from bromeliad foliage do not exhibit any evidence of the previously hypothesized functional selection. By contrast, communities of soil bacteria or human gut commensals grown in vitro are selected for metabolic capabilities. By separating the effects of averaging and functional bias on functional variability, we find that the appearance of functional selection in gut microbiome samples from the Human Microbiome Project is artifactual, and that there is no evidence of selection for any molecular function represented by KEGG orthology. These concepts articulate a basic framework for quantifying functional redundancy and selection, advancing our understanding of the mapping between microbiome taxonomy and function.}, }
@article {pmid38585738, year = {2024}, author = {Hunter, C and Dia, K and Boykins, J and Perry, K and Banerjee, N and Cuffee, J and Armstrong, E and Morgan, G and Banerjee, HN and Banerjee, A and Bhattacharya, S}, title = {An investigation for phylogenetic characterization of human Pancreatic cancer microbiome by 16SrDNA Sequencing and Bioinformatics techniques.}, journal = {Research square}, volume = {}, number = {}, pages = {}, pmid = {38585738}, issn = {2693-5015}, support = {T34 GM100831/GM/NIGMS NIH HHS/United States ; }, abstract = {Pancreatic cancer is a significant public health concern, with increasing incidence rates and limited treatment options. Recent studies have highlighted the role of the human microbiome, particularly the gut microbiota, in the development and progression of this disease. Microbial dysbiosis, characterized by alterations in the composition and function of the gut microbiota, has been implicated in pancreatic carcinogenesis through mechanisms involving chronic inflammation, immune dysregulation, and metabolic disturbances. Researchers have identified specific microbial signatures associated with pancreatic cancer, offering potential biomarkers for early detection and prognostication. By leveraging advanced sequencing and bioinformatics tools, scientists have delineated differences in the gut microbiota between pancreatic cancer patients and healthy individuals, providing insights into disease pathogenesis and potential diagnostic strategies. Moreover, the microbiome holds promise as a therapeutic target in pancreatic cancer treatment. Interventions aimed at modulating the microbiome, such as probiotics, prebiotics, and fecal microbiota transplantation, have demonstrated potential in enhancing the efficacy of existing cancer therapies, including chemotherapy and immunotherapy. These approaches can influence immune responses, alter tumor microenvironments, and sensitize tumors to treatment, offering new avenues for improving patient outcomes and overcoming therapeutic resistance. Overall, understanding the complex interplay between the microbiome and pancreatic cancer is crucial for advancing our knowledge of disease mechanisms and identifying innovative therapeutic strategies. Here we report phylogenetic analysis of the 16S microbial sequences of the pancreatic cancer mice microbiome and corresponding age matched healthy mice microbiome. We successfully identified differentially abundance of microbiota in the pancreatic cancer.}, }
@article {pmid38585650, year = {2024}, author = {Kiljunen, S and Resch, G}, title = {Editorial: Standards in personalized phage therapy: from phage collection to phage production.}, journal = {Frontiers in cellular and infection microbiology}, volume = {14}, number = {}, pages = {1376386}, doi = {10.3389/fcimb.2024.1376386}, pmid = {38585650}, issn = {2235-2988}, mesh = {*Bacteriophages/genetics ; *Phage Therapy ; Anti-Bacterial Agents ; }, }
@article {pmid38581020, year = {2024}, author = {Douillard, FP and Derman, Y and Jian, C and Korpela, K and Saxén, H and Salonen, A and de Vos, WM and Korkeala, H and Lindström, M}, title = {Case report: Aberrant fecal microbiota composition of an infant diagnosed with prolonged intestinal botulism.}, journal = {Gut pathogens}, volume = {16}, number = {1}, pages = {20}, pmid = {38581020}, issn = {1757-4749}, abstract = {BACKGROUND: Intestinal botulism is primarily reported in small babies as a condition known as infant botulism. The condition results from the ingestion of environmental or foodborne spores of botulinum neurotoxin (BoNT) producing Clostridia, usually Clostridium botulinum, and subsequent spore germination into active botulinum neurotoxinogenic cultures in the gut. It is generally considered that small babies are susceptible to C. botulinum colonization because of their immature gut microbiota. Yet, it is poorly understood which host factors contribute to the clinical outcome of intestinal botulism. We previously reported a case of infant botulism where the infant recovered clinically in six weeks but continued to secrete C. botulinum cells and/or BoNT in the feces for seven months.<br><br>CASE PRESENTATION: To further understand the microbial ecology behind this exceptionally long-lasting botulinum neurotoxinogenic colonization, we characterized the infant fecal microbiota using 16S rRNA gene amplicon sequencing over the course of disease and recovery. C. botulinum could be detected in the infant fecal samples at low levels through the acute phase of the disease and three months after recovery. Overall, we observed a temporal delay in the maturation of the infant fecal microbiota associated with a persistently high-level bifidobacterial population and a low level of Lachnospiraceae, Bacteroidaceae and Ruminococcaceae compared to healthy infants over time.<br><br>CONCLUSION: This study brings novel insights into the infant fecal composition associated with intestinal botulism and provides a basis for a more systematic analysis of the gut microbiota of infants diagnosed with botulism. A better understanding of the gut microbial ecology associated with infant botulism may support the development of prophylactic strategies against this life-threatening disease in small babies.}, }
@article {pmid38579936, year = {2024}, author = {Rivet-Noor, CR and Merchak, AR and Render, C and Gay, NM and Beiter, RM and Brown, RM and Keeler, A and Moreau, GB and Li, S and Olgun, DG and Steigmeyer, AD and Ofer, R and Phan, T and Vemuri, K and Chen, L and Mahoney, KE and Shin, JB and Malaker, SA and Deppmann, C and Verzi, MP and Gaultier, A}, title = {Stress-induced mucin 13 reductions drive intestinal microbiome shifts and despair behaviors.}, journal = {Brain, behavior, and immunity}, volume = {119}, number = {}, pages = {665-680}, pmid = {38579936}, issn = {1090-2139}, support = {R01 DK126446/DK/NIDDK NIH HHS/United States ; T32 GM067543/GM/NIGMS NIH HHS/United States ; T32 GM149444/GM/NIGMS NIH HHS/United States ; R01 DC018842/DC/NIDCD NIH HHS/United States ; R01 DK121915/DK/NIDDK NIH HHS/United States ; T32 GM139787/GM/NIGMS NIH HHS/United States ; T32 NS115657/NS/NINDS NIH HHS/United States ; F31 AI174782/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Male ; Mice ; Behavior, Animal/physiology ; *Depression/metabolism/microbiology ; *Dysbiosis/metabolism/microbiology ; *Gastrointestinal Microbiome/physiology ; Hepatocyte Nuclear Factor 4/metabolism ; Mice, Inbred C57BL ; Mice, Knockout ; Mucins/metabolism ; *Stress, Psychological/metabolism/microbiology ; }, abstract = {Depression is a prevalent psychological condition with limited treatment options. While its etiology is multifactorial, both chronic stress and changes in microbiome composition are associated with disease pathology. Stress is known to induce microbiome dysbiosis, defined here as a change in microbial composition associated with a pathological condition. This state of dysbiosis is known to feedback on depressive symptoms. While studies have demonstrated that targeted restoration of the microbiome can alleviate depressive-like symptoms in mice, translating these findings to human patients has proven challenging due to the complexity of the human microbiome. As such, there is an urgent need to identify factors upstream of microbial dysbiosis. Here we investigate the role of mucin 13 as an upstream mediator of microbiome composition changes in the context of stress. Using a model of chronic stress, we show that the glycocalyx protein, mucin 13, is selectively reduced after psychological stress exposure. We further demonstrate that the reduction of Muc13 is mediated by the Hnf4 transcription factor family. Finally, we determine that deleting Muc13 is sufficient to drive microbiome shifts and despair behaviors. These findings shed light on the mechanisms behind stress-induced microbial changes and reveal a novel regulator of mucin 13 expression.}, }
@article {pmid38577723, year = {2024}, author = {Kozajda, A and Miśkiewicz, E and Jeżak, K}, title = {Zoonotic bacteria in the vicinity of animal farms as a factor disturbing the human microbiome: a review.}, journal = {International journal of occupational medicine and environmental health}, volume = {37}, number = {2}, pages = {138-152}, pmid = {38577723}, issn = {1896-494X}, mesh = {Humans ; Animals ; *Microbiota ; Farms ; Livestock/microbiology ; Zoonoses/microbiology/transmission ; Environmental Exposure/adverse effects ; Air Microbiology ; Bacteria/isolation &amp; purification/classification ; }, abstract = {This review is aimed at summarizing the current state of knowledge about the relationship between environmental exposure to the bioaerosol emitted by intensive livestock farming and changes in the microbiome of people living in livestock farm vicinity. The PubMed, Scopus and Web of Science databases were searched by crossing keywords from the following 3 groups: a) "livestock," "animal farms," "animal breeding"; b) "microbiome," "resistome"; c) "livestock vicinity," "farm vicinity," "neighborhoods and health" in 2010-2022. Literature screening did not reveal any paper related to the full microbiome composition in the population studied. In the study, the authors included 7 papers (5 from the Netherlands, 1 from the USA, and 1 from China). The studies confirmed the carriage of Staphylococcus aureus, including methicillin-resistant S. aureus (MRSA), livestockassociated MRSA (LA-MRSA MC398) and multidrug-resistant S. aureus (MDRSA) in the nasal microbiome of adults and children living within 500-2000 m from a livestock farm. Clostridium difficile, including LA-ribotype RT078 carriage, was detected in the intestinal microbiome of adults living within 500-1000 m. Extended-spectrum β-lactamase (ESBL) producing Enterobacteriaceae were confirmed in the intestinal microbiome of adults living within 500-6200 m. Knowledge on the composition of the microflora of people living in livestock farm vicinity is insufficient to conclude about changes in the microbiome caused by the environmental emission of bioaerosol. The carriage prevalence of the LA-bacteria, including both strains with antimicrobial resistance and antimicrobial resistance genes, confirms the presence of zoonotic bacteria in the human microflora in populations without occupational contact with animals. It cannot be ruled out that zoonotic bacteria, as a component of the microbiome, have a negative impact on people's health. Int J Occup Med Environ Health. 2024;37(2):138-52.}, }
@article {pmid38577200, year = {2024}, author = {Salvadori, M and Rosso, G}, title = {Update on the gut microbiome in health and diseases.}, journal = {World journal of methodology}, volume = {14}, number = {1}, pages = {89196}, pmid = {38577200}, issn = {2222-0682}, abstract = {The Human Microbiome Project, Earth Microbiome Project, and next-generation sequencing have advanced novel genome association, host genetic linkages, and pathogen identification. The microbiome is the sum of the microbes, their genetic information, and their ecological niche. This study will describe how millions of bacteria in the gut affect the human body in health and disease. The gut microbiome changes in relation with age, with an increase in Bacteroidetes and Firmicutes. Host and environmental factors affecting the gut microbiome are diet, drugs, age, smoking, exercise, and host genetics. In addition, changes in the gut microbiome may affect the local gut immune system and systemic immune system. In this study, we discuss how the microbiome may affect the metabolism of healthy subjects or may affect the pathogenesis of metabolism-generating metabolic diseases. Due to the high number of publications on the argument, from a methodologically point of view, we decided to select the best papers published in referred journals in the last 3 years. Then we selected the previously published papers. The major goals of our study were to elucidate which microbiome and by which pathways are related to healthy and disease conditions.}, }
@article {pmid38575895, year = {2024}, author = {Zhang, M and Zhao, Y and Umar, A and Zhang, H and Yang, L and Huang, J and Long, Y and Yu, Z}, title = {Comparative analysis of microbial composition and functional characteristics in dental plaque and saliva of oral cancer patients.}, journal = {BMC oral health}, volume = {24}, number = {1}, pages = {411}, pmid = {38575895}, issn = {1472-6831}, support = {32170071 and 82273466//National Natural Science Foundation of China/ ; }, mesh = {Humans ; Saliva/microbiology ; *Dental Plaque/microbiology ; Bacteria/genetics ; *Mouth Neoplasms ; RNA, Ribosomal, 16S/genetics ; }, abstract = {BACKGROUND: The oral cavity is home to various ecological niches, each with its own unique microbial composition. Understanding the microbial communities and gene composition in different ecological niches within the oral cavity of oral cancer (OC) patients is crucial for determining how these microbial populations contribute to disease progression.<br><br>METHODS: In this study, saliva and dental plaque samples were collected from patients with OC. Metagenomic sequencing was employed to analyze the microbial community classification and functional composition of the different sample groups.<br><br>RESULTS: The results of the study revealed significant differences in both the function and classification of microbial communities between saliva and dental plaque samples. The diversity of microbial species in saliva was found to be higher compared to &#xa0;that in&#xa0;plaque samples. Notably, Actinobacteria were enriched in the dental plaque of OC patients. Furthermore, the study identified several inter-group differential marker species, including Prevotella intermedia, Haemophilus parahaemolyticus, Actinomyces radius, Corynebacterium matruchitii, and Veillonella atypica. Additionally, 1,353 differential genes were annotated into 23 functional pathways. Interestingly, a significant correlation was observed between differentially labeled species and Herpes simplex virus 1 (HSV-1) infection, which may be related to the occurrence and development of cancer.<br><br>CONCLUSIONS: Significant differences in the microbial and genetic composition of saliva and dental plaque samples were observed in OC patients. Furthermore, pathogenic bacteria associated with oral diseases were predominantly enriched in saliva. The identification of inter-group differential biomarkers and pathways provide insights into the relationship between oral microbiota and the occurrence and development of OC.}, }
@article {pmid38575862, year = {2024}, author = {Zhang, M and Zhou, Y and Yao, S and Zhao, Y and Batool, SS and Huang, J and Jiang, L and Yan, D and Yan, W and Yu, Z}, title = {Effect of stress urinary incontinence on vaginal microbial communities.}, journal = {BMC microbiology}, volume = {24}, number = {1}, pages = {112}, pmid = {38575862}, issn = {1471-2180}, support = {32000054 and 32170071//National Natural Science Foundation of China/ ; }, mesh = {Female ; Humans ; *Urinary Incontinence, Stress/etiology ; Dysbiosis/microbiology ; RNA, Ribosomal, 16S/genetics ; Vagina/microbiology ; *Microbiota/genetics ; Lactobacillus/genetics ; Bacteria/genetics ; *Vaginal Diseases/complications ; }, abstract = {BACKGROUND: Postpartum women often experience stress urinary incontinence (SUI) and vaginal microbial dysbiosis, which seriously affect women's physical and mental health. Understanding the relationship between SUI and vaginal microbiota composition may help to prevent vaginal diseases, but research on the potential association between these conditions is limited.<br><br>RESULTS: This study employed 16S rRNA gene sequencing to explore the association between SUI and vaginal dysbiosis. In terms of the vaginal microbiota, both species richness and evenness were significantly higher in the SUI group. Additionally, the results of NMDS and species composition indicated that there were differences in the composition of the vaginal microbiota between the two groups. Specifically, compared to postpartum women without SUI (Non-SUI), the relative abundance of bacteria associated with bacterial dysbiosis, such as Streptococcus, Prevotella, Dialister, and Veillonella, showed an increase, while the relative abundance of Lactobacillus decreased in SUI patients. Furthermore, the vaginal microbial co-occurrence network of SUI patients displayed higher connectivity, complexity, and clustering.<br><br>CONCLUSION: The study highlights the role of Lactobacillus in maintaining vaginal microbial homeostasis. It found a correlation between SUI and vaginal microbiota, indicating an increased risk of vaginal dysbiosis. The findings could enhance our understanding of the relationship between SUI and vaginal dysbiosis in postpartum women, providing valuable insights for preventing bacterial vaginal diseases and improving women's health.}, }
@article {pmid38569469, year = {2024}, author = {Caffrey, EB and Sonnenburg, JL and Devkota, S}, title = {Our extended microbiome: The human-relevant metabolites and biology of fermented foods.}, journal = {Cell metabolism}, volume = {36}, number = {4}, pages = {684-701}, doi = {10.1016/j.cmet.2024.03.007}, pmid = {38569469}, issn = {1932-7420}, support = {R01 DK085025/DK/NIDDK NIH HHS/United States ; }, mesh = {Humans ; *Fermented Foods ; *Microbiota ; *Gastrointestinal Microbiome ; Biology ; }, abstract = {One of the key modes of microbial metabolism occurring in the gut microbiome is fermentation. This energy-yielding process transforms common macromolecules like polysaccharides and amino acids into a wide variety of chemicals, many of which are relevant to microbe-microbe and microbe-host interactions. Analogous transformations occur during the production of fermented foods, resulting in an abundance of bioactive metabolites. In foods, the products of fermentation can influence food safety and preservation, nutrient availability, and palatability and, once consumed, may impact immune and metabolic status, disease expression, and severity. Human signaling pathways perceive and respond to many of the currently known fermented food metabolites, though expansive chemical novelty remains to be defined. Here we discuss several aspects of fermented food-associated microbes and metabolites, including a condensed history, current understanding of their interactions with hosts and host-resident microbes, connections with commercial probiotics, and opportunities for future research on human health and disease and food sustainability.}, }
@article {pmid38567073, year = {2024}, author = {Wojciechowska, D and Salamon, S and Wróblewska-Seniuk, K}, title = {It's time to shed some light on the importance of fungi in neonatal intensive care units: what do we know about the neonatal mycobiome?.}, journal = {Frontiers in microbiology}, volume = {15}, number = {}, pages = {1355418}, pmid = {38567073}, issn = {1664-302X}, abstract = {The 21st century, thanks to the development of molecular methods, including DNA barcoding, using Sanger sequencing, and DNA metabarcoding, based on next-generation sequencing (NGS), is characterized by flourishing research on the human microbiome. Microbial dysbiosis is perceived as a new pathogenetic factor for neonatal diseases. Fungi are crucial, but neglected, components of the neonatal microbiome, which, despite their low abundance, significantly impact morbidity and mortality rates of premature infants hospitalized in Neonatal Intensive Care Units (NICUs). The neonatal mycobiome's composition and effect on health remain poorly studied research areas. Our knowledge about neonatal mycobiome, composed of limited genera, is mainly based on research on the bacterial microbiome. We presume it is influenced by clinical factors, including prematurity, antibiotic therapy, and type of delivery. Understanding these risk factors may be useful in prevention strategies against dysbiosis and invasive fungal infections. Despite the methodological challenges resulting from the biology of the fungal cell, this topic is an attractive area of research that may contribute to more effective treatment, especially of newborns from risk groups. In this mini review, we discuss the current state of knowledge, research gaps, study difficulties, and future research directions on the neonatal mycobiome, concerning potential future clinical applications.}, }
@article {pmid38565750, year = {2024}, author = {Núñez Casal, A}, title = {Race and indigeneity in human microbiome science: microbiomisation and the historiality of otherness.}, journal = {History and philosophy of the life sciences}, volume = {46}, number = {2}, pages = {17}, pmid = {38565750}, issn = {1742-6316}, support = {RYC2022-036985-I//Ministerio de Ciencia e Innovaci&#xf3;n/ ; }, mesh = {Humans ; *Microbiota ; United States ; Racial Groups ; }, abstract = {This article reformulates Stephan Helmreich´s the ¨microbiomisation of race¨ as the historiality of otherness in the foundations of human microbiome science. Through the lens of my ethnographic fieldwork of a transnational community of microbiome scientists that conducted a landmark human microbiome research on indigenous microbes and its affiliated and first personalised microbiome initiative, the American Gut Project, I follow and trace the key actors, experimental systems and onto-epistemic claims in the emergence of human microbiome science a decade ago. In doing so, I show the links between the reinscription of race, comparative research on the microbial genetic variation of human populations and the remining of bioprospected data for personalised medicine. In these unpredictable research movements, the microbiome of non-Western peoples and territories is much more than a side project or a specific approach within the field: it constitutes the nucleus of its experimental system, opening towards subsequent and cumulative research processes and knowledge production in human microbiome science. The article demonstrates that while human microbiome science is articulated upon the microbial 'makeup' of non-wester(nised) communities, societies, and locales, its results and therapeutics are only applicable to medical conditions affecting rich nations (i.e., inflammatory, autoimmune, and metabolic diseases). My reformulation of ¨microbiomisation of race¨ as the condition of possibility of human microbiome science reveals that its individual dimension is sustained by microbial DNA data from human populations through bioprospecting practices and gains meaning through personalised medicine initiatives, informal online networks of pseudoscientific and commodified microbial-related evidence.}, }
@article {pmid38563656, year = {2024}, author = {Zhu, J and Yin, J and Chen, J and Hu, M and Lu, W and Wang, H and Zhang, H and Chen, W}, title = {Integrative analysis with microbial modelling and machine learning uncovers potential alleviators for ulcerative colitis.}, journal = {Gut microbes}, volume = {16}, number = {1}, pages = {2336877}, pmid = {38563656}, issn = {1949-0984}, mesh = {Animals ; Mice ; Humans ; *Colitis, Ulcerative ; *Gastrointestinal Microbiome ; *Inflammatory Bowel Diseases ; *Colitis ; Machine Learning ; }, abstract = {Ulcerative colitis (UC) is a challenging form of inflammatory bowel disease, and its etiology is intricately linked to disturbances in the gut microbiome. To identify the potential alleviators of UC, we employed an integrative analysis combining microbial community modeling with advanced machine learning techniques. Using metagenomics data sourced from the Integrated Human Microbiome Project, we constructed individualized microbiome community models for each participant. Our analysis highlighted a significant decline in both α and β-diversity of strain-level microbial populations in UC subjects compared to controls. Distinct differences were also observed in the predicted fecal metabolite profiles and strain-to-metabolite contributions between the two groups. Using tree-based machine learning models, we successfully identified specific microbial strains and their associated metabolites as potential alleviators of UC. Notably, our experimental validation using a dextran sulfate sodium-induced UC mouse model demonstrated that the administration of Parabacteroides merdae ATCC 43,184 and N-acetyl-D-mannosamine provided notable relief from colitis symptoms. In summary, our study underscores the potential of an integrative approach to identify novel therapeutic avenues for UC, paving the way for future targeted interventions.}, }
@article {pmid38560624, year = {2024}, author = {Wilson, NG and Hernandez-Leyva, A and Schwartz, DJ and Bacharier, LB and Kau, AL}, title = {The gut metagenome harbors metabolic and antibiotic resistance signatures of moderate-to-severe asthma.}, journal = {FEMS microbes}, volume = {5}, number = {}, pages = {xtae010}, pmid = {38560624}, issn = {2633-6685}, support = {F30 DK127584/DK/NIDDK NIH HHS/United States ; K08 AI113184/AI/NIAID NIH HHS/United States ; K08 AI159384/AI/NIAID NIH HHS/United States ; T32 GM007200/GM/NIGMS NIH HHS/United States ; }, abstract = {Asthma is a common allergic airway disease that has been associated with the development of the human microbiome early in life. Both the composition and function of the infant gut microbiota have been linked to asthma risk, but functional alterations in the gut microbiota of older patients with established asthma remain an important knowledge gap. Here, we performed whole metagenomic shotgun sequencing of 95 stool samples from a cross-sectional cohort of 59 healthy and 36 subjects with moderate-to-severe asthma to characterize the metagenomes of gut microbiota in adults and children 6 years and older. Mapping of functional orthologs revealed that asthma contributes to 2.9% of the variation in metagenomic content even when accounting for other important clinical demographics. Differential abundance analysis showed an enrichment of long-chain fatty acid (LCFA) metabolism pathways, which have been previously implicated in airway smooth muscle and immune responses in asthma. We also observed increased richness of antibiotic resistance genes (ARGs) in people with asthma. Several differentially abundant ARGs in the asthma cohort encode resistance to macrolide antibiotics, which are often prescribed to patients with asthma. Lastly, we found that ARG and virulence factor (VF) richness in the microbiome were correlated in both cohorts. ARG and VF pairs co-occurred in both cohorts suggesting that virulence and antibiotic resistance traits are coselected and maintained in the fecal microbiota of people with asthma. Overall, our results show functional alterations via LCFA biosynthetic genes and increases in antibiotic resistance genes in the gut microbiota of subjects with moderate-to-severe asthma and could have implications for asthma management and treatment.}, }
@article {pmid38555606, year = {2024}, author = {Tutelyan, VA and Nikityuk, DB}, title = {[Key challenges in the dietary intake structure and cutting edge technologies for optimizing nutrition to protect the health of the Russian рopulation].}, journal = {Voprosy pitaniia}, volume = {93}, number = {1}, pages = {6-21}, doi = {10.33029/0042-8833-2024-93-1-6-21}, pmid = {38555606}, issn = {0042-8833}, support = {FGMF-2022-0001//The research was carried out using subsidies for the implementation of a state task/ ; }, mesh = {Humans ; *Nutritional Status ; *Food ; Food Safety/methods ; Russia ; Eating ; }, abstract = {This article presents an analysis of some of the results of the work of the Federal Research Center for Nutrition and Biotechnology (Center) in recent years, highlighting the most important, promising areas of Nutrition Science and Food Hygiene that need further development. The priority area of Center functioning is scientific support for the implementation of the Doctrine of Food Security of the Russian Federation (Decree of the President of the Russian Federation dated January 21, 2020 No. 20), Decree of the President of the Russian Federation dated July 21, 2020 No. 474 «On the national development goals of the Russian Federation for the period until 2030 «in terms of ensuring an increase in life expectancy and improving the life quality of the population, the Strategy for Improving the Quality of Food Products in the Russian Federation until 2030 (Order of the Government of the Russian Federation dated June 29, 2016 No. 1364-r). The Center coordinates all research on medical nutrition problems in the Russian Federation within the framework of the work of the Problem Commission on Nutrition Hygiene of the Scientific Council of the Federal Service for Supervision of Consumer Rights Protection and Human Welfare, the Scientific Council of the Russian Academy of Sciences on Medical Nutrition Problems, the Scientific and Technical Committee of the Comprehensive Scientific Program «Priority Research in the Field of Nutrition of the Population», Profile Commission on Dietetics of the Expert Council in the Field of Health of the Ministry of Healthcare of Russian Federation, ensuring the implementation of their results with the participation of members of the Consortium "Healthcare, Nutrition, Demography". The most important area of the Center's work is scientific and expert support in the field of international and national technical regulation of the production and turnover of foods and raw materials, in particular, the work of the Russian national contact point of the Codex Alimentarius Commission (established by FAO and WHO), as well as the work of the Russian side in the Eurasian Economic Commission regarding the preparation of proposals for technical regulations of the Customs Union in the field of food safety, evaluation of draft technical regulations and amendments and additions to them.}, }
@article {pmid38555566, year = {2024}, author = {Kuehnast, T and Kumpitsch, C and Mohammadzadeh, R and Weichhart, T and Moissl-Eichinger, C and Heine, H}, title = {Exploring the human archaeome: its relevance for health and disease, and its complex interplay with the human immune system.}, journal = {The FEBS journal}, volume = {}, number = {}, pages = {}, doi = {10.1111/febs.17123}, pmid = {38555566}, issn = {1742-4658}, support = {COE 7//Austrian Science Fund/ ; P 32697//Austrian Science Fund/ ; SFB F83//Austrian Science Fund/ ; }, abstract = {This Review aims to coalesce existing knowledge on the human archaeome, a less-studied yet critical non-bacterial component of the human microbiome, with a focus on its interaction with the immune system. Despite a largely bacteria-centric focus in microbiome research, archaea present unique challenges and opportunities for understanding human health. We examine the archaeal distribution across different human body sites, such as the lower gastrointestinal tract (LGT), upper aerodigestive tract (UAT), urogenital tract (UGT), and skin. Variability in archaeal composition exists between sites; methanogens dominate the LGT, while Nitrososphaeria are prevalent on the skin and UAT. Archaea have yet to be classified as pathogens but show associations with conditions such as refractory sinusitis and vaginosis. In the LGT, methanogenic archaea play critical metabolic roles by converting bacterial end-products into methane, correlating with various health conditions, including obesity and certain cancers. Finally, this work looks at the complex interactions between archaea and the human immune system at the molecular level. Recent research has illuminated the roles of specific archaeal molecules, such as RNA and glycerolipids, in stimulating immune responses via innate immune receptors like Toll-like receptor 8 (TLR8) and 'C-type lectin domain family 4 member E' (CLEC4E; also known as MINCLE). Additionally, metabolic by-products of archaea, specifically methane, have demonstrated immunomodulatory effects through anti-inflammatory and anti-oxidative pathways. Despite these advancements, the mechanistic underpinnings of how archaea influence immune activity remain a fertile area for further investigation.}, }
@article {pmid38553666, year = {2024}, author = {Ma, ZS}, title = {Towards a unified medical microbiome ecology of the OMU for metagenomes and the OTU for microbes.}, journal = {BMC bioinformatics}, volume = {25}, number = {1}, pages = {137}, pmid = {38553666}, issn = {1471-2105}, mesh = {Animals ; Humans ; Metagenome ; *Microbiota/genetics ; *Gastrointestinal Microbiome ; Biodiversity ; Sequence Analysis, DNA ; Metagenomics/methods ; }, abstract = {BACKGROUND: Metagenomic sequencing technologies offered unprecedented opportunities and also challenges to microbiology and microbial ecology particularly. The technology has revolutionized the studies of microbes and enabled the high-profile human microbiome and earth microbiome projects. The terminology-change from microbes to microbiomes signals that our capability to count and classify microbes (microbiomes) has achieved the same or similar level as we can for the biomes (macrobiomes) of plants and animals (macrobes). While the traditional investigations of macrobiomes have usually been conducted through naturalists' (Linnaeus &amp; Darwin) naked eyes, and aerial and satellite images (remote-sensing), the large-scale investigations of microbiomes have been made possible by DNA-sequencing-based metagenomic technologies. Two major types of metagenomic sequencing technologies-amplicon sequencing and whole-genome (shotgun sequencing)-respectively generate two contrastingly different categories of metagenomic reads (data)-OTU (operational taxonomic unit) tables representing microorganisms and OMU (operational metagenomic unit), a new term coined in this article to represent various cluster units of metagenomic genes.<br><br>RESULTS: The ecological science of microbiomes based on the OTU representing microbes has been unified with the classic ecology of macrobes (macrobiomes), but the unification based on OMU representing metagenomes has been rather limited. In a previous series of studies, we have demonstrated the applications of several classic ecological theories (diversity, composition, heterogeneity, and biogeography) to the studies of metagenomes. Here I push the envelope for the unification of OTU and OMU again by demonstrating the applications of metacommunity assembly and ecological networks to the metagenomes of human gut microbiomes. Specifically, the neutral theory of biodiversity (Sloan's near neutral model), Ning et al.stochasticity framework, core-periphery network, high-salience skeleton network, special trio-motif, and positive-to-negative ratio are applied to analyze the OMU tables from whole-genome sequencing technologies, and demonstrated with seven human gut metagenome datasets from the human microbiome project.<br><br>CONCLUSIONS: All of the ecological theories demonstrated previously and in this article, including diversity, composition, heterogeneity, stochasticity, and complex network analyses, are equally applicable to OMU metagenomic analyses, just as to OTU analyses. Consequently, I strongly advocate the unification of OTU/OMU (microbiomes) with classic ecology of plants and animals (macrobiomes) in the context of medical ecology.}, }
@article {pmid38550775, year = {2024}, author = {Monteiro, JS and Kaushik, K and de Arruda, JAA and Georgakopoulou, E and Vieira, AT and Silva, TA and Devadiga, D and Anyanechi, CE and Shetty, S}, title = {Fungal footprints in oral cancer: unveiling the oral mycobiome.}, journal = {Frontiers in oral health}, volume = {5}, number = {}, pages = {1360340}, pmid = {38550775}, issn = {2673-4842}, abstract = {Oral squamous cell carcinoma (OSCC) is the most common type of head and neck cancer, with a high mortality rate. There is growing evidence supporting a link between oral cancer and the microbiome. The microbiome can impact various aspects of cancer, such as pathogenesis, diagnosis, treatment, and prognosis. While there is existing information on bacteria and its connection to oral cancer, the fungi residing in the oral cavity represent a significant component of the microbiome that remains in its early stages of exploration and understanding. Fungi comprise a minuscule part of the human microbiome called the mycobiome. Mycobiome is ubiquitous in the human body but a weakened immune system offers a leeway space for fungi to showcase its virulence. The role of mycobiome as a colonizer, facilitator, or driver of carcinogenesis is still ambiguous. Reactivating the mycobiome that undergoes collateral damage associated with cancer treatment can be watershed event in cancer research. The coordinated, virulent, non-virulent behavior of the fungi once they reach a critical density must be hacked, considering its diagnostic, prognostic and therapeutic implications in cancer. This review highlights the diversity of the mycobiome and its potential role in oral cancer.}, }
@article {pmid38549112, year = {2024}, author = {Edwin, NR and Fitzpatrick, AH and Brennan, F and Abram, F and O'Sullivan, O}, title = {An in-depth evaluation of metagenomic classifiers for soil microbiomes.}, journal = {Environmental microbiome}, volume = {19}, number = {1}, pages = {19}, pmid = {38549112}, issn = {2524-6372}, support = {SFI/16/RC/3835//VistaMilk/ ; Ref: 2020019//Teagasc Walsh Scholarship Programme/ ; }, abstract = {BACKGROUND: Recent endeavours in metagenomics, exemplified by projects such as the human microbiome project and TARA Oceans, have illuminated the complexities of microbial biomes. A robust bioinformatic pipeline and meticulous evaluation of their methodology have contributed to the success of these projects. The soil environment, however, with its unique challenges, requires a specialized methodological exploration to maximize microbial insights. A notable limitation in soil microbiome studies is the dearth of soil-specific reference databases available to classifiers that emulate the complexity of soil communities. There is also a lack of in-vitro mock communities derived from soil strains that can be assessed for taxonomic classification accuracy.<br><br>RESULTS: In this study, we generated a custom in-silico mock community containing microbial genomes commonly observed in the soil microbiome. Using this mock community, we simulated shotgun sequencing data to evaluate the performance of three leading metagenomic classifiers: Kraken2 (supplemented with Bracken, using a custom database derived from GTDB-TK genomes along with its own default database), Kaiju, and MetaPhlAn, utilizing their respective default databases for a robust analysis. Our results highlight the importance of optimizing taxonomic classification parameters, database selection, as well as analysing trimmed reads and contigs. Our study showed that classifiers tailored to the specific taxa present in our samples led to fewer errors compared to broader databases including microbial eukaryotes, protozoa, or human genomes, highlighting the effectiveness of targeted taxonomic classification. Notably, an optimal classifier performance was achieved when applying a relative abundance threshold of 0.001% or 0.005%. The Kraken2 supplemented with bracken, with a custom database demonstrated superior precision, sensitivity, F1 score, and overall sequence classification. Using a custom database, this classifier classified 99% of in-silico reads and 58% of real-world soil shotgun reads, with the latter identifying previously overlooked phyla using a custom database.<br><br>CONCLUSION: This study underscores the potential advantages of in-silico methodological optimization in metagenomic analyses, especially when deciphering the complexities of soil microbiomes. We demonstrate that the choice of classifier and database significantly impacts microbial taxonomic profiling. Our findings suggest that employing Kraken2 with Bracken, coupled with a custom database of GTDB-TK genomes and fungal genomes at a relative abundance threshold of 0.001% provides optimal accuracy in soil shotgun metagenome analysis.}, }
@article {pmid38543670, year = {2024}, author = {Tosado-Rodríguez, E and Alvarado-Vélez, I and Romaguera, J and Godoy-Vitorino, F}, title = {Vaginal Microbiota and HPV in Latin America: A Narrative Review.}, journal = {Microorganisms}, volume = {12}, number = {3}, pages = {}, pmid = {38543670}, issn = {2076-2607}, support = {U54 CA096297/CA/NCI NIH HHS/United States ; U54 MD007587/MD/NIMHD NIH HHS/United States ; U54MD007600/MD/NIMHD NIH HHS/United States ; P20GM103475/GM/NIGMS NIH HHS/United States ; U54 MD007600/MD/NIMHD NIH HHS/United States ; CA096297/CA/NCI NIH HHS/United States ; U54MD007587/GM/NIGMS NIH HHS/United States ; P20 GM103475/GM/NIGMS NIH HHS/United States ; }, abstract = {With the expansion of human microbiome studies in the last 15 years, we have realized the immense implications of microbes in human health. The human holobiont is now accepted, given the commensal relationships with bacteria, fungi, parasites, viruses, and human cells. The cervicovaginal microbiota is a specific case within the human microbiome where diversity is lower to maintain a chemical barrier of protection against infections. This narrative review focuses on the vaginal microbiome. It summarizes key findings on how native bacteria protect women from disease or predispose them to damaging inflammatory processes with an emphasis on the role of HPV infections in Latin America, one of the world's regions with the highest cervical cancer prevalence.}, }
@article {pmid38543514, year = {2024}, author = {Efremova, I and Maslennikov, R and Medvedev, O and Kudryavtseva, A and Avdeeva, A and Krasnov, G and Romanikhin, F and Diatroptov, M and Fedorova, M and Poluektova, E and Levshina, A and Ivashkin, V}, title = {Gut Microbiota and Biomarkers of Intestinal Barrier Damage in Cirrhosis.}, journal = {Microorganisms}, volume = {12}, number = {3}, pages = {}, pmid = {38543514}, issn = {2076-2607}, abstract = {Gut dysbiosis and subclinical intestinal damage are common in cirrhosis. The aim of this study was to examine the association of intestinal damage biomarkers (diamine oxidase [DAO], claudin 3, and intestinal fatty acid binding protein [I-FABP; FABP2]) with the state of the gut microbiota in cirrhosis. The blood levels of DAO were inversely correlated with blood levels of claudin 3, lipopolysaccharide (LPS), presepsin, TNF-α, and the severity of cirrhosis according to Child-Pugh scores. The blood level of I-FABP was directly correlated with the blood level of claudin 3 but not with that of DAO. Patients with small intestinal bacterial overgrowth (SIBO) had lower DAO levels than patients without SIBO. There was no significant difference in claudin 3 levels and I-FABP detection rates between patients with and without SIBO. The DAO level was directly correlated with the abundance of Akkermansiaceae, Akkermansia, Allisonella, Clostridiaceae, Dialister, Lactobacillus, Muribaculaceae, Negativibacillus, Ruminococcus, Thiomicrospiraceae, Verrucomicrobiae, and Verrucomicrobiota; and it was inversely correlated with the abundance of Anaerostipes, Erysipelatoclostridium, and Vibrio. The I-FABP level was directly correlated with Anaerostipes, Bacteroidia, Bacteroidota, Bilophila, Megamonas, and Selenomonadaceae; and it was inversely correlated with the abundance of Brucella, Pseudomonadaceae, Pseudomonas, and Vibrionaceae. The claudin 3 level was directly correlated with Anaerostipes abundance and was inversely correlated with the abundance of Brucella, Coriobacteriia, Eggerthellaceae, and Lactobacillus.}, }
@article {pmid38542770, year = {2024}, author = {Nikoloudaki, O and Pinto, D and Acin Albiac, M and Celano, G and Da Ros, A and De Angelis, M and Rinaldi, F and Gobbetti, M and Di Cagno, R}, title = {Exploring the Gut Microbiome and Metabolome in Individuals with Alopecia Areata Disease.}, journal = {Nutrients}, volume = {16}, number = {6}, pages = {}, pmid = {38542770}, issn = {2072-6643}, mesh = {Adult ; Humans ; *Gastrointestinal Microbiome/genetics ; *Alopecia Areata ; Metabolome ; Feces/chemistry ; Biomarkers/analysis ; RNA, Ribosomal, 16S/genetics ; }, abstract = {In recent years, heightened attention has been devoted to unravelling the intricate interplay between genetic and environmental factors shaping the gut microbiota and its significance for human health. This study delves into exploring the plausible connection between Alopecia Areata (AA), an autoimmune disease, and the dynamics of the gut microbiome. Examining a cohort of healthy adults and individuals with AA, both the gut microbiota composition and volatile organic compound (VOC) metabolites from faeces and urine were analysed. While overall microbiota composition showed no significant differences, intra-individual variability revealed distinctions related to age, gender, and pathology status, with AA individuals exhibiting reduced species richness and evenness. Differential abundance analysis identified microbial biomarkers for AA, notably Firmicutes, Lachnospirales, and Blautia, while Coprococcus stood out for healthy individuals. The Data Integration Analysis for Biomarker discovery using Latent Components (DIABLO) method further supported these findings including metabolite biomarkers, such as esters of branched chain fatty acids and branched chain amino acids as predictors for AA, suggesting potential links to oxidative stress. Despite certain limitations, the study highlights the complexity of the gut microbiome and its metabolites in the context of AA, while the biomarkers identified could be useful starting points for upcoming studies.}, }
@article {pmid38542455, year = {2024}, author = {Mak, AL and Augustijn, QJJ and Heymann, CJF and Havik, S and Verdoes, X and Rios-Morales, M and Bosmans, LA and Verheij, J and Meijnikman, AS and de Jonge, PA and Herrema, H and de Vos, WM and Nieuwdorp, M and Grefhorst, A and Holleboom, AG}, title = {Anaerobutyricum soehngenii Reduces Hepatic Lipogenic Pathways and Increases Intestinal Gluconeogenic Gene Expression in Metabolic-Dysfunction-Associated Steatotic Liver Disease (MASLD) Mice.}, journal = {International journal of molecular sciences}, volume = {25}, number = {6}, pages = {}, pmid = {38542455}, issn = {1422-0067}, mesh = {Male ; Animals ; Mice ; Mice, Inbred C57BL ; Base Composition ; Gluconeogenesis ; Phylogeny ; RNA, Ribosomal, 16S ; Sequence Analysis, DNA ; *Fatty Liver/etiology/genetics ; *Metabolic Diseases ; Butyrates ; Gene Expression ; Phosphatidate Phosphatase ; *Clostridiales ; }, abstract = {Metabolic-dysfunction-associated steatotic liver disease (MASLD) is a growing health problem for which no therapy exists to date. The modulation of the gut microbiome may have treatment potential for MASLD. Here, we investigated Anaerobutyricum soehngenii, a butyrate-producing anaerobic bacterium with beneficial effects in metabolic syndrome, in a diet-induced MASLD mouse model. Male C57BL/6J mice received a Western-type high-fat diet and water with 15% fructose (WDF) to induce MASLD and were gavaged with A. soehngenii (10[8] or 10[9] colony-forming units (CFU) 3 times per week) or a placebo for 6 weeks. The A. soehngenii gavage increased the cecal butyrate concentrations. Although there was no effect on histological MASLD scores, A. soehngenii improved the glycemic response to insulin. In the liver, the WDF-associated altered expression of three genes relevant to the MASLD pathophysiology was reversed upon treatment with A. soehngenii: Lipin-1 (Lpin1), insulin-like growth factor binding protein 1 (Igfbp1) and Interleukin 1 Receptor Type 1 (Il1r1). A. soehngenii administration also increased the intestinal expression of gluconeogenesis and fructolysis genes. Although these effects did not translate into significant histological improvements in MASLD, these results provide a basis for combined gut microbial approaches to induce histological improvements in MASLD.}, }
@article {pmid38542265, year = {2024}, author = {Uzelac, M and Xin, R and Ongkeko, WM}, title = {Microbiome Dysbiosis Is Associated with Castration Resistance and Cancer Stemness in Metastatic Prostate Cancer.}, journal = {International journal of molecular sciences}, volume = {25}, number = {6}, pages = {}, pmid = {38542265}, issn = {1422-0067}, support = {RG096651//UC San Diego Academic Senate/ ; }, mesh = {Male ; Humans ; *Prostatic Neoplasms, Castration-Resistant/pathology ; Proto-Oncogene Proteins c-akt/metabolism ; Phosphatidylinositol 3-Kinases ; Dysbiosis ; Castration ; Receptors, Androgen/metabolism ; }, abstract = {Prostate cancer is the second leading cause of death in males in America, with advanced prostate cancers exhibiting a 5-year survival rate of only 32%. Castration resistance often develops during the course of treatment, but its pathogenesis is poorly understood. This study explores the human microbiome for its implications in castration resistance and metastasis in prostate cancer. RNA sequencing data were downloaded for the bone and soft tissue biopsies of patients with metastatic castration-resistant prostate cancer. These included both metastatic and adjacent normal biopsies. These sequences were mapped to bacterial sequences, yielding species-level counts. A vast majority of species were found to be significantly underabundant in the CRPC samples. Of these, numerous were found to correlate with the expression of known markers of castration resistance, including AR, PI3K, and AKT. Castration resistance-associated signaling pathways were also enriched with these species, including PI3K-AKT signaling and endocrine resistance. For their implications in cancer aggression and metastasis, cancer stem cell markers were further explored for a relation to these species. EGFR and SLC3A2 were widely downregulated, with a greater abundance of most species. Our results suggest that the microbiome is heavily associated with castration resistance and stemness in prostate cancer. By considering the microbiome's importance in these factors, we may better understand the highly aggressive and highly invasive nature of castration-resistant prostate cancer, allowing for the needed improvements in the treatment of this disease.}, }
@article {pmid38530031, year = {2024}, author = {Cao, B and Wang, X and Yin, W and Gao, Z and Xia, B}, title = {The human microbiota is a beneficial reservoir for SARS-CoV-2 mutations.}, journal = {mBio}, volume = {15}, number = {5}, pages = {e0318723}, pmid = {38530031}, issn = {2150-7511}, support = {22QA1411000//STCSM | Science and Technology Innovation Plan Of Shanghai Science and Technology Commission/ ; }, mesh = {Humans ; *SARS-CoV-2/genetics/immunology ; *Mutation ; *COVID-19/virology/immunology ; *Spike Glycoprotein, Coronavirus/genetics/immunology ; *Microbiota/genetics ; Bacteria/genetics/classification ; }, abstract = {UNLABELLED: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mutations are rapidly emerging. In particular, beneficial mutations in the spike (S) protein, which can either make a person more infectious or enable immunological escape, are providing a significant obstacle to the prevention and treatment of pandemics. However, how the virus acquires a high number of beneficial mutations in a short time remains a mystery. We demonstrate here that variations of concern may be mutated due in part to the influence of the human microbiome. We searched the National Center for Biotechnology Information database for homologous fragments (HFs) after finding a mutation and the six neighboring amino acids in a viral mutation fragment. Among the approximate 8,000 HFs obtained, 61 mutations in S and other outer membrane proteins were found in bacteria, accounting for 62% of all mutation sources, which is 12-fold higher than the natural variable proportion. A significant proportion of these bacterial species-roughly 70%-come from the human microbiota, are mainly found in the lung or gut, and share a composition pattern with COVID-19 patients. Importantly, SARS-CoV-2 RNA-dependent RNA polymerase replicates corresponding bacterial mRNAs harboring mutations, producing chimeric RNAs. SARS-CoV-2 may collectively pick up mutations from the human microbiota that change the original virus's binding sites or antigenic determinants. Our study clarifies the evolving mutational mechanisms of SARS-CoV-2.<br><br>IMPORTANCE: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mutations are rapidly emerging, in particular advantageous mutations in the spike (S) protein, which either increase transmissibility or lead to immune escape and are posing a major challenge to pandemic prevention and treatment. However, how the virus acquires a high number of advantageous mutations in a short time remains a mystery. Here, we provide evidence that the human microbiota is a reservoir of advantageous mutations and aids mutational evolution and host adaptation of SARS-CoV-2. Our findings demonstrate a conceptual breakthrough on the mutational evolution mechanisms of SARS-CoV-2 for human adaptation. SARS-CoV-2 may grab advantageous mutations from the widely existing microorganisms in the host, which is undoubtedly an "efficient" manner. Our study might open a new perspective to understand the evolution of virus mutation, which has enormous implications for comprehending the trajectory of the COVID-19 pandemic.}, }
@article {pmid38528457, year = {2024}, author = {Buetas, E and Jordán-López, M and López-Roldán, A and D'Auria, G and Martínez-Priego, L and De Marco, G and Carda-Diéguez, M and Mira, A}, title = {Full-length 16S rRNA gene sequencing by PacBio improves taxonomic resolution in human microbiome samples.}, journal = {BMC genomics}, volume = {25}, number = {1}, pages = {310}, pmid = {38528457}, issn = {1471-2164}, support = {PRE2019-088126//Spanish Ministry of Science and Innovation/ ; RTI2018- 102032-B-I00//The Spanish Ministry of Innovation and Science/ ; }, mesh = {Humans ; RNA, Ribosomal, 16S/genetics ; Genes, rRNA ; Phylogeny ; Sequence Analysis, DNA/methods ; *Microbiota/genetics ; High-Throughput Nucleotide Sequencing/methods ; }, abstract = {BACKGROUND: Sequencing variable regions of the 16S rRNA gene (≃300 bp) with Illumina technology is commonly used to study the composition of human microbiota. Unfortunately, short reads are unable to differentiate between highly similar species. Considering that species from the same genus can be associated with health or disease it is important to identify them at the lowest possible taxonomic rank. Third-generation sequencing platforms such as PacBio SMRT, increase read lengths allowing to sequence the whole gene with the maximum taxonomic resolution. Despite its potential, full length 16S rRNA gene sequencing is not widely used yet. The aim of the current study was to compare the sequencing output and taxonomic annotation performance of the two approaches (Illumina short read sequencing and PacBio long read sequencing of 16S rRNA gene) in different human microbiome samples. DNA from saliva, oral biofilms (subgingival plaque) and faeces of 9 volunteers was isolated. Regions V3-V4 and V1-V9 were amplified and sequenced by Illumina Miseq and by PacBio Sequel II sequencers, respectively.<br><br>RESULTS: With both platforms, a similar percentage of reads was assigned to the genus level (94.79% and 95.06% respectively) but with PacBio a higher proportion of reads were further assigned to the species level (55.23% vs 74.14%). Regarding overall bacterial composition, samples clustered by niche and not by sequencing platform. In addition, all genera with&#x2009;>&#x2009;0.1% abundance were detected in both platforms for all types of samples. Although some genera such as Streptococcus tended to be observed at higher frequency in PacBio than in Illumina (20.14% vs 14.12% in saliva, 10.63% vs 6.59% in subgingival plaque biofilm samples) none of the differences were statistically significant when correcting for multiple testing.<br><br>CONCLUSIONS: The results presented in the current manuscript suggest that samples sequenced using Illumina and PacBio are mostly comparable. Considering that PacBio reads were assigned at the species level with higher accuracy than Illumina, our data support the use of PacBio technology for future microbiome studies, although a higher cost is currently required to obtain an equivalent number of reads per sample.}, }
@article {pmid38528097, year = {2024}, author = {Wang, B and Sun, F and Luan, Y}, title = {Comparison of the effectiveness of different normalization methods for metagenomic cross-study phenotype prediction under heterogeneity.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {7024}, pmid = {38528097}, issn = {2045-2322}, support = {2018YFA0703900//National Key Research and Development Program of China/ ; 2018YFA0703900//National Key Research and Development Program of China/ ; 11971264//National Science Foundation of China/ ; 11971264//National Science Foundation of China/ ; }, mesh = {Humans ; *Microbiota/genetics ; Metagenome ; Metagenomics ; Research Design ; Phenotype ; }, abstract = {The human microbiome, comprising microorganisms residing within and on the human body, plays a crucial role in various physiological processes and has been linked to numerous diseases. To analyze microbiome data, it is essential to account for inherent heterogeneity and variability across samples. Normalization methods have been proposed to mitigate these variations and enhance comparability. However, the performance of these methods in predicting binary phenotypes remains understudied. This study systematically evaluates different normalization methods in microbiome data analysis and their impact on disease prediction. Our findings highlight the strengths and limitations of scaling, compositional data analysis, transformation, and batch correction methods. Scaling methods like TMM show consistent performance, while compositional data analysis methods exhibit mixed results. Transformation methods, such as Blom and NPN, demonstrate promise in capturing complex associations. Batch correction methods, including BMC and Limma, consistently outperform other approaches. However, the influence of normalization methods is constrained by population effects, disease effects, and batch effects. These results provide insights for selecting appropriate normalization approaches in microbiome research, improving predictive models, and advancing personalized medicine. Future research should explore larger and more diverse datasets and develop tailored normalization strategies for microbiome data analysis.}, }
@article {pmid38526734, year = {2024}, author = {Wan, X and Skurnik, M}, title = {Multidisciplinary Methods for Screening Toxic Proteins from Phages and Their Potential Molecular Targets.}, journal = {Methods in molecular biology (Clifton, N.J.)}, volume = {2793}, number = {}, pages = {237-256}, pmid = {38526734}, issn = {1940-6029}, mesh = {*Bacteriophages/genetics ; Genomics ; Bacteria ; Computational Biology/methods ; Bacterial Proteins/genetics ; }, abstract = {This chapter presents a comprehensive methodology for the identification, characterization, and functional analyses of potentially toxic hypothetical proteins of unknown function (toxHPUFs) in phages. The methods begin with in vivo toxicity verification of toxHPUFs in bacterial hosts, utilizing conventional drop tests and following growth curves. Computational methods for structural and functional predictions of toxHPUFs are outlined, incorporating the use of tools such as Phyre2, HHpred, and AlphaFold2. To ascertain potential targets, a comparative genomic approach is described using bioinformatics toolkits for sequence alignment and functional annotation. Moreover, steps are provided to predict protein-protein interactions and visualizing these using PyMOL. The culmination of these methods equips researchers with an effective pipeline to identify and analyze toxHPUFs and their potential targets, laying the groundwork for future experimental confirmations.}, }
@article {pmid38522483, year = {2024}, author = {Bijla, M and Saini, SK and Pathak, AK and Bharadwaj, KP and Sukhavasi, K and Patil, A and Saini, D and Yadav, R and Singh, S and Leeuwenburgh, C and Kumar, P}, title = {Microbiome interactions with different risk factors in development of myocardial infarction.}, journal = {Experimental gerontology}, volume = {189}, number = {}, pages = {112409}, doi = {10.1016/j.exger.2024.112409}, pmid = {38522483}, issn = {1873-6815}, mesh = {Humans ; *Gastrointestinal Microbiome ; *Myocardial Infarction ; *Microbiota ; Risk Factors ; *Hypertension ; }, abstract = {Among all non-communicable diseases, Cardiovascular Diseases (CVDs) stand as the leading global cause of mortality. Within this spectrum, Myocardial Infarction (MI) strikingly accounts for over 15 % of all deaths. The intricate web of risk factors for MI, comprising family history, tobacco use, oral health, hypertension, nutritional pattern, and microbial infections, is firmly influenced by the human gut and oral microbiota, their diversity, richness, and dysbiosis, along with their respective metabolites. Host genetic factors, especially allelic variations in signaling and inflammatory markers, greatly affect the progression or severity of the disease. Despite the established significance of the human microbiome-nutrient-metabolite interplay in associations with CVDs, the unexplored terrain of the gut-heart-oral axis has risen as a critical knowledge gap. Moreover, the pivotal role of the microbiome and the complex interplay with host genetics, compounded by age-related changes, emerges as an area of vital importance in the development of MI. In addition, a distinctive disease susceptibility and severity influenced by gender-based or ancestral differences, adds a crucial insights to the association with increased mortality. Here, we aimed to provide an overview on interactions of microbiome (oral and gut) with major risk factors (tobacco use, alcohol consumption, diet, hypertension host genetics, gender, and aging) in the development of MI and therapeutic regulation.}, }
@article {pmid38513074, year = {2024}, author = {Khawaja, T and Kajova, M and Levonen, I and Pietilä, JP and Välimaa, H and Paajanen, J and Pakkanen, SH and Patjas, A and Montonen, R and Miettinen, S and Virtanen, J and Smura, T and Sironen, T and Fagerlund, R and Ugurlu, H and Iheozor-Ejiofor, R and Saksela, K and Vahlberg, T and Ranki, A and Vierikko, A and Ihalainen, J and Vapalahti, O and Kantele, A}, title = {Double-blinded, randomised, placebo-controlled trial of convalescent plasma for COVID-19: analyses by neutralising antibodies homologous to recipients' variants.}, journal = {Infectious diseases (London, England)}, volume = {56}, number = {6}, pages = {423-433}, doi = {10.1080/23744235.2024.2329957}, pmid = {38513074}, issn = {2374-4243}, abstract = {INTRODUCTION: Convalescent plasma (CP) emerged as potential treatment for COVID-19 early in the pandemic. While efficacy in hospitalised patients has been lacklustre, CP may be beneficial at the first stages of disease. Despite multiple new variants emerging, no trials have involved analyses on variant-specific antibody titres of CP.<br><br>METHODS: We recruited hospitalised COVID-19 patients within 10&#x2009;days of symptom onset and, employing a double-blinded approach, randomised them to receive 200&#x2009;ml convalescent plasma with high (HCP) or low (LCP) neutralising antibody (NAb) titre against the ancestral strain (Wuhan-like variant) or placebo in 1:1:1 ratio. Primary endpoints comprised intubation, corticosteroids for symptom aggravation, and safety assessed as serious adverse events. For a preplanned ad hoc analysis, the patients were regrouped by infused CP's NAb titers to variants infecting the recipients i.e. by titres of homologous HCP (hHCP) or LCP (hLCP).<br><br>RESULTS: Of the 57 patients, 18 received HCP, 19 LCP and 20 placebo, all groups smaller than planned. No significant differences were found for primary endpoints. In ad hoc analysis, hHCPrecipients needed significantly less respiratory support, and appeared to be given corticosteroids less frequently (1/14; 7.1%) than those receiving hLCP (9/23; 39.1%) or placebo (8/20; 40%), (p&#x2009;=&#x2009;0.077).<br><br>DISCUSSION: Our double-blinded, placebo-controlled CP therapy trial remained underpowered and does not allow any firm conclusions for early-stage hospitalised COVID-19 patients. Interestingly, however, regrouping by homologous - recipients' variant-specific - CP titres suggested benefits for hHCP. We encourage similar re-analysis of ongoing/previous larger CP studies.<br><br>TRIAL REGISTRATION: ClinTrials.gov identifier: NCT0473040.}, }
@article {pmid38510311, year = {2023}, author = {Gellman, RH and Olm, MR and Terrapon, N and Enam, F and Higginbottom, SK and Sonnenburg, JL and Sonnenburg, ED}, title = {Hadza Prevotella require diet-derived microbiota-accessible carbohydrates to persist in mice.}, journal = {Cell reports}, volume = {42}, number = {11}, pages = {}, pmid = {38510311}, issn = {2211-1247}, support = {DP1 AT009892/AT/NCCIH NIH HHS/United States ; R01 DK085025/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Mice ; *Microbiota ; Diet ; *Gastrointestinal Microbiome ; Carbohydrates ; Bacteroides ; Prevotella ; }, abstract = {Industrialization has transformed the gut microbiota, reducing the prevalence of Prevotella relative to Bacteroides. Here, we isolate Bacteroides and Prevotella strains from the microbiota of Hadza hunter-gatherers in Tanzania, a population with high levels of Prevotella. We demonstrate that plant-derived microbiota-accessible carbohydrates (MACs) are required for persistence of Prevotella copri but not Bacteroides thetaiotaomicron in vivo. Differences in carbohydrate metabolism gene content, expression, and in vitro growth reveal that Hadza Prevotella strains specialize in degrading plant carbohydrates, while Hadza Bacteroides isolates use both plant and host-derived carbohydrates, a difference mirrored in Bacteroides from non-Hadza populations. When competing directly, P. copri requires plant-derived MACs to maintain colonization in the presence of B. thetaiotaomicron, as a no-MAC diet eliminates P. copri colonization. Prevotella's reliance on plant-derived MACs and Bacteroides' ability to use host mucus carbohydrates could explain the reduced prevalence of Prevotella in populations consuming a low-MAC, industrialized diet.}, }
@article {pmid38506889, year = {2024}, author = {Koskenvuo, L and Lunkka, P and Varpe, P and Hyöty, M and Satokari, R and Haapamäki, C and Lepistö, A and Sallinen, V}, title = {Morbidity After Mechanical Bowel Preparation and Oral Antibiotics Prior to Rectal Resection: The MOBILE2 Randomized Clinical Trial.}, journal = {JAMA surgery}, volume = {159}, number = {6}, pages = {606-614}, pmid = {38506889}, issn = {2168-6262}, mesh = {Humans ; Male ; Female ; Double-Blind Method ; Middle Aged ; *Surgical Wound Infection/prevention &amp; control/epidemiology ; Aged ; *Anti-Bacterial Agents/administration &amp; dosage/therapeutic use ; *Rectal Neoplasms/surgery ; Administration, Oral ; Antibiotic Prophylaxis ; Preoperative Care/methods ; Neomycin/administration &amp; dosage/therapeutic use ; Cathartics/administration &amp; dosage ; Metronidazole/administration &amp; dosage/therapeutic use ; Proctectomy/adverse effects ; Rectum/surgery ; Surgical Wound Dehiscence/prevention &amp; control/etiology ; Elective Surgical Procedures/adverse effects ; }, abstract = {IMPORTANCE: Surgical site infections (SSIs)-especially anastomotic dehiscence-are major contributors to morbidity and mortality after rectal resection. The role of mechanical and oral antibiotics bowel preparation (MOABP) in preventing complications of rectal resection is currently disputed.<br><br>OBJECTIVE: To assess whether MOABP reduces overall complications and SSIs after elective rectal resection compared with mechanical bowel preparation (MBP) plus placebo.<br><br>This multicenter, double-blind, placebo-controlled randomized clinical trial was conducted at 3 university hospitals in Finland between March 18, 2020, and October 10, 2022. Patients aged 18 years and older undergoing elective resection with primary anastomosis of a rectal tumor 15 cm or less from the anal verge on magnetic resonance imaging were eligible for inclusion. Outcomes were analyzed using a modified intention-to-treat principle, which included all patients who were randomly allocated to and underwent elective rectal resection with an anastomosis.<br><br>INTERVENTIONS: Patients were stratified according to tumor distance from the anal verge and neoadjuvant treatment given and randomized in a 1:1 ratio to receive MOABP with an oral regimen of neomycin and metronidazole (n&#x2009;=&#x2009;277) or MBP plus matching placebo tablets (n&#x2009;=&#x2009;288). All study medications were taken the day before surgery, and all patients received intravenous antibiotics approximately 30 minutes before surgery.<br><br>MAIN OUTCOMES AND MEASURES: The primary outcome was overall cumulative postoperative complications measured using the Comprehensive Complication Index. Key secondary outcomes were SSI and anastomotic dehiscence within 30 days after surgery.<br><br>RESULTS: In all, 565 patients were included in the analysis, with 288 in the MBP plus placebo group (median [IQR] age, 69 [62-74] years; 190 males [66.0%]) and 277 in the MOABP group (median [IQR] age, 70 [62-75] years; 158 males [57.0%]). Patients in the MOABP group experienced fewer overall postoperative complications (median [IQR] Comprehensive Complication Index, 0 [0-8.66] vs 8.66 [0-20.92]; Wilcoxon effect size, 0.146; P&#x2009;<&#x2009;.001), fewer SSIs (23 patients [8.3%] vs 48 patients [16.7%]; odds ratio, 0.45 [95% CI, 0.27-0.77]), and fewer anastomotic dehiscences (16 patients [5.8%] vs 39 patients [13.5%]; odds ratio, 0.39 [95% CI, 0.21-0.72]) compared with patients in the MBP plus placebo group.<br><br>CONCLUSIONS AND RELEVANCE: Findings of this randomized clinical trial indicate that MOABP reduced overall postoperative complications as well as rates of SSIs and anastomotic dehiscences in patients undergoing elective rectal resection compared with MBP plus placebo. Based on these findings, MOABP should be considered as standard treatment in patients undergoing elective rectal resection.<br><br>TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04281667.}, }
@article {pmid38504586, year = {2024}, author = {Brogna, C and Montano, L and Zanolin, ME and Bisaccia, DR and Ciammetti, G and Viduto, V and Fabrowski, M and Baig, AM and Gerlach, J and Gennaro, I and Bignardi, E and Brogna, B and Frongillo, A and Cristoni, S and Piscopo, M}, title = {A retrospective cohort study on early antibiotic use in vaccinated and unvaccinated COVID-19 patients.}, journal = {Journal of medical virology}, volume = {96}, number = {3}, pages = {e29507}, doi = {10.1002/jmv.29507}, pmid = {38504586}, issn = {1096-9071}, mesh = {Humans ; *Anti-Bacterial Agents/therapeutic use ; *COVID-19/prevention &amp; control ; Rifaximin ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; COVID-19 Vaccines ; Retrospective Studies ; Anti-Inflammatory Agents, Non-Steroidal ; Adrenal Cortex Hormones ; }, abstract = {The bacteriophage behavior of SARS-CoV-2 during the acute and post-COVID-19 phases appears to be an important factor in the development of the disease. The early use of antibiotics seems to be crucial to inhibit disease progression-to prevent viral replication in the gut microbiome, and control toxicological production from the human microbiome. To study the impact of specific antibiotics on recovery from COVID-19 and long COVID (LC) taking into account: vaccination status, comorbidities, SARS-CoV-2 wave, time of initiation of antibiotic therapy and concomitant use of corticosteroids and nonsteroidal anti-inflammatory drugs (NSAIDs). A total of 211 COVID-19 patients were included in the study: of which 59 were vaccinated with mRNA vaccines against SARS-CoV-2 while 152 were unvaccinated. Patients were enrolled in three waves: from September 2020 to October 2022, corresponding to the emergence of the pre-Delta, Delta, and Omicron variants of the SARS-CoV-2 virus. The three criteria for enrolling patients were: oropharyngeal swab positivity or fecal findings; moderate symptoms with antibiotic intake; and measurement of blood oxygen saturation during the period of illness. The use of antibiotic combinations, such as amoxicillin with clavulanic acid (875 + 125 mg tablets, every 12 h) plus rifaximin (400 mg tablets every 12 h), as first choice, as suggested from the previous data, or azithromycin (500 mg tablets every 24 h), plus rifaximin as above, allows healthcare professionals to focus on the gut microbiome and its implications in COVID-19 disease during patient care. The primary outcome measured in this study was the estimated average treatment effect, which quantified the difference in mean recovery between patients receiving antibiotics and those not receiving antibiotics at 3 and 9 days after the start of treatment. In the analysis, both vaccinated and unvaccinated groups had a median illness duration of 7 days (interquartile range [IQR] 6-9 days for each; recovery crude hazard ratio [HR] = 0.94, p = 0.700). The median illness duration for the pre-Delta and Delta waves was 8 days (IQR 7-10 days), while it was shorter, 6.5 days, for Omicron (IQR 6-8 days; recovery crude HR = 1.71, p < 0.001). These results were confirmed by multivariate analysis. Patients with comorbidities had a significantly longer disease duration: median 8 days (IQR 7-10 days) compared to 7 days (IQR 6-8 days) for those without comorbidities (crude HR = 0.75, p = 0.038), but this result was not confirmed in multivariate analysis as statistical significance was lost. Early initiation of antibiotic therapy resulted in a significantly shorter recovery time (crude HR = 4.74, p < 0.001). Concomitant use of NSAIDs did not reduce disease duration and in multivariate analysis prolonged the disease (p = 0.041). A subgroup of 42 patients receiving corticosteroids for a median of 3 days (IQR 3-6 days) had a longer recovery time (median 9 days, IQR 8-10 days) compared to others (median 7 days, IQR 6-8 days; crude HR = 0.542, p < 0.001), as confirmed also by the adjusted HR. In this study, a statistically significant reduction in recovery time was observed among patients who received early antibiotic treatment. Early initiation of antibiotics played a crucial role in maintaining higher levels of blood oxygen saturation. In addition, it is worth noting that a significant number of patients who received antibiotics in the first 3 days and for a duration of 7 days, during the acute phase did not develop LC.}, }
@article {pmid38497260, year = {2024}, author = {Singh, A and Luallen, RJ}, title = {Understanding the factors regulating host-microbiome interactions using Caenorhabditis elegans.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {379}, number = {1901}, pages = {20230059}, pmid = {38497260}, issn = {1471-2970}, support = {R35 GM146836/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Humans ; Caenorhabditis elegans/genetics ; *Microbiota ; *Gastrointestinal Microbiome ; }, abstract = {The Human Microbiome Project was a research programme that successfully identified associations between microbial species and healthy or diseased individuals. However, a major challenge identified was the absence of model systems for studying host-microbiome interactions, which would increase our capacity to uncover molecular interactions, understand organ-specificity and discover new microbiome-altering health interventions. Caenorhabditis elegans has been a pioneering model organism for over 70 years but was largely studied in the absence of a microbiome. Recently, ecological sampling of wild nematodes has uncovered a large amount of natural genetic diversity as well as a slew of associated microbiota. The field has now explored the interactions of C. elegans with its associated gut microbiome, a defined and non-random microbial community, highlighting its suitability for dissecting host-microbiome interactions. This core microbiome is being used to study the impact of host genetics, age and stressors on microbiome composition. Furthermore, single microbiome species are being used to dissect molecular interactions between microbes and the animal gut. Being amenable to health altering genetic and non-genetic interventions, C. elegans has emerged as a promising system to generate and test new hypotheses regarding host-microbiome interactions, with the potential to uncover novel paradigms relevant to other systems. This article is part of the theme issue 'Sculpting the microbiome: how host factors determine and respond to microbial colonization'.}, }
@article {pmid38491556, year = {2024}, author = {Elradi, M and Ahmed, AI and Saleh, AM and Abdel-Raouf, KMA and Berika, L and Daoud, Y and Amleh, A}, title = {Derivation of a novel antimicrobial peptide from the Red Sea Brine Pools modified to enhance its anticancer activity against U2OS cells.}, journal = {BMC biotechnology}, volume = {24}, number = {1}, pages = {14}, pmid = {38491556}, issn = {1472-6750}, mesh = {Animals ; Mice ; Humans ; Caspase 3/genetics/metabolism/pharmacology ; Survivin/genetics/metabolism/pharmacology ; Escherichia coli/metabolism ; Antimicrobial Peptides ; Cell Line, Tumor ; Indian Ocean ; Ki-67 Antigen/metabolism ; Staphylococcus aureus ; Apoptosis ; Peptides/pharmacology/metabolism ; *Antineoplastic Agents/pharmacology/chemistry ; *Anti-Infective Agents/pharmacology ; Annexins/pharmacology ; *Salts ; }, abstract = {Cancer associated drug resistance is a major cause for cancer aggravation, particularly as conventional therapies have presented limited efficiency, low specificity, resulting in long term deleterious side effects. Peptide based drugs have emerged as potential alternative cancer treatment tools due to their selectivity, ease of design and synthesis, safety profile, and low cost of manufacturing. In this study, we utilized the Red Sea metagenomics database, generated during AUC/KAUST Red Sea microbiome project, to derive a viable anticancer peptide (ACP). We generated a set of peptide hits from our library that shared similar composition to ACPs. A peptide with a homeodomain was selected, modified to improve its anticancer properties, verified to maintain high anticancer properties, and processed for further in-silico prediction of structure and function. The peptide's anticancer properties were then assessed in vitro on osteosarcoma U2OS cells, through cytotoxicity assay (MTT assay), scratch-wound healing assay, apoptosis/necrosis detection assay (Annexin/PI assay), RNA expression analysis of Caspase 3, KI67 and Survivin, and protein expression of PARP1. L929 mouse fibroblasts were also assessed for cytotoxicity treatment. In addition, the antimicrobial activity of the peptide was also examined on E coli and S. aureus, as sample representative species of the human bacterial microbiome, by examining viability, disk diffusion, morphological assessment, and hemolytic analysis. We observed a dose dependent cytotoxic response from peptide treatment of U2OS, with a higher tolerance in L929s. Wound closure was debilitated in cells exposed to the peptide, while annexin fluorescent imaging suggested peptide treatment caused apoptosis as a major mode of cell death. Caspase 3 gene expression was not altered, while KI67 and Survivin were both downregulated in peptide treated cells. Additionally, PARP-1 protein analysis showed a decrease in expression with peptide exposure. The peptide exhibited minimal antimicrobial activity on critical human microbiome species E. coli and S. aureus, with a low inhibition rate, maintenance of structural morphology and minimal hemolytic impact. These findings suggest our novel peptide displayed preliminary ACP properties against U2OS cells, through limited specificity, while triggering apoptosis as a primary mode of cell death and while having minimal impact on the microbiological species E. coli and S. aureus.}, }
@article {pmid38489954, year = {2024}, author = {Huang, Y and Zhang, R and Hong, X and Liu, S and Zhang, S and Guo, M and Shi, L and Li, Z and Liu, Y}, title = {Correlation between sarcopenia index and cognitive function in older adult women: A cross-sectional study using NHANES data.}, journal = {Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia}, volume = {122}, number = {}, pages = {73-79}, doi = {10.1016/j.jocn.2024.02.026}, pmid = {38489954}, issn = {1532-2653}, mesh = {Humans ; Female ; United States/epidemiology ; Aged ; *Sarcopenia/diagnosis/epidemiology ; Cross-Sectional Studies ; Nutrition Surveys ; Reproducibility of Results ; Cognition/physiology ; }, abstract = {OBJECTIVES: The Sarcopenia Index (SI) has the potential as a biomarker for sarcopenia, which is characterized by muscle loss. There is a clear association between sarcopenia and cognitive impairment. However, the relationship between SI and cognitive impairment is yet to be fully understood.<br><br>METHODS: We employed data extracted from the U.S. National Health and Nutrition Examination Survey (NHANES) spanning the years 1999 to 2002. Our study encompassed individuals aged 65 to 80 who possessed accessible information regarding both SI and cognitive evaluations with a GFR&#xa0;&#x2265;&#xa0;90. Cognitive function was assessed using the digit symbol substitution test (DSST). SI was calculated by serum creatinine (mg/dL)/cystatin C (mg/L)*100. Employing multivariate modeling, we estimated the connection between SI and cognitive performance. Furthermore, to enhance the reliability of our data analysis, we categorized SI using tertiles and subsequently calculated the P-value for trend.<br><br>RESULTS: After adjustment for potential confounders, we found SI was significantly and positively correlated with cognitive function scores both in older female in the American population [&#x3b2;&#xa0;=&#xa0;0.160, 95&#xa0;% confidence interval (CI) 0.050 to 0.271, P&#xa0;=&#xa0;0.00461]. Similarly, when the total cognitive function score was treated as a categorical variable according to tertiles, higher SI was related to better total cognitive function scores in females [odds ratio (OR)&#xa0;=&#xa0;3.968, 95&#xa0;% CI 1.863 to 6.073, P&#xa0;=&#xa0;0.00025] following adjustment for confounders.<br><br>CONCLUSIONS: Higher SI was correlated with a lower prevalence of cognitive impairment among older adult women with normal kidney function.}, }
@article {pmid38484733, year = {2024}, author = {Zheng, J and Zhang, XM and Tang, W and Li, Y and Wang, P and Jin, J and Luo, Z and Fang, S and Yang, S and Wei, Z and Song, K and Huang, Z and Wang, Z and Zhu, Z and Shi, N and Xiao, D and Yuan, L and Shen, H and Huang, L and Li, B}, title = {An insular cortical circuit required for itch sensation and aversion.}, journal = {Current biology : CB}, volume = {34}, number = {7}, pages = {1453-1468.e6}, doi = {10.1016/j.cub.2024.02.060}, pmid = {38484733}, issn = {1879-0445}, mesh = {Humans ; *Insular Cortex ; *Sensation/physiology ; GABAergic Neurons/metabolism ; Histamine/adverse effects/metabolism ; Pruritus/chemically induced ; }, abstract = {Itch encompasses both sensory and emotional dimensions, with the two dimensions reciprocally exacerbating each other. However, whether a shared neural circuit mechanism governs both dimensions remains elusive. Here, we report that the anterior insular cortex (AIC) is activated by both histamine-dependent and -independent itch stimuli. The activation of AIC elicits aversive emotion and exacerbates pruritogen-induced itch sensation and aversion. Mechanistically, AIC excitatory neurons project to the GABAergic neurons in the dorsal bed nucleus of the stria terminalis (dBNST). Manipulating the activity of the AIC → dBNST pathway affects both itch sensation and itch-induced aversion. Our study discovers the shared neural circuit (AIC → dBNST pathway) underlying the itch sensation and aversion, highlights the critical role of the AIC as a central hub for the itch processing, and provides a framework to understand the neural mechanisms underlying the sensation and emotion interaction.}, }
@article {pmid38484036, year = {2024}, author = {Noto Guillen, M and Li, C and Rosener, B and Mitchell, A}, title = {Antibacterial activity of nonantibiotics is orthogonal to standard antibiotics.}, journal = {Science (New York, N.Y.)}, volume = {384}, number = {6691}, pages = {93-100}, doi = {10.1126/science.adk7368}, pmid = {38484036}, issn = {1095-9203}, support = {R01 AI170722/AI/NIAID NIH HHS/United States ; R35 GM133775/GM/NIGMS NIH HHS/United States ; }, mesh = {Humans ; *Anti-Bacterial Agents/chemistry/classification/pharmacology ; Escherichia coli/drug effects/genetics ; Inhibitory Concentration 50 ; Microbial Sensitivity Tests ; *Microbiota/drug effects/genetics ; }, abstract = {Numerous nonantibiotic drugs have potent antibacterial activity and can adversely affect the human microbiome. The mechanistic underpinning of this toxicity remains largely unknown. We investigated the antibacterial activity of 200 drugs using genetic screens with thousands of barcoded Escherichia coli knockouts. We analyzed 2 million gene-drug interactions underlying drug-specific toxicity. Network-based analysis of drug-drug similarities revealed that antibiotics clustered into modules that are consistent with the mode of action of their established classes, whereas nonantibiotics remained unconnected. Half of the nonantibiotics clustered into separate modules, potentially revealing shared and unexploited targets for new antimicrobials. Analysis of efflux systems revealed that they widely affect antibiotics and nonantibiotics alike, suggesting that the impact of nonantibiotics on antibiotic cross-resistance should be investigated closely in vivo.}, }
@article {pmid38479397, year = {2024}, author = {Zhou, X and Shen, X and Johnson, JS and Spakowicz, DJ and Agnello, M and Zhou, W and Avina, M and Honkala, A and Chleilat, F and Chen, SJ and Cha, K and Leopold, S and Zhu, C and Chen, L and Lyu, L and Hornburg, D and Wu, S and Zhang, X and Jiang, C and Jiang, L and Jiang, L and Jian, R and Brooks, AW and Wang, M and Contrepois, K and Gao, P and Rose, SMS and Tran, TDB and Nguyen, H and Celli, A and Hong, BY and Bautista, EJ and Dorsett, Y and Kavathas, PB and Zhou, Y and Sodergren, E and Weinstock, GM and Snyder, MP}, title = {Longitudinal profiling of the microbiome at four body sites reveals core stability and individualized dynamics during health and disease.}, journal = {Cell host &amp; microbe}, volume = {32}, number = {4}, pages = {506-526.e9}, pmid = {38479397}, issn = {1934-6069}, support = {RM1 HG007735/HG/NHGRI NIH HHS/United States ; U54 DE023789/DE/NIDCR NIH HHS/United States ; K08 ES028825/ES/NIEHS NIH HHS/United States ; P30 AG059307/AG/NIA NIH HHS/United States ; F32 DK126287/DK/NIDDK NIH HHS/United States ; R01 DK110186/DK/NIDDK NIH HHS/United States ; R01 AT010232/AT/NCCIH NIH HHS/United States ; UL1 TR001085/TR/NCATS NIH HHS/United States ; P30 CA016058/CA/NCI NIH HHS/United States ; K01 AG070310/AG/NIA NIH HHS/United States ; P30 DK116074/DK/NIDDK NIH HHS/United States ; U54 DK102556/DK/NIDDK NIH HHS/United States ; UL1 TR003142/TR/NCATS NIH HHS/United States ; }, mesh = {Humans ; *Core Stability ; *Microbiota ; Skin/microbiology ; Host Microbial Interactions ; Biomarkers ; }, abstract = {To understand the dynamic interplay between the human microbiome and host during health and disease, we analyzed the microbial composition, temporal dynamics, and associations with host multi-omics, immune, and clinical markers of microbiomes from four body sites in 86 participants over 6 years. We found that microbiome stability and individuality are body-site specific and heavily influenced by the host. The stool and oral microbiome are more stable than the skin and nasal microbiomes, possibly due to their interaction with the host and environment. We identify individual-specific and commonly shared bacterial taxa, with individualized taxa showing greater stability. Interestingly, microbiome dynamics correlate across body sites, suggesting systemic dynamics influenced by host-microbial-environment interactions. Notably, insulin-resistant individuals show altered microbial stability and associations among microbiome, molecular markers, and clinical features, suggesting their disrupted interaction in metabolic disease. Our study offers comprehensive views of multi-site microbial dynamics and their relationship with host health and disease.}, }
@article {pmid38477427, year = {2024}, author = {Zhang, J and Qi, H and Li, M and Wang, Z and Jia, X and Sun, T and Du, S and Su, C and Zhi, M and Du, W and Ouyang, Y and Wang, P and Huang, F and Jiang, H and Li, L and Bai, J and Wei, Y and Zhang, X and Wang, H and Zhang, B and Feng, Q}, title = {Diet Mediate the Impact of Host Habitat on Gut Microbiome and Influence Clinical Indexes by Modulating Gut Microbes and Serum Metabolites.}, journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)}, volume = {11}, number = {19}, pages = {e2310068}, pmid = {38477427}, issn = {2198-3844}, support = {ZR202102230369//Excellent Scientist Foundation of Shandong Province/ ; P30 AG066615/AG/NIA NIH HHS/United States ; R01 HD038700/HD/NICHD NIH HHS/United States ; 2021SFGC0502//Major Innovation Projects in Shandong Province/ ; P30-DK056350/DK/NIDDK NIH HHS/United States ; R01 DK104371/DK/NIDDK NIH HHS/United States ; R01 AG065357/AG/NIA NIH HHS/United States ; R01-DK104371/DK/NIDDK NIH HHS/United States ; R01-HD30880//Eunice Kennedy Shriver National Institute of Child Health and Human Development/ ; R01 HL108427/HL/NHLBI NIH HHS/United States ; D43 TW009077/TW/FIC NIH HHS/United States ; 82071122//National Natural Science Foundation of China/ ; 2021YFE0114200//Ministry of Science and Technology of the People's Republic of China/ ; R01-HD38700//Eunice Kennedy Shriver National Institute of Child Health and Human Development/ ; P30 DK056350/DK/NIDDK NIH HHS/United States ; //National Young Scientist Project Foundation of China (2019)/ ; R24 HD050924/HD/NICHD NIH HHS/United States ; 2021GXRC021//Oral Microbiome Innovation Team of Jinan City/ ; //Program of Taishan Young from Shandong Province/ ; R01 HD030880/HD/NICHD NIH HHS/United States ; 2020KJK001//Oral Microbiome Innovation Team of Shandong Province/ ; D43 TW007709/TW/FIC NIH HHS/United States ; }, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Diet/methods ; China ; Male ; Female ; Metabolome/physiology ; Adult ; Middle Aged ; Ecosystem ; }, abstract = {The impact of external factors on the human gut microbiota and how gut microbes contribute to human health is an intriguing question. Here, the gut microbiome of 3,224 individuals (496 with serum metabolome) with 109 variables is studied. Multiple analyses reveal that geographic factors explain the greatest variance of the gut microbiome and the similarity of individuals' gut microbiome is negatively correlated with their geographic distance. Main food components are the most important factors that mediate the impact of host habitats on the gut microbiome. Diet and gut microbes collaboratively contribute to the variation of serum metabolites, and correlate to the increase or decrease of certain clinical indexes. Specifically, systolic blood pressure is lowered by vegetable oil through increasing the abundance of Blautia and reducing the serum level of 1-palmitoyl-2-palmitoleoyl-GPC (16:0/16:1), but it is reduced by fruit intake through increasing the serum level of Blautia improved threonate. Besides, aging-related clinical indexes are also closely correlated with the variation of gut microbes and serum metabolites. In this study, the linkages of geographic locations, diet, the gut microbiome, serum metabolites, and physiological indexes in a Chinese population are characterized. It is proved again that gut microbes and their metabolites are important media for external factors to affect human health.}, }
@article {pmid38474213, year = {2024}, author = {Hong, BY and Driscoll, M and Gratalo, D and Jarvie, T and Weinstock, GM}, title = {Improved DNA Extraction and Amplification Strategy for 16S rRNA Gene Amplicon-Based Microbiome Studies.}, journal = {International journal of molecular sciences}, volume = {25}, number = {5}, pages = {}, pmid = {38474213}, issn = {1422-0067}, mesh = {Humans ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA/methods ; Genes, rRNA ; Reproducibility of Results ; DNA, Bacterial/genetics ; *Microbiota/genetics ; Bacteria/genetics ; High-Throughput Nucleotide Sequencing/methods ; }, abstract = {Next-generation sequencing technology has driven the rapid advancement of human microbiome studies by enabling community-level sequence profiling of microbiomes. Although all microbiome sequencing methods depend on recovering the DNA from a sample as a first critical step, lysis methods can be a major determinant of microbiome profile bias. Gentle enzyme-based DNA preparation methods preserve DNA quality but can bias the results by failing to open difficult-to-lyse bacteria. Mechanical methods like bead beating can also bias DNA recovery because the mechanical energy required to break tougher cell walls may shear the DNA of the more easily lysed microbes, and shearing can vary depending on the time and intensity of beating, influencing reproducibility. We introduce a non-mechanical, non-enzymatic, novel rapid microbial DNA extraction procedure suitable for 16S rRNA gene-based microbiome profiling applications that eliminates bead beating. The simultaneous application of alkaline, heat, and detergent ('Rapid' protocol) to milligram quantity samples provided consistent representation across the population of difficult and easily lysed bacteria equal to or better than existing protocols, producing sufficient high-quality DNA for full-length 16S rRNA gene PCR. The novel 'Rapid' method was evaluated using mock bacterial communities containing both difficult and easily lysed bacteria. Human fecal sample testing compared the novel Rapid method with a standard Human Microbiome Project (HMP) protocol for samples from lung cancer patients and controls. DNA recovered from both methods was analyzed using 16S rRNA gene sequencing of the V1V3 and V4 regions on the Illumina platform and the V1V9 region on the PacBio platform. Our findings indicate that the 'Rapid' protocol consistently yielded higher levels of Firmicutes species, which reflected the profile of the bacterial community structure more accurately, which was confirmed by mock community evaluation. The novel 'Rapid' DNA lysis protocol reduces population bias common to bead beating and enzymatic lysis methods, presenting opportunities for improved microbial community profiling, combined with the reduction in sample input to 10 milligrams or less, and it enables rapid transfer and simultaneous lysis of 96 samples in a standard plate format. This results in a 20-fold reduction in sample handling time and an overall 2-fold time advantage when compared to widely used commercial methods. We conclude that the novel 'Rapid' DNA extraction protocol offers a reliable alternative for preparing fecal specimens for 16S rRNA gene amplicon sequencing.}, }
@article {pmid38472421, year = {2024}, author = {Cai, J and Lin, K and Luo, T and Weng, J and Liu, H and Yuan, Z and Wan, Z and Han, J and Lin, J and Liu, X and Wang, X and Huang, M and Luo, Y and Yu, H}, title = {Neoadjuvant chemotherapy is noninferior to chemoradiotherapy for early-onset locally advanced rectal cancer in the FOWARC trial.}, journal = {British journal of cancer}, volume = {130}, number = {9}, pages = {1434-1440}, pmid = {38472421}, issn = {1532-1827}, support = {No. 81972245, YL; No. 82173067, YL; No. 81902877, HY; No. 82272965, HY//National Natural Science Foundation of China (National Science Foundation of China)/ ; No. 2022A1515012656, HY; No.2021A1515010134, MH;No.2020A1515010036, XL//Natural Science Foundation of Guangdong Province (Guangdong Natural Science Foundation)/ ; }, mesh = {Humans ; *Rectal Neoplasms/therapy/pathology ; *Neoadjuvant Therapy/methods ; Male ; Female ; Middle Aged ; Aged ; Chemoradiotherapy/methods ; Adult ; Treatment Outcome ; Age of Onset ; }, abstract = {BACKGROUND: The early-onset rectal cancer with rapidly increasing incidence is considered to have distinct clinicopathological and molecular profiles with high-risk features. This leads to challenges in developing specific treatment strategies for early-onset rectal cancer patients and questions of whether early-onset locally advanced rectal cancer (LARC) needs aggressive neoadjuvant treatment.<br><br>METHODS: In this post hoc analysis of FOWARC trial, we investigated the role of preoperative radiation in early-onset LARC by comparing the clinicopathological profiles and short-term and long-term outcomes between the early-onset and late-onset LARCs.<br><br>RESULTS: We revealed an inter-tumor heterogeneity of clinical profiles and treatment outcomes between the early-onset and late-onset LARCs. The high-risk features were more prevalent in early-onset LARC. The neoadjuvant radiation brought less benefits of tumor response and more risk of complications in early-onset group (pCR: OR&#x2009;=&#x2009;3.75, 95% CI&#x2009;=&#x2009;1.37-10.27; complications: HR&#x2009;=&#x2009;11.35, 95% CI&#x2009;=&#x2009;1.46-88.31) compared with late-onset group (pCR: OR&#x2009;=&#x2009;5.33, 95% CI&#x2009;=&#x2009;1.83-15.58; complications: HR&#x2009;=&#x2009;5.80, 95% CI&#x2009;=&#x2009;2.32-14.49). Furthermore, the addition of radiation to neoadjuvant chemotherapy didn't improve long-term OS (HR&#x2009;=&#x2009;1.37, 95% CI&#x2009;=&#x2009;0.49-3.87) and DFS (HR&#x2009;=&#x2009;1.05, 95% CI&#x2009;=&#x2009;0.58-1.90) for early-onset patients.<br><br>CONCLUSION: Preoperative radiation plus chemotherapy may not be superior to the chemotherapy alone in the early-onset LARC. Our findings provide insight into the treatment of early-onset LARC by interrogating the aggressive treatment and alternative regimens.}, }
@article {pmid38471667, year = {2024}, author = {Ghelfenstein-Ferreira, T and Serris, A and Salmona, M and Lanternier, F and Alanio, A}, title = {Revealing the hidden interplay: The unexplored relationship between fungi and viruses beyond HIV, SARS-CoV-2, and influenza.}, journal = {Medical mycology}, volume = {62}, number = {4}, pages = {}, doi = {10.1093/mmy/myae021}, pmid = {38471667}, issn = {1460-2709}, mesh = {Humans ; SARS-CoV-2 ; *Influenza, Human/complications ; *COVID-19/complications/veterinary ; Ecosystem ; *Viruses ; Fungi ; *Pulmonary Aspergillosis/veterinary ; *HIV Infections/complications/veterinary ; }, abstract = {The complex interaction between viruses and fungi has profound implications, especially given the significant impact of these microorganisms on human health. While well-known examples such as HIV, influenza, and SARS-CoV-2 are recognized as risk factors for invasive fungal diseases, the relationship between viruses and fungi remains largely underexplored outside of these cases. Fungi and viruses can engage in symbiotic or synergistic interactions. Remarkably, some viruses, known as mycoviruses, can directly infect fungi, may influencing their phenotype and potentially their virulence. In addition, viruses and fungi can coexist within the human microbiome, a complex ecosystem of microorganisms. Under certain conditions, viral infection might predispose the host to an invasive fungal infection, as observed with influenza-associated pulmonary aspergillosis or COVID-19 associated pulmonary aspergillosis. We aim in this review to highlight potential connections between fungi and viruses (CMV and other herpesviruses, HTLV-1 and respiratory viruses), excluding SARS-CoV-2 and influenza.}, }
@article {pmid38467837, year = {2024}, author = {Bhosle, A and Bae, S and Zhang, Y and Chun, E and Avila-Pacheco, J and Geistlinger, L and Pishchany, G and Glickman, JN and Michaud, M and Waldron, L and Clish, CB and Xavier, RJ and Vlamakis, H and Franzosa, EA and Garrett, WS and Huttenhower, C}, title = {Integrated annotation prioritizes metabolites with bioactivity in inflammatory bowel disease.}, journal = {Molecular systems biology}, volume = {20}, number = {4}, pages = {338-361}, pmid = {38467837}, issn = {1744-4292}, support = {P30 DK040561/DK/NIDDK NIH HHS/United States ; P30 DK043351/DK/NIDDK NIH HHS/United States ; R01 CA230551/CA/NCI NIH HHS/United States ; R24 DK110499/DK/NIDDK NIH HHS/United States ; }, mesh = {Humans ; Animals ; Mice ; *Inflammatory Bowel Diseases/drug therapy/metabolism ; *Colitis ; Metabolome ; Bile Acids and Salts ; }, abstract = {Microbial biochemistry is central to the pathophysiology of inflammatory bowel diseases (IBD). Improved knowledge of microbial metabolites and their immunomodulatory roles is thus necessary for diagnosis and management. Here, we systematically analyzed the chemical, ecological, and epidemiological properties of ~82k metabolic features in 546 Integrative Human Microbiome Project (iHMP/HMP2) metabolomes, using a newly developed methodology for bioactive compound prioritization from microbial communities. This suggested >1000 metabolic features as potentially bioactive in IBD and associated ~43% of prevalent, unannotated features with at least one well-characterized metabolite, thereby providing initial information for further characterization of a significant portion of the fecal metabolome. Prioritized features included known IBD-linked chemical families such as bile acids and short-chain fatty acids, and less-explored bilirubin, polyamine, and vitamin derivatives, and other microbial products. One of these, nicotinamide riboside, reduced colitis scores in DSS-treated mice. The method, MACARRoN, is generalizable with the potential to improve microbial community characterization and provide therapeutic candidates.}, }
@article {pmid38466102, year = {2024}, author = {Cheng, G and Westerholm, M and Schnürer, A}, title = {Complete genome sequence of Citroniella saccharovorans DSM 29873, isolated from human fecal sample.}, journal = {Microbiology resource announcements}, volume = {13}, number = {4}, pages = {e0001524}, pmid = {38466102}, issn = {2576-098X}, support = {2018-01341//Svenska Forskningsr&#xe5;det Formas (Formas)/ ; 948138//EC | European Research Council (ERC)/ ; 2018-01341//Svenska Forskningsr&#xe5;det Formas (Formas)/ ; }, abstract = {A complete genome was recovered from Citroniella saccharovorans, strain DSM 29873, using Oxford Nanopore Technologies. The genome assembly contains 1,413,868 bp with 30.23% G+C content. The species belongs to the family Peptoniphilaceae and, as of yet, is the only cultivated representative of the genus Citroniella.}, }
@article {pmid38465728, year = {2024}, author = {Michán-Doña, A and Vázquez-Borrego, MC and Michán, C}, title = {Are there any completely sterile organs or tissues in the human body? Is there any sacred place?.}, journal = {Microbial biotechnology}, volume = {17}, number = {3}, pages = {e14442}, pmid = {38465728}, issn = {1751-7915}, support = {PRYES223170ARJO//Fundaci&#xf3;n Cient&#xed;fica Asociaci&#xf3;n Espa&#xf1;ola Contra el C&#xe1;ncer/ ; PI22/01213//Instituto de Salud Carlos III/ ; }, mesh = {Humans ; *Human Body ; Sequence Analysis, DNA ; *Infertility ; DNA, Ribosomal/genetics ; RNA/genetics ; RNA, Ribosomal, 16S/genetics ; }, abstract = {The human microbiome comprises an ample set of organisms that inhabit and interact within the human body, contributing both positively and negatively to our health. In recent years, several research groups have described the presence of microorganisms in organs or tissues traditionally considered as 'sterile' under healthy and pathological conditions. In this sense, microorganisms have been detected in several types of cancer, including those in 'sterile' organs. But how can the presence of microorganisms be detected? In most studies, 16S and internal transcribed spacer (ITS) ribosomal DNA (rDNA) sequencing has led to the identification of prokaryotes and fungi. However, a major limitation of this technique is that it cannot distinguish between living and dead organisms. RNA-based methods have been proposed to overcome this limitation, as the shorter half-life of the RNA would identify only the transcriptionally active microorganisms, although perhaps not all the viable ones. In this sense, metaproteomic techniques or the search for molecular metabolic signatures could be interesting alternatives for the identification of living microorganisms. In summary, new technological advances are challenging the notion of 'sterile' organs in our body. However, to date, evidence for a structured living microbiome in most of these organs is scarce or non-existent. The implementation of new technological approaches will be necessary to fully understand the importance of the microbiome in these organs, which could pave the way for the development of a wide range of new therapeutic strategies.}, }
@article {pmid38464031, year = {2024}, author = {Zolfo, M and Silverj, A and Blanco-Míguez, A and Manghi, P and Rota-Stabelli, O and Heidrich, V and Jensen, J and Maharjan, S and Franzosa, E and Menni, C and Visconti, A and Pinto, F and Ciciani, M and Huttenhower, C and Cereseto, A and Asnicar, F and Kitano, H and Yamada, T and Segata, N}, title = {Discovering and exploring the hidden diversity of human gut viruses using highly enriched virome samples.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {38464031}, issn = {2692-8205}, support = {R01 CA230551/CA/NCI NIH HHS/United States ; U01 CA230551/CA/NCI NIH HHS/United States ; }, abstract = {Viruses are an abundant and crucial component of the human microbiome, but accurately discovering them via metagenomics is still challenging. Currently, the available viral reference genomes poorly represent the diversity in microbiome samples, and expanding such a set of viral references is difficult. As a result, many viruses are still undetectable through metagenomics even when considering the power of de novo metagenomic assembly and binning, as viruses lack universal markers. Here, we describe a novel approach to catalog new viral members of the human gut microbiome and show how the resulting resource improves metagenomic analyses. We retrieved >3,000 viral-like particles (VLP) enriched metagenomic samples (viromes), evaluated the efficiency of the enrichment in each sample to leverage the viromes of highest purity, and applied multiple analysis steps involving assembly and comparison with hundreds of thousands of metagenome-assembled genomes to discover new viral genomes. We reported over 162,000 viral sequences passing quality control from thousands of gut metagenomes and viromes. The great majority of the retrieved viral sequences (~94.4%) were of unknown origin, most had a CRISPR spacer matching host bacteria, and four of them could be detected in >50% of a set of 18,756 gut metagenomes we surveyed. We included the obtained collection of sequences in a new MetaPhlAn 4.1 release, which can quantify reads within a metagenome matching the known and newly uncovered viral diversity. Additionally, we released the viral database for further virome and metagenomic studies of the human microbiome.}, }
@article {pmid38460430, year = {2024}, author = {Karisola, P and Nikkola, V and Joronen, H and Ylianttila, L and Grönroos, M and Partonen, T and Snellman, E and Alenius, H}, title = {Narrow-band UVB radiation triggers diverse changes in the gene expression and induces the accumulation of M1 macrophages in human skin.}, journal = {Journal of photochemistry and photobiology. B, Biology}, volume = {253}, number = {}, pages = {112887}, doi = {10.1016/j.jphotobiol.2024.112887}, pmid = {38460430}, issn = {1873-2682}, mesh = {Female ; Humans ; *Proteasome Endopeptidase Complex/metabolism ; *Skin/radiation effects ; Ultraviolet Rays ; Erythema/etiology ; Macrophages ; Gene Expression ; }, abstract = {BACKGROUND: The underlying molecular mechanisms that determine the biological effects of UVB radiation exposure on human skin are still only partially comprehended.<br><br>OBJECTIVES: Our goal is to examine the human skin transcriptome and related molecular mechanisms following a single exposure to UVB in the morning versus evening.<br><br>METHODS: We exposed 20 volunteer females to four-fold standard erythema doses (SED4) of narrow-band UVB (309-313&#xa0;nm) in the morning or evening and studied skin transcriptome 24&#xa0;h after the exposure. We performed enrichment analyses of gene pathways, predicted changes in skin cell composition using cellular deconvolution, and correlated cell proportions with gene expression.<br><br>RESULTS: In the skin transcriptome, UVB exposure yielded 1384 differentially expressed genes (DEGs) in the morning and 1295 DEGs in the evening, of which the most statistically significant DEGs enhanced proteasome and spliceosome pathways. Unexposed control samples showed difference by 321 DEGs in the morning vs evening, which was related to differences in genes associated with the circadian rhythm. After the UVB exposure, the fraction of proinflammatory M1 macrophages was significantly increased at both timepoints, and this increase was positively correlated with pathways on Myc targets and mTORC1 signaling. In the evening, the skin clinical erythema was more severe and had stronger positive correlation with the number of M1 macrophages than in the morning after UVB exposure. The fractions of myeloid and plasmacytoid dendritic cells and CD8 T cells were significantly decreased in the morning but not in the evening.<br><br>CONCLUSIONS: NB-UVB-exposure causes changes in skin transcriptome, inhibiting cell division, and promoting proteasome activity and repair responses, both in the morning and in the evening. Inflammatory M1 macrophages may drive the UV-induced skin responses by exacerbating inflammation and erythema. These findings highlight how the same UVB exposure influences skin responses differently in morning versus evening and presents a possible explanation to the differences in gene expression in the skin after UVB irradiation at these two timepoints.}, }
@article {pmid38455087, year = {2024}, author = {Reid, G}, title = {A value chain to improve human, animal and insect health in developing countries.}, journal = {Microbiome research reports}, volume = {3}, number = {1}, pages = {10}, pmid = {38455087}, issn = {2771-5965}, }
@article {pmid38452522, year = {2024}, author = {Jones, JM and Reinke, SN and Mousavi-Derazmahalleh, M and Garssen, J and Jenmalm, MC and Srinivasjois, R and Silva, D and Keelan, J and Prescott, SL and Palmer, DJ and Christophersen, CT}, title = {Maternal prebiotic supplementation during pregnancy and lactation modifies the microbiome and short chain fatty acid profile of both mother and infant.}, journal = {Clinical nutrition (Edinburgh, Scotland)}, volume = {43}, number = {4}, pages = {969-980}, doi = {10.1016/j.clnu.2024.02.030}, pmid = {38452522}, issn = {1532-1983}, mesh = {Female ; Humans ; Infant ; Pregnancy ; Dietary Supplements ; Fatty Acids, Volatile/metabolism ; Lactation ; *Microbiota ; Mothers ; Oligosaccharides ; Powders ; *Prebiotics ; RNA, Ribosomal, 16S ; Infant, Newborn ; }, abstract = {BACKGROUND &amp; AIMS: Improving maternal gut health in pregnancy and lactation is a potential strategy to improve immune and metabolic health in offspring and curtail the rising rates of inflammatory diseases linked to alterations in gut microbiota. Here, we investigate the effects of a maternal prebiotic supplement (galacto-oligosaccharides and fructo-oligosaccharides), ingested daily from <21 weeks' gestation to six months' post-partum, in a double-blinded, randomised placebo-controlled trial.<br><br>METHODS: Stool samples were collected at multiple timepoints from 74 mother-infant pairs as part of a larger, double-blinded, randomised controlled allergy intervention trial. The participants were randomised to one of two groups; with one group receiving 14.2&#xa0;g per day of prebiotic powder (galacto-oligosaccharides GOS and fructo-oligosaccharides FOS in ratio 9:1), and the other receiving a placebo powder consisting of 8.7&#xa0;g per day of maltodextrin. The faecal microbiota of both mother and infants were assessed based on the analysis of bacterial 16S rRNA gene (V4 region) sequences, and short chain fatty acid (SCFA) concentrations in stool.<br><br>RESULTS: Significant differences in the maternal microbiota profiles between baseline and either 28-weeks' or 36-weeks' gestation were found in the prebiotic supplemented women. Infant microbial beta-diversity also significantly differed between prebiotic and placebo groups at 12-months of age. Supplementation was associated with increased abundance of commensal Bifidobacteria in the maternal microbiota, and a reduction in the abundance of Negativicutes in both maternal and infant microbiota. There were also changes in SCFA concentrations with maternal prebiotics supplementation, including significant differences in acetic acid concentration between intervention and control groups from 20 to 28-weeks' gestation.<br><br>CONCLUSION: Maternal prebiotic supplementation of 14.2&#xa0;g per day GOS/FOS was found to favourably modify both the maternal and the developing infant gut microbiome. These results build on our understanding of the importance of maternal diet during pregnancy, and indicate that it is possible to intervene and modify the development of the infant microbiome by dietary modulation of the maternal gut microbiome.}, }
@article {pmid38452399, year = {2024}, author = {Lucchetti, M and Aina, KO and Grandmougin, L and Jäger, C and Pérez Escriva, P and Letellier, E and Mosig, AS and Wilmes, P}, title = {An Organ-on-Chip Platform for Simulating Drug Metabolism Along the Gut-Liver Axis.}, journal = {Advanced healthcare materials}, volume = {13}, number = {20}, pages = {e2303943}, doi = {10.1002/adhm.202303943}, pmid = {38452399}, issn = {2192-2659}, support = {P500PB_214405//Schweizerischer Nationalfonds zur F&#xf6;rderung der Wissenschaftlichen Forschung/ ; CORE/C20/BM/14591557//Fonds National de la Recherche Luxembourg and Fondation Cancer/ ; 390713860//Deutsche Forschungsgemeinschaft/ ; 031 L0247A//Bundesministerium f&#xfc;r Bildung und Forschung/ ; 812954//H2020 Marie Sk&#x142;odowska-Curie Actions/ ; }, mesh = {Humans ; *Irinotecan/pharmacokinetics ; *Liver/metabolism ; *Gastrointestinal Microbiome/physiology ; Lab-On-A-Chip Devices ; Tandem Mass Spectrometry/methods ; Chromatography, Liquid/methods ; }, abstract = {The human microbiome significantly influences drug metabolism through the gut-liver axis, leading to modified drug responses and potential toxicity. Due to the complex nature of the human gut environment, the understanding of microbiome-driven impacts on these processes is limited. To address this, a multiorgan-on-a-chip (MOoC) platform that combines the human microbial-crosstalk (HuMiX) gut-on-chip (GoC) and the Dynamic42 liver-on-chip (LoC), mimicking the bidirectional interconnection between the gut and liver known as the gut-liver axis, is introduced. This platform supports the viability and functionality of intestinal and liver cells. In a proof-of-concept study, the metabolism of irinotecan, a widely used colorectal cancer drug, is imitated within the MOoC. Utilizing liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS), irinotecan metabolites are tracked, confirming the platform's ability to represent drug metabolism along the gut-liver axis. Further, using the authors' gut-liver platform, it is shown that the colorectal cancer-associated gut bacterium, Escherichia coli, modifies irinotecan metabolism through the transformation of its inactive metabolite SN-38G into its toxic metabolite SN-38. This platform serves as a robust tool for investigating the intricate interplay between gut microbes and pharmaceuticals, offering a representative alternative to animal models and providing novel drug development strategies.}, }
@article {pmid38450162, year = {2024}, author = {Bragazzi, NL and Woldegerima, WA and Siri, A}, title = {Economic microbiology: exploring microbes as agents in economic systems.}, journal = {Frontiers in microbiology}, volume = {15}, number = {}, pages = {1305148}, pmid = {38450162}, issn = {1664-302X}, abstract = {Microbial communities exhibit striking parallels with economic markets, resembling intricate ecosystems where microorganisms engage in resource exchange akin to human market transactions. This dynamic network of resource swapping mirrors economic trade in human markets, with microbes specializing in metabolic functions much like businesses specializing in goods and services. Cooperation and competition are central dynamics in microbial communities, with alliances forming for mutual benefit and species vying for dominance, similar to businesses seeking market share. The human microbiome, comprising trillions of microorganisms within and on our bodies, is not only a marker of socioeconomic status but also a critical factor contributing to persistent health inequalities. Social and economic factors shape the composition of the gut microbiota, impacting healthcare access and quality of life. Moreover, these microbes exert indirect influence over human decisions by affecting neurotransmitter production, influencing mood, behavior, and choices related to diet and emotions. Human activities significantly impact microbial communities, from dietary choices and antibiotic use to environmental changes, disrupting these ecosystems. Beyond their natural roles, humans harness microbial communities for various applications, manipulating their interactions and resource exchanges to achieve specific goals in fields like medicine, agriculture, and environmental science. In conclusion, the concept of microbial communities as biological markets offers valuable insights into their intricate functioning and adaptability. It underscores the profound interplay between microbial ecosystems and human health and behavior, with far-reaching implications for multiple disciplines. To paraphrase Alfred Marshall, "the Mecca of the economist lies in economic microbiology."}, }
@article {pmid38441984, year = {2024}, author = {Greenzaid, JD and Chan, LJ and Chandani, BM and Kiritsis, NR and Feldman, SR}, title = {Microbiome modulators for atopic eczema: a systematic review of experimental and investigational therapeutics.}, journal = {Expert opinion on investigational drugs}, volume = {33}, number = {4}, pages = {415-430}, doi = {10.1080/13543784.2024.2326625}, pmid = {38441984}, issn = {1744-7658}, mesh = {*Dermatitis, Atopic/drug therapy/microbiology ; Humans ; *Probiotics/administration &amp; dosage/pharmacology ; Animals ; *Microbiota ; *Severity of Illness Index ; *Biological Products/pharmacology/administration &amp; dosage ; Staphylococcus aureus/isolation &amp; purification/drug effects ; Skin/microbiology ; Gastrointestinal Microbiome ; Th2 Cells/immunology ; Antibodies, Monoclonal ; }, abstract = {INTRODUCTION: Atopic dermatitis (AD) is a common inflammatory cutaneous disease that arises due to dysregulation of the Th2 immune response, impaired skin barrier integrity, and dysbiosis of the skin and gut microbiota. An abundance of Staphylococcus aureus biofilms in AD lesions increases the Th2 immune response, and gut bacteria release breakdown products such as Short Chain Fatty Acids that regulate the systemic immune response.<br><br>AREAS COVERED: We aim to evaluate therapies that modulate the microbiome in humans and discuss the clinical implications of these treatments. We performed a review of the literature in which 2,673 records were screened, and describe the findings of 108 studies that were included after full-text review. All included studies discussed the effects of therapies on the human microbiome and AD severity. Oral probiotics, topical probiotics, biologics, and investigational therapies were included in our analysis.<br><br>EXPERT OPINION: Oral probiotics demonstrate mixed efficacy at relieving AD symptoms. Topical probiotics reduce S. aureus abundance in AD lesional skin, yet for moderate-severe disease, these therapies may not reduce AD severity scores to the standard of biologics. Dupilumab and tralokinumab target key inflammatory pathways in AD and modulate the skin microbiome, further improving disease severity.}, }
@article {pmid38441977, year = {2024}, author = {Chen, H and Huang, S and Zhao, Y and Sun, R and Wang, J and Yao, S and Huang, J and Yu, Z}, title = {Metagenomic analysis of the intestinal microbiome reveals the potential mechanism involved in Bacillus amyloliquefaciens in treating schistosomiasis japonica in mice.}, journal = {Microbiology spectrum}, volume = {12}, number = {4}, pages = {e0373523}, pmid = {38441977}, issn = {2165-0497}, support = {32300051//MOST | National Natural Science Foundation of China (NSFC)/ ; 32170071//MOST | National Natural Science Foundation of China (NSFC)/ ; 82102428//MOST | National Natural Science Foundation of China (NSFC)/ ; 2022JJ40663//HSTD | Natural Science Foundation of Hunan Province ()/ ; }, mesh = {Animals ; Mice ; *Schistosomiasis japonica/drug therapy ; *Gastrointestinal Microbiome ; *Bacillus amyloliquefaciens ; Urease ; *Schistosoma japonicum/genetics ; Bacteria/genetics ; }, abstract = {UNLABELLED: Schistosomiasis japonica is one of the neglected tropical diseases characterized by chronic hepatic, intestinal granulomatous inflammation and fibrosis, as well as dysbiosis of intestinal microbiome. Previously, the probiotic Bacillus amyloliquefaciens has been shown to alleviate the pathological injuries in mice infected with Schistosoma japonicum by improving the disturbance of the intestinal microbiota. However, the underlying mechanisms involved in this process remain unclear. In this study, metagenomics sequencing and functional analysis were employed to investigate the differential changes in taxonomic composition and functional genes of the intestinal microbiome in S. japonicum-infected mice treated with B. amyloliquefaciens. The results revealed that intervention with B. amyloliquefaciens altered the taxonomic composition of the intestinal microbiota at the species level in infected mice and significantly increased the abundance of beneficial bacteria. Moreover, the abundance of predicted genes in the intestinal microbiome was also significantly changed, and the abundance of xfp/xpk and genes translated to urease was significantly restored. Further analysis showed that Limosilactobacillus reuteri was positively correlated with several KEGG Orthology (KO) genes and metabolic reactions, which might play important roles in alleviating the pathological symptoms caused by S. japonicum infection, indicating that it has the potential to function as another effective therapeutic agent for schistosomiasis. These data suggested that treatment of murine schistosomiasis japonica by B. amyloliquefaciens might be induced by alterations in the taxonomic composition and functional gene of the intestinal microbiome in mice. We hope this study will provide adjuvant strategies and methods for the early prevention and treatment of schistosomiasis japonica.<br><br>IMPORTANCE: Targeted interventions of probiotics on gut microbiome were used to explore the mechanism of alleviating schistosomiasis japonica. Through metagenomic analysis, there were significant changes in the composition of gut microbiota in mice infected with Schistosoma japonicum and significant increase in the abundance of beneficial bacteria after the intervention of Bacillus amyloliquefaciens. At the same time, the abundance of functional genes was found to change significantly. The abundance of genes related to urease metabolism and xfp/xpk related to D-erythrose 4-phosphate production was significantly restored, highlighting the importance of Limosilactobacillus reuteri in the recovery and abundance of predicted genes of the gut microbiome. These results indicated potential regulatory mechanism between the gene function of gut microbiome and host immune response. Our research lays the foundation for elucidating the regulatory mechanism of probiotic intervention in alleviating schistosomiasis japonica, and provides potential adjuvant treatment strategies for early prevention and treatment of schistosomiasis japonica.}, }
@article {pmid38440794, year = {2024}, author = {Favero, G and Gianò, M and Franco, C and Pinto, D and van Noorden, CJF and Rinaldi, F and Rezzani, R}, title = {Relation Between Reactive Oxygen Species Production and Transient Receptor Potential Vanilloid1 Expression in Human Skin During Aging.}, journal = {The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society}, volume = {72}, number = {3}, pages = {157-171}, pmid = {38440794}, issn = {1551-5044}, mesh = {Adult ; Aged ; Humans ; Aging ; *Endothelial Cells/metabolism ; Epidermis ; Keratinocytes ; Reactive Oxygen Species/metabolism ; *Skin/metabolism ; }, abstract = {Skin sensitivity and impaired epidermal barrier function are associated with aging and are at least partly due to increased production of reactive oxygen species (ROS). Transient receptor potential vanilloid1 (TRPV1) is expressed in keratinocytes, fibroblasts, mast cells, and endothelial cells in skin. We investigated in skin biopsies of adult and elderly donors whether TRPV1 expression is involved in the skin aging process. We found that aging skin showed a strongly reduced epidermal thickness, strongly increased oxidative stress, protease expression, and mast cell degranulation and strongly increased TRPV1 expression both in epidermis and dermis. Based on our findings, the aging-related changes observed in the epidermis of the skin level are associated with increased ROS production, and hypothesized alterations in TRPV1 expression are mechanistically linked to this process.}, }
@article {pmid38436256, year = {2024}, author = {Ling, J and Hryckowian, AJ}, title = {Re-framing the importance of Group B Streptococcus as a gut-resident pathobiont.}, journal = {Infection and immunity}, volume = {92}, number = {9}, pages = {e0047823}, pmid = {38436256}, issn = {1098-5522}, support = {R35 GM150996/GM/NIGMS NIH HHS/United States ; R35GM150996//HHS | NIH | National Institute of General Medical Sciences (NIGMS)/ ; DGE-2137424//NSF | National Science Foundation Graduate Research Fellowship Program (GRFP)/ ; 1U48DP006383//UW-Madison Prevention Research Center/ ; Gift//Judy L. and Sal A. Troia/ ; }, mesh = {*Streptococcus agalactiae ; Humans ; *Streptococcal Infections/microbiology ; *Gastrointestinal Microbiome/physiology ; Gastrointestinal Tract/microbiology ; Animals ; }, abstract = {Streptococcus agalactiae (Group B Streptococcus, GBS) is a Gram-positive bacterial species that causes disease in humans across the lifespan. While antibiotics are used to mitigate GBS infections, it is evident that antibiotics disrupt human microbiomes (which can predispose people to other diseases later in life), and antibiotic resistance in GBS is on the rise. Taken together, these unintended negative impacts of antibiotics highlight the need for precision approaches for minimizing GBS disease. One possible approach involves selectively depleting GBS in its commensal niches before it can cause disease at other body sites or be transmitted to at-risk individuals. One understudied commensal niche of GBS is the adult gastrointestinal (GI) tract, which may predispose colonization at other body sites in individuals at risk for GBS disease. However, a better understanding of the host-, microbiome-, and GBS-determined variables that dictate GBS GI carriage is needed before precise GI decolonization approaches can be developed. In this review, we synthesize current knowledge of the diverse body sites occupied by GBS as a pathogen and as a commensal. We summarize key molecular factors GBS utilizes to colonize different host-associated niches to inform future efforts to study GBS in the GI tract. We also discuss other GI commensals that are pathogenic in other body sites to emphasize the broader utility of precise de-colonization approaches for mitigating infections by GBS and other bacterial pathogens. Finally, we highlight how GBS treatments could be improved with a more holistic understanding of GBS enabled by continued GI-focused study.}, }
@article {pmid38432422, year = {2024}, author = {Murali, SK and Mansell, TJ}, title = {Next generation probiotics: Engineering live biotherapeutics.}, journal = {Biotechnology advances}, volume = {72}, number = {}, pages = {108336}, doi = {10.1016/j.biotechadv.2024.108336}, pmid = {38432422}, issn = {1873-1899}, mesh = {Humans ; *Probiotics/therapeutic use ; Prebiotics ; *Microbiota ; }, abstract = {The population dynamics of the human microbiome have been associated with inflammatory bowel disease, cancer, obesity, autoimmune diseases, and many other human disease states. An emerging paradigm in treatment is the administration of live engineered organisms, also called next-generation probiotics. However, the efficacy of these microbial therapies can be limited by the organism's overall performance in the harsh and nutrient-limited environment of the gut. In this review, we summarize the current state of the art use of bacterial and yeast strains as probiotics, highlight the recent development of genetic tools for engineering new therapeutic functions in these organisms, and report on the latest therapeutic applications of engineered probiotics, including recent clinical trials. We also discuss the supplementation of prebiotics as a method of manipulating the microbiome and improving the overall performance of engineered live biotherapeutics.}, }
@article {pmid38430912, year = {2024}, author = {Fang, S and Luo, Z and Wei, Z and Qin, Y and Zheng, J and Zhang, H and Jin, J and Li, J and Miao, C and Yang, S and Li, Y and Liang, Z and Yu, XD and Zhang, XM and Xiong, W and Zhu, H and Gan, WB and Huang, L and Li, B}, title = {Sexually dimorphic control of affective state processing and empathic behaviors.}, journal = {Neuron}, volume = {112}, number = {9}, pages = {1498-1517.e8}, doi = {10.1016/j.neuron.2024.02.001}, pmid = {38430912}, issn = {1097-4199}, mesh = {Animals ; Male ; Female ; Mice ; *Sex Characteristics ; *Empathy/physiology ; Piriform Cortex/physiology/metabolism ; Cues ; Mice, Inbred C57BL ; Affect/physiology ; Neurons/physiology/metabolism ; Behavior, Animal/physiology ; }, abstract = {Recognizing the affective states of social counterparts and responding appropriately fosters successful social interactions. However, little is known about how the affective states are expressed and perceived and how they influence social decisions. Here, we show that male and female mice emit distinct olfactory cues after experiencing distress. These cues activate distinct neural circuits in the piriform cortex (PiC) and evoke sexually dimorphic empathic behaviors in observers. Specifically, the PiC → PrL pathway is activated in female observers, inducing a social preference for the distressed counterpart. Conversely, the PiC → MeA pathway is activated in male observers, evoking excessive self-grooming behaviors. These pathways originate from non-overlapping PiC neuron populations with distinct gene expression signatures regulated by transcription factors and sex hormones. Our study unveils how internal states of social counterparts are processed through sexually dimorphic mechanisms at the molecular, cellular, and circuit levels and offers insights into the neural mechanisms underpinning sex differences in higher brain functions.}, }
@article {pmid38429112, year = {2024}, author = {Pust, MM and Rocha Castellanos, DM and Rzasa, K and Dame, A and Pishchany, G and Assawasirisin, C and Liss, A and Fernandez-Del Castillo, C and Xavier, RJ}, title = {Absence of a pancreatic microbiome in intraductal papillary mucinous neoplasm.}, journal = {Gut}, volume = {73}, number = {7}, pages = {1131-1141}, pmid = {38429112}, issn = {1468-3288}, support = {P30 DK043351/DK/NIDDK NIH HHS/United States ; }, mesh = {Humans ; Male ; Female ; *Microbiota ; *Pancreatic Neoplasms/microbiology/pathology ; Aged ; Middle Aged ; *Pancreatic Intraductal Neoplasms/microbiology/pathology ; *RNA, Ribosomal, 16S ; Carcinoma, Pancreatic Ductal/microbiology/pathology ; Cyst Fluid/microbiology ; Adenocarcinoma, Mucinous/microbiology/pathology ; Aged, 80 and over ; Pancreas/microbiology ; Adult ; }, abstract = {OBJECTIVE: This study aims to validate the existence of a microbiome within intraductal papillary mucinous neoplasm (IPMN) that can be differentiated from the taxonomically diverse DNA background of next-generation sequencing procedures.<br><br>DESIGN: We generated 16S rRNA amplicon sequencing data to analyse 338 cyst fluid samples from 190 patients and 19 negative controls, the latter collected directly from sterile syringes in the operating room. A subset of samples (n=20) and blanks (n=5) were spiked with known concentrations of bacterial cells alien to the human microbiome to infer absolute abundances of microbial traces. All cyst fluid samples were obtained intraoperatively and included IPMNs with various degrees of dysplasia as well as other cystic neoplasms. Follow-up culturing experiments were conducted to assess bacterial growth for microbiologically significant signals.<br><br>RESULTS: Microbiome signatures of cyst fluid samples were inseparable from those of negative controls, with no difference in taxonomic diversity, and microbial community composition. In a patient subgroup that had recently undergone invasive procedures, a bacterial signal was evident. This outlier signal was not characterised by higher taxonomic diversity but by an increased dominance index of a gut-associated microbe, leading to lower taxonomic evenness compared with the background signal.<br><br>CONCLUSION: The 'microbiome' of IPMNs and other pancreatic cystic neoplasms does not deviate from the background signature of negative controls, supporting the concept of a sterile environment. Outlier signals may appear in a small fraction of patients following recent invasive endoscopic procedures. No associations between microbial patterns and clinical or cyst parameters were apparent.}, }
@article {pmid38426063, year = {2024}, author = {Argentini, C and Lugli, GA and Tarracchini, C and Fontana, F and Mancabelli, L and Viappiani, A and Anzalone, R and Angelini, L and Alessandri, G and Longhi, G and Bianchi, MG and Taurino, G and Bussolati, O and Milani, C and van Sinderen, D and Turroni, F and Ventura, M}, title = {Genomic and ecological approaches to identify the Bifidobacterium breve prototype of the healthy human gut microbiota.}, journal = {Frontiers in microbiology}, volume = {15}, number = {}, pages = {1349391}, pmid = {38426063}, issn = {1664-302X}, abstract = {Members of the genus Bifidobacterium are among the first microorganisms colonizing the human gut. Among these species, strains of Bifidobacterium breve are known to be commonly transmitted from mother to her newborn, while this species has also been linked with activities supporting human wellbeing. In the current study, an in silico approach, guided by ecology- and phylogenome-based analyses, was employed to identify a representative strain of B. breve to be exploited as a novel health-promoting candidate. The selected strain, i.e., B. breve PRL2012, was found to well represent the genetic content and functional genomic features of the B. breve taxon. We evaluated the ability of PRL2012 to survive in the gastrointestinal tract and to interact with other human gut commensal microbes. When co-cultivated with various human gut commensals, B. breve PRL2012 revealed an enhancement of its metabolic activity coupled with the activation of cellular defense mechanisms to apparently improve its survivability in a simulated ecosystem resembling the human microbiome.}, }
@article {pmid38424056, year = {2024}, author = {Istvan, P and Birkeland, E and Avershina, E and Kværner, AS and Bemanian, V and Pardini, B and Tarallo, S and de Vos, WM and Rognes, T and Berstad, P and Rounge, TB}, title = {Exploring the gut DNA virome in fecal immunochemical test stool samples reveals associations with lifestyle in a large population-based study.}, journal = {Nature communications}, volume = {15}, number = {1}, pages = {1791}, pmid = {38424056}, issn = {2041-1723}, support = {198048//Kreftforeningen (Norwegian Cancer Society)/ ; 190179//Kreftforeningen (Norwegian Cancer Society)/ ; 2022067//Ministry of Health and Care Services | Helse S&#xf8;r-&#xd8;st RHF (Southern and Eastern Norway Regional Health Authority)/ ; }, mesh = {Humans ; Virome ; DNA Viruses/genetics ; *Viruses/genetics ; DNA ; *Colorectal Neoplasms/diagnosis/genetics ; }, abstract = {Stool samples for fecal immunochemical tests (FIT) are collected in large numbers worldwide as part of colorectal cancer screening programs. Employing FIT samples from 1034 CRCbiome participants, recruited from a Norwegian colorectal cancer screening study, we identify, annotate and characterize more than 18000 DNA viruses, using shotgun metagenome sequencing. Only six percent of them are assigned to a known taxonomic family, with Microviridae being the most prevalent viral family. Linking individual profiles to comprehensive lifestyle and demographic data shows 17/25 of the variables to be associated with the gut virome. Physical activity, smoking, and dietary fiber consumption exhibit strong and consistent associations with both diversity and relative abundance of individual viruses, as well as with enrichment for auxiliary metabolic genes. We demonstrate the suitability of FIT samples for virome analysis, opening an opportunity for large-scale studies of this enigmatic part of the gut microbiome. The diverse viral populations and their connections to the individual lifestyle uncovered herein paves the way for further exploration of the role of the gut virome in health and disease.}, }
@article {pmid38422909, year = {2024}, author = {Cena, JA and Belmok, A and Kyaw, CM and Dame-Teixeira, N}, title = {The Archaea domain: Exploring historical and contemporary perspectives with in silico primer coverage analysis for future research in Dentistry.}, journal = {Archives of oral biology}, volume = {161}, number = {}, pages = {105936}, doi = {10.1016/j.archoralbio.2024.105936}, pmid = {38422909}, issn = {1879-1506}, mesh = {Humans ; *Archaea/genetics ; Bacteria ; *Microbiota ; Mouth ; Dentistry ; Phylogeny ; }, abstract = {OBJECTIVE: The complete picture of how the human microbiome interacts with its host is still largely unknown, particularly concerning microorganisms beyond bacteria. Although existing in very low abundance and not directly linked to causing diseases, archaea have been detected in various sites of the human body, including the gastrointestinal tract, oral cavity, skin, eyes, respiratory and urinary systems. But what exactly are these microorganisms? In the early 1990 s, archaea were classified as a distinct domain of life, sharing a more recent common ancestor with eukaryotes than with bacteria. While archaea's presence and potential significance in Dentistry remain under-recognized, there are concerns that they may contribute to oral dysbiosis. However, detecting archaea in oral samples presents challenges, including difficulties in culturing, the selection of DNA extraction methods, primer design, bioinformatic analysis, and databases.<br><br>DESIGN: This is a comprehensive review on the oral archaeome, presenting an in-depth in silico analysis of various primers commonly used for detecting archaea in human body sites.<br><br>RESULTS: Among several primer pairs used for detecting archaea in human samples across the literature, only one specifically designed for detecting methanogenic archaea in stool samples, exhibited exceptional coverage levels for the domain and various archaea phyla.<br><br>CONCLUSIONS: Our in silico analysis underscores the need for designing new primers targeting not only methanogenic archaea but also nanoarchaeal and thaumarchaeota groups to gain a comprehensive understanding of the archaeal oral community. By doing so, researchers can pave the way for further advancements in the field of oral archaeome research.}, }
@article {pmid38419554, year = {2024}, author = {Korpela, K and Hurley, S and Ford, SA and Franklin, R and Byrne, S and Lunjani, N and Forde, B and Neogi, U and Venter, C and Walter, J and Hourihane, J and O'Mahony, L and , }, title = {Association between gut microbiota development and allergy in infants born during pandemic-related social distancing restrictions.}, journal = {Allergy}, volume = {79}, number = {7}, pages = {1938-1951}, doi = {10.1111/all.16069}, pmid = {38419554}, issn = {1398-9995}, support = {/SFI_/Science Foundation Ireland/Ireland ; //Childrens Health Ireland/ ; }, mesh = {Humans ; *Gastrointestinal Microbiome ; *COVID-19/prevention &amp; control/epidemiology ; Infant ; Female ; *Hypersensitivity/epidemiology/etiology ; Male ; *SARS-CoV-2 ; Feces/microbiology ; Physical Distancing ; Pandemics ; Environmental Exposure/adverse effects ; Child, Preschool ; Cohort Studies ; }, abstract = {BACKGROUND: Several hypotheses link reduced microbial exposure to increased prevalence of allergies. Here we capitalize on the opportunity to study a cohort of infants (CORAL), raised during COVID-19 associated social distancing measures, to identify the environmental exposures and dietary factors that contribute to early life microbiota development and to examine their associations with allergic outcomes.<br><br>METHODS: Fecal samples were sequenced from infants at 6 (n&#x2009;=&#x2009;351) and repeated at 12 (n&#x2009;=&#x2009;343) months, using 16S sequencing. Published 16S data from pre-pandemic cohorts were included for microbiota comparisons. Online questionnaires collected epidemiological information on home environment, healthcare utilization, infant health, allergic diseases, and diet. Skin prick testing (SPT) was performed at 12 (n&#x2009;=&#x2009;343) and 24 (n&#x2009;=&#x2009;320) months of age, accompanied by atopic dermatitis and food allergy assessments.<br><br>RESULTS: The relative abundance of bifidobacteria was higher, while environmentally transmitted bacteria such as Clostridia was lower in CORAL infants compared to previous cohorts. The abundance of multiple Clostridia taxa correlated with a microbial exposure index. Plant based foods during weaning positively impacted microbiota development. Bifidobacteria levels at 6&#x2009;months of age, and relative abundance of butyrate producers at 12&#x2009;months of age, were negatively associated with AD and SPT positivity. The prevalence of allergen sensitization, food allergy, and AD did not increase over pre-pandemic levels.<br><br>CONCLUSIONS: Environmental exposures and dietary components significantly impact microbiota community assembly. Our results also suggest that vertically transmitted bacteria and appropriate dietary supports may be more important than exposure to environmental microbes alone for protection against allergic diseases in infancy.}, }
@article {pmid38416678, year = {2024}, author = {Schwartzman, JA and Lebreton, F and Salamzade, R and Shea, T and Martin, MJ and Schaufler, K and Urhan, A and Abeel, T and Camargo, ILBC and Sgardioli, BF and Prichula, J and Guedes Frazzon, AP and Giribet, G and Van Tyne, D and Treinish, G and Innis, CJ and Wagenaar, JA and Whipple, RM and Manson, AL and Earl, AM and Gilmore, MS}, title = {Global diversity of enterococci and description of 18 previously unknown species.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {121}, number = {10}, pages = {e2310852121}, pmid = {38416678}, issn = {1091-6490}, support = {F32 GM121005/GM/NIGMS NIH HHS/United States ; P01 AI083214/AI/NIAID NIH HHS/United States ; U19 AI110818/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Humans ; Enterococcus/genetics ; Anti-Bacterial Agents/pharmacology ; *Enterococcus faecium/genetics ; Enterococcus faecalis/genetics ; Phylogeny ; Microbial Sensitivity Tests ; *Gram-Positive Bacterial Infections ; Drug Resistance, Bacterial ; }, abstract = {Enterococci are gut microbes of most land animals. Likely appearing first in the guts of arthropods as they moved onto land, they diversified over hundreds of millions of years adapting to evolving hosts and host diets. Over 60 enterococcal species are now known. Two species, Enterococcus faecalis and Enterococcus faecium, are common constituents of the human microbiome. They are also now leading causes of multidrug-resistant hospital-associated infection. The basis for host association of enterococcal species is unknown. To begin identifying traits that drive host association, we collected 886 enterococcal strains from widely diverse hosts, ecologies, and geographies. This identified 18 previously undescribed species expanding genus diversity by >25%. These species harbor diverse genes including toxins and systems for detoxification and resource acquisition. Enterococcus faecalis and E. faecium were isolated from diverse hosts highlighting their generalist properties. Most other species showed a more restricted distribution indicative of specialized host association. The expanded species diversity permitted the Enterococcus genus phylogeny to be viewed with unprecedented resolution, allowing features to be identified that distinguish its four deeply rooted clades, and the entry of genes associated with range expansion such as B-vitamin biosynthesis and flagellar motility to be mapped to the phylogeny. This work provides an unprecedentedly broad and deep view of the genus Enterococcus, including insights into its evolution, potential new threats to human health, and where substantial additional enterococcal diversity is likely to be found.}, }
@article {pmid38409417, year = {2024}, author = {Raslan, MA and Raslan, SA and Shehata, EM and Mahmoud, AS and Viana, MVC and Aburjaile, F and Barh, D and Sabri, NA and Azevedo, V}, title = {Mass Spectrometry Applications to Study Human Microbiome.}, journal = {Advances in experimental medicine and biology}, volume = {1443}, number = {}, pages = {87-101}, pmid = {38409417}, issn = {0065-2598}, mesh = {Humans ; *Microbiota ; Mass Spectrometry/methods ; *Gastrointestinal Microbiome ; Metabolomics/methods ; High-Throughput Nucleotide Sequencing ; }, abstract = {Microbiotas are an adaptable component of ecosystems, including human ecology. Microorganisms influence the chemistry of their specialized niche, such as the human gut, as well as the chemistry of distant surroundings, such as other areas of the body. Metabolomics based on mass spectrometry (MS) is one of the primary methods for detecting and identifying small compounds generated by the human microbiota, as well as understanding the functional significance of these microbial metabolites. This book chapter gives basic knowledge on the kinds of untargeted mass spectrometry as well as the data types that may be generated in the context of microbiome study. While data analysis remains a barrier, the emphasis is on data analysis methodologies and integrative analysis, particularly the integration of microbiome sequencing data. Mass spectrometry (MS)-based techniques have resurrected culture methods for studying the human gut microbiota, filling in the gaps left by high-throughput sequencing methods in terms of culturing minor populations.}, }
@article {pmid38401105, year = {2024}, author = {Vijayanna, ST and Mane, S and Bhalerao, S and Jaideep, SS}, title = {Ayurvedic Therapies to Target the Microbiome: Evidence and Possibilities.}, journal = {Alternative therapies in health and medicine}, volume = {30}, number = {2}, pages = {76-83}, pmid = {38401105}, issn = {1078-6791}, mesh = {Humans ; Medicine, Ayurvedic ; *Microbiota ; *Gastrointestinal Microbiome ; India ; Life Style ; }, abstract = {CONTEXT: The microbiome is a constantly evolving entity, being influenced by diet, lifestyle, age, genetics, medication, and environment; keeping the microbiome in good health is a step toward better health for the body. Ayurveda emphasizes a healthy internal milieu that synchronizes with the circadian and seasonal rhythms, in addition to reacting to other stressors.<br><br>OBJECTIVE: The current review intended to provide an overview of Ayurvedic principles related to health and disease and their management and to briefly discuss the current understanding of the human microbiome and explore Ayurvedic herbs and therapies that have been studied for their effects on the microbiome.<br><br>DESIGN: The team included researchers in India and Canada. A Pubmed search was performed using the keywords Ayurveda therapies, Ayurvedic therapies, Gut microbiome, Panchakarma, Therapeutic purgation, Therapeutic emesis, medicated enema.<br><br>RESULTS: Research connecting Ayurvedic interventions and the gut microbiome is yet in a nascent stage. Several Ayurvedic herbs have been researched for their potential in altering the gut microbiome. Among the Ayurvedic therapies, virechana (therapeutic purgation) and basti (medicated enema) have been studied for their gut microbiome altering effects. However, the limited number of such studies prevents from drawing categorical conclusions currently, about the effects of Ayurvedic Panchakarma therapy on the human microbiome.<br><br>CONCLUSIONS: Studying where and how the Ayurvedic herbs and therapies can exert their influence on the human microbiome provides a challenging yet novel opportunity and can help address multiple health and disease conditions.}, }
@article {pmid38400752, year = {2024}, author = {He, Z and Xie, H and Xu, H and Wu, J and Zeng, W and He, Q and Jobin, C and Jin, S and Lan, P}, title = {Chemotherapy-induced microbiota exacerbates the toxicity of chemotherapy through the suppression of interleukin-10 from macrophages.}, journal = {Gut microbes}, volume = {16}, number = {1}, pages = {2319511}, pmid = {38400752}, issn = {1949-0984}, mesh = {Humans ; Mice ; Animals ; Oxaliplatin/toxicity ; Interleukin-10/genetics ; *Gastrointestinal Microbiome/genetics ; *Microbiota ; Macrophages ; *Probiotics/pharmacology/therapeutic use ; *Antineoplastic Agents/adverse effects ; }, abstract = {The gut microbiota has been shown to influence the efficacy and toxicity of chemotherapy, thereby affecting treatment outcomes. Understanding the mechanism by which microbiota affects chemotherapeutic toxicity would have a profound impact on cancer management. In this study, we report that fecal microbiota transplantation from oxaliplatin-exposed mice promotes toxicity in recipient mice. Splenic RNA sequencing and macrophage depletion experiment showed that the microbiota-induced toxicity of oxaliplatin in mice was dependent on macrophages. Furthermore, oxaliplatin-mediated toxicity was exacerbated in Il10[-/-] mice, but not attenuated in Rag1[-/-] mice. Adoptive transfer of macrophage into Il10[-/-] mice confirmed the role of macrophage-derived IL-10 in the improvement of oxaliplatin-induced toxicity. Depletion of fecal Lactobacillus and Bifidobacterium was associated with the exacerbation of oxaliplatin-mediated toxicity, whereas supplementation with these probiotics alleviated chemotherapy-induced toxicity. Importantly, IL-10 administration and probiotics supplementation did not attenuate the antitumor efficacy of chemotherapy. Clinically, patients with colorectal cancer exposed to oxaliplatin exhibited downregulation of peripheral CD45[+]IL-10[+] cells. Collectively, our findings indicate that microbiota-mediated IL-10 production influences tolerance to chemotherapy, and thus represents a potential clinical target.}, }
@article {pmid38398875, year = {2024}, author = {Simões, R and Ribeiro, AC and Dias, R and Freitas, V and Soares, S and Pérez-Gregorio, R}, title = {Unveiling the Immunomodulatory Potential of Phenolic Compounds in Food Allergies.}, journal = {Nutrients}, volume = {16}, number = {4}, pages = {}, pmid = {38398875}, issn = {2072-6643}, mesh = {Humans ; *Food Hypersensitivity ; Allergens ; Food ; Diet ; Phenols/pharmacology ; Mouth/pathology ; }, abstract = {Food allergies are becoming ever more prevalent around the world. This pathology is characterized by the breakdown of oral tolerance to ingested food allergens, resulting in allergic reactions in subsequent exposures. Due to the possible severity of the symptoms associated with this pathology, new approaches to prevent it and reduce associated symptoms are of utmost importance. In this framework, dietary phenolic compounds appear as a tool with a not fully explored potential. Some phenolic compounds have been pointed to with the ability to modulate food allergies and possibly reduce their symptoms. These compounds can modulate food allergies through many different mechanisms, such as altering the bioaccessibility and bioavailability of potentially immunogenic peptides, by modulating the human immune system and by modulating the composition of the human microbiome that resides in the oral cavity and the gastrointestinal tract. This review deepens the state-of-the-art of the modulation of these mechanisms by phenolic compounds. While this review shows clear evidence that dietary supplementation with foods rich in phenolic compounds might constitute a new approach to the management of food allergies, it also highlights the need for further research to delve into the mechanisms of action of these compounds and decipher systematic structure/activity relationships.}, }
@article {pmid38397866, year = {2024}, author = {Longo, S and Del Chierico, F and Scanu, M and Toto, F and Legramante, JM and Rizza, S and Putignani, L and Federici, M}, title = {An Investigation of Metabolic Risk Factors and Gut Microbiota in Unexplained Syncope.}, journal = {Biomedicines}, volume = {12}, number = {2}, pages = {}, pmid = {38397866}, issn = {2227-9059}, support = {2017FM74HK//Ministry of University and Research (MUR) Progetti di Ricerca di Interesse Nazionale (PRIN)/ ; 875534//SOPHIA Innovative Medicines Initiative 2 Joint Undertaking (JU) under grant agreement/ ; ARS01_00876//PON BIO-D/ ; PE00000019//MUR-PNRR M4C2I1.3 PE6 project/ ; DM1062//RTDa contract/ ; }, abstract = {BACKGROUND: The pathogenesis of many syncopal episodes remains unexplained. Intestinal dysbiosis could be involved in the pathophysiological mechanisms of syncope due to its connection with the central nervous system via the microbiota-gut-brain axis. This pilot study aimed to explore the specific cardiometabolic risk factors and gut microbiota in unexplained syncope (US), compared to other types of syncope, to assess their similarity or verify their different origins.<br><br>METHODS: We studied 86 participants with syncope, who were divided into four groups: an orthostatic syncope group (OH, n = 24), a neuromediated syncope group (NMS, n = 26), a cardiological syncope group (CS, n = 9), and an unexplained syncope group (US, n = 27). We evaluated the anthropometric, clinical, and metabolic characteristics of the four groups; the &#x3b1;- and &#x3b2;-diversity; and the differences in the abundance of the microbial taxa.<br><br>RESULTS: The US group had a lower incidence of systolic hypertension at the first visit and a lower frequency of patients with nocturnal hypertension than the CS group. Compared to the OH and NMS groups, the US group had a higher incidence of carotid plaques and greater carotid intima-media thickness, respectively. The microbiota differed significantly between the US and CS groups, but not between the US group and the OH or NMS group.<br><br>CONCLUSIONS: We observed significant differences in the gut microbiota between CS and US. Future studies are necessary to evaluate the involvement of the gut microbiota in the complex pathogenesis of syncope and whether its analysis could support the interpretation of the pathophysiological mechasnisms underlying some episodes classifiable as US.}, }
@article {pmid38396668, year = {2024}, author = {Efremova, I and Maslennikov, R and Poluektova, E and Medvedev, O and Kudryavtseva, A and Krasnov, G and Fedorova, M and Romanikhin, F and Bakhitov, V and Aliev, S and Sedova, N and Kuropatkina, T and Ivanova, A and Zharkova, M and Pervushova, E and Ivashkin, V}, title = {Gut Microbiota and Biomarkers of Endothelial Dysfunction in Cirrhosis.}, journal = {International journal of molecular sciences}, volume = {25}, number = {4}, pages = {}, pmid = {38396668}, issn = {1422-0067}, support = {National Research Grant Russia 2019//Biocodex (France)/ ; }, mesh = {Humans ; *Hepatic Encephalopathy ; Ascites ; *Gastrointestinal Microbiome/genetics ; *Hypoalbuminemia ; RNA, Ribosomal, 16S ; Claudin-3 ; Endothelin-1 ; Nitrites ; Liver Cirrhosis/complications ; Biomarkers ; Sodium ; Dysbiosis/complications ; Peptide Fragments ; Lipopolysaccharide Receptors ; }, abstract = {Our aim was to study the association of endothelial dysfunction biomarkers with cirrhosis manifestations, bacterial translocation, and gut microbiota taxa. The fecal microbiome was assessed using 16S rRNA gene sequencing. Plasma levels of nitrite, big endothelin-1, asymmetric dimethylarginine (ADMA), presepsin, and claudin were measured as biomarkers of endothelial dysfunction, bacterial translocation, and intestinal barrier dysfunction. An echocardiography with simultaneous determination of blood pressure and heart rate was performed to evaluate hemodynamic parameters. Presepsin, claudin 3, nitrite, and ADMA levels were higher in cirrhosis patients than in controls. Elevated nitrite levels were associated with high levels of presepsin and claudin 3, the development of hemodynamic circulation, hypoalbuminemia, grade 2-3 ascites, overt hepatic encephalopathy, high mean pulmonary artery pressure, increased abundance of Proteobacteria and Erysipelatoclostridium, and decreased abundance of Oscillospiraceae, Subdoligranulum, Rikenellaceae, Acidaminococcaceae, Christensenellaceae, and Anaerovoracaceae. Elevated ADMA levels were associated with higher Child-Pugh scores, lower serum sodium levels, hypoalbuminemia, grade 2-3 ascites, milder esophageal varices, overt hepatic encephalopathy, lower mean pulmonary artery pressure, and low abundance of Erysipelotrichia and Erysipelatoclostridiaceae. High big endothelin-1 levels were associated with high levels of presepsin and sodium, low levels of fibrinogen and cholesterol, hypocoagulation, increased Bilophila and Coprobacillus abundances, and decreased Alloprevotella abundance.}, }
@article {pmid38394022, year = {2024}, author = {Mayes, C and Morar, N}, title = {Environmental Injustices within Us: The Case of the Human Microbiome and the Need for More Creative Bioethics.}, journal = {The American journal of bioethics : AJOB}, volume = {24}, number = {3}, pages = {67-70}, doi = {10.1080/15265161.2024.2303135}, pmid = {38394022}, issn = {1536-0075}, mesh = {Humans ; *Bioethics ; Social Justice/ethics ; *Microbiota ; }, }
@article {pmid38392903, year = {2024}, author = {Babar, S and Liu, E and Kaur, S and Hussain, J and Danaher, PJ and Anstead, GM}, title = {Pseudopropionibacterium propionicum as a Cause of Empyema; A Diagnosis with Next-Generation Sequencing.}, journal = {Pathogens (Basel, Switzerland)}, volume = {13}, number = {2}, pages = {}, pmid = {38392903}, issn = {2076-0817}, support = {n/a//MicroGenDX/ ; }, abstract = {Pseudopropionibacterium propionicum (P.p.) is an anaerobic, Gram-positive, branching beaded rod that is a component of the human microbiome. An infection of the thoracic cavity with P.p. can mimic tuberculosis (TB), nocardiosis, and malignancy. We present a case of a 77-year-old male who presented with dyspnea and a productive cough who was initially misdiagnosed with TB based on positive acid-fast staining of a pleural biopsy specimen and an elevated adenosine deaminase level of the pleural fluid. He was then diagnosed with nocardiosis based on the Gram stain of his pleural fluid that showed a Gram-positive beaded and branching rod. The pleural fluid specimen was culture-negative, but the diagnosis of thoracic P.p. infection was determined with next-generation sequencing (NGS). The patient was initially treated with imipenem and minocycline, then ceftriaxone and minocycline, and later changed to minocycline only. This report shows the utility of NGS in making a microbiological diagnosis when other techniques either failed to provide a result (culture) or gave misleading information (histopathologic exam, pleural fluid adenosine deaminase determination, and organism morphology on Gram stain).}, }
@article {pmid38392650, year = {2024}, author = {Kamel, M and Aleya, S and Alsubih, M and Aleya, L}, title = {Microbiome Dynamics: A Paradigm Shift in Combatting Infectious Diseases.}, journal = {Journal of personalized medicine}, volume = {14}, number = {2}, pages = {}, pmid = {38392650}, issn = {2075-4426}, support = {RGP2/343/44//Deanship of Scientific Research at King Khalid University/ ; }, abstract = {Infectious diseases have long posed a significant threat to global health and require constant innovation in treatment approaches. However, recent groundbreaking research has shed light on a previously overlooked player in the pathogenesis of disease-the human microbiome. This review article addresses the intricate relationship between the microbiome and infectious diseases and unravels its role as a crucial mediator of host-pathogen interactions. We explore the remarkable potential of harnessing this dynamic ecosystem to develop innovative treatment strategies that could revolutionize the management of infectious diseases. By exploring the latest advances and emerging trends, this review aims to provide a new perspective on combating infectious diseases by targeting the microbiome.}, }
@article {pmid38391403, year = {2024}, author = {Nguyen, M and Ahn, P and Dawi, J and Gargaloyan, A and Kiriaki, A and Shou, T and Wu, K and Yazdan, K and Venketaraman, V}, title = {The Interplay between Mycobacterium tuberculosis and Human Microbiome.}, journal = {Clinics and practice}, volume = {14}, number = {1}, pages = {198-213}, pmid = {38391403}, issn = {2039-7275}, abstract = {Tuberculosis (TB), a respiratory disease caused by Mycobacterium tuberculosis (Mtb), is a significant cause of mortality worldwide. The lung, a breeding ground for Mtb, was once thought to be a sterile environment, but has now been found to host its own profile of microbes. These microbes are critical in the development of the host immune system and can produce metabolites that aid in host defense against various pathogens. Mtb infection as well as antibiotics can shift the microbial profile, causing dysbiosis and dampening the host immune response. Additionally, increasing cases of drug resistant TB have impacted the success rates of the traditional therapies of isoniazid, rifampin, pyrazinamide, and ethambutol. Recent years have produced tremendous research into the human microbiome and its role in contributing to or attenuating disease processes. Potential treatments aimed at altering the gut-lung bacterial axis may offer promising results against drug resistant TB and help mitigate the effects of TB.}, }
@article {pmid38390467, year = {2024}, author = {Acosta-Pagán, K and Bolaños-Rosero, B and Pérez, C and Ortíz, AP and Godoy-Vitorino, F}, title = {Ecological competition in the oral mycobiome of Hispanic adults living in Puerto Rico associates with periodontitis.}, journal = {Journal of oral microbiology}, volume = {16}, number = {1}, pages = {2316485}, pmid = {38390467}, issn = {2000-2297}, support = {P20 GM103475/GM/NIGMS NIH HHS/United States ; U54 GM133807/GM/NIGMS NIH HHS/United States ; }, abstract = {Background: Fungi are a major component of the human microbiome that only recently received attention. The imbalance of indigenous fungal communities and environmental fungi present in the oral cavity may have a role in oral dysbiosis, which could exacerbate oral inflammatory diseases. Methods: We performed a cross-sectional study and recruited 88 participants aged 21 to 49 from sexually transmitted infection clinics in Puerto Rico. A full-mouth periodontal examination following the NHANES protocol defined periodontal severity (CDC/AAP). ITS2 (fungal) genes were amplified and sequenced for mycobiota characterization of yeast and environmental fungi. Environmental outdoor spore levels were measured daily by the American Academy of Allergy Asthma and Immunology San Juan station and defined by quartiles as spore scores. Results: Our data indicate polymicrobial colonization of yeast and environmental fungi in the oral cavity. Dominant taxa associated with periodontal disease included Saccharomyces cerevisiae, Rigidoporus vinctus, and Aspergillus penicilloides, while Candida albicans were found to be ubiquitous. Fungal aerosols were found to impact the oral cavity biofilm, likely due to competition and neutralization by inhaled outdoor and indoor fungal spores. Conclusion: To our knowledge, this is the first report showcasing the ecological competition of measured outdoor environmental fungi with the human oral mycobiota.}, }
@article {pmid38390219, year = {2023}, author = {Mortazavi, SMJ and Said-Salman, I and Mortazavi, AR and El Khatib, S and Sihver, L}, title = {How the adaptation of the human microbiome to harsh space environment can determine the chances of success for a space mission to Mars and beyond.}, journal = {Frontiers in microbiology}, volume = {14}, number = {}, pages = {1237564}, pmid = {38390219}, issn = {1664-302X}, abstract = {The ability of human cells to adapt to space radiation is essential for the well-being of astronauts during long-distance space expeditions, such as voyages to Mars or other deep space destinations. However, the adaptation of the microbiomes should not be overlooked. Microorganisms inside an astronaut's body, or inside the space station or other spacecraft, will also be exposed to radiation, which may induce resistance to antibiotics, UV, heat, desiccation, and other life-threatening factors. Therefore, it is essential to consider the potential effects of radiation not only on humans but also on their microbiomes to develop effective risk reduction strategies for space missions. Studying the human microbiome in space missions can have several potential benefits, including but not limited to a better understanding of the major effects space travel has on human health, developing new technologies for monitoring health and developing new radiation therapies and treatments. While radioadaptive response in astronauts' cells can lead to resistance against high levels of space radiation, radioadaptive response in their microbiome can lead to resistance against UV, heat, desiccation, antibiotics, and radiation. As astronauts and their microbiomes compete to adapt to the space environment. The microorganisms may emerge as the winners, leading to life-threatening situations due to lethal infections. Therefore, understanding the magnitude of the adaptation of microorganisms before launching a space mission is crucial to be able to develop effective strategies to mitigate the risks associated with radiation exposure. Ensuring the safety and well-being of astronauts during long-duration space missions and minimizing the risks linked with radiation exposure can be achieved by adopting this approach.}, }
@article {pmid38388538, year = {2024}, author = {Cao, Z and Fan, D and Sun, Y and Huang, Z and Li, Y and Su, R and Zhang, F and Li, Q and Yang, H and Zhang, F and Miao, Y and Lan, P and Wu, X and Zuo, T}, title = {The gut ileal mucosal virome is disturbed in patients with Crohn's disease and exacerbates intestinal inflammation in mice.}, journal = {Nature communications}, volume = {15}, number = {1}, pages = {1638}, pmid = {38388538}, issn = {2041-1723}, support = {82172323//National Natural Science Foundation of China (National Science Foundation of China)/ ; 32100134//National Natural Science Foundation of China (National Science Foundation of China)/ ; 82060107//National Natural Science Foundation of China (National Science Foundation of China)/ ; }, mesh = {Humans ; Animals ; Mice ; *Crohn Disease/pathology ; Virome ; *Inflammatory Bowel Diseases/pathology ; Intestinal Mucosa/metabolism ; Ileum/pathology ; *Bacteriophages ; Bacteria ; Inflammation/pathology ; }, abstract = {Gut bacteriome dysbiosis is known to be implicated in the pathogenesis of inflammatory bowel disease (IBD). Crohn's disease (CD) is an IBD subtype with extensive mucosal inflammation, yet the mucosal virome, an empirical modulator of the bacteriome and mucosal immunity, remains largely unclear regarding its composition and role. Here, we exploited trans-cohort CD patients and healthy individuals to compositionally and functionally investigate the small bowel (terminal ileum) virome and bacteriome. The CD ileal virome was characterised by an under-representation of both lytic and temperate bacteriophages (especially those targeting bacterial pathogens), particularly in patients with flare-up. Meanwhile, the virome-bacteriome ecology in CD ileal mucosa was featured by a lack of Bifidobacterium- and Lachnospiraceae-led mutualistic interactions between bacteria and bacteriophages; surprisingly it was more pronounced in CD remission than flare-up, underlining the refractory and recurrent nature of mucosal inflammation in CD. Lastly, we substantiated that ileal virions from CD patients causally exacerbated intestinal inflammation in IBD mouse models, by reshaping a gut virome-bacteriome ecology preceding intestinal inflammation (microbial trigger) and augmenting microbial sensing/defence pathways in the intestine cells (host response). Altogether, our results highlight the significance of mucosal virome in CD pathogenesis and importance of mucosal virome restoration in CD therapeutics.}, }
@article {pmid38384263, year = {2024}, author = {Li, L and Li, M and Chen, Y and Yu, Z and Cheng, P and Yu, Z and Cheng, W and Zhang, W and Wang, Z and Gao, X and Sun, H and Wang, X}, title = {Function and therapeutic prospects of next-generation probiotic Akkermansia muciniphila in infectious diseases.}, journal = {Frontiers in microbiology}, volume = {15}, number = {}, pages = {1354447}, pmid = {38384263}, issn = {1664-302X}, abstract = {Akkermansia muciniphila is a gram-negative bacterium that colonizes the human gut, making up 3-5% of the human microbiome. A. muciniphila is a promising next-generation probiotic with clinical application prospects. Emerging studies have reported various beneficial effects of A. muciniphila including anti-cancer, delaying aging, reducing inflammation, improving immune function, regulating nervous system function, whereas knowledge on its roles and mechanism in infectious disease is currently unclear. In this review, we summarized the basic characteristics, genome and phenotype diversity, the influence of A. muciniphila and its derived components on infectious diseases, such as sepsis, virus infection, enteric infection, periodontitis and foodborne pathogen induced infections. We also provided updates on mechanisms how A. muciniphila protects intestinal barrier integrity and modulate host immune response. In summary, we believe that A. muciniphila is a promising therapeutic probiotic that may be applied for the treatment of a variety of infectious diseases.}, }
@article {pmid38383422, year = {2024}, author = {Gaire, TN and Scott, HM and Noyes, NR and Ericsson, AC and Tokach, MD and William, H and Menegat, MB and Vinasco, J and Nagaraja, TG and Volkova, VV}, title = {Temporal dynamics of the fecal microbiome in female pigs from early life through estrus, parturition, and weaning of the first litter of piglets.}, journal = {Animal microbiome}, volume = {6}, number = {1}, pages = {7}, pmid = {38383422}, issn = {2524-4671}, abstract = {BACKGROUND: Age-associated changes in the gastrointestinal microbiome of young pigs have been robustly described; however, the temporal dynamics of the fecal microbiome of the female pig from early life to first parity are not well understood. Our objective was to describe microbiome and antimicrobial resistance dynamics of the fecal microbiome of breeding sows from early life through estrus, parturition and weaning of the first litter of piglets (i.e., from 3 to 53 weeks of age).<br><br>RESULTS: Our analysis revealed that fecal bacterial populations in developing gilts undergo changes consistent with major maturation milestones. As the pigs progressed towards first estrus, the fecal bacteriome shifted from Rikenellaceae RC9 gut group- and UCG-002-dominated enterotypes to Treponema- and Clostridium sensu stricto 1-dominated enterotypes. After first estrus, the fecal bacteriome stabilized, with minimal changes in enterotype transition and associated microbial diversity from estrus to parturition and subsequent weaning of first litter piglets. Unlike bacterial communities, fecal fungal communities exhibited low diversity with high inter- and intra-pig variability and an increased relative abundance of certain taxa at parturition, including Candida spp. Counts of resistant fecal bacteria also fluctuated over time, and were highest in early life and subsequently abated as the pigs progressed to adulthood.<br><br>CONCLUSIONS: This study provides insights into how the fecal microbial community and antimicrobial resistance in female pigs change from three weeks of age throughout their first breeding lifetime. The fecal bacteriome enterotypes and diversity are found to be age-driven and established by the time of first estrus, with minimal changes observed during subsequent physiological stages, such as parturition and lactation, when compared to the earlier age-related shifts. The use of pigs as a model for humans is well-established, however, further studies are needed to understand how our results compare to the human microbiome dynamics. Our findings suggest that the fecal microbiome exhibited consistent changes across individual pigs and became more diverse with age, which is a beneficial characteristic for an animal model system.}, }
@article {pmid38376378, year = {2024}, author = {Kitamura, N and Kajihara, T and Volpiano, CG and Naung, M and Méric, G and Hirabayashi, A and Yano, H and Yamamoto, M and Yoshida, F and Kobayashi, T and Yamanashi, S and Kawamura, T and Matsunaga, N and Okochi, J and Sugai, M and Yahara, K}, title = {Exploring the effects of antimicrobial treatment on the gut and oral microbiomes and resistomes from elderly long-term care facility residents via shotgun DNA sequencing.}, journal = {Microbial genomics}, volume = {10}, number = {2}, pages = {}, pmid = {38376378}, issn = {2057-5858}, mesh = {Aged ; Humans ; Angiotensin Receptor Antagonists ; Cross-Sectional Studies ; Long-Term Care ; Angiotensin-Converting Enzyme Inhibitors ; DNA ; Sequence Analysis, DNA ; *Microbiota ; *Anti-Infective Agents ; }, abstract = {Monitoring antibiotic-resistant bacteria (ARB) and understanding the effects of antimicrobial drugs on the human microbiome and resistome are crucial for public health. However, no study has investigated the association between antimicrobial treatment and the microbiome-resistome relationship in long-term care facilities, where residents act as reservoirs of ARB but are not included in the national surveillance for ARB. We conducted shotgun metagenome sequencing of oral and stool samples from long-term care facility residents and explored the effects of antimicrobial treatment on the human microbiome and resistome using two types of comparisons: cross-sectional comparisons based on antimicrobial treatment history in the past 6 months and within-subject comparisons between stool samples before, during and 2-4 weeks after treatment using a single antimicrobial drug. Cross-sectional analysis revealed two characteristics in the group with a history of antimicrobial treatment: the archaeon Methanobrevibacter was the only taxon that significantly increased in abundance, and the total abundance of antimicrobial resistance genes (ARGs) was also significantly higher. Within-subject comparisons showed that taxonomic diversity did not decrease during treatment, suggesting that the effect of the prescription of a single antimicrobial drug in usual clinical treatment on the gut microbiota is likely to be smaller than previously thought, even among very elderly people. Additional analysis of the detection limit of ARGs revealed that they could not be detected when contig coverage was <2.0. This study is the first to report the effects of usual antimicrobial treatments on the microbiome and resistome of long-term care facility residents.}, }
@article {pmid38374338, year = {2024}, author = {Buiatte, V and Fonseca, A and Alonso Madureira, P and Nakashima Vaz, AC and Tizioto, PC and Centola Vidal, AM and Ganda, E and de Azevedo Ruiz, VL}, title = {A comparative study of the bacterial diversity and composition of nursery piglets' oral fluid, feces, and housing environment.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {4119}, pmid = {38374338}, issn = {2045-2322}, support = {2017/22184-7//Funda&#xe7;&#xe3;o de Amparo &#xe0; Pesquisa do Estado de S&#xe3;o Paulo/ ; 001//Coordena&#xe7;&#xe3;o de Aperfei&#xe7;oamento de Pessoal de N&#xed;vel Superior/ ; PEN04752//Hatch/ ; }, mesh = {Swine ; Animals ; Humans ; *Gastrointestinal Microbiome ; RNA, Ribosomal, 16S/genetics ; Housing ; Bacteria/genetics ; Feces/microbiology ; Firmicutes/genetics ; }, abstract = {The oral cavity is the portal of entry for many microorganisms that affect swine, and the swine oral fluid has been used as a specimen for the diagnosis of several infectious diseases. The oral microbiota has been shown to play important roles in humans, such as protection against non-indigenous bacteria. In swine, studies that have investigated the microbial composition of the oral cavity of pigs are scarce. This study aimed to characterize the oral fluid microbiota of weaned pigs from five commercial farms in Brazil and compare it to their respective fecal and environmental microbiotas. Bacterial compositions were determined by 16S rRNA gene sequencing and analyzed in R Studio. Oral fluid samples were significantly less diverse (alpha diversity) than pen floor and fecal samples (P < 0.01). Alpha diversity changed among farms in oral fluid and pen floor samples, but no differences were observed in fecal samples. Permutational ANOVA revealed that beta diversity was significantly different among sample types (P = 0.001) and farms (P = 0.001), with separation of sample types (feces, pen floor, and oral fluid) on the principal coordinates analysis. Most counts obtained from oral fluid samples were classified as Firmicutes (80.4%) and Proteobacteria (7.7%). The genera Streptococcus, members of the Pasteurellaceae family, and Veillonella were differentially abundant in oral fluid samples when compared to fecal samples, in which Streptococcus was identified as a core genus that was strongly correlated (SparCC) with other taxa. Firmicutes and Bacteroidota were the most relatively abundant phyla identified in fecal and pen floor samples, and Prevotella_9 was the most classified genus. No differentially abundant taxa were identified when comparing fecal samples and pen floor samples. We concluded that under the conditions of our study, the oral fluid microbiota of weaned piglets is different (beta diversity) and less diverse (alpha diversity) than the fecal and environmental microbiotas. Several differentially abundant taxa were identified in the oral fluid samples, and some have been described as important colonizers of the oral cavity in human microbiome studies. Further understanding of the relationship between the oral fluid microbiota and swine is necessary and would create opportunities for the development of innovative solutions that target the microbiota to improve swine health and production.}, }
@article {pmid38371926, year = {2024}, author = {Yang, MQ and Wang, ZJ and Zhai, CB and Chen, LQ}, title = {Research progress on the application of 16S rRNA gene sequencing and machine learning in forensic microbiome individual identification.}, journal = {Frontiers in microbiology}, volume = {15}, number = {}, pages = {1360457}, pmid = {38371926}, issn = {1664-302X}, abstract = {Forensic microbiome research is a field with a wide range of applications and a number of protocols have been developed for its use in this area of research. As individuals host radically different microbiota, the human microbiome is expected to become a new biomarker for forensic identification. To achieve an effective use of this procedure an understanding of factors which can alter the human microbiome and determinations of stable and changing elements will be critical in selecting appropriate targets for investigation. The 16S rRNA gene, which is notable for its conservation and specificity, represents a potentially ideal marker for forensic microbiome identification. Gene sequencing involving 16S rRNA is currently the method of choice for use in investigating microbiomes. While the sequencing involved with microbiome determinations can generate large multi-dimensional datasets that can be difficult to analyze and interpret, machine learning methods can be useful in surmounting this analytical challenge. In this review, we describe the research methods and related sequencing technologies currently available for application of 16S rRNA gene sequencing and machine learning in the field of forensic identification. In addition, we assess the potential value of 16S rRNA and machine learning in forensic microbiome science.}, }
@article {pmid38371919, year = {2024}, author = {Wang, Q and Fan, X and Wu, S and Su, X}, title = {PM-CNN: microbiome status recognition and disease detection model based on phylogeny and multi-path neural network.}, journal = {Bioinformatics advances}, volume = {4}, number = {1}, pages = {vbae013}, pmid = {38371919}, issn = {2635-0041}, abstract = {MOTIVATION: The human microbiome, found throughout various body parts, plays a crucial role in health dynamics and disease development. Recent research has highlighted microbiome disparities between patients with different diseases and healthy individuals, suggesting the microbiome's potential in recognizing health states. Traditionally, microbiome-based status classification relies on pre-trained machine learning (ML) models. However, most ML methods overlook microbial relationships, limiting model performance.<br><br>RESULTS: To address this gap, we propose PM-CNN (Phylogenetic Multi-path Convolutional Neural Network), a novel phylogeny-based neural network model for multi-status classification and disease detection using microbiome data. PM-CNN organizes microbes based on their phylogenetic relationships and extracts features using a multi-path convolutional neural network. An ensemble learning method then fuses these features to make accurate classification decisions. We applied PM-CNN to human microbiome data for status and disease detection, demonstrating its significant superiority over existing ML models. These results provide a robust foundation for microbiome-based state recognition and disease prediction in future research and applications.<br><br>PM-CNN software is available at https://github.com/qdu-bioinfo/PM_CNN.}, }
@article {pmid38369542, year = {2024}, author = {Zou, S and Yang, C and Zhang, J and Zhong, D and Meng, M and Zhang, L and Chen, H and Fang, L}, title = {Multi-omic profiling reveals associations between the gut microbiome, host genome and transcriptome in patients with colorectal cancer.}, journal = {Journal of translational medicine}, volume = {22}, number = {1}, pages = {175}, pmid = {38369542}, issn = {1479-5876}, support = {82373512//National Natural Science Foundation of China/ ; 82222056//National Natural Science Foundation of China/ ; 82302910//National Natural Science Foundation of China/ ; 2022A1515012316//Natural Science Foundation of Guangdong Province/ ; 2021B1212010004//Natural Science Foundation of Guangdong Province/ ; }, mesh = {Humans ; *Gastrointestinal Microbiome/genetics ; Transcriptome/genetics ; *Colorectal Neoplasms/diagnosis ; Multiomics ; *Microbiota ; }, abstract = {BACKGROUND: Colorectal cancer (CRC) is the leading cancer worldwide. Microbial agents have been considered to contribute to the pathogenesis of different disease. But the underlying relevance between CRC and microbiota remain unclear.<br><br>METHODS: We dissected the fecal microbiome structure and genomic and transcriptomic profiles of matched tumor and normal mucosa tissues from 41 CRC patients. Of which, the relationship between CRC-associated bacterial taxa and their significantly correlated somatic mutated gene was investigated by exome sequencing technology. Differentially expressed functional genes in CRC were clustered according to their correlation with differentially abundant species, following by annotation with DAVID. The composition of immune and stromal cell types was identified by XCELL.<br><br>RESULTS: We identified a set of 22 microbial gut species associated with CRC and estimate the relative abundance of KEGG ontology categories. Next, the interactions between CRC-related gut microbes and clinical phenotypes were evaluated. 4 significantly mutated gene: TP53, APC, KRAS, SMAD4 were pointed out and the associations with cancer related microbes were identified. Among them, Fusobacterium nucleatum positively corelated with different host metabolic pathways. Finally, we revealed that Fusobacterium nucleatum modified the tumor immune environment by TNFSF9 gene expression.<br><br>CONCLUSION: Collectively, our multi-omics data could help identify novel biomarkers to inform clinical decision-making in the detection and diagnosis of CRC.}, }
@article {pmid38361239, year = {2024}, author = {Mohamed, ME and Saqr, A and Staley, C and Onyeaghala, G and Teigen, L and Dorr, CR and Remmel, RP and Guan, W and Oetting, WS and Matas, AJ and Israni, AK and Jacobson, PA}, title = {Pharmacomicrobiomics: Immunosuppressive Drugs and Microbiome Interactions in Transplantation.}, journal = {Transplantation}, volume = {108}, number = {9}, pages = {1895-1910}, pmid = {38361239}, issn = {1534-6080}, support = {R01 AI140303/AI/NIAID NIH HHS/United States ; }, mesh = {Humans ; *Immunosuppressive Agents/pharmacokinetics/adverse effects ; *Gastrointestinal Microbiome/drug effects ; *Organ Transplantation/adverse effects ; Graft Rejection/prevention &amp; control/immunology/microbiology ; Animals ; }, abstract = {The human microbiome is associated with human health and disease. Exogenous compounds, including pharmaceutical products, are also known to be affected by the microbiome, and this discovery has led to the field of pharmacomicobiomics. The microbiome can also alter drug pharmacokinetics and pharmacodynamics, possibly resulting in side effects, toxicities, and unanticipated disease response. Microbiome-mediated effects are referred to as drug-microbiome interactions (DMI). Rapid advances in the field of pharmacomicrobiomics have been driven by the availability of efficient bacterial genome sequencing methods and new computational and bioinformatics tools. The success of fecal microbiota transplantation for recurrent Clostridioides difficile has fueled enthusiasm and research in the field. This review focuses on the pharmacomicrobiome in transplantation. Alterations in the microbiome in transplant recipients are well documented, largely because of prophylactic antibiotic use, and the potential for DMI is high. There is evidence that the gut microbiome may alter the pharmacokinetic disposition of tacrolimus and result in microbiome-specific tacrolimus metabolites. The gut microbiome also impacts the enterohepatic recirculation of mycophenolate, resulting in substantial changes in pharmacokinetic disposition and systemic exposure. The mechanisms of these DMI and the specific bacteria or communities of bacteria are under investigation. There are little or no human DMI data for cyclosporine A, corticosteroids, and sirolimus. The available evidence in transplantation is limited and driven by small studies of heterogeneous designs. Larger clinical studies are needed, but the potential for future clinical application of the pharmacomicrobiome in avoiding poor outcomes is high.}, }
@article {pmid38352704, year = {2024}, author = {Kadyan, S and Park, G and Hochuli, N and Miller, K and Wang, B and Nagpal, R}, title = {Resistant starches from dietary pulses improve neurocognitive health via gut-microbiome-brain axis in aged mice.}, journal = {Frontiers in nutrition}, volume = {11}, number = {}, pages = {1322201}, pmid = {38352704}, issn = {2296-861X}, abstract = {INTRODUCTION: Cognitive decline is a common consequence of aging. Dietary patterns that lack fibers and are high in saturated fats worsen cognitive impairment by triggering pro-inflammatory pathways and metabolic dysfunctions. Emerging evidence highlights the neurocognitive benefits of fiber-rich diets and the crucial role of gut-microbiome-brain signaling. However, the mechanisms of this diet-microbiome-brain regulation remain largely unclear.<br><br>METHODS: Accordingly, we herein investigated the unexplored neuroprotective mechanisms of dietary pulses-derived resistant starch (RS) in improving aging-associated neurocognitive function in an aged (60-weeks old) murine model carrying a human microbiome.<br><br>RESULTS AND DISCUSSION: Following 20-weeks dietary regimen which included a western-style diet without (control; CTL) or with 5% w/w fortification with RS from pinto beans (PTB), black-eyed-peas (BEP), lentils (LEN), chickpeas (CKP), or inulin fiber (INU), we find that RS, particularly from LEN, ameliorate the cognitive impairments induced by western diet. Mechanistically, RS-mediated improvements in neurocognitive assessments are attributed to positive remodeling of the gut microbiome-metabolome arrays, which include increased short-chain fatty acids and reduced branched-chain amino acids levels. This microbiome-metabolite-brain signaling cascade represses neuroinflammation, cellular senescence, and serum leptin/insulin levels, while enhancing lipid metabolism through improved hepatic function. Altogether, the data demonstrate the prebiotic effects of RS in improving neurocognitive function via modulating the gut-brain axis.}, }
@article {pmid38352363, year = {2024}, author = {Zhou, X and Shen, X and Johnson, JS and Spakowicz, DJ and Agnello, M and Zhou, W and Avina, M and Honkala, A and Chleilat, F and Chen, SJ and Cha, K and Leopold, S and Zhu, C and Chen, L and Lyu, L and Hornburg, D and Wu, S and Zhang, X and Jiang, C and Jiang, L and Jiang, L and Jian, R and Brooks, AW and Wang, M and Contrepois, K and Gao, P and Schüssler-Fiorenza Rose, SM and Binh Tran, TD and Nguyen, H and Celli, A and Hong, BY and Bautista, EJ and Dorsett, Y and Kavathas, P and Zhou, Y and Sodergren, E and Weinstock, GM and Snyder, MP}, title = {Longitudinal profiling of the microbiome at four body sites reveals core stability and individualized dynamics during health and disease.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2024.02.01.577565}, pmid = {38352363}, issn = {2692-8205}, abstract = {UNLABELLED: To understand dynamic interplay between the human microbiome and host during health and disease, we analyzed the microbial composition, temporal dynamics, and associations with host multi-omics, immune and clinical markers of microbiomes from four body sites in 86 participants over six years. We found that microbiome stability and individuality are body-site-specific and heavily influenced by the host. The stool and oral microbiome were more stable than the skin and nasal microbiomes, possibly due to their interaction with the host and environment. Also, we identified individual-specific and commonly shared bacterial taxa, with individualized taxa showing greater stability. Interestingly, microbiome dynamics correlated across body sites, suggesting systemic coordination influenced by host-microbial-environment interactions. Notably, insulin-resistant individuals showed altered microbial stability and associations between microbiome, molecular markers, and clinical features, suggesting their disrupted interaction in metabolic disease. Our study offers comprehensive views of multi-site microbial dynamics and their relationship with host health and disease.<br><br>STUDY HIGHLIGHTS: The stability of the human microbiome varies among individuals and body sites.Highly individualized microbial genera are more stable over time.At each of the four body sites, systematic interactions between the environment, the host and bacteria can be detected.Individuals with insulin resistance have lower microbiome stability, a more diversified skin microbiome, and significantly altered host-microbiome interactions.}, }
@article {pmid38347963, year = {2023}, author = {Jokiranta, ST and Miettinen, S and Salonen, S and Kareinen, L and Uusitalo, R and Korhonen, EM and Virtanen, J and Kivistö, I and Aaltonen, K and Mosselhy, DA and Lääveri, T and Kantele, A and Arstila, TP and Jarva, H and Vapalahti, O and Heinonen, S and Kekäläinen, E}, title = {Stable Levels of Antibodies Against Unrelated Toxoid Vaccines After COVID-19: COVID-19 Infection Does Not Affect Toxoid Vaccine Antibody Levels.}, journal = {Pathogens &amp; immunity}, volume = {8}, number = {2}, pages = {74-87}, pmid = {38347963}, issn = {2469-2964}, abstract = {BACKGROUND: Lymphopenia is common in COVID-19. This has raised concerns that COVID-19 could affect the immune system akin to measles infection, which causes immune amnesia and a reduction in protective antibodies.<br><br>METHODS: We recruited COVID-19 patients (n = 59) in Helsinki, Finland, and collected plasma samples on 2 to 3 occasions during and after infection. We measured IgG antibodies to diphtheria toxin, tetanus toxoid, and pertussis toxin, along with total IgG, SARS-CoV-2 spike protein IgG, and neutralizing antibodies. We also surveyed the participants for up to 17 months for long-term impaired olfaction as a proxy for prolonged post-acute COVID-19 symptoms.<br><br>RESULTS: No significant differences were found in the unrelated vaccine responses while the serological response against COVID-19 was appropriate. During the acute phase of the disease, the SARSCoV-2 IgG levels were lower in outpatients when compared to inpatients. SARS-CoV-2 serology kinetics matched expectations. In the acute phase, anti-tetanus and anti-diphtheria IgG levels were lower in patients with prolonged impaired olfaction during follow up than in those without.<br><br>CONCLUSIONS: We could not detect significant decline in overall humoral immunity during or after COVID-19 infection. In severe COVID-19, there appears to be a temporary decline in total IgG levels.}, }
@article {pmid38346516, year = {2024}, author = {Hou, C and Huang, M and Wang, P and Zhang, Q and Wang, G and Gao, S}, title = {Chronic exposure to 3,6-dichlorocarbazole exacerbates non-alcoholic fatty liver disease in zebrafish by disrupting lipid metabolism and inducing special lipid biomarker accumulation.}, journal = {Chemosphere}, volume = {352}, number = {}, pages = {141442}, doi = {10.1016/j.chemosphere.2024.141442}, pmid = {38346516}, issn = {1879-1298}, mesh = {Animals ; *Non-alcoholic Fatty Liver Disease/chemically induced ; Zebrafish/metabolism ; Lipid Metabolism ; Liver/metabolism ; Triglycerides/metabolism ; *Perciformes/metabolism ; Biomarkers/metabolism ; Diet, High-Fat ; *Carbazoles ; }, abstract = {Most previous studies have focused primarily on the adverse effects of environmental chemicals on organisms of good healthy. Although global prevalence of non-alcoholic fatty liver disease (NAFLD) has reached approximately 25%, the impact of environmentally persistent organic chemicals on organisms with NAFLD is substantially unknown. Polyhalogenated carbazoles (PHCZs) as emerging contaminants have been frequently detected in the environment and organisms. In this study, we investigated the impact of the most frequently detected PHCZs, 3,6-dichlorocarbazole (36-CCZ), on zebrafish with high-fat diet (HFD)-induced NAFLD. After 4 weeks exposure to environmentally relevant concentrations of 36-CCZ (0.16-0.45 μg/L), the accumulation of lipid in zebrafish liver dramatically increased, and the transcription of genes involved in lipid synthesis, transport and oxidation was significantly upregulated, demonstrating that 36-CCZ had exacerbated the NAFLD in zebrafish. Lipidomic analysis indicated that 36-CCZ had significantly affected liver lipid metabolic pathways, mainly including glycerolipids and glycerophospholipids. Additionally, fifteen lipids were identified as potential lipid biomarkers for 36-CCZ exacerbation of NAFLD, including diacylglycerols (DGs), triglycerides (TGs), phosphatidylcholines (PCs), phosphatidylethanolamines (PEs), phosphatidic acid (PA), and phosphatidylinositol (PI). These findings demonstrate that long-term exposure to 36-CCZ can promote the progression of NAFLD, which will contribute to raising awareness of the health risks of PHCZs.}, }
@article {pmid38339836, year = {2024}, author = {Stevens, R and Gorman, S and Arabiat, D and Christophersen, CT and Palmer, DJ}, title = {Associations between sun exposure, skin pH, and epidermal permeability in pregnancy: A longitudinal observational study.}, journal = {Photochemistry and photobiology}, volume = {100}, number = {5}, pages = {1519-1526}, doi = {10.1111/php.13920}, pmid = {38339836}, issn = {1751-1097}, mesh = {Humans ; Female ; Pregnancy ; Hydrogen-Ion Concentration ; Longitudinal Studies ; *Sunlight ; Adult ; *Permeability ; *Skin/metabolism/radiation effects ; *Epidermis/radiation effects/metabolism ; Seasons ; }, abstract = {Little is known about how sun exposure may affect the maternal skin barrier during pregnancy when many hormonal and physiological changes occur. In this longitudinal observational study, 50 pregnant women were recruited at 18-24 weeks' gestation, 25 in summer-autumn, and 25 in winter-spring. At three time points in pregnancy at 18-24, 28-30, and 36-38 weeks' gestation, participants completed a validated sun exposure questionnaire and had skin permeability and surface pH measured on the volar forearm. We identified an association between increased sun exposure and increased skin permeability at 18-24 weeks' gestation (β = 0.85, p = 0.01). Lower transepidermal water loss (decreased skin permeability), mean = 12.1 (SD = 5.1) at 28-30 weeks' gestation was observed, compared to mean = 12.6 (SD = 4.0) at 18-24 weeks' and mean = 13.7 (SD = 8.5) at 36-38 weeks' gestation (n = 27, β = -1.83, p = 0.007). Higher skin pH readings, mean = 5.80 (SD = 0.58) were found at 28-30 weeks' gestation, compared to mean = 5.25 (SD = 0.62) at 18-24 weeks' and mean = 5.47 (SD = 0.57) at 36-38 weeks' gestation (n = 27, β = 0.40, p = 0.004). These gestational fluctuations remained after adjusting for Fitzpatrick skin type, season, and sun exposure. We observed gestational fluctuations in both skin permeability and skin pH, with 28-30 weeks' gestation being a significant point of difference compared to mid- and late-pregnancy periods.}, }
@article {pmid38337613, year = {2024}, author = {Efremova, I and Maslennikov, R and Zharkova, M and Poluektova, E and Benuni, N and Kotusov, A and Demina, T and Ivleva, A and Adzhieva, F and Krylova, T and Ivashkin, V}, title = {Efficacy and Safety of a Probiotic Containing Saccharomyces boulardii CNCM I-745 in the Treatment of Small Intestinal Bacterial Overgrowth in Decompensated Cirrhosis: Randomized, Placebo-Controlled Study.}, journal = {Journal of clinical medicine}, volume = {13}, number = {3}, pages = {}, pmid = {38337613}, issn = {2077-0383}, abstract = {(1) Background: The aim was to evaluate the effectiveness of the probiotic containing Saccharomyces boulardii in the treatment of small intestinal bacterial overgrowth (SIBO) in patients with decompensated cirrhosis. (2) Methods: This was a blinded, randomized, placebo-controlled study. (3) Results: After 3 months of treatment, SIBO was absent in 80.0% of patients in the probiotic group and in 23.1% of patients in the placebo group (p = 0.002). The patients with eliminated SIBO had decreased frequency of ascites and hepatic encephalopathy, the increased platelets and albumin levels, the decreased blood levels of total bilirubin, biomarkers of bacterial translocation (lipopolysaccharide [LPS]) and systemic inflammation (C-reactive protein), and positive changes in markers of hyperdynamic circulation compared with the state at inclusion. There were no significant changes in the claudin 3 level (the intestinal barrier biomarker) in these patients. No significant changes were observed in the group of patients with persistent SIBO. The serum level of nitrate (endothelial dysfunction biomarker) was lower in patients with eradicated SIBO than in patients with persistent SIBO. One (5.3%) patient with eradicated SIBO and six (42.9%) patients with persistent SIBO died within the first year of follow-up (p = 0.007). (4) Conclusions: SIBO eradication was an independent predictor of a favorable prognosis during the first year of follow-up.}, }
@article {pmid38333568, year = {2024}, author = {Bai, R and Guo, J}, title = {Interactions and Implications of Klebsiella pneumoniae with Human Immune Responses and Metabolic Pathways: A Comprehensive Review.}, journal = {Infection and drug resistance}, volume = {17}, number = {}, pages = {449-462}, pmid = {38333568}, issn = {1178-6973}, abstract = {Klebsiella pneumoniae (K. pneumoniae), a significant contributor to the global challenge of antibiotic resistance, is not only a ubiquitous component of the human microbiome but also a potent pathogen capable of causing a spectrum of diseases. This review provides a thorough analysis of the intricate interactions between K. pneumoniae and the human immune system, elucidating its substantial impact on metabolic processes. We explore the mechanisms employed by K. pneumoniae to evade and manipulate immune responses, including molecular mimicry, immune modulation, and biofilm formation. The review further investigates the bacterium's influence on metabolic pathways, particularly glycolysis, highlighting how these interactions exacerbate disease severity. The emergence of multidrug-resistant and extremely drug-resistant strains within the Enterobacteriaceae family has heightened the public health crisis, underscoring the urgency for comprehensive research. We investigate the roles of the host's complement system, autophagy, cell death mechanisms, and various cytokines in combating K. pneumoniae infections, shedding light on areas that warrant further academic investigation. Additionally, the review discusses the challenges posed by K1- and K2-capsule polysaccharides in vaccine development due to their complex molecular structures and adhesive properties. Acknowledging the limited availability of effective antimicrobials, this review advocates for exploring alternative approaches such as immunotherapeutics, vaccinations, and phage therapy. We consolidate current knowledge on K. pneumoniae, covering classical and non-classical subtypes, antimicrobial resistance-mediated genes, virulence factors, and epidemiological trends in isolation and antibiotic resistance rates. This comprehensive review not only advances our understanding of K. pneumoniae but also underscores the imperative for ongoing research and collaborative efforts to develop new prevention and treatment strategies against this formidable pathogen.}, }
@article {pmid38328082, year = {2024}, author = {Gray, SM and Moss, AD and Herzog, JW and Kashiwagi, S and Liu, B and Young, JB and Sun, S and Bhatt, A and Fodor, AA and Balfour Sartor, R}, title = {Mouse Adaptation of Human Inflammatory Bowel Diseases Microbiota Enhances Colonization Efficiency and Alters Microbiome Aggressiveness Depending on Recipient Colonic Inflammatory Environment.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {38328082}, issn = {2692-8205}, support = {P01 DK094779/DK/NIDDK NIH HHS/United States ; P40 OD010995/OD/NIH HHS/United States ; P30 DK034987/DK/NIDDK NIH HHS/United States ; P30 DK056350/DK/NIDDK NIH HHS/United States ; T32 DK007737/DK/NIDDK NIH HHS/United States ; }, abstract = {Understanding the cause vs consequence relationship of gut inflammation and microbial dysbiosis in inflammatory bowel diseases (IBD) requires a reproducible mouse model of human-microbiota-driven experimental colitis. Our study demonstrated that human fecal microbiota transplant (FMT) transfer efficiency is an underappreciated source of experimental variability in human microbiota associated (HMA) mice. Pooled human IBD patient fecal microbiota engrafted germ-free (GF) mice with low amplicon sequence variant (ASV)-level transfer efficiency, resulting in high recipient-to-recipient variation of microbiota composition and colitis severity in HMA Il-10[-/-] mice. In contrast, mouse-to-mouse transfer of mouse-adapted human IBD patient microbiota transferred with high efficiency and low compositional variability resulting in highly consistent and reproducible colitis phenotypes in recipient Il-10[-/-] mice. Human-to-mouse FMT caused a population bottleneck with reassembly of microbiota composition that was host inflammatory environment specific. Mouse-adaptation in the inflamed Il-10[-/-] host reassembled a more aggressive microbiota that induced more severe colitis in serial transplant to Il-10[-/-] mice than the distinct microbiota reassembled in non-inflamed WT hosts. Our findings support a model of IBD pathogenesis in which host inflammation promotes aggressive resident bacteria, which further drives a feed-forward process of dysbiosis exacerbated gut inflammation. This model implies that effective management of IBD requires treating both the dysregulated host immune response and aggressive inflammation-driven microbiota. We propose that our mouse-adapted human microbiota model is an optimized, reproducible, and rigorous system to study human microbiome-driven disease phenotypes, which may be generalized to mouse models of other human microbiota-modulated diseases, including metabolic syndrome/obesity, diabetes, autoimmune diseases, and cancer.}, }
@article {pmid38318164, year = {2024}, author = {Piazzesi, A and Pane, S and Del Chierico, F and Romani, L and Campana, A and Palma, P and Putignani, L}, title = {The pediatric gut bacteriome and virome in response to SARS-CoV-2 infection.}, journal = {Frontiers in cellular and infection microbiology}, volume = {14}, number = {}, pages = {1335450}, pmid = {38318164}, issn = {2235-2988}, mesh = {Adult ; Humans ; Child ; *COVID-19 ; Virome ; SARS-CoV-2/genetics ; *Microbiota ; Anti-Bacterial Agents/pharmacology/therapeutic use ; }, abstract = {INTRODUCTION: Since the beginning of the SARS-CoV-2 pandemic in early 2020, it has been apparent that children were partially protected from both infection and the more severe forms of the disease. Many different mechanisms have been proposed to explain this phenomenon, including children's frequent exposure to other upper respiratory infections and vaccines, and which inflammatory cytokines they are more likely to produce in response to infection. Furthermore, given the presence of SARS-CoV-2 in the intestine and its ability to infect enterocytes, combined with the well described immunomodulatory capabilities of the microbiome, another potential contributing factor may be the presence of certain protective microbial members of the gut microbiota (GM).<br><br>METHODS: We performed shotgun metagenomic sequencing and profiled both the bacteriome and virome of the GM of pediatric SARS-CoV-2 patients compared to healthy, age-matched subjects.<br><br>RESULTS: We found that, while pediatric patients do share some pro-inflammatory microbial signatures with adult patients, they also possess a distinct microbial signature of protective bacteria previously found to be negatively correlated with SARS-CoV-2 infectivity and COVID-19 severity. COVID-19 was also associated with higher fecal Cytomegalovirus load, and with shifts in the relative abundances of bacteriophages in the GM. Furthermore, we address how the preventative treatment of COVID-19 patients with antibiotics, a common practice especially in the early days of the pandemic, affected the bacteriome and virome, as well as the abundances of antimicrobial resistance and virulence genes in these patients.<br><br>DISCUSSION: To our knowledge, this is the first study to address the bacteriome, virome, and resistome of pediatric patients in response to COVID-19 and to preventative antibiotics use.}, }
@article {pmid38308184, year = {2024}, author = {Li, K and Zhang, J and Lyu, H and Yang, J and Wei, W and Wang, Y and Luo, H and Zhang, Y and Jiang, X and Yi, H and Wang, M and Zhang, C and Wu, K and Xiao, L and Wen, W and Xu, H and Li, G and Wan, Y and Yang, F and Yang, R and Fu, X and Qin, B and Zhou, Z and Zhang, H and Lee, MH}, title = {CSN6-SPOP-HMGCS1 Axis Promotes Hepatocellular Carcinoma Progression via YAP1 Activation.}, journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)}, volume = {11}, number = {14}, pages = {e2306827}, pmid = {38308184}, issn = {2198-3844}, support = {2020YFA0803300//National Key Research and Development Program/ ; 2018YFC0910300//National Key Research and Development Program/ ; 82203243//National Natural Science Foundation of China/ ; 82204411//National Natural Science Foundation of China/ ; 81971999//National Natural Science Foundation of China/ ; 2023A1515030245//Natural Science Foundation of Guangdong Province/ ; 2020A1515110076//Natural Science Foundation of Guangdong Province/ ; //"President Specific Funding" of The Sixth Affiliated Hospital, Sun Yat-sen University/ ; 2020B1111170004//Guangdong Provincial Clinical Research Center for Digestive Diseases/ ; //National Key Clinical Discipline/ ; }, mesh = {Humans ; *Carcinoma, Hepatocellular/metabolism ; Cholesterol/metabolism ; *Hydroxymethylglutaryl-CoA Synthase/metabolism ; *Liver Neoplasms/metabolism ; Nuclear Proteins/metabolism ; *Repressor Proteins/metabolism ; Tumor Microenvironment ; Ubiquitin/metabolism ; *YAP-Signaling Proteins/metabolism ; }, abstract = {Cholesterol metabolism has important roles in maintaining membrane integrity and countering the development of diseases such as obesity and cancers. Cancer cells sustain cholesterol biogenesis for their proliferation and microenvironment reprograming even when sterols are abundant. However, efficacy of targeting cholesterol metabolism for cancer treatment is always compromised. Here it is shown that CSN6 is elevated in HCC and is a positive regulator of hydroxymethylglutaryl-CoA synthase 1 (HMGCS1) of mevalonate (MVA) pathway to promote tumorigenesis. Mechanistically, CSN6 antagonizes speckle-type POZ protein (SPOP) ubiquitin ligase to stabilize HMGCS1, which in turn activates YAP1 to promote tumor growth. In orthotopic liver cancer models, targeting CSN6 and HMGCS1 hinders tumor growth in both normal and high fat diet. Significantly, HMGCS1 depletion improves YAP inhibitor efficacy in patient derived xenograft models. The results identify a CSN6-HMGCS1-YAP1 axis mediating tumor outgrowth in HCC and propose a therapeutic strategy of targeting non-alcoholic fatty liver diseases- associated HCC.}, }
@article {pmid38297837, year = {2024}, author = {Wang, SH and Zheng, T and Fawzi, NL}, title = {Structure and interactions of prion-like domains in transcription factor Efg1 phase separation.}, journal = {Biophysical journal}, volume = {123}, number = {11}, pages = {1481-1493}, pmid = {38297837}, issn = {1542-0086}, support = {R01 GM147677/GM/NIGMS NIH HHS/United States ; }, mesh = {*Protein Domains ; *Fungal Proteins/metabolism/chemistry/genetics ; Candida albicans/metabolism ; Prions/metabolism/chemistry ; Transcriptional Elongation Factors/metabolism/chemistry/genetics ; Transcription Factors/metabolism/chemistry/genetics ; Phase Separation ; DNA-Binding Proteins ; }, abstract = {Candida albicans, a prominent member of the human microbiome, can make an opportunistic switch from commensal coexistence to pathogenicity accompanied by an epigenetic shift between the white and opaque cell states. This transcriptional switch is under precise regulation by a set of transcription factors (TFs), with Enhanced Filamentous Growth Protein 1 (Efg1) playing a central role. Previous research has emphasized the importance of Efg1's prion-like domain (PrLD) and the protein's ability to undergo phase separation for the white-to-opaque transition of C. albicans. However, the underlying molecular mechanisms of Efg1 phase separation have remained underexplored. In this study, we delved into the biophysical basis of Efg1 phase separation, revealing the significant contribution of both N-terminal (N) and C-terminal (C) PrLDs. Through NMR structural analysis, we found that Efg1 N-PrLD and C-PrLD are mostly disordered but have prominent partial α-helical secondary structures in both domains. NMR titration experiments suggest that the partially helical structures in N-PrLD act as hubs for self-interaction as well as Efg1 interaction with RNA. Using condensed-phase NMR spectroscopy, we uncovered diverse amino acid interactions underlying Efg1 phase separation. Particularly, we highlight the indispensable role of tyrosine residues within the transient α-helical structures of PrLDs particularly in the N-PrLD compared to the C-PrLD in stabilizing phase separation. Our study provides evidence that the transient α-helical structure is present in the phase-separated state and highlights the particular importance of aromatic residues within these structures for phase separation. Together, these results enhance the understanding of C. albicans transcription factor interactions that lead to virulence and provide a crucial foundation for potential antifungal therapies targeting the transcriptional switch.}, }
@article {pmid38297075, year = {2024}, author = {Zhao, L and Cunningham, CM and Andruska, AM and Schimmel, K and Ali, MK and Kim, D and Gu, S and Chang, JL and Spiekerkoetter, E and Nicolls, MR}, title = {Rat microbial biogeography and age-dependent lactic acid bacteria in healthy lungs.}, journal = {Lab animal}, volume = {53}, number = {2}, pages = {43-55}, pmid = {38297075}, issn = {1548-4475}, support = {I01 BX005628/BX/BLRD VA/United States ; R01 HL095686/HL/NHLBI NIH HHS/United States ; R01 HL158714/HL/NHLBI NIH HHS/United States ; T32 HL098049/HL/NHLBI NIH HHS/United States ; }, mesh = {Humans ; Rats ; Animals ; Bacteria ; *Lactobacillales ; Lung/microbiology ; *Microbiota/genetics ; }, abstract = {The laboratory rat emerges as a useful tool for studying the interaction between the host and its microbiome. To advance principles relevant to the human microbiome, we systematically investigated and defined the multitissue microbial biogeography of healthy Fischer 344 rats across their lifespan. Microbial community profiling data were extracted and integrated with host transcriptomic data from the Sequencing Quality Control consortium. Unsupervised machine learning, correlation, taxonomic diversity and abundance analyses were performed to determine and characterize the rat microbial biogeography and identify four intertissue microbial heterogeneity patterns (P1-P4). We found that the 11 body habitats harbored a greater diversity of microbes than previously suspected. Lactic acid bacteria (LAB) abundance progressively declined in lungs from breastfed newborn to adolescence/adult, and was below detectable levels in elderly rats. Bioinformatics analyses indicate that the abundance of LAB may be modulated by the lung-immune axis. The presence and levels of LAB in lungs were further evaluated by PCR in two validation datasets. The lung, testes, thymus, kidney, adrenal and muscle niches were found to have age-dependent alterations in microbial abundance. The 357 microbial signatures were positively correlated with host genes in cell proliferation (P1), DNA damage repair (P2) and DNA transcription (P3). Our study established a link between the metabolic properties of LAB with lung microbiota maturation and development. Breastfeeding and environmental exposure influence microbiome composition and host health and longevity. The inferred rat microbial biogeography and pattern-specific microbial signatures could be useful for microbiome therapeutic approaches to human health and life quality enhancement.}, }
@article {pmid38293115, year = {2024}, author = {Zheludev, IN and Edgar, RC and Lopez-Galiano, MJ and de la Peña, M and Babaian, A and Bhatt, AS and Fire, AZ}, title = {Viroid-like colonists of human microbiomes.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {38293115}, issn = {2692-8205}, support = {R01 AI143757/AI/NIAID NIH HHS/United States ; R01 AI148623/AI/NIAID NIH HHS/United States ; R35 GM130366/GM/NIGMS NIH HHS/United States ; }, abstract = {Here, we describe the "Obelisks," a previously unrecognised class of viroid-like elements that we first identified in human gut metatranscriptomic data. "Obelisks" share several properties: (i) apparently circular RNA ~1kb genome assemblies, (ii) predicted rod-like secondary structures encompassing the entire genome, and (iii) open reading frames coding for a novel protein superfamily, which we call the "Oblins". We find that Obelisks form their own distinct phylogenetic group with no detectable sequence or structural similarity to known biological agents. Further, Obelisks are prevalent in tested human microbiome metatranscriptomes with representatives detected in ~7% of analysed stool metatranscriptomes (29/440) and in ~50% of analysed oral metatranscriptomes (17/32). Obelisk compositions appear to differ between the anatomic sites and are capable of persisting in individuals, with continued presence over >300 days observed in one case. Large scale searches identified 29,959 Obelisks (clustered at 90% nucleotide identity), with examples from all seven continents and in diverse ecological niches. From this search, a subset of Obelisks are identified to code for Obelisk-specific variants of the hammerhead type-III self-cleaving ribozyme. Lastly, we identified one case of a bacterial species (Streptococcus sanguinis) in which a subset of defined laboratory strains harboured a specific Obelisk RNA population. As such, Obelisks comprise a class of diverse RNAs that have colonised, and gone unnoticed in, human, and global microbiomes.}, }
@article {pmid38292856, year = {2023}, author = {Aguirre-García, MM and Amedei, A and Hernández-Ruiz, P and Gómez-García, AP and Niccolai, E and Moreno-Rodríguez, AM and Pinto-Cardoso, S and Alviter-Plata, A and Escalona-Montaño, AR and Ordaz-Robles, ER and González-Salazar, MDC and Springall Del Villar, R and Berrios-Bárcenas, EA and Ávila-Vanzzini, N}, title = {Cytokine and microbiota profiles in obesity-related hypertension patients.}, journal = {Frontiers in cellular and infection microbiology}, volume = {13}, number = {}, pages = {1325261}, pmid = {38292856}, issn = {2235-2988}, mesh = {Adult ; Humans ; Overweight/complications/microbiology ; Cytokines ; RNA, Ribosomal, 16S/genetics ; Cross-Sectional Studies ; Obesity/complications/microbiology ; Feces/microbiology ; *Gastrointestinal Microbiome/physiology ; *Hypertension/complications ; }, abstract = {BACKGROUND: Systemic arterial hypertension is linked to a heightened risk of cardiovascular diseases on a global scale. In Mexico, nearly half of adults in vulnerable conditions experience hypertension. Imbalance in the oral and intestinal microbiota composition has been observed in patients with hypertension, documented by a decrease of bacteria producing short-chain fatty acids, which play a critical role in blood pressure regulation.<br><br>AIM: To examine the cytokines' profile and assess the characteristics of oral and gut microbiota in obesity-related hypertension in Mexican patients.<br><br>METHODS: A cross-sectional, observational, and analytical study was carried out. Twenty-two patients were categorized by their body mass index (BMI) as overweight and obese, and the diagnosis of primary hypertension. DNA from supragingival dental plaque and feces samples was used to carry out 16S rRNA sequencing. Additionally, 13 cytokines were quantified.<br><br>RESULTS: In the oral microbiota, Kluyvera was found to be significantly enriched in obese compared to overweight patients. Instead, the gut microbiota was dominated by Firmicutes. However, the correlation between certain genera and proinflammatory cytokines was noted.<br><br>CONCLUSION: This exploratory study provides insights into the complex relationship between the oral and gut microbiota and their association with systemic inflammation in obesity-related hypertension.}, }
@article {pmid38292760, year = {2024}, author = {Candeliere, F and Sola, L and Raimondi, S and Rossi, M and Amaretti, A}, title = {Good and bad dispositions between archaea and bacteria in the human gut: New insights from metagenomic survey and co-occurrence analysis.}, journal = {Synthetic and systems biotechnology}, volume = {9}, number = {1}, pages = {88-98}, pmid = {38292760}, issn = {2405-805X}, abstract = {Archaea are an understudied component of the human microbiome. In this study, the gut archaeome and bacteriome of 60 healthy adults from different region were analyzed by whole-genome shotgun sequencing. Archaea were ubiquitously found in a wide range of abundances, reaching up to 7.2 %. The dominant archaeal phylum was Methanobacteriota, specifically the family Methanobacteriaceae, encompassing more than 50 % of Archaea in 50 samples. The previously underestimated Thermoplasmatota, mostly composed of Methanomassiliicoccaceae, dominated in 10 subjects (>50 %) and was present in all others except one. Halobacteriota, the sole other archaeal phylum, occurred in negligible concentration, except for two samples (4.6-4.8 %). This finding confirmed that the human gut archaeome is primarily composed of methanogenic organisms and among the known methanogenic pathway: i) hydrogenotrophic reduction of CO2 is the predominant, being the genus Methanobrevibacter and the species Methanobrevibacter smithii the most abundant in the majority of the samples; ii) the second pathway, that involved Methanomassiliicoccales, was the hydrogenotrophic reduction of methyl-compounds; iii) dismutation of acetate or methyl-compounds seemed to be absent. Co-occurrence analysis allowed to unravel correlations between Archaea and Bacteria that shapes the overall structure of the microbial community, allowing to depict a clearer picture of the human gut archaeome.}, }
@article {pmid38289047, year = {2024}, author = {Romani, L and Del Chierico, F and Pane, S and Ristori, MV and Pirona, I and Guarrasi, V and Cotugno, N and Bernardi, S and Lancella, L and Perno, CF and Rossi, P and Villani, A and Campana, A and Palma, P and Putignani, L and , }, title = {Exploring nasopharyngeal microbiota profile in children affected by SARS-CoV-2 infection.}, journal = {Microbiology spectrum}, volume = {12}, number = {3}, pages = {e0300923}, pmid = {38289047}, issn = {2165-0497}, support = {//Ministero della Salute (Italy Ministry of Health)/ ; 202003_Bioarte_Putignani//The BioArte Limited/ ; Current Research funds//Italian Ministry of Health/ ; }, mesh = {Adult ; Humans ; Child ; *COVID-19 ; RNA, Ribosomal, 16S/genetics ; SARS-CoV-2/genetics ; *Microbiota/genetics ; Nasopharynx ; Streptococcus/genetics ; }, abstract = {UNLABELLED: The relationship between COVID-19 and nasopharyngeal (NP) microbiota has been investigated mainly in the adult population. We explored the NP profile of children affected by COVID-19, compared to healthy controls (CTRLs). NP swabs of children with COVID-19, collected between March and September 2020, were investigated at the admission (T0), 72 h to 7 days (T1), and at the discharge (T2) of the patients. NP microbiota was analyzed by 16S rRNA targeted-metagenomics. Data from sequencing were investigated by QIIME 2.0 and PICRUSt 2. Multiple machine learning (ML) models were exploited to classify patients compared to CTRLs. The NP microbiota of COVID-19 patients (N = 71) was characterized by reduction of α-diversity compared to CTRLs (N = 59). The NP microbiota of COVID-19 cohort appeared significantly enriched in Streptococcus, Haemophilus, Staphylococcus, Veillonella, Enterococcus, Neisseria, Moraxella, Enterobacteriaceae, Gemella, Bacillus, and reduced in Faecalibacterium, Akkermansia, Blautia, Bifidobacterium, Ruminococcus, and Bacteroides, compared to CTRLs (FDR < 0.001). Exploiting ML models, Enterococcus, Pseudomonas, Streptococcus, Capnocytopagha, Tepidiphilus, Porphyromonas, Staphylococcus, and Veillonella resulted as NP microbiota biomarkers, in COVID-19 patients. No statistically significant differences were found comparing the NP microbiota profile of COVID-19 patients during the time-points or grouping patients on the basis of high, medium, and low viral load (VL). This evidence provides specific pathobiont signatures of the NP microbiota in pediatric COVID-19 patients, and the reduction of anaerobic protective commensals. Our data suggest that the NP microbiota may have a specific disease-related signature since infection onset without changes during disease progression, regardless of the SARS-CoV-2 VL.<br><br>IMPORTANCE: Since the beginning of pandemic, we know that children are less susceptible to severe COVID-19 disease. A potential role of the nasopharyngeal (NP) microbiota has been hypothesized but to date, most of the studies have been focused on adults. We studied the NP microbiota modifications in children affected by SARS-CoV-2 infection showing a specific NP microbiome profile, mainly composed by pathobionts and almost missing protective anaerobic commensals. Moreover, in our study, specific microbial signatures appear since the first days of infection independently from SARS-CoV-2 viral load.}, }
@article {pmid38287978, year = {2023}, author = {Rinaldi, F and Chirico, R and Trink, A and Pinto, D}, title = {Corrigendum: Resistance and pseudo-resistance to permethrin phenomena: the importance of controlling scabies.}, journal = {Frontiers in cellular and infection microbiology}, volume = {13}, number = {}, pages = {1358427}, doi = {10.3389/fcimb.2023.1358427}, pmid = {38287978}, issn = {2235-2988}, abstract = {[This corrects the article DOI: 10.3389/fcimb.2023.1297337.].}, }
@article {pmid38276099, year = {2024}, author = {Zerekidze, A and Li, M and Refisch, A and Shameya, J and Sobanski, T and Walter, M and Wagner, G}, title = {Impact of Toxoplasma gondii and Human Microbiome on Suicidal Behavior: A Systematic Review.}, journal = {Journal of clinical medicine}, volume = {13}, number = {2}, pages = {}, pmid = {38276099}, issn = {2077-0383}, support = {01EE2305F//Federal Ministry of Education and Research (Bundesministerium f&#xfc;r Bildung und Forschung [BMBF]) and the ministry of Th&#xfc;ringen within the initial phase of the German Center for Mental Health (DZPG)/ ; }, abstract = {BACKGROUND: Suicide remains a persistent global health challenge, resisting widespread prevention efforts. According to previous findings, toxoplasmosis is particularly associated with altered decision making, which could lead to risk-taking behavior, thereby increasing the likelihood for suicidal behavior (SB). In addition, discussion about the role of microbiome in psychiatric disorders has emerged lately, which also makes it relevant to investigate its role in the context of SB. Therefore, two systematic reviews are integrated in this paper, and the existing knowledge is comprehensively summarized regarding the association between microbial pathogens and SB.<br><br>METHODS: We conducted a systematic search with keywords including SB and Toxoplasma gondii (Suicid* AND Toxoplasm*) and microbiome (Suicid* AND Microbiome AND Microbiota) throughout PubMed and Scopus to retrieve related studies up to 9 November 2023, identifying 24 eligible records. The subjects of the included studies had to have fulfilled the criteria of an SB disorder as defined by DSM-5, and death cases needed to have been defined as suicide.<br><br>RESULTS: Most studies reported significant association between toxoplasmosis and SB, suggesting a higher likelihood of SB in the infected population. Regarding the microbiome, only very few studies investigated an association between SB and alterations in the microbiome. Based on six included studies, there were some indications of a link between changes in the microbiome and SB.<br><br>CONCLUSION: The cognitive aspects of decision making in T. gondii-infected individuals with SB should be further investigated to unravel the underlying mechanisms. Further sufficiently powered studies are needed to establish a link between SB and alterations in the microbiome.}, }
@article {pmid38274095, year = {2023}, author = {Roszczenko-Jasińska, P and Giełdoń, A and Mazur, D and Spodzieja, M and Plichta, M and Czaplewski, C and Bal, W and Jagusztyn-Krynicka, EK and Bartosik, D}, title = {Exploring the inhibitory potential of in silico-designed small peptides on Helicobacter pylori Hp0231 (DsbK), a periplasmic oxidoreductase involved in disulfide bond formation.}, journal = {Frontiers in molecular biosciences}, volume = {10}, number = {}, pages = {1335704}, pmid = {38274095}, issn = {2296-889X}, abstract = {Introduction: Helicobacter pylori is a bacterium that colonizes the gastric epithelium, which affects millions of people worldwide. H. pylori infection can lead to various gastrointestinal diseases, including gastric adenocarcinoma and mucosa-associated lymphoid tissue lymphoma. Conventional antibiotic therapies face challenges due to increasing antibiotic resistance and patient non-compliance, necessitating the exploration of alternative treatment approaches. In this study, we focused on Hp0231 (DsbK), an essential component of the H. pylori Dsb (disulfide bond) oxidative pathway, and investigated peptide-based inhibition as a potential therapeutic strategy. Methods: Three inhibitory peptides designed by computational modeling were evaluated for their effectiveness using a time-resolved fluorescence assay. We also examined the binding affinity between Hp0231 and the peptides using microscale thermophoresis. Results and discussion: Our findings demonstrate that in silico-designed synthetic peptides can effectively inhibit Hp0231-mediated peptide oxidation. Targeting Hp0231 oxidase activity could attenuate H. pylori virulence without compromising bacterial viability. Therefore, peptide-based inhibitors of Hp0231 could be candidates for the development of new targeted strategy, which does not influence the composition of the natural human microbiome, but deprive the bacterium of its pathogenic properties.}, }
@article {pmid38269610, year = {2024}, author = {Xuan, P and Gu, J and Cui, H and Wang, S and Toshiya, N and Liu, C and Zhang, T}, title = {Multi-scale topology and position feature learning and relationship-aware graph reasoning for prediction of drug-related microbes.}, journal = {Bioinformatics (Oxford, England)}, volume = {40}, number = {2}, pages = {}, pmid = {38269610}, issn = {1367-4811}, support = {62372282//Natural Science Foundation of China/ ; NTF22032//STU Scientific Research Initiation/ ; LH2023F044//Natural Science Foundation of Heilongjiang Province/ ; }, mesh = {Humans ; *Neural Networks, Computer ; *Semantics ; Software ; }, abstract = {MOTIVATION: The human microbiome may impact the effectiveness of drugs by modulating their activities and toxicities. Predicting candidate microbes for drugs can facilitate the exploration of the therapeutic effects of drugs. Most recent methods concentrate on constructing of the prediction models based on graph reasoning. They fail to sufficiently exploit the topology and position information, the heterogeneity of multiple types of nodes and connections, and the long-distance correlations among nodes in microbe-drug heterogeneous graph.<br><br>RESULTS: We propose a new microbe-drug association prediction model, NGMDA, to encode the position and topological features of microbe (drug) nodes, and fuse the different types of features from neighbors and the whole heterogeneous graph. First, we formulate the position and topology features of microbe (drug) nodes by t-step random walks, and the features reveal the topological neighborhoods at multiple scales and the position of each node. Second, as the features of nodes are high-dimensional and sparse, we designed an embedding enhancement strategy based on supervised fully connected autoencoders to form the embeddings with representative features and the more discriminative node distributions. Third, we propose an adaptive neighbor feature fusion module, which fuses features of neighbors by the constructed position- and topology-sensitive heterogeneous graph neural networks. A novel self-attention mechanism is developed to estimate the importance of the position and topology of each neighbor to a target node. Finally, a heterogeneous graph feature fusion module is constructed to learn the long-distance correlations among the nodes in the whole heterogeneous graph by a relationship-aware graph transformer. Relationship-aware graph transformer contains the strategy for encoding the connection relationship types among the nodes, which is helpful for integrating the diverse semantics of these connections. The extensive comparison experimental results demonstrate NGMDA's superior performance over five state-of-the-art prediction methods. The ablation experiment shows the contributions of the multi-scale topology and position feature learning, the embedding enhancement strategy, the neighbor feature fusion, and the heterogeneous graph feature fusion. Case studies over three drugs further indicate that NGMDA has ability in discovering the potential drug-related microbes.<br><br>Source codes and Supplementary Material are available at https://github.com/pingxuan-hlju/NGMDA.}, }
@article {pmid38268162, year = {2024}, author = {Park, JS}, title = {[Microbiome and Biliary Tract Cancer].}, journal = {The Korean journal of gastroenterology = Taehan Sohwagi Hakhoe chi}, volume = {83}, number = {1}, pages = {1-5}, doi = {10.4166/kjg.2023.135}, pmid = {38268162}, issn = {2233-6869}, mesh = {Humans ; Dysbiosis/complications ; *Biliary Tract Neoplasms/diagnosis/etiology ; *Biliary Tract ; *Gallbladder Diseases ; *Microbiota ; }, abstract = {Biliary tract cancers encompass a group of malignancies that affect the bile ducts and gallbladder and are associated with a poor prognosis, often due to late diagnosis and limited treatment options. The incidence of biliary tract cancer has been increasing gradually, underscoring the need for a better understanding of its pathogenesis and potential risk factors. Research suggests that biliary tract cancer may develop through a combination of genetic and epigenetic alterations, as well as environmental factors. The role of microbial exposure and the human microbiome in the pathogenesis of biliary tract cancer is an emerging area of interest. Traditionally, the biliary tree was considered sterile under normal conditions, but recent studies have identified associations between specific microbiological patterns and inflammatory biliary diseases and cancer. The human microbiome plays a crucial role in maintaining host homeostasis and interacting with the host's immune system. Dysbiosis, or an imbalance in the microbiome composition, has been implicated in the development of various diseases, including cancer. Hence, dysbiosis in the biliary tract might trigger the pathogenesis of biliary tract cancer. Advances in next-generation sequencing technology have provided researchers with a more comprehensive view of the microbiota and their potential roles in health and disease, providing more evidence of the relationship between the microbiota and biliary tract cancer. This review summarizes the latest evidence of the microbiome that would be associated with biliary tract cancer.}, }
@article {pmid38264887, year = {2024}, author = {Inglis, LK and Roach, MJ and Edwards, RA}, title = {Prophages: an integral but understudied component of the human microbiome.}, journal = {Microbial genomics}, volume = {10}, number = {1}, pages = {}, pmid = {38264887}, issn = {2057-5858}, support = {RC2 DK116713/DK/NIDDK NIH HHS/United States ; }, mesh = {Humans ; Prophages ; *Bacteriophages ; Genome, Bacterial ; *Microbiota ; DNA ; }, abstract = {Phages integrated into a bacterial genome - called prophages - continuously monitor the vigour of the host bacteria to determine when to escape the genome and to protect their host from other phage infections, and they may provide genes that promote bacterial growth. Prophages are essential to almost all microbiomes, including the human microbiome. However, most human microbiome studies have focused on bacteria, ignoring free and integrated phages, so we know little about how these prophages affect the human microbiome. To address this gap in our knowledge, we compared the prophages identified in 14 987 bacterial genomes isolated from human body sites to characterize prophage DNA in the human microbiome. Here, we show that prophage DNA is ubiquitous, comprising on average 1-5 % of each bacterial genome. The prophage content per genome varies with the isolation site on the human body, the health of the human and whether the disease was symptomatic. The presence of prophages promotes bacterial growth and sculpts the microbiome. However, the disparities caused by prophages vary throughout the body.}, }
@article {pmid38259963, year = {2023}, author = {Rubio-Garcia, E and Ferrando, N and Martin, N and Ballesté-Delpierre, C and Miró, JM and Paredes, R and Casals-Pascual, C and Vila, J}, title = {In vitro antibacterial activity of antiretroviral drugs on key commensal bacteria from the human microbiota.}, journal = {Frontiers in cellular and infection microbiology}, volume = {13}, number = {}, pages = {1306430}, pmid = {38259963}, issn = {2235-2988}, mesh = {Female ; Humans ; *HIV Infections/drug therapy ; *Methicillin-Resistant Staphylococcus aureus ; *Microbiota ; Bacteria ; Anti-Retroviral Agents/pharmacology ; Anti-Bacterial Agents/pharmacology ; }, abstract = {INTRODUCTION: Antiretroviral therapy has improved life expectancy in HIV-infected patients. However, people living with HIV under antiretroviral therapy are at higher risks of developing chronic complications and acquiring multidrug resistant bacteria than healthy population. These factors have been associated with shifts in gut microbiome composition and immune activation. It is unclear how antiretroviral drugs affect gut microbiota composition, but it has been observed that antiretroviral treatment is not able to fully restore gut health after HIV infection. Additionally, some antiretroviral drugs have shown antibacterial activity suggesting that these drugs could have a direct impact on the human microbiome composition.<br><br>METHODS: We determined the in vitro antibacterial activity of 16 antiretroviral drugs against a set of key clinically relevant and human commensal bacterial strains.<br><br>RESULTS: Our results demonstrate that 5 antiretroviral drugs have in vitro antibacterial activity against gut and vaginal human commensal bacteria. Zidovudine has antibacterial activity against Escherichia coli, Klebsiella pneumoniae and Prevotella bivia, abacavir against Gardnerella vaginalis, efavirenz against G. vaginalis and P. bivia and bictegravir against Enterococcus spp. and G. vaginalis. Moreover, we describe for the first time that elvitegravir has antibacterial activity against G. vaginalis and P. bivia and, most importantly, against vancomycin-resistant Enterococcus spp. and methicillin-resistant Staphylococcus aureus strains with MIC values of 4-16 and 4 &#xb5;g/mL, respectively showing high level of effectiveness against the tested multidrug-resistant bacteria.<br><br>DISCUSSION: Our results underscore that some antiretroviral drugs may influence the human microbiota composition. In addition, we report the potential use of elvitegravir to treat multidrug-resistant Gram-positive bacteria warranting the need of clinical studies to repurpose this antiretroviral drug.}, }
@article {pmid38257864, year = {2023}, author = {Marsiglia, R and Marangelo, C and Vernocchi, P and Scanu, M and Pane, S and Russo, A and Guanziroli, E and Del Chierico, F and Valeriani, M and Molteni, F and Putignani, L}, title = {Gut Microbiota Ecological and Functional Modulation in Post-Stroke Recovery Patients: An Italian Study.}, journal = {Microorganisms}, volume = {12}, number = {1}, pages = {}, pmid = {38257864}, issn = {2076-2607}, abstract = {Ischemic stroke (IS) can be caused by perturbations of the gut-brain axis. An imbalance in the gut microbiota (GM), or dysbiosis, may be linked to several IS risk factors and can influence the brain through the production of different metabolites, such as short-chain fatty acids (SCFAs), indole and derivatives. This study examines ecological changes in the GM and its metabolic activities after stroke. Fecal samples of 10 IS patients were compared to 21 healthy controls (CTRLs). GM ecological profiles were generated via 16S rRNA taxonomy as functional profiles using metabolomics analysis performed with a gas chromatograph coupled to a mass spectrometer (GC-MS). Additionally fecal zonulin, a marker of gut permeability, was measured using an enzyme-linked immuno assay (ELISA). Data were analyzed using univariate and multivariate statistical analyses and correlated with clinical features and biochemical variables using correlation and nonparametric tests. Metabolomic analyses, carried out on a subject subgroup, revealed a high concentration of fecal metabolites, such as SCFAs, in the GM of IS patients, which was corroborated by the enrichment of SCFA-producing bacterial genera such as Bacteroides, Christensellaceae, Alistipes and Akkermansia. Conversely, indole and 3-methyl indole (skatole) decreased compared to a subset of six CTRLs. This study illustrates how IS might affect the gut microbial milieu and may suggest potential microbial and metabolic biomarkers of IS. Expanded populations of Akkermansia and enrichment of acetic acid could be considered potential disease phenotype signatures.}, }
@article {pmid38256183, year = {2024}, author = {Filippou, C and Themistocleous, SC and Marangos, G and Panayiotou, Y and Fyrilla, M and Kousparou, CA and Pana, ZD and Tsioutis, C and Johnson, EO and Yiallouris, A}, title = {Microbial Therapy and Breast Cancer Management: Exploring Mechanisms, Clinical Efficacy, and Integration within the One Health Approach.}, journal = {International journal of molecular sciences}, volume = {25}, number = {2}, pages = {}, pmid = {38256183}, issn = {1422-0067}, mesh = {Animals ; Humans ; *One Health ; Treatment Outcome ; Estrogens ; Cognition ; *Neoplasms ; }, abstract = {This comprehensive review elucidates the profound relationship between the human microbiome and breast cancer management. Recent findings highlight the significance of microbial alterations in tissue, such as the gut and the breast, and their role in influencing the breast cancer risk, development, progression, and treatment outcomes. We delve into how the gut microbiome can modulate systemic inflammatory responses and estrogen levels, thereby impacting cancer initiation and therapeutic drug efficacy. Furthermore, we explore the unique microbial diversity within breast tissue, indicating potential imbalances brought about by cancer and highlighting specific microbes as promising therapeutic targets. Emphasizing a holistic One Health approach, this review underscores the importance of integrating insights from human, animal, and environmental health to gain a deeper understanding of the complex microbe-cancer interplay. As the field advances, the strategic manipulation of the microbiome and its metabolites presents innovative prospects for the enhancement of cancer diagnostics and therapeutics. However, rigorous clinical trials remain essential to confirm the potential of microbiota-based interventions in breast cancer management.}, }
@article {pmid38256159, year = {2024}, author = {Rezzani, R and Gianò, M and Pinto, D and Rinaldi, F and van Noorden, CJF and Favero, G}, title = {Hepatic Alterations in a BTBR T + Itpr3tf/J Mouse Model of Autism and Improvement Using Melatonin via Mitigation Oxidative Stress, Inflammation and Ferroptosis.}, journal = {International journal of molecular sciences}, volume = {25}, number = {2}, pages = {}, pmid = {38256159}, issn = {1422-0067}, support = {ARRS P1-0245//Slovenian Research Agency/ ; J3-2526//Slovenian Research Agency/ ; }, mesh = {Humans ; Animals ; Mice ; *Autistic Disorder/drug therapy/genetics ; Kelch-Like ECH-Associated Protein 1 ; *Melatonin/pharmacology/therapeutic use ; *Autism Spectrum Disorder/drug therapy/genetics ; *Ferroptosis ; NF-E2-Related Factor 2/genetics ; Liver ; Inflammation/drug therapy ; Oxidative Stress ; Disease Models, Animal ; Mice, Inbred C57BL ; }, abstract = {Autism spectrum disorder (ASD) is a complicated neurodevelopmental disorder, and its etiology is not well understood. It is known that genetic and nongenetic factors determine alterations in several organs, such as the liver, in individuals with this disorder. The aims of the present study were to analyze morphological and biological alterations in the liver of an autistic mouse model, BTBR T + Itpr3tf/J (BTBR) mice, and to identify therapeutic strategies for alleviating hepatic impairments using melatonin administration. We studied hepatic cytoarchitecture, oxidative stress, inflammation and ferroptosis in BTBR mice and used C57BL6/J mice as healthy control subjects. The mice were divided into four groups and then treated and not treated with melatonin, respectively. BTBR mice showed (a) a retarded development of livers and (b) iron accumulation and elevated oxidative stress and inflammation. We demonstrated that the expression of ferroptosis markers, the transcription factor nuclear factor erythroid-related factor 2 (NFR2), was upregulated, and the Kelch-like ECH-associated protein 1 (KEAP1) was downregulated in BTBR mice. Then, we evaluated the effects of melatonin on the hepatic alterations of BTBR mice; melatonin has a positive effect on liver cytoarchitecture and metabolic functions.}, }
@article {pmid38249228, year = {2023}, author = {Bhattacharjee, P and Karim, KA and Khan, Z}, title = {Harnessing the Microbiome: A Comprehensive Review on Advancing Therapeutic Strategies for Rheumatic Diseases.}, journal = {Cureus}, volume = {15}, number = {12}, pages = {e50964}, pmid = {38249228}, issn = {2168-8184}, abstract = {Rheumatic diseases are a group of disorders that affect the joints, muscles, and bones. These diseases, such as rheumatoid arthritis, lupus, and psoriatic arthritis, can cause pain, stiffness, and swelling, leading to reduced mobility and disability. Recent studies have identified the microbiome, the diverse community of microorganisms that live in and on the human body, as a potential factor in the development and progression of rheumatic diseases. Harnessing the microbiome offers a promising new avenue for developing therapeutic strategies for these debilitating conditions. There is growing interest in the role of oral and gut microbiomes in the management of rheumatoid arthritis and other autoimmune disease. Microbial metabolites have immunomodulatory properties that could be exploited for rheumatic disorders. A wide range of microorganisms are present in the oral cavity and are found to be vulnerable to the effects of the environment. The physiology and ecology of the microbiota become intimately connected with those of the host, and they critically influence the promotion of health or progression toward disease. This article aims to provide a comprehensive overview of the current state of knowledge on oral and gut microbiome and its potential future role in the management of rheumatic diseases. This article will also discuss newer treatment strategies such as bioinformatic analyses and fecal transplantation.}, }
@article {pmid38247937, year = {2024}, author = {Kim, J and Jang, H and Koh, H}, title = {MiMultiCat: A Unified Cloud Platform for the Analysis of Microbiome Data with Multi-Categorical Responses.}, journal = {Bioengineering (Basel, Switzerland)}, volume = {11}, number = {1}, pages = {}, pmid = {38247937}, issn = {2306-5354}, support = {2021R1C1C1013861//National Research Foundation of Korea/ ; }, abstract = {The field of the human microbiome is rapidly growing due to the recent advances in high-throughput sequencing technologies. Meanwhile, there have also been many new analytic pipelines, methods and/or tools developed for microbiome data preprocessing and analytics. They are usually focused on microbiome data with continuous (e.g., body mass index) or binary responses (e.g., diseased vs. healthy), yet multi-categorical responses that have more than two categories are also common in reality. In this paper, we introduce a new unified cloud platform, named MiMultiCat, for the analysis of microbiome data with multi-categorical responses. The two main distinguishing features of MiMultiCat are as follows: First, MiMultiCat streamlines a long sequence of microbiome data preprocessing and analytic procedures on user-friendly web interfaces; as such, it is easy to use for many people in various disciplines (e.g., biology, medicine, public health). Second, MiMultiCat performs both association testing and prediction modeling extensively. For association testing, MiMultiCat handles both ecological (e.g., alpha and beta diversity) and taxonomical (e.g., phylum, class, order, family, genus, species) contexts through covariate-adjusted or unadjusted analysis. For prediction modeling, MiMultiCat employs the random forest and gradient boosting algorithms that are well suited to microbiome data while providing nice visual interpretations. We demonstrate its use through the reanalysis of gut microbiome data on obesity with body mass index categories. MiMultiCat is freely available on our web server.}, }
@article {pmid38247589, year = {2023}, author = {Garba, Z and Kaboré, B and Bonkoungou, IJO and Natama, MH and Rouamba, T and Haukka, K and Kirveskari, JP and Tinto, H and Sangaré, L and Barro, N and Kantele, A}, title = {Phenotypic Detection of Carbapenemase and AmpC-β-Lactamase Production among Extended Spectrum β-Lactamase (ESBL)-Producing Escherichia coli and Klebsiella spp. Isolated from Clinical Specimens.}, journal = {Antibiotics (Basel, Switzerland)}, volume = {13}, number = {1}, pages = {}, pmid = {38247589}, issn = {2079-6382}, support = {FA4-DGD program//Belgium Directorate General for Development Cooperation (DGD) through the collaborative framework agreement 4 between Clinical Research Unit of Nanoro (CRUN), Burkina Faso and Institute of Tropical Medicine of Antwerp (ITM), Belgium and the Academy of Fin/ ; 318642//Academy of Finland through the AMRIWA project/ ; //Finnish institutions (FinELib)/ ; }, abstract = {Introduction: Data on antimicrobial resistance (AMR) are sparse across numerous African countries, as microbiological analyses are not routinely conducted and surveillance data are not collected. Accordingly, clinical samples are not routinely tested for carbapenem-resistant bacteria and, therefore, the general understanding of their prevalence in the region remains limited. Methods: Between January 2020 and June 2022, we collected extended spectrum β-lactamase (ESBL)-producing Enterobacterales (ESBL-PE) isolates from five hospitals in Burkina Faso. After an initial culture on ESBL-selective media, the species were identified using API20E and isolates were tested against 13 antimicrobial agents using the disc diffusion method on Mueller-Hinton (MH) agar. ESBL production was confirmed via a double-disc synergy test. Production of carbapenemases and AmpC-β-lactamases and phenotypic co-resistance were determined. Results: Among the 473 ESBL-PE, 356 were ESBL-E. coli (ESBL-Ec) and 117 were Klebsiella spp. (ESBL-K). Of these isolates, 5.3% were carbapenemase and 5.3% were AmpC-β-lactamase-positive. Three types of carbapenemases were identified: 19 NDM, 3 OXA-48-like and 1 VIM. Two isolates produced both NDM and OXA-48-like carbapenemases. Carbapenemase producers were detected at all levels of healthcare. Co-resistance rates were up to 85% for aminoglycosides, 90% for sulfonamides, 95% for fluoroquinolones and 25% for chloramphenicol. Fosfomycin resistance was 6% for ESBL-Ec and 49% for ESBL-K (49%). Conclusions: Some of the ESBL-Ec and ESBL-K co-produced carbapenemases and/or AmpC-β-lactamases at all healthcare levels and in various sample types with high co-resistance rates to non-betalactams. Carbapenem resistance is no longer rare, calling for testing in routine diagnostics, a comprehensive resistance surveillance system and infection control within healthcare.}, }
@article {pmid38246848, year = {2024}, author = {Liu, Y and Fachrul, M and Inouye, M and Méric, G}, title = {Harnessing human microbiomes for disease prediction.}, journal = {Trends in microbiology}, volume = {32}, number = {7}, pages = {707-719}, doi = {10.1016/j.tim.2023.12.004}, pmid = {38246848}, issn = {1878-4380}, support = {RG/18/13/33946/BHF_/British Heart Foundation/United Kingdom ; }, mesh = {Humans ; *Microbiota ; Risk Factors ; Cardiovascular Diseases/microbiology ; }, abstract = {The human microbiome has been increasingly recognized as having potential use for disease prediction. Predicting the risk, progression, and severity of diseases holds promise to transform clinical practice, empower patient decisions, and reduce the burden of various common diseases, as has been demonstrated for cardiovascular disease or breast cancer. Combining multiple modifiable and non-modifiable risk factors, including high-dimensional genomic data, has been traditionally favored, but few studies have incorporated the human microbiome into models for predicting the prospective risk of disease. Here, we review research into the use of the human microbiome for disease prediction with a particular focus on prospective studies as well as the modulation and engineering of the microbiome as a therapeutic strategy.}, }
@article {pmid38246133, year = {2024}, author = {Chulenbayeva, L and Ganzhula, Y and Kozhakhmetov, S and Jarmukhanov, Z and Nurgaziyev, M and Nurgozhina, A and Muhanbetzhanov, N and Sergazy, S and Zhetkenev, S and Borykbay, Z and Tkachev, V and Urazova, S and Vinogradova, E and Kushugulova, A}, title = {The Trajectory of Successful Aging: Insights from Metagenome and Cytokine Profiling.}, journal = {Gerontology}, volume = {70}, number = {4}, pages = {390-407}, pmid = {38246133}, issn = {1423-0003}, mesh = {Aged, 80 and over ; Humans ; *Metagenome ; Aging ; *Microbiota ; Longevity ; Cytokines ; }, abstract = {INTRODUCTION: The longevity is influenced by genetic, environmental, and lifestyle factors. The specific changes that occur in the gut microbiome during the aging process, and their relationship to longevity and immune function, have not yet been fully understood. The ongoing research of other microbiome based on longevity cohort in Kazakhstan provides preliminary information on longevity-related aging, where cytokine expression is associated with specific microbial communities and microbial functions.<br><br>METHODS: Metagenomic shotgun sequencing study of 40 long-lived individuals aged 90 years and over was carried out, who were conditionally healthy and active, able to serve themselves, without a history of serious infection and cancer, who had not taken any antimicrobials, including probiotics. Blood serum was analyzed for clinical and laboratory characteristics. The cytokine and chemokine profile in serum and stool samples was assessed using multiplex analysis.<br><br>RESULTS: We found a significant increase in the expression of pro-inflammatory cytokines IL-1a, IL-6, 12p70, IP-10, IFN&#x3b1;2, IL-15, TNFa, as well as chemokines MIP-1a/CCL3 and MIP-1b/CCL4, chemokine motif ligands MCP-3/CCL7 and MDC/CCL22(1c). Nonagenerians and centenarians demonstrated a greater diversity of core microbiota genera and showed an elevated prevalence of the genera Bacteroides, Clostridium, Escherichia, and Alistipes. Conversely, there was a decrease in the abundance of the genera Ruminococcus, Fusicatenibacter, Dorea, as well as the species Fusicatenibacter saccharivorans. Furthermore, functional analysis revealed that the microbiome in long-lived group has a high capacity for lipid metabolism, amino acid degradation, and potential signs of chronic inflammatory status.<br><br>CONCLUSION: Long-lived individuals exhibit an immune system imbalance and observed changes in the composition of the gut microbiota at the genus level between to the two age-groups. Age-related changes in the gut microbiome, metabolic functions of the microbial community, and chronic inflammation all contribute to immunosenescence. In turn, the inflammatory state and microbial composition of the gut is related to nutritional status.}, }
@article {pmid38243767, year = {2024}, author = {Zudock, KK and Player, R and Ernlund, A and Timm, CM and English, CE and Ellis, MW and Tribble, DR and Merrell, DS and Bennett, JW and Millar, EV}, title = {Dynamics of the Oral Microbiome During Initial Military Training at Fort Benning, Georgia.}, journal = {Military medicine}, volume = {189}, number = {7-8}, pages = {e1753-e1759}, pmid = {38243767}, issn = {1930-613X}, support = {IAA Y1-Al-5072//Division of Intramural Research, National Institute of Allergy and Infectious Diseases/ ; HU0001190002//Defense Health Agency/ ; }, mesh = {Humans ; *Microbiota/physiology ; Male ; *Military Personnel/statistics &amp; numerical data ; Female ; Cohort Studies ; Georgia/epidemiology ; Mouth/microbiology ; RNA, Ribosomal, 16S/analysis ; }, abstract = {INTRODUCTION: Military trainees are at increased risk for infectious disease outbreaks because of the unique circumstances of the training environment (e.g., close proximity areas and physiologic/psychologic stress). Standard medical countermeasures in military training settings include routine immunization (e.g., influenza and adenovirus) as well as chemoprophylaxis [e.g., benzathine penicillin G (Bicillin) for the prevention of group A streptococcal disease] for pathogens associated with outbreaks in these settings. In a population of U.S. Army Infantry trainees, we evaluated changes in the oral microbiome during a 14-week military training cycle.<br><br>MATERIALS AND METHODS: Trainees were enrolled in an observational cohort study in 2015-2016. In 2015, Bicillin was administered to trainees to ameliorate the risk of group A Streptococcus outbreaks, whereas in 2016, trainees did not receive a Bicillin inoculation. Oropharyngeal swabs were collected from participants at days 0, 7, 14, 28, 56, and 90 of training. Swabs were collected, flash frozen, and stored. DNA was extracted from swabs, and amplicon sequencing of the 16s rRNA gene was performed. Microbiome dynamics were evaluated using the QIIME 2 workflow along with DADA2, SINA with SILVA, and an additional processing in R.<br><br>RESULTS: We observed that microbiome samples from the baseline (day 0) visit were distinct from one another, whereas samples collected on day 14 exhibited significant microbiome convergence. Day 14 convergence was coincident with an increase in DNA sequences associated with Streptococcus, though there was not a significant difference between Streptococcus abundance over time between 2015 and 2016 (P&#x2009;=&#x2009;.07), suggesting that Bicillin prophylaxis did not significantly impact overall Streptococcus abundance.<br><br>CONCLUSIONS: The temporary convergence of microbiomes is coincident with a rise in communicable infections in this population. The dynamic response of microbiomes during initial military training supports similar observations in the literature of transient convergence of the human microbiome under cohabitation in the time frame including in this experiment. This population and the associated longitudinal studies allow for controlled studies of human microbiome under diverse conditions.}, }
@article {pmid38239365, year = {2023}, author = {Kim, S and Chun, SH and Cheon, YH and Kim, M and Kim, HO and Lee, H and Hong, ST and Park, SJ and Park, MS and Suh, YS and Lee, SI}, title = {Peptoniphilus gorbachii alleviates collagen-induced arthritis in mice by improving intestinal homeostasis and immune regulation.}, journal = {Frontiers in immunology}, volume = {14}, number = {}, pages = {1286387}, pmid = {38239365}, issn = {1664-3224}, mesh = {Mice ; Humans ; Animals ; *Arthritis, Experimental ; *Arthritis, Rheumatoid ; Disease Models, Animal ; Cytokines/metabolism ; *Firmicutes ; }, abstract = {INTRODUCTION: The intricate connection between gut microbiota and rheumatoid arthritis (RA) pathogenesis has gained prominence, although the specific microbial species contributing to RA development remain largely unknown. Recent studies have sought to comprehensively explore alterations in the human microbiome, focusing on identifying disease-related microbial species through blood analysis. Consequently, this study aimed to identify RA-associated microbial species using a serum microbial array system and to investigate the efficacy and underlying mechanisms of potential microbial species for RA treatment.<br><br>METHODS: Serum immunoglobulin M levels against 384 intestinal microbial species were assessed using a microbial microarray in patients with RA and healthy individuals. We investigated the therapeutic potential of the identified microbial candidate regarding arthritis development, immune responses, gut barrier function, and gut microbiome using a collagen-induced arthritis (CIA) mouse model.<br><br>RESULTS: Our findings revealed significant alterations in antibody levels against 36 microbial species in patients with RA compared to healthy individuals. Notably, the antibody levels against Peptoniphilus gorbachii (PG) were decreased in patients with RA and exhibited an inverse correlation with RA disease activity. In vitro experiments demonstrated that PG produced acetate and butyrate, while exhibiting anti-inflammatory properties. In CIA mice, PG administration suppressed arthritis symptoms, reduced the accumulation of inflammatory monocytes in the mesenteric lymph nodes, and downregulated gene expression of pro-inflammatory cytokines in the ileum. Additionally, PG supplementation restored intestinal barrier integrity and partially resolved gut microbial dysbiosis in CIA mice. The fecal microbiota in PG-treated mice corresponded to improved intestinal barrier integrity and reduced inflammatory responses.<br><br>CONCLUSION: This study highlights the potential of serum-based detection of anti-microbial antibodies to identify microbial targets at the species level for RA treatment. Moreover, our findings suggest that PG, identified through the microbial microarray analysis, holds therapeutic potential for RA by restoring intestinal barrier integrity and suppressing the immunologic response associated with RA.}, }
@article {pmid38235259, year = {2024}, author = {Zhang, G and Le Souëf, P}, title = {The influence of modern living conditions on the human microbiome and potential therapeutic opportunities for allergy prevention.}, journal = {The World Allergy Organization journal}, volume = {17}, number = {1}, pages = {100857}, pmid = {38235259}, issn = {1939-4551}, abstract = {Modern living conditions and the recent surge in global urbanization have transformed the human microbiome. This transformation is believed to be a significant factor in the recent spike of common chronic inflammatory diseases like asthma and allergies worldwide, evident in both developed and developing nations. Immigrants from less developed regions who settle in highly urbanized and affluent areas present an ideal demographic for research. Investigating immigrant populations can yield valuable insights, particularly when studying microbiome changes that occur as individuals transition from areas with low asthma prevalence to regions with a high prevalence of the condition. The application of prebiotics and probiotics as potential treatments for asthma and allergies faces challenges. This is due to the complex interplay of numerous factors that contribute to their aetiology. Exploring the interaction between the human microbiome and potential epigenetic changes in specific populations, such as immigrants adapting to new, urbanized environments, may offer crucial insights. Such research could underscore the role of prebiotics and probiotics in preventing allergic conditions. Recognizing the changes in the human microbiome in the context of a Western/modern environment might be essential in addressing the increasing prevalence of allergic diseases. Persistent research in this domain is pivotal for devising effective interventions such as dietary supplementation with prebiotics and probiotics.}, }
@article {pmid38233502, year = {2024}, author = {Chopra, A and Franco-Duarte, R and Rajagopal, A and Choowong, P and Soares, P and Rito, T and Eberhard, J and Jayasinghe, TN}, title = {Exploring the presence of oral bacteria in non-oral sites of patients with cardiovascular diseases using whole metagenomic data.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {1476}, pmid = {38233502}, issn = {2045-2322}, support = {2022.00340.CEECIND//Funda&#xe7;&#xe3;o para a Ci&#xea;ncia e a Tecnologia/ ; "Contrato-Programa" UIDB/04050/2020//Funda&#xe7;&#xe3;o para a Ci&#xea;ncia e a Tecnologia/ ; }, mesh = {Humans ; *Cardiovascular Diseases ; *Microbiota/genetics ; Bacteria/genetics ; Metagenome ; *Plaque, Atherosclerotic ; }, abstract = {Cardiovascular diseases (CVDs) encompass various conditions affecting the heart and its blood vessels and are often linked with oral microbes. Our data analysis aimed to identify oral bacteria from other non-oral sites (i.e., gut, arterial plaque and cultured blood) that could be linked with CVDs. Taxonomic profiling identified bacteria to the species level and compared with the Human Oral Microbiome Database (HOMD). The oral bacteria in the gut, cultured blood and arterial plaque samples were catalogued, with their average frequency calculated for each sample. Additionally, data were filtered by comparison with the Human Microbiome Project (HMP) database. We identified 17,243 microbial species, of which 410 were present in the HOMD database and further denominated as "oral", and were found in at least one gut sample, but only 221 and 169 species were identified in the cultured blood and plaque samples, respectively. Of the 410 species, 153 were present solely in oral-associated environments after comparison with the HMP database, irrespective of their presence in other body sites. Our results suggest a potential connection between the presence of specific species of oral bacterial and occurrence of CVDs. Detecting these oral bacterial species in non-oral sites of patients with CVDs could help uncover the link between oral health and general health, including cardiovascular conditions via bacterial translocation.}, }
@article {pmid38229087, year = {2024}, author = {Federico, A and Möbus, L and Al-Abdulraheem, Z and Pavel, A and Fortino, V and Del Giudice, G and Alenius, H and Fyhrquist, N and Greco, D}, title = {Integrative network analysis suggests prioritised drugs for atopic dermatitis.}, journal = {Journal of translational medicine}, volume = {22}, number = {1}, pages = {64}, pmid = {38229087}, issn = {1479-5876}, support = {101043848//HORIZON EUROPE European Research Council/ ; 322761//Academy of Finland/ ; 821511//HORIZON EUROPE Innovative Medicines Initiative 2 Joint Undertaking (JU)/ ; }, mesh = {Humans ; *Dermatitis, Atopic/drug therapy/genetics ; Skin ; Gene Expression Profiling ; Phenotype ; Biomarkers ; }, abstract = {BACKGROUND: Atopic dermatitis (AD) is a prevalent chronic inflammatory skin disease whose pathophysiology involves the interplay between genetic and environmental factors, ultimately leading to dysfunction of the epidermis. While several treatments are effective in symptom management, many existing therapies offer only temporary relief and often come with side effects. For this reason, the formulation of an effective therapeutic plan is challenging and there is a need for more effective and targeted treatments that address the root causes of the condition. Here, we hypothesise that modelling the complexity of the molecular buildup of the atopic dermatitis can be a concrete means to drive drug discovery.<br><br>METHODS: We preprocessed, harmonised and integrated publicly available transcriptomics datasets of lesional and non-lesional skin from AD patients. We inferred co-expression network models of both AD lesional and non-lesional skin and exploited their interactional properties by integrating them with a priori knowledge in order to extrapolate a robust AD disease module. Pharmacophore-based virtual screening was then utilised to build a tailored library of compounds potentially active for AD.<br><br>RESULTS: In this study, we identified a core disease module for AD, pinpointing known and unknown molecular determinants underlying the skin lesions. We identified skin- and immune-cell type signatures expressed by the disease module, and characterised the impaired cellular functions underlying the complex phenotype of atopic dermatitis. Therefore, by investigating the connectivity of genes belonging to the AD module, we prioritised novel putative biomarkers of the disease. Finally, we defined a tailored compound library by characterising the therapeutic potential of drugs targeting genes within the disease module to facilitate and tailor future drug discovery efforts towards novel pharmacological strategies for AD.<br><br>CONCLUSIONS: Overall, our study reveals a core disease module providing unprecedented information about genetic, transcriptional and pharmacological relationships that foster drug discovery in atopic dermatitis.}, }
@article {pmid38228159, year = {2024}, author = {Nenciarini, S and Renzi, S and di Paola, M and Meriggi, N and Cavalieri, D}, title = {Ascomycetes yeasts: The hidden part of human microbiome.}, journal = {WIREs mechanisms of disease}, volume = {16}, number = {3}, pages = {e1641}, doi = {10.1002/wsbm.1641}, pmid = {38228159}, issn = {2692-9368}, support = {G84I18000160002//Regione Toscana/ ; 36954/7303/18//Ministero delle Politiche Agricole Alimentari e Forestali/ ; 529051018//Joint Programming Initiative A healthy diet for a healthy life/ ; JTC-2017-7//Joint Programming Initiative A healthy diet for a healthy life/ ; }, mesh = {Humans ; *Ascomycota/genetics ; Mycobiome/genetics ; Microbiota ; Metagenomics/methods ; Candida/genetics/isolation &amp; purification ; Gastrointestinal Microbiome ; }, abstract = {The fungal component of the microbiota, the mycobiota, has been neglected for a long time due to its poor richness compared to bacteria. Limitations in fungal detection and taxonomic identification arise from using metagenomic approaches, often borrowed from bacteriome analyses. However, the relatively recent discoveries of the ability of fungi to modulate the host immune response and their involvement in human diseases have made mycobiota a fundamental component of the microbial communities inhabiting the human host, deserving some consideration in host-microbe interaction studies and in metagenomics. Here, we reviewed recent data on the identification of yeasts of the Ascomycota phylum across human body districts, focusing on the most representative genera, that is, Saccharomyces and Candida. Then, we explored the key factors involved in shaping the human mycobiota across the lifespan, ranging from host genetics to environment, diet, and lifestyle habits. Finally, we discussed the strengths and weaknesses of culture-dependent and independent methods for mycobiota characterization. Overall, there is still room for some improvements, especially regarding fungal-specific methodological approaches and bioinformatics challenges, which are still critical steps in mycobiota analysis, and to advance our knowledge on the role of the gut mycobiota in human health and disease. This article is categorized under: Immune System Diseases > Genetics/Genomics/Epigenetics Immune System Diseases > Environmental Factors Infectious Diseases > Environmental Factors.}, }
@article {pmid38227345, year = {2024}, author = {Grasso, G and Bianciotto, V and Marmeisse, R}, title = {Paleomicrobiology: Tracking the past microbial life from single species to entire microbial communities.}, journal = {Microbial biotechnology}, volume = {17}, number = {1}, pages = {e14390}, pmid = {38227345}, issn = {1751-7915}, support = {//Alliance Sorbonne Universit&#xe9;/ ; ATM 2021//Mus&#xe9;um National d'Histoire Naturelle/ ; Bando Da Vinci 2022//Universit&#xe0; Italo Francese/ ; }, mesh = {Humans ; *Microbiota ; DNA ; Microbial Consortia ; }, abstract = {By deciphering information encoded in degraded ancient DNA extracted from up to million-years-old samples, molecular paleomicrobiology enables to objectively retrace the temporal evolution of microbial species and communities. Assembly of full-length genomes of ancient pathogen lineages allows not only to follow historical epidemics in space and time but also to identify the acquisition of genetic features that represent landmarks in the evolution of the host-microbe interaction. Analysis of microbial community DNA extracted from essentially human paleo-artefacts (paleofeces, dental calculi) evaluates the relative contribution of diet, lifestyle and geography on the taxonomic and functional diversity of these guilds in which have been identified species that may have gone extinct in today's human microbiome. As for non-host-associated environmental samples, such as stratified sediment cores, analysis of their DNA illustrates how and at which pace microbial communities are affected by local or widespread environmental disturbance. Description of pre-disturbance microbial diversity patterns can aid in evaluating the relevance and effectiveness of remediation policies. We finally discuss how recent achievements in paleomicrobiology could contribute to microbial biotechnology in the fields of medical microbiology and food science to trace the domestication of microorganisms used in food processing or to illustrate the historic evolution of food processing microbial consortia.}, }
@article {pmid38225565, year = {2024}, author = {Rojas-Velazquez, D and Kidwai, S and Kraneveld, AD and Tonda, A and Oberski, D and Garssen, J and Lopez-Rincon, A}, title = {Methodology for biomarker discovery with reproducibility in microbiome data using machine learning.}, journal = {BMC bioinformatics}, volume = {25}, number = {1}, pages = {26}, pmid = {38225565}, issn = {1471-2105}, mesh = {Humans ; RNA, Ribosomal, 16S/genetics ; *Autism Spectrum Disorder ; Reproducibility of Results ; *Diabetes Mellitus, Type 2/genetics ; *Biomedical Research ; Machine Learning ; Biomarkers ; *Microbiota/genetics ; }, abstract = {BACKGROUND: In recent years, human microbiome studies have received increasing attention as this field is considered a potential source for clinical applications. With the advancements in omics technologies and AI, research focused on the discovery for potential biomarkers in the human microbiome using machine learning tools has produced positive outcomes. Despite the promising results, several issues can still be found in these studies such as datasets with small number of samples, inconsistent results, lack of uniform processing and methodologies, and other additional factors lead to lack of reproducibility in biomedical research. In this work, we propose a methodology that combines the DADA2 pipeline for 16s rRNA sequences processing and the Recursive Ensemble Feature Selection (REFS) in multiple datasets to increase reproducibility and obtain robust and reliable results in biomedical research.<br><br>RESULTS: Three experiments were performed analyzing microbiome data from patients/cases in Inflammatory Bowel Disease (IBD), Autism Spectrum Disorder (ASD), and Type 2 Diabetes (T2D). In each experiment, we found a biomarker signature in one dataset and applied to 2 other as further validation. The effectiveness of the proposed methodology was compared with other feature selection methods such as K-Best with F-score and random selection as a base line. The Area Under the Curve (AUC) was employed as a measure of diagnostic accuracy and used as a metric for comparing the results of the proposed methodology with other feature selection methods. Additionally, we use the Matthews Correlation Coefficient (MCC) as a metric to evaluate the performance of the methodology as well as for comparison with other feature selection methods.<br><br>CONCLUSIONS: We developed a methodology for reproducible biomarker discovery for 16s rRNA microbiome sequence analysis, addressing the issues related with data dimensionality, inconsistent results and validation across independent datasets. The findings from the three experiments, across 9 different datasets, show that the proposed methodology achieved higher accuracy compared to other feature selection methods. This methodology is a first approach to increase reproducibility, to provide robust and reliable results.}, }
@article {pmid38224872, year = {2024}, author = {Kau, AL and Rosen, AL and Rosas-Salazar, C}, title = {Can Therapeutic Targeting of the Human Microbiome Influence Asthma Management? A Pro/Con Debate.}, journal = {The journal of allergy and clinical immunology. In practice}, volume = {12}, number = {4}, pages = {863-869}, doi = {10.1016/j.jaip.2023.12.053}, pmid = {38224872}, issn = {2213-2201}, mesh = {Humans ; *Microbiota ; *Asthma/therapy ; *Gastrointestinal Microbiome ; Respiratory System ; Inflammation ; }, abstract = {Asthma is a clinically heterogeneous disease, and despite substantial improvements in therapies, there remains an unmet need for well-tolerated, effective treatments. Observational studies have demonstrated that alterations in the respiratory and gut microbiome are associated with the development of asthma and its severity. These findings are supported by preclinical models demonstrating that respiratory and gut microbes can alter airway inflammation. Therapeutic approaches to target the human microbiome have been increasingly applied to a wide range of acute and chronic diseases, but there are currently no microbiome-based therapeutics approved for the treatment of asthma. This clinical commentary addresses the future role of microbiome-based therapeutics in asthma management from both a pro and con perspective. We examine (1) the prospects for clinical studies demonstrating a causal relationship between the human microbiome and the severity of asthma; (2) the challenges and potential solutions for designing, testing, and implementing a microbiome-based therapeutic; and (3) the possibility of microbiome-based therapeutics for conditions comorbid to asthma. We conclude by identifying research priorities that will help determine the future of microbiome-based therapeutics for the management of asthma.}, }
@article {pmid38222203, year = {2023}, author = {Torres, AR and Morris, S and Benson, M and Wilkinson, C and Lyon, R}, title = {Stimulation of Pro-inflammatory Cytokines in Mixed Cultures of Peripheral Blood Mononuclear Cells and Anaerobic Bacteria.}, journal = {Cureus}, volume = {15}, number = {12}, pages = {e50586}, pmid = {38222203}, issn = {2168-8184}, abstract = {In the last couple of decades, much progress has been made in studying bacteria living in humans. However, there is much more to learn about bacteria immune cell interactions. Here, we show that anaerobic bacteria do not grow when cultured overnight with human cells under atmospheric air. Air contains about 18% oxygen, which inhibits the growth of these bacteria while supporting the cultivation of human cells. The bacteria cultured with human peripheral blood mononuclear cells (PBMCs) inflamed with phytohemagglutinin (PHA) greatly increased the production of proinflammatory cytokines like tumor necrosis factor-alpha (TNFα) while inhibiting the production of monocyte chemoattractant protein-1 (MCP-1), an important chemokine.}, }
@article {pmid38219382, year = {2024}, author = {Whyte, M and Douwes, J and Ranta, A}, title = {Green space and stroke: A scoping review of the evidence.}, journal = {Journal of the neurological sciences}, volume = {457}, number = {}, pages = {122870}, doi = {10.1016/j.jns.2024.122870}, pmid = {38219382}, issn = {1878-5883}, mesh = {Humans ; Parks, Recreational ; Cross-Sectional Studies ; *Air Pollution ; *Stroke/epidemiology/therapy ; Exercise ; Environmental Exposure ; }, abstract = {BACKGROUND: Global industrialisation and urbanisation has led to an increased interest in the link between the environment and health. Stroke is a major cause of morbidity and mortality, and there is increased evidence that environmental factors may affect both the incidence and severity of stroke. This review summarises the evidence for relationship between green space exposure and stroke incidence and outcomes.<br><br>METHODS: We conducted a literature search in Medline and Scopus until 1 August 2023, and screened references of relevant articles. Selected articles were appraised for their relevance, and critically reviewed. The findings were thematically categorised.<br><br>RESULTS: Of the 1342 papers identified, 27 were included. These involved a mix of study designs (cohort, cross-sectional, quasi-experimental, time stratified case crossover and ecological). There was consistent evidence indicating a protective association between green space exposure and disability and stroke-related death with mortality hazard ratios between 0.66 and 0.95. Most studies also showed that green space was inversely associated with stroke risk, with risk estimates from studies showing a protective effect ranging between 0.4 and 0.98; however, results were more mixed and some did not reach statistical significance. The moderating effects of green spaces on ambient temperatures, noise and air pollution, and psychosocial health plus greater enjoyment and opportunity for exercise and enrichment of the human microbiome may underly these associations.<br><br>CONCLUSION: There is likely some protective effect of green space on stroke, with the benefits most convincingly shown for post-stroke outcomes. More research is recommended to confirm the protective association between green space exposure and reduced stroke risk.}, }
@article {pmid38215690, year = {2024}, author = {Zeng, W and Wu, J and Xie, H and Xu, H and Liang, D and He, Q and Yang, X and Liu, C and Gong, J and Zhang, Q and Luo, Z and Chen, Y and He, Z and Lan, P}, title = {Enteral nutrition promotes the remission of colitis by gut bacteria-mediated histidine biosynthesis.}, journal = {EBioMedicine}, volume = {100}, number = {}, pages = {104959}, pmid = {38215690}, issn = {2352-3964}, mesh = {Humans ; Animals ; Mice ; Enteral Nutrition ; Interleukin-10/genetics ; Histidine ; *Colitis/etiology/therapy ; *Crohn Disease/microbiology ; Bacteria/genetics ; Disease Models, Animal ; DNA, Ribosomal ; *Firmicutes ; }, abstract = {BACKGROUND: Exclusive enteral nutrition (EEN) is an important alternative strategy for patients with Crohn's disease (CD), and during this process, microbiota alterations have been observed. However, the underlying mechanisms by which EEN reduces intestinal inflammation are currently unclear.<br><br>METHODS: The therapeutic potential of enteral nutrition (EN) was assessed using various mouse models. Fecal full-length 16S rDNA sequencing analysis and several CD metagenome datasets were used to identify the candidate therapeutic bacteria Faecalibaculum rodentium (F.&#xa0;rodentium). Whole genome sequencing of F.&#xa0;rodentium and widely-targeted metabolome analysis of the supernatant showed that EN-induced F.&#xa0;rodentium accumulation protected against colitis via histidine biosynthesis.<br><br>FINDINGS: The therapeutic potential of EN therapy was observed in both dextran sulfate sodium (DSS)-induced colitis and Il10[-/-] spontaneous colitis mouse models. Accumulation of F.&#xa0;rodentium after EN therapy was determined using full-length 16S rDNA sequencing and verified with several metagenome datasets from patients with CD. Colonization of an isolated F.&#xa0;rodentium could reduce colitis in Il10[-/-] mice. Significant histidine enrichment was observed in the F.&#xa0;rodentium culture supernatant, and a series of histidine biosynthesis genes were observed in the F.&#xa0;rodentium genome. Engineered Escherichia coli Nissle 1917 (EcN), encoding the heterologous hisG of F.&#xa0;rodentium (EcN-hisG), which was a key driver of histidine biosynthesis in F.&#xa0;rodentium, was found to protect against colitis.<br><br>INTERPRETATION: This study suggests that EN-induced F.&#xa0;rodentium accumulation protects against colitis in mice via gut bacteria-mediated histidine biosynthesis.<br><br>FUNDING: A full list of funding bodies can be found in the Acknowledgements section.}, }
@article {pmid38215640, year = {2024}, author = {Li, J and Li, Y and Zhou, L and Li, C and Liu, J and Liu, D and Fu, Y and Wang, Y and Tang, J and Zhou, L and Tan, S and Wang, L}, title = {The human microbiome and benign prostatic hyperplasia: Current understandings and clinical implications.}, journal = {Microbiological research}, volume = {281}, number = {}, pages = {127596}, doi = {10.1016/j.micres.2023.127596}, pmid = {38215640}, issn = {1618-0623}, mesh = {Male ; Aged ; Middle Aged ; Humans ; *Prostatic Hyperplasia/etiology/metabolism ; Inflammation ; *Metabolic Syndrome/complications ; *Microbiota ; }, abstract = {The research of the human microbiome in the preceding decade has yielded novel perspectives on human health and diseases. Benign prostatic hyperplasia (BPH) is a common disease in middle-aged and elderly males, which negatively affects the life quality. Existing evidence has indicated that the human microbiome, including urinary, intra-prostate, gut, oral and blood microbiome may exert a significant impact on the natural progression of BPH. The dysbiosis of the microbiome may induce inflammation at either a local or systemic level, thereby affecting the BPH. Moreover, metabolic syndrome (MetS) caused by the microbiome can also be involved in the development of BPH. Additionally, alterations in the microbiome composition during the senility process may serve as another cause of the BPH. Here, we summarize the influence of human microbiome on BPH and explore how the microbiome is linked to BPH through inflammation, MetS, and senility. In addition, we propose promising areas of investigation and discuss the implications for advancing therapeutic approaches.}, }
@article {pmid38214604, year = {2024}, author = {Hartikainen, AK and Khan, I and Karjalainen, EK and Renkonen-Sinisalo, L and Arkkila, P and Jalanka, J and Lepistö, AH and Satokari, R}, title = {Microbiota and mucosal gene expression of fecal microbiota transplantation or placebo treated patients with chronic pouchitis.}, journal = {Gut microbes}, volume = {16}, number = {1}, pages = {2295445}, pmid = {38214604}, issn = {1949-0984}, mesh = {Humans ; Fecal Microbiota Transplantation/adverse effects ; *Pouchitis/therapy/metabolism ; *Colitis, Ulcerative/therapy ; *Gastrointestinal Microbiome ; *Microbiota ; Gene Expression ; Feces ; }, abstract = {Altered microbiota and impaired host immune function have been linked to the pathogenesis of pouchitis. We used 16S rRNA gene sequencing and RNA sequencing data from a previous randomized clinical trial (RCT) on fecal microbiota transplantation (FMT) therapy in 26 chronic pouchitis patients with one-year follow-up. We analyzed changes in both luminal and mucosal microbiota composition, as well as in host mucosal gene expression to gain insights into the host-microbiota interactions possibly underlying clinical outcomes of the patients. Antibiotic type and pattern of use were significant drivers of the luminal microbiota at baseline. Differential gene expression analysis indicated transition from ileal to colonic gene expression in the pouch, and upregulation in inflammation- and immune system-related pathways in the pouch. At 4 weeks, the non-relapsed FMT patients had a lower microbiota dissimilarity to the donor than the non-relapsed placebo patients (p = .02). While two FMT-treated patients showed a shift toward the donor's microbiota during the one-year follow-up, the overall FMT microbiota modulation effect was low. Patient's luminal and mucosal microbiota profiles were unstable in both FMT and placebo groups. Expression of the chemokine receptor CXCR4 was downregulated at 52 weeks compared to the baseline in the non-relapsed patients in both FMT and placebo groups. Microbiota modulation by FMT seems to be low in this patient group. The microbiota composition or alterations did not explain the relapse status of the patients. Some evidence for remission-related host gene expression pattern was found; specifically, CXCR4 expression may have a role in sustained remission.}, }
@article {pmid38212576, year = {2024}, author = {Osadchiy, V and Belarmino, A and Kianian, R and Sigalos, JT and Ancira, JS and Kanie, T and Mangum, SF and Tipton, CD and Hsieh, TM and Mills, JN and Eleswarapu, SV}, title = {Semen microbiota are dramatically altered in men with abnormal sperm parameters.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {1068}, pmid = {38212576}, issn = {2045-2322}, mesh = {Humans ; Male ; Cross-Sectional Studies ; Fertility ; *Infertility, Male ; *Lactobacillus ; *Semen ; Semen Analysis ; Sperm Count ; Sperm Motility ; Spermatozoa ; }, abstract = {There has recently been an explosion of studies implicating the human microbiome in playing a critical role in many disease and wellness states. The etiology of abnormal semen analysis (SA) parameters is not identified in 30% of cases; investigations involving the semen microbiome may bridge this gap. Here, we explore the relationship between the semen microbiome and alterations of sperm parameters. We recruited men presenting for fertility evaluation or vasectomy consultation with proven biological paternity. SA and next generation sequencing was performed. Differential abundance testing using Analysis of composition of Microbiota with Bias Correction (ANCOM-BC) was performed along with canonical correlational analysis for microbial community profiling. Men with abnormal (N = 27) sperm motility showed a higher abundance of Lactobacillus iners compared to those with normal (N = 46) sperm motility (mean proportion 9.4% versus 2.6%, p = 0.046). This relationship persisted on canonical correlational analysis (r = 0.392, p = 0.011). Men with abnormal sperm concentration (N = 20) showed a higher abundance of Pseudomonas stutzeri (2.1% versus 1.0%, p = 0.024) and Pseudomonas fluorescens (0.9% versus 0.7%, p = 0.010), but a lower abundance of Pseudomonas putida (0.5% versus 0.8%, p = 0.020), compared to those with normal sperm concentration (N = 53). Major limitations are related to study design (cross-sectional, observational). Our results suggest that a small group of microorganisms may play a critical role in observed perturbations of SA parameters. Some of these microbes, most notably Lactobacillus iners, have been described extensively within other, fertility-related, contexts, whereas for others, this is the first report where they have potentially been implicated. Advances in our understanding of the semen microbiome may contribute to potentially new therapeutic avenues for correcting impairments in sperm parameters and improving male fertility.}, }
@article {pmid38211733, year = {2024}, author = {Huang, X and Kantonen, J and Nowlan, K and Nguyen, NA and Jokiranta, ST and Kuivanen, S and Heikkilä, N and Mahzabin, S and Kantele, A and Vapalahti, O and Myllykangas, L and Heinonen, S and Mäyränpää, MI and Strandin, T and Kekäläinen, E}, title = {Mucosal-Associated Invariant T Cells are not susceptible in vitro to SARS-CoV-2 infection but accumulate into the lungs of COVID-19 patients.}, journal = {Virus research}, volume = {341}, number = {}, pages = {199315}, pmid = {38211733}, issn = {1872-7492}, mesh = {Humans ; *Mucosal-Associated Invariant T Cells ; *COVID-19 ; Angiotensin-Converting Enzyme 2 ; Leukocytes, Mononuclear ; SARS-CoV-2 ; Lung ; *Lymphopenia ; }, abstract = {Prolonged T cell lymphopenia is common in COVID-19, caused by SARS-CoV-2. While the mechanisms of lymphopenia during COVID-19 remain elusive, it is especially pronounced in a specialized innate-like T cell population called Mucosal Associated Invariant T cells (MAITs). MAITs has been suggested to express Angiotensin-Converting Enzyme 2 (ACE2), which is the well-known cellular receptor for SARS-CoV-2. However, it is still unclear if SARS-CoV-2 can infect or affect MAIT cells directly. In this study, we performed multicolor flow cytometry on peripheral blood mononuclear cells obtained from COVID-19 patients to assess the frequencies of CD8[+]Vα7.2[+]CD161[+] MAIT subsets at acute and convalescent disease phases. The susceptibility of MAITs and T cells to direct exposure by SARS-CoV-2 was analysed using cells isolated from healthy donor buffy coats by viability assays, virus-specific RT-PCR, and flow cytometry. In situ lung immunofluorescence was used to evaluate retention of T cells, especially MAIT cells, in lung tissues during acute COVID-19. Our study confirms previous reports indicating that circulating MAITs are activated, and their frequency is declined in patients with acute SARS-CoV-2 infection, whereas an accumulation of MAITs and T cells was seen in the lung tissue of individuals with fatal COVID-19. However, despite a fraction of MAITs found to express ACE2, no evidence for the susceptibility of MAITs for direct infection or activation by SARS-CoV-2 particles was observed. Thus, their activation and decline in the circulation is most likely explained by indirect mechanisms involving other immune cells and cytokine-induced pro-inflammatory environment but not by direct exposure to viral particles at the infection site.}, }
@article {pmid38211629, year = {2024}, author = {Pan, D and Chung, S and Nielsen, E and Niederman, MS}, title = {Aspiration Pneumonia.}, journal = {Seminars in respiratory and critical care medicine}, volume = {45}, number = {2}, pages = {237-245}, doi = {10.1055/s-0043-1777772}, pmid = {38211629}, issn = {1098-9048}, mesh = {Humans ; Aged ; *Pneumonia, Aspiration/etiology/prevention &amp; control ; *Pneumonia/complications ; *Deglutition Disorders/therapy/complications ; Risk Factors ; *Respiratory Tract Infections/complications ; }, abstract = {Aspiration pneumonia is a lower respiratory tract infection that results from inhalation of foreign material, often gastric and oropharyngeal contents. It is important to distinguish this from a similar entity, aspiration with chemical pneumonitis, as treatment approaches may differ. An evolving understanding of the human microbiome has shed light on the pathogenesis of aspiration pneumonia, suggesting that dysbiosis, repetitive injury, and inflammatory responses play a role in its development. Risk factors for aspiration events involve a complex interplay of anatomical and physiological dysfunctions in the nervous, gastrointestinal, and pulmonary systems. Current treatment strategies have shifted away from anaerobic organisms as leading pathogens. Prevention of aspiration pneumonia primarily involves addressing oropharyngeal dysphagia, a significant risk factor for aspiration pneumonia, particularly among elderly individuals and those with cognitive and neurodegenerative disorders.}, }
@article {pmid38206940, year = {2024}, author = {Rogers, MB and Harner, A and Buhay, M and Firek, B and Methé, B and Morris, A and Palmer, OMP and Promes, SB and Sherwin, RL and Southerland, L and Vieira, AR and Yende, S and Morowitz, MJ and Huang, DT}, title = {The salivary microbiota of patients with acute lower respiratory tract infection-A multicenter cohort study.}, journal = {PloS one}, volume = {19}, number = {1}, pages = {e0290062}, pmid = {38206940}, issn = {1932-6203}, mesh = {Adult ; Humans ; Prospective Studies ; *Microbiota ; *Respiratory Tract Infections/microbiology ; *Gastrointestinal Microbiome ; Feces/microbiology ; RNA, Ribosomal, 16S/genetics ; }, abstract = {The human microbiome contributes to health and disease, but the oral microbiota is understudied relative to the gut microbiota. The salivary microbiota is easily accessible, underexplored, and may provide insight into response to infections. We sought to determine the composition, association with clinical features, and heterogeneity of the salivary microbiota in patients with acute lower respiratory tract infection (LRTI). We conducted a multicenter prospective cohort study of 147 adults with acute LRTI presenting to the emergency department of seven hospitals in three states (Pennsylvania, Michigan, and Ohio) between May 2017 and November 2018. Salivary samples were collected in the emergency department, at days 2-5 if hospitalized, and at day 30, as well as fecal samples if patients were willing. We compared salivary microbiota profiles from patients to those of healthy adult volunteers by sequencing and analyzing bacterial 16-rRNA. Compared to healthy volunteers, the salivary microbiota of patients with LRTI was highly distinct and strongly enriched with intestinal anaerobes such as Bacteroidaceae, Ruminococcaceae, and Lachnospiraceae (e.g., mean 10% relative abundance of Bacteroides vs < 1% in healthy volunteers). Within the LRTI population, COPD exacerbation was associated with altered salivary microbiota composition compared to other LRTI conditions. The largest determinant of microbiota variation within the LRTI population was geography (city in which the hospital was located).}, }
@article {pmid38205958, year = {2024}, author = {Örmälä-Tiznado, A-M and Allander, L and Maatallah, M and Kabir, MH and Brisse, S and Sandegren, L and Patpatia, S and Coorens, M and Giske, CG}, title = {Molecular characteristics, fitness, and virulence of high-risk and non-high-risk clones of carbapenemase-producing Klebsiella pneumoniae.}, journal = {Microbiology spectrum}, volume = {12}, number = {2}, pages = {e0403622}, pmid = {38205958}, issn = {2165-0497}, support = {2016-02889//Vetenskapsr&#xe5;det (VR)/ ; }, mesh = {Animals ; Virulence/genetics ; *Klebsiella pneumoniae/genetics ; *Klebsiella Infections/microbiology ; Bacterial Proteins/genetics ; beta-Lactamases/genetics ; Virulence Factors/genetics ; Larva ; Clone Cells ; Anti-Bacterial Agents/therapeutic use ; Microbial Sensitivity Tests ; }, abstract = {Extensively drug-resistant (XDR) Klebsiella pneumoniae inflict a notable burden on healthcare worldwide. Of specific concern are strains producing carbapenem-hydrolyzing enzymes, as the therapeutic options for these strains are still very limited. Specific sequence types of K. pneumoniae have been noted for their epidemic occurrence globally, but the mechanisms behind the success of specific clones remain unclear. Herein, we have characterized 20 high-risk clones (HiRCs) and 10 non-HiRCs of XDR K. pneumoniae, exploring factors connected to the epidemiological success of some clones. Isolates were subjected to core genome multilocus sequence typing analysis to determine the clonal relationships of the isolates and subsequently characterized with regard to features known to be linked to overall bacterial fitness and virulence. The genomes were analyzed in silico for capsule types, O antigens, virulence factors, antimicrobial resistance genes, prophages, and CRISPR-Cas loci. In vitro growth experiments were conducted to retrieve proxies for absolute and relative fitness for 11 HiRC and 9 non-HiRC isolates selected based on the clonal groups they belonged to, and infections in a Galleria mellonella insect model were used to evaluate the virulence of the isolates in vivo. This study did not find evidence that virulence factors, prophages, CRISPR-Cas loci, or fitness measured in vitro alone would contribute to the global epidemiological success of specific clones of carbapenemase-producing XDR K. pneumoniae. However, this study did find the HiRC group to be more virulent than the non-HiRC group when measured in vivo in a model with G. mellonella. This suggests that the virulence and epidemiological success of certain clones of K. pneumoniae cannot be explained by individual traits investigated in this study and thus warrant further experiments in the future.IMPORTANCEHerein, we explored potential explanations for the successfulness of some epidemic or high-risk clones of carbapenemase-producing Klebsiella pneumoniae. We found differences in mortality in a larva model but found no clear genomic differences in known virulence markers. Most of the research on virulence in K. pneumoniae has been focused on hypervirulent strains, but here, we try to understand differences within the group of highly resistant strains. The results from the larva virulence model could be used to design experiments in higher animals. Moreover, the data could provide further support to a differentiated infection control approach against extensively drug-resistant strains, based on their classification as high-risk clones.}, }
@article {pmid38205031, year = {2024}, author = {Troci, A and Philippen, S and Rausch, P and Rave, J and Weyland, G and Niemann, K and Jessen, K and Schmill, LP and Aludin, S and Franke, A and Berg, D and Bang, C and Bartsch, T}, title = {Disease- and stage-specific alterations of the oral and fecal microbiota in Alzheimer's disease.}, journal = {PNAS nexus}, volume = {3}, number = {1}, pages = {pgad427}, pmid = {38205031}, issn = {2752-6542}, abstract = {Microbial communities in the intestinal tract are suggested to impact the ethiopathogenesis of Alzheimer's disease (AD). The human microbiome might modulate neuroinflammatory processes and contribute to neurodegeneration in AD. However, the microbial compositions in patients with AD at different stages of the disease are still not fully characterized. We used 16S rRNA analyses to investigate the oral and fecal microbiota in patients with AD and mild cognitive impairment (MCI; n = 84), at-risk individuals (APOE4 carriers; n = 17), and healthy controls (n = 50) and investigated the relationship of microbial communities and disease-specific markers via multivariate- and network-based approaches. We found a slightly decreased diversity in the fecal microbiota of patients with AD (average Chao1 diversity for AD = 212 [SD = 66]; for controls = 215 [SD = 55]) and identified differences in bacterial abundances including Bacteroidetes, Ruminococcus, Sutterella, and Porphyromonadaceae. The diversity in the oral microbiota was increased in patients with AD and at-risk individuals (average Chao1 diversity for AD = 174 [SD = 60], for at-risk group = 195 [SD = 49]). Gram-negative proinflammatory bacteria including Haemophilus, Neisseria, Actinobacillus, and Porphyromonas were dominant oral bacteria in patients with AD and MCI and the abundance correlated with the cerebrospinal fluid biomarker. Taken together, we observed a strong shift in the fecal and the oral communities of patients with AD already prominent in prodromal and, in case of the oral microbiota, in at-risk stages. This indicates stage-dependent alterations in oral and fecal microbiota in AD which may contribute to the pathogenesis via a facilitated intestinal and systemic inflammation leading to neuroinflammation and neurodegeneration.}, }
@article {pmid38204788, year = {2024}, author = {Rintarhat, P and Cho, YJ and Koh, H and Park, S and Lee, EJ and Lim, H and Noh, J and Lee, DW and Jung, WH}, title = {Assessment of DNA extraction methods for human gut mycobiome analysis.}, journal = {Royal Society open science}, volume = {11}, number = {1}, pages = {231129}, pmid = {38204788}, issn = {2054-5703}, abstract = {The gut mycobiome plays an important role in the health and disease of the human gut, but its exact function is still under investigation. While there is a wealth of information available on the bacterial community of the human gut microbiome, research on the fungal community is still relatively limited. In particular, technical methodologies for mycobiome analysis, especially the DNA extraction method for human faecal samples, varied in different studies. In the current study, two commercial kits commonly used in DNA extraction, the QIAamp® Fast DNA Stool Mini Kit and DNeasy PowerSoil Pro Kit, and one manual method, the International Human Microbiome Standards Protocol Q, were compared. Furthermore, the effectiveness of two different bead-beating machines, the Mini-Beadbeater-16 and FastPrep-24[TM] 5G, was compared in parallel. A mock fungal community with a known composition of fungal strains was also generated and included to compare different DNA extraction methods. Our results suggested that the method using the DNeasy PowerSoil Pro Kit and Mini-Beadbeater-16 provides the best results to extract DNA from human faecal samples. Based on our data, we propose a standard operating procedure for DNA extraction from human faecal samples for mycobiome analysis.}, }
@article {pmid38204360, year = {2024}, author = {Kiran, A and Hanachi, M and Alsayed, N and Fassatoui, M and Oduaran, OH and Allali, I and Maslamoney, S and Meintjes, A and Zass, L and Rocha, JD and Kefi, R and Benkahla, A and Ghedira, K and Panji, S and Mulder, N and Fadlelmola, FM and Souiai, O}, title = {The African Human Microbiome Portal: a public web portal of curated metagenomic metadata.}, journal = {Database : the journal of biological databases and curation}, volume = {2024}, number = {}, pages = {}, pmid = {38204360}, issn = {1758-0463}, support = {U24 HG006941/HG/NHGRI NIH HHS/United States ; }, mesh = {Humans ; *Metadata ; Metagenome ; Databases, Factual ; Metagenomics ; *Microbiota/genetics ; }, abstract = {There is growing evidence that comprehensive and harmonized metadata are fundamental for effective public data reusability. However, it is often challenging to extract accurate metadata from public repositories. Of particular concern is the metagenomic data related to African individuals, which often omit important information about the particular features of these populations. As part of a collaborative consortium, H3ABioNet, we created a web portal, namely the African Human Microbiome Portal (AHMP), exclusively dedicated to metadata related to African human microbiome samples. Metadata were collected from various public repositories prior to cleaning, curation and harmonization according to a pre-established guideline and using ontology terms. These metadata sets can be accessed at https://microbiome.h3abionet.org/. This web portal is open access and offers an interactive visualization of 14 889 records from 70 bioprojects associated with 72 peer reviewed research articles. It also offers the ability to download harmonized metadata according to the user's applied filters. The AHMP thereby supports metadata search and retrieve operations, facilitating, thus, access to relevant studies linked to the African Human microbiome. Database URL: https://microbiome.h3abionet.org/.}, }
@article {pmid38201850, year = {2023}, author = {Toivio, L and Launonen, H and Lindén, J and Lehto, M and Vapaatalo, H and Salmenkari, H and Korpela, R}, title = {Ketogenic Diet High in Saturated Fat Promotes Colonic Claudin Expression without Changes in Intestinal Permeability to Iohexol in Healthy Mice.}, journal = {Nutrients}, volume = {16}, number = {1}, pages = {}, pmid = {38201850}, issn = {2072-6643}, support = {N/A//Finnish Concordia Fund/ ; N/A//Finnish Cultural Foundation/ ; N/A//Mary and Georg C. Ehrnrooth's Foundation/ ; N/A//Finska L&#xe4;kares&#xe4;llskapet/ ; N/A//Paulo Foundation/ ; N/A//Maud Kuistila Memorial Foundation/ ; #NNFOC0013659//Novo Nordisk (Finland)/ ; N/A//Wilhelm and Else Stockmann Foundation/ ; }, mesh = {Male ; Animals ; Mice ; Mice, Inbred C57BL ; *Diet, Ketogenic ; Claudins/genetics ; Iohexol ; Intestinal Barrier Function ; Interleukin-6/genetics ; Linoleic Acid ; Tight Junction Proteins/genetics ; Alkaline Phosphatase ; }, abstract = {Ketogenic diets (KDs) have been studied in preclinical models of intestinal diseases. However, little is known of how the fat source of these diets influences the intestinal barrier. Herein, we studied the impact of four-week feeding with KD high either in saturated fatty acids (SFA-KD) or polyunsaturated linoleic acid (LA-KD) on paracellular permeability of the intestine to iohexol in healthy male C57BL/6J mice. We investigated jejunal and colonic tight junction protein expression, histological changes, and inflammatory markers (Il1b, Il6, Tnf, and Lcn2), as well as the activity and expression of intestinal alkaline phosphatase (IAP) in feces and jejunal tissue, respectively, and plasma lipopolysaccharide. KDs did not change intestinal permeability to iohexol after two or twenty-six days of feeding regardless of fat quality. SFA-KD, but not LA-KD, upregulated the colonic expression of tight junction proteins claudin-1 and -4, as well as the activity of IAP. Both KDs resulted in increased epithelial vacuolation in jejunum, and this was pronounced in SFA-KD. Jejunal Il1β expression was lower and colonic Il6 expression higher in LA-KD compared to SFA-KD. In colon, Tnf mRNA was increased in LA-KD when compared to controls. Overall, the results suggest that KDs do not influence intestinal permeability to iohexol but elicit changes in colonic tight junction proteins and inflammatory markers in both jejunum and colon. Future research will show whether these changes become of importance upon proinflammatory insults.}, }
@article {pmid38201695, year = {2023}, author = {Savitskaya, I and Zhantlessova, S and Kistaubayeva, A and Ignatova, L and Shokatayeva, D and Sinyavskiy, Y and Kushugulova, A and Digel, I}, title = {Prebiotic Cellulose-Pullulan Matrix as a "Vehicle" for Probiotic Biofilm Delivery to the Host Large Intestine.}, journal = {Polymers}, volume = {16}, number = {1}, pages = {}, pmid = {38201695}, issn = {2073-4360}, support = {AP09259491//the Ministry of Science and Higher Education of the Republic of Kazakhstan/ ; }, abstract = {This study describes the development of a new combined polysaccharide-matrix-based technology for the immobilization of Lactobacillus rhamnosus GG (LGG) bacteria in biofilm form. The new composition allows for delivering the bacteria to the digestive tract in a manner that improves their robustness compared with planktonic cells and released biofilm cells. Granules consisting of a polysaccharide matrix with probiotic biofilms (PMPB) with high cell density (>9 log CFU/g) were obtained by immobilization in the optimized nutrient medium. Successful probiotic loading was confirmed by fluorescence microscopy and scanning electron microscopy. The developed prebiotic polysaccharide matrix significantly enhanced LGG viability under acidic (pH 2.0) and bile salt (0.3%) stress conditions. Enzymatic extract of feces, mimicking colon fluid in terms of cellulase activity, was used to evaluate the intestinal release of probiotics. PMPB granules showed the ability to gradually release a large number of viable LGG cells in the model colon fluid. In vivo, the oral administration of PMPB granules in rats resulted in the successful release of probiotics in the colon environment. The biofilm-forming incubation method of immobilization on a complex polysaccharide matrix tested in this study has shown high efficacy and promising potential for the development of innovative biotechnologies.}, }
@article {pmid38200571, year = {2024}, author = {Xu, H and Wang, T and Miao, Y and Qian, M and Yang, Y and Wang, S}, title = {MK-BMC: a Multi-Kernel framework with Boosted distance metrics for Microbiome data for Classification.}, journal = {Bioinformatics (Oxford, England)}, volume = {40}, number = {1}, pages = {}, pmid = {38200571}, issn = {1367-4811}, support = {//Department of Biostatistics, Columbia University/ ; }, mesh = {Humans ; *Microbiota ; *Gastrointestinal Microbiome ; Phylogeny ; }, abstract = {MOTIVATION: Research on human microbiome has suggested associations with human health, opening opportunities to predict health outcomes using microbiome. Studies have also suggested that diverse forms of taxa such as rare taxa that are evolutionally related and abundant taxa that are evolutionally unrelated could be associated with or predictive of a health outcome. Although prediction models were developed for microbiome data, no prediction models currently exist that use multiple forms of microbiome-outcome associations.<br><br>RESULTS: We developed MK-BMC, a Multi-Kernel framework with Boosted distance Metrics for Classification using microbiome data. We propose to first boost widely used distance metrics for microbiome data using taxon-level association signal strengths to up-weight taxa that are potentially associated with an outcome of interest. We then propose a multi-kernel prediction model with one kernel capturing one form of association between taxa and the outcome, where a kernel measures similarities of microbiome compositions between pairs of samples being transformed from a proposed boosted distance metric. We demonstrated superior prediction performance of (i) boosted distance metrics for microbiome data over original ones and (ii) MK-BMC over competing methods through extensive simulations. We applied MK-BMC to predict thyroid, obesity, and inflammatory bowel disease status using gut microbiome data from the American Gut Project and observed much-improved prediction performance over that of competing methods. The learned kernel weights help us understand contributions of individual microbiome signal forms nicely.<br><br>Source code together with a sample input dataset is available at https://github.com/HXu06/MK-BMC.}, }
@article {pmid38198280, year = {2024}, author = {Zhao, Z and Wang, J and Yu, H and Wang, X}, title = {Guide for phenotype-specific profiling of DNA G-quadruplex-regulated genes.}, journal = {STAR protocols}, volume = {5}, number = {1}, pages = {102820}, pmid = {38198280}, issn = {2666-1667}, mesh = {*DNA/genetics ; *G-Quadruplexes ; Phenotype ; }, abstract = {DNA G-quadruplex (G4) is a non-canonical four-stranded secondary structure that has been shown to play a role in epigenetic modulation of gene expression. Here, we present a primer on phenotype-specific profiling of DNA G-quadruplex-regulated genes. We provide guidance on in silico exploration of G4-related genes and phenotypes, and in vitro and in vivo validation of the relationship between G4 and phenotype. We describe commonly utilized techniques and detail critical steps involved in determining the phenotype-specific G4-regulated genes for subsequent investigations.}, }
@article {pmid38195358, year = {2024}, author = {Andary, CM and Al, KF and Chmiel, JA and Gibbons, S and Daisley, BA and Parvathy, SN and Maleki Vareki, S and Bowdish, DME and Silverman, MS and Burton, JP}, title = {Dissecting mechanisms of fecal microbiota transplantation efficacy in disease.}, journal = {Trends in molecular medicine}, volume = {30}, number = {3}, pages = {209-222}, doi = {10.1016/j.molmed.2023.12.005}, pmid = {38195358}, issn = {1471-499X}, mesh = {Humans ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; *Clostridioides difficile ; *Microbiota ; *Clostridium Infections/therapy ; Treatment Outcome ; }, abstract = {Fecal microbiota transplantation (FMT) has emerged as an alternative or adjunct experimental therapy for microbiome-associated diseases following its success in the treatment of recurrent Clostridioides difficile infections (rCDIs). However, the mechanisms of action involved remain relatively unknown. The term 'dysbiosis' has been used to describe microbial imbalances in relation to disease, but this traditional definition fails to consider the complex cross-feeding networks that define the stability of the microbiome. Emerging research transitions toward the targeted restoration of microbial functional networks in treating different diseases. In this review, we explore potential mechanisms responsible for the efficacy of FMT and future therapeutic applications, while revisiting definitions of 'dysbiosis' in favor of functional network restoration in rCDI, inflammatory bowel diseases (IBDs), metabolic diseases, and cancer.}, }
@article {pmid38194793, year = {2024}, author = {Kompoura, V and Karapantzou, I and Mitropoulou, G and Parisis, NA and Gkalpinos, VK and Anagnostou, VA and Tsiailanis, AD and Vasdekis, EP and Koutsaliaris, IK and Tsouka, AN and Karapetsi, L and Madesis, P and Letsiou, S and Florou, D and Koukkou, AI and Barbouti, A and Tselepis, AD and Kourkoutas, Y and Tzakos, AG}, title = {Exploiting the beneficial effects of Salvia officinalis L. extracts in human health and assessing their activity as potent functional regulators of food microbiota.}, journal = {Food chemistry}, volume = {441}, number = {}, pages = {138175}, doi = {10.1016/j.foodchem.2023.138175}, pmid = {38194793}, issn = {1873-7072}, mesh = {Humans ; *Salvia officinalis/chemistry ; Hydrogen Peroxide ; Plant Extracts/chemistry ; Phytochemicals/analysis ; Antioxidants/chemistry ; }, abstract = {Salvia officinalis L. has attracted scientific and industrial interest due to its pharmacological properties. However, its detailed phytochemical profile and its correlation with beneficial effects in the human microbiome and oxidative stress remained elusive. To unveil this, S. officinalis was collected from the region of Epirus and its molecular identity was verified with DNA barcoding. Phytochemical profile for both aqueous and ethanol-based extracts was determined by high-pressure liquid chromatography-tandem mass spectrometry and 103 phytochemicals were determined. The effect of S. officinalis extracts as functional regulators of food microbiota by stimulating the growth of Lacticaseibacillus rhamnosus strains and by suppressing evolution of pathogenic bacteria was verified. Furthermore, we recorded that both extracts exhibited a significant cellular protection against H2O2-induced DNA damage. Finally, both extracts exhibited strong inhibitory effect towards LDL oxidation. This study provides a comprehensive characterization of S. officinalis on its phytochemical components as also its potential impact in human microbiome and oxidative stress.}, }
@article {pmid38192800, year = {2024}, author = {Zhang, W and Tang, R and Yin, Y and Chen, J and Yao, L and Liu, B}, title = {Microbiome signatures in ischemic stroke: A systematic review.}, journal = {Heliyon}, volume = {10}, number = {1}, pages = {e23743}, pmid = {38192800}, issn = {2405-8440}, abstract = {Microbial structural changes and dysfunction play an important role in the development of cerebral ischemia. We searched PubMed, Embase, Web of Science, and Cochrane Library and conducted a systematic review to assess the relationship between the human microbiome and ischemic stroke. A total of 24 studies were included, and the intestinal bacterial communities detected in both stroke and healthy people were dominated by 4 main phyla, including Firmicutes, Bacteroidetes, Proteobacteria, and Actinobacteria. Significant diversity (alpha and beta) in patients with ischemic versus nonischemic stroke was observed in nine out of 18 studies, and 3 studies showed that the severity of ischemic stroke affected microbial diversity. The imbalance of bacteria that produce short-chain fatty acids (SCFAs) changes the bacterial metabolic pathway, and disorders in the level of bacterial metabolites (trimethylamine N-oxide TMAO) lead to significant changes in intestinal flora function, which may aggravate the severity of stroke and affect its prognosis. Further studies are needed to explore the relationship between the microbiome and ischemic stroke.}, }
@article {pmid38192296, year = {2023}, author = {Vernocchi, P and Marangelo, C and Guerrera, S and Del Chierico, F and Guarrasi, V and Gardini, S and Conte, F and Paci, P and Ianiro, G and Gasbarrini, A and Vicari, S and Putignani, L}, title = {Gut microbiota functional profiling in autism spectrum disorders: bacterial VOCs and related metabolic pathways acting as disease biomarkers and predictors.}, journal = {Frontiers in microbiology}, volume = {14}, number = {}, pages = {1287350}, pmid = {38192296}, issn = {1664-302X}, abstract = {BACKGROUND: Autism spectrum disorder (ASD) is a multifactorial neurodevelopmental disorder. Major interplays between the gastrointestinal (GI) tract and the central nervous system (CNS) seem to be driven by gut microbiota (GM). Herein, we provide a GM functional characterization, based on GM metabolomics, mapping of bacterial biochemical pathways, and anamnestic, clinical, and nutritional patient metadata.<br><br>METHODS: Fecal samples collected from children with ASD and neurotypical children were analyzed by gas-chromatography mass spectrometry coupled with solid phase microextraction (GC-MS/SPME) to determine volatile organic compounds (VOCs) associated with the metataxonomic approach by 16S rRNA gene sequencing. Multivariate and univariate statistical analyses assessed differential VOC profiles and relationships with ASD anamnestic and clinical features for biomarker discovery. Multiple web-based and machine learning (ML) models identified metabolic predictors of disease and network analyses correlated GM ecological and metabolic patterns.<br><br>RESULTS: The GM core volatilome for all ASD patients was characterized by a high concentration of 1-pentanol, 1-butanol, phenyl ethyl alcohol; benzeneacetaldehyde, octadecanal, tetradecanal; methyl isobutyl ketone, 2-hexanone, acetone; acetic, propanoic, 3-methyl-butanoic and 2-methyl-propanoic acids; indole and skatole; and o-cymene. Patients were stratified based on age, GI symptoms, and ASD severity symptoms. Disease risk prediction allowed us to associate butanoic acid with subjects older than 5 years, indole with the absence of GI symptoms and low disease severity, propanoic acid with the ASD risk group, and p-cymene with ASD symptoms, all based on the predictive CBCL-EXT scale. The HistGradientBoostingClassifier model classified ASD patients vs. CTRLs by an accuracy of 89%, based on methyl isobutyl ketone, benzeneacetaldehyde, phenyl ethyl alcohol, ethanol, butanoic acid, octadecane, acetic acid, skatole, and tetradecanal features. LogisticRegression models corroborated methyl isobutyl ketone, benzeneacetaldehyde, phenyl ethyl alcohol, skatole, and acetic acid as ASD predictors.<br><br>CONCLUSION: Our results will aid the development of advanced clinical decision support systems (CDSSs), assisted by ML models, for advanced ASD-personalized medicine, based on omics data integrated into electronic health/medical records. Furthermore, new ASD screening strategies based on GM-related predictors could be used to improve ASD risk assessment by uncovering novel ASD onset and risk predictors.}, }
@article {pmid38188629, year = {2023}, author = {Marzano, V and Mortera, SL and Marangelo, C and Piazzesi, A and Rapisarda, F and Pane, S and Del Chierico, F and Vernocchi, P and Romani, L and Campana, A and Palma, P and Putignani, L and , }, title = {The metaproteome of the gut microbiota in pediatric patients affected by COVID-19.}, journal = {Frontiers in cellular and infection microbiology}, volume = {13}, number = {}, pages = {1327889}, pmid = {38188629}, issn = {2235-2988}, mesh = {Adult ; Humans ; Child ; *Gastrointestinal Microbiome ; *COVID-19 ; *Microbiota ; Adjuvants, Immunologic ; Algorithms ; }, abstract = {INTRODUCTION: The gut microbiota (GM) play a significant role in the infectivity and severity of COVID-19 infection. However, the available literature primarily focuses on adult patients and it is known that the microbiota undergoes changes throughout the lifespan, with significant alterations occurring during infancy and subsequently stabilizing during adulthood. Moreover, children have exhibited milder symptoms of COVID-19 disease, which has been associated with the abundance of certain protective bacteria. Here, we examine the metaproteome of pediatric patients to uncover the biological mechanisms that underlie this protective effect of the GM.<br><br>METHODS: We performed nanoliquid chromatography coupled with tandem mass spectrometry on a high resolution analytical platform, resulting in label free quantification of bacterial protein groups (PGs), along with functional annotations via COG and KEGG databases by MetaLab-MAG. Additionally, taxonomic assignment was possible through the use of the lowest common ancestor algorithm provided by Unipept software.<br><br>RESULTS: A COVID-19 GM functional dissimilarity respect to healthy subjects was identified by univariate analysis. The alteration in COVID-19 GM function is primarily based on bacterial pathways that predominantly involve metabolic processes, such as those related to tryptophan, butanoate, fatty acid, and bile acid biosynthesis, as well as antibiotic resistance and virulence.<br><br>DISCUSSION: These findings highlight the mechanisms by which the pediatric GM could contribute to protection against the more severe manifestations of the disease in children. Uncovering these mechanisms can, therefore, have important implications in the discovery of novel adjuvant therapies for severe COVID-19.}, }
@article {pmid38187050, year = {2023}, author = {Feng, K and Ren, F and Xing, Z and Zhao, Y and Yang, C and Liu, J and Shang, Q and Wang, X and Wang, X}, title = {Microbiome and its implications in oncogenesis: a Mendelian randomization perspective.}, journal = {American journal of cancer research}, volume = {13}, number = {12}, pages = {5785-5804}, pmid = {38187050}, issn = {2156-6976}, abstract = {The human microbiome, an intricate ecological network, has garnered significant attention due to its potential implications in oncogenesis. This paper delves into the multifaceted relationships between the microbiome, its metabolites, and cancer development, emphasizing the human intestinal tract as the primary microbial habitat. Highlighting the potential causative associations between microbial disturbances and cancer progression, we underscore the role of specific bacterial strains in various cancers, such as stomach and colorectal cancer. Traditional causality assessment methods, like randomized controlled trials (RCTs), have limitations. Therefore, we advocate using Mendelian Randomization (MR) as a powerful alternative to study causal relationships, leveraging genetic variants as instrumental variables. With the proliferation of genome-wide association studies, MR harnesses genetic variations to infer causality, which is especially beneficial when addressing confounders like diet and lifestyle that can skew microbial research. We systematically review MR's application in understanding the microbiome-cancer nexus, emphasizing its strengths and challenges. While MR offers a unique perspective on causality, it faces hurdles like horizontal pleiotropy and weak instrumental variable bias. Integrating MR with multi-omics data, encompassing genomics, transcriptomics, proteomics, and metabolomics, holds promise for future research, potentially heralding groundbreaking discoveries in microbiology and genetics. This comprehensive review underscores the critical role of the human microbiome in oncogenesis and champions MR as an indispensable tool for advancing our understanding in this domain.}, }
@article {pmid38182316, year = {2024}, author = {Mir, TUG and Manhas, S and Khurshid Wani, A and Akhtar, N and Shukla, S and Prakash, A}, title = {Alterations in microbiome of COVID-19 patients and its impact on forensic investigations.}, journal = {Science &amp; justice : journal of the Forensic Science Society}, volume = {64}, number = {1}, pages = {81-94}, doi = {10.1016/j.scijus.2023.12.002}, pmid = {38182316}, issn = {1876-4452}, mesh = {Female ; Humans ; *COVID-19 ; *Microbiota ; Forensic Sciences ; Skin ; }, abstract = {The human microbiome is vital for maintaining human health and has garnered substantial attention in recent years, particularly in the context of the coronavirus disease 2019 (COVID-19) outbreak. Studies have underscored significant alterations in the microbiome of COVID-19 patients across various body niches, including the gut, respiratory tract, oral cavity, skin, and vagina. These changes manifest as shifts in microbiota composition, characterized by an increase in opportunistic pathogens and a decrease in beneficial commensal bacteria. Such microbiome transformations may play a pivotal role in influencing the course and severity of COVID-19, potentially contributing to the inflammatory response. This ongoing relationship between COVID-19 and the human microbiome serves as a compelling subject of research, underscoring the necessity for further investigations into the underlying mechanisms and their implications for patient health. Additionally, these alterations in the microbiome may have significant ramifications for forensic investigations, given the microbiome's potential in establishing individual characteristics. Consequently, changes in the microbiome could introduce a level of complexity into forensic determinations. As research progresses, a more profound understanding of the human microbiome within the context of COVID-19 may offer valuable insights into disease prevention, treatment strategies, and its potential applications in forensic science. Consequently, this paper aims to provide an overarching review of microbiome alterations due to COVID-19 and the associated impact on forensic applications, bridging the gap between the altered microbiome of COVID-19 patients and the challenges forensic investigations may encounter when analyzing this microbiome as a forensic biomarker.}, }
@article {pmid38181740, year = {2024}, author = {Sarkar, A and McInroy, CJA and Harty, S and Raulo, A and Ibata, NGO and Valles-Colomer, M and Johnson, KV and Brito, IL and Henrich, J and Archie, EA and Barreiro, LB and Gazzaniga, FS and Finlay, BB and Koonin, EV and Carmody, RN and Moeller, AH}, title = {Microbial transmission in the social microbiome and host health and disease.}, journal = {Cell}, volume = {187}, number = {1}, pages = {17-43}, pmid = {38181740}, issn = {1097-4172}, support = {P30 DK042086/DK/NIDDK NIH HHS/United States ; R35 GM138284/GM/NIGMS NIH HHS/United States ; K22 CA258960/CA/NCI NIH HHS/United States ; R01 GM134376/GM/NIGMS NIH HHS/United States ; R01 AG071684/AG/NIA NIH HHS/United States ; }, mesh = {Animals ; Humans ; *Microbiota ; Noncommunicable Diseases ; *Social Factors ; *Symbiosis ; Virulence ; }, abstract = {Although social interactions are known to drive pathogen transmission, the contributions of socially transmissible host-associated mutualists and commensals to host health and disease remain poorly explored. We use the concept of the social microbiome-the microbial metacommunity of a social network of hosts-to analyze the implications of social microbial transmission for host health and disease. We investigate the contributions of socially transmissible microbes to both eco-evolutionary microbiome community processes (colonization resistance, the evolution of virulence, and reactions to ecological disturbance) and microbial transmission-based processes (transmission of microbes with metabolic and immune effects, inter-specific transmission, transmission of antibiotic-resistant microbes, and transmission of viruses). We consider the implications of social microbial transmission for communicable and non-communicable diseases and evaluate the importance of a socially transmissible component underlying canonically non-communicable diseases. The social transmission of mutualists and commensals may play a significant, under-appreciated role in the social determinants of health and may act as a hidden force in social evolution.}, }
@article {pmid38174103, year = {2024}, author = {Kantele, A and Paajanen, J and Pietilä, JP and Vapalahti, O and Pakkanen, SH and Lääveri, T}, title = {Long COVID-associated symptoms prevalent in both SARS-CoV-2 positive and negative individuals: A prospective follow-up study.}, journal = {New microbes and new infections}, volume = {56}, number = {}, pages = {101209}, pmid = {38174103}, issn = {2052-2975}, abstract = {BACKGROUND: Research into persistent symptoms among SARS-CoV-2-positive i.e. CoV(+) patients mostly focuses on hospitalized individuals. Our prospective follow-up study compares long COVID-associated symptoms among laboratory-confirmed CoV(+) and SARS-CoV-2 negative [CoV(-)] individuals.<br><br>METHODS: SARS-CoV-2 RT-PCR-tested volunteers were recruited into four cohorts: 1) CoV(+) outpatients, 2) CoV(-) outpatients, 3) CoV(+) intensive care unit (ICU) inpatients, and 4) CoV(+) non-ICU inpatients. Neutralizing antibodies were assessed and questionnaires filled in at enrolment and days 90-120, 121-180, 181-270, 271-365, and 365-533.<br><br>RESULTS: Of the 1326 participants, 1191 were CoV(+): 46 ICU, 123 non-ICU, and 1022 outpatients; 135 were CoV(-) outpatient controls. Both CoV(+) outpatients and CoV(-) controls showed high overall symptom rates at all time points. More prevalent among CoV(+) than CoV(-) outpatients were only impaired olfaction and taste; many others proved more frequent for CoV(-) participants. At &#x2265;181 days, fatigue, dyspnoea, various neuropsychological symptoms and several others were recorded more often for CoV(+) inpatients than outpatients.<br><br>CONCLUSIONS: Long COVID-associated symptoms were more frequent among hospitalized than non-hospitalized CoV(+) participants. As for outpatients, only impaired olfaction and taste showed higher rates in the CoV(+) group; some symptoms proved even more common among those CoV(-). Besides suggesting low long COVID prevalences for outpatients, our results highlight the weight of negative controls.}, }
@article {pmid38172625, year = {2024}, author = {Vill, AC and Rice, EJ and De Vlaminck, I and Danko, CG and Brito, IL}, title = {Precision run-on sequencing (PRO-seq) for microbiome transcriptomics.}, journal = {Nature microbiology}, volume = {9}, number = {1}, pages = {241-250}, pmid = {38172625}, issn = {2058-5276}, support = {R01 GM147731/GM/NIGMS NIH HHS/United States ; R01 HG009309/HG/NHGRI NIH HHS/United States ; R01 HG010346/HG/NHGRI NIH HHS/United States ; }, mesh = {Humans ; *Escherichia coli/genetics ; *RNA, Guide, CRISPR-Cas Systems ; DNA-Directed RNA Polymerases/genetics ; RNA/genetics ; Gene Expression Profiling ; }, abstract = {Bacteria respond to environmental stimuli through precise regulation of transcription initiation and elongation. Bulk RNA sequencing primarily characterizes mature transcripts, so to identify actively transcribed loci we need to capture RNA polymerase (RNAP) complexed with nascent RNA. However, such capture methods have only previously been applied to culturable, genetically tractable organisms such as E. coli and B. subtilis. Here we apply precision run-on sequencing (PRO-seq) to profile nascent transcription in cultured E. coli and diverse uncultured bacteria. We demonstrate that PRO-seq can characterize the transcription of small, structured, or post-transcriptionally modified RNAs, which are often absent from bulk RNA-seq libraries. Applying PRO-seq to the human microbiome highlights taxon-specific RNAP pause motifs and pause-site distributions across non-coding RNA loci that reflect structure-coincident pausing. We also uncover concurrent transcription and cleavage of CRISPR guide RNAs and transfer RNAs. We demonstrate the utility of PRO-seq for exploring transcriptional dynamics in diverse microbial communities.}, }
@article {pmid38170633, year = {2024}, author = {Meynier, M and Daugey, V and Mallaret, G and Gervason, S and Meleine, M and Barbier, J and Aissouni, Y and Lolignier, S and Bonnet, M and Ardid, D and De Vos, WM and Van Hul, M and Suenaert, P and Brochot, A and Cani, PD and Carvalho, FA}, title = {Pasteurized akkermansia muciniphila improves irritable bowel syndrome-like symptoms and related behavioral disorders in mice.}, journal = {Gut microbes}, volume = {16}, number = {1}, pages = {2298026}, pmid = {38170633}, issn = {1949-0984}, mesh = {Maternal Deprivation ; Akkermansia ; *Gastrointestinal Microbiome ; Humans ; *Irritable Bowel Syndrome/therapy ; Animals ; Verrucomicrobia/physiology ; Mice ; }, abstract = {Gut - brain communications disorders in irritable bowel syndrome (IBS) are associated with intestinal microbiota composition, increased gut permeability, and psychosocial disturbances. Symptoms of IBS are difficult to medicate, and hence much research is being made into alternative approaches. This study assesses the potential of a treatment with pasteurized Akkermansia muciniphila for alleviating IBS-like symptoms in two mouse models of IBS with different etiologies. Two clinically relevant animal models were used to mimic IBS-like symptoms in C57BL6/J mice: the neonatal maternal separation (NMS) paradigm and the Citrobacter rodentium infection model. In both models, gut permeability, colonic sensitivity, fecal microbiota composition and colonic IL-22 expression were evaluated. The cognitive performance and emotional state of the animals were also assessed by several tests in the C. rodentium infection model. The neuromodulation ability of pasteurized A. muciniphila was assessed on primary neuronal cells from mice dorsal root ganglia using a ratiometric calcium imaging approach. The administration of pasteurized A. muciniphila significantly reduced colonic hypersensitivity in both IBS mouse models, accompanied by a reinforcement of the intestinal barrier function. Beneficial effects of pasteurized A. muciniphila treatment have also been observed on anxiety-like behavior and memory defects in the C. rodentium infection model. Finally, a neuroinhibitory effect exerted by pasteurized A. muciniphila was observed on neuronal cells stimulated with two algogenic substances such as capsaicin and inflammatory soup. Our findings demonstrate novel anti-hyperalgesic and neuroinhibitory properties of pasteurized A. muciniphila, which therefore may have beneficial effects in relieving pain and anxiety in subjects with IBS.}, }
@article {pmid38168274, year = {2023}, author = {Liu, R and Wang, Y and Cheng, D}, title = {Micro-DeMix: A mixture beta-multinomial model for investigating the fecal microbiome compositions.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {38168274}, issn = {2692-8205}, support = {R01 GM145772/GM/NIGMS NIH HHS/United States ; }, abstract = {Extensive research has uncovered the involvement of the human gut microbiome in various facets of human health, including metabolism, nutrition, physiology, and immune function. Researchers often study fecal microbiota as a proxy for understanding the gut microbiome. However, it has been demonstrated that this approach may not suffice to yield a comprehensive understanding of the entire gut microbial community. Emerging research is revealing the heterogeneity of the gut microbiome across different gastrointestinal (GI) locations in both composition and functions. While spatial metagenomics approach has been developed to address these variations in mice, limitations arise when applying it to human-subject research, primarily due to its invasive nature. With these restrictions, we introduce Micro-DeMix, a mixture beta-multinomial model that decomposes the fecal microbiome at compositional level to understand the heterogeneity of the gut microbiome across various GI locations and extract meaningful insights about the biodiversity of the gut microbiome. Moreover, Micro-DeMix facilitates the discovery of differentially abundant microbes between GI regions through a hypothesis testing framework. We utilize the Inflammatory Bowel Disease (IBD) data from the NIH Integrative Human Microbiome Project to demonstrate the effectiveness and efficiency of the proposed Micro-DeMix.}, }
@article {pmid38166904, year = {2024}, author = {Luan, J and Zhang, F and Suo, L and Zhang, W and Li, Y and Yu, X and Liu, B and Cao, H}, title = {Analyzing lung cancer risks in patients with impaired pulmonary function through characterization of gut microbiome and metabolites.}, journal = {BMC pulmonary medicine}, volume = {24}, number = {1}, pages = {1}, pmid = {38166904}, issn = {1471-2466}, support = {grant no. tsqn202103196//Taishan Scholars Program of Shandong Province/ ; }, mesh = {Humans ; *Gastrointestinal Microbiome ; *Lung Neoplasms ; Metabolomics/methods ; Feces ; Biomarkers ; RNA, Ribosomal, 16S/genetics ; *Multiple Pulmonary Nodules ; }, abstract = {BACKGROUND: Lung cancer (LC) is one of the most devastating diseases worldwide, there is growing studies confirm the role of impaired lung function in LC susceptibility. Moreover, gut microbiota dysbiosis is associated with LC severity. Whether alterations in gut microbiota and metabolites are associated with long-term lung dysfunction in LC patients remain unclear. Our study aimed to analyze the risk factors in LC patients with impaired pulmonary function based on the characteristics of the gut microbiome and metabolites.<br><br>METHODS: Fecal samples from 55 LC patients and 28 benign pulmonary nodules patients were collected. Pulmonary ventilation function was graded according to the American Thoracic Society/ European Respiratory Society (ATS/ERS) method. LC patients were divided into 3 groups, including 20 patients with normal lung ventilation, 23 patients with mild pulmonary ventilation dysfunction and 12 patients with moderate or above pulmonary ventilation dysfunction. The fecal samples were analyzed using 16&#xa0;S rRNA gene amplicon sequencing and metabolomics.<br><br>RESULTS: The gut microbiome composition between LC patients and benign pulmonary nodules patients presented clearly differences based on Partial Least Squares Discriminant Analysis (PLS-DA). Pulmonary ventilation function was positively correlated with LC tumor stage, the richness and diversity of the gut microbiota in LC patients with moderate or above pulmonary ventilation dysfunction increased significantly, characterized by increased abundance of Subdoligranulum and Romboutsia. The metabolomics analysis revealed 69 differential metabolites, which were mainly enriched in beta-Alanine metabolism, styrene degradation and pyrimidine metabolism pathway. The area under the curve (AUC) combining the gut microbiome and metabolites was 90% (95% CI: 79-100%), indicating that the two species and four metabolites might regarded as biomarkers to assess the prediction of LC patients with impaired pulmonary function.<br><br>CONCLUSIONS: Our results showed that microbiome and metabolomics analyses provide important candidate to be used as clinically diagnostic biomarkers and therapeutic targets related to lung cancer with impaired pulmonary function.}, }
@article {pmid38165929, year = {2024}, author = {van Nes, EH and Pujoni, DGF and Shetty, SA and Straatsma, G and de Vos, WM and Scheffer, M}, title = {A tiny fraction of all species forms most of nature: Rarity as a sticky state.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {121}, number = {2}, pages = {e2221791120}, pmid = {38165929}, issn = {1091-6490}, mesh = {Animals ; Humans ; *Ecosystem ; Biodiversity ; Biomass ; *Microbiota ; Trees ; Stochastic Processes ; }, abstract = {Using data from a wide range of natural communities including the human microbiome, plants, fish, mushrooms, rodents, beetles, and trees, we show that universally just a few percent of the species account for most of the biomass. This is in line with the classical observation that the vast bulk of biodiversity is very rare. Attempts to find traits allowing the tiny fraction of abundant species to escape rarity have remained unsuccessful. Here, we argue that this might be explained by the fact that hyper-dominance can emerge through stochastic processes. We demonstrate that in neutrally competing groups of species, rarity tends to become a trap if environmental fluctuations result in gains and losses proportional to abundances. This counter-intuitive phenomenon arises because absolute change tends to zero for very small abundances, causing rarity to become a "sticky state", a pseudoattractor that can be revealed numerically in classical ball-in-cup landscapes. As a result, the vast majority of species spend most of their time in rarity leaving space for just a few others to dominate the neutral community. However, fates remain stochastic. Provided that there is some response diversity, roles occasionally shift as stochastic events or natural enemies bring an abundant species down allowing a rare species to rise to dominance. Microbial time series spanning thousands of generations support this prediction. Our results suggest that near-neutrality within niches may allow numerous rare species to persist in the wings of the dominant ones. Stand-ins may serve as insurance when former key species collapse.}, }
@article {pmid38163940, year = {2023}, author = {Jabłońska-Trypuć, A}, title = {The Role of the Microbiome in Inflammation and Carcinogenesis.}, journal = {Frontiers in bioscience (Elite edition)}, volume = {15}, number = {4}, pages = {28}, doi = {10.31083/j.fbe1504028}, pmid = {38163940}, issn = {1945-0508}, support = {WZ/WB-II&#x15a;/6/2022//Ministry of Education and Science, Poland/ ; }, mesh = {Humans ; *Microbiota/physiology ; Inflammation ; Carcinogenesis ; *Neoplasms ; Tumor Microenvironment ; }, abstract = {Inflammation has been confirmed to exist in the tumor microenvironment, while the risk of cancer occurrence increases in cases of chronic inflammation. It is estimated that approximately 10% to 20% of cancers are associated with chronic infections and attendant inflammation. Bacteria, both pathogenic and commensal, viruses, and fungi actively participate in the development and maintenance of inflammation and tumor growth in humans. The exposome, which is a sum of human environmental exposures, such as industrial diet, consumed drugs, and toxins, affects the composition and function of the human microbiome, which could lead to dysbiosis and disorders in tissue homeostasis through different mechanisms, including the intensification of the immune response, activation and abnormal proliferation, and disruption to epithelial barrier integrity. Presently, science remains at the stage of revealing the complexity associated with the mechanisms involved in building relationships that cover the microbiome-inflammation-tumor, yet it is already known how important it is to care for microbial homeostasis of the organism.}, }
@article {pmid38160303, year = {2024}, author = {Sapoval, N and Tanevski, M and Treangen, TJ}, title = {KombOver: Efficient k-core and K-truss based characterization of perturbations within the human gut microbiome.}, journal = {Pacific Symposium on Biocomputing. Pacific Symposium on Biocomputing}, volume = {29}, number = {}, pages = {506-520}, pmid = {38160303}, issn = {2335-6936}, support = {P01 AI152999/AI/NIAID NIH HHS/United States ; }, mesh = {Humans ; *Gastrointestinal Microbiome ; DNA Copy Number Variations ; Computational Biology ; *Microbiota/genetics ; Metagenome ; Metagenomics/methods ; }, abstract = {The microbes present in the human gastrointestinal tract are regularly linked to human health and disease outcomes. Thanks to technological and methodological advances in recent years, metagenomic sequencing data, and computational methods designed to analyze metagenomic data, have contributed to improved understanding of the link between the human gut microbiome and disease. However, while numerous methods have been recently developed to extract quantitative and qualitative results from host-associated microbiome data, improved computational tools are still needed to track microbiome dynamics with short-read sequencing data. Previously we have proposed KOMB as a de novo tool for identifying copy number variations in metagenomes for characterizing microbial genome dynamics in response to perturbations. In this work, we present KombOver (KO), which includes four key contributions with respect to our previous work: (i) it scales to large microbiome study cohorts, (ii) it includes both k-core and K-truss based analysis, (iii) we provide the foundation of a theoretical understanding of the relation between various graph-based metagenome representations, and (iv) we provide an improved user experience with easier-to-run code and more descriptive outputs/results. To highlight the aforementioned benefits, we applied KO to nearly 1000 human microbiome samples, requiring less than 10 minutes and 10 GB RAM per sample to process these data. Furthermore, we highlight how graph-based approaches such as k-core and K-truss can be informative for pinpointing microbial community dynamics within a myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) cohort. KO is open source and available for download/use at: https://github.com/treangenlab/komb.}, }
@article {pmid38159991, year = {2024}, author = {Ebeling, M and Derka, S and Baudrexl, J and Sakkas, A and Scheurer, M and Wilde, F and Schramm, A and Pietzka, S}, title = {Ibuprofen Reduces 5-Year Overall Survival of Head and Neck Cancer Patients With Immunotherapy - A Retrospective Case-controlled Real-World Data Analysis of 10,000 Patients.}, journal = {Anticancer research}, volume = {44}, number = {1}, pages = {313-322}, doi = {10.21873/anticanres.16814}, pmid = {38159991}, issn = {1791-7530}, mesh = {Humans ; Infant, Newborn ; *Carcinoma/drug therapy ; Cyclooxygenase Inhibitors/adverse effects ; Data Analysis ; *Ductus Arteriosus, Patent/chemically induced/drug therapy ; Ibuprofen/therapeutic use ; Immunotherapy ; Indomethacin ; Infant, Low Birth Weight ; Infant, Premature ; Proton Pump Inhibitors/therapeutic use ; Retrospective Studies ; Case-Control Studies ; }, abstract = {BACKGROUND/AIM: Resistance to immunotherapy can be explained by an abnormal microbiome of the gut. In Europe in particular, the use of ibuprofen, with or without proton-pump inhibitors to protect the gastric mucosa, is widespread. This study aimed to investigate the impact of ibuprofen use on the effectiveness of immunotherapy in patients with head and neck carcinoma.<br><br>PATIENTS AND METHODS: Data from patients with head and neck carcinoma (ICD-10-Codes: C00-C14) receiving pembrolizumab, from the TriNetX network, were analyzed. Two groups were formed for the analyses: Cohort I received ibuprofen at least once within 6 months before and after immunotherapy, whereas patients in cohort II received ibuprofen with proton-pump inhibitors or no ibuprofen at all. Cohorts I and II were matched 1:1 with respect to age, sex, lymph node metastases, nicotine dependence, alcohol dependence, and body mass index (BMI). The primary outcome was death and a Kaplan-Meier analysis was performed, and the risk ratio (RR), odds ratio (OR), and hazard ratio (HR) were calculated.<br><br>RESULTS: The analysis showed that 823 patients with ibuprofen and 724 patients without ibuprofen died within 5 years, showing a significant risk difference of 5.3% (p=0.001). The RR was 1.137 [95% confidence interval (CI)=1.053-1.227], OR was 1.245 (95% CI=1.093-1.418), and HR was 1.202 (95%CI=1.088-1.329).<br><br>CONCLUSION: Ibuprofen significantly decreases the drug effectiveness of immunotherapy and may be related to changes in the human microbiome. However, further prospective, randomized, and double-blind studies are needed to validate our data and to adequately address confounders.}, }
@article {pmid38149262, year = {2023}, author = {Wang, Y and Shojaie, A and Randolph, T and Knight, P and Ma, J}, title = {GENERALIZED MATRIX DECOMPOSITION REGRESSION: ESTIMATION AND INFERENCE FOR TWO-WAY STRUCTURED DATA.}, journal = {The annals of applied statistics}, volume = {17}, number = {4}, pages = {2944-2969}, pmid = {38149262}, issn = {1932-6157}, support = {R01 GM129512/GM/NIGMS NIH HHS/United States ; U19 CA203654/CA/NCI NIH HHS/United States ; T32 GM135117/GM/NIGMS NIH HHS/United States ; R01 GM145772/GM/NIGMS NIH HHS/United States ; P50 CA228944/CA/NCI NIH HHS/United States ; R01 HL155417/HL/NHLBI NIH HHS/United States ; R01 GM133848/GM/NIGMS NIH HHS/United States ; }, abstract = {Motivated by emerging applications in ecology, microbiology, and neuroscience, this paper studies high-dimensional regression with two-way structured data. To estimate the high-dimensional coefficient vector, we propose the generalized matrix decomposition regression (GMDR) to efficiently leverage auxiliary information on row and column structures. GMDR extends the principal component regression (PCR) to two-way structured data, but unlike PCR, GMDR selects the components that are most predictive of the outcome, leading to more accurate prediction. For inference on regression coefficients of individual variables, we propose the generalized matrix decomposition inference (GMDI), a general high-dimensional inferential framework for a large family of estimators that include the proposed GMDR estimator. GMDI provides more flexibility for incorporating relevant auxiliary row and column structures. As a result, GMDI does not require the true regression coefficients to be sparse, but constrains the coordinate system representing the regression coefficients according to the column structure. GMDI also allows dependent and heteroscedastic observations. We study the theoretical properties of GMDI in terms of both the type-I error rate and power and demonstrate the effectiveness of GMDR and GMDI in simulation studies and an application to human microbiome data.}, }
@article {pmid38149226, year = {2023}, author = {Sharifzadeh, SS and Lotfali, E and Lesan, S and Farrokhnia, T}, title = {Antifungal Effect of Probiotic Lactobacillus casei on Drug-Resistant Oral Candida albicans Isolated from Patients with Hematological Malignancy: an in vitro Study.}, journal = {Journal of dentistry (Shiraz, Iran)}, volume = {24}, number = {4}, pages = {389-394}, pmid = {38149226}, issn = {2345-6485}, abstract = {STATEMENT OF THE PROBLEM: Candida albicans (C. albicans) is recognized as the most common opportunistic pathogen in patients with an impaired immune system, and due to the frequent use of antifungal medicine, a variety of drug-resistant species are developing. Probiotics are a part of the human microbiome and natural competitors of Candida by producing lactic acid, low pH, and other secreted metabolites. The role of probiotics in preventing fungal infections has always been discussed.<br><br>PURPOSE: This study aimed to investigate the antifungal effect of Lactobacillus casei (L. casei) on fluconazole- and amphotericin B-resistant C. albicans species isolated from the oral cavity of acute myeloid leukemia patients.<br><br>MATERIALS AND METHOD: In this experimental study, eight strains of fluconazole- and amphotericin B-resistant C. albicans were used. The antifungal effects of probiotic L. casei and nystatin were measured by the co-aggregation method 1, 2, and 4 h after beginning the study. After each hour of exposure, C. albicans and L. casei colonies were counted.<br><br>RESULTS: L. casei had a significant ability to aggregate with both fluconazole- and amphotericin B-resistant C. albicans in all designated intervals, which increased with time. In the first hour of the study, no significant difference was observed between the effects of L. casei on the two drug-resistant strains. However, as time passed, it had a more significant antifungal effect on fluconazole, compared to amphotericin B resistant species (p Value<0.001). Cell counts showed that the number of fungal cells decreased significantly as time passed (p< 0.001).<br><br>CONCLUSION: L. casei had a significant ability to aggregate with both drug-resistant C. albicans species and showed higher antifungal activity on fluconazole-resistant than amphotericin B-resistant species.}, }
@article {pmid38143860, year = {2023}, author = {Peng, C and May, A and Abeel, T}, title = {Unveiling microbial biomarkers of ruminant methane emission through machine learning.}, journal = {Frontiers in microbiology}, volume = {14}, number = {}, pages = {1308363}, pmid = {38143860}, issn = {1664-302X}, abstract = {BACKGROUND: Enteric methane from cow burps, which results from microbial fermentation of high-fiber feed in the rumen, is a significant contributor to greenhouse gas emissions. A promising strategy to address this problem is microbiome-based precision feed, which involves identifying key microorganisms for methane production. While machine learning algorithms have shown success in associating human gut microbiome with various human diseases, there have been limited efforts to employ these algorithms to establish microbial biomarkers for methane emissions in ruminants.<br><br>METHODS: In this study, we aim to identify potential methane biomarkers for methane emission from ruminants by employing regression algorithms commonly used in human microbiome studies, coupled with different feature selection methods. To achieve this, we analyzed the microbiome compositions and identified possible confounding metadata variables in two large public datasets of Holstein cows. Using both the microbiome features and identified metadata variables, we trained different regressors to predict methane emission. With the optimized models, permutation tests were used to determine feature importance to find informative microbial features.<br><br>RESULTS: Among the regression algorithms tested, random forest regression outperformed others and allowed the identification of several crucial microbial taxa for methane emission as members of the native rumen microbiome, including the genera Piromyces, Succinivibrionaceae UCG-002, and Acetobacter. Additionally, our results revealed that certain herd locations and feed composition markers, such as the lipid intake and neutral-detergent fiber intake, are also predictive features for methane emissions.<br><br>CONCLUSION: We demonstrated that machine learning, particularly regression algorithms, can effectively predict cow methane emissions and identify relevant rumen microorganisms. Our findings offer valuable insights for the development of microbiome-based precision feed strategies aiming at reducing methane emissions.}, }
@article {pmid38138045, year = {2023}, author = {Bosch, B and Hartikainen, A and Ronkainen, A and Scheperjans, F and Arkkila, P and Satokari, R}, title = {Development of a Protocol for Anaerobic Preparation and Banking of Fecal Microbiota Transplantation Material: Evaluation of Bacterial Richness in the Cultivated Fraction.}, journal = {Microorganisms}, volume = {11}, number = {12}, pages = {}, pmid = {38138045}, issn = {2076-2607}, support = {6600A-C1012//Finnish National Agency for Education/ ; 323156//Academy of Finland/ ; TYH2019204//The Hospital District of Helsinki and Uusimaa/ ; }, abstract = {Fecal microbiota transplantation (FMT) has shown highly variable results in indications beyond recurrent Clostridioides difficile infection. Microbiota dysbiosis in many diseases is characterized by the depletion of strictly anaerobic bacteria, which may be crucial for FMT efficacy. We developed a protocol to ensure anaerobic conditions during the entire transplant preparation and banking process, from material collection to administration. The protocol necessitates an anaerobic cabinet, i.e., a non-standard laboratory equipment. We analyzed the population of viable anaerobes by combining cultivation and 16S rRNA gene profiling during the transplant preparation, and after 4, 8, and 12 months of anaerobic or aerobic storage at -80 °C, 78% of fecal species were captured via cultivation. Our findings suggest that strictly anaerobic transplant preparation and storage may preserve species richness better than oxic conditions, but the overall difference was not significant. However, specific anaerobes such as Neglecta and Anaerotruncus were affected by the oxygen exposure. A storage time of up to 12 months did not affect the presence of cultivated taxa. Noteworthy, our analysis focused on the richness of cultivated anaerobes rather than their abundance, which may have been affected. The benefits of the developed anaerobic protocol in FMT for specific indications remain to be demonstrated in clinical trials.}, }
@article {pmid38135286, year = {2023}, author = {Angkananard, T}, title = {The Human Microbiome and Atherosclerotic Coronary Heart Disease.}, journal = {European journal of preventive cardiology}, volume = {}, number = {}, pages = {}, doi = {10.1093/eurjpc/zwad401}, pmid = {38135286}, issn = {2047-4881}, }
@article {pmid38132866, year = {2023}, author = {Cheddadi, R and Yeramilli, V and Martin, C}, title = {From Mother to Infant, from Placenta to Gut: Understanding Varied Microbiome Profiles in Neonates.}, journal = {Metabolites}, volume = {13}, number = {12}, pages = {}, pmid = {38132866}, issn = {2218-1989}, abstract = {The field of human microbiome and gut microbial diversity research has witnessed a profound transformation, driven by advances in omics technologies. These advancements have unveiled essential connections between microbiome alterations and severe conditions, prompting the development of new frameworks through epidemiological studies. Traditionally, it was believed that each individual harbored unique microbial communities acquired early in life, evolving over the course of their lifetime, with little acknowledgment of any prenatal microbial development, but recent research challenges this belief. The neonatal microbiome's onset, influenced by factors like delivery mode and maternal health, remains a subject of intense debate, hinting at potential intrauterine microbial processes. In-depth research reveals associations between microbiome profiles and specific health outcomes, ranging from obesity to neurodevelopmental disorders. Understanding these diverse microbiome profiles is essential for unraveling the intricate relationships between the microbiome and health outcomes.}, }
@article {pmid38132864, year = {2023}, author = {Bartsch, M and Hahn, A and Berkemeyer, S}, title = {Bridging the Gap from Enterotypes to Personalized Dietary Recommendations: A Metabolomics Perspective on Microbiome Research.}, journal = {Metabolites}, volume = {13}, number = {12}, pages = {}, pmid = {38132864}, issn = {2218-1989}, abstract = {Advances in high-throughput DNA sequencing have propelled research into the human microbiome and its link to metabolic health. We explore microbiome analysis methods, specifically emphasizing metabolomics, how dietary choices impact the production of microbial metabolites, providing an overview of studies examining the connection between enterotypes and diet, and thus, improvement of personalized dietary recommendations. Acetate, propionate, and butyrate constitute more than 95% of the collective pool of short-chain fatty acids. Conflicting data on acetate's effects may result from its dynamic signaling, which can vary depending on physiological conditions and metabolic phenotypes. Human studies suggest that propionate has overall anti-obesity effects due to its well-documented chemistry, cellular signaling mechanisms, and various clinical benefits. Butyrate, similar to propionate, has the ability to reduce obesity by stimulating the release of appetite-suppressing hormones and promoting the synthesis of leptin. Tryptophan affects systemic hormone secretion, with indole stimulating the release of GLP-1, which impacts insulin secretion, appetite suppression, and gastric emptying. Bile acids, synthesized from cholesterol in the liver and subsequently modified by gut bacteria, play an essential role in the digestion and absorption of dietary fats and fat-soluble vitamins, but they also interact directly with intestinal microbiota and their metabolites. One study using statistical methods identified primarily two groupings of enterotypes Bacteroides and Ruminococcus. The Prevotella-dominated enterotype, P-type, in humans correlates with vegetarians, high-fiber and carbohydrate-rich diets, and traditional diets. Conversely, individuals who consume diets rich in animal fats and proteins, typical in Western-style diets, often exhibit the Bacteroides-dominated, B-type, enterotype. The P-type showcases efficient hydrolytic enzymes for plant fiber degradation but has limited lipid and protein fermentation capacity. Conversely, the B-type features specialized enzymes tailored for the degradation of animal-derived carbohydrates and proteins, showcasing an enhanced saccharolytic and proteolytic potential. Generally, models excel at predictions but often struggle to fully elucidate why certain substances yield varied responses. These studies provide valuable insights into the potential for personalized dietary recommendations based on enterotypes.}, }
@article {pmid38132480, year = {2023}, author = {Kim, MJ and Ko, H and Kim, JY and Kim, HJ and Kim, HY and Cho, HE and Cho, HD and Seo, WS and Kang, HC}, title = {Improvement in Yield of Extracellular Vesicles Derived from Edelweiss Callus Treated with LED Light and Enhancement of Skin Anti-Aging Indicators.}, journal = {Current issues in molecular biology}, volume = {45}, number = {12}, pages = {10159-10178}, pmid = {38132480}, issn = {1467-3045}, abstract = {The process of skin aging is currently recognized as a disease, and extracellular vesicles (EVs) are being used to care for it. While various EVs are present in the market, there is a growing need for research on improving skin conditions through microbial and plant-derived EVs. Edelweiss is a medicinal plant and is currently an endangered species. Callus culture is a method used to protect rare medicinal plants, and recently, research on EVs using callus culture has been underway. In this study, the researchers used LED light to increase the productivity of Edelweiss EVs and confirmed that productivity was enhanced by LED exposure. Additionally, improvements in skin anti-aging indicators were observed. Notably, M-LED significantly elevated callus fresh and dry weight, with a DW/FW ratio of 4.11%, indicating enhanced proliferation. Furthermore, M-LED boosted secondary metabolite production, including a 20% increase in total flavonoids and phenolics. The study explores the influence of M-LED on EV production, revealing a 2.6-fold increase in concentration compared to darkness. This effect is consistent across different plant species (Centella asiatica, Panax ginseng), demonstrating the universality of the phenomenon. M-LED-treated EVs exhibit a concentration-dependent inhibition of reactive oxygen species (ROS) production, surpassing dark-cultured EVs. Extracellular melanin content analysis reveals M-LED-cultured EVs' efficacy in reducing melanin production. Additionally, the expression of key skin proteins (FLG, AQP3, COL1) is significantly higher in fibroblasts treated with M-LED-cultured EVs. These results are expected to provide valuable insights into research on improving the productivity of plant-derived EVs and enhancing skin treatment using plant-derived EVs.}, }
@article {pmid38127919, year = {2023}, author = {L'Heureux, JE and van der Giezen, M and Winyard, PG and Jones, AM and Vanhatalo, A}, title = {Localisation of nitrate-reducing and highly abundant microbial communities in the oral cavity.}, journal = {PloS one}, volume = {18}, number = {12}, pages = {e0295058}, pmid = {38127919}, issn = {1932-6203}, mesh = {Humans ; *Nitrates/metabolism ; Nitrogen Dioxide ; Mouth/microbiology ; Bacteria ; Saliva/metabolism ; *Microbiota ; Streptococcus ; }, abstract = {The nitrate (NO3-) reducing bacteria resident in the oral cavity have been implicated as key mediators of nitric oxide (NO) homeostasis and human health. NO3--reducing oral bacteria reduce inorganic dietary NO3- to nitrite (NO2-) via the NO3--NO2--NO pathway. Studies of oral NO3--reducing bacteria have typically sampled from either the tongue surface or saliva. The aim of this study was to assess whether other areas in the mouth could contain a physiologically relevant abundance of NO3- reducing bacteria, which may be important for sampling in clinical studies. The bacterial composition of seven oral sample types from 300 individuals were compared using a meta-analysis of the Human Microbiome Project data. This analysis revealed significant differences in the proportions of 20 well-established oral bacteria and highly abundant NO3--reducing bacteria across each oral site. The genera included Actinomyces, Brevibacillus, Campylobacter, Capnocytophaga, Corynebacterium, Eikenella, Fusobacterium, Granulicatella, Haemophilus, Leptotrichia, Microbacterium, Neisseria, Porphyromonas, Prevotella, Propionibacterium, Rothia, Selenomonas, Staphylococcus, Streptococcus and Veillonella. The highest proportion of NO3--reducing bacteria was observed in saliva, where eight of the bacterial genera were found in higher proportion than on the tongue dorsum, whilst the lowest proportions were found in the hard oral surfaces. Saliva also demonstrated higher intra-individual variability and bacterial diversity. This study provides new information on where samples should be taken in the oral cavity to assess the abundance of NO3--reducing bacteria. Taking saliva samples may benefit physiological studies, as saliva contained the highest abundance of NO3- reducing bacteria and is less invasive than other sampling methods. These results inform future studies coupling oral NO3--reducing bacteria research with physiological outcomes affecting human health.}, }
@article {pmid38126017, year = {2023}, author = {Gätjens-Boniche, O and Jiménez-Madrigal, JP and Whetten, RW and Valenzuela-Diaz, S and Alemán-Gutiérrez, A and Hanson, PE and Pinto-Tomás, AA}, title = {Microbiome and plant cell transformation trigger insect gall induction in cassava.}, journal = {Frontiers in plant science}, volume = {14}, number = {}, pages = {1237966}, pmid = {38126017}, issn = {1664-462X}, abstract = {Several specialised insects can manipulate normal plant development to induce a highly organised structure known as a gall, which represents one of the most complex interactions between insects and plants. Thus far, the mechanism for insect-induced plant galls has remained elusive. To study the induction mechanism of insect galls, we selected the gall induced by Iatrophobia brasiliensis (Diptera: Cecidomyiidae) in cassava (Euphorbiaceae: Manihot esculenta Crantz) as our model. PCR-based molecular markers and deep metagenomic sequencing data were employed to analyse the gall microbiome and to test the hypothesis that gall cells are genetically transformed by insect vectored bacteria. A shotgun sequencing discrimination approach was implemented to selectively discriminate between foreign DNA and the reference host plant genome. Several known candidate insertion sequences were identified, the most significant being DNA sequences found in bacterial genes related to the transcription regulatory factor CadR, cadmium-transporting ATPase encoded by the cadA gene, nitrate transport permease protein (nrtB gene), and arsenical pump ATPase (arsA gene). In addition, a DNA fragment associated with ubiquitin-like gene E2 was identified as a potential accessory genetic element involved in gall induction mechanism. Furthermore, our results suggest that the increased quality and rapid development of gall tissue are mostly driven by microbiome enrichment and the acquisition of critical endophytes. An initial gall-like structure was experimentally obtained in M. esculenta cultured tissues through inoculation assays using a Rhodococcus bacterial strain that originated from the inducing insect, which we related to the gall induction process. We provide evidence that the modification of the endophytic microbiome and the genetic transformation of plant cells in M. esculenta are two essential requirements for insect-induced gall formation. Based on these findings and having observed the same potential DNA marker in galls from other plant species (ubiquitin-like gene E2), we speculate that bacterially mediated genetic transformation of plant cells may represent a more widespread gall induction mechanism found in nature.}, }
@article {pmid38123504, year = {2024}, author = {Patjas, A and Martelius, A and Ollgren, J and Kantele, A}, title = {International travel increases risk of urinary tract infection caused by extended-spectrum beta-lactamase-producing Enterobacterales-three-arm case-control study.}, journal = {Journal of travel medicine}, volume = {31}, number = {1}, pages = {}, doi = {10.1093/jtm/taad155}, pmid = {38123504}, issn = {1708-8305}, support = {//Sigrid Juselius Foundation/ ; TYH2021314//Finnish Governmental Subsidy for Health Science Research/ ; //University of Helsinki Doctoral School/ ; }, mesh = {Female ; Humans ; Male ; Anti-Bacterial Agents/therapeutic use ; beta-Lactamases ; Case-Control Studies ; Escherichia coli ; *Escherichia coli Infections/drug therapy ; Risk Factors ; *Urinary Tract Infections/drug therapy/epidemiology ; }, abstract = {BACKGROUND: Extended-spectrum beta-lactamase-producing Enterobacterales (ESBL-PE) have worldwide become increasingly prevalent as pathogens causing urinary tract infections (UTIs), posing challenges in their treatment. Of particular concern are travellers to low- and middle-income countries (LMICs), a substantial proportion of whom become colonized by ESBL-PE, with UTIs as the most common clinical manifestation. Seeking tools for preventing ESBL-PE UTI, we explored factors associated with (i) any UTI (versus control), (ii) ESBL-PE UTI (versus control) and (iii) ESBL-PE versus non-ESBL-PE UTI.<br><br>METHODS: During 2015-20, we recruited patients with recent ESBL-PE or non-ESBL-PE UTIs, and controls with no UTI to fill in questionnaires covering potential (ESBL-PE-)UTI risk factors.<br><br>RESULTS: Of our 430 participants, 130 had ESBL-PE UTI and 187 non-ESBL-PE UTI; 113 were controls. Our three comparisons showed several risk factors as exemplified for any UTI versus controls by female sex, lower education, age, diabetes, antibiotic use, diarrhoea; for ESBL-PE UTI versus controls by travel to LMICs, antibiotic use, swimming; and ESBL-PE versus non-ESBL-PE UTI by male sex, higher education, LMIC travel (participant/household member), pets and antibiotic use. Weekly fish meals appeared protective against both UTI and ESBL-PE UTI.<br><br>CONCLUSIONS: Of the numerous factors predisposing to UTI and/or ESBL-PE UTI, our study highlights antibiotic use and LMIC travel. Household members' LMIC travel appears to pose a risk of ESBL-PE UTI, pointing to household transmission of travel-acquired uropathogens. As predisposing factors to multidrug-resistant UTI, international travel and antibiotic use constitute practical targets for prevention efforts.}, }
@article {pmid38116074, year = {2024}, author = {Sheng, Y and Wang, J and Gao, Y and Peng, Y and Li, X and Huang, W and Zhou, H and Liu, R and Zhang, W}, title = {Combined analysis of cross-population healthy adult human microbiome reveals consistent differences in gut microbial characteristics between Western and non-Western countries.}, journal = {Computational and structural biotechnology journal}, volume = {23}, number = {}, pages = {87-95}, pmid = {38116074}, issn = {2001-0370}, abstract = {Despite extensive research on the gut microbiome of healthy individuals from a single country, there are still a limited number of population-level comparative studies. Moreover, the sequencing approach used in most related studies involves 16 S ribosomal RNA (rRNA) sequencing with a limited resolution, which cannot provide detailed functional profiles. In the present study, we applied a combined analysis approach to analyze whole metagenomic shotgun sequencing data from 2035 healthy adult samples from six countries across four continents. Analysis of core species revealed that 13 species were present in more than 90 % of all investigated individuals, the majority of which produced short-chain fatty acids (SCFA)-producing bacteria. Our analysis revealed consistently significant differences in gut microbial species and pathways between Western and non-Western countries, such as Escherichia coli and the relation of MetaCyc pathways to the TCA cycle. Specific changes in microbial species and pathways are potentially related to lifestyle and diet. Furthermore, we identified several noteworthy microbial species and pathways that exhibit distinct characteristics specific to China. Interestingly, we observed that China (CHN) was more similar to the United States (USA) and United Kingdom (GBR) in terms of the taxonomic and functional composition of the gut microbiome than India (IND) and Madagascar (MDG), which were more similar to the China (CHN) diet. The current study identified consistent microbial features associated with population and geography, which will inspire further clinical translations that consider paying attention to differences in microbiota backgrounds and confounding factors.}, }
@article {pmid38111603, year = {2023}, author = {Rowley, CE and Lodge, S and Egan, S and Itsiopoulos, C and Christophersen, CT and Silva, D and Kicic-Starcevich, E and O'Sullivan, TA and Wist, J and Nicholson, J and Frost, G and Holmes, E and D'Vaz, N}, title = {Altered dietary behaviour during pregnancy impacts systemic metabolic phenotypes.}, journal = {Frontiers in nutrition}, volume = {10}, number = {}, pages = {1230480}, pmid = {38111603}, issn = {2296-861X}, abstract = {RATIONALE: Evidence suggests consumption of a Mediterranean diet (MD) can positively impact both maternal and offspring health, potentially mediated by a beneficial effect on inflammatory pathways. We aimed to apply metabolic profiling of serum and urine samples to assess differences between women who were stratified into high and low alignment to a MD throughout pregnancy and investigate the relationship of the diet to inflammatory markers.<br><br>METHODS: From the ORIGINS cohort, 51 pregnant women were stratified for persistent high and low alignment to a MD, based on validated MD questionnaires. [1]H Nuclear Magnetic Resonance (NMR) spectroscopy was used to investigate the urine and serum metabolite profiles of these women at 36&#x2009;weeks of pregnancy. The relationship between diet, metabolite profile and inflammatory status was investigated.<br><br>RESULTS: There were clear differences in both the food choice and metabolic profiles of women who self-reported concordance to a high (HMDA) and low (LMDA) Mediterranean diet, indicating that alignment with the MD was associated with a specific metabolic phenotype during pregnancy. Reduced meat intake and higher vegetable intake in the HMDA group was supported by increased levels of urinary hippurate (p&#x2009;=&#x2009;0.044) and lower creatine (p&#x2009;=&#x2009;0.047) levels. Serum concentrations of the NMR spectroscopic inflammatory biomarkers GlycA (p&#x2009;=&#x2009;0.020) and GlycB (p&#x2009;=&#x2009;0.016) were significantly lower in the HDMA group and were negatively associated with serum acetate, histidine and isoleucine (p&#x2009;<&#x2009;0.05) suggesting a greater level of plant-based nutrients in the diet. Serum branched chain and aromatic amino acids were positively associated with the HMDA group while both urinary and serum creatine, urine creatinine and dimethylamine were positively associated with the LMDA group.<br><br>CONCLUSION: Metabolic phenotypes of pregnant women who had a high alignment with the MD were significantly different from pregnant women who had a poor alignment with the MD. The metabolite profiles aligned with reported food intake. Differences were most significant biomarkers of systemic inflammation and selected gut-microbial metabolites. This research expands our understanding of the mechanisms driving health outcomes during the perinatal period and provides additional biomarkers for investigation in pregnant women to assess potential health risks.}, }
@article {pmid38108668, year = {2024}, author = {Ye, H-L and Zhi, M-F and Chen, B-Y and Lin, W-Z and Li, Y-L and Huang, S-J and Zhou, L-J and Xu, S and Zhang, J and Zhang, W-C and Feng, Q and Duan, S-Z}, title = {Alterations of oral and gut viromes in hypertension and/or periodontitis.}, journal = {mSystems}, volume = {9}, number = {1}, pages = {e0116923}, pmid = {38108668}, issn = {2379-5077}, support = {81991503 81725003 81921002//MOST | National Natural Science Foundation of China (NSFC)/ ; SHSMU-ZDCX20212500//Innovative Research Team of High-level Local University in Shanghai (Innovative Research Team of High-level Local Universities in Shanghai)/ ; }, mesh = {Humans ; Virome ; *Viruses/genetics ; *Microbiota/genetics ; *Periodontitis ; *Hypertension ; }, abstract = {The microbiota plays an important role in both hypertension (HTN) and periodontitis (PD), and PD exacerbates the development of HTN by oral and gut microbiota. Previous studies have focused on exploring the importance of the bacteriome in HTN and PD but overlooked the impact of the virome, which is also a member of the microbiota. We collected 180 samples of subgingival plaques, saliva, and feces from a cohort of healthy subjects (nHTNnPD), subjects with HTN (HTNnPD) or PD (PDnHTN), and subjects with both HTN and PD (HTNPD). We performed metagenomic sequencing to assess the roles of the oral and gut viromes in HTN and PD. The HTNnPD, PDnHTN, and HTNPD groups all showed significantly distinct beta diversity from the nHTNnPD group in saliva. We analyzed alterations in oral and gut viral composition in HTN and/or PD and identified significantly changed viruses in each group. Many viruses across three sites were significantly associated with blood pressure and other clinical parameters. Combined with these clinical associations, we found that Gillianvirus in subgingival plaques was negatively associated with HTN and that Torbevirus in saliva was positively associated with HTN. We found that Pepyhexavirus from subgingival plaques was indicated to be transferred to the gut. We finally evaluated viral-bacterial transkingdom interactions and found that viruses and bacteria may cooperate to affect HTN and PD. Correspondingly, HTN and PD may synergize to improve communications between viruses and bacteria.IMPORTANCEPeriodontitis (PD) and hypertension (HTN) are both highly prevalent worldwide and cause serious adverse outcomes. Increasing studies have shown that PD exacerbates HTN by oral and gut microbiota. Previous studies have focused on exploring the importance of the bacteriome in HTN and PD but overlooked the impact of the virome, even though viruses are common inhabitants in humans. Alterations in oral and gut viral diversity and composition contribute to diseases. The present study, for the first time, profiled the oral and gut viromes in HTN and/or PD. We identified key indicator viruses and their clinical implications in HTN and/or PD. We also investigated interactions between viruses and bacteria. This work improved the overall understanding of the viromes in HTN and PD, providing vital insights into the role of the virome in the development of HTN and PD.}, }
@article {pmid38107520, year = {2023}, author = {Fenneman, AC and van der Spek, AH and Hartstra, A and Havik, S and Salonen, A and de Vos, WM and Soeters, MR and Saeed, P and Nieuwdorp, M and Rampanelli, E}, title = {Intestinal permeability is associated with aggravated inflammation and myofibroblast accumulation in Graves' orbitopathy: the MicroGO study.}, journal = {Frontiers in endocrinology}, volume = {14}, number = {}, pages = {1173481}, pmid = {38107520}, issn = {1664-2392}, mesh = {Humans ; *Graves Ophthalmopathy/metabolism ; Myofibroblasts ; Receptors, Thyrotropin ; Intestinal Barrier Function ; Toll-Like Receptor 5/metabolism ; Toll-Like Receptor 9/metabolism ; *Graves Disease/metabolism ; Inflammation ; }, abstract = {BACKGROUND: Graves' disease (GD) and Graves' orbitopathy (GO) result from ongoing stimulation of the TSH receptor due to autoantibodies acting as persistent agonists. Orbital pre-adipocytes and fibroblasts also express the TSH receptor, resulting in expanded retro-orbital tissue and causing exophthalmos and limited eye movement. Recent studies have shown that GD/GO patients have a disturbed gut microbiome composition, which has been associated with increased intestinal permeability. This study hypothesizes that enhanced intestinal permeability may aggravate orbital inflammation and, thus, increase myofibroblast differentiation and the degree of fibrosis.<br><br>METHODS: Two distinct cohorts of GO patients were studied, one of which was a unique cohort consisting of blood, fecal, and retro-orbital tissue samples. Intestinal permeability was assessed by measuring serum lipopolysaccharide-binding protein (LBP), zonulin, TLR5, and TLR9 ligands. The influx of macrophages and accumulation of T-cells and myofibroblast were quantified in orbital connective tissue. The NanoString immune-oncology RNA targets panel was used to determine the transcriptional profile of active fibrotic areas within orbital sections.<br><br>RESULTS: GO patients displayed significantly higher LBP serum concentrations than healthy controls. Within the MicroGO cohort, patients with high serum LBP levels also showed higher levels of zonulin and TLR5 and TLR9 ligands in their circulation. The increased intestinal permeability was accompanied by augmented expression of genes marking immune cell infiltration and encoding key proteins for immune cell adhesion, antigen presentation, and cytokine signaling in the orbital tissue. Macrophage influx was positively linked to the extent of T cell influx and fibroblast activation within GO-affected orbital tissues. Moreover, serum LBP levels significantly correlated with the abundance of specific Gram-negative gut bacteria, linking the gut to local orbital inflammation.<br><br>CONCLUSION: These results indicate that GO patients have enhanced intestinal permeability. The subsequent translocation of bacterial compounds to the systemic circulation may aggravate inflammatory processes within the orbital tissue and, as a consequence, augment the proportion of activated myofibroblasts, which actively secrete extracellular matrix leading to retro-orbital tissue expansion. These findings warrant further exploration to assess the correlation between specific inflammatory pathways in the orbital tissue and the gut microbiota composition and may pave the way for new microbiota-targeting therapies.}, }
@article {pmid38101449, year = {2023}, author = {Vanstokstraeten, R and Demuyser, T and Piérard, D and Wybo, I and Blockeel, C and Mackens, S}, title = {Culturomics in Unraveling the Upper Female Reproductive Tract Microbiota.}, journal = {Seminars in reproductive medicine}, volume = {41}, number = {5}, pages = {151-159}, doi = {10.1055/s-0043-1777758}, pmid = {38101449}, issn = {1526-4564}, mesh = {Female ; Humans ; *Genitalia, Female ; *Microbiota ; Endometrium ; Embryo Implantation ; }, abstract = {In recent years, the study of the human microbiome has surged, shedding light on potential connections between microbiome composition and various diseases. One specific area of intense interest within this research is the female reproductive tract, as it holds the potential to influence the process of embryo implantation. Advanced sequencing technologies have delivered unprecedented insights into the microbial communities, also known as microbiota, residing in the female reproductive tract. However, their efficacy encounters significant challenges when analyzing low-biomass microbiota, such as those present in the endometrium. These molecular techniques are susceptible to contamination from laboratory reagents and extraction kits, leading to sequencing bias that can significantly alter the perceived taxonomy of a sample. Consequently, investigating the microbiota of the upper female reproductive tract necessitates the exploration of alternative methods. In this context, the current review delves into the application of culturomics in unraveling the upper female reproductive tract microbiota. While culturomics holds value in research, its transition to routine clinical practice appears remote, at least in the foreseeable future.}, }
@article {pmid38099679, year = {2024}, author = {Souza, CE and Jacobson, NE and An, MA and Droit, L and Vega, AA and Rosales, M and Mihindukulasuriya, KA and Pastrana, K and Handley, SA and Parkes, M and Rimmer, J and Wang, D and Dinsdale, EA and A Edwards, R and Segall, AM}, title = {Draft genomes of 12 Bifidobacterium isolates from human IBD fecal samples.}, journal = {Microbiology resource announcements}, volume = {13}, number = {1}, pages = {e0013023}, pmid = {38099679}, issn = {2576-098X}, support = {RC2 DK116713/DK/NIDDK NIH HHS/United States ; }, abstract = {Twelve Bifidobacterium strains were isolated from fecal samples of inflammatory bowel disease patients and matched "household control" individuals. These include the species Bifidobacterium adolescentis, Bifidobacterium animalis, Bifidobacterium breve, Bifidobacterium catenulatum, Bifidobacterium longum, and Bifidobacterium pseudocatenulatum.}, }
@article {pmid38098667, year = {2023}, author = {Chung, Y and Kang, SB and Son, D and Lee, JY and Chung, MJ and Lim, S}, title = {Characterization of the probiotic properties of Lacticaseibacillus rhamnosus LR6 isolated from the vaginas of healthy Korean women against vaginal pathogens.}, journal = {Frontiers in microbiology}, volume = {14}, number = {}, pages = {1308293}, pmid = {38098667}, issn = {1664-302X}, abstract = {The human microbiome exhibits intricate populations across the body, with the vaginal tract serving as an ecosystem characterized by the prevalence of the genus Lactobacillus. Disruptions in the vaginal microbiota, which are frequently linked to variables such as sexual activity, hormonal fluctuations, and excessive use of antibiotics, can result in vaginal dysbiosis and the development of diseases such as bacterial vaginosis (BV) and candidiasis. Lactobacillus species, owing to their capacity to create an acidic environment through the production of lactic acid, have a key function within this complex microbial community: they inhibit the growth of harmful microorganisms. This study aimed to investigate the genomic characteristics of L. rhamnosus LR6, a newly discovered strain isolated from the vaginal microbiota of 20 healthy women to assess its potential as a vaginal probiotic. We performed a comparative investigation of the genetic traits of L. rhamnosus using 45 publicly available genomes from various sources. We evaluated the genetic characteristics related to carbohydrate utilization, adhesion to host cells, and the presence of bacteriocin clusters. A comprehensive study was conducted by integrating in silico evaluations with experimental techniques to authenticate the physiological characteristics of strain LR6. We further used a rat model to assess the impact of L. rhamnosus LR6 administration on the changes in the gastrointestinal tract and the vaginal microbiome. The assessments revealed a significantly high inhibitory activity against pathogens, enhanced adherence to host cells, and high lactic acid production. Rat experiments revealed changes in both the fecal and vaginal microbiota; in treated rats, Firmicutes increased in both; Lactobacillaceae increased in the fecal samples; and Enterobacteriaceae decreased but Enterococcaceae, Streptococcaceae, and Morganellaceae increased in the vaginal samples. The study results provide evidence of the genetic characteristics and probiotic properties of LR6, and suggest that oral administration of L. rhamnosus LR6 can alter both gut and vaginal microbiome. Collectively, these findings establish L. rhamnosus LR6 as a highly promising candidate for improving vaginal health.}, }
@article {pmid38097930, year = {2023}, author = {Lu, S and Liang, Y and Li, L and Miao, R and Liao, S and Zou, Y and Yang, C and Ouyang, D}, title = {Predicting potential microbe-disease associations based on auto-encoder and graph convolution network.}, journal = {BMC bioinformatics}, volume = {24}, number = {1}, pages = {476}, pmid = {38097930}, issn = {1471-2105}, support = {No.2022KY0608//Young and Middle aged Teachers Research Basic Ability Improvement Project of Guangxi Universities/ ; No.0056/2020/AFJ//Macau Science and Technology Development Funds Grant No.0056/2020/AFJ from the Macau Special Administrative Region of the People's Republic of China/ ; }, mesh = {Humans ; *Algorithms ; Computational Biology/methods ; *Neoplasms ; }, abstract = {The increasing body of research has consistently demonstrated the intricate correlation between the human microbiome and human well-being. Microbes can impact the efficacy and toxicity of drugs through various pathways, as well as influence the occurrence and metastasis of tumors. In clinical practice, it is crucial to elucidate the association between microbes and diseases. Although traditional biological experiments accurately identify this association, they are time-consuming, expensive, and susceptible to experimental conditions. Consequently, conducting extensive biological experiments to screen potential microbe-disease associations becomes challenging. The computational methods can solve the above problems well, but the previous computational methods still have the problems of low utilization of node features and the prediction accuracy needs to be improved. To address this issue, we propose the DAEGCNDF model predicting potential associations between microbes and diseases. Our model calculates four similar features for each microbe and disease. These features are fused to obtain a comprehensive feature matrix representing microbes and diseases. Our model first uses the graph convolutional network module to extract low-rank features with graph information of microbes and diseases, and then uses a deep sparse Auto-Encoder to extract high-rank features of microbe-disease pairs, after which the low-rank and high-rank features are spliced to improve the utilization of node features. Finally, Deep Forest was used for microbe-disease potential relationship prediction. The experimental results show that combining low-rank and high-rank features helps to improve the model performance and Deep Forest has better classification performance than the baseline model.}, }
@article {pmid38095449, year = {2024}, author = {Arehart, CH and Sterrett, JD and Garris, RL and Quispe-Pilco, RE and Gignoux, CR and Evans, LM and Stanislawski, MA}, title = {Poly-omic risk scores predict inflammatory bowel disease diagnosis.}, journal = {mSystems}, volume = {9}, number = {1}, pages = {e0067723}, pmid = {38095449}, issn = {2379-5077}, support = {K01 HL157658/HL/NHLBI NIH HHS/United States ; P30 DK048520/DK/NIDDK NIH HHS/United States ; T32 MH016880/MH/NIMH NIH HHS/United States ; }, mesh = {Humans ; *Inflammatory Bowel Diseases/diagnosis ; Metagenomics/methods ; Phenotype ; *Microbiota ; Risk Factors ; }, abstract = {Inflammatory bowel disease (IBD) is characterized by complex etiology and a disrupted colonic ecosystem. We provide a framework for the analysis of multi-omic data, which we apply to study the gut ecosystem in IBD. Specifically, we train and validate models using data on the metagenome, metatranscriptome, virome, and metabolome from the Human Microbiome Project 2 IBD multi-omic database, with 1,785 repeated samples from 130 individuals (103 cases and 27 controls). After splitting the participants into training and testing groups, we used mixed-effects least absolute shrinkage and selection operator regression to select features for each omic. These features, with demographic covariates, were used to generate separate single-omic prediction scores. All four single-omic scores were then combined into a final regression to assess the relative importance of the individual omics and the predictive benefits when considered together. We identified several species, pathways, and metabolites known to be associated with IBD risk, and we explored the connections between data sets. Individually, metabolomic and viromic scores were more predictive than metagenomics or metatranscriptomics, and when all four scores were combined, we predicted disease diagnosis with a Nagelkerke's R[2] of 0.46 and an area under the curve of 0.80 (95% confidence interval: 0.63, 0.98). Our work supports that some single-omic models for complex traits are more predictive than others, that incorporating multiple omic data sets may improve prediction, and that each omic data type provides a combination of unique and redundant information. This modeling framework can be extended to other complex traits and multi-omic data sets.IMPORTANCEComplex traits are characterized by many biological and environmental factors, such that multi-omic data sets are well-positioned to help us understand their underlying etiologies. We applied a prediction framework across multiple omics (metagenomics, metatranscriptomics, metabolomics, and viromics) from the gut ecosystem to predict inflammatory bowel disease (IBD) diagnosis. The predicted scores from our models highlighted key features and allowed us to compare the relative utility of each omic data set in single-omic versus multi-omic models. Our results emphasized the importance of metabolomics and viromics over metagenomics and metatranscriptomics for predicting IBD status. The greater predictive capability of metabolomics and viromics is likely because these omics serve as markers of lifestyle factors such as diet. This study provides a modeling framework for multi-omic data, and our results show the utility of combining multiple omic data types to disentangle complex disease etiologies and biological signatures.}, }
@article {pmid38094244, year = {2023}, author = {Wijdeveld, M and Schrantee, A and Hagemeijer, A and Nederveen, AJ and Scheithauer, TPM and Levels, JHM and Prodan, A and de Vos, WM and Nieuwdorp, M and Ijzerman, RG}, title = {Intestinal acetate and butyrate availability is associated with glucose metabolism in healthy individuals.}, journal = {iScience}, volume = {26}, number = {12}, pages = {108478}, pmid = {38094244}, issn = {2589-0042}, abstract = {Animal studies suggest that short-chain fatty acids acetate and butyrate are key players in the gut-brain axis and may affect insulin sensitivity. We investigated the association of intestinal acetate and butyrate availability (measured by butyryl-coenzyme A transferase (ButCoA) gene amount) with insulin sensitivity and secretion in healthy subjects from the HELIUS cohort study from the highest 15% (N = 30) and the lowest 15% (N = 30) intestinal ButCoA gene amount. The groups did not differ in insulin sensitivity or secretion. However, the high ButCoA group showed lower glucose and insulin peaks during the first 60 min after a meal and a higher nadir during the second 60 min (p < 0.01), suggesting delayed glucose adsorption from the small intestine. Our data suggest that chronically increased acetate and butyrate availability may improve glucose metabolism by delaying gastric emptying and intestinal adsorption. Future studies should further investigate the effect of acetate and butyrate interventions.}, }
@article {pmid38088868, year = {2024}, author = {Zhao, Z and Sun, X and Cao, L and Zhu, C and He, K and Hu, X and Liu, C and Feng, Q and Qin, Y}, title = {Salivary Proteome and Intact N-Glycopeptides Analysis Reveal Specific Signatures in Periodontitis.}, journal = {Journal of proteome research}, volume = {23}, number = {1}, pages = {25-39}, doi = {10.1021/acs.jproteome.3c00253}, pmid = {38088868}, issn = {1535-3907}, mesh = {Humans ; Proteome/genetics/metabolism ; *Diabetes Mellitus, Type 2/metabolism ; Glycopeptides/metabolism ; Tandem Mass Spectrometry ; *Periodontitis ; Biomarkers/metabolism ; Hypoglycemic Agents ; Saliva/metabolism ; }, abstract = {Periodontitis is a prevalent oral inflammatory disease that can result in tooth loss and is closely linked to type 2 diabetes (T2D). In this study, we analyzed the salivary proteome and intact N-glycopeptides (IGPs) of individuals with mild-moderate, severe, aggressive periodontitis, and periodontitis with T2D, including those treated with antidiabetic drugs, to identify specific signatures associated with the disease. Our results revealed that salivary proteins and glycoproteins were altered in all periodontitis groups (PRIDE ID: 1-20230612-72345), with fucose- and sialic acid-containing N-glycans showing the greatest increase. Additionally, differentially expressed proteins were classified into 9 clusters, including those that were increased in all periodontitis groups and those that were only altered in certain types of periodontitis. Interestingly, treatment with antidiabetic drugs reversed many of the changes observed in the salivary proteome and IGPs in T2D-related periodontitis, suggesting a potential therapeutic approach for managing periodontitis in patients with T2D. Consistent with MS/MS results, the expression of salivary IGHA2 and Fucα1-3/6GlcNAc (AAL) was significantly increased in MP. These findings provide new insights into the pathogenesis of periodontitis and highlight the potential of salivary biomarkers for diagnosis, prognosis, and monitoring of disease progression and treatment response.}, }
@article {pmid38088552, year = {2024}, author = {Konstanti, P and Ligthart, K and Fryganas, C and Constantinos, P and Smidt, H and de Vos, WM and Belzer, C}, title = {Physiology of γ-aminobutyric acid production by Akkermansia muciniphila.}, journal = {Applied and environmental microbiology}, volume = {90}, number = {1}, pages = {e0112123}, pmid = {38088552}, issn = {1098-5336}, support = {024.00.002//Soehngen Institute of Anaerobic Microbiology (SIAM)/ ; Union's Horizon 2020 grant//Eat2beNICE/ ; }, mesh = {Animals ; Humans ; *Proteomics ; *Verrucomicrobia/metabolism ; Neurotransmitter Agents/metabolism ; gamma-Aminobutyric Acid/metabolism ; Akkermansia ; }, abstract = {Gut bacteria hold the potential to produce a broad range of metabolites that can modulate human functions, including molecules with neuroactive potential. One such molecule is γ-aminobutyric acid (GABA), the main inhibitory neurotransmitter of the central nervous system in animals. Metagenomic analyses suggest that the genomes of many gut bacteria encode glutamate decarboxylase (GAD), the enzyme that catalyzes GABA production. The genome of Akkermansia muciniphila, a mucin specialist and potential next-generation probiotic from the human gut, is predicted to encode GAD, suggesting a contributing role in GABA production in the human gut. In this study, A. muciniphila was grown in batch cultures with and without pH control. In both experiments, A. muciniphila was found to produce GABA as a response to acid (pH <5.5), although only when GABA precursors, either glutamate or glutamine, were present in the medium. Proteomic analysis comparing A. muciniphila grown with and without precursors at pH 4 did not show a difference in GAD expression, suggesting that it is expressed regardless of the presence of GABA precursors. To further investigate the function of A. muciniphila GAD, we heterologously expressed the gad gene (encoded by locus tag Amuc_0372) with a His tag in Escherichia coli and purified the GAD protein. Enzyme assays showed GAD activity in a pH range between 4 and 6, with the highest specific activity at pH 5 of 144 ± 16 µM GABA/min/mg. Overall, our results demonstrate the ability of A. muciniphila to produce GABA as an acid response and unravel the conditions under which GABA production in A. muciniphila occurs.IMPORTANCEAkkermansia muciniphila is considered to be a beneficial bacterium from the human gut, but the exact mechanisms by which A. muciniphila influences its host are not yet fully understood. To this end, it is important to identify which metabolites are produced and consumed by A. muciniphila that may contribute to a healthy gut. In the present study, we demonstrate the ability of A. muciniphila to produce γ-aminobutyric acid (GABA) when grown in an acidic environment, which often occurs in the gut. GABA is the major inhibitory neurotransmitter in the central nervous system and is present in the human gut. For this reason, it is considered an important bacterial metabolite. Our finding that A. muciniphila produces GABA in acidic environments adds to the growing body of understanding of its relationship with host health and provides an explanation on how it can survive acid stress in the human gut.}, }
@article {pmid38085102, year = {2024}, author = {Blake, KS and Schwartz, DJ and Paruthiyil, S and Wang, B and Ning, J and Isidean, SD and Burns, DS and Whiteson, H and Lalani, T and Fraser, JA and Connor, P and Troth, T and Porter, CK and Tribble, DR and Riddle, MS and Gutiérrez, RL and Simons, MP and Dantas, G}, title = {Gut microbiome and antibiotic resistance effects during travelers' diarrhea treatment and prevention.}, journal = {mBio}, volume = {15}, number = {1}, pages = {e0279023}, pmid = {38085102}, issn = {2150-7511}, support = {T32 DK077653/DK/NIDDK NIH HHS/United States ; T32 DK007130/DK/NIDDK NIH HHS/United States ; 2021081/DDCF/Doris Duke Charitable Foundation/United States ; T32 GM007200/GM/NIGMS NIH HHS/United States ; R01 AI123394/AI/NIAID NIH HHS/United States ; Y01 AI005072/AI/NIAID NIH HHS/United States ; U01 AI123394/AI/NIAID NIH HHS/United States ; K08 AI159384/AI/NIAID NIH HHS/United States ; }, mesh = {Humans ; *Diarrhea/prevention &amp; control ; *Gastrointestinal Microbiome ; Travel ; Anti-Bacterial Agents/pharmacology/therapeutic use ; Drug Resistance, Microbial ; }, abstract = {The travelers' gut microbiome is potentially assaulted by acute and chronic perturbations (e.g., diarrhea, antibiotic use, and different environments). Prior studies of the impact of travel and travelers' diarrhea (TD) on the microbiome have not directly compared antibiotic regimens, and studies of different antibiotic regimens have not considered travelers' microbiomes. This gap is important to be addressed as the use of antibiotics to treat or prevent TD-even in moderate to severe cases or in regions with high infectious disease burden-is controversial based on the concerns for unintended consequences to the gut microbiome and antimicrobial resistance (AMR) emergence. Our study addresses this by evaluating the impact of defined antibiotic regimens (single-dose treatment or daily prophylaxis) on the gut microbiome and resistomes of deployed servicemembers, using samples collected during clinical trials. Our findings indicate that the antibiotic treatment regimens that were studied generally do not lead to adverse effects on the gut microbiome and resistome and identify the relative risks associated with prophylaxis. These results can be used to inform therapeutic guidelines for the prevention and treatment of TD and make progress toward using microbiome information in personalized medical care.}, }
@article {pmid38078749, year = {2024}, author = {Park, H and Joachimiak, MP and Jungbluth, SP and Yang, Z and Riehl, WJ and Canon, RS and Arkin, AP and Dehal, PS}, title = {A bacterial sensor taxonomy across earth ecosystems for machine learning applications.}, journal = {mSystems}, volume = {9}, number = {1}, pages = {e0002623}, pmid = {38078749}, issn = {2379-5077}, support = {//DOE | NNSA | LDRD | Lawrence Berkeley National Laboratory (LBNL)/ ; }, mesh = {Humans ; *Metagenomics ; *Microbiota ; Metagenome ; Machine Learning ; Earth, Planet ; }, abstract = {Microbial communities have evolved to colonize all ecosystems of the planet, from the deep sea to the human gut. Microbes survive by sensing, responding, and adapting to immediate environmental cues. This process is driven by signal transduction proteins such as histidine kinases, which use their sensing domains to bind or otherwise detect environmental cues and "transduce" signals to adjust internal processes. We hypothesized that an ecosystem's unique stimuli leave a sensor "fingerprint," able to identify and shed insight on ecosystem conditions. To test this, we collected 20,712 publicly available metagenomes from Host-associated, Environmental, and Engineered ecosystems across the globe. We extracted and clustered the collection's nearly 18M unique sensory domains into 113,712 similar groupings with MMseqs2. We built gradient-boosted decision tree machine learning models and found we could classify the ecosystem type (accuracy: 87%) and predict the levels of different physical parameters (R2 score: 83%) using the sensor cluster abundance as features. Feature importance enables identification of the most predictive sensors to differentiate between ecosystems which can lead to mechanistic interpretations if the sensor domains are well annotated. To demonstrate this, a machine learning model was trained to predict patient's disease state and used to identify domains related to oxygen sensing present in a healthy gut but missing in patients with abnormal conditions. Moreover, since 98.7% of identified sensor domains are uncharacterized, importance ranking can be used to prioritize sensors to determine what ecosystem function they may be sensing. Furthermore, these new predictive sensors can function as targets for novel sensor engineering with applications in biotechnology, ecosystem maintenance, and medicine.IMPORTANCEMicrobes infect, colonize, and proliferate due to their ability to sense and respond quickly to their surroundings. In this research, we extract the sensory proteins from a diverse range of environmental, engineered, and host-associated metagenomes. We trained machine learning classifiers using sensors as features such that it is possible to predict the ecosystem for a metagenome from its sensor profile. We use the optimized model's feature importance to identify the most impactful and predictive sensors in different environments. We next use the sensor profile from human gut metagenomes to classify their disease states and explore which sensors can explain differences between diseases. The sensors most predictive of environmental labels here, most of which correspond to uncharacterized proteins, are a useful starting point for the discovery of important environment signals and the development of possible diagnostic interventions.}, }
@article {pmid38076985, year = {2023}, author = {Jain, R and Hadjigeorgiou, A and Harkos, C and Mishra, A and Morad, G and Johnson, S and Ajami, N and Wargo, J and Munn, L and Stylianopoulos, T}, title = {Dissecting the Impact of the Gut Microbiome on Cancer Immunotherapy.}, journal = {Research square}, volume = {}, number = {}, pages = {}, pmid = {38076985}, issn = {2693-5015}, support = {F32 CA260769/CA/NCI NIH HHS/United States ; R01 NS118929/NS/NINDS NIH HHS/United States ; U01 CA224348/CA/NCI NIH HHS/United States ; R01 CA259253/CA/NCI NIH HHS/United States ; R21 EB031982/EB/NIBIB NIH HHS/United States ; R35 CA197743/CA/NCI NIH HHS/United States ; R01 CA208205/CA/NCI NIH HHS/United States ; R01 CA247441/CA/NCI NIH HHS/United States ; R01 CA219896/CA/NCI NIH HHS/United States ; U01 CA261842/CA/NCI NIH HHS/United States ; }, abstract = {The gut microbiome has emerged as a key regulator of response to cancer immunotherapy. However, there is a gap in our understanding of the underlying mechanisms by which the microbiome influences immunotherapy. To this end, we developed a mathematical model based on i) gut microbiome data derived from preclinical studies on melanomas after fecal microbiota transplant, ii) mechanistic modeling of antitumor immune response, and iii) robust association analysis of murine and human microbiome profiles with model-predicted immune profiles. Using our model, we could distill the complexity of these murine and human studies on microbiome modulation in terms of just two model parameters: the activation and killing rate constants of immune cells. We further investigated associations between specific bacterial taxonomies and antitumor immunity and immunotherapy efficacy. This model can guide the design of studies to refine and validate mechanistic links between the microbiome and immune system.}, }
@article {pmid38075911, year = {2023}, author = {Bakir-Gungor, B and Temiz, M and Jabeer, A and Wu, D and Yousef, M}, title = {microBiomeGSM: the identification of taxonomic biomarkers from metagenomic data using grouping, scoring and modeling (G-S-M) approach.}, journal = {Frontiers in microbiology}, volume = {14}, number = {}, pages = {1264941}, pmid = {38075911}, issn = {1664-302X}, abstract = {Numerous biological environments have been characterized with the advent of metagenomic sequencing using next generation sequencing which lays out the relative abundance values of microbial taxa. Modeling the human microbiome using machine learning models has the potential to identify microbial biomarkers and aid in the diagnosis of a variety of diseases such as inflammatory bowel disease, diabetes, colorectal cancer, and many others. The goal of this study is to develop an effective classification model for the analysis of metagenomic datasets associated with different diseases. In this way, we aim to identify taxonomic biomarkers associated with these diseases and facilitate disease diagnosis. The microBiomeGSM tool presented in this work incorporates the pre-existing taxonomy information into a machine learning approach and challenges to solve the classification problem in metagenomics disease-associated datasets. Based on the G-S-M (Grouping-Scoring-Modeling) approach, species level information is used as features and classified by relating their taxonomic features at different levels, including genus, family, and order. Using four different disease associated metagenomics datasets, the performance of microBiomeGSM is comparatively evaluated with other feature selection methods such as Fast Correlation Based Filter (FCBF), Select K Best (SKB), Extreme Gradient Boosting (XGB), Conditional Mutual Information Maximization (CMIM), Maximum Likelihood and Minimum Redundancy (MRMR) and Information Gain (IG), also with other classifiers such as AdaBoost, Decision Tree, LogitBoost and Random Forest. microBiomeGSM achieved the highest results with an Area under the curve (AUC) value of 0.98% at the order taxonomic level for IBDMD dataset. Another significant output of microBiomeGSM is the list of taxonomic groups that are identified as important for the disease under study and the names of the species within these groups. The association between the detected species and the disease under investigation is confirmed by previous studies in the literature. The microBiomeGSM tool and other supplementary files are publicly available at: https://github.com/malikyousef/microBiomeGSM.}, }
@article {pmid38075858, year = {2023}, author = {Marcos-Zambrano, LJ and López-Molina, VM and Bakir-Gungor, B and Frohme, M and Karaduzovic-Hadziabdic, K and Klammsteiner, T and Ibrahimi, E and Lahti, L and Loncar-Turukalo, T and Dhamo, X and Simeon, A and Nechyporenko, A and Pio, G and Przymus, P and Sampri, A and Trajkovik, V and Lacruz-Pleguezuelos, B and Aasmets, O and Araujo, R and Anagnostopoulos, I and Aydemir, &#xd6; and Berland, M and Calle, ML and Ceci, M and Duman, H and Gündoğdu, A and Havulinna, AS and Kaka Bra, KHN and Kalluci, E and Karav, S and Lode, D and Lopes, MB and May, P and Nap, B and Nedyalkova, M and Paciência, I and Pasic, L and Pujolassos, M and Shigdel, R and Susín, A and Thiele, I and Truică, CO and Wilmes, P and Yilmaz, E and Yousef, M and Claesson, MJ and Truu, J and Carrillo de Santa Pau, E}, title = {A toolbox of machine learning software to support microbiome analysis.}, journal = {Frontiers in microbiology}, volume = {14}, number = {}, pages = {1250806}, pmid = {38075858}, issn = {1664-302X}, abstract = {The human microbiome has become an area of intense research due to its potential impact on human health. However, the analysis and interpretation of this data have proven to be challenging due to its complexity and high dimensionality. Machine learning (ML) algorithms can process vast amounts of data to uncover informative patterns and relationships within the data, even with limited prior knowledge. Therefore, there has been a rapid growth in the development of software specifically designed for the analysis and interpretation of microbiome data using ML techniques. These software incorporate a wide range of ML algorithms for clustering, classification, regression, or feature selection, to identify microbial patterns and relationships within the data and generate predictive models. This rapid development with a constant need for new developments and integration of new features require efforts into compile, catalog and classify these tools to create infrastructures and services with easy, transparent, and trustable standards. Here we review the state-of-the-art for ML tools applied in human microbiome studies, performed as part of the COST Action ML4Microbiome activities. This scoping review focuses on ML based software and framework resources currently available for the analysis of microbiome data in humans. The aim is to support microbiologists and biomedical scientists to go deeper into specialized resources that integrate ML techniques and facilitate future benchmarking to create standards for the analysis of microbiome data. The software resources are organized based on the type of analysis they were developed for and the ML techniques they implement. A description of each software with examples of usage is provided including comments about pitfalls and lacks in the usage of software based on ML methods in relation to microbiome data that need to be considered by developers and users. This review represents an extensive compilation to date, offering valuable insights and guidance for researchers interested in leveraging ML approaches for microbiome analysis.}, }
@article {pmid38069593, year = {2023}, author = {Tiwari, S and Han, Z}, title = {Immunotherapy: Advancing glioblastoma treatment-A narrative review of scientific studies.}, journal = {Cancer reports (Hoboken, N.J.)}, volume = {7}, number = {2}, pages = {e1947}, pmid = {38069593}, issn = {2573-8348}, abstract = {BACKGROUND: Glioblastoma (GB) is an aggressive and deadly brain tumor with a poor prognosis despite the current standard of care, including surgery, radiation, and chemotherapy.<br><br>RECENT FINDINGS: In recent years, there has been increasing interest in the potential of immunotherapies, seen to be effective in treating other cancers, in the treatment of GB. This comprehensive review presents an in-depth analysis of the remarkable progress of immunotherapy in GB treatment, focusing on human clinical studies. It also analyzes the current findings, challenges, and limitations that underscore the transformative potential of immunotherapy in managing GB. Of particular significance, it delves into the intriguing interaction of the human microbiome with immunotherapy as a novel avenue for enhancing treatment outcomes of GB.<br><br>CONCLUSION: This study sheds light on the complex GB therapy landscape and the cutting-edge strategies that show promise for enhancing patient prognosis.}, }
@article {pmid38065982, year = {2023}, author = {Roslan, MAM and Omar, MN and Sharif, NAM and Raston, NHA and Arzmi, MH and Neoh, HM and Ramzi, AB}, title = {Recent advances in single-cell engineered live biotherapeutic products research for skin repair and disease treatment.}, journal = {NPJ biofilms and microbiomes}, volume = {9}, number = {1}, pages = {95}, pmid = {38065982}, issn = {2055-5008}, mesh = {Humans ; *Anti-Bacterial Agents ; Skin ; *Microbiota ; }, abstract = {The human microbiome has emerged as a key player in maintaining skin health, and dysbiosis has been linked to various skin disorders. Amidst growing concerns regarding the side effects of antibiotic treatments, the potential of live biotherapeutic products (LBPs) in restoring a healthy microbiome has garnered significant attention. This review aims to evaluate the current state of the art of the genetically or metabolically engineered LBPs, termed single-cell engineered LBPs (eLBPs), for skin repair and disease treatment. While some studies demonstrate promising outcomes, the translation of eLBPs into clinical applications remains a significant hurdle. Substantial concerns arise regarding the practical implementation and scalability of eLBPs, despite the evident potential they hold in targeting specific cells and delivering therapeutic agents. This review underscores the need for further research, robust clinical trials, and the exploration of current advances in eLBP-based bioengineered bacterial chassis and new outlooks to substantiate the viability and effectiveness of eLBPs as a transformative approach in skin repair and disease intervention.}, }
@article {pmid38063388, year = {2024}, author = {Song, L and Rauf, F and Hou, C-W and Qiu, J and Murugan, V and Chung, Y and Lai, H and Adam, D and Magee, DM and Trivino Soto, G and Peterson, M and Anderson, KS and Rice, SG and Readhead, B and Park, JG and LaBaer, J}, title = {Quantitative assessment of multiple pathogen exposure and immune dynamics at scale.}, journal = {Microbiology spectrum}, volume = {12}, number = {1}, pages = {e0239923}, pmid = {38063388}, issn = {2165-0497}, support = {75N91019D00024/CA/NCI NIH HHS/United States ; R21 CA196442/CA/NCI NIH HHS/United States ; }, mesh = {Humans ; Public Health ; *Immune System ; *Serology/methods ; }, abstract = {Serology reveals exposure to pathogens, as well as the state of autoimmune and other clinical conditions. It is used to evaluate individuals and their histories and as a public health tool to track epidemics. Employing a variety of formats, studies nearly always perform serology by testing response to only one or a few antigens. However, clinical outcomes of new infections also depend on which previous infections may have occurred. We developed a high-throughput serology method that evaluates responses to hundreds of antigens simultaneously. It can be used to evaluate thousands of samples at a time and provide a quantitative readout. This tool will enable doctors to monitor which pathogens an individual has been exposed to and how that changes in the future. Moreover, public health officials could track populations and look for infectious trends among large populations. Testing many potential antigens at a time may also aid in vaccine development.}, }
@article {pmid38058765, year = {2023}, author = {Ponsero, AJ and Miller, M and Hurwitz, BL}, title = {Comparison of k-mer-based de novo comparative metagenomic tools and approaches.}, journal = {Microbiome research reports}, volume = {2}, number = {4}, pages = {27}, pmid = {38058765}, issn = {2771-5965}, abstract = {Aim: Comparative metagenomic analysis requires measuring a pairwise similarity between metagenomes in the dataset. Reference-based methods that compute a beta-diversity distance between two metagenomes are highly dependent on the quality and completeness of the reference database, and their application on less studied microbiota can be challenging. On the other hand, de-novo comparative metagenomic methods only rely on the sequence composition of metagenomes to compare datasets. While each one of these approaches has its strengths and limitations, their comparison is currently limited. Methods: We developed sets of simulated short-reads metagenomes to (1) compare k-mer-based and taxonomy-based distances and evaluate the impact of technical and biological variables on these metrics and (2) evaluate the effect of k-mer sketching and filtering. We used a real-world metagenomic dataset to provide an overview of the currently available tools for de novo metagenomic comparative analysis. Results: Using simulated metagenomes of known composition and controlled error rate, we showed that k-mer-based distance metrics were well correlated to the taxonomic distance metric for quantitative Beta-diversity metrics, but the correlation was low for presence/absence distances. The community complexity in terms of taxa richness and the sequencing depth significantly affected the quality of the k-mer-based distances, while the impact of low amounts of sequence contamination and sequencing error was limited. Finally, we benchmarked currently available de-novo comparative metagenomic tools and compared their output on two datasets of fecal metagenomes and showed that most k-mer-based tools were able to recapitulate the data structure observed using taxonomic approaches. Conclusion: This study expands our understanding of the strength and limitations of k-mer-based de novo comparative metagenomic approaches and aims to provide concrete guidelines for researchers interested in applying these approaches to their metagenomic datasets.}, }
@article {pmid38053859, year = {2023}, author = {Sharma, S and Bakht, A and Jahanzaib, M and Kim, M and Lee, H and Park, C and Park, D}, title = {Characterization of bacterial species and antibiotic resistance observed in Seoul, South Korea's popular Gangnam-gu area.}, journal = {Heliyon}, volume = {9}, number = {11}, pages = {e21751}, pmid = {38053859}, issn = {2405-8440}, abstract = {Public transportation facilities, especially road crossings, which raise the pathogenic potential of urban environments, are the most conducive places for the transfer of germs between people and the environment. It is necessary to study the variety of the microbiome and describe its unique characteristics to comprehend these relationships. In this investigation, we used 16 S rRNA gene sample sequencing to examine the biological constituents and inhalable, thoracic, and alveolar particles in aerosol samples collected from busy areas in the Gangnam-gu district of the Seoul metropolitan area using a mobile vehicle. We also conducted a comparison analysis of these findings with the previously published data and tested for antibiotic resistance to determine the distribution of bacteria related to the human microbiome and the environment. Actinobacteria, Cyanobacteria, Bacteriodetes, Proteobacteria, and Firmicutes were the top five phyla in the bacterial 16 S rRNA libraries, accounting for >90 % of all readings across all examined locations. The most prevalent classes among the 12 found bacterial classes were Bacilli (45.812 %), Gammaproteobacteria (25.238 %), Tissierellia (13.078 %), Clostridia (5.697 %), and Alphaproteobacteria (5.142 %). The data acquired offer useful information on the variety of bacterial communities and their resistance to antibiotic drugs on the streets of Gangnam-gu, one of the most significant social centers in the Seoul metropolitan area. This work emphasizes the relevance of biological particles and particulate matter in the air, and it suggests more research is needed to perform biological characterization of the ambient particulate matter.}, }
@article {pmid38051964, year = {2023}, author = {Lavoie, T and Appaneal, HJ and LaPlante, KL}, title = {Advancements in Novel Live Biotherapeutic Products for Clostridioides difficile Infection Prevention.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {77}, number = {Suppl 6}, pages = {S447-S454}, doi = {10.1093/cid/ciad639}, pmid = {38051964}, issn = {1537-6591}, support = {//Seres and Ferring/ ; }, mesh = {Humans ; Dysbiosis/therapy ; *Clostridioides difficile ; Fecal Microbiota Transplantation ; *Clostridium Infections/prevention &amp; control/drug therapy ; Feces/microbiology ; Anti-Bacterial Agents/therapeutic use ; }, abstract = {The profound impact of the human microbiome on health and disease has captivated the interest of clinical and scientific communities. The human body hosts a vast array of microorganisms collectively forming the human microbiome, which significantly influences various physiological processes and profoundly shapes overall well-being. Notably, the gut stands out as an exceptional reservoir, harboring the most significant concentration of microorganisms, akin to an organ in itself. The gut microbiome's composition and function are influenced by genetics, environment, age, underlying conditions, and antibiotic usage, leading to dysbiosis and pathogenesis, such as Clostridioides difficile infection (CDI). Conventional CDI treatment, involving antibiotics like oral vancomycin and fidaxomicin, fails to address dysbiosis and may further disrupt gut microbial communities. Consequently, emerging therapeutic strategies are focused on targeting dysbiosis and restoring gut microbiota to advance CDI therapeutics. Fecal microbiota transplantation (FMT) has demonstrated remarkable efficacy in treating recurrent CDI by transferring processed stool from a healthy donor to a recipient, restoring gut dysbiosis and enhancing bacterial diversity. Moreover, 2 newer Food and Drug Administration (FDA)-approved live biotherapeutic products (LBP), namely, Fecal Microbiota Live-JSLM and Fecal Microbiota Spores Live-BRPK, have shown promise in preventing CDI recurrence. This review explores the role of the gut microbiota in preventing and treating CDI, with an emphasis on gut-based interventions like FMT and fecal microbiota-based products that hold potential for gut restoration and prevention of CDI recurrence. Understanding the microbiome's impact on CDI prevention and treatment offers valuable insights for advancing future CDI therapeutics.}, }
@article {pmid38049273, year = {2024}, author = {Mantegazza, G and Duncan, R and Telesca, N and Gargari, G and Perotti, S and Riso, P and Guglielmetti, S}, title = {Lactic acid bacteria naturally associated with ready-to-eat rocket salad can survive the human gastrointestinal transit.}, journal = {Food microbiology}, volume = {118}, number = {}, pages = {104418}, doi = {10.1016/j.fm.2023.104418}, pmid = {38049273}, issn = {1095-9998}, mesh = {Humans ; *Lactobacillales ; *Salads ; Food Microbiology ; Gastrointestinal Transit ; Vegetables/microbiology ; Bacteria ; Leuconostoc ; }, abstract = {It was theorized that modernization and the decline in harmless microbial populations associated with food have altered the gut microbiota, impacting host metabolism and immunity. Western dietary patterns, characterized by processed foods and preservation methods, may significantly reduce the microbial population associated with food. To mitigate the consequences of bacterial deprivation, the integration of these diets with fermented foods is commonly proposed. Nonetheless, non-fermented food consumed raw may also be an important source of viable microbial cells for the human microbiome. This study investigates whether salad-associated LAB can survive the gastrointestinal transit (GIT) and contribute to the gut microbiota. LAB strains were quantified and isolated from rocket salad (Eruca vesicaria subsp. sativa), and their survival through GIT was assessed via intervention trials in healthy adults and in vitro. Moreover, bacterial communities in fecal samples were analyzed after three days of rocket salad consumption. Washing with a sodium hypochlorite solution drastically reduced total bacterial load and eliminated viable LAB. The quantity of LAB introduced through salads did not significantly alter the gut microbiota composition. Rocket salads harbored Weissella and Leuconostoc species. A significant increase in Weissella spp. but not in Leuconostoc spp. was observed after the consumption of rocket salad. Simulated GIT experiments suggested that the food matrix and the initial number of ingested viable bacteria may have been important in determining survival. These findings propose that plant products could serve as sources of live LAB for the human gut. Further research with diverse vegetables and longer interventions is needed, encouraging studies on raw, non-fermented foods and their impact on the human intestinal microbiome.}, }
@article {pmid38048079, year = {2023}, author = {Fu, P and Wu, Y and Zhang, Z and Qiu, Y and Wang, Y and Peng, Y}, title = {VIGA: a one-stop tool for eukaryotic virus identification and genome assembly from next-generation-sequencing data.}, journal = {Briefings in bioinformatics}, volume = {25}, number = {1}, pages = {}, pmid = {38048079}, issn = {1477-4054}, support = {32370700//National Natural Science Foundation of China/ ; 2022YFC2303802//National Key Plan for Scientific Research and Development of China/ ; }, mesh = {Humans ; High-Throughput Nucleotide Sequencing ; *Colitis, Ulcerative ; *Crohn Disease ; Genome, Viral ; Metagenome ; }, abstract = {Identification of viruses and further assembly of viral genomes from the next-generation-sequencing data are essential steps in virome studies. This study presented a one-stop tool named VIGA (available at https://github.com/viralInformatics/VIGA) for eukaryotic virus identification and genome assembly from NGS data. It was composed of four modules, namely, identification, taxonomic annotation, assembly and novel virus discovery, which integrated several third-party tools such as BLAST, Trinity, MetaCompass and RagTag. Evaluation on multiple simulated and real virome datasets showed that VIGA assembled more complete virus genomes than its competitors on both the metatranscriptomic and metagenomic data and performed well in assembling virus genomes at the strain level. Finally, VIGA was used to investigate the virome in metatranscriptomic data from the Human Microbiome Project and revealed different composition and positive rate of viromes in diseases of prediabetes, Crohn's disease and ulcerative colitis. Overall, VIGA would help much in identification and characterization of viromes, especially the known viruses, in future studies.}, }
@article {pmid38047279, year = {2023}, author = {Candeliere, F and Musmeci, E and Amaretti, A and Sola, L and Raimondi, S and Rossi, M}, title = {Profiling of the intestinal community of Clostridia: taxonomy and evolutionary analysis.}, journal = {Microbiome research reports}, volume = {2}, number = {2}, pages = {13}, pmid = {38047279}, issn = {2771-5965}, abstract = {Aim: Clostridia are relevant commensals of the human gut due to their major presence and correlations to the host. In this study, we investigated intestinal Clostridia of 51 healthy subjects and reconstructed their taxonomy and phylogeny. The relatively small number of intestinal Clostridia allowed a systematic whole genome approach based on average amino acid identity (AAI) and core genome with the aim of revising the current classification into genera and determining evolutionary relationships. Methods: 51 healthy subjects' metagenomes were retrieved from public databases. After the dataset's validation through comparison with Human Microbiome Project (HMP) samples, the metagenomes were profiled using MetaPhlAn3 to identify the population ascribed to the class Clostridia. Intestinal Clostridia genomes were retrieved and subjected to AAI analysis and core genome identification. Phylogeny investigation was conducted with RAxML and Unweighted Pair Group Method with Arithmetic Mean (UPGMA) algorithms, and SplitsTree for split decomposition. Results: 225 out of 406 bacterial taxonomic units were ascribed to Bacillota [Firmicutes], among which 124 were assigned to the class Clostridia. 77 out of the 124 taxonomic units were referred to a species, altogether covering 87.7% of Clostridia abundance. According to the lowest AAI genus boundary set at 55%, 15 putative genera encompassing more than one species (G1 to G15) were identified, while 19 species did not cluster with any other one and each appeared to belong to a diverse genus. Phylogenetic investigations highlighted that most of the species clustered into three main evolutive clades. Conclusion: This study shed light on the species of Clostridia colonizing the gut of healthy adults and pinpointed several gaps in knowledge regarding the taxonomy and the phylogeny of Clostridia.}, }
@article {pmid38045923, year = {2023}, author = {Al, KF and Allen, L and Bedell, S and Burton, JP and de Vrijer, B}, title = {Assessing the impact of pregnancy and birth factors on the maternal and infant microbiota.}, journal = {Microbiome research reports}, volume = {2}, number = {4}, pages = {29}, pmid = {38045923}, issn = {2771-5965}, abstract = {Background: The microbiota acquired at birth is known to play an intimate role in later life health and disease and has been shown to be affected by the mode of birth. There has been recent interest in microbiota correction by maternal vaginal seeding in Cesarean section-born infants; however, the safety of this practice has been debated. The aim of this study was to assess how other factors, such as timing of sampling, maternal obesity, vaginal Group B Streptococcus colonization (GBS), and antibiotic exposure, affect the maternal and infant microbiota. Methods: Maternal vaginal and saliva samples were collected at three time periods: 35-37 weeks gestation (prenatal), within 24-36 hours after birth (birth), and at ~6 weeks postpartum. Infant saliva and stool samples were collected at ~6 weeks postpartum. 16S rRNA amplicon sequencing was utilized to assess the taxonomic and inferred functional compositions of the bacterial communities from both mothers and infants. Results: Samples from 36 mothers and 32 infants were obtained. Gestational age, breastfeeding, mode of birth, and gravidity were associated with taxonomic alterations in the infant samples, while obesity, antibiotic use, and GBS status were not. Maternal samples were predominantly affected by time, whereby significant alterations including increased microbial diversity were seen at birth and persisted to 6 weeks postpartum. Conclusion: This study provides information on the relationship between health and delivery factors and changes in vaginal and infant microbiota. These results may better direct clinicians and mothers in optimizing the infant microbiota towards health during infancy and later life.}, }
@article {pmid38045612, year = {2023}, author = {Brüssow, H}, title = {The human microbiome project at ten years - some critical comments and reflections on "our third genome", the human virome.}, journal = {Microbiome research reports}, volume = {2}, number = {1}, pages = {7}, pmid = {38045612}, issn = {2771-5965}, abstract = {The Human Microbiome Project (HMP) has raised great expectations claiming the far-reaching influence of the microbiome on human health and disease ranging from obesity and malnutrition to effects going well beyond the gut. So far, with the notable exception of fecal microbiota transplantation in Clostridioides difficile infection, practical application of microbiome intervention has only achieved modest clinical effects. It is argued here that we need criteria for the link between microbiome and disease modelled on the links between pathogens and infectious disease in Koch's postulates. The most important question is whether the microbiome change is a cause of the given disease or a consequence of a pathology leading to disease where the microbiome change is only a parallel event without a causal connection to the disease - in philosophical parlance, an epiphenomenon. Also discussed here is whether human virome research is a necessary complement to the microbiome project with a high potential for practical applications.}, }
@article {pmid38045610, year = {2023}, author = {Reid, G}, title = {Perspective: microbial interventions in the urinary tract.}, journal = {Microbiome research reports}, volume = {2}, number = {1}, pages = {3}, pmid = {38045610}, issn = {2771-5965}, abstract = {Despite multiple advances in medicine, the management of urinary tract infections (UTIs) in women has remained stalled for decades. To prevent the development of symptomatic recurrences, low-dose antibiotics are the mainstay, while alternative approaches have been attempted with limited success. The use of probiotics was first considered forty years ago, and while some promising studies have been published, additional evidence in larger patient groups is needed to recommend specific strains as a primary preventive regimen. Overall, the role of beneficial microbes in reducing the risk of UTI and other urological diseases, such as urolithiasis, remains a target for researchers. The aim of this perspective is to offer a viewpoint on the status of this approach and recommendations for how to develop novel probiotic therapies.}, }
@article {pmid38045608, year = {2023}, author = {Segers, A and de Vos, WM}, title = {Mode of action of Akkermansia muciniphila in the intestinal dialogue: role of extracellular proteins, metabolites and cell envelope components.}, journal = {Microbiome research reports}, volume = {2}, number = {1}, pages = {6}, pmid = {38045608}, issn = {2771-5965}, abstract = {Akkermansia muciniphila is a promising next-generation beneficial microbe due to its natural presence in the mucus layer of the gut, its symbiotic ability to degrade mucus, and its capacity to improve the intestinal barrier function. A. muciniphila is able to counteract weight gain and immuno-metabolic disturbances in several animal models. Many of these disorders, including obesity and auto-immune diseases, have been associated with decreased gut barrier function and consequent increased inflammation. Since A. muciniphila was found to normalize these changes and strengthen the gut barrier function, it is hypothesized that other beneficial effects of A. muciniphila might be caused by this restoration. In search for A. muciniphila's mode of action in enhancing the gut barrier function and promoting health, we reasoned that secreted components or cell envelope components of A. muciniphila are interesting candidates as they can potentially reach and interact with the epithelial barrier. In this review, we focus on the potential mechanisms through which A. muciniphila can exert its beneficial effects on the host by the production of extracellular and secreted proteins, metabolites and cell envelope components. These products have been studied in isolation for their structure, signaling capacity, and in some cases, also for their effects in preclinical models. This includes the protein known as Amuc_1100, which we here rename as pilus-associated signaling (PAS) protein , the P9 protein encoded by Amuc_1631, the short-chain fatty acids acetate and propionate, and cell envelope components, such as phosphatidylethanolamine and peptidoglycan.}, }
@article {pmid38045399, year = {2023}, author = {Olm, MR and Spencer, SP and Silva, EL and Sonnenburg, JL}, title = {Metagenomic Immunoglobulin Sequencing (MIG-Seq) Exposes Patterns of IgA Antibody Binding in the Healthy Human Gut Microbiome.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {38045399}, issn = {2692-8205}, support = {DP1 AT009892/AT/NCCIH NIH HHS/United States ; R01 DK085025/DK/NIDDK NIH HHS/United States ; T32 DK007056/DK/NIDDK NIH HHS/United States ; T32 AI007328/AI/NIAID NIH HHS/United States ; K08 DK134856/DK/NIDDK NIH HHS/United States ; S10 OD026929/OD/NIH HHS/United States ; S10 OD026831/OD/NIH HHS/United States ; F32 DK128865/DK/NIDDK NIH HHS/United States ; }, abstract = {IgA, the most highly produced human antibody, is continually secreted into the gut to shape the intestinal microbiota. Methodological limitations have critically hindered defining which microbial strains are targeted by IgA and why. Here, we develop a new technique, Metagenomic Immunoglobulin Sequencing (MIG-Seq), and use it to determine IgA coating levels for thousands of gut microbiome strains in healthy humans. We find that microbes associated with both health and disease have higher levels of coating, and that microbial genes are highly predictive of IgA binding levels, with mucus degradation genes especially correlated with high binding. We find a significant reduction in replication rates among microbes bound by IgA, and demonstrate that IgA binding is more correlated with host immune status than traditional microbial abundance measures. This study introduces a powerful technique for assessing strain-level IgA binding in human stool, paving the way for deeper understanding of IgA-based host microbe interactions.}, }
@article {pmid38041504, year = {2023}, author = {Fujimoto, A and Fujii, K and Suido, H and Fukuike, H and Miyake, N and Suzuki, H and Eguchi, T and Tobata, H}, title = {Changes in oral microflora following 0.3% cetylpyridinium chloride-containing mouth spray intervention in adult volunteers after professional oral care: Randomized clinical study.}, journal = {Clinical and experimental dental research}, volume = {9}, number = {6}, pages = {1034-1043}, pmid = {38041504}, issn = {2057-4347}, support = {//Sunstar Inc./ ; }, mesh = {Adult ; Humans ; Cetylpyridinium ; *Anti-Infective Agents, Local ; Mouthwashes ; *Dental Plaque/microbiology ; Tongue/microbiology ; Double-Blind Method ; Volunteers ; }, abstract = {OBJECTIVES: This study explored the changes in bacterial flora composition and total bacterial count in the saliva and tongue coating, along with the change in the tongue coating index (TCI) following an intervention with 0.3% cetylpyridinium chloride (CPC) mouth spray after professional oral care.<br><br>MATERIALS AND METHODS: Fifty-two adult volunteers aged 30-60 years were equally divided into CPC spray (n&#x2009;=&#x2009;26) and control (n&#x2009;=&#x2009;26) groups. All subjects underwent scaling and polishing. The CPC spray group was administered four puffs of CPC spray to the tongue dorsum four times a day for 3 weeks. The control group performed only routine daily oral care (brushing) and did not use any other spray. Bacteriological evaluation of saliva and tongue coating was performed using 16S ribosomal RNA&#xa0;gene sequencing and quantitative polymerase chain reaction. The tongue coating was evaluated to calculate the TCI. A per-protocol analysis was conducted for 44 subjects (CPC spray group, n&#x2009;=&#x2009;23; control group, n&#x2009;=&#x2009;21).<br><br>RESULTS: At 1 and 3 weeks after CPC spray use, the flora of the saliva and tongue coating changed; the genus Haemophilus was dominant in the CPC spray group, whereas the genus Saccharibacteria was dominant in the control group. The sampling time differed among individual participants, which may have affected the bacterial counts. There was no significant intragroup change in TCI in either group.<br><br>CONCLUSIONS: CPC spray affected the bacterial flora in the saliva and tongue coating, particularly with respect to an increase in the abundance of Haemophilus. However, CPC spray did not change the TCI. These results suggest that it may be optimal to combine CPC spray with a physical cleaning method such as using a tongue brush or scraper.&#xa0;Clinical Trial Registration:&#xa0;University Hospital Medical Information Network UMIN000041140.}, }
@article {pmid38032644, year = {2023}, author = {Landry, MJ and Ward, CP and Cunanan, KM and Durand, LR and Perelman, D and Robinson, JL and Hennings, T and Koh, L and Dant, C and Zeitlin, A and Ebel, ER and Sonnenburg, ED and Sonnenburg, JL and Gardner, CD}, title = {Cardiometabolic Effects of Omnivorous vs Vegan Diets in Identical Twins: A Randomized Clinical Trial.}, journal = {JAMA network open}, volume = {6}, number = {11}, pages = {e2344457}, pmid = {38032644}, issn = {2574-3805}, support = {UL1 TR003142/TR/NCATS NIH HHS/United States ; UL1 TR001085/TR/NCATS NIH HHS/United States ; T32 HL161270/HL/NHLBI NIH HHS/United States ; }, mesh = {Adult ; Female ; Humans ; Male ; Body Weight ; *Cardiovascular Diseases/prevention &amp; control ; Cholesterol, LDL ; *Diet, Vegan ; Insulins ; Twins, Monozygotic ; Vegetables ; Middle Aged ; Diet, Healthy ; }, abstract = {IMPORTANCE: Increasing evidence suggests that, compared with an omnivorous diet, a vegan diet confers potential cardiovascular benefits from improved diet quality (ie, higher consumption of vegetables, legumes, fruits, whole grains, nuts, and seeds).<br><br>OBJECTIVE: To compare the effects of a healthy vegan vs healthy omnivorous diet on cardiometabolic measures during an 8-week intervention.<br><br>This single-center, population-based randomized clinical trial of 22 pairs of twins (N&#x2009;=&#x2009;44) randomized participants to a vegan or omnivorous diet (1 twin per diet). Participant enrollment began March 28, 2022, and continued through May 5, 2022. The date of final follow-up data collection was July 20, 2022. This 8-week, open-label, parallel, dietary randomized clinical trial compared the health impact of a vegan diet vs an omnivorous diet in identical twins. Primary analysis included all available data.<br><br>INTERVENTION: Twin pairs were randomized to follow a healthy vegan diet or a healthy omnivorous diet for 8 weeks. Diet-specific meals were provided via a meal delivery service from baseline through week 4, and from weeks 5 to 8 participants prepared their own diet-appropriate meals and snacks.<br><br>MAIN OUTCOMES AND MEASURES: The primary outcome was difference in low-density lipoprotein cholesterol concentration from baseline to end point (week 8). Secondary outcome measures were changes in cardiometabolic factors (plasma lipids, glucose, and insulin levels and serum trimethylamine N-oxide level), plasma vitamin B12 level, and body weight. Exploratory measures were adherence to study diets, ease or difficulty in following the diets, participant energy levels, and sense of well-being.<br><br>RESULTS: A total of 22 pairs (N&#x2009;=&#x2009;44) of twins (34 [77.3%] female; mean [SD] age, 39.6 [12.7] years; mean [SD] body mass index, 25.9 [4.7]) were enrolled in the study. After 8 weeks, compared with twins randomized to an omnivorous diet, the twins randomized to the vegan diet experienced significant mean (SD) decreases in low-density lipoprotein cholesterol concentration (-13.9 [5.8] mg/dL; 95% CI, -25.3 to -2.4 mg/dL), fasting insulin level (-2.9 [1.3] &#x3bc;IU/mL; 95% CI, -5.3 to -0.4 &#x3bc;IU/mL), and body weight (-1.9 [0.7] kg; 95% CI, -3.3 to -0.6 kg).<br><br>CONCLUSIONS AND RELEVANCE: In this randomized clinical trial of the cardiometabolic effects of omnivorous vs vegan diets in identical twins, the healthy vegan diet led to improved cardiometabolic outcomes compared with a healthy omnivorous diet. Clinicians can consider this dietary approach as a healthy alternative for their patients.<br><br>TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05297825.}, }
@article {pmid38029237, year = {2023}, author = {Rinaldi, F and Chirico, R and Trink, A and Pinto, D}, title = {Resistance and Pseudo-resistance to permethrin: the importance of controlling scabies.}, journal = {Frontiers in cellular and infection microbiology}, volume = {13}, number = {}, pages = {1297337}, pmid = {38029237}, issn = {2235-2988}, mesh = {Humans ; *Scabies/drug therapy ; Permethrin/pharmacology ; *Insecticides/pharmacology ; Ivermectin ; }, }
@article {pmid38022690, year = {2023}, author = {Meng, D and Ai, S and Spanos, M and Shi, X and Li, G and Cretoiu, D and Zhou, Q and Xiao, J}, title = {Exercise and microbiome: From big data to therapy.}, journal = {Computational and structural biotechnology journal}, volume = {21}, number = {}, pages = {5434-5445}, pmid = {38022690}, issn = {2001-0370}, abstract = {Exercise is a vital component in maintaining optimal health and serves as a prospective therapeutic intervention for various diseases. The human microbiome, comprised of trillions of microorganisms, plays a crucial role in overall health. Given the advancements in microbiome research, substantial databases have been created to decipher the functionality and mechanisms of the microbiome in health and disease contexts. This review presents an initial overview of microbiomics development and related databases, followed by an in-depth description of the multi-omics technologies for microbiome. It subsequently synthesizes the research pertaining to exercise-induced modifications of the microbiome and diseases that impact the microbiome. Finally, it highlights the potential therapeutic implications of an exercise-modulated microbiome in intestinal disease, obesity and diabetes, cardiovascular disease, and immune/inflammation-related diseases.}, }
@article {pmid38022043, year = {2023}, author = {Kaliamoorthy, S and Priya Sayeeram, S and SundarRaj, S and Balakrishnan, J and Nagarajan, M and Samidorai, A}, title = {Investigating the Association Between Fusobacterium nucleatum and Oral Squamous Cell Carcinoma: A Pilot Case-Control Study on Tissue Samples.}, journal = {Cureus}, volume = {15}, number = {10}, pages = {e47238}, pmid = {38022043}, issn = {2168-8184}, abstract = {Background Fusobacterium nucleatum (F. nucleatum) has been increasingly linked to oral squamous cell carcinoma (OSCC), prompting this study to explore its presence using polymerase chain reaction (PCR) and evaluate its clinical significance. Methods In this pilot case-control study, 12 OSCC tissue samples and 12 non-cancerous oral mucosal tissue samples were analyzed. Total RNA extraction and complementary DNA (cDNA) synthesis were performed using Trizol-based methods, followed by PCR amplification and gel electrophoresis. The clinical characteristics of participants and PCR results were recorded. Results Among the OSCC tissue samples, three out of 12 tested positive for F. nucleatum, while none of the control samples showed its presence. The detection rate of F. nucleatum in OSCC was 25%. Gel analysis confirmed specific amplicon amplification, and ImageJ software enabled copy number quantification. Discussion Our findings support previous research indicating a potential association between F. nucleatum and OSCC. Understanding the etiological significance of F. nucleatum in OSCC has clinical implications, including early detection, risk stratification, and prognostication. However, the limited sample size and the need for further research to elucidate underlying mechanisms are acknowledged. Conclusion This pilot study provides initial evidence of F. nucleatum's presence in a subset of OSCC samples, supporting its potential association with oral cancer. Detecting F. nucleatum in OSCC tissues holds promise for future research and clinical applications as a diagnostic and prognostic biomarker. Understanding its role in oral carcinogenesis will facilitate the development of targeted therapeutic strategies. Larger studies are warranted to validate these findings and investigate the precise mechanisms involved.}, }
@article {pmid38018964, year = {2024}, author = {Nguyen, VH and Sharon, BM and Shipman, BM and Zimmern, PE and De Nisco, NJ}, title = {Complete genomes of Limosilactobacillus portuensis and Limosilactobacillus vaginalis isolated from the urine of postmenopausal women.}, journal = {Microbiology resource announcements}, volume = {13}, number = {1}, pages = {e0088323}, pmid = {38018964}, issn = {2576-098X}, support = {R01 DK131267/DK/NIDDK NIH HHS/United States ; }, abstract = {There is frequent evidence that Limosilactobacillus vaginalis colonizes female genitourinary tracts but few reports of Limosilactobacillus portuensis. Their role in urinary tract infection (UTI) is unclear. We present the first complete genome of L. portuensis and a complete genome of L. vaginalis isolated from postmenopausal women with varying UTI histories.}, }
@article {pmid38011708, year = {2023}, author = {Moody, M and Sawyer, R}, title = {Is There a Community Microbial Community? A Comparison of Pathogens Between Two Hospital Surgical Intensive Care Units in a Single City.}, journal = {Surgical infections}, volume = {24}, number = {10}, pages = {897-902}, doi = {10.1089/sur.2023.069}, pmid = {38011708}, issn = {1557-8674}, mesh = {Humans ; *Intensive Care Units ; Bacteria ; *Cross Infection/epidemiology/microbiology ; Hospitals ; Critical Care ; }, abstract = {Background: Nosocomial and health-care-associated infections drive increased healthcare costs and negatively affect patient outcomes. The human microbiome has been heavily explored in recent years with incomplete data regarding hospital-specific and community-specific microbial communities. Although bacterial species differ between intensive care units in the same hospital, it is unclear if they differ between similar units in similar hospitals in the same community. Our hypothesis is that pathogens in surgical intensive care units (SICUs) are distinct between hospitals, even in the same community. Methods: From 2017 to 2021, data were collected prospectively from the SICUs of two 400-bed hospitals located three miles apart in the same city (Hospital A and Hospital B). Infections defined using U.S. Centers for Disease Control and Prevention (CDC) criteria were recorded for trauma and general surgery patients, as well as patient demographics, Acute Physiology and Chronic Health Evaluation (APACHE) II score, and causative organism. Results: Overall, Escherichia coli was the most commonly isolated pathogen in Hospital A, whereas Staphylococcus aureus was most commonly isolated at Hospital B. Enterococci were more common in Hospital A, and Haemophilus influenzae and Enterobacter spp. were more common in Hospital B. After stratification between trauma and non-trauma patients, however, these differences disappeared, with the exception of more overall gram-positive organisms and fewer gram-negative organisms among Hospital A trauma patients compared to Hospital B. There were no differences in rates of isolation of either fungi or resistant bacteria between hospitals. Conclusions: At a species level, admission diagnosis appears to be a greater determinant of pathogen isolation than hospital when comparing similar intensive care units (ICUs) in the same geographic area, but a larger body of data is needed to flesh out a distinct microbial map of the organisms occupying a certain geographic region. Further areas for investigation include comparison between hospital units, specific anatomic sites, and ICU versus floor patients.}, }
@article {pmid38007438, year = {2023}, author = {Al, KF and Joris, BR and Daisley, BA and Chmiel, JA and Bjazevic, J and Reid, G and Gloor, GB and Denstedt, JD and Razvi, H and Burton, JP}, title = {Multi-site microbiota alteration is a hallmark of kidney stone formation.}, journal = {Microbiome}, volume = {11}, number = {1}, pages = {263}, pmid = {38007438}, issn = {2049-2618}, mesh = {Humans ; *Kidney Calculi ; *Microbiota/genetics ; Oxalates/metabolism ; Metagenome ; Bacteria ; }, abstract = {BACKGROUND: Inquiry of microbiota involvement in kidney stone disease (KSD) has largely focussed on potential oxalate handling abilities by gut bacteria and the increased association with antibiotic exposure. By systematically comparing the gut, urinary, and oral microbiota of 83 stone formers (SF) and 30 healthy controls (HC), we provide a unified assessment of the bacterial contribution to KSD.<br><br>RESULTS: Amplicon and shotgun metagenomic sequencing approaches were consistent in identifying multi-site microbiota disturbances in SF relative to HC. Biomarker taxa, reduced taxonomic and functional diversity, functional replacement of core bioenergetic pathways with virulence-associated gene markers, and community network collapse defined SF, but differences between cohorts did not extend to oxalate metabolism.<br><br>CONCLUSIONS: We conclude that multi-site microbiota alteration is a hallmark of SF, and KSD treatment should consider microbial functional restoration and the avoidance of aberrant modulators such as poor diet and antibiotics where applicable to prevent stone recurrence. Video Abstract.}, }
@article {pmid38006744, year = {2023}, author = {Elgart, M and Zhang, Y and Zhang, Y and Yu, B and Kim, Y and Zee, PC and Gellman, MD and Boerwinkle, E and Daviglus, ML and Cai, J and Redline, S and Burk, RD and Kaplan, R and Sofer, T}, title = {Anaerobic pathogens associated with OSA may contribute to pathophysiology via amino-acid depletion.}, journal = {EBioMedicine}, volume = {98}, number = {}, pages = {104891}, pmid = {38006744}, issn = {2352-3964}, support = {HHSN268201300004C/HL/NHLBI NIH HHS/United States ; R21 HL145425/HL/NHLBI NIH HHS/United States ; N01HC65236/HL/NHLBI NIH HHS/United States ; N01HC65235/HL/NHLBI NIH HHS/United States ; R01 HL161012/HL/NHLBI NIH HHS/United States ; R35 HL135818/HL/NHLBI NIH HHS/United States ; N01HC65233/HL/NHLBI NIH HHS/United States ; N01HC65237/HL/NHLBI NIH HHS/United States ; HHSN268201300003C/HL/NHLBI NIH HHS/United States ; }, mesh = {Humans ; *Amino Acids ; Anaerobiosis ; Cohort Studies ; Prospective Studies ; *Sleep Apnea, Obstructive/complications ; }, abstract = {BACKGROUND: The human microbiome is linked to multiple metabolic disorders such as obesity and diabetes. Obstructive sleep apnoea (OSA) is a common sleep disorder with several metabolic risk factors. We investigated the associations between the gut microbiome composition and function, and measures of OSA severity in participants from a prospective community-based cohort study: the Hispanic Community Health Study/Study of Latinos (HCHS/SOL).<br><br>METHODS: Bacterial-Wide Association Analysis (BWAS) of gut microbiome measured via metagenomics with OSA measures was performed adjusting for clinical, lifestyle and co-morbidities. This was followed by functional analysis of the OSA-enriched bacteria. We utilized additional metabolomic and transcriptomic associations to suggest possible mechanisms explaining the microbiome effects on OSA.<br><br>FINDINGS: Several uncommon anaerobic human pathogens were associated with OSA severity. These belong to the Lachnospira, Actinomyces, Kingella and Eubacterium genera. Functional analysis revealed enrichment in 49 processes including many anaerobic-related ones. Severe OSA was associated with the depletion of the amino acids glycine and glutamine in the blood, yet neither diet nor gene expression revealed any changes in the production or consumption of these amino acids.<br><br>INTERPRETATION: We show anaerobic bacterial communities to be a novel component of OSA pathophysiology. These are established in the oxygen-poor environments characteristic of OSA. We hypothesize that these bacteria deplete certain amino acids required for normal human homeostasis and muscle tone, contributing to OSA phenotypes. Future work should test this hypothesis as well as consider diagnostics via anaerobic bacteria detection and possible interventions via antibiotics and amino-acid supplementation.<br><br>FUNDING: Described in methods.}, }
@article {pmid38004827, year = {2023}, author = {Kim, J and Koh, H}, title = {MiTree: A Unified Web Cloud Analytic Platform for User-Friendly and Interpretable Microbiome Data Mining Using Tree-Based Methods.}, journal = {Microorganisms}, volume = {11}, number = {11}, pages = {}, pmid = {38004827}, issn = {2076-2607}, support = {2021R1C1C1013861//National Research Foundation of Korea/ ; }, abstract = {The advent of next-generation sequencing has greatly accelerated the field of human microbiome studies. Currently, investigators are seeking, struggling and competing to find new ways to diagnose, treat and prevent human diseases through the human microbiome. Machine learning is a promising approach to help such an effort, especially due to the high complexity of microbiome data. However, many of the current machine learning algorithms are in a "black box", i.e., they are difficult to understand and interpret. In addition, clinicians, public health practitioners and biologists are not usually skilled at computer programming, and they do not always have high-end computing devices. Thus, in this study, we introduce a unified web cloud analytic platform, named MiTree, for user-friendly and interpretable microbiome data mining. MiTree employs tree-based learning methods, including decision tree, random forest and gradient boosting, that are well understood and suited to human microbiome studies. We also stress that MiTree can address both classification and regression problems through covariate-adjusted or unadjusted analysis. MiTree should serve as an easy-to-use and interpretable data mining tool for microbiome-based disease prediction modeling, and should provide new insights into microbiome-based diagnostics, treatment and prevention. MiTree is an open-source software that is available on our web server.}, }
@article {pmid38003692, year = {2023}, author = {Maslennikov, R and Poluektova, E and Zolnikova, O and Sedova, A and Kurbatova, A and Shulpekova, Y and Dzhakhaya, N and Kardasheva, S and Nadinskaia, M and Bueverova, E and Nechaev, V and Karchevskaya, A and Ivashkin, V}, title = {Gut Microbiota and Bacterial Translocation in the Pathogenesis of Liver Fibrosis.}, journal = {International journal of molecular sciences}, volume = {24}, number = {22}, pages = {}, pmid = {38003692}, issn = {1422-0067}, mesh = {Animals ; Humans ; *Gastrointestinal Microbiome ; Bacterial Translocation ; Liver Cirrhosis/pathology ; Liver/pathology ; *Liver Diseases/pathology ; Dysbiosis/microbiology ; }, abstract = {Cirrhosis is the end result of liver fibrosis in chronic liver diseases. Studying the mechanisms of its development and developing measures to slow down and regress it based on this knowledge seem to be important tasks for medicine. Currently, disorders of the gut-liver axis have great importance in the pathogenesis of cirrhosis. However, gut dysbiosis, which manifests as increased proportions in the gut microbiota of Bacilli and Proteobacteria that are capable of bacterial translocation and a decreased proportion of Clostridia that strengthen the intestinal barrier, occurs even at the pre-cirrhotic stage of chronic liver disease. This leads to the development of bacterial translocation, a process by which those microbes enter the blood of the portal vein and then the liver tissue, where they activate Kupffer cells through Toll-like receptor 4. In response, the Kupffer cells produce profibrogenic cytokines, which activate hepatic stellate cells, stimulating their transformation into myofibroblasts that produce collagen and other elements of the extracellular matrix. Blocking bacterial translocation with antibiotics, probiotics, synbiotics, and other methods could slow down the progression of liver fibrosis. This was shown in a number of animal models but requires further verification in long-term randomized controlled trials with humans.}, }
@article {pmid38003359, year = {2023}, author = {Siebieszuk, A and Sejbuk, M and Witkowska, AM}, title = {Studying the Human Microbiota: Advances in Understanding the Fundamentals, Origin, and Evolution of Biological Timekeeping.}, journal = {International journal of molecular sciences}, volume = {24}, number = {22}, pages = {}, pmid = {38003359}, issn = {1422-0067}, mesh = {Humans ; Oxidation-Reduction ; Circadian Rhythm/physiology ; *Circadian Clocks/genetics ; Protein Processing, Post-Translational ; *Microbiota ; }, abstract = {The recently observed circadian oscillations of the intestinal microbiota underscore the profound nature of the human-microbiome relationship and its importance for health. Together with the discovery of circadian clocks in non-photosynthetic gut bacteria and circadian rhythms in anucleated cells, these findings have indicated the possibility that virtually all microorganisms may possess functional biological clocks. However, they have also raised many essential questions concerning the fundamentals of biological timekeeping, its evolution, and its origin. This narrative review provides a comprehensive overview of the recent literature in molecular chronobiology, aiming to bring together the latest evidence on the structure and mechanisms driving microbial biological clocks while pointing to potential applications of this knowledge in medicine. Moreover, it discusses the latest hypotheses regarding the evolution of timing mechanisms and describes the functions of peroxiredoxins in cells and their contribution to the cellular clockwork. The diversity of biological clocks among various human-associated microorganisms and the role of transcriptional and post-translational timekeeping mechanisms are also addressed. Finally, recent evidence on metabolic oscillators and host-microbiome communication is presented.}, }
@article {pmid38002043, year = {2023}, author = {Rinaldi, F and Trink, A and Mondadori, G and Giuliani, G and Pinto, D}, title = {The Menopausal Transition: Is the Hair Follicle "Going through Menopause"?.}, journal = {Biomedicines}, volume = {11}, number = {11}, pages = {}, pmid = {38002043}, issn = {2227-9059}, abstract = {This article explores the link between menopause and changes in the hair follicle (HF) lifecycle, focusing on hormonal and metabolic dynamics. During menopause, hormonal fluctuations and aging can impact the HF, leading to phenomena such as thinning, loss of volume, and changes in hair texture. These changes are primarily attributed to a decrease in estrogen levels. However, not all women experience significant hair changes during menopause, and the extent of transformations can vary considerably from person to person, influenced by genetic factors, stress, diet, and other elements. Furthermore, menopause mirrors the aging process, affecting metabolism and blood flow to the HFs, influencing the availability of vital nutrients. The article also discusses the key role of energy metabolism in the HF lifecycle and the effect of hormones, particularly estrogens, on metabolic efficiency. The concept of a possible "menopause" clinically independent of menopause is introduced, related to changes in HF metabolism, emphasizing the importance of individual factors such as estrogen receptor responses, genetics, and last but not least, the microbiota in determining these dynamics.}, }
@article {pmid37998819, year = {2023}, author = {DuPont, HL and Salge, MMH}, title = {The Importance of a Healthy Microbiome in Pregnancy and Infancy and Microbiota Treatment to Reverse Dysbiosis for Improved Health.}, journal = {Antibiotics (Basel, Switzerland)}, volume = {12}, number = {11}, pages = {}, pmid = {37998819}, issn = {2079-6382}, abstract = {BACKGROUND: The microbiome of newborn infants during the first 1000 days, influenced early on by their mothers' microbiome health, mode of delivery and breast feeding, orchestrates the education and programming of the infant's immune system and determines in large part the general health of the infant for years.<br><br>METHODS: PubMed was reviewed for maternal infant microbiome health and microbiota therapy in this setting with prebiotics, probiotics, vaginal seeding and fecal microbiota transplantation (FMT).<br><br>RESULTS: A healthy nonobese mother, vaginal delivery and strict breast feeding contribute to microbiome health in a newborn and young infant. With reduced microbiome diversity (dysbiosis) during pregnancy, cesarean delivery, prematurity, and formula feeding contribute to dysbiosis in the newborn. Microbiota therapy is an important approach to repair dysbiosis in pregnant women and their infants. Currently available probiotics can have favorable metabolic effects on mothers and infants, but these effects are variable. In research settings, reversal of infant dysbiosis can be achieved via vaginal seeding or FMT. Next generation probiotics in development should replace current probiotics and FMT.<br><br>CONCLUSIONS: The most critical phase of human microbiome development is in the first 2-3 years of life. Preventing and treating dysbiosis during pregnancy and early life can have a profound effect on an infant's later health.}, }
@article {pmid37998794, year = {2023}, author = {Akomoneh, EA and Gestels, Z and Abdellati, S and Vereecken, K and Bartholomeeusen, K and Van den Bossche, D and Kenyon, C and Manoharan-Basil, SS}, title = {Genome Mining Uncovers NRPS and PKS Clusters in Rothia dentocariosa with Inhibitory Activity against Neisseria Species.}, journal = {Antibiotics (Basel, Switzerland)}, volume = {12}, number = {11}, pages = {}, pmid = {37998794}, issn = {2079-6382}, support = {2021//SOFI 2021 grant/ ; }, abstract = {The growing global threat of antimicrobial resistance is reaching a crisis point as common bacterial infections, including those caused by pathogenic Neisseria species, are becoming increasingly untreatable. This is compelling the scientific community to search for new antimicrobial agents, taking advantage of computational mining and using whole genome sequences to discover natural products from the human microbiome with antibiotic effects. In this study, we investigated the crude extract from a Rothia dentocariosa strain with demonstrated antimicrobial activity against pathogenic Neisseria spp. by spot-on-lawn assay. The genomic DNA of the R. dentocariosa strain was sequenced, and bioinformatic evaluation was performed using antiSMASH and PRISM to search for biosynthetic gene clusters (BGCs). The crude extract with potential antimicrobial activity was run on Tricine-SDS-PAGE, and the putative peptides were characterised using liquid chromatography-tandem mass spectrometry (LC-MS). The crude extract inhibited the growth of the pathogenic Neisseria spp. Six BGCs were identified corresponding to non-ribosomal peptide synthases (NRPSs), polyketide synthases (PKSs), and ribosomally synthesised and post-translationally modified peptides. Three peptides were also identified corresponding to Actinorhodin polyketide putative beta-ketoacyl synthase 1. These findings serve as a useful reference to facilitate the research and development of NRPS and PKS as antimicrobial products against multidrug-resistant N. gonorrhoeae.}, }
@article {pmid37997816, year = {2024}, author = {Kumavath, R and Pavithran, H and Paul, S and Anju, VT and Busi, S and Dyavaiah, M}, title = {Effects of gut microbiome and obesity on the development, progression and prevention of cancer (Review).}, journal = {International journal of oncology}, volume = {64}, number = {1}, pages = {}, doi = {10.3892/ijo.2023.5592}, pmid = {37997816}, issn = {1791-2423}, mesh = {Humans ; *Gastrointestinal Microbiome ; Dysbiosis ; Obesity/complications ; Carcinogenesis ; *Colorectal Neoplasms/metabolism ; *Liver Neoplasms ; }, abstract = {Cancer is one of the leading causes of death worldwide and it is estimated that the mortality rate of cancer will increase in the coming years. The etiology of the development and progression of cancer is multifactorial. Insights have been gained on the association between the human microbiome and tumor cell malignancy. A number of commensal microbe species are present in the human gut. They serve pivotal roles in maintaining several health and disease conditions, such as inflammatory bowel disease, irritable bowel syndrome, obesity and diabetes. Known major factors involved in cancer development include age, hormone levels, alcohol consumption, diet, being overweight, obesity, and infections, regardless of the type of cancer. Therefore, the present review aims to discuss the relationship between the gut microbiome and obesity‑associated malignancies, including colorectal, gastric and liver cancer. Obesity has been reported to contribute to the development of numerous types of cancer primarily caused by high fatty food intake. In addition, obesity‑associated microbiome alterations can lead to cancer and its progression. Dysbiosis of the gut microbiota can alter the metabolite profile, whilst increasing the levels of toxins, such as Bacteroides fragilis toxin and colibactin and cytolethal distending toxin, which are responsible for oncogenesis. The present review provides insights into the impact of gut microbiome dysbiosis on the progression of different types of cancers associated with obesity. It also discusses possible strategies for preserving a healthy gut microbiome. Different pre‑clinical and clinical models are available for studying cancer development downstream of gut microbiome dysbiosis. Furthermore, the role of metabolites or drugs employed in colorectal, gastric and liver cancer therapy would be discussed.}, }
@article {pmid37997472, year = {2023}, author = {Akbari, E and Milani, A and Seyedinkhorasani, M and Bolhassani, A}, title = {HPV co-infections with other pathogens in cancer development: A comprehensive review.}, journal = {Journal of medical virology}, volume = {95}, number = {11}, pages = {e29236}, doi = {10.1002/jmv.29236}, pmid = {37997472}, issn = {1096-9071}, mesh = {Female ; Humans ; *Papillomavirus Infections/complications ; *Coinfection ; *Epstein-Barr Virus Infections ; Herpesvirus 4, Human ; *Neoplasms/complications ; Papillomaviridae ; }, abstract = {High-risk human papillomaviruses (HR-HPVs) cause various malignancies in the anogenital and oropharyngeal regions. About 70% of cervical and oropharyngeal cancers are caused by HPV types 16 and 18. Notably, some viruses including herpes simplex virus, Epstein-Barr virus, and human immunodeficiency virus along with various bacteria often interact with HPV, potentially impacting its replication, persistence, and cancer progression. Thus, HPV infection can be significantly influenced by co-infecting agents that influence infection dynamics and disease progression. Bacterial co-infections (e.g., Chlamydia trachomatis) along with bacterial vaginosis-related species also interact with HPV in genital tract leading to viral persistence and disease outcomes. Co-infections involving HPV and diverse infectious agents have significant implications for disease transmission and clinical progression. This review explores multiple facets of HPV infection encompassing the co-infection dynamics with other pathogens, interaction with the human microbiome, and its role in disease development.}, }
@article {pmid37995844, year = {2023}, author = {Bonnici, V and Mengoni, C and Mangoni, M and Franco, G and Giugno, R}, title = {PanDelos-frags: A methodology for discovering pangenomic content of incomplete microbial assemblies.}, journal = {Journal of biomedical informatics}, volume = {148}, number = {}, pages = {104552}, doi = {10.1016/j.jbi.2023.104552}, pmid = {37995844}, issn = {1532-0480}, mesh = {Humans ; Ecosystem ; Genome ; *Genomics/methods ; Metagenomics/methods ; Software ; *Microbiota/genetics ; }, abstract = {Pangenomics was originally defined as the problem of comparing the composition of genes into gene families within a set of bacterial isolates belonging to the same species. The problem requires the calculation of sequence homology among such genes. When combined with metagenomics, namely for human microbiome composition analysis, gene-oriented pangenome detection becomes a promising method to decipher ecosystem functions and population-level evolution. Established computational tools are able to investigate the genetic content of isolates for which a complete genomic sequence is available. However, there is a plethora of incomplete genomes that are available on public resources, which only a few tools may analyze. Incomplete means that the process for reconstructing their genomic sequence is not complete, and only fragments of their sequence are currently available. However, the information contained in these fragments may play an essential role in the analyses. Here, we present PanDelos-frags, a computational tool which exploits and extends previous results in analyzing complete genomes. It provides a new methodology for inferring missing genetic information and thus for managing incomplete genomes. PanDelos-frags outperforms state-of-the-art approaches in reconstructing gene families in synthetic benchmarks and in a real use case of metagenomics. PanDelos-frags is publicly available at https://github.com/InfOmics/PanDelos-frags.}, }
@article {pmid37994755, year = {2023}, author = {Donato, K and Donato, K and Bonetti, G and Cristoni, S and Connelly, ST and Bertelli, M}, title = {Exploring the Impact of Tobacco Usage on Microbiome Dysbiosis and Associated Health Risks: A Comprehensive Review of Recent Advancements and Future Directions.}, journal = {La Clinica terapeutica}, volume = {174}, number = {Suppl 2(6)}, pages = {119-125}, doi = {10.7417/CT.2023.2478}, pmid = {37994755}, issn = {1972-6007}, mesh = {Humans ; Dysbiosis/microbiology ; *Microbiota ; *Colitis, Ulcerative ; *Crohn Disease ; }, abstract = {All over the world, tobacco usage is quickly expanding. Though it presents a major health risk and is anticipated to have long-lasting impacts on the public and economic health of the country, its consumers are increasing with every passing day. Tobacco is being used in a variety of ways, with cigarettes being the most popular. Smoking affects the healthy oral, intestinal, and pulmonary microbiomes, often altering the dynamic equilibrium of the diverse bacteria that make up the human microbiome, or "dysbiosis". Smoking-induced dysbiosis can lead to developing conditions like asthma, chronic obstructive pul-monary disease, Crohn's disease, ulcerative colitis, and periodontitis. The purpose of the following article is to provide a better and more comprehensive overview of the key areas that the tobacco industry needs to investigate, such as microbiome manipulation, to provide a complete picture of recent advancements in tobacco research while also keeping public safety in mind, and the various diseases linked to tobacco use.}, }
@article {pmid37994699, year = {2024}, author = {Hirsch, P and Tagirdzhanov, A and Kushnareva, A and Olkhovskii, I and Graf, S and Schmartz, GP and Hegemann, JD and Bozhüyük, KAJ and Müller, R and Keller, A and Gurevich, A}, title = {ABC-HuMi: the Atlas of Biosynthetic Gene Clusters in the Human Microbiome.}, journal = {Nucleic acids research}, volume = {52}, number = {D1}, pages = {D579-D585}, pmid = {37994699}, issn = {1362-4962}, support = {//Saarland University/ ; 466168626//DFG/ ; }, mesh = {Humans ; *Biosynthetic Pathways/genetics ; Computational Biology/instrumentation ; *Databases, Genetic ; Internet ; *Microbiota/genetics ; *Multigene Family/genetics ; Metagenome/genetics ; }, abstract = {The human microbiome has emerged as a rich source of diverse and bioactive natural products, harboring immense potential for therapeutic applications. To facilitate systematic exploration and analysis of its biosynthetic landscape, we present ABC-HuMi: the Atlas of Biosynthetic Gene Clusters (BGCs) in the Human Microbiome. ABC-HuMi integrates data from major human microbiome sequence databases and provides an expansive repository of BGCs compared to the limited coverage offered by existing resources. Employing state-of-the-art BGC prediction and analysis tools, our database ensures accurate annotation and enhanced prediction capabilities. ABC-HuMi empowers researchers with advanced browsing, filtering, and search functionality, enabling efficient exploration of the resource. At present, ABC-HuMi boasts a catalog of 19 218 representative BGCs derived from the human gut, oral, skin, respiratory and urogenital systems. By capturing the intricate biosynthetic potential across diverse human body sites, our database fosters profound insights into the molecular repertoire encoded within the human microbiome and offers a comprehensive resource for the discovery and characterization of novel bioactive compounds. The database is freely accessible at https://www.ccb.uni-saarland.de/abc_humi/.}, }
@article {pmid37986834, year = {2023}, author = {Wang, SH and Zheng, T and Fawzi, NL}, title = {Structure and position-specific interactions of prion-like domains in transcription factor Efg1 phase separation.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {37986834}, issn = {2692-8205}, support = {R01 GM147677/GM/NIGMS NIH HHS/United States ; }, abstract = {Candida albicans, a prominent member of the human microbiome, can make an opportunistic switch from commensal coexistence to pathogenicity accompanied by an epigenetic shift between the white and opaque cell states. This transcriptional switch is under precise regulation by a set of transcription factors (TFs), with Enhanced Filamentous Growth Protein 1 (Efg1) playing a central role. Previous research has emphasized the importance of Egf1's prion-like domain (PrLD) and the protein's ability to undergo phase separation for the white-to-opaque transition of C. albicans. However, the underlying molecular mechanisms of Efg1 phase separation have remained underexplored. In this study, we delved into the biophysical basis of Efg1 phase separation, revealing the significant contribution of both N-terminal (N) and C-terminal (C) PrLDs. Through NMR structural analysis, we found that Efg1 N-PrLD and C-PrLD are mostly disordered though have prominent partial α-helical secondary structures in both domains. NMR titration experiments suggest that the partially helical structures in N-PrLD act as hubs for self-interaction as well as Efg1 interaction with RNA. Using condensed-phase NMR spectroscopy, we uncovered diverse amino acid interactions underlying Efg1 phase separation. Particularly, we highlight the indispensable role of tyrosine residues within the transient α-helical structures of PrLDs particularly in the N-PrLD compared to the C-PrLD in stabilizing phase separation. Our study provides evidence that the transient α-helical structure is present in the phase separated state and highlights the particular importance of aromatic residues within these structures for phase separation. Together, these results enhance the understanding of C. albicans TF interactions that lead to virulence and provide a crucial foundation for potential antifungal therapies targeting the transcriptional switch.}, }
@article {pmid37978888, year = {2024}, author = {Cohen, DG and Wingert, RA}, title = {Forever young by Alpha(diversity)ville: restricting intestinal microbiome maturation stunts immune system development and increases susceptibility to infection.}, journal = {Tissue barriers}, volume = {12}, number = {3}, pages = {2281209}, pmid = {37978888}, issn = {2168-8370}, mesh = {Humans ; Disease Susceptibility ; *Gastrointestinal Microbiome/immunology/physiology ; Immune System/microbiology ; }, abstract = {The microbiome is a keystone of adult gastrointestinal (GI) tract health, where it facilitates digestion, wards off pathogen colonization, and exerts a powerful influence on the physiological health of organs ranging from the brain to the kidneys. From its establishment at birth and through the initial years of childhood, the human microbiome is particularly dynamic, shifting in its composition and alpha (species) diversity to an adult profile as dietary sustenance transitions from milk-based sources to others such as solid food. An innovative study has now demonstrated how microbiome maturation is requisite both for the progression of immune system development and for long-term gut barrier function. These insights have significant ramifications for designing pediatric approaches to cultivate immune cell ontogeny in the formative stages of human infancy.}, }
@article {pmid37978428, year = {2023}, author = {Garba, Z and Bonkoungou, IOJ and Millogo, NO and Natama, HM and Vokouma, PAP and Bonko, MDA and Karama, I and Tiendrebeogo, LAW and Haukka, K and Tinto, H and Sangaré, L and Barro, N}, title = {Wastewater from healthcare centers in Burkina Faso is a source of ESBL, AmpC-β-lactamase and carbapenemase-producing Escherichia coli and Klebsiella pneumoniae.}, journal = {BMC microbiology}, volume = {23}, number = {1}, pages = {351}, pmid = {37978428}, issn = {1471-2180}, mesh = {Humans ; Animals ; Escherichia coli ; Klebsiella pneumoniae ; Wastewater ; Burkina Faso ; Microbial Sensitivity Tests ; beta-Lactamases ; Bacterial Proteins ; Anti-Bacterial Agents/pharmacology ; *Escherichia coli Infections/microbiology ; Bacteria ; *Carbapenem-Resistant Enterobacteriaceae ; }, abstract = {BACKGROUND: Extended-spectrum β-lactamase (ESBL), plasmid-mediated AmpC-β-lactamase and carbapenemase-producing Escherichia coli and Klebsiella pneumoniae have spread into the environment worldwide posing a potential public health threat. However, the prevalence data for low- and middle-income countries are still scarce. The aim of this study was to evaluate the presence of ESBL, AmpC-β-lactamase and carbapenemase-producing and multidrug-resistant E. coli and K. pneumoniae in wastewaters from healthcare centers in Burkina Faso.<br><br>RESULTS: Eighty-four (84) wastewater samples were collected from five healthcare centers and plated on selective ESBL ChromAgar. E. coli and Klebsiella pneumoniae isolates were identified using API20E. ESBL-producing bacteria were detected in 97.6% of the samples and their average concentration per hospital ranged from 1.10&#x2009;&#xd7;&#x2009;10[5] to 5.23&#x2009;&#xd7;&#x2009;10[6]&#xa0;CFU/mL. Out of 170 putative ESBL-producing isolates (64% of them were E. coli) and 51 putative AmpC-&#x3b2;-lactamase-producing isolates, 95% and 45% were confirmed, respectively. Carbapenemase production was detected in 10 isolates, of which 6 were NDM producers, 3 were OXA-48 producers and 1 was NDM and OXA-48 producer. All isolates were multidrug resistant and, moreover, all of them were resistant to all tested &#x3b2;-lactams. Resistance to ESBL inhibitors was also common, up to 66% in E. coli and 62% in K. pneumoniae. Amikacin, fosfomycin and nitrofurantoin were the antibiotics to which the least resistance was detected.<br><br>CONCLUSIONS: This study showed that wastewater from healthcare centers constitutes a reservoir of multidrug-resistant bacteria in Burkina Faso, including carbapenemase producers. Untreated healthcare wastewater entering the environment exposes people and animals to infections caused by these multi-resistant bacteria, which are difficult to treat, especially in the resource-poor settings.}, }
@article {pmid37975292, year = {2024}, author = {Chmiel, JA and Stuivenberg, GA and Wong, JFW and Nott, L and Burton, JP and Razvi, H and Bjazevic, J}, title = {Predictive Modeling of Urinary Stone Composition Using Machine Learning and Clinical Data: Implications for Treatment Strategies and Pathophysiological Insights.}, journal = {Journal of endourology}, volume = {38}, number = {8}, pages = {778-787}, doi = {10.1089/end.2023.0446}, pmid = {37975292}, issn = {1557-900X}, mesh = {Humans ; *Machine Learning ; Male ; Female ; Middle Aged ; *Urinary Calculi/chemistry ; Calcium Oxalate ; Adult ; Calcium Phosphates ; Aged ; Uric Acid/urine ; Calcium/urine/blood ; Models, Biological ; }, abstract = {Purpose: Preventative strategies and surgical treatments for urolithiasis depend on stone composition. However, stone composition is often unknown until the stone is passed or surgically managed. Given that stone composition likely reflects the physiological parameters during its formation, we used clinical data from stone formers to predict stone composition. Materials and Methods: Data on stone composition, 24-hour urine, serum biochemistry, patient demographics, and medical history were prospectively collected from 777 kidney stone patients. Data were used to train gradient boosted machine and logistic regression models to distinguish calcium vs noncalcium, calcium oxalate monohydrate vs dihydrate, and calcium oxalate vs calcium phosphate vs uric acid stone types. Model performance was evaluated using the kappa score, and the influence of each predictor variable was assessed. Results: The calcium vs noncalcium model differentiated stone types with a kappa of 0.5231. The most influential predictors were 24-hour urine calcium, blood urate, and phosphate. The calcium oxalate monohydrate vs dihydrate model is the first of its kind and could discriminate stone types with a kappa of 0.2042. The key predictors were 24-hour urine urea, calcium, and oxalate. The multiclass model had a kappa of 0.3023 and the top predictors were age and 24-hour urine calcium and creatinine. Conclusions: Clinical data can be leveraged with machine learning algorithms to predict stone composition, which may help urologists determine stone type and guide their management plan before stone treatment. Investigating the most influential predictors of each classifier may improve the understanding of key clinical features of urolithiasis and shed light on pathophysiology.}, }
@article {pmid37973865, year = {2023}, author = {King, AM and Zhang, Z and Glassey, E and Siuti, P and Clardy, J and Voigt, CA}, title = {Systematic mining of the human microbiome identifies antimicrobial peptides with diverse activity spectra.}, journal = {Nature microbiology}, volume = {8}, number = {12}, pages = {2420-2434}, pmid = {37973865}, issn = {2058-5276}, support = {HR0011-15-C-0084//United States Department of Defense | Defense Advanced Research Projects Agency (DARPA)/ ; }, mesh = {Humans ; Antimicrobial Peptides ; *Methicillin-Resistant Staphylococcus aureus ; Escherichia coli ; Peptides/genetics/pharmacology/chemistry ; Bacteria/genetics ; *Microbiota/genetics ; Anti-Bacterial Agents/pharmacology ; }, abstract = {Human-associated bacteria secrete modified peptides to control host physiology and remodel the microbiota species composition. Here we scanned 2,229 Human Microbiome Project genomes of species colonizing skin, gastrointestinal tract, urogenital tract, mouth and trachea for gene clusters encoding RiPPs (ribosomally synthesized and post-translationally modified peptides). We found 218 lanthipeptides and 25 lasso peptides, 70 of which were synthesized and expressed in E. coli and 23 could be purified and functionally characterized. They were tested for activity against bacteria associated with healthy human flora and pathogens. New antibiotics were identified against strains implicated in skin, nasal and vaginal dysbiosis as well as from oral strains selectively targeting those in the gut. Extended- and narrow-spectrum antibiotics were found against methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococci. Mining natural products produced by human-associated microbes will enable the elucidation of ecological relationships and may be a rich resource for antimicrobial discovery.}, }
@article {pmid37969883, year = {2023}, author = {Azamfirei, L}, title = {The Human Microbiome in Intensive Care - A Journey Forward?.}, journal = {Journal of critical care medicine (Universitatea de Medicina si Farmacie din Targu-Mures)}, volume = {9}, number = {4}, pages = {205-207}, pmid = {37969883}, issn = {2393-1809}, }
@article {pmid37968359, year = {2024}, author = {Asnicar, F and Thomas, AM and Passerini, A and Waldron, L and Segata, N}, title = {Machine learning for microbiologists.}, journal = {Nature reviews. Microbiology}, volume = {22}, number = {4}, pages = {191-205}, pmid = {37968359}, issn = {1740-1534}, support = {R01 CA230551/CA/NCI NIH HHS/United States ; }, mesh = {Humans ; *Machine Learning ; *Microbiota ; }, abstract = {Machine learning is increasingly important in microbiology where it is used for tasks such as predicting antibiotic resistance and associating human microbiome features with complex host diseases. The applications in microbiology are quickly expanding and the machine learning tools frequently used in basic and clinical research range from classification and regression to clustering and dimensionality reduction. In this Review, we examine the main machine learning concepts, tasks and applications that are relevant for experimental and clinical microbiologists. We provide the minimal toolbox for a microbiologist to be able to understand, interpret and use machine learning in their experimental and translational activities.}, }
@article {pmid37965266, year = {2023}, author = {Piazzesi, A and Pane, S and Russo, A and Del Chierico, F and Francalanci, P and Cotugno, N and Rossi, P and Locatelli, F and Palma, P and Putignani, L}, title = {Case Report: The impact of severe cryptosporidiosis on the gut microbiota of a pediatric patient with CD40L immunodeficiency.}, journal = {Frontiers in cellular and infection microbiology}, volume = {13}, number = {}, pages = {1281440}, pmid = {37965266}, issn = {2235-2988}, mesh = {Animals ; Humans ; Child ; Child, Preschool ; *Cryptosporidiosis/complications/parasitology ; CD40 Ligand ; *Gastrointestinal Microbiome ; *Cryptosporidium/genetics ; Intestines/microbiology ; *Immunologic Deficiency Syndromes/complications ; *Parasites ; *Cryptosporidium parvum ; Bacteria/genetics ; Propionibacterium acnes ; }, abstract = {Cryptosporidium parvum is a protozoan parasite and one of the leading causes of gastroenteritis in the world, primarily affecting very young children and immunocompromised patients. While infection is usually self-limiting, it can become chronic and even lethal in these vulnerable populations, in whom Cryptosporidium treatments are generally ineffective, due to their acting in concert with a functioning immune system. Here, we describe a case of chronic cryptosporidiosis in a European child with severe CD40L immunodeficiency infected with Cryptosporidium parvum of the IIa20G1 subgenotype, a lineage which has thus far only ever been described in the Middle East. After years of on-off treatment with conventional and non-conventional anti-parasitic drugs failed to clear parasitosis, we performed targeted metagenomics to observe the bacterial composition of the patient's gut microbiota (GM), and to evaluate fecal microbiota transplantation (FMT) as a potential treatment option. We found that C. parvum infection led to significant shifts in GM bacterial composition in our patient, with consequent shifts in predicted intestinal functional signatures consistent with a state of persistent inflammation. This, combined with the patient's poor prognosis and increasing parasitic burden despite many rounds of anti-parasitic drug treatments, made the patient a potential candidate for an experimental FMT procedure. Unfortunately, given the many comorbidities that were precipitated by the patient's immunodeficiency and chronic C. parvum infection, FMT was postponed in favor of more urgently necessary liver and bone marrow transplants. Tragically, after the first liver transplant failed, the patient lost his life before undergoing FMT and a second liver transplant. With this case report, we present the first description of how cryptosporidiosis can shape the gut microbiota of a pediatric patient with severe immunodeficiency. Finally, we discuss how both our results and the current scientific literature suggest that GM modulations, either by probiotics or FMT, can become novel treatment options for chronic Cryptosporidium infection and its consequent complications, especially in those patients who do not respond to the currently available anti-parasitic therapies.}, }
@article {pmid37963399, year = {2024}, author = {Jennings, SAV and Clavel, T}, title = {Synthetic Communities of Gut Microbes for Basic Research and Translational Approaches in Animal Health and Nutrition.}, journal = {Annual review of animal biosciences}, volume = {12}, number = {}, pages = {283-300}, doi = {10.1146/annurev-animal-021022-025552}, pmid = {37963399}, issn = {2165-8110}, mesh = {Humans ; Animals ; Mice ; *Gastrointestinal Microbiome ; Reproducibility of Results ; Nutritional Status ; }, abstract = {Microbes and animals have a symbiotic relationship that greatly influences nutrient uptake and animal health. This relationship can be studied using selections of microbes termed synthetic communities, or SynComs. SynComs are used in many different animal hosts, including agricultural animals, to investigate microbial interactions with nutrients and how these affect animal health. The most common host focuses for SynComs are currently mouse and human, from basic mechanistic research through to translational disease models and live biotherapeutic products (LBPs) as treatments. We discuss SynComs used in basic research models and findings that relate to human and animal health and nutrition. Translational use cases of SynComs are discussed, followed by LBPs, especially within the context of agriculture. SynComs still face challenges, such as standardization for reproducibility and contamination risks. However, the future of SynComs is hopeful, especially in the areas of genome-guided SynCom design and custom SynCom-based treatments.}, }
@article {pmid37961318, year = {2023}, author = {Walker, AC and Bhargava, R and Bucher, M and Brust, AS and Czy, DM}, title = {Identification of proteotoxic and proteoprotective bacteria that non-specifically affect proteins associated with neurodegenerative diseases.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {37961318}, issn = {2692-8205}, support = {P40 OD010440/OD/NIH HHS/United States ; R03 AG070580/AG/NIA NIH HHS/United States ; }, abstract = {Neurodegenerative protein conformational diseases (PCDs), such as Alzheimer's, Parkinson's, and Huntington's, are a leading cause of death and disability worldwide and have no known cures or effective treatments. Emerging evidence suggests a role for the gut microbiota in the pathogenesis of neurodegenerative PCDs; however, the influence of specific bacteria on the culprit proteins associated with each of these diseases remains elusive, primarily due to the complexity of the microbiota. In the present study, we employed a single-strain screening approach to identify human bacterial isolates that enhance or suppress the aggregation of culprit proteins and the associated toxicity in Caenorhabditis elegans expressing Aβ1-42, α-synuclein, and polyglutamine tracts. Here, we reveal the first comprehensive analysis of the human microbiome for its effect on proteins associated with neurodegenerative diseases. Our results suggest that bacteria affect the aggregation of metastable proteins by modulating host proteostasis rather than selectively targeting specific disease-associated proteins. These results reveal bacteria that potentially influence the pathogenesis of PCDs and open new promising prevention and treatment opportunities by altering the abundance of beneficial and detrimental microbes.}, }
@article {pmid37958613, year = {2023}, author = {Mäenpää, K and Ilves, M and Zhao, L and Alenius, H and Sinkko, H and Karisola, P}, title = {Effects of Superficial Scratching and Engineered Nanomaterials on Skin Gene Profiles and Microbiota in SKH-1 Mice.}, journal = {International journal of molecular sciences}, volume = {24}, number = {21}, pages = {}, pmid = {37958613}, issn = {1422-0067}, support = {307768//Academy of Finland/ ; 1333178//Academy of Finland/ ; Personal funding//Finnish Cultural Foundation/ ; }, mesh = {Mice ; Animals ; *Skin/metabolism ; Wound Healing ; Administration, Cutaneous ; *Microbiota ; Neutrophils ; }, abstract = {Scratching damages upper layers of the skin, breaks this first line of immune defence, and leads to inflammation response, which often also modifies the microbiota of the skin. Although the healing of incision wounds is well-described, there are fewer studies on superficial wounds. We used a simulated model of skin scratching to study changes in the host transcriptome, skin microbiota, and their relationship. Additionally, we examined the effect of nanosized ZnO, TiO2, and Ag on both intact and damaged skin. At 24 h after exposure, the number of neutrophils was increased, 396 genes were differentially expressed, and microbiota compositions changed between scratched and intact control skin. At 7 d, the skin was still colonised by gut-associated microbes, including Lachnospiraceae, present in the cage environment, while the transcriptomic responses decreased. To sum up, the nanomaterial exposures reduced the relative abundance of cutaneous microbes on healthy skin, but the effect of scratching was more significant for the transcriptome than the nanomaterial exposure both at 24 h and 7 d. We conclude that superficial skin scratching induces inflammatory cell accumulation and changes in gene expression especially at 24 h, while the changes in the microbiota last at least 7 days.}, }
@article {pmid37950262, year = {2023}, author = {Smajdor, J and Jedlińska, K and Porada, R and Górska-Ratusznik, A and Policht, A and Śróttek, M and Więcek, G and Baś, B and Strus, M}, title = {The impact of gut bacteria producing long chain homologs of vitamin K2 on colorectal carcinogenesis.}, journal = {Cancer cell international}, volume = {23}, number = {1}, pages = {268}, pmid = {37950262}, issn = {1475-2867}, support = {2018/31/B/NZ6/02472//Narodowym Centrum Nauki/ ; 2018/31/B/NZ6/02472//Narodowym Centrum Nauki/ ; 2018/31/B/NZ6/02472//Narodowym Centrum Nauki/ ; 2018/31/B/NZ6/02472//Narodowym Centrum Nauki/ ; 2018/31/B/NZ6/02472//Narodowym Centrum Nauki/ ; 2018/31/B/NZ6/02472//Narodowym Centrum Nauki/ ; 2018/31/B/NZ6/02472//Narodowym Centrum Nauki/ ; }, abstract = {Colorectal cancer (CRC) is one of the foremost causes of cancer-related deaths. Lately, a close connection between the course of CRC and the intestinal microbiota has been revealed. Vitamin K2 (VK2) is a bacterially derived compound that plays a crucial role in the human body. Its significant anti-cancer properties may result, inter alia, from a quinone ring possessing a specific chemical structure found in many chemotherapeutics. VK2 can be supplied to our body exogenously, i.e., through dietary supplements or fermented food (e.g., yellow cheese, fermented soybeans -Natto), and endogenously, i.e., through the production of bacteria that constantly colonize the human microbiome of the large intestine.This paper focuses on endogenous K2 synthesized by the most active members of the human gut microbiome. This analysis tested 86 intestinally derived bacterial strains, among which the largest VK2 producers (Lactobacillus, Bifidobacterium, Bacillus) were selected. Moreover, based on the chosen VK2-MK4 homolog, the potential of VK2 penetration into Caco-2 cells in an aqueous environment without the coexistence of fats, pancreatic enzymes, or bile salts has been displayed. The influence of three VK2 homologs: VK2-MK4, VK2-MK7 and VK2-MK9 on apoptosis and necrosis of Caco-2 cells was tested proving the lack of their harmful effects on the tested cells. Moreover, the unique role of long-chain homologs (VK2-MK9 and VK2-MK7) in inhibiting the secretion of pro-inflammatory cytokines such as IL-8 (for Caco-2 tissue) and IL-6 and TNFα (for RAW 264.7) has been documented.}, }
@article {pmid37950236, year = {2023}, author = {Zhou, X and You, L and Xin, Z and Su, H and Zhou, J and Ma, Y}, title = {Leveraging circulating microbiome signatures to predict tumor immune microenvironment and prognosis of patients with non-small cell lung cancer.}, journal = {Journal of translational medicine}, volume = {21}, number = {1}, pages = {800}, pmid = {37950236}, issn = {1479-5876}, mesh = {Humans ; *Carcinoma, Non-Small-Cell Lung ; Tumor Microenvironment ; *Lung Neoplasms ; Prognosis ; *Microbiota ; }, abstract = {BACKGROUND: Accumulating evidence supports the significant role of human microbiome in development and therapeutic response of tumors. Circulating microbial DNA is non-invasive and could show a general view of the microbiome of host, making it a promising biomarker for cancers. However, whether circulating microbiome is associated with prognosis of non-small cell lung cancer (NSCLC) and its potential mechanisms on tumor immune microenvironment still remains unknown.<br><br>METHODS: The blood microbiome data and matching tumor RNA-seq data of TCGA NSCLC patients were obtained from Poore's study and UCSC Xena. Univariate and multivariate Cox regression analysis were used to identify circulating microbiome signatures associated with overall survival (OS) and construct the circulating microbial abundance prognostic scoring (MAPS) model. Nomograms integrating clinical characteristics and circulating MAPS scores were established to predict OS rate of NSCLC patients. Joint analysis of blood microbiome data and matching tumor RNA-seq data was used to deciphered the tumor microenvironment landscape of patients in circulating MAPS-high and MAPS-low groups. Finally, the predictive value of circulating MAPS on the efficacy of immunotherapy and chemotherapy were assessed.<br><br>RESULTS: A circulating MAPS prediction model consisting of 14 circulating microbes was constructed and had an independent prognostic value for NSCLC. The integration of circulating MAPS into nomograms may improve the prognosis predictive power. Joint analysis revealed potential interactions between prognostic circulating microbiome and tumor immune microenvironment. Especially, intratumor plasma cells and humoral immune response were enriched in circulating MAPS-low group, while intratumor CD4&#x2009;+&#x2009;Th2 cells and proliferative related pathways were enriched in MAPS-high group. Finally, drug sensitivity analysis indicated the potential of circulating MAPS as a predictor of chemotherapy efficacy.<br><br>CONCLUSION: A circulating MAPS prediction model was constructed successfully and showed great prognostic value for NSCLC. Our study provides new insights of interactions between microbes, tumors and immunity, and may further contribute to precision medicine for NSCLC.}, }
@article {pmid37941395, year = {2022}, author = {Blumberg, K and Miller, M and Ponsero, A and Hurwitz, B}, title = {Ontology-driven analysis of marine metagenomics: what more can we learn from our data?.}, journal = {GigaScience}, volume = {12}, number = {}, pages = {}, pmid = {37941395}, issn = {2047-217X}, mesh = {*Ecology ; *Microbiota/genetics ; Metagenome ; Metagenomics ; }, abstract = {BACKGROUND: The proliferation of metagenomic sequencing technologies has enabled novel insights into the functional genomic potentials and taxonomic structure of microbial communities. However, cyberinfrastructure efforts to manage and enable the reproducible analysis of sequence data have not kept pace. Thus, there is increasing recognition of the need to make metagenomic data discoverable within machine-searchable frameworks compliant with the FAIR (Findability, Accessibility, Interoperability, and Reusability) principles for data stewardship. Although a variety of metagenomic web services exist, none currently leverage the hierarchically structured terminology encoded within common life science ontologies to programmatically discover data.<br><br>RESULTS: Here, we integrate large-scale marine metagenomic datasets with community-driven life science ontologies into a novel FAIR web service. This approach enables the retrieval of data discovered by intersecting the knowledge represented within ontologies against the functional genomic potential and taxonomic structure computed from marine sequencing data. Our findings highlight various microbial functional and taxonomic patterns relevant to the ecology of prokaryotes in various aquatic environments.<br><br>CONCLUSIONS: In this work, we present and evaluate a novel Semantic Web architecture that can be used to ask novel biological questions of existing marine metagenomic datasets. Finally, the FAIR ontology searchable data products provided by our API can be leveraged by future research efforts.}, }
@article {pmid37929823, year = {2024}, author = {Yi, X and Lu, H and Liu, X and He, J and Li, B and Wang, Z and Zhao, Y and Zhang, X and Yu, X}, title = {Unravelling the enigma of the human microbiome: Evolution and selection of sequencing technologies.}, journal = {Microbial biotechnology}, volume = {17}, number = {1}, pages = {e14364}, pmid = {37929823}, issn = {1751-7915}, support = {82202569//National Natural Science Foundation of China/ ; 20210302124635//Shanxi Province Basic Research Program Project/ ; }, mesh = {Humans ; *Microbiota ; Metagenome ; High-Throughput Nucleotide Sequencing/methods ; Metagenomics ; Technology ; }, abstract = {The human microbiome plays a crucial role in maintaining health, with advances in high-throughput sequencing technology and reduced sequencing costs triggering a surge in microbiome research. Microbiome studies generally incorporate five key phases: design, sampling, sequencing, analysis, and reporting, with sequencing strategy being a crucial step offering numerous options. Present mainstream sequencing strategies include Amplicon sequencing, Metagenomic Next-Generation Sequencing (mNGS), and Targeted Next-Generation Sequencing (tNGS). Two innovative technologies recently emerged, namely MobiMicrobe high-throughput microbial single-cell genome sequencing technology and 2bRAD-M simplified metagenomic sequencing technology, compensate for the limitations of mainstream technologies, each boasting unique core strengths. This paper reviews the basic principles and processes of these three mainstream and two novel microbiological technologies, aiding readers in understanding the benefits and drawbacks of different technologies, thereby guiding the selection of the most suitable method for their research endeavours.}, }
@article {pmid37923896, year = {2023}, author = {Marzano, V and Levi Mortera, S and Vernocchi, P and Del Chierico, F and Marangelo, C and Guarrasi, V and Gardini, S and Dentici, ML and Capolino, R and Digilio, MC and Di Donato, M and Spasari, I and Abreu, MT and Dallapiccola, B and Putignani, L}, title = {Williams-Beuren syndrome shapes the gut microbiota metaproteome.}, journal = {Scientific reports}, volume = {13}, number = {1}, pages = {18963}, pmid = {37923896}, issn = {2045-2322}, mesh = {Humans ; *Williams Syndrome ; *Gastrointestinal Microbiome ; Bacteria/genetics ; Firmicutes ; Gastrointestinal Tract ; }, abstract = {Williams-Beuren syndrome (WBS) is a rare genetic neurodevelopmental disorder with multi-systemic manifestations. The evidence that most subjects with WBS face gastrointestinal (GI) comorbidities, have prompted us to carry out a metaproteomic investigation of their gut microbiota (GM) profile compared to age-matched healthy subjects (CTRLs). Metaproteomic analysis was carried out on fecal samples collected from 41 individuals with WBS, and compared with samples from 45 CTRLs. Stool were extracted for high yield in bacterial protein group (PG) content, trypsin-digested and analysed by nanoLiquid Chromatography-Mass Spectrometry. Label free quantification, taxonomic assignment by the lowest common ancestor (LCA) algorithm and functional annotations by COG and KEGG databases were performed. Data were statistically interpreted by multivariate and univariate analyses. A WBS GM functional dissimilarity respect to CTRLs, regardless age distribution, was reported. The alterations in function of WBSs GM was primarily based on bacterial pathways linked to carbohydrate transport and metabolism and energy production. Influence of diet, obesity, and GI symptoms was assessed, highlighting changes in GM biochemical patterns, according to WBS subsets' stratification. The LCA-derived ecology unveiled WBS-related functionally active bacterial signatures: Bacteroidetes related to over-expressed PGs, and Firmicutes, specifically the specie Faecalibacterium prausnitzii, linked to under-expressed PGs, suggesting a depletion of beneficial bacteria. These new evidences on WBS gut dysbiosis may offer novel targets for tailored interventions.}, }
@article {pmid37923839, year = {2024}, author = {Routy, B and Lenehan, JG and Miller, WH and Jamal, R and Messaoudene, M and Daisley, BA and Hes, C and Al, KF and Martinez-Gili, L and Punčochář, M and Ernst, S and Logan, D and Belanger, K and Esfahani, K and Richard, C and Ninkov, M and Piccinno, G and Armanini, F and Pinto, F and Krishnamoorthy, M and Figueredo, R and Thebault, P and Takis, P and Magrill, J and Ramsay, L and Derosa, L and Marchesi, JR and Parvathy, SN and Elkrief, A and Watson, IR and Lapointe, R and Segata, N and Haeryfar, SMM and Mullish, BH and Silverman, MS and Burton, JP and Maleki Vareki, S}, title = {Author Correction: Fecal microbiota transplantation plus anti-PD-1 immunotherapy in advanced melanoma: a phase I trial.}, journal = {Nature medicine}, volume = {30}, number = {2}, pages = {604}, doi = {10.1038/s41591-023-02650-8}, pmid = {37923839}, issn = {1546-170X}, }
@article {pmid37921025, year = {2024}, author = {Qiao, X and He, H and Sun, L and Bai, S and Ye, P}, title = {Testing latent classes in gut microbiome data using generalized Poisson regression models.}, journal = {Statistics in medicine}, volume = {43}, number = {1}, pages = {102-124}, doi = {10.1002/sim.9944}, pmid = {37921025}, issn = {1097-0258}, support = {P20GM109036/GF/NIH HHS/United States ; }, mesh = {Humans ; Models, Statistical ; *Gastrointestinal Microbiome ; Computer Simulation ; *Microbiota ; Longitudinal Studies ; Poisson Distribution ; }, abstract = {Human microbiome research has gained increasing importance due to its critical roles in comprehending human health and disease. Within the realm of microbiome research, the data generated often involves operational taxonomic unit counts, which can frequently present challenges such as over-dispersion and zero-inflation. To address dispersion-related concerns, the generalized Poisson model offers a flexible solution, effectively handling data characterized by over-dispersion, equi-dispersion, and under-dispersion. Furthermore, the realm of zero-inflated generalized Poisson models provides a strategic avenue to simultaneously tackle both over-dispersion and zero-inflation. The phenomenon of zero-inflation frequently stems from the heterogeneous nature of study populations. It emerges when specific microbial taxa fail to thrive in the microbial community of certain subjects, consequently resulting in a consistent count of zeros for these individuals. This subset of subjects represents a latent class, where their zeros originate from the genuine absence of the microbial taxa. In this paper, we introduce a novel testing methodology designed to uncover such latent classes within generalized Poisson regression models. We establish a closed-form test statistic and deduce its asymptotic distribution based on estimating equations. To assess its efficacy, we conduct an extensive array of simulation studies, and further apply the test to detect latent classes in human gut microbiome data from the Bogalusa Heart Study.}, }
@article {pmid37918889, year = {2023}, author = {Thomas, SC and Miller, G and Li, X and Saxena, D}, title = {Getting off tract: contributions of intraorgan microbiota to cancer in extraintestinal organs.}, journal = {Gut}, volume = {73}, number = {1}, pages = {175-185}, pmid = {37918889}, issn = {1468-3288}, support = {R01 CA206105/CA/NCI NIH HHS/United States ; R41 CA250892/CA/NCI NIH HHS/United States ; }, mesh = {Humans ; *Microbiota ; *Gastrointestinal Microbiome ; *Mycobiome ; Virome ; *Neoplasms/etiology ; }, abstract = {The gastrointestinal ecosystem has received the most attention when examining the contributions of the human microbiome to health and disease. This concentration of effort is logical due to the overwhelming abundance of microbes in the gut coupled with the relative ease of sampling compared with other organs. However, the intestines are intimately connected to multiple extraintestinal organs, providing an opportunity for homeostatic microbial colonisation and pathogenesis in organs traditionally thought to be sterile or only transiently harbouring microbiota. These habitats are challenging to sample, and their low microbial biomass among large amounts of host tissue can make study challenging. Nevertheless, recent findings have shown that many extraintestinal organs that are intimately linked to the gut harbour stable microbiomes, which are colonised from the gut in selective manners and have highlighted not just the influence of the bacteriome but that of the mycobiome and virome on oncogenesis and health.}, }
@article {pmid37908308, year = {2023}, author = {Celoria, V and Rosset, F and Pala, V and Dapavo, P and Ribero, S and Quaglino, P and Mastorino, L}, title = {The Skin Microbiome and Its Role in Psoriasis: A Review.}, journal = {Psoriasis (Auckland, N.Z.)}, volume = {13}, number = {}, pages = {71-78}, pmid = {37908308}, issn = {2230-326X}, abstract = {The skin microbiome is made of various microorganisms, most of which have the function of protecting individuals from harmful pathogens, and they are involved in innate and adaptive immune responses. The skin acts as a physical and immunological barrier against external stimuli, including pathogens and physical damage. Changes in the composition of the skin microbiome can trigger inflammatory processes leading to inflammatory skin diseases in susceptible individuals. Psoriasis (PsO) is a chronic inflammatory disease with a multifactorial etiology, where breakdown of immune tolerance to cutaneous microorganisms is implicated in its pathogenesis. Dysregulation of the microbiome due to genetic and environmental factors plays a significant role in the development of psoriatic disease. Dermatologic conditions such as atopic dermatitis, acne, psoriasis, and rosacea have been associated with intestinal dysbiosis. The skin microbiota composition is crucial for the development of appropriate immune responses, and alterations in the skin microbiome can contribute to changes in physiology and susceptibility to skin diseases or inflammatory conditions. Understanding the microbial settlement of the skin and the network of interactions that occur throughout life is essential for comprehending the pathogenesis of skin diseases and developing innovative treatments. With this article we tried to explore the relationship between the human microbiome and psoriatic disease, shedding light on the functions of the microbiome and the inflammatory disease processes to identify additional therapeutic targets. This review aims to highlight the relationship between skin and gut microbiome functions and inflammatory processes in skin psoriasis and psoriatic arthritis (PsA). The goal is to facilitate future studies on the skin microbiome to identify potential novel therapies for patients with psoriatic disease.}, }
@article {pmid37906201, year = {2024}, author = {Hussein, N and Rajasuriar, R and Khan, AM and Lim, YA and Gan, GG}, title = {The Role of the Gut Microbiome in Hematological Cancers.}, journal = {Molecular cancer research : MCR}, volume = {22}, number = {1}, pages = {7-20}, doi = {10.1158/1541-7786.MCR-23-0080}, pmid = {37906201}, issn = {1557-3125}, support = {FRGS/1/2019/SKK06/UM/01/2//Ministry of Higher Education, Malaysia (MOHE)/ ; }, mesh = {Humans ; *Gastrointestinal Microbiome ; Dysbiosis/microbiology/therapy ; *Microbiota ; Inflammation ; *Hematologic Neoplasms ; }, abstract = {Humans are in a complex symbiotic relationship with a wide range of microbial organisms, including bacteria, viruses, and fungi. The evolution and composition of the human microbiome can be an indicator of how it may affect human health and susceptibility to diseases. Microbiome alteration, termed as dysbiosis, has been linked to the pathogenesis and progression of hematological cancers. A variety of mechanisms, including epithelial barrier disruption, local chronic inflammation response trigger, antigen dis-sequestration, and molecular mimicry, have been proposed to be associated with gut microbiota. Dysbiosis may be induced or worsened by cancer therapies (such as chemotherapy and/or hematopoietic stem cell transplantation) or infection. The use of antibiotics during treatment may also promote dysbiosis, with possible long-term consequences. The aim of this review is to provide a succinct summary of the current knowledge describing the role of the microbiome in hematological cancers, as well as its influence on their therapies. Modulation of the gut microbiome, involving modifying the composition of the beneficial microorganisms in the management and treatment of hematological cancers is also discussed. Additionally discussed are the latest developments in modeling approaches and tools used for computational analyses, interpretation and better understanding of the gut microbiome data.}, }
@article {pmid37904958, year = {2023}, author = {Mishra, AK and Mahmud, I and Lorenzi, PL and Jenq, RR and Wargo, JA and Ajami, NJ and Peterson, CB}, title = {TARO: tree-aggregated factor regression for microbiome data integration.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2023.10.17.562792}, pmid = {37904958}, issn = {2692-8205}, support = {R01 CA244845/CA/NCI NIH HHS/United States ; }, abstract = {MOTIVATION: Although the human microbiome plays a key role in health and disease, the biological mechanisms underlying the interaction between the microbiome and its host are incompletely understood. Integration with other molecular profiling data offers an opportunity to characterize the role of the microbiome and elucidate therapeutic targets. However, this remains challenging to the high dimensionality, compositionality, and rare features found in microbiome profiling data. These challenges necessitate the use of methods that can achieve structured sparsity in learning cross-platform association patterns.<br><br>RESULTS: We propose Tree-Aggregated factor RegressiOn (TARO) for the integration of microbiome and metabolomic data. We leverage information on the phylogenetic tree structure to flexibly aggregate rare features. We demonstrate through simulation studies that TARO accurately recovers a low-rank coefficient matrix and identifies relevant features. We applied TARO to microbiome and metabolomic profiles gathered from subjects being screened for colorectal cancer to understand how gut microrganisms shape intestinal metabolite abundances.<br><br>The R package TARO implementing the proposed methods is available online at https://github.com/amishra-stats/taro-package .}, }
@article {pmid37895330, year = {2023}, author = {Vata, D and Tarcau, BM and Popescu, IA and Halip, IA and Patrascu, AI and Gheuca Solovastru, DF and Mocanu, M and Chiriac, PC and Gheuca Solovastru, L}, title = {Update on Obesity in Psoriasis Patients.}, journal = {Life (Basel, Switzerland)}, volume = {13}, number = {10}, pages = {}, pmid = {37895330}, issn = {2075-1729}, abstract = {Psoriasis is a chronic inflammatory skin condition, with genetic, epigenetic, environmental, and lifestyle factors contributing to its onset and recurrence. Severe psoriasis has a great impact on quality of life, which is similar to that of insulin-dependent diabetes, depression, and ischemic heart disease, but with a lower mortality. There is an overlap between the rising incidences of autoimmune diseases and obesity. In recent years, research has shown that there is an association between psoriasis and obesity. Psoriasis is linked to obesity in a two-way manner, as each can precipitate the development of the other. Several adipose tissue-secreted adipokines were shown to be elevated in obese psoriasis patients, exhibiting similar mechanisms of action to those underlying the pathogenesis of psoriasis. Excess body weight can influence not only the treatment response in psoriasis, but also the adverse events, leading to decreased patient compliance. Specific human microbiome patterns have been identified for obesity and psoriasis and could represent a future therapeutic target in selected individuals.}, }
@article {pmid37895286, year = {2023}, author = {Aboushaala, K and Wong, AYL and Barajas, JN and Lim, P and Al-Harthi, L and Chee, A and Forsyth, CB and Oh, CD and Toro, SJ and Williams, FMK and An, HS and Samartzis, D}, title = {The Human Microbiome and Its Role in Musculoskeletal Disorders.}, journal = {Genes}, volume = {14}, number = {10}, pages = {}, pmid = {37895286}, issn = {2073-4425}, support = {R21 AR079679/AR/NIAMS NIH HHS/United States ; }, mesh = {Humans ; *Microbiota ; *Gastrointestinal Microbiome ; Gastrointestinal Tract/microbiology ; Bacteria ; *Musculoskeletal Diseases ; Oxygen ; }, abstract = {Musculoskeletal diseases (MSDs) are characterized as injuries and illnesses that affect the musculoskeletal system. MSDs affect every population worldwide and are associated with substantial global burden. Variations in the makeup of the gut microbiota may be related to chronic MSDs. There is growing interest in exploring potential connections between chronic MSDs and variations in the composition of gut microbiota. The human microbiota is a complex community consisting of viruses, archaea, bacteria, and eukaryotes, both inside and outside of the human body. These microorganisms play crucial roles in influencing human physiology, impacting metabolic and immunological systems in health and disease. Different body areas host specific types of microorganisms, with facultative anaerobes dominating the gastrointestinal tract (able to thrive with or without oxygen), while strict aerobes prevail in the nasal cavity, respiratory tract, and skin surfaces (requiring oxygen for development). Together with the immune system, these bacteria have coevolved throughout time, forming complex biological relationships. Changes in the microbial ecology of the gut may have a big impact on health and can help illnesses develop. These changes are frequently impacted by lifestyle choices and underlying medical disorders. The potential for safety, expenses, and efficacy of microbiota-based medicines, even with occasional delivery, has attracted interest. They are, therefore, a desirable candidate for treating MSDs that are chronic and that may have variable progression patterns. As such, the following is a narrative review to address the role of the human microbiome as it relates to MSDs.}, }
@article {pmid37894256, year = {2023}, author = {Ye, C and Dong, C and Lin, Y and Shi, H and Zhou, W}, title = {Interplay between the Human Microbiome and Biliary Tract Cancer: Implications for Pathogenesis and Therapy.}, journal = {Microorganisms}, volume = {11}, number = {10}, pages = {}, pmid = {37894256}, issn = {2076-2607}, support = {82260555//the National Natural Science Foundation of China/ ; ldyyyn2021-78//the First Hospital of Lanzhou University Intra-Hospital Fund Youth Fund/ ; 2022B-027//the Education Department of Gansu Province: Innovation Fund Project/ ; }, abstract = {Biliary tract cancer, encompassing intrahepatic and extrahepatic cholangiocarcinoma as well as gallbladder carcinoma, stands as a prevalent malignancy characterized by escalating incidence rates and unfavorable prognoses. The onset of cholangiocarcinoma involves a multitude of risk factors and could potentially be influenced by microbial exposure. The human microbiome, encompassing the entirety of human microbial genetic information, assumes a pivotal role in regulating key aspects such as host digestion, absorption, immune responses, and metabolism. The widespread application of next-generation sequencing technology has notably propelled investigations into the intricate relationship between the microbiome and diseases. An accumulating body of evidence strongly suggests a profound interconnection between biliary tract cancer and the human microbiome. This article critically appraises the existing evidence pertaining to the microbiome milieu within patients afflicted by biliary tract cancer. Furthermore, it delves into potential mechanisms through which dysregulation of the human microbiome could contribute to the advancement of biliary tract cancer. Additionally, the article expounds on its role in the context of chemotherapy and immunotherapy for biliary tract cancer.}, }
@article {pmid37894194, year = {2023}, author = {Lopetuso, LR and Laterza, L and Petito, V and Pecere, S and Quaranta, G and Del Chierico, F and Puca, P and Schiavoni, E and Napolitano, D and Poscia, A and Ianiro, G and Pugliese, D and Putignani, L and Sanguinetti, M and Armuzzi, A and Masucci, L and Gasbarrini, A and Cammarota, G and Scaldaferri, F}, title = {Serial Fecal Microbiota Infusions via Colonoscopy for Active Ulcerative Colitis: A Feasibility, Safety, and Translational Monocentric Italian Study.}, journal = {Microorganisms}, volume = {11}, number = {10}, pages = {}, pmid = {37894194}, issn = {2076-2607}, abstract = {The effectiveness of fecal microbiota transplantation (FMT) in ulcerative colitis (UC) remains unclear. This study aimed to investigate the feasibility and effectiveness of serial fecal infusions via colonoscopy in patients with active UC. Subjects with mild-to-moderate UC received three consecutive fecal infusions via colonoscopy. A control population with the same baseline features receiving Infliximab treatment was enrolled. Adverse events and clinical, endoscopic, and microbial outcomes were investigated. Nineteen patients with mildly-to-moderately active UC were enrolled. Clinical response was obtained in six patients at week 2, in eight at week 6, and in nine at week 12. Clinical response was maintained in eight patients at week 24. Endoscopic remission at week 12 was reached in six patients. In the control population, 13/19 patients achieved clinical response at week 6, and 10/19 patients maintained clinical response after 6 months. Microbiota richness was higher in responders compared with the non-responders. Peptostreptococcus, Lactobacillus, and Veillonella were higher in non-responders, while Parabacteroides, Bacteroides, Faecalibacterium, and Akkermansia were higher in responders at all timepoints. Serial FMT infusions appear to be feasible, safe, and effective in UC patients, with a potential role in inducing and maintaining clinical response. Specific bacteria predict the response to FMT.}, }
@article {pmid37894167, year = {2023}, author = {Cláudia-Ferreira, A and Barbosa, DJ and Saegeman, V and Fernández-Rodríguez, A and Dinis-Oliveira, RJ and Freitas, AR and On Behalf Of The Escmid Study Group Of Forensic And Post-Mortem Microbiology Esgfor, }, title = {The Future Is Now: Unraveling the Expanding Potential of Human (Necro)Microbiome in Forensic Investigations.}, journal = {Microorganisms}, volume = {11}, number = {10}, pages = {}, pmid = {37894167}, issn = {2076-2607}, abstract = {The relevance of postmortem microbiological examinations has been controversial for decades, but the boom in advanced sequencing techniques over the last decade is increasingly demonstrating their usefulness, namely for the estimation of the postmortem interval. This comprehensive review aims to present the current knowledge about the human postmortem microbiome (the necrobiome), highlighting the main factors influencing this complex process and discussing the principal applications in the field of forensic sciences. Several limitations still hindering the implementation of forensic microbiology, such as small-scale studies, the lack of a universal/harmonized workflow for DNA extraction and sequencing technology, variability in the human microbiome, and limited access to human cadavers, are discussed. Future research in the field should focus on identifying stable biomarkers within the dominant Bacillota and Pseudomonadota phyla, which are prevalent during postmortem periods and for which standardization, method consolidation, and establishment of a forensic microbial bank are crucial for consistency and comparability. Given the complexity of identifying unique postmortem microbial signatures for robust databases, a promising future approach may involve deepening our understanding of specific bacterial species/strains that can serve as reliable postmortem interval indicators during the process of body decomposition. Microorganisms might have the potential to complement routine forensic tests in judicial processes, requiring robust investigations and machine-learning models to bridge knowledge gaps and adhere to Locard's principle of trace evidence.}, }
@article {pmid37884870, year = {2023}, author = {Mukherjee, P and Paul, S and Dutta, T and Nath, S and Ghosh, B and Chatterjee, D and Mukhopadhyay, S and Mukherjee, S}, title = {Nasal MRSA carriage is a risk factor for development of antibiotic resistance in diabetic foot ulcers and is significantly higher than diabetic and non-diabetic individuals without foot ulcer.}, journal = {BMC infectious diseases}, volume = {23}, number = {1}, pages = {729}, pmid = {37884870}, issn = {1471-2334}, support = {63 (Sanc.)-BT (Estt.)-RD-20/2016//Department of Biotechnology, Government of West Bengal/ ; 63 (Sanc.)-BT (Estt.)-RD-20/2016//Department of Biotechnology, Government of West Bengal/ ; }, mesh = {Humans ; *Diabetic Foot/drug therapy ; *Methicillin-Resistant Staphylococcus aureus ; Methicillin Resistance ; Staphylococcus aureus ; Risk Factors ; *Staphylococcal Infections/complications/drug therapy/microbiology ; Anti-Bacterial Agents/pharmacology/therapeutic use ; Multiplex Polymerase Chain Reaction ; *Diabetes Mellitus/drug therapy ; }, abstract = {BACKGROUND: Diabetic foot ulcer (DFU) is a major complication of diabetes often impacted by polymicrobial infection in the wound site. Diabetic patients are immunocompromised in nature and hence vulnerable to infection once the skin barrier is breached. Microbiological culture-based methods show that Staphylococcus aureus (SA) is the most frequently isolated bacteria from the DFU wounds. SA and its most clinically important antibiotic resistant variant methicillin-resistant S. aureus (MRSA) are commonly found in the nasal vestibule and colonization of SA as well as MRSA in any wound site can aggravate the condition. We hypothesize that the presence of nasal MRSA carriage can serve as a potential risk factor contributing to the emergence of antibiotic resistance in diabetic foot ulcer wounds.<br><br>METHODS: In the present study, we have compared the carriage of SA and MRSA in nasal cavity and foot skin among DFU patients (D+F+, n&#x2009;=&#x2009;50), diabetic patients without any ulcer (D+F-, n&#x2009;=&#x2009;50), and healthy controls (D-F-, n&#x2009;=&#x2009;40) by using bacterial culture and PCR based methods. The D+F+, D+F- and D-F-individuals were further categorized based on the presence or absence of MRSA and clinical parameters were compared between MRSA+&#x2009;ve and MRSA-ve individuals in each of the three groups mentioned above.<br><br>RESULTS: Our results show that, (a) nasal MRSA carriage is significantly higher (p&#x2009;<&#x2009;0.05) in D+F+&#x2009;group than the D+F- and D-F- and significantly associated with wound MRSA carriage in D+&#x2009;F+&#x2009;individuals (O.R.&#x2009;=&#x2009;4.09; 95% C.I.&#x2009;=&#x2009;1.12-15.05) and (b) the HbA1C level is significantly higher (p&#x2009;<&#x2009;0.02) in wound MRSA positive, compared to MRSA negative D+F+&#x2009;patients. Interestingly more than half of the MRSA (64%) isolated from DFU wound were identified to be multidrug resistant.<br><br>CONCLUSION: These findings strongly suggest that nasal MRSA carriage can act as a risk factor for development of antibiotic resistance in diabetic foot ulcers and it is therefore important to screen nasal and wound sites of these patients regularly. We have also developed a rapid multiplex PCR assay to detect MRSA from clinical isolates or microbial DNA isolated from clinical samples in the hospital settings.}, }
@article {pmid37884078, year = {2024}, author = {Steinbach, E and Masi, D and Ribeiro, A and Serradas, P and Le Roy, T and Clément, K}, title = {Upper small intestine microbiome in obesity and related metabolic disorders: A new field of investigation.}, journal = {Metabolism: clinical and experimental}, volume = {150}, number = {}, pages = {155712}, doi = {10.1016/j.metabol.2023.155712}, pmid = {37884078}, issn = {1532-8600}, mesh = {Humans ; *Diabetes Mellitus, Type 2 ; *Microbiota ; *Metabolic Diseases/metabolism ; Obesity/therapy ; Intestine, Small/metabolism ; }, abstract = {The study of the gut microbiome holds great promise for understanding and treating metabolic diseases, as its functions and derived metabolites can influence the metabolic status of the host. While research on the fecal microbiome has provided valuable insights, it tells us only part of the story. This limitation arises from the substantial variations in microorganism distribution throughout the gastrointestinal tract due to changes in physicochemical conditions. Thus, relying solely on the fecal microbiome may not be sufficient to draw comprehensive conclusions about metabolic diseases. The proximal part of the small intestine, particularly the jejunum, indeed, serves as the crucial site for digestion and absorption of nutrients, suggesting a potential role of its microbiome in metabolic regulation. Unfortunately, it remains relatively underexplored due to limited accessibility. This review presents current evidence regarding the relationships between the microbiome in the upper small intestine and various phenotypes, focusing on obesity and type 2 diabetes, in both humans and rodents. Research on humans is still limited with variability in the population and methods used. Accordingly, to better understand the role of the whole gut microbiome in metabolic diseases, studies exploring the human microbiome in different niches are needed.}, }
@article {pmid37883976, year = {2023}, author = {Blanco-Míguez, A and Gálvez, EJC and Pasolli, E and De Filippis, F and Amend, L and Huang, KD and Manghi, P and Lesker, TR and Riedel, T and Cova, L and Punčochář, M and Thomas, AM and Valles-Colomer, M and Schober, I and Hitch, TCA and Clavel, T and Berry, SE and Davies, R and Wolf, J and Spector, TD and Overmann, J and Tett, A and Ercolini, D and Segata, N and Strowig, T}, title = {Extension of the Segatella copri complex to 13 species with distinct large extrachromosomal elements and associations with host conditions.}, journal = {Cell host &amp; microbe}, volume = {31}, number = {11}, pages = {1804-1819.e9}, pmid = {37883976}, issn = {1934-6069}, support = {R01 CA230551/CA/NCI NIH HHS/United States ; U01 CA230551/CA/NCI NIH HHS/United States ; }, mesh = {Humans ; Male ; *Gastrointestinal Microbiome/genetics ; Metagenome ; *Microbiota ; Phylogeny ; Prevotella ; Female ; }, abstract = {The Segatella copri (formerly Prevotella copri) complex (ScC) comprises taxa that are key members of the human gut microbiome. It was previously described to contain four distinct phylogenetic clades. Combining targeted isolation with large-scale metagenomic analysis, we defined 13 distinct Segatella copri-related species, expanding the ScC complex beyond four clades. Complete genome reconstruction of thirteen strains from seven species unveiled the presence of genetically diverse large circular extrachromosomal elements. These elements are consistently present in most ScC species, contributing to intra- and inter-species diversities. The nine species-level clades present in humans display striking differences in prevalence and intra-species genetic makeup across human populations. Based on a meta-analysis, we found reproducible associations between members of ScC and the male sex and positive correlations with lower visceral fat and favorable markers of cardiometabolic health. Our work uncovers genomic diversity within ScC, facilitating a better characterization of the human microbiome.}, }
@article {pmid37882845, year = {2023}, author = {Om, H and Chand, U and Kushawaha, PK}, title = {Human anaerobic microbiome: a promising and innovative tool in cancer prevention and treatment by targeting pyruvate metabolism.}, journal = {Cancer immunology, immunotherapy : CII}, volume = {72}, number = {12}, pages = {3919-3930}, pmid = {37882845}, issn = {1432-0851}, mesh = {Humans ; Anaerobiosis ; *Microbiota ; *Neoplasms/prevention &amp; control ; Pyruvates ; Bacteria, Anaerobic ; }, abstract = {INTRODUCTION: Even in present-day times, cancer is one of the most fatal diseases. People are overwhelmed by pricey chemotherapy, immunotherapy, and other costly cancer therapies in poor and middle-income countries. Cancer cells grow under anaerobic and hypoxic conditions. Pyruvate is the final product of the anaerobic glycolysis pathway, and many cancer cells utilize pyruvate for their growth and development. The anaerobic microbiome produces many anti-cancer substances that can act as anti-tumor agents and are both feasible and of low cost. There are different mechanisms of action of the anaerobic microbiome, such as the production of short-chain fatty acids (SCFAs), and competition for the anaerobic environment includes the metabolic product pyruvate to form lactic acid for energy.<br><br>KEY FINDINGS: In this review, we have summarized the role of the metabolic approach of the anaerobic human microbiome in cancer prevention and treatment by interfering with cancer metabolite pyruvate. SCFAs possess decisive outcomes in condoning almost all the hallmarks of cancer and helping the spread of cancer to other body parts. Studies have demonstrated the impact and significance of using SCFA, which results from anaerobic bacteria, as an anti-cancer agent. Anaerobic bacteria-based cancer therapy has become a promising approach to treat cancer using obligate and facultative anaerobic bacteria because of their ability to penetrate and increase in an acidic hypoxic environment.<br><br>SIGNIFICANCE: This review attempts to provide the interconnection of cancer metabolism and anaerobic microbiome metabolism with a focus on pyruvate metabolism to understand and design unique anaerobic microbiota-based therapy for cancer patients.}, }
@article {pmid37882794, year = {2023}, author = {Väinämö, S and Saqib, S and Kalliala, I and Kervinen, K and Luiro, K and Niinimäki, M and Halttunen-Nieminen, M and Virtanen, S and Nieminen, P and Salonen, A and Holster, T}, title = {Longitudinal analysis of vaginal microbiota during IVF fresh embryo transfer and in early pregnancy.}, journal = {Microbiology spectrum}, volume = {11}, number = {6}, pages = {e0165023}, pmid = {37882794}, issn = {2165-0497}, support = {814102//EC | H2020 | PRIORITY 'Excellent science' | H2020 Marie Sk&#x142;odowska-Curie Actions (MSCA)/ ; TYH2020401//Department of Obstetrics and Gynaecology, Helsinki University Hospital/ ; //Suomen L&#xe4;&#xe4;ketieteen S&#xe4;&#xe4;ti&#xf6; (Finnish Medical Foundation)/ ; //Academy of Finland (AKA)/ ; }, mesh = {Pregnancy ; Female ; Humans ; Embryo Transfer ; Fertilization in Vitro ; *Infertility/therapy ; Vagina ; *Microbiota ; }, abstract = {Infertility is a global public health issue which leads many couples to seek fertility treatments, of which in vitro fertilization (IVF) is considered to be the most effective. Still, only about one-third of the women achieve live birth after the first IVF embryo transfer (IVF-ET). Factors affecting embryo implantation are poorly known, but the female reproductive tract microbiota may play a key role. Our study confirms the beneficial role of vaginal lactobacilli, especially Lactobacillus crispatus, in the probability of achieving clinical pregnancy and live birth following IVF-ET. Our findings regarding the intra-individual shift of vaginal microbiota between non-pregnancy and pregnancy states are novel and provide new information about the dynamics of microbiota in the early steps of human reproduction. These findings may help clinicians in their attempts to optimize the conditions for ET by microbiota screening or modulation and timing the ET when the microbiota is the most favorable.}, }
@article {pmid37881747, year = {2023}, author = {Sampaio, S and Araujo, R and Merino-Riba, A and Lelouvier, B and Servant, F and Quelhas-Santos, J and Pestana, M and Sampaio-Maia, B}, title = {Blood, Gut, and Oral Microbiome in Kidney Transplant Recipients.}, journal = {Indian journal of nephrology}, volume = {33}, number = {5}, pages = {366-370}, pmid = {37881747}, issn = {0971-4065}, abstract = {BACKGROUND AND OBJECTIVE: Recent reports describe the existence of a blood microbiome profile not associated with an infection state. Given the high impact that the dysbiotic human microbiome appears to have in chronic kidney disease and, in particular, in the outcome of kidney transplant recipients (KTRs), we aimed to explore the variations and correlations of the gut, oral, and blood microbiome of recipients, 3 months after kidney transplantation.<br><br>MATERIALS AND METHODS: We conducted a cross-sectional study where the microbiome of stool, saliva, and blood collected from recipients 3 months after kidney transplantation (N = 6) was analyzed by polymerase chain reaction (PCR) amplification and sequencing of the V3-V4 hypervariable regions of the 16S rRNA gene using MiSeq Illumina[&#xae;] technology.<br><br>RESULTS: Blood of KTRs harbors a distinct low-abundance microbiome dominated by Proteobacteria and Firmicutes. Gut and oral microbiome of KTRs also present distinct profiles. The existence of a proportion of shared operational taxonomic units among the different body sites is reported, mainly classified as Proteobacteria and Firmicutes.<br><br>CONCLUSIONS: This study provides evidence of existence a blood microbiome in KTRs, different from the gut and the oral microbiome profiles, with a small number of operational taxonomic units representing a shared microbiome. The clinical relevance of this observation should be further explored in these patients.}, }
@article {pmid37875417, year = {2024}, author = {Li, J and Yang, Z and Yuan, W and Bao, Z and Li, MD}, title = {Heme Metabolism Mediates the Effects of Smoking on Gut Microbiome.}, journal = {Nicotine &amp; tobacco research : official journal of the Society for Research on Nicotine and Tobacco}, volume = {26}, number = {6}, pages = {742-751}, doi = {10.1093/ntr/ntad209}, pmid = {37875417}, issn = {1469-994X}, support = {2016YFC0906300//China Precision Medicine Initiative/ ; 2021539200340045//Joint Research Institute of Tobacco and Health of China/ ; //Research Center for Air Pollution and Health of Zhejiang University/ ; }, mesh = {Humans ; *Gastrointestinal Microbiome ; *Heme/metabolism ; Transcriptome ; Male ; Female ; Metagenome ; Adult ; Smoking/adverse effects ; Bacteroides/genetics ; }, abstract = {INTRODUCTION: The number of smokers worldwide increased greatly during the past decades and reached 1.14 billion in 2019, becoming a leading risk factor for human health. Tobacco smoking has wide effects on human genetics, epigenetics, transcriptome, and gut microbiome. Although many studies have revealed effects of smoking on host transcriptome, research on the relationship between smoking, host gene expression, and the gut microbiome is limited.<br><br>AIMS AND METHODS: We first explored transcriptome and metagenome profile differences between smokers and nonsmokers. To evaluate the relationship between host gene expression and gut microbiome, we then applied bidirectional mediation analysis to infer causal relationships between smoking, gene expression, and gut microbes.<br><br>RESULTS: Metagenome and transcriptome analyses revealed 71 differential species and 324 differential expressed genes between smokers and nonsmokers. With smoking as an exposure variable, we identified 272 significant causal relationships between gene expression and gut microbes, among which there were 247 genes that mediate the effect of smoking on gut microbes. Pathway-based enrichment analysis showed that these genes were significantly enriched in heme metabolic pathway, which mainly mediated the changes of Bacteroides finegoldii and Lachnospiraceae bacterium 9_1_43BFAA. Additionally, by performing metabolome data analysis in the Integrated Human Microbiome Project (iHMP) database, we verified the correlation between the intermediate products of the heme metabolism pathway (porphobilinogen, bilirubin, and biliverdin) and gut microbiome.<br><br>CONCLUSIONS: By investigating the bidirectional interaction between smoking-related host gene expression and gut microbes, this study provided evidence for the mediation of smoking on gut microbes through co-involvement or interaction of heme metabolism.<br><br>IMPLICATIONS: By comparing the metagenome and transcriptome sequencing profiles between 34 smokers and 33 age- and gender-matched nonsmokers, we are the first to reveal causal relationships among tobacco smoking, host gene expression, and gut microbes. These findings offer insight into how smoking affects gut microbes through host gene expression and metabolism, which highlights the importance of heme metabolism in modulating the effects of smoking on gut microbiome.}, }
@article {pmid37874156, year = {2023}, author = {Vänni, P and Tejesvi, MV and Paalanne, N and Aagaard, K and Ackermann, G and Camargo, CA and Eggesbø, M and Hasegawa, K and Hoen, AG and Karagas, MR and Kolho, K-L and Laursen, MF and Ludvigsson, J and Madan, J and Ownby, D and Stanton, C and Stokholm, J and Tapiainen, T}, title = {Machine-learning analysis of cross-study samples according to the gut microbiome in 12 infant cohorts.}, journal = {mSystems}, volume = {8}, number = {6}, pages = {e0036423}, pmid = {37874156}, issn = {2379-5077}, support = {UH3 OD023275/OD/NIH HHS/United States ; UH3 OD023253/OD/NIH HHS/United States ; UG3 OD023275/OD/NIH HHS/United States ; UG3 OD023253/OD/NIH HHS/United States ; R01 LM012723/LM/NLM NIH HHS/United States ; R01 HD091731/HD/NICHD NIH HHS/United States ; R01 DK089201/DK/NIDDK NIH HHS/United States ; }, mesh = {Infant ; Humans ; *Gastrointestinal Microbiome/genetics ; Feces ; *Microbiota ; Machine Learning ; RNA, Ribosomal, 16S/genetics ; }, abstract = {There are challenges in merging microbiome data from diverse research groups due to the intricate and multifaceted nature of such data. To address this, we utilized a combination of machine-learning (ML) models to analyze 16S sequencing data from a substantial set of gut microbiome samples, sourced from 12 distinct infant cohorts that were gathered prospectively. Our initial focus was on the mode of delivery due to its prior association with changes in infant gut microbiomes. Through ML analysis, we demonstrated the effective merging and comparison of various gut microbiome data sets, facilitating the identification of robust microbiome biomarkers applicable across varied study populations.}, }
@article {pmid37873416, year = {2023}, author = {Abdill, RJ and Graham, SP and Rubinetti, V and Albert, FW and Greene, CS and Davis, S and Blekhman, R}, title = {Integration of 168,000 samples reveals global patterns of the human gut microbiome.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {37873416}, issn = {2692-8205}, support = {P30 DK042086/DK/NIDDK NIH HHS/United States ; R01 LM013863/LM/NLM NIH HHS/United States ; }, abstract = {Understanding the factors that shape variation in the human microbiome is a major goal of research in biology. While other genomics fields have used large, pre-compiled compendia to extract systematic insights requiring otherwise impractical sample sizes, there has been no comparable resource for the 16S rRNA sequencing data commonly used to quantify microbiome composition. To help close this gap, we have assembled a set of 168,484 publicly available human gut microbiome samples, processed with a single pipeline and combined into the largest unified microbiome dataset to date. We use this resource, which is freely available at microbiomap.org, to shed light on global variation in the human gut microbiome. We find that Firmicutes, particularly Bacilli and Clostridia, are almost universally present in the human gut. At the same time, the relative abundance of the 65 most common microbial genera differ between at least two world regions. We also show that gut microbiomes in undersampled world regions, such as Central and Southern Asia, differ significantly from the more thoroughly characterized microbiomes of Europe and Northern America. Moreover, humans in these overlooked regions likely harbor hundreds of taxa that have not yet been discovered due to this undersampling, highlighting the need for diversity in microbiome studies. We anticipate that this new compendium can serve the community and enable advanced applied and methodological research.}, }
@article {pmid37873282, year = {2023}, author = {Anderson, DM and Logan, MG and Patty, SS and Kendall, AJ and Borland, CZ and Pfeifer, CS and Kreth, J and Merritt, JL}, title = {Microbiome imaging goes à la carte: Incorporating click chemistry into the fluorescence-activating and absorption-shifting tag (FAST) imaging platform.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {37873282}, issn = {2692-8205}, support = {R01 DE029492/DE/NIDCR NIH HHS/United States ; R21 DE029612/DE/NIDCR NIH HHS/United States ; R35 DE028252/DE/NIDCR NIH HHS/United States ; R35 DE029083/DE/NIDCR NIH HHS/United States ; }, abstract = {The human microbiome is predominantly composed of facultative and obligate anaerobic bacteria that live in hypoxic/anoxic polymicrobial biofilm communities. Given the oxidative sensitivity of large fractions of the human microbiota, green fluorescent protein (GFP) and related genetically-encoded fluorophores only offer limited utility for live cell imaging due the oxygen requirement for chromophore maturation. Consequently, new fluorescent imaging modalities are needed to study polymicrobial interactions and microbiome-host interactions within anaerobic environments. The fluorescence-activating and absorption shifting tag (FAST) is a rapidly developing genetically-encoded fluorescent imaging technology that exhibits tremendous potential to address this need. In the FAST system, fluorescence only occurs when the FAST protein is complexed with one of a suite of cognate small molecule fluorogens. To expand the utility of FAST imaging, we sought to develop a modular platform (Click-FAST) to democratize fluorogen engineering for personalized use cases. Using Click-FAST, investigators can quickly and affordably sample a vast chemical space of compounds, potentially imparting a broad range of desired functionalities to the parental fluorogen. In this work, we demonstrate the utility of the Click-FAST platform using a novel fluorogen, [PL]Blaze-alkyne, which incorporates the widely available small molecule ethylvanillin as the hydroxybenzylidine head group. Different azido reagents were clicked onto [PL]Blaze-alkyne and shown to impart useful characteristics to the fluorogen, such as selective bacterial labeling in mixed populations as well as fluorescent signal enhancement. Conjugation of an 80 Å PEG molecule to [PL]Blaze-alkyne illustrates the broad size range of functional fluorogen chimeras that can be employed. This PEGylated fluorogen also functions as an exquisitely selective membrane permeability marker capable of outperforming propidium iodide as a fluorescent marker of cell viability.}, }
@article {pmid37870467, year = {2024}, author = {Wang, M and Liu, G and Liu, M and Tai, C and Deng, Z and Song, J and Ou, HY}, title = {ICEberg 3.0: functional categorization and analysis of the integrative and conjugative elements in bacteria.}, journal = {Nucleic acids research}, volume = {52}, number = {D1}, pages = {D732-D737}, pmid = {37870467}, issn = {1362-4962}, support = {32070572//National Natural Science Foundation of China/ ; 19JC1413000//Science and Technology Commission of Shanghai Municipality/ ; }, mesh = {Humans ; *Bacteria/genetics ; *Conjugation, Genetic ; Databases, Factual ; *Databases, Genetic ; DNA Transposable Elements ; Microbiota ; }, abstract = {ICEberg 3.0 (https://tool2-mml.sjtu.edu.cn/ICEberg3/) is an upgraded database that provides comprehensive insights into bacterial integrative and conjugative elements (ICEs). In comparison to the previous version, three key enhancements were introduced: First, through text mining and manual curation, it now encompasses details of 2065 ICEs, 607 IMEs and 275 CIMEs, including 430 with experimental support. Secondly, ICEberg 3.0 systematically categorizes cargo gene functions of ICEs into six groups based on literature curation and predictive analysis, providing a profound understanding of ICEs'diverse biological traits. The cargo gene prediction pipeline is integrated into the online tool ICEfinder 2.0. Finally, ICEberg 3.0 aids the analysis and exploration of ICEs from the human microbiome. Extracted and manually curated from 2405 distinct human microbiome samples, the database comprises 1386 putative ICEs, offering insights into the complex dynamics of Bacteria-ICE-Cargo networks within the human microbiome. With the recent updates, ICEberg 3.0 enhances its capability to unravel the intricacies of ICE biology, particularly in the characterization and understanding of cargo gene functions and ICE interactions within the microbiome. This enhancement may facilitate the investigation of the dynamic landscape of ICE biology and its implications for microbial communities.}, }
@article {pmid37869650, year = {2023}, author = {Ibrahimi, E and Lopes, MB and Dhamo, X and Simeon, A and Shigdel, R and Hron, K and Stres, B and D'Elia, D and Berland, M and Marcos-Zambrano, LJ}, title = {Overview of data preprocessing for machine learning applications in human microbiome research.}, journal = {Frontiers in microbiology}, volume = {14}, number = {}, pages = {1250909}, pmid = {37869650}, issn = {1664-302X}, abstract = {Although metagenomic sequencing is now the preferred technique to study microbiome-host interactions, analyzing and interpreting microbiome sequencing data presents challenges primarily attributed to the statistical specificities of the data (e.g., sparse, over-dispersed, compositional, inter-variable dependency). This mini review explores preprocessing and transformation methods applied in recent human microbiome studies to address microbiome data analysis challenges. Our results indicate a limited adoption of transformation methods targeting the statistical characteristics of microbiome sequencing data. Instead, there is a prevalent usage of relative and normalization-based transformations that do not specifically account for the specific attributes of microbiome data. The information on preprocessing and transformations applied to the data before analysis was incomplete or missing in many publications, leading to reproducibility concerns, comparability issues, and questionable results. We hope this mini review will provide researchers and newcomers to the field of human microbiome research with an up-to-date point of reference for various data transformation tools and assist them in choosing the most suitable transformation method based on their research questions, objectives, and data characteristics.}, }
@article {pmid37864136, year = {2023}, author = {Tan, A and Murugapiran, S and Mikalauskas, A and Koble, J and Kennedy, D and Hyde, F and Ruotti, V and Law, E and Jensen, J and Schroth, GP and Macklaim, JM and Kuersten, S and LeFrançois, B and Gohl, DM}, title = {Rational probe design for efficient rRNA depletion and improved metatranscriptomic analysis of human microbiomes.}, journal = {BMC microbiology}, volume = {23}, number = {1}, pages = {299}, pmid = {37864136}, issn = {1471-2180}, mesh = {Humans ; RNA, Ribosomal/genetics ; Bacteria/genetics ; RNA, Ribosomal, 16S/genetics ; *Microbiota/genetics ; *Gastrointestinal Microbiome/genetics ; }, abstract = {The microbiota that colonize the human gut and other tissues are dynamic, varying both in composition and functional state between individuals and over time. Gene expression measurements can provide insights into microbiome composition and function. However, efficient and unbiased removal of microbial ribosomal RNA (rRNA) presents a barrier to acquiring metatranscriptomic data. Here we describe a probe set that achieves efficient enzymatic rRNA removal of complex human-associated microbial communities. We demonstrate that the custom probe set can be further refined through an iterative design process to efficiently deplete rRNA from a range of human microbiome samples. Using synthetic nucleic acid spike-ins, we show that the rRNA depletion process does not introduce substantial quantitative error in gene expression profiles. Successful rRNA depletion allows for efficient characterization of taxonomic and functional profiles, including during the development of the human gut microbiome. The pan-human microbiome enzymatic rRNA depletion probes described here provide a powerful tool for studying the transcriptional dynamics and function of the human microbiome.}, }
@article {pmid37863831, year = {2024}, author = {Budzinski, L and von Goetze, V and Chang, HD}, title = {Single-cell phenotyping of bacteria combined with deep sequencing for improved contextualization of microbiome analyses.}, journal = {European journal of immunology}, volume = {54}, number = {1}, pages = {e2250337}, doi = {10.1002/eji.202250337}, pmid = {37863831}, issn = {1521-4141}, support = {375876048 TRR241 B03//Deutsche Forschungsgemeinschaft/ ; CH938/4-1//Deutsche Forschungsgemeinschaft/ ; 1.6./01: "BacFlow - Analyse bakterieller Gemeinschaften durch Mikrobiota-Zytometrie."//EFRE-Projekt/ ; }, mesh = {Humans ; Cross-Sectional Studies ; *Microbiota ; Bacteria/genetics ; Flow Cytometry ; High-Throughput Nucleotide Sequencing ; }, abstract = {Great effort was made to characterize the bacterial communities inhabiting the human body as a factor in disease, resulting in the realization that a wide spectrum of diseases is associated with an altered composition of the microbiome. However, the identification of disease-relevant bacteria has been hindered by the high cross-sectional diversity of individual microbiomes, and in most cases, it remains unclear whether the observed alterations are cause or consequence of disease. Hence, innovative analysis approaches are required that enable inquiries of the microbiome beyond mere taxonomic cataloging. This review highlights the utility of microbiota flow cytometry, a single-cell analysis platform to directly interrogate cellular interactions, cell conditions, and crosstalk with the host's immune system within the microbiome to take into consideration the role of microbes as critical interaction partners of the host and the spectrum of microbiome alterations, beyond compositional changes. In conjunction with advanced sequencing approaches it could reveal the genetic potential of target bacteria and advance our understanding of taxonomic diversity and gene usage in the context of the microenvironment. Single-cell bacterial phenotyping has the potential to change our perspective on the human microbiome and empower microbiome research for the development of microbiome-based therapy approaches and personalized medicine.}, }
@article {pmid37851822, year = {2023}, author = {Farias Amorim, C and Lovins, VM and Singh, TP and Novais, FO and Harris, JC and Lago, AS and Carvalho, LP and Carvalho, EM and Beiting, DP and Scott, P and Grice, EA}, title = {Multiomic profiling of cutaneous leishmaniasis infections reveals microbiota-driven mechanisms underlying disease severity.}, journal = {Science translational medicine}, volume = {15}, number = {718}, pages = {eadh1469}, pmid = {37851822}, issn = {1946-6242}, support = {F31 AR079845/AR/NIAMS NIH HHS/United States ; P50 AI030639/AI/NIAID NIH HHS/United States ; P30 AR069589/AR/NIAMS NIH HHS/United States ; R01 NR015639/NR/NINR NIH HHS/United States ; T32 AR007465/AR/NIAMS NIH HHS/United States ; F31 AR079901/AR/NIAMS NIH HHS/United States ; R01 AI162711/AI/NIAID NIH HHS/United States ; R01 AI143790/AI/NIAID NIH HHS/United States ; }, mesh = {Humans ; Mice ; Animals ; Staphylococcus aureus ; Multiomics ; *Leishmaniasis, Cutaneous ; Inflammation ; Bacteria ; *Microbiota ; Patient Acuity ; }, abstract = {Leishmania braziliensis is a parasitic infection that can result in inflammation and skin injury with highly variable and unpredictable clinical outcomes. Here, we investigated the potential impact of microbiota on infection-induced inflammatory responses and disease resolution by conducting an integrated analysis of the skin microbiome and host transcriptome on a cohort of 62 patients infected with L. braziliensis. We found that overall bacterial burden and microbiome configurations dominated with Staphylococcus spp. were associated with delayed healing and enhanced inflammatory responses, especially by IL-1 family members. Quantification of host and bacterial transcripts on human lesions revealed that high lesional S. aureus transcript abundance was associated with delayed healing and increased expression of IL-1β. This cytokine was critical for modulating disease outcomes in L. braziliensis-infected mice colonized with S. aureus, given that its neutralization reduced pathology and inflammation. These results highlight how the human microbiome can shape disease outcomes in cutaneous leishmaniasis and suggest pathways toward host-directed therapies to mitigate the inflammatory consequences.}, }
@article {pmid37847418, year = {2023}, author = {Refisch, A and Walter, M}, title = {[The importance of the human microbiome for mental health].}, journal = {Der Nervenarzt}, volume = {94}, number = {11}, pages = {1001-1009}, pmid = {37847418}, issn = {1433-0407}, mesh = {Humans ; Mental Health ; *Gastrointestinal Microbiome/physiology ; *Microbiota ; *Mental Disorders/therapy ; Brain ; }, abstract = {Many common diseases including psychiatric disorders show characteristic alterations in the microbiome. Preclinical studies have uncovered important mechanisms by which the microbiome interacts bidirectionally with neural functions. Dysregulation of the complex interplay between the microbiome, immune system, stress response, and energy homeostasis, particularly in the early stages of life, can predispose to the development of psychiatric symptoms later in life. Although few clinical studies are available to date, the broad influence of the microbiome on neural and mental functions as well as its high plasticity, have generated great interest in its therapeutic potential for common psychiatric disorders.}, }
@article {pmid37846925, year = {2023}, author = {Sun, L and Wang, Q and Wang, H and Huang, J and Yu, Z}, title = {A cross-sectional cohort study on the skin microbiota in patients with different acne durations.}, journal = {Experimental dermatology}, volume = {32}, number = {12}, pages = {2102-2111}, doi = {10.1111/exd.14951}, pmid = {37846925}, issn = {1600-0625}, support = {32000054//National Natural Science Foundation of China/ ; 32170071//National Natural Science Foundation of China/ ; }, mesh = {Humans ; RNA, Ribosomal, 16S/genetics ; Cross-Sectional Studies ; *Acne Vulgaris/microbiology ; Skin/microbiology ; *Microbiota/genetics ; Cohort Studies ; }, abstract = {Acne is a chronic disease that often persists for years. Skin microbial communities play an essential role in the development of acne. However, limited information is available about the dynamic patterns of skin microbiota in acne. This study aimed to characterize microbial community changes in skin pores and surfaces of acne patients with varying disease time. In this study, a total of 70 skin samples from 22 subjects were collected and sequenced using 16S rRNA amplicon sequencing. Although microbial compositions in skin pores were similar over time, significant differences in microbial structure were observed on the skin surface, with the dominance of Cutibacterium in the first 3 years and replacement by Staphylococcus in 4-6 years. Lactobacillus and Acinetobacter were more abundant in the normal group and continuingly decreased with disease time on the skin surface. Microbial networks further revealed substantial increases in microbial interactions in the 4-6 years group in both skin surfaces and pores. These results demonstrate that the skin microbiota alters with the disease duration and may provide a potential guide in redirecting skin microbiota towards healthy states.}, }
@article {pmid37843778, year = {2024}, author = {Shad, NS and Shaikh, NI and Cunningham, SA}, title = {Migration Spurs Changes in the Human Microbiome: a Review.}, journal = {Journal of racial and ethnic health disparities}, volume = {11}, number = {6}, pages = {3618-3632}, pmid = {37843778}, issn = {2196-8837}, support = {R25DK078381/DK/NIDDK NIH HHS/United States ; R25DK078381/DK/NIDDK NIH HHS/United States ; }, mesh = {Humans ; *Microbiota ; Emigration and Immigration/statistics &amp; numerical data ; Emigrants and Immigrants/statistics &amp; numerical data ; }, abstract = {International migration often results in major changes in living environments and lifestyles, and these changes may lead to the observed increases in obesity and diabetes among foreign-born people after resettling in higher-income countries. A possible mechanism linking changes in living environments to the onset of health conditions may be changes in the microbiome. Previous research has shown that unfavorable changes in the composition of the microbiome can increase disposition to diseases such as diabetes, obesity, kidney disease, and inflammatory bowel disease. We investigated the relationship between human migration and microbiome composition through a review using microbiome- and migration-related search terms in PubMed and Web of Science. We included articles examining the gut, oral, or oropharyngeal microbiome in people who migrated internationally. Nine articles met eligibility criteria. All but one examined migration from a non-Western to a Western country. Four of these found a difference in the microbiome of migrants compared with non-migrating residents of their country of birth, seven found differences in the microbiome of migrants compared with the native-born population in the country of resettlement, and five found microbiome differences associated with duration of stay in the country of resettlement. Microbiome composition varies with country of birth, age at migration, time since immigration, and country of resettlement. The results suggest that migration may lead to changes in the microbiome; thus, microbiome characteristics are a plausible pathway to examine changes in health after resettlement in a new country.}, }
@article {pmid37843744, year = {2024}, author = {Moitas, B and Caldas, IM and Sampaio-Maia, B}, title = {Microbiology and postmortem interval: a systematic review.}, journal = {Forensic science, medicine, and pathology}, volume = {20}, number = {2}, pages = {696-715}, pmid = {37843744}, issn = {1556-2891}, support = {(UIDB/04004/2020)//Minist&#xe9;rio da Ci&#xea;ncia, Tecnologia e Ensino Superior/ ; }, mesh = {Humans ; *Postmortem Changes ; *Microbiota ; }, abstract = {This systematic review aims to learn if and how it is possible to use the human microbiome to indicate the time elapsed after death. Articles were searched on the PubMed database using predefined data fields and keywords; reviews, systematic reviews, and meta-analyses were excluded. The final selection included 14 papers (out of 144). The results indicated that the microorganisms present in the cadaveric island succeed predictably over time, with markers between the stages of decomposition constituting a potential innovative tool for postmortem interval (PMI) estimation. The human microbiome has the potential to be used for PMI estimation and may present advantages as microbes are present in all seasons, in all habitats, including the most extreme ones, and because microbial communities respond predictably to environmental changes.}, }
@article {pmid37841330, year = {2023}, author = {Zhou, R and Ng, SK and Sung, JJY and Goh, WWB and Wong, SH}, title = {Data pre-processing for analyzing microbiome data - A mini review.}, journal = {Computational and structural biotechnology journal}, volume = {21}, number = {}, pages = {4804-4815}, pmid = {37841330}, issn = {2001-0370}, abstract = {The human microbiome is an emerging research frontier due to its profound impacts on health. High-throughput microbiome sequencing enables studying microbial communities but suffers from analytical challenges. In particular, the lack of dedicated preprocessing methods to improve data quality impedes effective minimization of biases prior to downstream analysis. This review aims to address this gap by providing a comprehensive overview of preprocessing techniques relevant to microbiome research. We outline a typical workflow for microbiome data analysis. Preprocessing methods discussed include quality filtering, batch effect correction, imputation of missing values, normalization, and data transformation. We highlight strengths and limitations of each technique to serve as a practical guide for researchers and identify areas needing further methodological development. Establishing robust, standardized preprocessing will be essential for drawing valid biological conclusions from microbiome studies.}, }
@article {pmid37840574, year = {2023}, author = {Jang, H and Park, S and Koh, H}, title = {Comprehensive microbiome causal mediation analysis using MiMed on user-friendly web interfaces.}, journal = {Biology methods &amp; protocols}, volume = {8}, number = {1}, pages = {bpad023}, pmid = {37840574}, issn = {2396-8923}, abstract = {It is a central goal of human microbiome studies to see the roles of the microbiome as a mediator that transmits environmental, behavioral, or medical exposures to health or disease outcomes. Yet, mediation analysis is not used as much as it should be. One reason is because of the lack of carefully planned routines, compilers, and automated computing systems for microbiome mediation analysis (MiMed) to perform a series of data processing, diversity calculation, data normalization, downstream data analysis, and visualizations. Many researchers in various disciplines (e.g. clinicians, public health practitioners, and biologists) are not also familiar with related statistical methods and programming languages on command-line interfaces. Thus, in this article, we introduce a web cloud computing platform, named as MiMed, that enables comprehensive MiMed on user-friendly web interfaces. The main features of MiMed are as follows. First, MiMed can survey the microbiome in various spheres (i) as a whole microbial ecosystem using different ecological measures (e.g. alpha- and beta-diversity indices) or (ii) as individual microbial taxa (e.g. phyla, classes, orders, families, genera, and species) using different data normalization methods. Second, MiMed enables covariate-adjusted analysis to control for potential confounding factors (e.g. age and gender), which is essential to enhance the causality of the results, especially for observational studies. Third, MiMed enables a breadth of statistical inferences in both mediation effect estimation and significance testing. Fourth, MiMed provides flexible and easy-to-use data processing and analytic modules and creates nice graphical representations. Finally, MiMed employs ChatGPT to search for what has been known about the microbial taxa that are found significantly as mediators using artificial intelligence technologies. For demonstration purposes, we applied MiMed to the study on the mediating roles of oral microbiome in subgingival niches between e-cigarette smoking and gingival inflammation. MiMed is freely available on our web server (http://mimed.micloud.kr).}, }
@article {pmid37839408, year = {2023}, author = {Frey-Furtado, L and Magalhães, I and Sampaio-Maia, B and Azevedo, MJ}, title = {Oral microbiome characterization in oral mucositis patients-A systematic review.}, journal = {Journal of oral pathology &amp; medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology}, volume = {52}, number = {10}, pages = {911-918}, doi = {10.1111/jop.13492}, pmid = {37839408}, issn = {1600-0714}, support = {SFRH/BD/144982/2019//Funda&#xe7;&#xe3;o para a Ci&#xea;ncia e a Tecnologia/ ; }, mesh = {Humans ; *Stomatitis ; *Microbiota ; *Drug-Related Side Effects and Adverse Reactions ; Candida ; Disease Progression ; }, abstract = {BACKGROUND: Oral mucositis (OM) is a severe and common adverse effect of cancer treatment. The oral microbiome appears to play a role on the onset and severity of OM. Therefore, this systematic review aims to characterize the oral dysbiosis associated with OM.<br><br>METHODS: The PRISMA checklist was followed and PubMed, Web of Science, and Scopus were screened for clinical studies characterizing the oral microbiome alterations in patients with OM.<br><br>RESULTS: From a total of 2500 articles retrieved, we included nine articles in this systematic review. Certain types of bacteria, as Fusobacterium, were recognized as predictors of the onset of OM. In addition, it was reported that patients with severe OM presented a reduction in alpha-diversity, an increase in beta-diversity. The abundance of some taxa significantly changed with OM severity, with Bacillota phylum and genera Leptotrichia, Actinomyces, and Prevotella decreasing and Treponema increasing with disease progression. Additionally, during cancer treatment, changes in the oral microbiome have been observed in OM patients, with an increase in Candida and nosocomial pathogens, including Staphylococcus species.<br><br>CONCLUSION: Our review indicates that cancer treatment can significantly alter the oral microbiome, with more pronounced changes observed in patients with severe OM in all relevant oral phyla, but more pronounced in Bacillota phylum.}, }
@article {pmid37835899, year = {2023}, author = {Man, MA and Ungur, RA and Motoc, NS and Pop, LA and Berindan-Neagoe, I and Ruta, VM}, title = {Lung Microbiota in Idiopathic Pulmonary Fibrosis, Hypersensitivity Pneumonitis, and Unclassified Interstitial Lung Diseases: A Preliminary Pilot Study.}, journal = {Diagnostics (Basel, Switzerland)}, volume = {13}, number = {19}, pages = {}, pmid = {37835899}, issn = {2075-4418}, abstract = {(1) Introduction: Although historically, the lung has been considered a sterile organ, recent studies through 16S rRNA gene sequencing have identified a substantial number of microorganisms. The human microbiome has been considered an "essential organ," carrying about 150 times more information (genes) than are found in the entire human genome. The purpose of the present study is to characterize and compare the microbiome in three different interstitial lung diseases: idiopathic pulmonary fibrosis (IPF), hypersensitivity pneumonitis, and nondifferential interstitial lung disease. (2) Material and methods: This was a prospective cohort study where the DNA of 28 patients with ILD was extracted from the lavage and then processed using the standard technique of 16S RNA gene sequencing. In a tertiary teaching hospital in the northern, western part of Romania, samples were collected through bronchoscopy and then processed. (3) Results: The same four species were found in all the patients but in different quantities and compositions: Firmicutes, Actinobacteria, Proteobacteria and Bacteroides. Streptococcus was the most prevalent genus, followed by Staphylococcus and Prevotella. Statistically significant differences in the OUT count for the ten most abundant taxa were found for the genus: Gemella, Actinobacteria, Prevotella, Neisseria, Haemophilus, and Bifidobacterium. The comparative analysis showed a richer microbiota in patients with IPF, as shown by the alpha diversity index. (4) Conclusions: In interstitial lung diseases, the microorganisms normally found in the lung are reduced to a restricted flora dominated by the Firmicutes family. These changes significantly disrupt the continuity of the observed bacterial pattern from the oropharynx to the bronchial tree and lung, possibly impacting the evolution and severity of interstitial lung diseases.}, }
@article {pmid37834423, year = {2023}, author = {Mascellino, MT}, title = {Molecular Research in Human Microbiome.}, journal = {International journal of molecular sciences}, volume = {24}, number = {19}, pages = {}, pmid = {37834423}, issn = {1422-0067}, mesh = {Humans ; *Gastrointestinal Microbiome ; Intestines ; Inflammation ; }, abstract = {Recent evidence has shown that the human microbiome is associated with a wide range of diseases, from non-neoplastic to tumourigenesis, including cancer, inflammation, intestinal damage, etc [...].}, }
@article {pmid37833788, year = {2023}, author = {Ma, C and Yang, C and Peng, A and Sun, T and Ji, X and Mi, J and Wei, L and Shen, S and Feng, Q}, title = {Pan-cancer spatially resolved single-cell analysis reveals the crosstalk between cancer-associated fibroblasts and tumor microenvironment.}, journal = {Molecular cancer}, volume = {22}, number = {1}, pages = {170}, pmid = {37833788}, issn = {1476-4598}, mesh = {Humans ; *Cancer-Associated Fibroblasts/metabolism ; Tumor Microenvironment ; *Carcinoma/metabolism ; Epithelial-Mesenchymal Transition/genetics ; Single-Cell Analysis ; Fibroblasts ; }, abstract = {Cancer-associated fibroblasts (CAFs) are a heterogeneous cell population that plays a crucial role in remodeling the tumor microenvironment (TME). Here, through the integrated analysis of spatial and single-cell transcriptomics data across six common cancer types, we identified four distinct functional subgroups of CAFs and described their spatial distribution characteristics. Additionally, the analysis of single-cell RNA sequencing (scRNA-seq) data from three additional common cancer types and two newly generated scRNA-seq datasets of rare cancer types, namely epithelial-myoepithelial carcinoma (EMC) and mucoepidermoid carcinoma (MEC), expanded our understanding of CAF heterogeneity. Cell-cell interaction analysis conducted within the spatial context highlighted the pivotal roles of matrix CAFs (mCAFs) in tumor angiogenesis and inflammatory CAFs (iCAFs) in shaping the immunosuppressive microenvironment. In patients with breast cancer (BRCA) undergoing anti-PD-1 immunotherapy, iCAFs demonstrated heightened capacity in facilitating cancer cell proliferation, promoting epithelial-mesenchymal transition (EMT), and contributing to the establishment of an immunosuppressive microenvironment. Furthermore, a scoring system based on iCAFs showed a significant correlation with immune therapy response in melanoma patients. Lastly, we provided a web interface (https://chenxisd.shinyapps.io/pancaf/) for the research community to investigate CAFs in the context of pan-cancer.}, }
@article {pmid37831574, year = {2023}, author = {Koh, H}, title = {Subgroup Identification Using Virtual Twins for Human Microbiome Studies.}, journal = {IEEE/ACM transactions on computational biology and bioinformatics}, volume = {20}, number = {6}, pages = {3800-3808}, doi = {10.1109/TCBB.2023.3324139}, pmid = {37831574}, issn = {1557-9964}, mesh = {Humans ; *Microbiota/genetics ; Precision Medicine ; Machine Learning ; }, abstract = {Even when the same treatment is employed, some patients are cured, while others are not. The patients that are cured may have beneficial microbes in their body that can boost treatment effects, but it is vice versa for the patients that are not cured. That is, treatment effects can vary depending on the patient's microbiome. If the effects of candidate treatments are well-predicted based on the patient's microbiome, we can select a treatment that is suited to the patient's microbiome or alter the patient's microbiome to improve treatment effects. Here, I introduce a streamlined analytic method, microbiome virtual twins (MiVT), to probe for the interplay between microbiome and treatment. MiVT employs a new prediction method, distance-based machine learning (dML), to improve prediction accuracy in microbiome studies and a new significance test, bootstrap-based test for regression tree (BoRT), to test if each subgroup's treatment effect is the same with the overall treatment effect. MiVT will serve as a useful guideline in microbiome-based personalized medicine to select the therapy that is most suited to the patient's microbiome or to tune the patient's microbiome to be suited to the treatment.}, }
@article {pmid37820693, year = {2023}, author = {Legakis, I and Chrousos, GP and Chatzipanagiotou, S}, title = {Thyroid Diseases and Intestinal Microbiome.}, journal = {Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme}, volume = {55}, number = {12}, pages = {813-818}, doi = {10.1055/a-2190-3847}, pmid = {37820693}, issn = {1439-4286}, mesh = {Humans ; *Gastrointestinal Microbiome ; *Thyroid Diseases ; *Hashimoto Disease ; *Autoimmune Diseases ; *Thyroid Neoplasms ; }, abstract = {The human microbiome plays an integral role in health. In particular, it is important for the development, differentiation, and maturation of the immune system, 70% of which resides in the intestinal mucosa. Microbiome studies conducted to date have revealed an association between disturbances in the microbiota (dysbiosis) and various pathological disorders, including changes in host immune status. Autoimmune thyroid diseases are one of the most common organ-specific autoimmune disorders, with a worldwide prevalence higher than 5%. The predominant autoimmune thyroid diseases are Hashimoto's thyroiditis and Grave's disease. Several factors, such as genetic and environmental ones, have been studied. In accordance with recent studies, it is assumed that the gut microbiome might play a significant role in triggering autoimmune diseases of the thyroid gland. However, the exact etiology has not yet been elucidated. The present review aims to describe the work carried out so far regarding the role of gut microflora in the pathogenesis of autoimmune thyroid diseases and its involvement in the appearance of benign nodules and papillary thyroid cancer. It appears that future work is needed to elucidate more precisely the mechanism for gut microbiota involvement in the development of autoimmune thyroid diseases.}, }
@article {pmid37819042, year = {2024}, author = {Zhou, T and Xiao, L and Zuo, Z and Zhao, F}, title = {MAMI: a comprehensive database of mother-infant microbiome and probiotic resources.}, journal = {Nucleic acids research}, volume = {52}, number = {D1}, pages = {D738-D746}, pmid = {37819042}, issn = {1362-4962}, support = {2022YFA1303900//National Key R&amp;D Program of China/ ; 32001082//National Natural Science Foundation of China/ ; }, mesh = {Female ; Humans ; Infant ; Infant, Newborn ; Pregnancy ; *Microbiota ; Probiotics ; Maternal-Fetal Exchange ; }, abstract = {Extensive evidence has demonstrated that the human microbiome and probiotics confer great impacts on human health, particularly during critical developmental stages such as pregnancy and infancy when microbial communities undergo remarkable changes and maturation. However, a major challenge in understanding the microbial community structure and interactions between mothers and infants lies in the current lack of comprehensive microbiome databases specifically focused on maternal and infant health. To address this gap, we have developed an extensive database called MAMI (Microbiome Atlas of Mothers and Infants) that archives data on the maternal and neonatal microbiome, as well as abundant resources on edible probiotic strains. By leveraging this resource, we can gain profound insights into the dynamics of microbial communities, contributing to lifelong wellness for both mothers and infants through precise modulation of the developing microbiota. The functionalities incorporated into MAMI provide a unique perspective on the study of the mother-infant microbiome, which not only advance microbiome-based scientific research but also enhance clinical practice. MAMI is publicly available at https://bioinfo.biols.ac.cn/mami/.}, }
@article {pmid37815708, year = {2024}, author = {Higashi, DL and Zou, Z and Qin, H and Kreth, J and Merritt, J}, title = {Employing Cloning-Independent Mutagenesis of Parvimonas micra for the Study of Cell Wall Biogenesis.}, journal = {Methods in molecular biology (Clifton, N.J.)}, volume = {2727}, number = {}, pages = {57-67}, pmid = {37815708}, issn = {1940-6029}, support = {R01 DE029492/DE/NIDCR NIH HHS/United States ; R21 DE029612/DE/NIDCR NIH HHS/United States ; R35 DE028252/DE/NIDCR NIH HHS/United States ; }, mesh = {Humans ; *Firmicutes/genetics ; *Microbiota ; Mutagenesis ; Cloning, Molecular ; }, abstract = {The cell wall plays an important structural role for bacteria and is intimately tied to a variety of critical processes ranging from growth and differentiation to pathogenesis. Our understanding of cell wall biogenesis is primarily derived from a relatively small number of heavily studied model organisms. Consequently, these processes can only be inferred for the vast majority of prokaryotes, especially among groups of uncharacterized and/or genetically intractable organisms. Recently, we developed the first tractable genetic system for Parvimonas micra, which is a ubiquitous Gram-positive pathobiont of the human microbiome involved in numerous types of inflammatory infections as well as a variety of malignant tumors. P. micra is also the first, and currently only, member of the entire Tissierellia class of the Bacillota phylum in which targeted genetic manipulation has been demonstrated. Thus, it is now possible to study cell wall biogenesis mechanisms within a member of the Tissierellia, which may also reveal novel aspects of P. micra pathobiology. Herein, we describe a procedure for cloning-independent genetic manipulation of P. micra, including allelic replacement mutagenesis and genetic complementation. The described techniques are also similarly applicable for the study of other aspects of P. micra pathobiology and physiology.}, }
@article {pmid37811798, year = {2023}, author = {Lohse, MB and Ziv, N and Johnson, AD}, title = {Variation in transcription regulator expression underlies differences in white-opaque switching between the SC5314 reference strain and the majority of Candida albicans clinical isolates.}, journal = {Genetics}, volume = {225}, number = {3}, pages = {}, pmid = {37811798}, issn = {1943-2631}, support = {P30 CA082103/CA/NCI NIH HHS/United States ; R01 AI049187/AI/NIAID NIH HHS/United States ; R01 AI175080/AI/NIAID NIH HHS/United States ; R01 GM037049/GM/NIGMS NIH HHS/United States ; }, mesh = {Humans ; *Candida albicans/metabolism ; *Fungal Proteins/genetics/metabolism ; Genes, Mating Type, Fungal ; Phenotype ; Cell Communication ; Gene Expression Regulation, Fungal ; }, abstract = {Candida albicans, a normal member of the human microbiome and an opportunistic fungal pathogen, undergoes several morphological transitions. One of these transitions is white-opaque switching, where C. albicans alternates between 2 stable cell types with distinct cellular and colony morphologies, metabolic preferences, mating abilities, and interactions with the innate immune system. White-to-opaque switching is regulated by mating type; it is repressed by the a1/α2 heterodimer in a/α cells, but this repression is lifted in a/a and α/α mating type cells (each of which are missing half of the repressor). The widely used C. albicans reference strain, SC5314, is unusual in that white-opaque switching is completely blocked when the cells are a/α; in contrast, most other C. albicans a/α strains can undergo white-opaque switching at an observable level. In this paper, we uncover the reason for this difference. We show that, in addition to repression by the a1/α2 heterodimer, SC5314 contains a second block to white-opaque switching: 4 transcription regulators of filamentous growth are upregulated in this strain and collectively suppress white-opaque switching. This second block is missing in the majority of clinical strains, and, although they still contain the a1/α2 heterodimer repressor, they exhibit a/α white-opaque switching at an observable level. When both blocks are absent, white-opaque switching occurs at very high levels. This work shows that white-opaque switching remains intact across a broad group of clinical strains, but the precise way it is regulated and therefore the frequency at which it occurs varies from strain to strain.}, }
@article {pmid37808321, year = {2023}, author = {D'Elia, D and Truu, J and Lahti, L and Berland, M and Papoutsoglou, G and Ceci, M and Zomer, A and Lopes, MB and Ibrahimi, E and Gruca, A and Nechyporenko, A and Frohme, M and Klammsteiner, T and Pau, ECS and Marcos-Zambrano, LJ and Hron, K and Pio, G and Simeon, A and Suharoschi, R and Moreno-Indias, I and Temko, A and Nedyalkova, M and Apostol, ES and Truică, CO and Shigdel, R and Telalović, JH and Bongcam-Rudloff, E and Przymus, P and Jordamović, NB and Falquet, L and Tarazona, S and Sampri, A and Isola, G and Pérez-Serrano, D and Trajkovik, V and Klucar, L and Loncar-Turukalo, T and Havulinna, AS and Jansen, C and Bertelsen, RJ and Claesson, MJ}, title = {Advancing microbiome research with machine learning: key findings from the ML4Microbiome COST action.}, journal = {Frontiers in microbiology}, volume = {14}, number = {}, pages = {1257002}, pmid = {37808321}, issn = {1664-302X}, abstract = {The rapid development of machine learning (ML) techniques has opened up the data-dense field of microbiome research for novel therapeutic, diagnostic, and prognostic applications targeting a wide range of disorders, which could substantially improve healthcare practices in the era of precision medicine. However, several challenges must be addressed to exploit the benefits of ML in this field fully. In particular, there is a need to establish "gold standard" protocols for conducting ML analysis experiments and improve interactions between microbiome researchers and ML experts. The Machine Learning Techniques in Human Microbiome Studies (ML4Microbiome) COST Action CA18131 is a European network established in 2019 to promote collaboration between discovery-oriented microbiome researchers and data-driven ML experts to optimize and standardize ML approaches for microbiome analysis. This perspective paper presents the key achievements of ML4Microbiome, which include identifying predictive and discriminatory 'omics' features, improving repeatability and comparability, developing automation procedures, and defining priority areas for the novel development of ML methods targeting the microbiome. The insights gained from ML4Microbiome will help to maximize the potential of ML in microbiome research and pave the way for new and improved healthcare practices.}, }
@article {pmid37806533, year = {2024}, author = {McGuinness, AJ and Stinson, LF and Snelson, M and Loughman, A and Stringer, A and Hannan, AJ and Cowan, CSM and Jama, HA and Caparros-Martin, JA and West, ML and Wardill, HR and , }, title = {From hype to hope: Considerations in conducting robust microbiome science.}, journal = {Brain, behavior, and immunity}, volume = {115}, number = {}, pages = {120-130}, doi = {10.1016/j.bbi.2023.09.022}, pmid = {37806533}, issn = {1090-2139}, mesh = {Humans ; Reproducibility of Results ; *Microbiota ; Machine Learning ; }, abstract = {Microbiome science has been one of the most exciting and rapidly evolving research fields in the past two decades. Breakthroughs in technologies including DNA sequencing have meant that the trillions of microbes (particularly bacteria) inhabiting human biological niches (particularly the gut) can be profiled and analysed in exquisite detail. This microbiome profiling has profound impacts across many fields of research, especially biomedical science, with implications for how we understand and ultimately treat a wide range of human disorders. However, like many great scientific frontiers in human history, the pioneering nature of microbiome research comes with a multitude of challenges and potential pitfalls. These include the reproducibility and robustness of microbiome science, especially in its applications to human health outcomes. In this article, we address the enormous promise of microbiome science and its many challenges, proposing constructive solutions to enhance the reproducibility and robustness of research in this nascent field. The optimisation of microbiome science spans research design, implementation and analysis, and we discuss specific aspects such as the importance of ecological principals and functionality, challenges with microbiome-modulating therapies and the consideration of confounding, alternative options for microbiome sequencing, and the potential of machine learning and computational science to advance the field. The power of microbiome science promises to revolutionise our understanding of many diseases and provide new approaches to prevention, early diagnosis, and treatment.}, }
@article {pmid37800929, year = {2023}, author = {Hisatomi, A and Tourlousse, DM and Hamajima, M and Ohkuma, M and Sekiguchi, Y and Sakamoto, M}, title = {Complete genome sequences of Ruminococcus torques strains JCM 36208 and JCM 36209, isolated from the feces of a healthy Japanese male.}, journal = {Microbiology resource announcements}, volume = {12}, number = {11}, pages = {e0063223}, pmid = {37800929}, issn = {2576-098X}, support = {JP22ae0121035//Japan Agency for Medical Research and Development (AMED)/ ; }, abstract = {Here, we report the complete genome sequences of two Ruminococcus torques strains (JCM 36208 and JCM 36209) that were newly isolated from the feces of a healthy Japanese male. Both genomes consist of a single circular chromosome with a length of ~2.8 Mbp and a G+C content of 41.8%.}, }
@article {pmid37797477, year = {2023}, author = {Ückert, AK and Rütschlin, S and Gutbier, S and Wörz, NC and Miah, MR and Martins, AC and Hauer, I and Holzer, AK and Meyburg, B and Mix, AK and Hauck, C and Aschner, M and Böttcher, T and Leist, M}, title = {Identification of the bacterial metabolite aerugine as potential trigger of human dopaminergic neurodegeneration.}, journal = {Environment international}, volume = {180}, number = {}, pages = {108229}, pmid = {37797477}, issn = {1873-6750}, support = {R01 ES007331/ES/NIEHS NIH HHS/United States ; R01 ES010563/ES/NIEHS NIH HHS/United States ; }, mesh = {Animals ; Humans ; *Caenorhabditis elegans/metabolism ; Animals, Genetically Modified ; *Parkinson Disease ; Antioxidants/metabolism ; Neurons ; }, abstract = {The causes of nigrostriatal cell death in idiopathic Parkinson's disease are unknown, but exposure to toxic chemicals may play some role. We followed up here on suggestions that bacterial secondary metabolites might be selectively cytotoxic to dopaminergic neurons. Extracts from Streptomyces venezuelae were found to kill human dopaminergic neurons (LUHMES cells). Utilizing this model system as a bioassay, we identified a bacterial metabolite known as aerugine (C10H11NO2S; 2-[4-(hydroxymethyl)-4,5-dihydro-1,3-thiazol-2-yl]phenol) and confirmed this finding by chemical re-synthesis. This 2-hydroxyphenyl-thiazoline compound was previously shown to be a product of a wide-spread biosynthetic cluster also found in the human microbiome and in several pathogens. Aerugine triggered half-maximal dopaminergic neurotoxicity at 3-4 µM. It was less toxic for other neurons (10-20 µM), and non-toxic (at <100 µM) for common human cell lines. Neurotoxicity was completely prevented by several iron chelators, by distinct anti-oxidants and by a caspase inhibitor. In the Caenorhabditis elegans model organism, general survival was not affected by aerugine concentrations up to 100 µM. When transgenic worms, expressing green fluorescent protein only in their dopamine neurons, were exposed to aerugine, specific neurodegeneration was observed. The toxicant also exerted functional dopaminergic toxicity in nematodes as determined by the "basal slowing response" assay. Thus, our research has unveiled a bacterial metabolite with a remarkably selective toxicity toward human dopaminergic neurons in vitro and for the dopaminergic nervous system of Caenorhabditis elegans in vivo. These findings suggest that microbe-derived environmental chemicals should be further investigated for their role in the pathogenesis of Parkinson's disease.}, }
@article {pmid37792894, year = {2023}, author = {Pompei, S and Bella, E and Weitz, JS and Grilli, J and Lagomarsino, MC}, title = {Metacommunity structure preserves genome diversity in the presence of gene-specific selective sweeps under moderate rates of horizontal gene transfer.}, journal = {PLoS computational biology}, volume = {19}, number = {10}, pages = {e1011532}, pmid = {37792894}, issn = {1553-7358}, mesh = {Humans ; *Gene Transfer, Horizontal/genetics ; *Bacteria/genetics ; Biological Evolution ; Genome ; }, abstract = {The horizontal transfer of genes is fundamental for the eco-evolutionary dynamics of microbial communities, such as oceanic plankton, soil, and the human microbiome. In the case of an acquired beneficial gene, classic population genetics would predict a genome-wide selective sweep, whereby the genome spreads clonally within the community and together with the beneficial gene, removing genome diversity. Instead, several sources of metagenomic data show the existence of "gene-specific sweeps", whereby a beneficial gene spreads across a bacterial community, maintaining genome diversity. Several hypotheses have been proposed to explain this process, including the decreasing gene flow between ecologically distant populations, frequency-dependent selection from linked deleterious allelles, and very high rates of horizontal gene transfer. Here, we propose an additional possible scenario grounded in eco-evolutionary principles. Specifically, we show by a mathematical model and simulations that a metacommunity where species can occupy multiple patches, acting together with a realistic (moderate) HGT rate, helps maintain genome diversity. Assuming a scenario of patches dominated by single species, our model predicts that diversity only decreases moderately upon the arrival of a new beneficial gene, and that losses in diversity can be quickly restored. We explore the generic behaviour of diversity as a function of three key parameters, frequency of insertion of new beneficial genes, migration rates and horizontal transfer rates.Our results provides a testable explanation for how diversity can be maintained by gene-specific sweeps even in the absence of high horizontal gene transfer rates.}, }
@article {pmid37791672, year = {2023}, author = {Shittu, AR and Iwaloye, OF and Ojewole, AE and Rabiu, AG and Amechi, MO and Herve, OF}, title = {The effects of per- and polyfluoroalkyl substances on environmental and human microorganisms and their potential for bioremediation.}, journal = {Arhiv za higijenu rada i toksikologiju}, volume = {74}, number = {3}, pages = {167-178}, pmid = {37791672}, issn = {1848-6312}, mesh = {Humans ; Biodegradation, Environmental ; *Drug Contamination ; Escherichia coli ; Soil ; *Fluorocarbons/toxicity ; }, abstract = {Utilised in a variety of consumer products, per- and polyfluoroalkyl substances (PFAS) are major environmental contaminants that accumulate in living organisms due to their highly hydrophobic, lipophobic, heat-resistant, and non-biodegradable properties. This review summarizes their effects on microbial populations in soils, aquatic and biogeochemical systems, and the human microbiome. Specific microbes are insensitive to and even thrive with PFAS contamination, such as Escherichia coli and the Proteobacteria in soil and aquatic environments, while some bacterial species, such as Actinobacteria and Chloroflexi, are sensitive and drop in population. Some bacterial species, in turn, have shown success in PFAS bioremediation, such as Acidimicrobium sp. and Pseudomonas parafulva.}, }
@article {pmid37790536, year = {2023}, author = {Wakade, RS and Krysan, DJ}, title = {Comparative dynamics of gene expression during in vitro and in vivo Candida albicans filamentation.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {37790536}, issn = {2692-8205}, support = {R01 AI133409/AI/NIAID NIH HHS/United States ; }, abstract = {Candida albicans is one of them most common causes of fungal disease in humans and is a commensal member of the human microbiome. The ability of C. albicans to cause disease is tightly correlated with its ability to undergo a morphological transition from budding yeast to a filamentous form (hyphae and pseudohyphae). This morphological transition is accompanied by the induction of a set of well characterized hyphae-associated genes and transcriptional regulators. To date, the vast majority of data regarding this process has been based on in vitro studies of filamentation using a range of inducing conditions. Recently, we developed an in vivo imaging approach that allows the direct characterization of morphological transition during mammalian infection. Here, we couple this imaging assay with in vivo expression profiling to characterize the time course of in vivo filamentation and the accompanying changes in gene expression. We also compare in vivo observations to in vitro filamentation using a medium (RPMI 1640 tissue culture medium with 10% bovine calf serum) widely used to mimic host conditions. From these data, we make the following conclusions regarding in vivo and in vitro filamentation. First, the transcriptional programs regulating filamentation are rapidly induced in vitro and in vivo. Second, the tempo of filamentation in vivo is prolonged relative to in vitro filamentation and the period of high expression of genes associated with that process is also prolonged. Third, hyphae are adapting to changing infection environments after filamentation has reached steady-state.}, }
@article {pmid37786407, year = {2023}, author = {Pietilä, JP and Häkkinen, TA and Pakarinen, L and Ollgren, J and Kantele, A}, title = {Treatment of Dientamoeba fragilis: A retrospective Finnish analysis of faecal clearance and clinical cure comparing four antiprotozoal drugs.}, journal = {New microbes and new infections}, volume = {54}, number = {}, pages = {101179}, pmid = {37786407}, issn = {2052-2975}, abstract = {BACKGROUND: Dientamoeba fragilis (DF), the most common intestinal protozoal pathogen in affluent countries, causes asymptomatic or symptomatic infections with severity ranging from mild to disabling. Currently, many studies of treatment options only have small sample sizes and report results that are partly contradictory.<br><br>METHODS: Investigating data retrieved from Helsinki University Hospital and Helsinki City patient records, we searched for the most effective antiprotozoal in treating DF infections. To study microbiological clearance of DF, we collected laboratory results of control samples from patients given one of four commonly used antiprotozoals: doxycycline, metronidazole, paromomycin, or secnidazole. For patients symptomatic prior to antiprotozoal treatment, we also retrieved data on clinical outcomes. Furthermore, we explored factors associated with faecal clearance and clinical cure.<br><br>RESULTS: A total of 369 patients (median age 38) and 492 treatment episodes were included. Paromomycin (n&#xa0;&#x200b;=&#xa0;&#x200b;297) proved effective (clearance rate 83%), showing strong association with faecal clearance (aOR 18.08 [7.24-45.16], p&#xa0;&#x200b;<&#xa0;&#x200b;0.001). For metronidazole the rate was 42% (n&#xa0;&#x200b;=&#xa0;&#x200b;84), for secnidazole 37% (n&#xa0;&#x200b;=&#xa0;&#x200b;79), and doxycycline 22% (n&#xa0;&#x200b;=&#xa0;&#x200b;32). In pairwise comparisons, paromomycin outdid the three other regimens (p&#xa0;&#x200b;<&#xa0;&#x200b;0.001, &#x3c7;[2] test). Faecal clearance was associated with clinical cure (aOR 5.85 [3.02-11.32], p&#xa0;&#x200b;<&#xa0;&#x200b;0.001).<br><br>CONCLUSIONS: Faecal clearance, strongly associated with clinical cure, is most effectively achieved with a course of paromomycin, followed by metronidazole, secnidazole and doxycycline. Our findings will be useful in devising treatment guidelines for adults with symptomatic D.&#xa0;fragilis infection.}, }
@article {pmid37781374, year = {2023}, author = {Zhang, J and Deng, J and Li, J and Su, Y and Hu, J and Lin, D and Su, M and Chen, Y and Liao, S and Bai, X and Lv, M and Xu, T and Zhong, Q and Guo, X}, title = {Changes of gut microbiota under different nutritional methods in elderly patients with severe COVID-19 and their relationship with prognosis.}, journal = {Frontiers in immunology}, volume = {14}, number = {}, pages = {1260112}, pmid = {37781374}, issn = {1664-3224}, mesh = {Humans ; Aged ; *Gastrointestinal Microbiome ; *COVID-19/therapy ; SARS-CoV-2 ; Prognosis ; Parenteral Nutrition/methods ; }, abstract = {BACKGROUND: The clinical progression of individuals afflicted with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection exhibits significant heterogeneity, particularly affecting the elderly population to a greater extent. Consequently, the association between nutrition and microbiota has garnered considerable interest. Hence, the objective of this study was to gather clinical data pertaining to the influence of diverse nutritional support interventions on the prognosis of geriatric patients with COVID-19, while additionally examining the fecal microbiota of these individuals to assess the repercussions of microecological alterations on their prognostic outcomes.<br><br>RESULTS: A total of 71 elderly patients diagnosed with severe COVID-19 were included in this study. These patients were subsequently divided into two groups, namely the enteral nutrition (EN) group and the parenteral nutrition (PN) group, based on the type of nutritional support therapy they received after admission. The occurrence of complications was observed in 10.4% of patients in the EN group, whereas it was significantly higher at 69.6% in the PN group (P<0.001). Furthermore, the 60-day mortality rate was 2.1% (1/48) in the EN group, while it was notably higher at 30.4% (7/23) in the PN group (P=0.001). To identify the independent predictors of 60-day mortality, stepwise logistic regression analysis was employed. Among different bacterial groups, Enterococcus_faecium (18.19%) and Pseudomonas_aeruginosa (1.91%) had higher average relative abundance in the PN group (P<0.05). However, the relative abundance of Ruminococcus was higher in the EN group. Further Spearman correlation analysis showed that Enterococcus_faecium was positively correlated with poor clinical prognosis, while Ruminococcus was negatively correlated with poor clinical prognosis.<br><br>CONCLUSIONS: This study shows that the changes in the composition of intestinal flora in elderly COVID-19 patients receiving different nutritional support strategies may be related to different clinical outcomes. The abundance of Enterococcus_faecium in elderly COVID-19 patients receiving PN is significantly increased and is closely related to poor clinical outcomes. It highlights the potential of microbiome-centric interventions to mitigate and manage COVID-19 in older adults with different nutritional support options.}, }
@article {pmid37776987, year = {2023}, author = {Liu, S and Zhang, S and Guo, M and Lei, Q and He, L and Li, Z}, title = {Acoustic stimulation during sleep improves cognition and ameliorates Alzheimer's disease pathology in APP/PS1 mice.}, journal = {Experimental gerontology}, volume = {182}, number = {}, pages = {112299}, doi = {10.1016/j.exger.2023.112299}, pmid = {37776987}, issn = {1873-6815}, abstract = {Nonpharmacological therapies for Alzheimer's disease (AD) have become a popular research topic, and acoustic stimulation during sleep is one such promising strategy for the clinical treatment of AD. Some animal experiments have illustrated that acoustic stimulation at a specific frequency can ameliorate AD-related pathology or improve cognition in mice, but these studies did not explore the effective time window of auditory stimulation. Here, we explored the effects of acoustic stimulation during wakefulness and acoustic stimulation during sleep on cognition and AD-related pathology in APP/PS1 mice and the underlying mechanisms. In this study, forty APP/PS1 mice were equally divided into the following 4 groups and treated for 28 days: the chronic sleep deprivation (CSD) group (exposed to sleep deprivation from zeitgeber time [ZT] 0 to ZT 12 each day), the normal sleep and stress exposure (NSS) group (exposed to a stressor from ZT 0 to ZT 12 each day), the acoustic stimulation during wakefulness (ASW) group (exposed to sleep deprivation and 40 Hz acoustic stimulation from ZT 0 to ZT 12 each day) and the acoustic stimulation during sleep (ASS) group (exposed to sleep deprivation from ZT 0 to ZT 12 and 40 Hz acoustic stimulation from ZT 12 to ZT 24 each day). After the intervention, cognition was assessed by behavioural experiments. The amyloid-β burden was analysed by Western blotting, immunofluorescence and enzyme-linked immunosorbent assay. Tau pathology was assessed by Western blotting. Mitochondrial function was evaluated by transmission electron microscopy, Western blotting and fluorescence intensity measurement. We found that the NSS and ASS groups had better cognitive functions than the CSD and ASW groups. The Aβ burden and tau phosphorylation were lower in the NSS and ASS groups than in the CSD and ASW groups. Mitochondrial function was better in the NSS and ASS groups than in the CSD and ASW groups. However, the differences in these parameters between the NSS and ASS groups and between the CSD and ASW groups were not significant. Our findings suggest that acoustic stimulation at a specific frequency during sleep, but not during wakefulness, reduces the amyloid-β burden by inhibiting amyloid beta precursor protein-binding protein 2, hinders tau phosphorylation by blocking glycogen synthase kinase 3 beta, and restores mitochondrial function by elevating mitophagy and promoting mitochondrial biogenesis.}, }
@article {pmid37770743, year = {2023}, author = {Bader, AC and Van Zuylen, EM and Handsley-Davis, M and Alegado, RA and Benezra, A and Pollet, RM and Ehau-Taumaunu, H and Weyrich, LS and Anderson, MZ}, title = {A relational framework for microbiome research with Indigenous communities.}, journal = {Nature microbiology}, volume = {8}, number = {10}, pages = {1768-1776}, pmid = {37770743}, issn = {2058-5276}, mesh = {Humans ; *Population Groups ; *Microbiota ; }, abstract = {Ethical practices in human microbiome research have failed to keep pace with scientific advances in the field. Researchers seeking to 'preserve' microbial species associated with Indigenous groups, but absent from industrialized populations, have largely failed to include Indigenous people in knowledge co-production or benefit, perpetuating a legacy of intellectual and material extraction. We propose a framework centred on relationality among Indigenous peoples, researchers and microbes, to guide ethical microbiome research. Our framework centres accountability to flatten historical power imbalances that favour researcher perspectives and interests to provide space for Indigenous worldviews in pursuit of Indigenous research sovereignty. Ethical inclusion of Indigenous communities in microbiome research can provide health benefits for all populations and reinforce mutually beneficial partnerships between researchers and the public.}, }
@article {pmid37764046, year = {2023}, author = {Efremova, I and Maslennikov, R and Poluektova, E and Zharkova, M and Kudryavtseva, A and Krasnov, G and Fedorova, M and Shirokova, E and Kozlov, E and Levshina, A and Ivashkin, V}, title = {Gut Dysbiosis and Hemodynamic Changes as Links of the Pathogenesis of Complications of Cirrhosis.}, journal = {Microorganisms}, volume = {11}, number = {9}, pages = {}, pmid = {37764046}, issn = {2076-2607}, support = {National Research Grant Russia 2019//Biocodex (France)/ ; }, abstract = {The aim was to evaluate the relationship between gut dysbiosis and hemodynamic changes (hyperdynamic circulation) in cirrhosis, and between hemodynamic changes and complications of this disease. This study included 47 patients with cirrhosis. Stool microbiome was assessed using 16S rRNA gene sequencing. Echocardiography with a simultaneous assessment of blood pressure and heart rate was performed to assess systemic hemodynamics. Patients with hyperdynamic circulation had more severe cirrhosis, lower albumin, sodium and prothrombin levels, higher C-reactive protein, aspartate aminotransferase and total bilirubin levels, and higher incidences of portopulmonary hypertension, ascites, overt hepatic encephalopathy, hypoalbuminemia, hypoprothrombinemia, systemic inflammation, and severe hyperbilirubinemia than patients with normodynamic circulation. Patients with hyperdynamic circulation compared with those with normodynamic circulation had increased abundance of Proteobacteria, Enterobacteriaceae, Bacilli, Streptococcaceae, Lactobacillaceae, Fusobacteria, Micrococcaceae, Intestinobacter, Clostridium sensu stricto, Proteus and Rumicoccus, and decreased abundance of Bacteroidetes, Bacteroidaceae, Holdemanella, and Butyrivibrio. The systemic vascular resistance and cardiac output values correlated with the abundance of Proteobacteria, Enterobacteriaceae, Bacilli, Streptococcaceae, Lactobacillaceae, Micrococcaceae, and Fusobacteria. Heart rate and cardiac output value were negatively correlated with the abundance of Bacteroidetes. The mean pulmonary artery pressure value was positively correlated with the abundance of Proteobacteria and Micrococcaceae, and negatively with the abundance of Holdemanella.}, }
@article {pmid37763004, year = {2023}, author = {Kovaleva, A and Poluektova, E and Maslennikov, R and Karchevskaya, A and Shifrin, O and Kiryukhin, A and Tertychnyy, A and Kovalev, L and Kovaleva, M and Lobanova, O and Kudryavtseva, A and Krasnov, G and Fedorova, M and Ivashkin, V}, title = {Effect of Rebamipide on the Intestinal Barrier, Gut Microbiota Structure and Function, and Symptom Severity Associated with Irritable Bowel Syndrome and Functional Dyspepsia Overlap: A Randomized Controlled Trial.}, journal = {Journal of clinical medicine}, volume = {12}, number = {18}, pages = {}, pmid = {37763004}, issn = {2077-0383}, abstract = {Treatment of functional digestive disorders is not always effective. Therefore, a search for new application points for potential drugs is perspective. Our aim is to evaluate the effect of rebamipide on symptom severity, intestinal barrier status, and intestinal microbiota composition and function in patients with diarrheal variant of irritable bowel syndrome overlapping with functional dyspepsia (D-IBSoFD). Sixty patients were randomized to receive trimebutine (TRI group), trimebutine + rebamipide (T + R group), or rebamipide (REB group) for 2 months. At the beginning and end of the study, patients were assessed for general health (SF-36), severity of digestive symptoms (Gastrointestinal Symptom Rating and 7 × 7 scales), state of the intestinal barrier, and composition (16S rRNA gene sequencing) and function (short-chain fatty acid fecal content) of the gut microbiota. The severity of most digestive symptoms was reduced in the REB and T + R groups to levels similar to that observed in the TRI group. The duodenal and sigmoidal lymphocytic and sigmoidal eosinophilic infiltration was decreased only in the REB and T + R groups, not in the TRI group. Serum zonulin levels were significantly decreased only in the REB group. A decrease in intraepithelial lymphocytic infiltration in the duodenum correlated with a decrease in the severity of rumbling and flatulence, while a decrease in infiltration within the sigmoid colon correlated with improved stool consistency and decreased severity of the sensation of incomplete bowel emptying. In conclusion, rebamipide improves the intestinal barrier condition and symptoms in D-IBSoFD. The rebamipide effects are not inferior to those of trimebutine.}, }
@article {pmid37762089, year = {2023}, author = {Mousa, WK and Mousa, S and Ghemrawi, R and Obaid, D and Sarfraz, M and Chehadeh, F and Husband, S}, title = {Probiotics Modulate Host Immune Response and Interact with the Gut Microbiota: Shaping Their Composition and Mediating Antibiotic Resistance.}, journal = {International journal of molecular sciences}, volume = {24}, number = {18}, pages = {}, pmid = {37762089}, issn = {1422-0067}, support = {Ph2022-3-100//Al Ain University of Science and Technology/ ; }, mesh = {Humans ; *Gastrointestinal Microbiome ; Caco-2 Cells ; Drug Resistance, Microbial ; Anti-Bacterial Agents/pharmacology ; Immunity ; }, abstract = {The consortium of microbes inhabiting the human body, together with their encoded genes and secreted metabolites, is referred to as the "human microbiome." Several studies have established a link between the composition of the microbiome and its impact on human health. This impact spans local gastrointestinal inflammation to systemic autoimmune disorders and neurodegenerative diseases such as Alzheimer's and Autism. Some of these links have been validated by rigorous experiments that identify specific strains as mediators or drivers of a particular condition. Consequently, the development of probiotics to compensate for a missing beneficial microbe(s) has advanced and become popular, especially in the treatment of irritable bowel diseases and to restore disrupted gut flora after antibiotic administration. The widespread use of probiotics is often advocated as a natural ecological therapy. However, this perception is not always accurate, as there is a potential for unexpected interactions when administering live microbial cultures. Here, we designed this research to explore the intricate interactions among probiotics, the host, and microbes through a series of experiments. Our objectives included assessing their immunomodulatory effects, response to oral medications, impact on microbial population dynamics, and mediation of antibiotic resistance. To achieve these goals, we employed diverse experimental protocols, including cell-based enzyme -linked immunosorbent assay (ELISA), antibiotic susceptibility testing, antimicrobial activity assays, computational prediction of probiotic genes responsible for antibiotic resistance, polymerase chain reaction (PCR)-based validation of predicted genes, and survival assays of probiotics in the presence of selected oral medications. Our findings highlight that more than half of the tested probiotics trigger an inflammatory response in the Caco-2 cell line, are influenced by oral medications, exhibit antibacterial activity, and possess genes encoding antimicrobial resistance. These results underscore the necessity for a reevaluation of probiotic usage and emphasize the importance of establishing regulations to govern probiotic testing, approval, and administration.}, }
@article {pmid37757827, year = {2023}, author = {Blaustein, RA and Shen, Z and Kashaf, SS and Lee-Lin, S and Conlan, S and ,  and Bosticardo, M and Delmonte, OM and Holmes, CJ and Taylor, ME and Banania, G and Nagao, K and Dimitrova, D and Kanakry, JA and Su, H and Holland, SM and Bergerson, JRE and Freeman, AF and Notarangelo, LD and Kong, HH and Segre, JA}, title = {Expanded microbiome niches of RAG-deficient patients.}, journal = {Cell reports. Medicine}, volume = {4}, number = {10}, pages = {101205}, pmid = {37757827}, issn = {2666-3791}, support = {T32 HD007009/HD/NICHD NIH HHS/United States ; }, mesh = {Humans ; *Microbiota/genetics ; *Gastrointestinal Microbiome/genetics ; Skin ; Metagenome ; }, abstract = {The complex interplay between microbiota and immunity is important to human health. To explore how altered adaptive immunity influences the microbiome, we characterize skin, nares, and gut microbiota of patients with recombination-activating gene (RAG) deficiency-a rare genetically defined inborn error of immunity (IEI) that results in a broad spectrum of clinical phenotypes. Integrating de novo assembly of metagenomes from RAG-deficient patients with reference genome catalogs provides an expansive multi-kingdom view of microbial diversity. RAG-deficient patient microbiomes exhibit inter-individual variation, including expansion of opportunistic pathogens (e.g., Corynebacterium bovis, Haemophilus influenzae), and a relative loss of body site specificity. We identify 35 and 27 bacterial species derived from skin/nares and gut microbiomes, respectively, which are distinct to RAG-deficient patients compared to healthy individuals. Underscoring IEI patients as potential reservoirs for viral persistence and evolution, we further characterize the colonization of eukaryotic RNA viruses (e.g., Coronavirus 229E, Norovirus GII) in this patient population.}, }
@article {pmid37754546, year = {2023}, author = {Walker, JN and Hanson, BM and Hunter, T and Simar, SR and Duran Ramirez, JM and Obernuefemann, CLP and Parikh, RP and Tenenbaum, MM and Margenthaler, JA and Hultgren, SJ and Myckatyn, TM}, title = {A prospective randomized clinical trial to assess antibiotic pocket irrigation on tissue expander breast reconstruction.}, journal = {Microbiology spectrum}, volume = {11}, number = {5}, pages = {e0143023}, pmid = {37754546}, issn = {2165-0497}, support = {R01 DK051406/DK/NIDDK NIH HHS/United States ; }, abstract = {Bacterial infection is the most common complication following staged post-mastectomy breast reconstruction initiated with a tissue expander (TE). To limit bacterial infection, antibiotic irrigation of the surgical site is commonly performed despite little high-quality data to support this practice. We performed a prospective randomized control trial to compare the impact of saline irrigation alone to a triple antibiotic irrigation regimen (1 g cefazolin, 80 mg gentamicin, and 50,000 units of bacitracin in 500 mL of saline) for breast implant surgery. The microbiome in breasts with cancer (n = 16) was compared to those without (n = 16), as all patients (n = 16) had unilateral cancers but bilateral mastectomies (n = 32). Biologic and prosthetic specimens procured both at the time of mastectomy and during TE removal months later were analyzed for longitudinal comparison. Outcomes included clinical infection, bacterial abundance, and relative microbiome composition. No patient in either group suffered a reconstructive failure or developed an infection. Triple antibiotic irrigation administered at the time of immediate TE reconstruction did not reduce bacterial abundance or impact microbial diversity relative to saline irrigation at the time of planned exchange. Implanted prosthetic material adopted the microbial composition of the surrounding host tissue. In cancer-naïve breasts, relative to saline, antibiotic irrigation increased bacterial abundance on periprosthetic capsules (P = 0.03) and acellular dermal matrices (P = 0.04) and altered the microbiota on both. These data show that, relative to saline only, the use of triple antibiotic irrigation in TE breast reconstruction does impact the bacterial abundance and diversity of certain biomaterials from cancer-naïve breasts. IMPORTANCE The lifetime risk of breast cancer is ~13% in women and is treated with a mastectomy in ~50% of cases. The majority are reconstructed, usually starting with a tissue expander to help restore the volume for a subsequent permanent breast implant or the women's own tissues. The biopsychosocial benefits of breast reconstruction, though, can be tempered by a high complication rate of at least 7% but over 30% in some women. Bacterial infection is the most common complication, and can lead to treatment delays, patient physical and emotional distress and escalating health care cost. To limit this risk, plastic surgeons have tried a variety of strategies to limit bacterial infection including irrigating the pocket created after removing the breast implant with antibiotic solutions, but good-quality data are scarce. Herein, we study the value of antibiotics in pocket irrigation using a robust randomized clinical trial design and molecular microbiology approaches.}, }
@article {pmid37753524, year = {2023}, author = {Ejtahed, HS and Parsa, M and Larijani, B}, title = {Ethical challenges in conducting and the clinical application of human microbiome research.}, journal = {Journal of medical ethics and history of medicine}, volume = {16}, number = {}, pages = {5}, pmid = {37753524}, issn = {2008-0387}, }
@article {pmid37751622, year = {2023}, author = {Hyvönen, S and Tapiainen, T and Pokka, T and Solasaari, T and Korpela, K and de Vos, WM and Salonen, A and Kolho, KL}, title = {Perinatal and Other Risk Factors for Common Infections in Infancy: A Prospective Cohort Study.}, journal = {The Pediatric infectious disease journal}, volume = {42}, number = {12}, pages = {e447-e453}, pmid = {37751622}, issn = {1532-0987}, mesh = {Child ; Infant ; Pregnancy ; Male ; Humans ; Female ; *Cesarean Section/adverse effects ; Cohort Studies ; Prospective Studies ; Risk Factors ; Anti-Bacterial Agents/therapeutic use ; *Urinary Tract Infections/epidemiology/etiology ; }, abstract = {OBJECTIVE: Limited data from prospective cohort studies in high-income countries are available on the perinatal risk factors for common infections in children. Our hypothesis was that perinatal factors may be risk factors for infectious episodes during the first year of life.<br><br>METHODS: In this prospective Health and Early Life Microbiota birth cohort study of full-term infants (n = 1052) born in 2016-2018, the number and duration of infection episodes were collected online at weekly to monthly intervals. In a multivariate regression model, the main exposures were perinatal factors such as mode of delivery and intrapartum antibiotics. Environmental factors were additional exposures. The outcomes were the number and duration of infectious episodes in the first year of life.<br><br>RESULTS: The mean number of infection episodes was 4.2 (2.9 SD). The mean duration of infection symptoms was 44 days (40 SD). Upper respiratory infections accounted for 83% of the episodes (3674/4455). Perinatal factors were not associated with the number nor the duration of infection episodes, but cesarean section was associated with an increased occurrence of urinary tract infections in infancy [adjusted odds ratio (aOR): 3.6; 95% confidence interval (CI): 1.13-11.1]. Of the additional exposures male sex (aOR: 1.1; 95% CI: 1.0-1.2) and the presence of siblings (aOR: 1.3; 95% CI: 1.2-1.4) were associated with the number of infection episodes.<br><br>CONCLUSIONS: This prospective cohort study showed that perinatal factors, mode of delivery and intrapartum antibiotics were not associated with the risk of common infections in infancy, but cesarean delivery was associated with a risk of urinary tract infections.}, }
@article {pmid37750731, year = {2023}, author = {Roche, CE and Montague, MJ and Wang, J and Dickey, AN and Ruiz-Lambides, A and Brent, LJN and Platt, ML and Horvath, JE}, title = {Yearly variation coupled with social interactions shape the skin microbiome in free-ranging rhesus macaques.}, journal = {Microbiology spectrum}, volume = {11}, number = {5}, pages = {e0297423}, pmid = {37750731}, issn = {2165-0497}, support = {R01 MH089484/MH/NIMH NIH HHS/United States ; R01 MH118203/MH/NIMH NIH HHS/United States ; P40 OD012217/OD/NIH HHS/United States ; C06 OD026690/OD/NIH HHS/United States ; R01 MH096875/MH/NIMH NIH HHS/United States ; }, abstract = {While skin microbes are known to mediate human health and disease, there has been minimal research on the interactions between skin microbiota, social behavior, and year-to-year effects in non-human primates-important animal models for translational biomedical research. To examine these relationships, we analyzed skin microbes from 78 rhesus macaques living on Cayo Santiago Island, Puerto Rico. We considered age, sex, and social group membership, and characterized social behavior by assessing dominance rank and patterns of grooming as compared to nonsocial behaviors. To measure the effects of a shifting environment, we sampled skin microbiota (based on sequence analysis of the 16S rRNA V4 region) and assessed weather across sampling periods between 2013 and 2015. We hypothesized that, first, monkeys with similar social behavior and/or in the same social group would possess similar skin microbial composition due, in part, to physical contact, and, second, microbial diversity would differ across sampling periods. We found significant phylum-level differences between social groups in the core microbiome as well as an association between total grooming rates and alpha diversity in the complete microbiome, but no association between microbial diversity and measures of rank or other nonsocial behaviors. We also identified alpha and beta diversity differences in microbiota and differential taxa abundance across two sampling periods. Our findings indicate that social dynamics interact with yearly environmental changes to shape the skin microbiota in rhesus macaques, with potential implications for understanding the factors affecting the microbiome in humans, which share many biological and social characteristics with these animals. IMPORTANCE Primate studies are valuable for translational and evolutionary insights into the human microbiome. The majority of primate microbiome studies focus on the gut, so less is known about the factors impacting the microbes on skin and how their links affect health and behavior. Here, we probe the impact of social interactions and the yearly environmental changes on food-provisioned, free-ranging monkeys living on a small island. We expected animals that lived together and groomed each other would have more similar microbes on their skin, but surprisingly found that the external environment was a stronger influence on skin microbiome composition. These findings have implications for our understanding of the human skin microbiome, including potential manipulations to improve health and treat disease.}, }
@article {pmid37746792, year = {2023}, author = {Fiocchi, A and Monaci, L and De Angelis, E and Calandrelli, V and Dahdah, L and Valluzzi, R and Urbani, S and Mazzuca, C and Arasi, S and Cafarotti, A and Riccardi, C and Artesani, MC and Putignani, L and Pecora, V and Marzano, V and Fierro, V}, title = {Reactivity to allergenic food contaminants: A study on products on the market.}, journal = {Clinical and translational allergy}, volume = {13}, number = {9}, pages = {e12301}, pmid = {37746792}, issn = {2045-7022}, support = {n.a.//Soremartec Italia S.R.L., Alba, Italy/ ; n.a.//Allegria ONLUS, Milan, Italy/ ; }, abstract = {BACKGROUND: The frequency and severity of reactions in food-allergic consumers exposed to unintentional food allergen contamination during production is unknown. To warn allergic consumers, it has been suggested for pre-packaged foods to be precautionary labelled when the food allergen contamination may exceed the amount to which 1%-5% of the population could react (ED01-ED05). ED01 for hazelnut and milk have been estimated at 0.1 and 0.2 mg, respectively, by the Voluntary Incidental Trace Allergen Labelling (VITAL) initiative. The respective reference doses recommended by the FAO/WHO Codex consultation are 3 and 2 mg. We evaluated the reactivity to potential traces of milk and hazelnut allergens in allergen-free pre-packaged products by children affected by severe allergies to milk and hazelnuts.<br><br>METHODS: Oral Food Challenges with commercially available hazelnut-free wafer biscuits and milk-free chocolate pralines were administered to patients with severe food allergies to hazelnut and cow's milk, respectively. Contamination levels of milk or hazelnut allergens were measured using chromatographic separation interfaced with triple quadrupole mass spectrometry.<br><br>RESULTS: No hazelnut allergic patient showed allergic reactions to exposure to biscuits, nor any milk allergic patient displayed allergic reactions to the dark chocolate praline. While no hazelnut trace was detected in biscuits, the praline was found to be contaminated by milk at concentrations ranging between 8 and 35&#xa0;mg total protein/kg food. In our dose model, these amounts exceeded 1.5-10 times the VITAL ED01 and reached the threshold suggested by the FAO/WHO Codex consultation.<br><br>CONCLUSIONS: Upon the consumption of food products available on the market, many patients with severe food allergies tolerate significantly higher doses of allergen than reference doses indicated in the VITAL system used for precautionary allergen labelling. These doses support the safety of the FAO/WHO recommended reference doses.}, }
@article {pmid37745448, year = {2023}, author = {Robertson, EB and Willett, JLE}, title = {Streptococcus mutans inhibits the growth of Enterococcus via the non-ribosomal cyclic peptide mutanobactin.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {37745448}, issn = {2692-8205}, support = {K99 AI151080/AI/NIAID NIH HHS/United States ; }, abstract = {Enterococcus faecalis is a Gram-positive commensal bacterium in the gastrointestinal tract and an opportunistic pathogen. Enterococci are a leading cause of nosocomial infections, treatment of which is complicated by intrinsic and acquired antibiotic resistance mechanisms. Additionally, E. faecalis has been associated with various oral diseases, and it is frequently implicated in the failure of endodontic treatment. For establishment and persistence in a microbial community, E. faecalis must successfully compete against other bacteria. Streptococcal species play an important role in the establishment of the oral microbiome and co-exist with Enterococcus in the small intestine, yet the nature of interactions between E. faecalis and oral streptococci remains unclear. Here, we describe a mechanism by which Streptococcus mutans inhibits the growth of E. faecalis and other Gram-positive pathogens through the production of mutanobactin, a cyclic lipopeptide. Mutanobactin is produced by a polyketide synthase-nonribosomal peptide synthetase hybrid system encoded by the mub locus. Mutanobactin-producing S. mutans inhibits planktonic and biofilm growth of E. faecalis and is also active against other Enterococcus species and Staphylococcus aureus. Mutanobactin damages the cell envelope of E. faecalis, similar to other lipopeptide antibiotics like daptomycin. E. faecalis resistance to mutanobactin is mediated by the virulence factor gelatinase, a secreted metalloprotease. Our results highlight the anti-biofilm potential of the microbial natural product mutanobactin, provide insight into how E. faecalis interacts with other organisms in the human microbiome, and demonstrate the importance of studying E. faecalis dynamics within polymicrobial communities.}, }
@article {pmid37741805, year = {2023}, author = {Wicaksono, WA and Cernava, T and Wassermann, B and Abdelfattah, A and Soto-Giron, MJ and Toledo, GV and Virtanen, SM and Knip, M and Hyöty, H and Berg, G}, title = {The edible plant microbiome: evidence for the occurrence of fruit and vegetable bacteria in the human gut.}, journal = {Gut microbes}, volume = {15}, number = {2}, pages = {2258565}, pmid = {37741805}, issn = {1949-0984}, mesh = {Humans ; Vegetables ; Plants, Edible ; Fruit ; *Gastrointestinal Microbiome/genetics ; *Microbiota ; Bacteria/genetics ; }, abstract = {Diversity of the gut microbiota is crucial for human health. However, whether fruit and vegetable associated bacteria contribute to overall gut bacterial diversity is still unknown. We reconstructed metagenome-assembled genomes from 156 fruit and vegetable metagenomes to investigate the prevalence of associated bacteria in 2,426 publicly available gut metagenomes. The microbiomes of fresh fruits and vegetables and the human gut are represented by members in common such as Enterobacterales, Burkholderiales, and Lactobacillales. Exposure to bacteria via fruit and vegetable consumption potentially has a beneficial impact on the functional diversity of gut microbiota particularly due to the presence of putative health-promoting genes for the production of vitamin and short-chain fatty acids. In the human gut, they were consistently present, although at a low abundance, approx. 2.2%. Host age, vegetable consumption frequency, and the diversity of plants consumed were drivers favoring a higher proportion. Overall, these results provide one of the primary links between the human microbiome and the environmental microbiome. This study revealed evidence that fruit and vegetable-derived microbes could be found in the human gut and contribute to gut microbiome diversity.}, }
@article {pmid37738402, year = {2023}, author = {Cho, H and Qu, Y and Liu, C and Tang, B and Lyu, R and Lin, BM and Roach, J and Azcarate-Peril, MA and Aguiar Ribeiro, A and Love, MI and Divaris, K and Wu, D}, title = {Comprehensive evaluation of methods for differential expression analysis of metatranscriptomics data.}, journal = {Briefings in bioinformatics}, volume = {24}, number = {5}, pages = {}, pmid = {37738402}, issn = {1477-4054}, support = {R01 HG009937/HG/NHGRI NIH HHS/United States ; U01 DE025046/DE/NIDCR NIH HHS/United States ; R03 DE028983/DE/NIDCR NIH HHS/United States ; }, mesh = {Child ; Humans ; Child, Preschool ; *Benchmarking ; Biofilms ; Computer Simulation ; Lactic Acid ; *Stomatognathic Diseases ; }, abstract = {Understanding the function of the human microbiome is important but the development of statistical methods specifically for the microbial gene expression (i.e. metatranscriptomics) is in its infancy. Many currently employed differential expression analysis methods have been designed for different data types and have not been evaluated in metatranscriptomics settings. To address this gap, we undertook a comprehensive evaluation and benchmarking of 10 differential analysis methods for metatranscriptomics data. We used a combination of real and simulated data to evaluate performance (i.e. type I error, false discovery rate and sensitivity) of the following methods: log-normal (LN), logistic-beta (LB), MAST, DESeq2, metagenomeSeq, ANCOM-BC, LEfSe, ALDEx2, Kruskal-Wallis and two-part Kruskal-Wallis. The simulation was informed by supragingival biofilm microbiome data from 300 preschool-age children enrolled in a study of childhood dental disease (early childhood caries, ECC), whereas validations were sought in two additional datasets from the ECC study and an inflammatory bowel disease study. The LB test showed the highest sensitivity in both small and large samples and reasonably controlled type I error. Contrarily, MAST was hampered by inflated type I error. Upon application of the LN and LB tests in the ECC study, we found that genes C8PHV7 and C8PEV7, harbored by the lactate-producing Campylobacter gracilis, had the strongest association with childhood dental disease. This comprehensive model evaluation offers practical guidance for selection of appropriate methods for rigorous analyses of differential expression in metatranscriptomics. Selection of an optimal method increases the possibility of detecting true signals while minimizing the chance of claiming false ones.}, }
@article {pmid37736390, year = {2023}, author = {Dweh, TJ and Pattnaik, S and Sahoo, JP}, title = {Assessing the impact of meta-genomic tools on current cutting-edge genome engineering and technology.}, journal = {International journal of biochemistry and molecular biology}, volume = {14}, number = {4}, pages = {62-75}, pmid = {37736390}, issn = {2152-4114}, abstract = {Metagenomics is defined as the study of the genome of the total microbiota found in nature and is often referred to as microbial environmental genomics because it entails the examination of a group of genetic components (genomes) from a diverse community of organisms in a particular setting. It is a sub-branch of omics technology that encompasses Deoxyribonucleic Acid (DNA), Ribonucleic acid (DNA), proteins, and various components associated with comprehensive analysis of all aspects of biological molecules in a system-wide manner. Clustered regularly interspaced palindromic repeats and its endonuclease, CRISPR-associated protein which forms a complex called CRISPR-cas9 technology, though it is a different technique used to make precise changes to the genome of an organism, it can be used in conjunction with metagenomic approaches to give a better, rapid, and more accurate description of genomes and sequence reads. There have been ongoing improvements in sequencing that have deepened our understanding of microbial genomes forever. From the time when only a small amount of gene could be sequenced using traditional methods (e.g., "the plus and minus" method developed by Allan and Sanger and the "chemical cleavage" method that is known for its use in the sequencing the phiX174 bacteriophage genome via radio-labeled DNA polymerase-primer in a polymerization reaction aided by polyacrylamide gel) to the era of total genomes sequencing which includes "sequencing-by-ligation" and the "sequencing-by-synthesis" that detects hydrogen ions when new DNA is synthesized (Second Generation) and then Next Generation Sequencing technologies (NGS). With these technologies, the Human Genome Project (HGP) was made possible. The study looks at recent advancements in metagenomics in plants and animals by examining findings from randomly selected research papers. All selected case studies examined the functional and taxonomical analysis of different microbial communities using high-throughput sequencing to generate different sequence reads. In animals, five studies indicated how Zebrafish, Livestock, Poultry, cattle, niches, and the human microbiome were exploited using environmental samples, such as soil and water, to identify microbial communities and their functions. It has also been used to study the microbiome of humans and other organisms, including gut microbiomes. Recent studies demonstrated how these technologies have allowed for faster and more accurate identification of pathogens, leading to improved disease diagnostics. They have also enabled the development of personalized medicine by allowing for the identification of genetic variations that can impact drug efficacy and toxicity. Continued advancements in sequencing techniques and the refinement of CRISPR-Cas9 tools offer even greater potential for transformative breakthroughs in scientific research and applications. On the other hand, metagenomic data are always large and uneasy to handle. The complexity of taxonomical profiling, functional annotation, and mechanisms of complex interaction still needs better bioinformatics tools. Current review focuses on better (e.g., AI-driven algorithms) tools that can predict metabolic pathways and interactions, and manipulate complex data to address potential bias for accurate interpretation.}, }
@article {pmid37731926, year = {2023}, author = {Dikareva, E and Matharu, D and Lahtinen, E and Kolho, KL and De Vos, WM and Salonen, A and Ponsero, AJ}, title = {An extended catalog of integrated prophages in the infant and adult fecal microbiome shows high prevalence of lysogeny.}, journal = {Frontiers in microbiology}, volume = {14}, number = {}, pages = {1254535}, pmid = {37731926}, issn = {1664-302X}, abstract = {BACKGROUND AND AIMS: The acquisition and gradual maturation of gut microbial communities during early childhood is central to an individual's healthy development. Bacteriophages have the potential to shape the gut bacterial communities. However, the complex ecological interactions between phages and their bacterial host are still poorly characterized. In this study, we investigated the abundance and diversity of integrated prophages in infant and adult gut bacteria by detecting integrated prophages in metagenome assembled genomes (MAGs) of commensal bacteria.<br><br>METHODS: Our study included 88 infants sampled at 3&#x2009;weeks, 3&#x2009;months, 6&#x2009;months, and 12&#x2009;months (n&#x2009;=&#x2009;323 total samples), and their parents around delivery time (n&#x2009;=&#x2009;138 total samples). Fecal DNA was extracted and characterized by using shotgun metagenomic sequencing, and a collection of prokaryotic MAGs was generated. The MAG collection was screened for the presence of integrated bacteriophage sequences, allowing their taxonomic and functional characterization.<br><br>RESULTS: A large collection of 6,186 MAGs from infant and adult gut microbiota was obtained and screened for integrated prophages, allowing the identification of 7,165 prophage sequences longer than 10&#x2009;kb. Strikingly, more than 70% of the near-complete MAGs were identified as lysogens. The prevalence of prophages in MAGs varied across bacterial families, with a lower prevalence observed among Coriobacteriaceae, Eggerthellaceae, Veillonellaceae and Burkholderiaceae, while a very high prevalence of lysogen MAGs were observed in Oscillospiraceae, Enterococcaceae, and Enterobacteriaceae. Interestingly for several bacterial families such as Bifidobacteriaceae and Bacteroidaceae, the prevalence of prophages in MAGs was higher in early infant time point (3&#x2009;weeks and 3&#x2009;months) than in later sampling points (6 and 12&#x2009;months) and in adults. The prophage sequences were clustered into 5,616 species-like vOTUs, 77% of which were novel. Finally, we explored the functional repertoire of the potential auxiliary metabolic genes carried by these prophages, encoding functions involved in carbohydrate metabolism and degradation, amino acid metabolism and carbon metabolism.<br><br>CONCLUSION: Our study provides an enhanced understanding of the diversity and prevalence of lysogens in infant and adult gut microbiota and suggests a complex interplay between prophages and their bacterial hosts.}, }
@article {pmid37730417, year = {2023}, author = {Li, YQ and Peng, X and Ren, B and Yan, FH and Pan, YP and Chen, F and Du, WB and Liu, JG and Feng, Q and Yang, DQ and Huang, XJ and Pan, YH and Huang, ZZ and Ding, PH and Zhang, KK and Liu, HX and Zhou, XD}, title = {[Standardized nomenclature of oral microorganisms in Chinese: the 2023 update].}, journal = {Zhonghua kou qiang yi xue za zhi = Zhonghua kouqiang yixue zazhi = Chinese journal of stomatology}, volume = {58}, number = {10}, pages = {1051-1061}, doi = {10.3760/cma.j.cn112144-20230816-00079}, pmid = {37730417}, issn = {1002-0098}, abstract = {Oral microbial community, as an important part of human microbial community, is closely related to oral and general health. Oral microbiological research has become the forefront of international microbiological research. Standardized and unified nomenclature for oral microorganisms in Chinese is of great significance to support the development of oral medicine research. Standardized translation of microbial names is the basis for writing canonical and authoritative professional textbooks and reference books, which helps students to accurately acquire the characteristics and classifications of oral microbes. Unified translation of oral microorganisms is also conducive to academic communication and cooperation, and plays an important role in oral health education and science popularization, which enables oral microbiology knowledge to be accurately disseminated to the public. Therefore, in order to standardize the words in scientific research, funding application, publications, academic exchanges and science popularization within the field of oral medicine, we have fully discussed and revised the Chinese names of oral microorganisms in 2017 edition and ones of newly discovered oral microbes, finally reaching a consensus to form the 2023 edition of Chinese names of oral microorganisms.}, }
@article {pmid37722774, year = {2023}, author = {Wang, Y and Jian, C}, title = {Novel plant-based meat alternatives: Implications and opportunities for consumer nutrition and health.}, journal = {Advances in food and nutrition research}, volume = {106}, number = {}, pages = {241-274}, doi = {10.1016/bs.afnr.2023.03.006}, pmid = {37722774}, issn = {1043-4526}, mesh = {Animals ; Humans ; *Nutritional Status ; Meat ; Food Additives ; *Meat Products ; Nutrients ; }, abstract = {Against the backdrop of the global protein transition needed to remain within planetary boundaries, there is an influx of plant-based meat alternatives that seek to approximate the texture, flavor and/or nutrient profiles of conventional animal meat. These novel plant-based meat alternatives, enabled by advances in food technology, can be fundamentally different from the whole-plant foods from which they are derived. One of the reasons is the necessity to use food additives on various occasions, since consumers' acceptance of plant-based meat products primarily depends on the organoleptic properties. Consequently, a high degree of heterogeneity in formulation and nutritional profiles exists both within and between product categories of plant-based meat alternatives with unknown effects on several aspects of human health. This is further complicated by the differences in digestibility and bioavailability between proteins from animal and plant sources, which have a profound impact on colonic fermentation, nutritional adequacy and potential health effects. On the other hand, emerging strategies provide opportunities to develop affordable, delicious and nutritious plant-based meat alternatives that align with consumer interests.}, }
@article {pmid37705730, year = {2023}, author = {Saglam, D and Colak, GA and Sahin, E and Ekren, BY and Sezerman, U and Bas, M}, title = {Effects of Ramadan intermittent fasting on gut microbiome: is the diet key?.}, journal = {Frontiers in microbiology}, volume = {14}, number = {}, pages = {1203205}, pmid = {37705730}, issn = {1664-302X}, abstract = {Much research has been conducted regarding the impact of diet on the gut microbiota. However, the effects of dietary habits such as intermittent fasting are unclear. This study aimed to investigate the effect of intermittent fasting during Ramadan on the gut microbiota. The study was conducted on 12 healthy adult individuals who practiced fasting 17 h per day for 29 consecutive days during the month of Ramadan. To determine the dietary intake of individuals, a 3-day dietary record was kept at the beginning and end of the study. Reads that passed quality filtering were clustered, and custom-prepared 16S rRNA gene regions of bacteria associated with the human microbiome were used as a reference. Consensus sequences were created, and genus-level taxonomic annotations were determined using a sequence identity threshold of 95%. The correlations between the dietary intake measurements of the participants and the respective relative abundance of bacterial genera were investigated. The results showed that Firmicutes were higher in abundance in the gut microbiota before fasting among participants, while they were significantly lower in abundance at the end of Ramadan fasting (p < 0.05). Proteobacteria were significantly higher in abundance at the end of the month of Ramadan (p < 0.05). Fasting was associated with a significant decrease in levels of seven genera: Blautia, Coprococcus, Dorea, Faecalicatena, Fusicatenibacter, Lachnoclostridium, and Mediterraneibacter. Conversely, the abundances of two bacterial genera were enhanced at the end of the fasting month: Escherichia and Shigella. The results of the dietary intake analysis showed that a negative correlation was detected for three comparisons: Ihubacter and protein (rho = -0.54, p = 0.0068), Fusicatenibacter and vegetables (rho = -0.54, p = 0.0042), and Intestinibacter and nuts (rho = -0.54, p-value = 0.0065). The results suggest that even when the fasting period during Ramadan is consistent, the types of food consumed by individuals can affect the gut microbiota.}, }
@article {pmid37705353, year = {2024}, author = {Kobyliak, N and Khomenko, M and Falalyeyeva, T and Fedchenko, A and Savchuk, O and Tseyslyer, Y and Ostapchenko, L}, title = {Probiotics for pancreatic β-cell function: from possible mechanism of action to assessment of effectiveness.}, journal = {Critical reviews in microbiology}, volume = {50}, number = {5}, pages = {663-683}, doi = {10.1080/1040841X.2023.2257776}, pmid = {37705353}, issn = {1549-7828}, mesh = {*Probiotics/pharmacology/therapeutic use ; Humans ; *Insulin-Secreting Cells/metabolism ; *Diabetes Mellitus, Type 2/microbiology ; Animals ; *Gastrointestinal Microbiome ; }, abstract = {Type 2 diabetes (T2D) is a metabolic disease characterized by chronic hyperglycemia because of insulin resistance (IR) and\or pancreatic β-cell dysfunction. Last century research showed that gut microbiota has a direct effect on metabolism and metabolic diseases. New studies into the human microbiome and its connection with the host is making it possible to develop new therapies for a wide variety of diseases. Inflammation is a well-known precursor to metabolic syndrome, which increases the risk of hypertension, visceral obesity, and dyslipidemia, which can lead to T2D through the damage of pancreatic β-cell and reduce insulin secretion. Current understanding for beneficial effects of probiotics in T2D strictly rely on both animal and clinical data, which mostly focused on their impact on IR, anthropometric parameters, glycemic control and markers of chronic systemic inflammation. From the other hand, there is a lack of evidence-based probiotic efficacy on pancreatic β-cell function in terms of T2D and related metabolic disorders. Therefore, current review will focus on the efficacy of probiotics for the protection of β-cells damage and it`s mechanism in patients with T2D.}, }
@article {pmid37700048, year = {2023}, author = {Zuo, T}, title = {Gut bacteriophages ignite mammalian immunity.}, journal = {Nature reviews. Microbiology}, volume = {21}, number = {10}, pages = {634}, pmid = {37700048}, issn = {1740-1534}, }
@article {pmid37699408, year = {2023}, author = {Carvalho, MR and Yan, LP and Li, B and Zhang, CH and He, YL and Reis, RL and Oliveira, JM}, title = {Gastrointestinal organs and organoids-on-a-chip: advances and translation into the clinics.}, journal = {Biofabrication}, volume = {15}, number = {4}, pages = {}, doi = {10.1088/1758-5090/acf8fb}, pmid = {37699408}, issn = {1758-5090}, mesh = {United States ; Humans ; *Microphysiological Systems ; *Gastrointestinal Tract ; Stomach ; Liver ; Organoids ; }, abstract = {Microfluidic organs and organoids-on-a-chip models of human gastrointestinal systems have been established to recreate adequate microenvironments to study physiology and pathophysiology. In the effort to find more emulating systems and less costly models for drugs screening or fundamental studies, gastrointestinal system organoids-on-a-chip have arisen as promising pre-clinicalin vitromodel. This progress has been built on the latest developments of several technologies such as bioprinting, microfluidics, and organoid research. In this review, we will focus on healthy and disease models of: human microbiome-on-a-chip and its rising correlation with gastro pathophysiology; stomach-on-a-chip; liver-on-a-chip; pancreas-on-a-chip; inflammation models, small intestine, colon and colorectal cancer organoids-on-a-chip and multi-organoids-on-a-chip. The current developments related to the design, ability to hold one or more 'organs' and its challenges, microfluidic features, cell sources and whether they are used to test drugs are overviewed herein. Importantly, their contribution in terms of drug development and eminent clinical translation in precision medicine field, Food and Drug Administration approved models, and the impact of organoid-on-chip technology in terms of pharmaceutical research and development costs are also discussed by the authors.}, }
@article {pmid37698033, year = {2023}, author = {Zuo, T and Liang, G and Huang, Z and Cao, Z and Bai, F and Zhou, Y and Wu, X and Wu, X and Chen, YQ and Balati, M and Maimaitiyiming, M and ,  and Lan, P}, title = {Baseline gut microbiome features prior to SARS-CoV-2 infection are associated with host symptoms in and post COVID-19.}, journal = {Journal of medical virology}, volume = {95}, number = {9}, pages = {e29083}, doi = {10.1002/jmv.29083}, pmid = {37698033}, issn = {1096-9071}, mesh = {Humans ; *Gastrointestinal Microbiome ; *COVID-19 ; SARS-CoV-2 ; *Microbiota ; China/epidemiology ; }, abstract = {The human gut microbiome varies substantially across individuals and populations and differentially tames our immunity at steady-state. Hence, we hypothesize that the large heterogeneity of gut microbiomes at steady-state may shape our baseline immunity differentially, and then mediate discrepant immune responses and symptoms when one encounters a viral infection, such as SARS-CoV-2 infection. To validate this hypothesis, we conducted an exploratory, longitudinal microbiome-COVID-19 study involving homogenous young participants from two geographically different regions in China. Subjects were recruited and sampled of fecal specimens before the 3-week surge window of COVID-19 (between December 11 and December 31, 2022) in China, and then were followed up for assessment of COVID-19 and post-COVID-19 manifestations. Our data showed that the baseline gut microbiome composition was intricately associated with different COVID-19 manifestations, particularly gastrointestinal involvement and post-COVID-19 lingering symptoms, in both an individual- and population-dependent manner. Our study intriguingly for the first time highlight that the gut microbiome at steady-state may prepare us differentially for weathering a respiratory viral infection.}, }
@article {pmid37697153, year = {2024}, author = {}, title = {BugSigDB - a database for identifying unusual abundance patterns in human microbiome studies.}, journal = {Nature biotechnology}, volume = {42}, number = {5}, pages = {708-709}, pmid = {37697153}, issn = {1546-1696}, mesh = {Humans ; *Microbiota/genetics ; Databases, Genetic ; Databases, Factual ; }, }
@article {pmid37696680, year = {2024}, author = {Del Chierico, F and Cardile, S and Baldelli, V and Alterio, T and Reddel, S and Bramuzzo, M and Knafelz, D and Lega, S and Bracci, F and Torre, G and Maggiore, G and Putignani, L}, title = {Characterization of the Gut Microbiota and Mycobiota in Italian Pediatric Patients With Primary Sclerosing Cholangitis and Ulcerative Colitis.}, journal = {Inflammatory bowel diseases}, volume = {30}, number = {4}, pages = {529-537}, pmid = {37696680}, issn = {1536-4844}, support = {//Italian Ministry of Health/ ; }, mesh = {Humans ; Child ; *Colitis, Ulcerative/complications ; *Gastrointestinal Microbiome ; *Cholangitis, Sclerosing/complications ; Dysbiosis/microbiology ; RNA, Ribosomal, 16S/genetics ; Bacteria/genetics ; Bacteroidetes ; Italy ; }, abstract = {BACKGROUND: Primary sclerosing cholangitis (PSC) is a chronic, fibroinflammatory, cholestatic liver disease of unknown etiopathogenesis, often associated with inflammatory bowel diseases. Recent evidence ascribes, together with immunologic and environmental components, a significant role to the intestinal microbiota or its molecules in the PSC pathogenesis.<br><br>METHODS: By metagenomic sequencing of 16S rRNA and ITS2 loci, we describe the fecal microbiota and mycobiota of 26 pediatric patients affected by PSC and concomitant ulcerative colitis (PSC-UC), 27 patients without PSC but with UC (UC), and 26 healthy subjects (CTRLs).<br><br>RESULTS: Compared with CTRL, the bacterial and fungal gut dysbiosis was evident for both PSC-UC and UC groups; in particular, Streptococcus, Saccharomyces, Sporobolomyces, Tilletiopsis, and Debaryomyces appeared increased in PSC-UC, whereas Klebsiella, Haemophilus, Enterococcus Collinsella, Piptoporus, Candida, and Hyphodontia in UC. In both patient groups, Akkermansia, Bacteroides, Parabacteroides, Oscillospira, Meyerozyma and Malassezia were decreased. Co-occurrence analysis evidenced the lowest number of nodes and edges for fungi networks compared with bacteria. Finally, we identified a specific patient profile, based on liver function tests, bacterial and fungal signatures, that is able to distinguish PSC-UC from UC patients.<br><br>CONCLUSIONS: We describe the gut microbiota and mycobiota dysbiosis associated to PSC-UC disease. Our results evidenced a gut imbalance, with the reduction of gut commensal microorganisms with stated anti-inflammatory properties (ie, Akkermansia, Bacteroides, Parabacteroides, Oscillospira, Meyerozyma, and Malassezia) and the increase of pathobionts (ie, Streptococcus, Saccharomyces, and Debaryomyces) that could be involved in PSC progression. Altogether, these events may concur in the pathophysiology of PSC in the framework of UC.}, }
@article {pmid37690584, year = {2024}, author = {Borrego-Ruiz, A and Borrego, JJ}, title = {An updated overview on the relationship between human gut microbiome dysbiosis and psychiatric and psychological disorders.}, journal = {Progress in neuro-psychopharmacology &amp; biological psychiatry}, volume = {128}, number = {}, pages = {110861}, doi = {10.1016/j.pnpbp.2023.110861}, pmid = {37690584}, issn = {1878-4216}, abstract = {There is a lot of evidence establishing that nervous system development is related to the composition and functions of the gut microbiome. In addition, the central nervous system (CNS) controls the imbalance of the intestinal microbiota, constituting a bidirectional communication system. At present, various gut-brain crosstalk routes have been described, including immune, endocrine and neural circuits via the vagal pathway. Several empirical data have associated gut microbiota alterations (dysbiosis) with neuropsychiatric diseases, such as Alzheimer's disease, autism and Parkinson's disease, and with other psychological disorders, like anxiety and depression. Fecal microbiota transplantation (FMT) therapy has shown that the gut microbiota can transfer behavioral features to recipient animals, which provides strong evidence to establish a causal-effect relationship. Interventions, based on prebiotics, probiotics or synbiotics, have demonstrated an important influence of microbiota on neurological disorders by the synthesis of neuroactive compounds that interact with the nervous system and by the regulation of inflammatory and endocrine processes. Further research is needed to demonstrate the influence of gut microbiota dysbiosis on psychiatric and psychological disorders, and how microbiota-based interventions may be used as potential therapeutic tools.}, }
@article {pmid37686314, year = {2023}, author = {Santos, FP and Carvalhos, CA and Figueiredo-Dias, M}, title = {New Insights into Photobiomodulation of the Vaginal Microbiome-A Critical Review.}, journal = {International journal of molecular sciences}, volume = {24}, number = {17}, pages = {}, pmid = {37686314}, issn = {1422-0067}, mesh = {Female ; Humans ; Autoimmunity ; Dysbiosis ; *Microbiota ; *Vagina/microbiology ; Low-Level Light Therapy ; }, abstract = {The development of new technologies such as sequencing has greatly enhanced our understanding of the human microbiome. The interactions between the human microbiome and the development of several diseases have been the subject of recent research. In-depth knowledge about the vaginal microbiome (VMB) has shown that dysbiosis is closely related to the development of gynecologic and obstetric disorders. To date, the progress in treating or modulating the VMB has lagged far behind research efforts. Photobiomodulation (PBM) uses low levels of light, usually red or near-infrared, to treat a diversity of conditions. Several studies have demonstrated that PBM can control the microbiome and improve the activity of the immune system. In recent years, increasing attention has been paid to the microbiome, mostly to the gut microbiome and its connections with many diseases, such as metabolic disorders, obesity, cardiovascular disorders, autoimmunity, and neurological disorders. The applicability of PBM therapeutics to treat gut dysbiosis has been studied, with promising results. The possible cellular and molecular effects of PBM on the vaginal microbiome constitute a theoretical and promising field that is starting to take its first steps. In this review, we will discuss the potential mechanisms and effects of photobiomodulation in the VMB.}, }
@article {pmid37685376, year = {2023}, author = {Unal, M and Bostanci, E and Ozkul, C and Acici, K and Asuroglu, T and Guzel, MS}, title = {Crohn's Disease Prediction Using Sequence Based Machine Learning Analysis of Human Microbiome.}, journal = {Diagnostics (Basel, Switzerland)}, volume = {13}, number = {17}, pages = {}, pmid = {37685376}, issn = {2075-4418}, abstract = {Human microbiota refers to the trillions of microorganisms that inhabit our bodies and have been discovered to have a substantial impact on human health and disease. By sampling the microbiota, it is possible to generate massive quantities of data for analysis using Machine Learning algorithms. In this study, we employed several modern Machine Learning techniques to predict Inflammatory Bowel Disease using raw sequence data. The dataset was obtained from NCBI preprocessed graph representations and converted into a structured form. Seven well-known Machine Learning frameworks, including Random Forest, Support Vector Machines, Extreme Gradient Boosting, Light Gradient Boosting Machine, Gaussian Naïve Bayes, Logistic Regression, and k-Nearest Neighbor, were used. Grid Search was employed for hyperparameter optimization. The performance of the Machine Learning models was evaluated using various metrics such as accuracy, precision, fscore, kappa, and area under the receiver operating characteristic curve. Additionally, Mc Nemar's test was conducted to assess the statistical significance of the experiment. The data was constructed using k-mer lengths of 3, 4 and 5. The Light Gradient Boosting Machine model overperformed over other models with 67.24%, 74.63% and 76.47% accuracy for k-mer lengths of 3, 4 and 5, respectively. The LightGBM model also demonstrated the best performance in each metric. The study showed promising results predicting disease from raw sequence data. Finally, Mc Nemar's test results found statistically significant differences between different Machine Learning approaches.}, }
@article {pmid37682568, year = {2023}, author = {Moir, J and Hyman, M and Wang, J and Flores, A and Skondra, D}, title = {The Association of Antibiotic Use and the Odds of a New-Onset ICD Code Diagnosis of Age-Related Macular Degeneration: A Large National Case-Control Study.}, journal = {Investigative ophthalmology &amp; visual science}, volume = {64}, number = {12}, pages = {14}, pmid = {37682568}, issn = {1552-5783}, mesh = {Humans ; *Anti-Bacterial Agents/adverse effects ; International Classification of Diseases ; Case-Control Studies ; Prospective Studies ; Aminoglycosides ; Fluoroquinolones ; *Macular Degeneration/diagnosis/epidemiology ; }, abstract = {PURPOSE: The widespread use of antibiotics has many well-documented impacts on the human microbiome, which may be associated with the development of various inflammatory diseases. Despite age-related macular degeneration (AMD) featuring an inflammatory pathogenesis, the relationship between antibiotics and AMD has remained unexplored. We conducted the first study to determine the association between antibiotic exposure and a new-onset International Classification of Diseases (ICD) diagnosis of AMD.<br><br>METHODS: We performed a case-control analysis of patients aged 55 and older with new-onset AMD between 2008 and 2017 from a nationwide commercial health insurance claims database. Exposure to antibiotics in the two years before the index date was determined for cases and controls matched one-to-one by age, year, region, anemia, hypertension, and a comorbidity index. Conditional multivariable logistic regression, adjusted for AMD risk factors, was performed to calculate odd ratios (OR) and 95% confidence intervals (CI).<br><br>RESULTS: Among the antibiotic classes, exposure to aminoglycosides (OR = 1.24; 95% CI, 1.22-1.26) and fluoroquinolones (OR = 1.13; 95% CI, 1.12-1.14) was associated with the greatest odds of a new-onset ICD code diagnosis of AMD. Broad-spectrum antibiotics were associated with nearly three times greater odds of a new-onset ICD code diagnosis of AMD (OR = 1.15; 95% CI, 1.13-1.16) compared to narrow-spectrum antibiotics (OR = 1.05; 95% CI, 1.03-1.07). We also identified a frequency- and duration-dependent association, with a greater cumulative number of antibiotic prescriptions or day supply of antibiotics conferring increased odds of a new-onset ICD code diagnosis of AMD.<br><br>CONCLUSIONS: Greater cumulative exposure to antibiotics, particularly fluoroquinolones, aminoglycosides, and those with broader-spectrum coverage, may be associated with the development of AMD, a finding that requires further investigation using prospective studies.}, }
@article {pmid37671026, year = {2023}, author = {Pietiäinen, V and Polso, M and Migh, E and Guckelsberger, C and Harmati, M and Diosdi, A and Turunen, L and Hassinen, A and Potdar, S and Koponen, A and Sebestyen, EG and Kovacs, F and Kriston, A and Hollandi, R and Burian, K and Terhes, G and Visnyovszki, A and Fodor, E and Lacza, Z and Kantele, A and Kolehmainen, P and Kakkola, L and Strandin, T and Levanov, L and Kallioniemi, O and Kemeny, L and Julkunen, I and Vapalahti, O and Buzas, K and Paavolainen, L and Horvath, P and Hepojoki, J}, title = {Image-based and machine learning-guided multiplexed serology test for SARS-CoV-2.}, journal = {Cell reports methods}, volume = {3}, number = {8}, pages = {100565}, pmid = {37671026}, issn = {2667-2375}, mesh = {Humans ; *SARS-CoV-2 ; *COVID-19 ; COVID-19 Testing ; Acclimatization ; Machine Learning ; }, abstract = {We present a miniaturized immunofluorescence assay (mini-IFA) for measuring antibody response in patient blood samples. The method utilizes machine learning-guided image analysis and enables simultaneous measurement of immunoglobulin M (IgM), IgA, and IgG responses against different viral antigens in an automated and high-throughput manner. The assay relies on antigens expressed through transfection, enabling use at a low biosafety level and fast adaptation to emerging pathogens. Using severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) as the model pathogen, we demonstrate that this method allows differentiation between vaccine-induced and infection-induced antibody responses. Additionally, we established a dedicated web page for quantitative visualization of sample-specific results and their distribution, comparing them with controls and other samples. Our results provide a proof of concept for the approach, demonstrating fast and accurate measurement of antibody responses in a research setup with prospects for clinical diagnostics.}, }
@article {pmid37669300, year = {2023}, author = {Casulli, A and Pane, S and Randi, F and Scaramozzino, P and Carvelli, A and Marras, CE and Carai, A and Santoro, A and Santolamazza, F and Tamarozzi, F and Putignani, L}, title = {Primary cerebral cystic echinococcosis in a child from Roman countryside: Source attribution and scoping review of cases from the literature.}, journal = {PLoS neglected tropical diseases}, volume = {17}, number = {9}, pages = {e0011612}, pmid = {37669300}, issn = {1935-2735}, mesh = {Humans ; Child ; Animals ; Sheep ; Young Adult ; Adult ; *Echinococcosis ; *Cysticercosis ; *Central Nervous System Parasitic Infections ; Zoonoses ; *Cysts ; Larva ; }, abstract = {BACKGROUND: Human cystic echinococcosis (CE) is a zoonotic parasitic infection caused by the larval stage of the species belonging to the Echinococcus granulosus sensu lato (s.l.) complex. Parasitic cysts causing human CE are mainly localized in the liver and in the lungs. In a smaller number of cases, larvae may establish in any organ or tissue, including the central nervous system (CNS). Cerebral CE (CCE) is rare but poses serious clinical challenges.<br><br>METHODS: This study presents a case of CCE in a child living in the countryside near Rome (Italy), along with a comparative molecular analysis of the isolated cyst specimens from the patient and sheep of local farms. We also systematically searched the literature to summarize the most relevant epidemiological and clinical aspects of this uncommon localization.<br><br>FINDINGS: The comparative molecular analysis confirmed that the infection was caused by E. granulosus sensu stricto (s.s.) (G3 genotype), and most likely acquired in the family farm. The literature search identified 2,238 cases of CCE. In 80.51% of cases, brain was the only localization and single CCE cysts were present in 84.07% of cases. Mean patients' age was 20 years and 70.46% were children. Cyst rupture was reported in 12.96% and recurrence of CCE after treatment in 9.61% of cases. Permanent disability was reported in 7.86% of cases, while death occurred in 6.21%. In case series reporting all CE localization, CCE represented 1.5% of all CE cases. In the few reports that identified at molecular level the CCE cyst, E. granulosus s.s. was found in 40% and E. canadensis in 60% of cases.<br><br>CONCLUSIONS: We report a rare case of CCE and evidenced the probable local origin of infection. The proportions of CE cases with uncommon localizations and with high impact on patients' lives have been globally neglected and should be included in the computation of the global burden of CE.}, }
@article {pmid37657351, year = {2023}, author = {Toyomane, K and Akutsu, T and Watanabe, K and Yamagishi, T and Kubota, S}, title = {Potential application of Staphylococcus species detection in the specific identification of saliva.}, journal = {Legal medicine (Tokyo, Japan)}, volume = {65}, number = {}, pages = {102320}, doi = {10.1016/j.legalmed.2023.102320}, pmid = {37657351}, issn = {1873-4162}, mesh = {Humans ; *Saliva ; *Staphylococcus/genetics ; RNA, Ribosomal, 16S/genetics ; Bacteria/genetics ; Polymerase Chain Reaction ; }, abstract = {When found at crime scenes, saliva constitutes forensically relevant evidence. Although several tests have been developed to effectively identify saliva in such circumstances, most cannot discriminate between saliva and nasal secretion. Recently, studies have developed saliva tests involving oral bacteria as salivary markers. Although the specificity of such tests has been evaluated on most biological specimens, their specificity for nasal secretion samples remains to be tested. Herein, to improve the specificity of the saliva detection tests for nasal secretion samples, we reanalyzed a public microbiome dataset and conducted inhouse 16S rRNA sequencing to identify a new marker to distinguish between saliva and nasal secretions. The sequencing data indicated the existence of oral bacteria such as Streptococcus in nasal secretion samples, which may be responsible for the false positives in the saliva tests. Furthermore, we found that including the 16S rRNA gene of the genus Staphylococcus as a nasal secretion marker may improve the specificity of PCR-based saliva tests for nasal secretion samples. In addition, we assessed the specificity of previously developed salivary bacteria detection tests for nasal secretion samples and oral bacterial markers were detected in two of eight nasal secretion samples, which led to the false positive results for saliva detection. Thus, the specificity of such tests can be improved by adding Staphylococcus as a nasal marker, as revealed by our sequencing analysis.}, }
@article {pmid37656392, year = {2023}, author = {Rahman, SO and Bariguian, F and Mobasheri, A}, title = {The Potential Role of Probiotics in the Management of Osteoarthritis Pain: Current Status and Future Prospects.}, journal = {Current rheumatology reports}, volume = {25}, number = {12}, pages = {307-326}, pmid = {37656392}, issn = {1534-6307}, mesh = {Humans ; Lipopolysaccharides ; *Osteoarthritis/complications/therapy ; Pain ; *Probiotics/therapeutic use ; Arthralgia ; }, abstract = {PURPOSE OF REVIEW: This narrative review article comprehensively explains the pathophysiology of osteoarthritis (OA) pain perception, how the gut microbiota is correlated with it, possible molecular pathways involved in probiotics-mediated OA pain reduction, limitations in the current research approaches, and future perspectives.<br><br>RECENT FINDINGS: The initiation and progression of OA, including the development of chronic pain, is intricately associated with activation of the innate immune system and subsequent inflammatory responses. Trauma, lifestyle (e.g., obesity and metabolic disease), and chronic antibiotic treatment can disrupt commensal homeostasis of the human microbiome, thereby affecting intestinal integrity and promoting leakage of bacterial endotoxins and metabolites such as lipopolysaccharides (LPS) into circulation. Increased level of LPS is associated with knee osteophyte severity and joint pain. Both preclinical and clinical studies strongly suggest that probiotics may benefit patients with OA pain through positive gut microbiota modulation and attenuating low-grade inflammation via multiple pathways. Patent data also suggests increased interest in the development of new innovations that involve probiotic use for reducing OA and joint pain. Recent data suggest that probiotics are attracting more and more attention for OA pain management. The advancement of knowledge in this area may pave the way for developing different probiotic strains that can be used to support joint health, improve treatment outcomes in OA, and reduce the huge impact of the disease on healthcare systems worldwide.}, }
@article {pmid37655878, year = {2023}, author = {Cauwenberghs, E and Oerlemans, E and Wittouck, S and Allonsius, CN and Gehrmann, T and Ahannach, S and De Boeck, I and Spacova, I and Bron, PA and Donders, G and Verhoeven, V and Lebeer, S}, title = {Salivary microbiome of healthy women of reproductive age.}, journal = {mBio}, volume = {14}, number = {5}, pages = {e0030023}, pmid = {37655878}, issn = {2150-7511}, support = {//Interuniversitair Bijzonder Onderzoeksfonds/ ; 26850//EC | European Research Council (ERC)/ ; 12S4222N, 1277222N//Fonds Wetenschappelijk Onderzoek (FWO)/ ; 37054//Interuniversitair Bijzonder Onderzoeksfonds/ ; }, mesh = {Humans ; Female ; *Reproduction ; Saliva ; Sexual Partners ; *Microbiota ; Health Status ; RNA, Ribosomal, 16S ; }, abstract = {The salivary microbiome has been proven to play a crucial role in local and systemic diseases. Moreover, the effects of biological and lifestyle factors such as oral hygiene and smoking on this microbial community have already been explored. However, what was not yet well understood was the natural variation of the saliva microbiome in healthy women and how this is associated with specific use of hormonal contraception and with the number of different sexual partners with whom microbiome exchange is expected regularly. In this paper, we characterized the salivary microbiome of 255 healthy women of reproductive age using an in-depth questionnaire and self-sampling kits. Using the large metadata set, we were able to investigate the associations of several host-related and lifestyle variables with the salivary microbiome profiles. Our study shows a high preservation between individuals.}, }
@article {pmid37650878, year = {2023}, author = {Lahtinen, MH and Kynkäänniemi, E and Jian, C and Salonen, A and Pajari, AM and Mikkonen, KS}, title = {Metabolic Fate of Lignin in Birch Glucuronoxylan Extracts as Dietary Fiber Studied in a Rat Model.}, journal = {Molecular nutrition &amp; food research}, volume = {67}, number = {20}, pages = {e2300201}, doi = {10.1002/mnfr.202300201}, pmid = {37650878}, issn = {1613-4133}, mesh = {Rats ; Animals ; *Lignin/chemistry/metabolism ; *Betula/metabolism ; Dietary Fiber ; Xylans ; }, abstract = {SCOPE: While previously considered inert, recent studies suggest lignin metabolism with unknown metabolic fates is occurring in the gastrointestinal tract of several animal models. This study focuses on analyzing the potential metabolites of lignin.<br><br>METHODS AND RESULTS: The diets of rats include relatively pure birch glucuronoxylan (pureGX) with residual lignin or lignin-rich GX (GXpoly) in their diet. Nuclear magnetic spectroscopy of the lignin isolated from the GXpoly-fed rats fecal sample shows high alteration in chemical structure, whereas lignin-carbohydrate complexes (LCCs) are enriched in fecal samples from the pureGX group. Moreover, the increased syringyl-to-guaiacyl (S/G) ratio suggests that lignin G-units are predominantly metabolized based on pyrolysis gas chromatography-mass spectrometry (pyr-GC/MS). The presence of small phenolic metabolites identified in urine samples of the GXpoly group, for example, ferulic and sinapic acids, their sulfate and glucuronide derivatives, and 4-sulfobenzylalcohol, suggests that the small fragmented lignin metabolites in the large intestine enter the plasma, and are further processed in the liver. Finally, the relative abundances of polyphenol-degrading Enterorhabdus and Akkermansia in the gut microbiota are associated with lignin metabolism.<br><br>CONCLUSION: These findings give further evidence to lignin metabolism in the gut of nonruminants and provide insight to the potential microbes and metabolic routes.}, }
@article {pmid37644161, year = {2023}, author = {Koo, H and Morrow, CD}, title = {Identification of donor Bacteroides vulgatus genes encoding proteins that correlate with early colonization following fecal transplant of patients with recurrent Clostridium difficile.}, journal = {Scientific reports}, volume = {13}, number = {1}, pages = {14112}, pmid = {37644161}, issn = {2045-2322}, mesh = {Child ; Humans ; Animals ; Mice ; *Fecal Microbiota Transplantation ; *Clostridioides difficile/genetics ; Tissue Donors ; Bacteroides/genetics ; }, abstract = {Due to suppressive antibiotics, patients with recurrent Clostridium difficile have gut microbial communities that are devoid of most commensal microbes. Studies have shown that most of the failures using fecal microbe transplantation (FMT) for recurrent C. difficile occur during the first 4 weeks following transplantation. To identify features of donor Bacteroides vulgatus that lead to early colonization, we used two data sets that collected fecal samples from recipients at early times points post FMT. The first analysis used the shotgun metagenomic DNA sequencing data set from Aggarwala et al. consisting of 7 FMT donors and 13 patients with recurrent C. difficile with fecal samples taken as early as 24 h post FMT. We identified 2 FMT donors in which colonization of recipients by donor B. vulgatus was detected as early as 24 h post FMT. We examined a second data set from Hourigan et al. that collected fecal samples from C. difficile infected children and identified 1 of 3 FMT that also had early colonization of the donor B. vulgatus. We found 19 genes out of 4911 encoding proteins were unique to the 3 donors that had early colonization. A gene encoding a putative chitobiase was identified that was in a gene complex that had been previously identified to enhance colonization in mice. A gene encoding a unique fimbrillin (i.e., pili) family protein and 17 genes encoding hypothetical proteins were also specific for early colonizing donors. Most of the genes encoding hypothetical proteins had neighboring genes that encoded proteins involved in mobilization or transposition. Finally, analysis of 42 paired fecal samples from the human microbiome project (HMP) found no individuals had all 19 genes while 2 individuals had none of the 19 genes. Based on the results from our study, consideration should be given to the screening of FMT donors for these B. vulgatus genes found to enhance early colonization that would be of benefit to promote colonization following FMT.}, }
@article {pmid37642431, year = {2023}, author = {Farmer, N and Maki, KA and Barb, JJ and Jones, KK and Yang, L and Baumer, Y and Powell-Wiley, TM and Wallen, GR}, title = {Geographic social vulnerability is associated with the alpha diversity of the human microbiome.}, journal = {mSystems}, volume = {8}, number = {5}, pages = {e0130822}, pmid = {37642431}, issn = {2379-5077}, mesh = {Humans ; *Social Vulnerability ; *Microbiota/genetics ; Geography ; Risk Factors ; Public Health ; }, abstract = {As a risk factor for conditions related to the microbiome, understanding the role of SVI on microbiome diversity may assist in identifying public health implications for microbiome research. Here we found, using a sub-sample of the Human Microbiome Project phase 1 cohort, that SVI was linked to microbiome diversity across body sites and that SVI may influence race/ethnicity-based differences in diversity. Our findings, build on the current knowledge regarding the role of human geography in microbiome research, suggest that measures of geographic social vulnerability be considered as additional contextual factors when exploring microbiome alpha diversity.}, }
@article {pmid37637212, year = {2023}, author = {Li, W and Mirone, J and Prasad, A and Miolane, N and Legrand, C and Dao Duc, K}, title = {Orthogonal outlier detection and dimension estimation for improved MDS embedding of biological datasets.}, journal = {Frontiers in bioinformatics}, volume = {3}, number = {}, pages = {1211819}, pmid = {37637212}, issn = {2673-7647}, abstract = {Conventional dimensionality reduction methods like Multidimensional Scaling (MDS) are sensitive to the presence of orthogonal outliers, leading to significant defects in the embedding. We introduce a robust MDS method, called DeCOr-MDS (Detection and Correction of Orthogonal outliers using MDS), based on the geometry and statistics of simplices formed by data points, that allows to detect orthogonal outliers and subsequently reduce dimensionality. We validate our methods using synthetic datasets, and further show how it can be applied to a variety of large real biological datasets, including cancer image cell data, human microbiome project data and single cell RNA sequencing data, to address the task of data cleaning and visualization.}, }
@article {pmid37630623, year = {2023}, author = {Cho, YJ and Shin, B and Lee, SH and Park, S and Kim, YK and Kim, JJ and Kim, E}, title = {Altered Urine Microbiome in Male Children and Adolescents with Attention-Deficit Hyperactivity Disorder.}, journal = {Microorganisms}, volume = {11}, number = {8}, pages = {}, pmid = {37630623}, issn = {2076-2607}, support = {6-2019-0174//Yonsei University, College of Medicine/ ; }, abstract = {While interest in developing the human microbiome as a biomarker for attention-deficit hyperactivity disorder (ADHD) is increasing, there has been limited exploration in utilizing urine samples. In this study, we analysed urine microbiome profiles by extracting 16S ribosomal DNA from purified bacteria-derived extracellular membrane vesicles obtained from urine samples. Sequencing libraries were constructed by amplifying V3-V4 hypervariable regions sequenced using Illumina MiSeq. Profiles of male Korean children and adolescents with ADHD (n = 33) were compared with healthy sex-matched controls (n = 39). Statistically controlling for age, we found decreased alpha diversity in the urine bacteria of the ADHD group, as evidenced by reduced Shannon and Simpson indices (p < 0.05), and significant differences in beta diversity between the two groups (p < 0.001). The phyla Firmicutes and Actinobacteriota, as well as the genera Ralstonia and Afipia, were relatively more abundant in the ADHD group. The phylum Proteobacteria and the genera Corynebacterium and Peptoniphilus were more abundant in the control group. Notably, the genus Afipia exhibited significant correlations with the Child Behavior Checklist Attention Problems score and DSM-oriented ADHD subscale. This study is the first to propose the urine microbiome as a potential biomarker for pediatric ADHD.}, }
@article {pmid37627516, year = {2023}, author = {Torreggiani, A and Demarinis, C and Pinto, D and Papale, A and Difonzo, G and Caponio, F and Pontonio, E and Verni, M and Rizzello, CG}, title = {Up-Cycling Grape Pomace through Sourdough Fermentation: Characterization of Phenolic Compounds, Antioxidant Activity, and Anti-Inflammatory Potential.}, journal = {Antioxidants (Basel, Switzerland)}, volume = {12}, number = {8}, pages = {}, pmid = {37627516}, issn = {2076-3921}, abstract = {Despite its appealing composition, because it is rich in fibers and polyphenols, grape pomace, the major by-product of the wine industry, is still discarded or used for feed. This study aimed at exploiting grape pomace functional potential through fermentation with lactic acid bacteria (LAB). A systematic approach, including the progressively optimization of the grape pomace substrate, was used, evaluating pomace percentage, pH, and supplementation of nitrogen and carbon sources. When grape pomace was used at 10%, especially without pH correction, LAB cell viability decreased up to 2 log cycles. Hence, the percentage was lowered to 5 or 2.5% and supplementations with carbon and nitrogen sources, which are crucial for LAB metabolism, were considered aiming at obtaining a proper fermentation of the substrate. The optimization of the substrate enabled the comparison of strains performances and allowed the selection of the best performing strain (Lactiplantibacillus plantarum T0A10). A sourdough, containing 5% of grape pomace and fermented with the selected strain, showed high antioxidant activity on DPPH and ABTS radicals and anti-inflammatory potential on Caco2 cells. The anthocyanins profile of the grape pomace sourdough was also characterized, showing qualitative and quantitative differences before and after fermentation. Overall, the grape pomace sourdough showed promising applications as a functional ingredient in bread making.}, }
@article {pmid37627114, year = {2023}, author = {Miya, TV and Marima, R and Damane, BP and Ledet, EM and Dlamini, Z}, title = {Dissecting Microbiome-Derived SCFAs in Prostate Cancer: Analyzing Gut Microbiota, Racial Disparities, and Epigenetic Mechanisms.}, journal = {Cancers}, volume = {15}, number = {16}, pages = {}, pmid = {37627114}, issn = {2072-6694}, support = {23108//South African Medical Research Council/ ; 138139//National Research Foundation/ ; }, abstract = {Prostate cancer (PCa) continues to be the most diagnosed cancer and the second primary cause of fatalities in men globally. There is an abundance of scientific evidence suggesting that the human microbiome, together with its metabolites, plays a crucial role in carcinogenesis and has a significant impact on the efficacy of anticancer interventions in solid and hematological cancers. These anticancer interventions include chemotherapy, immune checkpoint inhibitors, and targeted therapies. Furthermore, the microbiome can influence systemic and local immune responses using numerous metabolites such as short-chain fatty acids (SCFAs). Despite the lack of scientific data in terms of the role of SCFAs in PCa pathogenesis, recent studies show that SCFAs have a profound impact on PCa progression. Several studies have reported racial/ethnic disparities in terms of bacterial content in the gut microbiome and SCFA composition. These studies explored microbiome and SCFA racial/ethnic disparities in cancers such as colorectal, colon, cervical, breast, and endometrial cancer. Notably, there are currently no published studies exploring microbiome/SCFA composition racial disparities and their role in PCa carcinogenesis. This review discusses the potential role of the microbiome in PCa development and progression. The involvement of microbiome-derived SCFAs in facilitating PCa carcinogenesis and their effect on PCa therapeutic response, particularly immunotherapy, are discussed. Racial/ethnic differences in microbiome composition and SCFA content in various cancers are also discussed. Lastly, the effects of SCFAs on PCa progression via epigenetic modifications is also discussed.}, }
@article {pmid37619924, year = {2023}, author = {Golovko, G and Khanipov, K and Reyes, V and Pinchuk, I and Fofanov, Y}, title = {Identification of multivariable Boolean patterns in microbiome and microbial gene composition data.}, journal = {Bio Systems}, volume = {233}, number = {}, pages = {105007}, doi = {10.1016/j.biosystems.2023.105007}, pmid = {37619924}, issn = {1872-8324}, abstract = {Virtually every biological system is governed by complex relations among its components. Identifying such relations requires a rigorous or heuristics-based search for patterns among variables/features of a system. Various algorithms have been developed to identify two-dimensional (involving two variables) patterns employing correlation, covariation, mutual information, etc. It seems obvious, however, that comprehensive descriptions of complex biological systems need also to include more complicated multivariable relations, which can only be described using patterns that simultaneously embrace 3, 4, and more variables. The goal of this manuscript is to (a) introduce a novel type of associations (multivariable Boolean patterns) that can be manifested between features of complex systems but cannot be identified (described) by traditional pair-vise metrics; (b) propose patterns classification method, and (c) provide a novel definition of the pattern's strength (pattern's score) able to accommodate heterogeneous multi-omics data. To demonstrate the presence of such patterns, we performed a search for all possible 2-, 3-, and 4-dimensional patterns in historical data from the Human Microbiome Project (15 body sites) and collection of H. pylori genomes associated with gastric ulcers, gastritis, and duodenal ulcers. In all datasets under consideration, we were able to identify hundreds of statistically significant multivariable patterns. These results suggest that such patterns can be common in microbial genomics/microbiomics systems.}, }
@article {pmid37609252, year = {2023}, author = {Hsu, TY and Nzabarushimana, E and Wong, D and Luo, C and Beiko, RG and Langille, M and Huttenhower, C and Nguyen, LH and Franzosa, EA}, title = {Profiling novel lateral gene transfer events in the human microbiome.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {37609252}, issn = {2692-8205}, support = {K23 DK125838/DK/NIDDK NIH HHS/United States ; R24 DK110499/DK/NIDDK NIH HHS/United States ; U54 DE023798/DE/NIDCR NIH HHS/United States ; }, abstract = {Lateral gene transfer (LGT) is an important mechanism for genome diversification in microbial populations, including the human microbiome. While prior work has surveyed LGT events in human-associated microbial isolate genomes, the scope and dynamics of novel LGT events arising in personal microbiomes are not well understood, as there are no widely adopted computational methods to detect, quantify, and characterize LGT from complex microbial communities. We addressed this by developing, benchmarking, and experimentally validating a computational method (WAAFLE) to profile novel LGT events from assembled metagenomes. Applying WAAFLE to >2K human metagenomes from diverse body sites, we identified >100K putative high-confidence but previously uncharacterized LGT events (~2 per assembled microbial genome-equivalent). These events were enriched for mobile elements (as expected), as well as restriction-modification and transport functions typically associated with the destruction of foreign DNA. LGT frequency was quantifiably influenced by biogeography, the phylogenetic similarity of the involved taxa, and the ecological abundance of the donor taxon. These forces manifest as LGT networks in which hub species abundant in a community type donate unequally with their close phylogenetic neighbors. Our findings suggest that LGT may be a more ubiquitous process in the human microbiome than previously described. The open-source WAAFLE implementation, documentation, and data from this work are available at http://huttenhower.sph.harvard.edu/waafle.}, }
@article {pmid37607643, year = {2023}, author = {Kloepfer, KM and Kennedy, JL}, title = {Childhood respiratory viral infections and the microbiome.}, journal = {The Journal of allergy and clinical immunology}, volume = {152}, number = {4}, pages = {827-834}, pmid = {37607643}, issn = {1097-6825}, support = {U19 AI070535/AI/NIAID NIH HHS/United States ; U01 AI143514/AI/NIAID NIH HHS/United States ; R21 AI154127/AI/NIAID NIH HHS/United States ; U01 AI126614/AI/NIAID NIH HHS/United States ; R21 AI156446/AI/NIAID NIH HHS/United States ; P01 HL158507/HL/NHLBI NIH HHS/United States ; U01 AI179563/AI/NIAID NIH HHS/United States ; P01 HL114471/HL/NHLBI NIH HHS/United States ; R01 HL137192/HL/NHLBI NIH HHS/United States ; }, mesh = {Child ; Humans ; *Microbiota ; *Virus Diseases ; *Asthma ; Lung/microbiology ; Bacteria ; *Viruses ; }, abstract = {The human microbiome associated with the respiratory tract is diverse, heterogeneous, and dynamic. The diversity and complexity of the microbiome and the interactions between microorganisms, host cells, and the host immune system are complex and multifactorial. Furthermore, the lymphatics provide a direct highway, the gut-lung axis, for the gut microbiome to affect outcomes related to respiratory disease and the host immune response. Viral infections in the airways can also alter the presence or absence of bacterial species, which might increase the risks for allergies and asthma. Viruses infect the airway epithelium and interact with the host to promote inflammatory responses that can trigger a wheezing illness. This immune response may alter the host's immune response to microbes and allergens, leading to T2 inflammation. However, exposure to specific bacteria may also tailor the host's response long before the virus has infected the airway. The frequency of viral infections, age at infection, sampling season, geographic location, population differences, and preexisting composition of the microbiota have all been linked to changes in microbiota diversity and stability. This review aims to evaluate the current reported evidence for microbiome interactions and the influences that viral infection may have on respiratory and gut microbiota, affecting respiratory outcomes in children.}, }
@article {pmid37607064, year = {2023}, author = {Wan, KH and Park, S and Booth, BW and Brydon, EC and Eichenberger, J and Inman, JL and Mao, JH and Snijders, AM and Celniker, SE}, title = {Complete genome sequence of the Microbacterium sp. strain BDGP8.}, journal = {Microbiology resource announcements}, volume = {12}, number = {9}, pages = {e0038423}, pmid = {37607064}, issn = {2576-098X}, support = {U.S. Department of Energy Contract No. DE-AC02-05CH11231//DNI | Intelligence Advanced Research Projects Activity (IARPA)/ ; }, abstract = {Microbacterium sp. BDGP8 is a species of facultative anaerobic gram-positive bacterium of the family Microbacteriaceae. The complete genome consists of a single circular chromosome of 3,293,567 bp with a G + C content of 69.84% and two plasmids of 49,365 bp and 32,884 bp.}, }
@article {pmid37603700, year = {2023}, author = {Singh, A and Amod, A and Mulpuru, V and Mishra, N and Sahoo, AK and Samanta, SK}, title = {Finding Novel AMPs Secreted from the Human Microbiome as Potent Antibacterial and Antibiofilm Agents and Studying Their Synergistic Activity with Ag NCs.}, journal = {ACS applied bio materials}, volume = {6}, number = {9}, pages = {3674-3682}, doi = {10.1021/acsabm.3c00302}, pmid = {37603700}, issn = {2576-6422}, mesh = {Humans ; *Antimicrobial Peptides ; Biological Transport ; Anti-Bacterial Agents/pharmacology ; *Microbiota ; Biofilms ; }, abstract = {Due to the enhanced resistance of bacteria to antibiotics, researchers always try to find effective alternatives to treat drug-resistant bacterial infections. In this context, we have explored antimicrobial peptides (AMPs), which are a broad class of small peptide molecules, and investigated their efficacy as potent antibacterial and antibiofilm agents. AMPs can cause cell death either through disruption of the cell membrane or by inhibiting vital intracellular functions, by binding to RNA, DNA, or intracellular components upon transversion through the cell membrane. We attempted to find potent intracellular cationic AMPs that can demonstrate antibacterial activity through interaction with DNA. As a source of AMPs, we have utilized those that are secreted from the human microbiome with the anticipation that these will be non-toxic in nature. Out of the total 1087 AMPs, 27 were screened on the basis of amino acid length and efficacy to cross the cell membrane barrier. From the list of 27 peptides, 4 candidates were selected through the docking score of these peptides with the DNA binding domain of H2A proteins. Further, the molecular dynamics simulation analysis demonstrated that 2 AMPs, i.e., peptides 7 and 25, are having considerable membrane permeation and DNA binding ability. Further, the in vitro analysis indicated that both peptides 7 and 25 could exhibit potent antibacterial and antibiofilm activities. In order to further enhance the antibiofilm potency, the above AMPs were used as supplements to silver nanoclusters (Ag NCs) to get synergistic activity. The synergistic activity of Ag NCs was found to be significantly increased with both the above AMPs.}, }
@article {pmid37603579, year = {2023}, author = {Liu, Y and Zhang, YZ and Imoto, S}, title = {Microbial Gene Ontology informed deep neural network for microbe functionality discovery in human diseases.}, journal = {PloS one}, volume = {18}, number = {8}, pages = {e0290307}, pmid = {37603579}, issn = {1932-6203}, mesh = {Humans ; *Genes, Microbial ; Benchmarking ; Gene Ontology ; *Inflammatory Bowel Diseases/genetics ; Neural Networks, Computer ; }, abstract = {The human microbiome plays a crucial role in human health and is associated with a number of human diseases. Determining microbiome functional roles in human diseases remains a biological challenge due to the high dimensionality of metagenome gene features. However, existing models were limited in providing biological interpretability, where the functional role of microbes in human diseases is unexplored. Here we propose to utilize a neural network-based model incorporating Gene Ontology (GO) relationship network to discover the microbe functionality in human diseases. We use four benchmark datasets, including diabetes, liver cirrhosis, inflammatory bowel disease, and colorectal cancer, to explore the microbe functionality in the human diseases. Our model discovered and visualized the novel candidates' important microbiome genes and their functions by calculating the important score of each gene and GO term in the network. Furthermore, we demonstrate that our model achieves a competitive performance in predicting the disease by comparison with other non-Gene Ontology informed models. The discovered candidates' important microbiome genes and their functions provide novel insights into microbe functional contribution.}, }
@article {pmid37602324, year = {2023}, author = {Suryavanshi, M and Agudelo, J and Miller, A}, title = {Rare phylotypes in stone, stool, and urine microbiomes are associated with urinary stone disease.}, journal = {Frontiers in molecular biosciences}, volume = {10}, number = {}, pages = {1210225}, pmid = {37602324}, issn = {2296-889X}, abstract = {Introduction: In complex microbial communities, the importance of microbial species at very low abundance levels and their prevalence for overall community structure and function is increasingly being recognized. Clinical microbiome studies on urinary stone disease (USD) have indicated that both the gut and urinary tract microbiota are associated with the onset of the disease and that kidney stones them-selves harbor a complex, yet consistent and viable, microbiome. However, how rare phylotypes contribute to this association remains unclear. Delineating the contribution of rare and common phylotypes to urinary stone disease is important for the development of bacteriotherapies to promote urologic health. Methods: The objectives of the current report were to conduct a metaanalysis of 16S rRNA datasets derived from the kidney stone, stool, and urine samples of participants with or without urinary stone disease. To delineate the impact of rare and common phylotypes, metaanalyses were conducted by first separating rare and common taxa determined by both the frequency and abundance of amplicon sequence variants. Results: Consistent with previous analyses, we found that gut, upper urinary, and lower urinary tract microbiomes were all unique. Rare phylotypes comprised the majority of species observed in all sample types, with kidney stones exhibiting the greatest bias toward rarity, followed by urine and stool. Both rare and common fractions contributed significantly to the differences observed between sample types and health disparity. Furthermore, the rare and common fractions were taxonomically unique across all sample types. A total of 222 and 320 unique rare phylotypes from urine and stool samples were found to be significantly associated with USD. A co-occurrence correlation analysis revealed that rare phylotypes are most important for microbiome structure in stones, followed by urine and stool. Discussion: Collectively, the results indicate that rare phylotypes may be important for the pathophysiology of USD, particularly in the kidney stone matrix, which is inherently a very low microbial biomass niche that can have implications for the diagnosis and treatment of kidney stones. Further studies are needed to investigate the functional significance of rare phylotypes in kidney stone pathogenesis.}, }
@article {pmid37602232, year = {2023}, author = {Guo, C and Yi, B and Wu, J and Lu, J}, title = {The microbiome in post-acute infection syndrome (PAIS).}, journal = {Computational and structural biotechnology journal}, volume = {21}, number = {}, pages = {3904-3911}, pmid = {37602232}, issn = {2001-0370}, abstract = {Post-Acute Infection Syndrome (PAIS) is a relatively new medical terminology that represents prolonged sequelae symptoms after acute infection by numerous pathogenic agents. Imposing a substantial public health burden worldwide, PASC (post-acute sequelae of COVID-19 infection) and ME/CFS (myalgic encephalomyelitis/chronic fatigue syndrome) are two of the most recognized and prevalent PAIS conditions. The presences of prior infections and similar symptom profiles in PAIS reflect a plausible common etiopathogenesis. The human microbiome is known to play an essential role in health and disease. In this review, we reviewed and summarized available research on oral and gut microbiota alterations in patients with different infections or PAIS conditions. We discussed key theories about the associations between microbiome dysbiosis and PAIS disease development, aiming to explore the mechanistic roles and potential functions the microbiome may have in the process. Additionally, we discuss the areas of knowledge gaps and propose the potential clinical applications of the microbiome for prevention and treatment of PAIS conditions.}, }
@article {pmid37600938, year = {2023}, author = {Reuben, RC and Beugnon, R and Jurburg, SD}, title = {COVID-19 alters human microbiomes: a meta-analysis.}, journal = {Frontiers in cellular and infection microbiology}, volume = {13}, number = {}, pages = {1211348}, pmid = {37600938}, issn = {2235-2988}, mesh = {Humans ; *COVID-19 ; SARS-CoV-2 ; RNA, Ribosomal, 16S/genetics ; *Microbiota ; *Gastrointestinal Microbiome ; }, abstract = {INTRODUCTION: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has infected a substantial portion of the world's population, and novel consequences of COVID-19 on the human body are continuously being uncovered. The human microbiome plays an essential role in host health and well-being, and multiple studies targeting specific populations have reported altered microbiomes in patients infected with SARS-CoV-2. Given the global scale and massive incidence of COVID on the global population, determining whether the effects of COVID-19 on the human microbiome are consistent and generalizable across populations is essential.<br><br>METHODS: We performed a synthesis of human microbiome responses to COVID-19. We collected 16S rRNA gene amplicon sequence data from 11 studies sampling the oral and nasopharyngeal or gut microbiome of COVID-19-infected and uninfected subjects. Our synthesis included 1,159 respiratory (oral and nasopharyngeal) microbiome samples and 267 gut microbiome samples from patients in 11 cities across four countries.<br><br>RESULTS: Our reanalyses revealed communitywide alterations in the respiratory and gut microbiomes across human populations. We found significant overall reductions in the gut microbial diversity of COVID-19-infected patients, but not in the respiratory microbiome. Furthermore, we found more consistent community shifts in the gut microbiomes of infected patients than in the respiratory microbiomes, although the microbiomes in both sites exhibited higher host-to-host variation in infected patients. In respiratory microbiomes, COVID-19 infection resulted in an increase in the relative abundance of potentially pathogenic bacteria, including Mycoplasma.<br><br>DISCUSSION: Our findings shed light on the impact of COVID-19 on the human-associated microbiome across populations, and highlight the need for further research into the relationship between long-term effects of COVID-19 and altered microbiota.}, }
@article {pmid37596619, year = {2023}, author = {Li, F and Ling, X and Chakraborty, S and Fountzilas, C and Wang, J and Jamroze, A and Liu, X and Kalinski, P and Tang, DG}, title = {Role of the DEAD-box RNA helicase DDX5 (p68) in cancer DNA repair, immune suppression, cancer metabolic control, virus infection promotion, and human microbiome (microbiota) negative influence.}, journal = {Journal of experimental &amp; clinical cancer research : CR}, volume = {42}, number = {1}, pages = {213}, pmid = {37596619}, issn = {1756-9966}, support = {P30 CA016056/CA/NCI NIH HHS/United States ; R01 CA237027/CA/NCI NIH HHS/United States ; R44 CA176937/CA/NCI NIH HHS/United States ; 20-65-FENG/PCAN/Pancreatic Cancer Action Network/United States ; }, mesh = {Humans ; Male ; Cell Transformation, Neoplastic ; *DEAD-box RNA Helicases/genetics ; DNA Repair ; *Microbiota ; Prostatic Neoplasms ; Signal Transduction ; Immunosuppression Therapy ; }, abstract = {There is increasing evidence indicating the significant role of DDX5 (also called p68), acting as a master regulator and a potential biomarker and target, in tumorigenesis, proliferation, metastasis and treatment resistance for cancer therapy. However, DDX5 has also been reported to act as an oncosuppressor. These seemingly contradictory observations can be reconciled by DDX5's role in DNA repair. This is because cancer cell apoptosis and malignant transformation can represent the two possible outcomes of a single process regulated by DDX5, reflecting different intensity of DNA damage. Thus, targeting DDX5 could potentially shift cancer cells from a growth-arrested state (necessary for DNA repair) to apoptosis and cell killing. In addition to the increasingly recognized role of DDX5 in global genome stability surveillance and DNA damage repair, DDX5 has been implicated in multiple oncogenic signaling pathways. DDX5 appears to utilize distinct signaling cascades via interactions with unique proteins in different types of tissues/cells to elicit opposing roles (e.g., smooth muscle cells versus cancer cells). Such unique features make DDX5 an intriguing therapeutic target for the treatment of human cancers, with limited low toxicity to normal tissues. In this review, we discuss the multifaceted functions of DDX5 in DNA repair in cancer, immune suppression, oncogenic metabolic rewiring, virus infection promotion, and negative impact on the human microbiome (microbiota). We also provide new data showing that FL118, a molecular glue DDX5 degrader, selectively works against current treatment-resistant prostate cancer organoids/cells. Altogether, current studies demonstrate that DDX5 may represent a unique oncotarget for effectively conquering cancer with minimal toxicity to normal tissues.}, }
@article {pmid37592350, year = {2023}, author = {Zhou, J and Boyd, JA and Nyeverecz, B and Vivian, C and Angel, N and Wood, DLA and Hugenholtz, P and Tyson, GW and Krause, L and Ó Cuív, P}, title = {Draft genome sequence of two "Candidatus Intestinicoccus colisanans" strains isolated from faeces of healthy humans.}, journal = {BMC research notes}, volume = {16}, number = {1}, pages = {174}, pmid = {37592350}, issn = {1756-0500}, mesh = {Humans ; Feces ; *Gastrointestinal Microbiome/genetics ; Health Status ; Phylogeny ; Tissue Donors ; }, abstract = {OBJECTIVES: In order to provide a better insight into the functional capacity of the human gut microbiome, we isolated a novel bacterium, "Candidatus Intestinicoccus colisanans" gen. nov. sp. nov., and performed whole genome sequencing. This study will provide new insights into the functional potential of this bacterium and its role in modulating host health and well-being. We expect that this data resource will be useful in providing additional insight into the diversity and functional potential of the human microbiome.<br><br>DATA DESCRIPTION: Here, we report the first draft genome sequences of "Candidatus Intestinicoccus colisanans" strains MH27-1 and MH27-2, recovered from faeces collected from healthy human donors. The genomes were sequenced using short-read Illumina technology and whole-genome-based comparisons and phylogenomics reconstruction indicate that "Candidatus Intestinicoccus colisanans" represents a novel genus and species within the family Acutalibacteraceae. Both genomes were estimated to be >&#x2009;98% completed and to range in size from 2.9 to 3.3&#xa0;Mb with a G&#x2009;+&#x2009;C content of approximately 51%. The gene repertoire of "Candidatus Intestinicoccus colisanans" indicate it is likely a saccharolytic gut bacterium.}, }
@article {pmid37590208, year = {2023}, author = {Mallott, EK and Sitarik, AR and Leve, LD and Cioffi, C and Camargo, CA and Hasegawa, K and Bordenstein, SR}, title = {Human microbiome variation associated with race and ethnicity emerges as early as 3 months of age.}, journal = {PLoS biology}, volume = {21}, number = {8}, pages = {e3002230}, pmid = {37590208}, issn = {1545-7885}, support = {UH3 OD023389/OD/NIH HHS/United States ; P50 DA048756/DA/NIDA NIH HHS/United States ; R01 DA035062/DA/NIDA NIH HHS/United States ; UH3 OD023253/OD/NIH HHS/United States ; UG3 OD023253/OD/NIH HHS/United States ; }, mesh = {Adult ; Child ; Humans ; Ethnicity/genetics ; *Microbiota/genetics ; *Gastrointestinal Microbiome/genetics ; Knowledge ; Machine Learning ; }, abstract = {Human microbiome variation is linked to the incidence, prevalence, and mortality of many diseases and associates with race and ethnicity in the United States. However, the age at which microbiome variability emerges between these groups remains a central gap in knowledge. Here, we identify that gut microbiome variation associated with race and ethnicity arises after 3 months of age and persists through childhood. One-third of the bacterial taxa that vary across caregiver-identified racial categories in children are taxa reported to also vary between adults. Machine learning modeling of childhood microbiomes from 8 cohort studies (2,756 samples from 729 children) distinguishes racial and ethnic categories with 87% accuracy. Importantly, predictive genera are also among the top 30 most important taxa when childhood microbiomes are used to predict adult self-identified race and ethnicity. Our results highlight a critical developmental window at or shortly after 3 months of age when social and environmental factors drive race and ethnicity-associated microbiome variation and may contribute to adult health and health disparities.}, }
@article {pmid37587941, year = {2023}, author = {Dobon, B and Musciotto, F and Mira, A and Greenacre, M and Schlaepfer, R and Aguileta, G and Astete, LH and Ngales, M and Latora, V and Battiston, F and Vinicius, L and Migliano, AB and Bertranpetit, J}, title = {The making of the oral microbiome in Agta hunter-gatherers.}, journal = {Evolutionary human sciences}, volume = {5}, number = {}, pages = {e13}, pmid = {37587941}, issn = {2513-843X}, abstract = {Ecological and genetic factors have influenced the composition of the human microbiome during our evolutionary history. We analysed the oral microbiota of the Agta, a hunter-gatherer population where some members have adopted an agricultural diet. We show that age is the strongest factor modulating the microbiome, probably through immunosenescence since we identified an increase in the number of species classified as pathogens with age. We also characterised biological and cultural processes generating sexual dimorphism in the oral microbiome. A small subset of oral bacteria is influenced by the host genome, linking host collagen genes to bacterial biofilm formation. Our data also suggest that shifting from a fish/meat diet to a rice-rich diet transforms their microbiome, mirroring the Neolithic transition. All of these factors have implications in the epidemiology of oral diseases. Thus, the human oral microbiome is multifactorial and shaped by various ecological and social factors that modify the oral environment.}, }
@article {pmid37577371, year = {2023}, author = {Naud, S and Valles, C and Abdillah, A and Abou Chacra, L and Mekhalif, FZ and Ibrahim, A and Caputo, A and Baudoin, JP and Gouriet, F and Bittar, F and Lagier, JC and Ranque, S and Fenollar, F and Tidjani Alou, M and Raoult, D}, title = {Preliminary landscape of Candidatus Saccharibacteria in the human microbiome.}, journal = {Frontiers in cellular and infection microbiology}, volume = {13}, number = {}, pages = {1195679}, pmid = {37577371}, issn = {2235-2988}, mesh = {Female ; Humans ; Prospective Studies ; Retrospective Studies ; *Bacteria/genetics ; *Microbiota ; Real-Time Polymerase Chain Reaction ; }, abstract = {INTRODUCTION: Candidate Phyla Radiation (CPR) and more specifically Candidatus Saccharibacteria (TM7) have now been established as ubiquitous members of the human oral microbiota. Additionally, CPR have been reported in the gastrointestinal and urogenital tracts. However, the exploration of new human niches has been limited to date.<br><br>METHODS: In this study, we performed a prospective and retrospective screening of TM7 in human samples using standard PCR, real-time PCR, scanning electron microscopy (SEM) and shotgun metagenomics.<br><br>RESULTS: Using Real-time PCR and standard PCR, oral samples presented the highest TM7 prevalence followed by fecal samples, breast milk samples, vaginal samples and urine samples. Surprisingly, TM7 were also detected in infectious samples, namely cardiac valves and blood cultures at a low prevalence (under 3%). Moreover, we observed CPR-like structures using SEM in all sample types except cardiac valves. The reconstruction of TM7 genomes in oral and fecal samples from shotgun metagenomics reads further confirmed their high prevalence in some samples.<br><br>CONCLUSION: This study confirmed, through their detection in multiple human samples, that TM7 are human commensals that can also be found in clinical settings. Their detection in clinical samples warrants further studies to explore their role in a pathological setting.}, }
@article {pmid37574509, year = {2023}, author = {Kolsi, A and Haukka, K and Dougnon, V and Agbankpè, AJ and Fabiyi, K and Virta, M and Skurnik, M and Kantele, A and Kiljunen, S}, title = {Isolation and characterization of three novel Acinetobacter baumannii phages from Beninese hospital wastewater.}, journal = {Archives of virology}, volume = {168}, number = {9}, pages = {228}, pmid = {37574509}, issn = {1432-8798}, mesh = {Humans ; *Bacteriophages/genetics ; *Acinetobacter baumannii ; Wastewater ; Phylogeny ; Host Specificity ; Anti-Bacterial Agents ; }, abstract = {Acinetobacter baumannii is an opportunistic pathogen that is mostly associated with hospital-acquired infections. The rapid emergence of multi- and pan-drug-resistant Acinetobacter strains poses an increasing challenge in hospitals. Phage therapy offers one treatment option for infections caused by A. baumannii. We isolated three phages from Beninese hospital wastewater - fBenAci001, fBenAci002, and fBenAci003 - that infected clinical A. baumannii strains from Finnish patients. Phylogenetic analysis showed that these phages resemble phages of the genus Friunavirus, family Autographiviridae. The isolated phages meet the requirements set for phages used for phage therapy. However, they were found to have a narrow host range, which may limit their therapeutic use.}, }
@article {pmid37572831, year = {2023}, author = {Riekkinen, M and Pakkanen, SH and Hutse, V and Roukaerts, I and Ollgren, J and Käyhty, H and Herzog, C and Rombo, L and Kantele, A}, title = {Coadministered pneumococcal conjugate vaccine decreases immune response to hepatitis A vaccine: a randomized controlled trial.}, journal = {Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases}, volume = {29}, number = {12}, pages = {1553-1560}, doi = {10.1016/j.cmi.2023.08.006}, pmid = {37572831}, issn = {1469-0691}, mesh = {Humans ; Adolescent ; Adult ; Hepatitis A Vaccines/adverse effects ; Vaccines, Conjugate ; *Hepatitis A/prevention &amp; control ; Hepatitis A Antibodies ; Antibodies, Bacterial ; Pneumococcal Vaccines ; Streptococcus pneumoniae ; Immunity ; Immunoglobulin G ; *Pneumococcal Infections/prevention &amp; control ; Double-Blind Method ; }, abstract = {OBJECTIVES: We explored the influence of coadministration on safety and immunogenicity of the most common travellers' vaccine hepatitis A (HepA) and the pneumococcal conjugate vaccine (PCV) increasingly used both at home and before travel.<br><br>METHODS: Volunteers aged &#x2265;18&#xa0;years (n&#xa0;=&#xa0;305) were randomly assigned 1:1:1 into three groups receiving: 13-valent PCV (PCV13)&#xa0;+&#xa0;HepA, PCV13, or HepA. Anti-pneumococcal IgG concentrations, opsonophagocytic activity (OPA) titres, and total hepatitis A antibody (anti-HAV) concentrations were measured before and 28&#xa0;&#xb1;&#xa0;3&#xa0;days after vaccination. Adverse events (AEs) were recorded over 4&#xa0;weeks.<br><br>RESULTS: After vaccination, the anti-HAV geometric mean concentration was significantly lower in the PCV13+HepA than the HepA group: 34.47 mIU/mL (95% CI: 26.42-44.97 mIU/mL) versus 72.94 mIU/mL (95% CI: 55.01-96.72 mIU/mL), p&#xa0;<&#xa0;0.001. Anti-HAV &#x2265;10 mIU/mL considered protective was reached by 71 of 85 (83.5%) in the PCV13+HepA group versus 76 of 79 (96.2%) in the HepA group, p 0.008. The increases in anti-pneumococcal IgG and OPA levels were comparable in the PCV13+HepA and PCV13 groups, apart from a bigger rise in the PCV13+HepA group for serotype 3 (one-way ANOVA: serotype 3 IgG p 0.010, OPA p 0.002). AEs proved more frequent among those receiving PCV13 than HepA, but simultaneous administration did not increase the rates: &#x2265;one AE was reported by 45 of 56 (80.4%) PCV13, 43 of 54 (79.6%) PCV13+HepA, and 25 of 53 (47.2%) HepA recipients providing structured AE data.<br><br>DISCUSSION: Coadministration of HepA and PCV13 did not cause safety concerns, nor did it impact the patients' response to PCV13, apart from serotype 3. However, coadministered PCV13 significantly impaired antibody responses to HepA.}, }
@article {pmid37571295, year = {2023}, author = {Lupu, VV and Butnariu, LI and Fotea, S and Morariu, ID and Badescu, MC and Starcea, IM and Salaru, DL and Popp, A and Dragan, F and Lupu, A and Mocanu, A and Chisnoiu, T and Pantazi, AC and Jechel, E}, title = {The Disease with a Thousand Faces and the Human Microbiome-A Physiopathogenic Intercorrelation in Pediatric Practice.}, journal = {Nutrients}, volume = {15}, number = {15}, pages = {}, pmid = {37571295}, issn = {2072-6643}, mesh = {Humans ; Child ; *Gastrointestinal Microbiome ; Quality of Life ; *Microbiota ; *Lupus Erythematosus, Systemic/etiology ; Heart ; }, abstract = {Numerous interrelationships are known in the literature that have the final effect of unmasking or influencing various pathologies. Among these, the present article aims to discuss the connection between systemic lupus erythematosus (SLE) and the human microbiome. The main purpose of this work is to popularize information about the impact of dysbiosis on the pathogenesis and evolutionary course of pediatric patients with SLE. Added to this is the interest in knowledge and awareness of adjunctive therapeutic means that has the ultimate goal of increasing the quality of life. The means by which this can be achieved can be briefly divided into prophylactic or curative, depending on the phase of the condition in which the patient is. We thus reiterate the importance of the clinician acquiring an overview of SLE and the human microbiome, doubled by in-depth knowledge of the physio-pathogenic interactions between the two (in part achieved through the much-studied gut-target organ axes-brain, heart, lung, skin), with the target objective being that of obtaining individualized, multimodal and efficient management for each individual patient.}, }
@article {pmid37562360, year = {2023}, author = {Huang, Z and Zuo, T}, title = {The gut microbiome: Bridging medications and clinical outcomes post stem cell transplantation.}, journal = {Cell host &amp; microbe}, volume = {31}, number = {8}, pages = {1257-1259}, doi = {10.1016/j.chom.2023.06.012}, pmid = {37562360}, issn = {1934-6069}, mesh = {*Gastrointestinal Microbiome ; *Hematopoietic Stem Cell Transplantation ; }, abstract = {Anti-cancer therapies are usually intertwined with prolonged use of drugs, which may lead to different clinical outcomes. Recently in Cell and Cell Host &amp; Microbe, Nguyen et al. and Vallet et al., respectively, deconvolute the drug effects on gut microbiome dynamics underpinning clinical outcomes after allogeneic hematopoietic stem cell transplantation.}, }
@article {pmid37560521, year = {2023}, author = {Xiao, Y and Wu, K and Batool, SS and Wang, Q and Chen, H and Zhai, X and Yu, Z and Huang, J}, title = {Enzymatic properties of alcohol dehydrogenase PedE_M.s. derived from Methylopila sp. M107 and its broad metal selectivity.}, journal = {Frontiers in microbiology}, volume = {14}, number = {}, pages = {1191436}, pmid = {37560521}, issn = {1664-302X}, abstract = {As an important metabolic enzyme in methylotrophs, pyrroloquinoline quinone (PQQ)-dependent alcohol dehydrogenases play significant roles in the global carbon and nitrogen cycles. In this article, a calcium (Ca[2+])-dependent alcohol dehydrogenase PedE_M.s., derived from the methylotroph Methylopila sp. M107 was inserted into the modified vector pCM80 and heterologously expressed in the host Methylorubrum extorquens AM1. Based on sequence analysis, PedE_M.s., a PQQ-dependent dehydrogenase belonging to a methanol/ethanol family, was successfully extracted and purified. Showing by biochemical results, its enzymatic activity was detected as 0.72 U/mg while the Km value was 0.028 mM while employing ethanol as optimal substrate. The activity of PedE_M.s. could be enhanced by the presence of potassium (K[+]) and calcium (Ca[2+]), while acetonitrile and certain common detergents have been found to decrease the activity of PedE_M.s.. In addition, its optimum temperature and pH were 30°C and pH 9.0, respectively. Chiefly, as a type of Ca[2+]-dependent alcohol dehydrogenase, PedE_M.s. maintained 60-80% activity in the presence of 10 mM lanthanides and displayed high affinity for ethanol compared to other PedE-type enzymes. The 3D structure of PedE_M.s. was predicted by AlphaFold, and it had an 8-bladed propeller-like super-barrel. Meanwhile, we could speculate that PedE_M.s. contained the conserved residues Glu213, Asn300, and Asp350 through multiple sequence alignment by Clustal and ESpript. The analysis of enzymatic properties of PedE_M.s. enriches our knowledge of the methanol/ethanol family PQQ-dependent dehydrogenase. This study provides new ideas to broaden the application of alcohol dehydrogenase in alcohol concentration calculation, biosensor preparation, and other industries.}, }
@article {pmid37554313, year = {2023}, author = {Chowdhry, A and Kapoor, P and Bhargava, D and Bagga, DK}, title = {Exploring the oral microbiome: an updated multidisciplinary oral healthcare perspective.}, journal = {Discoveries (Craiova, Romania)}, volume = {11}, number = {2}, pages = {e165}, pmid = {37554313}, issn = {2359-7232}, abstract = {The oral cavity is home to diverse microbial content, collectively called as the oral microbiome. The latest technological advancements have unraveled the intricacies of the oral microbiome. It can be of great importance for oral health care givers to know the fundamentals and latest developments in the field of the oral microbiome, as oral dysbiosis is associated with many common diseases frequently seen and managed by them. These diseases include dental caries, periodontitis, mucosal diseases (such as oral leukoplakia, oral lichen planus, and systemic lupus erythematosus), oral cancers, and even co-infections related to the current COVID-19 pandemic. The emergence of new genomic and molecular biology methodologies has been pivotal for understanding the role of the human microbiome in health and disease. The current review compiles oral microbiome in health and disease with a multidisciplinary dental approach. The insight into the oral microbiome, which is provided dental specialty wise in the current article will initiate and guide researchers of various disciplines in developing microbiome-based therapeutic or prophylactic management strategies, managing public health challenges by microbiome-based boarder interventions and divert resources for preserving and achieving a balanced oral microbiome.}, }
@article {pmid37552810, year = {2023}, author = {Bahuguna, A and Dubey, SK}, title = {Overview of the Mechanistic Potential of Probiotics and Prebiotics in Cancer Chemoprevention.}, journal = {Molecular nutrition &amp; food research}, volume = {67}, number = {19}, pages = {e2300221}, doi = {10.1002/mnfr.202300221}, pmid = {37552810}, issn = {1613-4133}, abstract = {Despite of strides in modern cancer therapeutic strategies, there has not been a successful cure for it until now and prognostic side effects and substantial toxicity to chemotherapy and subsequent homeostatic imbalance remains a major concern for professionals in this field. The significance of the human microbiome in the pathogenesis of cancer is being recognized, documented, and established worldwide. Probiotics and prebiotics are some of the most extensively researched approaches to modulate the microbiota for therapeutic purposes, and research on their potential to prevent and treat cancer has sparked an immense amount of interest. The characteristics of probiotics and prebiotics allow for an array of efficient applications in cancer preventive measures. Probiotics can also be administered coupled with chemotherapy and surgery to alleviate their side effects and help promote the effectiveness of chemotherapeutic drugs. Besides showing promising results they are accompanied by potential risks and controversies that may eventually result in clinical repercussions. This review emphasizes the mechanistic potential and oncosuppressive effects of probiotic and prebiotics through maintenance of intestinal barrier function, modifying innate immune system, immunomodulation, intestinal microbiota metabolism, inhibition of host cell proliferation, preventing pathogen colonization, and exerting selective cytotoxicity against tumor cells.}, }
@article {pmid37548476, year = {2023}, author = {Bucci, V and Ward, DV and Bhattarai, S and Rojas-Correa, M and Purkayastha, A and Holler, D and Qu, MD and Mitchell, WG and Yang, J and Fountain, S and Zeamer, A and Forconi, CS and Fujimori, G and Odwar, B and Cawley, C and Moormann, AM and Wessolossky, M and Maldonado-Contreras, A}, title = {The intestinal microbiota predicts COVID-19 severity and fatality regardless of hospital feeding method.}, journal = {mSystems}, volume = {8}, number = {4}, pages = {e0031023}, pmid = {37548476}, issn = {2379-5077}, support = {U01 CA261276/CA/NCI NIH HHS/United States ; }, mesh = {Humans ; *Gastrointestinal Microbiome ; *COVID-19 ; SARS-CoV-2 ; Feeding Methods ; Hospitals ; }, abstract = {SARS-CoV-2-positive patients exhibit gut and oral microbiome dysbiosis, which is associated with various aspects of COVID-19 disease (1-4). Here, we aim to identify gut and oral microbiome markers that predict COVID-19 severity in hospitalized patients, specifically severely ill patients compared to moderately ill ones. Moreover, we investigate whether hospital feeding (solid versus enteral), an important cofounder, influences the microbial composition of hospitalized COVID-19 patients. We used random forest classification machine learning models with interpretable secondary analyses. The gut, but not the oral microbiota, was a robust predictor of both COVID-19-related fatality and severity of hospitalized patients, with a higher predictive value than most clinical variables. In addition, perturbations of the gut microbiota due to enteral feeding did not associate with species that were predictive of COVID-19 severity. IMPORTANCE SARS-CoV-2 infection leads to wide-ranging, systemic symptoms with sometimes unpredictable morbidity and mortality. It is increasingly clear that the human microbiome plays an important role in how individuals respond to viral infections. Our study adds to important literature about the associations of gut microbiota and severe COVID-19 illness during the early phase of the pandemic before the availability of vaccines. Increased understanding of the interplay between microbiota and SARS-CoV-2 may lead to innovations in diagnostics, therapies, and clinical predictions.}, }
@article {pmid37545638, year = {2023}, author = {Maslennikov, R and Alieva, A and Poluektova, E and Zharikov, Y and Suslov, A and Letyagina, Y and Vasileva, E and Levshina, A and Kozlov, E and Ivashkin, V}, title = {Sarcopenia in cirrhosis: Prospects for therapy targeted to gut microbiota.}, journal = {World journal of gastroenterology}, volume = {29}, number = {27}, pages = {4236-4251}, pmid = {37545638}, issn = {2219-2840}, mesh = {Animals ; *Gastrointestinal Microbiome/physiology ; Dysbiosis/microbiology ; *Sarcopenia/etiology/therapy ; Liver Cirrhosis/complications/therapy/microbiology ; }, abstract = {Decreased muscle mass and function, also known as sarcopenia, is common in patients with cirrhosis and is associated with a poor prognosis. Although the pathogenesis of this disorder has not been fully elucidated, a disordered gut-muscle axis probably plays an important role. Decreased barrier function of the gut and liver, gut dysbiosis, and small intestinal bacterial overgrowth (SIBO) can lead to increased blood levels of ammonia, lipopolysaccharides, pro-inflammatory mediators, and myostatin. These factors have complex negative effects on muscle mass and function. Drug interventions that target the gut microbiota (long-term use of rifaximin, lactulose, lactitol, or probiotics) positively affect most links of the compromised gut-muscle axis in patients with cirrhosis by decreasing the levels of hyperammonemia, bacterial translocation, and systemic inflammation and correcting gut dysbiosis and SIBO. However, although these drugs are promising, they have not yet been investigated in randomized controlled trials specifically for the treatment and prevention of sarcopenia in patients with cirrhosis. No data exist on the effects of fecal transplantation on most links of gut-muscle axis in cirrhosis; however, the results of animal experimental studies are promising.}, }
@article {pmid37539732, year = {2023}, author = {Jotshi, A and Sukla, KK and Haque, MM and Bose, C and Varma, B and Koppiker, CB and Joshi, S and Mishra, R}, title = {Exploring the human microbiome - A step forward for precision medicine in breast cancer.}, journal = {Cancer reports (Hoboken, N.J.)}, volume = {6}, number = {11}, pages = {e1877}, pmid = {37539732}, issn = {2573-8348}, mesh = {Female ; Humans ; *Breast Neoplasms/genetics/therapy ; Precision Medicine ; Dysbiosis ; Artificial Intelligence ; *Microbiota/genetics ; }, abstract = {BACKGROUND: The second most frequent cancer in the world and the most common malignancy in women is breast cancer. Breast cancer is a significant health concern in India with a high mortality-to-incidence ratio and presentation at a younger age.<br><br>RECENT FINDINGS: Recent studies have identified gut microbiota as a significant factor that can have an influence on the development, treatment, and prognosis of breast cancer. This review article aims to describe the influence of microbial dysbiosis on breast cancer occurrence and the possible interactions between oncobiome and specific breast cancer molecular subtypes. The review further also discusses the role of epigenetics and diet/nutrition in the regulation of the gut and breast microbiome and its association with breast cancer prevention, therapy, and recurrence. Additionally, the recent technological advances in microbiome research, including next-generation sequencing (NGS) technologies, genome sequencing, single-cell sequencing, and microbial metabolomics along with recent advances in artificial intelligence (AI) have also been reviewed. This is an attempt to present a comprehensive status of the microbiome as a key cancer biomarker.<br><br>CONCLUSION: We believe that correlating microbiome and carcinogenesis is important as it can provide insights into the mechanisms by which microbial dysbiosis can influence cancer development and progression, leading to the potential use of the microbiome as a tool for prognostication and personalized therapy.}, }
@article {pmid37533117, year = {2023}, author = {Pantoja-Feliciano De Goodfellow, IG and Agans, R and Barbato, R and Colston, S and Goodson, MS and Hammamieh, R and Hentchel, K and Jones, R and Karl, JP and Kokoska, R and Leary, DH and Mauzy, C and Racicot, K and Stamps, BW and Varaljay, V and Soares, JW}, title = {Meeting report of the sixth annual tri-service microbiome consortium symposium.}, journal = {Environmental microbiome}, volume = {18}, number = {1}, pages = {66}, pmid = {37533117}, issn = {2524-6372}, abstract = {The Tri-Service Microbiome Consortium (TSMC) was founded to enhance collaboration, coordination, and communication of microbiome research among DoD organizations and to facilitate resource, material and information sharing amongst consortium members, which includes collaborators in academia and industry. The 6th Annual TSMC Symposium was a hybrid meeting held in Fairlee, Vermont on 27-28 September 2022 with presentations and discussions centered on microbiome-related topics within seven broad thematic areas: (1) Human Microbiomes: Stress Response; (2) Microbiome Analysis &amp; Surveillance; (3) Human Microbiomes Enablers &amp; Engineering; (4) Human Microbiomes: Countermeasures; (5) Human Microbiomes Discovery - Earth &amp; Space; (6) Environmental Micro &amp; Myco-biome; and (7) Environmental Microbiome Analysis &amp; Engineering. Collectively, the symposium provided an update on the scope of current DoD microbiome research efforts, highlighted innovative research being done in academia and industry that can be leveraged by the DoD, and fostered collaborative opportunities. This report summarizes the activities and outcomes from the 6th annual TSMC symposium.}, }
@article {pmid37532819, year = {2023}, author = {Fletcher, AA and Kelly, MS and Eckhoff, AM and Allen, PJ}, title = {Revisiting the intrinsic mycobiome in pancreatic cancer.}, journal = {Nature}, volume = {620}, number = {7972}, pages = {E1-E6}, pmid = {37532819}, issn = {1476-4687}, support = {K23 AI135090/AI/NIAID NIH HHS/United States ; T32 CA093245/CA/NCI NIH HHS/United States ; }, mesh = {Humans ; *Mycobiome ; *Pancreatic Neoplasms/genetics ; Pancreas ; Carcinogenesis ; }, abstract = {A growing body of literature suggests that alterations in the human microbiome are causative of disease initiation and progression. Aykut et al. present data supporting the argument that alterations in the gut fungal microbiome (the “mycobiome”), along with the presence of fungal elements within pancreatic tissue (specifically those of the genus Malassezia), are associated with pancreatic oncogenesis. Upon analyzing the human sequencing data presented in the original manuscript, we found few fungal reads in pancreatic tissue samples and did not identify differences in pancreatic or gut mycobiome composition between healthy and pancreatic ductal adenocarcinoma (PDAC) patients. Our re-analysis of these data does not support an association between an intrinsic pancreatic mycobiome and the development of human PDAC, and illustrates the challenges in analyzing microbiome sequencing data from low biomass samples.}, }
@article {pmid37528343, year = {2023}, author = {Chopyk, J and Cobián Güemes, AG and Ramirez-Sanchez, C and Attai, H and Ly, M and Jones, MB and Liu, R and Liu, C and Yang, K and Tu, XM and Abeles, SR and Nelson, K and Pride, DT}, title = {Common antibiotics, azithromycin and amoxicillin, affect gut metagenomics within a household.}, journal = {BMC microbiology}, volume = {23}, number = {1}, pages = {206}, pmid = {37528343}, issn = {1471-2180}, support = {T32 AI007036/AI/NIAID NIH HHS/United States ; }, mesh = {Humans ; *Anti-Bacterial Agents/pharmacology ; *Amoxicillin/pharmacology ; Azithromycin/pharmacology ; Metagenomics ; Macrolides/pharmacology ; Drug Resistance, Bacterial ; }, abstract = {BACKGROUND: The microbiome of the human gut serves a role in a number of physiological processes, but can be altered through effects of age, diet, and disturbances such as antibiotics. Several studies have demonstrated that commonly used antibiotics can have sustained impacts on the diversity and the composition of the gut microbiome. The impact of the two most overused antibiotics, azithromycin, and amoxicillin, in the human microbiome has not been thoroughly described. In this study, we recruited a group of individuals and unrelated controls to decipher the effects of the commonly used antibiotics amoxicillin and azithromycin on their gut microbiomes.<br><br>RESULTS: We characterized the gut microbiomes by metagenomic sequencing followed by characterization of the resulting microbial communities. We found that there were clear and sustained effects of the antibiotics on the gut microbial community with significant alterations in the representations of Bifidobacterium species in response to azithromycin (macrolide antibiotic). These results were supported by significant increases identified in putative antibiotic resistance genes associated with macrolide resistance. Importantly, we did not identify these trends in the unrelated control individuals. There were no significant changes observed in other members of the microbial community.<br><br>CONCLUSIONS: As we continue to focus on the role that the gut microbiome plays and how disturbances induced by antibiotics might affect our overall health, elucidating members of the community most affected by their use is of critical importance to understanding the impacts of common antibiotics on those who take them. Clinical Trial Registration Number NCT05169255. This trial was retrospectively registered on 23-12-2021.}, }
@article {pmid37527009, year = {2023}, author = {Yang, C and Mai, J and Cao, X and Burberry, A and Cominelli, F and Zhang, L}, title = {ggpicrust2: an R package for PICRUSt2 predicted functional profile analysis and visualization.}, journal = {Bioinformatics (Oxford, England)}, volume = {39}, number = {8}, pages = {}, pmid = {37527009}, issn = {1367-4811}, support = {P30 DK097948/DK/NIDDK NIH HHS/United States ; R01 DK042191/DK/NIDDK NIH HHS/United States ; P30 AG072959/AG/NIA NIH HHS/United States ; }, mesh = {Humans ; Software ; RNA, Ribosomal, 16S/genetics ; Phylogeny ; *Microbiota ; *Gastrointestinal Microbiome ; }, abstract = {SUMMARY: Microbiome research is now moving beyond the compositional analysis of microbial taxa in a sample. Increasing evidence from large human microbiome studies suggests that functional consequences of changes in the intestinal microbiome may provide more power for studying their impact on inflammation and immune responses. Although 16S rRNA analysis is one of the most popular and a cost-effective method to profile the microbial compositions, marker-gene sequencing cannot provide direct information about the functional genes that are present in the genomes of community members. Bioinformatic tools have been developed to predict microbiome function with 16S rRNA gene data. Among them, PICRUSt2 (Phylogenetic Investigation of Communities by Reconstruction of Unobserved States) has become one of the most popular functional profile prediction tools, which generates community-wide pathway abundances. However, no state-of-art inference tools are available to test the differences in pathway abundances between comparison groups. We have developed ggpicrust2, an R package, for analyzing functional profiles derived from 16S rRNA sequencing. This powerful tool enables researchers to conduct extensive differential abundance analyses and generate visually appealing visualizations that effectively highlight functional signals. With ggpicrust2, users can obtain publishable results and gain deeper insights into the functional composition of their microbial communities.<br><br>The package is open-source under the MIT and file license and is available at CRAN and https://github.com/cafferychen777/ggpicrust2. Its shiny web is available at https://a95dps-caffery-chen.shinyapps.io/ggpicrust2_shiny/.}, }
@article {pmid37524974, year = {2023}, author = {Walker, AW and Hoyles, L}, title = {Human microbiome myths and misconceptions.}, journal = {Nature microbiology}, volume = {8}, number = {8}, pages = {1392-1396}, pmid = {37524974}, issn = {2058-5276}, mesh = {Humans ; *Communication ; }, abstract = {Over the past two decades, interest in human microbiome research has increased exponentially. Regrettably, this increased activity has brought with it a degree of hype and misinformation, which can undermine progress and public confidence in the research. Here we highlight selected human microbiome myths and misconceptions that lack a solid evidence base. By presenting these examples, we hope to draw increased attention to the implications of inaccurate dogma becoming embedded in the literature, and the importance of acknowledging nuance when describing the complex human microbiome.}, }
@article {pmid37524139, year = {2023}, author = {Lane, JM and Wright, RO and Eggers, S}, title = {The interconnection between obesity and executive function in adolescence: The role of the gut microbiome.}, journal = {Neuroscience and biobehavioral reviews}, volume = {153}, number = {}, pages = {105337}, pmid = {37524139}, issn = {1873-7528}, support = {R00 ES032884/ES/NIEHS NIH HHS/United States ; K99 ES032884/ES/NIEHS NIH HHS/United States ; R01 ES013744/ES/NIEHS NIH HHS/United States ; T32 HD049311/HD/NICHD NIH HHS/United States ; UL1 TR004419/TR/NCATS NIH HHS/United States ; }, mesh = {Adolescent ; Humans ; *Gastrointestinal Microbiome/physiology ; Executive Function ; *Pediatric Obesity/complications ; *Microbiota ; Brain/metabolism ; }, abstract = {In the United States, adolescent obesity is a growing epidemic associated with maladaptive executive functioning. Likewise, data link the microbiome to obesity. Emerging microbiome research has demonstrated an interconnection between the gut microbiome and the brain, indicating a bidirectional communication system within the gut-microbiome-brain axis in the pathophysiology of obesity. This narrative review identifies and summarizes relevant research connecting adolescent obesity as it relates to three core domains of executive functioning and the contribution of the gut microbiome in the relationship between obesity and executive functions in adolescence. The review suggests that (1) the interconnection between obesity, executive function, and the gut microbiome is a bidirectional connection, and (2) the gut microbiome may mediate the neurobiological pathways between obesity and executive function deficits. The findings of this review provide valuable insights into obesity-associated executive function deficits and elucidate the possible mediation role of the gut microbiome.}, }
@article {pmid37523293, year = {2023}, author = {Maigoro, AY and Muhammad, M and Bello, B and Useh, U and Lee, S}, title = {Exploration of Gut Microbiome Research in Africa: A Scoping Review.}, journal = {Journal of medicinal food}, volume = {26}, number = {9}, pages = {616-623}, doi = {10.1089/jmf.2023.K.0005}, pmid = {37523293}, issn = {1557-7600}, mesh = {Humans ; *Gastrointestinal Microbiome ; *Microbiota ; Africa ; Dietary Supplements ; }, abstract = {The crucial role of the gut microbiome in various diseases has led to increased interest in interventions and therapeutics targeting the human microbiome. Accordingly, the current scoping review analyzed the diseases and interventions involved in gut microbiome research in Africa. The electronic databases of PubMed, Google Scholar, and Scopus were searched from inception to October 2021. This study identified 48 studies involving 7073 study participants. Of the 48 studies, 20 (42%) used interventions to modulate gut microbiota, whereas the remaining 28 (58%) did not. Out of the total African countries, only 13% were involved in intervention-based gut microbiome research, whereas a larger proportion of 67% were not involved in any gut microbiome research. The interventions used in gut microbiome research in Africa include supplements, natural products, educational approaches, associated pathogens, albendazole, fresh daily yogurt, iron-containing lipid-based nutrient supplements, fecal microbiota transplant, and prophylactic cotrimoxazole. This scoping review highlights the current state of gut microbiome research in Africa. The findings of this review can inform the design of future studies and interventions aimed at improving gut health in African populations.}, }
@article {pmid37516837, year = {2023}, author = {Salonen, T and Jokinen, E and Satokari, R and Lahtinen, P}, title = {Randomized, double-blinded, placebo-controlled pilot study: efficacy of faecal microbiota transplantation on chronic fatigue syndrome.}, journal = {Journal of translational medicine}, volume = {21}, number = {1}, pages = {513}, pmid = {37516837}, issn = {1479-5876}, mesh = {Humans ; Female ; Male ; Adult ; *Fatigue Syndrome, Chronic/therapy ; Fecal Microbiota Transplantation ; Pilot Projects ; Quality of Life ; Double-Blind Method ; }, abstract = {BACKGROUND: Chronic fatigue syndrome (CFS) is a disabling illness of unknown aetiology. Disruption of gut microbiota may play a role in several neurological disorders. In this study, the effect of faecal microbiota transplantation (FMT) on fatigue severity and health-related quality of life (HRQOL) in patients with CFS was evaluated.<br><br>METHODS: Randomized, placebo-controlled pilot trial. Patients and researchers were blinded to treatment assignment. 11 patients with CFS (10 female and 1 male, mean age 42.2&#xa0;years and mean duration of CFS 6.3&#xa0;years) were randomly assigned to receive either FMT from a universal donor (n&#x2009;=&#x2009;5) or autologous FMT (n&#x2009;=&#x2009;6) via colonoscopy. Patients' HRQOL was assessed by using visual analog scale (VAS) and self-reporting questionnaires Modified Fatigue Impact Scale (MFIS), 15D and EQ-5D-3L. Patients' HRQOL was evaluated at baseline, and 1 and 6&#xa0;months after the FMT.<br><br>RESULTS: The baseline VAS scores in the FMT and placebo groups were 62.4 and 76.0 (p&#x2009;=&#x2009;0.29). 1-month scores were 60.0 and 73.7 and 6-months scores 72.8 and 69.5, respectively. Total MFIS scores in the FMT and placebo groups were 59.6 and 61.0 at the baseline (p&#x2009;=&#x2009;0.80), 53.5 and 62.0 at 1&#xa0;month and 58.6 and 56.2 at 6&#xa0;months. Compared to the baseline scores, differences at 1 and 6&#xa0;months were statistically insignificant both in VAS and in MFIS. The 15D and EQ-5D-3L profiles did not change after the FMT or placebo. FMT-related adverse events were not reported.<br><br>CONCLUSION: FMT was safe but did not relieve symptoms or improve the HRQOL of patients with CFS. Small number of study subjects limits the generalizability of these results. Trial Registration ClinicalTrials.gov Identifier NCT04158427, https://register.<br><br>CLINICALTRIALS: gov , date of registration 08/08/2019.}, }
@article {pmid37513952, year = {2023}, author = {Aslan, I and Tarhan Celebi, L and Kayhan, H and Kizilay, E and Gulbahar, MY and Kurt, H and Cakici, B}, title = {Probiotic Formulations Containing Fixed and Essential Oils Ameliorates SIBO-Induced Gut Dysbiosis in Rats.}, journal = {Pharmaceuticals (Basel, Switzerland)}, volume = {16}, number = {7}, pages = {}, pmid = {37513952}, issn = {1424-8247}, abstract = {Dysbiosis of the gut microbiota is associated with the pathogenesis of intestinal diseases such as inflammatory bowel disease, irritable bowel syndrome (IBS), small intestinal bacterial overgrowth (SIBO), and metabolic disease states such as allergies, cardiovascular diseases, obesity, and diabetes. SIBO is a condition characterized by an increased number (>1 × 10[3] CFU) of abnormal bacterial species in the small intestine. Interest in SIBO has gained importance due to increased awareness of the human microbiome and its potential relationships with human health and disease, which has encouraged new work in this area. In recent years, standard antibiotic regimens (rifaximin and metronidazole) have been used to treat SIBO, but solo antibiotics or their derivatives are insufficient. In this study, the therapeutic effects of the probiotic form, which contains coconut oil and traces of peppermint-lemon-patchouli essential oil, were evaluated on the Dysbiosis-Based Rat SIBO Model. There are significant differences between sick and healthy rats (p = 0.014), between sick rats and rats treated with the oil mix plus probiotic mix protocol (p = 0.026), and between rats treated with only the probiotic and only oil protocols (p = 0.030) in the evaluation of TNF-α levels. Histologically, villi distortion and loss of crypts, epithelial shedding and necrotic changes in the apical regions of the villi, and inflammatory cell infiltrations extending to the lamina propria and submucosa were observed in sick rats. Mitotic figures in villus epithelium and crypts were observed in rats treated with 9.2 × 10[9] CFU/1000 mg/coconut oil + trace amounts of peppermint-lemon-patchouli essential oil and a probiotic mixture (oil + probiotic mix protocol). A regression of inflammatory reactions and an increase in goblet cells were observed. A decrease was observed in inflammation markers in sick rats. On the other hand, the oil plus probiotic mix protocol recovered digestive system defects in the animals caused by dysbiosis. In the future, these treatment approaches can be effective in the treatment of SIBO.}, }
@article {pmid37512565, year = {2023}, author = {Cao, X and Zolnikova, O and Maslennikov, R and Reshetova, M and Poluektova, E and Bogacheva, A and Zharkova, M and Ivashkin, V}, title = {Differences in Fecal Short-Chain Fatty Acids between Alcoholic Fatty Liver-Induced Cirrhosis and Non-alcoholic (Metabolic-Associated) Fatty Liver-Induced Cirrhosis.}, journal = {Metabolites}, volume = {13}, number = {7}, pages = {}, pmid = {37512565}, issn = {2218-1989}, abstract = {The objective of this study was to investigate the metabolic activity of the gut microbiota in cirrhosis due to different variants of fatty liver disease (alcoholic vs. non-alcoholic [metabolic-associated] one [AFLD and MAFLD]). The present study included 24 patients with alcoholic liver cirrhosis, 16 patients with MAFLD-related cirrhosis, and 20 healthy controls. The level and spectrum of short-chain fatty acids (SCFAs) were determined via gas-liquid chromatography. All patients with cirrhosis showed a decrease in the total content of SCFAs (p < 0.001) and absolute content of acetate (p < 0.001), propionate (p < 0.001), butyrate (p < 0.001), and isovalerate (p < 0.001). In MAFLD cirrhosis, the metabolic activity of the microbiota was significantly altered compared to patients with alcoholic cirrhosis, as evidenced by a lower total SCFA content (p < 0.001) and absolute content of acetate (p < 0.001), propionate (p < 0.001), and butyrate (p < 0.001); a higher relative content of isovalerate (p < 0.001); and a higher IsoCn/Cn ratio (p < 0.001). Various clinical and laboratory parameters correlate differently with fecal SCFAs and their fractions in cirrhosis due to AFLD and MAFLD. SCFA-producing metabolic activity is reduced more in MAFLD cirrhosis than in alcoholic cirrhosis. According to the etiological factors of cirrhosis, disorders of this metabolic activity may be involved in different pathogenetic pathways.}, }
@article {pmid37511612, year = {2023}, author = {Mendes, I and Vale, N}, title = {How Can the Microbiome Induce Carcinogenesis and Modulate Drug Resistance in Cancer Therapy?.}, journal = {International journal of molecular sciences}, volume = {24}, number = {14}, pages = {}, pmid = {37511612}, issn = {1422-0067}, mesh = {Humans ; *Gastrointestinal Microbiome ; Carcinogenesis ; *Microbiota/genetics ; *Neoplasms/drug therapy/genetics ; Drug Resistance ; }, abstract = {Over the years, cancer has been affecting the lives of many people globally and it has become one of the most studied diseases. Despite the efforts to understand the cell mechanisms behind this complex disease, not every patient seems to respond to targeted therapies or immunotherapies. Drug resistance in cancer is one of the limiting factors contributing to unsuccessful therapies; therefore, understanding how cancer cells acquire this resistance is essential to help cure individuals affected by cancer. Recently, the altered microbiome was observed to be an important hallmark of cancer and therefore it represents a promising topic of cancer research. Our review aims to provide a global perspective of some cancer hallmarks, for instance how genetic and epigenetic modifications may be caused by an altered human microbiome. We also provide information on how an altered human microbiome can lead to cancer development as well as how the microbiome can influence drug resistance and ultimately targeted therapies. This may be useful to develop alternatives for cancer treatment, i.e., future personalized medicine that can help in cases where traditional cancer treatment is unsuccessful.}, }
@article {pmid37511022, year = {2023}, author = {Neidhöfer, C and Bagniceva, M and Wetzig, N and Sieber, MA and Thiele, R and Parčina, M}, title = {Pragmatic Considerations When Extracting DNA for Metagenomics Analyses of Clinical Samples.}, journal = {International journal of molecular sciences}, volume = {24}, number = {14}, pages = {}, pmid = {37511022}, issn = {1422-0067}, mesh = {DNA, Bacterial/genetics ; *Metagenomics/methods ; Sequence Analysis, DNA/methods ; RNA, Ribosomal, 16S/genetics ; *DNA ; }, abstract = {Microbiome analyses are essential for understanding microorganism composition and diversity, but interpretation is often challenging due to biological and technical variables. DNA extraction is a critical step that can significantly bias results, particularly in samples containing a high abundance of challenging-to-lyse microorganisms. Taking into consideration the distinctive microenvironments observed in different bodily locations, our study sought to assess the extent of bias introduced by suboptimal bead-beating during DNA extraction across diverse clinical sample types. The question was whether complex targeted extraction methods are always necessary for reliable taxonomic abundance estimation through amplicon sequencing or if simpler alternatives are effective for some sample types. Hence, for four different clinical sample types (stool, cervical swab, skin swab, and hospital surface swab samples), we compared the results achieved from extracting targeted manual protocols routinely used in our research lab for each sample type with automated protocols specifically not designed for that purpose. Unsurprisingly, we found that for the stool samples, manual extraction protocols with vigorous bead-beating were necessary in order to avoid erroneous taxa proportions on all investigated taxonomic levels and, in particular, false under- or overrepresentation of important genera such as Blautia, Faecalibacterium, and Parabacteroides. However, interestingly, we found that the skin and cervical swab samples had similar results with all tested protocols. Our results suggest that the level of practical automation largely depends on the expected microenvironment, with skin and cervical swabs being much easier to process than stool samples. Prudent consideration is necessary when extending the conclusions of this study to applications beyond rough estimations of taxonomic abundance.}, }
@article {pmid37509225, year = {2023}, author = {Pandey, A and Lieu, CH and Kim, SS}, title = {The Local Microbiome in Esophageal Cancer and Treatment Response: A Review of Emerging Data and Future Directions.}, journal = {Cancers}, volume = {15}, number = {14}, pages = {}, pmid = {37509225}, issn = {2072-6694}, abstract = {UNLABELLED: The incidence of esophageal cancer is increasing worldwide, with established risk factors explaining only a small fraction of cases. Currently, there are no established screening protocols in most countries, and treatment options are limited. The human microbiome has been implicated in carcinogenesis and the cancer treatment response. The advent of nucleic acid sequencing technologies has enabled more comprehensive, culture-independent bacterial identification. Across several tumor types, studies of tissue-specific microbiomes have shown associations between the overall microbiome composition, the relative abundance of specific bacteria, and tumorigenesis. Furthermore, in the era of cancer immunotherapy, several studies have demonstrated that the microbiome and specific bacteria may modify treatment responses and the risk of immune-related adverse events.<br><br>DESIGN: peer-reviewed, published studies describing the role of local, gastrointestinal-specific microbiota or the role of the gut microbiome in treatment responses were reviewed. PubMed was searched from 1 September 2022 to 1 November 2022, using the following terms in combination: "microbiome", "tumor microbiome", "esophageal cancer", "cancer", "cancer treatment", and "immunotherapy". Original research articles were considered, and other reviews or editorials were discarded. In total, approximately 250 articles were considered.<br><br>RESULTS: over 70 studies describing microbiome research in either gastrointestinal carcinogenesis or the systemic treatment response were identified and reviewed.<br><br>CONCLUSIONS: a growing body of evidence supports the role of the esophageal microbiome in both esophageal tumorigenesis and the immune checkpoint inhibitor response. More well-designed, comprehensive studies are required to collect the appropriate clinical, microbial, and immunophenotype data that are needed to clarify the precise role of the microbiome in esophageal carcinogenesis and treatment.}, }
@article {pmid37508310, year = {2023}, author = {Nyhamar, E and Webber, P and Liong, O and Yilmaz, &#xd6; and Pajunen, M and Skurnik, M and Wan, X}, title = {Discovery of Bactericidal Proteins from Staphylococcus Phage Stab21 Using a High-Throughput Screening Method.}, journal = {Antibiotics (Basel, Switzerland)}, volume = {12}, number = {7}, pages = {}, pmid = {37508310}, issn = {2079-6382}, support = {288701//Academy of Finland/ ; 200050//Jane and Aatos Erkko Foundation/ ; Decision 2016//Jane and Aatos Erkko Foundation/ ; }, abstract = {In the escalating battle against antimicrobial resistance, there is an urgent need to discover and investigate new antibiotic strategies. Bacteriophages are untapped reservoirs of such potential antimicrobials. This study focused on Hypothetical Proteins of Unknown Function (HPUFs) from a Staphylococcus phage Stab21. We examined its HPUFs for bactericidal activity against E. coli using a Next Generation Sequencing (NGS)-based approach. Among the 96 HPUFs examined, 5 demonstrated cross-species toxicity towards E. coli, suggesting the presence of shared molecular targets between E. coli and S. aureus. One toxic antibacterial HPUF (toxHPUF) was found to share homology with a homing endonuclease. The implications of these findings are profound, particularly given the potential broad applicability of these bactericidal agents. This study confirms the efficacy of NGS in streamlining the screening process of toxHPUFs, contributes significantly to the ongoing exploration of phage biology, and offers promises in the search for potent antimicrobial agents.}, }
@article {pmid37501991, year = {2023}, author = {Abot, A and Brochot, A and Pomié, N and Astre, G and Druart, C and de Vos, WM and Knauf, C and Cani, PD}, title = {Pasteurized Akkermansia muciniphila improves glucose metabolism is linked with increased hypothalamic nitric oxide release.}, journal = {Heliyon}, volume = {9}, number = {7}, pages = {e18196}, pmid = {37501991}, issn = {2405-8440}, abstract = {BACKGROUND AND OBJECTIVE: Pasteurized Akkermansia muciniphila cells have shown anti-diabetic effects in rodents and human. Although, its primary site of action consists in maintaining the gut barrier function, there are no study exploring if A. muciniphila controls glycemia via a gut to brain axis. Targeting the gut motility represents an alternative pathway to treat hyperglycemia. Here, we tested the impact of pasteurized A. muciniphila on gut motility, gut-brain axis and glucose metabolism.<br><br>METHODS: We used mice fed a 45% high-fat (HFD) treated or not with pasteurized A. muciniphila Muc[T] during 12 weeks. We measured the effects of the treatment on body weight gain, glucose metabolism (insulin, glycemia, glucose tolerance), gut contraction and enteric neurotransmitter release, and hypothalamic nitric oxide (NO) release.<br><br>RESULTS: We show that pasteurized A. muciniphila exerts positive effects on different metabolic parameters such as body weight, fat mass, insulin, glycemia and glucose tolerance. This could be explained by the ability of pasteurized A. muciniphila supplementation to decrease duodenal contraction and to increase hypothalamic NO release in HFD mice.<br><br>CONCLUSION: We demonstrate a novel mode of action of pasteurized A. muciniphila explaining its beneficial impact on the control of glycemia in a preclinical model of type 2 diabetes via gut-brain axis signaling.}, }
@article {pmid37498052, year = {2023}, author = {Huang, Z and Li, Y and Park, H and Ho, M and Bhardwaj, K and Sugimura, N and Lee, HW and Meng, H and Ebert, MP and Chao, K and Burgermeister, E and Bhatt, AP and Shetty, SA and Li, K and Wen, W and Zuo, T}, title = {Unveiling and harnessing the human gut microbiome in the rising burden of non-communicable diseases during urbanization.}, journal = {Gut microbes}, volume = {15}, number = {1}, pages = {2237645}, pmid = {37498052}, issn = {1949-0984}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; Urbanization ; *Noncommunicable Diseases/therapy/drug therapy ; *Microbiota ; *Probiotics ; Fecal Microbiota Transplantation ; Anti-Bacterial Agents/therapeutic use ; Dysbiosis/drug therapy ; Prebiotics ; }, abstract = {The world is witnessing a global increase in the urban population, particularly in developing Asian and African countries. Concomitantly, the global burden of non-communicable diseases (NCDs) is rising, markedly associated with the changing landscape of lifestyle and environment during urbanization. Accumulating studies have revealed the role of the gut microbiome in regulating the immune and metabolic homeostasis of the host, which potentially bridges external factors to the host (patho-)physiology. In this review, we discuss the rising incidences of NCDs during urbanization and their links to the compositional and functional dysbiosis of the gut microbiome. In particular, we elucidate the effects of urbanization-associated factors (hygiene/pollution, urbanized diet, lifestyles, the use of antibiotics, and early life exposure) on the gut microbiome underlying the pathogenesis of NCDs. We also discuss the potential and feasibility of microbiome-inspired and microbiome-targeted approaches as novel avenues to counteract NCDs, including fecal microbiota transplantation, diet modulation, probiotics, postbiotics, synbiotics, celobiotics, and precision antibiotics.}, }
@article {pmid37498047, year = {2023}, author = {Kandalai, S and Li, H and Zhang, N and Peng, H and Zheng, Q}, title = {The human microbiome and cancer: a diagnostic and therapeutic perspective.}, journal = {Cancer biology &amp; therapy}, volume = {24}, number = {1}, pages = {2240084}, pmid = {37498047}, issn = {1555-8576}, mesh = {Humans ; *Microbiota ; *Neoplasms/diagnosis/therapy ; Immunotherapy ; }, abstract = {Recent evidence has shown that the human microbiome is associated with various diseases, including cancer. The salivary microbiome, fecal microbiome, and circulating microbial DNA in blood plasma have all been used experimentally as diagnostic biomarkers for many types of cancer. The microbiomes present within local tissue, other regions, and tumors themselves have been shown to promote and restrict the development and progression of cancer, most often by affecting cancer cells or the host immune system. These microbes have also been shown to impact the efficacy of various cancer therapies, including radiation, chemotherapy, and immunotherapy. Here, we review the research advances focused on how microbes impact these different facets and why they are important to the clinical care of cancer. It is only by better understanding the roles these microbes play in the diagnosis, development, progression, and treatment of cancer, that we will be able to catch and treat cancer early.}, }
@article {pmid37484251, year = {2023}, author = {Bappy, MNI and Robin, TB and Prome, AA and Patil, RB and Moin, AT and Akter, R and Laskar, FS and Roy, A and Akter, H and Zinnah, KMA}, title = {Subtractive proteomics analysis to uncover the potent drug targets for distinctive drug design of Candidaauris.}, journal = {Heliyon}, volume = {9}, number = {6}, pages = {e17026}, pmid = {37484251}, issn = {2405-8440}, abstract = {Candida auris is a serious health concern of the current world that possesses a serious global health threat and is emerging at a high rate. Available antifungal drugs are failing to combat this pathogen as they are growing resistant to those drugs and some strains have already shown resistance to all three available antifungal drugs in the market. Hence, finding alternative therapies is essential for saving lives from this enemy. To make the development of new treatments easier, we conducted some in silico study of this pathogen to discover possible targets for drug design and also recommended some possible metabolites to test in vivo circumstances. The complete proteome of the representative strain was retrieved, and the duplicate, non-essential, human homologous, non-metabolic, and druggable proteins were then eliminated. As a result, out of a total of 5441 C. auris proteins, we were able to isolate three proteins (XP 028890156.1, XP 028891672.1, and XP 028891858.1) that are crucial for the pathogen's survival as well as host-non-homolog, metabolic, and unrelated proteins to the human microbiome. Their subcellular locations and interactions with a large number of proteins (10 proteins) further point to them being good candidates for therapeutic targets. Following in silico docking of 29 putative antifungals of plant origin against the three proteins we chose, Caledonixanthone E, Viniferin, Glaucine, and Jatrorrhizine were discovered to be the most effective means of inhibiting those proteins since they displayed higher binding affinities (ranging from -28.97 kcal/mol to -51.99 kcal/mol) than the control fluconazole (which ranged between -28.84 kcal/mol and -41.15 kcal/mol). According to the results of MD simulations and MM-PBSA calculations, Viniferin and Caledonixanthone E are the most effective ligands for the proteins XP 028890156.1, XP 028891672.1, and XP 028891858.1. Furthermore, they were predicted to be safe and also showed proper ADME properties.}, }
@article {pmid37480129, year = {2023}, author = {Coccolini, F and Sartelli, M and Sawyer, R and Rasa, K and Viaggi, B and Abu-Zidan, F and Soreide, K and Hardcastle, T and Gupta, D and Bendinelli, C and Ceresoli, M and Shelat, VG and Broek, RT and Baiocchi, GL and Moore, EE and Sall, I and Podda, M and Bonavina, L and Kryvoruchko, IA and Stahel, P and Inaba, K and Montravers, P and Sakakushev, B and Sganga, G and Ballestracci, P and Malbrain, MLNG and Vincent, JL and Pikoulis, M and Beka, SG and Doklestic, K and Chiarugi, M and Falcone, M and Bignami, E and Reva, V and Demetrashvili, Z and Di Saverio, S and Tolonen, M and Navsaria, P and Bala, M and Balogh, Z and Litvin, A and Hecker, A and Wani, I and Fette, A and De Simone, B and Ivatury, R and Picetti, E and Khokha, V and Tan, E and Ball, C and Tascini, C and Cui, Y and Coimbra, R and Kelly, M and Martino, C and Agnoletti, V and Boermeester, MA and De'Angelis, N and Chirica, M and Biffl, WL and Ansaloni, L and Kluger, Y and Catena, F and Kirkpatrick, AW}, title = {Source control in emergency general surgery: WSES, GAIS, SIS-E, SIS-A guidelines.}, journal = {World journal of emergency surgery : WJES}, volume = {18}, number = {1}, pages = {41}, pmid = {37480129}, issn = {1749-7922}, mesh = {Female ; Humans ; Male ; *Surgeons ; *Abdominal Cavity ; *Intraabdominal Infections ; }, abstract = {Intra-abdominal infections (IAI) are among the most common global healthcare challenges and they are usually precipitated by disruption to the gastrointestinal (GI) tract. Their successful management typically requires intensive resource utilization, and despite the best therapies, morbidity and mortality remain high. One of the main issues required to appropriately treat IAI that differs from the other etiologies of sepsis is the frequent requirement to provide physical source control. Fortunately, dramatic advances have been made in this aspect of treatment. Historically, source control was left to surgeons only. With new technologies non-surgical less invasive interventional procedures have been introduced. Alternatively, in addition to formal surgery open abdomen techniques have long been proposed as aiding source control in severe intra-abdominal sepsis. It is ironic that while a lack or even delay regarding source control clearly associates with death, it is a concept that remains poorly described. For example, no conclusive definition of source control technique or even adequacy has been universally accepted. Practically, source control involves a complex definition encompassing several factors including the causative event, source of infection bacteria, local bacterial flora, patient condition, and his/her eventual comorbidities. With greater understanding of the systemic pathobiology of sepsis and the profound implications of the human microbiome, adequate source control is no longer only a surgical issue but one that requires a multidisciplinary, multimodality approach. Thus, while any breach in the GI tract must be controlled, source control should also attempt to control the generation and propagation of the systemic biomediators and dysbiotic influences on the microbiome that perpetuate multi-system organ failure and death. Given these increased complexities, the present paper represents the current opinions and recommendations for future research of the World Society of Emergency Surgery, of the Global Alliance for Infections in Surgery of Surgical Infection Society Europe and Surgical Infection Society America regarding the concepts and operational adequacy of source control in intra-abdominal infections.}, }
@article {pmid37479864, year = {2023}, author = {Freitas, P and Silva, F and Sousa, JV and Ferreira, RM and Figueiredo, C and Pereira, T and Oliveira, HP}, title = {Machine learning-based approaches for cancer prediction using microbiome data.}, journal = {Scientific reports}, volume = {13}, number = {1}, pages = {11821}, pmid = {37479864}, issn = {2045-2322}, mesh = {Humans ; *Colonic Neoplasms/diagnosis ; *Rectal Neoplasms ; *Stomach Neoplasms/diagnosis ; Machine Learning ; *Microbiota/genetics ; }, abstract = {Emerging evidence of the relationship between the microbiome composition and the development of numerous diseases, including cancer, has led to an increasing interest in the study of the human microbiome. Technological breakthroughs regarding DNA sequencing methods propelled microbiome studies with a large number of samples, which called for the necessity of more sophisticated data-analytical tools to analyze this complex relationship. The aim of this work was to develop a machine learning-based approach to distinguish the type of cancer based on the analysis of the tissue-specific microbial information, assessing the human microbiome as valuable predictive information for cancer identification. For this purpose, Random Forest algorithms were trained for the classification of five types of cancer-head and neck, esophageal, stomach, colon, and rectum cancers-with samples provided by The Cancer Microbiome Atlas database. One versus all and multi-class classification studies were conducted to evaluate the discriminative capability of the microbial data across increasing levels of cancer site specificity, with results showing a progressive rise in difficulty for accurate sample classification. Random Forest models achieved promising performances when predicting head and neck, stomach, and colon cancer cases, with the latter returning accuracy scores above 90% across the different studies conducted. However, there was also an increased difficulty when discriminating esophageal and rectum cancers, failing to differentiate with adequate results rectum from colon cancer cases, and esophageal from head and neck and stomach cancers. These results point to the fact that anatomically adjacent cancers can be more complex to identify due to microbial similarities. Despite the limitations, microbiome data analysis using machine learning may advance novel strategies to improve cancer detection and prevention, and decrease disease burden.}, }
@article {pmid37479852, year = {2023}, author = {Ren, Q and Hill, JE}, title = {Rapid and accurate taxonomic classification of cpn60 amplicon sequence variants.}, journal = {ISME communications}, volume = {3}, number = {1}, pages = {77}, pmid = {37479852}, issn = {2730-6151}, abstract = {The "universal target" region of the gene encoding the 60 kDa chaperonin protein (cpn60, also known as groEL or hsp60) is a proven sequence barcode for bacteria and a useful target for marker gene amplicon-based studies of complex microbial communities. To date, identification of cpn60 sequence variants from microbiome studies has been accomplished by alignment of queries to a reference database. Naïve Bayesian classifiers offer an alternative identification method that provides variable rank classification and shorter analysis times. We curated a set of cpn60 barcode sequences to train the RDP classifier and tested its performance on data from previous human microbiome studies. Results showed that sequences accounting for 79%, 86% and 92% of the observations (read counts) in saliva, vagina and infant stool microbiome data sets were classified to the species rank. We also trained the QIIME 2 q2-feature-classifier on cpn60 sequence data and demonstrated that it gives results consistent with the standalone RDP classifier. Successful implementation of a naïve Bayesian classifier for cpn60 sequences will facilitate future microbiome studies and open opportunities to integrate cpn60 amplicon sequence identification into existing analysis pipelines.}, }
@article {pmid37479064, year = {2023}, author = {Bosch, B and Moutaharrik, S and Gazzaniga, A and Hiippala, K and Santos, HA and Maroni, A and Satokari, R}, title = {Development of a time-dependent oral colon delivery system of anaerobic Odoribacter splanchnicus for bacteriotherapy.}, journal = {European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V}, volume = {190}, number = {}, pages = {73-80}, doi = {10.1016/j.ejpb.2023.07.010}, pmid = {37479064}, issn = {1873-3441}, mesh = {*Inflammatory Bowel Diseases/metabolism ; Anaerobiosis ; Drug Delivery Systems ; Tablets/metabolism ; Anti-Inflammatory Agents/metabolism ; Humans ; Bacteroidetes ; Hydrogen-Ion Concentration ; *Colon/metabolism ; }, abstract = {Odoribacter (O.) splanchnicus is an anaerobic member of the human intestinal microbiota. Its decrease in abundance has been associated with inflammatory bowel disease (IBD), non-alcoholic fatty liver, and cystic fibrosis. Considering the anti-inflammatory properties of O. splanchnicus and its possible use for IBD, intestinal isolate O. splanchnicus 57 was here formulated for oral colonic release based on a time-dependent strategy. Freeze-drying protocol was determined to ensure O. splanchnicus 57 viability during the process. Disintegrating tablets, containing the freeze-dried O. splanchnicus 57, were manufactured by direct compression and coated by powder-layering technique with hydroxypropyl methylcellulose (Methocel™ E50) in a tangential-spray fluid bed. Eudragit® L was then applied by spray-coating in a top-spray fluid bed. Double-coated tablets were tested for release, showing gastric resistance properties and, as desired, lag phases of reproducible duration prior to release in phosphate buffer pH 6.8. The cell viability and anti-inflammatory activity of the strain were assessed after the main manufacturing steps. While freeze-drying did not affect bacterial viability, the tableting and coating processes were more stressful. Nonetheless, O. splanchnicus 57 cells survived manufacturing and the final formulations had 10[6]-10[7] CFU/g of viable cells. The strain kept its anti-inflammatory properties after tableting and coating, reducing Escherichia coli lipopolysaccharide-induced interleukin-8 cytokine release from HT-29 cells. Overall, O. splanchnicus 57 strain was formulated successfully for oral colon delivery, opening new ways to formulate pure cultures of single anaerobic strains or mixtures for oral delivery.}, }
@article {pmid37474544, year = {2023}, author = {Castellini, G and Cassioli, E and Vitali, F and Rossi, E and Dani, C and Melani, G and Flaccomio, D and D'Andria, M and Mejia Monroy, M and Galli, A and Cavalieri, D and Ricca, V and Bartolucci, GL and De Filippo, C}, title = {Gut microbiota metabolites mediate the interplay between childhood maltreatment and psychopathology in patients with eating disorders.}, journal = {Scientific reports}, volume = {13}, number = {1}, pages = {11753}, pmid = {37474544}, issn = {2045-2322}, mesh = {Humans ; Child ; Adolescent ; Young Adult ; *Gastrointestinal Microbiome ; *Feeding and Eating Disorders ; *Anorexia Nervosa/psychology ; Butyrates ; *Child Abuse ; }, abstract = {Eating disorders (EDs) are syndromes with a multifactorial etiopathogenesis, involving childhood traumatic experiences, as well as biological factors. Human microbiome has been hypothesised to play a fundamental role, impacting on emotion regulation, as well as with eating behaviours through its metabolites such as short chain fatty acids (SCFAs). The present study investigated the interactions between psychopathology of EDs, the gut microbiome and SCFAs resulting from bacterial community metabolic activities in a population of 47 patients with Anorexia Nervosa, Bulimia Nervosa, and Binge Eating Disorder and in healthy controls (HCs). Bacterial gut microbiota composition differences were found between subjects with EDs and HCs, especially in association with different pathological behaviours (binge-purge vs restricting). A mediation model of early trauma and ED-specific psychopathology linked reduction of microbial diversity to a typical microbiota-derived metabolite such as butyric acid. A possible interpretation for this model might be that childhood trauma represents a risk factor for gut dysbiosis and for a stable modification of mechanisms responsible for SCFAs production, and that this dysfunctional community is inherited in the passage from childhood to adulthood. These findings might open the way to novel interventions of butyric acid-like compounds as well as faecal transplant.}, }
@article {pmid37469430, year = {2023}, author = {Fernandez-Cantos, MV and Garcia-Morena, D and Yi, Y and Liang, L and Gómez-Vázquez, E and Kuipers, OP}, title = {Bioinformatic mining for RiPP biosynthetic gene clusters in Bacteroidales reveals possible new subfamily architectures and novel natural products.}, journal = {Frontiers in microbiology}, volume = {14}, number = {}, pages = {1219272}, pmid = {37469430}, issn = {1664-302X}, abstract = {The Bacteroidales order, widely distributed among diverse human populations, constitutes a key component of the human microbiota. Members of this Gram-negative order have been shown to modulate the host immune system, play a fundamental role in the gut's microbial food webs, or be involved in pathogenesis. Bacteria inhabiting such a complex environment as the human microbiome are expected to display social behaviors and, hence, possess factors that mediate cooperative and competitive interactions. Different types of molecules can mediate interference competition, including non-ribosomal peptides (NRPs), polyketides, and bacteriocins. The present study investigates the potential of Bacteroidales bacteria to biosynthesize class I bacteriocins, which are ribosomally synthesized and post-translationally modified peptides (RiPPs). For this purpose, 1,136 genome-sequenced strains from this order were mined using BAGEL4. A total of 1,340 areas of interest (AOIs) were detected. The most commonly identified enzymes involved in RiPP biosynthesis were radical S-adenosylmethionine (rSAM), either alone or in combination with other biosynthetic enzymes such as YcaO. A more comprehensive analysis of a subset of 9 biosynthetic gene clusters (BGCs) revealed a consistent association in Bacteroidales BGCs between peptidase-containing ATP-binding transporters (PCATs) and precursor peptides with GG-motifs. This finding suggests a possibly shared mechanism for leader peptide cleavage and transport of mature products. Notably, human metagenomic studies showed a high prevalence and abundance of the RiPP BGCs from Phocaeicola vulgatus and Porphyromonas gulae. The mature product of P. gulae BGC is hypothesized to display γ-thioether linkages and a C-terminal backbone amidine, a potential new combination of post-translational modifications (PTM). All these findings highlight the RiPP biosynthetic potential of Bacteroidales bacteria, as a rich source of novel peptide structures of possible relevance in the human microbiome context.}, }
@article {pmid37466413, year = {2024}, author = {Revankar, NA and Negi, PS}, title = {Biotics: An emerging food supplement for health improvement in the era of immune modulation.}, journal = {Nutrition in clinical practice : official publication of the American Society for Parenteral and Enteral Nutrition}, volume = {39}, number = {2}, pages = {311-329}, doi = {10.1002/ncp.11036}, pmid = {37466413}, issn = {1941-2452}, mesh = {Animals ; Humans ; *Gastrointestinal Microbiome ; Prebiotics ; *Probiotics/therapeutic use ; *Synbiotics ; Immunity ; }, abstract = {The involvement of the commensal microbiota in immune function is a multifold process. Biotics, such as probiotics, prebiotics, synbiotics, and paraprobiotics, have been subjected to animal and human trials demonstrating the association between gut microbes and immunity biomarkers leading to improvement in overall health. In recent years, studies on human microbiome interaction have established the multifarious role of biotics in maintaining overall health. The consumption of biotics has been extensively reported to help in maintaining microbial diversity, enhancing gut-associated mucosal immune homeostasis, and providing protection against a wide range of lifestyle disorders. However, the establishment of biotics as an alternative therapy for a range of health conditions is yet to be ascertained. Despite the fact that scientific literature has demonstrated the correlation between biotics and immune modulation, most in vivo and in vitro reports are inconclusive on the dosage required. This review provides valuable insights into the immunomodulatory effects of biotics consumption based on evidence obtained from animal models and clinical trials. Furthermore, we highlight the optimal dosages of biotics that have been reported to deliver maximum health benefits. By identifying critical research gaps, we have suggested a roadmap for future investigations to advance our understanding of the intricate crosstalk between biotics and immune homeostasis.}, }
@article {pmid37460001, year = {2023}, author = {Boopathi, S and Priya, PS and Haridevamuthu, B and Nayak, SPRR and Chandrasekar, M and Arockiaraj, J and Jia, AQ}, title = {Expanding germ-organ theory: Understanding non-communicable diseases through enterobacterial translocation.}, journal = {Pharmacological research}, volume = {194}, number = {}, pages = {106856}, doi = {10.1016/j.phrs.2023.106856}, pmid = {37460001}, issn = {1096-1186}, mesh = {Humans ; Enterobacteriaceae ; *Noncommunicable Diseases ; *Gastrointestinal Microbiome ; Inflammation/microbiology ; *Microbiota ; }, abstract = {Diverse microbial communities colonize different habitats of the human body, including gut, oral cavity, nasal cavity and tissues. These microbial communities are known as human microbiome, plays a vital role in maintaining the health. However, changes in the composition and functions of human microbiome can result in chronic low-grade inflammation, which can damage the epithelial cells and allows pathogens and their toxic metabolites to translocate into other organs such as the liver, heart, and kidneys, causing metabolic inflammation. This dysbiosis of human microbiome has been directly linked to the onset of several non-communicable diseases. Recent metabolomics studies have revealed that pathogens produce several uraemic toxins. These metabolites can serve as inter-kingdom signals, entering the circulatory system and altering host metabolism, thereby aggravating a variety of diseases. Interestingly, Enterobacteriaceae, a critical member of Proteobacteria, has been commonly associated with several non-communicable diseases, and the abundance of this family has been positively correlated with uraemic toxin production. Hence, this review provides a comprehensive overview of Enterobacterial translocation and their metabolites role in non-communicable diseases. This understanding may lead to the identification of novel biomarkers for each metabolic disease as well as the development of novel therapeutic drugs.}, }
@article {pmid37457960, year = {2023}, author = {Dame-Teixeira, N and Do, T}, title = {Editorial: Rising stars in bacteria and host: 2022.}, journal = {Frontiers in cellular and infection microbiology}, volume = {13}, number = {}, pages = {1240952}, pmid = {37457960}, issn = {2235-2988}, mesh = {*Bacteria ; *Microbiota ; }, }
@article {pmid37457284, year = {2023}, author = {Lugones-Sánchez, C and Santos-Mínguez, S and Salvado, R and González-Sánchez, S and Tamayo-Morales, O and Hoya-González, A and Ramírez-Manent, JI and Magallón-Botaya, R and Quesada-Rico, JA and Garcia-Cubillas, MD and Rodríguez-Sánchez, E and Gómez-Marcos, MA and Benito-Sanchez, R and Mira, A and Hernandez-Rivas, JM and Garcia-Ortiz, L and , }, title = {Lifestyles, arterial aging, and its relationship with the intestinal and oral microbiota (MIVAS III study): a research protocol for a cross-sectional multicenter study.}, journal = {Frontiers in public health}, volume = {11}, number = {}, pages = {1164453}, pmid = {37457284}, issn = {2296-2565}, mesh = {Humans ; Middle Aged ; Aged ; Cross-Sectional Studies ; *Cardiovascular Diseases/epidemiology ; Blood Pressure/physiology ; Pulse Wave Analysis/methods ; RNA, Ribosomal, 16S ; Aging ; Life Style ; *Diet, Mediterranean ; *Microbiota ; Multicenter Studies as Topic ; }, abstract = {BACKGROUND: The microbiota is increasingly recognized as a significant factor in the pathophysiology of many diseases, including cardiometabolic diseases, with lifestyles probably exerting the greatest influence on the composition of the human microbiome. The main objectives of the study are to analyze the association of lifestyles (diet, physical activity, tobacco, and alcohol) with the gut and oral microbiota, arterial aging, and cognitive function in subjects without cardiovascular disease in the Iberian Peninsula. In addition, the study will examine the mediating role of the microbiome in mediating the association between lifestyles and arterial aging as well as cognitive function.<br><br>METHODS AND ANALYSIS: MIVAS III is a multicenter cross-sectional study that will take place in the Iberian Peninsula. One thousand subjects aged between 45 and 74 years without cardiovascular disease will be selected. The main variables are demographic information, anthropometric measurements, and habits (tobacco and alcohol). Dietary patterns will be assessed using a frequency consumption questionnaire (FFQ) and the Mediterranean diet adherence questionnaire. Physical activity levels will be evaluated using the International Physical Activity Questionnaire (IPAQ), Marshall Questionnaire, and an Accelerometer (Actigraph). Body composition will be measured using the Inbody 230 impedance meter. Arterial aging will be assessed through various means, including measuring medium intimate carotid thickness using the Sonosite Micromax, conducting analysis with pulse wave velocity (PWA), and measuring pulse wave velocity (cf-PWV) using the Sphygmocor System. Additional cardiovascular indicators such as Cardio Ankle Vascular Index (CAVI), ba-PWV, and ankle-brachial index (Vasera VS-2000[&#xae;]) will also be examined. The study will analyze the intestinal microbiota using the OMNIgene GUT kit (OMR-200) and profile the microbiome through massive sequencing of the 16S rRNA gene. Linear discriminant analysis (LDA), effect size (LEfSe), and compositional analysis, such as ANCOM-BC, will be used to identify differentially abundant taxa between groups. After rarefying the samples, further analyses will be conducted using MicrobiomeAnalyst and R v.4.2.1 software. These analyses will include various aspects, such as assessing &#x3b1; and &#x3b2; diversity, conducting abundance profiling, and performing clustering analysis.<br><br>DISCUSSION: Lifestyle acts as a modifier of microbiota composition. However, there are no conclusive results demonstrating the mediating effect of the microbiota in the relationship between lifestyles and cardiovascular diseases. Understanding this relationship may facilitate the implementation of strategies for improving population health by modifying the gut and oral microbiota.<br><br>TRIAL REGISTRATION: clinicaltrials.gov/ct2/show/NCT04924907, ClinicalTrials.gov, identifier: NCT04924907. Registered on 21 April 2021.}, }
@article {pmid37445613, year = {2023}, author = {Satala, D and Bednarek, A and Kozik, A and Rapala-Kozik, M and Karkowska-Kuleta, J}, title = {The Recruitment and Activation of Plasminogen by Bacteria-The Involvement in Chronic Infection Development.}, journal = {International journal of molecular sciences}, volume = {24}, number = {13}, pages = {}, pmid = {37445613}, issn = {1422-0067}, mesh = {Humans ; *Plasminogen/metabolism ; *Persistent Infection ; Bacteria/metabolism ; Fibrinolysin/metabolism ; Fibrinolysis ; }, abstract = {The development of infections caused by pathogenic bacteria is largely related to the specific properties of the bacterial cell surface and extracellular hydrolytic activity. Furthermore, a significant role of hijacking of host proteolytic cascades by pathogens during invasion should not be disregarded during consideration of the mechanisms of bacterial virulence. This is the key factor for the pathogen evasion of the host immune response, tissue damage, and pathogen invasiveness at secondary infection sites after initial penetration through tissue barriers. In this review, the mechanisms of bacterial impact on host plasminogen-the precursor of the important plasma serine proteinase, plasmin-are characterized, principally focusing on cell surface exposition of various proteins, responsible for binding of this host (pro)enzyme and its activators or inhibitors, as well as the fibrinolytic system activation tactics exploited by different bacterial species, not only pathogenic, but also selected harmless residents of the human microbiome. Additionally, the involvement of bacterial factors that modulate the process of plasminogen activation and fibrinolysis during periodontitis is also described, providing a remarkable example of a dual use of this host system in the development of chronic diseases.}, }
@article {pmid37437419, year = {2023}, author = {Gundogdu, A and Nalbantoglu, OU}, title = {The role of the Mediterranean diet in modulating the gut microbiome: A review of current evidence.}, journal = {Nutrition (Burbank, Los Angeles County, Calif.)}, volume = {114}, number = {}, pages = {112118}, doi = {10.1016/j.nut.2023.112118}, pmid = {37437419}, issn = {1873-1244}, mesh = {Humans ; *Diet, Mediterranean ; *Gastrointestinal Microbiome ; Nutrients ; Nutritional Status ; Micronutrients ; }, abstract = {The Mediterranean diet (MedDiet) is recognized as one of the United Nations Educational, Scientific and Cultural Organization Intangible Cultural Heritage assets associated with lower rates of cardiometabolic diseases; lower prevalence of cancer, Alzheimer's disease, depression, and onset of inflammatory bowel disease; and more generally low-grade inflammation and mortality risks. Beyond being an input source of beneficial micronutrients, it recently has been discovered that the MedDiet plays a role in a more complex human microbiome-mediated mechanism. An interesting hypothesis suggests a bidirectional relationship between the MedDiet and the gut microbiome, where gut microbiota assembly and biosynthetic capacity are responsive to the diet; in return, the microbiome-reachable nutrients shape and modulate the microbiome toward a characteristic probiotic state. It can be speculated that that primary health benefits of the MedDiet exerted via the gut microbiome are mediated by the bioactive compounds transformed by the microbiome. Furthermore, it is possible that additional probiotic properties of the organisms promoted by diet adherence have secondary benefits. As more detailed omic-based studies take place, more evidence on the MedDiet as a core generic probiotic microbiome modulation strategy surface. However, individual-specific microbiome compositions might impose personal variations on the diet outcome. Therefore, a prospective strategy of a fine-tuned precision nutrition approach might deliver optimized benefits of the MedDiet.}, }
@article {pmid37437088, year = {2023}, author = {Robben, M and Nasr, MS and Das, A and Veerla, JP and Huber, M and Jaworski, J and Weidanz, J and Luber, J}, title = {Comparison of the Strengths and Weaknesses of Machine Learning Algorithms and Feature Selection on KEGG Database Microbial Gene Pathway Annotation and Its Effects on Reconstructed Network Topology.}, journal = {Journal of computational biology : a journal of computational molecular cell biology}, volume = {30}, number = {7}, pages = {766-782}, doi = {10.1089/cmb.2022.0370}, pmid = {37437088}, issn = {1557-8666}, mesh = {Humans ; Molecular Sequence Annotation ; *Algorithms ; *Genes, Microbial ; Neural Networks, Computer ; Machine Learning ; }, abstract = {The development of tools for the annotation of genes from newly sequenced species has not evolved much from homologous alignment to prior annotated species. While the quality of gene annotations continues to decline as we sequence and assemble more evolutionary distant gut microbiome species, machine learning presents a high quality alternative to traditional techniques. In this study, we investigate the relative performance of common classical and nonclassical machine learning algorithms in the problem of gene annotation using human microbiome-associated species genes from the KEGG database. The majority of the ensemble, clustering, and deep learning algorithms that we investigated showed higher prediction accuracy than CD-Hit in predicting partial KEGG function. Motif-based, machine-learning methods of annotation in new species were faster and had higher precision-recall than methods of homologous alignment or orthologous gene clustering. Gradient boosted ensemble methods and neural networks also predicted higher connectivity in reconstructed KEGG pathways, finding twice as many new pathway interactions than blast alignment. The use of motif-based, machine-learning algorithms in annotation software will allow researchers to develop powerful tools to interact with bacterial microbiomes in ways previously unachievable through homologous sequence alignment alone.}, }
@article {pmid37429848, year = {2023}, author = {Sadhu, S and Dalal, R and Dandotiya, J and Binayke, A and Singh, V and Tripathy, MR and Das, V and Goswami, S and Kumar, S and Rizvi, ZA and Awasthi, A}, title = {IL-9 aggravates SARS-CoV-2 infection and exacerbates associated airway inflammation.}, journal = {Nature communications}, volume = {14}, number = {1}, pages = {4060}, pmid = {37429848}, issn = {2041-1723}, mesh = {Inflammation ; SARS-CoV-2 ; Thymus Gland/abnormalities ; Immunologic Deficiency Syndromes ; Angiotensin-Converting Enzyme 2 ; *Interleukin-9/genetics ; Animals ; Mice ; *COVID-19 ; }, abstract = {SARS-CoV-2 infection is known for causing broncho-alveolar inflammation. Interleukin 9 (IL-9) induces airway inflammation and bronchial hyper responsiveness in respiratory viral illnesses and allergic inflammation, however, IL-9 has not been assigned a pathologic role in COVID-19. Here we show, in a K18-hACE2 transgenic (ACE2.Tg) mouse model, that IL-9 contributes to and exacerbates viral spread and airway inflammation caused by SARS-CoV-2 infection. ACE2.Tg mice with CD4[+] T cell-specific deficiency of the transcription factor Forkhead Box Protein O1 (Foxo1) produce significantly less IL-9 upon SARS-CoV-2 infection than the wild type controls and they are resistant to the severe inflammatory disease that characterises the control mice. Exogenous IL-9 increases airway inflammation in Foxo1-deficient mice, while IL-9 blockade reduces and suppresses airway inflammation in SARS-CoV-2 infection, providing further evidence for a Foxo1-Il-9 mediated Th cell-specific pathway playing a role in COVID-19. Collectively, our study provides mechanistic insight into an important inflammatory pathway in SARS-CoV-2 infection, and thus represents proof of principle for the development of host-directed therapeutics to mitigate disease severity.}, }
@article {pmid37426026, year = {2023}, author = {Eggers, S and Midya, V and Bixby, M and Gennings, C and Torres-Olascoaga, LA and Walker, RW and Wright, RO and Arora, M and Téllez-Rojo, MM}, title = {Prenatal lead exposure is negatively associated with the gut microbiome in childhood.}, journal = {Frontiers in microbiology}, volume = {14}, number = {}, pages = {1193919}, pmid = {37426026}, issn = {1664-302X}, support = {U2C ES026555/ES/NIEHS NIH HHS/United States ; R00 ES032884/ES/NIEHS NIH HHS/United States ; K99 ES032884/ES/NIEHS NIH HHS/United States ; R01 ES013744/ES/NIEHS NIH HHS/United States ; UL1 TR004419/TR/NCATS NIH HHS/United States ; }, abstract = {BACKGROUND: Metal exposures are associated with gut microbiome (GM) composition and function, and exposures early in development may be particularly important. Considering the role of the GM in association with many adverse health outcomes, understanding the relationship between prenatal metal exposures and the GM is critically important. However, there is sparse knowledge of the association between prenatal metal exposure and GM later in childhood.<br><br>OBJECTIVES: This analysis aims to identify associations between prenatal lead (Pb) exposure and GM composition and function in children 9-11 years old.<br><br>METHODS: Data come from the Programming Research in Obesity, Growth, Environment and Social Stressors (PROGRESS) cohort based in Mexico City, Mexico. Prenatal metal concentrations were measured in maternal whole blood drawn during the second and third trimesters of pregnancy. Stool samples collected at 9-11 years old underwent metagenomic sequencing to assess the GM. This analysis uses multiple statistical modeling approaches, including linear regression, permutational analysis of variance, weighted quantile sum regression (WQS), and individual taxa regressions, to estimate the association between maternal blood Pb during pregnancy and multiple aspects of the child GM at 9-11 years old, adjusting for relevant confounders.<br><br>RESULTS: Of the 123 child participants in this pilot data analysis, 74 were male and 49 were female. Mean prenatal maternal blood Pb was 33.6 (SE&#x2009;=&#x2009;2.1) ug/L and 34.9 (SE&#x2009;=&#x2009;2.1) ug/L at second and third trimesters, respectively. Analysis suggests a consistent negative relationship between prenatal maternal blood Pb and the GM at age 9-11, including measures of alpha and beta diversity, microbiome mixture analysis, and individual taxa. The WQS analysis showed a negative association between prenatal Pb exposure and the gut microbiome, for both second and third trimester exposures (2T&#x3b2;&#x2009;=&#x2009;-0.17, 95%CI&#x2009;=&#x2009;[-0.46,0.11]; 3T&#x3b2;&#x2009;=&#x2009;-0.17, 95%CI&#x2009;=&#x2009;[-0.44,0.10]). Ruminococcus gnavus, Bifidobacterium longum, Alistipes indistinctus, Bacteroides caccae, and Bifidobacterium bifidum all had weights above the importance threshold from 80% or more of the WQS repeated holdouts in association with both second and third trimester Pb exposure.<br><br>DISCUSSION: Pilot data analysis suggests a negative association between prenatal Pb exposure and the gut microbiome later in childhood; however, additional investigation is needed.}, }
@article {pmid37414899, year = {2023}, author = {Routy, B and Lenehan, JG and Miller, WH and Jamal, R and Messaoudene, M and Daisley, BA and Hes, C and Al, KF and Martinez-Gili, L and Punčochář, M and Ernst, S and Logan, D and Belanger, K and Esfahani, K and Richard, C and Ninkov, M and Piccinno, G and Armanini, F and Pinto, F and Krishnamoorthy, M and Figueredo, R and Thebault, P and Takis, P and Magrill, J and Ramsay, L and Derosa, L and Marchesi, JR and Parvathy, SN and Elkrief, A and Watson, IR and Lapointe, R and Segata, N and Haeryfar, SMM and Mullish, BH and Silverman, MS and Burton, JP and Maleki Vareki, S}, title = {Fecal microbiota transplantation plus anti-PD-1 immunotherapy in advanced melanoma: a phase I trial.}, journal = {Nature medicine}, volume = {29}, number = {8}, pages = {2121-2132}, pmid = {37414899}, issn = {1546-170X}, support = {MC_PC_12025/MRC_/Medical Research Council/United Kingdom ; PJT &#x2013; 156295//CIHR/Canada ; MOP 389137//CIHR/Canada ; PJT-178341//CIHR/Canada ; }, mesh = {Animals ; Mice ; *Fecal Microbiota Transplantation/methods ; Immune Checkpoint Inhibitors ; Feces/microbiology ; *Melanoma/therapy ; Immunotherapy ; Treatment Outcome ; }, abstract = {Fecal microbiota transplantation (FMT) represents a potential strategy to overcome resistance to immune checkpoint inhibitors in patients with refractory melanoma; however, the role of FMT in first-line treatment settings has not been evaluated. We conducted a multicenter phase I trial combining healthy donor FMT with the PD-1 inhibitors nivolumab or pembrolizumab in 20 previously untreated patients with advanced melanoma. The primary end point was safety. No grade 3 adverse events were reported from FMT alone. Five patients (25%) experienced grade 3 immune-related adverse events from combination therapy. Key secondary end points were objective response rate, changes in gut microbiome composition and systemic immune and metabolomics analyses. The objective response rate was 65% (13 of 20), including four (20%) complete responses. Longitudinal microbiome profiling revealed that all patients engrafted strains from their respective donors; however, the acquired similarity between donor and patient microbiomes only increased over time in responders. Responders experienced an enrichment of immunogenic and a loss of deleterious bacteria following FMT. Avatar mouse models confirmed the role of healthy donor feces in increasing anti-PD-1 efficacy. Our results show that FMT from healthy donors is safe in the first-line setting and warrants further investigation in combination with immune checkpoint inhibitors. ClinicalTrials.gov identifier NCT03772899 .}, }
@article {pmid37409975, year = {2023}, author = {Pratap Singh, R and Kumari, N and Gupta, S and Jaiswal, R and Mehrotra, D and Singh, S and Mukherjee, S and Kumar, R}, title = {Intratumoral Microbiota Changes with Tumor Stage and Influences the Immune Signature of Oral Squamous Cell Carcinoma.}, journal = {Microbiology spectrum}, volume = {11}, number = {4}, pages = {e0459622}, pmid = {37409975}, issn = {2165-0497}, mesh = {Humans ; *Carcinoma, Squamous Cell/pathology ; Squamous Cell Carcinoma of Head and Neck ; *Mouth Neoplasms ; RNA, Ribosomal, 16S/genetics ; *Microbiota ; *Head and Neck Neoplasms ; Tumor Microenvironment ; }, abstract = {Characterization of the oral microbiota profile through various studies has shown an association between the microbiome and oral cancer; however, stage-specific determinants of dynamic changes in microbial communities of oral cancer remain elusive. Additionally, the influence of the intratumoral microbiota on the intratumoral immune system remains largely unexplored. Therefore, this study aims to stratify microbial abundance in the early-onset and subsequent stages of oral cancer and analyze their influence on clinical-pathological and immunological features. The microbiome composition of tissue biopsy samples was identified using 16S rRNA amplicon sequencing, while intratumoral and systemic immune profiling was done with flow cytometry and immunohistochemistry-based analysis. The bacterial composition differed significantly among precancer, early cancer, and late cancer stages with the enrichment of genera Capnocytophaga, Fusobacterium, and Treponema in the cancer group, while Streptococcus and Rothia were enriched in the precancer group. Late cancer stages were significantly associated with Capnocytophaga with high predicting accuracy, while Fusobacterium was associated with early stages of cancer. A dense intermicrobial and microbiome-immune network was observed in the precancer group. At the cellular level, intratumoral immune cell infiltration of B cells and T cells (CD4[+] and CD8[+]) was observed with enrichment of the effector memory phenotype. Naive and effector subsets of tumor-infiltrating lymphocytes (TILs) and related gene expression were found to be distinctly associated with bacterial communities; most importantly, highly abundant bacterial genera of the tumor microenvironment were either negatively correlated or not associated with the effector lymphocytes, which led to the conclusion that the tumor microenvironment favors an immunosuppressive and nonimmunogenic microbiota. IMPORTANCE The gut microbiome has been explored extensively for its importance in the modulation of systemic inflammation and immune response; in contrast, the intratumoral microbiome is less studied for its influence on immunity in cancer. Given the established correlation between intratumoral lymphocyte infiltration and patient survival in cases of solid tumors, it was pertinent to explore the extrinsic factor influencing immune cell infiltration in the tumor. Modulation of intratumoral microbiota could have a beneficial effect on the antitumor immune response. This study stratifies the microbial profile of oral squamous cell carcinoma starting from precancer to late-stage cancer and provides evidence for their immunomodulatory role in the tumor microenvironment. Our results suggest combining microbiome study with immunological signatures of tumors for their prognostic and diagnostic application.}, }
@article {pmid37409956, year = {2023}, author = {Montelongo Hernandez, C and Putonti, C and Wolfe, AJ}, title = {Urinary Plasmids Reduce Permissivity to Coliphage Infection.}, journal = {Microbiology spectrum}, volume = {11}, number = {4}, pages = {e0130923}, pmid = {37409956}, issn = {2165-0497}, mesh = {Humans ; Escherichia coli/genetics ; Plasmids/genetics ; Coliphages/genetics ; *Bacteriophages/genetics ; *Escherichia coli Infections/microbiology ; *Urinary Tract ; Bacteria/genetics ; Anti-Bacterial Agents ; }, abstract = {The microbial community of the urinary tract (urinary microbiota or urobiota) has been associated with human health. Bacteriophages (phages) and plasmids present in the urinary tract, like in other niches, may shape urinary bacterial dynamics. While urinary Escherichia coli strains associated with urinary tract infection (UTI) and their phages have been catalogued for the urobiome, bacterium-plasmid-phage interactions have yet to be explored. In this study, we characterized urinary E. coli plasmids and their ability to decrease permissivity to E. coli phage (coliphage) infection. Putative F plasmids were predicted in 47 of 67 urinary E. coli isolates, and most of these plasmids carried genes that encode toxin-antitoxin (TA) modules, antibiotic resistance, and/or virulence. Urinary E. coli plasmids, from urinary microbiota strains UMB0928 and UMB1284, were conjugated into E. coli K-12 strains. These transconjugants included genes for antibiotic resistance and virulence, and they decreased permissivity to coliphage infection by the laboratory phage P1vir and the urinary phages Greed and Lust. Plasmids in one transconjugant were maintained in E. coli K-12 for up to 10 days in the absence of antibiotic resistance selection; this included the maintenance of the antibiotic resistance phenotype and decreased permissivity to phage. Finally, we discuss how F plasmids present in urinary E. coli strains could play a role in coliphage dynamics and the maintenance of antibiotic resistance in urinary E. coli. IMPORTANCE The urinary tract contains a resident microbial community called the urinary microbiota or urobiota. Evidence exists that it is associated with human health. Bacteriophages (phages) and plasmids present in the urinary tract, like in other niches, may shape urinary bacterial dynamics. Bacterium-plasmid-phage interactions have been studied primarily in laboratory settings and are yet to be thoroughly tested in complex communities. This is especially true of the urinary tract, where the bacterial genetic determinants of phage infection are not well understood. In this study, we characterized urinary E. coli plasmids and their ability to decrease permissivity to E. coli phage (coliphage) infection. Urinary E. coli plasmids, encoding antibiotic resistance and transferred by conjugation into naive laboratory E. coli K-12 strains, decreased permissivity to coliphage infection. We propose a model by which urinary plasmids present in urinary E. coli strains could help to decrease phage infection susceptibility and maintain the antibiotic resistance of urinary E. coli. This has consequences for phage therapy, which could inadvertently select for plasmids that encode antibiotic resistance.}, }
@article {pmid37404032, year = {2023}, author = {Deschênes, T and Tohoundjona, FWE and Plante, PL and Di Marzo, V and Raymond, F}, title = {Gene-based microbiome representation enhances host phenotype classification.}, journal = {mSystems}, volume = {8}, number = {4}, pages = {e0053123}, pmid = {37404032}, issn = {2379-5077}, mesh = {Humans ; *Diabetes Mellitus, Type 2/genetics ; *Microbiota/genetics ; Metagenome ; *Gastrointestinal Microbiome/genetics ; Phenotype ; }, abstract = {With the concomitant advances in both the microbiome and machine learning fields, the gut microbiome has become of great interest for the potential discovery of biomarkers to be used in the classification of the host health status. Shotgun metagenomics data derived from the human microbiome is composed of a high-dimensional set of microbial features. The use of such complex data for the modeling of host-microbiome interactions remains a challenge as retaining de novo content yields a highly granular set of microbial features. In this study, we compared the prediction performances of machine learning approaches according to different types of data representations derived from shotgun metagenomics. These representations include commonly used taxonomic and functional profiles and the more granular gene cluster approach. For the five case-control datasets used in this study (Type 2 diabetes, obesity, liver cirrhosis, colorectal cancer, and inflammatory bowel disease), gene-based approaches, whether used alone or in combination with reference-based data types, allowed improved or similar classification performances as the taxonomic and functional profiles. In addition, we show that using subsets of gene families from specific functional categories of genes highlight the importance of these functions on the host phenotype. This study demonstrates that both reference-free microbiome representations and curated metagenomic annotations can provide relevant representations for machine learning based on metagenomic data. IMPORTANCE Data representation is an essential part of machine learning performance when using metagenomic data. In this work, we show that different microbiome representations provide varied host phenotype classification performance depending on the dataset. In classification tasks, untargeted microbiome gene content can provide similar or improved classification compared to taxonomical profiling. Feature selection based on biological function also improves classification performance for some pathologies. Function-based feature selection combined with interpretable machine learning algorithms can generate new hypotheses that can potentially be assayed mechanistically. This work thus proposes new approaches to represent microbiome data for machine learning that can potentiate the findings associated with metagenomic data.}, }
@article {pmid37401755, year = {2023}, author = {Ronkainen, A and Khan, I and Krzyżewska-Dudek, E and Hiippala, K and Freitag, TL and Satokari, R}, title = {In vitro adhesion, pilus expression, and in vivo amelioration of antibiotic-induced microbiota disturbance by Bifidobacterium spp. strains from fecal donors.}, journal = {Gut microbes}, volume = {15}, number = {1}, pages = {2229944}, pmid = {37401755}, issn = {1949-0984}, mesh = {Animals ; Mice ; Anti-Bacterial Agents/pharmacology ; Bifidobacterium ; *Gastrointestinal Microbiome ; RNA, Ribosomal, 16S ; *Clostridioides difficile ; Mice, Inbred C57BL ; Feces/microbiology ; Fecal Microbiota Transplantation ; *Microbiota ; *Clostridium Infections/microbiology ; }, abstract = {Fecal microbiota transplantation (FMT) is used routinely to treat recurrent Clostridioides difficile infection (rCDI) and investigated as a treatment for numerous conditions associated with gut microbiota alterations. Metagenomic analyses have indicated that recipient colonization by donor bacteria may be associated with favorable clinical outcomes. Bifidobacteria are abundant gut commensals associated with health. We have previously demonstrated that Bifidobacterium strains transferred in FMT can colonize recipients in long term, at least for a year, and recovered such strains by cultivation. This study addressed in vitro adhesion and pilus gene expression of long-term colonizing Bifidobacterium strains from FMT donors as well as in vivo colonization and capability to ameliorate antibiotic-induced microbiota disturbance. RNA-Seq differential gene expression analysis showed that the strongly adherent B. longum strains DY_pv11 and DX_pv23 expressed tight adherence and sortase-dependent pilus genes, respectively. Two B. longum strains, adherent DX_pv23 and poorly adhering DX_pv18, were selected to address in vivo colonization and efficacy to restore antibiotic-disturbed microbiota in C57BL/6 murine model. DX_pv23 colonized mice transiently with a rate comparable to that of the B. animalis BB-12 used as a reference. Although long-term colonization was not observed with any of the three strains, 16S rRNA gene profiling revealed that oral administration of DX_pv23 enhanced the recovery of antibiotic-disturbed microbiota to the original configuration significantly better than the other strains. The findings suggest that selected strains from FMT donors, such as DX_pv23 in this study, may have therapeutic potential by in vitro expression of colonization factors and boosting endogenous gut microbiota.}, }
@article {pmid37401478, year = {2023}, author = {Riekkinen, M and Kajova, M and Eriksson, M and Luukkainen, A and Holmberg, V and Aro, T and Pakkanen, SH and Miettinen, S and Montonen, R and Smura, T and Lääveri, T and Kantele, A}, title = {Superspreading of SARS-CoV-2 Omicron BA.2.23 among vaccinated Finnish adults: symptomatic COVID-19 only contracted by those without recent infection.}, journal = {Epidemiology and infection}, volume = {151}, number = {}, pages = {e113}, pmid = {37401478}, issn = {1469-4409}, mesh = {Humans ; *COVID-19/prevention &amp; control ; SARS-CoV-2/genetics ; Finland/epidemiology ; Disease Outbreaks ; Fever ; }, abstract = {An outbreak of SARS-CoV-2 was confirmed after an academic party in Helsinki, Finland, in 2022. All 70 guests were requested to fill in follow-up questionnaires; serologic analyses and whole-genome sequencing (WGS) were conducted when possible.Of those participating - all but one with ≥3 vaccine doses - 21/53 (40%) had test-confirmed symptomatic COVID-19: 7% of those with earlier episodes and 76% of those without. Half (11/21) were febrile, but none needed hospitalisation. WGS revealed subvariant BA.2.23.Compared to vaccination alone, our data suggest remarkable protection by hybrid immunity against symptomatic infection, particularly in instances of recent infections with homologous variants.}, }
@article {pmid37400581, year = {2023}, author = {El Tekle, G and Garrett, WS}, title = {Bacteria in cancer initiation, promotion and progression.}, journal = {Nature reviews. Cancer}, volume = {23}, number = {9}, pages = {600-618}, pmid = {37400581}, issn = {1474-1768}, support = {R01 CA154426/CA/NCI NIH HHS/United States ; C10674/A27140/CRUK_/Cancer Research UK/United Kingdom ; }, mesh = {Humans ; *Neoplasms/etiology ; *Microbiota ; *Gastrointestinal Microbiome ; Bacteria ; Immune System ; Tumor Microenvironment ; }, abstract = {Cancer cells originate from a series of acquired genetic mutations that can drive their uncontrolled cell proliferation and immune evasion. Environmental factors, including the microorganisms that colonize the human body, can shift the metabolism, growth pattern and function of neoplastic cells and shape the tumour microenvironment. Dysbiosis of the gut microbiome is now recognized as a hallmark of cancer by the scientific community. However, only a few microorganisms have been identified that directly initiate tumorigenesis or skew the immune system to generate a tumour-permissive milieu. Over the past two decades, research on the human microbiome and its functionalities within and across individuals has revealed microbiota-focused strategies for health and disease. Here, we review the evolving understanding of the mechanisms by which the microbiota acts in cancer initiation, promotion and progression. We explore the roles of bacteria in gastrointestinal tract malignancies and cancers of the lung, breast and prostate. Finally, we discuss the promises and limitations of targeting or harnessing bacteria in personalized cancer prevention, diagnostics and treatment.}, }
@article {pmid37399600, year = {2023}, author = {Jokela, R and Ponsero, AJ and Dikareva, E and Wei, X and Kolho, KL and Korpela, K and de Vos, WM and Salonen, A}, title = {Sources of gut microbiota variation in a large longitudinal Finnish infant cohort.}, journal = {EBioMedicine}, volume = {94}, number = {}, pages = {104695}, pmid = {37399600}, issn = {2352-3964}, mesh = {Humans ; *Gastrointestinal Microbiome/genetics ; Infant ; Finland ; Female ; *RNA, Ribosomal, 16S/genetics ; Longitudinal Studies ; Male ; *Feces/microbiology ; Infant, Newborn ; Bacteria/genetics/classification/isolation &amp; purification ; Biodiversity ; }, abstract = {BACKGROUND: Although the infant gut microbiota has been extensively studied, comprehensive assessment on the microbiota determinants including technical variables has not been performed in large infant cohorts.<br><br>METHODS: We studied the effect of 109 variables on the 16S rRNA gene amplicon-based gut microbiota profiles of infants sampled longitudinally from three weeks to two years of life in the Finnish HELMi birth cohort. Spot faecal samples from both parents were included for intra-family analyses, totalling to 7657 samples from 985 families that were evaluated for beta-diversity patterns using permutational multivariate analysis on Bray-Curtis distances, and differential abundance testing and alpha-diversity for variables of interest. We also assessed the effect of different taxonomic levels and distance methods.<br><br>FINDINGS: In time point-specific models, the largest share of variation explained, up to 2-6%, were seen in decreasing order for the DNA extraction batch, delivery mode and related perinatal exposures, defecation frequency and parity/siblings. Variables describing the infant gastrointestinal function were continuously important during the first two years, reflecting changes in e.g., feeding habits. The effect of parity/siblings on infant microbiota was modified by birth mode and exposure to intrapartum antibiotics, exemplifying the tight interlinkage of perinatal factors relevant for infant microbiota research. In total, up to 19% of the biological microbiota variation in the infant gut could be explained. Our results highlight the need to interpret variance partitioning results in the context of each cohort's characteristics and microbiota processing.<br><br>INTERPRETATION: Our study provides a comprehensive report of key factors associated with infant gut microbiota composition across the two first years of life in a homogenous cohort. The study highlights possible important future research areas and confounding factors to be considered.<br><br>FUNDING: This research was supported by Business Finland, Academy of Finland, Foundation for Nutrition Research and the Doctoral Program in Microbiology and Biotechnology, University of Helsinki, Finland.}, }
@article {pmid37397017, year = {2023}, author = {You, Y and Yin, M and Zheng, X and Liang, Q and Zhang, H and Wu, BL and Xu, W}, title = {Saccharibacteria (TM7), but not other bacterial taxa, are associated with childhood caries regardless of age in a South China population.}, journal = {PeerJ}, volume = {11}, number = {}, pages = {e15605}, pmid = {37397017}, issn = {2167-8359}, mesh = {Child ; Humans ; Child, Preschool ; Male ; Female ; RNA, Ribosomal, 16S/genetics ; *Dental Caries/epidemiology ; Dental Caries Susceptibility ; Bacteria/genetics ; Firmicutes/genetics ; China/epidemiology ; }, abstract = {BACKGROUND: Human microbiome dysbiosis is related to various human diseases, and identifying robust and consistent biomarkers that apply in different populations is a key challenge. This challenge arises when identifying key microbial markers of childhood caries.<br><br>METHODS: We analyzed unstimulated saliva and supragingival plaque samples from children of different ages and sexes, performed 16S rRNA gene sequencing, and sought to identify whether consistent markers exist among subpopulations by using a multivariate linear regression model.<br><br>RESULTS: We found that Acinetobacter and Clostridiales bacterial taxa were associated with caries in plaque and saliva, respectively, while Firmicutes and Clostridia were found in plaque isolated from children of different ages in preschool and school. These identified bacterial markers largely differ between different populations, leaving only Saccharibacteria as a significant caries-associated phylum in children. Saccharibacteria is a newly identified phylum, and our taxonomic assignment database could not be used to identify its specific genus.<br><br>CONCLUSION: Our data indicated that, in a South China population, oral microbial signatures for dental caries show age and sex differences, but Saccharibacteria might be a consistent signal and worth further investigation, considering the lack of research on this microbe.}, }
@article {pmid37389570, year = {2023}, author = {Acosta, EM and Little, KA and Bratton, BP and Lopez, JG and Mao, X and Payne, AS and Donia, M and Devenport, D and Gitai, Z}, title = {Bacterial DNA on the skin surface overrepresents the viable skin microbiome.}, journal = {eLife}, volume = {12}, number = {}, pages = {}, pmid = {37389570}, issn = {2050-084X}, support = {P30 AR069589/AR/NIAMS NIH HHS/United States ; DP1 AI124669/AI/NIAID NIH HHS/United States ; TL1TR003019/TR/NCATS NIH HHS/United States ; TL1 TR003019/TR/NCATS NIH HHS/United States ; T32 GM007388/GM/NIGMS NIH HHS/United States ; GM007388/GM/NIGMS NIH HHS/United States ; }, mesh = {Humans ; Animals ; Mice ; DNA, Bacterial/genetics ; RNA, Ribosomal, 16S/genetics ; *Skin ; Aggression ; *Microbiota ; }, abstract = {The skin microbiome provides vital contributions to human health. However, the spatial organization and viability of its bacterial components remain unclear. Here, we apply culturing, imaging, and molecular approaches to human and mouse skin samples, and find that the skin surface is colonized by fewer viable bacteria than predicted by bacterial DNA levels. Instead, viable skin-associated bacteria are predominantly located in hair follicles and other cutaneous invaginations. Furthermore, we show that the skin microbiome has a uniquely low fraction of viable bacteria compared to other human microbiome sites, indicating that most bacterial DNA on the skin surface is not associated with viable cells Additionally, a small number of bacterial families dominate each skin site and traditional sequencing methods overestimate both the richness and diversity of the skin microbiome. Finally, we performed an in vivo skin microbiome perturbation-recovery study using human volunteers. Bacterial 16S rRNA gene sequencing revealed that, while the skin microbiome is remarkably stable even in the wake of aggressive perturbation, repopulation of the skin surface is driven by the underlying viable population. Our findings help explain the dynamics of skin microbiome perturbation as bacterial DNA on the skin surface can be transiently perturbed but is replenished by a stable underlying viable population. These results address multiple outstanding questions in skin microbiome biology with significant implications for future efforts to study and manipulate it.}, }
@article {pmid37389338, year = {2023}, author = {Loyola Irizarry, HG and Brito, IL}, title = {Characterizing conjugative plasmids from an antibiotic-resistant dataset for use as broad-host delivery vectors.}, journal = {Frontiers in microbiology}, volume = {14}, number = {}, pages = {1199640}, pmid = {37389338}, issn = {1664-302X}, abstract = {Human microbiome engineering is increasingly proposed as a way to modulate health outcomes. However, one of the current limitations to engineering microbial communities in situ is delivery of a genetic payload for introducing or modifying genes. Indeed, there is a need to identify novel broad-host delivery vectors for microbiome engineering. Therefore, in this study, we characterized conjugative plasmids from a publicly available dataset of antibiotic-resistant isolate genomes in order to identify potential broad-host vectors for further applications. From the 199 closed genomes available in the CDC &amp; FDA AR Isolate Bank, we identified 439 plasmids, of which 126 were predicted to be mobilizable and 206 conjugative. Various characteristics of the conjugative plasmids, such as size, replication origin, conjugation machinery, host defense mechanisms, and plasmid stability proteins, were analyzed to determine these plasmids' potential host-range. Following this analysis, we clustered plasmid sequences and chose 22 unique, broad-host range plasmids that would be suitable for use as delivery vectors. This novel set of plasmids will provide a valuable resource for engineering microbial communities.}, }
@article {pmid37389240, year = {2023}, author = {Efremova, I and Maslennikov, R and Poluektova, E and Vasilieva, E and Zharikov, Y and Suslov, A and Letyagina, Y and Kozlov, E and Levshina, A and Ivashkin, V}, title = {Epidemiology of small intestinal bacterial overgrowth.}, journal = {World journal of gastroenterology}, volume = {29}, number = {22}, pages = {3400-3421}, pmid = {37389240}, issn = {2219-2840}, mesh = {Humans ; *Diabetic Neuropathies ; Liver Cirrhosis ; Risk Factors ; Abdominal Pain ; Autonomic Nervous System ; }, abstract = {Small intestinal bacterial overgrowth (SIBO) is defined as an increase in the bacterial content of the small intestine above normal values. The presence of SIBO is detected in 33.8% of patients with gastroenterological complaints who underwent a breath test, and is significantly associated with smoking, bloating, abdominal pain, and anemia. Proton pump inhibitor therapy is a significant risk factor for SIBO. The risk of SIBO increases with age and does not depend on gender or race. SIBO complicates the course of a number of diseases and may be of pathogenetic significance in the development of their symptoms. SIBO is significantly associated with functional dyspepsia, irritable bowel syndrome, functional abdominal bloating, functional constipation, functional diarrhea, short bowel syndrome, chronic intestinal pseudo-obstruction, lactase deficiency, diverticular and celiac diseases, ulcerative colitis, Crohn's disease, cirrhosis, metabolic-associated fatty liver disease (MAFLD), primary biliary cholangitis, gastroparesis, pancreatitis, cystic fibrosis, gallstone disease, diabetes, hypothyroidism, hyperlipidemia, acromegaly, multiple sclerosis, autism, Parkinson's disease, systemic sclerosis, spondylarthropathy, fibromyalgia, asthma, heart failure, and other diseases. The development of SIBO is often associated with a slowdown in orocecal transit time that decreases the normal clearance of bacteria from the small intestine. The slowdown of this transit may be due to motor dysfunction of the intestine in diseases of the gut, autonomic diabetic polyneuropathy, and portal hypertension, or a decrease in the motor-stimulating influence of thyroid hormones. In a number of diseases, including cirrhosis, MAFLD, diabetes, and pancreatitis, an association was found between disease severity and the presence of SIBO. Further work on the effect of SIBO eradication on the condition and prognosis of patients with various diseases is required.}, }
@article {pmid37386089, year = {2023}, author = {Kadyan, S and Park, G and Wang, B and Singh, P and Arjmandi, B and Nagpal, R}, title = {Resistant starches from dietary pulses modulate the gut metabolome in association with microbiome in a humanized murine model of ageing.}, journal = {Scientific reports}, volume = {13}, number = {1}, pages = {10566}, pmid = {37386089}, issn = {2045-2322}, mesh = {Humans ; Animals ; Mice ; Aged ; Resistant Starch ; Disease Models, Animal ; Metabolome ; *Microbiota ; Diet, Western ; *Lens Plant ; Aging ; Bacteroidetes ; }, abstract = {Emerging evidence suggests that plant-based fiber-rich diets improve ageing-associated health by fostering a healthier gut microbiome and microbial metabolites. However, such effects and mechanisms of resistant starches from dietary pulses remain underexplored. Herein, we examine the prebiotic effects of dietary pulses-derived resistant starch (RS) on gut metabolome in older (60-week old) mice carrying a human microbiome. Gut metabolome and its association with microbiome are examined after 20-weeks feeding of a western-style diet (control; CTL) fortified (5% w/w) with RS from pinto beans (PTB), black-eyed-peas (BEP), lentils (LEN), chickpeas (CKP), or inulin (INU; reference control). NMR spectroscopy-based untargeted metabolomic analysis yield differential abundance linking phenotypic differences in specific metabolites among different RS groups. LEN and CKP increase butyrate, while INU promotes propionate. Conversely, bile acids and cholesterol are reduced in prebiotic groups along with suppressed choline-to-trimethylamine conversion by LEN and CKP, whereas amino acid metabolism is positively altered. Multi-omics microbiome-metabolome interactions reveal an association of beneficial metabolites with the Lactobacilli group, Bacteroides, Dubosiella, Parasutterella, and Parabacteroides, while harmful metabolites correlate with Butyricimonas, Faecalibaculum, Colidextribacter, Enterococcus, Akkermansia, Odoribacter, and Bilophila. These findings demonstrate the functional effects of pulses-derived RS on gut microbial metabolism and their beneficial physiologic responses in an aged host.}, }
@article {pmid37382539, year = {2023}, author = {Botin, T and Ramirez-Chamorro, L and Vidic, J and Langella, P and Martin-Verstraete, I and Chatel, JM and Auger, S}, title = {The Tolerance of Gut Commensal Faecalibacterium to Oxidative Stress Is Strain Dependent and Relies on Detoxifying Enzymes.}, journal = {Applied and environmental microbiology}, volume = {89}, number = {7}, pages = {e0060623}, pmid = {37382539}, issn = {1098-5336}, mesh = {Humans ; Reactive Oxygen Species/metabolism ; Faecalibacterium/metabolism ; *Hydrogen Peroxide/metabolism ; *Oxidative Stress ; Proteins/metabolism ; Bacteria/metabolism ; }, abstract = {Obligate anaerobic bacteria in genus Faecalibacterium are among the most dominant taxa in the colon of healthy individuals and contribute to intestinal homeostasis. A decline in the abundance of this genus is associated with the occurrence of various gastrointestinal disorders, including inflammatory bowel diseases. In the colon, these diseases are accompanied by an imbalance between the generation and elimination of reactive oxygen species (ROS), and oxidative stress is closely linked to disruptions in anaerobiosis. In this work, we explored the impact of oxidative stress on several strains of faecalibacteria. An in silico analysis of complete genomes of faecalibacteria revealed the presence of genes encoding O2- and/or ROS-detoxifying enzymes, including flavodiiron proteins, rubrerythrins, reverse rubrerythrins, superoxide reductases, and alkyl peroxidase. However, the presence and the number of these detoxification systems varied greatly among faecalibacteria. These results were confirmed by O2 stress survival tests, in which we found that strains differed widely in their sensitivity. We showed the protective role of cysteine, which limited the production of extracellular O2[•-] and improved the survival of Faecalibacterium longum L2-6 under high O2 tension. In the strain F. longum L2-6, we observed that the expression of genes encoding detoxifying enzymes was upregulated in the response to O2 or H2O2 stress but with different patterns of regulation. Based on these results, we propose a first model of the gene regulatory network involved in the response to oxidative stress in F. longum L2-6. IMPORTANCE Commensal bacteria in the genus Faecalibacterium have been proposed for use as next-generation probiotics, but efforts to cultivate and exploit the potential of these strains have been limited by their sensitivity to O2. More broadly, little is known about how commensal and health-associated bacterial species in the human microbiome respond to the oxidative stress that occurs as a result of inflammation in the colon. In this work, we provide insights regarding the genes that encode potential mechanisms of protection against O2 or ROS stress in faecalibacteria, which may facilitate future advances in work with these important bacteria.}, }
@article {pmid37379671, year = {2023}, author = {Steininger, H and Moltzau-Anderson, J and Lynch, SV}, title = {Contributions of the early-life microbiome to childhood atopy and asthma development.}, journal = {Seminars in immunology}, volume = {69}, number = {}, pages = {101795}, doi = {10.1016/j.smim.2023.101795}, pmid = {37379671}, issn = {1096-3618}, support = {UG3 OD023282/OD/NIH HHS/United States ; }, mesh = {Humans ; *Asthma ; *Hypersensitivity ; *Microbiota ; }, abstract = {The rapid rise in atopy and asthma in industrialized nations has led to the identification of early life environmental factors that promote these conditions and spurred research into how such exposures may mediate the trajectory to childhood disease development. Over the past decade, the human microbiome has emerged as a key determinant of human health. This is largely due to the increasing appreciation for the myriad of non-mutually exclusive mechanisms by which microbes tune and train host immunity. Microbiomes, particularly those in early life, are shaped by extrinsic and intrinsic factors, including many of the exposures known to influence allergy and asthma risk. This has led to the over-arching hypothesis that such exposures mediate their effect on childhood atopy and asthma by altering the functions and metabolic productivity of microbiomes that shape immune function during this critical developmental period. The capacity to study microbiomes at the genetic and molecular level in humans from the pre-natal period into childhood with well-defined clinical outcomes, offers an unprecedented opportunity to identify early-life and inter-generational determinants of atopy and asthma outcomes. Moreover, such studies provide an integrative microbiome research framework that can be applied to other chronic inflammatory conditions. This review attempts to capture key studies in the field that offer insights into the developmental origins of childhood atopy and asthma, providing novel insights into microbial mediators of maladaptive immunity and chronic inflammatory disease in childhood.}, }
@article {pmid37378284, year = {2023}, author = {Chmiel, JA and Carr, C and Stuivenberg, GA and Venema, R and Chanyi, RM and Al, KF and Giguere, D and Say, H and Akouris, PP and Domínguez Romero, SA and Kwong, A and Tai, V and Koval, SF and Razvi, H and Bjazevic, J and Burton, JP}, title = {Corrigendum: New perspectives on an old grouping: the genomic and phenotypic variability of Oxalobacter formigenes and the implications for calcium oxalate stone prevention.}, journal = {Frontiers in microbiology}, volume = {14}, number = {}, pages = {1231746}, pmid = {37378284}, issn = {1664-302X}, abstract = {[This corrects the article DOI: 10.3389/fmicb.2022.1011102.].}, }
@article {pmid37374978, year = {2023}, author = {Talapko, J and Meštrović, T and Dmitrović, B and Juzbašić, M and Matijević, T and Bekić, S and Erić, S and Flam, J and Belić, D and Petek Erić, A and Milostić Srb, A and Škrlec, I}, title = {A Putative Role of Candida albicans in Promoting Cancer Development: A Current State of Evidence and Proposed Mechanisms.}, journal = {Microorganisms}, volume = {11}, number = {6}, pages = {}, pmid = {37374978}, issn = {2076-2607}, abstract = {Candida albicans is a commensal fungal species that commonly colonizes the human body, but it is also a pervasive opportunistic pathogen in patients with malignant diseases. A growing body of evidence suggests that this fungus is not only coincidental in oncology patients, but may also play an active role in the development of cancer. More specifically, several studies have investigated the potential association between C. albicans and various types of cancer, including oral, esophageal, and colorectal cancer, with a possible role of this species in skin cancer as well. The proposed mechanisms include the production of carcinogenic metabolites, modulation of the immune response, changes in cell morphology, microbiome alterations, biofilm production, the activation of oncogenic signaling pathways, and the induction of chronic inflammation. These mechanisms may act together or independently to promote cancer development. Although more research is needed to fully grasp the potential role of C. albicans in carcinogenesis, the available evidence suggests that this species may be an active contributor and underscores the importance of considering the impact of the human microbiome on cancer pathogenesis. In this narrative review, we aimed to summarize the current state of evidence and offer some insights into proposed mechanisms.}, }
@article {pmid37373701, year = {2023}, author = {Villarejo-Campos, P and García-Arranz, M and Qian, S and Jiménez de Los Galanes, S and Domínguez-Prieto, V and Vélez-Pinto, JF and Guijo Castellano, I and Jiménez-Fuertes, M and Guadalajara, H and García-Olmo, D}, title = {Under the Hood: Understanding the Features of Mucin in Pseudomyxoma Peritonei.}, journal = {Journal of clinical medicine}, volume = {12}, number = {12}, pages = {}, pmid = {37373701}, issn = {2077-0383}, support = {PI20/01052 and DTS22/00048).//ISCIII-FEDER (Instituto de Salud Carlos III-Fondo Europeo de Desarrollo Regional), Spanish Ministry of Health/ ; }, abstract = {Pseudomyxoma peritonei (PMP) is a rare malignant growth characterized by the production of mucin and the potential for peritoneal relapse. This study aimed to investigate the immunohistochemical and biological characteristics of mucin in patients with cellular and acellular PMP. We prospectively analyzed mucin specimens obtained from our patient cohort and described the composition and type of mucin present in each sample. A metagenomic analysis of the samples was performed to investigate the bacterial composition of the PMP microbiome. Secreted mucins 2 and 5AC and membrane-associated mucin-1 were the primary components of mucin in both cellular and acellular tumor specimens. The metagenomic study revealed a predominance of the phylum Proteobacteria and the genus Pseudomonas. Notably, Pseudomonas plecoglossicida, a species not previously reported in the human microbiome, was found to be the most abundant organism in the mucin of pseudomyxoma peritonei. Our findings suggest that the presence of MUC-2 and mucin colonization by Pseudomonas are characteristic features of both cellular and acellular disease. These results may have significant implications for the diagnosis and treatment of this rare entity.}, }
@article {pmid37361341, year = {2023}, author = {Magill, RG and MacDonald, SM}, title = {Male infertility and the human microbiome.}, journal = {Frontiers in reproductive health}, volume = {5}, number = {}, pages = {1166201}, pmid = {37361341}, issn = {2673-3153}, abstract = {The historical belief in urology was that the genitourinary system should be sterile in a normal, healthy, asymptomatic adult. This idea was perpetuated for decades until research revealed a diverse microbiota existing in human anatomical niches that contributed to both human health and disease processes. In recent years, the search for an etiology and modifiable risk factors in infertility has turned to the human microbiome as well. Changes in the human gut microbiome have been associated with changes in systemic sex hormones and spermatogenesis. Certain microbial species are associated with higher levels of oxidative stress, which may contribute to an environment higher in oxidative reactive potential. Studies have demonstrated a link between increased oxidative reactive potential and abnormal semen parameters in infertile men. It has also been hypothesized that antioxidant probiotics may be able to correct an imbalance in the oxidative environment and improve male fertility, with promising results in small studies. Further, the sexual partner's microbiome may play a role as well; studies have demonstrated an overlap in the genitourinary microbiomes in sexually active couples that become more similar after intercourse. While the potential applications of the microbiome to male fertility is exciting, there is a need for larger studies with uniform microbial sequencing procedures to further expand this topic.}, }
@article {pmid37349675, year = {2023}, author = {Theorell, A and Stelling, J}, title = {Assumptions on decision making and environment can yield multiple steady states in microbial community models.}, journal = {BMC bioinformatics}, volume = {24}, number = {Suppl 1}, pages = {262}, pmid = {37349675}, issn = {1471-2105}, support = {177164//Schweizerischer Nationalfonds zur F&#xf6;rderung der Wissenschaftlichen Forschung/ ; }, mesh = {Humans ; *Models, Biological ; Computer Simulation ; *Microbiota ; Genome ; Decision Making ; }, abstract = {BACKGROUND: Microbial community simulations using genome scale metabolic networks (GSMs) are relevant for many application areas, such as the analysis of the human microbiome. Such simulations rely on assumptions about the culturing environment, affecting if the culture may reach a metabolically stationary state with constant microbial concentrations. They also require assumptions on decision making by the microbes: metabolic strategies can be in the interest of individual community members or of the whole community. However, the impact of such common assumptions on community simulation results has not been investigated systematically.<br><br>RESULTS: Here, we investigate four combinations of assumptions, elucidate how they are applied in literature, provide novel mathematical formulations for their simulation, and show how the resulting predictions differ qualitatively. Our results stress that different assumption combinations give qualitatively different predictions on microbial coexistence by differential substrate utilization. This fundamental mechanism is critically under explored in the steady state GSM literature with its strong focus on coexistence states due to crossfeeding (division of labor). Furthermore, investigating a realistic synthetic community, where the two involved strains exhibit no growth in isolation, but grow as a community, we predict multiple modes of cooperation, even without an explicit cooperation mechanism.<br><br>CONCLUSIONS: Steady state GSM modelling of microbial communities relies both on assumed decision making principles and environmental assumptions. In principle, dynamic flux balance analysis addresses both. In practice, our methods that address the steady state directly may be preferable, especially if the community is expected to display multiple steady states.}, }
@article {pmid37349525, year = {2023}, author = {Selma-Royo, M and Segata, N and Ricci, L}, title = {Human microbiome cultivation expands with AI.}, journal = {Nature biotechnology}, volume = {41}, number = {10}, pages = {1389-1391}, pmid = {37349525}, issn = {1546-1696}, mesh = {Humans ; *Microbiota ; Phylogeny ; }, }
@article {pmid37348522, year = {2023}, author = {Morton, SU and Hehnly, C and Burgoine, K and Ssentongo, P and Ericson, JE and Kumar, MS and Hagmann, C and Fronterre, C and Smith, J and Movassagh, M and Streck, N and Bebell, LM and Bazira, J and Kumbakumba, E and Bajunirwe, F and Mulondo, R and Mbabazi-Kabachelor, E and Nsubuga, BK and Natukwatsa, D and Nalule, E and Magombe, J and Erickson, T and Ngonzi, J and Ochora, M and Olupot-Olupot, P and Onen, J and Ssenyonga, P and Mugamba, J and Warf, BC and Kulkarni, AV and Lane, J and Whalen, AJ and Zhang, L and Sheldon, K and Meier, FA and Kiwanuka, J and Broach, JR and Paulson, JN and Schiff, SJ}, title = {Paenibacillus spp infection among infants with postinfectious hydrocephalus in Uganda: an observational case-control study.}, journal = {The Lancet. Microbe}, volume = {4}, number = {8}, pages = {e601-e611}, pmid = {37348522}, issn = {2666-5247}, support = {DP1 HD086071/HD/NICHD NIH HHS/United States ; R01 AI145057/AI/NIAID NIH HHS/United States ; }, mesh = {United States ; Infant, Newborn ; Child ; Humans ; Infant ; Female ; Pregnancy ; Uganda/epidemiology ; *Neonatal Sepsis/complications ; Placenta ; *Paenibacillus/genetics ; *Sepsis/complications/microbiology ; *Meningitis/complications ; *Hydrocephalus/epidemiology/etiology ; Case-Control Studies ; }, abstract = {BACKGROUND: Paenibacillus thiaminolyticus is a cause of postinfectious hydrocephalus among Ugandan infants. To determine whether Paenibacillus spp is a pathogen in neonatal sepsis, meningitis, and postinfectious hydrocephalus, we aimed to complete three separate studies of Ugandan infants. The first study was on peripartum prevalence of Paenibacillus in mother-newborn pairs. The second study assessed Paenibacillus in blood and cerebrospinal fluid (CSF) from neonates with sepsis. The third study assessed Paenibacillus in CSF from infants with hydrocephalus.<br><br>METHODS: In this observational study, we recruited mother-newborn pairs with and without maternal fever (mother-newborn cohort), neonates (aged &#x2264;28 days) with sepsis (sepsis cohort), and infants (aged &#x2264;90 days) with hydrocephalus with and without a history of neonatal sepsis and meningitis (hydrocephalus cohort) from three hospitals in Uganda between Jan 13, 2016 and Oct 2, 2019. We collected maternal blood, vaginal swabs, and placental samples and the cord from the mother-newborn pairs, and blood and CSF from neonates and infants. Bacterial content of infant CSF was characterised by 16S rDNA sequencing. We analysed all samples using quantitative PCR (qPCR) targeting either the Paenibacillus genus or Paenibacillus thiaminolyticus spp. We collected cranial ultrasound and computed tomography images in the subset of participants represented in more than one cohort.<br><br>FINDINGS: No Paenibacillus spp were detected in vaginal, maternal blood, placental, or cord blood specimens from the mother-newborn cohort by qPCR. Paenibacillus spp was detected in 6% (37 of 631 neonates) in the sepsis cohort and, of these, 14% (5 of 37 neonates) developed postinfectious hydrocephalus. Paenibacillus was the most enriched bacterial genera in postinfectious hydrocephalus CSF (91 [44%] of 209 patients) from the hydrocephalus cohort, with 16S showing 94% accuracy when validated by qPCR. Imaging showed progression from Paenibacillus spp-related meningitis to postinfectious hydrocephalus over 1-3 months. Patients with postinfectious hydrocephalus with Paenibacillus spp infections were geographically clustered.<br><br>INTERPRETATION: Paenibacillus spp causes neonatal sepsis and meningitis in Uganda and is the dominant cause of subsequent postinfectious hydrocephalus. There was no evidence of transplacental transmission, and geographical evidence was consistent with an environmental source of neonatal infection. Further work is needed to identify routes of infection and optimise treatment of neonatal Paenibacillus spp infection to lessen the burden of morbidity and mortality.<br><br>FUNDING: National Institutes of Health and Boston Children's Hospital Office of Faculty Development.}, }
@article {pmid37348505, year = {2023}, author = {Carter, MM and Olm, MR and Merrill, BD and Dahan, D and Tripathi, S and Spencer, SP and Yu, FB and Jain, S and Neff, N and Jha, AR and Sonnenburg, ED and Sonnenburg, JL}, title = {Ultra-deep sequencing of Hadza hunter-gatherers recovers vanishing gut microbes.}, journal = {Cell}, volume = {186}, number = {14}, pages = {3111-3124.e13}, pmid = {37348505}, issn = {1097-4172}, support = {DP1 AT009892/AT/NCCIH NIH HHS/United States ; F32 DK128865/DK/NIDDK NIH HHS/United States ; R01 DK085025/DK/NIDDK NIH HHS/United States ; T32 AI007328/AI/NIAID NIH HHS/United States ; T32 DK007056/DK/NIDDK NIH HHS/United States ; K08 DK134856/DK/NIDDK NIH HHS/United States ; }, mesh = {Humans ; *Gastrointestinal Microbiome/genetics ; *Microbiota ; Metagenome ; Eukaryota ; High-Throughput Nucleotide Sequencing ; Metagenomics ; }, abstract = {The gut microbiome modulates immune and metabolic health. Human microbiome data are biased toward industrialized populations, limiting our understanding of non-industrialized microbiomes. Here, we performed ultra-deep metagenomic sequencing on 351 fecal samples from the Hadza hunter-gatherers of Tanzania and comparative populations in Nepal and California. We recovered 91,662 genomes of bacteria, archaea, bacteriophages, and eukaryotes, 44% of which are absent from existing unified datasets. We identified 124 gut-resident species vanishing in industrialized populations and highlighted distinct aspects of the Hadza gut microbiome related to in situ replication rates, signatures of selection, and strain sharing. Industrialized gut microbes were found to be enriched in genes associated with oxidative stress, possibly a result of microbiome adaptation to inflammatory processes. This unparalleled view of the Hadza gut microbiome provides a valuable resource, expands our understanding of microbes capable of colonizing the human gut, and clarifies the extensive perturbation induced by the industrialized lifestyle.}, }
@article {pmid37345281, year = {2023}, author = {Launonen, H and Luiskari, L and Linden, J and Siltari, A and Salmenkari, H and Korpela, R and Vapaatalo, H}, title = {Adverse effects of an aldosterone synthase (CYP11B2) inhibitor, fadrozole (FAD286), on inflamed rat colon.}, journal = {Basic &amp; clinical pharmacology &amp; toxicology}, volume = {133}, number = {3}, pages = {211-225}, doi = {10.1111/bcpt.13918}, pmid = {37345281}, issn = {1742-7843}, support = {//Finska L&#xe4;kares&#xe4;llskapet/ ; //Mary and Georg C. Ehrnrooth's Foundation/ ; //Maud Kuistila Memory Foundation/ ; //Paulo Foundation/ ; //Finnish Cultural Foundation (Kymenlaakso regional fund, Olavi and Alli Pietik&#xe4;inen fund)/ ; }, mesh = {Rats ; Animals ; Mice ; *Cytochrome P-450 CYP11B2 ; *Fadrozole/toxicity ; Aldosterone ; Rats, Sprague-Dawley ; Iatrogenic Disease ; Inflammation/chemically induced ; Colon ; }, abstract = {Recently, we described local aldosterone production in the murine large intestine. Upregulated local aldosterone synthesis in different tissues has been linked with inflammatory conditions, which have been attenuated by the aldosterone synthase (CYP11B2) inhibitor, fadrozole (FAD286). Therefore, we investigated the effect of inhibition of intestinal aldosterone synthesis on the development of intestinal inflammation. Sprague-Dawley rats were administered 5% (v/w) dextran sodium sulphate (DSS) for 7 days with or without daily FAD286 (30 mg/kg/d) subcutaneous injections on 3 days before, during and one day after DSS. Tissue aldosterone concentrations were evaluated by ELISA, CYP11B2 by Western blot and RT-qPCR. FAD286 halved adrenal aldosterone production but, intriguingly, increased the colonic aldosterone concentration. The lack of inhibitory effect of FAD286 in the colon might have been affected by the smaller size of colonic vs. adrenal CYP11B2, as seen in Western blot. When combined with DSS, FAD286 aggravated the macroscopic and histological signs of intestinal inflammation, lowered the animals' body weight gain and increased the incidence of gastrointestinal bleeding and the permeability to iohexol in comparison to DSS-animals. To conclude, FAD286 exerted harmful effects during intestinal inflammation. Local intestinal aldosterone did not seem to play any role in the inflammatory pathogenesis occurring in the intestine.}, }
@article {pmid37343497, year = {2023}, author = {Ogilvie, CE and Czekster, CM}, title = {Cyclic dipeptides and the human microbiome: Opportunities and challenges.}, journal = {Bioorganic &amp; medicinal chemistry}, volume = {90}, number = {}, pages = {117372}, doi = {10.1016/j.bmc.2023.117372}, pmid = {37343497}, issn = {1464-3391}, support = {210486/Z/18/Z/WT_/Wellcome Trust/United Kingdom ; 204821/Z/16/Z/WT_/Wellcome Trust/United Kingdom ; }, mesh = {Humans ; *Dipeptides/pharmacology/chemistry ; Health Promotion ; *Microbiota ; }, abstract = {Research into the human microbiome has implicated its constituents in a variety of non-communicable diseases, with certain microbes found to promote health and others leading to dysbiosis and pathogenesis.Microbes communicate and coordinate their behaviour through the secretion of small molecules, such as cyclic dipeptides (CDPs), into their surrounding environment. CDPs are ubiquitous signalling molecules thatexhibit a wide range of biological activities, with particular relevance to human health due to their potential to act as microbiome modulators.}, }
@article {pmid37338299, year = {2023}, author = {Hurst, JH and Kelly, MS}, title = {Leveraging the human microbiota to target bacterial respiratory pathogens: new paths toward an expanded antimicrobial armamentarium.}, journal = {mBio}, volume = {14}, number = {4}, pages = {e0085423}, pmid = {37338299}, issn = {2150-7511}, support = {K01 AI173398/AI/NIAID NIH HHS/United States ; }, mesh = {Child ; Humans ; Moraxella catarrhalis/drug effects ; *Anti-Infective Agents ; *Respiratory Tract Infections/drug therapy/microbiology ; Anti-Bacterial Agents/pharmacology/therapeutic use ; }, abstract = {Acute respiratory infections are the most frequent infections across the lifespan and are the leading infectious cause of death among children globally. Bacterial respiratory infections are routinely treated with antibiotics, nearly all of which are derived from microbial natural products. Unfortunately, antibiotic-resistant bacteria are an increasingly frequent cause of respiratory infections, and there are few new antibiotics in development that target these pathogens. In the article by Stubbendieck et al., the authors identified Rothia species that demonstrate in vitro and ex vivo growth inhibition of the respiratory pathobiont Moraxella catarrhalis. The authors present experiments suggesting that this activity is mediated at least in part through the secretion of a novel peptidoglycan endopeptidase that targets the M. catarrhalis cell wall. In this commentary, we discuss these findings in the context of the urgent threat of antimicrobial resistance and highlight the promise of the human respiratory microbiota as a source of novel biotherapeutics.}, }
@article {pmid37333098, year = {2023}, author = {Grodner, B and Shi, H and Farchione, O and Vill, AC and Ntekas, I and Diebold, PJ and Zipfel, WR and Brito, IL and Vlaminck, I}, title = {Spatial Mapping of Mobile Genetic Elements and their Cognate Hosts in Complex Microbiomes.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {37333098}, issn = {2692-8205}, support = {DP2 AI138242/AI/NIAID NIH HHS/United States ; R33 CA235302/CA/NCI NIH HHS/United States ; S10 OD018516/OD/NIH HHS/United States ; }, abstract = {The frequent exchange of mobile genetic elements (MGEs) between bacteria accelerates the spread of functional traits, including antimicrobial resistance, within the human microbiome. Yet, progress in understanding these intricate processes has been hindered by the lack of tools to map the spatial spread of MGEs in complex microbial communities, and to associate MGEs to their bacterial hosts. To overcome this challenge, we present an imaging approach that pairs single molecule DNA Fluorescence In Situ Hybridization (FISH) with multiplexed ribosomal RNA FISH, thereby enabling the simultaneous visualization of both MGEs and host bacterial taxa. We used this methodology to spatially map bacteriophage and antimicrobial resistance (AMR) plasmids in human oral biofilms, and we studied the heterogeneity in their spatial distributions and demonstrated the ability to identify their host taxa. Our data revealed distinct clusters of both AMR plasmids and prophage, coinciding with densely packed regions of host bacteria in the biofilm. These results suggest the existence of specialized niches that maintain MGEs within the community, possibly acting as local hotspots for horizontal gene transfer. The methods introduced here can help advance the study of MGE ecology and address pressing questions regarding antimicrobial resistance and phage therapy.}, }
@article {pmid37331612, year = {2023}, author = {Adelfio, M and Bonzanni, M and Callen, GE and Paster, BJ and Hasturk, H and Ghezzi, CE}, title = {A physiologically relevant culture platform for long-term studies of in vitro gingival tissue.}, journal = {Acta biomaterialia}, volume = {167}, number = {}, pages = {321-334}, pmid = {37331612}, issn = {1878-7568}, support = {R03 DE030224/DE/NIDCR NIH HHS/United States ; }, mesh = {Humans ; *Gingiva/pathology ; *Periodontitis/microbiology/pathology ; Epithelium ; Bacteria ; Biomarkers ; Porphyromonas gingivalis ; }, abstract = {There is a clinical need to understand the etiologies of periodontitis, considering the growing socio-economic impact of the disease. Despite recent advances in oral tissue engineering, experimental approaches have failed to develop a physiologically relevant gingival model that combines tissue organization with salivary flow dynamics and stimulation of the shedding and non-shedding oral surfaces. Herein, we develop a dynamic gingival tissue model composed of a silk scaffold, replicating the cyto-architecture and oxygen profile of the human gingiva, along with a saliva-mimicking medium that reflected the ionic composition, viscosity, and non-Newtonian behavior of human saliva. The construct was cultured in a custom designed bioreactor, in which force profiles on the gingival epithelium were modulated through analysis of inlet position, velocity and vorticity to replicate the physiological shear stress of salivary flow. The gingival bioreactor supported the long-term in vivo features of the gingiva and improved the integrity of the epithelial barrier, critical against the invasion of pathogenic bacteria. Furthermore, the challenge of the gingival tissue with P. gingivalis lipopolysaccharide, as an in vitro surrogate for microbial interactions, indicated a greater stability of the dynamic model in maintaining tissue homeostasis and, thus, its applicability in long-term studies. The model will be integrated into future studies with the human subgingival microbiome to investigate host-pathogen and host-commensal interactions. STATEMENT OF SIGNIFICANCE: The major societal impact of human microbiome had reverberated up to the establishment of the Common Fund's Human Microbiome Project, that has the intent of studying the role of microbial communities in human health and diseases, including periodontitis, atopic dermatitis, or asthma and inflammatory bowel disease. In addition, these chronic diseases are emergent drivers of global socioeconomic status. Not only common oral diseases have been shown to be directly correlated with several systemic conditions, but they are differentially impacting some racial/ethnic and socioeconomic groups. To address this growing social disparity, the development of in vitro gingival model would provide a time and cost-effective experimental platform, able to mimic the spectrum of periodontal disease presentation, for the identification of predictive biomarkers for early-stage diagnosis.}, }
@article {pmid37330560, year = {2023}, author = {Algavi, YM and Borenstein, E}, title = {A data-driven approach for predicting the impact of drugs on the human microbiome.}, journal = {Nature communications}, volume = {14}, number = {1}, pages = {3614}, pmid = {37330560}, issn = {2041-1723}, support = {U19 AG057377/AG/NIA NIH HHS/United States ; }, mesh = {Animals ; Humans ; *Microbiota ; *Gastrointestinal Microbiome ; *Drug-Related Side Effects and Adverse Reactions ; Genomics ; Dysbiosis ; }, abstract = {Many medications can negatively impact the bacteria residing in our gut, depleting beneficial species, and causing adverse effects. To guide personalized pharmaceutical treatment, a comprehensive understanding of the impact of various drugs on the gut microbiome is needed, yet, to date, experimentally challenging to obtain. Towards this end, we develop a data-driven approach, integrating information about the chemical properties of each drug and the genomic content of each microbe, to systematically predict drug-microbiome interactions. We show that this framework successfully predicts outcomes of in-vitro pairwise drug-microbe experiments, as well as drug-induced microbiome dysbiosis in both animal models and clinical trials. Applying this methodology, we systematically map a large array of interactions between pharmaceuticals and human gut bacteria and demonstrate that medications' anti-microbial properties are tightly linked to their adverse effects. This computational framework has the potential to unlock the development of personalized medicine and microbiome-based therapeutic approaches, improving outcomes and minimizing side effects.}, }
@article {pmid37328672, year = {2023}, author = {O'Toole, PW and Paoli, M}, title = {The human microbiome, global health and the Sustainable Development Goals: opportunities and challenges.}, journal = {Nature reviews. Microbiology}, volume = {21}, number = {10}, pages = {624-625}, pmid = {37328672}, issn = {1740-1534}, mesh = {Humans ; *Global Health ; Sustainable Development ; Public Health ; *Microbiota ; }, }
@article {pmid37328513, year = {2023}, author = {Del Chierico, F and Marzano, V and Scanu, M and Reddel, S and Dentici, ML and Capolino, R and Di Donato, M and Spasari, I and Fiscarelli, EV and Digilio, MC and Abreu, MT and Dallapiccola, B and Putignani, L}, title = {Analysis of gut microbiota in patients with Williams-Beuren Syndrome reveals dysbiosis linked to clinical manifestations.}, journal = {Scientific reports}, volume = {13}, number = {1}, pages = {9797}, pmid = {37328513}, issn = {2045-2322}, mesh = {Humans ; *Williams Syndrome/genetics/diagnosis ; Dysbiosis/microbiology ; *Gastrointestinal Microbiome ; RNA, Ribosomal, 16S/genetics ; Quality of Life ; *Gastrointestinal Diseases/complications ; }, abstract = {Williams-Beuren syndrome (WBS) is a multisystem genetic disease caused by the deletion of a region of 1.5-1.8 Mb on chromosome 7q11.23. The elastin gene seems to account for several comorbidities and distinct clinical features such including cardiovascular disease, connective tissue abnormalities, growth retardation, and gastrointestinal (GI) symptoms. Increasing evidence points to alterations in gut microbiota composition as a primary or secondary cause of some GI or extra-intestinal characteristics. In this study, we performed the first exploratory analysis of gut microbiota in WBS patients compared to healthy subjects (CTRLs) using 16S rRNA amplicon sequencing, by investigating the gut dysbiosis in relation to diseases and comorbidities. We found that patients with WBS have significant dysbiosis compared to age-matched CTRLs, characterized by an increase in proinflammatory bacteria such as Pseudomonas, Gluconacetobacter and Eggerthella, and a reduction of anti-inflammatory bacteria including Akkermansia and Bifidobacterium. Microbial biomarkers associated with weight gain, GI symptoms and hypertension were identified. Gut microbiota profiling could represent a new tool that characterise intestinal dysbiosis to complement the clinical management of these patients. In particular, the administration of microbial-based treatments, alongside traditional therapies, could help in reducing or preventing the burden of these symptoms and improve the quality of life of these patients.}, }
@article {pmid37325707, year = {2023}, author = {Wang, Y and Zhang, R and Pu, Y and Wang, D and Wang, Y and Wu, X and Pan, Y and Luo, C and Zhao, G and Quan, Z and Zheng, Y}, title = {Sample Collection, DNA Extraction, and Library Construction Protocols of the Human Microbiome Studies in the International Human Phenome Project.}, journal = {Phenomics (Cham, Switzerland)}, volume = {3}, number = {3}, pages = {300-308}, pmid = {37325707}, issn = {2730-5848}, abstract = {UNLABELLED: The human microbiome plays a crucial role in human health. In the past decade, advances in high-throughput sequencing technologies and analytical software have significantly improved our knowledge of the human microbiome. However, most studies concerning the human microbiome did not provide repeatable protocols to guide the sample collection, handling, and processing procedures, which impedes obtaining valid and timely microbial taxonomic and functional results. This protocol provides detailed operation methods of human microbial sample collection, DNA extraction, and library construction for both the amplicon sequencing-based measurements of the microbial samples from the human nasal cavity, oral cavity, and skin, as well as the shotgun metagenomic sequencing-based measurements of the human stool samples among adult participants. This study intends to develop practical procedure standards to improve the reproducibility of microbiota profiling of human samples.<br><br>SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s43657-023-00097-y.}, }
@article {pmid37324782, year = {2023}, author = {Campbell, CD and Gleeson, M and Sulaiman, I}, title = {The role of the respiratory microbiome in asthma.}, journal = {Frontiers in allergy}, volume = {4}, number = {}, pages = {1120999}, pmid = {37324782}, issn = {2673-6101}, abstract = {Asthma is a common airways disease and the human microbiome plays an increasingly recognised role in asthma pathogenesis. Furthermore, the respiratory microbiome varies with asthma phenotype, endotype and disease severity. Consequently, asthma therapies have a direct effect on the respiratory microbiome. Newer biological therapies have led to a significant paradigm shift in how we treat refractory Type 2 high asthma. While airway inflammation is the generally accepted mechanism of action of all asthma therapies, including both inhaled and systemic therapies, there is evidence to suggest that they may also alter the microbiome to create a more functionally balanced airway microenvironment while also influencing airway inflammation directly. This downregulated inflammatory cascade seen biochemically, and reflected in improved clinical outcomes, supports the hypothesis that biological therapies may in fact affect the microbiome-host immune system dynamic and thus represent a therapeutic target for exacerbations and disease control.}, }
@article {pmid37323911, year = {2023}, author = {Nowicki, C and Ray, L and Engen, P and Madrigrano, A and Witt, T and Lad, T and Cobleigh, M and Mutlu, EA}, title = {Comparison of gut microbiome composition in colonic biopsies, endoscopically-collected and at-home-collected stool samples.}, journal = {Frontiers in microbiology}, volume = {14}, number = {}, pages = {1148097}, pmid = {37323911}, issn = {1664-302X}, abstract = {AIM: The goal of this study is to compare microbiome composition in three different sample types in women, namely stool brought from home vs. solid stool samples obtained at the time of an unprepped sigmoidoscopy vs. biopsies of the colonic mucosa at the time of an unprepped sigmoidoscopy, using alpha- and beta-diversity metrics following bacterial 16S rRNA sequencing. The findings may have relevance to health and disease states in which bacterial metabolism has a significant impact on molecules/metabolites that are recirculated between the gut lumen and mucosa and systemic circulation, such as estrogens (as in breast cancer) or bile acids.<br><br>METHODS: Concomitant at-home-collected stool, endoscopically-collected stool, and colonic biopsy samples were collected from 48 subjects (24 breast cancer, 24 control.) After 16S rRNA sequencing, an amplicon sequence variant (ASV) based approach was used to analyze the data. Alpha diversity metrics (Chao1, Pielou's Evenness, Faith PD, Shannon, and Simpson) and beta diversity metrics (Bray-Curtis, Weighted and Unweighted Unifrac) were calculated. LEfSe was used to analyze differences in the abundance of various taxa between sample types.<br><br>RESULTS: Alpha and beta diversity metrics were significantly different between the three sample types. Biopsy samples were different than stool samples in all metrics. The highest variation in microbiome diversity was noted in the colonic biopsy samples. At-home and endoscopically-collected stool showed more similarities in count-based and weighted beta diversity metrics. There were significant differences in rare taxa and phylogenetically-diverse taxa between the two types of stool samples. Generally, there were higher levels of Proteobacteria in biopsy samples, with significantly more Actinobacteria and Firmicutes in stool (all p <&#x2009;0.001, q-value < 0.05). Overall, there was a significantly higher relative abundance of Lachnospiraceae and Ruminococcaceae in stool samples (at-home collected and endoscopically-collected) and higher abundances of Tisserellaceae in biopsy samples (all p <&#x2009;0.001, q-value < 0.05).<br><br>CONCLUSION: Our data shows that different sampling methods can impact results when looking at the composition of the gut microbiome using ASV-based approaches.}, }
@article {pmid37321219, year = {2023}, author = {Chen, H and Rosen, CE and González-Hernández, JA and Song, D and Potempa, J and Ring, AM and Palm, NW}, title = {Highly multiplexed bioactivity screening reveals human and microbiota metabolome-GPCRome interactions.}, journal = {Cell}, volume = {186}, number = {14}, pages = {3095-3110.e19}, pmid = {37321219}, issn = {1097-4172}, support = {R21 AI137935/AI/NIAID NIH HHS/United States ; R01 DE030939/DE/NIDCR NIH HHS/United States ; UL1 TR001863/TR/NCATS NIH HHS/United States ; RM1 GM141649/GM/NIGMS NIH HHS/United States ; DP2 DK125119/DK/NIDDK NIH HHS/United States ; R01 DE022597/DE/NIDCR NIH HHS/United States ; R01 AG068863/AG/NIA NIH HHS/United States ; K22 AI123477/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Humans ; *Receptors, G-Protein-Coupled/metabolism ; *Microbiota ; Metabolome ; Mammals/metabolism ; }, abstract = {The human body contains thousands of metabolites derived from mammalian cells, the microbiota, food, and medical drugs. Many bioactive metabolites act through the engagement of G-protein-coupled receptors (GPCRs); however, technological limitations constrain current explorations of metabolite-GPCR interactions. Here, we developed a highly multiplexed screening technology called PRESTO-Salsa that enables simultaneous assessment of nearly all conventional GPCRs (>300 receptors) in a single well of a 96-well plate. Using PRESTO-Salsa, we screened 1,041 human-associated metabolites against the GPCRome and uncovered previously unreported endogenous, exogenous, and microbial GPCR agonists. Next, we leveraged PRESTO-Salsa to generate an atlas of microbiome-GPCR interactions across 435 human microbiome strains from multiple body sites, revealing conserved patterns of cross-tissue GPCR engagement and activation of CD97/ADGRE5 by the Porphyromonas gingivalis protease gingipain K. These studies thus establish a highly multiplexed bioactivity screening technology and expose a diverse landscape of human, diet, drug, and microbiota metabolome-GPCRome interactions.}, }
@article {pmid37320892, year = {2023}, author = {Santosh Kumar, BY and Mohan Kumar, GC and Shahapurkar, K and Tirth, V and Algahtani, A and Al-Mughanam, T and Alghtani, AH and Ananda Murthy, HC}, title = {Processing and characterization of egg shell derived nano-hydroxyapatite synthetic bone for Orthopaedic and Arthroscopy implants and substitutes in dentistry.}, journal = {Journal of the mechanical behavior of biomedical materials}, volume = {144}, number = {}, pages = {105963}, doi = {10.1016/j.jmbbm.2023.105963}, pmid = {37320892}, issn = {1878-0180}, mesh = {Animals ; Humans ; *Durapatite/chemistry ; Egg Shell ; *Orthopedics ; Arthroscopy ; Bone and Bones ; Tissue Engineering/methods ; X-Ray Diffraction ; Dentistry ; Spectroscopy, Fourier Transform Infrared ; Tissue Scaffolds/chemistry ; }, abstract = {The present work is focused on the nano-Hydroxyapatite (nHAp) synthesis with two different Indian breed Aseel and Kadaknath eggshells. The alloplast implants were developed through the foam replica method with polyurethane 45-PPI as a porous template. The synthesized nHAp was characterized by Field Emission Scanning Electron Microscopy (FE-SEM), X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FTIR). The FE-SEM images of the nHAp showed the one dimensional clustered nanoparticles and the X-ray diffraction spectrum confirms that the major phase was hydroxyapatite with a small trace of β-tricalcium phosphate. The maximum compression strength of the sample was 5.49 ± 0.12 MPa which is in the range of the compression strength of human trabecular bone. The thermal and degradability studies results confirmed that these are highly stable and provides necessary a resorption needed for new bone tissue formation. Besides, the antimicrobial activity against tested human microbiome are satisfactory and the cell viability towards MG 63 human osteoblast-like cells provides a potential pathway for developing the nHAp implants for bone tissue engineering.}, }
@article {pmid37317139, year = {2023}, author = {Clarke, TH and Greco, C and Brinkac, L and Nelson, KE and Singh, H}, title = {MPrESS: An R-Package for Accurately Predicting Power for Comparisons of 16S rRNA Microbiome Taxa Distributions including Simulation by Dirichlet Mixture Modeling.}, journal = {Microorganisms}, volume = {11}, number = {5}, pages = {}, pmid = {37317139}, issn = {2076-2607}, support = {2015-R2-CX-K036//National Institute of Justice/ ; }, abstract = {Deep sequencing has revealed that the 16S rRNA gene composition of the human microbiome can vary between populations. However, when existing data are insufficient to address the desired study questions due to limited sample sizes, Dirichlet mixture modeling (DMM) can simulate 16S rRNA gene predictions from experimental microbiome data. We examined the extent to which simulated 16S rRNA gene microbiome data can accurately reflect the diversity within that identified from experimental data and calculate the power. Even when experimental and simulated datasets differed by less than 10%, simulation by DMM consistently overestimates power, except when using only highly discriminating taxa. Admixtures of DMM with experimental data performed poorly compared to pure simulation and did not show the same correlation with experimental data p-value and power values. While multiple replications of random sampling remain the favored method of determining the power, when the estimated sample size required to achieve a certain power exceeds the sample number, then simulated samples based on DMM can be used. We introduce an R-Package, MPrESS, to assist in power calculation and sample size estimation for a 16S rRNA gene microbiome dataset to detect a difference between populations. MPrESS can be downloaded from GitHub.}, }
@article {pmid37317128, year = {2023}, author = {Bar, K and Litera-Bar, M and Sozańska, B}, title = {Bacterial Microbiota of Asthmatic Children and Preschool Wheezers' Airways-What Do We Know?.}, journal = {Microorganisms}, volume = {11}, number = {5}, pages = {}, pmid = {37317128}, issn = {2076-2607}, abstract = {Asthma is the most chronic pulmonary disease in pediatric population, and its etiopathology still remains unclear. Both viruses and bacteria are suspected factors of disease development and are responsible for its exacerbation. Since the launch of The Human Microbiome Project, there has been an explosion of research on microbiota and its connection with various diseases. In our review, we have collected recent data about both upper- and lower-airway bacterial microbiota of asthmatic children. We have also included studies regarding preschool wheezers, since asthma diagnosis in children under 5 years of age remains challenging due to the lack of an objective tool. This paper indicates the need for further studies of microbiome and asthma, as in today's knowledge, there is no particular bacterium that discriminates the asthmatics from the healthy peers and can be used as a potential biological factor in the disease prevalence and treatment.}, }
@article {pmid37312410, year = {2023}, author = {Liu, C and Gong, J and Zhang, Q and Chen, G and Yin, S and Luo, Z and Zeng, W and Yu, J and Lan, P and He, Z}, title = {Dietary iron modulates gut microbiota and induces SLPI secretion to promote colorectal tumorigenesis.}, journal = {Gut microbes}, volume = {15}, number = {1}, pages = {2221978}, pmid = {37312410}, issn = {1949-0984}, mesh = {Animals ; Mice ; *Gastrointestinal Microbiome ; Iron, Dietary ; Secretory Leukocyte Peptidase Inhibitor ; Carcinogenesis ; Iron ; *Colorectal Neoplasms ; }, abstract = {Dietary iron intake is closely related to the incidence of colorectal cancer. However, the interactions among dietary iron, gut microbiota, and epithelial cells in promoting tumorigenesis have rarely been discussed. Here, we report that gut microbiota plays a crucial role in promoting colorectal tumorigenesis in multiple mice models under excessive dietary iron intake. Gut microbiota modulated by excessive dietary iron are pathogenic, irritating the permeability of the gut barrier and causing leakage of lumen bacteria. Mechanistically, epithelial cells released more secretory leukocyte protease inhibitor (SLPI) to combat the leaked bacteria and limit inflammation. The upregulated SLPI acted as a pro-tumorigenic factor and promoted colorectal tumorigenesis by activating the MAPK signaling pathway. Moreover, excessive dietary iron significantly depleted Akkermansiaceae in the gut microbiota; while supplementation with Akkermansia muciniphila could successfully attenuate the tumorigenic effect from excessive dietary iron. Overall, excessive dietary iron perturbs diet - microbiome-epithelium interactions, which contributes to intestinal tumor initiation.}, }
@article {pmid37310633, year = {2023}, author = {Shin, W and Kim, HJ}, title = {In Vitro Morphogenesis and Differentiation of Human Intestinal Epithelium in a Gut-on-a-Chip.}, journal = {Methods in molecular biology (Clifton, N.J.)}, volume = {2650}, number = {}, pages = {197-206}, pmid = {37310633}, issn = {1940-6029}, support = {K00 CA245801/CA/NCI NIH HHS/United States ; R21 CA236690/CA/NCI NIH HHS/United States ; }, mesh = {Humans ; Caco-2 Cells ; *Intestinal Mucosa ; Cell Differentiation ; Morphogenesis ; *Lab-On-A-Chip Devices ; }, abstract = {The establishment of a three-dimensional (3D) epithelial structure and cytodifferentiation in vitro is necessary to recapitulate in vivo-relevant structure and function of the human intestine. Here, we describe an experimental protocol to build an organomimetic gut-on-a-chip microdevice that allows inducing 3D morphogenesis of human intestinal epithelium using Caco-2 cells or intestinal organoid cells. Under physiological flow and physical motions, intestinal epithelium spontaneously recreates 3D epithelial morphology in a gut-on-a-chip that offers enhanced mucus production, epithelial barrier, and longitudinal host-microbe co-culture. This protocol may provide implementable strategies to advance traditional in vitro static cultures, human microbiome studies, and pharmacological testing.}, }
@article {pmid37305030, year = {2023}, author = {Wang, Y and Salonen, A and Jian, C}, title = {Can prebiotics help tackle the childhood obesity epidemic?.}, journal = {Frontiers in endocrinology}, volume = {14}, number = {}, pages = {1178155}, pmid = {37305030}, issn = {1664-2392}, mesh = {Child ; Adolescent ; Adult ; Humans ; *Pediatric Obesity/epidemiology/prevention &amp; control ; Prebiotics ; Overweight ; Adiposity ; Dysbiosis/epidemiology/prevention &amp; control ; }, abstract = {Globally, excess weight during childhood and adolescence has become a public health crisis with limited treatment options. Emerging evidence suggesting the involvement of gut microbial dysbiosis in obesity instills hope that targeting the gut microbiota could help prevent or treat obesity. In pre-clinical models and adults, prebiotic consumption has been shown to reduce adiposity partially via restoring symbiosis. However, there is a dearth of clinical research into its potential metabolic benefits in the pediatric population. Here, we provide a succinct overview of the common characteristics of the gut microbiota in childhood obesity and mechanisms of action of prebiotics conferring metabolic benefits. We then summarize available clinical trials in children with overweight or obesity investigating the effects of prebiotics on weight management. This review highlights several controversial aspects in the microbiota-dependent mechanisms by which prebiotics are thought to affect host metabolism that warrant future investigation in order to design efficacious interventions for pediatric obesity.}, }
@article {pmid37301875, year = {2023}, author = {Li, L and Wang, T and Ning, Z and Zhang, X and Butcher, J and Serrana, JM and Simopoulos, CMA and Mayne, J and Stintzi, A and Mack, DR and Liu, YY and Figeys, D}, title = {Revealing proteome-level functional redundancy in the human gut microbiome using ultra-deep metaproteomics.}, journal = {Nature communications}, volume = {14}, number = {1}, pages = {3428}, pmid = {37301875}, issn = {2041-1723}, support = {U19 AI095219/AI/NIAID NIH HHS/United States ; U01 HL089856/HL/NHLBI NIH HHS/United States ; RF1 AG067744/AG/NIA NIH HHS/United States ; R01 AI141529/AI/NIAID NIH HHS/United States ; R01 HD093761/HD/NICHD NIH HHS/United States ; UH3 OD023268/OD/NIH HHS/United States ; }, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; Proteome ; Proteomics ; Xenobiotics ; Feces ; *Microbiota ; }, abstract = {Functional redundancy is a key ecosystem property representing the fact that different taxa contribute to an ecosystem in similar ways through the expression of redundant functions. The redundancy of potential functions (or genome-level functional redundancy [Formula: see text]) of human microbiomes has been recently quantified using metagenomics data. Yet, the redundancy of expressed functions in the human microbiome has never been quantitatively explored. Here, we present an approach to quantify the proteome-level functional redundancy [Formula: see text] in the human gut microbiome using metaproteomics. Ultra-deep metaproteomics reveals high proteome-level functional redundancy and high nestedness in the human gut proteomic content networks (i.e., the bipartite graphs connecting taxa to functions). We find that the nested topology of proteomic content networks and relatively small functional distances between proteomes of certain pairs of taxa together contribute to high [Formula: see text] in the human gut microbiome. As a metric comprehensively incorporating the factors of presence/absence of each function, protein abundances of each function and biomass of each taxon, [Formula: see text] outcompetes diversity indices in detecting significant microbiome responses to environmental factors, including individuality, biogeography, xenobiotics, and disease. We show that gut inflammation and exposure to specific xenobiotics can significantly diminish the [Formula: see text] with no significant change in taxonomic diversity.}, }
@article {pmid37301199, year = {2023}, author = {Stražar, M and Park, J and Abelin, JG and Taylor, HB and Pedersen, TK and Plichta, DR and Brown, EM and Eraslan, B and Hung, YM and Ortiz, K and Clauser, KR and Carr, SA and Xavier, RJ and Graham, DB}, title = {HLA-II immunopeptidome profiling and deep learning reveal features of antigenicity to inform antigen discovery.}, journal = {Immunity}, volume = {56}, number = {7}, pages = {1681-1698.e13}, pmid = {37301199}, issn = {1097-4180}, support = {U19 AI110495/AI/NIAID NIH HHS/United States ; P30 DK043351/DK/NIDDK NIH HHS/United States ; RC2 DK114784/DK/NIDDK NIH HHS/United States ; U24 CA271075/CA/NCI NIH HHS/United States ; U24 CA270823/CA/NCI NIH HHS/United States ; P01 CA206978/CA/NCI NIH HHS/United States ; U24 CA210979/CA/NCI NIH HHS/United States ; }, mesh = {Humans ; Captan ; *Deep Learning ; *COVID-19 ; SARS-CoV-2 ; HLA Antigens ; Epitopes, T-Lymphocyte ; Peptides ; }, abstract = {CD4+ T cell responses are exquisitely antigen specific and directed toward peptide epitopes displayed by human leukocyte antigen class II (HLA-II) on antigen-presenting cells. Underrepresentation of diverse alleles in ligand databases and an incomplete understanding of factors affecting antigen presentation in vivo have limited progress in defining principles of peptide immunogenicity. Here, we employed monoallelic immunopeptidomics to identify 358,024 HLA-II binders, with a particular focus on HLA-DQ and HLA-DP. We uncovered peptide-binding patterns across a spectrum of binding affinities and enrichment of structural antigen features. These aspects underpinned the development of context-aware predictor of T cell antigens (CAPTAn), a deep learning model that predicts peptide antigens based on their affinity to HLA-II and full sequence of their source proteins. CAPTAn was instrumental in discovering prevalent T cell epitopes from bacteria in the human microbiome and a pan-variant epitope from SARS-CoV-2. Together CAPTAn and associated datasets present a resource for antigen discovery and the unraveling genetic associations of HLA alleles with immunopathologies.}, }
@article {pmid37299414, year = {2023}, author = {Hughes, RL and Frankenfeld, CL and Gohl, DM and Huttenhower, C and Jackson, SA and Vandeputte, D and Vogtmann, E and Comstock, SS and Kable, ME}, title = {Methods in Nutrition &amp; Gut Microbiome Research: An American Society for Nutrition Satellite Session [13 October 2022].}, journal = {Nutrients}, volume = {15}, number = {11}, pages = {}, pmid = {37299414}, issn = {2072-6643}, support = {IAFNS-HUGESRILEY-20221026//Institute for the Advancement of Food and Nutrition Sciences/ ; }, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; Nutritional Status ; *Microbiota ; Research ; *Nutrition Therapy ; }, abstract = {The microbial cells colonizing the human body form an ecosystem that is integral to the regulation and maintenance of human health. Elucidation of specific associations between the human microbiome and health outcomes is facilitating the development of microbiome-targeted recommendations and treatments (e.g., fecal microbiota transplant; pre-, pro-, and post-biotics) to help prevent and treat disease. However, the potential of such recommendations and treatments to improve human health has yet to be fully realized. Technological advances have led to the development and proliferation of a wide range of tools and methods to collect, store, sequence, and analyze microbiome samples. However, differences in methodology at each step in these analytic processes can lead to variability in results due to the unique biases and limitations of each component. This technical variability hampers the detection and validation of associations with small to medium effect sizes. Therefore, the American Society for Nutrition (ASN) Nutritional Microbiology Group Engaging Members (GEM), sponsored by the Institute for the Advancement of Food and Nutrition Sciences (IAFNS), hosted a satellite session on methods in nutrition and gut microbiome research to review currently available methods for microbiome research, best practices, as well as tools and standards to aid in comparability of methods and results. This manuscript summarizes the topics and research discussed at the session. Consideration of the guidelines and principles reviewed in this session will increase the accuracy, precision, and comparability of microbiome research and ultimately the understanding of the associations between the human microbiome and health.}, }
@article {pmid37299395, year = {2023}, author = {Policastro, V and Righelli, D and Ravà, L and Vernocchi, P and Bianchi, M and Vallone, C and Signore, F and Manco, M}, title = {Dietary Fatty Acids Contribute to Maintaining the Balance between Pro-Inflammatory and Anti-Inflammatory Responses during Pregnancy.}, journal = {Nutrients}, volume = {15}, number = {11}, pages = {}, pmid = {37299395}, issn = {2072-6643}, support = {GR-2010-2304957//Ministero della Salute/ ; }, mesh = {Female ; Humans ; Pregnancy ; *Leptin ; Intercellular Adhesion Molecule-1 ; *Diabetes, Gestational ; Adiponectin ; Fatty Acids ; Cytokines ; }, abstract = {BACKGROUND: During pregnancy, the balance between pro-inflammatory and anti-inflammatory responses is essential for ensuring healthy outcomes. Dietary Fatty acids may modulate inflammation.<br><br>METHODS: We investigated the association between dietary fatty acids as profiled on red blood cells membranes and a few pro- and anti-inflammatory cytokines, including the adipokines leptin and adiponectin at ~38 weeks in 250 healthy women.<br><br>RESULTS: We found a number of associations, including, but not limited to those of adiponectin with C22:3/C22:4 (coeff -1.44; p = 0.008), C18:1 c13/c14 (coeff 1.4; p = 0.02); endotoxin with C20:1 (coeff -0.9; p = 0.03), C22:0 (coeff -0.4; p = 0.05); MCP-1 with C16:0 (coeff 0.8; p = 0.04); and ICAM-1 with C14:0 (coeff -86.8; p = 0.045). Several cytokines including leptin were associated with maternal body weight (coeff 0.9; p = 2.31 &#xd7; 10[-5]), smoking habits (i.e., ICAM-1 coeff 133.3; p = 0.09), or gestational diabetes (i.e., ICAM-1 coeff 688; p = 0.06).<br><br>CONCLUSIONS: In a general cohort of pregnant women, the intake of fatty acids influenced the balance between pro- and anti-inflammatory molecules together with weight gain, smoking habits, and gestational diabetes.}, }
@article {pmid37298483, year = {2023}, author = {Park, S and Zhang, T and Kang, S}, title = {Fecal Microbiota Composition, Their Interactions, and Metagenome Function in US Adults with Type 2 Diabetes According to Enterotypes.}, journal = {International journal of molecular sciences}, volume = {24}, number = {11}, pages = {}, pmid = {37298483}, issn = {1422-0067}, support = {RS-2023-00208567//National Research Foundation of Korea/ ; }, mesh = {Adult ; Humans ; Metagenome ; *Diabetes Mellitus, Type 2/genetics ; *Microbiota ; *Gastrointestinal Microbiome/genetics ; Feces/microbiology ; Bacteria/genetics ; }, abstract = {T2DM etiology differs among Asians and Caucasians and may be associated with gut microbiota influenced by different diet patterns. However, the association between fecal bacterial composition, enterotypes, and T2DM susceptibility remained controversial. We investigated the fecal bacterial composition, co-abundance network, and metagenome function in US adults with T2DM compared to healthy adults based on enterotypes. We analyzed 1911 fecal bacterial files of 1039 T2DM and 872 healthy US adults from the Human Microbiome Projects. Operational taxonomic units were obtained after filtering and cleaning the files using Qiime2 tools. Machine learning and network analysis identified primary bacteria and their interactions influencing T2DM incidence, clustered into enterotypes, Bacteroidaceae (ET-B), Lachnospiraceae (ET-L), and Prevotellaceae (ET-P). ET-B showed higher T2DM incidence. Alpha-diversity was significantly lower in T2DM in ET-L and ET-P (p < 0.0001), but not in ET-B. Beta-diversity revealed a distinct separation between T2DM and healthy groups across all enterotypes (p < 0.0001). The XGBoost model exhibited high accuracy and sensitivity. Enterocloster bolteae, Facalicatena fissicatena, Clostridium symbiosum, and Facalibacterium prausnitizii were more abundant in the T2DM group than in the healthy group. Bacteroides koreensis, Oscillibacter ruminantium, Bacteroides uniformis, and Blautia wexlerae were lower in the T2DM than in the healthy group regardless of the enterotypes in the XGBoost model (p < 0.0001). However, the patterns of microbial interactions varied among different enterotypes affecting T2DM risk. The interaction between fecal bacteria was more tightly regulated in the ET-L than in the ET-B and ET-P groups (p < 0.001). Metagenomic analysis revealed an inverse association between bacteria abundance in T2DM, energy utility, butanoate and propanoate metabolism, and the insulin signaling pathway (p < 0.0001). In conclusion, fecal bacteria play a role in T2DM pathogenesis, particularly within different enterotypes, providing valuable insights into the link between gut microbiota and T2DM in the US population.}, }
@article {pmid37293045, year = {2023}, author = {Zhao, L and Cunningham, CM and Andruska, AM and Schimmel, K and Ali, MK and Kim, D and Gu, S and Chang, JL and Spiekerkoetter, E and Nicolls, MR}, title = {Rat microbial biogeography and age-dependent lactic acid bacteria in healthy lungs.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2023.05.19.541527}, pmid = {37293045}, issn = {2692-8205}, abstract = {The laboratory rat emerges as a useful tool for studying the interaction between the host and its microbiome. To advance principles relevant to the human microbiome, we systematically investigated and defined a multi-tissue full lifespan microbial biogeography for healthy Fischer 344 rats. Microbial community profiling data was extracted and integrated with host transcriptomic data from the Sequencing Quality Control (SEQC) consortium. Unsupervised machine learning, Spearman's correlation, taxonomic diversity, and abundance analyses were performed to determine and characterize the rat microbial biogeography and the identification of four inter-tissue microbial heterogeneity patterns (P1-P4). The 11 body habitats harbor a greater diversity of microbes than previously suspected. Lactic acid bacteria (LAB) abundances progressively declined in lungs from breastfeed newborn to adolescence/adult and was below detectable levels in elderly rats. LAB's presence and levels in lungs were further evaluated by PCR in the two validation datasets. The lung, testes, thymus, kidney, adrenal, and muscle niches were found to have age-dependent alterations in microbial abundance. P1 is dominated by lung samples. P2 contains the largest sample size and is enriched for environmental species. Liver and muscle samples were mostly classified into P3. Archaea species were exclusively enriched in P4. The 357 pattern-specific microbial signatures were positively correlated with host genes in cell migration and proliferation (P1), DNA damage repair and synaptic transmissions (P2), as well as DNA transcription and cell cycle in P3. Our study established a link between metabolic properties of LAB with lung microbiota maturation and development. Breastfeeding and environmental exposure influence microbiome composition and host health and longevity. The inferred rat microbial biogeography and pattern-specific microbial signatures would be useful for microbiome therapeutic approaches to human health and good quality of life.}, }
@article {pmid37287813, year = {2023}, author = {Koizumi, Y and Maruyama, F}, title = {Editorial: Ecology, environment, and human microbiome interaction with infection.}, journal = {Frontiers in public health}, volume = {11}, number = {}, pages = {1217927}, doi = {10.3389/fpubh.2023.1217927}, pmid = {37287813}, issn = {2296-2565}, mesh = {Humans ; *Microbiota ; *Gastrointestinal Microbiome ; }, }
@article {pmid37280117, year = {2023}, author = {Scaldaferri, F and D'Onofrio, AM and Calia, R and Di Vincenzo, F and Ferrajoli, GF and Petito, V and Maggio, E and Pafundi, PC and Napolitano, D and Masi, L and Schiavoni, E and Fanali, C and Puca, P and Turchini, L and Lopetuso, LR and Del Chierico, F and Putignani, L and Gasbarrini, A and Camardese, AG}, title = {Gut Microbiota Signatures Are Associated With Psychopathological Profiles in Patients With Ulcerative Colitis: Results From an Italian Tertiary IBD Center.}, journal = {Inflammatory bowel diseases}, volume = {29}, number = {11}, pages = {1805-1818}, pmid = {37280117}, issn = {1536-4844}, mesh = {Humans ; *Colitis, Ulcerative/pathology ; *Gastrointestinal Microbiome ; Longitudinal Studies ; *Depressive Disorder, Major/complications ; Prospective Studies ; Quality of Life ; Bacteria ; }, abstract = {BACKGROUND: Several patients with ulcerative colitis (UC) suffer from psychiatric disorders, such as major depressive disorder, anxiety, or bipolar disorder, and show specific personality traits. Despite this, there are few data about personality profiles' characterization in UC patients and about correlation of their psychopathological profile with their intestinal microbiota.The aim of our study is to analyze the psychopathological and personality profile of UC patients and correlate it with specific signatures of their gut microbiota.<br><br>METHODS: This is a prospective interventional longitudinal cohort study. We enrolled consecutive patients affected by UC attending to the IBD Unit of Center for Digestive Disease of "A. Gemelli" IRCCS Hospital in Rome and a group of healthy subjects, matched for specific characteristics. Each patient was evaluated by a gastroenterologist and a psychiatrist. Moreover, all participants underwent psychological tests and a collection of stool samples.<br><br>RESULTS: We recruited 39 UC patients and 37 healthy subjects. Most patients showed high level of alexithymia, anxiety symptoms, depressive symptoms, as well as neuroticism and hypochondria, with obsessive-compulsive features at the behavioral level, which significantly impaired their quality of life and abilities at work. Gut microbiota analysis in UC patients demonstrated an increase in actinobacteria, Proteobacteria and Saccharibacteria (TM7), with a reduction in verrucomicrobia, euryarchaeota and tenericutes.<br><br>CONCLUSIONS: Our study confirmed the presence of high levels of psycho-emotional distress in UC patients, alongside alterations of the intestinal microbiota, and highlighted some families and genera of bacteria (Enterobacteriaceae, Streptococcus, Veillonella, Klebsiella, and Clostridiaceae) as potential markers of an altered gut-brain axis in these patients.}, }
@article {pmid37279589, year = {2023}, author = {Ericson, JE and Burgoine, K and Kumbakumba, E and Ochora, M and Hehnly, C and Bajunirwe, F and Bazira, J and Fronterre, C and Hagmann, C and Kulkarni, AV and Kumar, MS and Magombe, J and Mbabazi-Kabachelor, E and Morton, SU and Movassagh, M and Mugamba, J and Mulondo, R and Natukwatsa, D and Kaaya, BN and Olupot-Olupot, P and Onen, J and Sheldon, K and Smith, J and Ssentongo, P and Ssenyonga, P and Warf, B and Wegoye, E and Zhang, L and Kiwanuka, J and Paulson, JN and Broach, JR and Schiff, SJ}, title = {Neonatal Paenibacilliosis: Paenibacillus Infection as a Novel Cause of Sepsis in Term Neonates With High Risk of Sequelae in Uganda.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {77}, number = {5}, pages = {768-775}, pmid = {37279589}, issn = {1537-6591}, support = {DP1 HD086071/HD/NICHD NIH HHS/United States ; KL2 TR002015/TR/NCATS NIH HHS/United States ; R01 AI145057/AI/NIAID NIH HHS/United States ; }, mesh = {Infant, Newborn ; Humans ; Female ; Pregnancy ; *Neonatal Sepsis ; Uganda/epidemiology ; *Sepsis/complications/epidemiology/drug therapy ; Anti-Bacterial Agents/therapeutic use ; *Hydrocephalus ; Disease Progression ; *Paenibacillus ; }, abstract = {BACKGROUND: Paenibacillus thiaminolyticus may be an underdiagnosed cause of neonatal sepsis.<br><br>METHODS: We prospectively enrolled a cohort of 800 full-term neonates presenting with a clinical diagnosis of sepsis at 2 Ugandan hospitals. Quantitative polymerase chain reaction specific to P. thiaminolyticus and to the Paenibacillus genus were performed on the blood and cerebrospinal fluid (CSF) of 631 neonates who had both specimen types available. Neonates with Paenibacillus genus or species detected in either specimen type were considered to potentially have paenibacilliosis, (37/631, 6%). We described antenatal, perinatal, and neonatal characteristics, presenting signs, and 12-month developmental outcomes for neonates with paenibacilliosis versus clinical sepsis due to other causes.<br><br>RESULTS: Median age at presentation was 3 days (interquartile range 1, 7). Fever (92%), irritability (84%), and clinical signs of seizures (51%) were common. Eleven (30%) had an adverse outcome: 5 (14%) neonates died during the first year of life; 5 of 32 (16%) survivors developed postinfectious hydrocephalus (PIH) and 1 (3%) additional survivor had neurodevelopmental impairment without hydrocephalus.<br><br>CONCLUSIONS: Paenibacillus species was identified in 6% of neonates with signs of sepsis who presented to 2 Ugandan referral hospitals; 70% were P. thiaminolyticus. Improved diagnostics for neonatal sepsis are urgently needed. Optimal antibiotic treatment for this infection is unknown but ampicillin and vancomycin will be ineffective in many cases. These results highlight the need to consider local pathogen prevalence and the possibility of unusual pathogens when determining antibiotic choice for neonatal sepsis.}, }
@article {pmid37265934, year = {2023}, author = {Kedia, S and Ahuja, V}, title = {Human gut microbiome: A primer for the clinician.}, journal = {JGH open : an open access journal of gastroenterology and hepatology}, volume = {7}, number = {5}, pages = {337-350}, pmid = {37265934}, issn = {2397-9070}, abstract = {The human host gets tremendously influenced by a genetically and phenotypically distinct and heterogeneous constellation of microbial species-the human microbiome-the gut being one of the most densely populated and characterized site for these organisms. Microbiome science has advanced rapidly, technically with respect to the analytical methods and biologically with respect to its mechanistic influence in health and disease states. A clinician conducting a microbiome study should be aware of the nuances related to microbiome research, especially with respect to the technical and biological factors that can influence the interpretation of research outcomes. Hence, this review is an attempt to detail these aspects of the human gut microbiome, with emphasis on its determinants in a healthy state.}, }
@article {pmid37265494, year = {2023}, author = {Chen, H and Sun, R and Wang, J and Yao, S and Batool, SS and Yu, Z and Huang, S and Huang, J}, title = {Bacillus amyloliquefaciens alleviates the pathological injuries in mice infected with Schistosoma japonicum by modulating intestinal microbiome.}, journal = {Frontiers in cellular and infection microbiology}, volume = {13}, number = {}, pages = {1172298}, pmid = {37265494}, issn = {2235-2988}, mesh = {Animals ; Mice ; *Schistosoma japonicum ; Liver Cirrhosis/pathology ; *Bacillus amyloliquefaciens ; *Gastrointestinal Microbiome ; RNA, Ribosomal, 16S/genetics ; Liver/pathology ; Mammals ; }, abstract = {Schistosoma japonicum causes serious pathological organ damage and alteration of the intestinal microbiome in the mammalian host, threatening the health of millions of people in China. Bacillus amyloliquefaciens has been reported to be able to alleviate the damage to the gut and liver and maintain the homeostasis of the intestinal microenvironment. However, it was unclear whether B. amyloliquefaciens could alleviate the hepatic and intestinal symptoms caused by S. japonicum. In this study, the intragastric administration of B. amyloliquefaciens was performed to treat S. japonicum-infected mice during the acute phase. Histopathological analysis and 16S rRNA gene sequencing were used to evaluate the pathological damage and changes in the intestinal microbiome. The results of the study showed that B. amyloliquefaciens treatment significantly reduced the degree of granuloma and fibrosis in infected mice. Additionally, recovery of diversity in the intestinal microbiome, decrease in the relative abundance of potential pathogenic bacteria such as Escherichia-Shigella, and reshaping of the interactive network between genera in the intestine were also observed after treatment with B. amyloliquefaciens. Our findings indicated that treatment with B. amyloliquefaciens effectively alleviated the pathological injuries of the liver and intestine in mice infected with S. japonicum by modulating the intestinal microbiome, implying that this probiotic can function as an effective therapeutic agent against schistosomiasis. We hope our study will provide auxiliary strategies and methods for the early prevention of schistosomiasis japonica.}, }
@article {pmid39808466, year = {2023}, author = {Kolář, M}, title = {[Selected aspects of the human microbiome].}, journal = {Klinicka mikrobiologie a infekcni lekarstvi}, volume = {29}, number = {2}, pages = {46-51}, pmid = {39808466}, issn = {1211-264X}, abstract = {This review briefly defines the term microbiome and characterizes its importance in health and disease.}, }
@article {pmid37257272, year = {2023}, author = {Li, F and Lai, J and Ma, F and Cai, Y and Li, S and Feng, Z and Lu, Z and Liu, X and Ke, Q and Hao, H and Xiao, X}, title = {Maternal melatonin supplementation shapes gut microbiota and protects against inflammation in early life.}, journal = {International immunopharmacology}, volume = {120}, number = {}, pages = {110359}, doi = {10.1016/j.intimp.2023.110359}, pmid = {37257272}, issn = {1878-1705}, mesh = {Female ; Mice ; Animals ; *Melatonin/pharmacology/therapeutic use ; Butyric Acid/pharmacology ; Lipopolysaccharides/pharmacology ; *Gastrointestinal Microbiome ; Inflammation/drug therapy ; Fatty Acids, Volatile ; *Intestinal Diseases ; Dietary Supplements ; }, abstract = {BACKGROUND: Gut microbiota colonization is critical for immune education and nutrient metabolism. Research shows that melatonin has beneficial effects as a therapy for many diseases via modulating gut dysbiosis. However, it is unclear whether melatonin alters gut microbiota colonization in early life.<br><br>METHODS: In the experimental group (Mel), mice were intraperitoneally injected with melatonin at 10&#xa0;mg/kg body weight for embryonic days 14-16 and received drinking water containing 0.4&#xa0;mg/mL melatonin until 28&#xa0;days postpartum. In the control group (Ctrl), mice were injected with the same volume of 2.5% ethanol in saline and provided with standard water. Two more groups were created by treating neonatal mice with 20&#xa0;mg/kg lipopolysaccharide (LPS) to induce inflammation, resulting in the groups Ctrl&#xa0;+&#xa0;LPS and Mel&#xa0;+&#xa0;LPS, respectively. We examined the gut microbiota of the neonatal mice in the Ctrl and Mel group on Days 7, 14, 21, and 28 post-birth. On Day 14, melatonin and short-chain fatty acids (SCFAs) concentrations were measured in the Ctrl and Mel group and the mice were treated with LPS to be evaluated for intestinal injury and inflammatory response 15&#xa0;h post treatment. According to the result of the SCFAs concentrations, some neonatal mice were intraperitoneally injected with 500&#xa0;mg/kg sodium butyrate (SB) from Days 11-13, intraperitoneally injected with 20&#xa0;mg/kg LPS on Day 14, and then euthanized by carbon dioxide inhalation the next morning. Intestinal injury and inflammatory responses were evaluated in the Ctrl&#xa0;+&#xa0;LPS and SB&#xa0;+&#xa0;LPS groups, respectively.<br><br>RESULTS: By Day 14, it was evident that maternal melatonin supplementation significantly increased the relative abundance of Firmicutes in the ileal [61.03 (35.35 - 76.18) % vs. 98.02 (86.61 - 99.01) %, P&#xa0;=&#xa0;0.003] and colonic [73.88 (69.77 - 85.99) % vs. 96.16 (94.57 - 96.34) %, P&#xa0;=&#xa0;0.04] microbiota, the concentration of melatonin (0.79&#xa0;&#xb1;&#xa0;0.49&#xa0;ng/ml vs. 6.11&#xa0;&#xb1;&#xa0;3.48&#xa0;ng/ml, P&#xa0;=&#xa0;0.008) in the gut lumen, and the fecal butyric acid (12.91&#xa0;&#xb1;&#xa0;5.74&#xa0;&#x3bc;g/g vs. 23.58&#xa0;&#xb1;&#xa0;10.71&#xa0;&#x3bc;g/g, P&#xa0;=&#xa0;0.026) concentration of neonatal mice. Melatonin supplementation, and sodium butyrate treatment markedly alleviated intestinal injury and decreased inflammatory factors in neonatal mice.<br><br>CONCLUSION: This study suggests that maternal melatonin supplementation can shape the gut microbiota and metabolism of offspring under normal physiological conditions and protect them against LPS-induced inflammation in early life.}, }
@article {pmid37251147, year = {2023}, author = {Nurxat, N and Wang, L and Wang, Q and Li, S and Jin, C and Shi, Y and Wulamu, A and Zhao, N and Wang, Y and Wang, H and Li, M and Liu, Q}, title = {Commensal Staphylococcus epidermidis Defends against Staphylococcus aureus through SaeRS Two-Component System.}, journal = {ACS omega}, volume = {8}, number = {20}, pages = {17712-17718}, pmid = {37251147}, issn = {2470-1343}, abstract = {Staphylococcus aureus is a high-virulent Gram-positive pathogen that is responsible for a serious of diseases. The emergence of antibiotic-resistant S. aureus poses a significant challenge in terms of treatment. The recent research on the human microbiome suggested that the application of commensal bacteria is a new strategy for combating pathogenic infections. Staphylococcus epidermidis, one of the most abundant species in the nasal microbiome, is able to inhibit the colonization of S. aureus. However, during bacterial competition, S. aureus undergoes evolutionary changes to adapt to the diverse environment. Our study has demonstrated that the nasal colonized S. epidermidis possesses the ability to inhibit the hemolytic activity of S. aureus. Moreover, we deciphered another layer of mechanism to inhibit S. aureus colonization by S. epidermidis. The active component present in the cell-free culture of S. epidermidis was found to significantly reduce the hemolytic activity of S. aureus in SaeRS- and Agr-dependent manner. Specifically, the hemolytic inhibition on the S. aureus Agr-I type by S. epidermidis is primarily dependent on the SaeRS two-component system. The active component is characterized as a small molecule that is heat sensitive and protease resistant. Critically, S. epidermidis significantly inhibit the virulence of S. aureus in a mouse skin abscess model, suggesting that the active compound could potentially be used as a therapeutic agent for managing S. aureus infections.}, }
@article {pmid37249060, year = {2023}, author = {Wolf, M and Schallert, K and Knipper, L and Sickmann, A and Sczyrba, A and Benndorf, D and Heyer, R}, title = {Advances in the clinical use of metaproteomics.}, journal = {Expert review of proteomics}, volume = {20}, number = {4-6}, pages = {71-86}, doi = {10.1080/14789450.2023.2215440}, pmid = {37249060}, issn = {1744-8387}, mesh = {Humans ; *Proteomics/methods ; *Microbiota/genetics ; Bacterial Proteins/metabolism ; Computational Biology/methods ; Obesity ; }, abstract = {INTRODUCTION: Investigating the taxonomic and functional composition of human microbiomes can aid in the understanding of disease etiologies, diagnosis, and therapy monitoring for several diseases, including inflammatory bowel disease or obesity. One method for microbiome monitoring is metaproteomics, which assesses human and microbial proteins and thus enables the study of host-microbiome interactions. This advantage led to increased interest in metaproteome analyses and significant developments to introduce this method into a clinical context.<br><br>AREAS COVERED: This review summarizes the recent progress from a technical side and an application-related point of view.<br><br>EXPERT OPINION: Numerous publications imply the massive potential of metaproteomics to impact human health care. However, the key challenges of standardization and validation of experimental and bioinformatic workflows and accurate quantification methods must be overcome.}, }
@article {pmid37244386, year = {2023}, author = {Zhang, Y and Chen, T and Hao, X and Hu, Y and Chen, M and Zhang, D and Cai, H and Luo, J and Kong, L and Huang, S and Huang, Y and Yang, N and Liu, R and Li, Q and Yuan, C and Wang, C and Zhou, H and Huang, W and Zhang, W}, title = {Mapping the regulatory effects of herbal organic compounds on gut bacteria.}, journal = {Pharmacological research}, volume = {193}, number = {}, pages = {106804}, doi = {10.1016/j.phrs.2023.106804}, pmid = {37244386}, issn = {1096-1186}, mesh = {Humans ; Mice ; Animals ; Bacteria ; *Plants, Medicinal ; Terpenes ; *Alkaloids ; Flavonoids/pharmacology ; Phenols ; }, abstract = {Herbal organic compounds (HOCs) are bioactive natural products from medicinal plants and some traditional Chinese medicines (TCMs). Recently, ingestion of a few HOCs with low bioavailability has been associated with alterations in gut microbiota, but the extent of this phenomenon remains unclear. Here, we systematically screened 481 HOCs against 47 representative gut bacterial strains in vitro and found that almost one-third of the HOCs exhibited unique anticommensal activity. Quinones showed a potent anticommensal activity, while saturated fatty acids exhibited stronger inhibition of the Lactobacillus genus. Flavonoids, phenylpropanoids, terpenoids, triterpenoids, alkaloids and phenols displayed weaker anticommensal activity, but steroids, saccharides and glycosides had hardly any effect on strain growth. Notably, S-configuration HOCs demonstrated stronger anticommensal activity than R-configuration HOCs. The strict screening conditions ensured high accuracy (95%) through benchmarking validation. Additionally, the effects of HOCs on human fecal microbiota profiling were positively correlated with their anticommensal activity against bacterial strains. Molecular and chemical features such as AATS3i and XLogP3 were correlated with the anticommensal activity of the HOCs in the random forest classifier. Finally, we validated that curcumin, a polyhydric phenol with anticommensal activity, improved insulin resistance in HFD mice by modulating the composition and metabolic function of gut microbiota. Our results systematically mapped the profile of HOCs directly affecting human gut bacterial strains, offering a resource for future research on HOC-microbiota interaction, and broadening our understanding of natural product utilization through gut microbiota modulation.}, }
@article {pmid37240974, year = {2023}, author = {Karakasidis, E and Kotsiou, OS and Gourgoulianis, KI}, title = {Lung and Gut Microbiome in COPD.}, journal = {Journal of personalized medicine}, volume = {13}, number = {5}, pages = {}, pmid = {37240974}, issn = {2075-4426}, abstract = {Chronic obstructive pulmonary disease (COPD) is one of the leading causes of death worldwide. The association between lung and gut microbiomes in the pathogenesis of COPD has been recently uncovered. The goal of this study was to discuss the role of the lung and gut microbiomes in COPD pathophysiology. A systematic search of the PubMed database for relevant articles submitted up to June 2022 was performed. We examined the association between the lung and gut microbiome dysbiosis, reflected in bronchoalveolar lavage (BAL), lung tissue, sputum, and feces samples, and the pathogenesis and progression of COPD. It is evident that the lung and gut microbiomes affect each other and both play a vital role in the pathogenesis of COPD. However, more research needs to be carried out to find the exact associations between microbiome diversity and COPD pathophysiology and exacerbation genesis. Another field that research should focus on is the impact of treatment interventions targeting the human microbiome in preventing COPD genesis and progression.}, }
@article {pmid37239856, year = {2023}, author = {Csader, S and Ismaiah, MJ and Kuningas, T and Heinäniemi, M and Suhonen, J and Männistö, V and Pentikäinen, H and Savonen, K and Tauriainen, MM and Galano, JM and Lee, JC and Rintamäki, R and Karisola, P and El-Nezami, H and Schwab, U}, title = {Twelve Weeks of High-Intensity Interval Training Alters Adipose Tissue Gene Expression but Not Oxylipin Levels in People with Non-Alcoholic Fatty Liver Disease.}, journal = {International journal of molecular sciences}, volume = {24}, number = {10}, pages = {}, pmid = {37239856}, issn = {1422-0067}, support = {813781//European Union's Horizon 2020 research and innovation program under the Marie Sk&#x142;odowska-Curie/ ; }, mesh = {Humans ; Female ; *Non-alcoholic Fatty Liver Disease/genetics/therapy/complications ; *High-Intensity Interval Training ; Adipose Tissue/metabolism ; Weight Loss ; Gene Expression ; Liver/metabolism ; }, abstract = {Lifestyle modifications, including increased physical activity and exercise, are recommended for non-alcoholic fatty liver disease (NAFLD). Inflamed adipose tissue (AT) contributes to the progression and development of NAFLD and oxylipins such as hydroxyeicosatetraenoic acids (HETE), hydroxydocosahexanenoic acids (HDHA), prostaglandins (PEG2), and isoprostanoids (IsoP), which all may play a role in AT homeostasis and inflammation. To investigate the role of exercise without weight loss on AT and plasma oxylipin concentrations in NAFLD subjects, we conducted a 12-week randomized controlled exercise intervention. Plasma samples from 39 subjects and abdominal subcutaneous AT biopsy samples from 19 subjects were collected both at the beginning and the end of the exercise intervention. In the AT of women, a significant reduction of gene expression of hemoglobin subunits (HBB, HBA1, HBA2) was observed within the intervention group during the 12-week intervention. Their expression levels were negatively associated with VO2max and maxW. In addition, pathways involved in adipocyte morphology alterations significantly increased, whereas pathways in fat metabolism, branched-chain amino acids degradation, and oxidative phosphorylation were suppressed in the intervention group (p < 0.05). Compared to the control group, in the intervention group, the ribosome pathway was activated, but lysosome, oxidative phosphorylation, and pathways of AT modification were suppressed (p < 0.05). Most of the oxylipins (HETE, HDHA, PEG2, and IsoP) in plasma did not change during the intervention compared to the control group. 15-F2t-IsoP significantly increased in the intervention group compared to the control group (p = 0.014). However, this oxylipin could not be detected in all samples. Exercise intervention without weight loss may influence the AT morphology and fat metabolism at the gene expression level in female NAFLD subjects.}, }
@article {pmid37237407, year = {2023}, author = {Schamarek, I and Anders, L and Chakaroun, RM and Kovacs, P and Rohde-Zimmermann, K}, title = {The role of the oral microbiome in obesity and metabolic disease: potential systemic implications and effects on taste perception.}, journal = {Nutrition journal}, volume = {22}, number = {1}, pages = {28}, pmid = {37237407}, issn = {1475-2891}, mesh = {Humans ; Taste Perception ; Obesity/complications ; *Metabolic Diseases ; Inflammation/complications ; *Gastrointestinal Microbiome ; }, abstract = {Obesity and its metabolic sequelae still comprise a challenge when it comes to understanding mechanisms, which drive these pandemic diseases. The human microbiome as a potential key player has attracted the attention of broader research for the past decade. Most of it focused on the gut microbiome while the oral microbiome has received less attention. As the second largest niche, the oral microbiome is associated with a multitude of mechanisms, which are potentially involved in the complex etiology of obesity and associated metabolic diseases. These mechanisms include local effects of oral bacteria on taste perception and subsequent food preference as well as systemic effects on adipose tissue function, the gut microbiome and systemic inflammation. This review summarizes a growing body of research, pointing towards a more prominent role of the oral microbiome in obesity and associated metabolic diseases than expected. Ultimately, our knowledge on the oral microbiome may support the development of new patient oriented therapeutic approaches inevitable to relieve the health burden of metabolic diseases and to reach long-term benefits in patients´ lives.}, }
@article {pmid37228387, year = {2023}, author = {Fung, DLX and Li, X and Leung, CK and Hu, P}, title = {A self-knowledge distillation-driven CNN-LSTM model for predicting disease outcomes using longitudinal microbiome data.}, journal = {Bioinformatics advances}, volume = {3}, number = {1}, pages = {vbad059}, pmid = {37228387}, issn = {2635-0041}, abstract = {MOTIVATION: Human microbiome is complex and highly dynamic in nature. Dynamic patterns of the microbiome can capture more information than single point inference as it contains the temporal changes information. However, dynamic information of the human microbiome can be hard to be captured due to the complexity of obtaining the longitudinal data with a large volume of missing data that in conjunction with heterogeneity may provide a challenge for the data analysis.<br><br>RESULTS: We propose using an efficient hybrid deep learning architecture convolutional neural network-long short-term memory, which combines with self-knowledge distillation to create highly accurate models to analyze the longitudinal microbiome profiles to predict disease outcomes. Using our proposed models, we analyzed the datasets from Predicting Response to Standardized Pediatric Colitis Therapy (PROTECT) study and DIABIMMUNE study. We showed the significant improvement in the area under the receiver operating characteristic curve scores, achieving 0.889 and 0.798 on PROTECT study and DIABIMMUNE study, respectively, compared with state-of-the-art temporal deep learning models. Our findings provide an effective artificial intelligence-based tool to predict disease outcomes using longitudinal microbiome profiles from collected patients.<br><br>The data and source code can be accessed at https://github.com/darylfung96/UC-disease-TL.}, }
@article {pmid37228370, year = {2023}, author = {Thijssen, M and Tacke, F and Van Espen, L and Cassiman, D and Naser Aldine, M and Nevens, F and Van Ranst, M and Matthijnssens, J and Pourkarim, MR}, title = {Plasma virome dynamics in chronic hepatitis B virus infected patients.}, journal = {Frontiers in microbiology}, volume = {14}, number = {}, pages = {1172574}, pmid = {37228370}, issn = {1664-302X}, abstract = {The virome remains an understudied domain of the human microbiome. The role of commensal viruses on the outcome of infections with known pathogens is not well characterized. In this study we aimed to characterize the longitudinal plasma virome dynamics in chronic hepatitis B virus (HBV) infected patients. Eighty-five longitudinal plasma samples were collected from 12 chronic HBV infected individuals that were classified in the four stages of HBV infection. The virome was characterized with an optimized viral extraction protocol and deep-sequenced on a NextSeq 2500 platform. The plasma virome was primarily composed of members of the Anello- Flavi-, and Hepadnaviridae (HBV) families. The virome structure and dynamics did not correlate with the different stages of chronic HBV infection nor with the administration of antiviral therapy. We observed a higher intrapersonal similarity of viral contigs. Genomic analysis of viruses observed in multiple timepoint demonstrated the presence of a dynamic community. This study comprehensively assessed the blood virome structure in chronic HBV infected individuals and provided insights in the longitudinal development of this viral community.}, }
@article {pmid37224760, year = {2023}, author = {Dixon, R and Egan, S and Hughes, S and Chapman, B}, title = {The Sexome - A proof of concept study into microbial transfer between heterosexual couples after sexual intercourse.}, journal = {Forensic science international}, volume = {348}, number = {}, pages = {111711}, doi = {10.1016/j.forsciint.2023.111711}, pmid = {37224760}, issn = {1872-6283}, mesh = {Humans ; Male ; Female ; *Coitus ; *Heterosexuality ; Proof of Concept Study ; RNA, Ribosomal, 16S/genetics ; DNA ; DNA Fingerprinting/methods ; Bacteria/genetics ; Microsatellite Repeats ; High-Throughput Nucleotide Sequencing ; }, abstract = {The detection and recovery of male DNA post-assault is important in sexual assault investigations, particularly where an offender is unknown to the victim. The collection of DNA evidence often occurs when the female victim undergoes a forensic medical assessment. Analysis regularly results in mixed autosomal DNA profiles with both victim and perpetrator DNA, often making it difficult to interpret a male profile suitable for DNA database searching. While short tandem repeat (STR) profiling of the male Y-chromosome is often used to overcome this challenge, successful identification of an individual can be hindered by the paternal inheritance pattern of Y-STRs and small Y-STR databases. Human microbiome research has suggested that a person's microbial diversity is unique. Therefore microbiome analysis using Massively Parallel Sequencing (MPS) could serve as a useful adjunct method of perpetrator identification. This study aimed to identify bacteria taxa that were unique to each participant and compare the bacterial communities found on their genitals both pre- and post-coitus. Samples were collected from six male-female sexual partner pairs. Volunteers were asked to self-collect low vaginal (females) and penis shaft and glans (males) samples before and after intercourse. Samples were extracted using the PureLink™ Microbiome DNA Purification Kit. Extracted DNA underwent library preparation using primers targeting the V3-V4 hypervariable regions of the bacterial 16S rRNA gene (∼450 bp). Libraries were sequenced on the Illumina MiSeq® platform. From the sequence data derived, statistical analysis was performed to investigate if bacteria sequences could be used to infer contact between each male-female pairing. Unique bacterial signatures were detected in low frequencies (<1%) in male and female participants pre-coitus. The data indicated a significant disruption to microbial diversity post-coitus in all samples. A transfer of the female microbiome during intercourse was most significant. As expected, one couple who did not use a barrier contraceptive yielded the most microbial transfer and disruption to diversity demonstrating a proof-of-concept in the utility of microbiome interrogation for sexual assault cases. Further genomic analysis is needed to confirm species and subspecies classification of bacteria that may produce a unique microbial profile that could then be used to identify a specific individual.}, }
@article {pmid37218407, year = {2023}, author = {Renardy, M and Prokopienko, AJ and Maxwell, JR and Flusberg, DA and Makaryan, S and Selimkhanov, J and Vakilynejad, M and Subramanian, K and Wille, L}, title = {A Quantitative Systems Pharmacology Model Describing the Cellular Kinetic-Pharmacodynamic Relationship for a Live Biotherapeutic Product to Support Microbiome Drug Development.}, journal = {Clinical pharmacology and therapeutics}, volume = {114}, number = {3}, pages = {633-643}, doi = {10.1002/cpt.2952}, pmid = {37218407}, issn = {1532-6535}, mesh = {Humans ; *Vancomycin ; Kinetics ; Network Pharmacology ; Drug Development ; *Microbiota ; }, abstract = {Live biotherapeutic products (LBPs) are human microbiome therapies showing promise in the clinic for a range of diseases and conditions. Describing the kinetics and behavior of LBPs poses a unique modeling challenge because, unlike traditional therapies, LBPs can expand, contract, and colonize the host digestive tract. Here, we present a novel cellular kinetic-pharmacodynamic quantitative systems pharmacology model of an LBP. The model describes bacterial growth and competition, vancomycin effects, binding and unbinding to the epithelial surface, and production and clearance of butyrate as a therapeutic metabolite. The model is calibrated and validated to published data from healthy volunteers. Using the model, we simulate the impact of treatment dose, frequency, and duration as well as vancomycin pretreatment on butyrate production. This model enables model-informed drug development and can be used for future microbiome therapies to inform decision making around antibiotic pretreatment, dose selection, loading dose, and dosing duration.}, }
@article {pmid37216534, year = {2023}, author = {Barbour, A and Smith, L and Oveisi, M and Williams, M and Huang, RC and Marks, C and Fine, N and Sun, C and Younesi, F and Zargaran, S and Orugunty, R and Horvath, TD and Haidacher, SJ and Haag, AM and Sabharwal, A and Hinz, B and Glogauer, M}, title = {Discovery of phosphorylated lantibiotics with proimmune activity that regulate the oral microbiome.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {120}, number = {22}, pages = {e2219392120}, pmid = {37216534}, issn = {1091-6490}, mesh = {Humans ; *Bacteriocins/pharmacology/chemistry ; Bacteria ; Anti-Bacterial Agents/pharmacology/chemistry ; Peptides ; }, abstract = {Lantibiotics are ribosomally synthesized and posttranslationally modified peptides (RiPPs) that are produced by bacteria. Interest in this group of natural products is increasing rapidly as alternatives to conventional antibiotics. Some human microbiome-derived commensals produce lantibiotics to impair pathogens' colonization and promote healthy microbiomes. Streptococcus salivarius is one of the first commensal microbes to colonize the human oral cavity and gastrointestinal tract, and its biosynthesis of RiPPs, called salivaricins, has been shown to inhibit the growth of oral pathogens. Herein, we report on a phosphorylated class of three related RiPPs, collectively referred to as salivaricin 10, that exhibit proimmune activity and targeted antimicrobial properties against known oral pathogens and multispecies biofilms. Strikingly, the immunomodulatory activities observed include upregulation of neutrophil-mediated phagocytosis, promotion of antiinflammatory M2 macrophage polarization, and stimulation of neutrophil chemotaxis-these activities have been attributed to the phosphorylation site identified on the N-terminal region of the peptides. Salivaricin 10 peptides were determined to be produced by S. salivarius strains found in healthy human subjects, and their dual bactericidal/antibiofilm and immunoregulatory activity may provide new means to effectively target infectious pathogens while maintaining important oral microbiota.}, }
@article {pmid37215849, year = {2023}, author = {Zhao, Z and Lin, J and Chen, S and Wang, X and Wang, H and Xu, G and Wang, J and Zhou, R and Huang, Z and Li, Y and Zhang, Y and Liu, X and Wang, P and Huang, M and Luo, Y and Yu, H}, title = {Clinical atlas of rectal cancer highlights the barriers and insufficient interventions underlying the unfavorable outcomes in older patients.}, journal = {Heliyon}, volume = {9}, number = {5}, pages = {e15966}, pmid = {37215849}, issn = {2405-8440}, abstract = {BACKGROUND: Aging confers an increased risk of developing cancer, and the global burden of cancer is cumulating as human longevity increases. Providing adequate care for old patients with rectal cancer is challenging and complex.<br><br>METHOD: A total of 428 and 44,788 patients diagnosed with non-metastatic rectal cancer from a referral tertiary care center (SYSU cohort) and the Surveillance Epidemiology and End Results database (SEER cohort) were included. Patients were categorized into old (over 65 years) and young (aged 50-65 years) groups. An age-specific clinical atlas of rectal cancer was generated, including the demographic and clinicopathological features, molecular profiles, treatment strategies, and clinical outcomes.<br><br>RESULTS: Old and young patients were similar in clinicopathological risk factors and molecular features, including TNM stage, tumor location, tumor differentiation, tumor morphology, lymphovascular invasion, and perineural invasion. However, old patients had significantly worse nutritional status and more comorbidities than young patients. In addition, old age was independently associated with less systemic cancer treatment (adjusted odds ratio 0.294 [95% CI 0.184-0.463, P&#xa0;<&#xa0;0.001]). We found that old patients had significantly worse overall survival (OS) outcomes in both SYSU (P&#xa0;<&#xa0;0.001) and SEER (P&#xa0;<&#xa0;0.001) cohorts. Moreover, the death and recurrence risk of old patients in the subgroup not receiving chemo/radiotherapy (P&#xa0;<&#xa0;0.001 for OS, and P&#xa0;=&#xa0;0.046 for time to recurrence [TTR]) reverted into no significant risk in the subgroup receiving chemo/radiotherapy.<br><br>CONCLUSIONS: Although old patients had similar tumor features to young patients, they had unfavorable survival outcomes associated with insufficient cancer care from old age. Specific trials with comprehensive geriatric assessment for old patients are needed to identify the optimal treatment regimens and improve unmet cancer care.<br><br>STUDY REGISTRATION: The study was registered on the research registry with the identifier of researchregistry 7635.}, }
@article {pmid37213403, year = {2023}, author = {Lahtinen, P and Jalanka, J and Mattila, E and Tillonen, J and Bergman, P and Satokari, R and Arkkila, P}, title = {Fecal microbiota transplantation for the maintenance of remission in patients with ulcerative colitis: A randomized controlled trial.}, journal = {World journal of gastroenterology}, volume = {29}, number = {17}, pages = {2666-2678}, pmid = {37213403}, issn = {2219-2840}, mesh = {Humans ; *Fecal Microbiota Transplantation/adverse effects/methods ; *Colitis, Ulcerative/diagnosis/therapy/etiology ; Quality of Life ; Remission Induction ; Feces ; Leukocyte L1 Antigen Complex ; }, abstract = {BACKGROUND: Fecal microbial transplantation (FMT) is a promising new method for treating active ulcerative colitis (UC), but knowledge regarding FMT for quiescent UC is scarce.<br><br>AIM: To investigate FMT for the maintenance of remission in UC patients.<br><br>METHODS: Forty-eight UC patients were randomized to receive a single-dose FMT or autologous transplant via colonoscopy. The primary endpoint was set to the maintenance of remission, a fecal calprotectin level below 200 &#x3bc;g/g, and a clinical Mayo score below three throughout the 12-mo follow-up. As secondary endpoints, we recorded the patient's quality of life, fecal calprotectin, blood chemistry, and endoscopic findings at 12 mo.<br><br>RESULTS: The main endpoint was achieved by 13 out of 24 (54%) patients in the FMT group and by 10 out of 24 (41%) patients in the placebo group (log-rank test, P = 0.660). Four months after FMT, the quality-of-life scores decreased in the FMT group compared to the placebo group (P = 0.017). In addition, the disease-specific quality of life measure was higher in the placebo group than in the FMT group at the same time point (P = 0.003). There were no differences in blood chemistry, fecal calprotectin, or endoscopic findings among the study groups at 12 mo. The adverse events were infrequent, mild, and distributed equally between the groups.<br><br>CONCLUSION: There were no differences in the number of relapses between the study groups at the 12-mo follow-up. Thus, our results do not support the use of a single-dose FMT for the maintenance of remission in UC.}, }
@article {pmid37211280, year = {2023}, author = {Chow, EWL and Pang, LM and Wang, Y}, title = {Impact of the host microbiota on fungal infections: New possibilities for intervention?.}, journal = {Advanced drug delivery reviews}, volume = {198}, number = {}, pages = {114896}, doi = {10.1016/j.addr.2023.114896}, pmid = {37211280}, issn = {1872-8294}, mesh = {Humans ; Antifungal Agents/pharmacology/therapeutic use ; *Mycoses/drug therapy ; Fungi ; *Microbiota ; Bacteria ; }, abstract = {Many human fungal pathogens are opportunistic. They are primarily benign residents of the human body and only become infectious when the host's immunity and microbiome are compromised. Bacteria dominate the human microbiome, playing an essential role in keeping fungi harmless and acting as the first line of defense against fungal infection. The Human Microbiome Project, launched by NIH in 2007, has stimulated extensive investigation and significantly advanced our understanding of the molecular mechanisms governing the interaction between bacteria and fungi, providing valuable insights for developing future antifungal strategies by exploiting the interaction. This review summarizes recent progress in this field and discusses new possibilities and challenges. We must seize the opportunities presented by researching bacterial-fungal interplay in the human microbiome to address the global spread of drug-resistant fungal pathogens and the drying pipelines of effective antifungal drugs.}, }
@article {pmid37208436, year = {2023}, author = {Winders, TM and Holman, DB and Schmidt, KN and Luecke, SM and Smith, DJ and Neville, BW and Dahlen, CR and Swanson, KC and Amat, S}, title = {Feeding hempseed cake alters the bovine gut, respiratory and reproductive microbiota.}, journal = {Scientific reports}, volume = {13}, number = {1}, pages = {8121}, pmid = {37208436}, issn = {2045-2322}, mesh = {Humans ; Cattle ; Animals ; Female ; Infant ; *Animal Feed/analysis ; RNA, Ribosomal, 16S/genetics ; *Diet/veterinary ; Silage/analysis ; Reproduction ; Zea mays/chemistry ; Rumen ; }, abstract = {A growing number of studies have investigated the feasibility of utilizing hemp by-products as livestock feedstuffs; however, their impact on livestock microbiomes remains unexplored. Here, we evaluated the effects of feeding hempseed cake on the gastrointestinal, respiratory, and reproductive microbiota in beef heifers. Angus-crossbred heifers (19-months old, initial body weight = 494 ± 10 kg [SE]) were fed a corn-based finishing diet containing 20% hempseed cake as a substitute for 20% corn dried distillers' grains with solubles (DM basis; Control; n = 16/group) for 111 days until slaughter. Ruminal fluid and deep nasopharyngeal swabs (days 0, 7, 42, 70 and 98), and vaginal and uterine swabs (at slaughter) were collected, and the microbiota assessed using 16S rRNA gene sequencing. Diet affected the community structure of the ruminal (d 7-98; 0.06 ≤ R[2] ≤ 0.12; P < 0.05), nasopharyngeal (d 98; R[2] = 0.18; P < 0.001), and vaginal (R[2] = 0.06; P < 0.01) microbiota. Heifers fed hempseed cake had increased microbial diversity in the rumen, reduced microbial richness in the vagina, and greater microbial diversity and richness in the uterus. In addition to the distinct microbial communities in the rumen, nasopharynx, vagina and uterus, we identified 28 core taxa that were shared (≥ 60% of all samples) across these sampling locations. Feeding hempseed cake appeared to alter the bovine gut, respiratory and reproductive microbiota. Our results suggest that future research aiming to evaluate the use of hemp by-products in livestock diet should consider their impact on animal microbiome and microbiome mediated animal health and reproductive efficiency. Our findings also highlight the need for research evaluating the impact of hemp-associated food and personal care products on the human microbiome.}, }
@article {pmid37205434, year = {2023}, author = {Inglis, LK and Roach, MJ and Edwards, RA}, title = {Prophage rates in the human microbiome vary by body site and host health.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {37205434}, issn = {2692-8205}, abstract = {Phages integrated into a bacterial genome-called prophages-continuously monitor the health of the host bacteria to determine when to escape the genome, protect their host from other phage infections, and may provide genes that promote bacterial growth. Prophages are essential to almost all microbiomes, including the human microbiome. However, most human microbiome studies focus on bacteria, ignoring free and integrated phages, so we know little about how these prophages affect the human microbiome. We compared the prophages identified in 11,513 bacterial genomes isolated from human body sites to characterise prophage DNA in the human microbiome. Here, we show that prophage DNA comprised an average of 1-5% of each bacterial genome. The prophage content per genome varies with the isolation site on the human body, the health of the human, and whether the disease was symptomatic. The presence of prophages promotes bacterial growth and sculpts the microbiome. However, the disparities caused by prophages vary throughout the body.}, }
@article {pmid37204436, year = {2023}, author = {Kodila, A and Franko, N and Sollner Dolenc, M}, title = {A review on immunomodulatory effects of BPA analogues.}, journal = {Archives of toxicology}, volume = {97}, number = {7}, pages = {1831-1846}, pmid = {37204436}, issn = {1432-0738}, support = {P1-0208//Javna Agencija za Raziskovalno Dejavnost RS/ ; Young Researcher grant//Javna Agencija za Raziskovalno Dejavnost RS/ ; Grant Agreement No 101057014//European Union's Horizon Europe research and innovation programme/ ; }, mesh = {Humans ; *Receptors, Cytoplasmic and Nuclear ; Phenols/toxicity ; Benzhydryl Compounds/toxicity ; Body Weight ; *Endocrine Disruptors/toxicity ; }, abstract = {Bisphenol A (BPA) is a known endocrine disruptor found in many consumer products that humans come into contact with on a daily basis. Due to increasing concerns about the safety of BPA and the introduction of new legislation restricting its use, industry has responded by adopting new, less studied BPA analogues that have similar polymer-forming properties. Some BPA analogues have already been shown to exhibit effects similar to BPA, for example, contributing to endocrine disruption through agonistic or antagonistic behaviour at various nuclear receptors such as estrogen (ER), androgen (AR), glucocorticoid (GR), aryl hydrocarbon (AhR), and pregnane X receptor (PXR). Since the European Food Safety Authority (EFSA) issued a draft re-evaluation of BPA and drastically reduced the temporary tolerable daily intake (t-TDI) of BPA from 4 mg/kg body weight/day to 0.2 ng/kg body weight/day due to increasing concern about the toxic properties of BPA, including its potential to disrupt immune system processes, we conducted a comprehensive review of the immunomodulatory activity of environmentally abundant BPA analogues. The results of the review suggest that BPA analogues may affect both the innate and acquired immune systems and can contribute to various immune-mediated conditions such as hypersensitivity reactions, allergies, and disruption of the human microbiome.}, }
@article {pmid37202853, year = {2023}, author = {Velsko, IM and Gallois, S and Stahl, R and Henry, AG and Warinner, C}, title = {High conservation of the dental plaque microbiome across populations with differing subsistence strategies and levels of market integration.}, journal = {Molecular ecology}, volume = {32}, number = {14}, pages = {3872-3891}, doi = {10.1111/mec.16988}, pmid = {37202853}, issn = {1365-294X}, mesh = {Humans ; *Dental Plaque ; *Microbiota/genetics ; Mouth ; Diet ; North America ; }, abstract = {Industrialization-including urbanization, participation in the global food chain and consumption of heavily processed foods-is thought to drive substantial shifts in the human microbiome. While diet strongly influences stool microbiome composition, the influence of diet on the oral microbiome is largely speculative. Multiple ecologically distinct surfaces in the mouth, each harbouring a unique microbial community, pose a challenge to assessing changes in the oral microbiome in the context of industrialization, as the results depend on the oral site under study. Here, we investigated whether microbial communities of dental plaque, the dense biofilm on non-shedding tooth surfaces, are distinctly different across populations with dissimilar subsistence strategies and degree of industrialized market integration. Using a metagenomic approach, we compared the dental plaque microbiomes of Baka foragers and Nzime subsistence agriculturalists in Cameroon (n = 46) with the dental plaque and calculus microbiomes of highly industrialized populations in North America and Europe (n = 38). We found that differences in microbial taxonomic composition between populations were minimal, with high conservation of abundant microbial taxa and no significant differences in microbial diversity related to dietary practices. Instead, we find that the major source of variation in dental plaque microbial species composition is related to tooth location and oxygen availability, which may be influenced by toothbrushing or other dental hygiene measures. Our results support that dental plaque, in contrast to the stool microbiome, maintains an inherent stability against ecological perturbations in the oral environment.}, }
@article {pmid37198426, year = {2023}, author = {Benincà, E and Pinto, S and Cazelles, B and Fuentes, S and Shetty, S and Bogaards, JA}, title = {Wavelet clustering analysis as a tool for characterizing community structure in the human microbiome.}, journal = {Scientific reports}, volume = {13}, number = {1}, pages = {8042}, pmid = {37198426}, issn = {2045-2322}, mesh = {Humans ; *Microbiota ; Wavelet Analysis ; *Gastrointestinal Microbiome ; Microbial Consortia ; Cluster Analysis ; }, abstract = {Human microbiome research is helped by the characterization of microbial networks, as these may reveal key microbes that can be targeted for beneficial health effects. Prevailing methods of microbial network characterization are based on measures of association, often applied to limited sampling points in time. Here, we demonstrate the potential of wavelet clustering, a technique that clusters time series based on similarities in their spectral characteristics. We illustrate this technique with synthetic time series and apply wavelet clustering to densely sampled human gut microbiome time series. We compare our results with hierarchical clustering based on temporal correlations in abundance, within and across individuals, and show that the cluster trees obtained by using either method are significantly different in terms of elements clustered together, branching structure and total branch length. By capitalizing on the dynamic nature of the human microbiome, wavelet clustering reveals community structures that remain obscured in correlation-based methods.}, }
@article {pmid37191901, year = {2023}, author = {Seidel, J and Magzamen, S and Wang, YH and Neujahr, V and Schaeffer, JW}, title = {Lessons from Dairy Farmers for Occupational Allergy and Respiratory Disease.}, journal = {Current allergy and asthma reports}, volume = {23}, number = {6}, pages = {325-339}, pmid = {37191901}, issn = {1534-6315}, support = {U54 OH008085/OH/NIOSH CDC HHS/United States ; R01 OH012046/OH/NIOSH CDC HHS/United States ; }, mesh = {Humans ; *Occupational Exposure/adverse effects ; Farmers ; *Respiration Disorders ; *Respiratory Tract Diseases/epidemiology/etiology ; *Hypersensitivity ; }, abstract = {PURPOSE OF REVIEW: Exposure to bioaerosols at dairies has long been associated with allergy, respiratory disease, and decreases in lung function. Recent advancements in exposure assessments have aided our understanding on the size distribution and composition of these bioaerosols, but investigations focusing solely on exposures may overlook important intrinsic factors impacting worker's susceptibility to disease.<br><br>RECENT FINDINGS: In our review, we discuss the most recent studies examining the exposures and genetic factors that contribute to occupational disease in dairy work. We also review more recent concerns in livestock work associated with zoonotic pathogens, antimicrobial resistant genes, and the role of the human microbiome. The studies highlighted in this review demonstrate the need for further research to better understand bioaerosol exposure-response relationships in the context of extrinsic and intrinsic factors, antibiotic-resistant genes, viral pathogens, and the human microbiome to help inform effective interventions that improve respiratory health among dairy farmers.}, }
@article {pmid37190067, year = {2023}, author = {Lupu, VV and Adam Raileanu, A and Mihai, CM and Morariu, ID and Lupu, A and Starcea, IM and Frasinariu, OE and Mocanu, A and Dragan, F and Fotea, S}, title = {The Implication of the Gut Microbiome in Heart Failure.}, journal = {Cells}, volume = {12}, number = {8}, pages = {}, pmid = {37190067}, issn = {2073-4409}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; Dysbiosis/microbiology ; *Heart Failure ; *Microbiota ; Risk Factors ; }, abstract = {Heart failure is a worldwide health problem with important consequences for the overall wellbeing of affected individuals as well as for the healthcare system. Over recent decades, numerous pieces of evidence have demonstrated that the associated gut microbiota represent an important component of human physiology and metabolic homeostasis, and can affect one's state of health or disease directly, or through their derived metabolites. The recent advances in human microbiome studies shed light on the relationship between the gut microbiota and the cardiovascular system, revealing its contribution to the development of heart failure-associated dysbiosis. HF has been linked to gut dysbiosis, low bacterial diversity, intestinal overgrowth of potentially pathogenic bacteria and a decrease in short chain fatty acids-producing bacteria. An increased intestinal permeability allowing microbial translocation and the passage of bacterial-derived metabolites into the bloodstream is associated with HF progression. A more insightful understanding of the interactions between the human gut microbiome, HF and the associated risk factors is mandatory for optimizing therapeutic strategies based on microbiota modulation and offering individualized treatment. The purpose of this review is to summarize the available data regarding the influence of gut bacterial communities and their derived metabolites on HF, in order to obtain a better understanding of this multi-layered complex relationship.}, }
@article {pmid37189783, year = {2023}, author = {Monticolo, M and Mucha, K and Foroncewicz, B}, title = {Lupus Nephritis and Dysbiosis.}, journal = {Biomedicines}, volume = {11}, number = {4}, pages = {}, pmid = {37189783}, issn = {2227-9059}, abstract = {Lupus nephritis (LN) is one of the most common and serious complications of systemic lupus erythematosus (SLE). The risk factors for developing LN by SLE patients are not fully understood. They are considered to be a mix of genetic and environmental variables, one of them being dysbiosis, proposed recently to interfere with autoimmunity. As of yet, the relations between the human microbiome, its genetic determinants, individual variability and clinical consequences remain to be established. One of the major obstacles in studying them is the magnitude of confounders, such as diet, drugs, infections or antibiotics use. They also make comparison between the studies extremely complicated. We reviewed the available evidence for the interplay between microbiome, dysbiosis and mechanisms triggering the autoimmune responses and potentially contributing to LN development. One such mechanism is the stimulation of autoimmune responses by bacterial metabolites that can mimic autoantigens and cause antibody production. These mimicking microbial antigens seem to be a promising target for future interventions.}, }
@article {pmid37180436, year = {2023}, author = {Che, Y and Wang, N and Ma, Q and Liu, J and Xu, Z and Li, Q and Wang, J and Sun, Y}, title = {Microbial characterization of the nasal cavity in patients with allergic rhinitis and non-allergic rhinitis.}, journal = {Frontiers in cellular and infection microbiology}, volume = {13}, number = {}, pages = {1166389}, pmid = {37180436}, issn = {2235-2988}, mesh = {Humans ; Male ; Female ; Young Adult ; Adult ; *Rhinitis, Allergic/microbiology ; *Rhinitis/microbiology ; *Nasal Cavity/microbiology ; Metagenome ; Biodiversity ; *Microbiota ; RNA, Ribosomal, 16S/analysis ; *Bacteria/classification/genetics/isolation &amp; purification ; }, abstract = {INTRODUCTION: Although recent studies have shown that the human microbiome is involved in the pathogenesis of allergic diseases, the impact of microbiota on allergic rhinitis (AR) and non-allergic rhinitis (nAR) has not been elucidated. The aim of this study was to investigate the differences in the composition of the nasal flora in patients with AR and nAR and their role in the pathogenesis.<br><br>METHOD: From February to September 2022, 35 AR patients and 35 nAR patients admitted to Harbin Medical University's Second Affiliated Hospital, as well as 20 healthy subjects who underwent physical examination during the same period, were subjected to 16SrDNA and metagenomic sequencing of nasal flora.<br><br>RESULTS: The microbiota composition of the three groups of study subjects differs significantly. The relative abundance of Vibrio vulnificus and Acinetobacter baumanni in the nasal cavity of AR patients was significantly higher when compared to nAR patients, while the relative abundance of Lactobacillus murinus, Lactobacillus iners, Proteobacteria, Pseudomonadales, and Escherichia coli was lower. In addition, Lactobacillus murinus and Lacttobacillus kunkeei were also negatively correlated with IgE, while Lacttobacillus kunkeei was positively correlated with age. The relative distribution of Faecalibacterium was higher in moderate than in severe AR patients. According to KEGG functional enrichment annotation, ICMT(protein-S-isoprenylcysteine O-methyltransferase,ICMT) is an AR microbiota-specific enzyme that plays a role, while glycan biosynthesis and metabolism are more active in AR microbiota. For AR, the model containing Parabacteroides goldstemii, Sutterella-SP-6FBBBBH3, Pseudoalteromonas luteoviolacea, Lachnospiraceae bacterium-615, and Bacteroides coprocola had the highest the area under the curve (AUC), which was 0.9733(95%CI:0.926-1.000) in the constructed random forest prediction model. The largest AUC for nAR is 0.984(95%CI:0.949-1.000) for the model containing Pseudomonas-SP-LTJR-52, Lachnospiraceae bacterium-615, Prevotella corporis, Anaerococcus vaginalis, and Roseburia inulinivorans.<br><br>CONCLUSION: In conclusion, patients with AR and nAR had significantly different microbiota profiles compared to healthy controls. The results suggest that the nasal microbiota may play a key role in the pathogenesis and symptoms of AR and nAR, providing us with new ideas for the treatment of AR and nAR.}, }
@article {pmid37178069, year = {2023}, author = {Bracaglia, C and Marucci, G and Del Chierico, F and Russo, A and Pardeo, M and Pires Marafon, D and Quagliariello, A and Caiello, I and Rea, F and Fingerhutova, S and Insalaco, A and Prencipe, G and Dolezalova, P and De Benedetti, F and Putignani, L}, title = {Microbiota transplant to control inflammation in a patient with NLRC4 gain-of-function-induced disease.}, journal = {The Journal of allergy and clinical immunology}, volume = {152}, number = {1}, pages = {302-303}, doi = {10.1016/j.jaci.2023.03.031}, pmid = {37178069}, issn = {1097-6825}, mesh = {Humans ; *Gain of Function Mutation ; *Inflammation ; CARD Signaling Adaptor Proteins/genetics ; Calcium-Binding Proteins/genetics ; Inflammasomes ; }, }
@article {pmid37174009, year = {2023}, author = {Munteanu, R and Feder, RI and Onaciu, A and Munteanu, VC and Iuga, CA and Gulei, D}, title = {Insights into the Human Microbiome and Its Connections with Prostate Cancer.}, journal = {Cancers}, volume = {15}, number = {9}, pages = {}, pmid = {37174009}, issn = {2072-6694}, abstract = {The human microbiome represents the diversity of microorganisms that live together at different organ sites, influencing various physiological processes and leading to pathological conditions, even carcinogenesis, in case of a chronic imbalance. Additionally, the link between organ-specific microbiota and cancer has attracted the interest of numerous studies and projects. In this review article, we address the important aspects regarding the role of gut, prostate, urinary and reproductive system, skin, and oral cavity colonizing microorganisms in prostate cancer development. Various bacteria, fungi, virus species, and other relevant agents with major implications in cancer occurrence and progression are also described. Some of them are assessed based on their values of prognostic or diagnostic biomarkers, while others are presented for their anti-cancer properties.}, }
@article {pmid37173453, year = {2023}, author = {Baba, Y and Hara, Y and Toihata, T and Kosumi, K and Iwatsuki, M and Iwagami, S and Miyamoto, Y and Yoshida, N and Komohara, Y and Baba, H}, title = {Relationship between gut microbiome Fusobacterium nucleatum and LINE-1 methylation level in esophageal cancer.}, journal = {Esophagus : official journal of the Japan Esophageal Society}, volume = {20}, number = {4}, pages = {704-712}, pmid = {37173453}, issn = {1612-9067}, mesh = {Humans ; Fusobacterium nucleatum/genetics ; Methylation ; *Gastrointestinal Microbiome/genetics ; *Colorectal Neoplasms/genetics/microbiology/pathology ; *Esophageal Neoplasms/genetics/pathology ; }, abstract = {BACKGROUND: We previously demonstrated the relationship of human microbiome Fusobacterium nucleatum with unfavorable clinical outcomes and inferior chemotherapeutic responses in esophageal cancer. Global DNA methylation is associated with the occurrence and development of various cancers. In our previous study, LINE-1 hypomethylation (i.e., global DNA hypomethylation) was associated with a poor prognosis in esophageal cancer. As the gut microbiota may play crucial roles in the DNA methylation of host cells, we hypothesized that F. nucleatum might influence LINE-1 methylation levels in esophageal cancer.<br><br>METHODS: We qualified the F. nucleatum DNA using a quantitative PCR assay and LINE-1 methylation via a pyrosequencing assay using formalin-fixed paraffin-embedded specimens from 306 esophageal cancer patients.<br><br>RESULTS: Intratumoral F. nucleatum DNA was detected in 65 cases (21.2%). The LINE-1 methylation scores ranged from 26.9 to 91.8 (median&#x2009;=&#x2009;64.8) in tumors. F. nucleatum DNA was related to the LINE-1 hypomethylation of tumor lesions in esophageal cancer (P&#x2009;<&#x2009;0.0001). The receiver operating characteristic curve analysis showed that the area under the curve was 0.71 for F. nucleatum positivity. Finally, we found that the impact of F. nucleatum on clinical outcomes was not modified by LINE-1 hypomethylation (P for interaction&#x2009;=&#x2009;0.34).<br><br>CONCLUSIONS: F. nucleatum alters genome-wide methylation levels in cancer cells, which may be one of the mechanisms by which F. nucleatum affects the malignant behavior of esophageal cancer.}, }
@article {pmid37173385, year = {2023}, author = {Dave, A and Beyoğlu, D and Park, EJ and Idle, JR and Pezzuto, JM}, title = {Influence of grape consumption on the human microbiome.}, journal = {Scientific reports}, volume = {13}, number = {1}, pages = {7706}, pmid = {37173385}, issn = {2045-2322}, support = {P30 CA008748/CA/NCI NIH HHS/United States ; }, mesh = {Humans ; Male ; Female ; Young Adult ; Adult ; Middle Aged ; *Vitis/metabolism ; Diet ; *Microbiota ; Plasma ; Metabolomics ; }, abstract = {Over the years, a substantial body of information has accumulated suggesting dietary consumption of grapes may have a positive influence on human health. Here, we investigate the potential of grapes to modulate the human microbiome. Microbiome composition as well as urinary and plasma metabolites were sequentially assessed in 29 healthy free-living male (age 24-55 years) and female subjects (age 29-53 years) following two-weeks of a restricted diet (Day 15), two-weeks of a restricted diet with grape consumption (equivalent to three servings per day) (Day 30), and four-weeks of restricted diet without grape consumption (Day 60). Based on alpha-diversity indices, grape consumption did not alter the overall composition of the microbial community, other than with the female subset based on the Chao index. Similarly, based on beta-diversity analyses, the diversity of species was not significantly altered at the three time points of the study. However, following 2 weeks of grape consumption, taxonomic abundance was altered (e.g., decreased Holdemania spp. and increased Streptococcus thermophiles), as were various enzyme levels and KEGG pathways. Further, taxonomic, enzyme and pathway shifts were observed 30 days following the termination of grape consumption, some of which returned to baseline and some of which suggest a delayed effect of grape consumption. Metabolomic analyses supported the functional significance of these alterations wherein, for example, 2'-deoxyribonic acid, glutaconic acid, and 3-hydroxyphenylacetic acid were elevated following grape consumption and returned to baseline following the washout period. Inter-individual variation was observed and exemplified by analysis of a subgroup of the study population showing unique patterns of taxonomic distribution over the study period. The biological ramifications of these dynamics remain to be defined. However, while it seems clear that grape consumption does not perturb the eubiotic state of the microbiome with normal, healthy human subjects, it is likely that shifts in the intricate interactive networks that result from grape consumption have physiological significance of relevance to grape action.}, }
@article {pmid37171860, year = {2023}, author = {Snaith, AE and Dunn, SJ and Moran, RA and Newton, PN and Dance, DAB and Davong, V and Kuenzli, E and Kantele, A and Corander, J and McNally, A}, title = {The highly diverse plasmid population found in Escherichia coli colonizing travellers to Laos and its role in antimicrobial resistance gene carriage.}, journal = {Microbial genomics}, volume = {9}, number = {5}, pages = {}, pmid = {37171860}, issn = {2057-5858}, support = {MRS0136601/MRC_/Medical Research Council/United Kingdom ; MR/S013660/1/MRC_/Medical Research Council/United Kingdom ; BBR0062611/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; /WT_/Wellcome Trust/United Kingdom ; 106698/Z/14/Z/WT_/Wellcome Trust/United Kingdom ; }, mesh = {Humans ; *Escherichia coli ; Anti-Bacterial Agents/pharmacology ; *Escherichia coli Infections/epidemiology ; Laos ; beta-Lactamases/genetics ; Drug Resistance, Bacterial/genetics ; Plasmids/genetics ; }, abstract = {Increased colonization by antimicrobial-resistant organisms is closely associated with international travel. This study investigated the diversity of mobile genetic elements involved with antimicrobial resistance (AMR) gene carriage in extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli that colonized travellers to Laos. Long-read sequencing was used to reconstruct complete plasmid sequences from 48 isolates obtained from the daily stool samples of 23 travellers over a 3 week period. This method revealed a collection of 105 distinct plasmids, 38.1 % (n=40) of which carried AMR genes. The plasmids in this population were diverse, mostly unreported and included 38 replicon types, with F-type plasmids (n=23) the most prevalent amongst those carrying AMR genes. Fine-scale analysis of all plasmids identified numerous AMR gene contexts and emphasized the importance of IS elements, specifically members of the IS6/IS26 family, in the evolution of complex multidrug resistance regions. We found a concerning convergence of ESBL and colistin resistance determinants, with three plasmids from two different F-type lineages carrying bla CTX-M and mcr genes. The extensive diversity seen here highlights the worrying probability that stable new vehicles for AMR will evolve in E. coli populations that can disseminate internationally through travel networks.}, }
@article {pmid37171266, year = {2023}, author = {Nagarajan, G and Govindan, R and Poomarimuthu, M and Andiappan, R and Elango, S and Maruthamuthu, S and Mariakuttikan, J and Kadiam, S}, title = {The microbiome and rheumatic heart disease: current knowledge and future perspectives.}, journal = {Acta cardiologica}, volume = {78}, number = {5}, pages = {525-533}, doi = {10.1080/00015385.2023.2207933}, pmid = {37171266}, issn = {1784-973X}, mesh = {Child ; Humans ; *Rheumatic Heart Disease ; Dysbiosis/complications ; *Streptococcal Infections ; Inflammation ; *Microbiota ; }, abstract = {Rheumatic heart disease (RHD) is a cardiovascular disease caused by an autoimmune response to group A Streptococcus (GAS) infection resulting in the damage of heart valves. RHD is the most commonly acquired heart disease among children and young adults with a global burden of over 40 million cases accounting for 306,000 deaths annually. Inflammation in the heart valves caused due to molecular mimicry between the GAS antigens and host cardiac proteins is facilitated by cytokines, cross-reactive antibodies and CD4[+] T cells. The complex interaction between genetic and environmental factors linked with erratic events leads to the loss of immunological tolerance and autoimmunity in RHD. Despite extensive research on the etiopathogenesis of RHD, the precise mechanism underpinning the initiation of acute rheumatic fever (ARF) to the progression of RHD still remains elusive. Mounting evidences support the contribution of the human microbiome in the development of several immune-mediated diseases including rheumatoid arthritis, juvenile idiopathic arthritis, Kawasaki disease, inflammatory bowel disease and type 1 diabetes. The microbiome and their metabolites could play a crucial role in the integrity of the epithelial barrier, development of the immune system, inflammation and differentiation of T cell subsets. Consequently, microbiome dysbiosis might result in autoimmunity by molecular mimicry, epitope spreading and bystander activation. This review discusses various aspects of the interaction between the microbiome and the immune system in order to reveal causative links relating dysbiosis and autoimmune diseases with special emphasis on RHD.}, }
@article {pmid37165188, year = {2023}, author = {Shalon, D and Culver, RN and Grembi, JA and Folz, J and Treit, PV and Shi, H and Rosenberger, FA and Dethlefsen, L and Meng, X and Yaffe, E and Aranda-Díaz, A and Geyer, PE and Mueller-Reif, JB and Spencer, S and Patterson, AD and Triadafilopoulos, G and Holmes, SP and Mann, M and Fiehn, O and Relman, DA and Huang, KC}, title = {Profiling the human intestinal environment under physiological conditions.}, journal = {Nature}, volume = {617}, number = {7961}, pages = {581-591}, pmid = {37165188}, issn = {1476-4687}, support = {R01 AI147023/AI/NIAID NIH HHS/United States ; RM1 GM135102/GM/NIGMS NIH HHS/United States ; T32 DK007056/DK/NIDDK NIH HHS/United States ; }, mesh = {Humans ; *Bile Acids and Salts/metabolism ; *Gastrointestinal Microbiome/physiology ; *Metabolome ; *Proteome/metabolism ; Bacteria/classification/isolation &amp; purification ; Bacteriophages/isolation &amp; purification/physiology ; Feces/chemistry/microbiology/virology ; *Intestines/chemistry/metabolism/microbiology/physiology/virology ; Digestion/physiology ; }, abstract = {The spatiotemporal structure of the human microbiome[1,2], proteome[3] and metabolome[4,5] reflects and determines regional intestinal physiology and may have implications for disease[6]. Yet, little is known about the distribution of microorganisms, their environment and their biochemical activity in the gut because of reliance on stool samples and limited access to only some regions of the gut using endoscopy in fasting or sedated individuals[7]. To address these deficiencies, we developed an ingestible device that collects samples from multiple regions of the human intestinal tract during normal digestion. Collection of 240 intestinal samples from 15 healthy individuals using the device and subsequent multi-omics analyses identified significant differences between bacteria, phages, host proteins and metabolites in the intestines versus stool. Certain microbial taxa were differentially enriched and prophage induction was more prevalent in the intestines than in stool. The host proteome and bile acid profiles varied along the intestines and were highly distinct from those of stool. Correlations between gradients in bile acid concentrations and microbial abundance predicted species that altered the bile acid pool through deconjugation. Furthermore, microbially conjugated bile acid concentrations exhibited amino acid-dependent trends that were not apparent in stool. Overall, non-invasive, longitudinal profiling of microorganisms, proteins and bile acids along the intestinal tract under physiological conditions can help elucidate the roles of the gut microbiome and metabolome in human physiology and disease.}, }
@article {pmid39076604, year = {2022}, author = {Qian, J and Wu, Z and Zhu, Y and Liu, C}, title = {One Health: a holistic approach for food safety in livestock.}, journal = {Science in One Health}, volume = {1}, number = {}, pages = {100015}, pmid = {39076604}, issn = {2949-7043}, abstract = {The food safety of livestock is a critical issue between animals and humans due to their complex interactions. Pathogens have the potential to spread at every stage of the animal food handling process, including breeding, processing, packaging, storage, transportation, marketing and consumption. In addition, application of the antibiotic usage in domestic animals is a controversial issue because, while they can combat food-borne zoonotic pathogens and promote animal growth and productivity, they can also lead to the transmission of antibiotic-resistant microorganisms and antibiotic-resistant genes across species and habitats. Coevolution of microbiomes may occur in humans and animals as well which may alter the structure of the human microbiome through animal food consumption. One Health is a holistic approach to systematically understand the complex relationships among humans, animals and environments which may provide effective countermeasures to solve food safety problems aforementioned. This paper depicts the main pathogen spectrum of livestock and animal products, summarizes the flow of antibiotic-resistant bacteria and genes between humans and livestock along the food-chain production, and the correlation of their microbiome is reviewed as well to advocate for deeper interdisciplinary communication and collaboration among researchers in medicine, epidemiology, veterinary medicine and ecology to promote One Health approaches to address the global food safety challenges.}, }
@article {pmid37163788, year = {2023}, author = {Seyedsayamdost, MR and Clardy, J}, title = {Discovering functional small molecules in the gut microbiome.}, journal = {Current opinion in chemical biology}, volume = {75}, number = {}, pages = {102309}, pmid = {37163788}, issn = {1879-0402}, support = {R01 AI172147/AI/NIAID NIH HHS/United States ; R01 AT009708/AT/NCCIH NIH HHS/United States ; R01 GM140034/GM/NIGMS NIH HHS/United States ; }, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Microbiota ; Bacteria/metabolism ; }, abstract = {The human microbiome has emerged as a source of bacterially produced, functional small molecules that help regulate health and disease, and their discovery and annotation has become a popular research topic. Identifying these molecules provides an essential step in unraveling the molecular mechanisms underlying biological outcomes. The relevance of specific bacterial members of the microbiome has been demonstrated in a variety of correlative studies, and there are many possible paths from these correlations to the responsible metabolites. Herein, we summarize two studies that have recently identified gut microbiome metabolites that modulate immune responses or promote physical activity. Aside from the deep insights gained, these studies provide blueprints for successfully uncovering the molecules and mechanisms that control important physiological pathways.}, }
@article {pmid37161031, year = {2023}, author = {Chmiel, JA and Stuivenberg, GA and Al, KF and Akouris, PP and Razvi, H and Burton, JP and Bjazevic, J}, title = {Vitamins as regulators of calcium-containing kidney stones - new perspectives on the role of the gut microbiome.}, journal = {Nature reviews. Urology}, volume = {20}, number = {10}, pages = {615-637}, pmid = {37161031}, issn = {1759-4820}, mesh = {Humans ; Vitamins/therapeutic use ; Calcium ; *Gastrointestinal Microbiome ; *Kidney Calculi ; *Urolithiasis ; Vitamin A ; Vitamin K ; }, abstract = {Calcium-based kidney stone disease is a highly prevalent and morbid condition, with an often complicated and multifactorial aetiology. An abundance of research on the role of specific vitamins (B6, C and D) in stone formation exists, but no consensus has been reached on how these vitamins influence stone disease. As a consequence of emerging research on the role of the gut microbiota in urolithiasis, previous notions on the contribution of these vitamins to urolithiasis are being reconsidered in the field, and investigation into previously overlooked vitamins (A, E and K) was expanded. Understanding how the microbiota influences host vitamin regulation could help to determine the role of vitamins in stone disease.}, }
@article {pmid37159872, year = {2023}, author = {Golob, JL}, title = {Human Microbiomes and Disease for the Biomedical Data Scientist.}, journal = {Annual review of biomedical data science}, volume = {6}, number = {}, pages = {259-273}, doi = {10.1146/annurev-biodatasci-020722-043017}, pmid = {37159872}, issn = {2574-3414}, mesh = {Humans ; *Microbiota ; Precision Medicine ; High-Throughput Nucleotide Sequencing/methods ; }, abstract = {The human microbiome is complex, variable from person to person, essential for health, and related to both the risk for disease and the efficacy of our treatments. There are robust techniques to describe microbiota with high-throughput sequencing, and there are hundreds of thousands of already-sequenced specimens in public archives. The promise remains to use the microbiome both as a prognostic factor and as a target for precision medicine. However, when used as an input in biomedical data science modeling, the microbiome presents unique challenges. Here, we review the most common techniques used to describe microbial communities, explore these unique challenges, and discuss the more successful approaches for biomedical data scientists seeking to use the microbiome as an input in their studies.}, }
@article {pmid37155564, year = {2023}, author = {Chernyaeva, L and Ratti, G and Teirilä, L and Fudo, S and Rankka, U and Pelkonen, A and Korhonen, P and Leskinen, K and Keskitalo, S and Salokas, K and Gkolfinopoulou, C and Crompton, KE and Javanainen, M and Happonen, L and Varjosalo, M and Malm, T and Leinonen, V and Chroni, A and Saavalainen, P and Meri, S and Kajander, T and Wollman, AJ and Nissilä, E and Haapasalo, K}, title = {Reduced binding of apoE4 to complement factor H promotes amyloid-β oligomerization and neuroinflammation.}, journal = {EMBO reports}, volume = {24}, number = {7}, pages = {e56467}, pmid = {37155564}, issn = {1469-3178}, support = {331108//Academy of Finland (AKA)/ ; 338160//Academy of Finland (AKA)/ ; 25022019//Jane and Aatos Erkko Foundation/ ; }, mesh = {Humans ; *Apolipoprotein E4/genetics/metabolism ; Complement Factor H/genetics ; *Alzheimer Disease/genetics/metabolism ; Neuroinflammatory Diseases ; Apolipoproteins E/chemistry/genetics/metabolism ; Amyloid beta-Peptides/metabolism ; Protein Isoforms/genetics/metabolism ; }, abstract = {The APOE4 variant of apolipoprotein E (apoE) is the most prevalent genetic risk allele associated with late-onset Alzheimer's disease (AD). ApoE interacts with complement regulator factor H (FH), but the role of this interaction in AD pathogenesis is unknown. Here we elucidate the mechanism by which isoform-specific binding of apoE to FH alters Aβ1-42-mediated neurotoxicity and clearance. Flow cytometry and transcriptomic analysis reveal that apoE and FH reduce binding of Aβ1-42 to complement receptor 3 (CR3) and subsequent phagocytosis by microglia which alters expression of genes involved in AD. Moreover, FH forms complement-resistant oligomers with apoE/Aβ1-42 complexes and the formation of these complexes is isoform specific with apoE2 and apoE3 showing higher affinity to FH than apoE4. These FH/apoE complexes reduce Aβ1-42 oligomerization and toxicity, and colocalize with complement activator C1q deposited on Aβ plaques in the brain. These findings provide an important mechanistic insight into AD pathogenesis and explain how the strongest genetic risk factor for AD predisposes for neuroinflammation in the early stages of the disease pathology.}, }
@article {pmid37154305, year = {2023}, author = {Zou, D and Dong, Y and Chen, J}, title = {[Live biotherapeutic products: the forefront of innovative drug development driven by biotechnology].}, journal = {Sheng wu gong cheng xue bao = Chinese journal of biotechnology}, volume = {39}, number = {4}, pages = {1275-1289}, doi = {10.13345/j.cjb.220669}, pmid = {37154305}, issn = {1872-2075}, mesh = {Humans ; *Probiotics ; Dietary Supplements ; Bacteria ; Drug Development ; Biotechnology ; }, abstract = {As human microbiome research advances, a large body of evidence shows that microorganisms are closely related to human health. Probiotics were discovered and used as foods or dietary supplements with health benefits in the last century. Microorganisms have shown broader application prospects in human health since the turn of the century, owing to the rapid development of technologies such as microbiome analysis, DNA synthesis and sequencing, and gene editing. In recent years, the concept of "next-generation probiotics" has been proposed as new drugs, and microorganisms are considered as "live biotherapeutic products (LBP)". In a nutshell, LBP is a living bacterial drug that can be used to prevent or treat certain human diseases and indications. Because of its distinct advantages, LBP has risen to the forefront of drug development research and has very broad development prospects. This review introduces the varieties and research advances on LBP from a biotechnology standpoint, followed by summarizing the challenges and opportunities for LBP clinical implementations, with the aim to facilitate LBP development.}, }
@article {pmid37146137, year = {2023}, author = {Lietzan, AD and Simpson, JB and Walton, WG and Jariwala, PB and Xu, Y and Boynton, MH and Liu, J and Redinbo, MR}, title = {Microbial β-glucuronidases drive human periodontal disease etiology.}, journal = {Science advances}, volume = {9}, number = {18}, pages = {eadg3390}, pmid = {37146137}, issn = {2375-2548}, support = {R01 GM135218/GM/NIGMS NIH HHS/United States ; UM1 TR004406/TR/NCATS NIH HHS/United States ; P30 CA016086/CA/NCI NIH HHS/United States ; UL1 TR002489/TR/NCATS NIH HHS/United States ; R01 GM137286/GM/NIGMS NIH HHS/United States ; }, mesh = {Humans ; Glucuronidase/metabolism ; *Gastrointestinal Microbiome/physiology ; *Periodontal Diseases/etiology ; *Microbiota ; *Periodontitis/microbiology ; Enzyme Inhibitors/pharmacology ; }, abstract = {Periodontitis is a chronic inflammatory disease associated with persistent oral microbial dysbiosis. The human β-glucuronidase (GUS) degrades constituents of the periodontium and is used as a biomarker for periodontitis severity. However, the human microbiome also encodes GUS enzymes, and the role of these factors in periodontal disease is poorly understood. Here, we define the 53 unique GUSs in the human oral microbiome and examine diverse GUS orthologs from periodontitis-associated pathogens. Oral bacterial GUS enzymes are more efficient polysaccharide degraders and processers of biomarker substrates than the human enzyme, particularly at pHs associated with disease progression. Using a microbial GUS-selective inhibitor, we show that GUS activity is reduced in clinical samples obtained from individuals with untreated periodontitis and that the degree of inhibition correlates with disease severity. Together, these results establish oral GUS activity as a biomarker that captures both host and microbial contributions to periodontitis, facilitating more efficient clinical monitoring and treatment paradigms for this common inflammatory disease.}, }
@article {pmid37144511, year = {2023}, author = {Xia, B and Wang, J and Zhang, D and Hu, X}, title = {The human microbiome links to prostate cancer risk and treatment (Review).}, journal = {Oncology reports}, volume = {49}, number = {6}, pages = {}, pmid = {37144511}, issn = {1791-2431}, mesh = {Male ; Humans ; *Prostatic Neoplasms/therapy ; Androgen Antagonists ; *Microbiota/physiology ; }, abstract = {Prostate cancer (Pca) is the second most common cancer type worldwide. Microorganisms colonized in different body parts may affect the development/progression and treatment of Pca through direct or indirect interactions. The composition of microorganisms in different colonization sites and their effects on Pca may differ. In recent years, several studies have focused on the differences in the microbiota of patients with Pca, and dysbiosis may affect the inflammatory status, hormone levels and microbial metabolites leading to Pca progression. However, little is known about the interaction between Pca treatment and microorganisms; for example, how androgen deprivation therapy and androgen receptor axis‑targeting therapeutics for Pca affect microbiota composition and metabolism, and how the microbiota affects treatment response in patients with Pca remain to be understood. The present review explored the current studies on the relevance of microbiota to Pca progression and treatment to provide direction for future microbiome‑Pca research. Due to the complexity of the potential interconnections between Pca and the microbiota, further investigation is critical.}, }
@article {pmid37139495, year = {2023}, author = {Gao, J and Zhao, L and Cheng, Y and Lei, W and Wang, Y and Liu, X and Zheng, N and Shao, L and Chen, X and Sun, Y and Ling, Z and Xu, W}, title = {Probiotics for the treatment of depression and its comorbidities: A systemic review.}, journal = {Frontiers in cellular and infection microbiology}, volume = {13}, number = {}, pages = {1167116}, pmid = {37139495}, issn = {2235-2988}, mesh = {Animals ; Humans ; Brain ; Depression/therapy ; Dysbiosis/therapy ; *Gastrointestinal Microbiome/physiology ; *Mental Disorders ; *Probiotics/therapeutic use ; }, abstract = {Depression is one of the most common psychiatric conditions, characterized by significant and persistent depressed mood and diminished interest, and often coexists with various comorbidities. The underlying mechanism of depression remain elusive, evidenced by the lack of an appreciate therapy. Recent abundant clinical trials and animal studies support the new notion that the gut microbiota has emerged as a novel actor in the pathophysiology of depression, which partakes in bidirectional communication between the gut and the brain through the neuroendocrine, nervous, and immune signaling pathways, collectively known as the microbiota-gut-brain (MGB) axis. Alterations in the gut microbiota can trigger the changes in neurotransmitters, neuroinflammation, and behaviors. With the transition of human microbiome research from studying associations to investigating mechanistic causality, the MGB axis has emerged as a novel therapeutic target in depression and its comorbidities. These novel insights have fueled idea that targeting on the gut microbiota may open new windows for efficient treatment of depression and its comorbidities. Probiotics, live beneficial microorganisms, can be used to modulate gut dysbiosis into a new eubiosis and modify the occurrence and development of depression and its comorbidities. In present review, we summarize recent findings regarding the MGB axis in depression and discuss the potential therapeutic effects of probiotics on depression and its comorbidities.}, }
@article {pmid37138077, year = {2023}, author = {Bayfield, OW and Shkoporov, AN and Yutin, N and Khokhlova, EV and Smith, JLR and Hawkins, DEDP and Koonin, EV and Hill, C and Antson, AA}, title = {Structural atlas of a human gut crassvirus.}, journal = {Nature}, volume = {617}, number = {7960}, pages = {409-416}, pmid = {37138077}, issn = {1476-4687}, support = {/WT_/Wellcome Trust/United Kingdom ; R01 GM129325/GM/NIGMS NIH HHS/United States ; /LM/NLM NIH HHS/United States ; /AI/NIAID NIH HHS/United States ; }, mesh = {Bacteroides ; Capsid/chemistry/metabolism/ultrastructure ; Protein Unfolding ; Humans ; *Virion/chemistry/metabolism/ultrastructure ; *DNA Viruses/classification/chemistry/isolation &amp; purification/ultrastructure/metabolism ; *Viral Proteins/chemistry/metabolism/ultrastructure ; *Intestines/microbiology/virology ; Protein Folding ; Cryoelectron Microscopy ; Virus Assembly ; }, abstract = {CrAssphage and related viruses of the order Crassvirales (hereafter referred to as crassviruses) were originally discovered by cross-assembly of metagenomic sequences. They are the most abundant viruses in the human gut, are found in the majority of individual gut viromes, and account for up to 95% of the viral sequences in some individuals[1-4]. Crassviruses are likely to have major roles in shaping the composition and functionality of the human microbiome, but the structures and roles of most of the virally encoded proteins are unknown, with only generic predictions resulting from bioinformatic analyses[4,5]. Here we present a cryo-electron microscopy reconstruction of Bacteroides intestinalis virus ΦcrAss001[6], providing the structural basis for the functional assignment of most of its virion proteins. The muzzle protein forms an assembly about 1 MDa in size at the end of the tail and exhibits a previously unknown fold that we designate the 'crass fold', that is likely to serve as a gatekeeper that controls the ejection of cargos. In addition to packing the approximately 103 kb of virus DNA, the ΦcrAss001 virion has extensive storage space for virally encoded cargo proteins in the capsid and, unusually, within the tail. One of the cargo proteins is present in both the capsid and the tail, suggesting a general mechanism for protein ejection, which involves partial unfolding of proteins during their extrusion through the tail. These findings provide a structural basis for understanding the mechanisms of assembly and infection of these highly abundant crassviruses.}, }
@article {pmid37132117, year = {2023}, author = {Gong, J and Liu, S and Wang, S and Ruan, H and Mou, Q and Fan, P and Chen, T and Cai, W and Lu, Y and Lu, Z}, title = {Identification of fecal microbiome signatures associated with familial longevity and candidate metabolites for healthy aging.}, journal = {Aging cell}, volume = {22}, number = {6}, pages = {e13848}, pmid = {37132117}, issn = {1474-9726}, mesh = {Humans ; *Healthy Aging/genetics ; RNA, Ribosomal, 16S/genetics ; Longevity/genetics ; *Microbiota ; Aging/genetics ; Metabolomics ; }, abstract = {Gut microbiota associated with longevity plays an important role in the adaptation to damaging stimuli accumulated during the aging process. The mechanism by which the longevity-associated microbiota protects the senescent host remains unclear, while the metabolites of the gut bacteria are of particular interest. Here, an integrated analysis of untargeted metabolomics and 16S rRNA gene sequencing was used to characterize the metabolite and microbiota profiles of long-lived individuals (aged ≥90 years) in comparison to old-elderly (aged 75-89 years), young-elderly (aged 60-74 years), and young to middle-aged (aged ≤59 years) individuals. This novel study constructed both metabolite and microbiota trajectories across aging in populations from Jiaoling county (the seventh longevity town of the world) in China. We found that the long-lived group exhibited remarkably differential metabolomic signatures, highlighting the existence of metabolic heterogeneity with aging. Importantly, we also discovered that long-lived individuals from the familial longevity cohort harbored a microbiome distinguished from that of the general population. Specifically, we identified that the levels of a candidate metabolite, pinane thromboxane A2 (PTA2), which is positively associated with aging, were consistently higher in individuals with familial longevity and their younger descendants than in those of the general population. Furtherly, functional analysis revealed that PTA2 potentiated the efficiency of microglial phagocytosis of β-amyloid 40 and enhanced an anti-inflammatory phenotype, indicating a protective role of PTA2 toward host health. Collectively, our results improve the understanding of the role of the gut microbiome in longevity and may facilitate the development of strategies for healthy aging.}, }
@article {pmid37129834, year = {2023}, author = {Duarte, MJ and Tien, PC and Somsouk, M and Price, JC}, title = {The human microbiome and gut-liver axis in people living with HIV.}, journal = {Current HIV/AIDS reports}, volume = {20}, number = {3}, pages = {170-180}, pmid = {37129834}, issn = {1548-3576}, support = {U01 HL146242/NH/NIH HHS/United States ; K24 AI108516/NH/NIH HHS/United States ; R01DK123746/NH/NIH HHS/United States ; T32 DK060414/DK/NIDDK NIH HHS/United States ; R01 DK109823/NH/NIH HHS/United States ; T32 DK060414/NH/NIH HHS/United States ; }, mesh = {Humans ; Dysbiosis ; *HIV Infections/complications ; Liver ; *Microbiota ; *Gastrointestinal Microbiome ; }, abstract = {PURPOSE OF REVIEW: Chronic liver disease is a major cause of morbidity and mortality amongst people living with HIV (PLWH). Emerging data suggests that gut microbial translocation may play a role in driving and modulating liver disease, a bi-directional relationship termed the gut-liver axis. While it is recognized that PLWH have a high degree of dysbiosis and gut microbial translocation, little is known about the gut-liver axis in PLWH.<br><br>RECENT FINDINGS: Recent studies have shown that microbial translocation can directly lead to hepatic inflammation, and have linked gut microbial signatures, dysbiosis, and translocation to liver disease in PLWH. Additionally, multiple trials have explored interventions targeting the microbiome in PLWH. Emerging research supports the interaction between the gut microbiome and liver disease in PLWH. This offers new opportunities to expand our understanding of the pathophysiology of liver disease in this population, as well as to explore possible clinical interventions.}, }
@article {pmid37127667, year = {2023}, author = {Nearing, JT and DeClercq, V and Langille, MGI}, title = {Investigating the oral microbiome in retrospective and prospective cases of prostate, colon, and breast cancer.}, journal = {NPJ biofilms and microbiomes}, volume = {9}, number = {1}, pages = {23}, pmid = {37127667}, issn = {2055-5008}, mesh = {Male ; Humans ; *Breast Neoplasms ; Retrospective Studies ; Prostate ; RNA, Ribosomal, 16S/genetics ; *Microbiota/genetics ; *Prostatic Neoplasms ; *Colonic Neoplasms ; }, abstract = {The human microbiome has been proposed as a potentially useful biomarker for several cancers. To examine this, we made use of salivary samples from the Atlantic Partnership for Tomorrow's Health (PATH) project and Alberta's Tomorrow Project (ATP). Sample selection was divided into both a retrospective and prospective case control design examining prostate, breast, and colon cancer. In total 89 retrospective and 260 prospective cancer cases were matched to non-cancer controls and saliva samples were sequenced using 16S rRNA gene sequencing. We found no significant differences in alpha diversity. All beta diversity measures were insignificant except for unweighted UniFrac profiles in retrospective breast cancer cases and weighted UniFrac, Bray-Curtis and Robust Atchinson's distances in colon cancer after testing with age and sex adjusted MiRKAT models. Differential abundance (DA) analysis showed several taxa that were associated with previous cancer in all three groupings. Only one genus (Clostridia UCG-014) in breast cancer and one ASV (Fusobacterium periodonticum) in colon cancer was identified by more than one DA tool. In prospective cases three ASVs were associated with colon cancer, one ASV with breast cancer, and one ASV with prostate cancer. Random Forest classification showed low levels of signal in both study designs in breast and prostate cancer. Contrastingly, colon cancer did show signal in our retrospective analysis (AUC: 0.737) and in one of two prospective cohorts (AUC: 0.717). Our results indicate that it is unlikely that reliable microbial oral biomarkers for breast and prostate cancer exist.. However, further research into the oral microbiome and colon cancer could be fruitful.}, }
@article {pmid37122947, year = {2023}, author = {Sinkko, H and Lehtimäki, J and Lohi, H and Ruokolainen, L and Hielm-Björkman, A}, title = {Distinct healthy and atopic canine gut microbiota is influenced by diet and antibiotics.}, journal = {Royal Society open science}, volume = {10}, number = {4}, pages = {221104}, pmid = {37122947}, issn = {2054-5703}, abstract = {The rising trend in non-communicable chronic inflammatory diseases coincides with changes in Western lifestyle. While changes in the human microbiota may play a central role in the development of chronic diseases, estimating the contribution of associated lifestyle factors remains challenging. We studied the influence of lifestyle-diet, antibiotic use, and residential environment with housing and family-on the gut microbiota of healthy and owner-reported atopic pet dogs, searching for associations between the lifestyle factors, atopy and microbiota. The results showed that atopic and healthy dogs had contrasting gut microbial composition. The gut microbiota also differed between two breeds, Labrador Retriever and Finnish Lapphund, selected for our study. Among all lifestyle factors studied, diet was most significantly associated with gut microbiota but only weakly with atopic symptoms. Thus, diet- and atopy-associated changes in the microbiota were not interrelated. Instead, the severity of symptoms was positively associated with the usage of antibiotics, which in turn was associated with the microbiota composition. Urban lifestyle was significantly associated with the increased prevalence of allergies but not with the gut microbiota. Our results from pet dogs supported previous evidence from humans, demonstrating that antibiotics, gut microbiota and atopic manifestation are interrelated. This congruence suggests that canine atopy might be a promising model for understanding the aetiology of human allergy.}, }
@article {pmid37122075, year = {2023}, author = {Simpson, JB and Sekela, JJ and Carry, BS and Beaty, V and Patel, S and Redinbo, MR}, title = {Diverse but desolate landscape of gut microbial azoreductases: A rationale for idiopathic IBD drug response.}, journal = {Gut microbes}, volume = {15}, number = {1}, pages = {2203963}, pmid = {37122075}, issn = {1949-0984}, support = {P30 CA016086/CA/NCI NIH HHS/United States ; R01 GM135218/GM/NIGMS NIH HHS/United States ; R01 GM137286/GM/NIGMS NIH HHS/United States ; }, mesh = {Humans ; *Gastrointestinal Microbiome ; *Prodrugs ; *Amlodipine Besylate, Olmesartan Medoxomil Drug Combination ; *Crohn Disease ; *Colitis, Ulcerative ; Mesalamine/therapeutic use ; *Inflammatory Bowel Diseases/drug therapy ; }, abstract = {Prodrugs reliant on microbial activation are widely used but exhibit a range of efficacies that remain poorly understood. The anti-inflammatory compound 5-aminosalicylic acid (5-ASA), which is packaged in a variety of azo-linked prodrugs provided to most Ulcerative Colitis (UC) patients, shows confounding inter-individual variabilities in response. Such prodrugs must be activated by azo-bond reduction to form 5-ASA, a process that has been attributed to both enzymatic and non-enzymatic catalysis. Gut microbial azoreductases (AzoRs) are the first catalysts shown to activate azo-linked drugs and to metabolize toxic azo-chemicals. Here, we chart the scope of the structural and functional diversity of AzoRs in health and in patients with the inflammatory bowel diseases (IBDs) UC and Crohn's Disease (CD). Using structural metagenomics, we define the landscape of gut microbial AzoRs in 413 healthy donor and 1059 IBD patient fecal samples. Firmicutes encode a significantly higher number of unique AzoRs compared to other phyla. However, structural and biochemical analyses of distinct AzoRs from the human microbiome reveal significant differences between prevalent orthologs in the processing of toxic azo-dyes, and their generally poor activation of IBD prodrugs. Furthermore, while individuals with IBD show higher abundances of AzoR-encoding gut microbial taxa than healthy controls, the overall abundance of AzoR-encoding microbes is markedly low in both disease and health. Together, these results establish that gut microbial AzoRs are functionally diverse but sparse in both health and disease, factors that may contribute to non-optimal processing of azo-linked prodrugs and idiopathic IBD drug responses.}, }
@article {pmid37120981, year = {2023}, author = {De Alcaraz-Fossoul, J and Wang, Y and Liu, R and Mancenido, M and Marshall, PA and Núñez, C and Broatch, J and Ferry, L}, title = {Microbes in fingerprints: A source for dating crime evidence?.}, journal = {Forensic science international. Genetics}, volume = {65}, number = {}, pages = {102883}, doi = {10.1016/j.fsigen.2023.102883}, pmid = {37120981}, issn = {1878-0326}, mesh = {Humans ; Aged ; *Microbiota ; Touch ; Crime ; Forensic Sciences ; Dermatoglyphics ; }, abstract = {Interest in the human microbiome has grown in recent years because of increasing applications to biomedicine and forensic science. However, the potential for dating evidence at a crime scene based upon time-dependent changes in microbial signatures has not been established, despite a relatively straightforward scientific process for isolating the microbiome. We hypothesize that modifications in microbial diversity, abundance, and succession can provide estimates of the time a surface was touched for investigative purposes. In this proof-of-concept research, the sequencing and analysis of the 16 S rRNA gene from microbes present in fresh and aged latent fingerprints deposited by three donors with pre- and post-washed hands is reported. The stability of major microbial phyla is confirmed while the dynamics of less abundant groups is described up to 21 days post-deposition. Most importantly, a phylum is suggested as the source for possible biological markers to date fingerprints: Deinococcus-Thermus.}, }
@article {pmid37119938, year = {2023}, author = {Luqman, A}, title = {The orchestra of human bacteriome by hormones.}, journal = {Microbial pathogenesis}, volume = {180}, number = {}, pages = {106125}, doi = {10.1016/j.micpath.2023.106125}, pmid = {37119938}, issn = {1096-1208}, mesh = {Humans ; *Norepinephrine/pharmacology ; *Epinephrine/pharmacology ; Bacteria/metabolism ; Quorum Sensing ; Hormones ; }, abstract = {Human microbiome interact reciprocally with the host. Recent findings showed the capability of microorganisms to response towards host signaling molecules, such as hormones. Studies confirmed the complex response of bacteria in response to hormones exposure. These hormones impact many aspects on bacteria, such as the growth, metabolism, and virulence. The effects of each hormone seem to be species-specific. The most studied hormones are cathecolamines also known as stress hormones that consists of epinephrine, norepinephrine and dopamine. These hormones affect the growth of bacteria either inhibit or enhance by acting like a siderophore. Epinephrine and norepinephrine have also been reported to activate QseBC, a quorum sensing in Gram-negative bacteria and eventually enhances the virulence of pathogens. Other hormones were also reported to play a role in shaping human microbiome composition and affect their behavior. Considering the complex response of bacteria on hormones, it highlights the necessity to take the impact of hormones on bacteria into account in studying human health in relation to human microbiome.}, }
@article {pmid37116481, year = {2023}, author = {Manara, S and Selma-Royo, M and Huang, KD and Asnicar, F and Armanini, F and Blanco-Miguez, A and Cumbo, F and Golzato, D and Manghi, P and Pinto, F and Valles-Colomer, M and Amoroso, L and Corrias, MV and Ponzoni, M and Raffaetà, R and Cabrera-Rubio, R and Olcina, M and Pasolli, E and Collado, MC and Segata, N}, title = {Maternal and food microbial sources shape the infant microbiome of a rural Ethiopian population.}, journal = {Current biology : CB}, volume = {33}, number = {10}, pages = {1939-1950.e4}, pmid = {37116481}, issn = {1879-0445}, support = {R01 CA230551/CA/NCI NIH HHS/United States ; U01 CA230551/CA/NCI NIH HHS/United States ; }, mesh = {Female ; Humans ; Infant ; Infant, Newborn ; *Microbiota ; Bacteria ; Milk, Human/microbiology ; Mothers ; *Gastrointestinal Microbiome ; Feces/microbiology ; }, abstract = {The human microbiome seeding starts at birth, when pioneer microbes are acquired mainly from the mother. Mode of delivery, antibiotic prophylaxis, and feeding method have been studied as modulators of mother-to-infant microbiome transmission, but other key influencing factors like modern westernized lifestyles with high hygienization, high-calorie diets, and urban settings, compared with non-westernized lifestyles have not been investigated yet. In this study, we explored the mother-infant sharing of characterized and uncharacterized microbiome members via strain-resolved metagenomics in a cohort of Ethiopian mothers and infants, and we compared them with four other cohorts with different lifestyles. The westernized and non-westernized newborns' microbiomes composition overlapped during the first months of life more than later in life, likely reflecting similar initial breast-milk-based diets. Ethiopian and other non-westernized infants shared a smaller fraction of the microbiome with their mothers than did most westernized populations, despite showing a higher microbiome diversity, and uncharacterized species represented a substantial fraction of those shared in the Ethiopian cohort. Moreover, we identified uncharacterized species belonging to the Selenomonadaceae and Prevotellaceae families specifically present and shared only in the Ethiopian cohort, and we showed that a locally produced fermented food, injera, can contribute to the higher diversity observed in the Ethiopian infants' gut with bacteria that are not part of the human microbiome but are acquired through fermented food consumption. Taken together, these findings highlight the fact that lifestyle can impact the gut microbiome composition not only through differences in diet, drug consumption, and environmental factors but also through its effect on mother-infant strain-sharing patterns.}, }
@article {pmid37110440, year = {2023}, author = {Efremova, I and Maslennikov, R and Alieva, A and Poluektova, E and Ivashkin, V}, title = {Small Intestinal Bacterial Overgrowth Is Associated with Poor Prognosis in Cirrhosis.}, journal = {Microorganisms}, volume = {11}, number = {4}, pages = {}, pmid = {37110440}, issn = {2076-2607}, abstract = {BACKGROUND: Small intestinal bacterial overgrowth (SIBO) is associated with numerous manifestations of cirrhosis. To determine whether the presence of SIBO affects the prognosis in cirrhosis was the aim of the study.<br><br>METHODS: This prospective cohort study included 50 patients. All participants underwent a lactulose hydrogen breath test for SIBO. The follow-up period was 4 years.<br><br>RESULTS: SIBO was detected in 26 (52.0%) patients: in 10 (52.6%) patients with compensated cirrhosis and in 16 (51.6%) ones with decompensated cirrhosis. Twelve (46.2%) patients with SIBO and four (16.7%) patients without SIBO died within 4 years (p = 0.009). Among patients with decompensated cirrhosis, 8 (50.0%) patients with SIBO and 3 (20.0%) patients without SIBO died (p = 0.027). Among patients with compensated cirrhosis, four (40.0%) patients with SIBO and one (11.1%) patient without SIBO died (p = 0.045). Among patients with SIBO, there was no difference in mortality between patients with compensated and decompensated cirrhosis (p = 0.209). It was the same for patients without SIBO (p = 0.215). SIBO affects the prognosis only in the first year of follow-up in decompensated cirrhosis, and only in subsequent years in compensated cirrhosis. Presence of SIBO (p = 0.028; HR = 4.2(1.2-14.9)) and serum albumin level (p = 0.027) were significant independent risk factors for death in cirrhosis.<br><br>CONCLUSIONS: SIBO is associated with poor prognosis in cirrhosis.}, }
@article {pmid37108423, year = {2023}, author = {Kunika,  and Frey, N and Rangrez, AY}, title = {Exploring the Involvement of Gut Microbiota in Cancer Therapy-Induced Cardiotoxicity.}, journal = {International journal of molecular sciences}, volume = {24}, number = {8}, pages = {}, pmid = {37108423}, issn = {1422-0067}, support = {RA 2717/4-1 and FR 1289/17-1//Deutsche Forschungsgemeinschaft/ ; }, mesh = {Humans ; *Gastrointestinal Microbiome ; Cardiotoxicity/etiology ; *Microbiota ; Intestines/microbiology ; *Neoplasms/drug therapy ; Bacteria ; Dysbiosis/chemically induced ; }, abstract = {Trillions of microbes in the human intestinal tract, including bacteria, viruses, fungi, and protozoa, are collectively referred to as the gut microbiome. Recent technological developments have led to a significant increase in our understanding of the human microbiome. It has been discovered that the microbiome affects both health and the progression of diseases, including cancer and heart disease. Several studies have indicated that the gut microbiota may serve as a potential target in cancer therapy modulation, by enhancing the effectiveness of chemotherapy and/or immunotherapy. Moreover, altered microbiome composition has been linked to the long-term effects of cancer therapy; for example, the deleterious effects of chemotherapy on microbial diversity can, in turn, lead to acute dysbiosis and serious gastrointestinal toxicity. Specifically, the relationship between the microbiome and cardiac diseases in cancer patients following therapy is poorly understood. In this article, we provide a summary of the role of the microbiome in cancer treatment, while also speculating on a potential connection between treatment-related microbial changes and cardiotoxicity. Through a brief review of the literature, we further explore which bacterial families or genera were differentially affected in cancer treatment and cardiac disease. A deeper understanding of the link between the gut microbiome and cardiotoxicity caused by cancer treatment may help lower the risk of this critical and potentially fatal side effect.}, }
@article {pmid37107220, year = {2023}, author = {Vacca, M and Pinto, D and Annunziato, A and Ressa, A and Calasso, M and Pontonio, E and Celano, G and De Angelis, M}, title = {Gluten-Free Bread Enriched with Artichoke Leaf Extract In Vitro Exerted Antioxidant and Anti-Inflammatory Properties.}, journal = {Antioxidants (Basel, Switzerland)}, volume = {12}, number = {4}, pages = {}, pmid = {37107220}, issn = {2076-3921}, abstract = {Due to its high nutritional value and broad beneficial effects, the artichoke plant (Cynara cardunculus L.) is an excellent healthy food candidate. Additionally, the artichoke by-products are usually discarded even though they still contain a huge concentration of dietary fibers, phenolic acids, and other micronutrients. The present work aimed to characterize a laboratory-made gluten-free bread (B) using rice flour supplemented with a powdered extract from artichoke leaves (AEs). The AE, accounting for the 5% of titratable chlorogenic acid, was added to the experimental gluten-free bread. Accounting for different combinations, four different bread batches were prepared. To evaluate the differences, a gluten-free type-II sourdough (tII-SD) was added in two doughs (SB and SB-AE), while the related controls (YB and YB-AE) did not contain the tII-SD. Profiling the digested bread samples, SB showed the lowest glycemic index, while SB-AE showed the highest antioxidant properties. The digested samples were also fermented in fecal batches containing viable cells from fecal microbiota samples obtained from healthy donors. Based on plate counts, no clear tendencies emerged concerning the analyzed microbial patterns; by contrast, when profiling volatile organic compounds, significant differences were observed in SB-AE, exhibiting the highest scores of hydrocinnamic and cyclohexanecarboxylic acids. The fecal fermented supernatants were recovered and assayed for healthy properties on human keratinocyte cell lines against oxidative stress and for effectiveness in modulating the expression of proinflammatory cytokines in Caco-2 cells. While the first assay emphasized the contribution of AE to protect against stressor agents, the latter enlightened how the combination of SB with AE decreased the cellular TNF-α and IL1-β expression. In conclusion, this preliminary study suggests that the combination of AE with sourdough biotechnology could be a promising tool to increase the nutritional and healthy features of gluten-free bread.}, }
@article {pmid37106510, year = {2023}, author = {Luo, X and Li, H and Fan, X and Wu, X and Zhou, R and Lei, Y and Xue, D and Yang, F and Xu, Y and Wang, K}, title = {The Gut Microbiota-Brain Axis: Potential Mechanism of Drug Addiction.}, journal = {Current topics in medicinal chemistry}, volume = {23}, number = {18}, pages = {1782-1792}, doi = {10.2174/1568026623666230418114133}, pmid = {37106510}, issn = {1873-4294}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; Brain-Gut Axis ; *Microbiota ; Brain/metabolism ; *Nervous System Diseases/metabolism ; *Substance-Related Disorders ; }, abstract = {As a chronic encephalopathy, drug addiction is responsible for millions of deaths per year around the world. The gut microbiome is a crucial component of the human microbiome. Through dynamic bidirectional communication along the 'gut-brain axis,' gut bacteria cooperate with their hosts to regulate the development and function of the immune, metabolic, and nervous systems. These processes may affect human health because some brain diseases are related to the composition of gut bacteria, and disruptions in microbial communities have been implicated in neurological disorders. We review the compositional and functional diversity of the gut microbiome in drug addiction. We discuss intricate and crucial connections between the gut microbiota and the brain involving multiple biological systems and possible contributions by the gut microbiota to neurological disorders. Finally, the treatment of probiotics and fecal transplantation was summarized. This was done to further understand the role of intestinal microecology in the pathogenesis of drug addiction and to explore new methods for the treatment of drug addiction.}, }
@article {pmid37102387, year = {2023}, author = {Lukkarinen, M and Kirjavainen, PV and Backman, K and Gonzales-Inca, C and Hickman, B and Kallio, S and Karlsson, H and Karlsson, L and Keski-Nisula, L and Korhonen, LS and Korpela, K and Kuitunen, M and Kukkonen, AK and Käyhkö, N and Lagström, H and Lukkarinen, H and Peltola, V and Pentti, J and Salonen, A and Savilahti, E and Tuoresmäki, P and Täubel, M and Vahtera, J and de Vos, WM and Pekkanen, J and Karvonen, AM}, title = {Early-life environment and the risk of eczema at 2 years-Meta-analyses of six Finnish birth cohorts.}, journal = {Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology}, volume = {34}, number = {4}, pages = {e13945}, doi = {10.1111/pai.13945}, pmid = {37102387}, issn = {1399-3038}, mesh = {Child ; Infant, Newborn ; Female ; Humans ; Child, Preschool ; Birth Cohort ; Finland/epidemiology ; *Eczema/epidemiology ; *Hypersensitivity/epidemiology ; Seasons ; }, abstract = {BACKGROUND: Urban-related nature exposures are suggested to contribute to the rising prevalence of allergic diseases despite little supporting evidence. Our aim was to evaluate the impact of 12 land cover classes and two greenness indices around homes at birth on the development of doctor-diagnosed eczema by the age of 2 years, and the influence of birth season.<br><br>METHODS: Data from 5085 children were obtained from six Finnish birth cohorts. Exposures were provided by the Coordination of Information on the Environment in three predefined grid sizes. Adjusted logistic regression was run in each cohort, and pooled effects across cohorts were estimated using fixed or random effect meta-analyses.<br><br>RESULTS: In meta-analyses, neither greenness indices (NDVI or VCDI, 250&#x2009;m&#x2009;&#xd7;&#x2009;250&#x2009;m grid size) nor residential or industrial/commercial areas were associated with eczema by age of 2&#x2009;years. Coniferous forest (adjusted odds ratio 1.19; 95% confidence interval 1.01-1.39 for the middle and 1.16; 0.98-1.28 for the highest vs. lowest tertile) and mixed forest (1.21; 1.02-1.42 middle vs. lowest tertile) were associated with elevated eczema risk. Higher coverage with agricultural areas tended to associate with elevated eczema risk (1.20; 0.98-1.48 vs. none). In contrast, transport infrastructure was inversely associated with eczema (0.77; 0.65-0.91 highest vs. lowest tertile).<br><br>CONCLUSION: Greenness around the home during early childhood does not seem to protect from eczema. In contrast, nearby coniferous and mixed forests may increase eczema risk, as well as being born in spring close to forest or high-green areas.}, }
@article {pmid37101246, year = {2023}, author = {Zhang, D and Zhang, J and Kalimuthu, S and Liu, J and Song, ZM and He, BB and Cai, P and Zhong, Z and Feng, C and Neelakantan, P and Li, YX}, title = {A systematically biosynthetic investigation of lactic acid bacteria reveals diverse antagonistic bacteriocins that potentially shape the human microbiome.}, journal = {Microbiome}, volume = {11}, number = {1}, pages = {91}, pmid = {37101246}, issn = {2049-2618}, mesh = {Female ; Humans ; *Bacteriocins/genetics ; *Lactobacillales/genetics ; *Microbiota/genetics ; Metagenome ; Anti-Bacterial Agents/pharmacology ; }, abstract = {BACKGROUND: Lactic acid bacteria (LAB) produce various bioactive secondary metabolites (SMs), which endow LAB with a protective role for the host. However, the biosynthetic potentials of LAB-derived SMs remain elusive, particularly in their diversity, abundance, and distribution in the human microbiome. Thus, it is still unknown to what extent LAB-derived SMs are involved in microbiome homeostasis.<br><br>RESULTS: Here, we systematically investigate the biosynthetic potential of LAB from 31,977 LAB genomes, identifying 130,051 secondary metabolite biosynthetic gene clusters (BGCs) of 2,849 gene cluster families (GCFs). Most of these GCFs are species-specific or even strain-specific and uncharacterized yet. Analyzing 748 human-associated metagenomes, we gain an insight into the profile of LAB BGCs, which are highly diverse and niche-specific in the human microbiome. We discover that most LAB BGCs may encode bacteriocins with pervasive antagonistic activities predicted by machine learning models, potentially playing protective roles in the human microbiome. Class II bacteriocins, one of the most abundant and diverse LAB SMs, are particularly enriched and predominant in the vaginal microbiome. We utilized metagenomic and metatranscriptomic analyses to guide our discovery of functional class II bacteriocins. Our findings suggest that these antibacterial bacteriocins have the potential to regulate microbial communities in the vagina, thereby contributing to the maintenance of microbiome homeostasis.<br><br>CONCLUSIONS: Our study systematically investigates LAB biosynthetic potential and their profiles in the human microbiome, linking them to the antagonistic contributions to microbiome homeostasis via omics analysis. These discoveries of the diverse and prevalent antagonistic SMs are expected to stimulate the mechanism study of LAB's protective roles for the microbiome and host, highlighting the potential of LAB and their bacteriocins as therapeutic alternatives. Video Abstract.}, }
@article {pmid37100405, year = {2023}, author = {Jaffe, AL and Castelle, CJ and Banfield, JF}, title = {Habitat Transition in the Evolution of Bacteria and Archaea.}, journal = {Annual review of microbiology}, volume = {77}, number = {}, pages = {193-212}, doi = {10.1146/annurev-micro-041320-032304}, pmid = {37100405}, issn = {1545-3251}, mesh = {Animals ; Archaea/genetics ; Bacteria/genetics ; *Bacteriophages ; Genomics ; *Microbiota ; }, abstract = {Related groups of microbes are widely distributed across Earth's habitats, implying numerous dispersal and adaptation events over evolutionary time. However, relatively little is known about the characteristics and mechanisms of these habitat transitions, particularly for populations that reside in animal microbiomes. Here, we review the literature concerning habitat transitions among a variety of bacterial and archaeal lineages, considering the frequency of migration events, potential environmental barriers, and mechanisms of adaptation to new physicochemical conditions, including the modification of protein inventories and other genomic characteristics. Cells dependent on microbial hosts, particularly bacteria from the Candidate Phyla Radiation, have undergone repeated habitat transitions from environmental sources into animal microbiomes. We compare their trajectories to those of both free-living cells-including the Melainabacteria, Elusimicrobia, and methanogenic archaea-and cellular endosymbionts and bacteriophages, which have made similar transitions. We conclude by highlighting major related topics that may be worthy of future study.}, }
@article {pmid37100345, year = {2024}, author = {Shen, S and Sun, T and Ding, X and Gu, X and Wang, Y and Ma, X and Li, Z and Gao, H and Ge, S and Feng, Q}, title = {The exoprotein Gbp of Fusobacterium nucleatum promotes THP-1 cell lipid deposition by binding to CypA and activating PI3K-AKT/MAPK/NF-κB pathways.}, journal = {Journal of advanced research}, volume = {57}, number = {}, pages = {93-105}, pmid = {37100345}, issn = {2090-1224}, mesh = {Humans ; NF-kappa B ; Cyclophilin A ; Fusobacterium nucleatum ; Phosphatidylinositol 3-Kinases ; Proto-Oncogene Proteins c-akt ; THP-1 Cells ; *Atherosclerosis ; Inflammation ; *Periodontitis ; Lipids ; *Calcium-Binding Proteins ; *Monosaccharide Transport Proteins ; *Periplasmic Binding Proteins ; }, abstract = {INTRODUCTION: Growing evidence has shown the correlation between periodontitis and atherosclerosis, while our knowledge on the pathogenesis of periodontitis-promoting atherosclerosis is far from sufficient.<br><br>OBJECTIVES: Illuminate the pathogenic effects of Fusobacterium nucleatum (F. nucleatum) on intracellular lipid deposition in THP-1-derived macrophages and elucidate the underlying pathogenic mechanism of how F. nucleatum promoting atherosclerosis.<br><br>METHODS AND RESULTS: F. nucleatum was frequently detected in different kinds of atherosclerotic plaques and its abundance was positively correlated with the proportion of macrophages. In vitro assays showed F. nucleatum could adhere to and invade THP-1 cells, and survive continuously in macrophages for 24&#xa0;h. F. nucleatum stimulation alone could significantly promote cellular inflammation, lipid uptake and inhibit lipid outflow. The dynamic gene expression of THP-1 cells demonstrated that F. nucleatum could time-serially induce the over-expression of multiple inflammatory related genes and activate NF-&#x3ba;B, MAPK and PI3K-AKT signaling pathways. The exoprotein of F. nucleatum, D-galactose-binding protein (Gbp), acted as one of the main pathogenic proteins to interact with the Cyclophilin A (CypA) of THP-1 cells and induced the activation of the NF- &#x3ba;B, MAPK and PI3K-AKT signaling pathways. Furthermore, use of six candidate drugs targeting to the key proteins in NF- &#x3ba;B, MAPK and PI3K-AKT pathways could dramatically decrease F. nucleatum induced inflammation and lipid deposition in THP-1 cells.<br><br>CONCLUSIONS: This study suggests that the periodontal pathogen F. nucleatum can activate macrophage PI3K-AKT/MAPK/NF-&#x3ba;B signal pathways, promotes inflammation, enhances cholesterol uptake, reduces lipid excretion, and promotes lipid deposition, which may be one of its main strategies promoting the development of atherosclerosis.}, }
@article {pmid37099803, year = {2023}, author = {Kantele, A and Riekkinen, M and Jokiranta, TS and Pakkanen, SH and Pietilä, JP and Patjas, A and Eriksson, M and Khawaja, T and Klemets, P and Marttinen, K and Siikamäki, H and Lundgren, A and Holmgren, J and Lissmats, A and Carlin, N and Svennerholm, AM}, title = {Safety and immunogenicity of ETVAX®, an oral inactivated vaccine against enterotoxigenic Escherichia coli diarrhoea: a double-blinded, randomized, placebo-controlled trial amongst Finnish travellers to Benin, West Africa.}, journal = {Journal of travel medicine}, volume = {30}, number = {7}, pages = {}, pmid = {37099803}, issn = {1708-8305}, support = {H2020-SMEInst-2016-2017//Scandinavian Biopharma/ ; 204139-101//PATH/ ; }, mesh = {Child ; Humans ; Benin ; *Enterotoxigenic Escherichia coli ; Vaccines, Inactivated ; Finland ; Lipopolysaccharides ; Africa, Western ; Diarrhea/prevention &amp; control ; Immunoglobulin A ; }, abstract = {BACKGROUND: No licensed human vaccines are available against enterotoxigenic Escherichia coli (ETEC), a major diarrhoeal pathogen affecting children in low- and middle-income countries and foreign travellers alike. ETVAX®, a multivalent oral whole-cell vaccine containing four inactivated ETEC strains and the heat-labile enterotoxin B subunit (LTB), has proved promising in Phase 1 and Phase 1/ 2 studies.<br><br>METHODS: We conducted a Phase 2b double-blinded, randomized, placebo-controlled trial amongst Finnish travellers to Benin, West Africa. This report presents study design and safety and immunogenicity data. Volunteers aged 18-65&#xa0;years were randomized 1:1 to receive ETVAX&#xae; or placebo. They visited Benin for 12&#xa0;days, provided stool and blood samples and completed adverse event (AE) forms. IgA and IgG antibodies to LTB and O78 lipopolysaccharide (LPS) were measured by electrochemiluminescence.<br><br>RESULTS: The AEs did not differ significantly between vaccine (n&#x2009;=&#x2009;374) and placebo (n&#x2009;=&#x2009;375) recipients. Of the solicited AEs, loose stools/diarrhoea (26.7/25.9%) and stomach ache (23.0/20.0%) were reported most commonly. Of all possibly/probably vaccine-related AEs, the most frequent were gastrointestinal symptoms (54.0/48.8%) and nervous system disorders (20.3/25.1%). Serious AEs were recorded for 4.3/5.6%, all unlikely to be vaccine related. Amongst the ETVAX&#xae; recipients, LTB-specific IgA antibodies increased 22-fold. For the 370/372 vaccine/placebo recipients, the frequency of &#x2265;2-fold increases against LTB was 81/2.4%, and against O78 LPS 69/2.7%. The majority of ETVAX&#xae; recipients (93%) responded to either LTB or O78.<br><br>CONCLUSIONS: This Phase 2b trial is the largest on ETVAX&#xae; undertaken amongst travellers to date. ETVAX&#xae; showed an excellent safety profile and proved strongly immunogenic, which encourages the further development of this vaccine.}, }
@article {pmid37099800, year = {2023}, author = {Gou, W and Miao, Z and Deng, K and Zheng, JS}, title = {Nutri-microbiome epidemiology, an emerging field to disentangle the interplay between nutrition and microbiome for human health.}, journal = {Protein &amp; cell}, volume = {14}, number = {11}, pages = {787-806}, pmid = {37099800}, issn = {1674-8018}, support = {2022YFA1303900//National Key R&amp;D Program of China/ ; 82204161//National Natural Science Foundation of China/ ; //Research Program of Westlake Laboratory of Life Sciences and Biomedicine/ ; 202208012//China Postdoctoral Science Foundation/ ; }, mesh = {Humans ; Diet ; *Microbiota ; *Gastrointestinal Microbiome ; }, abstract = {Diet and nutrition have a substantial impact on the human microbiome, and interact with the microbiome, especially gut microbiome, to modulate various diseases and health status. Microbiome research has also guided the nutrition field to a more integrative direction, becoming an essential component of the rising area of precision nutrition. In this review, we provide a broad insight into the interplay among diet, nutrition, microbiome, and microbial metabolites for their roles in the human health. Among the microbiome epidemiological studies regarding the associations of diet and nutrition with microbiome and its derived metabolites, we summarize those most reliable findings and highlight evidence for the relationships between diet and disease-associated microbiome and its functional readout. Then, the latest advances of the microbiome-based precision nutrition research and multidisciplinary integration are described. Finally, we discuss several outstanding challenges and opportunities in the field of nutri-microbiome epidemiology.}, }
@article {pmid37099704, year = {2023}, author = {Choi, JM and Ji, M and Watson, LT and Zhang, L}, title = {DeepMicroGen: a generative adversarial network-based method for longitudinal microbiome data imputation.}, journal = {Bioinformatics (Oxford, England)}, volume = {39}, number = {5}, pages = {}, pmid = {37099704}, issn = {1367-4811}, mesh = {Humans ; Longitudinal Studies ; *Microbiota ; Neural Networks, Computer ; Sample Size ; Time Factors ; }, abstract = {MOTIVATION: The human microbiome, which is linked to various diseases by growing evidence, has a profound impact on human health. Since changes in the composition of the microbiome across time are associated with disease and clinical outcomes, microbiome analysis should be performed in a longitudinal study. However, due to limited sample sizes and differing numbers of timepoints for different subjects, a significant amount of data cannot be utilized, directly affecting the quality of analysis results. Deep generative models have been proposed to address this lack of data issue. Specifically, a generative adversarial network (GAN) has been successfully utilized for data augmentation to improve prediction tasks. Recent studies have also shown improved performance of GAN-based models for missing value imputation in a multivariate time series dataset compared with traditional imputation methods.<br><br>RESULTS: This work proposes DeepMicroGen, a bidirectional recurrent neural network-based GAN model, trained on the temporal relationship between the observations, to impute the missing microbiome samples in longitudinal studies. DeepMicroGen outperforms standard baseline imputation methods, showing the lowest mean absolute error for both simulated and real datasets. Finally, the proposed model improved the predicted clinical outcome for allergies, by providing imputation for an incomplete longitudinal dataset used to train the classifier.<br><br>DeepMicroGen is publicly available at https://github.com/joungmin-choi/DeepMicroGen.}, }
@article {pmid37099694, year = {2023}, author = {Li, B and Wang, T and Qian, M and Wang, S}, title = {MKMR: a multi-kernel machine regression model to predict health outcomes using human microbiome data.}, journal = {Briefings in bioinformatics}, volume = {24}, number = {3}, pages = {}, doi = {10.1093/bib/bbad158}, pmid = {37099694}, issn = {1477-4054}, mesh = {Humans ; Phylogeny ; *Microbiota ; Computer Simulation ; Neural Networks, Computer ; Outcome Assessment, Health Care ; }, abstract = {Studies have found that human microbiome is associated with and predictive of human health and diseases. Many statistical methods developed for microbiome data focus on different distance metrics that can capture various information in microbiomes. Prediction models were also developed for microbiome data, including deep learning methods with convolutional neural networks that consider both taxa abundance profiles and taxonomic relationships among microbial taxa from a phylogenetic tree. Studies have also suggested that a health outcome could associate with multiple forms of microbiome profiles. In addition to the abundance of some taxa that are associated with a health outcome, the presence/absence of some taxa is also associated with and predictive of the same health outcome. Moreover, associated taxa may be close to each other on a phylogenetic tree or spread apart on a phylogenetic tree. No prediction models currently exist that use multiple forms of microbiome-outcome associations. To address this, we propose a multi-kernel machine regression (MKMR) method that is able to capture various types of microbiome signals when doing predictions. MKMR utilizes multiple forms of microbiome signals through multiple kernels being transformed from multiple distance metrics for microbiomes and learn an optimal conic combination of these kernels, with kernel weights helping us understand contributions of individual microbiome signal types. Simulation studies suggest a much-improved prediction performance over competing methods with mixture of microbiome signals. Real data applicants to predict multiple health outcomes using throat and gut microbiome data also suggest a better prediction of MKMR than that of competing methods.}, }
@article {pmid37097879, year = {2023}, author = {Stewart, CJ}, title = {2022 Fleming Prize Lecture: diet-microbe-host interaction in early life.}, journal = {Journal of medical microbiology}, volume = {72}, number = {4}, pages = {}, doi = {10.1099/jmm.0.001662}, pmid = {37097879}, issn = {1473-5644}, mesh = {Infant ; Female ; Infant, Newborn ; Humans ; Middle Aged ; *Infant, Premature ; Host Microbial Interactions ; Milk, Human ; *Microbiota ; Diet ; }, abstract = {The last decade has witnessed a meteoric rise in research focused on characterizing the human microbiome and identifying associations with disease risk. The advent of sequencing technology has all but eradicated gel-based fingerprinting approaches for studying microbial ecology, while at the same time traditional microbiological culture is undergoing a renaissance. Although multiplexed high-throughput sequencing is relatively new, the discoveries leading to this are nearly 50 years old, coinciding with the inaugural Microbiology Society Fleming Prize lecture. It was an honour to give the 2022 Fleming Prize lecture and this review will cover the topics from that lecture. The focus will be on the bacterial community in early life, beginning with term infants before moving on to infants delivered prematurely. The review will discuss recent work showing how human milk oligosaccharides (HMOs), an abundant but non-nutritious component of breast milk, can modulate infant microbiome and promote the growth of Bifidobacterium spp. This has important connotations for preterm infants at risk of necrotizing enterocolitis, a devastating intestinal disease representing the leading cause of death and long-term morbidity in this population. With appropriate mechanistic studies, it may be possible to harness the power of breast milk bioactive factors and infant gut microbiome to improve short- and long-term health in infants.}, }
@article {pmid37086551, year = {2023}, author = {Dmitrieva, K and Maslennikov, R and Vasilieva, E and Aliev, S and Bakhitov, V and Marcinkevich, V and Levshina, A and Kozlov, E and Ivashkin, V and Poluektova, E}, title = {Impact of vaccination against the novel coronavirus infection (COVID-19) with Sputnik V on mortality during the delta variant surge.}, journal = {Journal of infection and public health}, volume = {16}, number = {6}, pages = {922-927}, pmid = {37086551}, issn = {1876-035X}, mesh = {Humans ; *COVID-19 Vaccines ; Retrospective Studies ; SARS-CoV-2 ; *COVID-19/prevention &amp; control ; Vaccination ; }, abstract = {OBJECTIVES: The aim is to study impact of vaccination against the novel coronavirus disease (COVID-19) with Sputnik V on mortality during the period of predominance of the delta variant of SARS-CoV-2.<br><br>METHODS: This was a retrospective cohort study of individuals with state health insurance at the Moscow Ambulatory Center. The cohorts included 41,444 persons vaccinated with Sputnik V, 15,566 survivors of COVID-19, and 71,377 non-immune persons. The deaths of patients that occurred from June 1, 2021, to August 31, 2021, were analyzed.<br><br>RESULTS: Overall (0.39&#xa0;% vs. 1.92&#xa0;%; p&#xa0;<&#xa0;0.001), COVID-19-related (0.06&#xa0;% vs. 0.83&#xa0;%; p&#xa0;<&#xa0;0.001), and non-COVID mortality (0.33&#xa0;% vs. 1.09&#xa0;%; p&#xa0;<&#xa0;0.001) was lower among vaccinated individuals than among non-immune individuals. The efficacy of vaccination against death from COVID-19 was 96&#xa0;% [95&#xa0;% CI 91-98&#xa0;%] in the general population, 100&#xa0;% among those aged 18-50 years, 97&#xa0;% [95&#xa0;% CI 76-100&#xa0;%] among those aged 51-70 years, 98&#xa0;% [95&#xa0;% CI 90-100&#xa0;%] among those aged 71-85 years, and 88&#xa0;% [95&#xa0;% CI 49-97&#xa0;%] among those aged >&#xa0;85 years.<br><br>CONCLUSION: COVID-19 vaccination with Sputnik V is associated with a decrease in overall and COVID-19-related mortality and is not with increased non-COVID mortality.}, }
@article {pmid37085428, year = {2023}, author = {Jin, C and Qin, L and Liu, Z and Li, X and Gao, X and Cao, Y and Zhao, S and Wang, J and Han, T and Yan, L and Song, J and Zhang, F and Liu, F and Zhang, Y and Huang, Y and Song, Y and Liu, Y and Yao, Z and Chen, H and Zhang, Z and Zhao, S and Feng, Y and Zhang, YN and Qian, Y and Sun, T and Feng, Q and Zhao, H}, title = {Comparative analysis of the vaginal microbiome of healthy and polycystic ovary syndrome women: a large cross-sectional study.}, journal = {Reproductive biomedicine online}, volume = {46}, number = {6}, pages = {1005-1016}, doi = {10.1016/j.rbmo.2023.02.002}, pmid = {37085428}, issn = {1472-6491}, mesh = {Female ; Humans ; *Polycystic Ovary Syndrome ; Cross-Sectional Studies ; RNA, Ribosomal, 16S/genetics ; Anti-Mullerian Hormone ; *Microbiota ; }, abstract = {RESEARCH QUESTION: What are the different features of the vaginal microbiome (VMB) between patients with polycystic ovary syndrome (PCOS) and healthy women?<br><br>DESIGN: A cross-sectional study was conducted at a single academic university-affiliated centre. A total of 1446 participants were recruited (PCOS group, n =713, control group, n&#x202f;=&#x202f;733). Vaginal swabs were analysed using 16S rRNA gene sequencing. The diversity and composition of the microbiome were compared between the PCOS group and the control group. Microbial interaction networks and functional prediction were investigated.<br><br>RESULTS: The PCOS group had a higher alpha diversity than the control group (Shannon P&#x202f;=&#x202f;0.03, Simpson P&#x202f;=&#x202f;0.02), and higher intra-group variability was observed in PCOS group (P < 2.2E-16). At the genus level, the proportion of Lactobacillus decreased (85.1% versus 89.3%, false discovery rate [FDR]&#x202f;=&#x202f;0.02), whereas the proportion of Gardnerella vaginalis and Ureaplasma increased in the PCOS group (5.1% versus 3.3%, FDR&#x202f;=&#x202f;0.006; 1.2% versus 0.6%, FDR&#x202f;=&#x202f;0.002, respectively). Lactobacillus acidophilus, Prevotella buccalis and G. vaginalis were identified as the main differential species. L. acidophilus was positively correlated with serum levels of anti-M&#xfc;llerian hormone (AMH), and triglyceride (P&#x202f;=&#x202f;2.01E-05, P&#x202f;=&#x202f;0.004, respectively). P. buccalis was negatively correlated with serum levels of AMH and testosterone (P&#x202f;=&#x202f;0.002, P&#x202f;=&#x202f;0.003, respectively). G. vaginalis was positively correlated with serum levels of AMH, oestradiol and progesterone (P&#x202f;=&#x202f;0.004, P&#x202f;=&#x202f;0.005, P&#x202f;=&#x202f;0.03, respectively). The VMB interaction network indicated that Lactobacillus crispus, Prevotella timonensis, and P. buccalis could be key drivers in the PCOS group. Overall, 55 predicted genes were found to be differentially abundant between PCOS and the control (FDRs < 0.25).<br><br>CONCLUSIONS: The PCOS group had a higher diversity of vaginal microbiome and showed an enhanced level of heterogeneity. The proportion of Lactobacillus in the PCOS group decreased, whereas the proportions of Gardnerella and Ureaplasma increased. These results warrant further research that can validate the correlation between PCOS and VMB.}, }
@article {pmid37081054, year = {2023}, author = {Hoisington, AJ and Stamper, CE and Bates, KL and Stanislawski, MA and Flux, MC and Postolache, TT and Lowry, CA and Brenner, LA}, title = {Human microbiome transfer in the built environment differs based on occupants, objects, and buildings.}, journal = {Scientific reports}, volume = {13}, number = {1}, pages = {6446}, pmid = {37081054}, issn = {2045-2322}, support = {K01 HL157658/HL/NHLBI NIH HHS/United States ; }, mesh = {Humans ; *Microbiota ; Built Environment ; Skin/microbiology ; }, abstract = {Compared to microbiomes on other skin sites, the bacterial microbiome of the human hand has been found to have greater variability across time. To increase understanding regarding the longitudinal transfer of the hand microbiome to objects in the built environment, and vice versa, 22 participants provided skin microbiome samples from their dominant hands, as well as from frequently and infrequently touched objects in their office environments. Additional longitudinal samples from home environments were obtained from a subset of 11 participants. We observed stability of the microbiomes of both the hand and built environments within the office and home settings; however, differences in the microbial communities were detected across the two built environments. Occupants' frequency of touching an object correlated to that object having a higher relative abundance of human microbes, yet the percent of shared microbes was variable by participants. Finally, objects that were horizontal surfaces in the built environment had higher microbial diversity as compared to objects and the occupants' hands. This study adds to the existing knowledge of microbiomes of the built environment, enables more detailed studies of indoor microbial transfer, and contributes to future models and building interventions to reduce negative outcomes and improve health and well-being.}, }
@article {pmid37080202, year = {2023}, author = {Bedree, JK and Kerns, K and Chen, T and Lima, BP and Liu, G and Ha, P and Shi, J and Pan, HC and Kim, JK and Tran, L and Minot, SS and Hendrickson, EL and Lamont, EI and Schulte, F and Hardt, M and Stephens, D and Patel, M and Kokaras, A and Stodieck, L and Shirazi-Fard, Y and Wu, B and Kwak, JH and Ting, K and Soo, C and McLean, JS and He, X and Shi, W}, title = {Specific host metabolite and gut microbiome alterations are associated with bone loss during spaceflight.}, journal = {Cell reports}, volume = {42}, number = {5}, pages = {112299}, pmid = {37080202}, issn = {2211-1247}, support = {KL2 TR002317/TR/NCATS NIH HHS/United States ; F31 DE026057/DE/NIDCR NIH HHS/United States ; R01 DE023810/DE/NIDCR NIH HHS/United States ; R01 DE029353/DE/NIDCR NIH HHS/United States ; R01 AR061399/AR/NIAMS NIH HHS/United States ; R01 AR068835/AR/NIAMS NIH HHS/United States ; }, mesh = {Humans ; *Gastrointestinal Microbiome ; RNA, Ribosomal, 16S/genetics ; Chromatography, Liquid ; Travel ; Tandem Mass Spectrometry ; *Space Flight ; }, abstract = {Understanding the axis of the human microbiome and physiological homeostasis is an essential task in managing deep-space-travel-associated health risks. The NASA-led Rodent Research 5 mission enabled an ancillary investigation of the gut microbiome, varying exposure to microgravity (flight) relative to ground controls in the context of previously shown bone mineral density (BMD) loss that was observed in these flight groups. We demonstrate elevated abundance of Lactobacillus murinus and Dorea sp. during microgravity exposure relative to ground control through whole-genome sequencing and 16S rRNA analyses. Specific functionally assigned gene clusters of L. murinus and Dorea sp. capable of producing metabolites, lactic acid, leucine/isoleucine, and glutathione are enriched. These metabolites are elevated in the microgravity-exposed host serum as shown by liquid chromatography-tandem mass spectrometry (LC-MS/MS) metabolomic analysis. Along with BMD loss, ELISA reveals increases in osteocalcin and reductions in tartrate-resistant acid phosphatase 5b signifying additional loss of bone homeostasis in flight.}, }
@article {pmid37077531, year = {2023}, author = {Liu, P and Lu, Y and Li, R and Chen, X}, title = {Use of probiotic lactobacilli in the treatment of vaginal infections: In vitro and in vivo investigations.}, journal = {Frontiers in cellular and infection microbiology}, volume = {13}, number = {}, pages = {1153894}, pmid = {37077531}, issn = {2235-2988}, mesh = {Infant, Newborn ; Female ; Humans ; Lactobacillus ; *Premature Birth ; Vagina ; *Vulvovaginitis ; *Probiotics/therapeutic use ; }, abstract = {The vaginal microbiome is a distinct component of the human microbiome that is colonized by a wide variety of microorganisms. Lactobacilli are the most frequently identified microorganisms in the healthy human vagina. These Gram-positive bacilli can acidify the vaginal microenvironment, inhibit the proliferation of other pathogenic microorganisms, and promote the maintenance of a eubiotic vaginal microbiome. However, a vaginal flora with a reduced proportion or abundance of lactobacilli is associated with various vaginal infections that have been linked to serious health consequences such as infertility, preterm birth, pelvic inflammatory disease, premature rupture of membranes, and miscarriage. Due to their "Generally Recognized as Safe" classification and critical role in vaginal health, probiotic lactobacilli have been widely used as an alternative or adjunct to traditional antibiotic therapy for the treatment of vaginal infections and restoration of the vaginal microbiome. This review focuses on the significant role of probiotic lactobacilli in the vaginal microenvironment and discusses the use of probiotic lactobacilli in the treatment of female vaginal infections in vitro and in vivo.}, }
@article {pmid37074210, year = {2023}, author = {Zhang, YG and Xia, Y and Zhang, J and Deb, S and Garrett, S and Sun, J}, title = {Intestinal vitamin D receptor protects against extraintestinal breast cancer tumorigenesis.}, journal = {Gut microbes}, volume = {15}, number = {1}, pages = {2202593}, pmid = {37074210}, issn = {1949-0984}, support = {R01 DK105118/DK/NIDDK NIH HHS/United States ; R01 DK114126/DK/NIDDK NIH HHS/United States ; }, mesh = {Humans ; Mice ; Animals ; Female ; Receptors, Calcitriol/genetics ; *Breast Neoplasms/prevention &amp; control/metabolism ; Dysbiosis/metabolism ; *Gastrointestinal Microbiome ; Inflammation/metabolism ; Carcinogenesis/metabolism ; Cell Transformation, Neoplastic ; *Gastrointestinal Diseases/metabolism ; Bacteria/metabolism ; Intestinal Mucosa/microbiology ; }, abstract = {The microbiota plays critical roles in regulating the function and health of the intestine and extraintestinal organs. A fundamental question is whether an intestinal-microbiome-breast axis exists during the development of breast cancer. If so, what are the roles of host factors? Vitamin D receptor (VDR) involves host factors and the human microbiome. Vdr gene variation shapes the human microbiome, and VDR deficiency leads to dysbiosis. We hypothesized that intestinal VDR protects hosts against tumorigenesis in the breast. We examined a 7,12-dimethylbenzanthracene (DMBA)-induced breast cancer model in intestinal epithelial VDR knockout (VDR[ΔIEC]) mice with dysbiosis. We reported that VDR[ΔIEC] mice with dysbiosis are more susceptible to breast cancer induced by DMBA. Intestinal and breast microbiota analysis showed that VDR deficiency leads to a bacterial profile shift from normal to susceptible to carcinogenesis. We found enhanced bacterial staining within breast tumors. At the molecular and cellular levels, we identified the mechanisms by which intestinal epithelial VDR deficiency led to increased gut permeability, disrupted tight junctions, microbial translocation, and enhanced inflammation, thus increasing tumor size and number in the breast. Furthermore, treatment with the beneficial bacterial metabolite butyrate or the probiotic Lactobacillus plantarum reduced breast tumors, enhanced tight junctions, inhibited inflammation, increased butyryl-CoA transferase, and decreased levels of breast Streptococcus bacteria in VDR[ΔIEC] mice. The gut microbiome contributes to the pathogenesis of diseases not only in the intestine but also in the breast. Our study provides insights into the mechanism by which intestinal VDR dysfunction and gut dysbiosis lead to a high risk of extraintestinal tumorigenesis. Gut-tumor-microbiome interactions represent a new target in the prevention and treatment of breast cancer.}, }
@article {pmid37070603, year = {2023}, author = {Segota, I and Watrous, JD and Kantz, ED and Nallamshetty, S and Tiwari, S and Cheng, S and Jain, M and Long, T}, title = {Reconstructing the landscape of gut microbial species across 29,000 diverse individuals.}, journal = {Nucleic acids research}, volume = {51}, number = {9}, pages = {4178-4190}, pmid = {37070603}, issn = {1362-4962}, support = {R01 HL143227/HL/NHLBI NIH HHS/United States ; R01ES027595/NH/NIH HHS/United States ; COVID-19-8900-12/CX/CSRD VA/United States ; }, mesh = {Humans ; Bacteria/classification ; *Gastrointestinal Microbiome/genetics ; *Microbiota ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; }, abstract = {The human gut microbiome has been linked to health and disease. Investigation of the human microbiome has largely employed 16S amplicon sequencing, with limited ability to distinguish microbes at the species level. Herein, we describe the development of Reference-based Exact Mapping (RExMap) of microbial amplicon variants that enables mapping of microbial species from standard 16S sequencing data. RExMap analysis of 16S data captures ∼75% of microbial species identified by whole-genome shotgun sequencing, despite hundreds-fold less sequencing depth. RExMap re-analysis of existing 16S data from 29,349 individuals across 16 regions from around the world reveals a detailed landscape of gut microbial species across populations and geography. Moreover, RExMap identifies a core set of fifteen gut microbes shared by humans. Core microbes are established soon after birth and closely associate with BMI across multiple independent studies. RExMap and the human microbiome dataset are presented as resources with which to explore the role of the human microbiome.}, }
@article {pmid37065164, year = {2023}, author = {Wan, X and Takala, TM and Huynh, VA and Ahonen, SL and Paulin, L and Björkroth, J and Sironen, T and Kant, R and Saris, P}, title = {Comparative genomics of 40 Weissella paramesenteroides strains.}, journal = {Frontiers in microbiology}, volume = {14}, number = {}, pages = {1128028}, pmid = {37065164}, issn = {1664-302X}, abstract = {Weissella strains are often detected in spontaneously fermented foods. Because of their abilities to produce lactic acid and functional exopolysaccharides as well as their probiotic traits, Weissella spp. improve not only the sensorial properties but also nutritional values of the fermented food products. However, some Weissella species have been associated with human and animal diseases. In the era of vast genomic sequencing, new genomic/genome data are becoming available to the public on daily pace. Detailed genomic analyses are due to provide a full understanding of individual Weissella species. In this study, the genomes of six Weissella paramesenteroides strains were de novo sequenced. The genomes of 42 W. paramesenteroides strains were compared to discover their metabolic and functional potentials in food fermentation. Comparative genomics and metabolic pathway reconstructions revealed that W. paramesenteroides is a compact group of heterofermentative bacteria with good capacity of producing secondary metabolites and vitamin Bs. Since the strains rarely harbored plasmid DNA, they did not commonly possess the genes associated with bacteriocin production. All 42 strains were shown to bear vanT gene from the glycopeptide resistance gene cluster vanG. Yet none of the strains carried virulence genes.}, }
@article {pmid37065142, year = {2023}, author = {Wang, X and Chen, D and Du, J and Cheng, K and Fang, C and Liao, X and Liu, Y and Sun, J and Lian, X and Ren, H}, title = {Occupational exposure in swine farm defines human skin and nasal microbiota.}, journal = {Frontiers in microbiology}, volume = {14}, number = {}, pages = {1117866}, pmid = {37065142}, issn = {1664-302X}, abstract = {Anthropogenic environments take an active part in shaping the human microbiome. Herein, we studied skin and nasal microbiota dynamics in response to the exposure in confined and controlled swine farms to decipher the impact of occupational exposure on microbiome formation. The microbiota of volunteers was longitudinally profiled in a 9-months survey, in which the volunteers underwent occupational exposure during 3-month internships in swine farms. By high-throughput sequencing, we showed that occupational exposure compositionally and functionally reshaped the volunteers' skin and nasal microbiota. The exposure in farm A reduced the microbial diversity of skin and nasal microbiota, whereas the microbiota of skin and nose increased after exposure in farm B. The exposure in different farms resulted in compositionally different microbial patterns, as the abundance of Actinobacteria sharply increased at expense of Firmicutes after exposure in farm A, yet Proteobacteria became the most predominant in the volunteers in farm B. The remodeled microbiota composition due to exposure in farm A appeared to stall and persist, whereas the microbiota of volunteers in farm B showed better resilience to revert to the pre-exposure state within 9 months after the exposure. Several metabolic pathways, for example, the styrene, aminobenzoate, and N-glycan biosynthesis, were significantly altered through our PICRUSt analysis, and notably, the function of beta-lactam resistance was predicted to enrich after exposure in farm A yet decrease in farm B. We proposed that the differently modified microbiota patterns might be coordinated by microbial and non-microbial factors in different swine farms, which were always environment-specific. This study highlights the active role of occupational exposure in defining the skin and nasal microbiota and sheds light on the dynamics of microbial patterns in response to environmental conversion.}, }
@article {pmid37054680, year = {2023}, author = {Shen, J and Zhang, J and Mo, L and Li, Y and Li, Y and Li, C and Kuang, X and Tao, Z and Qu, Z and Wu, L and Chen, J and Liu, S and Zeng, L and He, Z and Chen, Z and Deng, Y and Zhang, T and Li, B and Dai, L and Ma, Y}, title = {Large-scale phage cultivation for commensal human gut bacteria.}, journal = {Cell host &amp; microbe}, volume = {31}, number = {4}, pages = {665-677.e7}, doi = {10.1016/j.chom.2023.03.013}, pmid = {37054680}, issn = {1934-6069}, mesh = {Humans ; *Bacteriophages ; *Gastrointestinal Microbiome/genetics ; Bacteria/genetics ; *Microbiota ; Symbiosis ; }, abstract = {Phages are highly abundant in the human gut, yet most of them remain uncultured. Here, we present a gut phage isolate collection (GPIC) containing 209 phages for 42 commensal human gut bacterial species. Genome analysis of the phages identified 34 undescribed genera. We discovered 22 phages from the Salasmaviridae family that have small genomes (∼10-20 kbp) and infect Gram-positive bacteria. Two phages from a candidate family, Paboviridae, with high prevalence in the human gut were also identified. Infection assays showed that Bacteroides and Parabacteroides phages are specific to a bacterial species, and strains of the same species also exhibit substantial variations in phage susceptibility. A cocktail of 8 phages with a broad host range for Bacteroides fragilis strains effectively reduced their abundance in complex host-derived communities in vitro. Our study expands the diversity of cultured human gut bacterial phages and provides a valuable resource for human microbiome engineering.}, }
@article {pmid37047594, year = {2023}, author = {Laterza, L and Putignani, L and Settanni, CR and Petito, V and Varca, S and De Maio, F and Macari, G and Guarrasi, V and Gremese, E and Tolusso, B and Wlderk, G and Pirro, MA and Fanali, C and Scaldaferri, F and Turchini, L and Amatucci, V and Sanguinetti, M and Gasbarrini, A}, title = {Ecology and Machine Learning-Based Classification Models of Gut Microbiota and Inflammatory Markers May Evaluate the Effects of Probiotic Supplementation in Patients Recently Recovered from COVID-19.}, journal = {International journal of molecular sciences}, volume = {24}, number = {7}, pages = {}, pmid = {37047594}, issn = {1422-0067}, support = {na//Actial Farmaceutica/ ; na//Fondazione Roma/ ; }, mesh = {Humans ; *Gastrointestinal Microbiome/genetics ; Citrulline ; *COVID-19 ; *Probiotics/therapeutic use/pharmacology ; Cytokines ; Bifidobacterium ; Machine Learning ; }, abstract = {Gut microbiota (GM) modulation can be investigated as possible solution to enhance recovery after COVID-19. An open-label, single-center, single-arm, pilot, interventional study was performed by enrolling twenty patients recently recovered from COVID-19 to investigate the role of a mixed probiotic, containing Lactobacilli, Bifidobacteria and Streptococcus thermophilus, on gastrointestinal symptoms, local and systemic inflammation, intestinal barrier integrity and GM profile. Gastrointestinal Symptom Rating Scale, cytokines, inflammatory, gut permeability, and integrity markers were evaluated before (T0) and after 8 weeks (T1) of probiotic supplementation. GM profiling was based on 16S-rRNA targeted-metagenomics and QIIME 2.0, LEfSe and PICRUSt computational algorithms. Multiple machine learning (ML) models were trained to classify GM at T0 and T1. A statistically significant reduction of IL-6 (p < 0.001), TNF-α (p < 0.001) and IL-12RA (p < 0.02), citrulline (p value < 0.001) was reported at T1. GM global distribution and microbial biomarkers strictly reflected probiotic composition, with a general increase in Bifidobacteria at T1. Twelve unique KEGG orthologs were associated only to T0, including tetracycline resistance cassettes. ML classified the GM at T1 with 100% score at phylum level. Bifidobacteriaceae and Bifidobacterium spp. inversely correlated to reduction of citrulline and inflammatory cytokines. Probiotic supplementation during post-COVID-19 may trigger anti-inflammatory effects though Bifidobacteria and related-metabolism enhancement.}, }
@article {pmid37046097, year = {2023}, author = {Metwaly, A and Haller, D}, title = {Elucidating the transmission landscape of the human microbiome.}, journal = {Nature reviews. Gastroenterology &amp; hepatology}, volume = {20}, number = {7}, pages = {415-416}, pmid = {37046097}, issn = {1759-5053}, mesh = {Humans ; *Microbiota ; *Gastrointestinal Microbiome ; }, }
@article {pmid37042769, year = {2023}, author = {Ma, X and Sun, T and Zhou, J and Zhi, M and Shen, S and Wang, Y and Gu, X and Li, Z and Gao, H and Wang, P and Feng, Q}, title = {Pangenomic Study of Fusobacterium nucleatum Reveals the Distribution of Pathogenic Genes and Functional Clusters at the Subspecies and Strain Levels.}, journal = {Microbiology spectrum}, volume = {11}, number = {3}, pages = {e0518422}, pmid = {37042769}, issn = {2165-0497}, mesh = {*Fusobacterium nucleatum/genetics ; Phylogeny ; *Genomics ; Base Sequence ; Virulence Factors/genetics ; }, abstract = {Fusobacterium nucleatum is a prevalent periodontal pathogen and is associated with many systemic diseases. Our knowledge of the genomic characteristics and pathogenic effectors of different F. nucleatum strains is limited. In this study, we completed the whole genome assembly of the 4 F. nucleatum strains and carried out a comprehensive pangenomic study of 30 strains with their complete genome sequences. Phylogenetic analysis revealed that the F. nucleatum strains are mainly divided into 4 subspecies, while 1 of the sequenced strains was classified into a new subspecies. Gene composition analysis revealed that a total of 517 "core/soft-core genes" with housekeeping functions widely distributed in almost all the strains. Each subspecies had a unique gene cluster shared by strains within the subspecies. Analysis of the virulence factors revealed that many virulence factors were widely distributed across all the strains, with some present in multiple copies. Some virulence genes showed no consistent occurrence rule at the subspecies level and were specifically distributed in certain strains. The genomic islands mainly revealed strain-specific characteristics instead of subspecies level consistency, while CRISPR types and secondary metabolite biosynthetic gene clusters were identically distributed in F. nucleatum strains from the same subspecies. The variation in amino acid sites in the adhesion protein FadA did not affect the monomer and dimer 3D structures, but it may affect the binding surface and the stability of binding to host receptors. This study provides a basis for the pathogenic study of F. nucleatum at the subspecies and strain levels. IMPORTANCE We used F. nucleatum as an example to analyze the genomic characteristics of oral pathogens at the species, subspecies, and strain levels and elucidate the similarities and differences in functional genes and virulence factors among different subspecies/strains of the same oral pathogen. We believe that the unique biological characteristics of each subspecies/strain can be attributed to the differences in functional gene clusters or the presence/absence of certain virulence genes. This study showed that F. nucleatum strains from the same subspecies had similar functional gene compositions, CRISPR types, and secondary metabolite biosynthetic gene clusters, while pathogenic genes, such as virulence genes, antibiotic resistance genes, and GIs, had more strain level specificity. The findings of this study suggest that, for microbial pathogenicity studies, we should carefully consider the subspecies/strains being used, as different strains may vary greatly.}, }
@article {pmid37040017, year = {2023}, author = {Vitetta, L}, title = {Letter on "Role of gut microbiome in immune regulation and immune checkpoint therapy of colorectal cancer".}, journal = {Medical oncology (Northwood, London, England)}, volume = {40}, number = {5}, pages = {143}, pmid = {37040017}, issn = {1559-131X}, mesh = {Humans ; *Gastrointestinal Microbiome ; Immunotherapy ; *Colorectal Neoplasms ; Tumor Microenvironment ; }, abstract = {Investigations that decipher the human microbiome have reformed the way medicine is focusing on bacteria. An interesting research review recently published in the journal of Digestive Diseases and Sciences conceivably linked adjunctive commensal intestinal bacteria with the capacity to modulate the immune microenvironment towards immune checkpoint inhibitor (ICIs) efficacy of cancer immunotherapy. Evidence has emerged that the intestinal microbiome can modulate outcomes to ICIs therapies via two major mechanisms, namely mechanisms that are antigen-specific (i.e., epitopes are shared between microbial and tumour antigens that can enhance or reduce anti-tumour immune responses) and those mechanisms that are antigen-independent (i.e., modulation of responses to ICIs by engaging innate and/or adaptive immune cells).}, }
@article {pmid37039671, year = {2023}, author = {Gu, W and Koh, H and Jang, H and Lee, B and Kang, B}, title = {MiSurv: an Integrative Web Cloud Platform for User-Friendly Microbiome Data Analysis with Survival Responses.}, journal = {Microbiology spectrum}, volume = {11}, number = {3}, pages = {e0505922}, pmid = {37039671}, issn = {2165-0497}, mesh = {Humans ; Cloud Computing ; *Diabetes Mellitus, Type 1 ; *Gastrointestinal Microbiome ; *Microbiota ; }, abstract = {Investigators have studied the treatment effects on human health or disease, the treatment effects on human microbiome, and the roles of the microbiome on human health or disease. Especially, in a clinical trial, investigators commonly trace disease status over a lengthy period to survey the sequential disease progression for different treatment groups (e.g., treatment versus placebo, new treatment versus old treatment). Hence, disease responses are often available in the form of survival (i.e., time-to-event) responses stratified by treatment groups. While the recent web cloud platforms have enabled user-friendly microbiome data processing and analytics, there is currently no web cloud platform to analyze microbiome data with survival responses. Therefore, we introduce here an integrative web cloud platform, called MiSurv, for comprehensive microbiome data analysis with survival responses. IMPORTANCE MiSurv consists of a data processing module and its following four data analytic modules: (i) Module 1: Comparative survival analysis between treatment groups, (ii) Module 2: Comparative analysis in microbial composition between treatment groups, (iii) Module 3: Association testing between microbial composition and survival responses, (iv) Module 4: Prediction modeling using microbial taxa on survival responses. We demonstrate its use through an example trial on the effects of antibiotic use on the survival rate against type 1 diabetes (T1D) onset and gut microbiome composition, respectively, and the effects of the gut microbiome on the survival rate against T1D onset. MiSurv is freely available on our web server (http://misurv.micloud.kr) or can alternatively run on the user's local computer (https://github.com/wg99526/MiSurvGit).}, }
@article {pmid37034781, year = {2023}, author = {Boodaghidizaji, M and Jungles, T and Chen, T and Zhang, B and Landay, A and Keshavarzian, A and Hamaker, B and Ardekani, A}, title = {Machine learning based gut microbiota pattern and response to fiber as a diagnostic tool for chronic inflammatory diseases.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2023.03.27.534466}, pmid = {37034781}, issn = {2692-8205}, abstract = {Gut microbiota has been implicated in the pathogenesis of multiple gastrointestinal (GI) and systemic metabolic and inflammatory disorders where disrupted gut microbiota composition and function (dysbiosis) has been found in multiple studies. Thus, human microbiome data has a potential to be a great source of information for the diagnosis and disease characteristics (phenotypes, disease course, therapeutic response) of diseases with dysbiotic microbiota community. However, multiple attempts to leverage gut microbiota taxonomic data for diagnostic and disease characterization have failed due to significant inter-individual variability of microbiota community and overlap of disrupted microbiota communities among multiple diseases. One potential approach is to look at the microbiota community pattern and response to microbiota modifiers like dietary fiber in different disease states. This approach is now feasible by availability of machine learning that is able to identify hidden patterns in the human microbiome and predict diseases. Accordingly, the aim of our study was to test the hypothesis that application of machine learning algorithms can distinguish stool microbiota pattern and microbiota response to fiber between diseases where overlapping dysbiotic microbiota have been previously reported. Here, we have applied machine learning algorithms to distinguish between Parkinson's disease, Crohn's disease (CD), ulcerative colitis (UC), human immune deficiency virus (HIV), and healthy control (HC) subjects in the presence and absence of fiber treatments. We have shown that machine learning algorithms can classify diseases with accuracy as high as 95%. Furthermore, machine learning methods applied to the microbiome data to predict UC vs CD led to prediction accuracy as high as 90%.}, }
@article {pmid37032359, year = {2023}, author = {Spatz, M and Da Costa, G and Ventin-Holmberg, R and Planchais, J and Michaudel, C and Wang, Y and Danne, C and Lapiere, A and Michel, ML and Kolho, KL and Langella, P and Sokol, H and Richard, ML}, title = {Antibiotic treatment using amoxicillin-clavulanic acid impairs gut mycobiota development through modification of the bacterial ecosystem.}, journal = {Microbiome}, volume = {11}, number = {1}, pages = {73}, pmid = {37032359}, issn = {2049-2618}, mesh = {Humans ; Mice ; Animals ; *Amoxicillin-Potassium Clavulanate Combination/pharmacology ; Anti-Bacterial Agents/pharmacology ; Gastrointestinal Tract/microbiology ; *Microbiota ; Fungi ; Bacteria/genetics ; }, abstract = {BACKGROUND: Effects of antibiotics on gut bacteria have been widely studied, but very little is known about the consequences of such treatments on the fungal microbiota (mycobiota). It is commonly believed that fungal load increases in the gastrointestinal tract following antibiotic treatment, but better characterization is clearly needed of how antibiotics directly or indirectly affect the mycobiota and thus the entire microbiota.<br><br>DESIGN: We used samples from humans (infant cohort) and mice (conventional and human microbiota-associated mice) to study the consequences of antibiotic treatment (amoxicillin-clavulanic acid) on the intestinal microbiota. Bacterial and fungal communities were subjected to qPCR or 16S and ITS2 amplicon-based sequencing for microbiota analysis. In vitro assays further characterized bacterial-fungal interactions, with mixed cultures between specific bacteria and fungi.<br><br>RESULTS: Amoxicillin-clavulanic acid treatment triggered a decrease in the total fungal population in mouse feces, while other antibiotics had opposite effects on the fungal load. This decrease is accompanied by a total remodelling of the fungal population with the enrichment in Aspergillus, Cladosporium, and Valsa genera. In the presence of amoxicillin-clavulanic acid, microbiota analysis showed a remodeling of bacterial microbiota with an increase in specific bacteria belonging to the Enterobacteriaceae. Using in vitro assays, we isolated different Enterobacteriaceae species and explored their effect on different fungal strains. We showed that Enterobacter hormaechei was able to reduce the fungal population in vitro and in vivo through yet unknown mechanisms.<br><br>CONCLUSIONS: Bacteria and fungi have strong interactions within the microbiota; hence, the perturbation initiated by an antibiotic treatment targeting the bacterial community can have complex consequences and can induce opposite alterations of the mycobiota. Interestingly, amoxicillin-clavulanic acid treatment has a deleterious effect on the fungal community, which may have been partially due to the overgrowth of specific bacterial strains with inhibiting or competing effects on fungi. This study provides new insights into the interactions between fungi and bacteria of the intestinal microbiota and might offer new strategies to modulate gut microbiota equilibrium. Video Abstract.}, }
@article {pmid37032329, year = {2023}, author = {Bazant, W and Blevins, AS and Crouch, K and Beiting, DP}, title = {Improved eukaryotic detection compatible with large-scale automated analysis of metagenomes.}, journal = {Microbiome}, volume = {11}, number = {1}, pages = {72}, pmid = {37032329}, issn = {2049-2618}, mesh = {Humans ; *Metagenome/genetics ; Eukaryota/genetics ; *Microbiota/genetics ; Bacteria/genetics ; Archaea/genetics ; Metagenomics/methods ; }, abstract = {BACKGROUND: Eukaryotes such as fungi and protists frequently accompany bacteria and archaea in microbial communities. Unfortunately, their presence is difficult to study with "shotgun" metagenomic sequencing since prokaryotic signals dominate in most environments. Recent methods for eukaryotic detection use eukaryote-specific marker genes, but they do not incorporate strategies to handle the presence of eukaryotes that are not represented in the reference marker gene set, and they are not compatible with web-based tools for downstream analysis.<br><br>RESULTS: Here, we present CORRAL (for Clustering Of Related Reference ALignments), a tool for the identification of eukaryotes in shotgun metagenomic data based on alignments to eukaryote-specific marker genes and Markov clustering. Using a combination of simulated datasets, mock community standards, and large publicly available human microbiome studies, we demonstrate that our method is not only sensitive and accurate but is also capable of inferring the presence of eukaryotes not included in the marker gene reference, such as novel strains. Finally, we deploy CORRAL on our MicrobiomeDB.org resource, producing an atlas of eukaryotes present in various environments of the human body and linking their presence to study covariates.<br><br>CONCLUSIONS: CORRAL allows eukaryotic detection to be automated and carried out at scale. Implementation of CORRAL in MicrobiomeDB.org creates a running atlas of microbial eukaryotes in metagenomic studies. Since our approach is independent of the reference used, it may be applicable to other contexts where shotgun metagenomic reads are matched against redundant but non-exhaustive databases, such as the identification of bacterial virulence genes or taxonomic classification of viral reads. Video Abstract.}, }
@article {pmid37022232, year = {2023}, author = {Zimmerman, S and Tierney, BT and Patel, CJ and Kostic, AD}, title = {Quantifying Shared and Unique Gene Content across 17 Microbial Ecosystems.}, journal = {mSystems}, volume = {8}, number = {2}, pages = {e0011823}, pmid = {37022232}, issn = {2379-5077}, support = {P30 DK036836/DK/NIDDK NIH HHS/United States ; R01 AI127250/AI/NIAID NIH HHS/United States ; R01 ES032470/ES/NIEHS NIH HHS/United States ; T32 DK110919/DK/NIDDK NIH HHS/United States ; }, mesh = {Humans ; *Microbiota/genetics ; Metagenome/genetics ; *Gastrointestinal Microbiome/genetics ; Metagenomics/methods ; Genome, Bacterial ; }, abstract = {Measuring microbial diversity is traditionally based on microbe taxonomy. Here, in contrast, we aimed to quantify heterogeneity in microbial gene content across 14,183 metagenomic samples spanning 17 ecologies, including 6 human associated, 7 nonhuman host associated, and 4 in other nonhuman host environments. In total, we identified 117,629,181 nonredundant genes. The vast majority of genes (66%) occurred in only one sample (i.e., "singletons"). In contrast, we found 1,864 sequences present in every metagenome, but not necessarily every bacterial genome. Additionally, we report data sets of other ecology-associated genes (e.g., abundant in only gut ecosystems) and simultaneously demonstrated that prior microbiome gene catalogs are both incomplete and inaccurately cluster microbial genetic life (e.g., at gene sequence identities that are too restrictive). We provide our results and the sets of environmentally differentiating genes described above at http://www.microbial-genes.bio. IMPORTANCE The amount of shared genetic elements has not been quantified between the human microbiome and other host- and non-host-associated microbiomes. Here, we made a gene catalog of 17 different microbial ecosystems and compared them. We show that most species shared between environment and human gut microbiomes are pathogens and that prior gene catalogs described as "nearly complete" are far from it. Additionally, over two-thirds of all genes only appear in a single sample, and only 1,864 genes (0.001%) are found in all types of metagenomes. These results highlight the large diversity between metagenomes and reveal a new, rare class of genes, those found in every type of metagenome, but not every microbial genome.}, }
@article {pmid37022154, year = {2023}, author = {Mahmud, MR and Jian, C and Uddin, MK and Huhtinen, M and Salonen, A and Peltoniemi, O and Venhoranta, H and Oliviero, C}, title = {Impact of Intestinal Microbiota on Growth Performance of Suckling and Weaned Piglets.}, journal = {Microbiology spectrum}, volume = {11}, number = {3}, pages = {e0374422}, pmid = {37022154}, issn = {2165-0497}, mesh = {Swine ; Animals ; Female ; Weaning ; *Gastrointestinal Microbiome/genetics ; RNA, Ribosomal, 16S/genetics ; Bacteria/genetics ; Feces/microbiology ; }, abstract = {Small-scale studies investigating the relationship between pigs' intestinal microbiota and growth performance have generated inconsistent results. We hypothesized that on farms under favorable environmental conditions (e.g., promoting sow nest-building behavior, high colostrum production, low incidence of diseases and minimal use of antimicrobials), the piglet gut microbiota may develop toward a population that promotes growth and reduces pathogenic bacteria. Using 16S rRNA gene amplicon sequencing, we sampled and profiled the fecal microbiota from 170 individual piglets throughout suckling and postweaning periods (in total 670 samples) to track gut microbiota development and its potential association with growth. During the suckling period, the dominant genera were Lactobacillus and Bacteroides, the latter being gradually replaced by Clostridium sensu scricto 1 as piglets aged. The gut microbiota during the nursery stage, not the suckling period, predicted the average daily growth (ADG) of piglets. The relative abundances of SCFA-producing genera, in particular Faecalibacterium, Megasphaera, Mitsuokella, and Subdoligranulum, significantly correlated with high ADG of weaned piglets. In addition, the succession of the gut microbiota in high-ADG piglets occurred faster and stabilized sooner upon weaning, whereas the gut microbiota of low-ADG piglets continued to mature after weaning. Overall, our findings suggest that weaning is the major driver of gut microbiota variation in piglets with different levels of overall growth performance. This calls for further research to verify if promotion of specific gut microbiota, identified here at weaning transition, is beneficial for piglet growth. IMPORTANCE The relationship between pigs' intestinal microbiota and growth performance is of great importance for improving piglets' health and reducing antimicrobial use. We found that gut microbiota variation is significantly associated with growth during weaning and the early nursery period. Importantly, transitions toward a mature gut microbiota enriched with fiber-degrading bacteria mostly complete upon weaning in piglets with better growth. Postponing the weaning age may therefore favor the development of fiber degrading gut bacteria, conferring the necessary capacity to digest and harvest solid postweaning feed. The bacterial taxa associated with piglet growth identified herein hold potential to improve piglet growth and health.}, }
@article {pmid37019665, year = {2023}, author = {Ka, Y and Ito, R and Nozu, R and Tomiyama, K and Ueno, M and Ogura, T and Takahashi, R}, title = {Establishment of a human microbiome- and immune system-reconstituted dual-humanized mouse model.}, journal = {Experimental animals}, volume = {72}, number = {3}, pages = {402-412}, pmid = {37019665}, issn = {1881-7122}, mesh = {Mice ; Animals ; Humans ; Mice, Inbred NOD ; *Immune System ; Hematopoietic Stem Cells ; Disease Models, Animal ; *Gastrointestinal Microbiome ; Mice, SCID ; }, abstract = {Humanized mice are widely used to study the human immune system in vivo and investigate therapeutic targets for various human diseases. Immunodeficient NOD/Shi-scid-IL2rγ[null] (NOG) mice transferred with human hematopoietic stem cells are a useful model for studying human immune systems and analyzing engrafted human immune cells. The gut microbiota plays a significant role in the development and function of immune cells and the maintenance of immune homeostasis; however, there is currently no available animal model that has been reconstituted with human gut microbiota and immune systems in vivo. In this study, we established a new model of CD34[+] cell-transferred humanized germ-free NOG mice using an aseptic method. Flow cytometric analysis revealed that the germ-free humanized mice exhibited a lower level of human CD3[+] T cells than the SPF humanized mice. Additionally, we found that the human CD3[+] T cells slightly increased after transplanting human gut microbiota into the germ-free humanized mice, suggesting that the human microbiota supports T cell proliferation or maintenance in humanized mice colonized by the gut microbiota. Consequently, the dual-humanized mice may be useful for investigating the physiological role of the gut microbiota in human immunity in vivo and for application as a new humanized mouse model in cancer immunology.}, }
@article {pmid37010974, year = {2023}, author = {Reynolds, T and Noorbakhsh, S and Smith, R}, title = {Microbiome Contributions to Health.}, journal = {Surgical infections}, volume = {24}, number = {3}, pages = {213-219}, pmid = {37010974}, issn = {1557-8674}, support = {T32 GM095442/GM/NIGMS NIH HHS/United States ; }, mesh = {Humans ; *Microbiota ; Gastrointestinal Tract/microbiology ; Lung ; Bacteria ; }, abstract = {The human microbiome is vast and is present in spaces previously thought to be sterile such as the lungs. A healthy microbiome is diverse and functions in an adaptive way to support local as well as organism health and function. Furthermore, a normal microbiome is essential for normal immune system development rendering the array of microbes that live in and on the human body key components of homeostasis. A wide array of clinical conditions and interventions including anesthesia, analgesia, and surgical intervention may derange the human microbiome in a maladaptive fashion with bacterial responses spanning decreased diversity to transformation to a pathogenic phenotype. Herein, we explore the normal microbiome of the skin, gastrointestinal tract, and the lungs as prototype sites to describe the influence of the microbiomes in each of those locations on health, and how care may derange those relations.}, }
@article {pmid37010972, year = {2023}, author = {Leonard, JM and Toro, DD}, title = {Defining the Microbiome Components (Bacteria, Viruses, Fungi) and Microbiome Geodiversity.}, journal = {Surgical infections}, volume = {24}, number = {3}, pages = {208-212}, pmid = {37010972}, issn = {1557-8674}, support = {K08 GM137323/GM/NIGMS NIH HHS/United States ; }, mesh = {Humans ; Bacteria ; *Microbiota/genetics ; Fungi ; *Viruses ; }, abstract = {The recognition that a resident community of microbes contributes substantially to human health and disease is one of the emerging great discoveries in modern medicine. This collection of bacteria, archaea, fungi, viruses, and eukaryotes are referred to as microbiota, which together with the individual tissues they inhabit is defined as our individual microbiome. Recent advances in modern DNA sequencing technologies permit the identification, description, and characterization of these microbial communities as well as their variations within and between individuals and groups. This complex understanding of the human microbiome is supported by a rapidly expanding field of inquiry and offers the potential to significantly impact the treatment of a wide variety of disease states. This review explores the recent findings associated with the various components of the human microbiome, and the geodiversity of microbial communities between different tissue types, individuals, and clinical conditions.}, }
@article {pmid37010971, year = {2023}, author = {Godley, FA and Shogan, BD and Hyman, NH}, title = {Role of the Microbiome in Malignancy.}, journal = {Surgical infections}, volume = {24}, number = {3}, pages = {271-275}, pmid = {37010971}, issn = {1557-8674}, support = {K08 CA248957/CA/NCI NIH HHS/United States ; }, mesh = {Female ; Humans ; *Microbiota ; *Colorectal Neoplasms ; Carcinogenesis ; Inflammation ; }, abstract = {The conceptual underpinning of carcinogenesis has been strongly influenced by an expanded understanding of the human microbiome. Malignancy risks in diverse organs have been uniquely tied to aspects of the resident microbiota in different organs and systems including the colon, lungs, pancreas, ovaries, uterine cervix, and stomach; other organs are increasingly linked to maladaptive aspects of the microbiome as well. In this way, the maladaptive microbiome may be termed an oncobiome. Microbe-driven inflammation, anti-inflammation, and mucosal protection failure, as well as diet-induced microbiome derangement are all mechanisms that influence malignancy risk. Therefore, they also offer potential avenues of diagnostic and therapeutic intervention to modify malignancy risk, and to perhaps interrupt progression toward cancer in different sites. Each of these mechanisms will be explored using colorectal malignancy as a prototype condition to demonstrate the microbiome's role in carcinogenesis.}, }
@article {pmid37010968, year = {2023}, author = {Leonard, JM and Pascual, JL and Kaplan, LJ}, title = {Dysbiome and Its Role in Surgically Relevant Medical Disease.}, journal = {Surgical infections}, volume = {24}, number = {3}, pages = {226-231}, pmid = {37010968}, issn = {1557-8674}, support = {K08 GM137323/GM/NIGMS NIH HHS/United States ; }, mesh = {Humans ; *Inflammatory Bowel Diseases ; *Microbiota ; *Gastrointestinal Microbiome ; Skin ; }, abstract = {Several surgically relevant conditions are directly or indirectly influenced by the human microbiome. Different microbiomes may be found within, or along, specific organs and intra-organ variation is common. Such variations include those found along the course of the gastrointestinal tract as well as those on different regions of the skin. A variety of physiologic stressors and care interventions may derange the native microbiome. A deranged microbiome is termed a dysbiome and is characterized by decreased diversity and an increase in the proportion of potentially pathogenic organisms; the elaboration of virulence factors coupled with clinical consequences defines a pathobiome. Specific conditions such as Clostridium difficile colitis, inflammatory bowel disease, obesity, and diabetes mellitus are tightly linked to a dysbiome or pathobiome. Additionally, massive transfusion after injury appears to derange the gastrointestinal microbiome as well. This review explores what is known about these surgically relevant clinical conditions to chart how non-surgical interventions may support surgical undertakings or potentially reduce the need for operation.}, }
@article {pmid37010965, year = {2023}, author = {Creel, JP and Maves, RC}, title = {The Microbiome and Antimicrobial Stewardship in Surgical Patients.}, journal = {Surgical infections}, volume = {24}, number = {3}, pages = {220-225}, doi = {10.1089/sur.2022.422}, pmid = {37010965}, issn = {1557-8674}, mesh = {Humans ; *Antimicrobial Stewardship ; *Anti-Infective Agents ; *Microbiota ; Anti-Bacterial Agents/therapeutic use ; *Clostridium Infections/drug therapy ; }, abstract = {Abstract The human microbiome plays a critical role in health and disease. The microbiota of the human body undergoes disruptions in critical illness, in part due to alterations in physiology but also as the result of medical interventions, most notably antimicrobial drug administration. These alterations may lead to a significant dysbiosis, with increased risks of multi-drug-resistant organism-based secondary infections, Clostridioides difficile promotion, and other infection-related complications. Antimicrobial stewardship is a process that seeks to optimize antimicrobial drug prescription, with recent evidence emphasizing shorter courses of therapy, earlier transitions from empiric to pathogen-specific regimens, and enhanced diagnostic testing. Through a combination of prudent stewardship and wise use of diagnostic testing, clinicians can improve outcomes, reduce the risk of antimicrobial resistance, and help improve the integrity of the microbiome.}, }
@article {pmid37005490, year = {2023}, author = {Goenka, A and Khan, F and Verma, B and Sinha, P and Dmello, CC and Jogalekar, MP and Gangadaran, P and Ahn, BC}, title = {Tumor microenvironment signaling and therapeutics in cancer progression.}, journal = {Cancer communications (London, England)}, volume = {43}, number = {5}, pages = {525-561}, pmid = {37005490}, issn = {2523-3548}, mesh = {Humans ; *Tumor Microenvironment ; *Neoplasms/metabolism ; Signal Transduction ; Neoplastic Processes ; Receptors, Chemokine/therapeutic use ; Chemokines/pharmacology/therapeutic use ; }, abstract = {Tumor development and metastasis are facilitated by the complex interactions between cancer cells and their microenvironment, which comprises stromal cells and extracellular matrix (ECM) components, among other factors. Stromal cells can adopt new phenotypes to promote tumor cell invasion. A deep understanding of the signaling pathways involved in cell-to-cell and cell-to-ECM interactions is needed to design effective intervention strategies that might interrupt these interactions. In this review, we describe the tumor microenvironment (TME) components and associated therapeutics. We discuss the clinical advances in the prevalent and newly discovered signaling pathways in the TME, the immune checkpoints and immunosuppressive chemokines, and currently used inhibitors targeting these pathways. These include both intrinsic and non-autonomous tumor cell signaling pathways in the TME: protein kinase C (PKC) signaling, Notch, and transforming growth factor (TGF-β) signaling, Endoplasmic Reticulum (ER) stress response, lactate signaling, Metabolic reprogramming, cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) and Siglec signaling pathways. We also discuss the recent advances in Programmed Cell Death Protein 1 (PD-1), Cytotoxic T-Lymphocyte Associated Protein 4 (CTLA4), T-cell immunoglobulin mucin-3 (TIM-3) and Lymphocyte Activating Gene 3 (LAG3) immune checkpoint inhibitors along with the C-C chemokine receptor 4 (CCR4)- C-C class chemokines 22 (CCL22)/ and 17 (CCL17), C-C chemokine receptor type 2 (CCR2)- chemokine (C-C motif) ligand 2 (CCL2), C-C chemokine receptor type 5 (CCR5)- chemokine (C-C motif) ligand 3 (CCL3) chemokine signaling axis in the TME. In addition, this review provides a holistic understanding of the TME as we discuss the three-dimensional and microfluidic models of the TME, which are believed to recapitulate the original characteristics of the patient tumor and hence may be used as a platform to study new mechanisms and screen for various anti-cancer therapies. We further discuss the systemic influences of gut microbiota in TME reprogramming and treatment response. Overall, this review provides a comprehensive analysis of the diverse and most critical signaling pathways in the TME, highlighting the associated newest and critical preclinical and clinical studies along with their underlying biology. We highlight the importance of the most recent technologies of microfluidics and lab-on-chip models for TME research and also present an overview of extrinsic factors, such as the inhabitant human microbiome, which have the potential to modulate TME biology and drug responses.}, }
@article {pmid37003965, year = {2023}, author = {Syama, K and Jothi, JAA and Khanna, N}, title = {Automatic disease prediction from human gut metagenomic data using boosting GraphSAGE.}, journal = {BMC bioinformatics}, volume = {24}, number = {1}, pages = {126}, pmid = {37003965}, issn = {1471-2105}, mesh = {Humans ; Metagenome ; *Microbiota/genetics ; Machine Learning ; Metagenomics/methods ; *Inflammatory Bowel Diseases/genetics ; *Colorectal Neoplasms/genetics ; }, abstract = {BACKGROUND: The human microbiome plays a critical role in maintaining human health. Due to the recent advances in high-throughput sequencing technologies, the microbiome profiles present in the human body have become publicly available. Hence, many works have been done to analyze human microbiome profiles. These works have identified that different microbiome profiles are present in healthy and sick individuals for different diseases. Recently, several computational methods have utilized the microbiome profiles to automatically diagnose and classify the host phenotype.<br><br>RESULTS: In this work, a novel deep learning framework based on boosting GraphSAGE is proposed for automatic prediction of diseases from metagenomic data. The proposed framework has two main components, (a). Metagenomic Disease graph (MD-graph) construction module, (b). Disease prediction Network (DP-Net) module. The graph construction module constructs a graph by considering each metagenomic sample as a node in the graph. The graph captures the relationship between the samples using a proximity measure. The DP-Net consists of a boosting GraphSAGE model which predicts the status of a sample as sick or healthy. The effectiveness of the proposed method is verified using real and synthetic datasets corresponding to diseases like inflammatory bowel disease and colorectal cancer. The proposed model achieved a highest AUC of 93%, Accuracy of 95%, F1-score of 95%, AUPRC of 95% for the real inflammatory bowel disease dataset and a best AUC of 90%, Accuracy of 91%, F1-score of 87% and AUPRC of 93% for the real colorectal cancer dataset.<br><br>CONCLUSION: The proposed framework outperforms other machine learning and deep learning models in terms of classification accuracy, AUC, F1-score and AUPRC for both synthetic and real metagenomic data.}, }
@article {pmid37002975, year = {2023}, author = {Stockdale, SR and Hill, C}, title = {Incorporating plasmid biology and metagenomics into a holistic model of the human gut microbiome.}, journal = {Current opinion in microbiology}, volume = {73}, number = {}, pages = {102307}, doi = {10.1016/j.mib.2023.102307}, pmid = {37002975}, issn = {1879-0364}, mesh = {Humans ; *Gastrointestinal Microbiome/genetics ; Plasmids/genetics ; *Microbiota/genetics ; Bacteria/genetics ; Metagenomics ; }, abstract = {The human gut microbiome is often described as the collection of bacteria, archaea, fungi, protists, and viruses associated with an individual, with no acknowledgement of the plasmid constituents. However, like viruses, plasmids are autonomous intracellular replicating entities that can influence the genotype and phenotype of their host and mediate trans-kingdom interactions. Plasmids are frequently noted as vehicles for horizontal gene transfer and for spreading antibiotic resistance, yet their multifaceted contribution to mutualistic and antagonistic interactions within the human microbiome and impact on human health is overlooked. In this review, we highlight the importance of plasmids and their biological properties as overlooked components of microbiomes. Subsequent human microbiome studies should include dedicated analyses of plasmids, particularly as a holistic understanding of human-microbial interactions is required before effective and safe interventions can be implemented to improve human well-being.}, }
@article {pmid36998574, year = {2023}, author = {Haahtela, T and Alenius, H and Auvinen, P and Fyhrquist, N and von Hertzen, L and Jousilahti, P and Karisola, P and Laatikainen, T and Lehtimäki, J and Paalanen, L and Ruokolainen, L and Saarinen, K and Valovirta, E and Vasankari, T and Vlasoff, T and Erhola, M and Bousquet, J and Vartiainen, E and Mäkelä, MJ}, title = {A short history from Karelia study to biodiversity and public health interventions.}, journal = {Frontiers in allergy}, volume = {4}, number = {}, pages = {1152927}, pmid = {36998574}, issn = {2673-6101}, abstract = {Contact with natural environments enriches the human microbiome, promotes immune balance and protects against allergies and inflammatory disorders. In Finland, the allergy &amp; asthma epidemic became slowly visible in mid 1960s. After the World War II, Karelia was split into Finnish and Soviet Union (now Russia) territories. This led to more marked environmental and lifestyle changes in the Finnish compared with Russian Karelia. The Karelia Allergy Study 2002-2022 showed that allergic conditions were much more common on the Finnish side. The Russians had richer gene-microbe network and interaction than the Finns, which associated with better balanced immune regulatory circuits and lower allergy prevalence. In the Finnish adolescents, a biodiverse natural environment around the homes associated with lower occurrence of allergies. Overall, the plausible explanation of the allergy disparity was the prominent change in environment and lifestyle in the Finnish Karelia from 1940s to 1980s. The nationwide Finnish Allergy Programme 2008-2018 implemented the biodiversity hypothesis into practice by endorsing immune tolerance, nature contacts, and allergy health with favorable results. A regional health and environment programme, Nature Step to Health 2022-2032, has been initiated in the City of Lahti, EU Green Capital 2021. The programme integrates prevention of chronic diseases (asthma, diabetes, obesity, depression), nature loss, and climate crisis in the spirit of Planetary Health. Allergic diseases exemplify inappropriate immunological responses to natural environment. Successful management of the epidemics of allergy and other non-communicable diseases may pave the way to improve human and environmental health.}, }
@article {pmid39295904, year = {2023}, author = {Ruxton, CHS and Kajita, C and Rocca, P and Pot, B}, title = {Microbiota and probiotics: chances and challenges - a symposium report.}, journal = {Gut microbiome (Cambridge, England)}, volume = {4}, number = {}, pages = {e6}, pmid = {39295904}, issn = {2632-2897}, abstract = {The 10th International Yakult Symposium was held in Milan, Italy, on 13-14 October 2022. Two keynote lectures covered the crewed journey to space and its implications for the human microbiome, and how current regulatory systems can be adapted and updated to ensure the safety of microorganisms used as probiotics or food processing ingredients. The remaining lectures were split into sections entitled "Chances" and "Challenges." The "Chances" section explored opportunities for the science of probiotics and fermented foods to contribute to diverse areas of health such as irritable bowel syndrome, major depression, Parkinson's disease, immune dysfunction, infant colic, intensive care, respiratory infections, and promoting healthy longevity. The "Challenges" section included selecting appropriate clinical trial participants and methodologies to minimise heterogeneity in responses, how to view probiotics in the context of One Health, adapting regulatory frameworks, and understanding how substances of bacterial origin can cross the blood-brain barrier. The symposium provided evidence from cutting-edge research that gut eubiosis is vital for human health and, like space, the microbiota deserves further exploration of its vast potential.}, }
@article {pmid39295911, year = {2023}, author = {Panwar, S and Kumari, S and Verma, J and Bakshi, S and Narendrakumar, L and Paul, D and Das, B}, title = {Toxin-linked mobile genetic elements in major enteric bacterial pathogens.}, journal = {Gut microbiome (Cambridge, England)}, volume = {4}, number = {}, pages = {e5}, pmid = {39295911}, issn = {2632-2897}, abstract = {One of the fascinating outcomes of human microbiome studies adopting multi-omics technology is its ability to decipher millions of microbial encoded functions in the most complex and crowded microbial ecosystem, including the human gastrointestinal (GI) tract without cultivating the microbes. It is well established that several functions that modulate the human metabolism, nutrient assimilation, immunity, infections, disease severity and therapeutic efficacy of drugs are mostly of microbial origins. In addition, these microbial functions are dynamic and can disseminate between microbial taxa residing in the same ecosystem or other microbial ecosystems through horizontal gene transfer. For clinicians and researchers alike, understanding the toxins, virulence factors and drug resistance traits encoded by the microbes associated with the human body is of utmost importance. Nevertheless, when such traits are genetically linked with mobile genetic elements (MGEs) that make them transmissible, it creates an additional burden to public health. This review mainly focuses on the functions of gut commensals and the dynamics and crosstalk between commensal and pathogenic bacteria in the gut. Also, the review summarises the plethora of MGEs linked with virulence genes present in the genomes of various enteric bacterial pathogens, which are transmissible among other pathogens and commensals.}, }
@article {pmid38550941, year = {2023}, author = {Ellinghaus, D}, title = {COVID-19 host genetics and ABO blood group susceptibility.}, journal = {Cambridge prisms. Precision medicine}, volume = {1}, number = {}, pages = {e10}, pmid = {38550941}, issn = {2752-6143}, abstract = {Twenty-five susceptibility loci for SARS-CoV-2 infection and/or COVID-19 disease severity have been identified in the human genome by genome-wide association studies, and the most frequently replicated genetic findings for susceptibility are genetic variants at the ABO gene locus on chromosome 9q34.2, which is supported by the association between ABO blood group distribution and COVID-19. The ABO blood group effect appears to influence a variety of disease conditions and pathophysiological mechanisms associated with COVID-19. Transmission models for SARS-CoV-2 combined with observational public health and genome-wide data from patients and controls, as well as receptor binding experiments in cell lines and human samples, indicate that there may be a reduction or slowing of infection events by up to 60% in certain ABO blood group constellations of index and contact person in the early phase of a SARS-CoV-2 outbreak. The strength of the ABO blood group effect on reducing infection rates further depends on the distribution of the ABO blood groups in the respective population and the proportion of blood group O in that population. To understand in detail the effect of ABO blood groups on COVID-19, further studies are needed in relation to different demographic characteristics, but also in relation to recent data on reinfection with new viral variants and in the context of the human microbiome.}, }
@article {pmid38867907, year = {2022}, author = {Ma, Y and Ke, D and Li, D and Zhang, Q}, title = {Donors' experiences and attitudes of fecal microbiota transplantation: An empirical bioethics study from China.}, journal = {iMeta}, volume = {1}, number = {4}, pages = {e62}, pmid = {38867907}, issn = {2770-596X}, abstract = {Donor participation is a critical part of ensuring the development of human microbiome research and the clinical application of fecal microbiota transplantation (FMT). Most FMT donors are still not sufficiently aware of the risks associated with the act of donating gut microbiota, especially the risk of data privacy disclosure. Enhanced awareness of the moral responsibility of the researchers and ethical oversight by ethics committees are needed.}, }
@article {pmid39628703, year = {2022}, author = {Liu, D and Siguenza, NE and Zarrinpar, A and Ding, Y}, title = {Methods of DNA introduction for the engineering of commensal microbes.}, journal = {Engineering microbiology}, volume = {2}, number = {4}, pages = {100048}, pmid = {39628703}, issn = {2667-3703}, support = {R01 EB030134/EB/NIBIB NIH HHS/United States ; UL1 TR001442/TR/NCATS NIH HHS/United States ; P30 DK120515/DK/NIDDK NIH HHS/United States ; P30 DK063491/DK/NIDDK NIH HHS/United States ; P50 AA011999/AA/NIAAA NIH HHS/United States ; U01 CA265719/CA/NCI NIH HHS/United States ; P30 CA014195/CA/NCI NIH HHS/United States ; }, abstract = {The microbiome is an essential component of ecological systems and is comprised of a diverse array of microbes. Over the past decades, the accumulated observational evidence reveals a close correlation between the microbiome and human health and disease. Many groups are now manipulating individual microbial strains, species and the community as a whole to gain a mechanistic understanding of the functions of the microbiome. Here, we discuss three major approaches for introducing DNA to engineer model bacteria and isolated undomesticated bacteria, including transformation, transduction, and conjugation. We provide an overview of these approaches and describe the advantages and limitations of each method. In addition, we highlight examples of human microbiome engineering using these approaches. Finally, we provide perspectives for the future of microbiome engineering.}, }
@article {pmid37850145, year = {2022}, author = {Cochrane, RR and Shrestha, A and Severo de Almeida, MM and Agyare-Tabbi, M and Brumwell, SL and Hamadache, S and Meaney, JS and Nucifora, DP and Say, HH and Sharma, J and Soltysiak, MPM and Tong, C and Van Belois, K and Walker, EJL and Lachance, MA and Gloor, GB and Edgell, DR and Shapiro, RS and Karas, BJ}, title = {Superior Conjugative Plasmids Delivered by Bacteria to Diverse Fungi.}, journal = {Biodesign research}, volume = {2022}, number = {}, pages = {9802168}, pmid = {37850145}, issn = {2693-1257}, abstract = {Fungi are nature's recyclers, allowing for ecological nutrient cycling and, in turn, the continuation of life on Earth. Some fungi inhabit the human microbiome where they can provide health benefits, while others are opportunistic pathogens that can cause disease. Yeasts, members of the fungal kingdom, have been domesticated by humans for the production of beer, bread, and, recently, medicine and chemicals. Still, the great untapped potential exists within the diverse fungal kingdom. However, many yeasts are intractable, preventing their use in biotechnology or in the development of novel treatments for pathogenic fungi. Therefore, as a first step for the domestication of new fungi, an efficient DNA delivery method needs to be developed. Here, we report the creation of superior conjugative plasmids and demonstrate their transfer via conjugation from bacteria to 7 diverse yeast species including the emerging pathogen Candida auris. To create our superior plasmids, derivatives of the 57 kb conjugative plasmid pTA-Mob 2.0 were built using designed gene deletions and insertions, as well as some unintentional mutations. Specifically, a cluster mutation in the promoter of the conjugative gene traJ had the most significant effect on improving conjugation to yeasts. In addition, we created Golden Gate assembly-compatible plasmid derivatives that allow for the generation of custom plasmids to enable the rapid insertion of designer genetic cassettes. Finally, we demonstrated that designer conjugative plasmids harboring engineered restriction endonucleases can be used as a novel antifungal agent, with important applications for the development of next-generation antifungal therapeutics.}, }
@article {pmid38046357, year = {2022}, author = {Aguanno, D and Metwaly, A and Coleman, OI and Haller, D}, title = {Modeling microbiota-associated human diseases: from minimal models to complex systems.}, journal = {Microbiome research reports}, volume = {1}, number = {3}, pages = {17}, pmid = {38046357}, issn = {2771-5965}, abstract = {Alterations in the intestinal microbiota are associated with various human diseases of the digestive system, including obesity and its associated metabolic diseases, inflammatory bowel diseases (IBD), and colorectal cancer (CRC). All three diseases are characterized by modifications of the richness, composition, and metabolic functions of the human intestinal microbiota. Despite being multi-factorial diseases, studies in germ-free animal models have unarguably identified the intestinal microbiota as a causal driver of disease pathogenesis. However, for an increased mechanistic understanding of microbial signatures in human diseases, models require detailed refinement to closely mimic the human microbiota and reflect the complexity and range of dysbiosis observed in patients. The transplantation of human fecal microbiota into animal models represents a powerful tool for studying the causal and functional role of the dysbiotic human microbiome in a pathological context. While human microbiota-associated models were initially employed to study obesity, an increasing number of studies have applied this approach in the context of IBD and CRC over the past decade. In this review, we discuss different approaches that allow the functional validation of the bacterial contribution to human diseases, with emphasis on obesity and its associated metabolic diseases, IBD, and CRC. We discuss the utility of simple models, such as in vitro fermentation systems of the human microbiota and ex vivo intestinal organoids, as well as more complex whole organism models. Our focus here lies on human microbiota-associated mouse models in the context of all three diseases, as well as highlighting the advantages and limitations of this approach.}, }
@article {pmid39295776, year = {2022}, author = {Puhlmann, ML and Jokela, R and van Dongen, KCW and Bui, TPN and van Hangelbroek, RWJ and Smidt, H and de Vos, WM and Feskens, EJM}, title = {Dried chicory root improves bowel function, benefits intestinal microbial trophic chains and increases faecal and circulating short chain fatty acids in subjects at risk for type 2 diabetes.}, journal = {Gut microbiome (Cambridge, England)}, volume = {3}, number = {}, pages = {e4}, pmid = {39295776}, issn = {2632-2897}, abstract = {We investigated the impact of dried chicory root in a randomised, placebo-controlled trial with 55 subjects at risk for type 2 diabetes on bowel function, gut microbiota and its products, and glucose homeostasis. The treatment increased stool softness (+1.1 ± 0.3 units; p = 0.034) and frequency (+0.6 ± 0.2 defecations/day; p < 0.001), strongly modulated gut microbiota composition (7 % variation; p = 0.001), and dramatically increased relative levels (3-4-fold) of Anaerostipes and Bifidobacterium spp., in a dose-dependent, reversible manner. A synthetic community, including selected members of these genera and a Bacteroides strain, generated a butyrogenic trophic chain from the product. Faecal acetate, propionate and butyrate increased by 25.8 % (+13.0 ± 6.3 mmol/kg; p = 0.023) as did their fasting circulating levels by 15.7 % (+7.7 ± 3.9 μM; p = 0.057). In the treatment group the glycaemic coefficient of variation decreased from 21.3 ± 0.94 to 18.3 ± 0.84 % (p = 0.004), whereas fasting glucose and HOMA-ir decreased in subjects with low baseline Blautia levels (-0.3 ± 0.1 mmol/L fasting glucose; p = 0.0187; -0.14 ± 0.1 HOMA-ir; p = 0.045). Dried chicory root intake rapidly and reversibly affects bowel function, benefits butyrogenic trophic chains, and promotes glycaemic control.}, }
@article {pmid37938295, year = {2022}, author = {Sanchez-Cid, C and Guironnet, A and Keuschnig, C and Wiest, L and Vulliet, E and Vogel, TM}, title = {Gentamicin at sub-inhibitory concentrations selects for antibiotic resistance in the environment.}, journal = {ISME communications}, volume = {2}, number = {1}, pages = {29}, pmid = {37938295}, issn = {2730-6151}, abstract = {Antibiotics released into the environment at low (sub-inhibitory) concentrations could select for antibiotic resistance that might disseminate to the human microbiome. In this case, low-level anthropogenic sources of antibiotics would have a significant impact on human health risk. In order to provide data necessary for the evaluation of this risk, we implemented river water microcosms at both sub-inhibitory and inhibitory concentrations of gentamicin as determined previously based on bacterial growth in enriched media. Using metagenomic sequencing and qPCR/RT-qPCR, we assessed the effects of gentamicin on water bacterial communities and their resistome. A change in the composition of total and active communities, as well as a gentamicin resistance gene selection identified via mobile genetic elements, was observed during a two-day exposure. We demonstrated the effects of sub-inhibitory concentrations of gentamicin on bacterial communities and their associated resistome in microcosms (simulating in situ conditions). In addition, we established relationships between antibiotic dose and the magnitude of the community response in the environment. The scope of resistance selection under sub-inhibitory concentrations of antibiotics and the mechanisms underlying this process might provide the basis for understanding resistance dispersion and associated risks in relatively low impacted ecosystems.}, }
@article {pmid37462964, year = {2022}, author = {Kong, XB and Dong, ZL and Wang, ZP}, title = {[Human microbiome and chronic prostatitis / chronic pelvic pain syndrome: An update].}, journal = {Zhonghua nan ke xue = National journal of andrology}, volume = {28}, number = {3}, pages = {243-246}, pmid = {37462964}, issn = {1009-3591}, mesh = {Male ; Humans ; Chronic Disease ; *Prostatitis ; Pelvic Pain ; *Microbiota ; *Chronic Pain ; }, abstract = {The significance of symbiotic microorganisms in the human body was recognized with the advancing of the concept of human microbiome and the development of related studies and technologies. These microorganisms play important roles in metabolism, immune regulation, the maintenance of health, and the development and progression of diseases in the human body. Recent studies show that chronic prostatitis / chronic pelvic pain syndrome (CP/CPPS) is related with human microbiome, mainly involving the urogenital tract, intestinal canal, and oral cavity. This review summarizes the studies on the relationship between the human microbiome and CP/CPPS in recent years.}, }
@article {pmid38993286, year = {2022}, author = {Reynoso-García, J and Miranda-Santiago, AE and Meléndez-Vázquez, NM and Acosta-Pagán, K and Sánchez-Rosado, M and Díaz-Rivera, J and Rosado-Quiñones, AM and Acevedo-Márquez, L and Cruz-Roldán, L and Tosado-Rodríguez, EL and Figueroa-Gispert, MDM and Godoy-Vitorino, F}, title = {A complete guide to human microbiomes: Body niches, transmission, development, dysbiosis, and restoration.}, journal = {Frontiers in systems biology}, volume = {2}, number = {}, pages = {}, pmid = {38993286}, issn = {2674-0702}, support = {U54 MD007600/MD/NIMHD NIH HHS/United States ; P20 GM103475/GM/NIGMS NIH HHS/United States ; U54 CA096297/CA/NCI NIH HHS/United States ; R25 GM061838/GM/NIGMS NIH HHS/United States ; U54 MD007587/MD/NIMHD NIH HHS/United States ; S21 MD001830/MD/NIMHD NIH HHS/United States ; R25 GM061151/GM/NIGMS NIH HHS/United States ; }, abstract = {Humans are supra-organisms co-evolved with microbial communities (Prokaryotic and Eukaryotic), named the microbiome. These microbiomes supply essential ecosystem services that play critical roles in human health. A loss of indigenous microbes through modern lifestyles leads to microbial extinctions, associated with many diseases and epidemics. This narrative review conforms a complete guide to the human holobiont-comprising the host and all its symbiont populations- summarizes the latest and most significant research findings in human microbiome. It pretends to be a comprehensive resource in the field, describing all human body niches and their dominant microbial taxa while discussing common perturbations on microbial homeostasis, impacts of urbanization and restoration and humanitarian efforts to preserve good microbes from extinction.}, }
@article {pmid37181836, year = {2022}, author = {Tochilina, AG and Belova, IV and Ilyicheva, TN and Marchenko, VY and Zhirnov, VA and Molodtsova, SB and Ikonnikov, AV and Muhkina, IV and Blagonravova, AS and Soloveva, IV}, title = {Genome Features of Probiotic Bifidobacteria Determining Their Strain-Specific Properties.}, journal = {Sovremennye tekhnologii v meditsine}, volume = {14}, number = {5}, pages = {36-43}, pmid = {37181836}, issn = {2309-995X}, mesh = {Animals ; Dogs ; Humans ; Bifidobacterium/genetics ; *Influenza A Virus, H1N1 Subtype ; *Influenza, Human ; Tryptophan ; *Probiotics/pharmacology ; *Bifidobacterium bifidum/physiology ; *Bacteriocins ; Antiviral Agents ; Folic Acid ; }, abstract = {UNLABELLED: The aim of the study was to analyze the genome features of the probiotic strains Bifidobacterium longum 379, Bifidobacterium bifidum 1, and Bifidobacterium bifidum 791 and study their antiviral activity.<br><br>MATERIALS AND METHODS: Whole genome sequencing of three strains of bifidobacteria was performed on the MiSeq platform (Illumina Inc., USA). The genomes were annotated using the Prokka v. 1.11 utility and RAST genomic server. The individual genetic determinants were searched using the ResFinder 3.2, PathogenFinder, PlasmidFinder, RAST, and Bagel 4 software. The antiviral activity of the strains against influenza A viruses was studied using MDCK cells (Madin-Darby canine kidney cells), the epidemic strain of influenza A/Lipetsk/1V/2018 (H1N1 pdm09) (EPI_ISL_332798), the highly pathogenic avian influenza virus A/common gull/Saratov/1676/2018 (H5N6) strain (EPI_ISL_336925), and neutral red vital dye.<br><br>RESULTS: The genomes of all studied strains contained determinants responsible for utilization of carbohydrates of plant origin; the genes of key enzymes for the synthesis of tryptophan and folic acid are present in the genomes of B. longum 379 and B. bifidum 791. A feature of the B. bifidum 791 genome is the presence of determinants responsible for the synthesis of thermostable type I bacteriocins - flavucin and lasso peptide. The B. bifidum 791 strain was found to show pronounced antiviral activity against both the strains of influenza A, the supernatant of which suppressed viral replication in vitro up to a dilution of 1:8, and the cells inhibited viral reproduction up to a concentration of 6&#xb7;106 CFU/ml.<br><br>CONCLUSION: The analysis of complete genomes of B. longum 379, B. bifidum 1, and B. bifidum 791 showed features that determine their strain-specific properties, the findings on which were previously made empirically based on indirect signs. In the genomes of B. longum 379 and B. bifidum 791 strains, in contrast to B. bifidum 1 strain, key enzymes for the synthesis of tryptophan and folic acid were found. These substances have an impact on the human body in many ways, including having a thymoleptic effect (reducing emotional stress, irritability, anxiety, eliminating lethargy, apathy, melancholy, anxiety) and regulating cognitive activity. The presence of determinants responsible for the synthesis of thermostable type I bacteriocins in the genome of B. bifidum 791 strain determines its pronounced antiviral activity.}, }
@article {pmid37938646, year = {2021}, author = {Mayerhofer, MM and Eigemann, F and Lackner, C and Hoffmann, J and Hellweger, FL}, title = {Dynamic carbon flux network of a diverse marine microbial community.}, journal = {ISME communications}, volume = {1}, number = {1}, pages = {50}, pmid = {37938646}, issn = {2730-6151}, abstract = {The functioning of microbial ecosystems has important consequences from global climate to human health, but quantitative mechanistic understanding remains elusive. The components of microbial ecosystems can now be observed at high resolution, but interactions still have to be inferred e.g., a time-series may show a bloom of bacteria X followed by virus Y suggesting they interact. Existing inference approaches are mostly empirical, like correlation networks, which are not mechanistically constrained and do not provide quantitative mass fluxes, and thus have limited utility. We developed an inference method, where a mechanistic model with hundreds of species and thousands of parameters is calibrated to time series data. The large scale, nonlinearity and feedbacks pose a challenging optimization problem, which is overcome using a novel procedure that mimics natural speciation or diversification e.g., stepwise increase of bacteria species. The method allows for curation using species-level information from e.g., physiological experiments or genome sequences. The product is a mass-balancing, mechanistically-constrained, quantitative representation of the ecosystem. We apply the method to characterize phytoplankton-heterotrophic bacteria interactions via dissolved organic matter in a marine system. The resulting model predicts quantitative fluxes for each interaction and time point (e.g., 0.16 µmolC/L/d of chrysolaminarin to Polaribacter on April 16, 2009). At the system level, the flux network shows a strong correlation between the abundance of bacteria species and their carbon flux during blooms, with copiotrophs being relatively more important than oligotrophs. However, oligotrophs, like SAR11, are unexpectedly high carbon processors for weeks into blooms, due to their higher biomass. The fraction of exudates (vs. grazing/death products) in the DOM pool decreases during blooms, and they are preferentially consumed by oligotrophs. In addition, functional similarity of phytoplankton i.e., what they produce, decouples their association with heterotrophs. The methodology is applicable to other microbial ecosystems, like human microbiome or wastewater treatment plants.}, }
@article {pmid37440868, year = {2021}, author = {Shuler, K and Verbanic, S and Chen, IA and Lee, J}, title = {A Bayesian nonparametric analysis for zero-inflated multivariate count data with application to microbiome study.}, journal = {Journal of the Royal Statistical Society. Series C, Applied statistics}, volume = {70}, number = {4}, pages = {961-979}, pmid = {37440868}, issn = {0035-9254}, support = {DP2 GM123457/GM/NIGMS NIH HHS/United States ; }, abstract = {High-throughput sequencing technology has enabled researchers to profile microbial communities from a variety of environments, but analysis of multivariate taxon count data remains challenging. We develop a Bayesian nonparametric (BNP) regression model with zero inflation to analyse multivariate count data from microbiome studies. A BNP approach flexibly models microbial associations with covariates, such as environmental factors and clinical characteristics. The model produces estimates for probability distributions which relate microbial diversity and differential abundance to covariates, and facilitates community comparisons beyond those provided by simple statistical tests. We compare the model to simpler models and popular alternatives in simulation studies, showing, in addition to these additional community-level insights, it yields superior parameter estimates and model fit in various settings. The model's utility is demonstrated by applying it to a chronic wound microbiome data set and a Human Microbiome Project data set, where it is used to compare microbial communities present in different environments.}, }
@article {pmid37333953, year = {2020}, author = {Wilcox, H and Carr, C and Seney, S and Reid, G and Burton, JP}, title = {Expired probiotics: what is really in your cabinet?.}, journal = {FEMS microbes}, volume = {1}, number = {1}, pages = {xtaa007}, pmid = {37333953}, issn = {2633-6685}, abstract = {The popularity of using probiotics has surged, since they became widely accepted as safe and help improve general health. Inevitably, some of these products are used after expiration when microbial cell viability is below the recommended effective dose. Given that probiotics must be live microorganisms administered in adequate amounts, the aim of this study was to measure viability in expired products and assess how packaging and storage conditions impact efficacy, if at all. Thirty-three expired probiotic products were evaluated, of which 26 were stored in conditions recommended by the manufacturer. The viable microbial cells were enumerated and representative isolates identified by 16S and internally transcribed spacer rRNA gene sequencing. While the products had a mean past expiration time of 11.32 (1-22) years, 22 still had viable contents, and 5 were within or above the original product cell count claim. Product formulation and the number of species present did not appear to impact the stability of the products. However, overall packaging type, storage conditions and time since expiry were found to affect viability. All products with viable cells had the strain stipulated on the label. Despite some selected probiotic products retaining viability past their expiry date (indicating long-term storage is possible), the total counts were mostly well below that required for efficacious use as recommended by the manufacturer. Consuming expired probiotics may not yield the benefits for which they were designed.}, }
@article {pmid39296724, year = {2020}, author = {Hill, C}, title = {You have the microbiome you deserve.}, journal = {Gut microbiome (Cambridge, England)}, volume = {1}, number = {}, pages = {e3}, pmid = {39296724}, issn = {2632-2897}, abstract = {The human microbiome is one of the most exciting areas of microbiology. From a starting point of tens of papers annually a couple of decades ago, there are now thousands of papers published every year on the microbiome. Huge strides have been made in terms of defining the individual members of complex human microbiomes from different body sites. The individuality and diversity of the human microbiome almost surpasses our ability to comprehend it. Advances in metagenomics and computational sciences have increased the complexity of the field, while at the same time we have moved from regarding the human microbiome as a benign passenger to a situation where it has been linked to almost every chronic disease, including obesity, cancer and infectious disease. The microbiome tantalizes us with the promise of novel therapeutic molecules and modalities for a range of intractable diseases. And yet, very few microbiome-based therapies have made it to the clinic or the pharmacy and we still cannot really define a healthy microbiome. We are entering the most exciting phase of microbiome research, as we develop effective, evidence-based interventions to preserve and restore human health. But we need rigour and numeracy if we are to realize this vision.}, }
@article {pmid36995244, year = {2023}, author = {Herviou, P and Balvay, A and Bellet, D and Bobet, S and Maudet, C and Staub, J and Alric, M and Leblond-Bourget, N and Delorme, C and Rabot, S and Denis, S and Payot, S}, title = {Transfer of the Integrative and Conjugative Element ICESt3 of Streptococcus thermophilus in Physiological Conditions Mimicking the Human Digestive Ecosystem.}, journal = {Microbiology spectrum}, volume = {11}, number = {3}, pages = {e0466722}, pmid = {36995244}, issn = {2165-0497}, mesh = {Animals ; Mice ; Humans ; *Streptococcus thermophilus/genetics ; Conjugation, Genetic ; Gastrointestinal Tract ; Gene Transfer, Horizontal ; *Microbiota ; }, abstract = {Metagenome analyses of the human microbiome suggest that horizontal gene transfer (HGT) is frequent in these rich and complex microbial communities. However, so far, only a few HGT studies have been conducted in vivo. In this work, three different systems mimicking the physiological conditions encountered in the human digestive tract were tested, including (i) the TNO gastro-Intestinal tract Model 1 (TIM-1) system (for the upper part of the intestine), (ii) the ARtificial COLon (ARCOL) system (to mimic the colon), and (iii) a mouse model. To increase the likelihood of transfer by conjugation of the integrative and conjugative element studied in the artificial digestive systems, bacteria were entrapped in alginate, agar, and chitosan beads before being placed in the different gut compartments. The number of transconjugants detected decreased, while the complexity of the ecosystem increased (many clones in TIM-1 but only one clone in ARCOL). No clone was obtained in a natural digestive environment (germfree mouse model). In the human gut, the richness and diversity of the bacterial community would offer more opportunities for HGT events to occur. In addition, several factors (SOS-inducing agents, microbiota-derived factors) that potentially increase in vivo HGT efficiency were not tested here. Even if HGT events are rare, expansion of the transconjugant clones can happen if ecological success is fostered by selecting conditions or by events that destabilize the microbial community. IMPORTANCE The human gut microbiota plays a key role in maintaining normal host physiology and health, but its homeostasis is fragile. During their transit in the gastrointestinal tract, bacteria conveyed by food can exchange genes with resident bacteria. New traits acquired by HGT (e.g., new catabolic properties, bacteriocins, antibiotic resistance) can impact the gut microbial composition and metabolic potential. We showed here that TIM-1, a system mimicking the upper digestive tract, is a useful tool to evaluate HGT events in conditions closer to the physiological ones. Another important fact pointed out in this work is that Enterococcus faecalis is a good candidate for foreign gene acquisition. Due to its high ability to colonize the gut and acquire mobile genetic elements, this commensal bacterium could serve as an intermediate for HGT in the human gut.}, }
@article {pmid36992511, year = {2023}, author = {Shafigh Kheljan, F and Sheikhzadeh Hesari, F and Aminifazl, MS and Skurnik, M and Goladze, S and Zarrini, G}, title = {Design of Phage-Cocktail-Containing Hydrogel for the Treatment of Pseudomonas aeruginosa-Infected Wounds.}, journal = {Viruses}, volume = {15}, number = {3}, pages = {}, pmid = {36992511}, issn = {1999-4915}, mesh = {Mice ; Animals ; *Bacteriophages ; Pseudomonas aeruginosa ; Hydrogels/pharmacology/therapeutic use ; Anti-Bacterial Agents/pharmacology/therapeutic use ; Ciprofloxacin/pharmacology ; *Bacterial Infections/drug therapy ; Disease Models, Animal ; *Wound Infection/drug therapy ; }, abstract = {Recently, the treatment of infected wounds has become a global problem due to increased antibiotic resistance in bacteria. The Gram-negative opportunistic pathogen Pseudomonas aeruginosa is often present in chronic skin infections, and it has become a threat to public health as it is increasingly multidrug resistant. Due to this, new measures to enable treatment of infections are necessary. Treatment of bacterial infections with bacteriophages, known as phage therapy, has been in use for a century, and has potential with its antimicrobial effect. The main purpose of this study was to create a phage-containing wound dressing with the ability to prevent bacterial infection and rapid wound healing without side effects. Several phages against P. aeruginosa were isolated from wastewater, and two polyvalent phages were used to prepare a phage cocktail. The phage cocktail was loaded in a hydrogel composed of polymers of sodium alginate (SA) and carboxymethyl cellulose (CMC). To compare the antimicrobial effects, hydrogels containing phages, ciprofloxacin, or phages plus ciprofloxacin were produced, and hydrogels without either. The antimicrobial effect of these hydrogels was investigated in vitro and in vivo using an experimental mouse wound infection model. The wound-healing process in different mouse groups showed that phage-containing hydrogels and antibiotic-containing hydrogels have almost the same antimicrobial effect. However, in terms of wound healing and pathological process, the phage-containing hydrogels performed better than the antibiotic alone. The best performance was achieved with the phage-antibiotic hydrogel, indicating a synergistic effect between the phage cocktail and the antibiotic. In conclusion, phage-containing hydrogels eliminate efficiently P. aeruginosa in wounds and may be a proper option for treating infectious wounds.}, }
@article {pmid36991500, year = {2023}, author = {Burckhardt, JC and Chong, DHY and Pett, N and Tropini, C}, title = {Gut commensal Enterocloster species host inoviruses that are secreted in vitro and in vivo.}, journal = {Microbiome}, volume = {11}, number = {1}, pages = {65}, pmid = {36991500}, issn = {2049-2618}, mesh = {Mice ; Animals ; Humans ; *Inovirus/genetics ; *Bacteriophages/genetics ; Bacteria ; Prophages/genetics ; *Gastrointestinal Microbiome ; Clostridiales ; }, abstract = {BACKGROUND: Bacteriophages in the family Inoviridae, or inoviruses, are under-characterized phages previously implicated in bacterial pathogenesis by contributing to biofilm formation, immune evasion, and toxin secretion. Unlike most bacteriophages, inoviruses do not lyse their host cells to release new progeny virions; rather, they encode a secretion system that actively pumps them out of the bacterial cell. To date, no inovirus associated with the human gut microbiome has been isolated or characterized.<br><br>RESULTS: In this study, we utilized in silico, in vitro, and in vivo methods to detect inoviruses in bacterial members of the gut microbiota. By screening a representative genome library of gut commensals, we detected inovirus prophages in Enterocloster spp.&#xa0;(formerly Clostridium spp.). We confirmed the secretion of inovirus particles in in vitro cultures of these organisms using imaging and qPCR. To assess how the gut abiotic environment, bacterial physiology, and inovirus secretion may be linked, we deployed a tripartite in vitro assay that progressively evaluated bacterial&#xa0;growth dynamics, biofilm formation, and inovirus secretion in the presence of changing osmotic environments. Counter to other inovirus-producing bacteria, inovirus production was not correlated with biofilm formation in Enterocloster spp. Instead, the Enterocloster strains had heterogeneous responses to changing osmolality levels relevant to gut physiology. Notably, increasing osmolality induced inovirus secretion in a strain-dependent manner. We confirmed inovirus secretion in a gnotobiotic mouse model inoculated with individual Enterocloster strains in vivo in unperturbed conditions. Furthermore, consistent with our in vitro observations, inovirus secretion was regulated by a changed osmotic environment in the gut due to osmotic laxatives.<br><br>CONCLUSION: In this study, we report on the detection and characterization of novel inoviruses from gut commensals in the Enterocloster genus. Together, our results demonstrate that human gut-associated bacteria can secrete inoviruses and begin to elucidate the environmental niche filled by inoviruses in commensal bacteria. Video Abstract.}, }
@article {pmid36991009, year = {2023}, author = {Liu, X and Zou, L and Nie, C and Qin, Y and Tong, X and Wang, J and Yang, H and Xu, X and Jin, X and Xiao, L and Zhang, T and Min, J and Zeng, Y and Jia, H and Hou, Y}, title = {Mendelian randomization analyses reveal causal relationships between the human microbiome and longevity.}, journal = {Scientific reports}, volume = {13}, number = {1}, pages = {5127}, pmid = {36991009}, issn = {2045-2322}, support = {P01 AG031719/AG/NIA NIH HHS/United States ; }, mesh = {Aged, 80 and over ; Humans ; *Longevity/genetics ; Genome-Wide Association Study ; Mendelian Randomization Analysis ; *Microbiota ; Lactobacillus acidophilus ; }, abstract = {Although recent studies have revealed the association between the human microbiome especially gut microbiota and longevity, their causality remains unclear. Here, we assess the causal relationships between the human microbiome (gut and oral microbiota) and longevity, by leveraging bidirectional two-sample Mendelian randomization (MR) analyses based on genome-wide association studies (GWAS) summary statistics of the gut and oral microbiome from the 4D-SZ cohort and longevity from the CLHLS cohort. We found that some disease-protected gut microbiota such as Coriobacteriaceae and Oxalobacter as well as the probiotic Lactobacillus amylovorus were related to increased odds of longevity, whereas the other gut microbiota such as colorectal cancer pathogen Fusobacterium nucleatum, Coprococcus, Streptococcus, Lactobacillus, and Neisseria were negatively associated with longevity. The reverse MR analysis further revealed genetically longevous individuals tended to have higher abundances of Prevotella and Paraprevotella but lower abundances of Bacteroides and Fusobacterium species. Few overlaps of gut microbiota-longevity interactions were identified across different populations. We also identified abundant links between the oral microbiome and longevity. The additional analysis suggested that centenarians genetically had a lower gut microbial diversity, but no difference in oral microbiota. Our findings strongly implicate these bacteria to play a role in human longevity and underscore the relocation of commensal microbes among different body sites that would need to be monitored for long and healthy life.}, }
@article {pmid36986037, year = {2023}, author = {Cappello, C and Tlais, AZA and Acin-Albiac, M and Lemos Junior, WJF and Pinto, D and Filannino, P and Rinaldi, F and Gobbetti, M and Di Cagno, R}, title = {Identification and Selection of Prospective Probiotics for Enhancing Gastrointestinal Digestion: Application in Pharmaceutical Preparations and Dietary Supplements.}, journal = {Nutrients}, volume = {15}, number = {6}, pages = {}, pmid = {36986037}, issn = {2072-6643}, mesh = {Animals ; Humans ; Prospective Studies ; *Probiotics ; *Lactobacillales ; Digestion ; Pharmaceutical Preparations ; }, abstract = {Our study investigated the effectiveness of 446 strains of lactic acid bacteria (LAB) belonging to different species and isolated from diverse sources (food, human, and animal) as potential probiotic candidates, with the perspective of producing dietary supplements or pharmacological formulations suitable for enhancing gastrointestinal digestion. The survival capability of all the isolates under harsh gastrointestinal tract conditions was evaluated, in which only 44 strains, named high-resistant, were selected for further food digestibility investigations. All 44 strains hydrolyzed raffinose and exhibited amino and iminopeptidase activities but at various extents, confirming species- and strain-specificity. After partial in vitro digestion mimicking oral and gastric digestive phases, food matrices were incubated with single strains for 24 h. Fermented partially digested matrices provided additional functional properties for some investigated strains by releasing peptides and increasing the release of highly bio-accessible free phenolic compounds. A scoring procedure was proposed as an effective tool to reduce data complexity and quantitively characterize the probiotic potential of each LAB strain, which could be more useful in the selection procedure of powerful probiotics.}, }
@article {pmid36984891, year = {2023}, author = {Qin, F and Li, J and Mao, T and Feng, S and Li, J and Lai, M}, title = {2 Hydroxybutyric Acid-Producing Bacteria in Gut Microbiome and Fusobacterium nucleatum Regulates 2 Hydroxybutyric Acid Level In Vivo.}, journal = {Metabolites}, volume = {13}, number = {3}, pages = {}, pmid = {36984891}, issn = {2218-1989}, support = {32170062//National Natural Science Foundation of China/ ; no. 2014//Jiangsu Shuang Chuang team/ ; }, abstract = {2-hydroxybutyric acid (2HB) serves as an important regulatory factor in a variety of diseases. The circulating level of 2HB in serum is significantly higher in multiple diseases, such as cancer and type 2 diabetes (T2D). However, there is currently no systematic study on 2HB-producing bacteria that demonstrates whether gut bacteria contribute to the circulating 2HB pool. To address this question, we used BLASTP to reveal the taxonomic profiling of 2HB-producing bacteria in the human microbiome, which are mainly distributed in the phylum Proteobacteria and Firmicutes. In vitro experiments showed that most gut bacteria (21/32) have at least one path to produce 2HB, which includes Aspartic acid, methionine, threonine, and 2-aminobutyric acid. Particularly, Fusobacterium nucleatum has the strongest ability to synthesize 2HB, which is sufficient to alter colon 2HB concentration in mice. Nevertheless, neither antibiotic (ABX) nor Fusobacterium nucleatum gavage significantly affected mouse serum 2HB levels during the time course of this study. Taken together, our study presents the profiles of 2HB-producing bacteria and demonstrates that gut microbiota was a major contributor to 2HB concentration in the intestinal lumen but a relatively minor contributor to serum 2HB concentration.}, }
@article {pmid36983812, year = {2023}, author = {Wazir, HU and Narang, P and Silvani, G and Mehner, C and Poole, K and Burke, C and Chou, J}, title = {Bacterial Virulence and Prevention for Human Spaceflight.}, journal = {Life (Basel, Switzerland)}, volume = {13}, number = {3}, pages = {}, pmid = {36983812}, issn = {2075-1729}, abstract = {With the advancement in reusable rocket propulsion technology, space tourist trips into outer space are now becoming a possibility at a cost-effective rate. As such, astronauts will face a host of health-related challenges, particularly on long-duration space missions where maintaining a balanced healthy microbiome is going to be vital for human survival in space exploration as well as mission success. The human microbiome involves a whole list of micro-organisms that reside in and on the human host, and plays an integral role in keeping the human host healthy. However, imbalances in the microbiome have been directly linked to many human diseases. Research findings have clearly shown that the outer space environment can directly affect the normal microbiome of astronauts when the astronaut is exposed to the microgravity environment. In this study, we show that the simulation of microgravity on earth can mimic the outer space microgravity environment. Staphylococus aureus (S. aureus) was chosen for this study as it is an opportunistic pathogen, which is part of the normal human skin microflora and the nasal passages. This study's results show that S. aureus proliferation was significantly increased under a microgravity environment compared to Earth's gravity conditions, which complements previous work performed on bacteria in the outer space environment in the International Space Station (ISS). This demonstrates that this technology can be utilised here on Earth to mimic the outer space environment and to study challenging health-related questions. This in return saves us the cost on conducting experiments in the ISS and can help advance knowledge at a faster rate and produce countermeasures to mitigate the negative side effects of the hostile outer space environment on humans.}, }
@article {pmid36983633, year = {2023}, author = {Kartti, S and Bendani, H and Boumajdi, N and Bouricha, EM and Zarrik, O and El Agouri, H and Fokar, M and Aghlallou, Y and El Jaoudi, R and Belyamani, L and Elkhannoussi, B and Ibrahimi, A}, title = {Metagenomics Analysis of Breast Microbiome Highlights the Abundance of Rothia Genus in Tumor Tissues.}, journal = {Journal of personalized medicine}, volume = {13}, number = {3}, pages = {}, pmid = {36983633}, issn = {2075-4426}, abstract = {Breast cancer is one of the main global priorities in terms of public health. It remains the most frequent cancer in women and is the leading cause of their death. The human microbiome plays various roles in maintaining health by ensuring a dynamic balance with the host or in the appearance of various pathologies including breast cancer. In this study, we performed an analysis of bacterial signature differences between tumor and adjacent tissues of breast cancer patients in Morocco. Using 16S rRNA gene sequencing, we observed that adjacent tissue contained a much higher percentage of the Gammaproteobacteria class (35.7%) while tumor tissue was characterized by a higher percentage of Bacilli and Actinobacteria classes, with about 18.8% and 17.2% average abundance, respectively. Analysis of tumor subtype revealed enrichment of genus Sphingomonodas in TNBC while Sphingomonodas was predominant in HER2. The LEfSe and the genus level heatmap analysis revealed a higher abundance of the Rothia genus in tumor tissues. The identified microbial communities can therefore serve as potential biomarkers for prognosis and diagnosis, while also helping to develop new strategies for the treatment of breast cancer patients.}, }
@article {pmid36982257, year = {2023}, author = {Zhao, L and Wang, S and Ilves, M and Lehtonen, S and Saikko, L and El-Nezami, H and Alenius, H and Karisola, P}, title = {Transcriptomic Profiling the Effects of Airway Exposure of Zinc Oxide and Silver Nanoparticles in Mouse Lungs.}, journal = {International journal of molecular sciences}, volume = {24}, number = {6}, pages = {}, pmid = {36982257}, issn = {1422-0067}, support = {307768//Academy of Finland/ ; Personal grant//China Scholarship Council/ ; }, mesh = {Mice ; Animals ; *Zinc Oxide/toxicity ; *Metal Nanoparticles/toxicity ; Silver/toxicity ; Transcriptome ; Lung ; *Nanoparticles ; }, abstract = {Consumers and manufacturers are exposed to nanosized zinc oxide (nZnO) and silver particles (nAg) via airways, but their biological effects are still not fully elucidated. To understand the immune effects, we exposed mice to 2, 10, or 50 μg of nZnO or nAg by oropharyngeal aspiration and analyzed the global gene expression profiles and immunopathological changes in the lungs after 1, 7, or 28 days. Our results show that the kinetics of responses varied in the lungs. Exposure to nZnO resulted in the highest accumulation of F4/80- and CD3-positive cells, and the largest number of differentially expressed genes (DEGs) were identified after day 1, while exposure to nAg caused peak responses at day 7. Additionally, nZnO mainly activated the innate immune responses leading to acute inflammation, whereas the nAg activated both innate and adaptive immune pathways, with long-lasting effects. This kinetic-profiling study provides an important data source to understand the cellular and molecular processes underlying nZnO- and nAg-induced transcriptomic changes, which lead to the characterization of the corresponding biological and toxicological effects of nZnO and nAg in the lungs. These findings could improve science-based hazard and risk assessment and the development of safe applications of engineered nanomaterials (ENMs), e.g., in biomedical applications.}, }
@article {pmid36978455, year = {2023}, author = {Brzozowska, E and Lipiński, T and Korzeniowska-Kowal, A and Filik, K and Górski, A and Gamian, A}, title = {Detection and Level Evaluation of Antibodies Specific to Environmental Bacteriophage I11mO19 and Related Coliphages in Non-Immunized Human Sera.}, journal = {Antibiotics (Basel, Switzerland)}, volume = {12}, number = {3}, pages = {}, pmid = {36978455}, issn = {2079-6382}, abstract = {Bacteriophages (phages) are viruses infecting bacteria. They are widely present in the environment, food, and normal microflora. The human microbiome is a mutually interdependent network of bacteria, bacteriophages, and human cells. The stability of these tri-kingdom interactions may be essential for maintaining immunologic and metabolic health. Phages, as with each other's antigens, may evoke an immune response during a human's lifetime and induce specific antibody generation. In this manuscript, we labeled these antibodies as naturally generated. Naturally generated antibodies may be one of the most important factors limiting the efficacy of phage therapy. Herein, we attempted to determine the physiological level of these antibodies specific to a population bacteriophage named I11mO19 in human sera, using an ELISA-based assay. First, we purified the phage particles and assessed the immunoreactivity of phage proteins. Then, affinity chromatography was performed on columns with immobilized phage proteins to obtain a fraction of human polyclonal anti-phage antibodies. These antibodies were used as a reference to elaborate an immunoenzymatic test that was used to determine the level of natural anti-phage antibodies. We estimated the average level of anti-I11mO19 phage antibodies at 190 µg per one milliliter of human serum. However, immunoblotting revealed that cross-reactivity occurs between some proteins of I11mO19 and two other coliphages: T4 and ΦK1E. The antigens probably share common epitopes, suggesting that the determined level of anti-I11mO19 phage might be overestimated and reflects a group of antibodies reactive to a broad range of other E. coli phages. Anti-I11mO19 antibodies did not react with Pseudomonas bacteriophage F8, confirming specificity to the coliphage group. In this work, we wanted to show whether it is possible to determine the presence and level of anti-phage antibodies in nontargeted-immunized sera, using an immunoenzymatic assay. The conclusion is that it is possible, and specific antibodies can be determined. However, the specificity refers to a broader coliphage group of phages, not only the single phage strain.}, }
@article {pmid36978453, year = {2023}, author = {Dugot, M and Merzon, E and Ashkenazi, S and Vinker, S and Green, I and Golan-Cohen, A and Israel, A}, title = {The Association between Previous Antibiotic Consumption and SARS-CoV-2 Infection: A Population-Based Case-Control Study.}, journal = {Antibiotics (Basel, Switzerland)}, volume = {12}, number = {3}, pages = {}, pmid = {36978453}, issn = {2079-6382}, abstract = {Background: The susceptibility to SARS-CoV-2 infection is complex and not yet fully elucidated, being related to many variables; these include human microbiome and immune status, which are both affected for a long period by antibiotic use. We therefore aimed to examine the association of previous antibiotic consumption and SARS-CoV-2 infection in a large-scale population-based study with control of known confounders. Methods: A matched case-control study was performed utilizing the electronic medical records of a large Health Maintenance Organization. Cases were subjects with confirmed SARS-CoV-2 infection (n = 31,260), matched individually (1:4 ratio) to controls without a positive SARS-CoV-2 test (n = 125,039). The possible association between previous antibiotic use and SARS-CoV-2 infection was determined by comparing antibiotic consumption in the previous 6 and 12 months between the cases and controls. For each antibiotic consumed we calculated the odds ratio (OR) for documented SARS-CoV-2 infection, 95% confidence interval (CI), and p-value using univariate and multivariate analyses. Results: The association between previous antibiotic consumption and SARS-CoV-2 infection was complex and bi-directional. In the multivariate analysis, phenoxymethylpenicillin was associated with increased rate of SARS-CoV-2 infection (OR 1.110, 95% CI: 1.036-1.191) while decreased rates were associated with previous consumption of trimethoprim-sulfonamides (OR 0.783, 95% CI: 0.632-0.971) and azithromycin (OR 0.882, 95% CI: 0.829-0.938). Fluroquinolones were associated with decreased rates (OR 0.923, 95% CI: 0.861-0.989) only in the univariate analysis. Previous consumption of other antibiotics had no significant association with SARS-CoV-2 infection. Conclusions: Previous consumption of certain antibiotic agents has an independent significant association with increased or decreased rates of SARS-CoV-2 infection. Plausible mechanisms, that should be further elucidated, are mainly antibiotic effects on the human microbiome and immune modulation.}, }
@article {pmid36971593, year = {2023}, author = {Liu, F and Lu, H and Dong, B and Huang, X and Cheng, H and Qu, R and Hu, Y and Zhong, L and Guo, Z and You, Y and Xu, ZZ}, title = {Systematic Evaluation of the Viable Microbiome in the Human Oral and Gut Samples with Spike-in Gram+/- Bacteria.}, journal = {mSystems}, volume = {8}, number = {2}, pages = {e0073822}, pmid = {36971593}, issn = {2379-5077}, mesh = {Humans ; *Microbiota/genetics ; DNA ; Feces/microbiology ; DNA, Bacterial/genetics ; Bacteria/genetics ; Firmicutes/genetics ; }, abstract = {PMA (propidium monoazide) is one of the few methods that are compatible with metagenomic sequencing to characterize the live/intact microbiota. However, its efficiency in complex communities such as saliva and feces is still controversial. An effective method for depleting host and dead bacterial DNA in human microbiome samples is lacking. Here, we systematically evaluate the efficiency of osmotic lysis and PMAxx treatment (lyPMAxx) in characterizing the viable microbiome with four live/dead Gram+/Gram- microbial strains in simple synthetic and spiked-in complex communities. We show that lyPMAxx-quantitative PCR (qPCR)/sequencing eliminated more than 95% of the host and heat-killed microbial DNA and had a much smaller effect on the live microbes in both simple mock and spiked-in complex communities. The overall microbial load and the alpha diversity of the salivary and fecal microbiome were decreased by lyPMAxx, and the relative abundances of the microbes were changed. The relative abundances of Actinobacteria, Fusobacteria, and Firmicutes in saliva were decreased by lyPMAxx, as was that of Firmicutes in feces. We also found that the frequently used sample storage method, freezing with glycerol, killed or injured 65% and 94% of the living microbial cells in saliva and feces, respectively, with the Proteobacteria phylum affected most in saliva and the Bacteroidetes and Firmicutes phyla affected most in feces. By comparing the absolute abundance variation of the shared species among different sample types and individuals, we found that sample habitat and personal differences affected the response of microbial species to lyPMAxx and freezing. IMPORTANCE The functions and phenotypes of microbial communities are largely defined by viable microbes. Through advanced nucleic acid sequencing technologies and downstream bioinformatic analyses, we gained an insight into the high-resolution microbial community composition of human saliva and feces, yet we know very little about whether such community DNA sequences represent viable microbes. PMA-qPCR was used to characterize the viable microbes in previous studies. However, its efficiency in complex communities such as saliva and feces is still controversial. By spiking-in four live/dead Gram+/Gram- bacterial strains, we demonstrate that lyPMAxx can effectively discriminate between live and dead microbes in the simple synthetic community and complex human microbial communities (saliva and feces). In addition, freezing storage was found to kill or injure the microbes in saliva and feces significantly, as measured with lyPMAxx-qPCR/sequencing. This method has a promising prospect in the viable/intact microbiota detection of complex human microbial communities.}, }
@article {pmid36971547, year = {2023}, author = {Etienne-Mesmin, L and Meslier, V and Uriot, O and Fournier, E and Deschamps, C and Denis, S and David, A and Jegou, S and Morabito, C and Quinquis, B and Thirion, F and Plaza Oñate, F and Le Chatelier, E and Ehrlich, SD and Blanquet-Diot, S and Almeida, M}, title = {In Vitro Modelling of Oral Microbial Invasion in the Human Colon.}, journal = {Microbiology spectrum}, volume = {11}, number = {2}, pages = {e0434422}, pmid = {36971547}, issn = {2165-0497}, abstract = {Recent advances in the human microbiome characterization have revealed significant oral microbial detection in stools of dysbiotic patients. However, little is known about the potential interactions of these invasive oral microorganisms with commensal intestinal microbiota and the host. In this proof-of-concept study, we proposed a new model of oral-to-gut invasion by the combined use of an in vitro model simulating both the physicochemical and microbial (lumen- and mucus-associated microbes) parameters of the human colon (M-ARCOL), a salivary enrichment protocol, and whole-metagenome shotgun sequencing. Oral invasion of the intestinal microbiota was simulated by injection of enriched saliva in the in vitro colon model inoculated with a fecal sample from the same healthy adult donor. The mucosal compartment of M-ARCOL was able to retain the highest species richness levels over time, while species richness levels decreased in the luminal compartment. This study also showed that oral microorganisms preferably colonized the mucosal microenvironment, suggesting potential oral-to-intestinal mucosal competitions. This new model of oral-to-gut invasion can provide useful mechanistic insights into the role of oral microbiome in various disease processes. IMPORTANCE Here, we propose a new model of oral-to-gut invasion by the combined use of an in vitro model simulating both the physicochemical and microbial (lumen- and mucus-associated microbes) parameters of the human colon (M-ARCOL), a salivary enrichment protocol, and whole-metagenome shotgun sequencing. Our study revealed the importance of integrating the mucus compartment, which retained higher microbial richness during fermentation, showed the preference of oral microbial invaders for the mucosal resources, and indicated potential oral-to-intestinal mucosal competitions. It also underlined promising opportunities to further understand mechanisms of oral invasion into the human gut microbiome, define microbe-microbe and mucus-microbe interactions in a compartmentalized fashion, and help to better characterize the potential of oral microbial invasion and their persistence in the gut.}, }
@article {pmid36969178, year = {2023}, author = {Ling, Z and Cheng, Y and Gao, J and Lei, W and Yan, X and Hu, X and Shao, L and Liu, X and Kang, R}, title = {Alterations of the fecal and vaginal microbiomes in patients with systemic lupus erythematosus and their associations with immunological profiles.}, journal = {Frontiers in immunology}, volume = {14}, number = {}, pages = {1135861}, pmid = {36969178}, issn = {1664-3224}, mesh = {Female ; Humans ; *Gastrointestinal Microbiome/genetics ; Dysbiosis/microbiology ; RNA, Ribosomal, 16S/genetics ; *Microbiota ; Bacteria/genetics ; Feces/microbiology ; *Lupus Erythematosus, Systemic/microbiology ; Vagina/microbiology ; }, abstract = {BACKGROUND: Exploring the human microbiome in multiple body niches is beneficial for clinicians to determine which microbial dysbiosis should be targeted first. We aimed to study whether both the fecal and vaginal microbiomes are disrupted in SLE patients and whether they are correlated, as well as their associations with immunological features.<br><br>METHODS: A group of 30 SLE patients and 30 BMI-age-matched healthy controls were recruited. Fecal and vaginal samples were collected, the 16S rRNA gene was sequenced to profile microbiomes, and immunological features were examined.<br><br>RESULTS: Distinct fecal and vaginal bacterial communities and decreased microbial diversity in feces compared with the vagina were found in SLE patients and controls. Altered bacterial communities were found in the feces and vaginas of patients. Compared with the controls, the SLE group had slightly lower gut bacterial diversity, which was accompanied by significantly higher bacterial diversity in their vaginas. The most predominant bacteria differed between feces and the vagina in all groups. Eleven genera differed in patients' feces; for example, Gardnerella and Lactobacillus increased, whereas Faecalibacterium decreased. Almost all the 13 genera differed in SLE patients' vaginas, showing higher abundances except for Lactobacillus. Three genera in feces and 11 genera in the vagina were biomarkers for SLE patients. The distinct immunological features were only associated with patients' vaginal microbiomes; for example, Escherichia-Shigella was negatively associated with serum C4.<br><br>CONCLUSIONS: Although SLE patients had fecal and vaginal dysbiosis, dysbiosis in the vagina was more obvious than that in feces. Additionally, only the vaginal microbiome interacted with patients' immunological features.}, }
@article {pmid36969036, year = {2023}, author = {Yang, X and An, H and He, Y and Fu, G and Jiang, Z}, title = {Comprehensive analysis of microbiota signature across 32 cancer types.}, journal = {Frontiers in oncology}, volume = {13}, number = {}, pages = {1127225}, pmid = {36969036}, issn = {2234-943X}, abstract = {Microbial communities significantly inhabit the human body. Evidence shows the interaction between the human microbiome and host cells plays a central role in multiple physiological processes and organ microenvironments. However, the majority of related studies focus on gut microbiota or specific tissues/organs, and the component signature of intratumor microbiota across various cancer types remains unclear. Here, we systematically analyzed the correlation between intratumor microbial signature with survival outcomes, genomic features, and immune profiles across 32 cancer types based on the public databases of Bacteria in Cancer (BIC) and The Cancer Genome Atlas (TCGA). Results showed the relative abundance of microbial taxa in tumors compared to normal tissues was observed as particularly noticeable. Survival analysis found that specific candidate microbial taxa were correlated with prognosis across various cancers. Then, a microbial-based scoring system (MS), which was composed of 64 candidate prognostic microbes, was established. Further analyses showed significant differences in survival status, genomic function, and immune profiles among the distinct MS subgroups. Taken together, this study reveals the diversity and complexity of microbiomes in tumors. Classifying cancer into different subtypes based on intratumor microbial signatures might reasonably reflect genomic characteristics, immune features, and survival status.}, }
@article {pmid36966280, year = {2023}, author = {Zhao, Y and Yi, J and Xiang, J and Jia, W and Chen, A and Chen, L and Zheng, L and Zhou, W and Wu, M and Yu, Z and Tang, J}, title = {Exploration of lung mycobiome in the patients with non-small-cell lung cancer.}, journal = {BMC microbiology}, volume = {23}, number = {1}, pages = {81}, pmid = {36966280}, issn = {1471-2180}, mesh = {Humans ; *Mycobiome ; *Carcinoma, Non-Small-Cell Lung ; Fungi/genetics ; *Lung Neoplasms ; Lung ; }, abstract = {As the Human Microbiome Project (HMP) progresses, the relationship between microbes and human health has been receiving increasing attention. A growing number of reports support the correlation between cancer and microbes. However, most studies have focused on bacteria, rather than fungal communities. In this study, we studied the alteration in lung mycobiome in patients with non-small-cell lung cancer (NSCLC) using metagenomic sequencing and qPCR. The higher fungal diversity and more complex network were observed in the patients with NSCLC. In addition, Alternaria arborescens was found as the most relevant fungus to NSCLC, and the enrichment of it in cancerous tissue was also detected. This study proposes that the changes in fungal communities may be closely related to lung cancer, and provides insights into further exploration the relationship between lung cancer and fungi.}, }
@article {pmid36963900, year = {2023}, author = {Elghannam, MT and Hassanien, MH and Ameen, YA and Turky, EA and Elattar, GM and ElRay, AA and Eltalkawy, MD}, title = {Oral microbiota and liver diseases.}, journal = {Clinical nutrition ESPEN}, volume = {54}, number = {}, pages = {68-72}, doi = {10.1016/j.clnesp.2022.12.030}, pmid = {36963900}, issn = {2405-4577}, mesh = {Humans ; *Carcinoma, Hepatocellular ; *Liver Neoplasms ; Dysbiosis ; Liver Cirrhosis ; *Microbiota ; }, abstract = {Gut microbiota plays a crucial role in our health and particularly liver diseases, including NAFLD, cirrhosis, and HCC. Oral microbiome and its role in health and disease represent an active field of research. Several lines of evidence have suggested that oral microbiota dysbiosis represents a major factor contributing to the occurrence and progression of many liver diseases. The human microbiome is valuable to the diagnosis of cancer and provides a novel strategy for targeted therapy of HCC. The most studied liver disease in relation to oral-gut-liver axis dysbiosis includes MAFLD; however, other diseases include Precancerous liver disease as viral liver diseases, liver cirrhosis, AIH and liver carcinoma (HCC). It seems that restoring populations of beneficial organisms and correcting dysbiosis appears to improve outcomes in liver disorders. We discuss the possible role of oral microbiota in these diseases.}, }
@article {pmid36963164, year = {2023}, author = {Beliaeva, MA and Wilmanns, M and Zimmermann, M}, title = {Decipher enzymes from human microbiota for drug discovery and development.}, journal = {Current opinion in structural biology}, volume = {80}, number = {}, pages = {102567}, doi = {10.1016/j.sbi.2023.102567}, pmid = {36963164}, issn = {1879-033X}, mesh = {Humans ; *Gastrointestinal Microbiome ; *Microbiota ; Bacteria/genetics ; Genomics ; Drug Discovery ; }, abstract = {The human microbiota plays an important role in human health and contributes to the metabolism of therapeutic drugs affecting their potency. However, the current knowledge on human gut bacterial metabolism is limited and lacks an understanding of the underlying mechanisms of observed drug biotransformations. Despite the complexity of the gut microbial community, genomic and metagenomic sequencing provides insights into the diversity of chemical reactions that can be carried out by the microbiota and poses new challenges to functionally annotate thousands of bacterial enzymes. Here, we outline methods to systematically address the structural and functional space of the human microbiome, highlighting a combination of in silico and in vitro approaches. Systematic knowledge about microbial enzymes could eventually be applied for personalized therapy, the development of prodrugs and modulators of unwanted bacterial activity, and the further discovery of new antibiotics.}, }
@article {pmid36959568, year = {2023}, author = {Ivashkin, V and Shifrin, O and Maslennikov, R and Poluektova, E and Korolev, A and Kudryavtseva, A and Krasnov, G and Benuni, N and Barbara, G}, title = {Eubiotic effect of rifaximin is associated with decreasing abdominal pain in symptomatic uncomplicated diverticular disease: results from an observational cohort study.}, journal = {BMC gastroenterology}, volume = {23}, number = {1}, pages = {82}, pmid = {36959568}, issn = {1471-230X}, mesh = {Humans ; Rifaximin/therapeutic use ; Cohort Studies ; Prospective Studies ; *Diverticular Diseases/complications/therapy ; Abdominal Pain/drug therapy/etiology ; Treatment Outcome ; }, abstract = {BACKGROUND: Rifaximin effectively treats symptomatic uncomplicated diverticular disease (SUDD) and has shown eubiotic potential (i.e., an increase in resident microbial elements with potential beneficial effects) in other diseases. This study investigated changes in the fecal microbiome of patients with SUDD after repeated monthly treatment with rifaximin and the association of these changes with the severity of abdominal pain.<br><br>METHODS: This was a single-center, prospective, observational, uncontrolled cohort study. Patients received rifaximin 400&#xa0;mg twice a day for 7 days per month for 6 months. Abdominal pain (assessed on a 4-point scale from 0 [no pain] to 3 [severe pain]) and fecal microbiome (assessed using 16&#xa0;S rRNA gene sequencing) were assessed at inclusion (baseline) and 3 and 6 months. The Spearman's rank test analyzed the relationship between changes in the gut microbiome and the severity of abdominal pain. A p-value&#x2009;&#x2264;&#x2009;0.05 was considered statistically significant.<br><br>RESULTS: Of the 23 patients enrolled, 12 patients completed the study and were included in the analysis. Baseline abdominal pain levels decreased significantly after 3 (p&#x2009;=&#x2009;0.036) and 6 (p&#x2009;=&#x2009;0.008) months of treatment with rifaximin. The abundance of Akkermansia in the fecal microbiome was significantly higher at 3 (p&#x2009;=&#x2009;0.017) and 6 (p&#x2009;=&#x2009;0.015) months versus baseline. The abundance of Ruminococcaceae (p&#x2009;=&#x2009;0.034), Veillonellaceae (p&#x2009;=&#x2009;0.028), and Dialister (p&#x2009;=&#x2009;0.036) were significantly increased at 6 months versus baseline, whereas Anaerostipes (p&#x2009;=&#x2009;0.049) was significantly decreased. The severity of abdominal pain was negatively correlated with the abundance of Akkermansia (r=-0.482; p&#x2009;=&#x2009;0.003) and Ruminococcaceae (r=-0.371; p&#x2009;=&#x2009;0.026) but not with Veillonellaceae, Dialister, or Anaerostipes. After 3 months of rifaximin, abdominal pain was significantly less in patients with Akkermansia in their fecal microbiome than in patients without Akkermansia (p&#x2009;=&#x2009;0.022).<br><br>CONCLUSION: The eubiotic effect of rifaximin was associated with decreased abdominal pain in patients with SUDD.}, }
@article {pmid36959210, year = {2023}, author = {Wu, CM and Wheeler, KM and Cárcamo-Oyarce, G and Aoki, K and McShane, A and Datta, SS and Mark Welch, JL and Tiemeyer, M and Griffen, AL and Ribbeck, K}, title = {Mucin glycans drive oral microbial community composition and function.}, journal = {NPJ biofilms and microbiomes}, volume = {9}, number = {1}, pages = {11}, pmid = {36959210}, issn = {2055-5008}, support = {P30 ES002109/ES/NIEHS NIH HHS/United States ; R01 EB017755/EB/NIBIB NIH HHS/United States ; R01-EB017755-041745302/NH/NIH HHS/United States ; }, mesh = {Humans ; *Mucins/chemistry/metabolism ; Glycosylation ; Mucus/metabolism ; *Microbiota ; Polysaccharides/metabolism ; }, abstract = {Human microbiome composition is closely tied to health, but how the host manages its microbial inhabitants remains unclear. One important, but understudied, factor is the natural host environment: mucus, which contains gel-forming glycoproteins (mucins) that display hundreds of glycan structures with potential regulatory function. Leveraging a tractable culture-based system to study how mucins influence oral microbial communities, we found that mucin glycans enable the coexistence of diverse microbes, while resisting disease-associated compositional shifts. Mucins from tissues with unique glycosylation differentially tuned microbial composition, as did isolated mucin glycan libraries, uncovering the importance of specific glycan patterns in microbiome modulation. We found that mucins shape microbial communities in several ways: serving as nutrients to support metabolic diversity, organizing spatial structure through reduced aggregation, and possibly limiting antagonism between competing taxa. Overall, this work identifies mucin glycans as a natural host mechanism and potential therapeutic intervention to maintain healthy microbial communities.}, }
@article {pmid36959041, year = {2023}, author = {Ait-Zenati, F and Djoudi, F and Mehelleb, D and Madaoui, M}, title = {Involvement of the human microbiome in frequent cancers, current knowledge and carcinogenesis mechanisms.}, journal = {Bulletin du cancer}, volume = {110}, number = {7-8}, pages = {776-789}, doi = {10.1016/j.bulcan.2023.01.022}, pmid = {36959041}, issn = {1769-6917}, mesh = {Humans ; *Helicobacter Infections/complications ; *Microbiota ; *Gastrointestinal Microbiome ; Carcinogenesis ; *Liver Neoplasms ; }, abstract = {The human body is home to a complex microbial community, living in symbiosis. However, when an imbalance occurs, known as dysbiosis, it can lead to organic diseases such as cancers. Helicobacter pylori is commonly recognized as the causative agent of gastric cancer. Numerous studies have explored the potential role of other microorganisms in cancers. For example, the role of intestinal microbiota in the hepatocellular carcinoma formation and progression, the microbiota in breast cancer and the interaction between the microbiome and TP53 in human lung carcinogenesis. In this review, we highlight the latest findings on the microbiome involved in the most common cancers and the suggested mechanisms of carcinogenesis.}, }
@article {pmid36957972, year = {2023}, author = {Chen, GY}, title = {The Human Microbiome and Cancer.}, journal = {Cancer journal (Sudbury, Mass.)}, volume = {29}, number = {2}, pages = {47-48}, doi = {10.1097/PPO.0000000000000653}, pmid = {36957972}, issn = {1540-336X}, mesh = {Humans ; *Neoplasms ; *Microbiota ; }, }
@article {pmid36945614, year = {2023}, author = {Gellman, RH and Olm, MR and Terrapon, N and Enam, F and Higginbottom, SK and Sonnenburg, JL and Sonnenburg, ED}, title = {Hadza Prevotella Require Diet-derived Microbiota Accessible Carbohydrates to Persist in Mice.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {36945614}, issn = {2692-8205}, support = {DP1 AT009892/AT/NCCIH NIH HHS/United States ; K22 HG000044/HG/NHGRI NIH HHS/United States ; R01 DK085025/DK/NIDDK NIH HHS/United States ; T32 HG000044/HG/NHGRI NIH HHS/United States ; }, abstract = {Industrialization has transformed the gut microbiota, reducing the prevalence of Prevotella relative to Bacteroides. Here, we isolate Bacteroides and Prevotella strains from the microbiota of Hadza hunter-gatherers of Tanzania, a population with high levels of Prevotella. We demonstrate that plant-derived microbiota-accessible carbohydrates (MACs) are required for persistence of Prevotella copri but not Bacteroides thetaiotaomicron in vivo. Differences in carbohydrate metabolism gene content, expression, and in vitro growth reveal that Hadza Prevotella strains specialize in degrading plant carbohydrates, while Hadza Bacteroides isolates use both plant and host-derived carbohydrates, a difference mirrored in Bacteroides from non-Hadza populations. When competing directly, P. copri requires plant-derived MACs to maintain colonization in the presence of B. thetaiotaomicron, as a no MAC diet eliminates P. copri colonization. Prevotella's reliance on plant-derived MACs and Bacteroides' ability to use host mucus carbohydrates could explain the reduced prevalence of Prevotella in populations consuming a low-MAC, industrialized diet.}, }
@article {pmid36943054, year = {2023}, author = {Zhou, C and Wang, Y and Li, C and Xie, Z and Dai, L}, title = {Amelioration of Colitis by a Gut Bacterial Consortium Producing Anti-Inflammatory Secondary Bile Acids.}, journal = {Microbiology spectrum}, volume = {11}, number = {2}, pages = {e0333022}, pmid = {36943054}, issn = {2165-0497}, abstract = {The Integrative Human Microbiome Project and other cohort studies have indicated that inflammatory bowel disease is accompanied by dysbiosis of gut microbiota, decreased production of secondary bile acids, and increased levels of primary bile acids. Secondary bile acids, such as ursodeoxycholic acid (UDCA) and lithocholic acid (LCA), have been reported to be anti-inflammatory, yet it remains to be studied whether introducing selected bacteria strains to restore bile acid metabolism of the gut microbiome can alleviate intestinal inflammation. In this study, we screened human gut bacterial strains for bile acid metabolism and designed a consortium of three species, including Clostridium AP sp000509125, Bacteroides ovatus, and Eubacterium limosum, and named it BAC (bile acid consortium). We showed that the three-strain gut bacterial consortium BAC is capable of converting conjugated primary bile acids taurochenodeoxycholic acid and glycochenodeoxycholic acid to secondary bile acids UDCA and LCA in vitro. Oral gavage treatment with BAC in mice resulted in protective effects against dextran sulfate sodium (DSS)-induced colitis, including reduced weight loss and increased colon length. Furthermore, BAC treatment increased the fecal level of bile acids, including UDCA and LCA. BAC treatment enhanced intestinal barrier function, which may be attributed to the increased activation of the bile acid receptor TGR5 by secondary bile acids. Finally, we examined the remodeling of gut microbiota by BAC treatment. Taken together, the three-strain gut bacterial consortium BAC restored the dysregulated bile acid metabolism and alleviated DSS-induced colitis. Our study provides a proof-of-concept demonstration that a rationally designed bacterial consortium can reshape the metabolism of the gut microbiome to treat diseases. IMPORTANCE Secondary bile acids have been reported to be anti-inflammatory, yet it remains to be studied whether introducing selected bacteria strains to restore bile acid metabolism of the gut microbiome can alleviate intestinal inflammation. To address this gap, we designed a consortium of human gut bacterial strains based on their metabolic capacity to produce secondary bile acids UDCA and LCA, and we evaluated the efficacy of single bacterial strains and the bacterial consortium in treating the murine colitis model. We found that oral gavage of the bacterial consortium to mice restored secondary bile acid metabolism to increase levels of UDCA and LCA, which induced the activation of TGR5 to improve gut-barrier integrity and reduced the inflammation in murine colitis. Overall, our study demonstrates that rationally designed bacterial consortia can reshape the metabolism of the gut microbiome and provides novel insights into the application of live biotherapeutics for treating IBD.}, }
@article {pmid36930679, year = {2023}, author = {Puschhof, J and Elinav, E}, title = {Human microbiome research: Growing pains and future promises.}, journal = {PLoS biology}, volume = {21}, number = {3}, pages = {e3002053}, pmid = {36930679}, issn = {1545-7885}, mesh = {Humans ; *Microbiota ; Precision Medicine ; }, abstract = {Human microbiome research is evolving from describing associations to understanding the impact of bioactive strains on humans. Despite challenges, progress is being made to apply data-driven microbiome diagnostics and interventions, potentially leading to precision medicine breakthroughs in the next decade.}, }
@article {pmid36929933, year = {2023}, author = {Zou, H and Sun, T and Jin, B and Wang, S}, title = {sBGC-hm: an atlas of secondary metabolite biosynthetic gene clusters from the human gut microbiome.}, journal = {Bioinformatics (Oxford, England)}, volume = {39}, number = {3}, pages = {}, pmid = {36929933}, issn = {1367-4811}, mesh = {Humans ; *Gastrointestinal Microbiome/genetics ; *Microbiota ; Multigene Family ; Biosynthetic Pathways/genetics ; }, abstract = {SUMMARY: Microbial secondary metabolites exhibit potential medicinal value. A large number of secondary metabolite biosynthetic gene clusters (BGCs) in the human gut microbiome, which exhibit essential biological activity in microbe-microbe and microbe-host interactions, have not been adequately characterized, making it difficult to prioritize these BGCs for experimental characterization. Here, we present the sBGC-hm, an atlas of secondary metabolite BGCs allows researchers to explore the potential therapeutic benefits of these natural products. One of its key features is the ability to assist in optimizing the BGC structure by utilizing the gene co-occurrence matrix obtained from Human Microbiome Project data. Results are viewable online and can be downloaded as spreadsheets.<br><br>The database is openly available at https://www.wzubio.com/sbgc. The website is powered by Apache 2 server with PHP and MariaDB.}, }
@article {pmid36920536, year = {2023}, author = {Kazarina, A and Kuzmicka, J and Bortkevica, S and Zayakin, P and Kimsis, J and Igumnova, V and Sadovska, D and Freimane, L and Kivrane, A and Namina, A and Capligina, V and Poksane, A and Ranka, R}, title = {Oral microbiome variations related to ageing: possible implications beyond oral health.}, journal = {Archives of microbiology}, volume = {205}, number = {4}, pages = {116}, pmid = {36920536}, issn = {1432-072X}, mesh = {Humans ; *Oral Health ; *Microbiota ; Bacteria/genetics ; Aging ; Cluster Analysis ; RNA, Ribosomal, 16S ; }, abstract = {The global population is getting older due to a combination of longer life expectancy and declining birth rates. Growing evidence suggests that the oral microbiota composition and distribution may have a profound effect on how well we age. The purpose of this study was to investigate age-related oral microbiome variations of supragingival plaque and buccal mucosa samples in the general population in Latvia. Our results indicated significant difference between supragingival plaque bacterial profiles of three age groups (20-40; 40-60; 60 + years). Within supragingival plaque samples, age group 20-40 showed the highest bacterial diversity with a decline during the 40-60 age period and uprise again after the age of 60. Among other differences, the important oral commensal Neisseria had declined after the age of 40. Additionally, prevalence of two well-documented opportunistic pathogens Streptococcus anginosus and Gemella sanguinis gradually rose with age within our samples. Furthermore, supragingival plaque and buccal mucosa samples significantly differed in overall bacterial composition.}, }
@article {pmid36918089, year = {2023}, author = {Kapoor, B and Gulati, M and Gupta, R and Singla, RK}, title = {Microbiota dysbiosis and myasthenia gravis: Do all roads lead to Rome?.}, journal = {Autoimmunity reviews}, volume = {22}, number = {5}, pages = {103313}, doi = {10.1016/j.autrev.2023.103313}, pmid = {36918089}, issn = {1873-0183}, mesh = {Humans ; Dysbiosis ; Rome ; *Probiotics/therapeutic use ; *Myasthenia Gravis/therapy ; Prebiotics ; *Gastrointestinal Microbiome ; }, abstract = {Dysregulated immune system with a failure to recognize self from non-self-antigens is one of the common pathogeneses seen in autoimmune diseases. The complex interplay of genetic and environmental factors is important for the occurrence and development of the disease. Among the environmental factors, disturbed gut microbiota (gut dysbiosis) has recently attracted particular attention, especially with advancement in human microbiome research. Although the alterations in microbiota have been seen in various autoimmune diseases, including those of nervous system, there is paucity of information on neuromuscular system diseases. Myasthenia gravis (MG) is one such rare autoimmune disease of neuromuscular junction, and is caused by generation of pathogenic autoantibodies to components of the postsynaptic muscle endplate. In the recent years, accumulating evidences have endorsed the key role of host microbiota, particularly those of gut, in the pathogenesis of MG. Differential microbiota composition, characterized by increased abundance of Fusobacteria, Bacteroidetes, and Proteobacteria, and decreased abundance of Actinobacteria and Firmicutes, has been seen in MG patients in comparison to healthy subjects. Disturbance of microbiota composition, particularly reduced ratio of Firmicutes/Bacteroidetes, alter the gut permeability, subsequently triggering the immunological response. Resultant reduction in levels of short chain fatty acids (SCFAs) is another factor contributing to the immunological response in MG patients. Modulation of gut microbiota via intervention of probiotics, prebiotics, synbiotics, postbiotics (metabiotics), and fecal microbiota transplantation (FMT) is considered to be the futuristic approach for the management of MG. This review summarizes the role of gut microbiota and their metabolites (postbiotics) in the progression of MG. Also, various bacteriotherapeutic approaches involving gut microbiota are discussed for the prevention of MG progression.}, }
@article {pmid36916927, year = {2023}, author = {Du, Q and Xu, Q and Pan, F and Shi, Y and Yu, F and Zhang, T and Jiang, J and Liu, W and Pan, X and Han, D and Zhang, H}, title = {Association between Intestinal Colonization and Extraintestinal Infection with Carbapenem-Resistant Klebsiella pneumoniae in Children.}, journal = {Microbiology spectrum}, volume = {11}, number = {2}, pages = {e0408822}, pmid = {36916927}, issn = {2165-0497}, abstract = {Carbapenem-resistant Klebsiella pneumoniae (CRKP) has become a critical public health threat. However, the association between intestinal colonization and parenteral infection among pediatric patients has not been elucidated. We collected 8 fecal CRKP strains and 10 corresponding CRKP strains responsible for extraintestinal infection from eight patients who did not manifest infection upon admission to the hospital. Paired isolates showed identical resistance to antimicrobials and identical virulence in vitro and in vivo. wzi capsule typing, multilocus sequence typing, and whole-genome sequencing (WGS) indicated high similarity between paired colonizing and infecting isolates. Mutations between colonizing and infecting isolate pairs found by WGS had a distinctive molecular signature of a high proportion of complex structural variants. The mutated genes were involved in pathways associated with infection-related physiological and pathogenic functions, including antibiotic resistance, virulence, and response to the extracellular environment. The latter is important for bacterial infection of environmental niches. Various mutations related to antibiotic resistance, virulence, and colonization that were not associated with any particular mutational hot spot correlated with an increased risk of extraintestinal infection. Notably, novel subclone carbapenem-resistant hypervirulent K. pneumoniae (CR-hvKP) KL19-ST15 exhibited hypervirulence in experimental assays that reflected the severe clinical symptoms of two patients infected with the clonal strains. Taken together, our findings indicate the association between CRKP intestinal colonization and extraintestinal infection, suggesting that active screening for colonization on admission could decrease infection risk in children. IMPORTANCE Carbapenem-resistant Klebsiella pneumoniae (CRKP) causes an increasing number of nosocomial infections, which can be life-threatening, as carbapenems are last-resort antibiotics. K. pneumoniae is part of the healthy human microbiome, and this provides a potential advantage for infection. This study demonstrated that CRKP intestinal colonization is strongly linked to extraintestinal infection, based on the evidence given by whole-genome sequencing data and phenotypic assays of antimicrobial resistance and virulence. Apart from these findings, our in-depth analysis of point mutations and chromosome structural variants in patient-specific infecting isolates compared with colonizing isolates may contribute insights into bacterial adaptation underlying CRKP infection. In addition, a novel subclone of carbapenem-resistant hypervirulent K. pneumoniae (CR-hvKP) was observed in the study. This finding highlights the importance of CRKP active surveillance among children, targeting in particular the novel high-risk CR-hvKP clone.}, }
@article {pmid36914394, year = {2022}, author = {Liu, Y and Xu, MM and Zhang, Y and Liu, SQ and Yuan, MQ and Jia, ZJ}, title = {Application Value and Research Progress of Human Microbiome in Sexual Assault Cases.}, journal = {Fa yi xue za zhi}, volume = {38}, number = {6}, pages = {774-782}, doi = {10.12116/j.issn.1004-5619.2021.511101}, pmid = {36914394}, issn = {1004-5619}, mesh = {Child ; Humans ; Female ; Artificial Intelligence ; Forensic Medicine/methods ; *Sex Offenses ; DNA ; *Microbiota ; *Crime Victims ; }, abstract = {In recent years, sexual assault cases have been on the rise, seriously infringing the legitimate rights and interests of women and children, causing widespread concern in society. DNA evidence has become the key evidence to prove the facts in sexual assault cases, but lack of DNA evidence or only DNA evidence in some sexual assault cases leads to unclear facts and insufficient evidence. With the emergence of high-throughput sequencing technology and the development of bioinformatics and artificial intelligence, new progress has been made in the study of human microbiome. Researchers have begun to use human microbiome for difficult sexual assault cases indentification. This paper reviews the characteristics of human microbiome, and its application value in the inferences of the body fluid stain origin, the sexual assault method, the crime time, etc. In addition, the challenges faced by the application of the human microbiome in practical case handling, the solutions and future development potential are analyzed and prospected.}, }
@article {pmid36914054, year = {2023}, author = {Meng, Y and Mao, Y and Tang, Z and Qiu, X and Bajinka, O and Tan, Y and Song, Z}, title = {Crosstalk between the lung microbiome and lung cancer.}, journal = {Microbial pathogenesis}, volume = {178}, number = {}, pages = {106062}, doi = {10.1016/j.micpath.2023.106062}, pmid = {36914054}, issn = {1096-1208}, mesh = {Humans ; Lung/microbiology ; *Lung Neoplasms ; *Pulmonary Disease, Chronic Obstructive ; *Lung Diseases/microbiology ; *Microbiota ; Dysbiosis ; }, abstract = {The human microbiome is a complex ecosystem that mediates interaction between the human host and the environment. All of the human body is colonized by microorganisms. The lung as an organ used to be considered sterile. Recently, however, there has been a growing number of reports with evidence that the lungs are also in a state of carrying bacteria. The pulmonary microbiome is associated with many lung diseases and is increasingly reported in current studies. These include; chronic obstructive pulmonary disease (COPD), asthma, acute chronic respiratory infections, and cancers. These lung diseases are associated with reduced diversity and dysbiosis. It directly or indirectly affects the occurrence and development of lung cancer. Very few microbes directly cause cancer, while many are complicit in cancer growth, usually working through the host's immune system. This review focuses on the correlation between lung microbiota and lung cancer, and investigates the mechanism of action of lung microorganisms on lung cancer, which will provide new and reliable treatments and diagnosis of lung cancer in the future.}, }
@article {pmid36913409, year = {2023}, author = {Mero, S and Lääveri, T and Ursing, J and Rombo, L and Kofoed, PE and Kantele, A}, title = {Seasonal variation of diarrhoeal pathogens among Guinea-Bissauan children under five years of age.}, journal = {PLoS neglected tropical diseases}, volume = {17}, number = {3}, pages = {e0011179}, pmid = {36913409}, issn = {1935-2735}, mesh = {Infant ; Humans ; Child ; Child, Preschool ; Seasons ; Prospective Studies ; Guinea ; *Cryptosporidiosis/complications ; *Cryptosporidium/genetics ; Diarrhea/microbiology ; *Bacteriophages ; }, abstract = {BACKGROUND: Diarrhoea remains a major cause of childhood morbidity and mortality in low-income countries (LICs). The frequency of diarrhoeal episodes may vary by season, yet few prospective cohort studies have examined seasonal variation among various diarrhoeal pathogens using multiplex qPCR to analyse bacterial, viral and parasitic pathogens.<br><br>METHODS: We combined our recent qPCR data of diarrhoeal pathogens (nine bacterial, five viral and four parasitic) among Guinea-Bissauan children under five years old with individual background data, dividing by season. The associations of season (dry winter and rainy summer) and the various pathogens were explored among infants (0-11 months) and young children (12-59 months) and those with and without diarrhoea.<br><br>RESULTS: Many bacterial pathogens, especially EAEC, ETEC and Campylobacter, and parasitic Cryptosporidium, prevailed in the rainy season, whereas many viruses, particularly the adenovirus, astrovirus and rotavirus proved common in the dry season. Noroviruses were found constantly throughout the year. Seasonal variation was observed in both age groups.<br><br>CONCLUSION: In childhood diarrhoea in a West African LIC, seasonal variation appears to favour EAEC, ETEC, and Cryptosporidium in the rainy and viral pathogens in the dry season.}, }
@article {pmid36906264, year = {2023}, author = {Carson, MD and Warner, AJ and Geiser, VL and Hathaway-Schrader, JD and Alekseyenko, AV and Marshall, J and Westwater, C and Novince, CM}, title = {Prolonged Antibiotic Exposure during Adolescence Dysregulates Liver Metabolism and Promotes Adiposity in Mice.}, journal = {The American journal of pathology}, volume = {193}, number = {6}, pages = {796-812}, pmid = {36906264}, issn = {1525-2191}, support = {T32 DE017551/DE/NIDCR NIH HHS/United States ; P30 DK123704/DK/NIDDK NIH HHS/United States ; R01 AG067510/AG/NIA NIH HHS/United States ; K08 DE025337/DE/NIDCR NIH HHS/United States ; P20 GM130457/GM/NIGMS NIH HHS/United States ; R01 LM012517/LM/NLM NIH HHS/United States ; R01 DE029637/DE/NIDCR NIH HHS/United States ; UL1 TR001450/TR/NCATS NIH HHS/United States ; R01 AR081488/AR/NIAMS NIH HHS/United States ; }, mesh = {Male ; Mice ; Animals ; *Adiposity ; *Anti-Bacterial Agents/adverse effects ; Retrospective Studies ; Mice, Inbred C57BL ; Obesity/metabolism ; Liver/metabolism ; Tetracyclines/metabolism ; }, abstract = {Antibiotic administration during early life has been shown to have lasting effects on the gut microbiota, which have been linked to sustained alterations in liver metabolism and adiposity. Recent investigations have discerned that the gut microbiota continues to develop toward an adult-like profile during adolescence. However, the impact of antibiotic exposure during adolescence on metabolism and adiposity is unclear. Herein, a retrospective analysis of Medicaid claims data was performed, which indicated that tetracycline class antibiotics are commonly prescribed for the systemic treatment of adolescent acne. The purpose of this was to discern the impact of a prolonged tetracycline antibiotic exposure during adolescence on the gut microbiota, liver metabolism, and adiposity. Male C57BL/6T specific pathogen-free mice were administered a tetracycline antibiotic during the pubertal/postpubertal adolescent growth phase. Groups were euthanized at different time points to assess immediate and sustained antibiotic treatment effects. Antibiotic exposure during adolescence caused lasting genera-level shifts in the intestinal bacteriome and persistent dysregulation of metabolic pathways in the liver. Dysregulated hepatic metabolism was linked to sustained disruption of the intestinal farnesoid X receptor-fibroblast growth factor 15 axis, a gut-liver endocrine axis that supports metabolic homeostasis. Antibiotic exposure during adolescence increased subcutaneous, visceral, and marrow adiposity, which intriguingly manifested following antibiotic therapy. This preclinical work highlights that prolonged antibiotic courses for the clinical treatment of adolescent acne may have unintended deleterious effects on liver metabolism and adiposity.}, }
@article {pmid36904222, year = {2023}, author = {Rodrigues, A and Gonçalves, A and Morais, J and Araujo, R and Falcão-Pires, I}, title = {Diet-Induced Microbiome's Impact on Heart Failure: A Double-Edged Sword.}, journal = {Nutrients}, volume = {15}, number = {5}, pages = {}, pmid = {36904222}, issn = {2072-6643}, support = {CEECIND/01070/2018//Funda&#xe7;&#xe3;o para a Ci&#xea;ncia e Tecnologia/ ; }, mesh = {Humans ; *Heart Failure ; Quality of Life ; Stroke Volume ; Diet ; *Microbiota ; Inflammation ; Prognosis ; }, abstract = {Heart failure (HF) is a debilitating disease with a significant clinical and economic impact worldwide. Multiple factors seem to increase the risk of developing HF, such as hypertension, obesity and diabetes. Since chronic inflammation plays a significant role in HF pathophysiology and gut dysbiosis is associated with low-grade chronic inflammation, the risk of cardiovascular diseases is likely modulated by the gut microbiome (GM). Considerable progress has been made in HF management. However, there is a need to find new strategies to reduce mortality and increase the quality of life, mainly of HFpEF patients, since its prevalence continues to rise. Recent studies validate that lifestyle changes, such as diet modulation, represent a potential therapeutic approach to improve several cardiometabolic diseases, although their effects on the GM and its indirect cardiac impact still warrant further research. Hence, in this paper, we aim to clarify the link between HF and the human microbiome.}, }
@article {pmid36900377, year = {2023}, author = {Luu, M and Schütz, B and Lauth, M and Visekruna, A}, title = {The Impact of Gut Microbiota-Derived Metabolites on the Tumor Immune Microenvironment.}, journal = {Cancers}, volume = {15}, number = {5}, pages = {}, pmid = {36900377}, issn = {2072-6694}, support = {VI562/7-1//Deutsche Forschungsgemeinschaft/ ; }, abstract = {Prevention of the effectiveness of anti-tumor immune responses is one of the canonical cancer hallmarks. The competition for crucial nutrients within the tumor microenvironment (TME) between cancer cells and immune cells creates a complex interplay characterized by metabolic deprivation. Extensive efforts have recently been made to understand better the dynamic interactions between cancer cells and surrounding immune cells. Paradoxically, both cancer cells and activated T cells are metabolically dependent on glycolysis, even in the presence of oxygen, a metabolic process known as the Warburg effect. The intestinal microbial community delivers various types of small molecules that can potentially augment the functional capabilities of the host immune system. Currently, several studies are trying to explore the complex functional relationship between the metabolites secreted by the human microbiome and anti-tumor immunity. Recently, it has been shown that a diverse array of commensal bacteria synthetizes bioactive molecules that enhance the efficacy of cancer immunotherapy, including immune checkpoint inhibitor (ICI) treatment and adoptive cell therapy with chimeric antigen receptor (CAR) T cells. In this review, we highlight the importance of commensal bacteria, particularly of the gut microbiota-derived metabolites that are capable of shaping metabolic, transcriptional and epigenetic processes within the TME in a therapeutically meaningful way.}, }
@article {pmid36898756, year = {2023}, author = {Farmer, N and Baginski, A and Alkhatib, J and Maki, KA and Baumer, Y and Powell-Wiley, TM and Wallen, GR}, title = {Neighbourhood environment as a risk factor for adverse health outcomes through association with the microbiome: protocol for a scoping review.}, journal = {BMJ open}, volume = {13}, number = {3}, pages = {e066913}, pmid = {36898756}, issn = {2044-6055}, mesh = {Humans ; *Neighborhood Characteristics ; *Outcome Assessment, Health Care ; Research Design ; Risk Factors ; Scoping Reviews As Topic ; }, abstract = {INTRODUCTION: The connection of the microbiome to human health intersects with the physical environment of humans. Each microbiome location can be influenced by environmental conditions that relate to specific geographical locations, which in turn are influenced by social determinants of health such as a neighbourhood. The objective of this scoping review is to explore the current evidence on the relationships between microbiome and neighbourhood to explain microbiome-related health outcomes.<br><br>METHODS AND ANALYSIS: Arksey and O'Malley's literature review framework will be employed throughout the process, as well as Page, et al's 2020 Preferred Reporting Items for Systematic Review and Meta-Analysis updated workflow to process search results. The literature search will be completed using PubMed/Medline (NLM), Embase (Elsevier), Web of Science, Core Collection (Clarivate Analytics), Scopus (Elsevier), medRxiv preprint server and Open Science Framework server. The search will be conducted using a list of pre-identified Medical Subject Headings (MeSH) terms relating to neighbourhood, microbiome and individual characteristics. There will be no date or language restrictions used in the search. In order to be included in the study, a piece must include an evaluation of the relationship between microbiome diversity and neighbourhood (including at least one measurement of the neighbourhood and at least one human microbiome site). Excluded from the review will be those works that do not include all of these measures, literature reviews based on secondary sources and postmortem populations with no report of premortem health factors. The review itself will be an iterative process completed by two reviewers, with a third individual identified to break ties. Documents will be undergoing a risk assessment of bias in order for the authors to comment on the quality of the literature in this area. Finally, results will be discussed with identified stakeholders, including individuals connected to neighbourhoods facing structural inequity and experts in the topics of study through a community advisory board, for their feedback and knowledge transfer.<br><br>ETHICS AND DISSEMINATION: This review does not require ethical approval. Results of this search will be disseminated through peer-reviewed publications. Furthermore, this work is completed in conjunction with a community advisory board so as to ensure dissemination to multiple stakeholders.}, }
@article {pmid36896938, year = {2023}, author = {Fekete, EE and Figeys, D and Zhang, X}, title = {Microbiota-directed biotherapeutics: considerations for quality and functional assessment.}, journal = {Gut microbes}, volume = {15}, number = {1}, pages = {2186671}, pmid = {36896938}, issn = {1949-0984}, mesh = {Humans ; *Gastrointestinal Microbiome ; *Microbiota ; *Neoplasms ; *Gastrointestinal Diseases ; *Metabolic Diseases ; }, abstract = {Mounting evidence points to causative or correlative roles of gut microbiome in the development of a myriad of diseases ranging from gastrointestinal diseases, metabolic diseases to neurological disorders and cancers. Consequently, efforts have been made to develop and apply therapeutics targeting the human microbiome, in particular the gut microbiota, for treating diseases and maintaining wellness. Here we summarize the current development of gut microbiota-directed therapeutics with a focus on novel biotherapeutics, elaborate the need of advanced -omics approaches for evaluating the microbiota-type biotherapeutics, and discuss the clinical and regulatory challenges. We also discuss the development and potential application of ex vivo microbiome assays and in vitro intestinal cellular models in this context. Altogether, this review aims to provide a broad view of promises and challenges of the emerging field of microbiome-directed human healthcare.}, }
@article {pmid36891192, year = {2023}, author = {Jeong, J and Ahn, K and Mun, S and Yun, K and Kim, YT and Jung, W and Lee, KE and Kim, MY and Ahn, Y and Han, K}, title = {Understanding the bacterial compositional network associations between oral and gut microbiome within healthy Koreans.}, journal = {Journal of oral microbiology}, volume = {15}, number = {1}, pages = {2186591}, pmid = {36891192}, issn = {2000-2297}, abstract = {Oral microbial ecosystem could influence intestinal diseases, but there have been insufficient studies demonstrating the association of microbial composition between the oral cavity and the intestinal system. Thus, we aimed to investigate the compositional network within the oral microbiome related to gut enterotype from saliva and stool samples collected from 112 healthy Korean subjects. Here, we performed bacterial 16S amplicon sequencing from clinical samples. Then, we determined oral microbiome type related to individual's gut enterotype for healthy Korean. The co-occurrence analysis was performed to interactivity prediction of microbiome within saliva samples. As a result, it could be classified into two Korean oral microbiome types (KO) and four oral-gut-associated microbiome types (KOGA) according to distribution and significant differences of oral microflora. The co-occurrence analysis showed various bacterial compositional networks linked around Streptococcus and Haemophilus within healthy subjects. The present study was first approach in healthy Koreans to identify the oral microbiome types related to the gut microbiome and investigate their characteristics. Hence, we suggest that our results could be potential healthy control data for identifying differences in microbial composition between healthy people and oral disease patients and studying microbial association with the gut microbial environment (oral-gut microbiome axis).}, }
@article {pmid36890166, year = {2023}, author = {Pasinetti, GM and Turroni, S and Palmieri, J and De Filippo, C}, title = {Human microbiome collection.}, journal = {Scientific reports}, volume = {13}, number = {1}, pages = {3807}, pmid = {36890166}, issn = {2045-2322}, mesh = {Humans ; *Microbiota ; *Gastrointestinal Microbiome ; RNA, Ribosomal, 16S ; }, }
@article {pmid36889023, year = {2023}, author = {Shanahan, F and Ghosh, TS and O'Toole, PW}, title = {Human microbiome variance is underestimated.}, journal = {Current opinion in microbiology}, volume = {73}, number = {}, pages = {102288}, doi = {10.1016/j.mib.2023.102288}, pmid = {36889023}, issn = {1879-0364}, mesh = {Humans ; *Microbiota ; Life Style ; Aging ; }, abstract = {Most of the variance in the human microbiome remains unexplained. Although an extensive list of individual lifestyles shaping the microbiome has been identified, important gaps in knowledge persist. Most human microbiome data are from individuals living in socioeconomically developed countries. This may have skewed the interpretation of microbiome variance and its relationship to health and disease. Moreover, striking under-representation of minority groups in microbiome studies is a missed opportunity to assess context, history and the changing nature of the microbiome in relation to the risk of disease. Therefore, we focus here on areas of recent progress - ageing and ethnicity - both of which contribute to microbiome variance with particular lessons for the promise of microbiome-based diagnostics and therapeutics.}, }
@article {pmid36871794, year = {2023}, author = {Moran, GP and Zgaga, L and Daly, B and Harding, M and Montgomery, T}, title = {Does fluoride exposure impact on the human microbiome?.}, journal = {Toxicology letters}, volume = {379}, number = {}, pages = {11-19}, doi = {10.1016/j.toxlet.2023.03.001}, pmid = {36871794}, issn = {1879-3169}, mesh = {Animals ; Humans ; Fluorides/toxicity ; Fluoridation/adverse effects ; Food ; *Microbiota ; *Fluorosis, Dental ; }, abstract = {Fluoride is added to drinking water in some countries to prevent tooth decay (caries). There is no conclusive evidence that community water fluoridation (CWF) at WHO recommended concentrations for caries prevention has any harmful effects. However, research is ongoing regarding potential effects of ingested fluoride on human neurodevelopment and endocrine dysfunction. Simultaneously, research has emerged highlighting the significance of the human microbiome in gastrointestinal and immune health. In this review we evaluate the literature examining the effect of fluoride exposure on the human microbiome. Unfortunately, none of the studies retrieved examined the effects of ingested fluoridated water on the human microbiome. Animal studies generally examined acute fluoride toxicity following ingestion of fluoridated food and water and conclude that fluoride exposure can detrimentally perturb the normal microbiome. These data are difficult to extrapolate to physiologically relevant human exposure dose ranges and the significance to humans living in areas with CWF requires further investigation. Conversely, evidence suggests that the use of fluoride containing oral hygiene products may have beneficial effects on the oral microbiome regarding caries prevention. Overall, while fluoride exposure does appear to impact the human and animal microbiome, the long-term consequences of this requires further study.}, }
@article {pmid36869345, year = {2023}, author = {Li, J and Jing, Q and Li, J and Hua, M and Di, L and Song, C and Huang, Y and Wang, J and Chen, C and Wu, AR}, title = {Assessment of microbiota in the gut and upper respiratory tract associated with SARS-CoV-2 infection.}, journal = {Microbiome}, volume = {11}, number = {1}, pages = {38}, pmid = {36869345}, issn = {2049-2618}, mesh = {Humans ; *COVID-19 ; SARS-CoV-2 ; *Microbiota ; *Gastrointestinal Microbiome ; Nose ; }, abstract = {BACKGROUND: The human microbiome plays an important role in modulating the host metabolism and immune system. Connections and interactions have been found between the microbiome of the gut and oral pharynx in the context of SARS-CoV-2 and other viral infections; hence, to broaden our understanding of host-viral responses in general and to deepen our knowledge of COVID-19, we performed a large-scale, systematic evaluation of the effect of SARS-CoV-2 infection on human microbiota in patients with varying disease severity.<br><br>RESULTS: We processed 521 samples from 203 COVID-19 patients with varying disease severity and 94 samples from 31 healthy donors, consisting of 213 pharyngeal swabs, 250 sputa, and 152 fecal samples, and obtained meta-transcriptomes as well as SARS-CoV-2 sequences from each sample. Detailed assessment of these samples revealed altered microbial composition and function in the upper respiratory tract (URT) and gut of COVID-19 patients, and these changes are significantly associated with disease severity. Moreover, URT and gut microbiota show different patterns of alteration, where gut microbiome seems to be more variable and in direct correlation with viral load; and microbial community in the upper respiratory tract renders a high risk of antibiotic resistance. Longitudinally, the microbial composition remains relatively stable during the study period.<br><br>CONCLUSIONS: Our study has revealed different trends and the relative sensitivity of microbiome in different body sites to SARS-CoV-2 infection. Furthermore, while the use of antibiotics is often essential for the prevention and treatment of secondary infections, our results indicate a need to evaluate potential antibiotic resistance in the management of COVID-19 patients in the ongoing pandemic. Moreover, a longitudinal follow-up to monitor the restoration of the microbiome could enhance our understanding of the long-term effects of COVID-19. Video Abstract.}, }
@article {pmid36868921, year = {2023}, author = {Bukavina, L and Isali, I and Ginwala, R and Sindhani, M and Calaway, A and Magee, D and Miron, B and Correa, A and Kutikov, A and Zibelman, M and Ghannoum, M and Retuerto, M and Ponsky, L and Markt, S and Uzzo, R and Abbosh, P}, title = {Global Meta-analysis of Urine Microbiome: Colonization of Polycyclic Aromatic Hydrocarbon-degrading Bacteria Among Bladder Cancer Patients.}, journal = {European urology oncology}, volume = {6}, number = {2}, pages = {190-203}, doi = {10.1016/j.euo.2023.02.004}, pmid = {36868921}, issn = {2588-9311}, support = {P30 CA043703/CA/NCI NIH HHS/United States ; P30 CA006927/CA/NCI NIH HHS/United States ; R01 AI145289/AI/NIAID NIH HHS/United States ; }, mesh = {Adult ; Humans ; Bacteria/genetics ; *Urinary Bladder Neoplasms/urine ; *Microbiota/genetics ; Motivation ; RNA, Ribosomal, 16S/genetics ; }, abstract = {BACKGROUND: The application of next-generation sequencing techniques has enabled characterization of urinary tract microbiome. Although many studies have demonstrated associations between the human microbiome and bladder cancer (BC), these have not always reported consistent results, thereby necessitating cross-study comparisons. Thus, the fundamental questions remain how we can utilize this knowledge.<br><br>OBJECTIVE: The aim of our study was to examine the disease-associated changes in urine microbiome communities globally utilizing a machine learning algorithm.<br><br>Raw FASTQ files were downloaded for the three published studies in urinary microbiome in BC patients, in addition to our own prospectively collected cohort.<br><br>Demultiplexing and classification were performed using the QIIME 2020.8 platform. De novo operational taxonomic units were clustered using the uCLUST algorithm and defined by 97% sequence similarity and classified at the phylum level against the Silva RNA sequence database. The metadata available from the three studies included were used to evaluate the differential abundance between BC patients and controls via a random-effect meta-analysis using the metagen R function. A machine learning analysis was performed using the SIAMCAT R package.<br><br>RESULTS AND LIMITATIONS: Our study includes 129 BC urine and 60 healthy control samples across four different countries. We identified a total of 97/548 genera to be differentially abundant in the BC urine microbiome compared with that of healthy patients. Overall, while the differences in diversity metrics were clustered around the country of origin (Kruskal-Wallis, p&#xa0;<&#xa0;0.001), collection methodology was a driver of microbiome composition. When assessing dataset from China, Hungary, and Croatia, data demonstrated no discrimination capacity to distinguish between BC patients and healthy adults (area under the curve [AUC] 0.577). However, inclusion of samples with catheterized urine improved the diagnostic accuracy of prediction for BC to AUC 0.995, with precision-recall AUC&#xa0;=&#xa0;0.994. Through elimination of contaminants associated with the collection methodology among all cohorts, our study identified increased abundance of polycyclic aromatic hydrocarbon (PAH)-degrading bacteria Sphingomonas, Acinetobacter, Micrococcus, Pseudomonas, and Ralstonia to be consistently present in BC patients.<br><br>CONCLUSIONS: The microbiota of the BC population may be a reflection of PAH exposure from smoking, environmental pollutants, and ingestion. Presence of PAHs in the urine of BC patients may allow for a unique metabolic niche and provide necessary metabolic resources where other bacteria are not able to flourish. Furthermore, we found that while compositional differences are associated with geography more than with disease, many are driven by the collection methodology.<br><br>PATIENT SUMMARY: The goal of our study was to compare the urine microbiome of bladder cancer patients with that of healthy controls and evaluate any potential bacteria that may be more likely to be found in patients with bladder cancer. Our study is unique as it evaluates this across multiple countries, to find a common pattern. After we removed some of the contamination, we were able to localize several key bacteria that are more likely to be found in the urine of bladder cancer patients. These bacteria all share their ability to break down tobacco carcinogens.}, }
@article {pmid36862015, year = {2023}, author = {Meslé, MM and Gray, CR and Dlakić, M and DuBois, JL}, title = {Bacteroides thetaiotaomicron, a Model Gastrointestinal Tract Species, Prefers Heme as an Iron Source, Yields Protoporphyrin IX as a Product, and Acts as a Heme Reservoir.}, journal = {Microbiology spectrum}, volume = {11}, number = {2}, pages = {e0481522}, pmid = {36862015}, issn = {2165-0497}, support = {P20 GM103474/GM/NIGMS NIH HHS/United States ; R35 GM136390/GM/NIGMS NIH HHS/United States ; }, abstract = {Members of the phylum Bacteroidetes are abundant in healthy gastrointestinal (GI) tract flora. Bacteroides thetaiotaomicron is a commensal heme auxotroph and representative of this group. Bacteroidetes are sensitive to host dietary iron restriction but proliferate in heme-rich environments that are also associated with colon cancer. We hypothesized that B. thetaiotaomicron may act as a host reservoir for iron and/or heme. In this study, we defined growth-promoting quantities of iron for B. thetaiotaomicron. B. thetaiotaomicron preferentially consumed and hyperaccumulated iron in the form of heme when presented both heme and nonheme iron sources in excess of its growth needs, leading to an estimated 3.6 to 8.4 mg iron in a model GI tract microbiome consisting solely of B. thetaiotaomicron. Protoporphyrin IX was identified as an organic coproduct of heme metabolism, consistent with anaerobic removal of iron from the heme leaving the intact tetrapyrrole as the observed product. Notably, no predicted or discernible pathway for protoporphyrin IX generation exists in B. thetaiotaomicron. Heme metabolism in congeners of B. thetaiotaomicron has previously been associated with the 6-gene hmu operon, based on genetic studies. A bioinformatics survey demonstrated that the intact operon is widespread in but confined to members of the Bacteroidetes phylum and ubiquitous in healthy human GI tract flora. Anaerobic heme metabolism by commensal Bacteroidetes via hmu is likely a major contributor to human host metabolism of the heme from dietary red meat and a driver for the selective growth of these species in the GI tract consortium. IMPORTANCE Research on bacterial iron metabolism has historically focused on the host-pathogen relationship, where the host suppresses pathogen growth by cutting off access to iron. Less is known about how host iron is shared with bacterial species that live commensally in the anaerobic human GI tract, typified by members of phylum Bacteroidetes. While many facultative pathogens avidly produce and consume heme iron, most GI tract anaerobes are heme auxotrophs whose metabolic preferences we aimed to describe. Understanding iron metabolism by model microbiome species like Bacteroides thetaiotaomicron is essential for modeling the ecology of the GI tract, which serves the long-term biomedical goals of manipulating the microbiome to facilitate host metabolism of iron and remediate dysbiosis and associated pathologies (e.g., inflammation and cancer).}, }
@article {pmid36861799, year = {2023}, author = {Plotnikov, E and Pukhnyarskaya, D and Chernova, A}, title = {Lithium and Microorganisms: Biological Effects and Mechanisms.}, journal = {Current pharmaceutical biotechnology}, volume = {24}, number = {13}, pages = {1623-1629}, doi = {10.2174/1389201024666230302153849}, pmid = {36861799}, issn = {1873-4316}, mesh = {Humans ; *Lithium/pharmacology ; *Microbiota/drug effects ; Soil Microbiology ; Gastrointestinal Microbiome/drug effects ; }, abstract = {This review covers the lithium effects on microorganisms, including gut and soil bacteria. Available studies of the biological effects of lithium salts have revealed a wide range of different effects of lithium cations on various microorganisms, but so far, the study of this direction has not been summarized enough. Here we consider the confirmed and various plausible mechanisms of lithium action on microorganisms. Special emphasis is placed on assessing the effect of lithium ions under oxidative stress and adverse environmental conditions. The impact of lithium on the human microbiome is also being reviewed and discussed. Controversial effects of lithium have been shown, including the inhibitory and stimulating effects of lithium on bacterial growth.}, }
@article {pmid36841913, year = {2023}, author = {Stockdale, SR and Shkoporov, AN and Khokhlova, EV and Daly, KM and McDonnell, SA and O' Regan, O and Nolan, JA and Sutton, TDS and Clooney, AG and Ryan, FJ and Sheehan, D and Lavelle, A and Draper, LA and Shanahan, F and Ross, RP and Hill, C}, title = {Interpersonal variability of the human gut virome confounds disease signal detection in IBD.}, journal = {Communications biology}, volume = {6}, number = {1}, pages = {221}, pmid = {36841913}, issn = {2399-3642}, support = {SFI/12/RC/2273//Science Foundation Ireland (SFI)/ ; 101001684//EC | EU Framework Programme for Research and Innovation H2020 | H2020 Priority Excellent Science | H2020 European Research Council (H2020 Excellent Science - European Research Council)/ ; SFI/14/SP APC/B3032//Science Foundation Ireland (SFI)/ ; 220646/Z/20/Z//Wellcome Trust (Wellcome)/ ; /WT_/Wellcome Trust/United Kingdom ; }, mesh = {Humans ; Virome/genetics ; *Gastrointestinal Microbiome/genetics ; *Viruses/genetics ; *Colitis, Ulcerative/genetics/microbiology ; *Inflammatory Bowel Diseases/genetics ; }, abstract = {Viruses are increasingly recognised as important components of the human microbiome, fulfilling numerous ecological roles including bacterial predation, immune stimulation, genetic diversification, horizontal gene transfer, microbial interactions, and augmentation of metabolic functions. However, our current view of the human gut virome is tainted by previous sequencing requirements that necessitated the amplification of starting nucleic acids. In this study, we performed an original longitudinal analysis of 40 healthy control, 19 Crohn's disease, and 20 ulcerative colitis viromes over three time points without an amplification bias, which revealed and highlighted the interpersonal individuality of the human gut virome. In contrast to a 16 S rRNA gene analysis of matched samples, we show that α- and β-diversity metrics of unamplified viromes are not as efficient at discerning controls from patients with inflammatory bowel disease. Additionally, we explored the intrinsic properties of unamplified gut viromes and show there is considerable interpersonal variability in viral taxa, infrequent longitudinal persistence of intrapersonal viruses, and vast fluctuations in the abundance of temporal viruses. Together, these properties of unamplified faecal viromes confound the ability to discern disease associations but significantly advance toward an unbiased and accurate representation of the human gut virome.}, }
@article {pmid36841736, year = {2023}, author = {Wang, Q and Liu, Z and Ma, A and Li, Z and Liu, B and Ma, Q}, title = {Computational methods and challenges in analyzing intratumoral microbiome data.}, journal = {Trends in microbiology}, volume = {31}, number = {7}, pages = {707-722}, pmid = {36841736}, issn = {1878-4380}, support = {R01 GM131399/GM/NIGMS NIH HHS/United States ; }, mesh = {Humans ; *Microbiota ; *Neoplasms/therapy ; Immunotherapy/methods ; Computational Biology/methods ; Forecasting ; }, abstract = {The human microbiome is intimately related to cancer biology and plays a vital role in the efficacy of cancer treatments, including immunotherapy. Extraordinary evidence has revealed that several microbes influence tumor development through interaction with the host immune system, that is, immuno-oncology-microbiome (IOM). This review focuses on the intratumoral microbiome in IOM and describes the available data and computational methods for discovering biological insights of microbial profiling from host bulk, single-cell, and spatial sequencing data. Critical challenges in data analysis and integration are discussed. Specifically, the microorganisms associated with cancer and cancer treatment in the context of IOM are collected and integrated from the literature. Lastly, we provide our perspectives for future directions in IOM research.}, }
@article {pmid36841691, year = {2023}, author = {Wright, JT}, title = {The human microbiome: The mouth and beyond.}, journal = {Journal of the American Dental Association (1939)}, volume = {154}, number = {4}, pages = {277-278}, doi = {10.1016/j.adaj.2023.02.007}, pmid = {36841691}, issn = {1943-4723}, mesh = {Humans ; *Mouth ; *Microbiota ; Face ; }, }
@article {pmid36840551, year = {2023}, author = {Tierney, BT and Van den Abbeele, P and Al-Ghalith, GA and Verstrepen, L and Ghyselinck, J and Calatayud, M and Marzorati, M and Gadir, AA and Daisley, B and Reid, G and Bron, PA and Gevers, D and Dhir, R and Simmons, SL}, title = {Capacity of a Microbial Synbiotic To Rescue the In Vitro Metabolic Activity of the Gut Microbiome following Perturbation with Alcohol or Antibiotics.}, journal = {Applied and environmental microbiology}, volume = {89}, number = {3}, pages = {e0188022}, pmid = {36840551}, issn = {1098-5336}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Synbiotics ; Anti-Bacterial Agents/pharmacology ; Ethanol ; Fatty Acids, Volatile/metabolism ; Butyrates ; }, abstract = {The human gut microbiome contributes crucial bioactive metabolites that support human health and is sensitive to perturbations from the ingestion of alcohol and antibiotics. We interrogated the response and recovery of human gut microbes after acute alcohol or broad-spectrum antibiotic administration in a gut model simulating the luminal and mucosal colonic environment with an inoculated human microbiome. Both alcohol and antibiotic treatments reduced the production of major short-chain fatty acids (SCFAs) (acetate, propionate, and butyrate), which are established modulators of human health. Treatment with a microbial synbiotic restored and enhanced gut function. Butyrate and acetate production increased by up to 29.7% and 18.6%, respectively, relative to untreated, dysbiotic samples. In parallel, treatment led to increases in the relative abundances of beneficial commensal organisms not found in the synbiotic (e.g., Faecalibacterium prausnitzii and the urolithin-producing organism Gordonibacter pamelaeae) as well as species present in the synbiotic (e.g., Bifidobacterium infantis), suggesting synergistic interactions between supplemented and native microorganisms. These results lead us to conclude that functional shifts in the microbiome, evaluated by both metabolite production and specific taxonomic compositional changes, are an appropriate metric to assess microbiome "recovery" following a dysbiosis-inducing disruption. Overall, these findings support the execution of randomized clinical studies to determine whether a microbial synbiotic can help restore microbiome function after a disruption. IMPORTANCE The human gut microbiome is sensitive to disruptions by common stressors such as alcohol consumption and antibiotic treatment. In this study, we used an in vitro system modeling the gut microbiome to investigate whether treatment with a microbial synbiotic can help restore microbiome function after stress. We find that a complex gut community treated with alcohol or antibiotics showed reduced levels of production of short-chain fatty acids, which are critical beneficial molecules produced by a healthy gut microbiota. Treatment of stressed communities with a microbial synbiotic resulted in the recovery of SCFA production as well as an increase in the abundance of beneficial commensal organisms. Our results suggest that treatment with a microbial synbiotic has the potential to restore healthy gut microbiome function after stress and merits further investigation in clinical studies.}, }
@article {pmid36838304, year = {2023}, author = {Moraes, MM and Mendes, TT and Borges, L and Marques, AL and Núñez-Espinosa, C and Gonçalves, DAP and Simões, CB and Vieira, TS and Ladeira, RVP and Lourenço, TGB and Ribeiro, DV and Hatanaka, E and Heller, D and Arantes, RME}, title = {A 7-Week Summer Camp in Antarctica Induces Fluctuations on Human Oral Microbiome, Pro-Inflammatory Markers and Metabolic Hormones Profile.}, journal = {Microorganisms}, volume = {11}, number = {2}, pages = {}, pmid = {36838304}, issn = {2076-2607}, support = {442645/2018-0//CNPq/MCTIC/CAPES/FNDCT/PROANTAR/ ; AEC-00017-18; CDS- PPM 000304/16; CBB- APQ-01419-14; DAPG- APQ-01268-21//Funda&#xe7;&#xe3;o de Amparo &#xe0; Pesquisa do Estado de Minas Gerais (FAPEMIG)/ ; PRPq-UFMG//Pr&#xf3;-Reitoria de Pesquisa da Universidade Federal de Minas Gerais/ ; 311976/2021-2//Conselho Nacional de Desenvolvimento Cient&#xed;fico e Tecnol&#xf3;gico (CNPq)/ ; 88887.321687/2019-00 88882.314890/2013-01//Coordena&#xe7;&#xe3;o de Aperfei&#xe7;oamento de Pessoal de N&#xed;vel Superior - Brasil (CAPES) - Finance Code 001/ ; }, abstract = {Antarctic camps pose psychophysiological challenges related to isolated, confined, and extreme (ICE) conditions, including meals composed of sealed food. ICE conditions can influence the microbiome and inflammatory responses. Seven expeditioners took part in a 7-week Antarctic summer camp (Nelson Island) and were evaluated at Pre-Camp (i.e., at the beginning of the ship travel), Camp-Initial (i.e., 4th and 5th day in camp), Camp-Middle (i.e., 19th-20th, and 33rd-34th days), Camp-Final (i.e., 45th-46th day), and at the Post-Camp (on the ship). At the Pre-Camp, Camp-Initial, and Camp-Final, we assessed microbiome and inflammatory markers. Catecholamines were accessed Pre- and Post-Camp. Heart rate variability (HRV), leptin, thyroid stimulating hormone (TSH), and thyroxine (T4) were accessed at all time points. Students' t-tests or repeated-measures analysis of variance (one or two-way ANOVA) followed by Student-Newman-Keuls (post hoc) were used for parametric analysis. Kruskal-Wallis test was applied for non-parametric analysis. Microbiome analysis showed a predominance of Pseudomonadota (34.01%), Bacillota (29.82%), and Bacteroidota (18.54%), followed by Actinomycetota (5.85%), and Fusobacteria (5.74%). Staying in a long-term Antarctic camp resulted in microbiome fluctuations with a reduction in Pseudomonadota-a "microbial signature" of disease. However, the pro-inflammatory marker leptin and IL-8 tended to increase, and the angiogenic factor VEGF was reduced during camp. These results suggest that distinct Antarctic natural environments and behavioral factors modulate oral microbiome and inflammation.}, }
@article {pmid36838283, year = {2023}, author = {Morrison, AG and Sarkar, S and Umar, S and Lee, STM and Thomas, SM}, title = {The Contribution of the Human Oral Microbiome to Oral Disease: A Review.}, journal = {Microorganisms}, volume = {11}, number = {2}, pages = {}, pmid = {36838283}, issn = {2076-2607}, support = {P30 CA168524/CA/NCI NIH HHS/United States ; }, abstract = {The oral microbiome is an emerging field that has been a topic of discussion since the development of next generation sequencing and the implementation of the human microbiome project. This article reviews the current literature surrounding the oral microbiome, briefly highlighting most recent methods of microbiome characterization including cutting edge omics, databases for the microbiome, and areas with current gaps in knowledge. This article also describes reports on microorganisms contained in the oral microbiome which include viruses, archaea, fungi, and bacteria, and provides an in-depth analysis of their significant roles in tissue homeostasis. Finally, we detail key bacteria involved in oral disease, including oral cancer, and the current research surrounding their role in stimulation of inflammatory cytokines, the role of gingival crevicular fluid in periodontal disease, the creation of a network of interactions between microorganisms, the influence of the planktonic microbiome and cospecies biofilms, and the implications of antibiotic resistance. This paper provides a comprehensive literature analysis while also identifying gaps in knowledge to enable future studies to be conducted.}, }
@article {pmid36837548, year = {2023}, author = {Iavarone, I and Greco, PF and La Verde, M and Morlando, M and Torella, M and de Franciscis, P and Ronsini, C}, title = {Correlations between Gut Microbial Composition, Pathophysiological and Surgical Aspects in Endometriosis: A Review of the Literature.}, journal = {Medicina (Kaunas, Lithuania)}, volume = {59}, number = {2}, pages = {}, pmid = {36837548}, issn = {1648-9144}, mesh = {Female ; Humans ; *Endometriosis/pathology ; *Gastrointestinal Microbiome/physiology ; *Microbiota ; Uterus ; *Probiotics ; }, abstract = {Background and Objectives: Endometriosis is an estrogen-dependent, inflammatory, gynecological disorder represented by the migration of endometrial tissue outside the uterus. It can manifest through gynecological and gastrointestinal (GI) signs. Given the hormonal imbalances in endometriosis and the effect of microbiota on immune dysfunction, it has been thought that the human microbiome may play a role in its pathogenesis, acting differently before and after laparotomy. The aim of this review is to establish whether there is an interaction between endometriosis and gut microbial composition. Materials and Methods: We aimed to review available literature by systematically searching five databases: PubMed, EMBASE, Scopus, Cochrane Library, and ScienceDirect. We included records describing gut microbiota in the context of endometriosis-observing PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) guidelines-to recognize the presence of disease by the expression of bacterial taxa-based on 16S ribosomal RNA gene sequencing analysis. Results: Among 10 studies selected, there were four review articles and six clinical trials. The latter identified significant differences at a genus level in increased Prevotella, Blautia, and Bifidobacterium and decreased Paraprevotella, Ruminococcus, and Lachnospira (p < 0.05). In patients undergoing abdominal hysterectomy, Proteobacteria phylum increased from 34.36% before surgery to 54.04% after surgery (p < 0.05). Conclusions: Although scientific literature reports different characterizations of intestinal microbiota in endometriotic patients, further evidence is needed to develop new diagnostic-therapeutic strategies, for example, administration with probiotics before surgery.}, }
@article {pmid36835535, year = {2023}, author = {Candel, S and Tyrkalska, SD and Pérez-Sanz, F and Moreno-Docón, A and Esteban, &#xc1; and Cayuela, ML and Mulero, V}, title = {Analysis of 16S rRNA Gene Sequence of Nasopharyngeal Exudate Reveals Changes in Key Microbial Communities Associated with Aging.}, journal = {International journal of molecular sciences}, volume = {24}, number = {4}, pages = {}, pmid = {36835535}, issn = {1422-0067}, support = {00006/COVI/20//Fundaci&#xf3;n S&#xe9;neca - Agencia de Ciencia y Tecnolog&#xed;a de la Regi&#xf3;n de Murcia/ ; }, mesh = {Male ; Female ; Humans ; RNA, Ribosomal, 16S/genetics ; Genes, rRNA ; Nasopharynx/microbiology ; *Microbiota/genetics ; Bacteria/genetics ; Aging ; *Virus Diseases/genetics ; }, abstract = {Functional or compositional perturbations of the microbiome can occur at different sites, of the body and this dysbiosis has been linked to various diseases. Changes in the nasopharyngeal microbiome are associated to patient's susceptibility to multiple viral infections, supporting the idea that the nasopharynx may be playing an important role in health and disease. Most studies on the nasopharyngeal microbiome have focused on a specific period in the lifespan, such as infancy or the old age, or have other limitations such as low sample size. Therefore, detailed studies analyzing the age- and sex-associated changes in the nasopharyngeal microbiome of healthy people across their whole life are essential to understand the relevance of the nasopharynx in the pathogenesis of multiple diseases, particularly viral infections. One hundred twenty nasopharyngeal samples from healthy subjects of all ages and both sexes were analyzed by 16S rRNA sequencing. Nasopharyngeal bacterial alpha diversity did not vary in any case between age or sex groups. Proteobacteria, Firmicutes, Actinobacteria, and Bacteroidetes were the predominant phyla in all the age groups, with several sex-associated. Acinetobacter, Brevundimonas, Dolosigranulum, Finegoldia, Haemophilus, Leptotrichia, Moraxella, Peptoniphilus, Pseudomonas, Rothia, and Staphylococcus were the only 11 bacterial genera that presented significant age-associated differences. Other bacterial genera such as Anaerococcus, Burkholderia, Campylobacter, Delftia, Prevotella, Neisseria, Propionibacterium, Streptococcus, Ralstonia, Sphingomonas, and Corynebacterium appeared in the population with a very high frequency, suggesting that their presence might be biologically relevant. Therefore, in contrast to other anatomical areas such as the gut, bacterial diversity in the nasopharynx of healthy subjects remains stable and resistant to perturbations throughout the whole life and in both sexes. Age-associated abundance changes were observed at phylum, family, and genus levels, as well as several sex-associated changes probably due to the different levels of sex hormones present in both sexes at certain ages. Our results provide a complete and valuable dataset that will be useful for future research aiming for studying the relationship between changes in the nasopharyngeal microbiome and susceptibility to or severity of multiple diseases.}, }
@article {pmid36835341, year = {2023}, author = {Brogna, C and Costanzo, V and Brogna, B and Bisaccia, DR and Brogna, G and Giuliano, M and Montano, L and Viduto, V and Cristoni, S and Fabrowski, M and Piscopo, M}, title = {Analysis of Bacteriophage Behavior of a Human RNA Virus, SARS-CoV-2, through the Integrated Approach of Immunofluorescence Microscopy, Proteomics and D-Amino Acid Quantification.}, journal = {International journal of molecular sciences}, volume = {24}, number = {4}, pages = {}, pmid = {36835341}, issn = {1422-0067}, mesh = {Humans ; SARS-CoV-2/genetics ; *COVID-19 ; RNA ; *Bacteriophages/genetics ; Amino Acids ; Proteomics ; *Viruses/genetics ; Microscopy, Fluorescence ; }, abstract = {SARS-CoV-2, one of the human RNA viruses, is widely studied around the world. Significant efforts have been made to understand its molecular mechanisms of action and how it interacts with epithelial cells and the human microbiome since it has also been observed in gut microbiome bacteria. Many studies emphasize the importance of surface immunity and also that the mucosal system is critical in the interaction of the pathogen with the cells of the oral, nasal, pharyngeal, and intestinal epithelium. Recent studies have shown how bacteria in the human gut microbiome produce toxins capable of altering the classical mechanisms of interaction of viruses with surface cells. This paper presents a simple approach to highlight the initial behavior of a novel pathogen, SARS-CoV-2, on the human microbiome. The immunofluorescence microscopy technique can be combined with spectral counting performed at mass spectrometry of viral peptides in bacterial cultures, along with identification of the presence of D-amino acids within viral peptides in bacterial cultures and in patients' blood. This approach makes it possible to establish the possible expression or increase of viral RNA viruses in general and SARS-CoV-2, as discussed in this study, and to determine whether or not the microbiome is involved in the pathogenetic mechanisms of the viruses. This novel combined approach can provide information more rapidly, avoiding the biases of virological diagnosis and identifying whether a virus can interact with, bind to, and infect bacteria and epithelial cells. Understanding whether some viruses have bacteriophagic behavior allows vaccine therapies to be focused either toward certain toxins produced by bacteria in the microbiome or toward finding inert or symbiotic viral mutations with the human microbiome. This new knowledge opens a scenario on a possible future vaccine: the probiotics vaccine, engineered with the right resistance to viruses that attach to both the epithelium human surface and gut microbiome bacteria.}, }
@article {pmid36817461, year = {2023}, author = {Sun, Y and Wen, M and Liu, Y and Wang, Y and Jing, P and Gu, Z and Jiang, T and Wang, W}, title = {The human microbiome: A promising target for lung cancer treatment.}, journal = {Frontiers in immunology}, volume = {14}, number = {}, pages = {1091165}, pmid = {36817461}, issn = {1664-3224}, mesh = {Humans ; Lung ; *Lung Neoplasms ; *Microbiota/physiology ; }, abstract = {Lung cancer is the leading cause of cancer-related deaths worldwide, and insights into its underlying mechanisms as well as potential therapeutic strategies are urgently needed. The microbiome plays an important role in human health, and is also responsible for the initiation and progression of lung cancer through its induction of inflammatory responses and participation in immune regulation, as well as for its role in the generation of metabolic disorders and genotoxicity. Here, the distribution of human microflora along with its biological functions, the relationship between the microbiome and clinical characteristics, and the role of the microbiome in clinical treatment of lung cancer were comprehensively reviewed. This review provides a basis for the current understanding of lung cancer mechanisms with a focus on the microbiome, and contributes to future decisions on treatment management.}, }
@article {pmid36811373, year = {2023}, author = {Mancini, VO and Brook, J and Hernandez, C and Strickland, D and Christophersen, CT and D'Vaz, N and Silva, D and Prescott, S and Callaghan, B and Downs, J and Finlay-Jones, A}, title = {Associations between the human immune system and gut microbiome with neurodevelopment in the first 5 years of life: A systematic scoping review.}, journal = {Developmental psychobiology}, volume = {65}, number = {2}, pages = {e22360}, pmid = {36811373}, issn = {1098-2302}, mesh = {Infant ; Child ; Humans ; *Gastrointestinal Microbiome ; Child Development ; Brain ; Immune System ; Biomarkers ; }, abstract = {The aim of this review was to map the literature assessing associations between maternal or infant immune or gut microbiome biomarkers and child neurodevelopmental outcomes within the first 5 years of life. We conducted a PRISMA-ScR compliant review of peer-reviewed, English-language journal articles. Studies reporting gut microbiome or immune system biomarkers and child neurodevelopmental outcomes prior to 5 years were eligible. Sixty-nine of 23,495 retrieved studies were included. Of these, 18 reported on the maternal immune system, 40 on the infant immune system, and 13 on the infant gut microbiome. No studies examined the maternal microbiome, and only one study examined biomarkers from both the immune system and the gut microbiome. Additionally, only one study included both maternal and infant biomarkers. Neurodevelopmental outcomes were assessed from 6 days to 5 years. Associations between biomarkers and neurodevelopmental outcomes were largely nonsignificant and small in effect size. While the immune system and gut microbiome are thought to have interactive impacts on the developing brain, there remains a paucity of published studies that report biomarkers from both systems and associations with child development outcomes. Heterogeneity of research designs and methodologies may also contribute to inconsistent findings. Future studies should integrate data across biological systems to generate novel insights into the biological underpinnings of early development.}, }
@article {pmid36803658, year = {2023}, author = {Wastyk, HC and Perelman, D and Topf, M and Fragiadakis, GK and Robinson, JL and Sonnenburg, JL and Gardner, CD and Sonnenburg, ED}, title = {Randomized controlled trial demonstrates response to a probiotic intervention for metabolic syndrome that may correspond to diet.}, journal = {Gut microbes}, volume = {15}, number = {1}, pages = {2178794}, pmid = {36803658}, issn = {1949-0984}, mesh = {Adult ; Humans ; *Metabolic Syndrome/drug therapy ; Prospective Studies ; *Gastrointestinal Microbiome/physiology ; *Probiotics ; Diet ; Double-Blind Method ; }, abstract = {An individual's immune and metabolic status is coupled to their microbiome. Probiotics offer a promising, safe route to influence host health, possibly via the microbiome. Here, we report an 18-week, randomized prospective study that explores the effects of a probiotic vs. placebo supplement on 39 adults with elevated parameters of metabolic syndrome. We performed longitudinal sampling of stool and blood to profile the human microbiome and immune system. While we did not see changes in metabolic syndrome markers in response to the probiotic across the entire cohort, there were significant improvements in triglycerides and diastolic blood pressure in a subset of probiotic arm participants. Conversely, the non-responders had increased blood glucose and insulin levels over time. The responders had a distinct microbiome profile at the end of the intervention relative to the non-responders and placebo arm. Importantly, diet was a key differentiating factor between responders and non-responders. Our results show participant-specific effects of a probiotic supplement on improving parameters of metabolic syndrome and suggest that dietary factors may enhance stability and efficacy of the supplement.}, }
@article {pmid36802215, year = {2023}, author = {Zangl, I and Beyer, R and Gattesco, A and Labuda, R and Pap, IJ and Strauss, J and Schüller, C}, title = {Limosilactobacillus fermentum Limits Candida glabrata Growth by Ergosterol Depletion.}, journal = {Microbiology spectrum}, volume = {11}, number = {2}, pages = {e0332622}, pmid = {36802215}, issn = {2165-0497}, abstract = {Candida glabrata is a human-associated opportunistic fungal pathogen. It shares its niche with Lactobacillus spp. in the gastrointestinal and vaginal tract. In fact, Lactobacillus species are thought to competitively prevent Candida overgrowth. We investigated the molecular aspects of this antifungal effect by analyzing the interaction of C. glabrata strains with Limosilactobacillus fermentum. From a collection of clinical C. glabrata isolates, we identified strains with different sensitivities to L. fermentum in coculture. We analyzed the variation of their expression pattern to isolate the specific response to L. fermentum. C. glabrata-L. fermentum coculture induced genes associated with ergosterol biosynthesis, weak acid stress, and drug/chemical stress. L. fermentum coculture depleted C. glabrata ergosterol. The reduction of ergosterol was dependent on the Lactobacillus species, even in coculture with different Candida species. We found a similar ergosterol-depleting effect with other lactobacillus strains (Lactobacillus crispatus and Lactobacillus rhamosus) on Candida albicans, Candida tropicalis, and Candida krusei. The addition of ergosterol improved C. glabrata growth in the coculture. Blocking ergosterol synthesis with fluconazole increased the susceptibility against L. fermentum, which was again mitigated by the addition of ergosterol. In accordance, a C. glabrata Δerg11 mutant, defective in ergosterol biosynthesis, was highly sensitive to L. fermentum. In conclusion, our analysis indicates an unexpected direct function of ergosterol for C. glabrata proliferation in coculture with L. fermentum. IMPORTANCE The yeast Candida glabrata, an opportunistic fungal pathogen, and the bacterium Limosilactobacillus fermentum both inhabit the human gastrointestinal and vaginal tract. Lactobacillus species, belonging to the healthy human microbiome, are thought to prevent C. glabrata infections. We investigated the antifungal effect of Limosilactobacillus fermentum on C. glabrata strains quantitively in vitro. The interaction between C. glabrata and L. fermentum evokes an upregulation of genes required for the synthesis of ergosterol, a sterol constituent of the fungal plasma membrane. We found a dramatic reduction of ergosterol in C. glabrata when it was exposed to L. fermentum. This effect extended to other Candida species and other Lactobacillus species. Furthermore, fungal growth was efficiently suppressed by a combination of L. fermentum and fluconazole, an antifungal drug which inhibits ergosterol synthesis. Thus, fungal ergosterol is a key metabolite for the suppression of C. glabrata by L. fermentum.}, }
@article {pmid36800400, year = {2023}, author = {Xing, Y and Clark, JR and Chang, JD and Chirman, DM and Green, S and Zulk, JJ and Jelinski, J and Patras, KA and Maresso, AW}, title = {Broad protective vaccination against systemic Escherichia coli with autotransporter antigens.}, journal = {PLoS pathogens}, volume = {19}, number = {2}, pages = {e1011082}, pmid = {36800400}, issn = {1553-7374}, support = {U19 AI144297/AI/NIAID NIH HHS/United States ; U19 AI157981/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Humans ; Mice ; Escherichia coli ; Type V Secretion Systems/genetics ; *Escherichia coli Infections/prevention &amp; control ; *Extraintestinal Pathogenic Escherichia coli/genetics ; Vaccination ; Virulence Factors/genetics ; Vaccines, Synthetic ; *Urinary Tract Infections/prevention &amp; control ; *Bacteremia/prevention &amp; control ; Immunoglobulin G/pharmacology ; }, abstract = {Extraintestinal pathogenic Escherichia coli (ExPEC) is the leading cause of adult life-threatening sepsis and urinary tract infections (UTI). The emergence and spread of multidrug-resistant (MDR) ExPEC strains result in a considerable amount of treatment failure and hospitalization costs, and contribute to the spread of drug resistance amongst the human microbiome. Thus, an effective vaccine against ExPEC would reduce morbidity and mortality and possibly decrease carriage in healthy or diseased populations. A comparative genomic analysis demonstrated a gene encoding an invasin-like protein, termed sinH, annotated as an autotransporter protein, shows high prevalence in various invasive ExPEC phylogroups, especially those associated with systemic bacteremia and UTI. Here, we evaluated the protective efficacy and immunogenicity of a recombinant SinH-based vaccine consisting of either domain-3 or domains-1,2, and 3 of the putative extracellular region of surface-localized SinH. Immunization of a murine host with SinH-based antigens elicited significant protection against various strains of the pandemic ExPEC sequence type 131 (ST131) as well as multiple sequence types in two distinct models of infection (colonization and bacteremia). SinH immunization also provided significant protection against ExPEC colonization in the bladder in an acute UTI model. Immunized cohorts produced significantly higher levels of vaccine-specific serum IgG and urinary IgG and IgA, findings consistent with mucosal protection. Collectively, these results demonstrate that autotransporter antigens such as SinH may constitute promising ExPEC phylogroup-specific and sequence-type effective vaccine targets that reduce E. coli colonization and virulence.}, }
@article {pmid36798240, year = {2023}, author = {Hall, B and Levy, S and Dufault-Thompson, K and Ndjite, GM and Weiss, A and Braccia, D and Jenkins, C and Yang, Y and Arp, G and Abeysinghe, S and Jermain, M and Wu, CH and Jiang, X}, title = {Discovery of the gut microbial enzyme responsible for bilirubin reduction to urobilinogen.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {36798240}, issn = {2692-8205}, support = {U54 DK110858/DK/NIDDK NIH HHS/United States ; }, abstract = {The degradation of heme and the interplay of its catabolic derivative, bilirubin, between humans and their gut microbiota is an essential facet of human health. However, the hypothesized bacterial enzyme that reduces bilirubin to urobilinogen, a key step that produces the excretable waste products of this pathway, has remained unidentified. In this study, we used a combination of biochemical analyses and comparative genomics to identify a novel enzyme, BilR, that can reduce bilirubin to urobilinogen. We delineated the BilR sequences from other members of the Old Yellow Enzyme family through the identification of key residues in the active site that are critical for bilirubin reduction and found that BilR is predominantly encoded by Firmicutes in the gut microbiome. Our analysis of human gut metagenomes showed that BilR is a common feature of a healthy adult human microbiome but has a decreased prevalence in neonates and IBD patients. This discovery sheds new light on the role of the gut microbiome in bilirubin metabolism and highlights the significance of the gut-liver axis in maintaining bilirubin homeostasis.}, }
@article {pmid36796332, year = {2023}, author = {Liu, YY}, title = {Controlling the human microbiome.}, journal = {Cell systems}, volume = {14}, number = {2}, pages = {135-159}, pmid = {36796332}, issn = {2405-4720}, support = {U19 AI095219/AI/NIAID NIH HHS/United States ; U01 HL089856/HL/NHLBI NIH HHS/United States ; RF1 AG067744/AG/NIA NIH HHS/United States ; R01 AI141529/AI/NIAID NIH HHS/United States ; R01 HD093761/HD/NICHD NIH HHS/United States ; UH3 OD023268/OD/NIH HHS/United States ; }, mesh = {Humans ; *Microbiota/genetics ; }, abstract = {We coexist with a vast number of microbes that live in and on our bodies. Those microbes and their genes are collectively known as the human microbiome, which plays important roles in human physiology and diseases. We have acquired extensive knowledge of the organismal compositions and metabolic functions of the human microbiome. However, the ultimate proof of our understanding of the human microbiome is reflected in our ability to manipulate it for health benefits. To facilitate the rational design of microbiome-based therapies, there are many fundamental questions to be addressed at the systems level. Indeed, we need a deep understanding of the ecological dynamics associated with such a complex ecosystem before we rationally design control strategies. In light of this, this review discusses progress from various fields, e.g., community ecology, network science, and control theory, that are helping us make progress toward the ultimate goal of controlling the human microbiome.}, }
@article {pmid36796148, year = {2023}, author = {Nami, Y and Haghshenas, B and Javanmard, A and Samari, M and Mohammadi, N and Oroojalian, F and Mokhtarzadeh, A}, title = {A critical review of the recent concept of artificial mechanical uterus design in relation to the maternal microbiome: An Update to past researches.}, journal = {Journal of reproductive immunology}, volume = {156}, number = {}, pages = {103828}, doi = {10.1016/j.jri.2023.103828}, pmid = {36796148}, issn = {1872-7603}, mesh = {Pregnancy ; Female ; Humans ; *Dysbiosis ; Infectious Disease Transmission, Vertical ; Uterus ; *Microbiota ; Vagina ; }, abstract = {The microbiome in the female reproductive tract plays an essential role in immune modulation and reproductive health. However, various microbes become established during pregnancy, the balance of which plays a crucial role in embryonic development and healthy births. The contribution of disturbances in the microbiome profile to embryo health is poorly understood. A better understanding of the relationship between reproductive outcomes and the vaginal microbiota is needed to optimize the chances of healthy births. In this regards, microbiome dysbiosis refers to conditions in which the pathways of communication and balance within the normal microbiome are imbalanced due to the intrusion of pathogenic microorganisms into the reproductive system. This review summarizes the current state of knowledge on the natural human microbiome, with a focus on the natural uterine microbiome, mother-to-child transmission, dysbiosis, and the pattern of microbial change in pregnancy and parturition, and reviews the effects of artificial uterus probiotics during pregnancy. These effects can be studied in the sterile environment of an artificial uterus, and microbes with potential probiotic activity can be studied as a possible therapeutic approach. The artificial uterus is a technological device or biobag used as an incubator, allowing extracorporeal pregnancy. Establishing beneficial microbial communities within the artificial womb using probiotic species could modulate the immune system of both the fetus and the mother. The artificial womb could be used to select the best strains of probiotic species to fight infection with specific pathogens. Questions about the interactions and stability of the most appropriate probiotics, as well as dosage and duration of treatment, need to be answered before probiotics can be a clinical treatment in human pregnancy.}, }
@article {pmid36790695, year = {2022}, author = {Rayo, E and Neukamm, J and Tomoum, N and Eppenberger, P and Breidenstein, A and Bouwman, AS and Schuenemann, VJ and Rühli, FJ}, title = {Metagenomic analysis of Ancient Egyptian canopic jars.}, journal = {American journal of biological anthropology}, volume = {179}, number = {2}, pages = {307-313}, pmid = {36790695}, issn = {2692-7691}, mesh = {Humans ; Egypt ; *DNA, Ancient ; *Mummies/pathology ; Lung ; Base Sequence ; }, abstract = {UNLABELLED: Ancient Egyptian remains have been of interest for anthropological research for decades. Despite many investigations, the ritual vessels for the internal organs removed during body preparation-liver, lungs, stomach, and intestines, of Egyptian mummies are rarely used for palaeopathological or medical investigations. These artifacts, commonly referred to as canopic jars, are the perfect combination of cultural and biological material and present an untapped resource for both Egyptological and medical fields. Nevertheless, technical challenges associated with this archeological material have prevented the application of current ancient DNA techniques for both the characterization of human and pathogenic DNA. We present shotgun-sequenced metagenomic profiles and ancient DNA degradation patterns from multiple canopic jars sampled from several European museum collections and enumerate current limitations and possible solutions for the future analysis of similar material. This is the first-ever recorded evidence of ancient human DNA found in Ancient Egyptian canopic jars and the first associated metagenomic description of bacterial taxa in these funerary artifacts.<br><br>OBJECTIVES: In this study, our objectives were to characterize the metagenomic profile of the Ancient Egyptian funerary vessels known as canopic jars to retrieve endogenous ancient human DNA, reconstruct ancient microbial communities, and identify possible pathogens that could shed light on disease states of individuals from the past.<br><br>METHODS: We applied ancient DNA techniques on 140 canopic jars to extract DNA and generate whole-genome sequencing libraries for the analysis of both human and bacterial DNA. The samples were obtained from museum collections in Berlin (DE), Burgdorf (DE), Leiden (NE), Manchester (UK), Munich (DE), St. Gallen (CH), Turin (IT), and Zagreb (HR).<br><br>RESULTS: Here we describe the first isolated DNA from the Egyptian artifacts that hold human viscera. No previous work was ever conducted on such material, which led to the first characterization of human DNA from Ancient Egyptian canopic jars and the profiling of the complex bacterial composition of this highly degraded, challenging, organic material. However, the DNA recovered was not of enough quality to confidently characterize bacterial taxa associated with infectious diseases, nor exclusive bacterial members of the human microbiome.<br><br>DISCUSSION: In summary, we present the first genomic survey of the visceral content of Ancient Egyptian funerary artifacts and demonstrate the limitations of current molecular methods to analyze canopic jars, such as the incomplete history of the objects or the presence of uncharacterized compounds that can hamper the recovery of DNA. Our work highlights the main challenges and caveats when working with such complicated archeological material - and offers sampling recommendations for similarly complex future studies, such as incrementing the amount of starting material and sampling from the less exposed parts of the jar content. This is the first-ever recorded evidence of ancient human DNA found in Ancient Egyptian canopic jars, and our results open new avenues in the study of neglected archeological artifacts.}, }
@article {pmid36778490, year = {2023}, author = {Zhu, B and Serrano, M and Buck, G}, title = {The influence of maternal factors on the neonatal microbiome and health.}, journal = {Research square}, volume = {}, number = {}, pages = {}, pmid = {36778490}, issn = {2693-5015}, abstract = {The human microbiome plays an essential role in human health. However, the influence of maternal factors on the neonatal microbiome remains obscure. Herein, our observations suggest that the neonatal buccal microbiome is similar to the maternal buccal microbiome, but the neonatal gastrointestinal microbiome develops a unique composition at an early stage. The low complexity of the neonatal buccal microbiome is a hallmark of maternal and neonatal health, but that of the neonatal gastrointestinal microbiome is associated with maternal inflammation-related metabolites. Microbial infections in the maternal reproductive tract universally impact the complexity of the neonatal microbiomes, and the body site is most important in modulating the composition of the neonatal microbiomes. Additionally, maternal lipids attenuated the adverse influence of several maternal factors on the neonatal microbiomes. Finally, admission of neonates to the newborn intensive care unit is associated with sub-optimal states of the maternal buccal and rectal microbiomes and maternal health.}, }
@article {pmid36778319, year = {2023}, author = {Wright, ML and Podnar, J and Longoria, KD and Nguyen, TC and Lim, S and Garcia, S and Wylie, D}, title = {Comparison of commercial DNA extraction kits for whole metagenome sequencing of human oral, vaginal, and rectal microbiome samples.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {36778319}, issn = {2692-8205}, support = {K01 NR017903/NR/NINR NIH HHS/United States ; }, abstract = {INTRODUCTION: Advancements in DNA extraction and sequencing technologies have been fundamental in deciphering the significance of the microbiome related to human health and pathology. Whole metagenome shotgun sequencing (WMS) is gaining popularity in use compared to its predecessor (i.e., amplicon-based approaches). However, like amplicon-based approaches, WMS is subject to bias from DNA extraction methods that can compromise the integrity of sequencing and subsequent findings. The purpose of this study was to evaluate systematic differences among four commercially available DNA extraction kits frequently used for WMS analysis of the microbiome.<br><br>METHODS: Oral, vaginal, and rectal swabs were collected in replicates of four by a healthcare provider from five participants and randomized to one of four DNA extraction kits. Two extraction blanks and three replicate mock community samples were also extracted using each extraction kit. WMS was completed with NovaSeq 6000 for all samples. Sequencing and microbial communities were analyzed using nonmetric multidimensional scaling and compositional bias analysis.<br><br>RESULTS: Extraction kits differentially biased the percentage of reads attributed to microbial taxa across samples and body sites. The PowerSoil Pro kit performed best in approximating expected proportions of mock communities. While HostZERO was biased against gram-negative bacteria, the kit outperformed other kits in extracting fungal DNA. In clinical samples, HostZERO yielded a smaller fraction of reads assigned to Homo sapiens across sites and had a higher fraction of reads assigned to bacterial taxa compared to other kits. However, HostZERO appears to bias representation of microbial communities and demonstrated the most dispersion by site, particularly for vaginal and rectal samples.<br><br>CONCLUSIONS: Systematic differences exist among four frequently referenced DNA extraction kits when used for WMS analysis of the human microbiome. Consideration of such differences in study design and data interpretation is imperative to safeguard the integrity of microbiome research and reproducibility of results.}, }
@article {pmid36776345, year = {2022}, author = {Osborne, N and Peterson, CB and Vannucci, M}, title = {Latent Network Estimation and Variable Selection for Compositional Data Via Variational EM.}, journal = {Journal of computational and graphical statistics : a joint publication of American Statistical Association, Institute of Mathematical Statistics, Interface Foundation of North America}, volume = {31}, number = {1}, pages = {163-175}, pmid = {36776345}, issn = {1061-8600}, support = {P30 CA016672/CA/NCI NIH HHS/United States ; }, abstract = {Network estimation and variable selection have been extensively studied in the statistical literature, but only recently have those two challenges been addressed simultaneously. In this article, we seek to develop a novel method to simultaneously estimate network interactions and associations to relevant covariates for count data, and specifically for compositional data, which have a fixed sum constraint. We use a hierarchical Bayesian model with latent layers and employ spike-and-slab priors for both edge and covariate selection. For posterior inference, we develop a novel variational inference scheme with an expectation-maximization step, to enable efficient estimation. Through simulation studies, we demonstrate that the proposed model outperforms existing methods in its accuracy of network recovery. We show the practical utility of our model via an application to microbiome data. The human microbiome has been shown to contribute too many of the functions of the human body, and also to be linked with a number of diseases. In our application, we seek to better understand the interaction between microbes and relevant covariates, as well as the interaction of microbes with each other. We call our algorithm simultaneous inference for networks and covariates and provide a Python implementation, which is available online.}, }
@article {pmid36774510, year = {2023}, author = {Cappello, C and Acin-Albiac, M and Pinto, D and Polo, A and Filannino, P and Rinaldi, F and Gobbetti, M and Di Cagno, R}, title = {Do nomadic lactobacilli fit as potential vaginal probiotics? The answer lies in a successful selective multi-step and scoring approach.}, journal = {Microbial cell factories}, volume = {22}, number = {1}, pages = {27}, pmid = {36774510}, issn = {1475-2859}, mesh = {Pregnancy ; Infant, Newborn ; Female ; Humans ; *Lactobacillus ; Bacterial Adhesion ; Vagina ; Candida albicans ; *Probiotics ; Inflammation ; }, abstract = {BACKGROUND: The goal of this study was to create a multi-strain probiotic gel that would foster a lactobacilli-dominated vaginal microbiota in pregnant women and ensure appropriate eubiosis for the newborn. Nomadic lactobacilli (95 strains), mostly isolated from food sources, were preliminarily screened for functional traits before being characterized for their capability to inhibit the two vaginal pathogens Streptococcus agalactiae and Candida albicans, which may lead to adverse pregnancy-related outcomes. Eight best-performing strains were chosen and furtherly investigated for their ability to produce biofilm. Lastly, the two selected potential probiotic candidates were analyzed in vitro for their ability to reduce the inflammation caused by C. albicans infection on the reconstituted human vaginal epithelium (HVE).<br><br>RESULTS: Lactiplantibacillus plantarum produced both isomers of lactic acid, while Lacticaseibacillus paracasei produced only L-isomer. The production of hydrogen peroxide was strain-dependent, with the highest concentrations found within Lact. paracasei strains. The auto-aggregation capacity and hydrophobicity traits were species-independent. S. agalactiae 88II3 was strongly inhibited both at pH 7.0 and 4.0, whereas the inhibition of C. albicans UNIBZ54 was less frequent. Overall, L. plantarum strains had the highest pathogen inhibition and functional scoring. L. plantarum C5 and POM1, which were selected as potential probiotic candidates also based on their ability to form biofilms, were able to counteract the inflammation process caused by C. albicans infection in the HVE model.<br><br>CONCLUSIONS: Our multi-step and cumulative scoring-based approach was proven successful in mining and highlighting the probiotic potential of two nomadic lactobacilli strains (L. plantarum C5 and POM1), being applicable to preserve and improve human vaginal health.}, }
@article {pmid36770726, year = {2023}, author = {Zhang, MN and Xie, R and Wang, HG and Wen, X and Wang, JY and He, L and Zhang, MH and Yang, XZ}, title = {Cepharanthine Alleviates DSS-Induced Ulcerative Colitis via Regulating Aconitate Decarboxylase 1 Expression and Macrophage Infiltration.}, journal = {Molecules (Basel, Switzerland)}, volume = {28}, number = {3}, pages = {}, pmid = {36770726}, issn = {1420-3049}, mesh = {Animals ; Mice ; Humans ; *Colitis, Ulcerative/chemically induced/drug therapy/metabolism ; Macrophages ; Colon/metabolism ; *Benzylisoquinolines/pharmacology ; Dextran Sulfate/toxicity ; Disease Models, Animal ; *Colitis/metabolism ; Mice, Inbred C57BL ; }, abstract = {Cepharanthine (CEP), a bisbenzylisoquinoline alkaloid from tubers of Stephania, protects against some inflammatory diseases. Aconitate decarboxylase 1 (ACOD1) is also known as immune-responsive gene 1 (IRG1), which plays an important immunometabolism role in inflammatory diseases by mediating the production of itaconic acid. ACOD1 exhibits abnormal expression in ulcerative colitis (UC). However, whether CEP can combat UC by affecting ACOD1 expression remains unanswered. This study was designed to explore the protective effects and mechanisms of CEP in treating colitis through in vitro and in vivo experiments. In vitro assays indicated that CEP inhibited LPS-induced secretion of pro-inflammatory cytokines and ACOD1 expression in RAW264.7 macrophages. Additionally, in the mouse model of DSS-induced colitis, CEP decreased macrophage infiltration and ACOD1 expression in colon tissue. After treatment with antibiotics (Abx), the expression of ACOD1 changed with the composition of gut microbiota. Correlation analysis also revealed that Family-XIII-AD3011-group and Rumini-clostridium-6 were positively correlated with ACOD1 expression level. Additionally, data of the integrative Human Microbiome Project (iHMP) showed that ACOD1 was highly expressed in the colon tissue of UC patients and this expression was positively correlated with the severity of intestinal inflammation. Collectively, CEP can counter UC by modulating gut microbiota and inhibiting the expression of ACOD1. CEP may serve as a potential pharmaceutical candidate in the treatment of UC.}, }
@article {pmid36769194, year = {2023}, author = {Campisciano, G and Zanotta, N and Quadrifoglio, M and Careri, A and Torresani, A and Cason, C and De Seta, F and Ricci, G and Comar, M and Stampalija, T}, title = {The Bacterial DNA Profiling of Chorionic Villi and Amniotic Fluids Reveals Overlaps with Maternal Oral, Vaginal, and Gut Microbiomes.}, journal = {International journal of molecular sciences}, volume = {24}, number = {3}, pages = {}, pmid = {36769194}, issn = {1422-0067}, support = {5MILLE15D5//Ministero della Salute/ ; }, mesh = {Pregnancy ; Female ; Humans ; *Amniotic Fluid ; Chorionic Villi ; *Gastrointestinal Microbiome ; DNA, Bacterial/genetics ; DNA Fingerprinting ; Bacteria/genetics ; Vagina/microbiology ; Cytokines/genetics ; }, abstract = {The in utero microbiome hypothesis has been long debated. This hypothesis will change our comprehension of the pioneer human microbiome if proved correct. In 60 uncomplicated pregnancies, we profiled the microbiome of chorionic villi (CV) and amniotic fluids (AF) in relation to maternal saliva, rectum, and vagina and the soluble cytokines cascade in the vagina, CV and AF. In our series, 12/37 (32%) AF and 10/23 (44%) CV tested positive for bacterial DNA. CV and AF harbored bacterial DNA of Streptococcus and Lactobacillus, overlapping that of the matched oral and vaginal niches, which showed a dysbiotic microbiome. In these pregnant women, the immune profiling revealed an immune hyporesponsiveness in the vagina and a high intraamniotic concentration of inflammatory cytokines. To understand the eventual role of bacterial colonization of the CV and AF and the associated immune response in the pregnancy outcome, further appropriate studies are needed. In this context, further studies should highlight if the hematogenous route could justify the spread of bacterial DNA from the oral microbiome to the placenta and if vaginal dysbiosis could favor the likelihood of identifying CV and AF positive for bacterial DNA.}, }
@article {pmid36765892, year = {2023}, author = {Piao, XM and Byun, YJ and Zheng, CM and Song, SJ and Kang, HW and Kim, WT and Yun, SJ}, title = {A New Treatment Landscape for RCC: Association of the Human Microbiome with Improved Outcomes in RCC.}, journal = {Cancers}, volume = {15}, number = {3}, pages = {}, pmid = {36765892}, issn = {2072-6694}, support = {2020R1I1A3062508//National Research Foundation of Korea/ ; 2021R1I1A1A01050891//National Research Foundation of Korea/ ; 2021RIS-001(1345341783)//National Research Foundation of Korea/ ; //MD-Phd/Medical Scientist Training Program through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health &amp; Welfare, Republic of Korea./ ; }, abstract = {Microbes play different roles in metabolism, local or systemic inflammation, and immunity, and the human microbiome in tumor microenvironment (TME) is important for modulating the response to immunotherapy in cancer patients. Renal cell carcinoma (RCC) is an immunogenic tumor, and immunotherapy is the backbone of its treatment. Correlations between the microbiome and responsiveness to immune checkpoint inhibitors have been reported. This review summarizes the recent therapeutic strategies for RCC and the effects of TME on the systemic therapy of RCC. The current understanding and advances in microbiome research and the relationship between the microbiome and the response to immunotherapy for RCC are also discussed. Improving our understanding of the role of the microbiome in RCC treatment will facilitate the development of microbiome targeting therapies to modify the tumor microbiome and improve treatment outcomes.}, }
@article {pmid36760501, year = {2023}, author = {Schackart, KE and Graham, JB and Ponsero, AJ and Hurwitz, BL}, title = {Evaluation of computational phage detection tools for metagenomic datasets.}, journal = {Frontiers in microbiology}, volume = {14}, number = {}, pages = {1078760}, pmid = {36760501}, issn = {1664-302X}, support = {T32 GM132008/GM/NIGMS NIH HHS/United States ; T34 GM008718/GM/NIGMS NIH HHS/United States ; }, abstract = {INTRODUCTION: As new computational tools for detecting phage in metagenomes are being rapidly developed, a critical need has emerged to develop systematic benchmarks.<br><br>METHODS: In this study, we surveyed 19 metagenomic phage detection tools, 9 of which could be installed and run at scale. Those 9 tools were assessed on several benchmark challenges. Fragmented reference genomes are used to assess the effects of fragment length, low viral content, phage taxonomy, robustness to eukaryotic contamination, and computational resource usage. Simulated metagenomes are used to assess the effects of sequencing and assembly quality on the tool performances. Finally, real human gut metagenomes and viromes are used to assess the differences and similarities in the phage communities predicted by the tools.<br><br>RESULTS: We find that the various tools yield strikingly different results. Generally, tools that use a homology approach (VirSorter, MARVEL, viralVerify, VIBRANT, and VirSorter2) demonstrate low false positive rates and robustness to eukaryotic contamination. Conversely, tools that use a sequence composition approach (VirFinder, DeepVirFinder, Seeker), and MetaPhinder, have higher sensitivity, including to phages with less representation in reference databases. These differences led to widely differing predicted phage communities in human gut metagenomes, with nearly 80% of contigs being marked as phage by at least one tool and a maximum overlap of 38.8% between any two tools. While the results were more consistent among the tools on viromes, the differences in results were still significant, with a maximum overlap of 60.65%. Discussion: Importantly, the benchmark datasets developed in this study are publicly available and reusable to enable the future comparability of new tools developed.}, }
@article {pmid36754953, year = {2023}, author = {Wang, Y and Wang, L and Sun, T and Shen, S and Li, Z and Ma, X and Gu, X and Zhang, X and Peng, A and Xu, X and Feng, Q}, title = {Study of the inflammatory activating process in the early stage of Fusobacterium nucleatum infected PDLSCs.}, journal = {International journal of oral science}, volume = {15}, number = {1}, pages = {8}, pmid = {36754953}, issn = {2049-3169}, mesh = {Humans ; *Fusobacterium nucleatum/metabolism ; NF-kappa B/metabolism ; Periodontal Ligament/metabolism ; Signal Transduction ; *Fusobacterium Infections/metabolism/microbiology/pathology ; Stem Cells/metabolism ; }, abstract = {Fusobacterium nucleatum (F. nucleatum) is an early pathogenic colonizer in periodontitis, but the host response to infection with this pathogen remains unclear. In this study, we built an F. nucleatum infectious model with human periodontal ligament stem cells (PDLSCs) and showed that F. nucleatum could inhibit proliferation, and facilitate apoptosis, ferroptosis, and inflammatory cytokine production in a dose-dependent manner. The F. nucleatum adhesin FadA acted as a proinflammatory virulence factor and increased the expression of interleukin(IL)-1β, IL-6 and IL-8. Further study showed that FadA could bind with PEBP1 to activate the Raf1-MAPK and IKK-NF-κB signaling pathways. Time-course RNA-sequencing analyses showed the cascade of gene activation process in PDLSCs with increasing durations of F. nucleatum infection. NFκB1 and NFκB2 upregulated after 3 h of F. nucleatum-infection, and the inflammatory-related genes in the NF-κB signaling pathway were serially elevated with time. Using computational drug repositioning analysis, we predicted and validated that two potential drugs (piperlongumine and fisetin) could attenuate the negative effects of F. nucleatum-infection. Collectively, this study unveils the potential pathogenic mechanisms of F. nucleatum and the host inflammatory response at the early stage of F. nucleatum infection.}, }
@article {pmid36744900, year = {2023}, author = {Bhandari, P and Tingley, J and Abbott, DW and Hill, JE}, title = {Glycogen-Degrading Activities of Catalytic Domains of α-Amylase and α-Amylase-Pullulanase Enzymes Conserved in Gardnerella spp. from the Vaginal Microbiome.}, journal = {Journal of bacteriology}, volume = {205}, number = {2}, pages = {e0039322}, pmid = {36744900}, issn = {1098-5530}, support = {//Gouvernement du Canada | Natural Sciences and Engineering Research Council of Canada (NSERC)/ ; }, mesh = {Female ; Humans ; alpha-Amylases/metabolism ; Bacteria/metabolism ; Catalytic Domain ; Gardnerella ; Glycogen/metabolism ; Maltose ; *Microbiota ; *Premature Birth ; Vagina/microbiology ; *Vaginosis, Bacterial/microbiology ; }, abstract = {Gardnerella spp. are associated with bacterial vaginosis in which normally dominant lactobacilli are replaced with facultative and anaerobic bacteria, including Gardnerella spp. Co-occurrence of multiple species of Gardnerella is common in the vagina, and competition for nutrients such as glycogen likely contributes to the differential abundances of Gardnerella spp. Glycogen must be digested into smaller components for uptake, a process that depends on the combined action of glycogen-degrading enzymes. In this study, the ability of culture supernatants of 15 isolates of Gardnerella spp. to produce glucose, maltose, maltotriose, and maltotetraose from glycogen was demonstrated. Carbohydrate-active enzymes (CAZymes) were identified bioinformatically in Gardnerella proteomes using dbCAN2. Identified proteins included a single-domain α-amylase (EC 3.2.1.1) (encoded by all 15 isolates) and an α-amylase-pullulanase (EC 3.2.1.41) containing amylase, carbohydrate binding modules, and pullulanase domains (14/15 isolates). To verify the sequence-based functional predictions, the amylase and pullulanase domains of the α-amylase-pullulanase and the single-domain α-amylase were each produced in Escherichia coli. The α-amylase domain from the α-amylase-pullulanase released maltose, maltotriose, and maltotetraose from glycogen, and the pullulanase domain released maltotriose from pullulan and maltose from glycogen, demonstrating that the Gardnerella α-amylase-pullulanase is capable of hydrolyzing α-1,4 and α-1,6 glycosidic bonds. Similarly, the single-domain α-amylase protein also produced maltose, maltotriose, and maltotetraose from glycogen. Our findings show that Gardnerella spp. produce extracellular amylase enzymes as "public goods" that can digest glycogen into maltose, maltotriose, and maltotetraose that can be used by the vaginal microbiota. IMPORTANCE Increased abundance of Gardnerella spp. is a diagnostic characteristic of bacterial vaginosis, an imbalance in the human vaginal microbiome associated with troubling symptoms, and negative reproductive health outcomes, including increased transmission of sexually transmitted infections and preterm birth. Competition for nutrients is likely an important factor in causing dramatic shifts in the vaginal microbial community, but little is known about the contribution of bacterial enzymes to the metabolism of glycogen, a major food source available to vaginal bacteria. The significance of our research is characterizing the activity of enzymes conserved in Gardnerella species that contribute to the ability of these bacteria to utilize glycogen.}, }
@article {pmid36741465, year = {2022}, author = {Cobo-López, S and Gupta, VK and Sung, J and Guimerà, R and Sales-Pardo, M}, title = {Stochastic block models reveal a robust nested pattern in healthy human gut microbiomes.}, journal = {PNAS nexus}, volume = {1}, number = {3}, pages = {pgac055}, pmid = {36741465}, issn = {2752-6542}, abstract = {A key question in human gut microbiome research is what are the robust structural patterns underlying its taxonomic composition. Herein, we use whole metagenomic datasets from healthy human guts to show that such robust patterns do exist, albeit not in the conventional enterotype sense. We first introduce the concept of mixed-membership enterotypes using a network inference approach based on stochastic block models. We find that gut microbiomes across a group of people (hosts) display a nested structure, which has been observed in a number of ecological systems. This finding led us to designate distinct ecological roles to both microbes and hosts: generalists and specialists. Specifically, generalist hosts have microbiomes with most microbial species, while specialist hosts only have generalist microbes. Moreover, specialist microbes are only present in generalist hosts. From the nested structure of microbial taxonomies, we show that these ecological roles of microbes are generally conserved across datasets. Our results show that the taxonomic composition of healthy human gut microbiomes is associated with robustly structured combinations of generalist and specialist species.}, }
@article {pmid36736005, year = {2023}, author = {Fujiyoshi, S and Yarimizu, K and Perera, I and Abanto, M and Jorquera, M and Maruyama, F}, title = {Learning from mistakes: challenges in finding holobiont factors from environmental samples and the importance of methodological consistency.}, journal = {Current opinion in biotechnology}, volume = {80}, number = {}, pages = {102897}, doi = {10.1016/j.copbio.2023.102897}, pmid = {36736005}, issn = {1879-0429}, mesh = {Humans ; *Harmful Algal Bloom ; *Bacteria ; Environmental Monitoring ; }, abstract = {The cause of harmful algal blooms has been a mystery, but research to elucidate its mechanism has progressed over the years thanks to genetic technologies. We have monitored toxic algae and its associated bacteria as a community, the so-called 'holobiont' in Chilean coastal waters for years from the perspective of bacteria as an algal bloom driver. This review describes the challenges of holobiont monitoring, specifically with respect to standardizing and compliance with the monitoring protocols to collect reliable and sustainable data. Further, we suggest adopting the high-throughput sequencing (HTS) standard operating procedure (SOP) by the International Human Microbiome to improve the quality and consistency of holobiont monitoring in the harmful algal world.}, }
@article {pmid36728456, year = {2023}, author = {Markkanen, MA and Haukka, K and Pärnänen, KMM and Dougnon, VT and Bonkoungou, IJO and Garba, Z and Tinto, H and Sarekoski, A and Karkman, A and Kantele, A and Virta, MPJ}, title = {Metagenomic Analysis of the Abundance and Composition of Antibiotic Resistance Genes in Hospital Wastewater in Benin, Burkina Faso, and Finland.}, journal = {mSphere}, volume = {8}, number = {1}, pages = {e0053822}, pmid = {36728456}, issn = {2379-5042}, mesh = {Humans ; *Anti-Bacterial Agents/pharmacology ; *Wastewater ; Burkina Faso ; Benin ; Finland ; Drug Resistance, Microbial/genetics ; Hospitals ; }, abstract = {Antibiotic resistance is a global threat to human health, with the most severe effect in low- and middle-income countries. We explored the presence of antibiotic resistance genes (ARGs) in the hospital wastewater (HWW) of nine hospitals in Benin and Burkina Faso, two low-income countries in West Africa, with shotgun metagenomic sequencing. For comparison, we also studied six hospitals in Finland. The highest sum of the relative abundance of ARGs in the 68 HWW samples was detected in Benin and the lowest in Finland. HWW resistomes and mobilomes in Benin and Burkina Faso resembled each other more than those in Finland. Many carbapenemase genes were detected at various abundances, especially in HWW from Burkina Faso and Finland. The blaGES genes, the most widespread carbapenemase gene in the Beninese HWW, were also found in water intended for hand washing and in a puddle at a hospital yard in Benin. mcr genes were detected in the HWW of all three countries, with mcr-5 being the most common mcr gene. These and other mcr genes were observed in very high relative abundances, even in treated wastewater in Burkina Faso and a street gutter in Benin. The results highlight the importance of wastewater treatment, with particular attention to HWW. IMPORTANCE The global emergence and increased spread of antibiotic resistance threaten the effectiveness of antibiotics and, thus, the health of the entire population. Therefore, understanding the resistomes in different geographical locations is crucial in the global fight against the antibiotic resistance crisis. However, this information is scarce in many low- and middle-income countries (LMICs), such as those in West Africa. In this study, we describe the resistomes of hospital wastewater in Benin and Burkina Faso and, as a comparison, Finland. Our results help to understand the hitherto unrevealed resistance in Beninese and Burkinabe hospitals. Furthermore, the results emphasize the importance of wastewater management infrastructure design to minimize exposure events between humans, HWW, and the environment, preventing the circulation of resistant bacteria and ARGs between humans (hospitals and community) and the environment.}, }
@article {pmid36726632, year = {2022}, author = {Legba, BB and Dougnon, V and Koudokpon, H and Mero, S and Elovainio, R and Parry, M and Bankole, H and Haukka, K}, title = {Assessment of blood cultures and antibiotic susceptibility testing for bacterial sepsis diagnosis and utilization of results by clinicians in Benin: A qualitative study.}, journal = {Frontiers in public health}, volume = {10}, number = {}, pages = {1088590}, pmid = {36726632}, issn = {2296-2565}, mesh = {Humans ; *Blood Culture ; Benin ; Microbial Sensitivity Tests ; *Sepsis/diagnosis/drug therapy ; Anti-Bacterial Agents/pharmacology/therapeutic use ; Escherichia coli ; }, abstract = {OBJECTIVES: We assessed the current status of blood culture and antibiotic susceptibility testing (AST) practices in clinical laboratories in Benin, and how the laboratory results are used by physicians to prescribe antibiotics.<br><br>METHODS: The qualitative study covered twenty-five clinical laboratories with a bacteriology unit and associated hospitals and pharmacies. Altogether 159 laboratory staff, physicians and pharmacists were interviewed about their perceptions of the state of laboratory diagnostics related to sepsis and the use of antibiotics. Face-to-face interviews based on structured questionnaires were supported by direct observations when visiting five laboratories in across the country.<br><br>RESULTS: Only 6 laboratories (24%) conducted blood cultures, half of them with a maximum of 10 samples per month. The most common gram-negative bacteria isolated from blood cultures were: Escherichia coli, Salmonella spp. and Salmonella enterica serovar Typhi while the most common gram-positives were Enterococcus spp. and Staphylococcus aureus. None of the laboratories listed Klebsiella pneumoniae among the three most common bacteria isolated from blood cultures, although other evidence indicates that it is the most common cause of sepsis in Benin. Due to limited testing capacity, physicians most commonly use empirical antibiotic therapy.<br><br>CONCLUSIONS: More resources are needed to develop laboratory testing capacity, technical skills in bacterial identification, AST, quality assurance, and communication of results must be strengthened.}, }
@article {pmid36725208, year = {2023}, author = {Walsh, AM and Leech, J and Huttenhower, C and Delhomme-Nguyen, H and Crispie, F and Chervaux, C and Cotter, PD}, title = {Integrated molecular approaches for fermented food microbiome research.}, journal = {FEMS microbiology reviews}, volume = {47}, number = {2}, pages = {}, pmid = {36725208}, issn = {1574-6976}, mesh = {Animals ; Humans ; *Microbiota ; Diet ; *Fermented Foods ; Fermentation ; High-Throughput Nucleotide Sequencing ; }, abstract = {Molecular technologies, including high-throughput sequencing, have expanded our perception of the microbial world. Unprecedented insights into the composition and function of microbial communities have generated large interest, with numerous landmark studies published in recent years relating the important roles of microbiomes and the environment-especially diet and nutrition-in human, animal, and global health. As such, food microbiomes represent an important cross-over between the environment and host. This is especially true of fermented food microbiomes, which actively introduce microbial metabolites and, to a lesser extent, live microbes into the human gut. Here, we discuss the history of fermented foods, and examine how molecular approaches have advanced research of these fermented foods over the past decade. We highlight how various molecular approaches have helped us to understand the ways in which microbes shape the qualities of these products, and we summarize the impacts of consuming fermented foods on the gut. Finally, we explore how advances in bioinformatics could be leveraged to enhance our understanding of fermented foods. This review highlights how integrated molecular approaches are changing our understanding of the microbial communities associated with food fermentation, the creation of unique food products, and their influences on the human microbiome and health.}, }
@article {pmid36721396, year = {2023}, author = {SeyedAlinaghi, S and Afzalian, A and Pashaei, Z and Varshochi, S and Karimi, A and Mojdeganlou, H and Mojdeganlou, P and Razi, A and Ghanadinezhad, F and Shojaei, A and Amiri, A and Dashti, M and Ghasemzadeh, A and Dadras, O and Mehraeen, E and Afsahi, AM}, title = {Gut microbiota and COVID-19: A systematic review.}, journal = {Health science reports}, volume = {6}, number = {2}, pages = {e1080}, pmid = {36721396}, issn = {2398-8835}, abstract = {BACKGROUND AND AIMS: Alteration in humans' gut microbiota was reported in patients infected with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). The gut and upper respiratory tract (URT) microbiota harbor a dynamic and complex population of microorganisms and have strong interaction with host immune system homeostasis. However, our knowledge about microbiota and its association with SARS-CoV-2 is still limited. We aimed to systematically review the effects of gut microbiota on the SARS-CoV-2 infection and its severity and the impact that SARS-CoV-2 could have on the gut microbiota.<br><br>METHODS: We searched the keywords in the online databases of Web of Science, Scopus, PubMed, and Cochrane on December 31, 2021. After duplicate removal, we performed the screening process in two stages; title/abstract and then full-text screening. The data of the eligible studies were extracted into a pre-designed word table. This study adhered to the PRISMA checklist and Newcastle-Ottawa Scale Bias Assessment tool.<br><br>RESULTS: Sixty-three publications were included in this review. Our study shows that among COVID-19 patients, particularly moderate to severe cases, the gut and lung microbiota was different compared to healthy individuals. In addition, the severity, and viral load of COVID-19 disease would probably also be influenced by the gut, and lung microbiota's composition.<br><br>CONCLUSION: Our study concludes that there was a significant difference in the composition of the URT, and gut microbiota in COVID-19 patients compared to the general healthy individuals, with an increase in opportunistic pathogens. Further, research is needed to investigate the probable bidirectional association of COVID-19 and human microbiome.}, }
@article {pmid36720857, year = {2023}, author = {Pruss, KM and Chen, H and Liu, Y and Van Treuren, W and Higginbottom, SK and Jarman, JB and Fischer, CR and Mak, J and Wong, B and Cowan, TM and Fischbach, MA and Sonnenburg, JL and Dodd, D}, title = {Host-microbe co-metabolism via MCAD generates circulating metabolites including hippuric acid.}, journal = {Nature communications}, volume = {14}, number = {1}, pages = {512}, pmid = {36720857}, issn = {2041-1723}, support = {R01 DK101674/DK/NIDDK NIH HHS/United States ; R01 AT011396/AT/NCCIH NIH HHS/United States ; K08 DK110335/DK/NIDDK NIH HHS/United States ; R01 DK085025/DK/NIDDK NIH HHS/United States ; R35 GM142873/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Female ; Humans ; Male ; Mice ; Acyl-CoA Dehydrogenase ; *Hippurates ; *Metabolomics ; Phenylalanine ; }, abstract = {The human gut microbiota produces dozens of small molecules that circulate in blood, accumulate to comparable levels as pharmaceutical drugs, and influence host physiology. Despite the importance of these metabolites to human health and disease, the origin of most microbially-produced molecules and their fate in the host remains largely unknown. Here, we uncover a host-microbe co-metabolic pathway for generation of hippuric acid, one of the most abundant organic acids in mammalian urine. Combining stable isotope tracing with bacterial and host genetics, we demonstrate reduction of phenylalanine to phenylpropionic acid by gut bacteria; the host re-oxidizes phenylpropionic acid involving medium-chain acyl-CoA dehydrogenase (MCAD). Generation of germ-free male and female MCAD[-/-] mice enabled gnotobiotic colonization combined with untargeted metabolomics to identify additional microbial metabolites processed by MCAD in host circulation. Our findings uncover a host-microbe pathway for the abundant, non-toxic phenylalanine metabolite hippurate and identify β-oxidation via MCAD as a novel mechanism by which mammals metabolize microbiota-derived metabolites.}, }
@article {pmid36711684, year = {2023}, author = {Wilson, NG and Hernandez-Leyva, A and Schwartz, DJ and Bacharier, LB and Kau, AL}, title = {The gut metagenome harbors metabolic and antibiotic resistance signatures of moderate-to-severe asthma.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {36711684}, issn = {2692-8205}, support = {F30 DK127584/DK/NIDDK NIH HHS/United States ; K08 AI113184/AI/NIAID NIH HHS/United States ; T32 GM007200/GM/NIGMS NIH HHS/United States ; }, abstract = {Asthma is a common allergic airway disease that develops in association with the human microbiome early in life. Both the composition and function of the infant gut microbiota have been linked to asthma risk, but functional alterations in the gut microbiota of older patients with established asthma remain an important knowledge gap. Here, we performed whole metagenomic shotgun sequencing of 95 stool samples from 59 healthy and 36 subjects with moderate-to-severe asthma to characterize the metagenomes of gut microbiota in children and adults 6 years and older. Mapping of functional orthologs revealed that asthma contributes to 2.9% of the variation in metagenomic content even when accounting for other important clinical demographics. Differential abundance analysis showed an enrichment of long-chain fatty acid (LCFA) metabolism pathways which have been previously implicated in airway smooth muscle and immune responses in asthma. We also observed increased richness of antibiotic resistance genes (ARGs) in people with asthma. One differentially abundant ARG was a macrolide resistance marker, ermF, which significantly co-occurred with the Bacteroides fragilis toxin, suggesting a possible relationship between enterotoxigenic B. fragilis, antibiotic resistance, and asthma. Lastly, we found multiple virulence factor (VF) and ARG pairs that co-occurred in both cohorts suggesting that virulence and antibiotic resistance traits are co-selected and maintained in the fecal microbiota of people with asthma. Overall, our results show functional alterations via LCFA biosynthetic genes and increases in antibiotic resistance genes in the gut microbiota of subjects with moderate-to-severe asthma and could have implications for asthma management and treatment.}, }
@article {pmid36702753, year = {2023}, author = {Sun, H and Wang, Y and Xiao, Z and Huang, X and Wang, H and He, T and Jiang, X}, title = {multiMiAT: an optimal microbiome-based association test for multicategory phenotypes.}, journal = {Briefings in bioinformatics}, volume = {24}, number = {2}, pages = {}, doi = {10.1093/bib/bbad012}, pmid = {36702753}, issn = {1477-4054}, mesh = {Humans ; *Microbiota/genetics ; Computer Simulation ; Phenotype ; *Gastrointestinal Microbiome ; Logistic Models ; }, abstract = {Microbes can affect the metabolism and immunity of human body incessantly, and the dysbiosis of human microbiome drives not only the occurrence but also the progression of disease (i.e. multiple statuses of disease). Recently, microbiome-based association tests have been widely developed to detect the association between the microbiome and host phenotype. However, the existing methods have not achieved satisfactory performance in testing the association between the microbiome and ordinal/nominal multicategory phenotypes (e.g. disease severity and tumor subtype). In this paper, we propose an optimal microbiome-based association test for multicategory phenotypes, namely, multiMiAT. Specifically, under the multinomial logit model framework, we first introduce a microbiome regression-based kernel association test for multicategory phenotypes (multiMiRKAT). As a data-driven optimal test, multiMiAT then integrates multiMiRKAT, score test and MiRKAT-MC to maintain excellent performance in diverse association patterns. Massive simulation experiments prove the success of our method. Furthermore, multiMiAT is also applied to real microbiome data experiments to detect the association between the gut microbiome and clinical statuses of colorectal cancer as well as for diverse statuses of Clostridium difficile infections.}, }
@article {pmid36697862, year = {2023}, author = {Kennedy, KM and de Goffau, MC and Perez-Muñoz, ME and Arrieta, MC and Bäckhed, F and Bork, P and Braun, T and Bushman, FD and Dore, J and de Vos, WM and Earl, AM and Eisen, JA and Elovitz, MA and Ganal-Vonarburg, SC and Gänzle, MG and Garrett, WS and Hall, LJ and Hornef, MW and Huttenhower, C and Konnikova, L and Lebeer, S and Macpherson, AJ and Massey, RC and McHardy, AC and Koren, O and Lawley, TD and Ley, RE and O'Mahony, L and O'Toole, PW and Pamer, EG and Parkhill, J and Raes, J and Rattei, T and Salonen, A and Segal, E and Segata, N and Shanahan, F and Sloboda, DM and Smith, GCS and Sokol, H and Spector, TD and Surette, MG and Tannock, GW and Walker, AW and Yassour, M and Walter, J}, title = {Questioning the fetal microbiome illustrates pitfalls of low-biomass microbial studies.}, journal = {Nature}, volume = {613}, number = {7945}, pages = {639-649}, pmid = {36697862}, issn = {1476-4687}, support = {BBS/E/F/00044409/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; R01 HD102318/HD/NICHD NIH HHS/United States ; P30 AI045008/AI/NIAID NIH HHS/United States ; R01 CA219871/CA/NCI NIH HHS/United States ; /WT_/Wellcome Trust/United Kingdom ; 100974/C/13/Z/WT_/Wellcome Trust/United Kingdom ; 220876/Z/20/Z/WT_/Wellcome Trust/United Kingdom ; R01 AI139240/AI/NIAID NIH HHS/United States ; MR/K021133/1/MRC_/Medical Research Council/United Kingdom ; BBS/E/F/000PR10353/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; R01 NR014784/NR/NINR NIH HHS/United States ; BBS/E/F/000PR10356/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; R01 AI120489/AI/NIAID NIH HHS/United States ; R01 HD098867/HD/NICHD NIH HHS/United States ; R33 HL137063/HL/NHLBI NIH HHS/United States ; U19 AI110818/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Female ; Humans ; Pregnancy ; Amniotic Fluid/immunology/microbiology ; *Biomass ; Mammals ; *Microbiota/genetics ; Placenta/immunology/microbiology ; *Fetus/immunology/microbiology ; *DNA Contamination ; Reproducibility of Results ; }, abstract = {Whether the human fetus and the prenatal intrauterine environment (amniotic fluid and placenta) are stably colonized by microbial communities in a healthy pregnancy remains a subject of debate. Here we evaluate recent studies that characterized microbial populations in human fetuses from the perspectives of reproductive biology, microbial ecology, bioinformatics, immunology, clinical microbiology and gnotobiology, and assess possible mechanisms by which the fetus might interact with microorganisms. Our analysis indicates that the detected microbial signals are likely the result of contamination during the clinical procedures to obtain fetal samples or during DNA extraction and DNA sequencing. Furthermore, the existence of live and replicating microbial populations in healthy fetal tissues is not compatible with fundamental concepts of immunology, clinical microbiology and the derivation of germ-free mammals. These conclusions are important to our understanding of human immune development and illustrate common pitfalls in the microbial analyses of many other low-biomass environments. The pursuit of a fetal microbiome serves as a cautionary example of the challenges of sequence-based microbiome studies when biomass is low or absent, and emphasizes the need for a trans-disciplinary approach that goes beyond contamination controls by also incorporating biological, ecological and mechanistic concepts.}, }
@article {pmid36696240, year = {2022}, author = {Pang, Z and Korpela, R and Vapaatalo, H}, title = {Intestinal aldosterone synthase activity and aldosterone synthesis in mouse.}, journal = {Journal of physiology and pharmacology : an official journal of the Polish Physiological Society}, volume = {73}, number = {4}, pages = {}, doi = {10.26402/jpp.2022.4.03}, pmid = {36696240}, issn = {1899-1505}, mesh = {Mice ; Animals ; *Cytochrome P-450 CYP11B2/genetics ; *Aldosterone/metabolism ; Corticosterone/metabolism ; }, abstract = {Aldosterone is the most important mineralocorticoid hormone regulating water and electrolyte absorption in the distal convoluted tubule of the kidney. Recently, we detected the presence of the whole chain of aldosterone production from the precursor corticosterone, transcription factor liver receptor homologue-1 (LRH-1), the aldosterone synthase enzyme protein (CYP11B2) as well as the gene to the final product aldosterone in murine large intestine. Here, we decided to correlate the amount of this synthase protein with its enzymatic activity in different parts of gastrointestinal tract and also with the aldosterone concentration in the respective tissue. Considering the physiological behavior of the animals in light and dark environment, we measured these variables at four time points - two in the light, the others during darkness. In vitro activity of CYP11B2 was measured as the amount of aldosterone formed from the precursor deoxycorticosterone using enzyme preparations from homogenized intestinal sections. CYP11B2 enzyme activity was higher in the large than in the small intestine. In ileum and colon, the CYP11B2 activity increased in the dark time. The highest aldosterone concentration was detected in the dark in the large intestine. In summary, enzyme activity of CYP11B2 was present in all parts of intestine; the large intestine formed more aldosterone during the darkness. No difference was seen in any of the variables between the early and late light hours.}, }
@article {pmid36681812, year = {2023}, author = {Gardemeister, S and Skogberg, K and Saisto, T and Salonen, A and de Vos, WM and Korpela, K and Kolho, KL}, title = {Cross-sectional study of the proportion of antibiotic use during childbirth in full-term deliveries in Finland.}, journal = {BMC pregnancy and childbirth}, volume = {23}, number = {1}, pages = {50}, pmid = {36681812}, issn = {1471-2393}, mesh = {Pregnancy ; Infant ; Female ; Humans ; *Anti-Bacterial Agents/therapeutic use ; Cross-Sectional Studies ; Cohort Studies ; Finland ; *Antibiotic Prophylaxis ; }, abstract = {PURPOSE: In developed countries, data on the frequency of antibiotics given to mothers during childbirth are limited beyond the overall effect of all various prophylactic indications. Also, data on the impact of such antibiotics to the well-being of term babies are scarce. We aimed to characterize the frequency of antibiotic use during childbirth of term pregnancy. Secondly, we assessed whether the use of antibiotics was associated with any symptoms in infants.<br><br>METHODS: This was a cross-sectional study of 1019 term deliveries of women participating in the prospective Health and Early Life Microbiota (HELMi) birth cohort study between March 2016 and March 2018 in the capital region of Finland. The data on antibiotic use were collected from the hospital records.<br><br>RESULTS: In total, 37% of the mothers received antibiotics during childbirth and 100% in Caesarean Sects.&#xa0;(17% of the deliveries). Less than 5% of antibiotics were non-prophylactic. In vaginal deliveries, the most common indication (18%) was prophylaxis for Group B Streptococcus. The most frequently used antibiotics were cefuroxime (22%) and benzylpenicillin (15%), and 56% received only one dose. In infants exposed to antibiotics during delivery, defecation frequency was higher during the first months (p-value&#x2009;<&#x2009;0.0001- 0.0145), and weight gain was higher at the age of three months (p-value 0.0371).<br><br>CONCLUSION: More than every third new-born in a developed country is exposed to antibiotics during birth. Our findings support the hypothesis that maternal antibiotics given during birth have an impact on the well-being of the infants. These findings should inform current policies for prophylactic antibiotics in childbirth.}, }
@article {pmid36680587, year = {2023}, author = {Kim, E and Yang, SM and Kim, HY}, title = {Weissella and the two Janus faces of the genus.}, journal = {Applied microbiology and biotechnology}, volume = {107}, number = {4}, pages = {1119-1127}, pmid = {36680587}, issn = {1432-0614}, mesh = {Animals ; Humans ; *Weissella ; *Lactobacillales ; *Probiotics ; *Oncorhynchus mykiss/microbiology ; Fermentation ; }, abstract = {The genus Weissella belongs to the lactic acid bacteria group. It occurs naturally in foods and is a component of the human microbiome. A few Weissella species are candidate probiotics due to their potential for survival under the harsh conditions present in the gastrointestinal tract of humans and animals. Various species have also shown potential for treating and preventing periodontal disease, skin pathologies, and atopic dermatitis; some are used as starters for the fermentation of foods due to their production of exopolysaccharides; and others are used as protective cultures due to their production of weissellicin, a bacteriocin. However, a few Weissella species are opportunistic pathogens, such as W. ceti, which is the etiological agent of weissellosis, a disease in rainbow trout. Additionally, most Weissella species are intrinsically vancomycin-resistant. Thus, the Weissella genus is important from both medical and industrial points of view, and the Janus faces of this genus should be considered in any expected biotechnological applications. In this review, we present an overview of the probiotic potential and pathogenic cases of the Weissella genus reported in the literature.}, }
@article {pmid36679633, year = {2023}, author = {Sánchez-Tirado, E and Agüí, L and González-Cortés, A and Campuzano, S and Yáñez-Sedeño, P and Pingarrón, JM}, title = {Electrochemical (Bio)Sensing Devices for Human-Microbiome-Related Biomarkers.}, journal = {Sensors (Basel, Switzerland)}, volume = {23}, number = {2}, pages = {}, pmid = {36679633}, issn = {1424-8220}, support = {PID2021-122457OB-I00//Spanish Ministerio de Ciencia e Innovaci&#xf3;n/ ; PID2019-103899RB-I00//Spanish Ministerio de Ciencia e Inniovaci&#xf3;n/ ; S2018/NMT-4349//Comunidad de Madrid/ ; }, mesh = {Humans ; Electrochemical Techniques/methods ; Biomarkers ; *Nanostructures ; *Biosensing Techniques/methods ; *Microbiota ; }, abstract = {The study of the human microbiome is a multidisciplinary area ranging from the field of technology to that of personalized medicine. The possibility of using microbiota biomarkers to improve the diagnosis and monitoring of diseases (e.g., cancer), health conditions (e.g., obesity) or relevant processes (e.g., aging) has raised great expectations, also in the field of bioelectroanalytical chemistry. The well-known advantages of electrochemical biosensors-high sensitivity, fast response, and the possibility of miniaturization, together with the potential for new nanomaterials to improve their design and performance-position them as unique tools to provide a better understanding of the entities of the human microbiome and raise the prospect of huge and important developments in the coming years. This review article compiles recent applications of electrochemical (bio)sensors for monitoring microbial metabolites and disease biomarkers related to different types of human microbiome, with a special focus on the gastrointestinal microbiome. Examples of electrochemical devices applied to real samples are critically discussed, as well as challenges to be faced and where future developments are expected to go.}, }
@article {pmid36675926, year = {2023}, author = {Maas, E and Penders, J and Venema, K}, title = {Modelling the Gut Fungal-Community in TIM-2 with a Microbiota from Healthy Individuals.}, journal = {Journal of fungi (Basel, Switzerland)}, volume = {9}, number = {1}, pages = {}, pmid = {36675926}, issn = {2309-608X}, abstract = {Most research on the human microbiome focuses on the bacterial component, and this has led to a lack of information about the fungal component (mycobiota) and how this can influence human health, e.g., by modulation through the diet. The validated, dynamic computer-controlled model of the colon (TIM-2) is an in vitro model to study the microbiome and how this is influenced by interventions such as diet. In this study, it was used to the study the gut fungal-community. This was done in combination with next-generation sequencing of the ITS2 region for fungi and 16S rRNA for bacteria. Different dietary interventions (control diet (SIEM), high-carbohydrate, high-protein, glucose as a carbon source) were performed, to see if diet could shape the mycobiome. The mycobiome was investigated after the adaptation period, and throughout the intervention period which lasted 72 h, and samples were taken every 24 h. The fungal community showed low diversity and a greater variability when compared to bacteria. The mycobiome was affected most in the first hours of the adaptation period. Taxonomic classification showed that at the phylum-level Ascomycota and Basidiomycota dominated, while Agaricus, Aspergillus, Candida, Penicillum, Malassezia, Saccharomyces, Aureobasidium, Mycosphaerella, Mucor and Clavispora were the most abundant genera. During the intervention period, it was shown that the change of diet could influence the diversity. Clustering of samples for different time points was analyzed using Bray−Curtis dissimilarities. Samples of t0 clustered together, and samples of all other time points clustered together. The Bray−Curtis-dissimilarity analysis also showed that for the different dietary interventions, samples treated with glucose clustered together and were different from the other groups (p < 0.05, PERMANOVA). Taxonomic classification showed that the genera Alternaria, Thanatephorus, Candida and Dekkera differentially changed for the various diet groups (p < 0.05, Kruskal−Wallis). These results show that the mycobiota could be modelled in TIM-2; however, the low diversity and high variability make studying fungal, as compared to bacterial, communities, much more challenging. Future research should focus on the optimization of the stability of the fungal community to increase the strength of the results.}, }
@article {pmid36675055, year = {2023}, author = {Kustrimovic, N and Bombelli, R and Baci, D and Mortara, L}, title = {Microbiome and Prostate Cancer: A Novel Target for Prevention and Treatment.}, journal = {International journal of molecular sciences}, volume = {24}, number = {2}, pages = {}, pmid = {36675055}, issn = {1422-0067}, mesh = {Male ; Humans ; *Microbiota/physiology ; *Prostatic Neoplasms/therapy/pathology ; *Gastrointestinal Microbiome/physiology ; Prostate/pathology ; Inflammation ; Dysbiosis ; }, abstract = {Growing evidence of the microbiome's role in human health and disease has emerged since the creation of the Human Microbiome Project. Recent studies suggest that alterations in microbiota composition (dysbiosis) may play an essential role in the occurrence, development, and prognosis of prostate cancer (PCa), which remains the second most frequent male malignancy worldwide. Current advances in biological technologies, such as high-throughput sequencing, transcriptomics, and metabolomics, have enabled research on the gut, urinary, and intra-prostate microbiome signature and the correlation with local and systemic inflammation, host immunity response, and PCa progression. Several microbial species and their metabolites facilitate PCa insurgence through genotoxin-mediated mutagenesis or by driving tumor-promoting inflammation and dysfunctional immunosurveillance. However, the impact of the microbiome on PCa development, progression, and response to treatment is complex and needs to be fully understood. This review addresses the current knowledge on the host-microbe interaction and the risk of PCa, providing novel insights into the intraprostatic, gut, and urinary microbiome mechanisms leading to PCa carcinogenesis and treatment response. In this paper, we provide a detailed overview of diet changes, gut microbiome, and emerging therapeutic approaches related to the microbiome and PCa. Further investigation on the prostate-related microbiome and large-scale clinical trials testing the efficacy of microbiota modulation approaches may improve patient outcomes while fulfilling the literature gap of microbial-immune-cancer-cell mechanistic interactions.}, }
@article {pmid36674563, year = {2023}, author = {He, S and Chakraborty, R and Ranganathan, S}, title = {Metaproteomic Analysis of an Oral Squamous Cell Carcinoma Dataset Suggests Diagnostic Potential of the Mycobiome.}, journal = {International journal of molecular sciences}, volume = {24}, number = {2}, pages = {}, pmid = {36674563}, issn = {1422-0067}, mesh = {Humans ; Squamous Cell Carcinoma of Head and Neck ; *Carcinoma, Squamous Cell/metabolism ; *Mouth Neoplasms/pathology ; *Mycobiome ; Proteomics/methods ; *Head and Neck Neoplasms ; }, abstract = {Oral squamous cell carcinoma (OSCC) is the most common head and neck malignancy, with an estimated 5-year survival rate of only 40-50%, largely due to late detection and diagnosis. Emerging evidence suggests that the human microbiome may be implicated in OSCC, with oral microbiome studies putatively identifying relevant bacterial species. As the impact of other microbial organisms, such as fungi and viruses, has largely been neglected, a bioinformatic approach utilizing the Trans-Proteomic Pipeline (TPP) and the R statistical programming language was implemented here to investigate not only bacteria, but also viruses and fungi in the context of a publicly available, OSCC, mass spectrometry (MS) dataset. Overall viral, bacterial, and fungal composition was inferred in control and OSCC patient tissue from protein data, with a range of proteins observed to be differentially enriched between healthy and OSCC conditions, of which the fungal protein profile presented as the best potential discriminator of OSCC within the analysed dataset. While the current project sheds new light on the fungal and viral spheres of the oral microbiome in cancer in silico, further research will be required to validate these findings in an experimental setting.}, }
@article {pmid36672959, year = {2023}, author = {Park, DJ and Plantinga, AM}, title = {Impact of Data and Study Characteristics on Microbiome Volatility Estimates.}, journal = {Genes}, volume = {14}, number = {1}, pages = {}, pmid = {36672959}, issn = {2073-4425}, mesh = {Female ; Humans ; *Microbiota ; Bacteria/genetics ; Longitudinal Studies ; Time Factors ; Specimen Handling ; }, abstract = {The human microbiome is a dynamic community of bacteria, viruses, fungi, and other microorganisms. Both the composition of the microbiome (the microbes that are present and their relative abundances) and the temporal variability of the microbiome (the magnitude of changes in their composition across time, called volatility) has been associated with human health. However, the effect of unbalanced sampling intervals and differential read depth on the estimates of microbiome volatility has not been thoroughly assessed. Using four publicly available gut and vaginal microbiome time series, we subsampled the datasets to several sampling intervals and read depths and then compared additive, multiplicative, centered log ratio (CLR)-based, qualitative, and distance-based measures of microbiome volatility between the conditions. We find that longer sampling intervals are associated with larger quantitative measures of change (particularly for common taxa), but not with qualitative measures of change or distance-based volatility quantification. A lower sequencing read depth is associated with smaller multiplicative, CLR-based, and qualitative measures of change (particularly for less common taxa). Strategic subsampling may serve as a useful sensitivity analysis in unbalanced longitudinal studies investigating clinical associations with microbiome volatility.}, }
@article {pmid36672595, year = {2022}, author = {Brogna, C and Cristoni, S and Brogna, B and Bisaccia, DR and Marino, G and Viduto, V and Montano, L and Piscopo, M}, title = {Toxin-like Peptides from the Bacterial Cultures Derived from Gut Microbiome Infected by SARS-CoV-2-New Data for a Possible Role in the Long COVID Pattern.}, journal = {Biomedicines}, volume = {11}, number = {1}, pages = {}, pmid = {36672595}, issn = {2227-9059}, abstract = {It has been 3 years since the beginning of the SARS-CoV-2 outbreak, however it is as yet little known how to care for the acute COVID-19 and long COVID patients. COVID-19 clinical manifestations are of both pulmonary and extra-pulmonary types. Extra-pulmonary ones include extreme tiredness (fatigue), shortness of breath, muscle aches, hyposmia, dysgeusia, and other neurological manifestations. In other autoimmune diseases, such as Parkinson's disease (PD) or Alzheimer's Disease (AD), it is well known that role of acetylcholine is crucial in olfactory dysfunction. We have already observed the presence of toxin-like peptides in plasma, urine, and faecal samples from COVID-19 patients, which are very similar to molecules known to alter acetylcholine signaling. After observing the production of these peptides in bacterial cultures, we have performed additional proteomics analyses to better understand their behavior and reported the extended data from our latest in vitro experiment. It seems that the gut microbiome continues to produce toxin-like peptides also after the decrease of RNA SARS-CoV-2 viral load at molecular tests. These toxicological interactions between the gut/human microbiome bacteria and the virus suggest a new scenario in the study of the clinical symptoms in long COVID and also in acute COVID-19 patients. It is discussed that in the bacteriophage similar behavior, the presence of toxins produced by bacteria continuously after viral aggression can be blocked using an appropriate combination of certain drugs.}, }
@article {pmid36662710, year = {2023}, author = {Brenes, LR and Johnson, AD and Lohse, MB}, title = {Farnesol and phosphorylation of the transcriptional regulator Efg1 affect Candida albicans white-opaque switching rates.}, journal = {PloS one}, volume = {18}, number = {1}, pages = {e0280233}, pmid = {36662710}, issn = {1932-6203}, support = {R01 AI049187/AI/NIAID NIH HHS/United States ; }, mesh = {Humans ; *Candida albicans/drug effects/genetics/metabolism ; *Farnesol/pharmacology ; *Fungal Proteins/genetics/metabolism ; Gene Expression Regulation, Fungal ; Genetic Techniques ; Phenotype ; Phosphorylation ; }, abstract = {Candida albicans is a normal member of the human microbiome and an opportunistic fungal pathogen. This species undergoes several morphological transitions, and here we consider white-opaque switching. In this switching program, C. albicans reversibly alternates between two cell types, named "white" and "opaque," each of which is normally stable across thousands of cell divisions. Although switching under most conditions is stochastic and rare, certain environmental signals or genetic manipulations can dramatically increase the rate of switching. Here, we report the identification of two new inputs which affect white-to-opaque switching rates. The first, exposure to sub-micromolar concentrations of (E,E)-farnesol, reduces white-to-opaque switching by ten-fold or more. The second input, an inferred PKA phosphorylation of residue T208 on the transcriptional regulator Efg1, increases white-to-opaque switching ten-fold. Combining these and other environmental inputs results in a variety of different switching rates, indicating that a given rate represents the integration of multiple inputs.}, }
@article {pmid36660365, year = {2023}, author = {Trovão, F and Correia, VG and Lourenço, FM and Ribeiro, DO and Carvalho, AL and Palma, AS and Pinheiro, BA}, title = {The structure of a Bacteroides thetaiotaomicron carbohydrate-binding module provides new insight into the recognition of complex pectic polysaccharides by the human microbiome.}, journal = {Journal of structural biology: X}, volume = {7}, number = {}, pages = {100084}, pmid = {36660365}, issn = {2590-1524}, abstract = {The Bacteroides thetaiotaomicron has developed a consortium of enzymes capable of overcoming steric constraints and degrading, in a sequential manner, the complex rhamnogalacturonan II (RG-II) polysaccharide. BT0996 protein acts in the initial stages of the RG-II depolymerisation, where its two catalytic modules remove the terminal monosaccharides from RG-II side chains A and B. BT0996 is modular and has three putative carbohydrate-binding modules (CBMs) for which the roles in the RG-II degradation are unknown. Here, we present the characterisation of the module at the C-terminal domain, which we designated BT0996-C. The high-resolution structure obtained by X-ray crystallography reveals that the protein displays a typical β-sandwich fold with structural similarity to CBMs assigned to families 6 and 35. The distinctive features are: 1) the presence of several charged residues at the BT0996-C surface creating a large, broad positive lysine-rich patch that encompasses the putative binding site; and 2) the absence of the highly conserved binding-site signatures observed in CBMs from families 6 and 35, such as region A tryptophan and region C asparagine. These findings hint at a binding mode of BT0996-C not yet observed in its homologues. In line with this, carbohydrate microarrays and microscale thermophoresis show the ability of BT0996-C to bind α1-4-linked polygalacturonic acid, and that electrostatic interactions are essential for the recognition of the anionic polysaccharide. The results support the hypothesis that BT0996-C may have evolved to potentiate the action of BT0996 catalytic modules on the complex structure of RG-II by binding to the polygalacturonic acid backbone sequence.}, }
@article {pmid36658342, year = {2023}, author = {Heinken, A and Hertel, J and Acharya, G and Ravcheev, DA and Nyga, M and Okpala, OE and Hogan, M and Magnúsdóttir, S and Martinelli, F and Nap, B and Preciat, G and Edirisinghe, JN and Henry, CS and Fleming, RMT and Thiele, I}, title = {Genome-scale metabolic reconstruction of 7,302 human microorganisms for personalized medicine.}, journal = {Nature biotechnology}, volume = {41}, number = {9}, pages = {1320-1331}, pmid = {36658342}, issn = {1546-1696}, support = {757922/ERC_/European Research Council/International ; RF1 AG058942/AG/NIA NIH HHS/United States ; U19 AG063744/AG/NIA NIH HHS/United States ; }, mesh = {Humans ; Precision Medicine ; Genome ; Genomics ; *Gastrointestinal Microbiome/genetics ; *Microbiota ; }, abstract = {The human microbiome influences the efficacy and safety of a wide variety of commonly prescribed drugs. Designing precision medicine approaches that incorporate microbial metabolism would require strain- and molecule-resolved, scalable computational modeling. Here, we extend our previous resource of genome-scale metabolic reconstructions of human gut microorganisms with a greatly expanded version. AGORA2 (assembly of gut organisms through reconstruction and analysis, version 2) accounts for 7,302 strains, includes strain-resolved drug degradation and biotransformation capabilities for 98 drugs, and was extensively curated based on comparative genomics and literature searches. The microbial reconstructions performed very well against three independently assembled experimental datasets with an accuracy of 0.72 to 0.84, surpassing other reconstruction resources and predicted known microbial drug transformations with an accuracy of 0.81. We demonstrate that AGORA2 enables personalized, strain-resolved modeling by predicting the drug conversion potential of the gut microbiomes from 616 patients with colorectal cancer and controls, which greatly varied between individuals and correlated with age, sex, body mass index and disease stages. AGORA2 serves as a knowledge base for the human microbiome and paves the way to personalized, predictive analysis of host-microbiome metabolic interactions.}, }
@article {pmid36654471, year = {2023}, author = {Shelin, R and Meenakshi, S}, title = {Rise of Bacterial Small Proteins and Peptides in Therapeutic Applications.}, journal = {Protein and peptide letters}, volume = {30}, number = {2}, pages = {126-136}, doi = {10.2174/0929866530666230118144723}, pmid = {36654471}, issn = {1875-5305}, mesh = {*Bacterial Proteins ; *Peptides/therapeutic use/genetics ; Protein Biosynthesis ; Ribosomes ; Amino Acids ; Open Reading Frames ; }, abstract = {BACKGROUND: Polypeptides that comprise less than 100 amino acids (50 amino acids in some cases) are referred to as small proteins (SPs), however, as of date, there is no strict definition. In contrast to the small polypeptides that arise due to proteolytic activity or abrupt protein synthesis, SPs are coded by small open reading frames (sORFs) and are conventionally synthesized by ribosomes.<br><br>PURPOSE OF THE REVIEW: Although proteins that contain more than 100 amino acids have been studied exquisitely, studies on small proteins have been largely ignored, basically due to the unsuccessful detection of these SPs by traditional methodologies/techniques. Serendipitous observation of several small proteins and elucidation of their vital functions in cellular processes opened the floodgate of a new area of research on the new family of proteins called "Small proteins". Having known the significance of such SPs, several advanced techniques are being developed to precisely identify and characterize them.<br><br>CONCLUSION: Bacterial small proteins (BSPs) are being intensely investigated in recent days and that has brought the versatile role of BSPs into the limelight. In particular, identification of the fact that BSPs exhibit antimicrobial activity has further expanded its scope in the area of therapeutics. Since the microbiome plays an inevitable role in determining the outcome of personalized medicine, studies on the secretory small proteins of the microbiome are gaining momentum. This review discusses the importance of bacterial small proteins and peptides in terms of their therapeutic applications.}, }
@article {pmid36653831, year = {2023}, author = {Zyoud, SH and Shakhshir, M and Abushanab, AS and Koni, A and Shahwan, M and Jairoun, AA and Al-Jabi, SW}, title = {Mapping the output of the global literature on the links between gut microbiota and COVID-19.}, journal = {Journal of health, population, and nutrition}, volume = {42}, number = {1}, pages = {3}, pmid = {36653831}, issn = {2072-1315}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *COVID-19 ; *Probiotics/therapeutic use ; Anti-Bacterial Agents ; Databases, Factual ; }, abstract = {BACKGROUND: The term "human microbiota" refers to populations of microorganisms that live harmoniously in co-existence with humans. They contribute significantly to the host's immunological response when confronted with a respiratory viral infection. However, little is known about the relationship between the human microbiome and COVID-19. Therefore, our objective is to perform a bibliometric analysis to explore the overall structure and hotspots of research activity on the links between microbiota and COVID-19 at the global level.<br><br>METHODS: The research literature on the microbiota and COVID-19 published between 2020 and 2022 was obtained from the Scopus database. Bibliometric analysis and network visualization were performed with VOSviewer.<br><br>RESULTS: Of the 701 publications selected, the USA contributed the most (n&#x2009;=&#x2009;157, 22.40%), followed by China (n&#x2009;=&#x2009;118, 16.83%) and Italy (n&#x2009;=&#x2009;82, 11.70%). Hotspots in this field were "COVID-19 is associated with an altered upper respiratory tract microbiome," "the effect of antibiotics on the gut microbiome," as well as "patient nutrition and probiotic therapy in COVID-19."<br><br>CONCLUSIONS: The links between microbiota and COVID-19 remain an urgent concern at present, and the use of probiotics or/and antibiotics during the pandemic needs to be further improved. This landscape analysis of the links between the microbiota and COVID-19 will provide a basis for future research.}, }
@article {pmid36653448, year = {2023}, author = {Valles-Colomer, M and Blanco-Míguez, A and Manghi, P and Asnicar, F and Dubois, L and Golzato, D and Armanini, F and Cumbo, F and Huang, KD and Manara, S and Masetti, G and Pinto, F and Piperni, E and Punčochář, M and Ricci, L and Zolfo, M and Farrant, O and Goncalves, A and Selma-Royo, M and Binetti, AG and Becerra, JE and Han, B and Lusingu, J and Amuasi, J and Amoroso, L and Visconti, A and Steves, CM and Falchi, M and Filosi, M and Tett, A and Last, A and Xu, Q and Qin, N and Qin, H and May, J and Eibach, D and Corrias, MV and Ponzoni, M and Pasolli, E and Spector, TD and Domenici, E and Collado, MC and Segata, N}, title = {The person-to-person transmission landscape of the gut and oral microbiomes.}, journal = {Nature}, volume = {614}, number = {7946}, pages = {125-135}, pmid = {36653448}, issn = {1476-4687}, support = {MR/N01183X/1/MRC_/Medical Research Council/United Kingdom ; MR/S005013/1/MRC_/Medical Research Council/United Kingdom ; R01 CA230551/CA/NCI NIH HHS/United States ; U01 CA230551/CA/NCI NIH HHS/United States ; }, mesh = {Female ; Humans ; Infant ; *Bacteria/classification/genetics/isolation &amp; purification ; *Gastrointestinal Microbiome/genetics ; Metagenome ; *Microbiota/genetics ; Mothers ; *Mouth/microbiology ; Infectious Disease Transmission, Vertical ; Family Characteristics ; Aging ; *Disease Transmission, Infectious ; Time Factors ; Microbial Viability ; *Home Environment ; }, abstract = {The human microbiome is an integral component of the human body and a co-determinant of several health conditions[1,2]. However, the extent to which interpersonal relations shape the individual genetic makeup of the microbiome and its transmission within and across populations remains largely unknown[3,4]. Here, capitalizing on more than 9,700 human metagenomes and computational strain-level profiling, we detected extensive bacterial strain sharing across individuals (more than 10 million instances) with distinct mother-to-infant, intra-household and intra-population transmission patterns. Mother-to-infant gut microbiome transmission was considerable and stable during infancy (around 50% of the same strains among shared species (strain-sharing rate)) and remained detectable at older ages. By contrast, the transmission of the oral microbiome occurred largely horizontally and was enhanced by the duration of cohabitation. There was substantial strain sharing among cohabiting individuals, with 12% and 32% median strain-sharing rates for the gut and oral microbiomes, and time since cohabitation affected strain sharing more than age or genetics did. Bacterial strain sharing additionally recapitulated host population structures better than species-level profiles did. Finally, distinct taxa appeared as efficient spreaders across transmission modes and were associated with different predicted bacterial phenotypes linked with out-of-host survival capabilities. The extent of microorganism transmission that we describe underscores its relevance in human microbiome studies[5], especially those on non-infectious, microbiome-associated diseases.}, }
@article {pmid36647645, year = {2023}, author = {Liu, ZH and Zhou, XD and Zhang, LL}, title = {[Research Progress in the Correlation Between Oral Microbiota and Chronic Kidney Disease].}, journal = {Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition}, volume = {54}, number = {1}, pages = {66-70}, pmid = {36647645}, issn = {1672-173X}, mesh = {Humans ; Dysbiosis/complications ; Quality of Life ; *Gastrointestinal Microbiome ; *Renal Insufficiency, Chronic/complications ; *Microbiota ; }, abstract = {Chronic kidney disease (CKD), one of the common clinical urological diseases, is increasingly more prevalent in recent years and has emerged as a major concern of public health around the globe. The continuous recurrence of CKD caused by renal function impairment leads eventually to irreversible renal failure and severe systemic complications, which causes severe negative impact on the quality of life of the patient. As an essential component of human microbiome, oral microbiota plays a major role in maintaining health, and there has been research suggesting close association between oral dysbiosis and CKD. It is therefore of great clinical significance to understand the correlation between CKD and oral microbiota. Herein, we reviewed the characteristics of oral microbiota of CKD patients, the possible mechanisms of oral microbiota's involvement in the pathogenesis and development of CKD, and the latest research findings on oral dysbiosis and CKD, with a view to finding new approaches to early prevention and control of CKD through oral microbial targets.}, }
@article {pmid36647641, year = {2023}, author = {Guan, ZW and Xu, TQ and Shen, S and Li, X and Feng, Q}, title = {[Pathways and Mechanisms of Periodontitis Contributing to Adverse Pregnancy Outcomes].}, journal = {Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition}, volume = {54}, number = {1}, pages = {39-48}, pmid = {36647641}, issn = {1672-173X}, mesh = {Animals ; Pregnancy ; Female ; Humans ; Pregnancy Outcome ; Placenta ; *Periodontitis/complications/microbiology ; *Pregnancy Complications ; Risk Factors ; }, abstract = {Periodontitis is a chronic oral inflammatory disease with a high incidence in the global population. Periodontal pathogens can colonize and infect multiple human tissues and organs through blood transmission, which is an important risk factor of many systemic diseases. Recently, the correlation between periodontitis and adverse pregnancy outcomes (APOs) has attracted growing research interest. Herein, we systematically reviewed the research progress in the relationship between periodontitis and APOs and summarized reported findings on the pathways and mechanisms by which periodontitis contributes to APOs. We also clarified that intrauterine infection caused by oral pathogens transmitted through blood is an important pathway by which periodontitis interferes with pregnancy. In addition, further research focused on the discovery of more APOs-related oral pathogenic bacteria and their virulence factors, analysis of the interaction between pathogenic bacteria and placental tissue, and pathogenic pathways of oral bacterial invasion of the fetus will promote thorough analysis of the specific molecular mechanism of how periodontitis affects APOs. Furthermore, the validation of the results of human population-based studies through animal/cell experiments and the translation into effective intervention strategies are of great clinical significance to the prevention and control of the occurrence and development of APOs.}, }
@article {pmid36647379, year = {2023}, author = {Mochochoko, BM and Pohl, CH and O'Neill, HG}, title = {Candida albicans-enteric viral interactions-The prostaglandin E2 connection and host immune responses.}, journal = {iScience}, volume = {26}, number = {1}, pages = {105870}, pmid = {36647379}, issn = {2589-0042}, abstract = {The human microbiome comprises trillions of microorganisms residing within different mucosal cavities and across the body surface. The gut microbiota modulates host susceptibility to viral infections in several ways, and microbial interkingdom interactions increase viral infectivity within the gut. Candida albicans, a frequently encountered fungal species in the gut, produces highly structured biofilms and eicosanoids such as prostaglandin E2 (PGE2), which aid in viral protection and replication. These biofilms encompass viruses and provide a shield from antiviral drugs or the immune system. PGE2 is a key modulator of active inflammation with the potential to regulate interferon signaling upon microbial invasion or viral infections. In this review, we raise the perspective of gut interkingdom interactions involving C. albicans and enteric viruses, with a special focus on biofilms, PGE2, and viral replication. Ultimately, we discuss the possible implications of C. albicans-enteric virus associations on host immune responses, particularly the interferon signaling pathway.}, }
@article {pmid36646294, year = {2023}, author = {Boopathi, S and Kumar, RMS and Priya, PS and Haridevamuthu, B and Nayak, SPRR and Chulenbayeva, L and Almagul, K and Arockiaraj, J}, title = {Gut Enterobacteriaceae and uraemic toxins - Perpetrators for ageing.}, journal = {Experimental gerontology}, volume = {173}, number = {}, pages = {112088}, doi = {10.1016/j.exger.2023.112088}, pmid = {36646294}, issn = {1873-6815}, mesh = {Aged, 80 and over ; Humans ; Aged ; *Enterobacteriaceae ; *Uremic Toxins ; Aging/physiology ; Longevity/physiology ; Liver ; }, abstract = {Ageing is a complex process that is associated with changes in the composition and functions of gut microbiota. Reduction of gut commensals is the hallmarks of ageing, which favours the expansion of pathogens even in healthy centenarians. Interestingly, gut Enterobacteriaceae have been found to be increased with age and also consistently observed in the patients with metabolic diseases. Thus, they are associated with all-cause mortality, regardless of genetic origin, lifestyle, and fatality rate. Moreover, Enterobacteriaceae are also implicated in accelerating the ageing process through telomere attrition, cellular senescence, inflammasome activation and impairing the functions of mitochondria. However, acceleration of ageing is likely to be determined by intrinsic interactions between Enterobacteriaceae and other associated gut bacteria. Several studies suggested that Enterobacteriaceae possess genes for the synthesis of uraemic toxins. In addition to intestine, Enterobacteriaceae and their toxic metabolites have also been found in other organs, such as adipose tissue and liver and that are implicated in multiorgan dysfunction and age-related diseases. Therefore, targeting Enterobacteriaceae is a nuance approach for reducing inflammaging and enhancing the longevity of older people. This review is intended to highlight the current knowledge of Enterobacteriaceae-mediated acceleration of ageing process.}, }
@article {pmid36645293, year = {2023}, author = {Huang, X and Erickson, DL and Meng, J}, title = {PhyloPlus: a Universal Tool for Phylogenetic Interrogation of Metagenomic Communities.}, journal = {mBio}, volume = {14}, number = {1}, pages = {e0345522}, pmid = {36645293}, issn = {2150-7511}, support = {U01 FD001418/FD/FDA HHS/United States ; }, mesh = {Humans ; Phylogeny ; *Metagenome ; Metagenomics ; *Microbiota/genetics ; Bacteria/genetics ; RNA, Ribosomal, 16S/genetics ; }, abstract = {Phylogeny is a powerful tool that can be incorporated into quantitative descriptions of community diversity, yet its use has been limited largely due to the difficulty in constructing phylogenies which incorporate the wide genomic diversity of microbial communities. Here, we describe the development of a web portal, PhyloPlus, which enables users to generate customized phylogenies that may be applied to any bacterial or archaeal communities. We demonstrate the power of phylogeny by comparing metrics that employ phylogeny with those that do not when applied to data sets from two metagenomic studies (fermented food, n = 58; human microbiome, n = 60). This example shows how inclusion of all bacterial species identified by taxonomic classifiers (Kraken2 and Kaiju) made the phylogeny perfectly congruent to the corresponding classification outputs. Our phylogeny-based approach also enabled the construction of more constrained null models which (i) shed light into community structure and (ii) minimize potential inflation of type I errors. Construction of such null models allowed for the observation of under-dispersion in 44 (75.86%) food samples, with the metacommunity defined as bacteria that were found in different food matrices. We also observed that closely related species with high abundance and uneven distribution across different sites could potentially exaggerate the dissimilarity between phylogenetically similar communities if they were measured using traditional species-based metrics (Padj. = 0.003), whereas this effect was mitigated by incorporating phylogeny (Padj. = 1). In summary, our tool can provide additional insights into microbial communities of interest and facilitate the use of phylogeny-based approaches in metagenomic analyses. IMPORTANCE There has been an explosion of interest in how microbial diversity affects human health, food safety, and environmental functions among many other processes. Accurately measuring the diversity and structure of those communities is central to understanding their effects. Here, we describe the development of a freely available online tool, PhyloPlus, which allows users to generate custom phylogenies that may be applied to any data set, thereby removing a major obstacle to the application of phylogeny to metagenomic data analysis. We demonstrate that the genetic relatedness of the organisms within those communities is a critical feature of their overall diversity, and that using a phylogeny which captures and quantifies this diversity allows for much more accurate descriptions while preventing misleading conclusions based on estimates that ignore evolutionary relationships.}, }
@article {pmid36644130, year = {2023}, author = {Lo Presti, A and Del Chierico, F and Altomare, A and Zorzi, F and Monteleone, G and Putignani, L and Angeletti, S and Cicala, M and Guarino, MPL and Ciccozzi, M}, title = {Phylogenetic analysis of Prevotella copri from fecal and mucosal microbiota of IBS and IBD patients.}, journal = {Therapeutic advances in gastroenterology}, volume = {16}, number = {}, pages = {17562848221136328}, pmid = {36644130}, issn = {1756-283X}, abstract = {BACKGROUND: Prevotella copri is the most abundant member of the genus Prevotella that inhabits the human large intestines. Evidences correlated the increase in Prevotella abundance to inflammatory disorders, suggesting a pathobiont role.<br><br>OBJECTIVES: The aim of this study was to investigate the phylogenetic dynamics of P. copri in patients with irritable bowel syndrome (IBS), inflammatory bowel diseases (IBDs) and in healthy volunteers (CTRL).<br><br>DESIGN: A phylogenetic approach was used to characterize 64 P. copri 16S rRNA sequences, selected from a metagenomic database of fecal and mucosal samples from 52 patients affected by IBD, 44 by IBS and 59 healthy.<br><br>METHODS: Phylogenetic reconstructions were carried out using the maximum likelihood (ML) and Bayesian methods.<br><br>RESULTS: Maximum likelihood phylogenetic tree applied onto reference and data sets, assigned all the reads to P. copri clade, in agreement with the taxonomic classification previously obtained. The longer mean genetic distances were observed for both the couples IBD and CTRL and IBD and IBS, respect to the distance between IBS and CTRL, for fecal samples. The intra-group mean genetic distance increased going from IBS to CTRLs to IBD, indicating elevated genetic variability within IBD of P. copri sequences. None clustering based on the tissue inflammation or on the disease status was evidenced, leading to infer that the variability seemed to not be influenced by concomitant diseases, disease phenotypes or tissue inflammation. Moreover, patients with IBS appeared colonized by different strains of P. copri. In IBS, a correlation between isolates and disease grading was observed.<br><br>CONCLUSION: The characterization of P. copri phylogeny is relevant to better understand the interactions between microbiota and pathophysiology of IBD and IBS, especially for future development of therapies based on microbes (e.g. probiotics and synbiotics), to restore the microbiota in these bowel diseases.}, }
@article {pmid36629257, year = {2023}, author = {Pellegrino, GM and Browne, TS and Sharath, K and Bari, KA and Vancuren, SJ and Allen-Vercoe, E and Gloor, GB and Edgell, DR}, title = {Metabolically-targeted dCas9 expression in bacteria.}, journal = {Nucleic acids research}, volume = {51}, number = {2}, pages = {982-996}, pmid = {36629257}, issn = {1362-4962}, mesh = {Humans ; *Bacteria/genetics ; CRISPR-Cas Systems ; Escherichia coli/genetics ; Gene Expression Regulation ; *Glucuronides/metabolism ; Transcription Factors/genetics ; *CRISPR-Associated Protein 9/genetics ; *Operon ; }, abstract = {The ability to restrict gene expression to a relevant bacterial species in a complex microbiome is an unsolved problem. In the context of the human microbiome, one desirable target metabolic activity are glucuronide-utilization enzymes (GUS) that are implicated in the toxic re-activation of glucuronidated compounds in the human gastrointestinal (GI) tract, including the chemotherapeutic drug irinotecan. Here, we take advantage of the variable distribution of GUS enzymes in bacteria as a means to distinguish between bacteria with GUS activity, and re-purpose the glucuronide-responsive GusR transcription factor as a biosensor to regulate dCas9 expression in response to glucuronide inducers. We fused the Escherichia coli gusA regulatory region to the dCas9 gene to create pGreg-dCas9, and showed that dCas9 expression is induced by glucuronides, but not other carbon sources. When conjugated from E. coli to Gammaproteobacteria derived from human stool, dCas9 expression from pGreg-dCas9 was restricted to GUS-positive bacteria. dCas9-sgRNAs targeted to gusA specifically down-regulated gus operon transcription in Gammaproteobacteria, with a resulting ∼100-fold decrease in GusA activity. Our data outline a general strategy to re-purpose bacterial transcription factors responsive to exogenous metabolites for precise ligand-dependent expression of genetic tools such as dCas9 in diverse bacterial species.}, }
@article {pmid36625592, year = {2023}, author = {Swayambhu, M and Kümmerli, R and Arora, N}, title = {Microbiome-Based Stain Analyses in Crime Scenes.}, journal = {Applied and environmental microbiology}, volume = {89}, number = {1}, pages = {e0132522}, pmid = {36625592}, issn = {1098-5336}, mesh = {*Forensic Sciences/methods ; Machine Learning ; Crime ; *Microbiota ; High-Throughput Nucleotide Sequencing ; }, abstract = {Recent advances in next-generation sequencing technologies (NGS) coupled with machine learning have demonstrated the potential of microbiome-based analyses in applied areas such as clinical diagnostics and forensic sciences. Particularly in forensics, microbial markers in biological stains left at a crime scene can provide valuable information for the reconstruction of crime scene cases, as they contain information on bodily origin, the time since deposition, and donor(s) of the stain. Importantly, microbiome-based analyses provide a complementary or an alternative approach to current methods when these are limited or not feasible. Despite the promising results from recent research, microbiome-based stain analyses are not yet employed in routine casework. In this review, we highlight the two main gaps that need to be addressed before we can successfully integrate microbiome-based analyses in applied areas with a special focus on forensic casework: one is a comprehensive assessment of the method's strengths and limitations, and the other is the establishment of a standard operating procedure. For the latter, we provide a roadmap highlighting key decision steps and offering laboratory and bioinformatic workflow recommendations, while also delineating those aspects that require further testing. Our goal is to ultimately facilitate the streamlining of microbiome-based analyses within the existing forensic framework to provide alternate lines of evidence, thereby improving the quality of investigations.}, }
@article {pmid36624837, year = {2023}, author = {Fumagalli, MR and Saro, SM and Tajana, M and Zapperi, S and La Porta, CAM}, title = {Quantitative analysis of disease-related metabolic dysregulation of human microbiota.}, journal = {iScience}, volume = {26}, number = {1}, pages = {105868}, pmid = {36624837}, issn = {2589-0042}, abstract = {The metabolic activity of all the micro-organism composing the human microbiome interacts with the host metabolism contributing to human health and disease in a way that is not fully understood. Here, we introduce STELLA, a computational method to derive the spectrum of metabolites associated with the microbiome of an individual. STELLA integrates known information on metabolic pathways associated with each bacterial species and extracts from these the list of metabolic products of each singular reaction by means of automatic text analysis. By comparing the result obtained on a single subject with the metabolic profile data of a control set of healthy subjects, we are able to identify individual metabolic alterations. To illustrate the method, we present applications to autism spectrum disorder and multiple sclerosis.}, }
@article {pmid36624275, year = {2023}, author = {Tonelli, A and Lumngwena, EN and Ntusi, NAB}, title = {The oral microbiome in the pathophysiology of cardiovascular disease.}, journal = {Nature reviews. Cardiology}, volume = {20}, number = {6}, pages = {386-403}, pmid = {36624275}, issn = {1759-5010}, mesh = {Animals ; Humans ; *Cardiovascular Diseases/prevention &amp; control ; Dysbiosis/complications ; *Microbiota ; *Gastrointestinal Microbiome ; *Heart Failure/complications ; }, abstract = {Despite advances in our understanding of the pathophysiology of many cardiovascular diseases (CVDs) and expansion of available therapies, the global burden of CVD-associated morbidity and mortality remains unacceptably high. Important gaps remain in our understanding of the mechanisms of CVD and determinants of disease progression. In the past decade, much research has been conducted on the human microbiome and its potential role in modulating CVD. With the advent of high-throughput technologies and multiomics analyses, the complex and dynamic relationship between the microbiota, their 'theatre of activity' and the host is gradually being elucidated. The relationship between the gut microbiome and CVD is well established. Much less is known about the role of disruption (dysbiosis) of the oral microbiome; however, interest in the field is growing, as is the body of literature from basic science and animal and human investigations. In this Review, we examine the link between the oral microbiome and CVD, specifically coronary artery disease, stroke, peripheral artery disease, heart failure, infective endocarditis and rheumatic heart disease. We discuss the various mechanisms by which oral dysbiosis contributes to CVD pathogenesis and potential strategies for prevention and treatment.}, }
@article {pmid36620050, year = {2022}, author = {Chmiel, JA and Carr, C and Stuivenberg, GA and Venema, R and Chanyi, RM and Al, KF and Giguere, D and Say, H and Akouris, PP and Domínguez Romero, SA and Kwong, A and Tai, V and Koval, SF and Razvi, H and Bjazevic, J and Burton, JP}, title = {New perspectives on an old grouping: The genomic and phenotypic variability of Oxalobacter formigenes and the implications for calcium oxalate stone prevention.}, journal = {Frontiers in microbiology}, volume = {13}, number = {}, pages = {1011102}, pmid = {36620050}, issn = {1664-302X}, abstract = {Oxalobacter formigenes is a unique bacterium with the ability to metabolize oxalate as a primary carbon source. Most kidney stones in humans are composed of calcium and oxalate. Therefore, supplementation with an oxalate-degrading bacterium may reduce stone burden in patients suffering from recurrent calcium oxalate-based urolithiasis. Strains of O. formigenes are divided into two groups: group I and group II. However, the differences between strains from each group remain unclear and elucidating these distinctions will provide a better understanding of their physiology and potential clinical applications. Here, genomes from multiple O. formigenes strains underwent whole genome sequencing followed by phylogenetic and functional analyses. Genetic differences suggest that the O. formigenes taxon should be divided into an additional three species: Oxalobacter aliiformigenes sp. nov, Oxalobacter paeniformigenes sp. nov, and Oxalobacter paraformigenes sp. nov. Despite the similarities in the oxalyl-CoA gene (oxc), which is essential for oxalate degradation, these strains have multiple unique genetic features that may be potential exploited for clinical use. Further investigation into the growth of these strains in a simulated fecal environment revealed that O. aliiformigenes strains are capable of thriving within the human gut microbiota. O. aliiformigenes may be a better therapeutic candidate than current group I strains (retaining the name O. formigenes), which have been previously tested and shown to be ineffective as an oral supplement to mitigate stone disease. By performing genomic analyses and identifying these novel characteristics, Oxalobacter strains better suited to mitigation of calcium oxalate-based urolithiasis may be identified in the future.}, }
@article {pmid36613488, year = {2022}, author = {Rodríguez-Daza, MC and de Vos, WM}, title = {Polyphenols as Drivers of a Homeostatic Gut Microecology and Immuno-Metabolic Traits of Akkermansia muciniphila: From Mouse to Man.}, journal = {International journal of molecular sciences}, volume = {24}, number = {1}, pages = {}, pmid = {36613488}, issn = {1422-0067}, support = {024.002.002//SIAM Gravitation/ ; }, mesh = {*Polyphenols/pharmacology/metabolism ; Anthocyanins/metabolism ; Verrucomicrobia/metabolism ; Humans ; *Diabetes Mellitus, Type 2 ; Akkermansia ; }, abstract = {Akkermansia muciniphila is a mucosal symbiont considered a gut microbial marker in healthy individuals, as its relative abundance is significantly reduced in subjects with gut inflammation and metabolic disturbances. Dietary polyphenols can distinctly stimulate the relative abundance of A. muciniphila, contributing to the attenuation of several diseases, including obesity, type 2 diabetes, inflammatory bowel diseases, and liver damage. However, mechanistic insight into how polyphenols stimulate A. muciniphila or its activity is limited. This review focuses on dietary interventions in rodents and humans and in vitro studies using different phenolic classes. We provide critical insights with respect to potential mechanisms explaining the effects of polyphenols affecting A. muciniphila. Anthocyanins, flavan-3-ols, flavonols, flavanones, stilbenes, and phenolic acids are shown to increase relative A. muciniphila levels in vivo, whereas lignans exert the opposite effect. Clinical trials show consistent findings, and high intervariability relying on the gut microbiota composition at the baseline and the presence of multiple polyphenol degraders appear to be cardinal determinants in inducing A. muciniphila and associated benefits by polyphenol intake. Polyphenols signal to the AhR receptor and impact the relative abundance of A. muciniphila in a direct and indirect fashion, resulting in the restoration of intestinal epithelial integrity and homeostatic crosstalk with the gut microbiota by affecting IL-22 production. Moreover, recent evidence suggests that A. muciniphila participates in the initial hydrolysis of some polyphenols but does not participate in their complete metabolism. In conclusion, the consumption of polyphenol-rich foods targeting A. muciniphila as a pivotal intermediary represents a promising precision nutritional therapy to prevent and attenuate metabolic and inflammatory diseases.}, }
@article {pmid36612415, year = {2022}, author = {Eggers, S and Bixby, M and Renzetti, S and Curtin, P and Gennings, C}, title = {Human Microbiome Mixture Analysis Using Weighted Quantile Sum Regression.}, journal = {International journal of environmental research and public health}, volume = {20}, number = {1}, pages = {}, pmid = {36612415}, issn = {1660-4601}, support = {U2C ES026555/ES/NIEHS NIH HHS/United States ; K99 ES032884/ES/NIEHS NIH HHS/United States ; P30 ES023515/ES/NIEHS NIH HHS/United States ; T32 HD049311/HD/NICHD NIH HHS/United States ; U2CES026555/ES/NIEHS NIH HHS/United States ; P30ES023515/ES/NIEHS NIH HHS/United States ; }, mesh = {Humans ; Feces ; *Microbiota ; *Gastrointestinal Microbiome ; Obesity ; Body Mass Index ; }, abstract = {Studies of the health effects of the microbiome often measure overall associations by using diversity metrics, and individual taxa associations in separate analyses, but do not consider the correlated relationships between taxa in the microbiome. In this study, we applied random subset weighted quantile sum regression with repeated holdouts (WQSRSRH), a mixture method successfully applied to 'omic data to account for relationships between many predictors, to processed amplicon sequencing data from the Human Microbiome Project. We simulated a binary variable associated with 20 operational taxonomic units (OTUs). WQSRSRH was used to test for the association between the microbiome and the simulated variable, adjusted for sex, and sensitivity and specificity were calculated. The WQSRSRH method was also compared to other standard methods for microbiome analysis. The method was further illustrated using real data from the Growth and Obesity Cohort in Chile to assess the association between the gut microbiome and body mass index. In the analysis with simulated data, WQSRSRH predicted the correct directionality of association between the microbiome and the simulated variable, with an average sensitivity and specificity of 75% and 70%, respectively, in identifying the 20 associated OTUs. WQSRSRH performed better than all other comparison methods. In the illustration analysis of the gut microbiome and obesity, the WQSRSRH analysis identified an inverse association between body mass index and the gut microbe mixture, identifying Bacteroides, Clostridium, Prevotella, and Ruminococcus as important genera in the negative association. The application of WQSRSRH to the microbiome allows for analysis of the mixture effect of all the taxa in the microbiome, while simultaneously identifying the most important to the mixture, and allowing for covariate adjustment. It outperformed other methods when using simulated data, and in analysis with real data found results consistent with other study findings.}, }
@article {pmid36609878, year = {2023}, author = {Grami, E and Badawy, S and Kiljunen, S and Saidi, N and Skurnik, M}, title = {Characterization and genome analysis of Escherichia phage fBC-Eco01, isolated from wastewater in Tunisia.}, journal = {Archives of virology}, volume = {168}, number = {2}, pages = {44}, pmid = {36609878}, issn = {1432-8798}, support = {LR15CERTE04//Tunisian Ministry of Higher Education and Scientific Research/ ; Decision 2016//Jane ja Aatos Erkon S&#xe4;&#xe4;ti&#xf6;/ ; }, mesh = {Wastewater ; Tunisia ; Genome, Viral ; *Bacteriophages/genetics ; Escherichia coli/genetics ; *Siphoviridae/genetics ; }, abstract = {The rise of antibiotic resistance in bacterial strains has led to vigorous exploration for alternative treatments. To this end, phage therapy has been revisited, and it is gaining increasing attention, as it may represent an efficient alternative for treating multiresistant pathogenic bacteria. Phage therapy is considered safe, and phages do not infect eukaryotic cells. There have been many studies investigating phage-host bacteria interactions and the ability of phages to target specific hosts. Escherichia coli is the causative agent of a multitude of infections, ranging from urinary tract infections to sepsis, with growing antibiotic resistance. In this study, we characterized the Escherichia phage fBC-Eco01, which was isolated from a water sample collected at Oued, Tunis. Electron microscopy showed that fBC-Eco01 phage particles have siphovirus morphology, with an icosahedral head of 61 ± 3 nm in diameter and a non-contractile tail of 94 ± 2 nm in length and 12 ± 0.9 nm in width. The genome of fBC-Eco01 is a linear double-stranded DNA of 43.466 bp with a GC content of 50.4%. Comparison to databases allowed annotation of the functions to 39 of the 78 predicted gene products. A single-step growth curve revealed that fBC-Eco01 has a latent period of 30 minutes and a burst size of 175 plaque-forming units (PFU) per infected cell. Genomic analysis indicated that fBC-Eco01 is a member of the subfamily Guernseyvirinae. It is most closely related to a group of phages of the genus Kagunavirus that infect Enterobacter, Raoultella, and Escherichia strains.}, }
@article {pmid36602383, year = {2023}, author = {Swaney, MH and Nelsen, A and Sandstrom, S and Kalan, LR}, title = {Sweat and Sebum Preferences of the Human Skin Microbiota.}, journal = {Microbiology spectrum}, volume = {11}, number = {1}, pages = {e0418022}, pmid = {36602383}, issn = {2165-0497}, support = {F31 AR079846/AR/NIAMS NIH HHS/United States ; R35 GM137828/GM/NIGMS NIH HHS/United States ; T32 AI055397/AI/NIAID NIH HHS/United States ; U19 AI142720/AI/NIAID NIH HHS/United States ; }, mesh = {Humans ; *Sweat/chemistry ; Sebum ; Skin/microbiology ; *Microbiota ; Bacteria/genetics ; }, abstract = {The microorganisms inhabiting human skin must overcome numerous challenges that typically impede microbial growth, including low pH, osmotic pressure, and low nutrient availability. Yet the skin microbiota thrive on the skin and have adapted to these stressful conditions. The limited nutrients available for microbial use in this unique niche include those from host-derived sweat, sebum, and corneocytes. Here, we have developed physiologically relevant, synthetic skin-like growth media composed of compounds present in sweat and sebum. We find that skin-associated bacterial species exhibit unique growth profiles at different concentrations of artificial sweat and sebum. Most strains evaluated demonstrate a preference for high sweat concentrations, while the sebum preference is highly variable, suggesting that the capacity for sebum utilization may be a driver of the skin microbial community structure. In particular, the prominent skin commensal Staphylococcus epidermidis exhibits the strongest preference for sweat while growing equally well across sebum concentrations. Conversely, the growth of Corynebacterium kefirresidentii, another dominant skin microbiome member, is dependent on increasing concentrations of both sweat and sebum but only when sebum is available, suggesting a lipid requirement of this species. Furthermore, we observe that strains with similar growth profiles in the artificial media cluster by phylum, suggesting that phylogeny is a key factor in sweat and sebum use. Importantly, these findings provide an experimental rationale for why different skin microenvironments harbor distinct microbiome communities. In all, our study further emphasizes the importance of studying microorganisms in an ecologically relevant context, which is critical for our understanding of their physiology, ecology, and function on the skin. IMPORTANCE The human skin microbiome is adapted to survive and thrive in the harsh environment of the skin, which is low in nutrient availability. To study skin microorganisms in a system that mimics the natural skin environment, we developed and tested a physiologically relevant, synthetic skin-like growth medium that is composed of compounds found in the human skin secretions sweat and sebum. We find that most skin-associated bacterial species tested prefer high concentrations of artificial sweat but that artificial sebum concentration preference varies from species to species, suggesting that sebum utilization may be an important contributor to skin microbiome composition. This study demonstrates the utility of a skin-like growth medium, which can be applied to diverse microbiological systems, and underscores the importance of studying microorganisms in an ecologically relevant context.}, }
@article {pmid36596832, year = {2023}, author = {Kim, JH and Jeon, JY and Im, YJ and Ha, N and Kim, JK and Moon, SJ and Kim, MG}, title = {Long-term taxonomic and functional stability of the gut microbiome from human fecal samples.}, journal = {Scientific reports}, volume = {13}, number = {1}, pages = {114}, pmid = {36596832}, issn = {2045-2322}, mesh = {Humans ; *Gastrointestinal Microbiome/genetics ; RNA, Ribosomal, 16S/genetics ; Specimen Handling/methods ; Feces ; *Microbiota ; }, abstract = {Appropriate storage of fecal samples is a critical step for unbiased analysis in human microbiome studies. The purpose of this study was to evaluate the stability of the fecal microbial community for up to 18 months. Ten healthy volunteers provided fecal samples at the Jeonbuk National University Hospital. Stool samples were stored under the following six conditions: four different storage temperatures (- 70 °C, - 20 °C, 4 °C, and room temperature [20-25 °C]) and two different collection tubes (OMNIgene-Gut and DNA/RNA shield-fecal collection tubes). The gut microbiome was analyzed with 16S rRNA sequencing. We compared the taxonomic composition, alpha diversity, beta diversity and inferred pathway abundance between the baseline and 18 months after storage. Samples collected in the DNA/RNA Shield-fecal collection tubes showed the best performance in preservation of the taxonomic composition at 18 months. Pairwise differences in alpha diversity metrics showed the least deviation from zero. The PERMANOVA test showed non-significant change of beta diversity metrics (Unweighted Unifrac: q-value 0.268; Weighted Unifrac: q-value 0.848). The functional stability was significantly well preserved in the DNA/RNA Shield-fecal collection tubes (adjusted p value < 0.05). Our results demonstrate the use of the DNA/RNA Shield-fecal collection tube as an alternative storage method for fecal samples to preserve the taxonomic and functional stability of the microbiome over a long term.}, }
@article {pmid36585105, year = {2023}, author = {Chen, BY and Lin, WZ and Li, YL and Bi, C and Du, LJ and Liu, Y and Zhou, LJ and Liu, T and Xu, S and Shi, CJ and Zhu, H and Wang, YL and Sun, JY and Liu, Y and Zhang, WC and Lu, HX and Wang, YH and Feng, Q and Chen, FX and Wang, CQ and Tonetti, MS and Zhu, YQ and Zhang, H and Duan, SZ}, title = {Roles of oral microbiota and oral-gut microbial transmission in hypertension.}, journal = {Journal of advanced research}, volume = {43}, number = {}, pages = {147-161}, pmid = {36585105}, issn = {2090-1224}, mesh = {Humans ; Animals ; Mice ; *Gastrointestinal Microbiome/physiology ; RNA, Ribosomal, 16S/genetics ; Cross-Sectional Studies ; Follow-Up Studies ; Mice, Inbred C57BL ; *Microbiota ; *Hypertension ; *Periodontitis ; }, abstract = {INTRODUCTION: Considerable evidence has linked periodontitis (PD) to hypertension (HTN), but the nature behind this connection is unclear. Dysbiosis of oral microbiota leading to PD is known to aggravate different systematic diseases, but the alteration of oral microbiota in HTN and their impacts on blood pressure (BP) remains to be discovered.<br><br>OBJECTIVES: To characterize the alterations of oral and gut microbiota and their roles in HTN.<br><br>METHODS: We performed a cross-sectional (95 HTN participants and 39 controls) and a 6-month follow-up study (52 HTN participants and 26 controls) to analyze the roles of oral and gut microbiota in HTN. Saliva, subgingival plaques, and feces were collected for 16S rRNA gene sequencing or metagenomic analysis. C57BL/6J mice were pretreated with antibiotics to deplete gut microbiota, and then transplanted with human saliva by gavage to test the impacts of abnormal oral-gut microbial transmission on HTN.<br><br>RESULTS: BP in participants with PD was higher than no PD in both cross-sectional and follow-up cohort. Relative abundances of 14 salivary genera, 15 subgingival genera and 10 gut genera significantly altered in HTN and those of 7 salivary genera, 12 subgingival genera and 6 gut genera significantly correlated with BP. Sixteen species under 5 genera were identified as oral-gut transmitters, illustrating the presence of oral-gut microbial transmission in HTN. Veillonella was a frequent oral-gut transmitter stably enriched in HTN participants of both cross-sectional and follow-up cohorts. Saliva from HTN participants increased BP in hypertensive mice. Human saliva-derived Veillonella successfully colonized in mouse gut, more abundantly under HTN condition.<br><br>CONCLUSIONS: PD and oral microbiota are strongly associated with HTN, likely through oral-gut transmission of microbes. Ectopic colonization of saliva-derived Veillonella in the gut may aggravate HTN. Therefore, precise manipulations of oral microbiota and/or oral-gut microbial transmission may be useful strategies for better prevention and treatment of HTN.}, }
@article {pmid36572917, year = {2022}, author = {Mhuireach, G&#xc1; and Fahimipour, AK and Vandegrift, R and Muscarella, ME and Hickey, R and Bateman, AC and Van Den Wymelenberg, KG and Bohannan, BJM}, title = {Temporary establishment of bacteria from indoor plant leaves and soil on human skin.}, journal = {Environmental microbiome}, volume = {17}, number = {1}, pages = {61}, pmid = {36572917}, issn = {2524-6372}, support = {G-2015-14023//Alfred P. Sloan Foundation/ ; }, abstract = {BACKGROUND: Plants are found in a large percentage of indoor environments, yet the potential for bacteria associated with indoor plant leaves and soil to colonize human skin remains unclear. We report results of experiments in a controlled climate chamber to characterize bacterial communities inhabiting the substrates and leaves of five indoor plant species, and quantify microbial transfer dynamics and residence times on human skin following simulated touch contact events. Controlled bacterial propagule transfer events with soil and leaf donors were applied to the arms of human occupants and repeatedly measured over a 24-h period using 16S rRNA gene amplicon sequencing.<br><br>RESULTS: Substrate samples had greater biomass and alpha diversity compared to leaves and baseline skin bacterial communities, as well as dissimilar taxonomic compositions. Despite these differences in donor community diversity and biomass, we observed repeatable patterns in the dynamics of transfer events. Recipient human skin bacterial communities increased in alpha diversity and became more similar to donor communities, an effect which, for soil contact only, persisted for at least 24 h. Washing with soap and water effectively returned communities to their pre-perturbed state, although some abundant soil taxa resisted removal through washing.<br><br>CONCLUSIONS: This study represents an initial characterization of bacterial relationships between humans and indoor plants, which represent a potentially valuable element of biodiversity in the built environment. Although environmental microbiota are unlikely to permanently colonize skin following a single contact event, repeated or continuous exposures to indoor biodiversity may be increasingly relevant for the functioning and diversity of the human microbiome as urbanization continues.}, }
@article {pmid36569851, year = {2022}, author = {Blázquez-Bondia, C and Parera, M and Català-Moll, F and Casadellà, M and Elizalde-Torrent, A and Aguiló, M and Espadaler-Mazo, J and Santos, JR and Paredes, R and Noguera-Julian, M}, title = {Probiotic effects on immunity and microbiome in HIV-1 discordant patients.}, journal = {Frontiers in immunology}, volume = {13}, number = {}, pages = {1066036}, pmid = {36569851}, issn = {1664-3224}, mesh = {Humans ; *HIV-1 ; Lipopolysaccharide Receptors ; *Probiotics/therapeutic use ; Prebiotics ; *Microbiota ; }, abstract = {BACKGROUND: Some HIV-1 infected patients are unable to completely recover normal CD4+ T-cell (CD4+) counts after achieving HIV-1 suppression with combined Antiretroviral Therapy (cART), hence being classified as immuno-discordant. The human microbiome plays a crucial role in maintaining immune homeostasis and is a potential target towards immune reconstitution.<br><br>SETTING: RECOVER (NCT03542786) was a double-blind placebo-controlled clinical trial designed to evaluate if the novel probiotic i3.1 (AB-Biotics, Sant Cugat del Vall&#xe8;s, Spain) was able to improve immune reconstitution in HIV-1 infected immuno-discordant patients with stable cART and CD4+ counts <500 cells/mm3. The mixture consisted of two strains of L. plantarum and one of P. acidilactici, given with or without a fiber-based prebiotic.<br><br>METHODS: 71 patients were randomized 1:2:2 to Placebo, Probiotic or probiotic + prebiotic (Synbiotic), and were followed over 6 months + 3-month washout period, in which changes on systemic immune status and gut microbiome were evaluated. Primary endpoints were safety and tolerability of the investigational product. Secondary endpoints were changes on CD4+ and CD8+ T-cell (CD8+) counts, inflammation markers and faecal microbiome structure, defined by alpha diversity (Gene Richness), beta diversity (Bray-Curtis) and functional profile. Comparisons across/within groups were performed using standard/paired Wilcoxon test, respectively.<br><br>RESULTS: Adverse event (AE) incidence was similar among groups (53%, 33%, and 55% in the Placebo, Probiotic and Synbiotic groups, respectively, the most common being grade 1 digestive AEs: flatulence, bloating and diarrhoea. Two grade 3 AEs were reported, all in the Synbiotic group: abdominal distension (possibly related) and malignant lung neoplasm (unrelated), and 1 grade 4&#xa0;AE in the Placebo: hepatocarcinoma (unrelated). Synbiotic exposure was associated with a higher increase in CD4+/CD8+ T-cell (CD4/CD8) ratio at 6 months vs baseline (median=0.76(IQR=0.51) vs 0.72(0. 45), median change= 0.04(IQR=0.19), p = 0.03). At month 9, the Synbiotic group had a significant increase in CD4/CD8 ratio (0.827(0.55) vs 0.825(0.53), median change = 0.04(IQR=0.15), p= 0.02) relative to baseline, and higher CD4+ counts (447 (157) vs. 342(73) counts/ml, p = 0.03), and lower sCD14 values (2.16(0.67) vs 3.18(0.8), p = 0.008) than Placebo. No effect in immune parameters was observed in the Probiotic arm. None of the two interventions modified microbial gene richness (alpha diversity). However, intervention as categorical variable was associated with slight but significant effect on Bray-Curtis distance variance (Adonis R2 = 0.02, p = 0.005). Additionally, at month 6, Synbiotic intervention was associated with lower pathway abundances vs Placebo of Assimilatory Sulphate Reduction (8.79&#xb7;10[-6] (1.25&#xb7;10[-5]) vs. 1.61&#xb7;10[-5] (2.77&#xb7;10[-5]), p = 0.03) and biosynthesis of methionine (2.3&#xb7;10[-5] (3.17&#xb7;10[-5]) vs. 4&#xb7;10[-5] (5.66&#xb7;10[-5]), p = 0.03) and cysteine (1.83&#xb7;10[-5] (2.56&#xb7;10[-5]) vs. 3.3&#xb7;10[-5] (4.62&#xb7;10[-5)], p = 0.03). At month 6, probiotic detection in faeces was associated with significant decreases in C Reactive Protein (CRP) vs baseline (11.1(22) vs. 19.2(66), median change= -2.7 (13.2) ug/ml, p = 0.04) and lower IL-6 values (0.58(1.13) vs. 1.17(1.59) ug/ml, p = 0.02) when compared with samples with no detectable probiotic. No detection of the probiotic was associated with higher CD4/CD8 ratio at month 6 vs baseline (0.718(0.57) vs. 0.58(0.4), median change = 0.4(0.2), p = 0.02). After washout, probiotic non-detection was also associated with a significant increase in CD4+ counts (457(153) vs. 416(142), median change = 45(75), counts/ml, p = 0.005) and CD4/CD8 ratio (0.67(0.5) vs 0.59(0.49), median change = 0.04 (0.18), p = 0.02).<br><br>CONCLUSION: A synbiotic intervention with L. plantarum and P. acidilactici was safe and led to small increases in CD4/CD8 ratio and minor reductions in sCD14 of uncertain clinical significance. A probiotic with the same composition was also safe but did not achieve any impact on immune parameters or faecal microbiome composition.}, }
@article {pmid36569196, year = {2022}, author = {Patpatia, S and Schaedig, E and Dirks, A and Paasonen, L and Skurnik, M and Kiljunen, S}, title = {Rapid hydrogel-based phage susceptibility test for pathogenic bacteria.}, journal = {Frontiers in cellular and infection microbiology}, volume = {12}, number = {}, pages = {1032052}, pmid = {36569196}, issn = {2235-2988}, mesh = {Humans ; *Bacteriophages ; Hydrogels/pharmacology ; Gelatin/pharmacology ; Hyaluronic Acid/pharmacology ; Staphylococcus aureus ; Escherichia coli ; }, abstract = {Phage therapy is one alternative to cure infections caused by antibiotic resistant bacteria. Due to the narrow host range of phages, hundreds to thousands of phages are required to cover the diversity of bacterial pathogens. In personalized phage therapy, fast selection of the phages for individual patients is essential for successful therapy. The aims of this study were to set up a rapid hydrogel-based liquid phage susceptibility assay (PST) for the selection of phages for therapeutic use and to establish a "ready-to-screen" plate concept, where phages are readily stored in hydrogel as small droplets in microtiter plate wells. We first tested four commercially available hydrogels (GrowDex, Askina, Purilon, and Intrasite) for their suitability as phage matrices in PSTs with four phages, two of which infecting Escherichia coli and two Staphylococcus aureus. Of these four hydrogels, GrowDex was the best matrix for PST, as it did not inhibit bacterial growth, released phages quickly when mixed with bacterial culture, and maintained phage viability well. We then optimized the assay for both optical density and microscopy readers using GrowDex as matrix with 23 bacterial strains representing 10 different species and 23 phages possessing different morphologies and genome sizes. When the bacterial growth was monitored by microscopy reader, the PST was executed in just 3 hours, and there was no need for overnight culturing bacterial cells prior to the assay, whereas using optical density reader, bacteria had to be pre-cultured overnight, and the assay time was five hours. Finally, we evaluated the effect of three different chemical stabilizers (trehalose, hyaluronic acid, and gelatin) in a six-month stability assay with six model phages. These phages assay behaved very differently in respect to the chemical stabilizers, and there was not a single stabilizer suitable for all phages. However, when gelatin (0.01%) or hyaluronic acid (0.2 mg/ml) was used as stabilizer, all tested phages were still considered as positives in PST after a six-month storage in 1 ml volume. In "ready-to-screen" plates, the differences in phage stabilities were even more profound, varying from two to six months for the most and least stable phages, respectively.}, }
@article {pmid36567346, year = {2023}, author = {Leão, I and de Carvalho, TB and Henriques, V and Ferreira, C and Sampaio-Maia, B and Manaia, CM}, title = {Pseudomonadota in the oral cavity: a glimpse into the environment-human nexus.}, journal = {Applied microbiology and biotechnology}, volume = {107}, number = {2-3}, pages = {517-534}, pmid = {36567346}, issn = {1432-0614}, support = {PTDC/CTA-AMB/28196/2017//European Regional Development Fund/ ; PTDC/MEC-MCI/29777/2017//European Regional Development Fund/ ; }, mesh = {Humans ; *Mouth/microbiology ; Bacteria/genetics ; *Microbiota ; Anti-Bacterial Agents ; Klebsiella ; }, abstract = {The phylum Pseudomonadota is amongst the most represented in the environment, with a comparatively lower prevalence in the human oral cavity. The ubiquity of Pseudomonadota and the fact that the oral cavity is the most likely entry portal of bacteria from external sources underlie the need to better understand its occurrence in the interface environment-humans. Yet, the relevance oral Pseudomonadota is largely underexplored in the scientific literature, a gap that this review aims at addressing by making, for the first time, an overview of the diversity and ecology of Pseudomonadota in the oral cavity. The screening of scientific literature and human microbiome databases unveiled 1328 reports of Pseudomonadota in the oral cavity. Most of these belonged to the classes Beta- and Gammaproteobacteria, mainly to the families Neisseriaceae, Campylobacteriaceae, and Pasteurelaceae. Others also regularly reported include genera such as Enterobacter, Klebsiella, Acinetobacter, Escherichia, Burkholderia, or Citrobacter, whose members have high potential to acquire virulence and antibiotic resistance genes. This review provides evidence that clinically relevant environmental Pseudomonadota may colonize humans via oral cavity. The need for further investigation about Pseudomonadota at the environment-oral cavity interface and their role as vectors potentially involved in virulence and antibiotic resistance transmission is demonstrated. KEY POINTS: • Neisseriaceae, Campylobacteriaceae, and Pasteurelaceae are part of the core oral microbiome • Enterobacteriaceae, Acinetobacter, or Burkholderia are frequent in the oral microbiome • Gut dysbiosis may be associated with colonization by ubiquitous oral Pseudomonadota.}, }
@article {pmid36566203, year = {2022}, author = {Dang, T and Kumaishi, K and Usui, E and Kobori, S and Sato, T and Toda, Y and Yamasaki, Y and Tsujimoto, H and Ichihashi, Y and Iwata, H}, title = {Stochastic variational variable selection for high-dimensional microbiome data.}, journal = {Microbiome}, volume = {10}, number = {1}, pages = {236}, pmid = {36566203}, issn = {2049-2618}, mesh = {Humans ; Bayes Theorem ; Algorithms ; *Microbiota/genetics ; *Gastrointestinal Microbiome/genetics ; Metagenomics ; }, abstract = {BACKGROUND: The rapid and accurate identification of a minimal-size core set of representative microbial species plays an important role in the clustering of microbial community data and interpretation of clustering results. However, the huge dimensionality of microbial metagenomics datasets is a major challenge for the existing methods such as Dirichlet multinomial mixture (DMM) models. In the approach of the existing methods, the computational burden of identifying a small number of representative species from a large number of observed species remains a challenge.<br><br>RESULTS: We propose a novel approach to improve the performance of the widely used DMM approach by combining three ideas: (i) we propose an indicator variable to identify representative operational taxonomic units that substantially contribute to the differentiation among clusters; (ii) to address the computational burden of high-dimensional microbiome data, we propose a stochastic variational inference, which approximates the posterior distribution using a controllable distribution called variational distribution, and stochastic optimization algorithms for fast computation; and (iii) we extend the finite DMM model to an infinite case by considering Dirichlet process mixtures and estimating the number of clusters as a variational parameter. Using the proposed method, stochastic variational variable selection (SVVS), we analyzed the root microbiome data collected in our soybean field experiment, the human gut microbiome data from three published datasets of large-scale case-control studies and the healthy human microbiome data from the Human Microbiome Project.<br><br>CONCLUSIONS: SVVS demonstrates a better performance and significantly faster computation than those of the existing methods in all cases of testing datasets. In particular, SVVS is the only method that can analyze massive high-dimensional microbial data with more than 50,000 microbial species and 1000 samples. Furthermore, a core set of representative microbial species is identified using SVVS that can improve the interpretability of Bayesian mixture models for a wide range of microbiome studies. Video Abstract.}, }
@article {pmid36566175, year = {2022}, author = {Zhang, J and Ma, C and Qin, H and Wang, Z and Zhu, C and Liu, X and Hao, X and Liu, J and Li, L and Cai, Z}, title = {Construction and validation of a metabolic-related genes prognostic model for oral squamous cell carcinoma based on bioinformatics.}, journal = {BMC medical genomics}, volume = {15}, number = {1}, pages = {269}, pmid = {36566175}, issn = {1755-8794}, support = {ZR2021MH033//the Science and Technology Foundation of Shandong Province/ ; 2018M632679//China Postdoctoral Science Foundation/ ; 2021M024//Traditional Chinese Medicine Science and Technology Project of Shandong Province/ ; }, mesh = {Humans ; *Carcinoma, Squamous Cell/genetics ; Squamous Cell Carcinoma of Head and Neck ; Prognosis ; *Mouth Neoplasms/genetics ; Computational Biology ; *Head and Neck Neoplasms ; }, abstract = {BACKGROUND: Oral squamous cell carcinoma (OSCC) accounts for a frequently-occurring head and neck cancer, which is characterized by high rates of morbidity and mortality. Metabolism-related genes (MRGs) show close association with OSCC development, metastasis and progression, so we constructed an MRGs-based OSCC prognosis model for evaluating OSCC prognostic outcome.<br><br>METHODS: This work obtained gene expression profile as well as the relevant clinical information from the The Cancer Genome Atlas (TCGA) database, determined the MRGs related to OSCC by difference analysis, screened the prognosis-related MRGs by performing univariate Cox analysis, and used such identified MRGs for constructing the OSCC prognosis prediction model through Lasso-Cox regression. Besides, we validated the model with the GSE41613 dataset based on Gene Expression Omnibus (GEO) database.<br><br>RESULTS: The present work screened 317 differentially expressed MRGs from the database, identified 12 OSCC prognostic MRGs through univariate Cox regression, and then established a clinical prognostic model composed of 11 MRGs by Lasso-Cox analysis. Based on the optimal risk score threshold, cases were classified as low- or high-risk group. As suggested by Kaplan-Meier (KM) analysis, survival rate was obviously different between the two groups in the TCGA training set (P&#x2009;<&#x2009;0.001). According to subsequent univariate and multivariate Cox regression, risk score served as the factor to predict prognosis relative to additional clinical features (P&#x2009;<&#x2009;0.001). Besides, area under ROC curve (AUC) values for patient survival at 1, 3 and 5&#xa0;years were determined as 0.63, 0.70, and 0.76, separately, indicating that the prognostic model has good predictive accuracy. Then, we validated this clinical prognostic model using GSE41613. To enhance our model prediction accuracy, age, gender, risk score together with TNM stage were incorporated in a nomogram. As indicated by results of ROC curve and calibration curve analyses, the as-constructed nomogram had enhanced prediction accuracy compared with clinicopathological features alone, besides, combining clinicopathological characteristics with risk score contributed to predicting patient prognosis and guiding clinical decision-making.<br><br>CONCLUSION: In this study, 11 MRGs prognostic models based on TCGA database showed superior predictive performance and had a certain clinical application prospect in guiding individualized.}, }
@article {pmid36566099, year = {2023}, author = {Mishra, K and Isali, I and Sindhani, M and Prunty, M and Bell, S and Mahran, A and Damiani, G and Ghannoum, M and Retuerto, M and Kutikov, A and Ross, J and Woo, LL and Abbosh, PH and Bukavina, L}, title = {Characterization of Changes in Penile Microbiome Following Pediatric Circumcision.}, journal = {European urology focus}, volume = {9}, number = {4}, pages = {669-680}, doi = {10.1016/j.euf.2022.12.007}, pmid = {36566099}, issn = {2405-4569}, mesh = {United States ; Male ; Infant ; Humans ; Child ; Phylogeny ; *Gastrointestinal Microbiome ; *Microbiota/genetics ; *Mycobiome ; Inflammation ; }, abstract = {BACKGROUND: While microbiome and host regulation contribute independently to many disease states, it is unclear how circumcision in pediatric population influences subsequent changes in penile microbiome.<br><br>OBJECTIVE: Our study aims to analyze jointly paired taxonomic profiles and assess pathways implicated in inflammation, barrier protection, and energy metabolism.<br><br>We analyzed 11 paired samples, periurethral collection, before and after circumcision, to generate microbiome and mycobiome profiling. Sample preparation of 16S ribosomal RNA and internal transcribed spacer sequencing was adapted from the methods developed by the National Institutes of Health Human Microbiome Project.<br><br>We obtained the predictive functional attributes of the microbial communities between samples using Silva-Tax4Fun and the Greengenes-Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) approach. The predictive functioning of the microbial communities was determined by linearly combining the normalized taxonomic abundances into the precomputed association matrix of Kyoto Encyclopedia of Genes and Genomes orthology reference profiles.<br><br>RESULTS AND LIMITATIONS: Several notable microbiome and mycobiome compositional differences were observed between pre- and postcircumcision patients. Pairwise comparisons across taxa revealed a significant decrease (p&#xa0;<&#xa0;0.05, false discovery rate corrected) of microbiome organisms (Clostridiales, Bacteroidales, and Campylobacterales) and mycobiome (Saccharomycetales and Pleosporales) following circumcision. A total of 14 pathways were found to differ in abundance between the pre- and postcircumcision groups (p&#xa0;<&#xa0;0.005, false discovery rate <0.1 and linear discriminant analysis score >3; five enriched and nine depleted). The pathways reduced after circumcision were mostly involved with amino acid and glucose metabolism, while pathways prior to circumcision were enriched in genetic information processing and transcription processes. As expected, enrichment in methyl-accepting chemotaxis protein, an integral membrane protein involved in directed motility of microbes to chemical cues and environment, occurred prior to circumcision, while the filamentous hemagglutinin pathway (a strong immunogenic protein) was depleted after circumcision CONCLUSIONS: Our results offer greater insight into the host-microbiota relationship of penile circumcision and may serve to lay the groundwork for future studies focused on drivers of inflammation, infection, and oncogenesis.<br><br>PATIENT SUMMARY: Our study showed a significant reduction in bacteria and fungi after circumcision, particularly anaerobic bacteria, which are known to be potential inducers of inflammation and cancer. This is the first study of its kind showing the changes in microbiome after circumcision, and some of the changes that occur in healthy infants after circumcision that may explain the differences in cancer and inflammatory disorders in adulthood.}, }
@article {pmid36564884, year = {2022}, author = {Lunjani, N and Walsh, LJ and Venter, C and Power, M and MacSharry, J and Murphy, DM and O'Mahony, L}, title = {Environmental influences on childhood asthma-The effect of diet and microbiome on asthma.}, journal = {Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology}, volume = {33}, number = {12}, pages = {e13892}, pmid = {36564884}, issn = {1399-3038}, mesh = {Child ; Humans ; *Asthma/etiology ; *Microbiota ; Diet ; *Gastrointestinal Microbiome ; Immune System ; }, abstract = {Early life dietary patterns and timely maturation of mucosa-associated microbial communities are important factors influencing immune development and for establishing robust immune tolerance networks. Microbial fermentation of dietary components in vivo generates a vast array of molecules, some of which are integral components of the molecular circuitry that regulates immune and metabolic functions. These in turn protect against aberrant inflammatory processes and promote effector immune responses that quickly eliminate pathogens. Multiple studies suggest that changes in dietary habits, altered microbiome composition, and microbial metabolism are associated with asthma risk and disease severity. While it remains unclear whether these microbiome alterations are a cause or consequence of dysregulated immune responses, there is significant potential for using diet in targeted manipulations of the gut microbiome and its metabolic functions in promoting immune health. In this article, we will summarize our knowledge to date on the role of dietary patterns and microbiome activities on immune responses within the airways. Given the malleability of the human microbiome, its integration into the immune system, and its responsiveness to diet, this makes it a highly attractive target for therapeutic and nutritional intervention in children with asthma.}, }
@article {pmid36561630, year = {2023}, author = {Raudoniute, J and Bironaite, D and Bagdonas, E and Kulvinskiene, I and Jonaityte, B and Danila, E and Aldonyte, R}, title = {Human airway and lung microbiome at the crossroad of health and disease (Review).}, journal = {Experimental and therapeutic medicine}, volume = {25}, number = {1}, pages = {18}, pmid = {36561630}, issn = {1792-1015}, abstract = {The evolving field of the microbiome and microbiota has become a popular research topic. The human microbiome is defined as a new organ and is considered a living community of commensal, symbiotic and pathogenic microorganisms within a certain body space. The term 'microbiome' is used to define the entire genome of the microbiota. Bacteria, archaea, fungi, algae and small protists are all members of the microbiota, followed by phages, viruses, plasmids and mobile genetic elements. The composition, heterogeneity and dynamics of microbiomes in time and space, their stability and resistance, essential characteristics and key participants, as well as interactions within the microbiome and with the host, are crucial lines of investigation for the development of successful future diagnostics and therapies. Standardization of microbiome studies and harmonized comparable methodologies are required for the transfer of knowledge from fundamental science into the clinic. Human health is dependent on microbiomes and achieved by nurturing beneficial resident microorganisms and their interplay with the host. The present study reviewed scientific knowledge on the major components of the human respiratory microbiome, i.e. bacteria, viruses and fungi, their symbiotic and parasitic roles, and, also, major diseases of the human respiratory tract and their microbial etiology. Bidirectional relationships regulate microbial ecosystems and host susceptibility. Moreover, environmental insults render host tissues and microbiota disease-prone. The human respiratory microbiome reflects the ambient air microbiome. By understanding the human respiratory microbiome, potential therapeutic strategies may be proposed.}, }
@article {pmid36560636, year = {2022}, author = {Ács, N and Holohan, R and Dunne, LJ and Fernandes, AR and Clooney, AG and Draper, LA and Ross, RP and Hill, C}, title = {Comparing In Vitro Faecal Fermentation Methods as Surrogates for Phage Therapy Application.}, journal = {Viruses}, volume = {14}, number = {12}, pages = {}, pmid = {36560636}, issn = {1999-4915}, mesh = {Humans ; Fermentation ; *Phage Therapy ; Feces ; Gastrointestinal Tract ; *Bacteriophages/genetics ; }, abstract = {The human microbiome and its importance in health and disease have been the subject of numerous research articles. Most microbes reside in the digestive tract, with up to 10[12] cells per gram of faecal material found in the colon. In terms of gene number, it has been estimated that the gut microbiome harbours >100 times more genes than the human genome. Several human intestinal diseases are strongly associated with disruptions in gut microbiome composition. Less studied components of the gut microbiome are the bacterial viruses called bacteriophages that may be present in numbers equal to or greater than the prokaryotes. Their potential to lyse their bacterial hosts, or to act as agents of horizontal gene transfer makes them important research targets. In this study in vitro faecal fermentation systems were developed and compared for their ability to act as surrogates for the human colon. Changes in bacterial and viral composition occurred after introducing a high-titre single phage preparation both with and without a known bacterial host during the 24 h-long fermentation. We also show that during this timeframe 50 mL plastic tubes can provide data similar to that generated in a sophisticated faecal fermenter system. This knowledge can guide us to a better understanding of the short-term impact of bacteriophage transplants on the bacteriomes and viromes of human recipients.}, }
@article {pmid36557565, year = {2022}, author = {Gonçalves, MFM and Fernandes, &#xc2;R and Rodrigues, AG and Lisboa, C}, title = {Microbiome in Male Genital Mucosa (Prepuce, Glans, and Coronal Sulcus): A Systematic Review.}, journal = {Microorganisms}, volume = {10}, number = {12}, pages = {}, pmid = {36557565}, issn = {2076-2607}, support = {NORTE-01-0145-FEDER-000057//Horizon Europe programme and Norte 2020/ ; }, abstract = {The human body represents a complex and diverse reservoir of microorganisms. Although the human microbiome remains poorly characterized and understood, it should not be underestimated, since recent studies have highlighted its importance in health. This is especially evident when considering microbiota in the male reproductive system, responsible for men’s fertility and sexual behavior. Therefore, the aim of this systematic review is to provide an overview of the microbial communities of the healthy male genital mucosa and its role in disease. This study was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The search was limited to the English language and studies published until August 2022 that included culture-independent techniques for microbiome characterization in male genital mucosa. Ten articles were included. The bacterial composition of the male genital mucosa consists of several genera including Prevotella, Finegoldia, Peptoniphilus, Staphylococcus, Corynebacterium, and Anaerococcus, suggesting that the male genital microbiome composition shows similarities with the adjacent anatomical sites and is related with sexual intercourse. Moreover, male circumcision appears to influence the penile microbiome. Despite the lack of knowledge on the male genital mucosa microbiome in disease, it was reported that Staphylococcus warneri and Prevotella bivia were associated with balanoposthitis, whereas Enterobacteriaceae, Prevotella, and Fusobacterium were more abundant in male genital lichen sclerosus. The limited data and paucity of prospective controlled studies highlight the need for additional studies and established criteria for sampling methods and the microbiome assay procedure. Such a consensus would foster the knowledge about the composition of the genital microbiome of healthy males and its role in disease.}, }
@article {pmid36555624, year = {2022}, author = {Levi Mortera, S and Marzano, V and Vernocchi, P and Matteoli, MC and Guarrasi, V and Gardini, S and Del Chierico, F and Rapini, N and Deodati, A and Fierabracci, A and Cianfarani, S and Putignani, L}, title = {Functional and Taxonomic Traits of the Gut Microbiota in Type 1 Diabetes Children at the Onset: A Metaproteomic Study.}, journal = {International journal of molecular sciences}, volume = {23}, number = {24}, pages = {}, pmid = {36555624}, issn = {1422-0067}, mesh = {Adolescent ; Humans ; Child ; Aged ; *Diabetes Mellitus, Type 1 ; *Gastrointestinal Microbiome/physiology ; RNA, Ribosomal, 16S/genetics ; *Insulin-Secreting Cells ; Insulin, Regular, Human ; Insulin ; }, abstract = {Type 1 diabetes (T1D) is a chronic autoimmune metabolic disorder with onset in pediatric/adolescent age, characterized by insufficient insulin production, due to a progressive destruction of pancreatic β-cells. Evidence on the correlation between the human gut microbiota (GM) composition and T1D insurgence has been recently reported. In particular, 16S rRNA-based metagenomics has been intensively employed in the last decade in a number of investigations focused on GM representation in relation to a pre-disease state or to a response to clinical treatments. On the other hand, few works have been published using alternative functional omics, which is more suitable to provide a different interpretation of such a relationship. In this work, we pursued a comprehensive metaproteomic investigation on T1D children compared with a group of siblings (SIBL) and a reference control group (CTRL) composed of aged matched healthy subjects, with the aim of finding features in the T1D patients' GM to be related with the onset of the disease. Modulated metaproteins were found either by comparing T1D with CTRL and SIBL or by stratifying T1D by insulin need (IN), as a proxy of β-cells damage, showing some functional and taxonomic traits of the GM, possibly related to the disease onset at different stages of severity.}, }
@article {pmid36549660, year = {2023}, author = {Merritt, J and Kreth, J}, title = {Illuminating the oral microbiome and its host interactions: tools and approaches for molecular microbiology studies.}, journal = {FEMS microbiology reviews}, volume = {47}, number = {6}, pages = {}, pmid = {36549660}, issn = {1574-6976}, support = {R01 DE029492/DE/NIDCR NIH HHS/United States ; R21 DE029612/DE/NIDCR NIH HHS/United States ; R35 DE028252/DE/NIDCR NIH HHS/United States ; DE022083/NH/NIH HHS/United States ; }, mesh = {Humans ; *Dysbiosis ; *Microbiota/genetics ; Bacteria/genetics ; Symbiosis ; }, abstract = {Advancements in DNA sequencing technologies within the last decade have stimulated an unprecedented interest in the human microbiome, largely due the broad diversity of human diseases found to correlate with microbiome dysbiosis. As a direct consequence of these studies, a vast number of understudied and uncharacterized microbes have been identified as potential drivers of mucosal health and disease. The looming challenge in the field is to transition these observations into defined molecular mechanistic studies of symbiosis and dysbiosis. In order to meet this challenge, many of these newly identified microbes will need to be adapted for use in experimental models. Consequently, this review presents a comprehensive overview of the molecular microbiology tools and techniques that have played crucial roles in genetic studies of the bacteria found within the human oral microbiota. Here, we will use specific examples from the oral microbiome literature to illustrate the biology supporting these techniques, why they are needed in the field, and how such technologies have been implemented. It is hoped that this information can serve as a useful reference guide to help catalyze molecular microbiology studies of the many new understudied and uncharacterized species identified at different mucosal sites in the body.}, }
@article {pmid36547746, year = {2022}, author = {Akouris, PP and Chmiel, JA and Stuivenberg, GA and Kiattiburut, W and Bjazevic, J and Razvi, H and Grohe, B and Goldberg, HA and Burton, JP and Al, KF}, title = {Osteopontin phosphopeptide mitigates calcium oxalate stone formation in a Drosophila melanogaster model.}, journal = {Urolithiasis}, volume = {51}, number = {1}, pages = {19}, pmid = {36547746}, issn = {2194-7236}, mesh = {Animals ; *Calcium Oxalate/metabolism ; Drosophila melanogaster ; *Kidney Calculi/drug therapy/metabolism ; *Osteopontin/pharmacology/therapeutic use ; *Phosphopeptides/pharmacology/therapeutic use ; Disease Models, Animal ; }, abstract = {Kidney stone disease affects nearly one in ten individuals and places a significant economic strain on global healthcare systems. Despite the high frequency of stones within the population, effective preventative strategies are lacking and disease prevalence continues to rise. Osteopontin (OPN) is a urinary protein that can inhibit the formation of renal calculi in vitro. However, the efficacy of OPN in vivo has yet to be determined. Using an established Drosophila melanogaster model of calcium oxalate urolithiasis, we demonstrated that a 16-residue synthetic OPN phosphopeptide effectively reduced stone burden in vivo. Oral supplementation with this peptide altered crystal morphology of calcium oxalate monohydrate (COM) in a similar manner to previous in vitro studies, and the presence of the OPN phosphopeptide during COM formation and adhesion significantly reduced crystal attachment to mammalian kidney cells. Altogether, this study is the first to show that an OPN phosphopeptide can directly mitigate calcium oxalate urolithiasis formation in vivo by modulating crystal morphology. These findings suggest that OPN supplementation is a promising therapeutic approach and may be clinically useful in the management of urolithiasis in humans.}, }
@article {pmid36544495, year = {2022}, author = {Wortelboer, K and Koopen, AM and Herrema, H and de Vos, WM and Nieuwdorp, M and Kemper, EM}, title = {From fecal microbiota transplantation toward next-generation beneficial microbes: The case of Anaerobutyricum soehngenii.}, journal = {Frontiers in medicine}, volume = {9}, number = {}, pages = {1077275}, pmid = {36544495}, issn = {2296-858X}, abstract = {The commensal gut microbiota is important for human health and well-being whereas deviations of the gut microbiota have been associated with a multitude of diseases. Restoration of a balanced and diverse microbiota by fecal microbiota transplantation (FMT) has emerged as a potential treatment strategy and promising tool to study causality of the microbiota in disease pathogenesis. However, FMT comes with logistical challenges and potential safety risks, such as the transfer of pathogenic microorganisms, undesired phenotypes or an increased risk of developing disease later in life. Therefore, a more controlled, personalized mixture of cultured beneficial microbes might prove a better alternative. Most of these beneficial microbes will be endogenous commensals to the host without a long history of safe and beneficial use and are therefore commonly referred to as next-generation probiotics (NGP) or live biotherapeutic products (LBP). Following a previous FMT study within our group, the commensal butyrate producer Anaerobutyricum spp. (previously named Eubacterium hallii) was found to be associated with improved insulin-sensitivity in subjects with the metabolic syndrome. After the preclinical testing with Anaerobutyricum soehngenii in mice models was completed, the strain was produced under controlled conditions and several clinical studies evaluating its safety and efficacy in humans were performed. Here, we describe and reflect on the development of A. soehngenii for clinical use, providing practical guidance for the development and testing of NGPs and reflecting on the current regulatory framework.}, }
@article {pmid36544282, year = {2023}, author = {Bai, X and Xu, Q and Zhang, W and Wang, C}, title = {The Gut-Eye Axis: Correlation Between the Gut Microbiota and Autoimmune Dry Eye in Individuals With Sjögren Syndrome.}, journal = {Eye &amp; contact lens}, volume = {49}, number = {1}, pages = {1-7}, doi = {10.1097/ICL.0000000000000953}, pmid = {36544282}, issn = {1542-233X}, mesh = {Humans ; *Sjogren's Syndrome/complications ; *Gastrointestinal Microbiome ; *Autoimmune Diseases/complications/therapy ; Dysbiosis/complications ; *Dry Eye Syndromes/etiology/therapy ; }, abstract = {The impact of gut microbiota on human health, autoimmunity, and disease occurrence has long been recognized since the advancement of metagenomic sequencing technology has enabled a new level of perspective on the human microbiome. Emerging findings also suggest the existence of a gut-eye axis, wherein gut dysbiosis may be a crucial factor affecting the onset and progression of multiple ocular diseases. Sjögren syndrome (SS) is a chronic autoimmune disease mainly affecting the exocrine glands, primarily the lacrimal gland in the eye, resulting in severe dry eye. Although there are currently various treatments for environmental dry eye, the efficacy for SS-related autoimmune dry eye is limited, and new and more effective therapies still need to be explored. The latest studies have demonstrated that the gut microbiota plays a key role in the pathogenesis of autoimmune dry eye. This review describes the effect of gut microbiota on the ocular surface of autoimmune dry eye; introduces the presumable pathways forming the "gut dysbiosis-ocular surface-lacrimal gland axis"; discusses the advantages of restoring intestinal microecology to treat dry eye by fecal microbiota transplantation or probiotics, which are expected to provide perspectives into the correlation between the gut microbiome and dry eye; enhance our understanding of the pathogenesis in autoimmune dry eye; and be useful in the development of future interventions of dry eye by regulating the gut microbiota.}, }
@article {pmid36541798, year = {2023}, author = {Gupta, S and Poret, AJ and Hashemi, D and Eseonu, A and Yu, SH and D'Gama, J and Neel, VA and Lieberman, TD}, title = {Cutaneous Surgical Wounds Have Distinct Microbiomes from Intact Skin.}, journal = {Microbiology spectrum}, volume = {11}, number = {1}, pages = {e0330022}, pmid = {36541798}, issn = {2165-0497}, support = {UL1 TR002541/TR/NCATS NIH HHS/United States ; }, mesh = {Humans ; *Surgical Wound ; Staphylococcus aureus ; Skin/microbiology ; *Microbiota ; Bacteria ; *Skin Neoplasms ; }, abstract = {Infections are relatively rare following cutaneous surgical procedures, despite the potential for wound exposure to pathogens both during surgery and throughout the healing process. Although gut commensals are believed to reduce the risk of intestinal infections, an analogous role for skin commensals has not been described. In fact, the microbiome of normally healing surgical skin wounds has not yet been profiled using culture-independent techniques. We characterized the wound microbiome in 53 patients who underwent skin cancer surgery and healed without signs or symptoms of infection. A week after surgery, several bacterial species displayed significant differences in relative abundance when compared to control, nonoperated skin from the same patient. The relative abundance of the most common bacterium found on intact skin, Cutibacterium acnes, was reduced in wounds 5-fold. Staphylococcus aureus, a frequent cause of postoperative skin infections, was enriched 6.4-fold in clinically noninfected wounds, suggesting active suppression of pathogenicity. Finally, members of the Corynebacterium genus were the dominant organism in postoperative wounds, making up 37% of the average wound microbiome. The enrichment of these bacteria in normally healing wounds suggests that they might be capable of providing colonization resistance. Future studies focused on the biological and clinical significance of the wound microbiome may shed light on normal wound healing and potential therapeutic opportunities to mitigate infection risk. IMPORTANCE Commensal bacteria on skin may limit the ability of pathogenic bacteria to cause clinically significant infections. The bacteria on healing acute wounds, which might provide such a protective effect, have not been described using culture-independent approaches in the absence of antibiotics. We compare the microbiome of wounds a week after skin cancer removal surgery with intact skin from the same patient. We find that the potentially pathogenic species S. aureus is common on these healing wounds despite the absence of symptoms or signs of infection. We report that bacteria often considered as potential skin probiotics, including Staphylococcus epidermidis, do not reach high relative abundance in wound microbiomes. In contrast, specific members of the Corynebacterium genus, rarely associated with infections, were significantly enriched in healing wounds compared to intact skin. Future work is needed to see if Corynebacterium species or derivatives thereof could be employed to lower the risk of wound infection.}, }
@article {pmid36541771, year = {2023}, author = {Bhattacharjee, D and Flores, C and Woelfel-Monsivais, C and Seekatz, AM}, title = {Diversity and Prevalence of Clostridium innocuum in the Human Gut Microbiota.}, journal = {mSphere}, volume = {8}, number = {1}, pages = {e0056922}, pmid = {36541771}, issn = {2379-5042}, support = {K01 DK111794/DK/NIDDK NIH HHS/United States ; P20 GM109094/GM/NIGMS NIH HHS/United States ; }, mesh = {Prevalence ; *Gastrointestinal Microbiome ; RNA, Ribosomal, 16S/genetics ; Firmicutes ; Humans ; *Clostridium/genetics ; }, abstract = {Clostridia are a polyphyletic group of Gram-positive, spore-forming anaerobes in the Firmicutes phylum that significantly impact metabolism and functioning of the human gastrointestinal tract. Recently, Clostridia were divided into two separate classes, Clostridia and Erysipelotrichia, based on phenotypic and 16S rRNA gene-based differences. While Clostridia include many well-known pathogenic bacteria, Erysipelotrichia remain relatively uncharacterized, particularly regarding their role as a pathogen versus commensal. Despite wide recognition as a commensal, the erysipelotrichial species Clostridium innocuum has recently been associated with various disease states. To further understand the ecological and potential virulent role of C. innocuum, we conducted a genomic comparison across 38 C. innocuum isolates and 194 publicly available genomes. Based on colony morphology, we isolated multiple C. innocuum cultivars from the feces of healthy human volunteers (n = 5). Comparison of the 16S rRNA gene of our isolates against publicly available microbiota data sets in healthy individuals suggests a high prevalence of C. innocuum across the human population (>80%). Analysis of single nucleotide polymorphisms (SNPs) across core genes and average nucleotide identify (ANI) revealed the presence of four clades among all available genomes (n = 232 total). Investigation of carbohydrate and protein utilization pathways, including comparison against the carbohydrate-activating enzyme (CAZyme) database, demonstrated inter- and intraclade differences that were further substantiated in vitro. Collectively, these data indicate genetic variance within the C. innocuum species that may help clarify its role in human disease and health. IMPORTANCE Clostridia are a group of medically important anaerobes as both commensals and pathogens. Recently, a new class of Erysipelotrichia containing a number of reassigned clostridial species has emerged, including Clostridium innocuum. Recent studies have implicated C. innocuum as a potential causative agent of diarrhea in patients from whom Clostridioides difficile could not be isolated. Using genomic and in vitro comparison, this study sought to characterize C. innocuum in the healthy human gut. Our analyses suggest that C. innocuum is a highly prevalent and diverse species, demonstrating clade-specific differences in metabolism and potential virulence. Collectively, this study is the first investigation into a broader description of C. innocuum as a human gut inhabitant.}, }
@article {pmid36541643, year = {2023}, author = {Hanttu, AM and Pekkala, S and Satokari, R and Hartikainen, AK and Arkkila, P and Pietiläinen, KH and Sutinen, JP}, title = {Gut microbiota alterations after switching from a protease inhibitor or efavirenz to raltegravir in a randomized, controlled study.}, journal = {AIDS (London, England)}, volume = {37}, number = {2}, pages = {323-332}, doi = {10.1097/QAD.0000000000003419}, pmid = {36541643}, issn = {1473-5571}, mesh = {Humans ; Raltegravir Potassium/therapeutic use ; *Anti-HIV Agents/therapeutic use ; *HIV Infections/drug therapy ; *Gastrointestinal Microbiome ; RNA, Ribosomal, 16S/genetics ; Benzoxazines/therapeutic use ; Protease Inhibitors/therapeutic use ; Inflammation/drug therapy ; }, abstract = {OBJECTIVE: To study gut microbiota before and 24 weeks after a single antiretroviral agent switch.<br><br>DESIGN: HIV-positive patients with efavirenz (EFV) or a protease inhibitor (PI)-based antiretroviral therapy (ART) were randomized to switch EFV or PI to raltegravir (RAL group, n&#x200a;=&#x200a;19) or to continue unchanged ART (EFV/PI group, n&#x200a;=&#x200a;22). Age and weight-matched HIV-negative participants (n&#x200a;=&#x200a;10) were included for comparison.<br><br>METHODS: Microbiota was analyzed using 16S rRNA sequencing. Serum intestinal fatty acid-binding protein (I-FABP) and serum lipopolysaccharide-binding protein (LBP) were measured as gut permeability markers. Three-day food diaries were collected.<br><br>RESULTS: At week 24, microbiota diversity (Chao1 index) was higher in RAL than the EFV/PI group (P&#x200a;=&#x200a;0.014), and RAL group did not differ from HIV-negative participants. In subgroup analysis switching from EFV (P&#x200a;=&#x200a;0.043), but not from a PI to RAL increased Chao1. At week 24, RAL and EFV/PI group differed in the relative abundance of Prevotella 9 (higher in RAL, P&#x200a;=&#x200a;0.01), Phascolarctobacterium and Bacteroides (lower in RAL, P&#x200a;=&#x200a;0.01 and P&#x200a;=&#x200a;0.03). Dietary intakes did not change during the study and do not explain microbiota differences. Also, I-FABP and LBP remained unchanged.<br><br>CONCLUSION: Here we demonstrate that a single ART agent switch caused microbiota alterations, most importantly, an increase in diversity with EFV to RAL switch. Previously, we reported weight gain, yet reduced inflammation in this cohort. The observed microbiota differences between RAL and EFV/PI groups may be associated with reduced inflammation and/or increase in weight. Further studies are needed to evaluate inflammatory and metabolic capacity of microbiota with ART switches.}, }
@article {pmid36537820, year = {2023}, author = {Mantegazza, G and Gargari, G and Duncan, R and Consalez, F and Taverniti, V and Riso, P and Guglielmetti, S}, title = {Ready-To-Eat Rocket Salads as Potential Reservoir of Bacteria for the Human Microbiome.}, journal = {Microbiology spectrum}, volume = {11}, number = {1}, pages = {e0297022}, pmid = {36537820}, issn = {2165-0497}, mesh = {Humans ; Food Microbiology ; Colony Count, Microbial ; *Salads/microbiology ; Agar ; RNA, Ribosomal, 16S/genetics ; Vegetables/microbiology ; Bacteria ; *Microbiota ; }, abstract = {Reportedly, Western-type diets may induce the loss of key microbial taxa within the gastrointestinal microbiota, promoting the onset of noncommunicable diseases. It was hypothesized that the consumption of raw vegetables could contribute to the maintenance of the intestinal microbial community structure. In this context, we explored bacteria associated with commercial rocket salads produced through different farming practices: traditional (conventional, organic, and integrated) and vertical farming. Viable counts of mesophilic bacteria and lactic acid bacteria (LAB) were performed on plate count agar (PCA) and de Man-Rogosa-Sharpe (MRS) agar at pH 5.7, whereas metataxonomics through 16S rRNA gene sequencing was used to profile total bacteria associated with rocket salads. We found that rocket salads from vertical farming had much fewer viable bacteria and had a bacterial community structure markedly different from that of rocket salads from traditional farming. Furthermore, although α- and β-diversity analyses did not differentiate rocket samples according to farming techniques, several bacterial taxa distinguished organic and integrated from conventional farming salads, suggesting that farming practices could affect the taxonomic composition of rocket bacterial communities. LAB were isolated from only traditional farming samples and belonged to different species, which were variably distributed among samples and could be partly associated with farming practices. Finally, the INFOGEST protocol for in vitro simulation of gastrointestinal digestion revealed that several taxonomically different rocket-associated bacteria (particularly LAB) could survive gastrointestinal transit. This study suggests that commercial ready-to-eat rocket salads harbor live bacteria that possess the ability to survive gastrointestinal transit, potentially contributing to the taxonomic structure of the human gut microbiota. IMPORTANCE Western-type diets are composed of foods with a reduced amount of naturally occurring microorganisms. It was hypothesized that a microbe-depleted diet can favor the alteration of the human intestinal microbial ecosystem, therefore contributing to the onset of chronic metabolic and immune diseases currently recognized as the most significant causes of death in the developed world. Here, we studied the microorganisms that are associated with commercial ready-to-eat rocket salads produced through different farming practices. We showed that rocket salad (a widely consumed vegetal food frequently eaten raw) may be a source of lactic acid bacteria and other microbes that can survive gastrointestinal transit, potentially increasing the biodiversity of the intestinal microbiota. This deduction may be valid for virtually all vegetal foods that are consumed raw.}, }
@article {pmid36537130, year = {2022}, author = {Balskus, EP}, title = {Elucidating the Chemistry and Biology of the Human Microbiome.}, journal = {Biochemistry}, volume = {61}, number = {24}, pages = {2777-2778}, doi = {10.1021/acs.biochem.2c00652}, pmid = {36537130}, issn = {1520-4995}, mesh = {Humans ; *Microbiota ; *Gastrointestinal Microbiome ; Biology ; }, }
@article {pmid36534203, year = {2022}, author = {Jesus, HNR and Ramos, JN and Rocha, DJPG and Alves, DA and Silva, CS and Cruz, JVO and Vieira, VV and Souza, C and Santos, LS and Navas, J and Ramos, RTJ and Azevedo, V and Aguiar, ERGR and Mattos-Guaraldi, AL and Pacheco, LGC}, title = {The pan-genome of the emerging multidrug-resistant pathogen Corynebacterium striatum.}, journal = {Functional &amp; integrative genomics}, volume = {23}, number = {1}, pages = {5}, pmid = {36534203}, issn = {1438-7948}, support = {BOL0505/2018//Funda&#xe7;&#xe3;o de Amparo &#xe0; Pesquisa do Estado da Bahia/ ; BOL0505/2018//Funda&#xe7;&#xe3;o de Amparo &#xe0; Pesquisa do Estado da Bahia/ ; CAPES-PROCAD 071/2013//Coordena&#xe7;&#xe3;o de Aperfei&#xe7;oamento de Pessoal de N&#xed;vel Superior/ ; CAPES-PROCAD 071/2013//Coordena&#xe7;&#xe3;o de Aperfei&#xe7;oamento de Pessoal de N&#xed;vel Superior/ ; CAPES-PROCAD 071/2013//Coordena&#xe7;&#xe3;o de Aperfei&#xe7;oamento de Pessoal de N&#xed;vel Superior/ ; CAPES-PROCAD 071/2013//Coordena&#xe7;&#xe3;o de Aperfei&#xe7;oamento de Pessoal de N&#xed;vel Superior/ ; CAPES-PROCAD 071/2013//Coordena&#xe7;&#xe3;o de Aperfei&#xe7;oamento de Pessoal de N&#xed;vel Superior/ ; CAPES-PROCAD 071/2013//Coordena&#xe7;&#xe3;o de Aperfei&#xe7;oamento de Pessoal de N&#xed;vel Superior/ ; CNPq N&#xba; 09/2018//Conselho Nacional de Desenvolvimento Cient&#xed;fico e Tecnol&#xf3;gico/ ; CNPq N&#xba; 09/2018//Conselho Nacional de Desenvolvimento Cient&#xed;fico e Tecnol&#xf3;gico/ ; CNPq N&#xba; 09/2018//Conselho Nacional de Desenvolvimento Cient&#xed;fico e Tecnol&#xf3;gico/ ; MCT/FINEP/CT-INFRA01/2013//Financiadora de Estudos e Projetos/ ; }, mesh = {Humans ; *Corynebacterium ; *Anti-Bacterial Agents ; Phenotype ; Virulence Factors/genetics ; Drug Resistance, Multiple, Bacterial/genetics ; Microbial Sensitivity Tests ; }, abstract = {Corynebacterium striatum, a common constituent of the human skin microbiome, is now considered an emerging multidrug-resistant pathogen of immunocompromised and chronically ill patients. However, little is known about the molecular mechanisms in the transition from colonization to the multidrug-resistant (MDR) invasive phenotype in clinical isolates. This study performed a comprehensive pan-genomic analysis of C. striatum, including isolates from "normal skin microbiome" and from MDR infections, to gain insights into genetic factors contributing to pathogenicity and multidrug resistance in this species. For this, three novel genome sequences were obtained from clinical isolates of C. striatum of patients from Brazil, and other 24 complete or draft C. striatum genomes were retrieved from GenBank, including the ATCC6940 isolate from the Human Microbiome Project. Analysis of C. striatum strains demonstrated the presence of an open pan-genome (α = 0.852803) containing 3816 gene families, including 15 antimicrobial resistance (AMR) genes and 32 putative virulence factors. The core and accessory genomes included 1297 and 1307 genes, respectively. The identified AMR genes are primarily associated with resistance to aminoglycosides and tetracyclines. Of these, 66.6% are present in genomic islands, and four AMR genes, including aac(6')-ib7, are located in a class 1-integron. In conclusion, our data indicated that C. striatum possesses genomic characteristics favorable to the invasive phenotype, with high genomic plasticity, a robust genetic arsenal for iron acquisition, and important virulence determinants and AMR genes present in mobile genetic elements.}, }
@article {pmid36530685, year = {2022}, author = {Tozzo, P and Delicati, A and Caenazzo, L}, title = {Human microbiome and microbiota identification for preventing and controlling healthcare-associated infections: A systematic review.}, journal = {Frontiers in public health}, volume = {10}, number = {}, pages = {989496}, pmid = {36530685}, issn = {2296-2565}, mesh = {Humans ; *Cross Infection/prevention &amp; control/microbiology ; *Microbiota ; Delivery of Health Care ; }, abstract = {OBJECTIVE: This systematic review describes the role of the human microbiome and microbiota in healthcare-associated infections (HAIs). Studies on the microbiota of patients, healthcare environment (HE), medical equipment, or healthcare workers (HCW) and how it could be transmitted among the different subjects will be described in order to define alarming risk factors for HAIs spreading and to identify strategies for HAIs control or prevention.<br><br>METHODS: This review was performed in adherence to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. After retrieval in databases, identification, and screening of available records, 36 published studies were considered eligible and included in the review.<br><br>RESULTS: A multifaceted approach is required and the analyses of the many factors related to human microbiota, which can influence HAIs onset, could be of paramount importance in their prevention and control. In this review, we will focus mainly on the localization, transmission, and prevention of ESKAPE (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species) bacteria and Clostridium difficile which are the most common pathogens causing HAIs.<br><br>CONCLUSIONS: Healthcare workers' microbiota, patient's microbiota, environmental and medical equipment microbiota, ecosystem characteristics, ways of transmission, cleaning strategies, and the microbial resistome should be taken into account for future studies on more effective preventive and therapeutic strategies against HAIs.}, }
@article {pmid36527169, year = {2024}, author = {Zhang, Y and Zhang, H and Xu, T and Zeng, L and Liu, F and Huang, X and Liu, Q}, title = {Interactions among microorganisms open up a new world for anti-infectious therapy.}, journal = {The FEBS journal}, volume = {291}, number = {8}, pages = {1615-1631}, doi = {10.1111/febs.16705}, pmid = {36527169}, issn = {1742-4658}, support = {202110403093//National Innovation and Entrepreneurship Training Program for College Students/ ; 31760261//National Natural Science Foundation of China/ ; 32060040//National Natural Science Foundation of China/ ; 32260193//National Natural Science Foundation of China/ ; 82203032//National Natural Science Foundation of China/ ; 20202BAB206062//Natural Science Foundation of Jiangxi Province/ ; 20212BCJ23036//Training Plan for Academic and Technical Leaders of Major Disciplines in Jiangxi Province-Youth Talent Project/ ; }, mesh = {Humans ; *Microbiota ; *Gastrointestinal Microbiome ; Symbiosis ; Fungi ; Bacteria/genetics ; }, abstract = {The human microbiome, containing bacteria, fungi, and viruses, is a community that coexists peacefully with humans most of the time, but with the potential to cause disease under certain conditions. When the environment changes or certain stimuli are received, microbes may interact with each other, causing or increasing the severity of disease in a host. With the appropriate methods, we can make these microbiota work for us, creating new applications for human health. This review discusses the wide range of interactions between microorganisms that result in an increase in susceptibility to, severity of, and mortality of diseases, and also briefly introduces how microorganisms interact with each other directly or indirectly. The study of microbial interactions and their mechanisms has revealed a new world of treatments for infectious disease. The regulation of the balance between intestinal flora, the correct application of probiotics, and the development of effective drugs by symbiosis all demonstrate the great contributions of the microbiota to human health and its powerful potential value. Consequently, the study of interactions between microorganisms plays an essential role in identifying the causes of diseases and the development of treatments.}, }
@article {pmid36525272, year = {2022}, author = {Lahtinen, P and Juuti, A and Luostarinen, M and Niskanen, L and Liukkonen, T and Tillonen, J and Kössi, J and Ilvesmäki, V and Viljakka, M and Satokari, R and Arkkila, P}, title = {Effectiveness of Fecal Microbiota Transplantation for Weight Loss in Patients With Obesity Undergoing Bariatric Surgery: A Randomized Clinical Trial.}, journal = {JAMA network open}, volume = {5}, number = {12}, pages = {e2247226}, pmid = {36525272}, issn = {2574-3805}, mesh = {Female ; Humans ; *Obesity, Morbid/surgery ; Fecal Microbiota Transplantation ; Weight Loss ; *Bariatric Surgery ; Obesity/surgery ; }, abstract = {IMPORTANCE: Severe obesity is a major health concern. However, a few patients remain resistant to bariatric surgery and other treatments. Animal studies suggest that weight may be altered by fecal microbiota transplantation (FMT) from a lean donor.<br><br>OBJECTIVE: To determine whether FMT from a lean donor reduces body weight and further improves the results of bariatric surgery.<br><br>This double-blinded, placebo-controlled, multicenter, randomized clinical trial was conducted in 2018 to 2021 among adult individuals with severe obesity treated at 2 bariatric surgery centers in Finland and included 18 months of follow-up. Patients eligible for bariatric surgery were recruited for the study. Data were analyzed from March 2021 to May 2022.<br><br>INTERVENTIONS: FMT from a lean donor or from the patient (autologous placebo) was administered by gastroscopy into the duodenum. Bariatric surgery was performed 6 months after the baseline intervention using laparoscopic Roux-en-Y gastric bypass (LRYGB) or laparoscopic sleeve gastrectomy (LSG).<br><br>MAIN OUTCOMES AND MEASURES: The main outcome was weight reduction measured as the percentage of total weight loss (TWL).<br><br>RESULTS: Forty-one patients were recruited to participate in the study and were included in the final analysis (29 women [71.1%]; mean [SD] age, 48.7 [8.7] years; mean [SD] body mass index, 42.5 [6.0]). A total of 21 patients received FMT from a lean donor, and 20 received an autologous placebo. Six months after FMT, 34 patients underwent LRYGB and 4 underwent LSG. Thirty-four patients (82.9%) attended the last visit 18 months after the baseline visit. The percentage of TWL at 6 months was 4.8% (95% CI, 2.7% to 7.0%; P&#x2009;<&#x2009;.001) in the FMT group and 4.6% (95% CI, 1.5% to 7.6%; P&#x2009;=&#x2009;.006) in the placebo group, but no difference was observed between the groups. At 18 months from the baseline (ie, 12 months after surgery), the percentage of TWL was 25.3% (95% CI, 19.5 to 31.1; P&#x2009;<&#x2009;.001) in the FMT group and 25.2% (95% CI, 20.2 to 30.3; P&#x2009;<&#x2009;.001) in the placebo group; however, no difference was observed between the groups.<br><br>CONCLUSIONS AND RELEVANCE: FMT did not affect presurgical and postsurgical weight loss. Further studies are needed to elucidate the possible role of FMT in obesity.<br><br>TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03391817.}, }
@article {pmid36512373, year = {2023}, author = {Hurley, JC}, title = {Structural equation modelling the impact of antimicrobials on the human microbiome. Colonization resistance versus colonization susceptibility as case studies.}, journal = {The Journal of antimicrobial chemotherapy}, volume = {78}, number = {2}, pages = {328-337}, doi = {10.1093/jac/dkac408}, pmid = {36512373}, issn = {1460-2091}, mesh = {Humans ; Latent Class Analysis ; *Microbiota ; *Anti-Infective Agents/pharmacology ; Bacteria ; }, abstract = {The impact of antimicrobials on the human microbiome and its relationship to human health are of great interest. How antimicrobial exposure might drive change within specific constituents of the microbiome to effect clinically relevant endpoints is difficult to study. Clinical investigation of each step within a network of causation would be challenging if done 'step-by-step'. An analytic tool of great potential to clinical microbiome research is structural equation modelling (SEM), which has a long history of applications to research questions arising within subject areas as diverse as psychology and econometrics. SEM enables postulated models based on a network of causation to be tested en bloc by confrontation with data derived from the literature. Case studies for the potential application of SEM techniques are colonization resistance (CR) and its counterpart, colonization susceptibility (CS), wherein specific microbes within the microbiome are postulated to either impede (CR) or facilitate (CS) invasive infection with pathogenic bacteria. These postulated networks have three causation steps: exposure to specific antimicrobials are key drivers, clinically relevant infection endpoints are the measurable observables and the activity of key microbiome constituents mediating CR or CS, which may be unobservable, appear as latent variables in the model. SEM methods have potential application towards evaluating the activity of specific antimicrobial agents within postulated networks of causation using clinically derived data.}, }
@article {pmid36511710, year = {2023}, author = {Meng, J and Tao, J and Abu, Y and Sussman, DA and Girotra, M and Franceschi, D and Roy, S}, title = {HIV-Positive Patients on Antiretroviral Therapy Have an Altered Mucosal Intestinal but Not Oral Microbiome.}, journal = {Microbiology spectrum}, volume = {11}, number = {1}, pages = {e0247222}, pmid = {36511710}, issn = {2165-0497}, support = {R01 DA044582/DA/NIDA NIH HHS/United States ; }, mesh = {Humans ; *HIV Infections/drug therapy/microbiology ; RNA, Ribosomal, 16S/genetics ; *Microbiota ; *Gastrointestinal Microbiome/genetics ; Intestinal Mucosa/microbiology ; Bacteria/genetics ; }, abstract = {This study characterized compositional and functional shifts in the intestinal and oral microbiome in HIV-positive patients on antiretroviral therapy compared to HIV-negative individuals. Seventy-nine specimens were collected from 5 HIV-positive and 12 control subjects from five locations (colon brush, colon wash, terminal ileum [TI] brush, TI wash, and saliva) during colonoscopy and at patient visits. Microbiome composition was characterized using 16S rRNA sequencing, and microbiome function was predicted using bioinformatics tools (PICRUSt and BugBase). Our analysis indicated that the β-diversity of all intestinal samples (colon brush, colon wash, TI brush, and TI wash) from patients with HIV was significantly different from patients without HIV. Specifically, bacteria from genera Prevotella, Fusobacterium, and Megasphaera were more abundant in samples from HIV-positive patients. On the other hand, bacteria from genera Ruminococcus, Blautia, and Clostridium were more abundant in samples from HIV-negative patients. Additionally, HIV-positive patients had higher abundances of biofilm-forming and pathogenic bacteria. Furthermore, pathways related to translation and nucleotide metabolism were elevated in HIV-positive patients, whereas pathways related to lipid and carbohydrate metabolism were positively correlated with samples from HIV-negative patients. Our analyses further showed variations in microbiome composition in HIV-positive and negative patients by sampling site. Samples from colon wash, colon brush, and TI wash were significant between groups, while samples from TI brush and saliva were not significant. Taken together, here, we report altered intestinal microbiome composition and predicted function in patients with HIV compared to uninfected patients, though we found no changes in the oral microbiome. IMPORTANCE Over 37 million people worldwide are living with HIV. Although the availability of antiretroviral therapy has significantly reduced the number of AIDS-related deaths, individuals living with HIV are at increased risk for opportunistic infections. We now know that HIV interacts with the trillions of bacteria, fungi, and viruses in the human body termed the microbiome. Only a limited number of previous studies have compared variations in the oral and gastrointestinal microbiome with HIV infection. Here, we detail how the oral and gastrointestinal microbiome changes with HIV infection, having used 5 different sampling sites to gain a more comprehensive view of these changes by location. Our results show site-specific changes in the intestinal microbiome associated with HIV infection. Additionally, we show that while there were significant changes in the intestinal microbiome, there were no significant changes in the oral microbiome.}, }
@article {pmid36509925, year = {2023}, author = {Peng, G and Sinkko, HM and Alenius, H and Lozano, N and Kostarelos, K and Bräutigam, L and Fadeel, B}, title = {Graphene oxide elicits microbiome-dependent type 2 immune responses via the aryl hydrocarbon receptor.}, journal = {Nature nanotechnology}, volume = {18}, number = {1}, pages = {42-48}, pmid = {36509925}, issn = {1748-3395}, support = {/WT_/Wellcome Trust/United Kingdom ; }, mesh = {Animals ; *Receptors, Aryl Hydrocarbon/genetics/metabolism ; Zebrafish/metabolism ; Zebrafish Proteins/genetics/metabolism ; Immunity, Innate ; Lymphocytes/metabolism ; *Microbiota ; }, abstract = {The gut microbiome produces metabolites that interact with the aryl hydrocarbon receptor (AhR), a key regulator of immune homoeostasis in the gut[1,2]. Here we show that oral exposure to graphene oxide (GO) modulates the composition of the gut microbiome in adult zebrafish, with significant differences in wild-type versus ahr2-deficient animals. Furthermore, GO was found to elicit AhR-dependent induction of cyp1a and homing of lck[+] cells to the gut in germ-free zebrafish larvae when combined with the short-chain fatty acid butyrate. To obtain further insights into the immune responses to GO, we used single-cell RNA sequencing to profile cells from whole germ-free embryos as well as cells enriched for lck. These studies provided evidence for the existence of innate lymphoid cell (ILC)-like cells[3] in germ-free zebrafish. Moreover, GO endowed with a 'corona' of microbial butyrate triggered the induction of ILC2-like cells with attributes of regulatory cells. Taken together, this study shows that a nanomaterial can influence the crosstalk between the microbiome and immune system in an AhR-dependent manner.}, }
@article {pmid36509338, year = {2023}, author = {Guimarães, VHD and Marinho, BM and Motta-Santos, D and Mendes, GDRL and Santos, SHS}, title = {Nutritional implications in the mechanistic link between the intestinal microbiome, renin-angiotensin system, and the development of obesity and metabolic syndrome.}, journal = {The Journal of nutritional biochemistry}, volume = {113}, number = {}, pages = {109252}, doi = {10.1016/j.jnutbio.2022.109252}, pmid = {36509338}, issn = {1873-4847}, mesh = {Humans ; *Metabolic Syndrome/metabolism ; *Gastrointestinal Microbiome/physiology ; Renin-Angiotensin System ; Obesity/metabolism ; *Probiotics ; Prebiotics ; }, abstract = {Obesity and metabolic disorders represent a significant global health problem and the gut microbiota plays an important role in modulating systemic homeostasis. Recent evidence shows that microbiota and its signaling pathways may affect the whole metabolism and the Renin-Angiotensin System (RAS), which in turn seems to modify microbiota. The present review aimed to investigate nutritional implications in the mechanistic link between the intestinal microbiome, renin-angiotensin system, and the development of obesity and metabolic syndrome components. A description of metabolic changes was obtained based on relevant scientific literature. The molecular and physiological mechanisms that impact the human microbiome were addressed, including the gut microbiota associated with obesity, diabetes, and hepatic steatosis. The RAS interaction signaling and modulation were analyzed. Strategies including the use of prebiotics, symbiotics, probiotics, and biotechnology may affect the gut microbiota and its impact on human health.}, }
@article {pmid36500264, year = {2022}, author = {Chen, L and Yuan, F and Chen, S and Li, X and Kong, L and Zhang, W}, title = {Potential Role of Host Microbiome in Areca Nut-Associated Carcinogenesis and Addiction.}, journal = {Molecules (Basel, Switzerland)}, volume = {27}, number = {23}, pages = {}, pmid = {36500264}, issn = {1420-3049}, support = {No. 81874329 and 82073945//National Natural Science Foundation of China/ ; B2013-097//Scientific Research Project of Hunan Provincial Health Commission/ ; 2021YFA1301200//National Key R&amp;D Program of China/ ; 2018SK50907//Science and Technology Innovation Program of Hunan Provinc/ ; }, mesh = {Humans ; Areca/adverse effects ; Mastication ; *Behavior, Addictive ; *Microbiota ; Polyphenols ; }, abstract = {Areca nut (AN) is widely consumed all over the world, bringing great harm to human health and economy. Individuals with AN chewing are at high risk of cardiovascular disease and impaired immune system and metabolic system. Despite a growing number of studies having reported on the adverse effects brought by AN chewing, the exact mechanism of it is limited and the need for additional exploration remains. In recent years, the interaction between microorganisms, especially intestinal microorganism and host, has been extensively studied. AN chewing might disrupt the oral and intestinal microbiota communities through direct connect with the microbes it contains, altering PH, oxygen of oral and intestinal microenvironment, and disturbing the immune homeostasis. These mechanisms provide insights into the interplay between areca nut and host microbiota. Emerging studies have proposed that bidirectional interaction between polyphenols and intestinal microbes might play a potential role in the divergence of polyphenol, extracted from AN, among individuals with or without AN-induced cancer development and progression. Although some AN chewers have been aware of the harmful effects brought by AN, they cannot abolish this habit because of the addiction of AN. Increasing studies have tried to revealed that gut microbiota might influence the onset/development of addictive behaviors. Altogether, this review summarizes the possible reasons for the disturbance of host microbiota caused by areca nut chewing and clarifies the complex interaction between human microbiome and major constituents and the addiction and carcinogenicity of AN, tempting to provide novel insights into the development and utilization of it, and to control the adverse consequences caused by AN chewing.}, }
@article {pmid36498975, year = {2022}, author = {Del Chierico, F and Rapini, N and Deodati, A and Matteoli, MC and Cianfarani, S and Putignani, L}, title = {Pathophysiology of Type 1 Diabetes and Gut Microbiota Role.}, journal = {International journal of molecular sciences}, volume = {23}, number = {23}, pages = {}, pmid = {36498975}, issn = {1422-0067}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Diabetes Mellitus, Type 1/genetics ; Dysbiosis ; *Microbiota ; *Islets of Langerhans ; }, abstract = {Type 1 diabetes (T1D) is a multifactorial autoimmune disease driven by T-cells against the insulin-producing islet β-cells, resulting in a marked loss of β-cell mass and function. Although a genetic predisposal increases susceptibility, the role of epigenetic and environmental factors seems to be much more significant. A dysbiotic gut microbial profile has been associated with T1D patients. Moreover, new evidence propose that perturbation in gut microbiota may influence the T1D onset and progression. One of the prominent features in clinically silent phase before the onset of T1D is the presence of a microbiota characterized by low numbers of commensals butyrate producers, thus negatively influencing the gut permeability. The loss of gut permeability leads to the translocation of microbes and microbial metabolites and could lead to the activation of immune cells. Moreover, microbiota-based therapies to slow down disease progression or reverse T1D have shown promising results. Starting from this evidence, the correction of dysbiosis in early life of genetically susceptible individuals could help in promoting immune tolerance and thus in reducing the autoantibodies production. This review summarizes the associations between gut microbiota and T1D for future therapeutic perspectives and other exciting areas of research.}, }
@article {pmid36478853, year = {2022}, author = {Peters, SL and Morowitz, MJ and Hettich, RL}, title = {Antibiotic resistance and host immune system-induced metal bactericidal control are key factors for microbial persistence in the developing human preterm infant gut microbiome.}, journal = {Frontiers in microbiology}, volume = {13}, number = {}, pages = {958638}, pmid = {36478853}, issn = {1664-302X}, abstract = {The human gut microbiome, which develops and stabilizes during the early stages of infant life, plays an essential role in host health through the production of metabolic resources and the stimulation and training of the immune system. To study colonization and community functional dynamics of the microbiota based on responses to host immune processes during the normal and dysbiotic establishment of the gut, metaproteomics was conducted on 91 fecal samples collected over the first 90 days of life from 17 hospitalized premature infants. Microbial responses to antibiotic administration and host-imposed metal bactericidal control correlated with community assembly and resiliency of microbes in the developing preterm gut. Specifically, proteins related to antibiotic resistance and metal homeostasis mechanisms were predominant in persisting members in the infant gut environment over the first several weeks of life. Overall, this metaproteomics study provides a unique approach to examine the temporal expansion and resilience of microbial colonization, as it allows simultaneous examination of both host and microbial metabolic activities. Understanding the interplay between host and microbes may elucidate the microbiome's potential immunomodulatory roles relevant to necrotizing enterocolitis and other dysbiotic conditions in preterm infants.}, }
@article {pmid36476670, year = {2022}, author = {Jochum, M and Lee, MD and Curry, K and Zaksas, V and Vitalis, E and Treangen, T and Aagaard, K and Ternus, KL}, title = {Analysis of bronchoalveolar lavage fluid metatranscriptomes among patients with COVID-19 disease.}, journal = {Scientific reports}, volume = {12}, number = {1}, pages = {21125}, pmid = {36476670}, issn = {2045-2322}, support = {P01 AI152999/AI/NIAID NIH HHS/United States ; T32 HD098068/HD/NICHD NIH HHS/United States ; T32 HL098069/HL/NHLBI NIH HHS/United States ; }, mesh = {Humans ; Bronchoalveolar Lavage Fluid ; *COVID-19 ; Gene Ontology ; }, abstract = {To better understand the potential relationship between COVID-19 disease and hologenome microbial community dynamics and functional profiles, we conducted a multivariate taxonomic and functional microbiome comparison of publicly available human bronchoalveolar lavage fluid (BALF) metatranscriptome samples amongst COVID-19 (n = 32), community acquired pneumonia (CAP) (n = 25), and uninfected samples (n = 29). We then performed a stratified analysis based on mortality amongst the COVID-19 cohort with known outcomes of deceased (n = 10) versus survived (n = 15). Our overarching hypothesis was that there are detectable and functionally significant relationships between BALF microbial metatranscriptomes and the severity of COVID-19 disease onset and progression. We observed 34 functionally discriminant gene ontology (GO) terms in COVID-19 disease compared to the CAP and uninfected cohorts, and 21 GO terms functionally discriminant to COVID-19 mortality (q < 0.05). GO terms enriched in the COVID-19 disease cohort included hydrolase activity, and significant GO terms under the parental terms of biological regulation, viral process, and interspecies interaction between organisms. Notable GO terms associated with COVID-19 mortality included nucleobase-containing compound biosynthetic process, organonitrogen compound catabolic process, pyrimidine-containing compound biosynthetic process, and DNA recombination, RNA binding, magnesium and zinc ion binding, oxidoreductase activity, and endopeptidase activity. A Dirichlet multinomial mixtures clustering analysis resulted in a best model fit using three distinct clusters that were significantly associated with COVID-19 disease and mortality. We additionally observed discriminant taxonomic differences associated with COVID-19 disease and mortality in the genus Sphingomonas, belonging to the Sphingomonadacae family, Variovorax, belonging to the Comamonadaceae family, and in the class Bacteroidia, belonging to the order Bacteroidales. To our knowledge, this is the first study to evaluate significant differences in taxonomic and functional signatures between BALF metatranscriptomes from COVID-19, CAP, and uninfected cohorts, as well as associating these taxa and microbial gene functions with COVID-19 mortality. Collectively, while this data does not speak to causality nor directionality of the association, it does demonstrate a significant relationship between the human microbiome and COVID-19. The results from this study have rendered testable hypotheses that warrant further investigation to better understand the causality and directionality of host-microbiome-pathogen interactions.}, }
@article {pmid36475896, year = {2023}, author = {Kumar, T and Bryant, M and Cantrell, K and Song, SJ and McDonald, D and Tubb, HM and Farmer, S and Lukacz, ES and Brubaker, L and Knight, R}, title = {Effects of Variation in Urine Sample Storage Conditions on 16S Urogenital Microbiome Analyses.}, journal = {mSystems}, volume = {8}, number = {1}, pages = {e0102922}, pmid = {36475896}, issn = {2379-5077}, support = {T32 GM007198/GM/NIGMS NIH HHS/United States ; }, mesh = {Adult ; Female ; Humans ; United States ; RNA, Ribosomal, 16S/genetics ; Reproducibility of Results ; Quality of Life ; *Microbiota/genetics ; Urine Specimen Collection ; *Urinary Tract Infections ; *Urinary Incontinence ; }, abstract = {Replicability is a well-established challenge in microbiome research with a variety of contributing factors at all stages, from sample collection to code execution. Here, we focus on voided urine sample storage conditions for urogenital microbiome analysis. Using urine samples collected from 10 adult females, we investigated the microbiome preservation efficacy of AssayAssure Genelock (Genelock), compared with no preservative, under different temperature conditions. We varied temperature over 48 h in order to examine the impact of conditions samples may experience with home voided urine collection and shipping to a central biorepository. The following common lab and shipping conditions were investigated: -20°C, ambient temperature, 4°C, freeze-thaw cycle, and heat cycle. At 48 h, all samples were stored at -80°C until processing. After generating 16S rRNA gene amplicon sequencing data using the highly sensitive KatharoSeq protocol, we observed individual variation in both alpha and beta diversity metrics below interhuman differences, corroborating reports of individual microbiome variability in other specimen types. While there was no significant difference in beta diversity when comparing Genelock versus no preservative, we did observe a higher concordance with Genelock samples shipped at colder temperatures (-20°C and 4°C) when compared with the samples shipped at -20°C without preservative. Our results indicate that Genelock does not introduce a significant amount of microbial bias when used on a range of temperatures and is most effective at colder temperatures. IMPORTANCE The urogenital microbiome is an understudied yet important human microbiome niche. Research has been stimulated by the relatively recent discovery that urine is not sterile; urinary tract microbes have been linked to health problems, including urinary infections, incontinence, and cancer. The quality of life and economic impact of UTIs and urgency incontinence alone are enormous, with $3.5 billion and $82.6 billion, respectively, spent in the United States. annually. Given the low biomass of urine, novelty of the field, and limited reproducibility evidence, it is critical to study urine sample storage conditions to optimize scientific rigor. Efficient and reliable preservation methods inform methods for home self-sample collection and shipping, increasing the potential use in larger-scale studies. Here, we examined both buffer and temperature variation effects on 16S rRNA gene amplicon sequencing results from urogenital samples, providing data on the consequences of common storage methods on urogenital microbiome results.}, }
@article {pmid36475759, year = {2023}, author = {Chen, BY and Lin, WZ and Li, YL and Bi, C and Du, LJ and Liu, Y and Zhou, LJ and Liu, T and Xu, S and Shi, CJ and Zhu, H and Wang, YL and Sun, JY and Liu, Y and Zhang, WC and Zhang, Z and Zhang, HL and Zhu, YQ and Duan, SZ}, title = {Characteristics and Correlations of the Oral and Gut Fungal Microbiome with Hypertension.}, journal = {Microbiology spectrum}, volume = {11}, number = {1}, pages = {e0195622}, pmid = {36475759}, issn = {2165-0497}, mesh = {Humans ; *Mycobiome ; *Gastrointestinal Microbiome/physiology ; *Microbiota ; *Hypertension ; Mouth ; Feces/microbiology ; Fungi/genetics ; }, abstract = {The mycobiome is an essential constituent of the human microbiome and is associated with various diseases. However, the role of oral and gut fungi in hypertension (HTN) remains largely unexplored. In this study, saliva, subgingival plaques, and feces were collected from 36 participants with HTN and 24 healthy controls for metagenomic sequencing. The obtained sequences were analyzed using the Kraken2 taxonomic annotation pipeline to assess fungal composition and diversity. Correlations between oral and gut fungi and clinic parameters, between fungi within the same sample types, and between different sample types were identified by Spearman's correlation analysis. Overall, the subgingival fungal microbiome had substantially higher alpha diversity than the salivary and fecal fungal microbiomes. The fungal microbiomes of the three sample types displayed distinct beta diversity from each other. Oral fungi but not gut fungi in HTN had beta diversity significantly different from that of controls. Among the fungi shared in the oral cavity and gut, Exophiala was the genus with the most notable changes. Exophiala spinifera was the most abundant salivary species in HTN. Some fungal species directly correlated with blood pressure, including gut Exophiala xenobiotica and Exophiala mesophila. The markedly impaired ecological cocorrelation networks of oral and gut fungi in HTN suggested compromised association among fungal species. Most fungi were shared in the oral cavity and gut, and their correlations suggested the potential interplays between oral and gut fungi. In conclusion, the oral cavity and intestine have unique fungal ecological environments. The fungal enrichment and ecology in HTN, the correlations between oral and gut fungi, and the associations between oral and gut fungi and clinical parameters suggest an important role that the fungal microbiome may play in HTN. IMPORTANCE Our study fills the gap in human studies investigating the oral and gut fungal microbiota in association with blood pressure. It characterizes the diversity and composition of the oral and gut fungal microbiome in human subjects, elucidates the dysbiosis of fungal ecology in a hypertensive population, and establishes oral-gut fungal correlations and fungus-clinical parameter correlations. Targeting fungi in the oral cavity and/or gut may provide novel strategies for the prevention and treatment of hypertension.}, }
@article {pmid36475017, year = {2022}, author = {Khan, AZ and Badar, S and O'Callaghan, KM and Zlotkin, S and Roth, DE}, title = {Fecal Iron Measurement in Studies of the Human Intestinal Microbiome.}, journal = {Current developments in nutrition}, volume = {6}, number = {10}, pages = {nzac143}, pmid = {36475017}, issn = {2475-2991}, abstract = {Iron is an essential micronutrient for humans and their intestinal microbiota. Host intestinal cells and iron-dependent bacteria compete for intraluminal iron, so the composition and functions of the gut microbiota may influence iron availability. Studies of the effects of the microbiota or probiotic interventions on host iron absorption may be particularly relevant to settings with high burdens of iron deficiency and gastrointestinal infections, since inflammation reduces iron bioavailability and unabsorbed intraluminal iron may modify the composition of the microbiota. The quantification of stool iron content may serve as an indicator of the amount of intraluminal iron to which the intestinal microbiota is exposed, which is particularly relevant for studies of the effect of iron on the intestinal microbiome, where fecal samples collected for purposes of microbiome characterization can be leveraged for stool iron analysis. However, few studies are available to guide researchers in the selection and implementation of stool iron assays, particularly because cross-comparison of available methods is limited in literature. This review aims to describe the available stool iron quantification methods and highlight their potential application in studies of iron-microbiome relationships, with a focus on pediatric research. MS-based methods offer high sensitivity and precision, but the need for expensive equipment and the high per-sample and maintenance costs may limit their widespread use. Conversely, colorimetric assays offer lower cost, ease of use, and rapid turnaround times but have thus far been optimized primarily for blood-derived matrices rather than stool. Further research efforts are needed to validate and standardize methods for stool iron assessment and to determine if the incorporation of such analyses in human microbiome studies 1) yields insights into the interactions between intestinal microbiota and iron and 2) contributes to the development of interventions that mitigate iron deficiency and promote a healthy microbiome.}, }
@article {pmid36473543, year = {2023}, author = {Li, C}, title = {Understanding interactions among diet, host and gut microbiota for personalized nutrition.}, journal = {Life sciences}, volume = {312}, number = {}, pages = {121265}, doi = {10.1016/j.lfs.2022.121265}, pmid = {36473543}, issn = {1879-0631}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; Diet ; *Microbiota ; Host Microbial Interactions ; }, abstract = {Human responses to the same diets may vary to a large extent, depending on the complex diet-host-microbiota interactions. Recent scientific advance has indicated that this diet-host-microbiota interaction could be quantified to develop strategies for improving individual health (personalized nutrition). Compared to the host related factors (which are difficult to manipulate), the gut microbiome is more readily modulated by dietary exposures and has important roles in affecting human health via the synthesis of various bioactive compounds and participating in the digestion and absorption process of macro- and micronutrients. Therefore, gut microbiota alterations induced by diets could possibly be utilized to improve human health in a targeted manner. However, limitations in the processing and analysis of 'big-data' concerning human microbiome still restrict the translational capacity of diet-host-microbiota interactions into tools to improve personalized human health. In the current review, recent advances in terms of understanding the specific diet-host-microbiota interactions were summarized, aiming to help the development of strategies for personalized nutrition.}, }
@article {pmid36468852, year = {2022}, author = {Velez-Cortes, F and Wang, H}, title = {Characterization and Spatial Mapping of the Human Gut Metasecretome.}, journal = {mSystems}, volume = {7}, number = {6}, pages = {e0071722}, pmid = {36468852}, issn = {2379-5077}, support = {R01 AI132403/AI/NIAID NIH HHS/United States ; R01 DK118044/DK/NIDDK NIH HHS/United States ; R21 AI146817/AI/NIAID NIH HHS/United States ; }, mesh = {Humans ; Bacteria/genetics ; Bacterial Proteins/genetics ; *Gastrointestinal Microbiome/genetics ; Metagenome ; Phylogeny ; }, abstract = {Bacterially secreted proteins play an important role in microbial physiology and ecology in many environments, including the mammalian gut. While gut microbes have been extensively studied over the past decades, little is known about the proteins that they secrete into the gastrointestinal tract. In this study, we developed and applied a computational pipeline to a comprehensive catalog of human-associated metagenome-assembled genomes in order to predict and analyze the bacterial metasecretome of the human gut, i.e., the collection of proteins secreted out of the cytoplasm by human gut bacteria. We identified the presence of large and diverse families of secreted carbohydrate-active enzymes and assessed their phylogenetic distributions across different taxonomic groups, which revealed an enrichment in Bacteroidetes and Verrucomicrobia. By mapping secreted proteins to available metagenomic data from endoscopic sampling of the human gastrointestinal tract, we specifically pinpointed regions in the upper and lower intestinal tract along the lumen and mucosa where specific glycosidases are secreted by resident microbes. The metasecretome analyzed in this study constitutes the most comprehensive list of secreted proteins produced by human gut bacteria reported to date and serves as a useful resource for the microbiome research community. IMPORTANCE Bacterially secreted proteins are necessary for the proper functioning of bacterial cells and communities. Secreted proteins provide bacterial cells with the ability to harvest resources from the exterior, import these resources into the cell, and signal to other bacteria. In the human gut microbiome, these actions impact host health and allow the maintenance of a healthy gut bacterial community. We utilized computational tools to identify the major components of human gut bacterially secreted proteins and determined their spatial distribution in the gastrointestinal tract. Our analysis of human gut bacterial secreted proteins will allow a better understanding of the impact of gut bacteria on human health and represents a step toward identifying new protein functions with interesting applications in biomedicine and industry.}, }
@article {pmid36464584, year = {2023}, author = {Villemin, C and Six, A and Neville, BA and Lawley, TD and Robinson, MJ and Bakdash, G}, title = {The heightened importance of the microbiome in cancer immunotherapy.}, journal = {Trends in immunology}, volume = {44}, number = {1}, pages = {44-59}, doi = {10.1016/j.it.2022.11.002}, pmid = {36464584}, issn = {1471-4981}, mesh = {Humans ; *Microbiota ; *Neoplasms/therapy/microbiology ; Immunotherapy ; Bacteria ; }, abstract = {The human microbiome is recognized as a key factor in health and disease. This has been further corroborated by identifying changes in microbiome composition and function as a novel hallmark in cancer. These effects are exerted through microbiome interactions with host cells, impacting a wide variety of developmental and physiological processes. In this review, we discuss some of the latest findings on how the bacterial component of the microbiome can influence outcomes for different cancer immunotherapy modalities, highlighting identified mechanisms of action. We also address the clinical efforts to utilize this knowledge to achieve better responses to immunotherapy. A refined understanding of microbiome variations in patients and microbiome-host interactions with cancer therapies is essential to realize optimal clinical responses.}, }
@article {pmid36461079, year = {2022}, author = {Verkola, M and Takala, M and Nykäsenoja, S and Olkkola, S and Kurittu, P and Kiljunen, S and Tuomala, H and Järvinen, A and Heikinheimo, A}, title = {Low-level colonization of methicillin-resistant Staphylococcus aureus in pigs is maintained by slowly evolving, closely related strains in Finnish pig farms.}, journal = {Acta veterinaria Scandinavica}, volume = {64}, number = {1}, pages = {34}, pmid = {36461079}, issn = {1751-0147}, support = {304832//Academy of Finland/ ; }, mesh = {Swine ; Animals ; Farms ; *Methicillin-Resistant Staphylococcus aureus/genetics ; Finland/epidemiology ; Livestock ; Skin ; }, abstract = {BACKGROUND: Over the past two decades, livestock-associated methicillin-resistant Staphylococcus aureus (LA-MRSA) has become widely prevalent in pig production in Europe. The carriage status of LA-MRSA is known to vary among individual pigs, but bacterial load in pigs has rarely been studied. We assessed the quantity of LA-MRSA in nasal and skin samples of pigs and investigated the genetic diversity of the strains together with sequenced strains from national surveillance and pathology samples from the Finnish Food Authority. On two farms with assumed MRSA-positive status, farm 1 and farm 2, 10 healthy pigs were sampled three times during 2 weeks from the nares and skin (study A). On farm 1, 54 additional pigs were sampled and from confirmed MRSA-positive animals, 10 were randomly selected and transported to a clean, controlled environment for further sampling (study B). From the samples taken on farms 1 and 2 and in the controlled environment, MRSA was isolated both by direct plating and enrichment on selective media. spa types, multilocus sequence types, staphylococcal cassette chromosome mec types, resistance and virulence genes were determined. Core genome multilocus sequence typing (cgMLST) analysis was performed, including the sequences deriving from the surveillance/pathology samples from the Finnish Food Authority.<br><br>RESULTS: All pigs on farm&#xa0;1 carried LA-MRSA in the nares at all three time points and five pigs on farm&#xa0;2 at one time point. Nasal quantity varied between 10 and 10[3]&#xa0;CFU/swab and quantity on the skin between 10 and 10[2]&#xa0;CFU/swab. In the controlled environment, MRSA was detected in at least one of the nasal samples from each animal. spa type t034 was predominant. cgMLST showed one cluster with minimum allele differences between 0 and 11.<br><br>CONCLUSIONS: The study shows predominantly low-level carriage (<&#x2009;10[3]&#xa0;CFU/swab) of LA-MRSA on farms. In the controlled environment we observed a decline in nasal carriage but constant skin carriage. cgMLST showed that strains of spa type t034 are closely related at the national level.}, }
@article {pmid36460704, year = {2022}, author = {Kim, HS and Kim, DW and Kim, S and Choe, S}, title = {Biochemical characterization of the two novel mgCas12a proteins from the human gut metagenome.}, journal = {Scientific reports}, volume = {12}, number = {1}, pages = {20857}, pmid = {36460704}, issn = {2045-2322}, mesh = {Humans ; *Metagenome ; Amino Acid Sequence ; *Endonucleases ; Biological Assay ; Biotechnology ; }, abstract = {CRISPR/Cas9 and Cas12a belonging to the Class II CRISPR system are characterized by a single-component effector protein. Despite unique features of Cas12a like DNA cleavage with 5' staggered ends and a single crRNA, Cas12a has not been adopted in biotechnological applications to the similar extent as Cas9. To better understand the CRISPR/Cas12 systems, we selected two candidates, designated mgCas12a-1 and mgCas12a-2, from an analysis of the human microbiome metagenome (mg) and provided biochemical characterization. These new Cas12a proteins shared about 37% identity in amino acid sequences and shared the same direct repeat sequences in the crRNA with FnCas12a from Francisella novicida. The purification yield of the recombinant proteins was up to 3.6-fold greater than that of FnCas12a. In cell-free DNA cleavage assays, both mgCas12a proteins showed the higher cleavage efficiencies when Mn[2+] was provided with KCl (< 100 mM) than tested other divalent ions. They were able to tolerate ranges of pH points and temperature, and showed the highest cleavage efficiencies at pH 8.0 and 50 °C. In addition, mgCas12a proteins showed 51% less crRNA-independent and 56% less crRNA-dependent non-specific nuclease activity upon prolonged incubation than did FnCas12a. Considering their greater yield in protein preparation and reduced non-specific nuclease activity, our findings may expedite the use of Cas12a especially when genome editing needs to be practiced with the form of ribonucleoproteins.}, }
@article {pmid36458216, year = {2022}, author = {Kalia, VC and Gong, C and Shanmugam, R and Lee, JK}, title = {Prospecting Microbial Genomes for Biomolecules and Their Applications.}, journal = {Indian journal of microbiology}, volume = {62}, number = {4}, pages = {516-523}, pmid = {36458216}, issn = {0046-8991}, abstract = {Bioactive molecules of microbial origin are finding increasing biotechnological applications. Their sources range from the terrestrial, marine, and endophytic to the human microbiome. These biomolecules have unique chemical structures and related groups, which enable them to improve the efficiency of the bioprocesses. This review focuses on the applications of biomolecules in bioremediation, agriculture, food, pharmaceutical industries, and human health.}, }
@article {pmid36458093, year = {2022}, author = {Larsen, PE and Dai, Y}, title = {Modeling interaction networks between host, diet, and bacteria predicts obesogenesis in a mouse model.}, journal = {Frontiers in molecular biosciences}, volume = {9}, number = {}, pages = {1059094}, pmid = {36458093}, issn = {2296-889X}, abstract = {Host-microbiome interactions are known to have substantial effects on human health, but the diversity of the human microbiome makes it difficult to definitively attribute specific microbiome features to a host phenotype. One approach to overcoming this challenge is to use animal models of host-microbiome interaction, but it must be determined that relevant aspects of host-microbiome interactions are reflected in the animal model. One such experimental validation is an experiment by Ridura et al. In that experiment, transplanting a microbiome from a human into a mouse also conferred the human donor's obesity phenotype. We have aggregated a collection of previously published host-microbiome mouse-model experiments and combined it with thousands of sequenced and annotated bacterial genomes and metametabolomic pathways. Three computational models were generated, each model reflecting an aspect of host-microbiome interactions: 1) Predict the change in microbiome community structure in response to host diet using a community interaction network, 2) Predict metagenomic data from microbiome community structure, and 3) Predict host obesogenesis from modeled microbiome metagenomic data. These computationally validated models were combined into an integrated model of host-microbiome-diet interactions and used to replicate the Ridura experiment in silico. The results of the computational models indicate that network-based models are significantly more predictive than similar but non-network-based models. Network-based models also provide additional insight into the molecular mechanisms of host-microbiome interaction by highlighting metabolites and metabolic pathways proposed to be associated with microbiome-based obesogenesis. While the models generated in this study are likely too specific to the animal models and experimental conditions used to train our models to be of general utility in a broader understanding of obesogenesis, the approach detailed here is expected to be a powerful tool of investigating multiple types of host-microbiome interactions.}, }
@article {pmid36457513, year = {2022}, author = {Liu, B and Li, Y and Suo, L and Zhang, W and Cao, H and Wang, R and Luan, J and Yu, X and Dong, L and Wang, W and Xu, S and Lu, S and Shi, M}, title = {Characterizing microbiota and metabolomics analysis to identify candidate biomarkers in lung cancer.}, journal = {Frontiers in oncology}, volume = {12}, number = {}, pages = {1058436}, pmid = {36457513}, issn = {2234-943X}, abstract = {BACKGROUND: Lung cancer is the leading malignant disease and cause of cancer-related death worldwide. Most patients with lung cancer had insignificant early symptoms so that most of them were diagnosed at an advanced stage. In addition to factors such as smoking, pollution, lung microbiome and its metabolites play vital roles in the development of lung cancer. However, the interaction between lung microbiota and carcinogenesis is lack of systematically characterized and controversial. Therefore, the purpose of this study was to excavate the features of the lung microbiota and metabolites in patients and verify potential biomarkers for lung cancer diagnosis.<br><br>METHODS: Lung tissue flushing solutions and bronchoalveolar lavage fluid samples came from patients with lung cancer and non-lung cancer. The composition and variations of the microbiota and metabolites in samples were explored using muti-omics technologies including 16S rRNA amplicon sequencing, metagenomics and metabolomics.<br><br>RESULTS: The metabolomics analysis indicated that 40 different metabolites, such as 9,10-DHOME, sphingosine, and cysteinyl-valine, were statistically significant between two groups (VIP > 1 and P < 0.05). These metabolites were significantly enriched into 11 signal pathways including sphingolipid, autophagy and apoptosis signaling pathway (P < 0.05). The analysis of lung microbiota showed that significant changes reflected the decrease of microbial diversity, changes of distribution of microbial taxa, and variability of the correlation networks of lung microbiota in lung cancer patients. In particular, we found that oral commensal microbiota and multiple probiotics might be connected with the occurrence and progression of lung cancer. Moreover, our study found 3 metabolites and 9 species with significantly differences, which might be regarded as the potential clinical diagnostic markers associated with lung cancer.<br><br>CONCLUSIONS: Lung microbiota and metabolites might play important roles in the pathogenesis of lung cancer, and the altered metabolites and microbiota might have the potential to be clinical diagnostic markers and therapeutic targets associated with lung cancer.}, }
@article {pmid36453887, year = {2022}, author = {Zhang, W and Han, N and Zhang, T and Qiang, Y and Peng, X and Li, X and Kan, B}, title = {The Spatial Features and Temporal Changes in the Gut Microbiota of a Healthy Chinese Population.}, journal = {Microbiology spectrum}, volume = {10}, number = {6}, pages = {e0131022}, pmid = {36453887}, issn = {2165-0497}, mesh = {Adult ; Humans ; *Gastrointestinal Microbiome/genetics ; RNA, Ribosomal, 16S/genetics ; Cohort Studies ; East Asian People ; *Microbiota ; Feces/microbiology ; }, abstract = {In this study, we aimed to understand the characteristics of the gut microbial composition in a healthy Chinese population and to evaluate if they differed across different regions. In addition, we aimed to understand the changes in the gut microbial composition over time. We collected 239 fecal samples from healthy Chinese adults living in four regions and performed a 1-year time cohort study in a small population in Beijing. The Chinese gut microbiota share 34 core bacterial genera and 39 core bacterial species, which exist in all collected samples. Several disease-related microorganisms (DRMs), virulence factors, and antibiotic resistance genes were found in one or more healthy Chinese samples. Differences in gut microbiota were observed in samples from different regions, locations, individuals, and time points. Compared to other factors, time was associated with a lower degree of change in the gut microbiota. Our findings revealed spatial and temporal changes in the gut microbiota of healthy Chinese individuals. Compared to fecal microbiomes of 152 samples in the publicly released the Human Microbiome Project (HMP) project from the United States, samples in this study have higher variability in the fecal microbiome, with higher richness, Shannon diversity indices, and Pielou evenness indexes, at both the genus and species levels. The microbiota data obtained in this study will provide a detailed basis for further understanding the composition of the gut microbiota in the healthy Chinese population. IMPORTANCE China accounts for approximately 1/5th of the world's total population. Differences in environment, ethnicity, and living habits could impart unique features to the structure of the gut microbiota of Chinese individuals. In 2016, we started to investigate healthy Chinese people and their gut microbiomes. Phase I results for 16S rRNA amplicons have been released. However, owing to the limitations of 16S rRNA amplicon sequencing, the gut microbiome of a healthy Chinese population could not be examined thoroughly at the species level, and the detailed changes in the gut microbiota over time need to be investigated. To address these knowledge gaps, we started a phase II study and investigated the basis for variations in the gut microbiome composition in a healthy Chinese population at the species level using shotgun metagenomics technology. In the phase II study, we also conducted a time scale analysis of fecal samples from healthy Chinese subjects, as a pioneered study, which quantitatively clarified the changes in the gut microbiota at both the spatial and temporal levels and elucidated the distribution pattern of DRMs in healthy Chinese individuals.}, }
@article {pmid36453834, year = {2023}, author = {Ndika, J and Suojalehto, H and Lindström, I and Airaksinen, L and Wisgrill, L and Alenius, H and Karisola, P}, title = {Systemic gene signature of inhaled corticosteroid treatment in allergic asthma to flour.}, journal = {Allergy}, volume = {78}, number = {2}, pages = {592-595}, doi = {10.1111/all.15605}, pmid = {36453834}, issn = {1398-9995}, mesh = {Humans ; *Flour ; *Asthma/drug therapy/genetics ; Adrenal Cortex Hormones/therapeutic use ; Administration, Inhalation ; }, }
@article {pmid36452234, year = {2022}, author = {Wang, Z and Li, L and Wang, S and Wei, J and Qu, L and Pan, L and Xu, K}, title = {The role of the gut microbiota and probiotics associated with microbial metabolisms in cancer prevention and therapy.}, journal = {Frontiers in pharmacology}, volume = {13}, number = {}, pages = {1025860}, pmid = {36452234}, issn = {1663-9812}, abstract = {Cancer is the second leading cause of elevated mortality worldwide. Thus, the development of drugs and treatments is needed to enhance the survival rate of the cancer-affected population. Recently, gut microbiota research in the healthy development of the human body has garnered widespread attention. Many reports indicate that changes in the gut microbiota are strongly associated with chronic inflammation-related diseases, including colitis, liver disease, and cancer within the intestine and the extraintestinal tract. Different gut bacteria are vital in the occurrence and development of tumors within the gut and extraintestinal tract. The human gut microbiome has significant implications for human physiology, including metabolism, nutrient absorption, and immune function. Moreover, diet and lifestyle habits are involved in the evolution of the human microbiome throughout the lifetime of the host and are involved in drug metabolism. Probiotics are a functional food with a protective role in cancer development in animal models. Probiotics alter the gut microbiota in the host; thus, beneficial bacterial activity is stimulated, and detrimental activity is inhibited. Clinical applications have revealed that some probiotic strains could reduce the occurrence of postoperative inflammation among cancer patients. An association network was constructed by analyzing the previous literature to explore the role of probiotics from the anti-tumor perspective. Therefore, it provides direction and insights for research on tumor treatment.}, }
@article {pmid36448728, year = {2022}, author = {Paone, P and Suriano, F and Jian, C and Korpela, K and Delzenne, NM and Van Hul, M and Salonen, A and Cani, PD}, title = {Prebiotic oligofructose protects against high-fat diet-induced obesity by changing the gut microbiota, intestinal mucus production, glycosylation and secretion.}, journal = {Gut microbes}, volume = {14}, number = {1}, pages = {2152307}, pmid = {36448728}, issn = {1949-0984}, mesh = {Mice ; Animals ; Prebiotics ; Diet, High-Fat/adverse effects ; *Gastrointestinal Microbiome ; Glycosylation ; *Diabetes Mellitus, Type 2 ; Obesity/prevention &amp; control ; Bacteroidetes ; Mucus ; }, abstract = {Obesity is a major risk factor for the development of type 2 diabetes and cardiovascular diseases, and gut microbiota plays a key role in influencing the host energy homeostasis. Moreover, obese mice have a different gut microbiota composition, associated with an alteration of the intestinal mucus layer, which represents the interface between the bacteria and the host. We previously demonstrated that prebiotic treatment with oligofructose (FOS) counteracted the effects of diet-induced obesity, together with changes in the gut microbiota composition, but it is not known if the intestinal mucus layer could be involved. In this study, we found that, in addition to preventing high-fat diet (HFD) induced obesity in mice, the treatment with FOS increased the expression of numerous genes involved in mucus production, glycosylation and secretion, the expression of both secreted and transmembrane mucins, and the differentiation and number of goblet cells. These results were associated with significant changes in the gut microbiota composition, with FOS significantly increasing the relative and absolute abundance of the bacterial genera Odoribacter, Akkermansia, two unknown Muribaculaceae and an unknown Ruminococcaceae. Interestingly, all these bacterial genera had a negative association with metabolic parameters and a positive association with markers of the mucus layer. Our study shows that FOS treatment is able to prevent HFD-induced metabolic disorders, at least in part, by acting on all the processes of the mucus production. These data suggest that targeting the mucus and the gut microbiota by using prebiotics could help to prevent or mitigate obesity and related disorders.}, }
@article {pmid36444784, year = {2023}, author = {Pereira, MS and Kriegel, MA}, title = {Evolving concepts of host-pathobiont interactions in autoimmunity.}, journal = {Current opinion in immunology}, volume = {80}, number = {}, pages = {102265}, doi = {10.1016/j.coi.2022.102265}, pmid = {36444784}, issn = {1879-0372}, mesh = {Humans ; Autoimmunity ; *Autoimmune Diseases/etiology ; Autoantigens ; *Microbiota ; Mucous Membrane ; }, abstract = {Autoimmune diseases are complex, multifactorial diseases with a polygenic trait and diverse environmental factors that contribute to triggering and exacerbating each disorder. The human microbiome is increasingly implicated in the multistep pathogenesis of autoimmune diseases. We summarize here the latest developments in the field of how the microbiota interacts with the host on a cellular and molecular level. We review how pathobionts evolve within the gut of autoimmune-prone hosts to translocate to secondary lymphoid tissues. On mucosal sites and in non-gut tissues, pathobionts trigger autoimmune pathways through various mechanisms, including cross-reactivity with autoantigens and secretion of metabolites that alter immune functions. A better understanding of these mechanisms will hasten the development of unconventional therapeutic approaches for autoimmune diseases.}, }
@article {pmid36443470, year = {2022}, author = {Jang, H and Koh, H and Gu, W and Kang, B}, title = {Integrative web cloud computing and analytics using MiPair for design-based comparative analysis with paired microbiome data.}, journal = {Scientific reports}, volume = {12}, number = {1}, pages = {20465}, pmid = {36443470}, issn = {2045-2322}, mesh = {Humans ; Cloud Computing ; *Microbiota ; *Gastrointestinal Microbiome ; Mouth ; Skin ; }, abstract = {Pairing (or blocking) is a design technique that is widely used in comparative microbiome studies to efficiently control for the effects of potential confounders (e.g., genetic, environmental, or behavioral factors). Some typical paired (block) designs for human microbiome studies are repeated measures designs that profile each subject's microbiome twice (or more than twice) (1) for pre and post treatments to see the effects of a treatment on microbiome, or (2) for different organs of the body (e.g., gut, mouth, skin) to see the disparity in microbiome between (or across) body sites. Researchers have developed a sheer number of web-based tools for user-friendly microbiome data processing and analytics, though there is no web-based tool currently available for such paired microbiome studies. In this paper, we thus introduce an integrative web-based tool, named MiPair, for design-based comparative analysis with paired microbiome data. MiPair is a user-friendly web cloud service that is built with step-by-step data processing and analytic procedures for comparative analysis between (or across) groups or between baseline and other groups. MiPair employs parametric and non-parametric tests for complete or incomplete block designs to perform comparative analyses with respect to microbial ecology (alpha- and beta-diversity) and taxonomy (e.g., phylum, class, order, family, genus, species). We demonstrate its usage through an example clinical trial on the effects of antibiotics on gut microbiome. MiPair is an open-source software that can be run on our web server (http://mipair.micloud.kr) or on user's computer (https://github.com/yj7599/mipairgit).}, }
@article {pmid36441207, year = {2023}, author = {Wei, Y and Wang, Z and Liu, Y and Liao, B and Zong, Y and Shi, Y and Liao, M and Wang, J and Zhou, X and Cheng, L and Ren, B}, title = {Extracellular vesicles of Candida albicans regulate its own growth through the L-arginine/nitric oxide pathway.}, journal = {Applied microbiology and biotechnology}, volume = {107}, number = {1}, pages = {355-367}, pmid = {36441207}, issn = {1432-0614}, support = {82071106//National Natural Science Foundation of China/ ; 82271033//National Natural Science Foundation of China/ ; 81600858//National Natural Science Foundation of China/ ; 81870778//National Natural Science Foundation of China/ ; 81991500//National Natural Science Foundation of China/ ; 81991501//National Natural Science Foundation of China/ ; 2021YFQ0064//Key Research and Development Projects of Science and Technology Department of Sichuan Province/ ; 2020YJ0227//Applied Basic Research Program of Sichuan Province/ ; 2022-YF05-01401-SN//Technology Innovation R&amp;D Project of Chengdu/ ; RCDWJS2021-19//Research Funding from West China School/Hospital of Stomatology Sichuan University/ ; }, mesh = {Humans ; *Candida albicans ; Nitric Oxide/metabolism ; Reactive Oxygen Species/metabolism ; *Extracellular Vesicles/metabolism ; Arginine/metabolism ; }, abstract = {Candida albicans is the main conditional pathogenic fungus among the human microbiome. Extracellular vesicles (EVs) secreted by C. albicans are important for its pathogenesis. However, the effects and mechanisms of EVs on C. albicans own growth are not clear. Here, we isolated EVs from C. albicans cells grown in four culture media, including RPMI 1640, DMEM, YPD, and YNB, and measured their effects on the own growth of C. albicans in these media. All the C. albicans EVs from the four media could promote the growth of C. albicans in RPMI 1640 and DMEM media, but had no effects in YPD and YNB media, indicating that the effects of EVs on C. albicans growth were dependent on some media contents. By comparing the media contents and transcriptome analysis, arginine was identified as the key factor for the growth promotion of C. albicans EVs. EVs activated the L-arginine/nitric oxide pathway to promote the growth of C. albicans through that EVs increased the NO levels and upregulated the expression of NO dioxygenase gene YHB1 to reduce the intracellular reactive oxygen species (ROS) and cell apoptosis. During the host cell infections, C. albicans EVs synergistically enhanced the destructive effects of C. albicans to host cells, including RAW264.7, HOK, TR146, and HGEC, suggesting that the growth promotion by EVs enhanced the pathogenesis of C. albicans. Our results demonstrated the important roles of EVs on C. albicans own growth for the first time and highlight its synergism with C. albicans to increase the pathogenesis. KEY POINTS: • C. albicans extracellular vesicles (EVs) promoted its own growth. • EVs activated the l-arginine/NO pathway to reduce ROS and apoptosis of C. albicans. • EVs enhanced the damage to the host cell caused by C. albicans.}, }
@article {pmid36438051, year = {2022}, author = {Tong, L and Constancias, F and Hou, A and Chua, SL and Drautz-Moses, DI and Schuster, SC and Yang, L and Williams, RBH and Kjelleberg, S}, title = {Shotgun metagenomic sequencing analysis of ocular surface microbiome in Singapore residents with mild dry eye.}, journal = {Frontiers in medicine}, volume = {9}, number = {}, pages = {1034131}, pmid = {36438051}, issn = {2296-858X}, abstract = {The ocular surface microbiome has implications for ocular surface inflammation and immunology. Previous shotgun metagenomics analyses were performed in China, showing results that differed according to environment and age. Patients with Sjogren's syndrome were reported to have altered conjunctival microbiome, but such studies have not been done in milder dry eye. The aim of this study is to describe the conjunctival microbiome in people with mild dry eye in Singapore. Samples were collected from 14 participants with mild dry eye and 10 age-matched comparison participants recruited from Singapore National Eye Centre (SNEC) clinics. Shotgun metagenomic sequencing analysis was employed to evaluate the conjunctival microbiome composition. Proteobacteria formed the predominant phylum in the conjunctiva. As in a study from a coastal city in China, Achromobacter spp. was numerically most abundant. Compared to age-matched controls, the conjunctival microbial composition in mild dry eye was similar. Several microorganisms, including Streptococcus spp. increased in representation with age, and the abundance of Staphylococcus correlated with Schirmer readings. In addition, when cultured corneal epithelial cells were exposed to three strains of Achromobacter xylosoxidans, cytokines such as TNF-α and IL-6 were upregulated in the cell lysates and supernatants. Ourresults suggest that age is an important factor that affects composition of the conjunctival microbiome, and relative abundance of specific microorganism may vary according to the environment of the human host.}, }
@article {pmid36435302, year = {2023}, author = {Hussain, A and Patwekar, U and Mongad, DS and Shouche, YS}, title = {Strategizing the human microbiome for small molecules: Approaches and perspectives.}, journal = {Drug discovery today}, volume = {28}, number = {2}, pages = {103459}, doi = {10.1016/j.drudis.2022.103459}, pmid = {36435302}, issn = {1878-5832}, mesh = {Humans ; *Microbiota/genetics ; Genomics ; Host Microbial Interactions ; }, abstract = {Studies of the human microbiome are providing a deeper understanding of its significance to human health, and increasing evidence links the microbiota with several diseases. Nevertheless, the exact mechanisms involved in human-microbe interactions are mostly undefined. The genomic potential of the human microbiome to biosynthesize distinct molecules outmatches its known chemical space, and small-molecule discovery in this context remains in its infancy. The profiling of microbiome-derived small molecules and their contextualization through cause-effect mechanistic studies may provide a better understanding of host-microbe interactions, guide new therapeutic interventions, and modulate microbiome-based therapies. This review describes the advances, approaches, and allied challenges in mining new microbial scaffolds from the human microbiome using genomic, microbe cultivation, and chemical analytic platforms. In the future, the complete biological characterization of a single microbe-derived molecule that has a specific therapeutic application could resolve the current limitations of microbiota-modulating therapies.}, }
@article {pmid36432588, year = {2022}, author = {Pino, A and Vaccalluzzo, A and Caggia, C and Balzaretti, S and Vanella, L and Sorrenti, V and Ronkainen, A and Satokari, R and Randazzo, CL}, title = {Lacticaseibacillus rhamnosus CA15 (DSM 33960) as a Candidate Probiotic Strain for Human Health.}, journal = {Nutrients}, volume = {14}, number = {22}, pages = {}, pmid = {36432588}, issn = {2072-6643}, mesh = {Female ; Humans ; Caco-2 Cells ; Antioxidants/pharmacology ; Ecosystem ; Hydrogen Peroxide ; Bacterial Adhesion ; *Lacticaseibacillus rhamnosus ; *Probiotics ; }, abstract = {Lactobacilli with probiotic properties have emerged as promising tools for both the prevention and treatment of vaginal dysbiosis. The present study aimed to study the in vitro probiotic potential of the Lacticaseibacillus rhamnosus CA15 (DSM 33960) strain isolated from a healthy vaginal ecosystem. The strain was evaluated for both functional (antagonistic activity against pathogens; H2O2, organic acid, and lactic acid production; antioxidant and anti-inflammatory activities; ability to adhere to intestinal mucus and to both CaCo-2 and VK7/E6E7 cell lines; exopolysaccharide production; surface properties; and ability to survive during gastrointestinal transit) and safety (hemolytic, DNase, and gelatinase activities; mucin degradation ability; production of biogenic amines; and resistance to antimicrobials) characteristics. Data revealed that the tested strain was able to antagonize a broad spectrum of vaginal pathogens. In addition, the adhesion capacity to both vaginal and intestinal cell lines, as well as anti-inflammatory and antioxidant activities, was detected. The ability of the Lacticaseibacillus rhamnosus CA15 (DSM 33960) strain to survive under harsh environmental conditions occurring during the gastrointestinal passage suggests its possible oral delivery. Thus, in vitro data highlighted interesting probiotic properties of the CA15 (DSM 33960) strain, which could represent a valuable candidate for in vivo vaginal infections treatment.}, }
@article {pmid36430609, year = {2022}, author = {Tilocca, B and Soggiu, A and Iavarone, F and Greco, V and Putignani, L and Ristori, MV and Macari, G and Spina, AA and Morittu, VM and Ceniti, C and Piras, C and Bonizzi, L and Britti, D and Urbani, A and Figeys, D and Roncada, P}, title = {The Functional Characteristics of Goat Cheese Microbiota from a One-Health Perspective.}, journal = {International journal of molecular sciences}, volume = {23}, number = {22}, pages = {}, pmid = {36430609}, issn = {1422-0067}, support = {AIM1879147 - 2 (Bruno Tilocca)//Attraction International Mobility-AIM, PON-FSE/ ; }, mesh = {Animals ; *Cheese/analysis ; Goats/genetics ; RNA, Ribosomal, 16S/genetics ; *One Health ; Bacteria/genetics ; *Microbiota/genetics ; }, abstract = {Goat cheese is an important element of the Mediterranean diet, appreciated for its health-promoting features and unique taste. A pivotal role in the development of these characteristics is attributed to the microbiota and its continuous remodeling over space and time. Nevertheless, no thorough study of the cheese-associated microbiota using two metaomics approaches has previously been conducted. Here, we employed 16S rRNA gene sequencing and metaproteomics to explore the microbiota of a typical raw goat milk cheese at various ripening timepoints and depths of the cheese wheel. The 16S rRNA gene-sequencing and metaproteomics results described a stable microbiota ecology across the selected ripening timepoints, providing evidence for the microbiologically driven fermentation of goat milk products. The important features of the microbiota harbored on the surface and in the core of the cheese mass were highlighted in both compositional and functional terms. We observed the rind microbiota struggling to maintain the biosafety of the cheese through competition mechanisms and/or by preventing the colonization of the cheese by pathobionts of animal or environmental origin. The core microbiota was focused on other biochemical processes, supporting its role in the development of both the health benefits and the pleasant gustatory nuances of goat cheese.}, }
@article {pmid36426891, year = {2022}, author = {Najmanová, L and Vídeňská, P and Cahová, M}, title = {Healthy microbiome - a mere idea or a sound concept?.}, journal = {Physiological research}, volume = {71}, number = {6}, pages = {719-738}, pmid = {36426891}, issn = {1802-9973}, mesh = {Humans ; *Microbiota/physiology ; }, abstract = {Hundreds of studies in last decades have aimed to compare the microbiome of patients suffering from diverse diseases with that of healthy controls. The microbiome-related component was additionally identified in pathophysiology of many diseases formerly considered to depend only on the host physiology. This, however, opens important questions like: "What is the healthy microbiome?" or "Is it possible to define it unequivocally?". In this review, we describe the main hindrances complicating the definition of "healthy microbiome" in terms of microbiota composition. We discuss the human microbiome from the perspective of classical ecology and we advocate for the shift from the stress on microbiota composition to the functions that microbiome ensures for the host. Finally, we propose to leave the concept of ideal healthy microbiome and replace it by focus on microbiome advantageous for the host, which always depends on the specific context like the age, genetics, dietary habits, body site or physiological state.}, }
@article {pmid36426699, year = {2022}, author = {Wang, SS and Song, F and Wei, XW and Gu, HY and Zhang, K and Zhou, YX and Jiang, LR and Luo, HB}, title = {Research Progress on the Application of Human Oral Microbiome in Forensic Individual Identification.}, journal = {Fa yi xue za zhi}, volume = {38}, number = {4}, pages = {526-532}, doi = {10.12116/j.issn.1004-5619.2021.510101}, pmid = {36426699}, issn = {1004-5619}, mesh = {Humans ; *Microbiota ; Forensic Medicine ; }, abstract = {The oral cavity is the second largest microbial bank in humans after the intestinal canal, colonizing a large number of microorganisms including viruses, bacteria, archaea, fungi and protozoa. The great number of microbial cells, good DNA stability, and individual has a unique microbial community, these characteristics make the human microbiome expected to become a new biomarker for forensic individual identification. This article describes the characteristics of human oral microorganisms and microbial molecular markers in detail, analyzes the potential application value of microorganisms in forensic individual identification, and reviews the research progress of human oral microorganisms in forensic individual identification.}, }
@article {pmid36421395, year = {2022}, author = {Silva, DG and Domingues, CPF and Figueiredo, JF and Dionisio, F and Botelho, A and Nogueira, T}, title = {Estuarine Aquacultures at the Crossroads of Animal Production and Antibacterial Resistance: A Metagenomic Approach to the Resistome.}, journal = {Biology}, volume = {11}, number = {11}, pages = {}, pmid = {36421395}, issn = {2079-7737}, support = {ALG-01-0145-FEDER-028824//Funda&#xe7;&#xe3;o para a Ci&#xea;ncia e Tecnologia/ ; UI/BD/153078/2022//Funda&#xe7;&#xe3;o para a Ci&#xea;ncia e Tecnologia/ ; }, abstract = {It is recognized that the spread of antibiotic resistance (AR) genes among aquatic environments, including aquaculture and the human environment, can have detrimental effects on human and animal health and the ecosystem. Thus, when transmitted to the human microbiome or pathogens, resistance genes risk human health by compromising the eventual treatment of infections with antibiotic therapy. This study aimed to define the resistance profile of aquaculture farms and their potential risk for spreading. Twenty-four sediments from oyster and gilthead sea bream aquaculture farms located in three Portuguese river estuaries (17 sediments from Sado, 4 from Aveiro, and 3 from Lima) were studied by comparative metagenomic analysis. The computation of the diversity of genes conferring resistance per antibiotic class revealed a significant increase in aminoglycosides, beta-lactams, disinfectants, quinolones, and tetracyclines counts. In all geographic locations under study, the most diverse AR genes confer resistance to the macrolides, tetracyclines and oxazolidinones classes, all of which are medically important for human and animal therapies, as well as resistance to disinfectants. The diversity of mobile genetic elements correlated with the number of AR genes such as tetracyclines, suggesting that AR could be easily mobilized among bacterial genomes and microbiomes.}, }
@article {pmid36419417, year = {2022}, author = {Hickman, B and Kirjavainen, PV and Täubel, M and de Vos, WM and Salonen, A and Korpela, K}, title = {Determinants of bacterial and fungal microbiota in Finnish home dust: Impact of environmental biodiversity, pets, and occupants.}, journal = {Frontiers in microbiology}, volume = {13}, number = {}, pages = {1011521}, pmid = {36419417}, issn = {1664-302X}, abstract = {The indoors is where many humans spend most of their time, and are strongly exposed to indoor microbiota, which may have multifaceted effects on health. Therefore, a comprehensive understanding of the determinants of indoor microbiota is necessary. We collected dust samples from 295 homes of families with young children in the Helsinki region of Finland and analyzed the bacterial and fungal composition based on the 16S rRNA and ITS DNA sequences. Microbial profiles were combined with extensive survey data on family structure, daily life, and physical characteristics of the home, as well as additional external environmental information, such as land use, and vegetational biodiversity near the home. Using permutational multivariate analysis of variance we explained 18% of the variation of the relative abundance between samples within bacterial composition, and 17% of the fungal composition with the explanatory variables. The fungal community was dominated by the phyla Basidiomycota, and Ascomycota; the bacterial phyla Proteobacteria, Firmicutes, Cyanobacteria, and Actinobacteria were dominant. The presence of dogs, multiple children, and firewood were significantly associated with both the fungal and bacterial composition. Additionally, fungal communities were associated with land use, biodiversity in the area, and the type of building, while bacterial communities were associated with the human inhabitants and cleaning practices. A distinction emerged between members of Ascomycota and Basidiomycota, Ascomycota being more abundant in homes with greater surrounding natural environment, and potential contact with the environment. The results suggest that the fungal composition is strongly dependent on the transport of outdoor environmental fungi into homes, while bacteria are largely derived from the inhabitants.}, }
@article {pmid36416582, year = {2023}, author = {Samami, E and Aleebrahim-Dehkordi, E and Mohebalizadeh, M and Yaribash, S and Saghazadeh, A and Rezaei, N}, title = {Inosine, gut microbiota, and cancer immunometabolism.}, journal = {American journal of physiology. Endocrinology and metabolism}, volume = {324}, number = {1}, pages = {E1-E8}, doi = {10.1152/ajpendo.00207.2022}, pmid = {36416582}, issn = {1522-1555}, mesh = {Animals ; Humans ; *Gastrointestinal Microbiome ; *Neoplasms/therapy ; T-Lymphocytes ; Inosine/metabolism/pharmacology ; Carcinogenesis ; Mammals/metabolism ; Tumor Microenvironment ; }, abstract = {This article briefly reviews cancer immunity and the role of gut microbiota in carcinogenesis, followed by an understanding of mechanisms by which inosine is involved in cancer immunometabolism. The immune system plays a paradoxical role in cancer treatment. Antitumor immunity depends on the T-cell priming against tumor antigens, whereas inflammatory mediators trigger the protumor signaling in the tumor microenvironment. Studies link the microbiome with metabolism and immunity-two main factors implicated in carcinogenesis. Gut microbiota has been shown to affect both antitumor immunity and protumor immune signaling. There is mounting evidence that the human microbiome can play a role in the immunotherapeutic effects, both response and resistance. Inosine-5'-monophosphate dehydrogenase (IMPDH) is a highly conservative enzyme widely expressed in mammals. Cell signaling pathways use molecular inosine, a crucial secondary metabolite in purine metabolism and a molecular messenger. Recent research has identified inosine as a critical regulator of immune checkpoint inhibition (ICI) therapeutic response in various tumor types. Some bacterial species were found to produce inosine or its metabolite hypoxanthine and induce T-helper 1 differentiation and effector functions via the inosine-A2AR-cAMP-PKA pathway upon ICI therapy. Also, inosine acts as a substitute carbon source for T-cell metabolism in glucose-restricted environments, i.e., the tumor microenvironment, assisting T-cell proliferation and differentiation while enhancing sensitivity to ICI, reinforcing the notion that inosine metabolism might contribute to antitumor immunity. Also, inosine is a potent agonist of the adenosine receptor, A2AR, and A2AR signaling can affect T-cell responses and antitumor immunity, making the inosine-A2AR pathway blockage a candidate for cancer treatment. Further research is required to investigate inosine as a cancer immunometabolism therapy.}, }
@article {pmid36416540, year = {2022}, author = {Haffner, JJ and Katemauswa, M and Kagone, TS and Hossain, E and Jacobson, D and Flores, K and Parab, AR and Obregon-Tito, AJ and Tito, RY and Reyes, LM and Troncoso-Corzo, L and Guija-Poma, E and Meda, N and Carabin, H and Honap, TP and Sankaranarayanan, K and Lewis, CM and McCall, LI}, title = {Untargeted Fecal Metabolomic Analyses across an Industrialization Gradient Reveal Shared Metabolites and Impact of Industrialization on Fecal Microbiome-Metabolome Interactions.}, journal = {mSystems}, volume = {7}, number = {6}, pages = {e0071022}, pmid = {36416540}, issn = {2379-5077}, support = {R01 GM089886/GM/NIGMS NIH HHS/United States ; R25 AI147376/AI/NIAID NIH HHS/United States ; }, mesh = {Humans ; *Industrial Development ; RNA, Ribosomal, 16S/genetics ; Metabolomics/methods ; Metabolome ; *Microbiota/genetics ; }, abstract = {The metabolome is a central determinant of human phenotypes and includes the plethora of small molecules produced by host and microbiome or taken up from exogenous sources. However, studies of the metabolome have so far focused predominantly on urban, industrialized populations. Through an untargeted metabolomic analysis of 90 fecal samples from human individuals from Africa and the Americas-the birthplace and the last continental expansion of our species, respectively-we characterized a shared human fecal metabolome. The majority of detected metabolite features were ubiquitous across populations, despite any geographic, dietary, or behavioral differences. Such shared metabolite features included hyocholic acid and cholesterol. However, any characterization of the shared human fecal metabolome is insufficient without exploring the influence of industrialization. Here, we show chemical differences along an industrialization gradient, where the degree of industrialization correlates with metabolomic changes. We identified differential metabolite features such as amino acid-conjugated bile acids and urobilin as major metabolic correlates of these behavioral shifts. Additionally, coanalyses with over 5,000 publicly available human fecal samples and cooccurrence probability analyses with the gut microbiome highlight connections between the human fecal metabolome and gut microbiome. Our results indicate that industrialization significantly influences the human fecal metabolome, but diverse human lifestyles and behavior still maintain a shared human fecal metabolome. This study represents the first characterization of the shared human fecal metabolome through untargeted analyses of populations along an industrialization gradient. IMPORTANCE As the world becomes increasingly industrialized, understanding the biological consequences of these lifestyle shifts and what it means for past, present, and future human health is critical. Indeed, industrialization is associated with rises in allergic and autoimmune health conditions and reduced microbial diversity. Exploring these health effects on a chemical level requires consideration of human lifestyle diversity, but understanding the significance of any differences also requires knowledge of what molecular components are shared between human groups. Our study reveals the key chemistry of the human gut as defined by varied industrialization-based differences and ubiquitous shared features. Ultimately, these novel findings extend our knowledge of human molecular biology, especially as it is influenced by lifestyle and behavior, and provide steps toward understanding how human biology has changed over our species' history.}, }
@article {pmid36414613, year = {2022}, author = {Quagliariello, A and Modi, A and Innocenti, G and Zaro, V and Conati Barbaro, C and Ronchitelli, A and Boschin, F and Cavazzuti, C and Dellù, E and Radina, F and Sperduti, A and Bondioli, L and Ricci, S and Lognoli, M and Belcastro, MG and Mariotti, V and Caramelli, D and Mariotti Lippi, M and Cristiani, E and Martino, ME and Muntoni, IM and Lari, M}, title = {Ancient oral microbiomes support gradual Neolithic dietary shifts towards agriculture.}, journal = {Nature communications}, volume = {13}, number = {1}, pages = {6927}, pmid = {36414613}, issn = {2041-1723}, mesh = {Humans ; *Agriculture ; *Microbiota ; Diet ; Farmers ; Italy ; }, abstract = {The human microbiome has recently become a valuable source of information about host life and health. To date little is known about how it may have evolved during key phases along our history, such as the Neolithic transition towards agriculture. Here, we shed light on the evolution experienced by the oral microbiome during this transition, comparing Palaeolithic hunter-gatherers with Neolithic and Copper Age farmers that populated a same restricted area in Italy. We integrate the analysis of 76 dental calculus oral microbiomes with the dietary information derived from the identification of embedded plant remains. We detect a stronger deviation from the hunter-gatherer microbiome composition in the last part of the Neolithic, while to a lesser extent in the early phases of the transition. Our findings demonstrate that the introduction of agriculture affected host microbiome, supporting the hypothesis of a gradual transition within the investigated populations.}, }
@article {pmid36413391, year = {2023}, author = {Carson, MD and Warner, AJ and Hathaway-Schrader, JD and Geiser, VL and Kim, J and Gerasco, JE and Hill, WD and Lemasters, JJ and Alekseyenko, AV and Wu, Y and Yao, H and Aguirre, JI and Westwater, C and Novince, CM}, title = {Minocycline-induced disruption of the intestinal FXR/FGF15 axis impairs osteogenesis in mice.}, journal = {JCI insight}, volume = {8}, number = {1}, pages = {}, pmid = {36413391}, issn = {2379-3708}, support = {P30 DK123704/DK/NIDDK NIH HHS/United States ; I01 CX000930/CX/CSRD VA/United States ; R01 AG067510/AG/NIA NIH HHS/United States ; K08 DE025337/DE/NIDCR NIH HHS/United States ; P20 GM130457/GM/NIGMS NIH HHS/United States ; R01 DE029637/DE/NIDCR NIH HHS/United States ; P01 AG036675/AG/NIA NIH HHS/United States ; R01 DE021134/DE/NIDCR NIH HHS/United States ; T32 DE017551/DE/NIDCR NIH HHS/United States ; P20 GM121342/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Mice ; Anti-Bacterial Agents/adverse effects ; Bile Acids and Salts/metabolism ; Liver/metabolism ; Mice, Inbred C57BL ; *Minocycline/pharmacology ; *Osteogenesis ; }, abstract = {Antibiotic-induced shifts in the indigenous gut microbiota influence normal skeletal maturation. Current theory implies that gut microbiota actions on bone occur through a direct gut/bone signaling axis. However, our prior work supports that a gut/liver signaling axis contributes to gut microbiota effects on bone. Our purpose was to investigate the effects of minocycline, a systemic antibiotic treatment for adolescent acne, on pubertal/postpubertal skeletal maturation. Sex-matched specific pathogen-free (SPF) and germ-free (GF) C57BL/6T mice were administered a clinically relevant minocycline dose from age 6-12 weeks. Minocycline caused dysbiotic shifts in the gut bacteriome and impaired skeletal maturation in SPF mice but did not alter the skeletal phenotype in GF mice. Minocycline administration in SPF mice disrupted the intestinal farnesoid X receptor/fibroblast growth factor 15 axis, a gut/liver endocrine axis supporting systemic bile acid homeostasis. Minocycline-treated SPF mice had increased serum conjugated bile acids that were farnesoid X receptor (FXR) antagonists, suppressed osteoblast function, decreased bone mass, and impaired bone microarchitecture and fracture resistance. Stimulating osteoblasts with the serum bile acid profile from minocycline-treated SPF mice recapitulated the suppressed osteogenic phenotype found in vivo, which was mediated through attenuated FXR signaling. This work introduces bile acids as a potentially novel mediator of gut/liver signaling actions contributing to gut microbiota effects on bone.}, }
@article {pmid36404489, year = {2022}, author = {Loganathan, T and Priya Doss C, G}, title = {The influence of machine learning technologies in gut microbiome research and cancer studies - A review.}, journal = {Life sciences}, volume = {311}, number = {Pt A}, pages = {121118}, doi = {10.1016/j.lfs.2022.121118}, pmid = {36404489}, issn = {1879-0631}, mesh = {Humans ; *Gastrointestinal Microbiome ; Machine Learning ; *Microbiota ; *Neoplasms ; }, abstract = {Gut microbial profiles induce cancer growth and impact treatment effectiveness, tolerance, and safety. There is still more to discover about the relationship between diseases and the microbiota and its clinical consequences. Even though much of the study is still in its early phases, the 'omics' technologies were widely used for microbiome analysis due to the increased size of datasets available in public databases. However, recognizing the potential of these new technologies is difficult at times, limiting our ability to analyze a vast amount of available data critically. In this context, two subsets of AI methods, Machine Learning (ML) and Deep Learning (DL), can aid clinicians in analyzing and comprehending these large datasets. Here, we reviewed the most up-to-date ML methodologies, databases, and tools used in human microbiome research. The proposed review forecast the use of ML in microbiome research involving associations and clinical applications for diagnostics, prognostics, and therapies.}, }
@article {pmid36399893, year = {2023}, author = {Sharma, S and Hegde, P and Panda, S and Orimoloye, MO and Aldrich, CC}, title = {Drugging the microbiome: targeting small microbiome molecules.}, journal = {Current opinion in microbiology}, volume = {71}, number = {}, pages = {102234}, doi = {10.1016/j.mib.2022.102234}, pmid = {36399893}, issn = {1879-0364}, mesh = {Humans ; Pharmaceutical Preparations ; *Microbiota/physiology ; }, abstract = {The human microbiome represents a large and diverse collection of microbes that plays an integral role in human physiology and pathophysiology through interactions with the host and within the microbial community. While early work exploring links between microbiome signatures and diseases states has been associative, emerging evidence demonstrates the metabolic products of the human microbiome have more proximal causal effects on disease phenotypes. The therapeutic implications of this shift are profound as manipulation of the microbiome by the administration of live biotherapeutics, ongoing, can now be pursued alongside research efforts toward describing inhibitors of key microbiome enzymes involved in the biosynthesis of metabolites implicated in various disease states and processing of host-derived metabolites. With growing interest in 'drugging the microbiome', we review few notable microbial metabolites for which traditional drug-development campaigns have yielded compounds with therapeutic promise.}, }
@article {pmid36394327, year = {2022}, author = {Mann, E and Shekarriz, S and Surette, MG}, title = {Human Gut Metagenomes Encode Diverse GH156 Sialidases.}, journal = {Applied and environmental microbiology}, volume = {88}, number = {23}, pages = {e0175522}, pmid = {36394327}, issn = {1098-5336}, mesh = {Humans ; Glycoside Hydrolases/genetics ; *Metagenome ; *Neuraminidase/genetics/metabolism ; Polysaccharides ; Sialic Acids/metabolism ; Gastrointestinal Microbiome ; }, abstract = {The intestinal lining is protected by a mucous barrier composed predominantly of complex carbohydrates. Gut microbes employ diverse glycoside hydrolases (GHs) to liberate mucosal sugars as a nutrient source to facilitate host colonization. Intensive catabolism of mucosal glycans, however, may contribute to barrier erosion, pathogen encroachment, and inflammation. Sialic acid is an acidic sugar featured at terminal positions of host glycans. Characterized sialidases from the microbiome belong to the GH33 family, according to CAZy (Carbohydrate-Active enZYmes Database). In 2018 a functional metagenomics screen using thermal spring DNA uncovered the founding member of the GH156 sialidase family, the presence of which has yet to be reported in the context of the human microbiome. A subset of GH156 sequences from the CAZy database containing key sialidase residues was used to build a hidden Markov model. HMMsearch against public databases revealed ~10× more putative GH156 sialidases than currently cataloged by CAZy. Represented phyla include Bacteroidota, Verrucomicrobiota, and Firmicutes_A from human microbiomes, all of which play notable roles in carbohydrate fermentation. Analyses of metagenomic data sets revealed that GH156s are frequently encoded in metagenomes, with a greater variety and abundance of GH156 genes observed in traditional hunter-gatherer or agriculturalist societies than in industrialized societies, particularly relative to individuals with inflammatory bowel disease (IBD). Nineteen GH156s were recombinantly expressed and assayed for sialidase activity. The five GH156 sialidases identified here share limited sequence identity to each other or the founding GH156 family member and are representative of a large subset of the family. IMPORTANCE Sialic acids occupy terminal positions of human glycans where they act as receptors for microbes, toxins, and immune signaling molecules. Microbial enzymes that remove sialic acids, sialidases, are abundant in the human microbiome where they may contribute to shaping the microbiota community structure or contribute to pathology. Furthermore, sialidases have proven to hold therapeutic potential for cancer therapy. Here, we examined the sequence space of a sialidase family of enzymes, GH156, previously unknown in the human gut environment. Our analyses suggest that human populations with disparate dietary practices harbor distinct varieties and abundances of GH156-encoding genes. Furthermore, we demonstrate the sialidase activity of 5 gut-derived GH156s. These results expand the diversity of sialidases that may contribute to host glycan degradation, and these sequences may have biotechnological or clinical utility.}, }
@article {pmid36394178, year = {2022}, author = {Bjarnsholt, T and Ralfkiaer, U and Malone, M}, title = {APMIS 2022 focus issue on human microbiome in disease and pathology.}, journal = {APMIS : acta pathologica, microbiologica, et immunologica Scandinavica}, volume = {130}, number = {12}, pages = {689}, doi = {10.1111/apm.13283}, pmid = {36394178}, issn = {1600-0463}, mesh = {Humans ; *Microbiota ; Disease ; Periodicals as Topic ; }, }
@article {pmid36385397, year = {2023}, author = {Schoch, JJ and Gauthier, J and Gharaibeh, RZ and Jobin, C and Bohannon, M and Neu, J and Parker, L}, title = {Skin microbiome sampling in the preterm neonate.}, journal = {Pediatric dermatology}, volume = {40}, number = {1}, pages = {129-131}, pmid = {36385397}, issn = {1525-1470}, support = {KL2 TR001429/TR/NCATS NIH HHS/United States ; 1KL2TROO1429/TR/NCATS NIH HHS/United States ; //Society for Pediatric Dermatology/ ; //Pediatric Dermatology Research Alliance/ ; }, mesh = {Infant, Newborn ; Humans ; *Infant, Premature ; Skin ; *Microbiota ; }, abstract = {Despite advances in our understanding of the human microbiome, there exist significant knowledge gaps in our understanding of the skin microbiome of the preterm neonate. Herein, we describe skin microbiome sampling of six preterm neonates at multiple timepoints, and compare the skin microbiome samples to environmental (crib/isolette swabs) and negative controls. Samples of the same type (skin, crib, control) were more similar than when compared by week or by patient.}, }
@article {pmid36384106, year = {2022}, author = {Bootz-Maoz, H and Pearl, A and Melzer, E and Malnick, S and Sharon, E and Bennet, Y and Tsentsarevsky, R and Abuchatzera, S and Amidror, S and Aretz, E and Azriel, S and Gam Ze Letova, C and Naama, M and Shoval, I and Yaron, O and Karako-Lampert, S and Bel, S and Yissachar, N}, title = {Diet-induced modifications to human microbiome reshape colonic homeostasis in irritable bowel syndrome.}, journal = {Cell reports}, volume = {41}, number = {7}, pages = {111657}, doi = {10.1016/j.celrep.2022.111657}, pmid = {36384106}, issn = {2211-1247}, mesh = {Humans ; *Irritable Bowel Syndrome/therapy ; Diet, Carbohydrate-Restricted ; *Gastrointestinal Microbiome ; Homeostasis ; }, abstract = {Changes in microbiome composition are associated with a wide array of human diseases, turning the human microbiota into an attractive target for therapeutic intervention. Yet, clinical translation of these findings requires the establishment of causative connections between specific microbial taxa and their functional impact on host tissues. Here, we infuse gut organ cultures with longitudinal microbiota samples collected from therapy-naive patients with irritable bowel syndrome (IBS) under a low-fermentable oligo-, di-, mono-saccharides and polyols (FODMAP) diet. We show that post-diet microbiota regulates intestinal expression of inflammatory and neuro-muscular gene sets. Specifically, we identify Bifidobacterium adolescentis as a diet-sensitive pathobiont that alters tight junction integrity and disrupts gut barrier functions. Collectively, we present a pathway discovery platform for mechanistic dissection and identification of functional diet-host-microbiota modules. Our data support the hypothesis that the gut microbiota mediates the beneficial effects of a low-FODMAP diet and reinforce the potential feasibility of microbiome-based therapies in IBS.}, }
@article {pmid36380339, year = {2022}, author = {Haque, MM and Yerex, K and Kelekis-Cholakis, A and Duan, K}, title = {Advances in novel therapeutic approaches for periodontal diseases.}, journal = {BMC oral health}, volume = {22}, number = {1}, pages = {492}, pmid = {36380339}, issn = {1472-6831}, mesh = {Humans ; *Quorum Sensing ; Biofilms ; *Periodontal Diseases/therapy ; Bacteria ; Anti-Bacterial Agents/therapeutic use/pharmacology ; }, abstract = {Periodontal diseases are pathological processes resulting from infections and inflammation affecting the periodontium or the tissue surrounding and supporting the teeth. Pathogenic bacteria living in complex biofilms initiate and perpetuate this disease in susceptible hosts. In some cases, broad-spectrum antibiotic therapy has been a treatment of choice to control bacterial infection. However, increasing antibiotic resistance among periodontal pathogens has become a significant challenge when treating periodontal diseases. Thanks to the improved understanding of the pathogenesis of periodontal disease, which involves the host immune response, and the importance of the human microbiome, the primary goal of periodontal therapy has shifted, in recent years, to the restoration of homeostasis in oral microbiota and its harmonious balance with the host periodontal tissues. This shift in therapeutic goals and the drug resistance challenge call for alternative approaches to antibiotic therapy that indiscriminately eliminate harmful or beneficial bacteria. In this review, we summarize the recent advancement of alternative methods and new compounds that offer promising potential for the treatment and prevention of periodontal disease. Agents that target biofilm formation, bacterial quorum-sensing systems and other virulence factors have been reviewed. New and exciting microbiome approaches, such as oral microbiota replacement therapy and probiotic therapy for periodontal disease, are also discussed.}, }
@article {pmid36378489, year = {2022}, author = {Gupta, VK and Bakshi, U and Chang, D and Lee, AR and Davis, JM and Chandrasekaran, S and Jin, YS and Freeman, MF and Sung, J}, title = {TaxiBGC: a Taxonomy-Guided Approach for Profiling Experimentally Characterized Microbial Biosynthetic Gene Clusters and Secondary Metabolite Production Potential in Metagenomes.}, journal = {mSystems}, volume = {7}, number = {6}, pages = {e0092522}, pmid = {36378489}, issn = {2379-5077}, support = {R35 GM133475/GM/NIGMS NIH HHS/United States ; }, mesh = {Humans ; Metagenome/genetics ; *Microbiota/genetics ; *Gastrointestinal Microbiome/genetics ; Computational Biology ; Multigene Family/genetics ; }, abstract = {Biosynthetic gene clusters (BGCs) in microbial genomes encode bioactive secondary metabolites (SMs), which can play important roles in microbe-microbe and host-microbe interactions. Given the biological significance of SMs and the current profound interest in the metabolic functions of microbiomes, the unbiased identification of BGCs from high-throughput metagenomic data could offer novel insights into the complex chemical ecology of microbial communities. Currently available tools for predicting BGCs from shotgun metagenomes have several limitations, including the need for computationally demanding read assembly, predicting a narrow breadth of BGC classes, and not providing the SM product. To overcome these limitations, we developed taxonomy-guided identification of biosynthetic gene clusters (TaxiBGC), a command-line tool for predicting experimentally characterized BGCs (and inferring their known SMs) in metagenomes by first pinpointing the microbial species likely to harbor them. We benchmarked TaxiBGC on various simulated metagenomes, showing that our taxonomy-guided approach could predict BGCs with much-improved performance (mean F1 score, 0.56; mean PPV score, 0.80) compared with directly identifying BGCs by mapping sequencing reads onto the BGC genes (mean F1 score, 0.49; mean PPV score, 0.41). Next, by applying TaxiBGC on 2,650 metagenomes from the Human Microbiome Project and various case-control gut microbiome studies, we were able to associate BGCs (and their SMs) with different human body sites and with multiple diseases, including Crohn's disease and liver cirrhosis. In all, TaxiBGC provides an in silico platform to predict experimentally characterized BGCs and their SM production potential in metagenomic data while demonstrating important advantages over existing techniques. IMPORTANCE Currently available bioinformatics tools to identify BGCs from metagenomic sequencing data are limited in their predictive capability or ease of use to even computationally oriented researchers. We present an automated computational pipeline called TaxiBGC, which predicts experimentally characterized BGCs (and infers their known SMs) in shotgun metagenomes by first considering the microbial species source. Through rigorous benchmarking techniques on simulated metagenomes, we show that TaxiBGC provides a significant advantage over existing methods. When demonstrating TaxiBGC on thousands of human microbiome samples, we associate BGCs encoding bacteriocins with different human body sites and diseases, thereby elucidating a possible novel role of this antibiotic class in maintaining the stability of microbial ecosystems throughout the human body. Furthermore, we report for the first time gut microbial BGC associations shared among multiple pathologies. Ultimately, we expect our tool to facilitate future investigations into the chemical ecology of microbial communities across diverse niches and pathologies.}, }
@article {pmid36364808, year = {2022}, author = {Drake, AM and Coughlan, MT and Christophersen, CT and Snelson, M}, title = {Resistant Starch as a Dietary Intervention to Limit the Progression of Diabetic Kidney Disease.}, journal = {Nutrients}, volume = {14}, number = {21}, pages = {}, pmid = {36364808}, issn = {2072-6643}, mesh = {Animals ; Humans ; Resistant Starch ; Starch/therapeutic use/metabolism ; *Diabetic Nephropathies/prevention &amp; control ; Dietary Fiber/therapeutic use/metabolism ; Fatty Acids, Volatile/metabolism ; *Diabetes Mellitus ; }, abstract = {Diabetes is the leading cause of kidney disease, and as the number of individuals with diabetes increases there is a concomitant increase in the prevalence of diabetic kidney disease (DKD). Diabetes contributes to the development of DKD through a number of pathways, including inflammation, oxidative stress, and the gut-kidney axis, which may be amenable to dietary therapy. Resistant starch (RS) is a dietary fibre that alters the gut microbial consortium, leading to an increase in the microbial production of short chain fatty acids. Evidence from animal and human studies indicate that short chain fatty acids are able to attenuate inflammatory and oxidative stress pathways, which may mitigate the progression of DKD. In this review, we evaluate and summarise the evidence from both preclinical models of DKD and clinical trials that have utilised RS as a dietary therapy to limit the progression of DKD.}, }
@article {pmid36362106, year = {2022}, author = {Piccioni, A and Rosa, F and Manca, F and Pignataro, G and Zanza, C and Savioli, G and Covino, M and Ojetti, V and Gasbarrini, A and Franceschi, F and Candelli, M}, title = {Gut Microbiota and Clostridium difficile: What We Know and the New Frontiers.}, journal = {International journal of molecular sciences}, volume = {23}, number = {21}, pages = {}, pmid = {36362106}, issn = {1422-0067}, mesh = {Humans ; *Clostridioides difficile ; *Gastrointestinal Microbiome/physiology ; *Enterocolitis, Pseudomembranous/microbiology ; *Clostridium Infections/microbiology ; *Microbiota ; }, abstract = {Our digestive system, particularly our intestines, harbors a vast amount of microorganisms, whose genetic makeup is referred to as the microbiome. Clostridium difficile is a spore-forming Gram-positive bacterium, which can cause an infection whose symptoms range from asymptomatic colonization to fearsome complications such as the onset of toxic megacolon. The relationship between gut microbiota and Clostridium difficile infection has been studied from different perspectives. One of the proposed strategies is to be able to specifically identify which types of microbiota alterations are most at risk for the onset of CDI. In this article, we understood once again how crucial the role of the human microbiota is in health and especially how crucial it becomes, in the case of its alteration, for the individual's disease. Clostridium difficile infection is an emblematic example of how a normal and physiological composition of the human microbiome can play a very important role in immune defense against such a fearsome disease.}, }
@article {pmid36362056, year = {2022}, author = {Ustianowska, K and Ustianowski, &#x141; and Machaj, F and Gorący, A and Rosik, J and Szostak, B and Szostak, J and Pawlik, A}, title = {The Role of the Human Microbiome in the Pathogenesis of Pain.}, journal = {International journal of molecular sciences}, volume = {23}, number = {21}, pages = {}, pmid = {36362056}, issn = {1422-0067}, mesh = {Female ; Humans ; *Visceral Pain/pathology ; Brain/pathology ; Dysbiosis/pathology ; *Microbiota ; *Gastrointestinal Microbiome/physiology ; *Probiotics ; *Chronic Pain ; }, abstract = {Understanding of the gut microbiome's role in human physiology developed rapidly in recent years. Moreover, any alteration of this microenvironment could lead to a pathophysiological reaction of numerous organs. It results from the bidirectional communication of the gastrointestinal tract with the central nervous system, called the gut-brain axis. The signals in the gut-brain axis are mediated by immunological, hormonal, and neural pathways. However, it is also influenced by microorganisms in the gut. The disturbances in the gut-brain axis are associated with gastrointestinal syndromes, but recently their role in the development of different types of pain was reported. The gut microbiome could be the factor in the central sensitization of chronic pain by regulating microglia, astrocytes, and immune cells. Dysbiosis could lead to incorrect immune responses, resulting in the development of inflammatory pain such as endometriosis. Furthermore, chronic visceral pain, associated with functional gastrointestinal disorders, could result from a disruption in the gut microenvironment. Any alteration in the gut-brain axis could also trigger migraine attacks by affecting cytokine expression. Understanding the gut microbiome's role in pain pathophysiology leads to the development of analgetic therapies targeting microorganisms. Probiotics, FODMAP diet, and fecal microbiota transplantation are reported to be beneficial in treating visceral pain.}, }
@article {pmid36357382, year = {2022}, author = {Liu, Y and Elworth, RAL and Jochum, MD and Aagaard, KM and Treangen, TJ}, title = {De novo identification of microbial contaminants in low microbial biomass microbiomes with Squeegee.}, journal = {Nature communications}, volume = {13}, number = {1}, pages = {6799}, pmid = {36357382}, issn = {2041-1723}, support = {P01 AI152999/AI/NIAID NIH HHS/United States ; R01 DK128187/DK/NIDDK NIH HHS/United States ; R01 HD091731/HD/NICHD NIH HHS/United States ; T15 LM007093/LM/NLM NIH HHS/United States ; T32 HL098069/HL/NHLBI NIH HHS/United States ; R01 NR014792/NR/NINR NIH HHS/United States ; T32 HD098068/HD/NICHD NIH HHS/United States ; }, mesh = {Humans ; Biomass ; *Microbiota/genetics ; Metagenomics/methods ; Metagenome ; Specimen Handling ; }, abstract = {Computational analysis of host-associated microbiomes has opened the door to numerous discoveries relevant to human health and disease. However, contaminant sequences in metagenomic samples can potentially impact the interpretation of findings reported in microbiome studies, especially in low-biomass environments. Contamination from DNA extraction kits or sampling lab environments leaves taxonomic "bread crumbs" across multiple distinct sample types. Here we describe Squeegee, a de novo contamination detection tool that is based upon this principle, allowing the detection of microbial contaminants when negative controls are unavailable. On the low-biomass samples, we compare Squeegee predictions to experimental negative control data and show that Squeegee accurately recovers putative contaminants. We analyze samples of varying biomass from the Human Microbiome Project and identify likely, previously unreported kit contamination. Collectively, our results highlight that Squeegee can identify microbial contaminants with high precision and thus represents a computational approach for contaminant detection when negative controls are unavailable.}, }
@article {pmid36351016, year = {2022}, author = {Chen, J and Zhang, P and Zhao, Y and Zhao, J and Wu, X and Zhang, R and Cha, R and Yao, Q and Gao, Y}, title = {Nitroreductase-instructed supramolecular assemblies for microbiome regulation to enhance colorectal cancer treatments.}, journal = {Science advances}, volume = {8}, number = {45}, pages = {eadd2789}, pmid = {36351016}, issn = {2375-2548}, mesh = {Humans ; Mice ; Animals ; *Colorectal Neoplasms/drug therapy/pathology ; Fusobacterium nucleatum/physiology ; *Gastrointestinal Microbiome ; Nitroreductases ; }, abstract = {The development of human microbiome has collectively correlated the sophisticated interactions between Fusobacterium nucleatum and colorectal cancers (CRCs). However, the treatment of CRC via disruption of gastrointestinal flora remains less explored. Aiming at the up-regulated activity of nitroreductase in F. nucleatum-infected tumors, here, we developed the nitroreductase-instructed supramolecular self-assembly. The designed assembly precursors underwent enzymatic transformation to form assemblies, which agglutinated F. nucleatum and eradicated the targeted bacteria. These assemblies with anti-F. nucleatum activity could further alleviate the bacteria-induced drug resistance effect, thus sensitizing CRC cells against chemo-drugs. Eventually, in mice bearing F. nucleatum-infected CRC, the local introduction of nitroreductase-instructed assemblies could efficiently inhibit the tumor growth. Overall, this study incorporated nitroreductase to broaden the toolbox of enzyme-instructed supramolecular self-assembly. The local introduction of nitroreductase-instructed assemblies could target F. nucleatum to eliminate its contribution to CRC drug resistance and ameliorate chemotherapy outcomes.}, }
@article {pmid36348188, year = {2022}, author = {Rasmussen, N}, title = {René Dubos, the Autochthonous Flora, and the Discovery of the Microbiome.}, journal = {Journal of the history of biology}, volume = {55}, number = {3}, pages = {537-558}, pmid = {36348188}, issn = {1573-0387}, mesh = {Animals ; Humans ; *Microbiota ; *Anthozoa ; Symbiosis ; }, abstract = {Now characterised by high-throughput sequencing methods that enable the study of microbes without lab culture, the human "microbiome" (the microbial flora of the body) is said to have revolutionary implications for biology and medicine. According to many experts, we must now understand ourselves as "holobionts" like lichen or coral, multispecies superorganisms that consist of animal and symbiotic microbes in combination, because normal physiological function depends on them. Here I explore the 1960s research of biologist René Dubos, a forerunner figure mentioned in some historical accounts of the microbiome, and argue that he arrived at the superorganism concept 40 years before the Human Microbiome Project. This raises the question of why his contribution was not hailed as revolutionary at the time and why Dubos is not remembered for it.}, }
@article {pmid36342297, year = {2022}, author = {Mirabelli, C and Santos-Ferreira, N and Gillilland, MG and Cieza, RJ and Colacino, JA and Sexton, JZ and Neyts, J and Taube, S and Rocha-Pereira, J and Wobus, CE}, title = {Human Norovirus Efficiently Replicates in Differentiated 3D-Human Intestinal Enteroids.}, journal = {Journal of virology}, volume = {96}, number = {22}, pages = {e0085522}, pmid = {36342297}, issn = {1098-5514}, support = {UL1TR002240//UM | Michigan Institute for Clinical and Health Research (MICHR)/ ; P30 ES017885/ES/NIEHS NIH HHS/United States ; P30ES017885//HHS | NIH | OSC | Common Fund (NIH Common Fund)/ ; R01 ES028802/ES/NIEHS NIH HHS/United States ; P30DK034933//HHS | NIH | OSC | Common Fund (NIH Common Fund)/ ; }, mesh = {Humans ; *Norovirus/physiology ; Pyrazoles ; *Caliciviridae Infections ; *Gastroenteritis ; Antiviral Agents/pharmacology ; }, abstract = {Human norovirus (HNoV) accounts for one-fifth of all acute viral gastroenteritis worldwide and an economic burden of ~$60 billion globally. The lack of treatment options against HNoV is in part due to the lack of cultivation systems. Recently, a model of infection in biopsy-derived human intestinal enteroids (HIE) has been described: 3D-HIE are first dispersed in 2D-monolayers and differentiated prior to infection, resulting in a labor-intensive, time-consuming procedure. Here, we present an alternative protocol for HNoV infection of 3D-HIE. We found that 3D-HIE differentiated as efficiently as 2D-monolayers. In addition, immunofluorescence-based quantification of UEA-1, a lectin that stains the villus brush border, revealed that ~80% of differentiated 3D-HIE spontaneously undergo polarity inversion, allowing for viral infection without the need for microinjection. Infection with HNoV GII.4-positive stool samples attained a fold-increase over inoculum of ~2 Log10 at 2 days postinfection or up to 3.5 Log10 when ruxolitinib, a JAK1/2-inhibitor, was added. Treatment of GII.4-infected 3D-HIE with the polymerase inhibitor 2'-C-Methylcytidine (2CMC) and other antivirals showed a reduction in viral infection, suggesting that 3D-HIE are an excellent platform to test anti-infectives. The transcriptional host response to HNoV was then investigated by RNA sequencing in infected versus uninfected 3D-HIE in the presence of ruxolitinib to focus on virus-associated signatures while limiting interferon-stimulated gene signatures. The analysis revealed upregulated hormone and neurotransmitter signal transduction pathways and downregulated glycolysis and hypoxia-response pathways upon HNoV infection. Overall, 3D-HIE have proven to be a highly robust model to study HNoV infection, screen antivirals, and to investigate the host response to HNoV infection. IMPORTANCE The human norovirus (HNoV) clinical and socio-economic impact calls for immediate action in the development of anti-infectives. Physiologically relevant in vitro models are hence needed to study HNoV biology, tropism, and mechanisms of viral-associated disease, and also as a platform to identify antiviral agents. Biopsy-derived human intestinal enteroids are a biomimetic of the intestinal epithelium and were recently described as a model that supports HNoV infection. However, the established protocol is time-consuming and labor-intensive. Therefore, we sought to develop a simplified and robust alternative model of infection in 3D enteroids that undergoes differentiation and spontaneous polarity inversion. Advantages of this model are the shorter experimental time, better infection yield, and spatial integrity of the intestinal epithelium. This model is potentially suitable for the study of other pathogens that infect intestinal cells from the apical surface but also for unraveling the interactions between intestinal epithelium and indigenous bacteria of the human microbiome.}, }
@article {pmid36337619, year = {2022}, author = {Akimbekov, NS and Digel, I and Yerezhepov, AY and Shardarbek, RS and Wu, X and Zha, J}, title = {Nutritional factors influencing microbiota-mediated colonization resistance of the oral cavity: A literature review.}, journal = {Frontiers in nutrition}, volume = {9}, number = {}, pages = {1029324}, pmid = {36337619}, issn = {2296-861X}, abstract = {The oral cavity is a key biocenosis for many distinct microbial communities that interact with both the external environment and internal body systems. The oral microbiota is a vital part of the human microbiome. It has been developed through mutual interactions among the environment, host physiological state, and microbial community composition. Indigenious microbiota of the oral cavity is one of the factors that prevent adhesion and invasion of pathogens on the mucous membrane, i.e., the development of the infectious process and thereby participating in the implementation of one of the mechanisms of local immunity-colonization resistance. The balance between bacterial symbiosis, microbial virulence, and host resistance ensures the integrity of the oral cavity. In this review we have tried to address how nutritional factors influence integrity of the oral indigenous microbiota and its involvement in colonization resistance.}, }
@article {pmid36335804, year = {2023}, author = {Cuozzo, S and de Moreno de LeBlanc, A and LeBlanc, JG and Hoffmann, N and Tortella, GR}, title = {Streptomyces genus as a source of probiotics and its potential for its use in health.}, journal = {Microbiological research}, volume = {266}, number = {}, pages = {127248}, doi = {10.1016/j.micres.2022.127248}, pmid = {36335804}, issn = {1618-0623}, mesh = {Animals ; *Streptomyces ; *Probiotics ; *Gastrointestinal Microbiome ; *Microbiota ; Anti-Bacterial Agents/pharmacology ; }, abstract = {The effect of a probiotic on gut microbiota depends not only on the species of microorganism but specifically on the strain. In human beings, as in other animals, specific probiotics have been associated with numerous beneficial properties, which include weight modulation (gain or loss), immune modulation, and prevention of many disorders such as lactose intolerance, cardiovascular diseases, and antibiotic-associated diarrhoea. Streptomyces are an essential group of soil bacteria in the Actinomycetes family. They are related to producing a wide range of secondary metabolites known for their beneficial effects on human health. However, according to the human microbiome analysis, a lower prevalence of Streptomyces genus exists than in other non-human microbiomes. This difference can be associated with current lifestyles. In this article, we review the benefits associated with different compounds produced by Streptomyces, with a particular focus on the production of exopolysaccharides, antibiotics, and other secondary metabolites and the potential innovative use of Streptomyces spp. as probiotics.}, }
@article {pmid36329122, year = {2022}, author = {Clarke, T and Brinkac, L and Greco, C and Alleyne, AT and Carrasco, P and Inostroza, C and Tau, T and Wisitrasameewong, W and Torralba, MG and Nelson, K and Singh, H}, title = {Sampling from four geographically divergent young female populations demonstrates forensic geolocation potential in microbiomes.}, journal = {Scientific reports}, volume = {12}, number = {1}, pages = {18547}, pmid = {36329122}, issn = {2045-2322}, support = {2015-R2-CX-K036//National Institute of Justice/ ; }, mesh = {Humans ; Female ; RNA, Ribosomal, 16S/genetics ; *Microbiota/genetics ; DNA, Bacterial/genetics ; Feces/microbiology ; Specimen Handling ; }, abstract = {Studies of human microbiomes using new sequencing techniques have increasingly demonstrated that their ecologies are partly determined by the lifestyle and habits of individuals. As such, significant forensic information could be obtained from high throughput sequencing of the human microbiome. This approach, combined with multiple analytical techniques demonstrates that bacterial DNA can be used to uniquely identify an individual and to provide information about their life and behavioral patterns. However, the transformation of these findings into actionable forensic information, including the geolocation of the samples, remains limited by incomplete understanding of the effects of confounding factors and the paucity of diverse sequences. We obtained 16S rRNA sequences of stool and oral microbiomes collected from 206 young and healthy females from four globally diverse populations, in addition to supporting metadata, including dietary and medical information. Analysis of these microbiomes revealed detectable geolocation signals between the populations, even for populations living within the same city. Accounting for other lifestyle variables, such as diet and smoking, lessened but does not remove the geolocation signal.}, }
@article {pmid36322821, year = {2022}, author = {Saleem, A and Ikram, A and Dikareva, E and Lahtinen, E and Matharu, D and Pajari, AM and de Vos, WM and Hasan, F and Salonen, A and Jian, C}, title = {Unique Pakistani gut microbiota highlights population-specific microbiota signatures of type 2 diabetes mellitus.}, journal = {Gut microbes}, volume = {14}, number = {1}, pages = {2142009}, pmid = {36322821}, issn = {1949-0984}, mesh = {Adult ; Humans ; *Gastrointestinal Microbiome/genetics ; *Diabetes Mellitus, Type 2/microbiology ; Pakistan ; *Microbiota ; RNA, Ribosomal, 16S/genetics ; Bacteria/genetics ; *Actinobacteria/genetics ; }, abstract = {Biogeographic variations in the gut microbiota are pivotal to understanding the global pattern of host-microbiota interactions in prevalent lifestyle-related diseases. Pakistani adults, having an exceptionally high prevalence of type 2 diabetes mellitus (T2D), are one of the most understudied populations in microbiota research to date. The aim of the present study is to examine the gut microbiota across individuals from Pakistan and other populations of non-industrialized and industrialized lifestyles with a focus on T2D. The fecal samples from 94 urban-dwelling Pakistani adults with and without T2D were profiled by bacterial 16S ribosomal RNA gene and fungal internal transcribed spacer (ITS) region amplicon sequencing and eubacterial qPCR, and plasma samples quantified for circulating levels of lipopolysaccharide-binding protein (LBP) and the activation ability of Toll-like receptor (TLR)-signaling. Publicly available datasets generated with comparable molecular methods were retrieved for comparative analysis of the bacterial microbiota. Overall, urbanized Pakistanis' gut microbiota was similar to that of transitional or non-industrialized populations, depleted in Akkermansiaceae and enriched in Prevotellaceae (dominated by the non-Westernized clades of Prevotella copri). The relatively high proportion of Atopobiaceae appeared to be a unique characteristic of the Pakistani gut microbiota. The Pakistanis with T2D had elevated levels of LBP and TLR-signaling in circulation as well as gut microbial signatures atypical of other populations, e.g., increased relative abundance of Libanicoccus/Parolsenella, limiting the inter-population extrapolation of gut microbiota-based classifiers for T2D. Taken together, our findings call for a more global representation of understudied populations to extend the applicability of microbiota-based diagnostics and therapeutics.}, }
@article {pmid36321825, year = {2022}, author = {Stuivenberg, GA and Chmiel, JA and Akouris, PP and Burton, JP and Reid, G}, title = {Probiotic Bifidobacteria Mitigate the Deleterious Effects of para-Cresol in a Drosophila melanogaster Toxicity Model.}, journal = {mSphere}, volume = {7}, number = {6}, pages = {e0044622}, pmid = {36321825}, issn = {2379-5042}, mesh = {Animals ; Drosophila melanogaster ; Uremic Toxins ; *Probiotics/therapeutic use ; *Renal Insufficiency, Chronic/therapy/microbiology ; Sulfates ; Sodium Channels ; *Drosophila Proteins ; }, abstract = {Renal impairment associated with chronic kidney disease (CKD) causes the buildup of uremic toxins that are deleterious to patient health. Current therapies that manage toxin accumulation in CKD offer an incomplete therapeutic effect against toxins such as para-cresol (p-cresol) and p-cresyl sulfate. Probiotic therapies can exploit the wealth of microbial diversity to reduce toxin accumulation. Using in vitro culture techniques, strains of lactobacilli and bifidobacteria from a 24-strain synbiotic were investigated for their ability to remove p-cresol. Four strains of bifidobacteria internalized p-cresol from the extracellular environment. The oral supplementation of these toxin-clearing probiotics was more protective than control strains in a Drosophila melanogaster toxicity model. Bifidobacterial supplementation was also associated with higher abundance of lactobacilli in the gut microbiota of p-cresol-exposed flies. The present findings suggest that these strains might reduce p-cresol in the gut in addition to increasing the prevalence of other beneficial bacteria, such as lactobacilli, and should be tested clinically to normalize the dysbiotic gut microbiota observed in CKD patients. IMPORTANCE Chronic kidney disease (CKD) affects approximately 10% of the global population and has limited treatment options. The accumulation of gut microbiota-derived uremic toxins, such as para-cresol (p-cresol) and p-cresyl sulfate, is associated with the onset of comorbidities (i.e., atherosclerosis and cognitive disorders) in CKD. Unfortunately, dialysis, the gold standard therapy is unable to remove these toxins from the bloodstream due to their highly protein-bound nature. Some strains of Bifidobacterium have metabolic properties that may be useful in managing uremic toxicity. Using a Drosophila model, the present work highlights why dosing with certain probiotic strains may be clinically useful in CKD management.}, }
@article {pmid36321381, year = {2022}, author = {Das, BK}, title = {Altered gut microbiota in hepatocellular carcinoma: Insights into the pathogenic mechanism and preclinical to clinical findings.}, journal = {APMIS : acta pathologica, microbiologica, et immunologica Scandinavica}, volume = {130}, number = {12}, pages = {719-740}, doi = {10.1111/apm.13282}, pmid = {36321381}, issn = {1600-0463}, mesh = {Humans ; *Gastrointestinal Microbiome ; *Carcinoma, Hepatocellular/pathology ; *Liver Neoplasms/pathology ; Dysbiosis/complications ; *Probiotics/therapeutic use ; *Non-alcoholic Fatty Liver Disease ; }, abstract = {Hepatocellular carcinoma (HCC) is the third leading cause of cancer death worldwide. It is usually the result of pre-existing liver damage caused by hepatitis B and/or C virus infection, alcohol consumption, nonalcoholic steatohepatitis (NASH), aflatoxin exposure, liver cirrhosis, obesity, and diabetes. A growing body of evidence suggests that gut microbes have a role in cancer genesis. More research into the microbiome gut-liver axis has recently contributed to understanding how the gut microbiome facilitates liver disease or even HCC progression. This review focuses on the preclinical results of gut-related hepatocarcinogenesis and probiotics, prebiotics, and antibiotics as therapeutic interventions to maintain gut microbial flora and minimize HCC-associated symptoms. Understanding the mechanistic link between the gut microbiota, host, and cancer progression could aid us in elucidating the cancer-related pathways and drive us toward preventing HCC-associated gut microbiota dysbiosis.}, }
@article {pmid36319696, year = {2023}, author = {Tierney, BT and Versalovic, J and Fasano, A and Petrosino, JF and Chumpitazi, BP and Mayer, EA and Boetes, J and Smits, G and Parkar, SG and Voreades, N and Kartal, E and Al-Ghalith, GA and Pane, M and Bron, PA and Reid, G and Dhir, R and Mason, CE}, title = {Functional response to a microbial synbiotic in the gastrointestinal system of children: a randomized clinical trial.}, journal = {Pediatric research}, volume = {93}, number = {7}, pages = {2005-2013}, pmid = {36319696}, issn = {1530-0447}, mesh = {Child ; Humans ; Infant ; *Synbiotics ; Gastrointestinal Tract/microbiology ; *Probiotics/therapeutic use ; Constipation/therapy ; Feces/microbiology ; Double-Blind Method ; }, abstract = {BACKGROUND: Oral microbial therapy has been studied as an intervention for a range of gastrointestinal disorders. Though research suggests that microbial exposure may affect the gastrointestinal system, motility, and host immunity in a pediatric population, data have been inconsistent, with most prior studies being in neither a randomized nor placebo-controlled setting. The aim of this randomized, placebo-controlled study was to evaluate the efficacy of a synbiotic on increasing weekly bowel movements (WBMs) in constipated children.<br><br>METHODS: Sixty-four children (3-17 years of age) were randomized to receive a synbiotic (n&#x2009;=&#x2009;33) comprising mixed-chain length oligosaccharides and nine microbial strains, or placebo (n&#x2009;=&#x2009;31) for 84 days. Stool microbiota was analyzed on samples collected at baseline and completion. The primary outcome was a change from baseline of WBMs in the treatment group compared to placebo.<br><br>RESULTS: Treatment increased (p&#x2009;<&#x2009;0.05) the number of WBMs in children with low baseline WBMs, despite broadly distinctive baseline microbiome signatures. Sequencing revealed that low baseline microbial richness in the treatment group significantly anticipated improvements in constipation (p&#x2009;=&#x2009;0.00074).<br><br>CONCLUSIONS: These findings suggest the potential for (i) multi-species-synbiotic interventions to improve digestive health in a pediatric population and (ii) bioinformatics-based methods to predict response to microbial interventions in children.<br><br>IMPACT: Synbiotic microbial treatment improved the number of spontaneous weekly bowel movements in children compared to placebo. Intervention induced an increased abundance of bifidobacteria in children, compared to placebo. All administered probiotic species were enriched in the gut microbiome of the intervention group compared to placebo. Baseline microbial richness demonstrated potential as a predictive biomarker for response to intervention.}, }
@article {pmid36318354, year = {2022}, author = {Zhan, Y and Liu, Q and Zhang, B and Huang, X and Lu, Q}, title = {Recent advances in systemic lupus erythematosus and microbiota: from bench to bedside.}, journal = {Frontiers of medicine}, volume = {16}, number = {5}, pages = {686-700}, pmid = {36318354}, issn = {2095-0225}, mesh = {Humans ; Female ; *Gastrointestinal Microbiome ; *Lupus Erythematosus, Systemic/genetics/therapy ; *Microbiota ; Autoimmunity ; Immune System ; }, abstract = {Systemic lupus erythematosus (SLE) is a complicated autoimmune disease affecting multiple systems and organs. It is highly heterogeneous, and it preferentially affects women at childbearing age, causing worldwide social burden. The pathogenesis of SLE mostly involves genetic predisposition, epigenetic dysregulation, overactivation of the immune system, and environment factors. Human microbiome, which is mostly composed of microbiota colonized in the gut, skin, and oral cavity, provides a natural microbiome barrier against environmental risks. The past decade of research has demonstrated a strong association between microbiota and metabolic diseases or gastrointestinal diseases. However, the role of microbiota in autoimmunity remains largely unknown until recently, when the technological and methodological progress facilitates further microbiota research in SLE. In this review, the latest research about the role and mechanisms of microbiota in SLE and the advances in the development of diagnostic and therapeutic strategies based on microbiota for SLE were summarized.}, }
@article {pmid36317983, year = {2023}, author = {Aggarwal, N and Kitano, S and Puah, GRY and Kittelmann, S and Hwang, IY and Chang, MW}, title = {Microbiome and Human Health: Current Understanding, Engineering, and Enabling Technologies.}, journal = {Chemical reviews}, volume = {123}, number = {1}, pages = {31-72}, pmid = {36317983}, issn = {1520-6890}, mesh = {Humans ; *Microbiota ; Technology ; }, abstract = {The human microbiome is composed of a collection of dynamic microbial communities that inhabit various anatomical locations in the body. Accordingly, the coevolution of the microbiome with the host has resulted in these communities playing a profound role in promoting human health. Consequently, perturbations in the human microbiome can cause or exacerbate several diseases. In this Review, we present our current understanding of the relationship between human health and disease development, focusing on the microbiomes found across the digestive, respiratory, urinary, and reproductive systems as well as the skin. We further discuss various strategies by which the composition and function of the human microbiome can be modulated to exert a therapeutic effect on the host. Finally, we examine technologies such as multiomics approaches and cellular reprogramming of microbes that can enable significant advancements in microbiome research and engineering.}, }
@article {pmid36315176, year = {2022}, author = {Sadekov, TS and Boyko, AN and Omarova, MA and Rogovskii, VS and Zhilenkova, OG and Zatevalov, AM and Mironov, AY}, title = {Evaluation of the structure of the human microbiome in multiple sclerosis by the concentrations of microbial markers in the blood.}, journal = {Klinicheskaia laboratornaia diagnostika}, volume = {67}, number = {10}, pages = {600-606}, doi = {10.51620/0869-2084-2022-67-10-600-606}, pmid = {36315176}, issn = {0869-2084}, support = {22-15-00284//The Russian Science Foundation/ ; }, mesh = {Humans ; *Multiple Sclerosis ; Plasmalogens ; *Microbiota ; Bacteria/genetics ; Endotoxins/analysis ; Biomarkers ; }, abstract = {The relationship between multiple sclerosis and the state of the human microbiome was studied, namely, the change in the representation of microbiota phylotypes, the proportion of coccal flora, the proportion of anaerobic, gram-negative, proteolytically active microflora, as well as the concentration of markers of bacterial plasmalogen and endotoxin in the blood. Microbiome studies were carried out by gas chromatography - mass spectrometry of microbial markers in the blood. A statistically significant increase in blood concentrations of the total level of microbial markers of bacterial plasmalogen and endotoxin was determined in multiple sclerosis, which may be associated with an increase in the permeability of the intestinal wall. In multiple sclerosis, the proportion of coccal, gram-negative, anaerobic microflora with a proteolytic type of metabolic activity increases. The correlations of the representation of microbiota phylotypes change due to the switching of the direct relationship Proteobacteria-Bacteroides to Proteobacteria-Firmicutes. In multiple sclerosis, Actinobacteria and Proteobacteria increase and Firmicutes decrease. Conclusion. The multiple sclerosis disease may be associated with pathological changes in the structure of the microbiome and the growth of endotoxemia, which may be one of the factors in the pathogenesis of the disease. New laboratory markers for diagnosing and predicting the course of MS have been proposed.}, }
@article {pmid36307422, year = {2022}, author = {Wang, Y and Jian, C}, title = {Sustainable plant-based ingredients as wheat flour substitutes in bread making.}, journal = {NPJ science of food}, volume = {6}, number = {1}, pages = {49}, pmid = {36307422}, issn = {2396-8370}, abstract = {Bread as a staple food has been predominantly prepared from refined wheat flour. The world's demand for food is rising with increased bread consumption in developing countries where climate conditions are unsuitable for wheat cultivation. This reliance on wheat increases the vulnerability to wheat supply shocks caused by force majeure or man-made events, in addition to negative environmental and health consequences. In this review, we discuss the contribution to the sustainability of food systems by partially replacing wheat flour with various types of plant ingredients in bread making, also known as composite bread. The sustainable sources of non-wheat flours, their example use in bread making and potential health and nutritional benefits are summarized. Non-wheat flours pose techno-functional challenges due to significantly different properties of their proteins compared to wheat gluten, and they often contain off-favor compounds that altogether limit the consumer acceptability of final bread products. Therefore, we detail recent advances in processing strategies to improve the sensory and nutritional profiles of composite bread. A special focus is laid on fermentation, for its accessibility and versatility to apply to different ingredients and scenarios. Finally, we outline research needs that require the synergism between sustainability science, human nutrition, microbiomics and food science.}, }
@article {pmid36301976, year = {2022}, author = {Armstrong, D and Dregan, A and Ashworth, M and White, P}, title = {Prior antibiotics and risk of subsequent Herpes zoster: A population-based case control study.}, journal = {PloS one}, volume = {17}, number = {10}, pages = {e0276807}, pmid = {36301976}, issn = {1932-6203}, mesh = {Humans ; Adolescent ; Young Adult ; Adult ; Middle Aged ; Child ; Herpesvirus 3, Human ; Case-Control Studies ; Anti-Bacterial Agents/adverse effects ; *Herpes Zoster ; *Chickenpox ; }, abstract = {BACKGROUND: The effect of antibiotics on the human microbiome is now well established, but their indirect effect on the related immune response is less clear. The possible association of Herpes zoster, which involves a reactivation of a previous varicella zoster virus infection, with prior antibiotic exposure might indicate a potential link with the immune response.<br><br>METHODS: A case-control study was carried out using a clinical database, the UK's Clinical Practice Research Datalink. A total of 163,754 patients with varicella zoster virus infection and 331,559 age/sex matched controls were identified and their antibiotic exposure over the previous 10 years, and longer when data permitted, was identified. Conditional logistic regression was used to identify the association between antibiotic exposure and subsequent infection in terms of volume and timing.<br><br>RESULTS: The study found an association of antibiotic prescription and subsequent risk of varicella zoster virus infection (adjusted odds ratio of 1.50; 95%CIs: 1.42-1.58). The strongest association was with a first antibiotic over 10 years ago (aOR: 1.92; 95%CIs: 1.88-1.96) which was particularly pronounced in the younger age group of 18 to 50 (aOR 2.77; 95%CIs: 1.95-3.92).<br><br>CONCLUSIONS: By finding an association between prior antibiotics and Herpes zoster this study has shown that antibiotics may be involved in the reactivation of the varicella zoster virus. That effect, moreover, may be relatively long term. This indirect effect of antibiotics on viruses, possibly mediated through their effect on the microbiome and immune system, merits further study.}, }
@article {pmid36301483, year = {2023}, author = {Pereira, GC}, title = {An Automated Strategy to Handle Antigenic Variability in Immunisation Protocols, Part I: Nanopore Sequencing of Infectious Agent Variants.}, journal = {Methods in molecular biology (Clifton, N.J.)}, volume = {2575}, number = {}, pages = {305-321}, pmid = {36301483}, issn = {1940-6029}, mesh = {Humans ; SARS-CoV-2/genetics ; *Nanopore Sequencing ; *COVID-19/prevention &amp; control ; Immunization ; Antigenic Variation ; RNA, Messenger ; *Zika Virus/genetics ; *Zika Virus Infection ; }, abstract = {Infectious agents often challenge therapeutics, from antibiotics resistance to antigenic variability affecting inoculation measures. Over the last decades, genome sequencing arose as an important ally to address such challenges. In bacterial infection, whole-genome-sequencing (WGS) supports tracking pathogenic alterations affecting the human microbiome. In viral infection, the analysis of the relevant sequence of nucleotides helps with determining historical variants of a virus and elucidates details about infection clusters and their distribution. Additionally, genome sequencing is now an important step in inoculation protocols, isolating target genes to design more robust immunisation assays. Ultimately, genetic engineering has empowered repurposing at scale, allowing long-lasting repeating clinical trials to be automated within a much shorter time-frame, by adjusting existing protocols. This is particularly important during sanitary emergencies as the ones caused by the 2014 West African Ebola outbreak, the Zika virus rapid spread in both South and North America in 2015, followed by Asia in 2016, and the pandemic caused by the SARS-CoV-2, which has infected more than 187 million people and caused more than 4 million deaths, worldwide, as per July 2021 statistics. In this scenery, this chapter presents a novel fully automated strategy to handle antigenic variability in immunisation protocols. The methodology comprises of two major steps (1) nanopore sequencing of infectious agent variants - the focus is on the SARS-CoV-2 and its variants; followed by (2) mRNA vector design for immunotherapy. This chapter presents the nanopore sequencing step and Chapter 17 introduces a protocol for mRNA vector design.}, }
@article {pmid36288274, year = {2022}, author = {France, MT and Brown, SE and Rompalo, AM and Brotman, RM and Ravel, J}, title = {Identification of shared bacterial strains in the vaginal microbiota of related and unrelated reproductive-age mothers and daughters using genome-resolved metagenomics.}, journal = {PloS one}, volume = {17}, number = {10}, pages = {e0275908}, pmid = {36288274}, issn = {1932-6203}, support = {R01 AI116799/AI/NIAID NIH HHS/United States ; R01 NR015495/NR/NINR NIH HHS/United States ; R01 AI060892/AI/NIAID NIH HHS/United States ; }, mesh = {Child ; Humans ; Female ; Adolescent ; *Microbiota/genetics ; Vagina/microbiology ; Reproduction ; Bacteria/genetics ; Metagenomics ; }, abstract = {It has been suggested that the human microbiome might be vertically transmitted from mother to offspring and that early colonizers may play a critical role in development of the immune system. Studies have shown limited support for the vertical transmission of the intestinal microbiota but the derivation of the vaginal microbiota remains largely unknown. Although the vaginal microbiota of children and reproductive age women differ in composition, the vaginal microbiota could be vertically transmitted. To determine whether there was any support for this hypothesis, we examined the vaginal microbiota of daughter-mother pairs from the Baltimore metropolitan area (ages 14-27, 32-51; n = 39). We assessed whether the daughter's microbiota was similar in composition to their mother's using metataxonomics. Permutation tests revealed that while some pairs did have similar vaginal microbiota, the degree of similarity did not exceed that expected by chance. Genome-resolved metagenomics was used to identify shared bacterial strains in a subset of the families (n = 22). We found a small number of bacterial strains that were shared between mother-daughter pairs but identified more shared strains between individuals from different families, indicating that vaginal bacteria may display biogeographic patterns. Earlier-in-life studies are needed to demonstrate vertical transmission of the vaginal microbiota.}, }
@article {pmid36287108, year = {2023}, author = {Ponziani, FR and Nesci, A and Caputo, C and Salvatore, L and Picca, A and Del Chierico, F and Paroni Sterbini, F and Marzetti, E and Di Giorgio, A and Santoro, L and Putignani, L and Gasbarrini, A and Santoliquido, A and Pompili, M}, title = {High prevalence of lower limb atherosclerosis is linked with the gut-liver axis in patients with primary biliary cholangitis.}, journal = {Liver international : official journal of the International Association for the Study of the Liver}, volume = {43}, number = {2}, pages = {370-380}, pmid = {36287108}, issn = {1478-3231}, mesh = {Humans ; Female ; *Liver Cirrhosis, Biliary/complications ; *Non-alcoholic Fatty Liver Disease/epidemiology/complications ; Tumor Necrosis Factor-alpha ; *Hypercholesterolemia/complications ; Prevalence ; Vascular Cell Adhesion Molecule-1 ; *Atherosclerosis/epidemiology/complications ; Lower Extremity ; }, abstract = {BACKGROUND AND AIMS: Hypercholesterolemia is frequent in people with primary biliary cholangitis (PBC); however, it does not seem to confer an increased risk of cardiovascular disease. We aimed to evaluate the prevalence of peripheral arterial disease in PBC women and its association with the gut-liver axis and systemic inflammation.<br><br>METHODS: Thirty patients affected by PBC and hypercholesterolemia were enrolled, with equal-sized groups of women with non-alcoholic fatty liver disease (NAFLD) and healthy controls (CTRL). All patients underwent Doppler ultrasound examination of peripheral arteries, assessment of flow-mediated dilation, quantification of circulating cytokines and vasoactive mediators and characterization of the gut microbiota.<br><br>RESULTS: PBC patients had a higher prevalence of lower extremity arterial disease (LEAD) defined as atherosclerotic plaques in any of femoral, popliteal and/or tibial arteries compared with both NAFLD and CTRL women (83.3% vs. 53.3% and 50%, respectively; p&#xa0;=&#x2009;.01). Factors associated with LEAD at univariate analysis were VCAM-1 (p&#xa0;=&#x2009;.002), ICAM-1 (p&#xa0;=&#x2009;.003), and TNF-alpha (p&#xa0;=&#x2009;.04) serum levels, but only VCAM-1 (OR 1.1, 95% CI 1.0-1.1; p&#xa0;=&#x2009;.04) and TNF-alpha (OR 1.12, 95% CI 0.99-1.26; p&#xa0;=&#x2009;.04) were confirmed as independent predictors in the multivariate model. Gut microbiota analysis revealed that Acidaminococcus (FDR&#xa0;=&#xa0;0.0008), Bifidobacterium (FDR&#xa0;=&#xa0;0.001) and Oscillospira (FDR&#xa0;=&#xa0;0.03) were differentially expressed among groups. Acidaminococcus, which was increased in PBC, was positively correlated with TNF-alpha serum levels. Down-regulation of metabolic pathways linked to fatty acid and butyrate metabolism, glyoxylate metabolism and branched-chain amino acids degradation was found in the functional gut metagenome of PBC women.<br><br>CONCLUSIONS: LEAD is common in patients affected by PBC and is associated with inflammatory markers and alterations in the gut-liver axis.}, }
@article {pmid36286197, year = {2022}, author = {Jones, RP and Ponomarenko, A}, title = {Roles for Pathogen Interference in Influenza Vaccination, with Implications to Vaccine Effectiveness (VE) and Attribution of Influenza Deaths.}, journal = {Infectious disease reports}, volume = {14}, number = {5}, pages = {710-758}, pmid = {36286197}, issn = {2036-7430}, abstract = {Pathogen interference is the ability of one pathogen to alter the course and clinical outcomes of infection by another. With up to 3000 species of human pathogens the potential combinations are vast. These combinations operate within further immune complexity induced by infection with multiple persistent pathogens, and by the role which the human microbiome plays in maintaining health, immune function, and resistance to infection. All the above are further complicated by malnutrition in children and the elderly. Influenza vaccination offers a measure of protection for elderly individuals subsequently infected with influenza. However, all vaccines induce both specific and non-specific effects. The specific effects involve stimulation of humoral and cellular immunity, while the nonspecific effects are far more nuanced including changes in gene expression patterns and production of small RNAs which contribute to pathogen interference. Little is known about the outcomes of vaccinated elderly not subsequently infected with influenza but infected with multiple other non-influenza winter pathogens. In this review we propose that in certain years the specific antigen mix in the seasonal influenza vaccine inadvertently increases the risk of infection from other non-influenza pathogens. The possibility that vaccination could upset the pathogen balance, and that the timing of vaccination relative to the pathogen balance was critical to success, was proposed in 2010 but was seemingly ignored. Persons vaccinated early in the winter are more likely to experience higher pathogen interference. Implications to the estimation of vaccine effectiveness and influenza deaths are discussed.}, }
@article {pmid36284711, year = {2022}, author = {Keren, R and Méheust, R and Santini, JM and Thomas, A and West-Roberts, J and Banfield, JF and Alvarez-Cohen, L}, title = {Global genomic analysis of microbial biotransformation of arsenic highlights the importance of arsenic methylation in environmental and human microbiomes.}, journal = {Computational and structural biotechnology journal}, volume = {20}, number = {}, pages = {559-572}, pmid = {36284711}, issn = {2001-0370}, support = {P42 ES004705/ES/NIEHS NIH HHS/United States ; }, abstract = {Arsenic is a ubiquitous toxic element, the global cycle of which is highly affected by microbial redox reactions and assimilation into organoarsenic compounds through sequential methylation reactions. While microbial biotransformation of arsenic has been studied for decades, the past years have seen the discovery of multiple new genes related to arsenic metabolism. Still, most studies focus on a small set of key genes or a small set of cultured microorganisms. Here, we leveraged the recently greatly expanded availability of microbial genomes of diverse organisms from lineages lacking cultivated representatives, including those reconstructed from metagenomes, to investigate genetic repertoires of taxonomic and environmental controls on arsenic metabolic capacities. Based on the collection of arsenic-related genes, we identified thirteen distinct metabolic guilds, four of which combine the aio and ars operons. We found that the best studied phyla have very different combinations of capacities than less well-studied phyla, including phyla lacking isolated representatives. We identified a distinct arsenic gene signature in the microbiomes of humans exposed or likely exposed to drinking water contaminated by arsenic and that arsenic methylation is important in soil and in human microbiomes. Thus, the microbiomes of humans exposed to arsenic have the potential to exacerbate arsenic toxicity. Finally, we show that machine learning can predict bacterial arsenic metabolism capacities based on their taxonomy and the environment from which they were sampled.}, }
@article {pmid36281758, year = {2024}, author = {Yadav, M and Chauhan, NS}, title = {Role of gut-microbiota in disease severity and clinical outcomes.}, journal = {Briefings in functional genomics}, volume = {23}, number = {1}, pages = {24-37}, doi = {10.1093/bfgp/elac037}, pmid = {36281758}, issn = {2041-2657}, mesh = {Humans ; *Gastrointestinal Microbiome ; Dysbiosis ; Diet ; Patient Acuity ; }, abstract = {A delicate balance of nutrients, antigens, metabolites and xenobiotics in body fluids, primarily managed by diet and host metabolism, governs human health. Human gut microbiota is a gatekeeper to nutrient bioavailability, pathogens exposure and xenobiotic metabolism. Human gut microbiota starts establishing during birth and evolves into a resilient structure by adolescence. It supplements the host's metabolic machinery and assists in many physiological processes to ensure health. Biotic and abiotic stressors could induce dysbiosis in gut microbiota composition leading to disease manifestations. Despite tremendous scientific advancements, a clear understanding of the involvement of gut microbiota dysbiosis during disease onset and clinical outcomes is still awaited. This would be important for developing an effective and sustainable therapeutic intervention. This review synthesizes the present scientific knowledge to present a comprehensive picture of the role of gut microbiota in the onset and severity of a disease.}, }
@article {pmid36280324, year = {2022}, author = {Gupta, A and Singh, V and Mani, I}, title = {Dysbiosis of human microbiome and infectious diseases.}, journal = {Progress in molecular biology and translational science}, volume = {192}, number = {1}, pages = {33-51}, doi = {10.1016/bs.pmbts.2022.06.016}, pmid = {36280324}, issn = {1878-0814}, mesh = {Humans ; Dysbiosis ; Prebiotics ; *Gastrointestinal Microbiome ; *Microbiota ; *Probiotics ; Bacteria ; *Communicable Diseases ; }, abstract = {Since birth, the human body gets colonized by various communities of symbiotic or commensal microorganisms and they persist till the death of an individual. The human microbiome is comprised of the genomes of microorganisms such as viruses, archaea, eukaryotes, protozoa, and, most remarkably, bacteria. The development of "omics" technologies gave way to the Human Microbiome Project (HMP) which aimed at exploring the collection of microbial genes and genomes inhabiting the human body. Eubiosis, i.e., a healthy and balanced composition of such microbes contributes to the metabolic function, protection against pathogens and provides nutrients and energy to the host. Whereas, an imbalance in the diversity of microorganisms, termed dysbiosis, greatly influences the state of health and disease. This chapter summarizes the impact of gut bacteria on the well-being of humans and highlights the protective role played by the human microbiota during bacterial and viral infections. The condition of dysbiosis and how it plays a role in the establishment of various infections and metabolic disorders such as Clostridioides difficile infection (CFI), inflammatory bowel disease (IBD), cancer, periodontitis, and obesity are described in detail. Further, treatments such as fecal transplantation, probiotics, prebiotics, phage therapy, and CRISPR/Cas system, which target gut microbiota during digestive diseases are also discussed.}, }
@article {pmid36280323, year = {2022}, author = {Ahrodia, T and Yodhaanjali, JR and Das, B}, title = {Vaginal microbiome dysbiosis in preterm birth.}, journal = {Progress in molecular biology and translational science}, volume = {192}, number = {1}, pages = {309-329}, doi = {10.1016/bs.pmbts.2022.08.001}, pmid = {36280323}, issn = {1878-0814}, mesh = {Infant, Newborn ; Pregnancy ; Female ; Humans ; *Premature Birth ; Dysbiosis ; RNA, Ribosomal, 16S/genetics ; *Microbiota ; Lactobacillus/genetics/metabolism ; Bacteria/metabolism ; Lactic Acid/metabolism ; }, abstract = {All the environmentally exposed surfaces of the human body harbor ecologically distinct microbial communities with a mutualistic beneficial relationship. Depending on the body sites, microbes may provide metabolic functions, protection against pathogens, and signaling molecules to modulate host physiology and reduce disease susceptibility. Our recent understanding of the vaginal microbiome based on culture-independent 16S rRNA gene sequencing indicates that Lactobacillus-dominated microbial communities of healthy women play an important role in decreasing susceptibility to several urogenital diseases, including bacterial, fungal and viral infections. The findings of shotgun sequencing of the vaginal microbiome suggest that microbial-derived lactic acid, bacteriostatic, bactericidal molecules, and lower vaginal pH mediate such protections and regulations. Bacterial species, the dominant component of the vaginal microbiome, also play a key role in determining the gestation period and birth outcomes of reproductive-age women. The presence of Lactobacillus crispatus species in the vaginal milieu reduces the risk of preterm delivery in women of Asian ancestry. A deeper knowledge of the vaginal microbiota's role in the succession and development of newborn gut bacteria would also be beneficial. The microbiome of the mother changes throughout pregnancy and is linked to the microbiome of the newborn. This chapter highlights updated information and new opportunities for human microbiome research, focusing on the assessment of the risk of preterm birth.}, }
@article {pmid36280321, year = {2022}, author = {Alam, MJ and Puppala, V and Uppulapu, SK and Das, B and Banerjee, SK}, title = {Human microbiome and cardiovascular diseases.}, journal = {Progress in molecular biology and translational science}, volume = {192}, number = {1}, pages = {231-279}, doi = {10.1016/bs.pmbts.2022.07.012}, pmid = {36280321}, issn = {1878-0814}, mesh = {Humans ; *Cardiovascular Diseases ; Dysbiosis ; *Gastrointestinal Microbiome ; Bacteria ; Inflammation/complications ; }, abstract = {A number of microorganisms are co-evolved with the host, among which bacteria are the predominant organisms in the colonic site. The human microbiota contributes to various physiological functions, including the digestion and degradation of food components, harvesting of inaccessible nutrients, immune system regulation, maintenance of gut barrier function, and regulation of brain function and behavior. Microbes in the gut produce a wealth of metabolites from the exogenous dietary substances or endogenous metabolic compounds produced by the host and the resident microorganisms. These microbial-derived metabolites are the major factors in the host-microbiota cross-talk and influence the host's cardiometabolic health directly or indirectly depending on the structure and function of the microbial community. Evidence suggests that the perturbation in the composition and function of gut microbiota (referred to as gut dysbiosis) is associated with the development of several diseased conditions such as that of the gastrointestinal tract or colorectal cancer, metabolic diseases such as obesity, diabetes, immune disorders e.g. asthma, allergies, depression, anxiety and cardiometabolic disease. Several pathological conditions in the gastrointestinal tract may impair the intestinal barrier that allows translocation of bacteria and their metabolites to a remote organ such as the heart, which may ultimately be associated with systemic inflammation and the development of CVDs. In this chapter, we will discuss various gut microbiota-dependent metabolites, which have a significant role in cardiovascular diseases' pathologic processes and their risk factors. Finally, we will discuss the therapeutic potential of the gut-metabolite-heart axis as a novel target for the treatment of CVD and highlight the current updates and exciting directions for future research.}, }
@article {pmid36279192, year = {2023}, author = {Nguyen, NA and Huang, X and Cabrera, LE and Pekkarinen, PT and Nowlan, K and Strandin, T and Kantele, A and Vapalahti, O and Heinonen, S and Kekäläinen, E}, title = {A comprehensive assessment of four whole blood stabilizers for flow-cytometric analysis of leukocyte populations.}, journal = {Cytometry. Part A : the journal of the International Society for Analytical Cytology}, volume = {103}, number = {4}, pages = {313-324}, doi = {10.1002/cyto.a.24700}, pmid = {36279192}, issn = {1552-4930}, support = {323499//Academy of Finland/ ; //Lastentautien Tutkimuss&#xe4;&#xe4;ti&#xf6;/ ; //Sigrid Jus&#xe9;liuksen S&#xe4;&#xe4;ti&#xf6;/ ; //Suomen L&#xe4;&#xe4;ketieteen S&#xe4;&#xe4;ti&#xf6;/ ; }, mesh = {Humans ; Flow Cytometry ; *Proteomics ; *COVID-19 ; Leukocytes ; Granulocytes ; }, abstract = {Though cryopreservation of cell fractions is widely used in flow cytometry studies, whole blood cryopreservation is more challenging due to the presence of erythrocytes and effects of fixatives commonly used for preservation. Here, we evaluated and compared head-to-head the performance of four commercial whole blood cryopreservation kits; (1) Cytodelics, (2) Stable-Lyse V2 and Stable-Store V2 (SLSS-V2), (3) Proteomic stabilizer (PROT-1), and (4) Transfix. We found that PROT-1, Transfix, and Cytodelics maintained the distribution of major leukocyte subsets-granulocytes, T cells, natural killer cells, and B cells, on a comparable level to unpreserved samples, despite the attenuation of fluorescence intensities in flow cytometric assays. Moreover, these three stabilizers also maintained the activated phenotypes of neutrophils upon stimulation with N-formylmethionyl-leucyl-phenylalanine and lipopolysaccharides. The upregulation of adhesion molecules (CD11b), Fc receptors (CD16), and granule proteins (CD66b), as well as the shedding of surface L-selectin (CD62L), was conserved most efficiently in PROT-1 and Cytodelics when compared to samples only treated with erythrocyte lysing. However, none of the stabilizers provided a reliable detection of CCR7 for accurate quantification of T cell maturation stages. We also evaluated the performance of Cytodelics in longitudinal clinical samples obtained from acute COVID-19 patients, where it allowed reliable detection of lymphopenia and granulocyte expansion. These results support the feasibility of whole blood cryopreservation for immunophenotyping by flow cytometry, particularly in longitudinal studies. In conclusion, the performance of different stabilizers is variable and therefore the choice of stabilizers should depend on cell type of interest, as well as antibody clones and experimental design of each study.}, }
@article {pmid36278460, year = {2022}, author = {Suryaletha, K and Savithri, AV and Nayar, SA and Asokan, S and Rajeswary, D and Thomas, S}, title = {Demystifying Bacteriocins of Human Microbiota by Genome Guided Prospects: An Impetus to Rekindle the Antimicrobial Research.}, journal = {Current protein &amp; peptide science}, volume = {23}, number = {12}, pages = {811-822}, pmid = {36278460}, issn = {1875-5550}, mesh = {Humans ; *Bacteriocins/genetics/pharmacology ; Anti-Bacterial Agents/pharmacology ; *Microbiota ; Bacteria/genetics ; }, abstract = {The human microbiome is a reservoir of potential bacteriocins that can counteract multidrug resistant bacterial pathogens. Unlike antibiotics, bacteriocins selectively inhibit a spectrum of competent bacteria and are said to safeguard gut commensals, reducing the chance of dysbiosis. Bacteriocinogenic probiotics or bacteriocins of human origin will be more pertinent in human physiological conditions for therapeutic applications to act against invading pathogens. Recent advancement in the omics approach enables the mining of diverse and novel bacteriocins by identifying biosynthetic gene clusters from the human microbial genome, pangenome or shotgun metagenome, which is a breakthrough in the discovery line of novel bacteriocins. This review summarizes the most recent trends and therapeutic potential of bacteriocins of human microbial origin, the advancement in the in silico algorithms and databases in the discovery of novel bacteriocin, and how to bridge the gap between the discovery of bacteriocin genes from big datasets and their in vitro production. Besides, the later part of the review discussed the various impediments in their clinical applications and possible solution to bring them into the frontline therapeutics to control infections, thereby meeting the challenges of global antimicrobial resistance.}, }
@article {pmid36274732, year = {2022}, author = {Matharu, D and Ponsero, AJ and Dikareva, E and Korpela, K and Kolho, KL and de Vos, WM and Salonen, A}, title = {Bacteroides abundance drives birth mode dependent infant gut microbiota developmental trajectories.}, journal = {Frontiers in microbiology}, volume = {13}, number = {}, pages = {953475}, pmid = {36274732}, issn = {1664-302X}, abstract = {BACKGROUND AND AIMS: Birth mode and other early life factors affect a newborn's microbial colonization with potential long-term health effects. Individual variations in early life gut microbiota development, especially their effects on the functional repertoire of microbiota, are still poorly characterized. This study aims to provide new insights into the gut microbiome developmental trajectories during the first year of life.<br><br>METHODS: Our study comprised 78 term infants sampled at 3 weeks, 3 months, 6 months, and 12 months (n = 280 total samples), and their mothers were sampled in late pregnancy (n = 50). Fecal DNA was subjected to shotgun metagenomic sequencing. Infant samples were studied for taxonomic and functional maturation, and maternal microbiota was used as a reference. Hierarchical clustering on taxonomic profiles was used to identify the main microbiota developmental trajectories in the infants, and their associations with perinatal and postnatal factors were assessed.<br><br>RESULTS: In line with previous studies, infant microbiota composition showed increased alpha diversity and decreased beta diversity by age, converging toward an adult-like profile. However, we did not observe an increase in functional alpha diversity, which was stable and comparable with the mother samples throughout all the sampling points. Using a de novo clustering approach, two main infant microbiota clusters driven by Bacteroidaceae and Clostridiaceae emerged at each time point. The clusters were associated with birth mode and their functions differed mainly in terms of biosynthetic and carbohydrate degradation pathways, some of which consistently differed between the clusters for all the time points. The longitudinal analysis indicated three main microbiota developmental trajectories, with the majority of the infants retaining their characteristic cluster until 1 year. As many as 40% of vaginally delivered infants were grouped with infants delivered by C-section due to their clear and persistent depletion in Bacteroides. Intrapartum antibiotics, any perinatal or postnatal factors, maternal microbiota composition, or other maternal factors did not explain the depletion in Bacteroides in the subset of vaginally born infants.<br><br>CONCLUSION: Our study provides an enhanced understanding of the compositional and functional early life gut microbiota trajectories, opening avenues for investigating elusive causes that influence non-typical microbiota development.}, }
@article {pmid36274714, year = {2022}, author = {Zheng, Y and Shi, J and Chen, Q and Deng, C and Yang, F and Wang, Y}, title = {Identifying individual-specific microbial DNA fingerprints from skin microbiomes.}, journal = {Frontiers in microbiology}, volume = {13}, number = {}, pages = {960043}, pmid = {36274714}, issn = {1664-302X}, abstract = {Skin is an important ecosystem that links the human body and the external environment. Previous studies have shown that the skin microbial community could remain stable, even after long-term exposure to the external environment. In this study, we explore two questions: Do there exist strains or genetic variants in skin microorganisms that are individual-specific, temporally stable, and body site-independent? And if so, whether such microorganismal genetic variants could be used as markers, called "fingerprints" in our study, to identify donors? We proposed a framework to capture individual-specific DNA microbial fingerprints from skin metagenomic sequencing data. The fingerprints are identified on the frequency of 31-mers free from reference genomes and sequence alignments. The 616 metagenomic samples from 17 skin sites at 3-time points from 12 healthy individuals from Integrative Human Microbiome Project were adopted. Ultimately, one contig for each individual is assembled as a fingerprint. And results showed that 89.78% of the skin samples despite body sites could identify their donors correctly. It is observed that 10 out of 12 individual-specific fingerprints could be aligned to Cutibacterium acnes. Our study proves that the identified fingerprints are temporally stable, body site-independent, and individual-specific, and can identify their donors with enough accuracy. The source code of the genetic identification framework is freely available at https://github.com/Ying-Lab/skin_fingerprint.}, }
@article {pmid36271144, year = {2023}, author = {Zhang, F and Lau, RI and Liu, Q and Su, Q and Chan, FKL and Ng, SC}, title = {Gut microbiota in COVID-19: key microbial changes, potential mechanisms and clinical applications.}, journal = {Nature reviews. Gastroenterology &amp; hepatology}, volume = {20}, number = {5}, pages = {323-337}, pmid = {36271144}, issn = {1759-5053}, mesh = {Humans ; *COVID-19 ; SARS-CoV-2 ; *Gastrointestinal Microbiome ; Gastrointestinal Tract ; *Microbiota ; }, abstract = {The gastrointestinal tract is involved in coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The gut microbiota has important roles in viral entry receptor angiotensin-converting enzyme 2 (ACE2) expression, immune homeostasis, and crosstalk between the gut and lungs, the 'gut-lung axis'. Emerging preclinical and clinical studies indicate that the gut microbiota might contribute to COVID-19 pathogenesis and disease outcomes; SARS-CoV-2 infection was associated with altered intestinal microbiota and correlated with inflammatory and immune responses. Here, we discuss the cutting-edge evidence on the interactions between SARS-CoV-2 infection and the gut microbiota, key microbial changes in relation to COVID-19 severity and host immune dysregulations with the possible underlying mechanisms, and the conceivable consequences of the pandemic on the human microbiome and post-pandemic health. Finally, potential modulatory strategies of the gut microbiota are discussed. These insights could shed light on the development of microbiota-based interventions for COVID-19.}, }
@article {pmid36270683, year = {2022}, author = {Mahapatra, S and Mohanty, S and Mishra, R and Prasad, P}, title = {An overview of cancer and the human microbiome.}, journal = {Progress in molecular biology and translational science}, volume = {191}, number = {1}, pages = {83-139}, doi = {10.1016/bs.pmbts.2022.07.007}, pmid = {36270683}, issn = {1878-0814}, mesh = {Humans ; *Microbiota ; Symbiosis ; *Neoplasms ; }, abstract = {Mutual beneficial associations with the microbial consortia are an essential requisite of human life. Microbial communities have both a symbiotic and a pathogenic standpoint, which portrays a context-dependent scenario of the human microbiome. The symbiotic assemblage works to develop indispensable functions of the human body such as immune system, digestive system, defense against colonization by pathobionts and their toxins, etc. Furthermore, any deviation in the resource utilization by the symbionts due to host factors comprising lifestyle changes, diet, drugs, immunocompromised states, and co-morbidities could perturb beneficial microbes communities and promote the invasion by opportunistic pathogens thus, disrupting the homeostatic state. Microbial infestations have proved to be carcinogenic but this does not spontaneously establish a cancer hallmark, rather they initiate a cascade of events that disturbs the normal cellular activities finally these defective machineries invade distant sites of the body, submitting to a devastative transformed internal milieu. Significant technological and system biology advances have been made in elucidating a lucid but complex basis of such microbe-associated malignancies. This chapter discusses the recent advances, without compromising the concepts of the inception studies, including a brief version of the microbial status in cancer generation, mechanistic approaches adapted, therapeutic interventions, system biology approaches with special mention on the study design gaps, challenges in addressing the drawbacks and finally with a perspective of the future targeted studies, has been a focus of this piece of work.}, }
@article {pmid36270682, year = {2022}, author = {Ahrodia, T and Das, S and Bakshi, S and Das, B}, title = {Structure, functions, and diversity of the healthy human microbiome.}, journal = {Progress in molecular biology and translational science}, volume = {191}, number = {1}, pages = {53-82}, doi = {10.1016/bs.pmbts.2022.07.003}, pmid = {36270682}, issn = {1878-0814}, mesh = {Humans ; *Microbiota ; Bacteria/genetics ; Metagenome ; *Gastrointestinal Microbiome ; Archaea ; }, abstract = {Taxonomic composition and functional potency of microbes associated with different parts of the human body have largely been explored by culture-independent metagenome sequencing. The diverse microbiota living throughout the human body is made up of thousands of microbial taxa from all three domains of life: Archaea, Bacteria, and Eukarya. Microbial load and functional potency in different body sites are well distinct and have minimal resemblance at higher taxonomic levels between the two habitats. The highest microbial load, diversity, and functional potency including biosynthesis of essential nutrients, chemical modifications of dietary components, and sources of immunomodulatory molecules, are found in the gut microbiome. However, the inter-individual diversity and dynamics of the human microbiome in a given body habitat vary greatly over time. Both environmental factors and host genetics contribute significantly to shaping microbial community structure and its stability. A basic understanding of native microbial compositions and their functional potency and stability in different parts of healthy humans living across geography will help us to identify disease-specific microbiota and develop potential microbiome-based therapeutics. Here, we updated our current understanding of the diversity, dynamics, and functional potency of microbiomes associated with different parts of the human body.}, }
@article {pmid36270681, year = {2022}, author = {Ghosh, TS and Das, M}, title = {Emerging tools for understanding the human microbiome.}, journal = {Progress in molecular biology and translational science}, volume = {191}, number = {1}, pages = {29-51}, doi = {10.1016/bs.pmbts.2022.06.027}, pmid = {36270681}, issn = {1878-0814}, mesh = {Humans ; *High-Throughput Nucleotide Sequencing/methods ; *Microbiota ; Metagenome ; Metagenomics/methods ; Computational Biology/methods ; }, abstract = {Recent advances in sequencing technologies, experimental protocols and approaches in data generation and analysis have enabled us to investigate the human microbiome at an unprecedented level of resolution. The current chapter aims to provide an understanding of the different computational and bioinformatic strategies adopted to answer the different questions of a typical microbiome investigation and how the upstream DNA sequencing methodologies can affect this. The chapter enlist the state-of-the-art in metagenomic data analysis along with the available strategies to perform an integrated investigation of the human microbiome along with other data layers.}, }
@article {pmid36270680, year = {2022}, author = {Pant, A and Das, B}, title = {Microbiome-based therapeutics: Opportunity and challenges.}, journal = {Progress in molecular biology and translational science}, volume = {191}, number = {1}, pages = {229-262}, doi = {10.1016/bs.pmbts.2022.07.006}, pmid = {36270680}, issn = {1878-0814}, mesh = {Humans ; *Microbiota ; *Probiotics ; }, abstract = {The autochthonous microbial communities comprising symbionts, commensals, and opportunistic pathogens living throughout the human body profoundly contribute to health by reducing disease susceptibility and maturing host immunity. The community compositions and functional repertoires of microbiomes present in the different body habitats are dynamic. The structural and functional balance of the human microbiome could be modulated by environmental factors, lifestyle, and host genetics. Several functions of the microbial community directly or indirectly modulate host cellular signaling pathways that are associated with energy assimilation, sensing and responding to environmental signals through the neuroendocrine pathways, and resistance against colonization of allochthonous microbiota with disease-causing potential. Both culture-dependent and independent characterizations of microbial community compositions and their functional attributes help us to recognize the importance of microbial diversity in individual's health and identify the microbes and their metabolites associated with health and diseases. Such an in-depth understanding of the human microbiome created avenues of microbiome-based translation research, which led to the discovery and development of large numbers of medical therapies. In this chapter, we discuss the current success of microbiome-based therapies for infectious and metabolic diseases, and the major bottleneck and challenges of translational research with the community of symbiotic microorganisms.}, }
@article {pmid36270674, year = {2022}, author = {Das, B}, title = {An introduction to human microbiome.}, journal = {Progress in molecular biology and translational science}, volume = {191}, number = {1}, pages = {1-28}, doi = {10.1016/bs.pmbts.2022.06.026}, pmid = {36270674}, issn = {1878-0814}, mesh = {Humans ; *Microbiota ; Dysbiosis ; Bacteria ; Archaea ; Host Microbial Interactions ; }, abstract = {The microbiome is an assemblage of a complex community of microbes (bacteria, archaea, fungi, algae, protists, and viruses) and their biomolecules occupying a well-defined habitat in or on a living or non-living object. All the environmentally exposed surfaces of the human body are colonized with trillions of microbes from all three major domains of life, including bacteria, archea, and microscopic eukarya. However, the richness, abundance, and functional potency of microbial taxa living in different parts of the human body are distinct. The Presence of common microbial taxa in different body habitats is also very rare. With the recent development of next generation sequencing technologies, it has been established that the indigenous microbial community in the human body and their functional attributes within a given body habitat vary over time, between ethnic groups and health status of the host. Perturbation of homeostasis in community structures or functions due to any extrinsic factors can alter mutualistic host-microbe interactions and may lead to disease. In addition, the dysbiotic state of the microbiome can also affect the efficacy of therapeutics, prolong treatment duration and lead to undesired treatment outcomes. In this chapter, structure, functions, diversity and dynamics of human microbiome in health and diseases, factors that alter microbial composition, interactions between microbial taxa and xenobiotics, and therapeutic efficacy of drugs in dysbiotic conditions are highlighted.}, }
@article {pmid36268225, year = {2022}, author = {Khorsand, B and Asadzadeh Aghdaei, H and Nazemalhosseini-Mojarad, E and Nadalian, B and Nadalian, B and Houri, H}, title = {Overrepresentation of Enterobacteriaceae and Escherichia coli is the major gut microbiome signature in Crohn's disease and ulcerative colitis; a comprehensive metagenomic analysis of IBDMDB datasets.}, journal = {Frontiers in cellular and infection microbiology}, volume = {12}, number = {}, pages = {1015890}, pmid = {36268225}, issn = {2235-2988}, mesh = {Humans ; *Colitis, Ulcerative ; *Crohn Disease/microbiology ; *Gastrointestinal Microbiome/genetics ; Metagenome ; Escherichia coli ; Siderophores ; Lipopolysaccharides ; *Inflammatory Bowel Diseases/microbiology ; Feces/microbiology ; *Escherichia coli Infections ; Sulfur ; Nitrogen ; }, abstract = {OBJECTIVES: A number of converging strands of research suggest that the intestinal Enterobacteriaceae plays a crucial role in the development and progression of inflammatory bowel disease (IBD), however, the changes in the abundance of Enterobacteriaceae species and their related metabolic pathways in Crohn's disease (CD) and ulcerative colitis (UC) compared to healthy people are not fully explained by comprehensive comparative metagenomics analysis. In the current study, we investigated the alternations of the Enterobacterales population in the gut microbiome of patients with CD and UC compared to healthy subjects.<br><br>METHODS: Metagenomic datasets were selected from the Integrative Human Microbiome Project (HMP2) through the Inflammatory Bowel Disease Multi'omics Database (IBDMDB). We performed metagenome-wide association studies on fecal samples from 191 CD patients, 132 UC patients, and 125 healthy controls (HCs). We used the metagenomics dataset to study bacterial community structure, relative abundance, differentially abundant bacteria, functional analysis, and Enterobacteriaceae-related biosynthetic pathways.<br><br>RESULTS: Compared to the gut microbiome of HCs, six Enterobacteriaceae species were significantly elevated in both CD and UC patients, including Escherichia coli, Klebsiella variicola, Klebsiella quasipneumoniae, Klebsiella pneumoniae, Proteus mirabilis, Citrobacter freundii, and Citrobacter youngae, while Klebsiella oxytoca, Morganella morganii, and Citrobacter amalonaticus were uniquely differentially abundant and enriched in the CD cohort. Four species were uniquely differentially abundant and enriched in the UC cohort, including Citrobacter portucalensis, Citrobacter pasteurii, Citrobacter werkmanii, and Proteus hauseri. Our analysis also showed a dramatically increased abundance of E. coli in their intestinal bacterial community. Biosynthetic pathways of aerobactin siderophore, LPS, enterobacterial common antigen, nitrogen metabolism, and sulfur relay systems encoded by E. coli were significantly elevated in the CD samples compared to the HCs. Menaquinol biosynthetic pathways were associated with UC that belonged to K. pneumoniae strains.<br><br>CONCLUSIONS: In conclusion, compared with healthy people, the taxonomic and functional composition of intestinal bacteria in CD and UC patients was significantly shifted to Enterobacteriaceae species, mainly E. coli and Klebsiella species.}, }
@article {pmid36266277, year = {2022}, author = {Sauvaitre, T and Van Landuyt, J and Durif, C and Roussel, C and Sivignon, A and Chalancon, S and Uriot, O and Van Herreweghen, F and Van de Wiele, T and Etienne-Mesmin, L and Blanquet-Diot, S}, title = {Role of mucus-bacteria interactions in Enterotoxigenic Escherichia coli (ETEC) H10407 virulence and interplay with human microbiome.}, journal = {NPJ biofilms and microbiomes}, volume = {8}, number = {1}, pages = {86}, pmid = {36266277}, issn = {2055-5008}, mesh = {Humans ; *Enterotoxigenic Escherichia coli/physiology ; Interleukin-8/genetics ; Virulence ; Diarrhea ; Caco-2 Cells ; *Escherichia coli Infections/microbiology ; Travel ; *Microbiota ; Bacteria ; Mucus ; Mucins ; }, abstract = {The intestinal mucus layer has a dual role in human health constituting a well-known microbial niche that supports gut microbiota maintenance but also acting as a physical barrier against enteric pathogens. Enterotoxigenic Escherichia coli (ETEC), the major agent responsible for traveler's diarrhea, is able to bind and degrade intestinal mucins, representing an important but understudied virulent trait of the pathogen. Using a set of complementary in vitro approaches simulating the human digestive environment, this study aimed to describe how the mucus microenvironment could shape different aspects of the human ETEC strain H10407 pathophysiology, namely its survival, adhesion, virulence gene expression, interleukin-8 induction and interactions with human fecal microbiota. Using the TNO gastrointestinal model (TIM-1) simulating the physicochemical conditions of the human upper gastrointestinal (GI) tract, we reported that mucus secretion and physical surface sustained ETEC survival, probably by helping it to face GI stresses. When integrating the host part in Caco2/HT29-MTX co-culture model, we demonstrated that mucus secreting-cells favored ETEC adhesion and virulence gene expression, but did not impede ETEC Interleukin-8 (IL-8) induction. Furthermore, we proved that mucosal surface did not favor ETEC colonization in a complex gut microbial background simulated in batch fecal experiments. However, the mucus-specific microbiota was widely modified upon the ETEC challenge suggesting its role in the pathogen infectious cycle. Using multi-targeted in vitro approaches, this study supports the major role played by mucus in ETEC pathophysiology, opening avenues in the design of new treatment strategies.}, }
@article {pmid36264944, year = {2022}, author = {Mäenpää, K and Wang, S and Ilves, M and El-Nezami, H and Alenius, H and Sinkko, H and Karisola, P}, title = {Skin microbiota of oxazolone-induced contact hypersensitivity mouse model.}, journal = {PloS one}, volume = {17}, number = {10}, pages = {e0276071}, pmid = {36264944}, issn = {1932-6203}, mesh = {Mice ; Animals ; Oxazolone ; RNA, Ribosomal, 16S/genetics ; Olive Oil ; Acetone ; *Microbiota ; Disease Models, Animal ; *Dermatitis, Allergic Contact ; Inflammation ; Bacteria ; }, abstract = {Contact allergy is a common skin allergy, which can be studied utilising contact hypersensitivity (CHS) animal model. However, it is not clear, whether CHS is a suitable model to investigate skin microbiota interactions. We characterised the effect of contact dermatitis on the skin microbiota and studied the biological effects of oxazolone (OXA) -induced inflammation on skin thickness, immune cell numbers and changes of the microbiota in CHS mouse model (n = 72) for 28 days. Through 16S rRNA gene sequencing we defined the composition of bacterial communities and associations of bacteria with inflammation. We observed that the vehicle solution of acetone and olive oil induced bacterial community changes on day 1, and OXA-induced changes were observed mainly on day 7. Many of the notably enriched bacteria present in the OXA-challenged positive group represented the genus Faecalibaculum which were most likely derived from the cage environment. Additionally, skin inflammation correlated negatively with Streptococcus, which is considered a native skin bacterium, and positively with Muribacter muris, which is typical in oral environment. Skin inflammation favoured colonisation of cage-derived faecal bacteria, and additionally mouse grooming transferred oral bacteria on the skin. Due to the observed changes, we conclude that CHS model could be used for certain skin microbiome-related research set-ups. However, since vehicle exposure can alter the skin microbiome as such, future studies should include considerations such as careful control sampling and statistical tests to account for potential confounding factors.}, }
@article {pmid36261456, year = {2022}, author = {Moitinho-Silva, L and Degenhardt, F and Rodriguez, E and Emmert, H and Juzenas, S and Möbus, L and Uellendahl-Werth, F and Sander, N and Baurecht, H and Tittmann, L and Lieb, W and Gieger, C and Peters, A and Ellinghaus, D and Bang, C and Franke, A and Weidinger, S and Rühlemann, MC}, title = {Host genetic factors related to innate immunity, environmental sensing and cellular functions are associated with human skin microbiota.}, journal = {Nature communications}, volume = {13}, number = {1}, pages = {6204}, pmid = {36261456}, issn = {2041-1723}, mesh = {Humans ; Genome-Wide Association Study ; *Microbiota/genetics ; Skin ; Immunity, Innate/genetics ; *Gastrointestinal Microbiome/genetics ; }, abstract = {Despite the increasing knowledge about factors shaping the human microbiome, the host genetic factors that modulate the skin-microbiome interactions are still largely understudied. This contrasts with recent efforts to characterize host genes that influence the gut microbiota. Here, we investigated the effect of genetics on skin microbiota across three different skin microenvironments through meta-analyses of genome-wide association studies (GWAS) of two population-based German cohorts. We identified 23 genome-wide significant loci harboring 30 candidate genes involved in innate immune signaling, environmental sensing, cell differentiation, proliferation and fibroblast activity. However, no locus passed the strict threshold for study-wide significance (P < 6.3 × 10[-10] for 80 features included in the analysis). Mendelian randomization (MR) analysis indicated the influence of staphylococci on eczema/dermatitis and suggested modulating effects of the microbiota on other skin diseases. Finally, transcriptional profiles of keratinocytes significantly changed after in vitro co-culturing with Staphylococcus epidermidis, chosen as a representative of skin commensals. Seven candidate genes from the GWAS were found overlapping with differential expression in the co-culturing experiments, warranting further research of the skin commensal and host genetic makeup interaction.}, }
@article {pmid36258167, year = {2022}, author = {Vikramdeo, KS and Anand, S and Pierce, JY and Singh, AP and Singh, S and Dasgupta, S}, title = {Distribution of microbiota in cervical preneoplasia of racially disparate populations.}, journal = {BMC cancer}, volume = {22}, number = {1}, pages = {1074}, pmid = {36258167}, issn = {1471-2407}, support = {R01 CA224306/CA/NCI NIH HHS/United States ; R01 CA231925/CA/NCI NIH HHS/United States ; CA231925, CA224306/NH/NIH HHS/United States ; }, mesh = {Female ; Humans ; Papillomaviridae/genetics ; RNA, Ribosomal, 16S/genetics ; *Papillomavirus Infections/complications ; Dysbiosis ; *Uterine Cervical Neoplasms/pathology ; *Microbiota/genetics ; *Uterine Cervical Dysplasia/epidemiology ; }, abstract = {BACKGROUNDS: Microbiome dysbiosis is an important contributing factor in tumor development and thus may be a risk predictor for human malignancies. In the United States, women with Hispanic/Latina (HIS) and African American (AA) background have a higher incidence of cervical cancer and poorer outcomes than Caucasian American (CA) women.<br><br>METHODS: Here, we assessed the distribution pattern of microbiota in cervical intraepithelial neoplasia (CIN) lesions obtained from HIS (n&#x2009;=&#x2009;12), AA (n&#x2009;=&#x2009;12), and CA (n&#x2009;=&#x2009;12) women, who were screened for CC risk assessment. We employed a 16S rRNA gene sequencing approach adapted from the NIH-Human Microbiome Project to identify the microbial niche in all CIN lesions (n&#x2009;=&#x2009;36).<br><br>RESULTS: We detected an appreciably decreased abundance of beneficial Lactobacillus in the CIN lesions of the AA and HIS women compared to the CA women. Differential abundance of potentially pathogenic Prevotella, Delftia, Gardnerella, and Fastidiosipila was also evident among the various racial groups. An increased abundance of Micrococcus was also evident in AA and HIS women compared to the CA women. The detection level of Rhizobium was higher among the AA ad CA women compared to the HIS women. In addition to the top 10 microbes, a unique niche of 27 microbes was identified exclusively in women with a histopathological diagnosis of CIN. Among these microbes, a group of 8 microbiota; Rubellimicrobium, Podobacter, Brevibacterium, Paracoccus, Atopobium, Brevundimonous, Comamonous, and Novospingobium was detected only in the CIN lesions obtained from AA and CA women.<br><br>CONCLUSIONS: Microbial dysbiosis in the cervical epithelium represented by an increased ratio of potentially pathogenic to beneficial microbes may be associated with increased CC risk disparities. Developing a race-specific reliable panel of microbial markers could be beneficial for CC risk assessment, disease prevention, and/or therapeutic guidance.}, }
@article {pmid36250060, year = {2022}, author = {Monshizadeh, M and Zomorodi, S and Mortensen, K and Ye, Y}, title = {Revealing bacteria-phage interactions in human microbiome through the CRISPR-Cas immune systems.}, journal = {Frontiers in cellular and infection microbiology}, volume = {12}, number = {}, pages = {933516}, pmid = {36250060}, issn = {2235-2988}, support = {R01 AI108888/AI/NIAID NIH HHS/United States ; R01 AI143254/AI/NIAID NIH HHS/United States ; }, mesh = {Bacteria/genetics ; *Bacteriophages/genetics ; CRISPR-Cas Systems ; Humans ; Immune System ; *Microbiota/genetics ; }, abstract = {The human gut microbiome is composed of a diverse consortium of microorganisms. Relatively little is known about the diversity of the bacteriophage population and their interactions with microbial organisms in the human microbiome. Due to the persistent rivalry between microbial organisms (hosts) and phages (invaders), genetic traces of phages are found in the hosts' CRISPR-Cas adaptive immune system. Mobile genetic elements (MGEs) found in bacteria include genetic material from phage and plasmids, often resultant from invasion events. We developed a computational pipeline (BacMGEnet), which can be used for inference and exploratory analysis of putative interactions between microbial organisms and MGEs (phages and plasmids) and their interaction network. Given a collection of genomes as the input, BacMGEnet utilizes computational tools we have previously developed to characterize CRISPR-Cas systems in the genomes, which are then used to identify putative invaders from publicly available collections of phage/prophage sequences. In addition, BacMGEnet uses a greedy algorithm to summarize identified putative interactions to produce a bacteria-MGE network in a standard network format. Inferred networks can be utilized to assist further examination of the putative interactions and for discovery of interaction patterns. Here we apply the BacMGEnet pipeline to a few collections of genomic/metagenomic datasets to demonstrate its utilities. BacMGEnet revealed a complex interaction network of the Phocaeicola vulgatus pangenome with its phage invaders, and the modularity analysis of the resulted network suggested differential activities of the different P. vulgatus' CRISPR-Cas systems (Type I-C and Type II-C) against some phages. Analysis of the phage-bacteria interaction network of human gut microbiome revealed a mixture of phages with a broad host range (resulting in large modules with many bacteria and phages), and phages with narrow host range. We also showed that BacMGEnet can be used to infer phages that invade bacteria and their interactions in wound microbiome. We anticipate that BacMGEnet will become an important tool for studying the interactions between bacteria and their invaders for microbiome research.}, }
@article {pmid36241544, year = {2022}, author = {Sánchez-Manubens, J and Henares, D and Muñoz-Almagro, C and Brotons de Los Reyes, P and Timoneda, N and Antón, J}, title = {Characterization of the nasopharyngeal microbiome in patients with Kawasaki disease.}, journal = {Anales de pediatria}, volume = {97}, number = {5}, pages = {300-309}, doi = {10.1016/j.anpede.2022.08.001}, pmid = {36241544}, issn = {2341-2879}, mesh = {Child ; Humans ; RNA, Ribosomal, 16S/genetics/analysis ; Case-Control Studies ; *Mucocutaneous Lymph Node Syndrome ; Nasopharynx/chemistry/microbiology ; *Microbiota/genetics ; Corynebacterium/genetics ; }, abstract = {INTRODUCTION: The aetiology of Kawasaki disease (KD) remains unknown. Several studies have linked the human microbiome with some diseases. However, there are limited studies on the role of the respiratory microbiome in KD. The aim of our study was to make a more thorough analysis of the causes and processes that increase the susceptibility to KD.<br><br>METHODS: Case-control study comparing the respiratory microbiome of KD patients with that of healthy children. The V3-V4 region of the 16S rRNA bacterial gene and 16 respiratory viruses were analysed by real-time polimerase-chain reaction. We used the Ribosomal Database Project (RDP) version 11.5 (taxonomic assignment).<br><br>RESULTS: The initial sample included 11 cases and 11 controls matched for age, sex and seasonality. One of the cases was excluded to poor sample quality. The final analysis included 10 cases and 10 controls. In the case group, the analysis detected Haemophilus, Moraxella, Streptococcus and Corynebacterium species (27.62%, 19.71%, 25.28%, 11.86%, respectively). In the control group, it found Haemophilus, Streptococcus, Moraxella, and Dolosigranulum species (38.59%, 23.71%, 16.08, 8.93%, respectively). We found a higher relative abundance of Corynebacterium in patients with KD (11.86% vs. 1.55%; P&#x202f;=&#x202f;0.004).<br><br>CONCLUSIONS: To our knowledge, this is the first study that has found differences in the composition of the respiratory microbiome between patients with KD and healthy controls. The relative abundance of Corynebacterium spp. was greater in the KD group. This study shows differences in the microbiome between cases and controls, which suggests that the microbiome may play a role in facilitating the development of KD.}, }
@article {pmid36240246, year = {2022}, author = {Gauthier, NPG and Locher, K and MacDonald, C and Chorlton, SD and Charles, M and Manges, AR}, title = {Alterations in the nasopharyngeal microbiome associated with SARS-CoV-2 infection status and disease severity.}, journal = {PloS one}, volume = {17}, number = {10}, pages = {e0275815}, pmid = {36240246}, issn = {1932-6203}, mesh = {*COVID-19 ; Humans ; *Microbiota ; Nasopharynx ; Pandemics/prevention &amp; control ; RNA, Ribosomal, 16S/genetics ; SARS-CoV-2 ; Severity of Illness Index ; }, abstract = {OBJECTIVES: The COVID-19 pandemic and ensuing public health emergency has emphasized the need to study SARS-CoV-2 pathogenesis. The human microbiome has been shown to regulate the host immune system and may influence host susceptibility to viral infection, as well as disease severity. Several studies have assessed whether compositional alterations in the nasopharyngeal microbiota are associated with SARS-CoV-2 infection. However, the results of these studies were varied, and many did not account for disease severity. This study aims to examine whether compositional differences in the nasopharyngeal microbiota are associated with SARS-CoV-2 infection status and disease severity.<br><br>METHODS: We performed Nanopore full-length 16S rRNA sequencing on 194 nasopharyngeal swab specimens from hospitalized and community-dwelling SARS-CoV-2-infected and uninfected individuals. Sequence data analysis was performed using the BugSeq 16S analysis pipeline.<br><br>RESULTS: We found significant beta (PERMANOVA p < 0.05), but not alpha (Kruskal-Wallis p > 0.05) diversity differences in the nasopharyngeal microbiota among our study groups. We identified several differentially abundant taxa associated with SARS-CoV-2 infection status and disease severity using ALDEx2. Finally, we observed a trend towards higher abundance of Enterobacteriaceae in specimens from hospitalized SARS-CoV-2-infected patients.<br><br>CONCLUSIONS: This study identified several alterations in the nasopharyngeal microbiome associated with SARS-CoV-2 infection status and disease severity. Understanding the role of the microbiome in infection susceptibility and severity may open new avenues of research for disease prevention and treatment.}, }
@article {pmid36238714, year = {2022}, author = {Merrill, BD and Carter, MM and Olm, MR and Dahan, D and Tripathi, S and Spencer, SP and Yu, B and Jain, S and Neff, N and Jha, AR and Sonnenburg, ED and Sonnenburg, JL}, title = {Ultra-deep Sequencing of Hadza Hunter-Gatherers Recovers Vanishing Gut Microbes.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {36238714}, issn = {2692-8205}, support = {DP1 AT009892/AT/NCCIH NIH HHS/United States ; F32 DK128865/DK/NIDDK NIH HHS/United States ; R01 DK085025/DK/NIDDK NIH HHS/United States ; T32 AI007328/AI/NIAID NIH HHS/United States ; }, abstract = {The gut microbiome is a key modulator of immune and metabolic health. Human microbiome data is biased towards industrialized populations, providing limited understanding of the distinct and diverse non-industrialized microbiomes. Here, we performed ultra-deep metagenomic sequencing and strain cultivation on 351 fecal samples from the Hadza, hunter-gatherers in Tanzania, and comparative populations in Nepal and California. We recover 94,971 total genomes of bacteria, archaea, bacteriophages, and eukaryotes, 43% of which are absent from existing unified datasets. Analysis of in situ growth rates, genetic pN/pS signatures, high-resolution strain tracking, and 124 gut-resident species vanishing in industrialized populations reveals differentiating dynamics of the Hadza gut microbiome. Industrialized gut microbes are enriched in genes associated with oxidative stress, possibly a result of microbiome adaptation to inflammatory processes. This unparalleled view of the Hadza gut microbiome provides a valuable resource that expands our understanding of microbes capable of colonizing the human gut and clarifies the extensive perturbation brought on by the industrialized lifestyle.}, }
@article {pmid36232866, year = {2022}, author = {Uzelac, M and Li, Y and Chakladar, J and Li, WT and Ongkeko, WM}, title = {Archaea Microbiome Dysregulated Genes and Pathways as Molecular Targets for Lung Adenocarcinoma and Squamous Cell Carcinoma.}, journal = {International journal of molecular sciences}, volume = {23}, number = {19}, pages = {}, pmid = {36232866}, issn = {1422-0067}, mesh = {*Adenocarcinoma of Lung/pathology ; Archaea/genetics ; *Carcinoma, Non-Small-Cell Lung/genetics ; *Carcinoma, Squamous Cell/pathology ; Female ; Humans ; *Lung Neoplasms/pathology ; Male ; *Microbiota/genetics ; }, abstract = {The human microbiome is a vast collection of microbial species that exist throughout the human body and regulate various bodily functions and phenomena. Of the microbial species that exist in the human microbiome, those within the archaea domain have not been characterized to the extent of those in more common domains, despite their potential for unique metabolic interaction with host cells. Research has correlated tumoral presence of bacterial microbial species to the development and progression of lung cancer; however, the impacts and influences of archaea in the microbiome remain heavily unexplored. Within the United States lung cancer remains highly fatal, responsible for over 100,000 deaths every year with a 5-year survival rate of roughly 22.9%. This project attempts to investigate specific archaeal species' correlation to lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) incidence, patient staging, death rates across individuals of varying ages, races, genders, and smoking-statuses, and potential molecular targets associated with archaea microbiome. Archaeal species abundance was assessed across lung tissue samples of 527 LUAD patients, 479 LUSC patients, and 99 healthy individuals. Nine archaeal species were found to be of significantly altered abundance in cancerous samples as compared to normal counterparts, 6 of which are common to both LUAD and LUSC subgroups. Several of these species are of the taxonomic class Thermoprotei or the phylum Euryarchaeota, both known to contain metabolic processes distinct from most bacterial species. Host-microbe metabolic interactions may be responsible for the observed correlation of these species' abundance with cancer incidence. Significant microbes were correlated to patient gene expression to reveal genes of altered abundance with respect to high and low archaeal presence. With these genes, cellular oncogenic signaling pathways were analyzed for enrichment across cancer and normal samples. In comparing gene expression between LUAD and adjacent normal samples, 2 gene sets were found to be significantly enriched in cancers. In LUSC comparison, 6 sets were significantly enriched in cancer, and 34 were enriched in normals. Microbial counts across healthy and cancerous patients were then used to develop a machine-learning based predictive algorithm, capable of distinguishing lung cancer patients from healthy normal with 99% accuracy.}, }
@article {pmid36231000, year = {2022}, author = {Prakash, A and Nourianpour, M and Senok, A and Atiomo, W}, title = {Polycystic Ovary Syndrome and Endometrial Cancer: A Scoping Review of the Literature on Gut Microbiota.}, journal = {Cells}, volume = {11}, number = {19}, pages = {}, pmid = {36231000}, issn = {2073-4409}, mesh = {Dysbiosis/complications/microbiology ; *Endometrial Neoplasms ; Female ; *Gastrointestinal Microbiome/physiology ; Humans ; *Microbiota ; *Polycystic Ovary Syndrome ; }, abstract = {Gut dysbiosis has been associated with polycystic ovary syndrome (PCOS) and endometrial cancer (EC) but no studies have investigated whether gut dysbiosis may explain the increased endometrial cancer risk in polycystic ovary syndrome. The aim of this scoping review is to evaluate the extent and nature of published studies on the gut microbiota in polycystic ovary syndrome and endometrial cancer and attempt to find any similarities between the composition of the microbiota. We searched for publications ranging from the years 2016 to 2022, due to the completion date of the 'Human Microbiome Project' in 2016. We obtained 200 articles by inputting keywords such as 'gut microbiome', 'gut microbiota', 'gut dysbiosis', 'PCOS', and 'endometrial cancer' into search engines such as PubMed and Scopus. Of the 200 identified in our initial search, we included 25 articles in our final review after applying the exclusion and inclusion criteria. Although the literature is growing in this field, we did not identify enough published studies to investigate whether gut dysbiosis may explain the increased EC risk in PCOS. Within the studies identified, we were unable to identify any consistent patterns of the microbiome similarly present in studies on women with PCOS compared with women with EC. Although we found that the phylum Firmicutes was similarly decreased in women with PCOS and studies on women with EC, there was however significant variability within the studies identified making it highly likely that this may have arisen by chance. Further research pertaining to molecular and microbiological mechanisms in relation to the gut microbiome is needed to elucidate a greater understanding of its contribution to the pathophysiology of endometrial cancer in patients with polycystic ovarian syndrome.}, }
@article {pmid36220576, year = {2022}, author = {Campana, AM and Laue, HE and Shen, Y and Shrubsole, MJ and Baccarelli, AA}, title = {Assessing the role of the gut microbiome at the interface between environmental chemical exposures and human health: Current knowledge and challenges.}, journal = {Environmental pollution (Barking, Essex : 1987)}, volume = {315}, number = {}, pages = {120380}, pmid = {36220576}, issn = {1873-6424}, support = {P30 CA023108/CA/NCI NIH HHS/United States ; T32 CA134286/CA/NCI NIH HHS/United States ; }, mesh = {Humans ; *Gastrointestinal Microbiome ; Environmental Exposure ; *Microbiota ; *Environmental Pollutants/toxicity ; Hazardous Substances/toxicity ; }, abstract = {The explosion of microbiome research over the past decade has shed light on the various ways that external factors interact with the human microbiome to drive health and disease. Each individual is exposed to more than 300 environmental chemicals every day. Accumulating evidence indicates that the microbiome is involved in the early response to environmental toxicants and biologically mediates their adverse effects on human health. However, few review articles to date provided a comprehensive framework for research and translation of the role of the gut microbiome in environmental health science. This review summarizes current evidence on environmental compounds and their effect on the gut microbiome, discusses the involved compound metabolic pathways, and covers environmental pollution-induced gut microbiota disorders and their long-term outcomes on host health. We conclude that the gut microbiota may crucially mediate and modify the disease-causing effects of environmental chemicals. Consequently, gut microbiota needs to be further studied to assess the complete toxicity of environmental exposures. Future research in this field is required to delineate the key interactions between intestinal microbiota and environmental pollutants and further to elucidate the long-term human health effects.}, }
@article {pmid36219547, year = {2022}, author = {Zubeldia-Varela, E and Barker-Tejeda, TC and Obeso, D and Villaseñor, A and Barber, D and Pérez-Gordo, M}, title = {Microbiome and Allergy: New Insights and Perspectives.}, journal = {Journal of investigational allergology &amp; clinical immunology}, volume = {32}, number = {5}, pages = {327-344}, doi = {10.18176/jiaci.0852}, pmid = {36219547}, issn = {1018-9068}, mesh = {Allergens ; Dysbiosis ; *Food Hypersensitivity ; *Gastrointestinal Microbiome ; Humans ; *Microbiota ; }, abstract = {The role of the microbiome in the molecular mechanisms underlying allergy has become highly relevant in recent years. Studies are increasingly suggesting that altered composition of the microbiota, or dysbiosis, may result in local and systemic alteration of the immune response to specific allergens. In this regard, a link has been established between lung microbiota and respiratory allergy, between skin microbiota and atopic dermatitis, and between gut microbiota and food allergy. The composition of the human microbiota is dynamic and depends on host-associated factors such as diet, diseases, and lifestyle. Omics are the techniques of choice for the analysis and understanding of the microbiota. Microbiota analysis techniques have advanced considerably in recent decades, and the need for multiple approaches to explore and comprehend multifactorial diseases, including allergy, has increased. Thus, more and more studies are proposing mechanisms for intervention in the microbiota. In this review, we present the latest advances with respect to the human microbiota in the literature, focusing on the intestinal, cutaneous, and respiratory microbiota. We discuss the relationship between the microbiome and the immune system, with emphasis on allergic diseases. Finally, we discuss the main technologies for the study of the microbiome and interventions targeting the microbiota for prevention of allergy.}, }
@article {pmid36215042, year = {2023}, author = {Wishart, DS and Oler, E and Peters, H and Guo, A and Girod, S and Han, S and Saha, S and Lui, VW and LeVatte, M and Gautam, V and Kaddurah-Daouk, R and Karu, N}, title = {MiMeDB: the Human Microbial Metabolome Database.}, journal = {Nucleic acids research}, volume = {51}, number = {D1}, pages = {D611-D620}, pmid = {36215042}, issn = {1362-4962}, support = {U19 AG063744/AG/NIA NIH HHS/United States ; }, mesh = {Humans ; *Metabolomics ; *Proteomics ; Metabolome/genetics ; Databases, Factual ; Data Management ; }, abstract = {The Human Microbial Metabolome Database (MiMeDB) (https://mimedb.org) is a comprehensive, multi-omic, microbiome resource that connects: (i) microbes to microbial genomes; (ii) microbial genomes to microbial metabolites; (iii) microbial metabolites to the human exposome and (iv) all of these 'omes' to human health. MiMeDB was established to consolidate the growing body of data connecting the human microbiome and the chemicals it produces to both health and disease. MiMeDB contains detailed taxonomic, microbiological and body-site location data on most known human microbes (bacteria and fungi). This microbial data is linked to extensive genomic and proteomic sequence data that is closely coupled to colourful interactive chromosomal maps. The database also houses detailed information about all the known metabolites generated by these microbes, their structural, chemical and spectral properties, the reactions and enzymes responsible for these metabolites and the primary exposome sources (food, drug, cosmetic, pollutant, etc.) that ultimately lead to the observed microbial metabolites in humans. Additional, extensively referenced data about the known or presumptive health effects, measured biosample concentrations and human protein targets for these compounds is provided. All of this information is housed in richly annotated, highly interactive, visually pleasing database that has been designed to be easy to search, easy to browse and easy to navigate. Currently MiMeDB contains data on 626 health effects or bioactivities, 1904 microbes, 3112 references, 22 054 reactions, 24 254 metabolites or exposure chemicals, 648 861 MS and NMR spectra, 6.4 million genes and 7.6 billion DNA bases. We believe that MiMeDB represents the kind of integrated, multi-omic or systems biology database that is needed to enable comprehensive multi-omic integration.}, }
@article {pmid36209213, year = {2022}, author = {Wang, C and Zhang, L and Jiang, X and Ma, W and Geng, H and Wang, X and Li, M}, title = {Toward efficient and high-fidelity metagenomic data from sub-nanogram DNA: evaluation of library preparation and decontamination methods.}, journal = {BMC biology}, volume = {20}, number = {1}, pages = {225}, pmid = {36209213}, issn = {1741-7007}, mesh = {DNA/genetics ; *Decontamination ; Endonucleases/genetics ; Gene Library ; High-Throughput Nucleotide Sequencing/methods ; Humans ; *Metagenomics/methods ; Reproducibility of Results ; Sequence Analysis, DNA/methods ; }, abstract = {BACKGROUND: Shotgun metagenomic sequencing has greatly expanded the understanding of microbial communities in various biological niches. However, it is still challenging to efficiently convert sub-nanogram DNA to high-quality metagenomic libraries and obtain high-fidelity data, hindering the exploration of niches with low microbial biomass.<br><br>RESULTS: To cope with this challenge comprehensively, we evaluated the performance of various library preparation methods on 0.5&#xa0;pg-5&#xa0;ng synthetic microbial community DNA, characterized contaminants, and further applied different in silico decontamination methods. First, we discovered that whole genome amplification prior to library construction led to worse outcomes than preparing libraries directly. Among different non-WGA-based library preparation methods, we found the endonuclease-based method being generally good for different amounts of template and the tagmentation-based method showing specific advantages with 0.5&#xa0;pg template, based on evaluation metrics including fidelity, proportion of designated reads, and reproducibility. The load of contaminating DNA introduced by library preparation varied from 0.01 to 15.59&#xa0;pg for different kits and accounted for 0.05 to 45.97% of total reads. A considerable fraction of the contaminating reads were mapped to human commensal and pathogenic microbes, thus potentially leading to erroneous conclusions in human microbiome studies. Furthermore, the best performing in silico decontamination method in our evaluation, Decontam-either, was capable of recovering the real microbial community from libraries where contaminants accounted for less than 10% of total reads, but not from libraries with heavy and highly varied contaminants.<br><br>CONCLUSIONS: This study demonstrates that high-quality metagenomic data can be obtained from samples with sub-nanogram microbial DNA by combining appropriate library preparation and in silico decontamination methods and provides a general reference for method selection for samples with varying microbial biomass.}, }
@article {pmid36207756, year = {2022}, author = {Park, HM and Park, Y and Berani, U and Bang, E and Vankerschaver, J and Van Messem, A and De Neve, W and Shim, H}, title = {In silico optimization of RNA-protein interactions for CRISPR-Cas13-based antimicrobials.}, journal = {Biology direct}, volume = {17}, number = {1}, pages = {27}, pmid = {36207756}, issn = {1745-6150}, mesh = {Anti-Bacterial Agents ; Bacteria/genetics ; *CRISPR-Cas Systems ; Humans ; *RNA, Bacterial ; Ribonucleases/genetics/metabolism ; }, abstract = {RNA-protein interactions are crucial for diverse biological processes. In prokaryotes, RNA-protein interactions enable adaptive immunity through CRISPR-Cas systems. These defence systems utilize CRISPR RNA (crRNA) templates acquired from past infections to destroy foreign genetic elements through crRNA-mediated nuclease activities of Cas proteins. Thanks to the programmability and specificity of CRISPR-Cas systems, CRISPR-based antimicrobials have the potential to be repurposed as new types of antibiotics. Unlike traditional antibiotics, these CRISPR-based antimicrobials can be designed to target specific bacteria and minimize detrimental effects on the human microbiome during antibacterial therapy. In this study, we explore the potential of CRISPR-based antimicrobials by optimizing the RNA-protein interactions of crRNAs and Cas13 proteins. CRISPR-Cas13 systems are unique as they degrade specific foreign RNAs using the crRNA template, which leads to non-specific RNase activities and cell cycle arrest. We show that a high proportion of the Cas13 systems have no colocalized CRISPR arrays, and the lack of direct association between crRNAs and Cas proteins may result in suboptimal RNA-protein interactions in the current tools. Here, we investigate the RNA-protein interactions of the Cas13-based systems by curating the validation dataset of Cas13 protein and CRISPR repeat pairs that are experimentally validated to interact, and the candidate dataset of CRISPR repeats that reside on the same genome as the currently known Cas13 proteins. To find optimal CRISPR-Cas13 interactions, we first validate the 3-D structure prediction of crRNAs based on their experimental structures. Next, we test a number of RNA-protein interaction programs to optimize the in silico docking of crRNAs with the Cas13 proteins. From this optimized pipeline, we find a number of candidate crRNAs that have comparable or better in silico docking with the Cas13 proteins of the current tools. This study fully automatizes the in silico optimization of RNA-protein interactions as an efficient preliminary step for designing effective CRISPR-Cas13-based antimicrobials.}, }
@article {pmid36202806, year = {2022}, author = {Shetty, SA and Kuipers, B and Atashgahi, S and Aalvink, S and Smidt, H and de Vos, WM}, title = {Author Correction: Inter-species metabolic interactions in an in-vitro minimal human gut microbiome of core bacteria.}, journal = {NPJ biofilms and microbiomes}, volume = {8}, number = {1}, pages = {76}, doi = {10.1038/s41522-022-00339-3}, pmid = {36202806}, issn = {2055-5008}, }
@article {pmid36198908, year = {2023}, author = {VanEvery, H and Franzosa, EA and Nguyen, LH and Huttenhower, C}, title = {Microbiome epidemiology and association studies in human health.}, journal = {Nature reviews. Genetics}, volume = {24}, number = {2}, pages = {109-124}, pmid = {36198908}, issn = {1471-0064}, support = {T32 DK007703/DK/NIDDK NIH HHS/United States ; K23 DK125838/DK/NIDDK NIH HHS/United States ; R24 DK110499/DK/NIDDK NIH HHS/United States ; }, mesh = {Humans ; *Genome-Wide Association Study ; *Microbiota/genetics ; High-Throughput Nucleotide Sequencing ; }, abstract = {Studies of the human microbiome share both technical and conceptual similarities with genome-wide association studies and genetic epidemiology. However, the microbiome has many features that differ from genomes, such as its temporal and spatial variability, highly distinct genetic architecture and person-to-person variation. Moreover, there are various potential mechanisms by which distinct aspects of the human microbiome can relate to health outcomes. Recent advances, including next-generation sequencing and the proliferation of multi-omic data types, have enabled the exploration of the mechanisms that connect microbial communities to human health. Here, we review the ways in which features of the microbiome at various body sites can influence health outcomes, and we describe emerging opportunities and future directions for advanced microbiome epidemiology.}, }
@article {pmid36189340, year = {2022}, author = {Poroyko, V and Manuel, ER and Ilina, E}, title = {Editorial: The human microbiome: A new frontier in personalized cancer therapy.}, journal = {Frontiers in cellular and infection microbiology}, volume = {12}, number = {}, pages = {1028120}, doi = {10.3389/fcimb.2022.1028120}, pmid = {36189340}, issn = {2235-2988}, mesh = {*Gastrointestinal Microbiome ; Humans ; *Microbiota ; *Neoplasms/therapy ; }, }
@article {pmid36189145, year = {2022}, author = {Kasperkiewicz, K and Świerzko, AS and Michalski, M and Eppa, &#x141; and Skurnik, M and Żuber, Z and Cedzyński, M}, title = {Antibodies Recognizing Yersinia enterocolitica Lipopolysaccharides of Various Chemotypes in Synovial Fluids From Patients With Juvenile Idiopathic Arthritis.}, journal = {Journal of immunology research}, volume = {2022}, number = {}, pages = {9627934}, pmid = {36189145}, issn = {2314-7156}, mesh = {Animals ; Antibodies/metabolism ; Antigens, Bacterial ; *Arthritis, Juvenile ; Lectins/metabolism ; Lipid A ; Lipopolysaccharides ; Mice ; O Antigens ; Synovial Fluid ; *Yersinia enterocolitica ; }, abstract = {Yersinia enterocolitica O:3 (YeO3) is considered to be associated with reactive arthritis (ReA), and its lipopolysaccharide (LPS) has been detected in synovial fluids from patients. Interestingly, YeO3 wild-type LPS was processed by host cells, resulting in truncated LPS molecules presenting the core region. Previously, we reported the immunogenicity but not adjuvanticity of YeO3 LPSs of wild (S) type, Ra, Rd, or Re chemotypes in mice. Here, we demonstrate the presence of YeO3 LPS chemotype-specific antibodies in all analyzed synovial fluids (SF) from patients with juvenile idiopathic arthritis (JIA). Interestingly, the high titer of antibodies specific for the Kdo-lipid A region was found in most tested SF. In contrast, only a few were positive for antibodies recognizing O-specific polysaccharides. Western blot analysis revealed the presence of antibodies reacting with fast-migrating LPS fractions and enterobacterial common antigen (ECA) in synovial fluid samples. Our data also suggest the importance of LPS-associated ECA for the antigenicity of endotoxin. Furthermore, we confirmed in vitro that Yersinia LPS processing leads to the exposure of its core region and enhanced potency of complement lectin pathway activation.}, }
@article {pmid36179671, year = {2022}, author = {Dohlman, AB and Klug, J and Mesko, M and Gao, IH and Lipkin, SM and Shen, X and Iliev, ID}, title = {A pan-cancer mycobiome analysis reveals fungal involvement in gastrointestinal and lung tumors.}, journal = {Cell}, volume = {185}, number = {20}, pages = {3807-3822.e12}, pmid = {36179671}, issn = {1097-4172}, support = {R35 GM122465/GM/NIGMS NIH HHS/United States ; R01 DK121977/DK/NIDDK NIH HHS/United States ; P30 CA008748/CA/NCI NIH HHS/United States ; P30 CA014236/CA/NCI NIH HHS/United States ; R01 AI163007/AI/NIAID NIH HHS/United States ; R01 DK113136/DK/NIDDK NIH HHS/United States ; UL1 TR002384/TR/NCATS NIH HHS/United States ; R01 DK119795/DK/NIDDK NIH HHS/United States ; U01 CA214300/CA/NCI NIH HHS/United States ; }, mesh = {Biomarkers ; Candida/genetics ; DNA, Fungal ; Fungi/genetics ; Humans ; *Lung Neoplasms ; *Mycobiome ; }, abstract = {Fungal microorganisms (mycobiota) comprise a small but immunoreactive component of the human microbiome, yet little is known about their role in human cancers. Pan-cancer analysis of multiple body sites revealed tumor-associated mycobiomes at up to 1 fungal cell per 10[4] tumor cells. In lung cancer, Blastomyces was associated with tumor tissues. In stomach cancers, high rates of Candida were linked to the expression of pro-inflammatory immune pathways, while in colon cancers Candida was predictive of metastatic disease and attenuated cellular adhesions. Across multiple GI sites, several Candida species were enriched in tumor samples and tumor-associated Candida DNA was predictive of decreased survival. The presence of Candida in human GI tumors was confirmed by external ITS sequencing of tumor samples and by culture-dependent analysis in an independent cohort. These data implicate the mycobiota in the pathogenesis of GI cancers and suggest that tumor-associated fungal DNA may serve as diagnostic or prognostic biomarkers.}, }
@article {pmid36175995, year = {2022}, author = {Carpén, N and Brodin, P and de Vos, WM and Salonen, A and Kolho, KL and Andersson, S and Helve, O}, title = {Transplantation of maternal intestinal flora to the newborn after elective cesarean section (SECFLOR): study protocol for a double blinded randomized controlled trial.}, journal = {BMC pediatrics}, volume = {22}, number = {1}, pages = {565}, pmid = {36175995}, issn = {1471-2431}, mesh = {Cesarean Section/adverse effects ; Child, Preschool ; Feces ; Female ; *Gastrointestinal Microbiome ; Humans ; Infant ; Infant, Newborn ; Intestines ; Milk, Human ; Pregnancy ; Randomized Controlled Trials as Topic ; }, abstract = {BACKGROUND: A complication of elective cesarean section (CS) delivery is its interference with the normal intestinal colonization of the infant, affecting the immune and metabolic signaling in early life- a process that has been associated with long-term morbidity, such as allergy and diabetes. We evaluate, in CS-delivered infants, whether the normal intestinal microbiome and its early life development can be restored by immediate postnatal transfer of maternal fecal microbiota (FMT) to the newborn, and how this procedure influences the maturation of the immune system.<br><br>METHODS: Sixty healthy mothers with planned elective CS are recruited and screened thoroughly for infections. A maternal fecal sample is taken prior to delivery and processed according to a transplantation protocol. After double blinded randomization, half of the newborns will receive a diluted aliquot of their own mother's stool orally administered in breast milk during the first feeding while the other half will be similarly treated with a placebo. The infants are clinically followed, and fecal samples are gathered weekly until the age of 4&#xa0;weeks, then at the ages of 8&#xa0;weeks, 3, 6, 12 and 24&#xa0;months. The parents fill in questionnaires until the age of 24&#xa0;months. Blood samples are taken at the age of 2-3&#xa0;days and 3, 6, 12 and 24&#xa0;months to assess development of major immune cell populations and plasma proteins throughout the first years of life.<br><br>DISCUSSION: This is the first study to assess long-time effects on the intestinal microbiome and the development of immune system of a maternal fecal transplant given to term infants born by CS.<br><br>TRIAL REGISTRATION: ClinicalTrials.gov NCT04173208 , registration date 21.11.2019.}, }
@article {pmid36175428, year = {2022}, author = {Peters, SL and Borges, AL and Giannone, RJ and Morowitz, MJ and Banfield, JF and Hettich, RL}, title = {Experimental validation that human microbiome phages use alternative genetic coding.}, journal = {Nature communications}, volume = {13}, number = {1}, pages = {5710}, pmid = {36175428}, issn = {2041-1723}, support = {R01 GM103600/GM/NIGMS NIH HHS/United States ; }, mesh = {*Bacteriophages/genetics ; Chromatography, Liquid ; Codon, Terminator ; Glutamine ; Humans ; *Microbiota/genetics ; Proteomics ; Tandem Mass Spectrometry ; }, abstract = {Previous bioinformatic analyses of metagenomic data have indicated that bacteriophages can use genetic codes different from those of their host bacteria. In particular, reassignment of stop codon TAG to glutamine (a variation known as 'genetic code 15') has been predicted. Here, we use LC-MS/MS-based metaproteomics of human fecal samples to provide experimental evidence of the use of genetic code 15 in two crAss-like phages. Furthermore, the proteomic data from several phage structural proteins supports the reassignment of the TAG stop codon to glutamine late in the phage infection cycle. Thus, our work experimentally validates the expression of genetic code 15 in human microbiome phages.}, }
@article {pmid36174236, year = {2022}, author = {Jokela, R and Korpela, K and Jian, C and Dikareva, E and Nikkonen, A and Saisto, T and Skogberg, K and de Vos, WM and Kolho, KL and Salonen, A}, title = {Quantitative insights into effects of intrapartum antibiotics and birth mode on infant gut microbiota in relation to well-being during the first year of life.}, journal = {Gut microbes}, volume = {14}, number = {1}, pages = {2095775}, pmid = {36174236}, issn = {1949-0984}, mesh = {Anti-Bacterial Agents/pharmacology ; Cephalosporins ; Cesarean Section ; Female ; *Gastrointestinal Microbiome ; Humans ; Infant ; Monobactams ; Penicillins ; Pregnancy ; RNA, Ribosomal, 16S/genetics ; }, abstract = {Birth mode and maternal intrapartum (IP) antibiotics affect infants' gut microbiota development, but their relative contribution to absolute bacterial abundances and infant health has not been studied. We compared the effects of Cesarean section (CS) delivery and IP antibiotics on infant gut microbiota development and well-being over the first year. We focused on 92 healthy infants born between gestational weeks 37-42 vaginally without antibiotics (N = 26), with IP penicillin (N = 13) or cephalosporin (N = 7) or by CS with IP cephalosporin (N = 33) or other antibiotics (N = 13). Composition and temporal development analysis of the gut microbiota concentrated on 5 time points during the first year of life using 16S rRNA gene amplicon sequencing, integrated with qPCR to obtain absolute abundance estimates. A mediation analysis was carried out to identify taxa linked to gastrointestinal function and discomfort (crying, defecation frequency, and signs of gastrointestinal symptoms), and birth interventions. Based on absolute abundance estimates, the depletion of Bacteroides spp. was found specifically in CS birth, while decreased bifidobacteria and increased Bacilli were common in CS birth and exposure to IP antibiotics in vaginal delivery. The abundances of numerous taxa differed between the birth modes among cephalosporin-exposed infants. Penicillin had a milder impact on the infant gut microbiota than cephalosporin. CS birth and maternal IP antibiotics had both specific and overlapping effects on infants' gut microbiota development. The resulting deviations in the gut microbiota are associated with increased defecation rate, flatulence, perceived stomach pain, and intensity of crying in infancy.}, }
@article {pmid36172175, year = {2022}, author = {Mousa, WK}, title = {The microbiome-product colibactin hits unique cellular targets mediating host-microbe interaction.}, journal = {Frontiers in pharmacology}, volume = {13}, number = {}, pages = {958012}, pmid = {36172175}, issn = {1663-9812}, abstract = {The human microbiota produces molecules that are evolved to interact with the diverse cellular machinery of both the host and microbes, mediating health and diseases. One of the most puzzling microbiome molecules is colibactin, a genotoxin encoded in some commensal and extraintestinal microbes and is implicated in initiating colorectal cancer. The colibactin cluster was discovered more than 15 years ago, and most of the research studies have been focused on revealing the biosynthesis and precise structure of the cryptic encoded molecule(s) and the mechanism of carcinogenesis. In 2022, the Balskus group revealed that colibactin not only hits targets in the eukaryotic cell machinery but also in the prokaryotic cell. To that end, colibactin crosslinks the DNA resulting in activation of the SOS signaling pathway, leading to prophage induction from bacterial lysogens and modulation of virulence genes in pathogenic species. These unique activities of colibactin highlight its ecological role in shaping gut microbial communities and further consequences that impact human health. This review dives in-depth into the molecular mechanisms underpinning colibactin cellular targets in eukaryotic and prokaryotic cells, aiming to understand the fine details of the role of secreted microbiome chemistry in mediating host-microbe and microbe-microbe interactions. This understanding translates into a better realization of microbiome potential and how this could be advanced to future microbiome-based therapeutics or diagnostic biomarkers.}, }
@article {pmid36171273, year = {2022}, author = {Oduaran, OH and Bhatt, AS}, title = {Equitable partnerships and the path to inclusive, innovative and impactful human microbiome research.}, journal = {Nature reviews. Gastroenterology &amp; hepatology}, volume = {19}, number = {11}, pages = {683-684}, pmid = {36171273}, issn = {1759-5053}, support = {U54 HG006938/HG/NHGRI NIH HHS/United States ; }, mesh = {Humans ; *Microbiota ; }, }
@article {pmid36171082, year = {2023}, author = {Jalanka, J and Gunn, D and Singh, G and Krishnasamy, S and Lingaya, M and Crispie, F and Finnegan, L and Cotter, P and James, L and Nowak, A and Major, G and Spiller, RC}, title = {Postinfective bowel dysfunction following Campylobacter enteritis is characterised by reduced microbiota diversity and impaired microbiota recovery.}, journal = {Gut}, volume = {72}, number = {3}, pages = {451-459}, pmid = {36171082}, issn = {1468-3288}, support = {/DH_/Department of Health/United Kingdom ; }, mesh = {Humans ; Cohort Studies ; RNA, Ribosomal, 16S/genetics ; *Gastroenteritis ; *Microbiota ; *Campylobacter Infections ; *Campylobacter ; *Enteritis ; *Irritable Bowel Syndrome ; }, abstract = {OBJECTIVES: Persistent bowel dysfunction following gastroenteritis (postinfectious (PI)-BD) is well recognised, but the associated changes in microbiota remain unclear. Our aim was to define these changes after gastroenteritis caused by a single organism, Campylobacter jejuni, examining the dynamic changes in the microbiota and the impact of antibiotics.<br><br>DESIGN: A single-centre cohort study of 155 patients infected with Campylobacter jejuni. Features of the initial illness as well as current bowel symptoms and the intestinal microbiota composition were recorded soon after infection (visit 1, <40&#x2009;days) as well as 40-60&#x2009;days and >80&#x2009;days later (visits 2 and 3). Microbiota were assessed using 16S rRNA sequencing.<br><br>RESULTS: PI-BD was found in 22 of the 99 patients who completed the trial. The cases reported significantly looser stools, with more somatic and gastrointestinal symptoms. Microbiota were assessed in 22 cases who had significantly lower diversity and altered microbiota composition compared with the 44 age-matched and sex-matched controls. Moreover 60 days after infection, cases showed a significantly lower abundance of 23 taxa including phylum Firmicutes, particularly in the order Clostridiales and the family Ruminoccocaceae, increased Proteobacteria abundance and increased levels of Fusobacteria and Gammaproteobacteria. The microbiota changes were linked with diet; higher fibre consumption being associated with lower levels of Gammaproteobacteria.<br><br>CONCLUSION: The microbiota of PI-BD patients appeared more disturbed by the initial infection compared with the microbiota of those who recovered. The prebiotic effect of high fibre diets may inhibit some of the disturbances seen in PI-BD.<br><br>TRIAL REGISTRATION NUMBER: NCT02040922.}, }
@article {pmid36168359, year = {2022}, author = {Sheldon, JM and Alonso, N}, title = {The Therapeutic Benefits of Single and Multi-Strain Probiotics on Mean Daily Crying Time and Key Inflammatory Markers in Infantile Colic.}, journal = {Cureus}, volume = {14}, number = {8}, pages = {e28363}, pmid = {36168359}, issn = {2168-8184}, abstract = {Infantile colic is a functional gastrointestinal disorder in which a healthy infant displays paroxysms of intense crying or fussiness. Although this condition is self-limited, it causes significant distress for parents and may be linked to long-term health concerns for children. The microbiome of infants with colic has been correlated with increased dysbiosis or imbalance of commensal bacteria. This dysbiosis may ultimately lead to changes in infants' immunological profiles, favoring markers linked to inflammation, including specific cytokines, calprotectin, and genetic markers. Therapeutic regimens such as probiotics may be helpful in modifying the gut microbial composition, thereby influencing the presence of inflammatory markers and potentially reducing colic symptoms in infants. This review provides a summary of the findings from 10 randomized, placebo-controlled, double-blinded studies conducted in the past five years with the aim of examining the potential therapeutic benefits of probiotics in infantile colic. The articles were selected through PubMed and Google Scholar using the keywords infantile colic, microbiome, probiotics, cytokines, dysbiosis, inflammatory markers, and lactobacilli. We summarize the results of these studies to explore the potential anti-inflammatory therapeutic benefits of single and multi-strain probiotic formulations on daily crying time and key inflammatory markers in infants with colic. The research largely shows the beneficial role of probiotics, largely of the lactobacillus genus, in the reduction of colic symptoms and the reduction of key inflammatory markers. However, some studies demonstrated an insignificant effect of certain probiotic strains in symptom management. Further research is necessary to better understand the anti-inflammatory properties of probiotics and determine the role this could have on the manifestation of colic in infants.}, }
@article {pmid36163368, year = {2022}, author = {Yang, Q and Van Haute, M and Korth, N and Sattler, SE and Toy, J and Rose, DJ and Schnable, JC and Benson, AK}, title = {Genetic analysis of seed traits in Sorghum bicolor that affect the human gut microbiome.}, journal = {Nature communications}, volume = {13}, number = {1}, pages = {5641}, pmid = {36163368}, issn = {2041-1723}, mesh = {Crops, Agricultural ; Edible Grain/genetics ; *Gastrointestinal Microbiome/genetics ; Humans ; Polyphenols ; *Proanthocyanidins ; Seeds/genetics ; *Sorghum/genetics ; }, abstract = {Prebiotic fibers, polyphenols and other molecular components of food crops significantly affect the composition and function of the human gut microbiome and human health. The abundance of these, frequently uncharacterized, microbiome-active components vary within individual crop species. Here, we employ high throughput in vitro fermentations of pre-digested grain using a human microbiome to identify segregating genetic loci in a food crop, sorghum, that alter the composition and function of human gut microbes. Evaluating grain produced by 294 sorghum recombinant inbreds identifies 10 loci in the sorghum genome associated with variation in the abundance of microbial taxa and/or microbial metabolites. Two loci co-localize with sorghum genes regulating the biosynthesis of condensed tannins. We validate that condensed tannins stimulate the growth of microbes associated with these two loci. Our work illustrates the potential for genetic analysis to systematically discover and characterize molecular components of food crops that influence the human gut microbiome.}, }
@article {pmid36160151, year = {2022}, author = {Aboul Naga, SH and Hassan, LM and El Zanaty, RT and Refaat, M and Amin, RH and Ragab, G and Soliman, MM}, title = {Behçet uveitis: Current practice and future perspectives.}, journal = {Frontiers in medicine}, volume = {9}, number = {}, pages = {968345}, pmid = {36160151}, issn = {2296-858X}, abstract = {Described as early as Hippocrates in his "Third Book of Endemic Diseases," Behçet's Disease (BD), also known as "The Silk Road Disease" following its initial demographics, consists of a triad of recurrent oro-genital ulcers and associated uveitis. Current demographics and rising percentages of patients seen far beyond the Silk Road in Ocular Inflammatory Disease and Uveitis Clinics list BD uveitis as one of the frontliners of non-infectious autoinflammatory eye diseases. Clinical features of BD and juvenile-onset BD are detailed alongside various approaches in classification and suggested algorithms for diagnosis that are outlined in this review. With the ongoing Human Microbiome Project and studies such as the MAMBA study, the role of the human microbiome in BD is highlighted in the pathophysiology of BD to include the current research and literature perspective. Furthermore, with the advancement of recent diagnostic and investigative techniques, especially in the field of Optical Coherence Tomography (OCT), disease-related characteristics are updated to encompass SD, EDI and OCT-angiography characteristics of BD. Having entered the era of biologic therapy, the role of various specific cytokine-blocking biologic drugs, such as TNF-α inhibitors (e.g., adalimumab, infliximab), interferon α-2a inhibitors, IL-6 and IL-1 inhibitors are presented and contrasted alongside the conventional immunosuppressant drugs and the classic old gold standard: corticosteroids (systemic or local). Finally, with the ongoing SARS-CoV-2 pandemic, it was not possible to conclude the review without reviewing the latest evidence-based literature reporting BD morbidity in this era, the observed pattern and treatment recommendations as well as those related to reported post-vaccine complications and emergence of BD.}, }
@article {pmid36157871, year = {2022}, author = {Maslennikov, R and Efremova, I and Ivashkin, V and Zharkova, M and Poluektova, E and Shirokova, E and Ivashkin, K}, title = {Effect of probiotics on hemodynamic changes and complications associated with cirrhosis: A pilot randomized controlled trial.}, journal = {World journal of hepatology}, volume = {14}, number = {8}, pages = {1667-1677}, pmid = {36157871}, issn = {1948-5182}, abstract = {BACKGROUND: Bacterial translocation exacerbates the hyperdynamic circulation observed in cirrhosis and contributes to a more severe disease course. Probiotics may reduce bacterial translocation and may therefore be useful to redress the circulatory imbalance.<br><br>AIM: To investigate the effect of probiotics on hemodynamic parameters, systemic inflammation, and complications of cirrhosis in this randomized placebo-controlled trial.<br><br>METHODS: This single-blind randomized placebo-controlled study included 40 patients with Child-Pugh class B and C cirrhosis; 24 patients received probiotics (Saccharomyces boulardii) for 3 mo, and 16 patients received a placebo over the same period. Liver function and the systemic hemodynamic status were evaluated pre- and post-intervention. Echocardiography and simultaneous blood pressure and heart rate monitoring were performed to evaluate systemic hemodynamic indicators. Cardiac output and systemic vascular resistance were calculated.<br><br>RESULTS: Following a 3-mo course of probiotics in comparison to the control group, we observed amelioration of hyperdynamic circulation [a decrease in cardiac output (P = 0.026) and an increase in systemic vascular resistance (P = 0.026)] and systemic inflammation [a decrease in serum C-reactive protein levels (P = 0.044)], with improved liver function [an increase in serum albumin (P = 0.001) and a decrease in the value of Child-Pugh score (P = 0.001)] as well as a reduction in the severity of ascites (P = 0.022), hepatic encephalopathy (P = 0.048), and cholestasis [a decrease in serum alkaline phosphatase (P = 0.016) and serum gamma-glutamyl transpeptidase (P = 0.039) activity] and an increase in platelet counts (P < 0.001) and serum sodium level (P = 0.048).<br><br>CONCLUSION: Probiotic administration was associated with amelioration of hyperdynamic circulation and the associated complications of cirrhosis.}, }
@article {pmid36155349, year = {2022}, author = {Kumari, P and Prakash, P and Yadav, S and Saran, V}, title = {Microbiome analysis: An emerging forensic investigative tool.}, journal = {Forensic science international}, volume = {340}, number = {}, pages = {111462}, doi = {10.1016/j.forsciint.2022.111462}, pmid = {36155349}, issn = {1872-6283}, mesh = {Animals ; Female ; Forensic Medicine/methods ; Humans ; *Microbiota ; Narcotics ; Saliva ; Soil ; }, abstract = {Microbial diversity's potential has been investigated in medical and therapeutic studies throughout the last few decades. However, its usage in forensics is increasing due to its effectiveness in circumstances when traditional approaches fail to provide a decisive opinion or are insufficient in forming a concrete opinion. The application of human microbiome may serve in detecting the type of stains of saliva and vaginal fluid, as well as in attributing the stains to the individual. Similarly, the microbiome makeup of a soil sample may be utilised to establish geographic origin or to associate humans, animals, or things with a specific area, additionally microorganisms influence the decay process which may be used in depicting the Time Since death. Further in detecting the traces of the amount and concentration of alcohol, narcotics, and other forensically relevant compounds in human body or visceral tissues as they also affect the microbial community within human body. Beside these, there is much more scope of microbiomes to be explored in terms of forensic investigation, this review focuses on multidimensional approaches to human microbiomes from a forensic standpoint, implying the potential of microbiomes as an emerging tool for forensic investigations such as individual variability via skin microbiomes, reconstructing crime scene, and linking evidence to individual.}, }
@article {pmid36154442, year = {2022}, author = {Saha, UB and Saroj, SD}, title = {Lactic acid bacteria: prominent player in the fight against human pathogens.}, journal = {Expert review of anti-infective therapy}, volume = {20}, number = {11}, pages = {1435-1453}, doi = {10.1080/14787210.2022.2128765}, pmid = {36154442}, issn = {1744-8336}, mesh = {Humans ; *Lactobacillales ; Lactobacillus ; *Bacterial Infections/drug therapy/microbiology ; Bacteria ; *Microbiota ; *Probiotics/therapeutic use ; }, abstract = {INTRODUCTION: The human microbiome is a unique repository of diverse bacteria. Over 1000 microbial species reside in the human gut, which predominantly influences the host's internal environment and plays a significant role in host health. Lactic acid bacteria have long been employed for multiple purposes, ranging from food to medicines. Lactobacilli, which are often used in commercial food fermentation, have improved to the point that they might be helpful in medical applications.<br><br>AREAS COVERED: This review summarises various clinical and experimental evidence on efficacy of lactobacilli in treating a wide range of infections. Both laboratory based and clinical studies have been discussed.<br><br>EXPERT OPINION: Lactobacilli are widely accepted as safe biological treatments and host immune modulators (GRAS- Generally regarded as safe) by the US Food and Drug Administration and Qualified Presumption of Safety. Understanding the molecular mechanisms of lactobacilli in the treatment and pathogenicity of bacterial infections can help with the prediction and development of innovative therapeutics aimed at pathogens which have gained resistance to antimicrobials. To formulate effective lactobacilli based therapy significant research on the effectiveness of different lactobacilli strains and its association with demographic distribution is required. Also, the side effects of such therapy needs to be evaluated.}, }
@article {pmid36153116, year = {2022}, author = {White, MG and Wargo, JA}, title = {The Microbiome in Gastrointestinal Cancers.}, journal = {Gastroenterology clinics of North America}, volume = {51}, number = {3}, pages = {667-680}, doi = {10.1016/j.gtc.2022.06.007}, pmid = {36153116}, issn = {1558-1942}, support = {P30 CA016672/CA/NCI NIH HHS/United States ; R01 CA219896/CA/NCI NIH HHS/United States ; }, mesh = {*Gastrointestinal Neoplasms ; Humans ; Immune System ; *Microbiota ; }, abstract = {The human microbiome has been recognized as increasingly important to health and disease. This is especially prescient in the development of various cancers, their progression, and the microbiome's modulation of various anticancer therapeutics. Mechanisms behind these interactions have been increasingly well described through modulation of the host immune system as well as induction of genetic changes and local inactivation of cancer therapeutics. Here, we review these associations for a variety of gastrointestinal malignancies as well as contemporary strategies proposed to leverage these associations to improve cancer treatment outcomes.}, }
@article {pmid36151926, year = {2023}, author = {Pedro, N and Brucato, N and Cavadas, B and Lisant, V and Camacho, R and Kinipi, C and Leavesley, M and Pereira, L and Ricaut, FX}, title = {First insight into oral microbiome diversity in Papua New Guineans reveals a specific regional signature.}, journal = {Molecular ecology}, volume = {32}, number = {10}, pages = {2551-2564}, doi = {10.1111/mec.16702}, pmid = {36151926}, issn = {1365-294X}, mesh = {Humans ; Australia ; Geography ; *Microbiota/genetics ; Papua New Guinea ; *Mouth/microbiology ; }, abstract = {The oral microbiota is a highly complex and diversified part of the human microbiome. Being located at the interface between the human body and the exterior environment, this microbiota can deepen our understanding of the environmental impacts on the global status of human health. This research topic has been well addressed in Westernized populations, but these populations only represent a fraction of human diversity. Papua New Guinea hosts very diverse environments and one of the most unique human biological diversities worldwide. In this study we performed the first known characterization of the oral microbiome in 85 Papua New Guinean individuals living in different environments, using a qualitative and quantitative approach. We found a significant geographical structure of the Papua New Guineans oral microbiome, especially in the groups most isolated from urban spaces. In comparison to other global populations, two bacterial genera related to iron absorption were significantly more abundant in Papua New Guineans and Aboriginal Australians, which suggests a shared oral microbiome signature. Further studies will be needed to confirm and explore this possible regional-specific oral microbiome profile.}, }
@article {pmid36151873, year = {2022}, author = {Begum, N and Harzandi, A and Lee, S and Uhlen, M and Moyes, DL and Shoaie, S}, title = {Host-mycobiome metabolic interactions in health and disease.}, journal = {Gut microbes}, volume = {14}, number = {1}, pages = {2121576}, pmid = {36151873}, issn = {1949-0984}, support = {BB/S016899/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Fungi ; *Gastrointestinal Microbiome ; Humans ; Microbial Interactions ; *Microbiota ; *Mycobiome ; }, abstract = {Fungal communities (mycobiome) have an important role in sustaining the resilience of complex microbial communities and maintenance of homeostasis. The mycobiome remains relatively unexplored compared to the bacteriome despite increasing evidence highlighting their contribution to host-microbiome interactions in health and disease. Despite being a small proportion of the total species, fungi constitute a large proportion of the biomass within the human microbiome and thus serve as a potential target for metabolic reprogramming in pathogenesis and disease mechanism. Metabolites produced by fungi shape host niches, induce immune tolerance and changes in their levels prelude changes associated with metabolic diseases and cancer. Given the complexity of microbial interactions, studying the metabolic interplay of the mycobiome with both host and microbiome is a demanding but crucial task. However, genome-scale modelling and synthetic biology can provide an integrative platform that allows elucidation of the multifaceted interactions between mycobiome, microbiome and host. The inferences gained from understanding mycobiome interplay with other organisms can delineate the key role of the mycobiome in pathophysiology and reveal its role in human disease.}, }
@article {pmid36146653, year = {2022}, author = {Yutin, N and Rayko, M and Antipov, D and Mutz, P and Wolf, YI and Krupovic, M and Koonin, EV}, title = {Varidnaviruses in the Human Gut: A Major Expansion of the Order Vinavirales.}, journal = {Viruses}, volume = {14}, number = {9}, pages = {}, pmid = {36146653}, issn = {1999-4915}, support = {Intramural funds/NH/NIH HHS/United States ; }, mesh = {Adenosine Triphosphatases/genetics ; *Bacteriophages/genetics ; Capsid Proteins/genetics ; Humans ; Intestines ; Phylogeny ; Prophages/genetics ; *Viruses ; }, abstract = {Bacteriophages play key roles in the dynamics of the human microbiome. By far the most abundant components of the human gut virome are tailed bacteriophages of the realm Duplodnaviria, in particular, crAss-like phages. However, apart from duplodnaviruses, the gut virome has not been dissected in detail. Here we report a comprehensive census of a minor component of the gut virome, the tailless bacteriophages of the realm Varidnaviria. Tailless phages are primarily represented in the gut by prophages, that are mostly integrated in genomes of Alphaproteobacteria and Verrucomicrobia and belong to the order Vinavirales, which currently consists of the families Corticoviridae and Autolykiviridae. Phylogenetic analysis of the major capsid proteins (MCP) suggests that at least three new families should be established within Vinavirales to accommodate the diversity of prophages from the human gut virome. Previously, only the MCP and packaging ATPase genes were reported as conserved core genes of Vinavirales. Here we report an extended core set of 12 proteins, including MCP, packaging ATPase, and previously undetected lysis enzymes, that are shared by most of these viruses. We further demonstrate that replication system components are frequently replaced in the genomes of Vinavirales, suggestive of selective pressure for escape from yet unknown host defenses or avoidance of incompatibility with coinfecting related viruses. The results of this analysis show that, in a sharp contrast to marine viromes, varidnaviruses are a minor component of the human gut virome. Moreover, they are primarily represented by prophages, as indicated by the analysis of the flanking genes, suggesting that there are few, if any, lytic varidnavirus infections in the gut at any given time. These findings complement the existing knowledge of the human gut virome by exploring a group of viruses that has been virtually overlooked in previous work.}, }
@article {pmid36144238, year = {2022}, author = {Liu, M and Nieuwdorp, M and de Vos, WM and Rampanelli, E}, title = {Microbial Tryptophan Metabolism Tunes Host Immunity, Metabolism, and Extraintestinal Disorders.}, journal = {Metabolites}, volume = {12}, number = {9}, pages = {}, pmid = {36144238}, issn = {2218-1989}, support = {TKI-PPP Health-Holland, 2020//Top Consortia for Knowledge and Innovation (TKI-PPP) grant/ ; }, abstract = {The trillions of commensal microorganisms comprising the gut microbiota have received growing attention owing to their impact on host physiology. Recent advances in our understandings of the host-microbiota crosstalk support a pivotal role of microbiota-derived metabolites in various physiological processes, as they serve as messengers in the complex dialogue between commensals and host immune and endocrine cells. In this review, we highlight the importance of tryptophan-derived metabolites in host physiology, and summarize the recent findings on the role of tryptophan catabolites in preserving intestinal homeostasis and fine-tuning immune and metabolic responses. Furthermore, we discuss the latest evidence on the effects of microbial tryptophan catabolites, describe their mechanisms of action, and discuss how perturbations of microbial tryptophan metabolism may affect the course of intestinal and extraintestinal disorders, including inflammatory bowel diseases, metabolic disorders, chronic kidney diseases, and cardiovascular diseases.}, }
@article {pmid36143456, year = {2022}, author = {Olunoiki, E and Rehner, J and Bischoff, M and Koshel, E and Vogt, T and Reichrath, J and Becker, SL}, title = {Characteristics of the Skin Microbiome in Selected Dermatological Conditions: A Narrative Review.}, journal = {Life (Basel, Switzerland)}, volume = {12}, number = {9}, pages = {}, pmid = {36143456}, issn = {2075-1729}, abstract = {The skin is the largest and outermost organ of the human body. The microbial diversity of the skin can be influenced by several variable factors such as physiological state, lifestyle, and geographical locations. Recent years have seen increased interest in research aiming at an improved understanding of the relationship between the human microbiota and several diseases. Albeit understudied, interesting correlations between the skin microbiota and several dermatological conditions have been observed. Studies have shown that a decrease or increase in the abundance of certain microbial communities can be implicated in several dermatological pathologies. This narrative review (i) examines the role of the skin microbiota in the maintenance of skin homeostasis and health, (ii) provides examples on how some common skin diseases (acne inversa, candidiasis, psoriasis) are associated with the dysbiosis of microbial communities, and (iii) describes how recent research approaches used in skin microbiome studies may lead to improved, more sensitive diagnostics and individual therapeutics in the foreseeable future.}, }
@article {pmid36142163, year = {2022}, author = {Del Chierico, F and Conta, G and Matteoli, MC and Fierabracci, A and Reddel, S and Macari, G and Gardini, S and Guarrasi, V and Levi Mortera, S and Marzano, V and Vernocchi, P and Sciubba, F and Marini, F and Deodati, A and Rapini, N and Cianfarani, S and Miccheli, A and Putignani, L}, title = {Gut Microbiota Functional Traits, Blood pH, and Anti-GAD Antibodies Concur in the Clinical Characterization of T1D at Onset.}, journal = {International journal of molecular sciences}, volume = {23}, number = {18}, pages = {}, pmid = {36142163}, issn = {1422-0067}, support = {Ricerca Corrente 2017, 2018, 2019 and 5 &#x2030; 2020, assigned to LP//Italian Ministry of Health/ ; }, mesh = {Biomarkers/metabolism ; Clostridiales/metabolism ; *Diabetes Mellitus, Type 1 ; *Gastrointestinal Microbiome ; Humans ; Hydrogen-Ion Concentration ; Isobutyrates ; Malonates ; Purines ; Pyrimidines ; RNA, Ribosomal, 16S/genetics ; }, abstract = {Alterations of gut microbiota have been identified before clinical manifestation of type 1 diabetes (T1D). To identify the associations amongst gut microbiome profile, metabolism and disease markers, the 16S rRNA-based microbiota profiling and [1]H-NMR metabolomic analysis were performed on stool samples of 52 T1D patients at onset, 17 T1D siblings and 57 healthy subjects (CTRL). Univariate, multivariate analyses and classification models were applied to clinical and -omic integrated datasets. In T1D patients and their siblings, Clostridiales and Dorea were increased and Dialister and Akkermansia were decreased compared to CTRL, while in T1D, Lachnospiraceae were higher and Collinsella was lower, compared to siblings and CTRL. Higher levels of isobutyrate, malonate, Clostridium, Enterobacteriaceae, Clostridiales, Bacteroidales, were associated to T1D compared to CTRL. Patients with higher anti-GAD levels showed low abundances of Roseburia, Faecalibacterium and Alistipes and those with normal blood pH and low serum HbA1c levels showed high levels of purine and pyrimidine intermediates. We detected specific gut microbiota profiles linked to both T1D at the onset and to diabetes familiarity. The presence of specific microbial and metabolic profiles in gut linked to anti-GAD levels and to blood acidosis can be considered as predictive biomarker associated progression and severity of T1D.}, }
@article {pmid36140010, year = {2022}, author = {Riva, V and Patania, G and Riva, F and Vergani, L and Crotti, E and Mapelli, F}, title = {Acinetobacter baylyi Strain BD413 Can Acquire an Antibiotic Resistance Gene by Natural Transformation on Lettuce Phylloplane and Enter the Endosphere.}, journal = {Antibiotics (Basel, Switzerland)}, volume = {11}, number = {9}, pages = {}, pmid = {36140010}, issn = {2079-6382}, support = {2018-0995//Fondazione Cariplo/ ; }, abstract = {Antibiotic resistance spread must be considered in a holistic framework which comprises the agri-food ecosystems, where plants can be considered a bridge connecting water and soil habitats with the human microbiome. However, the study of horizontal gene transfer events within the plant microbiome is still overlooked. Here, the environmental strain Acinetobacter baylyi BD413 was used to study the acquisition of extracellular DNA (exDNA) carrying an antibiotic resistance gene (ARG) on lettuce phylloplane, performing experiments at conditions (i.e., plasmid quantities) mimicking those that can be found in a water reuse scenario. Moreover, we assessed how the presence of a surfactant, a co-formulant widely used in agriculture, affected exDNA entry in bacteria and plant tissues, besides the penetration and survival of bacteria into the leaf endosphere. Natural transformation frequency in planta was comparable to that occurring under optimal conditions (i.e., temperature, nutrient provision, and absence of microbial competitors), representing an entrance pathway of ARGs into an epiphytic bacterium able to penetrate the endosphere of a leafy vegetable. The presence of the surfactant determined a higher presence of culturable transformant cells in the leaf tissues but did not significantly increase exDNA entry in A. baylyi BD413 cells and lettuce leaves. More research on HGT (Horizontal Gene Transfer) mechanisms in planta should be performed to obtain experimental data on produce safety in terms of antibiotic resistance.}, }
@article {pmid36130094, year = {2022}, author = {Smith, C and Van Haute, MJ and Xian, Y and Segura Munoz, RR and Liu, S and Schmaltz, RJ and Ramer-Tait, AE and Rose, DJ}, title = {Carbohydrate utilization by the gut microbiome determines host health responsiveness to whole grain type and processing methods.}, journal = {Gut microbes}, volume = {14}, number = {1}, pages = {2126275}, pmid = {36130094}, issn = {1949-0984}, mesh = {Animals ; Blood Glucose ; Diet ; Edible Grain/metabolism ; Fatty Acids, Volatile ; *Gastrointestinal Microbiome ; Humans ; Mice ; Triticum/metabolism ; *Whole Grains ; }, abstract = {Little is known about how interactions among grain processing, grain type, and carbohydrate utilization (CU) by the microbiome influence the health benefits of whole grains. Therefore, two whole grains - brown rice and whole wheat - and two processing methods - boiling (porridge) and extrusion - were studied for their effects on host metabolic outcomes in mice harboring human microbiomes previously shown in vitro to have high or low CU. Mice carrying either microbiome experienced increases in body weight and glycemia when consuming Western diets supplemented with extruded grains versus porridge. However, mice with the high but not low CU microbiome also gained more weight and fat over time and were less glucose tolerant when consuming extruded grain diets. In high CU microbiome mice, the exacerbated negative health outcomes associated with extrusion were related to altered abundances of Lachnospiraceae and Ruminococcaceae as well as elevated sugar degradation and colonic acetate production. The amplicon sequence variants (ASVs) associated with extruded and porridge diets in this in vivo study were not the same as those identified in our prior in vitro study; however, the predicted functions were highly correlated. In conclusion, mice harboring both high and low CU microbiomes responded to the whole grain diets similarly, except the high CU microbiome mice exhibited exacerbated effects due to excessive acetate production, indicating that CU by the microbiome is linked to host metabolic health outcomes. Our work demonstrates that a greater understanding of food processing effects on the microbiome is necessary for developing foods that promote rather than diminish host health.Abbreviations: CU- carbohydrate utilization; SCFA- short-chain fatty acids; GF- germ-free; HMA, human-microbiome associated; ipGTT- intraperitoneal glucose tolerance test; HOMA-IR- Homeostatic Model Assessment for Insulin Resistance; AUC- area under the glycemia curve; ASV- amplicon sequence variant; lf- low-fat; wd- Western diet; wd_wwp- Western diet containing whole wheat porridge; wd_wwe- Western diet containing whole wheat extrudate; wd_bre- Western diet containing brown rice extrudate; wd_extr- Western diet containing either whole wheat or brown rice extrudate.}, }
@article {pmid36127929, year = {2022}, author = {Mao, J and Ma, LI}, title = {DIRICHLET-TREE MULTINOMIAL MIXTURES FOR CLUSTERING MICROBIOME COMPOSITIONS.}, journal = {The annals of applied statistics}, volume = {16}, number = {3}, pages = {1476-1499}, pmid = {36127929}, issn = {1932-6157}, support = {R01 GM135440/GM/NIGMS NIH HHS/United States ; }, abstract = {Studying the human microbiome has gained substantial interest in recent years, and a common task in the analysis of these data is to cluster microbiome compositions into subtypes. This subdivision of samples into subgroups serves as an intermediary step in achieving personalized diagnosis and treatment. In applying existing clustering methods to modern microbiome studies including the American Gut Project (AGP) data, we found that this seemingly standard task, however, is very challenging in the microbiome composition context due to several key features of such data. Standard distance-based clustering algorithms generally do not produce reliable results as they do not take into account the heterogeneity of the cross-sample variability among the bacterial taxa, while existing model-based approaches do not allow sufficient flexibility for the identification of complex within-cluster variation from cross-cluster variation. Direct applications of such methods generally lead to overly dispersed clusters in the AGP data and such phenomenon is common for other microbiome data. To overcome these challenges, we introduce Dirichlet-tree multinomial mixtures (DTMM) as a Bayesian generative model for clustering amplicon sequencing data in microbiome studies. DTMM models the microbiome population with a mixture of Dirichlet-tree kernels that utilizes the phylogenetic tree to offer a more flexible covariance structure in characterizing within-cluster variation, and it provides a means for identifying a subset of signature taxa that distinguish the clusters. We perform extensive simulation studies to evaluate the performance of DTMM and compare it to state-of-the-art model-based and distance-based clustering methods in the microbiome context, and carry out a validation study on a publicly available longitudinal data set to confirm the biological relevance of the clusters. Finally, we report a case study on the fecal data from the AGP to identify compositional clusters among individuals with inflammatory bowel disease and diabetes. Among our most interesting findings is that enterotypes (i.e., gut microbiome clusters) are not always defined by the most dominant species as previous analyses had assumed, but can involve a number of less abundant OTUs, which cannot be identified with existing distance-based and method-based approaches.}, }
@article {pmid36111766, year = {2023}, author = {Askari, H and Shojaei-Zarghani, S and Raeis-Abdollahi, E and Jahromi, HK and Abdullahi, PR and Daliri, K and Tajbakhsh, A and Rahmati, L and Safarpour, AR}, title = {The Role of Gut Microbiota in Inflammatory Bowel Disease-Current State of the Art.}, journal = {Mini reviews in medicinal chemistry}, volume = {23}, number = {13}, pages = {1376-1389}, doi = {10.2174/1389557522666220914093331}, pmid = {36111766}, issn = {1875-5607}, mesh = {Humans ; *Gastrointestinal Microbiome ; Dysbiosis/complications/microbiology ; *Inflammatory Bowel Diseases ; Inflammation/complications ; *MicroRNAs/genetics ; }, abstract = {The human microbiome comprises the genomes of the microbiota that live on and within humans, such as protozoa, archaea, eukaryotes, viruses, and most bacteria. Gastrointestinal disorders such as inflammatory bowel disease, colon cancer, celiac disease, and irritable bowel syndrome can all be triggered by a change in gut flora. The alteration of the gut microbiota (also known as "gut dysbiosis") is affected by host genetics, nutrition, antibiotics, and inflammation, and it is associated with the development of inflammatory bowel disease (IBD). Also, intestinal epithelial dysfunction, altered autophagy, and immune hyperactivation are frequently detected in individuals with severe IBD, which may be attributed to impaired miRNA expression functions. While the exact mechanisms of how Gut Microbiota may cause IBD and intestinal epithelial dysfunction are still debated, recent data point toward the possibility that hormones, gender and miRNAs expression are modifiable contributors to IBD. This review summarizes the current evidence for an association between hormones, gender and miRNAs and Gut Microbiota in IBD and discusses potential mechanisms by which gut microbiota may impact IBD. The study also outlines critical unanswered topics that need to be solved to enhance IBD prevention and treatment in people with gut dysbiosis.}, }
@article {pmid36109831, year = {2022}, author = {Roussel, C and Anunciação Braga Guebara, S and Plante, PL and Desjardins, Y and Di Marzo, V and Silvestri, C}, title = {Short-term supplementation with ω-3 polyunsaturated fatty acids modulates primarily mucolytic species from the gut luminal mucin niche in a human fermentation system.}, journal = {Gut microbes}, volume = {14}, number = {1}, pages = {2120344}, pmid = {36109831}, issn = {1949-0984}, mesh = {Akkermansia ; Docosahexaenoic Acids/pharmacology ; Eicosapentaenoic Acid/pharmacology ; Expectorants/pharmacology ; *Fatty Acids, Omega-3/pharmacology ; Fatty Acids, Volatile ; Fermentation ; Firmicutes ; *Gastrointestinal Microbiome ; Humans ; *Microbiota ; Mucins ; Prebiotics ; Propionates/pharmacology ; Verrucomicrobia ; }, abstract = {Consumption of omega-3 polyunsaturated fatty acids (ω-3 PUFAs) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) provides multifaceted health benefits. Recent studies suggest that ω-3 PUFAs modulate the gut microbiota by enhancing health-promoting bacteria, such as the mucin specialist Akkermansia muciniphila. However, these prebiotic properties have been poorly investigated and direct effects on the gut microbiome have never been explored dynamically across gut regions and niches (lumen vs. mucus-associated microbiota). Thus, we studied the effects of 1 week EPA- and DHA-enriched ω-3 fish-oil supplementation on the composition and functionality of the human microbiome in a Mucosal Simulator of the Human Intestinal Microbial Ecosystem (M-SHIME®). Gut microbial communities derived from one individual harvested in two different seasons were tested in duplicate. Luminal and outer mucus-associated microbiota of the ileum, ascending, transverse and descending colons were cultivated over 28 d from fecal inoculates and supplemented with ω-3 PUFAs for the last 7 d. We show that ω-3 PUFA supplementation modulates the microbiota in a gut region- and niche-dependent fashion. The outer mucus-associated microbiota displayed a higher resilience than the luminal mucin habitat to ω-3 PUFAs, with a remarkable blooming of Akkermansia muciniphila in opposition to a decrease of Firmicutes-mucolytic bacteria. The ω-3 PUFAs also induced a gradual and significant depletion of non-mucolytic Clostridia members in luminal habitats. Finally, increased concentrations of the short chain fatty acids (SCFA) propionate in colon regions at the end of the supplementation was associated positively with the bloom of Akkermansia muciniphila and members of the Desulfovibrionia class.}, }
@article {pmid36109637, year = {2022}, author = {Ianiro, G and Punčochář, M and Karcher, N and Porcari, S and Armanini, F and Asnicar, F and Beghini, F and Blanco-Míguez, A and Cumbo, F and Manghi, P and Pinto, F and Masucci, L and Quaranta, G and De Giorgi, S and Sciumè, GD and Bibbò, S and Del Chierico, F and Putignani, L and Sanguinetti, M and Gasbarrini, A and Valles-Colomer, M and Cammarota, G and Segata, N}, title = {Variability of strain engraftment and predictability of microbiome composition after fecal microbiota transplantation across different diseases.}, journal = {Nature medicine}, volume = {28}, number = {9}, pages = {1913-1923}, pmid = {36109637}, issn = {1546-170X}, support = {R01 CA230551/CA/NCI NIH HHS/United States ; U01 CA230551/CA/NCI NIH HHS/United States ; }, mesh = {Anti-Bacterial Agents ; *Clostridium Infections/microbiology/therapy ; Fecal Microbiota Transplantation/methods ; Feces/microbiology ; *Gastrointestinal Microbiome ; Humans ; *Microbiota ; Treatment Outcome ; }, abstract = {Fecal microbiota transplantation (FMT) is highly effective against recurrent Clostridioides difficile infection and is considered a promising treatment for other microbiome-related disorders, but a comprehensive understanding of microbial engraftment dynamics is lacking, which prevents informed applications of this therapeutic approach. Here, we performed an integrated shotgun metagenomic systematic meta-analysis of new and publicly available stool microbiomes collected from 226 triads of donors, pre-FMT recipients and post-FMT recipients across eight different disease types. By leveraging improved metagenomic strain-profiling to infer strain sharing, we found that recipients with higher donor strain engraftment were more likely to experience clinical success after FMT (P = 0.017) when evaluated across studies. Considering all cohorts, increased engraftment was noted in individuals receiving FMT from multiple routes (for example, both via capsules and colonoscopy during the same treatment) as well as in antibiotic-treated recipients with infectious diseases compared with antibiotic-naïve patients with noncommunicable diseases. Bacteroidetes and Actinobacteria species (including Bifidobacteria) displayed higher engraftment than Firmicutes except for six under-characterized Firmicutes species. Cross-dataset machine learning predicted the presence or absence of species in the post-FMT recipient at 0.77 average AUROC in leave-one-dataset-out evaluation, and highlighted the relevance of microbial abundance, prevalence and taxonomy to infer post-FMT species presence. By exploring the dynamics of microbiome engraftment after FMT and their association with clinical variables, our study uncovered species-specific engraftment patterns and presented machine learning models able to predict donors that might optimize post-FMT specific microbiome characteristics for disease-targeted FMT protocols.}, }
@article {pmid36109636, year = {2022}, author = {Schmidt, TSB and Li, SS and Maistrenko, OM and Akanni, W and Coelho, LP and Dolai, S and Fullam, A and Glazek, AM and Hercog, R and Herrema, H and Jung, F and Kandels, S and Orakov, A and Thielemann, R and von Stetten, M and Van Rossum, T and Benes, V and Borody, TJ and de Vos, WM and Ponsioen, CY and Nieuwdorp, M and Bork, P}, title = {Drivers and determinants of strain dynamics following fecal microbiota transplantation.}, journal = {Nature medicine}, volume = {28}, number = {9}, pages = {1902-1912}, pmid = {36109636}, issn = {1546-170X}, mesh = {*Clostridium Infections/therapy ; Fecal Microbiota Transplantation ; Feces ; *Gastrointestinal Microbiome/genetics ; Gastrointestinal Tract ; Humans ; *Microbiota ; }, abstract = {Fecal microbiota transplantation (FMT) is a therapeutic intervention for inflammatory diseases of the gastrointestinal tract, but its clinical mode of action and subsequent microbiome dynamics remain poorly understood. Here we analyzed metagenomes from 316 FMTs, sampled pre and post intervention, for the treatment of ten different disease indications. We quantified strain-level dynamics of 1,089 microbial species, complemented by 47,548 newly constructed metagenome-assembled genomes. Donor strain colonization and recipient strain resilience were mostly independent of clinical outcomes, but accurately predictable using LASSO-regularized regression models that accounted for host, microbiome and procedural variables. Recipient factors and donor-recipient complementarity, encompassing entire microbial communities to individual strains, were the main determinants of strain population dynamics, providing insights into the underlying processes that shape the post-FMT gut microbiome. Applying an ecology-based framework to our findings indicated parameters that may inform the development of more effective, targeted microbiome therapies in the future, and suggested how patient stratification can be used to enhance donor microbiota colonization or the displacement of recipient microbes in clinical practice.}, }
@article {pmid36109427, year = {2023}, author = {Nidhi, S and Tripathi, P and Tripathi, V}, title = {Phylogenetic Analysis of Anti-CRISPR and Member Addition in the Families.}, journal = {Molecular biotechnology}, volume = {65}, number = {2}, pages = {273-281}, pmid = {36109427}, issn = {1559-0305}, mesh = {Humans ; Phylogeny ; *Bacteria/genetics ; *Bacteriophages/genetics ; Metagenome ; CRISPR-Cas Systems ; }, abstract = {CRISPR-Cas is a widespread anti-viral adaptive immune system in the microorganisms. Viruses living in bacteria or some phages carry anti-CRISPR proteins to evade immunity by CRISPR-Cas. The anti-CRISPR proteins are prevalent in phages capable of lying dormant in a CRISPR-carrying host, while their orthologs frequently found in virulent phages. Here, we propose a probabilistic strategy of ancestral sequence reconstruction (ASR) and Hidden Markov Model (HMM) profile search to fish out sequences of anti-CRISPR proteins from environmental metagenomic, human microbiome metagenomic, human microbiome reference genome, and NCBI's non-redundant databases. Our results revealed that the metagenome database dark matter might contain anti-CRISPR encoding genes.}, }
@article {pmid36108037, year = {2022}, author = {Schul, M and Mason, A and Ushijima, B and Sneed, JM}, title = {Microbiome and Metabolome Contributions to Coral Health and Disease.}, journal = {The Biological bulletin}, volume = {243}, number = {1}, pages = {76-83}, doi = {10.1086/720971}, pmid = {36108037}, issn = {1939-8697}, mesh = {Animals ; *Anthozoa ; Anti-Bacterial Agents ; Bacteria ; *Biological Products ; Humans ; Metabolome ; *Microbiota ; }, abstract = {AbstractCoral populations are declining worldwide as a result of increased environmental stressors, including disease. Coral health is greatly dependent on complex interactions between the host animal and its associated microbial symbionts. While relatively understudied, there is growing evidence that the coral microbiome contributes to the health and resilience of corals in a variety of ways, similar to more well-studied systems, such as the human microbiome. Many of these interactions are dependent upon the production and exchange of natural products, including antibacterial compounds, quorum-sensing molecules, internal signaling molecules, nutrients, and so on. While advances in sequencing, culturing, and metabolomic techniques have aided in moving forward the understanding of coral microbiome interactions, current sequence and metabolite databases are lacking, hindering detailed descriptions of the microbes and metabolites involved. This review focuses on the roles of coral microbiomes in health and disease processes of coral hosts, with special attention to the coral metabolome. We discuss what is currently known about the relationship between the coral microbiome and disease, of beneficial microbial products or services, and how the manipulation of the coral microbiome may chemically benefit the coral host against disease. Understanding coral microbiome-metabolome interactions is critical to assisting management, conservation, and restoration strategies.}, }
@article {pmid36103827, year = {2022}, author = {Wang, X and Pang, K and Wang, J and Zhang, B and Liu, Z and Lu, S and Xu, X and Zhu, L and Zhou, Z and Niu, M and Gao, J and Li, J and Zhao, F and Wu, J}, title = {Microbiota dysbiosis in primary Sjögren's syndrome and the ameliorative effect of hydroxychloroquine.}, journal = {Cell reports}, volume = {40}, number = {11}, pages = {111352}, doi = {10.1016/j.celrep.2022.111352}, pmid = {36103827}, issn = {2211-1247}, mesh = {Dysbiosis/complications/drug therapy/microbiology ; Female ; *Gastrointestinal Microbiome/genetics ; Humans ; Hydroxychloroquine/pharmacology/therapeutic use ; *Microbiota ; RNA, Ribosomal, 16S/genetics ; *Sjogren's Syndrome/complications/drug therapy ; }, abstract = {The human microbiome plays an important role in autoimmune diseases. However, there is limited knowledge regarding the microbiota in individuals with primary Sjögren's syndrome (pSS). Here, we perform 16S ribosomal RNA gene sequencing of fecal, oral, and vaginal samples from a cohort of 133 individuals with pSS, 56 with non-pSS, and 40 healthy control (HC) individuals. Dysbiosis in the gut, oral, and vaginal microbiome is evident in patients with pSS, and oral samples demonstrate the greatest extent of microbial variation. Multiple key indicator bacteria and clinical characteristics are identified across different body sites, implying that microbial dysbiosis has important roles in the pathogenesis of pSS. Furthermore, we observe pSS-like dysbiosis in individuals with pre-clinical pSS or non-pSS-related disease, revealing that microbial shifts could appear prior to pSS. After hydroxychloroquine (HCQ) treatment, microbial dysbiosis in individuals with pSS is partially resolved, although the microbiota composition remain disordered. These results contribute to the overall understanding of the relationship between the microbiome and pSS.}, }
@article {pmid36103557, year = {2022}, author = {Wikström, T and Abrahamsson, S and Bengtsson-Palme, J and Ek, J and Kuusela, P and Rekabdar, E and Lindgren, P and Wennerholm, UB and Jacobsson, B and Valentin, L and Hagberg, H}, title = {Microbial and human transcriptome in vaginal fluid at midgestation: Association with spontaneous preterm delivery.}, journal = {Clinical and translational medicine}, volume = {12}, number = {9}, pages = {e1023}, pmid = {36103557}, issn = {2001-1326}, mesh = {Bacteria ; Bodily Secretions ; *Body Fluids ; Female ; Humans ; Infant, Newborn ; Pregnancy ; *Premature Birth/epidemiology/genetics ; Transcriptome/genetics ; Vagina/microbiology ; }, abstract = {BACKGROUND: Intrauterine infection and inflammation caused by microbial transfer from the vagina are believed to be important factors causing spontaneous preterm delivery (PTD). Multiple studies have examined the relationship between the cervicovaginal microbiome and spontaneous PTD with divergent results. Most studies have applied a DNA-based assessment, providing information on the microbial composition but not transcriptional activity. A transcriptomic approach was applied to investigate differences in the active vaginal microbiome and human transcriptome at midgestation between women delivering spontaneously preterm versus those delivering at term.<br><br>METHODS: Vaginal swabs were collected in women with a singleton pregnancy at 18 + 0 to 20 + 6 gestational weeks. For each case of spontaneous PTD (delivery&#xa0;<37 + 0&#xa0;weeks) two term controls were randomized (39 + 0 to 40 + 6&#xa0;weeks). Vaginal specimens were subject to sequencing of both human and microbial RNA. Microbial reads were taxonomically classified using Kraken2 and RefSeq as a reference. Statistical analyses were performed using DESeq2. GSEA and HUMAnN3 were used for pathway analyses.<br><br>RESULTS: We found 17 human genes to be differentially expressed (false discovery rate, FDR&#xa0;<&#xa0;0.05) in the preterm group (n =&#xa0;48) compared to the term group (n =&#xa0;96). Gene expression of kallikrein-2 (KLK2), KLK3 and four isoforms of metallothioneins 1 (MT1s) was higher in the preterm group (FDR&#xa0;<&#xa0;0.05). We found 11 individual bacterial species to be differentially expressed (FDR&#xa0;<&#xa0;0.05), most with a low occurrence. No statistically significant differences in bacterial load, diversity or microbial community state types were found between the groups.<br><br>CONCLUSIONS: In our mainly white population, primarily bacterial species of low occurrence were differentially expressed at midgestation in women who delivered preterm versus at term. However, the expression of specific human transcripts including KLK2, KLK3 and several isoforms of MT1s was higher in preterm cases. This is of interest, because these genes may be involved in critical inflammatory pathways associated with spontaneous PTD.}, }
@article {pmid36101364, year = {2022}, author = {Loiko, N and Kanunnikov, O and Gannesen, A and Kovalenko, V and Vishnyakova, A and Axelrod, V and Litti, Y}, title = {Brain Natriuretic Peptide (BNP) Affects Growth and Stress Tolerance of Representatives of the Human Microbiome, Micrococcus luteus C01 and Alcaligenes faecalis DOS7.}, journal = {Biology}, volume = {11}, number = {7}, pages = {}, pmid = {36101364}, issn = {2079-7737}, support = {19-74-10071//Russian Science Foundation/ ; 122040800164-6//Ministry of Science and Higher Education of the Russian Federation/ ; 122040400089-6//FIC CP RAS FFZE-2022-0011/ ; }, abstract = {Brain natriuretic peptide (BNP) is secreted by the ventricles of the heart during overload to signal heart failure. Slight bilateral skin itching induced by BNP has been associated with response activity of the skin microbiota. In this work, we studied the effect of 25-250,000 pg BNP/mL on the growth, long-term survival, and stress (H2O2, antibiotics, salinity, heat and pH shock) resistance of human symbiont bacteria: Gram-positive Micrococcus luteus C01 and Gram-negative Alcaligenes faecalis DOS7. The effect of BNP turned out to be dose-dependent. Up to 250 pg BNP/mL made bacteria more stress resistant. At 2500 pg BNP/mL (heart failure) the thermosensitivity of the bacteria increased. Almost all considered BNP concentrations increased the resistance of bacteria to the action of tetracycline and ciprofloxacin. Both bacteria survived 1.3-1.7 times better during long-term (up to 4 months) storage. Our findings are important both for clinical medical practice and for practical application in other areas. For example, BNP can be used to obtain stress-resistant bacteria, which is important in the collection of microorganisms, as well as for the production of bacterial preparations and probiotics for cosmetology, agriculture, and waste management.}, }
@article {pmid36099461, year = {2022}, author = {Mangutov, EO and Alieva, AA and Kharseeva, GG and Voronina, NA and Alekseeva, LP and Evdokimova, VV and Yakusheva, OA and Popivnenko, MD}, title = {Corynebacterium spp.: relationship of pathogenic properties and antimicrobial resistance.}, journal = {Klinicheskaia laboratornaia diagnostika}, volume = {67}, number = {9}, pages = {519-524}, doi = {10.51620/0869-2084-2022-67-9-519-524}, pmid = {36099461}, issn = {0869-2084}, mesh = {Anti-Bacterial Agents/pharmacology/therapeutic use ; *Anti-Infective Agents/pharmacology ; Corynebacterium ; *Corynebacterium Infections/drug therapy/microbiology ; Drug Resistance, Bacterial/genetics ; Humans ; }, abstract = {Corynebacterium spp. are part of the human microbiome, but can cause the development of inflammatory diseases of various localization. Purpose - to evaluate the relationship between pathogenic properties and resistance to antimicrobial drugs (AMD) of Corynebacterium spp. from patients with inflammatory diseases of the respiratory tract. Strains of Corynebacterium spp. isolated from patients with inflammatory diseases of the respiratory tract (99 pcs.) and practically healthy individuals (33 pcs.). Isolates were identified by mass spectrometric method (MALDI-ToFMS), their adhesive and invasive activity on Hep-2 cells, cytopathic effect (CPE) in CHO-K1 cell culture, and resistance to antimicrobial drugs (AMD) were determined. Indicators of adhesion (3.65±0.679(CFU±m)x102/ml), invasion (1.72±0.230 (CFU±m)x102/ml), cytotoxicity (69.1±3.8% of dead CHO-K1 cells) Corynebasterium spp. strains isolated from patients are higher (p≤0.05) than similar indicators in practically healthy people. 90.9% of isolates from patients had resistance to AMD, in most cases (57.6±4.9%) resistance to only one AMP was noted, less often to two (25.2±4.3%), three or more (8.08±2.7%). According to the results of correlation-regression analysis, pathogenic properties (adhesiveness, invasiveness, cytotoxicity) of Corynebacterium spp. strains isolated from patients are in close direct relationship with resistance to AMD. This indicates the importance of identifying strains of non-diphtheria corynebacteria resistant to AMDs, which, under the influence of developing resistance to AMDs, can increase their pathogenic potential, moving from commensalism to parasitism.}, }
@article {pmid36098525, year = {2022}, author = {Wang, Y and Guo, A and Liu, Z and Zou, Y and Zhu, W and Wu, S and Zhang, S and Guo, X and Zhang, S and Pu, L and Zhu, XQ and Zhu, G and Cai, X and Wang, S}, title = {Expansion of Opportunistic Enteric Fungal Pathogens and Occurrence of Gut Inflammation in Human Liver Echinococcosis.}, journal = {Microbiology spectrum}, volume = {10}, number = {5}, pages = {e0145322}, pmid = {36098525}, issn = {2165-0497}, mesh = {Humans ; Candida ; *Dysbiosis/microbiology ; *Echinococcosis/complications ; Feces/microbiology ; Fungi ; Inflammation ; Leukocyte L1 Antigen Complex ; Liver ; Aspergillus ; *Opportunistic Infections/microbiology ; }, abstract = {Increasing evidence shows that the gut fungal mycobiota is implicated in human disease. However, its relationship with chronic helminth infections, which cause immunosuppression and affect over 1 billion people worldwide, remains unexplored. In this study, we investigated the gut mycobiome and its associations with gut homeostasis in a severe helminth disease worldwide: liver echinococcosis. Fecal samples from 63 patients and 42 healthy controls were collected to characterize the fungal signatures using ITS1 sequencing, QIIME pipeline, and machine learning analysis. The levels of fecal calprotectin and serological anti-Saccharomyces cerevisiae antibodies (ASCA) in these subjects were experimentally measured. We found that fungal microbiota was significantly skewed in disease, with an overrepresentation of Aspergillus, Candida, Geotrichum, Kazachstania, and Penicillium and a decrease of Fusarium. Machine learning analysis revealed that the altered fungal features could efficiently predict infection with high sensitivity and specificity (area under the curve [AUC] = 0.93). The dysbiosis was characterized by expansions of multiple opportunistic pathogens (Aspergillus spp. and Candida spp.). Clinical association analysis revealed that host immunity might link to the expansions of the invasive fungi. Accompanying the opportunistic pathogen expansion, the levels of fungi-associated fecal calprotectin and serological ASCA in the patients were elevated, suggesting that gut inflammation and microbiota translocation occurred in this generally assumed extraintestinal disease. This study highlights enteric fungal pathogen expansions and increased levels of markers for fungi-associated mucosal inflammation and intestinal permeability as hallmarks of liver echinococcosis. IMPORTANCE Helminth infection affects over 1 billion people worldwide. However, its relationship with the gut mycobiome remains unknown. Among the most prevalent helminth diseases, human hydatid disease (echinococcosis) is highlighted as one of the most important (second/third for alveolar/cystic echinococcosis) foodborne parasitic diseases at the global level. Herein, we investigated the mycobiome and gut homeostasis (i.e., inflammation and permeability) in human echinococcosis. Our results revealed that fungal dysbiosis with an expansion of opportunistic pathogens and increased levels of fecal calprotectin and serum ASCA are hallmarks of human liver echinococcosis. Host immunity is associated with enteric fungal expansions. These findings suggest that an extraintestinal helminth infection is able to alter gut fungal microbiota and impair gut homeostasis, which resembles concomitant gut symptoms in inflammatory gut-related diseases (e.g., AIDS). In clinical practice, physicians need to take cautious medical consideration of gut health for nonintestinal helminth diseases.}, }
@article {pmid36094440, year = {2024}, author = {Baky, MH and Salah, M and Ezzelarab, N and Shao, P and Elshahed, MS and Farag, MA}, title = {Insoluble dietary fibers: structure, metabolism, interactions with human microbiome, and role in gut homeostasis.}, journal = {Critical reviews in food science and nutrition}, volume = {64}, number = {7}, pages = {1954-1968}, doi = {10.1080/10408398.2022.2119931}, pmid = {36094440}, issn = {1549-7852}, mesh = {Humans ; *Microbiota ; *Gastrointestinal Microbiome ; Homeostasis ; *Probiotics ; Dietary Fiber/metabolism ; }, abstract = {Consumption of food rich in dietary fibers (DFs) has been long recognized to exert an overall beneficial effect on human health. This review aims to provide a holistic overview on how IDFs impact human gut health either directly, or through modulation of the gut microbiome. Several databases were searched for collecting papers such as PubMed, Google Scholar, Web of Science, Scopus and Reaxys from 2000 till 2022. Firstly, an overview of the chemical structure of the various IDFs and the pathways employed by gut microbiota for their degradation is provided. The impact of IDFs on microbial community structure and pathogens colonization inside the human gut was discussed. Finally, the impact of IDFs on gut homeostasis and systemic effects at the cellular level, as well as the overall immunological benefits of IDFs consumption were analyzed. IDFs viz., cellulose, hemicellulose, resistant starch, and lignin found enriched in food are discussed for these effects. IDFs were found to induce gut immunity, improve intestinal integrity and mucosal proliferation, and favor adhesion of probiotics and hence improve human health. Also, IDFs were concluded to improve the bioavailability of plant polyphenols and improve their health-related functional roles. Ultimately, dietary fibers processing by modification shows potential to enhance fibers-based functional food production, in addition to increase the economic value and usage of food-rich fibers and their by-products.}, }
@article {pmid36093611, year = {2022}, author = {Korpela, K and de Vos, WM}, title = {Infant gut microbiota restoration: state of the art.}, journal = {Gut microbes}, volume = {14}, number = {1}, pages = {2118811}, pmid = {36093611}, issn = {1949-0984}, mesh = {Anti-Bacterial Agents ; Cesarean Section ; Female ; *Gastrointestinal Microbiome ; Humans ; Infant ; Pregnancy ; }, abstract = {The gut microbiota has a central role in the programming of the host's metabolism and immune function, with both immediate and long-term health consequences. Recent years have witnessed an accumulation of understanding of the process of the colonization and development of the gut microbiota in infants. The natural gut microbiota colonization during birth is frequently disrupted due to C-section birth or intrapartum or postpartum antibiotic exposure, and consequently aberrant gut microbiota development is common. On a positive note, research has shown that restoration of normal gut microbiota development is feasible. We discuss here the current understanding of the infant microbiota, provide an overview of the sources of disturbances, and critically evaluate the evidence on early life gut microbiota restoration for improved health outcomes by analyzing published data from infant gut microbiota restoration studies.}, }
@article {pmid36088157, year = {2022}, author = {Czibulka, A}, title = {Probiotics for Otolaryngologic Disorders.}, journal = {Otolaryngologic clinics of North America}, volume = {55}, number = {5}, pages = {939-946}, doi = {10.1016/j.otc.2022.06.003}, pmid = {36088157}, issn = {1557-8259}, mesh = {Diet ; Humans ; *Otolaryngology ; *Otorhinolaryngologic Diseases/therapy ; *Probiotics/therapeutic use ; }, abstract = {Chronic low-level inflammation is a causative factor in many of our common diseases. Switching to an anti-inflammatory diet is an important step that patients can take in for rectifying this risk factor. In this review, the author discusses the essential components of an anti-inflammatory diet and its contribution not only to the overall well-being but also to the body's defense against disease. The human microbiome is reviewed in detail and dietary connections and recommendations are explained for several otolaryngologic conditions.}, }
@article {pmid36087619, year = {2022}, author = {Wang, S and Kang, X and Alenius, H and Wong, SH and Karisola, P and El-Nezami, H}, title = {Oral exposure to Ag or TiO2 nanoparticles perturbed gut transcriptome and microbiota in a mouse model of ulcerative colitis.}, journal = {Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association}, volume = {169}, number = {}, pages = {113368}, doi = {10.1016/j.fct.2022.113368}, pmid = {36087619}, issn = {1873-6351}, mesh = {Animals ; Mice ; *Colitis, Ulcerative/chemically induced/metabolism ; *Colon/drug effects/microbiology ; Dextran Sulfate ; Disease Models, Animal ; Mice, Inbred C57BL ; RNA/metabolism ; *Silver/toxicity ; *Titanium/toxicity ; Transcriptome ; *Gastrointestinal Microbiome ; *Metal Nanoparticles/toxicity ; }, abstract = {Silver (nAg) and titanium dioxide (nTiO2) nanoparticles improve texture, flavour or anti-microbial properties of various food products and packaging materials. Despite their increased oral exposure, their potential toxicities in the dysfunctional intestine are unclear. Here, the effects of ingested nAg or nTiO2 on inflamed colon were revealed in a mouse model of chemical-induced acute ulcerative colitis. Mice (eight/group) were exposed to nAg or nTiO2 by oral gavage for 10 consecutive days. We characterized disease phenotypes, histology, and alterations in colonic transcriptome (RNA sequencing) and gut microbiome (16S sequencing). Oral exposure to nAg caused only minor changes in phenotypic hallmarks of colitic mice but induced extensive responses in gene expression enriching processes of apoptotic cell death and RNA metabolism. Instead, ingested nTiO2 yielded shorter colon, aggravated epithelial hyperplasia and deeper infiltration of inflammatory cells. Both nanoparticles significantly changed the gut microbiota composition, resulting in loss of diversity and increase of potential pathobionts. They also increased colonic mucus and abundance of Akkermansia muciniphila. Overall, nAg and nTiO2 induce dissimilar immunotoxicological changes at the molecular and microbiome level in the context of colon inflammation. The results provide valuable information for evaluation of utilizing metallic nanoparticles in food products for the vulnerable population.}, }
@article {pmid36084152, year = {2022}, author = {Pinto, S and Benincà, E and van Nes, EH and Scheffer, M and Bogaards, JA}, title = {Species abundance correlations carry limited information about microbial network interactions.}, journal = {PLoS computational biology}, volume = {18}, number = {9}, pages = {e1010491}, pmid = {36084152}, issn = {1553-7358}, mesh = {Bacteria ; Cross-Sectional Studies ; Humans ; *Microbial Interactions ; *Microbiota ; Phylogeny ; }, abstract = {Unraveling the network of interactions in ecological communities is a daunting task. Common methods to infer interspecific interactions from cross-sectional data are based on co-occurrence measures. For instance, interactions in the human microbiome are often inferred from correlations between the abundances of bacterial phylogenetic groups across subjects. We tested whether such correlation-based methods are indeed reliable for inferring interaction networks. For this purpose, we simulated bacterial communities by means of the generalized Lotka-Volterra model, with variation in model parameters representing variability among hosts. Our results show that correlations can be indicative for presence of bacterial interactions, but only when measurement noise is low relative to the variation in interaction strengths between hosts. Indication of interaction was affected by type of interaction network, process noise and sampling under non-equilibrium conditions. The sign of a correlation mostly coincided with the nature of the strongest pairwise interaction, but this is not necessarily the case. For instance, under rare conditions of identical interaction strength, we found that competitive and exploitative interactions can result in positive as well as negative correlations. Thus, cross-sectional abundance data carry limited information on specific interaction types. Correlations in abundance may hint at interactions but require independent validation.}, }
@article {pmid36078075, year = {2022}, author = {Bachmann, R and Van Hul, M and Baldin, P and Léonard, D and Delzenne, NM and Belzer, C and Ouwerkerk, JP and Repsilber, D and Rangel, I and Kartheuser, A and Brummer, RJ and De Vos, WM and Cani, PD}, title = {Akkermansia muciniphila Reduces Peritonitis and Improves Intestinal Tissue Wound Healing after a Colonic Transmural Defect by a MyD88-Dependent Mechanism.}, journal = {Cells}, volume = {11}, number = {17}, pages = {}, pmid = {36078075}, issn = {2073-4409}, mesh = {*Akkermansia ; Animals ; Colon/microbiology/pathology ; Humans ; Mice ; *Myeloid Differentiation Factor 88/metabolism ; *Peritonitis/metabolism/therapy ; Pilot Projects ; Verrucomicrobia/metabolism ; *Wound Healing/genetics/physiology ; }, abstract = {Anastomotic leakage is a major complication following colorectal surgery leading to peritonitis, complications, and mortality. Akkermansia muciniphila has shown beneficial effects on the gut barrier function. Whether A. muciniphila reduces peritonitis and mortality during colonic leakage is unknown. Whether A. muciniphila can directly modulate the expression of genes in the colonic mucosa in humans has never been studied. We investigated the effects of a pretreatment (14 days) with live A. muciniphila prior to surgical colonic perforation on peritonitis, mortality, and wound healing. We used mice with an inducible intestinal-epithelial-cell-specific deletion of MyD88 (IEC-MyD88 KO) to investigate the role of the innate immune system in this context. In a proof-of-concept pilot study, healthy humans were exposed to A. muciniphila for 2 h and colonic biopsies taken before and after colonic instillation for transcriptomic analysis. Seven days after colonic perforation, A.-muciniphila-treated mice had significantly lower mortality and severity of peritonitis. This effect was associated with significant improvements of wound histological healing scores, higher production of IL22, but no changes in the mucus layer thickness or genes involved in cell renewal, proliferation, or differentiation. All these effects were abolished in IEC-MyD88 KO mice. Finally, human subjects exposed to A. muciniphila exhibited an increased level of the bacterium at the mucus level 2 h after instillation and significant changes in the expression of different genes involved in the regulation of cell cycling, gene transcription, immunity, and inflammation in their colonic mucosa. A. muciniphila improves wound healing during transmural colonic wall defect through mechanisms possibly involving IL22 signaling and requiring MyD88 in the intestinal cells. In healthy humans, colonic administration of A. muciniphila is well tolerated and changes the expression of genes involved in the immune pathways.}, }
@article {pmid36073919, year = {2022}, author = {Wang, YR and Zhu, T and Kong, FQ and Duan, YY and Galzote, C and Quan, ZX}, title = {Infant Mode of Delivery Shapes the Skin Mycobiome of Prepubescent Children.}, journal = {Microbiology spectrum}, volume = {10}, number = {5}, pages = {e0226722}, pmid = {36073919}, issn = {2165-0497}, mesh = {Infant ; Infant, Newborn ; Child ; Female ; Pregnancy ; Humans ; Aged ; *Mycobiome ; *Microbiota ; Skin/microbiology ; Candida ; Fungi/genetics ; }, abstract = {Characterizing the skin mycobiome is necessary to define its association with the host immune system, particularly in children. In this study, we describe the skin mycobiome on the face, ventral forearm, and calf of 72 prepubescent children (aged 1 to 10 years) and their mothers, based on internal transcribed spacer (ITS) amplicon sequencing. The age and delivery mode at birth are the most influential factors shaping the skin mycobiome. Compared with that of the vaginally born children, the skin mycobiome of caesarean-born children is assembled by predominantly deterministic niche-based processes and exhibits a more fragile microbial network at all three sampling sites. Moreover, vaginal delivery leads to clearer intra- and interindividual specialization of fungal structures with increasing age; this phenomenon is not observed in caesarean-born children. The maternal correlation with children also differs based on the mode of delivery; specifically, the mycobiomes of vaginally born children at younger ages are more strongly correlated with vagina-associated fungal genera (Candida and Rhodotorula), whereas those of caesarean-delivered children at elder age include more skin-associated and airborne fungal genera (Malassezia and Alternaria). Based on this ecological framework, our results suggest that the delivery mode is significantly associated with maturation of the skin fungal community in children. IMPORTANCE Human skin is permanently colonized by microbes starting at birth. The hygiene hypothesis suggests that a lack of early-life immune imprinting weakens the body's resilience against atopic disorders later in life. To better understand fungal colonization following early-life periods affected by interruption, we studied the skin mycobiomes of 73 children and their mothers. Our results suggest a differentiation of the skin mycobiomes between caesarean-born and vaginally born children. Caesarean-born children exhibit a mycobiome structure with more fitted deterministic niche-based processes, a fragile network, and an unchanged microbial dissimilarity over time. In vaginally born children, this dissimilarity increases with age. The results indicate that initial microbial colonization has a long-term impact on a child's skin mycobiome. We believe that these findings will inspire further investigations of the "hygiene hypothesis" in the human microbiome, especially in providing novel insights into influences on the development of the early-life microbiome.}, }
@article {pmid36071979, year = {2022}, author = {Piazzesi, A and Putignani, L}, title = {Extremely small and incredibly close: Gut microbes as modulators of inflammation and targets for therapeutic intervention.}, journal = {Frontiers in microbiology}, volume = {13}, number = {}, pages = {958346}, pmid = {36071979}, issn = {1664-302X}, abstract = {Chronic inflammation is a hallmark for a variety of disorders and is at least partially responsible for disease progression and poor patient health. In recent years, the microbiota inhabiting the human gut has been associated with not only intestinal inflammatory diseases but also those that affect the brain, liver, lungs, and joints. Despite a strong correlation between specific microbial signatures and inflammation, whether or not these microbes are disease markers or disease drivers is still a matter of debate. In this review, we discuss what is known about the molecular mechanisms by which the gut microbiota can modulate inflammation, both in the intestine and beyond. We identify the current gaps in our knowledge of biological mechanisms, discuss how these gaps have likely contributed to the uncertain outcome of fecal microbiota transplantation and probiotic clinical trials, and suggest how both mechanistic insight and -omics-based approaches can better inform study design and therapeutic intervention.}, }
@article {pmid36069455, year = {2022}, author = {Maringanti, VS and Bucci, V and Gerber, GK}, title = {MDITRE: Scalable and Interpretable Machine Learning for Predicting Host Status from Temporal Microbiome Dynamics.}, journal = {mSystems}, volume = {7}, number = {5}, pages = {e0013222}, pmid = {36069455}, issn = {2379-5077}, support = {R01 GM130777/GM/NIGMS NIH HHS/United States ; 1R01GM130777//HHS | NIH | National Institute of General Medical Sciences (NIGMS)/ ; }, mesh = {Humans ; RNA, Ribosomal, 16S/genetics ; *Microbiota/genetics ; Machine Learning ; Software ; Metagenomics/methods ; }, abstract = {Longitudinal microbiome data sets are being generated with increasing regularity, and there is broad recognition that these studies are critical for unlocking the mechanisms through which the microbiome impacts human health and disease. However, there is a dearth of computational tools for analyzing microbiome time-series data. To address this gap, we developed an open-source software package, Microbiome Differentiable Interpretable Temporal Rule Engine (MDITRE), which implements a new highly efficient method leveraging deep-learning technologies to derive human-interpretable rules that predict host status from longitudinal microbiome data. Using semi-synthetic and a large compendium of publicly available 16S rRNA amplicon and metagenomics sequencing data sets, we demonstrate that in almost all cases, MDITRE performs on par with or better than popular uninterpretable machine learning methods, and orders-of-magnitude faster than the prior interpretable technique. MDITRE also provides a graphical user interface, which we show through case studies can be used to derive biologically meaningful interpretations linking patterns of microbiome changes over time with host phenotypes. IMPORTANCE The human microbiome, or collection of microbes living on and within us, changes over time. Linking these changes to the status of the human host is crucial to understanding how the microbiome influences a variety of human diseases. Due to the large scale and complexity of microbiome data, computational methods are essential. Existing computational methods for linking changes in the microbiome to the status of the human host are either unable to scale to large and complex microbiome data sets or cannot produce human-interpretable outputs. We present a new computational method and software package that overcomes the limitations of previous methods, allowing researchers to analyze larger and more complex data sets while producing easily interpretable outputs. Our method has the potential to enable new insights into how changes in the microbiome over time maintain health or lead to disease in humans and facilitate the development of diagnostic tests based on the microbiome.}, }
@article {pmid36068280, year = {2022}, author = {Kaiyrlykyzy, A and Kozhakhmetov, S and Babenko, D and Zholdasbekova, G and Alzhanova, D and Olzhayev, F and Baibulatova, A and Kushugulova, AR and Askarova, S}, title = {Study of gut microbiota alterations in Alzheimer's dementia patients from Kazakhstan.}, journal = {Scientific reports}, volume = {12}, number = {1}, pages = {15115}, pmid = {36068280}, issn = {2045-2322}, mesh = {Aged ; *Alzheimer Disease ; Bacteria/genetics ; Bacteroides/genetics ; Faecalibacterium/genetics ; Feces/microbiology ; *Gastrointestinal Microbiome/genetics ; Humans ; Kazakhstan ; *Microbiota ; RNA, Ribosomal, 16S/genetics ; }, abstract = {We have investigated the diversity and composition of gut microbiotas isolated from AD (Alzheimer's disease) patients (n = 41) and healthy seniors (n = 43) from Nur-Sultan city (Kazakhstan). The composition of the gut microbiota was characterized by 16S ribosomal RNA sequencing. Our results demonstrated significant differences in bacterial abundance at phylum, class, order, and genus levels in AD patients compared to healthy aged individuals. Relative abundance analysis has revealed increased amount of taxa belonging to Acidobacteriota, Verrucomicrobiota, Planctomycetota and Synergistota phyla in AD patients. Among bacterial genera, microbiotas of AD participants were characterized by a decreased amount of Bifidobacterium, Clostridia bacterium, Castellaniella, Erysipelotrichaceae UCG-003, Roseburia, Tuzzerella, Lactobacillaceae and Monoglobus. Differential abundance analysis determined enriched genera of Christensenellaceae R-7 group, Prevotella, Alloprevotella, Eubacterium coprostanoligenes group, Ruminococcus, Flavobacterium, Ohtaekwangia, Akkermansia, Bacteroides sp. Marseille-P3166 in AD patients, whereas Levilactobacillus, Lactiplantibacillus, Tyzzerella, Eubacterium siraeum group, Monoglobus, Bacteroides, Erysipelotrichaceae UCG-003, Veillonella, Faecalibacterium, Roseburia, Haemophilus were depleted. We have also found correlations between some bacteria taxa and blood serum biochemical parameters. Adiponectin was correlated with Acidimicrobiia, Faecalibacterium, Actinobacteria, Oscillospiraceae, Prevotella and Christensenellaceae R-7. The Christensenellaceae R-7 group and Acidobacteriota were correlated with total bilirubin, while Firmicutes, Acidobacteriales bacterium, Castellaniella alcaligenes, Lachnospiraceae, Christensenellaceae and Klebsiella pneumoniae were correlated with the level of CRP in the blood of AD patients. In addition, we report the correlations found between disease severity and certain fecal bacteria. This is the first reported study demonstrating gut microbiota alterations in AD in the Central Asian region.}, }
@article {pmid36068270, year = {2022}, author = {Ke, S and Weiss, ST and Liu, YY}, title = {Dissecting the role of the human microbiome in COVID-19 via metagenome-assembled genomes.}, journal = {Nature communications}, volume = {13}, number = {1}, pages = {5235}, pmid = {36068270}, issn = {2041-1723}, support = {U19 AI095219/AI/NIAID NIH HHS/United States ; U01 HL089856/HL/NHLBI NIH HHS/United States ; RF1 AG067744/AG/NIA NIH HHS/United States ; R01 AI141529/AI/NIAID NIH HHS/United States ; R01 HD093761/HD/NICHD NIH HHS/United States ; UH3 OD023268/OD/NIH HHS/United States ; }, mesh = {*COVID-19 ; *Gastrointestinal Microbiome/genetics ; Humans ; Metagenome/genetics ; *Microbiota ; SARS-CoV-2/genetics ; }, abstract = {Coronavirus disease 2019 (COVID-19), primarily a respiratory disease caused by infection with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), is often accompanied by gastrointestinal symptoms. However, little is known about the relation between the human microbiome and COVID-19, largely due to the fact that most previous studies fail to provide high taxonomic resolution to identify microbes that likely interact with SARS-CoV-2 infection. Here we used whole-metagenome shotgun sequencing data together with assembly and binning strategies to reconstruct metagenome-assembled genomes (MAGs) from 514 COVID-19 related nasopharyngeal and fecal samples in six independent cohorts. We reconstructed a total of 11,584 medium-and high-quality microbial MAGs and obtained 5403 non-redundant MAGs (nrMAGs) with strain-level resolution. We found that there is a significant reduction of strain richness for many species in the gut microbiome of COVID-19 patients. The gut microbiome signatures can accurately distinguish COVID-19 cases from healthy controls and predict the progression of COVID-19. Moreover, we identified a set of nrMAGs with a putative causal role in the clinical manifestations of COVID-19 and revealed their functional pathways that potentially interact with SARS-CoV-2 infection. Finally, we demonstrated that the main findings of our study can be largely validated in three independent cohorts. The presented results highlight the importance of incorporating the human gut microbiome in our understanding of SARS-CoV-2 infection and disease progression.}, }
@article {pmid36063358, year = {2023}, author = {Piazzesi, A and Putignani, L}, title = {Impact of helminth-microbiome interactions on childhood health and development-A clinical perspective.}, journal = {Parasite immunology}, volume = {45}, number = {4}, pages = {e12949}, doi = {10.1111/pim.12949}, pmid = {36063358}, issn = {1365-3024}, mesh = {Animals ; Child ; Humans ; *Helminths ; *Microbiota ; *Gastrointestinal Microbiome ; }, abstract = {Humans have co-existed with parasites for virtually the entirety of our existence as a species. Today, nearly one third of the human population is infected with at least one helminthic species, most of which reside in the intestinal tract, where they have co-evolved alongside the human gut microbiota (GM). Appreciation for the interconnected relationship between helminths and GM has increased in recent years. Here, we review the evidence of how helminths and GM can influence various aspects of childhood development and the onset of paediatric diseases. We discuss the emerging evidence of how many of the changes that parasitic worms inflict on their host is enacted through gut microbes. In this light, we argue that helminth-induced microbiota modifications are of great importance in both facing the global challenge of overcoming parasitic infections, and in replicating helminthic protective effects against inflammatory diseases. We propose that deepening our knowledge of helminth-microbiota interactions will uncover novel, safer and more effective therapeutic strategies in combatting an array of childhood disorders.}, }
@article {pmid36059540, year = {2022}, author = {Puhlmann, ML and de Vos, WM}, title = {Intrinsic dietary fibers and the gut microbiome: Rediscovering the benefits of the plant cell matrix for human health.}, journal = {Frontiers in immunology}, volume = {13}, number = {}, pages = {954845}, pmid = {36059540}, issn = {1664-3224}, mesh = {Dietary Fiber/metabolism ; *Gastrointestinal Microbiome ; Gastrointestinal Tract/metabolism ; Humans ; Plant Cells/metabolism ; Plants/metabolism ; }, abstract = {Dietary fibers contribute to structure and storage reserves of plant foods and fundamentally impact human health, partly by involving the intestinal microbiota, notably in the colon. Considerable attention has been given to unraveling the interaction between fiber type and gut microbiota utilization, focusing mainly on single, purified fibers. Studying these fibers in isolation might give us insights into specific fiber effects, but neglects how dietary fibers are consumed daily and impact our digestive tract: as intrinsic structures that include the cell matrix and content of plant tissues. Like our ancestors we consume fibers that are entangled in a complex network of plants cell walls that further encapsulate and shield intra-cellular fibers, such as fructans and other components from immediate breakdown. Hence, the physiological behavior and consequent microbial breakdown of these intrinsic fibers differs from that of single, purified fibers, potentially entailing unexplored health effects. In this mini-review we explain the difference between intrinsic and isolated fibers and discuss their differential impact on digestion. Subsequently, we elaborate on how food processing influences intrinsic fiber structure and summarize available human intervention studies that used intrinsic fibers to assess gut microbiota modulation and related health outcomes. Finally, we explore current research gaps and consequences of the intrinsic plant tissue structure for future research. We postulate that instead of further processing our already (extensively) processed foods to create new products, we should minimize this processing and exploit the intrinsic health benefits that are associated with the original cell matrix of plant tissues.}, }
@article {pmid36053959, year = {2022}, author = {Pepe, J and Rossi, M and Battafarano, G and Vernocchi, P and Conte, F and Marzano, V and Mariani, E and Mortera, SL and Cipriani, C and Rana, I and Buonuomo, PS and Bartuli, A and De Martino, V and Pelle, S and Pascucci, L and Toniolo, RM and Putignani, L and Minisola, S and Del Fattore, A}, title = {Characterization of Extracellular Vesicles in Osteoporotic Patients Compared to Osteopenic and Healthy Controls.}, journal = {Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research}, volume = {37}, number = {11}, pages = {2186-2200}, pmid = {36053959}, issn = {1523-4681}, mesh = {Humans ; Female ; Leukocytes, Mononuclear/metabolism ; Proteomics ; *Extracellular Vesicles/metabolism ; *MicroRNAs/genetics/metabolism ; Biomarkers/metabolism ; }, abstract = {Extracellular vesicles (EVs) are mediators of a range of pathological conditions. However, their role in bone loss disease has not been well understood. In this study we characterized plasma EVs of 54 osteoporotic (OP) postmenopausal women compared to 48 osteopenic (OPN) and 44 healthy controls (CN), and we investigated their effects on osteoclasts and osteoblasts. We found no differences between the three groups in terms of anthropometric measurements and biochemical evaluation of serum calcium, phosphate, creatinine, PTH, 25-hydroxy vitamin D and bone biomarkers, except for an increase of CTX level in OP group. FACS analysis revealed that OP patients presented a significantly increased number of EVs and RANKL[+] EVs compared with both CN and OPN subjects. Total EVs are negatively associated with the lumbar spine T-score and femoral neck T-score. Only in the OPN patients we observed a positive association between the total number of EVs and RANKL[+] EVs with the serum RANKL. In vitro studies revealed that OP EVs supported osteoclastogenesis of healthy donor peripheral blood mononuclear cells at the same level observed following RANKL and M-CSF treatment, reduced the ability of mesenchymal stem cells to differentiate into osteoblasts, while inducing an increase of OSTERIX and RANKL expression in mature osteoblasts. The analysis of miRNome revealed that miR-1246 and miR-1224-5p were the most upregulated and downregulated in OP EVs; the modulated EV-miRNAs in OP and OPN compared to CN are related to osteoclast differentiation, interleukin-13 production and regulation of canonical WNT pathway. A proteomic comparison between OPN and CN EVs evidenced a decrease in fibrinogen, vitronectin, and clusterin and an increase in coagulation factors and apolipoprotein, which was also upregulated in OP EVs. Interestingly, an increase in RANKL[+] EVs and exosomal miR-1246 was also observed in samples from patients affected by Gorham-Stout disease, suggesting that EVs could be good candidate as bone loss disease biomarkers. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).}, }
@article {pmid36053301, year = {2022}, author = {Frost, F}, title = {[Introduction to the microbiome].}, journal = {Innere Medizin (Heidelberg, Germany)}, volume = {63}, number = {10}, pages = {1015-1021}, pmid = {36053301}, issn = {2731-7099}, mesh = {Bacteria ; Dysbiosis ; *Gastrointestinal Microbiome ; Humans ; *Microbiota ; Obesity/therapy ; }, abstract = {The human body is colonized by a multitude of different microbes that are collectively referred to as the human microbiome. Gut microbes account for the largest proportion of these. They constitute a barrier against foreign pathogens, carry out important metabolic functions and regulate the immune system, thereby making them essential for the maintenance of health. The most important determinants of the gut microbiome structure in the general population include exocrine pancreatic function, genetics, nutrition, age, sex, and obesity. Changes in the gut microbiome have also been linked to a variety of diseases not limited to gastrointestinal disorders. Typical microbiome changes in disease include a loss of diversity and beneficial bacteria or an increase in opportunistic pathogens. This may result in a proinflammatory and unstable microbiome. Knowledge about the microbiome is rapidly increasing and microbiome modulation therapies have already been implemented in clinical practice. Therefore, basic knowledge about the microbiome is essential for all medical professionals in order for them to advise and treat their patients properly.}, }
@article {pmid36051769, year = {2022}, author = {Yu, Y and Wen, H and Li, S and Cao, H and Li, X and Ma, Z and She, X and Zhou, L and Huang, S}, title = {Emerging microfluidic technologies for microbiome research.}, journal = {Frontiers in microbiology}, volume = {13}, number = {}, pages = {906979}, pmid = {36051769}, issn = {1664-302X}, abstract = {The importance of the microbiome is increasingly prominent. For example, the human microbiome has been proven to be strongly associated with health conditions, while the environmental microbiome is recognized to have a profound influence on agriculture and even the global climate. Furthermore, the microbiome can serve as a fascinating reservoir of genes that encode tremendously valuable compounds for industrial and medical applications. In the past decades, various technologies have been developed to better understand and exploit the microbiome. In particular, microfluidics has demonstrated its strength and prominence in the microbiome research. By taking advantage of microfluidic technologies, inherited shortcomings of traditional methods such as low throughput, labor-consuming, and high-cost are being compensated or bypassed. In this review, we will summarize a broad spectrum of microfluidic technologies that have addressed various needs in the field of microbiome research, as well as the achievements that were enabled by the microfluidics (or technological advances). Finally, how microfluidics overcomes the limitations of conventional methods by technology integration will also be discussed.}, }
@article {pmid36050385, year = {2022}, author = {Hoegenauer, C and Hammer, HF and Mahnert, A and Moissl-Eichinger, C}, title = {Methanogenic archaea in the human gastrointestinal tract.}, journal = {Nature reviews. Gastroenterology &amp; hepatology}, volume = {19}, number = {12}, pages = {805-813}, pmid = {36050385}, issn = {1759-5053}, support = {P 32697/FWF_/Austrian Science Fund FWF/Austria ; }, mesh = {Humans ; *Archaea/physiology ; *Euryarchaeota ; Gastrointestinal Tract/microbiology ; Methane ; Bacteria ; }, abstract = {The human microbiome is strongly interwoven with human health and disease. Besides bacteria, viruses and eukaryotes, numerous archaea are located in the human gastrointestinal tract and are responsible for methane production, which can be measured in clinical methane breath analyses. Methane is an important readout for various diseases, including intestinal methanogen overgrowth. Notably, the archaea responsible for methane production are largely overlooked in human microbiome studies due to their non-bacterial biology and resulting detection issues. As such, their importance for health and disease remains largely unclear to date, in particular as not a single archaeal representative has been deemed to be pathogenic. In this Perspective, we discuss the current knowledge on the clinical relevance of methanogenic archaea. We explain the archaeal unique response to antibiotics and their negative and positive effects on human physiology, and present the current understanding of the use of methane as a diagnostic marker.}, }
@article {pmid36048299, year = {2022}, author = {Yi, B and Chen, H}, title = {Power law analysis of the human milk microbiome.}, journal = {Archives of microbiology}, volume = {204}, number = {9}, pages = {585}, pmid = {36048299}, issn = {1432-072X}, support = {GREKF21-06//Key Laboratory of Microbial Resources and Drug Development in Guizhou Province/ ; 202001BA070001-100//Applied Basic Research Foundation of Yunnan Province/ ; A0604//National Science and Technology Planning Project/ ; 202101BA070001-018//Yunnan Province Local University (Part) Basic Research for Youths/ ; }, mesh = {Ecology ; Female ; Humans ; *Microbiota ; *Milk, Human ; Models, Biological ; }, abstract = {The human breast milk microbiome (HMM) has far reached health implications for both mothers and infants, and understanding the structure and dynamics of milk microbial communities is therefore of critical biomedical importance. Community heterogeneity, which has certain commonalities with familiar diversity but also with certain fundamental differences, is an important aspect of community structure and dynamics. Taylor's (1961) power law (TPL) (Nature, 1961) was discovered to govern the mean-variance power function relationship of population abundances and can be used to characterize population spatial aggregation (heterogeneity) and/or temporal stability. TPL was further extended to the community level to measure community spatial heterogeneity and/or temporal stability (Ma 2015, Molecular Ecology). Here, we applied TPL extensions (TPLE) to analyze the heterogeneity of the human milk microbiome by reanalyzing 12 datasets (2115 samples) of the healthy human milk microbiome. Our analysis revealed that the TPLE heterogeneity parameter (b) is rather stable across the 12 datasets, and there were approximately no statistically significant differences among ¾ of the datasets, which is consistent with the hypothesis that the heterogeneity scaling (i.e., change across individuals) of the human microbiome, including HMM, is rather stable or even constant. For this, we built a TPLE model for the pooled 12 datasets (b = 1.906), which can therefore represent the scaling rate of community-level spatial heterogeneity of HMM across individuals. Similarly, we also analyzed mixed-species ("averaged virtual species") level heterogeneity of HMM, and it was found that the mixed-species level heterogeneity was smaller than the heterogeneity at the previously mentioned community level (1.620 vs. 1.906).}, }
@article {pmid36047711, year = {2023}, author = {Stefanaki, E and Kalaitzidou, I and Aristou, M and Lakoumentas, J and Galanakis, E and Xepapadaki, P}, title = {Prenatal antibiotic exposure increases the risk of infant atopic dermatitis: data from a Greek cohort.}, journal = {European annals of allergy and clinical immunology}, volume = {55}, number = {6}, pages = {271-277}, doi = {10.23822/EurAnnACI.1764-1489.266}, pmid = {36047711}, issn = {1764-1489}, mesh = {Child ; Infant ; Humans ; Female ; Pregnancy ; Male ; *Dermatitis, Atopic/diagnosis/epidemiology ; Greece/epidemiology ; Anti-Bacterial Agents/adverse effects ; Cesarean Section/adverse effects ; *Prenatal Exposure Delayed Effects/epidemiology ; Risk Factors ; *Food Hypersensitivity/epidemiology ; }, abstract = {Background. The human microbiome is important due to the impact it has on host immunologic development and allergy-associated diseases. This study aimed to investigate the impact of prenatal exposure to antibiotics on the incidence of atopic dermatitis (AD) in children at 18 months of age. Methods. Mothers were interviewed at baseline, in the maternity ward and by phone questionnaire after 18 months. Demographic data, mode of delivery, yoghurt consumption, antibiotic and other drug use during pregnancy, atopic history, diagnosis of AD and history of infections in the offspring were noted. Results. 385 mothers were interviewed at baseline. 231 (60%) mothers with 236 children responded at follow up. Cesarean section was reported in 116 (50.2%) deliveries while antibiotic use during pregnancy in 55/231 (23.8%) women. 43/236 (18.22%) infants were diagnosed with AD. Intravenous antibiotic use was associated with a 7.7 increased risk of AD diagnosis in the offspring (95%CI 1.23-48.27, p = 0.029). An increased odd for AD was recorded for mothers 30-40 years of age (OR 4.50, 95%CI 1.08-18.7, p = 0.039). No significant association between cesarean section and AD (p = 0.70) was recorded. In multivariate analysis, reported food allergy (OR 8.03, 95%CI 2.30-27.97, p = 0.001) and otitis media episodes in children (OR 3.76, 95%CI 1.60-8.83, p = 0.002) were significantly associated with AD diagnosis. Conclusions. An increased risk of AD was recorded only when antibiotics were given prenatally by intravenous route and in women between 30-40 years of age. Children with food allergy had an increased risk for AD. The relatively high percentage of cesarean sections was not a risk factor for AD.}, }
@article {pmid36046741, year = {2022}, author = {Nie, F and Wang, L and Huang, Y and Yang, P and Gong, P and Feng, Q and Yang, C}, title = {Characteristics of Microbial Distribution in Different Oral Niches of Oral Squamous Cell Carcinoma.}, journal = {Frontiers in cellular and infection microbiology}, volume = {12}, number = {}, pages = {905653}, pmid = {36046741}, issn = {2235-2988}, mesh = {Bacteria/genetics ; *Carcinoma, Squamous Cell ; *Head and Neck Neoplasms ; Humans ; *Microbiota ; *Mouth Neoplasms/diagnosis ; Squamous Cell Carcinoma of Head and Neck ; }, abstract = {Oral squamous cell carcinoma (OSCC), one of the most common malignant tumors of the head and neck, is closely associated with the presence of oral microbes. However, the microbiomes of different oral niches in OSCC patients and their association with OSCC have not been adequately characterized. In this study, 305 samples were collected from 65 OSCC patients, including tumor tissue, adjacent normal tissue (paracancerous tissue), cancer surface tissue, anatomically matched contralateral normal mucosa, saliva, and tongue coat. 16S ribosomal DNA (16S rDNA) sequencing was used to compare the microbial composition, distribution, and co-occurrence network of different oral niches. The association between the microbiome and the clinical features of OSCC was also characterized. The oral microbiome of OSCC patients showed a regular ecological distribution. Tumor and paracancerous tissues were more microbially diverse than other oral niches. Cancer surface, contralateral normal mucosa, saliva, and tongue coat showed similar microbial compositions, especially the contralateral normal mucosa and saliva. Periodontitis-associated bacteria of the genera Fusobacterium, Prevotella, Porphyromonas, Campylobacter, and Aggregatibacter, and anaerobic bacteria were enriched in tumor samples. The microbiome was highly correlated with tumor clinicopathological features, with several genera (Lautropia, Asteroleplasma, Parvimonas, Peptostreptococcus, Pyramidobacter, Roseburia, and Propionibacterium) demonstrating a relatively high diagnostic power for OSCC metastasis, potentially providing an indicator for the development of OSCC.}, }
@article {pmid36040412, year = {2023}, author = {Höyhtyä, M and Korpela, K and Saqib, S and Junkkari, S and Nissilä, E and Nikkonen, A and Dikareva, E and Salonen, A and de Vos, WM and Kolho, KL}, title = {Quantitative Fecal Microbiota Profiles Relate to Therapy Response During Induction With Tumor Necrosis Factor α Antagonist Infliximab in Pediatric Inflammatory Bowel Disease.}, journal = {Inflammatory bowel diseases}, volume = {29}, number = {1}, pages = {116-124}, pmid = {36040412}, issn = {1536-4844}, mesh = {Humans ; Child ; Infliximab/therapeutic use ; Tumor Necrosis Factor-alpha ; Tumor Necrosis Factor Inhibitors ; *Inflammatory Bowel Diseases/drug therapy ; Feces/chemistry ; *Microbiota ; Leukocyte L1 Antigen Complex/analysis ; }, abstract = {BACKGROUND: The role of intestinal microbiota in inflammatory bowel diseases is intensively researched. Pediatric studies on the relation between microbiota and treatment response are sparse. We aimed to determine whether absolute abundances of gut microbes characterize the response to infliximab induction in pediatric inflammatory bowel disease.<br><br>METHODS: We recruited pediatric patients with inflammatory bowel disease introduced to infliximab at Children's Hospital, University of Helsinki. Stool samples were collected at 0, 2, and 6 weeks for microbiota and calprotectin analyses. We defined treatment response as fecal calprotectin value <100 &#xb5;g/g at week 6. Intestinal microbiota were analyzed by 16S ribosomal RNA gene amplicon sequencing using the Illumina MiSeq platform. We analyzed total bacterial counts using quantitative polymerase chain reaction and transformed the relative abundances into absolute abundances based on the total counts.<br><br>RESULTS: At baseline, the intestinal microbiota in the treatment responsive group (n&#x2005;=&#x2005;10) showed a higher absolute abundance of Bifidobacteriales and a lower absolute abundance of Actinomycetales than nonresponders (n&#x2005;=&#x2005;19). The level of inflammation according to fecal calprotectin showed no statistically significant association with the absolute abundances of fecal microbiota. The results on relative abundances differed from the absolute abundances. At the genus level, the responders had an increased relative abundance of Anaerosporobacter but a reduced relative abundance of Parasutterella at baseline.<br><br>CONCLUSIONS: High absolute abundance of Bifidobacteriales in the gut microbiota of pediatric patients reflects anti-inflammatory characteristics associated with rapid response to therapy. This warrants further studies on whether modification of pretreatment microbiota might improve the outcomes.}, }
@article {pmid36037921, year = {2022}, author = {Nava, AR and Daneshian, L and Sarma, H}, title = {Antibiotic resistant genes in the environment-exploring surveillance methods and sustainable remediation strategies of antibiotics and ARGs.}, journal = {Environmental research}, volume = {215}, number = {Pt 1}, pages = {114212}, doi = {10.1016/j.envres.2022.114212}, pmid = {36037921}, issn = {1096-0953}, mesh = {Animals ; *Anti-Bacterial Agents/pharmacology ; Bacteria/genetics ; Genes, Bacterial ; Humans ; Wastewater/analysis ; *Water Pollutants, Chemical ; }, abstract = {Antibiotic Resistant Genes (ARGs) are an emerging environmental health threat due to the potential change in the human microbiome and selection for the emergence of antibiotic resistant bacteria. The rise of antibiotic resistant bacteria has caused a global health burden. The WHO (world health organization) predicts a rise in deaths due to antibiotic resistant infections. Since bacteria can acquire ARGs through horizontal transmission, it is important to assess the dissemination of antibioticresistant genes from anthropogenic sources. There are several sources of antibiotics, antibiotic resistant bacteria and genes in the environment. These include wastewater treatment plants, landfill leachate, agricultural, animal industrial sources and estuaries. The use of antibiotics is a worldwide practice that has resulted in the evolution of resistance to antibiotics. Our review provides a more comprehensive look into multiple sources of ARG's and antibiotics rather than one. Moreover, we focus on effective surveillance methods of ARGs and antibiotics and sustainable abiotic and biotic remediation strategies for removal and reduction of antibiotics and ARGs from both terrestrial and aquatic environments. Further, we consider the impact on public health as this problem cannot be addressed without a global transdisciplinary effort.}, }
@article {pmid36014818, year = {2022}, author = {Lane, MM and Lotfaliany, M and Forbes, M and Loughman, A and Rocks, T and O'Neil, A and Machado, P and Jacka, FN and Hodge, A and Marx, W}, title = {Higher Ultra-Processed Food Consumption Is Associated with Greater High-Sensitivity C-Reactive Protein Concentration in Adults: Cross-Sectional Results from the Melbourne Collaborative Cohort Study.}, journal = {Nutrients}, volume = {14}, number = {16}, pages = {}, pmid = {36014818}, issn = {2072-6643}, mesh = {Adult ; *C-Reactive Protein/analysis ; Cohort Studies ; Cross-Sectional Studies ; Diet ; *Energy Intake ; Fast Foods/adverse effects/analysis ; Food Handling ; Humans ; }, abstract = {Background: Few studies have examined associations between ultra-processed food intake and biomarkers of inflammation, and inconsistent results have been reported in the small number of studies that do exist. As such, further investigation is required. Methods: Cross-sectional baseline data from the Melbourne Collaborative Cohort Study (MCCS) were analysed (n = 2018). We applied the NOVA food classification system to data from a food frequency questionnaire (FFQ) to determine ultra-processed food intake (g/day). The outcome was high-sensitivity C-reactive protein concentration (hsCRP; mg/L). We fitted unadjusted and adjusted linear regression analyses, with sociodemographic characteristics and lifestyle- and health-related behaviours as covariates. Supplementary analyses further adjusted for body mass index (kg/m2). Sex was assessed as a possible effect modifier. Ultra-processed food intake was modelled as 100 g increments and the magnitude of associations expressed as estimated relative change in hsCRP concentration with accompanying 95% confidence intervals (95%CIs). Results: After adjustment, every 100 g increase in ultra-processed food intake was associated with a 4.0% increase in hsCRP concentration (95%CIs: 2.1−5.9%, p < 0.001). Supplementary analyses showed that part of this association was independent of body mass index (estimated relative change in hsCRP: 2.5%; 95%CIs: 0.8−4.3%, p = 0.004). No interaction was observed between sex and ultra-processed food intake. Conclusion: Higher ultra-processed food intake was cross-sectionally associated with elevated hsCRP, which appeared to occur independent of body mass index. Future prospective and intervention studies are necessary to confirm directionality and whether the observed association is causal.}, }
@article {pmid36014376, year = {2022}, author = {Jo, H and Kim, SY and Kang, BH and Baek, C and Kwon, JE and Jeang, JW and Heo, YM and Kim, HB and Heo, CY and Kang, SM and Shin, BH and Nam, DY and Lee, YG and Kang, SC and Lee, DG}, title = {Staphylococcus epidermidis Cicaria, a Novel Strain Derived from the Human Microbiome, and Its Efficacy as a Treatment for Hair Loss.}, journal = {Molecules (Basel, Switzerland)}, volume = {27}, number = {16}, pages = {}, pmid = {36014376}, issn = {1420-3049}, mesh = {Adenosine ; Alopecia ; Biotin ; Hair Follicle ; Humans ; *Microbiota ; *Staphylococcus epidermidis ; }, abstract = {The skin tissue of the scalp is unique from other skin tissues because it coexists with hair, and many differences in microbial composition have been confirmed. In scalp tissues, hair loss occurs due to a combination of internal and external factors, and several studies are being conducted to counteract this. However, not many studies have addressed hair loss from the perspective of the microbiome. In this study, subjects with hair loss and those with normal scalps were set as experimental and control groups, respectively. In the experimental group, hair loss had progressed, and there was a large difference in microbiome composition compared to the group with normal scalps. In particular, differences in Accumulibacter, Staphylococcus, and Corynebacterium were found. From Staphylococcus epidermidis Cicaria, two active components were isolated as a result of repeated column chromatography. Spectroscopic data led to the determination of chemical structures for adenosine and biotin. Fractions were obtained, and ex vivo tests were conducted using hair follicles derived from human scalp tissue. When the microbiome adenosine-treated group was compared to the control group, hair follicle length was increased, and hair root diameter was maintained during the experimental periods. In addition, the Cicaria culture medium and the microbial adenosine- and biotin-treated groups maintained the anagen phase, reducing progression to the catagen phase in the hair growth cycle. In conclusion, it was confirmed that the Cicaria culture medium and the microbial adenosine and biotin derived from the culture were effective in inhibiting hair loss.}, }
@article {pmid36014023, year = {2022}, author = {Ouwerkerk, JP and Tytgat, HLP and Elzinga, J and Koehorst, J and Van den Abbeele, P and Henrissat, B and Gueimonde, M and Cani, PD and Van de Wiele, T and Belzer, C and de Vos, WM}, title = {Comparative Genomics and Physiology of Akkermansia muciniphila Isolates from Human Intestine Reveal Specialized Mucosal Adaptation.}, journal = {Microorganisms}, volume = {10}, number = {8}, pages = {}, pmid = {36014023}, issn = {2076-2607}, support = {BOF12-GOA-008//Ghent University/ ; Advanced Grand 250172 - Microbes Inside/ERC_/European Research Council/International ; Spinoza Award Willem M. de Vos/NWO_/Dutch Research Council/Netherlands ; SIAM Gravity Grant 024.002.002/NWO_/Dutch Research Council/Netherlands ; FRFS-WELBIO: WELBIO-CR-2022A-02//Fund for Scientific Research/ ; }, abstract = {Akkermansia muciniphila is a champion of mucin degradation in the human gastrointestinal tract. Here, we report the isolation of six novel strains from healthy human donors and their genomic, proteomic and physiological characterization in comparison to the type-strains A. muciniphila MucT and A. glycaniphila PytT. Complete genome sequencing revealed that, despite their large genomic similarity (>97.6%), the novel isolates clustered into two distinct subspecies of A. muciniphila: Amuc1, which includes the type-strain MucT, and AmucU, a cluster of unassigned strains that have not yet been well characterized. CRISPR analysis showed all strains to be unique and confirmed that single healthy subjects can carry more than one A. muciniphila strain. Mucin degradation pathways were strongly conserved amongst all isolates, illustrating the exemplary niche adaptation of A. muciniphila to the mucin interface. This was confirmed by analysis of the predicted glycoside hydrolase profiles and supported by comparing the proteomes of A. muciniphila strain H2, belonging to the AmucU cluster, to MucT and A. glycaniphila PytT (including 610 and 727 proteins, respectively). While some intrinsic resistance was observed among the A. muciniphila straind, none of these seem to pose strain-specific risks in terms of their antibiotic resistance patterns nor a significant risk for the horizontal transfer of antibiotic resistance determinants, opening the way to apply the type-strain MucT or these new A. muciniphila strains as next generation beneficial microbes.}, }
@article {pmid36013941, year = {2022}, author = {Harel, N and Reshef, L and Biran, D and Brenner, S and Ron, EZ and Gophna, U}, title = {Effect of Solar Radiation on Skin Microbiome: Study of Two Populations.}, journal = {Microorganisms}, volume = {10}, number = {8}, pages = {}, pmid = {36013941}, issn = {2076-2607}, abstract = {Here, we examined the skin microbiome of two groups of healthy volunteers living on the Mediterranean coast with different exposures to sun radiation. One group, exposed to the sun in the summer, was compared with a group covered with clothing throughout the year. The seasonal effects on the skin microbiome of three body sites were determined before and after summer. Surprisingly, at the phyla level, there were no significant differences in microbiome diversity between the groups. Furthermore, within each group, there were no significant seasonal differences in high-abundance species at any of the sampling sites. These results suggest that the skin microbiome, developed over years, remains stable even after several months of exposure to summer weather, direct sunlight and humidity. However, in the group exposed to the sun during the summer months, there were significant differences in low-abundance species in sun-exposed areas of the skin (the inner and outer arm). These subtle changes in low-abundance species are interesting, and their effect on skin physiology should be studied further.}, }
@article {pmid36010611, year = {2022}, author = {Huwart, SJP and de Wouters d'Oplinter, A and Rastelli, M and Van Hul, M and de Vos, WM and Luquet, S and Cani, PD and Everard, A}, title = {Food Reward Alterations during Obesity Are Associated with Inflammation in the Striatum in Mice: Beneficial Effects of Akkermansia muciniphila.}, journal = {Cells}, volume = {11}, number = {16}, pages = {}, pmid = {36010611}, issn = {2073-4409}, mesh = {Akkermansia ; Animals ; Inflammation/metabolism ; Male ; Mice ; Mice, Obese ; *Obesity/metabolism ; Reward ; *Verrucomicrobia/metabolism ; }, abstract = {The reward system involved in hedonic food intake presents neuronal and behavioral dysregulations during obesity. Moreover, gut microbiota dysbiosis during obesity promotes low-grade inflammation in peripheral organs and in the brain contributing to metabolic alterations. The mechanisms underlying reward dysregulations during obesity remain unclear. We investigated if inflammation affects the striatum during obesity using a cohort of control-fed or diet-induced obese (DIO) male mice. We tested the potential effects of specific gut bacteria on the reward system during obesity by administrating Akkermansia muciniphila daily or a placebo to DIO male mice. We showed that dysregulations of the food reward are associated with inflammation and alterations in the blood-brain barrier in the striatum of obese mice. We identified Akkermansia muciniphila as a novel actor able to improve the dysregulated reward behaviors associated with obesity, potentially through a decreased activation of inflammatory pathways and lipid-sensing ability in the striatum. These results open a new field of research and suggest that gut microbes can be considered as an innovative therapeutic approach to attenuate reward alterations in obesity. This study provides substance for further investigations of Akkermansia muciniphila-mediated behavioral improvements in other inflammatory neuropsychiatric disorders.}, }
@article {pmid36010298, year = {2022}, author = {Günther, V and Allahqoli, L and Watrowski, R and Maass, N and Ackermann, J and von Otte, S and Alkatout, I}, title = {Vaginal Microbiome in Reproductive Medicine.}, journal = {Diagnostics (Basel, Switzerland)}, volume = {12}, number = {8}, pages = {}, pmid = {36010298}, issn = {2075-4418}, abstract = {The human microbiome has been given increasing importance in recent years. The establishment of sequencing-based technology has made it possible to identify a large number of bacterial species that were previously beyond the scope of culture-based technologies. Just as microbiome diagnostics has emerged as a major point of focus in science, reproductive medicine has developed into a subject of avid interest, particularly with regard to causal research and treatment options for implantation failure. Thus, the vaginal microbiome is discussed as a factor influencing infertility and a promising target for treatment options. The present review provides an overview of current research concerning the impact of the vaginal microbiome on the outcome of reproductive measures. A non-Lactobacillus-dominated microbiome was shown to be associated with dysbiosis, possibly even bacterial vaginosis. This imbalance has a negative impact on implantation rates in assisted reproductive technologies and may also be responsible for habitual abortions. Screening of the microbiome in conjunction with antibiotic and/or probiotic treatment appears to be one way of improving pregnancy outcomes.}, }
@article {pmid36003766, year = {2022}, author = {Liang, J and Li, T and Zhao, J and Wang, C and Sun, H}, title = {Current understanding of the human microbiome in glioma.}, journal = {Frontiers in oncology}, volume = {12}, number = {}, pages = {781741}, pmid = {36003766}, issn = {2234-943X}, abstract = {There is mounting evidence that the human microbiome is highly associated with a wide variety of central nervous system diseases. However, the link between the human microbiome and glioma is rarely noticed. The exact mechanism of microbiota to affect glioma remains unclear. Recent studies have demonstrated that the microbiome may affect the development, progress, and therapy of gliomas, including the direct impacts of the intratumoral microbiome and its metabolites, and the indirect effects of the gut microbiome and its metabolites. Glioma-related microbiome (gut microbiome and intratumoral microbiome) is associated with both tumor microenvironment and tumor immune microenvironment, which ultimately influence tumorigenesis, progression, and responses to treatment. In this review, we briefly summarize current knowledge regarding the role of the glioma-related microbiome, focusing on its gut microbiome fraction and a brief description of the intratumoral microbiome, and put forward the prospects in which microbiome can be applied in the future and some challenges still need to be solved.}, }
@article {pmid36001521, year = {2023}, author = {Shen, Y and Zhu, J and Deng, Z and Lu, W and Wang, H}, title = {EnsDeepDP: An Ensemble Deep Learning Approach for Disease Prediction Through Metagenomics.}, journal = {IEEE/ACM transactions on computational biology and bioinformatics}, volume = {20}, number = {2}, pages = {986-998}, doi = {10.1109/TCBB.2022.3201295}, pmid = {36001521}, issn = {1557-9964}, mesh = {Humans ; Metagenomics ; *Deep Learning ; Algorithms ; Machine Learning ; *Microbiota/genetics ; }, abstract = {A growing number of studies show that the human microbiome plays a vital role in human health and can be a crucial factor in predicting certain human diseases. However, microbiome data are often characterized by the limited samples and high-dimensional features, which pose a great challenge for machine learning methods. Therefore, this paper proposes a novel ensemble deep learning disease prediction method that combines unsupervised and supervised learning paradigms. First, unsupervised deep learning methods are used to learn the potential representation of the sample. Afterwards, the disease scoring strategy is developed based on the deep representations as the informative features for ensemble analysis. To ensure the optimal ensemble, a score selection mechanism is constructed, and performance boosting features are engaged with the original sample. Finally, the composite features are trained with gradient boosting classifier for health status decision. For case study, the ensemble deep learning flowchart has been demonstrated on six public datasets extracted from the human microbiome profiling. The results show that compared with the existing algorithms, our framework achieves better performance on disease prediction.}, }
@article {pmid35998206, year = {2022}, author = {Li, J and George Markowitz, RH and Brooks, AW and Mallott, EK and Leigh, BA and Olszewski, T and Zare, H and Bagheri, M and Smith, HM and Friese, KA and Habibi, I and Lawrence, WM and Rost, CL and Lédeczi, &#xc1; and Eeds, AM and Ferguson, JF and Silver, HJ and Bordenstein, SR}, title = {Individuality and ethnicity eclipse a short-term dietary intervention in shaping microbiomes and viromes.}, journal = {PLoS biology}, volume = {20}, number = {8}, pages = {e3001758}, pmid = {35998206}, issn = {1545-7885}, support = {P30 DK058404/DK/NIDDK NIH HHS/United States ; R01 DK117144/DK/NIDDK NIH HHS/United States ; T32 HG008341/HG/NHGRI NIH HHS/United States ; }, mesh = {Bacteria/genetics ; Ethnicity ; Feces ; Female ; *Gastrointestinal Microbiome/genetics ; Humans ; *Microbiota/genetics ; Virome ; }, abstract = {Many diseases linked with ethnic health disparities associate with changes in microbial communities in the United States, but the causes and persistence of ethnicity-associated microbiome variation are not understood. For instance, microbiome studies that strictly control for diet across ethnically diverse populations are lacking. Here, we performed multiomic profiling over a 9-day period that included a 4-day controlled vegetarian diet intervention in a defined geographic location across 36 healthy Black and White females of similar age, weight, habitual diets, and health status. We demonstrate that individuality and ethnicity account for roughly 70% to 88% and 2% to 10% of taxonomic variation, respectively, eclipsing the effects a short-term diet intervention in shaping gut and oral microbiomes and gut viromes. Persistent variation between ethnicities occurs for microbial and viral taxa and various metagenomic functions, including several gut KEGG orthologs, oral carbohydrate active enzyme categories, cluster of orthologous groups of proteins, and antibiotic-resistant gene categories. In contrast to the gut and oral microbiome data, the urine and plasma metabolites tend to decouple from ethnicity and more strongly associate with diet. These longitudinal, multiomic profiles paired with a dietary intervention illuminate previously unrecognized associations of ethnicity with metagenomic and viromic features across body sites and cohorts within a single geographic location, highlighting the importance of accounting for human microbiome variation in research, health determinants, and eventual therapies. Trial Registration: ClinicalTrials.gov ClinicalTrials.gov Identifier: NCT03314194.}, }
@article {pmid35997152, year = {2022}, author = {Titécat, M and Rousseaux, C and Dubuquoy, C and Foligné, B and Rahmouni, O and Mahieux, S and Desreumaux, P and Woolston, J and Sulakvelidze, A and Wannerberger, K and Neut, C}, title = {Safety and Efficacy of an AIEC-targeted Bacteriophage Cocktail in a Mice Colitis Model.}, journal = {Journal of Crohn's &amp; colitis}, volume = {16}, number = {10}, pages = {1617-1627}, doi = {10.1093/ecco-jcc/jjac064}, pmid = {35997152}, issn = {1876-4479}, support = {//Ferring/ ; }, mesh = {Animals ; Humans ; Mice ; Bacterial Adhesion ; *Bacteriophages ; *Colitis/pathology ; Disease Models, Animal ; Dysbiosis/complications ; Escherichia coli ; Escherichia coli Infections/complications/microbiology/pathology ; Intestinal Mucosa/pathology ; }, abstract = {BACKGROUND AND AIMS: Adherent invasive Escherichia coli [AIEC] are recovered with a high frequency from the gut mucosa of Crohn's disease patients and are believed to contribute to the dysbiosis and pathogenesis of this inflammatory bowel disease. In this context, bacteriophage therapy has been proposed for specifically targeting AIEC in the human gut with no deleterious impact on the commensal microbiota.<br><br>METHODS: The in vitro efficacy and specificity of a seven lytic phage cocktail [EcoActive&#x2122;] was assessed against [i] 210 clinical AIEC strains, and [ii] 43 non-E. coli strains belonging to the top 12 most common bacterial genera typically associated with a healthy human microbiome. These data were supported by in vivo safety and efficacy assays conducted on healthy and AIEC-colonized mice, respectively.<br><br>RESULTS: The EcoActive cocktail was effective in vitro against 95% of the AIEC strains and did not lyse any of the 43 non-E. coli commensal strains, in contrast to conventional antibiotics. Long-term administration of the EcoActive cocktail to healthy mice was safe and did not induce dysbiosis according to metagenomic data. Using a murine model of induced colitis of animals infected with the AIEC strain LF82, we found that a single administration of the cocktail failed to alleviate inflammatory symptoms, while mice receiving the cocktail twice a day for 15 days were protected from clinical and microscopical manifestations of inflammation.<br><br>CONCLUSIONS: Collectively, the data support the approach of AIEC-targeted phage therapy as safe and effective treatment for reducing AIEC levels in the gut of IBD patients.}, }
@article {pmid35996476, year = {2022}, author = {Clark, KA and Bushin, LB and Seyedsayamdost, MR}, title = {RaS-RiPPs in Streptococci and the Human Microbiome.}, journal = {ACS bio &amp; med chem Au}, volume = {2}, number = {4}, pages = {328-339}, pmid = {35996476}, issn = {2694-2437}, abstract = {Radical S-adenosylmethionine (RaS) enzymes have quickly advanced to one of the most abundant and versatile enzyme superfamilies known. Their chemistry is predicated upon reductive homolytic cleavage of a carbon-sulfur bond in cofactor S-adenosylmethionine forming an oxidizing carbon-based radical, which can initiate myriad radical transformations. An emerging role for RaS enzymes is their involvement in the biosynthesis of ribosomally synthesized and post-translationally modified peptides (RiPPs), a natural product family that has become known as RaS-RiPPs. These metabolites are especially prevalent in human and mammalian microbiomes because the complex chemistry of RaS enzymes gives rise to correspondingly complex natural products with minimal cellular energy and genomic fingerprint, a feature that is advantageous in microbes with small, host-adapted genomes in competitive environments. Herein, we review the discovery and characterization of RaS-RiPPs from the human microbiome with a focus on streptococcal bacteria. We discuss the varied chemical modifications that RaS enzymes introduce onto their peptide substrates and the diverse natural products that they give rise to. The majority of RaS-RiPPs remain to be discovered, providing an intriguing avenue for future investigations at the intersection of metalloenzymology, chemical ecology, and the human microbiome.}, }
@article {pmid35993728, year = {2022}, author = {Vander Haar, EL and Wu, G and Gyamfi-Bannerman, C and Thomas, C and Wapner, RJ and Reddy, UM and Zhao, L and Silver, RM and Goldenberg, RL and Han, YW}, title = {Microbial Analysis of Umbilical Cord Blood Reveals Novel Pathogens Associated with Stillbirth and Early Preterm Birth.}, journal = {mBio}, volume = {13}, number = {5}, pages = {e0203622}, pmid = {35993728}, issn = {2150-7511}, support = {R01 CA192111/CA/NCI NIH HHS/United States ; R01 DE029532/DE/NIDCR NIH HHS/United States ; }, mesh = {Humans ; Infant, Newborn ; Pregnancy ; Female ; *Stillbirth/epidemiology ; Fetal Blood ; RNA, Ribosomal, 16S/genetics ; *Premature Birth/epidemiology ; Gestational Age ; }, abstract = {Stillbirths account for half of all perinatal mortality, but the underlying cause of a significant portion of the cases remains unknown. We set out to test the potential role and extent of microbial infection in stillbirth through a case-control analysis of fetal cord blood collected from the multisite Stillbirth Collaborative Research Network. Cases (n = 60) were defined as stillbirths at >20 weeks of gestation, and controls (n = 176) were live births. The bacterial presence, abundance, and composition were analyzed by endpoint PCR of full-length 16S rRNA and the V4 amplicon sequence variants (ASVs). The results demonstrate that bacterial prevalence and abundance were both significantly increased in stillbirth, even after adjusting for maternal age, race, body mass index, number of pregnancies, gestational age, and multiple gestations. Composition of bacterial communities in the cord blood also differed significantly. Using a group of 25 ASVs differentially abundant between the two groups, a Random Forest classification model achieved an accuracy score of 0.76 differentiating stillbirth and live birth, with Group B Streptococcus as the most enriched species in stillbirth. Positive PCR was also significantly associated with early preterm birth. A group of oral anaerobes, including Actinomyces, Campylobacter, Fusobacterium, Peptostreptococcus, Porphyromonas, and Prevotella, were enriched in live early preterm birth, suggesting possible oral origin of infection. Our ASV-based microbiome analysis revealed specific candidate pathogens associated with infections in stillbirth and early preterm birth. The cord blood microbial signatures may be markers of adverse pregnancy outcomes. Our study will help identify possible mechanism of infection and improve our ability to prevent stillbirth and early preterm birth. IMPORTANCE Stillbirth accounts for half of all perinatal mortality, but the underlying cause of a substantial portion of all cases remains elusive. We examined the umbilical cord blood microbiome in stillbirths (n = 60) and live births (n = 176) and discovered that the bacterial prevalence and abundance were significantly higher in stillbirths than live births. The microbial compositions also differed significantly. Group B Streptococcus was the most prevalent species detected in stillbirth. In addition, pathogens previously unknown to be associated with stillbirth were identified. A group of oral anaerobes including Fusobacterium nucleatum were found to be specifically enriched in the cord blood in early preterm live birth. This is by far the most comprehensive study to examine the microbial signatures in umbilical cord blood. Cord blood microbial signatures may be markers for adverse birth outcomes. Detection of key microbial signatures will help identify individuals at risk and develop effective preventative strategies.}, }
@article {pmid35993719, year = {2022}, author = {Baker, JL}, title = {Using Nanopore Sequencing to Obtain Complete Bacterial Genomes from Saliva Samples.}, journal = {mSystems}, volume = {7}, number = {5}, pages = {e0049122}, pmid = {35993719}, issn = {2379-5077}, support = {K99 DE029228/DE/NIDCR NIH HHS/United States ; K99-DE029228//HHS | NIH | National Institute of Dental and Craniofacial Research (NIDCR)/ ; }, mesh = {Humans ; Sequence Analysis, DNA/methods ; *Nanopore Sequencing/methods ; Saliva ; Genome, Bacterial/genetics ; *Microbiota/genetics ; Bacteria/genetics ; }, abstract = {Obtaining complete, high-quality reference genomes is essential to the study of any organism. Recent advances in nanopore sequencing, as well as genome assembly and analysis methods, have made it possible to obtain complete bacterial genomes from metagenomic (i.e., multispecies) samples, including those from the human microbiome. In this study, methods are presented to obtain complete bacterial genomes from human saliva using complementary Oxford Nanopore (ONT) and Illumina sequencing. Applied to 3 human saliva samples, these methods resulted in 11 complete bacterial genomes: 3 Saccharibacteria clade G6 (also known as Ca. Nanogingivalaceae HMT-870), 1 Saccharibacteria clade G1 HMT-348, 2 Rothia mucilaginosa, 2 Actinomyces graevenitzii, 1 Mogibacterium diversum, 1 Lachnospiraceae HMT-096, and 1 Lancefieldella parvula; and one circular chromosome of Ruminococcaceae HMT-075 (which likely has at least 2 chromosomes). The 4 Saccharibacteria genomes, as well as the Actinomyces graeventizii genomes, represented the first complete genomes from their respective bacterial taxa. Aside from the complete genomes, the assemblies contained 147 contigs of over 500,000 bp each and thousands of smaller contigs, together representing a myriad of additional draft genomes including many which are likely nearly complete. The complete genomes enabled highly accurate pangenome analysis, which identified unique and missing features of each genome compared to its closest relatives with complete genomes available in public repositories. These features provide clues as to the lifestyle and ecological role of these bacteria within the human oral microbiota, which will be particularly useful in designing future studies of the taxa that have never been isolated or cultivated. IMPORTANCE Obtaining complete and accurate genomes is crucial to the study of any organism. Previously, obtaining complete genomes of bacteria, including those of the human microbiome, frequently required isolation of the organism, as well as low-throughput, manual sequencing methods to resolve repeat regions. Advancements in long-read sequencing technologies, including Oxford Nanopore (ONT), have made it possible to obtain complete, closed bacterial genomes from metagenomic samples. This study reports methods to obtain complete genomes from the human oral microbiome using complementary ONT and Illumina sequencing of saliva samples. Eleven complete genomes were obtained from 3 human saliva samples, with genomes of Saccharibacteria HMT-870, Saccharibacteria HMT-348, and Actinomyces graeventzii being the first complete genomes from their respective taxa. Obtaining complete bacterial genomes in a high-throughput manner will help illuminate the metabolic and ecological roles of important members of the human microbiota, particularly those that have remained recalcitrant to isolation and cultivation.}, }
@article {pmid35992695, year = {2022}, author = {Puce, L and Hampton-Marcell, J and Trabelsi, K and Ammar, A and Chtourou, H and Boulares, A and Marinelli, L and Mori, L and Cotellessa, F and Currà, A and Trompetto, C and Bragazzi, NL}, title = {Swimming and the human microbiome at the intersection of sports, clinical, and environmental sciences: A scoping review of the literature.}, journal = {Frontiers in microbiology}, volume = {13}, number = {}, pages = {984867}, pmid = {35992695}, issn = {1664-302X}, abstract = {The human microbiota is comprised of more than 10-100 trillion microbial taxa and symbiotic cells. Two major human sites that are host to microbial communities are the gut and the skin. Physical exercise has favorable effects on the structure of human microbiota and metabolite production in sedentary subjects. Recently, the concept of "athletic microbiome" has been introduced. To the best of our knowledge, there exists no review specifically addressing the potential role of microbiomics for swimmers, since each sports discipline requires a specific set of techniques, training protocols, and interactions with the athletic infrastructure/facility. Therefore, to fill in this gap, the present scoping review was undertaken. Four studies were included, three focusing on the gut microbiome, and one addressing the skin microbiome. It was found that several exercise-related variables, such as training volume/intensity, impact the athlete's microbiome, and specifically the non-core/peripheral microbiome, in terms of its architecture/composition, richness, and diversity. Swimming-related power-/sprint- and endurance-oriented activities, acute bouts and chronic exercise, anaerobic/aerobic energy systems have a differential impact on the athlete's microbiome. Therefore, their microbiome can be utilized for different purposes, including talent identification, monitoring the effects of training methodologies, and devising ad hoc conditioning protocols, including dietary supplementation. Microbiomics can be exploited also for clinical purposes, assessing the effects of exposure to swimming pools and developing potential pharmacological strategies to counteract the insurgence of skin infections/inflammation, including acne. In conclusion, microbiomics appears to be a promising tool, even though current research is still limited, warranting, as such, further studies.}, }
@article {pmid35989602, year = {2022}, author = {Lieberman, TD}, title = {Detecting bacterial adaptation within individual microbiomes.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {377}, number = {1861}, pages = {20210243}, pmid = {35989602}, issn = {1471-2970}, support = {DP2 GM140922/GM/NIGMS NIH HHS/United States ; }, mesh = {Acclimatization ; Bacteria/genetics ; Genome ; Genomics ; Humans ; *Microbiota ; }, abstract = {The human microbiome harbours a large capacity for within-person adaptive mutations. Commensal bacterial strains can stably colonize a person for decades, and billions of mutations are generated daily within each person's microbiome. Adaptive mutations emerging during health might be driven by selective forces that vary across individuals, vary within an individual, or are completely novel to the human population. Mutations emerging within individual microbiomes might impact the immune system, the metabolism of nutrients or drugs, and the stability of the community to perturbations. Despite this potential, relatively little attention has been paid to the possibility of adaptive evolution within complex human-associated microbiomes. This review discusses the promise of studying within-microbiome adaptation, the conceptual and technical limitations that may have contributed to an underappreciation of adaptive de novo mutations occurring within microbiomes to date, and methods for detecting recent adaptive evolution. This article is part of a discussion meeting issue 'Genomic population structures of microbial pathogens'.}, }
@article {pmid35987373, year = {2022}, author = {Dalton, KR and Louis, LM and Fandiño-Del-Rio, M and Rule, AM and Pool, W and Randolph, K and Thomas, S and Davis, MF and Quirós-Alcalá, L}, title = {Microbiome alterations from volatile organic compounds (VOC) exposures among workers in salons primarily serving women of color.}, journal = {Environmental research}, volume = {214}, number = {Pt 4}, pages = {114125}, pmid = {35987373}, issn = {1096-0953}, support = {K01 OD019918/OD/NIH HHS/United States ; R01 HD097692/HD/NICHD NIH HHS/United States ; T32 ES007141/ES/NIEHS NIH HHS/United States ; T42 OH008428/OH/NIOSH CDC HHS/United States ; }, mesh = {Female ; Humans ; Biomarkers ; *Microbiota ; *Occupational Exposure/adverse effects/analysis ; RNA, Ribosomal, 16S ; Staphylococcus aureus ; *Volatile Organic Compounds/analysis/toxicity ; Black or African American ; *Beauty Culture ; Ethnic and Racial Minorities ; }, abstract = {Salon workers, especially those serving an ethnically and racially diverse clientele (i.e., Black/Latina), may experience disparately high levels of workplace exposures to respiratory irritants, including volatile organic compounds (VOCs). Salon workers are also reported to have a greater risk of developing respiratory conditions compared to the general population. Emerging evidence suggests that occupational chemical exposures may alter the human microbiome and that these alterations may be an important mechanism by which workplace VOC exposures adversely impact respiratory health. This preliminary research investigated the potential effects of 28 VOC urinary biomarkers on the 16S rRNA nasal microbiome in 40 workers from salons primarily serving women of color (Black and Dominican salons) compared to office workers. Our exploratory analysis revealed significant differences in microbial composition by worker group; namely dissimilar levels of Staphylococcus species (S. epidermidis and S. aureus, specifically) in salon workers compared to office workers, and higher alpha diversity levels in workers in Dominican salons compared to workers in Black salons. Within-sample alpha diversity levels tended to be decreased with higher VOC urinary biomarker concentrations, significantly for carbon disulfide, acrolein, acrylonitrile, crotonaldehyde, and vinyl chloride biomarkers. Our research highlights that occupational exposures, particularly to chemicals like VOCs, can impact the respiratory microbiome in the vulnerable salon worker group. Further understanding of the potential effects of chemical mixtures on microbial composition may provide key insights to respiratory health and other adverse health outcomes, as well as direct prevention efforts in this largely historically understudied occupational population.}, }
@article {pmid35986342, year = {2022}, author = {Che, H and Xiong, Q and Ma, J and Chen, S and Wu, H and Xu, H and Hou, B}, title = {Association of Helicobacter pylori infection with survival outcomes in advanced gastric cancer patients treated with immune checkpoint inhibitors.}, journal = {BMC cancer}, volume = {22}, number = {1}, pages = {904}, pmid = {35986342}, issn = {1471-2407}, mesh = {*Carcinoma, Non-Small-Cell Lung/drug therapy ; *Helicobacter Infections/complications/drug therapy ; *Helicobacter pylori ; Humans ; Immune Checkpoint Inhibitors/therapeutic use ; *Lung Neoplasms/drug therapy ; Prospective Studies ; Retrospective Studies ; *Stomach Neoplasms ; }, abstract = {BACKGROUND: Accumulating evidence has revealed that the gut microbiota influences the effectiveness of immune checkpoint inhibitors (ICIs) in cancer patients. As a part of the human microbiome, Helicobacter pylori (H. pylori) was reported to be associated with reduced effectiveness of anti-PD1 immunotherapy in patients with non-small-cell lung cancer (NSCLC). Gastric cancer is more closely related to H. pylori, so we conducted a retrospective analysis to verify whether the association of H. pylori and effectiveness is applicable to advanced gastric cancer (AGC) patients.<br><br>MATERIAL AND METHODS: AGC patients who had evidence of H. pylori and received anti-PD-1 antibodies were enrolled in the study. The differences in the disease control rate (DCR), overall survival (OS) and progression-free survival (PFS) between the H. pylori-positive group and the negative group were compared.<br><br>RESULTS: A total of 77 patients were included in this study; 34 patients were H. pylori positive, and the prevalence of H. pylori infection was 44.2%. Compared with the H. pylori-negative group, patients in the H. pylori-positive group had a higher risk of nonclinical response to anti-PD-1 antibody, with an OR of 2.91 (95% CI: 1.13-7.50). Patients in the H. pylori-negative group had a longer OS and PFS than those in the positive group, with an estimated median OS of 17.5&#xa0;months vs. 6.2&#xa0;months (HR&#x2009;=&#x2009;2.85, 95% CI: 1.70-4.78; P&#x2009;=&#x2009;0.021) and a median PFS of 8.4&#xa0;months vs. 2.7&#xa0;months (HR&#x2009;=&#x2009;3.11, 95% CI: 1.96-5.07, P&#x2009;=&#x2009;0.008). Multivariate analysis indicated that H. pylori infection was independently associated with PFS (HR&#x2009;=&#x2009;1.90, 95% CI: 1.10-3.30; P&#x2009;=&#x2009;0.022).<br><br>CONCLUSION: Our study unveils for the first time that H. pylori infection is associated with the outcome of immunotherapy for AGC patients. Multicenter, large sample and prospective clinical studies are needed to verify the association.}, }
@article {pmid35984746, year = {2022}, author = {Scheithauer, TPM and Herrema, H and Yu, H and Bakker, GJ and Winkelmeijer, M and Soukhatcheva, G and Dai, D and Ma, C and Havik, SR and Balvers, M and Davids, M and Meijnikman, AS and Aydin, &#xd6; and van den Born, BH and Besselink, MG and Busch, OR and de Brauw, M and van de Laar, A and Belzer, C and Stahl, M and de Vos, WM and Vallance, BA and Nieuwdorp, M and Verchere, CB and van Raalte, DH}, title = {Gut-derived bacterial flagellin induces beta-cell inflammation and dysfunction.}, journal = {Gut microbes}, volume = {14}, number = {1}, pages = {2111951}, pmid = {35984746}, issn = {1949-0984}, mesh = {Animals ; Bacterial Proteins/genetics/metabolism ; *Diabetes Mellitus, Type 2/microbiology ; *Flagellin/genetics/metabolism ; *Gastrointestinal Microbiome ; Humans ; Inflammation/metabolism ; Insulin ; *Insulin-Secreting Cells/metabolism ; Mice ; }, abstract = {Hyperglycemia and type 2 diabetes (T2D) are caused by failure of pancreatic beta cells. The role of the gut microbiota in T2D has been studied, but causal links remain enigmatic. Obese individuals with or without T2D were included from two independent Dutch cohorts. Human data were translated in vitro and in vivo by using pancreatic islets from C57BL6/J mice and by injecting flagellin into obese mice. Flagellin is part of the bacterial locomotor appendage flagellum, present in gut bacteria including Enterobacteriaceae, which we show to be more abundant in the gut of individuals with T2D. Subsequently, flagellin induces a pro-inflammatory response in pancreatic islets mediated by the Toll-like receptor (TLR)-5 expressed on resident islet macrophages. This inflammatory response is associated with beta-cell dysfunction, characterized by reduced insulin gene expression, impaired proinsulin processing and stress-induced insulin hypersecretion in vitro and in vivo in mice. We postulate that increased systemically disseminated flagellin in T2D is a contributing factor to beta-cell failure in time and represents a novel therapeutic target.}, }
@article {pmid35982466, year = {2022}, author = {Hurley, JC}, title = {Candida and the Gram-positive trio: testing the vibe in the ICU patient microbiome using structural equation modelling of literature derived data.}, journal = {Emerging themes in epidemiology}, volume = {19}, number = {1}, pages = {7}, pmid = {35982466}, issn = {1742-7622}, abstract = {BACKGROUND: Whether Candida interacts with Gram-positive bacteria, such as Staphylococcus aureus, coagulase negative Staphylococci (CNS) and Enterococci, to enhance their invasive potential from the microbiome of ICU patients remains unclear. Several effective anti-septic, antibiotic, anti-fungal, and non-decontamination based interventions studied for prevention of ventilator associated pneumonia (VAP) and other ICU acquired infections among patients receiving prolonged mechanical ventilation (MV) are known to variably impact Candida colonization. The collective observations within control and intervention groups from numerous ICU infection prevention studies enables tests of these postulated microbial interactions in the clinical context.<br><br>METHODS: Four candidate generalized structural equation models (GSEM), each with Staphylococcus aureus, CNS and Enterococci colonization, defined as latent variables, were confronted with blood culture and respiratory tract isolate data derived from 460 groups of ICU patients receiving prolonged MV from 283 infection prevention studies.<br><br>RESULTS: Introducing interaction terms between Candida colonization and each of S aureus (coefficient&#x2009;+&#x2009;0.40; 95% confidence interval&#x2009;+&#x2009;0.24 to&#x2009;+&#x2009;0.55), CNS (+&#x2009;0.68;&#x2009;+&#x2009;0.34 to&#x2009;+&#x2009;1.0) and Enterococcal (+&#x2009;0.56;&#x2009;+&#x2009;0.33 to&#x2009;+&#x2009;0.79) colonization (all as latent variables) improved the fit for each model. The magnitude and significance level of the interaction terms were similar to the positive associations between exposure to topical antibiotic prophylaxis (TAP) on Enterococcal (+&#x2009;0.51;&#x2009;+&#x2009;0.12 to&#x2009;+&#x2009;0.89) and Candida colonization (+&#x2009;0.98;&#x2009;+&#x2009;0.35 to&#x2009;+&#x2009;1.61) versus the negative association of TAP with S aureus (-&#xa0;0.45; -&#xa0;0.70 to -&#xa0;0.20) colonization and the negative association of anti-fungal exposure and Candida colonization (-&#xa0;1.41; -&#xa0;1.6 to -&#xa0;0.72).<br><br>CONCLUSIONS: GSEM modelling of published ICU infection prevention data enables the postulated interactions between Candida and Gram-positive bacteria to be tested using clinically derived data. The optimal model implies interactions occurring in the human microbiome facilitating bacterial invasion and infection. This interaction might also account for the paradoxically high bacteremia incidences among studies of TAP in ICU patients.}, }
@article {pmid35978666, year = {2022}, author = {Maslennikov, R and Ivashkin, V and Alieva, A and Poluektova, E and Kudryavtseva, A and Krasnov, G and Zharkova, M and Zharikov, Y}, title = {Gut dysbiosis and body composition in cirrhosis.}, journal = {World journal of hepatology}, volume = {14}, number = {6}, pages = {1210-1225}, pmid = {35978666}, issn = {1948-5182}, abstract = {BACKGROUND: Gut dysbiosis and changes in body composition (i.e., a decrease in the proportion of muscle mass and an increase in extracellular fluid) are common in cirrhosis.<br><br>AIM: To study the relationship between the gut microbiota and body composition in cirrhosis.<br><br>METHODS: This observational study included 46 patients with cirrhosis. Stool microbiome was assessed using 16S rRNA gene sequencing. Multifrequency bioelectrical impedance analysis was performed to assess body composition in these patients.<br><br>RESULTS: An increase in fat mass and a decrease in body cell mass were noted in 23/46 (50.0%) and 15/46 (32.6%) patients, respectively. Changes in the gut microbiome were not independently associated with the fat mass percentage in cirrhosis. The abundance of Bacteroidaceae (P = 0.041) and Eggerthella (P = 0.001) increased, whereas that of Erysipelatoclostridiaceae (P = 0.006), Catenibacterium (P = 0.021), Coprococcus (P = 0.033), Desulfovibrio (P = 0.043), Intestinimonas (P = 0.028), and Senegalimassilia (P = 0.015) decreased in the gut microbiome of patients with body cell mass deficiency. The amount of extracellular fluid increased in 22/46 (47.6%) patients. Proteobacteria abundance (P < 0.001) increased, whereas Firmicutes (P = 0.023), Actinobacteria (P = 0.026), Bacilli (P = 0.008), Anaerovoraceceae (P = 0.027), Christensenellaceae (P = 0.038), Eggerthellaceae (P = 0.047), Erysipelatoclostridiaceae (P = 0.015), Erysipelotrichaceae (P = 0.003), Oscillospiraceae (P = 0.024), Rikenellaceae (P = 0.002), Collinsella (P = 0.030), Hungatella (P = 0.040), Peptococcaceae (P = 0.023), Slackia (P = 0.008), and Senegalimassilia (P = 0.024) abundance decreased in these patients. Patients with clinically significant ascites (n = 9) had a higher abundance of Proteobacteria (P = 0.031) and a lower abundance of Actinobacteria (P = 0.019) and Bacteroidetes (P = 0.046) than patients without clinically significant ascites (n = 37).<br><br>CONCLUSION: Changes in the amount of body cell mass and extracellular fluid are associated with changes in the gut microbiome in cirrhosis patients.}, }
@article {pmid35978282, year = {2022}, author = {Nel Van Zyl, K and Whitelaw, AC and Hesseling, AC and Seddon, JA and Demers, AM and Newton-Foot, M}, title = {Fungal diversity in the gut microbiome of young South African children.}, journal = {BMC microbiology}, volume = {22}, number = {1}, pages = {201}, pmid = {35978282}, issn = {1471-2180}, support = {/WT_/Wellcome Trust/United Kingdom ; MR/M007340/1/MRC_/Medical Research Council/United Kingdom ; MR/R007942/1/MRC_/Medical Research Council/United Kingdom ; UM1 AI106716/AI/NIAID NIH HHS/United States ; }, mesh = {Adolescent ; Bacteria/genetics ; Candida ; Child ; Female ; Fungi/genetics ; *Gastrointestinal Microbiome ; Humans ; *Microbiota ; South Africa ; Vitamin A ; }, abstract = {BACKGROUND: The fungal microbiome, or mycobiome, is a poorly described component of the gut ecosystem and little is known about its structure and development in children. In South Africa, there have been no culture-independent evaluations of the child gut mycobiota. This study aimed to characterise the gut mycobiota and explore the relationships between fungi and bacteria in the gut microbiome of children from Cape Town communities.<br><br>METHODS: Stool samples were collected from children enrolled in the TB-CHAMP clinical trial. Internal transcribed spacer 1 (ITS1) gene sequencing was performed on a total of 115 stool samples using the Illumina MiSeq platform. Differences in fungal diversity and composition in relation to demographic, clinical, and environmental factors were investigated, and correlations between fungi and previously described bacterial populations in the same samples were described.<br><br>RESULTS: Taxa from the genera Candida and Saccharomyces were detected in all participants. Differential abundance analysis showed that Candida&#xa0;spp. were significantly more abundant in children younger than 2&#xa0;years compared to older children. The gut mycobiota was less diverse than the bacterial microbiota of the same participants, consistent with the findings of other human microbiome studies. The variation in richness and evenness of fungi was substantial, even between individuals of the same age. There was significant association between vitamin A supplementation and higher fungal alpha diversity (p&#x2009;=&#x2009;0.047), and girls were shown to have lower fungal alpha diversity (p&#x2009;=&#x2009;0.003). Co-occurrence between several bacterial taxa and Candida albicans was observed.<br><br>CONCLUSIONS: The dominant fungal taxa in our study population were similar to those reported in other paediatric studies; however, it remains difficult to identify the true core gut mycobiota due to the challenges set by the low abundance of gut fungi and the lack of true gut colonising species. The connection between the microbiota, vitamin A supplementation, and growth and immunity warrants exploration, especially in populations at risk for micronutrient deficiencies. While we were able to provide insight into the gut mycobiota of young South African children, further functional studies are necessary to explain the role of the mycobiota and the correlations between bacteria and fungi in human health.}, }
@article {pmid35975994, year = {2022}, author = {Hendrickson, EL and Bor, B and Kerns, KA and Lamont, EI and Chang, Y and Liu, J and Cen, L and Schulte, F and Hardt, M and Shi, W and He, X and McLean, JS}, title = {Transcriptome of Epibiont Saccharibacteria Nanosynbacter lyticus Strain TM7x During the Establishment of Symbiosis.}, journal = {Journal of bacteriology}, volume = {204}, number = {9}, pages = {e0011222}, pmid = {35975994}, issn = {1098-5530}, support = {K99 DE027719/DE/NIDCR NIH HHS/United States ; R01 AI087946/AI/NIAID NIH HHS/United States ; T90 DE021984/DE/NIDCR NIH HHS/United States ; KL2 TR000421/TR/NCATS NIH HHS/United States ; R00 DE027719/DE/NIDCR NIH HHS/United States ; R01 DE023810/DE/NIDCR NIH HHS/United States ; R01 AI132818/AI/NIAID NIH HHS/United States ; R01 DE031274/DE/NIDCR NIH HHS/United States ; S10 OD023603/OD/NIH HHS/United States ; KL2 TR002317/TR/NCATS NIH HHS/United States ; }, mesh = {Arginine/metabolism ; Bacteria/genetics ; Genome, Bacterial ; Humans ; Peptidoglycan/metabolism ; *Symbiosis ; *Transcriptome ; }, abstract = {Saccharibacteria Nanosynbacter lyticus strain TM7x is a member of the broadly distributed candidate phylum radiation. These bacteria have ultrasmall cell sizes, have reduced genomes, and live as epibionts on the surfaces of other bacteria. The mechanisms by which they establish and maintain this relationship are not yet fully understood. The transcriptomes of the epibiont TM7x and its host bacteria Schaalia odontolytica strain XH001 were captured across the establishment of symbiosis during both the initial interaction and stable symbiosis. The results showed a dynamic interaction with large shifts in gene expression for both species between the initial encounter and stable symbiosis, notably in transporter genes. During stable symbiosis, the host XH001 showed higher gene expression for peptidoglycan biosynthesis, mannosylation, cell cycle and stress-related genes, whereas it showed lower expression of chromosomal partitioning genes. This was consistent with the elongated cell shape seen in XH001 infected with TM7x and our discovery that infection resulted in thickened cell walls. Within TM7x, increased pili, type IV effector genes, and arginine catabolism/biosynthesis gene expression during stable symbiosis implied a key role for these functions in the interaction. Consistent with its survival and persistence in the human microbiome as an obligate epibiont with reduced de novo biosynthetic capacities, TM7x also showed higher levels of energy production and peptidoglycan biosynthesis, but lower expression of stress-related genes, during stable symbiosis. These results imply that TM7x and its host bacteria keep a delicate balance in order to sustain an episymbiotic lifestyle. IMPORTANCE Nanosynbacter lyticus type strain TM7x is the first cultivated member of the Saccharibacteria and the candidate phyla radiation (CPR). It was discovered to be ultrasmall in cell size with a highly reduced genome that establishes an obligate epibiotic relationship with its host bacterium. The CPR is a large, monophyletic radiation of bacteria with reduced genomes that includes Saccharibacteria. The vast majority of the CPR have yet to be cultivated, and our insights into these unique organisms to date have been derived from only a few Saccharibacteria species. Being obligate parasites, it is unknown how these ultrasmall Saccharibacteria, which are missing many de novo biosynthetic pathways, are maintained at a high prevalence within the human microbiome as well as in the environment.}, }
@article {pmid35968909, year = {2022}, author = {Zhang, Y and Li, P and Ma, Y and Wang, J and Chen, Y}, title = {Artificial intelligence accelerates the mining of bioactive small molecules from human microbiome.}, journal = {Clinical and translational medicine}, volume = {12}, number = {8}, pages = {e1011}, pmid = {35968909}, issn = {2001-1326}, mesh = {*Artificial Intelligence ; Humans ; *Microbiota ; }, }
@article {pmid35966698, year = {2022}, author = {Jones, J and Reinke, SN and Mousavi-Derazmahalleh, M and Palmer, DJ and Christophersen, CT}, title = {Changes to the Gut Microbiome in Young Children Showing Early Behavioral Signs of Autism.}, journal = {Frontiers in microbiology}, volume = {13}, number = {}, pages = {905901}, pmid = {35966698}, issn = {1664-302X}, abstract = {The human gut microbiome has increasingly been associated with autism spectrum disorder (ASD), which is a neurological developmental disorder, characterized by impairments to social interaction. The ability of the gut microbiota to signal across the gut-brain-microbiota axis with metabolites, including short-chain fatty acids, impacts brain health and has been identified to play a role in the gastrointestinal and developmental symptoms affecting autistic children. The fecal microbiome of older children with ASD has repeatedly shown particular shifts in the bacterial and fungal microbial community, which are significantly different from age-matched neurotypical controls, but it is still unclear whether these characteristic shifts are detectable before diagnosis. Early microbial colonization patterns can have long-lasting effects on human health, and pre-emptive intervention may be an important mediator to more severe autism. In this study, we characterized both the microbiome and short-chain fatty acid concentrations of fecal samples from young children between 21 and 40 months who were showing early behavioral signs of ASD. The fungal richness and acetic acid concentrations were observed to be higher with increasing autism severity, and the abundance of several bacterial taxa also changed due to the severity of ASD. Bacterial diversity and SCFA concentrations were also associated with stool form, and some bacterial families were found with differential abundance according to stool firmness. An exploratory analysis of the microbiome associated with pre-emptive treatment also showed significant differences at multiple taxonomic levels. These differences may impact the microbial signaling across the gut-brain-microbiota axis and the neurological development of the children.}, }
@article {pmid35966676, year = {2022}, author = {Wei, Q and Li, Z and Gu, Z and Liu, X and Krutmann, J and Wang, J and Xia, J}, title = {Shotgun metagenomic sequencing reveals skin microbial variability from different facial sites.}, journal = {Frontiers in microbiology}, volume = {13}, number = {}, pages = {933189}, pmid = {35966676}, issn = {1664-302X}, abstract = {Biogeography (body site) is known to be one of the main factors influencing the composition of the skin microbial community. However, site-associated microbial variability at a fine-scale level was not well-characterized since there was a lack of high-resolution recognition of facial microbiota across kingdoms by shotgun metagenomic sequencing. To investigate the explicit microbial variance in the human face, 822 shotgun metagenomic sequencing data from Han Chinese recently published by our group, in combination with 97 North American samples from NIH Human Microbiome Project (HMP), were reassessed. Metagenomic profiling of bacteria, fungi, and bacteriophages, as well as enriched function modules from three facial sites (forehead, cheek, and the back of the nose), was analyzed. The results revealed that skin microbial features were more alike in the forehead and cheek while varied from the back of the nose in terms of taxonomy and functionality. Analysis based on biogeographic theories suggested that neutral drift with niche selection from the host could possibly give rise to the variations. Of note, the abundance of porphyrin-producing species, i.e., Cutibacterium acnes, Cutibacterium avidum, Cutibacterium granulosum, and Cutibacterium namnetense, was all the highest in the back of the nose compared with the forehead/cheek, which was consistent with the highest porphyrin level on the nose in our population. Sequentially, the site-associated microbiome variance was confirmed in American populations; however, it was not entirely consistent. Furthermore, our data revealed correlation patterns between Propionibacterium acnes bacteriophages with genus Cutibacterium at different facial sites in both populations; however, C. acnes exhibited a distinct correlation with P. acnes bacteriophages in Americans/Chinese. Taken together, in this study, we explored the fine-scale facial site-associated changes in the skin microbiome and provided insight into the ecological processes underlying facial microbial variations.}, }
@article {pmid35964945, year = {2022}, author = {Kapoor, B and Gulati, M and Rani, P and Gupta, R}, title = {Psoriasis: Interplay between dysbiosis and host immune system.}, journal = {Autoimmunity reviews}, volume = {21}, number = {11}, pages = {103169}, doi = {10.1016/j.autrev.2022.103169}, pmid = {35964945}, issn = {1873-0183}, mesh = {Humans ; Dysbiosis/complications ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Prebiotics ; *Probiotics/therapeutic use ; *Psoriasis ; Immune System ; Bacteria ; }, abstract = {With advancement in human microbiome research, an increasing number of scientific evidences have endorsed the key role of both gut and skin microbiota in the pathogenesis of psoriasis. Microbiome dysbiosis, characterized by altered diversity and composition, as well as rise of pathobionts, have been identified as possible triggers for recurrent episodes of psoriasis. Mechanistically, gut dysbiosis leads to "leaky gut syndrome" via disruption of epithelial bilayer, thereby, resulting in translocation of bacteria and other endotoxins to systemic circulation, which in turn, results in inflammatory response. Similarly, skin dysbiosis disrupts the cutaneous homeostasis, leading to invasion of bacteria and other pathogens to deeper layers of skin or even systemic circulation further enhanced by injury caused by pruritus-induced scratching, and elicit innate and adaptive inflammation. The present review explores the correlation of both skin and gut microbiota dysbiosis with psoriasis. Also, the studies highlighting the potential of bacteriotherapeutic approaches including probiotics, prebiotics, metabiotics, and fecal microbiota transplantation for the management of psoriasis have been discussed.}, }
@article {pmid35959873, year = {2022}, author = {Mashyn, S and Borodanov, S and Klymenko, O and Lev, I and Shipova, K}, title = {THE ROLE OF LACTOBACILLI IN THE HUMAN MICROBIOME AND METHODS OF THEIR CULTIVATION AND PRESERVATION.}, journal = {Georgian medical news}, volume = {}, number = {326}, pages = {23-35}, pmid = {35959873}, issn = {1512-0112}, mesh = {Bacteria ; Humans ; Lactobacillus/physiology ; *Microbiota ; *Probiotics ; }, abstract = {The extremely important role of the microbiome for human life and health has long been known. Many studies around the world are devoted to studying the mechanisms of action and functions of various bacteria that are permanent residents of our body. Connections between the bacteria of our microbiome and all organs and systems of the human body (intestine, brain, nervous and cardiovascular systems) have been identified. However, the effect of bacteria can be positive or negative, which affects the emergence and development of diseases or promotes healing. Genus Lactobacillus is one of the most numerous populations of bacteria in the human body. Moreover, they have a significant positive effect on health. Scientists are actively researching methods of cultivating and using bacteria of this genus in the pharmaceutical and industrial fields. Most probiotics contain lactobacilli strains. Therefore, the study of methods of cultivation and storage of lactobacilli in order to find ways to improve their viability and functionality and, at the same time, the invention of options to protect cell culture from various harmful factors is extremely important. In our review, we considered the importance of the microbiome for human health and the role of bacteria of the genus Lactobacillus as its component. Scientific works on studying the mechanisms of influence of lactobacilli on the functional capacity of human organs and systems have been studied. Much of the review is devoted to the study of lactobacilli cultivation methods, the diversity of culture media, and the importance of their components to improve the viability of lactobacilli culture because they are quite demanding and vulnerable. Attention is also paid to the development of methods of storage of grown cultures of bacterial cells and their improvement in order to obtain functional and suitable for further use in the pharmacological and industrial areas of bacterial strains.}, }
@article {pmid35958597, year = {2022}, author = {Livson, S and Virtanen, S and Lokki, AI and Holster, T and Rahkonen, L and Kalliala, I and Nieminen, P and Salonen, A and Meri, S}, title = {Cervicovaginal Complement Activation and Microbiota During Pregnancy and in Parturition.}, journal = {Frontiers in immunology}, volume = {13}, number = {}, pages = {925630}, pmid = {35958597}, issn = {1664-3224}, mesh = {Bacteria/genetics ; Complement Activation ; *Complement Factor B ; Female ; Gardnerella vaginalis/genetics ; Humans ; Intracellular Signaling Peptides and Proteins ; LIM Domain Proteins ; *Microbiota/genetics ; Muscle Proteins ; Parturition ; Pregnancy ; Vagina/microbiology ; }, abstract = {BACKGROUND: Vaginal microbiome and the local innate immune defense, including the complement system, contribute to anti- and proinflammatory homeostasis during pregnancy and parturition. The relationship between commensal vaginal bacteria and complement activation during pregnancy and delivery is not known.<br><br>OBJECTIVE: To study the association of the cervicovaginal microbiota composition to activation and regulation of the complement system during pregnancy and labor.<br><br>STUDY DESIGN: We recruited women during late pregnancy (weeks 41 + 5 to 42 + 0, n=48) and women in active labor (weeks 38 + 4 to 42 + 2, n=25). Mucosal swabs were taken from the external cervix and lateral fornix of the vagina. From the same sampling site, microbiota was analyzed with 16S RNA gene amplicon sequencing. A Western blot technique was used to detect complement C3, C4 and factor B activation and presence of complement inhibitors. For semiquantitative analysis, the bands of the electrophoresed proteins in gels were digitized on a flatbed photo scanner and staining intensities were analyzed using ImageJ/Fiji win-64 software. Patient data was collected from medical records and questionnaires.<br><br>RESULTS: The vaginal microbiota was Lactobacillus-dominant in most of the samples (n=60), L. iners and L. crispatus being the dominant species. L. gasseri and L. jensenii were found to be more abundant during pregnancy than active labor. L. jensenii abundance correlated with C4 activation during pregnancy but not in labor. Gardnerella vaginalis was associated with C4 activation both during pregnancy and labor. The amount of L. gasseri correlated with factor B activation during pregnancy but not during labor. Atopobium vaginae was more abundant during pregnancy than labor and correlated with C4 activation during labor and with factor B activation during pregnancy. Activation of the alternative pathway factor B was significantly stronger during pregnancy compared to labor. During labor complement activation may be inhibited by the abundant presence of factor H and FHL1.<br><br>CONCLUSIONS: These results indicate that bacterial composition of the vaginal microbiota could have a role in the local activation and regulation of complement-mediated inflammation during pregnancy. At the time of parturition complement activation appears to be more strictly regulated than during pregnancy.}, }
@article {pmid35951092, year = {2022}, author = {Parker, KD and Mueller, JL and Westfal, M and Goldstein, AM and Ward, NL}, title = {A pilot study characterizing longitudinal changes in fecal microbiota of patients with Hirschsprung-associated enterocolitis.}, journal = {Pediatric surgery international}, volume = {38}, number = {11}, pages = {1541-1553}, pmid = {35951092}, issn = {1437-9813}, support = {DK098696-01A1/GM/NIGMS NIH HHS/United States ; 2P20GM103432/GM/NIGMS NIH HHS/United States ; DK098696-01A1/GM/NIGMS NIH HHS/United States ; 2P20GM103432/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Child ; *Enterocolitis/etiology ; Feces ; *Hirschsprung Disease/surgery ; Humans ; Mice ; *Microbiota ; Pilot Projects ; }, abstract = {PURPOSE: Hirschsprung disease is a neurointestinal disease that occurs due to failure of enteric neural crest-derived cells to complete their rostrocaudal migration along the gut mesenchyme, resulting in aganglionosis along variable lengths of the distal bowel. Despite the effective surgery that removes the aganglionic segment, children with Hirschsprung disease remain at high risk for developing a potentially life-threatening enterocolitis (Hirschsprung-associated enterocolitis). Although the etiology of this enterocolitis remains poorly understood, several recent studies in both mouse models and in human subjects suggest potential involvement of gastrointestinal microbiota in the underlying pathogenesis of Hirschsprung-associated enterocolitis.<br><br>METHODS: We present the first study to exploit the Illumina MiSeq next-generation sequencing platform within a longitudinal framework focused on microbiomes of Hirschsprung-associated enterocolitis in five patients. We analyzed bacterial communities from fecal samples collected at different timepoints starting from active enterocolitis and progressing into remission.<br><br>RESULTS: We observed compositional differences between patients largely attributable to variability in age at the time of sample collection. Remission samples across patients exhibited compositional similarity, including enrichment of Blautia, while active enterocolitis samples showed substantial variability in composition.<br><br>CONCLUSIONS: Overall, our findings provide continued support for the role of GI microbiota in the pathogenesis of Hirschsprung-associated enterocolitis.}, }
@article {pmid35947353, year = {2023}, author = {Dickerson, F and Dilmore, AH and Godoy-Vitorino, F and Nguyen, TT and Paulus, M and Pinto-Tomas, AA and Moya-Roman, C and Zuniga-Chaves, I and Severance, EG and Jeste, DV}, title = {The Microbiome and Mental Health Across the Lifespan.}, journal = {Current topics in behavioral neurosciences}, volume = {61}, number = {}, pages = {119-140}, pmid = {35947353}, issn = {1866-3370}, mesh = {Humans ; Aged ; Longevity ; Mental Health ; *Alzheimer Disease ; *Microbiota ; *Schizophrenia ; }, abstract = {INTRODUCTION: The combined genetic material of the microorganisms in the human body, known as the microbiome, is being increasingly recognized as a major determinant of human health and disease. Although located predominantly on mucosal surfaces, these microorganisms have profound effects on brain functioning through the gut-brain axis.<br><br>METHOD: The content of the chapter is based on a study group session at the annual meeting of the American College of Neuropsychopharmacology (ACNP). The objective was to discuss the emerging relationship between the human microbiome and mental health as relevant to ACNP's interests in developing and evaluating novel neuropsychiatric treatment strategies. The focus is on specific brain disorders, such as schizophrenia, substance use, and Alzheimer's disease, as well as on broader clinical issues such as suicidality, loneliness and wisdom in old age, and longevity.<br><br>RESULTS: Studies of schizophrenia indicate that the microbiome of individuals with this disorder differs from that of non-psychiatric comparison groups in terms of diversity and composition. Differences are also found in microbial metabolic pathways. An early study in substance use disorders found that individuals with this disorder have lower levels of beta diversity in their oral microbiome than a comparison group. This measure, along with others, was used to distinguish individuals with substance use disorders from controls. In terms of suicidality, there is preliminary evidence that persons who have made a suicide attempt differ from psychiatric and non-psychiatric comparison groups in measures of beta diversity. Exploratory studies in Alzheimer's disease indicate that gut microbes may contribute to disease pathogenesis by regulating innate immunity and neuroinflammation and thus influencing brain function. In another study looking at the microbiome in older adults, positive associations were found between wisdom and alpha diversity and negative associations with subjective loneliness. In other studies of older adults, here with a focus on longevity, individuals with healthy aging and unusually long lives had an abundance of specific microorganisms which distinguished them from other individuals.<br><br>DISCUSSION: Future studies would benefit from standardizing methods of sample collection, processing, and analysis. There is also a need for the standardized collection of relevant demographic and clinical data, including diet, medications, cigarette smoking, and other potentially confounding factors. While still in its infancy, research to date indicates a role for the microbiome in mental health disorders and conditions. Interventions are available which can modulate the microbiome and lead to clinical improvements. These include microbiome-altering medications as well as probiotic microorganisms capable of modulating the inflammation in the brain through the gut-brain axis. This research holds great promise in terms of developing new methods for the prevention and treatment of a range of human brain disorders.}, }
@article {pmid35945268, year = {2023}, author = {Turunen, J and Tejesvi, MV and Suokas, M and Virtanen, N and Paalanne, N and Kaisanlahti, A and Reunanen, J and Tapiainen, T}, title = {Bacterial extracellular vesicles in the microbiome of first-pass meconium in newborn infants.}, journal = {Pediatric research}, volume = {93}, number = {4}, pages = {887-896}, pmid = {35945268}, issn = {1530-0447}, mesh = {Infant, Newborn ; Pregnancy ; Female ; Infant ; Humans ; *Meconium/microbiology ; RNA, Ribosomal, 16S/genetics ; *Microbiota ; Bacteria/genetics ; Anti-Bacterial Agents ; }, abstract = {BACKGROUND: Bacterial extracellular vesicles (EVs) are more likely to cross biological barriers than whole-cell bacteria. We previously observed EV-sized particles by electron microscopy in the first-pass meconium of newborn infants. We hypothesized that EVs may be of bacterial origin and represent a novel entity in the human microbiome during fetal and perinatal periods.<br><br>METHODS: We extracted EVs from first-pass meconium samples of 17 newborn infants and performed bacterial 16S rRNA gene sequencing of the vesicles. We compared the EV content from the meconium samples of infants based on the delivery mode, and in vaginal delivery samples, based on the usage of intrapartum antibiotics.<br><br>RESULTS: We found bacterial EVs in all first-pass meconium samples. All EV samples had bacterial RNA. Most of the phyla present in the samples were Firmicutes (62%), Actinobacteriota (18%), Proteobacteria (10%), and Bacteroidota (7.3%). The most abundant genera were Streptococcus (21%) and Staphylococcus (17%). The differences between the delivery mode and exposure to antibiotics were not statistically significant.<br><br>CONCLUSIONS: Bacterial EVs were present in the first-pass meconium of newborn infants. Bacterial EVs may represent an important novel feature of the gut microbiome during fetal and perinatal periods.<br><br>IMPACT: We show that bacterial extracellular vesicles are present in the microbiome of first-pass meconium in newborn infants. This is a novel finding. To our knowledge, this is the first study to report the presence of bacterial extracellular vesicles in the gut microbiome during fetal and perinatal periods. This finding is important because bacterial extracellular vesicles are more likely to cross biological barriers than whole-cell bacteria. Thus, the early gut microbiome may potentially interact with the host through bacterial EVs.}, }
@article {pmid35936744, year = {2022}, author = {Zhou, X and Kandalai, S and Hossain, F and Zheng, Q}, title = {Tumor microbiome metabolism: A game changer in cancer development and therapy.}, journal = {Frontiers in oncology}, volume = {12}, number = {}, pages = {933407}, pmid = {35936744}, issn = {2234-943X}, abstract = {Accumulating recent evidence indicates that the human microbiome plays essential roles in pathophysiological states, including cancer. The tumor microbiome, an emerging concept that has not yet been clearly defined, has been proven to influence both cancer development and therapy through complex mechanisms. Small molecule metabolites produced by the tumor microbiome through unique biosynthetic pathways can easily diffuse into tissues and penetrate cell membranes through transporters or free diffusion, thus remodeling the signaling pathways of cancer and immune cells by interacting with biomacromolecules. Targeting tumor microbiome metabolism could offer a novel perspective for not only understanding cancer progression but also developing new strategies for the treatment of multiple cancer types. Here, we summarize recent advances regarding the role the tumor microbiome plays as a game changer in cancer biology. Specifically, the metabolites produced by the tumor microbiome and their potential effects on the cancer development therapy are discussed to understand the importance of the microbial metabolism in the tumor microenvironment. Finally, new anticancer therapeutic strategies that target tumor microbiome metabolism are reviewed and proposed to provide new insights in clinical applications.}, }
@article {pmid35935217, year = {2022}, author = {Buttimer, C and Sutton, T and Colom, J and Murray, E and Bettio, PH and Smith, L and Bolocan, AS and Shkoporov, A and Oka, A and Liu, B and Herzog, JW and Sartor, RB and Draper, LA and Ross, RP and Hill, C}, title = {Impact of a phage cocktail targeting Escherichia coli and Enterococcus faecalis as members of a gut bacterial consortium in vitro and in vivo.}, journal = {Frontiers in microbiology}, volume = {13}, number = {}, pages = {936083}, pmid = {35935217}, issn = {1664-302X}, support = {P01 DK094779/DK/NIDDK NIH HHS/United States ; P30 DK034987/DK/NIDDK NIH HHS/United States ; P40 OD010995/OD/NIH HHS/United States ; }, abstract = {Escherichia coli and Enterococcus faecalis have been implicated as important players in human gut health that have been associated with the onset of inflammatory bowel disease (IBD). Bacteriophage (phage) therapy has been used for decades to target pathogens as an alternative to antibiotics, but the ability of phage to shape complex bacterial consortia in the lower gastrointestinal tract is not clearly understood. We administered a cocktail of six phages (either viable or heat-inactivated) targeting pro-inflammatory Escherichia coli LF82 and Enterococcus faecalis OG1RF as members of a defined community in both a continuous fermenter and a murine colitis model. The two target strains were members of a six species simplified human microbiome consortium (SIHUMI-6). In a 72-h continuous fermentation, the phage cocktail caused a 1.1 and 1.5 log (log10 genome copies/mL) reduction in E. faecalis and E. coli numbers, respectively. This interaction was accompanied by changes in the numbers of other SIHUMI-6 members, with an increase of Lactiplantibacillus plantarum (1.7 log) and Faecalibacterium prausnitzii (1.8 log). However, in germ-free mice colonized by the same bacterial consortium, the same phage cocktail administered twice a week over nine weeks did not cause a significant reduction of the target strains. Mice treated with active or inactive phage had similar levels of pro-inflammatory cytokines (IFN-y/IL12p40) in unstimulated colorectal colonic strip cultures. However, histology scores of the murine lower GIT (cecum and distal colon) were lower in the viable phage-treated mice, suggesting that the phage cocktail did influence the functionality of the SIHUMI-6 consortium. For this study, we conclude that the observed potential of phages to reduce host populations in in vitro models did not translate to a similar outcome in an in vivo setting, with this effect likely brought about by the reduction of phage numbers during transit of the mouse GIT.}, }
@article {pmid35934639, year = {2022}, author = {Peuranpää, P and Holster, T and Saqib, S and Kalliala, I and Tiitinen, A and Salonen, A and Hautamäki, H}, title = {Female reproductive tract microbiota and recurrent pregnancy loss: a nested case-control study.}, journal = {Reproductive biomedicine online}, volume = {45}, number = {5}, pages = {1021-1031}, doi = {10.1016/j.rbmo.2022.06.008}, pmid = {35934639}, issn = {1472-6491}, mesh = {Pregnancy ; Female ; Humans ; Case-Control Studies ; RNA, Ribosomal, 16S/genetics ; *Microbiota ; Vagina/microbiology ; *Abortion, Habitual ; }, abstract = {RESEARCH QUESTION: Is the composition of the endometrial or vaginal microbiota associated with recurrent pregnancy loss (RPL)?<br><br>DESIGN: Endometrial and vaginal samples were collected from 47 women with two or more consecutive pregnancy losses and 39 healthy control women without a history of pregnancy loss, between March 2018 and December 2020 at Helsinki University Hospital, Helsinki, Finland. The compositions of the endometrial and vaginal microbiota, analysed using 16S rRNA gene amplicon sequencing, were compared between the RPL and control women, and between individual vaginal and endometrial samples. The mycobiota composition was analysed using internal transcribed spacer 1 amplicon sequencing for a descriptive summary. The models were adjusted for body mass index, age and parity. False discovery rate-corrected P-values (q-values) were used to define nominal statistical significance at q&#xa0;<&#xa0;0.05.<br><br>RESULTS: Lactobacillus crispatus was less abundant in the endometrial samples of women with RPL compared with controls (mean relative abundance 17.2% versus 45.6%, q&#x202f;=&#x202f;0.04). Gardnerella vaginalis was more abundant in the RPL group than in controls in both endometrial (12.4% versus 5.8%, q&#xa0;<&#xa0;0.001) and vaginal (8.7% versus 5.7%, q&#x202f;=&#x202f;0.002) samples. The individual vaginal and endometrial microbial compositions correlated strongly (R&#x202f;=&#x202f;0.85, P&#xa0;<&#xa0;0.001). Fungi were detected in 22% of the endometrial and 36% of the vaginal samples.<br><br>CONCLUSIONS: Dysbiosis of the reproductive tract microbiota is associated with RPL and may represent a novel risk factor for pregnancy losses.}, }
@article {pmid35933808, year = {2022}, author = {Huang, J and Liu, W and Kang, W and He, Y and Yang, R and Mou, X and Zhao, W}, title = {Effects of microbiota on anticancer drugs: Current knowledge and potential applications.}, journal = {EBioMedicine}, volume = {83}, number = {}, pages = {104197}, pmid = {35933808}, issn = {2352-3964}, mesh = {*Antineoplastic Agents/pharmacology/therapeutic use ; Biomarkers ; Fecal Microbiota Transplantation ; Humans ; Immune Checkpoint Inhibitors ; *Microbiota ; *Probiotics/therapeutic use ; }, abstract = {Over the last decade, mounting evidence has revealed the key roles of gut microbiota in modulating the efficacy and toxicity of anticancer drugs, via mechanisms such as immunomodulation and microbial enzymatic degradation. As such, human microbiota presents as an exciting prospect for developing biomarkers for predicting treatment outcomes and interventional approaches for improving therapeutic effects. In this review, we analyze the current knowledge of the interplays among gut microorganisms, host responses and anticancer therapies (including cytotoxic chemotherapy and targeted therapy), with an emphasis on the immunomodulation function of microbiota which facilitates the efficacy of immune checkpoint inhibitors. Moreover, we propose several microbiota-modulating strategies including fecal microbiota transplantation and probiotics, which can be pursued to optimize the use and development of anticancer treatments. We anticipate that future clinical and preclinical studies will highlight the significance of human microbiome as a promising target towards precision medicine in cancer therapies. FUNDING: National Key Research and Development Program of China (2020YFA0907800), Shenzhen Science and Technology Innovation Program (KQTD20200820145822023) and National Natural Science Foundation of China (31900056 and 32000096).}, }
@article {pmid35933769, year = {2022}, author = {Morlock, GE and Morlock, JA and Cardak, AD and Mehl, A}, title = {Potential of simple, rapid, and non-target planar bioassay screening of veterinary drug residues.}, journal = {Journal of chromatography. A}, volume = {1679}, number = {}, pages = {463392}, doi = {10.1016/j.chroma.2022.463392}, pmid = {35933769}, issn = {1873-3778}, mesh = {Animals ; Anti-Bacterial Agents ; Biological Assay ; Chromatography, High Pressure Liquid ; *Drug Residues ; Fluoroquinolones ; Humans ; Milk ; *Veterinary Drugs ; }, abstract = {Veterinary drug residues in food samples of animal origin are currently analyzed by target analysis using high-performance liquid chromatography combined with sophisticated mass spectrometers. Since the results are only partially consistent with the microbiological results and positive findings occur rarely (in the per mil range in Germany), the potential of a simple planar bioassay screening was studied in the field of veterinary drug residue analysis. Using only a simple dilution of the milk for sample preparation, it was challenging to meet the maximum residue limits for antibiotic drug residues, exemplarily shown for the screening of two fluoroquinolones. However, the potential was evident for a simple, rapid, eco-friendly, and non-target screening without expensive instrumentation. Regardless of whether it is an active metabolite, contaminant, degradation product, or veterinary drug residue, the effect indicated on the planar surface due to bioassay detection will most likely also affect the human microbiome when consumed. The non-target screening of the milk samples revealed compounds with substantial antibacterial effects, which were not in the previous focus of interest. These antibacterial compounds will most likely also affect the human microbiome. Is it only the regulated antibiotic residues or generally all antibiotic compounds in a sample that count for consumer protection? The current prevailing understanding of food safety and antimicrobial resistance, based on the results of target (rather than effect) analyses, is being challenged. Non-target planar bioassay screening has been shown to fill a current gap by providing an understanding of inconsistencies and complementing routine target analysis of veterinary drug residues. As a highlight, it provides the full picture of the real levels of active compounds, regardless of the permitted limits of antibiotics.}, }
@article {pmid35931735, year = {2022}, author = {Kim, K and Lee, S and Park, SC and Kim, NE and Shin, C and Lee, SK and Jung, Y and Yoon, D and Kim, H and Kim, S and Hwang, GS and Won, S}, title = {Role of an unclassified Lachnospiraceae in the pathogenesis of type 2 diabetes: a longitudinal study of the urine microbiome and metabolites.}, journal = {Experimental &amp; molecular medicine}, volume = {54}, number = {8}, pages = {1125-1132}, pmid = {35931735}, issn = {2092-6413}, mesh = {Acetoacetates ; *Diabetes Mellitus, Type 2/complications ; Glycated Hemoglobin ; Humans ; Longitudinal Studies ; *Microbiota ; Prospective Studies ; }, abstract = {Recent investigations have revealed that the human microbiome plays an essential role in the occurrence of type 2 diabetes (T2D). However, despite the importance of understanding the involvement of the microbiota throughout the body in T2D, most studies have focused specifically on the intestinal microbiota. Extracellular vesicles (EVs) have been recently found to provide important evidence regarding the mechanisms of T2D pathogenesis, as they act as key messengers between intestinal microorganisms and the host. Herein, we explored microorganisms potentially associated with T2D by tracking changes in microbiota-derived EVs from patient urine samples collected three times over four years. Mendelian randomization analysis was conducted to evaluate the causal relationships among microbial organisms, metabolites, and clinical measurements to provide a comprehensive view of how microbiota can influence T2D. We also analyzed EV-derived metagenomic (N = 393), clinical (N = 5032), genomic (N = 8842), and metabolite (N = 574) data from a prospective longitudinal Korean community-based cohort. Our data revealed that GU174097_g, an unclassified Lachnospiraceae, was associated with T2D (β = -189.13; p = 0.00006), and it was associated with the ketone bodies acetoacetate and 3-hydroxybutyrate (r = -0.0938 and -0.0829, respectively; p = 0.0022 and 0.0069, respectively). Furthermore, a causal relationship was identified between acetoacetate and HbA1c levels (β = 0.0002; p = 0.0154). GU174097_g reduced ketone body levels, thus decreasing HbA1c levels and the risk of T2D. Taken together, our findings indicate that GU174097_g may lower the risk of T2D by reducing ketone body levels.}, }
@article {pmid35930417, year = {2022}, author = {Maybee, J and Pearson, T and Elliott, L}, title = {The Gut-Brain-Microbiome Connection: Can Probiotics Decrease Anxiety and Depression?.}, journal = {Issues in mental health nursing}, volume = {43}, number = {11}, pages = {996-1003}, doi = {10.1080/01612840.2022.2106525}, pmid = {35930417}, issn = {1096-4673}, mesh = {Humans ; Depression/drug therapy ; *Probiotics/therapeutic use ; Anxiety/therapy ; Brain ; *Microbiota ; }, abstract = {Anxiety and depression are highly prevalent mood disorders worldwide. Complete remission of symptoms is often difficult to achieve, despite following recommended treatment guidelines. Numerous antidepressants and anxiolytics exist, and new drugs are being developed constantly, yet the incidence of common mood disorders continues to rise. Despite the prevalence of these issues, mental health treatment has not evolved much in recent years. An exciting area of research uncovered in the past decade is the gut-brain-microbiome axis, a bi-directional communication pathway. Because the human microbiome is closely related to mood, research is being done to investigate whether probiotic supplementation could potentially affect symptoms of anxiety and depression.}, }
@article {pmid35928983, year = {2022}, author = {Hakimjavadi, H and George, SH and Taub, M and Dodds, LV and Sanchez-Covarrubias, AP and Huang, M and Pearson, JM and Slomovitz, BM and Kobetz, EN and Gharaibeh, R and Sowamber, R and Pinto, A and Chamala, S and Schlumbrecht, MP}, title = {The vaginal microbiome is associated with endometrial cancer grade and histology.}, journal = {Cancer research communications}, volume = {2}, number = {6}, pages = {447-455}, pmid = {35928983}, issn = {2767-9764}, support = {P30 CA240139/CA/NCI NIH HHS/United States ; }, mesh = {Humans ; Female ; *Endometrial Neoplasms/genetics ; Vagina/microbiology ; Hysterectomy ; *Microbiota/genetics ; *Carcinoma ; }, abstract = {The human microbiome has been strongly correlated with disease pathology and outcomes, yet remains relatively underexplored in patients with malignant endometrial disease. In this study, vaginal microbiome samples were prospectively collected at the time of hysterectomy from 61 racially and ethnically diverse patients from three disease conditions: 1) benign gynecologic disease (controls, n=11), 2) low-grade endometrial carcinoma (n=30), and 3) high-grade endometrial carcinoma (n=20). Extracted DNA underwent shotgun metagenomics sequencing, and microbial α and β diversities were calculated. Hierarchical clustering was used to describe community state types (CST), which were then compared by microbial diversity and grade. Differential abundance was calculated, and machine learning utilized to assess the predictive value of bacterial abundance to distinguish grade and histology. Both α- and β-diversity were associated with patient tumor grade. Four vaginal CST were identified that associated with grade of disease. Different histologies also demonstrated variation in CST within tumor grades. Using supervised clustering algorithms, critical microbiome markers at the species level were used to build models that predicted benign vs carcinoma, high-grade carcinoma versus benign, and high-grade versus low-grade carcinoma with high accuracy. These results confirm that the vaginal microbiome segregates not just benign disease from endometrial cancer, but is predictive of histology and grade. Further characterization of these findings in large, prospective studies is needed to elucidate their potential clinical applications.}, }
@article {pmid35928158, year = {2022}, author = {Díez López, C and Montiel González, D and Vidaki, A and Kayser, M}, title = {Prediction of Smoking Habits From Class-Imbalanced Saliva Microbiome Data Using Data Augmentation and Machine Learning.}, journal = {Frontiers in microbiology}, volume = {13}, number = {}, pages = {886201}, pmid = {35928158}, issn = {1664-302X}, abstract = {Human microbiome research is moving from characterization and association studies to translational applications in medical research, clinical diagnostics, and others. One of these applications is the prediction of human traits, where machine learning (ML) methods are often employed, but face practical challenges. Class imbalance in available microbiome data is one of the major problems, which, if unaccounted for, leads to spurious prediction accuracies and limits the classifier's generalization. Here, we investigated the predictability of smoking habits from class-imbalanced saliva microbiome data by combining data augmentation techniques to account for class imbalance with ML methods for prediction. We collected publicly available saliva 16S rRNA gene sequencing data and smoking habit metadata demonstrating a serious class imbalance problem, i.e., 175 current vs. 1,070 non-current smokers. Three data augmentation techniques (synthetic minority over-sampling technique, adaptive synthetic, and tree-based associative data augmentation) were applied together with seven ML methods: logistic regression, k-nearest neighbors, support vector machine with linear and radial kernels, decision trees, random forest, and extreme gradient boosting. K-fold nested cross-validation was used with the different augmented data types and baseline non-augmented data to validate the prediction outcome. Combining data augmentation with ML generally outperformed baseline methods in our dataset. The final prediction model combined tree-based associative data augmentation and support vector machine with linear kernel, and achieved a classification performance expressed as Matthews correlation coefficient of 0.36 and AUC of 0.81. Our method successfully addresses the problem of class imbalance in microbiome data for reliable prediction of smoking habits.}, }
@article {pmid35928143, year = {2022}, author = {Alves-Barroco, C and Brito, PH and Santos-Sanches, I and Fernandes, AR}, title = {Phylogenetic analysis and accessory genome diversity reveal insight into the evolutionary history of Streptococcus dysgalactiae.}, journal = {Frontiers in microbiology}, volume = {13}, number = {}, pages = {952110}, pmid = {35928143}, issn = {1664-302X}, abstract = {Streptococcus dysgalactiae (SD) is capable of infecting both humans and animals and causing a wide range of invasive and non-invasive infections. With two subspecies, the taxonomic status of subspecies of SD remains controversial. Subspecies equisimilis (SDSE) is an important human pathogen, while subspecies dysgalactiae (SDSD) has been considered a strictly animal pathogen; however, occasional human infections by this subspecies have been reported in the last few years. Moreover, the differences between the adaptation of SDSD within humans and other animals are still unknown. In this work, we provide a phylogenomic analysis based on the single-copy core genome of 106 isolates from both the subspecies and different infected hosts (animal and human hosts). The accessory genome of this species was also analyzed for screening of genes that could be specifically involved with adaptation to different hosts. Additionally, we searched putatively adaptive traits among prophage regions to infer the importance of transduction in the adaptation of SD to different hosts. Core genome phylogenetic relationships segregate all human SDSE in a single cluster separated from animal SD isolates. The subgroup of bovine SDSD evolved from this later clade and harbors a specialized accessory genome characterized by the presence of specific virulence determinants (e.g., cspZ) and carbohydrate metabolic functions (e.g., fructose operon). Together, our results indicate a host-specific SD and the existence of an SDSD group that causes human-animal cluster infections may be due to opportunistic infections, and that the exact incidence of SDSD human infections may be underestimated due to failures in identification based on the hemolytic patterns. However, more detailed research into the isolation of human SD is needed to assess whether it is a carrier phenomenon or whether the species can be permanently integrated into the human microbiome, making it ready to cause opportunistic infections.}, }
@article {pmid35913976, year = {2022}, author = {Gu, W and Moon, J and Chisina, C and Kang, B and Park, T and Koh, H}, title = {MiCloud: A unified web platform for comprehensive microbiome data analysis.}, journal = {PloS one}, volume = {17}, number = {8}, pages = {e0272354}, pmid = {35913976}, issn = {1932-6203}, mesh = {Cross-Sectional Studies ; Data Analysis ; *Gastrointestinal Microbiome/genetics ; High-Throughput Nucleotide Sequencing/methods ; Humans ; *Microbiota/genetics ; }, abstract = {The recent advance in massively parallel sequencing has enabled accurate microbiome profiling at a dramatically lowered cost. Then, the human microbiome has been the subject of intensive investigation in public health and medicine. In the meanwhile, researchers have developed lots of microbiome data analysis methods, protocols, and/or tools. Among those, especially, the web platforms can be highlighted because of the user-friendly interfaces and streamlined protocols for a long sequence of analytic procedures. However, existing web platforms can handle only a categorical trait of interest, cross-sectional study design, and the analysis with no covariate adjustment. We therefore introduce here a unified web platform, named MiCloud, for a binary or continuous trait of interest, cross-sectional or longitudinal/family-based study design, and with or without covariate adjustment. MiCloud handles all such types of analyses for both ecological measures (i.e., alpha and beta diversity indices) and microbial taxa in relative abundance on different taxonomic levels (i.e., phylum, class, order, family, genus and species). Importantly, MiCloud also provides a unified analytic protocol that streamlines data inputs, quality controls, data transformations, statistical methods and visualizations with vastly extended utility and flexibility that are suited to microbiome data analysis. We illustrate the use of MiCloud through the United Kingdom twin study on the association between gut microbiome and body mass index adjusting for age. MiCloud can be implemented on either the web server (http://micloud.kr) or the user's computer (https://github.com/wg99526/micloudgit).}, }
@article {pmid35899413, year = {2022}, author = {Steiner, HE and Patterson, HK and Giles, JB and Karnes, JH}, title = {Bringing pharmacomicrobiomics to the clinic through well-designed studies.}, journal = {Clinical and translational science}, volume = {15}, number = {10}, pages = {2303-2315}, pmid = {35899413}, issn = {1752-8062}, support = {R01 HL156993/HL/NHLBI NIH HHS/United States ; R01HL158686/HL/NHLBI NIH HHS/United States ; T32 ES007091/ES/NIEHS NIH HHS/United States ; R01 HL158686/HL/NHLBI NIH HHS/United States ; K01 HL143137/HL/NHLBI NIH HHS/United States ; K01HL143137/HL/NHLBI NIH HHS/United States ; }, mesh = {Humans ; *Drug-Related Side Effects and Adverse Reactions ; Gastrointestinal Microbiome/physiology ; *Microbiota ; Reproducibility of Results ; }, abstract = {Pharmacomicrobiomic studies investigate drug-microbiome interactions, such as the effect of microbial variation on drug response and disposition. Studying and understanding the interactions between the gut microbiome and drugs is becoming increasingly relevant to clinical practice due to its potential for avoiding adverse drug reactions or predicting variability in drug response. The highly variable nature of the human microbiome presents significant challenges to assessing microbes' influence. Studies aiming to explore drug-microbiome interactions should be well-designed to account for variation in the microbiome over time and collect data on confounders such as diet, disease, concomitant drugs, and other environmental factors. Here, we assemble a set of important considerations and recommendations for the methodological features required for performing a pharmacomicrobiomic study in humans with a focus on the gut microbiome. Consideration of these factors enable discovery, reproducibility, and more accurate characterization of the relationships between a given drug and the microbiome. Furthermore, appropriate interpretation and dissemination of results from well-designed studies will push the field closer to clinical relevance and implementation.}, }
@article {pmid35899309, year = {2022}, author = {Ye, P and Qiao, X and Tang, W and Wang, C and He, H}, title = {Testing latent class of subjects with structural zeros in negative binomial models with applications to gut microbiome data.}, journal = {Statistical methods in medical research}, volume = {31}, number = {11}, pages = {2237-2254}, doi = {10.1177/09622802221115881}, pmid = {35899309}, issn = {1477-0334}, mesh = {Humans ; *Gastrointestinal Microbiome ; Models, Statistical ; Computer Simulation ; Poisson Distribution ; }, abstract = {Human microbiome research has become a hot-spot in health and medical research in the past decade due to the rapid development of modern high-throughput. Typical data in a microbiome study consisting of the operational taxonomic unit counts may have over-dispersion and/or structural zero issues. In such cases, negative binomial models can be applied to address the over-dispersion issue, while zero-inflated negative binomial models can be applied to address both issues. In practice, it is essential to know if there is zero-inflation in the data before applying negative binomial or zero-inflated negative binomial models because zero-inflated negative binomial models may be unnecessarily complex and difficult to interpret, or may even suffer from convergence issues if there is no zero-inflation in the data. On the other hand, negative binomial models may yield invalid inferences if the data does exhibit excessive zeros. In this paper, we develop a new test for detecting zero-inflation resulting from a latent class of subjects with structural zeros in a negative binomial regression model by directly comparing the amount of observed zeros with what would be expected under the negative binomial regression model. A closed form of the test statistic as well as its asymptotic properties are derived based on estimating equations. Intensive simulation studies are conducted to investigate the performance of the new test and compare it with the classical Wald, likelihood ratio, and score tests. The tests are also applied to human gut microbiome data to test latent class in microbial genera.}, }
@article {pmid35889831, year = {2022}, author = {Sharon, I and Quijada, NM and Pasolli, E and Fabbrini, M and Vitali, F and Agamennone, V and Dötsch, A and Selberherr, E and Grau, JH and Meixner, M and Liere, K and Ercolini, D and de Filippo, C and Caderni, G and Brigidi, P and Turroni, S}, title = {The Core Human Microbiome: Does It Exist and How Can We Find It? A Critical Review of the Concept.}, journal = {Nutrients}, volume = {14}, number = {14}, pages = {}, pmid = {35889831}, issn = {2072-6643}, mesh = {Dysbiosis ; *Gastrointestinal Microbiome ; Humans ; Metagenomics/methods ; *Microbiota ; Sequence Analysis, DNA ; }, abstract = {The core microbiome, which refers to a set of consistent microbial features across populations, is of major interest in microbiome research and has been addressed by numerous studies. Understanding the core microbiome can help identify elements that lead to dysbiosis, and lead to treatments for microbiome-related health states. However, defining the core microbiome is a complex task at several levels. In this review, we consider the current state of core human microbiome research. We consider the knowledge that has been gained, the factors limiting our ability to achieve a reliable description of the core human microbiome, and the fields most likely to improve that ability. DNA sequencing technologies and the methods for analyzing metagenomics and amplicon data will most likely facilitate higher accuracy and resolution in describing the microbiome. However, more effort should be invested in characterizing the microbiome's interactions with its human host, including the immune system and nutrition. Other components of this holobiontic system should also be emphasized, such as fungi, protists, lower eukaryotes, viruses, and phages. Most importantly, a collaborative effort of experts in microbiology, nutrition, immunology, medicine, systems biology, bioinformatics, and machine learning is probably required to identify the traits of the core human microbiome.}, }
@article {pmid35888986, year = {2022}, author = {Rajakaruna, S and Pérez-Burillo, S and Kramer, DL and Rufián-Henares, J&#xc1; and Paliy, O}, title = {Dietary Melanoidins from Biscuits and Bread Crust Alter the Structure and Short-Chain Fatty Acid Production of Human Gut Microbiota.}, journal = {Microorganisms}, volume = {10}, number = {7}, pages = {}, pmid = {35888986}, issn = {2076-2607}, abstract = {Melanoidins are the products of the Maillard reaction between carbonyl and amino groups of macromolecules and are readily formed in foods, especially during heat treatment. In this study we utilized the three-stage Human Gut Simulator system to assess the effect of providing melanoidins extracted from either biscuits or bread crust to the human gut microbiota. Addition of melanoidins to the growth medium led to statistically significant alterations in the microbial community composition, and it increased short-chain fatty acid and antioxidant production by the microbiota. The magnitude of these changes was much higher for cultures grown with biscuit melanoidins. Several lines of evidence indicate that such differences between these melanoidin sources might be due to the presence of lipid components in biscuit melanoidin structures. Because melanoidins are largely not degraded by human gastrointestinal enzymes, they provide an additional source of microbiota-accessible nutrients to our gut microbes.}, }
@article {pmid35888025, year = {2022}, author = {Ratanapokasatit, Y and Laisuan, W and Rattananukrom, T and Petchlorlian, A and Thaipisuttikul, I and Sompornrattanaphan, M}, title = {How Microbiomes Affect Skin Aging: The Updated Evidence and Current Perspectives.}, journal = {Life (Basel, Switzerland)}, volume = {12}, number = {7}, pages = {}, pmid = {35888025}, issn = {2075-1729}, abstract = {The skin has a multifactorial aging process, caused by both intrinsic and extrinsic factors. A major theory of aging involves cellular senescence or apoptosis resulting from oxidative damage as the skin's antioxidant system tends to weaken with age. The human microbiota is a complex ecosystem that is made up of microorganisms (bacteria, fungi, and viruses). Both gut and skin microbiota have essential roles in the protection against invading pathogens, mediating inflammatory conditions, and the modulation of the immune system which is involved in both innate and adaptive immune responses. However, the human microbiome could be changed during the life stage and affected by various perturbations. An alteration of the intestinal bacteria results in "microbial dysbiosis" which is associated with the influence of various diseases, including aging. The skin interactome is a novel integration of the "genome-microbiome-exposome" that plays a significant role in skin aging and skin health. Mitigating the negative impacts of factors influencing the skin interactome should be the future strategy to protect, prevent, and delay skin aging along with preserving healthy skin conditions. This review summarizes the current evidence on how human microbiomes affect skin aging and demonstrates the possible interventions, relating to human microbiomes, to modulate skin health and aging. Probiotics-based products are currently available mainly for the add-on treatment of many dermatologic conditions. However, at this point, there are limited clinical studies on skin anti-aging purposes and more are required as this evolving concept is on the rise and might provide an insight into future therapeutic options.}, }
@article {pmid35886007, year = {2022}, author = {Hua, X and Song, L and Yu, G and Vogtmann, E and Goedert, JJ and Abnet, CC and Landi, MT and Shi, J}, title = {MicrobiomeGWAS: A Tool for Identifying Host Genetic Variants Associated with Microbiome Composition.}, journal = {Genes}, volume = {13}, number = {7}, pages = {}, pmid = {35886007}, issn = {2073-4425}, mesh = {*Genome-Wide Association Study ; Humans ; Lung ; *Microbiota/genetics ; Polymorphism, Single Nucleotide/genetics ; RNA, Ribosomal, 16S/genetics ; }, abstract = {The microbiome is the collection of all microbial genes and can be investigated by sequencing highly variable regions of 16S ribosomal RNA (rRNA) genes. Evidence suggests that environmental factors and host genetics may interact to impact human microbiome composition. Identifying host genetic variants associated with human microbiome composition not only provides clues for characterizing microbiome variation but also helps to elucidate biological mechanisms of genetic associations, prioritize genetic variants, and improve genetic risk prediction. Since a microbiota functions as a community, it is best characterized by β diversity; that is, a pairwise distance matrix. We develop a statistical framework and a computationally efficient software package, microbiomeGWAS, for identifying host genetic variants associated with microbiome β diversity with or without interacting with an environmental factor. We show that the score statistics have positive skewness and kurtosis due to the dependent nature of the pairwise data, which makes p-value approximations based on asymptotic distributions unacceptably liberal. By correcting for skewness and kurtosis, we develop accurate p-value approximations, whose accuracy was verified by extensive simulations. We exemplify our methods by analyzing a set of 147 genotyped subjects with 16S rRNA microbiome profiles from non-malignant lung tissues. Correcting for skewness and kurtosis eliminated the dramatic deviation in the quantile-quantile plots. We provided preliminary evidence that six established lung cancer risk SNPs were collectively associated with microbiome composition for both unweighted (p = 0.0032) and weighted (p = 0.011) UniFrac distance matrices. In summary, our methods will facilitate analyzing large-scale genome-wide association studies of the human microbiome.}, }
@article {pmid35885645, year = {2022}, author = {Hajjo, R and Sabbah, DA and Al Bawab, AQ}, title = {Unlocking the Potential of the Human Microbiome for Identifying Disease Diagnostic Biomarkers.}, journal = {Diagnostics (Basel, Switzerland)}, volume = {12}, number = {7}, pages = {}, pmid = {35885645}, issn = {2075-4418}, support = {2019-2020/23/07//Deanship of Scientific Research at Al-Zaytoonah University of Jordan/ ; }, abstract = {The human microbiome encodes more than three million genes, outnumbering human genes by more than 100 times, while microbial cells in the human microbiota outnumber human cells by 10 times. Thus, the human microbiota and related microbiome constitute a vast source for identifying disease biomarkers and therapeutic drug targets. Herein, we review the evidence backing the exploitation of the human microbiome for identifying diagnostic biomarkers for human disease. We describe the importance of the human microbiome in health and disease and detail the use of the human microbiome and microbiota metabolites as potential diagnostic biomarkers for multiple diseases, including cancer, as well as inflammatory, neurological, and metabolic diseases. Thus, the human microbiota has enormous potential to pave the road for a new era in biomarker research for diagnostic and therapeutic purposes. The scientific community needs to collaborate to overcome current challenges in microbiome research concerning the lack of standardization of research methods and the lack of understanding of causal relationships between microbiota and human disease.}, }
@article {pmid35883998, year = {2022}, author = {Inchingolo, AD and Malcangi, G and Semjonova, A and Inchingolo, AM and Patano, A and Coloccia, G and Ceci, S and Marinelli, G and Di Pede, C and Ciocia, AM and Mancini, A and Palmieri, G and Barile, G and Settanni, V and De Leonardis, N and Rapone, B and Piras, F and Viapiano, F and Cardarelli, F and Nucci, L and Bordea, IR and Scarano, A and Lorusso, F and Palermo, A and Costa, S and Tartaglia, GM and Corriero, A and Brienza, N and Di Venere, D and Inchingolo, F and Dipalma, G}, title = {Oralbiotica/Oralbiotics: The Impact of Oral Microbiota on Dental Health and Demineralization: A Systematic Review of the Literature.}, journal = {Children (Basel, Switzerland)}, volume = {9}, number = {7}, pages = {}, pmid = {35883998}, issn = {2227-9067}, abstract = {The oral microbiota plays a vital role in the human microbiome and oral health. Imbalances between microbes and their hosts can lead to oral and systemic disorders such as diabetes or cardiovascular disease. The purpose of this review is to investigate the literature evidence of oral microbiota dysbiosis on oral health and discuss current knowledge and emerging mechanisms governing oral polymicrobial synergy and dysbiosis; both have enhanced our understanding of pathogenic mechanisms and aided the design of innovative therapeutic approaches as ORALBIOTICA for oral diseases such as demineralization. PubMed, Web of Science, Google Scholar, Scopus, Cochrane Library, EMBEDDED, Dentistry &amp; Oral Sciences Source via EBSCO, APA PsycINFO, APA PsyArticles, and DRUGS@FDA were searched for publications that matched our topic from January 2017 to 22 April 2022, with an English language constraint using the following Boolean keywords: ("microbio*" and "demineralization*") AND ("oral microbiota" and "demineralization"). Twenty-two studies were included for qualitative analysis. As seen by the studies included in this review, the balance of the microbiota is unstable and influenced by oral hygiene, the presence of orthodontic devices in the oral cavity and poor eating habits that can modify its composition and behavior in both positive and negative ways, increasing the development of demineralization, caries processes, and periodontal disease. Under conditions of dysbiosis, favored by an acidic environment, the reproduction of specific bacterial strains increases, favoring cariogenic ones such as Bifidobacterium dentium, Bifidobacterium longum, and S. mutans, than S. salivarius and A. viscosus, and increasing of Firmicutes strains to the disadvantage of Bacteroidetes. Microbial balance can be restored by using probiotics and prebiotics to manage and treat oral diseases, as evidenced by mouthwashes or dietary modifications that can influence microbiota balance and prevent or slow disease progression.}, }
@article {pmid35877336, year = {2022}, author = {Lai, Y and Mi, J and Feng, Q}, title = {Fusobacterium nucleatum and Malignant Tumors of the Digestive Tract: A Mechanistic Overview.}, journal = {Bioengineering (Basel, Switzerland)}, volume = {9}, number = {7}, pages = {}, pmid = {35877336}, issn = {2306-5354}, support = {ZR2021MC098//Natural Science Foundation of Shandong Province/ ; }, abstract = {Fusobacterium nucleatum (F. nucleatum) is an oral anaerobe that plays a role in several oral diseases. However, F. nucleatum is also found in other tissues of the digestive tract, and several studies have recently reported that the level of F. nucleatum is significantly elevated in malignant tumors of the digestive tract. F. nucleatum is proposed as one of the risk factors in the initiation and progression of digestive tract malignant tumors. In this review, we summarize recent reports on F. nucleatum and its role in digestive tract cancers and evaluate the mechanisms underlying the action of F. nucleatum in digestive tract cancers.}, }
@article {pmid35876529, year = {2022}, author = {Kitrinos, C and Bell, RB and Bradley, BJ and Kamilar, JM}, title = {Hair Microbiome Diversity within and across Primate Species.}, journal = {mSystems}, volume = {7}, number = {4}, pages = {e0047822}, pmid = {35876529}, issn = {2379-5077}, mesh = {Animals ; Humans ; *Gastrointestinal Microbiome ; Phylogeny ; Primates ; *Microbiota/genetics ; Hair ; }, abstract = {Primate hair and skin are substrates upon which social interactions occur and are host-pathogen interfaces. While human hair and skin microbiomes display body site specificity and immunological significance, little is known about the nonhuman primate (NHP) hair microbiome. Here, we collected hair samples (n = 158) from 8 body sites across 12 NHP species housed at three zoological institutions in the United States to examine the following: (1) the diversity and composition of the primate hair microbiome and (2) the factors predicting primate hair microbiome diversity and composition. If both environmental and evolutionary factors shape the microbiome, then we expect significant differences in microbiome diversity across host body sites, sexes, institutions, and species. We found our samples contained high abundances of gut-, respiratory-, and environment-associated microbiota. In addition, multiple factors predicted microbiome diversity and composition, although host species identity outweighed sex, body site, and institution as the strongest predictor. Our results suggest that hair microbial communities are affected by both evolutionary and environmental factors and are relatively similar across nonhuman primate body sites, which differs from the human condition. These findings have important implications for understanding the biology and conservation of wild and captive primates and the uniqueness of the human microbiome. IMPORTANCE We created the most comprehensive primate hair and skin data set to date, including data from 12 nonhuman primate species sampled from 8 body regions each. We find that the nonhuman primate hair microbiome is distinct from the human hair and skin microbiomes in that it is relatively uniform-as opposed to distinct-across body regions and is most abundant in gut-, environment-, and respiratory-associated microbiota rather than human skin-associated microbiota. Furthermore, we found that the nonhuman primate hair microbiome varies with host species identity, host sex, host environment, and host body site, with host species identity being the strongest predictor. This result demonstrates that nonhuman primate hair microbiome diversity varies with both evolutionary and environmental factors and within and across primate species. These findings have important implications for understanding the biology and conservation of wild and captive primates and the uniqueness of the human microbiome.}, }
@article {pmid35875231, year = {2022}, author = {Stuivenberg, G and Daisley, B and Akouris, P and Reid, G}, title = {In vitro assessment of histamine and lactate production by a multi-strain synbiotic.}, journal = {Journal of food science and technology}, volume = {59}, number = {9}, pages = {3419-3427}, pmid = {35875231}, issn = {0022-1155}, abstract = {Recent studies suggest histamine and d-lactate may negatively impact host health. As excess histamine is deleterious to the host, the identification of bacterial producers has contributed to concerns over the consumption of probiotics or live microorganisms in fermented food items. Some probiotic products have been suspected of inducing d-lactic-acidosis; an illness associated with neurocognitive symptoms such as ataxia. The goals of the present study were to test the in vitro production of histamine and d-lactate by a 24-strain daily synbiotic and to outline methods that others can use to test for their production. Using enzymatic based assays, no significant production of histamine was observed compared to controls (P > 0.05), while d-lactate production was comparable to a commercially available probiotic with no associated health risk. These assays provide a means to add to the safety profile of synbiotic and probiotic products.}, }
@article {pmid35873161, year = {2022}, author = {Romani, L and Del Chierico, F and Macari, G and Pane, S and Ristori, MV and Guarrasi, V and Gardini, S and Pascucci, GR and Cotugno, N and Perno, CF and Rossi, P and Villani, A and Bernardi, S and Campana, A and Palma, P and Putignani, L and , }, title = {The Relationship Between Pediatric Gut Microbiota and SARS-CoV-2 Infection.}, journal = {Frontiers in cellular and infection microbiology}, volume = {12}, number = {}, pages = {908492}, pmid = {35873161}, issn = {2235-2988}, mesh = {Adult ; Bacteroides/genetics ; Bifidobacterium/genetics ; *COVID-19/complications ; Child ; Clostridium/genetics ; Feces/microbiology ; *Gastrointestinal Microbiome/physiology ; Humans ; RNA, Ribosomal, 16S/genetics ; SARS-CoV-2 ; Systemic Inflammatory Response Syndrome ; }, abstract = {This is the first study on gut microbiota (GM) in children affected by coronavirus disease 2019 (COVID-19). Stool samples from 88 patients with suspected severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and 95 healthy subjects were collected (admission: 3-7 days, discharge) to study GM profile by 16S rRNA gene sequencing and relationship to disease severity. The study group was divided in COVID-19 (68), Non-COVID-19 (16), and MIS-C (multisystem inflammatory syndrome in children) (4). Correlations among GM ecology, predicted functions, multiple machine learning (ML) models, and inflammatory response were provided for COVID-19 and Non-COVID-19 cohorts. The GM of COVID-19 cohort resulted as dysbiotic, with the lowest α-diversity compared with Non-COVID-19 and CTRLs and by a specific β-diversity. Its profile appeared enriched in Faecalibacterium, Fusobacterium, and Neisseria and reduced in Bifidobacterium, Blautia, Ruminococcus, Collinsella, Coprococcus, Eggerthella, and Akkermansia, compared with CTRLs (p < 0.05). All GM paired-comparisons disclosed comparable results through all time points. The comparison between COVID-19 and Non-COVID-19 cohorts highlighted a reduction of Abiotrophia in the COVID-19 cohort (p < 0.05). The GM of MIS-C cohort was characterized by an increase of Veillonella, Clostridium, Dialister, Ruminococcus, and Streptococcus and a decrease of Bifidobacterium, Blautia, Granulicatella, and Prevotella, compared with CTRLs. Stratifying for disease severity, the GM associated to "moderate" COVID-19 was characterized by lower α-diversity compared with "mild" and "asymptomatic" and by a GM profile deprived in Neisseria, Lachnospira, Streptococcus, and Prevotella and enriched in Dialister, Acidaminococcus, Oscillospora, Ruminococcus, Clostridium, Alistipes, and Bacteroides. The ML models identified Staphylococcus, Anaerostipes, Faecalibacterium, Dorea, Dialister, Streptococcus, Roseburia, Haemophilus, Granulicatella, Gemmiger, Lachnospira, Corynebacterium, Prevotella, Bilophila, Phascolarctobacterium, Oscillospira, and Veillonella as microbial markers of COVID-19. The KEGG ortholog (KO)-based prediction of GM functional profile highlighted 28 and 39 KO-associated pathways to COVID-19 and CTRLs, respectively. Finally, Bacteroides and Sutterella correlated with proinflammatory cytokines regardless disease severity. Unlike adult GM profiles, Faecalibacterium was a specific marker of pediatric COVID-19 GM. The durable modification of patients' GM profile suggested a prompt GM quenching response to SARS-CoV-2 infection since the first symptoms. Faecalibacterium and reduced fatty acid and amino acid degradation were proposed as specific COVID-19 disease traits, possibly associated to restrained severity of SARS-CoV-2-infected children. Altogether, this evidence provides a characterization of the pediatric COVID-19-related GM.}, }
@article {pmid35872253, year = {2022}, author = {Kantele, A and Mero, S and Lääveri, T}, title = {Doxycycline as an antimalarial: Impact on travellers' diarrhoea and doxycycline resistance among various stool bacteria - Prospective study and literature review.}, journal = {Travel medicine and infectious disease}, volume = {49}, number = {}, pages = {102403}, doi = {10.1016/j.tmaid.2022.102403}, pmid = {35872253}, issn = {1873-0442}, mesh = {Anti-Bacterial Agents/pharmacology/therapeutic use ; *Antimalarials/pharmacology/therapeutic use ; Bacteria ; Diarrhea/drug therapy/microbiology ; Doxycycline/pharmacology/therapeutic use ; Enterobacteriaceae ; *Enterobacteriaceae Infections/microbiology ; Humans ; Prospective Studies ; Travel ; Travel-Related Illness ; beta-Lactamases ; }, abstract = {BACKGROUND: Antibiotics predispose travellers to acquire multidrug-resistant bacteria, such as extended-spectrum beta-lactamase-producing Enterobacterales (ESBL-PE). Although widely used in antimalarial prophylaxis, doxycycline has scarcely been studied in this respect.<br><br>METHODS: We explored the impact of doxycycline on rates of traveller's diarrhoea (TD), ESBL-PE acquisition and, particularly, doxycycline co-resistance among travel-acquired ESBL-PE in a sample of 412 visitors to low- and middle-income countries. We reviewed the literature on traveller studies of doxycycline/tetracycline resistance among stool pathogens and the impact of doxycycline on TD rates, ESBL-PE acquisition, and doxycycline/tetracycline resistance.<br><br>RESULTS: The TD rates were similar for doxycycline users (32/46; 69.6%) and non-users (256/366; 69.9%). Of the 90 travel-acquired ESBL-PE isolates, 84.4% were co-resistant to doxycycline: 100% (11/11) among users and 82.3% (65/79) among non-users. The literature on doxycycline's effect on TD was not conclusive nor did it support a recent decline in doxycycline resistance. Although doxycycline did not increase ESBL-PE acquisition, doxycycline-resistance among stool pathogens proved more frequent for users than non-users.<br><br>CONCLUSIONS: Our prospective data and the literature review together suggest the following: 1) doxycycline does not prevent TD; 2) doxycycline use favours acquisition of doxy/tetracycline-co-resistant intestinal bacteria; 3) although doxycycline does not predispose to travel-related ESBL-PE acquisition per se, it selects ESBL-PE strains co-resistant to doxycycline; 4) doxycycline resistance rates are high among stool bacteria in general with no evidence of any tendency to decrease.}, }
@article {pmid35869172, year = {2022}, author = {Maarsingh, JD and Łaniewski, P and Herbst-Kralovetz, MM}, title = {Immunometabolic and potential tumor-promoting changes in 3D cervical cell models infected with bacterial vaginosis-associated bacteria.}, journal = {Communications biology}, volume = {5}, number = {1}, pages = {725}, pmid = {35869172}, issn = {2399-3642}, support = {3P30CA023074-39S3//Division of Cancer Prevention, National Cancer Institute (NCI Division of Cancer Prevention)/ ; }, mesh = {Bacteria/*classification/pathogenicity ; Cervix Uteri/cytology/*microbiology ; Female ; Humans ; *Microbiota ; Tumor Microenvironment ; Uterine Cervical Neoplasms/*etiology/microbiology ; Vaginosis, Bacterial/complications/immunology/metabolism/*microbiology ; }, abstract = {Specific bacteria of the human microbiome influence carcinogenesis at diverse anatomical sites. Bacterial vaginosis (BV) is the most common vaginal disorder in premenopausal women that is associated with gynecologic sequelae, including cervical cancer. BV-associated microorganisms, such as Fusobacterium, Lancefieldella, Peptoniphilus, and Porphyromonas have been associated with gynecologic and other cancers, though the pro-oncogenic mechanisms employed by these bacteria are poorly understood. Here, we integrated a multi-omics approach with our three-dimensional (3-D) cervical epithelial cell culture model to investigate how understudied BV-associated bacteria linked to gynecologic neoplasia influence hallmarks of cancer in vitro. Lancefieldella parvulum and Peptoniphilus lacrimalis elicited robust proinflammatory responses in 3-D cervical cells. Fusobacterium nucleatum and Fusobacterium gonidiaformans modulated metabolic hallmarks of cancer corresponding to accumulation of 2-hydroxyglutarate, pro-inflammatory lipids, and signs of oxidative stress and genotoxic hydrogen sulfide. This study provides mechanistic insights into how gynecologic cancer-associated bacteria might facilitate a tumor-promoting microenvironment in the human cervix.}, }
@article {pmid35868276, year = {2022}, author = {Lloréns-Rico, V and Simcock, JA and Huys, GRB and Raes, J}, title = {Single-cell approaches in human microbiome research.}, journal = {Cell}, volume = {185}, number = {15}, pages = {2725-2738}, doi = {10.1016/j.cell.2022.06.040}, pmid = {35868276}, issn = {1097-4172}, mesh = {Bacteria/genetics ; Genome, Microbial ; Host Microbial Interactions ; Humans ; *Microbiota ; Sequence Analysis, RNA ; Single-Cell Analysis ; }, abstract = {Microbial culturing and meta-omic profiling technologies have significantly advanced our understanding of the taxonomic and functional variation of the human microbiome and its impact on host processes. The next increase in resolution will come by understanding the role of low-abundant and less-prevalent bacteria and the study of individual cell behaviors that underlie the complexity of microbial ecosystems. To this aim, single-cell techniques are being rapidly developed to isolate, culture, and characterize the genomes and transcriptomes of individual microbes in complex communities. Here, we discuss how these single-cell technologies are providing unique insights into the biology and behavior of human microbiomes.}, }
@article {pmid35863030, year = {2022}, author = {Rhoades, NS and Cinco, IR and Hendrickson, SM and Slifka, MK and Messaoudi, I}, title = {Taxonomic and Functional Shifts in the Perinatal Gut Microbiome of Rhesus Macaques.}, journal = {Microbiology spectrum}, volume = {10}, number = {4}, pages = {e0081422}, pmid = {35863030}, issn = {2165-0497}, support = {P51 OD011092/OD/NIH HHS/United States ; }, mesh = {Adult ; Animals ; Butyrates ; Feces ; Female ; Folic Acid ; *Gastrointestinal Microbiome/physiology ; Humans ; Infant, Newborn ; Macaca mulatta/genetics/metabolism ; Pregnancy ; RNA, Ribosomal, 16S/genetics ; Starch ; }, abstract = {Pregnancy and the postpartum period result in some of the most dramatic metabolic, hormonal, and physiological changes that can be experienced by an otherwise healthy adult. The timing and magnitude of these changes is key for both maternal and fetal health. One of the factors believed to critically modulate these physiological changes is the maternal gut microbiome. However, the dynamic changes in this community during the perinatal period remain understudied. Clinical studies can be complicated by confounding variables like diet and other drivers of heterogeneity in the human microbiome. Therefore, in this study, we conducted a longitudinal analysis of the fecal microbiome obtained during the pregnancy and postpartum periods in 26 captive rhesus macaques using 16S rRNA gene amplicon sequencing and shotgun metagenomics. Shifts at both the taxonomic and functional potential level were detected when comparing pregnancy to postpartum samples. Taxonomically, Alloprevotella, Actinobacillus, and Anaerovibrio were enriched in the gut microbiome during pregnancy, while Treponema, Lachnospiraceae, and Methanosphaera were more abundant postpartum. Functionally, the gut microbiome during pregnancy was associated with increased abundance in pathways involving the production of the short-chain fatty acid (SCFA) butyrate, while pathways associated with starch degradation and folate transformation were more abundant during the postpartum period. These data demonstrate dramatic changes in the maternal gut microbiome even in the absence of dietary changes and suggest that rhesus macaques could provide a valuable model to determine how changes in the microbiome correlate to other physiological changes in pregnancy. IMPORTANCE Pregnancy and the postpartum period are characterized by a myriad of metabolic and physiological adaptations needed to support fetal growth and maternal health. The maternal gut microbiome is believed to play a key role during this period but remains underexplored. Here, we report significant shifts in the taxonomic landscape and functional potential of the gut microbiome in 26 pregnant rhesus macaques during the transition from pregnancy to the postpartum period, despite shared dietary and environmental exposures. Increased abundance of pathways involved in the production of the short-chain fatty acid butyrate could play a critical role in modulating the maternal immune system and regulating fetal tolerance. On the other hand, increased abundance of pathways associated with starch degradation and folate transformation during the postpartum period could be important for meeting the metabolic demands of breastfeeding and neonatal growth.}, }
@article {pmid35863001, year = {2022}, author = {Khan, MT and Mahmud, A and Hasan, M and Azim, KF and Begum, MK and Rolin, MH and Akter, A and Mondal, SI}, title = {Proteome Exploration of Legionella pneumophila To Identify Novel Therapeutics: a Hierarchical Subtractive Genomics and Reverse Vaccinology Approach.}, journal = {Microbiology spectrum}, volume = {10}, number = {4}, pages = {e0037322}, pmid = {35863001}, issn = {2165-0497}, mesh = {Anti-Bacterial Agents ; Epitopes ; Genomics ; Humans ; *Legionella pneumophila/genetics ; *Legionnaires' Disease/drug therapy/prevention &amp; control ; Molecular Docking Simulation ; *Proteome ; Toll-Like Receptor 2 ; Vaccinology ; }, abstract = {Legionella pneumophila is the causative agent of a severe type of pneumonia (lung infection) called Legionnaires' disease. It is emerging as an antibiotic-resistant strain day by day. Hence, identifying novel drug targets and vaccine candidates is essential to fight against this pathogen. Here, attempts were taken through a subtractive genomics approach on the complete proteome of L. pneumophila to address the challenges of multidrug resistance. A total of 2,930 proteins from L. pneumophila proteome were investigated through diverse subtractive proteomics approaches, e.g., identification of human nonhomologous and pathogen-specific essential proteins, druggability and "anti-target" analysis, subcellular localization prediction, human microbiome nonhomology screening, and protein-protein interaction studies to find out effective drug and vaccine targets. Only three fulfilled these criteria and were proposed as novel drug targets against L. pneumophila. Furthermore, outer membrane protein TolB was identified as a potential vaccine target with a better antigenicity score. Antigenicity and transmembrane topology screening, allergenicity and toxicity assessment, population coverage analysis, and a molecular docking approach were adopted to generate the most potent epitopes. The final vaccine was constructed by the combination of highly immunogenic epitopes, along with suitable adjuvant and linkers. The designed vaccine construct showed higher binding interaction with different major histocompatibility complex (MHC) molecules and human immune TLR-2 receptors with minimum deformability at the molecular level. The present study aids the development of novel therapeutics and vaccine candidates for efficient treatment and prevention of L. pneumophila infections. However, further wet-lab-based phenotypic and genomic investigations and in vivo trials are highly recommended to validate our prediction experimentally. IMPORTANCE Legionella pneumophila is a human pathogen distributed worldwide, causing Legionnaires' disease (LD), a severe form of pneumonia and respiratory tract infection. L. pneumophila is emerging as an antibiotic-resistant strain, and controlling LD is now difficult. Hence, developing novel drugs and vaccines against L. pneumophila is a major research priority. Here, the complete proteome of L. pneumophila was considered for subtractive genomics approaches to address the challenge of antimicrobial resistance. Our subtractive proteomics approach identified three potential drug targets that are promising for future application. Furthermore, a possible vaccine candidate, "outer membrane protein TolB," was proposed using reverse vaccinology analysis. The constructed vaccine candidate showed higher binding interaction with MHC molecules and human immune TLR-2 receptors at the molecular level. Overall, the present study aids in developing novel therapeutics and vaccine candidates for efficient treatment of the infections caused by L. pneumophila.}, }
@article {pmid35861908, year = {2022}, author = {Fabbrocini, G and Ferrillo, M and Donnarumma, M and Papale, A and Pinto, D and Rinaldi, F}, title = {A Randomized, Double-Blind, Placebo-Controlled, Multicentric Study to Evaluate the Efficacy and the Tolerability of a Class II Medical Device in the Treatment of Mild and Moderate Acne.}, journal = {Dermatology and therapy}, volume = {12}, number = {8}, pages = {1835-1845}, pmid = {35861908}, issn = {2193-8210}, abstract = {INTRODUCTION: Several options are available to treat acne lesions, including topical benzoyl peroxide, topical retinoids, topical antibiotics, oral antibiotics, hormonal therapy, isotretinoin, and procedural therapies, such as light and laser therapies, although these cause side effects. This study aimed to establish the efficacy and tolerability of a class IIa medical device containing lactic acid, azelaic acid/polyglyceryl-3 copolymer, azelamidopropyl dimethyl amine, and bifida ferment lysate for the treatment of mild and moderate acne lesions.<br><br>METHODS: A randomized, double-blind, placebo-controlled, multicentric study was carried out in which 60 persons of both genders aged&#x2009;&#x2265;&#x2009;16&#xa0;years affected by mild or moderate acne were enrolled. Each person used the product twice daily for 2&#xa0;months. The clinical score (classified as absent, mild, moderate, and severe) of lesions such as blackheads, whiteheads, papules and pustules, erythema, desquamation, sebum secretion, and porphyrins production by a wood lamp was evaluated on the basis of a dermatologist's visual assessment at baseline (t0) and after 2&#xa0;months of treatment (t1), and the results were compared between groups. Digital photographic images were also taken.<br><br>RESULTS: Sixty subjects concluded the trial. It was observed that subjects treated with the medical device (group I) showed overall improvement in the analyzed acne lesions compared with placebo (group II) after 2&#xa0;months of treatment. The efficacy of the treatment was also expressed as partial and total clearance. The medical device produced higher percentages of both partial and total clearance in all analyzed parameters, compared with the placebo group. The study was safe and well tolerated.<br><br>CONCLUSIONS: It was observed that the participants showed an overall improvement of the analyzed lesions in comparison with the placebo group, without adverse events during the trial. Hence, the medical device was found to be safe and effective in the treatment of mild or moderate acne.}, }
@article {pmid35856563, year = {2022}, author = {Lesniak, NA and Schubert, AM and Flynn, KJ and Leslie, JL and Sinani, H and Bergin, IL and Young, VB and Schloss, PD}, title = {The Gut Bacterial Community Potentiates Clostridioides difficile Infection Severity.}, journal = {mBio}, volume = {13}, number = {4}, pages = {e0118322}, pmid = {35856563}, issn = {2150-7511}, support = {T32 AI007528/AI/NIAID NIH HHS/United States ; U19 AI090871/AI/NIAID NIH HHS/United States ; R01 GM099514/GM/NIGMS NIH HHS/United States ; P30 DK034933/DK/NIDDK NIH HHS/United States ; U2C DK110768/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Bacteria/genetics ; Bile Acids and Salts ; *Clostridioides difficile ; *Clostridium Infections/microbiology ; Feces/microbiology ; *Gastrointestinal Microbiome ; Humans ; Mice ; }, abstract = {The severity of Clostridioides difficile infections (CDI) has increased over the last few decades. Patient age, white blood cell count, and creatinine levels as well as C. difficile ribotype and toxin genes have been associated with disease severity. However, it is unclear whether specific members of the gut microbiota are associated with variations in disease severity. The gut microbiota is known to interact with C. difficile during infection. Perturbations to the gut microbiota are necessary for C. difficile to colonize the gut. The gut microbiota can inhibit C. difficile colonization through bile acid metabolism, nutrient consumption, and bacteriocin production. Here, we sought to demonstrate that members of the gut bacterial communities can also contribute to disease severity. We derived diverse gut communities by colonizing germfree mice with different human fecal communities. The mice were then infected with a single C. difficile ribotype 027 clinical isolate, which resulted in moribundity and histopathologic differences. The variation in severity was associated with the human fecal community that the mice received. Generally, bacterial populations with pathogenic potential, such as Enterococcus, Helicobacter, and Klebsiella, were associated with more-severe outcomes. Bacterial groups associated with fiber degradation and bile acid metabolism, such as Anaerotignum, Blautia, Lactonifactor, and Monoglobus, were associated with less-severe outcomes. These data indicate that, in addition to the host and C. difficile subtype, populations of gut bacteria can influence CDI disease severity. IMPORTANCE Clostridioides difficile colonization can be asymptomatic or develop into an infection ranging in severity from mild diarrhea to toxic megacolon, sepsis, and death. Models that predict severity and guide treatment decisions are based on clinical factors and C. difficile characteristics. Although the gut microbiome plays a role in protecting against CDI, its effect on CDI disease severity is unclear and has not been incorporated into disease severity models. We demonstrated that variation in the microbiome of mice colonized with human feces yielded a range of disease outcomes. These results revealed groups of bacteria associated with both severe and mild C. difficile infection outcomes. Gut bacterial community data from patients with CDI could improve our ability to identify patients at risk of developing more severe disease and improve interventions that target C. difficile and the gut bacteria to reduce host damage.}, }
@article {pmid35838756, year = {2022}, author = {Ksiezarek, M and Grosso, F and Ribeiro, TG and Peixe, L}, title = {Genomic diversity of genus Limosilactobacillus.}, journal = {Microbial genomics}, volume = {8}, number = {7}, pages = {}, pmid = {35838756}, issn = {2057-5858}, mesh = {*Genome ; *Genomics ; Lactobacillaceae ; }, abstract = {The genus Limosilactobacillus (formerly Lactobacillus) contains multiple species considered to be adapted to vertebrates, yet their genomic diversity has not been explored. In this study, we performed comparative genomic analysis of Limosilactobacillus (22 species; 332 genomes) isolated from different niches, further focusing on human strains (11 species; 74 genomes) and their adaptation features to specific body sites. Phylogenomic analysis of Limosilactobacillus showed misidentification of some strains deposited in public databases and existence of putative novel Limosilactobacillus species. The pangenome analysis revealed a remarkable genomic diversity (only 1.3 % of gene clusters are shared), and we did not observe a strong association of the accessory genome with different niches. The pangenome of Limosilactobacillus reuteri and Limosilactobacillus fermentum was open, suggesting that acquisition of genes is still occurring. Although most Limosilactobacillus were predicted as antibiotic susceptible (83%), acquired antibiotic-resistance genes were common in L. reuteri from food-producing animals. Genes related to lactic acid isoform production (>95 %) and putative bacteriocins (70.2%) were identified in most Limosilactobacillus strains, while prophages (55.4%) and CRISPR-Cas systems (32.0%) were less prevalent. Among strains from human sources, several metabolic pathways were predicted as conserved and completed. Their accessory genome was highly variable and did not cluster according to different human body sites, with some exceptions (urogenital Limosilactobacillus vaginalis , Limosilactobacillus portuensis , Limosilactobacillus urinaemulieris and Limosilactobacillus coleohominis or gastrointestinal Limosilactobacillus mucosae). Moreover, we identified 12 Kyoto Encyclopedia of Genes and Genomes (KEGG) orthologues that were significantly enriched in strains from particular body sites. We concluded that evolution of the highly diverse Limosilactobacillus is complex and not always related to niche or human body site origin.}, }
@article {pmid35835996, year = {2022}, author = {Merli, P and Massa, M and Russo, A and Rea, F and Del Chierico, F and Galaverna, F and Del Bufalo, F and Pane, S and Algeri, M and Romeo, EF and Masucci, L and De Angelis, P and Putignani, L and Locatelli, F}, title = {Fecal microbiota transplantation for the treatment of steroid-refractory, intestinal, graft-versus-host disease in a pediatric patient.}, journal = {Bone marrow transplantation}, volume = {57}, number = {10}, pages = {1600-1603}, pmid = {35835996}, issn = {1476-5365}, mesh = {Child ; Fecal Microbiota Transplantation ; *Graft vs Host Disease/therapy ; *Hematopoietic Stem Cell Transplantation ; Humans ; Steroids ; }, }
@article {pmid35832621, year = {2022}, author = {Balaji, A and Sapoval, N and Seto, C and Leo Elworth, RA and Fu, Y and Nute, MG and Savidge, T and Segarra, S and Treangen, TJ}, title = {KOMB: K-core based de novo characterization of copy number variation in microbiomes.}, journal = {Computational and structural biotechnology journal}, volume = {20}, number = {}, pages = {3208-3222}, pmid = {35832621}, issn = {2001-0370}, support = {U01 AI124290/AI/NIAID NIH HHS/United States ; }, abstract = {Characterizing metagenomes via kmer-based, database-dependent taxonomic classification has yielded key insights into underlying microbiome dynamics. However, novel approaches are needed to track community dynamics and genomic flux within metagenomes, particularly in response to perturbations. We describe KOMB, a novel method for tracking genome level dynamics within microbiomes. KOMB utilizes K-core decomposition to identify Structural variations (SVs), specifically, population-level Copy Number Variation (CNV) within microbiomes. K-core decomposition partitions the graph into shells containing nodes of induced degree at least K, yielding reduced computational complexity compared to prior approaches. Through validation on a synthetic community, we show that KOMB recovers and profiles repetitive genomic regions in the sample. KOMB is shown to identify functionally-important regions in Human Microbiome Project datasets, and was used to analyze longitudinal data and identify keystone taxa in Fecal Microbiota Transplantation (FMT) samples. In summary, KOMB represents a novel graph-based, taxonomy-oblivious, and reference-free approach for tracking CNV within microbiomes. KOMB is open source and available for download at https://gitlab.com/treangenlab/komb.}, }
@article {pmid35814671, year = {2022}, author = {Vacca, M and Porrelli, A and Calabrese, FM and Lippolis, T and Iacobellis, I and Celano, G and Pinto, D and Russo, F and Giannelli, G and De Angelis, M}, title = {How Metabolomics Provides Novel Insights on Celiac Disease and Gluten-Free Diet: A Narrative Review.}, journal = {Frontiers in microbiology}, volume = {13}, number = {}, pages = {859467}, pmid = {35814671}, issn = {1664-302X}, abstract = {Celiac disease (CD) is an inflammatory autoimmune disorder triggered by the ingestion of gluten from wheat and other cereals. Nowadays, its positive diagnosis is based on invasive approaches such as the histological examination of intestinal biopsies and positive serology screening of antibodies. After proven diagnosis, the only admissible treatment for CD individuals is strict life-long adherence to gluten-free diet (GFD), although it is not a conclusive therapy. Acting by different mechanisms and with different etiologies, both CD and GFD have a great impact on gut microbiota that result in a different taxa composition. Altered production of specific metabolites reflects these microbiota changes. In this light, the currently available literature reports some suggestions about the possible use of specific metabolites, detected by meta-omics analyses, as potential biomarkers for a CD non-invasive diagnosis. To highlight insights about metabolomics application in CD study, we conducted a narrative dissertation of selected original articles published in the last decade. By applying a systematic search, it clearly emerged how the metabolomic signature appears to be contradictory, as well as poorly investigated.}, }
@article {pmid35810835, year = {2022}, author = {Johnson, KV and Steenbergen, L}, title = {Do common antibiotic treatments influence emotional processing?.}, journal = {Physiology &amp; behavior}, volume = {255}, number = {}, pages = {113900}, doi = {10.1016/j.physbeh.2022.113900}, pmid = {35810835}, issn = {1873-507X}, mesh = {Adult ; Animals ; Anti-Bacterial Agents/pharmacology ; Anxiety/drug therapy ; Brain/physiology ; *Emotions ; *Gastrointestinal Microbiome/physiology ; Humans ; }, abstract = {Antibiotics are among the most commonly prescribed medications worldwide, yet research in recent years has revealed the detrimental effect they can have on the human microbiome, with implications for health. The community of microorganisms inhabiting the gut has been shown to regulate physiological and neural processes. Since studies in both humans and animal models have revealed that the gut microbiome can affect the brain, influencing emotion and cognition, here we investigate whether antibiotic treatment is associated with changes in emotional processing and mood with a between-subject design in 105 young healthy adult volunteers, using both psychological tests and questionnaires. As both the immune system and vagal signalling can mediate the microbiome-gut-brain axis, we also assess whether there is any evidence of such changes in participant physiology. We find that individuals who have taken antibiotics in the past three months show a stronger emotional bias towards sadness and at a physiological level they have a higher heart rate (though this does not mediate the relationship with negative bias). While we cannot rule out a possible role of prior infection, our findings are in any case highly relevant in light of research revealing that antibiotics are linked to increased susceptibility to depression and anxiety. Our results also have implications for listing antibiotic use as an exclusion criterion in studies on emotional processing and psychophysiology.}, }
@article {pmid35809795, year = {2022}, author = {Mukherjee, AG and Wanjari, UR and Bradu, P and Murali, R and Kannampuzha, S and Loganathan, T and C, GPD and Prakash B P, A and Renu, K and Dey, A and Vellingiri, B and Valsala Gopalakrishnan, A}, title = {The crosstalk of the human microbiome in breast and colon cancer: A metabolomics analysis.}, journal = {Critical reviews in oncology/hematology}, volume = {176}, number = {}, pages = {103757}, doi = {10.1016/j.critrevonc.2022.103757}, pmid = {35809795}, issn = {1879-0461}, mesh = {*Breast Neoplasms/therapy ; *Colonic Neoplasms/diagnosis/therapy ; Dysbiosis ; Female ; Humans ; Metabolomics/methods ; *Microbiota ; }, abstract = {The human microbiome's role in colon and breast cancer is described in this review. Understanding how the human microbiome and metabolomics interact with breast and colon cancer is the chief area of this study. First, the role of the gut and distal microbiome in breast and colon cancer is investigated, and the direct relationship between microbial dysbiosis and breast and colon cancer is highlighted. This work also focuses on the many metabolomic techniques used to locate prospective biomarkers, make an accurate diagnosis, and research new therapeutic targets for cancer treatment. This review clarifies the influence of anti-tumor medications on the microbiota and the proactive measures that can be taken to treat cancer using a variety of therapies, including radiotherapy, chemotherapy, next-generation biotherapeutics, gene-based therapy, integrated omics technology, and machine learning.}, }
@article {pmid35804891, year = {2022}, author = {McKeon, MG and Gallant, JN and Kim, YJ and Das, SR}, title = {It Takes Two to Tango: A Review of Oncogenic Virus and Host Microbiome Associated Inflammation in Head and Neck Cancer.}, journal = {Cancers}, volume = {14}, number = {13}, pages = {}, pmid = {35804891}, issn = {2072-6694}, abstract = {While the two primary risk factors for head and neck squamous cell carcinoma (HNSCC) are alcohol and tobacco, viruses account for an important and significant upward trend in HNSCC incidence. Human papillomavirus (HPV) is the causative agent for a subset of oropharyngeal squamous cell carcinoma (OPSCC)-a cancer that is impacting a rapidly growing group of typically middle-aged non-smoking white males. While HPV is a ubiquitously present (with about 1% of the population having high-risk oral HPV infection at any one time), less than 1% of those infected with high-risk strains develop OPSCC-suggesting that additional cofactors or coinfections may be required. Epstein-Barr virus (EBV) is a similarly ubiquitous virus that is strongly linked to nasopharyngeal carcinoma (NPC). Both of these viruses cause cellular transformation and chronic inflammation. While dysbiosis of the human microbiome has been associated with similar chronic inflammation and the pathogenesis of mucosal diseases (including OPSCC and NPC), a significant knowledge gap remains in understanding the role of bacterial-viral interactions in the initiation, development, and progression of head and neck cancers. In this review, we utilize the known associations of HPV with OPSCC and EBV with NPC to investigate these interactions. We thoroughly review the literature and highlight how perturbations of the pharyngeal microbiome may impact host-microbiome-tumor-viral interactions-leading to tumor growth.}, }
@article {pmid35803930, year = {2022}, author = {Schneider, KM and Mohs, A and Gui, W and Galvez, EJC and Candels, LS and Hoenicke, L and Muthukumarasamy, U and Holland, CH and Elfers, C and Kilic, K and Schneider, CV and Schierwagen, R and Strnad, P and Wirtz, TH and Marschall, HU and Latz, E and Lelouvier, B and Saez-Rodriguez, J and de Vos, W and Strowig, T and Trebicka, J and Trautwein, C}, title = {Imbalanced gut microbiota fuels hepatocellular carcinoma development by shaping the hepatic inflammatory microenvironment.}, journal = {Nature communications}, volume = {13}, number = {1}, pages = {3964}, pmid = {35803930}, issn = {2041-1723}, mesh = {Animals ; *Carcinoma, Hepatocellular/metabolism ; Dysbiosis/complications ; *Gastrointestinal Microbiome ; *Liver Neoplasms/metabolism ; Mice ; *Microbiota ; Tumor Microenvironment ; }, abstract = {Hepatocellular carcinoma (HCC) is a leading cause of cancer-related deaths worldwide, and therapeutic options for advanced HCC are limited. Here, we observe that intestinal dysbiosis affects antitumor immune surveillance and drives liver disease progression towards cancer. Dysbiotic microbiota, as seen in Nlrp6[-/-] mice, induces a Toll-like receptor 4 dependent expansion of hepatic monocytic myeloid-derived suppressor cells (mMDSC) and suppression of T-cell abundance. This phenotype is transmissible via fecal microbiota transfer and reversible upon antibiotic treatment, pointing to the high plasticity of the tumor microenvironment. While loss of Akkermansia muciniphila correlates with mMDSC abundance, its reintroduction restores intestinal barrier function and strongly reduces liver inflammation and fibrosis. Cirrhosis patients display increased bacterial abundance in hepatic tissue, which induces pronounced transcriptional changes, including activation of fibro-inflammatory pathways as well as circuits mediating cancer immunosuppression. This study demonstrates that gut microbiota closely shapes the hepatic inflammatory microenvironment opening approaches for cancer prevention and therapy.}, }
@article {pmid35798805, year = {2022}, author = {Blum, FC and Whitmire, JM and Bennett, JW and Carey, PM and Ellis, MW and English, CE and Law, NN and Tribble, DR and Millar, EV and Merrell, DS}, title = {Nasal microbiota evolution within the congregate setting imposed by military training.}, journal = {Scientific reports}, volume = {12}, number = {1}, pages = {11492}, pmid = {35798805}, issn = {2045-2322}, support = {Y1-Al-5072/AI/NIAID NIH HHS/United States ; }, mesh = {Cross-Sectional Studies ; Disease Susceptibility ; Georgia ; Humans ; Longitudinal Studies ; *Microbiota/genetics ; *Military Personnel/education ; *Nasal Cavity/microbiology ; RNA, Ribosomal, 16S/genetics ; Risk Factors ; Soft Tissue Infections/microbiology ; Staphylococcal Skin Infections/microbiology ; Staphylococcus aureus/genetics/isolation &amp; purification ; }, abstract = {The human microbiome is comprised of a complex and diverse community of organisms that is subject to dynamic changes over time. As such, cross-sectional studies of the microbiome provide a multitude of information for a specific body site at a particular time, but they fail to account for temporal changes in microbial constituents resulting from various factors. To address this shortcoming, longitudinal research studies of the human microbiome investigate the influence of various factors on the microbiome of individuals within a group or community setting. These studies are vital to address the effects of host and/or environmental factors on microbiome composition as well as the potential contribution of microbiome members during the course of an infection. The relationship between microbial constituents and disease development has been previously explored for skin and soft tissue infections (SSTIs) within congregate military trainees. Accordingly, approximately 25% of the population carries Staphylococcus aureus within their nasal cavity, and these colonized individuals are known to be at increased risk for SSTIs. To examine the evolution of the nasal microbiota of U.S. Army Infantry trainees, individuals were sampled longitudinally from their arrival at Fort Benning, Georgia, until completion of their training 90 days later. These samples were then processed to determine S. aureus colonization status and to profile the nasal microbiota using 16S rRNA gene-based methods. Microbiota stability differed dramatically among the individual trainees; some subjects exhibited great stability, some subjects showed gradual temporal changes and some subjects displayed a dramatic shift in nasal microbiota composition. Further analysis utilizing the available trainee metadata suggests that the major drivers of nasal microbiota stability may be S. aureus colonization status and geographic origin of the trainees. Nasal microbiota evolution within the congregate setting imposed by military training is a complex process that appears to be affected by numerous factors. This finding may indicate that future campaigns to prevent S. aureus colonization and future SSTIs among high-risk military trainees may require a 'personalized' approach.}, }
@article {pmid35794566, year = {2022}, author = {Sadrekarimi, H and Gardanova, ZR and Bakhshesh, M and Ebrahimzadeh, F and Yaseri, AF and Thangavelu, L and Hasanpoor, Z and Zadeh, FA and Kahrizi, MS}, title = {Emerging role of human microbiome in cancer development and response to therapy: special focus on intestinal microflora.}, journal = {Journal of translational medicine}, volume = {20}, number = {1}, pages = {301}, pmid = {35794566}, issn = {1479-5876}, mesh = {Bacteria ; Cell Transformation, Neoplastic ; Dysbiosis ; *Gastrointestinal Microbiome ; Gastrointestinal Tract/microbiology ; Humans ; *Microbiota ; }, abstract = {In recent years, there has been a greater emphasis on the impact of microbial populations inhabiting the gastrointestinal tract on human health and disease. According to the involvement of microbiota in modulating physiological processes (such as immune system development, vitamins synthesis, pathogen displacement, and nutrient uptake), any alteration in its composition and diversity (i.e., dysbiosis) has been linked to a variety of pathologies, including cancer. In this bidirectional relationship, colonization with various bacterial species is correlated with a reduced or elevated risk of certain cancers. Notably, the gut microflora could potentially play a direct or indirect role in tumor initiation and progression by inducing chronic inflammation and producing toxins and metabolites. Therefore, identifying the bacterial species involved and their mechanism of action could be beneficial in preventing the onset of tumors or controlling their advancement. Likewise, the microbial community affects anti-cancer approaches' therapeutic potential and adverse effects (such as immunotherapy and chemotherapy). Hence, their efficiency should be evaluated in the context of the microbiome, underlining the importance of personalized medicine. In this review, we summarized the evidence revealing the microbiota's involvement in cancer and its mechanism. We also delineated how microbiota could predict colon carcinoma development or response to current treatments to improve clinical outcomes.}, }
@article {pmid35794200, year = {2022}, author = {Singh, S and Natalini, JG and Segal, LN}, title = {Lung microbial-host interface through the lens of multi-omics.}, journal = {Mucosal immunology}, volume = {15}, number = {5}, pages = {837-845}, pmid = {35794200}, issn = {1935-3456}, support = {R37 CA244775/CA/NCI NIH HHS/United States ; }, mesh = {Computational Biology ; Humans ; Lung ; *Microbiota ; }, abstract = {In recent years, our understanding of the microbial world within us has been revolutionized by the use of culture-independent techniques. The use of multi-omic approaches can now not only comprehensively characterize the microbial environment but also evaluate its functional aspects and its relationship with the host immune response. Advances in bioinformatics have enabled high throughput and in-depth analyses of transcripts, proteins and metabolites and enormously expanded our understanding of the role of the human microbiome in different conditions. Such investigations of the lower airways have specific challenges but as the field develops, new approaches will be facilitated. In this review, we focus on how integrative multi-omics can advance our understanding of the microbial environment and its effects on the host immune tone in the lungs.}, }
@article {pmid35784474, year = {2022}, author = {Mi, J and Wang, S and Liu, P and Liu, C and Zhuang, D and Leng, X and Zhang, Q and Bai, F and Feng, Q and Wu, X}, title = {CUL4B Upregulates RUNX2 to Promote the Osteogenic Differentiation of Human Periodontal Ligament Stem Cells by Epigenetically Repressing the Expression of miR-320c and miR-372/373-3p.}, journal = {Frontiers in cell and developmental biology}, volume = {10}, number = {}, pages = {921663}, pmid = {35784474}, issn = {2296-634X}, abstract = {Mesenchymal stem cells (MSCs) within the periodontal ligament (PDL), termed periodontal ligament stem cells (PDLSCs), have a self-renewing capability and a multidirectional differentiation potential. The molecular mechanisms that regulate multidirectional differentiation, such as the osteogenic differentiation of PDLSCs, remain to be elucidated. Cullin 4B (CUL4B), which assembles the CUL4B-RING ubiquitin ligase (CRL4B) complex, is involved in regulating a variety of developmental and physiological processes including the skeletal development and stemness of cancer stem cells. However, nothing is known about the possible role of CUL4B in the osteogenic differentiation of PDLSCs. Here, we found that knockdown of CUL4B decreased the proliferation, migration, stemness and osteogenic differentiation ability of PDLSCs. Mechanistically, we demonstrate that CUL4B cooperates with the PRC2 complex to repress the expression of miR-320c and miR-372/373-3p, which results in the upregulation of RUNX2, a master transcription factor (TF) that regulates osteogenic differentiation. In brief, the present study reveals the role of CUL4B as a new regulator of osteogenic differentiation in PDLSCs.}, }
@article {pmid35783436, year = {2022}, author = {Wang, L and Li, F and Gu, B and Qu, P and Liu, Q and Wang, J and Tang, J and Cai, S and Zhao, Q and Ming, Z}, title = {Metaomics in Clinical Laboratory: Potential Driving Force for Innovative Disease Diagnosis.}, journal = {Frontiers in microbiology}, volume = {13}, number = {}, pages = {883734}, pmid = {35783436}, issn = {1664-302X}, abstract = {Currently, more and more studies suggested that reductionism was lack of holistic and integrative view of biological processes, leading to limited understanding of complex systems like microbiota and the associated diseases. In fact, microbes are rarely present in individuals but normally live in complex multispecies communities. With the recent development of a variety of metaomics techniques, microbes could be dissected dynamically in both temporal and spatial scales. Therefore, in-depth understanding of human microbiome from different aspects such as genomes, transcriptomes, proteomes, and metabolomes could provide novel insights into their functional roles, which also holds the potential in making them diagnostic biomarkers in many human diseases, though there is still a huge gap to fill for the purpose. In this mini-review, we went through the frontlines of the metaomics techniques and explored their potential applications in clinical diagnoses of human diseases, e.g., infectious diseases, through which we concluded that novel diagnostic methods based on human microbiomes shall be achieved in the near future, while the limitations of these techniques such as standard procedures and computational challenges for rapid and accurate analysis of metaomics data in clinical settings were also examined.}, }
@article {pmid35777465, year = {2022}, author = {Yang, S and Wang, S and Wang, Y and Rong, R and Kim, J and Li, B and Koh, AY and Xiao, G and Li, Q and Liu, DJ and Zhan, X}, title = {MB-SupCon: Microbiome-based Predictive Models via Supervised Contrastive Learning.}, journal = {Journal of molecular biology}, volume = {434}, number = {15}, pages = {167693}, pmid = {35777465}, issn = {1089-8638}, support = {U01 AI169298/AI/NIAID NIH HHS/United States ; R01 GM126479/GM/NIGMS NIH HHS/United States ; R56 HG011035/HG/NHGRI NIH HHS/United States ; R01 CA231303/CA/NCI NIH HHS/United States ; R01 HG008983/HG/NHGRI NIH HHS/United States ; R01 CA245318/CA/NCI NIH HHS/United States ; U01 CA249245/CA/NCI NIH HHS/United States ; R35 GM136375/GM/NIGMS NIH HHS/United States ; R01 HG011035/HG/NHGRI NIH HHS/United States ; }, mesh = {Diabetes Mellitus, Type 2/genetics/microbiology ; Humans ; Inflammatory Bowel Diseases/genetics/microbiology ; *Metabolome ; Metabolomics/methods ; *Microbiota ; RNA, Ribosomal, 16S/genetics ; *Supervised Machine Learning ; }, abstract = {Human microbiome consists of trillions of microorganisms. Microbiota can modulate the host physiology through molecule and metabolite interactions. Integrating microbiome and metabolomics data have the potential to predict different diseases more accurately. Yet, most datasets only measure microbiome data but without paired metabolome data. Here, we propose a novel integrative modeling framework, Microbiome-based Supervised Contrastive Learning Framework (MB-SupCon). MB-SupCon integrates microbiome and metabolome data to generate microbiome embeddings, which can be used to improve the prediction accuracy in datasets that only measure microbiome data. As a proof of concept, we applied MB-SupCon on 720 samples with paired 16S microbiome data and metabolomics data from patients with type 2 diabetes. MB-SupCon outperformed existing prediction methods and achieved high average prediction accuracies for insulin resistance status (84.62%), sex (78.98%), and race (80.04%). Moreover, the microbiome embeddings form separable clusters for different covariate groups in the lower-dimensional space, which enhances data visualization. We also applied MB-SupCon on a large inflammatory bowel disease study and observed similar advantages. Thus, MB-SupCon could be broadly applicable to improve microbiome prediction models in multi-omics disease studies.}, }
@article {pmid35776498, year = {2023}, author = {Hong, SY and Xia, QD and Yang, YY and Li, C and Zhang, JQ and Xu, JZ and Qin, BL and Xun, Y and Wang, SG}, title = {The role of microbiome: a novel insight into urolithiasis.}, journal = {Critical reviews in microbiology}, volume = {49}, number = {2}, pages = {177-196}, doi = {10.1080/1040841X.2022.2045899}, pmid = {35776498}, issn = {1549-7828}, mesh = {Humans ; *Urolithiasis/complications ; *Urinary Calculi/etiology ; Kidney ; *Microbiota ; *Gastrointestinal Microbiome ; }, abstract = {Urolithiasis, referred to as the formation of stones in the urinary tract, is a common disease with growing prevalence and high recurrence rate worldwide. Although researchers have endeavoured to explore the mechanism of urinary stone formation for novel effective therapeutic and preventative measures, the exact aetiology and pathogenesis remain unclear. Propelled by sequencing technologies and culturomics, great advances have been made in understanding the pivotal contribution of the human microbiome to urolithiasis. Indeed, there are diverse and abundant microbes interacting with the host in the urinary tract, overturning the dogma that urinary system, and urine are sterile. The urinary microbiome of stone formers was clearly distinct from healthy individuals. Besides, dysbiosis of the intestinal microbiome appears to be involved in stone formation through the gut-kidney axis. Thus, the human microbiome has potential significant implications for the aetiology of urolithiasis, providing a novel insight into diagnostic, therapeutic, and prognostic strategies. Herein, we review and summarize the landmark microbiome studies in urolithiasis and identify therapeutic implications, challenges, and future perspectives in this rapidly evolving field. To conclude, a new front has opened with the evidence for a microbial role in stone formation, offering potential applications in the prevention, and treatment of urolithiasis.}, }
@article {pmid35769561, year = {2022}, author = {Ndika, J and Karisola, P and Lahti, V and Fyhrquist, N and Laatikainen, T and Haahtela, T and Alenius, H}, title = {Epigenetic Differences in Long Non-coding RNA Expression in Finnish and Russian Karelia Teenagers With Contrasting Risk of Allergy and Asthma.}, journal = {Frontiers in allergy}, volume = {3}, number = {}, pages = {878862}, pmid = {35769561}, issn = {2673-6101}, abstract = {BACKGROUND: Previously, we investigated skin microbiota and blood cell gene expression in Finnish and Russian teenagers with contrasting incidence of allergic conditions. The microbiota and transcriptomic signatures were distinctly different, with high Acinetobacter abundance and suppression of genes regulating innate immune response in healthy subjects.<br><br>OBJECTIVE: Here, we investigated long non-coding RNA (lncRNA) expression profiles of blood mononuclear cells (PBMC) from healthy and allergic subjects, to identify lncRNAs that act at the interphase of microbiome-mediated immune homeostasis in allergy/asthma.<br><br>METHODS: Genome-wide co-expression network analyses of blood cell lncRNA/mRNA expression was integrated with skin microbiota profiles of Finnish (69) and Russian (75) subjects. Selected lncRNAs were validated by stimulation of cohort-derived PBMCs and a macrophage cell model with birch pollen allergen (Betv1) or lipopolysaccharide, respectively.<br><br>RESULTS: Finnish and Russian PBMCs were differentiated by 3,818 lncRNA transcripts. In the Finnish subjects with high prevalence of allergy and asthma, a subset of 37 downregulated lncRNAs (including, FAM155A-IT1 and LOC400958) were identified. They were part of a co-expression network with 20 genes known to be related to asthma and allergic rhinitis (R > 0.95). Incidentally, all these 20 genes were also components of pathways corresponding to cellular response to bacterium. The Finnish and Russian samples were also differentiated by the abundance of 176 bacterial OTU (operational taxonomic units). The subset of 37 lncRNAs, associated with allergy, was most correlated with the abundance of Acinetobacter (R > +0.5), Jeotgalicoccus (R > +0.5), Corynebacterium (R < -0.5) and Micrococcus (R < -0.5).<br><br>CONCLUSION: In Finnish and Russian teenagers with contrasting allergy and asthma prevalence, epigenetic differences in lncRNA expression appear to be important components of the underlying microbiota-immune interactions. Unraveling the functions of the 37 differing lncRNAs may be the key to understanding microbiome-immune crosstalk, and to develop clinically relevant biomarkers.}, }
@article {pmid35768415, year = {2022}, author = {Kainulainen, V and von Schantz-Fant, C and Kovanen, RM and Potdar, S and Laamanen, K and Saarela, J and Satokari, R}, title = {Genome-wide siRNA screening reveals several host receptors for the binding of human gut commensal Bifidobacterium bifidum.}, journal = {NPJ biofilms and microbiomes}, volume = {8}, number = {1}, pages = {50}, pmid = {35768415}, issn = {2055-5008}, mesh = {Bifidobacterium/genetics/metabolism ; *Bifidobacterium bifidum/genetics ; Caco-2 Cells ; HT29 Cells ; Humans ; Infant ; RNA, Small Interfering/genetics/metabolism ; }, abstract = {Bifidobacterium spp. are abundant gut commensals, especially in breast-fed infants. Bifidobacteria are associated with many health-promoting effects including maintenance of epithelial barrier and integrity as well as immunomodulation. However, the protective mechanisms of bifidobacteria on intestinal epithelium at molecular level are poorly understood. In this study, we developed a high-throughput in vitro screening assay to explore binding receptors of intestinal epithelial cells for Bifidobacterium bifidum. Short interfering RNAs (siRNA) were used to silence expression of each gene in the Caco-2 cell line one by one. The screen yielded four cell surface proteins, SERPINB3, LGICZ1, PKD1 and PAQR6, which were identified as potential receptors as the siRNA knock-down of their expression decreased adhesion of B. bifidum to the cell line repeatedly during the three rounds of siRNA screening. Furthermore, blocking of these host cell proteins by specific antibodies decreased the binding of B. bifidum significantly to Caco-2 and HT29 cell lines. All these molecules are located on the surface of epithelial cells and three out of four, SERPINB3, PKD1 and PAQR6, are involved in the regulation of cellular processes related to proliferation, differentiation and apoptosis as well as inflammation and immunity. Our results provide leads to the first steps in the mechanistic cascade of B. bifidum-host interactions leading to regulatory effects in the epithelium and may partly explain how this commensal bacterium is able to promote intestinal homeostasis.}, }
@article {pmid35761544, year = {2022}, author = {Farias da Cruz, M and Baraúna Magno, M and Alves Jural, L and Pimentel, TC and Masterson Tavares Pereira Ferreira, D and Almeida Esmerino, E and Luis Paiva Anciens Ramos, G and Vicente Gomila, J and Cristina Silva, M and Cruz, AGD and da Silva Fidalgo, TK and Cople Maia, L}, title = {Probiotics and dairy products in dentistry: A bibliometric and critical review of randomized clinical trials.}, journal = {Food research international (Ottawa, Ont.)}, volume = {157}, number = {}, pages = {111228}, doi = {10.1016/j.foodres.2022.111228}, pmid = {35761544}, issn = {1873-7145}, mesh = {Adolescent ; Adult ; Aged ; Animals ; Bibliometrics ; *COVID-19 ; Child ; *Dental Caries/prevention &amp; control ; Dentistry ; Humans ; Milk/microbiology ; *Periodontal Diseases ; *Probiotics/therapeutic use ; Randomized Controlled Trials as Topic ; }, abstract = {The oral environment is an essential part of the human microbiome. The consumption of probiotic products may improve the oral microbiota and reduce the risk of diseases. This paper presents a bibliometric and critical review of randomized clinical trials (RCTs) that used probiotics to analyze oral parameters in humans. RCTs carried out with no age, gender, and ethnicity restrictions and published in the pre-COVID-19 period were included. Furthermore, the utilization of probiotic dairy products to improve oral health is discussed. The bibliometric review demonstrated that 'Microbiology,' 'Dental caries,' and 'Streptococcus mutants' were the most highlighted keywords. Furthermore, Sweden and India have the highest number of publications. The most prevalent outcomes were 'salivary parameters,' 'periodontal disease,' and 'dental caries.' The most used vehicles for probiotic administration were pharmaceutical formulas and dairy products. The administration of probiotic dairy products could modify the oral microbiota (reductions in S. mutans counts), influence the caries development and periodontal disease in children, adolescents, adults, and the elderly, and improve gingival health. The main probiotic dairy products investigated were milk, fermented milk, yogurt, kefir, curd, and cheese. Lacticaseibacillus paracasei SD1 was the most used probiotic culture. The studies demonstrated that the probiotic effect lasted 2-4 weeks after discontinuing consumption. However, the results depended on the subject type, study design, probiotic strain and concentration, and dairy product type. In conclusion, probiotic dairy products are promising alternatives to improve oral health.}, }
@article {pmid35759916, year = {2022}, author = {Kervinen, K and Holster, T and Saqib, S and Virtanen, S and Stefanovic, V and Rahkonen, L and Nieminen, P and Salonen, A and Kalliala, I}, title = {Parity and gestational age are associated with vaginal microbiota composition in term and late term pregnancies.}, journal = {EBioMedicine}, volume = {81}, number = {}, pages = {104107}, pmid = {35759916}, issn = {2352-3964}, mesh = {Cesarean Section ; Cross-Sectional Studies ; Female ; Gestational Age ; Humans ; Infant, Newborn ; *Microbiota/genetics ; Parity ; Pregnancy ; *Premature Birth ; RNA, Ribosomal, 16S/genetics ; Vagina ; }, abstract = {BACKGROUND: Vaginal microbiota and its potential contribution to preterm birth is under intense research. However, only few studies have investigated the vaginal microbiota in later stages of pregnancy or at the onset of labour.<br><br>METHODS: We used 16S rRNA gene amplicon sequencing to analyse cross-sectional vaginal swab samples from 324 Finnish women between 37-42 weeks of gestation, sampled before elective caesarean section, at the onset of spontaneous labour, and in pregnancies lasting &#x2265;41 weeks of gestation. Microbiota data were combined with comprehensive clinical data to identify factors associated with microbiota variation.<br><br>FINDINGS: Vaginal microbiota composition associated strongly with advancing gestational age and parity, i.e. presence of previous deliveries. Absence of previous deliveries was a strong predictor of Lactobacillus crispatus dominated vaginal microbiota, and the relative abundance of L. crispatus was higher in late term pregnancies, especially among nulliparous women.<br><br>INTERPRETATION: This study identified late term pregnancy and reproductive history as factors underlying high abundance of gynaecological health-associated L. crispatus in pregnant women. Our results suggest that the vaginal microbiota affects or reflects the regulation of the duration of gestation and labour onset, with potentially vast clinical utilities. Further studies are needed to address the causality and the mechanisms on how previous labour, but not pregnancy, affects the vaginal microbiota. Parity and gestational age should be accounted for in future studies on vaginal microbiota and reproductive outcomes.<br><br>FUNDING: This research was supported by EU H2020 programme Sweet Crosstalk ITN (814102), Academy of Finland, State Research Funding, and University of Helsinki.}, }
@article {pmid35756062, year = {2022}, author = {Vernocchi, P and Ristori, MV and Guerrera, S and Guarrasi, V and Conte, F and Russo, A and Lupi, E and Albitar-Nehme, S and Gardini, S and Paci, P and Ianiro, G and Vicari, S and Gasbarrini, A and Putignani, L}, title = {Gut Microbiota Ecology and Inferred Functions in Children With ASD Compared to Neurotypical Subjects.}, journal = {Frontiers in microbiology}, volume = {13}, number = {}, pages = {871086}, pmid = {35756062}, issn = {1664-302X}, abstract = {Autism spectrum disorders (ASDs) is a multifactorial neurodevelopmental disorder. The communication between the gastrointestinal (GI) tract and the central nervous system seems driven by gut microbiota (GM). Herein, we provide GM profiling, considering GI functional symptoms, neurological impairment, and dietary habits. Forty-one and 35 fecal samples collected from ASD and neurotypical children (CTRLs), respectively, (age range, 3-15 years) were analyzed by 16S targeted-metagenomics (the V3-V4 region) and inflammation and permeability markers (i.e., sIgA, zonulin lysozyme), and then correlated with subjects' metadata. Our ASD cohort was characterized as follows: 30/41 (73%) with GI functional symptoms; 24/41 (58%) picky eaters (PEs), with one or more dietary needs, including 10/41 (24%) with food selectivity (FS); 36/41 (88%) presenting high and medium autism severity symptoms (HMASSs). Among the cohort with GI symptoms, 28/30 (93%) showed HMASSs, 17/30 (57%) were picky eaters and only 8/30 (27%) with food selectivity. The remaining 11/41 (27%) ASDs without GI symptoms that were characterized by HMASS for 8/11 (72%) and 7/11 (63%) were picky eaters. GM ecology was investigated for the overall ASD cohort versus CTRLs; ASDs with GI and without GI, respectively, versus CTRLs; ASD with GI versus ASD without GI; ASDs with HMASS versus low ASSs; PEs versus no-PEs; and FS versus absence of FS. In particular, the GM of ASDs, compared to CTRLs, was characterized by the increase of Proteobacteria, Bacteroidetes, Rikenellaceae, Pasteurellaceae, Klebsiella, Bacteroides, Roseburia, Lactobacillus, Prevotella, Sutterella, Staphylococcus, and Haemophilus. Moreover, Sutterella, Roseburia and Fusobacterium were associated to ASD with GI symptoms compared to CTRLs. Interestingly, ASD with GI symptoms showed higher value of zonulin and lower levels of lysozyme, which were also characterized by differentially expressed predicted functional pathways. Multiple machine learning models classified correctly 80% overall ASDs, compared with CTRLs, based on Bacteroides, Lactobacillus, Prevotella, Staphylococcus, Sutterella, and Haemophilus features. In conclusion, in our patient cohort, regardless of the evaluation of many factors potentially modulating the GM profile, the major phenotypic determinant affecting the GM was represented by GI hallmarks and patients' age.}, }
@article {pmid35750322, year = {2022}, author = {Kelly, MS and Bunyavanich, S and Phipatanakul, W and Lai, PS}, title = {The Environmental Microbiome, Allergic Disease, and Asthma.}, journal = {The journal of allergy and clinical immunology. In practice}, volume = {10}, number = {9}, pages = {2206-2217.e1}, pmid = {35750322}, issn = {2213-2201}, support = {R01 AI147028/AI/NIAID NIH HHS/United States ; U01 AI110397/AI/NIAID NIH HHS/United States ; U19 AI136053/AI/NIAID NIH HHS/United States ; U01 AI160082/AI/NIAID NIH HHS/United States ; K23 ES023700/ES/NIEHS NIH HHS/United States ; R01 AI144119/AI/NIAID NIH HHS/United States ; K24 AI106822/AI/NIAID NIH HHS/United States ; R01 AI118833/AI/NIAID NIH HHS/United States ; R38 HL150212/HL/NHLBI NIH HHS/United States ; }, mesh = {*Asthma/complications ; Environmental Exposure/adverse effects ; Humans ; *Hypersensitivity/epidemiology/etiology ; *Microbiota ; }, abstract = {The environmental microbiome represents the entirety of the microbes and their metabolites that we encounter in our environments. A growing body of evidence supports the role of the environmental microbiome in risk for and severity of allergic diseases and asthma. The environmental microbiome represents a ubiquitous, lifelong exposure to non-self antigens. During the critical window between birth and 1 year of life, interactions between our early immune system and the environmental microbiome have 2 consequences: our individual microbiome is populated by environmental microbes, and our immune system is trained regarding which antigens to tolerate. During this time, a diversity of exposures appears largely protective, dramatically decreasing the risk of developing allergic diseases and asthma. As we grow older, our interactions with the environmental microbiome change. While it continues to exert influence over the composition of the human microbiome, the environmental microbiome becomes increasingly a source for antigenic stimulation and infection. The same microbial exposure protective against disease development may exacerbate disease severity. Although much has been learned about the importance of the environmental microbiome in allergic disease, much more remains to be understood about these complicated interactions between our environment, our microbiome, our immune system, and disease.}, }
@article {pmid35748030, year = {2022}, author = {Pang, Z and Launonen, H and Korpela, R and Vapaatalo, H}, title = {Local aldosterone synthesis in the large intestine of mouse: An ex vivo incubation study.}, journal = {The Journal of international medical research}, volume = {50}, number = {6}, pages = {3000605221105163}, pmid = {35748030}, issn = {1473-2300}, mesh = {*Aldosterone ; Angiotensin II/pharmacology ; Animals ; Corticosterone ; *Cytochrome P-450 CYP11B2 ; Humans ; Intestine, Large/metabolism ; Male ; Mice ; Mice, Inbred DBA ; Sodium ; }, abstract = {OBJECTIVE: To investigate the regulation of local aldosterone synthesis by physiological stimulants in the murine gut.<br><br>METHODS: Male mice were fed for 14 days with normal, high (1.6%) or low (0.01%) sodium diets. Tissue liver receptor homolog-1 and aldosterone in the colon and caecum were detected using an enzyme-linked immunosorbent assay (ELISA). Released corticosterone and aldosterone in tissue incubation experiments after stimulation with angiotensin II (Ang II) and dibutyryl-cAMP (DBA; the second messenger of adrenocorticotropic hormone) were assayed using an ELISA. Tissue aldosterone synthase (CYP11B2) protein levels were measured using an ELISA and Western blots.<br><br>RESULTS: In incubated colon tissues, aldosterone synthase levels were increased by a low-sodium diet; and by Ang II and DBA in the normal diet group. Release of aldosterone into the incubation buffer was increased from the colon by a low-sodium diet and decreased by a high-sodium diet in parallel with changes in aldosterone synthase levels. In mice fed a normal diet, colon incubation with both Ang II and DBA increased the release of aldosterone as well as its precursor corticosterone.<br><br>CONCLUSION: Local aldosterone synthesis in the large intestine is stimulated by a low-sodium diet, dibutyryl-cAMP and Ang II similar to the adrenal glands.}, }
@article {pmid35744617, year = {2022}, author = {García-Mato, E and Martínez-Lamas, L and Álvarez-Fernández, M and Varela-Aneiros, I and Diniz-Freitas, M and Limeres-Posse, J and Diz-Dios, P}, title = {Molecular Detection of Streptococcus downii sp. nov. from Dental Plaque Samples from Patients with Down Syndrome and Non-Syndromic Individuals.}, journal = {Microorganisms}, volume = {10}, number = {6}, pages = {}, pmid = {35744617}, issn = {2076-2607}, abstract = {A new bacterial species has recently been identified in the dental plaque of an adolescent with Down syndrome. The species is known as Streptococcus downii sp. nov. (abbreviated to S. downii), and it inhibits the growth of S. mutans and certain periodontal pathogens. The aim of this study was to determine the distribution of S. downii in the oral cavity of individuals with Down syndrome. Methods: A specific polymerase chain reaction for the operon of bacteriocin (class IIb lactobin A/cerein 7B family) was designed to detect S. downii in individuals with Down syndrome (n = 200) and in the general population (n = 100). We also compared the whole genome of S. downii and the regions related to its bacteriocins against 127 metagenomes of supragingival plaque of the "Human Microbiome Project". Results: We detected the specific gene of the S. downii bacteriocin in an individual with Down syndrome (Cq, 34.52; GE/μL, 13.0) and in an individual of the non-syndromic control group (Cq, 34.78 Cq; GE/μL, 4.93). The prevalence of S. downii was ≤1% both in Down syndrome and in the general population, which did not allow for clinical-microbiological correlations to be established. This result was confirmed by detecting only one metagenome with an ANIm with approximately 95% homology and with 100% homology with ORFs that code class IIb lactobiocin A/cerein 7B bacteriocins among the 127 metagenomes of the "Human Microbiome Project" tested. Conclusions: The detection rate of S. downii in the supragingival dental plaque was very low, both in the Down syndrome individuals and in the non-syndromic controls. A clinical-microbiological correlation could therefore not be established.}, }
@article {pmid35743789, year = {2022}, author = {Graziani, C and Laterza, L and Talocco, C and Pizzoferrato, M and Di Simone, N and D'Ippolito, S and Ricci, C and Gervasoni, J and Persichilli, S and Del Chierico, F and Marzano, V and Mortera, SL and Primiano, A and Poscia, A and Ponziani, FR and Putignani, L and Urbani, A and Petito, V and Di Vincenzo, F and Masi, L and Lopetuso, LR and Cammarota, G and Romualdi, D and Lanzone, A and Gasbarrini, A and Scaldaferri, F}, title = {Intestinal Permeability and Dysbiosis in Female Patients with Recurrent Cystitis: A Pilot Study.}, journal = {Journal of personalized medicine}, volume = {12}, number = {6}, pages = {}, pmid = {35743789}, issn = {2075-4426}, abstract = {Recurrent cystitis (RC) is a common disease, especially in females. Anatomical, behavioral and genetic predisposing factors are associated with the ascending retrograde route, which often causes bladder infections. RC seems to be mainly caused by agents derived from the intestinal microbiota, and most frequently by Escherichia coli. Intestinal contiguity contributes to the etiopathogenesis of RC and an alteration in intestinal permeability could have a major role in RC. The aim of this pilot study is to assess gut microbiome dysbiosis and intestinal permeability in female patients with RC. Patients with RC (n = 16) were enrolled and compared with healthy female subjects (n = 15) and patients with chronic gastrointestinal (GI) disorders (n = 238). We calculated the Acute Cystitis Symptom Score/Urinary Tract Infection Symptom Assessment (ACSS/UTISA) and Gastrointestinal Symptom Rating Scale (GSRS) scores and evaluated intestinal permeability and the fecal microbiome in the first two cohorts. Patients with RC showed an increased prevalence of gastrointestinal symptoms compared with healthy controls. Of the patients with RC, 88% showed an increased intestinal permeability with reduced biodiversity of gut microbiota compared to healthy controls, and 68% of the RC patients had a final diagnosis of gastrointestinal disease. Similarly, GI patients reported a higher incidence of urinary symptoms with a diagnosis of RC in 20%. Gut barrier impairment seems to play a major role in the pathogenesis of RC. Further studies are necessary to elucidate the role of microbiota and intestinal permeability in urinary tract infections.}, }
@article {pmid35743209, year = {2022}, author = {Guan, Z and Feng, Q}, title = {Chitosan and Chitooligosaccharide: The Promising Non-Plant-Derived Prebiotics with Multiple Biological Activities.}, journal = {International journal of molecular sciences}, volume = {23}, number = {12}, pages = {}, pmid = {35743209}, issn = {1422-0067}, support = {82071122//National Natural Science Foundation of China/ ; }, mesh = {Animals ; Chitin ; *Chitosan/chemistry ; Humans ; Oligosaccharides/chemistry/pharmacology ; Prebiotics ; Prospective Studies ; }, abstract = {Biodegradable chitin is the second-most abundant natural polysaccharide, widely existing in the exoskeletons of crabs, shrimps, insects, and the cell walls of fungi. Chitosan and chitooligosaccharide (COS, also named chitosan oligosaccharide) are the two most important deacetylated derivatives of chitin. Compared with chitin, chitosan and COS not only have more satisfactory physicochemical properties but also exhibit additional biological activities, which cause them to be widely applied in the fields of food, medicine, and agriculture. Additionally, due to their significant ability to improve gut microbiota, chitosan and COS are deemed prospective prebiotics. Here, we introduced the production, physicochemical properties, applications, and pharmacokinetic characteristics of chitosan and COS. Furthermore, we summarized the latest research on their antioxidant, anti-inflammatory, and antimicrobial activities. Research progress on the prebiotic functions of chitosan and COS is particularly reviewed. We creatively analyzed and discussed the mechanisms and correlations underlying these activities of chitosan and COS and their physicochemical properties. Our work enriched people's understanding of these non-plant-derived prebiotics. Based on this review, the future directions of research on chitosan and COS are explored. Collectively, optimizing the production technology of chitin derivatives and enriching understanding of their biological functions will shed more light on their capability to improve human health.}, }
@article {pmid35741811, year = {2022}, author = {Wu, Q and O'Malley, J and Datta, S and Gharaibeh, RZ and Jobin, C and Karagas, MR and Coker, MO and Hoen, AG and Christensen, BC and Madan, JC and Li, Z}, title = {MarZIC: A Marginal Mediation Model for Zero-Inflated Compositional Mediators with Applications to Microbiome Data.}, journal = {Genes}, volume = {13}, number = {6}, pages = {}, pmid = {35741811}, issn = {2073-4425}, support = {UH3 OD023275/OD/NIH HHS/United States ; R01 GM123014/GM/NIGMS NIH HHS/United States ; R01 LM012723/LM/NLM NIH HHS/United States ; P30 CA023108/CA/NCI NIH HHS/United States ; P01 ES022832/ES/NIEHS NIH HHS/United States ; P20 GM104416/GM/NIGMS NIH HHS/United States ; }, mesh = {Computer Simulation ; Humans ; *Microbiota/genetics ; *Models, Statistical ; Research Design ; }, abstract = {BACKGROUND: The human microbiome can contribute to pathogeneses of many complex diseases by mediating disease-leading causal pathways. However, standard mediation analysis methods are not adequate to analyze the microbiome as a mediator due to the excessive number of zero-valued sequencing reads in the data and that the relative abundances have to sum to one. The two main challenges raised by the zero-inflated data structure are: (a) disentangling the mediation effect induced by the point mass at zero; and (b) identifying the observed zero-valued data points that are not zero (i.e., false zeros).<br><br>METHODS: We develop a novel marginal mediation analysis method under the potential-outcomes framework to address the issues. We also show that the marginal model can account for the compositional structure of microbiome data.<br><br>RESULTS: The mediation effect can be decomposed into two components that are inherent to the two-part nature of zero-inflated distributions. With probabilistic models to account for observing zeros, we also address the challenge with false zeros. A comprehensive simulation study and the application in a real microbiome study showcase our approach in comparison with existing approaches.<br><br>CONCLUSIONS: When analyzing the zero-inflated microbiome composition as the mediators, MarZIC approach has better performance than standard causal mediation analysis approaches and existing competing approach.}, }
@article {pmid35740129, year = {2022}, author = {Grada, A and Ghannoum, MA and Bunick, CG}, title = {Sarecycline Demonstrates Clinical Effectiveness against Staphylococcal Infections and Inflammatory Dermatoses: Evidence for Improving Antibiotic Stewardship in Dermatology.}, journal = {Antibiotics (Basel, Switzerland)}, volume = {11}, number = {6}, pages = {}, pmid = {35740129}, issn = {2079-6382}, abstract = {Tetracycline class antibiotics are widely used for multiple skin diseases, including acne vulgaris, acne rosacea, cutaneous infections, inflammatory dermatoses, and autoimmune blistering disorders. Concerns about antibiotic resistance and protecting the human/host microbiome beg the question whether broad-spectrum tetracyclines such as doxycycline and minocycline should be prescribed at such a high rate by dermatologists when a narrow-spectrum tetracycline derivative, sarecycline, exists. We evaluated the clinical effectiveness of oral sarecycline against cutaneous staphylococcal infections, eyelid stye, and mucous membrane pemphigoid to determine whether sarecycline is a viable option for clinicians to practice improved antibiotic stewardship. We observed significant improvement in staphylococcal infections and inflammatory dermatoses with courses of oral sarecycline as short as 9 days, with no reported adverse events. These clinical findings are consistent with in vitro microbiological data and anti-inflammatory properties of sarecycline. Our data provides a strong rationale for clinicians to use narrow-spectrum sarecycline rather than broad-spectrum tetracyclines as a first-line agent in treating staphylococcal skin infections and inflammatory skin diseases for which tetracyclines are currently commonly employed. Such advancement in the practice paradigm in dermatology will enhance antibiotic stewardship, reduce risk of antibiotic resistance, protect the human microbiome, and provide patients with precision medicine care.}, }
@article {pmid35739354, year = {2022}, author = {Cani, PD and Depommier, C and Derrien, M and Everard, A and de Vos, WM}, title = {Author Correction: Akkermansia muciniphila: paradigm for next-generation beneficial microorganisms.}, journal = {Nature reviews. Gastroenterology &amp; hepatology}, volume = {19}, number = {10}, pages = {682}, doi = {10.1038/s41575-022-00650-6}, pmid = {35739354}, issn = {1759-5053}, }
@article {pmid35732630, year = {2022}, author = {Sharp, C and Foster, KR}, title = {Host control and the evolution of cooperation in host microbiomes.}, journal = {Nature communications}, volume = {13}, number = {1}, pages = {3567}, pmid = {35732630}, issn = {2041-1723}, support = {/WT_/Wellcome Trust/United Kingdom ; 209397/Z/17/Z/WT_/Wellcome Trust/United Kingdom ; }, mesh = {Animals ; Bacteria/genetics ; Biological Evolution ; *Microbiota/genetics ; Phylogeny ; *Symbiosis ; }, abstract = {Humans, and many other species, are host to diverse symbionts. It is often suggested that the mutual benefits of host-microbe relationships can alone explain cooperative evolution. Here, we evaluate this hypothesis with evolutionary modelling. Our model predicts that mutual benefits are insufficient to drive cooperation in systems like the human microbiome, because of competition between symbionts. However, cooperation can emerge if hosts can exert control over symbionts, so long as there are constraints that limit symbiont counter evolution. We test our model with genomic data of two bacterial traits monitored by animal immune systems. In both cases, bacteria have evolved as predicted under host control, tending to lose flagella and maintain butyrate production when host-associated. Moreover, an analysis of bacteria that retain flagella supports the evolution of host control, via toll-like receptor 5, which limits symbiont counter evolution. Our work puts host control mechanisms, including the immune system, at the centre of microbiome evolution.}, }
@article {pmid35729515, year = {2022}, author = {Dai, W and Li, C and Li, T and Hu, J and Zhang, H}, title = {Super-taxon in human microbiome are identified to be associated with colorectal cancer.}, journal = {BMC bioinformatics}, volume = {23}, number = {1}, pages = {243}, pmid = {35729515}, issn = {1471-2105}, support = {DMS-2112711//National Science Foundation, United States/ ; R01 HG010171/HG/NHGRI NIH HHS/United States ; R01 MH116527/MH/NIMH NIH HHS/United States ; UL1 TR001863/TR/NCATS NIH HHS/United States ; R01MH116527 and R01HG010171/NH/NIH HHS/United States ; }, mesh = {*Colorectal Neoplasms/genetics ; Firmicutes ; Humans ; *Microbiota/genetics ; Peptostreptococcus ; }, abstract = {BACKGROUND: Microbial communities in the human body, also known as human microbiota, impact human health, such as colorectal cancer (CRC). However, the different roles that microbial communities play in healthy and disease hosts remain largely unknown. The microbial communities are typically recorded through the taxa counts of operational taxonomic units (OTUs). The sparsity and high correlations among OTUs pose major challenges for understanding the microbiota-disease relation. Furthermore, the taxa data are structured in the sense that OTUs are related evolutionarily by a hierarchical structure.<br><br>RESULTS: In this study, we borrow the idea of super-variant from statistical genetics, and propose a new concept called super-taxon to exploit hierarchical structure of taxa for microbiome studies, which is essentially a combination of taxonomic units. Specifically, we model a genus which consists of a set of OTUs at low hierarchy and is designed to reflect both marginal and joint effects of OTUs associated with the risk of CRC to address these issues. We first demonstrate the power of super-taxon in detecting highly correlated OTUs. Then, we identify CRC-associated OTUs in two publicly available datasets via a discovery-validation procedure. Specifically, four species of two genera are found to be associated with CRC: Parvimonas micra, Parvimonas sp., Peptostreptococcus stomatis, and Peptostreptococcus anaerobius. More importantly, for the first time, we report the joint effect of Parvimonas micra and Parvimonas sp. (p&#x2009;=&#x2009;0.0084) as well as that of Peptostrepto-coccus stomatis and Peptostreptococcus anaerobius (p&#x2009;=&#x2009;8.21e-06) on CRC. The proposed approach provides a novel and useful tool for identifying disease-related microbes by taking the hierarchical structure of taxa into account and further sheds new lights on their potential joint effects as a community in disease development.<br><br>CONCLUSIONS: Our work shows that proposed approaches are effective to study the microbiota-disease relation taking into account for the sparsity, hierarchical and correlated structure among microbes.}, }
@article {pmid35729161, year = {2022}, author = {Zhang, L and Jonscher, KR and Zhang, Z and Xiong, Y and Mueller, RS and Friedman, JE and Pan, C}, title = {Islet autoantibody seroconversion in type-1 diabetes is associated with metagenome-assembled genomes in infant gut microbiomes.}, journal = {Nature communications}, volume = {13}, number = {1}, pages = {3551}, pmid = {35729161}, issn = {2041-1723}, support = {R01 AT011618/AT/NCCIH NIH HHS/United States ; }, mesh = {Autoantibodies ; Child ; *Diabetes Mellitus, Type 1/genetics ; *Gastrointestinal Microbiome/genetics ; Humans ; Infant ; Metagenome/genetics ; Metagenomics/methods ; *Microbiota ; Seroconversion ; }, abstract = {The immune system of some genetically susceptible children can be triggered by certain environmental factors to produce islet autoantibodies (IA) against pancreatic β cells, which greatly increases their risk for Type-1 diabetes. An environmental factor under active investigation is the gut microbiome due to its important role in immune system education. Here, we study gut metagenomes that are de-novo-assembled in 887 at-risk children in the Environmental Determinants of Diabetes in the Young (TEDDY) project. Our results reveal a small set of core protein families, present in >50% of the subjects, which account for 64% of the sequencing reads. Time-series binning generates 21,536 high-quality metagenome-assembled genomes (MAGs) from 883 species, including 176 species that hitherto have no MAG representation in previous comprehensive human microbiome surveys. IA seroconversion is positively associated with 2373 MAGs and negatively with 1549 MAGs. Comparative genomics analysis identifies lipopolysaccharides biosynthesis in Bacteroides MAGs and sulfate reduction in Anaerostipes MAGs as functional signatures of MAGs with positive IA-association. The functional signatures in the MAGs with negative IA-association include carbohydrate degradation in lactic acid bacteria MAGs and nitrate reduction in Escherichia MAGs. Overall, our results show a distinct set of gut microorganisms associated with IA seroconversion and uncovered the functional genomics signatures of these IA-associated microorganisms.}, }
@article {pmid35724423, year = {2022}, author = {Smith, G and Manzano Marín, A and Reyes-Prieto, M and Ribeiro Antunes, CS and Ashworth, V and Goselle, ON and Jan, AAA and Moya, A and Latorre, A and Perotti, MA and Braig, HR}, title = {Human follicular mites: Ectoparasites becoming symbionts.}, journal = {Molecular biology and evolution}, volume = {39}, number = {6}, pages = {}, pmid = {35724423}, issn = {1537-1719}, abstract = {Most humans carry mites in the hair follicles of their skin for their entire lives. Follicular mites are the only metazoans tha continuously live on humans. We propose that Demodex folliculorum (Acari) represents a transitional stage from a host-injuring obligate parasite to an obligate symbiont. Here, we describe the profound impact of this transition on the genome and physiology of the mite. Genome sequencing revealed that the permanent host association of D. folliculorum led to an extensive genome reduction through relaxed selection and genetic drift, resulting in the smallest number of protein-coding genes yet identified among panarthropods. Confocal microscopy revealed that this gene loss coincided with an extreme reduction in the number of cells. Single uninucleate muscle cells are sufficient to operate each of the three segments that form each walking leg. While it has been assumed that the reduction of the cell number in parasites starts early in development, we identified a greater total number of cells in the last developmental stage (nymph) than in the terminal adult stage, suggesting that reduction starts at the adult or ultimate stage of development. This is the first evolutionary step in an arthropod species adopting a reductive, parasitic or endosymbiotic lifestyle. Somatic nuclei show underreplication at the diploid stage. Novel eye structures or photoreceptors as well as a unique human host melatonin-guided day/night rhythm are proposed for the first time. The loss of DNA repair genes coupled with extreme endogamy might have set this mite species on an evolutionary dead-end trajectory.}, }
@article {pmid35724325, year = {2023}, author = {}, title = {Retraction: Human microbiome and homeostasis: Insights into the key role of prebiotics, probiotics, and symbiotics.}, journal = {Critical reviews in food science and nutrition}, volume = {63}, number = {20}, pages = {4817}, doi = {10.1080/10408398.2022.2078104}, pmid = {35724325}, issn = {1549-7852}, }
@article {pmid35723343, year = {2022}, author = {Yoon, YC and Ahn, BH and Min, JW and Lee, KR and Park, SH and Kang, HC}, title = {Stimulatory Effects of Extracellular Vesicles Derived from Leuconostoc holzapfelii That Exists in Human Scalp on Hair Growth in Human Follicle Dermal Papilla Cells.}, journal = {Current issues in molecular biology}, volume = {44}, number = {2}, pages = {845-866}, pmid = {35723343}, issn = {1467-3045}, abstract = {Human hair follicle dermal papilla cells (HFDPCs) located in hair follicles (HFs) play a pivotal role in hair follicle morphogenesis, hair cycling, and hair growth. Over the past few decades, probiotic bacteria (PB) have been reported to have beneficial effects such as improved skin health, anti-obesity, and immuno-modulation for conditions including atopic dermatitis and inflammatory bowel disease (IBD). PB can secrete 50~150 nm sized extracellular vesicles (EVs) containing microbial DNA, miRNA, proteins, lipids, and cell wall components. These EVs can regulate communication between bacteria or between bacteria and their host. Although numerous biological effects of PB-EVs have been reported, the physiological roles of Leuconostoc holzapfelii (hs-Lh), which is isolated from human scalp tissue, and the extracellular vesicles derived from them (hs-LhEVs) are largely unknown. Herein, we investigated the effects of hs-LhEVs on hair growth in HFDPCs. We show that hs-LhEVs increase cell proliferation, migration, and regulate the cell cycle. Furthermore, hs-LhEVs were found to modulate the mRNA expression of hair-growth-related genes in vitro. These data demonstrate that hs-LhEVs can reduce apoptosis by modulating the cell cycle and promote hair growth by regulation via the Wnt/β-catenin signal transduction pathway.}, }
@article {pmid35723322, year = {2022}, author = {Jo, CS and Myung, CH and Yoon, YC and Ahn, BH and Min, JW and Seo, WS and Lee, DH and Kang, HC and Heo, YH and Choi, H and Hong, IK and Hwang, JS}, title = {The Effect of Lactobacillus plantarum Extracellular Vesicles from Korean Women in Their 20s on Skin Aging.}, journal = {Current issues in molecular biology}, volume = {44}, number = {2}, pages = {526-540}, pmid = {35723322}, issn = {1467-3045}, abstract = {Extracellular vesicles, which are highly conserved in most cells, contain biologically active substances. The vesicles and substances interact with cells and impact physiological mechanisms. The skin is the most external organ and is in direct contact with the external environment. Photoaging and skin damage are caused by extrinsic factors. The formation of wrinkles is a major indicator of skin aging and is caused by a decrease in collagen and hyaluronic acid. MMP-1 expression is also increased. Due to accruing damage, skin aging reduces the ability of the skin barrier, thereby lowering the skin's ability to contain water and increasing the amount of water loss. L. plantarum suppresses various harmful bacteria by secreting an antimicrobial substance. L. plantarum is also found in the skin, and research on the interactions between the bacteria and the skin is in progress. Although several studies have investigated L. plantarum, there are only a limited number of studies on extracellular vesicles (EV) derived from L. plantarum, especially in relation to skin aging. Herein, we isolated EVs that were secreted from L. plantarum of women in their 20s (LpEVs). We then investigated the effect of LpEVs on skin aging in CCD986sk. We showed that LpEVs modulated the mRNA expression of ECM related genes in vitro. Furthermore, LpEVs suppressed wrinkle formation and pigmentation in clinical trials. These results demonstrated that LpEVs have a great effect on skin aging by regulating ECM related genes. In addition, our study offers important evidence on the depigmentation effect of LpEVs.}, }
@article {pmid35720372, year = {2022}, author = {Krawczyk, KT and Locht, C and Kowalewicz-Kulbat, M}, title = {Halophilic Archaea Halorhabdus Rudnickae and Natrinema Salaciae Activate Human Dendritic Cells and Orient T Helper Cell Responses.}, journal = {Frontiers in immunology}, volume = {13}, number = {}, pages = {833635}, pmid = {35720372}, issn = {1664-3224}, mesh = {Cytokines ; Dendritic Cells ; *Halobacteriaceae ; Humans ; *Interleukin-13/pharmacology ; T-Lymphocytes, Helper-Inducer ; }, abstract = {Halophilic archaea are procaryotic organisms distinct from bacteria, known to thrive in hypersaline environments, including salt lakes, salterns, brines and salty food. They have also been identified in the human microbiome. The biological significance of halophiles for human health has rarely been examined. The interactions between halophilic archaea and human dendritic cells (DCs) and T cells have not been identified so far. Here, we show for the first time that the halophilic archaea Halorhabdus rudnickae and Natrinema salaciae activate human monocyte-derived DCs, induce DC maturation, cytokine production and autologous T cell activation. In vitro both strains induced DC up-regulation of the cell-surface receptors CD86, CD80 and CD83, and cytokine production, including IL-12p40, IL-10 and TNF-α, but not IL-23 and IL-12p70. Furthermore, autologous CD4[+] T cells produced significantly higher amounts of IFN-γ and IL-13, but not IL-17A when co-cultured with halophile-stimulated DCs in comparison to T cells co-cultured with unstimulated DCs. IFN-γ was almost exclusively produced by naïve T cells, while IL-13 was produced by both naïve and memory CD4[+] T cells. Our findings thus show that halophilic archaea are recognized by human DCs and are able to induce a balanced cytokine response. The immunomodulatory functions of halophilic archaea and their potential ability to re-establish the immune balance may perhaps participate in the beneficial effects of halotherapies.}, }
@article {pmid35718251, year = {2022}, author = {Juarez, VM and Montalbine, AN and Singh, A}, title = {Microbiome as an immune regulator in health, disease, and therapeutics.}, journal = {Advanced drug delivery reviews}, volume = {188}, number = {}, pages = {114400}, pmid = {35718251}, issn = {1872-8294}, support = {/WT_/Wellcome Trust/United Kingdom ; R01 AI132738/AI/NIAID NIH HHS/United States ; R21 AI160136/AI/NIAID NIH HHS/United States ; T32 GM008433/GM/NIGMS NIH HHS/United States ; }, mesh = {Bacteria ; Humans ; *Microbiota/physiology ; *Neoplasms/microbiology ; Pharmaceutical Preparations ; Precision Medicine ; }, abstract = {New discoveries in drugs and drug delivery systems are focused on identifying and delivering a pharmacologically effective agent, potentially targeting a specific molecular component. However, current drug discovery and therapeutic delivery approaches do not necessarily exploit the complex regulatory network of an indispensable microbiota that has been engineered through evolutionary processes in humans or has been altered by environmental exposure or diseases. The human microbiome, in all its complexity, plays an integral role in the maintenance of host functions such as metabolism and immunity. However, dysregulation in this intricate ecosystem has been linked with a variety of diseases, ranging from inflammatory bowel disease to cancer. Therapeutics and bacteria have an undeniable effect on each other and understanding the interplay between microbes and drugs could lead to new therapies, or to changes in how existing drugs are delivered. In addition, targeting the human microbiome using engineered therapeutics has the potential to address global health challenges. Here, we present the challenges and cutting-edge developments in microbiome-immune cell interactions and outline novel targeting strategies to advance drug discovery and therapeutics, which are defining a new era of personalized and precision medicine.}, }
@article {pmid35717467, year = {2022}, author = {Shetty, SA and Kostopoulos, I and Geerlings, SY and Smidt, H and de Vos, WM and Belzer, C}, title = {Dynamic metabolic interactions and trophic roles of human gut microbes identified using a minimal microbiome exhibiting ecological properties.}, journal = {The ISME journal}, volume = {16}, number = {9}, pages = {2144-2159}, pmid = {35717467}, issn = {1751-7370}, support = {NRGWI.obrug.2018.005//Nederlandse Organisatie voor Wetenschappelijk Onderzoek (Netherlands Organisation for Scientific Research)/ ; 024.002.002//Nederlandse Organisatie voor Wetenschappelijk Onderzoek (Netherlands Organisation for Scientific Research)/ ; }, mesh = {Bacteria/genetics ; *Gastrointestinal Microbiome/physiology ; Humans ; *Microbiota ; Mucins ; RNA, Ribosomal, 16S/genetics ; }, abstract = {Microbe-microbe interactions in the human gut are influenced by host-derived glycans and diet. The high complexity of the gut microbiome poses a major challenge for unraveling the metabolic interactions and trophic roles of key microbes. Synthetic minimal microbiomes provide a pragmatic approach to investigate their ecology including metabolic interactions. Here, we rationally designed a synthetic microbiome termed Mucin and Diet based Minimal Microbiome (MDb-MM) by taking into account known physiological features of 16 key bacteria. We combined 16S rRNA gene-based composition analysis, metabolite measurements and metatranscriptomics to investigate community dynamics, stability, inter-species metabolic interactions and their trophic roles. The 16 species co-existed in the in vitro gut ecosystems containing a mixture of complex substrates representing dietary fibers and mucin. The triplicate MDb-MM's followed the Taylor's power law and exhibited strikingly similar ecological and metabolic patterns. The MDb-MM exhibited resistance and resilience to temporal perturbations as evidenced by the abundance and metabolic end products. Microbe-specific temporal dynamics in transcriptional niche overlap and trophic interaction network explained the observed co-existence in a competitive minimal microbiome. Overall, the present study provides crucial insights into the co-existence, metabolic niches and trophic roles of key intestinal microbes in a highly dynamic and competitive in vitro ecosystem.}, }
@article {pmid35713407, year = {2022}, author = {Shaffer, JP and Carpenter, CS and Martino, C and Salido, RA and Minich, JJ and Bryant, M and Sanders, K and Schwartz, T and Humphrey, G and Swafford, AD and Knight, R}, title = {A comparison of six DNA extraction protocols for 16S, ITS and shotgun metagenomic sequencing of microbial communities.}, journal = {BioTechniques}, volume = {73}, number = {1}, pages = {34-46}, pmid = {35713407}, issn = {1940-9818}, support = {R01 DK102932/DK/NIDDK NIH HHS/United States ; K12 GM068524/GM/NIGMS NIH HHS/United States ; U01 AI124316/AI/NIAID NIH HHS/United States ; DP1 AT010885/AT/NCCIH NIH HHS/United States ; U19 AG063744/AG/NIA NIH HHS/United States ; R01 HL140976/HL/NHLBI NIH HHS/United States ; R01 HL134887/HL/NHLBI NIH HHS/United States ; RF1 AG058942/AG/NIA NIH HHS/United States ; }, mesh = {Bacteria/genetics ; High-Throughput Nucleotide Sequencing/methods ; Humans ; *Metagenomics/methods ; *Microbiota/genetics ; Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; }, abstract = {Microbial communities contain a broad phylogenetic diversity of organisms; however, the majority of methods center on describing bacteria and archaea. Fungi are important symbionts in many ecosystems and are potentially important members of the human microbiome, beyond those that can cause disease. To expand our analysis of microbial communities to include data from the fungal internal transcribed spacer (ITS) region, five candidate DNA extraction kits were compared against our standardized protocol for describing bacteria and archaea using 16S rRNA gene amplicon- and shotgun metagenomics sequencing. The results are presented considering a diverse panel of host-associated and environmental sample types and comparing the cost, processing time, well-to-well contamination, DNA yield, limit of detection and microbial community composition among protocols. Across all criteria, the MagMAX Microbiome kit was found to perform best. The PowerSoil Pro kit performed comparably but with increased cost per sample and overall processing time. The Zymo MagBead, NucleoMag Food and Norgen Stool kits were included.}, }
@article {pmid35705822, year = {2022}, author = {Ley, R}, title = {The human microbiome: there is much left to do.}, journal = {Nature}, volume = {606}, number = {7914}, pages = {435}, doi = {10.1038/d41586-022-01610-5}, pmid = {35705822}, issn = {1476-4687}, mesh = {Humans ; *Microbiota ; }, }
@article {pmid35698690, year = {2022}, author = {Anipindi, M and Bitetto, D}, title = {Diagnostic and Therapeutic Uses of the Microbiome in the Field of Oncology.}, journal = {Cureus}, volume = {14}, number = {5}, pages = {e24890}, pmid = {35698690}, issn = {2168-8184}, abstract = {Cancer is a leading cause of death worldwide and it can affect almost every part of the human body. Effective screening and early diagnosis of cancers is extremely difficult due to the multifactorial etiology of the disease and delayed presentation of the patients. The available treatments are usually not specific to the affected organ system, leading to intolerable systemic side effects and early withdrawal from therapies. In vivo and in vitro studies have revealed an association of specific microbiome signatures with individual cancers. The cancer-related human microbiome has also been shown to affect the response of tissues to chemotherapy, immunotherapy, and radiation. This is an excellent opportunity for us to design specific screening markers using the microbiome to prevent cancers and diagnose them early. We can also develop precise treatments that can target cancer-affected specific organ systems and probably use a lesser dose of chemotherapy or radiation for the same effect. This prevents adverse effects and early cessation of treatments. However, we need further studies to exactly clarify and characterize these associations. In this review article, we focus on the association of the microbiome with individual cancers and highlight its future role in cancer screenings, diagnosis, prognosis, and treatments.}, }
@article {pmid35697549, year = {2022}, author = {Droz, L and Jannel, R and Rupprecht, CDD}, title = {Living through multispecies societies: Approaching the microbiome with Imanishi Kinji.}, journal = {Endeavour}, volume = {46}, number = {1-2}, pages = {100814}, doi = {10.1016/j.endeavour.2022.100814}, pmid = {35697549}, issn = {1873-1929}, mesh = {Humans ; *Microbiota ; *Research/classification/trends ; }, abstract = {Recent research about the microbiome points to a picture in which we, humans, are 'living through' nature, and nature itself is living in us. Our bodies are hosting-and depend on-the multiple species that constitute human microbiota. This article will discuss current research on the microbiome through the ideas of Japanese ecologist Imanishi Kinji (1902-1992). First, some of Imanishi's key ideas regarding the world of living beings and multispecies societies are presented. Second, seven types of relationships concerning the human microbiome, human beings, and the environment are explored. Third, inspired by Imanishi's work, this paper develops the idea of dynamic, porous, and complex multispecies societies in which different living beings or species are codependent on others, including microbiota and human beings.}, }
@article {pmid35694384, year = {2022}, author = {Ene, A and Stegman, N and Wolfe, A and Putonti, C}, title = {Genomic insights into Lactobacillus gasseri and Lactobacillus paragasseri.}, journal = {PeerJ}, volume = {10}, number = {}, pages = {e13479}, pmid = {35694384}, issn = {2167-8359}, mesh = {Female ; Humans ; *Lactobacillus gasseri/genetics ; RNA, Ribosomal, 16S/genetics ; Genomics ; Mouth ; Prophages/genetics ; }, abstract = {BACKGROUND: Antimicrobial and antifungal species are essential members of the healthy human microbiota. Several different species of lactobacilli that naturally inhabit the human body have been explored for their probiotic capabilities including strains of the species Lactobacillus gasseri. However, L. gasseri (identified by 16S rRNA gene sequencing) has been associated with urogenital symptoms. Recently a new sister taxon of L. gasseri was described: L. paragasseri. L. paragasseri is also posited to have probiotic qualities.<br><br>METHODS: Here, we present a genomic investigation of all (n&#xa0;=&#xa0;79) publicly available genome assemblies for both species. These strains include isolates from the vaginal tract, gastrointestinal tract, urinary tract, oral cavity, wounds, and lungs.<br><br>RESULTS: The two species cannot be distinguished from short-read sequencing of the 16S rRNA as the full-length gene sequences differ only by two nucleotides. Based upon average nucleotide identity (ANI), we identified 20 strains deposited as L. gasseri that are in fact representatives of L. paragasseri. Investigation of the genic content of the strains of these two species suggests recent divergence and/or frequent gene exchange between the two species. The genomes frequently harbored intact prophage sequences, including prophages identified in strains of both species. To further explore the antimicrobial potential associated with both species, genome assemblies were examined for biosynthetic gene clusters. Gassericin T and S were identified in 46 of the genome assemblies, with all L. paragasseri strains including one or both bacteriocins. This suggests that the properties once ascribed to L. gasseri may better represent the L.&#xa0;paragasseri species.}, }
@article {pmid35693065, year = {2022}, author = {Ozma, MA and Abbasi, A and Akrami, S and Lahouty, M and Shahbazi, N and Ganbarov, K and Pagliano, P and Sabahi, S and Köse, &#x15e; and Yousefi, M and Dao, S and Asgharzadeh, M and Hosseini, H and Kafil, HS}, title = {Postbiotics as the key mediators of the gut microbiota-host interactions.}, journal = {Le infezioni in medicina}, volume = {30}, number = {2}, pages = {180-193}, pmid = {35693065}, issn = {2532-8689}, abstract = {The priority of the Sustainable Development Goals for 2022 is to reduce all causes related to mortality. In this regard, microbial bioactive compounds with characteristics such as optimal compatibility and close interaction with the host immune system are considered a novel therapeutic approach. The fermentation process is one of the most well-known pathways involved in the natural synthesis of a diverse range of postbiotics. However, some postbiotics are a type of probiotic response behavior to environmental stimuli that usually play well-known biological roles. Also, postbiotics with unique structure and function are key mediators between intestinal microbiota and host cellular processes/metabolic pathways that play a significant role in maintaining homeostasis. By further understanding the nature of parent microbial cells, factors affecting their metabolic pathways, and the development of compatible extraction and identification methods, it is possible to achieve certain formulations of postbiotics with special efficiencies, which in turn will significantly improve the performance of health systems (especially in developing countries) toward a wide range of acute/chronic diseases. The present review aims to describe the fundamental role of postbiotics as the key mediators of the microbiota-host interactions. Besides, it presents the available current evidence regarding the interaction between postbiotics and host cells through potential cell receptors, stimulation/improvement of immune system function, and the enhancement of the composition and function of the human microbiome.}, }
@article {pmid35692002, year = {2022}, author = {Song, WJ and Kang, WY and Liu, XM and Sun, L and Feng, Q and Ge, SH}, title = {[Study on the dynamic changes of oral microbiota in type 2 diabetes patients with periodontitis after initial periodontal therapy].}, journal = {Zhonghua kou qiang yi xue za zhi = Zhonghua kouqiang yixue zazhi = Chinese journal of stomatology}, volume = {57}, number = {6}, pages = {585-594}, doi = {10.3760/cma.j.cn112144-20220228-00076}, pmid = {35692002}, issn = {1002-0098}, support = {82170964, 81873716//National Nature Science Foundation of China/ ; ts20190975//The Construction Engineering Special Fund of "Taishan Scholars" of Shandong Province/ ; }, mesh = {Bacteria/genetics ; *Chronic Periodontitis/microbiology/therapy ; *Dental Plaque/microbiology ; *Diabetes Mellitus, Type 2/complications/therapy ; Humans ; *Microbiota ; RNA, Ribosomal, 16S/genetics ; }, abstract = {Objectives: To clarify the effect of initial periodontal therapy on the dynamic changes of oral (saliva, dorsal tongue and subgingival plaque) microbiota in periodontitis patients with or without type 2 diabetes mellitus (T2DM). Methods: A total of 14 patients with chronic periodontitis (CP group) and 14 CP patients with T2DM (CP-T2DM group) were included from Department of Periodontology, School and Hospital of Stomatology,Cheeloo College of Medicine, Shandong University. The microbial samples were collected from saliva, dorsal tongue and subgingival plaque of first molars at baseline, 1.5 and 3 months after initial periodontal therapy, and were detected by 16S rRNA (V3-V4 region) gene sequencing. The sequencing data were analyzed to obtain microbial distribution and community structure information. The same professional periodontist evaluated the periodontal status of patients according to periodontitis detection indices before and after initial periodontal therapy. Meanwhile, patients' blood samples were collected and related metabolic indices were evaluated. Results: After initial periodontal therapy, the glycosylated hemoglobin levels [(7.46±1.69)%] in CP-T2DM group were significantly improved than that at baseline [(7.65±1.34)%] (t=0.52,P=0.610). The probing depth of the sampling sites [CP group: (2.94±0.46) mm, CP-T2DM group: (2.95±0.35) mm] and bleeding index (CP group: 1.91±0.42, CP-T2DM group: 1.67±0.49) at 3 months after treatment were significantly decreased than the probing depth [CP group: (3.99±0.77) mm, CP-T2DM group: (3.80±0.76) mm] (F=25.61, P<0.001; F=17.63, P<0.001) and bleeding index (CP group: 3.03±0.52, CP-T2DM group: 2.54±0.65) (F=28.43, P<0.001; F=20.21, P<0.001) at baseline. The flora analysis showed that the α and β diversity indices of the same sites in the CP and CP-T2DM groups did not change significantly before and after the initial therapy, but the bacterial abundance at each site changed. There were commonalities and differences in the microbial composition of each site in the CP and CP-T2DM groups. Among them, the relative abundance of Proteobacteria in saliva and dorsal tongue samples of the two groups after treatment was basically consistent with the change trend in the subgingival plaque microbes. In the subgingival plaque of the CP group, the relative abundance of Proteobacteria showed a gradual increase with the prolongation of initial periodontal therapy; while in the CP-T2DM group, it showed a trend of first increase and then decrease. Syntrophy, Dethiosulfate, Methanobacteriaceae and TG5 in CP and CP-T2DM groups were all significantly dominant bacteria in subgingival plaque at baseline (P<0.05). Moreover, in the CP-T2DM group Spirochetes also showed a significant advantage. At 1.5 months after treatment, Rhizobacteria, Alcaligenes, Comamomons, Delftia, Blautella, etc. were dominant in subgingival plaque (P<0.05). Firmicutes, Clostridia/Clostridiales, Enterococci and Ruminococci showed significant differences at 3 months (P<0.05). Conclusions: Plaques in saliva and tongue dorsal could reflect the effects of initial periodontal therapy on the dynamic changes of microorganisms to a certain extent. CP and CP-T2DM patients had differences in microbial composition and responses to initial periodontal therapy.}, }
@article {pmid35689685, year = {2023}, author = {Mills, JG and Selway, CA and Thomas, T and Weyrich, LS and Lowe, AJ}, title = {Schoolyard Biodiversity Determines Short-Term Recovery of Disturbed Skin Microbiota in Children.}, journal = {Microbial ecology}, volume = {86}, number = {1}, pages = {658-669}, pmid = {35689685}, issn = {1432-184X}, mesh = {Humans ; Child ; *Microbiota ; Biodiversity ; Forests ; Skin ; }, abstract = {Creating biodiverse urban habitat has been proposed, with growing empirical support, as an intervention for increasing human microbial diversity and reducing associated diseases. However, ecological understanding of urban biodiversity interventions on human skin microbiota remains limited. Here, we experimentally test the hypotheses that disturbed skin microbiota recover better in outdoor schoolyard environments and that greater biodiversity provides a greater response. Repeating the experiment three times, we disturbed skin microbiota of fifty-seven healthy 10-to-11-year-old students with a skin swab (i.e., cleaning), then exposed them to one school environment-either a 'classroom' (n = 20), 'sports field' (n = 14), or biodiverse 'forest' (n = 23)-for 45 min. Another skin swab followed the exposure to compare 'before' and 'after' microbial communities. After 45 min, the disturbance immediately followed by outdoor exposure, especially the 'forest', had an enriching and diversifying effect on skin microbiota, while 'classroom' exposure homogenised inter-personal variability. Each effect compounded over consecutive days indicating longer-term exposure outcomes. The experimental disturbance also reduced the core skin microbiota, and only outdoor environments were able to replenish lost species richness to core membership (n species > 50% prevalent). Overall, we find that environmental setting, especially including biodiversity, is important in human microbiota recovery periods and that the outdoors provide resilience to skin communities. This work also has implications for the inclusion of short periods of outside or forest exposure in school scheduling. Future investigations of the health impacts of permanent urban biodiversity interventions are needed.}, }
@article {pmid35689474, year = {2022}, author = {Diociaiuti, A and Giancristoforo, S and Calò Carducci, FI and Bracaglia, C and Boni, A and Pane, S and Onetti Muda, A and De Benedetti, F and Putignani, L and El Hachem, M}, title = {Auricular leishmaniasis in a child successfully treated with intralesional amphotericin B.}, journal = {Pediatric dermatology}, volume = {39}, number = {5}, pages = {832-833}, pmid = {35689474}, issn = {1525-1470}, mesh = {Amphotericin B/therapeutic use ; *Antiprotozoal Agents/therapeutic use ; Child ; *Ear Auricle ; Family ; Humans ; *Leishmaniasis, Cutaneous/diagnosis/drug therapy ; }, abstract = {Cutaneous leishmaniasis (CL) is the most frequent form of leishmaniasis. The auricle is an extremely rare site for CL in the Old World. Auricular CL may be mistaken for other entities, such as relapsing polychondritis (RP). Here we report a pediatric case of Old World auricular CL mimicking RP in a child successfully treated with intralesional liposomal amphotericin B.}, }
@article {pmid35686484, year = {2022}, author = {Chen, Y and Rudolph, SE and Longo, BN and Pace, F and Roh, TT and Condruti, R and Gee, M and Watnick, PI and Kaplan, DL}, title = {Bioengineered 3D Tissue Model of Intestine Epithelium with Oxygen Gradients to Sustain Human Gut Microbiome.}, journal = {Advanced healthcare materials}, volume = {11}, number = {16}, pages = {e2200447}, pmid = {35686484}, issn = {2192-2659}, support = {P41 EB002520/EB/NIBIB NIH HHS/United States ; P41 EB027062/EB/NIBIB NIH HHS/United States ; S10 OD021624/OD/NIH HHS/United States ; U19 AI131126/AI/NIAID NIH HHS/United States ; }, mesh = {Epithelium ; *Gastrointestinal Microbiome ; Humans ; Intestinal Mucosa ; *Microbiota ; Oxygen ; }, abstract = {The human gut microbiome is crucial to hosting physiology and health. Therefore, stable in vitro coculture of primary human intestinal cells with a microbiome community is essential for understanding intestinal disease progression and revealing novel therapeutic targets. Here, a three-dimensional scaffold system is presented to regenerate an in vitro human intestinal epithelium that recapitulates many functional characteristics of the native small intestines. The epithelium, derived from human intestinal enteroids, contains mature intestinal epithelial cells and possesses selectively permeable barrier functions. Importantly, by properly positioning the scaffolds cultured under normal atmospheric conditions, two physiologically relevant oxygen gradients, a proximal-to-distal oxygen gradient along the gastrointestinal (GI) tract, and a radial oxygen gradient across the epithelium, are distinguished in the tissues when the lumens are faced up and down in cultures, respectively. Furthermore, the presence of the low oxygen gradients supported the coculture of intestinal epithelium along with a complex living commensal gut microbiome (including obligate anaerobes) to simulate temporal microbiome dynamics in the native human gut. This unique silk scaffold platform may enable the exploration of microbiota-related mechanisms of disease pathogenesis and host-pathogen dynamics in infectious diseases including the potential to explore the human microbiome-gut-brain axis and potential novel microbiome-based therapeutics.}, }
@article {pmid35679312, year = {2022}, author = {Wedenoja, S and Saarikivi, A and Mälkönen, J and Leskinen, S and Lehto, M and Adeshara, K and Tuokkola, J and Nikkonen, A and Merras-Salmio, L and Höyhtyä, M and Hörkkö, S and Haaramo, A and Salonen, A and de Vos, WM and Korpela, K and Kolho, KL}, title = {Fecal microbiota in congenital chloride diarrhea and inflammatory bowel disease.}, journal = {PloS one}, volume = {17}, number = {6}, pages = {e0269561}, pmid = {35679312}, issn = {1932-6203}, mesh = {Biomarkers ; Butyrates ; *Crohn Disease/microbiology ; Diarrhea/congenital/genetics ; Feces/microbiology ; Follow-Up Studies ; *Gastrointestinal Microbiome/genetics ; Humans ; *Inflammatory Bowel Diseases/microbiology ; Metabolism, Inborn Errors ; *Microbiota ; Quality of Life ; RNA, Ribosomal, 16S/genetics ; }, abstract = {BACKGROUND AND AIMS: Subjects with congenital chloride diarrhea (CLD; a defect in solute carrier family 26 member 3 (SLC26A3)) are prone to inflammatory bowel disease (IBD). We investigated fecal microbiota in CLD and CLD-associated IBD. We also tested whether microbiota is modulated by supplementation with the short-chain fatty acid butyrate.<br><br>SUBJECTS AND METHODS: We recruited 30 patients with CLD for an observational 3-week follow-up study. Thereafter, 16 consented to oral butyrate substitution for a 3-week observational period. Fecal samples, collected once a week, were assayed for calprotectin and potential markers of inflammation, and studied by 16S ribosomal ribonucleic acid (rRNA) gene amplicon sequencing and compared to that of 19 healthy controls and 43 controls with Crohn's disease. Data on intestinal symptoms, diet and quality of life were collected.<br><br>RESULTS: Patients with CLD had increased abundances of Proteobacteria, Veillonella, and Prevotella, and lower abundances of normally dominant taxa Ruminococcaceae and Lachnospiraceae when compared with healthy controls and Crohn&#xb4;s disease. No major differences in fecal microbiota were found between CLD and CLD-associated IBD (including two with yet untreated IBD). Butyrate was poorly tolerated and showed no major effects on fecal microbiota or biomarkers in CLD.<br><br>CONCLUSIONS: Fecal microbiota in CLD is different from that of healthy subjects or Crohn&#xb4;s disease. Unexpectedly, no changes in the microbiota or fecal markers characterized CLD-associated IBD, an entity with high frequency among patients with CLD.}, }
@article {pmid35678287, year = {2022}, author = {Hou, Y and Tan, T and Guo, Z and Ji, Y and Hu, J and Zhang, Y}, title = {Gram-selective antibacterial peptide hydrogels.}, journal = {Biomaterials science}, volume = {10}, number = {14}, pages = {3831-3844}, doi = {10.1039/d2bm00558a}, pmid = {35678287}, issn = {2047-4849}, mesh = {Animals ; Humans ; Mice ; *Anti-Bacterial Agents/chemistry/pharmacology ; *Gram-Negative Bacteria ; Gram-Positive Bacteria ; Hydrogels/chemistry/pharmacology ; Microbial Sensitivity Tests ; Peptides ; }, abstract = {The human microbiome plays fundamental roles in human health and disease. However, widely used broad-spectrum antibiotics severely disrupt human-related microbial communities, eventually leading to resistant bacteria, posing a growing threat to global medical health. Antimicrobial peptides (AMPs) are promising antimicrobial agents that barely cause bacterial resistance. Excellent broad-spectrum antimicrobial activities have been achieved using hydrogels self-assembled from AMPs, but there is still a lack of AMP hydrogels that can target Gram-positive and Gram-negative bacteria. Herein, several hydrogels self-assembled from AMPs, termed IK1, IK3, and IK4, were designed and synthesized. In vitro antibacterial results indicated that the IK1 and IK4 hydrogels specifically targeted Gram-positive and Gram-negative bacteria, respectively, while the IK3 hydrogel targeted both Gram-positive and Gram-negative bacteria. The desired broad-spectrum or Gram-selective AMP hydrogels are believed to be obtained through the rational design of the hydrophilicity, hydrophobicity, and charge properties of the peptide molecules. Good in vivo Gram-selective antibacterial properties and the ability to promote wound healing have been demonstrated via treating mouse wound models with these AMP hydrogels. We believe that these Gram-selective AMP hydrogels could potentially have important applications in treating common recurring infections.}, }
@article {pmid35676823, year = {2023}, author = {Dedrick, RM and Smith, BE and Cristinziano, M and Freeman, KG and Jacobs-Sera, D and Belessis, Y and Whitney Brown, A and Cohen, KA and Davidson, RM and van Duin, D and Gainey, A and Garcia, CB and Robert George, CR and Haidar, G and Ip, W and Iredell, J and Khatami, A and Little, JS and Malmivaara, K and McMullan, BJ and Michalik, DE and Moscatelli, A and Nick, JA and Tupayachi Ortiz, MG and Polenakovik, HM and Robinson, PD and Skurnik, M and Solomon, DA and Soothill, J and Spencer, H and Wark, P and Worth, A and Schooley, RT and Benson, CA and Hatfull, GF}, title = {Phage Therapy of Mycobacterium Infections: Compassionate Use of Phages in 20 Patients With Drug-Resistant Mycobacterial Disease.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {76}, number = {1}, pages = {103-112}, pmid = {35676823}, issn = {1537-6591}, support = {K08 HL139994/HL/NHLBI NIH HHS/United States ; R01 HL090991/HL/NHLBI NIH HHS/United States ; R01 HL146228/HL/NHLBI NIH HHS/United States ; R35 GM131729/GM/NIGMS NIH HHS/United States ; }, mesh = {Humans ; Compassionate Use Trials ; *Phage Therapy ; *Bacteriophages ; Pharmaceutical Preparations ; *Mycobacterium ; *Mycobacterium Infections, Nontuberculous/microbiology ; *Cystic Fibrosis/microbiology ; Anti-Bacterial Agents/therapeutic use ; }, abstract = {BACKGROUND: Nontuberculous Mycobacterium infections, particularly Mycobacterium abscessus, are increasingly common among patients with cystic fibrosis and chronic bronchiectatic lung diseases. Treatment is challenging due to intrinsic antibiotic resistance. Bacteriophage therapy represents a potentially novel approach. Relatively few active lytic phages are available and there is great variation in phage susceptibilities among M. abscessus isolates, requiring personalized phage identification.<br><br>METHODS: Mycobacterium isolates from 200 culture-positive patients with symptomatic disease were screened for phage susceptibilities. One or more lytic phages were identified for 55 isolates. Phages were administered intravenously, by aerosolization, or both to 20 patients on a compassionate use basis and patients were monitored for adverse reactions, clinical and microbiologic responses, the emergence of phage resistance, and phage neutralization in serum, sputum, or bronchoalveolar lavage fluid.<br><br>RESULTS: No adverse reactions attributed to therapy were seen in any patient regardless of the pathogen, phages administered, or the route of delivery. Favorable clinical or microbiological responses were observed in 11 patients. Neutralizing antibodies were identified in serum after initiation of phage delivery intravenously in 8 patients, potentially contributing to lack of treatment response in 4 cases, but were not consistently associated with unfavorable responses in others. Eleven patients were treated with only a single phage, and no phage resistance was observed in any of these.<br><br>CONCLUSIONS: Phage treatment of Mycobacterium infections is challenging due to the limited repertoire of therapeutically useful phages, but favorable clinical outcomes in patients lacking any other treatment options support continued development of adjunctive phage therapy for some mycobacterial infections.}, }
@article {pmid35672071, year = {2022}, author = {Shahzad, M and Andrews, SC and Ul-Haq, Z}, title = {Exploring the role of Microbiome in Susceptibility, Treatment Response and Outcome among Tuberculosis Patients from Pakistan: study protocol for a prospective cohort study (Micro-STOP).}, journal = {BMJ open}, volume = {12}, number = {6}, pages = {e058463}, pmid = {35672071}, issn = {2044-6055}, mesh = {Case-Control Studies ; Cohort Studies ; Humans ; *Microbiota ; Pakistan ; Prospective Studies ; *Tuberculosis/drug therapy ; }, abstract = {INTRODUCTION: Tuberculosis (TB) caused by Mycobacterium tuberculosis is a common infectious disease associated with significant morbidity and mortality, especially in low-income and middle-income countries. Successful treatment of the disease requires prolonged intake (6-8 months) of multiple antibiotics with potentially detrimental consequences on the composition and functional potential of the human microbiome. The protocol described in the current study aims to identify microbiome (oral and gut) signatures associated with TB pathogenesis, treatment response and outcome in humans.<br><br>METHODS AND ANALYSIS: Four hundred and fifty, newly diagnosed patients with TB from three district levels (Peshawar, Mardan and Swat) TB diagnosis and treatment centres, will be recruited in this non-interventional, prospective cohort study and will be followed and monitored until treatment completion. Demographic and dietary intake data, anthropometric measurement and blood, stool and salivary rinse samples will be collected at baseline, day 15, month-2 and end of the treatment. Additionally, we will recruit age (&#xb1;3 years) and sex-matched healthy controls (n=30). Blood sampling will allow monitoring of the immune response during the treatment, while salivary rinse and faecal samples will allow monitoring of dynamic changes in oral and gut microbiome diversity. Within this prospective cohort study, a nested case-control study design will be conducted to assess perturbations in oral and gut microbiome diversity (microbial dysbiosis) and immune response and compare between the patients groups (treatment success vs failure).<br><br>ETHICS AND DISSEMINATION: The study has received ethics approval from the Ethic Board of Khyber Medical University Peshawar, and administrative approval from Provincial TB Control Programme of Khyber Pakhtunkhwa, Pakistan. The study results will be presented in national and international conferences and published in peer-reviewed journals.<br><br>TRIAL REGISTRATION NUMBER: NCT04985994.}, }
@article {pmid35668366, year = {2022}, author = {Girgis, HZ}, title = {MeShClust v3.0: high-quality clustering of DNA sequences using the mean shift algorithm and alignment-free identity scores.}, journal = {BMC genomics}, volume = {23}, number = {1}, pages = {423}, pmid = {35668366}, issn = {1471-2164}, mesh = {*Algorithms ; Base Sequence ; Cluster Analysis ; Computational Biology ; Humans ; *Microbiota ; Software ; }, abstract = {BACKGROUND: Tools for accurately clustering biological sequences are among the most important tools in computational biology. Two pioneering tools for clustering sequences are CD-HIT and UCLUST, both of which are fast and consume reasonable amounts of memory; however, there is a big room for improvement in terms of cluster quality. Motivated by this opportunity for improving cluster quality, we applied the mean shift algorithm in MeShClust v1.0. The mean shift algorithm is an instance of unsupervised learning. Its strong theoretical foundation guarantees the convergence to the true cluster centers. Our implementation of the mean shift algorithm in MeShClust v1.0 was a step forward. In this work, we scale up the algorithm by adapting an out-of-core strategy while utilizing alignment-free identity scores in a new tool: MeShClust v3.0.<br><br>RESULTS: We evaluated CD-HIT, MeShClust v1.0, MeShClust v3.0, and UCLUST on 22 synthetic sets and five real sets. These data sets were designed or selected for testing the tools in terms of scalability and different similarity levels among sequences comprising clusters. On the synthetic data sets, MeShClust v3.0 outperformed the related tools on all sets in terms of cluster quality. On two real data sets obtained from human microbiome and maize transposons, MeShClust v3.0 outperformed the related tools by wide margins, achieving 55%-300% improvement in cluster quality. On another set that includes degenerate viral sequences, MeShClust v3.0 came third. On two bacterial sets, MeShClust v3.0 was the only applicable tool because of the long sequences in these sets. MeShClust v3.0 requires more time and memory than the related tools; almost all personal computers at the time of this writing can accommodate such requirements. MeShClust v3.0 can estimate an important parameter that controls cluster membership with high accuracy.<br><br>CONCLUSIONS: These results demonstrate the high quality of clusters produced by MeShClust v3.0 and its ability to apply the mean shift algorithm to large data sets and long sequences. Because clustering tools are utilized in many studies, providing high-quality clusters will help with deriving accurate biological knowledge.}, }
@article {pmid35665543, year = {2022}, author = {Chueachavalit, C and Meephansan, J and Payungporn, S and Sawaswong, V and Chanchaem, P and Wongpiyabovorn, J and Thio, HB}, title = {Comparison of Malassezia spp. colonization between human skin exposed to high- and low-ambient air pollution.}, journal = {Experimental dermatology}, volume = {31}, number = {9}, pages = {1454-1461}, doi = {10.1111/exd.14622}, pmid = {35665543}, issn = {1600-0625}, mesh = {*Air Pollution/adverse effects ; Dysbiosis ; Humans ; *Malassezia ; *Microbiota ; Skin/microbiology ; }, abstract = {The skin microbiota is essential for human health; altered skin microbiome colonization and homeostasis may be associated with several inflammatory skin conditions and other inflammatory diseases. Malassezia spp. are commensal fungi commonly found on the human skin, and they also play a pathogenic role in various skin diseases. It is hypothesized that the exposure of human skin to air pollution might be associated with Malassezia spp. colonization. The aim of this study was to compare Malassezia spp. colonization on healthy human skin between people living in two major cities in Thailand with different air qualities: one city with highly polluted ambient air and the other with less polluted air. Skin microbiome samples from 66 participants were collected using swabbing and scraping techniques. The skin fungal composition was analysed using high-throughput sequencing based on internal transcribed spacer 2 (ITS2) rDNA. A significant difference was found in alpha and beta diversities and the relative abundance of fungal profiles between the groups. The relative abundance of Malassezia spp. was found to be significantly higher in the highly polluted area than in the less polluted area. This study demonstrates that high-ambient air pollution may alter Malassezia spp. colonization on healthy human skin, which could lead to dysbiosis of the cutaneous ecosystem and eventually result in some skin disorders.}, }
@article {pmid35664318, year = {2022}, author = {Chen, Q and Lin, S and Song, C}, title = {An Adaptive and Robust Test for Microbial Community Analysis.}, journal = {Frontiers in genetics}, volume = {13}, number = {}, pages = {846258}, pmid = {35664318}, issn = {1664-8021}, abstract = {In microbiome studies, researchers measure the abundance of each operational taxon unit (OTU) and are often interested in testing the association between the microbiota and the clinical outcome while conditional on certain covariates. Two types of approaches exists for this testing purpose: the OTU-level tests that assess the association between each OTU and the outcome, and the community-level tests that examine the microbial community all together. It is of considerable interest to develop methods that enjoy both the flexibility of OTU-level tests and the biological relevance of community-level tests. We proposed MiAF, a method that adaptively combines p-values from the OTU-level tests to construct a community-level test. By borrowing the flexibility of OTU-level tests, the proposed method has great potential to generate a series of community-level tests that suit a range of different microbiome profiles, while achieving the desirable high statistical power of community-level testing methods. Using simulation study and real data applications in a smoker throat microbiome study and a HIV patient stool microbiome study, we demonstrated that MiAF has comparable or better power than methods that are specifically designed for community-level tests. The proposed method also provides a natural heuristic taxa selection.}, }
@article {pmid35664224, year = {2022}, author = {Wang, L and Zhang, W and Wu, X and Liang, X and Cao, L and Zhai, J and Yang, Y and Chen, Q and Liu, H and Zhang, J and Ding, Y and Zhu, F and Tang, J}, title = {MIAOME: Human microbiome affect the host epigenome.}, journal = {Computational and structural biotechnology journal}, volume = {20}, number = {}, pages = {2455-2463}, pmid = {35664224}, issn = {2001-0370}, abstract = {Besides the genetic factors having tremendous influences on the regulations of the epigenome, the microenvironmental factors have recently gained extensive attention for their roles in affecting the host epigenome. There are three major types of microenvironmental factors: microbiota-derived metabolites (MDM), microbiota-derived components (MDC) and microbiota-secreted proteins (MSP). These factors can regulate host physiology by modifying host gene expression through the three highly interconnected epigenetic mechanisms (e.g. histone modifications, DNA modifications, and non-coding RNAs). However, no database was available to provide the comprehensive factors of these types. Herein, a database entitled 'Human Microbiome Affect The Host Epigenome (MIAOME)' was constructed. Based on the types of epigenetic modifications confirmed in the literature review, the MIAOME database captures 1068 (63 genus, 281 species, 707 strains, etc.) human microbes, 91 unique microbiota-derived metabolites &amp; components (16 fatty acids, 10 bile acids, 10 phenolic compounds, 10 vitamins, 9 tryptophan metabolites, etc.) derived from 967 microbes; 50 microbes that secreted 40 proteins; 98 microbes that directly influence the host epigenetic modification, and provides 3 classifications of the epigenome, including (1) 4 types of DNA modifications, (2) 20 histone modifications and (3) 490 ncRNAs regulations, involved in 160 human diseases. All in all, MIAOME has compiled the information on the microenvironmental factors influence host epigenome through the scientific literature and biochemical databases, and allows the collective considerations among the different types of factors. It can be freely assessed without login requirement by all users at: http://miaome.idrblab.net/ttd/.}, }
@article {pmid35661736, year = {2022}, author = {Cohen, LJ and Han, SM and Lau, P and Guisado, D and Liang, Y and Nakashige, TG and Ali, T and Chiang, D and Rahman, A and Brady, SF}, title = {Unraveling function and diversity of bacterial lectins in the human microbiome.}, journal = {Nature communications}, volume = {13}, number = {1}, pages = {3101}, pmid = {35661736}, issn = {2041-1723}, support = {K08 DK109287/DK/NIDDK NIH HHS/United States ; P41 GM103694/GM/NIGMS NIH HHS/United States ; R01 AT009562/AT/NCCIH NIH HHS/United States ; R35 GM122559/GM/NIGMS NIH HHS/United States ; R24 GM098791/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Bacteria/metabolism ; Humans ; *Lectins/metabolism ; Mice ; *Microbiota ; Plants/metabolism ; }, abstract = {The mechanisms by which commensal organisms affect human physiology remain poorly understood. Lectins are non-enzymatic carbohydrate binding proteins that all organisms employ as part of establishing a niche, evading host-defenses and protecting against pathogens. Although lectins have been extensively studied in plants, bacterial pathogens and human immune cells for their role in disease pathophysiology and as therapeutics, the role of bacterial lectins in the human microbiome is largely unexplored. Here we report on the characterization of a lectin produced by a common human associated bacterium that interacts with myeloid cells in the blood and intestine. In mouse and cell-based models, we demonstrate that this lectin induces distinct immunologic responses in peripheral and intestinal leukocytes and that these responses are specific to monocytes, macrophages and dendritic cells. Our analysis of human microbiota sequencing data reveal thousands of unique sequences that are predicted to encode lectins, many of which are highly prevalent in the human microbiome yet completely uncharacterized. Based on the varied domain architectures of these lectins we predict they will have diverse effects on the human host. The systematic investigation of lectins in the human microbiome should improve our understanding of human health and provide new therapeutic opportunities.}, }
@article {pmid35659718, year = {2022}, author = {Almand, AT and Anderson, AP and Hitt, BD and Sitko, JC and Joy, RM and Easter, BD and Almand, EA}, title = {The influence of perceived stress on the human microbiome.}, journal = {BMC research notes}, volume = {15}, number = {1}, pages = {193}, pmid = {35659718}, issn = {1756-0500}, mesh = {Dysbiosis ; Feces ; *Gastrointestinal Microbiome ; Humans ; *Microbiota ; RNA, Ribosomal, 16S ; Stress, Psychological ; }, abstract = {OBJECTIVE: Microbial dysbiosis, a shift from commensal to pathogenic microbiota, is often associated with mental health and the gut-brain axis, where dysbiosis in the gut may be linked to dysfunction in the brain. Many studies focus on dysbiosis induced by clinical events or traumatic incidents; however, many professions in austere or demanding environments may encounter continuously compounded stressors. This study seeks to explore the relationship between microbial populations and stress, both perceived and biochemical.<br><br>RESULTS: Eight individuals enrolled in the study to provide a longitudinal assessment of the impact of stress on gut health, with four individuals providing enough samples for analysis. Eleven core microbial genera were identified, although the relative abundance of these genera and other members of the microbial population shifted over time. Although our results indicate a potential relationship between perceived stress and microbial composition of the gut, no association with biochemical stress was observed. Increases in perceived stress seem to elucidate a change in potentially beneficial Bacteroides, with a loss in Firmicutes phyla. This shift occurred in multiple individuals, whereas using cortisol as a stress biomarker showed contradictory responses. These preliminary data provide a potential mechanism for gut monitoring, while identifying targets for downstream modulation.}, }
@article {pmid35658516, year = {2022}, author = {Naud, S and Ibrahim, A and Valles, C and Maatouk, M and Bittar, F and Tidjani Alou, M and Raoult, D}, title = {Candidate Phyla Radiation, an Underappreciated Division of the Human Microbiome, and Its Impact on Health and Disease.}, journal = {Clinical microbiology reviews}, volume = {35}, number = {3}, pages = {e0014021}, pmid = {35658516}, issn = {1098-6618}, mesh = {Bacteria ; Dysbiosis ; Humans ; *Microbiota ; Mouth/microbiology ; }, abstract = {Candidate phyla radiation (CPR) is an emerging division of the bacterial domain within the human microbiota. Still poorly known, these microorganisms were first described in the environment in 1981 as "ultramicrobacteria" with a cell volume under 0.1 μm[3] and were first associated with the human oral microbiota in 2007. The evolution of technology has been paramount for the study of CPR within the human microbiota. In fact, since these ultramicrobacteria have yet to be axenically cultured despite ongoing efforts, progress in imaging technology has allowed their observation and morphological description. Although their genomic abilities and taxonomy are still being studied, great strides have been made regarding their taxonomic classification, as well as their lifestyle. In addition, advancements in next-generation sequencing and the continued development of bioinformatics tools have allowed their detection as commensals in different human habitats, including the oral cavity and gastrointestinal and genital tracts, thus highlighting CPR as a nonnegligible part of the human microbiota with an impact on physiological settings. Conversely, several pathologies present dysbiosis affecting CPR levels, including inflammatory, mucosal, and infectious diseases. In this exhaustive review of the literature, we provide a historical perspective on the study of CPR, an overview of the methods available to study these organisms and a description of their taxonomy and lifestyle. In addition, their distribution in the human microbiome is presented in both homeostatic and dysbiotic settings. Future efforts should focus on developing cocultures and, if possible, axenic cultures to obtain isolates and therefore genomes that would provide a better understanding of these ultramicrobacteria, the importance of which in the human microbiome is undeniable.}, }
@article {pmid35654877, year = {2022}, author = {Stockdale, SR and Harrington, RS and Shkoporov, AN and Khokhlova, EV and Daly, KM and McDonnell, SA and O'Reagan, O and Nolan, JA and Sheehan, D and Lavelle, A and Draper, LA and Shanahan, F and Ross, RP and Hill, C}, title = {Metagenomic assembled plasmids of the human microbiome vary across disease cohorts.}, journal = {Scientific reports}, volume = {12}, number = {1}, pages = {9212}, pmid = {35654877}, issn = {2045-2322}, mesh = {Humans ; *Inflammatory Bowel Diseases/genetics/microbiology ; Metagenome ; Metagenomics ; *Microbiota ; Plasmids/genetics ; }, abstract = {We compiled a human metagenome assembled plasmid (MAP) database and interrogated differences across multiple studies that were originally designed to investigate the composition of the human microbiome across various lifestyles, life stages and events. This was performed as plasmids enable bacteria to rapidly expand their functional capacity through mobilisation, yet their contribution to human health and disease is poorly understood. We observed that inter-sample β-diversity differences of plasmid content (plasmidome) could distinguish cohorts across a multitude of conditions. We also show that reduced intra-sample plasmidome α-diversity is consistent amongst patients with inflammatory bowel disease (IBD) and Clostridioides difficile infections. We also show that faecal microbiota transplants can restore plasmidome diversity. Overall plasmidome diversity, specific plasmids, and plasmid-encoded functions can all potentially act as biomarkers of IBD or its severity. The human plasmidome is an overlooked facet of the microbiome and should be integrated into investigations regarding the role of the microbiome in promoting health or disease. Including MAP databases in analyses will enable a greater understanding of the roles of plasmid-encoded functions within the gut microbiome and will inform future human metagenome analyses.}, }
@article {pmid35654142, year = {2022}, author = {Bhoite, SS and Han, Y and Ruotolo, BT and Chapman, MR}, title = {Mechanistic insights into accelerated α-synuclein aggregation mediated by human microbiome-associated functional amyloids.}, journal = {The Journal of biological chemistry}, volume = {298}, number = {7}, pages = {102088}, pmid = {35654142}, issn = {1083-351X}, support = {R01 GM118651/GM/NIGMS NIH HHS/United States ; }, mesh = {*Amyloid/metabolism ; Animals ; Escherichia coli ; *Escherichia coli Proteins/metabolism ; Humans ; Mice ; *Microbiota ; Parkinson Disease/pathology ; *Protein Aggregation, Pathological ; *alpha-Synuclein/metabolism ; }, abstract = {The gut microbiome has been shown to have key implications in the pathogenesis of Parkinson's disease (PD). The Escherichia coli functional amyloid CsgA is known to accelerate α-synuclein aggregation in vitro and induce PD symptoms in mice. However, the mechanism governing CsgA-mediated acceleration of α-synuclein aggregation is unclear. Here, we show that CsgA can form stable homodimeric species that correlate with faster α-synuclein amyloid aggregation. Furthermore, we identify and characterize new CsgA homologs encoded by bacteria present in the human microbiome. These CsgA homologs display diverse aggregation kinetics, and they differ in their ability to modulate α-synuclein aggregation. Remarkably, we demonstrate that slowing down CsgA aggregation leads to an increased acceleration of α-synuclein aggregation, suggesting that the intrinsic amyloidogenicity of gut bacterial CsgA homologs affects their ability to accelerate α-synuclein aggregation. Finally, we identify a complex between CsgA and α-synuclein that functions as a platform to accelerate α-synuclein aggregation. Taken together, our work reveals complex interplay between bacterial amyloids and α-synuclein that better informs our understanding of PD causation.}, }
@article {pmid35650275, year = {2022}, author = {Pausan, MR and Blohs, M and Mahnert, A and Moissl-Eichinger, C}, title = {The sanitary indoor environment-a potential source for intact human-associated anaerobes.}, journal = {NPJ biofilms and microbiomes}, volume = {8}, number = {1}, pages = {44}, pmid = {35650275}, issn = {2055-5008}, support = {P 30796/FWF_/Austrian Science Fund FWF/Austria ; P 32697/FWF_/Austrian Science Fund FWF/Austria ; }, mesh = {Archaea/genetics ; Humans ; *Microbiota/genetics ; Oxygen ; RNA, Ribosomal, 16S/genetics ; Symbiosis ; }, abstract = {A healthy human microbiome relies on the interaction with and exchange of microbes that takes place between the human body and its environment. People in high-income countries spend most of their time indoors and for this reason, the built environment (BE) might represent a potent source of commensal microbes. Anaerobic microbes are of particular interest, as researchers have not yet sufficiently clarified how the human microbiome acquires oxygen-sensitive microbes. We sampled the bathrooms in ten households and used propidium monoazide (PMA) to assess the viability of the collected prokaryotes. We compared the microbiome profiles based on 16S rRNA gene sequencing and confirmed our results by genetic and cultivation-based analyses. Quantitative and qualitative analysis revealed that most of the microbial taxa in the BE samples are human-associated. Less than 25% of the prokaryotic signatures originate from intact cells, indicating that aerobic and stress resistant taxa display an apparent survival advantage. However, we also confirmed the presence of intact, strictly anaerobic taxa on bathroom floors, including methanogenic archaea. As methanogens are regarded as highly sensitive to aerobic conditions, oxygen-tolerance experiments were performed with human-associated isolates to validate their survival. These results show that human-associated methanogens can survive oxic conditions for at least 6 h. We collected strong evidence that supports the hypothesis that obligate anaerobic taxa can survive in the BE for a limited amount of time. This suggests that the BE serves as a potential source of anaerobic human commensals.}, }
@article {pmid35643079, year = {2022}, author = {Guthrie, L and Spencer, SP and Perelman, D and Van Treuren, W and Han, S and Yu, FB and Sonnenburg, ED and Fischbach, MA and Meyer, TW and Sonnenburg, JL}, title = {Impact of a 7-day homogeneous diet on interpersonal variation in human gut microbiomes and metabolomes.}, journal = {Cell host &amp; microbe}, volume = {30}, number = {6}, pages = {863-874.e4}, pmid = {35643079}, issn = {1934-6069}, support = {R01 DK101674/DK/NIDDK NIH HHS/United States ; P01 HL147823/HL/NHLBI NIH HHS/United States ; R01 DK085025/DK/NIDDK NIH HHS/United States ; T32 DK007056/DK/NIDDK NIH HHS/United States ; F32 AG062119/AG/NIA NIH HHS/United States ; T32 AI007328/AI/NIAID NIH HHS/United States ; P30 DK020579/DK/NIDDK NIH HHS/United States ; }, mesh = {Diet ; *Gastrointestinal Microbiome ; Humans ; Indican ; Metabolome ; *Microbiota ; }, abstract = {Gut microbiota metabolism of dietary compounds generates a vast array of microbiome-dependent metabolites (MDMs), which are highly variable between individuals. The uremic MDMs (uMDMs) phenylacetylglutamine (PAG), p-cresol sulfate (PCS), and indoxyl sulfate (IS) accumulate during renal failure and are associated with poor outcomes. Targeted dietary interventions may reduce toxic MDM generation; however, it is unclear if inter-individual differences in diet or gut microbiome dominantly contribute to MDM variance. Here, we use a 7-day homogeneous average American diet to standardize dietary precursor availability in 21 healthy individuals. During dietary homogeneity, the coefficient of variation in PAG, PCS, and IS (primary outcome) did not decrease, nor did inter-individual variation in most identified metabolites; other microbiome metrics showed no or modest responses to the intervention. Host identity and age are dominant contributors to variability in MDMs. These results highlight the potential need to pair dietary modification with microbial therapies to control MDM profiles.}, }
@article {pmid35641786, year = {2022}, author = {Cani, PD and Depommier, C and Derrien, M and Everard, A and de Vos, WM}, title = {Akkermansia muciniphila: paradigm for next-generation beneficial microorganisms.}, journal = {Nature reviews. Gastroenterology &amp; hepatology}, volume = {19}, number = {10}, pages = {625-637}, pmid = {35641786}, issn = {1759-5053}, mesh = {*Akkermansia ; Animals ; Humans ; Intestines/microbiology ; Obesity/microbiology ; *Verrucomicrobia/physiology ; }, abstract = {Ever since Akkermansia muciniphila was discovered and characterized two decades ago, numerous studies have shown that the lack or decreased abundance of this commensal bacterium was linked with multiple diseases (such as obesity, diabetes, liver steatosis, inflammation and response to cancer immunotherapies). Although primarily based on simple associations, there are nowadays an increasing number of studies moving from correlations to causality. The causal evidence derived from a variety of animal models performed in different laboratories and recently was also recapitulated in a human proof-of-concept trial. In this Review, we cover the history of the discovery of A. muciniphila and summarize the numerous findings and main mechanisms of action by which this intestinal symbiont improves health. A comparison of this microorganism with other next-generation beneficial microorganisms that are being developed is also made.}, }
@article {pmid35638779, year = {2022}, author = {Attai, H and Wilde, J and Liu, R and Chopyk, J and Garcia, AG and Allen-Vercoe, E and Pride, D}, title = {Bacteriophage-Mediated Perturbation of Defined Bacterial Communities in an In Vitro Model of the Human Gut.}, journal = {Microbiology spectrum}, volume = {10}, number = {3}, pages = {e0113522}, pmid = {35638779}, issn = {2165-0497}, mesh = {Animals ; Bacteria ; *Bacteriophages ; Bacteroidetes ; Feces/microbiology ; Gastrointestinal Tract/microbiology ; Humans ; Mice ; *Microbiota ; *Viruses ; }, abstract = {The study of bacteriophage communities reproducing in the gastrointestinal tract is limited by the quality of model systems supporting experimental manipulation in vitro. Traditionally, studies aiming to experimentally address phage-bacteria dynamics have utilized gnotobiotic mice inoculated with defined bacterial communities. While mouse models simulate complex interactions between microbes and their host, they also forestall the study of phage-bacteria dynamics in isolation of host factors. Here, we established a method for manipulating phage-bacteria dynamics using an in vitro chemostat bioreactor model of the distal human gut. We create defined communities representing a subset of bacteria in the feces of two human individuals, cultivated these communities in chemostat bioreactors, developed methods to purify the autochthonous viromes associated with each cultured community, and trialed a system for transmitting live or heat-killed viruses between chemostat bioreactors to decipher outcomes of virus-mediated perturbation. We found that allochthonous viromes were detectable via metagenomic sequencing against the autochthonous virome background and that shifts in bacterial community diversity and composition were detectable in relation to time posttreatment. These microbiome composition changes spanned multiple phyla, including Bacteroidetes, Firmicutes, and Actinobacteria. We also found that compositional changes occurred when using live viruses regardless of whether intrasubject or intersubject viruses were used as the perturbation agents. Our results supported the use of chemostat bioreactors as a platform for studying complex bacteria-phage dynamics in vitro. IMPORTANCE Bacteriophages are relatively ubiquitous in the environment and are highly abundant in the human microbiome. Phages can be commonly transmitted between close contacts, but the impact that such transmissions may have on their bacteria counterparts in our microbiomes is unknown. We developed a chemostat cultivation system to simulate individual-specific features of human distal gut microbiota that can be used to transmit phages between ecosystems and measure their impacts on the microbiota. We used this system to transfer phage communities between chemostats that represented different human subjects. We found that there were significant effects on overall microbiota diversity and changes in the relative abundances of Bacteroidetes, Firmicutes, and Actinobacteria, when intersubject perturbations were performed, compared to intrasubject perturbations. These changes were observed when perturbations were performed using live phages, but not when heat-killed phages were used, and they support the use of chemostat systems for studying complex human bacteria-phage dynamics.}, }
@article {pmid35636654, year = {2022}, author = {Bryan, NS and Burleigh, MC and Easton, C}, title = {The oral microbiome, nitric oxide and exercise performance.}, journal = {Nitric oxide : biology and chemistry}, volume = {125-126}, number = {}, pages = {23-30}, doi = {10.1016/j.niox.2022.05.004}, pmid = {35636654}, issn = {1089-8611}, mesh = {Bacteria/metabolism ; Exercise ; Humans ; *Microbiota ; Nitrates/metabolism ; Nitric Oxide/metabolism ; *Nitrites/metabolism ; Nitrogen Oxides/metabolism ; }, abstract = {The human microbiome comprises ∼10[13]-10[14] microbial cells which form a symbiotic relationship with the host and play a critical role in the regulation of human metabolism. In the oral cavity, several species of bacteria are capable of reducing nitrate to nitrite; a key precursor of the signaling molecule nitric oxide. Nitric oxide has myriad physiological functions, which include the maintenance of cardiovascular homeostasis and the regulation of acute and chronic responses to exercise. This article provides a brief narrative review of the research that has explored how diversity and plasticity of the oral microbiome influences nitric oxide bioavailability and related physiological outcomes. There is unequivocal evidence that dysbiosis (e.g. through disease) or disruption (e.g. by use of antiseptic mouthwash or antibiotics) of the oral microbiota will suppress nitric oxide production via the nitrate-nitrite-nitric oxide pathway and negatively impact blood pressure. Conversely, there is preliminary evidence to suggest that proliferation of nitrate-reducing bacteria via the diet or targeted probiotics can augment nitric oxide production and improve markers of oral health. Despite this, it is yet to be established whether purposefully altering the oral microbiome can have a meaningful impact on exercise performance. Future research should determine whether alterations to the composition and metabolic activity of bacteria in the mouth influence the acute responses to exercise and the physiological adaptations to exercise training.}, }
@article {pmid35633673, year = {2022}, author = {Maestre-Carballa, L and Navarro-López, V and Martinez-Garcia, M}, title = {A Resistome Roadmap: From the Human Body to Pristine Environments.}, journal = {Frontiers in microbiology}, volume = {13}, number = {}, pages = {858831}, pmid = {35633673}, issn = {1664-302X}, abstract = {A comprehensive characterization of the human body resistome [sets of antibiotic resistance genes (ARGs)] is yet to be done and paramount for addressing the antibiotic microbial resistance threat. Here, we study the resistome of 771 samples from five major body parts (skin, nares, vagina, gut, and oral cavity) of healthy subjects from the Human Microbiome Project (HMP) and addressed the potential dispersion of ARGs in pristine environments. A total of 28,714 ARGs belonging to 235 different ARG types were found in the HMP proteome dataset (n = 9.1 × 10[7] proteins analyzed). Our study reveals a distinct resistome profile (ARG type and abundance) between body sites and high interindividual variability. Nares had the highest ARG load (≈5.4 genes/genome) followed by the oral cavity, whereas the gut showed one of the highest ARG richness (shared with nares) but the lowest abundance (≈1.3 genes/genome). The fluroquinolone resistance genes were the most abundant in the human body, followed by macrolide-lincosamide-streptogramin (MLS) or tetracycline. Most ARGs belonged to common bacterial commensals and multidrug resistance trait were predominant in the nares and vagina. Many ARGs detected here were considered as low risk for human health, whereas only a few of them, such as BlaZ, dfrA14, dfrA17, or tetM, were classified as high-risk ARG. Our data also provide hope, since the spread of common ARG from the human body to pristine environments (n = 271 samples; 77 Gb of sequencing data and 2.1 × 10[8] proteins analyzed) thus far remains very unlikely (only one case found in an autochthonous bacterium from a pristine environment). These findings broaden our understanding of ARG in the context of the human microbiome and the One-Health Initiative of WHO uniting human host-microbes and environments as a whole.}, }
@article {pmid35633665, year = {2022}, author = {El-Chami, C and Choudhury, R and Mohammedsaeed, W and McBain, AJ and Kainulainen, V and Lebeer, S and Satokari, R and O'Neill, CA}, title = {Multiple Proteins of Lacticaseibacillus rhamnosus GG Are Involved in the Protection of Keratinocytes From the Toxic Effects of Staphylococcus aureus.}, journal = {Frontiers in microbiology}, volume = {13}, number = {}, pages = {875542}, pmid = {35633665}, issn = {1664-302X}, abstract = {We have previously shown that lysates of Lacticaseibacillus rhamnosus GG confer protection to human keratinocytes against Staphylococcus aureus. L. rhamnosus GG inhibits the growth of S. aureus as well as competitively excludes and displaces the pathogen from keratinocytes. In this study, we have specifically investigated the anti-adhesive action. We have tested the hypothesis that this activity is due to quenching of S. aureus binding sites on keratinocytes by molecules within the Lacticaseibacillus lysate. Trypsinisation or heat treatment removed the protective effect of the lysate suggesting the involvement of proteins as effector molecules. Column separation of the lysate and analysis of discrete fractions in adhesion assays identified a fraction of moderate hydrophobicity that possessed all anti-adhesive functions. Immunoblotting demonstrated that this fraction contained the pilus protein, SpaC. Recombinant SpaC inhibited staphylococcal adhesion to keratinocytes in a dose-dependent manner and improved keratinocyte viability following challenge with viable S. aureus. However, SpaC did not confer the full anti-adhesive effects of the LGG lysate and excluded but did not displace S. aureus from keratinocytes. Further purification produced four protein-containing peaks (F1-F4). Of these, F4, which had the greatest column retention time, was the most efficacious in anti-staphylococcal adhesion and keratinocyte viability assays. Identification of proteins by mass spectrometry showed F4 to contain several known "moonlighting proteins"-i.e., with additional activities to the canonical function, including enolase, Triosephosphate isomerase (TPI), Glyceraldehyde 3 phosphate dehydrogenase (G3P) and Elongation factor TU (EF-Tu). Of these, only enolase and TPI inhibited S. aureus adhesion and protected keratinocytes viability in a dose-dependent manner. These data suggest that inhibition of staphylococcal binding by the L. rhamnosus GG lysate is mediated by SpaC and specific moonlight proteins.}, }
@article {pmid35632464, year = {2022}, author = {Brogna, C and Brogna, B and Bisaccia, DR and Lauritano, F and Marino, G and Montano, L and Cristoni, S and Prisco, M and Piscopo, M}, title = {Could SARS-CoV-2 Have Bacteriophage Behavior or Induce the Activity of Other Bacteriophages?.}, journal = {Vaccines}, volume = {10}, number = {5}, pages = {}, pmid = {35632464}, issn = {2076-393X}, abstract = {SARS-CoV-2 has become one of the most studied viruses of the last century. It was assumed that the only possible host for these types of viruses was mammalian eukaryotic cells. Our recent studies show that microorganisms in the human gastrointestinal tract affect the severity of COVID-19 and for the first time provide indications that the virus might replicate in gut bacteria. In order to further support these findings, in the present work, cultures of bacteria from the human microbiome and SARS-CoV-2 were analyzed by electron and fluorescence microscopy. The images presented in this article, in association with the nitrogen ([15]N) isotope-labeled culture medium experiment, suggest that SARS-CoV-2 could also infect bacteria in the gut microbiota, indicating that SARS-CoV-2 could act as a bacteriophage. Our results add new knowledge to the understanding of the mechanisms of SARS-CoV-2 infection and fill gaps in the study of the interactions between SARS-CoV-2 and non-mammalian cells. These findings could be useful in suggesting specific new pharmacological solutions to support the vaccination campaign.}, }
@article {pmid35631758, year = {2022}, author = {Harutyunyan, N and Kushugulova, A and Hovhannisyan, N and Pepoyan, A}, title = {One Health Probiotics as Biocontrol Agents: One Health Tomato Probiotics.}, journal = {Plants (Basel, Switzerland)}, volume = {11}, number = {10}, pages = {}, pmid = {35631758}, issn = {2223-7747}, support = {10-15/I-5; 21AG-4D065//State Committee of Science/ ; }, abstract = {Tomato (Lycopersicon esculentum) is one of the most popular and valuable vegetables in the world. The most common products of its industrial processing in the food industry are juice, tomato paste, various sauces, canned or sun-dried fruits and powdered products. Tomato fruits are susceptible to bacterial diseases, and bacterial contamination can be a risk factor for the safety of processed tomato products. Developments in bioinformatics allow researchers to discuss target probiotic strains from an existing large number of probiotic strains for any link in the soil-plant-animal-human chain. Based on the literature and knowledge on the "One Health" concept, this study relates to the suggestion of a new term for probiotics: "One Health probiotics", beneficial for the unity of people, animals, and the environment. Strains of Lactiplantibacillus plantarum, having an ability to ferment a broad spectrum of plant carbohydrates, probiotic effects in human, and animal health, as well as being found in dairy products, vegetables, sauerkraut, pickles, some cheeses, fermented sausages, fish products, and rhizospheric soil, might be suggested as one of the probable candidates for "One Health" probiotics (also, for "One Health-tomato" probiotics) for the utilization in agriculture, food processing, and healthcare.}, }
@article {pmid35631036, year = {2022}, author = {Pane, S and Putignani, L}, title = {Cryptosporidium: Still Open Scenarios.}, journal = {Pathogens (Basel, Switzerland)}, volume = {11}, number = {5}, pages = {}, pmid = {35631036}, issn = {2076-0817}, abstract = {Cryptosporidiosis is increasingly identified as a leading cause of childhood diarrhea and malnutrition in both low-income and high-income countries. The strong impact on public health in epidemic scenarios makes it increasingly essential to identify the sources of infection and understand the transmission routes in order to apply the right prevention or treatment protocols. The objective of this literature review was to present an overview of the current state of human cryptosporidiosis, reviewing risk factors, discussing advances in the drug treatment and epidemiology, and emphasizing the need to identify a government system for reporting diagnosed cases, hitherto undervalued.}, }
@article {pmid35629374, year = {2022}, author = {Puigbò, P and Leino, LI and Rainio, MJ and Saikkonen, K and Saloniemi, I and Helander, M}, title = {Does Glyphosate Affect the Human Microbiota?.}, journal = {Life (Basel, Switzerland)}, volume = {12}, number = {5}, pages = {}, pmid = {35629374}, issn = {2075-1729}, support = {311077//Academy of Finland/ ; N/A//Turku Collegium for Science, Medicine and Technology/ ; }, abstract = {Glyphosate is the world's most widely used agrochemical. Its use in agriculture and gardening has been proclaimed safe because humans and other animals do not have the target enzyme 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS). However, increasing numbers of studies have demonstrated risks to humans and animals because the shikimate metabolic pathway is present in many microbes. Here, we assess the potential effect of glyphosate on healthy human microbiota. Our results demonstrate that more than one-half of human microbiome are intrinsically sensitive to glyphosate. However, further empirical studies are needed to determine the effect of glyphosate on healthy human microbiota.}, }
@article {pmid35629064, year = {2022}, author = {Arjunan, P and Swaminathan, R}, title = {Do Oral Pathogens Inhabit the Eye and Play a Role in Ocular Diseases?.}, journal = {Journal of clinical medicine}, volume = {11}, number = {10}, pages = {}, pmid = {35629064}, issn = {2077-0383}, abstract = {Fascinatingly, the immune-privileged healthy eye has a small unique population of microbiota. The human microbiome project led to continuing interest in the ocular microbiome. Typically, ocular microflorae are commensals of low diversity that colonize the external and internal sites of the eye, without instigating any disorders. Ocular commensals modulate immunity and optimally regulate host defense against pathogenic invasion, both on the ocular surface and neuroretina. Yet, any alteration in this symbiotic relationship culminates in the perturbation of ocular homeostasis and shifts the equilibrium toward local or systemic inflammation and, in turn, impaired visual function. A compositional variation in the ocular microbiota is associated with surface disorders such as keratitis, blepharitis, and conjunctivitis. Nevertheless, innovative studies now implicate non-ocular microbial dysbiosis in glaucoma, age-related macular degeneration (AMD), uveitis, and diabetic retinopathy. Accordingly, prompt identification of the extra-ocular etiology and a methodical understanding of the mechanisms of invasion and host-microbial interaction is of paramount importance for preventative and therapeutic interventions for vision-threatening conditions. This review article aims to explore the current literature evidence to better comprehend the role of oral pathogens in the etiopathogenesis of ocular diseases, specifically AMD.}, }
@article {pmid35628138, year = {2022}, author = {Linkens, AMA and van Best, N and Niessen, PM and Wijckmans, NEG and de Goei, EEC and Scheijen, JLJM and van Dongen, MCJM and van Gool, CCJAW and de Vos, WM and Houben, AJHM and Stehouwer, CDA and Eussen, SJMP and Penders, J and Schalkwijk, CG}, title = {A 4-Week Diet Low or High in Advanced Glycation Endproducts Has Limited Impact on Gut Microbial Composition in Abdominally Obese Individuals: The deAGEing Trial.}, journal = {International journal of molecular sciences}, volume = {23}, number = {10}, pages = {}, pmid = {35628138}, issn = {1422-0067}, support = {95105002//Netherlands Organisation for Health Research and Development/ ; 2016.00.1865//Dutch Diabetes Research Foundation/ ; }, mesh = {Cross-Sectional Studies ; Diet ; Double-Blind Method ; *Gastrointestinal Microbiome ; *Glycation End Products, Advanced/administration &amp; dosage ; Humans ; *Obesity/diet therapy/microbiology ; RNA, Ribosomal, 16S/genetics ; }, abstract = {Dietary advanced glycation endproducts (AGEs), abundantly present in Westernized diets, are linked to negative health outcomes, but their impact on the gut microbiota has not yet been well investigated in humans. We investigated the effects of a 4-week isocaloric and macronutrient-matched diet low or high in AGEs on the gut microbial composition of 70 abdominally obese individuals in a double-blind parallel-design randomized controlled trial (NCT03866343). Additionally, we investigated the cross-sectional associations between the habitual intake of dietary dicarbonyls, reactive precursors to AGEs, and the gut microbial composition, as assessed by 16S rRNA amplicon-based sequencing. Despite a marked percentage difference in AGE intake, we observed no differences in microbial richness and the general community structure. Only the Anaerostipes spp. had a relative abundance >0.5% and showed differential abundance (0.5 versus 1.11%; p = 0.028, after low- or high-AGE diet, respectively). While the habitual intake of dicarbonyls was not associated with microbial richness or a general community structure, the intake of 3-deoxyglucosone was especially associated with an abundance of several genera. Thus, a 4-week diet low or high in AGEs has a limited impact on the gut microbial composition of abdominally obese humans, paralleling its previously observed limited biological consequences. The effects of dietary dicarbonyls on the gut microbiota composition deserve further investigation.}, }
@article {pmid35625219, year = {2022}, author = {Skurnik, M}, title = {Can Bacteriophages Replace Antibiotics?.}, journal = {Antibiotics (Basel, Switzerland)}, volume = {11}, number = {5}, pages = {}, pmid = {35625219}, issn = {2079-6382}, support = {2016//Jane and Aatos Erkko Foundation/ ; }, abstract = {Increasing antibiotic resistance numbers force both scientists and politicians to tackle the problem, and preferably without any delay. The application of bacteriophages as precision therapy to treat bacterial infections, phage therapy, has received increasing attention during the last two decades. While it looks like phage therapy is here to stay, there is still a lot to do. Medicine regulatory authorities are working to deliver clear instructions to carry out phage therapy. Physicians need to get more practical experience on treatments with phages. In this opinion article I try to place phage therapy in the context of the health care system and state that the use phages for precision treatments will require a seamless chain of events from the patient to the phage therapy laboratory to allow for the immediate application of phages therapeutically. It is not likely that phages will replace antibiotics, however, they will be valuable in the treatment of infections caused by multidrug resistant bacteria. Antibiotics will nevertheless remain the main treatment for a majority of infections.}, }
@article {pmid35624309, year = {2022}, author = {Gavin, DP and Reen, FJ and Rocha-Martin, J and Abreu-Castilla, I and Woods, DF and Foley, AM and Sánchez-Murcia, PA and Schwarz, M and O'Neill, P and Maguire, AR and O'Gara, F}, title = {Author Correction: Genome mining and characterisation of a novel transaminase with remote stereoselectivity.}, journal = {Scientific reports}, volume = {12}, number = {1}, pages = {8947}, doi = {10.1038/s41598-022-12801-5}, pmid = {35624309}, issn = {2045-2322}, }
@article {pmid35620320, year = {2022}, author = {Li, X and Wang, L and Ma, S and Lin, S and Wang, C and Wang, H}, title = {Combination of Oxalobacter Formigenes and Veillonella Parvula in Gastrointestinal Microbiota Related to Bile-Acid Metabolism as a Biomarker for Hypertensive Nephropathy.}, journal = {International journal of hypertension}, volume = {2022}, number = {}, pages = {5999530}, pmid = {35620320}, issn = {2090-0384}, abstract = {The human microbiome is a mixed group of microorganisms, which individually consists of 10-100 trillion symbiotic microbial cells. The relationship between gastrointestinal microbiota and blood pressure has been verified and the intestinal microbiota of chronic kidney disease (CKD) patients in the distribution of bacterial species is different from the flora of people with no CKD. The purpose of this research is to study the different intestinal microbiota of hypertensive patients with and without nephropathy and to find possible biomarkers of hypertensive nephropathy (H-CKD). The subjects of this research were divided into three groups, healthy control group, hypertension group, and hypertensive nephropathy group. Sequencing, bioinformatics, and statistical analysis were performed on the 16S rRNA gene of the subjects' stool samples. This research study showed the differences of intestinal flora as biomarkers in hypertension patients with and without nephropathy; it investigated the relationship of the differences in the intestinal microbiota with bile-acid metabolism; it also explored bile-acid metabolism mechanism of intestinal microbiota differences in hypertension with or without nephropathy. In summary, the difference in the combination of O. formigenes and V. parvula in the gastrointestinal microbiota is related to bile-acid metabolism in hypertensive patients and can be one of the factors causing CKD. It is the first time to report such a biomarker or pathogenic factor of H-CKD in the world.}, }
@article {pmid35616767, year = {2022}, author = {Hasan, R and Bose, S and Roy, R and Paul, D and Rawat, S and Nilwe, P and Chauhan, NK and Choudhury, S}, title = {Tumor tissue-specific bacterial biomarker panel for colorectal cancer: Bacteroides massiliensis, Alistipes species, Alistipes onderdonkii, Bifidobacterium pseudocatenulatum, Corynebacterium appendicis.}, journal = {Archives of microbiology}, volume = {204}, number = {6}, pages = {348}, pmid = {35616767}, issn = {1432-072X}, support = {4.9.36-011//Sir Ganga Ram Hospital, Research and Development programme/ ; }, mesh = {Bacteria/genetics ; Bacteroides ; Bacteroidetes ; *Bifidobacterium pseudocatenulatum/genetics ; Biomarkers, Tumor/genetics ; *Colorectal Neoplasms/diagnosis/microbiology ; Corynebacterium ; *Gastrointestinal Microbiome/genetics ; Humans ; RNA, Ribosomal, 16S/genetics ; }, abstract = {Human microbiome studies have shown diversity to exist among different ethnic populations. However, studies pertaining to the microbial composition of CRC among the Indian population have not been well explored. We aimed to decipher the microbial signature in tumor tissues from North Indian CRC patients. Next-generation sequencing of tumor and adjacent tissue-derived bacterial 16S rRNA V3-V4 hypervariable regions was performed to investigate the abundance of specific microbes. The expression profile analysis deciphered a decreased diversity among the tumor-associated microbial communities. At the phyla level, Proteobacteria was differentially expressed in CRC tissues than adjacent normal. Further, DeSeq2 normalization identified 4 out of 79 distinct species (p < 0.005) only in CRC, Bacteroides massiliensis, Alistipes onderdonkii, Bifidobacterium pseudocatenulatum, and Corynebacterium appendicis. Thus, the findings suggest that microbial signatures can be used as putative biomarkers in diagnosis, prognosis and treatment management of CRC.}, }
@article {pmid35611465, year = {2022}, author = {Gulliver, EL and Young, RB and Chonwerawong, M and D'Adamo, GL and Thomason, T and Widdop, JT and Rutten, EL and Rossetto Marcelino, V and Bryant, RV and Costello, SP and O'Brien, CL and Hold, GL and Giles, EM and Forster, SC}, title = {Review article: the future of microbiome-based therapeutics.}, journal = {Alimentary pharmacology &amp; therapeutics}, volume = {56}, number = {2}, pages = {192-208}, pmid = {35611465}, issn = {1365-2036}, mesh = {Fecal Microbiota Transplantation ; Humans ; *Microbiota ; Prebiotics ; *Probiotics/therapeutic use ; *Synbiotics ; }, abstract = {BACKGROUND: From consumption of fermented foods and probiotics to emerging applications of faecal microbiota transplantation, the health benefit of manipulating the human microbiota has been exploited for millennia. Despite this history, recent technological advances are unlocking the capacity for targeted microbial manipulation as a novel therapeutic.<br><br>AIM: This review summarises the current developments in microbiome-based medicines and provides insight into the next steps required for therapeutic development.<br><br>METHODS: Here we review current and emerging approaches and assess the capabilities and weaknesses of these technologies to provide safe and effective clinical interventions. Key literature was identified through Pubmed searches with the following key words, 'microbiome', 'microbiome biomarkers', 'probiotics', 'prebiotics', 'synbiotics', 'faecal microbiota transplant', 'live biotherapeutics', 'microbiome mimetics' and 'postbiotics'.<br><br>RESULTS: Improved understanding of the human microbiome and recent technological advances provide an opportunity to develop a new generation of therapies. These therapies will range from dietary interventions, prebiotic supplementations, single probiotic bacterial strains, human donor-derived faecal microbiota transplants, rationally selected combinations of bacterial strains as live biotherapeutics, and the beneficial products or effects produced by bacterial strains, termed microbiome mimetics.<br><br>CONCLUSIONS: Although methods to identify and refine these therapeutics are continually advancing, the rapid emergence of these new approaches necessitates accepted technological and ethical frameworks for measurement, testing, laboratory practices and clinical translation.}, }
@article {pmid35608350, year = {2022}, author = {Tong, X and Yu, X and Du, Y and Su, F and Liu, Y and Li, H and Liu, Y and Mu, K and Liu, Q and Li, H and Zhu, J and Xu, H and Xiao, F and Li, Y}, title = {Peripheral Blood Microbiome Analysis via Noninvasive Prenatal Testing Reveals the Complexity of Circulating Microbial Cell-Free DNA.}, journal = {Microbiology spectrum}, volume = {10}, number = {3}, pages = {e0041422}, pmid = {35608350}, issn = {2165-0497}, mesh = {*Cell-Free Nucleic Acids/genetics ; *Epstein-Barr Virus Infections ; Female ; Herpesvirus 4, Human ; Humans ; *Microbiota/genetics ; *Noninvasive Prenatal Testing ; Pregnancy ; Retrospective Studies ; }, abstract = {While circulating cell-free DNA (cfDNA) is becoming a powerful marker for noninvasive identification of infectious pathogens in liquid biopsy specimens, a microbial cfDNA baseline in healthy individuals is urgently needed for the proper interpretation of microbial cfDNA sequencing results in clinical metagenomics. Because noninvasive prenatal testing (NIPT) shares many similarities with the sequencing protocol of metagenomics, we utilized the standard low-pass whole-genome-sequencing-based NIPT to establish a microbial cfDNA baseline in healthy people. Sequencing data from a total of 107,763 peripheral blood samples of healthy pregnant women undergoing NIPT screening were retrospectively collected and reanalyzed for microbiome DNA screening. It was found that more than 95% of exogenous cfDNA was from bacteria, 3% from eukaryotes, and 0.4% from viruses, indicating the gut/environment origins of many microorganisms. Overall and regional abundance patterns were well illustrated, with huge regional diversity and complexity, and unique interspecies and symbiotic relationships were observed for TORCH organisms (Toxoplasma gondii, others [Treponema pallidum {causing syphilis}, hepatitis B virus {HBV}, and human parvovirus B19 {HPV-B19}], rubella virus, cytomegalovirus [CMV], and herpes simplex virus [HSV]) and another common virus, Epstein-Barr virus (EBV). To sum up, our study revealed the complexity of the baseline circulating microbial cfDNA and showed that microbial cfDNA sequencing results need to be interpreted in a more comprehensive manner. IMPORTANCE While circulating cell-free DNA (cfDNA) has been becoming a powerful marker for noninvasive identification of infectious pathogens in liquid biopsy specimens, a baseline for microbial cfDNA in healthy individuals is urgently needed for the proper interpretation of microbial cfDNA sequencing results in clinical metagenomics. Standard low-pass whole-genome-sequencing-based NIPT shares many similarities with the sequencing protocol for metagenomics and could provide a microbial cfDNA baseline in healthy people; thus, a reference cfDNA data set of the human microbiome was established with sequencing data from a total of 107,763 peripheral blood samples of healthy pregnant women undergoing NIPT screening. Our study revealed the complexity of circulating microbial cfDNA and indicated that microbial cfDNA sequencing results need to be interpreted in a more comprehensive manner, especially with regard to geographic patterns and coexistence networks.}, }
@article {pmid35603752, year = {2023}, author = {Nabizadeh, E and Sadeghi, J and Ahangarzadeh Rezaee, M and Hasani, A and Samadi Kafil, H and Ghotaslou, A and Kadkhoda, H and Ghotaslou, R}, title = {Interaction Between Altered Gut Microbiota and Sepsis: A Hypothesis or an Authentic Fact?.}, journal = {Journal of intensive care medicine}, volume = {38}, number = {1}, pages = {121-131}, doi = {10.1177/08850666221102796}, pmid = {35603752}, issn = {1525-1489}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; Dysbiosis ; *Microbiota ; *Sepsis ; Immune System ; }, abstract = {Sepsis, as an important public health concern, is one of the leading causes of death in hospitals around the world, accounting for 25% of all deaths. Nowadays, several factors contribute to the development of sepsis. The role of the gut microbiota and the response state of the aberrant immune system is dominant. The effect of the human microbiome on health is undeniable, and gut microbiota is even considered a body organ. It is now clear that the alteration in the normal balance of the microbiota (dysbiosis) is associated with a change in the status of immune system responses. Owing to the strong association between the gut microbiota and its metabolites particularly short-chain fatty acids with many illnesses, the gut microbiota has a unique position in the research of microbiologists and even clinicians. This review aimed to analyze studies' results on the association between microbiota and sepsis, with a substantial understanding of their relationship. As a result, an extensive and comprehensive search was conducted on this issue in existing databases.}, }
@article {pmid35601739, year = {2022}, author = {Issilbayeva, A and Ainabekova, B and Zhetkenev, S and Meiramova, A and Akhmetova, Z and Karina, K and Kozhakhmetov, S and Nurgaziyev, M and Chulenbayeva, L and Poddighe, D and Kunz, J and Kushugulova, A}, title = {Association Study of Anticitrullinated Peptide Antibody Status with Clinical Manifestations and SNPs in Patients Affected with Rheumatoid Arthritis: A Pilot Study.}, journal = {Disease markers}, volume = {2022}, number = {}, pages = {2744762}, pmid = {35601739}, issn = {1875-8630}, mesh = {*Arthritis, Rheumatoid ; Autoantibodies ; Female ; Genome-Wide Association Study ; Humans ; Peptides ; Pilot Projects ; *Polymorphism, Single Nucleotide ; }, abstract = {INTRODUCTION: Rheumatoid arthritis (RA) is an autoimmune disease of unknown etiology that leads to disability due to articular and extra-articular damage. RA prevalence is variable. The disease is most common among females with a 3 : 1 ratio. The interaction of environmental and host factors contributes to RA development. Currently, the genome-wide association studies (GWAS) give the opportunity to uncover the RA genetic background. Anticitrullinated peptide antibody (ACPA) is a highly specific RA antibody, associated with poor prognosis and severe course of RA, and regulated by numerous genes. Our study is aimed at investigating whether there are any clinical and genetic aspects correlate with ACPA presence in Kazakhstani patients with RA. Indeed, the available studies on this subject are focused on Caucasian and East Asian populations (mainly Japanese and Chinese), and there are scarce data from Central Asia.<br><br>METHODS: Our study included 70 RA patients. Patients' blood samples were collected and genotyped for 14 SNPs by real-time polymerase chain reaction (RT-PCR). General examination, anamnestic, and clinical and laboratory data collection were carried out. Statistical analysis was performed using R statistics. Results and Conclusion. Our study revealed a significant association of ACPA positivity with Fc receptor-like 3 (FCRL3) and ACPA negativity with signal transducer and activator of transcription 4 (STAT4) genes, but not with T cell activation Rho GTPase activating protein (TAGAP). In addition, ACPA positivity was associated with radiographic progression, rheumatoid factor (RF), erythrocyte sedimentation rate (ESR), age of RA onset, the patient global assessment, body mass index (BMI), and Gamma globulin.<br><br>CONCLUSION: Remained 11 earlier identified significantly associated in Caucasian and Asian population SNPs were not replicated in our cohort. Further studies on larger cohorts are needed to confirm our findings with higher confidence levels and stronger statistical power.}, }
@article {pmid35599315, year = {2022}, author = {Jian, C and Silvestre, MP and Middleton, D and Korpela, K and Jalo, E and Broderick, D and de Vos, WM and Fogelholm, M and Taylor, MW and Raben, A and Poppitt, S and Salonen, A}, title = {Gut microbiota predicts body fat change following a low-energy diet: a PREVIEW intervention study.}, journal = {Genome medicine}, volume = {14}, number = {1}, pages = {54}, pmid = {35599315}, issn = {1756-994X}, mesh = {Adipose Tissue/metabolism ; Adult ; Butyrates/pharmacology ; Diet ; Feces/microbiology ; *Gastrointestinal Microbiome ; Humans ; Overweight/metabolism ; *Prediabetic State ; RNA, Ribosomal, 16S/genetics ; Weight Loss ; }, abstract = {BACKGROUND: Low-energy diets (LEDs) comprise commercially formulated food products that provide between 800 and 1200 kcal/day (3.3-5 MJ/day) to aid body weight loss. Recent small-scale studies suggest that LEDs are associated with marked changes in the gut microbiota that may modify the effect of the LED on host metabolism and weight loss. We investigated how the gut microbiota changed during 8 weeks of total meal replacement LED and determined their associations with host response in a sub-analysis of 211 overweight adults with pre-diabetes participating in the large multicentre PREVIEW (PREVention of diabetes through lifestyle intervention and population studies In Europe and around the World) clinical trial.<br><br>METHODS: Microbial community composition was analysed by Illumina sequencing of the hypervariable V3-V4 regions of the 16S ribosomal RNA (rRNA) gene. Butyrate production capacity was estimated by qPCR targeting the butyryl-CoA:acetate CoA-transferase gene. Bioinformatics and statistical analyses, such as comparison of alpha and beta diversity measures, correlative and differential abundances analysis, were undertaken on the 16S rRNA gene sequences of 211 paired (pre- and post-LED) samples as well as their integration with the clinical, biomedical and dietary datasets for predictive modelling.<br><br>RESULTS: The overall composition of the gut microbiota changed markedly and consistently from pre- to post-LED (P = 0.001), along with increased richness and diversity (both P < 0.001). Following the intervention, the relative abundance of several genera previously associated with metabolic improvements (e.g., Akkermansia and Christensenellaceae R-7 group) was significantly increased (P < 0.001), while flagellated Pseudobutyrivibrio, acetogenic Blautia and Bifidobacterium spp. were decreased (all P < 0.001). Butyrate production capacity was reduced (P < 0.001). The changes in microbiota composition and predicted functions were significantly associated with body weight loss (P < 0.05). Baseline gut microbiota features were able to explain ~25% of variation in total body fat change (post-pre-LED).<br><br>CONCLUSIONS: The gut microbiota and individual taxa were significantly influenced by the LED intervention and correlated with changes in total body fat and body weight in individuals with overweight and pre-diabetes. Despite inter-individual variation, the baseline gut microbiota was a strong predictor of total body fat change during the energy restriction period.<br><br>TRIAL REGISTRATION: The PREVIEW trial was prospectively registered at ClinicalTrials.gov (NCT01777893) on January 29, 2013.}, }
@article {pmid35593892, year = {2022}, author = {Hansen, ME and Yasmin, SO and Wolfrum, S and Carreira, EM}, title = {Total Synthesis of Mutanobactins A, B from the Human Microbiome: Macrocyclization and Thiazepanone Assembly in a Single Step.}, journal = {Angewandte Chemie (International ed. in English)}, volume = {61}, number = {28}, pages = {e202203051}, pmid = {35593892}, issn = {1521-3773}, mesh = {Cyclization ; Humans ; Lipopeptides/chemistry ; *Microbiota ; *Peptides, Cyclic/chemistry ; Solid-Phase Synthesis Techniques ; }, abstract = {We report the first total syntheses of tricyclic mutanobactins A and B, lipopeptides incorporating a thiazepanone, isolated from Streptococcus mutans, a member of the human oral microbiome. A rapid, solid-phase peptide synthesis (SPPS) based route delivers these natural products from a cascade of cyclization reactions. This versatile process was also employed in a streamlined synthesis of mutanobactin D. Additionally, we provide an independent synthesis of a truncated mutanobactin A analog, utilizing a novel thiazepanone amino acid building block.}, }
@article {pmid35590169, year = {2021}, author = {Song, SJ and Wang, J and Martino, C and Jiang, L and Thompson, WK and Shenhav, L and McDonald, D and Marotz, C and Harris, PR and Hernandez, CD and Henderson, N and Ackley, E and Nardella, D and Gillihan, C and Montacuti, V and Schweizer, W and Jay, M and Combellick, J and Sun, H and Garcia-Mantrana, I and Gil Raga, F and Collado, MC and Rivera-Viñas, JI and Campos-Rivera, M and Ruiz-Calderon, JF and Knight, R and Dominguez-Bello, MG}, title = {Naturalization of the microbiota developmental trajectory of Cesarean-born neonates after vaginal seeding.}, journal = {Med (New York, N.Y.)}, volume = {2}, number = {8}, pages = {951-964.e5}, pmid = {35590169}, issn = {2666-6340}, support = {DP1 AT010885/AT/NCCIH NIH HHS/United States ; P30 DK120515/DK/NIDDK NIH HHS/United States ; }, mesh = {*Cesarean Section/adverse effects ; Citizenship ; Female ; Humans ; Infant ; Infant, Newborn ; Longitudinal Studies ; *Microbiota/genetics ; Pregnancy ; RNA, Ribosomal, 16S/genetics ; }, abstract = {BACKGROUND: Early microbiota perturbations are associated with disorders that involve immunological underpinnings. Cesarean section (CS)-born babies show altered microbiota development in relation to babies born vaginally. Here we present the first statistically powered longitudinal study to determine the effect of restoring exposure to maternal vaginal fluids after CS birth.<br><br>METHODS: Using 16S rRNA gene sequencing, we followed the microbial trajectories of multiple body sites in 177 babies over the first year of life; 98 were born vaginally, and 79 were born by CS, of whom 30 were swabbed with a maternal vaginal gauze right after birth.<br><br>FINDINGS: Compositional tensor factorization analysis confirmed that microbiota trajectories of exposed CS-born babies aligned more closely with that of vaginally born babies. Interestingly, the majority of amplicon sequence variants from maternal vaginal microbiomes on the day of birth were shared with other maternal sites, in contrast to non-pregnant women from the Human Microbiome Project (HMP) study.<br><br>CONCLUSIONS: The results of this observational study prompt urgent randomized clinical trials to test whether microbial restoration reduces the increased disease risk associated with CS birth and the underlying mechanisms. It also provides evidence of the pluripotential nature of maternal vaginal fluids to provide pioneer bacterial colonizers for the newborn body sites. This is the first study showing long-term naturalization of the microbiota of CS-born infants by restoring microbial exposure at birth.<br><br>FUNDING: C&amp;D, Emch Fund, CIFAR, Chilean CONICYT and SOCHIPE, Norwegian Institute of Public Health, Emerald Foundation, NIH, National Institute of Justice, Janssen.}, }
@article {pmid35589762, year = {2022}, author = {Szóstak, N and Szymanek, A and Havránek, J and Tomela, K and Rakoczy, M and Samelak-Czajka, A and Schmidt, M and Figlerowicz, M and Majta, J and Milanowska-Zabel, K and Handschuh, L and Philips, A}, title = {The standardisation of the approach to metagenomic human gut analysis: from sample collection to microbiome profiling.}, journal = {Scientific reports}, volume = {12}, number = {1}, pages = {8470}, pmid = {35589762}, issn = {2045-2322}, mesh = {DNA ; Humans ; Metagenome ; *Metagenomics/methods ; *Microbiota/genetics ; RNA, Ribosomal, 16S/genetics ; Reproducibility of Results ; }, abstract = {In recent years, the number of metagenomic studies increased significantly. Wide range of factors, including the tremendous community complexity and variability, is contributing to the challenge in reliable microbiome community profiling. Many approaches have been proposed to overcome these problems making hardly possible to compare results of different studies. The significant differences between procedures used in metagenomic research are reflected in a variation of the obtained results. This calls for the need for standardisation of the procedure, to reduce the confounding factors originating from DNA isolation, sequencing and bioinformatics analyses in order to ensure that the differences in microbiome composition are of a true biological origin. Although the best practices for metagenomics studies have been the topic of several publications and the main aim of the International Human Microbiome Standard (IHMS) project, standardisation of the procedure for generating and analysing metagenomic data is still far from being achieved. To highlight the difficulties in the standardisation of metagenomics methods, we thoroughly examined each step of the analysis of the human gut microbiome. We tested the DNA isolation procedure, preparation of NGS libraries for next-generation sequencing, and bioinformatics analysis, aimed at identifying microbial taxa. We showed that the homogenisation time is the leading factor impacting sample diversity, with the recommendation for a shorter homogenisation time (10 min). Ten minutes of homogenisation allows for better reflection of the bacteria gram-positive/gram-negative ratio, and the obtained results are the least heterogenous in terms of beta-diversity of samples microbial composition. Besides increasing the homogenisation time, we observed further potential impact of the library preparation kit on the gut microbiome profiling. Moreover, our analysis revealed that the choice of the library preparation kit influences the reproducibility of the results, which is an important factor that has to be taken into account in every experiment. In this study, a tagmentation-based kit allowed for obtaining the most reproducible results. We also considered the choice of the computational tool for determining the composition of intestinal microbiota, with Kraken2/Bracken pipeline outperforming MetaPhlAn2 in our in silico experiments. The design of an experiment and a detailed establishment of an experimental protocol may have a serious impact on determining the taxonomic profile of the intestinal microbiome community. Results of our experiment can be helpful for a wide range of studies that aim to better understand the role of the gut microbiome, as well as for clinical purposes.}, }
@article {pmid35579554, year = {2022}, author = {Sim, M and Lee, J and Wy, S and Park, N and Lee, D and Kwon, D and Kim, J}, title = {Generation and application of pseudo-long reads for metagenome assembly.}, journal = {GigaScience}, volume = {11}, number = {}, pages = {}, pmid = {35579554}, issn = {2047-217X}, mesh = {High-Throughput Nucleotide Sequencing/methods ; Humans ; *Metagenome ; Metagenomics/methods ; *Microbiota/genetics ; Sequence Analysis, DNA/methods ; }, abstract = {BACKGROUND: Metagenomic assembly using high-throughput sequencing data is a powerful method to construct microbial genomes in environmental samples without cultivation. However, metagenomic assembly, especially when only short reads are available, is a complex and challenging task because mixed genomes of multiple microorganisms constitute the metagenome. Although long read sequencing technologies have been developed and have begun to be used for metagenomic assembly, many metagenomic studies have been performed based on short reads because the generation of long reads requires higher sequencing cost than short reads.<br><br>RESULTS: In this study, we present a new method called PLR-GEN. It creates pseudo-long reads from metagenomic short reads based on given reference genome sequences by considering small sequence variations existing in individual genomes of the same or different species. When applied to a mock community data set in the Human Microbiome Project, PLR-GEN dramatically extended short reads in length of 101&#xa0;bp to pseudo-long reads with N50 of 33&#xa0;Kbp and 0.4% error rate. The use of these pseudo-long reads generated by PLR-GEN resulted in an obvious improvement of metagenomic assembly in terms of the number of sequences, assembly contiguity, and prediction of species and genes.<br><br>CONCLUSIONS: PLR-GEN can be used to generate artificial long read sequences without spending extra sequencing cost, thus aiding various studies using metagenomes.}, }
@article {pmid35579384, year = {2022}, author = {Furber, MJW and Young, GR and Holt, GS and Pyle, S and Davison, G and Roberts, MG and Roberts, JD and Howatson, G and Smith, DL}, title = {Gut Microbial Stability is Associated with Greater Endurance Performance in Athletes Undertaking Dietary Periodization.}, journal = {mSystems}, volume = {7}, number = {3}, pages = {e0012922}, pmid = {35579384}, issn = {2379-5077}, mesh = {Humans ; *Gastrointestinal Microbiome ; Physical Endurance ; Diet ; Athletes ; Dietary Carbohydrates ; }, abstract = {Dietary manipulation with high-protein or high-carbohydrate content are frequently employed during elite athletic training, aiming to enhance athletic performance. Such interventions are likely to impact upon gut microbial content. This study explored the impact of acute high-protein or high-carbohydrate diets on measured endurance performance and associated gut microbial community changes. In a cohort of well-matched, highly trained endurance runners, we measured performance outcomes, as well as gut bacterial, viral (FVP), and bacteriophage (IV) communities in a double-blind, repeated-measures design randomized control trial (RCT) to explore the impact of dietary intervention with either high-protein or high-carbohydrate content. High-dietary carbohydrate improved time-trial performance by +6.5% (P < 0.03) and was associated with expansion of Ruminococcus and Collinsella bacterial spp. Conversely, high dietary protein led to a reduction in performance by -23.3% (P = 0.001). This impact was accompanied by significantly reduced diversity (IV: P = 0.04) and altered composition (IV and FVP: P = 0.02) of the gut phageome as well as enrichment of both free and inducible Sk1virus and Leuconostoc bacterial populations. Greatest performance during dietary modification was observed in participants with less substantial shifts in community composition. Gut microbial stability during acute dietary periodization was associated with greater athletic performance in this highly trained, well-matched cohort. Athletes, and those supporting them, should be mindful of the potential consequences of dietary manipulation on gut flora and implications for performance, and periodize appropriately. IMPORTANCE Dietary periodization is employed to improve endurance exercise performance but may impact on gut microbial communities. Bacteriophage are implicated in bacterial cell homeostasis and have been identified as biomarkers of disequilibrium in the gut ecosystem possibly brought about through dietary periodization. We find high-carbohydrate and high-protein diets to have opposing impacts on endurance performance in highly trained athlete populations. Reduced performance is linked with disturbance of microbial stasis in the gut. We demonstrate bacteriophage communities are the most sensitive component of the gut microbiota to increased gut stress following dietary manipulation. Athletes undertaking dietary periodization should be aware of potential negative impacts of drastic changes to dietary composition on gut microbial stasis and, in turn, endurance performance.}, }
@article {pmid35577973, year = {2022}, author = {Mangola, SM and Lund, JR and Schnorr, SL and Crittenden, AN}, title = {Ethical microbiome research with Indigenous communities.}, journal = {Nature microbiology}, volume = {7}, number = {6}, pages = {749-756}, pmid = {35577973}, issn = {2058-5276}, support = {RM1 HG009042/HG/NHGRI NIH HHS/United States ; }, mesh = {Humans ; *Microbiota ; }, abstract = {Human-microbiome interactions have been associated with evolutionary, cultural and environmental processes. With clinical applications of microbiome research now feasible, it is crucial that the science conducted, particularly among Indigenous communities, adheres to principles of inclusion. This necessitates a transdisciplinary dialogue to decide how biological samples are collected and who benefits from the research and any derived products. As a group of scholars working at the interface of biological and social science, we offer a candid discussion of the lessons learned from our own research and introduce one approach to carry out ethical microbiome research with Indigenous communities.}, }
@article {pmid35577391, year = {2022}, author = {Kantele, A and Paajanen, J and Turunen, S and Pakkanen, SH and Patjas, A and Itkonen, L and Heiskanen, E and Lappalainen, M and Desquilbet, L and Vapalahti, O and Hielm-Björkman, A}, title = {Scent dogs in detection of COVID-19: triple-blinded randomised trial and operational real-life screening in airport setting.}, journal = {BMJ global health}, volume = {7}, number = {5}, pages = {}, pmid = {35577391}, issn = {2059-7908}, mesh = {Airports ; Animals ; *COVID-19/diagnosis ; Dogs ; Humans ; Odorants ; *SARS-CoV-2 ; }, abstract = {OBJECTIVE: To estimate scent dogs' diagnostic accuracy in identification of people infected with SARS-CoV-2 in comparison with reverse transcriptase polymerase chain reaction (RT-PCR). We conducted a randomised triple-blinded validation trial, and a real-life study at the Helsinki-Vantaa International Airport, Finland.<br><br>METHODS: Four dogs were trained to detect COVID-19 using skin swabs from individuals tested for SARS-CoV-2 by RT-PCR. Our controlled triple-blinded validation study comprised four identical sets of 420 parallel samples (from 114 individuals tested positive and 306 negative by RT-PCR), randomly presented to each dog over seven trial sessions. In a real-life setting the dogs screened skin swabs from 303 incoming passengers all concomitantly examined by nasal swab SARS-CoV-2 RT-PCR. Our main outcomes were variables of diagnostic accuracy (sensitivity, specificity, positive predictive value, negative predictive value) for scent dog identification in comparison with RT-PCR.<br><br>RESULTS: Our validation experiments had an overall accuracy of 92% (95% CI 90% to 93%), a sensitivity of 92% (95% CI 89% to 94%) and a specificity of 91% (95% CI 89% to 93%) compared with RT-PCR. For our dogs, trained using the wild-type virus, performance was less accurate for the alpha variant (89% for confirmed wild-type vs 36% for alpha variant, OR 14.0, 95%&#x2009;CI 4.5 to 43.4). In the real-life setting, scent detection and RT-PCR matched 98.7% of the negative swabs. Scant airport prevalence (0.47%) did not allow sensitivity testing; our only SARS-CoV-2 positive swab was not identified (alpha variant). However, ad hoc analysis including predefined positive spike samples showed a total accuracy of 98% (95% CI 97% to 99%).<br><br>CONCLUSIONS: This large randomised controlled triple-blinded validation study with a precalculated sample size conducted at an international airport showed that trained scent dogs screen airport passenger samples with high accuracy. One of our findings highlights the importance of continuous retraining as new variants emerge. Using scent dogs may present a valuable approach for high-throughput, rapid screening of large numbers of people.}, }
@article {pmid35572708, year = {2022}, author = {Vindenes, HK and Lin, H and Shigdel, R and Ringel-Kulka, T and Real, FG and Svanes, C and Peddada, SD and Bertelsen, RJ}, title = {Exposure to Antibacterial Chemicals Is Associated With Altered Composition of Oral Microbiome.}, journal = {Frontiers in microbiology}, volume = {13}, number = {}, pages = {790496}, pmid = {35572708}, issn = {1664-302X}, abstract = {Antimicrobial chemicals are used as preservatives in cosmetics, pharmaceuticals, and food to prevent the growth of bacteria and fungi in the products. Unintentional exposure in humans to such chemicals is well documented, but whether they also interfere with human oral microbiome composition is largely unexplored. In this study, we explored whether the oral bacterial composition is affected by exposure to antibacterial and environmental chemicals. Gingival fluid, urine, and interview data were collected from 477 adults (18-47 years) from the RHINESSA study in Bergen, Norway. Urine biomarkers of triclosan, triclocarban, parabens, benzophenone-3, bisphenols, and 2,4- and 2,5-dichlorophenols (DCPs) were quantified (by mass spectrometry). Microbiome analysis was based on 16S amplicon sequencing. Diversity and differential abundance analyses were performed to identify how microbial communities may change when comparing groups of different chemical exposure. We identified that high urine levels (>75th percentile) of propyl parabens were associated with a lower abundance of bacteria genera TM7 [G-3], Helicobacter, Megasphaera, Mitsuokella, Tannerella, Propionibacteriaceae [G-2], and Dermabacter, as compared with low propylparaben levels (<25[th] percentile). High exposure to ethylparaben was associated with a higher abundance of Paracoccus. High urine levels of bisphenol A were associated with a lower abundance of Streptococcus and exposure to another environmental chemical, 2,4-DCP, was associated with a lower abundance of Treponema, Fretibacterium, and Bacteroidales [G-2]. High exposure to antibacterial and environmental chemicals was associated with an altered composition of gingiva bacteria; mostly commensal bacteria in the oral cavity. Our results highlight a need for a better understanding of how antimicrobial chemical exposure influences the human microbiome.}, }
@article {pmid35558108, year = {2022}, author = {Rosas-Plaza, S and Hernández-Terán, A and Navarro-Díaz, M and Escalante, AE and Morales-Espinosa, R and Cerritos, R}, title = {Human Gut Microbiome Across Different Lifestyles: From Hunter-Gatherers to Urban Populations.}, journal = {Frontiers in microbiology}, volume = {13}, number = {}, pages = {843170}, pmid = {35558108}, issn = {1664-302X}, abstract = {Human lifestyle and its relationship with the human microbiome has been a line of research widely studied. This is because, throughout human history, civilizations have experienced different environments and lifestyles that could have promoted changes in the human microbiome. The comparison between industrialized and non-industrialized human populations in several studies has allowed to observe variation in the microbiome structure due to the population lifestyle. Nevertheless, the lifestyle of human populations is a gradient where several subcategories can be described. Yet, it is not known how these different lifestyles of human populations affect the microbiome structure on a large scale. Therefore, the main goal of this work was the collection and comparison of 16S data from the gut microbiome of populations that have different lifestyles around the world. With the data obtained from 14 studies, it was possible to compare the gut microbiome of 568 individuals that represent populations of hunter-gatherers, agricultural, agropastoral, pastoral, and urban populations. Results showed that industrialized populations present less diversity than those from non-industrialized populations, as has been described before. However, by separating traditional populations into different categories, we were able to observe patterns that cannot be appreciated by encompassing the different traditional lifestyles in a single category. In this sense, we could confirm that different lifestyles exhibit distinct alpha and beta diversity. In particular, the gut microbiome of pastoral and agropastoral populations seems to be more similar to those of urban populations according to beta diversity analysis. Beyond that, beta diversity analyses revealed that bacterial composition reflects the different lifestyles, representing a transition from hunters-gatherers to industrialized populations. Also, we found that certain groups such as Bacteoidaceae, Lanchospiraceae, and Rickenellaceae have been favored in the transition to modern societies, being differentially abundant in urban populations. Thus, we could hypothesize that due to adaptive/ecological processes; multifunctional bacterial groups (e.g., Bacteroidaceae) could be replacing some functions lost in the transition to modern lifestyle.}, }
@article {pmid35549618, year = {2022}, author = {Chen, L and Zheng, T and Yang, Y and Chaudhary, PP and Teh, JPY and Cheon, BK and Moses, D and Schuster, SC and Schlundt, J and Li, J and Conway, PL}, title = {Integrative multiomics analysis reveals host-microbe-metabolite interplays associated with the aging process in Singaporeans.}, journal = {Gut microbes}, volume = {14}, number = {1}, pages = {2070392}, pmid = {35549618}, issn = {1949-0984}, mesh = {Adult ; Aged ; Aging ; Feces/microbiology ; *Gastrointestinal Microbiome/genetics ; Humans ; Male ; Metabolome ; Metagenomics ; Singapore ; Young Adult ; }, abstract = {The age-associated alterations in microbiomes vary across populations due to the influence of genetics and lifestyles. To the best of our knowledge, the microbial changes associated with aging have not yet been investigated in Singapore adults. We conducted shotgun metagenomic sequencing of fecal and saliva samples, as well as fecal metabolomics to characterize the gut and oral microbial communities of 62 healthy adult male Singaporeans, including 32 young subjects (age, 23.1 ± 1.4 years) and 30 elderly subjects (age, 69.0 ± 3.5 years). We identified 8 gut and 13 oral species that were differentially abundant in elderly compared to young subjects. By combining the gut and oral microbiomes, 25 age-associated oral-gut species connections were identified. Moreover, oral bacteria Acidaminococcus intestine and Flavonifractor plautii were less prevalent/abundant in elderly gut samples than in young gut samples, whereas Collinsella aerofaciens and Roseburia hominis showed the opposite trends. These results indicate the varied gut-oral communications with aging. Subsequently, we expanded the association studies on microbiome, metabolome and host phenotypic parameters. In particular, Eubacterium eligens increased in elderly compared to young subjects, and was positively correlated with triglycerides, which implies that the potential role of E. eligens in lipid metabolism is altered during the aging process. Our results demonstrated aging-associated changes in the gut and oral microbiomes, as well as the connections between metabolites and host-microbe interactions, thereby deepening the understanding of alterations in the human microbiome during the aging process in a Singapore population.}, }
@article {pmid35538552, year = {2022}, author = {van Best, N and Dominguez-Bello, MG and Hornef, MW and Jašarević, E and Korpela, K and Lawley, TD}, title = {Should we modulate the neonatal microbiome and what should be the goal?.}, journal = {Microbiome}, volume = {10}, number = {1}, pages = {74}, pmid = {35538552}, issn = {2049-2618}, support = {K01 DK121734/DK/NIDDK NIH HHS/United States ; }, mesh = {*Gastrointestinal Microbiome ; Goals ; *Microbiota ; }, }
@article {pmid35536453, year = {2022}, author = {Sexton, RE and Uddin, MH and Bannoura, S and Khan, HY and Mzannar, Y and Li, Y and Aboukameel, A and Al-Hallak, MN and Al-Share, B and Mohamed, A and Nagasaka, M and El-Rayes, B and Azmi, AS}, title = {Correction to: Connecting the human microbiome and pancreatic cancer.}, journal = {Cancer metastasis reviews}, volume = {41}, number = {2}, pages = {333}, doi = {10.1007/s10555-022-10037-3}, pmid = {35536453}, issn = {1573-7233}, }
@article {pmid35536037, year = {2022}, author = {Hu, C and Beyda, ND and Garey, KW}, title = {A Vancomycin HPLC Assay for Use in Gut Microbiome Research.}, journal = {Microbiology spectrum}, volume = {10}, number = {3}, pages = {e0168821}, pmid = {35536037}, issn = {2165-0497}, support = {U01 AI124290/AI/NIAID NIH HHS/United States ; }, mesh = {Anti-Bacterial Agents ; Chromatography, High Pressure Liquid/methods ; *Gastrointestinal Microbiome ; Humans ; Reproducibility of Results ; *Vancomycin/pharmacokinetics ; }, abstract = {The human microbiome project has revolutionized our understanding of the interaction between commensal microbes and human health. By far, the biggest perturbation of the microbiome involves use of broad-spectrum antibiotics excreted in the gut. Thus, pharmacodynamics of microbiome changes in relation to drug exposure pharmacokinetics is an emerging field. However, reproducibility studies are necessary to develop the field. A simple and fast high-performance liquid chromatography-photodiode array detector (HPLC) method was validated for quantitative fecal vancomycin analysis. Reproducibility of results were tested based on sample storage time, homogeneity of antibiotic within stool, and concentration consistency after lyophilization. The HPLC method enabled the complete elution of vancomycin within ~4.2 min on the reversed-phase C18 column under the isocratic elution mode, with excellent recovery (85% to 110%) over a 4-log, quantitative range (0.4-100 μg/mL). Relative standard derivations (RSD) of intra-day and inter-day results ranged from 0.4% to 5.4%. Using sample stool aliquots of various weights consistently demonstrated similar vancomycin concentrations (mean RSD: 6%; range: 2-16%). After correcting for water concentrations, vancomycin concentrations obtained after lyophilization were similar to the concentrations obtained from the original samples (RSD less than 10%). These methodologies establish sample condition standards for a quantitative HPLC to enable vancomycin pharmacokinetic studies with the human microbiome. IMPORTANCE Research on antibiotic effect on the gut microbiome is an emerging field with standardization of research methods needed. In this study, a simple and fast high-performance liquid chromatography method was validated for quantitative fecal vancomycin analysis. Reproducibility of results were tested to standardize storage time, homogeneity of antibiotic within stool, and concentration consistency after lyophilization. These methodologies establish sample condition standards for a quantitative HPLC to enable vancomycin pharmacokinetic studies with the human microbiome.}, }
@article {pmid35536006, year = {2022}, author = {Oliver, A and Xue, Z and Villanueva, YT and Durbin-Johnson, B and Alkan, Z and Taft, DH and Liu, J and Korf, I and Laugero, KD and Stephensen, CB and Mills, DA and Kable, ME and Lemay, DG}, title = {Association of Diet and Antimicrobial Resistance in Healthy U.S. Adults.}, journal = {mBio}, volume = {13}, number = {3}, pages = {e0010122}, pmid = {35536006}, issn = {2150-7511}, support = {F32 HD093185/HD/NICHD NIH HHS/United States ; }, mesh = {Animals ; *Anti-Bacterial Agents/pharmacology ; Diet ; Dietary Fiber ; Drug Resistance, Bacterial/genetics ; *Gastrointestinal Microbiome ; Humans ; Phylogeny ; }, abstract = {Antimicrobial resistance (AMR) represents a significant source of morbidity and mortality worldwide, with expectations that AMR-associated consequences will continue to worsen throughout the coming decades. Since resistance to antibiotics is encoded in the microbiome, interventions aimed at altering the taxonomic composition of the gut might allow us to prophylactically engineer microbiomes that harbor fewer antibiotic resistant genes (ARGs). Diet is one method of intervention, and yet little is known about the association between diet and antimicrobial resistance. To address this knowledge gap, we examined diet using the food frequency questionnaire (FFQ; habitual diet) and 24-h dietary recalls (Automated Self-Administered 24-h [ASA24[®]] tool) coupled with an analysis of the microbiome using shotgun metagenome sequencing in 290 healthy adult participants of the United States Department of Agriculture (USDA) Nutritional Phenotyping Study. We found that aminoglycosides were the most abundant and prevalent mechanism of AMR in these healthy adults and that aminoglycoside-O-phosphotransferases (aph3-dprime) correlated negatively with total calories and soluble fiber intake. Individuals in the lowest quartile of ARGs (low-ARG) consumed significantly more fiber in their diets than medium- and high-ARG individuals, which was concomitant with increased abundances of obligate anaerobes, especially from the family Clostridiaceae, in their gut microbiota. Finally, we applied machine learning to examine 387 dietary, physiological, and lifestyle features for associations with antimicrobial resistance, finding that increased phylogenetic diversity of diet was associated with low-ARG individuals. These data suggest diet may be a potential method for reducing the burden of AMR. IMPORTANCE Antimicrobial resistance (AMR) represents a considerable burden to health care systems, with the public health community largely in consensus that AMR will be a major cause of death worldwide in the coming decades. Humans carry antibiotic resistance in the microbes that live in and on us, collectively known as the human microbiome. Diet is a powerful method for shaping the human gut microbiome and may be a tractable method for lessening antibiotic resistance, and yet little is known about the relationship between diet and AMR. We examined this relationship in healthy individuals who contained various abundances of antibiotic resistance genes and found that individuals who consumed diverse diets that were high in fiber and low in animal protein had fewer antibiotic resistance genes. Dietary interventions may be useful for lessening the burden of antimicrobial resistance and might ultimately motivate dietary guidelines which will consider how nutrition can reduce the impact of infectious disease.}, }
@article {pmid35533688, year = {2022}, author = {Joachim, A and Schwerd, T and Hölz, H and Sokollik, C and Konrad, LA and Jordan, A and Lanzersdorfer, R and Schmidt-Choudhury, A and Hünseler, C and Adam, R}, title = {[Fecal Microbiota Transfer (FMT) in Children and Adolescents - Review and statement by the GPGE microbiome working group].}, journal = {Zeitschrift fur Gastroenterologie}, volume = {60}, number = {6}, pages = {963-969}, doi = {10.1055/a-1801-0284}, pmid = {35533688}, issn = {1439-7803}, mesh = {Adolescent ; Child ; *Clostridioides difficile ; *Clostridium Infections/complications ; Dysbiosis/complications ; Fecal Microbiota Transplantation/adverse effects ; Feces ; Humans ; *Microbiota ; Treatment Outcome ; }, abstract = {The human microbiome and especially the gastrointestinal microbiota are associated with health and disease. Disturbance in the composition or function of fecal microbiota (dysbiosis) plays a role in the development of pediatric gastrointestinal diseases. Fecal microbiota transfer (FMT) is a special intervention, where microbiota are transferred from a healthy donor.In this review we describe the current state of knowledge for FMT in pediatric patients. There is satisfactory evidence concerning FMT in patients with recurrent C. difficile infection. For inflammatory bowel disease, few studies show a potential benefit.Adverse events occurred frequently in clinical studies, but were mostly mild and transient. There are hardly any data on long-term side effects of FMT, which are particularly significant for pediatrics. In practice, there is uncertainty as to which application route, dosage or frequency should be used. Legally, donor stool is considered a drug in German-speaking countries, for which no marketing authorization exists.In conclusion, knowledge about physiology, efficacy and side effects of FMT is insufficient and legal concerns complicate its implementation. More studies on this topic are needed urgently.}, }
@article {pmid35531342, year = {2022}, author = {Yeo, LF and Lee, SC and Palanisamy, UD and Khalid, B and Ayub, Q and Lim, SY and Lim, YA and Phipps, ME}, title = {The Oral, Gut Microbiota and Cardiometabolic Health of Indigenous Orang Asli Communities.}, journal = {Frontiers in cellular and infection microbiology}, volume = {12}, number = {}, pages = {812345}, pmid = {35531342}, issn = {2235-2988}, mesh = {Bacteria/genetics ; *Cardiovascular Diseases ; *Gastrointestinal Microbiome/genetics ; Humans ; *Microbiota ; RNA, Ribosomal, 16S/genetics ; }, abstract = {The Orang Asli (OA) of Malaysia have been relatively understudied where little is known about their oral and gut microbiomes. As human health is closely intertwined with the human microbiome, this study first assessed the cardiometabolic health in four OA communities ranging from urban, rural to semi-nomadic hunter-gatherers. The urban Temuan suffered from poorer cardiometabolic health while rural OA communities were undergoing epidemiological transition. The oral microbiota of the OA were characterised by sequencing the V4 region of the 16S rRNA gene. The OA oral microbiota were unexpectedly homogenous, with comparably low alpha diversity across all four communities. The rural Jehai and Temiar PP oral microbiota were enriched for uncharacterised bacteria, exhibiting potential for discoveries. This finding also highlights the importance of including under-represented populations in large cohort studies. The Temuan oral microbiota were also elevated in opportunistic pathogens such as Corynebacterium, Prevotella, and Mogibacterium, suggesting possible oral dysbiosis in these urban settlers. The semi-nomadic Jehai gut microbiota had the highest alpha diversity, while urban Temuan exhibited the lowest. Rural OA gut microbiota were distinct from urban-like microbiota and were elevated in bacteria genera such as Prevotella 2, Prevotella 9, Lachnospiraceae ND3007, and Solobacterium. Urban Temuan microbiota were enriched in Odoribacter, Blautia, Parabacetroides, Bacteroides and Ruminococcacecae UCG-013. This study brings to light the current health trend of these indigenous people who have minimal access to healthcare and lays the groundwork for future, in-depth studies in these populations.}, }
@article {pmid35518360, year = {2022}, author = {Gan, R and Zhou, F and Si, Y and Yang, H and Chen, C and Ren, C and Wu, J and Zhang, F}, title = {DBSCAN-SWA: An Integrated Tool for Rapid Prophage Detection and Annotation.}, journal = {Frontiers in genetics}, volume = {13}, number = {}, pages = {885048}, pmid = {35518360}, issn = {1664-8021}, abstract = {As an intracellular form of a bacteriophage in the bacterial host genome, a prophage usually integrates into bacterial DNA with high specificity and contributes to horizontal gene transfer (HGT). With the exponentially increasing number of microbial sequences uncovered in genomic or metagenomics studies, there is a massive demand for a tool that is capable of fast and accurate identification of prophages. Here, we introduce DBSCAN-SWA, a command line software tool developed to predict prophage regions in bacterial genomes. DBSCAN-SWA runs faster than any previous tools. Importantly, it has great detection power based on analysis using 184 manually curated prophages, with a recall of 85% compared with Phage_Finder (63%), VirSorter (74%), and PHASTER (82%) for (Multi-) FASTA sequences. Moreover, DBSCAN-SWA outperforms the existing standalone prophage prediction tools for high-throughput sequencing data based on the analysis of 19,989 contigs of 400 bacterial genomes collected from Human Microbiome Project (HMP) project. DBSCAN-SWA also provides user-friendly result visualizations including a circular prophage viewer and interactive DataTables. DBSCAN-SWA is implemented in Python3 and is available under an open source GPLv2 license from https://github.com/HIT-ImmunologyLab/DBSCAN-SWA/.}, }
@article {pmid35512567, year = {2022}, author = {Martí-Marí, O and Martínez-Gualda, B and Fernández-Barahona, I and Mills, A and Abdelnabi, R and Noppen, S and Neyts, J and Schols, D and Camarasa, MJ and Herranz, F and Gago, F and San-Félix, A}, title = {Organotropic dendrons with high potency as HIV-1, HIV-2 and EV-A71 cell entry inhibitors.}, journal = {European journal of medicinal chemistry}, volume = {237}, number = {}, pages = {114414}, doi = {10.1016/j.ejmech.2022.114414}, pmid = {35512567}, issn = {1768-3254}, mesh = {*Dendrimers/chemistry ; *Enterovirus A, Human ; *Enterovirus Infections ; *HIV Fusion Inhibitors/pharmacology ; *HIV-1 ; HIV-2 ; Humans ; Virus Internalization ; }, abstract = {We have recently described a novel family of compounds of reduced size and dual anti-HIV and anti-EV71 activity that encompasses tripodal and tetrapodal derivatives. The tripodal prototype, AL-470, has a nitro group at the focal point of the central scaffold and three attached tryptophan residues, each of which bearing an isophthaloyl moiety at the C2 position of the indole ring. A nitro to amino substitution has allowed us now to introduce a chemically addressable functionality to perform further structural modifications consisting of both direct and linker-mediated attachment of several aromatic groups, including the fluorescent dye Alexa Fluor 647 and the antibody-recruiting 2,4-dinitrophenyl motif. Some of the derivatives turned out to be more potent and selective than AL-470 against HIV-1, HIV-2 and EV-A71. The fluorescent probe demonstrated a specific tropism for intestines and lungs, two important niches for the human microbiome in health and disease.}, }
@article {pmid35509426, year = {2022}, author = {Ianiro, G and Iorio, A and Porcari, S and Masucci, L and Sanguinetti, M and Perno, CF and Gasbarrini, A and Putignani, L and Cammarota, G}, title = {How the gut parasitome affects human health.}, journal = {Therapeutic advances in gastroenterology}, volume = {15}, number = {}, pages = {17562848221091524}, pmid = {35509426}, issn = {1756-283X}, abstract = {The human gut microbiome (GM) is a complex ecosystem that includes numerous prokaryotic and eukaryotic inhabitants. The composition of GM can influence an array of host physiological functions including immune development. Accumulating evidence suggest that several members of non-bacterial microbiota, including protozoa and helminths, that were earlier considered as pathogens, could have a commensal or beneficial relationship with the host. Here we examine the most recent data from omics studies on prokaryota-meiofauna-host interaction as well as the impact of gut parasitome on gut bacterial ecology and its role as 'immunological driver' in health and disease to glimpse new therapeutic perspectives.}, }
@article {pmid35495663, year = {2022}, author = {Zhang, Z and Feng, Q and Li, M and Li, Z and Xu, Q and Pan, X and Chen, W}, title = {Age-Related Cancer-Associated Microbiota Potentially Promotes Oral Squamous Cell Cancer Tumorigenesis by Distinct Mechanisms.}, journal = {Frontiers in microbiology}, volume = {13}, number = {}, pages = {852566}, pmid = {35495663}, issn = {1664-302X}, abstract = {The oral squamous cell cancer (OSCC) incidence in young patients has increased since the end of the last century; however, the underlying mechanism is still unclear. Oral microbiota dysbiosis was proven to be a tumorigenesis factor, and we propose that there is a distinct bacterial composition in young patients that facilitates the progression of OSCC. Twenty elderly (>60 years old) and 20 young (<50 years old) subjects were included in this study. OSCC tissue was collected during surgery, sent for 16S rDNA sequencing and analyzed by the QIIME 2 pipeline. The results showed that Ralstonia, Prevotella, and Ochrobactrum were significantly enriched in younger OSCC tissue microbiota, while Pedobacter was more abundant in elderly OSCC tissues. Fusobacterium had high relative abundance in both cohorts. At the phylum level, Proteobacteria was the dominant taxon in all samples. The functional study showed that there were significant differences in the taxa abundance from metabolic and signaling pathways. The results indicated that the microbiota of younger OSCC tissues differed from that of elderly OSCC tissues by both taxon composition and function, which partially explains the distinct roles of bacteria during tumorigenesis in these two cohorts. These findings provide insights into different mechanisms of the microbiota-cancer relationship with regard to aging.}, }
@article {pmid35495638, year = {2022}, author = {Jian, C and Kanerva, S and Qadri, S and Yki-Järvinen, H and Salonen, A}, title = {In vitro Effects of Bacterial Exposure on Secretion of Zonulin Family Peptides and Their Detection in Human Tissue Samples.}, journal = {Frontiers in microbiology}, volume = {13}, number = {}, pages = {848128}, pmid = {35495638}, issn = {1664-302X}, abstract = {Commercially available ELISAs for zonulin (pre-haptoglobin 2), a protein with tight junction regulatory activity in the epithelia, were recently shown to recognize other proteins that are structurally and functionally related to zonulin, termed zonulin family peptides (ZFPs). With little or no information about the identity and property of ZFPs, various commercial zonulin ELISA kits are widely utilized in research as a marker of intestinal permeability. Bacterial exposure is a known trigger for the secretion of zonulin, but it remains unclear whether distinct bacteria differ in their capability to stimulate zonulin secretion. We hypothesized that ZFPs are similar to zonulin regarding response to bacterial exposure and aimed to compare the effects of non-pathogenic, Gram-negative bacteria (Escherichia coli RY13 and E. coli K12 DH5α) and probiotic, Gram-positive bacteria (Lactobacillus rhamnosus GG and Bifidobacterium bifidum) on ZFP secretion in an in vitro model. Additionally, utilizing samples from human clinical trials, we correlated circulating levels of ZFPs to the gut bacteria and determined the presence of ZFPs in various human tissues. Unexpectedly, we found that the ZFPs quantified by the widely used IDK® Zonulin ELISA kits are specifically triggered by the exposure to live Lactobacillus rhamnosus GG in HT-29 cells, associated with absolute abundances of intestinal Lactobacillus and Bifidobacterium in adults, and are copious in the small intestine but undetectable in the liver or adipose tissue. These characteristics appear to be different from zonulin and highlight the need for further characterization of ZFPs recognized by commercially available and widely used "zonulin" ELISAs.}, }
@article {pmid35480328, year = {2022}, author = {Nkera-Gutabara, CK and Kerr, R and Scholefield, J and Hazelhurst, S and Naidoo, J}, title = {Microbiomics: The Next Pillar of Precision Medicine and Its Role in African Healthcare.}, journal = {Frontiers in genetics}, volume = {13}, number = {}, pages = {869610}, pmid = {35480328}, issn = {1664-8021}, abstract = {Limited access to technologies that support early monitoring of disease risk and a poor understanding of the geographically unique biological and environmental factors underlying disease, represent significant barriers to improved health outcomes and precision medicine efforts in low to middle income countries. These challenges are further compounded by the rich genetic diversity harboured within Southern Africa thus necessitating alternative strategies for the prediction of disease risk and clinical outcomes in regions where accessibility to personalized healthcare remains limited. The human microbiome refers to the community of microorganisms (bacteria, archaea, fungi and viruses) that co-inhabit the human body. Perturbation of the natural balance of the gut microbiome has been associated with a number of human pathologies, and the microbiome has recently emerged as a critical determinant of drug pharmacokinetics and immunomodulation. The human microbiome should therefore not be omitted from any comprehensive effort towards stratified healthcare and would provide an invaluable and orthogonal approach to existing precision medicine strategies. Recent studies have highlighted the overarching effect of geography on gut microbial diversity as it relates to human health. Health insights from international microbiome datasets are however not yet verified in context of the vast geographical diversity that exists throughout the African continent. In this commentary we discuss microbiome research in Africa and its role in future precision medicine initiatives across the African continent.}, }
@article {pmid35479632, year = {2022}, author = {Vilne, B and Ķibilds, J and Siksna, I and Lazda, I and Valciņa, O and Krūmiņa, A}, title = {Could Artificial Intelligence/Machine Learning and Inclusion of Diet-Gut Microbiome Interactions Improve Disease Risk Prediction? Case Study: Coronary Artery Disease.}, journal = {Frontiers in microbiology}, volume = {13}, number = {}, pages = {627892}, pmid = {35479632}, issn = {1664-302X}, abstract = {Coronary artery disease (CAD) is the most common cardiovascular disease (CVD) and the main leading cause of morbidity and mortality worldwide, posing a huge socio-economic burden to the society and health systems. Therefore, timely and precise identification of people at high risk of CAD is urgently required. Most current CAD risk prediction approaches are based on a small number of traditional risk factors (age, sex, diabetes, LDL and HDL cholesterol, smoking, systolic blood pressure) and are incompletely predictive across all patient groups, as CAD is a multi-factorial disease with complex etiology, considered to be driven by both genetic, as well as numerous environmental/lifestyle factors. Diet is one of the modifiable factors for improving lifestyle and disease prevention. However, the current rise in obesity, type 2 diabetes (T2D) and CVD/CAD indicates that the "one-size-fits-all" approach may not be efficient, due to significant variation in inter-individual responses. Recently, the gut microbiome has emerged as a potential and previously under-explored contributor to these variations. Hence, efficient integration of dietary and gut microbiome information alongside with genetic variations and clinical data holds a great promise to improve CAD risk prediction. Nevertheless, the highly complex nature of meals combined with the huge inter-individual variability of the gut microbiome poses several Big Data analytics challenges in modeling diet-gut microbiota interactions and integrating these within CAD risk prediction approaches for the development of personalized decision support systems (DSS). In this regard, the recent re-emergence of Artificial Intelligence (AI) / Machine Learning (ML) is opening intriguing perspectives, as these approaches are able to capture large and complex matrices of data, incorporating their interactions and identifying both linear and non-linear relationships. In this Mini-Review, we consider (1) the most used AI/ML approaches and their different use cases for CAD risk prediction (2) modeling of the content, choice and impact of dietary factors on CAD risk; (3) classification of individuals by their gut microbiome composition into CAD cases vs. controls and (4) modeling of the diet-gut microbiome interactions and their impact on CAD risk. Finally, we provide an outlook for putting it all together for improved CAD risk predictions.}, }
@article {pmid35475626, year = {2022}, author = {Oliver, A and El Alaoui, K and Haunschild, C and Avelar-Barragan, J and Mendez Luque, LF and Whiteson, K and Fleischman, AG}, title = {Fecal Microbial Community Composition in Myeloproliferative Neoplasm Patients Is Associated with an Inflammatory State.}, journal = {Microbiology spectrum}, volume = {10}, number = {3}, pages = {e0003222}, pmid = {35475626}, issn = {2165-0497}, support = {P30 CA062203/CA/NCI NIH HHS/United States ; T32 CA060396/CA/NCI NIH HHS/United States ; }, mesh = {Chronic Disease ; Feces ; *Gastrointestinal Microbiome ; Humans ; Inflammation ; *Myeloproliferative Disorders/pathology ; *Neoplasms ; }, abstract = {The capacity of the human microbiome to modulate inflammation in the context of cancer is becoming increasingly clear. Myeloproliferative neoplasms (MPNs) are chronic hematologic malignancies in which inflammation plays a key role in disease initiation, progression, and symptomatology. To better understand the composition of the gut microbiome in patients with MPN, triplicate fecal samples were collected from 25 MPN patients and 25 non-MPN controls. Although most of the variance between the microbial community compositions could be attributed to the individual (permutational analysis of variance [PERMANOVA], R[2] = 0.92, P = 0.001), 1.7% of the variance could be attributed to disease status (MPN versus non-MPN). When a more detailed analysis was performed, significantly fewer reads mapping to a species of Phascolarctobacterium, a microbe previously associated with reduced inflammation, were found in MPNs. Further, our data revealed an association between Parabacteroides and tumor necrosis factor alpha (TNF-α), an inflammatory cytokine elevated in MPNs. Taken together, our results indicate a significant difference in the microbiome of MPN patients compared to non-MPN controls, and we identify specific species which may have a role in the chronic inflammation central to this disease. IMPORTANCE MPNs are chronic blood cancers in which inflammation plays a key role in disease initiation, progression, and symptomatology. The gut microbiome modulates normal blood development and inflammation and may also impact the development and manifestation of blood cancers. Therefore, the microbiome may be an important modulator of inflammation in MPN and could potentially be leveraged therapeutically in this disease. However, the relationship between the gut microbiome and MPNs has not been defined. Therefore, we performed an evaluation of the MPN microbiome, comparing the microbiomes of MPN patients with healthy donors and between MPN patients with various states of disease.}, }
@article {pmid35466418, year = {2022}, author = {Mishra, AK and Müller, CL}, title = {Negative binomial factor regression with application to microbiome data analysis.}, journal = {Statistics in medicine}, volume = {41}, number = {15}, pages = {2786-2803}, pmid = {35466418}, issn = {1097-0258}, mesh = {*Data Analysis ; Factor Analysis, Statistical ; Feeding Behavior ; Gastrointestinal Microbiome ; Humans ; Life Style ; *Microbiota ; Regression Analysis ; United States ; }, abstract = {The human microbiome provides essential physiological functions and helps maintain host homeostasis via the formation of intricate ecological host-microbiome relationships. While it is well established that the lifestyle of the host, dietary preferences, demographic background, and health status can influence microbial community composition and dynamics, robust generalizable associations between specific host-associated factors and specific microbial taxa have remained largely elusive. Here, we propose factor regression models that allow the estimation of structured parsimonious associations between host-related features and amplicon-derived microbial taxa. To account for the overdispersed nature of the amplicon sequencing count data, we propose negative binomial reduced rank regression (NB-RRR) and negative binomial co-sparse factor regression (NB-FAR). While NB-RRR encodes the underlying dependency among the microbial abundances as outcomes and the host-associated features as predictors through a rank-constrained coefficient matrix, NB-FAR uses a sparse singular value decomposition of the coefficient matrix. The latter approach avoids the notoriously difficult joint parameter estimation by extracting sparse unit-rank components of the coefficient matrix sequentially, effectively delivering interpretable bi-clusters of taxa and host-associated factors. To solve the nonconvex optimization problems associated with these factor regression models, we present a novel iterative block-wise majorization procedure. Extensive simulation studies and an application to the microbial abundance data from the American Gut Project (AGP) demonstrate the efficacy of the proposed procedure. In the AGP data, we identify several factors that strongly link dietary habits and host life style to specific microbial families.}, }
@article {pmid35461664, year = {2022}, author = {Dash, HR and Das, S}, title = {Microbial community signatures for estimation of postmortem time intervals.}, journal = {Advances in applied microbiology}, volume = {118}, number = {}, pages = {91-113}, doi = {10.1016/bs.aambs.2022.02.002}, pmid = {35461664}, issn = {0065-2164}, mesh = {Autopsy ; Cadaver ; Humans ; *Microbiota ; *Postmortem Changes ; }, abstract = {The human body provides a complex ecosystem for symbiotic habitation of a huge number of microorganisms. These commensal microorganisms provide a huge benefit to the living host by acting against many deadly infections. Once the host dies, many changes in the complex ecosystem of the human body take place. The personalized microbes of a human body undergo successional change as many exogenous microbes attack the nutrient-rich cadaver after death. The succession pattern change of microbes in human cadaver allows postulating different models for estimation of Postmortem time interval (PMI). Estimation of PMI has a broad prospect from the criminal investigation point of view. Though many techniques are being used nowadays to estimate PMI, all of them have their pros and cons. With the advent of advanced molecular biological techniques, studies on the thanatomicrobiome of a human cadaver have gained pace and provide a superior alternative for conventional methods of PMI estimation. This chapter summarizes the recent advancements in the changes in signature microflora postmortem with change in human microenvironment to postulate a consensus model for estimation of PMI.}, }
@article {pmid35459927, year = {2022}, author = {Ventin-Holmberg, R and Höyhtyä, M and Saqib, S and Korpela, K and Nikkonen, A and Salonen, A and de Vos, WM and Kolho, KL}, title = {The gut fungal and bacterial microbiota in pediatric patients with inflammatory bowel disease introduced to treatment with anti-tumor necrosis factor-α.}, journal = {Scientific reports}, volume = {12}, number = {1}, pages = {6654}, pmid = {35459927}, issn = {2045-2322}, mesh = {Bacteria/genetics ; Child ; *Crohn Disease/drug therapy ; *Gastrointestinal Microbiome ; Humans ; *Inflammatory Bowel Diseases/drug therapy/microbiology ; Infliximab/therapeutic use ; Leukocyte L1 Antigen Complex ; *Tumor Necrosis Factor-alpha/drug effects/therapeutic use ; }, abstract = {Pediatric inflammatory bowel disease (PIBD) is a globally increasing chronic inflammatory disease associated with an imbalanced intestinal microbiota and treated with several treatment options, including anti-tumor necrosis factor alpha (TNF-α), such as infliximab (IFX). Up to half of the patients do not respond to the drug and there are no methods for response prediction. Our aim was to predict IFX response from the gut microbiota composition since this is largely unexplored in PIBD. The gut microbiota of 30 PIBD patients receiving IFX was studied by MiSeq sequencing targeting 16S and ITS region from fecal samples collected before IFX and two and six weeks after the start of treatment. The response to IFX induction was determined by fecal calprotectin value < 100 µg/g at week six. The bacterial microbiota differed significantly between response groups, with higher relative abundance of butyrate-producing bacteria in responders compared to non-responders at baseline, validated by high predictive power (area under curve = 0.892) for baseline Ruminococcus and calprotectin. Additionally, non-responders had higher abundance of Candida, while responders had higher abundance of Saccharomyces at the end of the study. The gut microbiota composition in PIBD patients could predict response to IFX treatment in the future.}, }
@article {pmid35458152, year = {2022}, author = {Warner, JO and Warner, JA}, title = {The Foetal Origins of Allergy and Potential Nutritional Interventions to Prevent Disease.}, journal = {Nutrients}, volume = {14}, number = {8}, pages = {}, pmid = {35458152}, issn = {2072-6643}, mesh = {Animals ; Breast Feeding ; Cattle ; Diet ; Female ; Humans ; *Hypersensitivity ; Infant ; Lactation ; Milk ; Pregnancy ; }, abstract = {The first nine months from conception to birth involves greater changes than at any other time in life, affecting organogenesis, endocrine, metabolic and immune programming. It has led to the concept that the "first 1000 days" from conception to the second birthday are critical in establishing long term health or susceptibility to disease. Immune ontogeny is predominantly complete within that time and is influenced by the maternal genome, health, diet and environment pre-conception and during pregnancy and lactation. Components of the immunological protection of the pregnancy is the generation of Th-2 and T-regulatory cytokines with the consequence that neonatal adaptive responses are also biased towards Th-2 (allergy promoting) and T-regulatory (tolerance promoting) responses. Normally after birth Th-1 activity increases while Th-2 down-regulates and the evolving normal human microbiome likely plays a key role. This in turn will have been affected by maternal health, diet, exposure to antibiotics, mode of delivery, and breast or cow milk formula feeding. Complex gene/environment interactions affect outcomes. Many individual nutrients affect immune mechanisms and variations in levels have been associated with susceptibility to allergic disease. However, intervention trials employing single nutrient supplementation to prevent allergic disease have not achieved the expected outcomes suggested by observational studies. Investigation of overall dietary practices including fresh fruit and vegetables, fish, olive oil, lower meat intake and home cooked foods as seen in the Mediterranean and other healthy diets have been associated with reduced prevalence of allergic disease. This suggests that the "soup" of overall nutrition is more important than individual nutrients and requires further investigation both during pregnancy and after the infant has been weaned. Amongst all the potential factors affecting allergy outcomes, modification of maternal and infant nutrition and the microbiome are easier to employ than changing other aspects of the environment but require large controlled trials before recommending changes to current practice.}, }
@article {pmid35457956, year = {2022}, author = {Wang, S and Alenius, H and El-Nezami, H and Karisola, P}, title = {A New Look at the Effects of Engineered ZnO and TiO2 Nanoparticles: Evidence from Transcriptomics Studies.}, journal = {Nanomaterials (Basel, Switzerland)}, volume = {12}, number = {8}, pages = {}, pmid = {35457956}, issn = {2079-4991}, support = {307768//Academy of Finland/ ; }, abstract = {Titanium dioxide (TiO2) and zinc oxide (ZnO) nanoparticles (NPs) have attracted a great deal of attention due to their excellent electrical, optical, whitening, UV-adsorbing and bactericidal properties. The extensive production and utilization of these NPs increases their chances of being released into the environment and conferring unintended biological effects upon exposure. With the increasingly prevalent use of the omics technique, new data are burgeoning which provide a global view on the overall changes induced by exposures to NPs. In this review, we provide an account of the biological effects of ZnO and TiO2 NPs arising from transcriptomics in in vivo and in vitro studies. In addition to studies on humans and mice, we also describe findings on ecotoxicology-related species, such as Danio rerio (zebrafish), Caenorhabditis elegans (nematode) or Arabidopsis thaliana (thale cress). Based on evidence from transcriptomics studies, we discuss particle-induced biological effects, including cytotoxicity, developmental alterations and immune responses, that are dependent on both material-intrinsic and acquired/transformed properties. This review seeks to provide a holistic insight into the global changes induced by ZnO and TiO2 NPs pertinent to human and ecotoxicology.}, }
@article {pmid35456813, year = {2022}, author = {Vera-Urbina, F and Dos Santos-Torres, MF and Godoy-Vitorino, F and Torres-Hernández, BA}, title = {The Gut Microbiome May Help Address Mental Health Disparities in Hispanics: A Narrative Review.}, journal = {Microorganisms}, volume = {10}, number = {4}, pages = {}, pmid = {35456813}, issn = {2076-2607}, support = {5U54MD007600/MD/NIMHD NIH HHS/United States ; 5P20GM103642/GM/NIGMS NIH HHS/United States ; }, abstract = {The gut-brain axis is the biological connection between the enteric and the central nervous systems. Given the expansion of the microbial sciences with the new human microbiome field facilitated by the decrease in sequencing costs, we now know more about the role of gut microbiota in human health. In this short review, particular focus is given to the gut-brain axis and its role in psychiatric diseases such as anxiety and depression. Additionally, factors that contribute to changes in the gut-brain axis, including the gut microbiome, nutrition, the host's genome, and ethnic difference, are highlighted. Emphasis is given to the lack of studies on Hispanic populations, despite the fact this ethnic group has a higher prevalence of anxiety and depression in the US.}, }
@article {pmid35454968, year = {2022}, author = {Hu, C and Rzymski, P}, title = {Non-Photosynthetic Melainabacteria (Cyanobacteria) in Human Gut: Characteristics and Association with Health.}, journal = {Life (Basel, Switzerland)}, volume = {12}, number = {4}, pages = {}, pmid = {35454968}, issn = {2075-1729}, abstract = {Gut microorganisms are comprised of thousands of species and play an important role in the host's metabolism, overall health status, and risk of disease. Recently, the discovery of non-photosynthetic cyanobacteria (class "Melainabacteria") in the human and animal gut triggered a broad interest in studying cyanobacteria's evolution, physiology, and ecological relevance of the Melainabacteria members. In the present paper, we review the general characteristics of Melainabacteria, their phylogeny, distribution, and ecology. The potential link between these microorganisms and human health is also discussed based on available human-microbiome studies. Their abundance tends to increase in patients with selected neurodegenerative, gastrointestinal, hepatic, metabolic, and respiratory diseases. However, the available evidence is correlative and requires further longitudinal studies. Although the research on Melainabacteria in the human gut is still in its infancy, elucidation of their role appears important in better understanding microbiome-human health interactions. Further studies aiming to identify particular gut cyanobacteria species, culture them in vitro, and characterize them on the molecular, biochemical, and physiological levels are encouraged.}, }
@article {pmid35453183, year = {2022}, author = {Agosta, M and Bencardino, D and Argentieri, M and Pansani, L and Sisto, A and Ciofi Degli Atti, ML and D'Amore, C and Putignani, L and Bagolan, P and Iacobelli, BD and Dotta, A and Martini, L and Di Chiara, L and Magnani, M and Perno, CF and Andreoni, F and Bernaschi, P}, title = {Prevalence and Molecular Typing of Carbapenemase-Producing Enterobacterales among Newborn Patients in Italy.}, journal = {Antibiotics (Basel, Switzerland)}, volume = {11}, number = {4}, pages = {}, pmid = {35453183}, issn = {2079-6382}, abstract = {The spread of carbapenemase-producing Enterobacterales (CPE), especially Klebsiella pneumoniae (K. pneumoniae) and Escherichia coli (E. coli), is a serious public health threat in pediatric hospitals. The associated risk in newborns is due to their underdeveloped immune system and limited treatment options. The aim was to estimate the prevalence and circulation of CPE among the neonatal intensive units of a major pediatric hospital in Italy and to investigate their molecular features. A total of 124 CPE were isolated from rectal swabs of 99 newborn patients at Bambino Gesù Children's Hospital between July 2016 and December 2019. All strains were characterized by antimicrobial susceptibility testing, detection of resistance genes, and PCR-based replicon typing (PBRT). One strain for each PBRT profile of K. pneumoniae or E. coli was characterized by multilocus-sequence typing (MLST). Interestingly, the majority of strains were multidrug-resistant and carried the blaNDM gene. A large part was characterized by a multireplicon status, and FII, A/C, FIA (15%) was the predominant. Despite the limited size of collection, MLST analysis revealed a high number of Sequence Types (STs): 14 STs among 28 K. pneumoniae and 8 STs among 11 E. coli, with the prevalence of the well-known clones ST307 and ST131, respectively. This issue indicated that some strains shared the same circulating clone. We identified a novel, so far never described, ST named ST10555, found in one E. coli strain. Our investigation showed a high heterogeneity of CPE circulating among neonatal units, confirming the need to monitor their dissemination in the hospital also through molecular methods.}, }
@article {pmid35452382, year = {2022}, author = {Hua, X and Cao, Y and Morgan, DM and Miller, K and Chin, SM and Bellavance, D and Khalili, H}, title = {Longitudinal analysis of the impact of oral contraceptive use on the gut microbiome.}, journal = {Journal of medical microbiology}, volume = {71}, number = {4}, pages = {}, doi = {10.1099/jmm.0.001512}, pmid = {35452382}, issn = {1473-5644}, mesh = {Child, Preschool ; Contraceptives, Oral/pharmacology ; Estradiol ; Female ; *Gastrointestinal Microbiome ; Gonadal Steroid Hormones ; Humans ; Testosterone ; }, abstract = {Introduction. Evidence has linked exogenous and endogenous sex hormones with the human microbiome.Hypothesis/Gap statement. The longitudinal effects of oral contraceptives (OC) on the human gut microbiome have not previously been studied.Aim. We sought to examine the longitudinal impact of OC use on the taxonomic composition and metabolic functions of the gut microbiota and endogenous sex steroid hormones after initiation of OC use.Methodology. We recruited ten healthy women who provided blood and stool samples prior to OC use, 1 month and 6 months after starting OC. We measured serum levels of sex hormones, including estradiol, progesterone, sex hormone-binding globulin (SHBG), and total testosterone. Shotgun metagenomic sequencing was performed on DNA extracted from faecal samples. Species and metabolic pathway abundances were determined using MetaPhlAn2 and HUMAnN2. Multivariate association with linear models was used to identify microbial species and metabolic pathways associated with OC use and endogenous levels of sex hormones.Results. The percentage variance of the microbial community explained by individual factors ranged from 9.9 % for age to 2.7 % for time since initiation of OC use. We observed no changes in the diversity or composition of the gut microbiome following OC initiation. However, the relative abundance of the biosynthesis pathways of peptidoglycan, amino acids (lysine, threonine, methionine, and tryptophan), and the NAD salvage pathway increased after OC initiation. In addition, serum levels of estradiol and SHBG were positively associated with Eubacterium ramulus, a flavonoid-degrading bacterium. Similarly, microbes involving biosynthesis of l-lysine, l-threonine, and l-methionine were significantly associated with lower estradiol, SHBG, and higher levels of total testosterone.Conclusion. Our study provides the first piece of evidence supporting the association between exogenous and endogenous sex hormones and gut microbiome composition and function.}, }
@article {pmid35452117, year = {2022}, author = {Garcia-Vello, P and Tytgat, HLP and Gray, J and Elzinga, J and Di Lorenzo, F and Biboy, J and Vollmer, D and De Castro, C and Vollmer, W and de Vos, WM and Molinaro, A}, title = {Peptidoglycan from Akkermansia muciniphila MucT: chemical structure and immunostimulatory properties of muropeptides.}, journal = {Glycobiology}, volume = {32}, number = {8}, pages = {712-719}, doi = {10.1093/glycob/cwac027}, pmid = {35452117}, issn = {1460-2423}, support = {BB/R017409/1//BBSRC/ ; }, mesh = {Akkermansia ; Animals ; *Gastrointestinal Microbiome ; Humans ; Mice ; *Peptidoglycan ; Verrucomicrobia/physiology ; }, abstract = {Akkermansia muciniphila is an intestinal symbiont known to improve the gut barrier function in mice and humans. Various cell envelope components have been identified to play a critical role in the immune signaling of A. muciniphila, but the chemical composition and role of peptidoglycan (PG) remained elusive. Here, we isolated PG fragments from A. muciniphila MucT (ATCC BAA-835), analyzed their composition and evaluated their immune signaling capacity. Structurally, the PG of A. muciniphila was found to be noteworthy due of the presence of some nonacetylated glucosamine residues, which presumably stems from deacetylation of N-acetylglucosamine. Some of the N-acetylmuramic acid (MurNAc) subunits were O-acetylated. The immunological assays revealed that muropeptides released from the A. muciniphila PG could both activate the intracellular NOD1 and NOD2 receptors to a comparable extent as muropeptides from Escherichia coli BW25113. These data challenge the hypothesis that non-N-acetylattion of PG can be used as a NOD-1 evasion mechanism. Our results provide new insights into the diversity of cell envelope structures of key gut microbiota members and their role in steering host-microbiome interactions.}, }
@article {pmid35448562, year = {2022}, author = {Ventin-Holmberg, R and Saqib, S and Korpela, K and Nikkonen, A and Peltola, V and Salonen, A and de Vos, WM and Kolho, KL}, title = {The Effect of Antibiotics on the Infant Gut Fungal Microbiota.}, journal = {Journal of fungi (Basel, Switzerland)}, volume = {8}, number = {4}, pages = {}, pmid = {35448562}, issn = {2309-608X}, support = {TYH2021216, 308255//Pediatric Research Foundation (Finland), Helsinki University Hospital Research Fund and Academy of Finland/ ; }, abstract = {Antibiotics are commonly used drugs in infants, causing disruptions in the developing gut microbiota with possible detrimental long-term effects such as chronic inflammatory diseases. The focus has been on bacteria, but research shows that fungi might have an important role as well. There are only a few studies on the infant gut fungal microbiota, the mycobiota, in relation to antibiotic treatment. Here, the aim was to investigate the impact of antibiotics on the infant gut mycobiota, and the interkingdom associations between bacteria and fungi. We had 37 antibiotic-naïve patients suffering from respiratory syncytial virus, of which 21 received one to four courses of antibiotics due to complications, and 16 remained antibiotic-naïve throughout the study. Fecal samples were collected before, during and after antibiotic treatment with a follow-up period of up to 9.5 months. The gut mycobiota was studied by Illumina MiSeq sequencing of the ITS1 region. We found that antibiotic use affected the gut mycobiota, most prominently seen as a higher relative abundance of Candida (p < 0.001), and a higher fungal diversity (p = 0.005−0.04) and richness (p = 0.03) in the antibiotic-treated infants compared to the antibiotic-naïve ones at multiple timepoints. This indicates that the gut mycobiota could contribute to the long-term consequences of antibiotic treatments.}, }
@article {pmid35448490, year = {2022}, author = {Abot, A and Brochot, A and Pomié, N and Wemelle, E and Druart, C and Régnier, M and Delzenne, NM and de Vos, WM and Knauf, C and Cani, PD}, title = {Camu-Camu Reduces Obesity and Improves Diabetic Profiles of Obese and Diabetic Mice: A Dose-Ranging Study.}, journal = {Metabolites}, volume = {12}, number = {4}, pages = {}, pmid = {35448490}, issn = {2218-1989}, support = {ANR-18-CE14-0007-01//Agence Nationale de la Recherche/ ; IRP NeuroMicrobiota//Inserm/ ; A-Mansia Biotech S.A. grant//A-Mansia Biotech S.A./ ; Walloon Region grant//Walloon Region/ ; FRS-FNRS grant//Fund for Scientific Research/ ; }, abstract = {Overweight, obesity, and their comorbidities are currently considered a major public health concern. Today considerable efforts are still needed to develop efficient strategies able to attenuate the burden of these diseases. Nutritional interventions, some with plant extracts, present promising health benefits. In this study, we evaluated the action of Camu-Camu (Myrciaria dubia), an Amazonian fruit rich in polyphenols and vitamin C, on the prevention of obesity and associated disorders in mice and the abundance of Akkermansia muciniphila in both cecum and feces. Methods: We investigated the dose-response effects of Camu-Camu extract (CCE) in the context of high-fat-diet (HFD)-induced obesity. After 5 weeks of supplementation, we demonstrated that the two doses of CCE differently improved glucose and lipid homeostasis. The lowest CCE dose (62.5 mg/kg) preferentially decreased non-HDL cholesterol and free fatty acids (FFA) and increased the abundance of A. muciniphila without affecting liver metabolism, while only the highest dose of CCE (200 mg/kg) prevented excessive body weight gain, fat mass gain, and hepatic steatosis. Both doses decreased fasting hyperglycemia induced by HFD. In conclusion, the use of plant extracts, and particularly CCE, may represent an additional option in the support of weight management strategies and glucose homeostasis alteration by mechanisms likely independent from the modulation of A. muciniphila abundance.}, }
@article {pmid35447322, year = {2022}, author = {Patjas, A and Kantele, A}, title = {International travel and travelers' diarrhea - Increased risk of urinary tract infection.}, journal = {Travel medicine and infectious disease}, volume = {48}, number = {}, pages = {102331}, doi = {10.1016/j.tmaid.2022.102331}, pmid = {35447322}, issn = {1873-0442}, mesh = {Diarrhea/prevention &amp; control ; Female ; Humans ; Male ; Prospective Studies ; Risk Factors ; *Travel ; *Urinary Tract Infections/epidemiology ; }, abstract = {BACKGROUND: Urinary tract infections (UTIs) rank among the most common infections encountered in health care, with an annual incidence of 12% for women. Despite the vast numbers of international travels (over 1.5 billion annually), no prospective studies have had primary focus on UTIs during travel.<br><br>METHODS: We recruited in 2008-17 international travelers who all filled out pre- and post-travel questionnaires. Incidence rates of UTI were calculated separately for both sexes. Multivariable analyses were conducted to identify risk factors for UTI during travel.<br><br>RESULTS: In total 15/517 (2,9%) travelers acquired UTI during travel, yielding an annual incidence of 62% for female and 18% for male travelers. Travelers' diarrhea (TD) was identified as a factor predisposing to UTI (OR 9.2, 95% CI 1.5-+&#x221e;, p&#xa0;=&#xa0;0.011); all UTI cases were recorded by travelers with TD.<br><br>CONCLUSIONS: To our knowledge, this is the first prospective study with a primary focus on UTI during travel. Our data reveal that among travelers the incidence of UTI far exceeds that reported for the general population. TD was identified as a major risk factor for the infection. Our results suggest TD prevention as a means of also preventing UTI during travel.}, }
@article {pmid35446845, year = {2022}, author = {Giliberti, R and Cavaliere, S and Mauriello, IE and Ercolini, D and Pasolli, E}, title = {Host phenotype classification from human microbiome data is mainly driven by the presence of microbial taxa.}, journal = {PLoS computational biology}, volume = {18}, number = {4}, pages = {e1010066}, pmid = {35446845}, issn = {1553-7358}, mesh = {*Bacteria/genetics ; Humans ; Metagenome/genetics ; *Microbiota/genetics ; Phenotype ; RNA, Ribosomal, 16S/genetics ; }, abstract = {Machine learning-based classification approaches are widely used to predict host phenotypes from microbiome data. Classifiers are typically employed by considering operational taxonomic units or relative abundance profiles as input features. Such types of data are intrinsically sparse, which opens the opportunity to make predictions from the presence/absence rather than the relative abundance of microbial taxa. This also poses the question whether it is the presence rather than the abundance of particular taxa to be relevant for discrimination purposes, an aspect that has been so far overlooked in the literature. In this paper, we aim at filling this gap by performing a meta-analysis on 4,128 publicly available metagenomes associated with multiple case-control studies. At species-level taxonomic resolution, we show that it is the presence rather than the relative abundance of specific microbial taxa to be important when building classification models. Such findings are robust to the choice of the classifier and confirmed by statistical tests applied to identifying differentially abundant/present taxa. Results are further confirmed at coarser taxonomic resolutions and validated on 4,026 additional 16S rRNA samples coming from 30 public case-control studies.}, }
@article {pmid35444617, year = {2022}, author = {Zhang, WH and Jin, ZY and Yang, ZH and Zhang, JY and Ma, XH and Guan, J and Sun, BL and Chen, X}, title = {Fecal Microbiota Transplantation Ameliorates Active Ulcerative Colitis by Downregulating Pro-inflammatory Cytokines in Mucosa and Serum.}, journal = {Frontiers in microbiology}, volume = {13}, number = {}, pages = {818111}, pmid = {35444617}, issn = {1664-302X}, abstract = {BACKGROUND: Ulcerative colitis (UC) is a multi-factor disease characterized by alternating remission periods and repeated occurrence. It has been shown that fecal microbiota transplantation (FMT) is an emerging and effective approach for UC treatment. Since most existing studies chose adults as donors for fecal microbiota, we conducted this study to determine the long-term efficacy and safety of the microbiota from young UC patient donors and illustrate its specific physiological effects.<br><br>METHODS: Thirty active UC patients were enrolled and FMT were administered with the first colonoscopy and two subsequent enema/transendoscopic enteral tubing (TET) practical regimens in The First Affiliated Hospital of Anhui Medical University in China. Disease activity and inflammatory biomarkers were assessed 6&#x2009;weeks/over 1&#x2009;year after treatment. The occurrence of adverse events was also recorded. The samples from blood and mucosa were collected to detect the changes of inflammatory biomarkers and cytokines. The composition of gut and oral microbiota were also sampled and sequenced to confirm the alteration of microbial composition.<br><br>RESULTS: Twenty-seven patients completed the treatment, among which 16 (59.3%) achieved efficacious clinical response and 11 (40.7%) clinical remission. Full Mayo score and calprotectin dropped significantly and remained stable over 1&#x2009;year. FMT also significantly reduced the levels of C-reactive protein (CRP), interleukin-1 beta (IL-1&#x3b2;), and interleukin-6 (IL-6). The gut microbiota altered significantly with increased bacterial diversity and decreased metabolic diversity in responsive patients. The pro-inflammatory enterobacteria decreased after FMT and the abundance of Collinsella increased. Accordingly, the altered metabolic functions, including antigen synthesis, amino acids metabolism, short chain fatty acid production, and vitamin K synthesis of microbiota, were also corrected by FMT.<br><br>CONCLUSION: Fecal microbiota transplantation seems to be safe and effective for active UC patients who are nonresponsive to mesalazine or prednisone in the long-term. FMT could efficiently downregulate pro-inflammatory cytokines to ameliorate the inflammation.}, }
@article {pmid35444249, year = {2022}, author = {Soininen, L and Roslund, MI and Nurminen, N and Puhakka, R and Laitinen, OH and Hyöty, H and Sinkkonen, A and , }, title = {Indoor green wall affects health-associated commensal skin microbiota and enhances immune regulation: a randomized trial among urban office workers.}, journal = {Scientific reports}, volume = {12}, number = {1}, pages = {6518}, pmid = {35444249}, issn = {2045-2322}, mesh = {Bacteria ; Cytokines ; Humans ; Lactobacillus ; *Microbiota ; Skin ; }, abstract = {Urbanization reduces microbiological abundance and diversity, which has been associated with immune mediated diseases. Urban greening may be used as a prophylactic method to restore microbiological diversity in cities and among urbanites. This study evaluated the impact of air-circulating green walls on bacterial abundance and diversity on human skin, and on immune responses determined by blood cytokine measurements. Human subjects working in offices in two Finnish cities (Lahti and Tampere) participated in a two-week intervention, where green walls were installed in the rooms of the experimental group. Control group worked without green walls. Skin and blood samples were collected before (Day0), during (Day14) and two weeks after (Day28) the intervention. The relative abundance of genus Lactobacillus and the Shannon diversity of phylum Proteobacteria and class Gammaproteobacteria increased in the experimental group. Proteobacterial diversity was connected to the lower proinflammatory cytokine IL-17A level among participants in Lahti. In addition, the change in TGF-β1 levels was opposite between the experimental and control group. As skin Lactobacillus and the diversity of Proteobacteria and Gammaproteobacteria are considered advantageous for skin health, air-circulating green walls may induce beneficial changes in a human microbiome. The immunomodulatory potential of air-circulating green walls deserves further research attention.}, }
@article {pmid35441344, year = {2023}, author = {Roderburg, C and Loosen, SH and Joerdens, MS and Demir, M and Luedde, T and Kostev, K}, title = {Antibiotic therapy is associated with an increased incidence of cancer.}, journal = {Journal of cancer research and clinical oncology}, volume = {149}, number = {3}, pages = {1285-1293}, pmid = {35441344}, issn = {1432-1335}, mesh = {Humans ; Female ; Incidence ; Case-Control Studies ; Retrospective Studies ; Anti-Bacterial Agents/therapeutic use ; Penicillins ; Cephalosporins/therapeutic use ; *Breast Neoplasms/drug therapy ; *Hematologic Neoplasms/drug therapy ; }, abstract = {PURPOSE: There is a growing body of evidence suggesting the decisive involvement of the human microbiome in cancer development. The consumption of antibiotics may fundamentally change the microbiome and thereby create a precancerous environment promoting cancer development and growth. However, clinical data on the association between the consumption of antibiotics and cancer incidence have remained inconclusive. In this study, we quantified the association between the intake of different antibiotics and various cancer entities among outpatients from Germany.<br><br>METHODS: This retrospective case-control study based on the IQVIA Disease Analyzer database included 111,828 cancer patients and 111,828 non-cancer controls who were matched to cancer cases using propensity scores. Patients were categorized as non-users, low-consumption (up to 50th percentile), and high-consumption (above 50[th] percentile) users of antibiotics overall and for each antibiotic class. Multivariable logistic conditional regression models were used to study the association between antibiotic intake within 5&#xa0;years prior to the index date (first cancer diagnosis for cases or randomly selected date for controls) and cancer incidence.<br><br>RESULTS: The probability of cancer was significantly higher among patients with a history of antibiotic intake than in matched controls. Patients using penicillin or cephalosporins displayed a higher incidence of cancer, while the intake of tetracyclines and macrolides actually reduced the risk of cancer development slightly. A complex picture was observed in our cancer site-stratified analyses. Most notably, the consumption of penicillin was significantly and positively associated with cancer development in the respiratory organs only (low consumption OR: 1.33, 95% CI 1.20-1.47; high consumption OR 1.42, 95% CI 1.22-1.64) and cephalosporin consumption was significantly associated with respiratory organ cancer (low consumption OR: 1.32, 95% CI 1.17-1.48, high consumption OR: 1.47, 95% CI 1.29-1.66), breast cancer (high consumption OR: 1.40, 95% CI 1.25-1.56), and lymphoid and hematopoietic tissue cancer (high consumption OR: 1.50, 95% CI 1.35-1.66).<br><br>CONCLUSION: Our data strongly support the hypothesis that the intake of antibiotics is positively associated with the risk of cancer development.}, }
@article {pmid35440149, year = {2022}, author = {Maslennikov, R and Ivashkin, V and Ufimtseva, A and Poluektova, E and Ulyanin, A}, title = {Clostridioides difficile co-infection in patients with COVID-19.}, journal = {Future microbiology}, volume = {17}, number = {}, pages = {653-663}, pmid = {35440149}, issn = {1746-0921}, mesh = {Anti-Bacterial Agents/adverse effects ; *COVID-19/complications ; *Clostridioides difficile ; *Clostridium Infections/complications/diagnosis/epidemiology ; *Coinfection/drug therapy ; Diarrhea/drug therapy ; Humans ; Retrospective Studies ; }, abstract = {Aim: To assess the impact of Clostridioides difficile infection on the course of COVID-19. Methods: The authors included 809 patients with COVID-19 in this retrospective study: 55 had C. difficile infection, 23 had C. difficile-negative antibiotic-associated diarrhea and 731 had no diarrhea. C. difficile in feces was determined by immunochromatographic test for its toxins. Results:C. difficile infection was associated with increased risk of death (hazard ratio = 2.6; p = 0.021), especially after 20 days of disease (hazard ratio = 6.5; p < 0.001). C. difficile infection-associated diarrhea was longer and more severe than C. difficile-negative antibiotic-associated diarrhea. Unlike patients with C. difficile-negative antibiotic-associated diarrhea, patients with C. difficile infection were admitted to the intensive care unit and needed mechanical ventilation more often than those without diarrhea. Conclusion:C. difficile infection worsens the course and prognosis of COVID-19.}, }
@article {pmid35440042, year = {2022}, author = {Wolf, PG and Cowley, ES and Breister, A and Matatov, S and Lucio, L and Polak, P and Ridlon, JM and Gaskins, HR and Anantharaman, K}, title = {Diversity and distribution of sulfur metabolic genes in the human gut microbiome and their association with colorectal cancer.}, journal = {Microbiome}, volume = {10}, number = {1}, pages = {64}, pmid = {35440042}, issn = {2049-2618}, support = {T32 CA057699/CA/NCI NIH HHS/United States ; T15 LM007359/LM/NLM NIH HHS/United States ; R01 CA204808/CA/NCI NIH HHS/United States ; T32 GM008692/GM/NIGMS NIH HHS/United States ; T32 GM140935/GM/NIGMS NIH HHS/United States ; }, mesh = {Bacteria ; *Carcinoma ; *Colorectal Neoplasms/genetics ; *Gastrointestinal Microbiome/genetics ; Humans ; Sulfates/metabolism ; Sulfur/metabolism ; Taurine/metabolism ; }, abstract = {BACKGROUND: Recent evidence implicates microbial sulfidogenesis as a potential trigger of colorectal cancer (CRC), highlighting the need for comprehensive knowledge of sulfur metabolism within the human gut. Microbial sulfidogenesis produces genotoxic hydrogen sulfide (H2S) in the human colon using inorganic (sulfate) and organic (taurine/cysteine/methionine) substrates; however, the majority of studies have focused on sulfate reduction using dissimilatory sulfite reductases (Dsr).<br><br>RESULTS: Here, we show that genes for microbial sulfur metabolism are more abundant and diverse than previously observed and are statistically associated with CRC. Using ~ 17,000 bacterial genomes from publicly available stool metagenomes, we studied the diversity of sulfur metabolic genes in 667 participants across different health statuses: healthy, adenoma, and carcinoma. Sulfidogenic genes were harbored by 142 bacterial genera and both organic and inorganic sulfidogenic genes were associated with carcinoma. Significantly, the anaerobic sulfite reductase (asr) genes were twice as abundant as dsr, demonstrating that Asr is likely a more important contributor to sulfate reduction in the human gut than Dsr. We identified twelve potential pathways for reductive taurine metabolism and discovered novel genera harboring these pathways. Finally, the prevalence of metabolic genes for organic sulfur indicates that these understudied substrates may be the most abundant source of microbially derived H2S.<br><br>CONCLUSIONS: Our findings significantly expand knowledge of microbial sulfur metabolism in the human gut. We show that genes for microbial sulfur metabolism in the human gut are more prevalent than previously known, irrespective of health status (i.e., in both healthy and diseased states). Our results significantly increase the diversity of pathways and bacteria that are associated with microbial sulfur metabolism in the human gut. Overall, our results have implications for understanding the role of the human gut microbiome and its potential contributions to the pathogenesis of CRC. Video abstract.}, }
@article {pmid35432240, year = {2022}, author = {Si, J and Choi, Y and Raes, J and Ko, G and You, HJ}, title = {Sputum Bacterial Metacommunities in Distinguishing Heterogeneity in Respiratory Health and Disease.}, journal = {Frontiers in microbiology}, volume = {13}, number = {}, pages = {719541}, pmid = {35432240}, issn = {1664-302X}, abstract = {BACKGROUND AND OBJECTIVE: Cluster-based analysis, or community typing, has been attempted as a method for studying the human microbiome in various body niches with the aim of reducing variations in the bacterial composition and linking the defined communities to host health and disease. In this study, we have presented the bacterial subcommunities in the healthy and the diseased population cohorts and have assessed whether these subcommunities can distinguish different host health conditions.<br><br>METHODS: We performed community typing analysis on the sputum microbiome dataset obtained from a healthy Korean twin-family cohort (n = 202) and an external chronic obstructive pulmonary disease (COPD) cohort (n = 324) and implemented a networks analysis to investigate the associations of bacterial metacommunities with host health parameters and microbial interactions in disease.<br><br>RESULTS: The analysis of the sputum microbiome of a healthy Korean cohort revealed high levels of interindividual variation, which was driven by two dominant bacteria: Neisseria and Prevotella. Community typing of the cohort samples identified three metacommunities, namely, Neisseria 1 (N1), Neisseria 2 (N2), and Prevotella (P), each of which showed different functional potential and links to host traits (e.g., triglyceride levels, waist circumference, and levels of high-sensitivity C-reactive protein). In particular, the Prevotella-dominant metacommunity showed a low-community diversity, which implies an adverse health association. Network analysis of the healthy twin cohort illustrated co-occurrence of Prevotella with pathogenic anaerobic bacteria; this bacterial cluster was negatively associated with high-density lipoproteins but positively correlated with waist circumference, blood pressure, and pack-years. Community typing of the external COPD cohort identified three sub-metacommunities: one exclusively comprising healthy subjects (HSs) and the other two (CS1 and CS2) comprising patients. The two COPD metacommunities, CS1 and CS2, showed different abundances of specific pathogens, such as Serratia and Moraxella, as well as differing functional potential and community diversity. Network analysis of the COPD cohort showed enhanced bacterial coexclusions in the CS metacommunities when compared with HS metacommunity.<br><br>CONCLUSION: Overall, our findings point to a potential association between pulmonary Prevotella and host health and disease, making it possible to implement community typing for the diagnosis of heterogenic respiratory disease.}, }
@article {pmid35431497, year = {2022}, author = {Maslennikov, R and Ivashkin, V and Efremova, I and Poluektova, E and Kudryavtseva, A and Krasnov, G}, title = {Gut dysbiosis and small intestinal bacterial overgrowth as independent forms of gut microbiota disorders in cirrhosis.}, journal = {World journal of gastroenterology}, volume = {28}, number = {10}, pages = {1067-1077}, pmid = {35431497}, issn = {2219-2840}, mesh = {Bacteria/genetics ; Clostridiales ; Dysbiosis/microbiology ; Firmicutes/genetics ; *Gastrointestinal Microbiome ; Humans ; Liver Cirrhosis/diagnosis ; *Microbiota ; RNA, Ribosomal, 16S/genetics ; }, abstract = {BACKGROUND: Gut dysbiosis and small intestinal bacterial overgrowth (SIBO) are commonly observed in patients with cirrhosis. Despite the substantial number of articles describing the relations between disorders of gut microbiota and various manifestations of cirrhosis, dysbiosis and SIBO were always studied separately.<br><br>AIM: To study the relationship of gut dysbiosis and SIBO in cirrhosis.<br><br>METHODS: This observational study included 47 in-patients with cirrhosis. Stool microbiome was assessed using 16S rRNA gene sequencing. SIBO was assessed using the lactulose hydrogen breath test.<br><br>RESULTS: SIBO was found in 24/47 (51.1%) patients. Patients with SIBO had a higher abundance of Firmicutes (P = 0.017) and Fusobacteria (P = 0.011), and a lower abundance of Bacteroidetes (P = 0.013) than patients without SIBO. This increase in the abundance of Firmicutes occurred mainly due to an increase in the abundance of bacteria from the genus Blautia (P = 0.020) of the Lachnospiraceae family (P = 0.047), while the abundance of other major families of this phylum [Ruminococcaceae (P = 0.856), Peptostreptococcaceae (P = 0.066), Clostridiaceae (P = 0.463), Eubacteriaceae (P = 0.463), Lactobacillaceae (P = 0.413), and Veillonellaceae (P = 0.632)] did not differ significantly between the patients with and without SIBO. Reduced level of Bacteroidetes in samples from patients with SIBO was a result of the decrease in bacterial numbers from all the major families of this phylum [Bacteroidaceae (P = 0.014), Porphyromonadaceae (P = 0.002), and Rikenellaceae (P = 0.047)], with the exception of Prevotellaceae (P = 0.941). There were no significant differences in the abundance of taxa that were the main biomarkers of cirrhosis-associated gut dysbiosis [Proteobacteria (P = 0.790), Bacilli (P = 0.573), Enterobacteriaceae (P = 0.632), Streptococcaceae (P = 0.170), Staphylococcaceae (P = 0.450), and Enterococcaceae (P = 0.873)] between patients with and without SIBO.<br><br>CONCLUSION: Despite the differences observed in the gut microbiome between patients with and without SIBO, gut dysbiosis and SIBO are most likely independent disorders of gut microbiota in cirrhosis.}, }
@article {pmid35429105, year = {2022}, author = {Li, D and Van De Werfhorst, LC and Holden, PA}, title = {Genetic sequence data evidence that human faecal-associated HF183 sequences are on human skin and in urine.}, journal = {Journal of applied microbiology}, volume = {133}, number = {2}, pages = {232-240}, pmid = {35429105}, issn = {1365-2672}, support = {//Mr. Henry (Sam) Wheeler/ ; Proposition 84//the State of California Clean Beach Initiative/ ; }, mesh = {Environmental Monitoring/methods ; Feces ; Genetic Markers ; Humans ; Polymerase Chain Reaction/methods ; RNA, Ribosomal, 16S/genetics ; *Sewage ; *Water Microbiology ; }, abstract = {AIMS: The DNA marker HF183 is a partial 16S rRNA gene sequence highly specific to human-associated Bacteroides including Bacteroides dorei. While HF183 is used to assess human faecal contamination in aquatic environments worldwide, little is known about the existence of HF183 and B. dorei in human microbiomes outside of the human gastrointestinal tract and faeces.<br><br>METHODS AND RESULTS: Previously published human skin and urine microbiome data sets from five independent human body skin studies, the Human Microbiome Project (HMP) and three independent human urine studies were analysed. The HF183 gene sequence was detected in all skin data sets, with the ratios of positive samples ranging from 0.5% to 36.3%. Popliteal fossa (knee), volar forearm and inguinal (groin) creases were identified as hot spots. HF183 was detected in two of three urine data sets, with ratios of positive samples ranging from 0% to 37.5%. All HF183-containing sequences from these data sets were classified as associated with B. dorei.<br><br>CONCLUSIONS: HF183 is widespread on human skin and present in urine.<br><br>Skin and urine microbiomes could be sources of HF183 to environmental waters. Such non-faecal sources of HF183 might explain low concentrations of HF183 in recreational waters when swimmers are present.}, }
@article {pmid35427870, year = {2022}, author = {Mohammadzadeh, R and Mahnert, A and Duller, S and Moissl-Eichinger, C}, title = {Archaeal key-residents within the human microbiome: characteristics, interactions and involvement in health and disease.}, journal = {Current opinion in microbiology}, volume = {67}, number = {}, pages = {102146}, doi = {10.1016/j.mib.2022.102146}, pmid = {35427870}, issn = {1879-0364}, support = {P 30796/FWF_/Austrian Science Fund FWF/Austria ; P 32697/FWF_/Austrian Science Fund FWF/Austria ; }, mesh = {*Archaea/genetics ; Eukaryota ; Eukaryotic Cells ; Humans ; *Microbiota ; Phylogeny ; }, abstract = {Since the introduction of Archaea as new domain of life more than 40 years ago, they are no longer regarded as eccentric inhabitants of extreme ecosystems. These microorganisms are widespread in various moderate ecosystems, including eukaryotic hosts such as humans. Indeed, members of the archaeal community are now recognized as paramount constituents of human microbiome, while their definite role in disease or health is not fully elucidated and no archaeal pathogen has been reported. Here, we present a brief overview of archaea residing in and on the human body, with a specific focus on common lineages including Methanobrevibacter, Methanosphaeraand Methanomassilococcales.}, }
@article {pmid35421683, year = {2022}, author = {Safari, Z and Sadeghizadeh, M and Asgaritarghi, G and Bardania, H and Sadeghizadeh, D and Soudi, S}, title = {M13 phage coated surface elicits an anti-inflammatory response in BALB/c and C57BL/6 peritoneal macrophages.}, journal = {International immunopharmacology}, volume = {107}, number = {}, pages = {108654}, doi = {10.1016/j.intimp.2022.108654}, pmid = {35421683}, issn = {1878-1705}, mesh = {Animals ; Anti-Inflammatory Agents/metabolism ; Arginine ; *Bacteriophage M13/metabolism ; Cytokines/metabolism ; *Macrophages, Peritoneal ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Nitric Oxide/metabolism ; }, abstract = {Bacteriophages are one of the viral components of the human microbiome. M13 phages have recently been considered for immunotherapy because they can be detected by immune cells and stimulated immune responses. Macrophages are essential innate immune cells that respond to stimuli and direct subsequent immune responses. Therefore, it is crucial to evaluate the immunomodulatory effect of phage on macrophage function. For this purpose, peritoneal macrophages from BALB/c and C57BL/6 mice were cultured on the M13 phage, M13 phage-RGD, gelatin-coated, and un-coated wells. Then macrophages were examined for morphological characteristics, L. arginine metabolism, redox potential, inflammatory cytokine production, and phagocytic activity after two and seven days of culture. We observed that M13 phage-coated surfaces induced anti-inflammatory cytokines production and reduced inflammatory cytokines level of BALB/c and C57BL/6 macrophages at the steady-state and post LPS stimulation. In addition, L. arginine metabolism and phagocytic activity of macrophages were directed to the M2 phenotype by induction of arginase-1 and efferocytosis in the M13 phage-containing groups, respectively. The present study confirms the M13 phage's ability to polarize macrophages toward the M2 phenotype. However, using M13 phage in treating inflammatory diseases in animal models could determine their immunotherapy capacity in the future.}, }
@article {pmid35421341, year = {2022}, author = {Kostic, AD}, title = {The human microbiome: A coming of age story.}, journal = {Cell host &amp; microbe}, volume = {30}, number = {4}, pages = {449-453}, doi = {10.1016/j.chom.2022.03.020}, pmid = {35421341}, issn = {1934-6069}, mesh = {Humans ; *Microbiota ; Research Personnel ; }, abstract = {The human microbiome field is coming of age, but it is still defining itself. I can say the same as an investigator who started his career in the early days of this expanding field. This commentary reflects on my Cell Host &amp; Microbe papers along this journey that captured the field's progress.}, }
@article {pmid35416697, year = {2022}, author = {Higashi, DL and McGuire, S and Abdelrahman, YM and Zou, Z and Qin, H and Anderson, D and Palmer, EA and Kreth, J and Merritt, J}, title = {Development of the First Tractable Genetic System for Parvimonas micra, a Ubiquitous Pathobiont in Human Dysbiotic Disease.}, journal = {Microbiology spectrum}, volume = {10}, number = {2}, pages = {e0046522}, pmid = {35416697}, issn = {2165-0497}, support = {R01 DE029492/DE/NIDCR NIH HHS/United States ; R21 DE029612/DE/NIDCR NIH HHS/United States ; R35 DE028252/DE/NIDCR NIH HHS/United States ; }, mesh = {Carcinogenesis ; *Firmicutes/genetics ; *Gram-Positive Bacteria ; Humans ; }, abstract = {Parvimonas micra is a Gram-positive obligate anaerobe and a typical member of the human microbiome. P. micra is among the most highly enriched species at numerous sites of mucosal dysbiotic disease and is closely associated with the development of multiple types of malignant tumors. Despite its strong association with disease, surprisingly little is known about P. micra pathobiology, which is directly attributable to its longstanding genetic intractability. To address this problem, we directly isolated a collection of P. micra strains from odontogenic abscess clinical specimens and then screened these isolates for natural competence. Amazingly, all of the P. micra clinical isolates exhibited various levels of natural competence, including the reference strain ATCC 33270. By exploiting this ability, we were able to employ cloning-independent methodologies to engineer and complement a variety of targeted chromosomal genetic mutations directly within low-passage-number clinical isolates. To develop a tractable genetic system for P. micra, we first adapted renilla-based bioluminescence for highly sensitive reporter studies. This reporter system was then applied for the development of the novel Theo+ theophylline-inducible riboswitch for tunable gene expression studies over a broad dynamic range. Finally, we demonstrate the feasibility of generating mariner-based transposon sequencing (Tn-seq) libraries for forward genetic screening in P. micra. With the availability of a highly efficient transformation protocol and the current suite of genetic tools, P. micra should now be considered a fully genetically tractable organism suitable for molecular genetic research. The methods presented here provide a clear path to investigate the understudied role of P. micra in polymicrobial infections and tumorigenesis. IMPORTANCE Parvimonas micra is among the most highly enriched species at numerous sites of mucosal dysbiotic disease and is closely associated with numerous cancers. Despite this, little is known about P. micra pathobiology, which is directly attributable to its longstanding genetic intractability. In this study, we provide the first report of P. micra natural competence and describe the only tractable genetic system for this species. The methods presented here will allow for the detailed study of P. micra and its role in infection and tumorigenesis.}, }
@article {pmid35410573, year = {2022}, author = {Walles, M and Pähler, A and Isin, EM and Weidolf, L}, title = {Meeting report of the second European biotransformation workshop.}, journal = {Xenobiotica; the fate of foreign compounds in biological systems}, volume = {52}, number = {4}, pages = {426-431}, doi = {10.1080/00498254.2022.2064253}, pmid = {35410573}, issn = {1366-5928}, mesh = {Biotransformation ; Humans ; *Immunoconjugates ; Peptides ; }, abstract = {Challenges and opportunities in the field of biotransformation were presented and discussed at the 2nd European Biotransformation workshop which was conducted virtually in collaboration with the DMDG on November 24/25, 2021. Here we summarise the presentations and discussions from this workshop.The following topics were covered:Regulatory requirements and biotransformation studies for antibody drug conjugates (ADCs) and antisense oligonucleotides (ASOs).Solutions for mass spectral data processing of peptides and oligonucleotides.Future outsourcing needs in biotransformation for new modalities.Established quantitative and qualitative workflows for metabolite identification.New in vitro systems to study new chemical entities (NCEs) with low metabolic turnover.New strategies on the timing of the human ADME (absorption, distribution, metabolism, excretion) study and to investigate the impact of human microbiome on drug development.}, }
@article {pmid35410233, year = {2022}, author = {Ghaffari, P and Shoaie, S and Nielsen, LK}, title = {Irritable bowel syndrome and microbiome; Switching from conventional diagnosis and therapies to personalized interventions.}, journal = {Journal of translational medicine}, volume = {20}, number = {1}, pages = {173}, pmid = {35410233}, issn = {1479-5876}, support = {BB/S016899/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {*Gastrointestinal Microbiome ; Humans ; *Irritable Bowel Syndrome/diagnosis/therapy ; *Microbiota ; }, abstract = {The human microbiome has been linked to several diseases. Gastrointestinal diseases are still one of the most prominent area of study in host-microbiome interactions however the underlying microbial mechanisms in these disorders are not fully established. Irritable bowel syndrome (IBS) remains as one of the prominent disorders with significant changes in the gut microbiome composition and without definitive treatment. IBS has a severe impact on socio-economic and patient's lifestyle. The association studies between the IBS and microbiome have shed a light on relevance of microbial composition, and hence microbiome-based trials were designed. However, there are no clear evidence of potential treatment for IBS. This review summarizes the epidemiology and socioeconomic impact of IBS and then focus on microbiome observational and clinical trials. At the end, we propose a new perspective on using data-driven approach and applying computational modelling and machine learning to design microbiome-aware personalized treatment for IBS.}, }
@article {pmid35406091, year = {2022}, author = {Verstraeten, S and Sencio, V and Raise, A and Huillet, E and Layec, S and Deruyter, L and Heumel, S and Auger, S and Robert, V and Langella, P and Beney, L and Trottein, F and Thomas, M}, title = {Description of a Newly Isolated Blautia faecis Strain and Its Benefit in Mouse Models of Post-Influenza Secondary Enteric and Pulmonary Infections.}, journal = {Nutrients}, volume = {14}, number = {7}, pages = {}, pmid = {35406091}, issn = {2072-6643}, support = {ANR-16-CE29-0020 and ANR-17-CE15-0020-01//Agence Nationale de la Recherche/ ; }, mesh = {Animals ; *Clostridiales/classification/isolation &amp; purification ; Disease Models, Animal ; Humans ; Influenza, Human/complications ; Interleukin-8 ; Mice ; *Orthomyxoviridae Infections/complications ; *Pneumococcal Infections/microbiology/prevention &amp; control ; *Salmonella Infections, Animal/microbiology/prevention &amp; control ; Salmonella typhimurium ; Streptococcus pneumoniae ; }, abstract = {The expanding knowledge on the systemic influence of the human microbiome suggests that fecal samples are underexploited sources of new beneficial strains for extra-intestinal health. We have recently shown that acetate, a main circulating microbiota-derived molecule, reduces the deleterious effects of pulmonary Streptococcus pneumoniae and enteric Salmonella enterica serovar Typhimurium bacterial post-influenza superinfections. Considering the beneficial and broad effects of acetate, we intended to isolate a commensal strain, producing acetate and potentially exploitable in the context of respiratory infections. We designed successive steps to select intestinal commensals that are extremely oxygen-sensitive, cultivable after a freezing process, without a proinflammatory effect on IL-8 induction, and producing acetate. We have identified the Blautia faecis DSM33383 strain, which decreased the TNFα-induced production of IL-8 by the intestinal epithelial cell line HT-29. The beneficial effect of this bacterial strain was further studied in two preclinical models of post-influenza Streptococcus pneumoniae (S.p) and Salmonella enterica serovar Typhimurium (S.t) superinfection. The intragastrical administration of Blautia faecis DSM33383 led to protection in influenza-infected mice suffering from an S.p. and, to a lesser extent, from an S.t secondary infection. Altogether, this study showed that Blautia faecis DSM33383 could be a promising candidate for preventive management of respiratory infectious diseases.}, }
@article {pmid35399743, year = {2021}, author = {Hayes, CV and Eley, CV and Wood, F and Demirjian, A and McNulty, CAM}, title = {Knowledge and attitudes of adolescents towards the human microbiome and antibiotic resistance: a qualitative study.}, journal = {JAC-antimicrobial resistance}, volume = {3}, number = {2}, pages = {dlab039}, pmid = {35399743}, issn = {2632-1823}, abstract = {BACKGROUND: Antibiotic and dietary behaviour affect the human microbiome and influence antibiotic resistance development. Adolescents are a key demographic for influencing knowledge and behaviour change.<br><br>OBJECTIVES: To explore adolescents' knowledge and attitudes towards the microbiome and antibiotic resistance, and the capability, motivation and opportunity for educators to integrate microbiome teaching in schools.<br><br>METHODS: Qualitative study informed by the Theoretical Domains Framework (TDF) and COM-B model. Six educational establishments were purposively selected by rural/city and socioeconomic status, within Gloucestershire, South West England in 2019. Forty 14-18-year olds participated in focus groups, and eight science or health educators participated in interviews. Data were analysed thematically, double-coded and mapped to the TDF/COM-B.<br><br>RESULTS: Adolescents were aware of 'good microbes' in the body but lacked deeper knowledge. Adolescents' knowledge of, and intentions to use, antibiotics appropriately differed by their levels of scientific study. Adolescents lacked knowledge on the consequences of diet on the microbiome, and therefore lacked capability and motivation to change behaviour. Educators felt capable and motivated to teach microbiome topics but lacked opportunity though absence of topics in the national curriculum and lack of time to teach additional topics.<br><br>CONCLUSIONS: A disparity in knowledge of adolescents needs to be addressed through increasing antibiotic and microbiome topics in the national curriculum. Public antibiotic campaigns could include communication about the microbiome to increase awareness. Educational resources could motivate adolescents and improve their knowledge, skills and opportunity to improve diet and antibiotic use; so, supporting the UK antimicrobial resistance (AMR) national action plan.}, }
@article {pmid35399529, year = {2022}, author = {van Dijk, MC and de Kruijff, RM and Hagedoorn, PL}, title = {The Role of Iron in Staphylococcus aureus Infection and Human Disease: A Metal Tug of War at the Host-Microbe Interface.}, journal = {Frontiers in cell and developmental biology}, volume = {10}, number = {}, pages = {857237}, pmid = {35399529}, issn = {2296-634X}, abstract = {Iron deficiency anemia can be treated with oral or intravenous Fe supplementation. Such supplementation has considerable effects on the human microbiome, and on opportunistic pathogenic micro-organisms. Molecular understanding of the control and regulation of Fe availability at the host-microbe interface is crucial to interpreting the side effects of Fe supplementation. Here, we provide a concise overview of the regulation of Fe by the opportunistic pathogen Staphylococcus aureus. Ferric uptake regulator (Fur) plays a central role in controlling Fe uptake, utilization and storage in order to maintain a required value. The micro-organism has a strong preference for heme iron as an Fe source, which is enabled by the Iron-regulated surface determinant (Isd) system. The strategies it employs to overcome Fe restriction imposed by the host include: hijacking host proteins, replacing metal cofactors, and replacing functions by non-metal dependent enzymes. We propose that integrated omics approaches, which include metalloproteomics, are necessary to provide a comprehensive understanding of the metal tug of war at the host-microbe interface down to the molecular level.}, }
@article {pmid35399144, year = {2022}, author = {Badawy, S and Baka, ZAM and Abou-Dobara, MI and El-Sayed, AKA and Skurnik, M}, title = {Biological and molecular characterization of fEg-Eco19, a lytic bacteriophage active against an antibiotic-resistant clinical Escherichia coli isolate.}, journal = {Archives of virology}, volume = {167}, number = {5}, pages = {1333-1341}, pmid = {35399144}, issn = {1432-8798}, support = {288701//Academy of Finland/ ; 2016//Jane ja Aatos Erkon S&#xe4;&#xe4;ti&#xf6;/ ; }, mesh = {Anti-Bacterial Agents/pharmacology ; *Bacteriophages/genetics ; *Caudovirales/genetics ; Escherichia coli/genetics ; Genome, Viral ; Host Specificity ; }, abstract = {Characterization of bacteriophages facilitates better understanding of their biology, host specificity, genomic diversity, and adaptation to their bacterial hosts. This, in turn, is important for the exploitation of phages for therapeutic purposes, as the use of uncharacterized phages may lead to treatment failure. The present study describes the isolation and characterization of a bacteriophage effective against the important clinical pathogen Escherichia coli, which shows increasing accumulation of antibiotic resistance. Phage fEg-Eco19, which is specific for a clinical E. coli strain, was isolated from an Egyptian sewage sample. Phage fEg-Eco19 formed clear, sharp-edged, round plaques. Electron microscopy showed that the isolated phage is tailed and therefore belongs to the order Caudovirales, and morphologically, it resembles siphoviruses. The diameter of the icosahedral head of fEg-Eco19 is 68 ± 2 nm, and the non-contractile tail length and diameter are 118 ± 0.2 and 13 ± 0.6 nm, respectively. The host range of the phage was found to be narrow, as it infected only two out of 137 clinical E. coli strains tested. The phage genome is 45,805 bp in length with a GC content of 50.3% and contains 76 predicted genes. Comparison of predicted and experimental restriction digestion patterns allowed rough mapping of the physical ends of the phage genome, which was confirmed using the PhageTerm tool. Annotation of the predicted genes revealed gene products belonging to several functional groups, including regulatory proteins, DNA packaging and phage structural proteins, host lysis proteins, and proteins involved in DNA/RNA metabolism and replication.}, }
@article {pmid35395818, year = {2022}, author = {Shetty, SA and Kuipers, B and Atashgahi, S and Aalvink, S and Smidt, H and de Vos, WM}, title = {Inter-species Metabolic Interactions in an In-vitro Minimal Human Gut Microbiome of Core Bacteria.}, journal = {NPJ biofilms and microbiomes}, volume = {8}, number = {1}, pages = {21}, pmid = {35395818}, issn = {2055-5008}, mesh = {Bacteria/genetics/metabolism ; Colon/microbiology ; Dietary Fiber ; Fatty Acids, Volatile ; *Gastrointestinal Microbiome ; Humans ; }, abstract = {Knowledge of the functional roles and interspecies interactions are crucial for improving our understanding of the human intestinal microbiome in health and disease. However, the complexity of the human intestinal microbiome and technical challenges in investigating it pose major challenges. In this proof-of-concept study, we rationally designed, assembled and experimentally tested a synthetic Diet-based Minimal Microbiome (Db-MM) consisting of ten core intestinal bacterial species that together are capable of efficiently converting dietary fibres into short chain fatty acids (SCFAs). Despite their genomic potential for metabolic competition, all ten bacteria coexisted during growth on a mixture of dietary fibres, including pectin, inulin, xylan, cellobiose and starch. By integrated analyses of metabolite production, community composition and metatranscriptomics-based gene expression data, we identified interspecies metabolic interactions leading to production of key SCFAs such as butyrate and propionate. While public goods, such as sugars liberated from colonic fibres, are harvested by non-degraders, some species thrive by cross-feeding on energetically challenging substrates, including the butyrogenic conversion of acetate and lactate. Using a reductionist approach in an in-vitro system combined with functional measurements, our study provides key insights into the complex interspecies metabolic interactions between core intestinal bacterial species.}, }
@article {pmid35393656, year = {2022}, author = {Manos, J}, title = {The human microbiome in disease and pathology.}, journal = {APMIS : acta pathologica, microbiologica, et immunologica Scandinavica}, volume = {130}, number = {12}, pages = {690-705}, pmid = {35393656}, issn = {1600-0463}, mesh = {Humans ; Adult ; Dysbiosis/microbiology ; *Diabetes Mellitus, Type 2 ; *Microbiota ; *Gastrointestinal Microbiome ; Bacteria ; }, abstract = {This narrative review seeks to examine the relationships between bacterial microbiomes and infectious disease. This is achieved by detailing how different human host microbiomes develop and function, from the earliest infant acquisitions of maternal and environmental species through to the full development of microbiomes by adulthood. Communication between bacterial species or communities of species within and outside of the microbiome is a factor in both maintenance of homeostasis and management of threats from the external environment. Dysbiosis of this homeostasis is key to understanding the development of disease states. Several microbiomes and the microbiota within are used as prime examples of how changes in species composition, particularly at the phylum level, leads to such diverse conditions as inflammatory bowel disease (IBD), type 2 diabetes, psoriasis, Parkinson's disease, reflux oesophagitis and others. The review examines spatial relationships between microbiomes to understand how dysbiosis in the gut microbiome in particular can influence diseases in distant host sites via routes such as the gut-lung, gut-skin and gut-brain axes. Microbiome interaction with host processes such as adaptive immunity is increasingly identified as critical to developing the capacity of the immune system to react to pathogens. Dysbiosis of essential bacteria involved in modification of host substrates such as bile acid components can result in development of Crohn's disease, small intestine bacterial overgrowth, hepatic cancer and obesity. Interactions between microbiomes in distantly located sites are being increasingly being identified, resulting in a 'whole of body' effect by the combined host microbiome.}, }
@article {pmid35392614, year = {2022}, author = {Du, Y and Feng, R and Chang, ET and Debelius, JW and Yin, L and Xu, M and Huang, T and Zhou, X and Xiao, X and Li, Y and Liao, J and Zheng, Y and Huang, G and Adami, HO and Zhang, Z and Cai, Y and Ye, W}, title = {Influence of Pre-treatment Saliva Microbial Diversity and Composition on Nasopharyngeal Carcinoma Prognosis.}, journal = {Frontiers in cellular and infection microbiology}, volume = {12}, number = {}, pages = {831409}, pmid = {35392614}, issn = {2235-2988}, mesh = {Humans ; Nasopharyngeal Carcinoma ; *Nasopharyngeal Neoplasms/microbiology ; Phylogeny ; RNA, Ribosomal, 16S/genetics ; *Saliva/microbiology ; }, abstract = {BACKGROUND: The human microbiome has been reported to mediate the response to anticancer therapies. However, research about the influence of the oral microbiome on nasopharyngeal carcinoma (NPC) survival is lacking. We aimed to explore the effect of oral microbiota on NPC prognosis.<br><br>METHODS: Four hundred eighty-two population-based NPC cases in southern China between 2010 and 2013 were followed for survival, and their saliva samples were profiled using 16s rRNA sequencing. We analyzed associations of the oral microbiome diversity with mortality from all causes and NPC.<br><br>RESULTS: Within- and between-community diversities of saliva were associated with mortality with an average of 5.29 years follow-up. Lower Faith's phylogenetic diversity was related to higher all-cause mortality [adjusted hazard ratio (aHR), 1.52 (95% confidence interval (CI), 1.06-2.17)] and NPC-specific mortality [aHR, 1.57 (95% CI, 1.07-2.29)], compared with medium diversity, but higher phylogenetic diversity was not protective. The third principal coordinate (PC3) identified from principal coordinates analysis (PCoA) on Bray-Curtis distance was marginally associated with reduced all-cause mortality [aHR, 0.85 (95% CI, 0.73-1.00)], as was the first principal coordinate (PC1) from PCoA on weighted UniFrac [aHR, 0.86 (95% CI, 0.74-1.00)], but neither was associated with NPC-specific mortality. PC3 from robust principal components analysis was associated with lower all-cause and NPC-specific mortalities, with HRs of 0.72 (95% CI, 0.61-0.85) and 0.71 (95% CI, 0.60-0.85), respectively.<br><br>CONCLUSIONS: Oral microbiome may be an explanatory factor for NPC prognosis. Lower within-community diversity was associated with higher mortality, and certain measures of between-community diversity were related to mortality. Specifically, candidate bacteria were not related to mortality, suggesting that observed associations may be due to global patterns rather than particular pathogens.}, }
@article {pmid35392604, year = {2022}, author = {Glazier, VE}, title = {EFG1, Everyone's Favorite Gene in Candida albicans: A Comprehensive Literature Review.}, journal = {Frontiers in cellular and infection microbiology}, volume = {12}, number = {}, pages = {855229}, pmid = {35392604}, issn = {2235-2988}, mesh = {*Candida albicans ; *DNA-Binding Proteins/genetics/metabolism ; *Fungal Proteins/genetics/metabolism ; Gene Expression Regulation, Fungal ; Humans ; Hyphae ; *Transcription Factors/genetics/metabolism ; }, abstract = {Candida sp. are among the most common fungal commensals found in the human microbiome. Although Candida can be found residing harmlessly on the surface of the skin and mucosal membranes, these opportunistic fungi have the potential to cause superficial skin, nail, and mucus membrane infections as well as life threatening systemic infections. Severity of infection is dependent on both fungal and host factors including the immune status of the host. Virulence factors associated with Candida sp. pathogenicity include adhesin proteins, degradative enzymes, phenotypic switching, and morphogenesis. A central transcriptional regulator of morphogenesis, the transcription factor Efg1 was first characterized in Candida albicans in 1997. Since then, EFG1 has been referenced in the Candida literature over three thousand times, with the number of citations growing daily. Arguably one of the most well studied genes in Candida albicans, EFG1 has been referenced in nearly all contexts of Candida biology from the development of novel therapeutics to white opaque switching, hyphae morphology to immunology. In the review that follows we will synthesize the research that has been performed on this extensively studied transcription factor and highlight several important unanswered questions.}, }
@article {pmid35388189, year = {2022}, author = {Aggarwala, V and Mogno, I and Li, Z and Yang, C and Britton, GJ and Chen-Liaw, A and Mitcham, J and Bongers, G and Gevers, D and Clemente, JC and Colombel, JF and Grinspan, A and Faith, J}, title = {Author Correction: Precise quantification of bacterial strains after fecal microbiota transplantation delineates long-term engraftment and explains outcomes.}, journal = {Nature microbiology}, volume = {7}, number = {5}, pages = {736}, doi = {10.1038/s41564-022-01118-8}, pmid = {35388189}, issn = {2058-5276}, support = {650451//Crohn's and Colitis Foundation (Crohn's &amp; Colitis Foundation)/ ; 580924//Crohn's and Colitis Foundation (Crohn's &amp; Colitis Foundation)/ ; }, }
@article {pmid35382166, year = {2022}, author = {Yadav, M and Chauhan, NS}, title = {Microbiome therapeutics: exploring the present scenario and challenges.}, journal = {Gastroenterology report}, volume = {10}, number = {}, pages = {goab046}, pmid = {35382166}, issn = {2052-0034}, abstract = {Human gut-microbiome explorations have enriched our understanding of microbial colonization, maturation, and dysbiosis in health-and-disease subsets. The enormous metabolic potential of gut microbes and their role in the maintenance of human health is emerging, with new avenues to use them as therapeutic agents to overcome human disorders. Microbiome therapeutics are aimed at engineering the gut microbiome using additive, subtractive, or modulatory therapy with an application of native or engineered microbes, antibiotics, bacteriophages, and bacteriocins. This approach could overcome the limitation of conventional therapeutics by providing personalized, harmonized, reliable, and sustainable treatment. Its huge economic potential has been shown in the global therapeutics market. Despite the therapeutic and economical potential, microbiome therapeutics is still in the developing stage and is facing various technical and administrative issues that require research attention. This review aims to address the current knowledge and landscape of microbiome therapeutics, provides an overview of existing health-and-disease applications, and discusses the potential future directions of microbiome modulations.}, }
@article {pmid35380149, year = {2022}, author = {Kynkäänniemi, E and Lahtinen, MH and Jian, C and Salonen, A and Hatanpää, T and Mikkonen, KS and Pajari, AM}, title = {Correction: Gut microbiota can utilize prebiotic birch glucuronoxylan in production of short-chain fatty acids in rats.}, journal = {Food &amp; function}, volume = {13}, number = {8}, pages = {4770}, doi = {10.1039/d2fo90028a}, pmid = {35380149}, issn = {2042-650X}, abstract = {Correction for 'Gut microbiota can utilize prebiotic birch glucuronoxylan in production of short-chain fatty acids in rats' by Emma Kynkäänniemi et al., Food Funct., 2022, 13, 3746-3759, DOI: 10.1039/D1FO03922A.}, }
@article {pmid35371778, year = {2022}, author = {Segal, E and Bar Yosef, S and Axel, A and Keller, N and Shlaeffer, F and Amir, A and Efroni, G and Haberman, Y}, title = {Outbreak of Sepsis Following Surgery: Utilizing 16S RNA Sequencing To Detect the Source of Infection.}, journal = {Cureus}, volume = {14}, number = {2}, pages = {e22487}, pmid = {35371778}, issn = {2168-8184}, abstract = {Background Nosocomial infections are a significant health concern. Following surgery, infections are most commonly associated with the surgical site, yet there are other potential sources for infections after surgical interventions. Identification of the source of infections can be very challenging. Methodology An outbreak of postoperative infections following surgery led to intensive care unit (ICU) admission of patients immediately after the surgical procedure. The blood cultures of two patients were positive for Citrobacter freundii. The only connection between all cases was the anesthesiologist. An epidemiological inquiry could not definitively identify the source of the outbreak. Therefore, we utilized an RNA sequencing technique to evaluate the microbiome of the anesthesiologist and compared the results to bacteria cultured from the bloodstream of the two patients. Results The anesthesiologist's microbiome contained amplicons that were identical to those of the bacteria in the patient's bloodstream. Because Citrobacter freundii is an uncommon source of bloodstream infections, and in the normal human microbiome, the results establish the source of a cluster of infections to the anesthesiologist. Conclusions In cases of nosocomial infections, when conventional microbiological techniques do not clearly establish the source of the infection, using 16S RNA sequencing should be considered.}, }
@article {pmid35369727, year = {2022}, author = {Zhu, Q and Huang, S and Gonzalez, A and McGrath, I and McDonald, D and Haiminen, N and Armstrong, G and Vázquez-Baeza, Y and Yu, J and Kuczynski, J and Sepich-Poore, GD and Swafford, AD and Das, P and Shaffer, JP and Lejzerowicz, F and Belda-Ferre, P and Havulinna, AS and Méric, G and Niiranen, T and Lahti, L and Salomaa, V and Kim, HC and Jain, M and Inouye, M and Gilbert, JA and Knight, R}, title = {Phylogeny-Aware Analysis of Metagenome Community Ecology Based on Matched Reference Genomes while Bypassing Taxonomy.}, journal = {mSystems}, volume = {7}, number = {2}, pages = {e0016722}, pmid = {35369727}, issn = {2379-5077}, support = {RG/13/13/30194/BHF_/British Heart Foundation/United Kingdom ; DP1 AT010885/AT/NCCIH NIH HHS/United States ; U24 CA248454/CA/NCI NIH HHS/United States ; RG/18/13/33946/BHF_/British Heart Foundation/United Kingdom ; CH/12/2/29428/BHF_/British Heart Foundation/United Kingdom ; K12 GM068524/GM/NIGMS NIH HHS/United States ; F30 CA243480/CA/NCI NIH HHS/United States ; U19 AG063744/AG/NIA NIH HHS/United States ; P30 DK120515/DK/NIDDK NIH HHS/United States ; }, mesh = {Humans ; Phylogeny ; *Metagenome ; RNA, Ribosomal, 16S/genetics ; *Microbiota ; Ecology ; }, abstract = {We introduce the operational genomic unit (OGU) method, a metagenome analysis strategy that directly exploits sequence alignment hits to individual reference genomes as the minimum unit for assessing the diversity of microbial communities and their relevance to environmental factors. This approach is independent of taxonomic classification, granting the possibility of maximal resolution of community composition, and organizes features into an accurate hierarchy using a phylogenomic tree. The outputs are suitable for contemporary analytical protocols for community ecology, differential abundance, and supervised learning while supporting phylogenetic methods, such as UniFrac and phylofactorization, that are seldom applied to shotgun metagenomics despite being prevalent in 16S rRNA gene amplicon studies. As demonstrated in two real-world case studies, the OGU method produces biologically meaningful patterns from microbiome data sets. Such patterns further remain detectable at very low metagenomic sequencing depths. Compared with taxonomic unit-based analyses implemented in currently adopted metagenomics tools, and the analysis of 16S rRNA gene amplicon sequence variants, this method shows superiority in informing biologically relevant insights, including stronger correlation with body environment and host sex on the Human Microbiome Project data set and more accurate prediction of human age by the gut microbiomes of Finnish individuals included in the FINRISK 2002 cohort. We provide Woltka, a bioinformatics tool to implement this method, with full integration with the QIIME 2 package and the Qiita web platform, to facilitate adoption of the OGU method in future metagenomics studies. IMPORTANCE Shotgun metagenomics is a powerful, yet computationally challenging, technique compared to 16S rRNA gene amplicon sequencing for decoding the composition and structure of microbial communities. Current analyses of metagenomic data are primarily based on taxonomic classification, which is limited in feature resolution. To solve these challenges, we introduce operational genomic units (OGUs), which are the individual reference genomes derived from sequence alignment results, without further assigning them taxonomy. The OGU method advances current read-based metagenomics in two dimensions: (i) providing maximal resolution of community composition and (ii) permitting use of phylogeny-aware tools. Our analysis of real-world data sets shows that it is advantageous over currently adopted metagenomic analysis methods and the finest-grained 16S rRNA analysis methods in predicting biological traits. We thus propose the adoption of OGUs as an effective practice in metagenomic studies.}, }
@article {pmid35369525, year = {2022}, author = {Wang, S and Song, F and Gu, H and Wei, X and Zhang, K and Zhou, Y and Luo, H}, title = {Comparative Evaluation of the Salivary and Buccal Mucosal Microbiota by 16S rRNA Sequencing for Forensic Investigations.}, journal = {Frontiers in microbiology}, volume = {13}, number = {}, pages = {777882}, pmid = {35369525}, issn = {1664-302X}, abstract = {The human microbiome has emerged as a new potential biomarker for forensic investigations with the development of high-throughput sequencing and bioinformatic analysis during the last decade. The oral cavity has many different microbial habitats, with each habit colonized by specific and individualized microbiota. As saliva and buccal mucosa are common biological evidence in forensic science, understanding the differences of microbial communities between the two is important for forensic original identification. Moreover, the oral microbiota is individualized, whereas there are few studies on the application of forensic personal identification that need to be supplemented. In this study, Streptococcus was the most abundant genus, with an average relative abundance of 49.61% in the buccal mucosa, while in the saliva, Streptococcus, Veillonella, and Neisseria had similar proportions (20%, 15%, 16%) and were the dominant genera. The α and β diversity displayed a significant distinctness between the saliva and buccal mucosal groups. The community assembly mechanism stated that the deterministic process played a more significant effect in shaping the salivary bacterial community assembly than buccal mucosa, which explained the microbial differences. Of the test samples, 93.3% can be correctly classified with the random forest model based on the microbial differences. Targeting the low-abundance bacteria at the species level, 52% of experimental participants could be discriminated by using the observed unique bacterial species. In conclusion, the salivary bacterial community composition differed from that of the buccal mucosa and showed high richness and diversity. With the random forest model, the microbiota of saliva and buccal mucosa can be classified, which can be used in identifying the source of oral biological trace. Furthermore, each individual has a unique bacterial community pattern, and the presence or absence of unique bacteria and differences in the composition of the core oral microbiota are the key points for forensic personal discrimination that supplement the study of oral microbial application to forensic personal discrimination. Whether for original identification or personal discrimination, the oral microbiome has great potential for application.}, }
@article {pmid35369083, year = {2022}, author = {Rees, J and Fu, SC and Lo, J and Sambell, R and Lewis, JR and Christophersen, CT and Byrne, MF and Newton, RU and Boyle, S and Devine, A}, title = {How a 7-Week Food Literacy Cooking Program Affects Cooking Confidence and Mental Health: Findings of a Quasi-Experimental Controlled Intervention Trial.}, journal = {Frontiers in nutrition}, volume = {9}, number = {}, pages = {802940}, pmid = {35369083}, issn = {2296-861X}, abstract = {Obesity and mental health disorders are rising simultaneously with shifting dietary behavior away from home cooking, toward typically nutrition-poor and energy-dense convenience meals. Food literacy strongly influences nutrition choices. Community-based cooking interventions target barriers to healthy eating and facilitate development of food literacy skills, thereby potentially increasing preparation of home-cooked meals and positively influencing health. This study of 657 healthy Australian adults explored the efficacy of a 7-week cooking program in improving cooking confidence, whether this transferred to behavior surrounding food, and/or affected mental health. Significant post-program improvements in cooking confidence and satisfaction (all p < 0.001, η p 2 1.12 large), ability to change eating habits (p < 0.001) and overcome lifestyle barriers (p = 0.005) were observed for the intervention group but not control. Participation also improved mental and general health (all p < 0.05, η p 2 0.02 small). No changes were observed for acquisition and consumption of food, or nutrition knowledge in either group. This 7-week cooking program built cooking confidence and improved general and mental health but did not change dietary behavior. To further improve nutrition related behaviors associated with better mental health, more effort is needed to recruit those with below-average nutrition knowledge and interest in cooking.}, }
@article {pmid35366966, year = {2022}, author = {Monir, RL and Schoch, JJ}, title = {Clinical Relevance of the Microbiome in Pediatric Skin Disease: A Review.}, journal = {Dermatologic clinics}, volume = {40}, number = {2}, pages = {117-126}, doi = {10.1016/j.det.2021.12.001}, pmid = {35366966}, issn = {1558-0520}, mesh = {*Alopecia Areata ; Child ; *Dermatitis, Atopic ; Humans ; *Microbiota ; Skin ; *Skin Diseases ; }, abstract = {The human microbiome encompasses the microorganisms that live in and on the body. During the prenatal and infantile periods, foundations for the cutaneous and gut microbiomes are being established and refined concurrently with the development of immune function. Herein, we review the relevance of the microbiome to 5 conditions commonly encountered in pediatric dermatology: acne, alopecia areata, atopic dermatitis, psoriasis, and seborrheic dermatitis. Understanding the role microbes play in these conditions may establish the groundwork for future therapeutic interventions.}, }
@article {pmid35366417, year = {2022}, author = {Patel, JR and Oh, J and Wang, S and Crawford, JM and Isaacs, FJ}, title = {Cross-kingdom expression of synthetic genetic elements promotes discovery of metabolites in the human microbiome.}, journal = {Cell}, volume = {185}, number = {9}, pages = {1487-1505.e14}, pmid = {35366417}, issn = {1097-4172}, support = {EP-W-17-011/EPA/EPA/United States ; R01 CA215553/CA/NCI NIH HHS/United States ; T32 GM067543/GM/NIGMS NIH HHS/United States ; }, mesh = {Bacteria/classification/genetics/metabolism ; *Biosynthetic Pathways ; Eukaryota/genetics/metabolism ; Genetic Engineering ; *Host Microbial Interactions ; Humans ; Metabolomics ; *Microbiota ; Synthetic Biology/*methods ; }, abstract = {Small molecules encoded by biosynthetic pathways mediate cross-species interactions and harbor untapped potential, which has provided valuable compounds for medicine and biotechnology. Since studying biosynthetic gene clusters in their native context is often difficult, alternative efforts rely on heterologous expression, which is limited by host-specific metabolic capacity and regulation. Here, we describe a computational-experimental technology to redesign genes and their regulatory regions with hybrid elements for cross-species expression in Gram-negative and -positive bacteria and eukaryotes, decoupling biosynthetic capacity from host-range constraints to activate silenced pathways. These synthetic genetic elements enabled the discovery of a class of microbiome-derived nucleotide metabolites-tyrocitabines-from Lactobacillus iners. Tyrocitabines feature a remarkable orthoester-phosphate, inhibit translational activity, and invoke unexpected biosynthetic machinery, including a class of "Amadori synthases" and "abortive" tRNA synthetases. Our approach establishes a general strategy for the redesign, expression, mobilization, and characterization of genetic elements in diverse organisms and communities.}, }
@article {pmid35366155, year = {2022}, author = {Sexton, RE and Uddin, MH and Bannoura, S and Khan, HY and Mzannar, Y and Li, Y and Aboukameel, A and Al-Hallak, MN and Al-Share, B and Mohamed, A and Nagasaka, M and El-Rayes, B and Azmi, AS}, title = {Connecting the Human Microbiome and Pancreatic Cancer.}, journal = {Cancer metastasis reviews}, volume = {41}, number = {2}, pages = {317-331}, pmid = {35366155}, issn = {1573-7233}, support = {R01 CA240607/CA/NCI NIH HHS/United States ; R37 CA215427/CA/NCI NIH HHS/United States ; }, mesh = {Humans ; *Microbiota ; Pancreas ; *Pancreatic Neoplasms/etiology ; }, abstract = {Pancreatic cancer is a deadly disease that is increasing in incidence throughout the world. There are no clear causal factors associated with the incidence of pancreatic cancer; however, some correlation to smoking, diabetes and alcohol has been described. Recently, a few studies have linked the human microbiome (oral and gastrointestinal tract) to pancreatic cancer development. A perturbed microbiome has been shown to alter normal cells while promoting cancer-related processes such as increased cell signaling, immune system evasion and invasion. In this article, we will review in detail the alterations within the gut and oral microbiome that have been linked to pancreatic cancer and explore the ability of other microbiomes, such as the lung and skin microbiome, to contribute to disease development. Understanding ways to identify a perturbed microbiome can result in advancements in pancreatic cancer research and allow for prevention, earlier detection and alternative treatment strategies for patients.}, }
@article {pmid35362479, year = {2022}, author = {Wensel, CR and Pluznick, JL and Salzberg, SL and Sears, CL}, title = {Next-generation sequencing: insights to advance clinical investigations of the microbiome.}, journal = {The Journal of clinical investigation}, volume = {132}, number = {7}, pages = {}, pmid = {35362479}, issn = {1558-8238}, support = {R01 HG006677/HG/NHGRI NIH HHS/United States ; 27140/CRUK_/Cancer Research UK/United Kingdom ; R35 GM130151/GM/NIGMS NIH HHS/United States ; A27140/CRUK_/Cancer Research UK/United Kingdom ; R01 CA196845/CA/NCI NIH HHS/United States ; R56 DK107726/DK/NIDDK NIH HHS/United States ; }, mesh = {High-Throughput Nucleotide Sequencing ; Humans ; Metagenomics/methods ; *Microbiota/genetics ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, RNA ; }, abstract = {Next-generation sequencing (NGS) technology has advanced our understanding of the human microbiome by allowing for the discovery and characterization of unculturable microbes with prediction of their function. Key NGS methods include 16S rRNA gene sequencing, shotgun metagenomic sequencing, and RNA sequencing. The choice of which NGS methodology to pursue for a given purpose is often unclear for clinicians and researchers. In this Review, we describe the fundamentals of NGS, with a focus on 16S rRNA and shotgun metagenomic sequencing. We also discuss pros and cons of each methodology as well as important concepts in data variability, study design, and clinical metadata collection. We further present examples of how NGS studies of the human microbiome have advanced our understanding of human disease pathophysiology across diverse clinical contexts, including the development of diagnostics and therapeutics. Finally, we share insights as to how NGS might further be integrated into and advance microbiome research and clinical care in the coming years.}, }
@article {pmid35360061, year = {2022}, author = {Reid, G and Dhir, R and Bron, PA}, title = {Fixing Functional GI Disorders Using Microbes: Easier Said Than Done.}, journal = {Frontiers in endocrinology}, volume = {13}, number = {}, pages = {804179}, pmid = {35360061}, issn = {1664-2392}, mesh = {*Gastrointestinal Diseases/therapy ; Humans ; }, }
@article {pmid35357819, year = {2022}, author = {Challa, AP and Hu, X and Zhang, YQ and Hymes, J and Wallace, BD and Karavadhi, S and Sun, H and Patnaik, S and Hall, MD and Shen, M}, title = {Virtual Screening for the Discovery of Microbiome β-Glucuronidase Inhibitors to Alleviate Cancer Drug Toxicity.}, journal = {Journal of chemical information and modeling}, volume = {62}, number = {7}, pages = {1783-1793}, pmid = {35357819}, issn = {1549-960X}, support = {R21 HD105304/HD/NICHD NIH HHS/United States ; UL1 TR002243/TR/NCATS NIH HHS/United States ; ZIA TR000362/ImNIH/Intramural NIH HHS/United States ; }, mesh = {*Antineoplastic Agents/adverse effects ; *Drug-Related Side Effects and Adverse Reactions ; Early Detection of Cancer ; Enzyme Inhibitors/pharmacology ; Glycoproteins ; Humans ; *Microbiota ; *Neoplasms ; }, abstract = {Despite the potency of most first-line anti-cancer drugs, nonadherence to these drug regimens remains high and is attributable to the prevalence of "off-target" drug effects that result in serious adverse events (SAEs) like hair loss, nausea, vomiting, and diarrhea. Some anti-cancer drugs are converted by liver uridine 5'-diphospho-glucuronosyltransferases through homeostatic host metabolism to form drug-glucuronide conjugates. These sugar-conjugated metabolites are generally inactive and can be safely excreted via the biliary system into the gastrointestinal tract. However, β-glucuronidase (βGUS) enzymes expressed by commensal gut bacteria can remove the glucuronic acid moiety, producing the reactivated drug and triggering dose-limiting side effects. Small-molecule βGUS inhibitors may reduce this drug-induced gut toxicity, allowing patients to complete their full course of treatment. Herein, we report the discovery of novel chemical series of βGUS inhibitors by structure-based virtual high-throughput screening (vHTS). We developed homology models for βGUS and applied them to large-scale vHTS against nearly 400,000 compounds within the chemical libraries of the National Center for Advancing Translational Sciences at the National Institutes of Health. From the vHTS results, we cherry-picked 291 compounds via a multifactor prioritization procedure, providing 69 diverse compounds that exhibited positive inhibitory activity in a follow-up βGUS biochemical assay in vitro. Our findings correspond to a hit rate of 24% and could inform the successful downstream development of a therapeutic adjunct that targets the human microbiome to prevent SAEs associated with first-line, standard-of-care anti-cancer drugs.}, }
@article {pmid35357498, year = {2022}, author = {Gomez-Raya-Vilanova, MV and Leskinen, K and Bhattacharjee, A and Virta, P and Rosenqvist, P and Smith, JLR and Bayfield, OW and Homberger, C and Kerrinnes, T and Vogel, J and Pajunen, MI and Skurnik, M}, title = {The DNA polymerase of bacteriophage YerA41 replicates its T-modified DNA in a primer-independent manner.}, journal = {Nucleic acids research}, volume = {50}, number = {7}, pages = {3985-3997}, pmid = {35357498}, issn = {1362-4962}, support = {/WT_/Wellcome Trust/United Kingdom ; 206377/WT_/Wellcome Trust/United Kingdom ; }, mesh = {*Bacteriophages/chemistry/genetics ; Capsid ; Cryoelectron Microscopy ; DNA, Viral/genetics ; DNA-Directed DNA Polymerase/genetics ; Genome, Viral/genetics ; Thymidine ; }, abstract = {Yersinia phage YerA41 is morphologically similar to jumbo bacteriophages. The isolated genomic material of YerA41 could not be digested by restriction enzymes, and used as a template by conventional DNA polymerases. Nucleoside analysis of the YerA41 genomic material, carried out to find out whether this was due to modified nucleotides, revealed the presence of a ca 1 kDa substitution of thymidine with apparent oligosaccharide character. We identified and purified the phage DNA polymerase (DNAP) that could replicate the YerA41 genomic DNA even without added primers. Cryo-electron microscopy (EM) was used to characterize structural details of the phage particle. The storage capacity of the 131 nm diameter head was calculated to accommodate a significantly longer genome than that of the 145 577 bp genomic DNA of YerA41 determined here. Indeed, cryo-EM revealed, in contrast to the 25 Å in other phages, spacings of 33-36 Å between shells of the genomic material inside YerA41 heads suggesting that the heavily substituted thymidine increases significantly the spacing of the DNA packaged inside the capsid. In conclusion, YerA41 appears to be an unconventional phage that packages thymidine-modified genomic DNA into its capsids along with its own DNAP that has the ability to replicate the genome.}, }
@article {pmid35355602, year = {2022}, author = {Montemari, AL and Marzano, V and Essa, N and Levi Mortera, S and Rossitto, M and Gardini, S and Selan, L and Vrenna, G and Onetti Muda, A and Putignani, L and Fiscarelli, EV}, title = {A Shaving Proteomic Approach to Unveil Surface Proteins Modulation of Multi-Drug Resistant Pseudomonas aeruginosa Strains Isolated From Cystic Fibrosis Patients.}, journal = {Frontiers in medicine}, volume = {9}, number = {}, pages = {818669}, pmid = {35355602}, issn = {2296-858X}, abstract = {Cystic fibrosis (CF) is the most common rare disease caused by a mutation of the CF transmembrane conductance regulator gene encoding a channel protein of the apical membrane of epithelial cells leading to alteration of Na[+] and K[+] transport, hence inducing accumulation of dense and sticky mucus and promoting recurrent airway infections. The most detected bacterium in CF patients is Pseudomonas aeruginosa (PA) which causes chronic colonization, requiring stringent antibiotic therapies that, in turn induces multi-drug resistance. Despite eradication attempts at the first infection, the bacterium is able to utilize several adaptation mechanisms to survive in hostile environments such as the CF lung. Its adaptive machinery includes modulation of surface molecules such as efflux pumps, flagellum, pili and other virulence factors. In the present study we compared surface protein expression of PA multi- and pan-drug resistant strains to wild-type antibiotic-sensitive strains, isolated from the airways of CF patients with chronic colonization and recent infection, respectively. After shaving with trypsin, microbial peptides were analyzed by tandem-mass spectrometry on a high-resolution platform that allowed the identification of 174 differentially modulated proteins localized in the region from extracellular space to cytoplasmic membrane. Biofilm assay was performed to characterize all 26 PA strains in term of biofilm production. Among the differentially expressed proteins, 17 were associated to the virulome (e.g., Tse2, Tse5, Tsi1, PilF, FliY, B-type flagellin, FliM, PyoS5), six to the resistome (e.g., OprJ, LptD) and five to the biofilm reservoir (e.g., AlgF, PlsD). The biofilm assay characterized chronic antibiotic-resistant isolates as weaker biofilm producers than wild-type strains. Our results suggest the loss of PA early virulence factors (e.g., pili and flagella) and later expression of virulence traits (e.g., secretion systems proteins) as an indicator of PA adaptation and persistence in the CF lung environment. To our knowledge, this is the first study that, applying a shaving proteomic approach, describes adaptation processes of a large collection of PA clinical strains isolated from CF patients in early and chronic infection phases.}, }
@article {pmid35355005, year = {2022}, author = {Kamdar, S and Shin, S and Leishangthem, P and Francis, LF and Xu, X and Cheng, X}, title = {The colloidal nature of complex fluids enhances bacterial motility.}, journal = {Nature}, volume = {603}, number = {7903}, pages = {819-823}, pmid = {35355005}, issn = {1476-4687}, mesh = {Bacteria ; *Colloids ; *Ecosystem ; Humans ; Hydrodynamics ; Polymers ; }, abstract = {The natural habitats of microorganisms in the human microbiome, ocean and soil ecosystems are full of colloids and macromolecules. Such environments exhibit non-Newtonian flow properties, drastically affecting the locomotion of microorganisms[1-5]. Although the low-Reynolds-number hydrodynamics of swimming flagellated bacteria in simple Newtonian fluids has been well developed[6-9], our understanding of bacterial motility in complex non-Newtonian fluids is less mature[10,11]. Even after six decades of research, fundamental questions about the nature and origin of bacterial motility enhancement in polymer solutions are still under debate[12-23]. Here we show that flagellated bacteria in dilute colloidal suspensions display quantitatively similar motile behaviours to those in dilute polymer solutions, in particular a universal particle-size-dependent motility enhancement up to 80% accompanied by a strong suppression of bacterial wobbling[18,24]. By virtue of the hard-sphere nature of colloids, whose size and volume fraction we vary across experiments, our results shed light on the long-standing controversy over bacterial motility enhancement in complex fluids and suggest that polymer dynamics may not be essential for capturing the phenomenon[12-23]. A physical model that incorporates the colloidal nature of complex fluids quantitatively explains bacterial wobbling dynamics and mobility enhancement in both colloidal and polymeric fluids. Our findings contribute to the understanding of motile behaviours of bacteria in complex fluids, which are relevant for a wide range of microbiological processes[25] and for engineering bacterial swimming in complex environments[26,27].}, }
@article {pmid35344737, year = {2022}, author = {Houttu, N and Mokkala, K and Saleem, WT and Virtanen, S and Juhila, J and Koivuniemi, E and Pellonperä, O and Tertti, K and Luokola, P and Sorsa, T and Salonen, A and Lahti, L and Laitinen, K}, title = {Potential pathobionts in vaginal microbiota are affected by fish oil and/or probiotics intervention in overweight and obese pregnant women.}, journal = {Biomedicine &amp; pharmacotherapy = Biomedecine &amp; pharmacotherapie}, volume = {149}, number = {}, pages = {112841}, doi = {10.1016/j.biopha.2022.112841}, pmid = {35344737}, issn = {1950-6007}, mesh = {*Bifidobacterium animalis ; C-Reactive Protein ; *Diabetes, Gestational ; Female ; Fish Oils/therapeutic use ; Humans ; Insulin-Like Growth Factor Binding Protein 1 ; *Lacticaseibacillus rhamnosus ; *Microbiota ; Obesity/therapy ; Overweight/therapy ; Pregnancy ; Pregnant People ; *Probiotics/therapeutic use ; RNA, Ribosomal, 16S ; }, abstract = {New means to stabilize the microbial balance during pregnancy could benefit maternal health. Our objectives were to investigate in overweight/obese pregnant women 1) the impact of long-chain polyunsaturated fatty acids (fish oil) and/or probiotics on the vaginal microbiota, 2) its relation to gestational diabetes mellitus (GDM) and 3) its interaction with vaginal active matrix metalloproteinase-8 (aMMP-8) and serum high sensitivity C-reactive protein (hsCRP) and phosphorylated insulin-like growth factor-binding protein-1 (phIGFBP-1), IGFBP-1 and aMMP-8. The women were allocated to fish oil + placebo, probiotics + placebo, fish oil + probiotics and placebo + placebo-groups, from early pregnancy onwards (fish oil: 1.9 g docosahexaenoic acid and 0.22 g eicosapentaenoic acid; probiotics: Lacticaseibacillus rhamnosus HN001 (formerly Lactobacillus rhamnosus HN001) and Bifidobacterium animalis ssp. lactis 420, 10[10] colony-forming units each). Vaginal and serum samples (early pregnancy, n = 112; late pregnancy, n = 116), were analyzed for vaginal microbiota using 16S rRNA gene amplicon sequencing and vaginal aMMP-8 and serum hsCRP, aMMP-8, phIGFBP-1 and IGFBP-1 by immunoassays. GDM was diagnosed from a 2-h 75 g OGTT. ClinicalTrials.gov, NCT01922791. The intervention exerted effects on many low-abundant bacteria. Compared to the placebo-group, there was a lower abundance of potential pathobionts, namely Ureaplasma urealyticum in the fish oil-group, Ureaplasma, U. urealyticum and Prevotella disiens in the probiotics-group, Dialister invisus and Prevotella timonensis in the fish oil + probiotics-group. Moreover, probiotics decreased the abundance of a few potential pathobionts during pregnancy. Many bacteria were related to GDM. The vaginal aMMP-8 level correlated significantly with α-diversity and inversely with two Lactobacillus species. Dietary interventions, especially probiotics, may have beneficial effects on the vaginal microbiota during pregnancy.}, }
@article {pmid35343759, year = {2022}, author = {Berlinberg, AJ and Brar, A and Stahly, A and Gerich, ME and Fennimore, BP and Scott, FI and Kuhn, KA}, title = {A Novel Approach toward Less Invasive Multiomics Gut Analyses: a Pilot Study.}, journal = {Microbiology spectrum}, volume = {10}, number = {2}, pages = {e0244621}, pmid = {35343759}, issn = {2165-0497}, support = {T32 AR007534/AR/NIAMS NIH HHS/United States ; R01 AR075033/AR/NIAMS NIH HHS/United States ; P30 CA046934/CA/NCI NIH HHS/United States ; }, mesh = {Feces ; *Gastrointestinal Microbiome ; Humans ; Metabolomics/methods ; *Microbiota ; Pilot Projects ; }, abstract = {Newer 'omics approaches, such as metatranscriptomics and metabolomics, allow functional assessments of the interaction(s) between the gut microbiome and the human host. However, in order to generate meaningful data with these approaches, the method of sample collection is critical. Prior studies have relied on expensive and invasive means toward sample acquisition, such as intestinal biopsy, while other studies have relied on easier methods of collection, such as fecal samples that do not necessarily represent those microbes in contact with the host. In this pilot study, we attempt to characterize a novel, minimally invasive method toward sampling the human microbiome using mucosal cytology brush sampling compared to intestinal gut biopsy samples on 5 healthy participants undergoing routine screening colonoscopy. We compared metatranscriptomic analyses between the two collection methods and identified increased taxonomic evenness and beta diversity in the cytology brush samples and similar community transcriptional profiles between the two methods. Metabolomics assessment demonstrated striking differences between the two methods, implying a difference in bacterial-derived versus human-absorbed metabolites. Put together, this study supports the use of microbiome sampling with cytology brushes, but caution must be exercised when performing metabolomics assessment, as this represents differential metabolite production but not absorption by the host. IMPORTANCE In order to generate meaningful metabolomic and microbiome data, the method of sample collection is critical. This study utilizes and compares two methods for intestinal tissue collection for evaluation of metabolites and microbiomes, finding that using a brush to sample the microbiome provides valuable data. However, for metabolomics assessment, biopsy samples may still be required.}, }
@article {pmid35340443, year = {2022}, author = {Schiller, H and Young, C and Schulze, S and Tripepi, M and Pohlschroder, M}, title = {A Twist to the Kirby-Bauer Disk Diffusion Susceptibility Test: an Accessible Laboratory Experiment Comparing Haloferax volcanii and Escherichia coli Antibiotic Susceptibility to Highlight the Unique Cell Biology of Archaea.}, journal = {Journal of microbiology &amp; biology education}, volume = {23}, number = {1}, pages = {}, pmid = {35340443}, issn = {1935-7877}, abstract = {Archaea, once thought to only live in extreme environments, are present in many ecosystems, including the human microbiome, and they play important roles ranging from nutrient cycling to bioremediation. Yet this domain is often overlooked in microbiology classes and rarely included in laboratory exercises. Excluding archaea from high school and undergraduate curricula prevents students from learning the uniqueness and importance of this domain. Here, we have modified a familiar and popular microbiology experiment-the Kirby-Bauer disk diffusion antibiotic susceptibility test-to include, together with the model bacterium Escherichia coli, the model archaeon Haloferax volcanii. Students will learn the differences and similarities between archaea and bacteria by using antibiotics that target, for example, the bacterial peptidoglycan cell wall or the ribosome. Furthermore, the experiment provides a platform to reiterate basic cellular biology concepts that students may have previously discussed. We have developed two versions of this experiment, one designed for an undergraduate laboratory curriculum and the second, limited to H. volcanii, that high school students can perform in their classrooms. This nonpathogenic halophile can be cultured aerobically at ambient temperature in high-salt media, preventing contamination, making the experiment low-cost and safe for use in the high school setting.}, }
@article {pmid35338496, year = {2022}, author = {Palacios-García, I and Mhuireach, GA and Grasso-Cladera, A and Cryan, JF and Parada, FJ}, title = {The 4E approach to the human microbiome: Nested interactions between the gut-brain/body system within natural and built environments.}, journal = {BioEssays : news and reviews in molecular, cellular and developmental biology}, volume = {44}, number = {6}, pages = {e2100249}, doi = {10.1002/bies.202100249}, pmid = {35338496}, issn = {1521-1878}, mesh = {Brain/physiology ; Built Environment ; Cognition/physiology ; *Gastrointestinal Microbiome/physiology ; Humans ; *Microbiota ; }, abstract = {The complexity of the human mind and its interaction with the environment is one of the main epistemological debates throughout history. Recent ideas, framed as the 4E perspective to cognition, highlight that human experience depends causally on both cerebral and extracranial processes, but also is embedded in a particular sociomaterial context and is a product of historical accumulation of trajectory changes throughout life. Accordingly, the human microbiome is one of the most intriguing actors modulating brain function and physiology. Here, we present the 4E approach to the Human Microbiome for understanding mental processes from a broader perspective, encompassing one's body physiology and environment throughout their lifespan, interconnected by microbiome community structure and dynamics. We review evidence supporting the approach theoretically and motivates the study of the global set of microbial ecosystem networks encountered by a person across their lifetime (from skin to gut to natural and built environments). We furthermore trace future empirical implementation of the approach. We finally discuss novel research opportunities and clinical interventions aimed toward developing low-cost/high-benefit integrative and personalized bio-psycho-socio-environmental treatments for mental health and including the brain-gut-microbiome axis.}, }
@article {pmid35336128, year = {2022}, author = {Ji, D and Sun, H and Yang, W and Gao, M and Xu, H}, title = {Transfer of Human Microbiome to Drosophila Gut Model.}, journal = {Microorganisms}, volume = {10}, number = {3}, pages = {}, pmid = {35336128}, issn = {2076-2607}, abstract = {Laboratory animals with human microbiome have increasingly been used to study the role of bacteria and host interaction. Drosophila melanogaster, as a model of microbiota-host interaction with high reproductive efficiency and high availability, has always been lacking studies of interaction with human gut microbiome. In this study, we attempted to use antibiotic therapy and human fecal exposure strategy to transfer the human microbiome to the drosophila. The method includes depleting the original intestinal bacteria using a broad-spectrum antibiotic and then introducing human microorganisms by a diet supplemented with donor's fecal samples. The sequencing results showed that 80-87.5% of the OTUs (Operational Taxonomic Units) from donor feces were adopted by the recipient drosophila following 30 days of observation. In comparison to females, the male recipient drosophila inherited more microbiota from the donor feces and had significantly increased lifespan as well as improved vertical climbing ability. Furthermore, distinctly differential expression patterns for age and insulin-like signaling-related genes were obtained for the male vs. female recipients. Only the male drosophila offspring acquired the characteristics of the donor fecal microbiota.}, }
@article {pmid35332832, year = {2022}, author = {Crits-Christoph, A and Hallowell, HA and Koutouvalis, K and Suez, J}, title = {Good microbes, bad genes? The dissemination of antimicrobial resistance in the human microbiome.}, journal = {Gut microbes}, volume = {14}, number = {1}, pages = {2055944}, pmid = {35332832}, issn = {1949-0984}, support = {DP5 OD029603/OD/NIH HHS/United States ; }, mesh = {Anti-Bacterial Agents/pharmacology ; Bacteria/genetics ; Drug Resistance, Bacterial/genetics ; *Gastrointestinal Microbiome/genetics ; Genes, Bacterial ; Humans ; Metagenomics ; *Microbiota/genetics ; }, abstract = {A global rise in antimicrobial resistance among pathogenic bacteria has proved to be a major public health threat, with the rate of multidrug-resistant bacterial infections increasing over time. The gut microbiome has been studied as a reservoir of antibiotic resistance genes (ARGs) that can be transferred to bacterial pathogens via horizontal gene transfer (HGT) of conjugative plasmids and mobile genetic elements (the gut resistome). Advances in metagenomic sequencing have facilitated the identification of resistome modulators, including live microbial therapeutics such as probiotics and fecal microbiome transplantation that can either expand or reduce the abundances of ARG-carrying bacteria in the gut. While many different gut microbes encode for ARGs, they are not uniformly distributed across, or transmitted by, various members of the microbiome, and not all are of equal clinical relevance. Both experimental and theoretical approaches in microbial ecology have been applied to understand differing frequencies of ARG horizontal transfer between commensal microbes as well as between commensals and pathogens. In this commentary, we assess the evidence for the role of commensal gut microbes in encoding antimicrobial resistance genes, the degree to which they are shared both with other commensals and with pathogens, and the host and environmental factors that can impact resistome dynamics. We further discuss novel sequencing-based approaches for identifying ARGs and predicting future transfer events of clinically relevant ARGs from commensals to pathogens.}, }
@article {pmid35330207, year = {2022}, author = {Panthee, B and Gyawali, S and Panthee, P and Techato, K}, title = {Environmental and Human Microbiome for Health.}, journal = {Life (Basel, Switzerland)}, volume = {12}, number = {3}, pages = {}, pmid = {35330207}, issn = {2075-1729}, abstract = {Microorganisms are an essential part of life on the earth and can exist in association with virtually any living thing. The environmental microbiome is much more diverse than the human microbiome. It is reported that most microbes existing in the environment are difficult to culture in the laboratory. Whereas both pathogenic and beneficial microbes may be prevailing in the environment, the human body can have three categories of microbes- beneficial, pathogenic, and opportunistic pathogenic. With at least 10-fold more cells than human cells, microbes as normal flora are critical for human survival. The microbes present in the human body play a crucial role in maintaining human health, and the environmental microbiome influences the human microbiome makeup. The interaction between the environmental and human microbiome highly influences human health, however it is poorly understood. In addition, as an established infection is associated with health-seeking behavior, a large number of studies have focused on the transmission and dynamics of infectious microorganisms than the noninfectious or beneficial ones. This review will summarize how the interaction between the environmental and human microbiome affects human health and identify approaches that might be beneficial for humans to improve health by being exposed to the natural environment.}, }
@article {pmid35324141, year = {2022}, author = {Adelfio, M and Ghezzi, CE}, title = {Long-Term In Vitro Culture Systems to Study Human Microbiome.}, journal = {ACS biomaterials science &amp; engineering}, volume = {8}, number = {11}, pages = {4613-4617}, pmid = {35324141}, issn = {2373-9878}, support = {R03 DE030224/DE/NIDCR NIH HHS/United States ; }, mesh = {Animals ; Humans ; *Dysbiosis ; *Microbiota ; Mammals ; }, abstract = {Microbial communities are eubiotic ecosystems that interact dynamically and synergistically with the human body. Imbalances in these interactions may cause dysbiosis by enhancing the occurrence of inflammatory conditions, such as periodontal or inflammatory bowel diseases. However, the mechanisms that lie behind eubiosis-dysbiosis transitions are still unclear and constantly being redefined. While the societal impact of these diseases is steadily increasing, the lack of a clear understanding behind the onset of the inflammatory conditions prevents the proper clinical strategies from being formulated. Although preclinical and clinical models and short-term planar in vitro cultures represent superb research tools, they are still lacking human relevance and long-term use. Bioreactors and organs-on-a-chip have attracted interest because of their ability to recreate and sustain the physical, structural, and mechanical features of the native environment, as well as to support long-term coculture of mammalian cells and the microbiome through modulation of pH and oxygen gradients. Existing devices, however, are still under development to sustain the microbiome-host coculture over long periods of time. In this scenario, to understand disease triggers and develop therapeutics, research efforts should command the development of three-dimensional constructs that would allow the investigation of processes underlying the microbial community assembly and how microorganisms influence host traits in both acute and chronic conditions.}, }
@article {pmid35321316, year = {2022}, author = {Carmona-Cruz, S and Orozco-Covarrubias, L and Sáez-de-Ocariz, M}, title = {The Human Skin Microbiome in Selected Cutaneous Diseases.}, journal = {Frontiers in cellular and infection microbiology}, volume = {12}, number = {}, pages = {834135}, pmid = {35321316}, issn = {2235-2988}, mesh = {*Alopecia Areata ; *Dermatitis, Atopic ; Humans ; *Microbiota ; *Psoriasis ; Skin ; }, abstract = {The human skin harbors a wide variety of microbes that, together with their genetic information and host interactions, form the human skin microbiome. The role of the human microbiome in the development of various diseases has lately gained interest. According to several studies, changes in the cutaneous microbiota are involved in the pathophysiology of several dermatoses. A better delineation of the human microbiome and its interactions with the innate and adaptive immune systems could lead to a better understanding of these diseases, as well as the opportunity to achieve new therapeutic modalities. The present review centers on the most recent knowledge on skin microbiome and its participation in the pathogenesis of several skin disorders: atopic and seborrheic dermatitis, alopecia areata, psoriasis and acne.}, }
@article {pmid35318071, year = {2022}, author = {Chen, M and Fan, HN and Chen, XY and Yi, YC and Zhang, J and Zhu, JS}, title = {Alterations in the saliva microbiome in patients with gastritis and small bowel inflammation.}, journal = {Microbial pathogenesis}, volume = {165}, number = {}, pages = {105491}, doi = {10.1016/j.micpath.2022.105491}, pmid = {35318071}, issn = {1096-1208}, mesh = {Dysbiosis/microbiology ; *Enteritis ; *Gastritis/microbiology ; Humans ; Inflammation/microbiology ; *Microbiota ; RNA, Ribosomal, 16S/genetics ; Saliva/microbiology ; }, abstract = {The oral microbiome is an important part of the human microbiome. Accumulating data have shown that oral microbiome alterations are closely related to multiple human diseases. However, salivary microbiota distributions remain unclear in patients with gastritis and small bowel inflammation. Magnetically guided capsule endoscopy (MGCE) is a noninvasive diagnostic tool for patients with gastritis and small bowel inflammation. Herein, we analysed the alterations in saliva microbiota in the normal, small intestinal inflammation and chronic gastritis groups through 16S rRNA gene amplicon sequencing. We found that the abundance of Lactobacillaceae was dramatically higher in chronic gastritis group than healthy individuals (p = 0.001). The levels of Porphyromonas and Faecalibaculum in gastritis samples were increased (p = 0.028; p = 0.006), and the enrichments of Faecalibaculum and Kosakonia in small intestine inflammation samples were elevated (p < 0.001; p = 0.002) compared to those in normal individuals. Our findings clarify the saliva microbiota components and their importance of specific bacteria in gastritis and small bowel inflammation.}, }
@article {pmid35303139, year = {2022}, author = {Bernabé, BP and Maki, PM and Dowty, SM and Salas, MLC and Shah, Z and Gilbert, JA}, title = {Correction to: Precision medicine in perinatal depression in light of the human microbiome.}, journal = {Psychopharmacology}, volume = {239}, number = {7}, pages = {2367}, doi = {10.1007/s00213-022-06102-y}, pmid = {35303139}, issn = {1432-2072}, }
@article {pmid35302439, year = {2022}, author = {Gehrig, JL and Portik, DM and Driscoll, MD and Jackson, E and Chakraborty, S and Gratalo, D and Ashby, M and Valladares, R}, title = {Finding the right fit: evaluation of short-read and long-read sequencing approaches to maximize the utility of clinical microbiome data.}, journal = {Microbial genomics}, volume = {8}, number = {3}, pages = {}, pmid = {35302439}, issn = {2057-5858}, mesh = {Humans ; Metagenome/genetics ; Metagenomics/methods ; *Microbiota/genetics ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA/methods ; }, abstract = {A long-standing challenge in human microbiome research is achieving the taxonomic and functional resolution needed to generate testable hypotheses about the gut microbiota's impact on health and disease. With a growing number of live microbial interventions in clinical development, this challenge is renewed by a need to understand the pharmacokinetics and pharmacodynamics of therapeutic candidates. While short-read sequencing of the bacterial 16S rRNA gene has been the standard for microbiota profiling, recent improvements in the fidelity of long-read sequencing underscores the need for a re-evaluation of the value of distinct microbiome-sequencing approaches. We leveraged samples from participants enrolled in a phase 1b clinical trial of a novel live biotherapeutic product to perform a comparative analysis of short-read and long-read amplicon and metagenomic sequencing approaches to assess their utility for generating clinical microbiome data. Across all methods, overall community taxonomic profiles were comparable and relationships between samples were conserved. Comparison of ubiquitous short-read 16S rRNA amplicon profiling to long-read profiling of the 16S-ITS-23S rRNA amplicon showed that only the latter provided strain-level community resolution and insight into novel taxa. All methods identified an active ingredient strain in treated study participants, though detection confidence was higher for long-read methods. Read coverage from both metagenomic methods provided evidence of active-ingredient strain replication in some treated participants. Compared to short-read metagenomics, approximately twice the proportion of long reads were assigned functional annotations. Finally, compositionally similar bacterial metagenome-assembled genomes (MAGs) were recovered from short-read and long-read metagenomic methods, although a greater number and more complete MAGs were recovered from long reads. Despite higher costs, both amplicon and metagenomic long-read approaches yielded added microbiome data value in the form of higher confidence taxonomic and functional resolution and improved recovery of microbial genomes compared to traditional short-read methodologies.}, }
@article {pmid35301310, year = {2022}, author = {Forster, SC and Liu, J and Kumar, N and Gulliver, EL and Gould, JA and Escobar-Zepeda, A and Mkandawire, T and Pike, LJ and Shao, Y and Stares, MD and Browne, HP and Neville, BA and Lawley, TD}, title = {Strain-level characterization of broad host range mobile genetic elements transferring antibiotic resistance from the human microbiome.}, journal = {Nature communications}, volume = {13}, number = {1}, pages = {1445}, pmid = {35301310}, issn = {2041-1723}, support = {/WT_/Wellcome Trust/United Kingdom ; 206194/WT_/Wellcome Trust/United Kingdom ; }, mesh = {Animals ; Anti-Bacterial Agents/pharmacology ; Bacteria/genetics ; Drug Resistance, Microbial/genetics ; Genes, Bacterial ; *Host Specificity/genetics ; Humans ; Interspersed Repetitive Sequences/genetics ; *Microbiota/genetics ; }, abstract = {Mobile genetic elements (MGEs) carrying antibiotic resistance genes (ARGs) disseminate ARGs when they mobilise into new bacterial hosts. The nature of such horizontal gene transfer (HGT) events between human gut commensals and pathogens remain poorly characterised. Here, we compare 1354 cultured commensal strains (540 species) to 45,403 pathogen strains (12 species) and find 64,188 MGE-mediated ARG transfer events between the two groups using established methods. Among the 5931 MGEs, we find 15 broad host range elements predicted to have crossed different bacterial phyla while also occurring in animal and environmental microbiomes. We experimentally demonstrate that predicted broad host range MGEs can mobilise from commensals Dorea longicatena and Hungatella hathewayi to pathogen Klebsiella oxytoca, crossing phyla simultaneously. Our work establishes the MGE-mediated ARG dissemination network between human gut commensals and pathogens and highlights broad host range MGEs as targets for future ARG dissemination management.}, }
@article {pmid35295290, year = {2022}, author = {Zioutis, C and Seki, D and Bauchinger, F and Herbold, C and Berger, A and Wisgrill, L and Berry, D}, title = {Ecological Processes Shaping Microbiomes of Extremely Low Birthweight Infants.}, journal = {Frontiers in microbiology}, volume = {13}, number = {}, pages = {812136}, pmid = {35295290}, issn = {1664-302X}, support = {DOC 69/FWF_/Austrian Science Fund FWF/Austria ; P 27831/FWF_/Austrian Science Fund FWF/Austria ; }, abstract = {The human microbiome has been implicated in affecting health outcomes in premature infants, but the ecological processes governing early life microbiome assembly remain poorly understood. Here, we investigated microbial community assembly and dynamics in extremely low birth weight infants (ELBWI) over the first 2 weeks of life. We profiled the gut, oral cavity and skin microbiomes over time using 16S rRNA gene amplicon sequencing and evaluated the ecological forces shaping these microbiomes. Though microbiomes at all three body sites were characterized by compositional instability over time and had low body-site specificity (PERMANOVA, r [2] = 0.09, p = 0.001), they could nonetheless be clustered into four discrete community states. Despite the volatility of these communities, deterministic assembly processes were detectable in this period of initial microbial colonization. To further explore these deterministic dynamics, we developed a probabilistic approach in which we modeled microbiome state transitions in each ELBWI as a Markov process, or a "memoryless" shift, from one community state to another. This analysis revealed that microbiomes from different body sites had distinctive dynamics as well as characteristic equilibrium frequencies. Time-resolved microbiome sampling of premature infants may help to refine and inform clinical practices. Additionally, this work provides an analysis framework for microbial community dynamics based on Markov modeling that can facilitate new insights, not only into neonatal microbiomes but also other human-associated or environmental microbiomes.}, }
@article {pmid35288482, year = {2021}, author = {Launonen, H and Pang, Z and Linden, J and Siltari, A and Korpela, R and Vapaatalo, H}, title = {Evidence for local aldosterone synthesis in the large intestine of the mouse.}, journal = {Journal of physiology and pharmacology : an official journal of the Polish Physiological Society}, volume = {72}, number = {5}, pages = {}, doi = {10.26402/jpp.2021.5.15}, pmid = {35288482}, issn = {1899-1505}, mesh = {*Adrenal Cortex/metabolism ; *Aldosterone/biosynthesis ; Animals ; *Colon/metabolism ; *Cytochrome P-450 CYP11B2/genetics/metabolism ; Male ; Mice ; Sodium/metabolism ; }, abstract = {Aldosterone, the main physiological mineralocorticoid, regulates sodium and potassium balance in the distal convoluted tubule of the kidney. Aldosterone is synthesized from cholesterol in the adrenal cortex in a sequence of enzymatic steps. Recently however, several tissues or cells e.g. brain, heart, blood vessels, kidneys and adipocytes have been shown to possess capability to produce aldosterone locally, and there is some evidence that this occurs also in the intestine. Colon expresses mineralocorticoid receptors and is capable of synthesizing corticosterone, the second last intermediate on the route to aldosterone from cholesterol. Based on such reports and on our preliminary finding, we hypothesized that aldosterone could be synthesized locally in the intestine and therefore we measured the concentration of aldosterone as well as the protein and gene expression of aldosterone synthase (CYP11B2), an enzyme responsible on aldosterone synthesis, from the distal section of the gastrointestinal tract of 10-week-old Balb/c male mice. It is known that sodium deficiency regulates aldosterone synthesis in adrenal glands, therefore we fed the mice with low (0.01%), normal (0.2%) and high-sodium (1.6%) diets for 14 days. Here we report that, aldosterone was detected in colon and cecum samples. Measurable amounts of CYP11B2 protein were detected by Western blot and Elisa analysis from both intestinal tissues. We detected CYP11B2 gene expression from the large intestine along with immunohistochemical findings of CYP11B2 in colonic wall. Sodium depletion increased the aldosterone concentration in plasma compared to control and high-sodium groups as well as in the intestine compared to mice fed with the high-sodium diet. To summarize, this study further supports the presence of aldosterone and the enzyme needed to produce this mineralocorticoid in the murine large intestine.}, }
@article {pmid35278679, year = {2022}, author = {Wani, AK and Roy, P and Kumar, V and Mir, TUG}, title = {Metagenomics and artificial intelligence in the context of human health.}, journal = {Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases}, volume = {100}, number = {}, pages = {105267}, doi = {10.1016/j.meegid.2022.105267}, pmid = {35278679}, issn = {1567-7257}, mesh = {Artificial Intelligence ; DNA ; Humans ; *Metagenomics/methods ; *Microbiota/genetics ; Sequence Analysis, DNA ; }, abstract = {Human microbiome is ubiquitous, dynamic, and site-specific consortia of microbial communities. The pathogenic nature of microorganisms within human tissues has led to an increase in microbial studies. Characterization of genera, like Streptococcus, Cutibacterium, Staphylococcus, Bifidobacterium, Lactococcus and Lactobacillus through culture-dependent and culture-independent techniques has been reported. However, due to the unique environment within human tissues, it is difficult to culture these microorganisms making their molecular studies strenuous. MGs offer a gateway to explore and characterize hidden microbial communities through a culture-independent mode by direct DNA isolation. By function and sequence-based MGs, Scientists can explore the mechanistic details of numerous microbes and their interaction with the niche. Since the data generated from MGs studies is highly complex and multi-dimensional, it requires accurate analytical tools to evaluate and interpret the data. Artificial intelligence (AI) provides the luxury to automatically learn the data dimensionality and ease its complexity that makes the disease diagnosis and disease response easy, accurate and timely. This review provides insight into the human microbiota and its exploration and expansion through MG studies. The review elucidates the significance of MGs in studying the changing microbiota during disease conditions besides highlighting the role of AI in computational analysis of MG data.}, }
@article {pmid35273169, year = {2022}, author = {Cai, YY and Huang, FQ and Lao, X and Lu, Y and Gao, X and Alolga, RN and Yin, K and Zhou, X and Wang, Y and Liu, B and Shang, J and Qi, LW and Li, J}, title = {Integrated metagenomics identifies a crucial role for trimethylamine-producing Lachnoclostridium in promoting atherosclerosis.}, journal = {NPJ biofilms and microbiomes}, volume = {8}, number = {1}, pages = {11}, pmid = {35273169}, issn = {2055-5008}, mesh = {Animals ; *Atherosclerosis ; Choline ; *Gastrointestinal Microbiome ; Humans ; Metagenomics ; Methylamines ; Mice ; }, abstract = {Microbial trimethylamine (TMA)-lyase activity promotes the development of atherosclerosis by generating of TMA, the precursor of TMA N-oxide (TMAO). TMAO is well documented, but same can not be said of TMA-producing bacteria. This work aimed to identify TMA-producing genera in human intestinal microbiota. We retrieved the genomes of human-associated microorganisms from the Human Microbiome Project database comprising 1751 genomes, Unified Human Gastrointestinal Genome collection consisting 4644 gut prokaryotes, recapitulated 4930 species-level genome bins and public gut metagenomic data of 2134 individuals from 11 populations. By sequence searching, 216 TMA-lyase-containing species from 102 genera were found to contain the homologous sequences of cntA/B, yeaW/X, and/or cutC/D. We identified 13 strains from 5 genera with cntA sequences, and 30 strains from 14 genera with cutC showing detectable relative abundance in healthy individuals. Lachnoclostridium (p = 2.9e-05) and Clostridium (p = 5.8e-04), the two most abundant cutC-containing genera, were found to be much higher in atherosclerotic patients compared with healthy persons. Upon incubation with choline (substrate), L. saccharolyticum effectively transformed it to TMA at a rate higher than 98.7% while that for C. sporogenes was 63.8-67.5% as detected by liquid chromatography-triple quadrupole mass spectrometry. In vivo studies further showed that treatment of L. saccharolyticum and choline promoted a significant increase in TMAO level in the serum of ApoE[-/-] mice with obvious accumulation of aortic plaque in same. This study discloses the significance and efficiency of the gut bacterium L. saccharolyticum in transforming choline to TMA and consequently promoting the development of atherosclerosis.}, }
@article {pmid35272051, year = {2022}, author = {Zhou, F and Gan, R and Zhang, F and Ren, C and Yu, L and Si, Y and Huang, Z}, title = {PHISDetector: A Tool to Detect Diverse In Silico Phage-host Interaction Signals for Virome Studies.}, journal = {Genomics, proteomics &amp; bioinformatics}, volume = {20}, number = {3}, pages = {508-523}, pmid = {35272051}, issn = {2210-3244}, mesh = {Humans ; *Bacteriophages/genetics ; Virome ; Prophages/genetics ; Bacteria/genetics ; *Microbiota ; }, abstract = {Phage-microbe interactions are appealing systems to study coevolution, and have also been increasingly emphasized due to their roles in human health, disease, and the development of novel therapeutics. Phage-microbe interactions leave diverse signals in bacterial and phage genomic sequences, defined as phage-host interaction signals (PHISs), which include clustered regularly interspaced short palindromic repeats (CRISPR) targeting, prophage, and protein-protein interaction signals. In the present study, we developed a novel tool phage-host interaction signal detector (PHISDetector) to predict phage-host interactions by detecting and integrating diverse in silico PHISs, and scoring the probability of phage-host interactions using machine learning models based on PHIS features. We evaluated the performance of PHISDetector on multiple benchmark datasets and application cases. When tested on a dataset of 758 annotated phage-host pairs, PHISDetector yields the prediction accuracies of 0.51 and 0.73 at the species and genus levels, respectively, outperforming other phage-host prediction tools. When applied to on 125,842 metagenomic viral contigs (mVCs) derived from 3042 geographically diverse samples, a detection rate of 54.54% could be achieved. Furthermore, PHISDetector could predict infecting phages for 85.6% of 368 multidrug-resistant (MDR) bacteria and 30% of 454 human gut bacteria obtained from the National Institutes of Health (NIH) Human Microbiome Project (HMP). The PHISDetector can be run either as a web server (http://www.microbiome-bigdata.com/PHISDetector/) for general users to study individual inputs or as a stand-alone version (https://github.com/HIT-ImmunologyLab/PHISDetector) to process massive phage contigs from virome studies.}, }
@article {pmid35271353, year = {2022}, author = {Fobofou, SA and Savidge, T}, title = {Microbial metabolites: cause or consequence in gastrointestinal disease?.}, journal = {American journal of physiology. Gastrointestinal and liver physiology}, volume = {322}, number = {6}, pages = {G535-G552}, pmid = {35271353}, issn = {1522-1547}, support = {R01 NR013497/NR/NINR NIH HHS/United States ; P30 DK056338/DK/NIDDK NIH HHS/United States ; R01 DK130517/DK/NIDDK NIH HHS/United States ; P01 AI152999/AI/NIAID NIH HHS/United States ; U01 AI124290/AI/NIAID NIH HHS/United States ; }, mesh = {*COVID-19 ; Dysbiosis/microbiology ; *Gastrointestinal Diseases ; *Gastrointestinal Microbiome ; Humans ; *Microbiota ; }, abstract = {Systems biology studies have established that changes in gastrointestinal microbiome composition and function can adversely impact host physiology. Notable diseases synonymously associated with dysbiosis include inflammatory bowel diseases, cancer, metabolic disorders, and opportunistic and recurrent pathogen infections. However, there is a scarcity of mechanistic data that advances our understanding of taxonomic correlations with pathophysiological host-microbiome interactions. Generally, to survive a hostile gut environment, microbes are highly metabolically active and produce trans-kingdom signaling molecules to interact with competing microorganisms and the host. These specialized metabolites likely play important homeostatic roles, and identifying disease-specific taxa and their effector pathways can provide better strategies for diagnosis, treatment, and prevention, as well as the discovery of innovative therapeutics. The signaling role of microbial biotransformation products such as bile acids, short-chain fatty acids, polysaccharides, and dietary tryptophan is increasingly recognized, but little is known about the identity and function of metabolites that are synthesized by microbial biosynthetic gene clusters, including ribosomally synthesized and posttranslationally modified peptides (RiPPs), nonribosomal peptides (NRPs), polyketides (PKs), PK-NRP hybrids, and terpenes. Here we consider how bioactive natural products directly encoded by the human microbiome can contribute to the pathophysiology of gastrointestinal disease, cancer, autoimmune, antimicrobial-resistant bacterial and viral infections (including COVID-19). We also present strategies used to discover these compounds and the biological activities they exhibit, with consideration of therapeutic interventions that could emerge from understanding molecular causation in gut microbiome research.}, }
@article {pmid35266930, year = {2022}, author = {Kynkäänniemi, E and Lahtinen, MH and Jian, C and Salonen, A and Hatanpää, T and Mikkonen, KS and Pajari, AM}, title = {Gut microbiota can utilize prebiotic birch glucuronoxylan in production of short-chain fatty acids in rats.}, journal = {Food &amp; function}, volume = {13}, number = {6}, pages = {3746-3759}, doi = {10.1039/d1fo03922a}, pmid = {35266930}, issn = {2042-650X}, mesh = {Animals ; Betula/metabolism ; Fatty Acids, Volatile/metabolism ; Female ; *Gastrointestinal Microbiome ; Male ; Prebiotics ; Rats ; Rats, Wistar ; Xylans ; }, abstract = {Birch-derived glucuronoxylan (GX)-rich hemicellulose extract is an abundantly available by-product of the forest industry. It has multifunctional food stabilizing properties, and is rich in fiber and polyphenols. Here, we studied its effects on colonic metabolism and gut microbiota in healthy rats. Male and female Wistar rats (n = 42) were fed AIN-93G-based diets with 10% (w/w) of either cellulose (control), a polyphenol and GX-rich extract (GXpoly), or a highly purified GX-rich extract (pureGX) for four weeks. Both the GXpoly and pureGX diets resulted in changes on the gut microbiota, especially in a higher abundance of Bifidobacteriaceae than the cellulose containing diet (p < 0.001). This coincided with higher concentrations of microbial metabolites in the luminal contents of the GX-fed than control rats, such as total short-chain fatty acids (SCFAs) (p < 0.001), acetate (p < 0.001), and N-nitroso compounds (NOCs) (p = 0.001). The difference in the concentration of NOCs was not seen when adjusted with fecal weight. GX supplementation supported the normal growth of the rats. Our results indicate that GXpoly and pureGX can favorably affect colonic metabolism and the gut microbiota. They have high potential to be used as prebiotic stabilizers to support more ecologically sustainable food production.}, }
@article {pmid35264784, year = {2022}, author = {Blaak, EE and de Vos, WM}, title = {Author Correction: Before the heart attack.}, journal = {Nature medicine}, volume = {28}, number = {4}, pages = {871}, doi = {10.1038/s41591-022-01764-9}, pmid = {35264784}, issn = {1546-170X}, }
@article {pmid35259160, year = {2022}, author = {Kieser, S and Zdobnov, EM and Trajkovski, M}, title = {Comprehensive mouse microbiota genome catalog reveals major difference to its human counterpart.}, journal = {PLoS computational biology}, volume = {18}, number = {3}, pages = {e1009947}, pmid = {35259160}, issn = {1553-7358}, mesh = {Animals ; Bacteria/genetics ; *Gastrointestinal Microbiome/genetics ; Humans ; Metagenome/genetics ; Metagenomics ; Mice ; *Microbiota/genetics ; Phylogeny ; }, abstract = {Mouse is the most used model for studying the impact of microbiota on its host, but the repertoire of species from the mouse gut microbiome remains largely unknown. Accordingly, the similarity between human and mouse microbiomes at a low taxonomic level is not clear. We construct a comprehensive mouse microbiota genome (CMMG) catalog by assembling all currently available mouse gut metagenomes and combining them with published reference and metagenome-assembled genomes. The 41'798 genomes cluster into 1'573 species, of which 78.1% are uncultured, and we discovered 226 new genera, seven new families, and one new order. CMMG enables an unprecedented coverage of the mouse gut microbiome exceeding 86%, increases the mapping rate over four-fold, and allows functional microbiota analyses of human and mouse linking them to the driver species. Comparing CMMG to microbiota from the unified human gastrointestinal genomes shows an overlap of 62% at the genus but only 10% at the species level, demonstrating that human and mouse gut microbiota are largely distinct. CMMG contains the most comprehensive collection of consistently functionally annotated species of the mouse and human microbiome to date, setting the ground for analysis of new and reanalysis of existing datasets at an unprecedented depth.}, }
@article {pmid35258340, year = {2022}, author = {Modha, S and Robertson, DL and Hughes, J and Orton, RJ}, title = {Quantifying and Cataloguing Unknown Sequences within Human Microbiomes.}, journal = {mSystems}, volume = {7}, number = {2}, pages = {e0146821}, pmid = {35258340}, issn = {2379-5077}, support = {MC_UU_12014/12/MRC_/Medical Research Council/United Kingdom ; MR/S502479/1//UKRI | Medical Research Council (MRC)/ ; MC_UU_1201412//UKRI | Medical Research Council (MRC)/ ; }, mesh = {Animals ; Humans ; *Ursidae/genetics ; *Microbiota/genetics ; Metagenome ; Metagenomics ; Databases, Factual ; }, abstract = {Advances in genome sequencing technologies and lower costs have enabled the exploration of a multitude of known and novel environments and microbiomes. This has led to an exponential growth in the raw sequence data that are deposited in online repositories. Metagenomic and metatranscriptomic data sets are typically analysed with regard to a specific biological question. However, it is widely acknowledged that these data sets are comprised of a proportion of sequences that bear no similarity to any currently known biological sequence, and this so-called "dark matter" is often excluded from downstream analyses. In this study, a systematic framework was developed to assemble, identify, and measure the proportion of unknown sequences present in distinct human microbiomes. This framework was applied to 40 distinct studies, comprising 963 samples, and covering 10 different human microbiomes including fecal, oral, lung, skin, and circulatory system microbiomes. We found that while the human microbiome is one of the most extensively studied, on average 2% of assembled sequences have not yet been taxonomically defined. However, this proportion varied extensively among different microbiomes and was as high as 25% for skin and oral microbiomes that have more interactions with the environment. A rate of taxonomic characterization of 1.64% of unknown sequences being characterized per month was calculated from these taxonomically unknown sequences discovered in this study. A cross-study comparison led to the identification of similar unknown sequences in different samples and/or microbiomes. Both our computational framework and the novel unknown sequences produced are publicly available for future cross-referencing. Our approach led to the discovery of several novel viral genomes that bear no similarity to sequences in the public databases. Some of these are widespread as they have been found in different microbiomes and studies. Hence, our study illustrates how the systematic characterization of unknown sequences can help the discovery of novel microbes, and we call on the research community to systematically collate and share the unknown sequences from metagenomic studies to increase the rate at which the unknown sequence space can be classified.}, }
@article {pmid35254118, year = {2022}, author = {Hao, Z and Zhu, Y and Fu, Y and Yang, J and Meng, C and Dong, C and Liu, H}, title = {Effects of Long-Term Enclosed Environment on Human Health Based on the Analysis of Salivary Microbiota and Cytokines.}, journal = {Microbiology spectrum}, volume = {10}, number = {2}, pages = {e0025422}, pmid = {35254118}, issn = {2165-0497}, mesh = {Cytokines ; Humans ; Life Support Systems ; *Microbiota ; Saliva ; *Space Flight ; }, abstract = {The long-term exposure to enclosed environments may lead to chronic stress in crewmembers and affect their physical and mental state. Salivary microbiome and biomarkers of immune function are increasingly used in human health research. The "Lunar Palace 365" project, which was a 370-day, multicrew, enclosed experiment carried out in a ground-based bioregenerative life support system platform named Lunar Palace 1 (LP1). We investigated the temporal dynamics of the salivary microbiota and cytokines in the third phase of the "Lunar Palace 365" experiment, including 1 month before entering LP1 and 1 month after leaving Lp1. Results reveal no regular temporal change pattern in these parameters (highly abundant phyla and genera) during the experiment. Although the crewmembers' oral microbiota temporally changed, it recovered quickly after the study subjects left the enclosed environment. The levels of IL-6, IL-10, and TNF-α in crewmembers' saliva decreased after leaving the normal environment for the enclosed environment, indicating that their oral inflammatory response level was reduced. There were significant individual differences in crewmembers' salivary microbiota, however, the shared living space reduced these differences. Moreover, air microbiota might have also played a significant role in reducing the individual differences. In summary, the enclosed environment did not result in persistent changes in human salivary microbiota and oral immunity. This study provides some insights for studying the effect of enclosed controlled environments on human immunity and microbiome. IMPORTANCE Long-term exposure to space environments may influence the human microbiome, the human immune system, and the intricate balance between the two, causing impaired immunity and increased disease susceptibility. It was previously believed that the main potential factors of long-term spaceflight on human health were microgravity and radiation. However, the effects of long-term enclosed environments on human health were unclear. Bioregenerative life support systems (BLSS) is a good experimental model for studying the effects of enclosed environments on human systemic microbiota and immune disorders. We monitored the microbiota and cytokines in the saliva of crewmembers before they entered BLSS, during their stay in BLSS, and after leaving BLSS. The results indicated long-term closed environment will not cause persistent changes in human salivary microbiota and immunity.}, }
@article {pmid35253754, year = {2022}, author = {Kalecký, K and German, DC and Montillo, AA and Bottiglieri, T}, title = {Targeted Metabolomic Analysis in Alzheimer's Disease Plasma and Brain Tissue in Non-Hispanic Whites.}, journal = {Journal of Alzheimer's disease : JAD}, volume = {86}, number = {4}, pages = {1875-1895}, pmid = {35253754}, issn = {1875-8908}, support = {P30 AG019610/AG/NIA NIH HHS/United States ; }, mesh = {*Alzheimer Disease/metabolism ; Brain/metabolism ; Case-Control Studies ; Female ; Humans ; Metabolome ; Tandem Mass Spectrometry ; }, abstract = {BACKGROUND: Metabolites are biological compounds reflecting the functional activity of organs and tissues. Understanding metabolic changes in Alzheimer's disease (AD) can provide insight into potential risk factors in this multifactorial disease and suggest new intervention strategies or improve non-invasive diagnosis.<br><br>OBJECTIVE: In this study, we searched for changes in AD metabolism in plasma and frontal brain cortex tissue samples and evaluated the performance of plasma measurements as biomarkers.<br><br>METHODS: This is a case-control study with two tissue cohorts: 158 plasma samples (94 AD, 64 controls; Texas Alzheimer's Research and Care Consortium - TARCC) and 71 postmortem cortex samples (35 AD, 36 controls; Banner Sun Health Research Institute brain bank). We performed targeted mass spectrometry analysis of 630 compounds (106 small molecules: UHPLC-MS/MS, 524 lipids: FIA-MS/MS) and 232 calculated metabolic indicators with a metabolomic kit (Biocrates MxP&#xae; Quant 500).<br><br>RESULTS: We discovered disturbances (FDR&#x2264;0.05) in multiple metabolic pathways in AD in both cohorts including microbiome-related metabolites with pro-toxic changes, methylhistidine metabolism, polyamines, corticosteroids, omega-3 fatty acids, acylcarnitines, ceramides, and diglycerides. In AD, plasma reveals elevated triglycerides, and cortex shows altered amino acid metabolism. A cross-validated diagnostic prediction model from plasma achieves AUC&#x200a;=&#x200a;82% (CI95&#x200a;=&#x200a;75-88%); for females specifically, AUC&#x200a;=&#x200a;88% (CI95&#x200a;=&#x200a;80-95%). A reduced model using 20 features achieves AUC&#x200a;=&#x200a;79% (CI95&#x200a;=&#x200a;71-85%); for females AUC&#x200a;=&#x200a;84% (CI95&#x200a;=&#x200a;74-92%).<br><br>CONCLUSION: Our findings support the involvement of gut environment in AD and encourage targeting multiple metabolic areas in the design of intervention strategies, including microbiome composition, hormonal balance, nutrients, and muscle homeostasis.}, }
@article {pmid35249149, year = {2022}, author = {Rietjens, IMCM and Michael, A and Bolt, HM and Siméon, B and Andrea, H and Nils, H and Christine, K and Angela, M and Gloria, P and Daniel, R and Natalie, T and Gerhard, E}, title = {The role of endogenous versus exogenous sources in the exposome of putative genotoxins and consequences for risk assessment.}, journal = {Archives of toxicology}, volume = {96}, number = {5}, pages = {1297-1352}, pmid = {35249149}, issn = {1432-0738}, mesh = {Acrolein ; *Exposome ; Formaldehyde ; Humans ; Mutagens/toxicity ; Risk Assessment ; }, abstract = {The "totality" of the human exposure is conceived to encompass life-associated endogenous and exogenous aggregate exposures. Process-related contaminants (PRCs) are not only formed in foods by heat processing, but also occur endogenously in the organism as physiological components of energy metabolism, potentially also generated by the human microbiome. To arrive at a comprehensive risk assessment, it is necessary to understand the contribution of in vivo background occurrence as compared to the ingestion from exogenous sources. Hence, this review provides an overview of the knowledge on the contribution of endogenous exposure to the overall exposure to putative genotoxic food contaminants, namely ethanol, acetaldehyde, formaldehyde, acrylamide, acrolein, α,β-unsaturated alkenals, glycation compounds, N-nitroso compounds, ethylene oxide, furans, 2- and 3-MCPD, and glycidyl esters. The evidence discussed herein allows to conclude that endogenous formation of some contaminants appears to contribute substantially to the exposome. This is of critical importance for risk assessment in the cases where endogenous exposure is suspected to outweigh the exogenous one (e.g. formaldehyde and acrolein).}, }
@article {pmid35242744, year = {2022}, author = {Wodzanowski, KA and Caplan, JL and Kloxin, AM and Grimes, CL}, title = {Multiscale Invasion Assay for Probing Macrophage Response to Gram-Negative Bacteria.}, journal = {Frontiers in chemistry}, volume = {10}, number = {}, pages = {842602}, pmid = {35242744}, issn = {2296-2646}, support = {DP2 HL152424/HL/NHLBI NIH HHS/United States ; P20 GM103446/GM/NIGMS NIH HHS/United States ; P20 GM104316/GM/NIGMS NIH HHS/United States ; P30 GM110758/GM/NIGMS NIH HHS/United States ; }, abstract = {The immune system is a complex network of various cellular components that must differentiate between pathogenic bacteria and the commensal bacteria of the human microbiome, where misrecognition is linked to inflammatory disorders. Fragments of bacterial cell wall peptidoglycan bind to pattern recognition receptors within macrophages, leading to immune activation. To study this complex process, a methodology to remodel and label the bacterial cell wall of two different species of bacteria was established using copper (I) catalyzed azide-alkyne cycloaddition (CuAAC) and strain-promoted azide-alkyne cycloaddition (SPAAC). Additionally, an approach for three-dimensional (3D) culture of human macrophages and their invasion with relevant bacteria in a well-defined hydrogel-based synthetic matrix inspired by the microenvironment of the gut was established. Workflows were developed for human monocyte encapsulation and differentiation into macrophages in 3D culture with high viability. Bacteria invaded into macrophages permitted in situ peptidoglycan labeling. Macrophages exhibited biologically-relevant cytokine release in response to bacteria. This molecularly engineered, multi-dimensional bacteria-macrophage co-culture system will prove useful in future studies to observe immunostimulatory, bacterial fragment production and localization in the cell at the carbohydrate level for insights into how the immune system properly senses bacteria.}, }
@article {pmid35242322, year = {2022}, author = {Sammoni, A and Abdalah, A and Al-Aissami, M}, title = {Comamonas testosteroni bacteremia: A rare unusual pathogen detected in a burned patient: Case report and literature review.}, journal = {Annals of medicine and surgery (2012)}, volume = {75}, number = {}, pages = {103371}, pmid = {35242322}, issn = {2049-0801}, abstract = {INTRODUCTION AND IMPORTANCE: Comamonas testosteroni is a rare human pathogen that is not part of the human microbiome. There are only 51 cases reported worldwide with 7 cases resulted in death.<br><br>CASE PRESENTATION: We report a case of a 16-year-old boy with an extended burn complicated by catheter-related bloodstream C. testosteroni infection.<br><br>CLINICAL DISCUSSION: Comamonas species are usually community-acquired pathogens that are susceptible to a wide variety of antibiotics including aminoglycosides, fluoroquinolones, carbapenems, piperacillin-tazobactam, trimethoprim-sulfamethoxazole, and cephalosporins. However, in our case, we reported a nosocomial multidrug-resistant infection by C. testosteroni that responded only to colistin.<br><br>CONCLUSION: Reporting unusual cases of nosocomial sepsis due to rare multidrug-resistant pathogens is detrimental. As it sheds light on how virulent nosocomial infections are becoming, and can be very alarming to other practitioners and clinical microbiologists, in order to achieve a better awareness of the importance of controlled antibiotics use.}, }
@article {pmid35236930, year = {2022}, author = {Hofer, U}, title = {Skewed representation in human microbiome data.}, journal = {Nature reviews. Microbiology}, volume = {20}, number = {5}, pages = {253}, pmid = {35236930}, issn = {1740-1534}, mesh = {*Gastrointestinal Microbiome ; Humans ; *Microbiota ; }, }
@article {pmid35234907, year = {2022}, author = {Kajova, M and Khawaja, T and Kantele, A}, title = {European hospitals as source of multidrug-resistant bacteria: analysis of travellers screened in Finland after hospitalization abroad.}, journal = {Journal of travel medicine}, volume = {29}, number = {4}, pages = {}, pmid = {35234907}, issn = {1708-8305}, mesh = {Anti-Bacterial Agents/pharmacology/therapeutic use ; Bacteria ; Drug Resistance, Multiple, Bacterial ; Escherichia coli ; Finland/epidemiology ; Hospitalization ; Hospitals ; Humans ; *Methicillin-Resistant Staphylococcus aureus ; Prevalence ; *Vancomycin-Resistant Enterococci ; }, abstract = {BACKGROUND: As hospitals have a high prevalence of multidrug-resistant organisms (MDRO), hospitalization abroad indicates for travellers an increased risk of acquiring MDRO-and carrying the strains home. Antimicrobial resistance (AMR) rates are highest in the (sub)tropics, whereas Europe is considered a lower risk region. Since AMR prevalences vary within Europe, we aimed to gather country-specific data on the risks for hospitalized travellers.<br><br>METHODS: At hospitals of the Helsinki and Uusimaa district in Finland, patients hospitalized abroad over the past 12&#xa0;months are systematically screened for methicillin-resistant Staphylococcus aureus (MRSA), extended-spectrum beta-lactamase (ESBL)-producing Enterobacterales (ESBL-PE), carbapenemase-producing bacteria and vancomycin-resistant Enterococcus spp. (VRE). Among patients screened 2010-19, we selected those hospitalized in Europe, recorded their MDRO findings, infections and mortality, and analysed MDRO-associated risk factors.<br><br>RESULTS: Of the 1772 patients treated in 41 European countries, 16.6% (295) carried MDRO, 12.5% (221) ESBL-PE, 7.8% (138) solely ESBL-E. coli, 2.6% (46) MRSA, 2.2% (30) of those screened VRE and 2.2% (39) carbapenem-resistant Gram-negatives. Among those colonized, 9.8% (29) had symptomatic MDRO infections and 0.3% (one) died. Colonization was most frequently recorded for those treated in eastern and southern Europe, with Bulgaria, Cyprus and the Russian Federation scoring highest. MDRO colonization was associated with antibiotic treatment and showed a negative correlation with time from discharge to screening.<br><br>CONCLUSIONS: After hospitalization in European countries, ESBL-PE carriage was relatively common (12.5%), while other MDROs proved less frequent (<5%). Antibiotic treatment and short time since hospitalization abroad increased the risk of MDRO colonization. Clear differences between countries and regions were revealed, with highest rates in the east and the south.}, }
@article {pmid35234490, year = {2022}, author = {Tourlousse, DM and Narita, K and Miura, T and Ohashi, A and Matsuda, M and Ohyama, Y and Shimamura, M and Furukawa, M and Kasahara, K and Kameyama, K and Saito, S and Goto, M and Shimizu, R and Mishima, R and Nakayama, J and Hosomi, K and Kunisawa, J and Terauchi, J and Sekiguchi, Y and Kawasaki, H}, title = {Characterization and Demonstration of Mock Communities as Control Reagents for Accurate Human Microbiome Community Measurements.}, journal = {Microbiology spectrum}, volume = {10}, number = {2}, pages = {e0191521}, pmid = {35234490}, issn = {2165-0497}, mesh = {DNA ; High-Throughput Nucleotide Sequencing/methods ; Humans ; Indicators and Reagents ; Metagenomics/methods ; *Microbiota/genetics ; RNA, Ribosomal, 16S/genetics ; Reproducibility of Results ; Sequence Analysis, DNA/methods ; }, abstract = {Standardization and quality assurance of microbiome community analysis by high-throughput DNA sequencing require widely accessible and well-characterized reference materials. Here, we report on newly developed DNA and whole-cell mock communities to serve as control reagents for human gut microbiota measurements by shotgun metagenomics and 16S rRNA gene amplicon sequencing. The mock communities were formulated as near-even blends of up to 20 bacterial species prevalent in the human gut, span a wide range of genomic guanine-cytosine (GC) contents, and include multiple strains with Gram-positive type cell walls. Through a collaborative study, we carefully characterized the mock communities by shotgun metagenomics, using previously developed standardized protocols for DNA extraction and sequencing library construction. Further, we validated fitness of the mock communities for revealing technically meaningful differences among protocols for DNA extraction and metagenome/16S rRNA gene amplicon library construction. Finally, we used the mock communities to reveal varying performance of metagenome-based taxonomic profilers and the impact of trimming and filtering of sequencing reads on observed species profiles. The latter showed that aggressive preprocessing of reads may result in substantial GC-dependent bias and should thus be carefully evaluated to minimize unintended effects on species abundances. Taken together, the mock communities are expected to support a myriad of applications that rely on well-characterized control reagents, ranging from evaluation and optimization of methods to assessment of reproducibility in interlaboratory studies and routine quality control. IMPORTANCE Application of high-throughput DNA sequencing has greatly accelerated human microbiome research and its translation into new therapeutic and diagnostic capabilities. Microbiome community analyses results can, however, vary considerably across studies or laboratories, and establishment of measurement standards to improve accuracy and reproducibility has become a priority. The here-developed mock communities, which are available from the NITE Biological Resource Center (NBRC) at the National Institute of Technology and Evaluation (NITE, Japan), provide well-characterized control reagents that allow users to judge the accuracy of their measurement results. Widespread and consistent adoption of the mock communities will improve reproducibility and comparability of microbiome community analyses, thereby supporting and accelerating human microbiome research and development.}, }
@article {pmid35222791, year = {2022}, author = {Beghelli, D and Zallocco, L and Barbalace, MC and Paglia, S and Strocchi, S and Cirilli, I and Marzano, V and Putignani, L and Lupidi, G and Hrelia, S and Giusti, L and Angeloni, C}, title = {Pterostilbene Promotes Mean Lifespan in Both Male and Female Drosophila Melanogaster Modulating Different Proteins in the Two Sexes.}, journal = {Oxidative medicine and cellular longevity}, volume = {2022}, number = {}, pages = {1744408}, pmid = {35222791}, issn = {1942-0994}, mesh = {Animals ; Anti-Inflammatory Agents/metabolism ; Antioxidants/metabolism ; Drosophila Proteins/genetics/metabolism ; Drosophila melanogaster ; Female ; Longevity/*drug effects/genetics ; Male ; Oxidative Stress/drug effects ; Proteome/drug effects/metabolism ; Sex Factors ; Stilbenes/*pharmacology ; }, abstract = {Aging is a multifactorial phenomenon characterized by degenerative processes closely connected to oxidative damage and chronic inflammation. Recently, many studies have shown that natural bioactive compounds are useful in delaying the aging process. In this work, we studied the effects of an in vivo supplementation of the stilbenoid pterostilbene on lifespan extension in Drosophila melanogaster. We found that the average lifespan of flies of both sexes was increased by pterostilbene supplementation with a higher effect in females. The expression of longevity related genes (Sir2, Foxo, and Notch) was increased in both sexes but with different patterns. Pterostilbene counteracted oxidative stress induced by ethanol and paraquat and up-regulated the antioxidant enzymes Ho e Trxr-1 in male but not in female flies. On the other hand, pterostilbene decreased the inflammatory mediators dome and egr only in female flies. Proteomic analysis revealed that pterostilbene modulates 113 proteins in male flies and only 9 in females. Only one of these proteins was modulated by pterostilbene in both sexes: vacuolar H[+] ATPase 68 kDa subunit 2 (Vha68-2) that was strongly down-regulated. These findings suggest a potential role of pterostilbene in increasing lifespan both in male and female flies by mechanisms that seem to be different in the two sexes, highlighting the need to conduct nutraceutical supplementation studies on males and females separately in order to give more reliable results.}, }
@article {pmid35216302, year = {2022}, author = {Shi, Y and Wang, G and Lau, HC and Yu, J}, title = {Metagenomic Sequencing for Microbial DNA in Human Samples: Emerging Technological Advances.}, journal = {International journal of molecular sciences}, volume = {23}, number = {4}, pages = {}, pmid = {35216302}, issn = {1422-0067}, support = {2020YFA0509200/2020YFA0509203//National Key R&amp;D Program of China/ ; T21-705/20-N//RGC Theme-based Res Scheme Hong Kong/ ; C4039-19GF, C7065-18GF//RGC Collaborative Research Fund/ ; 14163817//RGC-GRF Hong Kong/ ; Vice-Chancellor's Discretionary Fund//Chinese University of Hong Kong/ ; }, mesh = {DNA/genetics ; *High-Throughput Nucleotide Sequencing/methods ; Humans ; Metagenome ; *Metagenomics/methods ; Sequence Analysis, DNA/methods ; Technology ; }, abstract = {Whole genome metagenomic sequencing is a powerful platform enabling the simultaneous identification of all genes from entirely different kingdoms of organisms in a complex sample. This technology has revolutionised multiple areas from microbiome research to clinical diagnoses. However, one of the major challenges of a metagenomic study is the overwhelming non-microbial DNA present in most of the host-derived specimens, which can inundate the microbial signals and reduce the sensitivity of microorganism detection. Various host DNA depletion methods to facilitate metagenomic sequencing have been developed and have received considerable attention in this context. In this review, we present an overview of current host DNA depletion approaches along with explanations of their underlying principles, advantages and disadvantages. We also discuss their applications in laboratory microbiome research and clinical diagnoses and, finally, we envisage the direction of the further perfection of metagenomic sequencing in samples with overabundant host DNA.}, }
@article {pmid35215830, year = {2022}, author = {Skurnik, M}, title = {Editorial of Viruses Special Issue on Phage-Host Interactions 2021.}, journal = {Viruses}, volume = {14}, number = {2}, pages = {}, doi = {10.3390/v14020236}, pmid = {35215830}, issn = {1999-4915}, mesh = {Bacteria/*virology ; Bacteriophages/genetics/*physiology ; *Host Microbial Interactions ; Host Specificity ; }, abstract = {Viruses has now published two Special Issues on phage-host interactions, the latest under the name Phage-Host Interactions 2021 [...].}, }
@article {pmid35212478, year = {2022}, author = {Patangia, DV and Anthony Ryan, C and Dempsey, E and Paul Ross, R and Stanton, C}, title = {Impact of antibiotics on the human microbiome and consequences for host health.}, journal = {MicrobiologyOpen}, volume = {11}, number = {1}, pages = {e1260}, pmid = {35212478}, issn = {2045-8827}, mesh = {Adult ; Animals ; Anti-Bacterial Agents/administration &amp; dosage/*pharmacology ; Child ; Female ; Humans ; Infant ; Infant, Newborn ; Microbiota/*drug effects ; Pregnancy ; }, abstract = {It is well established that the gut microbiota plays an important role in host health and is perturbed by several factors including antibiotics. Antibiotic-induced changes in microbial composition can have a negative impact on host health including reduced microbial diversity, changes in functional attributes of the microbiota, formation, and selection of antibiotic-resistant strains making hosts more susceptible to infection with pathogens such as Clostridioides difficile. Antibiotic resistance is a global crisis and the increased use of antibiotics over time warrants investigation into its effects on microbiota and health. In this review, we discuss the adverse effects of antibiotics on the gut microbiota and thus host health, and suggest alternative approaches to antibiotic use.}, }
@article {pmid35208921, year = {2022}, author = {Reddel, S and Pascucci, GR and Foligno, S and Del Chierico, F and Vernocchi, P and Marzullo, A and Pattumelli, MG and Palma, P and Salvatori, G and Putignani, L}, title = {A Parallel Tracking of Salivary and Gut Microbiota Profiles Can Reveal Maturation and Interplay of Early Life Microbial Communities in Healthy Infants.}, journal = {Microorganisms}, volume = {10}, number = {2}, pages = {}, pmid = {35208921}, issn = {2076-2607}, support = {Ricerca Corrente 2016, 2017, 778 2018, 2019 and 5 &#x2030; 2020//Italian Ministry of Health/ ; 201903_DICOFARM//DICOFARM/ ; }, abstract = {In this study, the onset and shaping of the salivary and gut microbiota in healthy newborns during the first period of life has been followed, evaluating the impact of salivary microbiota on the development of early fecal microbial communities. The microbiota of 80 salivary and 82 fecal samples that were collected from healthy newborns in the first six months of life, was investigated by 16S rRNA amplicon profiling. The microbial relationship within and between the saliva and gut ecosystems was determined by correlation heatmaps and co-occurrence networks. Streptococcus and Staphylococcus appeared as early commensals in the salivary microbiota, dominating this ecosystem through the time, while Fusobacterium, Prevotella, Porphyromonas, Granulicatella, and Veillonella were late colonizers. Enterobacteriaceae, Staphylococcus and Streptococcus were gut pioneers, followed by the anaerobic Bifidobacterium, Veillonella, Eggerthella, and Bacteroides. Streptococcus, Staphylococcus, and Veillonella were shared by the gut and saliva ecosystems. The saliva and gut microbiota seem to evolve independently, driven by local adaptation strategies, except for the oral Streptococcus and Veillonella that are involved in gut microbiota development as seeding species. This study offers a piece of knowledge on how the oral microbiota may affect the gut microbiota in healthy newborns, shedding light onto new microbial targets for the development of therapies for early life intestinal dysbiosis.}, }
@article {pmid35208736, year = {2022}, author = {Stuivenberg, GA and Burton, JP and Bron, PA and Reid, G}, title = {Why Are Bifidobacteria Important for Infants?.}, journal = {Microorganisms}, volume = {10}, number = {2}, pages = {}, pmid = {35208736}, issn = {2076-2607}, support = {Unknown//Natural Sciences and Engineering Research Council/ ; }, abstract = {The presence of Bifidobacterium species in the maternal vaginal and fecal microbiota is arguably an evolutionary trait that allows these organisms to be primary colonizers of the newborn intestinal tract. Their ability to utilize human milk oligosaccharides fosters their establishment as core health-promoting organisms throughout life. A reduction in their abundance in infants has been shown to increase the prevalence of obesity, diabetes, metabolic disorder, and all-cause mortality later in life. Probiotic strains have been developed as supplements for premature babies and to counter some of these ailments as well as to confer a range of health benefits. The ability to modulate the immune response and produce short-chain fatty acids, particularly acetate and butyrate, that strengthen the gut barrier and regulate the gut microbiome, makes Bifidobacterium a core component of a healthy infant through adulthood.}, }
@article {pmid35208194, year = {2022}, author = {Yan, D and Cao, L and Zhou, M and Mohimani, H}, title = {TransDiscovery: Discovering Biotransformation from Human Microbiota by Integrating Metagenomic and Metabolomic Data.}, journal = {Metabolites}, volume = {12}, number = {2}, pages = {}, pmid = {35208194}, issn = {2218-1989}, support = {DP2 GM137413/GM/NIGMS NIH HHS/United States ; DP2GM137413//National Institute of Health/ ; }, abstract = {The human microbiome is a complex community of microorganisms, their enzymes, and the molecules they produce or modify. Recent studies show that imbalances in human microbial ecosystems can cause disease. Our microbiome affects our health through the products of biochemical reactions catalyzed by microbial enzymes (microbial biotransformations). Despite their significance, currently, there are no systematic strategies for identifying these chemical reactions, their substrates and molecular products, and their effects on health and disease. We present TransDiscovery, a computational algorithm that integrates molecular networks (connecting related molecules with similar mass spectra), association networks (connecting co-occurring molecules and microbes) and knowledge bases of microbial enzymes to discover microbial biotransformations, their substrates, and their products. After searching the metabolomics and metagenomics data from the American Gut Project and the Global Foodomic Project, TranDiscovery identified 17 potentially novel biotransformations from the human gut microbiome, along with the corresponding microbial species, substrates, and products.}, }
@article {pmid35204374, year = {2022}, author = {Bschleipfer, T and Karl, I}, title = {Bladder Microbiome in the Context of Urological Disorders-Is There a Biomarker Potential for Interstitial Cystitis?.}, journal = {Diagnostics (Basel, Switzerland)}, volume = {12}, number = {2}, pages = {}, pmid = {35204374}, issn = {2075-4418}, abstract = {Since the development of modern cultivation and sequencing techniques, the human microbiome has increasingly become the focus of scientific attention. Even in the bladder, long considered to be a sterile niche, a highly variable and complex microbial colonization has now been demonstrated. Especially in the context of diseases such as interstitial cystitis, whose etiopathogenesis is largely unknown, and whose diagnosis is based on a process of exclusion of confusable diseases, science hopes to gain far-reaching insights for etiology and diagnosis, including the identification of potential biomarkers. While for functional disorders such as urge urinary incontinence and overactive bladder syndrome, initial associations have been demonstrated between reduced microbial diversity and increased symptomatology, as well as shifts in the abundance of specific microorganisms such as Lactobacillus or Proteus, studies in interstitial cystitis show conflicting results and have failed to identify a putative organism or urotype that clearly distinguishes the urinary microbiome of patients with IC/BPS from that of healthy controls. At the present time, therefore, the new insights into the bladder microbiome and its potential influence on urologic disease cannot yet be used in the context of elucidating possible etiopathogenetic causes, as well as in the use of a biomarker for diagnostic or prognostic purposes. Further studies should focus primarily on uniform procedures and detection methods to achieve better comparability of results and increase the likelihood of detecting hidden patterns.}, }
@article {pmid35203519, year = {2022}, author = {Craciun, CI and Neag, MA and Catinean, A and Mitre, AO and Rusu, A and Bala, C and Roman, G and Buzoianu, AD and Muntean, DM and Craciun, AE}, title = {The Relationships between Gut Microbiota and Diabetes Mellitus, and Treatments for Diabetes Mellitus.}, journal = {Biomedicines}, volume = {10}, number = {2}, pages = {}, pmid = {35203519}, issn = {2227-9059}, abstract = {Diabetes mellitus is considered to be a global epidemic. The combination of genetic susceptibility and an unhealthy lifestyle is considered to be the main trigger of this metabolic disorder. Recently, there has been increased interest in the roles of gut microbiota as a new potential contributor to this epidemic. Research, in recent years, has contributed to an in-depth characterization of the human microbiome and its associations with various diseases, including metabolic diseases and diabetes mellitus. It is known that diet can change the composition of gut microbiota, but it is unclear how this, in turn, may influence metabolism. The main objective of this review is to evaluate the pathogenetic association between microbiota and diabetes and to explore any new therapeutic agents, including nutraceuticals that may modulate the microbiota. We also look at several mechanisms involved in this process. There is a clear, bidirectional relationship between microbiota and diabetes. Current treatments for diabetes influence microbiota in various ways, some beneficial, but others with still unclear effects. Microbiota-aimed treatments have seen no real-world significant effects on the progression of diabetes and its complications, with more studies needed in order to find a really beneficial agent.}, }
@article {pmid35202611, year = {2022}, author = {Jia, B and Kim, KH and Ruan, W and Kim, HM and Jeon, CO}, title = {Lantibiotic-encoding Streptococcus in the human microbiome are underlying risk factors for liver diseases.}, journal = {The Journal of infection}, volume = {84}, number = {5}, pages = {e70-e72}, doi = {10.1016/j.jinf.2022.02.020}, pmid = {35202611}, issn = {1532-2742}, mesh = {*Bacteriocins ; Humans ; Liver Cirrhosis ; *Liver Diseases ; *Microbiota ; Risk Factors ; Streptococcus ; }, }
@article {pmid35191218, year = {2022}, author = {Qu, D and Wang, Y and Xia, Q and Chang, J and Jiang, X and Zhang, H}, title = {Intratumoral Microbiome of Human Primary Liver Cancer.}, journal = {Hepatology communications}, volume = {6}, number = {7}, pages = {1741-1752}, pmid = {35191218}, issn = {2471-254X}, mesh = {Bacteria ; Humans ; Immunotherapy ; *Liver Neoplasms/therapy ; *Microbiota/genetics ; RNA, Ribosomal, 16S/genetics ; Tumor Microenvironment ; }, abstract = {Primary liver tumors (PLCs) and liver metastasis currently represent the leading cause of cancer-related deaths worldwide due to poor outcomes, high incidence, and postsurgical recurrence. Hence, novel diagnostic markers and therapeutic strategies for PLCs are urgently needed. The human microbiome can directly or indirectly impact cancer initiation, progression, and response to therapy, including cancer immunotherapy; however, the roles of the microbiota in the tumor microenvironment are not clear and require more investigation. Here, we investigated intratumoral microbial community profiling on formalin-fixed paraffin-embedded tissue samples of patients with PLC by 16S ribosomal RNA using the MiSeq platform. We characterized the microbial communities in different histopathological subtypes and in the different prognoses of patients with PLC. The study revealed microbial population differences not only in carcinoma tissue and the matched adjacent nontumor tissue but in different histopathological subtypes, even in patients with PLC with different prognoses. Interestingly, the abundance of certain bacteria that have antitumor effects at family and genus level, such as Pseudomonadaceae, decreased in tumor tissue and was linearly associated with prognosis of patients with PLC. Conclusion: We provide a potential novel diagnostic biomarker and therapeutic strategy for early clinical diagnosis and treatment of PLC.}, }
@article {pmid35190251, year = {2022}, author = {Moossavi, S and Arrieta, MC and Sanati-Nezhad, A and Bishehsari, F}, title = {Gut-on-chip for ecological and causal human gut microbiome research.}, journal = {Trends in microbiology}, volume = {30}, number = {8}, pages = {710-721}, doi = {10.1016/j.tim.2022.01.014}, pmid = {35190251}, issn = {1878-4380}, support = {//CIHR/Canada ; }, mesh = {Animals ; Diet ; *Gastrointestinal Microbiome/physiology ; Host Microbial Interactions ; Humans ; Mice ; *Microbiota ; }, abstract = {There is a growing interest to understand if and how the gut microbiome is causally linked to the pathogenesis and/or progression of diseases. While in vitro cell line models are commonly used for studying specific aspects of the host-microbe interaction, gnotobiotic murine models are considered the preferred platform for studying causality in microbiome research. Nevertheless, findings from animal studies provide limited opportunity for delineating various areas of interest to the human gut microbiome research. Gut-on-chips are biomimetics recapitulating intestinal physiology which enable investigation of bidirectional effects of the host and microbiome. We posit that they could advance causal and ecological gut microbiome research in three major areas: (i) diet-microbiome and drug-microbiome interaction; (ii) microbiome-targeted therapeutics pharmacoecology; and (iii) mechanistic studies of gut microbiome and microbiome-targeted intervention in extraintestinal pathologies.}, }
@article {pmid35186803, year = {2022}, author = {Manzanares-Leal, GL and Coronel-Martínez, JA and Rodríguez-Morales, M and Rangel-Cuevas, I and Bustamante-Montes, LP and Sandoval-Trujillo, H and Ramírez-Durán, N}, title = {Preliminary Identification of the Aerobic Cervicovaginal Microbiota in Mexican Women With Cervical Cancer as the First Step Towards Metagenomic Studies.}, journal = {Frontiers in cellular and infection microbiology}, volume = {12}, number = {}, pages = {838491}, pmid = {35186803}, issn = {2235-2988}, mesh = {Adult ; Aged ; Cross-Sectional Studies ; Female ; Humans ; *Microbiota/genetics ; Middle Aged ; Pregnancy ; RNA, Ribosomal, 16S/genetics ; *Uterine Cervical Neoplasms ; Vagina/microbiology ; Young Adult ; }, abstract = {Cervical cancer (CC) is considered a public health problem. Recent studies have evaluated the possible relationship between the cervicovaginal microbiome and gynecologic cancer but have not studied the relationship between aerobic bacterial communities and neoplasia. The study aimed to identify the cultivable aerobic bacterial microbiota in women with cervical cancer as a preliminary approach to the metagenomic study of the cervicovaginal microbiome associated with cervical cancer in Mexican women. An observational cross-sectional study was conducted, including 120 women aged 21-71 years, divided into two study groups, women with locally advanced CC (n=60) and women without CC (n=60). Sociodemographic, gynecological-obstetric, sexual, and habit data were collected. Cervicovaginal samples were collected by swabbing, from which standard microbiological methods obtained culturable bacteria. The strains were genetically characterized by PCR-RFLP of the 16S rRNA gene and subsequently identified by sequencing the same gene. Variables regularly reported as risk factors for the disease were found in women with CC. Differences were found in the prevalence and number of species isolated in each study group. Bacteria commonly reported in women with aerobic vaginitis were identified. There were 12 species in women with CC, mainly Corynebacterium spp. and Staphylococcus spp.; we found 13 bacterial species in the group without cancer, mainly Enterococcus spp. and Escherichia spp. The advanced stages presented a more significant number of isolates and species. This study provided a preliminary test for cervicovaginal metagenomic analysis, demonstrating the presence of aerobic cervicovaginal dysbiosis in women with CC and the need for more in-depth studies.}, }
@article {pmid35185849, year = {2022}, author = {Mousa, WK and Chehadeh, F and Husband, S}, title = {Recent Advances in Understanding the Structure and Function of the Human Microbiome.}, journal = {Frontiers in microbiology}, volume = {13}, number = {}, pages = {825338}, pmid = {35185849}, issn = {1664-302X}, abstract = {Trillions of microbes live within our bodies in a deep symbiotic relationship. Microbial populations vary across body sites, driven by differences in the environment, immunological factors, and interactions between microbial species. Major advances in genome sequencing enable a better understanding of microbiome composition. However, most of the microbial taxa and species of the human microbiome are still unknown. Without revealing the identity of these microbes as a first step, we cannot appreciate their role in human health and diseases. A shift in the microbial balance, termed dysbiosis, is linked to a broad range of diseases from simple colitis and indigestion to cancer and dementia. The last decade has witnessed an explosion in microbiome research that led to a better understanding of the microbiome structure and function. This understanding leads to potential opportunities to develop next-generation microbiome-based drugs and diagnostic biomarkers. However, our understanding is limited given the highly personalized nature of the microbiome and its complex and multidirectional interactions with the host. In this review, we discuss: (1) our current knowledge of microbiome structure and factors that shape the microbial composition, (2) recent associations between microbiome dysbiosis and diseases, and (3) opportunities of new microbiome-based therapeutics. We analyze common themes, promises, gaps, and challenges of the microbiome research.}, }
@article {pmid35182101, year = {2022}, author = {Dhakal, S and Moazzami, Z and Perry, C and Dey, M}, title = {Effects of Lean Pork on Microbiota and Microbial-Metabolite Trimethylamine-N-Oxide: A Randomized Controlled Non-Inferiority Feeding Trial Based on the Dietary Guidelines for Americans.}, journal = {Molecular nutrition &amp; food research}, volume = {66}, number = {9}, pages = {e2101136}, doi = {10.1002/mnfr.202101136}, pmid = {35182101}, issn = {1613-4133}, support = {U2C ES030158/ES/NIEHS NIH HHS/United States ; }, mesh = {Animals ; Choline/metabolism ; *Gastrointestinal Microbiome ; Humans ; Methylamines ; *Microbiota ; Nutrition Policy ; Oxides ; *Pork Meat ; Poultry/metabolism ; *Red Meat ; Swine ; }, abstract = {SCOPE: Trimethylamine-N-oxide (TMAO) is a microbiota-dependent and primarily animal-protein-derived proatherogenic metabolite. The ecological impact of pork-the most popular animal protein worldwide-on the human microbiome, and in the physiological context of TMAO and other biogenic amines, remains unknown. Poultry being the recommended heart-healthier animal protein, we investigated-if pork intake results in inferior-to-chicken TMAO-response while consuming a diet based on the Dietary Guidelines for Americans (DGA).<br><br>METHODS AND RESULTS: In a randomized, controlled, all-food-provided, crossover, feeding trial, healthy adults consumed 156&#xa0;g day[-1] of lean-pork or chicken (active-control) as primary proteins. Mixed-effect modeling shows pork as noninferior to chicken for circulating TMAO response and microbiota-generated essential TMAO-precursor-trimethylamine (97.5% CI, n = 36/protein). Markers of lipid metabolism, inflammation and oxidative stress, serum levels of betaine, choline, L-carnitine, composition and functional-capability of the microbiota, and association of baseline TMAO-levels with TMAO-response (both, r > 0.6, p = 0.0001) are nondistinguishable between the protein groups. TMAO reduction and similar shifts in microbiota and biogenic-amine signatures postdiet in both groups indicate a background DGA-effect.<br><br>CONCLUSION: Unlike extrapolating negative results, this study presents noninferiority-testing based evidence. Consuming pork as a predominant protein within an omnivorous DGA-diet does not exacerbate TMAO-response. Results highlight the importance of understanding protein-TMAO interactions within dietary patterns.}, }
@article {pmid35181661, year = {2022}, author = {Johansen, J and Plichta, DR and Nissen, JN and Jespersen, ML and Shah, SA and Deng, L and Stokholm, J and Bisgaard, H and Nielsen, DS and Sørensen, SJ and Rasmussen, S}, title = {Genome binning of viral entities from bulk metagenomics data.}, journal = {Nature communications}, volume = {13}, number = {1}, pages = {965}, pmid = {35181661}, issn = {2041-1723}, mesh = {Bacteriophages/*classification/genetics ; Gastrointestinal Microbiome/*genetics/physiology ; Gastrointestinal Tract/*virology ; Genome, Viral/genetics ; Humans ; Metagenome/*genetics ; Metagenomics ; Virome/*genetics/physiology ; }, abstract = {Despite the accelerating number of uncultivated virus sequences discovered in metagenomics and their apparent importance for health and disease, the human gut virome and its interactions with bacteria in the gastrointestinal tract are not well understood. This is partly due to a paucity of whole-virome datasets and limitations in current approaches for identifying viral sequences in metagenomics data. Here, combining a deep-learning based metagenomics binning algorithm with paired metagenome and metavirome datasets, we develop Phages from Metagenomics Binning (PHAMB), an approach that allows the binning of thousands of viral genomes directly from bulk metagenomics data, while simultaneously enabling clustering of viral genomes into accurate taxonomic viral populations. When applied on the Human Microbiome Project 2 (HMP2) dataset, PHAMB recovered 6,077 high-quality genomes from 1,024 viral populations, and identified viral-microbial host interactions. PHAMB can be advantageously applied to existing and future metagenomes to illuminate viral ecological dynamics with other microbiome constituents.}, }
@article {pmid35177861, year = {2022}, author = {Blaak, EE and de Vos, WM}, title = {Before the heart attack.}, journal = {Nature medicine}, volume = {28}, number = {2}, pages = {237-238}, pmid = {35177861}, issn = {1546-170X}, mesh = {*Coronary Artery Disease ; Humans ; *Microbiota ; *Myocardial Infarction ; Risk Factors ; }, }
@article {pmid35176353, year = {2022}, author = {Mandal, S and Bandyopadhyay, S and Tyagi, K and Roy, A}, title = {Human microbial dysbiosis as driver of gynecological malignancies.}, journal = {Biochimie}, volume = {197}, number = {}, pages = {86-95}, doi = {10.1016/j.biochi.2022.02.005}, pmid = {35176353}, issn = {1638-6183}, mesh = {Biomarkers ; Dysbiosis/microbiology ; Female ; *Genital Neoplasms, Female ; Humans ; Lactobacillus ; *Microbiota ; }, abstract = {Gynecological cancers that affect female reproductive tract, remain at the top of the global cancer burden list with high relapse rate and mortality. Notwithstanding development of several novel therapeutic interventions including poly-ADP-ribose polymerase inhibitors, this family of malignancies remain deadly. The human microbiome project demonstrated that dysbiosis of health resident microflora is associated with several pathologies including malignancies of the female reproductive tract and detailed characterization of species variation and host-microbe interaction could provide clues for identification of early diagnostic biomarker, preventive and therapeutic interventions. Emerging evidence suggests that several microbial signatures are significantly associated with gynecological cancers. An increased population of Proteobacteria and Firmicutes followed by significantly reduced Lactobacilli are associated with lethal epithelial ovarian cancer. Similarly, a constant association of elevated level of Atopobium vaginae, Porphyromonas somerae, Micrococci and Gardnerella vaginalis are observed in endometrial and cervical cancers. Moreover, human papilloma virus infection significantly augments colonization of pathogenic microbes including Sneathia sanguinegens, Anaerococcus tetradius, and Peptostreptococcus anaerobius and drives carcinoma of the cervix. Interestingly, microbial dysbiosis in female reproductive tract modulates expression of several microbial and immune-responsive genes such as TLR-4, TLR-5, TLR-6 and NOD-1. Therefore, stringent investigation into the microbial dysbiosis and its underlying mechanism could provide valuable cues for identification of early diagnostic biomarker, preventive and therapeutic interventions against rogue gynecological malignancies.}, }
@article {pmid35170866, year = {2022}, author = {Falduto, M and Smedile, F and Zhang, M and Zheng, T and Zhu, J and Huang, Q and Weeks, R and Ermakov, AM and Chikindas, ML}, title = {Anti-obesity effects of Chenpi: an artificial gastrointestinal system study.}, journal = {Microbial biotechnology}, volume = {15}, number = {3}, pages = {874-885}, pmid = {35170866}, issn = {1751-7915}, mesh = {Aged ; Clostridiales ; *Drugs, Chinese Herbal ; Emulsions ; Humans ; *Microbiota ; Obesity ; RNA, Ribosomal, 16S/genetics ; }, abstract = {The gut microbiota plays a significant role in human health; however, the complex relationship between gut microbial communities and host health is still to be thoroughly studied and understood. Microbes in the distal gut contribute to host health through the biosynthesis of vitamins and essential amino acids and the generation of important metabolic by-products from dietary components that are left undigested by the small intestine. Aged citrus peel (Chenpi) is used in traditional Chinese medicine to lower cholesterol, promote weight loss and treat various gastrointestinal symptoms. This study investigated how the microbial community changes during treatment with Chenpi using the Simulator of the Human Intestinal Microbial Ecosystem (SHIME). Two preparations of Chenpi extract were tested: Chenpi suspended in oil only and Chenpi in a viscoelastic emulsion. Short-chain fatty acids (SCFAs) were measured during treatment to monitor changes in the microbial community of the colon presenting a decrease in production for acetic, propionic and butyric acid (ANOVA (P < 0.001) during the 15 days of treatment. 16S rRNA sequencing of microbial samples showed a clear difference between the two treatments at the different sampling times (ANOSIM P < 0.003; ADOSIM P < 0.002 [R[2] = 69%]). Beta diversity analysis by PcoA showed differences between the two Chenpi formulations for treatment day 6. These differences were no longer detectable as soon as the Chenpi treatment was stopped, showing a reversible effect of Chenpi on the human microbiome. 16S rRNA sequencing of microbial samples from the descending colon showed an increase in Firmicutes for the treatment with the viscoelastic emulsion. At the genus level, Roseburia, Blautia, Subdoligranulum and Eubacterium increased in numbers during the viscoelastic emulsion treatment. This study sheds light on the anti-obesity effect of a polymethoxyflavone (PMFs)-enriched Chenpi extract and creates a foundation for the identification of 'obesity-prevention' biomarkers in the gut microbiota.}, }
@article {pmid35167588, year = {2022}, author = {Abdill, RJ and Adamowicz, EM and Blekhman, R}, title = {Public human microbiome data are dominated by highly developed countries.}, journal = {PLoS biology}, volume = {20}, number = {2}, pages = {e3001536}, pmid = {35167588}, issn = {1545-7885}, support = {R35 GM128716/GM/NIGMS NIH HHS/United States ; }, mesh = {Asia ; Bangladesh ; Canada ; Developed Countries ; Europe ; Gastrointestinal Microbiome/*genetics ; Genomics/*methods/statistics &amp; numerical data ; Geography ; Humans ; India ; Metagenome/*genetics ; Metagenomics/*methods/statistics &amp; numerical data ; Microbiota/*genetics ; Pakistan ; United States ; }, abstract = {The importance of sampling from globally representative populations has been well established in human genomics. In human microbiome research, however, we lack a full understanding of the global distribution of sampling in research studies. This information is crucial to better understand global patterns of microbiome-associated diseases and to extend the health benefits of this research to all populations. Here, we analyze the country of origin of all 444,829 human microbiome samples that are available from the world's 3 largest genomic data repositories, including the Sequence Read Archive (SRA). The samples are from 2,592 studies of 19 body sites, including 220,017 samples of the gut microbiome. We show that more than 71% of samples with a known origin come from Europe, the United States, and Canada, including 46.8% from the US alone, despite the country representing only 4.3% of the global population. We also find that central and southern Asia is the most underrepresented region: Countries such as India, Pakistan, and Bangladesh account for more than a quarter of the world population but make up only 1.8% of human microbiome samples. These results demonstrate a critical need to ensure more global representation of participants in microbiome studies.}, }
@article {pmid35152186, year = {2022}, author = {Lim, H and Cankara, F and Tsai, CJ and Keskin, O and Nussinov, R and Gursoy, A}, title = {Artificial intelligence approaches to human-microbiome protein-protein interactions.}, journal = {Current opinion in structural biology}, volume = {73}, number = {}, pages = {102328}, doi = {10.1016/j.sbi.2022.102328}, pmid = {35152186}, issn = {1879-033X}, mesh = {*Artificial Intelligence ; Humans ; *Microbiota ; }, abstract = {Host-microbiome interactions play significant roles in human health and disease. Artificial intelligence approaches have been developed to better understand and predict the molecular interplay between the host and its microbiome. Here, we review recent advancements in computational methods to predict microbial effects on human cells with a special focus on protein-protein interactions. We categorize recent methods from traditional ones to more recent deep learning methods, followed by several challenges and potential solutions in structure-based approaches. This review serves as a brief guide to the current status and future directions in the field.}, }
@article {pmid35151278, year = {2022}, author = {Doocey, CM and Finn, K and Murphy, C and Guinane, CM}, title = {The impact of the human microbiome in tumorigenesis, cancer progression, and biotherapeutic development.}, journal = {BMC microbiology}, volume = {22}, number = {1}, pages = {53}, pmid = {35151278}, issn = {1471-2180}, mesh = {Animals ; Bacteroides fragilis/genetics/pathogenicity ; Carcinogenesis/*genetics/pathology ; Colorectal Neoplasms/*therapy ; Fusobacterium nucleatum/genetics/pathogenicity ; Gastrointestinal Microbiome/genetics/physiology ; Humans ; Mice ; Microbiota/*genetics/physiology ; Probiotics ; Tumor Microenvironment ; Virulence Factors ; }, abstract = {BACKGROUND: Cancer impacts millions of lives globally each year, with approximately 10 million cancer-related deaths recorded worldwide in 2020. Mounting research has recognised the human microbiome as a key area of interest in the pathophysiology of various human diseases including cancer tumorigenesis, progression and in disease outcome. It is suggested that approximately 20% of human cancers may be linked to microbes. Certain residents of the human microbiome have been identified as potentially playing a role, including: Helicobacter pylori, Fusobacterium nucleatum, Escherichia coli, Bacteroides fragilis and Porphyromonas gingivalis.<br><br>MAIN BODY: In this review, we explore the current evidence that indicate a link between the human microbiome and cancer. Microbiome compositional changes have been well documented in cancer patients. Furthermore, pathogenic microbes harbouring specific virulence factors have been implicated in driving the carcinogenic activity of various malignancies including colorectal, gastric and pancreatic cancer. The associated genetic mechanisms with possible roles in cancer will be outlined. It will be indicated which microbes have a potential direct link with cancer cell proliferation, tumorigenesis and disease progression. Recent studies have also linked certain microbial cytotoxins and probiotic strains to cancer cell death, suggesting their potential to target the tumour microenvironment given that cancer cells are integral to its composition. Studies pertaining to such cytotoxic activity have suggested the benefit of microbial therapies in oncological treatment regimes. It is also apparent that bacterial pathogenic protein products encoded for by certain loci may have potential as oncogenic therapeutic targets given their possible role in tumorigenesis.<br><br>CONCLUSION: Research investigating the impact of the human microbiome in cancer has recently gathered pace. Vast amounts of evidence indicate the human microbiome as a potential player in tumorigenesis and progression. Promise in the development of cancer biomarkers and in targeted oncological therapies has also been demonstrated, although more studies are needed. Despite extensive in vitro and in vivo research, clinical studies involving large cohorts of human patients are lacking. The current literature suggests that further intensive research is necessary to validate both the role of the human microbiome in cancer, and the use of microbiome modification in cancer therapy.}, }
@article {pmid35147263, year = {2022}, author = {Wisgrill, L and Fyhrquist, N and Ndika, J and Paalanen, L and Berger, A and Laatikainen, T and Karisola, P and Haahtela, T and Alenius, H}, title = {Bet v 1 triggers antiviral-type immune signalling in birch-pollen-allergic individuals.}, journal = {Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology}, volume = {52}, number = {8}, pages = {929-941}, pmid = {35147263}, issn = {1365-2222}, mesh = {Adolescent ; Allergens ; Antigens, Plant ; Antiviral Agents ; *Betula ; Humans ; *Hypersensitivity ; Immunoglobulin E ; Leukocytes, Mononuclear ; Plant Proteins ; Pollen ; }, abstract = {BACKGROUND: In allergic patients, clinical symptoms caused by pollen remind of symptoms triggered by viral respiratory infections, which are also the main cause of asthmatic exacerbations. In patients sensitized to birch pollen, Bet v 1 is the major symptom-causing allergen. Immune mechanisms driving Bet v 1-related responses of human blood cells have not been fully characterized.<br><br>OBJECTIVE: To characterize the immune response to Bet v 1 in peripheral blood in patients allergic to birch pollen.<br><br>METHODS: The peripheral blood mononuclear cells of birch-allergic (n&#xa0;=&#xa0;24) and non-allergic (n&#xa0;=&#xa0;47) adolescents were stimulated ex-vivo followed by transcriptomic profiling. Systems-biology approaches were employed to decipher disease-relevant gene networks and deconvolution of associated cell populations.<br><br>RESULTS: Solely in birch-allergic patients, co-expression analysis revealed activation of networks of innate immunity and antiviral signalling as the immediate response to Bet v 1&#xa0;stimulation. Toll-like receptors and signal transducer transcription were the main drivers of gene expression patterns. Macrophages and dendritic cells were the main cell subsets responding to Bet v 1.<br><br>In birch-pollen-allergic patients, the activated innate immune networks seem to be, in part, the same as those activated during viral infections. This tendency of the immune system to read pollens as viruses may provide new insight to allergy prevention and treatment.}, }
@article {pmid35145929, year = {2022}, author = {Gao, C and Guo, Y and Chen, F}, title = {Cross-Cohort Microbiome Analysis of Salivary Biomarkers in Patients With Type 2 Diabetes Mellitus.}, journal = {Frontiers in cellular and infection microbiology}, volume = {12}, number = {}, pages = {816526}, pmid = {35145929}, issn = {2235-2988}, mesh = {Biomarkers ; *Diabetes Mellitus, Type 2/microbiology ; Humans ; *Microbiota ; RNA, Ribosomal, 16S/genetics ; Reproducibility of Results ; }, abstract = {Several studies have ascertained differences in salivary microbiota between patients with type 2 diabetes mellitus (T2DM) and healthy populations. However, the predictive accuracy and reproducibility of these 16S rRNA sequencing analyses when applied to other cohorts remain enigmatic. A comprehensive analysis was conducted on the included 470 samples from five researches in publicly available databases. The discrepancy and predictive accuracy of salivary microbiota between T2DM patients and healthy populations were evaluated from multiple perspectives, followed by the identification of salivary biomarkers for DM. Next, a classification model (areas under the curves = 0.92) was developed based on a large sample. The model could be used for clinical diagnosis and prognostic monitoring and as a basis for hypothesis-driven mechanistic researches. Furthermore, the research heterogeneity across geographic regions suggested that microbiological markers might not become a uniform clinical standard in human beings. They rather identify abnormal alterations under the microbiological characteristics of a specific population.}, }
@article {pmid35142027, year = {2022}, author = {Flach, M and Leu, C and Martinisi, A and Skachokova, Z and Frank, S and Tolnay, M and Stahlberg, H and Winkler, DT}, title = {Trans-seeding of Alzheimer-related tau protein by a yeast prion.}, journal = {Alzheimer's &amp; dementia : the journal of the Alzheimer's Association}, volume = {18}, number = {12}, pages = {2481-2492}, pmid = {35142027}, issn = {1552-5279}, mesh = {Mice ; Animals ; Humans ; tau Proteins/metabolism ; *Prions/metabolism ; *Alzheimer Disease/metabolism ; *Tauopathies/pathology ; Saccharomyces cerevisiae/metabolism ; Mice, Transgenic ; }, abstract = {Abnormal tau protein aggregates constitute a hallmark of Alzheimer's disease. The mechanisms underlying the initiation of tau aggregation in sporadic neurodegeneration remain unclear. Here we investigate whether a non-human prion can seed tau aggregation. Due to their structural similarity with tau aggregates, we chose Sup35NM yeast prion domain fibrils for explorative tau seedings. Upon in vitro incubation with tau monomers, Sup35NM fibrils promoted the formation of morphologically distinct tau fibril strains. In vivo, intrahippocampal inoculation of Sup35NM fibrils accentuated tau pathology in P301S tau transgenic mice. Thus, our results provide first in vivo evidence for heterotypic cross-species seeding of a neurodegenerative human prion-like protein by a yeast prion. This opens up the conceptual perspective that non-mammalian prions present in the human microbiome could be involved in the initiation of protein misfolding in neurodegenerative disorders, a mechanism for which we propose the term "trans-seeding."}, }
@article {pmid35140882, year = {2022}, author = {Junca, H and Pieper, DH and Medina, E}, title = {The emerging potential of microbiome transplantation on human health interventions.}, journal = {Computational and structural biotechnology journal}, volume = {20}, number = {}, pages = {615-627}, pmid = {35140882}, issn = {2001-0370}, abstract = {The human microbiome has been the subject of intense research over the past few decades, in particular as a promising area for new clinical interventions. The microbiota colonizing the different body surfaces are of benefit for multiple physiological and metabolic processes of the human host and increasing evidence suggests an association between disturbances in the composition and functionality of the microbiota and several pathological conditions. This has provided a rationale for beneficial modulation of the microbiome. One approach being explored for modulating the microbiota in diseased individuals is transferring microbiota or microbiota constituents from healthy donors via microbiome transplantation. The great success of fecal microbiome transplantation for the treatment of Clostridioides difficile infections has encouraged the application of this procedure for the treatment of other diseases such as vaginal disorders via transplantation of vaginal microbiota, or of skin pathologies via the transplantation of skin microbiota. Microbiome modulation could even become a novel strategy for improving the efficacy of cancer therapies. This review discusses the principle, advantages and limitations of microbiome transplantation as well as different clinical contexts where microbiome transplantation has been applied.}, }
@article {pmid35136968, year = {2022}, author = {Jamrozik, E and Heriot, GS}, title = {Ethics and antibiotic resistance.}, journal = {British medical bulletin}, volume = {141}, number = {1}, pages = {4-14}, pmid = {35136968}, issn = {1471-8391}, support = {/WT_/Wellcome Trust/United Kingdom ; 203132/WT_/Wellcome Trust/United Kingdom ; 221719/WT_/Wellcome Trust/United Kingdom ; 221719/Z/20/Z/WT_/Wellcome Trust/United Kingdom ; }, mesh = {*Anti-Bacterial Agents/therapeutic use ; Drug Resistance, Microbial ; Humans ; *Morals ; }, abstract = {INTRODUCTION OR BACKGROUND: Antibiotic resistance raises ethical issues due to the severe and inequitably distributed consequences caused by individual actions and policies.<br><br>SOURCES OF DATA: Synthesis of ethical, scientific and clinical literature.<br><br>AREAS OF AGREEMENT: Ethical analyses have focused on the moral responsibilities of patients to complete antibiotic courses, resistance as a tragedy of the commons and attempts to limit use through antibiotic stewardship.<br><br>AREAS OF CONTROVERSY: Each of these analyses has significant limitations and can result in self-defeating or overly narrow implications for policy.<br><br>GROWING POINTS: More complex analyses focus on ethical implications of ubiquitous asymptomatic carriage of resistant bacteria, non-linear outcomes within and between patients over time and global variation in resistant disease burdens.<br><br>Neglected topics include the harms of antibiotic use, including off-target effects on the human microbiome, and the lack of evidence guiding most antibiotic prescription decisions.}, }
@article {pmid35132375, year = {2022}, author = {Kozhakhmetov, S and Babenko, D and Kozhakhmetova, S and Tuyakova, A and Nurgaziyev, M and Nurgozhina, A and Muhanbetganov, N and Chulenbayeva, L and Sergazy, S and Gulyayev, A and Aljofan, M and Kushugulova, A}, title = {Therapeutic Potential of Metabolites from Lactobacillus rhamnosus and Mare's Milk in the Treatment of Dysbiosis.}, journal = {BioMed research international}, volume = {2022}, number = {}, pages = {3851478}, pmid = {35132375}, issn = {2314-6141}, mesh = {Animals ; Colitis, Ulcerative/*drug therapy/metabolism/microbiology ; Cytokines/metabolism ; Dextran Sulfate ; Disease Models, Animal ; Dysbiosis/*drug therapy ; Gastrointestinal Microbiome/*drug effects ; Horses ; Lacticaseibacillus rhamnosus/*metabolism ; Mesalamine/pharmacology ; Milk/*metabolism ; Rats ; Rats, Wistar ; }, abstract = {Ulcerative colitis is an inflammatory bowel disease that forms ulcerations in the mucous membrane of the colon and rectum, in which gut microbiota plays a pivotal role in its pathogenesis. Agents modulating microbial dysbiosis caused by colitis can help in the remission of this disease. The current study describes the potential therapeutic effects of active metabolites from Lactobacillus rhamnosus and mare's milk which have potential therapeutic values on the intestinal microbiota and proinflammatory cytokines. The analysis of the V1-V3 16S rDNA site revealed significant changes in the intestinal microbiome composition before and after treatment in the treated group compared to the positive control group that was treated with 5-aminosalicylic acid (5-ASA). So the effect of the study product on dextran sulfate sodium-induced dysbiosis was shown to be more potent than the positive control, 5-ASA. The level of proinflammatory cytokines also decreased under the influence of a biological product.}, }
@article {pmid35125119, year = {2022}, author = {Kuehnast, T and Abbott, C and Pausan, MR and Pearce, DA and Moissl-Eichinger, C and Mahnert, A}, title = {The crewed journey to Mars and its implications for the human microbiome.}, journal = {Microbiome}, volume = {10}, number = {1}, pages = {26}, pmid = {35125119}, issn = {2049-2618}, mesh = {Astronauts ; Confined Spaces ; Humans ; *Mars ; *Microbiota ; *Space Flight ; Spacecraft ; }, abstract = {A human spaceflight to Mars is scheduled for the next decade. In preparation for this unmatched endeavor, a plethora of challenges must be faced prior to the actual journey to Mars. Mission success will depend on the health of its crew and its working capacity. Hence, the journey to Mars will also depend on the microbiome and its far-reaching effects on individual crew health, the spaceship's integrity, and food supply. As human beings rely on their microbiome, these microbes are essential and should be managed to ensure their beneficial effects outweigh potential risks. In this commentary, we focus on the current state of knowledge regarding a healthy (gut) microbiome of space travelers based on research from the International Space Station and simulation experiments on Earth. We further indicate essential knowledge gaps of microbial conditions during long-term space missions in isolated confined space habitats or outposts and give detailed recommendations for microbial monitoring during pre-flight, in-flight, and post-flight. Finally, the conclusion outlines open questions and aspects of space traveler's health beyond the scope of this commentary. Video Abstract.}, }
@article {pmid35122129, year = {2022}, author = {Wang, Y and Wang, Y and Wang, J}, title = {A comprehensive analysis of intratumor microbiome in head and neck squamous cell carcinoma.}, journal = {European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery}, volume = {279}, number = {8}, pages = {4127-4136}, pmid = {35122129}, issn = {1434-4726}, support = {G2020KY0516//Fundamental Research Funds for the Central Universities of Northwestern Polytechnical University/ ; 2021SF-030//Shaanxi Provincial Key Research and Development Program/ ; }, mesh = {Biomarkers, Tumor/genetics ; *Head and Neck Neoplasms ; Humans ; *Microbiota ; Prognosis ; Squamous Cell Carcinoma of Head and Neck ; }, abstract = {PURPOSE: Human microbiome has been considered as the second genome of our body. The intratissue/intratumor microbiome analysis is a relatively new field and deserves more attention. In this study, we conducted a comprehensive analysis of microbiome signatures of head and neck squamous cell carcinoma (HNSC).<br><br>METHODS: The intratumor microbiome profiling and clinicopathological information about a total of 177 HNSC samples, including 155 tumors and 22 adjacent normal tissues, were obtained from The Cancer Microbiome Atlas (TCMA) and The Cancer Genome Atlas (TCGA) databases. We identified the microbes that differed between tumors and normal tissues, and assessed their utility values as diagnostic biomarkers. The microbiome signatures under different conditions of clinicopathological parameters were also analyzed.<br><br>RESULTS: The intratissue microbiome profiles differed between tumor and normal samples of HNSC. The composition of four, six, and six microbes changed in tumors compared to normal tissues at the phylum, order, and genus levels, respectively (P&#x2009;<&#x2009;0.05). Eight of the differential microbes performed well in distinguishing tumors from normal tissues (AUC&#x2009;>&#x2009;0.7, P&#x2009;&#x2264;&#x2009;0.001). The microbiome signature was found to be associated with tumor&#xa0;clinicopathological&#xa0;characteristics such as host-gender, host-age, tumor stage, and neoplasm histologic grade.<br><br>CONCLUSION: Overall, our results revealed an intratissue microbiome signature of HNSC. We concluded that the intratumor microbiome signature may also reflect human biology in both healthy and disease status, and provide novel perspective for microbiota research about their roles in tumors.}, }
@article {pmid35118003, year = {2021}, author = {Abou Chacra, L and Fenollar, F and Diop, K}, title = {Bacterial Vaginosis: What Do We Currently Know?.}, journal = {Frontiers in cellular and infection microbiology}, volume = {11}, number = {}, pages = {672429}, pmid = {35118003}, issn = {2235-2988}, mesh = {Ecosystem ; Female ; Gardnerella vaginalis ; Humans ; Lactobacillus ; Vagina/microbiology ; *Vaginosis, Bacterial/microbiology ; }, abstract = {The vaginal microbiome is a well-defined compartment of the human microbiome. It has unique conditions, characterized by the dominance of one bacterial species, the Lactobacilli. This microbiota manifests itself by a low degree of diversity and by a strong dynamic of change in its composition under the influence of various exogenous and endogenous factors. The increase in diversity may paradoxically be associated with dysbiosis, such as bacterial vaginosis (BV). BV is the result of a disturbance in the vaginal ecosystem; i.e., a sudden replacement of Lactobacilli by anaerobic bacteria such as Gardnerella vaginalis, Atopobium vaginae, Ureaplasma urealyticum, Mycoplasma hominis, and others. It is the most common cause of vaginal discharge in women of childbearing age, approximately 30% of all causes. The etiology of this dysbiosis remains unknown, but its health consequences are significant, including obstetrical complications, increased risk of sexually transmitted infections and urogenital infections. Its diagnosis is based on Amsel's clinical criteria and/or a gram stain based on the Nugent score. While both of these methods have been widely applied worldwide for approximately three decades, Nugent score are still considered the "gold standard" of BV diagnostic tools. Given the limitations of these tools, methods based on molecular biology have been developed as alternative rational strategies for the diagnosis of BV. The treatment of BV aims at restoring the balance of the vaginal flora to stop the proliferation of harmful microorganisms. Prescription of antibiotics such as metronidazole, clindamycin, etc. is recommended. Faced with the considerable uncertainty about the cause of BV, the high rate of recurrence, the unacceptable treatment options, and clinical management which is often insensitive and inconsistent, research on this topic is intensifying. Knowledge of its composition and its associated variations represents the key element in improving the therapeutic management of patients with the most suitable treatments possible.}, }
@article {pmid35111779, year = {2021}, author = {Wehedy, E and Shatat, IF and Al Khodor, S}, title = {The Human Microbiome in Chronic Kidney Disease: A Double-Edged Sword.}, journal = {Frontiers in medicine}, volume = {8}, number = {}, pages = {790783}, pmid = {35111779}, issn = {2296-858X}, abstract = {Chronic kidney disease (CKD) is an increasing global health burden. Current treatments for CKD include therapeutics to target factors that contribute to CKD progression, including renin-angiotensin-aldosterone system inhibitors, and drugs to control blood pressure and proteinuria control. Recently, associations between chronic disease processes and the human microbiota and its metabolites have been demonstrated. Dysbiosis-a change in the microbial diversity-has been observed in patients with CKD. The relationship between CKD and dysbiosis is bidirectional; gut-derived metabolites and toxins affect the progression of CKD, and the uremic milieu affects the microbiota. The accumulation of microbial metabolites and toxins is linked to the loss of kidney functions and increased mortality risk, yet renoprotective metabolites such as short-chain fatty acids and bile acids help restore kidney functions and increase the survival rate in CKD patients. Specific dietary interventions to alter the gut microbiome could improve clinical outcomes in patients with CKD. Low-protein and high-fiber diets increase the abundance of bacteria that produce short-chain fatty acids and anti-inflammatory bacteria. Fluctuations in the urinary microbiome are linked to increased susceptibility to infection and antibiotic resistance. In this review, we describe the potential role of the gut, urinary and blood microbiome in CKD pathophysiology and assess the feasibility of modulating the gut microbiota as a therapeutic tool for treating CKD.}, }
@article {pmid35107701, year = {2022}, author = {Vandamme, P and Peeters, C and Seth-Smith, HMB and Schmid, H and Cnockaert, M and Egli, A and Goldenberger, D}, title = {Description of Pseudoclavibacter triregionum sp. nov. from human blood and Pseudoclavibacter albus comb. nov., and revised classification of the genus Pseudoclavibacter: proposal of Caespitibacter gen. nov., with Caespitibacter soli comb. nov. and Caespitibacter caeni comb. nov.}, journal = {Antonie van Leeuwenhoek}, volume = {115}, number = {4}, pages = {461-472}, pmid = {35107701}, issn = {1572-9699}, mesh = {Bacterial Typing Techniques ; DNA, Bacterial/chemistry/genetics ; *Fatty Acids/analysis ; Humans ; Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; }, abstract = {We present polyphasic taxonomic data to demonstrate that strain 125703-2019[T], a human blood isolate, represents a novel species within the genus Pseudoclavibacter, and to reclassify the illegitimate Zimmermannella alba Lin et al., 2004 as Pseudoclavibacter albus comb. nov. Upon primary isolation, strain 125703-2019[T] could not be identified reliably using MALDI-TOF mass spectrometry during routine diagnostic work, but partial 16S rRNA gene sequence analysis revealed that it belonged to the genus Pseudoclavibacter. Average nucleotide identity and digital DNA-DNA hybridisation analyses confirmed that it represented a novel species within this genus. A detailed physiological characterisation yielded differential tests between the novel species and its nearest neighbor taxa, which could also be differentiated using MALDI-TOF mass spectrometry. We propose to formally classify this strain into the novel species Pseudoclavibacter triregionum sp. nov., with strain 125703-2019[T] (= R-76471[T], LMG 31777[T], CCUG 74796[T]) as the type strain. The whole-genome assembly of strain 125703-2019[T] has a size of 2.4 Mb and a G + C content of 72.74%. A Pseudoclavibacter pangenome analysis revealed that 667 gene clusters were exclusively present in strain 125703-2019[T]. While these gene clusters were enriched in several COG functional categories, this analysis did not reveal functions that explained the occurrence of this species in human infection. Finally, several phylogenetic and phylogenomic analyses demonstrated that the genus Pseudoclavibacter is polyphyletic with Pseudoclavibacter soli and Pseudoclavibacter caeni representing a unique and deeply branching line of descent within the family Microbacteriaceae. We therefore also propose to reclassify both species into the novel genus Caespitibacter gen. nov. as Caespitibacter soli comb. nov. and Caespitibacter caeni comb. nov., respectively, and with C. soli comb. nov. as the type species.}, }
@article {pmid35105664, year = {2022}, author = {de Vos, WM and Tilg, H and Van Hul, M and Cani, PD}, title = {Gut microbiome and health: mechanistic insights.}, journal = {Gut}, volume = {71}, number = {5}, pages = {1020-1032}, pmid = {35105664}, issn = {1468-3288}, mesh = {Bacteria/metabolism ; Bile Acids and Salts/metabolism ; *Diabetes Mellitus, Type 2 ; Fatty Acids, Volatile/metabolism ; *Gastrointestinal Microbiome ; Humans ; Receptors, G-Protein-Coupled/metabolism ; }, abstract = {The gut microbiota is now considered as one of the key elements contributing to the regulation of host health. Virtually all our body sites are colonised by microbes suggesting different types of crosstalk with our organs. Because of the development of molecular tools and techniques (ie, metagenomic, metabolomic, lipidomic, metatranscriptomic), the complex interactions occurring between the host and the different microorganisms are progressively being deciphered. Nowadays, gut microbiota deviations are linked with many diseases including obesity, type 2 diabetes, hepatic steatosis, intestinal bowel diseases (IBDs) and several types of cancer. Thus, suggesting that various pathways involved in immunity, energy, lipid and glucose metabolism are affected.In this review, specific attention is given to provide a critical evaluation of the current understanding in this field. Numerous molecular mechanisms explaining how gut bacteria might be causally linked with the protection or the onset of diseases are discussed. We examine well-established metabolites (ie, short-chain fatty acids, bile acids, trimethylamine N-oxide) and extend this to more recently identified molecular actors (ie, endocannabinoids, bioactive lipids, phenolic-derived compounds, advanced glycation end products and enterosynes) and their specific receptors such as peroxisome proliferator-activated receptor alpha (PPARα) and gamma (PPARγ), aryl hydrocarbon receptor (AhR), and G protein-coupled receptors (ie, GPR41, GPR43, GPR119, Takeda G protein-coupled receptor 5).Altogether, understanding the complexity and the molecular aspects linking gut microbes to health will help to set the basis for novel therapies that are already being developed.}, }
@article {pmid35103486, year = {2022}, author = {Shenhav, L and Azad, MB}, title = {Using Community Ecology Theory and Computational Microbiome Methods To Study Human Milk as a Biological System.}, journal = {mSystems}, volume = {7}, number = {1}, pages = {e0113221}, pmid = {35103486}, issn = {2379-5077}, mesh = {Infant ; Female ; Humans ; *Milk, Human ; Cross-Sectional Studies ; Lactation ; *Microbiota ; Breast Feeding ; }, abstract = {Human milk is a complex and dynamic biological system that has evolved to optimally nourish and protect human infants. Yet, according to a recent priority-setting review, "our current understanding of human milk composition and its individual components and their functions fails to fully recognize the importance of the chronobiology and systems biology of human milk in the context of milk synthesis, optimal timing and duration of feeding, and period of lactation" (P. Christian et al., Am J Clin Nutr 113:1063-1072, 2021, https://doi.org/10.1093/ajcn/nqab075). We attribute this critical knowledge gap to three major reasons as follows. (i) Studies have typically examined each subsystem of the mother-milk-infant "triad" in isolation and often focus on a single element or component (e.g., maternal lactation physiology or milk microbiome or milk oligosaccharides or infant microbiome or infant gut physiology). This undermines our ability to develop comprehensive representations of the interactions between these elements and study their response to external perturbations. (ii) Multiomics studies are often cross-sectional, presenting a snapshot of milk composition, largely ignoring the temporal variability during lactation. The lack of temporal resolution precludes the characterization and inference of robust interactions between the dynamic subsystems of the triad. (iii) We lack computational methods to represent and decipher the complex ecosystem of the mother-milk-infant triad and its environment. In this review, we advocate for longitudinal multiomics data collection and demonstrate how incorporating knowledge gleaned from microbial community ecology and computational methods developed for microbiome research can serve as an anchor to advance the study of human milk and its many components as a "system within a system."}, }
@article {pmid35101562, year = {2022}, author = {Das, S and Goswami, AM and Saha, T}, title = {An insight into the role of protein kinases as virulent factors, regulating pathogenic attributes in Candida albicans.}, journal = {Microbial pathogenesis}, volume = {164}, number = {}, pages = {105418}, doi = {10.1016/j.micpath.2022.105418}, pmid = {35101562}, issn = {1096-1208}, mesh = {*Candida albicans ; *Candidiasis/pathology ; Fungal Proteins/metabolism ; Humans ; Protein Kinases ; Virulence ; Virulence Factors/metabolism ; }, abstract = {Candida albicans is a polymorphic, opportunistic pathogen, member of normal human microbiome causing candidiasis. It causes wide range of infections from superficial skin infections to life-threatening systemic infections. The pathogenicity in C. albicans attributes through several morphological characteristics and virulence factors. These morphological features are regulated by various molecules among which kinases are the most important. Several kinases and kinase signaling cascades play a well established role in Candidiasis. In this review we present an update on our current understanding of the pathogenicity attributes which is regulated by kinases as virulence factors.}, }
@article {pmid35101266, year = {2022}, author = {Kantele, A and Rombo, L and Vene, S and Kundi, M and Lindquist, L and Erra, EO}, title = {Three-dose versus four-dose primary schedules for tick-borne encephalitis (TBE) vaccine FSME-immun for those aged 50 years or older: A single-centre, open-label, randomized controlled trial.}, journal = {Vaccine}, volume = {40}, number = {9}, pages = {1299-1305}, doi = {10.1016/j.vaccine.2022.01.022}, pmid = {35101266}, issn = {1873-2518}, mesh = {Adult ; Antibodies, Viral ; *Encephalitis Viruses, Tick-Borne ; *Encephalitis, Tick-Borne/prevention &amp; control ; Humans ; Immunization Schedule ; Middle Aged ; *Viral Vaccines ; }, abstract = {BACKGROUND: TBE vaccination failures among those past middle age have raised concern about immune response declining with age. We investigated immunogenicity of the TBE-vaccine FSME-Immun among those aged 50+ years using the standard three-dose primary series and alternative four-dose schedules.<br><br>METHODS: In this single-centre, open-label, randomized controlled trial, 200 TBE-naive Swedish adults were given primary TBE vaccination with FSME-Immun. Those aged 50+ years (n&#xa0;=&#xa0;150) were randomized to receive the standard three-dose (days 0-30-360) or one of two four-dose series (0-7-21-360; 0-30-90-360). For participants&#xa0;<&#xa0;50&#xa0;years (n&#xa0;=&#xa0;50) the standard three-dose schedule was used. Titres of neutralizing antibodies were determined on days 0, 60, 120, 360, and 400. The main outcome was the log titre of TBE virus-specific neutralizing antibodies on day 400.<br><br>RESULTS: The three-dose schedule yielded lower antibody titres among those aged 50+ years than the younger participants on day 400 (geometric mean titre 41 versus 74, p&#xa0;<&#xa0;0.05). The older group showed higher titres for the four-dose 0-7-21-360 than the standard three-dose schedule both on day 400 (103 versus 41, p&#xa0;<&#xa0;0.01; primary end point) and at the other testing points (days 60, 120, 360). Using the other four-dose schedule (0-30-90-360), no such difference was observed on day 400 (63 versus 41, NS).<br><br>CONCLUSION: Immune response to the TBE vaccine declined with age. A four-dose schedule (0-7-21-360) may benefit those aged 50&#xa0;years or older. This study is registered at ClinicalTrials.gov, NCT01361776.}, }
@article {pmid35096962, year = {2021}, author = {Zhang, Y and Zhou, L and Xia, J and Dong, C and Luo, X}, title = {Human Microbiome and Its Medical Applications.}, journal = {Frontiers in molecular biosciences}, volume = {8}, number = {}, pages = {703585}, pmid = {35096962}, issn = {2296-889X}, abstract = {The commensal microbiome is essential for human health and is involved in many processes in the human body, such as the metabolism process and immune system activation. Emerging evidence implies that specific changes in the microbiome participate in the development of various diseases, including diabetes, liver diseases, tumors, and pathogen infections. Thus, intervention on the microbiome is becoming a novel and effective method to treat such diseases. Synthetic biology empowers researchers to create strains with unique and complex functions, making the use of engineered microbes for clinical applications attainable. The aim of this review is to summarize recent advances about the roles of the microbiome in certain diseases and the underlying mechanisms, as well as the use of engineered microbes in the prevention, detection, and treatment of various diseases.}, }
@article {pmid35094706, year = {2022}, author = {Alamri, A and AlKhater, SA}, title = {Evaluating the knowledge on microbiome and dysbiosis in allergic diseases among medical sciences students in Saudi Arabia.}, journal = {Clinical and molecular allergy : CMA}, volume = {20}, number = {1}, pages = {2}, pmid = {35094706}, issn = {1476-7961}, abstract = {BACKGROUND: Microbiome science deals with the development of diseases that are derived from the interaction between the host immune system and microbes. Microbiome disturbance or dysbiosis has been increasingly recognized as an important contributor to the pathogenesis of allergic diseases. Thus, this field is pivotal in the management of allergic disorders. Despite the increasing prevalence of allergic disorders in Saudi Arabia, medical students lack knowledge of microbiome science. Therefore, this study aimed to assess the level of knowledge of medical sciences students on the human microbiome, dysbiosis, and management of the impaired microbiome with a focus on allergic diseases and asthma.<br><br>METHODS: An online survey was designed, validated, and distributed to 100 final-year students and interns majoring in clinical nutrition, public health, and clinical laboratory sciences at a single university in Saudi Arabia. The study period was from November 2020 to January 2021.<br><br>RESULTS: The overall knowledge of the human microbiome was adequate among the participants, but their understanding of dysbiosis and management of the impaired microbiome was low to moderate. Knowledge of dysbiosis management was significantly higher in students majoring in clinical nutrition than in those majoring in public health and clinical laboratory sciences.<br><br>CONCLUSIONS: Collectively, this study provides the first evidence that knowledge of specific domains of microbiome science among a cohort of medical sciences students in Saudi Arabia is insufficient. Large-scale studies are warranted to confirm these observations at a national level, and specific curriculum modifications are necessary to improve the knowledge of future healthcare professionals about clinical applications of microbiome science.}, }
@article {pmid35093602, year = {2022}, author = {Zhang, X and Zhai, Q and Wang, J and Ma, X and Xing, B and Fan, H and Gao, Z and Zhao, F and Liu, W}, title = {Variation of the Vaginal Microbiome During and After Pregnancy in Chinese Women.}, journal = {Genomics, proteomics &amp; bioinformatics}, volume = {20}, number = {2}, pages = {322-333}, pmid = {35093602}, issn = {2210-3244}, mesh = {Humans ; Infant, Newborn ; Pregnancy ; Female ; *Premature Birth/microbiology ; Vagina/microbiology ; *Microbiota/genetics ; RNA, Ribosomal, 16S/genetics ; Lactobacillus/genetics ; Bacteria/genetics ; China/epidemiology ; }, abstract = {A comprehensive profiling of the vaginal microbial communities and their variability enables an accurate description of the microbiome in women. However, there is a lack of studies available on Chinese women. In the present study, the composition of the vaginal microbiota during pregnancy and the 6-week postpartum period of 454 Chinese women was characterized by sequencing the V3-V4 region of the 16S ribosomal RNA (rRNA) gene. The vaginal microbiome showed variations during pregnancy and the postpartum period based on the abortion history, hypertensive disorders, delivery mode, and maternal age. Co-variation of 22 bacterial taxa, including the Lactobacillus genus and two of its species, may account for the common characteristics of the vaginal microbiome under scenarios of different medical histories and pregnancy outcomes. In contrast, discriminant bacterial species were significantly different between women who had preterm birth (PTB) with and without premature rupture of membranes (PROM), and the community state type (CST) IV-A without any predominant Lactobacillus species in the microbiota was more prevalent during pregnancy in the PROM-PTB cases, suggesting that specific bacterial species could be considered to distinguish between different types of PTB. By providing data on Chinese women, this study will enrich the knowledge of the human microbiome and contribute to a better understanding of the association between the vaginal microbiome and reproductive health.}, }
@article {pmid35092364, year = {2022}, author = {McClure, S and Enam, F and Arnold, J and Mimee, M}, title = {Proceedings from the 3rd International Conference on Microbiome Engineering.}, journal = {Biotechnology progress}, volume = {38}, number = {3}, pages = {e3241}, pmid = {35092364}, issn = {1520-6033}, mesh = {*Bacteriophages/genetics ; Bone and Bones/chemistry ; Humans ; *Microbiota/genetics ; Prebiotics/analysis ; *Probiotics/therapeutic use ; }, abstract = {The human microbiome has been inextricably linked to multiple facets of human physiology. From an engineering standpoint, the ability to precisely control the composition and activity of the microbiome holds great promise for furthering our understanding of disease etiology and for new avenues of therapeutic and diagnostic agents. While the field of microbiome research is still in its infancy, growing engineering efforts are emerging to enable new studies in the microbiome and to rapidly translate these findings to microbiome-based interventions. At the 3rd International Conference on Microbiome Engineering, leading experts in the field presented state-of-the-art work in microbiome engineering, discussing probiotics, prebiotics, engineered microbes, microbially derived biomolecules, and bacteriophage.}, }
@article {pmid35091681, year = {2022}, author = {Saliba, J and Coutaud, B and Makhani, K and Epstein Roth, N and Jackson, J and Park, JY and Gagnon, N and Costa, P and Jeyakumar, T and Bury, M and Beauchemin, N and Mann, KK and Blank, V}, title = {Loss of NFE2L3 protects against inflammation-induced colorectal cancer through modulation of the tumor microenvironment.}, journal = {Oncogene}, volume = {41}, number = {11}, pages = {1563-1575}, pmid = {35091681}, issn = {1476-5594}, support = {MOP-97932//CIHR/Canada ; PJT-152937//CIHR/Canada ; }, mesh = {Animals ; Basic-Leucine Zipper Transcription Factors/metabolism ; *Colorectal Neoplasms/genetics ; Forkhead Transcription Factors ; Humans ; Inflammation/genetics ; Interleukin-33 ; Mice ; T-Lymphocytes, Regulatory ; *Tumor Microenvironment/genetics ; }, abstract = {We investigated the role of the NFE2L3 transcription factor in inflammation-induced colorectal cancer. Our studies revealed that Nfe2l3[-/-] mice exhibit significantly less inflammation in the colon, reduced tumor size and numbers, and skewed localization of tumors with a more pronounced decrease of tumors in the distal colon. CIBERSORT analysis of RNA-seq data from normal and tumor tissue predicted a reduction in mast cells in Nfe2l3[-/-] animals, which was confirmed by toluidine blue staining. Concomitantly, the transcript levels of Il33 and Rab27a, both important regulators of mast cells, were reduced and increased, respectively, in the colorectal tumors of Nfe2l3[-/-] mice. Furthermore, we validated NFE2L3 binding to the regulatory sequences of the IL33 and RAB27A loci in human colorectal carcinoma cells. Using digital spatial profiling, we found that Nfe2l3[-/-] mice presented elevated FOXP3 and immune checkpoint markers CTLA4, TIM3, and LAG3, suggesting an increase in Treg counts. Staining for CD3 and FOXP3 confirmed a significant increase in immunosuppressive Tregs in the colon of Nfe2l3[-/-] animals. Also, Human Microbiome Project (HMP2) data showed that NFE2L3 transcript levels are higher in the rectum of ulcerative colitis patients. The observed changes in the tumor microenvironment provide new insights into the molecular differences regarding colon cancer sidedness. This may be exploited for the treatment of early-onset colorectal cancer as this emerging subtype primarily displays distal/left-sided tumors.}, }
@article {pmid35086550, year = {2022}, author = {Romito, I and Porru, M and Braghini, MR and Pompili, L and Panera, N and Crudele, A and Gnani, D and De Stefanis, C and Scarsella, M and Pomella, S and Mortera, SL and de Billy, E and Conti, AL and Marzano, V and Putignani, L and Vinciguerra, M and Balsano, C and Pastore, A and Rota, R and Tartaglia, M and Leonetti, C and Alisi, A}, title = {Correction to: Focal adhesion kinase inhibitor TAE226 combined with Sorafenib slows down hepatocellular carcinoma by multiple epigenetic effects.}, journal = {Journal of experimental &amp; clinical cancer research : CR}, volume = {41}, number = {1}, pages = {40}, pmid = {35086550}, issn = {1756-9966}, }
@article {pmid35078284, year = {2022}, author = {Su, Z and Jia, X and Fan, Y and Zhao, F and Qiao, Y}, title = {[Progress of Research on the Relationship between Lung Microbiome and Lung Cancer].}, journal = {Zhongguo fei ai za zhi = Chinese journal of lung cancer}, volume = {25}, number = {1}, pages = {40-45}, pmid = {35078284}, issn = {1999-6187}, mesh = {Humans ; Lung ; Lung Diseases ; *Lung Neoplasms ; *Microbiota ; Oncogenes ; }, abstract = {The microbiota plays an important role in the biological functions of the human body and is associated with various disease states such as inflammation (gastritis, hepatitis) and cancer (stomach, cervical, liver). The Human Microbiome Project painted a panorama of human microorganisms in its first phase, incorporating body parts such as the nasal cavity, oral cavity, intestine, vagina and skin, while the lungs were considered a sterile environment. However, studies in recent years have confirmed the presence of a rich microbial community in the lung, and the association of this lung microbiota with lung disease has become a hot topic of research. Current research has found that patients with lung cancer have a specific microbiota compared to healthy individuals or patients with lung disease. Even in patients with lung cancer, a lung microbiota specific to the tumor site is present. In addition, different pathological types and metastatic status of lung cancer can lead to differences in microbiota. Mechanistic studies have found that the lung microbiota may influence lung cancer development by affecting the immune response. Clinical studies on lung microbiota and immunotherapy are still in the preliminary stage. More relevant studies are needed in the future to provide high-quality evidence to further understand the oncogenic mechanisms of lung microbiota and provide new ideas for clinical treatment. This paper briefly reviews the progress of lung microbiota research in terms of its relevance to lung cancer, possible molecular mechanisms and applications in clinical treatment, and provides an outlook for future research. .}, }
@article {pmid35070166, year = {2022}, author = {Hou, Q and Pucci, F and Pan, F and Xue, F and Rooman, M and Feng, Q}, title = {Using metagenomic data to boost protein structure prediction and discovery.}, journal = {Computational and structural biotechnology journal}, volume = {20}, number = {}, pages = {434-442}, pmid = {35070166}, issn = {2001-0370}, abstract = {Over the past decade, metagenomic sequencing approaches have been providing an ever-increasing amount of protein sequence data at an astonishing rate. These constitute an invaluable source of information which has been exploited in various research fields such as the study of the role of the gut microbiota in human diseases and aging. However, only a small fraction of all metagenomic sequences collected have been functionally or structurally characterized, leaving much of them completely unexplored. Here, we review how this information has been used in protein structure prediction and protein discovery. We begin by presenting some widely used metagenomic databases and analyze in detail how metagenomic data has contributed to the impressive improvement in the accuracy of structure prediction methods in recent years. We then examine how metagenomic information can be exploited to annotate protein sequences. More specifically, we focus on the role of metagenomes in the discovery of enzymes and new CRISPR-Cas systems, and in the identification of antibiotic resistance genes. With this review, we provide an overview of how metagenomic data is currently revolutionizing our understanding of protein science.}, }
@article {pmid35065652, year = {2022}, author = {Salachan, PV and Sørensen, KD}, title = {Dysbiotic microbes and how to find them: a review of microbiome profiling in prostate cancer.}, journal = {Journal of experimental &amp; clinical cancer research : CR}, volume = {41}, number = {1}, pages = {31}, pmid = {35065652}, issn = {1756-9966}, mesh = {Dysbiosis/*physiopathology ; Humans ; Male ; Microbiota/*physiology ; Prostatic Neoplasms/*physiopathology ; }, abstract = {The role of the microbiota in human health and disease is well established, including its effects on several cancer types. However, the role of microbial dysbiosis in prostate cancer development, progression, and response to treatment is less well understood. This knowledge gap could perhaps be implicated in the lack of better risk stratification and prognostic tools that incorporate risk factors such as bacterial infections and inflammatory signatures. With over a decade's research investigating associations between microbiome and prostate carcinogenesis, we are ever closer to finding the crucial biological link between the two. Yet, definitive answers remain elusive, calling for continued research into this field. In this review, we outline the three frequently used NGS based analysis methodologies that are used for microbiome profiling, thereby serving as a quick guide for future microbiome research. We next provide a detailed overview of the current knowledge of the role of the human microbiome in prostate cancer development, progression, and treatment response. Finally, we describe proposed mechanisms of host-microbe interactions that could lead to prostate cancer development, progression or treatment response.}, }
@article {pmid35061732, year = {2022}, author = {Hyde, ER and Lozano, H and Cox, S}, title = {BIOME-Preserve: A novel storage and transport medium for preserving anaerobic microbiota samples for culture recovery.}, journal = {PloS one}, volume = {17}, number = {1}, pages = {e0261820}, pmid = {35061732}, issn = {1932-6203}, mesh = {Anaerobiosis ; *Bacteria/classification/genetics ; Feces/*microbiology ; Female ; Humans ; Male ; *Microbiota ; *Preservation, Biological ; *Specimen Handling ; }, abstract = {Sequencing-based protocols for studying the human microbiome have unearthed a wealth of information about the relationship between the microbiome and human health. But these microbes cannot be leveraged as therapeutic targets without culture-based studies to phenotype species of interest and to establish culture collections for use in animal models. Traditional sample collection protocols are focused on preserving nucleic acids and metabolites and are largely inappropriate for preserving sensitive anaerobic bacteria for later culture recovery. Here we introduce a novel microbiome preservation kit (BIOME-Preserve) that facilitates recovery of anaerobic bacteria from human stool. Using a combination of culture recovery and shallow whole-genome shotgun sequencing, we characterized the anaerobes cultured from fresh human stool and from human stool held at room temperature in BIOME-Preserve for up to 120 hours. We recovered several species of interest to microbiome researchers, including Bifidobacterium spp., Bacteroides spp., Blautia spp., Eubacterium halii (now Anaerobutyricum hallii), Akkermansia muciniphila, and Faecalibacterium prausnitzii. We also demonstrated that freezing at -80°C did not adversely affect our ability to culture organisms from BIOME-Preserve, suggesting that it is appropriate both as a transport medium and as a medium for longer-term ultra-cold storage. Together, our results suggest BIOME-Preserve is practical for the collection, transport, and culture of anaerobic bacteria from human samples and can help enable researchers to better understand the link between the microbiome and human health and how to leverage that link through novel microbiome-based therapeutics.}, }
@article {pmid35056496, year = {2021}, author = {Qiao, W and Liu, F and Wan, X and Qiao, Y and Li, R and Wu, Z and Saris, PEJ and Xu, H and Qiao, M}, title = {Genomic Features and Construction of Streamlined Genome Chassis of Nisin Z Producer Lactococcus lactis N8.}, journal = {Microorganisms}, volume = {10}, number = {1}, pages = {}, pmid = {35056496}, issn = {2076-2607}, support = {31770102//National Natural Science Foundation of China/ ; 200050//Jane and Aatos Erkko Foundation/ ; }, abstract = {Lactococcus lactis is a commonly used fermenting bacteria in cheese, beverages and meat products. Due to the lack of simplified chassis strains, it has not been widely used in the fields of synthetic biology. Thus, the construction of lactic acid bacteria chassis strains becomes more and more important. In this study, we performed whole genome sequencing, annotation and analysis of L. lactis N8. Based on the genome analysis, we found that L. lactis N8 contains two large plasmids, and the function prediction of the plasmids shows that some regions are related to carbohydrate transport/metabolism, multi-stress resistance and amino acid uptake. L. lactis N8 contains a total of seven prophage-related fragments and twelve genomic islands. A gene cluster encoding a hybrid NRPS-PKS system that was found in L. lactis N8 reveals that the strain has the potential to synthesize novel secondary metabolites. Furthermore, we have constructed a simplified genome chassis of L. lactis N8 and achieved the largest amount of deletion of L. lactis so far. Taken together, the present study offers further insights into the function and potential role of L. lactis N8 as a model strain of lactic acid bacteria and lays the foundation for its application in the field of synthetic biology.}, }
@article {pmid35054168, year = {2021}, author = {Gouello, A and Dunyach-Remy, C and Siatka, C and Lavigne, JP}, title = {Analysis of Microbial Communities: An Emerging Tool in Forensic Sciences.}, journal = {Diagnostics (Basel, Switzerland)}, volume = {12}, number = {1}, pages = {}, pmid = {35054168}, issn = {2075-4418}, abstract = {The objective of forensic sciences is to find clues in a crime scene in order to reconstruct the scenario. Classical samples include DNA or fingerprints, but both have inherent limitations and can be uninformative. Another type of sample has emerged recently in the form of the microbiome. Supported by the Human Microbiome Project, the characteristics of the microbial communities provide real potential in forensics. They are highly specific and can be used to differentiate and classify the originating body site of a human biological trace. Skin microbiota is also highly specific and different between individuals, leading to its possibility as an identification tool. By extension, the possibilities of the microbial communities to be deposited on everyday objects has also been explored. Other uses include the determination of the post-mortem interval or the analysis of soil communities. One challenge is that the microbiome changes over time and can be influenced by many environmental and lifestyle factors. This review offers an overview of the main methods and applications to demonstrate the benefit of the microbiome to provide forensically relevant information.}, }
@article {pmid35053587, year = {2022}, author = {Kato, I and Zhang, J and Sun, J}, title = {Bacterial-Viral Interactions in Human Orodigestive and Female Genital Tract Cancers: A Summary of Epidemiologic and Laboratory Evidence.}, journal = {Cancers}, volume = {14}, number = {2}, pages = {}, pmid = {35053587}, issn = {2072-6694}, support = {R01 DK105118, R01DK114126/NH/NIH HHS/United States ; CDMRP BC191198//Department of Defence/ ; I01BX004824-01//Veterans for America/ ; }, abstract = {Infectious agents, including viruses, bacteria, fungi, and parasites, have been linked to pathogenesis of human cancers, whereas viruses and bacteria account for more than 99% of infection associated cancers. The human microbiome consists of not only bacteria, but also viruses and fungi. The microbiome co-residing in specific anatomic niches may modulate oncologic potentials of infectious agents in carcinogenesis. In this review, we focused on interactions between viruses and bacteria for cancers arising from the orodigestive tract and the female genital tract. We examined the interactions of these two different biological entities in the context of human carcinogenesis in the following three fashions: (1) direct interactions, (2) indirect interactions, and (3) no interaction between the two groups, but both acting on the same host carcinogenic pathways, yielding synergistic or additive effects in human cancers, e.g., head and neck cancer, liver cancer, colon cancer, gastric cancer, and cervical cancer. We discuss the progress in the current literature and summarize the mechanisms of host-viral-bacterial interactions in various human cancers. Our goal was to evaluate existing evidence and identify gaps in the knowledge for future directions in infection and cancer.}, }
@article {pmid35052575, year = {2021}, author = {Forero-Rodríguez, LJ and Josephs-Spaulding, J and Flor, S and Pinzón, A and Kaleta, C}, title = {Parkinson's Disease and the Metal-Microbiome-Gut-Brain Axis: A Systems Toxicology Approach.}, journal = {Antioxidants (Basel, Switzerland)}, volume = {11}, number = {1}, pages = {}, pmid = {35052575}, issn = {2076-3921}, support = {EXC 2167//Precision Medicine in Chronic Inflammation/ ; FOR5042//Research Unit miTarget/ ; }, abstract = {Parkinson's Disease (PD) is a neurodegenerative disease, leading to motor and non-motor complications. Autonomic alterations, including gastrointestinal symptoms, precede motor defects and act as early warning signs. Chronic exposure to dietary, environmental heavy metals impacts the gastrointestinal system and host-associated microbiome, eventually affecting the central nervous system. The correlation between dysbiosis and PD suggests a functional and bidirectional communication between the gut and the brain. The bioaccumulation of metals promotes stress mechanisms by increasing reactive oxygen species, likely altering the bidirectional gut-brain link. To better understand the differing molecular mechanisms underlying PD, integrative modeling approaches are necessary to connect multifactorial perturbations in this heterogeneous disorder. By exploring the effects of gut microbiota modulation on dietary heavy metal exposure in relation to PD onset, the modification of the host-associated microbiome to mitigate neurological stress may be a future treatment option against neurodegeneration through bioremediation. The progressive movement towards a systems toxicology framework for precision medicine can uncover molecular mechanisms underlying PD onset such as metal regulation and microbial community interactions by developing predictive models to better understand PD etiology to identify options for novel treatments and beyond. Several methodologies recently addressed the complexity of this interaction from different perspectives; however, to date, a comprehensive review of these approaches is still lacking. Therefore, our main aim through this manuscript is to fill this gap in the scientific literature by reviewing recently published papers to address the surrounding questions regarding the underlying molecular mechanisms between metals, microbiota, and the gut-brain-axis, as well as the regulation of this system to prevent neurodegeneration.}, }
@article {pmid35047812, year = {2022}, author = {Banerjee, K and Chen, J and Zhan, X}, title = {Adaptive and powerful microbiome multivariate association analysis via feature selection.}, journal = {NAR genomics and bioinformatics}, volume = {4}, number = {1}, pages = {lqab120}, pmid = {35047812}, issn = {2631-9268}, abstract = {The important role of human microbiome is being increasingly recognized in health and disease conditions. Since microbiome data is typically high dimensional, one popular mode of statistical association analysis for microbiome data is to pool individual microbial features into a group, and then conduct group-based multivariate association analysis. A corresponding challenge within this approach is to achieve adequate power to detect an association signal between a group of microbial features and the outcome of interest across a wide range of scenarios. Recognizing some existing methods' susceptibility to the adverse effects of noise accumulation, we introduce the Adaptive Microbiome Association Test (AMAT), a novel and powerful tool for multivariate microbiome association analysis, which unifies both blessings of feature selection in high-dimensional inference and robustness of adaptive statistical association testing. AMAT first alleviates the burden of noise accumulation via distance correlation learning, and then conducts a data-adaptive association test under the flexible generalized linear model framework. Extensive simulation studies and real data applications demonstrate that AMAT is highly robust and often more powerful than several existing methods, while preserving the correct type I error rate. A free implementation of AMAT in R computing environment is available at https://github.com/kzb193/AMAT.}, }
@article {pmid35046908, year = {2021}, author = {Hammerl, JA and Barac, A and Bienert, A and Demir, A and Drüke, N and Jäckel, C and Matthies, N and Jun, JW and Skurnik, M and Ulrich, J and Hertwig, S}, title = {Birds Kept in the German Zoo "Tierpark Berlin" Are a Common Source for Polyvalent Yersinia pseudotuberculosis Phages.}, journal = {Frontiers in microbiology}, volume = {12}, number = {}, pages = {634289}, pmid = {35046908}, issn = {1664-302X}, abstract = {Yersinia pseudotuberculosis is an important animal pathogen, particularly for birds, rodents, and monkeys, which is also able to infect humans. Indeed, an increasing number of reports have been published on zoo animals that were killed by this species. One option to treat diseased animals is the application of strictly lytic (virulent) phages. However, thus far relatively few phages infecting Y. pseudotuberculosis have been isolated and characterized. To determine the prevalence of Y. pseudotuberculosis phages in zoo animals, fecal samples of birds and some primates, maras, and peccaries kept in the Tierpark Berlin were analyzed. Seventeen out of 74 samples taken in 2013 and 2017 contained virulent phages. The isolated phages were analyzed in detail and could be allocated to three groups. The first group is composed of 10 T4-like phages (PYps2T taxon group: Myoviridae; Tevenvirinae; Tequatrovirus), the second group (PYps23T taxon group: Chaseviridae; Carltongylesvirus; Escherichia virus ST32) consists of five phages encoding a podovirus-like RNA polymerase that is related to an uncommon genus of myoviruses (e.g., Escherichia coli phage phiEcoM-GJ1), while the third group is comprised of two podoviruses (PYps50T taxon group: Autographiviridae; Studiervirinae; Berlinvirus) which are closely related to T7. The host range of the isolated phages differed significantly. Between 5.5 and 86.7% of 128 Y. pseudotuberculosis strains belonging to 20 serotypes were lysed by each phage. All phages were additionally able to lyse Y. enterocolitica B4/O:3 strains, when incubated at 37°C. Some phages also infected Y. pestis strains and even strains belonging to other genera of Enterobacteriaceae. A cocktail containing two of these phages would be able to lyse almost 93% of the tested Y. pseudotuberculosis strains. The study indicates that Y. pseudotuberculosis phages exhibiting a broad-host range can be isolated quite easily from zoo animals, particularly birds.}, }
@article {pmid35042457, year = {2022}, author = {Latino, C and Gianatti, EJ and Mehta, S and Lo, J and Devine, A and Christophersen, C}, title = {Does a high dietary intake of resistant starch affect glycaemic control and alter the gut microbiome in women with gestational diabetes? A randomised control trial protocol.}, journal = {BMC pregnancy and childbirth}, volume = {22}, number = {1}, pages = {46}, pmid = {35042457}, issn = {1471-2393}, support = {Enabling Allied Health Research Capacity 2020//Department of Health, Government of Western Australia/ ; G1005941//Spinnaker Health Research Foundation/ ; }, mesh = {Adult ; Australia/epidemiology ; Diabetes, Gestational/blood/*diet therapy ; Dietary Fiber/*administration &amp; dosage ; Dietary Supplements ; Female ; Gastrointestinal Microbiome/*drug effects ; *Glycemic Control ; Humans ; Linear Models ; Pregnancy ; *Randomized Controlled Trials as Topic ; Resistant Starch/*administration &amp; dosage ; }, abstract = {BACKGROUND: Gestational Diabetes Mellitus (GDM) is prevalent with lasting health implications for the mother and offspring. Medical nutrition therapy is the foundation of GDM management yet achieving optimal glycaemic control often requires treatment with medications, like insulin. New dietary strategies to improve GDM management and outcomes are required. Gut dysbiosis is a feature of GDM pregnancies, therefore, dietary manipulation of the gut microbiota may offer a new avenue for management. Resistant starch is a fermentable dietary fibre known to alter the gut microbiota and enhance production of short-chain fatty acids. Evidence suggests that short-chain fatty acids improve glycaemia via multiple mechanisms, however, this has not been evaluated in GDM.<br><br>METHODS: An open-label, parallel-group design study will investigate whether a high dietary resistant starch intake or resistant starch supplement improves glycaemic control and changes the gut microbiome compared with standard dietary advice in women with newly diagnosed GDM. Ninety women will be randomised to one of three groups - standard dietary treatment for GDM (Control), a high resistant starch diet or a high resistant starch diet plus a 16&#x2009;g resistant starch supplement. Measurements taken at Baseline (24 to 30-weeks' gestation), Day 10 and Day 56 (approximately 36&#x2009;weeks' gestation) will include fasting plasma glucose levels, microbial composition and short-chain fatty acid concentrations in stool, 3-day dietary intake records and bowel symptoms questionnaires. One-week post-natal data collection will include microbial composition and short-chain fatty acid concentrations of maternal and neonatal stools, microbial composition of breastmilk, birthweight, maternal and neonatal outcomes. Mixed model analysis of variance will assess change in glycaemia and permutation-based multivariate analysis of variance will assess changes in microbial composition within and between intervention groups. Distance-based linear modelling will identify correlation between change in stool microbiota, short-chain fatty acids and measures of glycaemia.<br><br>DISCUSSION: To improve outcomes for GDM dyads, evaluation of a high dietary intake of resistant starch to improve glycaemia through the gut microbiome needs to be established. This will expand the dietary interventions available to manage GDM without medication.<br><br>TRIAL REGISTRATION: Australian New Zealand Clinical Trial Registry, ACTRN12620000968976p . Registered 28 September 2020.}, }
@article {pmid35042114, year = {2022}, author = {Ruiz-Rico, M and Renwick, S and Allen-Vercoe, E and Barat, JM}, title = {In vitro susceptibility of human gut microbes to potential food preservatives based on immobilized phenolic compounds.}, journal = {Food chemistry}, volume = {378}, number = {}, pages = {132136}, doi = {10.1016/j.foodchem.2022.132136}, pmid = {35042114}, issn = {1873-7072}, mesh = {*Actinobacteria/genetics ; Bacteroidetes/genetics ; Food Preservatives ; *Gastrointestinal Microbiome ; Humans ; *Microbiota ; RNA, Ribosomal, 16S ; }, abstract = {The development of novel food preservatives based on natural antimicrobials such as phenolic compounds is increasing, but their safety should be established before use, including evaluating their impact on the gut microbiota. This work explored the influence of antimicrobial phenolics presented in different forms on selected human gut microbiota members through in vitro susceptibility tests. The bacteria tested exhibited a wide range of susceptibilities to phenolics depending on the molecule structure and mode of administration. Agathobacter rectalis and Clostridium spiroforme, members of the phylum Firmicutes, were the most sensitive strains. Susceptibility was strain- and species-specific, suggesting that it may not be possible to easily extrapolate results across the human microbiome in general. Species of other phyla including Bacteroidetes, Actinobacteria, Proteobacteria and Verrucomicrobia were more resistant than Firmicutes, with growth of some strains even enhanced. Our results provide insights into the biocompatibility of free and immobilized phenolics as potential food additives.}, }
@article {pmid35040024, year = {2022}, author = {Mulpuru, V and Mishra, N}, title = {Antimicrobial Peptides from Human Microbiome Against Multidrug Efflux Pump of Pseudomonas aeruginosa: a Computational Study.}, journal = {Probiotics and antimicrobial proteins}, volume = {14}, number = {1}, pages = {180-188}, pmid = {35040024}, issn = {1867-1314}, mesh = {Anti-Bacterial Agents/metabolism/pharmacology ; Antimicrobial Peptides ; Bacterial Outer Membrane Proteins/metabolism ; Humans ; Membrane Transport Proteins/metabolism ; Microbial Sensitivity Tests ; *Microbiota ; *Pseudomonas aeruginosa/metabolism ; }, abstract = {The excess use of antibiotics has led to the evolution of multidrug-resistant pathogenic strains causing worldwide havoc. These multidrug-resistant strains require potent inhibitors. Pseudomonas aeruginosa is a lead cause of nosocomial infections and also feature in the critical priority list of the world health organization (WHO) for the development of new antibiotics against their antimicrobial resistance. Antimicrobial peptides (AMPs) found in almost every life form from microorganisms to humans are known to defend their hosts against various pathogens. Owing to the diversity of the human microbiome, in this study, we have identified the cell-penetrating AMPs from the human microbiome and studied their inhibitory activity against the outer membrane protein OprM of the MexAB-OprM, a constitutively expressed multidrug efflux pump of the Ps. aeruginosa. Screening of the AMPs from the human microbiome resulted in the identification of 147 cell-penetrating AMPs (CPAMPs). The virtual screening of these CPAMPs against the OprM protein showed significant inhibitory results with the top docked AMP showing binding affinity exceeding -30 kcal/mol. The molecular dynamic simulation determined the interaction stabilities between the AMPs and the OprM at the binding site. Further, the residue interaction networks (RINs) are analyses to identify the inhibitory patterns. Later, these patterns were confirmed by MM-PBSA analysis suggesting that the AMPs are majorly stabilized by electrostatic interactions at the binding site. Thus, the high binding affinity and insights from the molecular interaction signify that the identified CPAMPs from the human microbiome can be further explored as inhibitory agents against multidrug-resistant Ps. aeruginosa.}, }
@article {pmid35039534, year = {2022}, author = {Lee, SJ and Rho, M}, title = {Multimodal deep learning applied to classify healthy and disease states of human microbiome.}, journal = {Scientific reports}, volume = {12}, number = {1}, pages = {824}, pmid = {35039534}, issn = {2045-2322}, support = {2017M3A9F3041232//National Research Foundation of Korea/ ; 2020-0-01373//Institute of Information &amp; Communications Technology Planning &amp; Evaluation (IITP)/ ; }, mesh = {Colorectal Neoplasms/diagnosis/*microbiology ; *Deep Learning ; Diabetes Mellitus, Type 2/diagnosis/*microbiology ; Genome, Microbial/*genetics ; *Healthy Volunteers ; Humans ; Inflammatory Bowel Diseases/diagnosis/*microbiology ; Liver Cirrhosis/diagnosis/*microbiology ; Metagenome/*genetics ; Metagenomics/*methods ; Microbiota/*genetics ; }, abstract = {Metagenomic sequencing methods provide considerable genomic information regarding human microbiomes, enabling us to discover and understand microbial diseases. Compositional differences have been reported between patients and healthy people, which could be used in the diagnosis of patients. Despite significant progress in this regard, the accuracy of these tools needs to be improved for applications in diagnostics and therapeutics. MDL4Microbiome, the method developed herein, demonstrated high accuracy in predicting disease status by using various features from metagenome sequences and a multimodal deep learning model. We propose combining three different features, i.e., conventional taxonomic profiles, genome-level relative abundance, and metabolic functional characteristics, to enhance classification accuracy. This deep learning model enabled the construction of a classifier that combines these various modalities encoded in the human microbiome. We achieved accuracies of 0.98, 0.76, 0.84, and 0.97 for predicting patients with inflammatory bowel disease, type 2 diabetes, liver cirrhosis, and colorectal cancer, respectively; these are comparable or higher than classical machine learning methods. A deeper analysis was also performed on the resulting sets of selected features to understand the contribution of their different characteristics. MDL4Microbiome is a classifier with higher or comparable accuracy compared with other machine learning methods, which offers perspectives on feature generation with metagenome sequences in deep learning models and their advantages in the classification of host disease status.}, }
@article {pmid35024099, year = {2022}, author = {Pettersen, VK and Antunes, LCM and Dufour, A and Arrieta, MC}, title = {Inferring early-life host and microbiome functions by mass spectrometry-based metaproteomics and metabolomics.}, journal = {Computational and structural biotechnology journal}, volume = {20}, number = {}, pages = {274-286}, pmid = {35024099}, issn = {2001-0370}, abstract = {Humans have a long-standing coexistence with microorganisms. In particular, the microbial community that populates the human gastrointestinal tract has emerged as a critical player in governing human health and disease. DNA and RNA sequencing techniques that map taxonomical composition and genomic potential of the gut community have become invaluable for microbiome research. However, deriving a biochemical understanding of how activities of the gut microbiome shape host development and physiology requires an expanded experimental design that goes beyond these approaches. In this review, we explore advances in high-throughput techniques based on liquid chromatography-mass spectrometry. These omics methods for the identification of proteins and metabolites have enabled direct characterisation of gut microbiome functions and the crosstalk with the host. We discuss current metaproteomics and metabolomics workflows for producing functional profiles, the existing methodological challenges and limitations, and recent studies utilising these techniques with a special focus on early life gut microbiome.}, }
@article {pmid35019670, year = {2022}, author = {Klopp, J and Ferretti, P and Meyer, CU and Hilbert, K and Haiß, A and Marißen, J and Henneke, P and Hudalla, H and Pirr, S and Viemann, D and Zemlin, M and Forslund, SK and Härtel, C and Bork, P and Gehring, S and Van Rossum, T and , }, title = {Meconium Microbiome of Very Preterm Infants across Germany.}, journal = {mSphere}, volume = {7}, number = {1}, pages = {e0080821}, pmid = {35019670}, issn = {2379-5042}, mesh = {Adult ; Bacteria/genetics ; Bifidobacterium/genetics ; Germany ; Humans ; Infant ; Infant, Newborn ; Infant, Premature ; *Meconium/microbiology ; *Microbiota ; RNA, Ribosomal, 16S/genetics ; }, abstract = {Meconium constitutes infants' first bowel movements postnatally. The consistency and microbial load of meconium are different from infant and adult stool. While recent evidence suggests that meconium is sterile in utero, rapid colonization occurs after birth. The meconium microbiome has been associated with negative health outcomes, but its composition is not well described, especially in preterm infants. Here, we characterized the meconium microbiomes from 330 very preterm infants (gestational ages 28 to 32 weeks) from 15 hospitals in Germany and in fecal samples from a subset of their mothers (N = 217). Microbiome profiles were compiled using 16S rRNA gene sequencing with negative and positive controls. The meconium microbiome was dominated by Bifidobacterium, Staphylococcus, and Enterococcus spp. and was associated with gestational age at birth and age at sample collection. Bifidobacterial abundance was negatively correlated with potentially pathogenic genera. The amount of bacterial DNA in meconium samples varied greatly across samples and was associated with the time since birth but not with gestational age or hospital site. In samples with low bacterial load, human mitochondrial sequences were highly amplified using commonly used, bacterial-targeted 16S rRNA primers. Only half of the meconium samples contained sufficient bacterial material to study the microbiome using a standard approach. To facilitate future meconium studies, we present a five-level scoring system ("MecBac") that predicts the success of 16S rRNA bacterial sequencing for meconium samples. These findings provide a foundational characterization of an understudied portion of the human microbiome and will aid the design of future meconium microbiome studies. IMPORTANCE Meconium is present in the intestines of infants before and after birth and constitutes their first bowel movements postnatally. The consistency, composition and microbial load of meconium is largely different from infant and adult stool. While recent evidence suggests that meconium is sterile in utero, rapid colonization occurs after birth. The meconium microbiome has been associated with short-term and long-term negative health outcomes, but its composition is not yet well described, especially in preterm infants. We provide a characterization of the microbiome structure and composition of infant meconium and maternal feces from a large study cohort and propose a method to evaluate meconium samples for bacterial sequencing suitability. These findings provide a foundational characterization of an understudied portion of the human microbiome and will aid the design of future meconium microbiome studies.}, }
@article {pmid35017199, year = {2022}, author = {Chen, C and Liao, J and Xia, Y and Liu, X and Jones, R and Haran, J and McCormick, B and Sampson, TR and Alam, A and Ye, K}, title = {Gut microbiota regulate Alzheimer's disease pathologies and cognitive disorders via PUFA-associated neuroinflammation.}, journal = {Gut}, volume = {71}, number = {11}, pages = {2233-2252}, pmid = {35017199}, issn = {1468-3288}, support = {P30 AG066511/AG/NIA NIH HHS/United States ; R01 AG065177/AG/NIA NIH HHS/United States ; RF1 AG067483/AG/NIA NIH HHS/United States ; UL1 TR002378/TR/NCATS NIH HHS/United States ; K23 AG057790/AG/NIA NIH HHS/United States ; R56 DK136728/DK/NIDDK NIH HHS/United States ; K01 DK114391/DK/NIDDK NIH HHS/United States ; P20 GM130456/GM/NIGMS NIH HHS/United States ; }, mesh = {*Alzheimer Disease/metabolism ; Animals ; Cognition ; Disease Models, Animal ; Dysbiosis ; Fatty Acids, Unsaturated ; *Gastrointestinal Microbiome/physiology ; Humans ; Inflammation/metabolism ; Insulin-Like Growth Factor I ; *Insulins ; Mice ; Neuroinflammatory Diseases ; Plaque, Amyloid/pathology ; RNA, Ribosomal, 16S ; }, abstract = {OBJECTIVE: This study is to investigate the role of gut dysbiosis in triggering inflammation in the brain and its contribution to Alzheimer's disease (AD) pathogenesis.<br><br>DESIGN: We analysed the gut microbiota composition of 3&#xd7;Tg mice in an age-dependent manner. We generated germ-free 3&#xd7;Tg mice and recolonisation of germ-free 3&#xd7;Tg mice with fecal samples from both patients with AD and age-matched healthy donors.<br><br>RESULTS: Microbial 16S rRNA sequencing revealed Bacteroides enrichment. We found a prominent reduction of cerebral amyloid-&#x3b2; plaques and neurofibrillary tangles pathology in germ-free 3&#xd7;Tg mice as compared with specific-pathogen-free mice. And hippocampal RNAseq showed that inflammatory pathway and insulin/IGF-1 signalling in 3&#xd7;Tg mice brain are aberrantly altered in the absence of gut microbiota. Poly-unsaturated fatty acid metabolites identified by metabolomic analysis, and their oxidative enzymes were selectively elevated, corresponding with microglia activation and inflammation. AD patients' gut microbiome exacerbated AD pathologies in 3&#xd7;Tg mice, associated with C/EBP&#x3b2;/asparagine endopeptidase pathway activation and cognitive dysfunctions compared with healthy donors' microbiota transplants.<br><br>CONCLUSIONS: These findings support that a complex gut microbiome is required for behavioural defects, microglia activation and AD pathologies, the gut microbiome contributes to pathologies in an AD mouse model and that dysbiosis of the human microbiome might be a risk factor for AD.}, }
@article {pmid35015907, year = {2022}, author = {Amar, Y and Schneider, E and Köberle, M and Seeholzer, T and Musiol, S and Hölge, IM and Gschwendtner, S and Krappmann, D and Steiger, K and Biedermann, T and Schmidt-Weber, CB and Alessandrini, F}, title = {Microbial dysbiosis in a mouse model of atopic dermatitis mimics shifts in human microbiome and correlates with the key pro-inflammatory cytokines IL-4, IL-33 and TSLP.}, journal = {Journal of the European Academy of Dermatology and Venereology : JEADV}, volume = {36}, number = {5}, pages = {705-716}, doi = {10.1111/jdv.17911}, pmid = {35015907}, issn = {1468-3083}, support = {22011215//Federal Ministry of Food and Agriculture/ ; //Deutsche Forschungsgemeinschaft/ ; }, mesh = {Animals ; Bacteria ; Cytokines ; *Dermatitis, Atopic ; Disease Models, Animal ; Dysbiosis/chemically induced ; Humans ; Interleukin-33 ; Interleukin-4 ; Mice ; *Microbiota ; Oxazolone/adverse effects ; Skin ; }, abstract = {BACKGROUND: Cutaneous bacterial dysbiosis is a characteristic hallmark of atopic dermatitis (AD), and it decisively influences the severity of the disease. Despite this, frequently used murine models of AD have not been characterized regarding the changes in skin microbiome communities.<br><br>OBJECTIVE: To analyse the skin microbiome of two frequently used murine models for AD for assessing their applicability in translational research.<br><br>METHODS: AD was induced in mice by topical application of calcipotriol or oxazolone. Following comparable elicitation of AD-like dermatitis, including IgE induction, the skin microbial communities were analysed and compared with human AD.<br><br>RESULTS: We detected critical differences in the microbiota composition of diseased skin. In contrast to calcipotriol treatment, application of oxazolone induced significant changes in the cutaneous microbiota and a drastic drop of bacterial richness. Furthermore, an expansion of Staphylococci, particularly S.&#x2009;xylosus, was observed in the oxazolone group, also displaying positive correlations with AD key markers including pH, TEWL, IL-4, TSLP and IL-33.<br><br>CONCLUSIONS: In this article, we show that (a) the model of choice to investigate AD needs to be characterized for the cutaneous microbiota if applicable and (b) the oxazolone-mediated mixed Th1-Th2 immune response triggers microbiota-induced alterations which share similarities to dysbiosis in human AD and represents therefore a suitable model for translational research on AD if alterations of the microbiome are in the focus of the investigation.}, }
@article {pmid35008909, year = {2022}, author = {Popkov, VA and Zharikova, AA and Demchenko, EA and Andrianova, NV and Zorov, DB and Plotnikov, EY}, title = {Gut Microbiota as a Source of Uremic Toxins.}, journal = {International journal of molecular sciences}, volume = {23}, number = {1}, pages = {}, pmid = {35008909}, issn = {1422-0067}, support = {21-75-30009//Russian Science Foundation/ ; }, mesh = {Animals ; Bacteria/metabolism ; Cluster Analysis ; Enzymes/metabolism ; *Gastrointestinal Microbiome ; Humans ; Metadata ; RNA, Messenger/genetics/metabolism ; Uremic Toxins/*metabolism ; }, abstract = {Uremic retention solutes are the compounds that accumulate in the blood when kidney excretory function is impaired. Some of these compounds are toxic at high concentrations and are usually known as "uremic toxins". The cumulative detrimental effect of uremic toxins results in numerous health problems and eventually mortality during acute or chronic uremia, especially in end-stage renal disease. More than 100 different solutes increase during uremia; however, the exact origin for most of them is still debatable. There are three main sources for such compounds: exogenous ones are consumed with food, whereas endogenous ones are produced by the host metabolism or by symbiotic microbiota metabolism. In this article, we identify uremic retention solutes presumably of gut microbiota origin. We used database analysis to obtain data on the enzymatic reactions in bacteria and human organisms that potentially yield uremic retention solutes and hence to determine what toxins could be synthesized in bacteria residing in the human gut. We selected biochemical pathways resulting in uremic retention solutes synthesis related to specific bacterial strains and revealed links between toxin concentration in uremia and the proportion of different bacteria species which can synthesize the toxin. The detected bacterial species essential for the synthesis of uremic retention solutes were then verified using the Human Microbiome Project database. Moreover, we defined the relative abundance of human toxin-generating enzymes as well as the possibility of the synthesis of a particular toxin by the human metabolism. Our study presents a novel bioinformatics approach for the elucidation of the origin of both uremic retention solutes and uremic toxins and for searching for the most likely human microbiome producers of toxins that can be targeted and used for the therapy of adverse consequences of uremia.}, }
@article {pmid35008631, year = {2021}, author = {Wellington, VNA and Sundaram, VL and Singh, S and Sundaram, U}, title = {Dietary Supplementation with Vitamin D, Fish Oil or Resveratrol Modulates the Gut Microbiome in Inflammatory Bowel Disease.}, journal = {International journal of molecular sciences}, volume = {23}, number = {1}, pages = {}, pmid = {35008631}, issn = {1422-0067}, support = {DK108054/NH/NIH HHS/United States ; DK067420/NH/NIH HHS/United States ; P20GM121299/NH/NIH HHS/United States ; BX003443//United States Department of Veterans Affairs/ ; }, mesh = {Animals ; *Dietary Supplements ; Fish Oils/pharmacology/*therapeutic use ; *Gastrointestinal Microbiome/drug effects ; Humans ; Inflammatory Bowel Diseases/*drug therapy/*microbiology/pathology ; Resveratrol/pharmacology/*therapeutic use ; Vitamin D/pharmacology/*therapeutic use ; }, abstract = {Gastrointestinal health is influenced by the functional genes and metabolites generated by the human microbiome. As the volume of current biomedical and translational research indicates, the importance and impact of this ecosystem of microorganisms, especially those comprising the gut microbiome on human health, has become increasingly apparent. Changes to the gut microbiome are associated with inflammatory bowel disease (IBD), which is characterized by persistent intestinal inflammation. Furthermore, the lifetime dietary choices of their host may positively or negatively affect both the gut microbiome and its impact on IBD. As such, "anti-inflammatory" dietary supplements, their impact, and mechanisms in restoring gut microbiota homeostasis during IBD is an area of intensive research. Dietary supplementation may represent an important adjuvant treatment avenue for limiting intestinal inflammation in IBD. Overall, this review addresses the development of the gut microbiome, the significance of the gut microbiome in IBD, and the use of dietary supplements such as vitamin D, fish oil, and resveratrol in the mitigation of IBD-associated gut dysbiosis and intestinal inflammation.}, }
@article {pmid35008605, year = {2021}, author = {Vitale, SG and Ferrari, F and Ciebiera, M and Zgliczyńska, M and Rapisarda, AMC and Vecchio, GM and Pino, A and Angelico, G and Knafel, A and Riemma, G and De Franciscis, P and Cianci, S}, title = {The Role of Genital Tract Microbiome in Fertility: A Systematic Review.}, journal = {International journal of molecular sciences}, volume = {23}, number = {1}, pages = {}, pmid = {35008605}, issn = {1422-0067}, mesh = {Cervix Uteri/microbiology ; Endometrium/microbiology ; Female ; Genitalia, Female/*microbiology ; Humans ; Infertility, Female/*microbiology ; *Lactobacillus ; *Microbiota ; Vagina/microbiology ; }, abstract = {The human microbiome plays a crucial role in determining the health status of every human being, and the microbiome of the genital tract can affect the fertility potential before and during assisted reproductive treatments (ARTs). This review aims to identify and appraise studies investigating the correlation of genital microbiome to infertility. Publications up to February 2021 were identified by searching the electronic databases PubMed/MEDLINE, Scopus and Embase and bibliographies. Only full-text original research articles written in English were considered eligible for analysis, whereas reviews, editorials, opinions or letters, case studies, conference papers, and abstracts were excluded. Twenty-six articles were identified. The oldest studies adopted the exclusive culture-based technique, while in recent years PCR and RNA sequencing based on 16S rRNA were the most used technique. Regardless of the anatomical site under investigation, the Lactobacillus-dominated flora seems to play a pivotal role in determining fertility, and in particular Lactobacillus crispatus showed a central role. Nonetheless, the presence of pathogens in the genital tract, such as Chlamydia trachomatis, Gardnerella vaginalis, Ureaplasma species, and Gram-negative stains microorganism, affected fertility also in case of asymptomatic bacterial vaginosis (BV). We failed to identify descriptive or comparative studies regarding tubal microbiome. The microbiome of the genital tract plays a pivotal role in fertility, also in case of ARTs. The standardization of the sampling methods and investigations approaches is warranted to stratify the fertility potential and its subsequent treatment. Prospective tubal microbiome studies are warranted.}, }
@article {pmid35005176, year = {2021}, author = {McGee, JS and Huttenhower, C}, title = {Of mice and men and women: Sexual dimorphism of the gut microbiome.}, journal = {International journal of women's dermatology}, volume = {7}, number = {5Part A}, pages = {533-538}, pmid = {35005176}, issn = {2352-6475}, abstract = {The gut microbiome plays a critical role in developing and educating our immune system. Therefore, its now well-established role in autoimmunity and immune disorders is in some ways not surprising. However, it is well-documented in the literature that there is a female predisposition to autoimmune disorders, while sexual dimorphisms in the human microbiome have been confined largely to areas outside of the gut. Herein, we will review the evidence of sexual dimorphism in the gut microbiome in both mice and humans, how this differs in animal models versus humans, and how such dimorphisms may be established and influenced by both host and environmental factors. We will conclude with a discussion on how these aspects of the gut microbiome may contribute to both the study and pathogenesis of gender-specific autoimmunity and immune disorders.}, }
@article {pmid34995772, year = {2022}, author = {Barlaam, A and Putignani, L and Pane, S and Bianchi, PM and Papini, RA and Giangaspero, A}, title = {What's in a child's ear? A case of otomyiasis by Sarcophaga argyrostoma (Diptera, Sarcophagidae).}, journal = {Parasitology international}, volume = {87}, number = {}, pages = {102537}, doi = {10.1016/j.parint.2022.102537}, pmid = {34995772}, issn = {1873-0329}, mesh = {Animals ; Female ; Humans ; Infant ; Larva ; Microscopy/methods ; Myiasis/diagnosis/*parasitology ; Otitis/diagnosis/*parasitology ; Sarcophagidae/*classification/genetics ; }, abstract = {A clinical report of otomyiasis in a 1-year-old girl is reported. A III instar larva of Sarcophaga sp. was microscopically identified and Sarcophaga (Liopygia) argyrostoma (Diptera, Sarcophagidae) was suspected. A molecular method targeting a fragment of the cox1 gene was used to confirm the identity of the specimen. Although myiases are not frequent manifestations in otolaryngology, they should arouse the attention of doctors, social workers and parents dealing with disabled people, the elderly and children. This contribution also highlights the need of combining microscopy and molecular tools to achieve a correct and reliable identification of the specimen/s.}, }
@article {pmid34995483, year = {2022}, author = {Conwill, A and Kuan, AC and Damerla, R and Poret, AJ and Baker, JS and Tripp, AD and Alm, EJ and Lieberman, TD}, title = {Anatomy promotes neutral coexistence of strains in the human skin microbiome.}, journal = {Cell host &amp; microbe}, volume = {30}, number = {2}, pages = {171-182.e7}, pmid = {34995483}, issn = {1934-6069}, support = {DP2 GM140922/GM/NIGMS NIH HHS/United States ; }, mesh = {*Acne Vulgaris/microbiology ; Humans ; *Microbiota ; Propionibacterium acnes/genetics ; Skin/microbiology ; Whole Genome Sequencing ; }, abstract = {What enables strains of the same species to coexist in a microbiome? Here, we investigate whether host anatomy can explain strain co-residence of Cutibacterium acnes, the most abundant species on human skin. We reconstruct on-person evolution and migration using whole-genome sequencing of C. acnes colonies acquired from healthy subjects, including from individual skin pores, and find considerable spatial structure at the level of pores. Although lineages (sets of colonies separated by <100 mutations) with in vitro fitness differences coexist within centimeter-scale regions, each pore is dominated by a single lineage. Moreover, colonies from a pore typically have identical genomes. An absence of adaptive signatures suggests a genotype-independent source of low within-pore diversity. We therefore propose that pore anatomy imposes random single-cell bottlenecks; the resulting population fragmentation reduces competition and promotes coexistence. Our findings suggest that therapeutic interventions involving pore-dwelling species might focus on removing resident populations over optimizing probiotic fitness.}, }
@article {pmid34994112, year = {2022}, author = {Basu, A and Singh, R and Gupta, S}, title = {Bacterial infections in cancer: A bilateral relationship.}, journal = {Wiley interdisciplinary reviews. Nanomedicine and nanobiotechnology}, volume = {14}, number = {3}, pages = {e1771}, doi = {10.1002/wnan.1771}, pmid = {34994112}, issn = {1939-0041}, mesh = {Bacteria ; *Bacterial Infections/drug therapy ; Drug Delivery Systems ; Drug Discovery ; Humans ; Nanomedicine ; Nanotechnology ; *Neoplasms/drug therapy ; Tumor Microenvironment ; }, abstract = {Bacteria share a long commensal relationship with the human body. New findings, however, continue to unravel many complexities associated with this old alliance. In the past decades, the dysbiosis of human microbiome has been linked to tumorigenesis, and more recently to spontaneous colonization of existing tumors. The topic, however, remains open for debate as the claims for causative-prevailing dual characteristics of bacteria are mostly based on epidemiological evidence rather than robust mechanistic models. There are also no reviews linking the collective impact of bacteria in tumor microenvironments to the efficacy of cancer drugs, mechanisms of pathogen-initiated cancer and bacterial colonization, personalized nanomedicine, nanotechnology, and antimicrobial resistance. In this review, we provide a holistic overview of the bilateral relationship between cancer and bacteria covering all these aspects. Our collated evidence from the literature does not merely categorize bacteria as cancer causative or prevailing agents, but also critically highlights the gaps in the literature where more detailed studies may be required to reach such a conclusion. Arguments are made in favor of dual drug therapies that can simultaneously co-target bacteria and cancer cells to overcome drug resistance. Also discussed are the opportunities for leveraging the natural colonization and remission power of bacteria for cancer treatment. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Infectious Disease Nanotechnology Approaches to Biology > Nanoscale Systems in Biology Therapeutic Approaches and Drug Discovery > Emerging Technologies.}, }
@article {pmid34992297, year = {2022}, author = {Pruss, KM and Enam, F and Battaglioli, E and DeFeo, M and Diaz, OR and Higginbottom, SK and Fischer, CR and Hryckowian, AJ and Van Treuren, W and Dodd, D and Kashyap, P and Sonnenburg, JL}, title = {Oxidative ornithine metabolism supports non-inflammatory C. difficile colonization.}, journal = {Nature metabolism}, volume = {4}, number = {1}, pages = {19-28}, pmid = {34992297}, issn = {2522-5812}, support = {K08 DK110335/DK/NIDDK NIH HHS/United States ; R01 DK085025/DK/NIDDK NIH HHS/United States ; T32 AI007328/AI/NIAID NIH HHS/United States ; }, mesh = {Amino Acids/metabolism ; Animals ; Clostridioides difficile/*physiology ; Clostridium Infections/*metabolism/*microbiology ; Energy Metabolism ; Gastrointestinal Microbiome ; *Host-Pathogen Interactions ; Humans ; Metabolic Networks and Pathways ; Metabolome ; Metabolomics/methods ; Mice ; Nitric Oxide Synthase/metabolism ; Ornithine/*metabolism ; *Oxidation-Reduction ; Oxidative Stress ; }, abstract = {The enteric pathogen Clostridioides difficile (Cd) is responsible for a toxin-mediated infection that causes more than 200,000 recorded hospitalizations and 13,000 deaths in the United States every year[1]. However, Cd can colonize the gut in the absence of disease symptoms. Prevalence of asymptomatic colonization by toxigenic Cd in healthy populations is high; asymptomatic carriers are at increased risk of infection compared to noncolonized individuals and may be a reservoir for transmission of Cd infection[2,3]. Elucidating the molecular mechanisms by which Cd persists in the absence of disease is necessary for understanding pathogenesis and developing refined therapeutic strategies. Here, we show with gut microbiome metatranscriptomic analysis that mice recalcitrant to Cd infection and inflammation exhibit increased community-wide expression of arginine and ornithine metabolic pathways. To query Cd metabolism specifically, we leverage RNA sequencing in gnotobiotic mice infected with two wild-type strains (630 and R20291) and isogenic toxin-deficient mutants of these strains to differentiate inflammation-dependent versus -independent transcriptional states. A single operon encoding oxidative ornithine degradation is consistently upregulated across non-toxigenic Cd strains. Combining untargeted and targeted metabolomics with bacterial and host genetics, we demonstrate that both diet- and host-derived sources of ornithine provide a competitive advantage to Cd, suggesting a mechanism for Cd persistence within a non-inflammatory, healthy gut.}, }
@article {pmid34990774, year = {2022}, author = {Uzoukwu, EU and Phandanouvong-Lozano, V and Usman, H and Sfeir, CS and Niepa, THR}, title = {Droplet-based microsystems as novel assessment tools for oral microbial dynamics.}, journal = {Biotechnology advances}, volume = {55}, number = {}, pages = {107903}, doi = {10.1016/j.biotechadv.2021.107903}, pmid = {34990774}, issn = {1873-1899}, mesh = {Bacteria ; *Dental Caries ; Humans ; Microbial Interactions ; *Microbiota ; Mouth/microbiology ; }, abstract = {The human microbiome comprises thousands of microbial species that live in and on the body and play critical roles in human health and disease. Recent findings on the interplay among members of the oral microbiome, defined by a personalized set of microorganisms, have elucidated the role of bacteria and yeasts in oral health and diseases including dental caries, halitosis, and periodontal infections. However, the majority of these studies rely on traditional culturing methods which are limited in their ability of replicating the oral microenvironment, and therefore fail to evaluate key microbial interactions in microbiome dynamics. Novel culturing methods have emerged to address this shortcoming. Here, we reviewed the potential of droplet-based microfluidics as an alternative approach for culturing microorganisms and assessing the oral microbiome dynamics. We discussed the state of the art and recent progress in the field of oral microbiology. Although at its infancy, droplet-based microtechnology presents an interesting potential for elucidating oral microbial dynamics and pathophysiology. We highlight how new findings provided by current microfluidic-based methodologies could advance the investigation of the oral microbiome. We anticipate that our work involving the droplet-based microfluidic technique with a semipermeable membrane will lay the foundations for future microbial dynamics studies and further expand the knowledge of the oral microbiome and its implication in oral health.}, }
@article {pmid34989907, year = {2022}, author = {Filik, K and Szermer-Olearnik, B and Niedziółka-Jönson, J and Roźniecka, E and Ciekot, J and Pyra, A and Matyjaszczyk, I and Skurnik, M and Brzozowska, E}, title = {φYeO3-12 phage tail fiber Gp17 as a promising high specific tool for recognition of Yersinia enterocolitica pathogenic serotype O:3.}, journal = {AMB Express}, volume = {12}, number = {1}, pages = {1}, pmid = {34989907}, issn = {2191-0855}, support = {National Science Center//Narodowym Centrum Nauki/ ; Poland (Grant Numbers UMO-2017/26/E/NZ1/00249).//Narodowym Centrum Nauki/ ; }, abstract = {Yersiniosis is an infectious zoonotic disease caused by two enteropathogenic species of Gram-negative genus Yersinia: Yersinia enterocolitica and Yersinia pseudotuberculosis. Pigs and other wild and domestic animals are reservoirs for these bacteria. Infection is usually spread to humans by ingestion of contaminated food. Yersiniosis is considered a rare disease, but recent studies indicate that it is overlooked in the diagnostic process therefore the infections with this bacterium are not often identified. Reliable diagnosis of Yersiniosis by culturing is difficult due to the slow growth of the bacteria easily overgrown by other more rapidly growing microbes unless selec-tive growth media is used. Phage adhesins recognizing bacteria in a specific manner can be an excellent diagnostic tool, es-pecially in the diagnosis of pathogens difficult for culturing. In this study, it was shown that Gp17, the tail fiber protein (TFP) of phage φYeO3-12, specifically recognizes only the pathogenic Yersinia enterocolitica serotype O:3 (YeO:3) bacteria. The ELISA test used in this work confirmed the specific interaction of this protein with YeO:3 and demonstrated a promising tool for developing the pathogen recognition method based on phage adhesins.}, }
@article {pmid34985325, year = {2022}, author = {Sorboni, SG and Moghaddam, HS and Jafarzadeh-Esfehani, R and Soleimanpour, S}, title = {A Comprehensive Review on the Role of the Gut Microbiome in Human Neurological Disorders.}, journal = {Clinical microbiology reviews}, volume = {35}, number = {1}, pages = {e0033820}, pmid = {34985325}, issn = {1098-6618}, mesh = {Dysbiosis/metabolism/therapy ; *Gastrointestinal Microbiome/physiology ; Humans ; *Nervous System Diseases/therapy ; Prebiotics ; *Probiotics/therapeutic use ; *Synbiotics ; }, abstract = {The human body is full of an extensive number of commensal microbes, consisting of bacteria, viruses, and fungi, collectively termed the human microbiome. The initial acquisition of microbiota occurs from both the external and maternal environments, and the vast majority of them colonize the gastrointestinal tract (GIT). These microbial communities play a central role in the maturation and development of the immune system, the central nervous system, and the GIT system and are also responsible for essential metabolic pathways. Various factors, including host genetic predisposition, environmental factors, lifestyle, diet, antibiotic or nonantibiotic drug use, etc., affect the composition of the gut microbiota. Recent publications have highlighted that an imbalance in the gut microflora, known as dysbiosis, is associated with the onset and progression of neurological disorders. Moreover, characterization of the microbiome-host cross talk pathways provides insight into novel therapeutic strategies. Novel preclinical and clinical research on interventions related to the gut microbiome for treating neurological conditions, including autism spectrum disorders, Parkinson's disease, schizophrenia, multiple sclerosis, Alzheimer's disease, epilepsy, and stroke, hold significant promise. This review aims to present a comprehensive overview of the potential involvement of the human gut microbiome in the pathogenesis of neurological disorders, with a particular emphasis on the potential of microbe-based therapies and/or diagnostic microbial biomarkers. This review also discusses the potential health benefits of the administration of probiotics, prebiotics, postbiotics, and synbiotics and fecal microbiota transplantation in neurological disorders.}, }
@article {pmid34981957, year = {2022}, author = {Pavletić, B and Runzheimer, K and Siems, K and Koch, S and Cortesão, M and Ramos-Nascimento, A and Moeller, R}, title = {Spaceflight Virology: What Do We Know about Viral Threats in the Spaceflight Environment?.}, journal = {Astrobiology}, volume = {22}, number = {2}, pages = {210-224}, pmid = {34981957}, issn = {1557-8070}, mesh = {Astronauts ; Humans ; *Microbiota ; *Space Flight ; Spacecraft ; *Weightlessness ; }, abstract = {Viruses constitute a significant part of the human microbiome, so wherever humans go, viruses are brought with them, even on space missions. In this mini review, we focus on the International Space Station (ISS) as the only current human habitat in space that has a diverse range of viral genera that infect microorganisms from bacteria to eukaryotes. Thus, we have reviewed the literature on the physical conditions of space habitats that have an impact on both virus transmissibility and interaction with their host, which include UV radiation, ionizing radiation, humidity, and microgravity. Also, we briefly comment on the practices used on space missions that reduce virus spread, that is, use of antimicrobial surfaces, spacecraft sterilization practices, and air filtration. Finally, we turn our attention to the health threats that viruses pose to space travel. Overall, even though efforts are taken to ensure safe conditions during human space travel, for example, preflight quarantines of astronauts, we reflect on the potential risks humans might be exposed to and how those risks might be aggravated in extraterrestrial habitats.}, }
@article {pmid34978141, year = {2022}, author = {Michels, N and Zouiouich, S and Vanderbauwhede, B and Vanacker, J and Indave Ruiz, BI and Huybrechts, I}, title = {Human microbiome and metabolic health: An overview of systematic reviews.}, journal = {Obesity reviews : an official journal of the International Association for the Study of Obesity}, volume = {23}, number = {4}, pages = {e13409}, doi = {10.1111/obr.13409}, pmid = {34978141}, issn = {1467-789X}, support = {001/WHO_/World Health Organization/International ; }, mesh = {*Diabetes Mellitus, Type 2 ; *Gastrointestinal Microbiome ; Humans ; *Microbiota ; *Non-alcoholic Fatty Liver Disease ; Obesity ; *Probiotics ; Systematic Reviews as Topic ; }, abstract = {To summarize the microbiome's role in metabolic disorders (insulin resistance, hyperglycemia, type 2 diabetes, obesity, hyperlipidemia, hypertension, nonalcoholic fatty liver disease [NAFLD], and metabolic syndrome), systematic reviews on observational or interventional studies (prebiotics/probiotics/synbiotics/transplant) were searched in MEDLINE and Embase until September 2020. The 87 selected systematic reviews included 57 meta-analyses. Methodological quality (AMSTAR2) was moderate in 62%, 12% low, and 26% critically low. Observational studies on obesity (10 reviews) reported less gut bacterial diversity with higher Fusobacterium, Lactobacillus reuteri, Bacteroides fragilis, and Staphylococcus aureus, whereas lower Methanobrevibacter, Lactobacillus plantarum, Akkermansia muciniphila, and Bifidobacterium animalis compared with nonobese. For diabetes (n = 1), the same was found for Fusobacterium and A. muciniphila, whereas higher Ruminococcus and lower Faecalibacterium, Roseburia, Bacteroides vulgatus, and several Bifidobacterium spp. For NAFLD (n = 2), lower Firmicutes, Rikenellaceae, Ruminococcaceae, whereas higher Escherichia and Lactobacillus were detected. Discriminating bacteria overlapped between metabolic disorders, those with high abundance being often involved in inflammation, whereas those with low abundance being used as probiotics. Meta-analyses (n = 54) on interventional studies reported 522 associations: 54% was statistically significant with intermediate effect size and moderate between-study heterogeneity. Meta-evidence was highest for probiotics and lowest for fecal transplant. Future avenues include better methodological quality/comparability, testing functional differences, new intervention strategies, and considerating other body habitats and kingdoms.}, }
@article {pmid34978130, year = {2022}, author = {Feng, Y and Bui, TPN and Stams, AJM and Boeren, S and Sánchez-Andrea, I and de Vos, WM}, title = {Comparative genomics and proteomics of Eubacterium maltosivorans: functional identification of trimethylamine methyltransferases and bacterial microcompartments in a human intestinal bacterium with a versatile lifestyle.}, journal = {Environmental microbiology}, volume = {24}, number = {1}, pages = {517-534}, pmid = {34978130}, issn = {1462-2920}, mesh = {Eubacterium ; Humans ; Life Style ; Methylamines ; *Methyltransferases/genetics ; *Proteomics ; }, abstract = {Eubacterium maltosivorans YI[T] is a human intestinal isolate capable of acetogenic, propionogenic and butyrogenic growth. Its 4.3-Mb genome sequence contains coding sequences for 4227 proteins, including 41 different methyltransferases. Comparative proteomics of strain YI[T] showed the Wood-Ljungdahl pathway proteins to be actively produced during homoacetogenic growth on H2 and CO2 while butyrogenic growth on a mixture of lactate and acetate significantly upregulated the production of proteins encoded by the recently identified lctABCDEF cluster and accessory proteins. Growth on H2 and CO2 unexpectedly induced the production of two related trimethylamine methyltransferases. Moreover, a set of 16 different trimethylamine methyltransferases together with proteins for bacterial microcompartments were produced during growth and deamination of the quaternary amines, betaine, carnitine and choline. Growth of strain YI[T] on 1,2-propanediol generated propionate with propanol and induced the formation of bacterial microcompartments that were also prominently visible in betaine-grown cells. The present study demonstrates that E. maltosivorans is highly versatile in converting low-energy fermentation end-products in the human gut into butyrate and propionate whilst being capable of preventing the formation of the undesired trimethylamine by converting betaine and other quaternary amines in bacterial microcompartments into acetate and butyrate.}, }
@article {pmid34975829, year = {2021}, author = {Karisola, P and Palosuo, K and Hinkkanen, V and Wisgrill, L and Savinko, T and Fyhrquist, N and Alenius, H and Mäkelä, MJ}, title = {Integrative Transcriptomics Reveals Activation of Innate Immune Responses and Inhibition of Inflammation During Oral Immunotherapy for Egg Allergy in Children.}, journal = {Frontiers in immunology}, volume = {12}, number = {}, pages = {704633}, pmid = {34975829}, issn = {1664-3224}, mesh = {Administration, Oral ; Adolescent ; Allergens/administration &amp; dosage/therapeutic use ; Antibody Specificity ; Child ; Cytokines/blood ; *Desensitization, Immunologic ; Dose-Response Relationship, Immunologic ; Egg Hypersensitivity/blood/genetics/immunology/*therapy ; Egg Proteins/administration &amp; dosage/adverse effects/*immunology/therapeutic use ; Female ; Gene Expression Regulation ; Gene Ontology ; Genomics/*methods ; Humans ; *Immunity, Innate ; Immunoglobulins/blood ; Inflammation/etiology/immunology/*prevention &amp; control ; Isoantibodies/blood/immunology ; Leukocytes, Mononuclear/*metabolism ; Lymphocyte Count ; Lymphocyte Subsets/immunology ; Male ; *Transcriptome ; Treatment Outcome ; }, abstract = {We previously reported the results of a randomized, open-label trial of egg oral immunotherapy (OIT) in 50 children where 44% were desensitized and 46% were partially desensitized after 8 months of treatment. Here we focus on cell-mediated molecular mechanisms driving desensitization during egg OIT. We sought to determine whether changes in genome-wide gene expression in blood cells during egg OIT correlate with humoral responses and the clinical outcome. The blood cell transcriptome of 50 children receiving egg OIT was profiled using peripheral blood mononuclear cell (PBMC) samples obtained at baseline and after 3 and 8 months of OIT. We identified 467 differentially expressed genes (DEGs) after 3 or 8 months of egg OIT. At 8 months, 86% of the DEGs were downregulated and played a role in the signaling of TREM1, IL-6, and IL-17. In correlation analyses, Gal d 1-4-specific IgG4 antibodies associated positively with DEGs playing a role in pathogen recognition and antigen presentation and negatively with DEGs playing a role in the signaling of IL-10, IL-6, and IL-17. Desensitized and partially desensitized patients had differences in their antibody responses, and although most of the transcriptomic changes were shared, both groups had also specific patterns, which suggest slower changes in partially desensitized and activation of NK cells in the desensitized group. OIT for egg allergy in children inhibits inflammation and activates innate immune responses regardless of the clinical outcome at 8 months. Changes in gene expression patterns first appear as posttranslational protein modifications, followed by more sustained epigenetic gene regulatory functions related to successful desensitization.}, }
@article {pmid34972816, year = {2022}, author = {Ryu, TY and Kim, K and Han, TS and Lee, MO and Lee, J and Choi, J and Jung, KB and Jeong, EJ and An, DM and Jung, CR and Lim, JH and Jung, J and Park, K and Lee, MS and Kim, MY and Oh, SJ and Hur, K and Hamamoto, R and Park, DS and Kim, DS and Son, MY and Cho, HS}, title = {Human gut-microbiome-derived propionate coordinates proteasomal degradation via HECTD2 upregulation to target EHMT2 in colorectal cancer.}, journal = {The ISME journal}, volume = {16}, number = {5}, pages = {1205-1221}, pmid = {34972816}, issn = {1751-7370}, mesh = {*Colorectal Neoplasms ; Histocompatibility Antigens/metabolism ; Histone-Lysine N-Methyltransferase/genetics/metabolism ; Humans ; *Microbiota ; Propionates ; Ubiquitin-Protein Ligases/*metabolism ; Up-Regulation ; }, abstract = {The human microbiome plays an essential role in the human immune system, food digestion, and protection from harmful bacteria by colonizing the human intestine. Recently, although the human microbiome affects colorectal cancer (CRC) treatment, the mode of action between the microbiome and CRC remains unclear. This study showed that propionate suppressed CRC growth by promoting the proteasomal degradation of euchromatic histone-lysine N-methyltransferase 2 (EHMT2) through HECT domain E3 ubiquitin protein ligase 2 (HECTD2) upregulation. In addition, EHMT2 downregulation reduced the H3K9me2 level on the promoter region of tumor necrosis factor α-induced protein 1 (TNFAIP1) as a novel direct target of EHMT2. Subsequently, TNFAIP1 upregulation induced the apoptosis of CRC cells. Furthermore, using Bacteroides thetaiotaomicron culture medium, we confirmed EHMT2 downregulation via upregulation of HECTD2 and TNFAIP1 upregulation. Finally, we observed the synergistic effect of propionate and an EHMT2 inhibitor (BIX01294) in 3D spheroid culture models. Thus, we suggest the anticancer effects of propionate and EHMT2 as therapeutic targets for colon cancer treatment and may provide the possibility for the synergistic effects of an EHMT2 inhibitor and microbiome in CRC treatment.}, }
@article {pmid34970503, year = {2021}, author = {Cardile, S and Del Chierico, F and Candusso, M and Reddel, S and Bernaschi, P and Pietrobattista, A and Spada, M and Torre, G and Putignani, L}, title = {Impact of Two Antibiotic Therapies on Clinical Outcome and Gut Microbiota Profile in Liver Transplant Paediatric Candidates Colonized by Carbapenem-Resistant Klebsiella pneumoniae CR-KP.}, journal = {Frontiers in cellular and infection microbiology}, volume = {11}, number = {}, pages = {730904}, pmid = {34970503}, issn = {2235-2988}, mesh = {Anti-Bacterial Agents/therapeutic use ; Carbapenems/pharmacology ; Child ; *Gastrointestinal Microbiome ; Humans ; Klebsiella ; *Klebsiella Infections/drug therapy/prevention &amp; control ; Klebsiella pneumoniae/genetics ; *Liver Transplantation ; Pilot Projects ; RNA, Ribosomal, 16S/genetics ; }, abstract = {Colonization by multidrug-resistant (MDR) organisms in liver transplant (LT) candidates significantly affects the LT outcome. To date, consensus about patient management is lacking, including microbiological screening indications. This pilot study aimed to evaluate the impact of carbapenem-resistant Klebsiella pneumoniae (CR-KP) colonization in LT paediatric candidates to enable optimal prevention and therapeutic strategies that exploit both clinical and microbiological approaches. Seven paediatric patients colonized by CR-KP were evaluated before and until one-year post LT. At the time of the transplant, patients were stratified based on antibiotic (ATB) prophylaxis into two groups: 'standard ATB' (standard ATB prophylaxis), and 'targeted ATB' (MDR antibiogram-based ATB prophylaxis). Twenty-eight faecal samples were collected during follow-up and used for MDR screening and gut microbiota 16S rRNA-based profiling. Post-transplant hospitalization duration was comparable for both groups. With the exception of one patient, no serious infections and/or complications, nor deaths were recorded. A progressive MDR decontamination was registered. In the 'standard ATB' group, overall bacterial richness increased. Moreover, 6 months after LT, Lactobacillus and Bulleidia were increased and Enterobacteriaceae and Klebsiella spp. were reduced. In the 'targeted ATB' group Klebsiella spp., Ruminococcus gnavus, Erysipelotrichaceae, and Bifidobacterium spp. were increased 12 months after LT. In conclusion, both antibiotics prophylaxis do not affect nor LT outcomes or the risk of intestinal bacterial translocation. However, in the 'standard ATB' group, gut microbiota richness after LT was increased, with an increase of beneficial lactic acid- and short-chain fatty acids (SCFA)-producing bacteria and the reduction of harmful Enterobacteriaceae and Klebsiella spp. It could therefore be appropriate to administer standard prophylaxis, reserving the use of ATB-based molecules only in case of complications.}, }
@article {pmid34969973, year = {2022}, author = {Stankeviciute, G and Tang, P and Ashley, B and Chamberlain, JD and Hansen, MEB and Coleman, A and D'Emilia, R and Fu, L and Mohan, EC and Nguyen, H and Guan, Z and Campopiano, DJ and Klein, EA}, title = {Convergent evolution of bacterial ceramide synthesis.}, journal = {Nature chemical biology}, volume = {18}, number = {3}, pages = {305-312}, pmid = {34969973}, issn = {1552-4469}, support = {U54 GM069338/GM/NIGMS NIH HHS/United States ; R01 AI148366/AI/NIAID NIH HHS/United States ; BB/M010996/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; BB/T016841/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Bacteria/genetics/metabolism ; Biosynthetic Pathways ; *Ceramides/chemistry/metabolism ; Humans ; Phylogeny ; *Sphingolipids/chemistry/metabolism ; }, abstract = {The bacterial domain produces numerous types of sphingolipids with various physiological functions. In the human microbiome, commensal and pathogenic bacteria use these lipids to modulate the host inflammatory system. Despite their growing importance, their biosynthetic pathway remains undefined since several key eukaryotic ceramide synthesis enzymes have no bacterial homolog. Here we used genomic and biochemical approaches to identify six proteins comprising the complete pathway for bacterial ceramide synthesis. Bioinformatic analyses revealed the widespread potential for bacterial ceramide synthesis leading to our discovery of a Gram-positive species that produces ceramides. Biochemical evidence demonstrated that the bacterial pathway operates in a different order from that in eukaryotes. Furthermore, phylogenetic analyses support the hypothesis that the bacterial and eukaryotic ceramide pathways evolved independently.}, }
@article {pmid34969071, year = {2022}, author = {Clausen, DS and Willis, AD}, title = {Evaluating replicability in microbiome data.}, journal = {Biostatistics (Oxford, England)}, volume = {23}, number = {4}, pages = {1099-1114}, pmid = {34969071}, issn = {1468-4357}, support = {R35 GM133420/GM/NIGMS NIH HHS/United States ; T32 ES015459/ES/NIEHS NIH HHS/United States ; }, mesh = {High-Throughput Nucleotide Sequencing/methods ; Humans ; *Microbiota/genetics ; RNA, Ribosomal, 16S/genetics ; }, abstract = {High-throughput sequencing is widely used to study microbial communities. However, choice of laboratory protocol is known to affect the resulting microbiome data, which has an unquantified impact on many comparisons between communities of scientific interest. We propose a novel approach to evaluating replicability in high-dimensional data and apply it to assess the cross-laboratory replicability of signals in microbiome data using the Microbiome Quality Control Project data set. We learn distinctions between samples as measured by a single laboratory and evaluate whether the same distinctions hold in data produced by other laboratories. While most sequencing laboratories can consistently distinguish between samples (median correct classification 87% on genus-level proportion data), these distinctions frequently fail to hold in data from other laboratories (median correct classification 55% across laboratory on genus-level proportion data). As identical samples processed by different laboratories generate substantively different quantitative results, we conclude that 16S sequencing does not reliably resolve differences in human microbiome samples. However, because we observe greater replicability under certain data transformations, our results inform the analysis of microbiome data.}, }
@article {pmid34965174, year = {2022}, author = {Hiippala, K and Khan, I and Ronkainen, A and Boulund, F and Vähä-Mäkilä, H and Suutarinen, M and Seifert, M and Engstrand, L and Satokari, R}, title = {Novel strain of Pseudoruminococcus massiliensis possesses traits important in gut adaptation and host-microbe interactions.}, journal = {Gut microbes}, volume = {14}, number = {1}, pages = {2013761}, pmid = {34965174}, issn = {1949-0984}, mesh = {Adaptation, Physiological ; Bacterial Proteins/genetics/metabolism ; Butyrates/metabolism ; Firmicutes/classification/genetics/*isolation &amp; purification/*physiology ; Gastrointestinal Microbiome ; Genome, Bacterial ; Glycoside Hydrolases/genetics/metabolism ; Host Microbial Interactions ; Humans ; Intestines/*microbiology ; }, abstract = {Fecal microbiota transplantation (FMT) is an efficient treatment for recurrent Clostridioides difficile infection and currently investigated as a treatment for other intestinal and systemic diseases. Better understanding of the species potentially transferred in FMT is needed. We isolated from a healthy fecal donor a novel strain E10-96H of Pseudoruminococcus massiliensis, a recently described strictly anaerobic species currently represented only by the type strain. The whole genome sequence of E10-96H had over 98% similarity with the type strain. E10-96H carries 20 glycoside hydrolase encoding genes, degrades starch in vitro and thus may contribute to fiber degradation, cross-feeding of other species and butyrate production in the intestinal ecosystem. The strain carries pilus-like structures, harbors pilin genes in its genome and adheres to enterocytes in vitro but does not provoke a proinflammatory response. P. massiliensis seems to have commensal behavior with the host epithelium, and its role in intestinal ecology should be studied further.}, }
@article {pmid34964289, year = {2021}, author = {Wise, NM and Wagner, SJ and Worst, TJ and Sprague, JE and Oechsle, CM}, title = {Comparison of swab types for collection and analysis of microorganisms.}, journal = {MicrobiologyOpen}, volume = {10}, number = {6}, pages = {e1244}, pmid = {34964289}, issn = {2045-8827}, mesh = {Bacteriological Techniques/*instrumentation ; DNA, Bacterial/*analysis/isolation &amp; purification ; Humans ; *Microbiota ; Proteus mirabilis/genetics/*isolation &amp; purification ; Real-Time Polymerase Chain Reaction ; Specimen Handling/*instrumentation ; }, abstract = {The human microbiome has begun to emerge as a potential forensic tool, with varied applications ranging from unique identification to investigative leads that link individuals and/or locations. The relative abundance of the combined DNA of the microbiome, compared to human nuclear DNA, may expand potential sources of biological evidence, especially in cases with transfer or low-copy number DNA samples. This work sought to determine the optimal swab type for the collection and analysis of microorganisms. A bacterium (Proteus mirabilis) was deposited by pipette onto four swab types (cotton, flocked, dental applicators, and dissolvable), and extraction and real-time PCR quantitation of the bacterial DNA were performed, which allowed for absolute microbial DNA recovery and comparison of yields across the four sampling substrates. Flocked swabs had the highest yield (~1240 ng) compared to the cotton swabs (~184 ng), dental applicators (~533 ng), and dissolvable swabs (~430 ng). The collection efficiency was further evaluated for cotton and flocked swabs using dried microbial samples spotted onto non-porous surfaces (treated wood, glass, plastic, and tile). Flocked swabs performed consistently better across wood, glass, and tile, but showed decreased recovery from plastic. The cotton swabs failed in the recovery of P. mirabilis DNA across all surfaces. Knowing the appropriate sampling substrate will be useful as others continue to investigate the use of the microbiome as a forensics tool.}, }
@article {pmid34963470, year = {2021}, author = {Jang, HJ and Choi, JY and Kim, K and Yong, SH and Kim, YW and Kim, SY and Kim, EY and Jung, JY and Kang, YA and Park, MS and Kim, YS and Cho, YJ and Lee, SH}, title = {Relationship of the lung microbiome with PD-L1 expression and immunotherapy response in lung cancer.}, journal = {Respiratory research}, volume = {22}, number = {1}, pages = {322}, pmid = {34963470}, issn = {1465-993X}, support = {2018R1C1B5043991//National Research Foundation of Korea/ ; 14-2016-011//Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul National University Bundang Hospital/ ; }, mesh = {Aged ; Antineoplastic Agents, Immunological ; B7-H1 Antigen/*biosynthesis/genetics ; Biomarkers, Tumor/biosynthesis/genetics ; Carcinoma, Non-Small-Cell Lung/genetics/*metabolism/therapy ; Female ; Gene Expression Regulation, Neoplastic/*physiology ; Humans ; Immunotherapy/*methods ; Lung/metabolism/microbiology/pathology ; Lung Neoplasms/genetics/*metabolism/therapy ; Male ; Microbiota/*physiology ; Middle Aged ; Prospective Studies ; }, abstract = {BACKGROUND: Lung cancer is the primary cause of cancer-related deaths worldwide. The human lung serves as a niche to a unique and dynamic bacterial community that is related to the development of multiple diseases. Here, we investigated the differences in the lung microbiomes of patients with lung cancer.<br><br>METHODS: 16S rRNA sequencing was performed to evaluate the respiratory tract microbiome present in the bronchoalveolar lavage fluid. Patients were stratified based on programmed death-ligand 1 (PD-L1) expression levels and immunotherapy responses.<br><br>RESULTS: In total, 84 patients were prospectively analyzed, of which 59 showed low (<&#x2009;10%), and 25 showed high (&#x2265;&#x2009;10%) PD-L1 expression levels. The alpha and beta diversities did not significantly differ between the two groups. Veillonella dispar was dominant in the high-PD-L1 group; the population of Neisseria was significantly higher in the low-PD-L1 group than in the high-PD-L1 group. In the immunotherapy responder group, V. dispar was dominant, while Haemophilus influenzae and Neisseria perflava were dominant in the non-responder group.<br><br>CONCLUSION: The abundances of Neisseria and V. dispar differed significantly in relation to PD-L1 expression levels and immunotherapy responses.}, }
@article {pmid34963427, year = {2022}, author = {Fromentin, M and Bridier-Nahmias, A and Legoff, J and Mercier-Delarue, S and Ranger, N and Vuillard, C and Do Vale, J and Zucman, N and Alberdi, A and Ricard, JD and Roux, D}, title = {The 16S rRNA lung microbiome in mechanically ventilated patients: a methodological study.}, journal = {Experimental lung research}, volume = {48}, number = {1}, pages = {23-34}, doi = {10.1080/01902148.2021.2021327}, pmid = {34963427}, issn = {1521-0499}, mesh = {Bacteria/genetics ; High-Throughput Nucleotide Sequencing/methods ; Humans ; Lung ; *Microbiota/genetics ; RNA, Ribosomal, 16S/genetics ; *Respiration, Artificial/adverse effects ; }, abstract = {Characterization of the respiratory tract bacterial microbiome is in its infancy when compared to the gut microbiota. To limit bias mandates a robust methodology. Specific amplification of the hypervariable (V) region of the 16SrRNA gene is a crucial step. Differences in accuracy exist for one V region to another depending on the sampled environment. We aimed to assess the impact of the primer sequences targeting the V4 region currently used for gut microbiota studies in respiratory samples. Materials and methods: The original 515 F-806R primer pair targets the V4 region of the 16SrRNA gene. We compared two different 515 F-806R primer pairs before Illumina 250 paired-end sequencing for bacterial microbiome analyses of respiratory samples from critically-ill ventilated patients. "S-V4" for "Stringent V4" primer pair is used in two ongoing international projects "the Integrative Human microbiome project (iHMP)" and "the Earth microbiome project (EMP)." "R-V4" for "Relaxed V4" primer pair has been modified to reduce biases against specific environmental taxa. The optimal method was determined by concordance with conventional microbiology. Results: Twenty samples from three patients who developed a ventilator-associated pneumonia (VAP) and four who did not (control ventilated patients) were sequenced. Highly different results were obtained. "S-V4" provided the best agreement with the conventional microbiology for endotracheal aspirate: 89% as compared to 56% for "R-V4." The main difference related to poor Enterobacteriaceae detection with "R-V4" primers. Conclusions: Accuracy of the bacterial lung microbiome composition was highly dependent on the primers used for amplification of the 16 s rRNA hypervariable sequence. This work validates for future lung microbiome studies the use of the 515 F-806R "S-V4" primer pair associated to Illumina® MiSeq paired-end sequencing.}, }
@article {pmid34960092, year = {2021}, author = {Fierro, V and Marzano, V and Monaci, L and Vernocchi, P and Mennini, M and Valluzzi, R and Levi Mortera, S and Pilolli, R and Dahdah, L and Calandrelli, V and Bracaglia, G and Arasi, S and Riccardi, C and Fiocchi, A and Putignani, L}, title = {Threshold of Reactivity and Tolerance to Precautionary Allergen-Labelled Biscuits of Baked Milk- and Egg-Allergic Children.}, journal = {Nutrients}, volume = {13}, number = {12}, pages = {}, pmid = {34960092}, issn = {2072-6643}, support = {Ricerca Corrente 2018//Ministero della Salute/ ; ad hoc//Galbusera/ ; }, mesh = {Adolescent ; Allergens/*analysis ; Child ; Child, Preschool ; Egg Hypersensitivity/etiology/*immunology/*prevention &amp; control ; Egg Proteins/analysis/immunology ; Female ; Food Analysis/methods ; *Food Labeling ; Humans ; Infant ; Male ; Mass Spectrometry ; Milk Hypersensitivity/etiology/*immunology/*prevention &amp; control ; Milk Proteins/analysis/immunology ; Patient Acuity ; Prospective Studies ; Proteomics/methods ; }, abstract = {Extremely sensitive food-allergic patients may react to very small amounts of allergenic foods. Precautionary allergen labelling (PAL) warns from possible allergenic contaminations. We evaluated by oral food challenge the reactivity to a brand of PAL-labelled milk- and egg-free biscuits of children with severe milk and egg allergy. We explored the ability of proteomic methods to identify minute amounts of milk/egg allergens in such biscuits. Traces of milk and/or egg allergens in biscuits were measured by two different liquid-chromatography-mass spectrometry methods. The binding of patient's serum with egg/milk proteins was assessed using immunoblotting. None of the patients reacted to biscuits. Egg and milk proteins were undetectable with a limit of detection of 0.6 µg/g for milk and egg (method A), and of 0.1 and 0.3 µg /g for milk and egg, respectively (method B). The immunoblots did not show milk/egg proteins in the studied biscuits. Milk/egg content of the biscuits is far lower than 4 µg of milk or egg protein per gram of product, the minimal doses considered theoretically capable of causing reactions. With high sensitivity, proteomic assessments predict the harmlessness of very small amount of allergens in foods, and can be used to help avoiding unnecessary PAL.}, }
@article {pmid34959740, year = {2021}, author = {Del Chierico, F and Trapani, V and Petito, V and Reddel, S and Pietropaolo, G and Graziani, C and Masi, L and Gasbarrini, A and Putignani, L and Scaldaferri, F and Wolf, FI}, title = {Dietary Magnesium Alleviates Experimental Murine Colitis through Modulation of Gut Microbiota.}, journal = {Nutrients}, volume = {13}, number = {12}, pages = {}, pmid = {34959740}, issn = {2072-6643}, support = {D.1.2017 and D.3.2.2015//Ministry of Education, Universities and Research/ ; }, mesh = {Animals ; Colitis/chemically induced/*microbiology/*therapy ; Dextran Sulfate ; Disease Models, Animal ; Dysbiosis/microbiology/therapy ; Feces/microbiology ; Female ; Gastrointestinal Microbiome/*drug effects ; Magnesium/*pharmacology ; Magnesium Deficiency/microbiology/therapy ; Mice ; Mice, Inbred C57BL ; RNA, Ribosomal, 16S ; }, abstract = {Nutritional deficiencies are common in inflammatory bowel diseases (IBD). In patients, magnesium (Mg) deficiency is associated with disease severity, while in murine models, dietary Mg supplementation contributes to restoring mucosal function. Since Mg availability modulates key bacterial functions, including growth and virulence, we investigated whether the beneficial effects of Mg supplementation during colitis might be mediated by gut microbiota. The effects of dietary Mg modulation were assessed in a murine model of dextran sodium sulfate (DSS)-induced colitis by monitoring magnesemia, weight, and fecal consistency. Gut microbiota were analyzed by 16S-rRNA based profiling on fecal samples. Mg supplementation improved microbiota richness in colitic mice, increased abundance of Bifidobacterium and reduced Enterobacteriaceae. KEEG pathway analysis predicted an increase in biosynthetic metabolism, DNA repair and translation pathways during Mg supplementation and in the presence of colitis, while low Mg conditions favored catabolic processes. Thus, dietary Mg supplementation increases bacteria involved in intestinal health and metabolic homeostasis, and reduces bacteria involved in inflammation and associated with human diseases, such as IBD. These findings suggest that Mg supplementation may be a safe and cost-effective strategy to ameliorate disease symptoms and restore a beneficial intestinal flora in IBD patients.}, }
@article {pmid34959505, year = {2021}, author = {Pane, S and Ristori, MV and Gardini, S and Russo, A and Del Chierico, F and Putignani, L}, title = {Clinical Parasitology and Parasitome Maps as Old and New Tools to Improve Clinical Microbiomics.}, journal = {Pathogens (Basel, Switzerland)}, volume = {10}, number = {12}, pages = {}, pmid = {34959505}, issn = {2076-0817}, support = {Ricerca Corrente 2020 and 2021//Italian Ministry of Health/ ; }, abstract = {A growing body of evidence shows that dysbiotic gut microbiota may correlate with a wide range of disorders; hence, the clinical use of microbiota maps and fecal microbiota transplantation (FMT) can be exploited in the clinic of some infectious diseases. Through direct or indirect ecological and functional competition, FMT may stimulate decolonization of pathogens or opportunistic pathogens, modulating immune response and colonic inflammation, and restoring intestinal homeostasis, which reduces host damage. Herein, we discuss how diagnostic parasitology may contribute to designing clinical metagenomic pipelines and FMT programs, especially in pediatric subjects. The consequences of more specialized diagnostics in the context of gut microbiota communities may improve the clinical parasitology and extend its applications to the prevention and treatment of several communicable and even noncommunicable disorders.}, }
@article {pmid34949230, year = {2021}, author = {Kurki, SN and Kantonen, J and Kaivola, K and Hokkanen, L and Mäyränpää, MI and Puttonen, H and ,  and Martola, J and Pöyhönen, M and Kero, M and Tuimala, J and Carpén, O and Kantele, A and Vapalahti, O and Tiainen, M and Tienari, PJ and Kaila, K and Hästbacka, J and Myllykangas, L}, title = {APOE ε4 associates with increased risk of severe COVID-19, cerebral microhaemorrhages and post-COVID mental fatigue: a Finnish biobank, autopsy and clinical study.}, journal = {Acta neuropathologica communications}, volume = {9}, number = {1}, pages = {199}, pmid = {34949230}, issn = {2051-5960}, support = {341007//Terveyden Tutkimuksen Toimikunta/ ; 336439//Terveyden Tutkimuksen Toimikunta/ ; 335527//Terveyden Tutkimuksen Toimikunta/ ; TYH2021310//Helsingin ja Uudenmaan Sairaanhoitopiiri/ ; }, mesh = {Adult ; Aged ; Apolipoprotein E4/*genetics ; Autopsy ; Biological Specimen Banks ; COVID-19/*complications/diagnosis/epidemiology/*genetics ; Cerebral Hemorrhage/diagnosis/epidemiology/*genetics ; Cohort Studies ; Female ; Finland/epidemiology ; Genetic Association Studies/methods ; Heterozygote ; Humans ; Male ; Mental Fatigue/diagnosis/epidemiology/*genetics ; Microvessels/pathology ; Middle Aged ; *Patient Acuity ; Prospective Studies ; Risk Factors ; Young Adult ; Post-Acute COVID-19 Syndrome ; }, abstract = {Apolipoprotein E ε4 allele (APOE4) has been shown to associate with increased susceptibility to SARS-CoV-2 infection and COVID-19 mortality in some previous genetic studies, but information on the role of APOE4 on the underlying pathology and parallel clinical manifestations is scarce. Here we studied the genetic association between APOE and COVID-19 in Finnish biobank, autopsy and prospective clinical cohort datasets. In line with previous work, our data on 2611 cases showed that APOE4 carriership associates with severe COVID-19 in intensive care patients compared with non-infected population controls after matching for age, sex and cardiovascular disease status. Histopathological examination of brain autopsy material of 21 COVID-19 cases provided evidence that perivascular microhaemorrhages are more prevalent in APOE4 carriers. Finally, our analysis of post-COVID fatigue in a prospective clinical cohort of 156 subjects revealed that APOE4 carriership independently associates with higher mental fatigue compared to non-carriers at six months after initial illness. In conclusion, the present data on Finns suggests that APOE4 is a risk factor for severe COVID-19 and post-COVID mental fatigue and provides the first indication that some of this effect could be mediated via increased cerebrovascular damage. Further studies in larger cohorts and animal models are warranted.}, }
@article {pmid34946243, year = {2021}, author = {Arbune, M and Iancu, AV and Lupasteanu, G and Vasile, MC and Stefanescu, V}, title = {A Challenge of COVID-19: Associated Infective Endocarditis with Streptococcus gordonii in a Young Immunocompetent Patient.}, journal = {Medicina (Kaunas, Lithuania)}, volume = {57}, number = {12}, pages = {}, pmid = {34946243}, issn = {1648-9144}, mesh = {*COVID-19 ; *Endocarditis/diagnosis/drug therapy ; Female ; Humans ; Pandemics ; SARS-CoV-2 ; Streptococcus gordonii ; }, abstract = {The COVID-19 pandemic is a new challenge for the diagnosis and treatment of infective endocarditis (IE). Fever and other unspecific symptoms of coronaviral infection could be misleading or masking its manifestations. We present the case of a young patient admitted for persistent fever, profuse sweating, headache, articular pain, myalgias, and weight loss. She reported regression taste and smell disorders compared to a month earlier when diagnosed with moderate COVID-19 pneumonia. While the RT-PCR SARS-COV-2 test was positive, she was admitted to a COVID-19 ward. Investigations of febrile syndrome revealed two positive blood cultures with Streptococcus gordonii and the presence of vegetations on the aortic valve, supporting a certain diagnosis of IE. After six weeks of antibiotic treatment, the patient had clinical and biologic favorable outcomes. Streptococcus gordonii is a common commensal related to the dental biofilm, although there were no caries in our patient. The influence of COVID-19 infection on the human microbiome by modifying the virulence of some commensal germs may be a risk factor for IE pathogenesis on native valves and requires the vigilance of clinicians for suspicion of this disease.}, }
@article {pmid34943387, year = {2021}, author = {Sainz, T and Pignataro, V and Bonifazi, D and Ravera, S and Mellado, MJ and Pérez-Martínez, A and Escudero, A and Ceci, A and Calvo, C}, title = {Human Microbiome in Children, at the Crossroad of Social Determinants of Health and Personalized Medicine.}, journal = {Children (Basel, Switzerland)}, volume = {8}, number = {12}, pages = {}, pmid = {34943387}, issn = {2227-9067}, support = {777554//European Union- Horizon 2020/ ; }, abstract = {The evolving field of microbiome research offers an excellent opportunity for biomarker identification, understanding drug metabolization disparities, and improving personalized medicine. However, the complexities of host-microbe ecological interactions hinder clinical transferability. Among other factors, the microbiome is deeply influenced by age and social determinants of health, including environmental factors such as diet and lifestyle conditions. In this article, the bidirectionality of social and host-microorganism interactions in health will be discussed. While the field of microbiome-related personalized medicine evolves, it is clear that social determinants of health should be mitigated. Furthermore, microbiome research exemplifies the need for specific pediatric investigation plans to improve children's health.}, }
@article {pmid34942687, year = {2022}, author = {Jeong, S}, title = {Factors influencing development of the infant microbiota: from prenatal period to early infancy.}, journal = {Clinical and experimental pediatrics}, volume = {65}, number = {9}, pages = {439-447}, pmid = {34942687}, issn = {2713-4148}, abstract = {During early life, the gut microbial composition rapidly changes by maternal microbiota composition, delivery mode, infant feeding mode, antibiotic usage, and various environmental factors, such as the presence of pets and siblings. An integrative study on the diet, the microbiota, and genomic activity at the transcriptomic level may give an insight into the role of diet in shaping the human/microbiome relationship. Disruption in the gut microbiota (i.e., gut dysbiosis) has been linked to necrotizing enterocolitis in infancy, as well as some chronic diseases in later, including obesity, diabetes, inflammatory bowel disease, cancer, allergies, and asthma. Therefore, understanding the impact of maternal-to-infant transfer of dysbiotic microbes and then modifying infant early colonization or correcting early-life gut dysbiosis might be a potential strategy to overcome chronic health conditions.}, }
@article {pmid34940122, year = {2021}, author = {Ghannoum, MA and McCormick, TS and Retuerto, M and Bebek, G and Cousineau, S and Hartman, L and Barth, C and Schrom, K}, title = {Evaluation of Microbiome Alterations Following Consumption of BIOHM, a Novel Probiotic.}, journal = {Current issues in molecular biology}, volume = {43}, number = {3}, pages = {2135-2146}, pmid = {34940122}, issn = {1467-3045}, support = {R01 AI145289/AI/NIAID NIH HHS/United States ; AI145289//National Institute of Allergy and Infectious Diseases/ ; }, mesh = {Candida albicans ; Dysbiosis/*microbiology ; Healthy Volunteers ; Humans ; Metagenomics/methods ; Microbial Interactions ; *Microbiota ; Mycobiome ; Probiotics/*administration &amp; dosage ; RNA, Ribosomal, 16S ; }, abstract = {Gastrointestinal microbiome dysbiosis may result in harmful effects on the host, including those caused by inflammatory bowel diseases (IBD). The novel probiotic BIOHM, consisting of Bifidobacterium breve, Saccharomyces boulardii, Lactobacillus acidophilus, L. rhamnosus, and amylase, was developed to rebalance the bacterial-fungal gut microbiome, with the goal of reducing inflammation and maintaining a healthy gut population. To test the effect of BIOHM on human subjects, we enrolled a cohort of 49 volunteers in collaboration with the Fermentation Festival group (Santa Barbara, CA, USA). The profiles of gut bacterial and fungal communities were assessed via stool samples collected at baseline and following 4 weeks of once-a-day BIOHM consumption. Mycobiome analysis following probiotic consumption revealed an increase in Ascomycota levels in enrolled individuals and a reduction in Zygomycota levels (p value < 0.01). No statistically significant difference in Basidiomycota was detected between pre- and post-BIOHM samples and control abundance profiles (p > 0.05). BIOHM consumption led to a significant reduction in the abundance of Candida genus in tested subjects (p value < 0.013), while the abundance of C. albicans also trended lower than before BIOHM use, albeit not reaching statistical significance. A reduction in the abundance of Firmicutes at the phylum level was observed following BIOHM use, which approached levels reported for control individuals reported in the Human Microbiome Project data. The preliminary results from this clinical study suggest that BIOHM is capable of significantly rebalancing the bacteriome and mycobiome in the gut of healthy individuals, suggesting that further trials examining the utility of the BIOHM probiotic in individuals with gastrointestinal symptoms, where dysbiosis is considered a source driving pathogenesis, are warranted.}, }
@article {pmid34935428, year = {2021}, author = {Zhang, RM and Sun, J and Sun, RY and Wang, MG and Cui, CY and Fang, LX and Liao, MN and Lu, XQ and Liu, YX and Liao, XP and Liu, YH}, title = {Source Tracking and Global Distribution of the Tigecycline Non-Susceptible tet(X).}, journal = {Microbiology spectrum}, volume = {9}, number = {3}, pages = {e0116421}, pmid = {34935428}, issn = {2165-0497}, mesh = {Animals ; Anti-Bacterial Agents/*pharmacology ; Bacterial Proteins/*genetics/metabolism ; Bacteroidaceae/drug effects/*genetics/metabolism ; DNA Transposable Elements ; Drug Resistance, Bacterial ; Escherichia coli/drug effects/*genetics/metabolism ; Flavobacteriaceae/drug effects/*genetics/metabolism ; Gene Transfer, Horizontal ; Humans ; Microbial Sensitivity Tests ; Plasmids/genetics/metabolism ; Riemerella/drug effects/*genetics/metabolism ; Tigecycline/*pharmacology ; }, abstract = {The emergence of tet(X) genes has compromised the clinical use of the last-line antibiotic tigecycline. We identified 322 (1.21%) tet(X) positive samples from 12,829 human microbiome samples distributed in four continents (Asia, Europe, North America, and South America) using retrospective data from worldwide. These tet(X) genes were dominated by tet(X2)-like orthologs but we also identified 12 samples carrying novel tet(X) genes, designed tet(X45), tet(X46), and tet(X47), were resistant to tigecycline. The metagenomic analysis indicated these tet(X) genes distributed in anaerobes dominated by Bacteroidaceae (78.89%) of human-gut origin. Two mobile elements ISBf11 and IS4351 were most likely to promote the transmission of these tet(X2)-like orthologs between Bacteroidaceae and Riemerella anatipestifer. tet(X2)-like orthologs was also developed during transmission by mutation to high-level tigecycline resistant genes tet(X45), tet(X46), and tet(X47). Further tracing these tet(X) in single bacterial isolate from public repository indicated tet(X) genes were present as early as 1960s in R. anatipestifer that was the primary tet(X) carrier at early stage (before 2000). The tet(X2) and non-tet(X2) orthologs were primarily distributed in humans and food animals respectively, and non-tet(X2) were dominated by tet(X3) and tet(X4). Genomic comparison indicated these tet(X) genes were likely to be generated during tet(X) transmission between Flavobacteriaceae and E. coli/Acinetobacter spp., and ISCR2 played a key role in the transmission. These results suggest R. anatipestifer was the potential ancestral source of tet(X). In addition, Bacteroidaceae of human-gut origin was an important hidden reservoir and mutational incubator for the mobile tet(X) genes that enabled spread to facultative anaerobes and aerobes. IMPORTANCE The emergence of the tigecycline resistance gene tet(X) has posed a severe threat to public health. However, reports of its origin and distribution in human remain rare. Here, we explore the origin and distribution of tet(X) from large-scale metagenomic data of human-gut origin and public repository. This study revealed the emergency of tet(X) gene in 1960s, which has refreshed a previous standpoint that the earliest presence of tet(X) was in 1980s. The metagenomic analysis from data mining covered the unculturable bacteria, which has overcome the traditional bacteria isolating and purificating technologies, and the analysis indicated that the Bacteroidaceae of human-gut origin was an important hidden reservoir for tet(X) that enabled spread to facultative anaerobes and aerobes. The continuous monitoring of mobile tigecycline resistance determinants from both culturable and unculturable microorganisms is imperative for understanding and tackling the dissemination of tet(X) genes in both the health care and agricultural sectors.}, }
@article {pmid34929293, year = {2022}, author = {Nel Van Zyl, K and Matukane, SR and Hamman, BL and Whitelaw, AC and Newton-Foot, M}, title = {Effect of antibiotics on the human microbiome: a systematic review.}, journal = {International journal of antimicrobial agents}, volume = {59}, number = {2}, pages = {106502}, doi = {10.1016/j.ijantimicag.2021.106502}, pmid = {34929293}, issn = {1872-7913}, mesh = {Anti-Bacterial Agents/adverse effects ; Child ; Dysbiosis/chemically induced ; *Gastrointestinal Microbiome ; Humans ; *Microbiota ; RNA, Ribosomal, 16S/genetics ; }, abstract = {BACKGROUND: Global antibiotic use has been increasing for decades. The gut microbiome, a key contributor to health, can be altered by antibiotics, which have been associated with both short- and long-term effects on the intestinal microbiome. The aim of this study was to summarize the effects of antibiotics on the diversity and composition of the human microbiota at different anatomical sites.<br><br>METHODS: A systematic review was conducted according to PRISMA guidelines. PubMed, Scopus and Web of Science online databases were searched for studies that described the microbiome of any human bodily site pre- and post-antibiotic treatment using 16S rRNA gene sequencing. Increases or decreases in diversity, dissimilarity of microbial communities, and changes in taxonomic composition following antibiotic treatment were recorded as outcome measures.<br><br>RESULTS: The review identified consistent changes in the microbiota following quinolone and metronidazole treatment, and showed that combination treatment may result in longer-term dysbiosis. The importance of longitudinal analysis, and a lack of studies in paediatric populations was highlighted. Heterogeneity in the methodology of included studies could have contributed to the inconsistent findings regarding the effect of most antibiotic classes on the microbiome.<br><br>CONCLUSIONS: It is recommended that studies investigating the effect of antibiotics on the microbiome need to exclude participants exposed to antibiotics within 4 months preceding collection and analysis of baseline samples, and to include longitudinal analysis, particularly in the longer term. Further explorations need to be made into the functional implications of antibiotic-induced dysbiosis in the microbiome.<br><br>PROSPERO (https://www.crd.york.ac.uk/prospero; Registration:CRD42020168991).}, }
@article {pmid34928256, year = {2022}, author = {Verstraelen, H and Vieira-Baptista, P and De Seta, F and Ventolini, G and Lonnee-Hoffmann, R and Lev-Sagie, A}, title = {The Vaginal Microbiome: I. Research Development, Lexicon, Defining "Normal" and the Dynamics Throughout Women's Lives.}, journal = {Journal of lower genital tract disease}, volume = {26}, number = {1}, pages = {73-78}, pmid = {34928256}, issn = {1526-0976}, mesh = {Adolescent ; Bacteria ; Female ; Humans ; Infant, Newborn ; Menopause ; *Microbiota ; Research ; Vagina ; }, abstract = {OBJECTIVE: This series of articles, titled The Vaginal Microbiome, written on behalf of the International Society for the Study of Vulvovaginal Disease, aims to summarize the current findings and understanding of the vaginal bacterial microbiota, mainly regarding areas relevant to clinicians specializing in vulvovaginal disorders.<br><br>MATERIALS AND METHODS: A database search of PubMed was performed, using the search terms "vaginal microbiome" (VMB) with "research," "normal," "neonate," "puberty," "adolescent," "menopause," and "ethnicities," as well as "human microbiome project." Full article texts were reviewed. Reference lists were screened for additional articles.<br><br>RESULTS: In the last 2 decades, many studies applying molecular techniques were performed, intending to characterize the vaginal microbiota. These studies advanced our understanding of how vaginal health is defined. The first article in this series focuses on the advancement of VMB research, technical definitions, the definition of "normal" VMB, and the dynamics of VMB throughout women's lives.<br><br>CONCLUSIONS: Understanding how microorganisms inhabiting the vagina interact with each other and with the host is important for a more complete understanding of vaginal health. The clinical application of microbial community sequencing is in its beginning, and its interpretation regarding practical clinical aspects is yet to be determined.}, }
@article {pmid34917651, year = {2021}, author = {Parolin, C and Zhu, W and Zhu, J}, title = {Editorial: Metabolomics of Human Microbiome Studies: Recent Advances in Methods and Applications.}, journal = {Frontiers in molecular biosciences}, volume = {8}, number = {}, pages = {800337}, pmid = {34917651}, issn = {2296-889X}, }
@article {pmid34917047, year = {2021}, author = {Lin, S and Zhang, H and Wang, X and Lin, T and Chen, Z and Liu, J and Wang, J}, title = {Abundance of Lipopolysaccharide Heptosyltransferase I in Human Gut Microbiome and Its Association With Cardiovascular Disease and Liver Cirrhosis.}, journal = {Frontiers in microbiology}, volume = {12}, number = {}, pages = {756976}, pmid = {34917047}, issn = {1664-302X}, abstract = {Lipopolysaccharide (LPS) is a potent endotoxin on the outer membrane of gram-negative bacteria. Heptosyltransferase I (HpeI) takes part in the synthesis of LPS. In this study, we first collected the protein sequences of HpeI homologs from the human microbiome. The collected HpeI sequences was classified based on sequence similarity, and seven clusters of HpeI were obtained. Among these clusters, proteins from Cluster 3 were abundant in the human mouth, while Clusters 1, 6, and 7 were abundant in the human gut. In addition, proteins from Cluster 1 were mainly from the order of Enterobacterales, while Cluster 6 and 7 were from Burkholderiales. The correlation analysis indicated that the total abundance of HpeIs was increased in patients with cardiovascular disease and liver cirrhosis, and HpeI in Cluster 1 contributed to this increase. These data suggest that HpeI homologs in Cluster 1 can be recognized as biomarkers for cardiovascular disease and liver cirrhosis, and that reducing the bacterial load in Cluster 1 may contribute to disease therapy.}, }
@article {pmid34911583, year = {2021}, author = {Allali, I and Abotsi, RE and Tow, LA and Thabane, L and Zar, HJ and Mulder, NM and Nicol, MP}, title = {Human microbiota research in Africa: a systematic review reveals gaps and priorities for future research.}, journal = {Microbiome}, volume = {9}, number = {1}, pages = {241}, pmid = {34911583}, issn = {2049-2618}, support = {U54 HG009824/HG/NHGRI NIH HHS/United States ; U41 HG006941/HG/NHGRI NIH HHS/United States ; }, mesh = {Humans ; Mass Screening ; *Microbiota ; Public Health ; South Africa ; Uganda ; }, abstract = {BACKGROUND: The role of the human microbiome in health and disease is an emerging and important area of research; however, there is a concern that African populations are under-represented in human microbiome studies. We, therefore, conducted a systematic survey of African human microbiome studies to provide an overview and identify research gaps. Our secondary objectives were: (i) to determine the number of peer-reviewed publications; (ii) to identify the extent to which the researches focused on diseases identified by the World Health Organization [WHO] State of Health in the African Region Report as being the leading causes of morbidity and mortality in 2018; (iii) to describe the extent and pattern of collaborations between researchers in Africa and the rest of the world; and (iv) to identify leadership and funders of the studies.<br><br>METHODOLOGY: We systematically searched Medline via PubMed, Scopus, CINAHL, Academic Search Premier, Africa-Wide Information through EBSCOhost, and Web of Science from inception through to 1st April 2020. We included studies that characterized samples from African populations using next-generation sequencing approaches. Two reviewers independently conducted the literature search, title and abstract, and full-text screening, as well as data extraction.<br><br>RESULTS: We included 168 studies out of 5515 records retrieved. Most studies were published in PLoS One (13%; 22/168), and samples were collected from 33 of the 54 African countries. The country where most studies were conducted was South Africa (27/168), followed by Kenya (23/168) and Uganda (18/168). 26.8% (45/168) focused on diseases of significant public health concern in Africa. Collaboration between scientists from the United States of America and Africa was most common (96/168). The first and/or last authors of 79.8% of studies were not affiliated with institutions in Africa. Major funders were the United States of America National Institutes of Health (45.2%; 76/168), Bill and Melinda Gates Foundation (17.8%; 30/168), and the European Union (11.9%; 20/168).<br><br>CONCLUSIONS: There are significant gaps in microbiome research in Africa, especially those focusing on diseases of public health importance. There is a need for local leadership, capacity building, intra-continental collaboration, and national government investment in microbiome research within Africa. Video Abstract.}, }
@article {pmid34900793, year = {2021}, author = {Mane, S and Dixit, KK and Lathwal, N and Dhotre, D and Kadus, P and Shouche, YS and Bhalerao, S}, title = {Rectal administration of buttermilk processed with medicinal plants alters gut microbiome in obese individuals.}, journal = {Journal of diabetes and metabolic disorders}, volume = {20}, number = {2}, pages = {1415-1427}, pmid = {34900793}, issn = {2251-6581}, abstract = {OBJECTIVE: To evaluate the effect of rectal administration of buttermilk processed with medicinal plants on gut microbial composition and thereby on weight in obese individuals.<br><br>METHODS: With ethics&#xa0;committee approval, 16 obese individuals in the age group 20-50&#xa0;years (BMI &#x2265;30&#xa0;kg/m[2]) were recruited who received a course of 15-enemas over 15-days. Of these, 1st, 8th and 15th enemas were of sesame-oil administered after food, while other enemas were of buttermilk processed with medicinal plants administered before food. Outcome variables viz. anthropometry, body composition, blood glucose, insulin and lipid profile were evaluated on day 0, 16 and 45. Also,&#xa0;microbial composition of buttermilk preparation and faecal samples of patients collected on day 0, 16 and 45 were studied with the help of 16S rRNA gene sequencing.<br><br>RESULTS: The circumferential measures and skinfold-thickness showed a decrease on day 16, which remained lower as compared to baseline till day 45. A gradual decrease in blood-glucose was seen, which was statistically significant on day 45, while insulin levels increased on day 16 and fell to baseline on day 45. There was an overall increase in bacterial diversity on day 16 that settled back to its original composition by day 45.<br><br>CONCLUSION: Our findings suggest that buttermilk administration per rectum is effective for a specific period and may have to be repeated for sustained benefits.<br><br>SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40200-021-00879-z.}, }
@article {pmid34900137, year = {2021}, author = {Narayana, JK and Mac Aogáin, M and Goh, WWB and Xia, K and Tsaneva-Atanasova, K and Chotirmall, SH}, title = {Mathematical-based microbiome analytics for clinical translation.}, journal = {Computational and structural biotechnology journal}, volume = {19}, number = {}, pages = {6272-6281}, pmid = {34900137}, issn = {2001-0370}, abstract = {Traditionally, human microbiology has been strongly built on the laboratory focused culture of microbes isolated from human specimens in patients with acute or chronic infection. These approaches primarily view human disease through the lens of a single species and its relevant clinical setting however such approaches fail to account for the surrounding environment and wide microbial diversity that exists in vivo. Given the emergence of next generation sequencing technologies and advancing bioinformatic pipelines, researchers now have unprecedented capabilities to characterise the human microbiome in terms of its taxonomy, function, antibiotic resistance and even bacteriophages. Despite this, an analysis of microbial communities has largely been restricted to ordination, ecological measures, and discriminant taxa analysis. This is predominantly due to a lack of suitable computational tools to facilitate microbiome analytics. In this review, we first evaluate the key concerns related to the inherent structure of microbiome datasets which include its compositionality and batch effects. We describe the available and emerging analytical techniques including integrative analysis, machine learning, microbial association networks, topological data analysis (TDA) and mathematical modelling. We also present how these methods may translate to clinical settings including tools for implementation. Mathematical based analytics for microbiome analysis represents a promising avenue for clinical translation across a range of acute and chronic disease states.}, }
@article {pmid34896087, year = {2022}, author = {Naspolini, NF and Meyer, A and Moreira, JC and Sun, H and Froes-Asmus, CIR and Dominguez-Bello, MG}, title = {Environmental pollutant exposure associated with altered early-life gut microbiome: Results from a birth cohort study.}, journal = {Environmental research}, volume = {205}, number = {}, pages = {112545}, doi = {10.1016/j.envres.2021.112545}, pmid = {34896087}, issn = {1096-0953}, support = {P30 ES005022/ES/NIEHS NIH HHS/United States ; }, mesh = {Birth Cohort ; Cohort Studies ; *Environmental Pollutants/toxicity ; Feces ; Female ; *Gastrointestinal Microbiome ; Humans ; Infant ; Infant, Newborn ; Pregnancy ; RNA, Ribosomal, 16S/genetics ; }, abstract = {Emerging evidence shows that the gut microbiota interacts with environmental pollutants, but the effect of early exposure on the neonatal microbiome remains unknown. We investigated the association between maternal exposure to environmental pollutants and changes in early-life gut microbiome development. We surveyed 16S rRNA gene on meconium and fecal samples (at 1, 3, and 6 months) from the Brazilian birth cohort, and associated with levels of metals, perfluoroalkyl chemicals (PFAS), and pesticides in maternal and umbilical cord blood. The results indicate that the magnitude of the microbiome changes associated with increasing pollutant exposure was bigger in cesarean-section (CS) born and CS-born-preterm babies, in relation to vaginally (VG) delivered infants. Breastfeeding was associated with a stronger pollutant-associated effect on the infant feces, suggesting that the exposure source could be maternal milk. Differences in microbiome effects associated with maternal or cord blood pollutant concentrations suggest that fetal exposure time - intrauterine or perinatal - may matter. Finally, despite the high developmental microbiota variability, specific microbionts were consistently affected across all pollutants, with taxa clusters found in samples from infants exposed to the highest toxicant exposure. The results evidence that perinatal exposure to environmental pollutants is associated with alterations in gut microbiome development which may have health significance.}, }
@article {pmid34896030, year = {2022}, author = {Maslennikov, R and Ivashkin, V and Ufimtseva, A and Poluektova, E}, title = {Two consecutive attacks of diarrhea in 15 COVID-19 patients: An antibiotic-associated one following the viral one.}, journal = {Revista de gastroenterologia de Mexico (English)}, volume = {87}, number = {1}, pages = {59-62}, pmid = {34896030}, issn = {2255-534X}, mesh = {Anti-Bacterial Agents/adverse effects ; *COVID-19 ; Diarrhea/chemically induced ; Female ; Humans ; Intensive Care Units ; Middle Aged ; SARS-CoV-2 ; }, abstract = {Of the 971 patients admitted to our Clinic with suspected COVID-19, 15 (1.5%) presented with two consecutive attacks of diarrhea. One of those patients (a 47-year-old woman) required admission to the intensive care unit and mechanical ventilation. She died on the 11th day of hospitalization (18th day of illness). The first attack of diarrhea in those patients occurred on the 6th (4th-7th) day of disease and lasted 3 (3-5) days. The second attack of diarrhea developed 11 (8-12) days after the initial onset of diarrhea. Despite the existing trend, the difference in the duration of the diarrhea and the maximum number of bowel movements per day between the first and second attacks was not statistically significant (p = 0.130; p = 0.328). There was no significant difference between the patients with a double attack of diarrhea and those with no diarrhea, regarding the results of the complete blood count, biochemical blood tests, and inflammation biomarkers.}, }
@article {pmid34888397, year = {2021}, author = {Presti, RM and Yeh, E and Williams, B and Landay, A and Jacobson, JM and Wilson, C and Fichtenbaum, CJ and Utay, NS and Dube, MP and Klingman, KL and Estes, JD and Flynn, JK and Loftin, A and Brenchley, JM and Andrade, A and Kitch, DW and Overton, ET}, title = {A Randomized, Placebo-Controlled Trial Assessing the Effect of VISBIOME ES Probiotic in People With HIV on Antiretroviral Therapy.}, journal = {Open forum infectious diseases}, volume = {8}, number = {12}, pages = {ofab550}, pmid = {34888397}, issn = {2328-8957}, support = {UM1 AI069494/AI/NIAID NIH HHS/United States ; UM1 AI069501/AI/NIAID NIH HHS/United States ; UM1 AI069432/AI/NIAID NIH HHS/United States ; UM1 AI069439/AI/NIAID NIH HHS/United States ; UM1 AI068634/AI/NIAID NIH HHS/United States ; UM1 AI069481/AI/NIAID NIH HHS/United States ; U01 AI069432/AI/NIAID NIH HHS/United States ; UM1 AI106701/AI/NIAID NIH HHS/United States ; UL1 TR002243/TR/NCATS NIH HHS/United States ; UM1 AI069419/AI/NIAID NIH HHS/United States ; UL1 TR001881/TR/NCATS NIH HHS/United States ; UM1 AI068636/AI/NIAID NIH HHS/United States ; UM1 AI069452/AI/NIAID NIH HHS/United States ; UM1 AI069496/AI/NIAID NIH HHS/United States ; }, abstract = {BACKGROUND: A5350, a phase II, randomized, double-blind study, evaluated the safety and tolerability of the probiotic Visbiome Extra Strength (ES) over 24 weeks and measured effects on inflammation and intestinal barrier function.<br><br>METHODS: The primary outcome was change in soluble CD14 (sCD14) levels; secondary outcomes included safety and tolerability, markers of inflammation and cellular activation, and microbiome. In a substudy, gut permeability was assessed by paired colonic biopsies measuring the area of lamina propria occupied by CD4+ cells, interleukin (IL)-17+ cells, and myeloperoxidase (MPO). Changes between arms were compared with the 2-sample t test with equal variance or the Wilcoxon rank-sum test. For safety, the highest graded adverse events (AEs) were compared between arms using the Fisher exact test.<br><br>RESULTS: Overall, 93 participants enrolled: 86% male, median age 51 years, median CD4 count 712 cells/mm3. Visbiome ES was safe and well tolerated. There was no difference in mean change in sCD14 from baseline to week 25/26 between placebo (mean change, 92.3 &#xb5;g/L; 95% CI, -48.5 to 233 &#xb5;g/L) and Visbiome ES (mean change, 41.0 &#xb5;g/L; 95% CI, -94.1 to 176.2 &#xb5;g/L; P=.60). Similarly, no statistically significant differences between arms in inflammatory marker changes were identified. In substudy participants, no statistical differences between arms for change in cellular marker expression or gut permeability were observed (P>.05 for all). The microbiome demonstrated increased probiotic species and a significant decrease in Gammaproteobacteria (P=.044) in the Visbiome ES arm.<br><br>CONCLUSIONS: Visbiome ES was safe and altered the microbiome but demonstrated no effect on systemic inflammatory markers, pathology, or gut permeability in antiretroviral therapy-treated people with HIV.}, }
@article {pmid34886156, year = {2021}, author = {Fischer, JAJ and Karakochuk, CD}, title = {Feasibility of an At-Home Adult Stool Specimen Collection Method in Rural Cambodia.}, journal = {International journal of environmental research and public health}, volume = {18}, number = {23}, pages = {}, pmid = {34886156}, issn = {1660-4601}, support = {ID400771//CIHR/Canada ; }, mesh = {Adult ; Cambodia ; Feasibility Studies ; Feces ; Female ; Humans ; *Microbiota ; Specimen Handling ; }, abstract = {The human microbiome has received significant attention over the past decade regarding its potential impact on health. Epidemiological and intervention studies often rely on at-home stool collection methods designed for high-resource settings, such as access to an improved toilet with a modern toilet seat. However, this is not always appropriate or applicable to low-resource settings. Therefore, the design of a user-friendly stool collection kit for low-resource rural settings is needed. We describe the development, assembly, and user experience of a simple and low-cost at-home stool collection kit for women living in rural Cambodia as part of a randomized controlled trial in 2020. Participants were provided with the stool collection kit and detailed verbal instruction. Enrolled women (n = 480) provided two stool specimens (at the start of the trial and after 12 weeks) at their home and brought them to the health centre that morning in a sterile collection container. User specimen collection compliance was high, with 90% (n = 434) of women providing a stool specimen at the end of the trial (after 12 weeks). This feasible and straightforward method has strong potential for similar or adapted use among adults residing in other rural or low-resource contexts.}, }
@article {pmid34885015, year = {2021}, author = {Gugnacki, P and Sierko, E}, title = {Is There an Interplay between Oral Microbiome, Head and Neck Carcinoma and Radiation-Induced Oral Mucositis?.}, journal = {Cancers}, volume = {13}, number = {23}, pages = {}, pmid = {34885015}, issn = {2072-6694}, abstract = {Head and neck carcinoma is one of the most common human malignancy types and it ranks as the sixth most common cancer worldwide. Nowadays, a great potential of microbiome research is observed in oncology-investigating the effect of oral microbiome in oncogenesis, occurrence of treatment side effects and response to anticancer therapies. The microbiome is a unique collection of microorganisms and their genetic material, interactions and products residing within the mucous membranes. The aim of this paper is to summarize current research on the oral microbiome and its impact on the development of head and neck cancer and radiation-induced oral mucositis. Human microbiome might determine an oncogenic effect by, among other things, inducing chronic inflammatory response, instigating cellular antiapoptotic signals, modulation of anticancer immunity or influencing xenobiotic metabolism. Influence of oral microbiome on radiation-induced oral mucositis is expressed by the production of additional inflammatory cytokines and facilitates progression and aggravation of mucositis. Exacerbated acute radiation reaction and bacterial superinfections lead to the deterioration of the patient's condition and worsening of the quality of life. Simultaneously, positive effects of probiotics on the course of radiation-induced oral mucositis have been observed. Understanding the impact on the emerging acute radiation reaction on the composition of the microflora can be helpful in developing a multifactorial model to forecast the course of radiation-induced oral mucositis. Investigating these processes will allow us to create optimized and personalized preventive measures and treatment aimed at their formation mechanism. Further studies are needed to better establish the structure of the oral microbiome as well as the dynamics of its changes before and after therapy. It will help to expand the understanding of the biological function of commensal and pathogenic oral microbiota in HNC carcinogenesis and the development of radiation-induced oral mucositis.}, }
@article {pmid34884776, year = {2021}, author = {Sammallahti, H and Kokkola, A and Rezasoltani, S and Ghanbari, R and Asadzadeh Aghdaei, H and Knuutila, S and Puolakkainen, P and Sarhadi, VK}, title = {Microbiota Alterations and Their Association with Oncogenomic Changes in Pancreatic Cancer Patients.}, journal = {International journal of molecular sciences}, volume = {22}, number = {23}, pages = {}, pmid = {34884776}, issn = {1422-0067}, mesh = {Carcinoma, Pancreatic Ductal/*microbiology/pathology/therapy ; Cell Transformation, Neoplastic/pathology ; Dysbiosis/*microbiology ; Gastrointestinal Microbiome/*physiology ; Humans ; Mouth/microbiology ; Pancreas/*microbiology/pathology ; Pancreatic Neoplasms/*microbiology/pathology/therapy ; }, abstract = {Pancreatic cancer (PC) is an aggressive disease with a high mortality and poor prognosis. The human microbiome is a key factor in many malignancies, having the ability to alter host metabolism and immune responses and participate in tumorigenesis. Gut microbes have an influence on physiological functions of the healthy pancreas and are themselves controlled by pancreatic secretions. An altered oral microbiota may colonize the pancreas and cause local inflammation by the action of its metabolites, which may lead to carcinogenesis. The mechanisms behind dysbiosis and PC development are not completely clear. Herein, we review the complex interactions between PC tumorigenesis and the microbiota, and especially the question, whether and how an altered microbiota induces oncogenomic changes, or vice versa, whether cancer mutations have an impact on microbiota composition. In addition, the role of the microbiota in drug efficacy in PC chemo- and immunotherapies is discussed. Possible future scenarios are the intentional manipulation of the gut microbiota in combination with therapy or the utilization of microbial profiles for the noninvasive screening and monitoring of PC.}, }
@article {pmid34884466, year = {2021}, author = {Yu, D and Meng, X and de Vos, WM and Wu, H and Fang, X and Maiti, AK}, title = {Implications of Gut Microbiota in Complex Human Diseases.}, journal = {International journal of molecular sciences}, volume = {22}, number = {23}, pages = {}, pmid = {34884466}, issn = {1422-0067}, support = {YDZJ202101ZYTS080//Jilin Province Science and Technology Department/ ; }, mesh = {Anti-Bacterial Agents/adverse effects ; Diet/*adverse effects ; Dysbiosis/etiology/*therapy ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/*drug effects ; Humans ; Prebiotics/adverse effects ; Probiotics/adverse effects ; }, abstract = {Humans, throughout the life cycle, from birth to death, are accompanied by the presence of gut microbes. Environmental factors, lifestyle, age and other factors can affect the balance of intestinal microbiota and their impact on human health. A large amount of data show that dietary, prebiotics, antibiotics can regulate various diseases through gut microbes. In this review, we focus on the role of gut microbes in the development of metabolic, gastrointestinal, neurological, immune diseases and, cancer. We also discuss the interaction between gut microbes and the host with respect to their beneficial and harmful effects, including their metabolites, microbial enzymes, small molecules and inflammatory molecules. More specifically, we evaluate the potential ability of gut microbes to cure diseases through Fecal Microbial Transplantation (FMT), which is expected to become a new type of clinical strategy for the treatment of various diseases.}, }
@article {pmid34884327, year = {2021}, author = {Daniluk, J and Daniluk, U and Rogalski, P and Dabrowski, A and Swidnicka-Siergiejko, A}, title = {Microbiome-Friend or Foe of Pancreatic Cancer?.}, journal = {Journal of clinical medicine}, volume = {10}, number = {23}, pages = {}, pmid = {34884327}, issn = {2077-0383}, support = {2017/27/B/NZ5/02904//National Science Center/ ; }, abstract = {Pancreatic ductal adenocarcinoma is one of the deadliest human neoplasms. Despite the development of new surgical and adjuvant therapies, the prognosis remains very poor, with the overall survival rate not exceeding 9%. There is now increasing evidence that the human microbiome, which is involved in many physiological functions, including the regulation of metabolic processes and the modulation of the immune system, is possibly linked to pancreatic oncogenesis. However, the exact mechanisms of action are poorly understood. Our review summarizes the current understanding of how the microbiome affects pancreatic cancer development and progression. We discuss potential pathways of microbe translocation to the pancreas, as well as the mechanism of their action. We describe the role of the microbiome as a potential marker of pancreatic cancer diagnosis, progression, and survival. Finally, we discuss the possibilities of modifying the microbiome to improve treatment effectiveness for this deadly disease.}, }
@article {pmid34880965, year = {2022}, author = {Barb, JJ and Maki, KA and Kazmi, N and Meeks, BK and Krumlauf, M and Tuason, RT and Brooks, AT and Ames, NJ and Goldman, D and Wallen, GR}, title = {The oral microbiome in alcohol use disorder: a longitudinal analysis during inpatient treatment.}, journal = {Journal of oral microbiology}, volume = {14}, number = {1}, pages = {2004790}, pmid = {34880965}, issn = {2000-2297}, abstract = {BACKGROUND: Alcohol use disorder (AUD)-induced disruption of oral microbiota can lead to poor oral health; there have been no studies published examining the longitudinal effects of alcohol use cessation on the oral microbiome.<br><br>AIM: To investigate the oral microbiome during alcohol cessation during inpatient treatment for AUD.<br><br>METHODS: Up to 10 oral tongue brushings were collected from 22 AUD patients during inpatient treatment at the National Institutes of Health. Alcohol use history, smoking, and periodontal disease status were measured. Oral microbiome samples were sequenced using 16S rRNA gene sequencing.<br><br>RESULTS: Alpha diversity decreased linearly during treatment across the entire cohort (P =&#xa0;0.002). Alcohol preference was associated with changes in both alpha and beta diversity measures. Characteristic tongue dorsum genera from the Human Microbiome Project such as Streptococcus, Prevotella, Veillonella and Haemophilus were highly correlated in AUD. Oral health-associated genera that changed longitudinally during abstinence included Actinomyces, Capnocytophaga, Fusobacterium, Neisseria and Prevotella.<br><br>CONCLUSION: The oral microbiome in AUD is affected by alcohol preference. Patients with AUD often have poor oral health but abstinence and attention to oral care improve dysbiosis, decreasing microbiome diversity and periodontal disease-associated genera while improving acute oral health.}, }
@article {pmid34879270, year = {2021}, author = {Daisley, BA and Koenig, D and Engelbrecht, K and Doney, L and Hards, K and Al, KF and Reid, G and Burton, JP}, title = {Emerging connections between gut microbiome bioenergetics and chronic metabolic diseases.}, journal = {Cell reports}, volume = {37}, number = {10}, pages = {110087}, doi = {10.1016/j.celrep.2021.110087}, pmid = {34879270}, issn = {2211-1247}, mesh = {Animals ; Bacteria/growth &amp; development/*metabolism ; Chronic Disease ; Dysbiosis ; *Energy Metabolism ; Fatty Acids, Volatile/*metabolism ; *Gastrointestinal Microbiome ; Host-Pathogen Interactions ; Humans ; Metabolic Diseases/metabolism/*microbiology ; Symbiosis ; }, abstract = {The conventional viewpoint of single-celled microbial metabolism fails to adequately depict energy flow at the systems level in host-adapted microbial communities. Emerging paradigms instead support that distinct microbiomes develop interconnected and interdependent electron transport chains that rely on cooperative production and sharing of bioenergetic machinery (i.e., directly involved in generating ATP) in the extracellular space. These communal resources represent an important subset of the microbial metabolome, designated here as the "pantryome" (i.e., pantry or external storage compartment), that critically supports microbiome function and can exert multifunctional effects on host physiology. We review these interactions as they relate to human health by detailing the genomic-based sharing potential of gut-derived bacterial and archaeal reference strains. Aromatic amino acids, metabolic cofactors (B vitamins), menaquinones (vitamin K2), hemes, and short-chain fatty acids (with specific emphasis on acetate as a central regulator of symbiosis) are discussed in depth regarding their role in microbiome-related metabolic diseases.}, }
@article {pmid34867436, year = {2021}, author = {Rao, B and Ren, T and Wang, X and Wang, H and Zou, Y and Sun, Y and Liu, S and Ren, Z and Yu, Z}, title = {Dysbiosis in the Human Microbiome of Cholangiocarcinoma.}, journal = {Frontiers in physiology}, volume = {12}, number = {}, pages = {715536}, pmid = {34867436}, issn = {1664-042X}, abstract = {Cholangiocarcinoma (CCA) is the most common malignant tumor of the biliary system with a very poor prognosis. The human microbiome, which is the sum of the genetic information of human microorganisms, plays an important role in regulating the digestion, absorption, immune response, and metabolism of the host. Increasing evidence indicates a close relationship between CCA and the human microbiome. Specific alterations occur in the human microbiome of patients with CCA. Therefore, in this review, we aimed to summarize the recent evidence on dysbiosis in the human microbiome of CCA. Then, we generalized the effect of Helicobacter pylori on CCA. Additionally, the potential mechanism of human microbial dysbiosis promoted the progress of CCA, and its precancerous disease was also explored. Furthermore, the possibility of the human microbiome as a diagnostic and therapeutic target of CCA was discussed.}, }
@article {pmid34866471, year = {2022}, author = {Chen, B and Xu, W}, title = {Functional response regression model on correlated longitudinal microbiome sequencing data.}, journal = {Statistical methods in medical research}, volume = {31}, number = {2}, pages = {361-371}, pmid = {34866471}, issn = {1477-0334}, mesh = {*Gastrointestinal Microbiome/genetics ; Humans ; Least-Squares Analysis ; *Microbiota/genetics ; Research Design ; }, abstract = {Functional regression has been widely used on longitudinal data, but it is not clear how to apply functional regression to microbiome sequencing data. We propose a novel functional response regression model analyzing correlated longitudinal microbiome sequencing data, which extends the classic functional response regression model only working for independent functional responses. We derive the theory of generalized least squares estimators for predictors' effects when functional responses are correlated, and develop a data transformation technique to solve the computational challenge for analyzing correlated functional response data using existing functional regression method. We show by extensive simulations that our proposed method provides unbiased estimations for predictors' effect, and our model has accurate type I error and power performance for correlated functional response data, compared with classic functional response regression model. Finally we implement our method to a real infant gut microbiome study to evaluate the relationship of clinical factors to predominant taxa along time.}, }
@article {pmid34857814, year = {2021}, author = {Korpela, K and Kallio, S and Salonen, A and Hero, M and Kukkonen, AK and Miettinen, PJ and Savilahti, E and Kohva, E and Kariola, L and Suutela, M and Tarkkanen, A and de Vos, WM and Raivio, T and Kuitunen, M}, title = {Gut microbiota develop towards an adult profile in a sex-specific manner during puberty.}, journal = {Scientific reports}, volume = {11}, number = {1}, pages = {23297}, pmid = {34857814}, issn = {2045-2322}, mesh = {Adolescent ; Clostridiaceae ; Cohort Studies ; Estrogens/metabolism ; Feces/microbiology ; Female ; Finland ; Gastrointestinal Microbiome/*physiology ; Gastrointestinal Tract/*microbiology ; Humans ; Male ; Puberty/*physiology ; Ruminococcus ; *Sex Characteristics ; Surveys and Questionnaires ; }, abstract = {Accumulating evidence indicates that gut microbiota may regulate sex-hormone levels in the host, with effects on reproductive health. Very little is known about the development of intestinal microbiota during puberty in humans. To assess the connection between pubertal timing and fecal microbiota, and to assess how fecal microbiota develop during puberty in comparison with adult microbiota, we utilized a Finnish allergy-prevention-trial cohort (Flora). Data collected at 13-year follow-up were compared with adult data from a different Finnish cohort. Among the 13-year-old participants we collected questionnaire information, growth data from school-health-system records and fecal samples from 148 participants. Reference adult fecal samples were received from the Health and Early Life Microbiota (HELMi) cohort (n = 840). Fecal microbiota were analyzed using 16S rRNA gene amplicon sequencing; the data were correlated with pubertal timing and compared with data on adult microbiota. Probiotic intervention in the allergy-prevention-trial cohort was considered as a confounding factor only. The main outcome was composition of the microbiota in relation to pubertal timing (time to/from peak growth velocity) in both sexes separately, and similarity to adult microbiota. In girls, fecal microbiota became more adult-like with pubertal progression (p = 0.009). No such development was observed in boys (p = 0.9). Both sexes showed a trend towards increasing relative abundance of estrogen-metabolizing Clostridia and decreasing Bacteroidia with pubertal development, but this was statistically significant in girls only (p = 0.03). In girls, pubertal timing was associated positively with exposure to cephalosporins prior to the age of 10. Our data support the hypothesis that gut microbiota, particularly members of Ruminococcaceae, may affect pubertal timing, possibly via regulating host sex-hormone levels.Trial registration The registration number for the allergy-prevention-trial cohort: ClinicalTrials.gov, NCT00298337, registered 1 March 2006-Retrospectively registered, https://clinicaltrials.gov/show/NCT00298337 . The adult-comparison cohort (HELMi) is NCT03996304.}, }
@article {pmid34856363, year = {2022}, author = {Morikawa, A and Kawabata, A and Shirahige, K and Akiyama, T and Okamoto, A and Sutani, T}, title = {Altered cervicovaginal microbiota in premenopausal ovarian cancer patients.}, journal = {Gene}, volume = {811}, number = {}, pages = {146083}, doi = {10.1016/j.gene.2021.146083}, pmid = {34856363}, issn = {1879-0038}, mesh = {Adult ; Aged ; Aged, 80 and over ; Bacterial Typing Techniques/methods ; Biomarkers ; Carcinoma, Ovarian Epithelial/*microbiology ; Case-Control Studies ; Cervix Uteri/*microbiology ; DNA, Bacterial ; Female ; Humans ; Japan ; Lactobacillus/classification/genetics ; Metagenome ; *Microbiota ; Middle Aged ; Ovarian Neoplasms/*microbiology ; Postmenopause ; Premenopause ; RNA, Ribosomal, 16S ; Vagina/*microbiology ; Young Adult ; }, abstract = {Nearly three hundred thousand female patients are diagnosed with ovarian cancer in the world annually, and this number shows an increasing trend. However, characteristic symptoms caused by ovarian cancer are so few that early diagnosis remains challenging, and an effective screening method has not yet been established. Here, we conducted a case-control study in Japan to analyze the association between cervicovaginal microbiome and ovarian cancer, using 16S rRNA amplicon sequencing. Analysis of DNA extracted from cervical smear samples revealed Lactobacillus-dominant and Lactobacillus-deficient, highly-diversified bacterial communities in premenopausal and postmenopausal healthy controls, respectively, as reported for vaginal microbiota previously. We found that cervicovaginal microbiota in ovarian cancer patients, regardless of their menopausal status, were frequently a diversified community and similar to those in healthy subjects at postmenopausal ages. The diverse microbiota was associated with the major histotypes of epithelial ovarian cancer, including serous ovarian cancer and ovarian clear cell cancer. The present study implies the potential of a cervicovaginal microbiome biomarker in screening ovarian cancer in premenopausal women.}, }
@article {pmid34853760, year = {2021}, author = {Mamgain, G and Patra, P and Naithani, M and Nath, UK}, title = {The Role of Microbiota in the Development of Cancer Tumour Cells and Lymphoma of B and T Cells.}, journal = {Cureus}, volume = {13}, number = {10}, pages = {e19047}, pmid = {34853760}, issn = {2168-8184}, abstract = {Human body harbours enormous numbers of microbial organisms, including bacteria, viruses, and fungi which have a momentous role in well-being and illness in humans. Immune system shelters us from pathogenic bacteria, microorganisms found in human tissues have many benefits related to the functional movement of the host by regulating important procedures such as immunity, signalling, and breakdown. Lymphocytes assume a significant part in the reaction to bacterial colonization, primarily by prompting a safe reaction to obstruction or initiation. Most immunologically occupant cells have a place with the mucosal invulnerable framework and are continually motioned by dendritic cells or other Antigen introducing cells that gather intestinal samples. Thus, Microbiome is a key contributor to developing lymphoma and specific alterations to microbiome composition could attenuate the risk. There is an indication that microbial morphology can affect and control humanoids. The difference in the composition of these microorganisms is associated with tumour development. With the increased knowledge of the connection among the human microbiome and carcinogenesis, the use of these findings to prevent, predict or diagnose of lymphomas has attracted a great attention. In this article, we explored current knowledge of various microbial ecosystems, their connection with carcinogens and the potential for useful microorganisms to control and prevent B and T cell lymphoma.}, }
@article {pmid34851166, year = {2021}, author = {Piscotta, FJ and Hoffmann, HH and Choi, YJ and Small, GI and Ashbrook, AW and Koirala, B and Campbell, EA and Darst, SA and Rice, CM and Brady, SF}, title = {Metabolites with SARS-CoV-2 Inhibitory Activity Identified from Human Microbiome Commensals.}, journal = {mSphere}, volume = {6}, number = {6}, pages = {e0071121}, pmid = {34851166}, issn = {2379-5042}, support = {T32 GM066699/GM/NIGMS NIH HHS/United States ; R01 GM114450/GM/NIGMS NIH HHS/United States ; R35 GM118130/GM/NIGMS NIH HHS/United States ; R01 AT009562/AT/NCCIH NIH HHS/United States ; R01 AI161278/AI/NIAID NIH HHS/United States ; }, mesh = {Antiviral Agents/*pharmacology ; Bacteria/chemistry/classification/growth &amp; development/*metabolism ; Biological Assay ; Cell Line, Tumor ; Culture Media/*chemistry/pharmacology ; Humans ; *Metabolic Networks and Pathways ; Microbiota/*physiology ; Molecular Docking Simulation ; Protease Inhibitors/pharmacology ; Protein Binding ; SARS-CoV-2/*drug effects ; Symbiosis/*physiology ; }, abstract = {The COVID-19 pandemic has highlighted the need to identify additional antiviral small molecules to complement existing therapies. Although increasing evidence suggests that metabolites produced by the human microbiome have diverse biological activities, their antiviral properties remain poorly explored. Using a cell-based SARS-CoV-2 infection assay, we screened culture broth extracts from a collection of phylogenetically diverse human-associated bacteria for the production of small molecules with antiviral activity. Bioassay-guided fractionation uncovered three bacterial metabolites capable of inhibiting SARS-CoV-2 infection. This included the nucleoside analogue N6-(Δ[2]-isopentenyl)adenosine, the 5-hydroxytryptamine receptor agonist tryptamine, and the pyrazine 2,5-bis(3-indolylmethyl)pyrazine. The most potent of these, N6-(Δ[2]-isopentenyl)adenosine, had a 50% inhibitory concentration (IC50) of 2 μM. These natural antiviral compounds exhibit structural and functional similarities to synthetic drugs that have been clinically examined for use against COVID-19. Our discovery of structurally diverse metabolites with anti-SARS-CoV-2 activity from screening a small fraction of the bacteria reported to be associated with the human microbiome suggests that continued exploration of phylogenetically diverse human-associated bacteria is likely to uncover additional small molecules that inhibit SARS-CoV-2 as well as other viral infections. IMPORTANCE The continued prevalence of COVID-19 and the emergence of new variants has once again put the spotlight on the need for the identification of SARS-CoV-2 antivirals. The human microbiome produces an array of small molecules with bioactivities (e.g., host receptor ligands), but its ability to produce antiviral small molecules is relatively underexplored. Here, using a cell-based screening platform, we describe the isolation of three microbiome-derived metabolites that are able to prevent SARS-CoV-2 infection in vitro. These molecules display structural similarities to synthetic drugs that have been explored for the treatment of COVID-19, and these results suggest that the microbiome may be a fruitful source of the discovery of small molecules with antiviral activities.}, }
@article {pmid34850062, year = {2022}, author = {DiMaio, D and Emu, B and Goodman, AL and Mothes, W and Justice, A}, title = {Cancer Microbiology.}, journal = {Journal of the National Cancer Institute}, volume = {114}, number = {5}, pages = {651-663}, pmid = {34850062}, issn = {1460-2105}, support = {P30CA016359/NH/NIH HHS/United States ; U10 AA013566/AA/NIAAA NIH HHS/United States ; R01 AI150897/AI/NIAID NIH HHS/United States ; P50 CA196530/CA/NCI NIH HHS/United States ; R35 CA242462/CA/NCI NIH HHS/United States ; R01 CA206465/NH/NIH HHS/United States ; }, mesh = {Anti-Bacterial Agents ; Carcinogens ; Delivery of Health Care ; Humans ; *Microbiota ; *Neoplasms/prevention &amp; control ; }, abstract = {Microbes play important roles in cancer from direct carcinogenic effects to their use in treatment. Cancers caused by microorganisms account for approximately 15% of cancers, primarily in low- and middle-income countries. Unique features of infectious carcinogens include their transmissibility, mutability, and specific immune interactions, which provide challenges and opportunities for cancer prevention and treatment. For these agents, infection control through exposure reduction, antivirals, antibiotics, and vaccines is cancer control. In addition, developing evidence suggests that microorganisms including the human microbiome can indirectly modulate cancer formation and influence the effectiveness and toxicity of cancer treatments. Finally, microorganisms themselves can be used to prevent or treat cancer. The convergence of these factors signals the emergence of a new field, cancer microbiology. Recognition of cancer microbiology will spur research, stimulate cross-disciplinary training, inform drug development, and improve public health.}, }
@article {pmid34841785, year = {2021}, author = {Liu, H and Xu, X and Ling, K and Zou, X}, title = {[Vaginal microbiome: community characteristics and disease intervention].}, journal = {Sheng wu gong cheng xue bao = Chinese journal of biotechnology}, volume = {37}, number = {11}, pages = {3801-3811}, doi = {10.13345/j.cjb.210204}, pmid = {34841785}, issn = {1872-2075}, mesh = {Female ; Humans ; *Microbiota ; *Probiotics ; Vagina ; }, abstract = {The application of high-throughput sequencing technologies has greatly enhanced our understanding to the human microbiome. The causal relations between human microbiome and diseases have become a critical issue to elucidate disease development and develop precision medicine. Recently, the study about vaginal microbiome (the microbial flora that inhabits the female vagina) has received wide interests. It has been shown that dysbiosis of vaginal microbiome was closely related to the development of genital tract diseases. This article summarizes the interaction between vaginal microbiome and disease and the treatment for the dysbiosis of vaginal microbiome. The culturomics of virginal microbiome, engineered probiotics and synthetic microbiome were also proposed.}, }
@article {pmid34841779, year = {2021}, author = {Yin, Y and Yu, R and Chen, H}, title = {[Shotgun metagenome sequencing of Chinese gut microbiota: a review].}, journal = {Sheng wu gong cheng xue bao = Chinese journal of biotechnology}, volume = {37}, number = {11}, pages = {3717-3733}, doi = {10.13345/j.cjb.210556}, pmid = {34841779}, issn = {1872-2075}, mesh = {China ; *Gastrointestinal Microbiome/genetics ; Humans ; Metagenome ; *Microbiota ; RNA, Ribosomal, 16S/genetics ; United States ; }, abstract = {The research on the relationship between gut microbiota and human health continues to be a hot topic in the field of life science. Culture independent 16S rRNA gene high-throughput sequencing is the current main research method. However, with the reduction of sequencing cost and the maturity of data analysis methods, shotgun metagenome sequencing is gradually becoming an important method for the study of gut microbiome due to its advantages of obtaining more information. With the support from the human microbiome project, 30 805 metagenome samples were sequenced in the United States. By searching NCBI PubMed and SRA databases, it was found that 72 studies collecting about 10 000 Chinese intestinal samples were used for metagenome sequencing. To date, only 56 studies were published, including 16 related to metabolic diseases, 16 related to infectious and immune diseases, and 12 related to cardiovascular and cerebrovascular diseases. The samples were mainly collected in Beijing, Guangzhou, Shanghai and other cosmopolitan cities, where great differences exist in sequencing platforms and methods. The outcome of most studies are based on correlation analysis, which has little practical value in guiding the diagnosis and treatment of clinical diseases. Standardizing sampling methods, sequencing platform and data analysis process, and carrying out multi center parallel research will contribute to data integration and comparative analysis. Moreover, insights into the functional verification and molecular mechanism by using the combination of transcriptomics, proteomics and culturomics will enable the gut microbiota research to better serve the clinical diagnosis and treatment.}, }
@article {pmid34841778, year = {2021}, author = {Wang, J and Wang, J and Deng, Z}, title = {[Preface for special issue on microbiome and human health].}, journal = {Sheng wu gong cheng xue bao = Chinese journal of biotechnology}, volume = {37}, number = {11}, pages = {3711-3716}, doi = {10.13345/j.cjb.210789}, pmid = {34841778}, issn = {1872-2075}, mesh = {China ; Humans ; Intestines ; Lung ; *Microbiota ; *Neoplasms ; }, abstract = {Human microbiome is comprised of symbiotic microorganisms in the human body, whose dynamic balance is closely related to human health, and is recognized as important "organs" that can regulate immunity, metabolism and other aspects in human body, and is associated with functions of many organs including lung, intestine, vagina and brain, becoming a potential target for the treatment of cancer, coronary heart disease, neurological diseases and other difficult diseases. In recent years, with the rapid development of microbiome sequencing and analysis technology, it has become an international focus and forefront to discover the relationship between human microorganisms and many diseases, as well as target for new treatment methods. Thus, we organized this special issue and publish reviews on study methodology, human disease and microbiome as well as therapeutic strategies, and provide important information to advance microbiome research in China.}, }
@article {pmid34839034, year = {2021}, author = {Sahni, V}, title = {The oral microbiome and vaccine efficacy.}, journal = {Medical hypotheses}, volume = {158}, number = {}, pages = {110732}, doi = {10.1016/j.mehy.2021.110732}, pmid = {34839034}, issn = {1532-2777}, abstract = {The immune response elicited by vaccines is crucial in determining their eventual efficacy. The human microbiome, in particular, that of the gut has been demonstrated to influence the immunogenicity of vaccines delivered by both the oral and non-oral routes. There is a significant overlap between the microflora of the mouth and that recovered from the gut, with certain periodontopathogens playing key roles in influencing the gut microflora. The present paper hypothesized that the oral microflora may play a role in the eventual immunogenicity and efficacy of vaccines.}, }
@article {pmid34834977, year = {2021}, author = {Happonen, LJ and Pajunen, MI and Jun, JW and Skurnik, M}, title = {BtuB-Dependent Infection of the T5-like Yersinia Phage ϕR2-01.}, journal = {Viruses}, volume = {13}, number = {11}, pages = {}, pmid = {34834977}, issn = {1999-4915}, mesh = {Bacterial Outer Membrane Proteins/*metabolism ; Bacterial Proteins/*metabolism ; Bacteriophages/classification/genetics/isolation &amp; purification/physiology ; Genome, Viral ; Membrane Transport Proteins/*metabolism ; Proteomics ; Siphoviridae/classification/genetics/isolation &amp; purification/*physiology ; Yersinia/genetics/*virology ; Yersinia enterocolitica/virology ; }, abstract = {Yersinia enterocolitica is a food-borne Gram-negative pathogen responsible for several gastrointestinal disorders. Host-specific lytic bacteriophages have been increasingly used recently as an alternative or complementary treatment to combat bacterial infections, especially when antibiotics fail. Here, we describe the proteogenomic characterization and host receptor identification of the siphovirus vB_YenS_ϕR2-01 (in short, ϕR2-01) that infects strains of several Yersinia enterocolitica serotypes. The ϕR2-01 genome contains 154 predicted genes, 117 of which encode products that are homologous to those of Escherichia bacteriophage T5. The ϕR2-01 and T5 genomes are largely syntenic, with the major differences residing in areas encoding hypothetical ϕR2-01 proteins. Label-free mass-spectrometry-based proteomics confirmed the expression of 90 of the ϕR2-01 genes, with 88 of these being either phage particle structural or phage-particle-associated proteins. In vitro transposon-based host mutagenesis and ϕR2-01 adsorption experiments identified the outer membrane vitamin B12 receptor BtuB as the host receptor. This study provides a proteogenomic characterization of a T5-type bacteriophage and identifies specific Y. enterocolitica strains sensitive to infection with possible future applications of ϕR2-01 as a food biocontrol or phage therapy agent.}, }
@article {pmid34833893, year = {2021}, author = {Guan, ZW and Yu, EZ and Feng, Q}, title = {Soluble Dietary Fiber, One of the Most Important Nutrients for the Gut Microbiota.}, journal = {Molecules (Basel, Switzerland)}, volume = {26}, number = {22}, pages = {}, pmid = {34833893}, issn = {1420-3049}, support = {81630072//National Natural Science Foundation of China/ ; 82071122//National Natural Science Foundation of China/ ; }, mesh = {Dietary Fiber/*administration &amp; dosage/analysis/*metabolism ; Energy Intake ; Gastrointestinal Microbiome/*physiology ; Histone Deacetylase Inhibitors/administration &amp; dosage/chemistry/metabolism ; Humans ; Intestinal Absorption ; Ligands ; Molecular Structure ; Polysaccharides/administration &amp; dosage/chemistry/metabolism ; Receptors, G-Protein-Coupled/metabolism ; Satiation ; Solubility ; }, abstract = {Dietary fiber is a widely recognized nutrient for human health. Previous studies proved that dietary fiber has significant implications for gastrointestinal health by regulating the gut microbiota. Moreover, mechanistic research showed that the physiological functions of different dietary fibers depend to a great extent on their physicochemical characteristics, one of which is solubility. Compared with insoluble dietary fiber, soluble dietary fiber can be easily accessed and metabolized by fiber-degrading microorganisms in the intestine and produce a series of beneficial and functional metabolites. In this review, we outlined the structures, characteristics, and physiological functions of soluble dietary fibers as important nutrients. We particularly focused on the effects of soluble dietary fiber on human health via regulating the gut microbiota and reviewed their effects on dietary and clinical interventions.}, }
@article {pmid34833140, year = {2021}, author = {Salabura, A and Łuniewski, A and Kucharska, M and Myszak, D and Dołęgowska, B and Ciechanowski, K and Kędzierska-Kapuza, K and Wojciuk, B}, title = {Urinary Tract Virome as an Urgent Target for Metagenomics.}, journal = {Life (Basel, Switzerland)}, volume = {11}, number = {11}, pages = {}, pmid = {34833140}, issn = {2075-1729}, abstract = {Virome-a part of a microbiome-is a term used to describe all viruses found in the specific organism or system. Recently, as new technologies emerged, it has been confirmed that kidneys and the lower urinary tract are colonized not only by the previously described viruses, but also completely novel species. Viruses can be both pathogenic and protective, as they often carry important virulence factors, while at the same time represent anti-inflammatory functions. This paper aims to show and compare the viral species detected in various, specific clinical conditions. Because of the unique characteristics of viruses, new sequencing techniques and databases had to be developed to conduct research on the urinary virome. The dynamic development of research on the human microbiome suggests that the detailed studies on the urinary system virome will provide answers to many questions about the risk factors for civilization, cancer, and autoimmune diseases.}, }
@article {pmid34830161, year = {2021}, author = {Puebla-Barragan, S and Akouris, PP and Al, KF and Carr, C and Lamb, B and Sumarah, M and van der Veer, C and Kort, R and Burton, J and Reid, G}, title = {The Two-Way Interaction between the Molecules That Cause Vaginal Malodour and Lactobacilli: An Opportunity for Probiotics.}, journal = {International journal of molecular sciences}, volume = {22}, number = {22}, pages = {}, pmid = {34830161}, issn = {1422-0067}, support = {692895//Consejo Nacional de Ciencia y Tecnolog&#xed;a/ ; }, mesh = {Dysbiosis/drug therapy/*immunology ; Female ; Humans ; *Lactobacillus/classification/growth &amp; development/isolation &amp; purification ; Probiotics/therapeutic use ; Vagina/*microbiology ; Vaginosis, Bacterial/drug therapy/*microbiology ; }, abstract = {Vaginal malodour is a sign of dysbiosis. The biogenic amines (BAs) cadaverine, putrescine and tyramine are known to be causative compounds. Recent reports suggest these compounds produced by pathogens might have a role beyond causing malodour; namely inhibiting the growth of lactobacilli bacteria that are crucial in the maintenance of vaginal homeostasis. The aim of this study was to identify whether certain lactobacilli strains could reduce BAs and to evaluate how Lactobacillus species were affected by these compounds. Using LC-MS and HPLC-UV, five Lactobacillus crispatus strains were identified as being capable of significantly reducing BAs from the media under in vitro conditions. Through 16S rRNA gene sequencing of vaginal swabs exposed to Bas, cadaverine was found to reduce the relative abundance of lactobacilli. When L. crispatus was exposed to media supplemented with BAs with an HCl adjusted lower pH, its growth was enhanced, demonstrating the relevance of the maintenance of an acidic vaginal environment. If strains are to be developed for probiotic application to alleviate bacterial vaginosis and other conditions affecting large numbers of women worldwide, their ability to adapt to Bas and regulate pH should be part of the experimentation.}, }
@article {pmid34827311, year = {2021}, author = {D'Angeli, F and Guadagni, F and Genovese, C and Nicolosi, D and Trovato Salinaro, A and Spampinato, M and Mannino, G and Lo Furno, D and Petronio Petronio, G and Ronsisvalle, S and Sipala, F and Falzone, L and Calabrese, V}, title = {Anti-Candidal Activity of the Parasitic Plant Orobanche crenata Forssk.}, journal = {Antibiotics (Basel, Switzerland)}, volume = {10}, number = {11}, pages = {}, pmid = {34827311}, issn = {2079-6382}, support = {CUP B66G18000220005//European Social Fund, PNR 2015-2020 ARS01_01163 PerMedNet under the Italian Ministries of Education, University and Research/ ; CUP G88I18000710007//PO FESR 2014-2020 Sicily Region Action 1.1.5, NUVACAL BC/ ; }, abstract = {Candida albicans (C. albicans) and Candida glabrata (C. glabrata) are part of the human microbiome. However, they possess numerous virulence factors, which confer them the ability to cause both local and systemic infections. Candidiasis can involve multiple organs, including the eye. In the present study, we investigated the anti-candidal activity and the re-epithelizing effect of Orobanche crenata leaf extract (OCLE). By the microdilution method, we demonstrated an inhibitory effect of OCLE on both C. albicans and C. glabrata growth. By crystal violet and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, we showed the ability of OCLE to inhibit the biofilm formation and the viability of yeast cells, respectively. By germ tube and adhesion assays, we proved the capacity of OCLE to affect the morphological transition of C. albicans and the adhesion of both pathogens to human retinal pigment epithelial cells (ARPE-19), respectively. Besides, by MTT and wound healing assay, we evaluated the cytotoxic and re-epithelizing effects of OCLE on ARPE-19. Finally, the Folin-Ciocalteu and the ultra-performance liquid chromatography-tandem mass spectrometry revealed a high content of phenols and the presence of several bioactive molecules in the extract. Our results highlighted new properties of O. crenata, useful in the control of Candida infections.}, }
@article {pmid34821456, year = {2022}, author = {Diotallevi, C and Fontana, M and Latimer, C and Ternan, NG and Pourshahidi, LK and Lawther, R and O'Connor, G and Conterno, L and Gasperotti, M and Angeli, A and Lotti, C and Bianchi, M and Vrhovsek, U and Fava, F and Gobbetti, M and Gill, CIR and Tuohy, KM}, title = {Ex Vivo Fecal Fermentation of Human Ileal Fluid Collected After Wild Strawberry Consumption Modulates Human Microbiome Community Structure and Metabolic Output and Protects Against DNA Damage in Colonic Epithelial Cells.}, journal = {Molecular nutrition &amp; food research}, volume = {66}, number = {3}, pages = {e2100405}, doi = {10.1002/mnfr.202100405}, pmid = {34821456}, issn = {1613-4133}, mesh = {Colon/metabolism ; DNA Damage ; Epithelial Cells ; Fermentation ; *Fragaria/chemistry ; Fruit/chemistry ; *Gastrointestinal Microbiome ; Humans ; Kinetics ; }, abstract = {SCOPE: Wild strawberries (Fragaria vesca) are richer in (poly)phenols than common commercial strawberry varieties, e.g., Fragaria × ananassa. (Poly)phenols and their microbiota-derived metabolites are hypothesized to exert bioactivity within the human gut mucosa. To address this, the effects of wild strawberries are investigated with respect to their bioactivity and microbiota-modulating capacity using both in vitro and ex vivo approaches.<br><br>METHODS AND RESULTS: Ileal fluids collected pre- (0h) and post-consumption (8h) of 225&#xa0;g wild strawberries by ileostomates (n = 5) and also in vitro digested strawberry varieties (Fragaria vesca and Fragaria &#xd7; ananassa Duchesne) supernatants are collected. Subsequent fermentation of these supernatants using an in vitro batch culture proximal colon model reveals significant treatment-specific changes in microbiome community structure in terms of alpha but not beta diversity at 24 h. Nutri-kinetic analysis reveals a significant increase in the concentration of gut microbiota catabolites, including 3-(4hydroxyphenyl)propionic acid, 3-(3-hydroxyphenyl)propanoic acid, and benzoic acid. Furthermore, post-berry ileal fermentates (24 h) significantly (p&#xa0;< 0.01) decrease DNA damage (% Tail DNA, COMET assay) in both HT29 cells (&#x223c;45%) and CCD 841 CoN cells (&#x223c;25%) compared to untreated controls.<br><br>CONCLUSIONS: Post berry consumption fermentates exhibit increased overall levels of (poly)phenolic metabolites, which retains their bioactivity, reducing DNA damage in colonocytes.}, }
@article {pmid34820530, year = {2021}, author = {Liang, G}, title = {Altered gut bacterial and metabolic signatures and their interaction in inflammatory bowel disease.}, journal = {Synthetic and systems biotechnology}, volume = {6}, number = {4}, pages = {377-383}, pmid = {34820530}, issn = {2405-805X}, abstract = {Dysregulation of the gut microbiome has been implicated in the progression of many diseases. This study explored the role of microbial and metabolic signatures, and their interaction between the Human inflammatory bowel disease (IBD) and healthy controls (HCs) based on the combination of machine learning and traditional statistical analysis, using data collected from the Human Microbiome Project (HMP) and the Integrative Human Microbiome Project (iHMP). It was showed that the microbial and metabolic signatures of IBD patients were significantly different from those of HCs. Compared to HCs, IBD subjects were characterized by 25 enriched species and 6 depleted species. Furthermore, a total of 17 discriminative pathways were identified between the IBD and HC groups. Those differential pathways were mainly involved in amino acid, nucleotide biosynthesis, and carbohydrate degradation. Notably, co-occurrence network analysis revealed that non-predominant bacteria Ruminococcus_obeum and predominant bacteria Faecalibacterium_prausnitzii formed the same broad and strong co-occurring relationships with pathways. Moreover, the essay identified a combinatorial marker panel that could distinguish IBD from HCs. Receiver Operating Characteristic (ROC) and Decision Curve Analysis (DCA) confirmed the high accuracy (AUC = 0.966) and effectiveness of the model. Meanwhile, an independent cohort used for external validation also showed the identical high efficacy (AUC = 0.835). These findings showed that the gut microbes may be relevant to the pathogenesis and pathophysiology, and offer universal utility as a non-invasive diagnostic test in IBD.}, }
@article {pmid34819672, year = {2021}, author = {Balaich, J and Estrella, M and Wu, G and Jeffrey, PD and Biswas, A and Zhao, L and Korennykh, A and Donia, MS}, title = {The human microbiome encodes resistance to the antidiabetic drug acarbose.}, journal = {Nature}, volume = {600}, number = {7887}, pages = {110-115}, pmid = {34819672}, issn = {1476-4687}, support = {R01 GM110161/GM/NIGMS NIH HHS/United States ; DP2 AI124441/AI/NIAID NIH HHS/United States ; T32 GM007388/GM/NIGMS NIH HHS/United States ; P41 GM111244/GM/NIGMS NIH HHS/United States ; 1013579/WT_/Wellcome Trust/United Kingdom ; }, mesh = {Acarbose/metabolism/*pharmacology ; Amylases/metabolism ; Animals ; Drug Resistance, Bacterial/*drug effects ; Gastrointestinal Microbiome/*drug effects ; Humans ; Hypoglycemic Agents/metabolism/*pharmacology ; *Inactivation, Metabolic ; Metagenome/drug effects/*genetics ; Models, Molecular ; Mouth/drug effects/*microbiology ; Phosphotransferases (Alcohol Group Acceptor)/chemistry/*genetics/metabolism ; }, abstract = {The human microbiome encodes a large repertoire of biochemical enzymes and pathways, most of which remain uncharacterized. Here, using a metagenomics-based search strategy, we discovered that bacterial members of the human gut and oral microbiome encode enzymes that selectively phosphorylate a clinically used antidiabetic drug, acarbose[1,2], resulting in its inactivation. Acarbose is an inhibitor of both human and bacterial α-glucosidases[3], limiting the ability of the target organism to metabolize complex carbohydrates. Using biochemical assays, X-ray crystallography and metagenomic analyses, we show that microbiome-derived acarbose kinases are specific for acarbose, provide their harbouring organism with a protective advantage against the activity of acarbose, and are widespread in the microbiomes of western and non-western human populations. These results provide an example of widespread microbiome resistance to a non-antibiotic drug, and suggest that acarbose resistance has disseminated in the human microbiome as a defensive strategy against a potential endogenous producer of a closely related molecule.}, }
@article {pmid34819600, year = {2021}, author = {Tozzi, AE and Del Chierico, F and Pandolfi, E and Reddel, S and Gesualdo, F and Gardini, S and Guarrasi, V and Russo, L and Croci, I and Campagna, I and Linardos, G and Concato, C and Villani, A and Putignani, L}, title = {Nasopharyngeal microbiota in hospitalized children with Bordetella pertussis and Rhinovirus infection.}, journal = {Scientific reports}, volume = {11}, number = {1}, pages = {22858}, pmid = {34819600}, issn = {2045-2322}, mesh = {Bordetella Infections/diagnosis/*microbiology ; Bordetella pertussis/*isolation &amp; purification ; *Coinfection ; Dysbiosis ; Female ; *Hospitalization ; Host-Pathogen Interactions ; Humans ; Infant ; Male ; Metagenome ; Metagenomics ; Microbiota ; Nasopharynx/*microbiology/*virology ; Picornaviridae Infections/diagnosis/*virology ; Rhinovirus/*isolation &amp; purification ; Ribotyping ; }, abstract = {Despite great advances in describing Bordetella pertussis infection, the role of the host microbiota in pertussis pathogenesis remains unexplored. Indeed, the microbiota plays important role in defending against bacterial and viral respiratory infections. We investigated the nasopharyngeal microbiota in infants infected by B. pertussis (Bp), Rhinovirus (Rv) and simultaneously by both infectious agents (Bp + Rv). We demonstrated a specific nasopharyngeal microbiome profiles for Bp group, compared to Rv and Bp + Rv groups, and a reduction of microbial richness during coinfection compared to the single infections. The comparison amongst the three groups showed the increase of Alcaligenaceae and Achromobacter in Bp and Moraxellaceae and Moraxella in Rv group. Furthermore, correlation analysis between patients' features and nasopharyngeal microbiota profile highlighted a link between delivery and feeding modality, antibiotic administration and B. pertussis infection. A model classification demonstrated a microbiota fingerprinting specific of Bp and Rv infections. In conclusion, external factors since the first moments of life contribute to the alteration of nasopharyngeal microbiota, indeed increasing the susceptibility of the host to the pathogens' infections. When the infection is triggered, the presence of infectious agents modifies the microbiota favoring the overgrowth of commensal bacteria that turn in pathobionts, hence contributing to the disease severity.}, }
@article {pmid34812271, year = {2021}, author = {Wang, Y and Sun, M and Duan, Y}, title = {Metagenomic Sequencing Analysis for Acne Using Machine Learning Methods Adapted to Single or Multiple Data.}, journal = {Computational and mathematical methods in medicine}, volume = {2021}, number = {}, pages = {8008731}, pmid = {34812271}, issn = {1748-6718}, mesh = {Acne Vulgaris/*genetics/metabolism/*microbiology ; Canonical Correlation Analysis ; Case-Control Studies ; Computational Biology ; Face/microbiology ; Humans ; Lipids/analysis/genetics ; *Machine Learning ; *Metagenome ; Metagenomics/statistics &amp; numerical data ; Microbiota/genetics ; Principal Component Analysis ; Skin/chemistry/microbiology ; }, abstract = {The human health status can be assessed by the means of research and analysis of the human microbiome. Acne is a common skin disease whose morbidity increases year by year. The lipids which influence acne to a large extent are studied by metagenomic methods in recent years. In this paper, machine learning methods are used to analyze metagenomic sequencing data of acne, i.e., all kinds of lipids in the face skin. Firstly, lipids data of the diseased skin (DS) samples and the healthy skin (HS) samples of acne patients and the normal control (NC) samples of healthy person are, respectively, analyzed by using principal component analysis (PCA) and kernel principal component analysis (KPCA). Then, the lipids which have main influence on each kind of sample are obtained. In addition, a multiset canonical correlation analysis (MCCA) is utilized to get lipids which can differentiate the face skins of the above three samples. The experimental results show the machine learning methods can effectively analyze metagenomic sequencing data of acne. According to the results, lipids which only influence one of the three samples or the lipids which simultaneously have different degree of influence on these three samples can be used as indicators to judge skin statuses.}, }
@article {pmid34812127, year = {2021}, author = {Depommier, C and Everard, A and Druart, C and Maiter, D and Thissen, JP and Loumaye, A and Hermans, MP and Delzenne, NM and de Vos, WM and Cani, PD}, title = {Serum metabolite profiling yields insights into health promoting effect of A. muciniphila in human volunteers with a metabolic syndrome.}, journal = {Gut microbes}, volume = {13}, number = {1}, pages = {1994270}, pmid = {34812127}, issn = {1949-0984}, mesh = {Adolescent ; Adult ; Aged ; Akkermansia/physiology ; Amino Acids/metabolism ; Carnitine/analogs &amp; derivatives/metabolism ; Glycolysis/drug effects ; Humans ; Insulin Resistance ; Ketone Bodies/metabolism ; Lipid Metabolism/drug effects ; Liver/drug effects/metabolism ; Metabolic Syndrome/blood/*diet therapy ; Metabolome/*drug effects ; Middle Aged ; Probiotics/administration &amp; dosage/*pharmacology ; Young Adult ; }, abstract = {Reduction of A. muciniphila relative abundance in the gut microbiota is a widely accepted signature associated with obesity-related metabolic disorders. Using untargeted metabolomics profiling of fasting plasma, our study aimed at identifying metabolic signatures associated with beneficial properties of alive and pasteurized A. muciniphila when administrated to a cohort of insulin-resistant individuals with metabolic syndrome. Our data highlighted either shared or specific alterations in the metabolome according to the form of A. muciniphila administered with respect to a control group. Common responses encompassed modulation of amino acid metabolism, characterized by reduced levels of arginine and alanine, alongside several intermediates of tyrosine, phenylalanine, tryptophan, and glutathione metabolism. The global increase in levels of acylcarnitines together with specific modulation of acetoacetate also suggested induction of ketogenesis through enhanced β-oxidation. Moreover, our data pinpointed some metabolites of interest considering their emergence as substantial compounds pertaining to health and diseases in the more recent literature.}, }
@article {pmid34806323, year = {2022}, author = {Allen, NG and Edupuganti, L and Edwards, DJ and Jimenez, NR and Buck, GA and Jefferson, KK and Strauss, JF and ,  and Wickham, EP and Fettweis, JM}, title = {The vaginal microbiome in women of reproductive age with healthy weight versus overweight/obesity.}, journal = {Obesity (Silver Spring, Md.)}, volume = {30}, number = {1}, pages = {142-152}, pmid = {34806323}, issn = {1930-739X}, support = {UH3AI083263//Foundation for the National Institutes of Health/ ; R21 HD092965/HD/NICHD NIH HHS/United States ; R21HD092965//Foundation for the National Institutes of Health/ ; UH3 AI083263/AI/NIAID NIH HHS/United States ; R25 GM090084/GM/NIGMS NIH HHS/United States ; UL1 TR002649/TR/NCATS NIH HHS/United States ; R25GM090084//Foundation for the National Institutes of Health/ ; U54 HD080784/HD/NICHD NIH HHS/United States ; U54HD080784//Foundation for the National Institutes of Health/ ; }, mesh = {Adult ; Case-Control Studies ; Female ; Humans ; Infant, Newborn ; *Microbiota ; Obesity ; Overweight ; *Premature Birth ; RNA, Ribosomal, 16S/genetics ; }, abstract = {OBJECTIVE: The aim of this study was to evaluate the differences between the vaginal microbiome of reproductive-aged women with overweight and obesity (Ow/Ob) compared with healthy weight (HW).<br><br>METHODS: In this case-control study, a cohort of 367 nonpregnant women (18 to 40 years) with Ow/Ob (BMI &#x2265;25 kg/m[2]) was case-matched with 367 women with HW (BMI 18.0 to 24.9 kg/m[2]). The study was a secondary analysis of 16S rRNA vaginal microbiome surveys through the Vaginal Human Microbiome Study (VaHMP).&#xa0;Groups were matched on age, race/ethnicity, income, and nulliparity status.<br><br>RESULTS: Mean age and BMI of Ow/Ob and HW groups were 26.8 versus 26.7 years and 37.0 versus 22.1 kg/m[2] , respectively. The overall vaginal microbiome composition differed between&#xa0;groups (PERMANOVA, p = 0.035). Women with Ow/Ob had higher alpha diversity compared with women with HW (Wilcoxon test, Shannon index p = 0.025; inverse Simpson index p = 0.026). Lactobacillus&#xa0;dominance (&#x2265;30% proportional abundance) was observed in a greater proportion of women with HW (48.7%) compared with Ow/Ob (40.1%; p = 0.026).<br><br>CONCLUSIONS: The vaginal microbiome differs in reproductive-aged women with Ow/Ob compared with women with HW, with increased alpha diversity and decreased predominance of Lactobacillus. Observed differences in the vaginal microbiome may partially explain differences in preterm birth and bacterial vaginosis risk between these populations.}, }
@article {pmid34803517, year = {2021}, author = {Amedei, A and Capasso, C and Nannini, G and Supuran, CT}, title = {Microbiota, Bacterial Carbonic Anhydrases, and Modulators of Their Activity: Links to Human Diseases?.}, journal = {Mediators of inflammation}, volume = {2021}, number = {}, pages = {6926082}, pmid = {34803517}, issn = {1466-1861}, mesh = {Anti-Bacterial Agents/pharmacology ; Bacteria/*enzymology ; Carbonic Anhydrase Inhibitors/pharmacology ; Carbonic Anhydrases/*physiology ; Dysbiosis/etiology ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/*physiology ; Humans ; Prebiotics ; Probiotics/pharmacology ; Synbiotics ; }, abstract = {The involvement of the human microbiome is crucial for different host functions such as protection, metabolism, reproduction, and especially immunity. However, both endogenous and exogenous factors can affect the balance of the microbiota, creating a state of dysbiosis, which can start various gastrointestinal or systemic diseases. The challenge of future medicine is to remodel the intestinal microbiota to bring it back to healthy equilibrium (eubiosis) and, thus, counteract its negative role in the diseases' onset. The shaping of the microbiota is currently practiced in different ways ranging from diet (or use of prebiotics, probiotics, and synbiotics) to phage therapy and antibiotics, including microbiota fecal transplantation. Furthermore, because microbiota modulation is a capillary process, and because many microbiota bacteria (both beneficial and pathogenic) have carbonic anhydrases (specifically the four classes α, β, γ, and ι), we believe that the use of CA inhibitors and activators can open up new therapeutic strategies for many diseases associated with microbial dysbiosis, such as the various gastrointestinal disorders and the same colorectal cancer.}, }
@article {pmid34796006, year = {2021}, author = {Belova, IV and Khrulev, AE and Tochilina, AG and Khruleva, NS and Lobanova, NA and Zhirnov, VA and Molodtsova, SB and Lobanov, VN and Solovieva, IV}, title = {Colon Microbiocenosis and Its Correction in Patients Receiving Programmed Hemodialysis.}, journal = {Sovremennye tekhnologii v meditsine}, volume = {12}, number = {5}, pages = {62-68}, pmid = {34796006}, issn = {2309-995X}, mesh = {Colon/microbiology ; Dysbiosis/microbiology ; Humans ; *Quality of Life ; Renal Dialysis/adverse effects ; *Synbiotics ; }, abstract = {UNLABELLED: The aim of the investigation was to study the species composition of colon microbiocenosis in patients with chronic kidney disease receiving programmed hemodialysis treatment and to evaluate the efficacy of its correction using a new immobilized synbiotic.<br><br>MATERIALS AND METHODS: Samples of colon microbiota from 62 patients undergoing programmed hemodialysis were studied before and after a course of diet therapy that included probiotic components, in particular, the immobilized synbiotic LB-complex L. Isolation of microorganisms was carried out according to our original method; for bacteria identification, a MALDI-TOF Autoflex speed mass spectrometer (Bruker Daltonik, Germany) was used in the Biotyper program mode. The results were assessed using the criteria proposed by the authors and based on the OST 91500.11.0004-2003. The efficacy of the immobilized synbiotic was determined based on the clinical data, questionnaires, and bacteriological tests.<br><br>RESULTS: In patients receiving programmed hemodialysis (before the start of the diet therapy), chronic moderate inflammation and azotemia were found. Dysbiotic changes in microbiocenosis were revealed in all the examined patients; in the absence or suppression of lacto- and bifidoflora, the number and diversity of Bacteroides spp., Clostridium spp., Collinsella spp., Eggerthella spp. and other bacteria increased, which was consistent with the theory of functional redundancy of gut microbiota. From the answers to the questionnaires, a decrease in the quality of life was found (up to 70 points out of 100) according to six of the eight scales used. After the combined therapy using the synbiotic LB-complex L in the study group, 56% of the examined patients showed their microbiocenosis restored to normal; no grade III dysbiosis was detected in any patient. There was a significant decrease in CRP and ESR in these patients and an improvement in the quality of life by criteria reflecting physical health.<br><br>CONCLUSION: In patients receiving programmed hemodialysis, the addition of a probiotic component in the diet therapy restores the evolutionarily determined structure of the microbiocenosis, normalizes its functions, and leads to an overall improvement in health and quality of life.}, }
@article {pmid34789871, year = {2021}, author = {Mirzayi, C and Renson, A and ,  and ,  and Zohra, F and Elsafoury, S and Geistlinger, L and Kasselman, LJ and Eckenrode, K and van de Wijgert, J and Loughman, A and Marques, FZ and MacIntyre, DA and Arumugam, M and Azhar, R and Beghini, F and Bergstrom, K and Bhatt, A and Bisanz, JE and Braun, J and Bravo, HC and Buck, GA and Bushman, F and Casero, D and Clarke, G and Collado, MC and Cotter, PD and Cryan, JF and Demmer, RT and Devkota, S and Elinav, E and Escobar, JS and Fettweis, J and Finn, RD and Fodor, AA and Forslund, S and Franke, A and Furlanello, C and Gilbert, J and Grice, E and Haibe-Kains, B and Handley, S and Herd, P and Holmes, S and Jacobs, JP and Karstens, L and Knight, R and Knights, D and Koren, O and Kwon, DS and Langille, M and Lindsay, B and McGovern, D and McHardy, AC and McWeeney, S and Mueller, NT and Nezi, L and Olm, M and Palm, N and Pasolli, E and Raes, J and Redinbo, MR and Rühlemann, M and Balfour Sartor, R and Schloss, PD and Schriml, L and Segal, E and Shardell, M and Sharpton, T and Smirnova, E and Sokol, H and Sonnenburg, JL and Srinivasan, S and Thingholm, LB and Turnbaugh, PJ and Upadhyay, V and Walls, RL and Wilmes, P and Yamada, T and Zeller, G and Zhang, M and Zhao, N and Zhao, L and Bao, W and Culhane, A and Devanarayan, V and Dopazo, J and Fan, X and Fischer, M and Jones, W and Kusko, R and Mason, CE and Mercer, TR and Sansone, SA and Scherer, A and Shi, L and Thakkar, S and Tong, W and Wolfinger, R and Hunter, C and Segata, N and Huttenhower, C and Dowd, JB and Jones, HE and Waldron, L}, title = {Reporting guidelines for human microbiome research: the STORMS checklist.}, journal = {Nature medicine}, volume = {27}, number = {11}, pages = {1885-1892}, pmid = {34789871}, issn = {1546-170X}, support = {R01 GM135218/GM/NIGMS NIH HHS/United States ; R01 DK085025/DK/NIDDK NIH HHS/United States ; BB/E025080/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; P30 DK098722/DK/NIDDK NIH HHS/United States ; R01 CA230551/CA/NCI NIH HHS/United States ; U01 CA230551/CA/NCI NIH HHS/United States ; }, mesh = {Computational Biology/*methods ; Dysbiosis/*microbiology ; Humans ; Microbiota/*physiology ; Observational Studies as Topic/*methods ; *Research Design ; Translational Science, Biomedical ; }, abstract = {The particularly interdisciplinary nature of human microbiome research makes the organization and reporting of results spanning epidemiology, biology, bioinformatics, translational medicine and statistics a challenge. Commonly used reporting guidelines for observational or genetic epidemiology studies lack key features specific to microbiome studies. Therefore, a multidisciplinary group of microbiome epidemiology researchers adapted guidelines for observational and genetic studies to culture-independent human microbiome studies, and also developed new reporting elements for laboratory, bioinformatics and statistical analyses tailored to microbiome studies. The resulting tool, called 'Strengthening The Organization and Reporting of Microbiome Studies' (STORMS), is composed of a 17-item checklist organized into six sections that correspond to the typical sections of a scientific publication, presented as an editable table for inclusion in supplementary materials. The STORMS checklist provides guidance for concise and complete reporting of microbiome studies that will facilitate manuscript preparation, peer review, and reader comprehension of publications and comparative analysis of published results.}, }
@article {pmid34785217, year = {2022}, author = {Mousavi, SE and Delgado-Saborit, JM and Adivi, A and Pauwels, S and Godderis, L}, title = {Air pollution and endocrine disruptors induce human microbiome imbalances: A systematic review of recent evidence and possible biological mechanisms.}, journal = {The Science of the total environment}, volume = {816}, number = {}, pages = {151654}, doi = {10.1016/j.scitotenv.2021.151654}, pmid = {34785217}, issn = {1879-1026}, support = {MR/S019669/1/MRC_/Medical Research Council/United Kingdom ; }, mesh = {*Air Pollution/statistics &amp; numerical data ; Dysbiosis ; *Endocrine Disruptors/toxicity ; Female ; *Gastrointestinal Microbiome ; Humans ; *Microbiota ; }, abstract = {A rich body of literature indicates that environmental factors interact with the human microbiome and influence its composition and functions contributing to the pathogenesis of diseases in distal sites of the body. This systematic review examines the scientific evidence on the effect of environmental toxicants, air pollutants and endocrine disruptors (EDCs), on compositional and diversity of human microbiota. Articles from PubMed, Embase, WoS and Google Scholar where included if they focused on human populations or the SHIME® model, and assessed the effects of air pollutants and EDCs on human microbiome. Non-human studies, not written in English and not displaying original research were excluded. The Newcastle-Ottawa Scale was used to assess the quality of individual studies. Results were extracted and presented in tables. 31 studies were selected, including 24 related to air pollutants, 5 related to EDCs, and 2 related to EDC using the SHIME® model. 19 studies focussed on the respiratory system (19), gut (8), skin (2), vaginal (1) and mammary (1) microbiomes. No sufficient number of studies are available to observe a consistent trend for most of the microbiota, except for streptococcus and veillionellales for which 9 out of 10, and 3 out of 4 studies suggest an increase of abundance with exposure to air pollution. A limitation of the evidence reviewed is the scarcity of existing studies assessing microbiomes from individual systems. Growing evidence suggests that exposure to environmental contaminants could change the diversity and abundance of resident microbiota, e.g. in the upper and lower respiratory, gastrointestinal, and female reproductive system. Microbial dysbiosis might lead to colonization of pathogens and outgrowth of pathobionts facilitating infectious diseases. It also might prime metabolic dysfunctions disrupting the production of beneficial metabolites. Further studies should elucidate the role of environmental pollutants in the development of dysbiosis and dysregulation of microbiota-related immunological processes.}, }
@article {pmid34784956, year = {2021}, author = {Romito, I and Porru, M and Braghini, MR and Pompili, L and Panera, N and Crudele, A and Gnani, D and De Stefanis, C and Scarsella, M and Pomella, S and Levi Mortera, S and de Billy, E and Conti, AL and Marzano, V and Putignani, L and Vinciguerra, M and Balsano, C and Pastore, A and Rota, R and Tartaglia, M and Leonetti, C and Alisi, A}, title = {Focal adhesion kinase inhibitor TAE226 combined with Sorafenib slows down hepatocellular carcinoma by multiple epigenetic effects.}, journal = {Journal of experimental &amp; clinical cancer research : CR}, volume = {40}, number = {1}, pages = {364}, pmid = {34784956}, issn = {1756-9966}, support = {MFAG12936//Associazione Italiana per la Ricerca sul Cancro/ ; }, mesh = {Animals ; Antineoplastic Combined Chemotherapy Protocols/pharmacology/*therapeutic use ; Carcinoma, Hepatocellular/*drug therapy ; Cell Line, Tumor ; Cell Proliferation ; Epigenesis, Genetic/*genetics ; Humans ; Liver Neoplasms/*drug therapy ; Male ; Mice ; Mice, Inbred NOD ; Morpholines/pharmacology/*therapeutic use ; Sorafenib/pharmacology/*therapeutic use ; }, abstract = {BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common and lethal malignant tumours worldwide. Sorafenib (SOR) is one of the most effective single-drug systemic therapy against advanced HCC, but the identification of novel combination regimens for a continued improvement in overall survival is a big challenge. Recent studies highlighted the crucial role of focal adhesion kinase (FAK) in HCC growth. The aim of this study was to investigate the antitumor effects of three different FAK inhibitors (FAKi), alone or in combination with SOR, using in vitro and in vivo models of HCC.<br><br>METHODS: The effect of PND1186, PF431396, TAE226 on cell viability was compared to SOR. Among them TAE226, emerging as the most effective FAKi, was tested alone or in combination with SOR using 2D/3D human HCC cell line cultures and HCC xenograft murine models. The mechanisms of action were assessed by gene/protein expression and imaging approaches, combined with high-throughput methods.<br><br>RESULTS: TAE226 was the more effective FAKi to be combined with SOR against HCC. Combined TAE226 and SOR treatment reduced HCC growth both in vitro and in vivo by affecting tumour-promoting gene expression and inducing epigenetic changes via dysregulation of FAK nuclear interactome. We characterized a novel nuclear functional interaction between FAK and the NuRD complex. TAE226-mediated FAK depletion and SOR-promoted MAPK down-modulation caused a decrease in the nuclear amount of HDAC1/2 and a consequent increase of the histone H3 lysine 27 acetylation, thus counteracting histone H3 lysine 27 trimethylation.<br><br>CONCLUSIONS: Altogether, our findings provide the first evidence that TAE226 combined with SOR efficiently reduces HCC growth in vitro and in vivo. Also, our data highlight that deep analysis of FAK nuclear interactome may lead to the identification of new promising targets for HCC therapy.}, }
@article {pmid34784344, year = {2021}, author = {Mallick, H and Rahnavard, A and McIver, LJ and Ma, S and Zhang, Y and Nguyen, LH and Tickle, TL and Weingart, G and Ren, B and Schwager, EH and Chatterjee, S and Thompson, KN and Wilkinson, JE and Subramanian, A and Lu, Y and Waldron, L and Paulson, JN and Franzosa, EA and Bravo, HC and Huttenhower, C}, title = {Multivariable association discovery in population-scale meta-omics studies.}, journal = {PLoS computational biology}, volume = {17}, number = {11}, pages = {e1009442}, pmid = {34784344}, issn = {1553-7358}, support = {U54 DK102557/DK/NIDDK NIH HHS/United States ; P30 DK043351/DK/NIDDK NIH HHS/United States ; U19 AI110820/AI/NIAID NIH HHS/United States ; R01 HG005220/HG/NHGRI NIH HHS/United States ; R24 DK110499/DK/NIDDK NIH HHS/United States ; }, mesh = {*Computational Biology ; Computer Simulation ; *Gastrointestinal Microbiome ; Humans ; Inflammatory Bowel Diseases/genetics/metabolism/pathology ; *Multivariate Analysis ; }, abstract = {It is challenging to associate features such as human health outcomes, diet, environmental conditions, or other metadata to microbial community measurements, due in part to their quantitative properties. Microbiome multi-omics are typically noisy, sparse (zero-inflated), high-dimensional, extremely non-normal, and often in the form of count or compositional measurements. Here we introduce an optimized combination of novel and established methodology to assess multivariable association of microbial community features with complex metadata in population-scale observational studies. Our approach, MaAsLin 2 (Microbiome Multivariable Associations with Linear Models), uses generalized linear and mixed models to accommodate a wide variety of modern epidemiological studies, including cross-sectional and longitudinal designs, as well as a variety of data types (e.g., counts and relative abundances) with or without covariates and repeated measurements. To construct this method, we conducted a large-scale evaluation of a broad range of scenarios under which straightforward identification of meta-omics associations can be challenging. These simulation studies reveal that MaAsLin 2's linear model preserves statistical power in the presence of repeated measures and multiple covariates, while accounting for the nuances of meta-omics features and controlling false discovery. We also applied MaAsLin 2 to a microbial multi-omics dataset from the Integrative Human Microbiome (HMP2) project which, in addition to reproducing established results, revealed a unique, integrated landscape of inflammatory bowel diseases (IBD) across multiple time points and omics profiles.}, }
@article {pmid34778069, year = {2021}, author = {Wang, Y and Guo, H and Gao, X and Wang, J}, title = {The Intratumor Microbiota Signatures Associate With Subtype, Tumor Stage, and Survival Status of Esophageal Carcinoma.}, journal = {Frontiers in oncology}, volume = {11}, number = {}, pages = {754788}, pmid = {34778069}, issn = {2234-943X}, abstract = {Altered human microbiome characteristic has been linked with esophageal carcinoma (ESCA), analysis of microbial profiling directly derived from ESCA tumor tissue is beneficial for studying the microbial functions in tumorigenesis and development of ESCA. In this study, we identified the intratumor microbiome signature and investigated the correlation between microbes and clinical characteristics of patients with ESCA, on the basis of data and information obtained from The Cancer Microbiome Atlas (TCMA) and The Cancer Genome Atlas (TCGA) databases. A total of 82 samples were analyzed for microbial composition at various taxonomic levels, including 40 tumor samples of esophageal squamous cell carcinoma (ESCC), 20 tumor samples of esophageal adenocarcinoma (EAD), and 22 adjacent normal samples. The results showed that the relative abundance of several microbes changed in tumors compared to their paired normal tissues, such as Firmicutes increased significantly while Proteobacteria decreased in tumor samples. We also identified a microbial signature composed of ten microbes that may help in the classification of ESCC and EAD, the two subtypes of ESCA. Correlation analysis demonstrated that compositions of microbes Fusobacteria/Fusobacteriia/Fusobacteriales, Lactobacillales/Lactobacillaceae/Lactobacillus, Clostridia/Clostridiales, Proteobacteria, and Negativicutes were correlated with the clinical characteristics of ESCA patients. In summary, this study supports the feasibility of detecting intratumor microbial composition derived from tumor sequencing data, and it provides novel insights into the roles of microbiota in tumors. Ultimately, as the second genome of human body, microbiome signature analysis may help to add more information to the blueprint of human biology.}, }
@article {pmid34771614, year = {2021}, author = {Amatya, SB and Salmi, S and Kainulainen, V and Karihtala, P and Reunanen, J}, title = {Bacterial Extracellular Vesicles in Gastrointestinal Tract Cancer: An Unexplored Territory.}, journal = {Cancers}, volume = {13}, number = {21}, pages = {}, pmid = {34771614}, issn = {2072-6694}, abstract = {Bacterial extracellular vesicles are membrane-enclosed, lipid bi-layer nanostructures that carry different classes of biomolecules, such as nucleic acids, lipids, proteins, and diverse types of small molecular metabolites, as their cargo. Almost all of the bacteria in the gut secrete extracellular vesicles to assist them in competition, survival, material exchange, host immune modulation, infection, and invasion. The role of gut microbiota in the development, progression, and pathogenesis of gastrointestinal tract (GIT) cancer has been well documented. However, the possible involvement of bacterial extracellular vesicles (bEVs) in GIT cancer pathophysiology has not been given due attention. Studies have illustrated the ability of bEVs to cross physiological barriers, selectively accumulate near tumor cells, and possibly alter the tumor microenvironment (TME). A systematic search of original published works related to bacterial extracellular vesicles on gastrointestinal cancer was performed for this review. The current systemic review outlines the possible impact of gut microbiota derived bEVs in GIT cancer in light of present-day understanding. The necessity of using advanced sequencing technologies, such as genetic, proteomic, and metabolomic investigation methodologies, to facilitate an understanding of the interrelationship between cancer-associated bacterial vesicles and gastrointestinal cancer is also emphasized. We further discuss the clinical and pharmaceutical potential of bEVs, along with future efforts needed to understand the mechanism of interaction of bEVs in GIT cancer pathogenesis.}, }
@article {pmid34768350, year = {2021}, author = {Tourelle, KM and Boutin, S and Weigand, MA and Schmitt, FCF}, title = {Sepsis and the Human Microbiome. Just Another Kind of Organ Failure? A Review.}, journal = {Journal of clinical medicine}, volume = {10}, number = {21}, pages = {}, pmid = {34768350}, issn = {2077-0383}, abstract = {Next-generation sequencing (NGS) has been further optimised during the last years and has given us new insights into the human microbiome. The 16S rDNA sequencing, especially, is a cheap, fast, and reliable method that can reveal significantly more microorganisms compared to culture-based diagnostics. It might be a useful method for patients suffering from severe sepsis and at risk of organ failure because early detection and differentiation between healthy and harmful microorganisms are essential for effective therapy. In particular, the gut and lung microbiome in critically ill patients have been probed by NGS. For this review, an iterative approach was used. Current data suggest that an altered microbiome with a decreased alpha-diversity compared to healthy individuals could negatively influence the individual patient's outcome. In the future, NGS may not only contribute to the diagnosis of complications. Patients at risk could also be identified before surgery or even during their stay in an intensive care unit. Unfortunately, there is still a lack of knowledge to make precise statements about what constitutes a healthy microbiome, which patients exactly have an increased perioperative risk, and what could be a possible therapy to strengthen the microbiome. This work is an iterative review that presents the current state of knowledge in this field.}, }
@article {pmid34763095, year = {2022}, author = {Levi Mortera, S and Vernocchi, P and Basadonne, I and Zandonà, A and Chierici, M and Durighello, M and Marzano, V and Gardini, S and Gasbarrini, A and Urbani, A and Vicari, S and Roncada, P and Furlanello, C and Venuti, P and Putignani, L}, title = {A metaproteomic-based gut microbiota profiling in children affected by autism spectrum disorders.}, journal = {Journal of proteomics}, volume = {251}, number = {}, pages = {104407}, doi = {10.1016/j.jprot.2021.104407}, pmid = {34763095}, issn = {1876-7737}, mesh = {Aged ; *Autism Spectrum Disorder/complications/metabolism ; Child ; Chromatography, Liquid ; *Gastrointestinal Microbiome/physiology ; Humans ; RNA, Ribosomal, 16S/genetics ; Tandem Mass Spectrometry ; }, abstract = {During the last decade, the evidences on the relationship between neurodevelopmental disorders and the microbial communities of the intestinal tract have considerably grown. Particularly, the role of gut microbiota (GM) ecology and predicted functions in Autism Spectrum Disorders (ASD) has been especially investigated by 16S rRNA targeted and shotgun metagenomics, trying to assess disease signature and their correlation with cognitive impairment or gastrointestinal (GI) manifestations of the disease. Herein we present a metaproteomic approach to point out the microbial gene expression profiles, their functional annotations, and the taxonomic distribution of gut microbial communities in ASD children. We pursued a LC-MS/MS based investigation, to compare the GM profiles of patients with those of their respective relatives and aged-matched controls, providing a quantitative evaluation of bacterial metaproteins by SWATH analysis. All data were managed by a multiple step bioinformatic pipeline, including network analysis. In particular, comparing ASD subjects with CTRLs, up-regulation was found for some metaproteins associated with Clostridia and with carbohydrate metabolism (glyceraldehyde-3-phosphate and glutamate dehydrogenases), while down-regulation was observed for others associated with Bacteroidia (SusC and SusD family together with the TonB dependent receptor). Moreover, network analysis highlighted specific microbial correlations among ASD subgroups characterized by different functioning levels and GI symptoms. SIGNIFICANCE: To the best of our knowledge, this study represents the first metaproteomic investigation on the gut microbiota of ASD children compared with relatives and age-matched CTRLs. Remarkably, the applied SWATH methodology allowed the attribution of differentially regulated functions to specific microbial taxa, offering a novel and complementary point of view with respect to previous studies.}, }
@article {pmid34754133, year = {2022}, author = {Maslennikov, R and Ivashkin, V and Ufimtseva, A and Poluektova, E}, title = {[Two consecutive attacks of diarrhea in 15 COVID-19 patients: An antibiotic-associated one following the viral one].}, journal = {Revista de gastroenterologia de Mexico}, volume = {87}, number = {1}, pages = {59-62}, pmid = {34754133}, issn = {0375-0906}, abstract = {Of the 971 patients admitted to our Clinic with suspected COVID-19, 15 (1.5%) presented with two consecutive attacks of diarrhea. One of those patients (a 47-year-old woman) required admission to the intensive care unit and mechanical ventilation. She died on the 11th day of hospitalization (18th day of illness). The first attack of diarrhea in those patients occurred on the 6 th (4th-7th) day of disease and lasted 3 (3-5) days. The second attack of diarrhea developed 11 (8-12) days after the initial onset of diarrhea. Despite the existing trend, the difference in the duration of the diarrhea and the maximum number of bowel movements per day between the first and second attacks was not statistically significant (p = 0.130; p = 0.328). There was no significant difference between the patients with a double attack of diarrhea and those with no diarrhea, regarding the results of the complete blood count, biochemical blood tests, and inflammation biomarkers.}, }
@article {pmid34752448, year = {2021}, author = {Devlin, SM and Martin, A and Ostrovnaya, I}, title = {Identifying prognostic pairwise relationships among bacterial species in microbiome studies.}, journal = {PLoS computational biology}, volume = {17}, number = {11}, pages = {e1009501}, pmid = {34752448}, issn = {1553-7358}, support = {P30 CA008748/CA/NCI NIH HHS/United States ; }, mesh = {*Algorithms ; Bacteria/classification/*genetics/isolation &amp; purification ; Case-Control Studies ; Computational Biology ; Computer Simulation ; Databases, Genetic ; Host Microbial Interactions/genetics/physiology ; Humans ; Logistic Models ; Microbiota/*genetics/*physiology ; Mouth Neoplasms/microbiology ; Prognosis ; RNA, Ribosomal, 16S/genetics ; Software ; Species Specificity ; }, abstract = {In recent literature, the human microbiome has been shown to have a major influence on human health. To investigate this impact, scientists study the composition and abundance of bacterial species, commonly using 16S rRNA gene sequencing, among patients with and without a disease or condition. Methods for such investigations to date have focused on the association between individual bacterium and an outcome, and higher-order pairwise relationships or interactions among bacteria are often avoided due to the substantial increase in dimension and the potential for spurious correlations. However, overlooking such relationships ignores the environment of the microbiome, where there is dynamic cooperation and competition among bacteria. We present a method for identifying and ranking pairs of bacteria that have a differential dichotomized relationship across outcomes. Our approach, implemented in an R package PairSeek, uses the stability selection framework with data-driven dichotomized forms of the pairwise relationships. We illustrate the properties of the proposed method using a published oral cancer data set and a simulation study.}, }
@article {pmid34747338, year = {2021}, author = {van der Vossen, EWJ and Bastos, D and Stols-Gonçalves, D and de Goffau, MC and Davids, M and Pereira, JPB and Li Yim, AYF and Henneman, P and Netea, MG and de Vos, WM and de Jonge, W and Groen, AK and Nieuwdorp, M and Levin, E}, title = {Effects of fecal microbiota transplant on DNA methylation in subjects with metabolic syndrome.}, journal = {Gut microbes}, volume = {13}, number = {1}, pages = {1993513}, pmid = {34747338}, issn = {1949-0984}, mesh = {Adult ; Aged ; DNA Methylation ; *Fecal Microbiota Transplantation ; Female ; Gastrointestinal Microbiome ; Humans ; Insulin Resistance ; Male ; Metabolic Syndrome/genetics/metabolism/microbiology/*therapy ; Microfilament Proteins/genetics/metabolism ; Middle Aged ; Young Adult ; }, abstract = {Accumulating evidence shows that microbes with their theater of activity residing within the human intestinal tract (i.e., the gut microbiome) influence host metabolism. Some of the strongest results come from recent fecal microbial transplant (FMT) studies that relate changes in intestinal microbiota to various markers of metabolism as well as the pathophysiology of insulin resistance. Despite these developments, there is still a limited understanding of the multitude of effects associated with FMT on the general physiology of the host, beyond changes in gut microbiome composition. We examined the effect of either allogenic (lean donor) or autologous FMTs on the gut microbiome, plasma metabolome, and epigenomic (DNA methylation) reprogramming in peripheral blood mononuclear cells in individuals with metabolic syndrome measured at baseline (pre-FMT) and after 6 weeks (post-FMT). Insulin sensitivity was determined with a stable isotope-based 2 step hyperinsulinemic clamp and multivariate machine learning methodology was used to uncover discriminative microbes, metabolites, and DNA methylation loci. A larger gut microbiota shift was associated with an allogenic than with autologous FMT. Furthemore, the data results of the the allogenic FMT group data indicates that the introduction of new species can potentially modulate the plasma metabolome and (as a result) the epigenome. Most notably, the introduction of Prevotella ASVs directly correlated with methylation of AFAP1, a gene involved in mitochondrial function, insulin sensitivity, and peripheral insulin resistance (Rd, rate of glucose disappearance). FMT was found to have notable effects on the gut microbiome but also on the host plasma metabolome and the epigenome of immune cells providing new avenues of inquiry in the context of metabolic syndrome treatment for the manipulation of host physiology to achieve improved insulin sensitivity.}, }
@article {pmid34742104, year = {2022}, author = {Yan, Y and Li, H and Fayyaz, A and Gai, Y}, title = {Metagenomic and network analysis revealed wide distribution of antibiotic resistance genes in monkey gut microbiota.}, journal = {Microbiological research}, volume = {254}, number = {}, pages = {126895}, doi = {10.1016/j.micres.2021.126895}, pmid = {34742104}, issn = {1618-0623}, mesh = {Animals ; Anti-Bacterial Agents/pharmacology ; *Drug Resistance, Microbial/genetics ; *Gastrointestinal Microbiome/drug effects/genetics ; *Haplorhini/microbiology ; Metagenomics ; }, abstract = {The emergence and spread of drug-resistant microorganisms that have acquired new resistance mechanisms, leading to antibiotic resistance, continue to threaten the health of humans and animals worldwide. Non-human primates (NHPs), as close living relatives of human beings in the world, have a high degree of genetic and physiological similarity to humans. However, despite its importance, we lack a comprehensive characterization or understanding of the similarities and differences of the antibiotic resistance genes of the gut microbiome carried by non-human primates and humans. In the present study, the diversity and abundance of antibiotic resistance genes carried by the gut microbiota of cynomolgus monkeys (Macaca fascicularis) were investigated by metagenomic analysis. In total, 60 resistance types conferring resistance to 11 categories of antibiotics were identified in the gut microbiome of cynomolgus monkeys. Interestingly, the composition and abundance of ARGs carried by the gut microbiota of cynomolgus monkeys can be significantly affected by dietary changes. Moreover, we found that all ARG types carried by humans are also present in cynomolgus monkeys. The tetracycline resistance gene tet(37) is evolutionarily conserved and highly homologous. Taken together, our study provides a comprehensive overview of the diversity and richness of ARGs in the gut microbiota of cynomolgus monkeys and underlines the potentially crucial role of diet in the gut health of monkeys and humans.}, }
@article {pmid34742094, year = {2022}, author = {Díez López, C and Vidaki, A and Kayser, M}, title = {Integrating the human microbiome in the forensic toolkit: Current bottlenecks and future solutions.}, journal = {Forensic science international. Genetics}, volume = {56}, number = {}, pages = {102627}, doi = {10.1016/j.fsigen.2021.102627}, pmid = {34742094}, issn = {1878-0326}, mesh = {Computational Biology ; DNA/genetics ; Forensic Medicine ; High-Throughput Nucleotide Sequencing ; Humans ; *Microbiota ; }, abstract = {Over the last few years, advances in massively parallel sequencing technologies (also referred to next generation sequencing) and bioinformatics analysis tools have boosted our knowledge on the human microbiome. Such insights have brought new perspectives and possibilities to apply human microbiome analysis in many areas, particularly in medicine. In the forensic field, the use of microbial DNA obtained from human materials is still in its infancy but has been suggested as a potential alternative in situations when other human (non-microbial) approaches present limitations. More specifically, DNA analysis of a wide variety of microorganisms that live in and on the human body offers promises to answer various forensically relevant questions, such as post-mortem interval estimation, individual identification, and tissue/body fluid identification, among others. However, human microbiome analysis currently faces significant challenges that need to be considered and overcome via future forensically oriented human microbiome research to provide the necessary solutions. In this perspective article, we discuss the most relevant biological, technical and data-related issues and propose future solutions that will pave the way towards the integration of human microbiome analysis in the forensic toolkit.}, }
@article {pmid34742036, year = {2021}, author = {Stockdale, SR and Hill, C}, title = {Progress and prospects of the healthy human gut virome.}, journal = {Current opinion in virology}, volume = {51}, number = {}, pages = {164-171}, doi = {10.1016/j.coviro.2021.10.001}, pmid = {34742036}, issn = {1879-6265}, mesh = {*Health ; Humans ; Intestines/*virology ; Metagenomics ; *Virome/genetics ; Viruses/genetics/*isolation &amp; purification ; }, abstract = {Not all viruses associated with humans cause disease. Non-pathogenic human-infecting viruses are predicted as important for immune system induction and preparation. Phages that infect bacteria are the most abundant predators of the human microbial ecosystem, promoting and maintaining bacterial diversity. Metagenomic analyses of the human gut virome and microbiome are unravelling the intricate predator-prey dynamics of phage-bacteria co-existence, co-evolution, and their interplay with the human host. While most adults harbour a distinctly individualistic and persistent community of virulent phages, new-borns are dominated by temperate phages heavily influenced by environmental exposures. The future development of microbiome-based interventions, therapeutics, and manipulation, will require a greater understanding of the human microbiome and the virome.}, }
@article {pmid34735597, year = {2022}, author = {Regel, A and Föll, D and Kriegel, MA}, title = {[Still's syndrome-similarities and differences between the juvenile and adult forms].}, journal = {Zeitschrift fur Rheumatologie}, volume = {81}, number = {1}, pages = {22-27}, pmid = {34735597}, issn = {1435-1250}, support = {R01 AI118855/AI/NIAID NIH HHS/United States ; }, mesh = {Adult ; *Arthritis, Juvenile/diagnosis ; Child ; Cytokines ; Humans ; Joints ; *Macrophage Activation Syndrome/diagnosis/therapy ; *Still's Disease, Adult-Onset/diagnosis/therapy ; }, abstract = {Still's syndrome includes systemic juvenile idiopathic arthritis (sJIA) and the adult form of Still's disease (adult-onset Still's disease, AOSD). Except for age, there are many similarities between sJIA and AOSD. A biphasic disease model is currently put forth. At disease onset, autoinflammation predominates, which is caused by dysregulation of the innate immune system. Later on, the disease can progress to a chronic-articular form, which is predominantly mediated by the adaptive immune system and is consequently due to autoimmunity. The "window-of-opportunity" hypothesis is based on this biphasic model and supports the assumption that an early, targeted therapy with cytokine blockade can prevent disease progression to chronic destructive arthritis. Macrophage activation syndrome (MAS) is a serious complication of the so-called cytokine storm during the systemic phase of the disease. Clinically, there are many similarities between sJIA and AOSD. Recurrent fever, a fleeting, salmon-colored rash, and arthralgia/arthritis are common signs and symptoms of both sJIA and AOSD. The few differences are mainly related to the therapies and their side effects in children versus adults. In addition, the contribution of genetics to pathogenesis is more pronounced in sJIA compared to AOSD, but there are also smooth transitions in this respect and both diseases are heavily influenced by exogenous factors such as microbial triggers. Future research aspects could include additional investigation of these triggers such as viruses, bacteria, or dysbiosis of the human microbiome.}, }
@article {pmid34731631, year = {2021}, author = {Lam, KN and Spanogiannopoulos, P and Soto-Perez, P and Alexander, M and Nalley, MJ and Bisanz, JE and Nayak, RR and Weakley, AM and Yu, FB and Turnbaugh, PJ}, title = {Phage-delivered CRISPR-Cas9 for strain-specific depletion and genomic deletions in the gut microbiome.}, journal = {Cell reports}, volume = {37}, number = {5}, pages = {109930}, pmid = {34731631}, issn = {2211-1247}, support = {T32 GM007810/GM/NIGMS NIH HHS/United States ; T32 AI060537/AI/NIAID NIH HHS/United States ; R01 AT011117/AT/NCCIH NIH HHS/United States ; K08 AR073930/AR/NIAMS NIH HHS/United States ; //CIHR/Canada ; P30 DK098722/DK/NIDDK NIH HHS/United States ; R01 HL122593/HL/NHLBI NIH HHS/United States ; F32 AI147456/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Bacteriophage M13/*genetics ; CRISPR-Associated Protein 9/*genetics/metabolism ; *CRISPR-Cas Systems ; *Chromosome Deletion ; *Chromosomes, Bacterial ; *Clustered Regularly Interspaced Short Palindromic Repeats ; Escherichia coli/*genetics/growth &amp; development ; Feces/microbiology ; Female ; *Gastrointestinal Microbiome ; *Gene Editing ; Gene Expression Regulation, Bacterial ; Mice, Inbred BALB C ; Mice, Transgenic ; Proof of Concept Study ; Mice ; }, abstract = {Mechanistic insights into the role of the human microbiome in the predisposition to and treatment of disease are limited by the lack of methods to precisely add or remove microbial strains or genes from complex communities. Here, we demonstrate that engineered bacteriophage M13 can be used to deliver DNA to Escherichia coli within the mouse gastrointestinal (GI) tract. Delivery of a programmable exogenous CRISPR-Cas9 system enables the strain-specific depletion of fluorescently marked isogenic strains during competitive colonization and genomic deletions that encompass the target gene in mice colonized with a single strain. Multiple mechanisms allow E. coli to escape targeting, including loss of the CRISPR array or even the entire CRISPR-Cas9 system. These results provide a robust and experimentally tractable platform for microbiome editing, a foundation for the refinement of this approach to increase targeting efficiency, and a proof of concept for the extension to other phage-bacterial pairs of interest.}, }
@article {pmid34731146, year = {2021}, author = {Maslennikov, R and Svistunov, A and Ivashkin, V and Ufimtseva, A and Poluektova, E and Efremova, I and Ulyanin, A and Okhlobystin, A and Kardasheva, S and Kurbatova, A and Levshina, A and Grigoriadis, D and Magomedov, S and Dzhakhaya, N and Shifrin, O and Zharkova, M and Yuryeva, E and Kokina, N and Shirtladze, M and Kiseleva, O}, title = {Early viral versus late antibiotic-associated diarrhea in novel coronavirus infection.}, journal = {Medicine}, volume = {100}, number = {41}, pages = {e27528}, pmid = {34731146}, issn = {1536-5964}, mesh = {Aged ; Anti-Bacterial Agents/*adverse effects ; COVID-19/*epidemiology ; Diarrhea/*chemically induced/classification/epidemiology/*virology ; Humans ; Length of Stay ; Middle Aged ; Pandemics ; Retrospective Studies ; Risk Factors ; SARS-CoV-2 ; }, abstract = {Diarrhea is one of the manifestations of the novel coronavirus disease (COVID-19), but it also develops as a complication of massive antibiotic therapy in this disease. This study aimed to compare these types of diarrhea.We included patients with COVID-19 in a cohort study and excluded patients with chronic diarrhea, laxative use, and those who died during the first day of hospitalization.There were 89 (9.3%), 161 (16.7%), and 731 (75.7%) patients with early viral, late antibiotic-associated, and without diarrhea, respectively. Late diarrhea lasted longer (6 [4-10] vs 5 [3-7] days, P < .001) and was more severe. Clostridioides difficile was found in 70.5% of tested patients with late diarrhea and in none with early diarrhea. Presence of late diarrhea was associated with an increased risk of death after 20 days of disease (P = .009; hazard ratio = 4.7). Patients with late diarrhea had a longer hospital stay and total disease duration, and a higher proportion of these patients required intensive care unit admission. Oral amoxicillin/clavulanate (odds ratio [OR] = 2.23), oral clarithromycin (OR = 3.79), and glucocorticoids (OR = 4.41) use was a risk factor for the development of late diarrhea, while ceftriaxone use (OR = 0.35) had a protective effect. Before the development of late diarrhea, decrease in C-reactive protein levels and increase in lymphocyte count stopped but the white blood cell and neutrophil count increased. An increase in neutrophils by >0.6 × 109 cells/L predicted the development of late diarrhea in the coming days (sensitivity 82.0%, specificity 70.8%, area under the curve = 0.791 [0.710-0.872]).Diarrhea in COVID-19 is heterogeneous, and different types of diarrhea require different management.}, }
@article {pmid34718406, year = {2022}, author = {Liu, T and Xu, P and Du, Y and Lu, H and Zhao, H and Wang, T}, title = {MZINBVA: variational approximation for multilevel zero-inflated negative-binomial models for association analysis in microbiome surveys.}, journal = {Briefings in bioinformatics}, volume = {23}, number = {1}, pages = {}, doi = {10.1093/bib/bbab443}, pmid = {34718406}, issn = {1477-4054}, mesh = {Computer Simulation ; Humans ; *Microbiota ; Models, Statistical ; Research Design ; }, abstract = {As our understanding of the microbiome has expanded, so has the recognition of its critical role in human health and disease, thereby emphasizing the importance of testing whether microbes are associated with environmental factors or clinical outcomes. However, many of the fundamental challenges that concern microbiome surveys arise from statistical and experimental design issues, such as the sparse and overdispersed nature of microbiome count data and the complex correlation structure among samples. For example, in the human microbiome project (HMP) dataset, the repeated observations across time points (level 1) are nested within body sites (level 2), which are further nested within subjects (level 3). Therefore, there is a great need for the development of specialized and sophisticated statistical tests. In this paper, we propose multilevel zero-inflated negative-binomial models for association analysis in microbiome surveys. We develop a variational approximation method for maximum likelihood estimation and inference. It uses optimization, rather than sampling, to approximate the log-likelihood and compute parameter estimates, provides a robust estimate of the covariance of parameter estimates and constructs a Wald-type test statistic for association testing. We evaluate and demonstrate the performance of our method using extensive simulation studies and an application to the HMP dataset. We have developed an R package MZINBVA to implement the proposed method, which is available from the GitHub repository https://github.com/liudoubletian/MZINBVA.}, }
@article {pmid34715771, year = {2021}, author = {Geerlings, SY and Ouwerkerk, JP and Koehorst, JJ and Ritari, J and Aalvink, S and Stecher, B and Schaap, PJ and Paulin, L and de Vos, WM and Belzer, C}, title = {Genomic convergence between Akkermansia muciniphila in different mammalian hosts.}, journal = {BMC microbiology}, volume = {21}, number = {1}, pages = {298}, pmid = {34715771}, issn = {1471-2180}, mesh = {Akkermansia/classification/genetics/isolation &amp; purification/metabolism ; Animals ; Feces/microbiology ; Gastrointestinal Tract/microbiology ; Genetic Variation ; Genome, Bacterial/*genetics ; Genomics ; Humans ; Mammals/classification/*microbiology ; Mice ; Mucins/metabolism ; Phylogeny ; RNA, Ribosomal, 16S/genetics ; Verrucomicrobia/classification/genetics/isolation &amp; purification ; }, abstract = {BACKGROUND: Akkermansia muciniphila is a member of the human gut microbiota where it resides in the mucus layer and uses mucin as the sole carbon, nitrogen and energy source. A. muciniphila is the only representative of the Verrucomicrobia phylum in the human gut. However, A. muciniphila 16S rRNA gene sequences have also been found in the intestines of many vertebrates.<br><br>RESULTS: We detected A. muciniphila-like bacteria in the intestines of animals belonging to 15 out of 16 mammalian orders. In addition, other species belonging to the Verrucomicrobia phylum were detected in fecal samples. We isolated 10 new A. muciniphila strains from the feces of chimpanzee, siamang, mouse, pig, reindeer, horse and elephant. The physiology and genome of these strains were highly similar in comparison to the type strain A. muciniphila Muc[T]. Overall, the genomes of the new strains showed high average nucleotide identity (93.9 to 99.7%). In these genomes, we detected considerable conservation of at least 75 of the 78 mucin degradation genes that were previously detected in the genome of the type strain Muc[T].<br><br>CONCLUSIONS: The low genomic divergence observed in the new strains may indicate that A. muciniphila favors mucosal colonization independent of the differences in hosts. In addition, the conserved mucus degradation capability points towards a similar beneficial role of the new strains in regulating host metabolic health.}, }
@article {pmid34715674, year = {2021}, author = {Han, S and Ellberg, CC and Olomu, IN and Vyas, AK}, title = {Gestational microbiome: metabolic perturbations and developmental programming.}, journal = {Reproduction (Cambridge, England)}, volume = {162}, number = {6}, pages = {R85-R98}, doi = {10.1530/REP-21-0241}, pmid = {34715674}, issn = {1741-7899}, mesh = {*Diabetes Mellitus, Type 2 ; *Diabetes, Gestational/metabolism ; Female ; Humans ; *Microbiota ; Obesity/metabolism ; Pregnancy ; *Prenatal Exposure Delayed Effects/metabolism ; }, abstract = {A growing body of research suggests that alterations to the human microbiome are associated with disease states, including obesity and diabetes. During pregnancy, these disease states are associated with maternal microbial dysbiosis. This review discusses the current literature regarding the typical maternal and offspring microbiome as well as alterations to the microbiome in the context of obesity, type 2 diabetes mellitus, and gestational diabetes mellitus. Furthermore, this review outlines the proposed mechanisms linking associations between the maternal microbiome in the aforementioned disease states and offspring microbiome. Additionally, this review highlights associations between alterations in offspring microbiome and postnatal health outcomes.}, }
@article {pmid34704787, year = {2021}, author = {Stubbendieck, RM and Zelasko, SE and Safdar, N and Currie, CR}, title = {Biogeography of Bacterial Communities and Specialized Metabolism in Human Aerodigestive Tract Microbiomes.}, journal = {Microbiology spectrum}, volume = {9}, number = {2}, pages = {e0166921}, pmid = {34704787}, issn = {2165-0497}, support = {TL1 TR002375/TR/NCATS NIH HHS/United States ; T15 LM007359/LM/NLM NIH HHS/United States ; T32 GM140935/GM/NIGMS NIH HHS/United States ; U01 AI125053/AI/NIAID NIH HHS/United States ; U19 AI142720/AI/NIAID NIH HHS/United States ; }, mesh = {Bacteria/classification/genetics/*isolation &amp; purification/*metabolism ; Bacterial Proteins/genetics/metabolism ; Biosynthetic Pathways ; Cheek/microbiology ; *Gastrointestinal Microbiome ; Gastrointestinal Tract/*microbiology ; Genome, Bacterial ; Humans ; Microbiota ; Mouth/microbiology ; Nasal Cavity/microbiology ; Phylogeny ; }, abstract = {The aerodigestive tract (ADT) is the primary portal through which pathogens and other invading microbes enter the body. As the direct interface with the environment, we hypothesize that the ADT microbiota possess biosynthetic gene clusters (BGCs) for antibiotics and other specialized metabolites to compete with both endogenous and exogenous microbes. From 1,214 bacterial genomes, representing 136 genera and 387 species that colonize the ADT, we identified 3,895 BGCs. To determine the distribution of BGCs and bacteria in different ADT sites, we aligned 1,424 metagenomes, from nine different ADT sites, onto the predicted BGCs. We show that alpha diversity varies across the ADT and that each site is associated with distinct bacterial communities and BGCs. We identify specific BGC families enriched in the buccal mucosa, external naris, gingiva, and tongue dorsum despite these sites harboring closely related bacteria. We reveal BGC enrichment patterns indicative of the ecology at each site. For instance, aryl polyene and resorcinol BGCs are enriched in the gingiva and tongue, which are colonized by many anaerobes. In addition, we find that streptococci colonizing the tongue and cheek possess different ribosomally synthesized and posttranslationally modified peptide BGCs. Finally, we highlight bacterial genera with BGCs but are underexplored for specialized metabolism and demonstrate the bioactivity of Actinomyces against other bacteria, including human pathogens. Together, our results demonstrate that specialized metabolism in the ADT is extensive and that by exploring these microbiomes further, we will better understand the ecology and biogeography of this system and identify new bioactive natural products. IMPORTANCE Bacteria produce specialized metabolites to compete with other microbes. Though the biological activities of many specialized metabolites have been determined, our understanding of their ecology is limited, particularly within the human microbiome. As the aerodigestive tract (ADT) faces the external environment, bacteria colonizing this tract must compete both among themselves and with invading microbes, including human pathogens. We analyzed the genomes of ADT bacteria to identify biosynthetic gene clusters (BGCs) for specialized metabolites. We found that the majority of ADT BGCs are uncharacterized and the metabolites they encode are unknown. We mapped the distribution of BGCs across the ADT and determined that each site is associated with its own distinct bacterial community and BGCs. By further characterizing these BGCs, we will inform our understanding of ecology and biogeography across the ADT, and we may uncover new specialized metabolites, including antibiotics.}, }
@article {pmid34699641, year = {2021}, author = {Swanson, BA and Carson, MD and Hathaway-Schrader, JD and Warner, AJ and Kirkpatrick, JE and Corker, A and Alekseyenko, AV and Westwater, C and Aguirre, JI and Novince, CM}, title = {Antimicrobial-induced oral dysbiosis exacerbates naturally occurring alveolar bone loss.}, journal = {FASEB journal : official publication of the Federation of American Societies for Experimental Biology}, volume = {35}, number = {11}, pages = {e22015}, pmid = {34699641}, issn = {1530-6860}, support = {P30 DK123704/DK/NIDDK NIH HHS/United States ; T32 GM132055/GM/NIGMS NIH HHS/United States ; K08 DE025337/DE/NIDCR NIH HHS/United States ; R25 GM113278/GM/NIGMS NIH HHS/United States ; P20 GM130457/GM/NIGMS NIH HHS/United States ; R21 TR002513/TR/NCATS NIH HHS/United States ; R01 DE023783/DE/NIDCR NIH HHS/United States ; T32 DE017551/DE/NIDCR NIH HHS/United States ; P20 GM121342/GM/NIGMS NIH HHS/United States ; R01 LM012517/LM/NLM NIH HHS/United States ; R01 DE029637/DE/NIDCR NIH HHS/United States ; }, mesh = {Alveolar Bone Loss/*microbiology ; Animals ; Anti-Bacterial Agents/*adverse effects ; Dysbiosis/*microbiology ; Female ; Gastrointestinal Microbiome/*drug effects ; *Host Microbial Interactions ; Male ; Mice ; Mice, Inbred C57BL ; }, abstract = {Periodontitis-mediated alveolar bone loss is caused by dysbiotic shifts in the commensal oral microbiota that upregulate proinflammatory osteoimmune responses. The study purpose was to determine whether antimicrobial-induced disruption of the commensal microbiota has deleterious effects on alveolar bone. We administered an antibiotic cocktail, minocycline, or vehicle-control to sex-matched C57BL/6T mice from age 6- to 12 weeks. Antibiotic cocktail and minocycline had catabolic effects on alveolar bone in specific-pathogen-free (SPF) mice. We then administered minocycline or vehicle-control to male mice reared under SPF and germ-free conditions, and we subjected minocycline-treated SPF mice to chlorhexidine oral antiseptic rinses. Alveolar bone loss was greater in vehicle-treated SPF versus germ-free mice, demonstrating that the commensal microbiota drives naturally occurring alveolar bone loss. Minocycline- versus vehicle-treated germ-free mice had similar alveolar bone loss outcomes, implying that antimicrobial-driven alveolar bone loss is microbiota dependent. Minocycline induced phylum-level shifts in the oral bacteriome and exacerbated naturally occurring alveolar bone loss in SPF mice. Chlorhexidine further disrupted the oral bacteriome and worsened alveolar bone loss in minocycline-treated SPF mice, validating that antimicrobial-induced oral dysbiosis has deleterious effects on alveolar bone. Minocycline enhanced osteoclast size and interface with alveolar bone in SPF mice. Neutrophils and plasmacytoid dendritic cells were upregulated in cervical lymph nodes of minocycline-treated SPF mice. Paralleling the upregulated proinflammatory innate immune cells, minocycline therapy increased TH 1 and TH 17 cells that have known pro-osteoclastic actions in the alveolar bone. This report reveals that antimicrobial perturbation of the commensal microbiota induces a proinflammatory oral dysbiotic state that exacerbates naturally occurring alveolar bone loss.}, }
@article {pmid34697034, year = {2022}, author = {Koopen, A and Witjes, J and Wortelboer, K and Majait, S and Prodan, A and Levin, E and Herrema, H and Winkelmeijer, M and Aalvink, S and Bergman, JJGHM and Havik, S and Hartmann, B and Levels, H and Bergh, PO and van Son, J and Balvers, M and Bastos, DM and Stroes, E and Groen, AK and Henricsson, M and Kemper, EM and Holst, J and Strauch, CM and Hazen, SL and Bäckhed, F and De Vos, WM and Nieuwdorp, M and Rampanelli, E}, title = {Duodenal Anaerobutyricum soehngenii infusion stimulates GLP-1 production, ameliorates glycaemic control and beneficially shapes the duodenal transcriptome in metabolic syndrome subjects: a randomised double-blind placebo-controlled cross-over study.}, journal = {Gut}, volume = {71}, number = {8}, pages = {1577-1587}, pmid = {34697034}, issn = {1468-3288}, mesh = {Blood Glucose/metabolism ; Blood Glucose Self-Monitoring ; Clostridiales ; Cross-Over Studies ; *Diabetes Mellitus, Type 2/drug therapy ; Double-Blind Method ; Glucagon-Like Peptide 1/metabolism ; Glycemic Control ; Humans ; Insulin/metabolism ; *Insulin Resistance ; Male ; *Metabolic Syndrome/genetics ; Transcriptome ; }, abstract = {OBJECTIVE: Although gut dysbiosis is increasingly recognised as a pathophysiological component of metabolic syndrome (MetS), the role and mode of action of specific gut microbes in metabolic health remain elusive. Previously, we identified the commensal butyrogenic Anaerobutyricum soehngenii to be associated with improved insulin sensitivity in subjects with MetS. In this proof-of-concept study, we investigated the potential therapeutic effects of A. soehngenii L2-7 on systemic metabolic responses and duodenal transcriptome profiles in individuals with MetS.<br><br>DESIGN: In this randomised double-blind placebo-controlled cross-over study, 12 male subjects with MetS received duodenal infusions of A. soehngenii/ placebo and underwent duodenal biopsies, mixed meal tests (6&#x2009;hours postinfusion) and 24-hour continuous glucose monitoring.<br><br>RESULTS: A. soehngenii treatment provoked a markedly increased postprandial excursion of the insulinotropic hormone glucagon-like peptide 1 (GLP-1) and an elevation of plasma secondary bile acids, which were positively associated with GLP-1 levels. Moreover, A. soehngenii treatment robustly shaped the duodenal expression of 73 genes, with the highest fold induction in the expression of regenerating islet-protein 1B (REG1B)-encoding gene. Strikingly, duodenal REG1B expression positively correlated with GLP-1 levels and negatively correlated with peripheral glucose variability, which was significantly diminished in the 24 hours following A. soehngenii intake. Mechanistically, Reg1B expression is induced upon sensing butyrate or bacterial peptidoglycan. Importantly, A. soehngenii duodenal administration was safe and well tolerated.<br><br>CONCLUSIONS: A single dose of A. soehngenii improves peripheral glycaemic control within 24 hours; it specifically stimulates intestinal GLP-1 production and REG1B expression. Further studies are needed to delineate the specific pathways involved in REG1B induction and function in insulin sensitivity.<br><br>TRIAL REGISTRATION NUMBER: NTR-NL6630.}, }
@article {pmid34696318, year = {2021}, author = {Tuomala, H and Verkola, M and Meller, A and Van der Auwera, J and Patpatia, S and Järvinen, A and Skurnik, M and Heikinheimo, A and Kiljunen, S}, title = {Phage Treatment Trial to Eradicate LA-MRSA from Healthy Carrier Pigs.}, journal = {Viruses}, volume = {13}, number = {10}, pages = {}, pmid = {34696318}, issn = {1999-4915}, mesh = {Animals ; Carrier State/microbiology/*veterinary ; Farms ; Livestock/microbiology ; Methicillin-Resistant Staphylococcus aureus/*physiology ; Nasal Cavity/microbiology ; Phage Therapy/*methods/*veterinary ; Staphylococcal Infections/*therapy/*veterinary ; Swine ; Swine Diseases/microbiology/*therapy ; }, abstract = {The increase of livestock-associated methicillin-resistant Staphylococcus aureus (LA-MRSA) causes a threat to human health. LA-MRSA can be transmitted from animals to animal caretakers, which may further spread MRSA to communities and health care facilities. The objective of this work was to study the efficacy of phage treatment in the eradication of LA-MRSA from healthy carrier pigs. A total of 19 MRSA -positive weanling pigs were assigned to a test (n = 10) and a control group (n = 9). A phage cocktail containing three Staphylococcus phages, or a control buffer was administered to the nares and skin of the pigs three times every two days, after which the phage and MRSA levels in nasal and skin swab samples were monitored for a three-week period. The sensitivity of the strains isolated during the follow-up period to the phage cocktail and each phage individually was analyzed and the pig sera were tested for antibodies against the phages used in the cocktail. The phage treatment did not cause any side effects to the pigs. Phages were found in the skin and nasal samples on the days following the phage applications, but there was no reduction in the MRSA levels in the sampled animals. Phage-resistant strains or phage-specific antibodies were not detected during the experiment. The MRSA load in these healthy carrier animals was only 10-100 CFU/swab or nasal sample, which was likely below the replication threshold of phages. The effectiveness of phage treatment to eradicate MRSA from the pigs could thus not be (reliably) determined.}, }
@article {pmid34696185, year = {2021}, author = {Mintoff, D and Borg, I and Pace, NP}, title = {The Clinical Relevance of the Microbiome in Hidradenitis Suppurativa: A Systematic Review.}, journal = {Vaccines}, volume = {9}, number = {10}, pages = {}, pmid = {34696185}, issn = {2076-393X}, abstract = {Hidradenitis suppurativa is a chronic disease of the pilosebaceous unit. The name of the condition is a testament to the presumed relationship between the disease and the microbiome. The pathophysiology of hidradenitis suppurativa is, however, complex and believed to be the product of a multifactorial interplay between the interfollicular epithelium, pilosebaceous unit, microbiome, as well as genetic and environmental factors. In this review we assimilate the existing literature regarding the role played by the human microbiome in HS in various contexts of the disease, including the pathophysiologic, therapeutic, and potentially, diagnostic as well prognostic. In conclusion, the role played by the microbiome in HS is extensive and relevant and can have bench-to-bedside applications.}, }
@article {pmid34693388, year = {2021}, author = {Baunwall, SMD and Terveer, EM and Dahlerup, JF and Erikstrup, C and Arkkila, P and Vehreschild, MJ and Ianiro, G and Gasbarrini, A and Sokol, H and Kump, PK and Satokari, R and De Looze, D and Vermeire, S and Nakov, R and Brezina, J and Helms, M and Kjeldsen, J and Rode, AA and Kousgaard, SJ and Alric, L and Trang-Poisson, C and Scanzi, J and Link, A and Stallmach, A and Kupcinskas, J and Johnsen, PH and Garborg, K and Rodríguez, ES and Serrander, L and Brummer, RJ and Galpérine, KT and Goldenberg, SD and Mullish, BH and Williams, HR and Iqbal, TH and Ponsioen, C and Kuijper, EJ and Cammarota, G and Keller, JJ and Hvas, CL}, title = {The use of Faecal Microbiota Transplantation (FMT) in Europe: A Europe-wide survey.}, journal = {The Lancet regional health. Europe}, volume = {9}, number = {}, pages = {100181}, pmid = {34693388}, issn = {2666-7762}, abstract = {BACKGROUND: Faecal microbiota transplantation (FMT) is an emerging treatment modality, but its current clinical use and organisation are unknown. We aimed to describe the clinical use, conduct, and potential for FMT in Europe.<br><br>METHODS: We invited all hospital-based FMT centres within the European Council member states to answer a web-based questionnaire covering their clinical activities, organisation, and regulation of FMT in 2019. Responders were identified from trials registered at clinicaltrials.gov and from the United European Gastroenterology (UEG) working group for stool banking and FMT.<br><br>FINDINGS: In 2019, 31 FMT centres from 17 countries reported a total of 1,874 (median 25, quartile 10-64) FMT procedures; 1,077 (57%) with Clostridioides difficile infection (CDI) as indication, 791 (42%) with experimental indications, and 6 (0&#x2022;3%) unaccounted for. Adjusted to population size, 0&#x2022;257 per 100,000 population received FMT for CDI and 0&#x2022;189 per 100,000 population for experimental indications. With estimated 12,400 (6,100-28,500) annual cases of multiple, recurrent CDI and indication for FMT in Europe, the current European FMT activity covers approximately 10% of the patients with indication. The participating centres demonstrated high safety standards and adherence to international consensus guidelines. Formal or informal regulation from health authorities was present at 21 (68%) centres.<br><br>INTERPRETATION: FMT is a widespread routine treatment for multiple, recurrent CDI and an experimental treatment. Embedded within hospital settings, FMT centres operate with high standards across Europe to provide safe FMT. A significant gap in FMT coverage suggests the need to raise clinical awareness and increase the FMT activity in Europe by at least 10-fold to meet the true, indicated need.<br><br>FUNDING: NordForsk under the Nordic Council and Innovation Fund Denmark (j.no. 8056-00006B).}, }
@article {pmid34692558, year = {2021}, author = {Li, RJ and Jie, ZY and Feng, Q and Fang, RL and Li, F and Gao, Y and Xia, HH and Zhong, HZ and Tong, B and Madsen, L and Zhang, JH and Liu, CL and Xu, ZG and Wang, J and Yang, HM and Xu, X and Hou, Y and Brix, S and Kristiansen, K and Yu, XL and Jia, HJ and He, KL}, title = {Network of Interactions Between Gut Microbiome, Host Biomarkers, and Urine Metabolome in Carotid Atherosclerosis.}, journal = {Frontiers in cellular and infection microbiology}, volume = {11}, number = {}, pages = {708088}, pmid = {34692558}, issn = {2235-2988}, mesh = {Biomarkers ; *Carotid Artery Diseases ; Clostridiales ; *Gastrointestinal Microbiome ; Humans ; Metabolome ; Metabolomics ; }, abstract = {Comprehensive analyses of multi-omics data may provide insights into interactions between different biological layers concerning distinct clinical features. We integrated data on the gut microbiota, blood parameters and urine metabolites of treatment-naive individuals presenting a wide range of metabolic disease phenotypes to delineate clinically meaningful associations. Trans-omics correlation networks revealed that candidate gut microbial biomarkers and urine metabolite feature were covaried with distinct clinical phenotypes. Integration of the gut microbiome, the urine metabolome and the phenome revealed that variations in one of these three systems correlated with changes in the other two. In a specific note about clinical parameters of liver function, we identified Eubacteriumeligens, Faecalibacteriumprausnitzii and Ruminococcuslactaris to be associated with a healthy liver function, whereas Clostridium bolteae, Tyzzerellanexills, Ruminococcusgnavus, Blautiahansenii, and Atopobiumparvulum were associated with blood biomarkers for liver diseases. Variations in these microbiota features paralleled changes in specific urine metabolites. Network modeling yielded two core clusters including one large gut microbe-urine metabolite close-knit cluster and one triangular cluster composed of a gut microbe-blood-urine network, demonstrating close inter-system crosstalk especially between the gut microbiome and the urine metabolome. Distinct clinical phenotypes are manifested in both the gut microbiome and the urine metabolome, and inter-domain connectivity takes the form of high-dimensional networks. Such networks may further our understanding of complex biological systems, and may provide a basis for identifying biomarkers for diseases. Deciphering the complexity of human physiology and disease requires a holistic and trans-omics approach integrating multi-layer data sets, including the gut microbiome and profiles of biological fluids. By studying the gut microbiome on carotid atherosclerosis, we identified microbial features associated with clinical parameters, and we observed that groups of urine metabolites correlated with groups of clinical parameters. Combining the three data sets, we revealed correlations of entities across the three systems, suggesting that physiological changes are reflected in each of the omics. Our findings provided insights into the interactive network between the gut microbiome, blood clinical parameters and the urine metabolome concerning physiological variations, and showed the promise of trans-omics study for biomarker discovery.}, }
@article {pmid34691000, year = {2021}, author = {Mancabelli, L and Milani, C and Anzalone, R and Alessandri, G and Lugli, GA and Tarracchini, C and Fontana, F and Turroni, F and Ventura, M}, title = {Free DNA and Metagenomics Analyses: Evaluation of Free DNA Inactivation Protocols for Shotgun Metagenomics Analysis of Human Biological Matrices.}, journal = {Frontiers in microbiology}, volume = {12}, number = {}, pages = {749373}, pmid = {34691000}, issn = {1664-302X}, abstract = {Culture-independent approaches now represent the gold standard for the investigation of both environmental and host-associated complex microbial communities. Nevertheless, despite the great advantages offered by these novel methodologies based on the use of next-generation DNA sequencing approaches, a number of bias sources have been identified. Among the latter, free DNA contained in biological matrices is one of the main sources of inaccuracy in reconstructing the resident microbial population of viable cells. For this reason, the photoreactive DNA-binding dye propidium monoazide (PMAxx[™]) has been developed by improving standard PMA. This compound binds and inactivates free DNA, thus preventing its amplification and sequencing. While the performances of PMA have been previously investigated, the efficiency with PMAxx[™] has been tested mainly for amplicon-based profiling approaches on a limited number of biological matrices. In this study, we validated the performance of PMAxx[™] for shotgun metagenomics approaches employing various human-associated matrices. Notably, results revealed that the effectiveness of PMAxx[™] in inactivating free DNA of prokaryotes and eukaryotes tends to vary significantly based on the biological matrices analyzed.}, }
@article {pmid34683389, year = {2021}, author = {Parkin, K and Christophersen, CT and Verhasselt, V and Cooper, MN and Martino, D}, title = {Risk Factors for Gut Dysbiosis in Early Life.}, journal = {Microorganisms}, volume = {9}, number = {10}, pages = {}, pmid = {34683389}, issn = {2076-2607}, abstract = {Dysbiosis refers to a reduction in microbial diversity, combined with a loss of beneficial taxa, and an increase in pathogenic microorganisms. Dysbiosis of the intestinal microbiota can have a substantial effect on the nervous and immune systems, contributing to the onset of several inflammatory diseases. Epidemiological studies provided insight in how changes in the living environment have contributed to an overall loss of diversity and key taxa in the gut microbiome, coinciding with increased reports of atopy and allergic diseases. The gut microbiome begins development at birth, with major transition periods occurring around the commencement of breastfeeding, and the introduction of solid foods. As such, the development of the gut microbiome remains highly plastic and easily influenced by environmental factors until around three years of age. Developing a diverse and rich gut microbiome during this sensitive period is crucial to setting up a stable gut microbiome into adulthood and to prevent gut dysbiosis. Currently, the delivery route, antibiotic exposure, and diet are the best studied drivers of gut microbiome development, as well as risk factors of gut dysbiosis during infancy. This review focuses on recent evidence regarding key environmental factors that contribute to promoting gut dysbiosis.}, }
@article {pmid34682761, year = {2021}, author = {Dinis-Oliveira, RJ}, title = {The Auto-Brewery Syndrome: A Perfect Metabolic "Storm" with Clinical and Forensic Implications.}, journal = {Journal of clinical medicine}, volume = {10}, number = {20}, pages = {}, pmid = {34682761}, issn = {2077-0383}, abstract = {Auto-brewery syndrome (ABS) is a rare, unstudied, unknown, and underreported phenomenon in modern medicine. Patients with this syndrome become inebriated and may suffer the medical and social implications of alcoholism, including arrest for inebriated driving. The pathophysiology of ABS is reportedly due to a fungal type dysbiosis of the gut that ferments some carbohydrates into ethanol and may mimic a food allergy or intolerance. This syndrome should be considered in patients with chronic obstruction or hypomotility presenting with elevated breath and blood alcohol concentrations, especially after a high carbohydrate intake. A glucose challenge test should be performed as the confirmatory test. Treatment typically includes antifungal drugs combined with changes in lifestyle and nutrition. Additional studies are particularly needed on the human microbiome to shed light on how imbalances of commensal bacteria in the gut allow yeast to colonize on a pathological level.}, }
@article {pmid34677583, year = {2022}, author = {Pärnänen, KMM and Hultman, J and Markkanen, M and Satokari, R and Rautava, S and Lamendella, R and Wright, J and McLimans, CJ and Kelleher, SL and Virta, MP}, title = {Early-life formula feeding is associated with infant gut microbiota alterations and an increased antibiotic resistance load.}, journal = {The American journal of clinical nutrition}, volume = {115}, number = {2}, pages = {407-421}, pmid = {34677583}, issn = {1938-3207}, mesh = {Bacterial Proteins/*metabolism ; Cross-Sectional Studies ; Drug Resistance, Microbial/*genetics ; Feces/microbiology ; Female ; Gastrointestinal Microbiome/*genetics ; Humans ; Infant Formula/*microbiology ; *Infant Nutritional Physiological Phenomena ; Infant, Newborn ; Infant, Premature ; Linear Models ; Male ; }, abstract = {BACKGROUND: Infants are at a high risk of acquiring fatal infections, and their treatment relies on functioning antibiotics. Antibiotic resistance genes (ARGs) are present in high numbers in antibiotic-naive infants' gut microbiomes, and infant mortality caused by resistant infections is high. The role of antibiotics in shaping the infant resistome has been studied, but there is limited knowledge on other factors that affect the antibiotic resistance burden of the infant gut.<br><br>OBJECTIVES: Our objectives were to determine the impact of early exposure to formula on the ARG load in neonates and infants born either preterm or full term. Our hypotheses were that diet causes a selective pressure that influences the microbial community of the infant gut, and formula exposure would increase the abundance of taxa that carry ARGs.<br><br>METHODS: Cross-sectionally sampled gut metagenomes of 46 neonates were used to build a generalized linear model to determine the impact of diet on ARG loads in neonates. The model was cross-validated using neonate metagenomes gathered from public databases using our custom statistical pipeline for cross-validation.<br><br>RESULTS: Formula-fed neonates had higher relative abundances of opportunistic pathogens such as Staphylococcus aureus, Staphylococcus epidermidis, Klebsiella pneumoniae, Klebsiella oxytoca, and Clostridioides difficile. The relative abundance of ARGs carried by gut bacteria was 69% higher in the formula-receiving group (fold change, 1.69; 95% CI: 1.12-2.55; P&#xa0;=&#xa0;0.013; n&#xa0;=&#xa0;180) compared to exclusively human milk-fed infants. The formula-fed infants also had significantly less typical infant bacteria, such as Bifidobacteria, that have potential health benefits.<br><br>CONCLUSIONS: The novel finding that formula exposure is correlated with a higher neonatal ARG burden lays the foundation that clinicians should consider feeding mode in addition to antibiotic use during the first months of life to minimize the proliferation of antibiotic-resistant gut bacteria in infants.}, }
@article {pmid34671696, year = {2021}, author = {Zhao, Y and Jaber, V and Lukiw, WJ}, title = {Gastrointestinal Tract Microbiome-Derived Pro-inflammatory Neurotoxins in Alzheimer's Disease.}, journal = {Journal of aging science}, volume = {9}, number = {Suppl 5}, pages = {}, pmid = {34671696}, issn = {2329-8847}, support = {R01 EY006311/EY/NEI NIH HHS/United States ; R01 AG018031/AG/NIA NIH HHS/United States ; P50 AG016573/AG/NIA NIH HHS/United States ; R01 AG038834/AG/NIA NIH HHS/United States ; P30 GM103340/GM/NIGMS NIH HHS/United States ; }, abstract = {The microbiome contained within the human gastrointestinal (GI)-tract constitutes a highly complex, dynamic and interactive internal prokaryotic ecosystem that possesses a staggering diversity, speciation and complexity. This repository of microbes comprises the largest interactive source and highest density of microbes anywhere in nature, collectively constituting the largest 'diffuse organ system' in the human body. Through the extracellular fluid (ECF), cerebrospinal fluid (CSF), lymphatic and glymphatic circulation, endocrine, systemic and neurovascular circulation and/or central and peripheral nervous systems (CNS, PNS) microbiome-derived signaling strongly impacts the health, well-being and vitality of the human host. Recent data from the Human Microbiome Initiative (HMI) and the Unified Human Gastrointestinal Genome (UHGG) consortium have classified over [~]200 thousand diverse, non-redundant prokaryotic genomes in the human GI-tract microbiome involving about [~]5 thousand different GI-tract microbes that all together encode almost [~]200 million different protein sequences. While the largest proportion of different microbiome-derived proteins, lipoproteins and nucleic acids provide essential microorganism-specific gene products necessary to support microbial structure, function and viability, many of these same components are also shed from the outer cell wall of different Gram-negative bacterial species into surrounding biofluids which eventually enter the systemic circulation. Several of these microbial-derived secreted molecular species represent some of the most pro-inflammatory and noxious neurotoxins known. These neurotoxins disrupt cell-cell adhesion and easily translocate across aged or damaged plasma membranes and into the systemic circulation, brain, and CNS and PNS compartments. For example, microbial lipoprotein glycoconjugates such as Gram-negative bacteria-derived lipopolysaccharide (LPS), bacterial amyloids and more recently small non-coding RNA (sncRNA) microbial-derived neurotoxins have been found by many independent research groups to reside within the brain cells and CNS tissues of aged patients affected with Alzheimer's disease (AD). This 'Commentary' will highlight the most recent findings on these microbial-derived secreted toxins, their neurotropic properties and the potential contribution of these neurotoxic and pro-inflammatory microbial exudates to age-related inflammatory neurodegeneration, with specific reference to the human GI-tract abundant Gram-negative anaerobe Bacteroides fragilis and to AD wherever possible.}, }
@article {pmid34671642, year = {2021}, author = {Conta, G and Del Chierico, F and Reddel, S and Marini, F and Sciubba, F and Capuani, G and Tomassini, A and Di Cocco, ME and Laforgia, N and Baldassarre, ME and Putignani, L and Miccheli, A}, title = {Longitudinal Multi-Omics Study of a Mother-Infant Dyad from Breastfeeding to Weaning: An Individualized Approach to Understand the Interactions Among Diet, Fecal Metabolome and Microbiota Composition.}, journal = {Frontiers in molecular biosciences}, volume = {8}, number = {}, pages = {688440}, pmid = {34671642}, issn = {2296-889X}, abstract = {The development of the human gut microbiota is characterized by a dynamic sequence of events from birth to adulthood, which make the gut microbiota unique for everyone. Its composition and metabolism may play a critical role in the intestinal homeostasis and health. We propose a study on a single mother-infant dyad to follow the dynamics of an infant fecal microbiota and metabolome changes in relation to breast milk composition during the lactation period and evaluate the changes induced by introduction of complementary food during the weaning period. Nuclear Magnetic Resonance (NMR)-based metabolomics was performed on breast milk and, together with 16S RNA targeted-metagenomics analysis, also on infant stool samples of a mother-infant dyad collected over a period running from the exclusive breastfeeding diet to weaning. Breast milk samples and neonatal stool samples were collected from the 4th to the 10th month of life. Both specimens were collected from day 103 to day 175, while from day 219-268 only stool samples were examined. An exploratory and a predictive analysis were carried out by means of Common component and specific weight analysis and multi-block partial least squares discriminant analysis, respectively. Stools collected during breastfeeding and during a mixed fruit/breastfeeding diet were characterized by high levels of fucosyl-oligosaccharides and glycolysis intermediates, including succinate and formate. The transition to a semi-solid food diet was characterized by several changes in fecal parameters: increase in short-chain fatty acids (SCFAs) levels, including acetate, propionate and butyrate, dissapearance of HMOs and the shift in the community composition, mainly occurring within the Firmicutes phylum. The variations in the fecal metabolome reflected the infant's diet transition, while the composition of the microbiota followed a more complex and still unstable behavior.}, }
@article {pmid34670249, year = {2021}, author = {Li, S and Su, B and He, QS and Wu, H and Zhang, T}, title = {Alterations in the oral microbiome in HIV infection: causes, effects and potential interventions.}, journal = {Chinese medical journal}, volume = {134}, number = {23}, pages = {2788-2798}, pmid = {34670249}, issn = {2542-5641}, mesh = {Dysbiosis ; *Gastrointestinal Microbiome ; *HIV Infections/drug therapy ; Humans ; *Microbiota ; Mouth ; }, abstract = {A massive depletion of CD4+ T lymphocytes has been described in early and acute human immunodeficiency virus (HIV) infection, leading to an imbalance between the human microbiome and immune responses. In recent years, a growing interest in the alterations in gut microbiota in HIV infection has led to many studies; however, only few studies have been conducted to explore the importance of oral microbiome in HIV-infected individuals. Evidence has indicated the dysbiosis of oral microbiota in people living with HIV (PLWH). Potential mechanisms might be related to the immunodeficiency in the oral cavity of HIV-infected individuals, including changes in secretory components such as reduced levels of enzymes and proteins in saliva and altered cellular components involved in the reduction and dysfunction of innate and adaptive immune cells. As a result, disrupted oral immunity in HIV-infected individuals leads to an imbalance between the oral microbiome and local immune responses, which may contribute to the development of HIV-related diseases and HIV-associated non-acquired immunodeficiency syndrome comorbidities. Although the introduction of antiretroviral therapy (ART) has led to a significant decrease in occurrence of the opportunistic oral infections in HIV-infected individuals, the dysbiosis in oral microbiome persists. Furthermore, several studies with the aim to investigate the ability of probiotics to regulate the dysbiosis of oral microbiota in HIV-infected individuals are ongoing. However, the effects of ART and probiotics on oral microbiome in HIV-infected individuals remain unclear. In this article, we review the composition of the oral microbiome in healthy and HIV-infected individuals and the possible effect of oral microbiome on HIV-associated oral diseases. We also discuss how ART and probiotics influence the oral microbiome in HIV infection. We believe that a deeper understanding of composition and function of the oral microbiome is critical for the development of effective preventive and therapeutic strategies for HIV infection.}, }
@article {pmid34669983, year = {2022}, author = {Karimova, M and Moyes, D and Ide, M and Setterfield, JF}, title = {The human microbiome in immunobullous disorders and lichen planus.}, journal = {Clinical and experimental dermatology}, volume = {47}, number = {3}, pages = {522-528}, doi = {10.1111/ced.14987}, pmid = {34669983}, issn = {1365-2230}, mesh = {Humans ; Immunosenescence ; Lichen Planus/*immunology/*microbiology ; *Microbiota ; Molecular Mimicry ; Mouth/microbiology ; Mouth Diseases/immunology/microbiology ; Skin Diseases, Vesiculobullous/*immunology/*microbiology ; }, abstract = {For several decades, there has been a significant growth in the incidence of autoimmune diseases. Studies indicate that genetic factors may not be the only trigger for disease development and that dysbiosis of the microbiome may be another mechanism involved in the pathogenesis of autoimmune diseases. The role of the microbiome in the development of common skin disorders such as psoriasis, atopic dermatitis, acne and rosacea is increasingly well understood. However, few studies have focused on lichen planus and the rare acquired immunobullous diseases, both mucocutaneous groups of disorders linked to skin, oral and gut microbiomes. This review provides an insight into the current understanding of how the microbiome may contribute to the development of autoimmunity and to the maintenance and exacerbation of acquired immunobullous and lichenoid diseases. These mechanisms may have implications for future preventive and therapeutic approaches.}, }
@article {pmid34662348, year = {2021}, author = {Earle, SG and Lobanovska, M and Lavender, H and Tang, C and Exley, RM and Ramos-Sevillano, E and Browning, DF and Kostiou, V and Harrison, OB and Bratcher, HB and Varani, G and Tang, CM and Wilson, DJ and Maiden, MCJ}, title = {Genome-wide association studies reveal the role of polymorphisms affecting factor H binding protein expression in host invasion by Neisseria meningitidis.}, journal = {PLoS pathogens}, volume = {17}, number = {10}, pages = {e1009992}, pmid = {34662348}, issn = {1553-7374}, support = {/WT_/Wellcome Trust/United Kingdom ; 102908/Z/13/Z/WT_/Wellcome Trust/United Kingdom ; R35 GM126942/GM/NIGMS NIH HHS/United States ; 087622/Z/08/Z/WT_/Wellcome Trust/United Kingdom ; 218205/Z/19/Z/WT_/Wellcome Trust/United Kingdom ; 102908/Z/13/Z/WT_/Wellcome Trust/United Kingdom ; 101237/Z/13/B/WT_/Wellcome Trust/United Kingdom ; 203141/Z/16/Z/WT_/Wellcome Trust/United Kingdom ; /DH_/Department of Health/United Kingdom ; R35 GM126942/GM/NIGMS NIH HHS/United States ; }, mesh = {Antigens, Bacterial/*genetics ; Bacterial Proteins/*genetics ; Genome-Wide Association Study ; Humans ; Meningococcal Infections/*genetics ; Neisseria meningitidis/*genetics/*pathogenicity ; Polymorphism, Single Nucleotide ; }, abstract = {Many invasive bacterial diseases are caused by organisms that are ordinarily harmless components of the human microbiome. Effective interventions against these microbes require an understanding of the processes whereby symbiotic or commensal relationships transition into pathology. Here, we describe bacterial genome-wide association studies (GWAS) of Neisseria meningitidis, a common commensal of the human respiratory tract that is nevertheless a leading cause of meningitis and sepsis. An initial GWAS discovered bacterial genetic variants, including single nucleotide polymorphisms (SNPs), associated with invasive meningococcal disease (IMD) versus carriage in several loci across the meningococcal genome, encoding antigens and other extracellular components, confirming the polygenic nature of the invasive phenotype. In particular, there was a significant peak of association around the fHbp locus, encoding factor H binding protein (fHbp), which promotes bacterial immune evasion of human complement by recruiting complement factor H (CFH) to the meningococcal surface. The association around fHbp with IMD was confirmed by a validation GWAS, and we found that the SNPs identified in the validation affected the 5' region of fHbp mRNA, altering secondary RNA structures, thereby increasing fHbp expression and enhancing bacterial escape from complement-mediated killing. This finding is consistent with the known link between complement deficiencies and CFH variation with human susceptibility to IMD. These observations demonstrate the importance of human and bacterial genetic variation across the fHbp:CFH interface in determining IMD susceptibility, the transition from carriage to disease.}, }
@article {pmid34656848, year = {2021}, author = {Tan-Torres, AL and Brooks, JP and Singh, B and Seashols-Williams, S}, title = {Machine learning clustering and classification of human microbiome source body sites.}, journal = {Forensic science international}, volume = {328}, number = {}, pages = {111008}, doi = {10.1016/j.forsciint.2021.111008}, pmid = {34656848}, issn = {1872-6283}, mesh = {Algorithms ; Cluster Analysis ; Humans ; Machine Learning ; Metagenomics ; *Microbiota ; }, abstract = {Distinct microbial signatures associated with specific human body sites can play a role in the identification of biological materials recovered from the crime scene, but at present, methods that have capability to predict origin of biological materials based on such signatures are limited. Metagenomic sequencing and machine learning (ML) offer a promising enhancement to current identification protocols. We use ML for forensic source body site identification using shotgun metagenomic sequenced data to verify the presence of microbiomic signatures capable of discriminating between source body sites and then show that accurate prediction is possible. The consistency between cluster membership and actual source body site (purity) exceeded 99% at the genus taxonomy using off-the-shelf ML clustering algorithms. Similar results were obtained at the family level. Accurate predictions were observed for genus, family, and order taxonomies, as well as with a core set of 51 genera. The accurate outcomes from our replicable process should encourage forensic scientists to seriously consider integrating ML predictors into their source body site identification protocols.}, }
@article {pmid34650058, year = {2021}, author = {Ji, X and Sun, T and Xie, S and Qian, H and Song, L and Wang, L and Liu, H and Feng, Q}, title = {Upregulation of CPNE7 in mesenchymal stromal cells promotes oral squamous cell carcinoma metastasis through the NF-κB pathway.}, journal = {Cell death discovery}, volume = {7}, number = {1}, pages = {294}, pmid = {34650058}, issn = {2058-7716}, abstract = {A remarkable shift in Mesenchymal stromal cells (MSCs) plays an important role in cancer metastasis, but the molecular mechanism is still unclear. CPNE7, a calcium-dependent phospholipid-binding protein, mediates signal transduction and metastasis in many tumours. Here, we demonstrated that MSCs derived from OSCC (OSCC-MSCs) promoted the metastasis of OSCC cells by transwell assay and animal models through epithelial to mesenchymal transition (EMT) (p < 0.05). RNA-sequencing, ELISA, neutralizing antibody and CXCR2 inhibitor assay confirmed that CXCL8 secreted by OSCC-MSCs was associated with the upregulated expression of CPNE7 by immunohistochemical and western blotting (p < 0.05). This is mechanistically linked to the activation of CPNE7 to NF-κB pathway-induced metastasis, including phosphorylated p65 and IκBa. CPNE7 silencing inhibited metastatic abilities and the expression of CXCL8, phosphorylated p65, IκBa, and p65 nuclear translocation by western blotting and immunofluorescence, while CPNE7 overexpression markedly promoted these events (p < 0.05). We also identified that Nucleolin could be bind CPNE7 and IκBa by co-immunoprecipitation. Together, our results suggest that upregulation of CPNE7 in MSCs interacted with surface receptor -Nucleolin and then combined with IκBa to promoted phosphorylated IκBa and p65 nuclear translocation to active NF-κB pathway, and then regulates CXCL8 secretion to promote the metastasis of OSCC cells. Therefore, CPNE7 in MSCs could be promising therapeutic targets in OSCC.}, }
@article {pmid34647264, year = {2021}, author = {Elton, S}, title = {Intimate ecosystems: the microbiome and the ecological determinants of health.}, journal = {Canadian journal of public health = Revue canadienne de sante publique}, volume = {112}, number = {6}, pages = {1004-1007}, pmid = {34647264}, issn = {1920-7476}, mesh = {Ecosystem ; *Health Equity ; Humans ; *Microbiota ; }, abstract = {The ecological determinants of health make explicit the ways in which human health and well-being depend on the biosphere and its systems. Water, oxygen, and food are listed along with soil systems, water systems, material for shelter, energy, the ozone layer and a stable climate. Research in the sciences is uncovering the critical role that the earth microbiome, including the human microbiome, plays in human health. The relationship between commensal microbiota and the systems of the human body, as well as the ways in which these systems are interdependent with other ecosystems such as food systems, invites revisiting the ecological determinants of health. In this commentary, I argue that microbiota, including the human microbiome, should be considered ecological determinants of health. Such a characterization would recognize the importance of the microbiome to human health. It would also frame this as a public health issue and raise questions about health equity, including who benefits from the knowledge produced through biomedical research.}, }
@article {pmid34646255, year = {2021}, author = {Glowacki, RWP and Engelhart, MJ and Ahern, PP}, title = {Controlled Complexity: Optimized Systems to Study the Role of the Gut Microbiome in Host Physiology.}, journal = {Frontiers in microbiology}, volume = {12}, number = {}, pages = {735562}, pmid = {34646255}, issn = {1664-302X}, abstract = {The profound impact of the gut microbiome on host health has led to a revolution in biomedical research, motivating researchers from disparate fields to define the specific molecular mechanisms that mediate host-beneficial effects. The advent of genomic technologies allied to the use of model microbiomes in gnotobiotic mouse models has transformed our understanding of intestinal microbial ecology and the impact of the microbiome on the host. However, despite incredible advances, our understanding of the host-microbiome dialogue that shapes host physiology is still in its infancy. Progress has been limited by challenges associated with developing model systems that are both tractable enough to provide key mechanistic insights while also reflecting the enormous complexity of the gut ecosystem. Simplified model microbiomes have facilitated detailed interrogation of transcriptional and metabolic functions of the microbiome but do not recapitulate the interactions seen in complex communities. Conversely, intact complex communities from mice or humans provide a more physiologically relevant community type, but can limit our ability to uncover high-resolution insights into microbiome function. Moreover, complex microbiomes from lab-derived mice or humans often do not readily imprint human-like phenotypes. Therefore, improved model microbiomes that are highly defined and tractable, but that more accurately recapitulate human microbiome-induced phenotypic variation are required to improve understanding of fundamental processes governing host-microbiome mutualism. This improved understanding will enhance the translational relevance of studies that address how the microbiome promotes host health and influences disease states. Microbial exposures in wild mice, both symbiotic and infectious in nature, have recently been established to more readily recapitulate human-like phenotypes. The development of synthetic model communities from such "wild mice" therefore represents an attractive strategy to overcome the limitations of current approaches. Advances in microbial culturing approaches that allow for the generation of large and diverse libraries of isolates, coupled to ever more affordable large-scale genomic sequencing, mean that we are now ideally positioned to develop such systems. Furthermore, the development of sophisticated in vitro systems is allowing for detailed insights into host-microbiome interactions to be obtained. Here we discuss the need to leverage such approaches and highlight key challenges that remain to be addressed.}, }
@article {pmid34643888, year = {2023}, author = {Ivashkin, V and Fomin, V and Moiseev, S and Brovko, M and Maslennikov, R and Ulyanin, A and Sholomova, V and Vasilyeva, M and Trush, E and Shifrin, O and Poluektova, E}, title = {Efficacy of a Probiotic Consisting of Lacticaseibacillus rhamnosus PDV 1705, Bifidobacterium bifidum PDV 0903, Bifidobacterium longum subsp. infantis PDV 1911, and Bifidobacterium longum subsp. longum PDV 2301 in the Treatment of Hospitalized Patients with COVID-19: a Randomized Controlled Trial.}, journal = {Probiotics and antimicrobial proteins}, volume = {15}, number = {3}, pages = {460-468}, pmid = {34643888}, issn = {1867-1314}, mesh = {Humans ; Aged ; *Bifidobacterium bifidum ; *Lacticaseibacillus rhamnosus ; Lacticaseibacillus ; *COVID-19/therapy ; *Probiotics/therapeutic use ; Diarrhea/prevention &amp; control ; Bifidobacterium longum subspecies infantis ; Anti-Bacterial Agents/therapeutic use ; }, abstract = {The treatment of coronavirus disease (COVID-19) and COVID-19-associated diarrhea remains challenging. This study aimed to evaluate the efficacy of a multi-strain probiotic in the treatment of COVID-19. This was a randomized, controlled, single-center, open-label trial (NCT04854941). Inpatients with confirmed COVID-19 and pneumonia were randomly assigned to a group that received a multi-strain probiotic (PRO group) or to the control group (CON group). There were 99 and 101 patients in the PRO and CON groups, respectively. No significant differences in mortality, total duration of disease and hospital stay, incidence of intensive care unit admission, need for mechanical ventilation or oxygen support, liver injury development, and changes in inflammatory biomarker levels were observed between the PRO and CON groups among all included patients as well as among subgroups delineated based on age younger or older than 65 years, and subgroups with chronic cardiovascular diseases and diabetes. Diarrhea on admission was observed in 11.5% of patients; it resolved earlier in the PRO group than in the CON group (2 [1-4] vs. 4 [3-6] days; p = 0.049). Hospital-acquired diarrhea developed less frequently in the PRO group than in the CON group among patients who received a single antibiotic (0% vs. 12.5%; p = 0.023) unlike among those who received > 1 antibiotic (10.5% vs. 13.3%; p = 0.696). The studied probiotic had no significant effect on mortality and changes in most biomarkers in COVID-19. However, it was effective in treating diarrhea associated with COVID-19 and in preventing hospital-acquired diarrhea in patients who received a single antibiotic.}, }
@article {pmid34642755, year = {2022}, author = {Vanhaecke, T and Bretin, O and Poirel, M and Tap, J}, title = {Drinking Water Source and Intake Are Associated with Distinct Gut Microbiota Signatures in US and UK Populations.}, journal = {The Journal of nutrition}, volume = {152}, number = {1}, pages = {171-182}, pmid = {34642755}, issn = {1541-6100}, mesh = {*Drinking Water ; Feces ; Female ; *Gastrointestinal Microbiome ; Humans ; Male ; Middle Aged ; Phylogeny ; RNA, Ribosomal, 16S ; United Kingdom ; }, abstract = {BACKGROUND: The microbiome of the digestive tract exerts fundamental roles in host physiology. Extrinsic factors including lifestyle and diet are widely recognized as key drivers of gut and oral microbiome compositions. Although drinking water is among the food items consumed in the largest amount, little is known about its potential impact on the microbiome.<br><br>OBJECTIVES: We explored the associations of plain drinking water source and intake with gut and oral microbiota compositions in a population-based cohort.<br><br>METHODS: Microbiota, health, lifestyle, and food intake data were extracted from the American Gut Project public database. Associations of drinking water source (bottled, tap, filtered, or well water) and intake with global microbiota composition were evaluated using linear and logistic models adjusted for anthropometric, diet, and lifestyle factors in 3413 and 3794 individuals, respectively (fecal samples; 56% female, median [IQR] age: 48 [36-59] y; median [IQR] BMI: 23.3 [20.9-26.3] kg/m2), and in 283 and 309 individuals, respectively (oral samples).<br><br>RESULTS: Drinking water source ranked among the key contributing factors explaining the gut microbiota variation, accounting for 13% [Faith's phylogenetic diversity (Faith's PD)] and 47% (Bray-Curtis dissimilarity) of the age effect size. Drinking water source was associated with differences in gut microbiota signatures, as revealed by &#x3b2; diversity analyses (P&#xa0;<&#xa0;0.05; Bray-Curtis dissimilarity, weighted UniFrac distance). Subjects drinking mostly well water had higher fecal &#x3b1; diversity (P&#xa0;<&#xa0;0.05; Faith's PD, observed amplicon sequence variants), higher Dorea, and lower Bacteroides, Odoribacter, and Streptococcus than the other groups. Low water drinkers also exhibited gut microbiota differences compared with high water drinkers (P&#xa0;<&#xa0;0.05; Bray-Curtis dissimilarity, unweighted UniFrac distance) and a higher abundance of Campylobacter. No associations were found between oral microbiota composition and drinking water consumption.<br><br>CONCLUSIONS: Our results indicate that drinking water may be an important factor in shaping the human gut microbiome and that integrating drinking water source and intake as covariates in future microbiome analyses is warranted.}, }
@article {pmid34641955, year = {2021}, author = {Arikawa, K and Ide, K and Kogawa, M and Saeki, T and Yoda, T and Endoh, T and Matsuhashi, A and Takeyama, H and Hosokawa, M}, title = {Recovery of strain-resolved genomes from human microbiome through an integration framework of single-cell genomics and metagenomics.}, journal = {Microbiome}, volume = {9}, number = {1}, pages = {202}, pmid = {34641955}, issn = {2049-2618}, mesh = {Genome, Microbial ; Humans ; Metagenome ; *Metagenomics ; *Microbiota/genetics ; Phylogeny ; }, abstract = {BACKGROUND: Obtaining high-quality (HQ) reference genomes from microbial communities is crucial for understanding the phylogeny and function of uncultured microbes in complex microbial ecosystems. Despite improvements in bioinformatic approaches to generate curated metagenome-assembled genomes (MAGs), existing metagenome binners obtain population consensus genomes but they are nowhere comparable to genomes sequenced from isolates in terms of strain level resolution. Here, we present a framework for the integration of single-cell genomics and metagenomics, referred to as single-cell (sc) metagenomics, to reconstruct strain-resolved genomes from microbial communities at once.<br><br>RESULTS: Our sc-metagenomics integration framework, termed SMAGLinker, uses single-cell amplified genomes (SAGs) generated using microfluidic technology as binning guides and integrates them with metagenome-assembled genomes (MAGs) to recover improved draft genomes. We compared sc-metagenomics with the metagenomics-alone approach using conventional metagenome binners. The sc-metagenomics approach showed precise contig binning and higher recovery rates (>97%) of rRNA and plasmids than conventional metagenomics in genome reconstruction from the cell mock community. In human microbiota samples, sc-metagenomics recovered the largest number of genomes with a total of 103 gut microbial genomes (21 HQ, with 65 showing >90% completeness) and 45 skin microbial genomes (10 HQ, with 40 showing >90% completeness), respectively. Conventional metagenomics recovered one Staphylococcus hominis genome, whereas sc-metagenomics recovered two S. hominis genomes from identical skin microbiota sample. Single-cell sequencing revealed that these S. hominis genomes were derived from two distinct strains harboring specifically different plasmids. We found that all conventional S. hominis MAGs had a substantial lack or excess of genome sequences and contamination from other Staphylococcus species (S. epidermidis).<br><br>CONCLUSIONS: SMAGLinker enabled us to obtain strain-resolved genomes in the mock community and human microbiota samples by assigning metagenomic sequences correctly and covering both highly conserved genes such as rRNA genes and unique extrachromosomal elements, including plasmids. SMAGLinker will provide HQ genomes that are difficult to obtain using metagenomics alone and will facilitate the understanding of microbial ecosystems by elucidating detailed metabolic pathways and horizontal gene transfer networks. SMAGLinker is available at https://github.com/kojiari/smaglinker . Video abstract.}, }
@article {pmid34641521, year = {2021}, author = {Dohnálek, J and Dušková, J and Tishchenko, G and Kolenko, P and Skálová, T and Novák, P and Fejfarová, K and Šimůnek, J}, title = {Chitinase Chit62J4 Essential for Chitin Processing by Human Microbiome Bacterium Clostridium paraputrificum J4.}, journal = {Molecules (Basel, Switzerland)}, volume = {26}, number = {19}, pages = {}, pmid = {34641521}, issn = {1420-3049}, support = {LM2015043, LM2018127//Ministry of Education, Youth and Sports of the Czech Republic/ ; CZ.1.05/1.1.00/02.0109//European Regional Development Fund/ ; CZ.02.1.01/0.0/0.0/15_003/0000447//European Regional Development Fund/ ; 86652036//Czech Academy of Sciences/ ; }, mesh = {Bacterial Proteins/genetics/*metabolism ; Catalytic Domain ; Chitin/*metabolism ; Chitinases/chemistry/genetics/*metabolism ; Clostridium/growth &amp; development/isolation &amp; purification/*metabolism ; Gastrointestinal Microbiome ; Humans ; Hydrogen-Ion Concentration ; Recombinant Proteins/genetics/metabolism ; }, abstract = {Commensal bacterium Clostridium paraputrificum J4 produces several extracellular chitinolytic enzymes including a 62 kDa chitinase Chit62J4 active toward 4-nitrophenyl N,N'-diacetyl-β-d-chitobioside (pNGG). We characterized the crude enzyme from bacterial culture fluid, recombinant enzyme rChit62J4, and its catalytic domain rChit62J4cat. This major chitinase, securing nutrition of the bacterium in the human intestinal tract when supplied with chitin, has a pH optimum of 5.5 and processes pNGG with Km = 0.24 mM and kcat = 30.0 s[-1]. Sequence comparison of the amino acid sequence of Chit62J4, determined during bacterial genome sequencing, characterizes the enzyme as a family 18 glycosyl hydrolase with a four-domain structure. The catalytic domain has the typical TIM barrel structure and the accessory domains-2x Fn3/Big3 and a carbohydrate binding module-that likely supports enzyme activity on chitin fibers. The catalytic domain is highly homologous to a single-domain chitinase of Bacillus cereus NCTU2. However, the catalytic profiles significantly differ between the two enzymes despite almost identical catalytic sites. The shift of pI and pH optimum of the commensal enzyme toward acidic values compared to the soil bacterium is the likely environmental adaptation that provides C. paraputrificum J4 a competitive advantage over other commensal bacteria.}, }
@article {pmid34639020, year = {2021}, author = {Suojalehto, H and Ndika, J and Lindström, I and Airaksinen, L and Karvala, K and Kauppi, P and Lauerma, A and Toppila-Salmi, S and Karisola, P and Alenius, H}, title = {Transcriptomic Profiling of Adult-Onset Asthma Related to Damp and Moldy Buildings and Idiopathic Environmental Intolerance.}, journal = {International journal of molecular sciences}, volume = {22}, number = {19}, pages = {}, pmid = {34639020}, issn = {1422-0067}, support = {114350//The Finnish Work Environment Fund/ ; }, mesh = {Adult ; *Air Pollution, Indoor ; Asthma/*etiology ; Blood Cells/immunology/metabolism ; Case-Control Studies ; Cytokines/metabolism ; *Disease Susceptibility ; Environmental Exposure/*adverse effects ; Female ; *Fungi ; *Gene Expression Profiling ; Humans ; Immunophenotyping ; Macrophages/immunology/metabolism ; Male ; Middle Aged ; Risk Factors ; *Transcriptome ; }, abstract = {A subset of adult-onset asthma patients attribute their symptoms to damp and moldy buildings. Symptoms of idiopathic environmental intolerance (IEI) may resemble asthma and these two entities overlap. We aimed to evaluate if a distinct clinical subtype of asthma related to damp and moldy buildings can be identified, to unravel its corresponding pathomechanistic gene signatures, and to investigate potential molecular similarities with IEI. Fifty female adult-onset asthma patients were categorized based on exposure to building dampness and molds during disease initiation. IEI patients (n = 17) and healthy subjects (n = 21) were also included yielding 88 study subjects. IEI was scored with the Quick Environmental Exposure and Sensitivity Inventory (QEESI) questionnaire. Inflammation was evaluated by blood cell type profiling and cytokine measurements. Disease mechanisms were investigated via gene set variation analysis of RNA from nasal biopsies and peripheral blood mononuclear cells. Nasal biopsy gene expression and plasma cytokine profiles suggested airway and systemic inflammation in asthma without exposure to dampness (AND). Similar evidence of inflammation was absent in patients with dampness-and-mold-related asthma (AAD). Gene expression signatures revealed a greater degree of similarity between IEI and dampness-related asthma than between IEI patients and asthma not associated to dampness and mold. Blood cell transcriptome of IEI subjects showed strong suppression of immune cell activation, migration, and movement. QEESI scores correlated to blood cell gene expression of all study subjects. Transcriptomic analysis revealed clear pathomechanisms for AND but not AAD patients. Furthermore, we found a distinct molecular pathological profile in nasal and blood immune cells of IEI subjects, including several differentially expressed genes that were also identified in AAD samples, suggesting IEI-type mechanisms.}, }
@article {pmid34638770, year = {2021}, author = {Georgiou, K and Marinov, B and Farooqi, AA and Gazouli, M}, title = {Gut Microbiota in Lung Cancer: Where Do We Stand?.}, journal = {International journal of molecular sciences}, volume = {22}, number = {19}, pages = {}, pmid = {34638770}, issn = {1422-0067}, mesh = {*Carcinoma, Non-Small-Cell Lung/immunology/microbiology/therapy ; Gastrointestinal Microbiome/*immunology ; Humans ; Immune Checkpoint Inhibitors/*therapeutic use ; *Lung Neoplasms/immunology/microbiology/therapy ; T-Lymphocytes, Regulatory/*immunology/pathology ; }, abstract = {The gut microbiota (GM) is considered to constitute a powerful "organ" capable of influencing the majority of the metabolic, nutritional, physiological, and immunological processes of the human body. To date, five microbial-mediated mechanisms have been revealed that either endorse or inhibit tumorigenesis. Although the gastrointestinal and respiratory tracts are distant physically, they have common embryonic origin and similarity in structure. The lung microbiota is far less understood, and it is suggested that the crosslink between the human microbiome and lung cancer is a complex, multifactorial relationship. Several pathways linking their respective microbiota have reinforced the existence of a gut-lung axis (GLA). Regarding implications of specific GM in lung cancer therapy, a few studies showed that the GM considerably affects immune checkpoint inhibitor (ICI) therapy by altering the differentiation of regulatory T cells and thus resulting in changes in immunomodulation mechanisms, as discovered by assessing drug metabolism directly and by assessing the host immune modulation response. Additionally, the GM may increase the efficacy of chemotherapeutic treatment in lung cancer. The mechanism underlying the role of the GLA in the pathogenesis and progression of lung cancer and its capability for diagnosis, manipulation, and treatment need to be further explored.}, }
@article {pmid34637779, year = {2021}, author = {Chipashvili, O and Utter, DR and Bedree, JK and Ma, Y and Schulte, F and Mascarin, G and Alayyoubi, Y and Chouhan, D and Hardt, M and Bidlack, F and Hasturk, H and He, X and McLean, JS and Bor, B}, title = {Episymbiotic Saccharibacteria suppresses gingival inflammation and bone loss in mice through host bacterial modulation.}, journal = {Cell host &amp; microbe}, volume = {29}, number = {11}, pages = {1649-1662.e7}, pmid = {34637779}, issn = {1934-6069}, support = {K99 DE027719/DE/NIDCR NIH HHS/United States ; R01 DE020102/DE/NIDCR NIH HHS/United States ; R01 DE031274/DE/NIDCR NIH HHS/United States ; R21 DE027199/DE/NIDCR NIH HHS/United States ; R00 DE027719/DE/NIDCR NIH HHS/United States ; R01 DE023810/DE/NIDCR NIH HHS/United States ; R01 DE026186/DE/NIDCR NIH HHS/United States ; R01 GM095373/GM/NIGMS NIH HHS/United States ; F31 DE026057/DE/NIDCR NIH HHS/United States ; }, mesh = {Actinobacteria/genetics/isolation &amp; purification/*pathogenicity/physiology ; Actinomyces/genetics/isolation &amp; purification/pathogenicity/physiology ; Alveolar Bone Loss/*microbiology/prevention &amp; control ; Animals ; Bacteria/classification/isolation &amp; purification/pathogenicity ; Bacterial Infections/microbiology/prevention &amp; control ; *Bacterial Physiological Phenomena ; Collagen/metabolism ; Dental Plaque/microbiology ; Down-Regulation ; Genes, Bacterial ; Gingivitis/*microbiology/prevention &amp; control ; Humans ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Microbiota ; N-Acetylneuraminic Acid/metabolism ; Periodontitis/*microbiology/prevention &amp; control ; Propionibacteriaceae/genetics/isolation &amp; purification/pathogenicity/physiology ; *Symbiosis ; Virulence ; }, abstract = {Saccharibacteria (TM7) are obligate epibionts living on the surface of their host bacteria and are strongly correlated with dysbiotic microbiomes during periodontitis and other inflammatory diseases, suggesting they are putative pathogens. However, due to the recalcitrance of TM7 cultivation, causal research to investigate their role in inflammatory diseases is lacking. Here, we isolated multiple TM7 species on their host bacteria from periodontitis patients. These TM7 species reduce inflammation and consequential bone loss by modulating host bacterial pathogenicity in a mouse ligature-induced periodontitis model. Two host bacterial functions involved in collagen binding and utilization of eukaryotic sialic acid are required for inducing bone loss and are altered by TM7 association. This TM7-mediated downregulation of host bacterial pathogenicity is shown for multiple TM7/host bacteria pairs, suggesting that, in contrast to their suspected pathogenic role, TM7 could protect mammalian hosts from inflammatory damage induced by their host bacteria.}, }
@article {pmid34636673, year = {2021}, author = {De Wolfe, TJ and Arefin, MR and Benezra, A and Rebolleda Gómez, M}, title = {Chasing Ghosts: Race, Racism, and the Future of Microbiome Research.}, journal = {mSystems}, volume = {6}, number = {5}, pages = {e0060421}, pmid = {34636673}, issn = {2379-5077}, support = {RT-2020-04-64//Michael Smith Foundation for Health Research (MSFHR)/ ; }, abstract = {In this article, we argue that a careful examination of human microbiome science's relationship with race and racism is necessary to foster equitable social and ecological relations in the field. We point to the origins and evolution of the problematic use of race in microbiome literature by demonstrating the increased usage of race both explicitly and implicitly in and beyond the human microbiome sciences. We demonstrate how these uses limit the future of rigorous and just microbiome research. We conclude with an outline of alternative actionable ways to build a more effective, antiracist microbiome science.}, }
@article {pmid34628621, year = {2021}, author = {Giraldo, PC and Sanches, JM and Sparvolli, LG and Amaral, R and Migliorini, I and Gil, CD and Taddei, CR and Witkin, SS and Discacciati, MG}, title = {Relationship between Papillomavirus vaccine, vaginal microbiome, and local cytokine response: an exploratory research.}, journal = {Brazilian journal of microbiology : [publication of the Brazilian Society for Microbiology]}, volume = {52}, number = {4}, pages = {2363-2371}, pmid = {34628621}, issn = {1678-4405}, support = {2016/08392-3//FAPESP/ ; }, mesh = {Adult ; *Bacteria/drug effects/genetics ; *Cytokines/immunology ; Female ; Human papillomavirus 16 ; Human papillomavirus 18 ; Humans ; *Microbiota/drug effects/genetics ; *Papillomavirus Infections/prevention &amp; control ; *Papillomavirus Vaccines/pharmacology ; RNA, Ribosomal, 16S/genetics ; *Vagina/microbiology ; Young Adult ; }, abstract = {INTRODUCTION: The influence of vaccination on composition of the human microbiome at distinct sites has been recognized as an essential component in the development of new vaccine strategies. The HPV vaccine is widely used to prevent cervical cancer; however, the influence of HPV vaccine on the vaginal microbiota has not been previously investigated. In his study, we performed an initial characterization of the microbiome and cytokine composition in the vagina following administration of the bivalent vaccine against HPV 16/18.<br><br>MATERIAL AND METHODS: In this exploratory study, fifteen women between 18 and 40&#xa0;years received three doses of the HPV-16/18 AS04-adjuvanted vaccine (Cervarix&#xae;). Cervicovaginal samples were collected before the first dose and 30&#xa0;days after the third dose. HPV genotyping was performed by the XGEN Flow Chip technique. The cytokines IFN-&#x3b3;, IL-2, IL-12p70, TNF-&#x3b1;, GM-CSF, IL-4, IL-5, IL-10, and IL-13 were quantitated by multiplex immunoassay. The vaginal microbiome was identified by analysis of the V3/V4 region of the bacterial 16S rRNA gene.<br><br>RESULTS: The most abundant bacterial species in the vaginal microbiome was Lactobacillus crispatus, followed by L. iners. Bacterial diversity and dominant organisms were unchanged following vaccination. Small decreases in levels of pro and anti-inflammatory cytokines were observed following HPV vaccination, but there was no association between vaginal cytokine levels and microbiome composition.<br><br>CONCLUSION: Vaginal microbiome is not altered following administration of the standard three-dose HPV-16/18 AS04-adjuvanted (Cervarix&#xae;) vaccine.}, }
@article {pmid34616771, year = {2021}, author = {Medeiros Filho, F and do Nascimento, APB and Costa, MOCE and Merigueti, TC and de Menezes, MA and Nicolás, MF and Dos Santos, MT and Carvalho-Assef, APD and da Silva, FAB}, title = {A Systematic Strategy to Find Potential Therapeutic Targets for Pseudomonas aeruginosa Using Integrated Computational Models.}, journal = {Frontiers in molecular biosciences}, volume = {8}, number = {}, pages = {728129}, pmid = {34616771}, issn = {2296-889X}, abstract = {Pseudomonas aeruginosa is an opportunistic human pathogen that has been a constant global health problem due to its ability to cause infection at different body sites and its resistance to a broad spectrum of clinically available antibiotics. The World Health Organization classified multidrug-resistant Pseudomonas aeruginosa among the top-ranked organisms that require urgent research and development of effective therapeutic options. Several approaches have been taken to achieve these goals, but they all depend on discovering potential drug targets. The large amount of data obtained from sequencing technologies has been used to create computational models of organisms, which provide a powerful tool for better understanding their biological behavior. In the present work, we applied a method to integrate transcriptome data with genome-scale metabolic networks of Pseudomonas aeruginosa. We submitted both metabolic and integrated models to dynamic simulations and compared their performance with published in vitro growth curves. In addition, we used these models to identify potential therapeutic targets and compared the results to analyze the assumption that computational models enriched with biological measurements can provide more selective and (or) specific predictions. Our results demonstrate that dynamic simulations from integrated models result in more accurate growth curves and flux distribution more coherent with biological observations. Moreover, identifying drug targets from integrated models is more selective as the predicted genes were a subset of those found in the metabolic models. Our analysis resulted in the identification of 26 non-host homologous targets. Among them, we highlighted five top-ranked genes based on lesser conservation with the human microbiome. Overall, some of the genes identified in this work have already been proposed by different approaches and (or) are already investigated as targets to antimicrobial compounds, reinforcing the benefit of using integrated models as a starting point to selecting biologically relevant therapeutic targets.}, }
@article {pmid34616291, year = {2021}, author = {Sergazy, S and Gulyayev, A and Amangeldiyeva, A and Nurgozhina, A and Nurgaziyev, M and Shulgau, Z and Chulenbayeva, L and Khassenbekova, Z and Kushugulova, A and Aljofan, M}, title = {Antiradical and Cytoprotective Properties of Allium nutans L. Honey Against CCL4-Induced Liver Damage in Rats.}, journal = {Frontiers in pharmacology}, volume = {12}, number = {}, pages = {687763}, pmid = {34616291}, issn = {1663-9812}, abstract = {The aim of this study is determine the in vitro and in vivo antiradical properties and the cytoprotective activity of Allium nutans L. honey extract. The antiradical properties of the extracts were investigated in rabbit alveolar macrophages and human foreskin fibroblast (hFFs) cells in the presence of doxorubicin, a cytotoxic substance using DPPH and ABTS assays. The cytoprotective activities were determined using 18 Wistar rats divided into three different groups, a negative control, and two other groups with experimentally induced hepatotoxicity by a single intraperitoneal injection of 50% carbon tetrachloride (CCl4) oil solution. A positive control group, received drinking water only and an experimental group that was treated with Allium nutans L. honey extracts for 7 days. In vitro treatment with Allium nutans L. honey extracts resulted in 78% reduction in radical activity in DPPH and 91.6% inhibition using the ABTS. Also, honey extracts were able to preserve 100% of cell viability in the presence of the cytotoxic, doxorubicin. Furthermore, the treatment with honey extracts resulted in a significant reduction in damage to the structure of liver tissue, as well significant reduction in the levels of ALT and AST in the experimental group compared to the control group.}, }
@article {pmid34615932, year = {2021}, author = {Morrow, JD and Castaldi, PJ and Chase, RP and Yun, JH and Lee, S and Liu, YY and Hersh, CP}, title = {Peripheral blood microbial signatures in current and former smokers.}, journal = {Scientific reports}, volume = {11}, number = {1}, pages = {19875}, pmid = {34615932}, issn = {2045-2322}, support = {R01 HL130512/HL/NHLBI NIH HHS/United States ; U01 HL089897/HL/NHLBI NIH HHS/United States ; U01 HL089856/HL/NHLBI NIH HHS/United States ; R01 HL147326/HL/NHLBI NIH HHS/United States ; R01 AI141529/AI/NIAID NIH HHS/United States ; K25 HL136846/HL/NHLBI NIH HHS/United States ; R01 HL124233/HL/NHLBI NIH HHS/United States ; K08 HL146972/HL/NHLBI NIH HHS/United States ; R01 HL125583/HL/NHLBI NIH HHS/United States ; }, mesh = {Aged ; Aged, 80 and over ; Female ; Humans ; Male ; Middle Aged ; Disease Susceptibility ; Follow-Up Studies ; Genetic Predisposition to Disease ; Host Microbial Interactions ; Host-Pathogen Interactions ; Lung/microbiology ; *Microbiota ; Pulmonary Disease, Chronic Obstructive/complications/diagnosis/etiology ; Respiratory Function Tests ; *Sepsis/diagnosis/etiology/microbiology ; *Smokers ; Smoking/adverse effects ; }, abstract = {The human microbiome has a role in the development of multiple diseases. Individual microbiome profiles are highly personalized, though many species are shared. Understanding the relationship between the human microbiome and disease may inform future individualized treatments. We hypothesize the blood microbiome signature may be a surrogate for some lung microbial characteristics. We sought associations between the blood microbiome signature and lung-relevant host factors. Based on reads not mapped to the human genome, we detected microbial nucleic acids through secondary use of peripheral blood RNA-sequencing from 2,590 current and former smokers with and without chronic obstructive pulmonary disease (COPD) from the COPDGene study. We used the Genome Analysis Toolkit (GATK) microbial pipeline PathSeq to infer microbial profiles. We tested associations between the inferred profiles and lung disease relevant phenotypes and examined links to host gene expression pathways. We replicated our analyses using a second independent set of blood RNA-seq data from 1,065 COPDGene study subjects and performed a meta-analysis across the two studies. The four phyla with highest abundance across all subjects were Proteobacteria, Actinobacteria, Firmicutes and Bacteroidetes. In our meta-analysis, we observed associations (q-value < 0.05) between Acinetobacter, Serratia, Streptococcus and Bacillus inferred abundances and Modified Medical Research Council (mMRC) dyspnea score. Current smoking status was associated (q < 0.05) with Acinetobacter, Serratia and Cutibacterium abundance. All 12 taxa investigated were associated with at least one white blood cell distribution variable. Abundance for nine of the 12 taxa was associated with sex, and seven of the 12 taxa were associated with race. Host-microbiome interaction analysis revealed clustering of genera associated with mMRC dyspnea score and smoking status, through shared links to several host pathways. This study is the first to identify a bacterial microbiome signature in the peripheral blood of current and former smokers. Understanding the relationships between systemic microbial signatures and lung-related phenotypes may inform novel interventions and aid understanding of the systemic effects of smoking.}, }
@article {pmid34612695, year = {2021}, author = {Gierse, LC and Meene, A and Schultz, D and Schwaiger, T and Schröder, C and Mücke, P and Zühlke, D and Hinzke, T and Wang, H and Methling, K and Kreikemeyer, B and Bernhardt, J and Becher, D and Mettenleiter, TC and Lalk, M and Urich, T and Riedel, K}, title = {Influenza A H1N1 Induced Disturbance of the Respiratory and Fecal Microbiome of German Landrace Pigs - a Multi-Omics Characterization.}, journal = {Microbiology spectrum}, volume = {9}, number = {2}, pages = {e0018221}, pmid = {34612695}, issn = {2165-0497}, mesh = {Animals ; Bacteria/*classification/genetics/*isolation &amp; purification ; Disease Models, Animal ; Fatty Acids, Volatile/biosynthesis ; Feces/microbiology ; Female ; Gastrointestinal Microbiome/*physiology ; Gene Expression Profiling ; Influenza A Virus, H1N1 Subtype/pathogenicity ; Male ; Orthomyxoviridae Infections/*pathology ; Proteomics ; RNA, Ribosomal, 16S/genetics ; Respiratory System/*microbiology ; Swine ; }, abstract = {Seasonal influenza outbreaks represent a large burden for the health care system as well as the economy. While the role of the microbiome has been elucidated in the context of various diseases, the impact of respiratory viral infections on the human microbiome is largely unknown. In this study, swine was used as an animal model to characterize the temporal dynamics of the respiratory and gastrointestinal microbiome in response to an influenza A virus (IAV) infection. A multi-omics approach was applied on fecal samples to identify alterations in microbiome composition and function during IAV infection. We observed significantly altered microbial richness and diversity in the gastrointestinal microbiome after IAV infection. In particular, increased abundances of Prevotellaceae were detected, while Clostridiaceae and Lachnospiraceae decreased. Moreover, our metaproteomics data indicated that the functional composition of the microbiome was heavily affected by the influenza infection. For instance, we identified decreased amounts of flagellin, correlating with reduced abundances of Lachnospiraceae and Clostridiaceae, possibly indicating involvement of a direct immune response toward flagellated Clostridia during IAV infection. Furthermore, enzymes involved in short-chain fatty acid (SCFA) synthesis were identified in higher abundances, while metabolome analyses revealed rather stable concentrations of SCFAs. In addition, 16S rRNA gene sequencing was used to characterize effects on the composition and natural development of the upper respiratory tract microbiome. Our results showed that IAV infection resulted in significant changes in the abundance of Moraxellaceae and Pasteurellaceae in the upper respiratory tract. Surprisingly, temporal development of the respiratory microbiome structure was not affected. IMPORTANCE Here, we used swine as a biomedical model to elucidate the impact of influenza A H1N1 infection on structure and function of the respiratory and gastrointestinal tract microbiome by employing a multi-omics analytical approach. To our knowledge, this is the first study to investigate the temporal development of the porcine microbiome and to provide insights into the functional capacity of the gastrointestinal microbiome during influenza A virus infection.}, }
@article {pmid34611047, year = {2022}, author = {Lv, S and Wang, Y and Zhang, W and Shang, H}, title = {Trimethylamine oxide: a potential target for heart failure therapy.}, journal = {Heart (British Cardiac Society)}, volume = {108}, number = {12}, pages = {917-922}, doi = {10.1136/heartjnl-2021-320054}, pmid = {34611047}, issn = {1468-201X}, mesh = {Cardiotonic Agents ; Carnitine/metabolism ; Choline/metabolism ; Diuretics ; *Gastrointestinal Microbiome/physiology ; *Heart Failure/drug therapy ; Humans ; Methylamines ; }, abstract = {Heart failure (HF) is a clinical syndrome in the late stage of cardiovascular disease and is associated with high prevalence, mortality and rehospitalisation rate. The pathophysiological mechanisms of HF have experienced the initial 'water-sodium retention' mode to 'abnormal hemodynamics' mode, and subsequent to 'abnormal activation of neuroendocrine' mode, which has extensively promoted the reform of HF treatment and updated the treatment concept. Since the Human Microbiome Project commencement, the study on intestinal microecology has swiftly developed, providing a new direction to reveal the occurrence of diseases and the mechanisms behind drug effects. Intestinal microecology comprises the gastrointestinal lumen, epithelial secretion, food entering the intestine, intestinal flora and metabolites. Choline and L-carnitine in the diet are metabolised to trimethylamine (TMA) by the intestinal micro-organisms, with TMA being absorbed into the blood. TMA then enters the liver through the portal vein circulation and is oxidised to trimethylamine oxide (TMAO) by the hepatic flavin-containing mono-oxygenase (FMO) family, especially FMO3. The circulating TMAO levels are associated with adverse outcomes in HF (mortality and readmission), and lower TMAO levels indicate better prognosis. As HF progresses, the concentration of TMAO in patients gradually increases. Whether the circulating TMAO level can be decreased by intervening with the intestinal microflora or relevant enzymes, thereby affecting the prognosis of patients with HF, has become a research hotspot. Therefore, based on the HF intestinal hypothesis, exploring the treatment strategy for HF targeting the TMAO metabolite of the intestinal flora may update the treatment concept in HF and improve its therapeutic effect.}, }
@article {pmid34609165, year = {2021}, author = {Boix-Amorós, A and Piras, E and Bu, K and Wallach, D and Stapylton, M and Fernández-Sesma, A and Malaspina, D and Clemente, JC}, title = {Viral Inactivation Impacts Microbiome Estimates in a Tissue-Specific Manner.}, journal = {mSystems}, volume = {6}, number = {5}, pages = {e0067421}, pmid = {34609165}, issn = {2379-5077}, support = {R01 MH110418/MH/NIMH NIH HHS/United States ; 5R01MH110418//HHS | National Institutes of Health (NIH)/ ; }, abstract = {The global emergence of novel pathogenic viruses presents an important challenge for research, as high biosafety levels are required to process samples. While inactivation of infectious agents facilitates the use of less stringent safety conditions, its effect on other biological entities of interest present in the sample is generally unknown. Here, we analyzed the effect of five inactivation methods (heat, ethanol, formaldehyde, psoralen, and TRIzol) on microbiome composition and diversity in samples collected from four different body sites (gut, nasal, oral, and skin) and compared them against untreated samples from the same tissues. We performed 16S rRNA gene sequencing and estimated abundance and diversity of bacterial taxa present in all samples. Nasal and skin samples were the most affected by inactivation, with ethanol and TRIzol inducing the largest changes in composition, and heat, formaldehyde, TRIzol, and psoralen inducing the largest changes in diversity. Oral and stool microbiomes were more robust to inactivation, with no significant changes in diversity and only moderate changes in composition. Firmicutes was the taxonomic group least affected by inactivation, while Bacteroidetes had a notable enrichment in nasal samples and moderate enrichment in fecal and oral samples. Actinobacteria were more notably depleted in fecal and skin samples, and Proteobacteria exhibited a more variable behavior depending on sample type and inactivation method. Overall, our results demonstrate that inactivation methods can alter the microbiome in a tissue-specific manner and that careful consideration should be given to the choice of method based on the sample type under study. IMPORTANCE Understanding how viral infections impact and are modulated by the microbiome is an important problem in basic research but is also of high clinical relevance under the current pandemic. To facilitate the study of interactions between microbial communities and pathogenic viruses under safe conditions, the infectious agent is generally inactivated prior to processing samples. The effect of this inactivation process in the microbiome is, however, unknown. Further, it is unclear whether biases introduced by inactivation methods are dependent on the sample type under study. Estimating the magnitude and nature of the changes induced by different methods in samples collected from various body sites thus provides important information for current and future studies that require inactivation of pathogenic agents.}, }
@article {pmid34596014, year = {2021}, author = {Kajova, M and Khawaja, T and Kangas, J and Mäkinen, H and Kantele, A}, title = {Import of multidrug-resistant bacteria from abroad through interhospital transfers, Finland, 2010-2019.}, journal = {Euro surveillance : bulletin Europeen sur les maladies transmissibles = European communicable disease bulletin}, volume = {26}, number = {39}, pages = {}, pmid = {34596014}, issn = {1560-7917}, mesh = {Anti-Bacterial Agents/pharmacology/therapeutic use ; Drug Resistance, Multiple, Bacterial ; Enterobacteriaceae ; Finland/epidemiology ; Hospitals, University ; Humans ; *Methicillin-Resistant Staphylococcus aureus/genetics ; beta-Lactamases/genetics ; }, abstract = {BackgroundWhile 20-80% of regular visitors to (sub)tropical regions become colonised by extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBL-PE), those hospitalised abroad often also carry other multidrug-resistant (MDR) bacteria on return; the rates are presumed to be highest for interhospital transfers.AimThis observational study assessed MDR bacterial colonisation among patients transferred directly from hospitals abroad to Helsinki University Hospital. We investigated predisposing factors, clinical infections and associated fatalities.MethodsData were derived from screening and from diagnostic samples collected between 2010 and 2019. Risk factors of colonisation were identified by multivariable analysis. Microbiologically verified symptomatic infections and infection-related mortality were recorded during post-transfer hospitalisation.ResultsColonisation rates proved highest for transfers from Asia (69/96; 71.9%) and lowest for those within Europe (99/524; 18.9%). Of all 698 patients, 208 (29.8%) were colonised; among those, 163 (78.4%) carried ESBL-PE, 28 (13.5%) MDR Acinetobacter species, 25 (12.0%) meticillin-resistant Staphylococcus aureus, 25 (12.0%) vancomycin-resistant Enterococcus, 14 (6.7%) carbapenemase-producing Enterobacteriaceae, and 12 (5.8%) MDR Pseudomonas aeruginosa; 46 strains tested carbapenemase gene-positive. In multivariable analysis, geographical region, intensive care unit (ICU) treatment and antibiotic use abroad proved to be risk factors for colonisation. Clinical MDR infections, two of them fatal (1.0%), were recorded for 22 of 208 (10.6%) MDR carriers.ConclusionsColonisation by MDR bacteria was common among patients transferred from foreign hospitals. Region of hospitalisation, ICU treatment and antibiotic use were identified as predisposing factors. Within 30 days after transfer, MDR colonisation manifested as clinical infection in more than 10% of the carriers.}, }
@article {pmid34594028, year = {2021}, author = {Toni, T and Alverdy, J and Gershuni, V}, title = {Re-examining chemically defined liquid diets through the lens of the microbiome.}, journal = {Nature reviews. Gastroenterology &amp; hepatology}, volume = {18}, number = {12}, pages = {903-911}, pmid = {34594028}, issn = {1759-5053}, support = {R01 GM062344/GM/NIGMS NIH HHS/United States ; }, mesh = {Critical Care/*history/methods ; Critical Illness/therapy ; Diet/adverse effects/*history/methods ; Dietary Fiber/microbiology/therapeutic use ; Food, Formulated/adverse effects/*history ; *Gastrointestinal Microbiome ; History, 20th Century ; Humans ; Malnutrition/diet therapy/history/microbiology ; Nutritional Support/*history/methods ; Parenteral Nutrition, Total/adverse effects/history/methods ; Perioperative Care/adverse effects/*history/methods ; United States ; }, abstract = {Trends in nutritional science are rapidly shifting as information regarding the value of eating unprocessed foods and its salutary effect on the human microbiome emerge. Unravelling the evolution and ecology by which humans have harboured a microbiome that participates in every facet of health and disease is daunting. Most strikingly, the host habitat has sought out naturally occurring foodstuff that can fulfil its own metabolic needs and also the needs of its microbiota, each of which remain inexorably connected to one another. With the introduction of modern medicine and complexities of critical care, came the assumption that the best way to feed a critically ill patient is by delivering fibre-free chemically defined sterile liquid foods (that is, total enteral nutrition). In this Perspective, we uncover the potential flaws in this assumption and discuss how emerging technology in microbiome sciences might inform the best method of feeding malnourished and critically ill patients.}, }
@article {pmid34589068, year = {2021}, author = {Buckel, W}, title = {Energy Conservation in Fermentations of Anaerobic Bacteria.}, journal = {Frontiers in microbiology}, volume = {12}, number = {}, pages = {703525}, pmid = {34589068}, issn = {1664-302X}, abstract = {Anaerobic bacteria ferment carbohydrates and amino acids to obtain energy for growth. Due to the absence of oxygen and other inorganic electron acceptors, the substrate of a fermentation has to serve as electron donor as well as acceptor, which results in low free energies as compared to that of aerobic oxidations. Until about 10 years ago, anaerobes were thought to exclusively use substrate level phosphorylation (SLP), by which only part of the available energy could be conserved. Therefore, anaerobes were regarded as unproductive and inefficient energy conservers. The discovery of electrochemical Na[+] gradients generated by biotin-dependent decarboxylations or by reduction of NAD[+] with ferredoxin changed this view. Reduced ferredoxin is provided by oxidative decarboxylation of 2-oxoacids and the recently discovered flavin based electron bifurcation (FBEB). In this review, the two different fermentation pathways of glutamate to ammonia, CO2, acetate, butyrate and H2 via 3-methylaspartate or via 2-hydroxyglutarate by members of the Firmicutes are discussed as prototypical examples in which all processes characteristic for fermentations occur. Though the fermentations proceed on two entirely different pathways, the maximum theoretical amount of ATP is conserved in each pathway. The occurrence of the 3-methylaspartate pathway in clostridia from soil and the 2-hydroxyglutarate pathway in the human microbiome of the large intestine is traced back to the oxygen-sensitivity of the radical enzymes. The coenzyme B12-dependent glutamate mutase in the 3-methylaspartate pathway tolerates oxygen, whereas 2-hydroxyglutaryl-CoA dehydratase is extremely oxygen-sensitive and can only survive in the gut, where the combustion of butyrate produced by the microbiome consumes the oxygen and provides a strict anaerobic environment. Examples of coenzyme B12-dependent eliminases are given, which in the gut are replaced by simpler extremely oxygen sensitive glycyl radical enzymes.}, }
@article {pmid34588993, year = {2021}, author = {Montanari, C and Parolisi, S and Borghi, E and Putignani, L and Bassanini, G and Zuvadelli, J and Bonfanti, C and Tummolo, A and Dionisi Vici, C and Biasucci, G and Burlina, A and Carbone, MT and Verduci, E}, title = {Dysbiosis, Host Metabolism, and Non-communicable Diseases: Trialogue in the Inborn Errors of Metabolism.}, journal = {Frontiers in physiology}, volume = {12}, number = {}, pages = {716520}, pmid = {34588993}, issn = {1664-042X}, abstract = {Inborn errors of metabolism (IEMs) represent a complex system model, in need of a shift of approach exploring the main factors mediating the regulation of the system, internal or external and overcoming the traditional concept of biochemical and genetic defects. In this context, among the established factors influencing the metabolic flux, i.e., diet, lifestyle, antibiotics, xenobiotics, infectious agents, also the individual gut microbiota should be considered. A healthy gut microbiota contributes in maintaining human health by providing unique metabolic functions to the human host. Many patients with IEMs are on special diets, the main treatment for these diseases. Hence, IEMs represent a good model to evaluate how specific dietary patterns, in terms of macronutrients composition and quality of nutrients, can be related to a characteristic microbiota associated with a specific clinical phenotype ("enterophenotype"). In the present review, we aim at reporting the possible links existing between dysbiosis, a condition reported in IEMs patients, and a pro-inflammatory status, through an altered "gut-liver" cross-talk network and a major oxidative stress, with a repercussion on the health status of the patient, increasing the risk of non-communicable diseases (NCDs). On this basis, more attention should be paid to the nutritional status assessment and the clinical and biochemical signs of possible onset of comorbidities, with the goal of improving the long-term wellbeing in IEMs. A balanced intestinal ecosystem has been shown to positively contribute to patient health and its perturbation may influence the clinical spectrum of individuals with IEMs. For this, reaching eubiosis through the improvement of the quality of dietary products and mixtures, the use of pre-, pro- and postbiotics, could represent both a preventive and therapeutic strategy in these complex diseases.}, }
@article {pmid34588273, year = {2021}, author = {Kussmann, M and Obermueller, M and Spettel, K and Winkler, S and Aletaha, D}, title = {In vitro evaluation of disease-modifying antirheumatic drugs against rheumatoid arthritis associated pathogens of the oral microflora.}, journal = {RMD open}, volume = {7}, number = {3}, pages = {}, pmid = {34588273}, issn = {2056-5933}, mesh = {*Antirheumatic Agents/pharmacology/therapeutic use ; *Arthritis, Rheumatoid/drug therapy ; Humans ; Methotrexate/pharmacology/therapeutic use ; *Microbiota ; Sulfasalazine/pharmacology/therapeutic use ; }, abstract = {OBJECTIVES: In the past, the human microbiome has consistently been associated with rheumatoid arthritis (RA) and disease activity. Here, we investigate the antimicrobial activity of disease-modifying antirheumatic drugs (DMARDs) against typical representatives of the oral microflora that have been associated with RA.<br><br>METHODS: DMARDs were screened for antimicrobial activity against bacteria that are associated with the pathogenesis of the disease and/or frequently isolated from the oral microflora of patients with RA. Screening was done by an agar diffusion assay and minimum inhibitory concentrations (MICs) of antimicrobial active substances were then determined by broth dilution.<br><br>RESULTS: Aurothiomalate and sulfasalazine demonstrated broad-spectrum antimicrobial activity, but with MICs ranging from 18 to >280 &#xb5;g/mL and 150 to >600 &#xb5;g/mL, respectively, only at supratherapeutic concentrations. Methotrexate showed antimicrobial activity only against Fusobacterium nucleatum and Viridans streptococci. The corresponding MICs were 3.75 to >30 &#xb5;g/mL and 0.5-15 &#xb5;g/mL, respectively, thus at least for streptococci, within the therapeutically achievable range. No other DMARD tested showed antimicrobial activity in the agar diffusion screening assay.<br><br>CONCLUSION: Methotrexate, sulfasalazine and aurothiomalate showed antimicrobial activity against a broad spectrum of RA associated pathogens of the oral microflora. While methotrexate showed relevant antimicrobial activity, and to a more limited extent aurothiomalate, sulfasalazine was active only at far supratherapeutic systemic concentrations. Nevertheless, given the highly species-dependent antimicrobial activity and the multiple ways it can affect the human microbiome, our results suggest a link between antimicrobially active antirheumatic drugs and their potential effect in the treatment of RA.}, }
@article {pmid34587184, year = {2021}, author = {Chen, X and Liu, L and Chu, Q and Sun, S and Wu, Y and Tong, Z and Fang, W and Timko, MP and Fan, L}, title = {Large-scale identification of extracellular plant miRNAs in mammals implicates their dietary intake.}, journal = {PloS one}, volume = {16}, number = {9}, pages = {e0257878}, pmid = {34587184}, issn = {1932-6203}, mesh = {Animal Feed/analysis ; Animals ; Brain Chemistry ; Carnivora/genetics ; Computational Biology/*methods ; Diet ; Female ; Herbivory/genetics ; Humans ; MicroRNAs/*genetics ; Milk, Human/chemistry ; Organ Specificity ; Plants/*genetics ; RNA, Plant/genetics ; Sample Size ; Sequence Analysis, RNA/*methods ; }, abstract = {Extracellular microRNAs (miRNAs) have been proposed to function in cross-kingdom gene regulation. Among these, plant-derived miRNAs of dietary origin have been reported to survive the harsh conditions of the human digestive system, enter the circulatory system, and regulate gene expression and metabolic function. However, definitive evidence supporting the presence of plant-derived miRNAs of dietary origin in mammals has been difficult to obtain due to limited sample sizes. We have developed a bioinformatics pipeline (ePmiRNA_finder) that provides strident miRNA classification and applied it to analyze 421 small RNA sequencing data sets from 10 types of human body fluids and tissues and comparative samples from carnivores and herbivores. A total of 35 miRNAs were identified that map to plants typically found in the human diet and these miRNAs were found in at least one human blood sample and their abundance was significantly different when compared to samples from human microbiome or cow. The plant-derived miRNA profiles were body fluid/tissue-specific and highly abundant in the brain and the breast milk samples, indicating selective absorption and/or the ability to be transported across tissue/organ barriers. Our data provide conclusive evidence for the presence of plant-derived miRNAs as a consequence of dietary intake and their cross-kingdom regulatory function within human circulating system.}, }
@article {pmid34587158, year = {2021}, author = {Mero, S and Timonen, S and Lääveri, T and Løfberg, S and Kirveskari, J and Ursing, J and Rombo, L and Kofoed, PE and Kantele, A}, title = {Prevalence of diarrhoeal pathogens among children under five years of age with and without diarrhoea in Guinea-Bissau.}, journal = {PLoS neglected tropical diseases}, volume = {15}, number = {9}, pages = {e0009709}, pmid = {34587158}, issn = {1935-2735}, mesh = {Bacteria/classification/genetics/*isolation &amp; purification ; Bacterial Infections/epidemiology/*microbiology ; Child, Preschool ; Diarrhea/epidemiology/*microbiology/*virology ; Feces/microbiology/virology ; Female ; Guinea-Bissau/epidemiology ; Humans ; Infant ; Male ; Virus Diseases/epidemiology/*virology ; Viruses/classification/genetics/*isolation &amp; purification ; }, abstract = {BACKGROUND: Childhood diarrhoea, a major cause of morbidity and mortality in low-income regions, remains scarcely studied in many countries, such as Guinea-Bissau. Stool sample drying enables later qPCR analyses of pathogens without concern about electricity shortages.<br><br>METHODS: Dried stool samples of children under five years treated at the Bandim Health Centre in Bissau, Guinea-Bissau were screened by qPCR for nine enteric bacteria, five viruses, and four parasites. The findings of children having and not having diarrhoea were compared in age groups 0-11 and 12-59 months.<br><br>RESULTS: Of the 429 children- 228 with and 201 without diarrhoea- 96.9% and 93.5% had bacterial, 62.7% and 44.3% viral, and 52.6% and 48.3% parasitic pathogen findings, respectively. Enteroaggregarive Escherichia coli (EAEC; 60.5% versus 66.7%), enteropathogenic E. coli (EPEC; 61.4% versus 62.7%), Campylobacter (53.2% versus 51.8%), and enterotoxigenic E. coli (ETEC; 54.4% versus 44.3%) were the most common bacterial pathogens. Diarrhoea was associated with enteroinvasive E. coli (EIEC)/Shigella (63.3%), ETEC (54.4%), astrovirus (75.0%), norovirus GII (72.6%) and Cryptosporidium (71.2%). The only pathogen associated with severe diarrhoea was EIEC/Shigella (p<0.001). EAEC was found more frequent among the infants, and EIEC/Shigella, Giardia duodenalis and Dientamoeba fragilis among the older children.<br><br>CONCLUSIONS: Stool pathogens proved common among all the children regardless of them having diarrhoea or not.}, }
@article {pmid34581596, year = {2021}, author = {Huus, KE and Ley, RE}, title = {Blowing Hot and Cold: Body Temperature and the Microbiome.}, journal = {mSystems}, volume = {6}, number = {5}, pages = {e0070721}, pmid = {34581596}, issn = {2379-5077}, support = {//Max Planck Society/ ; //Max Planck Society/ ; }, abstract = {The intestinal microbiome influences host health, and its responsiveness to diet and disease is increasingly well studied. However, our understanding of the factors driving microbiome variation remain limited. Temperature is a core factor that controls microbial growth, but its impact on the microbiome remains to be fully explored. Although commonly assumed to be a constant 37°C, normal body temperatures vary across the animal kingdom, while individual body temperature is affected by multiple factors, including circadian rhythm, age, environmental temperature stress, and immune activation. Changes in body temperature via hypo- and hyperthermia have been shown to influence the gut microbiota in a variety of animals, with consistent effects on community diversity and stability. It is known that temperature directly modulates the growth and virulence of gastrointestinal pathogens; however, the effect of temperature on gut commensals is not well studied. Further, body temperature can influence other host factors, such as appetite and immunity, with indirect effects on the microbiome. In this minireview, we discuss the evidence linking body temperature and the intestinal microbiome and their implications for microbiome function during hypothermia, heat stress, and fever.}, }
@article {pmid34580445, year = {2021}, author = {Aggarwala, V and Mogno, I and Li, Z and Yang, C and Britton, GJ and Chen-Liaw, A and Mitcham, J and Bongers, G and Gevers, D and Clemente, JC and Colombel, JF and Grinspan, A and Faith, J}, title = {Precise quantification of bacterial strains after fecal microbiota transplantation delineates long-term engraftment and explains outcomes.}, journal = {Nature microbiology}, volume = {6}, number = {10}, pages = {1309-1318}, pmid = {34580445}, issn = {2058-5276}, support = {R01 DK123749/DK/NIDDK NIH HHS/United States ; U24 CA224319/CA/NCI NIH HHS/United States ; U01 DK124165/DK/NIDDK NIH HHS/United States ; R01 DK112978/DK/NIDDK NIH HHS/United States ; R01 DK124133/DK/NIDDK NIH HHS/United States ; }, mesh = {Algorithms ; Bacteria/classification/genetics/*isolation &amp; purification ; Benchmarking ; Clostridioides difficile/physiology ; Clostridium Infections/microbiology/therapy ; *Fecal Microbiota Transplantation/methods ; Feces/microbiology ; Gastrointestinal Microbiome ; Humans ; Longitudinal Studies ; Metagenome/genetics ; Recurrence ; Tissue Donors ; Treatment Outcome ; }, abstract = {Fecal microbiota transplantation (FMT) has been successfully applied to treat recurrent Clostridium difficile infection in humans, but a precise method to measure which bacterial strains stably engraft in recipients and evaluate their association with clinical outcomes is lacking. We assembled a collection of >1,000 different bacterial strains that were cultured from the fecal samples of 22 FMT donors and recipients. Using our strain collection combined with metagenomic sequencing data from the same samples, we developed a statistical approach named Strainer for the detection and tracking of bacterial strains from metagenomic sequencing data. We applied Strainer to evaluate a cohort of 13 FMT longitudinal clinical interventions and detected stable engraftment of 71% of donor microbiota strains in recipients up to 5 years post-FMT. We found that 80% of recipient gut bacterial strains pre-FMT were eliminated by FMT and that post-FMT the strains present persisted up to 5 years later, together with environmentally acquired strains. Quantification of donor bacterial strain engraftment in recipients independently explained (precision 100%, recall 95%) the clinical outcomes (relapse or success) after initial and repeat FMT. We report a compendium of bacterial species and strains that consistently engraft in recipients over time that could be used in defined live biotherapeutic products as an alternative to FMT. Our analytical framework and Strainer can be applied to systematically evaluate either FMT or defined live bacterial therapeutic studies by quantification of strain engraftment in recipients.}, }
@article {pmid34572284, year = {2021}, author = {Dietert, RR}, title = {Microbiome First Medicine in Health and Safety.}, journal = {Biomedicines}, volume = {9}, number = {9}, pages = {}, pmid = {34572284}, issn = {2227-9059}, abstract = {Microbiome First Medicine is a suggested 21st century healthcare paradigm that prioritizes the entire human, the human superorganism, beginning with the microbiome. To date, much of medicine has protected and treated patients as if they were a single species. This has resulted in unintended damage to the microbiome and an epidemic of chronic disorders [e.g., noncommunicable diseases and conditions (NCDs)]. Along with NCDs came loss of colonization resistance, increased susceptibility to infectious diseases, and increasing multimorbidity and polypharmacy over the life course. To move toward sustainable healthcare, the human microbiome needs to be front and center. This paper presents microbiome-human physiology from the view of systems biology regulation. It also details the ongoing NCD epidemic including the role of existing drugs and other factors that damage the human microbiome. Examples are provided for two entryway NCDs, asthma and obesity, regarding their extensive network of comorbid NCDs. Finally, the challenges of ensuring safety for the microbiome are detailed. Under Microbiome-First Medicine and considering the importance of keystone bacteria and critical windows of development, changes in even a few microbiota-prioritized medical decisions could make a significant difference in health across the life course.}, }
@article {pmid34566921, year = {2021}, author = {Jaakkola, K and Virtanen, K and Lahti, P and Keto-Timonen, R and Lindström, M and Korkeala, H}, title = {Comparative Genome Analysis and Spore Heat Resistance Assay Reveal a New Component to Population Structure and Genome Epidemiology Within Clostridium perfringens Enterotoxin-Carrying Isolates.}, journal = {Frontiers in microbiology}, volume = {12}, number = {}, pages = {717176}, pmid = {34566921}, issn = {1664-302X}, abstract = {Clostridium perfringens causes a variety of human and animal enteric diseases including food poisoning, antibiotic-associated diarrhea, and necrotic enteritis. Yet, the reservoirs of enteropathogenic enterotoxin-producing strains remain unknown. We conducted a genomic comparison of 290 strains and a heat resistance phenotyping of 30 C. perfringens strains to elucidate the population structure and ecology of this pathogen. C. perfringens genomes shared a conserved genetic backbone with more than half of the genes of an average genome conserved in >95% of strains. The cpe-carrying isolates were found to share genetic context: the cpe-carrying plasmids had different distribution patterns within the genetic lineages and the estimated pan genome of cpe-carrying isolates had a larger core genome and a smaller accessory genome compared to that of 290 strains. We characterize cpe-negative strains related to chromosomal cpe-carrying strains elucidating the origin of these strains and disclose two distinct groups of chromosomal cpe-carrying strains with different virulence characteristics, spore heat resistance properties, and, presumably, ecological niche. Finally, an antibiotic-associated diarrhea isolate carrying two copies of the enterotoxin cpe gene and the associated genetic lineage with the potential for the emergence of similar strains are outlined. With C. perfringens as an example, implications of input genome quality for pan genome analysis are discussed. Our study furthers the understanding of genome epidemiology and population structure of enteropathogenic C. perfringens and brings new insight into this important pathogen and its reservoirs.}, }
@article {pmid34566693, year = {2021}, author = {Busing, JD and Buendia, M and Choksi, Y and Hiremath, G and Das, SR}, title = {Microbiome in Eosinophilic Esophagitis-Metagenomic, Metatranscriptomic, and Metabolomic Changes: A Systematic Review.}, journal = {Frontiers in physiology}, volume = {12}, number = {}, pages = {731034}, pmid = {34566693}, issn = {1664-042X}, support = {IK2 BX004648/BX/BLRD VA/United States ; }, abstract = {Background: Our understanding of human gut microbiota has expanded in recent years with the introduction of high-throughput sequencing methods. These technologies allow for the study of metagenomic, metatranscriptomic, and metabolomic bacterial alterations as they relate to human disease. Work in this area has described the human gut microbiome in both healthy individuals and those with chronic gastrointestinal diseases, such as eosinophilic esophagitis (EoE). Objectives: A systematic review of the current available literature on metagenomic, metatranscriptomic, and metabolomic changes in EoE was performed. Methods: This review was performed following the PRISMA guidelines for reporting systematic reviews and meta-analyses. All relevant publications up to March 2021 were retrieved using the search engines PubMed, Google Scholar, and Web of Science. They were then extracted, assessed, and reviewed. Only original studies published in English were included. Results: A total of 46 potential manuscripts were identified for review. Twelve met criteria for further review based on relevance screening and 9 met criteria for inclusion, including 6 studies describing the microbiome in EoE and 3 detailing metabolomic/tissue biochemistry alterations in EoE. No published studies examined metatranscriptomic changes. Samples for microbiome analysis were obtained via esophageal biopsy (n = 3), esophageal string test (n = 1), salivary sampling (n = 1), or stool specimen (n = 1). Samples analyzing tissue biochemistry were obtained via esophageal biopsy (n = 2) and blood plasma (n = 1). There were notable differences in how samples were collected and analyzed. Metabolomic and tissue biochemical alterations were described using Raman spectroscopy, which demonstrated distinct differences in the spectral intensities of glycogen, lipid, and protein content compared to controls. Finally, research in proteomics identified an increase in the pro-fibrotic protein thrombospondin-1 in patients with EoE compared with controls. Conclusions: While there are notable changes in the microbiome, these differ with the collection technique and method of analysis utilized. Techniques characterizing metabolomics and tissue biochemistry are now being utilized to further study patients with EoE. The lack of published data related to the human microbiome, metagenome, metatranscriptome, and metabolome in patients with EoE highlights the need for further research in these areas.}, }
@article {pmid34560884, year = {2021}, author = {Kumpitsch, C and Fischmeister, FPS and Mahnert, A and Lackner, S and Wilding, M and Sturm, C and Springer, A and Madl, T and Holasek, S and Högenauer, C and Berg, IA and Schoepf, V and Moissl-Eichinger, C}, title = {Reduced B12 uptake and increased gastrointestinal formate are associated with archaeome-mediated breath methane emission in humans.}, journal = {Microbiome}, volume = {9}, number = {1}, pages = {193}, pmid = {34560884}, issn = {2049-2618}, support = {I 3792/FWF_/Austrian Science Fund FWF/Austria ; P 28854/FWF_/Austrian Science Fund FWF/Austria ; W 1226/FWF_/Austrian Science Fund FWF/Austria ; }, mesh = {Adult ; Animals ; Female ; Formates ; Gastrointestinal Tract ; Humans ; Male ; Metagenomics ; *Methane ; *Methanobrevibacter/genetics ; Rumen ; Young Adult ; }, abstract = {BACKGROUND: Methane is an end product of microbial fermentation in the human gastrointestinal tract. This gas is solely produced by an archaeal subpopulation of the human microbiome. Increased methane production has been associated with abdominal pain, bloating, constipation, IBD, CRC or other conditions. Twenty percent of the (healthy) Western populations innately exhale substantially higher amounts (>5 ppm) of this gas. The underlying principle for differential methane emission and its effect on human health is not sufficiently understood.<br><br>RESULTS: We assessed the breath methane content,&#xa0;the gastrointestinal microbiome,&#xa0;its function&#xa0;and metabolome, and dietary intake of one-hundred healthy young adults (female: n = 52, male: n = 48; mean age =24.1). On the basis of the amount of methane emitted, participants were grouped into high methane emitters (CH4 breath content 5-75 ppm) and low emitters (CH4 < 5 ppm). The microbiomes of high methane emitters were characterized by a 1000-fold increase in Methanobrevibacter smithii. This archaeon co-occurred with a bacterial community specialized on dietary fibre degradation, which included members of Ruminococcaceae and Christensenellaceae. As confirmed by metagenomics and metabolomics, the biology of high methane producers was further characterized by increased formate and acetate levels in the gut. These metabolites were strongly correlated with dietary habits, such as vitamin, fat and fibre intake, and microbiome function, altogether driving archaeal methanogenesis.<br><br>CONCLUSIONS: This study enlightens the complex, multi-level interplay of host diet, genetics and microbiome composition/function leading to two fundamentally different gastrointestinal phenotypes and identifies novel points of therapeutic action in methane-associated disorders. Video Abstract.}, }
@article {pmid34559283, year = {2021}, author = {Bajerski, F and Nagel, M and Overmann, J}, title = {Microbial occurrence in liquid nitrogen storage tanks: a challenge for cryobanking?.}, journal = {Applied microbiology and biotechnology}, volume = {105}, number = {20}, pages = {7635-7650}, pmid = {34559283}, issn = {1432-0614}, mesh = {*Cryopreservation ; Gases ; Humans ; *Nitrogen ; Temperature ; }, abstract = {Modern biobanks maintain valuable living materials for medical diagnostics, reproduction medicine, and conservation purposes. To guarantee high quality during long-term storage and to avoid metabolic activities, cryostorage is often conducted in the N2 vapour phase or in liquid nitrogen (LN) at temperatures below - 150 °C. One potential risk of cryostorage is microbial cross contamination in the LN storage tanks. The current review summarises data on the occurrence of microorganisms that may compromise the safety and quality of biological materials during long-term storage. We assess the potential for the microbial contamination of LN in storage tanks holding different biological materials based on the detection by culture-based and molecular approaches. The samples themselves, the LN, the human microbiome, and the surrounding environment are possible routes of contamination and can cause cross contaminations via the LN phase. In general, the results showed that LN is typically not the source of major contaminations and only a few studies provided evidence for a risk of microbial cross contamination. So far, culture-based and culture-independent techniques detected only low amounts of microbial cells, indicating that cross contamination may occur at a very low frequency. To further minimise the potential risk of microbial cross contaminations, we recommend reducing the formation of ice crystals in cryotanks that can entrap environmental microorganisms and using sealed or second sample packing. A short survey demonstrated the awareness for microbial contaminations of storage containers among different culture collections. Although most participants consider the risk of cross contaminations in LN storage tanks as low, they prevent potential contaminations by using sealed devices and - 150 °C freezers. It is concluded that the overall risk for cross contaminations in biobanks is relatively low when following standard operating procedures (SOPs). We evaluated the potential sources in detail and summarised our results in a risk assessment spreadsheet which can be used for the quality management of biobanks. KEY POINTS: • Identification of potential contaminants and their sources in LN storage tanks. • Recommendations to reduce this risk of LN storage tank contamination. • Development of a risk assessment spreadsheet to support quality management.}, }
@article {pmid34559210, year = {2021}, author = {Klein, K and Garkov, D and Rütschlin, S and Böttcher, T and Schreiber, F}, title = {QSDB-a graphical Quorum Sensing Database.}, journal = {Database : the journal of biological databases and curation}, volume = {2021}, number = {}, pages = {}, pmid = {34559210}, issn = {1758-0463}, mesh = {Humans ; *Microbiota ; *Quorum Sensing ; }, abstract = {The human microbiome is largely shaped by the chemical interactions of its microbial members, which includes cross-talk via shared signals or quenching of the signalling of other species. Quorum sensing is a process that allows microbes to coordinate their behaviour in dependence of their population density and to adjust gene expression accordingly. We present the Quorum Sensing Database (QSDB), a comprehensive database of all published sensing and quenching relations between organisms and signalling molecules of the human microbiome, as well as an interactive web interface that allows browsing the database, provides graphical depictions of sensing mechanisms as Systems Biology Graphical Notation diagrams and links to other databases. Database URL: QSDB (Quorum Sensing DataBase) is freely available via an interactive web interface and as a downloadable csv file at http://qsdb.org.}, }
@article {pmid34555832, year = {2022}, author = {Zafar, H and Saier, MH}, title = {Comparative Analyses of the Transport Proteins Encoded within the Genomes of nine Bifidobacterium Species.}, journal = {Microbial physiology}, volume = {32}, number = {1-2}, pages = {30-44}, pmid = {34555832}, issn = {2673-1673}, support = {R01 GM077402/GM/NIGMS NIH HHS/United States ; }, mesh = {Bifidobacterium/genetics ; *Bifidobacterium bifidum ; Carrier Proteins/metabolism ; *Gastrointestinal Microbiome/genetics ; Humans ; Infant, Newborn ; *Probiotics ; }, abstract = {The human microbiome influences human health in both negative and positive ways. Studies on the transportomes of these organisms yield information that may be utilized for various purposes, including the identification of novel drug targets and the manufacture of improved probiotic strains. Moreover, these genomic analyses help to improve our understanding of the physiology and metabolic capabilities of these organisms. The present study is a continuation of our studies on the transport proteins of the major gut microbes. Bifidobacterium species are essential members of the human gut microbiome, and they initiate colonization of the gut at birth, providing health benefits that last a lifetime. In this study we analyze the transportomes of nine bifidobacterial species: B. adolescentis, B. animalis, B. bifidum, B. breve, B. catenulatum, B. dentium, B. longum subsp. infantis, B. longum subsp. longum, and B. pseudocatenulatum. All of these species have proven probiotic characteristics and exert beneficial effects on human health. Surprisingly, we found that all nine of these species have similar pore-forming toxins and drug exporters that may play roles in pathogenesis. These species have transporters for amino acids, carbohydrates, and proteins, essential for their organismal lifestyles and adaption to their respective ecological niches. The strictly probiotic species, B. bifidum, however, contains fewer such transporters, thus indicative of limited interactions with host cells and other gut microbial counterparts. The results of this study were compared with those of our previous studies on the transportomes of multiple species of Bacteroides, Escherichia coli/Salmonella, and Lactobacillus. Overall, bifidobacteria have larger transportomes (based on percentages of total proteins) than the previously examined groups of bacterial species, with a preference for primary active transport systems over secondary carriers. Taken together, these results provide useful information about the physiologies and pathogenic potentials of these probiotic organisms as reflected by their transportomes.}, }
@article {pmid34554215, year = {2022}, author = {Bodein, A and Scott-Boyer, MP and Perin, O and Lê Cao, KA and Droit, A}, title = {timeOmics: an R package for longitudinal multi-omics data integration.}, journal = {Bioinformatics (Oxford, England)}, volume = {38}, number = {2}, pages = {577-579}, doi = {10.1093/bioinformatics/btab664}, pmid = {34554215}, issn = {1367-4811}, support = {//Research and Innovation chair L'Or&#xe9;al in Digital Biology/ ; GNT1159458//National Health and Medical Research Council (NHMRC) Career Development fellowship/ ; }, mesh = {Humans ; *Genomics/methods ; *Multiomics ; Cluster Analysis ; }, abstract = {MOTIVATION: Multi-omics data integration enables the global analysis of biological systems and discovery of new biological insights. Multi-omics experimental designs have been further extended with a longitudinal dimension to study dynamic relationships between molecules. However, methods that integrate longitudinal multi-omics data are still in their infancy.<br><br>RESULTS: We introduce the R package timeOmics, a generic analytical framework for the integration of longitudinal multi-omics data. The framework includes pre-processing, modeling and clustering to identify molecular features strongly associated with time. We illustrate this framework in a case study to detect seasonal patterns of mRNA, metabolites, gut taxa and clinical variables in patients with diabetes mellitus from the integrative Human Microbiome Project.<br><br>timeOmics is available on Bioconductor and github.com/abodein/timeOmics.<br><br>SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.}, }
@article {pmid34546072, year = {2021}, author = {Flores Ramos, S and Brugger, SD and Escapa, IF and Skeete, CA and Cotton, SL and Eslami, SM and Gao, W and Bomar, L and Tran, TH and Jones, DS and Minot, S and Roberts, RJ and Johnston, CD and Lemon, KP}, title = {Genomic Stability and Genetic Defense Systems in Dolosigranulum pigrum, a Candidate Beneficial Bacterium from the Human Microbiome.}, journal = {mSystems}, volume = {6}, number = {5}, pages = {e0042521}, pmid = {34546072}, issn = {2379-5077}, support = {R01 DE027850/DE/NIDCR NIH HHS/United States ; R01 GM117174/GM/NIGMS NIH HHS/United States ; Stimulus Pilot Grant//The Forsyth Institute/ ; P3SMP3_155315//Swiss National Science Foundation and Swiss Foundation for Grants in Biology and Medicine/ ; R01 DE027850/DE/NIDCR NIH HHS/United States ; R01 GM117174/GM/NIGMS NIH HHS/United States ; 16B065//Novartis Stiftung&#xa0;f&#xfc;r&#xa0;Medizinisch-Biologische Forschung (Novartis Foundation for Medical-Biological Research)/ ; 1449/M//Promedica Stiftung/ ; }, abstract = {Dolosigranulum pigrum is positively associated with indicators of health in multiple epidemiological studies of human nasal microbiota. Knowledge of the basic biology of D. pigrum is a prerequisite for evaluating its potential for future therapeutic use; however, such data are very limited. To gain insight into D. pigrum's chromosomal structure, pangenome, and genomic stability, we compared the genomes of 28 D. pigrum strains that were collected across 20 years. Phylogenomic analysis showed closely related strains circulating over this period and closure of 19 genomes revealed highly conserved chromosomal synteny. Gene clusters involved in the mobilome and in defense against mobile genetic elements (MGEs) were enriched in the accessory genome versus the core genome. A systematic analysis for MGEs identified the first candidate D. pigrum prophage and insertion sequence. A systematic analysis for genetic elements that limit the spread of MGEs, including restriction modification (RM), CRISPR-Cas, and deity-named defense systems, revealed strain-level diversity in host defense systems that localized to specific genomic sites, including one RM system hot spot. Analysis of CRISPR spacers pointed to a wealth of MGEs against which D. pigrum defends itself. These results reveal a role for horizontal gene transfer and mobile genetic elements in strain diversification while highlighting that in D. pigrum this occurs within the context of a highly stable chromosomal organization protected by a variety of defense mechanisms. IMPORTANCE Dolosigranulum pigrum is a candidate beneficial bacterium with potential for future therapeutic use. This is based on its positive associations with characteristics of health in multiple studies of human nasal microbiota across the span of human life. For example, high levels of D. pigrum nasal colonization in adults predicts the absence of Staphylococcus aureus nasal colonization. Also, D. pigrum nasal colonization in young children is associated with healthy control groups in studies of middle ear infections. Our analysis of 28 genomes revealed a remarkable stability of D. pigrum strains colonizing people in the United States across a 20-year span. We subsequently identified factors that can influence this stability, including genomic stability, phage predators, the role of MGEs in strain-level variation, and defenses against MGEs. Finally, these D. pigrum strains also lacked predicted virulence factors. Overall, these findings add additional support to the potential for D. pigrum as a therapeutic bacterium.}, }
@article {pmid34545840, year = {2021}, author = {Dery, KJ and Kupiec-Weglinski, JW and Dong, TS}, title = {The human microbiome in transplantation: the past, present, and future.}, journal = {Current opinion in organ transplantation}, volume = {26}, number = {6}, pages = {595-602}, doi = {10.1097/MOT.0000000000000922}, pmid = {34545840}, issn = {1531-7013}, mesh = {High-Throughput Nucleotide Sequencing ; Humans ; *Metagenomics ; *Microbiota ; }, abstract = {PURPOSE OF REVIEW: Over the past 20 years, DNA sequencing technology has transformed human microbiome research from identity characterizations to metagenomics approaches that reveal how microbials correlate with human health and disease. New studies are showing unprecedented opportunity for deep characterization of the human microbial ecosystem, with benefits to the field of organ transplantation.<br><br>RECENT FINDINGS: In the present review, we focus on past milestones of human-associated microbiota research, paying homage to microbiota pioneers. We highlight the role of sequencing efforts to provide insights beyond taxonomic identification. Recent advances in microbiome technology is now integrating high-throughput datasets, giving rise to multi'omics - a comprehensive assessment modeling dynamic biologic networks. Studies that show benefits and mechanisms in peritransplant antibiotic (Abx)-conditioned recipients are reviewed. We describe how next-generation microbial sequencing has the potential to combine with new technologies like phage therapy (PT) to translate into life-saving therapeutics.<br><br>SUMMARY: The study of the microbiome is advancing the field of transplantation by enhancing our knowledge of precision medicine. Sequencing technology has allowed the use of the microbiome as a biomarker to risk stratify patients. Further research is needed to better understand how microbiomes shape transplantation outcomes while informing immune cell - tissue crosstalk platforms.}, }
@article {pmid34536920, year = {2022}, author = {Samarrai, R and Frank, S and Lum, A and Woodis, K and Weinstock, G and Roberts, D}, title = {Defining the microbiome of the head and neck: A contemporary review.}, journal = {American journal of otolaryngology}, volume = {43}, number = {1}, pages = {103224}, doi = {10.1016/j.amjoto.2021.103224}, pmid = {34536920}, issn = {1532-818X}, mesh = {Anti-Bacterial Agents/therapeutic use ; Dysbiosis/microbiology ; Ear/*microbiology ; Head/*microbiology ; Humans ; *Microbiota ; Neck/*microbiology ; }, abstract = {OBJECTIVE: The purpose of this paper is to define the microbiome of the head and neck by characterizing and distinguishing the commensal bacteria from pathogenic species.<br><br>STUDY DESIGN: Literature review.<br><br>METHODS: Pubmed and Google scholar databases were queried for relevant articles. Keywords such as "middle ear microbiome", "outer ear microbiome", "sinonasal microbiome", "tonsil microbiome", and "laryngeal microbiome" were utilized separately to identify articles pertaining to each topic of study. All applicable abstracts were chosen for initial review and relevant abstracts were then selected for review of the full texts. Articles that did not study the human microbiome, those not written primarily in English, those that were not readily available for full review, and case reports were excluded from the study.<br><br>RESULTS: Limited studies that investigate the microbial environments of isolated anatomic subsites in the head and neck exist, however the comprehensive microbiome of the head and neck has yet to be completely defined. Based on this review, various studies of the ears, larynx, tonsils and sinus microbiomes exist and yield valuable information, however they are limited in scope and anatomic subsite. In this literature review, these studies are compiled in order to create a comprehensive text inclusive of the known microbial elements of the major anatomic subsites of the head and neck, namely the tonsils, larynx, sinus, outer ear and middle ear.<br><br>CONCLUSIONS: The significance of the human microbiome in identifying and preventing disease has been established in various physiologic systems, however there is limited research on the microbiome of the head and neck. Understanding the microbiome of the head and neck can help differentiate disease-prone patients from normal patients and guide treatment regimens and antibiotic usage, to aid in resistance control and limit adverse effects of antibiotic overuse. Understanding the elements that lead to dysbiosis can help treat and even prevent common conditions as tonsillitis and rhinosinusitis. In this review, we provide a comprehensive review to serve as an initial background for future studies to define the head and neck microbiome distinguished by all relevant subsites.}, }
@article {pmid34531833, year = {2021}, author = {Ezzamouri, B and Shoaie, S and Ledesma-Amaro, R}, title = {Synergies of Systems Biology and Synthetic Biology in Human Microbiome Studies.}, journal = {Frontiers in microbiology}, volume = {12}, number = {}, pages = {681982}, pmid = {34531833}, issn = {1664-302X}, abstract = {A number of studies have shown that the microbial communities of the human body are integral for the maintenance of human health. Advances in next-generation sequencing have enabled rapid and large-scale quantification of the composition of microbial communities in health and disease. Microorganisms mediate diverse host responses including metabolic pathways and immune responses. Using a system biology approach to further understand the underlying alterations of the microbiota in physiological and pathological states can help reveal potential novel therapeutic and diagnostic interventions within the field of synthetic biology. Tools such as biosensors, memory arrays, and engineered bacteria can rewire the microbiome environment. In this article, we review the computational tools used to study microbiome communities and the current limitations of these methods. We evaluate how genome-scale metabolic models (GEMs) can advance our understanding of the microbe-microbe and microbe-host interactions. Moreover, we present how synergies between these system biology approaches and synthetic biology can be harnessed in human microbiome studies to improve future therapeutics and diagnostics and highlight important knowledge gaps for future research in these rapidly evolving fields.}, }
@article {pmid34531252, year = {2022}, author = {Pinto, D and Trink, A and Giuliani, G and Rinaldi, F}, title = {Protective effects of sunscreen (50+) and octatrienoic acid 0.1% in actinic keratosis and UV damages.}, journal = {Journal of investigative medicine : the official publication of the American Federation for Clinical Research}, volume = {70}, number = {1}, pages = {92-98}, pmid = {34531252}, issn = {1708-8267}, mesh = {Humans ; *Keratosis, Actinic/prevention &amp; control ; Skin ; Sun Protection Factor ; Sunburn/*drug therapy/prevention &amp; control ; Sunscreening Agents/*pharmacology/therapeutic use ; Ultraviolet Rays/*adverse effects ; }, abstract = {Actinic keratosis is a form of dysplastic epidermal lesion resulting from chronic and excessive UV exposure with a certain risk of becoming cancerous. Current guidelines advocated the use of sunscreens to prevent photodamage. An efficient photoprotection must involve both primary protective factors such as UV filters and secondary factors (eg, antioxidants) able to disrupt the photochemical and genetic cascade triggered by UVs. An in vitro model of human skin (Phenion FT) was used to assess the photoprotective potential of a sunscreen containing inorganic sun-filters (50+ SPF) and 0.1% octatrienoic acid (KERA'+) after UVA (10 J/cm[2]) and UVB (25 mJ/cm[2]) by means of evaluation of the number of sunburn cells (SBCs) and apoptotic keratinocytes. Also resulting alterations in the gene expression of markers involved in apoptosis (Tumor protein 53), inflammation/immunosuppression (IL-6 and IL-8), oxidative stress (oxidative stress response enzyme heme oxygenase 1), remodeling (metalloproteinase 1) and cell-cell adhesion (E-cadherin) were investigated. Gene expression was investigated using quantitative real-time PCR. This work demonstrated that the sunscreen preparations under study (with and without 0.1% octatrienoic acid, respectively) can be distinguished about their ability to prevent UVs-induced damage. Synergism between the inorganic filters and 0.1% octatrienoic acid was found (KERA'+) on all end points analyzed and this effect was found to be statistically significant (p<0.05). Our data revealed that topical application of a sunscreen containing inorganic filters (50+SPF) and 0.1% octatrienoic acid can protect from SBC formation, reduce the number of apoptotic keratinocytes and protect from the main molecular alterations caused by UV radiations.}, }
@article {pmid34525957, year = {2021}, author = {Wang, C and Hu, J and Blaser, MJ and Li, H}, title = {Microbial trend analysis for common dynamic trend, group comparison, and classification in longitudinal microbiome study.}, journal = {BMC genomics}, volume = {22}, number = {1}, pages = {667}, pmid = {34525957}, issn = {1471-2164}, support = {R01 DK110014/DK/NIDDK NIH HHS/United States ; R01DK110014//foundation for the national institutes of health/ ; U01AI22285//foundation for the national institutes of health/ ; 1P20CA252728//foundation for the national institutes of health/ ; P20 CA252728/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; *Computational Biology ; Longitudinal Studies ; Mice ; *Microbiota ; }, abstract = {BACKGROUND: The human microbiome is inherently dynamic and its dynamic nature plays a critical role in maintaining health and driving disease. With an increasing number of longitudinal microbiome studies, scientists are eager to learn the comprehensive characterization of microbial dynamics and their implications to the health and disease-related phenotypes. However, due to the challenging structure of longitudinal microbiome data, few analytic methods are available to characterize the microbial dynamics over time.<br><br>RESULTS: We propose a microbial trend analysis (MTA) framework for the high-dimensional and phylogenetically-based longitudinal microbiome data. In particular, MTA can perform three tasks: 1) capture the common microbial dynamic trends for a group of subjects at the community level and identify the dominant taxa; 2) examine whether or not the microbial overall dynamic trends are significantly different between groups; 3) classify an individual subject based on its longitudinal microbial profiling. Our extensive simulations demonstrate that the proposed MTA framework is robust and powerful in hypothesis testing, taxon identification, and subject classification. Our real data analyses further illustrate the utility of MTA through a longitudinal study in mice.<br><br>CONCLUSIONS: The proposed MTA framework is an attractive and effective tool in investigating dynamic microbial pattern from longitudinal microbiome studies.}, }
@article {pmid34525400, year = {2021}, author = {Giufrè, M and Mazzolini, E and Cerquetti, M and Brusaferro, S and , }, title = {Extended-spectrum β-lactamase-producing Escherichia coli from extraintestinal infections in humans and from food-producing animals in Italy: a 'One Health' study.}, journal = {International journal of antimicrobial agents}, volume = {58}, number = {5}, pages = {106433}, doi = {10.1016/j.ijantimicag.2021.106433}, pmid = {34525400}, issn = {1872-7913}, mesh = {Animals ; Anti-Bacterial Agents/pharmacology ; Bacterial Proteins/*genetics ; Cattle ; Cross-Sectional Studies ; Drug Resistance, Multiple, Bacterial/*genetics ; Escherichia coli/drug effects/*genetics/isolation &amp; purification ; Escherichia coli Infections/*veterinary ; Escherichia coli Proteins/genetics ; Humans ; Italy ; Microbial Sensitivity Tests ; Molecular Epidemiology ; Multilocus Sequence Typing ; Poultry/microbiology ; Swine/microbiology ; beta-Lactamases/*genetics ; }, abstract = {Recently, Escherichia coli producing extended-spectrum β-lactamases (ESBLs) have become a serious public-health problem, and food-producing animals (FPAs) have been suggested as a potential reservoir/source. This study aimed to compare ESBL-producing E. coli isolates from different sources. ESBL-producing E. coli isolates were collected from humans (n = 480) and FPAs (n = 445) in Italy (2016-2017). Isolates were screened for the presence of ESBL and carbapenemase genes and were classified according to phylogenetic group and MLST genotyping. The genes mcr-1 to -5 were searched for in colistin-resistant isolates. CTX-M was the most frequent ESBL type both in human and animal isolates. CTX-M-15 prevailed in humans (75.0%) and cattle (51.1%) but not in poultry (36.6%). CTX-M-1 was common (58.3%) in pigs. SHV-type and CMY-2-like were found in FPAs, especially in poultry (17.0% and 29.9%, respectively). Additionally, 29 isolates were mcr-1 carriers (3 from humans and 26 from FPAs). No carbapenemase genes were detected. Human isolates mostly belonged to phylogroup B2 (76.5%). Animal isolates were distributed among groups A (35.7%), B1 (26.1%) and C (12.4%). Few animal isolates (almost all from poultry) were classified into group B2 (4.3%). Most human isolates (83.4%) belonged to the pandemic ST131 clone and frequently carried CTX-M-15 (75.9%). ST131 was rarely detected in FPAs (three isolates from poultry). Nineteen STs were shared in both sources, with ST10, ST410 and ST69 being more frequently detected. Potential exchange of ESBL genes from animals to humans is feasible, underlying the need for strict monitoring based on a 'One Health' approach.}, }
@article {pmid34524796, year = {2021}, author = {Wernke, KM and Tirla, A and Xue, M and Surovtseva, YV and Menges, FS and Herzon, SB}, title = {Probing Microbiome Genotoxicity: A Stable Colibactin Provides Insight into Structure-Activity Relationships and Facilitates Mechanism of Action Studies.}, journal = {Journal of the American Chemical Society}, volume = {143}, number = {38}, pages = {15824-15833}, doi = {10.1021/jacs.1c07559}, pmid = {34524796}, issn = {1520-5126}, support = {T32 GM067543/GM/NIGMS NIH HHS/United States ; R01 CA215553/CA/NCI NIH HHS/United States ; }, mesh = {DNA/chemistry ; Escherichia coli/genetics ; Escherichia coli Proteins/*chemical synthesis ; Humans ; Microbiota/genetics ; Molecular Conformation ; Multigene Family ; Mutagens/metabolism ; Mutation ; Oxidation-Reduction ; Peptides/*chemical synthesis ; Phenotype ; Polyketides/*chemical synthesis ; Protein Binding ; Structure-Activity Relationship ; }, abstract = {Colibactin is a genotoxic metabolite produced by commensal-pathogenic members of the human microbiome that possess the clb (aka pks) biosynthetic gene cluster. clb[+] bacteria induce tumorigenesis in models of intestinal inflammation and have been causally linked to oncogenesis in humans. While colibactin is believed underlie these effects, it has not been possible to study the molecule directly due to its instability. Herein, we report the synthesis and biological studies of colibactin 742 (4), a stable colibactin derivative. We show that colibactin 742 (4) induces DNA interstrand-cross-links, activation of the Fanconi Anemia DNA repair pathway, and G2/M arrest in a manner similar to clb[+]E. coli. The linear precursor 9, which mimics the biosynthetic precursor to colibactin, also recapitulates the bacterial phenotype. In the course of this work, we discovered a novel cyclization pathway that was previously undetected in MS-based studies of colibactin, suggesting a refinement to the natural product structure and its mode of DNA binding. Colibactin 742 (4) and its precursor 9 will allow researchers to study colibactin's genotoxic effects independent of the producing organism for the first time.}, }
@article {pmid34523995, year = {2021}, author = {Brycki, JD and Chen See, JR and Letson, GR and Emlet, CS and Unverdorben, LV and Heibeck, NS and Brislawn, CJ and Buonaccorsi, VP and Chan, JP and Lamendella, R}, title = {Temporal Transcriptomics of Gut Escherichia coli in Caenorhabditis elegans Models of Aging.}, journal = {Microbiology spectrum}, volume = {9}, number = {2}, pages = {e0049821}, pmid = {34523995}, issn = {2165-0497}, support = {R15 AG052933/AG/NIA NIH HHS/United States ; R15 AG063103/AG/NIA NIH HHS/United States ; }, mesh = {Aging/*genetics/metabolism ; Animals ; Caenorhabditis elegans/genetics/growth &amp; development/metabolism/*microbiology ; Disease Models, Animal ; Escherichia coli/*genetics/metabolism ; Escherichia coli Proteins/*genetics/metabolism ; Female ; *Gastrointestinal Microbiome ; Humans ; Male ; Transcriptome ; }, abstract = {Host-bacterial interactions over the course of aging are understudied due to complexities of the human microbiome and challenges of collecting samples that span a lifetime. To investigate the role of host-microbial interactions in aging, we performed transcriptomics using wild-type Caenorhabditis elegans (N2) and three long-lived mutants (daf-2, eat-2, and asm-3) fed Escherichia coli OP50 and sampled at days 5, 7.5, and 10 of adulthood. We found host age is a better predictor of the E. coli expression profiles than host genotype. Specifically, host age was associated with clustering (permutational multivariate analysis of variance [PERMANOVA], P = 0.001) and variation (Adonis, P = 0.001, R[2] = 11.5%) among E. coli expression profiles, whereas host genotype was not (PERMANOVA, P > 0.05; Adonis, P > 0.05, R[2] = 5.9%). Differential analysis of the E. coli transcriptome yielded 22 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways and 100 KEGG genes enriched when samples were grouped by time point [LDA, linear discriminant analysis; log(LDA), ≥2; P ≤ 0.05], including several involved in biofilm formation. Coexpression analysis of host and bacterial genes yielded six modules of C. elegans genes that were coexpressed with one bacterial regulator gene over time. The three most significant bacterial regulators included genes relating to biofilm formation, lipopolysaccharide production, and thiamine biosynthesis. Age was significantly associated with clustering and variation among transcriptomic samples, supporting the idea that microbes are active and plastic within C. elegans throughout life. Coexpression analysis further revealed interactions between E. coli and C. elegans that occurred over time, building on a growing literature of host-microbial interactions. IMPORTANCE Previous research has reported effects of the microbiome on health span and life span of Caenorhabditis elegans, including interactions with evolutionarily conserved pathways in humans. We build on this literature by reporting the gene expression of Escherichia coli OP50 in wild-type (N2) and three long-lived mutants of C. elegans. The manuscript represents the first study, to our knowledge, to perform temporal host-microbial transcriptomics in the model organism C. elegans. Understanding changes to the microbial transcriptome over time is an important step toward elucidating host-microbial interactions and their potential relationship to aging. We found that age was significantly associated with clustering and variation among transcriptomic samples, supporting the idea that microbes are active and plastic within C. elegans throughout life. Coexpression analysis further revealed interactions between E. coli and C. elegans that occurred over time, which contributes to our growing knowledge about host-microbial interactions.}, }
@article {pmid34522484, year = {2021}, author = {Patel, P and Poudel, A and Kafle, S and Thapa Magar, M and Cancarevic, I}, title = {Influence of Microbiome and Antibiotics on the Efficacy of Immune Checkpoint Inhibitors.}, journal = {Cureus}, volume = {13}, number = {8}, pages = {e16829}, pmid = {34522484}, issn = {2168-8184}, abstract = {The human microbiome mainly consists of bacteria and interacts closely with the immune system. Immune checkpoint inhibitors (ICI) are used to treat several types of cancers. Recently, it has been identified that the gut microbiome plays a role in the effectiveness of immunotherapy. This study aims to analyze the effect of microbiome and antibiotics on the effectiveness of ICI in cancer patients and the measures to improve efficacy based on that. A detailed review was conducted on articles published in PubMed and Science Direct in the last five years i.e., 2016 to 2021. A total of 16 articles involving 1293 patients with cancer who were receiving immunotherapy, were deemed eligible to be included in the final review. Data were extracted from the eligible articles and were checked for quality appraisal. All 16 articles revealed the effect of either gut microbiome or antibiotics or both on ICI. Based on our findings, we found that the microbiome enriched in different microorganisms responded differently to the ICI and that antibiotics negatively impacted the effectiveness of ICI. The time at which patients receiving ICI were prescribed antibiotics influenced the effect of ICI. Antibiotics and different microbiome also affected progression-free survival (PFS) and overall survival (OS).}, }
@article {pmid34520499, year = {2021}, author = {Carr, C and Wilcox, H and Burton, JP and Menon, S and Al, KF and O'Gorman, D and Lanting, BA and Vasarhelyi, EM and Neufeld, M and Teeter, MG}, title = {Deciphering the low abundance microbiota of presumed aseptic hip and knee implants.}, journal = {PloS one}, volume = {16}, number = {9}, pages = {e0257471}, pmid = {34520499}, issn = {1932-6203}, mesh = {Adult ; Aged ; Arthroplasty, Replacement, Hip ; Arthroplasty, Replacement, Knee ; Artifacts ; Bacteria/genetics/*isolation &amp; purification ; Female ; Hip Joint/microbiology ; Humans ; Knee Joint/microbiology ; Male ; *Microbiota ; Middle Aged ; Polymerase Chain Reaction ; Prosthesis-Related Infections/*microbiology/pathology ; RNA, Ribosomal, 16S/chemistry/genetics/metabolism ; Sequence Analysis, DNA ; }, abstract = {16S rRNA gene sequencing of DNA extracted from clinically uninfected hip and knee implant samples has revealed polymicrobial populations. However, previous studies assessed 16S rRNA gene sequencing as a technique for the diagnosis of periprosthetic joint infections, leaving the microbiota of presumed aseptic hip and knee implants largely unstudied. These communities of microorganisms might play important roles in aspects of host health, such as aseptic loosening. Therefore, this study sought to characterize the bacterial composition of presumed aseptic joint implant microbiota using next generation 16S rRNA gene sequencing, and it evaluated this method for future investigations. 248 samples were collected from implants of 41 patients undergoing total hip or knee arthroplasty revision for presumed aseptic failure. DNA was extracted using two methodologies-one optimized for high throughput and the other for human samples-and amplicons of the V4 region of the 16S rRNA gene were sequenced. Sequencing data were analyzed and compared with ancillary specific PCR and microbiological culture. Computational tools (SourceTracker and decontam) were used to detect and compensate for environmental and processing contaminants. Microbial diversity of patient samples was higher than that of open-air controls and differentially abundant taxa were detected between these conditions, possibly reflecting a true microbiota that is present in clinically uninfected joint implants. However, positive control-associated artifacts and DNA extraction methodology significantly affected sequencing results. As well, sequencing failed to identify Cutibacterium acnes in most culture- and PCR-positive samples. These challenges limited characterization of bacteria in presumed aseptic implants, but genera were identified for further investigation. In all, we provide further support for the hypothesis that there is likely a microbiota present in clinically uninfected joint implants, and we show that methods other than 16S rRNA gene sequencing may be ideal for its characterization. This work has illuminated the importance of further study of microbiota of clinically uninfected joint implants with novel molecular and computational tools to further eliminate contaminants and artifacts that arise in low bacterial abundance samples.}, }
@article {pmid34519530, year = {2021}, author = {Leclerc, M and Bedu-Ferrari, C and Etienne-Mesmin, L and Mariadassou, M and Lebreuilly, L and Tran, SL and Brazeau, L and Mayeur, C and Delmas, J and Rué, O and Denis, S and Blanquet-Diot, S and Ramarao, N}, title = {Nitric Oxide Impacts Human Gut Microbiota Diversity and Functionalities.}, journal = {mSystems}, volume = {6}, number = {5}, pages = {e0055821}, pmid = {34519530}, issn = {2379-5077}, support = {MICA-MEM//Institut National de la Recherche Agronomique (INRA)/ ; }, abstract = {The disruption of gut microbiota homeostasis has been associated with numerous diseases and with a disproportionate inflammatory response, including overproduction of nitric oxide (NO) in the intestinal lumen. However, the influence of NO on the human gut microbiota has not been well characterized yet. We used in vitro fermentation systems inoculated with human fecal samples to monitor the effect of repetitive NO pulses on the gut microbiota. NO exposure increased the redox potential and modified the fermentation profile and gas production. The overall metabolome was modified, reflecting less strict anaerobic conditions and shifts in amino acid and nitrogen metabolism. NO exposure led to a microbial shift in diversity with a decrease in Clostridium leptum group and Faecalibacterium prausnitzii biomass and an increased abundance of the Dialister genus. Escherichia coli, Enterococcus faecalis, and Proteus mirabilis operational taxonomic unit abundance increased, and strains from those species isolated after NO stress showed resistance to high NO concentrations. As a whole, NO quickly changed microbial fermentations, functions, and composition in a pulse- and dose-dependent manner. NO could shift, over time, the trophic chain to conditions that are unfavorable for strict anaerobic microbial processes, implying that a prolonged or uncontrolled inflammation has detrimental and irreversible consequences on the human microbiome. IMPORTANCE Gut microbiota dysbiosis has been associated with inflammatory diseases. The human inflammatory response leads to an overproduction of nitric oxide (NO) in the gut. However, so far, the influence of NO on the human gut microbiota has not been characterized. In this study, we used in vitro fermentation systems with human fecal samples to understand the effect of NO on the microbiota: NO modified the microbial composition and its functionality. High NO concentration depleted the microbiota of beneficial butyrate-producing species and favored potentially deleterious species (E. coli, E. faecalis, and P. mirabilis), which we showed can sustain high NO concentrations. Our work shows that NO may participate in the vicious circle of inflammation, leading to detrimental and irreversible consequences on human health.}, }
@article {pmid34517942, year = {2021}, author = {Smith, DR and Temime, L and Opatowski, L}, title = {Microbiome-pathogen interactions drive epidemiological dynamics of antibiotic resistance: A modeling study applied to nosocomial pathogen control.}, journal = {eLife}, volume = {10}, number = {}, pages = {}, pmid = {34517942}, issn = {2050-084X}, support = {164263//CIHR/Canada ; }, mesh = {Anti-Bacterial Agents/pharmacology ; Bacteria/drug effects ; Cross Infection/*epidemiology/microbiology/*prevention &amp; control ; Drug Resistance, Microbial/drug effects/*physiology ; Humans ; Microbiota/drug effects/*physiology ; Models, Theoretical ; }, abstract = {The human microbiome can protect against colonization with pathogenic antibiotic-resistant bacteria (ARB), but its impacts on the spread of antibiotic resistance are poorly understood. We propose a mathematical modeling framework for ARB epidemiology formalizing within-host ARB-microbiome competition, and impacts of antibiotic consumption on microbiome function. Applied to the healthcare setting, we demonstrate a trade-off whereby antibiotics simultaneously clear bacterial pathogens and increase host susceptibility to their colonization, and compare this framework with a traditional strain-based approach. At the population level, microbiome interactions drive ARB incidence, but not resistance rates, reflecting distinct epidemiological relevance of different forces of competition. Simulating a range of public health interventions (contact precautions, antibiotic stewardship, microbiome recovery therapy) and pathogens (Clostridioides difficile, methicillin-resistant Staphylococcus aureus, multidrug-resistant Enterobacteriaceae) highlights how species-specific within-host ecological interactions drive intervention efficacy. We find limited impact of contact precautions for Enterobacteriaceae prevention, and a promising role for microbiome-targeted interventions to limit ARB spread.}, }
@article {pmid34515049, year = {2021}, author = {Korpela, K}, title = {Impact of Delivery Mode on Infant Gut Microbiota.}, journal = {Annals of nutrition &amp; metabolism}, volume = {}, number = {}, pages = {1-9}, doi = {10.1159/000518498}, pmid = {34515049}, issn = {1421-9697}, abstract = {Microbial colonization of the neonate is an important feature of normal birth. The gut microbiota has a central role in the programming of the host's metabolism and immune function, with both immediate and long-term health consequences. During vaginal birth, the infant is exposed to diverse maternal microbes, of which specific faecal microbes colonize the infant's gut. C-section eliminates the infant's contact with maternal microbes, preventing vertical transmission of gut microbes. Consequently, infants are colonized by bacteria from the environment, including potential pathogens from the hospital environment. Recent studies have shown that intrapartum antibiotic exposure has a C-section-like effect on the infant gut microbiota. While the composition of the gut microbiota largely normalizes during the first year of life, epidemiological studies suggest that the aberrant early microbial exposures have long-term immunological and metabolic consequences. Because of the high prevalence of procedures that prevent normal gut microbiota development, effective methods to normalize the gut microbiota of neonates are urgently needed. Even more importantly, attention should be paid to the microbiota imbalance in C-section-born and antibiotic-exposed infants in clinical practice. Breastfeeding and probiotics are particularly important for infants with disrupted gut colonization.}, }
@article {pmid34509994, year = {2021}, author = {Houf, J}, title = {Faecal microbiota transplants: towards a healthy disgust scepticism.}, journal = {Medical humanities}, volume = {47}, number = {4}, pages = {407-416}, doi = {10.1136/medhum-2020-012135}, pmid = {34509994}, issn = {1473-4265}, mesh = {*Disgust ; Emotions ; Humans ; *Microbiota ; Morals ; }, abstract = {This paper engages with the obstacle of disgust surrounding the use of faecal microbiota transplants (FMT). In discourse about the human microbiome and microbiota-based therapies (like FMT), disgust has become an unavoidable emotion for physicians, patients and caregivers interested in these therapies. Additionally, microbiota therapies and microbiomes are challenging our conception of an individual biological self. As these two discourses converge with FMT, it becomes necessary to understand how they are working together. To do this, this paper explores the way disgust functions in the formation of subjects. Scholarship about disgust can be categorised into two approaches: disgust as a deep wisdom or disgust scepticism. The former approach focuses on the physiological, embodied aspects of our disgust reactions as evidence of 'truth' in disgusting encounters, and the latter recognises the way disgust is culturally contingent and adapted for use in moral and social determinations of good and bad. However, both positions accept the use of disgust as a defence against 'toxins and diseases'. Yet, as this paper argues, we should take the sceptical approach further. The disgust sceptical approach, particularly as developed by Sarah Ahmed, does more than just challenge disgust's role in moral deliberations. It also demands sceptical reflection on disgust as a universal defence against 'toxins and diseases'. Much as disgust can be co-opted to support oppression, it too can be co-opted to reconstitute a false vision of human subjectivity-the coherent, contained and exceptional human subject situated above the natural world. The human microbiome, faecal therapeutics and being disgusted give us an opportunity to recognise ourselves as more-than-human subjects.}, }
@article {pmid34506740, year = {2021}, author = {Cullin, N and Azevedo Antunes, C and Straussman, R and Stein-Thoeringer, CK and Elinav, E}, title = {Microbiome and cancer.}, journal = {Cancer cell}, volume = {39}, number = {10}, pages = {1317-1341}, doi = {10.1016/j.ccell.2021.08.006}, pmid = {34506740}, issn = {1878-3686}, mesh = {Humans ; Microbiota/*immunology ; Neoplasms/*immunology ; }, abstract = {The human microbiome constitutes a complex multikingdom community that symbiotically interacts with the host across multiple body sites. Host-microbiome interactions impact multiple physiological processes and a variety of multifactorial disease conditions. In the past decade, microbiome communities have been suggested to influence the development, progression, metastasis formation, and treatment response of multiple cancer types. While causal evidence of microbial impacts on cancer biology is only beginning to be unraveled, enhanced molecular understanding of such cancer-modulating interactions and impacts on cancer treatment are considered of major scientific importance and clinical relevance. In this review, we describe the molecular pathogenic mechanisms shared throughout microbial niches that contribute to the initiation and progression of cancer. We highlight advances, limitations, challenges, and prospects in understanding how the microbiome may causally impact cancer and its treatment responsiveness, and how microorganisms or their secreted bioactive metabolites may be potentially harnessed and targeted as precision cancer therapeutics.}, }
@article {pmid34502031, year = {2021}, author = {Bron, PA and Catalayud, M and Marzorati, M and Pane, M and Kartal, E and Dhir, R and Reid, G}, title = {Delivery of Metabolically Neuroactive Probiotics to the Human Gut.}, journal = {International journal of molecular sciences}, volume = {22}, number = {17}, pages = {}, pmid = {34502031}, issn = {1422-0067}, mesh = {*Gastrointestinal Microbiome ; Genomics ; Humans ; Limosilactobacillus reuteri/*metabolism ; Probiotics/*administration &amp; dosage ; Sequence Analysis, DNA ; Vitamin B 12/*biosynthesis ; }, abstract = {The human microbiome is a rich factory for metabolite production and emerging data has led to the concept that orally administered microbial strains can synthesize metabolites with neuroactive potential. Recent research from ex vivo and murine models suggests translational potential for microbes to regulate anxiety and depression through the gut-brain axis. However, so far, less emphasis has been placed on the selection of specific microbial strains known to produce the required key metabolites and the formulation in which microbial compositions are delivered to the gut. Here, we describe a double-capsule technology to deliver high numbers of metabolically active cells derived from the 24-strain probiotic product SH-DS01 to the gastrointestinal tract, including the small intestine, where immune responses and adsorption of metabolites into the bloodstream occur. Based on its genome sequence, Limosilactobacillus reuteri SD-LRE2-IT was predicted to have the genetic capacity to de novo produce a specific metabolite of interest to brain health, vitamin B12, which could be confirmed in vitro. Taken together, our data conceptualizes the importance of rationally defined microbial strain characterization based on genomics and metabolomics data, combined with carefully designed capsule technology for delivery of live cells and concomitant functionality in and beyond the gut ecosystem.}, }
@article {pmid34499859, year = {2021}, author = {Allen-Vercoe, E}, title = {Commensals make the most of their hosts.}, journal = {Cell host &amp; microbe}, volume = {29}, number = {9}, pages = {1337-1339}, doi = {10.1016/j.chom.2021.08.007}, pmid = {34499859}, issn = {1934-6069}, mesh = {ADP Ribose Transferases ; Humans ; *Microbiota ; *Symbiosis ; }, abstract = {In this issue of Cell Host &amp; Microbe, Brown et al. reveal a large group of genes within the human microbiome that code for ADP-ribosyltransferases that are predicted to manipulate host cells. Previously studied for pathogens, these host modification mechanisms may also be common properties of commensals.}, }
@article {pmid34494564, year = {2021}, author = {Wiqoyah, N and Mertaniasih, NM and Artama, WT and Matsumoto, S}, title = {Microbiome in sputum as a potential biomarker of chronicity in pulmonary resistant to rifampicin-tuberculosis and multidrug-resistant-tuberculosis patients.}, journal = {International journal of mycobacteriology}, volume = {10}, number = {3}, pages = {260-267}, doi = {10.4103/ijmy.ijmy_132_21}, pmid = {34494564}, issn = {2212-554X}, mesh = {Antitubercular Agents/therapeutic use ; Biomarkers ; Humans ; *Microbiota ; *Mycobacterium tuberculosis/genetics ; Rifampin ; Sputum ; *Tuberculosis, Multidrug-Resistant/drug therapy ; }, abstract = {BACKGROUND: Cases of tuberculosis (TB) and multidrug-resistant TB (MDR-TB) in South-east Asia including Indonesia are still high. The presence of mixed infections in TB cases has been reported. Several studies revealed the role of the human microbiome in TB. This study purposes to characterize microbiome which can be a potential biomarker of chronicity in TB or MDR-TB.<br><br>METHODS: Sputum samples of pulmonary TB patients confirmed MDR-TB and resistant to rifampicin TB (RR-TB) were conducted Metagenomic next-generation sequencing. Principal coordinate analysis of UniFrac's showing the community structure of microbiome in MDR-TB comorbid diabetes mellitus (DM) is different from RR-TB noncomorbid DM (P = 0.003).<br><br>RESULTS: Proteobacteria microbiome in MDR-TB comorbid DM was more abundant than in RR-TB noncomorbid DM. Actinobacteria found in the small quantity in RR-TB and MDR-TB. Diversity of microbiome genera was greater in RR-TB. The linear discriminant analysis effect size analysis represents a genus biomarker whose abundance shows significant differences between groups, genus Rothia as a potential biomarker for RR-TB noncomorbid DM.<br><br>CONCLUSIONS: Interesting findings is the community structure of microbiome in MDR-TB and RR-TB. In chronic TB such as recurrent, associated MDR-TB should attention to the findings of a small number of Actinobacteria could be a biomarker of TB which is also a determinant in patient taking combined anti-TB drugs of choice.}, }
@article {pmid34490420, year = {2021}, author = {Lymberopoulos, E and Gentili, GI and Alomari, M and Sharma, N}, title = {Topological Data Analysis Highlights Novel Geographical Signatures of the Human Gut Microbiome.}, journal = {Frontiers in artificial intelligence}, volume = {4}, number = {}, pages = {680564}, pmid = {34490420}, issn = {2624-8212}, abstract = {Background: There is growing interest in the connection between the gut microbiome and human health and disease. Conventional approaches to analyse microbiome data typically entail dimensionality reduction and assume linearity of the observed relationships, however, the microbiome is a highly complex ecosystem marked by non-linear relationships. In this study, we use topological data analysis (TDA) to explore differences and similarities between the gut microbiome across several countries. Methods: We used curated adult microbiome data at the genus level from the GMrepo database. The dataset contains OTU and demographical data of over 4,400 samples from 19 studies, spanning 12 countries. We analysed the data with tmap, an integrative framework for TDA specifically designed for stratification and enrichment analysis of population-based gut microbiome datasets. Results: We find associations between specific microbial genera and groups of countries. Specifically, both the USA and UK were significantly co-enriched with the proinflammatory genera Lachnoclostridium and Ruminiclostridium, while France and New Zealand were co-enriched with other, butyrate-producing, taxa of the order Clostridiales. Conclusion: The TDA approach demonstrates the overlap and distinctions of microbiome composition between and within countries. This yields unique insights into complex associations in the dataset, a finding not possible with conventional approaches. It highlights the potential utility of TDA as a complementary tool in microbiome research, particularly for large population-scale datasets, and suggests further analysis on the effects of diet and other regionally varying factors.}, }
@article {pmid34489882, year = {2021}, author = {Qin, J and Shi, X and Xu, J and Yuan, S and Zheng, B and Zhang, E and Huang, G and Li, G and Jiang, G and Gao, S and Tian, C and Guo, R and Fu, Z and Huang, Q and Yang, R and Zhang, W and Li, S and Wu, S}, title = {Characterization of the Genitourinary Microbiome of 1,165 Middle-Aged and Elderly Healthy Individuals.}, journal = {Frontiers in microbiology}, volume = {12}, number = {}, pages = {673969}, pmid = {34489882}, issn = {1664-302X}, abstract = {Accumulated evidence shows that complex microbial communities resides in the healthy human urinary tract and can change in urological disorders. However, there lacks a comprehensive profiling of the genitourinary microbiota in healthy cohort. Here, we performed 16S rRNA gene sequencing of midstream urine specimens from 1,172 middle-aged and elderly healthy individuals. The core microbiota included 6 dominant genera (mean relative abundance >5%), including Prevotella, Streptococcus, Lactobacillus, Gardnerella, Escherichia-Shigella, and Veillonella, and 131 low-abundance genera (0.01-5%), displaying a distinct microbiome profiles to that of host-matched gut microbiota. The composition and diversity of genitourinary microbiome (GM) were distinct between genders and may fluctuate with ages. Several urotypes were identified by the stratification of microbiome profiles, which were mainly dominated by the six most predominant genera. The prevalence of urotypes was disparate between genders, and the male sample additionally harbored other urotypes dominated by Acinetobacter, Corynebacterium, Staphylococcus, or Sphingomonas. Peptoniphilus, Ezakiella, and Porphyromonas were co-occurred and co-abundant, and they may play crucial roles as keystone genera and be associated with increased microbial diversity. Our results delineated the microbial structure and diversity landscape of the GM in healthy middle-aged and elderly adults and provided insights into the influence of gender and age to it.}, }
@article {pmid34480670, year = {2021}, author = {Vandamme, P and Peeters, C and Seth-Smith, HMB and Graf, L and Cnockaert, M and Egli, A and Goldenberger, D}, title = {Gulosibacter hominis sp. nov.: a novel human microbiome bacterium that may cause opportunistic infections.}, journal = {Antonie van Leeuwenhoek}, volume = {114}, number = {11}, pages = {1841-1854}, pmid = {34480670}, issn = {1572-9699}, mesh = {Bacterial Typing Techniques ; DNA, Bacterial/genetics ; Fatty Acids/analysis ; Humans ; *Microbiota ; Nucleic Acid Hybridization ; *Opportunistic Infections ; Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; }, abstract = {We present genomic, phylogenomic, and phenotypic taxonomic data to demonstrate that three human ear isolates represent a novel species within the genus Gulosibacter. These isolates could not be identified reliably using MALDI-TOF mass spectrometry during routine diagnostic work, but partial 16S rRNA gene sequence analysis revealed that they belonged to the genus Gulosibacter. Overall genomic relatedness indices between the draft genome sequences of the three isolates and of the type strains of established Gulosibacter species confirmed that the three isolates represented a single novel Gulosibacter species. A biochemical characterisation yielded differential tests between the novel and established Gulosibacter species, which could also be differentiated using MALDI-TOF mass spectrometry. We propose to formally classify these three isolates into Gulosibacter hominis sp. nov., with 401352-2018[ T] (= LMG 31778[ T], CCUG 74795[ T]) as the type strain. The whole-genome sequence of strain 401352-2018[ T] has a size of 2,340,181 bp and a G+C content of 62.04 mol%. A Gulosibacter pangenome analysis revealed 467 gene clusters that were exclusively present in G. hominis genomes. While these G. hominis specific gene clusters were enriched in several COG functional categories, this analysis did not reveal functions that suggested a role in the human microbiome, nor did it explain the occurrence of G. hominis in ear infections. The absence of acquired antimicrobial resistance determinants and virulence factors in the G. hominis genomes, and an analysis of publicly available 16S rRNA gene sequences and 16S rRNA amplicon sequencing data sets suggested that G. hominis is a member of the human skin microbiota that may occasionally be involved in opportunistic infections.}, }
@article {pmid34476756, year = {2021}, author = {Babino, G and Caccavale, S and Pinto, D and Trink, A and Giuliani, G and Rinaldi, F and Argenziano, G}, title = {A Randomized Double-Blind Parallel-Group Study to Evaluate the Long-Term Effects of a Medical Device Containing 0.3% Octatrienoic Acid in the Treatment of Grade III Actinic Keratosis.}, journal = {Dermatology and therapy}, volume = {11}, number = {5}, pages = {1751-1762}, pmid = {34476756}, issn = {2193-8210}, abstract = {INTRODUCTION: Actinic keratosis (AK) consists of skin lesions with a milder degree of keratinocytic atypia. It can be also referred to as "field of cancerization," which can potentially evolve to cutaneous squamous cell carcinoma (SCC). Several therapeutic options are currently available, but not all are indicated on hyperkeratotic lesions. This study aimed to test the efficacy and tolerability of a medical device containing 2,4,6-octatrienoic acid and urea for the treatment of hyperkeratotic AK lesions.<br><br>METHODS: Seventy male and female subjects with grade III AK were enrolled in this randomized double-blind parallel-group study. The product was applied once daily for three consecutive months. The primary efficacy endpoint was the reduction in the mean number of AK lesions per subject from baseline (T0) to the end of the trial (T1) and 3&#xa0;months after the end of the treatment period (T2). Therefore, clearance of target AK lesions at the end of the treatment period and local skin reaction score (LSR) versus baseline were evaluated.<br><br>RESULTS: There was a decrease of mean values from baseline to visit T2 in both treatment groups, but the decrease (versus baseline values) was more evident in the Ker&#xe0; K2 group than in the placebo group (-42.78, SD 26.53, versus -6.20, SD 31.57), and the difference was statistically significant (p&#x2009;<&#x2009;0.001). For 70 subjects (56.7%) in the Ker&#xe0; K2 group and 3 (11.54%) in the placebo group, a significant (p&#x2009;<&#x2009;0.005) partial clearance was evidenced. The product was well tolerated, and no serious adverse events were reported during the duration of the trial. Subject self-assessment of acceptability, local tolerability, and the cosmetic result was good at both T1 and T2 for both groups.<br><br>CONCLUSIONS: The medical device has demonstrated good efficacy in the reduction of visible AKs, encouraging its use.}, }
@article {pmid34471732, year = {2021}, author = {D'Huys, L and Vitale, R and Ruppeka-Rupeika, E and Goyvaerts, V and Ruckebusch, C and Hofkens, J}, title = {Assessing the Resolution of Methyltransferase-Mediated DNA Optical Mapping.}, journal = {ACS omega}, volume = {6}, number = {33}, pages = {21276-21283}, pmid = {34471732}, issn = {2470-1343}, abstract = {Interest in the human microbiome is growing and has been, for the past decade, leading to new insights into disease etiology and general human biology. Stimulated by these advances and in a parallel trend, new DNA sequencing platforms have been developed, radically expanding the possibilities in microbiome research. While DNA sequencing plays a pivotal role in this field, there are some technological hurdles that are yet to be overcome. Targeting of the 16S rRNA gene with amplicon sequencing, for instance, is frequently used for sample composition profiling due to its short sample-to-result time and low cost, which counterbalance its low resolution (genus to species level). On the other hand, more comprehensive methods, namely, whole-genome sequencing (WGS) and shallow shotgun sequencing, are capable of yielding single-gene- and functional-level resolution at a higher cost and much higher sample processing time. It goes without saying that the existing gap between these two types of approaches still calls for the development of a fast, robust, and low-cost analytical platform. In search of the latter, we investigated the taxonomic resolution of methyltransferase-mediated DNA optical mapping and found that strain-level identification can be achieved with both global and whole-genome analyses as well as using a unique identifier (UI) database. In addition, we demonstrated that UI selection in DNA optical mapping, unlike variable region selection in 16S amplicon sequencing, is not limited to any genomic location, explaining the increase in resolution. This latter aspect was highlighted by SCCmec typing in methicillin-resistant Staphylococcus aureus (MRSA) using a simulated data set. In conclusion, we propose DNA optical mapping as a method that has the potential to be highly complementary to current sequencing platforms.}, }
@article {pmid34465175, year = {2021}, author = {Zhang, Y and Thompson, KN and Branck, T and Yan Yan,  and Nguyen, LH and Franzosa, EA and Huttenhower, C}, title = {Metatranscriptomics for the Human Microbiome and Microbial Community Functional Profiling.}, journal = {Annual review of biomedical data science}, volume = {4}, number = {}, pages = {279-311}, doi = {10.1146/annurev-biodatasci-031121-103035}, pmid = {34465175}, issn = {2574-3414}, support = {K23 DK125838/DK/NIDDK NIH HHS/United States ; R39789/VAC_/Versus Arthritis/United Kingdom ; R24 DK110499/DK/NIDDK NIH HHS/United States ; C10674/A27140/CRUK_/Cancer Research UK/United Kingdom ; }, mesh = {Host Microbial Interactions ; Humans ; *Metagenomics ; *Microbiota/genetics ; Sequence Analysis, RNA ; Transcriptome ; }, abstract = {Shotgun metatranscriptomics (MTX) is an increasingly practical way to survey microbial community gene function and regulation at scale. This review begins by summarizing the motivations for community transcriptomics and the history of the field. We then explore the principles, best practices, and challenges of contemporary MTX workflows: beginning with laboratory methods for isolation and sequencing of community RNA, followed by informatics methods for quantifying RNA features, and finally statistical methods for detecting differential expression in a community context. In thesecond half of the review, we survey important biological findings from the MTX literature, drawing examples from the human microbiome, other (nonhuman) host-associated microbiomes, and the environment. Across these examples, MTX methods prove invaluable for probing microbe-microbe and host-microbe interactions, the dynamics of energy harvest and chemical cycling, and responses to environmental stresses. We conclude with a review of open challenges in the MTX field, including making assays and analyses more robust, accessible, and adaptable to new technologies; deciphering roles for millions of uncharacterized microbial transcripts; and solving applied problems such as biomarker discovery and development of microbial therapeutics.}, }
@article {pmid34461180, year = {2021}, author = {Chen, H and Ma, Y and Liu, Z and Li, J and Li, X and Yang, F and Qiu, M}, title = {Circulating microbiome DNA: An emerging paradigm for cancer liquid biopsy.}, journal = {Cancer letters}, volume = {521}, number = {}, pages = {82-87}, doi = {10.1016/j.canlet.2021.08.036}, pmid = {34461180}, issn = {1872-7980}, abstract = {Dysbiosis of the human microbiome has long been reported to be closely associated with various cancers. Accumulating studies have shown that microbial dysbiosis can accelerate tumorigenesis through tumor-promoting inflammation, DNA damage, and inducing immune evasion. Differential composition of microbiome could be novel biomarkers for cancer detection or biomarkers of successful immunotherapy. More importantly, emerging evidence demonstrates that alterations of circulating microbiome DNA (cmDNA) could serve as promising noninvasive biomarkers for cancer detection. It has been reported that distinct circulating bacterial DNA could distinguish prostate cancer, lung cancer, and melanoma patients from healthy populations. Therefore, in this review, we summarized current literature on microbial biomarkers for cancer detection and unraveled the potential of cmDNA as a promising cancer detection tool.}, }
@article {pmid34460287, year = {2021}, author = {Ancona, G and Alagna, L and Lombardi, A and Palomba, E and Castelli, V and Renisi, G and Dondossola, D and Iavarone, M and Muscatello, A and Gori, A and Bandera, A}, title = {The Interplay between Gut Microbiota and the Immune System in Liver Transplant Recipients and Its Role in Infections.}, journal = {Infection and immunity}, volume = {89}, number = {11}, pages = {e0037621}, pmid = {34460287}, issn = {1098-5522}, mesh = {Bacterial Infections/*etiology/immunology ; Drug Resistance, Multiple, Bacterial ; Dysbiosis ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/*physiology ; Host Microbial Interactions ; Humans ; Immune System/*physiology ; Liver Cirrhosis/complications/microbiology ; Liver Transplantation/*adverse effects ; Severity of Illness Index ; }, abstract = {Liver transplantation (LT) is a life-saving strategy for patients with end-stage liver disease, hepatocellular carcinoma, and acute liver failure. LT success can be hampered by several short-term and long-term complications. Among them, bacterial infections, especially those due to multidrug-resistant germs, are particularly frequent, with a prevalence between 19 and 33% in the first 100 days after transplantation. In the last decades, a number of studies have highlighted how the gut microbiota (GM) is involved in several essential functions to ensure intestinal homeostasis, becoming one of the most important virtual metabolic organs. The GM works through different axes with other organs, and the gut-liver axis is among the most relevant and investigated ones. Any alteration or disruption of the GM is defined as dysbiosis. Peculiar phenotypes of GM dysbiosis have been associated with several liver conditions and complications, such as chronic hepatitis, fatty liver disease, cirrhosis, and hepatocellular carcinoma. Moreover, there is growing evidence of the crucial role of the GM in shaping the immune response, both locally and systemically, against pathogens. This paves the way to the manipulation of the GM as a therapeutic instrument to modulate infectious risk and outcome. In this minireview, we provide an overview of the current understanding of the interplay between the gut microbiota and the immune system in liver transplant recipients and the role of the former in infections.}, }
@article {pmid34458160, year = {2021}, author = {Cho, HW and Eom, YB}, title = {Forensic Analysis of Human Microbiome in Skin and Body Fluids Based on Geographic Location.}, journal = {Frontiers in cellular and infection microbiology}, volume = {11}, number = {}, pages = {695191}, pmid = {34458160}, issn = {2235-2988}, mesh = {*Body Fluids/microbiology ; Female ; Forensic Sciences ; Geography ; Humans ; *Microbiota ; RNA, Ribosomal, 16S/genetics ; Saliva ; Skin/*microbiology ; }, abstract = {High-throughput DNA sequencing technologies have facilitated the in silico forensic analysis of human microbiome. Specific microbial species or communities obtained from the crime scene provide evidence of human contacts and their body fluids. The microbial community is influenced by geographic, ethnic, lifestyle, and environmental factors such as urbanization. An understanding of the effects of these external stressors on the human microbiome and determination of stable and changing elements are important in selecting appropriate targets for investigation. In this study, the Forensic Microbiome Database (FMD) (http://www.fmd.jcvi.org) containing the microbiome data of various locations in the human body in 35 countries was used. We focused on skin, saliva, vaginal fluid, and stool and found that the microbiome distribution differed according to the body part as well as the geographic location. In the case of skin samples, Staphylococcus species were higher than Corynebacterium species among Asians compared with Americans. Holdemanella and Fusobacterium were specific in the saliva of Koreans and Japanese populations. Lactobacillus was found in the vaginal fluids of individuals in all countries, whereas Serratia and Enterobacter were endemic to Bolivia and Congo, respectively. This study is the first attempt to collate and describe the observed variation in microbiomes from the forensic microbiome database. As additional microbiome databases are reported by studies worldwide, the diversity of the applications may exceed and expand beyond the initial identification of the host.}, }
@article {pmid34458156, year = {2021}, author = {Vork, L and Penders, J and Jalanka, J and Bojic, S and van Kuijk, SMJ and Salonen, A and de Vos, WM and Rajilic-Stojanovic, M and Weerts, ZZRM and Masclee, AAM and Pozuelo, M and Manichanh, C and Jonkers, DMAE}, title = {Does Day-to-Day Variability in Stool Consistency Link to the Fecal Microbiota Composition?.}, journal = {Frontiers in cellular and infection microbiology}, volume = {11}, number = {}, pages = {639667}, pmid = {34458156}, issn = {2235-2988}, mesh = {Feces ; *Gastrointestinal Microbiome ; Humans ; *Irritable Bowel Syndrome ; *Microbiota ; RNA, Ribosomal, 16S/genetics ; }, abstract = {INTRODUCTION: Stool consistency has been associated with fecal microbial composition. Stool consistency often varies over time, in subjects with and without gastrointestinal disorders, raising the question whether variability in the microbial composition should be considered in microbiota studies. We evaluated within-subject day-to-day variability in stool consistency and the association with the fecal microbiota in irritable bowel syndrome (IBS) and healthy subjects, over seven days.<br><br>METHODS: Twelve IBS patients and 12 healthy subjects collected fecal samples during seven consecutive days. Stool consistency was determined by the patient-reported Bristol Stool Scale (BSS) and fecal dry weight percentage. 16S rRNA V4 gene sequencing was performed and microbial richness (alpha diversity; Chao1 index, observed number of species, effective Shannon index) and microbial community structure (beta diversity; Bray-Curtis distance, generalized UniFrac, and taxa abundance on family level) were determined.<br><br>RESULTS: Linear mixed-effects models showed significant associations between stool consistency and microbial richness, but no time effect. This implies that between-subject but not within-subject variation in microbiota over time can partially be explained by variation in stool consistency. Redundancy analysis showed a significant association between stool consistency and microbial community structure, but additional linear mixed-effects models did not demonstrate a time effect on this.<br><br>CONCLUSION: This study supports an association between stool consistency and fecal microbiota, but no effect of day-to-day fluctuations in stool consistency within seven days. This consolidates the importance of considering stool consistency in gut microbiota research, though confirms the validity of single fecal sampling to represent an individual's microbiota at a given time point. NCT00775060.}, }
@article {pmid34455517, year = {2021}, author = {Li, JJ and Zhu, M and Kashyap, PC and Chia, N and Tran, NH and McWilliams, RR and Bekaii-Saab, TS and Ma, WW}, title = {The role of microbiome in pancreatic cancer.}, journal = {Cancer metastasis reviews}, volume = {40}, number = {3}, pages = {777-789}, pmid = {34455517}, issn = {1573-7233}, support = {R01 CA179243/CA/NCI NIH HHS/United States ; }, mesh = {*Carcinoma, Pancreatic Ductal/therapy ; Fecal Microbiota Transplantation ; Humans ; *Microbiota ; *Pancreatic Neoplasms/therapy ; *Probiotics/therapeutic use ; Tumor Microenvironment ; }, abstract = {Recent studies of the human microbiome have offered new insights into how the microbiome can impact cancer development and treatment. Specifically, in pancreatic ductal adenocarcinoma (PDAC), the microbiota has been shown to modulate PDAC risk, contribute to tumorigenesis, impact the tumor microenvironment, and alter treatment response. These findings provide rationale for further investigations into leveraging the microbiome to develop new strategies to diagnose and treat PDAC patients. There is growing evidence that microbiome analyses have the potential to become easily performed, non-invasive diagnostic, prognostic, and predictive biomarkers in pancreatic cancer. More excitingly, there is now emerging interest in developing interventions based on the modulation of microbiota. Fecal microbiota transplantation, probiotics, dietary changes, and antibiotics are all potential strategies to augment the efficacy of current therapeutics and reduce toxicities. While there are still challenges to overcome, this is a rapidly growing field that holds promise for translation into clinical practice and provides a new approach to improving patient outcomes.}, }
@article {pmid34451527, year = {2021}, author = {Javelle, E and Mayet, A and Million, M and Levasseur, A and Allodji, RS and Marimoutou, C and Lavagna, C and Desplans, J and Fournier, PE and Raoult, D and Texier, G}, title = {Gut Microbiota in Military International Travelers with Doxycycline Malaria Prophylaxis: Towards the Risk of a Simpson Paradox in the Human Microbiome Field.}, journal = {Pathogens (Basel, Switzerland)}, volume = {10}, number = {8}, pages = {}, pmid = {34451527}, issn = {2076-0817}, abstract = {Dysbiosis, developed upon antibiotic administration, results in loss of diversity and shifts in the abundance of gut microbes. Doxycycline is a tetracycline antibiotic widely used for malaria prophylaxis in travelers. We prospectively studied changes in the fecal microbiota of 15 French soldiers after a 4-month mission to Mali with doxycycline malaria prophylaxis, compared to changes in the microbiota of 28 soldiers deployed to Iraq and Lebanon without doxycycline. Stool samples were collected with clinical data before and after missions, and 16S rRNA sequenced on MiSeq targeting the V3-V4 region. Doxycycline exposure resulted in increased alpha-biodiversity and no significant beta-dissimilarities. It led to expansion in Bacteroides, with a reduction in Bifidobacterium and Lactobacillus, as in the group deployed without doxycycline. Doxycycline did not alter the community structure and was specifically associated with a reduction in Escherichia and expression of Rothia. Differences in the microbiota existed at baseline between military units but not within the studied groups. This group-effect highlighted the risk of a Simpson paradox in microbiome studies.}, }
@article {pmid34448860, year = {2021}, author = {Dalal, P and Sharma, D}, title = {Microbe defines the efficacy of chemotherapeutic drug: a complete paradigm.}, journal = {FEMS microbiology letters}, volume = {368}, number = {17}, pages = {}, doi = {10.1093/femsle/fnab116}, pmid = {34448860}, issn = {1574-6968}, mesh = {Drug Therapy/standards ; Humans ; *Microbiota ; *Pharmaceutical Preparations ; }, abstract = {The human body harbors a diverse microbiome that regulates host physiology and disease development. Several studies have also been reported where the human microbiome interferes with the efficacy of chemotherapeutics. Reports have also suggested the use of microbes in specific targeting and drug delivery. This review mainly focuses on the alteration in the efficacy of the drug by human microbiota. We have also discussed how the diversity in microbes can determine the therapeutic outcomes of a particular drug. The pathways involved in the alteration are also focused, with some highlights on microbes being used in cancer therapy.}, }
@article {pmid34445114, year = {2021}, author = {Kouvela, A and Zaravinos, A and Stamatopoulou, V}, title = {Adaptor Molecules Epitranscriptome Reprograms Bacterial Pathogenicity.}, journal = {International journal of molecular sciences}, volume = {22}, number = {16}, pages = {}, pmid = {34445114}, issn = {1422-0067}, support = {81344//Research Committee of the University of Patras via "C. CARATHEODORI" program/ ; }, mesh = {Anticodon/genetics ; Bacteria/*genetics/*pathogenicity ; Humans ; Nucleosides/genetics ; Protein Biosynthesis/genetics ; RNA Processing, Post-Transcriptional/genetics ; RNA, Transfer/genetics ; Transcriptome/*genetics ; Virulence/genetics ; }, abstract = {The strong decoration of tRNAs with post-transcriptional modifications provides an unprecedented adaptability of this class of non-coding RNAs leading to the regulation of bacterial growth and pathogenicity. Accumulating data indicate that tRNA post-transcriptional modifications possess a central role in both the formation of bacterial cell wall and the modulation of transcription and translation fidelity, but also in the expression of virulence factors. Evolutionary conserved modifications in tRNA nucleosides ensure the proper folding and stability redounding to a totally functional molecule. However, environmental factors including stress conditions can cause various alterations in tRNA modifications, disturbing the pathogen homeostasis. Post-transcriptional modifications adjacent to the anticodon stem-loop, for instance, have been tightly linked to bacterial infectivity. Currently, advances in high throughput methodologies have facilitated the identification and functional investigation of such tRNA modifications offering a broader pool of putative alternative molecular targets and therapeutic avenues against bacterial infections. Herein, we focus on tRNA epitranscriptome shaping regarding modifications with a key role in bacterial infectivity including opportunistic pathogens of the human microbiome.}, }
@article {pmid34442842, year = {2021}, author = {Yano, Y and Etemadi, A and Abnet, CC}, title = {Microbiome and Cancers of the Esophagus: A Review.}, journal = {Microorganisms}, volume = {9}, number = {8}, pages = {}, pmid = {34442842}, issn = {2076-2607}, support = {Intramural Research Program/CA/NCI NIH HHS/United States ; }, abstract = {Esophageal cancer (EC) is an aggressive malignant disease ranking amongst the leading causes of cancer deaths in the world. The two main histologic subtypes, esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC), have distinct geographic and temporal patterns and risk factor profiles. Despite decades of research, the factors underlying these geo-temporal patterns are still not fully understood. The human microbiome has recently been implicated in various health conditions and disease, and it is possible that the microbiome may play an important role in the etiology of EC. Although studies of the microbiome and EC are still in their early stages, we review our current understanding of the potential links between ESCC, EAC, and bacterial communities in the oral cavity and esophagus. We also provide a summary of the epidemiology of EC and highlight some key challenges and future directions.}, }
@article {pmid34437713, year = {2022}, author = {Insolia, L and Kenney, A and Chiaromonte, F and Felici, G}, title = {Simultaneous feature selection and outlier detection with optimality guarantees.}, journal = {Biometrics}, volume = {78}, number = {4}, pages = {1592-1603}, pmid = {34437713}, issn = {1541-0420}, support = {T32 LM012415/LM/NLM NIH HHS/United States ; 5T32LM012415-03/NH/NIH HHS/United States ; }, mesh = {Child ; Humans ; *Pediatric Obesity ; Algorithms ; Sample Size ; Probability ; }, abstract = {Biomedical research is increasingly data rich, with studies comprising ever growing numbers of features. The larger a study, the higher the likelihood that a substantial portion of the features may be redundant and/or contain contamination (outlying values). This poses serious challenges, which are exacerbated in cases where the sample sizes are relatively small. Effective and efficient approaches to perform sparse estimation in the presence of outliers are critical for these studies, and have received considerable attention in the last decade. We contribute to this area considering high-dimensional regressions contaminated by multiple mean-shift outliers affecting both the response and the design matrix. We develop a general framework and use mixed-integer programming to simultaneously perform feature selection and outlier detection with provably optimal guarantees. We prove theoretical properties for our approach, that is, a necessary and sufficient condition for the robustly strong oracle property, where the number of features can increase exponentially with the sample size; the optimal estimation of parameters; and the breakdown point of the resulting estimates. Moreover, we provide computationally efficient procedures to tune integer constraints and warm-start the algorithm. We show the superior performance of our proposal compared to existing heuristic methods through simulations and use it to study the relationships between childhood obesity and the human microbiome.}, }
@article {pmid34437668, year = {2021}, author = {Wilson, M and Mello, MJ and Gruppuso, PA}, title = {Antibiotics and the Human Microbiome: A Survey of Prescribing Clinicians' Knowledge and Opinions Regarding the Link between Antibiotic-Induced Dysbiosis and Immune-Mediated Disease.}, journal = {Rhode Island medical journal (2013)}, volume = {104}, number = {7}, pages = {59-63}, pmid = {34437668}, issn = {2327-2228}, mesh = {Anti-Bacterial Agents/adverse effects ; *Dysbiosis/chemically induced/drug therapy ; Humans ; *Microbiota ; Rhode Island ; }, abstract = {Altered composition or function of the human micro- biome, termed dysbiosis, has been associated with a variety of immune-mediated diseases. Antibiotic use is a well-studied cause of dysbiosis. We conducted an electronic survey of 351 antibiotic-prescribing clinicians in Rhode Island to evaluate antibiotic prescription patterns, knowledge and opinions regarding the importance of the human microbiome and its relation to antibiotics and the immune system. We found that clinicians view the health of the human microbiome as important when prescribing antibiotics; however, they do not feel well-informed or confident in their knowledge about the microbiome or its relevance to patient health. A higher level of self- reported knowledge about the microbiome was associated with increased importance placed on the microbiome and its relevance to medical practice. Our results indicate that clinicians may benefit from continuing medical education on the link between antibiotic-induced dysbiosis and immune-mediated disease.}, }
@article {pmid34430543, year = {2021}, author = {Gabaldón, T}, title = {Roles of the human microbiome in cancer.}, journal = {Hepatobiliary surgery and nutrition}, volume = {10}, number = {4}, pages = {558-560}, pmid = {34430543}, issn = {2304-3881}, }
@article {pmid34427674, year = {2021}, author = {Mejía-Caballero, A and Salas-Villagrán, VA and Jiménez-Serna, A and Farrés, A}, title = {Challenges in the production and use of probiotics as therapeuticals in cancer treatment or prevention.}, journal = {Journal of industrial microbiology &amp; biotechnology}, volume = {48}, number = {9-10}, pages = {}, pmid = {34427674}, issn = {1476-5535}, support = {//UNAM/ ; //CONACYT/ ; }, mesh = {Humans ; *Neoplasms/prevention &amp; control ; *Probiotics/therapeutic use ; }, abstract = {Probiotics were defined as microbial strains that confer health benefits to their consumers. The concept has evolved during the last 20 years, and today metabolites produced by the strains, known as postbiotics, and even dead cells, known as paraprobiotics, are closely associated to them. The isolation of commensal strains from human microbiome has led to the development of next generation probiotics. This review aims to present an overview of the developments in the area of cancer prevention and treatment, intimately related to advances in the knowledge of the microbiome role in its genesis and therapy. Strain identification and characterization, production processes, delivery strategies, and clinical evaluation are crucial to translate results into the market with solid scientific support. Examples of recent tools in isolation, strain typification, quality control, and development of new probiotic strains are described. Probiotics market and regulation were originally developed in the food sector, but these new strategies will impact the pharmaceutical and health sectors, requiring new considerations in regulatory frameworks.}, }
@article {pmid34427527, year = {2021}, author = {Ammer-Herrmenau, C and Pfisterer, N and van den Berg, T and Gavrilova, I and Amanzada, A and Singh, SK and Khalil, A and Alili, R and Belda, E and Clement, K and Abd El Wahed, A and Gady, EE and Haubrock, M and Beißbarth, T and Ellenrieder, V and Neesse, A}, title = {Comprehensive Wet-Bench and Bioinformatics Workflow for Complex Microbiota Using Oxford Nanopore Technologies.}, journal = {mSystems}, volume = {6}, number = {4}, pages = {e0075021}, pmid = {34427527}, issn = {2379-5077}, support = {404935781//Deutsche Forschungsgemeinschaft (DFG)/ ; 404935781//Deutsche Forschungsgemeinschaft (DFG)/ ; 404935781//Deutsche Forschungsgemeinschaft (DFG)/ ; }, abstract = {The advent of high-throughput sequencing techniques has recently provided an astonishing insight into the composition and function of the human microbiome. Next-generation sequencing (NGS) has become the gold standard for advanced microbiome analysis; however, 3rd generation real-time sequencing, such as Oxford Nanopore Technologies (ONT), enables rapid sequencing from several kilobases to >2 Mb with high resolution. Despite the wide availability and the enormous potential for clinical and translational applications, ONT is poorly standardized in terms of sampling and storage conditions, DNA extraction, library creation, and bioinformatic classification. Here, we present a comprehensive analysis pipeline with sampling, storage, DNA extraction, library preparation, and bioinformatic evaluation for complex microbiomes sequenced with ONT. Our findings from buccal and rectal swabs and DNA extraction experiments indicate that methods that were approved for NGS microbiome analysis cannot be simply adapted to ONT. We recommend using swabs and DNA extractions protocols with extended washing steps. Both 16S rRNA and metagenomic sequencing achieved reliable and reproducible results. Our benchmarking experiments reveal thresholds for analysis parameters that achieved excellent precision, recall, and area under the precision recall values and is superior to existing classifiers (Kraken2, Kaiju, and MetaMaps). Hence, our workflow provides an experimental and bioinformatic pipeline to perform a highly accurate analysis of complex microbial structures from buccal and rectal swabs. IMPORTANCE Advanced microbiome analysis relies on sequencing of short DNA fragments from microorganisms like bacteria, fungi, and viruses. More recently, long fragment DNA sequencing of 3rd generation sequencing has gained increasing importance and can be rapidly conducted within a few hours due to its potential real-time sequencing. However, the analysis and correct identification of the microbiome relies on a multitude of factors, such as the method of sampling, DNA extraction, sequencing, and bioinformatic analysis. Scientists have used different protocols in the past that do not allow us to compare results across different studies and research fields. Here, we provide a comprehensive workflow from DNA extraction, sequencing, and bioinformatic workflow that allows rapid and accurate analysis of human buccal and rectal swabs with reproducible protocols. This workflow can be readily applied by many scientists from various research fields that aim to use long-fragment microbiome sequencing.}, }
@article {pmid34422393, year = {2021}, author = {Grover, K and Gregory, S and Gibbs, JF and Emenaker, NJ}, title = {A discussion of the gut microbiome's development, determinants, and dysbiosis in cancers of the esophagus and stomach.}, journal = {Journal of gastrointestinal oncology}, volume = {12}, number = {Suppl 2}, pages = {S290-S300}, pmid = {34422393}, issn = {2078-6891}, abstract = {The microbiome refers to a population of microbes that colonize the skin, nasopharynx, oral cavity, gastrointestinal tract, and urogenital tract. The human microbiome consists of bacteria, archaea, fungi, viruses, and phages. Recent advances in genomic sequencing have catalyzed a deeper understanding of complex microbe-microbe and host-microbe interactions. Dysregulation of these interactions, or dysbiosis of the gastrointestinal tract, has been implicated in a growing list of pathologies including nonalcoholic fatty liver disease, cardiovascular disease, obesity, diabetes, depression, Parkinson's disease, autism, and various gastrointestinal cancers. Gastric and esophageal cancer, for example, continue to remain as two of the most common causes of cancer-related deaths worldwide, therefore there is an increased emphasis on investigating the role of dysbiosis on these cancers. In this review, we discuss the development and structure of the gut microbiome, its homeostatic and dysbiotic mechanisms, and the key microbes in esophageal and gastric carcinogenesis with a focus on bacterial biology. Further clarification of these pathways and discovery of diagnostic or therapeutic targets could have broad impacts on global subpopulations. It is important to understand the nature of the gastrointestinal tract microbiome and its potentional risk factors for dysbiosis in order to tailor its application to the individual patient and create an era of highly personalized, precision medicine.}, }
@article {pmid34419057, year = {2021}, author = {Chuzel, L and Fossa, SL and Boisvert, ML and Cajic, S and Hennig, R and Ganatra, MB and Reichl, U and Rapp, E and Taron, CH}, title = {Combining functional metagenomics and glycoanalytics to identify enzymes that facilitate structural characterization of sulfated N-glycans.}, journal = {Microbial cell factories}, volume = {20}, number = {1}, pages = {162}, pmid = {34419057}, issn = {1475-2859}, mesh = {Acetylglucosamine/*metabolism ; Enzymes/genetics/*isolation &amp; purification/*metabolism ; Kinetics ; Metagenomics/*methods ; Polysaccharides/*chemistry/*metabolism ; Sulfates/chemistry/*metabolism ; }, abstract = {BACKGROUND: Sulfate modification of N-glycans is important for several biological functions such as clearance of pituitary hormones or immunoregulation. Yet, the prevalence of this N-glycan modification and its functions remain largely unexplored. Characterization of N-glycans bearing sulfate modifications is hampered in part by a lack of enzymes that enable site-specific detection of N-glycan sulfation. In this study, we used functional metagenomic screening to identify enzymes that act upon sulfated N-acetylglucosamine (GlcNAc). Using multiplexed capillary gel electrophoresis with laser-induced fluorescence detection (xCGE-LIF) -based glycoanalysis we proved their ability to act upon GlcNAc-6-SO4 on N-glycans.<br><br>RESULTS: Our screen identified a sugar-specific sulfatase that specifically removes sulfate from GlcNAc-6-SO4 when it is in a terminal position on an N-glycan. Additionally, in the absence of calcium, this sulfatase binds to the sulfated glycan but does not remove the sulfate group, suggesting it could be used for selective isolation of sulfated N-glycans. Further, we describe isolation of a sulfate-dependent hexosaminidase that removes intact GlcNAc-6-SO4 (but not asulfated GlcNAc) from a terminal position on N-glycans. Finally, the use of these enzymes to detect the presence of sulfated N-glycans by xCGE-LIF is demonstrated.<br><br>CONCLUSION: The present study demonstrates the feasibility of using functional metagenomic screening combined with glycoanalytics to discover enzymes that act upon chemical modifications of glycans. The discovered enzymes represent new specificities that can help resolve the presence of GlcNAc-6-SO4 in N-glycan structural analyses.}, }
@article {pmid34416161, year = {2021}, author = {Li, W and Hang, S and Fang, Y and Bae, S and Zhang, Y and Zhang, M and Wang, G and McCurry, MD and Bae, M and Paik, D and Franzosa, EA and Rastinejad, F and Huttenhower, C and Yao, L and Devlin, AS and Huh, JR}, title = {A bacterial bile acid metabolite modulates Treg activity through the nuclear hormone receptor NR4A1.}, journal = {Cell host &amp; microbe}, volume = {29}, number = {9}, pages = {1366-1377.e9}, pmid = {34416161}, issn = {1934-6069}, support = {210664/Z/18/Z/WT_/Wellcome Trust/United Kingdom ; P30 DK043351/DK/NIDDK NIH HHS/United States ; R01 DK110559/DK/NIDDK NIH HHS/United States ; R35 GM128618/GM/NIGMS NIH HHS/United States ; }, mesh = {Bacteroidetes/*metabolism ; Bile Acids and Salts/*metabolism ; Cell Differentiation/physiology ; Chromatin/metabolism ; Forkhead Transcription Factors/genetics ; Humans ; Inflammatory Bowel Diseases/pathology ; Multigene Family/genetics ; Nuclear Receptor Subfamily 4, Group A, Member 1/*metabolism ; Phenanthrenes/*metabolism ; Promoter Regions, Genetic/genetics ; Signal Transduction/physiology ; T-Lymphocyte Subsets/cytology/immunology ; T-Lymphocytes, Regulatory/cytology/*immunology ; }, abstract = {Bile acids act as signaling molecules that regulate immune homeostasis, including the differentiation of CD4[+] T cells into distinct T cell subsets. The bile acid metabolite isoallolithocholic acid (isoalloLCA) enhances the differentiation of anti-inflammatory regulatory T cells (Treg cells) by facilitating the formation of a permissive chromatin structure in the promoter region of the transcription factor forkhead box P3 (Foxp3). Here, we identify gut bacteria that synthesize isoalloLCA from 3-oxolithocholic acid and uncover a gene cluster responsible for the conversion in members of the abundant human gut bacterial phylum Bacteroidetes. We also show that the nuclear hormone receptor NR4A1 is required for the effect of isoalloLCA on Treg cells. Moreover, the levels of isoalloLCA and its biosynthetic genes are significantly reduced in patients with inflammatory bowel diseases, suggesting that isoalloLCA and its bacterial producers may play a critical role in maintaining immune homeostasis in humans.}, }
@article {pmid34412621, year = {2021}, author = {Yu, ZK and Xie, RL and You, R and Liu, YP and Chen, XY and Chen, MY and Huang, PY}, title = {The role of the bacterial microbiome in the treatment of cancer.}, journal = {BMC cancer}, volume = {21}, number = {1}, pages = {934}, pmid = {34412621}, issn = {1471-2407}, support = {No.2018015//Program of Sun Yat-Sen University for Clinical Research 5010 Program(CN)/ ; No.2018029;No.201310//Program of Sun Yat-Sen University for Clinical Research 5010 Program(CN)/ ; No.81772895//National Natural Science Foundation of China/ ; No.81874134//National Natural Science Foundation of China/ ; No.2020B1111190001//Key-Area Research and Development of Guangdong Province(CN)/ ; No.2017B020226004//Guangdong Province Science and Technology Development Special Funds(CN)/ ; No.Y-JS2019-002//CSCO-JunShi Cancer Immunotherapy Clinical Research Fund(CN)/ ; }, mesh = {Animals ; Bacteria/*immunology ; *Gastrointestinal Microbiome ; Humans ; Immune System/*immunology ; Immunotherapy/*methods ; Neoplasms/immunology/microbiology/*therapy ; Probiotics/*therapeutic use ; }, abstract = {The human microbiome is defined as the microorganisms that reside in or on the human body, such as bacteria, viruses, fungi, and protozoa, and their genomes. The human microbiome participates in the modulation of human metabolism by influencing several intricate pathways. The association between specific bacteria or viruses and the efficacy of cancer treatments and the occurrence of treatment-related toxicity in cancer patients has been reported. However, the understanding of the interaction between the host microbiome and the cancer treatment response is limited, and the microbiome potentially plays a greater role in the treatment of cancer than reported to date. Here, we provide a thorough review of the potential role of the gut and locally resident bacterial microbiota in modulating responses to different cancer therapeutics to demonstrate the association between the gut or locally resident bacterial microbiota and cancer therapy. Probable mechanisms, such as metabolism, the immune response and the translocation of microbiome constituents, are discussed to promote future research into the association between the microbiome and other types of cancer. We conclude that the interaction between the host immune system and the microbiome may be the basis of the role of the microbiome in cancer therapies. Future research on the association between host immunity and the microbiome may improve the efficacy of several cancer treatments and provide insights into the cause of treatment-related side effects.}, }
@article {pmid34410636, year = {2021}, author = {Gopinath, D and Menon, RK}, title = {Increasing Reproducibility in Oral Microbiome Research.}, journal = {Methods in molecular biology (Clifton, N.J.)}, volume = {2327}, number = {}, pages = {1-15}, pmid = {34410636}, issn = {1940-6029}, mesh = {*Microbiota ; Mouth ; RNA, Ribosomal, 16S ; Reproducibility of Results ; Specimen Handling ; }, abstract = {Evidence on the role of the oral microbiome in health and disease is changing the way we understand, diagnose, and treat ailments. Numerous studies on diseases affecting the oral cavity have revealed a large amount of data that is invaluable for the advancements in diagnosing and treating these diseases. However, the clinical translation of most of these exploratory data is stalled by variable methodology between studies and non-uniform reporting of the data.Understanding the key areas that are gateways to bias in microbiome studies is imperative to overcome this challenge faced by oral microbiome research. Bias can be multifactorial and may be introduced in a microbiome research study during the formulation of the study design, sample collection and storage, or the sample processing protocols before sequencing. This chapter summarizes the recommendations from literature to eliminate bias in the microbiome research studies and to ensure the reproducibility of the microbiome research data.}, }
@article {pmid34409655, year = {2021}, author = {Huck, O and Mulhall, H and Rubin, G and Kizelnik, Z and Iyer, R and Perpich, JD and Haque, N and Cani, PD and de Vos, WM and Amar, S}, title = {Authors' Response: "Akkermansia muciniphila reduces Porphyromonas gingivalis induced inflammation and periodontal bone destruction".}, journal = {Journal of clinical periodontology}, volume = {48}, number = {11}, pages = {1493-1494}, doi = {10.1111/jcpe.13539}, pmid = {34409655}, issn = {1600-051X}, support = {RO1HL076801/HL/NHLBI NIH HHS/United States ; RO1DE014079/DE/NIDCR NIH HHS/United States ; }, mesh = {Akkermansia ; *Alveolar Bone Loss/prevention &amp; control ; Humans ; Inflammation ; *Porphyromonas gingivalis ; }, }
@article {pmid34408590, year = {2021}, author = {Mazur, M and Tomczak, H and Lodyga, M and Czajkowski, R and Żaba, R and Adamski, Z}, title = {The microbiome of the human skin and its variability in psoriasis and atopic dermatitis.}, journal = {Postepy dermatologii i alergologii}, volume = {38}, number = {2}, pages = {205-209}, pmid = {34408590}, issn = {1642-395X}, abstract = {The human organism is inhabited by very diverse microorganisms, which constitute the so-called human microbiome and are necessary for the proper functioning of the macroorganism. The correct microbiome ensures homeostasis of the body. A disturbance in its homeostasis leads to dysbiosis. Such deviations may also be related to the development of inflammatory skin diseases, including atopic dermatitis and psoriasis. This review aims to analyse the most current published data on the microbiome of the human skin and examine its role in cutaneous skin diseases, such as atopic dermatitis and psoriasis. This review was compiled by collaborating dermatologists specializing in atopic dermatitis and psoriasis. A comprehensive review of current literature was done using PubMed and limited to relevant case reports and original papers on the skin microbiome in atopic dermatitis and/or psoriasis. It has not been yet established whether changes in the microbiome are the cause or consequence of disease (atopic dermatitis/psoriasis). However, it was found that in the cases where pathological microflora predominated, an intensification of lesion severity is observed, while with clinical improvement, commensal microflora is restored. Modification of the composition of the microflora may lead to changes in the activation of the immune system and eventually to the development of inflammatory diseases. Adverse effects on the microbiome may include antibiotics, poor diet, stress and adverse environmental conditions. However, more research is needed to identify exact details and mechanisms.}, }
@article {pmid34407780, year = {2021}, author = {Kværner, AS and Birkeland, E and Bucher-Johannessen, C and Vinberg, E and Nordby, JI and Kangas, H and Bemanian, V and Ellonen, P and Botteri, E and Natvig, E and Rognes, T and Hovig, E and Lyle, R and Ambur, OH and de Vos, WM and Bultman, S and Hjartåker, A and Landberg, R and Song, M and Blix, HS and Ursin, G and Randel, KR and de Lange, T and Hoff, G and Holme, &#xd8; and Berstad, P and Rounge, TB}, title = {The CRCbiome study: a large prospective cohort study examining the role of lifestyle and the gut microbiome in colorectal cancer screening participants.}, journal = {BMC cancer}, volume = {21}, number = {1}, pages = {930}, pmid = {34407780}, issn = {1471-2407}, mesh = {Aged ; Case-Control Studies ; Colonoscopy ; Colorectal Neoplasms/*diagnosis/epidemiology/microbiology ; Early Detection of Cancer/*methods ; Female ; Follow-Up Studies ; *Gastrointestinal Microbiome ; Humans ; Incidence ; *Life Style ; Male ; Middle Aged ; Norway/epidemiology ; Occult Blood ; Prognosis ; Prospective Studies ; ROC Curve ; }, abstract = {BACKGROUND: Colorectal cancer (CRC) screening reduces CRC incidence and mortality. However, current screening methods are either hampered by invasiveness or suboptimal performance, limiting their effectiveness as primary screening methods. To aid in the development of a non-invasive screening test with improved sensitivity and specificity, we have initiated a prospective biomarker study (CRCbiome), nested within a large randomized CRC screening trial in Norway. We aim to develop a microbiome-based classification algorithm to identify advanced colorectal lesions in screening participants testing positive for an immunochemical fecal occult blood test (FIT). We will also examine interactions with host factors, diet, lifestyle and prescription drugs. The prospective nature of the study also enables the analysis of changes in the gut microbiome following the removal of precancerous lesions.<br><br>METHODS: The CRCbiome study recruits participants enrolled in the Bowel Cancer Screening in Norway (BCSN) study, a randomized trial initiated in 2012 comparing once-only sigmoidoscopy to repeated biennial FIT, where women and men aged 50-74&#x2009;years at study entry are invited to participate. Since 2017, participants randomized to FIT screening with a positive test result have been invited to join the CRCbiome study. Self-reported diet, lifestyle and demographic data are collected prior to colonoscopy after the positive FIT-test (baseline). Screening data, including colonoscopy findings are obtained from the BCSN database. Fecal samples for gut microbiome analyses are collected both before and 2 and 12&#x2009;months after colonoscopy. Samples are analyzed using metagenome sequencing, with taxonomy profiles, and gene and pathway content as primary measures. CRCbiome data will also be linked to national registries to obtain information on prescription histories and cancer relevant outcomes occurring during the 10&#x2009;year follow-up period.<br><br>DISCUSSION: The CRCbiome study will increase our understanding of how the gut microbiome, in combination with lifestyle and environmental factors, influences the early stages of colorectal carcinogenesis. This knowledge will be crucial to develop microbiome-based screening tools for CRC. By evaluating biomarker performance in a screening setting, using samples from the target population, the generalizability of the findings to future screening cohorts is likely to be high.<br><br>TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01538550 .}, }
@article {pmid34402650, year = {2021}, author = {Adriaenssens, EM}, title = {Phage Diversity in the Human Gut Microbiome: a Taxonomist's Perspective.}, journal = {mSystems}, volume = {6}, number = {4}, pages = {e0079921}, pmid = {34402650}, issn = {2379-5077}, support = {BBS/E/F/000PR10353/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; BBS/E/F/000PR10356/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; BB/R012490/1//UKRI | Biotechnology and Biological Sciences Research Council (BBSRC)/ ; }, abstract = {Bacteriophages (phages) have been known for over a century, but only in the last 2 decades have we really come to appreciate how abundant and diverse they are. With that realization, research groups across the globe have shown the importance of phage-based processes in a myriad of environments, including the global oceans and soils, and as part of the human microbiome. Through advances in sequencing technology, genomics, and bioinformatics, we know that the morphological diversity of bacteriophages originally used for taxonomy is eclipsed by their genomic diversity. Because we currently do not have a complete taxonomic framework or naming scheme to describe this diversity, crucial information from virome and microbiome studies is being lost. In this commentary, I will discuss recent advances in taxonomy and its importance for studies of the microbiome with examples of the human gut phageome and make recommendations for future analyses.}, }
@article {pmid34402617, year = {2021}, author = {Esvap, E and Ulgen, KO}, title = {Advances in Genome-Scale Metabolic Modeling toward Microbial Community Analysis of the Human Microbiome.}, journal = {ACS synthetic biology}, volume = {10}, number = {9}, pages = {2121-2137}, doi = {10.1021/acssynbio.1c00140}, pmid = {34402617}, issn = {2161-5063}, mesh = {Gastrointestinal Microbiome ; *Genomics ; Humans ; Inflammatory Bowel Diseases/microbiology/pathology ; Machine Learning ; Metabolic Networks and Pathways/genetics ; Microbiota/*genetics/physiology ; Models, Biological ; Parkinson Disease/microbiology/pathology ; Precision Medicine ; }, abstract = {A genome-scale metabolic model (GEM) represents metabolic pathways of an organism in a mathematical form and can be built using biochemistry and genome annotation data. GEMs are invaluable for understanding organisms since they analyze the metabolic capabilities and behaviors quantitatively and can predict phenotypes. The development of high-throughput data collection techniques led to an immense increase in omics data such as metagenomics, which expand our knowledge on the human microbiome, but this also created a need for systematic analysis of these data. In recent years, GEMs have also been reconstructed for microbial species, including human gut microbiota, and methods for the analysis of microbial communities have been developed to examine the interaction between the organisms or the host. The purpose of this review is to provide a comprehensive guide for the applications of GEMs in microbial community analysis. Starting with GEM repositories, automatic GEM reconstruction tools, and quality control of models, this review will give insights into microbe-microbe and microbe-host interaction predictions and optimization of microbial community models. Recent studies that utilize microbial GEMs and personalized models to infer the influence of microbiota on human diseases such as inflammatory bowel diseases (IBD) or Parkinson's disease are exemplified. Being powerful system biology tools for both species-level and community-level analysis of microbes, GEMs integrated with omics data and machine learning techniques will be indispensable for studying the microbiome and their effects on human physiology as well as for deciphering the mechanisms behind human diseases.}, }
@article {pmid34400408, year = {2021}, author = {Knippel, RJ and Drewes, JL and Sears, CL}, title = {The Cancer Microbiome: Recent Highlights and Knowledge Gaps.}, journal = {Cancer discovery}, volume = {11}, number = {10}, pages = {2378-2395}, pmid = {34400408}, issn = {2159-8290}, support = {R00 CA230192/CA/NCI NIH HHS/United States ; R01 CA196845/CA/NCI NIH HHS/United States ; C10674/A27140/CRUK_/Cancer Research UK/United Kingdom ; }, mesh = {*Cell Transformation, Neoplastic ; Humans ; *Microbiota ; *Neoplasms ; }, abstract = {Knowledge of the human microbiome, which is likely a critical factor in the initiation, progression, and prognosis of multiple forms of cancer, is rapidly expanding. In this review, we focus on recent investigations to discern putative, causative microbial species and the microbiome composition and structure currently associated with procarcinogenesis and tumorigenesis at select body sites. We specifically highlight forms of cancer, gastrointestinal and nongastrointestinal, that have significant bacterial associations and well-defined experimental evidence with the aim of generating directions for future experimental and translational investigations to develop a clearer understanding of the multifaceted mechanisms by which microbiota affect cancer formation. SIGNIFICANCE: Emerging and, for some cancers, strong experimental and translational data support the contribution of the microbiome to cancer biology and disease progression. Disrupting microbiome features and pathways contributing to cancer may provide new approaches to improving cancer outcomes in patients.}, }
@article {pmid34399524, year = {2021}, author = {van Dongen, KCW and Linkens, AMA and Wetzels, SMW and Wouters, K and Vanmierlo, T and van de Waarenburg, MPH and Scheijen, JLJM and de Vos, WM and Belzer, C and Schalkwijk, CG}, title = {Dietary advanced glycation endproducts (AGEs) increase their concentration in plasma and tissues, result in inflammation and modulate gut microbial composition in mice; evidence for reversibility.}, journal = {Food research international (Ottawa, Ont.)}, volume = {147}, number = {}, pages = {110547}, doi = {10.1016/j.foodres.2021.110547}, pmid = {34399524}, issn = {1873-7145}, mesh = {Animals ; Diet ; *Gastrointestinal Microbiome ; *Glycation End Products, Advanced ; Inflammation ; Mice ; Mice, Inbred C57BL ; }, abstract = {SCOPE: Dietary advanced glycation endproducts (AGEs) are associated with negative biological effects, possibly due to accumulation in plasma and tissues and through modulation of inflammation and gut microbiota. Whether these biological consequences are reversible by limiting dietary AGE intake is unknown.<br><br>METHODS AND RESULTS: Young healthy C57BL/6 mice were fed a standard chow (n&#xa0;=&#xa0;10) or a baked chow high AGE-diet (n&#xa0;=&#xa0;10) (~1.8-6.9 fold increased protein-bound N&#x3b5;-(carboxymethyl)lysine (CML), N&#x3b5;-(1-carboxyethyl)lysine (CEL), and N&#x3b4;-(5-hydro-5-methyl-4-imidazolon-2-yl)-ornithine (MG-H1)) for 10&#xa0;weeks or a switch diet with baked chow for 5&#xa0;weeks followed by 5&#xa0;weeks of standard chow (n&#xa0;=&#xa0;10). We assessed accumulation of AGEs in plasma, kidney, and liver and measured inflammatory markers and gut microbial composition. After 10&#xa0;weeks of baked chow, a substantial panel of AGEs were increased in plasma, liver, and kidney. These increases were normalized after the switch diet. The inflammatory z-score increased after the baked chow diet. Gut microbial composition differed significantly between groups, with enriched Dubosiella spp. dominating these alterations.<br><br>CONCLUSION: A high AGE-diet led to an increase of AGEs in plasma, kidney, and liver and to more inflammation and modification of the gut microbiota. These effects were reversed or discontinued by a diet lower in AGEs.}, }
@article {pmid34387406, year = {2021}, author = {Alenius, H and Sinkko, H and Moitinho-Silva, L and Rodriguez, E and Broderick, C and Alexander, H and Reiger, M and Hjelmsø, MH and Fyhrquist, N and Olah, P and Bryce, P and Smith, C and Koning, F and Eyerich, K and Greco, D and van den Bogaard, EH and Neumann, AU and Traidl-Hoffmann, C and Homey, B and Flohr, C and Bønnelykke, K and Stokholm, J and Weidinger, S}, title = {The power and potential of BIOMAP to elucidate host-microbiome interplay in skin inflammatory diseases.}, journal = {Experimental dermatology}, volume = {30}, number = {10}, pages = {1517-1531}, doi = {10.1111/exd.14446}, pmid = {34387406}, issn = {1600-0625}, mesh = {Dermatitis, Atopic/*immunology/*microbiology ; Humans ; Microbiota/*immunology ; Psoriasis/*immunology/*microbiology ; Skin/*immunology/*microbiology ; }, abstract = {The two most common chronic inflammatory skin diseases are atopic dermatitis (AD) and psoriasis. The underpinnings of the remarkable degree of clinical heterogeneity of AD and psoriasis are poorly understood and, as a consequence, disease onset and progression are unpredictable and the optimal type and time point for intervention are as yet unknown. The BIOMAP project is the first IMI (Innovative Medicines Initiative) project dedicated to investigating the causes and mechanisms of AD and psoriasis and to identify potential biomarkers responsible for the variation in disease outcome. The consortium includes 7 large pharmaceutical companies and 25 non-industry partners including academia. Since there is mounting evidence supporting an important role for microbial exposures and our microbiota as factors mediating immune polarization and AD and psoriasis pathogenesis, an entire work package is dedicated to the investigation of skin and gut microbiome linked to AD or psoriasis. The large collaborative BIOMAP project will enable the integration of patient cohorts, data and knowledge in unprecedented proportions. The project has a unique opportunity with a potential to bridge and fill the gaps between current problems and solutions. This review highlights the power and potential of the BIOMAP project in the investigation of microbe-host interplay in AD and psoriasis.}, }
@article {pmid34386513, year = {2021}, author = {Jana, UK and Kango, N and Pletschke, B}, title = {Hemicellulose-Derived Oligosaccharides: Emerging Prebiotics in Disease Alleviation.}, journal = {Frontiers in nutrition}, volume = {8}, number = {}, pages = {670817}, pmid = {34386513}, issn = {2296-861X}, abstract = {The gut microbiota in the human body is an important component that plays a pivotal role in the ability of the host to prevent diseases and recover from these diseases. If the human microbiome changes for any reason, it affects the overall functioning of the host. Healthy and vigorous gut microbiota require dietary fiber supplementation. Recently, oligosaccharides have been found to play a significant role in the modulation of microbiota. Several such oligosaccharides, i.e., xylooligosaccharides (XOS), mannooligosaccharides (MOS), and arabino-xylooligosaccharides (AXOS), are derived from hemicellulosic macromolecules such as xylan, mannan, and arabino-xylan, respectively. These oligosaccharides serve as substrates for the probiotic production of health-promoting substances (short-chain fatty acids, branched chain amino acids etc.), which confer a variety of health benefits, including the prevention of some dreaded diseases. Among hemicellulose-derived oligosaccharides (HDOs), XOS have been largely explored, whereas, studies on MOS and AXOS are currently underway. HDOs, upon ingestion, help reduce morbidities by lowering populations of harmful or pathogenic bacteria. The ATP-binding cassette (ABC) transporters are mainly utilized for the uptake of oligosaccharides in probiotics. Butyrate generated by the selective fermentation of oligosaccharides, along with other short-chain fatty acids, reduces gut inflammation. Overall, oligosaccharides derived from hemicelluloses show a similar potential as conventional prebiotics and can be supplemented as functional foods. This review summarizes the role of HDOs in the alleviation of autoimmune diseases (inflammatory bowel disease, Crohn's disease), diabetes, urinary tract infection, cardiovascular diseases, and antimicrobial resistance (AMR) through the modulation of the gut microbiota. The mechanism of oligosaccharide utilization and disease mitigation is also explained.}, }
@article {pmid34381207, year = {2021}, author = {Fremin, BJ and Nicolaou, C and Bhatt, AS}, title = {Simultaneous ribosome profiling of hundreds of microbes from the human microbiome.}, journal = {Nature protocols}, volume = {16}, number = {10}, pages = {4676-4691}, pmid = {34381207}, issn = {1750-2799}, support = {R01 AI148623/AI/NIAID NIH HHS/United States ; U24 AG021886/AG/NIA NIH HHS/United States ; R01 AI143757/AI/NIAID NIH HHS/United States ; P50 AG047366/AG/NIA NIH HHS/United States ; P30 CA124435/CA/NCI NIH HHS/United States ; P30 AG047366//U.S. Department of Health &amp; Human Services | National Institutes of Health (NIH)/ ; P30 AG066515/AG/NIA NIH HHS/United States ; }, mesh = {Humans ; *Ribosomes/metabolism/genetics ; *Feces/microbiology ; *Microbiota/genetics ; Metagenomics/methods ; Metagenome ; Bacteria/genetics/classification ; High-Throughput Nucleotide Sequencing/methods ; Gastrointestinal Microbiome/genetics ; Ribosome Profiling ; }, abstract = {Ribosome profiling enables sequencing of ribosome-bound fragments of RNA, revealing which transcripts are being translated as well as the position of ribosomes along mRNAs. Although ribosome profiling has been applied to cultured bacterial isolates, its application to uncultured, mixed communities has been challenging. We present MetaRibo-Seq, a protocol that enables the application of ribosome profiling directly to the human fecal microbiome. MetaRibo-Seq is a benchmarked method that includes several modifications to existing ribosome profiling protocols, specifically addressing challenges involving fecal sample storage, purity and input requirements. We also provide a computational workflow to quality control and trim reads, de novo assemble a reference metagenome with metagenomic reads, align MetaRibo-Seq reads to the reference, and assess MetaRibo-Seq library quality (https://github.com/bhattlab/bhattlab_workflows/tree/master/metariboseq). This MetaRibo-Seq protocol enables researchers in standard molecular biology laboratories to study translation in the fecal microbiome in ~5 d.}, }
@article {pmid34379050, year = {2022}, author = {Ahmed, E and Hens, K}, title = {Microbiome in Precision Psychiatry: An Overview of the Ethical Challenges Regarding Microbiome Big Data and Microbiome-Based Interventions.}, journal = {AJOB neuroscience}, volume = {13}, number = {4}, pages = {270-286}, doi = {10.1080/21507740.2021.1958096}, pmid = {34379050}, issn = {2150-7759}, mesh = {Humans ; Big Data ; *Psychiatry ; *Mental Disorders/therapy ; *Microbiota/genetics ; Mental Health ; }, abstract = {There has been a spurt in both fundamental and translational research that examines the underlying mechanisms of the human microbiome in psychiatric disorders. The personalized and dynamic features of the human microbiome suggest the potential of its manipulation for precision psychiatry in ways to improve mental health and avoid disease. However, findings in the field of microbiome also raise philosophical and ethical questions. From a philosophical point of view, they may yet be another attempt at providing a biological cause for phenomena that ultimately cannot be so easily localized. From an ethical point of view, it is relevant that the human gut microbiome comprises data on the individual's lifestyle, disease history, previous medications, and mental health. Massive datasets of microbiome sequences are collected to facilitate comparative studies to identify specific links between the microbiome and mental health. Although this emerging research domain may show promise for psychiatric patients, it is surrounded by ethical challenges regarding patient privacy, health risks, effects on personal identity, and concerns about responsibility. This narrative overview displays the roles and advances of microbiome research in psychiatry and discusses the philosophical and ethical implications of microbiome big data and microbiome-based interventions for psychiatric patients. We also investigate whether these issues are really "new," or "old wine in new bottles."}, }
@article {pmid34376656, year = {2021}, author = {Bui, TPN and Mannerås-Holm, L and Puschmann, R and Wu, H and Troise, AD and Nijsse, B and Boeren, S and Bäckhed, F and Fiedler, D and deVos, WM}, title = {Conversion of dietary inositol into propionate and acetate by commensal Anaerostipes associates with host health.}, journal = {Nature communications}, volume = {12}, number = {1}, pages = {4798}, pmid = {34376656}, issn = {2041-1723}, mesh = {Acetates/*metabolism ; Animals ; Clostridiales/classification/*metabolism/physiology ; Diet ; Feces/microbiology ; Host Microbial Interactions ; Humans ; Inositol/*metabolism ; Intestines/*chemistry/microbiology ; Magnetic Resonance Spectroscopy/methods ; Male ; Mice, Inbred C57BL ; Phytic Acid/metabolism ; Propionates/*metabolism ; Tandem Mass Spectrometry/methods ; Mice ; }, abstract = {We describe the anaerobic conversion of inositol stereoisomers to propionate and acetate by the abundant intestinal genus Anaerostipes. A inositol pathway was elucidated by nuclear magnetic resonance using [[13]C]-inositols, mass spectrometry and proteogenomic analyses in A. rhamnosivorans, identifying 3-oxoacid CoA transferase as a key enzyme involved in both 3-oxopropionyl-CoA and propionate formation. This pathway also allowed conversion of phytate-derived inositol into propionate as shown with [[13]C]-phytate in fecal samples amended with A. rhamnosivorans. Metabolic and (meta)genomic analyses explained the adaptation of Anaerostipes spp. to inositol-containing substrates and identified a propionate-production gene cluster to be inversely associated with metabolic biomarkers in (pre)diabetes cohorts. Co-administration of myo-inositol with live A. rhamnosivorans in western-diet fed mice reduced fasting-glucose levels comparing to heat-killed A. rhamnosivorans after 6-weeks treatment. Altogether, these data suggest a potential beneficial role for intestinal Anaerostipes spp. in promoting host health.}, }
@article {pmid34372590, year = {2021}, author = {Skurnik, M and Jaakkola, S and Mattinen, L and von Ossowski, L and Nawaz, A and Pajunen, MI and Happonen, LJ}, title = {Bacteriophages fEV-1 and fD1 Infect Yersinia pestis.}, journal = {Viruses}, volume = {13}, number = {7}, pages = {}, pmid = {34372590}, issn = {1999-4915}, mesh = {Bacteriophages/*genetics/*physiology/ultrastructure ; Finland ; *Genome, Viral ; Host Specificity ; Microscopy, Electron, Transmission ; *Proteome ; Sewage ; Yersinia pestis/classification/*virology ; }, abstract = {Bacteriophages vB_YpeM_fEV-1 (fEV-1) and vB_YpeM_fD1 (fD1) were isolated from incoming sewage water samples in Turku, Finland, using Yersinia pestis strains EV76 and KIM D27 as enrichment hosts, respectively. Genomic analysis and transmission electron microscopy established that fEV-1 is a novel type of dwarf myovirus, while fD1 is a T4-like myovirus. The genome sizes are 38 and 167 kb, respectively. To date, the morphology and genome sequences of some dwarf myoviruses have been described; however, a proteome characterization such as the one presented here, has currently been lacking for this group of viruses. Notably, fEV-1 is the first dwarf myovirus described for Y. pestis. The host range of fEV-1 was restricted strictly to Y. pestis strains, while that of fD1 also included other members of Enterobacterales such as Escherichia coli and Yersinia pseudotuberculosis. In this study, we present the life cycles, genomes, and proteomes of two Yersinia myoviruses, fEV-1 and fD1.}, }
@article {pmid34368762, year = {2021}, author = {Puca, P and Petito, V and Laterza, L and Lopetuso, LR and Neri, M and Del Chierico, F and Boskoski, I and Gasbarrini, A and Scaldaferri, F}, title = {Bariatric procedures and microbiota: patient selection and outcome prediction.}, journal = {Therapeutic advances in gastrointestinal endoscopy}, volume = {14}, number = {}, pages = {26317745211014746}, pmid = {34368762}, issn = {2631-7745}, abstract = {Obesity is a major health issue throughout the world and bariatric surgery plays a key role in its management and treatment. The role of microbiota in determining the pathogenesis of obesity has been widely studied, while its role in determining the outcome of bariatric surgery is an emerging issue that will be an outcome in near future studies. Studies on mice first showed the key role of microbiota in determining obesity, highlighting the fat mass increase in mice transplanted with microbiota from fat individuals, as well as the different microbiota composition between mice undergone to low-fat or high-fat diets. This led to characterize the asset of microbiota composition in obesity: increased abundance of Firmicutes, reduced abundance of Bacteroidetes and other taxonomical features. Variations on the composition of gut microbiome have been detected in patients undergone to diet and/or bariatric surgery procedures. Patients undergone to restricting diets showed lower level of trimethylamine N-oxide and other metabolites strictly associated to microbiome, as well as patients treated with bariatric surgery showed, after the procedure, changes in the relative abundance of Bacteroidetes, Firmicutes and other phyla with a role in the pathogenesis of obesity. Eventually, studies have been led about the effects that the modification of microbiota could have on obesity itself, mainly focusing on elements like fecal microbiota transplantation and probiotics such as inulin. This series of studies and considerations represent the first step in order to select patients eligible to bariatric surgery and to predict their outcome.}, }
@article {pmid34368008, year = {2021}, author = {Josephs-Spaulding, J and Krogh, TJ and Rettig, HC and Lyng, M and Chkonia, M and Waschina, S and Graspeuntner, S and Rupp, J and Møller-Jensen, J and Kaleta, C}, title = {Recurrent Urinary Tract Infections: Unraveling the Complicated Environment of Uncomplicated rUTIs.}, journal = {Frontiers in cellular and infection microbiology}, volume = {11}, number = {}, pages = {562525}, pmid = {34368008}, issn = {2235-2988}, mesh = {Anti-Bacterial Agents/therapeutic use ; Humans ; Inflammation/drug therapy ; Urinary Bladder ; *Urinary Tract Infections ; }, abstract = {Urinary tract infections (UTIs) are frequent in humans, affecting the upper and lower urinary tract. Present diagnosis relies on the positive culture of uropathogenic bacteria from urine and clinical markers of inflammation of the urinary tract. The bladder is constantly challenged by adverse environmental stimuli which influence urinary tract physiology, contributing to a dysbiotic environment. Simultaneously, pathogens are primed by environmental stressors such as antibiotics, favoring recurrent UTIs (rUTIs), resulting in chronic illness. Due to different confounders for UTI onset, a greater understanding of the fundamental environmental mechanisms and microbial ecology of the human urinary tract is required. Such advancements could promote the tandem translation of bench and computational studies for precision treatments and clinical management of UTIs. Therefore, there is an urgent need to understand the ecological interactions of the human urogenital microbial communities which precede rUTIs. This review aims to outline the mechanistic aspects of rUTI ecology underlying dysbiosis between both the human microbiome and host physiology which predisposes humans to rUTIs. By assessing the applications of next generation and systems level methods, we also recommend novel approaches to elucidate the systemic consequences of rUTIs which requires an integrated approach for successful treatment. To this end, we will provide an outlook towards the so-called 'uncomplicated environment of UTIs', a holistic and systems view that applies ecological principles to define patient-specific UTIs. This perspective illustrates the need to withdraw from traditional reductionist perspectives in infection biology and instead, a move towards a systems-view revolving around patient-specific pathophysiology during UTIs.}, }
@article {pmid34367159, year = {2021}, author = {de Jong, E and Lauzon-Joset, JF and Leffler, J and Serralha, M and Larcombe, AN and Christophersen, CT and Holt, PG and Strickland, DH and Bosco, A}, title = {IRF7-Associated Immunophenotypes Have Dichotomous Responses to Virus/Allergen Coexposure and OM-85-Induced Reprogramming.}, journal = {Frontiers in immunology}, volume = {12}, number = {}, pages = {699633}, pmid = {34367159}, issn = {1664-3224}, mesh = {Allergens/*immunology ; Animals ; Asthma/etiology/*immunology ; Cardiovirus Infections/*immunology ; Cell Extracts/*pharmacology ; Immunophenotyping ; Interferon Regulatory Factor-7/*immunology ; Male ; Rats ; }, abstract = {High risk for virus-induced asthma exacerbations in children is associated with an IRF7lo immunophenotype, but the underlying mechanisms are unclear. Here, we applied a Systems Biology approach to an animal model comprising rat strains manifesting high (BN) versus low susceptibility (PVG) to experimental asthma, induced by virus/allergen coexposure, to elucidate the mechanism(s)-of-action of the high-risk asthma immunophenotype. We also investigated potential risk mitigation via pretreatment with the immune training agent OM-85. Virus/allergen coexposure in low-risk PVG rats resulted in rapid and transient airways inflammation alongside IRF7 gene network formation. In contrast, responses in high-risk BN rats were characterized by severe airways eosinophilia and exaggerated proinflammatory responses that failed to resolve, and complete absence of IRF7 gene networks. OM-85 had more profound effects in high-risk BN rats, inducing immune-related gene expression changes in lung at baseline and reducing exaggerated airway inflammatory responses to virus/allergen coexposure. In low-risk PVG rats, OM-85 boosted IRF7 gene networks in the lung but did not alter baseline gene expression or cellular influx. Distinct IRF7-associated asthma risk immunophenotypes have dichotomous responses to virus/allergen coexposure and respond differentially to OM-85 pretreatment. Extrapolating to humans, our findings suggest that the beneficial effects OM-85 pretreatment may preferentially target those in high-risk subgroups.}, }
@article {pmid34367134, year = {2021}, author = {Hetemäki, I and Jian, C and Laakso, S and Mäkitie, O and Pajari, AM and de Vos, WM and Arstila, TP and Salonen, A}, title = {Fecal Bacteria Implicated in Biofilm Production Are Enriched and Associate to Gastrointestinal Symptoms in Patients With APECED - A Pilot Study.}, journal = {Frontiers in immunology}, volume = {12}, number = {}, pages = {668219}, pmid = {34367134}, issn = {1664-3224}, mesh = {Adult ; Aged ; Antibodies, Fungal/metabolism ; Bacteria/genetics/*growth &amp; development/immunology/metabolism ; Biofilms/*growth &amp; development ; Case-Control Studies ; Dysbiosis ; Feces/*microbiology ; Female ; Finland ; Gastrointestinal Diseases/diagnosis/immunology/metabolism/*microbiology ; *Gastrointestinal Microbiome ; Genetic Predisposition to Disease ; Host-Pathogen Interactions ; Humans ; Immunoglobulin G/metabolism ; Intestines/*microbiology ; Lipopolysaccharides/metabolism ; Male ; Metagenome ; Middle Aged ; *Mutation ; Pilot Projects ; Polyendocrinopathies, Autoimmune/complications/diagnosis/genetics/immunology ; Saccharomyces cerevisiae/genetics/immunology ; Transcription Factors/*genetics ; Young Adult ; AIRE Protein ; }, abstract = {BACKGROUNDS AND AIMS: APECED is a rare autoimmune disease caused by mutations in the Autoimmune Regulator gene. A significant proportion of patients also have gastrointestinal symptoms, including malabsorption, chronic diarrhea, and obstipation. The pathological background of the gastrointestinal symptoms remains incompletely understood and involves multiple factors, with autoimmunity being the most common underlying cause. Patients with APECED have increased immune responses against gut commensals. Our objective was to evaluate whether the intestinal microbiota composition, predicted functions or fungal abundance differ between Finnish patients with APECED and healthy controls, and whether these associate to the patients' clinical phenotype and gastrointestinal symptoms.<br><br>METHODS: DNA was isolated from fecal samples from 15 patients with APECED (median age 46.4 years) together with 15 samples from body mass index matched healthy controls. DNA samples were subjected to analysis of the gut microbiota using 16S rRNA gene amplicon sequencing, imputed metagenomics using the PICRUSt2 algorithm, and quantitative PCR for fungi. Extensive correlations of the microbiota with patient characteristics were determined.<br><br>RESULTS: Analysis of gut microbiota indicated that both alpha- and beta-diversity were altered in patients with APECED compared to healthy controls. The fraction of Faecalibacterium was reduced in patients with APECED while that of Atopobium spp. and several gram-negative genera previously implicated in biofilm formation, e.g. Veillonella, Prevotella, Megasphaera and Heamophilus, were increased in parallel to lipopolysaccharide (LPS) synthesis in imputed metagenomics. The differences in gut microbiota were linked to patient characteristics, especially the presence of anti-Saccharomyces cerevisiae antibodies (ASCA) and severity of gastrointestinal symptoms.<br><br>CONCLUSIONS: Gut microbiota of patients with APECED is altered and enriched with predominantly gram-negative bacterial taxa that may promote biofilm formation and lead to increased exposure to LPS in the patients. The most pronounced alterations in the microbiota were associated with more severe gastrointestinal symptoms.}, }
@article {pmid34365823, year = {2021}, author = {Thiele-Bruhn, S}, title = {The role of soils in provision of genetic, medicinal and biochemical resources.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {376}, number = {1834}, pages = {20200183}, pmid = {34365823}, issn = {1471-2970}, mesh = {*Biodiversity ; Conservation of Natural Resources ; *Ecosystem ; Humans ; *Microbiota ; Mycorrhizae ; Soil/*chemistry ; *Soil Microbiology ; }, abstract = {Intact, 'healthy' soils provide indispensable ecosystem services that largely depend on the biotic activity. Soil health is connected with human health, yet, knowledge of the underlying soil functioning remains incomplete. This review highlights selected services, i.e. (i) soil as a genetic resource and hotspot of biodiversity, forming the basis for providing (ii) biochemical resources and (iii) medicinal services and goods. Soils harbour an unrivalled biodiversity of organisms, especially microorganisms. Some of the abilities of autochthonous microorganisms and their relevant enzymes serve (i) to improve natural soil functions and in particular plant growth, e.g. through beneficial plant growth-promoting, symbiotic and mycorrhizal microorganisms, (ii) to act as biopesticides, (iii) to facilitate biodegradation of pollutants for soil bioremediation and (iv) to yield enzymes or chemicals for industrial use. Soils also exert direct effects on human health. Contact with soil enriches the human microbiome, affords protection against allergies and promotes emotional well-being. Medicinally relevant are soil substrates such as loams, clays and various minerals with curative effects as well as pharmaceutically active organic chemicals like antibiotics that are formed by soil microorganisms. By contrast, irritating minerals, soil dust inhalation and misguided soil ingestion may adversely affect humans. This article is part of the theme issue 'The role of soils in delivering Nature's Contributions to People.}, }
@article {pmid34365651, year = {2021}, author = {Dwivedi, M and Powali, S and Rastogi, S and Singh, A and Gupta, DK}, title = {Microbial community in human gut: a therapeutic prospect and implication in health and diseases.}, journal = {Letters in applied microbiology}, volume = {73}, number = {5}, pages = {553-568}, doi = {10.1111/lam.13549}, pmid = {34365651}, issn = {1472-765X}, mesh = {*Gastrointestinal Microbiome ; Humans ; *Microbiota ; *Probiotics/therapeutic use ; }, abstract = {The interest in the working and functionality of the human gut microbiome has increased drastically over the years. Though the existence of gut microbes has long been speculated for long over the last few decades, a lot of research has sprung up in studying and understanding the role of gut microbes in the human digestive tract. The microbes present in the gut are highly instrumental in maintaining the metabolism in the body. Further research is going on in this field to understand how gut microbes can be employed as potential sources of novel therapeutics; moreover, probiotics have also elucidated their significant place in this direction. As regards the clinical perspective, microbes can be engineered to afford defence mechanisms while interacting with foreign pathogenic bodies. More investigations in this field may assist us to evaluate and understand how these cells communicate with human cells and promote immune interactions. Here we elaborate on the possible implication of human gut microbiota into the immune system as well as explore the probiotics in the various human ailments. Comprehensive information on the human gut microbiome at the same platform may contribute effectively to our understanding of the human microbiome and possible mechanisms of associated human diseases.}, }
@article {pmid34364710, year = {2021}, author = {Kanangat, S and Skaljic, I}, title = {Microbiome analysis, the immune response and transplantation in the era of next generation sequencing.}, journal = {Human immunology}, volume = {82}, number = {11}, pages = {883-901}, doi = {10.1016/j.humimm.2021.07.009}, pmid = {34364710}, issn = {1879-1166}, mesh = {Computational Biology ; Dysbiosis/*diagnosis/immunology/microbiology ; Graft Rejection/immunology/prevention &amp; control ; HLA Antigens/genetics ; *High-Throughput Nucleotide Sequencing ; Histocompatibility Testing/methods ; Host Microbial Interactions/genetics/*immunology ; Humans ; Microbiota/*genetics/immunology ; Sequence Analysis, DNA/methods ; Sequence Analysis, RNA/methods ; Transplantation, Homologous/adverse effects ; }, abstract = {The human gastrointestinal tract, skin and mucosal surfaces are inhabited by a complex system of bacteria, viruses, fungi, archaea, protists, and eukaryotic parasites with predominance of bacteria and bacterial viruses (bacteriophages). Collectively these microbes form the microbiota of the microecosystem of humans. Recent advancement in technologies for nucleic acid isolation from various environmental samples, feces and body secretions and advancements in shotgun throughput massive parallel DNA and RNA sequencing along with 16S ribosomal gene sequencing have unraveled the identity of otherwise unknown microbial entities constituting the human microecosystem. The improved transcriptome analysis, technological developments in biochemical analytical methods and availability of complex bioinformatics tools have allowed us to begin to understand the metabolome of the microbiome and the biochemical pathways and potential signal transduction pathways in human cells in response to microbial infections and their products. Also, developments in human whole genome sequencing, targeted gene sequencing of histocompatibility genes and other immune response associated genes by Next Generation Sequencing (NGS) have allowed us to have a better conceptualization of immune responses, and alloimmune responses. These modern technologies have enabled us to dive into the intricate relationship between commensal symbiotic and pathogenic microbiome and immune system. For the most part, the commensal symbiotic microbiota helps to maintain normal immune homeostasis besides providing healthy nutrients, facilitating digestion, and protecting the skin, mucosal and intestinal barriers. However, changes in diets, administration of therapeutic agents like antibiotics, chemotherapeutic agents, immunosuppressants etc. along with certain host factors including human histocompatibility antigens may alter the microbial ecosystem balance by causing changes in microbial constituents, hierarchy of microbial species and even dysbiosis. Such alterations may cause immune dysregulation, breach of barrier protection and lead to immunopathogenesis rather than immune homeostasis. The effects of human microbiome on immunity, health and disease are currently under intense research with cutting edge technologies in molecular biology, biochemistry, and bioinformatics along with tremendous ability to characterize immune response at single cell level. This review will discuss the contemporary status on human microbiome immune system interactions and their potential effects on health, immune homeostasis and allograft transplantation.}, }
@article {pmid34361885, year = {2021}, author = {Kim, JC and Park, MJ and Park, S and Lee, ES}, title = {Alteration of the Fecal but Not Salivary Microbiome in Patients with Behçet's Disease According to Disease Activity Shift.}, journal = {Microorganisms}, volume = {9}, number = {7}, pages = {}, pmid = {34361885}, issn = {2076-2607}, abstract = {The human microbiome plays an important role in various diseases, including Behçet's disease (BD). However, the effects of disease activity and covariates influencing the microbial composition have not yet been investigated. Therefore, we investigated the fecal and salivary microbiomes of BD patients compared to those of recurrent aphthous ulcer (RAU) patients, as well as dietary habit-matched healthy controls (HCs) selected from immediate family members using 16S rRNA gene sequencing. The fecal microbiome alpha diversity of BD patients was not different from that of their matched HCs, although it was higher than that of unrelated HCs and decreased in BD patients with disease activity. A tendency toward clustering in the beta diversity of the fecal microbiome was observed between the active BD patients and their matched HCs. Active BD patients had a significantly higher abundance of fecal Bacteroides uniformis than their matched HCs and patients with the disease in an inactive state (p = 0.038). The abundance of salivary Rothia mucilaginosa group was higher in BD patients than in RAUs patients. BD patients with uveitis had different abundances of various taxa, compared to those without uveitis. Our results showed an association of fecal microbiome composition with BD disease activity and symptoms, suggesting the possible role of the gut microbiome in BD pathogenesis.}, }
@article {pmid34361691, year = {2021}, author = {Puebla-Barragan, S and Watson, E and van der Veer, C and Chmiel, JA and Carr, C and Burton, JP and Sumarah, M and Kort, R and Reid, G}, title = {Interstrain Variability of Human Vaginal Lactobacillus crispatus for Metabolism of Biogenic Amines and Antimicrobial Activity against Urogenital Pathogens.}, journal = {Molecules (Basel, Switzerland)}, volume = {26}, number = {15}, pages = {}, pmid = {34361691}, issn = {1420-3049}, support = {692895//Consejo Nacional de Ciencia y Tecnolog&#xed;a/ ; }, mesh = {Anti-Infective Agents/*metabolism ; Biogenic Amines/*metabolism ; Candida albicans/metabolism ; Dysbiosis/metabolism/microbiology ; Enterococcus faecium/metabolism ; Escherichia coli/metabolism ; Female ; Female Urogenital Diseases/*metabolism/*microbiology ; Genomics/methods ; Humans ; Lactobacillus crispatus/classification/genetics/*metabolism ; Metabolome ; Metabolomics/methods ; *Microbiota ; Phylogeny ; Prevotella/metabolism ; Probiotics/metabolism ; Vagina/*microbiology ; }, abstract = {Lactobacillus crispatus is the dominant species in the vagina of many women. With the potential for strains of this species to be used as a probiotic to help prevent and treat dysbiosis, we investigated isolates from vaginal swabs with Lactobacillus-dominated and a dysbiotic microbiota. A comparative genome analysis led to the identification of metabolic pathways for synthesis and degradation of three major biogenic amines in most strains. However, targeted metabolomic analysis of the production and degradation of biogenic amines showed that certain strains have either the ability to produce or to degrade these compounds. Notably, six strains produced cadaverine, one produced putrescine, and two produced tyramine. These biogenic amines are known to raise vaginal pH, cause malodour, and make the environment more favourable to vaginal pathogens. In vitro experiments confirmed that strains isolated from women with a dysbiotic vaginal microbiota have higher antimicrobial effects against the common urogenital pathogens Escherichia coli and Enterococcus faecium. The results indicate that not all L. crispatus vaginal strains appear suitable for probiotic application and the basis for selection should not be only the overall composition of the vaginal microbiota of the host from which they came, but specific biochemical and genetic traits.}, }
@article {pmid34358008, year = {2021}, author = {Chow, EWL and Pang, LM and Wang, Y}, title = {From Jekyll to Hyde: The Yeast-Hyphal Transition of Candida albicans.}, journal = {Pathogens (Basel, Switzerland)}, volume = {10}, number = {7}, pages = {}, pmid = {34358008}, issn = {2076-0817}, support = {NMRC/OFIRG/0072/2018 and NMRC/OFIRG/0055/2019//National Medical Research Council of Singapore/ ; NRF2019-NRF-ISF003-3039//National Research Foundation of Singapore/ ; }, abstract = {Candida albicans is a major fungal pathogen of humans, accounting for 15% of nosocomial infections with an estimated attributable mortality of 47%. C. albicans is usually a benign member of the human microbiome in healthy people. Under constant exposure to highly dynamic environmental cues in diverse host niches, C. albicans has successfully evolved to adapt to both commensal and pathogenic lifestyles. The ability of C. albicans to undergo a reversible morphological transition from yeast to filamentous forms is a well-established virulent trait. Over the past few decades, a significant amount of research has been carried out to understand the underlying regulatory mechanisms, signaling pathways, and transcription factors that govern the C. albicans yeast-to-hyphal transition. This review will summarize our current understanding of well-elucidated signal transduction pathways that activate C. albicans hyphal morphogenesis in response to various environmental cues and the cell cycle machinery involved in the subsequent regulation and maintenance of hyphal morphogenesis.}, }
@article {pmid34355132, year = {2021}, author = {Barton, W and Cronin, O and Garcia-Perez, I and Whiston, R and Holmes, E and Woods, T and Molloy, CB and Molloy, MG and Shanahan, F and Cotter, PD and O'Sullivan, O}, title = {The effects of sustained fitness improvement on the gut microbiome: A longitudinal, repeated measures case-study approach.}, journal = {Translational sports medicine}, volume = {4}, number = {2}, pages = {174-192}, pmid = {34355132}, issn = {2573-8488}, support = {CDF-2017-10-032/DH_/Department of Health/United Kingdom ; PDF-2012-05-456/DH_/Department of Health/United Kingdom ; }, abstract = {The athlete gut microbiome differs from that of non-athletes in its composition and metabolic function. Short-term fitness improvement in sedentary adults does not replicate the microbiome characteristics of athletes. The objective of this study was to investigate whether sustained fitness improvement leads to pronounced alterations in the gut microbiome. This was achieved using a repeated-measures, case-study approach that examined the gut microbiome of two initially unfit volunteers undertaking progressive exercise training over a 6-month period. Samples were collected every two weeks, and microbiome, metabolome, diet, body composition, and cardiorespiratory fitness data were recorded. Training culminated in both participants completing their respective goals (a marathon or Olympic-distance triathlon) with improved body composition and fitness parameters. Increases in gut microbiota α-diversity occurred with sustained training and fluctuations occurred in response to training events (eg, injury, illness, and training peaks). Participants' BMI reduced during the study and was significantly associated with increased urinary measurements of N-methyl nicotinate and hippurate, and decreased phenylacetylglutamine. These results suggest that sustained fitness improvements support alterations to gut microbiota and physiologically-relevant metabolites. This study provides longitudinal analysis of the gut microbiome response to real-world events during progressive fitness training, including intercurrent illness and injury.}, }
@article {pmid34350192, year = {2021}, author = {De Vincentis, A and Santonico, M and Del Chierico, F and Altomare, A and Marigliano, B and Laudisio, A and Reddel, S and Grasso, S and Zompanti, A and Pennazza, G and Putignani, L and Guarino, MPL and Cicala, M and Antonelli Incalzi, R}, title = {Gut Microbiota and Related Electronic Multisensorial System Changes in Subjects With Symptomatic Uncomplicated Diverticular Disease Undergoing Rifaximin Therapy.}, journal = {Frontiers in medicine}, volume = {8}, number = {}, pages = {655474}, pmid = {34350192}, issn = {2296-858X}, abstract = {Background: Intestinal dysbiosis might play a pathogenetic role in subjects with symptomatic uncomplicated diverticular disease (SUDD), but the effect of rifaximin therapy has been scantly explored with regard to gut microbiota variations in patients with SUDD. Aims: To verify to which extent rifaximin treatment affects the gut microbiota and whether an electronic multisensorial assessment of stools and breath has the potential for detecting these changes. Methods: Breath and stool samples were collected from consecutive patients with SUDD before and after a 7 days' therapy with rifaximin. Stool microbiota was assessed, and the electronic multisensorial assessment was carried out by means of the BIONOTE electronic (e-)tongue in stools and (e-)nose in breath. Results: Forty-three subjects (female 60%, median age 66 years) were included, and 20 (47%) reported clinical improvement after rifaximin therapy. Alpha and beta diversity of stool microbiota did not significantly change after treatment, while a significant variation of selected taxa was shown (i.e., Citrobacter, Coprococcus, Anaerotruncus, Blautia, Eggerthella lenta, Dehalobacterium, SMB53, and Haemophilus parainfluenzae). Overall, the electronic multisensorial system suboptimally mirrored microbiota changes, but it was able to efficiently predict patients' clinical improvement after rifaximin with accuracies ranging from 0.81 to 0.98. Conclusions: In patients with SUDD, rifaximin administration is associated with significant variation of selected taxa. While inaccurate in predicting gut microbiota change, an electronic multisensorial system, made up of e-tongue and e-nose, was able to predict clinical improvement, thus potentially qualifying as an easy and cheap tool to forecast subjects taking most likely benefit from rifaximin therapy.}, }
@article {pmid34348558, year = {2022}, author = {Bajinka, O and Simbilyabo, L and Tan, Y and Jabang, J and Saleem, SA}, title = {Lung-brain axis.}, journal = {Critical reviews in microbiology}, volume = {48}, number = {3}, pages = {257-269}, doi = {10.1080/1040841X.2021.1960483}, pmid = {34348558}, issn = {1549-7828}, mesh = {Animals ; Brain ; *Gastrointestinal Microbiome ; Lung ; *Neurodegenerative Diseases ; Prospective Studies ; *Respiratory Tract Infections ; }, abstract = {The appreciation of human microbiome is gaining strong grounds in biomedical research. In addition to gut-brain axis, is the lung-brain axis, which is hypothesised to link pulmonary microbes to neurodegenerative disorders and behavioural changes. There is a need for analysis based on emerging studies to map out the prospects for lung-brain axis. In this review, relevant English literature and researches in the field of 'lung-brain axis' is reported. We recommend all the highlighted prospective studies to be integrated with an interdisciplinary approach. This might require conceptual research approaches based on physiology and pathophysiology. Multimodal aspects should include experimental animal units, while exploring the research gaps and making reference to the already existing human data. The overall microbiome medicine is gaining more ground. Aetiological paths and experimental recommendations as per prospective studies in this review will be an important guideline to develop effective treatments for any lung induced neurodegenerative diseases. An in-depth knowledge of the bi-directional communication between host and microbiome in the lung could help treatment to respiratory infections, alleviate stress, anxiety and enhanced neurological effects. The timely prevention and treatment of neurodegenerative diseases requires paradigm shift of the aetiology and more innovative experimentation.Impact statementThe overall microbiome medicine is gaining more ground. An in-depth knowledge of the bi-directional communication between host and microbiome in the lung could confer treatment to respiratory infections, alleviate stress, anxiety and enhanced neurological effects. Based on this review, we recommend all the highlighted prospective studies to be integrated and be given an interdisciplinary approach. This might require conceptual research approaches based on physiology and pathophysiology. Multimodal aspects should include experimental animal units; while exploring the research gaps and making reference to the already existing human data.}, }
@article {pmid34348151, year = {2021}, author = {Kieft, K and Breister, AM and Huss, P and Linz, AM and Zanetakos, E and Zhou, Z and Rahlff, J and Esser, SP and Probst, AJ and Raman, S and Roux, S and Anantharaman, K}, title = {Virus-associated organosulfur metabolism in human and environmental systems.}, journal = {Cell reports}, volume = {36}, number = {5}, pages = {109471}, doi = {10.1016/j.celrep.2021.109471}, pmid = {34348151}, issn = {2211-1247}, mesh = {*Environment ; Gastrointestinal Microbiome ; Genes, Viral ; Genetic Variation ; Genomics ; Humans ; Metabolic Networks and Pathways/genetics ; Microbiota ; Organic Chemicals/*metabolism ; Phylogeny ; Recombination, Genetic/genetics ; Sulfides/metabolism ; Sulfur/*metabolism ; Viruses/genetics/*metabolism ; }, abstract = {Viruses influence the fate of nutrients and human health by killing microorganisms and altering metabolic processes. Organosulfur metabolism and biologically derived hydrogen sulfide play dynamic roles in manifestation of diseases, infrastructure degradation, and essential biological processes. Although microbial organosulfur metabolism is well studied, the role of viruses in organosulfur metabolism is unknown. Here, we report the discovery of 39 gene families involved in organosulfur metabolism encoded by 3,749 viruses from diverse ecosystems, including human microbiomes. The viruses infect organisms from all three domains of life. Six gene families encode for enzymes that degrade organosulfur compounds into sulfide, whereas others manipulate organosulfur compounds and may influence sulfide production. We show that viral metabolic genes encode key enzymatic domains, are translated into protein, and are maintained after recombination, and sulfide provides a fitness advantage to viruses. Our results reveal viruses as drivers of organosulfur metabolism with important implications for human and environmental health.}, }
@article {pmid34348027, year = {2021}, author = {Britton, GJ and Faith, JJ}, title = {Causative Microbes in Host-Microbiome Interactions.}, journal = {Annual review of microbiology}, volume = {75}, number = {}, pages = {223-242}, doi = {10.1146/annurev-micro-041321-042402}, pmid = {34348027}, issn = {1545-3251}, mesh = {Animals ; Host Microbial Interactions ; *Microbiota ; Symbiosis ; }, abstract = {Despite identification of numerous associations between microbiomes and diseases, the complexity of the human microbiome has hindered identification of individual species and strains that are causative in host phenotype or disease. Uncovering causative microbes is vital to fully understand disease processes and to harness the potential therapeutic benefits of microbiota manipulation. Developments in sequencing technology, animal models, and bacterial culturing have facilitated the discovery of specific microbes that impact the host and are beginning to advance the characterization of host-microbiome interaction mechanisms. We summarize the historical and contemporary experimental approaches taken to uncover microbes from the microbiota that affect host biology and describe examples of commensals that have specific effects on the immune system, inflammation, and metabolism. There is still much to learn, and we lay out challenges faced by the field and suggest potential remedies for common pitfalls encountered in the hunt for causative commensal microbes.}, }
@article {pmid34342530, year = {2021}, author = {Kuthyar, S and Reese, AT}, title = {Variation in Microbial Exposure at the Human-Animal Interface and the Implications for Microbiome-Mediated Health Outcome.}, journal = {mSystems}, volume = {6}, number = {4}, pages = {e0056721}, pmid = {34342530}, issn = {2379-5077}, support = {T32 GM127235/GM/NIGMS NIH HHS/United States ; }, abstract = {The human gut microbiome varies between populations, largely reflecting ecological differences. One ecological variable that is rarely considered but may contribute substantially to microbiome variation is the multifaceted nature of human-animal interfaces. We present the hypothesis that different interactions with animals contribute to shaping the human microbiome globally. We utilize a One Health framework to explore how changes in microbial exposure from human-animal interfaces shape the microbiome and, in turn, contribute to differential human health across populations, focusing on commensal and pathogen exposure, changes in colonization resistance and immune system training, and the potential for other functional shifts. Although human-animal interfaces are known to underlie human health and particularly infectious disease disparities, since their impact on the human microbiome remains woefully understudied, we propose foci for future research. We believe it will be crucial to understand this critical aspect of biology and its impacts on human health around the globe.}, }
@article {pmid34335499, year = {2021}, author = {Peterson, D and Bonham, KS and Rowland, S and Pattanayak, CW and ,  and Klepac-Ceraj, V}, title = {Comparative Analysis of 16S rRNA Gene and Metagenome Sequencing in Pediatric Gut Microbiomes.}, journal = {Frontiers in microbiology}, volume = {12}, number = {}, pages = {670336}, pmid = {34335499}, issn = {1664-302X}, abstract = {The colonization of the human gut microbiome begins at birth, and over time, these microbial communities become increasingly complex. Most of what we currently know about the human microbiome, especially in early stages of development, was described using culture-independent sequencing methods that allow us to identify the taxonomic composition of microbial communities using genomic techniques, such as amplicon or shotgun metagenomic sequencing. Each method has distinct tradeoffs, but there has not been a direct comparison of the utility of these methods in stool samples from very young children, which have different features than those of adults. We compared the effects of profiling the human infant gut microbiome with 16S rRNA amplicon vs. shotgun metagenomic sequencing techniques in 338 fecal samples; younger than 15, 15-30, and older than 30 months of age. We demonstrate that observed changes in alpha-diversity and beta-diversity with age occur to similar extents using both profiling methods. We also show that 16S rRNA profiling identified a larger number of genera and we find several genera that are missed or underrepresented by each profiling method. We present the link between alpha diversity and shotgun metagenomic sequencing depth for children of different ages. These findings provide a guide for selecting an appropriate method and sequencing depth for the three studied age groups.}, }
@article {pmid34332502, year = {2021}, author = {Moeller, AH}, title = {Genomic Expansions in the Human Gut Microbiome.}, journal = {Genome biology and evolution}, volume = {13}, number = {7}, pages = {}, pmid = {34332502}, issn = {1759-6653}, support = {R35 GM138284/GM/NIGMS NIH HHS/United States ; }, mesh = {*Gastrointestinal Microbiome/genetics ; Genome, Bacterial ; Genomics ; Humans ; Metagenome ; *Microbiota ; }, abstract = {Bacteria inhabiting the human body vary in genome size by over an order of magnitude, but the processes that generate this diversity are poorly understood. Here, we show that evolutionary forces drive divergence in genome size between bacterial lineages in the gut and their closest relatives in other body sites. Analyses of thousands of reference bacterial isolate genomes and metagenome-assembled genomes from the human microbiome indicated that transitions into the gut from other body sites have promoted genomic expansions, whereas the opposite transitions have promoted genomic contractions. Bacterial genomes in the gut are on average ∼127 kb larger than their closest congeneric relatives from other body sites. Moreover, genome size and relative abundance are positively associated within the gut but negatively associated at other body sites. These results indicate that the gut microbiome promotes expansions of bacterial genomes relative to other body sites.}, }
@article {pmid34331994, year = {2021}, author = {Suojalehto, H and Ndika, J and Lindström, I and Airaksinen, L and Karisola, P and Alenius, H}, title = {Endotyping asthma related to 3 different work exposures.}, journal = {The Journal of allergy and clinical immunology}, volume = {148}, number = {4}, pages = {1072-1080}, doi = {10.1016/j.jaci.2021.07.019}, pmid = {34331994}, issn = {1097-6825}, mesh = {Adult ; Air Pollutants, Occupational/*adverse effects ; Asthma, Occupational/blood/*genetics/immunology/physiopathology ; Biomarkers ; Biopsy ; Cell Movement ; Cytokines/blood ; Flour/*adverse effects ; Gene Expression Profiling ; Humans ; Immunoglobulin E/blood ; Inhalation Exposure/*adverse effects ; Isocyanates/*adverse effects ; Leukocytes/immunology ; Male ; Middle Aged ; Nasal Mucosa/pathology ; Nitric Oxide/metabolism ; Occupational Exposure/*adverse effects ; Respiratory Function Tests ; *Welding ; }, abstract = {BACKGROUND: Work exposures play a significant role in adult-onset asthma, but the mechanisms of work-related asthma are not fully elucidated.<br><br>OBJECTIVE: We aimed to reveal the molecular mechanisms of work-related asthma associated with exposure to flour (flour asthma), isocyanate (isocyanate asthma), or welding fumes (welding asthma) and identify potential biomarkers that distinguish these groups from each other.<br><br>METHODS: We used a combination of clinical tests, transcriptomic analysis, and associated pathway analyses to investigate the underlying disease mechanisms of the blood immune cells and the airway epithelium of 61 men.<br><br>RESULTS: Compared with the healthy controls, the welding asthma patients had more differentially expressed genes than the flour asthma and isocyanate asthma patients, both in the airway epithelia and in the blood immune cells. In the airway epithelia, active inflammation was detected only in welding asthma patients. In contrast, many differentially expressed genes were detected in blood cells in all 3 asthma groups. Disease-related immune functions in blood cells, including leukocyte migration and inflammatory responses, and decreased expression of upstream cytokines such as TNF and IFN-&#x3b3; were suppressed in all the asthma groups. In transcriptome-phenotype correlations, hyperresponsiveness (R &#x223c; |0.6|) had the highest clinical relevance and was associated with a set of exposure group-specific genes. Finally, biomarker subsets of only 5&#xa0;genes&#xa0;specifically distinguished each of the asthma exposure groups.<br><br>CONCLUSIONS: This study provides novel data on the molecular mechanisms underlying work-related asthma. We identified a set of 5 promising biomarkers in asthma related to flour, isocyanate, and welding fume exposure to be tested and clinically validated in future studies.}, }
@article {pmid34330476, year = {2021}, author = {Varsha, KK and Maheshwari, AP and Nampoothiri, KM}, title = {Accomplishment of probiotics in human health pertaining to immunoregulation and disease control.}, journal = {Clinical nutrition ESPEN}, volume = {44}, number = {}, pages = {26-37}, doi = {10.1016/j.clnesp.2021.06.020}, pmid = {34330476}, issn = {2405-4577}, mesh = {Dietary Supplements ; *Gastrointestinal Microbiome ; Humans ; *Intestinal Diseases ; *Probiotics ; }, abstract = {It is a well-established fact that the microbiome harboring the human body plays a critical role in maintaining human health and can influence treatments against various ailments. Human microbiome-based research contemplates the possibility of selecting and administering specific commensal bacterial strains to modulate the gut microbiota to attain favorable outcomes to the therapies. Consumption of probiotics and probiotic-based dietary supplements as functional foods has been a promising treatment strategy against various diseases. Clinical studies demonstrate that probiotic administration alters gut microbiota composition and instigates immune modulation in the host. The benefits of probiotics are reported to be strain-specific and depend on the host's baseline immune competence. This review explores the role of probiotics in alleviating symptoms of allergy, cancer, cardio vascular (CV) diseases, diabetes mellitus (DM), bowel diseases (IBD and IBS), periodontal disease, diseases affecting liver and kidney, neuroinflammatory diseases, and viral infections. Also, it surveyed the broad spectrum bioactive compounds produced by probiotics and possible mechanisms that trigger the immune system.}, }
@article {pmid34329771, year = {2021}, author = {Avis, T and Wilson, FX and Khan, N and Mason, CS and Powell, DJ}, title = {Targeted microbiome-sparing antibiotics.}, journal = {Drug discovery today}, volume = {26}, number = {9}, pages = {2198-2203}, doi = {10.1016/j.drudis.2021.07.016}, pmid = {34329771}, issn = {1878-5832}, support = {/WT_/Wellcome Trust/United Kingdom ; }, mesh = {Anti-Bacterial Agents/*therapeutic use ; Bacterial Infections/diagnosis/drug therapy/microbiology ; Dysbiosis/*prevention &amp; control ; Humans ; Microbiota/*drug effects ; }, abstract = {A factor in our inability to meet the challenge of clinical antibiotic resistance has been the low productivity of research and development (R&amp;D) efforts, with only incremental improvements on existing broad-spectrum classes coming into clinical use recently. The disappointing returns from this approach have focussed attention on narrower-spectrum antibiotics; such new agents are directed against the pathogen of relevance with the additional benefit of preserving the human microbiome(s). Our knowledge of the gut microbiome and its contribution to health homeostasis increases yearly and suggests that broad-spectrum treatments incur health costs beyond the initial infection. Improved diagnostics, antibiotic stewardship, and the crucial role of the gut microbiome in health indicate targeted agents as a more viable approach for future antibiotic R&amp;D.}, }
@article {pmid34329170, year = {2022}, author = {Ko, YJ and Kim, S and Pan, CH and Park, K}, title = {Identification of Functional Microbial Modules Through Network-Based Analysis of Meta-Microbial Features Using Matrix Factorization.}, journal = {IEEE/ACM transactions on computational biology and bioinformatics}, volume = {19}, number = {5}, pages = {2851-2862}, doi = {10.1109/TCBB.2021.3100893}, pmid = {34329170}, issn = {1557-9964}, mesh = {*Algorithms ; Humans ; *Microbiota/genetics ; }, abstract = {As the microbiome is composed of a variety of microbial interactions, it is imperative in microbiome research to identify a microbial sub-community that collectively conducts a specific function. However, current methodologies have been highly limited to analyzing conditional abundance changes of individual microorganisms without considering group-wise collective microbial features. To overcome this limitation, we developed a network-based method using nonnegative matrix factorization (NMF) to identify functional meta-microbial features (MMFs) that, as a group, better discriminate specific environmental conditions of samples using microbiome data. As proof of concept, large-scale human microbiome data collected from different body sites were used to identify body site-specific MMFs by applying NMF. The statistical test for MMFs led us to identify highly discriminative MMFs on sample classes, called synergistic MMFs (SYMMFs). Finally, we constructed a SYMMF-based microbial interaction network (SYMMF-net) by integrating all of the SYMMF information. Network analysis revealed core microbial modules closely related to critical sample properties. Similar results were also found when the method was applied to various disease-associated microbiome data. The developed method interprets high-dimensional microbiome data by identifying functional microbial modules on sample properties and intuitively representing their systematic relationships via a microbial network.}, }
@article {pmid34319607, year = {2021}, author = {Briana, DD and Papaevangelou, V and Malamitsi-Puchner, A}, title = {The jury is still out on the existence of a placental microbiome.}, journal = {Acta paediatrica (Oslo, Norway : 1992)}, volume = {110}, number = {11}, pages = {2958-2963}, doi = {10.1111/apa.16048}, pmid = {34319607}, issn = {1651-2227}, mesh = {Bacteria ; Female ; Fetus ; Humans ; *Infertility ; *Microbiota ; Placenta ; Pregnancy ; }, abstract = {The human microbiome is crucial for regulating normal development, but the exact point when it is established remains unknown. A sterile placenta was traditionally considered a prerequisite for a healthy pregnancy, but studies have revealed that the placenta harbours microbial communities, even under normal conditions. However, reports have failed to provide evidence for the consistent presence of bacteria in the normal human placenta, challenging the in utero colonisation hypothesis. This mini review examines our understanding of the potential placental microbial colonisation in normal healthy pregnancies. This may impact the metabolic and immune functions of the growing foetus and have long-term consequences.}, }
@article {pmid34319583, year = {2022}, author = {Aronson, MR and Ali Akbari Ghavimi, S and Gehret, PM and Jacobs, IN and Gottardi, R}, title = {Drug-Eluting Endotracheal Tubes for Preventing Bacterial Inflammation in Subglottic Stenosis.}, journal = {The Laryngoscope}, volume = {132}, number = {7}, pages = {1356-1363}, doi = {10.1002/lary.29769}, pmid = {34319583}, issn = {1531-4995}, mesh = {Anti-Bacterial Agents/pharmacology/therapeutic use ; Bacteria ; Constriction, Pathologic/complications ; Humans ; Inflammation ; Intubation, Intratracheal/adverse effects ; *Laryngostenosis/etiology/prevention &amp; control ; }, abstract = {OBJECTIVES/HYPOTHESIS: Subglottic stenosis (SGS) results from dysregulated extracellular matrix deposition by laryngotracheal fibroblasts causing scar tissue formation following intubation. Recent work has highlighted a relationship between this inflammatory state and imbalances in the upper airway microbiome. Herein, we engineer novel drug-eluting endotracheal (ET) tubes to deliver a model antimicrobial peptide Lasioglossin-III (Lasio) for the local modulation of the microbiome during intubation.<br><br>STUDY DESIGN: Controlled in vitro study.<br><br>METHODS: ET tubes were coated with a water-in-oil (w/o) emulsion of Lasio in poly(d,l-lactide-co-glycolide) (PLGA) by dipping thrice. Peptide release was quantified over 2&#x2009;weeks via fluorometric peptide assays. The antibacterial activity was tested against airway microbes (Staphylococcus epidermidis, Streptococcus pneumoniae, and pooled human microbiome samples) by placing Lasio/PLGA-coated tubes and appropriate controls in 48 well plates with diluted bacteria. Bacterial inhibition and tube adhesion were tested by measuring optical density and colony formation after tube culture, respectively. Biocompatibility was tested against laryngotracheal fibroblasts and lung epithelial cells.<br><br>RESULTS: We achieved a homogeneous coating of ET tubes with Lasio in a PLGA matrix that yields a prolonged, linear release over 1&#x2009;week (typical timeframe before the ET tube is changed). We observed significant antibacterial activity against S. epidermidis, S. pneumoniae, and human microbiome samples, and prevention of bacterial adherence to the tube. Additionally, the released Lasio did not cause any cytotoxicity toward laryngotracheal fibroblasts or lung epithelial cells in vitro.<br><br>CONCLUSION: Overall, we demonstrate the design of an effective-eluting ET tube to modulate upper-airway bacterial infections during intubation which could be deployed to help prevent SGS.<br><br>LEVEL OF EVIDENCE: NA Laryngoscope, 132:1356-1363, 2022.}, }
@article {pmid34315165, year = {2022}, author = {Bernard, R and Fazili, I and Rajagopala, SV and Das, SR and Hiremath, G}, title = {Association between Oral Microbiome and Esophageal Diseases: A State-of-the-Art Review.}, journal = {Digestive diseases (Basel, Switzerland)}, volume = {40}, number = {3}, pages = {345-354}, pmid = {34315165}, issn = {1421-9875}, support = {K12 HD087023/HD/NICHD NIH HHS/United States ; R21 AI149262/AI/NIAID NIH HHS/United States ; T32 HD060554/HD/NICHD NIH HHS/United States ; P30 AI110527/AI/NIAID NIH HHS/United States ; U19 AI095227/AI/NIAID NIH HHS/United States ; R01 HL146401/HL/NHLBI NIH HHS/United States ; R21 AI142321/AI/NIAID NIH HHS/United States ; R21 AI154016/AI/NIAID NIH HHS/United States ; }, mesh = {*Barrett Esophagus/pathology ; *Esophageal Diseases/complications ; *Esophageal Neoplasms/pathology ; Humans ; *Microbiota ; *Precancerous Conditions/pathology ; }, abstract = {BACKGROUND: Esophageal conditions result in significant morbidity and mortality worldwide. There is growing enthusiasm for discerning the role of microbiome in esophageal diseases. Conceivably, the focus has been on examining the role of local microbiome in esophageal diseases although this is somewhat limited by the invasive approach required to sample the esophageal tissue. Given the ease of sampling the oral cavity combined with the advances in genomic techniques, there is immense interest in discovering the role of the oral microbiome in esophageal conditions.<br><br>SUMMARY: In this review, we aim to discuss the current evidence highlighting the association between the oral microbiome and esophageal diseases. In particular, we have focused on summarizing the alterations in oral microbiome associated with malignant, premalignant, and benign esophageal cancers, inflammatory and infectious conditions, and esophageal dysmotility diseases. Identifying alterations in the oral microbiome is a key to advancing our understanding of the etiopathogenesis and progression of esophageal diseases, promoting novel diagnostics, and laying the foundation for personalized treatment approaches.<br><br>KEY MESSAGES: Further studies are needed to unravel the mechanisms by which the oral microbiome influences the development and progression of esophageal diseases, as well as to investigate whether alterations in the oral microbiome can impact the natural history of various esophageal diseases.}, }
@article {pmid34314593, year = {2021}, author = {Heinken, A and Basile, A and Hertel, J and Thinnes, C and Thiele, I}, title = {Genome-Scale Metabolic Modeling of the Human Microbiome in the Era of Personalized Medicine.}, journal = {Annual review of microbiology}, volume = {75}, number = {}, pages = {199-222}, doi = {10.1146/annurev-micro-060221-012134}, pmid = {34314593}, issn = {1545-3251}, mesh = {*Gastrointestinal Microbiome ; Humans ; *Microbiota ; Precision Medicine ; }, abstract = {The human microbiome plays an important role in human health and disease. Meta-omics analyses provide indispensable data for linking changes in microbiome composition and function to disease etiology. Yet, the lack of a mechanistic understanding of, e.g., microbiome-metabolome links hampers the translation of these findings into effective, novel therapeutics. Here, we propose metabolic modeling of microbial communities through constraint-based reconstruction and analysis (COBRA) as a complementary approach to meta-omics analyses. First, we highlight the importance of microbial metabolism in cardiometabolic diseases, inflammatory bowel disease, colorectal cancer, Alzheimer disease, and Parkinson disease. Next, we demonstrate that microbial community modeling can stratify patients and controls, mechanistically link microbes with fecal metabolites altered in disease, and identify host pathways affected by the microbiome. Finally, we outline our vision for COBRA modeling combined with meta-omics analyses and multivariate statistical analyses to inform and guide clinical trials, yield testable hypotheses, and ultimately propose novel dietary and therapeutic interventions.}, }
@article {pmid34313463, year = {2021}, author = {Lichtenstein, M and Turjerman, S and Pinto, JM and Barash, O and Koren, O}, title = {Pathophysiology of SARS-CoV-2 Infection in the Upper Respiratory Tract and Its Relation to Breath Volatile Organic Compounds.}, journal = {mSystems}, volume = {6}, number = {4}, pages = {e0010421}, pmid = {34313463}, issn = {2379-5077}, abstract = {Among the many products of metabolic processes are volatile organic compounds (VOCs). In the airways, these volatile metabolites are emitted through breathing and thus are easily sampled for analysis. Recent work has connected the functions and structure of the human microbiome with health and disease. Alteration in microbial function in this context can result in differences in metabolite composition, including that of VOCs, presenting the possibility of a new noninvasive method for clinical diagnosis. Screening methods that assess VOCs arising from changes in the airway microbiome could be highly useful in diagnosing viral upper respiratory tract infections (URTIs), e.g., COVID-19, which are highly contagious and have an enormous public health impact worldwide. A rapid noninvasive screening test for URTIs would pose major advantages in containing the disease. As early evidence shows that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection alters the human microbiome (both in the gut and the respiratory tract), we propose that detection of a VOC signature of an altered nasal microbiome could be fruitful as a rapid noninvasive measure of URTI in general and of SARS-CoV-2 in particular.}, }
@article {pmid34306841, year = {2021}, author = {Sumibcay, TJ and Lee-Jayaram, JJ and Yamamoto, LG}, title = {Reducing Broad-Spectrum Antibiotic Treatment of Simple Group A Streptococcal Infections to Reduce Harm to the Microbiome.}, journal = {Cureus}, volume = {13}, number = {6}, pages = {e15629}, pmid = {34306841}, issn = {2168-8184}, abstract = {Background Broad-spectrum antibiotics disrupt the human microbiome resulting in a greater risk of harmful, long-term conditions that impact human health. Group A streptococcal (GAS) infections can be treated with penicillin. Objective We examined the treatment of simple GAS infections to assess the use of broad-spectrum antibiotics. Methods Smart relational database extraction queries from January 1, 2016 to July 10, 2019 (3.6 years) of patients less than 22 years old in a 4-hospital system electronic medical record (EMR). Results We found 1778 non-ED outpatients and 873 ED patients with simple GAS infections who were not allergic to penicillin. A total of 75% and 44% of non-ED and ED patients were treated with broad-spectrum antibiotics, respectively (p < 0.001). Older patients were treated with penicillin alone more frequently than younger age groups (p < 0.001). Conclusion These findings highlight opportunities for clinicians to reduce the utilization of broad-spectrum antibiotics for the treatment of simple GAS infections to reduce harm to the microbiome.}, }
@article {pmid34302622, year = {2021}, author = {Hyun, DW and Lee, JY and Kim, MS and Shin, NR and Whon, TW and Kim, KH and Kim, PS and Tak, EJ and Jung, MJ and Lee, JY and Kim, HS and Kang, W and Sung, H and Jeon, CO and Bae, JW}, title = {Pathogenomics of Streptococcus ilei sp. nov., a newly identified pathogen ubiquitous in human microbiome.}, journal = {Journal of microbiology (Seoul, Korea)}, volume = {59}, number = {8}, pages = {792-806}, pmid = {34302622}, issn = {1976-3794}, mesh = {Adult ; Animals ; Gastrointestinal Microbiome ; Humans ; Ileostomy ; Male ; Mice ; Mice, Inbred C57BL ; *Microbiota ; Phylogeny ; Streptococcal Infections/*microbiology ; Streptococcus/classification/genetics/*isolation &amp; purification/*pathogenicity ; Virulence ; }, abstract = {Viridans group streptococci are a serious health concern because most of these bacteria cause life-threatening infections, especially in immunocompromised and hospitalized individuals. We focused on two alpha-hemolytic Streptococcus strains (I-G2 and I-P16) newly isolated from an ileostomy effluent of a colorectal cancer patient. We examined their pathogenic potential by investigating their prevalence in human and assessing their pathogenicity in a mouse model. We also predicted their virulence factors and pathogenic features by using comparative genomic analysis and in vitro tests. Using polyphasic and systematic approaches, we identified the isolates as belonging to a novel Streptococcus species and designated it as Streptococcus ilei. Metagenomic survey based on taxonomic assignment of datasets from the Human Microbiome Project revealed that S. ilei is present in most human population and at various body sites but is especially abundant in the oral cavity. Intraperitoneal injection of S. ilei was lethal to otherwise healthy C57BL/6J mice. Pathogenomics and in vitro assays revealed that S. ilei possesses a unique set of virulence factors. In agreement with the in vivo and in vitro data, which indicated that S. ilei strain I-G2 is more pathogenic than strain I-P16, only the former displayed the streptococcal group A antigen. We here newly identified S. ilei sp. nov., and described its prevalence in human, virulence factors, and pathogenicity. This will help to prevent S. ilei strain misidentification in the future, and improve the understanding and management of streptococcal infections.}, }
@article {pmid34296826, year = {2021}, author = {Gawlik, A and Salonen, A and Jian, C and Yanover, C and Antosz, A and Shmoish, M and Wasniewska, M and Bereket, A and Wudy, SA and Hartmann, MF and Thivel, D and Matusik, P and Weghuber, D and Hochberg, Z}, title = {Personalized approach to childhood obesity: Lessons from gut microbiota and omics studies. Narrative review and insights from the 29th European childhood obesity congress.}, journal = {Pediatric obesity}, volume = {16}, number = {10}, pages = {e12835}, doi = {10.1111/ijpo.12835}, pmid = {34296826}, issn = {2047-6310}, mesh = {Child ; Data Collection ; *Gastrointestinal Microbiome ; Humans ; Metabolomics ; *Pediatric Obesity/prevention &amp; control ; }, abstract = {The traditional approach to childhood obesity prevention and treatment should fit most patients, but misdiagnosis and treatment failure could be observed in some cases that lie away from average as part of individual variation or misclassification. Here, we reflect on the contributions that high-throughput technologies such as next-generation sequencing, mass spectrometry-based metabolomics and microbiome analysis make towards a personalized medicine approach to childhood obesity. We hypothesize that diagnosing a child as someone with obesity captures only part of the phenotype; and that metabolomics, genomics, transcriptomics and analyses of the gut microbiome, could add precision to the term "obese," providing novel corresponding biomarkers. Identifying a cluster -omic signature in a given child can thus facilitate the development of personalized prognostic, diagnostic, and therapeutic approaches. It can also be applied to the monitoring of symptoms/signs evolution, treatment choices and efficacy, predisposition to drug-related side effects and potential relapse. This article is a narrative review of the literature and summary of the main observations, conclusions and perspectives raised during the annual meeting of the European Childhood Obesity Group. Authors discuss some recent advances and future perspectives on utilizing a systems approach to understanding and managing childhood obesity in the context of the existing omics data.}, }
@article {pmid34294041, year = {2021}, author = {Andrade, BGN and Goris, T and Afli, H and Coutinho, FH and Dávila, AMR and Cuadrat, RRC}, title = {Putative mobilized colistin resistance genes in the human gut microbiome.}, journal = {BMC microbiology}, volume = {21}, number = {1}, pages = {220}, pmid = {34294041}, issn = {1471-2180}, mesh = {Colistin/*pharmacology ; Computational Biology ; Drug Resistance, Bacterial/*genetics ; Gene Transfer, Horizontal ; Genes, Bacterial/*genetics ; Genetic Variation ; Humans ; Microbiota/*drug effects/*genetics ; }, abstract = {BACKGROUND: The high incidence of bacterial genes that confer resistance to last-resort antibiotics, such as colistin, caused by mobilized colistin resistance (mcr) genes, poses an unprecedented threat to human health. Understanding the spread, evolution, and distribution of such genes among human populations will help in the development of strategies to diminish their occurrence. To tackle this problem, we investigated the distribution and prevalence of potential mcr genes in the human gut microbiome using a set of bioinformatics tools to screen the Unified Human Gastrointestinal Genome (UHGG) collection for the presence, synteny and phylogeny of putative mcr genes, and co-located antibiotic resistance genes.<br><br>RESULTS: A total of 2079 antibiotic resistance genes (ARGs) were classified as mcr genes in 2046 metagenome assembled genomes (MAGs), distributed across 1596 individuals from 41 countries, of which 215 were identified in plasmidial contigs. The genera that presented the largest number of mcr-like genes were Suterella and Parasuterella. Other potential pathogens carrying mcr genes belonged to the genus Vibrio, Escherichia and Campylobacter. Finally, we identified a total of 22,746 ARGs belonging to 21 different classes in the same 2046 MAGs, suggesting multi-resistance potential in the corresponding bacterial strains, increasing the concern of ARGs impact in the clinical settings.<br><br>CONCLUSION: This study uncovers the diversity of mcr-like genes in the human gut microbiome. We demonstrated the cosmopolitan distribution of these genes in individuals worldwide and the co-presence of other antibiotic resistance genes, including Extended-spectrum Beta-Lactamases (ESBL). Also, we described mcr-like genes fused to a PAP2-like domain in S. wadsworthensis. These novel sequences increase our knowledge about the diversity and evolution of mcr-like genes. Future research should focus on activity, genetic mobility and a potential colistin resistance in the corresponding strains to experimentally validate those findings.}, }
@article {pmid34289377, year = {2021}, author = {Zhang, XS and Yin, YS and Wang, J and Battaglia, T and Krautkramer, K and Li, WV and Li, J and Brown, M and Zhang, M and Badri, MH and Armstrong, AJS and Strauch, CM and Wang, Z and Nemet, I and Altomare, N and Devlin, JC and He, L and Morton, JT and Chalk, JA and Needles, K and Liao, V and Mount, J and Li, H and Ruggles, KV and Bonneau, RA and Dominguez-Bello, MG and Bäckhed, F and Hazen, SL and Blaser, MJ}, title = {Maternal cecal microbiota transfer rescues early-life antibiotic-induced enhancement of type 1 diabetes in mice.}, journal = {Cell host &amp; microbe}, volume = {29}, number = {8}, pages = {1249-1265.e9}, pmid = {34289377}, issn = {1934-6069}, support = {R01 DK120679/DK/NIDDK NIH HHS/United States ; R01 DK110014/DK/NIDDK NIH HHS/United States ; P01 HL147823/HL/NHLBI NIH HHS/United States ; R35 GM139655/GM/NIGMS NIH HHS/United States ; R01 GM128955/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Anti-Bacterial Agents/*pharmacology ; Autoimmune Diseases ; Bacteria/classification/drug effects ; Cecum/*immunology/*microbiology ; Diabetes Mellitus, Type 1/*immunology ; Disease Models, Animal ; Female ; Gastrointestinal Microbiome/*drug effects/*physiology ; Gene Expression ; Histone Code ; Intestines/immunology ; Male ; Metabolic Networks and Pathways ; Metagenome ; Mice ; Mice, Inbred NOD ; MicroRNAs ; }, abstract = {Early-life antibiotic exposure perturbs the intestinal microbiota and accelerates type 1 diabetes (T1D) development in the NOD mouse model. Here, we found that maternal cecal microbiota transfer (CMT) to NOD mice after early-life antibiotic perturbation largely rescued the induced T1D enhancement. Restoration of the intestinal microbiome was significant and persistent, remediating the antibiotic-depleted diversity, relative abundance of particular taxa, and metabolic pathways. CMT also protected against perturbed metabolites and normalized innate and adaptive immune effectors. CMT restored major patterns of ileal microRNA and histone regulation of gene expression. Further experiments suggest a gut-microbiota-regulated T1D protection mechanism centered on Reg3γ, in an innate intestinal immune network involving CD44, TLR2, and Reg3γ. This regulation affects downstream immunological tone, which may lead to protection against tissue-specific T1D injury.}, }
@article {pmid34282932, year = {2021}, author = {Brubaker, L and Gourdine, JF and Siddiqui, NY and Holland, A and Halverson, T and Limeria, R and Pride, D and Ackerman, L and Forster, CS and Jacobs, KM and Thomas-White, KJ and Putonti, C and Dong, Q and Weinstein, M and Lukacz, ES and Karstens, L and Wolfe, AJ}, title = {Forming Consensus To Advance Urobiome Research.}, journal = {mSystems}, volume = {6}, number = {4}, pages = {e0137120}, pmid = {34282932}, issn = {2379-5077}, support = {K01 DK116706/DK/NIDDK NIH HHS/United States ; R13 DK120286/DK/NIDDK NIH HHS/United States ; }, abstract = {Urobiome research has the potential to advance the understanding of a wide range of diseases, including lower urinary tract symptoms and kidney disease. Many scientific areas have benefited from early research method consensus to facilitate the greater, common good. This consensus document, developed by a group of expert investigators currently engaged in urobiome research (UROBIOME 2020 conference participants), aims to promote standardization and advances in this field by the adoption of common core research practices. We propose a standardized nomenclature as well as considerations for specimen collection, preservation, storage, and processing. Best practices for urobiome study design include our proposal for standard metadata elements as part of core metadata collection. Although it is impractical to follow fixed analytical procedures when analyzing urobiome data, we propose guidelines to document and report data originating from urobiome studies. We offer this first consensus document with every expectation of subsequent revision as our field progresses.}, }
@article {pmid34282723, year = {2021}, author = {Diebold, PJ and New, FN and Hovan, M and Satlin, MJ and Brito, IL}, title = {Linking plasmid-based beta-lactamases to their bacterial hosts using single-cell fusion PCR.}, journal = {eLife}, volume = {10}, number = {}, pages = {}, pmid = {34282723}, issn = {2050-084X}, support = {DP2 HL141007/HL/NHLBI NIH HHS/United States ; K23 AI114994/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Anti-Bacterial Agents/pharmacology ; Bacterial Proteins/genetics ; Cell Fusion/*methods ; Chickens/microbiology ; Clostridiales/genetics ; Drug Resistance, Multiple, Bacterial/genetics ; Feces/microbiology ; Gene Transfer, Horizontal ; Humans ; Klebsiella pneumoniae/genetics ; Microbiota/genetics ; Plasmids/*genetics ; Polymerase Chain Reaction/*methods ; RNA, Ribosomal, 16S ; beta-Lactamases/*genetics/metabolism ; }, abstract = {The horizonal transfer of plasmid-encoded genes allows bacteria to adapt to constantly shifting environmental pressures, bestowing functional advantages to their bacterial hosts such as antibiotic resistance, metal resistance, virulence factors, and polysaccharide utilization. However, common molecular methods such as short- and long-read sequencing of microbiomes cannot associate extrachromosomal plasmids with the genome of the host bacterium. Alternative methods to link plasmids to host bacteria are either laborious, expensive, or prone to contamination. Here we present the One-step Isolation and Lysis PCR (OIL-PCR) method, which molecularly links plasmid-encoded genes with the bacterial 16S rRNA gene via fusion PCR performed within an emulsion. After validating this method, we apply it to identify the bacterial hosts of three clinically relevant beta-lactamases within the gut microbiomes of neutropenic patients, as they are particularly vulnerable multidrug-resistant infections. We successfully detect the known association of a multi-drug resistant plasmid with Klebsiella pneumoniae, as well as the novel associations of two low-abundance genera, Romboutsia and Agathobacter. Further investigation with OIL-PCR confirmed that our detection of Romboutsia is due to its physical association with Klebsiella as opposed to directly harboring the beta-lactamase genes. Here we put forth a robust, accessible, and high-throughput platform for sensitively surveying the bacterial hosts of mobile genes, as well as detecting physical bacterial associations such as those occurring within biofilms and complex microbial communities.}, }
@article {pmid34281323, year = {2021}, author = {Gargiulo Isacco, C and Inchingolo, AD and Nguyen Cao, KD and Malcangi, G and Paduanelli, G and Pham Hung, V and Tran Cong, T and Bordea, IR and Scarano, A and Laforgia, A and Marinelli, G and Limongelli, L and Inchingolo, F and Lorusso, F and Inchingolo, AM and Dipalma, G}, title = {The bad relationship, osteo-decay and diabetes type 2 searching for a link: a literature review.}, journal = {Journal of biological regulators and homeostatic agents}, volume = {35}, number = {2 Suppl. 1}, pages = {253-269}, doi = {10.23812/21-2supp1-26}, pmid = {34281323}, issn = {0393-974X}, mesh = {Bone and Bones ; *Diabetes Mellitus, Type 2 ; *Gastrointestinal Microbiome ; Hematopoiesis ; Humans ; *Metabolic Diseases ; }, abstract = {The diabetes and osteoporotic metabolic diseases are characterized by a wide prevalence of the population worldwide and correlated to alteration of the bone tissues. Several cofactors could influence the clinical course and the biochemistry of the pathologies such as human microbiome, nutrition characteristics, gut microbiota activity and interactions with vitamin K and D across IGF/GH and TP53 signaling pathways and the glucose/energy as mechanism for bone tissue health. Moreover, also the calories and sugar consumption seem to be correlated to an increased inflammatory state with several consequences for hematopoiesis and host tissues response. The aim of the present literature review was to highlight the role of osteoporotic diseases and diabetes type 2 link for the bone metabolism. The literature cases showed that a correlation between bone-gut-kidney-heart-CNS-Immunity crosstalk seems to be linked with bone metabolism and health regulation. Moreover, also the aging process could represent a valuable co-factor for the sustaining of the metabolic disorders upon a multi-systemic level.}, }
@article {pmid34272085, year = {2021}, author = {Hammond, AM and Monir, RL and Schoch, JJ}, title = {The role of the pediatric cutaneous and gut microbiomes in childhood disease: A review.}, journal = {Seminars in perinatology}, volume = {45}, number = {6}, pages = {151452}, doi = {10.1016/j.semperi.2021.151452}, pmid = {34272085}, issn = {1558-075X}, mesh = {Child ; Child, Preschool ; *Dermatitis, Atopic ; *Gastrointestinal Microbiome ; Humans ; *Microbiota ; Skin ; }, abstract = {OBJECTIVE: Infancy and early childhood are crucial periods in the development of the human microbiome and shape the trajectory of microbial colonization, immune system development, and systemic disease. We review the development of the skin and gut microbiomes, their connection to the immune system, and their relevance to common pediatric pathologies.<br><br>FINDINGS: Beginning after birth, and likely even in utero, colonization of the skin and the gut occur in parallel, influenced by external factors. This colonization, in turn, dictates maturation of the immune system and contributes to conditions from atopic dermatitis to sepsis. Emerging literature is identifying links between the gut and skin microbiomes.<br><br>CONCLUSION: The gut and skin microbiomes are associated with pediatric disease states. Immune and microbial plasticity make this unique period an ideal target for intervention. Investigating the purposeful manipulation of the pediatric microbiome may lead to novel treatment and prevention strategies.}, }
@article {pmid34269346, year = {2021}, author = {Bai, J and Zhang, W and Amirkhanzadeh Barandouzir, Z}, title = {Human Microbiome: Understanding the Role of the Gut Microbiome and Implications for Oncology Nursing Care.}, journal = {Clinical journal of oncology nursing}, volume = {25}, number = {4}, pages = {383-387}, pmid = {34269346}, issn = {1538-067X}, support = {K99 NR017897/NR/NINR NIH HHS/United States ; R00 NR017897/NR/NINR NIH HHS/United States ; R25 CA203650/CA/NCI NIH HHS/United States ; }, mesh = {Dysbiosis ; *Gastrointestinal Microbiome ; Humans ; *Microbiota ; *Neoplasms ; Oncology Nursing ; }, abstract = {By understanding the human microbiome and its influencing factors, oncology nurses in clinical practice can educate, screen, and monitor patients with cancer who have a higher risk of gut microbiome dysbiosis. Knowledge of the gut microbiome and its impact on cancer outcomes can help oncology nurses interpret associations between the gut microbiome and treatment- related toxicities and symptoms. Oncology nurses can guide patients to build a healthy gut microbiome across the trajectory of cancer treatment and survivorship.}, }
@article {pmid34267333, year = {2022}, author = {Javier-DesLoges, J and McKay, RR and Swafford, AD and Sepich-Poore, GD and Knight, R and Parsons, JK}, title = {The microbiome and prostate cancer.}, journal = {Prostate cancer and prostatic diseases}, volume = {25}, number = {2}, pages = {159-164}, pmid = {34267333}, issn = {1476-5608}, support = {F30 CA243480/CA/NCI NIH HHS/United States ; R01 CA241728/CA/NCI NIH HHS/United States ; U24 CA248454/CA/NCI NIH HHS/United States ; }, mesh = {Feces ; Humans ; Male ; *Microbiota ; Prostate ; *Prostatic Neoplasms/diagnosis/therapy ; }, abstract = {There is growing evidence that the microbiome is involved in development and treatment of many human diseases, including prostate cancer. There are several potential pathways for microbiome-based mechanisms for the development of prostate cancer: direct impacts of microbes or microbial products in the prostate or the urine, and indirect impacts from microbes or microbial products in the gastrointestinal tract. Unique microbial signatures have been identified within the stool, oral cavity, tissue, urine, and blood of prostate cancer patients, but studies vary in their findings. Recent studies describe potential diagnostic and therapeutic applications of the microbiome, but further clinical investigation is needed. In this review, we explore the existing literature on the discovery of the human microbiome and its relationship to prostate cancer.}, }
@article {pmid34262212, year = {2021}, author = {Han, S and Van Treuren, W and Fischer, CR and Merrill, BD and DeFelice, BC and Sanchez, JM and Higginbottom, SK and Guthrie, L and Fall, LA and Dodd, D and Fischbach, MA and Sonnenburg, JL}, title = {A metabolomics pipeline for the mechanistic interrogation of the gut microbiome.}, journal = {Nature}, volume = {595}, number = {7867}, pages = {415-420}, pmid = {34262212}, issn = {1476-4687}, support = {R01 DK101674/DK/NIDDK NIH HHS/United States ; DP1 AT009892/AT/NCCIH NIH HHS/United States ; K08 DK110335/DK/NIDDK NIH HHS/United States ; P01 HL147823/HL/NHLBI NIH HHS/United States ; R01 DK085025/DK/NIDDK NIH HHS/United States ; F32 AG062119/AG/NIA NIH HHS/United States ; DP1 DK113598/DK/NIDDK NIH HHS/United States ; T32 AI007328/AI/NIAID NIH HHS/United States ; 5T32 AI007328-32/NH/NIH HHS/United States ; }, mesh = {Animals ; Bacteria/classification/genetics/*metabolism ; Bacteroides/genetics/metabolism ; *Gastrointestinal Microbiome ; Genes, Bacterial/genetics ; Genomics ; Host Microbial Interactions ; Humans ; Male ; *Metabolome ; Metabolomics/*methods ; Mice ; Nitrogen/metabolism ; Phenotype ; Phylogeny ; }, abstract = {Gut microorganisms modulate host phenotypes and are associated with numerous health effects in humans, ranging from host responses to cancer immunotherapy to metabolic disease and obesity. However, difficulty in accurate and high-throughput functional analysis of human gut microorganisms has hindered efforts to define mechanistic connections between individual microbial strains and host phenotypes. One key way in which the gut microbiome influences host physiology is through the production of small molecules[1-3], yet progress in elucidating this chemical interplay has been hindered by limited tools calibrated to detect the products of anaerobic biochemistry in the gut. Here we construct a microbiome-focused, integrated mass-spectrometry pipeline to accelerate the identification of microbiota-dependent metabolites in diverse sample types. We report the metabolic profiles of 178 gut microorganism strains using our library of 833 metabolites. Using this metabolomics resource, we establish deviations in the relationships between phylogeny and metabolism, use machine learning to discover a previously undescribed type of metabolism in Bacteroides, and reveal candidate biochemical pathways using comparative genomics. Microbiota-dependent metabolites can be detected in diverse biological fluids from gnotobiotic and conventionally colonized mice and traced back to the corresponding metabolomic profiles of cultured bacteria. Collectively, our microbiome-focused metabolomics pipeline and interactive metabolomics profile explorer are a powerful tool for characterizing microorganisms and interactions between microorganisms and their host.}, }
@article {pmid34261503, year = {2021}, author = {Karcher, N and Nigro, E and Punčochář, M and Blanco-Míguez, A and Ciciani, M and Manghi, P and Zolfo, M and Cumbo, F and Manara, S and Golzato, D and Cereseto, A and Arumugam, M and Bui, TPN and Tytgat, HLP and Valles-Colomer, M and de Vos, WM and Segata, N}, title = {Genomic diversity and ecology of human-associated Akkermansia species in the gut microbiome revealed by extensive metagenomic assembly.}, journal = {Genome biology}, volume = {22}, number = {1}, pages = {209}, pmid = {34261503}, issn = {1474-760X}, support = {U01 CA230551/CA/NCI NIH HHS/United States ; }, mesh = {Akkermansia/classification/genetics/metabolism/virology ; Animals ; Bacteriophages/growth &amp; development ; Clustered Regularly Interspaced Short Palindromic Repeats ; Gastrointestinal Microbiome/*genetics ; Genetic Variation ; *Genome, Bacterial ; Humans ; *Metagenome ; Mice ; Operon ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; }, abstract = {BACKGROUND: Akkermansia muciniphila is a human gut microbe with a key role in the physiology of the intestinal mucus layer and reported associations with decreased body mass and increased gut barrier function and health. Despite its biomedical relevance, the genomic diversity of A. muciniphila remains understudied and that of closely related species, except for A. glycaniphila, unexplored.<br><br>RESULTS: We present a large-scale population genomics analysis of the Akkermansia genus using 188 isolate genomes and 2226 genomes assembled from 18,600 metagenomes from humans and other animals. While we do not detect A. glycaniphila, the Akkermansia strains in the human gut can be grouped into five distinct candidate species, including A. muciniphila, that show remarkable whole-genome divergence despite surprisingly similar 16S rRNA gene sequences. These candidate species are likely human-specific, as they are detected in mice and non-human primates almost exclusively when kept in captivity. In humans, Akkermansia candidate species display ecological co-exclusion, diversified functional capabilities, and distinct patterns of associations with host body mass. Analysis of CRISPR-Cas loci reveals new variants and spacers targeting newly discovered putative bacteriophages. Remarkably, we observe an increased relative abundance of Akkermansia when cognate predicted bacteriophages are present, suggesting ecological interactions. A. muciniphila further exhibits subspecies-level genetic stratification with associated functional differences such as a putative exo/lipopolysaccharide operon.<br><br>CONCLUSIONS: We uncover a large phylogenetic and functional diversity of the Akkermansia genus in humans. This variability should be considered in the ongoing experimental and metagenomic efforts to characterize the health-associated properties of A. muciniphila and related bacteria.}, }
@article {pmid34260950, year = {2022}, author = {McCoubrey, LE and Gaisford, S and Orlu, M and Basit, AW}, title = {Predicting drug-microbiome interactions with machine learning.}, journal = {Biotechnology advances}, volume = {54}, number = {}, pages = {107797}, doi = {10.1016/j.biotechadv.2021.107797}, pmid = {34260950}, issn = {1873-1899}, mesh = {*Gastrointestinal Microbiome/physiology ; Humans ; Machine Learning ; *Microbiota ; }, abstract = {Pivotal work in recent years has cast light on the importance of the human microbiome in maintenance of health and physiological response to drugs. It is now clear that gastrointestinal microbiota have the metabolic power to promote, inactivate, or even toxify the efficacy of a drug to a level of clinically relevant significance. At the same time, it appears that drug intake has the propensity to alter gut microbiome composition, potentially affecting health and response to other drugs. Since the precise composition of an individual's microbiome is unique, one's drug-microbiome relationship is similarly unique. Thus, in the age of evermore personalised medicine, the ability to predict individuals' drug-microbiome interactions is highly sought. Machine learning (ML) offers a powerful toolkit capable of characterising and predicting drug-microbiota interactions at the individual patient level. ML techniques have the potential to learn the mechanisms operating drug-microbiome activities and measure patients' risk of such occurrences. This review will outline current knowledge at the drug-microbiota interface, and present ML as a technique for examining and forecasting personalised drug-microbiome interactions. When harnessed effectively, ML could alter how the pharmaceutical industry and healthcare professionals consider the drug-microbiome axis in patient care.}, }
@article {pmid34256346, year = {2021}, author = {Jian, C and Carpén, N and Helve, O and de Vos, WM and Korpela, K and Salonen, A}, title = {Early-life gut microbiota and its connection to metabolic health in children: Perspective on ecological drivers and need for quantitative approach.}, journal = {EBioMedicine}, volume = {69}, number = {}, pages = {103475}, pmid = {34256346}, issn = {2352-3964}, mesh = {Child ; Environment ; *Gastrointestinal Microbiome ; Humans ; Metabolic Diseases/epidemiology/*microbiology ; }, abstract = {The colonisation and development of the gut microbiota has been implicated in paediatric metabolic disorders via its powerful effect on host metabolic and immune homeostasis. Here we summarise the evidence from human studies on the early gut microbiota and paediatric overweight and obesity. Manipulation of the early gut microbiota may represent a promising target for countering the burgeoning metabolic disorders in the paediatric population, provided the assembly patterns of microbiota and their health consequences can be decoded. Therefore, in this review, we pay particular attention to the important ecological drivers affecting the community dynamics of the early gut microbiota. We then discuss the knowledge gaps in commonly studied exposures linking the gut microbiota to metabolic disorders, especially regarding maternal factors and antibiotic use. This review also attempts to give directions for future studies aiming to identify predictive and corrective measures for paediatric metabolic disorders based on the gut microbiota. Gut microbiota; Metabolism; Paediatric overweight and obesity; Ecological driver; Dynamics; Infants.}, }
@article {pmid34256014, year = {2021}, author = {Wastyk, HC and Fragiadakis, GK and Perelman, D and Dahan, D and Merrill, BD and Yu, FB and Topf, M and Gonzalez, CG and Van Treuren, W and Han, S and Robinson, JL and Elias, JE and Sonnenburg, ED and Gardner, CD and Sonnenburg, JL}, title = {Gut-microbiota-targeted diets modulate human immune status.}, journal = {Cell}, volume = {184}, number = {16}, pages = {4137-4153.e14}, pmid = {34256014}, issn = {1097-4172}, support = {F32 AG062119/AG/NIA NIH HHS/United States ; R01 DK085025/DK/NIDDK NIH HHS/United States ; T32 AI007328/AI/NIAID NIH HHS/United States ; }, mesh = {Biodiversity ; *Diet ; Dietary Fiber/pharmacology ; Feeding Behavior ; Female ; Fermented Foods ; *Gastrointestinal Microbiome/drug effects ; Humans ; *Immunity ; Inflammation/pathology ; Male ; Middle Aged ; Signal Transduction/drug effects ; }, abstract = {Diet modulates the gut microbiome, which in turn can impact the immune system. Here, we determined how two microbiota-targeted dietary interventions, plant-based fiber and fermented foods, influence the human microbiome and immune system in healthy adults. Using a 17-week randomized, prospective study (n = 18/arm) combined with -omics measurements of microbiome and host, including extensive immune profiling, we found diet-specific effects. The high-fiber diet increased microbiome-encoded glycan-degrading carbohydrate active enzymes (CAZymes) despite stable microbial community diversity. Although cytokine response score (primary outcome) was unchanged, three distinct immunological trajectories in high-fiber consumers corresponded to baseline microbiota diversity. Alternatively, the high-fermented-food diet steadily increased microbiota diversity and decreased inflammatory markers. The data highlight how coupling dietary interventions to deep and longitudinal immune and microbiome profiling can provide individualized and population-wide insight. Fermented foods may be valuable in countering the decreased microbiome diversity and increased inflammation pervasive in industrialized society.}, }
@article {pmid34248864, year = {2021}, author = {Kostopoulos, I and Aalvink, S and Kovatcheva-Datchary, P and Nijsse, B and Bäckhed, F and Knol, J and de Vos, WM and Belzer, C}, title = {A Continuous Battle for Host-Derived Glycans Between a Mucus Specialist and a Glycan Generalist in vitro and in vivo.}, journal = {Frontiers in microbiology}, volume = {12}, number = {}, pages = {632454}, pmid = {34248864}, issn = {1664-302X}, abstract = {The human gastrointestinal tract is colonized by a diverse microbial community, which plays a crucial role in human health. In the gut, a protective mucus layer that consists of glycan structures separates the bacteria from the host epithelial cells. These host-derived glycans are utilized by bacteria that have adapted to this specific compound in the gastrointestinal tract. Our study investigated the close interaction between two distinct gut microbiota members known to use mucus glycans, the generalist Bacteroides thetaiotaomicron and the specialist Akkermansia muciniphila in vitro and in vivo. The in vitro study, in which mucin was the only nutrient source, indicated that B. thetaiotaomicron significantly upregulated genes coding for Glycoside Hydrolases (GHs) and mucin degradation activity when cultured in the presence of A. muciniphila. Furthermore, B. thetaiotaomicron significantly upregulated the expression of a gene encoding for membrane attack complex/perforin (MACPF) domain in co-culture. The transcriptome analysis also indicated that A. muciniphila was less affected by the environmental changes and was able to sustain its abundance in the presence of B. thetaiotaomicron while increasing the expression of LPS core biosynthesis activity encoding genes (O-antigen ligase, Lipid A and Glycosyl transferases) as well as ABC transporters. Using germ-free mice colonized with B. thetaiotaomicron and/or A. muciniphila, we observed a more general glycan degrading profile in B. thetaiotaomicron while the expression profile of A. muciniphila was not significantly affected when colonizing together, indicating that two different nutritional niches were established in mice gut. Thus, our results indicate that a mucin degrading generalist adapts to its changing environment, depending on available carbohydrates while a mucin degrading specialist adapts by coping with competing microorganism through upregulation of defense related genes.}, }
@article {pmid34244284, year = {2021}, author = {Koskenvuo, L and Lunkka, P and Varpe, P and Hyöty, M and Satokari, R and Haapamäki, C and Lepistö, A and Sallinen, V}, title = {Mechanical bowel preparation and oral antibiotics versus mechanical bowel preparation only prior rectal surgery (MOBILE2): a multicentre, double-blinded, randomised controlled trial-study protocol.}, journal = {BMJ open}, volume = {11}, number = {7}, pages = {e051269}, pmid = {34244284}, issn = {2044-6055}, mesh = {*Anti-Bacterial Agents/therapeutic use ; Colon/surgery ; Humans ; Multicenter Studies as Topic ; Preoperative Care ; Randomized Controlled Trials as Topic ; Rectum/surgery ; Retrospective Studies ; *Surgical Wound Infection/prevention &amp; control ; }, abstract = {INTRODUCTION: Mechanical bowel preparation (MBP) prior to rectal surgery is widely used. Based on retrospective data many guidelines recommend mechanical and oral antibiotic bowel preparation (MOABP) to reduce postoperative complications and specifically surgical site infections (SSIs). The primary aim of this study is to examine whether MOABP reduces complications of rectal surgery.<br><br>METHODS AND ANALYSIS: The MOBILE2 (Mechanical Bowel Preparation and Oral Antibiotics vs Mechanical Bowel Preparation Only Prior Rectal Surgery) trial is a multicentre, double-blinded, parallel group, superiority, randomised controlled trial comparing MOABP to MBP among patients scheduled for rectal surgery with colorectal or coloanal anastomosis. The patients randomised to the MOABP group receive 1&#x2009;g neomycin and 1&#x2009;g metronidazole two times on a day prior to surgery and patients randomised to the MBP group receive identical placebo. Based on power calculations, 604 patients will be enrolled in the study. The primary outcome is Comprehensive Complication Index within 30 days after surgery. Secondary outcomes are SSIs within 30 days after surgery, the number and classification of anastomosis dehiscences, the length of hospital stay, mortality within 90 days after surgery and the number of patients who received adjuvant treatment if needed. Tertiary outcomes are overall survival, disease-specific survival, recurrence-free survival and difference in quality-of-life before and 1&#x2009;year after surgery. In addition, the microbiota differences in colon mucosa are analysed.<br><br>ETHICS AND DISSEMINATION: The Ethics Committee of Helsinki University Hospital approved the study. The findings will be disseminated in peer-reviewed academic journals.<br><br>TRIAL REGISTRATION NUMBER: NCT04281667.}, }
@article {pmid34242413, year = {2021}, author = {Tuganbaev, T and Honda, K}, title = {Non-zero-sum microbiome immune system interactions.}, journal = {European journal of immunology}, volume = {51}, number = {9}, pages = {2120-2136}, pmid = {34242413}, issn = {1521-4141}, mesh = {Adaptive Immunity/immunology ; Enteric Nervous System/*physiology ; Gastrointestinal Microbiome/*immunology ; Gastrointestinal Tract/*immunology/innervation/*microbiology/physiology ; Humans ; Immunity, Innate/immunology ; Symbiosis/immunology ; }, abstract = {Fundamental asymmetries between the host and its microbiome in enzymatic activities and nutrient storage capabilities have promoted mutualistic adaptations on both sides. As a result, the enteric immune system has evolved so as not to cause a zero-sum sterilization of non-self, but rather achieve a non-zero-sum self-reinforcing cooperation with its evolutionary partner the microbiome. In this review, we attempt to integrate the accumulated knowledge of immune-microbiome interactions into an evolutionary framework and trace the pattern of positive immune-microbiome feedback loops across epithelial, enteric nervous system, innate, and adaptive immune circuits. Indeed, the immune system requires commensal signals for its development and function, and reciprocally protects the microbiome from nutrient shortage and pathogen outgrowth. In turn, a healthy microbiome is the result of immune system curatorship as well as microbial ecology. The paradigms of host-microbiome asymmetry and the cooperative nature of their interactions identified in the gut are applicable across all tissues influenced by microbial activities. Incorporation of immune system influences into models of microbiome ecology will be a step forward toward defining what constitutes a healthy human microbiome and guide discoveries of novel host-microbiome mutualistic adaptations that may be harnessed for the promotion of human health.}, }
@article {pmid34239510, year = {2021}, author = {Young, RB and Marcelino, VR and Chonwerawong, M and Gulliver, EL and Forster, SC}, title = {Key Technologies for Progressing Discovery of Microbiome-Based Medicines.}, journal = {Frontiers in microbiology}, volume = {12}, number = {}, pages = {685935}, pmid = {34239510}, issn = {1664-302X}, abstract = {A growing number of experimental and computational approaches are illuminating the "microbial dark matter" and uncovering the integral role of commensal microbes in human health. Through this work, it is now clear that the human microbiome presents great potential as a therapeutic target for a plethora of diseases, including inflammatory bowel disease, diabetes and obesity. The development of more efficacious and targeted treatments relies on identification of causal links between the microbiome and disease; with future progress dependent on effective links between state-of-the-art sequencing approaches, computational analyses and experimental assays. We argue determining causation is essential, which can be attained by generating hypotheses using multi-omic functional analyses and validating these hypotheses in complex, biologically relevant experimental models. In this review we discuss existing analysis and validation methods, and propose best-practice approaches required to enable the next phase of microbiome research.}, }
@article {pmid34237996, year = {2021}, author = {Paglia, L}, title = {From native core micriobiome to milk-oriented microbiome.}, journal = {European journal of paediatric dentistry}, volume = {22}, number = {2}, pages = {89}, doi = {10.23804/ejpd.2021.22.02.1}, pmid = {34237996}, issn = {2035-648X}, mesh = {Breast Feeding ; Child ; Female ; Humans ; Infant ; Infant, Newborn ; *Microbiota ; Milk, Human ; Mothers ; Pregnancy ; }, abstract = {The human microbiome is the full set of microorganisms (microbiota) present on and in our body. Its importance is such that the human being has been defined as a holobiont, that is, a superorganism made up of human eukaryotic cells and microbial cells. A balanced microbiota (eubiosis) is a prerequisite for health and well-being; on the contrary, an altered microbiota (dysbiosis) is the cause of pathological conditions. This concept is the cornerstone of the "microbiota revolution": Currently there is no disease that cannot be re- interpreted as a function of microbiome. While all human beings have similar DNA, it is the microbiome that make every person genetically unique; therefore the microbiome is the variable component of the genome which characterises each one of us. About one third of the microbiome is common to all individuals, while two thirds are specific to each subject and constitute a sort of fingerprint that forms and stabilises in the first 2-3 years of life. This timeframe is extremely important since it has been shown that the structure of the microbiome is already acquired in the embryonic-fetal period, it is completed within 3 years and lasts a lifetime. The native core microbiome is the first microbiota and characterises individuals for their whole life. It is affected by four main variables: The quality of family and social life of the mother-to-be, the intake of drugs during pregnancy, as well as the type of birth and breastfeeding. It is renowned that breast milk is a complex, unique and essential food for the growth of the child, but one of its functions - which is still under investigation today - is to feed and guide the formation of the microbiome of the newborn even after the introduction of solid foods, during the first 3 years of life. This function is carried out by the over one hundred different types of oligosaccharides that are present in breast milk, which is why these days we talk about the so-called MOM (milk-oriented microbiome). The correct formation of the microbiome affects the entire life of an individual. This is a more than valid reason to promote breastfeeding even after eruption of baby teeth and throughout the weaning period. The role of pediatric dentists, together with hygienists and pediatricians, is to spread and stress out the importance of oral hygiene so that breastfeeding can only bring benefits and not carious lesions!}, }
@article {pmid34234185, year = {2021}, author = {Jones, J and Reinke, SN and Ali, A and Palmer, DJ and Christophersen, CT}, title = {Fecal sample collection methods and time of day impact microbiome composition and short chain fatty acid concentrations.}, journal = {Scientific reports}, volume = {11}, number = {1}, pages = {13964}, pmid = {34234185}, issn = {2045-2322}, mesh = {Biodiversity ; Cluster Analysis ; Fatty Acids, Volatile/analysis/*metabolism ; Feces/*microbiology ; *Gastrointestinal Microbiome ; Humans ; Metagenome ; Metagenomics/methods ; Microbial Viability ; Specimen Handling/*methods ; }, abstract = {Associations between the human gut microbiome and health outcomes continues to be of great interest, although fecal sample collection methods which impact microbiome studies are sometimes neglected. Here, we expand on previous work in sample optimization, to promote high quality microbiome data. To compare fecal sample collection methods, amplicons from the bacterial 16S rRNA gene (V4) and fungal (ITS2) region, as well as short chain fatty acid (SCFA) concentrations were determined in fecal material over three timepoints. We demonstrated that spot sampling of stool results in variable detection of some microbial members, and inconsistent levels of SCFA; therefore, sample homogenization prior to subsequent analysis or subsampling is recommended. We also identify a trend in microbial and metabolite composition that shifts over two consecutive stool collections less than 25 h apart. Lastly, we show significant differences in bacterial composition that result from collecting stool samples in OMNIgene·Gut tube (DNA Genotec) or Stool Nucleic Acid Collection and Preservation Tube (NORGEN) compared to immediate freezing. To assist with planning fecal sample collection and storage procedures for microbiome investigations with multiple analyses, we recommend participants to collect the first full bowel movement of the day and freeze the sample immediately after collection.}, }
@article {pmid34233595, year = {2021}, author = {Liao, B and Ye, X and Chen, X and Zhou, Y and Cheng, L and Zhou, X and Ren, B}, title = {The two-component signal transduction system and its regulation in Candida albicans.}, journal = {Virulence}, volume = {12}, number = {1}, pages = {1884-1899}, pmid = {34233595}, issn = {2150-5608}, mesh = {Antifungal Agents/pharmacology ; *Candida albicans/genetics/metabolism ; *Fungal Proteins/genetics/metabolism ; Humans ; *Signal Transduction ; Virulence ; }, abstract = {Candida albicans, which can cause superficial and life-threatening systemic infections, is the most common opportunistic fungal pathogen in the human microbiome. The two-component system is one of the most important C. albicans signal transduction pathways, regulating the response to oxidative and osmotic stresses, adhesion, morphogenesis, cell wall synthesis, virulence, drug resistance, and the host-pathogen interactions. Notably, some components of this signaling pathway have not been found in the human genome, indicating that the two-component system of C. albicans can be a potential target for new antifungal agents. Here, we summarize the composition, signal transduction, and regulation of the two-component system of C. albicans to emphasize its essential roles in the pathogenesis of C. albicans and the new therapeutic target for antifungal drugs.}, }
@article {pmid34228753, year = {2021}, author = {Cabrera, LE and Pekkarinen, PT and Alander, M and Nowlan, KHA and Nguyen, NA and Jokiranta, S and Kuivanen, S and Patjas, A and Mero, S and Pakkanen, SH and Heinonen, S and Kantele, A and Vapalahti, O and Kekäläinen, E and Strandin, T}, title = {Characterization of low-density granulocytes in COVID-19.}, journal = {PLoS pathogens}, volume = {17}, number = {7}, pages = {e1009721}, pmid = {34228753}, issn = {1553-7374}, mesh = {Acute Disease ; Adult ; Aged ; COVID-19/blood/*immunology ; Case-Control Studies ; Cohort Studies ; Convalescence ; Disease Progression ; Female ; Follow-Up Studies ; Granulocytes/*classification/cytology ; Humans ; Immune Tolerance/immunology ; Male ; Middle Aged ; Scavenger Receptors, Class E/analysis ; Severity of Illness Index ; }, abstract = {Severe COVID-19 is characterized by extensive pulmonary complications, to which host immune responses are believed to play a role. As the major arm of innate immunity, neutrophils are one of the first cells recruited to the site of infection where their excessive activation can contribute to lung pathology. Low-density granulocytes (LDGs) are circulating neutrophils, whose numbers increase in some autoimmune diseases and cancer, but are poorly characterized in acute viral infections. Using flow cytometry, we detected a significant increase of LDGs in the blood of acute COVID-19 patients, compared to healthy controls. Based on their surface marker expression, COVID-19-related LDGs exhibit four different populations, which display distinctive stages of granulocytic development and most likely reflect emergency myelopoiesis. Moreover, COVID-19 LDGs show a link with an elevated recruitment and activation of neutrophils. Functional assays demonstrated the immunosuppressive capacities of these cells, which might contribute to impaired lymphocyte responses during acute disease. Taken together, our data confirms a significant granulocyte activation during COVID-19 and suggests that granulocytes of lower density play a role in disease progression.}, }
@article {pmid34228203, year = {2022}, author = {Schwierzeck, V and Hülpüsch, C and Reiger, M}, title = {Microbiome of Barrier Organs in Allergy: Who Runs the World? Germs!.}, journal = {Handbook of experimental pharmacology}, volume = {268}, number = {}, pages = {53-65}, pmid = {34228203}, issn = {0171-2004}, mesh = {*Dermatitis, Atopic ; Dysbiosis ; *Food Hypersensitivity ; Humans ; *Microbiota ; *Rhinitis, Allergic ; }, abstract = {Over the last few decades, allergic diseases have been steadily increasing worldwide, a phenomenon that is not yet completely understood. Recent evidence, however, suggests that alterations in the microbiome may be a contributing factor. The microbiome refers to all microorganisms in a habitat including bacteria, fungi, and viruses. Using modern sequencing technologies, we are now capable of detecting and analyzing the human microbiome in more detail than ever before. Epidemiological and experimental studies have indicated that a complex intestinal microbiome supports the development of the immune system during childhood, thus providing protection from allergic diseases, including food allergy. The microbiome becomes an important part of human physiology and forms dynamic relationships with our various barrier systems. For example, bacterial dysbiosis is a hallmark of atopic eczema and correlates with disease progression. Similarly, the lung and nasopharyngeal microbiome is altered in patients with asthma and allergic rhinitis. While these results are interesting, the underlying mechanisms are still unclear and need to be investigated with functional studies. This review gives a short overview of the terminology and methods used in microbiome research before highlighting results concerning the lung, skin, and intestinal microbiome in allergic diseases.}, }
@article {pmid34224290, year = {2021}, author = {Saha, D and Ota, MOC and Pereira, P and Buchy, P and Badur, S}, title = {Rotavirus vaccines performance: dynamic interdependence of host, pathogen and environment.}, journal = {Expert review of vaccines}, volume = {20}, number = {8}, pages = {945-957}, doi = {10.1080/14760584.2021.1951247}, pmid = {34224290}, issn = {1744-8395}, mesh = {Child ; Diarrhea ; Humans ; Infant ; *Rotavirus ; *Rotavirus Infections/epidemiology/prevention &amp; control ; *Rotavirus Vaccines ; Vaccination/methods ; }, abstract = {INTRODUCTION: As of January 2021, rotavirus vaccination programs have been implemented in 109 countries and their use has resulted in a positive impact on rotavirus-related diarrheal hospitalizations and mortality in children below 5 years of age. Despite these successes, several countries in Africa and Asia where disease burden is high have not yet implemented rotavirus vaccination at all or at a scale sufficient enough to demonstrate impact. This could be, among other reasons, due to poor vaccine coverage and the modest levels of efficacy and effectiveness of the vaccines in these resource-limited settings.<br><br>AREAS COVERED: We review various factors related to the human host (malnutrition, maternally derived antibodies and breastfeeding, genetic factors, blood group, and co-administration with oral polio vaccine), rotavirus pathogen (force of infection, strain diversity and coinfections), and the environment (related to the human microbiome) which reflect complex and interconnected processes leading to diminished vaccine performance in resource-limited settings.<br><br>EXPERT OPINION: Addressing the limiting factors for vaccine efficacy is needed but likely to take a long time to be resolved. An immediate solution is to increase the immunization coverage to higher values generating an overall effect of adequate proportion of protected population to reduce the prevalence of rotavirus disease.}, }
@article {pmid34222331, year = {2021}, author = {DiMucci, D and Kon, M and Segrè, D}, title = {BowSaw: Inferring Higher-Order Trait Interactions Associated With Complex Biological Phenotypes.}, journal = {Frontiers in molecular biosciences}, volume = {8}, number = {}, pages = {663532}, pmid = {34222331}, issn = {2296-889X}, abstract = {Machine learning is helping the interpretation of biological complexity by enabling the inference and classification of cellular, organismal and ecological phenotypes based on large datasets, e.g., from genomic, transcriptomic and metagenomic analyses. A number of available algorithms can help search these datasets to uncover patterns associated with specific traits, including disease-related attributes. While, in many instances, treating an algorithm as a black box is sufficient, it is interesting to pursue an enhanced understanding of how system variables end up contributing to a specific output, as an avenue toward new mechanistic insight. Here we address this challenge through a suite of algorithms, named BowSaw, which takes advantage of the structure of a trained random forest algorithm to identify combinations of variables ("rules") frequently used for classification. We first apply BowSaw to a simulated dataset and show that the algorithm can accurately recover the sets of variables used to generate the phenotypes through complex Boolean rules, even under challenging noise levels. We next apply our method to data from the integrative Human Microbiome Project and find previously unreported high-order combinations of microbial taxa putatively associated with Crohn's disease. By leveraging the structure of trees within a random forest, BowSaw provides a new way of using decision trees to generate testable biological hypotheses.}, }
@article {pmid34213763, year = {2022}, author = {Hu, J and Wang, C and Blaser, MJ and Li, H}, title = {Joint modeling of zero-inflated longitudinal proportions and time-to-event data with application to a gut microbiome study.}, journal = {Biometrics}, volume = {78}, number = {4}, pages = {1686-1698}, pmid = {34213763}, issn = {1541-0420}, support = {R01 CA159036/CA/NCI NIH HHS/United States ; R01 DK110014/DK/NIDDK NIH HHS/United States ; U01 AI122285/AI/NIAID NIH HHS/United States ; P20 CA252728/CA/NCI NIH HHS/United States ; R01 DK090989/DK/NIDDK NIH HHS/United States ; }, mesh = {Humans ; *Gastrointestinal Microbiome ; Models, Statistical ; *Microbiota ; Linear Models ; Longitudinal Studies ; }, abstract = {Recent studies have suggested that the temporal dynamics of the human microbiome may have associations with human health and disease. An increasing number of longitudinal microbiome studies, which record time to disease onset, aim to identify candidate microbes as biomarkers for prognosis. Owing to the ultra-skewness and sparsity of microbiome proportion (relative abundance) data, directly applying traditional statistical methods may result in substantial power loss or spurious inferences. We propose a novel joint modeling framework [JointMM], which is comprised of two sub-models: a longitudinal sub-model called zero-inflated scaled-beta generalized linear mixed-effects regression to depict the temporal structure of microbial proportions among subjects; and a survival sub-model to characterize the occurrence of an event and its relationship with the longitudinal microbiome proportions. JointMM is specifically designed to handle the zero-inflated and highly skewed longitudinal microbial proportion data and examine whether the temporal pattern of microbial presence and/or the nonzero microbial proportions are associated with differences in the time to an event. The longitudinal sub-model of JointMM also provides the capacity to investigate how the (time-varying) covariates are related to the temporal microbial presence/absence patterns and/or the changing trend in nonzero proportions. Comprehensive simulations and real data analyses are used to assess the statistical efficiency and interpretability of JointMM.}, }
@article {pmid34213529, year = {2021}, author = {Sharma, D and Xu, W}, title = {phyLoSTM: a novel deep learning model on disease prediction from longitudinal microbiome data.}, journal = {Bioinformatics (Oxford, England)}, volume = {37}, number = {21}, pages = {3707-3714}, doi = {10.1093/bioinformatics/btab482}, pmid = {34213529}, issn = {1367-4811}, mesh = {Infant, Newborn ; Humans ; *Deep Learning ; Neural Networks, Computer ; *Microbiota ; *Food Hypersensitivity ; }, abstract = {MOTIVATION: Research shows that human microbiome is highly dynamic on longitudinal timescales, changing dynamically with diet, or due to medical interventions. In this article, we propose a novel deep learning framework 'phyLoSTM', using a combination of Convolutional Neural Networks and Long Short Term Memory Networks (LSTM) for feature extraction and analysis of temporal dependency in longitudinal microbiome sequencing data along with host's environmental factors for disease prediction. Additional novelty in terms of handling variable timepoints in subjects through LSTMs, as well as, weight balancing between imbalanced cases and controls is proposed.<br><br>RESULTS: We simulated 100 datasets across multiple time points for model testing. To demonstrate the model's effectiveness, we also implemented this novel method into two real longitudinal human microbiome studies: (i) DIABIMMUNE three country cohort with food allergy outcomes (Milk, Egg, Peanut and Overall) and (ii) DiGiulio study with preterm delivery as outcome. Extensive analysis and comparison of our approach yields encouraging performance with an AUC of 0.897 (increased by 5%) on simulated studies and AUCs of 0.762 (increased by 19%) and 0.713 (increased by 8%) on the two real longitudinal microbiome studies respectively, as compared to the next best performing method, Random Forest. The proposed methodology improves predictive accuracy on longitudinal human microbiome studies containing spatially correlated data, and evaluates the change of microbiome composition contributing to outcome prediction.<br><br>https://github.com/divya031090/phyLoSTM.<br><br>SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.}, }
@article {pmid34212720, year = {2021}, author = {Pultar, F and Hansen, ME and Wolfrum, S and Böselt, L and Fróis-Martins, R and Bloch, S and Kravina, AG and Pehlivanoglu, D and Schäffer, C and LeibundGut-Landmann, S and Riniker, S and Carreira, EM}, title = {Mutanobactin D from the Human Microbiome: Total Synthesis, Configurational Assignment, and Biological Evaluation.}, journal = {Journal of the American Chemical Society}, volume = {143}, number = {27}, pages = {10389-10402}, doi = {10.1021/jacs.1c04825}, pmid = {34212720}, issn = {1520-5126}, support = {W 1224/FWF_/Austrian Science Fund FWF/Austria ; }, mesh = {Antifungal Agents/chemistry/*pharmacology ; Candida albicans/drug effects ; Hyphae/drug effects ; Models, Molecular ; *Peptides, Cyclic/chemical synthesis/chemistry/pharmacology ; }, abstract = {Mutanobactin D is a non-ribosomal, cyclic peptide isolated from Streptococcus mutans and shows activity reducing yeast-to-hyphae transition as well as biofilm formation of the pathogenic yeast Candida albicans. We report the first total synthesis of this natural product, which relies on enantioselective, zinc-mediated 1,3-dipolar cycloaddition and a sequence of cascading reactions, providing the key lipidated γ-amino acid found in mutanobactin D. The synthesis enables configurational assignment, determination of the dominant solution-state structure, and studies to assess the stability of the lipopeptide substructure found in the natural product. The information stored in the fingerprint region of the IR spectra in combination with quantum chemical calculations proved key to distinguishing between epimers of the α-substituted β-keto amide. Synthetic mutanobactin D drives discovery and analysis of its effect on growth of other members of the human oral consortium. Our results showcase how total synthesis is central for elucidating the complex network of interspecies communications of human colonizers.}, }
@article {pmid34207623, year = {2021}, author = {Déjean, G and Tudela, H and Bruno, L and Kissi, D and Rawadi, G and Claus, SP}, title = {Identifying a Novel Bile Salt Hydrolase from the Keystone Gut Bacterium Christensenella minuta.}, journal = {Microorganisms}, volume = {9}, number = {6}, pages = {}, pmid = {34207623}, issn = {2076-2607}, abstract = {Christensenella minuta are human gut dwelling bacteria that have been proposed as key members of the gut microbiome, regulating energy balance and adiposity of their host. We formerly identified that a novel strain of C. minuta (strain DSM33407) boosted microbiota diversity and stimulated deconjugation of the primary bile acid taurocholic acid in human samples. However, there is no description of a bile salt hydrolase (BSH) protein carried in the genome of C. minuta. Here, we identified and cloned a protein from C. minuta's genome that carries a potent BSH activity, which preferentially deconjugates glycine-conjugated bile acids. We then retrieved 14,319 putative BSH sequences from the NCBI database and filtered them using the UHGP database to collect a total of 6701 sequences that were used to build the most comprehensive phylogenetic tree of BSH-related enzymes identified in the human microbiome so far. This phylogenetic tree revealed that C. minuta's BSH amino acid sequence clusters away from others with a threshold of 70% identity. This is therefore the first description of C. minuta's BSH protein, which may be involved in its unique role within the human gut microbial ecosystem.}, }
@article {pmid34206965, year = {2021}, author = {Rebelo, JS and Domingues, CPF and Dionisio, F and Gomes, MC and Botelho, A and Nogueira, T}, title = {COVID-19 Lockdowns May Reduce Resistance Genes Diversity in the Human Microbiome and the Need for Antibiotics.}, journal = {International journal of molecular sciences}, volume = {22}, number = {13}, pages = {}, pmid = {34206965}, issn = {1422-0067}, support = {PTDC/BIA-MIC/28824/2017//Funda&#xe7;&#xe3;o para a Ci&#xea;ncia e a Tecnologia/ ; UIDP/00329/2020//Funda&#xe7;&#xe3;o para a Ci&#xea;ncia e a Tecnologia/ ; }, mesh = {Algorithms ; Anti-Bacterial Agents/*pharmacology/therapeutic use ; Bacterial Infections/drug therapy ; COVID-19/pathology/virology ; Databases, Factual ; Drug Resistance, Microbial/*drug effects/genetics ; *Genetic Variation ; Humans ; Physical Distancing ; Quarantine ; SARS-CoV-2/isolation &amp; purification ; }, abstract = {Recently, much attention has been paid to the COVID-19 pandemic. Yet bacterial resistance to antibiotics remains a serious and unresolved public health problem that kills hundreds of thousands of people annually, being an insidious and silent pandemic. To contain the spreading of the SARS-CoV-2 virus, populations confined and tightened hygiene measures. We performed this study with computer simulations and by using mobility data of mobile phones from Google in the region of Lisbon, Portugal, comprising 3.7 million people during two different lockdown periods, scenarios of 40 and 60% mobility reduction. In the simulations, we assumed that the network of physical contact between people is that of a small world and computed the antibiotic resistance in human microbiomes after 180 days in the simulation. Our simulations show that reducing human contacts drives a reduction in the diversity of antibiotic resistance genes in human microbiomes. Kruskal-Wallis and Dunn's pairwise tests show very strong evidence (p < 0.000, adjusted using the Bonferroni correction) of a difference between the four confinement regimes. The proportion of variability in the ranked dependent variable accounted for by the confinement variable was η[2] = 0.148, indicating a large effect of confinement on the diversity of antibiotic resistance. We have shown that confinement and hygienic measures, in addition to reducing the spread of pathogenic bacteria in a human network, also reduce resistance and the need to use antibiotics.}, }
@article {pmid34202495, year = {2021}, author = {Woods, DF and Flynn, S and Caparrós-Martín, JA and Stick, SM and Reen, FJ and O'Gara, F}, title = {Systems Biology and Bile Acid Signalling in Microbiome-Host Interactions in the Cystic Fibrosis Lung.}, journal = {Antibiotics (Basel, Switzerland)}, volume = {10}, number = {7}, pages = {}, pmid = {34202495}, issn = {2079-6382}, support = {EU-634486//European Commission/ ; SSPC-2/PharM5/SFI_/Science Foundation Ireland/Ireland ; 13/TIDA/B2625/SFI_/Science Foundation Ireland/Ireland ; 14/TIDA/2438/SFI_/Science Foundation Ireland/Ireland ; 15/TIDA/2977/SFI_/Science Foundation Ireland/Ireland ; MRCG-2014-6/HRBI_/Health Research Board/Ireland ; MRCG-2018-16/HRBI_/Health Research Board/Ireland ; ILP-POR-2019-004/HRBI_/Health Research Board/Ireland ; 2017//The Glenn Brown Memorial Grant/ ; Grant CFF 1710//Cystic Fibrosis Foundation/ ; Synergy APP1183640//Australian NHMRC 2020/ ; }, abstract = {The study of the respiratory microbiota has revealed that the lungs of healthy and diseased individuals harbour distinct microbial communities. Imbalances in these communities can contribute to the pathogenesis of lung disease. How these imbalances occur and establish is largely unknown. This review is focused on the genetically inherited condition of Cystic Fibrosis (CF). Understanding the microbial and host-related factors that govern the establishment of chronic CF lung inflammation and pathogen colonisation is essential. Specifically, dissecting the interplay in the inflammation-pathogen-host axis. Bile acids are important host derived and microbially modified signal molecules that have been detected in CF lungs. These bile acids are associated with inflammation and restructuring of the lung microbiota linked to chronicity. This community remodelling involves a switch in the lung microbiota from a high biodiversity/low pathogen state to a low biodiversity/pathogen-dominated state. Bile acids are particularly associated with the dominance of Proteobacterial pathogens. The ability of bile acids to impact directly on both the lung microbiota and the host response offers a unifying principle underpinning the pathogenesis of CF. The modulating role of bile acids in lung microbiota dysbiosis and inflammation could offer new potential targets for designing innovative therapeutic approaches for respiratory disease.}, }
@article {pmid34201752, year = {2021}, author = {Yan, R and Andrew, L and Marlow, E and Kunaratnam, K and Devine, A and Dunican, IC and Christophersen, CT}, title = {Dietary Fibre Intervention for Gut Microbiota, Sleep, and Mental Health in Adults with Irritable Bowel Syndrome: A Scoping Review.}, journal = {Nutrients}, volume = {13}, number = {7}, pages = {}, pmid = {34201752}, issn = {2072-6643}, mesh = {Dietary Fiber/*therapeutic use ; *Gastrointestinal Microbiome ; Humans ; Irritable Bowel Syndrome/*microbiology/physiopathology/psychology/*therapy ; *Mental Health ; Sleep/*physiology ; Treatment Outcome ; }, abstract = {Irritable bowel syndrome (IBS) is a common functional gastrointestinal disorder affecting 4-5% of the global population. This disorder is associated with gut microbiota, diet, sleep, and mental health. This scoping review therefore aims to map existing research that has administrated fibre-related dietary intervention to IBS individuals and reported outcomes on at least two of the three following themes: gut microbiota, sleep, and mental health. Five digital databases were searched to identify and select papers as per the inclusion and exclusion criteria. Five articles were included in the assessment, where none reported on all three themes or the combination of gut microbiota and sleep. Two studies identified alterations in gut microbiota and mental health with fibre supplementation. The other three studies reported on mental health and sleep outcomes using subjective questionnaires. IBS-related research lacks system biology-type studies targeting gut microbiota, sleep, and mental health in patients undergoing diet intervention. Further IBS research is required to explore how human gut microbiota functions (such as short-chain fatty acids) in sleep and mental health, following the implementation of dietary pattern alteration or component supplementation. Additionally, the application of objective sleep assessments is required in order to detect sleep change with more accuracy and less bias.}, }
@article {pmid34200572, year = {2021}, author = {Dereschuk, K and Apostol, L and Ranjan, I and Chakladar, J and Li, WT and Rajasekaran, M and Chang, EY and Ongkeko, WM}, title = {Identification of Lung and Blood Microbiota Implicated in COVID-19 Prognosis.}, journal = {Cells}, volume = {10}, number = {6}, pages = {}, pmid = {34200572}, issn = {2073-4409}, support = {R00RG2369//Office of the President, University of California/ ; RG096651//University of California, San Diego Academic Senate/ ; }, mesh = {Bronchoalveolar Lavage Fluid/microbiology/virology ; COVID-19/*diagnosis/immunology/microbiology/virology ; Case-Control Studies ; Humans ; Leukocytes, Mononuclear/*microbiology/virology ; Liquid Biopsy ; Lung/*microbiology/pathology/virology ; Microbiota/genetics/immunology/*physiology ; Prognosis ; RNA, Bacterial/analysis ; RNA, Fungal/analysis ; RNA-Seq ; SARS-CoV-2/physiology ; }, abstract = {The implications of the microbiome on Coronavirus disease 2019 (COVID-19) prognosis has not been thoroughly studied. In this study we aimed to characterize the lung and blood microbiome and their implication on COVID-19 prognosis through analysis of peripheral blood mononuclear cell (PBMC) samples, lung biopsy samples, and bronchoalveolar lavage fluid (BALF) samples. In all three tissue types, we found panels of microbes differentially abundant between COVID-19 and normal samples correlated to immune dysregulation and upregulation of inflammatory pathways, including key cytokine pathways such as interleukin (IL)-2, 3, 5-10 and 23 signaling pathways and downregulation of anti-inflammatory pathways including IL-4 signaling. In the PBMC samples, six microbes were correlated with worse COVID-19 severity, and one microbe was correlated with improved COVID-19 severity. Collectively, our findings contribute to the understanding of the human microbiome and suggest interplay between our identified microbes and key inflammatory pathways which may be leveraged in the development of immune therapies for treating COVID-19 patients.}, }
@article {pmid34193273, year = {2021}, author = {Bacci, G and Mengoni, A and Emiliani, G and Chiellini, C and Cipriani, EG and Bianconi, G and Canganella, F and Fani, R}, title = {Defining the resilience of the human salivary microbiota by a 520-day longitudinal study in a confined environment: the Mars500 mission.}, journal = {Microbiome}, volume = {9}, number = {1}, pages = {152}, pmid = {34193273}, issn = {2049-2618}, support = {I/011/11/0//Agenzia Spaziale Italiana (IT)/ ; }, mesh = {Diet ; Humans ; Longitudinal Studies ; *Microbiota ; RNA, Ribosomal, 16S/genetics ; *Space Flight ; }, abstract = {BACKGROUND: The human microbiota plays several roles in health and disease but is often difficult to determine which part is in intimate relationships with the host vs. the occasional presence. During the Mars500 mission, six crewmembers lived completely isolated from the outer world for 520 days following standardized diet regimes. The mission constitutes the first spaceflight simulation to Mars and was a unique experiment to determine, in a longitudinal study design, the composition and importance of the resident vs. a more variable microbiota-the fraction of the human microbiota that changes in time and according to environmental conditions-in humans.<br><br>METHODS: Here, we report the characterization of the salivary microbiota from 88 samples taken during and after Mars500 mission for a total of 720 days. Amplicon sequencing of the V3-V4 regions of 16S rRNA gene was performed, and results were analyzed monitoring the diversity of the microbiota while evaluating the effect of the three main variables present in the experimental system: time, diet, and individuality of each subject.<br><br>RESULTS: Results showed statistically significant effects for either time, diet, and individuality of each subject. The main contribution came from the individuality of each subject, emphasizing salivary microbiota-personalized features, and an individual-based resilience of the microbiota.<br><br>CONCLUSIONS: The uniqueness of Mars500 mission, allowed to dampen the effect of environmental variables on salivary microbiota, highlighting its pronounced personalization even after sharing the same physical space for more than a year. Video abstract.}, }
@article {pmid34184753, year = {2022}, author = {Seegers, JFML and Gül, IS and Hofkens, S and Brosel, S and Schreib, G and Brenke, J and Donath, C and de Vos, WM}, title = {Toxicological safety evaluation of live Anaerobutyricum soehngenii strain CH106.}, journal = {Journal of applied toxicology : JAT}, volume = {42}, number = {2}, pages = {244-257}, pmid = {34184753}, issn = {1099-1263}, mesh = {Animals ; Clostridiales/*physiology ; Female ; Male ; Mutagenicity Tests ; Probiotics/*toxicity ; Rats ; Specific Pathogen-Free Organisms ; Toxicity Tests, Subchronic ; }, abstract = {The gut commensal Anaerobutyricum soehngenii is an anaerobe that can produce both propionate and butyrate, metabolites that have been shown to have a positive effect on gut and overall health. Murine and human dose finding studies have shown that oral intake of A. soehngenii has a positive influence on peripheral insulin resistance, thereby reducing the risk of type 2 diabetes. A recent human intervention provided support for the mode of action of A. soehngenii as it affected gene expression in the duodenum, stimulated the secretion of GLP-1 and improved insulin sensitivity. For these reasons A. soehngenii has been proposed as a food ingredient. Before introducing this bacterium to the food chain, however, it must be established that oral intake of live A. soehngenii bacteria does not pose any health risk. As part of the safety analysis of A. soehngenii strain CH106, we performed genotoxicity assays to determine its mutagenic potential (bacterial reverse mutation and in vitro mammalian cell micronucleus tests) and a 90-day subchronic toxicity study in rats to determine overall toxicity potential. The results of both genotoxicity studies were negative, showing no genotoxic effects. For the 90-day subchronic toxicity study, no adverse events were registered that could be attributed to the feeding with A. soehngenii strain CH106. Even at the highest dose, which exceeds the expected daily human intake more than 100-fold, no adverse events were observed. These result support the conclusion that the use of A. soehngenii strain CH106 as a food ingredient is safe.}, }
@article {pmid34178459, year = {2021}, author = {Jacobson, D and Moore, K and Gunderson, C and Rowland, M and Austin, R and Honap, TP and Xu, J and Warinner, C and Sankaranarayanan, K and Lewis, CM}, title = {Shifts in gut and vaginal microbiomes are associated with cancer recurrence time in women with ovarian cancer.}, journal = {PeerJ}, volume = {9}, number = {}, pages = {e11574}, pmid = {34178459}, issn = {2167-8359}, support = {R01 GM089886/GM/NIGMS NIH HHS/United States ; }, abstract = {Many studies investigating the human microbiome-cancer interface have focused on the gut microbiome and gastrointestinal cancers. Outside of human papillomavirus driving cervical cancer, little is known about the relationship between the vaginal microbiome and other gynecological cancers, such as ovarian cancer. In this retrospective study, we investigated the relationship between ovarian cancer, platinum-free interval (PFI) length, and vaginal and gut microbiomes. We observed that Lactobacillus-dominated vaginal communities were less common in women with ovarian cancer, as compared to existing datasets of similarly aged women without cancer. Primary platinum-resistance (PPR) disease is strongly associated with survivability under one year, and we found over one-third of patients with PPR (PFI < 6 months, n = 17) to have a vaginal microbiome dominated by Escherichia (>20% relative abundance), while only one platinum super-sensitive (PFI > 24 months, n = 23) patient had an Escherichia-dominated microbiome. Additionally, L. iners was associated with little, or no, gross residual disease, while other Lactobacillus species were dominant in women with >1 cm gross residual disease. In the gut microbiome, we found patients with PPR disease to have lower phylogenetic diversity than platinum-sensitive patients. The trends we observe in women with ovarian cancer and PPR disease, such as the absence of Lactobacillus and presence of Escherichia in the vaginal microbiome as well as low gut microbiome phylogenetic diversity have all been linked to other diseases and/or pro-inflammatory states, including bacterial vaginosis and autoimmune disorders. Future prospective studies are necessary to explore the translational potential and underlying mechanisms driving these associations.}, }
@article {pmid34176489, year = {2021}, author = {Berry, ASF and Pierdon, MK and Misic, AM and Sullivan, MC and O'Brien, K and Chen, Y and Murray, SJ and Ramharack, LA and Baldassano, RN and Parsons, TD and Beiting, DP}, title = {Remodeling of the maternal gut microbiome during pregnancy is shaped by parity.}, journal = {Microbiome}, volume = {9}, number = {1}, pages = {146}, pmid = {34176489}, issn = {2049-2618}, support = {4100068710//Commonwealth Universal Research Enhancement (CURE) program/ ; }, mesh = {Animals ; Female ; *Gastrointestinal Microbiome ; Parity ; Pregnancy ; *Premature Birth ; Prevotella ; Swine ; Treponema ; }, abstract = {BACKGROUND: The maternal microbiome has emerged as an important factor in gestational health and outcome and is associated with risk of preterm birth and offspring morbidity. Epidemiological evidence also points to successive pregnancies-referred to as maternal parity-as a risk factor for preterm birth, infant mortality, and impaired neonatal growth. Despite the fact that both the maternal microbiome and parity are linked to maternal-infant health, the impact of parity on the microbiome remains largely unexplored, in part due to the challenges of studying parity in humans.<br><br>RESULTS: Using synchronized pregnancies and dense longitudinal monitoring of the microbiome in pigs, we describe a microbiome trajectory during pregnancy and determine the extent to which parity modulates this trajectory. We show that the microbiome changes reproducibly during gestation and that this remodeling occurs more rapidly as parity increases. At the time of parturition, parity was linked to the relative abundance of several bacterial species, including Treponema bryantii, Lactobacillus amylovorus, and Lactobacillus reuteri. Strain tracking carried out in 18 maternal-offspring "quadrads"-each consisting of one mother sow and three piglets-linked maternal parity to altered levels of Akkermansia muciniphila, Prevotella stercorea, and Campylobacter coli in the infant gut 10 days after birth.<br><br>CONCLUSIONS: Collectively, these results identify parity as an important environmental factor that modulates the gut microbiome during pregnancy and highlight the utility of a swine model for investigating the microbiome in maternal-infant health. In addition, our data show that the impact of parity extends beyond the mother and is associated with alterations in the community of bacteria that colonize the offspring gut early in life. The bacterial species we identified as parity-associated in the mother and offspring have been shown to influence host metabolism in other systems, raising the possibility that such changes may influence host nutrient acquisition or utilization. These findings, taken together with our observation that even subtle differences in parity are associated with microbiome changes, underscore the importance of considering parity in the design and analysis of human microbiome studies during pregnancy and in infants. Video abstract.}, }
@article {pmid34169332, year = {2022}, author = {Djemai, K and Drancourt, M and Tidjani Alou, M}, title = {Bacteria and Methanogens in the Human Microbiome: a Review of Syntrophic Interactions.}, journal = {Microbial ecology}, volume = {83}, number = {3}, pages = {536-554}, pmid = {34169332}, issn = {1432-184X}, support = {M&#xe9;diterran&#xe9;e Infection 10-IAHU-03//National Research Agency/ ; }, mesh = {Archaea/metabolism ; Bacteria/genetics/metabolism ; *Euryarchaeota/metabolism ; Humans ; Methane/metabolism ; *Microbiota ; }, abstract = {Methanogens are microorganisms belonging to the Archaea domain and represent the primary source of biotic methane. Methanogens encode a series of enzymes which can convert secondary substrates into methane following three major methanogenesis pathways. Initially recognized as environmental microorganisms, methanogens have more recently been acknowledged as host-associated microorganisms after their detection and initial isolation in ruminants in the 1950s. Methanogens have also been co-detected with bacteria in various pathological situations, bringing their role as pathogens into question. Here, we review reported associations between methanogens and bacteria in physiological and pathological situations in order to understand the metabolic interactions explaining these associations. To do so, we describe the origin of the metabolites used for methanogenesis and highlight the central role of methanogens in the syntrophic process during carbon cycling. We then focus on the metabolic abilities of co-detected bacterial species described in the literature and infer from their genomes the probable mechanisms of their association with methanogens. The syntrophic interactions between bacteria and methanogens are paramount to gut homeostasis. Therefore, any dysbiosis affecting methanogens might impact human health. Thus, the monitoring of methanogens may be used as a bio-indicator of dysbiosis. Moreover, new therapeutic approaches can be developed based on their administration as probiotics. We thus insist on the importance of investigating methanogens in clinical microbiology.}, }
@article {pmid34162397, year = {2021}, author = {Zozaya-Valdés, E and Wong, SQ and Raleigh, J and Hatzimihalis, A and Ftouni, S and Papenfuss, AT and Sandhu, S and Dawson, MA and Dawson, SJ}, title = {Detection of cell-free microbial DNA using a contaminant-controlled analysis framework.}, journal = {Genome biology}, volume = {22}, number = {1}, pages = {187}, pmid = {34162397}, issn = {1474-760X}, mesh = {Bacteroides/classification/genetics/isolation &amp; purification ; Cell-Free Nucleic Acids/blood/*genetics ; DNA Contamination ; DNA, Bacterial/blood/*genetics ; Faecalibacterium/classification/genetics/isolation &amp; purification ; Feces/microbiology ; Humans ; Melanoma/diagnosis/*microbiology/pathology ; Microbiota/*genetics ; Neoplasm Metastasis ; Neoplasm Staging ; Polymerase Chain Reaction/methods ; RNA, Ribosomal, 16S/genetics ; Ruminococcus/classification/genetics/isolation &amp; purification ; Saliva/microbiology ; Skin Neoplasms/diagnosis/*microbiology/pathology ; Symbiosis/physiology ; }, abstract = {BACKGROUND: The human microbiome plays an important role in cancer. Accumulating evidence indicates that commensal microbiome-derived DNA may be represented in minute quantities in the cell-free DNA of human blood and could possibly be harnessed as a new cancer biomarker. However, there has been limited use of rigorous experimental controls to account for contamination, which invariably affects low-biomass microbiome studies.<br><br>RESULTS: We apply a combination of 16S-rRNA-gene sequencing and droplet digital PCR to determine if the specific detection of cell-free microbial DNA (cfmDNA) is possible in metastatic melanoma patients. Compared to matched stool and saliva samples, the absolute concentration of cfmDNA is low but significantly above the levels detected from negative controls. The microbial community of plasma is strongly influenced by laboratory and reagent contaminants introduced during the DNA extraction and sequencing processes. Through the application of an in silico decontamination strategy including the filtering of amplicon sequence variants (ASVs) with batch dependent abundances and those with a higher prevalence in negative controls, we identify known gut commensal bacteria, such as Faecalibacterium, Bacteroides and Ruminococcus, and also other uncharacterised ASVs. We analyse additional plasma samples, highlighting the potential of this framework to identify differences in cfmDNA between healthy and cancer patients.<br><br>CONCLUSIONS: Together, these observations indicate that plasma can harbour a low yet detectable level of cfmDNA. The results highlight the importance of accounting for contamination and provide an analytical decontamination framework to allow the accurate detection of cfmDNA for future biomarker studies in cancer and other diseases.}, }
@article {pmid34161373, year = {2021}, author = {Yamamoto, S and Saito, M and Tamura, A and Prawisuda, D and Mizutani, T and Yotsuyanagi, H}, title = {The human microbiome and COVID-19: A systematic review.}, journal = {PloS one}, volume = {16}, number = {6}, pages = {e0253293}, pmid = {34161373}, issn = {1932-6203}, mesh = {Bronchoalveolar Lavage Fluid ; COVID-19/*microbiology ; Dysbiosis/*microbiology/virology ; Feces/microbiology ; Gastrointestinal Microbiome ; Humans ; *Microbiota ; Nasopharynx/*microbiology ; }, abstract = {BACKGROUND: Human microbiotas are communities of microorganisms living in symbiosis with humans. They play an important role in the host immune response to respiratory viral infection. However, evidence on the human microbiome and coronavirus disease (COVID-19) relationship is insufficient. The aim of this systematic literature review was to evaluate existing evidence on the association between the microbiome and COVID-19 in humans and summarize these data in the pandemic era.<br><br>METHODS: We conducted a systematic literature review on the association between the microbiome and COVID-19 in humans by searching PubMed, Embase, and the Cochrane Library, CINAHL, and Web of Science databases for articles in English published up to October 31, 2020. The results were analyzed qualitatively. This study is registered with PROSPERO (CRD42020195982).<br><br>RESULTS: Of the 543 articles identified by searching databases, 16 in line with the research objectives were eligible for qualitative review: eight sampled the microbiome using stool, four using nasopharyngeal or throat swab, three using bronchoalveolar lavage fluid, and one using lung tissue. Fecal microbiome dysbiosis and increased opportunistic pathogens were reported in COVID-19 patients. Several studies suggested the dysbiosis in the lung microbiome of COVID-19 patients with an abundance of opportunistic pathogens using lower respiratory tract samples. The association between COVID-19 severity and the human microbiome remains uncertain.<br><br>CONCLUSION: The human fecal and respiratory tract microbiome changed in COVID-19 patients with opportunistic pathogen abundance. Further research to elucidate the effect of alternation of the human microbiome in disease pathogenesis is warranted.}, }
@article {pmid34156021, year = {2021}, author = {Koval, TV and Chopey, IV and Hechko, MM and Kurakh, AV}, title = {NON-ALCOHOLIC FATTY LIVER DISEASE IN THE CONTEXT OF ALTERED GUT MICROBIOTA.}, journal = {Wiadomosci lekarskie (Warsaw, Poland : 1960)}, volume = {74}, number = {4}, pages = {1007-1010}, pmid = {34156021}, issn = {0043-5147}, mesh = {*Gastrointestinal Microbiome ; Humans ; *Microbiota ; *Non-alcoholic Fatty Liver Disease/etiology ; }, abstract = {OBJECTIVE: The aim: To analyze the relationship between non-alcoholic fatty liver disease and changes in the gut microbiota.<br><br>PATIENTS AND METHODS: Materials and methods: The publications of domestic and foreign editions in the databases of the United European Gastroenterology (UEG) Journal, PubMed, MEDLINE, Web of Science were processed and analyzed.<br><br>CONCLUSION: Conclusions: In recent years, non-alcoholic fatty liver disease was placed among the important diseases in gastroenterology. During this time, more and more data appear on the link between changes in the human intestinal microbiome and the development of metabolic diseases, including NAFLD. Contemporary research has indeed found evidence of such a relationship. Thus, some strains of microorganisms have been identified in more detail, which directly or indirectly affect the development or course of the above-mentioned disease. For a better understanding of the strategies for the treatment of pathologies, it is necessary to delve into the study of etiological factors, therefore, NAFLC cannot be considered a pathology that has been sufficiently studied. Indeed, recent data indicate that the development and severity of the course of the disease are not always associated with the physiological processes already known to us.}, }
@article {pmid34151446, year = {2021}, author = {Adler, CJ and Cao, KL and Hughes, T and Kumar, P and Austin, C}, title = {How does the early life environment influence the oral microbiome and determine oral health outcomes in childhood?.}, journal = {BioEssays : news and reviews in molecular, cellular and developmental biology}, volume = {43}, number = {9}, pages = {e2000314}, pmid = {34151446}, issn = {1521-1878}, support = {R01 DE029838/DE/NIDCR NIH HHS/United States ; 1R01DE029838-01/DE/NIDCR NIH HHS/United States ; }, mesh = {Child, Preschool ; *Dental Caries ; Environmental Exposure/analysis ; *Exposome ; Female ; Humans ; *Microbiota ; Outcome Assessment, Health Care ; Pregnancy ; }, abstract = {The first 1000 days of life, from conception to 2 years, are a critical window for the influence of environmental exposures on the assembly of the oral microbiome, which is the precursor to dental caries (decay), one of the most prevalent microbially induced disorders worldwide. While it is known that the human microbiome is susceptible to environmental exposures, there is limited understanding of the impact of prenatal and early childhood exposures on the oral microbiome trajectory and oral health. A barrier has been the lack of technology to directly measure the foetal "exposome", which includes nutritional and toxic exposures crossing the placenta. Another barrier has been the lack of statistical methods to account for the high dimensional data generated by-omic assays. Through identifying which early life exposures influence the oral microbiome and modify oral health, these findings can be translated into interventions to reduce dental decay prevalence.}, }
@article {pmid34149649, year = {2021}, author = {Morrison, MD and Thissen, JB and Karouia, F and Mehta, S and Urbaniak, C and Venkateswaran, K and Smith, DJ and Jaing, C}, title = {Investigation of Spaceflight Induced Changes to Astronaut Microbiomes.}, journal = {Frontiers in microbiology}, volume = {12}, number = {}, pages = {659179}, pmid = {34149649}, issn = {1664-302X}, abstract = {The International Space Station (ISS) is a uniquely enclosed environment that has been continuously occupied for the last two decades. Throughout its operation, protecting the health of the astronauts on-board has been a high priority. The human microbiome plays a significant role in maintaining human health, and disruptions in the microbiome have been linked to various diseases. To evaluate the effects of spaceflight on the human microbiome, body swabs and saliva samples were collected from four ISS astronauts on consecutive expeditions. Astronaut samples were analyzed using shotgun metagenomic sequencing and microarrays to characterize the microbial biodiversity before, during, and after the astronauts' time onboard the ISS. Samples were evaluated at an individual and population level to identify changes in microbial diversity and abundance. No significant changes in the number or relative abundance of taxa were observed between collection time points when samples from all four astronauts were analyzed together. When the astronauts' saliva samples were analyzed individually, the saliva samples of some astronauts showed significant changes in the relative abundance of taxa during and after spaceflight. The relative abundance of Prevotella in saliva samples increased during two astronauts' time onboard the ISS while the relative abundance of other commensal taxa such as Neisseria, Rothia, and Haemophilus decreased. The abundance of some antimicrobial resistance genes within the saliva samples also showed significant changes. Most notably, elfamycin resistance gene significantly increased in all four astronauts post-flight and a CfxA6 beta-lactam marker significantly increased during spaceflight but returned to normal levels post-flight. The combination of both shotgun metagenomic sequencing and microarrays showed the benefit of both technologies in monitoring microbes on board the ISS. There were some changes in each astronaut's microbiome during spaceflight, but these changes were not universal for all four astronauts. Two antimicrobial resistance gene markers did show a significant change in abundance in the saliva samples of all four astronauts across their collection times. These results provide insight for future ISS microbial monitoring studies and targets for antimicrobial resistance screenings.}, }
@article {pmid34136418, year = {2021}, author = {de Cena, JA and Zhang, J and Deng, D and Damé-Teixeira, N and Do, T}, title = {Low-Abundant Microorganisms: The Human Microbiome's Dark Matter, a Scoping Review.}, journal = {Frontiers in cellular and infection microbiology}, volume = {11}, number = {}, pages = {689197}, pmid = {34136418}, issn = {2235-2988}, mesh = {Bacteria/genetics ; *Dysbiosis ; Female ; Fungi/genetics ; Humans ; *Microbiota ; Mouth ; }, abstract = {Research on the human microbiome has mainly been restricted to the identification of most abundant microbiota associated with health or disease. Their abundance may reflect their capacity to exploit their niche, however, metabolic functions exerted by low-abundant microrganisms can impact the dysbiotic signature of local microbial habitats. This scoping review aims to map the literature regarding the management of low-abundant microorganisms in studies investigating human microbiome samples. A systematic literature search was performed in 5 electronic databases, as well as grey literature. We selected clinical microbiome studies targeting human participants of any age, from any body site. We also included studies with secondary data which originated from human biofilm samples. All of the papers used next-generation sequencing (NGS) techniques in their methodology. A total of 826 manuscripts were retrieved, of which 42 were included in this review and 22 reported low-abundant bacteria (LB) in samples taken from 7 body sites (breast, gut, oral cavity, skin, stomach, upper respiratory tract (URT), and vagina). Four studies reported microbes at abundance levels between 5 and 20%, 8 studies reported between 1 and 5%, and 18 studies reported below 1%. Fifteen papers mentioned fungi and/or archaea, and from those only 4 (fungi) and 2 (archaea) produced data regarding the abundance of these domains. While most studies were directed towards describing the taxonomy, diversity and abundance of the highly abundant species, low-abundant species have largely been overlooked. Indeed, most studies select a cut-off value at <1% for low-abundant organisms to be excluded in their analyses. This practice may compromise the true diversity and influence of all members of the human microbiota. Despite their low abundance and signature in biofilms, they may generate important markers contributing to dysbiosis, in a sort of 'butterfly effect'. A detailed snapshot of the physiological, biological mechanisms at play, including virulence determinants in the context of a dysbiotic community, may help better understand the health-disease transition.}, }
@article {pmid34136092, year = {2021}, author = {Ma, ZS}, title = {Spatial heterogeneity analysis of the human virome with Taylor's power law.}, journal = {Computational and structural biotechnology journal}, volume = {19}, number = {}, pages = {2921-2927}, pmid = {34136092}, issn = {2001-0370}, abstract = {Spatial heterogeneity is a fundamental characteristic of organisms from viruses to humans. Measuring heterogeneity is challenging, especially for naked-eye invisible viruses, but of obvious importance. For example, spatial heterogeneity of virus distribution may strongly influence infection spreading and outbreaks in the case of pathogenic viruses; the spatial distribution (i.e., the inter-subject heterogeneity) of commensal viruses within/on our bodies can influence the competition, coexistence, and dispersal of viruses within or between our bodies. Taylor's power law (TPL) was first discovered in the 1960s to describe the spatial distributions of plant and/or animal populations, and since then it has been verified by numerous experimental and theoretical studies. Recently, TPL has been extended from population to community level and applied to bacterial communities. Here we report the first comprehensive testing of the TPL fitted to human virome datasets. It was found that the human virome follows the TPL as bacterial communities do. Furthermore, the TPL heterogeneity scaling parameter of human virome is virtually the same as that of the human bacterial microbiome (1.916 vs. 1.926). We postulate that the extreme closeness of human viruses and bacteria in heterogeneity scaling coefficients could be attributed to the fact that most of the viruses that were annotated in this study actually belong to bacteriophages (86% viral OTUs) that "piggyback" on their bacterial hosts, and their distributions are likely host-dependent. The scaling parameter, which measures the inter-subject heterogeneity changes, should be an innate property of human microbiomes including both bacteria and viruses. It is similar to the acceleration coefficient of the gravity (g = 9.8) as specified by Newton's law, which is invariant on the earth. Nevertheless, we caution that our postulation is contingent on an implicit assumption that the proportion of bacteriophages to total virome may not change significantly when more virus species can be identified in future.}, }
@article {pmid34130619, year = {2021}, author = {Nuzzo, A and Van Horn, S and Traini, C and Perry, CR and Dumont, EF and Scangarella-Oman, NE and Gardiner, DF and Brown, JR}, title = {Microbiome recovery in adult females with uncomplicated urinary tract infections in a randomised phase 2A trial of the novel antibiotic gepotidacin (GSK140944).}, journal = {BMC microbiology}, volume = {21}, number = {1}, pages = {181}, pmid = {34130619}, issn = {1471-2180}, support = {HHSO100201300011C//Biomedical Advanced Research and Development Authority/ ; }, mesh = {Acenaphthenes/*administration &amp; dosage/pharmacokinetics ; Adult ; Anti-Bacterial Agents/*administration &amp; dosage/pharmacokinetics ; Bacteria/classification/drug effects/genetics/isolation &amp; purification ; Biodiversity ; Female ; Gastrointestinal Tract/microbiology ; Heterocyclic Compounds, 3-Ring/*administration &amp; dosage/pharmacokinetics ; Humans ; Microbiota/*drug effects ; Middle Aged ; Pharynx/microbiology ; Urinary Tract Infections/*drug therapy/microbiology ; Vagina/microbiology ; }, abstract = {BACKGROUND: With increasing concerns about the impact of frequent antibiotic usage on the human microbiome, it is important to characterize the potential for such effects in early antibiotic drug development clinical trials. In a randomised Phase 2a clinical trial study that evaluated the pharmacokinetics of repeated oral doses of gepotidacin, a first-in-chemical-class triazaacenaphthylene antibiotic with a distinct mechanism of action, in adult females with uncomplicated urinary tract infections for gepotidacin (GSK2140944) we evaluated the potential changes in microbiome composition across multiple time points and body-sites (ClinicalTrials.gov : NCT03568942).<br><br>RESULTS: Samples of gastrointestinal tract (GIT), pharyngeal cavity and vaginal microbiota were collected with consent from 22 patients at three time points relative to the gepotidacin dosing regimen; Day 1 (pre-dose), Day 5 (end of dosing) and Follow-up (Day 28&#x2009;&#xb1;&#x2009;3&#x2009;days). Microbiota composition was determined by DNA sequencing of 16S rRNA gene variable region 4 amplicons. By Day 5, significant changes were observed in the microbiome diversity relative to pre-dose across the tested body-sites. However, by the Follow-up visit, microbiome diversity changes were reverted to compositions comparable to Day 1. The greatest range of microbiome changes by body-site were GIT followed by the pharyngeal cavity then vagina. In Follow-up visit samples we found no statistically significant occurrences of pathogenic taxa.<br><br>CONCLUSION: Our findings suggest that gepotidacin alteration of the human microbiome after 5&#x2009;days of dosing is temporary and rebound to pre-dosing states is evident within the first month post-treatment. We recommend that future antibiotic drug trials include similar exploratory investigations into the duration and context of microbiome modification and recovery.<br><br>TRIAL REGISTRATION: NCT03568942 . Registered 26 June 2018.}, }
@article {pmid34128327, year = {2021}, author = {Salmenkari, H and Korpela, R and Vapaatalo, H}, title = {Renin-angiotensin system in intestinal inflammation-Angiotensin inhibitors to treat inflammatory bowel diseases?.}, journal = {Basic &amp; clinical pharmacology &amp; toxicology}, volume = {129}, number = {3}, pages = {161-172}, doi = {10.1111/bcpt.13624}, pmid = {34128327}, issn = {1742-7843}, support = {//Folkh&#xe4;lsan Research Foundation/ ; //Helsinki University Central Hospital Research Funds/ ; OC0013659//Novo Nordisk Foundation/ ; //Wilhelm och Else Stockmanns Stiftelse/ ; //Finska L&#xe4;kares&#xe4;llskapet, Einar och Karin Stroems Stiftelse/ ; }, mesh = {Angiotensin Receptor Antagonists ; Angiotensin-Converting Enzyme Inhibitors/therapeutic use ; Angiotensins/*antagonists &amp; inhibitors/pharmacology/therapeutic use ; Animals ; Antihypertensive Agents/therapeutic use ; Colitis/drug therapy ; Drug Evaluation, Preclinical ; Fibrosis ; Humans ; Hypertension/drug therapy ; Inflammation/*drug therapy ; Inflammatory Bowel Diseases/complications/*drug therapy ; Mice ; Models, Animal ; Renin-Angiotensin System/*drug effects ; Retrospective Studies ; }, abstract = {Inflammatory bowel diseases (IBDs) are chronic disorders of the gastrointestinal tract, which manifest in recurring gastrointestinal inflammation. The current treatment options of IBD are not curative and are lacking in aspects like prevention of fibrosis. New treatment options are needed to fulfil the unmet needs and provide alternatives to drugs with resistances and side effects. Drugs targeting the renin-angiotensin system (RAS), besides being antihypertensive, also possess anti-inflammatory and antifibrotic properties and could offer an inexpensive alternative to control inflammation and fibrosis in the gut. RAS inhibitors have been effective in preventing and alleviating colitis in preclinical studies, but available human data are still sparse. This review outlines the pathophysiological functions of RAS in the gut and summarizes preclinical studies utilizing pharmacological RAS inhibitors in the treatment of experimental colitis. We discuss the alterations in intestinal RAS and the available evidence of the benefits of RAS inhibitors for IBD patients. Retrospective studies comparing IBD patients using ACE inhibitors or angiotensin II receptor blockers have provided optimistic results regarding a milder disease course and fewer hospitalizations and corticosteroid use in patients using RAS inhibitors. Prospective studies are needed to evaluate the effectiveness of these promising medications in the treatment of IBD.}, }
@article {pmid34114375, year = {2021}, author = {Priskorn, L and Tøttenborg, SS and Almstrup, K and Andersson, AM and Axelsson, J and Bräuner, EV and Elenkov, A and Freiesleben, NC and Giwercman, YL and Grøndahl, ML and Hansen, AH and Hansen, LS and Henic, E and Kitlinski, ML and Landersoe, SK and Lindh, C and Løkkegaard, EL and Malm, J and Olsen, KW and Petersen, KU and Schmidt, L and Stormlund, S and Svendsen, PF and Vassard, D and Wang, NF and Zedeler, A and Bhasin, S and Chavarro, J and Eisenberg, ML and Hauser, R and Huhtaniemi, I and Krawetz, SA and Marko-Varga, G and Salonia, A and Toppari, J and Juul, A and Jørgensen, N and Nielsen, HS and Pinborg, A and Rylander, L and Giwercman, A}, title = {RUBIC (ReproUnion Biobank and Infertility Cohort): A binational clinical foundation to study risk factors, life course, and treatment of infertility and infertility-related morbidity.}, journal = {Andrology}, volume = {9}, number = {6}, pages = {1828-1842}, pmid = {34114375}, issn = {2047-2927}, support = {//EU Interreg &#xd6;KS/ ; //Capital Region of Denmark/ ; //Region Sk&#xe5;ne/ ; //Ferring Pharmaceuticals/ ; }, mesh = {Adult ; Biological Specimen Banks ; Biomarkers/analysis ; Denmark ; Female ; Fertility ; Humans ; *Infertility ; Male ; Pregnancy ; Pregnancy Outcome ; *Prospective Studies ; *Reproductive Techniques ; Risk Factors ; Sweden ; }, abstract = {BACKGROUND: Infertility affects 15%-25% of all couples during their reproductive life span. It is a significant societal and public health problem with potential psychological, social, and economic consequences. Furthermore, infertility has been linked to adverse long-term health outcomes. Despite the advanced diagnostic and therapeutic techniques available, approximately 30% of infertile couples do not obtain a live birth after fertility treatment. For these couples, there are no further options to increase their chances of a successful pregnancy and live birth.<br><br>OBJECTIVES: Three overall questions will be studied: (1) What are the risk factors and natural life courses of infertility, early embryonic loss, and adverse pregnancy outcomes? (2) Can we develop new diagnostic and prognostic biomarkers for fecundity and treatment success? And (3) what are the health characteristics of women and men in infertile couples at the time of fertility treatment and during long-term follow-up?<br><br>MATERIAL AND METHODS: ReproUnion Biobank and Infertility Cohort (RUBIC) is established as an add-on to the routine fertility management at Copenhagen University Hospital Departments in the Capital Region of Denmark and Reproductive Medicine Centre at Sk&#xe5;ne University Hospital in Sweden. The aim is to include a total of 5000 couples equally distributed between Denmark and Sweden. The first patients were enrolled in June 2020. All eligible infertile couples are prospectively asked to participate in the project. Participants complete an extensive questionnaire and undergo a physical examination and collection of biospecimens (blood, urine, hair, saliva, rectal swabs, feces, semen, endometrial biopsies, and vaginal swabs). After the cohort is established, the couples will be linked to the Danish and Swedish national registers to obtain information on parental, perinatal, childhood, and adult life histories, including disease and medication history. This will enable us to understand the causes of infertility and identify novel therapeutic options for this important societal problem.}, }
@article {pmid34111601, year = {2021}, author = {Owens, JA and Saeedi, BJ and Naudin, CR and Hunter-Chang, S and Barbian, ME and Eboka, RU and Askew, L and Darby, TM and Robinson, BS and Jones, RM}, title = {Lactobacillus rhamnosus GG Orchestrates an Antitumor Immune Response.}, journal = {Cellular and molecular gastroenterology and hepatology}, volume = {12}, number = {4}, pages = {1311-1327}, pmid = {34111601}, issn = {2352-345X}, support = {T32 DK108735/DK/NIDDK NIH HHS/United States ; F31 CA247415/CA/NCI NIH HHS/United States ; R01 CA179424/CA/NCI NIH HHS/United States ; R01 DK098391/DK/NIDDK NIH HHS/United States ; F30 DK117570/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; CD8-Positive T-Lymphocytes/immunology/metabolism ; Cell Communication ; Colon ; Dendritic Cells/immunology/metabolism ; Disease Models, Animal ; Gastrointestinal Microbiome ; Host Microbial Interactions/immunology ; Humans ; *Immunity ; *Immunomodulation ; Intestinal Mucosa/immunology/metabolism/microbiology/pathology ; Lacticaseibacillus rhamnosus/*immunology ; Mice ; Neoplasms/*immunology/metabolism/pathology/therapy ; Probiotics/administration &amp; dosage ; Signal Transduction ; Toll-Like Receptor 2/metabolism ; Tumor Burden ; }, abstract = {BACKGROUND &amp; AIMS: In colorectal cancer, approximately 95% of patients are refractory to immunotherapy because of low antitumor immune responses. Therefore, there is an exigent need to develop treatments that increase antitumor immune responses and decrease tumor burden to enhance immunotherapy.<br><br>METHODS: The gut microbiome has been described as a master modulator of immune responses. We administered the human commensal, Lactobacillus rhamnosus GG (LGG), to mice and characterized the changes in the gut immune landscape. Because the presence of lactobacilli in the gut microbiome has been linked with decreased tumor burden and antitumor immune responses, we also supplemented a genetic and a chemical model of murine intestinal cancer with LGG. For clinical relevance, we therapeutically administered LGG after tumors had formed. We also tested for the requirement of CD8 T cells in LGG-mediated modulation of gut tumor burden.<br><br>RESULTS: We detected increased colonic CD8 T-cell responses specifically in LGG-supplemented mice. The CD8 T-cell induction was dependent on dendritic cell activation mediated via Toll-like receptor-2, thereby describing a novel mechanism in which a member of the human microbiome induces an intestinal CD8 T-cell response. We also show that LGG decreased tumor burden in the murine gut cancer models by a CD8 T-cell-dependent manner.<br><br>CONCLUSIONS: These data support the potential use of LGG to&#xa0;augment antitumor immune responses in colorectal cancer patients and ultimately for increasing the breadth and efficacy of&#xa0;immunotherapy.}, }
@article {pmid34108237, year = {2022}, author = {Le Roy, T and Moens de Hase, E and Van Hul, M and Paquot, A and Pelicaen, R and Régnier, M and Depommier, C and Druart, C and Everard, A and Maiter, D and Delzenne, NM and Bindels, LB and de Barsy, M and Loumaye, A and Hermans, MP and Thissen, JP and Vieira-Silva, S and Falony, G and Raes, J and Muccioli, GG and Cani, PD}, title = {Dysosmobacter welbionis is a newly isolated human commensal bacterium preventing diet-induced obesity and metabolic disorders in mice.}, journal = {Gut}, volume = {71}, number = {3}, pages = {534-543}, pmid = {34108237}, issn = {1468-3288}, mesh = {Animals ; Case-Control Studies ; Clostridiales/*isolation &amp; purification ; Cohort Studies ; Humans ; Insulin Resistance ; Metabolic Diseases/*microbiology/*prevention &amp; control ; Mice ; Mice, Obese ; Obesity/*microbiology/*prevention &amp; control ; }, abstract = {OBJECTIVE: To investigate the abundance and the prevalence of Dysosmobacter welbionis J115[T], a novel butyrate-producing bacterium isolated from the human gut both in the general population and in subjects with metabolic syndrome. To study the impact of this bacterium on host metabolism using diet-induced obese and diabetic mice.<br><br>DESIGN: We analysed the presence and abundance of the bacterium in 11&#x2009;984 subjects using four human cohorts (ie, Human Microbiome Project, American Gut Project, Flemish Gut Flora Project and Microbes4U). Then, we tested the effects of daily oral gavages with live D. welbionis J115[T] on metabolism and several hallmarks of obesity, diabetes, inflammation and lipid metabolism in obese/diabetic mice.<br><br>RESULTS: This newly identified bacterium was detected in 62.7%-69.8% of the healthy population. Strikingly, in obese humans with a metabolic syndrome, the abundance of Dysosmobacter genus correlates negatively with body mass index, fasting glucose and glycated haemoglobin. In mice, supplementation with live D. welbionis J115[T], but not with the pasteurised bacteria, partially counteracted diet-induced obesity development, fat mass gain, insulin resistance and white adipose tissue hypertrophy and inflammation. In addition, live D. welbionis J115[T] administration protected the mice from brown adipose tissue inflammation in association with increased mitochondria number and non-shivering thermogenesis. These effects occurred with minor impact on the mouse intestinal microbiota composition.<br><br>CONCLUSIONS: These results suggest that D. welbionis J115[T] directly and beneficially influences host metabolism and is a strong candidate for the development of next-generation beneficial bacteria targeting obesity and associated metabolic diseases.}, }
@article {pmid34107988, year = {2021}, author = {Flachs, A and Orkin, JD}, title = {On pickles: biological and sociocultural links between fermented foods and the human gut microbiome.}, journal = {Journal of ethnobiology and ethnomedicine}, volume = {17}, number = {1}, pages = {39}, pmid = {34107988}, issn = {1746-4269}, support = {Global Synergy Grant//College of Liberal Arts, Purdue University/ ; }, mesh = {Fermentation ; *Fermented Foods/microbiology ; *Food Microbiology ; *Gastrointestinal Microbiome ; Humans ; *Microbiota ; }, abstract = {BACKGROUND: The composition of the human microbiome varies considerably in diversity and density across communities as a function of the foods we eat and the places we live. While all foods contain microbes, humans directly shape this microbial ecology through fermentation. Fermented foods are produced from microbial reactions that depend on local environmental conditions, fermentation practices, and the manner in which foods are prepared and consumed. These interactions are of special interest to ethnobiologists because they link investigations of how people shape and know the world around them to local knowledge, food traditions, local flora, and microbial taxa.<br><br>METHODS: In this manuscript, we report on data collected at a fermentation revivalist workshop in Tennessee. To ask how fermentation traditions are learned and influence macro and micro ecologies, we conducted interviews with eleven people and participated in a four-day craft fermentation workshop. We also collected 46 fermented food products and 46 stool samples from workshop participants eating those fermented foods.<br><br>RESULTS: We identified ten major themes comprised of 29 sub-themes drawn from 326 marked codes in the transcripts. In combination, this analysis allowed us to summarize key experiences with fermentation, particularly those related to a sense of authenticity, place, health, and the discovery of tactile work. From the 605 amplicon sequence variants (ASVs) shared between food and fecal samples, we identified 25 candidate ASVs that are suspected to have been transmitted from fermented food samples to the gut microbiomes of the workshop participants. Our results indicate that many of the foods prepared and consumed during the workshop were rich sources of probiotic microbes.<br><br>CONCLUSIONS: By combining these qualitative social and quantitative microbiological data, we suggest that variation in culturally informed fermentation practices introduces variation in bacterial flora even among very similar foods, and that these food products can influence gut microbial ecology.}, }
@article {pmid34102684, year = {2021}, author = {Atzler, M and Westhofen, T and Tamalunas, A and Schott, M and Keller, P and Ebner, B and Stief, C and Magistro, G}, title = {[The role of the microbiome in urological diseases].}, journal = {Aktuelle Urologie}, volume = {52}, number = {4}, pages = {338-344}, doi = {10.1055/a-1478-2960}, pmid = {34102684}, issn = {1438-8820}, mesh = {*Cystitis, Interstitial ; Humans ; Male ; *Microbiota ; Pelvic Pain ; *Prostatitis ; }, abstract = {The use of modern molecular technologies in the last decade has given us new insights into the complex interactions of the human microbiome in health and in the pathogenesis of diseases. Among other things, the sterility concept of the urinary tract has been discarded and the goal is now to identify the different microbial signatures associated with various diseases. Dysbalances of the microbiome are increasingly suspected of causing negative effects on various malignant and benign diseases. Recently, such associations have also been shown for prostate carcinoma, renal cell carcinoma and urinary bladder carcinoma. This may lead to the discovery of new potential biomarkers for the diagnosis and as a therapeutic target of the diseases mentioned. For the diagnosis of some benign diseases such as interstitial cystitis, urge incontinence and chronic prostatitis or chronic pelvic pain syndrome, microbial involvement was previously considered an exclusion criterion. However, current studies show that the individual patient's microbiome can have an influence on the development and severity of the respective disease.}, }
@article {pmid34098872, year = {2021}, author = {Weissman, JL and Dogra, S and Javadi, K and Bolten, S and Flint, R and Davati, C and Beattie, J and Dixit, K and Peesay, T and Awan, S and Thielen, P and Breitwieser, F and Johnson, PLF and Karig, D and Fagan, WF and Bewick, S}, title = {Exploring the functional composition of the human microbiome using a hand-curated microbial trait database.}, journal = {BMC bioinformatics}, volume = {22}, number = {1}, pages = {306}, pmid = {34098872}, issn = {1471-2105}, support = {#W911NF-14-1-0490//Army Research Laboratory/ ; }, mesh = {*Bacteria/genetics ; Humans ; *Microbiota ; Phenotype ; }, abstract = {BACKGROUND: Even when microbial communities vary wildly in their taxonomic composition, their functional composition is often surprisingly stable. This suggests that a functional perspective could provide much deeper insight into the principles governing microbiome assembly. Much work to date analyzing the functional composition of microbial communities, however, relies heavily on inference from genomic features. Unfortunately, output from these methods can be hard to interpret and often suffers from relatively high error rates.<br><br>RESULTS: We built and analyzed a domain-specific microbial trait database from known microbe-trait pairs recorded in the literature to better understand the functional composition of the human microbiome. Using a combination of phylogentically conscious machine learning tools and a network science approach, we were able to link particular traits to areas of the human body, discover traits that determine the range of body areas a microbe can inhabit, and uncover drivers of metabolic breadth.<br><br>CONCLUSIONS: Domain-specific trait databases are an effective compromise between noisy methods to infer complex traits from genomic data and exhaustive, expensive attempts at database curation from the literature that do not focus on any one subset of taxa. They provide an accurate account of microbial traits and, by limiting the number of taxa considered, are feasible to build within a reasonable time-frame. We present a database specific for the human microbiome, in the hopes that this will prove useful for research into the functional composition of human-associated microbial communities.}, }
@article {pmid34093887, year = {2021}, author = {Zhang, H and Chen, J and Li, Z and Liu, L}, title = {Testing for mediation effect with application to human microbiome data.}, journal = {Statistics in biosciences}, volume = {13}, number = {2}, pages = {313-328}, pmid = {34093887}, issn = {1867-1764}, support = {R01 GM123014/GM/NIGMS NIH HHS/United States ; R21 AG063370/AG/NIA NIH HHS/United States ; UL1 TR002345/TR/NCATS NIH HHS/United States ; }, abstract = {Mediation analysis has been commonly used to study the effect of an exposure on an outcome through a mediator. In this paper, we are interested in exploring the mediation mechanism of microbiome, whose special features make the analysis challenging. We consider the isometric logratio transformation of the relative abundance as the mediator variable. Then, we present a de-biased Lasso estimate for the mediator of interest and derive its standard error estimator, which can be used to develop a test procedure for the interested mediation effect. Extensive simulation studies are conducted to assess the performance of our method. We apply the proposed approach to test the mediation effect of human gut microbiome between the dietary fiber intake and body mass index.}, }
@article {pmid34089008, year = {2021}, author = {Visick, KL and Stabb, EV and Ruby, EG}, title = {A lasting symbiosis: how Vibrio fischeri finds a squid partner and persists within its natural host.}, journal = {Nature reviews. Microbiology}, volume = {19}, number = {10}, pages = {654-665}, pmid = {34089008}, issn = {1740-1534}, support = {R01 GM135254/GM/NIGMS NIH HHS/United States ; R01 OD011024/OD/NIH HHS/United States ; R35 GM130355/GM/NIGMS NIH HHS/United States ; R37 AI050661/AI/NIAID NIH HHS/United States ; }, mesh = {Aliivibrio fischeri/*physiology ; Animals ; Decapodiformes/anatomy &amp; histology/*microbiology ; Evolution, Molecular ; Hawaii ; *Host Microbial Interactions ; Seawater/microbiology ; *Symbiosis ; }, abstract = {As our understanding of the human microbiome progresses, so does the need for natural experimental animal models that promote a mechanistic understanding of beneficial microorganism-host interactions. Years of research into the exclusive symbiosis between the Hawaiian bobtail squid, Euprymna scolopes, and the bioluminescent bacterium Vibrio fischeri have permitted a detailed understanding of those bacterial genes underlying signal exchange and rhythmic activities that result in a persistent, beneficial association, as well as glimpses into the evolution of symbiotic competence. Migrating from the ambient seawater to regions deep inside the light-emitting organ of the squid, V. fischeri experiences, recognizes and adjusts to the changing environmental conditions. Here, we review key advances over the past 15 years that are deepening our understanding of these events.}, }
@article {pmid34084131, year = {2021}, author = {Hollingsworth, BA and Cassatt, DR and DiCarlo, AL and Rios, CI and Satyamitra, MM and Winters, TA and Taliaferro, LP}, title = {Acute Radiation Syndrome and the Microbiome: Impact and Review.}, journal = {Frontiers in pharmacology}, volume = {12}, number = {}, pages = {643283}, pmid = {34084131}, issn = {1663-9812}, abstract = {Study of the human microbiota has been a centuries-long endeavor, but since the inception of the National Institutes of Health (NIH) Human Microbiome Project in 2007, research has greatly expanded, including the space involving radiation injury. As acute radiation syndrome (ARS) is multisystemic, the microbiome niches across all areas of the body may be affected. This review highlights advances in radiation research examining the effect of irradiation on the microbiome and its potential use as a target for medical countermeasures or biodosimetry approaches, or as a medical countermeasure itself. The authors also address animal model considerations for designing studies, and the potential to use the microbiome as a biomarker to assess radiation exposure and predict outcome. Recent research has shown that the microbiome holds enormous potential for mitigation of radiation injury, in the context of both radiotherapy and radiological/nuclear public health emergencies. Gaps still exist, but the field is moving forward with much promise.}, }
@article {pmid34080897, year = {2021}, author = {Patpatia, S and Yilmaz, O and Ylänne, M and Kiljunen, S}, title = {Isolation and Genomic Analysis of the Phage vB_PaeP_fHoPae04 Infecting Pseudomonas aeruginosa.}, journal = {Microbiology resource announcements}, volume = {10}, number = {22}, pages = {e0007621}, pmid = {34080897}, issn = {2576-098X}, support = {//Jane ja Aatos Erkon S&#xe4;&#xe4;ti&#xf6; (J&amp;AE)/ ; //Special state subsidy for health science research/ ; //Opetushallitus (EDUFI)/ ; }, abstract = {Here, we report the genomic sequence of Pseudomonas aeruginosa phage vB_PaeP_fHoPae04, isolated from hospital wastewater in Helsinki, Finland. The phage genome is 45,491 bp long, has a G+C content of 52.2%, and contains 70 protein-coding genes and 3 tRNA genes.}, }
@article {pmid34077717, year = {2021}, author = {Hanssen, NMJ and de Vos, WM and Nieuwdorp, M}, title = {Fecal microbiota transplantation in human metabolic diseases: From a murky past to a bright future?.}, journal = {Cell metabolism}, volume = {33}, number = {6}, pages = {1098-1110}, doi = {10.1016/j.cmet.2021.05.005}, pmid = {34077717}, issn = {1932-7420}, mesh = {Clostridium Infections/*therapy ; Colitis, Ulcerative/*therapy ; Diabetes Mellitus, Type 1/*therapy ; Fecal Microbiota Transplantation/*methods ; Humans ; }, abstract = {Fecal microbiota transplantation (FMT) is gaining considerable traction as a therapeutic approach to influence the course of a plethora of chronic conditions, ranging from metabolic syndrome and malignancies to auto-immune and neurological diseases, and helped to establish the contribution of the gut microbiome to these conditions. Although FMT procedures have yielded important mechanistic insights, their use in clinical practice may be limited due to practical objections in the setting of metabolic diseases. While its applicability is established to treat recurrent Clostridiodes difficile, FMT is emerging in ulcerative colitis and various other diseases. A particularly new insight is that FMTs may not only alter insulin sensitivity but may also alter the course of type 1 diabetes by attenuating underlying auto-immunity. In this review, we will outline the major principles and pitfalls of FMT and where optimization of study design and the procedure itself will further advance the field of cardiometabolic medicine.}, }
@article {pmid34076695, year = {2021}, author = {Sanders, DJ and Inniss, S and Sebepos-Rogers, G and Rahman, FZ and Smith, AM}, title = {The role of the microbiome in gastrointestinal inflammation.}, journal = {Bioscience reports}, volume = {41}, number = {6}, pages = {}, pmid = {34076695}, issn = {1573-4935}, mesh = {Animals ; Autoimmune Diseases/immunology/metabolism/microbiology/therapy ; Bacteria/immunology/*metabolism ; Celiac Disease/immunology/metabolism/microbiology/therapy ; Dysbiosis ; Fecal Microbiota Transplantation ; Gastrointestinal Diseases/immunology/metabolism/*microbiology/therapy ; *Gastrointestinal Microbiome ; Humans ; Immunity, Mucosal ; Inflammation Mediators/metabolism ; Inflammatory Bowel Diseases/immunology/metabolism/microbiology/therapy ; Intestines/immunology/metabolism/*microbiology ; Metabolic Syndrome/immunology/metabolism/microbiology/therapy ; Pathogen-Associated Molecular Pattern Molecules/metabolism ; Probiotics/therapeutic use ; Signal Transduction ; }, abstract = {The microbiome plays an important role in maintaining human health. Despite multiple factors being attributed to the shaping of the human microbiome, extrinsic factors such diet and use of medications including antibiotics appear to dominate. Mucosal surfaces, particularly in the gut, are highly adapted to be able to tolerate a large population of microorganisms whilst still being able to produce a rapid and effective immune response against infection. The intestinal microbiome is not functionally independent from the host mucosa and can, through presentation of microbe-associated molecular patterns (MAMPs) and generation of microbe-derived metabolites, fundamentally influence mucosal barrier integrity and modulate host immunity. In a healthy gut there is an abundance of beneficial bacteria that help to preserve intestinal homoeostasis, promote protective immune responses, and limit excessive inflammation. The importance of the microbiome is further highlighted during dysbiosis where a loss of this finely balanced microbial population can lead to mucosal barrier dysfunction, aberrant immune responses, and chronic inflammation that increases the risk of disease development. Improvements in our understanding of the microbiome are providing opportunities to harness members of a healthy microbiota to help reverse dysbiosis, reduce inflammation, and ultimately prevent disease progression.}, }
@article {pmid34074026, year = {2021}, author = {Murovec, B and Deutsch, L and Stres, B}, title = {General Unified Microbiome Profiling Pipeline (GUMPP) for Large Scale, Streamlined and Reproducible Analysis of Bacterial 16S rRNA Data to Predicted Microbial Metagenomes, Enzymatic Reactions and Metabolic Pathways.}, journal = {Metabolites}, volume = {11}, number = {6}, pages = {}, pmid = {34074026}, issn = {2218-1989}, support = {P2-0095//Javna Agencija za Raziskovalno Dejavnost RS/ ; SRA MR+ #51867//Javna Agencija za Raziskovalno Dejavnost RS/ ; Guest Professorship to BS//Universit&#xe4;t Innsbruck/ ; }, abstract = {General Unified Microbiome Profiling Pipeline (GUMPP) was developed for large scale, streamlined and reproducible analysis of bacterial 16S rRNA data and prediction of microbial metagenomes, enzymatic reactions and metabolic pathways from amplicon data. GUMPP workflow introduces reproducible data analyses at each of the three levels of resolution (genus; operational taxonomic units (OTUs); amplicon sequence variants (ASVs)). The ability to support reproducible analyses enables production of datasets that ultimately identify the biochemical pathways characteristic of disease pathology. These datasets coupled to biostatistics and mathematical approaches of machine learning can play a significant role in extraction of truly significant and meaningful information from a wide set of 16S rRNA datasets. The adoption of GUMPP in the gut-microbiota related research enables focusing on the generation of novel biomarkers that can lead to the development of mechanistic hypotheses applicable to the development of novel therapies in personalized medicine.}, }
@article {pmid34073577, year = {2021}, author = {Virtanen, J and Uusitalo, R and Korhonen, EM and Aaltonen, K and Smura, T and Kuivanen, S and Pakkanen, SH and Mero, S and Patjas, A and Riekkinen, M and Kantele, A and Nurmi, V and Hedman, K and Hepojoki, J and Sironen, T and Huhtamo, E and Vapalahti, O}, title = {Kinetics of Neutralizing Antibodies of COVID-19 Patients Tested Using Clinical D614G, B.1.1.7, and B 1.351 Isolates in Microneutralization Assays.}, journal = {Viruses}, volume = {13}, number = {6}, pages = {}, pmid = {34073577}, issn = {1999-4915}, support = {VEO 874735//Horizon 2020/ ; //Jane ja Aatos Erkon S&#xe4;&#xe4;ti&#xf6;/ ; TYH2018322//Helsingin ja Uudenmaan Sairaanhoitopiiri/ ; //Academy of Finland/ ; }, mesh = {Animals ; Antibodies, Neutralizing/*immunology ; Antibodies, Viral/immunology ; COVID-19/diagnosis/*immunology/virology ; Chlorocebus aethiops ; Coronavirus Nucleocapsid Proteins/immunology ; Humans ; Immunoglobulin G/immunology ; Kinetics ; Neutralization Tests ; Phosphoproteins/immunology ; SARS-CoV-2/genetics/*immunology/isolation &amp; purification ; Severity of Illness Index ; Spike Glycoprotein, Coronavirus/immunology ; Vero Cells ; }, abstract = {Increasing evidence suggests that some newly emerged SARS-CoV-2 variants of concern (VoCs) resist neutralization by antibodies elicited by the early-pandemic wild-type virus. We applied neutralization tests to paired recoveree sera (n = 38) using clinical isolates representing the first wave (D614G), VoC1, and VoC2 lineages (B.1.1.7 and B 1.351). Neutralizing antibodies inhibited contemporary and VoC1 lineages, whereas inhibition of VoC2 was reduced 8-fold, with 50% of sera failing to show neutralization. These results provide evidence for the increased potential of VoC2 to reinfect previously SARS-CoV-infected individuals. The kinetics of NAbs in different patients showed similar decline against all variants, with generally low initial anti-B.1.351 responses becoming undetectable, but with anti-B.1.1.7 NAbs remaining detectable (>20) for months after acute infection.}, }
@article {pmid34073356, year = {2021}, author = {Onali, T and Kivimäki, A and Mauramo, M and Salo, T and Korpela, R}, title = {Anticancer Effects of Lingonberry and Bilberry on Digestive Tract Cancers.}, journal = {Antioxidants (Basel, Switzerland)}, volume = {10}, number = {6}, pages = {}, pmid = {34073356}, issn = {2076-3921}, support = {NA//Sy&#xf6;p&#xe4;s&#xe4;&#xe4;ti&#xf6;/ ; NA//Sigrid Jus&#xe9;liuksen S&#xe4;&#xe4;ti&#xf6;/ ; NA//Helsinki University Central Hospital Research Funds/ ; NA//Jane ja Aatos Erkon S&#xe4;&#xe4;ti&#xf6;/ ; }, abstract = {Wild berries are part of traditional Nordic diets and are a rich source of phytochemicals, such as polyphenols. Various berry treatments have shown to interfere with cancer progression in vitro and in vivo. Here, we systematically reviewed the anticancer effects of two Nordic wild berries of the Vaccinium genus, lingonberry (Vaccinium vitis-idaea) and bilberry (Vaccinium myrtillus), on digestive tract cancers. The review was conducted according to the PRISMA 2020 guidelines. Searches included four databases: PubMed, Scopus, Web of Science, and CAB abstracts. Publications not written in English, case-reports, reviews, and conference abstracts were excluded. Moreover, studies with only indirect markers of cancer risk or studies with single compounds not derived from lingonberry or bilberry were not included. Meta-analysis was not performed. The majority (21/26) of studies investigated bilberry and colorectal cancer. Experimental studies on colorectal cancer indicated that bilberry inhibited intestinal tumor formation and cancer cell growth. One uncontrolled pilot human study supported the inhibitory potential of bilberry on colorectal cancer cell proliferation. Data from all 10 lingonberry studies suggests potent inhibition of cancer cell growth and tumor formation. In conclusion, in vitro and animal models support the antiproliferative and antitumor effects of various bilberry and lingonberry preparations on digestive tract cancers.}, }
@article {pmid34068736, year = {2021}, author = {Nagy, KK and Skurnik, M and Vértessy, BG}, title = {Viruses with U-DNA: New Avenues for Biotechnology.}, journal = {Viruses}, volume = {13}, number = {5}, pages = {}, pmid = {34068736}, issn = {1999-4915}, mesh = {Bacteriophages/drug effects/genetics/metabolism ; Biotechnology ; DNA, Viral/*chemistry/*genetics/metabolism ; Drug Development ; Humans ; Models, Molecular ; Nucleic Acids/chemistry/metabolism ; Protein Conformation ; Structure-Activity Relationship ; *Uracil/chemistry ; Uracil-DNA Glycosidase/chemistry/metabolism ; Viruses/drug effects/*genetics/metabolism ; }, abstract = {Deoxyuridine in DNA has recently been in the focus of research due to its intriguing roles in several physiological and pathophysiological situations. Although not an orthodox DNA base, uracil may appear in DNA via either cytosine deamination or thymine-replacing incorporations. Since these alterations may induce mutation or may perturb DNA-protein interactions, free living organisms from bacteria to human contain several pathways to counteract uracilation. These efficient and highly specific repair routes uracil-directed excision repair initiated by representative of uracil-DNA glycosylase families. Interestingly, some bacteriophages exist with thymine-lacking uracil-DNA genome. A detailed understanding of the strategy by which such phages can replicate in bacteria where an efficient repair pathway functions for uracil-excision from DNA is expected to reveal novel inhibitors that can also be used for biotechnological applications. Here, we also review the several potential biotechnological applications already implemented based on inhibitors of uracil-excision repair, such as Crispr-base-editing and detection of nascent uracil distribution pattern in complex genomes.}, }
@article {pmid34062913, year = {2021}, author = {Ndika, J and Karisola, P and Kinaret, P and Ilves, M and Alenius, H}, title = {Profiling Non-Coding RNA Changes Associated with 16 Different Engineered Nanomaterials in a Mouse Airway Exposure Model.}, journal = {Cells}, volume = {10}, number = {5}, pages = {}, pmid = {34062913}, issn = {2073-4409}, support = {309329//Seventh Framework Programme/ ; }, mesh = {Amides ; Animals ; Cluster Analysis ; Copper ; DNA Damage ; Epigenesis, Genetic ; *Gene Expression Profiling ; Gene Expression Regulation ; Lung/*drug effects/*metabolism ; Materials Testing ; Mice ; Nanoparticles ; *Nanostructures ; Nanotubes, Carbon ; Oligonucleotide Array Sequence Analysis ; Polyethylene Glycols ; *RNA, Long Noncoding ; *RNA, Untranslated ; Surface Properties ; Titanium/chemistry ; Transcriptome ; }, abstract = {Perturbations in cellular molecular events and their associated biological processes provide opportunities for hazard assessment based on toxicogenomic profiling. Long non-coding RNAs (lncRNAs) are transcribed from DNA but are typically not translated into full-length proteins. Via epigenetic regulation, they play important roles in organismal response to environmental stress. The effects of nanoparticles on this important part of the epigenome are understudied. In this study, we investigated changes in lncRNA associated with hazardous inhalatory exposure of mice to 16 engineered nanomaterials (ENM)-4 ENM (copper oxide, multi-walled carbon nanotubes, spherical titanium dioxide, and rod-like titanium dioxide particles) with 4 different surface chemistries (pristine, COOH, NH2, and PEG). Mice were exposed to 10 µg of ENM by oropharyngeal aspiration for 4 consecutive days, followed by cytological analyses and transcriptomic characterization of whole lung tissues. The number of significantly altered non-coding RNA transcripts, suggestive of their degrees of toxicity, was different for each ENM type. Particle surface chemistry and shape also had varying effects on lncRNA expression. NH2 and PEG caused the strongest and weakest responses, respectively. Via correlational analyses to mRNA expression from the same samples, we could deduce that significantly altered lncRNAs are potential regulators of genes involved in mitotic cell division and DNA damage response. This study sheds more light on epigenetic mechanisms of ENM toxicity and also emphasizes the importance of the lncRNA superfamily as toxicogenomic markers of adverse ENM exposure.}, }
@article {pmid34061886, year = {2021}, author = {Maras, B and Maggiore, A and Mignogna, G and D'Erme, M and Angiolella, L}, title = {Hyperexpression of CDRs and HWP1 genes negatively impacts on Candida albicans virulence.}, journal = {PloS one}, volume = {16}, number = {6}, pages = {e0252555}, pmid = {34061886}, issn = {1932-6203}, mesh = {Animals ; Antifungal Agents/pharmacology ; Candida albicans/drug effects/*genetics/isolation &amp; purification/*pathogenicity ; Candidiasis/microbiology ; Drug Resistance, Fungal/drug effects/genetics ; Female ; Fluconazole/pharmacology ; Fungal Proteins/*genetics ; *Gene Expression ; *Gene Expression Regulation, Fungal ; Humans ; Hyphae/genetics ; Larva/microbiology ; Lepidoptera/microbiology ; Membrane Glycoproteins/*genetics ; Membrane Transport Proteins/*genetics ; Micafungin/pharmacology ; Microbial Sensitivity Tests ; Phenotype ; Virulence/genetics ; }, abstract = {C. albicans is a commensal organism present in the human microbiome of more than 60% of the healthy population. Transition from commensalism to invasive candidiasis may occur after a local or a general failure of host's immune system. This transition to a more virulent phenotype may reside either on the capacity to form hyphae or on an acquired resistance to antifungal drugs. Indeed, overexpression of genes coding drug efflux pumps or adhesins, cell wall proteins facilitating the contact between the fungus and the host, usually marks the virulence profile of invasive Candida spp. In this paper, we compare virulence of two clinical isolates of C. albicans with that of laboratory-induced resistant strains by challenging G. mellonella larvae with these pathogens along with monitoring transcriptional profiles of drug efflux pumps genes CDR1, CDR2, MDR1 and the adhesin genes ALS1 and HWP1. Although both clinical isolates were found resistant to both fluconazole and micafungin they were found less virulent than laboratory-induced resistant strains. An unexpected behavior emerged for the former clinical isolate in which three genes, CDR1, CDR2 and HWP1, usually correlated with virulence, although hyperexpressed, conferred a less aggressive phenotype. On the contrary, in the other isolate, we observed a decreased expression of CDR1, CDR2 and HWP1as well as of MDR1 and ALS1 that may be consistent with the less aggressive performance observed in this strain. These altered gene expressions might directly influence Candida virulence or they might be an epiphenomenon of a vaster rearrangement occurred in these strains during the challenge with the host's environment. An in-deepth comprehension of this scenario could be crucial for developing interventions able to counteract C. albicans invasiveness and lethality.}, }
@article {pmid34060913, year = {2021}, author = {Zhou, J and Yu, X and Liu, J and Qin, W and He, Z and Stahl, D and Jiao, N and Zhou, J and Tu, Q}, title = {VB12Path for Accurate Metagenomic Profiling of Microbially Driven Cobalamin Synthesis Pathways.}, journal = {mSystems}, volume = {6}, number = {3}, pages = {e0049721}, pmid = {34060913}, issn = {2379-5077}, support = {31971446//National Natural Science Foundation of China (NSFC)/ ; }, abstract = {Cobalamin (vitamin B12; VB12) is an indispensable nutrient for all living entities in the Earth's biosphere and plays a vital role in both natural and host environments. Currently in the metagenomic era, gene families of interest are extracted and analyzed based on functional profiles by searching shotgun metagenomes against public databases. However, critical issues exist in applying public databases for specific processes such as VB12 biosynthesis pathways. We developed a curated functional gene database termed VB12Path for accurate metagenomic profiling of VB12 biosynthesis gene families of microbial communities in complex environments. VB12Path contains a total of 60 VB12 synthesis gene families, 287,731 sequences, and 21,154 homology groups, and it aims to provide accurate functional and taxonomic profiles of VB12 synthesis pathways for shotgun metagenomes and minimize false-positive assignments. VB12Path was applied to characterize cobalamin biosynthesis gene families in human intestines and marine environments. The results demonstrated that ocean and human intestine had dramatically different VB12 synthesis processes and that gene families belonging to salvage and remodeling pathway dominated human intestine but were lowest in the ocean ecosystem. VB12Path is expected to be a useful tool to study cobalamin biosynthesis processes via shotgun metagenome sequencing in both environmental and human microbiome research. IMPORTANCE Vitamin B12 (VB12) is an indispensable nutrient for all living entities in the world but can only be synthesized by a small subset of prokaryotes. Therefore, this small subset of prokaryotes controls ecosystem stability and host health to some extent. However, critical accuracy and comprehensiveness issues exist in applying public databases to profile VB12 synthetic gene families and taxonomic groups in complex metagenomes. In this study, we developed a curated functional gene database termed VB12Path for accurate metagenomic profiling of VB12 communities in complex environments. VB12Path is expected to serve as a valuable tool to uncover the hidden microbial communities producing this precious nutrient on Earth.}, }
@article {pmid36398283, year = {2021}, author = {Jeganathan, P and Holmes, SP}, title = {A Statistical Perspective on the Challenges in Molecular Microbial Biology.}, journal = {Journal of agricultural, biological, and environmental statistics}, volume = {26}, number = {2}, pages = {131-160}, pmid = {36398283}, issn = {1085-7117}, support = {R01 AI112401/AI/NIAID NIH HHS/United States ; }, abstract = {High throughput sequencing (HTS)-based technology enables identifying and quantifying non-culturable microbial organisms in all environments. Microbial sequences have enhanced our understanding of the human microbiome, the soil and plant environment, and the marine environment. All molecular microbial data pose statistical challenges due to contamination sequences from reagents, batch effects, unequal sampling, and undetected taxa. Technical biases and heteroscedasticity have the strongest effects, but different strains across subjects and environments also make direct differential abundance testing unwieldy. We provide an introduction to a few statistical tools that can overcome some of these difficulties and demonstrate those tools on an example. We show how standard statistical methods, such as simple hierarchical mixture and topic models, can facilitate inferences on latent microbial communities. We also review some nonparametric Bayesian approaches that combine visualization and uncertainty quantification. The intersection of molecular microbial biology and statistics is an exciting new venue. Finally, we list some of the important open problems that would benefit from more careful statistical method development.}, }
@article {pmid35936977, year = {2021}, author = {Adade, EE and Al Lakhen, K and Lemus, AA and Valm, AM}, title = {Recent progress in analyzing the spatial structure of the human microbiome: distinguishing biogeography and architecture in the oral and gut communities.}, journal = {Current opinion in endocrine and metabolic research}, volume = {18}, number = {}, pages = {275-283}, pmid = {35936977}, issn = {2451-9650}, support = {R03 DE028042/DE/NIDCR NIH HHS/United States ; }, abstract = {Fueled by technological advances in methods for sample collection and preservation in sequencing studies, and in advances in computational analyses of high content image data, the spatial structure of the human microbiome is coming to light. In this mini-review, we summarize recent developments in our understanding of the structure of two human microbiomes: the lower gut and the oral cavity. We focus on only the most recent literature and we make an important distinction between two forms of spatial structure, governed by scale: biogeography and architecture. By segmenting the study of microbiome spatial structure into two categories, we demonstrate the potential to greatly advance our understanding of the mechanistic principles that link structure and function in the microbiome.}, }
@article {pmid34056597, year = {2021}, author = {Lomsadze, A and Bonny, C and Strozzi, F and Borodovsky, M}, title = {GeneMark-HM: improving gene prediction in DNA sequences of human microbiome.}, journal = {NAR genomics and bioinformatics}, volume = {3}, number = {2}, pages = {lqab047}, pmid = {34056597}, issn = {2631-9268}, abstract = {Computational reconstruction of nearly complete genomes from metagenomic reads may identify thousands of new uncultured candidate bacterial species. We have shown that reconstructed prokaryotic genomes along with genomes of sequenced microbial isolates can be used to support more accurate gene prediction in novel metagenomic sequences. We have proposed an approach that used three types of gene prediction algorithms and found for all contigs in a metagenome nearly optimal models of protein-coding regions either in libraries of pre-computed models or constructed de novo. The model selection process and gene annotation were done by the new GeneMark-HM pipeline. We have created a database of the species level pan-genomes for the human microbiome. To create a library of models representing each pan-genome we used a self-training algorithm GeneMarkS-2. Genes initially predicted in each contig served as queries for a fast similarity search through the pan-genome database. The best matches led to selection of the model for gene prediction. Contigs not assigned to pan-genomes were analyzed by crude, but still accurate models designed for sequences with particular GC compositions. Tests of GeneMark-HM on simulated metagenomes demonstrated improvement in gene annotation of human metagenomic sequences in comparison with the current state-of-the-art gene prediction tools.}, }
@article {pmid34054778, year = {2021}, author = {Asija, K and Sutter, M and Kerfeld, CA}, title = {A Survey of Bacterial Microcompartment Distribution in the Human Microbiome.}, journal = {Frontiers in microbiology}, volume = {12}, number = {}, pages = {669024}, pmid = {34054778}, issn = {1664-302X}, support = {R01 AI114975/AI/NIAID NIH HHS/United States ; }, abstract = {Bacterial microcompartments (BMCs) are protein-based organelles that expand the metabolic potential of many bacteria by sequestering segments of enzymatic pathways in a selectively permeable protein shell. Sixty-eight different types/subtypes of BMCs have been bioinformatically identified based on the encapsulated enzymes and shell proteins encoded in genomic loci. BMCs are found across bacterial phyla. The organisms that contain them, rather than strictly correlating with specific lineages, tend to reflect the metabolic landscape of the environmental niches they occupy. From our recent comprehensive bioinformatic survey of BMCs found in genome sequence data, we find many in members of the human microbiome. Here we survey the distribution of BMCs in the different biotopes of the human body. Given their amenability to be horizontally transferred and bioengineered they hold promise as metabolic modules that could be used to probiotically alter microbiomes or treat dysbiosis.}, }
@article {pmid34052095, year = {2022}, author = {Iorio, A and Biazzo, M and Gardini, S and Muda, AO and Perno, CF and Dallapiccola, B and Putignani, L}, title = {Cross-correlation of virome-bacteriome-host-metabolome to study respiratory health.}, journal = {Trends in microbiology}, volume = {30}, number = {1}, pages = {34-46}, doi = {10.1016/j.tim.2021.04.011}, pmid = {34052095}, issn = {1878-4380}, mesh = {*Gastrointestinal Microbiome ; Metabolome ; *Microbiota ; Virome ; *Viruses/genetics ; }, abstract = {A comprehensive understanding of the microbiome-host relationship in respiratory diseases can be elucidated by exploring the landscape of virome-bacteriome-host metabolome data through unsupervised 'multi-omics' approaches. Here, we describe how the composition and function of airway and gut virome and bacteriome may contribute to pathogen establishment and propagation in airway districts and how the virome-bacteriome communities may react to respiratory diseases. A new systems medicine approach, including the characterization of respiratory and gut microbiome, may be crucial to demonstrate the likelihood and odds of respiratory disease pathophysiology, opening new avenues to the discovery of a chain of causation for key bacteria and viruses in disease severity.}, }
@article {pmid34050328, year = {2021}, author = {Tett, A and Pasolli, E and Masetti, G and Ercolini, D and Segata, N}, title = {Prevotella diversity, niches and interactions with the human host.}, journal = {Nature reviews. Microbiology}, volume = {19}, number = {9}, pages = {585-599}, pmid = {34050328}, issn = {1740-1534}, support = {R01 CA230551/CA/NCI NIH HHS/United States ; U01 CA230551/CA/NCI NIH HHS/United States ; }, mesh = {Autoimmune Diseases/microbiology ; Bacteroidaceae Infections/microbiology ; Genetic Variation ; Humans ; *Microbiota ; Phylogeny ; Prevotella/classification/*genetics/*physiology ; }, abstract = {The genus Prevotella includes more than 50 characterized species that occur in varied natural habitats, although most Prevotella spp. are associated with humans. In the human microbiome, Prevotella spp. are highly abundant in various body sites, where they are key players in the balance between health and disease. Host factors related to diet, lifestyle and geography are fundamental in affecting the diversity and prevalence of Prevotella species and strains in the human microbiome. These factors, along with the ecological relationship of Prevotella with other members of the microbiome, likely determine the extent of the contribution of Prevotella to human metabolism and health. Here we review the diversity, prevalence and potential connection of Prevotella spp. in the human host, highlighting how genomic methods and analysis have improved and should further help in framing their ecological role. We also provide suggestions for future research to improve understanding of the possible functions of Prevotella spp. and the effects of the Western lifestyle and diet on the host-Prevotella symbiotic relationship in the context of maintaining human health.}, }
@article {pmid34040632, year = {2021}, author = {Andreu-Sánchez, S and Chen, L and Wang, D and Augustijn, HE and Zhernakova, A and Fu, J}, title = {A Benchmark of Genetic Variant Calling Pipelines Using Metagenomic Short-Read Sequencing.}, journal = {Frontiers in genetics}, volume = {12}, number = {}, pages = {648229}, pmid = {34040632}, issn = {1664-8021}, abstract = {Microbes live in complex communities that are of major importance for environmental ecology, public health, and animal physiology and pathology. Short-read metagenomic shotgun sequencing is currently the state-of-the-art technique for exploring these communities. With the aid of metagenomics, our understanding of the microbiome is moving from composition toward functionality, even down to the genetic variant level. While the exploration of single-nucleotide variation in a genome is a standard procedure in genomics, and many sophisticated tools exist to perform this task, identification of genetic variation in metagenomes remains challenging. Major factors that hamper the widespread application of variant-calling analysis include low-depth sequencing of individual genomes (which is especially significant for the microorganisms present in low abundance), the existence of large genomic variation even within the same species, the absence of comprehensive reference genomes, and the noise introduced by next-generation sequencing errors. Some bioinformatics tools, such as metaSNV or InStrain, have been created to identify genetic variants in metagenomes, but the performance of these tools has not been systematically assessed or compared with the variant callers commonly used on single or pooled genomes. In this study, we benchmark seven bioinformatic tools for genetic variant calling in metagenomics data and assess their performance. To do so, we simulated metagenomic reads to mimic human microbial composition, sequencing errors, and genetic variability. We also simulated different conditions, including low and high depth of coverage and unique or multiple strains per species. Our analysis of the simulated data shows that probabilistic method-based tools such as HaplotypeCaller and Mutect2 from the GATK toolset show the best performance. By applying these tools to longitudinal gut microbiome data from the Human Microbiome Project, we show that the genetic similarity between longitudinal samples from the same individuals is significantly greater than the similarity between samples from different individuals. Our benchmark shows that probabilistic tools can be used to call metagenomes, and we recommend the use of GATK's tools as reliable variant callers for metagenomic samples.}, }
@article {pmid34037775, year = {2021}, author = {Langlois, L and Akhtar, N and Tam, KC and Dixon, B and Reid, G}, title = {Fishing for the right probiotic: host-microbe interactions at the interface of effective aquaculture strategies.}, journal = {FEMS microbiology reviews}, volume = {45}, number = {6}, pages = {}, doi = {10.1093/femsre/fuab030}, pmid = {34037775}, issn = {1574-6976}, support = {//Natural Sciences and Engineering Research Council of Canada/ ; }, mesh = {Animals ; *Aquaculture ; *Host Microbial Interactions ; *Probiotics ; }, abstract = {Effective aquaculture management strategies are paramount to global food security. Growing demands stimulate the intensification of production and create the need for practices that are both economically viable and environmentally sustainable. Importantly, pathogenic microbes continue to be detrimental to fish growth and survival. In terms of host health, the intestinal mucosa and its associated consortium of microbes have a critical role in modulating fitness and present an attractive opportunity to promote health at this interface. In light of this, the administration of probiotic microorganisms is being considered as a means to restore and sustain health in fish. Current evidence suggests that certain probiotic strains might be able to augment immunity, enhance growth rate and protect against infection in salmonids, the most economically important family of farmed finfish. This review affirms the relevance of host-microbe interactions in salmonids in light of emerging evidence, with an emphasis on intestinal health. In addition, the current understanding of the mode of action of probiotics in salmonid fish is discussed, along with delivery systems that can effectively carry the living microbes.}, }
@article {pmid34035924, year = {2021}, author = {Mansour, SR and Moustafa, MAA and Saad, BM and Hamed, R and Moustafa, AA}, title = {Impact of diet on human gut microbiome and disease risk.}, journal = {New microbes and new infections}, volume = {41}, number = {}, pages = {100845}, pmid = {34035924}, issn = {2052-2975}, abstract = {The gut microbiome of humans comprises a diverse group of trillions of microorganisms including symbiotic organisms, opportunistic pathogens and commensal organisms. This microbiota plays a major role in digesting food; it also helps with absorbing and synthesizing some nutrients and releases their metabolites, which may deliver a variety of growth-promoting and growth-inhibiting factors that influence human health either directly or indirectly. The balance between microbial species, especially those responsible for the fermentation of different substrates within the microbial community, which are in the majority, depends on daily diet. Therefore, an unbalanced diet may lead to the progression and development of human diseases. These include metabolic and inflammatory disorders, cancer and depression, as well as infant health and longevity. We provide an overview of the effect of diet on the human microbiome and assess the related risk of disease development.}, }
@article {pmid34034069, year = {2021}, author = {Lakshmanan, AP and Shatat, IF and Zaidan, S and Jacob, S and Bangarusamy, DK and Al-Abduljabbar, S and Al-Khalaf, F and Petroviski, G and Terranegra, A}, title = {Bifidobacterium reduction is associated with high blood pressure in children with type 1 diabetes mellitus.}, journal = {Biomedicine &amp; pharmacotherapy = Biomedecine &amp; pharmacotherapie}, volume = {140}, number = {}, pages = {111736}, doi = {10.1016/j.biopha.2021.111736}, pmid = {34034069}, issn = {1950-6007}, mesh = {*Bifidobacterium ; Child ; DNA, Bacterial/analysis ; DNA, Ribosomal/analysis ; Diabetes Mellitus, Type 1/*microbiology ; Fatty Acids, Volatile/analysis ; Feces/chemistry/microbiology ; Female ; Gastrointestinal Microbiome/genetics ; Humans ; Hypertension/*microbiology ; Male ; }, abstract = {Children with Type 1 diabetes mellitus (T1DM) have an elevated risk of abnormal blood pressure (BP) measurements and patterns. Both hypertension and T1DM are well-known risk factors for cardiovascular disease and kidney failure. The human microbiome has been linked to both diabetes and hypertension, but the relationship between the gut microbiome and BP in children with T1DM is not well-understood. In this cross-sectional study, we examined the relationship between resting office BP and gut microbiota composition, diversity, and richness in children with T1DM and healthy controls. We recruited 29 pediatric subjects and divided them into three groups: healthy controls (HC, n = 5), T1DM with normal BP (T1DM-Normo, n = 17), and T1DM with elevated BP (T1DM-HBP, n = 7). We measured the BP, dietary and clinical parameters for each subject. We collected fecal samples to perform the 16s rDNA sequencing and to measure the short-chain fatty acids (SCFAs) level. The microbiome downstream analysis included the relative abundance of microbiota, alpha and beta diversity, microbial markers using Linear Discriminant effect size analysis (LEfSe), potential gut microbial metabolic pathways using Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) and metabolic pathways validation using Statistical Inference of Associations between Microbial Communities And host phenotype (SIAMCAT) machine learning toolbox. Our study results showed that T1DM-HBP group had distinct gut microbial composition (at multiple taxonomic levels) and reduced diversity (richness and abundance) compared with T1DM-Normo and HC groups. Children with T1DM-HBP showed a significant reduction of Bifidobacterium levels (especially B. adolescentis, B. bifidum, and B. longum) compared to the T1DM-Normo group. We also observed unique gut-microbial metabolic pathways, such as elevated lipopolysaccharide synthesis and glutathione metabolism in children with T1DM-HBP compared to T1DM-Normo children. We can conclude that the reduction in the abundance of genus Bifidobacterium could play a significant role in elevating the BP in pediatric T1DM subjects. More studies are needed to corroborate our findings and further explore the potential contributing mechanisms we describe.}, }
@article {pmid34026985, year = {2021}, author = {Shafaei, A and Rees, J and Christophersen, CT and Devine, A and Broadhurst, D and Boyce, MC}, title = {Data supporting development and validation of liquid chromatography tandem mass spectrometry method for the quantitative determination of bile acids in feces.}, journal = {Data in brief}, volume = {36}, number = {}, pages = {107091}, pmid = {34026985}, issn = {2352-3409}, abstract = {Measuring bile acids in feces has an important role in disease prevention, diagnosis, treatment, and can be considered a measure of health status. Therefore, the primary aim was to develop a sensitive, robust, and high throughput liquid chromatography tandem mass spectrometry method with minimal sample preparation for quantitative determination of bile acids in human feces applicable to large cohorts. Due to the chemical diversity of bile acids, their wide concentration range in feces, and the complexity of feces itself, developing a sensitive and selective analytical method for bile acids is challenging. A simple extraction method using methanol suitable for subsequent quantification by liquid chromatography tandem mass spectrometry has been reported in, "Extraction and quantitative determination of bile acids in feces" [1]. The data highlight the importance of optimization of the extraction procedure and the stability of the bile acids in feces post-extraction and prior to analysis and after several freeze-thaw cycles.}, }
@article {pmid34026772, year = {2021}, author = {Beauruelle, C and Guilloux, CA and Lamoureux, C and Héry-Arnaud, G}, title = {The Human Microbiome, an Emerging Key-Player in the Sex Gap in Respiratory Diseases.}, journal = {Frontiers in medicine}, volume = {8}, number = {}, pages = {600879}, pmid = {34026772}, issn = {2296-858X}, abstract = {The sex gap is well-documented in respiratory diseases such as cystic fibrosis and chronic obstructive pulmonary disease. While the differences between males and females in prevalence, severity and prognosis are well-established, the pathophysiology of the sex difference has been poorly characterized to date. Over the past 10 years, metagenomics-based studies have revealed the presence of a resident microbiome in the respiratory tract and its central role in respiratory disease. The lung microbiome is associated with host immune response and health outcomes in both animal models and patient cohorts. The study of the lung microbiome is therefore an interesting new avenue to explore in order to understand the sex gap observed in respiratory diseases. Another important parameter to consider is the gut-lung axis, since the gut microbiome plays a crucial role in distant immune modulation in respiratory diseases, and an intestinal "microgenderome" has been reported: i.e., sexual dimorphism in the gut microbiome. The microgenderome provides new pathophysiological clues, as it defines the interactions between microbiome, sex hormones, immunity and disease susceptibility. As research on the microbiome is increasing in volume and scope, the objective of this review was to describe the state-of-the-art on the sex gap in respiratory medicine (acute pulmonary infection and chronic lung disease) in the light of the microbiome, including evidence of local (lung) or distant (gut) contributions to the pathophysiology of these diseases.}, }
@article {pmid34026454, year = {2021}, author = {Kinaret, PAS and Ndika, J and Ilves, M and Wolff, H and Vales, G and Norppa, H and Savolainen, K and Skoog, T and Kere, J and Moya, S and Handy, RD and Karisola, P and Fadeel, B and Greco, D and Alenius, H}, title = {Toxicogenomic Profiling of 28 Nanomaterials in Mouse Airways.}, journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)}, volume = {8}, number = {10}, pages = {2004588}, pmid = {34026454}, issn = {2198-3844}, mesh = {Animals ; Female ; Lung/*drug effects/metabolism/pathology ; Mice ; Mice, Inbred C57BL ; Models, Animal ; Nanostructures/chemistry/classification/*toxicity ; Toxicogenetics/*methods ; Transcriptome ; }, abstract = {Toxicogenomics opens novel opportunities for hazard assessment by utilizing computational methods to map molecular events and biological processes. In this study, the transcriptomic and immunopathological changes associated with airway exposure to a total of 28 engineered nanomaterials (ENM) are investigated. The ENM are selected to have different core (Ag, Au, TiO2, CuO, nanodiamond, and multiwalled carbon nanotubes) and surface chemistries (COOH, NH2, or polyethylene glycosylation (PEG)). Additionally, ENM with variations in either size (Au) or shape (TiO2) are included. Mice are exposed to 10 µg of ENM by oropharyngeal aspiration for 4 consecutive days, followed by extensive histological/cytological analyses and transcriptomic characterization of lung tissue. The results demonstrate that transcriptomic alterations are correlated with the inflammatory cell infiltrate in the lungs. Surface modification has varying effects on the airways with amination rendering the strongest inflammatory response, while PEGylation suppresses toxicity. However, toxicological responses are also dependent on ENM core chemistry. In addition to ENM-specific transcriptional changes, a subset of 50 shared differentially expressed genes is also highlighted that cluster these ENM according to their toxicity. This study provides the largest in vivo data set currently available and as such provides valuable information to be utilized in developing predictive models for ENM toxicity.}, }
@article {pmid34026361, year = {2021}, author = {Rogers, AE and Hu, YJ and Yue, Y and Wissel, EF and Petit Iii, RA and Jarrett, S and Christie, J and Read, TD}, title = {Shiftwork, functional bowel symptoms, and the microbiome.}, journal = {PeerJ}, volume = {9}, number = {}, pages = {e11406}, pmid = {34026361}, issn = {2167-8359}, support = {R01 GM116065/GM/NIGMS NIH HHS/United States ; }, abstract = {BACKGROUND: There are about 15 million Americans working full-time on evening, night, or rotating shifts. Between 48% and 81.9% of those working rotating or night shifts report abdominal pain, constipation, diarrhea and other symptoms of functional bowel disorders. The basis for this high prevalence of functional bowel disorders, including irritable bowel syndrome (IBS), among shift workers is unknown. Animal studies, however, suggest that circadian disruption, similar to that in shift workers, may contribute to the development of GI complaints among shift workers by altering the composition and normal diurnal rhythmicity of the resident intestinal microbes. Therefore, the present study was designed to determine if there were differences in (1) composition and diversity of the microbiome of night shift workers compared to day shift workers; and (2) the composition and diversity of the microbiome among shift workers experiencing functional bowel symptoms compared to shift workers who did not experience functional bowel symptoms.<br><br>METHODS: Fifty-one full time staff nurses who worked either 12-hour day or night shifts completed demographic information, and the Rome III IBS module. They also collected two samples of gut microbiota before the beginning and at the end of their last work shift on day 14, using validated field-tested methods consistent with the Human Microbiome Project. After DNA extraction, 16S rRNA sequencing and assignment to the genus level was completed, samples were then compared to determine if there were (1) differences in the diversity and profile of the microbiome by shift type; (2) if there were differences in the microbiome by time of day for collection; and (3) whether there were differences in the diversity and profile of the microbiome of nurses with IBS and those without IBS.<br><br>RESULTS: There were no differences in alpha or beta diversity of gut microbiota when specimens from day and night shift nurses were compared. There were however marginal differences in beta diversity when specimens collected at the beginning and end of the shifts were compared, with seven OTUs being differentially abundant when collected from day shift workers in the evening. There were also three OTUs to be differentially abundant in participants reporting IBS symptoms.}, }
@article {pmid34020714, year = {2021}, author = {Liu, C and Du, MX and Abuduaini, R and Yu, HY and Li, DH and Wang, YJ and Zhou, N and Jiang, MZ and Niu, PX and Han, SS and Chen, HH and Shi, WY and Wu, L and Xin, YH and Ma, J and Zhou, Y and Jiang, CY and Liu, HW and Liu, SJ}, title = {Enlightening the taxonomy darkness of human gut microbiomes with a cultured biobank.}, journal = {Microbiome}, volume = {9}, number = {1}, pages = {119}, pmid = {34020714}, issn = {2049-2618}, mesh = {Bacteria/genetics ; Biological Specimen Banks ; Darkness ; *Gastrointestinal Microbiome/genetics ; Humans ; *Microbiota/genetics ; RNA, Ribosomal, 16S/genetics ; }, abstract = {BACKGROUND: In gut microbiome studies, the cultured gut microbial resource plays essential roles, such as helping to unravel gut microbial functions and host-microbe interactions. Although several major studies have been performed to elucidate the cultured human gut microbiota, up to 70% of the Unified Human Gastrointestinal Genome species have not been cultured to date. Large-scale gut microbial isolation and identification as well as availability to the public are imperative for gut microbial studies and further characterizing human gut microbial functions.<br><br>RESULTS: In this study, we constructed a human Gut Microbial Biobank (hGMB; homepage: hgmb.nmdc.cn) through the cultivation of 10,558 isolates from 31 sample mixtures of 239 fresh fecal samples from healthy Chinese volunteers, and deposited 1170 strains representing 400 different species in culture collections of the International Depository Authority for long-term preservation and public access worldwide. Following the rules of the International Code of Nomenclature of Prokaryotes, 102 new species were characterized and denominated, while 28 new genera and 3 new families were proposed. hGMB represented over 80% of the common and dominant human gut microbial genera and species characterized from global human gut 16S rRNA gene amplicon data (n = 11,647) and cultured 24 "most-wanted" and "medium priority" taxa proposed by the Human Microbiome Project. We in total sequenced 115 genomes representing 102 novel taxa and 13 previously known species. Further in silico analysis revealed that the newly sequenced hGMB genomes represented 22 previously uncultured species in the Unified Human Gastrointestinal Genome (UHGG) and contributed 24 representatives of potentially "dark taxa" that had not been discovered by UHGG. The nonredundant gene catalogs generated from the hGMB genomes covered over 50% of the functionally known genes (KEGG orthologs) in the largest global human gut gene catalogs and approximately 10% of the "most wanted" functionally unknown proteins in the FUnkFams database.<br><br>CONCLUSIONS: A publicly accessible human Gut Microbial Biobank (hGMB) was established that contained 1170 strains and represents 400 human gut microbial species. hGMB expands the gut microbial resources and genomic repository by adding 102 novel species, 28 new genera, 3 new families, and 115 new genomes of human gut microbes. Video abstract.}, }
@article {pmid34020000, year = {2021}, author = {Palombo, G and Merone, M and Altomare, A and Gori, M and Terradura, C and Bacco, L and Del Chierico, F and Putignani, L and Cicala, M and Guarino, MPL and Piemonte, V}, title = {The impact of the intestinal microbiota and the mucosal permeability on three different antibiotic drugs.}, journal = {European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences}, volume = {164}, number = {}, pages = {105869}, doi = {10.1016/j.ejps.2021.105869}, pmid = {34020000}, issn = {1879-0720}, mesh = {Anti-Bacterial Agents ; Feces ; *Gastrointestinal Microbiome ; Humans ; Intestinal Mucosa ; Permeability ; *Pharmaceutical Preparations ; RNA, Ribosomal, 16S/genetics ; }, abstract = {BackgroundThe totality of bacteria, protozoa, viruses and fungi that lives in the human body is called microbiota. Human microbiota specifically colonizes the skin, the respiratory and urinary tract, the urogenital tract and the gastrointestinal system. This study focuses on the intestinal microbiota to explore the drug-microbiota relationship and, therefore, how the drug bioavailability changes in relation to the microbiota biodiversity to identify more personalized therapies, with the minimum risk of side effects. MethodsTo achieve this goal, we developed a new mathematical model with two compartments, the intestine and the blood, which takes into account the colonic mucosal permeability variation - measured by Ussing chamber system on human colonic mucosal biopsies - and the fecal microbiota composition, determined through microbiota 16S rRNA sequencing analysis. Both of the clinical parameters were evaluated in a group of Irritable Bowel Syndrome patients compared to a group of healthy controls. Key ResultsThe results show that plasma drug concentration increases as bacterial concentration decreases, while it decreases as intestinal length decreases too. ConclusionsThe study provides interesting data since in literature there are not yet mathematical models with these features, in which the importance of intestinal microbiota, the "forgotten organ", is considered both for the subject health state and in the nutrients and drugs metabolism.}, }
@article {pmid34019648, year = {2021}, author = {Pascal Andreu, V and Roel-Touris, J and Dodd, D and Fischbach, MA and Medema, MH}, title = {The gutSMASH web server: automated identification of primary metabolic gene clusters from the gut microbiota.}, journal = {Nucleic acids research}, volume = {49}, number = {W1}, pages = {W263-W270}, pmid = {34019648}, issn = {1362-4962}, support = {DP1 DK113598/DK/NIDDK NIH HHS/United States ; K08 DK110335/DK/NIDDK NIH HHS/United States ; P01 HL147823/HL/NHLBI NIH HHS/United States ; R01 DK101674/DK/NIDDK NIH HHS/United States ; }, mesh = {Bacteria/genetics/metabolism ; Gastrointestinal Microbiome/*genetics ; *Genome, Bacterial ; Genomics ; Internet ; *Software ; }, abstract = {Anaerobic bacteria from the human microbiome produce a wide array of molecules at high concentrations that can directly or indirectly affect the host. The production of these molecules, mostly derived from their primary metabolism, is frequently encoded in metabolic gene clusters (MGCs). However, despite the importance of microbiome-derived primary metabolites, no tool existed to predict the gene clusters responsible for their production. For this reason, we recently introduced gutSMASH. gutSMASH can predict 41 different known pathways, including MGCs involved in bioenergetics, but also putative ones that are candidates for novel pathway discovery. To make the tool more user-friendly and accessible, we here present the gutSMASH web server, hosted at https://gutsmash.bioinformatics.nl/. The user can either input the GenBank assembly accession or upload a genome file in FASTA or GenBank format. Optionally, the user can enable additional analyses to obtain further insights into the predicted MGCs. An interactive HTML output (viewable online or downloadable for offline use) provides a user-friendly way to browse functional gene annotations and sequence comparisons with reference gene clusters as well as gene clusters predicted in other genomes. Thus, this web server provides the community with a streamlined and user-friendly interface to analyze the metabolic potential of gut microbiomes.}, }
@article {pmid34016512, year = {2022}, author = {Khan Mirzaei, M and Deng, L}, title = {New technologies for developing phage-based tools to manipulate the human microbiome.}, journal = {Trends in microbiology}, volume = {30}, number = {2}, pages = {131-142}, doi = {10.1016/j.tim.2021.04.007}, pmid = {34016512}, issn = {1878-4380}, mesh = {Bacteria/genetics ; *Bacteriophages ; Dysbiosis ; *Gastrointestinal Microbiome ; Humans ; *Microbiota ; }, abstract = {Gut bacteria play an essential role in the human body by regulating multiple functions, producing essential metabolites, protecting against pathogen invasion, and much more. Conversely, changes in their community structure are linked to several gastrointestinal (GI) and non-GI conditions. Fortunately, these bacteria are amenable to external perturbations, but we need specific tools for their safe manipulation as nonspecific changes can cause unpredicted long-term consequences. Here, we mainly discuss recent advances in cultivation-independent technologies and argue their relevance to different key steps, that is, identifying the modulation targets and developing phage-based tools to precisely modulate gut bacteria and restore a sustainable microbiome in humans. We finally suggest multiple modulating strategies for different dysbiosis-associated diseases.}, }
@article {pmid34015282, year = {2021}, author = {Dixit, K and Chaudhari, D and Dhotre, D and Shouche, Y and Saroj, S}, title = {Restoration of dysbiotic human gut microbiome for homeostasis.}, journal = {Life sciences}, volume = {278}, number = {}, pages = {119622}, doi = {10.1016/j.lfs.2021.119622}, pmid = {34015282}, issn = {1879-0631}, mesh = {Animals ; Dysbiosis/microbiology/*therapy ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Homeostasis ; Humans ; Immunomodulation ; Microbiota ; Prebiotics/administration &amp; dosage ; Probiotics/therapeutic use ; }, abstract = {The human microbiome is a complex and dynamic ecosystem, and the imbalance of its microbial community structure from the normal state is termed dysbiosis. The dysbiotic gut microbiome has been proved to be related to several pathological conditions like Inflammatory Bowel Disease (IBD), Irritable Bowel Syndrome (IBS), Colorectal Cancer (CRC), etc., and several other extra-intestinal conditions like Type 1 &amp; 2 diabetes, obesity, etc. The complex gut microbial ecosystem starts to build before the birth of an individual. It is known to get affected by several factors such as birth mode, individual lifestyle, dietary practices, medications, and antibiotics. A dysbiotic microbiome can potentially hamper host homeostasis due to its role in immune modulation, metabolism, nutrient synthesis, etc. Restoration of the dysbiotic gut microbiome has emerged as a promising aid and a better therapeutic approach. Several approaches have been investigated to achieve this goal, including prebiotics and probiotics, Fecal Microbiota Transplantation (FMT), extracellular vesicles, immune modulation, microbial metabolites, dietary interventions, and phages. This review discusses the various factors that influence the human microbiome with respect to their cause-effect relationship and the effect of gut microbiome compositional changes on the brain through the gut-brain axis. We also discuss the practices used globally for gut microbiome restoration purposes, along with their effectiveness.}, }
@article {pmid34010477, year = {2022}, author = {Liu, J and Zhang, X and Chen, T and Wu, T and Lin, T and Jiang, L and Lang, S and Liu, L and Natarajan, L and Tu, JX and Kosciolek, T and Morton, J and Nguyen, TT and Schnabl, B and Knight, R and Feng, C and Zhong, Y and Tu, XM}, title = {A semiparametric model for between-subject attributes: Applications to beta-diversity of microbiome data.}, journal = {Biometrics}, volume = {78}, number = {3}, pages = {950-962}, pmid = {34010477}, issn = {1541-0420}, support = {UL1 TR001442/TR/NCATS NIH HHS/United States ; P30 DK120515/DK/NIDDK NIH HHS/United States ; R37 AA020703/AA/NIAAA NIH HHS/United States ; U01 AA026939/AA/NIAAA NIH HHS/United States ; K23 MH118435/MH/NIMH NIH HHS/United States ; R01 AA024726/AA/NIAAA NIH HHS/United States ; }, mesh = {Cross-Sectional Studies ; High-Throughput Nucleotide Sequencing/methods ; Humans ; *Microbiota/genetics ; }, abstract = {The human microbiome plays an important role in our health and identifying factors associated with microbiome composition provides insights into inherent disease mechanisms. By amplifying and sequencing the marker genes in high-throughput sequencing, with highly similar sequences binned together, we obtain operational taxonomic units (OTUs) profiles for each subject. Due to the high-dimensionality and nonnormality features of the OTUs, the measure of diversity is introduced as a summarization at the microbial community level, including the distance-based beta-diversity between individuals. Analyses of such between-subject attributes are not amenable to the predominant within-subject-based statistical paradigm, such as t-tests and linear regression. In this paper, we propose a new approach to model beta-diversity as a response within a regression setting by utilizing the functional response models (FRMs), a class of semiparametric models for between- as well as within-subject attributes. The new approach not only addresses limitations of current methods for beta-diversity with cross-sectional data, but also provides a premise for extending the approach to longitudinal and other clustered data in the future. The proposed approach is illustrated with both real and simulated data.}, }
@article {pmid34006865, year = {2021}, author = {Tierney, BT and Tan, Y and Kostic, AD and Patel, CJ}, title = {Gene-level metagenomic architectures across diseases yield high-resolution microbiome diagnostic indicators.}, journal = {Nature communications}, volume = {12}, number = {1}, pages = {2907}, pmid = {34006865}, issn = {2041-1723}, support = {P30 DK036836/DK/NIDDK NIH HHS/United States ; R01 AI127250/AI/NIAID NIH HHS/United States ; T32 DK110919/DK/NIDDK NIH HHS/United States ; }, mesh = {Bacteria/classification/genetics ; Cluster Analysis ; Colorectal Neoplasms/genetics/microbiology ; Computational Biology/*methods ; Diabetes Mellitus, Type 2/genetics/microbiology ; Firmicutes/genetics/physiology ; Gastrointestinal Microbiome/*genetics ; Humans ; Inflammatory Bowel Diseases/genetics/microbiology ; Metagenome/*genetics ; Metagenomics/*methods ; Microbiota/*genetics/physiology ; Phylogeny ; Species Specificity ; }, abstract = {We propose microbiome disease "architectures": linking >1 million microbial features (species, pathways, and genes) to 7 host phenotypes from 13 cohorts using a pipeline designed to identify associations that are robust to analytical model choice. Here, we quantify conservation and heterogeneity in microbiome-disease associations, using gene-level analysis to identify strain-specific, cross-disease, positive and negative associations. We find coronary artery disease, inflammatory bowel diseases, and liver cirrhosis to share gene-level signatures ascribed to the Streptococcus genus. Type 2 diabetes, by comparison, has a distinct metagenomic signature not linked to any one specific species or genus. We additionally find that at the species-level, the prior-reported connection between Solobacterium moorei and colorectal cancer is not consistently identified across models-however, our gene-level analysis unveils a group of robust, strain-specific gene associations. Finally, we validate our findings regarding colorectal cancer and inflammatory bowel diseases in independent cohorts and identify that features inversely associated with disease tend to be less reproducible than features enriched in disease. Overall, our work is not only a step towards gene-based, cross-disease microbiome diagnostic indicators, but it also illuminates the nuances of the genetic architecture of the human microbiome, including tension between gene- and species-level associations.}, }
@article {pmid34006335, year = {2021}, author = {Nearing, JT and Comeau, AM and Langille, MGI}, title = {Identifying biases and their potential solutions in human microbiome studies.}, journal = {Microbiome}, volume = {9}, number = {1}, pages = {113}, pmid = {34006335}, issn = {2049-2618}, support = {2016-05039//Canadian Network for Research and Innovation in Machining Technology, Natural Sciences and Engineering Research Council of Canada (CA)/ ; }, mesh = {Bias ; Humans ; *Metagenomics ; *Microbiota/genetics ; Sequence Analysis, DNA ; Specimen Handling ; }, abstract = {Advances in DNA sequencing technology have vastly improved the ability of researchers to explore the microbial inhabitants of the human body. Unfortunately, while these studies have uncovered the importance of these microbial communities to our health, they often do not result in similar findings. One possible reason for the disagreement in these results is due to the multitude of systemic biases that are introduced during sequence-based microbiome studies. These biases begin with sample collection and continue to be introduced throughout the entire experiment leading to an observed community that is significantly altered from the true underlying microbial composition. In this review, we will highlight the various steps in typical sequence-based human microbiome studies where significant bias can be introduced, and we will review the current efforts within the field that aim to reduce the impact of these biases. Video abstract.}, }
@article {pmid33998505, year = {2021}, author = {Requena, T and Velasco, M}, title = {The human microbiome in sickness and in health.}, journal = {Revista clinica espanola}, volume = {221}, number = {4}, pages = {233-240}, doi = {10.1016/j.rceng.2019.07.018}, pmid = {33998505}, issn = {2254-8874}, mesh = {*Gastrointestinal Microbiome ; Humans ; Intestines ; *Microbiota ; Phylogeny ; Symbiosis ; }, abstract = {The study of the human microbiome has led to an exceptional increase in the current understanding of the importance of microbiota for health throughout all stages of life. Human microbial colonization occurs in the skin, genitourinary system and, mainly, in the oral cavity and intestinal tract. In these locations, the human microbiota establishes a symbiotic relationship with the host and helps maintain physiological homeostasis. Lifestyle, age, diet and use of antibiotics are the main regulators of the composition and functionality of human microbiota. Recent studies have indicated the reduction in microbial diversity as one of the contributors to the development of diseases. In addition to phylogenetic diversity studies, further metagenomic studies are needed at the functional level of the human microbiome to improve our understanding of its involvement in human health.}, }
@article {pmid33998042, year = {2021}, author = {Herzig, AF and Velo-Suárez, L and Le Folgoc, G and Boland, A and Blanché, H and Olaso, R and Le Roux, L and Delmas, C and Goldberg, M and Zins, M and Lethimonnier, F and Deleuze, JF and Génin, E}, title = {Evaluation of saliva as a source of accurate whole-genome and microbiome sequencing data.}, journal = {Genetic epidemiology}, volume = {45}, number = {5}, pages = {537-548}, doi = {10.1002/gepi.22386}, pmid = {33998042}, issn = {1098-2272}, mesh = {Genome, Human ; Genotype ; Humans ; *Microbiota/genetics ; *Saliva ; Whole Genome Sequencing ; }, abstract = {This study sets out to establish the suitability of saliva-based whole-genome sequencing (WGS) through a comparison against blood-based WGS. To fully appraise the observed differences, we developed a novel technique of pseudo-replication. We also investigated the potential of characterizing individual salivary microbiomes from non-human DNA fragments found in saliva. We observed that the majority of discordant genotype calls between blood and saliva fell into known regions of the human genome that are typically sequenced with low confidence; and could be identified by quality control measures. Pseudo-replication demonstrated that the levels of discordance between blood- and saliva-derived WGS data were entirely similar to what one would expect between technical replicates if an individual's blood or saliva had been sequenced twice. Finally, we successfully sequenced salivary microbiomes in parallel to human genomes as demonstrated by a comparison against the Human Microbiome Project.}, }
@article {pmid33995921, year = {2021}, author = {Li, W and Ma, ZS}, title = {Population-level diversity-disease relationship (p-DDR) in the human microbiome associated diseases.}, journal = {Computational and structural biotechnology journal}, volume = {19}, number = {}, pages = {2297-2306}, pmid = {33995921}, issn = {2001-0370}, abstract = {Diversity-disease relationship (DDR) is a de facto standard analysis in the studies of human microbiome associated diseases (MADs). For example, the species richness or Shannon entropy are routinely compared between the healthy and diseased groups. Nevertheless, the basic scale of the standard diversity analysis is individual subject rather than a cohort or population because the diversity is computed for individual samples, not for the group. Here we aim to expand the current DDR study from individual focus to population level, which can offer important insights for understanding the epidemiology of MADs. We analyzed the diversity-disease relationship at cohort scale based on a collection of 23 datasets covering the major human MADs. Methodologically, we harness the power of a recent extension to the classic species-area relationship (SAR), i.e., the diversity-area relationship (DAR), to achieve the expansion from individual DDR to inter-subject diversity scaling analysis. Specifically, we apply the DAR analysis to estimate and compare the potentially maximal accrual diversities of the healthy and diseases groups, as well as the inter-subject diversity scaling parameters and the individual-to-population diversity ratios. It was shown that, except for the potential diversity (D max) at the cohort level in approximately 5.4% cases of MADs, DAR parameters displayed no significant differences between healthy and diseased treatments. That is, the DAR parameters are rather resilient against MADs, except for the potential diversity in some diseases. We compared our population-level DDR with the existing individual-level DDR patterns and proposed a hypothesis to interpret their differences.}, }
@article {pmid33995915, year = {2021}, author = {Brereton, NJB and Pitre, FE and Gonzalez, E}, title = {Reanalysis of the Mars500 experiment reveals common gut microbiome alterations in astronauts induced by long-duration confinement.}, journal = {Computational and structural biotechnology journal}, volume = {19}, number = {}, pages = {2223-2235}, pmid = {33995915}, issn = {2001-0370}, abstract = {Maintaining astronaut health throughout long-duration spaceflight is essential to the feasibility of a manned mission to Mars. The ground-based Mars500 experiment investigated long-duration health by isolating six astronauts for 520 days, the longest controlled human confinement study conducted to date. After 520 days, astronauts had uniform strength and lean body mass losses, and increased fasting plasma glucose, calprotectin, and neutrophil levels characteristic of intestinal inflammation but previous analyses revealed no common significant changes in gut microbiota. This study reanalysed data from early (days 7-45) and late (days 420-520) faecal samples and identified 408 exact sequence variants (ESVs), including 213 shared by all astronauts. Thirty-two ESVs were significantly differentially abundant over time, including depletion of keystone resistant starch degrading, anti-inflammatory and insulin sensitivity-associated species, such as Faecalibacterium prausnitzii, Ruminococcus bromii, Blautia luti, Anaerostipes hadrus, Roseburia faecis, and Lactobacillus rogosae, and enrichment of yet-to-be-cultured bacteria. Additionally, the extraordinary experimental confinement allowed observation of microbiota potentially shared between astronauts and their habitat. Forty-nine species were shared, representing 49% and 12% of the human and environmental microbiome diversity, respectively. These findings reveal the microbiota which significantly altered in relative abundance throughout confinement, including species known to influence inflammation and host glucose homeostasis consistent with astronaut symptoms. Identification of microbiome alterations after 520 days of isolation represents a missing piece connecting Mars500 astronaut physiological studies. Knowledge of the impact of long-term confinement upon the human microbiome helps to improve our understanding of how humans interact with their habitats and is a valuable step forward towards enabling long-duration spaceflight.}, }
@article {pmid33985676, year = {2021}, author = {Neckovic, A and van Oorschot, RAH and Szkuta, B and Durdle, A}, title = {Identifying background microbiomes in an evidence recovery laboratory: A preliminary study.}, journal = {Science &amp; justice : journal of the Forensic Science Society}, volume = {61}, number = {3}, pages = {280-290}, doi = {10.1016/j.scijus.2021.01.001}, pmid = {33985676}, issn = {1876-4452}, mesh = {Bacteria ; Humans ; *Microbiota/genetics ; Prospective Studies ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; }, abstract = {16S rRNA profiling of bacterial communities may have forensic utility in the identification or association of individuals involved with criminal activities. Microbial profiling of evidence may, in the future, be performed within environments currently utilised for human DNA recovery, such as a forensic biology laboratory. It would be important to establish the background microbiome of such an environment to determine the potential presence of human or environmental microbial signatures to assist forensic scientists in the appropriate interpretation of target microbial communities. This study sampled various surfaces of an Evidence Recovery Laboratory (ERL) on three occasions including (a) before a monthly deep-clean, (b) immediately following the deep-clean, and (c) immediately after the laboratory's use by a single participant for the purposes of routine item examinations. Microbial profiles were also generated for the involved participant and researcher for comparison purposes. Additionally, human nuclear DNA was profiled for each of the samples collected, using standard forensic profiling techniques, to provide a prospective link to the presence or absence of a background microbial signature within the ERL after its use. Taxonomic distributions across ERL samples revealed no consistent signature of any of the items sampled over time, however, major phyla noted within all ERL samples across the three timepoints were consistent with those found in human skin microbiomes. PCoA plots based on the Unweighted Unifrac metric revealed some clustering between participant microbial reference samples and surfaces of the ERL after use, suggesting that despite a lack of direct contact, and adherence to standard operating procedures (SOPs) suitable for human DNA recovery, microbiomes may be deposited into a forensic setting over time. The reference samples collected from the involved participant and researcher generated full STR profiles. Human DNA was observed to varying degrees in samples taken from the ERL across each of the sampling timepoints. There was no correlation observed between samples that contained or did not contain detectable quantities of human nuclear DNA and microbial profile outputs.}, }
@article {pmid33972424, year = {2021}, author = {Fellows Yates, JA and Velsko, IM and Aron, F and Posth, C and Hofman, CA and Austin, RM and Parker, CE and Mann, AE and Nägele, K and Arthur, KW and Arthur, JW and Bauer, CC and Crevecoeur, I and Cupillard, C and Curtis, MC and Dalén, L and Díaz-Zorita Bonilla, M and Díez Fernández-Lomana, JC and Drucker, DG and Escribano Escrivá, E and Francken, M and Gibbon, VE and González Morales, MR and Grande Mateu, A and Harvati, K and Henry, AG and Humphrey, L and Menéndez, M and Mihailović, D and Peresani, M and Rodríguez Moroder, S and Roksandic, M and Rougier, H and Sázelová, S and Stock, JT and Straus, LG and Svoboda, J and Teßmann, B and Walker, MJ and Power, RC and Lewis, CM and Sankaranarayanan, K and Guschanski, K and Wrangham, RW and Dewhirst, FE and Salazar-García, DC and Krause, J and Herbig, A and Warinner, C}, title = {The evolution and changing ecology of the African hominid oral microbiome.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {118}, number = {20}, pages = {}, pmid = {33972424}, issn = {1091-6490}, support = {R01 DE016937/DE/NIDCR NIH HHS/United States ; R01 DE024468/DE/NIDCR NIH HHS/United States ; R01 GM089886/GM/NIGMS NIH HHS/United States ; R37 DE016937/DE/NIDCR NIH HHS/United States ; }, mesh = {Africa ; Animals ; Bacteria/classification/genetics ; Biofilms ; *Biological Evolution ; Dental Plaque/microbiology ; Ecology/*methods ; Geography ; Gorilla gorilla/microbiology ; Hominidae/classification/*microbiology ; Humans ; Metagenome/*genetics ; Microbiota/*genetics ; Mouth/*microbiology ; Pan troglodytes/microbiology ; Phylogeny ; }, abstract = {The oral microbiome plays key roles in human biology, health, and disease, but little is known about the global diversity, variation, or evolution of this microbial community. To better understand the evolution and changing ecology of the human oral microbiome, we analyzed 124 dental biofilm metagenomes from humans, including Neanderthals and Late Pleistocene to present-day modern humans, chimpanzees, and gorillas, as well as New World howler monkeys for comparison. We find that a core microbiome of primarily biofilm structural taxa has been maintained throughout African hominid evolution, and these microbial groups are also shared with howler monkeys, suggesting that they have been important oral members since before the catarrhine-platyrrhine split ca. 40 Mya. However, community structure and individual microbial phylogenies do not closely reflect host relationships, and the dental biofilms of Homo and chimpanzees are distinguished by major taxonomic and functional differences. Reconstructing oral metagenomes from up to 100 thousand years ago, we show that the microbial profiles of both Neanderthals and modern humans are highly similar, sharing functional adaptations in nutrient metabolism. These include an apparent Homo-specific acquisition of salivary amylase-binding capability by oral streptococci, suggesting microbial coadaptation with host diet. We additionally find evidence of shared genetic diversity in the oral bacteria of Neanderthal and Upper Paleolithic modern humans that is not observed in later modern human populations. Differences in the oral microbiomes of African hominids provide insights into human evolution, the ancestral state of the human microbiome, and a temporal framework for understanding microbial health and disease.}, }
@article {pmid33972384, year = {2021}, author = {Rinaldi, F and Giuliani, G and Pinto, D}, title = {Importance of preserving the resident microflora of the skin to improve immunological response.}, journal = {Journal of investigative medicine : the official publication of the American Federation for Clinical Research}, volume = {69}, number = {7}, pages = {1386-1387}, pmid = {33972384}, issn = {1708-8267}, mesh = {Humans ; *Immunity, Innate ; *Skin/immunology/microbiology ; }, }
@article {pmid33968795, year = {2021}, author = {Kushugulova, A and Löber, U and Akpanova, S and Rysbekov, K and Kozhakhmetov, S and Khassenbekova, Z and Essex, M and Nurgozhina, A and Nurgaziyev, M and Babenko, D and Markó, L and Forslund, SK}, title = {Dynamic Changes in Microbiome Composition Following Mare's Milk Intake for Prevention of Collateral Antibiotic Effect.}, journal = {Frontiers in cellular and infection microbiology}, volume = {11}, number = {}, pages = {622735}, pmid = {33968795}, issn = {2235-2988}, mesh = {Animals ; Anti-Bacterial Agents ; Child ; Female ; Horses ; Humans ; *Microbiota ; *Milk ; Pilot Projects ; RNA, Ribosomal, 16S/genetics ; }, abstract = {INTRODUCTION: Probiotics and prebiotics are widely used for recovery of the human gut microbiome after antibiotic treatment. High antibiotic usage is especially common in children with developing microbiome. We hypothesized that dry Mare's milk, which is rich in biologically active substances without containing live bacteria, could be used as a prebiotic in promoting microbial diversity following antibiotic treatment in children. The present pilot study aims to determine the impacts of dry Mare's milk on the diversity of gut bacterial communities when administered during antibiotic treatment and throughout the subsequent recovery phase.<br><br>METHODS: Six children aged 4 to 5 years and diagnosed with bilateral bronchopneumonia were prescribed cephalosporin antibiotics. During the 60 days of the study, three children consumed dry Mare's milk whereas the other three did not. Fecal samples were collected daily during antibiotic therapy and every 5 days after antibiotic therapy. Total DNA was isolated and taxonomic composition of gut microbiota was analyzed by 16S rRNA amplicon sequencing. To assess the immune status of the gut, stool samples were analyzed by bead-based multiplex assays.<br><br>RESULTS: Mare's milk treatment seems to prevent the bloom of Mollicutes, while preventing the loss of Coriobacteriales. Immunological analysis of the stool reveals an effect of Mare's milk on local immune parameters under the present conditions.}, }
@article {pmid33965906, year = {2021}, author = {Fülöp, V and Demeter, J and Cseh, &#xc1;}, title = {[Significance and effects of prenatal and postnatal microbiome in the period of early individual development and options for interventional treatment].}, journal = {Orvosi hetilap}, volume = {162}, number = {19}, pages = {731-740}, doi = {10.1556/650.2021.32082}, pmid = {33965906}, issn = {1788-6120}, mesh = {*Autism Spectrum Disorder ; Female ; *Gastrointestinal Microbiome ; Humans ; Infant, Newborn ; *Microbiota ; Pregnancy ; Vitamins ; }, abstract = {Összefoglaló. A humán mikrobiom az emberi szervezetben és az emberi testfelszínen élő mikrobaközösségek összessége, amelyek többsége a gyomor-bél rendszerben él. Ezek a mikrobaközösségek számos és sokféle baktériumot tartalmaznak, gombákat, vírusokat, archeákat és protozoonokat. Ez a mikrobiális közösség, vagy mikrobiota, a gazdaszervezetben nagyrészt egymással kölcsönösségi viszonyban tenyészik, és gondoskodik a bélben a tápanyagok anyagcseréjéről, kalibrálja az anyagcsere-működést, tanítja az immunrendszert, fenntartja a közösség integritását, és véd a kórokozók ellen. A majdan megszületendő magzat a megfelelő tápanyagellátását az anyai véráramból kapja, és így az anyai szervezetben a mikrobiota indukálta baktériumkomponensek vagy metabolitok hatékonyan átvihetők a magzatba. Az anyai mikrobiális közösségek - ideértve a praenatalis bélrendszeri, hüvelyi, száj- és bőrmikrobiomot - a terhesség alatt valójában kifejezett változásokon mennek keresztül, amelyek befolyásolhatják az egészség megőrzését, és hozzájárulhatnak a közismert betegségek kialakulásához. A magzat nem steril, és immunológiai szempontból sem naiv, hanem az anya révén környezeti ingerek hatásaitól befolyásolva kölcsönhatásba lép az anyai immunrendszerrel. Számos anyai tényező - beleértve a hormonokat, a citokineket és a mikrobiomot - módosíthatja az intrauterin környezetet, ezáltal befolyásolva a magzati immunrendszer fejlődését. A fokozott stresszben élő anyák csecsemőinél nagyobb az allergia és a gyomor-bél rendszeri rendellenességek aránya. A várandós étrendje is befolyásolja a magzati mikrobiomot a méh közvetítésével. A bélflóránk, vagyis a mikrobiom, a belünkben élő mikrobák összessége és szimbiózisa, amelynek kényes egyensúlya már csecsemőkorban kialakul, és döntően meghatározza az intestinalis barrier és a bélasszociált immunrendszer működését. A probiotikumok szaporodásához szükséges prebiotikummal is befolyásolható a bélflóra. A pre- és a probiotikum kombinációja a szimbiotikum. Az anyatej a patogénekkel szemben protektív hatású, részben azáltal, hogy emeli a Bifidobacterium-számot az újszülött bélflórájában. A dysbiosis a kommenzális, egészséges bélflóra megváltozása. Ennek szerepét feltételezik funkcionális gastrointestinalis kórképekben, egyre több pszichiátriai és neurológiai kórképben is, mint az autizmus-spektrumzavar. Orv Hetil. 2021; 162(19): 731-740. Summary. The human microbiome is the totality of microbe communities living in the human body and on the human body surface, most of which live in the gastrointestinal tract. These microbe communities contain many and varied bacteria, fungi, viruses, archaea and protozoa. This microbial community or microbiota in the host is largely reciprocal and takes care of nutrient metabolism in the gut, calibrates metabolism, teaches the immune system, maintains community integrity, and protects against pathogens. The fetus to be born is adequately supplied with nutrients from the maternal bloodstream, and thus microbial-induced bacterial components or metabolites can be efficiently transferred to the fetus in the maternal body. Maternal microbial communities, including prenatal intestinal, vaginal, oral, and dermal microbiomes, actually undergo pronounced changes during pregnancy that can affect health maintenance and contribute to the development of well-known diseases. The fetus is not sterile or immunologically naïve, but interacts with the maternal immune system through the effects of environmental stimuli through the mother. Many maternal factors, including hormones, cytokines, and the microbiome, can modify the intrauterine environment, thereby affecting the development of the fetal immune system. Infants of mothers under increased stress have higher rates of allergies and gastrointestinal disorders. The diet of the gravida also affects the fetal microbiome through the uterus. Our intestinal flora, or microbiome, is the totality and symbiosis of the microbes living in them, the delicate balance of which is established in infancy and decisively determines the functioning of the intestinal barrier and the intestinal associated immune system. The prebiotic required for the proliferation of probiotics can also affect the intestinal flora. The combination of pre- and probiotic is symbiotic. Breast milk has a protective effect against pathogens, in part by raising the number of Bifidobacteria in the intestinal flora of the newborn. Dysbiosis is a change in the commensal, healthy gut flora. Its role is hypothesized in functional gastrointestinal disorders, as well as in more and more psychiatric and neurological disorders such as the autism spectrum disorder. Orv Hetil. 2021; 162(19): 731-740.}, }
@article {pmid33962608, year = {2021}, author = {MacDonald, KW and Chanyi, RM and Macklaim, JM and Cadieux, PA and Reid, G and Burton, JP}, title = {Streptococcus salivarius inhibits immune activation by periodontal disease pathogens.}, journal = {BMC oral health}, volume = {21}, number = {1}, pages = {245}, pmid = {33962608}, issn = {1472-6831}, mesh = {Aggregatibacter actinomycetemcomitans ; Fusobacterium nucleatum ; Humans ; *Periodontal Diseases ; Porphyromonas gingivalis ; *Streptococcus salivarius ; }, abstract = {BACKGROUND: Periodontal disease represents a major health concern. The administration of beneficial microbes has been increasing in popularity over efforts to manipulate the microbes using antimicrobial agents. This study determined the ability of Streptococcus salivarius to inhibit IL-6 and IL-8 production by gingival fibroblasts when activated by periodontal pathogens and their effect on the salivary microbiome.<br><br>METHODS: Primary human gingival fibroblasts were challenged with Porphyromonas gingivalis, Aggregatibacter actinomycetemcomitans and Fusobacterium nucleatum and a combination of all three. IL-6 and IL-8 cytokine release were measured. Using this same model, S. salivarius K12, M18 and different supernatant and whole-cell lysate fractions of S. salivarius K12 were administered to pathogen-induced fibroblasts. A patient study of healthy participants was also conducted to determine the effect S. salivarius K12 had on the native microbiome using 16S next generation sequence analysis.<br><br>RESULTS: All pathogens tested induced a significant IL-6 and IL-8 response. S. salivarius K12 or M18, did not exhibit an increase in inflammatory cytokines. When either of the probiotic strains were co-administered with a pathogen, there were significant reductions in both IL-6 and IL-8 release. This effect was also observed when gingival fibroblasts were pre-treated with either S. salivarius K12 or M18 and then stimulated with the oral pathogens. Chewing gum containing S. salivarius K12 did not alter the salivary microbiome and did not increase inflammatory markers in the oral cavity.<br><br>CONCLUSION: S. salivarius K12 and M18 prevented immune activation induced by periodontal disease pathogens. S. salivarius K12 did not alter the salivary microbiome or induce immune activation when administered as a chewing gum. These results warrant further study to determine if it may be an effective treatment in a model of periodontal disease.}, }
@article {pmid33959147, year = {2021}, author = {Xiao, W and Ma, ZS}, title = {Inter-Individual Diversity Scaling Analysis of the Human Virome With Classic Diversity-Area Relationship (DAR) Modeling.}, journal = {Frontiers in genetics}, volume = {12}, number = {}, pages = {627128}, pmid = {33959147}, issn = {1664-8021}, abstract = {The human virome is a critical component of the human microbiome, and it is believed to hold the richest diversity within human microbiomes. Yet, the inter-individual scaling (changes) of the human virome has not been formally investigated to the best of our knowledge. Here we fill the gap by applying diversity-area relationship (DAR) modeling (a recent extension to the classic species-area law in biodiversity and biogeography research) for analyzing four large datasets of the human virome with three DAR profiles: DAR scaling (z)-measuring the inter-individual heterogeneity in virome diversity, MAD (maximal accrual diversity: D max) and LGD ratio (ratio of local diversity to global diversity)-measuring the percentage of individual to population level diversity. Our analyses suggest: (i) The diversity scaling parameter (z) is rather resilient against the diseases as indicated by the lack of significant differences between the healthy and diseased treatments. (ii) The potential maximal accrual diversity (D max) is less resilient and may vary between the healthy and diseased groups or between different body sites. (iii) The LGD ratio of bacterial communities is much smaller than for viral communities, and relates to the comparatively greater heterogeneity between local vs. global diversity levels found for bacterial-biomes.}, }
@article {pmid33959106, year = {2021}, author = {Parks, DH and Rigato, F and Vera-Wolf, P and Krause, L and Hugenholtz, P and Tyson, GW and Wood, DLA}, title = {Evaluation of the Microba Community Profiler for Taxonomic Profiling of Metagenomic Datasets From the Human Gut Microbiome.}, journal = {Frontiers in microbiology}, volume = {12}, number = {}, pages = {643682}, pmid = {33959106}, issn = {1664-302X}, abstract = {A fundamental goal of microbial ecology is to accurately determine the species composition in a given microbial ecosystem. In the context of the human microbiome, this is important for establishing links between microbial species and disease states. Here we benchmark the Microba Community Profiler (MCP) against other metagenomic classifiers using 140 moderate to complex in silico microbial communities and a standardized reference genome database. MCP generated accurate relative abundance estimates and made substantially fewer false positive predictions than other classifiers while retaining a high recall rate. We further demonstrated that the accuracy of species classification was substantially increased using the Microba Genome Database, which is more comprehensive than reference datasets used by other classifiers and illustrates the importance of including genomes of uncultured taxa in reference databases. Consequently, MCP classifies appreciably more reads than other classifiers when using their recommended reference databases. These results establish MCP as best-in-class with the ability to produce comprehensive and accurate species profiles of human gastrointestinal samples.}, }
@article {pmid33956916, year = {2021}, author = {Walker, AC and Bhargava, R and Vaziriyan-Sani, AS and Pourciau, C and Donahue, ET and Dove, AS and Gebhardt, MJ and Ellward, GL and Romeo, T and Czyż, DM}, title = {Colonization of the Caenorhabditis elegans gut with human enteric bacterial pathogens leads to proteostasis disruption that is rescued by butyrate.}, journal = {PLoS pathogens}, volume = {17}, number = {5}, pages = {e1009510}, pmid = {33956916}, issn = {1553-7374}, support = {P40 OD010440/OD/NIH HHS/United States ; }, mesh = {Animals ; Butyrates/*pharmacology ; Caenorhabditis elegans/*drug effects/microbiology ; Caenorhabditis elegans Proteins/genetics/*metabolism ; Enterobacteriaceae/pathogenicity ; Enterobacteriaceae Infections/*complications/microbiology ; *Gastrointestinal Microbiome ; Humans ; Peptides/*chemistry/drug effects/metabolism ; Protein Folding ; *Proteostasis ; }, abstract = {Protein conformational diseases are characterized by misfolding and toxic aggregation of metastable proteins, often culminating in neurodegeneration. Enteric bacteria influence the pathogenesis of neurodegenerative diseases; however, the complexity of the human microbiome hinders our understanding of how individual microbes influence these diseases. Disruption of host protein homeostasis, or proteostasis, affects the onset and progression of these diseases. To investigate the effect of bacteria on host proteostasis, we used Caenorhabditis elegans expressing tissue-specific polyglutamine reporters that detect changes in the protein folding environment. We found that colonization of the C. elegans gut with enteric bacterial pathogens disrupted proteostasis in the intestine, muscle, neurons, and the gonad, while the presence of bacteria that conditionally synthesize butyrate, a molecule previously shown to be beneficial in neurodegenerative disease models, suppressed aggregation and the associated proteotoxicity. Co-colonization with this butyrogenic strain suppressed bacteria-induced protein aggregation, emphasizing the importance of microbial interaction and its impact on host proteostasis. Further experiments demonstrated that the beneficial effect of butyrate depended on the bacteria that colonized the gut and that this protective effect required SKN-1/Nrf2 and DAF-16/FOXO transcription factors. We also found that bacteria-derived protein aggregates contribute to the observed disruption of host proteostasis. Together, these results reveal the significance of enteric infection and gut dysbiosis on the pathogenesis of protein conformational diseases and demonstrate the potential of using butyrate-producing microbes as a preventative and treatment strategy for neurodegenerative disease.}, }
@article {pmid33952319, year = {2021}, author = {Xavier, RJ}, title = {Translating the human microbiome: a path to improving health.}, journal = {Genome medicine}, volume = {13}, number = {1}, pages = {78}, pmid = {33952319}, issn = {1756-994X}, support = {P30 DK043351/DK/NIDDK NIH HHS/United States ; }, mesh = {Diet ; Disease Susceptibility ; Energy Metabolism ; *Homeostasis ; *Host Microbial Interactions ; Humans ; Metagenome ; Metagenomics/methods ; Microbiota/*physiology ; T-Lymphocytes/immunology/metabolism ; }, }
@article {pmid33947803, year = {2021}, author = {Jiang, P and Wu, S and Luo, Q and Zhao, XM and Chen, WH}, title = {Metagenomic Analysis of Common Intestinal Diseases Reveals Relationships among Microbial Signatures and Powers Multidisease Diagnostic Models.}, journal = {mSystems}, volume = {6}, number = {3}, pages = {}, pmid = {33947803}, issn = {2379-5077}, abstract = {Common intestinal diseases such as Crohn's disease (CD), ulcerative colitis (UC), and colorectal cancer (CRC) share clinical symptoms and altered gut microbes, necessitating cross-disease comparisons and the use of multidisease models. Here, we performed meta-analyses on 13 fecal metagenome data sets of the three diseases. We identified 87 species and 65 pathway markers that were consistently changed in multiple data sets of the same diseases. According to their overall trends, we grouped the disease-enriched marker species into disease-specific and disease-common clusters and revealed their distinct phylogenetic relationships; species in the CD-specific cluster were phylogenetically related, while those in the CRC-specific cluster were more distant. Strikingly, UC-specific species were phylogenetically closer to CRC, likely because UC patients have higher risk of CRC. Consistent with their phylogenetic relationships, marker species had similar within-cluster and different between-cluster metabolic preferences. A portion of marker species and pathways correlated with an indicator of leaky gut, suggesting a link between gut dysbiosis and human-derived contents. Marker species showed more coordinated changes and tighter inner-connections in cases than the controls, suggesting that the diseased gut may represent a stressed environment and pose stronger selection on gut microbes. With the marker species and pathways, we constructed four high-performance (including multidisease) models with an area under the receiver operating characteristic curve (AUROC) of 0.87 and true-positive rates up to 90%, and explained their putative clinical applications. We identified consistent microbial alterations in common intestinal diseases, revealed metabolic capacities and the relationships among marker bacteria in distinct states, and supported the feasibility of metagenome-derived multidisease diagnosis.IMPORTANCE Gut microbes have been identified as potential markers in distinguishing patients from controls in colorectal cancer, ulcerative colitis, and Crohn's disease individually, whereas there lacks a systematic analysis to investigate the exclusive microbial shifts of these enteropathies with similar clinical symptoms. Our meta-analysis and cross-disease comparisons identified consistent microbial alterations in each enteropathy, revealed microbial ecosystems among marker bacteria in distinct states, and demonstrated the necessity and feasibility of metagenome-based multidisease classifications. To the best of our knowledge, this is the first study to construct multiclass models for these common intestinal diseases.}, }
@article {pmid33947329, year = {2021}, author = {Li, W and Sun, Y and Dai, L and Chen, H and Yi, B and Niu, J and Wang, L and Zhang, F and Luo, J and Wang, K and Guo, R and Li, L and Zou, Q and Ma, ZS and Miao, Y}, title = {Ecological and network analyses identify four microbial species with potential significance for the diagnosis/treatment of ulcerative colitis (UC).}, journal = {BMC microbiology}, volume = {21}, number = {1}, pages = {138}, pmid = {33947329}, issn = {1471-2180}, mesh = {Bacteria/classification/genetics/*isolation &amp; purification ; *Biodiversity ; China ; Colitis, Ulcerative/complications/diagnosis/*microbiology/therapy ; DNA, Bacterial/genetics ; Dysbiosis/complications ; Gastrointestinal Microbiome/*physiology ; Humans ; Intestinal Mucosa/*microbiology ; }, abstract = {BACKGROUND: Ulcerative colitis (UC) is one of the primary types of inflammatory bowel disease (IBD), the occurrence of which has been increasing worldwide. Although IBD is an intensively studied human microbiome-associated disease, research on Chinese populations remains relatively limited, particularly on the mucosal microbiome. The present study aimed to analyze the changes in the mucosal microbiome associated with UC from the perspectives of medical ecology and complex network analysis.<br><br>RESULTS: In total, 56 mucosal microbiome samples were collected from 28 Chinese UC patients and their healthy family partners, followed by amplicon sequencing. Based on sequencing data, we analyzed species diversity, shared species, and inter-species interactions at the whole community, main phyla, and core/periphery species levels. We identified four opportunistic "pathogens" (i.e., Clostridium tertium, Odoribacter splanchnicus, Ruminococcus gnavus, and Flavonifractor plautii) with potential significance for the diagnosis and treatment of UC, which were inhibited in healthy individuals, but unrestricted in the UC patients. In addition, we also discovered in this study: (i) The positive-to-negative links (P/N) ratio, which measures the balance of species interactions or inhibition effects in microbiome networks, was significantly higher in UC patients, indicating loss of inhibition against potentially opportunistic "pathogens" associated with dysbiosis. (ii) Previous studies have reported conflicting evidence regarding species diversity and composition between UC patients and healthy controls. Here, significant differences were found at the major phylum and core/periphery scales, but not at the whole community level. Thus, we argue that the paradoxical results found in existing studies are due to the scale effect.<br><br>CONCLUSIONS: Our results reveal changes in the ecology and network structure of the gut mucosal microbiome that might be associated with UC, and these changes might provide potential therapeutic mechanisms of UC. The four opportunistic pathogens that were identified in the present study deserve further investigation in future studies.}, }
@article {pmid33945611, year = {2021}, author = {Barber, CC and Zhang, W}, title = {Small molecule natural products in human nasal/oral microbiota.}, journal = {Journal of industrial microbiology &amp; biotechnology}, volume = {48}, number = {3-4}, pages = {}, pmid = {33945611}, issn = {1476-5535}, support = {DP2 AT009148/AT/NCCIH NIH HHS/United States ; }, mesh = {Animals ; Biological Products/*chemistry/*metabolism ; Humans ; *Microbiota ; Mouth/*microbiology ; Nose/*microbiology ; }, abstract = {Small molecule natural products are a chemically diverse class of biomolecules that fulfill myriad biological functions, including autoregulation, communication with microbial neighbors and the host, interference competition, nutrient acquisition, and resistance to oxidative stress. Human commensal bacteria are increasingly recognized as a potential source of new natural products, which may provide insight into the molecular ecology of many different human body sites as well as novel scaffolds for therapeutic development. Here, we review the scientific literature on natural products derived from residents of the human nasal/oral cavity, discuss their discovery, biosynthesis, and ecological roles, and identify key questions in the study of these compounds.}, }
@article {pmid33945270, year = {2021}, author = {Tripathi, P and Bruner, SD}, title = {Structural Basis for the Interactions of the Colibactin Resistance Gene Product ClbS with DNA.}, journal = {Biochemistry}, volume = {60}, number = {20}, pages = {1619-1625}, doi = {10.1021/acs.biochem.1c00201}, pmid = {33945270}, issn = {1520-4995}, support = {R01 CA215553/CA/NCI NIH HHS/United States ; }, mesh = {Alkylation ; DNA/chemistry ; DNA Damage ; DNA-Binding Proteins/*genetics/*metabolism/physiology ; Escherichia coli/genetics ; Escherichia coli Proteins/*genetics/*metabolism/physiology ; Mutagens/metabolism ; Peptides/pharmacology ; Polyketides/pharmacology ; RNA/chemistry ; }, abstract = {The natural product colibactin, along with its associated biosynthetic gene cluster, is an example system for the role microbially derived small molecules play in the human microbiome. This is particularly relevant in the human gut, where host microbiota is involved in various disorders, including colorectal cancer pathogenesis. Bacteria harboring the colibactin gene cluster induce alkylation of nucleobases in host DNA, forming interstrand cross-links both in vivo and in vitro. These lesions can lead to deleterious double-strand breaks and have been identified as the primary mechanism of colibactin-induced cytotoxicity. The gene product ClbS is one of several mechanisms utilized by the producing bacteria to maintain genome integrity. ClbS catalyzes hydrolytic inactivation of colibactin and has been shown to bind DNA, incurring self-resistance. Presented is the molecular basis for ClbS bound to a DNA oligonucleotide. The structure shows the interaction of the protein with the ends of a DNA duplex with terminal nucleotides flipped to the enzyme active site. The structure suggests an additional function for ClbS, the binding to damaged DNA followed by repair. Additionally, our study provides general insight into the function of the widely distributed and largely uncharacterized DUF1706 protein family.}, }
@article {pmid33925672, year = {2021}, author = {Altomare, A and Del Chierico, F and Rocchi, G and Emerenziani, S and Nuglio, C and Putignani, L and Angeletti, S and Lo Presti, A and Ciccozzi, M and Russo, A and Cocca, S and Ribolsi, M and Muscaritoli, M and Cicala, M and Guarino, MPL}, title = {Association between Dietary Habits and Fecal Microbiota Composition in Irritable Bowel Syndrome Patients: A Pilot Study.}, journal = {Nutrients}, volume = {13}, number = {5}, pages = {}, pmid = {33925672}, issn = {2072-6643}, support = {WFR GR-2011-02350817//Ministero della Salute (Italy)/ ; Italy, 201905_genetica_putignani to LP//RC Ministry of Health (Ministero della Salute, Italy)/ ; }, mesh = {Adult ; Aged ; Cross-Sectional Studies ; Diet/*methods/statistics &amp; numerical data ; Feces/*microbiology ; Feeding Behavior/*physiology ; Female ; Gastrointestinal Microbiome/*physiology ; Humans ; Irritable Bowel Syndrome/*microbiology/physiopathology ; Male ; Middle Aged ; Pilot Projects ; }, abstract = {Intestinal dysbiosis seems to play a role in the pathophysiology of irritable bowel syndrome (IBS). The present pilot study aimed to elucidate the association between nutrient intake and Mediterranean diet (MD) adherence with IBS symptoms and gut microbiota in IBS patients. The nutrient intake of 28 IBS patients and 21 controls was assessed through a food diary, the reference intake ranges (RIs) for energy-yielding macronutrients and the MD serving score (MDSS) index. MD adherence and nutrients intake were compared to IBS symptoms and fecal microbiota, obtained by 16S rRNA targeted-metagenomics. In IBS patients MDSS index was altered compared to controls (p < 0.01). IBS patients with low-MD score reported severe abdominal pain and higher flatulence point-scales. Through Linear discriminant analysis effect size (LEfSe), Erysipelotrichaceae were detected as a microbial biomarker in IBS patients with altered RIs for macronutrients intake, compared to controls. Lactobacillaceae and Lactobacillus were associated to an altered carbohydrates intake in IBS patients, while specific taxonomic biomarkers, such as Aldercreuzia, Mogibacteriaceae, Rikenellaceae, Parabacteroides and F. prausnitzii were associated with an adequate intake of nutrient in these patients. This study supports an association between dietary patterns and gut microbial biomarkers in IBS patients. Further investigations are needed to clarify these connections.}, }
@article {pmid33925267, year = {2021}, author = {Orellana, R and Arancibia, A and Badilla, L and Acosta, J and Arancibia, G and Escar, R and Ferrada, G and Seeger, M}, title = {Ecophysiological Features Shape the Distribution of Prophages and CRISPR in Sulfate Reducing Prokaryotes.}, journal = {Microorganisms}, volume = {9}, number = {5}, pages = {}, pmid = {33925267}, issn = {2076-2607}, support = {PAI/Rex 82140028//Comisi&#xf3;n Nacional de Investigaci&#xf3;n Cient&#xed;fica y Tecnol&#xf3;gica/ ; REDI170600//Comisi&#xf3;n Nacional de Investigaci&#xf3;n Cient&#xed;fica y Tecnol&#xf3;gica/ ; ANID PAI79170091//Agencia Nacional de Investigaci&#xf3;n y Desarrollo/ ; ACT172128//Agencia Nacional de Investigaci&#xf3;n y Desarrollo (PIA Ring)/ ; }, abstract = {Sulfate reducing prokaryotes (SRP) are a phylogenetically and physiologically diverse group of microorganisms that use sulfate as an electron acceptor. SRP have long been recognized as key players of the carbon and sulfur cycles, and more recently, they have been identified to play a relevant role as part of syntrophic and symbiotic relations and the human microbiome. Despite their environmental relevance, there is a poor understanding about the prevalence of prophages and CRISPR arrays and how their distribution and dynamic affect the ecological role of SRP. We addressed this question by analyzing the results of a comprehensive survey of prophages and CRISPR in a total of 91 genomes of SRP with several genotypic, phenotypic, and physiological traits, including genome size, cell volume, minimum doubling time, cell wall, and habitat, among others. Our analysis discovered 81 prophages in 51 strains, representing the 56% of the total evaluated strains. Prophages are non-uniformly distributed across the SRP phylogeny, where prophage-rich lineages belonged to Desulfovibrionaceae and Peptococcaceae. Furthermore, our study found 160 CRISPR arrays in 71 SRP, which is more abundant and widely spread than previously expected. Although there is no correlation between presence and abundance of prophages and CRISPR arrays at the strain level, our analysis showed that there is a directly proportional relation between cellular volumes and number of prophages per cell. This result suggests that there is an additional selective pressure for strains with smaller cells to get rid of foreign DNA, such as prophages, but not CRISPR, due to less availability of cellular resources. Analysis of the prophage genes encoding viral structural proteins reported that 44% of SRP prophages are classified as Myoviridae, and comparative analysis showed high level of homology, but not synteny, among prophages belonging to the Family Desulfovibrionaceae. We further recovered viral-like particles and structures that resemble outer membrane vesicles from D. vulgaris str. Hildenborough. The results of this study improved the current understanding of dynamic interactions between prophages and CRISPR with their hosts in both cultured and hitherto-uncultured SRP strains, and how their distribution affects the microbial community dynamics in several sulfidogenic natural and engineered environments.}, }
@article {pmid33923360, year = {2021}, author = {Kasurinen, J and Spruit, CM and Wicklund, A and Pajunen, MI and Skurnik, M}, title = {Screening of Bacteriophage Encoded Toxic Proteins with a Next Generation Sequencing-Based Assay.}, journal = {Viruses}, volume = {13}, number = {5}, pages = {}, pmid = {33923360}, issn = {1999-4915}, mesh = {Amino Acid Sequence ; Bacteriophages/*genetics/isolation &amp; purification/ultrastructure ; Computational Biology/methods ; Genome, Viral ; Genomics/methods ; High-Throughput Nucleotide Sequencing ; Host Specificity ; Humans ; Models, Molecular ; Protein Conformation ; Proteomics/methods ; Sequence Analysis, DNA ; Structure-Activity Relationship ; Toxins, Biological/chemistry/*genetics ; Viral Proteins/chemistry/*genetics ; }, abstract = {Bacteriophage vB_EcoM_fHy-Eco03 (fHy-Eco03 for short) was isolated from a sewage sample based on its ability to infect an Escherichia coli clinical blood culture isolate. Altogether, 32 genes encoding hypothetical proteins of unknown function (HPUFs) were identified from the genomic sequence of fHy-Eco03. The HPUFs were screened for toxic properties (toxHPUFs) with a novel, Next Generation Sequencing (NGS)-based approach. This approach identifies toxHPUF-encoding genes through comparison of gene-specific read coverages in DNA from pooled ligation mixtures before electroporation and pooled transformants after electroporation. The performance and reliability of the NGS screening assay was compared with a plating efficiency-based method, and both methods identified the fHy-Eco03 gene g05 product as toxic. While the outcomes of the two screenings were highly similar, the NGS screening assay outperformed the plating efficiency assay in both reliability and efficiency. The NGS screening assay can be used as a high throughput method in the search for new phage-inspired antimicrobial molecules.}, }
@article {pmid33923358, year = {2021}, author = {Rees, J and Radavelli Bagatini, S and Lo, J and Hodgson, JM and Christophersen, CT and Daly, RM and Magliano, DJ and Shaw, JE and Sim, M and Bondonno, CP and Blekkenhorst, LC and Dickson, JM and Lewis, JR and Devine, A}, title = {Association between Fruit and Vegetable Intakes and Mental Health in the Australian Diabetes Obesity and Lifestyle Cohort.}, journal = {Nutrients}, volume = {13}, number = {5}, pages = {}, pmid = {33923358}, issn = {2072-6643}, mesh = {Australia ; Cohort Studies ; Comorbidity ; Diabetes Mellitus/*epidemiology ; Diet/adverse effects/*methods ; Female ; Follow-Up Studies ; *Fruit ; Humans ; Life Style ; Male ; Mental Disorders/*epidemiology ; Mental Health ; Middle Aged ; Obesity/*epidemiology ; *Vegetables ; }, abstract = {Increasing prevalence of mental health disorders within the Australian population is a serious public health issue. Adequate intake of fruits and vegetables (FV), dietary fibre (DF) and resistant starch (RS) is associated with better mental and physical health. Few longitudinal studies exist exploring the temporal relationship. Using a validated food frequency questionnaire, we examined baseline FV intakes of 5845 Australian adults from the AusDiab study and estimated food group-derived DF and RS using data from the literature. Perceived mental health was assessed at baseline and 5 year follow up using SF-36 mental component summary scores (MCS). We conducted baseline cross-sectional analysis and prospective analysis of baseline dietary intake with perceived mental health at 5 years. Higher baseline FV and FV-derived DF and RS intakes were associated with better 5 year MCS (p < 0.001). A higher FV intake (754 g/d vs. 251 g/d, Q4 vs. Q1) at baseline had 41% lower odds (OR = 0.59: 95% CI 0.46-0.75) of MCS below population average (<47) at 5 year follow up. Findings were similar for FV-derived DF and RS. An inverse association was observed with discretionary food-derived DF and RS. This demonstrates the association between higher intakes of FV and FV-derived DF and RS with better 5 year mental health outcomes. Further RCTs are necessary to understand mechanisms that underlie this association including elucidation of causal effects.}, }
@article {pmid33919474, year = {2021}, author = {Hedžet, S and Rupnik, M and Accetto, T}, title = {Novel Siphoviridae Bacteriophages Infecting Bacteroides uniformis Contain Diversity Generating Retroelement.}, journal = {Microorganisms}, volume = {9}, number = {5}, pages = {}, pmid = {33919474}, issn = {2076-2607}, support = {P3-0387, P4-0097, Slovenian Research Agency Young Investigators Grant//Slovenian Research Agency/ ; }, abstract = {Intestinal phages are abundant and important components of gut microbiota, yet the isolated and characterized representatives that infect abundant gut bacteria are sparse. Here we describe the isolation of human intestinal phages infecting Bacteroidesuniformis. Bacteroides is one of the most common bacterial groups in the global human gut microbiota; however, to date not many Bacteroides specific phages are known. Phages isolated in this study belong to a novel viral genus, Bacuni, within the Siphoviridae family. Their genomes encode diversity-generating retroelements (DGR), which were shown in other bacteriophages to promote phage adaptation to rapidly changing environmental conditions and to broaden their host range. Three isolated phages showed 99.83% genome identity but one of them infected a distinct B. uniformis strain. The tropism of Bacuni phages appeared to be dependent on the interplay of DGR mediated sequence variations of gene encoding putative phage fimbrial tip proteins and mutations in host genes coding for outer-membrane proteins. We found prophages with up to 85% amino acid similarity over two-thirds of the Bacuni phage genome in the B. acidifaciens and Prevotella sp. genomes. Despite the abundance of Bacteroides within the human microbiome, we found Bacuni phages only in a limited subset of published gut metagenomes.}, }
@article {pmid33918768, year = {2021}, author = {Simões, MF and Antunes, A}, title = {Microbial Pathogenicity in Space.}, journal = {Pathogens (Basel, Switzerland)}, volume = {10}, number = {4}, pages = {}, pmid = {33918768}, issn = {2076-0817}, support = {not available//Fundo para o Desenvolvimento das Ci&#xea;ncias e da Tecnologia/ ; }, abstract = {After a less dynamic period, space exploration is now booming. There has been a sharp increase in the number of current missions and also of those being planned for the near future. Microorganisms will be an inevitable component of these missions, mostly because they hitchhike, either attached to space technology, like spaceships or spacesuits, to organic matter and even to us (human microbiome), or to other life forms we carry on our missions. Basically, we never travel alone. Therefore, we need to have a clear understanding of how dangerous our "travel buddies" can be; given that, during space missions, our access to medical assistance and medical drugs will be very limited. Do we explore space together with pathogenic microorganisms? Do our hitchhikers adapt to the space conditions, as well as we do? Do they become pathogenic during that adaptation process? The current review intends to better clarify these questions in order to facilitate future activities in space. More technological advances are needed to guarantee the success of all missions and assure the reduction of any possible health and environmental risks for the astronauts and for the locations being explored.}, }
@article {pmid33917737, year = {2021}, author = {Lee, YI and Choi, S and Roh, WS and Lee, JH and Kim, TG}, title = {Cellular Senescence and Inflammaging in the Skin Microenvironment.}, journal = {International journal of molecular sciences}, volume = {22}, number = {8}, pages = {}, pmid = {33917737}, issn = {1422-0067}, mesh = {Aging/*physiology ; Animals ; *Cellular Microenvironment ; *Cellular Senescence/genetics/radiation effects ; Fibroblasts/metabolism/radiation effects ; Humans ; Inflammation/*etiology/pathology ; Keratinocytes/drug effects/metabolism ; Melanocytes/metabolism/radiation effects ; Skin/cytology/*metabolism ; Skin Physiological Phenomena ; Skin Pigmentation ; }, abstract = {Cellular senescence and aging result in a reduced ability to manage persistent types of inflammation. Thus, the chronic low-level inflammation associated with aging phenotype is called "inflammaging". Inflammaging is not only related with age-associated chronic systemic diseases such as cardiovascular disease and diabetes, but also skin aging. As the largest organ of the body, skin is continuously exposed to external stressors such as UV radiation, air particulate matter, and human microbiome. In this review article, we present mechanisms for accumulation of senescence cells in different compartments of the skin based on cell types, and their association with skin resident immune cells to describe changes in cutaneous immunity during the aging process.}, }
@article {pmid33915854, year = {2021}, author = {Wierzbicka, A and Mańkowska-Wierzbicka, D and Mardas, M and Stelmach-Mardas, M}, title = {Role of Probiotics in Modulating Human Gut Microbiota Populations and Activities in Patients with Colorectal Cancer-A Systematic Review of Clinical Trials.}, journal = {Nutrients}, volume = {13}, number = {4}, pages = {}, pmid = {33915854}, issn = {2072-6643}, mesh = {Bacteria/classification ; Colorectal Neoplasms/*microbiology ; *Gastrointestinal Microbiome ; Humans ; *Probiotics ; }, abstract = {BACKGROUND: Growing attention has been given to the role of nutrition and alterations of microbial diversity of the gut microbiota in colorectal cancer (CRC) pathogenesis. It has been suggested that probiotics and synbiotics modulate enteric microbiota and therefore may be used as an intervention to reduce the risk of CRC. The aim of this study was to evaluate the influence of probiotics/synbiotics administration on gut microbiota in patients with CRC.<br><br>METHODS: PubMed, Scopus, and Web of Science were searched between December 2020 and January 2021. Randomized controlled trials (RCTs) recruiting adults with CRC, who have taken probiotics/synbiotics for at least 6 days were included. Changes in gut microbiota and selected biochemical and inflammatory parameters (i.e., hsCRP, IL-2, hemoglobin) were retrieved.<br><br>RESULTS: The search resulted in 198 original research articles and a final 6 were selected as being eligible, including 457 subjects. The median age of patients was 65.4 years old and they were characterized by the median BMI value: 23.8 kg/m[2]. The literature search revealed that probiotic/synbiotic administration improved enteric microbiota by increasing the abundance of beneficial bacteria such as Lactobacillus, Eubacterium, Peptostreptococcus, Bacillus and Bifidobacterium, and decreased the abundance of potentially harmful bacteria such as Fusobacterium, Porhyromonas, Pseudomonas and Enterococcus. Additionally, probiotic/synbiotic intervention improved release of antimicrobials, intestinal permeability, tight junction function in CRC patients.<br><br>CONCLUSIONS: The use of probiotics/synbiotics positively modulates enteric microbiota, improves postoperative outcomes, gut barrier function and reduces inflammatory parameters in patients suffering from CRC.}, }
@article {pmid33915727, year = {2021}, author = {Jia, B and Park, D and Chun, BH and Hahn, Y and Jeon, CO}, title = {Diet-Related Alterations of Gut Bile Salt Hydrolases Determined Using a Metagenomic Analysis of the Human Microbiome.}, journal = {International journal of molecular sciences}, volume = {22}, number = {7}, pages = {}, pmid = {33915727}, issn = {1422-0067}, support = {2017M3C1B5019250//National Research Foundation of Korea/ ; 2018R1A5A1025077//National Research Foundation of Korea/ ; }, mesh = {Amidohydrolases/chemistry/*metabolism ; Bacterial Proteins/chemistry/*metabolism ; *Diet, Ketogenic ; *Gastrointestinal Microbiome ; Humans ; Hyperphagia/*microbiology ; Metagenomics ; }, abstract = {The metabolism of bile acid by the gut microbiota is associated with host health. Bile salt hydrolases (BSHs) play a crucial role in controlling microbial bile acid metabolism. Herein, we conducted a comparative study to investigate the alterations in the abundance of BSHs using data from three human studies involving dietary interventions, which included a ketogenetic diet (KD) versus baseline diet (BD), overfeeding diet (OFD) versus underfeeding diet, and low-carbohydrate diet (LCD) versus BD. The KD increased BSH abundance compared to the BD, while the OFD and LCD did not change the total abundance of BSHs in the human gut. BSHs can be classified into seven clusters; Clusters 1 to 4 are relatively abundant in the gut. In the KD cohort, the levels of BSHs from Clusters 1, 3, and 4 increased significantly, whereas there was no notable change in the levels of BSHs from the clusters in the OFD and LCD cohorts. Taxonomic studies showed that members of the phyla Bacteroidetes, Firmicutes, and Actinobacteria predominantly produced BSHs. The KD altered the community structure of BSH-active bacteria, causing an increase in the abundance of Bacteroidetes and decrease in Actinobacteria. In contrast, the abundance of BSH-active Bacteroidetes decreased in the OFD cohort, and no significant change was observed in the LCD cohort. These results highlight that dietary patterns are associated with the abundance of BSHs and community structure of BSH-active bacteria and demonstrate the possibility of manipulating the composition of BSHs in the gut through dietary interventions to impact human health.}, }
@article {pmid33911753, year = {2020}, author = {Mann, EA and Bae, E and Kostyuchek, D and Chung, HJ and McGee, JS}, title = {The Gut Microbiome: Human Health and Inflammatory Skin Diseases.}, journal = {Annals of dermatology}, volume = {32}, number = {4}, pages = {265-272}, pmid = {33911753}, issn = {2005-3894}, abstract = {The human microbiome is a rich environment consisting of bacteria, fungi and other commensal microorganisms of the gut, mucosa and skin. The functional role of the gut microbiome includes facilitation in metabolism of macronutrients, maturation of the immune system, and production of pro- or anti-inflammatory signaling molecules and peptides. The identification of these resident organisms has brought about a new understanding of disease processes. Nevertheless, more questions remain regarding the interactions within the microbiome, its interactions with the host, and its contributions to the pathophysiology of disease. The purpose of this review is to examine the existing medical literature to highlight the role of the gut microbiome in human health, also paying attention to its role in several inflammatory skin diseases, namely atopic dermatitis, psoriasis, and rosacea.}, }
@article {pmid33910647, year = {2021}, author = {Tourlousse, DM and Narita, K and Miura, T and Sakamoto, M and Ohashi, A and Shiina, K and Matsuda, M and Miura, D and Shimamura, M and Ohyama, Y and Yamazoe, A and Uchino, Y and Kameyama, K and Arioka, S and Kataoka, J and Hisada, T and Fujii, K and Takahashi, S and Kuroiwa, M and Rokushima, M and Nishiyama, M and Tanaka, Y and Fuchikami, T and Aoki, H and Kira, S and Koyanagi, R and Naito, T and Nishiwaki, M and Kumagai, H and Konda, M and Kasahara, K and Ohkuma, M and Kawasaki, H and Sekiguchi, Y and Terauchi, J}, title = {Validation and standardization of DNA extraction and library construction methods for metagenomics-based human fecal microbiome measurements.}, journal = {Microbiome}, volume = {9}, number = {1}, pages = {95}, pmid = {33910647}, issn = {2049-2618}, mesh = {DNA ; Humans ; *Metagenomics ; *Microbiota/genetics ; Reference Standards ; Reproducibility of Results ; Sequence Analysis, DNA ; }, abstract = {BACKGROUND: Validation and standardization of methodologies for microbial community measurements by high-throughput sequencing are needed to support human microbiome research and its industrialization. This study set out to establish standards-based solutions to improve the accuracy and reproducibility of metagenomics-based microbiome profiling of human fecal samples.<br><br>RESULTS: In the first phase, we performed a head-to-head comparison of a wide range of protocols for DNA extraction and sequencing library construction using defined mock communities, to identify performant protocols and pinpoint sources of inaccuracy in quantification. In the second phase, we validated performant protocols with respect to their variability of measurement results within a single laboratory (that is, intermediate precision) as well as interlaboratory transferability and reproducibility through an industry-based collaborative study. We further ascertained the performance of our recommended protocols in the context of a community-wide interlaboratory study (that is, the MOSAIC Standards Challenge). Finally, we defined performance metrics to provide best practice guidance for improving measurement consistency across methods and laboratories.<br><br>CONCLUSIONS: The validated protocols and methodological guidance for DNA extraction and library construction provided in this study expand current best practices for metagenomic analyses of human fecal microbiota. Uptake of our protocols and guidelines will improve the accuracy and comparability of metagenomics-based studies of the human microbiome, thereby facilitating development and commercialization of human microbiome-based products. Video Abstract.}, }
@article {pmid33906915, year = {2021}, author = {Marotz, C and Cavagnero, KJ and Song, SJ and McDonald, D and Wandro, S and Humphrey, G and Bryant, M and Ackermann, G and Diaz, E and Knight, R}, title = {Evaluation of the Effect of Storage Methods on Fecal, Saliva, and Skin Microbiome Composition.}, journal = {mSystems}, volume = {6}, number = {2}, pages = {}, pmid = {33906915}, issn = {2379-5077}, support = {F31 DE028478/DE/NIDCR NIH HHS/United States ; T32 DK007202/DK/NIDDK NIH HHS/United States ; }, abstract = {As the number of human microbiome studies expand, it is increasingly important to identify cost-effective, practical preservatives that allow for room temperature sample storage. Here, we reanalyzed 16S rRNA gene amplicon sequencing data from a large sample storage study published in 2016 and performed shotgun metagenomic sequencing on remnant DNA from this experiment. Both results support the initial findings that 95% ethanol, a nontoxic, cost-effective preservative, is effective at preserving samples at room temperature for weeks. We expanded on this analysis by collecting a new set of fecal, saliva, and skin samples to determine the optimal ratio of 95% ethanol to sample. We identified optimal collection protocols for fecal samples (storing a fecal swab in 95% ethanol) and saliva samples (storing unstimulated saliva in 95% ethanol at a ratio of 1:2). Storing skin swabs in 95% ethanol reduced microbial biomass and disrupted community composition, highlighting the difficulties of low biomass sample preservation. The results from this study identify practical solutions for large-scale analyses of fecal and oral microbial communities.IMPORTANCE Expanding our knowledge of microbial communities across diverse environments includes collecting samples in places far from the laboratory. Identifying cost-effective preservatives that will enable room temperature storage of microbial communities for sequencing analysis is crucial to enabling microbiome analyses across diverse populations. Here, we validate findings that 95% ethanol efficiently preserves microbial composition at room temperature for weeks. We also identified the optimal ratio of 95% ethanol to sample for stool and saliva to preserve both microbial load and composition. These results provide rationale for an accessible, nontoxic, cost-effective solution that will enable crowdsourcing microbiome studies, such as The Microsetta Initiative, and lower the barrier for collecting diverse samples.}, }
@article {pmid33904395, year = {2021}, author = {Jost, M and Jacobson, AN and Hussmann, JA and Cirolia, G and Fischbach, MA and Weissman, JS}, title = {CRISPR-based functional genomics in human dendritic cells.}, journal = {eLife}, volume = {10}, number = {}, pages = {}, pmid = {33904395}, issn = {2050-084X}, support = {U01 CA217882/CA/NCI NIH HHS/United States ; U54 CA224081/CA/NCI NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; DP1 DK113598/DK/NIDDK NIH HHS/United States ; K99 GM130964/GM/NIGMS NIH HHS/United States ; R01 DK110174/DK/NIDDK NIH HHS/United States ; }, mesh = {Bacteroides thetaiotaomicron/immunology ; CRISPR-Associated Protein 9/*genetics/metabolism ; *CRISPR-Cas Systems ; Cells, Cultured ; *Clustered Regularly Interspaced Short Palindromic Repeats ; Cytokines/genetics/metabolism ; Dendritic Cells/drug effects/*immunology/metabolism ; *Gene Editing ; Gene Expression Regulation ; *Genomics ; Humans ; Immunity, Innate/drug effects/*genetics ; Lipopolysaccharides/pharmacology ; Phenotype ; Signal Transduction ; Toll-Like Receptor 4/agonists/genetics/metabolism ; }, abstract = {Dendritic cells (DCs) regulate processes ranging from antitumor and antiviral immunity to host-microbe communication at mucosal surfaces. It remains difficult, however, to genetically manipulate human DCs, limiting our ability to probe how DCs elicit specific immune responses. Here, we develop a CRISPR-Cas9 genome editing method for human monocyte-derived DCs (moDCs) that mediates knockouts with a median efficiency of >94% across >300 genes. Using this method, we perform genetic screens in moDCs, identifying mechanisms by which DCs tune responses to lipopolysaccharides from the human microbiome. In addition, we reveal donor-specific responses to lipopolysaccharides, underscoring the importance of assessing immune phenotypes in donor-derived cells, and identify candidate genes that control this specificity, highlighting the potential of our method to pinpoint determinants of inter-individual variation in immunity. Our work sets the stage for a systematic dissection of the immune signaling at the host-microbiome interface and for targeted engineering of DCs for neoantigen vaccination.}, }
@article {pmid33899017, year = {2021}, author = {Al, KF and Burton, JP}, title = {Processing human urine and ureteral stents for 16S rRNA amplicon sequencing.}, journal = {STAR protocols}, volume = {2}, number = {2}, pages = {100435}, pmid = {33899017}, issn = {2666-1667}, mesh = {Adult ; DNA, Bacterial/analysis/genetics ; Female ; High-Throughput Nucleotide Sequencing/*methods ; Humans ; Male ; RNA, Ribosomal, 16S/*genetics ; Sequence Analysis, DNA/*methods ; Ureter/*microbiology ; Urine/*microbiology ; }, abstract = {Ureteral stents are commonly used medical devices that harbor a unique and patient-specific microbial community. This protocol describes an optimized procedure for high-quality DNA extraction from both urine and ureteral stent samples for the purpose of downstream microbiota characterization by amplicon sequencing. Detailed instruction is provided for 16S rRNA gene V4 region sequencing with the Illumina platform, which enables accurate and reproducible microbiota profiling of low bacterial abundance urine and stent samples. For complete details on the use and execution of this protocol, please refer to Al et al. (2020).}, }
@article {pmid33898698, year = {2020}, author = {Zorba, M and Melidou, A and Patsatsi, A and Ioannou, E and Kolokotronis, A}, title = {The possible role of oral microbiome in autoimmunity.}, journal = {International journal of women's dermatology}, volume = {6}, number = {5}, pages = {357-364}, pmid = {33898698}, issn = {2352-6475}, abstract = {OBJECTIVE: The human microbiome refers to the entire habitat, including microorganisms, their genomes and the surrounding environmental conditions of the microbial ecosystem. When the equilibrium between microbial habitats and host is disturbed, dysbiosis is caused. The oral microbiome (OMB) has been implicated in the manifestation of many intra- and extraoral diseases. Lately, there has been an intense effort to investigate and specify the relationship between microbial complexes, especially that of the oral cavity and intestine and autoimmunity. This study aimed to review the current literature about the possible role of the OMB in the pathogenesis of autoimmune diseases.<br><br>METHODS: We searched for published articles in English indexed in PubMed, Medline, Research Gate and Google Scholar using a search strategy that included terms for oral microbiome, autoimmune diseases, dysbiosis and next-generation sequencing.<br><br>RESULTS: An important number of articles were gathered and used for the description of the possible impact of dysbiosis of OMB in the pathogenesis of Sj&#xf6;gren's syndrome, systemic lupus erythematosus, rheumatoid arthritis, Behcet's disease, Crohn's disease and psoriasis.<br><br>CONCLUSION: This review article draws attention to the relationship between OMB and the triggering of a number of autoimmune diseases. Although this specific topic has been previously reviewed, herein, the authors review recent literature regarding the full list of nosological entities related to the OMB, point out the interaction between the microbiome and sex hormones with regard to their role in autoimmunity and discuss novel and promising therapeutic approaches for systemic autoimmune diseases. Furthermore, the question arises of whether the OMB is associated with oral bullous autoimmune diseases.}, }
@article {pmid33897763, year = {2021}, author = {Rampelli, S and Fabbrini, M and Candela, M and Biagi, E and Brigidi, P and Turroni, S}, title = {G2S: A New Deep Learning Tool for Predicting Stool Microbiome Structure From Oral Microbiome Data.}, journal = {Frontiers in genetics}, volume = {12}, number = {}, pages = {644516}, pmid = {33897763}, issn = {1664-8021}, abstract = {Deep learning methodologies have revolutionized prediction in many fields and show the potential to do the same in microbial metagenomics. However, deep learning is still unexplored in the field of microbiology, with only a few software designed to work with microbiome data. Within the meta-community theory, we foresee new perspectives for the development and application of deep learning algorithms in the field of the human microbiome. In this context, we developed G2S, a bioinformatic tool for taxonomic prediction of the human fecal microbiome directly from the oral microbiome data of the same individual. The tool uses a deep convolutional neural network trained on paired oral and fecal samples from populations across the globe, which allows inferring the stool microbiome at the family level more accurately than other available approaches. The tool can be used in retrospective studies, where fecal sampling was not performed, and especially in the field of paleomicrobiology, as a unique opportunity to recover data related to ancient gut microbiome configurations. G2S was validated on already characterized oral and fecal sample pairs, and then applied to ancient microbiome data from dental calculi, to derive putative intestinal components in medieval subjects.}, }
@article {pmid33883174, year = {2021}, author = {de Clercq, NC and van den Ende, T and Prodan, A and Hemke, R and Davids, M and Pedersen, HK and Nielsen, HB and Groen, AK and de Vos, WM and van Laarhoven, HWM and Nieuwdorp, M}, title = {Fecal Microbiota Transplantation from Overweight or Obese Donors in Cachectic Patients with Advanced Gastroesophageal Cancer: A Randomized, Double-blind, Placebo-Controlled, Phase II Study.}, journal = {Clinical cancer research : an official journal of the American Association for Cancer Research}, volume = {27}, number = {13}, pages = {3784-3792}, doi = {10.1158/1078-0432.CCR-20-4918}, pmid = {33883174}, issn = {1557-3265}, mesh = {Adult ; Aged ; Cachexia/*etiology/microbiology/*therapy ; Double-Blind Method ; Esophageal Neoplasms/*complications/microbiology/pathology ; *Fecal Microbiota Transplantation ; Female ; *Gastrointestinal Microbiome ; Humans ; Male ; Middle Aged ; Neoplasm Staging ; Obesity/microbiology ; Overweight/microbiology ; Stomach Neoplasms/*complications/microbiology/pathology ; }, abstract = {PURPOSE: Cachexia is a multifactorial syndrome, associated with poor survival in patients with cancer, and is influenced by the gut microbiota. We investigated the effects of fecal microbiota transplantation (FMT) on cachexia and treatment response in patients with advanced gastroesophageal cancer.<br><br>EXPERIMENTAL DESIGN: In a double-blind randomized placebo-controlled trial performed in the Amsterdam University Medical Center, we assigned 24 cachectic patients with metastatic HER2-negative gastroesophageal cancer to either allogenic FMT (healthy obese donor) or autologous FMT, prior to palliative chemotherapy (capecitabine and oxaliplatin). Primary objective was to assess the effect of allogenic FMT on satiety. Secondary outcomes were other features of cachexia, along with disease control rate (DCR), overall survival (OS), progression-free survival (PFS), and toxicity. Finally, exploratory analyses were performed on the effect of FMT on gut microbiota composition (metagenomic sequencing) and metabolites (untargeted metabolomics).<br><br>RESULTS: Allogenic FMT did not improve any of the cachexia outcomes. Patients in the allogenic group (n = 12) had a higher DCR at 12 weeks (P = 0.035) compared with the autologous group (n = 12), longer median OS of 365 versus 227 days [HR = 0.38; 95% confidence interval (CI), 0.14-1.05; P = 0.057] and PFS of 204 versus 93 days (HR = 0.50; 95% CI, 0.21-1.20; P = 0.092). Patients in the allogenic group showed a significant shift in fecal microbiota composition after FMT (P = 0.010) indicating proper engraftment of the donor microbiota.<br><br>CONCLUSIONS: FMT from a healthy obese donor prior to first-line chemotherapy did not affect cachexia, but may have improved response and survival in patients with metastatic gastroesophageal cancer. These results provide a rational for larger FMT trials.}, }
@article {pmid33880763, year = {2021}, author = {Zhang, W and Chen, X and Wong, KC}, title = {Noninvasive early diagnosis of intestinal diseases based on artificial intelligence in genomics and microbiome.}, journal = {Journal of gastroenterology and hepatology}, volume = {36}, number = {4}, pages = {823-831}, doi = {10.1111/jgh.15500}, pmid = {33880763}, issn = {1440-1746}, support = {CityU 11203520//City University of Hong Kong/ ; CityU 11202219//City University of Hong Kong/ ; 07181426//Health and Medical Research Fund, Food and Health Bureau/ ; CityU 11200218//Research Grants Council, University Grants Committee/ ; }, mesh = {Diagnostic Techniques, Digestive System/*trends ; *Early Diagnosis ; Genomics/*methods ; High-Throughput Nucleotide Sequencing/methods/trends ; Humans ; Intestinal Diseases/*diagnosis ; Machine Learning/*trends ; }, abstract = {The maturing development in artificial intelligence (AI) and genomics has propelled the advances in intestinal diseases including intestinal cancer, inflammatory bowel disease (IBD), and irritable bowel syndrome (IBS). On the other hand, colorectal cancer is the second most deadly and the third most common type of cancer in the world according to GLOBOCAN 2020 data. The mechanisms behind IBD and IBS are still speculative. The conventional methods to identify colorectal cancer, IBD, and IBS are based on endoscopy or colonoscopy to identify lesions. However, it is invasive, demanding, and time-consuming for early-stage intestinal diseases. To address those problems, new strategies based on blood and/or human microbiome in gut, colon, or even feces were developed; those methods took advantage of high-throughput sequencing and machine learning approaches. In this review, we summarize the recent research and methods to diagnose intestinal diseases with machine learning technologies based on cell-free DNA and microbiome data generated by amplicon sequencing or whole-genome sequencing. Those methods play an important role in not only intestinal disease diagnosis but also therapy development in the near future.}, }
@article {pmid33872639, year = {2021}, author = {Strobbe, F and Bénard, MV and Rossen, NG and de Vos, WM and Kumar, N and Lawley, TD and Zoetendal, EG and Hugenholtz, F and Ponsioen, CY}, title = {A novel technique capable of taking 'protected' biopsies for reliable assessment of the distribution of microbiota along the colonic mucosa.}, journal = {Journal of microbiological methods}, volume = {185}, number = {}, pages = {106204}, doi = {10.1016/j.mimet.2021.106204}, pmid = {33872639}, issn = {1872-8359}, mesh = {Adult ; Aged ; Anemia, Iron-Deficiency ; Biopsy/instrumentation/*methods ; Colon/*microbiology ; Female ; Gastrointestinal Microbiome/genetics/*physiology ; Humans ; Intestinal Mucosa/*microbiology ; Male ; Middle Aged ; RNA, Ribosomal, 16S ; Specimen Handling/methods ; }, abstract = {We evaluated a novel 'protected' biopsy method to reliably ascertain the spatial distribution of the mucosa-adherent colonic microbiota. Apart from minor differences at genus level, overall similarities along the colon were high between the various areas, irrespective of protected or unprotected sampling.}, }
@article {pmid33872488, year = {2021}, author = {Kang, HM and Kang, JH}, title = {Effects of nasopharyngeal microbiota in respiratory infections and allergies.}, journal = {Clinical and experimental pediatrics}, volume = {64}, number = {11}, pages = {543-551}, pmid = {33872488}, issn = {2713-4148}, abstract = {The human microbiome, which consists of a collective cluster of commensal, symbiotic, and pathogenic microorganisms living in the human body, plays a key role in host health and immunity. The human nasal cavity harbors commensal bacteria that suppress the colonization of opportunistic pathogens. However, dysbiosis of the nasal microbial community is associated with many diseases, such as acute respiratory infections including otitis media, sinusitis and bronchitis and allergic respiratory diseases including asthma. The nasopharyngeal acquisition of pneumococcus, which exists as a pathobiont in the nasal cavity, is the initial step in virtually all pneumococcal diseases. Although the factors influencing nasal colonization and elimination are not fully understood, the adhesion of opportunistic pathogens to nasopharyngeal mucosa receptors and the eliciting of immune responses in the host are implicated in addition to bacterial microbiota properties and colonization resistance dynamics. Probiotics or synbiotic interventions may show promising and effective roles in the adjunctive treatment of dysbiosis; however, more studies are needed to characterize how these interventions can be applied in clinical practice in the future.}, }
@article {pmid33865678, year = {2021}, author = {Petrova, MI and Reid, G and Ter Haar, JA}, title = {Lacticaseibacillus rhamnosus GR-1, a.k.a. Lactobacillus rhamnosus GR-1: Past and Future Perspectives.}, journal = {Trends in microbiology}, volume = {29}, number = {8}, pages = {747-761}, doi = {10.1016/j.tim.2021.03.010}, pmid = {33865678}, issn = {1878-4380}, mesh = {Animals ; CD4 Lymphocyte Count ; Female ; Humans ; Lacticaseibacillus rhamnosus/genetics/*immunology/*metabolism ; Probiotics/*therapeutic use ; Urinary Tract Infections/microbiology ; Vagina/*microbiology ; Vaginosis, Bacterial ; Women's Health ; }, abstract = {Lacticaseibacillus rhamnosus GR-1 (LGR-1) (previously classified as Lactobacillus rhamnosus GR-1) is the most researched probiotic strain for women's health. Its various urogenital health effects, including a reduction in the recurrence of bacterial vaginosis and urinary-tract infection, are well documented. The strain has also been safely used by HIV-positive subjects, a portion of whom have reported reduced diarrhea and increased CD4 counts. Unlike most probiotic strains used for urogenital health, LGR-1 has been extensively studied for its properties, including its genomic and metabolic traits and its surface properties. This review aims to highlight the totality of research performed with LGR-1, to act as a rigorous scientific benchmark for probiotic microbes, especially for application to women's health.}, }
@article {pmid33856544, year = {2021}, author = {Lu, H and Yao, Y and Yang, J and Zhang, H and Li, L}, title = {Microbiome-miRNA interactions in the progress from undifferentiated arthritis to rheumatoid arthritis: evidence, hypotheses, and opportunities.}, journal = {Rheumatology international}, volume = {41}, number = {9}, pages = {1567-1575}, pmid = {33856544}, issn = {1437-160X}, support = {81874038//National Natural Science Foundation of China/ ; 81501431//National Natural Science Foundation of China/ ; 81600506//National Natural Science Foundation of China/ ; 81672422//National Natural Science Foundation of China/ ; }, mesh = {Arthritis, Rheumatoid/immunology/metabolism/*microbiology ; Disease Progression ; Dysbiosis/*immunology ; Gastrointestinal Microbiome ; Humans ; MicroRNAs/*immunology ; }, abstract = {The human microbiome has attracted attention for its potential utility in precision medicine. Increasingly, more researchers are recognizing changes in intestinal microbiome can upset the balance between pro- and anti-inflammatory factors of host immune system, potentially contributing to arthritis immunopathogenesis. Patients who develop rheumatoid arthritis from undifferentiated arthritis can face multiple irreversible joint lesions and even deformities. Strategies for identifying undifferentiated arthritis patients who have a tendency to develop rheumatoid arthritis and interventions to prevent rheumatoid arthritis development are urgently needed. Intestinal microbiome dysbiosis and shifts in the miRNA profile affect undifferentiated arthritis progression, and may play an important role in rheumatoid arthritis pathophysiologic process via stimulating inflammatory cytokines and disturbing host and microbial metabolic functions. However, a causal relationship between microbiome-miRNA interactions and rheumatoid arthritis development from undifferentiated arthritis has not been uncovered yet. Changes in the intestinal microbiome and miRNA profiles of undifferentiated arthritis patients with different disease outcomes should be studied together to uncover the role of the intestinal microbiome in rheumatoid arthritis development and to identify potential prognostic indicators of rheumatoid arthritis in undifferentiated arthritis patients. Herein, we discuss the possibility of microbiome-miRNA interactions contributing to rheumatoid arthritis development and describe the gaps in knowledge regarding their influence on undifferentiated arthritis prognosis that should be addressed by future studies.}, }
@article {pmid33856143, year = {2022}, author = {Maslennikov, R and Ivashkin, V and Ufimtseva, A and Poluektova, E}, title = {A clinical variant of Coronavirus disease 2019 with diarrhea as the initial symptom compared with other variants.}, journal = {Minerva gastroenterology}, volume = {68}, number = {4}, pages = {487-489}, doi = {10.23736/S2724-5985.21.02827-0}, pmid = {33856143}, issn = {2724-5365}, mesh = {Humans ; *COVID-19/complications ; *Porcine epidemic diarrhea virus ; Diarrhea/etiology ; }, }
@article {pmid33848761, year = {2021}, author = {Johns, MS and Petrelli, NJ}, title = {Microbiome and colorectal cancer: A review of the past, present, and future.}, journal = {Surgical oncology}, volume = {37}, number = {}, pages = {101560}, doi = {10.1016/j.suronc.2021.101560}, pmid = {33848761}, issn = {1879-3320}, mesh = {Colorectal Neoplasms/*etiology/metabolism/pathology ; Gastrointestinal Microbiome/*physiology ; Humans ; }, abstract = {The gastrointestinal tract is home to diverse and abundant microorganisms, collectively referred to as the microbiome. This ecosystem typically contains trillions of microbial cells that play an important role in regulation of human health. The microbiome has been implicated in host immunity, nutrient absorption, digestion, and metabolism. In recent years, researchers have shown that alteration of the microbiome is associated with disease development, such as obesity, inflammatory bowel disease, and cancer. This review discusses the five decades of research into the human microbiome and the development of colorectal cancer - the historical context including experiments that sparked interest, the explosion of research that has occurred in the last decade, and finally the future of testing and treatment.}, }
@article {pmid33846857, year = {2021}, author = {Classen, AY and Henze, L and von Lilienfeld-Toal, M and Maschmeyer, G and Sandherr, M and Graeff, LD and Alakel, N and Christopeit, M and Krause, SW and Mayer, K and Neumann, S and Cornely, OA and Penack, O and Weißinger, F and Wolf, HH and Vehreschild, JJ}, title = {Primary prophylaxis of bacterial infections and Pneumocystis jirovecii pneumonia in patients with hematologic malignancies and solid tumors: 2020 updated guidelines of the Infectious Diseases Working Party of the German Society of Hematology and Medical Oncology (AGIHO/DGHO).}, journal = {Annals of hematology}, volume = {100}, number = {6}, pages = {1603-1620}, pmid = {33846857}, issn = {1432-0584}, mesh = {Anti-Bacterial Agents/*therapeutic use ; Antineoplastic Agents/therapeutic use ; Drug Resistance, Bacterial ; Fluoroquinolones/therapeutic use ; Germany ; Hematologic Neoplasms/*complications/drug therapy ; Hematology ; Humans ; Medical Oncology ; Microbiota/drug effects ; Pneumocystis carinii/*drug effects ; Pneumonia, Pneumocystis/complications/*prevention &amp; control ; Societies, Medical ; }, abstract = {Hematologic and oncologic patients with chemo- or immunotherapy-related immunosuppression are at substantial risk for bacterial infections and Pneumocystis jirovecii pneumonia (PcP). As bacterial resistances are increasing worldwide and new research reshapes our understanding of the interactions between the human host and bacterial commensals, administration of antibacterial prophylaxis has become a matter of discussion. This guideline constitutes an update of the 2013 published guideline of the Infectious Diseases Working Party (AGIHO) of the German Society for Hematology and Medical Oncology (DGHO). It gives an overview about current strategies for antibacterial prophylaxis in cancer patients while taking into account the impact of antibacterial prophylaxis on the human microbiome and resistance development. Current literature published from January 2012 to August 2020 was searched and evidence-based recommendations were developed by an expert panel. All recommendations were discussed and approved in a consensus conference of the AGIHO prior to publication. As a result, we present a comprehensive update and extension of our guideline for antibacterial and PcP prophylaxis in cancer patients.}, }
@article {pmid33845877, year = {2021}, author = {Guerin, E and Shkoporov, AN and Stockdale, SR and Comas, JC and Khokhlova, EV and Clooney, AG and Daly, KM and Draper, LA and Stephens, N and Scholz, D and Ross, RP and Hill, C}, title = {Isolation and characterisation of ΦcrAss002, a crAss-like phage from the human gut that infects Bacteroides xylanisolvens.}, journal = {Microbiome}, volume = {9}, number = {1}, pages = {89}, pmid = {33845877}, issn = {2049-2618}, mesh = {*Bacteriophages/genetics ; Bacteroides ; *Gastrointestinal Microbiome ; Humans ; Phylogeny ; }, abstract = {BACKGROUND: The gut phageome comprises a complex phage community of thousands of individual strains, with a few highly abundant bacteriophages. CrAss-like phages, which infect bacteria of the order Bacteroidales, are the most abundant bacteriophage family in the human gut and make an important contribution to an individual's core virome. Based on metagenomic data, crAss-like phages form a family, with four sub-families and ten candidate genera. To date, only three representatives isolated in pure culture have been reported: ΦcrAss001 and two closely related phages DAC15 and DAC17; all are members of the less abundant candidate genus VI. The persistence at high levels of both crAss-like phage and their Bacteroidales hosts in the human gut has not been explained mechanistically, and this phage-host relationship can only be properly studied with isolated phage-host pairs from as many genera as possible.<br><br>RESULTS: Faeces from a healthy donor with high levels of crAss-like phage was used to initiate a faecal fermentation in a chemostat, with selected antibiotics chosen to inhibit rapidly growing bacteria and selectively enrich for Gram-negative Bacteroidales. This had the objective of promoting the simultaneous expansion of crAss-like phages on their native hosts. The levels of seven different crAss-like phages expanded during the fermentation, indicating that their hosts were also present in the fermenter. The enriched supernatant was then tested against individual Bacteroidales strains isolated from the same faecal sample. This resulted in the isolation of a previously uncharacterised crAss-like phage of candidate genus IV of the proposed Alphacrassvirinae sub-family, &#x3a6;crAss002, that infects the gut commensal Bacteroides xylanisolvens. &#x3a6;crAss002 does not form plaques or spots on lawns of sensitive cells, nor does it lyse liquid cultures, even at high titres. In keeping with the co-abundance of phage and host in the human gut, &#x3a6;crAss002 and Bacteroides xylanisolvens can also co-exist at high levels when co-cultured in laboratory media.<br><br>CONCLUSIONS: We report the isolation and characterisation of &#x3a6;crAss002, the first representative of the proposed Alphacrassvirinae sub-family of crAss-like phages. &#x3a6;crAss002 cannot form plaques or spots on bacterial lawns but can co-exist with its host, Bacteroides xylanisolvens, at very high levels in liquid culture without impacting on bacterial numbers. Video abstract.}, }
@article {pmid33845850, year = {2021}, author = {Fremin, BJ and Bhatt, AS}, title = {Comparative genomics identifies thousands of candidate structured RNAs in human microbiomes.}, journal = {Genome biology}, volume = {22}, number = {1}, pages = {100}, pmid = {33845850}, issn = {1474-760X}, support = {R01 AI148623/AI/NIAID NIH HHS/United States ; 1S10OD02014101/CA/NCI NIH HHS/United States ; U24 AG021886/AG/NIA NIH HHS/United States ; P30 AG066515/AG/NIA NIH HHS/United States ; P50AG047366/NH/NIH HHS/United States ; P50 AG047366/AG/NIA NIH HHS/United States ; }, mesh = {Computational Biology/methods ; Gastrointestinal Microbiome ; *Genomics/methods ; Humans ; *Metagenome ; *Metagenomics/methods ; *Microbiota ; Nucleic Acid Conformation ; RNA ; Workflow ; }, abstract = {BACKGROUND: Structured RNAs play varied bioregulatory roles within microbes. To date, hundreds of candidate structured RNAs have been predicted using informatic approaches that search for motif structures in genomic sequence data. The human microbiome contains thousands of species and strains of microbes. Yet, much of the metagenomic data from the human microbiome remains unmined for structured RNA motifs primarily due to computational limitations.<br><br>RESULTS: We sought to apply a large-scale, comparative genomics approach to these organisms to identify candidate structured RNAs. With a carefully constructed, though computationally intensive automated analysis, we identify 3161 conserved candidate structured RNAs in intergenic regions, as well as 2022 additional candidate structured RNAs that may overlap coding regions. We validate the RNA expression of 177 of these candidate structures by analyzing small fragment RNA-seq data from four human fecal samples.<br><br>CONCLUSIONS: This approach identifies a wide variety of candidate structured RNAs, including tmRNAs, antitoxins, and likely ribosome protein leaders, from a wide variety of taxa. Overall, our pipeline enables conservative predictions of thousands of novel candidate structured RNAs from human microbiomes.}, }
@article {pmid33837018, year = {2021}, author = {Thomas, AM and Asnicar, F and Kroemer, G and Segata, N}, title = {Genes Encoding Microbial Acyl Coenzyme A Binding Protein/Diazepam-Binding Inhibitor Orthologs Are Rare in the Human Gut Microbiome and Show No Links to Obesity.}, journal = {Applied and environmental microbiology}, volume = {87}, number = {12}, pages = {e0047121}, pmid = {33837018}, issn = {1098-5336}, support = {R01 CA230551/CA/NCI NIH HHS/United States ; U01 CA230551/CA/NCI NIH HHS/United States ; }, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Bacterial Proteins/*genetics ; Body Mass Index ; Burkholderiaceae/genetics ; Comamonas/genetics ; Diazepam Binding Inhibitor/*genetics ; Female ; Gastrointestinal Microbiome/*genetics ; Humans ; Male ; Middle Aged ; Obesity/*microbiology ; Saccharomyces cerevisiae/genetics ; Young Adult ; }, abstract = {Acyl coenzyme A (CoA) binding protein (ACBP), also called diazepam-binding inhibitor (DBI), is a phylogenetically conserved protein that is expressed by all eukaryotic species as well as by some bacteria. Since elevated ACBP/DBI levels play a major role in the inhibition of autophagy, increase in appetite, and enhanced lipid storage that accompany obesity, we wondered whether ACBP/DBI produced by the human microbiome might affect host weight. We found that the genomes of bacterial commensals rarely contain ACBP/DBI homologues, which are rather encoded by genomes of some pathogenic or environmental taxa that were not prevalent in human feces. Exhaustive bioinformatic analyses of 1,899 gut samples from healthy individuals refuted the hypothesis that bacterial ACBP/DBI might affect the body mass index (BMI) in a physiological context. Thus, the physiological regulation of BMI is unlikely to be affected by microbial ACBP/DBI-like proteins. However, at the speculative level, it remains possible that ACBP/DBI produced by potential pathogenic bacteria might enhance their virulence by inhibiting autophagy and hence subverting innate immune responses. IMPORTANCE Acyl coenzyme A (CoA) binding protein (ACBP) can be encoded by several organisms across the domains of life, including microbes, and has shown to play major roles in human metabolic processes. However, little is known about its presence in the human gut microbiome and whether its microbial counterpart could also play a role in human metabolism. In the present study, we found that microbial ACBP/DBI sequences were rarely present in the gut microbiome across multiple metagenomic data sets. Microbes that carried ACBP/DBI in the human gut microbiome included Saccharomyces cerevisiae, Lautropia mirabilis, and Comamonas kerstersii, but these microorganisms were not associated with body mass index, further indicating an unconvincing role for microbial ACBP/DBI in human metabolism.}, }
@article {pmid33836617, year = {2021}, author = {}, title = {Correction for Finlay et al., The hygiene hypothesis, the COVID pandemic, and consequences for the human microbiome.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {118}, number = {11}, pages = {}, doi = {10.1073/pnas.2102333118}, pmid = {33836617}, issn = {1091-6490}, }
@article {pmid33833745, year = {2021}, author = {Singh, H and Clarke, T and Brinkac, L and Greco, C and Nelson, KE}, title = {Forensic Microbiome Database: A Tool for Forensic Geolocation Meta-Analysis Using Publicly Available 16S rRNA Microbiome Sequencing.}, journal = {Frontiers in microbiology}, volume = {12}, number = {}, pages = {644861}, pmid = {33833745}, issn = {1664-302X}, abstract = {The human microbiome has been proposed as a tool to investigate different forensic questions, including for the identification of multiple personal information. However, the fragmented state of the publicly available data has retarded the development of analysis techniques and, therefore, the implementation of microbiomes as a forensic tool. To address this, we introduce the forensic microbiome database (FMD), which is a collection of 16S rRNA data and associated metadata generated from publicly available data. The raw data was further normalized and processed using a pipeline to create a standardized data set for downstream analysis. We present a website allowing for the exploration of geolocation signals in the FMD. The website allows users to investigate the taxonomic differences between microbiomes harvested from different locations and to predict the geolocation of their data based on the FMD sequences. All the results are presented in dynamic graphics to allow for a rapid and intuitive investigation of the taxonomic distributions underpinning the geolocation signals and prediction between locations. Apart from the forensic aspect, the database also allows exploration and comparison of microbiome samples from different geolocation and between different body sites. The goal of the FMD is to provide the scientific and non-scientific communities with data and tools to explore the possibilities of microbiomes to answer forensic questions and serve as a model for any future such databases.}, }
@article {pmid33829521, year = {2021}, author = {Catania, F and Baedke, J and Fábregas-Tejeda, A and Nieves Delgado, A and Vitali, V and Long, LAN}, title = {Global climate change, diet, and the complex relationship between human host and microbiome: Towards an integrated picture.}, journal = {BioEssays : news and reviews in molecular, cellular and developmental biology}, volume = {43}, number = {6}, pages = {e2100049}, doi = {10.1002/bies.202100049}, pmid = {33829521}, issn = {1521-1878}, mesh = {Climate Change ; Diet ; Dysbiosis ; Humans ; *Life History Traits ; *Microbiota ; }, abstract = {Dietary changes can alter the human microbiome with potential detrimental consequences for health. Given that environment, health, and evolution are interconnected, we ask: Could diet-driven microbiome perturbations have consequences that extend beyond their immediate impact on human health? We address this question in the context of the urgent health challenges posed by global climate change. Drawing on recent studies, we propose that not only can diet-driven microbiome changes lead to dysbiosis, they can also shape life-history traits and fuel human evolution. We posit that dietary shifts prompt mismatched microbiome-host genetics configurations that modulate human longevity and reproductive success. These mismatches can also induce a heritable intra-holobiont stress response, which encourages the holobiont to re-establish equilibrium within the changed nutritional environment. Thus, while mismatches between climate change-related genetic and epigenetic configurations within the holobiont increase the risk and severity of diseases, they may also affect life-history traits and facilitate adaptive responses. These propositions form a framework that can help systematize and address climate-related dietary challenges for policy and health interventions.}, }
@article {pmid33828922, year = {2021}, author = {Solanki, V and Tiwari, M and Tiwari, V}, title = {Immunoinformatic approach to design a multiepitope vaccine targeting non-mutational hotspot regions of structural and non-structural proteins of the SARS CoV2.}, journal = {PeerJ}, volume = {9}, number = {}, pages = {e11126}, pmid = {33828922}, issn = {2167-8359}, abstract = {BACKGROUND: The rapid Severe Acute Respiratory Syndrome Coronavirus 2 (SARS CoV2) outbreak caused severe pandemic infection worldwide. The high mortality and morbidity rate of SARS CoV2 is due to the unavailability of vaccination and mutation in this virus. The present article aims to design a potential vaccine construct VTC3 targeting the non-mutational region of structural and non-structural proteins of SARS CoV2.<br><br>METHODS: In this study, vaccines were designed using subtractive proteomics and reverse vaccinology. To target the virus adhesion and evasion, 10 different structural and non-structural proteins have been selected. Shortlisted proteins have been screened for B cell, T cell and IFN gamma interacting epitopes. 3D structure of vaccine construct was modeled and evaluated for its physicochemical properties, immunogenicity, allergenicity, toxicity and antigenicity. The finalized construct was implemented for docking and molecular dynamics simulation (MDS) with different toll-like receptors (TLRs) and human leukocyte antigen (HLA). The binding energy and dissociation construct of the vaccine with HLA and TLR was also calculated. Mutational sensitivity profiling of the designed vaccine was performed, and mutations were reconfirmed from the experimental database. Antibody production, clonal selection, antigen processing, immune response and memory generation in host cells after injection of the vaccine was also monitored using immune simulation.<br><br>RESULTS: Subtractive proteomics identified seven (structural and non-structural) proteins of this virus that have a role in cell adhesion and infection. The different epitopes were predicted, and only extracellular epitopes were selected that do not have similarity and cross-reactivity with the host cell. Finalized epitopes of all proteins with minimum allergenicity and toxicity were joined using linkers to designed different vaccine constructs. Docking different constructs with different TLRs and HLA demonstrated a stable and reliable binding affinity of VTC3 with the TLRs and HLAs. MDS analysis further confirms the interaction of VTC3 with HLA and TLR1/2 complex. The VTC3 has a favorable binding affinity and dissociation constant with HLA and TLR. The VTC3 does not have similarities with the human microbiome, and most of the interacting residues of VTC3 do not have mutations. The immune simulation result showed that VTC3 induces a strong immune response. The present study designs a multiepitope vaccine targeting the non-mutational region of structural and non-structural proteins of the SARS CoV2 using an immunoinformatic approach, which needs to be experimentally validated.}, }
@article {pmid33824193, year = {2021}, author = {Daisley, BA and Reid, G}, title = {BEExact: a Metataxonomic Database Tool for High-Resolution Inference of Bee-Associated Microbial Communities.}, journal = {mSystems}, volume = {6}, number = {2}, pages = {}, pmid = {33824193}, issn = {2379-5077}, abstract = {High-throughput 16S rRNA gene sequencing technologies have robust potential to improve our understanding of bee (Hymenoptera: Apoidea)-associated microbial communities and their impact on hive health and disease. Despite recent computation algorithms now permitting exact inferencing of high-resolution exact amplicon sequence variants (ASVs), the taxonomic classification of these ASVs remains a challenge due to inadequate reference databases. To address this, we assemble a comprehensive data set of all publicly available bee-associated 16S rRNA gene sequences, systematically annotate poorly resolved identities via inclusion of 618 placeholder labels for uncultivated microbial dark matter, and correct for phylogenetic inconsistencies using a complementary set of distance-based and maximum likelihood correction strategies. To benchmark the resultant database (BEExact), we compare performance against all existing reference databases in silico using a variety of classifier algorithms to produce probabilistic confidence scores. We also validate realistic classification rates on an independent set of ∼234 million short-read sequences derived from 32 studies encompassing 50 different bee types (36 eusocial and 14 solitary). Species-level classification rates on short-read ASVs range from 80 to 90% using BEExact (with ∼20% due to "bxid" placeholder names), whereas only ∼30% at best can be resolved with current universal databases. A series of data-driven recommendations are developed for future studies. We conclude that BEExact (https://github.com/bdaisley/BEExact) enables accurate and standardized microbiota profiling across a broad range of bee species-two factors of key importance to reproducibility and meaningful knowledge exchange within the scientific community that together, can enhance the overall utility and ecological relevance of routine 16S rRNA gene-based sequencing endeavors.IMPORTANCE The failure of current universal taxonomic databases to support the rapidly expanding field of bee microbiota research has led to many investigators relying on "in-house" reference sets or manual classification of sequence reads (usually based on BLAST searches), often with vague identity thresholds and subjective taxonomy choices. This time-consuming, error- and bias-prone process lacks standardization, cripples the potential for comparative cross-study analysis, and in many cases is likely to incorrectly sway study conclusions. BEExact is structured on and leverages several complementary bioinformatic techniques to enable refined inference of bee host-associated microbial communities without any other methodological modifications necessary. It also bridges the gap between current practical outcomes (i.e., phylotype-to-genus level constraints with 97% operational taxonomic units [OTUs]) and the theoretical resolution (i.e., species-to-strain level classification with 100% ASVs) attainable in future microbiota investigations. Other niche habitats could also likely benefit from customized database curation via implementation of the novel approaches introduced in this study.}, }
@article {pmid33821248, year = {2021}, author = {Kantele, A and Kuenzli, E and Dunn, SJ and Dance, DAB and Newton, PN and Davong, V and Mero, S and Pakkanen, SH and Neumayr, A and Hatz, C and Snaith, A and Kallonen, T and Corander, J and McNally, A}, title = {Dynamics of intestinal multidrug-resistant bacteria colonisation contracted by visitors to a high-endemic setting: a prospective, daily, real-time sampling study.}, journal = {The Lancet. Microbe}, volume = {2}, number = {4}, pages = {e151-e158}, pmid = {33821248}, issn = {2666-5247}, support = {MRS0136601/MRC_/Medical Research Council/United Kingdom ; MR/S013660/1/MRC_/Medical Research Council/United Kingdom ; BBR0062611/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; /WT_/Wellcome Trust/United Kingdom ; 108876B15Z/WT_/Wellcome Trust/United Kingdom ; }, mesh = {*Anti-Bacterial Agents/pharmacology ; Bacteria ; *Drug Resistance, Multiple, Bacterial/genetics ; Humans ; Prospective Studies ; Sampling Studies ; }, abstract = {BACKGROUND: Antimicrobial resistance is highly prevalent in low-income and middle-income countries. International travel contributes substantially to the global spread of intestinal multidrug-resistant Gram-negative bacteria. Hundreds of millions of annual visitors to low-income and middle-income countries are all exposed to intestinal multidrug-resistant Gram-negative bacteria resulting in 30-70% of them being colonised at their return. The colonisation process in high-exposure environments is poorly documented because data have only been derived from before travel and after travel sampling. We characterised colonisation dynamics by exploring daily stool samples while visiting a low-income and middle-income countries.<br><br>METHODS: In this prospective, daily, real-time sampling study 20 European visitors to Laos volunteered to provide daily stool samples and completed daily questionnaires for 22 days. Samples were initially assessed at Mahosot Hospital, Vientiane, Laos, for acquisition of extended-spectrum &#x3b2;-lactamase-producing (ESBL) Gram-negative bacteria followed by whole-genome sequencing of isolates at MicrobesNG, University of Birmingham, Birmingham, UK. The primary outcome of the study was to obtain data on the dynamics of intestinal multidrug-resistant bacteria acquisition.<br><br>FINDINGS: Between Sept 18 and Sept 20, 2015, 23 volunteers were recruited, of whom 20 (87%) European volunteers were included in the final study population. Although colonisation rates were 70% at the end of the study, daily sampling revealed that all participants had acquired ESBL-producing Gram-negative bacteria at some point during the study period; the colonisation status varied day by day. Whole-genome sequencing analysis ascribed the transient pattern of colonisation to sequential acquisition of new strains, resulting in a loss of detectable colonisation by the initial multidrug-resistant Gram-negative strains. 19 (95%) participants acquired two to seven strains. Of the 83 unique strains identified (53 Escherichia coli, 10 Klebsiella spp, and 20 other ESBL-producing Gram-negative bacteria), some were shared by as many as four (20%) participants.<br><br>INTERPRETATION: To our knowledge, this is the first study to characterise in real-time the dynamics of acquiring multidrug-resistant Gram-negative bacterial colonisation during travel. Our data show multiple transient colonisation events indicative of constant microbial competition and suggest that travellers are exposed to a greater burden of multidrug-resistant bacteria than previously thought. The data emphasise the need for preventing travellers' diarrhoea and limiting antibiotic use, addressing the two major factors predisposing colonisation.<br><br>FUNDING: The Finnish Governmental Subsidy for Health Science Research, The Scandinavian Society for Antimicrobial Chemotherapy, the Sigrid Jus&#xe9;lius Foundation, Biotechnology and Biological Sciences Research Council; Wellcome Trust, Medical Research Council; The Royal Society; Joint Programming Initiative on Antimicrobial Resistance, and European Research Council.}, }
@article {pmid33820996, year = {2021}, author = {Wilkinson, JE and Franzosa, EA and Everett, C and Li, C and ,  and ,  and Hu, FB and Wirth, DF and Song, M and Chan, AT and Rimm, E and Garrett, WS and Huttenhower, C}, title = {A framework for microbiome science in public health.}, journal = {Nature medicine}, volume = {27}, number = {5}, pages = {766-774}, pmid = {33820996}, issn = {1546-170X}, support = {C10674/A27140/CRUK_/Cancer Research UK/United Kingdom ; 27140/CRUK_/Cancer Research UK/United Kingdom ; /HHMI/Howard Hughes Medical Institute/United States ; P30 DK046200/DK/NIDDK NIH HHS/United States ; R24 DK110499/DK/NIDDK NIH HHS/United States ; R01 NS097723/NS/NINDS NIH HHS/United States ; }, mesh = {Biomedical Research/*methods ; Fecal Microbiota Transplantation/methods ; Gastrointestinal Microbiome/*physiology ; Health Status ; Humans ; Prebiotics/administration &amp; dosage ; Probiotics/therapeutic use ; Public Health/education/*methods ; }, abstract = {Human microbiome science has advanced rapidly and reached a scale at which basic biology, clinical translation and population health are increasingly integrated. It is thus now possible for public health researchers, practitioners and policymakers to take specific action leveraging current and future microbiome-based opportunities and best practices. Here we provide an outline of considerations for research, education, interpretation and scientific communication concerning the human microbiome and public health. This includes guidelines for population-scale microbiome study design; necessary physical platforms and analysis methods; integration into public health areas such as epidemiology, nutrition, chronic disease, and global and environmental health; entrepreneurship and technology transfer; and educational curricula. Particularly in the near future, there are both opportunities for the incorporation of microbiome-based technologies into public health practice, and a growing need for policymaking and regulation around related areas such as prebiotic and probiotic supplements, novel live-cell therapies and fecal microbiota transplants.}, }
@article {pmid33816940, year = {2020}, author = {Dias, CK and Starke, R and Pylro, VS and Morais, DK}, title = {Database limitations for studying the human gut microbiome.}, journal = {PeerJ. Computer science}, volume = {6}, number = {}, pages = {e289}, pmid = {33816940}, issn = {2376-5992}, abstract = {BACKGROUND: In the last twenty years, new methodologies have made possible the gathering of large amounts of data concerning the genetic information and metabolic functions associated to the human gut microbiome. In spite of that, processing all this data available might not be the simplest of tasks, which could result in an excess of information awaiting proper annotation. This assessment intended on evaluating how well respected databases could describe a mock human gut microbiome.<br><br>METHODS: In this work, we critically evaluate the output of the cross-reference between the Uniprot Knowledge Base (Uniprot KB) and the Kyoto Encyclopedia of Genes and Genomes Orthologs (KEGG Orthologs) or the evolutionary genealogy of genes: Non-supervised Orthologous groups (EggNOG) databases regarding a list of species that were previously found in the human gut microbiome.<br><br>RESULTS: From a list which contemplates 131 species and 52 genera, 53 species and 40 genera had corresponding entries for KEGG Database and 82 species and 47 genera had corresponding entries for EggNOG Database. Moreover, we present the KEGG Orthologs (KOs) and EggNOG Orthologs (NOGs) entries associated to the search as their distribution over species and genera and lists of functions that appeared in many species or genera, the "core" functions of the human gut microbiome. We also present the relative abundance of KOs and NOGs throughout phyla and genera. Lastly, we expose a variance found between searches with different arguments on the database entries. Inferring functionality based on cross-referencing UniProt and KEGG or EggNOG can be lackluster due to the low number of annotated species in Uniprot and due to the lower number of functions affiliated to the majority of these species. Additionally, the EggNOG database showed greater performance for a cross-search with Uniprot about a mock human gut microbiome. Notwithstanding, efforts targeting cultivation, single-cell sequencing or the reconstruction of high-quality metagenome-assembled genomes (MAG) and their annotation are needed to allow the use of these databases for inferring functionality in human gut microbiome studies.}, }
@article {pmid35492394, year = {2021}, author = {Marshall, EA and Telkar, N and Lam, WL}, title = {Functional role of the cancer microbiome in the solid tumour niche.}, journal = {Current research in immunology}, volume = {2}, number = {}, pages = {1-6}, pmid = {35492394}, issn = {2590-2555}, abstract = {The importance of gut microbiome to cancer therapy and response cannot be overstated, however the contribution of the bacterial population to the local solid tumour ecosystem is often overlooked. Seminal studies of tumour-resident microbiomes have shown that relative abundances of specific bacteria in the tumour correlate with survival metrics, implicating the microbiome in patient outcome. Similarly, patterns of microbiome community shifts between tumour-bearing and unaffected organs suggests a role for the tumour microbiome niche in contributing to tumour biology and behaviour. Recent reports of the detection of bacteria in solid tumours of diverse human organs have provided a strong rationale for deciphering the role of the solid-tumour microbiome across all human-host anatomic and physiologic niches, as the microbiome is ubiquitously present throughout the human body. Here, we review the role of the human microbiome in mediating response to therapies, as well as the differences between tumour and non-malignant-resident communities. We discuss the ability of the tumour microbiome to interact with the host, thereby influencing host cell behaviour and cancer-associated processes. Further, we evaluate recent technological advances that allow us to actively quantify these populations and the relationships between cell types. Finally, we suggest how these dynamic interactions can be harnessed for therapeutic benefit in the treatment of cancer.}, }
@article {pmid35695645, year = {2021}, author = {Swafford, AD and Khandelwal, S and Bhute, S}, title = {Potential Immune-Microbiome Interactions in Breast Cancer May Advance Treatment: What's Holding Us Back?.}, journal = {Critical reviews in immunology}, volume = {41}, number = {6}, pages = {27-42}, doi = {10.1615/CritRevImmunol.2022043153}, pmid = {35695645}, issn = {1040-8401}, mesh = {*Breast Neoplasms/therapy ; Dysbiosis ; Female ; *Gastrointestinal Microbiome ; Humans ; Immunotherapy ; *Microbiota ; Tumor Microenvironment ; }, abstract = {The impact of the human microbiome, the diverse collection of microorganisms that inhabit nearly every niche in the human body, in shaping the immune response to dysbiotic events is apparent if poorly understood, particularly in complex, evolving disease states such as breast cancer. The impacts can be both indirect via metabolites and immune-interactions along the skin, gut, and oral cavities where the microbial communities are most abundant, or direct in the tumor microenvironment where microbial activities can promote growth or clearance of cancerous cells. Based on reports of using gut microbial signatures to predict therapeutic efficacy, the role that gut microbes and their metabolites may play in shaping the success or failure of immunotherapy has been extensively reviewed. In this review, we dissect the evidence for the direct and distal impact of microbes on oncogenesis, tumor growth and the immune responses to combat or promote tolerance of breast cancer tumors. Implementation of robust, valid analyses and methods are lacking in the field, and we provide recommendations for researchers and clinicians to work together to characterize the micro-biome-immune-breast cancer interactions that will hopefully enable the next generation of biomarkers and targets for improving disease outcomes.}, }
@article {pmid35695644, year = {2021}, author = {Maslinska, M and Kostyra-Grabczak, K and Królicki, L and Kwiatkowska, B}, title = {The Role of the Microbiome in Sjogren's Syndrome.}, journal = {Critical reviews in immunology}, volume = {41}, number = {6}, pages = {13-26}, doi = {10.1615/CritRevImmunol.2022043083}, pmid = {35695644}, issn = {1040-8401}, mesh = {Autoantigens ; *Autoimmune Diseases ; Dysbiosis ; Humans ; *Microbiota ; *Sjogren's Syndrome/diagnosis ; }, abstract = {The human microbiome is a living ecosystem existing within the host organism, determined by a balance between pathogenic microorganisms, symbionts, and commensals. The disturbance of microbiome composition-dysbiosis-often resulting in the excess of commensal numbers, may push the immune system towards activation of inflammatory and autoimmune processes. Changes in the microbiome of gut, eyes, and mouth may play a significant role in the development and course of autoimmune diseases, including primary Sjogren's syndrome. This autoimmune disease is associated with changes in the protective barrier of the epithelium, which is an important part of the antimicrobial defense. The development of pSS may be influenced by a mechanism of molecular mimicry between microbial antigens and self antigens leading to the initiation of anti-Ro60 antibody response. The knowledge of the influence of the state of microbiome on pSS may translate into the prophylaxis of the progression of dryness symptoms. The aim of this review is to present various aspects related to the human microbiome and Sjogren's syndrome.}, }
@article {pmid35695642, year = {2021}, author = {Passos, GA and Chaturvedi, VK}, title = {Preface Special Issue: Microbiome-Immune System Interactions.}, journal = {Critical reviews in immunology}, volume = {41}, number = {6}, pages = {v}, doi = {10.1615/CritRevImmunol.2022043499}, pmid = {35695642}, issn = {1040-8401}, mesh = {Autoimmunity ; *Gastrointestinal Microbiome ; Humans ; IgA Deficiency ; Immune System ; *Microbiota ; }, abstract = {Body homeostasis, immune response to microbial infections or vaccination, control of cancer onset or autoimmune or inflammatory diseases, as well as autism or other behavioral disorders, among other examples, are now recognized to be associated with the complex constitution of the body's microbiome. Recent findings demonstrate that the microbial composition, i.e., pathogenic, symbionts, and commensal viruses, bacteria, or yeast mainly in the gut, is strongly associated with susceptibility/resistance to several classes of diseases or its therapeutic response. This Special Issue focuses on the processes that link the human microbiome to three classes of diseases; immunodeficiency, autoimmunity, and cancer. Review articles cover aspects of the recent progress in selective immunoglobulin A (IgA) deficiency, Sjörgren's syndrome, breast cancer.}, }
@article {pmid35423066, year = {2020}, author = {Frateloreto, F and Capocasa, G and Olivo, G and Abdel Hady, K and Sappino, C and Di Berto Mancini, M and Levi Mortera, S and Lanzalunga, O and Di Stefano, S}, title = {Increasing the steric hindrance around the catalytic core of a self-assembled imine-based non-heme iron catalyst for C-H oxidation.}, journal = {RSC advances}, volume = {11}, number = {1}, pages = {537-542}, pmid = {35423066}, issn = {2046-2069}, abstract = {Sterically hindered imine-based non-heme complexes 4 and 5 rapidly self-assemble in acetonitrile at 25 °C, when the corresponding building blocks are added in solution in the proper ratios. Such complexes are investigated as catalysts for the H2O2 oxidation of a series of substrates in order to ascertain the role and the importance of the ligand steric hindrance on the action of the catalytic core 1, previously shown to be an efficient catalyst for aliphatic and aromatic C-H bond oxidation. The study reveals a modest dependence of the output of the oxidation reactions on the presence of bulky substituents in the backbone of the catalyst, both in terms of activity and selectivity. This result supports a previously hypothesized catalytic mechanism, which is based on the hemi-lability of the metal complex. In the active form of the catalyst, one of the pyridine arms temporarily leaves the iron centre, freeing up a lot of room for the access of the substrate.}, }
@article {pmid35846090, year = {2021}, author = {Ludwig, H and Hausmann, B and Schreder, M and Pönisch, W and Zojer, N and Knop, S and Gunsilius, E and Egle, A and Petzer, A and Einsele, H and Hajek, R and Weisel, K and Krenosz, KJ and Lang, A and Lechner, D and Greil, R and Berry, D}, title = {Reduced alpha diversity of the oral microbiome correlates with short progression-free survival in patients with relapsed/refractory multiple myeloma treated with ixazomib-based therapy (AGMT MM 1, phase II trial).}, journal = {EJHaem}, volume = {2}, number = {1}, pages = {99-103}, pmid = {35846090}, issn = {2688-6146}, abstract = {Alterations in the human microbiome have been linked to several malignant diseases. Here, we investigated the oral microbiome of 79 patients with relapsed/refractory multiple myeloma (MM) treated with ixazomib-thalidomide-dexamethasone. Increased alpha diversity (Shannon index) at the phylum level was associated with longer progression-free survival (PFS) (10.2 vs 8.5 months, P = .04), particularly in patients with very long (>75% quartile) PFS . Additionally, alpha diversity was lower in patients with progressive disease (P < .05). These findings suggest an interrelationship between the oral microbiome and outcome in patients with MM and encourage a novel direction for diagnostic and/or therapeutic strategies.}, }
@article {pmid34368751, year = {2020}, author = {Wang, XW and Liu, YY}, title = {Comparative study of classifiers for human microbiome data.}, journal = {Medicine in microecology}, volume = {4}, number = {}, pages = {}, pmid = {34368751}, issn = {2590-0978}, support = {U19 AI095219/AI/NIAID NIH HHS/United States ; U01 HL089856/HL/NHLBI NIH HHS/United States ; R01 AI141529/AI/NIAID NIH HHS/United States ; R01 HD093761/HD/NICHD NIH HHS/United States ; UH3 OD023268/OD/NIH HHS/United States ; }, abstract = {Accumulated evidence has shown that commensal microorganisms play key roles in human physiology and diseases. Dysbiosis of the human-associated microbial communities, often referred to as the human microbiome, has been associated with many diseases. Applying supervised classification analysis to the human microbiome data can help us identify subsets of microorganisms that are highly discriminative and hence build prediction models that can accurately classify unlabeled samples. Here, we systematically compare two state-of-the-art ensemble classifiers: Random Forests (RF), eXtreme Gradient Boosting decision trees (XGBoost) and two traditional methods: The elastic net (ENET) and Support Vector Machine (SVM) in the classification analysis of 29 benchmark human microbiome datasets. We find that XGBoost outperforms all other methods only in a few benchmark datasets. Overall, the XGBoost, RF and ENET display comparable performance in the remaining benchmark datasets. The training time of XGBoost is much longer than others, partially due to the much larger number of hyperparameters in XGBoost. We also find that the most important features selected by the four classifiers partially overlap. Yet, the difference between their classification performance is almost independent of this overlap.}, }
@article {pmid35117679, year = {2020}, author = {Mallika, L and Augustine, D and Rao, RS and Patil, S and Alamir, AWH and Awan, KH and Sowmya, SV and Haragannavar, VC and Prasad, K}, title = {Does microbiome shift play a role in carcinogenesis? A systematic review.}, journal = {Translational cancer research}, volume = {9}, number = {4}, pages = {3153-3166}, pmid = {35117679}, issn = {2219-6803}, abstract = {Recent scientific advances have presented substantial evidence that there is a multifaceted relationship between the microbiome and cancer. Humans are hosts to multifarious microbial communities, and these resident microbes contribute to both health and disease. Circulating toxic metabolites from these resident microbes may contribute to the development and progression of cancer. The aim of this systematic review was to evaluate microbiome and microbial shift contribution to the development and progression of cancer. This systematic review provides an analytical presentation of the evidence linking various parts of the microbiota to cancer. Searches were performed in databases such as PubMed, Google Scholar, Scopus, EBSCO, E-Journals and Science Direct from the time of their establishment until May 2018 with the following search terms: cancer or human microbe or cancer and human microbiome AND shift in microbes in cancer. The merged data were assessed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Cochrane's Risk of Bias Tool was used to assess the bias. Initially, 2,691 articles were identified, out of which 60 full-text articles were screened and re-evaluated. Among them, 14 were excluded based on inclusion/exclusion criteria; eventually, 46 articles were included in the systematic review. The reports of 46 articles revealed that microbial shift involving Candida species, Fusobacterium nucleatum, Porphyromonas gingivalis, Helicobacter pylori and Human papilloma virus (HPV) 16 &amp; 18 were most commonly involved in various human cancers. In particular, organisms, such as Candida albicans, Fusobacterium nucleatum, Porphyromonas gingivalis and HPV-16 were found to be more prevalent in oral cancer. The present systematic review emphasizes that the role and diverse contributions of the microbiome in carcinogenesis will provide opportunities for the development of effective diagnostic and preventive methods.}, }
@article {pmid35117578, year = {2020}, author = {Li, J and Chu, R and Wang, C and Li, Y and Wu, B and Wan, J}, title = {Microbiome characteristics and Bifidobacterium longum in colorectal cancer patients pre- and post-chemotherapy.}, journal = {Translational cancer research}, volume = {9}, number = {4}, pages = {2178-2190}, pmid = {35117578}, issn = {2219-6803}, abstract = {BACKGROUND: With the development of next generation sequencing technology, a lot of research has focused on the role of human microbiome in regulating immunity. The present study evaluated microbiome changes of colorectal cancer patients who received XELOX regimen (capecitabine plus oxaliplatin) without requiring antimicrobials.<br><br>METHODS: Stool samples from 7 patients (3 females/4 males) after screening of 11 patients before and after XELOX chemotherapy were subjected to 16S ribosomal RNA (rRNA) sequencing and flora dynamics compared at baseline and after 8 weeks of chemotherapy. Enrolled patients were newly diagnosed with stage IV colorectal cancer and had not received antimicrobial therapy or surgery. XELOX was administered for 2 cycles or 2-weekly treatments for 3 cycles.<br><br>RESULTS: The patterns of relative abundance of all bacteria isolated from stool samples before or after chemotherapy treatment appeared to be different, but there were no significant differences in the Kyoto Encyclopedia of Genes and Genomes (KEGG) metabolism pathway between the two groups. The top five pathways in patients were the two-component system, phenylalanine metabolism, degradation of aromatic compounds, beta-lactam resistance and folate biosynthesis. More than 99.6% intestinal flora isolates were bacteria, <0.4% were viruses and Archaea. The relative abundances of the 5 most common bacterial phyla in fecal samples before chemotherapy were Bacteroides, Firmicutes, Proteobacteria, Actinobacteria and Verrucomicrobia. The abundance of Actinomycetes in stools after chemotherapy was increased to 2.5 fold higher than before chemotherapy. Bifidobacterium longum species were significantly elevated in stools after chemotherapy (P<0.05), and changes of relative abundance of Bifidobacterium longum species after chemotherapy from baseline in favorable outcome population (stable disease) was significant higher than them in unfavorable outcome population (progressive disease, PD) (P=0.023).<br><br>CONCLUSIONS: The results indicated that Actinomyces in the gut might have a positive clinical outcome for colorectal cancer patients. This idea needs further studies to examine the actions of Actinomyces on inhibition of tumor growth.}, }
@article {pmid34278055, year = {2019}, author = {Di Guglielmo, MD and Franke, K and Cox, C and Crowgey, EL}, title = {Whole genome metagenomic analysis of the gut microbiome of differently fed infants identifies differences in microbial composition and functional genes, including an absent CRISPR/Cas9 gene in the formula-fed cohort.}, journal = {Human microbiome journal}, volume = {12}, number = {}, pages = {}, pmid = {34278055}, issn = {2452-2317}, support = {P20 GM103446/GM/NIGMS NIH HHS/United States ; P30 GM114736/GM/NIGMS NIH HHS/United States ; U54 GM104941/GM/NIGMS NIH HHS/United States ; }, abstract = {BACKGROUND: Advancements in sequencing capabilities have enhanced the study of the human microbiome. There are limited studies focused on the gastro-intestinal (gut) microbiome of infants, particularly the impact of diet between breast-fed (BF) versus formula-fed (FF). It is unclear what effect, if any, early feeding has on short-term or long-term composition and function of the gut microbiome.<br><br>RESULTS: Using a shotgun metagenomics approach, differences in the gut microbiome between BF (n = 10) and FF (n = 5) infants were detected. A Jaccard distance principle coordinate analysis was able to cluster BF versus FF infants based on the presence or absence of species identified in their gut microbiome. Thirty-two genera were identified as statistically different in the gut microbiome sequenced between BF and FF infants. Furthermore, the computational workflow identified 371 bacterial genes that were statistically different between the BF and FF cohorts in abundance. Only seven genes were lower in abundance (or absent) in the FF cohort compared to the BF cohort, including CRISPR/Cas9; whereas, the remaining candidates, including autotransporter adhesins, were higher in abundance in the FF cohort compared to BF cohort.<br><br>CONCLUSIONS: These studies demonstrated that FF infants have, at an early age, a significantly different gut microbiome with potential implications for function of the fecal microbiota. Interactions between the fecal microbiota and host hinted at here have been linked to numerous diseases. Determining whether these non-abundant or more abundant genes have biological consequence related to infant feeding may aid in understanding the adult gut microbiome, and the pathogenesis of obesity.}, }
@article {pmid34222889, year = {2019}, author = {Shahi, F and Redeker, K and Chong, J}, title = {Rethinking antimicrobial stewardship paradigms in the context of the gut microbiome.}, journal = {JAC-antimicrobial resistance}, volume = {1}, number = {1}, pages = {dlz015}, pmid = {34222889}, issn = {2632-1823}, abstract = {Ongoing concerns over the presence and persistence of antimicrobial resistance (AMR), particularly in Gram-negative bacteria, continue to have significant global health impacts. The gastrointestinal tract, or 'gut', environment amplifies AMR in the human gut microbiome, even in the absence of antibiotics. It constitutes a complex and diverse community of organisms, and patterns and alterations within it are increasingly being found to be associated with states of health and disease. Our understanding of the effects of routes of administration of antimicrobials on the gut microbiome is still lacking despite recent advances in metagenomics. In this article we review current evidence for antibiotic effects on gut microbiota and explore possible prescribing and stewardship approaches that would seek to minimize these effects. If we are to preserve existing and new antimicrobials, we need to consider their use in the context of their effect on gut ecology, and the human microbiome in general.}, }
@article {pmid34917757, year = {2019}, author = {Grenga, L and Pible, O and Armengaud, J}, title = {Pathogen proteotyping: A rapidly developing application of mass spectrometry to address clinical concerns.}, journal = {Clinical mass spectrometry (Del Mar, Calif.)}, volume = {14 Pt A}, number = {}, pages = {9-17}, pmid = {34917757}, issn = {2376-9998}, abstract = {For the rapid and reliable differentiation of clinically-relevant bacterial species, mass spectrometry-based methods have emerged in recent years as valid alternatives to existing techniques. Mass profiles generated by whole-cell Matrix-Assisted Laser Desorption Ionization-Time of Flight mass spectrometry have revolutionized microorganism identification and proven their potential for proteotyping at the species level. Indeed, the methodology has been widely deployed in clinical settings. However, the low resolution and dynamic range of the methodology has limited its capacity to distinguish between subspecies. This discrimination capacity is pivotal in cases where certain strains display virulence or antibiotic resistance, and for epidemiologic analyses. Moreover, sensitivity and specificity are both key parameters when attempting to discriminate between microorganisms present in complex multi-pathogenic samples. These two parameters are also essential to meet the growing interest in the characterization of microorganisms contained within even more complex samples, such as the human microbiome. Tandem mass spectrometry, with its high resolution, holds great potential for use in the real-time direct analysis of pathogens at the most relevant taxonomic rank in routine clinical practice. This review explores the numerous benefits and challenges of implementing advanced proteotyping methods, based on tandem mass spectrometry, in clinical laboratories. We provide an overview of the current applications and methodologies, while also discussing recent improvements and potential new approaches for typing, as well as their future applications.}, }
@article {pmid35415428, year = {2019}, author = {Chandrababu, S and Bastola, D}, title = {An Integrated Approach to Recognize Potential Protective Effects of Culinary Herbs Against Chronic Diseases.}, journal = {Journal of healthcare informatics research}, volume = {3}, number = {2}, pages = {184-199}, pmid = {35415428}, issn = {2509-4971}, abstract = {Secondary metabolites in plants have been of interest to humans for their wide variety of functions, including its use as dye, drugs, or perfumes. They are increasingly recognized as potential sources of new natural drugs and antibiotics. More recently, gut-associated microbes have been found to fulfill important functions in human health. However, our knowledge about the impact of secondary metabolites from culinary herbs on gut microbiome is limited. The present study was conducted to access the availability of computational resources relating to secondary metabolites and bioactive compounds in culinary herbs. A graph-based database HerbMicrobeDataBase (HMDB) was developed using Neo4j framework. It integrates knowledge from key biological entities associated in maintaining gut health and provides efficient storage/retrieval and graphical presentation of botanical, biochemical, and pharmacological data for culinary herbs and the human microbiome. We demonstrate the utility of this resource in understanding the molecular mechanism of metabolite production as well as their therapeutic or toxicological effects on gut microbes.}, }
@article {pmid36119463, year = {2015}, author = {Darling, KW and Boyce, AM and Cho, MK and Sankar, PL}, title = {"What is the FDA Going to Think?": Negotiating Values through Reflective and Strategic Category Work in Microbiome Science.}, journal = {Science, technology &amp; human values}, volume = {40}, number = {1}, pages = {71-95}, pmid = {36119463}, issn = {0162-2439}, support = {P50 HG003389/HG/NHGRI NIH HHS/United States ; R01 HG004900/HG/NHGRI NIH HHS/United States ; }, abstract = {The US National Institute of Health's Human Microbiome Project aims to use genomic techniques to understand the microbial communities that live on the human body. The emergent field of microbiome science brought together diverse disciplinary perspectives and technologies, thus facilitating the negotiation of differing values. Here, we describe how values are conceptualized and negotiated within microbiome research. Analyzing discussions from a series of interdisciplinary workshops conducted with microbiome researchers, we argue that negotiations of epistemic, social, and institutional values were inextricable from the reflective and strategic category work (i.e., the work of anticipating and strategizing around divergent sets of institutional categories) that defined and organized the microbiome as an object of study and a potential future site of biomedical intervention. Negotiating the divergence or tension between emerging scientific and regulatory classifications also activated "values levers" and opened up reflective discussions of how classifications embody values and how these values might differ across domains. These data suggest that scholars at the intersections of science and technology studies, ethics, and policy could leverage such openings to identify and intervene in the ways that ethical/regulatory and scientific/technical practices are coproduced within unfolding research.}, }
@article {pmid32742640, year = {2020}, author = {Wagner, J and Kancherla, J and Braccia, D and Matsumara, J and Felix, V and Crabtree, J and Mahurkar, A and Corrada Bravo, H}, title = {Interactive exploratory data analysis of Integrative Human Microbiome Project data using Metaviz.}, journal = {F1000Research}, volume = {9}, number = {}, pages = {601}, pmid = {32742640}, issn = {2046-1402}, support = {R01 GM114267/GM/NIGMS NIH HHS/United States ; U54 DK102556/DK/NIDDK NIH HHS/United States ; }, mesh = {*Data Analysis ; Data Interpretation, Statistical ; Humans ; *Microbiota ; Research Design ; }, abstract = {The rich data produced by the second phase of the Human Microbiome Project (iHMP) offers a unique opportunity to test hypotheses that interactions between microbial communities and a human host might impact an individual's health or disease status. In this work we describe infrastructure that integrates Metaviz, an interactive microbiome data analysis and visualization tool, with the iHMP Data Coordination Center web portal and the HMP2Data R/Bioconductor package. We describe integrative statistical and visual analyses of two datasets from iHMP using Metaviz along with the metagenomeSeq R/Bioconductor package for statistical analysis of differential abundance analysis. These use cases demonstrate the utility of a combined approach to access and analyze data from this resource.}, }
@article {pmid33816535, year = {2021}, author = {Stavropoulou, E and Kantartzi, K and Tsigalou, C and Aftzoglou, K and Voidarou, C and Konstantinidis, T and Chifiriuc, MC and Thodis, E and Bezirtzoglou, E}, title = {Microbiome, Immunosenescence, and Chronic Kidney Disease.}, journal = {Frontiers in medicine}, volume = {8}, number = {}, pages = {661203}, pmid = {33816535}, issn = {2296-858X}, abstract = {The gut microbiome is known as an important predictive tool for perceiving characteristic shifts in disease states. Multiple renal diseases and pathologies seem to be associated with gut dysbiosis which directly affects host homeostasis. The gastrointestinal-kidney dialogue confers interesting information about the pathogenesis of multiple kidney diseases. Moreover, aging is followed by specific shifts in the human microbiome, and gradual elimination of physiological functions predisposes the microbiome to inflammaging, sarcopenia, and disease. Aging is characterized by a microbiota with an abundance of disease-associated pathobionts. Multiple factors such as the immune system, environment, medication, diet, and genetic endowment are involved in determining the age of the microbiome in health and disease. Our present review promotes recently acquired knowledge and is expected to inspire researchers to advance studies and investigations on the involved pathways of the gut microbiota and kidney axis.}, }
@article {pmid33816334, year = {2021}, author = {Bostanci, N and Krog, MC and Hugerth, LW and Bashir, Z and Fransson, E and Boulund, F and Belibasakis, GN and Wannerberger, K and Engstrand, L and Nielsen, HS and Schuppe-Koistinen, I}, title = {Dysbiosis of the Human Oral Microbiome During the Menstrual Cycle and Vulnerability to the External Exposures of Smoking and Dietary Sugar.}, journal = {Frontiers in cellular and infection microbiology}, volume = {11}, number = {}, pages = {625229}, pmid = {33816334}, issn = {2235-2988}, mesh = {Dietary Sugars ; *Dysbiosis ; Female ; Humans ; Menstrual Cycle ; *Microbiota ; Smoking ; }, abstract = {Physiological hormonal fluctuations exert endogenous pressures on the structure and function of the human microbiome. As such, the menstrual cycle may selectively disrupt the homeostasis of the resident oral microbiome, thus compromising oral health. Hence, the aim of the present study was to structurally and functionally profile the salivary microbiome of 103 women in reproductive age with regular menstrual cycle, while evaluating the modifying influences of hormonal contraceptives, sex hormones, diet, and smoking. Whole saliva was sampled during the menstrual, follicular, and luteal phases (n = 309) of the cycle, and the participants reported questionnaire-based data concerning their life habits and oral or systemic health. No significant differences in alpha-diversity or phase-specific clustering of the overall microbiome were observed. Nevertheless, the salivary abundances of genera Campylobacter, Haemophilus, Prevotella, and Oribacterium varied throughout the cycle, and a higher species-richness was observed during the luteal phase. While the overall community structure maintained relatively intact, its functional properties were drastically affected. In particular, 11 functional modules were differentially abundant throughout the menstrual cycle, including pentose phosphate metabolism, and biosynthesis of cobalamin and neurotransmitter gamma-aminobutyric acid. The menstrual cycle phase, but not oral contraceptive usage, was accountable for greater variations in the metabolic pathways of the salivary microbiome. Further co-risk factor analysis demonstrated that Prevotella and Veillonella were increased in current smokers, whereas high dietary sugar consumption modified the richness and diversity of the microbiome during the cycle. This is the first large study to systematically address dysbiotic variations of the oral microbiome during the course of menstrual cycle, and document the additive effect of smoking and sugar consumption as environmental risk factors. It reveals the structural resilience and functional adaptability of the oral microbiome to the endogenous hormonal pressures of the menstrual cycle, while revealing its vulnerability to the exogenous exposures of diet and smoking.}, }
@article {pmid33806607, year = {2021}, author = {Callanan, J and Stockdale, SR and Shkoporov, A and Draper, LA and Ross, RP and Hill, C}, title = {Biases in Viral Metagenomics-Based Detection, Cataloguing and Quantification of Bacteriophage Genomes in Human Faeces, a Review.}, journal = {Microorganisms}, volume = {9}, number = {3}, pages = {}, pmid = {33806607}, issn = {2076-2607}, support = {12/RC/2273_P2/SFI_/Science Foundation Ireland/Ireland ; }, abstract = {The human gut is colonised by a vast array of microbes that include bacteria, viruses, fungi, and archaea. While interest in these microbial entities has largely focused on the bacterial constituents, recently the viral component has attracted more attention. Metagenomic advances, compared to classical isolation procedures, have greatly enhanced our understanding of the composition, diversity, and function of viruses in the human microbiome (virome). We highlight that viral extraction methodologies are crucial in terms of identifying and characterising communities of viruses infecting eukaryotes and bacteria. Different viral extraction protocols, including those used in some of the most significant human virome publications to date, have introduced biases affecting their a overall conclusions. It is important that protocol variations should be clearly highlighted across studies, with the ultimate goal of identifying and acknowledging biases associated with different protocols and, perhaps, the generation of an unbiased and standardised method for examining this portion of the human microbiome.}, }
@article {pmid33801755, year = {2021}, author = {Baldelli, V and Scaldaferri, F and Putignani, L and Del Chierico, F}, title = {The Role of Enterobacteriaceae in Gut Microbiota Dysbiosis in Inflammatory Bowel Diseases.}, journal = {Microorganisms}, volume = {9}, number = {4}, pages = {}, pmid = {33801755}, issn = {2076-2607}, abstract = {Inflammatory bowel diseases (IBDs) are a group of chronic gastrointestinal inflammatory diseases with unknown etiology. There is a combination of well documented factors in their pathogenesis, including intestinal microbiota dysbiosis. The symbiotic microbiota plays important functions in the host, and the loss of beneficial microbes could favor the expansion of microbial pathobionts. In particular, the bloom of potentially harmful Proteobacteria, especially Enterobacteriaceae, has been described as enhancing the inflammatory response, as observed in IBDs. Herein, we seek to investigate the contribution of Enterobacteriaceae to IBD pathogenesis whilst considering the continuous expansion of the literature and data. Despite the mechanism of their expansion still remaining unclear, their expansion could be correlated with the increase in nitrate and oxygen levels in the inflamed gut and with the bile acid dysmetabolism described in IBD patients. Furthermore, in several Enterobacteriaceae studies conducted at a species level, it has been suggested that some adherent-invasive Escherichia coli (AIEC) play an important role in IBD pathogenesis. Overall, this review highlights the pivotal role played by Enterobacteriaceae in gut dysbiosis associated with IBD pathogenesis and progression.}, }
@article {pmid33799784, year = {2021}, author = {Arsenijevic, T and Nicolle, R and Bouchart, C and D'Haene, N and Demetter, P and Puleo, F and Van Laethem, JL}, title = {Pancreatic Cancer Meets Human Microbiota: Close Encounters of the Third Kind.}, journal = {Cancers}, volume = {13}, number = {6}, pages = {}, pmid = {33799784}, issn = {2072-6694}, abstract = {Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal types of cancer with a dismal prognosis. The five-year survival rate has not changed significantly in over 40 years. Current first-line treatments only offer a modest increase in overall survival in unselected populations, and there is an urgent need to personalize treatment in this aggressive disease and develop new therapeutic strategies. Evolving evidence suggests that the human microbiome impacts cancerogenesis and cancer resistance to therapy. The mechanism of action and interaction of microbiome and PDAC is still under investigation. Direct and indirect effects have been proposed, and the use of several microbiome signatures as predictive and prognostic biomarkers for pancreatic cancer are opening new therapeutic horizons. In this review, we provide an overview for the clinicians of studies describing the influence and associations of oral, gastrointestinal and intratumoral microbiota on PDAC development, progression and resistance to therapy and the potential use of microbiota as a diagnostic, prognostic and predictive biomarker for PDAC.}, }
@article {pmid33798404, year = {2021}, author = {Ahn, J and Hayes, RB}, title = {Environmental Influences on the Human Microbiome and Implications for Noncommunicable Disease.}, journal = {Annual review of public health}, volume = {42}, number = {}, pages = {277-292}, pmid = {33798404}, issn = {1545-2093}, support = {P20 CA252728/CA/NCI NIH HHS/United States ; P30 CA008748/CA/NCI NIH HHS/United States ; R01 CA159036/CA/NCI NIH HHS/United States ; U01 CA250186/CA/NCI NIH HHS/United States ; }, mesh = {*Environment ; Global Health ; Humans ; *Microbiota ; Noncommunicable Diseases/*epidemiology ; Randomized Controlled Trials as Topic ; }, abstract = {The human microbiome contributes metabolic functions, protects against pathogens, educates the immune system, and through these basic functions, directly or indirectly, affects most of our physiologic functions. Here, we consider the human microbiome and its relationship to several major noncommunicable human conditions, including orodigestive tract cancers, neurologic diseases, diabetes, and obesity. We also highlight the scope of contextual macroenvironmental factors (toxicological and chemical environment, built environment, and socioeconomic environment) and individual microenvironmental factors (smoking, alcohol, and diet) that may push the microbiota toward less healthy or more healthy conditions, influencing the development of these diseases. Last, we highlight current uncertainties and challenges in the study of environmental influences on the human microbiome and implications for understanding noncommunicable disease, suggesting a research agenda to strengthen the scientific evidence base.}, }
@article {pmid33798253, year = {2021}, author = {Cho, JC}, title = {Human microbiome privacy risks associated with summary statistics.}, journal = {PloS one}, volume = {16}, number = {4}, pages = {e0249528}, pmid = {33798253}, issn = {1932-6203}, mesh = {*Computer Simulation ; Humans ; *Metagenomics ; *Microbiota ; *Privacy ; }, abstract = {Recognizing that microbial community composition within the human microbiome is associated with the physiological state of the host has sparked a large number of human microbiome association studies (HMAS). With the increasing size of publicly available HMAS data, the privacy risk is also increasing because HMAS metadata could contain sensitive private information. I demonstrate that a simple test statistic based on the taxonomic profiles of an individual's microbiome along with summary statistics of HMAS data can reveal the membership of the individual's microbiome in an HMAS sample. In particular, species-level taxonomic data obtained from small-scale HMAS can be highly vulnerable to privacy risk. Minimal guidelines for HMAS data privacy are suggested, and an assessment of HMAS privacy risk using the simulation method proposed is recommended at the time of study design.}, }
@article {pmid33796863, year = {2021}, author = {Townsend, EM and Kelly, L and Gannon, L and Muscatt, G and Dunstan, R and Michniewski, S and Sapkota, H and Kiljunen, SJ and Kolsi, A and Skurnik, M and Lithgow, T and Millard, AD and Jameson, E}, title = {Isolation and Characterization of Klebsiella Phages for Phage Therapy.}, journal = {PHAGE (New Rochelle, N.Y.)}, volume = {2}, number = {1}, pages = {26-42}, pmid = {33796863}, issn = {2641-6549}, support = {BB/M017982/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; MC_PC_17136/MRC_/Medical Research Council/United Kingdom ; MR/T030062/1/MRC_/Medical Research Council/United Kingdom ; }, abstract = {Introduction: Klebsiella is a clinically important pathogen causing a variety of antimicrobial resistant infections in both community and nosocomial settings, particularly pneumonia, urinary tract infection, and sepsis. Bacteriophage (phage) therapy is being considered a primary option for the treatment of drug-resistant infections of these types. Methods: We report the successful isolation and characterization of 30 novel, genetically diverse Klebsiella phages. Results: The isolated phages span six different phage families and nine genera, representing both lysogenic and lytic lifestyles. Individual Klebsiella phage isolates infected up to 11 of the 18 Klebsiella capsule types tested, and all 18 capsule-types were infected by at least one of the phages. Conclusions: Of the Klebsiella-infecting phages presented in this study, the lytic phages are most suitable for phage therapy, based on their broad host range, high virulence, short lysis period and given that they encode no known toxin or antimicrobial resistance genes. Phage isolates belonging to the Sugarlandvirus and Slopekvirus genera were deemed most suitable for phage therapy based on our characterization. Importantly, when applied alone, none of the characterized phages were able to suppress the growth of Klebsiella for more than 12 h, likely due to the inherent ease of Klebsiella to generate spontaneous phage-resistant mutants. This indicates that for successful phage therapy, a cocktail of multiple phages would be necessary to treat Klebsiella infections.}, }
@article {pmid33796850, year = {2021}, author = {Dhariwal, A and Junges, R and Chen, T and Petersen, FC}, title = {ResistoXplorer: a web-based tool for visual, statistical and exploratory data analysis of resistome data.}, journal = {NAR genomics and bioinformatics}, volume = {3}, number = {1}, pages = {lqab018}, pmid = {33796850}, issn = {2631-9268}, abstract = {The study of resistomes using whole metagenomic sequencing enables high-throughput identification of resistance genes in complex microbial communities, such as the human microbiome. Over recent years, sophisticated and diverse pipelines have been established to facilitate raw data processing and annotation. Despite the progress, there are no easy-to-use tools for comprehensive visual, statistical and functional analysis of resistome data. Thus, exploration of the resulting large complex datasets remains a key bottleneck requiring robust computational resources and technical expertise, which creates a significant hurdle for advancements in the field. Here, we introduce ResistoXplorer, a user-friendly tool that integrates recent advancements in statistics and visualization, coupled with extensive functional annotations and phenotype collection, to enable high-throughput analysis of common outputs generated from metagenomic resistome studies. ResistoXplorer contains three modules-the 'Antimicrobial Resistance Gene Table' module offers various options for composition profiling, functional profiling and comparative analysis of resistome data; the 'Integration' module supports integrative exploratory analysis of resistome and microbiome abundance profiles derived from metagenomic samples; finally, the 'Antimicrobial Resistance Gene List' module enables users to intuitively explore the associations between antimicrobial resistance genes and the microbial hosts using network visual analytics to gain biological insights. ResistoXplorer is publicly available at http://www.resistoxplorer.no.}, }
@article {pmid33796485, year = {2021}, author = {Ceprnja, M and Oros, D and Melvan, E and Svetlicic, E and Skrlin, J and Barisic, K and Starcevic, L and Zucko, J and Starcevic, A}, title = {Modeling of Urinary Microbiota Associated With Cystitis.}, journal = {Frontiers in cellular and infection microbiology}, volume = {11}, number = {}, pages = {643638}, pmid = {33796485}, issn = {2235-2988}, mesh = {*Cystitis ; Dysbiosis ; Female ; Humans ; *Microbiota ; *Urinary Tract Infections ; }, abstract = {A decade ago, when the Human Microbiome Project was starting, urinary tract (UT) was not included because the bladder and urine were considered to be sterile. Today, we are presented with evidence that healthy UT possesses native microbiota and any major event disrupting its "equilibrium" can impact the host also. This dysbiosis often leads to cystitis symptoms, which is the most frequent lower UT complaint, especially among women. Cystitis is one of the most common causes of antimicrobial drugs prescriptions in primary and secondary care and an important contributor to the problem of antimicrobial resistance. Despite this fact, we still have trouble distinguishing whether the primary cause of majority of cystitis cases is a single pathogen overgrowth, or a systemic disorder affecting entire UT microbiota. There are relatively few studies monitoring changes and dynamics of UT microbiota in cystitis patients, making this field of research still an unknown. In this study variations to the UT microbiota of cystitis patients were identified and microbial dynamics has been modeled. The microbial genetic profile of urine samples from 28 patients was analyzed by 16S rDNA Illumina sequencing and bioinformatics analysis. One patient with bacterial cystitis symptoms was prescribed therapy based on national guideline recommendations on antibacterial treatment of urinary tract infections (UTI) and UT microbiota change was monitored by 16S rDNA sequencing on 24 h basis during the entire therapy duration. The results of sequencing implied that a particular class of bacteria is associated with majority of cystitis cases in this study. The contributing role of this class of bacteria - Gammaproteobacteria, was further predicted by generalized Lotka-Volterra modeling (gLVM). Longitudinal microbiota insight obtained from a single patient under prescribed antimicrobial therapy revealed rapid and extensive changes in microbial composition and emphasized the need for current guidelines revision in regards to therapy duration. Models based on gLVM indicated protective role of two taxonomic classes of bacteria, Actinobacteria and Bacteroidia class, which appear to actively suppress pathogen overgrowth.}, }
@article {pmid33795545, year = {2021}, author = {Jalanka, J and Lam, C and Bennett, A and Hartikainen, A and Crispie, F and Finnegan, LA and Cotter, PD and Spiller, R}, title = {Colonic Gene Expression and Fecal Microbiota in Diarrhea-predominant Irritable Bowel Syndrome: Increased Toll-like Receptor 4 but Minimal Inflammation and no Response to Mesalazine.}, journal = {Journal of neurogastroenterology and motility}, volume = {27}, number = {2}, pages = {279-291}, pmid = {33795545}, issn = {2093-0879}, support = {MC_G1002464/MRC_/Medical Research Council/United Kingdom ; }, abstract = {BACKGROUND/AIMS: Diarrhea-predominant irritable bowel syndrome (IBS-D) has been previously associated with evidence of immune activation and altered microbiota. Our aim is to assess the effect of the anti-inflammatory agent, mesalazine, on inflammatory gene expression and microbiota composition in IBS-D.<br><br>METHODS: We studied a subset of patients (n = 43) from a previously published 12-week radomized placebo-controlled trial of mesalazine. Mucosal biopsies were assessed by immunohistochemistry and reverse transcription-polymerase chain reaction for a range of markers of inflammation, altered permeability, and sensory receptors including Toll-like receptors (TLRs) at randomization after treatment. All biopsy data were compared to 21 healthy controls. Patient's stool microbiota composition was analysed through 16S ribosomal RNA sequencing.<br><br>RESULTS: We found no evidence of increased immune activation compared to healthy controls. However, we did find increased expression of receptors in both sensory pathways and innate immune response including TLR4. Higher TLR4 expression was associated with greater urgency. TLR4 expression correlated strongly with the expression of the receptors bradykinin receptor B2, chemerin chemokine-like receptor 1, and transient receptor potential cation channel, subfamily A, member 1 as well as TLR4's downstream adaptor myeloid differentiation factor 88. Mesalazine had minimal effect on either gene expression or microbiota composition.<br><br>CONCLUSIONS: Biopsies from a well-characterized IBS-D cohort showed no substantial inflammation. Mesalazine has little effect on gene expression and its previous reported effect on fecal microbiota associated with much greater inflammation found in inflammatory bowel diseases is likely secondary to reduced inflammation. Increased expression of TLR4 and correlated receptors in IBS may mediate a general increase in sensitivity to external stimuli, particularly those that signal via the TLR system.}, }
@article {pmid33794144, year = {2021}, author = {Groussin, M and Poyet, M and Sistiaga, A and Kearney, SM and Moniz, K and Noel, M and Hooker, J and Gibbons, SM and Segurel, L and Froment, A and Mohamed, RS and Fezeu, A and Juimo, VA and Lafosse, S and Tabe, FE and Girard, C and Iqaluk, D and Nguyen, LTT and Shapiro, BJ and Lehtimäki, J and Ruokolainen, L and Kettunen, PP and Vatanen, T and Sigwazi, S and Mabulla, A and Domínguez-Rodrigo, M and Nartey, YA and Agyei-Nkansah, A and Duah, A and Awuku, YA and Valles, KA and Asibey, SO and Afihene, MY and Roberts, LR and Plymoth, A and Onyekwere, CA and Summons, RE and Xavier, RJ and Alm, EJ}, title = {Elevated rates of horizontal gene transfer in the industrialized human microbiome.}, journal = {Cell}, volume = {184}, number = {8}, pages = {2053-2067.e18}, doi = {10.1016/j.cell.2021.02.052}, pmid = {33794144}, issn = {1097-4172}, support = {TL1 TR002380/TR/NCATS NIH HHS/United States ; UL1 TR002377/TR/NCATS NIH HHS/United States ; }, mesh = {Bacteria/classification/*genetics/isolation &amp; purification ; DNA, Bacterial/chemistry/isolation &amp; purification/metabolism ; Feces/microbiology ; *Gastrointestinal Microbiome ; *Gene Transfer, Horizontal ; Genome, Bacterial ; Humans ; Phylogeny ; Rural Population ; Sequence Analysis, DNA ; Urban Population ; Whole Genome Sequencing ; }, abstract = {Industrialization has impacted the human gut ecosystem, resulting in altered microbiome composition and diversity. Whether bacterial genomes may also adapt to the industrialization of their host populations remains largely unexplored. Here, we investigate the extent to which the rates and targets of horizontal gene transfer (HGT) vary across thousands of bacterial strains from 15 human populations spanning a range of industrialization. We show that HGTs have accumulated in the microbiome over recent host generations and that HGT occurs at high frequency within individuals. Comparison across human populations reveals that industrialized lifestyles are associated with higher HGT rates and that the functions of HGTs are related to the level of host industrialization. Our results suggest that gut bacteria continuously acquire new functionality based on host lifestyle and that high rates of HGT may be a recent development in human history linked to industrialization.}, }
@article {pmid33792863, year = {2021}, author = {Bai, Y and Zhang, L and Lei, X}, title = {Human Endogenous Natural Products.}, journal = {Progress in the chemistry of organic natural products}, volume = {114}, number = {}, pages = {313-337}, pmid = {33792863}, issn = {2191-7043}, mesh = {Bile Acids and Salts ; *Biological Products ; Humans ; *Microbiota ; Tryptophan ; }, abstract = {Natural products are a class of chemical compounds that are biosynthesized by living organisms, including humans. Endogenous natural products are produced by human cells as well as by the human microbiome. This contribution describes the current understanding and recent progress made on endogenous natural products that are produced by human cells, including amines, steroids, and fatty acid-derived natural products. The co-metabolism and natural product produced by the human microbiome will also be described, including the involvement of tryptophan, bile acids, choline, and cysteine. New strategies and technologies have been introduced that can be applied to identify and characterize those natural products produced by the human microbiome in terms of their composition and physiological function.}, }
@article {pmid33788119, year = {2022}, author = {Johnson, SD and Fox, HS and Buch, S and Byrareddy, SN}, title = {Chronic Opioid Administration is Associated with Prevotella-dominated Dysbiosis in SIVmac251 Infected, cART-treated Macaques.}, journal = {Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology}, volume = {17}, number = {1-2}, pages = {3-14}, pmid = {33788119}, issn = {1557-1904}, support = {R01 DA043164/DA/NIDA NIH HHS/United States ; T32 NS105594/NS/NINDS NIH HHS/United States ; }, mesh = {Humans ; Animals ; Analgesics, Opioid/toxicity ; RNA, Ribosomal, 16S ; Macaca mulatta ; *Opioid-Related Disorders ; *HIV Infections ; }, abstract = {People living with the human immunodeficiency virus (HIV) have an elevated risk of opioid misuse due to both prescriptions for HIV-associated chronic pain and because injection drug use remains a primary mode of HIV transmission. HIV pathogenesis is characterized by chronic immune activation and microbial dysbiosis, and translocation across the gut barrier exacerbating inflammation. Despite the high rate of co-occurrence, little is known about the microbiome during chronic opioid use in the context of HIV and combination antiretroviral therapy (cART). We recently demonstrated the reduction of the CD4 + T-cell reservoir in lymphoid tissues but increased in microglia/macrophage reservoirs in CNS by using morphine-treated, simian immunodeficiency virus (SIV)-infected rhesus macaques with viremia suppressed by cART. To understand whether morphine may perturb the gut-brain axis, fecal samples were collected at necropsy, DNA isolated, and 16S rRNA sequenced and changes of the microbiome analyzed. We found that morphine treatment led to dysbiosis, primarily characterized by expansion of Bacteroidetes, particularly Prevotellaceae, at the expense of Firmicutes and other members of healthy microbial communities resulting in a lower α-diversity. Of the many genera in Prevotellaceae, the differences between the saline and morphine group were primarily due to a higher relative abundance of Prevotella_9, the taxa most similar to Prevotella copri, an inflammatory pathobiont in the human microbiome. These findings reinforce previous research showing that opioid abuse is associated with dysbiosis, therefore, warranting additional future research to elucidate the complex interaction between the host and opioid abuse during HIV and SIV infection.}, }
@article {pmid33786001, year = {2021}, author = {Sehli, S and Allali, I and Chahboune, R and Bakri, Y and Al Idrissi, N and Hamdi, S and Nejjari, C and Amzazi, S and Ghazal, H}, title = {Metagenomics Approaches to Investigate the Gut Microbiome of COVID-19 Patients.}, journal = {Bioinformatics and biology insights}, volume = {15}, number = {}, pages = {1177932221999428}, pmid = {33786001}, issn = {1177-9322}, abstract = {Over the last decade, it has become increasingly apparent that the microbiome is a central component in human well-being and illness. However, to establish innovative therapeutic methods, it is crucial to learn more about the microbiota. Thereby, the area of metagenomics and associated bioinformatics methods and tools has become considerable in the study of the human microbiome biodiversity. The application of these metagenomics approaches to studying the gut microbiome in COVID-19 patients could be one of the promising areas of research in the fight against the SARS-CoV-2 infection and disparity. Therefore, understanding how the gut microbiome is affected by or could affect the SARS-CoV-2 is very important. Herein, we present an overview of approaches and methods used in the current published studies on COVID-19 patients and the gut microbiome. The accuracy of these researches depends on the appropriate choice and the optimal use of the metagenomics bioinformatics platforms and tools. Interestingly, most studies reported that COVID-19 patients' microbiota are enriched with opportunistic microorganisms. The choice and use of appropriate computational tools and techniques to accurately investigate the gut microbiota is therefore critical in determining the appropriate microbiome profile for diagnosis and the most reliable antiviral or preventive microbial composition.}, }
@article {pmid33785319, year = {2021}, author = {Bui, TPN and de Vos, WM}, title = {Next-generation therapeutic bacteria for treatment of obesity, diabetes, and other endocrine diseases.}, journal = {Best practice &amp; research. Clinical endocrinology &amp; metabolism}, volume = {35}, number = {3}, pages = {101504}, doi = {10.1016/j.beem.2021.101504}, pmid = {33785319}, issn = {1878-1594}, mesh = {Bacteria ; *Diabetes Mellitus/therapy ; Diet ; *Gastrointestinal Microbiome ; Humans ; Obesity/therapy ; }, abstract = {The human gut microbiota has appeared as an important factor affecting host health and intestinal bacteria have recently emerged as potential therapeutics to treat diabetes and other endocrine diseases. These mainly anaerobic bacteria have been identified either via comparative "omics" analysis of the intestinal microbiota in healthy and diseased subjects or of data collected by fecal microbiota transplantation studies. Both approaches require advanced and in-depth sequencing technologies to perform massive genomic screening to select bacteria with potential benefits. It has been shown that these potentially therapeutic bacteria can either produce bioactive products that directly influence the host patho-physiology and endocrine systems or produce specific signaling molecules that may do so. These bioactive compounds can be formed via degradation of dietary or host-derived components or the conversion of intermediate compounds produced by fermentation of intestinal bacteria. Several of these bacteria have shown causality in preclinical models and entered clinical phase studies, while their mode of action is being analyzed. In this review, we summarize the research on the most promising bacterial candidates with therapeutic properties with a specific focus on diabetes.}, }
@article {pmid33785070, year = {2021}, author = {Wirbel, J and Zych, K and Essex, M and Karcher, N and Kartal, E and Salazar, G and Bork, P and Sunagawa, S and Zeller, G}, title = {Microbiome meta-analysis and cross-disease comparison enabled by the SIAMCAT machine learning toolbox.}, journal = {Genome biology}, volume = {22}, number = {1}, pages = {93}, pmid = {33785070}, issn = {1474-760X}, mesh = {Computational Biology/*methods ; Confounding Factors, Epidemiologic ; Crohn Disease/etiology ; Databases, Genetic ; Gastrointestinal Microbiome ; Humans ; *Machine Learning ; Meta-Analysis as Topic ; *Metagenome ; Metagenomics/*methods ; *Microbiota ; Models, Statistical ; ROC Curve ; *Software ; Workflow ; }, abstract = {The human microbiome is increasingly mined for diagnostic and therapeutic biomarkers using machine learning (ML). However, metagenomics-specific software is scarce, and overoptimistic evaluation and limited cross-study generalization are prevailing issues. To address these, we developed SIAMCAT, a versatile R toolbox for ML-based comparative metagenomics. We demonstrate its capabilities in a meta-analysis of fecal metagenomic studies (10,803 samples). When naively transferred across studies, ML models lost accuracy and disease specificity, which could however be resolved by a novel training set augmentation strategy. This reveals some biomarkers to be disease-specific, with others shared across multiple conditions. SIAMCAT is freely available from siamcat.embl.de .}, }
@article {pmid33783596, year = {2021}, author = {Zhao, H}, title = {The human microbiome and genetic disease: towards the integration of metagenomic and multi-omics data.}, journal = {Human genetics}, volume = {140}, number = {5}, pages = {701-702}, pmid = {33783596}, issn = {1432-1203}, mesh = {Data Analysis ; Genetic Diseases, Inborn/*microbiology ; Humans ; Metagenomics ; *Microbiota ; }, }
@article {pmid33777849, year = {2021}, author = {Gazzaniga, FS and Camacho, DM and Wu, M and Silva Palazzo, MF and Dinis, ALM and Grafton, FN and Cartwright, MJ and Super, M and Kasper, DL and Ingber, DE}, title = {Harnessing Colon Chip Technology to Identify Commensal Bacteria That Promote Host Tolerance to Infection.}, journal = {Frontiers in cellular and infection microbiology}, volume = {11}, number = {}, pages = {638014}, pmid = {33777849}, issn = {2235-2988}, mesh = {Animals ; Bacteria ; *Colon ; Intestinal Mucosa ; Mice ; *Symbiosis ; Technology ; }, abstract = {Commensal bacteria within the gut microbiome contribute to development of host tolerance to infection, however, identifying specific microbes responsible for this response is difficult. Here we describe methods for developing microfluidic organ-on-a-chip models of small and large intestine lined with epithelial cells isolated from duodenal, jejunal, ileal, or colon organoids derived from wild type or transgenic mice. To focus on host-microbiome interactions, we carried out studies with the mouse Colon Chip and demonstrated that it can support co-culture with living gut microbiome and enable assessment of effects on epithelial adhesion, tight junctions, barrier function, mucus production, and cytokine release. Moreover, infection of the Colon Chips with the pathogenic bacterium, Salmonella typhimurium, resulted in epithelial detachment, decreased tight junction staining, and increased release of chemokines (CXCL1, CXCL2, and CCL20) that closely mimicked changes previously seen in mice. Symbiosis between microbiome bacteria and the intestinal epithelium was also recapitulated by populating Colon Chips with complex living mouse or human microbiome. By taking advantage of differences in the composition between complex microbiome samples cultured on each chip using 16s sequencing, we were able to identify Enterococcus faecium as a positive contributor to host tolerance, confirming past findings obtained in mouse experiments. Thus, mouse Intestine Chips may represent new experimental in vitro platforms for identifying particular bacterial strains that modulate host response to pathogens, as well as for investigating the cellular and molecular basis of host-microbe interactions.}, }
@article {pmid33770448, year = {2021}, author = {Shine, EE and Crawford, JM}, title = {Molecules from the Microbiome.}, journal = {Annual review of biochemistry}, volume = {90}, number = {}, pages = {789-815}, doi = {10.1146/annurev-biochem-080320-115307}, pmid = {33770448}, issn = {1545-4509}, support = {R01 CA215553/CA/NCI NIH HHS/United States ; }, mesh = {Gastrointestinal Microbiome/genetics/physiology ; Humans ; Metagenomics/*methods ; Microbiota/genetics/*physiology ; Peptides/*metabolism ; Phenotype ; Polyketides/*metabolism ; }, abstract = {The human microbiome encodes a second genome that dwarfs the genetic capacity of the host. Microbiota-derived small molecules can directly target human cells and their receptors or indirectly modulate host responses through functional interactions with other microbes in their ecological niche. Their biochemical complexity has profound implications for nutrition, immune system development, disease progression, and drug metabolism, as well as the variation in these processes that exists between individuals. While the species composition of the human microbiome has been deeply explored, detailed mechanistic studies linking specific microbial molecules to host phenotypes are still nascent. In this review, we discuss challenges in decoding these interaction networks, which require interdisciplinary approaches that combine chemical biology, microbiology, immunology, genetics, analytical chemistry, bioinformatics, and synthetic biology. We highlight important classes of microbiota-derived small molecules and notable examples. An understanding of these molecular mechanisms is central to realizing the potential of precision microbiome editing in health, disease, and therapeutic responses.}, }
@article {pmid33763385, year = {2021}, author = {Jian, C and Salonen, A and Korpela, K}, title = {Commentary: How to Count Our Microbes? The Effect of Different Quantitative Microbiome Profiling Approaches.}, journal = {Frontiers in cellular and infection microbiology}, volume = {11}, number = {}, pages = {627910}, pmid = {33763385}, issn = {2235-2988}, mesh = {*Microbiota ; RNA, Ribosomal, 16S ; }, }
@article {pmid33762022, year = {2021}, author = {Malka, O and Kalson, D and Yaniv, K and Shafir, R and Rajendran, M and Ben-David, O and Kushmaro, A and Meijler, MM and Jelinek, R}, title = {Cross-kingdom inhibition of bacterial virulence and communication by probiotic yeast metabolites.}, journal = {Microbiome}, volume = {9}, number = {1}, pages = {70}, pmid = {33762022}, issn = {2049-2618}, mesh = {Bacterial Proteins/genetics ; Biofilms ; Communication ; Gene Expression Regulation, Bacterial ; Humans ; Kluyveromyces ; *Probiotics ; Virulence ; }, abstract = {BACKGROUND: Probiotic milk-fermented microorganism mixtures (e.g., yogurt, kefir) are perceived as contributing to human health, and possibly capable of protecting against bacterial infections. Co-existence of probiotic microorganisms are likely maintained via complex biomolecular mechanisms, secreted metabolites mediating cell-cell communication, and other yet-unknown biochemical pathways. In particular, deciphering molecular mechanisms by which probiotic microorganisms inhibit proliferation of pathogenic bacteria would be highly important for understanding both the potential benefits of probiotic foods as well as maintenance of healthy gut microbiome.<br><br>RESULTS: The microbiome of a unique milk-fermented microorganism mixture was determined, revealing a predominance of the fungus Kluyveromyces marxianus. We further identified a new fungus-secreted metabolite-tryptophol acetate-which inhibits bacterial communication and virulence. We discovered that tryptophol acetate blocks quorum sensing (QS) of several Gram-negative bacteria, particularly Vibrio cholerae, a prominent gut pathogen. Notably, this is the first report of tryptophol acetate production by a yeast and role of the molecule as a signaling agent. Furthermore, mechanisms underscoring the anti-QS and anti-virulence activities of tryptophol acetate were elucidated, specifically down- or upregulation of distinct genes associated with V. cholerae QS and virulence pathways.<br><br>CONCLUSIONS: This study illuminates a yet-unrecognized mechanism for cross-kingdom inhibition of pathogenic bacteria cell-cell communication in a probiotic microorganism mixture. A newly identified fungus-secreted molecule-tryptophol acetate-was shown to disrupt quorum sensing pathways of the human gut pathogen V. cholerae. Cross-kingdom interference in quorum sensing may play important roles in enabling microorganism co-existence in multi-population environments, such as probiotic foods and the gut microbiome. This discovery may account for anti-virulence properties of the human microbiome and could aid elucidating health benefits of probiotic products against bacterially associated diseases. Video Abstract.}, }
@article {pmid33757553, year = {2021}, author = {Santiago, M and Olesen, SW}, title = {16S rRNA sequencing of samples from universal stool bank donors.}, journal = {BMC research notes}, volume = {14}, number = {1}, pages = {108}, pmid = {33757553}, issn = {1756-0500}, mesh = {*Clostridium Infections ; *Fecal Microbiota Transplantation ; Feces ; Humans ; RNA, Ribosomal, 16S/genetics ; Tissue Donors ; }, abstract = {OBJECTIVES: Universal stool banks provide stool to physicians for use in treating recurrent Clostridioides difficile infection via fecal microbiota transplantation. Stool donors providing the material are rigorously screened for diseases and disorders with a potential microbiome etiology, and they are likely healthier than the controls in most microbiome datasets. 16S rRNA sequencing was performed on samples from a selection of stool donors at a large stool bank, OpenBiome, to characterize their gut microbial community and to compare samples across different timepoints and sequencing runs.<br><br>DATA DESCRIPTION: 16S rRNA sequencing was performed on 200 samples derived from 170 unique stool donations from 86 unique donors. Samples were sequenced on 11 different sequencing runs. We are making this data available because rigorously screened, likely very healthy stool donors may be useful for characterizing and understanding microbial community differences across different populations and will help shed light into the how the microbiome community promotes health and disease.}, }
@article {pmid33754165, year = {2021}, author = {Del Chierico, F and Manco, M and Gardini, S and Guarrasi, V and Russo, A and Bianchi, M and Tortosa, V and Quagliariello, A and Shashaj, B and Fintini, D and Putignani, L}, title = {Fecal microbiota signatures of insulin resistance, inflammation, and metabolic syndrome in youth with obesity: a pilot study.}, journal = {Acta diabetologica}, volume = {58}, number = {8}, pages = {1009-1022}, pmid = {33754165}, issn = {1432-5233}, support = {600932//European Commission (FP7 Information Communication Technologies Programme)/ ; }, mesh = {Adolescent ; Bacteria/classification/genetics ; Biomarkers/blood ; Child ; Feces/*microbiology ; Female ; Glucose Intolerance/microbiology ; Humans ; Hypertension/microbiology ; Inflammation/*microbiology ; Insulin Resistance/*physiology ; Male ; Metabolic Syndrome/*microbiology ; Metagenomics ; Microbiota/*physiology ; *Obesity/complications ; Pilot Projects ; RNA, Ribosomal, 16S/analysis ; Risk Factors ; Triglycerides/blood ; }, abstract = {AIMS: To identify fecal microbiota profiles associated with metabolic abnormalities belonging to the metabolic syndrome (MS), high count of white blood cells (WBCs) and insulin resistance (IR).<br><br>METHODS: Sixty-eight young patients with obesity were stratified for percentile distribution of MS abnormalities. A MS risk score was defined as low, medium, and high MS risk. High WBCs were defined as a count&#x2009;&#x2265;&#x2009;7.0 10[3]/&#xb5;L; severe obesity as body mass index Z-score&#x2009;&#x2265;&#x2009;2 standard deviations; IR as homeostatic assessment model algorithm of IR (HOMA)&#x2009;&#x2265;&#x2009;3.7. Stool samples were analyzed by 16S rRNA-based metagenomics.<br><br>RESULTS: We found reduced bacterial richness of fecal microbiota in patients with IR and high diastolic blood pressure (BP). Distinct microbial markers were associated to high BP (Clostridium and Clostridiaceae), low high-density lipoprotein cholesterol (Lachnospiraceae, Gemellaceae, Turicibacter), and high MS risk (Coriobacteriaceae), WBCs (Bacteroides caccae, Gemellaceae), severe obesity (Lachnospiraceae), and impaired glucose tolerance (Bacteroides ovatus and Enterobacteriaceae). Conversely, taxa such as Faecalibacterium prausnitzii, Parabacterodes, Bacteroides caccae, Oscillospira, Parabacterodes distasonis, Coprococcus, and Haemophilus parainfluenzae were associated to low MS risk score, triglycerides, fasting glucose and HOMA-IR, respectively. Supervised multilevel analysis grouped clearly "variable" patients based on the MS risk.<br><br>CONCLUSIONS: This was a proof-of-concept study opening the way at the identification of fecal microbiota signatures, precisely associated with cardiometabolic risk factors in young patients with obesity. These evidences led us to infer, while some gut bacteria have a detrimental role in exacerbating metabolic risk factors some others are beneficial ameliorating cardiovascular host health.}, }
@article {pmid33752405, year = {2021}, author = {Tužil, Jan and Filková, Barbora and Malina, Ji&#x159;&#xed; and Kerestes, Jan and Doležal, Tom&#xe1;&#x161;}, title = {Smoking in women with chronic vaginal discomfort is not associated with decreased abundance of Lactobacillus spp. but promotes Mobiluncus and Gardnerella spp. overgrowth - secondary analysis of trial data including microbio-me analysis.}, journal = {Ceska gynekologie}, volume = {86}, number = {1}, pages = {22-29}, doi = {10.48095/cccg202122}, pmid = {33752405}, issn = {1210-7832}, mesh = {Cross-Sectional Studies ; Female ; Gardnerella ; Gardnerella vaginalis ; Humans ; *Lactobacillus ; *Mobiluncus ; Randomized Controlled Trials as Topic ; Smoking/adverse effects ; Vagina ; }, abstract = {BACKGROUND: Smoking is considered a risk factor for bacterial vaginosis. It is currently unknown which parameters of the vaginal environment are affected and how smoking triggers the disease.<br><br>AIM OF THE STUDY: The primary objective is to estimate the effect size of smoking on vaginal pH and the Nugent score in patients with chronic vulvovaginal discomfort prior to the development of episode of vaginosis. The secondary goal is to investigate the effect of smoking on individual microscopic parameters of the vaginal environment and on subjectively reported symptoms of vaginal discomfort.<br><br>METHODS: Smoking reported by patients was tested as a predictor, using multivariate logistic and ordinal logistic regression analysis on a dataset from the first visit of a randomized trial NCT04171947, which enrolled patients with intermediate vaginal environment. We tested the primary hypothesis (odds ratio (OR) for vaginal pH > 4.5 and Nugent score > 3 in smokers) at the significance level &#xe1; = 5%. For exploratory analyses of the effect of smoking on the parameters of the vaginal environment, &#xe1; was corrected as per Bonferoni.<br><br>RESULTS: In a cross-sectional sample of 250 women after adjusting for other risk factors, smoking had an impact on the Nugent score (OR = 3.3 (1.3-8.5), P = 0.011), while pH was not affected (OR = 1.2 (0.5-2.8), P = 0.698). Smoking was associated with the prevalence of clue cells (P < 0.000), Gardnerella spp. (P = 0.001) and Mobiluncus spp. (P = 0.001), while the prevalence of Lactobacillus remained unchanged (P = 0.049).<br><br>CONCLUSION: Contrarily to common assumptions, vaginal Lactobacillus is not directly affected by smoking, which rather promotes the growth of bacteria of Gardnerella and Mobiluncus spp. Given that other parameters remained unaffected, it appears that smoking leads to vaginal dysbio-sis by creating specific favourable conditions for these two opportunistic&#xa0; pathogens.}, }
@article {pmid33738265, year = {2021}, author = {Ma, Y and Zhang, Y and Xiang, J and Xiang, S and Zhao, Y and Xiao, M and Du, F and Ji, H and Kaboli, PJ and Wu, X and Li, M and Wen, Q and Shen, J and Yang, Z and Li, J and Xiao, Z}, title = {Metagenome Analysis of Intestinal Bacteria in Healthy People, Patients With Inflammatory Bowel Disease and Colorectal Cancer.}, journal = {Frontiers in cellular and infection microbiology}, volume = {11}, number = {}, pages = {599734}, pmid = {33738265}, issn = {2235-2988}, mesh = {Bacteria/genetics ; *Colorectal Neoplasms ; Humans ; *Inflammatory Bowel Diseases ; Metagenome ; Metagenomics ; RNA, Ribosomal, 16S/genetics ; }, abstract = {OBJECTIVES: Several reports suggesting that the intestinal microbiome plays a key role in the development of inflammatory bowel disease (IBD) or colorectal cancer (CRC), but the changes of intestinal bacteria in healthy people, patients with IBD and CRC are not fully explained. The study aimed to investigate changes of intestinal bacteria in healthy subjects, patients with IBD, and patients with CRC.<br><br>MATERIALS: We collected data from the European Nucleotide Archive on healthy people and patients with colorectal cancer with the study accession number PRJEB6070, PRJEB7774, PRJEB27928, PRJEB12449, and PRJEB10878, collected IBD patient data from the Integrated Human Microbiome Project from the Human Microbiome Project Data Portal. We performed metagenome-wide association studies on the fecal samples from 290 healthy subjects, 512 IBD patients, and 285 CRC patients. We used the metagenomics dataset to study bacterial community structure, relative abundance, functional prediction, differentially abundant bacteria, and co-occurrence networks.<br><br>RESULTS: The bacterial community structure in both IBD and CRC was significantly different from healthy subjects. Our results showed that IBD patients had low intestinal bacterial diversity and CRC patients had high intestinal bacterial diversity compared to healthy subjects. At the phylum level, the relative abundance of Firmicutes in IBD decreased significantly, while the relative abundance of Bacteroidetes increased significantly. At the genus level, the relative abundance of Bacteroides in IBD was higher than in healthy people and CRC. Compared with healthy people and CRC, the main difference of intestinal bacteria in IBD patients was Bacteroidetes, and compared with healthy people and IBD, the main difference of intestinal bacteria in CRC patients was in Fusobacteria, Verrucomicrobia, and Proteobacteria. The main differences in the functional composition of intestinal bacteria in healthy people, IBD and CRC patients were L-homoserine and L-methionine biosynthesis, 5-aminoimidazole ribonucleotide biosynthesis II, L-methionine biosynthesis I, and superpathway of L-lysine, L-threonine, and L-methionine biosynthesis I. The results of stratified showed that the abundance of Firmicutes, Bacteroidetes, and Actinobacteria involved in metabolic pathways has significantly changed. Besides, the association network of intestinal bacteria in healthy people, IBD, and CRC patients has also changed.<br><br>CONCLUSIONS: In conclusion, compared with healthy people, the taxonomic and functional composition of intestinal bacteria in IBD and CRC patients was significantly changed.}, }
@article {pmid33737920, year = {2021}, author = {Marcos-Zambrano, LJ and Karaduzovic-Hadziabdic, K and Loncar Turukalo, T and Przymus, P and Trajkovik, V and Aasmets, O and Berland, M and Gruca, A and Hasic, J and Hron, K and Klammsteiner, T and Kolev, M and Lahti, L and Lopes, MB and Moreno, V and Naskinova, I and Org, E and Paciência, I and Papoutsoglou, G and Shigdel, R and Stres, B and Vilne, B and Yousef, M and Zdravevski, E and Tsamardinos, I and Carrillo de Santa Pau, E and Claesson, MJ and Moreno-Indias, I and Truu, J}, title = {Applications of Machine Learning in Human Microbiome Studies: A Review on Feature Selection, Biomarker Identification, Disease Prediction and Treatment.}, journal = {Frontiers in microbiology}, volume = {12}, number = {}, pages = {634511}, pmid = {33737920}, issn = {1664-302X}, abstract = {The number of microbiome-related studies has notably increased the availability of data on human microbiome composition and function. These studies provide the essential material to deeply explore host-microbiome associations and their relation to the development and progression of various complex diseases. Improved data-analytical tools are needed to exploit all information from these biological datasets, taking into account the peculiarities of microbiome data, i.e., compositional, heterogeneous and sparse nature of these datasets. The possibility of predicting host-phenotypes based on taxonomy-informed feature selection to establish an association between microbiome and predict disease states is beneficial for personalized medicine. In this regard, machine learning (ML) provides new insights into the development of models that can be used to predict outputs, such as classification and prediction in microbiology, infer host phenotypes to predict diseases and use microbial communities to stratify patients by their characterization of state-specific microbial signatures. Here we review the state-of-the-art ML methods and respective software applied in human microbiome studies, performed as part of the COST Action ML4Microbiome activities. This scoping review focuses on the application of ML in microbiome studies related to association and clinical use for diagnostics, prognostics, and therapeutics. Although the data presented here is more related to the bacterial community, many algorithms could be applied in general, regardless of the feature type. This literature and software review covering this broad topic is aligned with the scoping review methodology. The manual identification of data sources has been complemented with: (1) automated publication search through digital libraries of the three major publishers using natural language processing (NLP) Toolkit, and (2) an automated identification of relevant software repositories on GitHub and ranking of the related research papers relying on learning to rank approach.}, }
@article {pmid33737370, year = {2021}, author = {Mulkerrins, KB and Lyons, C and Shiaris, MP}, title = {Draft Genome Sequence of Enterococcus faecalis AS003, a Strain Possessing All Three Type II-a CRISPR Loci.}, journal = {Microbiology resource announcements}, volume = {10}, number = {11}, pages = {}, pmid = {33737370}, issn = {2576-098X}, abstract = {Enterococcus faecalis is a clinically significant member of the human microbiome. Three CRISPR-Cas loci are located in conserved locations. Previous studies provide evidence that E. faecalis strains with functional CRISPR-Cas genes are negatively correlated with antibiotic resistance. Here, we report the genome sequence of an unusual strain possessing all three CRISPR-Cas loci.}, }
@article {pmid33734582, year = {2021}, author = {Zimmermann, M and Patil, KR and Typas, A and Maier, L}, title = {Towards a mechanistic understanding of reciprocal drug-microbiome interactions.}, journal = {Molecular systems biology}, volume = {17}, number = {3}, pages = {e10116}, pmid = {33734582}, issn = {1744-4292}, support = {MC_UU_00025/11/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Animals ; Bacteria/metabolism ; Disease Models, Animal ; *Drug Interactions ; Host-Pathogen Interactions ; Humans ; Metagenomics ; *Microbiota ; Systems Biology ; }, abstract = {Broad-spectrum antibiotics target multiple gram-positive and gram-negative bacteria, and can collaterally damage the gut microbiota. Yet, our knowledge of the extent of damage, the antibiotic activity spectra, and the resistance mechanisms of gut microbes is sparse. This limits our ability to mitigate microbiome-facilitated spread of antibiotic resistance. In addition to antibiotics, non-antibiotic drugs affect the human microbiome, as shown by metagenomics as well as in vitro studies. Microbiome-drug interactions are bidirectional, as microbes can also modulate drugs. Chemical modifications of antibiotics mostly function as antimicrobial resistance mechanisms, while metabolism of non-antibiotics can also change the drugs' pharmacodynamic, pharmacokinetic, and toxic properties. Recent studies have started to unravel the extensive capacity of gut microbes to metabolize drugs, the mechanisms, and the relevance of such events for drug treatment. These findings raise the question whether and to which degree these reciprocal drug-microbiome interactions will differ across individuals, and how to take them into account in drug discovery and precision medicine. This review describes recent developments in the field and discusses future study areas that will benefit from systems biology approaches to better understand the mechanistic role of the human gut microbiota in drug actions.}, }
@article {pmid33724419, year = {2021}, author = {Rosiana, S and Zhang, L and Kim, GH and Revtovich, AV and Uthayakumar, D and Sukumaran, A and Geddes-McAlister, J and Kirienko, NV and Shapiro, RS}, title = {Comprehensive genetic analysis of adhesin proteins and their role in virulence of Candida albicans.}, journal = {Genetics}, volume = {217}, number = {2}, pages = {}, pmid = {33724419}, issn = {1943-2631}, support = {//CIHR/Canada ; }, mesh = {Animals ; Biofilms ; Caenorhabditis elegans/microbiology ; Candida albicans/*genetics/pathogenicity/physiology ; Cell Adhesion Molecules/*genetics/metabolism ; Cloning, Molecular ; Fungal Proteins/*genetics/metabolism ; Mutation ; Virulence/genetics ; }, abstract = {Candida albicans is a microbial fungus that exists as a commensal member of the human microbiome and an opportunistic pathogen. Cell surface-associated adhesin proteins play a crucial role in C. albicans' ability to undergo cellular morphogenesis, develop robust biofilms, colonize, and cause infection in a host. However, a comprehensive analysis of the role and relationships between these adhesins has not been explored. We previously established a CRISPR-based platform for efficient generation of single- and double-gene deletions in C. albicans, which was used to construct a library of 144 mutants, comprising 12 unique adhesin genes deleted singly, and every possible combination of double deletions. Here, we exploit this adhesin mutant library to explore the role of adhesin proteins in C. albicans virulence. We perform a comprehensive, high-throughput screen of this library, using Caenorhabditis elegans as a simplified model host system, which identified mutants critical for virulence and significant genetic interactions. We perform follow-up analysis to assess the ability of high- and low-virulence strains to undergo cellular morphogenesis and form biofilms in vitro, as well as to colonize the C. elegans host. We further perform genetic interaction analysis to identify novel significant negative genetic interactions between adhesin mutants, whereby combinatorial perturbation of these genes significantly impairs virulence, more than expected based on virulence of the single mutant constituent strains. Together, this study yields important new insight into the role of adhesins, singly and in combinations, in mediating diverse facets of virulence of this critical fungal pathogen.}, }
@article {pmid33723873, year = {2021}, author = {González-Sánchez, P and DeNicola, GM}, title = {The microbiome(s) and cancer: know thy neighbor(s).}, journal = {The Journal of pathology}, volume = {254}, number = {4}, pages = {332-343}, doi = {10.1002/path.5661}, pmid = {33723873}, issn = {1096-9896}, mesh = {Animals ; Humans ; *Microbiota ; *Neoplasms ; }, abstract = {The human microbiome is essential for the correct functioning of many host physiological processes, including metabolic regulation and immune responses. Increasing evidence indicates that the microbiome may also influence cancer development, progression, and the response to therapy. Although most studies have focused on the effect of the gut microbiome, many other organs such as the skin, vagina, and lungs harbor their own microbiomes that are different from the gut. Tumor development has been associated with dysbiosis not only in the gut but also in the tissue from which the tumor originated. Furthermore, the intratumoral microbiota has a distinct signature in each tumor type. Here, we review the mechanisms by which the organ-specific microbiome can contribute to carcinogenesis: release of toxins that cause DNA damage and barrier failure; alteration of immune responses to create a local inflammatory or immunosuppressive environment; and regulation of nutrient levels in the tumor microenvironment through metabolite production and consumption. Solving the puzzle of how the microbiome influences the carcinogenesis process and treatment response requires an understanding of the two ways the microbiome can interact with cancer cells and the tumor microenvironment: through systemic effects exerted by the gut microbiota and local effects of the intratumoral microbiota. © 2021 The Pathological Society of Great Britain and Ireland. Published by John Wiley &amp; Sons, Ltd.}, }
@article {pmid33719117, year = {2021}, author = {Fuentes-Chust, C and Parolo, C and Rosati, G and Rivas, L and Perez-Toralla, K and Simon, S and de Lecuona, I and Junot, C and Trebicka, J and Merkoçi, A}, title = {The Microbiome Meets Nanotechnology: Opportunities and Challenges in Developing New Diagnostic Devices.}, journal = {Advanced materials (Deerfield Beach, Fla.)}, volume = {33}, number = {18}, pages = {e2006104}, doi = {10.1002/adma.202006104}, pmid = {33719117}, issn = {1521-4095}, support = {825694//European Union's Horizon 2020 Research &amp; Innovation Program/ ; //European Commission/ ; //Marie Sk&#x142;odowska-Curie/ ; 795635//European Union's Horizon 2020/ ; }, mesh = {*Microbiota ; Humans ; *Nanotechnology ; Point-of-Care Systems ; Biosensing Techniques/methods/instrumentation ; Nanostructures/chemistry ; }, abstract = {Monitoring of the human microbiome is an emerging area of diagnostics for personalized medicine. Here, the potential of different nanomaterials and nanobiosensing technologies is reviewed for the development of novel diagnostic devices for the detection and measurement of microbiome-related biomarkers. Moreover, the current and future landscape of microbiome-based diagnostics is defined by exploring the advantages and disadvantages of current nanotechnology-based approaches, especially in the context of developing point-of-care (PoC) devices that would meet the international guidelines known as REASSURED (Real-time connectivity; Ease of specimen collection; Affordability; Sensitivity; Specificity; User-friendliness; Rapid &amp; robust operation; Equipment-free; and Deliverability). Finally, the strategies of the latest international scientific consortia working in this field are analyzed, the current microbiome diagnostics market are reported and the principal ethical, legal, and societal issues related to microbiome R&amp;D and innovation are discussed.}, }
@article {pmid33718417, year = {2021}, author = {Zhou, Y and He, Y and Liu, L and Zhou, W and Wang, P and Hu, H and Nie, Y and Chen, Y}, title = {Alterations in Gut Microbial Communities Across Anatomical Locations in Inflammatory Bowel Diseases.}, journal = {Frontiers in nutrition}, volume = {8}, number = {}, pages = {615064}, pmid = {33718417}, issn = {2296-861X}, abstract = {We previously discovered that gut microbiota can serve as universal microbial biomarkers for diagnosis, disease activity assessment, and predicting the response to infliximab treatment for inflammatory bowel diseases (IBD). Much still remains unknown about the relationship between alterations in gut microbiota and IBD affected bowel region, in particular in the case of ulcerative colitis (UC) and colonic Crohn's disease (cCD) without endoscopic and biopsy data. In the current study gut microbiota from a population in China was found to be distinct from that of the Western world [Human Microbiome Project (HMP) data]. Furthermore, both gut microbiota greatly differed from microbiota of other anatomical locations (oral, skin, airway, and vagina), with higher alpha-diversity (Chinese gut > HMP gut > oral microbiome > airway microbiome > skin microbiome > vaginal microbiome), and marked differences in microbiome composition. In patients with IBD in China, UC was characterized by the presence of Gardnerella, while cCD was characterized by the presence of Fusobacterium. Moreover, gut microbiota, such as Gardnerella and Fusobacterium, may be potential biomarkers for identifying UC from cCD. Together, this study revealed crucial differences in microbial communities across anatomical locations, and demonstrated that there was an important association between IBD affected bowel region and gut microbiota.}, }
@article {pmid33713931, year = {2021}, author = {Neckovic, A and van Oorschot, RAH and Szkuta, B and Durdle, A}, title = {Investigation into the presence and transfer of microbiomes within a forensic laboratory setting.}, journal = {Forensic science international. Genetics}, volume = {52}, number = {}, pages = {102492}, doi = {10.1016/j.fsigen.2021.102492}, pmid = {33713931}, issn = {1878-0326}, mesh = {DNA, Bacterial/genetics ; *Equipment Contamination ; Forensic Sciences ; High-Throughput Nucleotide Sequencing ; Humans ; *Laboratories ; Microbiota/*genetics ; Personal Protective Equipment/microbiology ; Sequence Analysis, DNA ; *Touch ; }, abstract = {Microbial profiling within forensic science is an emerging field that may have applications in the identification of individuals using microbial signatures. It is important to determine if microbial transfer may occur within a forensic laboratory setting using current standard operating procedures (SOPs) for nuclear DNA recovery, to assess the suitability of such procedures for microbial profiling and establish the potential limitations of microbial profiling for forensic purposes. This preliminary study investigated the presence and potential transfer of human-associated microbiomes within a forensic laboratory. Swabs of laboratory surfaces, external surfaces of personal protective equipment (PPE) and equipment were taken before and after mock examinations of cotton swatches, which harboured microbiota transferred from direct hand-contact. Microbial profiles obtained from these samples were compared to reference profiles obtained from the participants, cotton swatches and the researcher to detect microbial transfer from the individuals and determine potential source contributions. The results revealed an apparent transfer of microbiota to the examined swatches, laboratory equipment and surfaces from the participants and/or researcher following the mock examinations, highlighting potential contamination issues regarding microbial profiling when using current laboratory SOPs for nuclear DNA recovery, and cleaning.}, }
@article {pmid33713524, year = {2021}, author = {Ponziani, FR and Picca, A and Marzetti, E and Calvani, R and Conta, G and Del Chierico, F and Capuani, G and Faccia, M and Fianchi, F and Funaro, B and Josè Coelho-Junior, H and Petito, V and Rinninella, E and Paroni Sterbini, F and Reddel, S and Vernocchi, P and Cristina Mele, M and Miccheli, A and Putignani, L and Sanguinetti, M and Pompili, M and Gasbarrini, A and , }, title = {Characterization of the gut-liver-muscle axis in cirrhotic patients with sarcopenia.}, journal = {Liver international : official journal of the International Association for the Study of the Liver}, volume = {41}, number = {6}, pages = {1320-1334}, doi = {10.1111/liv.14876}, pmid = {33713524}, issn = {1478-3231}, mesh = {*Frailty ; *Gastrointestinal Microbiome ; Humans ; Liver Cirrhosis/complications ; *Sarcopenia ; }, abstract = {BACKGROUND &amp; AIM: Sarcopenia is frequent in cirrhosis and is associated with unfavourable outcomes. The role of the gut-liver-muscle axis in this setting has been poorly investigated. The aim of this study was to identify gut microbiota, metabolic and inflammatory signatures associated with sarcopenia in cirrhotic patients.<br><br>METHODS: Fifty cirrhotic patients assessed for the presence of sarcopenia by the quantification of muscle mass and strength were compared with age- and sex-matched controls. A multiomic analysis, including gut microbiota composition and metabolomics, serum myokines and systemic and intestinal inflammatory mediators, was performed.<br><br>RESULTS: The gut microbiota of sarcopenic cirrhotic patients was poor in bacteria associated with physical function (Methanobrevibacter, Prevotella and Akkermansia), and was enriched in Eggerthella, a gut microbial marker of frailty. The abundance of potentially pathogenic bacteria, such as Klebsiella, was also increased, to the detriment of autochthonous ones. Sarcopenia was associated with elevated serum levels of pro-inflammatory mediators and of fibroblast growth factor 21 (FGF21) in cirrhotic patients. Gut microbiota metabolic pathways involved in amino acid, protein and branched-chain amino acid metabolism were up-regulated, in addition to ethanol, trimethylamine and dimethylamine production. Correlation networks and clusters of variables associated with sarcopenia were identified, including one centred on Klebsiella/ethanol/FGF21/Eggerthella/Prevotella.<br><br>CONCLUSIONS: Alterations in the gut-liver-muscle axis are associated with sarcopenia in patients with cirrhosis. Detrimental but also compensatory functions are involved in this complex network.}, }
@article {pmid33711013, year = {2021}, author = {Shestopaloff, K and Dong, M and Gao, F and Xu, W}, title = {DCMD: Distance-based classification using mixture distributions on microbiome data.}, journal = {PLoS computational biology}, volume = {17}, number = {3}, pages = {e1008799}, pmid = {33711013}, issn = {1553-7358}, mesh = {Algorithms ; Computational Biology/*methods ; Gastrointestinal Microbiome/*genetics ; High-Throughput Nucleotide Sequencing ; Humans ; *Machine Learning ; }, abstract = {Current advances in next-generation sequencing techniques have allowed researchers to conduct comprehensive research on the microbiome and human diseases, with recent studies identifying associations between the human microbiome and health outcomes for a number of chronic conditions. However, microbiome data structure, characterized by sparsity and skewness, presents challenges to building effective classifiers. To address this, we present an innovative approach for distance-based classification using mixture distributions (DCMD). The method aims to improve classification performance using microbiome community data, where the predictors are composed of sparse and heterogeneous count data. This approach models the inherent uncertainty in sparse counts by estimating a mixture distribution for the sample data and representing each observation as a distribution, conditional on observed counts and the estimated mixture, which are then used as inputs for distance-based classification. The method is implemented into a k-means classification and k-nearest neighbours framework. We develop two distance metrics that produce optimal results. The performance of the model is assessed using simulated and human microbiome study data, with results compared against a number of existing machine learning and distance-based classification approaches. The proposed method is competitive when compared to the other machine learning approaches, and shows a clear improvement over commonly used distance-based classifiers, underscoring the importance of modelling sparsity for achieving optimal results. The range of applicability and robustness make the proposed method a viable alternative for classification using sparse microbiome count data. The source code is available at https://github.com/kshestop/DCMD for academic use.}, }
@article {pmid33704660, year = {2021}, author = {Tiwari, RK and Moin, A and Rizvi, SMD and Shahid, SMA and Bajpai, P}, title = {Modulating neuroinflammation in neurodegeneration-related dementia: can microglial toll-like receptors pull the plug?.}, journal = {Metabolic brain disease}, volume = {36}, number = {5}, pages = {829-847}, pmid = {33704660}, issn = {1573-7365}, mesh = {Animals ; Brain/*metabolism/pathology ; Dementia/*metabolism/pathology ; Humans ; Inflammation/*metabolism/pathology ; Microglia/*metabolism/pathology ; Nerve Degeneration/*metabolism/pathology ; Toll-Like Receptors/*metabolism ; }, abstract = {Neurodegeneration-associated dementia disorders (NADDs), namely Alzheimer and Parkinson diseases, are developed by a significant portion of the elderly population globally. Extensive research has provided critical insights into the molecular basis of the pathological advancements of these diseases, but an efficient curative therapy seems elusive. A common attribute of NADDs is neuroinflammation due to a chronic inflammatory response within the central nervous system (CNS), which is primarily modulated by microglia. This response within the CNS is positively regulated by cytokines, chemokines, secondary messengers or cyclic nucleotides, and free radicals. Microglia mediated immune activation is regulated by a positive feedback loop in NADDs. The present review focuses on evaluating the crosstalk between inflammatory mediators and microglia, which aggravates both the clinical progression and extent of NADDs by forming a persistent chronic inflammatory milieu within the CNS. We also discuss the role of the human gut microbiota and its effect on NADDs as well as the suitability of targeting toll-like receptors for an immunotherapeutic intervention targeting the deflation of an inflamed milieu within the CNS.}, }
@article {pmid33692771, year = {2021}, author = {Moreno-Indias, I and Lahti, L and Nedyalkova, M and Elbere, I and Roshchupkin, G and Adilovic, M and Aydemir, O and Bakir-Gungor, B and Santa Pau, EC and D'Elia, D and Desai, MS and Falquet, L and Gundogdu, A and Hron, K and Klammsteiner, T and Lopes, MB and Marcos-Zambrano, LJ and Marques, C and Mason, M and May, P and Pašić, L and Pio, G and Pongor, S and Promponas, VJ and Przymus, P and Saez-Rodriguez, J and Sampri, A and Shigdel, R and Stres, B and Suharoschi, R and Truu, J and Truică, CO and Vilne, B and Vlachakis, D and Yilmaz, E and Zeller, G and Zomer, AL and Gómez-Cabrero, D and Claesson, MJ}, title = {Statistical and Machine Learning Techniques in Human Microbiome Studies: Contemporary Challenges and Solutions.}, journal = {Frontiers in microbiology}, volume = {12}, number = {}, pages = {635781}, pmid = {33692771}, issn = {1664-302X}, abstract = {The human microbiome has emerged as a central research topic in human biology and biomedicine. Current microbiome studies generate high-throughput omics data across different body sites, populations, and life stages. Many of the challenges in microbiome research are similar to other high-throughput studies, the quantitative analyses need to address the heterogeneity of data, specific statistical properties, and the remarkable variation in microbiome composition across individuals and body sites. This has led to a broad spectrum of statistical and machine learning challenges that range from study design, data processing, and standardization to analysis, modeling, cross-study comparison, prediction, data science ecosystems, and reproducible reporting. Nevertheless, although many statistics and machine learning approaches and tools have been developed, new techniques are needed to deal with emerging applications and the vast heterogeneity of microbiome data. We review and discuss emerging applications of statistical and machine learning techniques in human microbiome studies and introduce the COST Action CA18131 "ML4Microbiome" that brings together microbiome researchers and machine learning experts to address current challenges such as standardization of analysis pipelines for reproducibility of data analysis results, benchmarking, improvement, or development of existing and new tools and ontologies.}, }
@article {pmid33682945, year = {2021}, author = {Bar, J and Sarig, O and Lotan-Pompan, M and Dassa, B and Miodovnik, M and Weinberger, A and Sprecher, E and Segal, E and Samuelov, L}, title = {Evidence for cutaneous dysbiosis in dystrophic epidermolysis bullosa.}, journal = {Clinical and experimental dermatology}, volume = {46}, number = {7}, pages = {1223-1229}, doi = {10.1111/ced.14592}, pmid = {33682945}, issn = {1365-2230}, support = {//EB Research Partnership foundation/ ; }, mesh = {Adolescent ; Adult ; Bacteria/*isolation &amp; purification ; Case-Control Studies ; Child, Preschool ; Dysbiosis/*complications ; Epidermolysis Bullosa Dystrophica/complications/genetics/*microbiology ; Genotype ; Humans ; *Microbiota ; Skin/*microbiology ; Staphylococcus/isolation &amp; purification ; Young Adult ; }, abstract = {BACKGROUND: The human microbiome project addresses the relationship between bacterial flora and the human host, in both healthy and diseased conditions. The skin is an ecosystem with multiple niches, each featuring unique physiological conditions and thus hosting different bacterial populations. The skin microbiome has been implicated in the pathogenesis of many dermatoses. Given the role of dysbiosis in the pathogenesis of inflammation, which is prominent in dystrophic epidermolysis bullosa (DEB), we undertook a study on the skin microbiome.<br><br>AIM: To characterize the skin microbiome in a series of patients with DEB.<br><br>METHODS: This was a case-control study of eight patients with DEB and nine control cases enrolled between June 2017 and November 2018. The skin of patients with DEB was sampled at three different sites: untreated wound, perilesional skin and normal-appearing (uninvolved) skin. Normal skin on the forearm was sampled from age-matched healthy controls (HCs). We used a dedicated DNA extraction protocol to isolate microbial DNA, which was then analysed using next-generation microbial 16S rRNA sequencing. Data were analysed using a series of advanced bioinformatics tools.<br><br>RESULTS: The wounds, perilesional and uninvolved skin of patients with DEB demonstrated reduced bacterial diversity compared with HCs, with the flora in DEB wounds being the least diverse. We found an increased prevalence of staphylococci species in the lesional and perilesional skin of patients with DEB, compared with their uninvolved, intact skin. Similarly, the uninvolved skin of patients with DEB displayed increased staphylococcal content and significantly different microbiome diversities (other than staphylococci) compared with HC skin.<br><br>CONCLUSIONS: These findings suggest the existence of a unique DEB-associated skin microbiome signature, which could be targeted by specific pathogen-directed therapies. Moreover, altering the skin microbiome with increasing colonization of bacteria associated with nonchronic wounds may potentially facilitate wound healing in patients with DEB.}, }
@article {pmid33680992, year = {2021}, author = {Poddighe, D and Kushugulova, A}, title = {Salivary Microbiome in Pediatric and Adult Celiac Disease.}, journal = {Frontiers in cellular and infection microbiology}, volume = {11}, number = {}, pages = {625162}, pmid = {33680992}, issn = {2235-2988}, mesh = {Adult ; *Celiac Disease ; Child ; Duodenum ; *Gastrointestinal Microbiome ; Glutens ; Humans ; *Microbiota ; }, abstract = {The human salivary microbiota includes hundreds of bacterial species. Alterations in gut microbiota have been explored in Celiac Disease (CD), but fewer studies investigated the characteristics of salivary microbiome in these patients, despite the potential implications in its pathogenesis. Indeed, some recent studies suggested that the partial digestion of gluten proteins by some bacteria may affect the array of gluten peptides reaching the gut and the way by which those are presented to the intestinal immune system. The available clinical studies investigating the salivary microbiota in children and adults, are insufficient to make any reliable conclusion, even though some bacterial species/phyla differences have been reported between celiac patients and controls. However, the salivary microbiome could correlate better with the duodenal microbiota, than the fecal one. Therefore, further clinical studies on salivary microbiome by different and independent research groups and including different populations, are advisable in order to explore the usefulness of the salivary microbiome analysis and understand some aspects of CD pathogenesis with potential clinical and practical implications.}, }
@article {pmid33680353, year = {2021}, author = {Ghannam, RB and Techtmann, SM}, title = {Machine learning applications in microbial ecology, human microbiome studies, and environmental monitoring.}, journal = {Computational and structural biotechnology journal}, volume = {19}, number = {}, pages = {1092-1107}, pmid = {33680353}, issn = {2001-0370}, abstract = {Advances in nucleic acid sequencing technology have enabled expansion of our ability to profile microbial diversity. These large datasets of taxonomic and functional diversity are key to better understanding microbial ecology. Machine learning has proven to be a useful approach for analyzing microbial community data and making predictions about outcomes including human and environmental health. Machine learning applied to microbial community profiles has been used to predict disease states in human health, environmental quality and presence of contamination in the environment, and as trace evidence in forensics. Machine learning has appeal as a powerful tool that can provide deep insights into microbial communities and identify patterns in microbial community data. However, often machine learning models can be used as black boxes to predict a specific outcome, with little understanding of how the models arrived at predictions. Complex machine learning algorithms often may value higher accuracy and performance at the sacrifice of interpretability. In order to leverage machine learning into more translational research related to the microbiome and strengthen our ability to extract meaningful biological information, it is important for models to be interpretable. Here we review current trends in machine learning applications in microbial ecology as well as some of the important challenges and opportunities for more broad application of machine learning to understanding microbial communities.}, }
@article {pmid33679632, year = {2021}, author = {Lee, LH and Wong, SH and Chin, SF and Singh, V and Ab Mutalib, NS}, title = {Editorial: Human Microbiome: Symbiosis to Pathogenesis.}, journal = {Frontiers in microbiology}, volume = {12}, number = {}, pages = {605783}, pmid = {33679632}, issn = {1664-302X}, }
@article {pmid33675857, year = {2021}, author = {Spichak, S and Bastiaanssen, TFS and Berding, K and Vlckova, K and Clarke, G and Dinan, TG and Cryan, JF}, title = {Mining microbes for mental health: Determining the role of microbial metabolic pathways in human brain health and disease.}, journal = {Neuroscience and biobehavioral reviews}, volume = {125}, number = {}, pages = {698-761}, doi = {10.1016/j.neubiorev.2021.02.044}, pmid = {33675857}, issn = {1873-7528}, mesh = {Brain ; *Gastrointestinal Microbiome ; Humans ; *Mental Health ; Metabolic Networks and Pathways ; Reproducibility of Results ; }, abstract = {There is increasing knowledge regarding the role of the microbiome in modulating the brain and behaviour. Indeed, the actions of microbial metabolites are key for appropriate gut-brain communication in humans. Among these metabolites, short-chain fatty acids, tryptophan, and bile acid metabolites/pathways show strong preclinical evidence for involvement in various aspects of brain function and behaviour. With the identification of neuroactive gut-brain modules, new predictive tools can be applied to existing datasets. We identified 278 studies relating to the human microbiota-gut-brain axis which included sequencing data. This spanned across psychiatric and neurological disorders with a small number also focused on normal behavioural development. With a consistent bioinformatics pipeline, thirty-five of these datasets were reanalysed from publicly available raw sequencing files and the remainder summarised and collated. Among the reanalysed studies, we uncovered evidence of disease-related alterations in microbial metabolic pathways in Alzheimer's Disease, schizophrenia, anxiety and depression. Amongst studies that could not be reanalysed, many sequencing and technical limitations hindered the discovery of specific biomarkers of microbes or metabolites conserved across studies. Future studies are warranted to confirm our findings. We also propose guidelines for future human microbiome analysis to increase reproducibility and consistency within the field.}, }
@article {pmid33674782, year = {2021}, author = {Nuzzo, A and Saha, S and Berg, E and Jayawickreme, C and Tocker, J and Brown, JR}, title = {Expanding the drug discovery space with predicted metabolite-target interactions.}, journal = {Communications biology}, volume = {4}, number = {1}, pages = {288}, pmid = {33674782}, issn = {2399-3642}, mesh = {Anti-Inflammatory Agents/*pharmacology ; Bacteria/immunology/*metabolism ; Cells, Cultured ; Data Mining ; Databases, Factual ; *Drug Discovery ; Gastrointestinal Agents/*pharmacology ; *Gastrointestinal Microbiome ; Gene Expression Profiling ; Host-Pathogen Interactions ; Humans ; Inflammatory Bowel Diseases/*drug therapy/immunology/metabolism/microbiology ; Ligands ; *Machine Learning ; Metabolome ; Metabolomics ; Molecular Targeted Therapy ; *Protein Interaction Maps ; Signal Transduction ; Transcriptome ; }, abstract = {Metabolites produced in the human gut are known modulators of host immunity. However, large-scale identification of metabolite-host receptor interactions remains a daunting challenge. Here, we employed computational approaches to identify 983 potential metabolite-target interactions using the Inflammatory Bowel Disease (IBD) cohort dataset of the Human Microbiome Project 2 (HMP2). Using a consensus of multiple machine learning methods, we ranked metabolites based on importance to IBD, followed by virtual ligand-based screening to identify possible human targets and adding evidence from compound assay, differential gene expression, pathway enrichment, and genome-wide association studies. We confirmed known metabolite-target pairs such as nicotinic acid-GPR109a or linoleoyl ethanolamide-GPR119 and inferred interactions of interest including oleanolic acid-GABRG2 and alpha-CEHC-THRB. Eleven metabolites were tested for bioactivity in vitro using human primary cell-types. By expanding the universe of possible microbial metabolite-host protein interactions, we provide multiple drug targets for potential immune-therapies.}, }
@article {pmid33671853, year = {2021}, author = {Huang, E and Kim, S and Ahn, T}, title = {Deep Learning for Integrated Analysis of Insulin Resistance with Multi-Omics Data.}, journal = {Journal of personalized medicine}, volume = {11}, number = {2}, pages = {}, pmid = {33671853}, issn = {2075-4426}, support = {P0009477, 2020//This research is supported through the Ministry of Trade, Industry and Energy(MOTIE)/ ; }, abstract = {Technological advances in next-generation sequencing (NGS) have made it possible to uncover extensive and dynamic alterations in diverse molecular components and biological pathways across healthy and diseased conditions. Large amounts of multi-omics data originating from emerging NGS experiments require feature engineering, which is a crucial step in the process of predictive modeling. The underlying relationship among multi-omics features in terms of insulin resistance is not well understood. In this study, using the multi-omics data of type II diabetes from the Integrative Human Microbiome Project, from 10,783 features, we conducted a data analytic approach to elucidate the relationship between insulin resistance and multi-omics features, including microbiome data. To better explain the impact of microbiome features on insulin classification, we used a developed deep neural network interpretation algorithm for each microbiome feature's contribution to the discriminative model output in the samples.}, }
@article {pmid33671308, year = {2021}, author = {Koshy-Chenthittayil, S and Archambault, L and Senthilkumar, D and Laubenbacher, R and Mendes, P and Dongari-Bagtzoglou, A}, title = {Agent Based Models of Polymicrobial Biofilms and the Microbiome-A Review.}, journal = {Microorganisms}, volume = {9}, number = {2}, pages = {}, pmid = {33671308}, issn = {2076-2607}, support = {R01 DE013986/DE/NIDCR NIH HHS/United States ; R01 GM127909/GM/NIGMS NIH HHS/United States ; U01 EB024501/EB/NIBIB NIH HHS/United States ; 1R01GM127909-01,1R011AI135128-01, 1U01EB024501-01, RO1DE013986/NH/NIH HHS/United States ; }, abstract = {The human microbiome has been a focus of intense study in recent years. Most of the living organisms comprising the microbiome exist in the form of biofilms on mucosal surfaces lining our digestive, respiratory, and genito-urinary tracts. While health-associated microbiota contribute to digestion, provide essential nutrients, and protect us from pathogens, disturbances due to illness or medical interventions contribute to infections, some that can be fatal. Myriad biological processes influence the make-up of the microbiota, for example: growth, division, death, and production of extracellular polymers (EPS), and metabolites. Inter-species interactions include competition, inhibition, and symbiosis. Computational models are becoming widely used to better understand these interactions. Agent-based modeling is a particularly useful computational approach to implement the various complex interactions in microbial communities when appropriately combined with an experimental approach. In these models, each cell is represented as an autonomous agent with its own set of rules, with different rules for each species. In this review, we will discuss innovations in agent-based modeling of biofilms and the microbiota in the past five years from the biological and mathematical perspectives and discuss how agent-based models can be further utilized to enhance our comprehension of the complex world of polymicrobial biofilms and the microbiome.}, }
@article {pmid33669932, year = {2021}, author = {Pane, S and Sacco, A and Iorio, A and Romani, L and Putignani, L}, title = {Strongyloides stercoralis Infestation in a Child: How a Nematode Can Affect Gut Microbiota.}, journal = {International journal of molecular sciences}, volume = {22}, number = {4}, pages = {}, pmid = {33669932}, issn = {1422-0067}, support = {Ricerca Corrente 201905_ Genetica_Putignani and 202005_ Genetica_Putignani//Italian Ministry of Health/ ; }, mesh = {Animals ; Biodiversity ; Child ; Cluster Analysis ; Female ; *Gastrointestinal Microbiome ; Humans ; Phylogeny ; Principal Component Analysis ; Strongyloides stercoralis/genetics/isolation &amp; purification/*physiology ; Strongyloidiasis/metabolism/*microbiology/*parasitology ; }, abstract = {Background: Strongyloidiasis is a neglected tropical disease caused by the intestinal nematode Strongyloides stercoralis and characterized by gastrointestinal and pulmonary involvement. We report a pediatric case of strongyloidiasis to underline the response of the host microbiota to the perturbation induced by the nematode. Methods: We performed a 16S rRNA-metagenomic analysis of the gut microbiota of a 7-year-old female during and after S. stercolaris infection, investigating three time-point of stool samples' ecology: T0- during parasite infection, T1- a month after parasite infection, and T2- two months after parasite infection. Targeted-metagenomics were used to investigate ecology and to predict the functional pathways of the gut microbiota. Results: an increase in the alpha-diversity indices in T0-T1 samples was observed compared to T2 and healthy controls (CTRLs). Beta-diversity analysis showed a shift in the relative abundance of specific gut bacterial species from T0 to T2 samples. Moreover, the functional prediction of the targeted-metagenomics profiles suggested an enrichment of microbial glycan and carbohydrate metabolisms in the T0 sample compared with CTRLs. Conclusions: The herein report reinforces the literature suggestion of a putative direct or immune-mediated ability of S. stercolaris to promote the increase in bacterial diversity.}, }
@article {pmid33668910, year = {2021}, author = {Petrova, P and Ivanov, I and Tsigoriyna, L and Valcheva, N and Vasileva, E and Parvanova-Mancheva, T and Arsov, A and Petrov, K}, title = {Traditional Bulgarian Dairy Products: Ethnic Foods with Health Benefits.}, journal = {Microorganisms}, volume = {9}, number = {3}, pages = {}, pmid = {33668910}, issn = {2076-2607}, support = {National Research Programme approved by DCM # 577/17.08.2018//Bulgarian Ministry of Education and Science with financial support by the "Healthy Foods for a Strong Bio-Economy and Quality of Life",/ ; Contract KP-06-COST7 with national co-financing to COST Action 18101//National Scientific Fund, Republic of Bulgaria/ ; }, abstract = {The reported health effects of fermented dairy foods, which are traditionally manufactured in Bulgaria, are connected with their microbial biodiversity. The screening and development of probiotic starters for dairy products with unique properties are based exclusively on the isolation and characterization of lactic acid bacterial (LAB) strains. This study aims to systematically describe the LAB microbial content of artisanal products such as Bulgarian-type yoghurt, white brined cheese, kashkaval, koumiss, kefir, katak, and the Rhodope's brano mliako. The original technologies for their preparation preserve the valuable microbial content and improve their nutritional and probiotic qualities. This review emphasises the features of LAB starters and the autochthonous microflora, the biochemistry of dairy food production, and the approaches for achieving the fortification of the foods with prebiotics, bioactive peptides (ACE2-inhibitors, bacteriocins, cyclic peptides with antimicrobial activity), immunomodulatory exopolysaccharides, and other metabolites (indol-3-propionic acid, free amino acids, antioxidants, prebiotics) with reported beneficial effects on human health. The link between the microbial content of dairy foods and the healthy human microbiome is highlighted.}, }
@article {pmid33668618, year = {2021}, author = {Salem, M and Pajunen, MI and Jun, JW and Skurnik, M}, title = {T4-like Bacteriophages Isolated from Pig Stools Infect Yersinia pseudotuberculosis and Yersinia pestis Using LPS and OmpF as Receptors.}, journal = {Viruses}, volume = {13}, number = {2}, pages = {}, pmid = {33668618}, issn = {1999-4915}, mesh = {Animals ; Bacterial Proteins/genetics/*metabolism ; Bacteriophages/classification/genetics/*isolation &amp; purification/physiology ; Base Composition ; Feces/*virology ; Genome, Viral ; Host Specificity ; Lipopolysaccharides/*metabolism ; Phylogeny ; Porins/genetics/*metabolism ; Receptors, Virus/genetics/*metabolism ; Swine ; Yersinia pestis/genetics/metabolism/*virology ; Yersinia pseudotuberculosis/genetics/metabolism/*virology ; }, abstract = {The Yersinia bacteriophages fPS-2, fPS-65, and fPS-90, isolated from pig stools, have long contractile tails and elongated heads, and they belong to genus Tequatroviruses in the order Caudovirales. The phages exhibited relatively wide host ranges among Yersinia pseudotuberculosis and related species. One-step growth curve experiments revealed that the phages have latent periods of 50-80 min with burst sizes of 44-65 virions per infected cell. The phage genomes consist of circularly permuted dsDNA of 169,060, 167,058, and 167,132 bp in size, respectively, with a G + C content 35.3%. The number of predicted genes range from 267 to 271. The phage genomes are 84-92% identical to each other and ca 85% identical to phage T4. The phage receptors were identified by whole genome sequencing of spontaneous phage-resistant mutants. The phage-resistant strains had mutations in the ompF, galU, hldD, or hldE genes. OmpF is a porin, and the other genes encode lipopolysaccharide (LPS) biosynthetic enzymes. The ompF, galU, and hldE mutants were successfully complemented in trans with respective wild-type genes. The host recognition was assigned to long tail fiber tip protein Gp38, analogous to that of T-even phages such as Salmonella phage S16, specifically to the distal β-helices connecting loops.}, }
@article {pmid33665201, year = {2020}, author = {Bassaganya-Riera, J and Berry, EM and Blaak, EE and Burlingame, B and le Coutre, J and van Eden, W and El-Sohemy, A and German, JB and Knorr, D and Lacroix, C and Muscaritoli, M and Nieman, DC and Rychlik, M and Scholey, A and Serafini, M}, title = {Goals in Nutrition Science 2020-2025.}, journal = {Frontiers in nutrition}, volume = {7}, number = {}, pages = {606378}, pmid = {33665201}, issn = {2296-861X}, abstract = {Five years ago, with the editorial board of Frontiers in Nutrition, we took a leap of faith to outline the Goals for Nutrition Science - the way we see it (1). Now, in 2020, we can put ourselves to the test and take a look back. Without a doubt we got it right with several of the key directions. To name a few, Sustainable Development Goals (SDGs) for Food and Nutrition are part of the global public agenda, and the SDGs contribute to the structuring of international science and research. Nutritional Science has become a critical element in strengthening work on the SDGs, and the development of appropriate methodologies is built on the groundwork of acquiring and analyzing big datasets. Investigation of the Human Microbiome is providing novel insight on the interrelationship between nutrition, the immune system and disease. Finally, with an advanced definition of the gut-brain-axis we are getting a glimpse into the potential for Nutrition and Brain Health. Various milestones have been achieved, and any look into the future will have to consider the lessons learned from Covid-19 and the sobering awareness about the frailty of our food systems in ensuring global food security. With a view into the coming 5 years from 2020 to 2025, the editorial board has taken a slightly different approach as compared to the previous Goals article. A mind map has been created to outline the key topics in nutrition science. Not surprisingly, when looking ahead, the majority of scientific investigation required will be in the areas of health and sustainability. Johannes le Coutre, Field Chief Editor, Frontiers in Nutrition.}, }
@article {pmid33664779, year = {2021}, author = {Ma, ZS}, title = {Niche-neutral theoretic approach to mechanisms underlying the biodiversity and biogeography of human microbiomes.}, journal = {Evolutionary applications}, volume = {14}, number = {2}, pages = {322-334}, pmid = {33664779}, issn = {1752-4571}, abstract = {The human microbiome consists of five major regional biomes distributed in or on our five body sites including skin, oral, lung, gut, and reproductive tract. Its biogeography (the spatial and temporal distribution of its biodiversity) has far-reaching implications to our health and diseases. Nevertheless, we currently have very limited understanding on the mechanisms shaping the biogeography, since it is often rather difficult to determine the relative importance of drift, dispersal, speciation, and selection, the four processes (mechanisms) determining the patterns of microbial biogeography and community dynamics according to a recent synthesis in community ecology and biogeography. To disentangle these mechanisms, I utilize multisite neutral (MSN) model and niche-neutral hybrid (NNH) model to analyze large number of truly multisite microbiome samples covering all five major human microbiome habitats, including 699 metacommunities and 5,420 local communities. Approximately 89% of metacommunities and 92% local communities exhibit patterns indistinguishable from neutral, and 20% indistinguishable from niche-neutral hybrid model, indicating the relative significance of stochastic neutral forces versus deterministic niche selection in shaping the biogeography of human microbiome. These findings cast supporting evidence to van der Gast's revision to classic Bass-Becking doctrine of microbial biogeography: "Some things are everywhere and some things are not. Sometimes the environment selects and sometimes it doesn't," offering the first educated guess for "some" and "sometimes" in the revised doctrine. Furthermore, the logistic/Cox regression models describing the relationships among community neutrality, niche differentiation, and key community/species characteristics (including community diversity, community/species dominance, speciation, and migration rates) were constructed to quantitatively describe the niche-neutral continuum and the influences of community/species properties on the continuum.}, }
@article {pmid33653893, year = {2021}, author = {Engevik, MA and Danhof, HA and Ruan, W and Engevik, AC and Chang-Graham, AL and Engevik, KA and Shi, Z and Zhao, Y and Brand, CK and Krystofiak, ES and Venable, S and Liu, X and Hirschi, KD and Hyser, JM and Spinler, JK and Britton, RA and Versalovic, J}, title = {Fusobacterium nucleatum Secretes Outer Membrane Vesicles and Promotes Intestinal Inflammation.}, journal = {mBio}, volume = {12}, number = {2}, pages = {}, pmid = {33653893}, issn = {2150-7511}, support = {P30 DK123704/DK/NIDDK NIH HHS/United States ; P30 DK058404/DK/NIDDK NIH HHS/United States ; F32 AI136404/AI/NIAID NIH HHS/United States ; K01 DK123195/DK/NIDDK NIH HHS/United States ; K01 DK121869/DK/NIDDK NIH HHS/United States ; P30 DK056338/DK/NIDDK NIH HHS/United States ; P30 DK020593/DK/NIDDK NIH HHS/United States ; P30 CA068485/CA/NCI NIH HHS/United States ; F30 DK112563/DK/NIDDK NIH HHS/United States ; T32 DK007664/DK/NIDDK NIH HHS/United States ; U24 DK059637/DK/NIDDK NIH HHS/United States ; R01 AI123278/AI/NIAID NIH HHS/United States ; P30 EY008126/EY/NEI NIH HHS/United States ; R01 DK103759/DK/NIDDK NIH HHS/United States ; R01 DK115507/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Bacterial Outer Membrane/*immunology ; Cells, Cultured ; Colon/cytology ; Culture Media/pharmacology ; Cytokines/analysis/immunology ; Epithelial Cells/drug effects/immunology ; Extracellular Vesicles/*immunology ; Female ; Fusobacterium nucleatum/*immunology/*metabolism/pathogenicity ; Gastrointestinal Microbiome ; HT29 Cells ; Humans ; Inflammation/immunology/*microbiology ; Intestines/immunology/microbiology/pathology ; Male ; Mice ; Mice, Inbred C57BL ; NF-kappa B/immunology ; Signal Transduction ; Toll-Like Receptor 4/immunology ; }, abstract = {Multiple studies have implicated microbes in the development of inflammation, but the mechanisms remain unknown. Bacteria in the genus Fusobacterium have been identified in the intestinal mucosa of patients with digestive diseases; thus, we hypothesized that Fusobacterium nucleatum promotes intestinal inflammation. The addition of >50 kDa F. nucleatum conditioned media, which contain outer membrane vesicles (OMVs), to colonic epithelial cells stimulated secretion of the proinflammatory cytokines interleukin-8 (IL-8) and tumor necrosis factor (TNF). In addition, purified F. nucleatum OMVs, but not compounds <50 kDa, stimulated IL-8 and TNF production; which was decreased by pharmacological inhibition of Toll-like receptor 4 (TLR4). These effects were linked to downstream effectors p-ERK, p-CREB, and NF-κB. F. nucleatum >50-kDa compounds also stimulated TNF secretion, p-ERK, p-CREB, and NF-κB activation in human colonoid monolayers. In mice harboring a human microbiota, pretreatment with antibiotics and a single oral gavage of F. nucleatum resulted in inflammation. Compared to mice receiving vehicle control, mice treated with F. nucleatum showed disruption of the colonic architecture, with increased immune cell infiltration and depleted mucus layers. Analysis of mucosal gene expression revealed increased levels of proinflammatory cytokines (KC, TNF, IL-6, IFN-γ, and MCP-1) at day 3 and day 5 in F. nucleatum-treated mice compared to controls. These proinflammatory effects were absent in mice who received F. nucleatum without pretreatment with antibiotics, suggesting that an intact microbiome is protective against F. nucleatum-mediated immune responses. These data provide evidence that F. nucleatum promotes proinflammatory signaling cascades in the context of a depleted intestinal microbiome.IMPORTANCE Several studies have identified an increased abundance of Fusobacterium in the intestinal tracts of patients with colon cancer, liver cirrhosis, primary sclerosing cholangitis, gastroesophageal reflux disease, HIV infection, and alcoholism. However, the direct mechanism(s) of action of Fusobacterium on pathophysiological within the gastrointestinal tract is unclear. These studies have identified that F. nucleatum subsp. polymorphum releases outer membrane vesicles which activate TLR4 and NF-κB to stimulate proinflammatory signals in vitro Using mice harboring a human microbiome, we demonstrate that F. nucleatum can promote inflammation, an effect which required antibiotic-mediated alterations in the gut microbiome. Collectively, these results suggest a mechanism by which F. nucleatum may contribute to intestinal inflammation.}, }
@article {pmid33652903, year = {2021}, author = {Khor, B and Snow, M and Herrman, E and Ray, N and Mansukhani, K and Patel, KA and Said-Al-Naief, N and Maier, T and Machida, CA}, title = {Interconnections Between the Oral and Gut Microbiomes: Reversal of Microbial Dysbiosis and the Balance Between Systemic Health and Disease.}, journal = {Microorganisms}, volume = {9}, number = {3}, pages = {}, pmid = {33652903}, issn = {2076-2607}, abstract = {The human microbiota represents a complex array of microbial species that influence the balance between the health and pathology of their surrounding environment. These microorganisms impart important biological benefits to their host, such as immune regulation and resistance to pathogen colonization. Dysbiosis of microbial communities in the gut and mouth precede many oral and systemic diseases such as cancer, autoimmune-related conditions, and inflammatory states, and can involve the breakdown of innate barriers, immune dysregulation, pro-inflammatory signaling, and molecular mimicry. Emerging evidence suggests that periodontitis-associated pathogens can translocate to distant sites to elicit severe local and systemic pathologies, which necessitates research into future therapies. Fecal microbiota transplantation, probiotics, prebiotics, and synbiotics represent current modes of treatment to reverse microbial dysbiosis through the introduction of health-related bacterial species and substrates. Furthermore, the emerging field of precision medicine has been shown to be an effective method in modulating host immune response through targeting molecular biomarkers and inflammatory mediators. Although connections between the human microbiome, immune system, and systemic disease are becoming more apparent, the complex interplay and future innovations in treatment modalities will become elucidated through continued research and cross-disciplinary collaboration.}, }
@article {pmid33652548, year = {2021}, author = {Puebla-Barragan, S and Reid, G}, title = {Probiotics in Cosmetic and Personal Care Products: Trends and Challenges.}, journal = {Molecules (Basel, Switzerland)}, volume = {26}, number = {5}, pages = {}, pmid = {33652548}, issn = {1420-3049}, support = {692895//Consejo Nacional de Ciencia y Tecnolog&#xed;a/ ; }, mesh = {Cosmetic Techniques/*trends ; Cosmetics/economics/*therapeutic use ; Humans ; Industry/economics ; Probiotics/economics/*therapeutic use ; }, abstract = {Probiotics, defined as "live microorganisms that, when administered in adequate amounts, confer a health benefit on the host," are becoming increasingly popular and marketable. However, too many of the products currently labelled as probiotics fail to comply with the defining characteristics. In recent years, the cosmetic industry has increased the number of products classified as probiotics. While there are several potential applications for probiotics in personal care products, specifically for oral, skin, and intimate care, proper regulation of the labelling and marketing standards is still required to guarantee that consumers are indeed purchasing a probiotic product. This review explores the current market, regulatory aspects, and potential applications of probiotics in the personal care industry.}, }
@article {pmid33649549, year = {2021}, author = {Ipe, DS and Sullivan, MJ and Goh, KGK and Hashimi, SM and Munn, AL and Ulett, GC}, title = {Conserved bacterial de novo guanine biosynthesis pathway enables microbial survival and colonization in the environmental niche of the urinary tract.}, journal = {The ISME journal}, volume = {15}, number = {7}, pages = {2158-2162}, pmid = {33649549}, issn = {1751-7370}, mesh = {Bacteria/genetics ; Guanine ; Humans ; *Microbiota ; *Urinary Tract ; }, abstract = {In bacteria, guaA encodes guanosine monophosphate synthetase that confers an ability to biosynthesize guanine nucleotides de novo. This enables bacterial colonization in different environments and, while guaA is widely distributed among Bacteroidetes and Firmicutes, its contribution to the inhabitation of the human microbiome by commensal bacteria is unclear. We studied Streptococcus as a commensal urogenital tract bacterium and opportunistic pathogen, and explored the role of guaA in bacterial survival and colonization of urine. Analysis of guaA-deficient Streptococcus revealed guanine utilization is essential for bacterial colonization of this niche. The genomic location of guaA in other commensals of the human urogenital tract revealed substantial cross-phyla diversity and organizational structures of guaA that are divergent across phyla. Essentiality of guaA for Streptococcus colonization in the urinary tract establishes that purine biosynthesis is a critical element of the ability of this bacterium to survive and colonize in the host as part of the resident human microbiome.}, }
@article {pmid33649331, year = {2021}, author = {Venskutonytė, R and Koh, A and Stenström, O and Khan, MT and Lundqvist, A and Akke, M and Bäckhed, F and Lindkvist-Petersson, K}, title = {Structural characterization of the microbial enzyme urocanate reductase mediating imidazole propionate production.}, journal = {Nature communications}, volume = {12}, number = {1}, pages = {1347}, pmid = {33649331}, issn = {2041-1723}, mesh = {Arginine/metabolism ; Catalytic Domain ; Flavin-Adenine Dinucleotide/metabolism ; Imidazoles/chemistry/*metabolism ; Kinetics ; Ligands ; Models, Molecular ; Oxidoreductases/chemistry/*metabolism ; Protein Conformation ; Protein Domains ; Shewanella/*enzymology ; Substrate Specificity ; Thermodynamics ; Urocanic Acid/chemistry/*metabolism ; }, abstract = {The human microbiome can produce metabolites that modulate insulin signaling. Type 2 diabetes patients have increased circulating concentrations of the microbially produced histidine metabolite, imidazole propionate (ImP) and administration of ImP in mice resulted in impaired glucose tolerance. Interestingly, the fecal microbiota of the patients had increased capacity to produce ImP, which is mediated by the bacterial enzyme urocanate reductase (UrdA). Here, we describe the X-ray structures of the ligand-binding domains of UrdA in four different states, representing the structural transitions along the catalytic reaction pathway of this unexplored enzyme linked to disease in humans. The structures in combination with functional data provide key insights into the mechanism of action of UrdA that open new possibilities for drug development strategies targeting type 2 diabetes.}, }
@article {pmid33642828, year = {2021}, author = {Reshetnyak, VI and Burmistrov, AI and Maev, IV}, title = {Helicobacter pylori: Commensal, symbiont or pathogen?.}, journal = {World journal of gastroenterology}, volume = {27}, number = {7}, pages = {545-560}, pmid = {33642828}, issn = {2219-2840}, mesh = {Anti-Bacterial Agents/therapeutic use ; *Gastritis, Atrophic/drug therapy ; *Helicobacter Infections/diagnosis/drug therapy ; *Helicobacter pylori ; Humans ; *Peptic Ulcer/drug therapy ; *Stomach Neoplasms/drug therapy ; }, abstract = {This review considers the data on Helicobacter pylori (H. pylori), which have been accumulated over 40 years since its description as an etiological factor in gastrointestinal diseases. The majority of modern publications are devoted to the study of the pathogenic properties of the microorganism in the development of chronic gastritis, peptic ulcer disease, and gastric cancer, as well as methods for its eradication. However, in recent years, there have been more and more studies which have suggested that H. pylori has a beneficial, or potentially positive, effect on the human body. The authors have attempted to objectively analyze the information accumulated in the literature on H. pylori. Some studies consider it as one of the recently identified human bacterial pathogens, and special attention is paid to the evidence suggesting that it is probably part of the composition of the human microbiome as a commensal (commensal from French to English is a table companion) or even a symbiont. The presented data discussing the presence or absence of the effect of H. pylori on human health suggest that there is an apparent ambiguity of the problem. The re-assessment of the data available on H. pylori infection is important in order to answer the question of whether it is necessary to create a program of mass H. pylori eradication or to apply a more personalized approach to treating patients with H. pylori-associated gastrointestinal diseases and to perform eradication therapy.}, }
@article {pmid33637779, year = {2021}, author = {Han, Z and Thuy-Boun, PS and Pfeiffer, W and Vartabedian, VF and Torkamani, A and Teijaro, JR and Wolan, DW}, title = {Identification of an N-acetylneuraminic acid-presenting bacteria isolated from a human microbiome.}, journal = {Scientific reports}, volume = {11}, number = {1}, pages = {4763}, pmid = {33637779}, issn = {2045-2322}, support = {R21 AI139744/AI/NIAID NIH HHS/United States ; UL1 TR002550/TR/NCATS NIH HHS/United States ; }, mesh = {Bacteria/*chemistry/genetics/*isolation &amp; purification/metabolism ; Escherichia coli/chemistry/genetics/isolation &amp; purification/metabolism ; Feces/microbiology ; Genes, Bacterial ; Humans ; *Microbiota ; N-Acetylneuraminic Acid/*analysis/genetics/metabolism ; }, abstract = {N-Acetylneuraminic acid is the most abundant sialic acid (SA) in humans and is expressed as the terminal sugar on intestinal mucus glycans. Several pathogenic bacteria harvest and display host SA on their own surfaces to evade Siglec-mediated host immunity. While previous studies have identified bacterial enzymes associated with SA catabolism, no reported methods permit the selective labeling, tracking, and quantitation of SA-presenting microbes within complex multi-microbial systems. We combined metabolic labeling, click chemistry, 16S rRNA gene, and whole-genome sequencing to track and identify SA-presenting microbes from a cultured human fecal microbiome. We isolated a new strain of Escherichia coli that incorporates SA onto its own surface and encodes for the nanT, neuA, and neuS genes necessary for harvesting and presenting SA. Our method is applicable to the identification of SA-presenting bacteria from human, animal, and environmental microbiomes, as well as providing an entry point for the investigation of surface-expressed SA-associated structures.}, }
@article {pmid33633172, year = {2021}, author = {Carrieri, AP and Haiminen, N and Maudsley-Barton, S and Gardiner, LJ and Murphy, B and Mayes, AE and Paterson, S and Grimshaw, S and Winn, M and Shand, C and Hadjidoukas, P and Rowe, WPM and Hawkins, S and MacGuire-Flanagan, A and Tazzioli, J and Kenny, JG and Parida, L and Hoptroff, M and Pyzer-Knapp, EO}, title = {Explainable AI reveals changes in skin microbiome composition linked to phenotypic differences.}, journal = {Scientific reports}, volume = {11}, number = {1}, pages = {4565}, pmid = {33633172}, issn = {2045-2322}, mesh = {Adult ; Aged ; Female ; Humans ; Middle Aged ; Young Adult ; Aging ; *Artificial Intelligence ; *Biodiversity ; Computational Biology/methods ; Data Analysis ; Deep Learning ; Menopause ; Metagenome ; Metagenomics/methods ; *Microbiota ; *Phenotype ; *Skin/microbiology ; Smokers ; }, abstract = {Alterations in the human microbiome have been observed in a variety of conditions such as asthma, gingivitis, dermatitis and cancer, and much remains to be learned about the links between the microbiome and human health. The fusion of artificial intelligence with rich microbiome datasets can offer an improved understanding of the microbiome's role in human health. To gain actionable insights it is essential to consider both the predictive power and the transparency of the models by providing explanations for the predictions. We combine the collection of leg skin microbiome samples from two healthy cohorts of women with the application of an explainable artificial intelligence (EAI) approach that provides accurate predictions of phenotypes with explanations. The explanations are expressed in terms of variations in the relative abundance of key microbes that drive the predictions. We predict skin hydration, subject's age, pre/post-menopausal status and smoking status from the leg skin microbiome. The changes in microbial composition linked to skin hydration can accelerate the development of personalized treatments for healthy skin, while those associated with age may offer insights into the skin aging process. The leg microbiome signatures associated with smoking and menopausal status are consistent with previous findings from oral/respiratory tract microbiomes and vaginal/gut microbiomes respectively. This suggests that easily accessible microbiome samples could be used to investigate health-related phenotypes, offering potential for non-invasive diagnosis and condition monitoring. Our EAI approach sets the stage for new work focused on understanding the complex relationships between microbial communities and phenotypes. Our approach can be applied to predict any condition from microbiome samples and has the potential to accelerate the development of microbiome-based personalized therapeutics and non-invasive diagnostics.}, }
@article {pmid33622856, year = {2021}, author = {Kleine Bardenhorst, S and Berger, T and Klawonn, F and Vital, M and Karch, A and Rübsamen, N}, title = {Data Analysis Strategies for Microbiome Studies in Human Populations-a Systematic Review of Current Practice.}, journal = {mSystems}, volume = {6}, number = {1}, pages = {}, pmid = {33622856}, issn = {2379-5077}, abstract = {Reproducibility is a major issue in microbiome studies, which is partly caused by missing consensus about data analysis strategies. The complex nature of microbiome data, which are high-dimensional, zero-inflated, and compositional, makes them challenging to analyze, as they often violate assumptions of classic statistical methods. With advances in human microbiome research, research questions and study designs increase in complexity so that more sophisticated data analysis concepts are applied. To improve current practice of the analysis of microbiome studies, it is important to understand what kind of research questions are asked and which tools are used to answer these questions. We conducted a systematic literature review considering all publications focusing on the analysis of human microbiome data from June 2018 to June 2019. Of 1,444 studies screened, 419 fulfilled the inclusion criteria. Information about research questions, study designs, and analysis strategies were extracted. The results confirmed the expected shift to more advanced research questions, as one-third of the studies analyzed clustered data. Although heterogeneity in the methods used was found at any stage of the analysis process, it was largest for differential abundance testing. Especially if the underlying data structure was clustered, we identified a lack of use of methods that appropriately addressed the underlying data structure while taking into account additional dependencies in the data. Our results confirm considerable heterogeneity in analysis strategies among microbiome studies; increasingly complex research questions require better guidance for analysis strategies.IMPORTANCE The human microbiome has emerged as an important factor in the development of health and disease. Growing interest in this topic has led to an increasing number of studies investigating the human microbiome using high-throughput sequencing methods. However, the development of suitable analytical methods for analyzing microbiome data has not kept pace with the rapid progression in the field. It is crucial to understand current practice to identify the scope for development. Our results highlight the need for an extensive evaluation of the strengths and shortcomings of existing methods in order to guide the choice of proper analysis strategies. We have identified where new methods could be designed to address more advanced research questions while taking into account the complex structure of the data.}, }
@article {pmid33608551, year = {2021}, author = {Ho, SX and Min, N and Wong, EPY and Chong, CY and Chu, JJH}, title = {Characterization of oral virome and microbiome revealed distinctive microbiome disruptions in paediatric patients with hand, foot and mouth disease.}, journal = {NPJ biofilms and microbiomes}, volume = {7}, number = {1}, pages = {19}, pmid = {33608551}, issn = {2055-5008}, mesh = {Bacteria/*classification/genetics/isolation &amp; purification ; Case-Control Studies ; Child ; Hand, Foot and Mouth Disease/*microbiology/virology ; High-Throughput Nucleotide Sequencing ; Humans ; Microbiota ; Phylogeny ; RNA, Bacterial/genetics ; RNA, Ribosomal, 16S/genetics ; RNA, Viral/genetics ; Saliva/*microbiology/virology ; Sequence Analysis, RNA/*methods ; Virome ; Viruses/*classification/genetics/isolation &amp; purification ; }, abstract = {While the underlying determinants are unclear, hand, foot and mouth disease (HFMD) presents a wide spectrum of clinical manifestations with varying severity in different individuals. Recently, many studies identified the human microbiome as a critical factor in the pathogenesis of various diseases. Therefore, we here investigated the ecological dynamics of the oral microbiome changes during the HFMD infection. After targeted enrichment of all known vertebrate viruses, the virome profiles of symptomatic and asymptomatic HFMD patients were examined and revealed to be significantly altered from those of healthy individuals, with nine discriminative viruses detected. Further characterization of the prokaryotic microbiome revealed an elevated level of Streptococcus sp. as the most important signature of the symptomatic HFMD cohort, positively correlating to the level of enterovirus A RNA. In addition, we found that while coxsackievirus A5 is detected in saliva RNA of all asymptomatic cases, coxsackievirus A6 dominates the majority of the symptomatic cohort.}, }
@article {pmid33606675, year = {2021}, author = {Coyte, KZ and Rao, C and Rakoff-Nahoum, S and Foster, KR}, title = {Ecological rules for the assembly of microbiome communities.}, journal = {PLoS biology}, volume = {19}, number = {2}, pages = {e3001116}, pmid = {33606675}, issn = {1545-7885}, support = {/WT_/Wellcome Trust/United Kingdom ; DP2 GM136652/GM/NIGMS NIH HHS/United States ; K08 AI130392/AI/NIAID NIH HHS/United States ; P30 DK040561/DK/NIDDK NIH HHS/United States ; 201341/A/16/Z/WT_/Wellcome Trust/United Kingdom ; 209397/Z/17/Z/WT_/Wellcome Trust/United Kingdom ; }, mesh = {Humans ; Infant, Newborn ; *Infant, Premature ; *Microbiota ; Milk, Human/microbiology ; Models, Theoretical ; Symbiosis ; }, abstract = {Humans and many other hosts establish a diverse community of beneficial microbes anew each generation. The order and identity of incoming symbionts is critical for health, but what determines the success of the assembly process remains poorly understood. Here we develop ecological theory to identify factors important for microbial community assembly. Our method maps out all feasible pathways for the assembly of a given microbiome-with analogies to the mutational maps underlying fitness landscapes in evolutionary biology. Building these "assembly maps" reveals a tradeoff at the heart of the assembly process. Ecological dependencies between members of the microbiota make assembly predictable-and can provide metabolic benefits to the host-but these dependencies may also create barriers to assembly. This effect occurs because interdependent species can fail to establish when each relies on the other to colonize first. We support our predictions with published data from the assembly of the preterm infant microbiota, where we find that ecological dependence is associated with a predictable order of arrival. Our models also suggest that hosts can overcome barriers to assembly via mechanisms that either promote the uptake of multiple symbiont species in one step or feed early colonizers. This predicted importance of host feeding is supported by published data on the impacts of breast milk in the assembly of the human microbiome. We conclude that both microbe to microbe and host to microbe interactions are important for the trajectory of microbiome assembly.}, }
@article {pmid33606255, year = {2021}, author = {Joseph, TA and Pe'er, I}, title = {An Introduction to Whole-Metagenome Shotgun Sequencing Studies.}, journal = {Methods in molecular biology (Clifton, N.J.)}, volume = {2243}, number = {}, pages = {107-122}, pmid = {33606255}, issn = {1940-6029}, mesh = {Archaea/genetics ; Bacteria/genetics ; Humans ; Metagenome/*genetics ; Metagenomics/methods ; Microbiota/*genetics ; Sequence Analysis, DNA/methods ; Viruses/genetics ; }, abstract = {Microbial communities are found across diverse environments, including within and across the human body. As many microbes are unculturable in the lab, much of what is known about a microbiome-a collection of bacteria, fungi, archaea, and viruses inhabiting an environment--is from the sequencing of DNA from within the constituent community. Here, we provide an introduction to whole-metagenome shotgun sequencing studies, a ubiquitous approach for characterizing microbial communities, by reviewing three major research areas in metagenomics: assembly, community profiling, and functional profiling. Though not exhaustive, these areas encompass a large component of the metagenomics literature. We discuss each area in depth, the challenges posed by whole-metagenome shotgun sequencing, and approaches fundamental to the solutions of each. We conclude by discussing promising areas for future research. Though our emphasis is on the human microbiome, the methods discussed are broadly applicable across study systems.}, }
@article {pmid33603805, year = {2020}, author = {Brandão, P and Gonçalves-Henriques, M}, title = {The Impact of Female Genital Microbiota on Fertility and Assisted Reproductive Treatments.}, journal = {Journal of family &amp; reproductive health}, volume = {14}, number = {3}, pages = {131-149}, pmid = {33603805}, issn = {1735-8949}, abstract = {Objective: To review publish data about human microbiome. It is known to modulate many body functions. In the field of Reproductive Medicine, the main question is in what extent may female genital tract microbiome influence fertility, both by spontaneous conception or after Assisted Reproductive Treatments (ART). The aim of this work is to review publish data about this matter. Materials and methods: This is a systematic review on the effect of the microbiota of the female genital tract on human fertility and on the outcomes of ART. Results: Fourteen articles were retrieved, concerning female lower genital tract and endometrium microbiota, including 5 case-controls studies about its impact on fertility, 8 cohort studies regarding ART outcomes and 1 mixed study. The main variables considered were richness and diversity of species, Lactobacillus dominance and the role of other bacteria. Results and conclusions of the various studies were quite diverse and incoherent. Despite the inconsistency of the studies, it seems that vaginal, cervical and endometrial microbiome may eventually play a role. Whether high richness and diversity of species, low amounts of Lactobacillus spp. or the presence of other bacteria, such as Gardnerella spp., may adversely affect reproductive outcomes is not clear. Conclusion: The influence of female genital microbiota on the ability to conceive is still unclear, due to the paucity and inconsistency of published data.}, }
@article {pmid33600401, year = {2021}, author = {Goldberg, Y and Friedman, J}, title = {Positive interactions within and between populations decrease the likelihood of evolutionary rescue.}, journal = {PLoS computational biology}, volume = {17}, number = {2}, pages = {e1008732}, pmid = {33600401}, issn = {1553-7358}, mesh = {*Adaptation, Physiological ; Animals ; *Biological Evolution ; Computational Biology ; Computer Simulation ; *Ecosystem ; Extinction, Biological ; Humans ; *Models, Biological ; Phenotype ; Probability ; Selection, Genetic ; Stress, Physiological ; *Symbiosis ; }, abstract = {Positive interactions, including intraspecies cooperation and interspecies mutualisms, play crucial roles in shaping the structure and function of many ecosystems, ranging from plant communities to the human microbiome. While the evolutionary forces that form and maintain positive interactions have been investigated extensively, the influence of positive interactions on the ability of species to adapt to new environments is still poorly understood. Here, we use numerical simulations and theoretical analyses to study how positive interactions impact the likelihood that populations survive after an environment deteriorates, such that survival in the new environment requires quick adaptation via the rise of new mutants-a scenario known as evolutionary rescue. We find that the probability of evolutionary rescue in populations engaged in positive interactions is reduced significantly. In cooperating populations, this reduction is largely due to the fact that survival may require at least a minimal number of individuals, meaning that adapted mutants must arise and spread before the population declines below this threshold. In mutualistic populations, the rescue probability is decreased further due to two additional effects-the need for both mutualistic partners to adapt to the new environment, and competition between the two species. Finally, we show that the presence of cheaters reduces the likelihood of evolutionary rescue even further, making it extremely unlikely. These results indicate that while positive interactions may be beneficial in stable environments, they can hinder adaptation to changing environments and thereby elevate the risk of population collapse. Furthermore, these results may hint at the selective pressures that drove co-dependent unicellular species to form more adaptable organisms able to differentiate into multiple phenotypes, including multicellular life.}, }
@article {pmid33600151, year = {2021}, author = {Brimberry, M and Toma, MA and Hines, KM and Lanzilotta, WN}, title = {HutW from Vibrio cholerae Is an Anaerobic Heme-Degrading Enzyme with Unique Functional Properties.}, journal = {Biochemistry}, volume = {60}, number = {9}, pages = {699-710}, pmid = {33600151}, issn = {1520-4995}, support = {R01 GM124203/GM/NIGMS NIH HHS/United States ; }, mesh = {Anaerobiosis ; Bacterial Outer Membrane Proteins/chemistry/*metabolism ; Gene Expression Regulation, Bacterial ; Heme/*metabolism ; Methyltransferases/chemistry/*metabolism ; NADP/*metabolism ; Protein Conformation ; S-Adenosylmethionine/metabolism ; Tetrapyrroles/*chemistry ; Vibrio cholerae/*enzymology ; }, abstract = {Increasing antibiotic resistance, and a growing recognition of the importance of the human microbiome, demand that new therapeutic targets be identified. Characterization of metabolic pathways that are unique to enteric pathogens represents a promising approach. Iron is often the rate-limiting factor for growth, and Vibrio cholerae, the causative agent of cholera, has been shown to contain numerous genes that function in the acquisition of iron from the environment. Included in this arsenal of genes are operons dedicated to obtaining iron from heme and heme-containing proteins. Given the persistence of cholera, an important outstanding question is whether V. cholerae is capable of anaerobic heme degradation as was recently reported for enterohemorrhagic Escherichia coli O157:H7. In this work, we demonstrate that HutW from V. cholerae is a radical S-adenosylmethionine methyl transferase involved in the anaerobic opening of the porphyrin ring of heme. However, in contrast to the enzyme ChuW, found in enterohemorrhagic E. coli O157:H7, there are notable differences in the mechanism and products of the HutW reaction. Of particular interest are data that demonstrate HutW will catalyze ring opening as well as tetrapyrrole reduction and can utilize reduced nicotinamide adenine dinucleotide phosphate as an electron source. The biochemical and biophysical properties of HutW are presented, and the evolutionary implications are discussed.}, }
@article {pmid33598417, year = {2020}, author = {Bendriss, G and Al-Ali, D and Shafiq, A and Laswi, I and Mhaimeed, N and Salameh, M and Burney, Z and Pillai, K and Chaari, A and Zakaria, D and Yousri, NA}, title = {Targeting the gut microbiome: A brief report on the awareness, practice, and readiness to engage in clinical interventions in Qatar.}, journal = {Qatar medical journal}, volume = {2020}, number = {3}, pages = {47}, pmid = {33598417}, issn = {0253-8253}, abstract = {BACKGROUND: There has been a growing global interest in the role of gut microbiota in the pathogenesis of diseases and the potentials of targeting the microbiome in clinical interventions. Very few clinical studies in Qatar focused on gut microbiome. This study aimed to assess the awareness of healthcare professionals, scientists, and the general public on the role of gut microbiota in health and diseases and, more specifically, in disorders of the gut-brain axis such as neurodevelopmental disorders (NDDs) or gastrointestinal (GI) disorders. It also aimed to evaluate the readiness of the population to engage in clinical trials involving dietary interventions or fecal transplants.<br><br>METHODS: A total of 156 participants were recruited to answer questionnaires-from healthcare professionals and scientists (HSs; n&#xa0;=&#xa0;44) and the general public (n&#xa0;=&#xa0;112). Participants from the general public self-reported their diagnosis of NDDs-autism or attention deficit hyperactivity disorder (n&#xa0;=&#xa0;36)-or GI diseases or disorders (n&#xa0;=&#xa0;18) or as having none of them (n&#xa0;=&#xa0;58). Two questionnaires for HSs and for the general public were distributed, and basic descriptive and statistical analyses were conducted using the Fisher's exact test.<br><br>RESULTS: Among the participating HSs, 95% admitted that they had minimum to no knowledge on the role of gut microbes in health and diseases, and only 15.9% felt that their peers were knowledgeable about it. Nevertheless, 97.7% of HSs thought that gut microbiota should be considered when devising treatment plans as 79.1% believed that gut dysbiosis is involved in the pathogenesis of diseases. For the general public, 54% stated that they have read about studies on the potential benefits of microbes in the prevention, treatment, and management of diseases, with a higher proportion of them belonging to the GI group (p&#xa0;=&#xa0;0.0523). The GI group was also more aware of the existence of the use of fecal transplants for treating their condition (p&#xa0;=&#xa0;0.01935). Awareness was also reflected in participants' attempts to engage in dietary changes, as 40% tried a dietary intervention, which has noticeably changed their or their child's symptoms. This study reported a highly significant association between being exposed to multiple antibiotic courses before three years of age and being part of the NDD group (p&#xa0;=&#xa0;0.0003). Public readiness to engage in interventions that target the gut microbiome, such as intensive dietary interventions or even fecal transplants, was perceived by HSs to be lower than what was stated by the public, with 87.96% of public being ready to engage in intensive dietary interventions and 66.98% in fecal transplants.<br><br>CONCLUSION: The study revealed that the role of gut microbes in health and diseases, and especially through the gut-brain axis, is still unclear in both the scientific community and general public. While acknowledging the importance of gut microbes, the lack of information regarding the link between lifestyle and gut microbes is considered to hold the public in the precontemplation/contemplation stages of the transtheoretical model of behavioral change. An interdisciplinary approach to new knowledge produced by microbiome studies is needed to run awareness campaigns and continue professional development activities on the benefits of lifestyle-based modulation of gut microbiome, thus engaging the general public in lifestyle changes and facilitating clinical research in human microbiome investigations in Qatar.}, }
@article {pmid33594458, year = {2021}, author = {Yao, T and Wang, Z and Liang, X and Liu, C and Yu, Z and Han, X and Liu, R and Liu, Y and Liu, C and Chen, L}, title = {Signatures of vaginal microbiota by 16S rRNA gene: potential bio-geographical application in Chinese Han from three regions of China.}, journal = {International journal of legal medicine}, volume = {135}, number = {4}, pages = {1213-1224}, pmid = {33594458}, issn = {1437-1596}, support = {2020A1515010938//the Natural Science Foundation of Guangdong Province/ ; 2019030016//the Science and Technology Program of Guangzhou, China/ ; KF1914//the Opening Fund of Shanghai Key Laboratory of Forensic Medicine (Institute of Forensic Science, Ministry of Justice, China)/ ; }, mesh = {Algorithms ; Asian People/genetics ; Bacteria/classification/isolation &amp; purification ; Biomarkers ; Female ; *Genes, rRNA ; High-Throughput Nucleotide Sequencing ; Humans ; *Microbiota ; RNA, Ribosomal, 16S/*genetics ; Sequence Analysis, RNA ; Vagina/*microbiology ; }, abstract = {The human microbiome is expected to be a new and promising tool for classification of human epithelial materials. Vaginal fluids are one of the most common biological samples in forensic sexual assault cases, and its identification is crucial to accurately determine the nature of the case. With the development of molecular biology technologies, the concept of vaginal microflora in different physiological states, ethnic groups, and geography is constantly improved. In this study, we conducted high-throughput sequencing of the V3-V4 hypervariable regions of the 16S rRNA gene in vaginal samples from Henan, Guangdong, and Xinjiang populations, in an attempt to reveal more information about the vaginal microflora in different regions. The results showed that the bio-geographical factors might affect the relative abundance of some vaginal microflora, but there was no significant difference in the composition of dominant bacteria in the vagina, which was mainly composed of Lactobacillus and Gardnerella. However, prediction models based on the random forest algorithm suggested that we might be able to distinguish vaginal fluids from populations of different regions according to the species-level OTUs in low abundance. It is promising that microbiome-based methods could provide more personal information when being attempted to trace the origin of body fluids.}, }
@article {pmid33585285, year = {2020}, author = {Stavropoulou, E and Kantartzi, K and Tsigalou, C and Konstantinidis, T and Voidarou, C and Konstantinidis, T and Bezirtzoglou, E}, title = {Unraveling the Interconnection Patterns Across Lung Microbiome, Respiratory Diseases, and COVID-19.}, journal = {Frontiers in cellular and infection microbiology}, volume = {10}, number = {}, pages = {619075}, pmid = {33585285}, issn = {2235-2988}, mesh = {Bacteria/classification/*isolation &amp; purification ; COVID-19/pathology ; Gastrointestinal Tract/microbiology ; Humans ; Lung/*immunology/*microbiology ; Microbiota/*physiology ; SARS-CoV-2/growth &amp; development ; }, abstract = {Albeit the lungs were thought to be sterile, recent scientific data reported a microbial microbiota in the lungs of healthy individuals. Apparently, new developments in technological approachesincluding genome sequencing methodologies contributed in the identification of the microbiota and shed light on the role of the gut and lung microbiomes in the development of respiratory diseases. Moreover, knowledge of the human microbiome in health may act as a tool for evaluating characteristic shifts in the case of disease. This review paper discusses the development of respiratory disease linked to the intestinal dysbiosis which influences the lung immunity and microbiome. The gastrointestinal-lung dialogue provides interesting aspects in the pathogenesis of the respiratory diseases. Lastly, we were further interested on the role of this interconnection in the progression and physiopathology of newly emergedCOVID-19.}, }
@article {pmid33583541, year = {2021}, author = {Shafaei, A and Rees, J and Christophersen, CT and Devine, A and Broadhurst, D and Boyce, MC}, title = {Extraction and quantitative determination of bile acids in feces.}, journal = {Analytica chimica acta}, volume = {1150}, number = {}, pages = {338224}, doi = {10.1016/j.aca.2021.338224}, pmid = {33583541}, issn = {1873-4324}, mesh = {*Bile Acids and Salts ; Chromatography, High Pressure Liquid ; Chromatography, Liquid ; Feces ; Humans ; Reference Standards ; Reproducibility of Results ; *Tandem Mass Spectrometry ; }, abstract = {With rapid advances in gut microbiome research, fecal bile acids are increasingly being monitored as potential biomarkers of diet related disease susceptibility. As such, rapid, robust and reliable methods for their analysis are of increasing importance. Herein is described a simple extraction method for the analysis of bile acids in feces suitable for subsequent quantification by liquid chromatography and tandem mass spectrometry. A C18 column separated the analytes with excellent peak shape and retention time repeatability maintained across 800 injections. The intra-day and inter-day precision and accuracy was greater than 80%. Recoveries ranged from 83.58 to 122.41%. The limit of detection and limit of quantification were in the range 2.5-15 nM, respectively. The optimized method involved extracting bile acids from wet feces with minimal clean up. A second aliquot of fecal material was dried and weighed to correct for water content. Extracting from dried feces showed reduced recovery that could be corrected for by spiking the feces with deuterated standards prior to drying. Storage of the extracts and standards in a refrigerated autosampler prior to analysis on the LC-MS is necessary. Multiple freeze-thaws of both extracts and standards lead to poor recoveries for some bile acids. The method was successfully applied to 100 human fecal samples.}, }
@article {pmid33583306, year = {2021}, author = {Maslennikov, R and Poluektova, E and Ivashkin, V and Svistunov, A}, title = {Diarrhoea in adults with coronavirus disease-beyond incidence and mortality: a systematic review and meta-analysis.}, journal = {Infectious diseases (London, England)}, volume = {53}, number = {5}, pages = {348-360}, doi = {10.1080/23744235.2021.1885733}, pmid = {33583306}, issn = {2374-4243}, mesh = {Adult ; COVID-19/*epidemiology ; Diarrhea/*epidemiology ; Humans ; Incidence ; }, abstract = {AIM: Diarrhoea is a relatively common manifestation of coronavirus disease (COVID-19), but there is no systematic review which comprehensively describes it beyond its incidence and impact on prognosis. This study aims to provide a detailed systematic review of diarrhoea in adults with COVID-19.<br><br>METHODS: A PUBMED and Scopus search (until 7 September 2020) was performed. Studies that were limited to describing incidence of diarrhoea and its effect on prognosis were excluded.<br><br>RESULTS: Twenty-six papers including 7860 patients with COVID-19 were subjected to synthesis. Mean duration of diarrhoea was 4.2 (3.6-4.9) days (range 1-16&#x2009;days), whereas mean bowel movement count was 4.6 (3.8-5.3) and maximum was 20 per day. Diarrhoea started on an average 5.1 (3.8-6.5) days after disease onset but was the first manifestation in 4.3% patients. Stool occult blood was detected in 6.8% of patients with diarrhoea, while 53.3% cases had watery diarrhoea. Patients with diarrhoea also had elevated faecal calprotectin. Viral genome in faeces was detected more often in patients with diarrhoea and most often in patients without respiratory symptoms. Fever, myalgia and respiratory symptoms were observed with the same incidence in patients with and without diarrhoea. Similarly, there were no differences noted in complete blood count and most inflammation biomarkers between patients with and without diarrhoea. However, nausea, vomiting abdominal pain, sneezing and headache were more common in patients with diarrhoea. Diarrhoea was the main manifestation of COVID-19 in 6.1% of cases and this form of the disease had specific features.<br><br>CONCLUSIONS: Diarrhoea in COVID-19 needs further investigation.}, }
@article {pmid33580619, year = {2021}, author = {Mousavi-Derazmahalleh, M and Stott, A and Lines, R and Peverley, G and Nester, G and Simpson, T and Zawierta, M and De La Pierre, M and Bunce, M and Christophersen, CT}, title = {eDNAFlow, an automated, reproducible and scalable workflow for analysis of environmental DNA sequences exploiting Nextflow and Singularity.}, journal = {Molecular ecology resources}, volume = {21}, number = {5}, pages = {1697-1704}, doi = {10.1111/1755-0998.13356}, pmid = {33580619}, issn = {1755-0998}, mesh = {*Computational Biology ; *DNA Barcoding, Taxonomic ; *DNA, Environmental ; Reproducibility of Results ; Software ; Workflow ; }, abstract = {Metabarcoding of environmental DNA (eDNA) when coupled with high throughput sequencing is revolutionising the way biodiversity can be monitored across a wide range of applications. However, the large number of tools deployed in downstream bioinformatic analyses often places a challenge in configuration and maintenance of a workflow, and consequently limits the research reproducibility. Furthermore, scalability needs to be considered to handle the growing amount of data due to increase in sequence output and the scale of project. Here, we describe eDNAFlow, a fully automated workflow that employs a number of state-of-the-art applications to process eDNA data from raw sequences (single-end or paired-end) to generation of curated and noncurated zero-radius operational taxonomic units (ZOTUs) and their abundance tables. This pipeline is based on Nextflow and Singularity which enable a scalable, portable and reproducible workflow using software containers on a local computer, clouds and high-performance computing (HPC) clusters. Finally, we present an in-house Python script to assign taxonomy to ZOTUs based on user specified thresholds for assigning lowest common ancestor (LCA). We demonstrate the utility and efficiency of the pipeline using an example of a published coral diversity biomonitoring study. Our results were congruent with the aforementioned study. The scalability of the pipeline is also demonstrated through analysis of a large data set containing 154 samples. To our knowledge, this is the first automated bioinformatic pipeline for eDNA analysis using two powerful tools: Nextflow and Singularity. This pipeline addresses two major challenges in the analysis of eDNA data; scalability and reproducibility.}, }
@article {pmid33579330, year = {2021}, author = {Schwartz, DJ and Langdon, AE and Dantas, G}, title = {Correction to: Understanding the impact of antibiotic perturbation on the human microbiome.}, journal = {Genome medicine}, volume = {13}, number = {1}, pages = {26}, pmid = {33579330}, issn = {1756-994X}, }
@article {pmid33571456, year = {2021}, author = {Ianiro, G and Mullish, BH and Hvas, CL and Segal, JP and Kuijper, EJ and Costello, SP and Kelly, CR and Allegretti, JR and Fischer, M and Iqbal, TH and Satokari, R and Kao, D and van Prehn, J and Ng, SC and Bibbò, S and Baunwall, SMD and Quraishi, MN and Sokol, H and Zhang, F and Keller, J and Masucci, L and Quaranta, G and Kassam, Z and Sanguinetti, M and Tilg, H and Gasbarrini, A and Cammarota, G}, title = {SARS-CoV-2 vaccines and donor recruitment for FMT.}, journal = {The lancet. Gastroenterology &amp; hepatology}, volume = {6}, number = {4}, pages = {264-266}, pmid = {33571456}, issn = {2468-1253}, mesh = {COVID-19/*prevention &amp; control/transmission ; *COVID-19 Vaccines ; Donor Selection/*organization &amp; administration ; *Fecal Microbiota Transplantation ; Humans ; }, }
@article {pmid33562104, year = {2021}, author = {Mennini, M and Reddel, S and Del Chierico, F and Gardini, S and Quagliariello, A and Vernocchi, P and Valluzzi, RL and Fierro, V and Riccardi, C and Napolitano, T and Fiocchi, AG and Putignani, L}, title = {Gut Microbiota Profile in Children with IgE-Mediated Cow's Milk Allergy and Cow's Milk Sensitization and Probiotic Intestinal Persistence Evaluation.}, journal = {International journal of molecular sciences}, volume = {22}, number = {4}, pages = {}, pmid = {33562104}, issn = {1422-0067}, support = {201587X003556//Italian Ministry of Health Ricerca Corrente/ ; }, mesh = {Animals ; Bifidobacterium/*metabolism ; Bifidobacterium breve/*metabolism ; Bifidobacterium longum subspecies infantis/*metabolism ; Breast Feeding ; Child, Preschool ; Dysbiosis/microbiology ; Female ; Gastrointestinal Microbiome/*physiology ; Humans ; Immunoglobulin E/immunology ; Infant ; Male ; Milk/immunology ; Milk Hypersensitivity/microbiology/*therapy ; Probiotics/*therapeutic use ; }, abstract = {Food allergy (FA) and, in particular, IgE-mediated cow's milk allergy is associated with compositional and functional changes of gut microbiota. In this study, we compared the gut microbiota of cow's milk allergic (CMA) infants with that of cow's milk sensitized (CMS) infants and Healthy controls. The effect of the intake of a mixture of Bifidobacterium longum subsp. longum BB536, Bifidobacterium breve M-16V and Bifidobacterium longum subsp. infantis M-63 on gut microbiota modulation of CMA infants and probiotic persistence was also investigated. Gut microbiota of CMA infants resulted to be characterized by a dysbiotic status with a prevalence of some bacteria as Haemophilus, Klebsiella, Prevotella, Actinobacillus and Streptococcus. Among the three strains administered, B.longum subsp. infantis colonized the gastrointestinal tract and persisted in the gut microbiota of infants with CMA for 60 days. This colonization was associated with perturbations of the gut microbiota, specifically with the increase of Akkermansia and Ruminococcus. Multi-strain probiotic formulations can be studied for their persistence in the intestine by monitoring specific bacterial probes persistence and exploiting microbiota profiling modulation before the evaluation of their therapeutic effects.}, }
@article {pmid33552122, year = {2020}, author = {Deek, RA and Li, H}, title = {A Zero-Inflated Latent Dirichlet Allocation Model for Microbiome Studies.}, journal = {Frontiers in genetics}, volume = {11}, number = {}, pages = {602594}, pmid = {33552122}, issn = {1664-8021}, support = {R01 GM123056/GM/NIGMS NIH HHS/United States ; R01 GM129781/GM/NIGMS NIH HHS/United States ; }, abstract = {The human microbiome consists of a community of microbes in varying abundances and is shown to be associated with many diseases. An important first step in many microbiome studies is to identify possible distinct microbial communities in a given data set and to identify the important bacterial taxa that characterize these communities. The data from typical microbiome studies are high dimensional count data with excessive zeros due to both absence of species (structural zeros) and low sequencing depth or dropout. Although methods have been developed for identifying the microbial communities based on mixture models of counts, these methods do not account for excessive zeros observed in the data and do not differentiate structural from sampling zeros. In this paper, we introduce a zero-inflated Latent Dirichlet Allocation model (zinLDA) for sparse count data observed in microbiome studies. zinLDA builds on the flexible Latent Dirichlet Allocation model and allows for zero inflation in observed counts. We develop an efficient Markov chain Monte Carlo (MCMC) sampling procedure to fit the model. Results from our simulations show zinLDA provides better fits to the data and is able to separate structural zeros from sampling zeros. We apply zinLDA to the data set from the American Gut Project and identify microbial communities characterized by different bacterial genera.}, }
@article {pmid33550293, year = {2021}, author = {Zisimopoulos, A and Klavdianou, O and Theodossiadis, P and Chatziralli, I}, title = {The Role of the Microbiome in Age-Related Macular Degeneration: A Review of the Literature.}, journal = {Ophthalmologica. Journal international d'ophtalmologie. International journal of ophthalmology. Zeitschrift fur Augenheilkunde}, volume = {244}, number = {3}, pages = {173-178}, doi = {10.1159/000515026}, pmid = {33550293}, issn = {1423-0267}, mesh = {Aged ; Biomarkers ; Humans ; *Macular Degeneration/diagnosis ; *Microbiota ; }, abstract = {BACKGROUND: Age-related macular degeneration (AMD) is a progressive, multifactorial, degenerative disease and the leading cause of severe visual loss in the elderly population. The exact pathogenesis of AMD remains elusive, being the combination of genetic, environmental, metabolic, and functional processes. A better understanding of the disease's pathophysiology can lead to new treatment targets. The human microbiome seems to be a potential therapeutic pathway for AMD, as it has been recently proven to play a role in its pathogenesis.<br><br>SUMMARY: This review sheds light on the association between the microbiome and AMD. Key Messages: The current evidence based on the existing literature shows that there are differences in taxonomical and functional profiles in the human microbiome between patients with AMD and controls, suggesting that the microbiome is implicated in AMD onset and progression, being a link between AMD and nutrition/diet. Additionally, specific bacterial classes have been proposed as potential biomarkers for AMD diagnosis. Further randomized clinical studies with a large sample are needed to elucidate the role of the microbiome in AMD and to draw more solid conclusions.}, }
@article {pmid33544117, year = {2021}, author = {Moysidou, CM and Owens, RM}, title = {Advances in modelling the human microbiome-gut-brain axis in vitro.}, journal = {Biochemical Society transactions}, volume = {49}, number = {1}, pages = {187-201}, pmid = {33544117}, issn = {1470-8752}, mesh = {Animals ; Bioengineering/methods/trends ; Brain-Gut Axis/*physiology ; Cells, Cultured ; Gastrointestinal Microbiome/physiology ; Humans ; Mice ; Microbiota/*physiology ; Models, Biological ; Organoids ; Tissue Culture Techniques/methods/*trends ; }, abstract = {The human gut microbiome has emerged as a key player in the bidirectional communication of the gut-brain axis, affecting various aspects of homeostasis and pathophysiology. Until recently, the majority of studies that seek to explore the mechanisms underlying the microbiome-gut-brain axis cross-talk, relied almost exclusively on animal models, and particularly gnotobiotic mice. Despite the great progress made with these models, various limitations, including ethical considerations and interspecies differences that limit the translatability of data to human systems, pushed researchers to seek for alternatives. Over the past decades, the field of in vitro modelling of tissues has experienced tremendous growth, thanks to advances in 3D cell biology, materials, science and bioengineering, pushing further the borders of our ability to more faithfully emulate the in vivo situation. The discovery of stem cells has offered a new source of cells, while their use in generating gastrointestinal and brain organoids, among other tissues, has enabled the development of novel 3D tissues that better mimic the native tissue structure and function, compared with traditional assays. In parallel, organs-on-chips technology and bioengineered tissues have emerged as highly promising alternatives to animal models for a wide range of applications. Here, we discuss how recent advances and trends in this area can be applied in host-microbe and host-pathogen interaction studies. In addition, we highlight paradigm shifts in engineering more robust human microbiome-gut-brain axis models and their potential to expand our understanding of this complex system and hence explore novel, microbiome-based therapeutic approaches.}, }
@article {pmid33543271, year = {2021}, author = {Rong, R and Jiang, S and Xu, L and Xiao, G and Xie, Y and Liu, DJ and Li, Q and Zhan, X}, title = {MB-GAN: Microbiome Simulation via Generative Adversarial Network.}, journal = {GigaScience}, volume = {10}, number = {2}, pages = {}, pmid = {33543271}, issn = {2047-217X}, support = {R56 HG011035/HG/NHGRI NIH HHS/United States ; R01 GM126479/GM/NIGMS NIH HHS/United States ; R01 HG008983/HG/NHGRI NIH HHS/United States ; P30 CA142543/CA/NCI NIH HHS/United States ; }, mesh = {Computer Simulation ; Humans ; Image Processing, Computer-Assisted ; *Microbiota ; *Neural Networks, Computer ; Proteins ; }, abstract = {BACKGROUND: Trillions of microbes inhabit the human body and have a profound effect on human health. The recent development of metagenome-wide association studies and other quantitative analysis methods accelerate the discovery of the associations between human microbiome and diseases. To assess the strengths and limitations of these analytical tools, simulating realistic microbiome datasets is critically important. However, simulating the real microbiome data is challenging because it is difficult to model their correlation structure using explicit statistical models.<br><br>RESULTS: To address the challenge of simulating realistic microbiome data, we designed a novel simulation framework termed MB-GAN, by using a generative adversarial network (GAN) and utilizing methodology advancements from the deep learning community. MB-GAN can automatically learn from given microbial abundances and compute simulated abundances that are indistinguishable from them. In practice, MB-GAN showed the following advantages. First, MB-GAN avoids explicit statistical modeling assumptions, and it only requires real datasets as inputs. Second, unlike the traditional GANs, MB-GAN is easily applicable and can converge efficiently.<br><br>CONCLUSIONS: By applying MB-GAN to a case-control gut microbiome study of 396 samples, we demonstrated that the simulated data and the original data had similar first-order and second-order properties, including sparsity, diversities, and taxa-taxa correlations. These advantages are suitable for further microbiome methodology development where high-fidelity microbiome data are needed.}, }
@article {pmid33541264, year = {2021}, author = {Abe, K and Hirayama, M and Ohno, K and Shimamura, T}, title = {Hierarchical non-negative matrix factorization using clinical information for microbial communities.}, journal = {BMC genomics}, volume = {22}, number = {1}, pages = {104}, pmid = {33541264}, issn = {1471-2164}, support = {19H05210//Japan Society for the Promotion of Science (JP)/ ; 20H04281//Japan Society for the Promotion of Science/ ; 20H04841//Japan Society for the Promotion of Science/ ; 20K21832//Japan Society for the Promotion of Science/ ; 20K19921//Japan Society for the Promotion of Science/ ; JP20dm0107087h0005//Japan Agency for Medical Research and Development/ ; JP20ek0109488h0001//Japan Agency for Medical Research and Development/ ; JP20km0405207h9905//Japan Agency for Medical Research and Development/ ; JP20gm1010002h0005//Japan Agency for Medical Research and Development/ ; }, mesh = {*Algorithms ; Bayes Theorem ; Computer Simulation ; Humans ; Metagenome ; Metagenomics ; *Microbiota ; }, abstract = {BACKGROUND: The human microbiome forms very complex communities that consist of hundreds to thousands of different microorganisms that not only affect the host, but also participate in disease processes. Several state-of-the-art methods have been proposed for learning the structure of microbial communities and to investigate the relationship between microorganisms and host environmental factors. However, these methods were mainly designed to model and analyze single microbial communities that do not interact with or depend on other communities. Such methods therefore cannot comprehend the properties between interdependent systems in communities that affect host behavior and disease processes.<br><br>RESULTS: We introduce a novel hierarchical Bayesian framework, called BALSAMICO (BAyesian Latent Semantic Analysis of MIcrobial COmmunities), which uses microbial metagenome data to discover the underlying microbial community structures and the associations between microbiota and their environmental factors. BALSAMICO models mixtures of communities in the framework of nonnegative matrix factorization, taking into account environmental factors. We proposes an efficient procedure for estimating parameters. A simulation then evaluates the accuracy of the estimated parameters. Finally, the method is used to analyze clinical data. In this analysis, we successfully detected bacteria related to colorectal cancer.<br><br>CONCLUSIONS: These results show that the method not only accurately estimates the parameters needed to analyze the connections between communities of microbiota and their environments, but also allows for the effective detection of these communities in real-world circumstances.}, }
@article {pmid33540903, year = {2021}, author = {Nalbantoglu, OU}, title = {Information Theoretic Metagenome Assembly Allows the Discovery of Disease Biomarkers in Human Microbiome.}, journal = {Entropy (Basel, Switzerland)}, volume = {23}, number = {2}, pages = {}, pmid = {33540903}, issn = {1099-4300}, support = {120E092//T&#xfc;rkiye Bilimsel ve Teknolojik Ara&#x15f;tirma Kurumu/ ; }, abstract = {Quantitative metagenomics is an important field that has delivered successful microbiome biomarkers associated with host phenotypes. The current convention mainly depends on unsupervised assembly of metagenomic contigs with a possibility of leaving interesting genetic material unassembled. Additionally, biomarkers are commonly defined on the differential relative abundance of compositional or functional units. Accumulating evidence supports that microbial genetic variations are as important as the differential abundance content, implying the need for novel methods accounting for the genetic variations in metagenomics studies. We propose an information theoretic metagenome assembly algorithm, discovering genomic fragments with maximal self-information, defined by the empirical distributions of nucleotides across the phenotypes and quantified with the help of statistical tests. Our algorithm infers fragments populating the most informative genetic variants in a single contig, named supervariant fragments. Experiments on simulated metagenomes, as well as on a colorectal cancer and an atherosclerotic cardiovascular disease dataset consistently discovered sequences strongly associated with the disease phenotypes. Moreover, the discriminatory power of these putative biomarkers was mainly attributed to the genetic variations rather than relative abundance. Our results support that a focus on metagenomics methods considering microbiome population genetics might be useful in discovering disease biomarkers with a great potential of translating to molecular diagnostics and biotherapeutics applications.}, }
@article {pmid33538570, year = {2021}, author = {Haque, A and Woolery-Lloyd, H}, title = {Inflammaging in Dermatology: A New Frontier for Research.}, journal = {Journal of drugs in dermatology : JDD}, volume = {20}, number = {2}, pages = {144-149}, doi = {10.36849/JDD.5481}, pmid = {33538570}, issn = {1545-9616}, mesh = {Aging/*immunology ; Anti-Inflammatory Agents/pharmacology/therapeutic use ; Chronic Disease ; Cytokines/immunology/metabolism ; Dermatologic Agents/pharmacology/therapeutic use ; Dermatology/methods ; Humans ; Inflammation/drug therapy/immunology/microbiology ; Microbiota/drug effects/*immunology ; Skin/immunology/microbiology ; Skin Diseases/drug therapy/*immunology/microbiology ; }, abstract = {As humans age, our ability to manage certain types of inflammation is reduced. As a result, we experience chronic, low-grade inflammation, which has been termed &amp;ldquo;inflammaging&amp;rdquo;. This type of low-level inflammation is driven by a progressive increase in pro- inflammatory systemic cytokines over time. Inflammaging is thought to contribute to many age-related chronic diseases including cardiovascular disease, diabetes, Alzheimer’s disease, and even certain cancers. Recent studies suggest that the human microbiome may play a critical role in inflammaging. As the largest organ of the body and home to a significant portion of the human microbiome, the skin may play a unique role in inflammaging. In this review article, we present common dermatological diseases through the lens of inflammaging, look at how our skin may play a role in reducing inflammaging, and highlight the need for further focused research in this area. J Drugs Dermatol. 2021;20(2):144-149. doi:10.36849/JDD.5481.}, }
@article {pmid33535583, year = {2021}, author = {Oliva, M and Mulet-Margalef, N and Ochoa-De-Olza, M and Napoli, S and Mas, J and Laquente, B and Alemany, L and Duell, EJ and Nuciforo, P and Moreno, V}, title = {Tumor-Associated Microbiome: Where Do We Stand?.}, journal = {International journal of molecular sciences}, volume = {22}, number = {3}, pages = {}, pmid = {33535583}, issn = {1422-0067}, support = {27140/CRUK_/Cancer Research UK/United Kingdom ; }, mesh = {Animals ; Antineoplastic Agents/pharmacology ; Carcinogenesis ; Cell Transformation, Neoplastic ; Computational Biology ; Cytoplasm/metabolism ; Disease Progression ; Dysbiosis ; Gastrointestinal Microbiome/physiology ; *Gene Expression Regulation, Bacterial ; *Gene Expression Regulation, Neoplastic ; *Gene Expression Regulation, Viral ; Humans ; Immunity ; Metagenome ; Metagenomics ; Mice ; Microbiota/*physiology ; Neoplasms/*microbiology ; RNA, Ribosomal, 16S/metabolism ; *Tumor Microenvironment ; }, abstract = {The study of the human microbiome in oncology is a growing and rapidly evolving field. In the past few years, there has been an exponential increase in the number of studies investigating associations of microbiome and cancer, from oncogenesis and cancer progression to resistance or sensitivity to specific anticancer therapies. The gut microbiome is now known to play a significant role in antitumor immune responses and in predicting the efficacy of immune-checkpoint inhibitors in cancer patients. Beyond the gut, the tumor-associated microbiome-microbe communities located either in the tumor or within its body compartment-seems to interact with the local microenvironment and the tumor immune contexture, ultimately impacting cancer progression and treatment outcome. However, pre-clinical research focusing on causality and mechanistic pathways as well as proof-of-concept studies are still needed to fully understand the potential clinical utility of microbiome in cancer patients. Moreover, there is a need for the standardization of methodology and the implementation of quality control across microbiome studies to allow for a better interpretation and greater comparability of the results reported between them. This review summarizes the accumulating evidence in the field and discusses the current and upcoming challenges of microbiome studies.}, }
@article {pmid33529723, year = {2021}, author = {Palosuo, K and Karisola, P and Savinko, T and Fyhrquist, N and Alenius, H and Mäkelä, MJ}, title = {A Randomized, Open-Label Trial of Hen's Egg Oral Immunotherapy: Efficacy and Humoral Immune Responses in 50 Children.}, journal = {The journal of allergy and clinical immunology. In practice}, volume = {9}, number = {5}, pages = {1892-1901.e1}, doi = {10.1016/j.jaip.2021.01.020}, pmid = {33529723}, issn = {2213-2201}, mesh = {Administration, Oral ; Adolescent ; Allergens ; Animals ; Chickens ; Child ; *Desensitization, Immunologic ; *Egg Hypersensitivity/therapy ; Female ; Humans ; Immunity, Humoral ; Quality of Life ; }, abstract = {BACKGROUND: Egg allergy is the second most common food allergy in children. Persistent food allergy increases the risk of anaphylaxis and reduces the quality of life.<br><br>OBJECTIVE: To determine the efficacy of oral immunotherapy (OIT) with raw egg white powder and study its effects on humoral responses in children with persistent egg allergy.<br><br>METHODS: Fifty children aged 6 to 17 years with egg allergy, diagnosed by double-blind, placebo-controlled food challenge, were randomized 3:2 to 8 months of OIT with a maintenance dose of 1 g of egg white protein or 6 months of avoidance after which the avoidance group crossed over to OIT. We examined changes in IgE, IgG4, and IgA concentrations to Gal d 1-4 during OIT compared with avoidance and assessed clinical reactivity at 8 and 18 months.<br><br>RESULTS: After 8 months, 22 of 50 children (44%) on OIT and 1 of 21 (4.8%) on egg avoidance were desensitized to the target dose, 23 of 50 (46%) were partially desensitized (dose <1 g), and 5 of 50 (10%) discontinued. IgG4 concentrations to Gal d 1-4 and IgA to Gal d 1-2 increased significantly, whereas IgE to Gal d 2 decreased. A heatmap analysis of the IgE patterns revealed 3 distinct clusters linked with the clinical outcome. High baseline egg white-specific IgE and polysensitization to Gal d 1-4 related with failure to achieve the maintenance dose at 8 months. After 18 months of treatment, 36 of 50 patients (72%) were desensitized and 8 of 50 (16%) partially desensitized.<br><br>CONCLUSIONS: OIT with raw egg enables liberation of egg products into the daily diet in most patients. Subjects with high egg white-specific IgE concentrations and sensitization to multiple egg allergen components at baseline benefit from prolonged treatment.}, }
@article {pmid33519726, year = {2020}, author = {Fuller, KS and Torres Rivera, C}, title = {A Culturally Responsive Curricular Revision to Improve Engagement and Learning in an Undergraduate Microbiology Lab Course.}, journal = {Frontiers in microbiology}, volume = {11}, number = {}, pages = {577852}, pmid = {33519726}, issn = {1664-302X}, abstract = {We seek to increase student engagement and success to subsequently lead to increased retention and degree attainment for students at our Hispanic-serving institution. We hypothesized that using a culturally responsive approach in an undergraduate microbiology lab would increase engagement and learning gains. Using a culturally responsive approach allowed students to start their learning from their own place of understanding-centering students' lived experiences. Students interviewed family members to learn about "home remedies," and then devised experiments to test whether those home remedies affected growth of bacteria commonly implicated in gastrointestinal distress (Staphylococcus aureus, Bacillus cereus, and Escherichia coli) or sore throat (Neisseria gonorrhoeae, Streptococcus pyogenes, and Mycoplasma pneumoniae). As a final assessment, students generated project posters which they presented at a class symposium. Implementation of a culturally responsive research experience focused on the gut microbiome resulted in increased learning gains as evidenced by movement up Bloom's Revised Taxonomy Scale. Student feedback indicated increased engagement, increased confidence in communicating science and a deeper understanding and appreciation for microbiology. Taken together, the results indicate that students appreciate a more culturally responsive and student-centered approach to learning in microbiology and encourages expansion of this approach to other modules in the course. This paper includes responsive data to support this claim, as well as a sample course calendar and supplementary learning material to support the human microbiome approach to microbiology.}, }
@article {pmid33519207, year = {2021}, author = {Shah, V}, title = {Letter to the Editor: Microbiota in the Respiratory System-A Possible Explanation to Age and Sex Variability in Susceptibility to SARS-CoV-2.}, journal = {Microbiology insights}, volume = {14}, number = {}, pages = {1178636120988604}, pmid = {33519207}, issn = {1178-6361}, abstract = {The Human respiratory tract is colonized by a variety of microbes and the microbiota change as we age. In this perspective, literature support is presented for the hypothesis that the respiratory system microbiota could explain the differential age and sex breakdown amongst COVID-19 patients. The number of patients in the older and elderly adult group is higher than the other age groups. The perspective presents the possibility that certain genera of bacteria present in the respiratory system microbiota in children and young adults could be directly or through eliciting an immune response from the host, prevent full-fledged infection of SARS-CoV-2. The possibility also exists that the microbiota in older adults and the elderly population have bacteria that make it easier for the virus to cause infection. I call upon the scientific community to investigate the link between human microbiota and SARS-CoV-2 susceptibility to further understand the viral pathogenesis.}, }
@article {pmid33517907, year = {2021}, author = {Blaustein, RA and Michelitsch, LM and Glawe, AJ and Lee, H and Huttelmaier, S and Hellgeth, N and Ben Maamar, S and Hartmann, EM}, title = {Toothbrush microbiomes feature a meeting ground for human oral and environmental microbiota.}, journal = {Microbiome}, volume = {9}, number = {1}, pages = {32}, pmid = {33517907}, issn = {2049-2618}, support = {TL1 TR001423/TR/NCATS NIH HHS/United States ; }, mesh = {Adolescent ; Adult ; Aged ; *Built Environment ; Drug Resistance, Microbial/drug effects/genetics ; Humans ; Metagenome/drug effects/genetics ; *Microbiota/drug effects/genetics ; Middle Aged ; Mouth/drug effects/*microbiology ; *Toothbrushing ; Triclosan/pharmacology ; Young Adult ; }, abstract = {BACKGROUND: While indoor microbiomes impact our health and well-being, much remains unknown about taxonomic and functional transitions that occur in human-derived microbial communities once they are transferred away from human hosts. Toothbrushes are a model to investigate the potential response of oral-derived microbiota to conditions of the built environment. Here, we characterize metagenomes of toothbrushes from 34 subjects to define the toothbrush microbiome and resistome and possible influential factors.<br><br>RESULTS: Toothbrush microbiomes often comprised a dominant subset of human oral taxa and less&#xa0;abundant or&#xa0;site-specific environmental strains. Although toothbrushes contained lower taxonomic diversity than oral-associated counterparts (determined by comparison with the Human Microbiome Project), they had relatively broader antimicrobial resistance gene (ARG) profiles. Toothbrush resistomes were enriched with a variety of ARGs, notably those conferring multidrug efflux and putative resistance to triclosan, which were primarily attributable to versatile environmental taxa. Toothbrush microbial communities and resistomes correlated with a variety of factors linked to personal health, dental hygiene, and bathroom features.<br><br>CONCLUSIONS: Selective pressures in the built environment may shape the dynamic mixture of human (primarily oral-associated) and environmental microbiota that encounter each other on toothbrushes. Harboring a microbial diversity and resistome distinct from human-associated counterparts suggests toothbrushes could potentially serve as a reservoir that may enable the transfer of ARGs. Video abstract.}, }
@article {pmid33515779, year = {2021}, author = {Cohen, I and Ruff, WE and Longbrake, EE}, title = {Influence of immunomodulatory drugs on the gut microbiota.}, journal = {Translational research : the journal of laboratory and clinical medicine}, volume = {233}, number = {}, pages = {144-161}, pmid = {33515779}, issn = {1878-1810}, support = {K23 NS107624/NS/NINDS NIH HHS/United States ; }, mesh = {Adaptive Immunity/drug effects ; Cell Proliferation/drug effects ; Cytokines/antagonists &amp; inhibitors ; Female ; Gastrointestinal Microbiome/*drug effects/*immunology ; Host Microbial Interactions/drug effects/immunology ; Humans ; Immune Checkpoint Inhibitors/pharmacology ; Immunity, Innate/drug effects ; Immunity, Mucosal/drug effects ; Immunologic Factors/*pharmacology ; Immunomodulation ; Lymphocytes/drug effects ; Male ; Models, Immunological ; Sex Factors ; Translational Research, Biomedical ; }, abstract = {Immunomodulatory medications are a mainstay of treatment for autoimmune diseases and malignancies. In addition to their direct effects on immune cells, these medications also impact the gut microbiota. Drug-induced shifts in commensal microbes can lead to indirect but important changes in the immune response. We performed a comprehensive literature search focusing on immunotherapy/microbe interactions. Immunotherapies were categorized into 5 subtypes based on their mechanisms of action: cell trafficking inhibitors, immune checkpoint inhibitors, immunomodulators, antiproliferative drugs, and inflammatory cytokine inhibitors. Although no consistent relationships were observed between types of immunotherapy and microbiota, most immunotherapies were associated with shifts in specific colonizing bacterial taxa. The relationships between colonizing microbes and drug efficacy were not well-studied for autoimmune diseases. In contrast, the efficacy of immune checkpoint inhibitors for cancer was tied to the baseline composition of the gut microbiota. There was a paucity of high-quality data; existing data were generated using heterogeneous sampling and analytic techniques, and most studies involved small numbers of participants. Further work is needed to elucidate the extent and clinical significance of immunotherapy effects on the human microbiome.}, }
@article {pmid33511356, year = {2021}, author = {Helve, O and Dikareva, E and Stefanovic, V and Kolho, KL and Salonen, A and de Vos, WM and Andersson, S}, title = {Protocol for oral transplantation of maternal fecal microbiota to newborn infants born by cesarean section.}, journal = {STAR protocols}, volume = {2}, number = {1}, pages = {100271}, pmid = {33511356}, issn = {2666-1667}, mesh = {Cesarean Section ; *Fecal Microbiota Transplantation ; Female ; Humans ; Infant, Newborn ; Pregnancy ; }, abstract = {Infants born by cesarean section have an intestinal microbiota that differs from that of infants delivered vaginally. Here, we report a protocol for performing oral transplantation of maternal fecal microbiota to newborn infants born by elective cesarean section. The crucial step of this protocol is the health screening process. This protocol can only be applied to healthy mothers and infants. For complete details on the use and execution of this protocol, please refer to Korpela et al. (2020).}, }
@article {pmid33505891, year = {2021}, author = {Arbizu, RA and Collins, D and Wilson, RC and Alekseyenko, AV}, title = {Evidence for Differentiation of Colon Tissue Microbiota in Patients with and without Postoperative Hirschsprung's Associated Enterocolitis: A Pilot Study.}, journal = {Pediatric gastroenterology, hepatology &amp; nutrition}, volume = {24}, number = {1}, pages = {30-37}, pmid = {33505891}, issn = {2234-8646}, support = {R01 LM012517/LM/NLM NIH HHS/United States ; U54 CA210963/CA/NCI NIH HHS/United States ; UL1 TR001450/TR/NCATS NIH HHS/United States ; }, abstract = {PURPOSE: To investigate the differences in the colon microbiota composition of Hirschsprung's disease (HSCR) patients with and without a history of postoperative Hirschsprung's associated enterocolitis (HAEC).<br><br>METHODS: Colon tissue microbiota was characterized by bacterial deoxyribonucleic acid (DNA) extraction and 16S rDNA sequencing for taxonomic classification and comparison.<br><br>RESULTS: The sequence diversity richness within samples was significantly higher in samples from patients with a history of postoperative HAEC. We observed an increased relative abundance of the phyla Bacteroidetes, Firmicutes and Cyanobacteria in HAEC patients and Fusobacteria, Actinobacteria and Proteobacteria in HSCR patients and, an increased relative abundance of the genera Dolosigranulum, Roseouria and Streptococcus in HAEC patients and Propionibacterium and Delftia in HSCR patients.<br><br>CONCLUSION: Our findings provide evidence that the colon tissue microbiota composition is different in HSCR patients with and without postoperative HAEC.}, }
@article {pmid33505390, year = {2020}, author = {Livson, S and Jarva, H and Kalliala, I and Lokki, AI and Heikkinen-Eloranta, J and Nieminen, P and Meri, S}, title = {Activation of the Complement System in the Lower Genital Tract During Pregnancy and Delivery.}, journal = {Frontiers in immunology}, volume = {11}, number = {}, pages = {563073}, pmid = {33505390}, issn = {1664-3224}, mesh = {Adolescent ; Adult ; Cervix Mucus/immunology ; Cervix Uteri/*immunology ; *Complement Activation ; Complement C3/*immunology ; Enzyme-Linked Immunosorbent Assay ; Female ; Humans ; *Immunity, Humoral ; Immunoglobulin A/immunology ; Immunoglobulin G/immunology ; Parturition/*immunology ; Pregnancy ; Vagina/*immunology ; Young Adult ; }, abstract = {BACKGROUND: Human pregnancy alters profoundly the immune system. The local involvement and mechanisms of activation of the complement system in the cervicovaginal milieu during pregnancy and delivery remain unexplored.<br><br>OBJECTIVES: To determine whether normal pregnancy and delivery are associated with local activation of complement or changes in the immunoglobulin profile in the cervix.<br><br>STUDY DESIGN: This study was designed to assess IgA, IgG, and complement activation in the cervicovaginal area in three groups of patients: i) 49 pregnant women (week 41+3-42+0) not in active labor, ii) 24 women in active labor (38+4-42+2), and iii) a control group of nonpregnant women (n=23) at child-bearing age. We collected mucosal samples from the lateral fornix of the vagina and external cervix during routine visits and delivery. The Western blot technique was used to detect complement C3 and its activation products. For semiquantitative analysis, the bands of the electrophoresed proteins in gels were digitized on a flatbed photo scanner and analyzed. IgA and IgG were analyzed by Western blotting and quantified by ELISA. One-way ANOVA and Tukey's Multiple Comparison tests were used for statistical comparisons.<br><br>RESULTS: A higher abundance but lower activation level of C3 in both the external cervix (P<0.001) and lateral fornix of the vagina (P<0.001) was observed during delivery (58 &#xb1; 22, n= 24) in comparison to the groups of nonpregnant (72 &#xb1; 13%; mean &#xb1; SD, n=23) and pregnant women (78 &#xb1; 22%, n=49). Complement activating IgG was detected in higher abundance than IgA in the cervicovaginal secretions of pregnant women. In a small proportion samples also C3-IgG complexes were detected.<br><br>CONCLUSIONS: Our results reveal an unexpectedly strong activation of the complement system and the presence IgG immunoglobulins in the cervicovaginal area during pregnancy, active labor, and among nonpregnant women. In contrast to the higher amounts of C3 in the cervicovaginal secretions during labor, its activation level was lower. Complement activating IgG was detected in higher concentrations than IgA in the mucosal secretions during pregnancy and labor. Taken together our results imply the presence a locally operating humoral immune system in the cervicovaginal mucosa.}, }
@article {pmid33501942, year = {2021}, author = {Karjalainen, EK and Renkonen-Sinisalo, L and Satokari, R and Mustonen, H and Ristimäki, A and Arkkila, P and Lepistö, AH}, title = {Fecal Microbiota Transplantation in Chronic Pouchitis: A Randomized, Parallel, Double-Blinded Clinical Trial.}, journal = {Inflammatory bowel diseases}, volume = {27}, number = {11}, pages = {1766-1772}, pmid = {33501942}, issn = {1536-4844}, mesh = {Anti-Bacterial Agents/therapeutic use ; Chronic Disease ; *Colitis, Ulcerative/complications/drug therapy ; *Fecal Microbiota Transplantation ; Humans ; *Pouchitis/etiology/therapy ; }, abstract = {BACKGROUND: In ulcerative colitis, a pouchitis is the most common long-term adverse effect after proctocolectomy and ileal pouch-anal anastomosis. Approximately 5% of patients develop chronic antibiotic-dependent or antibiotic-refractory pouchitis without any effective treatment. The aim of this trial was to investigate the efficacy and safety of fecal microbiota transplantation in the treatment of chronic pouchitis.<br><br>METHODS: This was a single-center, double-blinded, parallel group trial comparing donor fecal microbiota transplantation with placebo (autologous transplant) in chronic pouchitis. Twenty-six patients were recruited at the Helsinki University Hospital between December 2017 and August 2018 and were randomly allocated a 1:1 ratio to either donor fecal microbiota transplantation or placebo. The protocol included 2 transplantations into the pouch on weeks 0 and 4, and patients were followed up for 52 weeks.<br><br>RESULTS: Nine patients in the intervention group and 8 patients in the placebo group relapsed during the 52-week follow-up, and the relapse-free survival did not differ between the groups (P = 0.183, log-rank; hazard ratio, 1.90 [95% confidence interval, 0.73-4.98; P = 0.190]). In the subgroup analysis of patients using continuous antibiotics before the study, the relapse-free survival was shorter in the intervention group (P = 0.004, log-rank; hazard ratio, 13.08 [95% confidence interval, 1.47-116.60; P = 0.021]). No major adverse effects were reported.<br><br>CONCLUSIONS: The fecal microbiota transplantation treatment regime used in our study was not effective in the treatment of chronic pouchitis. The safety profile of fecal microbiota transplantation was good.<br><br>CLINICALTRIALS.GOV IDENTIFIER: NCT03378921.}, }
@article {pmid33501940, year = {2021}, author = {Karjalainen, EK and Renkonen-Sinisalo, L and Satokari, R and Mustonen, H and Ristimäki, A and Arkkila, P and Lepistö, AH}, title = {Author's Reply: Fecal Microbiota Transplantation for Chronic Pouchitis: Promising Novel Therapeutic or Lost Cause?.}, journal = {Inflammatory bowel diseases}, volume = {27}, number = {7}, pages = {e79-e80}, doi = {10.1093/ibd/izab003}, pmid = {33501940}, issn = {1536-4844}, mesh = {*Colitis, Ulcerative ; Fecal Microbiota Transplantation ; Humans ; *Pouchitis/therapy ; }, }
@article {pmid33499948, year = {2020}, author = {Li, X and Trivedi, U and Brejnrod, AD and Vestergaard, G and Mortensen, MS and Bertelsen, MF and Sørensen, SJ}, title = {The microbiome of captive hamadryas baboons.}, journal = {Animal microbiome}, volume = {2}, number = {1}, pages = {25}, pmid = {33499948}, issn = {2524-4671}, support = {11106571//Danmarks Frie Forskningsfond (DK)/ ; }, abstract = {BACKGROUND: The hamadryas baboon (Papio hamadryas) is a highly social primate that lives in complex multilevel societies exhibiting a wide range of group behaviors akin to humans. In contrast to the widely studied human microbiome, there is a paucity of information on the host-associated microbiomes of nonhuman primates (NHPs). Here, our goal was to understand the microbial composition throughout different body sites of cohabiting baboons.<br><br>RESULTS: We analyzed 170 oral, oropharyngeal, cervical, uterine, vaginal, nasal and rectal samples from 16 hamadryas baboons via 16S rRNA gene sequencing. Additionally, raw Miseq sequencing data from 1041 comparable publicly available samples from the human oral cavity, gut and vagina were reanalyzed using the same pipeline. We compared the baboon and human microbiome of the oral cavity, gut and vagina, showing that the baboon microbiome is distinct from the human. Baboon cohabitants share similar microbial profiles in their cervix, uterus, vagina, and gut. The oral cavity, gut and vagina shared more bacterial amplicon sequence variants (ASVs) in group living baboons than in humans. The shared ASVs had significantly positive correlations between most body sites, suggesting a potential bacterial exchange throughout the body. No significant differences in gut microbiome composition were detected within the maternity line and between maternity lines, suggesting that the offspring gut microbiota is shaped primarily through bacterial exchange among cohabitants. Finally, Lactobacillus was not so predominant in baboon vagina as in the human vagina but was the most abundant genus in the baboon gut.<br><br>CONCLUSIONS: This study is the first to provide comprehensive analyses of the baboon microbiota across different body sites. We contrast this to human body sites and find substantially different microbiomes. This group of cohabitating baboons generally showed higher microbial diversity and remarkable similarities between body sites than were observed in humans. These data and findings from one group of baboons can form the basis of future microbiome studies in baboons and be used as a reference in research where the microbiome is expected to impact human modeling with baboons.}, }
@article {pmid33498226, year = {2021}, author = {Garcia, EM and Serrano, MG and Edupuganti, L and Edwards, DJ and Buck, GA and Jefferson, KK}, title = {Sequence Comparison of Vaginolysin from Different Gardnerella Species.}, journal = {Pathogens (Basel, Switzerland)}, volume = {10}, number = {2}, pages = {}, pmid = {33498226}, issn = {2076-0817}, support = {UH2 AI083263/AI/NIAID NIH HHS/United States ; U54 DE023786/NH/NIH HHS/United States ; U54 HD080784/HD/NICHD NIH HHS/United States ; R01 HD092415/HD/NICHD NIH HHS/United States ; UH3 AI083263/AI/NIAID NIH HHS/United States ; U54 DE023786/DE/NIDCR NIH HHS/United States ; }, abstract = {Gardnerella vaginalis has recently been split into 13 distinct species. In this study, we tested the hypotheses that species-specific variations in the vaginolysin (VLY) amino acid sequence could influence the interaction between the toxin and vaginal epithelial cells and that VLY variation may be one factor that distinguishes less virulent or commensal strains from more virulent strains. This was assessed by bioinformatic analyses of publicly available Gardnerella spp. sequences and quantification of cytotoxicity and cytokine production from purified, recombinantly produced versions of VLY. After identifying conserved differences that could distinguish distinct VLY types, we analyzed metagenomic data from a cohort of female subjects from the Vaginal Human Microbiome Project to investigate whether these different VLY types exhibited any significant associations with symptoms or Gardnerella spp.-relative abundance in vaginal swab samples. While Type 1 VLY was most prevalent among the subjects and may be associated with increased reports of symptoms, subjects with Type 2 VLY dominant profiles exhibited increased relative Gardnerella spp. abundance. Our findings suggest that amino acid differences alter the interaction of VLY with vaginal keratinocytes, which may potentiate differences in bacterial vaginosis (BV) immunopathology in vivo.}, }
@article {pmid33498157, year = {2021}, author = {Rusanen, J and Kareinen, L and Levanov, L and Mero, S and Pakkanen, SH and Kantele, A and Amanat, F and Krammer, F and Hedman, K and Vapalahti, O and Hepojoki, J}, title = {A 10-Minute "Mix and Read" Antibody Assay for SARS-CoV-2.}, journal = {Viruses}, volume = {13}, number = {2}, pages = {}, pmid = {33498157}, issn = {1999-4915}, support = {-//Sigrid Jus&#xe9;liuksen S&#xe4;&#xe4;ti&#xf6;/International ; Programme VEO (Versatile emerging infectious disease observatory), grant No. 874735//H2020 Health/International ; -//Jane ja Aatos Erkon S&#xe4;&#xe4;ti&#xf6;/International ; -//Magnus Ehrnroothin S&#xe4;&#xe4;ti&#xf6;/International ; -//Juho Vainion S&#xe4;&#xe4;ti&#xf6;/International ; -//Suomen Tiedeseura/International ; -//Helsingin Yliopisto/International ; #1308613, #1336490, #336439 and #335527//Academy of Finland/International ; HHSN272201400008C/AI/NIAID NIH HHS/United States ; -//Finska L&#xe4;kares&#xe4;llskapet/International ; TYH 2018322//Helsingin ja Uudenmaan Sairaanhoitopiiri/International ; 4147//Suomen L&#xe4;&#xe4;ketieteen S&#xe4;&#xe4;ti&#xf6;/International ; 75N93019C00051/AI/NIAID NIH HHS/United States ; }, mesh = {Antibodies, Neutralizing/blood ; Antibodies, Viral/blood ; COVID-19/blood/*diagnosis ; COVID-19 Serological Testing/*methods ; Coronavirus Nucleocapsid Proteins/immunology ; Humans ; Immunoassay/*methods ; Phosphoproteins/immunology ; SARS-CoV-2/immunology/*isolation &amp; purification ; Sensitivity and Specificity ; Spike Glycoprotein, Coronavirus/immunology ; }, abstract = {Accurate and rapid diagnostic tools are needed for management of the ongoing coronavirus disease 2019 (COVID-19) pandemic. Antibody tests enable detection of individuals past the initial phase of infection and help examine vaccine responses. The major targets of human antibody response in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are the spike glycoprotein (SP) and nucleocapsid protein (NP). We have developed a rapid homogenous approach for antibody detection termed LFRET (protein L-based time-resolved Förster resonance energy transfer immunoassay). In LFRET, fluorophore-labeled protein L and antigen are brought to close proximity by antigen-specific patient immunoglobulins of any isotype, resulting in TR-FRET signal. We set up LFRET assays for antibodies against SP and NP and evaluated their diagnostic performance using a panel of 77 serum/plasma samples from 44 individuals with COVID-19 and 52 negative controls. Moreover, using a previously described SP and a novel NP construct, we set up enzyme linked immunosorbent assays (ELISAs) for antibodies against SARS-CoV-2 SP and NP. We then compared the LFRET assays with these ELISAs and with a SARS-CoV-2 microneutralization test (MNT). We found the LFRET assays to parallel ELISAs in sensitivity (90-95% vs. 90-100%) and specificity (100% vs. 94-100%). In identifying individuals with or without a detectable neutralizing antibody response, LFRET outperformed ELISA in specificity (91-96% vs. 82-87%), while demonstrating an equal sensitivity (98%). In conclusion, this study demonstrates the applicability of LFRET, a 10-min "mix and read" assay, to detection of SARS-CoV-2 antibodies.}, }
@article {pmid33492450, year = {2021}, author = {Grenda, A and Krawczyk, P}, title = {Cancer trigger or remedy: two faces of the human microbiome.}, journal = {Applied microbiology and biotechnology}, volume = {105}, number = {4}, pages = {1395-1405}, pmid = {33492450}, issn = {1432-0614}, mesh = {Dysbiosis ; Faecalibacterium prausnitzii ; *Gastrointestinal Microbiome ; Humans ; *Microbiota ; *Neoplasms/drug therapy ; }, abstract = {Currently, increasing attention cancer treatment has focused on molecularly targeted therapies and more recently on immunotherapies targeting immune checkpoints. However, even such advanced treatment may be ineffective. The reasons for this are sought, inter alia, in the human microbiome. In our intestines, there are bacteria that are beneficial to us, but pathogenic microorganisms may also be present. Microbial imbalance (dysbiosis) is now perceived as one of the gateways to cancer. However, it is feasible to use bacteria and their metabolites to restore the natural, beneficial microbiome during oncological treatment. Akkermansia mucinifila, Enterococcus hirae, or Faecalibacterium prausnitzii are bacteria that exhibit this beneficial potential. Greater benefits of therapy can be observed in cancer patients enriched in these bacterial species and treated with anti-PD-1, anti-PD-L1, or anti-CTLA-4 monoclonal antibodies. In this review, we present issues related to the role of bacteria in carcinogenesis and their therapeutic potential "supporting" modern anti-cancer therapies.Key Points• Bacteria can be directly or indirectly a cancer trigger.• Bacterial metabolites regulate the pathways associated with carcinogenesis.• Intestinal bacteria activate the immune system to fight cancer.}, }
@article {pmid33488555, year = {2020}, author = {Luo, Z and Alekseyenko, AV and Ogunrinde, E and Li, M and Li, QZ and Huang, L and Tsao, BP and Kamen, DL and Oates, JC and Li, Z and Gilkeson, GS and Jiang, W}, title = {Rigorous Plasma Microbiome Analysis Method Enables Disease Association Discovery in Clinic.}, journal = {Frontiers in microbiology}, volume = {11}, number = {}, pages = {613268}, pmid = {33488555}, issn = {1664-302X}, support = {U54 CA210962/CA/NCI NIH HHS/United States ; R01 AR071410/AR/NIAMS NIH HHS/United States ; R01 AI128864/AI/NIAID NIH HHS/United States ; P30 CA138313/CA/NCI NIH HHS/United States ; P30 AR072582/AR/NIAMS NIH HHS/United States ; R01 LM012517/LM/NLM NIH HHS/United States ; I01 CX001211/CX/CSRD VA/United States ; UL1 RR029882/RR/NCRR NIH HHS/United States ; T32 AR050958/AR/NIAMS NIH HHS/United States ; M01 RR001070/RR/NCRR NIH HHS/United States ; P50 AR070591/AR/NIAMS NIH HHS/United States ; UL1 TR001450/TR/NCATS NIH HHS/United States ; R21 AR067459/AR/NIAMS NIH HHS/United States ; P30 DK123704/DK/NIDDK NIH HHS/United States ; K24 AR068406/AR/NIAMS NIH HHS/United States ; R01 CA213290/CA/NCI NIH HHS/United States ; R21 TR002513/TR/NCATS NIH HHS/United States ; R01 AR071947/AR/NIAMS NIH HHS/United States ; R01 CA164964/CA/NCI NIH HHS/United States ; P60 AR062755/AR/NIAMS NIH HHS/United States ; }, abstract = {Blood microbiome is important to investigate microbial-host interactions and the effects on systemic immune perturbations. However, this effort has met with major challenges due to low microbial biomass and background artifacts. In the current study, microbial 16S DNA sequencing was applied to analyze plasma microbiome. We have developed a quality-filtering strategy to evaluate and exclude low levels of microbial sequences, potential contaminations, and artifacts from plasma microbial 16S DNA sequencing analyses. Furthermore, we have applied our technique in three cohorts, including tobacco-smokers, HIV-infected individuals, and individuals with systemic lupus erythematosus (SLE), as well as corresponding controls. More than 97% of total sequence data was removed using stringent quality-filtering strategy analyses; those removed amplicon sequence variants (ASVs) were low levels of microbial sequences, contaminations, and artifacts. The specifically enriched pathobiont bacterial ASVs have been identified in plasmas from tobacco-smokers, HIV-infected individuals, and individuals with SLE but not from control subjects. The associations between these ASVs and disease pathogenesis were demonstrated. The pathologic activities of some identified bacteria were further verified in vitro. We present a quality-filtering strategy to identify pathogenesis-associated plasma microbiome. Our approach provides a method for studying the diagnosis of subclinical microbial infection as well as for understanding the roles of microbiome-host interaction in disease pathogenesis.}, }
@article {pmid33483519, year = {2021}, author = {Simon-Soro, A and Kim, D and Li, Y and Liu, Y and Ito, T and Sims, KR and Benoit, DSW and Bittinger, K and Koo, H}, title = {Impact of the repurposed drug thonzonium bromide on host oral-gut microbiomes.}, journal = {NPJ biofilms and microbiomes}, volume = {7}, number = {1}, pages = {7}, pmid = {33483519}, issn = {2055-5008}, support = {R01 DE018023/DE/NIDCR NIH HHS/United States ; R01 DE025220/DE/NIDCR NIH HHS/United States ; F31 DE026944/DE/NIDCR NIH HHS/United States ; }, mesh = {Animals ; Bacteria/classification/drug effects/isolation &amp; purification ; Dental Caries/drug therapy/microbiology ; Disease Models, Animal ; *Drug Repositioning ; Feces/microbiology ; Gastrointestinal Microbiome/drug effects ; Humans ; Microbiota/*drug effects ; Mouth/*microbiology ; Pyrimidines/*pharmacology/therapeutic use ; Quaternary Ammonium Compounds/*pharmacology/therapeutic use ; Rats ; }, abstract = {Drug repurposing is a feasible strategy for the development of novel therapeutic applications. However, its potential use for oral treatments and impact on host microbiota remain underexplored. Here, we assessed the influences of topical oral applications of a repurposed FDA-approved drug, thonzonium bromide, on gastrointestinal microbiomes and host tissues in a rat model of dental caries designed to reduce cross-contamination associated with coprophagy. Using this model, we recapitulated the body site microbiota that mirrored the human microbiome profile. Oral microbiota was perturbed by the treatments with specific disruption of Rothia and Veillonella without affecting the global composition of the fecal microbiome. However, disturbances in the oral-gut microbial interactions were identified using nestedness and machine learning, showing increased sharing of oral taxon Sutterella in the gut microbiota. Host-tissue analyses revealed caries reduction on teeth by thonzonium bromide without cytotoxic effects, indicating bioactivity and biocompatibility when used orally. Altogether, we demonstrate how an oral treatment using a repurposed drug causes localized microbial disturbances and therapeutic effects while promoting turnover of specific oral species in the lower gut in vivo.}, }
@article {pmid33482907, year = {2021}, author = {Loomis, KH and Wu, SK and Ernlund, A and Zudock, K and Reno, A and Blount, K and Karig, DK}, title = {A mixed community of skin microbiome representatives influences cutaneous processes more than individual members.}, journal = {Microbiome}, volume = {9}, number = {1}, pages = {22}, pmid = {33482907}, issn = {2049-2618}, mesh = {Filaggrin Proteins ; Gene Expression Profiling ; Healthy Volunteers ; *Host Microbial Interactions/genetics ; Humans ; *Microbiota/genetics ; Skin/*metabolism/*microbiology ; *Skin Physiological Phenomena/genetics ; }, abstract = {BACKGROUND: Skin, the largest organ of the human body by weight, hosts a diversity of microorganisms that can influence health. The microbial residents of the skin are now appreciated for their roles in host immune interactions, wound healing, colonization resistance, and various skin disorders. Still, much remains to be discovered in terms of the host pathways influenced by skin microorganisms, as well as the higher-level skin properties impacted through these microbe-host interactions. Towards this direction, recent efforts using mouse models point to pronounced changes in the transcriptional profiles of the skin in response to the presence of a microbial community. However, there is a need to quantify the roles of microorganisms at both the individual and community-level in healthy human skin. In this study, we utilize human skin equivalents to study the effects of individual taxa and a microbial community in a precisely controlled context. Through transcriptomics analysis, we identify key genes and pathways influenced by skin microbes, and we also characterize higher-level impacts on skin processes and properties through histological analyses.<br><br>RESULTS: The presence of a microbiome on a 3D skin tissue model led to significantly altered patterns of gene expression, influencing genes involved in the regulation of apoptosis, proliferation, and the extracellular matrix (among others). Moreover, microbiome treatment influenced the thickness of the epidermal layer, reduced the number of actively proliferating cells, and increased filaggrin expression. Many of these findings were evident upon treatment with the mixed community, but either not detected or less pronounced in treatments by single microorganisms, underscoring the impact that a diverse skin microbiome has on the host.<br><br>CONCLUSIONS: This work contributes to the understanding of how microbiome constituents individually and collectively influence human skin processes and properties. The results show that, while it is important to understand the effect of individual microbes on the host, a full community of microbes has unique and pronounced effects on the skin. Thus, in its impacts on the host, the skin microbiome is more than the sum of its parts. Video abstract.}, }
@article {pmid33477821, year = {2021}, author = {Depommier, C and Vitale, RM and Iannotti, FA and Silvestri, C and Flamand, N and Druart, C and Everard, A and Pelicaen, R and Maiter, D and Thissen, JP and Loumaye, A and Hermans, MP and Delzenne, NM and de Vos, WM and Di Marzo, V and Cani, PD}, title = {Beneficial Effects of Akkermansia muciniphila Are Not Associated with Major Changes in the Circulating Endocannabinoidome but Linked to Higher Mono-Palmitoyl-Glycerol Levels as New PPARα Agonists.}, journal = {Cells}, volume = {10}, number = {1}, pages = {}, pmid = {33477821}, issn = {2073-4409}, support = {//CIHR/Canada ; }, mesh = {Adult ; Akkermansia ; Animals ; COS Cells ; Chlorocebus aethiops ; Endocannabinoids/*blood ; Female ; Humans ; Male ; *Metabolic Syndrome/blood/therapy ; Monoglycerides/*blood ; *Obesity/blood/therapy ; *PPAR alpha/agonists/metabolism ; }, abstract = {Akkermansia muciniphila is considered as one of the next-generation beneficial bacteria in the context of obesity and associated metabolic disorders. Although a first proof-of-concept of its beneficial effects has been established in the context of metabolic syndrome in humans, mechanisms are not yet fully understood. This study aimed at deciphering whether the bacterium exerts its beneficial properties through the modulation of the endocannabinoidome (eCBome). Circulating levels of 25 endogenous endocannabinoid-related lipids were quantified by liquid chromatography with tandem mass spectrometry (LC-MS/MS) in the plasma of overweight or obese individuals before and after a 3 months intervention consisting of the daily ingestion of either alive or pasteurized A. muciniphila. Results from multivariate analyses suggested that the beneficial effects of A. muciniphila were not linked to an overall modification of the eCBome. However, subsequent univariate analysis showed that the decrease in 1-Palmitoyl-glycerol (1-PG) and 2-Palmitoyl-glycerol (2-PG), two eCBome lipids, observed in the placebo group was significantly counteracted by the alive bacterium, and to a lower extent by the pasteurized form. We also discovered that 1- and 2-PG are endogenous activators of peroxisome proliferator-activated receptor alpha (PPARα). We hypothesize that PPARα activation by mono-palmitoyl-glycerols may underlie part of the beneficial metabolic effects induced by A. muciniphila in human metabolic syndrome.}, }
@article {pmid33472859, year = {2021}, author = {Finlay, BB and Amato, KR and Azad, M and Blaser, MJ and Bosch, TCG and Chu, H and Dominguez-Bello, MG and Ehrlich, SD and Elinav, E and Geva-Zatorsky, N and Gros, P and Guillemin, K and Keck, F and Korem, T and McFall-Ngai, MJ and Melby, MK and Nichter, M and Pettersson, S and Poinar, H and Rees, T and Tropini, C and Zhao, L and Giles-Vernick, T}, title = {The hygiene hypothesis, the COVID pandemic, and consequences for the human microbiome.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {118}, number = {6}, pages = {}, pmid = {33472859}, issn = {1091-6490}, support = {P01 GM125576/GM/NIGMS NIH HHS/United States ; }, mesh = {Aged ; Anti-Infective Agents/therapeutic use ; COVID-19/*microbiology/mortality ; Eating ; Female ; Humans ; *Hygiene Hypothesis ; Infant ; Infection Control/methods ; Male ; *Microbiota/drug effects ; Physical Distancing ; Pregnancy ; }, abstract = {The COVID-19 pandemic has the potential to affect the human microbiome in infected and uninfected individuals, having a substantial impact on human health over the long term. This pandemic intersects with a decades-long decline in microbial diversity and ancestral microbes due to hygiene, antibiotics, and urban living (the hygiene hypothesis). High-risk groups succumbing to COVID-19 include those with preexisting conditions, such as diabetes and obesity, which are also associated with microbiome abnormalities. Current pandemic control measures and practices will have broad, uneven, and potentially long-term effects for the human microbiome across the planet, given the implementation of physical separation, extensive hygiene, travel barriers, and other measures that influence overall microbial loss and inability for reinoculation. Although much remains uncertain or unknown about the virus and its consequences, implementing pandemic control practices could significantly affect the microbiome. In this Perspective, we explore many facets of COVID-19-induced societal changes and their possible effects on the microbiome, and discuss current and future challenges regarding the interplay between this pandemic and the microbiome. Recent recognition of the microbiome's influence on human health makes it critical to consider both how the microbiome, shaped by biosocial processes, affects susceptibility to the coronavirus and, conversely, how COVID-19 disease and prevention measures may affect the microbiome. This knowledge may prove key in prevention and treatment, and long-term biological and social outcomes of this pandemic.}, }
@article {pmid33459632, year = {2021}, author = {Cuñé Castellana, J}, title = {[Microbioma and lithiasis.].}, journal = {Archivos espanoles de urologia}, volume = {74}, number = {1}, pages = {157-170}, pmid = {33459632}, issn = {0004-0614}, mesh = {*Gastrointestinal Microbiome ; Humans ; *Lithiasis ; Prebiotics ; *Probiotics ; *Urinary Tract ; }, abstract = {Human microbiome understanding and its relationship with health has represented a revolution in biomedicine, facilitated by the emergence of new molecular microbiology techniques. Lithiasic pathology has not been alien to this new approach to etiological knowledge. As a result of this research activity, it has been possible to elucidate the importance of the intestine-kidney axis, understood as the impact of the intestinal microbiota on nephrourinary health. In this regard the ability to use oxalate as an energy source by certain intestinal microorganisms has been used as a target form odulators of the intestinal microbiota in order to correcthyperoxaluria, both primary and secondary. However,the importance of the microbiome configuration, and its role in oxalocalcic lithiasis, transcends the existence of certain trophic networks. In particular, intestinal microbiome has the ability to promote tubular lesions resulting from oxidative stress caused by chronic low-grade inflammation, closely linked to the composition of the microbiota and the dialogue established with the immune system at the intestinal level. The importance of the urobiome, a stable microbia lstructure residing in the urinary tract, allowed to calibrate the importance of urinary microorganisms in lithiasic pathology, breaking with the paradigm of urine sterility in healthy conditions. Thus, recent studies suggest that the composition and structure of the urobiome have a crucial impact on infectious but also non-infectious lithiasis, since certain microorganisms can act as nucleants and promoters of the lithogenic process. Associated with the advances in the study of binomial microbiota and lithiasic pathology, new ways are opened for patient management, in terms of prevention and treatment, based on intervention on the microbiome. Future therapeutic arsenal, in addition to probiotics and prebiotics, will integrate consortia of different microbial groups and microbiota transplantation, both urinary and intestinal.}, }
@article {pmid33449153, year = {2021}, author = {Strickland, AB and Shi, M}, title = {Mechanisms of fungal dissemination.}, journal = {Cellular and molecular life sciences : CMLS}, volume = {78}, number = {7}, pages = {3219-3238}, pmid = {33449153}, issn = {1420-9071}, support = {R01 AI131905/AI/NIAID NIH HHS/United States ; R21 AI131219/AI/NIAID NIH HHS/United States ; AI131905/NH/NIH HHS/United States ; AI131219/NH/NIH HHS/United States ; AI131219/NH/NIH HHS/United States ; AI131905/NH/NIH HHS/United States ; }, mesh = {Animals ; Antifungal Agents/*therapeutic use ; Fungi/classification/isolation &amp; purification/*pathogenicity ; Host-Pathogen Interactions/drug effects/*immunology ; Humans ; Mycoses/*drug therapy/microbiology ; Virulence ; }, abstract = {Fungal infections are an increasing threat to global public health. There are more than six million fungal species worldwide, but less than 1% are known to infect humans. Most of these fungal infections are superficial, affecting the hair, skin and nails, but some species are capable of causing life-threatening diseases. The most common of these include Cryptococcus neoformans, Aspergillus fumigatus and Candida albicans. These fungi are typically innocuous and even constitute a part of the human microbiome, but if these pathogens disseminate throughout the body, they can cause fatal infections which account for more than one million deaths worldwide each year. Thus, systemic dissemination of fungi is a critical step in the development of these deadly infections. In this review, we discuss our current understanding of how fungi disseminate from the initial infection sites to the bloodstream, how immune cells eliminate fungi from circulation and how fungi leave the blood and enter distant organs, highlighting some recent advances and offering some perspectives on future directions.}, }
@article {pmid33440171, year = {2021}, author = {Tanes, C and Bittinger, K and Gao, Y and Friedman, ES and Nessel, L and Paladhi, UR and Chau, L and Panfen, E and Fischbach, MA and Braun, J and Xavier, RJ and Clish, CB and Li, H and Bushman, FD and Lewis, JD and Wu, GD}, title = {Role of dietary fiber in the recovery of the human gut microbiome and its metabolome.}, journal = {Cell host &amp; microbe}, volume = {29}, number = {3}, pages = {394-407.e5}, pmid = {33440171}, issn = {1934-6069}, support = {P30 DK040561/DK/NIDDK NIH HHS/United States ; P30 DK043351/DK/NIDDK NIH HHS/United States ; P01 HL147823/HL/NHLBI NIH HHS/United States ; P30 DK050306/DK/NIDDK NIH HHS/United States ; UL1 TR000003/TR/NCATS NIH HHS/United States ; UG3 DA050306/DA/NIDA NIH HHS/United States ; }, mesh = {Amino Acids ; Bacteria/metabolism ; Diet ; *Dietary Fiber ; Enteral Nutrition ; Feces/microbiology ; Firmicutes/metabolism ; Gastrointestinal Microbiome/genetics/*physiology ; Humans ; Metabolome ; Vegans ; }, abstract = {Gut microbiota metabolites may be important for host health, yet few studies investigate the correlation between human gut microbiome and production of fecal metabolites and their impact on the plasma metabolome. Since gut microbiota metabolites are influenced by diet, we performed a longitudinal analysis of the impact of three divergent diets, vegan, omnivore, and a synthetic enteral nutrition (EEN) diet lacking fiber, on the human gut microbiome and its metabolome, including after a microbiota depletion intervention. Omnivore and vegan, but not EEN, diets altered fecal amino acid levels by supporting the growth of Firmicutes capable of amino acid metabolism. This correlated with relative abundance of a sizable number of fecal amino acid metabolites, some not previously associated with the gut microbiota. The effect on the plasma metabolome, in contrast, were modest. The impact of diet, particularly fiber, on the human microbiome influences broad classes of metabolites that may modify health.}, }
@article {pmid33439913, year = {2021}, author = {Lee, YT and Mohd Ismail, NI and Wei, LK}, title = {Microbiome and ischemic stroke: A systematic review.}, journal = {PloS one}, volume = {16}, number = {1}, pages = {e0245038}, pmid = {33439913}, issn = {1932-6203}, mesh = {Bacteroidetes/isolation &amp; purification ; Fatty Acids, Volatile/*metabolism ; Firmicutes/isolation &amp; purification ; Humans ; Ischemic Stroke/metabolism/*microbiology ; Microbiota/*physiology ; }, abstract = {BACKGROUND: Ischemic stroke is one of the non-communicable diseases that contribute to the significant number of deaths worldwide. However, the relationship between microbiome and ischemic stroke remained unknown. Hence, the objective of this study was to perform systematic review on the relationship between human microbiome and ischemic stroke.<br><br>METHODS: A systematic review on ischemic stroke was carried out for all articles obtained from databases until 22nd October 2020. Main findings were extracted from all the eligible studies.<br><br>RESULTS: Eighteen eligible studies were included in the systematic review. These studies suggested that aging, inflammation, and different microbial compositions could contribute to ischemic stroke. Phyla Firmicutes and Bacteroidetes also appeared to manipulate post-stroke outcome. The important role of microbiota-derived short-chain fatty acids and trimethylamine N-oxide in ischemic stroke were also highlighted.<br><br>CONCLUSIONS: This is the first systematic review that investigates the relationship between microbiome and ischemic stroke. Aging and inflammation contribute to differential microbial compositions and predispose individuals to ischemic stroke.}, }
@article {pmid33436217, year = {2021}, author = {Elshahed, MS and Miron, A and Aprotosoaie, AC and Farag, MA}, title = {Pectin in diet: Interactions with the human microbiome, role in gut homeostasis, and nutrient-drug interactions.}, journal = {Carbohydrate polymers}, volume = {255}, number = {}, pages = {117388}, doi = {10.1016/j.carbpol.2020.117388}, pmid = {33436217}, issn = {1879-1344}, mesh = {Animals ; Bacteroidetes/genetics/immunology ; Biotransformation ; Clinical Trials as Topic ; Diet/methods ; Fatty Acids, Volatile/biosynthesis ; Fermentation ; Firmicutes/genetics/immunology ; Gastrointestinal Microbiome/*immunology ; Homeostasis/*immunology ; Humans ; Immunomodulation/*physiology ; Pectins/immunology/metabolism/*pharmacology ; Polysaccharides/*administration &amp; dosage/analysis ; Prebiotics/*administration &amp; dosage/analysis ; }, abstract = {Pectins are a part of daily diet as well as food additives that are indigestible polysaccharides by human enzymes, however, they can be easily degraded by gut bacteria with the production of short chain fatty acids (SCFAs). Knowledge of pectin gut homeostasis and further how pectin affect gut bacterial communities is insufficient and limited. This review focuses on providing the whole story of how pectin functions as prebiotics in the gut. Understanding the interplay between functional and immunological responses inside animal or human gut as influenced by pectin in diets is provided. The interaction between pectin and gut microbiota is presented from both sides, in terms of how pectin affects gut microbiome and or the fermentation products produced in response by gut bacteria. This knowledge can be used to define preferred dietary pectins, targeting beneficial bacteria, and favoring balanced microbiota communities in the gut to maximize pectins' health benefits.}, }
@article {pmid33436213, year = {2021}, author = {Hövels, M and Kosciow, K and Deppenmeier, U}, title = {Characterization of a novel endo-levanase from Azotobacter chroococcum DSM 2286 and its application for the production of prebiotic fructooligosaccharides.}, journal = {Carbohydrate polymers}, volume = {255}, number = {}, pages = {117384}, doi = {10.1016/j.carbpol.2020.117384}, pmid = {33436213}, issn = {1879-1344}, mesh = {Azotobacter/*enzymology/genetics ; Bacterial Proteins/genetics/*metabolism ; Disaccharides/chemistry/metabolism ; Escherichia coli/enzymology/genetics ; Fructans/chemistry/metabolism ; Fructose/chemistry/metabolism ; Gene Expression ; Gluconobacter/*enzymology/genetics ; Glycoside Hydrolases/genetics/*metabolism ; Hexosyltransferases/genetics/*metabolism ; Humans ; Hydrolysis ; Oligosaccharides/*biosynthesis/chemistry ; Phleum/chemistry ; Prebiotics/*analysis ; Recombinant Proteins/genetics/metabolism ; Sucrose/chemistry/metabolism ; }, abstract = {Prebiotics are known for their ability to modulate the composition of the human microbiome and mediate health-promoting benefits. Endo-levanases, which hydrolyze levan into short-chain FOS, could be used for the production of levan-based prebiotics. The novel endo-levanase (LevB2286) from Azotobacter chroococcum DSM 2286, combines an exceptionally high specific activity with advantageous hydrolytic properties. Starting from levan isolated from Timothy grass, LevB2286 produced FOS ranging from DP 2 - 8. In contrast to endo-levanases described in the literature, LevB2286 formed minor amounts of fructose and levanbiose, even with greatly extended incubation. The combined activity of LevB2286 and the levansucrase LevS1417 from Gluconobacter japonicus LMG 1417 led to a one-step synthesis of levan-type FOS from sucrose. 387.4 ± 17.3 g L[-1] FOS were produced within 48 h by the production strategy based on crude cell extract of recombinant Escherichia coli expressing levS1417 and levB2286 simultaneously.}, }
@article {pmid33436100, year = {2021}, author = {Silverstein, RB and Mysorekar, IU}, title = {Group therapy on in utero colonization: seeking common truths and a way forward.}, journal = {Microbiome}, volume = {9}, number = {1}, pages = {7}, pmid = {33436100}, issn = {2049-2618}, support = {R01 HD091218/HD/NICHD NIH HHS/United States ; }, mesh = {*Consensus ; Female ; Fetus/*microbiology ; Humans ; Microbiota/*physiology ; Uncertainty ; Uterus/*microbiology ; }, abstract = {The human microbiome refers to the genetic composition of microorganisms in a particular location in the human body. Emerging evidence over the past many years suggests that the microbiome constitute drivers of human fate almost at par with our genome and epigenome. It is now well accepted after decades of disbelief that a broad understanding of human development, health, physiology, and disease requires understanding of the microbiome along with the genome and epigenome. We are learning daily of the interdependent relationships between microbiome/microbiota and immune responses, mood, cancer progression, response to therapies, aging, obesity, antibiotic usage, and overusage and much more. The next frontier in microbiome field is understanding when does this influence begin? Does the human microbiome initiate at the time of birth or are developing human fetuses already primed with microbes and their products in utero. In this commentary, we reflect on evidence gathered thus far on this question and identify the unknown common truths. We present a way forward to continue understanding our microbial colleagues and our interwoven fates.}, }
@article {pmid33435848, year = {2021}, author = {Sanders, D and Grunden, A and Dunn, RR}, title = {A review of clothing microbiology: the history of clothing and the role of microbes in textiles.}, journal = {Biology letters}, volume = {17}, number = {1}, pages = {20200700}, pmid = {33435848}, issn = {1744-957X}, support = {T32 GM008776/GM/NIGMS NIH HHS/United States ; T32 GM133366/GM/NIGMS NIH HHS/United States ; }, mesh = {Clothing ; Humans ; *Laundering ; *Microbiota ; Textiles ; }, abstract = {Humans have worn clothing for thousands of years, and since its invention, clothing has evolved from its simple utilitarian function for survival to become an integral part of society. While much consideration has been given to the broad environmental impacts of the textile and laundering industries, little is known about the impact wearing clothing has had on the human microbiome, particularly that of the skin, despite our long history with clothing. This review discusses the history of clothing and the evolution of textiles, what is and is not known about microbial persistence on and degradation of various fibres, and what opportunities for the industrial and environmental application of clothing microbiology exist for the future.}, }
@article {pmid33428723, year = {2021}, author = {Laursen, MF and Bahl, MI and Licht, TR}, title = {Settlers of our inner surface - factors shaping the gut microbiota from birth to toddlerhood.}, journal = {FEMS microbiology reviews}, volume = {45}, number = {4}, pages = {}, pmid = {33428723}, issn = {1574-6976}, support = {NNF19OC0056246//Novo Nordic Foundation/ ; }, mesh = {Adult ; *Gastrointestinal Microbiome ; Humans ; *Microbiota ; }, abstract = {During the first 3 years of life, the microbial ecosystem within the human gut undergoes a process that is unlike what happens in this ecosystem at any other time of our life. This period in time is considered a highly important developmental window, where the gut microbiota is much less resilient and much more responsive to external and environmental factors than seen in the adult gut. While advanced bioinformatics and clinical correlation studies have received extensive focus within studies of the human microbiome, basic microbial growth physiology has attracted much less attention, although it plays a pivotal role to understand the developing gut microbiota during early life. In this review, we will thus take a microbial ecology perspective on the analysis of factors that influence the temporal development of the infant gut microbiota. Such factors include sources of microbes that seed the intestinal environment, physico-chemical (abiotic) conditions influencing microbial growth and the availability of nutrients needed by the intestinal microbes.}, }
@article {pmid33428498, year = {2021}, author = {Koidl, L and Untersmayr, E}, title = {The clinical implications of the microbiome in the development of allergy diseases.}, journal = {Expert review of clinical immunology}, volume = {17}, number = {2}, pages = {115-126}, doi = {10.1080/1744666X.2021.1874353}, pmid = {33428498}, issn = {1744-8409}, mesh = {Adaptive Immunity ; Asthma/immunology/microbiology ; Dermatitis, Atopic/immunology/microbiology ; Drug Hypersensitivity/immunology/microbiology ; Food Hypersensitivity/immunology/microbiology ; Gastrointestinal Microbiome/immunology/physiology ; Humans ; *Hypersensitivity/immunology/microbiology ; Immunity, Innate ; *Microbiota/immunology/physiology ; Respiratory System/immunology/microbiology ; Rhinitis, Allergic/immunology/microbiology ; Skin/immunology/microbiology ; }, abstract = {Introduction: A substantial number of patients worldwide are affected by allergies. Emerging evidence suggests that the individual microbial composition might contribute to the development of allergies or might even protect from allergic diseases.Areas covered: This review provides a detailed summary regarding available knowledge on the composition of a healthy human microbiome at allergy relevant body sites. It highlights factors influencing the microbiota composition. Furthermore, recent findings on the mutual interaction of the microbiota with the innate and adaptive immune system are reported. In the final part, this knowledge is combined to discuss microbial implications for food allergy, allergic asthma, allergic rhinitis, and skin allergies. Literature for this review was gathered by searching PubMed and Google Scholar databases between October and December 2020.Expert opinion: Due to the highly individual composition, it is currently not possible to define the characteristics of a site-specific microbiome in health and disease. Mainly effects of bacterial communities have been investigated, while fungal or viral influences are not yet well understood. The communication between microbial communities found in different organs impact on allergy development. Thus, a personalized approach is essential to beneficially influence these complex interactions and to modulate the host-specific microbiota in allergies.}, }
@article {pmid33425774, year = {2020}, author = {Campbell, PM and Humphreys, GJ and Summers, AM and Konkel, JE and Knight, CG and Augustine, T and McBain, AJ}, title = {Does the Microbiome Affect the Outcome of Renal Transplantation?.}, journal = {Frontiers in cellular and infection microbiology}, volume = {10}, number = {}, pages = {558644}, pmid = {33425774}, issn = {2235-2988}, support = {21927/VAC_/Versus Arthritis/United Kingdom ; 2102580/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Humans ; Immunosuppression Therapy ; *Kidney Failure, Chronic/surgery ; *Kidney Transplantation ; *Microbiota ; *Renal Insufficiency, Chronic ; }, abstract = {The role of the human microbiome in health and disease is becoming increasingly apparent. Emerging evidence suggests that the microbiome is affected by solid organ transplantation. Kidney transplantation is the gold standard treatment for End-Stage Renal Disease (ESRD), the advanced stage of Chronic Kidney Disease (CKD). The question of how ESRD and transplantation affect the microbiome and vice versa includes how the microbiome is affected by increased concentrations of toxins such as urea and creatinine (which are elevated in ESRD), whether restoration of renal function following transplantation alters the composition of the microbiome, and the impact of lifelong administration of immunosuppressive drugs on the microbiome. Changes in microbiome composition and activity have been reported in ESRD and in therapeutic immunosuppression, but the effect on the outcome of transplantation is not well-understood. Here, we consider the current evidence that changes in kidney function and immunosuppression following transplantation influence the oral, gut, and urinary microbiomes in kidney transplant patients. The potential for changes in these microbiomes to lead to disease, systemic inflammation, or rejection of the organ itself is discussed, along with the possibility that restoration of kidney function might re-establish orthobiosis.}, }
@article {pmid33424043, year = {2021}, author = {Yu, L}, title = {Restoring Good Health in Elderly with Diverse Gut Microbiome and Food Intake Restriction to Combat COVID-19.}, journal = {Indian journal of microbiology}, volume = {61}, number = {1}, pages = {104-107}, pmid = {33424043}, issn = {0046-8991}, abstract = {COVID-19 continues to be an ongoing global threat. The elderly with underlying health conditions like cardiovascular and lung diseases, diabetes, obesity, are the most vulnerable to this disease. Curing the pre-existing health conditions will greatly increase a person's resilience to COVID-19 and lower the death rate of the old people. Digestion and immunity form an integrated nutrition acquisition process, especially in obtaining essential amino acids and essential fatty acids from living microbial cells. A mature strong immunity coupled with gut dysbiosis in adults is the main cause of nutritional disorders like morbid obesity, diabetes mellitus, cardiovascular and pulmonary diseases. Nutrition disorders in return worsen dysbiosis. Human microbiome has an intrinsic duality. While a diverse microbiome provides a full spectrum of essential nutrients to our body, nutrition disorders fuel overgrowth of microbiota (dysbiosis) at many sites on or inside our body, and are the main causes of chronic inflammation at these sites. In the case of COVID-19, nutritional disorder impairs the immunity, causes hyperinflammation, and leads to the protracted overload of cytokines by the immune system, i.e., the cytokine storm. Autophagy induced by restrictive eating is an ideal inhibitor of microbiota overgrowth, as autophagy deprives microbiota of excessive nutrition for replication. Autophagy also attenuates inflammation. Therefore, as a precaution, the author suggests restoring good health in the elderly with the support from a diverse gut microbiome and daily regular food intake restriction, so as to lower the risk of developing into severe case even if they are infected by COVID-19.}, }
@article {pmid33422623, year = {2022}, author = {Pineider, J and Reisch, J and Harris-Tryon, T and Savory, S}, title = {Knowledge and attitude toward the human microbiome: A single-center cross-sectional survey.}, journal = {Journal of the American Academy of Dermatology}, volume = {86}, number = {1}, pages = {165-167}, doi = {10.1016/j.jaad.2020.12.078}, pmid = {33422623}, issn = {1097-6787}, mesh = {Cross-Sectional Studies ; *Health Knowledge, Attitudes, Practice ; Humans ; *Microbiota ; Surveys and Questionnaires ; }, }
@article {pmid33417041, year = {2021}, author = {Tytgat, HLP and Rasinkangas, P and Ritari, J and Reunanen, J and Aalvink, S and Lin, CW and Palva, A and Douillard, FP and de Vos, WM}, title = {Selection and characterization of a SpaCBA pilus-secreting food-grade derivative of Lacticaseibacillus rhamnosus GG.}, journal = {Applied microbiology and biotechnology}, volume = {105}, number = {3}, pages = {1123-1131}, pmid = {33417041}, issn = {1432-0614}, support = {250172//FP7 Ideas: European Research Council/ ; 252123//Academy of Finland/ ; 299749//Academy of Finland/ ; 137389//Academy of Finland/ ; SIAM Gravity Grant 024.002.002//Nederlandse Organisatie voor Wetenschappelijk Onderzoek/ ; Spinoza//Nederlandse Organisatie voor Wetenschappelijk Onderzoek/ ; }, mesh = {Bacterial Proteins/genetics ; Fimbriae Proteins ; Fimbriae, Bacterial/genetics ; Humans ; *Lacticaseibacillus rhamnosus/genetics ; Mucus ; *Probiotics ; }, abstract = {Many studies have established the functional properties of Lacticaseibacillus rhamnosus GG, previously known as Lactobacillus rhamnosus GG, marketed worldwide as a probiotic. The extraordinary capacity of L. rhamnosus GG to bind to human mucus and influence the immune system especially stand out. Earlier, we have shown the key role of its SpaCBA sortase-dependent pili encoded by the spaCBA-srtC1 gene cluster herein. These heterotrimeric pili consist of a shaft pilin SpaA, a basal pilin SpaB, and tip pilin SpaC that contains a mucus-binding domain. Here, we set out to characterize a food-grade non-GMO mutant of L. rhamnosus GG, strain PA11, which secretes its pilins, rather than coupling them to the cell surface, due to a defect in the housekeeping sortase A. The sortase-negative strain PA11 was extensively characterized using functional genomics and biochemical approaches and found to secrete the SpaCBA pili into the supernatant. Given the functional importance and uniqueness of the mucus-binding pili of L. rhamnosus GG, strain PA11 offers novel opportunities towards the characterization and further therapeutic application of SpaCBA pili and their low-cost, large-scale production. KEY POINTS: •Creation of pilus-secreting mutant (PA11) of the key probiotic LGG. •Strain PA11 is defective in a functional housekeeping sortase SrtA. •Strain PA11 opens novel biotherapeutic application avenues. Graphical abstract.}, }
@article {pmid33410935, year = {2021}, author = {Li, W and Nelson, KE}, title = {Microbial Species that Initially Colonize the Human Gut at Birth or in Early Childhood Can Stay in Human Body for Lifetime.}, journal = {Microbial ecology}, volume = {82}, number = {4}, pages = {1074-1079}, pmid = {33410935}, issn = {1432-184X}, mesh = {Adult ; Child, Preschool ; *Gastrointestinal Microbiome/genetics ; *Human Body ; Humans ; Infant, Newborn ; Metagenome ; Metagenomics ; Twins, Dizygotic/genetics ; }, abstract = {In recent years, many studies have described the composition and function of the human microbiome at different body sites and suggested a role for the microbiome in various diseases and health conditions. Some studies, using longitudinal samples, have also suggested how the microbiome changes over time due to disease, diet, development, travel, and other environmental factors. However, to date, no study has demonstrated whether the microorganisms established at birth or in early childhood, either transmitted from parents or obtained from the environment, can stay in the human body until adult or senior age. To directly answer this question is difficult, because microbiome samples at childhood and at later adulthood for the same individual will need to be compared and the field is not old enough to have allowed for that type of sample collection. Here, using a metagenomic approach, we analyzed 1004 gut microbiome samples from senior adults (65 ± 7.8 years) from the TwinsUK cohort. Our data indicate that many species in the human gut acquired in early childhood can stay for a lifetime until senior ages. We identified the rare genomic variants (single nucleotide variation and indels) for 27 prevalent species with enough sequencing coverage for confident genomic variant identification. We found that for some species, twin pairs, including both monozygotic (MZ) and dizygotic (DZ) twins, share significantly more rare variants than unrelated subject pairs. But no significant difference is found between MZ and DZ twin pairs. These observations strongly suggest that these species acquired in early childhood remained in these persons until senior adulthood.}, }
@article {pmid33407112, year = {2021}, author = {Jing, G and Zhang, Y and Cui, W and Liu, L and Xu, J and Su, X}, title = {Meta-Apo improves accuracy of 16S-amplicon-based prediction of microbiome function.}, journal = {BMC genomics}, volume = {22}, number = {1}, pages = {9}, pmid = {33407112}, issn = {1471-2164}, support = {31771463//National Natural Science Foundation of China (CN)/ ; ZR201807060158//Natural Science Foundation of Shandong Province/ ; 2018M630807//China Postdoctoral Science Foundation/ ; 32070086//National Natural Science Foundation of China/ ; 32000389//National Natural Science Foundation of China/ ; }, mesh = {*Bacteria/genetics ; Metagenome ; Metagenomics ; *Microbiota/genetics ; RNA, Ribosomal, 16S/genetics ; }, abstract = {BACKGROUND: Due to their much lower costs in experiment and computation than metagenomic whole-genome sequencing (WGS), 16S rRNA gene amplicons have been widely used for predicting the functional profiles of microbiome, via software tools such as PICRUSt 2. However, due to the potential PCR bias and gene profile variation among phylogenetically related genomes, functional profiles predicted from 16S amplicons may deviate from WGS-derived ones, resulting in misleading results.<br><br>RESULTS: Here we present Meta-Apo, which greatly reduces or even eliminates such deviation, thus deduces much more consistent diversity patterns between the two approaches. Tests of Meta-Apo on >&#x2009;5000 16S-rRNA amplicon human microbiome samples from 4 body sites showed the deviation between the two strategies is significantly reduced by using only 15 WGS-amplicon training sample pairs. Moreover, Meta-Apo enables cross-platform functional comparison between WGS and amplicon samples, thus greatly improve 16S-based microbiome diagnosis, e.g. accuracy of gingivitis diagnosis via 16S-derived functional profiles was elevated from 65 to 95% by WGS-based classification. Therefore, with the low cost of 16S-amplicon sequencing, Meta-Apo can produce a reliable, high-resolution view of microbiome function equivalent to that offered by shotgun WGS.<br><br>CONCLUSIONS: This suggests that large-scale, function-oriented microbiome sequencing projects can probably benefit from the lower cost of 16S-amplicon strategy, without sacrificing the precision in functional reconstruction that otherwise requires WGS. An optimized C++ implementation of Meta-Apo is available on GitHub (https://github.com/qibebt-bioinfo/meta-apo) under a GNU GPL license. It takes the functional profiles of a few paired WGS:16S-amplicon samples as training, and outputs the calibrated functional profiles for the much larger number of 16S-amplicon samples.}, }
@article {pmid33406974, year = {2021}, author = {Clements, TW and Tolonen, M and Ball, CG and Kirkpatrick, AW}, title = {Secondary Peritonitis and Intra-Abdominal Sepsis: An Increasingly Global Disease in Search of Better Systemic Therapies.}, journal = {Scandinavian journal of surgery : SJS : official organ for the Finnish Surgical Society and the Scandinavian Surgical Society}, volume = {110}, number = {2}, pages = {139-149}, doi = {10.1177/1457496920984078}, pmid = {33406974}, issn = {1799-7267}, mesh = {Abdomen ; Critical Care ; *Gastrointestinal Diseases ; Humans ; *Peritonitis/etiology/therapy ; *Sepsis/diagnosis/etiology/therapy ; }, abstract = {Secondary peritonitis and intra-abdominal sepsis are a global health problem. The life-threatening systemic insult that results from intra-abdominal sepsis has been extensively studied and remains somewhat poorly understood. While local surgical therapy for perforation of the abdominal viscera is an age-old therapy, systemic therapies to control the subsequent systemic inflammatory response are scarce. Advancements in critical care have led to improved outcomes in secondary peritonitis. The understanding of the effect of secondary peritonitis on the human microbiome is an evolving field and has yielded potential therapeutic targets. This review of secondary peritonitis discusses the history, classification, pathophysiology, diagnosis, treatment, and future directions of the management of secondary peritonitis. Ongoing clinical studies in the treatment of secondary peritonitis and the open abdomen are discussed.}, }
@article {pmid33395654, year = {2020}, author = {Kakabadze, E and Grdzelishvili, N and Sanikidze, L and Makalatia, K and Chanishvili, N}, title = {REVIVAL OF MICROBIAL THERAPEUTICS, WITH EMPHASIS ON PROBIOTIC LACTOBACILLUS (REVIEW).}, journal = {Georgian medical news}, volume = {}, number = {308}, pages = {129-134}, pmid = {33395654}, issn = {1512-0112}, mesh = {Dysbiosis/therapy ; Humans ; Lactobacillus ; *Microbiota ; *Probiotics/therapeutic use ; }, abstract = {The idea to use living microorganisms for disease prevention and treatment was introduced a century ago, but yet the full potential and benefits of microbial therapeutics has not been entirely understood. In the light of developments of human microbiome studies, probiotics are gaining new momentum, where health benefit conferring by Lactobacillus are emerging as one of the novel approaches in the treatment and prophylactics of dysbiosis. The present review focuses on the origin and development of the probiotic's concept, mechanisms of action and anticipated use of probiotic Lactobacillus as well as of microbial therapeutics. The required regulatory frameworks associated with probiotic use and marketing are discussed.}, }
@article {pmid33383954, year = {2020}, author = {D'Onofrio, V and Del Chierico, F and Belci, P and Vernocchi, P and Quagliariello, A and Reddel, S and Conta, G and Mancino, MV and Fadda, M and Scigliano, MC and Morelli, R and De Francesco, A and Guagnini, F and Fassio, F and Galletti, R and Putignani, L}, title = {Effects of a Synbiotic Formula on Functional Bowel Disorders and Gut Microbiota Profile during Long-Term Home Enteral Nutrition (LTHEN): A Pilot Study.}, journal = {Nutrients}, volume = {13}, number = {1}, pages = {}, pmid = {33383954}, issn = {2072-6643}, support = {RC 201905_Genetica_Putignani//Ministry of Health, Italy/ ; -//Allergy Therapeutics Italia/ ; }, mesh = {Aged ; Biodiversity ; Constipation ; Dysbiosis ; *Enteral Nutrition ; Fatty Acids, Volatile ; Feces/microbiology ; Female ; *Food, Formulated ; *Gastrointestinal Microbiome ; Humans ; *Irritable Bowel Syndrome/microbiology ; Italy ; Male ; Pilot Projects ; Prebiotics ; Probiotics ; Surveys and Questionnaires ; Synbiotics ; }, abstract = {Long-term enteral nutrition (LTEN) can induce gut microbiota (GM) dysbiosis and gastrointestinal related symptoms, such as constipation or diarrhoea. To date, the treatment of constipation is based on the use of laxatives and prebiotics. Only recently have probiotics and synbiotics been considered, the latter modulating the GM and regulating intestinal functions. This randomized open-label intervention study evaluated the effects of synbiotic treatment on the GM profile, its functional activity and on intestinal functions in long-term home EN (LTHEN) patients. Twenty LTHEN patients were recruited to take enteral formula plus one sachet/day of synbiotic (intervention group, IG) or enteral formula (control group, CG) for four months and evaluated for constipation, stool consistency, and GM and metabolite profiles. In IG patients, statistically significant reduction of constipation and increase of stool consistency were observed after four months (T1), compared to CG subjects. GM ecology analyses revealed a decrease in the microbial diversity of both IC and CG groups. Biodiversity increased at T1 for 5/11 IG patients and Methanobrevibacter was identified as the biomarker correlated to the richness increase. Moreover, the increase of short chain fatty acids and the reduction of harmful molecules have been correlated to synbiotic administration. Synbiotics improve constipation symptoms and influences Methanobrevibacter growth in LTHEN patients.}, }
@article {pmid33382980, year = {2021}, author = {Dohlman, AB and Arguijo Mendoza, D and Ding, S and Gao, M and Dressman, H and Iliev, ID and Lipkin, SM and Shen, X}, title = {The cancer microbiome atlas: a pan-cancer comparative analysis to distinguish tissue-resident microbiota from contaminants.}, journal = {Cell host &amp; microbe}, volume = {29}, number = {2}, pages = {281-298.e5}, pmid = {33382980}, issn = {1934-6069}, support = {R35 GM122465/GM/NIGMS NIH HHS/United States ; P30 CA014236/CA/NCI NIH HHS/United States ; R01 DK113136/DK/NIDDK NIH HHS/United States ; R01 DK119795/DK/NIDDK NIH HHS/United States ; U01 CA214300/CA/NCI NIH HHS/United States ; }, mesh = {Artifacts ; Bacteria/classification/*genetics ; Chromosome Mapping ; Decontamination/methods ; Gastrointestinal Microbiome/*genetics ; Gastrointestinal Neoplasms/*genetics/microbiology ; Gastrointestinal Tract/*microbiology/pathology ; Genetic Markers/genetics ; High-Throughput Nucleotide Sequencing ; Humans ; }, abstract = {Studying the microbial composition of internal organs and their associations with disease remains challenging due to the difficulty of acquiring clinical biopsies. We designed a statistical model to analyze the prevalence of species across sample types from The Cancer Genome Atlas (TCGA), revealing that species equiprevalent across sample types are predominantly contaminants, bearing unique signatures from each TCGA-designated sequencing center. Removing such species mitigated batch effects and isolated the tissue-resident microbiome, which was validated by original matched TCGA samples. Gene copies and nucleotide variants can further distinguish mixed-evidence species. We, thus, present The Cancer Microbiome Atlas (TCMA), a collection of curated, decontaminated microbial compositions of oropharyngeal, esophageal, gastrointestinal, and colorectal tissues. This led to the discovery of prognostic species and blood signatures of mucosal barrier injuries and enabled systematic matched microbe-host multi-omic analyses, which will help guide future studies of the microbiome's role in human health and disease.}, }
@article {pmid33377531, year = {2021}, author = {Fang, C and Wu, L and Zhu, C and Xie, WZ and Hu, H and Zeng, XT}, title = {A potential therapeutic strategy for prostatic disease by targeting the oral microbiome.}, journal = {Medicinal research reviews}, volume = {41}, number = {3}, pages = {1812-1834}, pmid = {33377531}, issn = {1098-1128}, mesh = {Humans ; Male ; *Microbiota ; *Prostatic Diseases ; *Prostatic Neoplasms ; }, abstract = {Nowadays, human microbiome research is rapidly growing and emerging evidence has witnessed the critical role that oral microbiome plays in the process of human health and disease. Oral microbial dysbiosis has been confirmed as a contributory cause for diseases in multiple body systems, ranging from the oral cavity to the gastrointestinal, endocrine, immune, cardiovascular, and even nervous system. As research progressing, oral microbiome-based diagnosis and therapy are proposed and applied, which may represent potential drug targets in systemic diseases. Recent studies have uncovered the possible association between periodontal disease and prostatic disease, suggesting new prevention and therapeutic treatment for the disease by targeting periodontal pathogens. Thus, we performed this review to first explore the association between the oral microbiome and prostatic disease, according to current knowledge based on published articles, and then mainly focus on the underlying molecular and cellular mechanisms and the potential prevention and treatment derived from these mechanistic studies.}, }
@article {pmid33372204, year = {2021}, author = {Turunen, KA and Kantele, A and , }, title = {Revisiting travellers' diarrhoea justifying antibiotic treatment: prospective study.}, journal = {Journal of travel medicine}, volume = {28}, number = {3}, pages = {}, doi = {10.1093/jtm/taaa237}, pmid = {33372204}, issn = {1708-8305}, mesh = {*Anti-Bacterial Agents/therapeutic use ; Bacterial Physiological Phenomena ; *Diarrhea/drug therapy/microbiology ; Humans ; Prospective Studies ; Risk Factors ; *Travel-Related Illness ; }, abstract = {BACKGROUND: As antimicrobials increase the risk of acquiring multidrug-resistant (MDR) bacteria, unnecessary antibiotics should be avoided for travellers' diarrhoea (TD). Antibiotics are recommended in TD accompanied by fever or incapacitation (TD justifying use of antibiotics, TDjuAB). Seeking tools for reducing antibiotic use, we explored factors predisposing to TDjuAB and scrutinized antibiotic treatment among those with TDjuAB [TDjuAB(+) subgroup] and those with diarrhoea not justifying antibiotics [TDjuAB(-) subgroup].<br><br>METHODS: We conducted a study among 370 prospectively recruited visitors to the tropics. Stool samples and questionnaires were collected before and after travel. Enteric pathogens were analysed by qPCR for enteropathogenic (EPEC), enteroaggregative (EAEC), enterotoxigenic (ETEC), enterohaemorrhagic (EHEC) and enteroinvasive (EIEC) E. coli/Shigella, Campylobacter, Salmonella, Yersinia and Vibrio cholerae, and for ETEC's toxins LT (heat-labile), STh (human heat-stable) and STp (porcine heat-stable). TD was defined by the WHO criteria and TDjuAB as diarrhoea accompanied by fever, and/or disrupting or preventing daily activities. Multivariable analysis was applied-separately for travel-related factors and pathogens-to identify risk factors for TDjuAB(+).<br><br>RESULTS: Among the 370 travellers, TD was contracted by 253 (68%), categorized as TDjuAB(+) in 93/253 (37%) and TDjuAB(-) in 160/253 (63%) of the cases. Antibiotics were used for TD by 41% in TDjuAB(+) and by 7% in the TDjuAB(-) group. Relative risk ratios (RRR)s are presented for both the TDjuAB(+) and the TDjuAB(-) groups. TDjuAB(+) was associated with long travel duration and young age. Among the 298 subjects not having taken antibiotics, increased RRRs were found e.g. for findings of Campylobacter coli/jejuni and ETEC's STh toxin.<br><br>CONCLUSIONS: The first to analyse risk factors for TDjuAB, our study presents RRRs for demographic and behavioural factors and for various pathogens. Only less than half of those in the TDjuAB(+) group took antibiotics, which demonstrates that most cases meeting the current criteria recover without antimicrobial treatment.}, }
@article {pmid33367793, year = {2021}, author = {Handa, S and Reyna, A and Wiryaman, T and Ghosh, P}, title = {Determinants of adenine-mutagenesis in diversity-generating retroelements.}, journal = {Nucleic acids research}, volume = {49}, number = {2}, pages = {1033-1045}, pmid = {33367793}, issn = {1362-4962}, support = {R01 GM132720/GM/NIGMS NIH HHS/United States ; }, mesh = {*Adenine/chemistry ; Arginine/chemistry ; Bacteriophages/*genetics ; Base Sequence ; Bordetella/virology ; Catalysis ; Cell-Free System ; Computer Simulation ; DNA, Complementary/genetics ; Glycine/chemistry ; High-Throughput Nucleotide Sequencing ; Models, Molecular ; *Mutagenesis ; Protein Conformation ; RNA-Directed DNA Polymerase/metabolism ; Recombinant Proteins/metabolism ; Retroelements/*genetics ; }, abstract = {Diversity-generating retroelements (DGRs) vary protein sequences to the greatest extent known in the natural world. These elements are encoded by constituents of the human microbiome and the microbial 'dark matter'. Variation occurs through adenine-mutagenesis, in which genetic information in RNA is reverse transcribed faithfully to cDNA for all template bases but adenine. We investigated the determinants of adenine-mutagenesis in the prototypical Bordetella bacteriophage DGR through an in vitro system composed of the reverse transcriptase bRT, Avd protein, and a specific RNA. We found that the catalytic efficiency for correct incorporation during reverse transcription by the bRT-Avd complex was strikingly low for all template bases, with the lowest occurring for adenine. Misincorporation across a template adenine was only somewhat lower in efficiency than correct incorporation. We found that the C6, but not the N1 or C2, purine substituent was a key determinant of adenine-mutagenesis. bRT-Avd was insensitive to the C6 amine of adenine but recognized the C6 carbonyl of guanine. We also identified two bRT amino acids predicted to nonspecifically contact incoming dNTPs, R74 and I181, as promoters of adenine-mutagenesis. Our results suggest that the overall low catalytic efficiency of bRT-Avd is intimately tied to its ability to carry out adenine-mutagenesis.}, }
@article {pmid33359433, year = {2021}, author = {Lääveri, T and Antikainen, J and Mero, S and Pakkanen, SH and Kirveskari, J and Roivainen, M and Kantele, A}, title = {Bacterial, viral and parasitic pathogens analysed by qPCR: Findings from a prospective study of travellers' diarrhoea.}, journal = {Travel medicine and infectious disease}, volume = {40}, number = {}, pages = {101957}, doi = {10.1016/j.tmaid.2020.101957}, pmid = {33359433}, issn = {1873-0442}, mesh = {Animals ; *Cryptosporidiosis ; *Cryptosporidium ; Diarrhea ; Escherichia coli ; Feces ; Humans ; *Parasites ; Prospective Studies ; }, abstract = {BACKGROUND: The diagnostics of travellers' diarrhoea (TD) has been revolutionised by multiplex qPCR assays. While mostly of bacterial aetiology, viruses and parasites account for the disease among 10-20% of travellers. Despite this, prospective studies applying qPCR assays remain scarce that cover not only bacteria, such as the various diarrhoeagenic Escherichia coli (DEC), but also viral and parasitic pathogens.<br><br>METHOD: We analysed by qPCR pre- and post-travel stool samples of 146 Finnish travellers for bacterial, viral and parasitic pathogens: enteropathogenic (EPEC), enteroaggregative (EAEC), enterotoxigenic (ETEC), enterohaemorrhagic (EHEC), and enteroinvasive (EIEC) E. coli; Shigella, Campylobacter, Salmonella, Yersinia and Vibrio cholerae; norovirus G1 and G2, rotavirus, enteroviruses, and sapovirus; and Giardia lamblia, Entamoeba histolytica, and Cryptosporidium. Symptoms and medication data during travel were collected by questionnaires.<br><br>RESULTS: We detected bacterial pathogens in 102/146 samples (69.9%; EAEC, EPEC, ETEC most common), viral ones in 13 (8.9%; norovirus most common), and parasitic ones in one (0.7%; Giardia). Noroviruses were associated with severe symptoms (23.5% versus non-severe 4.9%). In the TD group, 41.7% (5/12) of those with viral pathogens (vs. 13.3%; 11/83 without) took antibiotics.<br><br>CONCLUSION: Viral pathogens, particularly noroviruses, prevail in severe TD. The symptoms of viral disease are often severe and lead to unwarranted use of antibiotics.}, }
@article {pmid33356857, year = {2021}, author = {Van Ende, M and Timmermans, B and Vanreppelen, G and Siscar-Lewin, S and Fischer, D and Wijnants, S and Romero, CL and Yazdani, S and Rogiers, O and Demuyser, L and Van Zeebroeck, G and Cen, Y and Kuchler, K and Brunke, S and Van Dijck, P}, title = {The involvement of the Candida glabrata trehalase enzymes in stress resistance and gut colonization.}, journal = {Virulence}, volume = {12}, number = {1}, pages = {329-345}, pmid = {33356857}, issn = {2150-5608}, support = {P 32582/FWF_/Austrian Science Fund FWF/Austria ; }, mesh = {Animals ; Candida glabrata/drug effects/*enzymology/*genetics/pathogenicity ; Female ; Fungal Proteins/*genetics/metabolism ; Gastrointestinal Tract/*microbiology ; Humans ; Hydrogen Peroxide/pharmacology ; Macrophages/microbiology ; Mice ; Mice, Inbred BALB C ; Oxidative Stress/genetics ; RAW 264.7 Cells ; Stress, Physiological/*genetics ; Trehalase/classification/*genetics/metabolism ; Virulence ; }, abstract = {Candida glabrata is an opportunistic human fungal pathogen and is frequently present in the human microbiome. It has a high relative resistance to environmental stresses and several antifungal drugs. An important component involved in microbial stress tolerance is trehalose. In this work, we characterized the three C. glabrata trehalase enzymes Ath1, Nth1 and Nth2. Single, double and triple deletion strains were constructed and characterized both in vitro and in vivo to determine the role of these enzymes in virulence. Ath1 was found to be located in the periplasm and was essential for growth on trehalose as sole carbon source, while Nth1 on the other hand was important for oxidative stress resistance, an observation which was consistent by the lower survival rate of the NTH1 deletion strain in human macrophages. No significant phenotype was observed for Nth2. The triple deletion strain was unable to establish a stable colonization of the gastrointestinal (GI) tract in mice indicating the importance of having trehalase activity for colonization in the gut.}, }
@article {pmid33354717, year = {2021}, author = {Stewart, AG and Satlin, MJ and Schlebusch, S and Isler, B and Forde, BM and Paterson, DL and Harris, PNA}, title = {Completing the Picture-Capturing the Resistome in Antibiotic Clinical Trials.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {72}, number = {12}, pages = {e1122-e1129}, doi = {10.1093/cid/ciaa1877}, pmid = {33354717}, issn = {1537-6591}, mesh = {Anti-Bacterial Agents/pharmacology/therapeutic use ; *Anti-Infective Agents/pharmacology ; Clinical Trials as Topic ; Drug Resistance, Microbial ; Humans ; *Microbiota/genetics ; }, abstract = {Despite the accepted dogma that antibiotic use is the largest contributor to antimicrobial resistance (AMR) and human microbiome disruption, our knowledge of specific antibiotic-microbiome effects remains basic. Detection of associations between new or old antimicrobials and specific AMR burden is patchy and heterogeneous. Various microbiome analysis tools are available to determine antibiotic effects on microbial communities in vivo. Microbiome analysis of treatment groups in antibiotic clinical trials, powered to measure clinically meaningful endpoints would greatly assist the antibiotic development pipeline and clinician antibiotic decision making.}, }
@article {pmid33352574, year = {2021}, author = {Martins, D and Mendes, F and Schmitt, F}, title = {Microbiome: A Supportive or a Leading Actor in Lung Cancer?.}, journal = {Pathobiology : journal of immunopathology, molecular and cellular biology}, volume = {88}, number = {2}, pages = {198-207}, doi = {10.1159/000511556}, pmid = {33352574}, issn = {1423-0291}, mesh = {Animals ; Carcinogenesis ; Dysbiosis/complications/*microbiology ; Humans ; Inflammation ; Lung/*microbiology/*pathology ; Lung Neoplasms/*microbiology ; Mice ; Microbiota/*immunology ; }, abstract = {Lung cancer is still the leading cause of cancer death worldwide. Despite the major diagnostic and therapeutic innovations, the effect on mortality has been modest and the overall survival is still poor. Better understanding of the pathology of these tumors is necessary in order to develop personalized therapeutic strategies in lung cancer patients. Human microbiome has been associated with normal physiology and function, and increasing evidence points towards a key role of the microbiome in promoting the progression of lung disease. Studies have shown that although poorly understood, lung has a distinctive microbiome that may an important role in lung cancer development and progression, and interactions between microbial populations have the potential to influence disease, suggesting that microbiome can be an emerging target in cancer therapeutics. We will review mechanisms how the lung microbiota influences carcinogenesis, focusing on the bacterial dysbiosis and inflammation. Moreover, we will discuss the link between the microbiome and cancer and the consequences induced by the immune system, as the host microbiota plays an essential role in activating and modulating the immune response. We summarize current research advances in the lung microbiome and demonstrate the potential to exploit microbiome as a mechanism to prevent carcinogenesis and modulate therapeutic strategy, suggesting microbiome as a valuable approach in lung cancer patients.}, }
@article {pmid33350604, year = {2021}, author = {Tranberg, A and Klarin, B and Johansson, J and Påhlman, LI}, title = {Efficacy of Lactiplantibacillus plantarum 299 and 299v against nosocomial oropharyngeal pathogens in vitro and as an oral prophylactic treatment in a randomized, controlled clinical trial.}, journal = {MicrobiologyOpen}, volume = {10}, number = {1}, pages = {e1151}, pmid = {33350604}, issn = {2045-8827}, mesh = {Adult ; Aged ; Aged, 80 and over ; Anti-Bacterial Agents/*therapeutic use ; Antibiosis/physiology ; Bacteria/*growth &amp; development ; Cross Infection/*therapy ; Female ; Humans ; Lactobacillus plantarum/*metabolism ; Male ; Microbiota/drug effects ; Middle Aged ; Oropharynx/microbiology ; Placebos/administration &amp; dosage ; Probiotics/*therapeutic use ; Respiratory Tract Infections/microbiology/*therapy ; Young Adult ; }, abstract = {BACKGROUND: Disturbance in the oropharyngeal microbiota is common in hospitalized patients and contributes to the development of nosocomial pneumonia. Lactiplantibacillus plantarum 299 and 299v (Lp299 and Lp299v) are probiotic bacteria with beneficial effects on the human microbiome.<br><br>AIM: To investigate how Lp299 and Lp299v affect the growth of nosocomial oropharyngeal pathogens in vitro and to evaluate the efficacy in vivo when these probiotics are administered prophylactically in hospitalized patients.<br><br>METHODS: The in vitro effect of Lp299 and Lp299v on nosocomial respiratory tract pathogens was evaluated using two methods, the co-culture and agar overlay. In the clinical study, patients were randomized to orally receive either probiotics or placebo twice daily during their hospital stay. Oropharyngeal swabs were analyzed at inclusion and every fourth day throughout hospitalization.<br><br>FINDINGS: All tested pathogens were completely inhibited by both Lp299 and Lp299v using the agar-overlay method. In the co-culture experiment, Lp299 and Lp299v significantly (p&#xa0;<&#xa0;0.05) reduced the growth of all pathogens except for Enterococcus faecalis co-incubated with Lp299. In the clinical study, daily oral treatment with Lp299 and Lp299v did not influence the development of disturbed oropharyngeal microbiota or nosocomial infection. Proton pump inhibitors, antibiotics, and steroid treatment were identified as risk factors for developing disturbed oropharyngeal microbiota.<br><br>CONCLUSIONS: Lp299 and Lp299v inhibited pathogen growth in vitro but did not affect the oropharyngeal microbiota in vivo. The ClinicalTrials.gov Identifier for this study is NCT02303301.}, }
@article {pmid33350360, year = {2021}, author = {Holster, S and Repsilber, D and Geng, D and Hyötyläinen, T and Salonen, A and Lindqvist, CM and Rajan, SK and de Vos, WM and Brummer, RJ and König, J}, title = {Correlations between microbiota and metabolites after faecal microbiota transfer in irritable bowel syndrome.}, journal = {Beneficial microbes}, volume = {12}, number = {1}, pages = {17-30}, doi = {10.3920/BM2020.0010}, pmid = {33350360}, issn = {1876-2891}, mesh = {Bacteria/classification/genetics/isolation &amp; purification/*metabolism ; *Fecal Microbiota Transplantation ; Feces/chemistry/microbiology ; Gastrointestinal Microbiome ; Humans ; Irritable Bowel Syndrome/*metabolism/microbiology/*therapy ; Phylogeny ; Treatment Outcome ; }, abstract = {Faecal microbiota transfer (FMT) consists of the infusion of donor faecal material into the intestine of a patient with the aim to restore a disturbed gut microbiota. In this study, it was investigated whether FMT has an effect on faecal microbial composition, its functional capacity, faecal metabolite profiles and their interactions in 16 irritable bowel syndrome (IBS) patients. Faecal samples from eight different time points before and until six months after allogenic FMT (faecal material from a healthy donor) as well as autologous FMT (own faecal material) were analysed by 16S RNA gene amplicon sequencing and gas chromatography coupled to mass spectrometry (GS-MS). The results showed that the allogenic FMT resulted in alterations in the microbial composition that were detectable up to six months, whereas after autologous FMT this was not the case. Similar results were found for the functional profiles, which were predicted from the phylogenetic sequencing data. While both allogenic FMT as well as autologous FMT did not have an effect on the faecal metabolites measured in this study, correlations between the microbial composition and the metabolites showed that the microbe-metabolite interactions seemed to be disrupted after allogenic FMT compared to autologous FMT. This shows that FMT can lead to altered interactions between the gut microbiota and its metabolites in IBS patients. Further research should investigate if and how this affects efficacy of FMT treatments.}, }
@article {pmid33343536, year = {2020}, author = {Yin, X and Altman, T and Rutherford, E and West, KA and Wu, Y and Choi, J and Beck, PL and Kaplan, GG and Dabbagh, K and DeSantis, TZ and Iwai, S}, title = {A Comparative Evaluation of Tools to Predict Metabolite Profiles From Microbiome Sequencing Data.}, journal = {Frontiers in microbiology}, volume = {11}, number = {}, pages = {595910}, pmid = {33343536}, issn = {1664-302X}, support = {R44 DA043954/DA/NIDA NIH HHS/United States ; }, abstract = {Metabolomic analyses of human gut microbiome samples can unveil the metabolic potential of host tissues and the numerous microorganisms they support, concurrently. As such, metabolomic information bears immense potential to improve disease diagnosis and therapeutic drug discovery. Unfortunately, as cohort sizes increase, comprehensive metabolomic profiling becomes costly and logistically difficult to perform at a large scale. To address these difficulties, we tested the feasibility of predicting the metabolites of a microbial community based solely on microbiome sequencing data. Paired microbiome sequencing (16S rRNA gene amplicons, shotgun metagenomics, and metatranscriptomics) and metabolome (mass spectrometry and nuclear magnetic resonance spectroscopy) datasets were collected from six independent studies spanning multiple diseases. We used these datasets to evaluate two reference-based gene-to-metabolite prediction pipelines and a machine-learning (ML) based metabolic profile prediction approach. With the pre-trained model on over 900 microbiome-metabolome paired samples, the ML approach yielded the most accurate predictions (i.e., highest F1 scores) of metabolite occurrences in the human gut and outperformed reference-based pipelines in predicting differential metabolites between case and control subjects. Our findings demonstrate the possibility of predicting metabolites from microbiome sequencing data, while highlighting certain limitations in detecting differential metabolites, and provide a framework to evaluate metabolite prediction pipelines, which will ultimately facilitate future investigations on microbial metabolites and human health.}, }
@article {pmid33343520, year = {2020}, author = {Aho, EL and Ogle, JM and Finck, AM}, title = {The Human Microbiome as a Focus of Antibiotic Discovery: Neisseria mucosa Displays Activity Against Neisseria gonorrhoeae.}, journal = {Frontiers in microbiology}, volume = {11}, number = {}, pages = {577762}, pmid = {33343520}, issn = {1664-302X}, support = {/WT_/Wellcome Trust/United Kingdom ; }, abstract = {Neisseria gonorrhoeae infections are a serious global health problem. This organism has developed disturbing levels of antibiotic resistance, resulting in the need for new approaches to prevent and treat gonorrhea. The genus Neisseria also includes several members of the human microbiome that live in close association with an array of microbial partners in a variety of niches. We designed an undergraduate antibiotic discovery project to examine a panel of nonpathogenic Neisseria species for their ability to produce antimicrobial secondary metabolites. Five strains belonging to the N. mucosa species group displayed activity against other Neisseria in delayed antagonism assays; three of these were active against N. gonorrhoeae. The antimicrobial compound secreted by N. mucosa NRL 9300 remained active in the presence of catalase, trypsin, and HEPES buffer, and effectively inhibited a DNA uptake mutant of N. gonorrhoeae. Antimicrobial activity was also retained in an ethyl acetate extract of plate grown N. mucosa NRL 9300. These data suggest N. mucosa produces an antimicrobial secondary metabolite that is distinct from previously described antigonococcal agents. This work also serves as a demonstration project that could easily be adapted to studying other members of the human microbiome in undergraduate settings. We offer the perspective that both introductory and more advanced course-based and apprentice-style antibiotic discovery projects focused on the microbiome have the potential to enrich undergraduate curricula and we describe transferrable techniques and strategies to facilitate project design.}, }
@article {pmid33339331, year = {2020}, author = {Łusiak-Szelachowska, M and Weber-Dąbrowska, B and Żaczek, M and Borysowski, J and Górski, A}, title = {The Presence of Bacteriophages in the Human Body: Good, Bad or Neutral?.}, journal = {Microorganisms}, volume = {8}, number = {12}, pages = {}, pmid = {33339331}, issn = {2076-2607}, support = {.//This work was supported by the statutory funds from the Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences./ ; }, abstract = {The presence of bacteriophages (phages) in the human body may impact bacterial microbiota and modulate immunity. The role of phages in human microbiome studies and diseases is poorly understood. However, the correlation between a greater abundance of phages in the gut in ulcerative colitis and diabetes has been suggested. Furthermore, most phages found at different sites in the human body are temperate, so their therapeutic effects and their potential beneficial effects remain unclear. Hence, far, no correlation has been observed between the presence of widespread crAssphage in the human population and human health and diseases. Here, we emphasize the beneficial effects of phage transfer in fecal microbiota transplantation (FMT) in Clostridioides difficile infection. The safety of phage use in gastrointestinal disorders has been demonstrated in clinical studies. The significance of phages in the FMT as well as in gastrointestinal disorders remains to be established. An explanation of the multifaceted role of endogenous phages for the development of phage therapy is required.}, }
@article {pmid33338541, year = {2021}, author = {Xu, CJ and Gruzieva, O and Qi, C and Esplugues, A and Gehring, U and Bergström, A and Mason, D and Chatzi, L and Porta, D and Lodrup Carlsen, KC and Baïz, N and Madore, AM and Alenius, H and van Rijkom, B and Jankipersadsing, SA and van der Vlies, P and Kull, I and van Hage, M and Bustamante, M and Lertxundi, A and Torrent, M and Santorelli, G and Fantini, MP and Hovland, V and Pesce, G and ,  and Fyhrquist, N and Laatikainen, T and Nawijn, MC and Li, Y and Wijmenga, C and Netea, MG and Bousquet, J and Anto, JM and Laprise, C and Haahtela, T and Annesi-Maesano, I and Carlsen, KH and Gori, D and Kogevinas, M and Wright, J and Söderhäll, C and Vonk, JM and Sunyer, J and Melén, E and Koppelman, GH}, title = {Shared DNA methylation signatures in childhood allergy: The MeDALL study.}, journal = {The Journal of allergy and clinical immunology}, volume = {147}, number = {3}, pages = {1031-1040}, pmid = {33338541}, issn = {1097-6825}, support = {P30 ES007048/ES/NIEHS NIH HHS/United States ; }, mesh = {Adolescent ; Asthma/*genetics ; Child ; Child, Preschool ; Cohort Studies ; CpG Islands/*genetics ; Cross-Sectional Studies ; DNA Methylation ; Eczema/*genetics ; Epigenesis, Genetic ; Female ; Humans ; Hypersensitivity/*genetics ; Immunoglobulin E/metabolism ; Male ; Rhinitis, Allergic/*genetics ; Transcriptome ; }, abstract = {BACKGROUND: Differential DNA methylation associated with allergy might provide novel insights into the shared or unique etiology of asthma, rhinitis, and eczema.<br><br>OBJECTIVE: We sought to identify DNA methylation&#xa0;profiles&#xa0;associated with childhood allergy.<br><br>METHODS: Within the European Mechanisms of the Development of Allergy (MeDALL) consortium, we performed an epigenome-wide association study of whole blood DNA methylation by using a cross-sectional design. Allergy was defined as having symptoms from at least 1 allergic disease (asthma, rhinitis, or eczema) and positive serum-specific IgE to common aeroallergens. The discovery study included 219 case patients and 417 controls at age 4 years and 228 case patients and 593 controls at age 8 years from 3 birth cohorts, with replication analyses in 325 case patients and 1111 controls. We performed additional analyses on 21 replicated sites in 785 case patients and 2124 controls by allergic symptoms only from 8 cohorts, 3 of which were not previously included in analyses.<br><br>RESULTS: We identified 80 differentially methylated CpG sites that showed a 1% to 3% methylation difference in the discovery phase, of which 21 (including 5 novel CpG sites) passed genome-wide significance after meta-analysis. All 21 CpG sites were also significantly differentially methylated with allergic symptoms and shared between asthma, rhinitis, and eczema. The 21 CpG sites mapped to relevant genes, including ACOT7, LMAN3, and CLDN23. All 21 CpG sties were differently methylated in asthma in isolated eosinophils, and 10 were replicated in respiratory epithelium.<br><br>CONCLUSION: Reduced whole blood DNA methylation at 21 CpG sites was significantly associated with childhood allergy. The findings provide novel insights into the shared molecular mechanisms underlying asthma, rhinitis, and eczema.}, }
@article {pmid33329475, year = {2020}, author = {Piñar, G and Sclocchi, MC and Pinzari, F and Colaizzi, P and Graf, A and Sebastiani, ML and Sterflinger, K}, title = {The Microbiome of Leonardo da Vinci's Drawings: A Bio-Archive of Their History.}, journal = {Frontiers in microbiology}, volume = {11}, number = {}, pages = {593401}, pmid = {33329475}, issn = {1664-302X}, abstract = {Seven emblematic Leonardo da Vinci's drawings were investigated through third generation sequencing technology (Nanopore). In addition, SEM analyses were carried out to acquire photographic documentation and to infer the nature of the micro-objects removed from the surface of the drawings. The Nanopore generated microbiomes can be used as a "bio-archive" of the drawings, offering a kind of fingerprint for current and future biological comparisons. This information might help to create a biological catalog of the drawings (cataloging), a microbiome-fingerprint for each single analyzed drawing, as a reference dataset for future studies (monitoring) and last but not least a bio-archive of the history of each single object (added value). Results showed a relatively high contamination with human DNA and a surprising dominance of bacteria over fungi. However, it was possible to identify typical bacteria of the human microbiome, which are mere contaminants introduced by handling of the drawings as well as other microorganisms that seem to have been introduced through vectors, such as insects and their droppings, visible through the SEM analyses. All drawings showed very specific bio-archives, but a core microbiome of bacteria and fungi that are repeatedly found in this type of material as true degraders were identified, such as members of the phyla Proteobacteria, Actinobacteria, and Firmicutes among bacteria, and fungi belonging to the classes Sordariomycetes and Eurotiomycetes. In addition, some similarities were observed that could be influenced by their geographical location (Rome or Turin), indicating the influence of this factor and denoting the importance of environmental and storage conditions on the specific microbiomes.}, }
@article {pmid33328144, year = {2021}, author = {Kolmeder, CA and de Vos, WM}, title = {Roadmap to functional characterization of the human intestinal microbiota in its interaction with the host.}, journal = {Journal of pharmaceutical and biomedical analysis}, volume = {194}, number = {}, pages = {113751}, doi = {10.1016/j.jpba.2020.113751}, pmid = {33328144}, issn = {1873-264X}, mesh = {*Gastrointestinal Microbiome/genetics ; Humans ; Metagenomics ; *Microbiota ; Phylogeny ; RNA, Ribosomal, 16S/genetics ; }, abstract = {It is known for more than 100 years that the intestinal microbes are important for the host's health and the last decade this is being intensely studied with a focus on the mechanistic aspects. Among the fundamental functions of the intestinal microbiome are the priming of the immune system, the production of essential vitamins and the energy harvest from foods. By now, several dozens of diseases, both intestinal and non-intestinal related, have been associated with the intestinal microbiome. Initially, this was based on the description of the composition between groups of different health status or treatment arms based on phylogenetic approaches based on the 16S rRNA gene sequences. This way of analysis has mostly moved to the analysis of all the genes or transcripts of the microbiome i.e. metagenomics and meta-transcriptomics. Differences are regularly found but these have to be taken with caution as we still do not know what the majority of genes of the intestinal microbiome are capable of doing. To circumvent this caveat researchers are studying the proteins and the metabolites of the microbiome and the host via metaproteomics and metabolomics approaches. However, also here the complexity is high and only a fraction of signals obtained with high throughput instruments can be identified and assigned to a known protein or molecule. Therefore, modern microbiome research needs advancement of existing and development of new analytical techniques. The usage of model systems like intestinal organoids where samples can be taken and processed rapidly as well as microfluidics systems may help. This review aims to elucidate what we know about the functionality of the human intestinal microbiome, what technologies are advancing this knowledge, and what innovations are still required to further evolve this actively developing field.}, }
@article {pmid33325062, year = {2021}, author = {Sidorina, A and Catesini, G and Levi Mortera, S and Marzano, V and Putignani, L and Boenzi, S and Taurisano, R and Garibaldi, M and Deodato, F and Dionisi-Vici, C}, title = {Combined proteomic and lipidomic studies in Pompe disease allow a better disease mechanism understanding.}, journal = {Journal of inherited metabolic disease}, volume = {44}, number = {3}, pages = {705-717}, doi = {10.1002/jimd.12344}, pmid = {33325062}, issn = {1573-2665}, mesh = {Adult ; Aryldialkylphosphatase/metabolism ; Autophagy/*physiology ; Child ; Child, Preschool ; Chromatography, Liquid ; Female ; Glycogen Storage Disease Type II/*metabolism ; Humans ; Infant ; Lactate Dehydrogenases/metabolism ; Lipid Metabolism ; Lipidomics/*methods ; Lysosomes/metabolism ; Male ; Phospholipids/metabolism ; Proteomics/*methods ; Tandem Mass Spectrometry ; }, abstract = {Pompe disease (PD) is caused by deficiency of the enzyme acid α-glucosidase resulting in glycogen accumulation in lysosomes. Clinical symptoms include skeletal myopathy, respiratory failure, and cardiac hypertrophy. We studied plasma proteomic and lipidomic profiles in 12 PD patients compared to age-matched controls. The proteomic profiles were analyzed by nLC-MS/MS SWATH method. Wide-targeted lipidomic analysis was performed by LC-IMS/MS, allowing to quantify >1100 lipid species, spanning 13 classes. Significant differences were found for 16 proteins, with four showing the most relevant changes (GPLD1, PON1, LDHB, PKM). Lipidomic analysis showed elevated levels of three phosphatidylcholines and of the free fatty acid 22:4, and reduced levels of six lysophosphatidylcholines. Up-regulated glycolytic enzymes (LDHB and PKM) are involved in autophagy and glycogen metabolism, while down-regulated PON1 and GPLD1 combined with lipidomic data indicate an abnormal phospholipid metabolism. Reduced GPLD1 and dysregulation of lipids with acyl-chains characteristic of GPI-anchor structure suggest the potential involvement of GPI-anchor system in PD. Results of proteomic analysis displayed the involvement of multiple cellular functions affecting inflammatory, immune and antioxidant responses, autophagy, Ca[2+] -homeostasis, and cell adhesion. The combined multi-omic approach revealed new biosignatures in PD, providing novel insights in disease pathophysiology with potential future clinical application.}, }
@article {pmid33324573, year = {2020}, author = {van Tilburg Bernardes, E and Gutierrez, MW and Arrieta, MC}, title = {The Fungal Microbiome and Asthma.}, journal = {Frontiers in cellular and infection microbiology}, volume = {10}, number = {}, pages = {583418}, pmid = {33324573}, issn = {2235-2988}, mesh = {Animals ; *Asthma ; Fungi ; Humans ; *Hypersensitivity ; Infant ; *Microbiota ; *Mycobiome ; }, abstract = {Asthma is a group of inflammatory conditions that compromises the airways of a continuously increasing number of people around the globe. Its complex etiology comprises both genetic and environmental aspects, with the intestinal and lung microbiomes emerging as newly implicated factors that can drive and aggravate asthma. Longitudinal infant cohort studies combined with mechanistic studies in animal models have identified microbial signatures causally associated with subsequent asthma risk. The recent inclusion of fungi in human microbiome surveys has revealed that microbiome signatures associated with asthma risk are not limited to bacteria, and that fungi are also implicated in asthma development in susceptible individuals. In this review, we examine the unique properties of human-associated and environmental fungi, which confer them the ability to influence immune development and allergic responses. The important contribution of fungi to asthma development and exacerbations prompts for their inclusion in current and future asthma studies in humans and animal models.}, }
@article {pmid33323705, year = {2020}, author = {Gomes, J&#xc1;P and Frizon, L and Demeda, VF}, title = {Ocular Surface Microbiome in Health and Disease.}, journal = {Asia-Pacific journal of ophthalmology (Philadelphia, Pa.)}, volume = {9}, number = {6}, pages = {505-511}, pmid = {33323705}, issn = {2162-0989}, mesh = {Bacteria/*isolation &amp; purification ; Eye/*microbiology ; Humans ; Microbiota/*genetics ; RNA, Ribosomal, 16S/*genetics/metabolism ; }, abstract = {The ocular surface is exposed continuously to the environment and, as a consequence, to a variety of different microbes. After the results of the Human Microbiome Project became publicly available, international research groups started to focus interest on exploring the ocular surface microbiome and its physiopathological relationship to the eye. For example, numerous research studies the existence of the ocular surface's bacterial flora, typically gathering cultures from healthy patients and finding few variations in the bacterial species. More recently, culture-independent methods, including 16S ribosomal ribonucleic acid (rRNA) gene sequencing, are being used to define the ocular microbiome. These newer methods suggest that the microbial communities have a greater diversity than previously reported. These communities seem to serve an immune-modulating function and maintain relationships with other microbes and organs, even distant ones. This review summarizes the literature exploring the ocular microbiome, both in health and in different diseases.}, }
@article {pmid33323129, year = {2020}, author = {Utter, DR and Borisy, GG and Eren, AM and Cavanaugh, CM and Mark Welch, JL}, title = {Metapangenomics of the oral microbiome provides insights into habitat adaptation and cultivar diversity.}, journal = {Genome biology}, volume = {21}, number = {1}, pages = {293}, pmid = {33323129}, issn = {1474-760X}, support = {P30 DK042086/DK/NIDDK NIH HHS/United States ; R01 DE022586/DE/NIDCR NIH HHS/United States ; UL1 TR001102/TR/NCATS NIH HHS/United States ; }, mesh = {Bacteria/*genetics ; Chromosome Mapping ; Haemophilus parainfluenzae/genetics ; Humans ; *Metagenome ; Microbiota/*genetics ; Micrococcaceae/genetics ; Mouth/*microbiology ; RNA, Ribosomal, 16S/genetics ; }, abstract = {BACKGROUND: The increasing availability of microbial genomes and environmental shotgun metagenomes provides unprecedented access to the genomic differences within related bacteria. The human oral microbiome with its diverse habitats and abundant, relatively well-characterized microbial inhabitants presents an opportunity to investigate bacterial population structures at an ecosystem scale.<br><br>RESULTS: Here, we employ a metapangenomic approach that combines public genomes with Human Microbiome Project (HMP) metagenomes to study the diversity of microbial residents of three oral habitats: tongue dorsum, buccal mucosa, and supragingival plaque. For two exemplar taxa, Haemophilus parainfluenzae and the genus Rothia, metapangenomes reveal distinct genomic groups based on shared genome content. H. parainfluenzae genomes separate into three distinct subgroups with differential abundance between oral habitats. Functional enrichment analyses identify an operon encoding oxaloacetate decarboxylase as diagnostic for the tongue-abundant subgroup. For the genus Rothia, grouping by shared genome content recapitulates species-level taxonomy and habitat preferences. However, while most R. mucilaginosa are restricted to the tongue as expected, two genomes represent a cryptic population of R. mucilaginosa in many buccal mucosa samples. For both H. parainfluenzae and the genus Rothia, we identify not only limitations in the ability of cultivated organisms to represent populations in their native environment, but also specifically which cultivar gene sequences are absent or ubiquitous.<br><br>CONCLUSIONS: Our findings provide insights into population structure and biogeography in the mouth and form specific hypotheses about habitat adaptation. These results illustrate the power of combining metagenomes and pangenomes to investigate the ecology and evolution of bacteria across analytical scales.}, }
@article {pmid33321195, year = {2021}, author = {Kantele, A and Lääveri, T and Kareinen, L and Pakkanen, SH and Blomgren, K and Mero, S and Patjas, A and Virtanen, J and Uusitalo, R and Lappalainen, M and Järvinen, A and Kurkela, S and Jääskeläinen, AJ and Vapalahti, O and Sironen, T}, title = {SARS-CoV-2 infections among healthcare workers at Helsinki University Hospital, Finland, spring 2020: Serosurvey, symptoms and risk factors.}, journal = {Travel medicine and infectious disease}, volume = {39}, number = {}, pages = {101949}, pmid = {33321195}, issn = {1873-0442}, mesh = {Adult ; Antibodies, Viral/blood ; Asymptomatic Infections/epidemiology ; COVID-19/diagnosis/*epidemiology/pathology/prevention &amp; control ; Female ; Finland/epidemiology ; Health Personnel/*statistics &amp; numerical data ; Hospitals, University ; Humans ; Male ; Middle Aged ; Risk Factors ; SARS-CoV-2/*immunology/isolation &amp; purification ; Seroepidemiologic Studies ; }, abstract = {BACKGROUND: Exposure, risks and immunity of healthcare workers (HCWs), a vital resource during the SARS-CoV-2 pandemic, warrant special attention.<br><br>METHODS: HCWs at Helsinki University Hospital, Finland, filled in questionnaires and provided serum samples for SARS-CoV-2-specific antibody screening by Euroimmun IgG assay in March-April 2020. Positive/equivocal findings were confirmed by Abbott and microneutralization tests. Positivity by two of the three assays or RT-PCR indicated a Covid-19 case (CoV+).<br><br>RESULTS: The rate of CoV(+) was 3.3% (36/1095) and seropositivity 3.0% (33/1095). CoV(+) was associated with contact with a known Covid-19 case, and working on a Covid-19-dedicated ward or one with cases among staff. The rate in the Covid-19-dedicated ICU was negligible. Smoking and age <55 years were associated with decreased risk. CoV(+) was strongly associated with ageusia, anosmia, myalgia, fatigue, fever, and chest pressure. Seropositivity was recorded for 89.3% of those with prior documented RT-PCR-positivity and 2.4% of those RT-PCR-negative. The rate of previously unidentified cases was 0.7% (8/1067) and asymptomatic ones 0% (0/36).<br><br>CONCLUSION: Undiagnosed and asymptomatic cases among HCWs proved rare. An increased risk was associated with Covid-19-dedicated wards. Particularly high rates were seen for wards with liberal HCW-HCW contacts, highlighting the importance of social distancing also among HCWs.}, }
@article {pmid33311550, year = {2020}, author = {Aluthge, ND and Tom, WA and Bartenslager, AC and Burkey, TE and Miller, PS and Heath, KD and Kreikemeier-Bower, C and Kittana, H and Schmaltz, RJ and Ramer-Tait, AE and Fernando, SC}, title = {Differential longitudinal establishment of human fecal bacterial communities in germ-free porcine and murine models.}, journal = {Communications biology}, volume = {3}, number = {1}, pages = {760}, pmid = {33311550}, issn = {2399-3642}, mesh = {Animals ; Bacteria/classification/genetics ; Biodiversity ; Computational Biology/methods ; Disease Models, Animal ; Feces/*microbiology ; *Gastrointestinal Microbiome ; Germ-Free Life ; Humans ; Metagenome ; Metagenomics/methods ; Mice ; Phylogeny ; Reproducibility of Results ; }, abstract = {The majority of microbiome studies focused on understanding mechanistic relationships between the host and the microbiota have used mice and other rodents as the model of choice. However, the domestic pig is a relevant model that is currently underutilized for human microbiome investigations. In this study, we performed a direct comparison of the engraftment of fecal bacterial communities from human donors between human microbiota-associated (HMA) piglet and mouse models under identical dietary conditions. Analysis of 16S rRNA genes using amplicon sequence variants (ASVs) revealed that with the exception of early microbiota from infants, the more mature microbiotas tested established better in the HMA piglets compared to HMA mice. Of interest was the greater transplantation success of members belonging to phylum Firmicutes in the HMA piglets compared to the HMA mice. Together, these results provide evidence for the HMA piglet model potentially being more broadly applicable for donors with more mature microbiotas while the HMA mouse model might be more relevant for developing microbiotas such as those of infants. This study also emphasizes the necessity to exercise caution in extrapolating findings from HMA animals to humans, since up to 28% of taxa from some donors failed to colonize either model.}, }
@article {pmid33307384, year = {2021}, author = {Ghemrawi, M and Torres, AR and Duncan, G and Colwell, R and Dadlani, M and McCord, B}, title = {The genital microbiome and its potential for detecting sexual assault.}, journal = {Forensic science international. Genetics}, volume = {51}, number = {}, pages = {102432}, doi = {10.1016/j.fsigen.2020.102432}, pmid = {33307384}, issn = {1878-0326}, mesh = {Adult ; Aged ; DNA, Bacterial/genetics ; Female ; High-Throughput Nucleotide Sequencing ; Humans ; Male ; Metagenomics ; *Microbiota ; Middle Aged ; Penis/*microbiology ; Pilot Projects ; Sequence Analysis, DNA ; *Sex Offenses ; Skin/microbiology ; Vagina/*microbiology ; Young Adult ; }, abstract = {Since its inception, the Human Microbiome Project (HMP) has provided key discoveries that can be applied to forensics, in addition to those of obvious medical value. Whether for postmortem interval estimation, geolocation, or human identification, there are many applications of the microbiome as an investigative lead for forensic casework. The human skin microbiome has shown great potential for use in studies of transfer and human identification, however there has been little focus on the genital microbiome, in particular penile skin which differs from other body sites. Our preliminary data on both the penile and vaginal microbiome demonstrates potential value in cases of sexual assault. In this study we describe genital microbial signatures based on the analysis of five male and five female genital samples and compare these results to those from longitudinal studies. Selected taxa, e.g., Gardnerella, Lactobacilli, Finegoldia, Peptoniphilus, and Anaerococci, are shown to be candidate constituents of the genital microbiome that merit investigation for use in sexual assault casework.}, }
@article {pmid33307241, year = {2021}, author = {Tsonis, O and Gkrozou, F and Paschopoulos, M}, title = {Microbiome affecting reproductive outcome in ARTs.}, journal = {Journal of gynecology obstetrics and human reproduction}, volume = {50}, number = {3}, pages = {102036}, doi = {10.1016/j.jogoh.2020.102036}, pmid = {33307241}, issn = {2468-7847}, mesh = {Bacteria/classification/isolation &amp; purification ; Endometrium/microbiology ; Fallopian Tubes/microbiology ; Female ; Genitalia/*microbiology ; Humans ; Infertility/*microbiology/therapy ; Male ; Microbiota/*physiology ; Ovary/microbiology ; Pregnancy ; Pregnancy Outcome ; *Reproductive Techniques, Assisted ; Semen/microbiology ; *Treatment Outcome ; Vagina/microbiology ; }, abstract = {Current scientific evidence reveals the importance of the human microbiome in health and disease. The presence of microbiota within the male and female reproductive tract has been well-documented and present theories imply that a possible disruption of their concentrations may have adverse effects on reproductive health and reproductive outcomes. Altered endometrial and vaginal microbiome could potential affect the reproductive outcome in infertile couples undergoing assisted reproductive techniques. Analysis of seminal fluids could also facilitate a prompt and appropriate approach in cases of abnormal male reproductive microflora. Essential knowledge on this subject could provide fertility experts better understanding with regards to unexplained fertility, increasing the success rates of ARTs. In this review, we summarise the current knowledge on the microbiota of the male and female reproductive tract and its impact on the success rates of ARTs in infertile couples.}, }
@article {pmid33305317, year = {2021}, author = {Creasy, HH and Felix, V and Aluvathingal, J and Crabtree, J and Ifeonu, O and Matsumura, J and McCracken, C and Nickel, L and Orvis, J and Schor, M and Giglio, M and Mahurkar, A and White, O}, title = {HMPDACC: a Human Microbiome Project Multi-omic data resource.}, journal = {Nucleic acids research}, volume = {49}, number = {D1}, pages = {D734-D742}, pmid = {33305317}, issn = {1362-4962}, support = {OT3 OD025459/OD/NIH HHS/United States ; U54 DK102556/DK/NIDDK NIH HHS/United States ; U54 HD080784/HD/NICHD NIH HHS/United States ; U54 DK102557/DK/NIDDK NIH HHS/United States ; U01 HG004866/HG/NHGRI NIH HHS/United States ; R24 DK110499/DK/NIDDK NIH HHS/United States ; }, mesh = {*Databases, Genetic ; Humans ; Internet ; *Microbiota ; Search Engine ; }, abstract = {The Human Microbiome Project (HMP) explored microbial communities of the human body in both healthy and disease states. Two phases of the HMP (HMP and iHMP) together generated >48TB of data (public and controlled access) from multiple, varied omics studies of both the microbiome and associated hosts. The Human Microbiome Project Data Coordination Center (HMPDACC) was established to provide a portal to access data and resources produced by the HMP. The HMPDACC provides a unified data repository, multi-faceted search functionality, analysis pipelines and standardized protocols to facilitate community use of HMP data. Recent efforts have been put toward making HMP data more findable, accessible, interoperable and reusable. HMPDACC resources are freely available at www.hmpdacc.org.}, }
@article {pmid33304855, year = {2020}, author = {Vural, M and Gilbert, B and Üstün, I and Caglar, S and Finckh, A}, title = {Mini-Review: Human Microbiome and Rheumatic Diseases.}, journal = {Frontiers in cellular and infection microbiology}, volume = {10}, number = {}, pages = {491160}, pmid = {33304855}, issn = {2235-2988}, mesh = {*Arthritis, Rheumatoid ; *Autoimmune Diseases ; Humans ; *Microbiota ; *Rheumatic Diseases/microbiology ; *Spondylarthritis ; }, abstract = {Rheumatoid arthritis and spondyloarthropathy are the most common inflammatory rheumatic diseases. As the human microbiome is involved in the immune homeostasis, it has the potential to be a key factor in the development of autoimmune diseases and rheumatic diseases. In this article, we review the role of various human microbiota on the pathogenesis of rheumatic diseases, focusing on spondylarthritis and rheumatoid arthritis.}, }
@article {pmid33304658, year = {2020}, author = {Koffert, J and Lahti, L and Nylund, L and Salminen, S and Hannukainen, JC and Salminen, P and de Vos, WM and Nuutila, P}, title = {Partial restoration of normal intestinal microbiota in morbidly obese women six months after bariatric surgery.}, journal = {PeerJ}, volume = {8}, number = {}, pages = {e10442}, pmid = {33304658}, issn = {2167-8359}, abstract = {We studied the impact of bariatric surgery on the intestinal microbiota of morbidly obese study subjects. A total of 13 morbidly obese women (five of which had type 2 diabetes) and 14 healthy age- and gender-matched controls were recruited and the microbiota composition of fecal samples were determined by using a phylogenetic microarray. Sampling of the patients took place just one month before and 6 months after the operation. Within six months after bariatric surgery, the obese subjects had lost on average a quarter of their weight whereas four of the five of the diabetic subjects were in remission. Bariatric surgery was associated with an increased microbial community richness and Bacteroidetes/Firmicutes ratio. In addition, we observed an increased relative abundance of facultative anaerobes, such as Streptococcus spp., and a reduction in specific butyrate-producing Firmicutes. The observed postoperative alterations in intestinal microbiota reflect adaptation to the changing conditions in the gastrointestinal tract, such as energy restriction and the inability to process fiber-rich foods after bariatric surgery.}, }
@article {pmid33301266, year = {2020}, author = {}, title = {Correction to "Do we have the guts to go? The abdominal compartment, intra-abdominal hypertension, the human microbiome and exploration class space missions".}, journal = {Canadian journal of surgery. Journal canadien de chirurgie}, volume = {63}, number = {6}, pages = {E609}, pmid = {33301266}, issn = {1488-2310}, }
@article {pmid33300552, year = {2021}, author = {Ventin-Holmberg, R and Eberl, A and Saqib, S and Korpela, K and Virtanen, S and Sipponen, T and Salonen, A and Saavalainen, P and Nissilä, E}, title = {Bacterial and Fungal Profiles as Markers of Infliximab Drug Response in Inflammatory Bowel Disease.}, journal = {Journal of Crohn's &amp; colitis}, volume = {15}, number = {6}, pages = {1019-1031}, doi = {10.1093/ecco-jcc/jjaa252}, pmid = {33300552}, issn = {1876-4479}, mesh = {Adult ; *Bacteria/classification/isolation &amp; purification ; Biomarkers, Pharmacological/analysis ; *Colitis, Ulcerative/drug therapy/microbiology ; Colonoscopy/methods ; *Crohn Disease/drug therapy/microbiology ; Drug Monitoring/methods/statistics &amp; numerical data ; Feces/*microbiology ; Female ; Finland/epidemiology ; *Fungi/classification/isolation &amp; purification ; Gastrointestinal Microbiome/*drug effects ; Humans ; Infliximab/*therapeutic use ; Male ; Tumor Necrosis Factor Inhibitors/therapeutic use ; }, abstract = {BACKGROUND AND AIMS: Inflammatory bowel diseases [IBDs], Crohn's disease [CD] and ulcerative colitis [UC], are globally increasing chronic gastro-intestinal inflammatory disorders associated with altered gut microbiota. Infliximab [IFX], a tumour necrosis factor [TNF]-alpha blocker, is used to treat IBD patients successfully, though one-third of the patients do not respond to therapy. No reliable biomarkers are available for prediction of IFX response. Our aims were to investigate the faecal bacterial and fungal communities during IFX therapy and find predictors for IFX treatment response in IBD patients.<br><br>METHODS: A total of 72 IBD patients [25 CD and 47 UC] started IFX therapy and were followed for 1 year or until IFX treatment was discontinued. An amplicon sequencing approach, targeting the bacterial 16S rRNA gene and fungal ITS 1 region separately, was used to determine the microbiota profiles in faecal samples collected before IFX therapy and 2, 6, and 12 weeks and 1 year after initiation of therapy. The response to IFX was evaluated by colonoscopy and clinically at 12 weeks after initiation.<br><br>RESULTS: Both faecal bacterial and fungal profiles differed significantly between response groups before start of IFX treatment. Non-responders had lower abundances of short chain fatty acid producers, particularly of the class Clostridia, and higher abundances of pro-inflammatory bacteria and fungi, such as the genus Candida, compared with responders. This was further indicated by bacterial taxa predicting the response in both CD and UC patients [area under the curve >0.8].<br><br>CONCLUSIONS: Faecal bacterial and fungal microbiota composition could provide a predictive tool to estimate IFX response in IBD patients.}, }
@article {pmid33299088, year = {2021}, author = {Malard, F and Dore, J and Gaugler, B and Mohty, M}, title = {Introduction to host microbiome symbiosis in health and disease.}, journal = {Mucosal immunology}, volume = {14}, number = {3}, pages = {547-554}, pmid = {33299088}, issn = {1935-3456}, mesh = {Animals ; Dysbiosis/*therapy ; Host Microbial Interactions ; Humans ; Iatrogenic Disease/*prevention &amp; control ; Metagenomics ; Microbiota/*physiology ; Nutrition Therapy ; Precision Medicine ; Symbiosis ; }, abstract = {Humans share a core intestinal microbiome and yet human microbiome differs by genes, species, enterotypes (ecology), and gene count (microbial diversity). Achievement of microbiota metagenomic analysis has revealed that the microbiome gene count is a key stratifier of health in several immune disorders and clinical conditions. We review here the progress of the metagenomic pipeline analysis, and how this has allowed us to define the host-microbe symbiosis associated with a healthy status. The link between host-microbe symbiosis disruption, the so-called dysbiosis and chronic diseases or iatrogenic conditions is highlighted. Finally, opportunities to use microbiota modulation, with specific nutrients and/or live microbes, as a target for personalized nutrition and therapy for the maintenance, preservation, or restoration of host-microbe symbiosis are discussed.}, }
@article {pmid33298912, year = {2020}, author = {Daisley, BA and Chanyi, RM and Abdur-Rashid, K and Al, KF and Gibbons, S and Chmiel, JA and Wilcox, H and Reid, G and Anderson, A and Dewar, M and Nair, SM and Chin, J and Burton, JP}, title = {Author Correction: Abiraterone acetate preferentially enriches for the gut commensal Akkermansia muciniphila in castrate-resistant prostate cancer patients.}, journal = {Nature communications}, volume = {11}, number = {1}, pages = {6394}, doi = {10.1038/s41467-020-20410-x}, pmid = {33298912}, issn = {2041-1723}, }
@article {pmid33297188, year = {2021}, author = {Harpaz, D and Veltman, B and Sadeh, Y and Marks, RS and Bernstein, N and Eltzov, E}, title = {The effect of cannabis toxicity on a model microbiome bacterium epitomized by a panel of bioluminescent E. coli.}, journal = {Chemosphere}, volume = {263}, number = {}, pages = {128241}, doi = {10.1016/j.chemosphere.2020.128241}, pmid = {33297188}, issn = {1879-1298}, mesh = {*Cannabis/toxicity ; Dronabinol/toxicity ; Escherichia coli/genetics ; Humans ; *Microbiota ; Plant Extracts ; }, abstract = {The world acceptance of medical cannabis slowly widens. Cannabinoids are known as the main therapeutic active compounds in the cannabis plant, yet their bioactive physiological effects are still unknown. In this study, the mode of action of nine selected cannabinoids was examined using a bioluminescent bacterial panel, as well as the extracts of six different cannabis varieties and cannabinoids standards artificial mixtures. The bacterial panel was composed of genetically modified E. coli bacteria that is commonly found in the gut microbiome, to which a lux operon was added to various stress promoters. The panel was exposed to the cannabinoids in order to identify bacterial defense mechanism, via the aforementioned specific stress types response. This enables the understanding of the toxicity mode of action of cannabinoids. From all the tested cannabinoids, only delta-9-tetrahydrocannabinol (THC) and delta-9-tetrahydrocannabinolic acid A (THCA) produced a genotoxic effect, while the other tested cannabinoids, demonstrated cytotoxic or oxidative damages. Unlike pure cannabinoids, cannabis plant extracts exhibited mostly genotoxicity, with minor cytotoxicity or oxidative stress responses. Moreover, cannabinoids standards artificial mixtures produced a different response patterns compared to their individual effects, which may be due to additional synergistic or antagonistic reactions between the mixed chemicals on the bacterial panel. The results showed that despite the lack of cannabigerol (CBG), cannabidivarin (CBDV), cannabinol (CBN), and cannabichromene (CBC) in the artificial solution mimicking the CN6 cannabis variety, a similar response pattern to the cannabinoids standards mixture was obtained. This work contributes to the understanding of such correlations and may provide a realistic view of cannabinoid effects on the human microbiome.}, }
@article {pmid33291949, year = {2021}, author = {Chen, CX and Carpenter, JS and Murphy, T and Brooks, P and Fortenberry, JD}, title = {Engaging Adolescent and Young Adults in Microbiome Sample Self-Collection: Strategies for Success.}, journal = {Biological research for nursing}, volume = {23}, number = {3}, pages = {402-407}, pmid = {33291949}, issn = {1552-4175}, support = {KL2 TR002530/TR/NCATS NIH HHS/United States ; UL1 TR002529/TR/NCATS NIH HHS/United States ; }, mesh = {Adolescent ; Female ; *Gastrointestinal Microbiome ; Humans ; *Microbiota ; Prospective Studies ; RNA, Ribosomal, 16S ; Specimen Handling ; Young Adult ; }, abstract = {Human microbiome research provides rich opportunities to elucidate factors influencing health, uncover novel biomarkers, and expand disease treatment options. A well-conducted microbiome study depends not only on a rigorous design but also on successfully engaging participants in collecting quality samples. In this paper, we aim to describe (1) strategies our team used to engage adolescents and young adults in vaginal and gut microbiome sample self-collection and (2) their effectiveness. In our prospective, longitudinal, feasibility study of 20 female adolescents and young adults, research participants self-collected vaginal and gut microbiome samples at home. Using a participatory and iterative process, we developed strategies to engage participants in sample self-collection, including (1) providing clear instructions to ensure comprehension and buy-in, (2) providing a user-friendly take-home package, (3) minimizing disgust/embarrassment associated with sample collection, and (4) follow-up communications to facilitate sample collections and return. With these strategies, we achieved 100% participant retention and 100% sample return rates. All samples (n = 80, 100%) were usable for downstream 16s rRNA gene sequencing and analysis. All participants rated the study procedures as acceptable, and qualitative data showed that strategies were well received by participants. This study suggests that carefully planning and implementing strategies to engage participants in sample self-collection can result in high degrees of participant compliance, sample quality, and participant satisfaction in microbiome research.}, }
@article {pmid33290720, year = {2021}, author = {Durrant, MG and Bhatt, AS}, title = {Automated Prediction and Annotation of Small Open Reading Frames in Microbial Genomes.}, journal = {Cell host &amp; microbe}, volume = {29}, number = {1}, pages = {121-131.e4}, pmid = {33290720}, issn = {1934-6069}, support = {P30 CA124435/CA/NCI NIH HHS/United States ; R01 AI143757/AI/NIAID NIH HHS/United States ; R01 AI148623/AI/NIAID NIH HHS/United States ; }, mesh = {Bacteria/*genetics ; Bacterial Proteins/genetics ; Computational Biology ; Deep Learning ; *Genome, Bacterial ; Humans ; Markov Chains ; Microbiota ; Models, Theoretical ; *Molecular Sequence Annotation ; *Open Reading Frames ; }, abstract = {Small open reading frames (smORFs) and their encoded microproteins play central roles in microbes. However, there is a vast unexplored space of smORFs within human-associated microbes. A recent bioinformatic analysis used evolutionary conservation signals to enhance prediction of small protein families. To facilitate the annotation of specific smORFs, we introduce SmORFinder. This tool combines profile hidden Markov models of each smORF family and deep learning models that better generalize to smORF families not seen in the training set, resulting in predictions enriched for Ribo-seq translation signals. Feature importance analysis reveals that the deep learning models learn to identify Shine-Dalgarno sequences, deprioritize the wobble position in each codon, and group codon synonyms found in the codon table. A core-genome analysis of 26 bacterial species identifies several core smORFs of unknown function. We pre-compute smORF annotations for thousands of RefSeq isolate genomes and Human Microbiome Project metagenomes and provide these data through a public web portal.}, }
@article {pmid33283070, year = {2020}, author = {Banerjee, S and Suter, MA and Aagaard, KM}, title = {Interactions between Environmental Exposures and the Microbiome: Implications for Fetal Programming.}, journal = {Current opinion in endocrine and metabolic research}, volume = {13}, number = {}, pages = {39-48}, pmid = {33283070}, issn = {2451-9650}, support = {R00 HD075858/HD/NICHD NIH HHS/United States ; R01 HD091731/HD/NICHD NIH HHS/United States ; P42 ES027725/ES/NIEHS NIH HHS/United States ; R21 ES029462/ES/NIEHS NIH HHS/United States ; P30 DK020593/DK/NIDDK NIH HHS/United States ; R01 DK089201/DK/NIDDK NIH HHS/United States ; K99 HD075858/HD/NICHD NIH HHS/United States ; R24 DK090964/DK/NIDDK NIH HHS/United States ; P50 MD015496/MD/NIMHD NIH HHS/United States ; }, abstract = {Decades of population-based health outcomes data highlight the importance of understanding how environmental exposures in pregnancy affect maternal and neonatal outcomes. Animal model research and epidemiological studies have revealed that such exposures are able to alter fetal programming through stable changes in the epigenome, including altered DNA methylation patterns and histone modifications in the developing fetus and infant. It is similarly known that while microbes can biotransform environmental chemicals via conjugation and de-conjugation, specific exposures can also alter the community profile and function of the human microbiome. In this review, we consider how alterations to the maternal and or fetal/infant microbiome through environmental exposures could directly and indirectly alter fetal programming. We highlight two specific environmental exposures, cadmium (Cd) and polycyclic aromatic hydrocarbons (PAHs), and outline their effects on the developing fetus and the perinatal (maternal and fetal/infant) microbiome. We further consider how chemical exposures in the setting of natural disasters may be of particular importance to environmental health.}, }
@article {pmid33281770, year = {2020}, author = {Hiippala, K and Barreto, G and Burrello, C and Diaz-Basabe, A and Suutarinen, M and Kainulainen, V and Bowers, JR and Lemmer, D and Engelthaler, DM and Eklund, KK and Facciotti, F and Satokari, R}, title = {Novel Odoribacter splanchnicus Strain and Its Outer Membrane Vesicles Exert Immunoregulatory Effects in vitro.}, journal = {Frontiers in microbiology}, volume = {11}, number = {}, pages = {575455}, pmid = {33281770}, issn = {1664-302X}, abstract = {Odoribacter splanchnicus, belonging to the order Bacteroidales, is a common, short-chain fatty acid producing member of the human intestinal microbiota. A decreased abundance of Odoribacter has been linked to different microbiota-associated diseases, such as non-alcoholic fatty liver disease, cystic fibrosis and inflammatory bowel disease (IBD). The type strain of O. splanchnicus has been genome-sequenced, but otherwise very little is known about this anaerobic bacterium. The species surfaces in many microbiota studies and, consequently, comprehension on its interactions with the host is needed. In this study, we isolated a novel strain of O. splanchnicus from a healthy fecal donor, identified it by genome sequencing and addressed its adhesive, epithelium reinforcing and immunoregulatory properties. Our results show that O. splanchnicus strain 57 is non-adherent to enterocytes or mucus, does not reinforce nor compromise Caco-2 monolayer integrity and most likely harbors penta-acylated, less endotoxic lipid A as part of its lipopolysaccharide (LPS) structure based on the lack of gene lpxM and in vitro results on low-level NF-κB activity. The studies by transmission electron microscopy revealed that O. splanchnicus produces outer membrane vesicles (OMV). O. splanchnicus cells, culture supernatant i.e., spent medium or OMVs did not induce interleukin-8 (IL-8) response in HT-29 enterocyte cells suggesting a very low proinflammatory capacity. On the contrary, the treatment of HT-29 cells with O. splanchnicus cells, spent medium or OMVs prior to exposure to Escherichia coli LPS elicited a significant decrease in IL-8 production as compared to E. coli LPS treatment alone. Moreover, O. splanchnicus spent supernatant induced IL-10 production by immune cells, suggesting anti-inflammatory activity. Our in vitro findings indicate that O. splanchnicus and its effector molecules transported in OMVs could potentially exert anti-inflammatory action in the gut epithelium. Taken together, O. splanchnicus seems to be a commensal with a primarily beneficial interaction with the host.}, }
@article {pmid33278908, year = {2020}, author = {Kirkpatrick, AW and Hamilton, DR and McKee, JL and MacDonald, B and Pelosi, P and Ball, CG and Roberts, D and McBeth, PB and Cocolini, F and Ansaloni, L and Peireira, B and Sugrue, M and Campbell, MR and Kimball, EJ and Malbrain, MLNG and Roberts, D}, title = {Do we have the guts to go? The abdominal compartment, intra-abdominal hypertension, the human microbiome and exploration class space missions.}, journal = {Canadian journal of surgery. Journal canadien de chirurgie}, volume = {63}, number = {6}, pages = {E581-E593}, pmid = {33278908}, issn = {1488-2310}, mesh = {Abdomen/physiopathology ; Animals ; Critical Illness ; Dysbiosis/etiology/*physiopathology/prevention &amp; control ; Gastrointestinal Microbiome/physiology ; Humans ; Intra-Abdominal Hypertension/etiology/*physiopathology/prevention &amp; control ; Models, Animal ; Multiple Organ Failure/etiology/*physiopathology/prevention &amp; control ; *Space Flight ; Weightlessness/*adverse effects ; }, abstract = {Humans are destined to explore space, yet critical illness and injury may be catastrophically limiting for extraterrestrial travel. Humans are superorganisms living in symbiosis with their microbiomes, whose genetic diversity dwarfs that of humans. Symbiosis is critical and imbalances are associated with disease, occurring within hours of serious illness and injury. There are many characteristics of space flight that negatively influence the microbiome, especially deep space itself, with its increased radiation and absence of gravity. Prolonged weightlessness causes many physiologic changes that are detrimental; some resemble aging and will adversely affect the ability to tolerate critical illness or injury and subsequent treatment. Critical illness-induced intra-abdominal hypertension (IAH) may induce malperfusion of both the viscera and microbiome, with potentially catastrophic effects. Evidence from animal models confirms profound IAH effects on the gut, namely ischemia and disruption of barrier function, mechanistically linking IAH to resultant organ dysfunction. Therefore, a pathologic dysbiome, space-induced immune dysfunction and a diminished cardiorespiratory reserve with exacerbated susceptibility to IAH, imply that a space-deconditioned astronaut will be vulnerable to IAH-induced gut malperfusion. This sets the stage for severe gut ischemia and massive biomediator generation in an astronaut with reduced cardiorespiratory/immunological capacity. Fortunately, experiments in weightless analogue environments suggest that IAH may be ameliorated by conformational abdominal wall changes and a resetting of thoracoabdominal mechanics. Thus, review of the interactions of physiologic changes with prolonged weightlessness and IAH is required to identify appropriate questions for planning exploration class space surgical care.}, }
@article {pmid33277504, year = {2020}, author = {Tian, L and Wang, XW and Wu, AK and Fan, Y and Friedman, J and Dahlin, A and Waldor, MK and Weinstock, GM and Weiss, ST and Liu, YY}, title = {Deciphering functional redundancy in the human microbiome.}, journal = {Nature communications}, volume = {11}, number = {1}, pages = {6217}, pmid = {33277504}, issn = {2041-1723}, support = {K01 HL130629/HL/NHLBI NIH HHS/United States ; R01 AI042347/AI/NIAID NIH HHS/United States ; U19 AI095219/AI/NIAID NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; U01 HL089856/HL/NHLBI NIH HHS/United States ; R01 AI141529/AI/NIAID NIH HHS/United States ; R01 HD093761/HD/NICHD NIH HHS/United States ; UH3 OD023268/OD/NIH HHS/United States ; }, mesh = {Algorithms ; Bacteria/classification/genetics ; Feces/*microbiology ; Gastrointestinal Microbiome/*genetics ; Gastrointestinal Tract/*microbiology ; Gene Regulatory Networks ; Gene Transfer, Horizontal ; Humans ; Metagenome/*genetics ; Metagenomics/*methods ; Microbiota/*genetics ; Models, Genetic ; }, abstract = {Although the taxonomic composition of the human microbiome varies tremendously across individuals, its gene composition or functional capacity is highly conserved - implying an ecological property known as functional redundancy. Such functional redundancy has been hypothesized to underlie the stability and resilience of the human microbiome, but this hypothesis has never been quantitatively tested. The origin of functional redundancy is still elusive. Here, we investigate the basis for functional redundancy in the human microbiome by analyzing its genomic content network - a bipartite graph that links microbes to the genes in their genomes. We find that this network exhibits several topological features that favor high functional redundancy. Furthermore, we develop a simple genome evolution model to generate genomic content network, finding that moderate selection pressure and high horizontal gene transfer rate are necessary to generate genomic content networks with key topological features that favor high functional redundancy. Finally, we analyze data from two published studies of fecal microbiota transplantation (FMT), finding that high functional redundancy of the recipient's pre-FMT microbiota raises barriers to donor microbiota engraftment. This work elucidates the potential ecological and evolutionary processes that create and maintain functional redundancy in the human microbiome and contribute to its resilience.}, }
@article {pmid33274243, year = {2020}, author = {Kasperkiewicz, K and Świerzko, AS and Przybyła, M and Szemraj, J and Barski, J and Skurnik, M and Kałużyński, A and Cedzyński, M}, title = {The Role of Yersinia enterocolitica O:3 Lipopolysaccharide in Collagen-Induced Arthritis.}, journal = {Journal of immunology research}, volume = {2020}, number = {}, pages = {7439506}, pmid = {33274243}, issn = {2314-7156}, mesh = {Animals ; Arthritis, Experimental ; Arthritis, Rheumatoid/*etiology/metabolism/pathology ; Autoimmunity ; Biomarkers ; Collagen/adverse effects/immunology ; Complement Pathway, Mannose-Binding Lectin/immunology ; Disease Susceptibility ; Lipopolysaccharides/*pharmacology ; Male ; Mannose-Binding Lectin/metabolism ; Mice ; Phenotype ; Protein Binding ; RNA, Messenger/genetics ; Yersinia Infections/*complications/*immunology/microbiology ; Yersinia enterocolitica/*immunology ; }, abstract = {Yersinia enterocolitica O:3 is mentioned among the most common arthritogenic pathogens. Bacterial components (including lipopolysaccharide (LPS)) may persist in the joint after eradication of infection. Having an adjuvant activity, LPS may enhance production of anticollagen antibodies, involved in the pathogenesis of rheumatoid arthritis. Furthermore, its ability to activate complement contributes to the inflammation. The aim of this work was to investigate whether Yersinia LPS (coinjected with collagen) is associated with arthritis progression or other pathological effects and to elucidate the mechanism of this association. It was demonstrated that murine mannose-binding lectin C (MBL-C) recognizes the inner core heptoses of the Rd1 chemotype LPS of Yersinia. In addition, the Rd1 LPS activates the MBL-associated serine protease 1 (MASP-1) stronger than the S and Ra chemotype LPS and comparable to Klebsiella pneumoniae O:3 LPS. However, in contrast to the latter, Yersinia Rd1 LPS was associated neither with the adjuvancity nor with the enhancement of pathological changes in animal paws/impairment of motility. On the other hand, it seemed to be more hepatotoxic when compared with the other tested endotoxins, while the enlargement of inguinal lymph nodes and drop in hepatic MBL-C expression (at the mRNA level) were independent of LPS chemotype. Our data did not suggest no greater impact Y. enterocolitica O:3 on the development or severity of arthropathy related to anticollagen antibody-induced arthritis in mice, although its interaction with MBL-C and subsequent complement activation may contribute to some adverse effects.}, }
@article {pmid33272203, year = {2020}, author = {Zhang, Q and Dao, T}, title = {A distance based multisample test for high-dimensional compositional data with applications to the human microbiome.}, journal = {BMC bioinformatics}, volume = {21}, number = {Suppl 9}, pages = {205}, pmid = {33272203}, issn = {1471-2105}, mesh = {Aged ; Bayes Theorem ; Computer Simulation ; Humans ; Metagenomics ; *Microbiota ; Middle Aged ; Numerical Analysis, Computer-Assisted ; }, abstract = {BACKGROUND: Compositional data refer to the data that lie on a simplex, which are common in many scientific domains such as genomics, geology and economics. As the components in a composition must sum to one, traditional tests based on unconstrained data become inappropriate, and new statistical methods are needed to analyze this special type of data.<br><br>RESULTS: In this paper, we consider a general problem of testing for the compositional difference between K populations. Motivated by microbiome and metagenomics studies, where the data are often over-dispersed and high-dimensional, we formulate a well-posed hypothesis from a Bayesian point of view and suggest a nonparametric test based on inter-point distance to evaluate statistical significance. Unlike most existing tests for compositional data, our method does not rely on any data transformation, sparsity assumption or regularity conditions on the covariance matrix, but directly analyzes the compositions. Simulated data and two real data sets on the human microbiome are used to illustrate the promise of our method.<br><br>CONCLUSIONS: Our simulation studies and real data applications demonstrate that the proposed test is more sensitive to the compositional difference than the mean-based method, especially when the data are over-dispersed or zero-inflated. The proposed test is easy to implement and computationally efficient, facilitating its application to large-scale datasets.}, }
@article {pmid33269394, year = {2020}, author = {Marco, ML and Hill, C and Hutkins, R and Slavin, J and Tancredi, DJ and Merenstein, D and Sanders, ME}, title = {Should There Be a Recommended Daily Intake of Microbes?.}, journal = {The Journal of nutrition}, volume = {150}, number = {12}, pages = {3061-3067}, pmid = {33269394}, issn = {1541-6100}, mesh = {*Diet ; *Dietary Supplements ; *Food Microbiology ; Humans ; *Microbiota ; Nutrition Policy ; Nutritional Requirements ; Prebiotics ; Probiotics ; *Recommended Dietary Allowances ; }, abstract = {The collective findings from human microbiome research, randomized controlled trials on specific microbes (i.e., probiotics), and associative studies of fermented dairy consumption provide evidence for the beneficial effects of the regular consumption of safe live microbes. To test the hypothesis that the inclusion of safe, live microbes in the diet supports and improves health, we propose assessment of the types and evidentiary quality of the data available on microbe intake, including the assembly and evaluation of evidence available from dietary databases. Such an analysis would help to identify gaps in the evidence needed to test this hypothesis, which can then be used to formulate and direct initiatives focused on prospective and randomized controlled trials on live microbe consumption. Outcomes will establish whether or not the evidence exists, or can be generated, to support the establishment of dietary recommendations for live microbes.}, }
@article {pmid33268781, year = {2020}, author = {Lin, H and Peddada, SD}, title = {Analysis of microbial compositions: a review of normalization and differential abundance analysis.}, journal = {NPJ biofilms and microbiomes}, volume = {6}, number = {1}, pages = {60}, pmid = {33268781}, issn = {2055-5008}, mesh = {Bacteria/*classification ; *Gastrointestinal Microbiome ; Humans ; Models, Theoretical ; Mouth/*microbiology ; Phylogeny ; }, abstract = {Increasingly, researchers are discovering associations between microbiome and a wide range of human diseases such as obesity, inflammatory bowel diseases, HIV, and so on. The first step towards microbiome wide association studies is the characterization of the composition of human microbiome under different conditions. Determination of differentially abundant microbes between two or more environments, known as differential abundance (DA) analysis, is a challenging and an important problem that has received considerable interest during the past decade. It is well documented in the literature that the observed microbiome data (OTU/SV table) are relative abundances with an excess of zeros. Since relative abundances sum to a constant, these data are necessarily compositional. In this article we review some recent methods for DA analysis and describe their strengths and weaknesses.}, }
@article {pmid33264344, year = {2020}, author = {Park, IH and Lee, JS and Park, JH and Kang, SH and Hong, SM and Park, IS and Yoon, JH and Hong, SJ}, title = {Comparison of the human microbiome in adults and children with chronic rhinosinusitis.}, journal = {PloS one}, volume = {15}, number = {12}, pages = {e0242770}, pmid = {33264344}, issn = {1932-6203}, mesh = {Adult ; Bacteria/metabolism ; Biodiversity ; Child ; Chronic Disease ; Female ; Humans ; Male ; *Microbiota ; Rhinitis/*microbiology ; Sinusitis/*microbiology ; }, abstract = {We hypothesized that differences in the microbiome could be a cause of the substantial differences in the symptoms of and treatment options for adult and pediatric patients with chronic rhinosinusitis (CRS). First, we characterized the differences in the nasal microbiomes of pediatric and adult CRS patients. Swabs were obtained from 19 patients with chronic rhinosinusitis (9 children and 10 adults). The bacterial 16S rRNA gene was pyrosequenced to compare the microbiota of the middle meatus. No significant differences were found in species richness and alpha-diversity indices between the two groups. However, in the comparison of diversity between groups using the unweighted pair group method with arithmetic mean (UPGMA) clustering of microbiome taxonomic profiles, we observed a relatively clear separation between the adult and pediatric groups. Actinobacteria had a significantly higher relative abundance in the adult group than in the pediatric group at the phylum level. At the genus level, Corynebacterium showed significantly higher relative abundance in the adult group than in the pediatric group. This is a comparative study between the microbiomes of adult and pediatric CRS patients. We expect this study to be the first step in understanding the pathogenesis of CRS in adults and children using microbiome analysis.}, }
@article {pmid33264062, year = {2021}, author = {Lamousé-Smith, E and Kelly, D and De Cremoux, I}, title = {Designing bugs as drugs: exploiting the gut microbiome.}, journal = {American journal of physiology. Gastrointestinal and liver physiology}, volume = {320}, number = {3}, pages = {G295-G303}, pmid = {33264062}, issn = {1522-1547}, mesh = {Animals ; Anti-Bacterial Agents/pharmacology ; Bacteria/drug effects/metabolism ; Biological Therapy/methods ; Drug Design/methods ; Gastrointestinal Agents/pharmacology ; *Gastrointestinal Microbiome ; Humans ; }, abstract = {The extensive investigation of the human microbiome and the accumulating evidence regarding its critical relationship to human health and disease has advanced recognition of its potential as the next frontier of drug development. The rapid development of technologies, directed at understanding the compositional and functional dynamics of the human microbiome, and the ability to mine for novel therapeutic targets and biomarkers are leading innovative efforts to develop microbe-derived drugs that can prevent and treat autoimmune, metabolic, and infectious diseases. Increasingly, academics, biotechs, investors, and large pharmaceutical companies are partnering to collectively advance various therapeutic modalities ranging from live bacteria to small molecules. We review the leading platforms in current development focusing on live microbial consortia, engineered microbes, and microbial-derived metabolites. We will also touch on how the field is addressing and challenging the traditional definitions of pharmacokinetics and pharmacodynamics, dosing, toxicity, and safety to advance the development of these novel and cutting-edge therapeutics into the clinic.}, }
@article {pmid33263886, year = {2020}, author = {Federici, S and Suez, J and Elinav, E}, title = {Our Microbiome: On the Challenges, Promises, and Hype.}, journal = {Results and problems in cell differentiation}, volume = {69}, number = {}, pages = {539-557}, pmid = {33263886}, issn = {0080-1844}, mesh = {Fecal Microbiota Transplantation ; Humans ; *Microbiota ; Prebiotics ; Probiotics ; }, abstract = {The microbiome field is increasingly raising interest among scientists, clinicians, biopharmaceutical entities, and the general public. Technological advances from the past two decades have enabled the rapid expansion of our ability to characterize the human microbiome in depth, highlighting its previously underappreciated role in contributing to multifactorial diseases including those with unknown etiology. Consequently, there is growing evidence that the microbiome could be utilized in medical diagnosis and patient stratification. Moreover, multiple gut microbes and their metabolic products may be bioactive, thereby serving as future potential microbiome-targeting or -associated therapeutics. Such therapies could include new generation probiotics, prebiotics, fecal microbiota transplantations, postbiotics, and dietary modulators. However, microbiome research has also been associated with significant limitations, technical and conceptual challenges, and, at times, "over-hyped" expectations that microbiome research will produce quick solutions to chronic and mechanistically complex human disorders. Herein, we summarize these challenges and also discuss some of the realistic promises associated with microbiome research and its applicability into clinical application.}, }
@article {pmid33262241, year = {2020}, author = {, }, title = {Coordinating and Assisting Research at the SARS-CoV-2/Microbiome Nexus.}, journal = {mSystems}, volume = {5}, number = {6}, pages = {}, pmid = {33262241}, issn = {2379-5077}, support = {K01 HL141589/HL/NHLBI NIH HHS/United States ; }, abstract = {Although the COVID-19 pandemic is caused by a single virus, the rest of the human microbiome appears to be involved in the disease and could influence vaccine responses while offering opportunities for microbiome-directed therapeutics. The newly formed Microbiome Centers Consortium (MCC) surveyed its membership and identified four ways to leverage the strengths and experience of microbiome centers in the response to the COVID-19 pandemic. To meet these needs, the MCC will provide a platform to coordinate clinical and environmental research, assist with practical obstacles, and help communicate the connections between the microbiome and COVID-19. We ask that microbiome researchers join us in these efforts to address the ongoing pandemic.}, }
@article {pmid33258596, year = {2020}, author = {Gray, HK and Arora-Williams, KK and Young, C and Bouwer, E and Davis, MF and Preheim, SP}, title = {Contribution of Time, Taxonomy, and Selective Antimicrobials to Antibiotic and Multidrug Resistance in Wastewater Bacteria.}, journal = {Environmental science &amp; technology}, volume = {54}, number = {24}, pages = {15946-15957}, pmid = {33258596}, issn = {1520-5851}, support = {K01 OD019918/OD/NIH HHS/United States ; }, mesh = {Anti-Bacterial Agents/pharmacology ; *Anti-Infective Agents/pharmacology ; Bacteria ; Drug Resistance, Bacterial ; Drug Resistance, Multiple ; Humans ; Microbial Sensitivity Tests ; *Wastewater ; }, abstract = {The use of nontherapeutic broad-spectrum antimicrobial agents triclosan (TCS) and benzalkonium chloride (BC) can contribute to bacterial resistance to clinically relevant antibiotics. Antimicrobial-resistant bacteria within wastewater may reflect the resistance burden within the human microbiome, as antibiotics and pathogens in wastewater can track with clinically relevant parameters during perturbations to the community. In this study, we monitored culturable and resistant wastewater bacteria and cross-resistance to clinically relevant antibiotics to gauge the impact of each antimicrobial and identify factors influencing cross-resistance profiles. Bacteria resistant to TCS and BC were isolated from wastewater influent over 21 months, and cross-resistance, taxonomy, and monthly changes were characterized under both antimicrobial selection regimes. Cross-resistance profiles from each antimicrobial differed within and between taxa. BC-isolated bacteria had a significantly higher prevalence of resistance to "last-resort antibiotic" colistin, while isolates resistant to TCS exhibited higher rates of multidrug resistance. Prevalence of culturable TCS-resistant bacteria decreased over time following Food and Drug Administration (FDA) TCS bans. Cross-resistance patterns varied according to sampling date, including among the most clinically important antibiotics. Correlations between strain-specific resistance profiles were largely influenced by taxonomy, with some variations associated with sampling date. The results reveal that time, taxonomy, and selection by TCS and BC impact features of cross-resistance patterns among diverse wastewater microorganisms, which could reflect the variety of factors influencing resistance patterns relevant to a community microbiome.}, }
@article {pmid33255779, year = {2020}, author = {Ricci, V and Carcione, D and Messina, S and Colombo, GI and D'Alessandra, Y}, title = {Circulating 16S RNA in Biofluids: Extracellular Vesicles as Mirrors of Human Microbiome?.}, journal = {International journal of molecular sciences}, volume = {21}, number = {23}, pages = {}, pmid = {33255779}, issn = {1422-0067}, support = {5&#x2030; 2015//Ministero della Salute/ ; }, mesh = {Bacteria/classification/genetics ; Cell-Free Nucleic Acids/*genetics ; Dysbiosis/*genetics/microbiology/pathology ; Extracellular Vesicles/*genetics ; Feces/microbiology ; High-Throughput Nucleotide Sequencing ; Humans ; Microbiota/genetics ; RNA, Ribosomal, 16S/*genetics ; }, abstract = {The human body is inhabited by around 10[13] microbes composing a multicomplex system, termed microbiota, which is strongly involved in the regulation and maintenance of homeostasis. Perturbations in microbiota composition can lead to dysbiosis, which has been associated with several human pathologies. The gold-standard method to explore microbial composition is next-generation sequencing, which involves the analysis of 16S rRNA, an indicator of the presence of specific microorganisms and the principal tool used in bacterial taxonomic classification. Indeed, the development of 16S RNA sequencing allows us to explore microbial composition in several environments and human body districts and fluids, since it has been detected in "germ-free" environments such as blood, plasma, and urine of diseased and healthy subjects. Recently, prokaryotes showed to generate extracellular vesicles, which are known to be responsible for shuttling different intracellular components such as proteins and nucleic acids (including 16S molecules) by protecting their cargo from degradation. These vesicles can be found in several human biofluids and can be exploited as tools for bacterial detection and identification. In this review, we examine the complex link between circulating 16S RNA molecules and bacteria-derived vesicles.}, }
@article {pmid33254225, year = {2021}, author = {Pacifici, R}, title = {Role of Gut Microbiota in the Skeletal Response to PTH.}, journal = {The Journal of clinical endocrinology and metabolism}, volume = {106}, number = {3}, pages = {636-645}, pmid = {33254225}, issn = {1945-7197}, support = {S10 RR028009/RR/NCRR NIH HHS/United States ; R01 DK124821/DK/NIDDK NIH HHS/United States ; R01 AR054625/AR/NIAMS NIH HHS/United States ; R01 DK112946/DK/NIDDK NIH HHS/United States ; R01 DK119229/DK/NIDDK NIH HHS/United States ; R01 DK108842/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Bone Development/drug effects ; Bone Marrow/drug effects/physiology ; Bone Marrow Cells/drug effects/physiology ; Bone Remodeling/drug effects ; Bone and Bones/*drug effects/physiology ; Gastrointestinal Microbiome/*physiology ; Humans ; Parathyroid Hormone/*pharmacology ; }, abstract = {Exposed surfaces of mammals are colonized with 100 trillion indigenous bacteria, fungi, and viruses, creating a diverse ecosystem known as the human microbiome. The gut microbiome is the richest microbiome and is now known to regulate postnatal skeletal development and the activity of the major endocrine regulators of bone. Parathyroid hormone (PTH) is one of the bone-regulating hormone that requires elements of the gut microbiome to exert both its bone catabolic and its bone anabolic effects. How the gut microbiome regulates the skeletal response to PTH is object of intense research. Involved mechanisms include absorption and diffusion of bacterial metabolites, such as short-chain fatty acids, and trafficking of immune cells from the gut to the bone marrow. This review will focus on how the gut microbiome communicates and regulates bone marrow cells in order to modulate the skeletal effects of PTH.}, }
@article {pmid33253350, year = {2021}, author = {Hassan, R and Allali, I and Agamah, FE and Elsheikh, SSM and Thomford, NE and Dandara, C and Chimusa, ER}, title = {Drug response in association with pharmacogenomics and pharmacomicrobiomics: towards a better personalized medicine.}, journal = {Briefings in bioinformatics}, volume = {22}, number = {4}, pages = {}, doi = {10.1093/bib/bbaa292}, pmid = {33253350}, issn = {1477-4054}, mesh = {*Drug Therapy ; *Gastrointestinal Microbiome ; *Genome-Wide Association Study ; Humans ; *Pharmaceutical Preparations ; *Pharmacogenetics ; *Precision Medicine ; }, abstract = {Researchers have long been presented with the challenge imposed by the role of genetic heterogeneity in drug response. For many years, Pharmacogenomics and pharmacomicrobiomics has been investigating the influence of an individual's genetic background to drug response and disposition. More recently, the human gut microbiome has proven to play a crucial role in the way patients respond to different therapeutic drugs and it has been shown that by understanding the composition of the human microbiome, we can improve the drug efficacy and effectively identify drug targets. However, our knowledge on the effect of host genetics on specific gut microbes related to variation in drug metabolizing enzymes, the drug remains limited and therefore limits the application of joint host-microbiome genome-wide association studies. In this paper, we provide a historical overview of the complex interactions between the host, human microbiome and drugs. While discussing applications, challenges and opportunities of these studies, we draw attention to the critical need for inclusion of diverse populations and the development of an innovative and combined pharmacogenomics and pharmacomicrobiomics approach, that may provide an important basis in personalized medicine.}, }
@article {pmid33245146, year = {2021}, author = {Hernandez, CJ}, title = {Musculoskeletal microbiology: The utility of the microbiome in orthopedics.}, journal = {Journal of orthopaedic research : official publication of the Orthopaedic Research Society}, volume = {39}, number = {2}, pages = {251-257}, pmid = {33245146}, issn = {1554-527X}, support = {R56 AG067997/AG/NIA NIH HHS/United States ; R21 AR073454/AR/NIAMS NIH HHS/United States ; R01 AG067997/AG/NIA NIH HHS/United States ; R21AR068061/AR/NIAMS NIH HHS/United States ; R21AR073454/AR/NIAMS NIH HHS/United States ; R21AR0671534/AR/NIAMS NIH HHS/United States ; R21 AR068061/AR/NIAMS NIH HHS/United States ; R21 AR071534/AR/NIAMS NIH HHS/United States ; R56AG067997/AG/NIA NIH HHS/United States ; }, mesh = {Animals ; Bone and Bones/physiology ; Chronic Disease ; *Gastrointestinal Microbiome ; Humans ; Musculoskeletal Diseases/epidemiology/*microbiology ; Orthopedics ; Prevalence ; Prosthesis-Related Infections/prevention &amp; control ; }, abstract = {The past 15 years have witnessed a renaissance in the study of the microbes that colonize the human body. The vast majority of the human microbiome resides within the gut. Alterations to the gut microbiome have been associated with the pathogenesis and progression of wide-ranging diseases throughout the body-including atherosclerosis, depression, and obesity. Our understanding of the effects of the gut microbiome on the musculoskeletal system remains in its infancy, but preclinical work has demonstrated an effect of the gut microbiome on the success of orthopedic surgical procedures, osteoporosis, osteoarthritis, and muscle mass. In this perspective I review preclinical findings demonstrating that an impaired presurgical gut microbiome can increase the likelihood of developing periprosthetic joint infection and how alterations in the gut microbiome can reduce bone strength by impairing bone tissue material properties. In addition to discussing these examples, I review the hypothesis that many chronic non-communicable diseases have become more prevalent in modern industrialized societies as a result of changes in the composition of the gut microbiome resulting from changes in environment/lifestyle (diet, sanitation, antibiotic use). The most burdensome musculoskeletal disorders are chronic and non-communicable and may therefore be related to generational shifts in the composition of the gut microbiome, a possibility I illustrate by reviewing changes in the prevalence of osteoarthritis over the last century. Microbiome-based therapeutics are potentially innocuous, inexpensive, and have the potential to be effective with only occasional use, making them attractive for addressing the needs of chronic and/or slowly progressing musculoskeletal disorders.}, }
@article {pmid33245088, year = {2021}, author = {Prihoda, D and Maritz, JM and Klempir, O and Dzamba, D and Woelk, CH and Hazuda, DJ and Bitton, DA and Hannigan, GD}, title = {The application potential of machine learning and genomics for understanding natural product diversity, chemistry, and therapeutic translatability.}, journal = {Natural product reports}, volume = {38}, number = {6}, pages = {1100-1108}, doi = {10.1039/d0np00055h}, pmid = {33245088}, issn = {1460-4752}, mesh = {*Biological Products/chemistry/pharmacology ; Biosynthetic Pathways/genetics ; Drug Discovery ; *Genomics ; Humans ; *Machine Learning ; Microbiota ; }, abstract = {Covering: up to the end of 2020. The machine learning field can be defined as the study and application of algorithms that perform classification and prediction tasks through pattern recognition instead of explicitly defined rules. Among other areas, machine learning has excelled in natural language processing. As such methods have excelled at understanding written languages (e.g. English), they are also being applied to biological problems to better understand the "genomic language". In this review we focus on recent advances in applying machine learning to natural products and genomics, and how those advances are improving our understanding of natural product biology, chemistry, and drug discovery. We discuss machine learning applications in genome mining (identifying biosynthetic signatures in genomic data), predictions of what structures will be created from those genomic signatures, and the types of activity we might expect from those molecules. We further explore the application of these approaches to data derived from complex microbiomes, with a focus on the human microbiome. We also review challenges in leveraging machine learning approaches in the field, and how the availability of other "omics" data layers provides value. Finally, we provide insights into the challenges associated with interpreting machine learning models and the underlying biology and promises of applying machine learning to natural product drug discovery. We believe that the application of machine learning methods to natural product research is poised to accelerate the identification of new molecular entities that may be used to treat a variety of disease indications.}, }
@article {pmid33236419, year = {2020}, author = {Montecchiani, V and Fanos, V}, title = {Human microbiome and allergy.}, journal = {Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology}, volume = {31 Suppl 26}, number = {}, pages = {5-7}, doi = {10.1111/pai.13360}, pmid = {33236419}, issn = {1399-3038}, mesh = {*Asthma ; *Gastrointestinal Microbiome ; Humans ; *Hypersensitivity ; *Microbiota ; Respiratory System ; }, abstract = {Human microbiome contributes to critical functions that impact health and disease. It influences the development of the immune system, and the pathogenesis of immunological disorders included allergy. While it is easy to understand how airway microbiome, influencing local inflammation and immune activity, could contribute to shaping asthma phenotype, it is not so obvious to understand the influence by the gut microbiome, but there is growing evidence about it. The increase of allergic disorders in western countries led to investigate the role environment is playing and how it may change our microbiome and immune system, with the hope of finding new preventive approaches for allergy.}, }
@article {pmid33236315, year = {2021}, author = {Hasan, A and Hasan, LK and Schnabl, B and Greytak, M and Yadlapati, R}, title = {Microbiome of the Aerodigestive Tract in Health and Esophageal Disease.}, journal = {Digestive diseases and sciences}, volume = {66}, number = {1}, pages = {12-18}, pmid = {33236315}, issn = {1573-2568}, support = {P30 DK120515/DK/NIDDK NIH HHS/United States ; 120515/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Esophageal Diseases/diagnosis/*microbiology/physiopathology ; Esophagus/microbiology/physiology ; *Gastrointestinal Microbiome/physiology ; Gastrointestinal Tract/*microbiology/physiology ; Humans ; Lung/*microbiology/physiology ; }, abstract = {The diverse human gut microbiome is comprised of approximately 40 trillion microorganisms representing up to 1000 different bacterial species. The human microbiome plays a critical role in gut epithelial health and disease susceptibility. While the interaction between gut microbiome and gastrointestinal pathology is increasingly understood, less is known about the interaction between the microbiome and the aerodigestive tract. This review of the microbiome of the aerodigestive tract in health, and alterations in microbiome across esophageal pathologies highlights important findings and areas for future research. First, microbiome profiles are distinct along the aerodigestive tract, spanning the oral cavity to the stomach. In patients with reflux-related disease such as gastro-esophageal reflux disease, Barrett's esophagus, and esophageal adenocarcinoma, investigators have observed an overall increase in gram negative bacteria in the esophageal microbiome compared to healthy individuals. However, whether differences in microbiome promote disease development, or if these shifts are a consequence of disease remains unknown. Interestingly, use of proton pump inhibitor therapy is also associated with shifts in the microbiome, with distinct shifts and patterns along the aerodigestive tract. The relationship between the human gut microbiome and esophageal pathology is a ripe area for investigation, and further understanding of these pathways may promote development of novel targets in prevention and therapy for esophageal diseases.}, }
@article {pmid33232449, year = {2020}, author = {Lyles, JK and Oli, M}, title = {The student-centered classroom: the new gut feeling.}, journal = {FEMS microbiology letters}, volume = {367}, number = {22}, pages = {}, pmid = {33232449}, issn = {1574-6968}, mesh = {Adolescent ; Adult ; Female ; Fermentation ; Humans ; Male ; Microbiology/*education ; Microbiota ; Probiotics ; Research/*education ; Surveys and Questionnaires ; Teaching/*standards/statistics &amp; numerical data ; *Universities ; Young Adult ; }, abstract = {A student-centered, interactive course-based undergraduate research experience (CURE) was implemented in a microbiology course in order to provide an authentic research experience and to stimulate student interest and improve understanding of fermentation, probiotics, the human microbiome and related topics. Students were immersed in the scientific process as they used fundamental techniques to investigate the probiotic composition of a fermented milk beverage, kefir-an unknown question with no predetermined outcomes. In order to assess the benefits and effect of this learning experience on the students, pre- and post-study surveys were administered using Qualtrics. Post-study, 93% of participants agreed that fermented foods are beneficial to human health (compared to 52% pre-study), and notably, 100% of participants indicated that they plan to apply this material in both their personal and professional lives and would suggest consuming probiotics or fermented products to alleviate gastrointestinal issues. As evidenced by demographic data, this CURE is suitable for implementation at both large and small institutions with diverse student populations. Collectively, these data indicate that this collaborative, discovery-based learning experience is a powerful educational tool, encouraging students to make real-life connections between microbiology, medicine and their own health.}, }
@article {pmid33227982, year = {2020}, author = {Vernocchi, P and Gili, T and Conte, F and Del Chierico, F and Conta, G and Miccheli, A and Botticelli, A and Paci, P and Caldarelli, G and Nuti, M and Marchetti, P and Putignani, L}, title = {Network Analysis of Gut Microbiome and Metabolome to Discover Microbiota-Linked Biomarkers in Patients Affected by Non-Small Cell Lung Cancer.}, journal = {International journal of molecular sciences}, volume = {21}, number = {22}, pages = {}, pmid = {33227982}, issn = {1422-0067}, mesh = {Akkermansia/classification/genetics/isolation &amp; purification ; Alcohols/metabolism ; Aldehydes/metabolism ; Antineoplastic Agents, Immunological/therapeutic use ; Bacteroides/classification/genetics/isolation &amp; purification ; Carcinoma, Non-Small-Cell Lung/drug therapy/*genetics/immunology/microbiology ; Clostridiaceae/classification/genetics/isolation &amp; purification ; Databases, Genetic ; Disease Progression ; Drug Monitoring/methods ; Fatty Acids, Volatile/metabolism ; Gastrointestinal Microbiome/genetics/*immunology ; *Gene Expression Regulation, Neoplastic ; *Gene Regulatory Networks ; Humans ; Immunotherapy/methods ; Indoles/metabolism ; Lung Neoplasms/drug therapy/*genetics/immunology/microbiology ; Metabolome/genetics/*immunology ; Metagenomics/methods ; Peptostreptococcus/classification/genetics/isolation &amp; purification ; Precision Medicine/methods ; Programmed Cell Death 1 Receptor/antagonists &amp; inhibitors/genetics/immunology ; RNA, Ribosomal, 16S/genetics ; Signal Transduction ; }, abstract = {Several studies in recent times have linked gut microbiome (GM) diversity to the pathogenesis of cancer and its role in disease progression through immune response, inflammation and metabolism modulation. This study focused on the use of network analysis and weighted gene co-expression network analysis (WGCNA) to identify the biological interaction between the gut ecosystem and its metabolites that could impact the immunotherapy response in non-small cell lung cancer (NSCLC) patients undergoing second-line treatment with anti-PD1. Metabolomic data were merged with operational taxonomic units (OTUs) from 16S RNA-targeted metagenomics and classified by chemometric models. The traits considered for the analyses were: (i) condition: disease or control (CTRLs), and (ii) treatment: responder (R) or non-responder (NR). Network analysis indicated that indole and its derivatives, aldehydes and alcohols could play a signaling role in GM functionality. WGCNA generated, instead, strong correlations between short-chain fatty acids (SCFAs) and a healthy GM. Furthermore, commensal bacteria such as Akkermansia muciniphila, Rikenellaceae, Bacteroides, Peptostreptococcaceae, Mogibacteriaceae and Clostridiaceae were found to be more abundant in CTRLs than in NSCLC patients. Our preliminary study demonstrates that the discovery of microbiota-linked biomarkers could provide an indication on the road towards personalized management of NSCLC patients.}, }
@article {pmid33227623, year = {2021}, author = {Araujo, DV and Watson, GA and Oliva, M and Heirali, A and Coburn, B and Spreafico, A and Siu, LL}, title = {Bugs as drugs: The role of microbiome in cancer focusing on immunotherapeutics.}, journal = {Cancer treatment reviews}, volume = {92}, number = {}, pages = {102125}, doi = {10.1016/j.ctrv.2020.102125}, pmid = {33227623}, issn = {1532-1967}, mesh = {Animals ; Gastrointestinal Microbiome/*physiology ; Humans ; Immunotherapy/*methods ; Mice ; Microbiota/*physiology ; Neoplasms/*drug therapy ; Prebiotics/*standards ; Probiotics/pharmacology/*therapeutic use ; }, abstract = {The human microbiome comprising microorganisms, their collective genomes and metabolic products has gained tremendous research interest in oncology, as multiple cohorts and case studies have demonstrated discernible interpatient differences in this ecosystem based on clinical variables including disease type, stage, diet, antibiotic usage, cancer treatments, therapeutic responses and toxicities. The modulation of the gut microbiome is the subject of many ongoing preclinical and clinical investigations, through the manipulation of diet, as well as the use of prebiotics, probiotics, specific antibiotics, fecal microbial transplantation, microbial consortia and stool substitutes. Standardization and quality control are needed to maximize the information being generated in this growing field, ranging from technical assays to measure microbiome composition, to methodological aspects in the analysis and reporting of results. Proof-of-mechanism and proof-of-concept clinical trials with appropriate controls are needed to confirm or refute the feasibility, safety and ultimately the clinical utility of human microbiome modulation in cancer patients.}, }
@article {pmid33227575, year = {2021}, author = {McKenzie, ND and Hong, H and Ahmad, S and Holloway, RW}, title = {The gut microbiome and cancer immunotherapeutics: A review of emerging data and implications for future gynecologic cancer research.}, journal = {Critical reviews in oncology/hematology}, volume = {157}, number = {}, pages = {103165}, doi = {10.1016/j.critrevonc.2020.103165}, pmid = {33227575}, issn = {1879-0461}, mesh = {Female ; *Gastrointestinal Microbiome ; *Genital Neoplasms, Female/therapy ; Humans ; Immunity ; Immunotherapy ; *Microbiota ; Tumor Microenvironment ; }, abstract = {Investigation of the gynecologic tract microbial milieu has revealed potential new biomarkers. Simultaneously, immunotherapeutics are establishing their place in the treatment of gynecologic malignancies. The interplay between the microbiome, the tumor micro-environment and response to therapy is a burgeoning area of interest. There is evidence to support that microbes, through their genetic make-up, gene products, and metabolites affect human physiology, metabolism, immunity, disease susceptibility, response to pharmacotherapy, and the severity of disease-related side effects. Specifically, the richness and diversity of the gut microbiome appears to affect carcinogenesis, response to immunotherapy, and modulate severity of immune-mediated adverse effects. These effects have best been described in other tumor types and these have shown compelling results. This review summarizes the current understanding and scope of the interplay between the human microbiome, host factors, cancer, and response to treatments. These findings support further exploring whether these associations exist for gynecologic malignancies.}, }
@article {pmid33226693, year = {2021}, author = {Teles, F and Wang, Y and Hajishengallis, G and Hasturk, H and Marchesan, JT}, title = {Impact of systemic factors in shaping the periodontal microbiome.}, journal = {Periodontology 2000}, volume = {85}, number = {1}, pages = {126-160}, doi = {10.1111/prd.12356}, pmid = {33226693}, issn = {1600-0757}, support = {R01 DE024767/DE/NIDCR NIH HHS/United States ; }, mesh = {*Arthritis, Rheumatoid ; Female ; Humans ; Metagenomics ; *Microbiota ; Pregnancy ; RNA, Ribosomal, 16S/genetics ; }, abstract = {Since 2010, next-generation sequencing platforms have laid the foundation to an exciting phase of discovery in oral microbiology as it relates to oral and systemic health and disease. Next-generation sequencing has allowed large-scale oral microbial surveys, based on informative marker genes, such as 16S ribosomal RNA, community gene inventories (metagenomics), and functional analyses (metatranscriptomics), to be undertaken. More specifically, the availability of next-generation sequencing has also paved the way for studying, in greater depth and breadth, the effect of systemic factors on the periodontal microbiome. It was natural to investigate systemic diseases, such as diabetes, in such studies, along with systemic conditions or states, , pregnancy, menopause, stress, rheumatoid arthritis, and systemic lupus erythematosus. In addition, in recent years, the relevance of systemic "variables" (ie, factors that are not necessarily diseases or conditions, but may modulate the periodontal microbiome) has been explored in detail. These include ethnicity and genetics. In the present manuscript, we describe and elaborate on the new and confirmatory findings unveiled by next-generation sequencing as it pertains to systemic factors that may shape the periodontal microbiome. We also explore the systemic and mechanistic basis for such modulation and highlight the importance of those relationships in the management and treatment of patients.}, }
@article {pmid33226688, year = {2021}, author = {Duran-Pinedo, AE}, title = {Metatranscriptomic analyses of the oral microbiome.}, journal = {Periodontology 2000}, volume = {85}, number = {1}, pages = {28-45}, doi = {10.1111/prd.12350}, pmid = {33226688}, issn = {1600-0757}, support = {/DE/NIDCR NIH HHS/United States ; 2R01DE021553/NH/NIH HHS/United States ; }, mesh = {Biofilms ; *Dental Caries ; Humans ; *Microbiota/genetics ; Mouth ; *Periodontal Diseases ; }, abstract = {Although the composition of the oral human microbiome is now well studied, regulation of genes within oral microbial communities remains mostly uncharacterized. Current concepts of periodontal disease and caries highlight the importance of oral biofilms and their role as etiological agents of those diseases. Currently, there is increased interest in exploring and characterizing changes in the composition and gene-expression profiles of oral microbial communities. These efforts aim to identify changes in functional activities that could explain the transition from health to disease and the reason for the chronicity of those infections. It is now clear that the functions of distinct species within the subgingival microbiota are intimately intertwined with the rest of the microbial community. This point highlights the relevance of examining the expression profile of specific species within the subgingival microbiota in the case of periodontal disease or caries lesions, in the context of the other members of the biofilm in vivo. Metatranscriptomic analysis of the oral community is the starting point for identifying environmental signals that modulate the shift in metabolism of the community from commensal to dysbiotic. These studies give a snapshot of the expression patterns of microbial communities and also allow us to determine triggers to diseases. For example, in the case of caries, studies have unveiled a potential new pathway of sugar metabolism, namely the use of sorbitol as an additional source of carbon by Streptococcus mutans; and in the case of periodontal disease, high levels of extracellular potassium could be a signal of disease. Longitudinal studies are needed to identify the real markers of the initial stages of caries and periodontal disease. More information on the gene-expression profiles of the host, along with the patterns from the microbiome, will lead to a clearer understanding of the modulation of health and disease. This review presents a summary of these initial studies, which have opened the door to a new understanding of the dynamics of the oral community during the dysbiotic process in the oral cavity.}, }
@article {pmid33221926, year = {2021}, author = {Kasmanas, JC and Bartholomäus, A and Corrêa, FB and Tal, T and Jehmlich, N and Herberth, G and von Bergen, M and Stadler, PF and Carvalho, ACPLF and Nunes da Rocha, U}, title = {HumanMetagenomeDB: a public repository of curated and standardized metadata for human metagenomes.}, journal = {Nucleic acids research}, volume = {49}, number = {D1}, pages = {D743-D750}, pmid = {33221926}, issn = {1362-4962}, mesh = {*Data Curation ; Databases, Genetic/*standards ; Humans ; Metadata/*standards ; *Metagenome ; Metagenomics ; Reference Standards ; User-Computer Interface ; }, abstract = {Metagenomics became a standard strategy to comprehend the functional potential of microbial communities, including the human microbiome. Currently, the number of metagenomes in public repositories is increasing exponentially. The Sequence Read Archive (SRA) and the MG-RAST are the two main repositories for metagenomic data. These databases allow scientists to reanalyze samples and explore new hypotheses. However, mining samples from them can be a limiting factor, since the metadata available in these repositories is often misannotated, misleading, and decentralized, creating an overly complex environment for sample reanalysis. The main goal of the HumanMetagenomeDB is to simplify the identification and use of public human metagenomes of interest. HumanMetagenomeDB version 1.0 contains metadata of 69 822 metagenomes. We standardized 203 attributes, based on standardized ontologies, describing host characteristics (e.g. sex, age and body mass index), diagnosis information (e.g. cancer, Crohn's disease and Parkinson), location (e.g. country, longitude and latitude), sampling site (e.g. gut, lung and skin) and sequencing attributes (e.g. sequencing platform, average length and sequence quality). Further, HumanMetagenomeDB version 1.0 metagenomes encompass 58 countries, 9 main sample sites (i.e. body parts), 58 diagnoses and multiple ages, ranging from just born to 91 years old. The HumanMetagenomeDB is publicly available at https://webapp.ufz.de/hmgdb/.}, }
@article {pmid33217332, year = {2021}, author = {Münch, PC and Franzosa, EA and Stecher, B and McHardy, AC and Huttenhower, C}, title = {Identification of Natural CRISPR Systems and Targets in the Human Microbiome.}, journal = {Cell host &amp; microbe}, volume = {29}, number = {1}, pages = {94-106.e4}, pmid = {33217332}, issn = {1934-6069}, support = {P30 DK043351/DK/NIDDK NIH HHS/United States ; R24 DK110499/DK/NIDDK NIH HHS/United States ; U54 DK102557/DK/NIDDK NIH HHS/United States ; }, mesh = {Bacteria/*genetics/metabolism ; Bacteriophages/genetics/physiology ; CRISPR-Associated Proteins/genetics ; *CRISPR-Cas Systems ; *Clustered Regularly Interspaced Short Palindromic Repeats ; Gastrointestinal Microbiome/genetics ; Gene Ontology ; Genes, Bacterial ; Genome, Bacterial ; Humans ; Metagenome ; Methylation ; Microbiota/*genetics ; Mouth/microbiology ; Viral Proteins/genetics/metabolism ; Virus Physiological Phenomena ; }, abstract = {Many bacteria resist invasive DNA by incorporating sequences into CRISPR loci, which enable sequence-specific degradation. CRISPR systems have been well studied from isolate genomes, but culture-independent metagenomics provide a new window into their diversity. We profiled CRISPR loci and cas genes in the body-wide human microbiome using 2,355 metagenomes, yielding functional and taxonomic profiles for 2.9 million spacers by aligning the spacer content to each sample's metagenome and corresponding gene families. Spacer and repeat profiles agree qualitatively with those from isolate genomes but expand their diversity by approximately 13-fold, with the highest spacer load present in the oral microbiome. The taxonomy of spacer sequences parallels that of their source community, with functional targets enriched for viral elements. When coupled with cas gene systems, CRISPR-Cas subtypes are highly site and taxon specific. Our analysis provides a comprehensive collection of natural CRISPR-cas loci and targets in the human microbiome.}, }
@article {pmid33211665, year = {2022}, author = {Kim, SA and Kang, N and Park, T}, title = {Hierarchical Structured Component Analysis for Microbiome Data Using Taxonomy Assignments.}, journal = {IEEE/ACM transactions on computational biology and bioinformatics}, volume = {19}, number = {3}, pages = {1302-1312}, doi = {10.1109/TCBB.2020.3039326}, pmid = {33211665}, issn = {1557-9964}, mesh = {Base Sequence ; Computer Simulation ; High-Throughput Nucleotide Sequencing/methods ; Humans ; *Microbiota/genetics ; Phylogeny ; }, abstract = {The recent advent of high-throughput sequencing technology has enabled us to study the associations between human microbiome and diseases. The DNA sequences of microbiome samples are clustered as operational taxonomic units (OTUs) according to their similarity. The OTU table containing counts of OTUs present in each sample is used to measure correlations between OTUs and disease status and find key microbes for prediction of the disease status. Various statistical methods have been proposed for such microbiome data analysis. However, none of these methods reflects the hierarchy of taxonomy information. In this paper, we propose a hierarchical structural component model for microbiome data (HisCoM-microb) using taxonomy information as well as OTU table data. The proposed HisCoM-microb consists of two layers: one for OTUs and the other for taxa at the higher taxonomy level. Then we calculate simultaneously coefficient estimates of OTUs and taxa of the two layers inserted in the hierarchical model. Through this analysis, we can infer the association between taxa or OTUs and disease status, considering the impact of taxonomic structure on disease status. Both simulation study and real microbiome data analysis show that HisCoM-microb can successfully reveal the relations between each taxon and disease status and identify the key OTUs of the disease at the same time.}, }
@article {pmid33208514, year = {2020}, author = {Hugerth, LW and Pereira, M and Zha, Y and Seifert, M and Kaldhusdal, V and Boulund, F and Krog, MC and Bashir, Z and Hamsten, M and Fransson, E and Svarre-Nielsen, H and Schuppe-Koistinen, I and Engstrand, L}, title = {Assessment of In Vitro and In Silico Protocols for Sequence-Based Characterization of the Human Vaginal Microbiome.}, journal = {mSphere}, volume = {5}, number = {6}, pages = {}, pmid = {33208514}, issn = {2379-5042}, mesh = {Computational Biology ; Computer Simulation ; Databases, Genetic ; Female ; Humans ; *Metagenome ; Metagenomics/*methods ; *Microbiota ; RNA, Ribosomal, 16S/*genetics ; Sequence Analysis, DNA ; Vagina/*microbiology ; }, abstract = {The vaginal microbiome has been connected to a wide range of health outcomes. This has led to a thriving research environment but also to the use of conflicting methodologies to study its microbial composition. Here, we systematically assessed best practices for the sequencing-based characterization of the human vaginal microbiome. As far as 16S rRNA gene sequencing is concerned, the V1-V3 region performed best in silico, but limitations of current sequencing technologies meant that the V3-V4 region performed equally well. Both approaches presented very good agreement with qPCR quantification of key taxa, provided that an appropriate bioinformatic pipeline was used. Shotgun metagenomic sequencing presents an interesting alternative to 16S rRNA gene amplification and sequencing but requires deeper sequencing and more bioinformatic expertise and infrastructure. We assessed different tools for the removal of host reads and the taxonomic annotation of metagenomic reads, including a new, easy-to-build and -use reference database of vaginal taxa. This curated database performed as well as the best-performing previously published strategies. Despite the many advantages of shotgun sequencing, none of the shotgun approaches assessed here agreed with the qPCR data as well as the 16S rRNA gene sequencing.IMPORTANCE The vaginal microbiome has been connected to various aspects of host health, including susceptibility to sexually transmitted infections as well as gynecological cancers and pregnancy outcomes. This has led to a thriving research environment but also to conflicting available methodologies, including many studies that do not report their molecular biological and bioinformatic methods in sufficient detail to be considered reproducible. This can lead to conflicting messages and delay progress from descriptive to intervention studies. By systematically assessing best practices for the characterization of the human vaginal microbiome, this study will enable past studies to be assessed more critically and assist future studies in the selection of appropriate methods for their specific research questions.}, }
@article {pmid33207573, year = {2020}, author = {Tsai, JC and Casteneda, G and Lee, A and Dereschuk, K and Li, WT and Chakladar, J and Lombardi, AF and Ongkeko, WM and Chang, EY}, title = {Identification and Characterization of the Intra-Articular Microbiome in the Osteoarthritic Knee.}, journal = {International journal of molecular sciences}, volume = {21}, number = {22}, pages = {}, pmid = {33207573}, issn = {1422-0067}, support = {I01RX002604//U.S. Department of Veterans Affairs/ ; R21AR073496/NH/NIH HHS/United States ; R01AR075825/NH/NIH HHS/United States ; I01CX001388//U.S. Department of Veterans Affairs/ ; I01 RX002604/RX/RRD VA/United States ; R21 AR073496/AR/NIAMS NIH HHS/United States ; R01 AR075825/AR/NIAMS NIH HHS/United States ; }, mesh = {*Bacteria/classification/genetics/metabolism ; Humans ; Knee Joint/*microbiology ; *Microbiota ; Osteoarthritis, Knee/*microbiology ; RNA-Seq ; Synovial Membrane/*microbiology ; }, abstract = {Osteoarthritis (OA) is the most common joint disorder in the United States, and the gut microbiome has recently emerged as a potential etiologic factor in OA development. Recent studies have shown that a microbiome is present at joint synovia. Therefore, we aimed to characterize the intra-articular microbiome within osteoarthritic synovia and to illustrate its role in OA disease progression. RNA-sequencing data from OA patient synovial tissue was aligned to a library of microbial reference genomes to identify microbial reads indicative of microbial abundance. Microbial abundance data of OA and normal samples was compared to identify differentially abundant microbes. We computationally explored the correlation of differentially abundant microbes to immunological gene signatures, immune signaling pathways, and immune cell infiltration. We found that microbes correlated to OA are related to dysregulation of two main functional pathways: increased inflammation-induced extracellular matrix remodeling and decreased cell signaling pathways crucial for joint and immune function. We also confirmed that the differentially abundant and biologically relevant microbes we had identified were not contaminants. Collectively, our findings contribute to the understanding of the human microbiome, well-known OA risk factors, and the role microbes play in OA pathogenesis. In conclusion, we present previously undiscovered microbes implicated in the OA disease progression that may be useful for future treatment purposes.}, }
@article {pmid33205871, year = {2020}, author = {Perttu, L and Jonna, J and Anna, H and Eero, M and Markku, H and Jari, P and Jari, K and Veli-Jukka, A and Jyrki, T and Reetta, S and Perttu, A}, title = {Letter: faecal microbiota transplantation for irritable bowel syndrome-which improvements are required? Authors' reply.}, journal = {Alimentary pharmacology &amp; therapeutics}, volume = {52}, number = {11-12}, pages = {1754-1755}, doi = {10.1111/apt.16122}, pmid = {33205871}, issn = {1365-2036}, mesh = {*Fecal Microbiota Transplantation ; Feces ; Humans ; *Irritable Bowel Syndrome/therapy ; }, }
@article {pmid33205072, year = {2020}, author = {Al, KF and Denstedt, JD and Daisley, BA and Bjazevic, J and Welk, BK and Pautler, SE and Gloor, GB and Reid, G and Razvi, H and Burton, JP}, title = {Ureteral Stent Microbiota Is Associated with Patient Comorbidities but Not Antibiotic Exposure.}, journal = {Cell reports. Medicine}, volume = {1}, number = {6}, pages = {100094}, pmid = {33205072}, issn = {2666-3791}, mesh = {Adult ; Anti-Bacterial Agents/pharmacology ; Canada/epidemiology ; Comorbidity ; Device Removal ; Female ; Humans ; Male ; Microbiota/genetics/physiology ; Middle Aged ; Stents/*adverse effects/*microbiology ; Ureter/*microbiology ; }, abstract = {Ureteral stents are commonly used to prevent urinary obstruction but can become colonized by bacteria and encrusted, leading to clinical complications. Despite recent discovery and characterization of the healthy urinary microbiota, stent-associated bacteria and their impact on encrustation are largely underexplored. We profile the microbiota of patients with typical short-term stents, as well as over 30 atypical cases (all with paired mid-stream urine) from 241 patients. Indwelling time, age, and various patient comorbidities correlate with alterations to the stent microbiota composition, whereas antibiotic exposure, urinary tract infection (UTI), and stent placement method do not. The stent microbiota most likely originates from adhesion of resident urinary microbes but subsequently diverges to a distinct, reproducible population, thereby negating the urine as a biomarker for stent encrustation or microbiota. Urological practice should reconsider standalone prophylactic antibiotics in favor of tailored therapies based on patient comorbidities in efforts to minimize bacterial burden, encrustation, and complications of ureteral stents.}, }
@article {pmid33203758, year = {2020}, author = {Patin, NV and Peña-Gonzalez, A and Hatt, JK and Moe, C and Kirby, A and Konstantinidis, KT}, title = {The Role of the Gut Microbiome in Resisting Norovirus Infection as Revealed by a Human Challenge Study.}, journal = {mBio}, volume = {11}, number = {6}, pages = {}, pmid = {33203758}, issn = {2150-7511}, support = {K01 AI103544/AI/NIAID NIH HHS/United States ; R01 AI137679/AI/NIAID NIH HHS/United States ; }, mesh = {Asymptomatic Diseases ; Bacteroidetes/genetics/*growth &amp; development ; Caliciviridae Infections/immunology/*prevention &amp; control/virology ; Disease Susceptibility ; Firmicutes/genetics/*growth &amp; development ; *Gastrointestinal Microbiome ; Humans ; Metagenomics ; Norovirus/*immunology ; Proteobacteria/genetics/*growth &amp; development ; }, abstract = {Norovirus infections take a heavy toll on worldwide public health. While progress has been made toward understanding host responses to infection, the role of the gut microbiome in determining infection outcome is unknown. Moreover, data are lacking on the nature and duration of the microbiome response to norovirus infection, which has important implications for diagnostics and host recovery. Here, we characterized the gut microbiomes of subjects enrolled in a norovirus challenge study. We analyzed microbiome features of asymptomatic and symptomatic individuals at the genome (population) and gene levels and assessed their response over time in symptomatic individuals. We show that the preinfection microbiomes of subjects with asymptomatic infections were enriched in Bacteroidetes and depleted in Clostridia relative to the microbiomes of symptomatic subjects. These compositional differences were accompanied by differences in genes involved in the metabolism of glycans and sphingolipids that may aid in host resilience to infection. We further show that microbiomes shifted in composition following infection and that recovery times were variable among human hosts. In particular, Firmicutes increased immediately following the challenge, while Bacteroidetes and Proteobacteria decreased over the same time. Genes enriched in the microbiomes of symptomatic subjects, including the adenylyltransferase glgC, were linked to glycan metabolism and cell-cell signaling, suggesting as-yet unknown roles for these processes in determining infection outcome. These results provide important context for understanding the gut microbiome role in host susceptibility to symptomatic norovirus infection and long-term health outcomes.IMPORTANCE The role of the human gut microbiome in determining whether an individual infected with norovirus will be symptomatic is poorly understood. This study provides important data on microbes that distinguish asymptomatic from symptomatic microbiomes and links these features to infection responses in a human challenge study. The results have implications for understanding resistance to and treatment of norovirus infections.}, }
@article {pmid33203357, year = {2020}, author = {Ma, Y and Zhao, J and Ma, Y}, title = {MHSNMF: multi-view hessian regularization based symmetric nonnegative matrix factorization for microbiome data analysis.}, journal = {BMC bioinformatics}, volume = {21}, number = {Suppl 6}, pages = {234}, pmid = {33203357}, issn = {1471-2105}, mesh = {*Algorithms ; Cluster Analysis ; *Data Analysis ; Humans ; *Microbiota ; Phylogeny ; }, abstract = {BACKGROUND: With the rapid development of high-throughput technique, multiple heterogeneous omics data have been accumulated vastly (e.g., genomics, proteomics and metabolomics data). Integrating information from multiple sources or views is challenging to obtain a profound insight into the complicated relations among micro-organisms, nutrients and host environment. In this paper we propose a multi-view Hessian regularization based symmetric nonnegative matrix factorization algorithm (MHSNMF) for clustering heterogeneous microbiome data. Compared with many existing approaches, the advantages of MHSNMF lie in: (1) MHSNMF combines multiple Hessian regularization to leverage the high-order information from the same cohort of instances with multiple representations; (2) MHSNMF utilities the advantages of SNMF and naturally handles the complex relationship among microbiome samples; (3) uses the consensus matrix obtained by MHSNMF, we also design a novel approach to predict the classification of new microbiome samples.<br><br>RESULTS: We conduct extensive experiments on two real-word datasets (Three-source dataset and Human Microbiome Plan dataset), the experimental results show that the proposed MHSNMF algorithm outperforms other baseline and state-of-the-art methods. Compared with other methods, MHSNMF achieves the best performance (accuracy: 95.28%, normalized mutual information: 91.79%) on microbiome data. It suggests the potential application of MHSNMF in microbiome data analysis.<br><br>CONCLUSIONS: Results show that the proposed MHSNMF algorithm can effectively combine the phylogenetic, transporter, and metabolic profiles into a unified paradigm to analyze the relationships among different microbiome samples. Furthermore, the proposed prediction method based on MHSNMF has been shown to be effective in judging the types of new microbiome samples.}, }
@article {pmid33198235, year = {2020}, author = {van Soest, APM and Hermes, GDA and Berendsen, AAM and van de Rest, O and Zoetendal, EG and Fuentes, S and Santoro, A and Franceschi, C and de Groot, LCPGM and de Vos, WM}, title = {Associations between Pro- and Anti-Inflammatory Gastro-Intestinal Microbiota, Diet, and Cognitive Functioning in Dutch Healthy Older Adults: The NU-AGE Study.}, journal = {Nutrients}, volume = {12}, number = {11}, pages = {}, pmid = {33198235}, issn = {2072-6643}, support = {266486//Seventh Framework Programme/ ; 818368//Horizon 2020 Framework Programme/ ; n/a//Spinoza award of The Netherlands Organization for Scientific Research 2008/ ; }, mesh = {Aged ; Bacteria/isolation &amp; purification ; *Cognition ; *Diet, Mediterranean ; Feces/*microbiology ; Female ; *Gastrointestinal Microbiome ; Healthy Volunteers ; Humans ; Male ; Netherlands ; RNA, Ribosomal, 16S/genetics ; }, abstract = {Dietary modulation of the gastro-intestinal microbiota is a potential target in improving healthy ageing and age-related functional outcomes, including cognitive decline. We explored the association between diet, gastro-intestinal microbiota and cognition in Dutch healthy older adults of the 'New dietary strategies addressing the specific needs of the elderly population for healthy aging in Europe' (NU-AGE) study. The microbiota profile of 452 fecal samples from 226 subjects was determined using a 16S ribosomal RNA gene-targeted microarray. Dietary intake was assessed by 7-day food records. Cognitive functioning was measured with an extensive cognitive test battery. We observed a dietary and microbial pro- to anti-inflammatory gradient associated with diets richer in animal- or plant-based foods. Fresh fruits, nuts, seeds and peanuts, red and processed meat and grain products were most strongly associated to microbiota composition. Plant-rich diets containing fresh fruits, nuts, seeds and peanuts were positively correlated with alpha-diversity, various taxa from the Bacteroidetes phylum and anti-inflammatory species, including those related to Faecalibacterium prausnitzii and Eubacterium rectale and E. biforme. Animal product-rich diets associated with pro-inflammatory species, including those related to Ruminococcus gnavus and Collinsella spp.. Cognition was neither associated with microbiota composition nor alpha-diversity. In conclusion, diets richer in animal- and plant-based foods were related to a pro- and anti-inflammatory microbial profile, while cognition was associated with neither.}, }
@article {pmid33198059, year = {2020}, author = {Krishnamoorthy, M and Lenehan, JG and Burton, JP and Maleki Vareki, S}, title = {Immunomodulation in Pancreatic Cancer.}, journal = {Cancers}, volume = {12}, number = {11}, pages = {}, pmid = {33198059}, issn = {2072-6694}, support = {N/A//London Regional Cancer Program's Catalyst Grant Program, Keith Smitt Translational Research Grants./ ; }, abstract = {Pancreatic cancer has a high mortality rate, and its incidence is increasing worldwide. The almost universal poor prognosis of pancreatic cancer is partly due to symptoms presenting only at late stages and limited effective treatments. Recently, immune checkpoint blockade inhibitors have drastically improved patient survival in metastatic and advanced settings in certain cancers. Unfortunately, these therapies are ineffective in pancreatic cancer. However, tumor biopsies from long-term survivors of pancreatic cancer are more likely to be infiltrated by cytotoxic T-cells and certain species of bacteria that activate T-cells. These observations suggest that T-cell activation is essential for anti-tumor immunity in pancreatic cancers. This review discusses the immunological mechanisms responsible for effective anti-tumor immunity and how immune-based strategies can be exploited to develop new pancreatic cancer treatments.}, }
@article {pmid33197547, year = {2021}, author = {Collins, SL and Walsh, JP and Renaud, JB and McMillan, A and Rulisa, S and Miller, JD and Reid, G and Sumarah, MW}, title = {Improved methods for biomarker analysis of the big five mycotoxins enables reliable exposure characterization in a population of childbearing age women in Rwanda.}, journal = {Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association}, volume = {147}, number = {}, pages = {111854}, doi = {10.1016/j.fct.2020.111854}, pmid = {33197547}, issn = {1873-6351}, mesh = {Adult ; Biomarkers/blood ; Female ; *Food Contamination ; Humans ; Mycotoxins/blood/chemistry/*toxicity ; Pregnancy ; Pregnancy Complications/*chemically induced/prevention &amp; control ; Rwanda ; }, abstract = {Of the five agriculturally important mycotoxins, AFB1, FB1, DON, ZEA and OTA, a well-characterized biomarker of exposure in blood is only available for aflatoxin. Working with a population of 139 women of childbearing age in Rwanda, we undertook a comprehensive assessment of their dietary mycotoxin exposure. Using high-resolution LC-MS/MS with stable isotope dilution analysis, the albumin-aflatoxin adduct was quantitated in plasma. Similarly, AFM1, AFB1, AFG1, FB1 and B2, OTA, zearalenone, α-zearalenol, deoxynivalenol, deoxynivalenol-15-glucuronide and deoxynivalenol-3-glucuronide were quantitated in urine. AFB1-Lys was detected in plasma from 81% of the women, indicative of exposures 1-2 orders of magnitude above current guidance. Zearalenone and/or α-zearalenol were detected in the urine of 61% of the women, the majority of whom had estimated exposures 2-5 times the PMTDI, with one third more than an order of magnitude above. Urinary deoxynivalenol or the two glucuronide conjugates were found in 77% of the participants. Of these, 60% were below the PMTDI, 28% were twice and 12% were >10x the PMTDI. Fumonisin B1 (30%) and ochratoxin A (71%) were also detected in urine. Exposures observed in these Rwandan women raise serious food safety concerns and highlight the need for authorities to help manage multiple mycotoxins in their diet.}, }
@article {pmid33193429, year = {2020}, author = {Irfan, M and Delgado, RZR and Frias-Lopez, J}, title = {The Oral Microbiome and Cancer.}, journal = {Frontiers in immunology}, volume = {11}, number = {}, pages = {591088}, pmid = {33193429}, issn = {1664-3224}, support = {R01 DE021553/DE/NIDCR NIH HHS/United States ; }, mesh = {Animals ; Combined Modality Therapy/methods ; Disease Management ; *Disease Susceptibility ; Host-Pathogen Interactions ; Humans ; *Microbiota ; *Mouth Mucosa ; Mouth Neoplasms/etiology ; Neoplasms/diagnosis/*etiology/therapy ; Organ Specificity ; Squamous Cell Carcinoma of Head and Neck/etiology ; Treatment Outcome ; }, abstract = {There is mounting evidence that members of the human microbiome are highly associated with a wide variety of cancer types. Among oral cancers, oral squamous cell carcinoma (OSCC) is the most prevalent and most commonly studied, and it is the most common malignancy of the head and neck worldwide. However, there is a void regarding the role that the oral microbiome may play in OSCC. Previous studies have not consistently found a characteristic oral microbiome composition associated with OSCC. Although a direct causality has not been proven, individual members of the oral microbiome are capable of promoting various tumorigenic functions related to cancer development. Two prominent oral pathogens, Porphyromonas gingivalis, and Fusobacterium nucleatum can promote tumor progression in mice. P. gingivalis infection has been associated with oro-digestive cancer, increased oral cancer invasion, and proliferation of oral cancer stem cells. The microbiome can influence the evolution of the disease by directly interacting with the human body and significantly altering the response and toxicity to various forms of cancer therapy. Recent studies have shown an association of certain phylogenetic groups with the immunotherapy treatment outcomes of certain tumors. On the other side of the coin, recently it has been a resurgence in interest on the potential use of bacteria to cure cancer. These kinds of treatments were used in the late nineteenth and early twentieth centuries as the first line of defense against cancer in some hospitals but later displaced by other types of treatments such as radiotherapy. Currently, organisms such as Salmonella typhimurium and Clostridium spp. have been used for targeted strategies as potential vectors to treat cancer. In this review, we briefly summarize our current knowledge of the role of the oral microbiome, focusing on its bacterial fraction, in cancer in general and in OSCC more precisely, and a brief description of the potential use of bacteria to target tumors.}, }
@article {pmid33193202, year = {2020}, author = {Petrie, KL}, title = {There're CRISPRs in My Yogurt: A Discovery-Based CURE at the Intersection of Industrial Food Production and the Human Microbiome.}, journal = {Frontiers in microbiology}, volume = {11}, number = {}, pages = {578737}, pmid = {33193202}, issn = {1664-302X}, abstract = {Support for undergraduate laboratory education based on a CURE (Course-based Undergraduate Research Experience) model is more widespread than ever. By giving students the opportunity to conduct genuine research in laboratory courses they are required to take, CUREs can expose more students to scientific practice and have the potential to make science more inclusive, especially when research topics have direct impact on students' lives. Here, I present a new microbiology CURE module where students explore the real-world intersection between industrial food production and the human microbiome. In this module, students sequence CRISPR arrays in the genomes of lactic acid bacteria they isolate from yogurt. Natural CRISPRs (Clustered Regularly Interspaced Short Palindromic Repeats) act as the bacterial immune system. When a bacterial cell survives viral infection, it can incorporate a bit of that virus's DNA into its own genome, and produce small RNA guides that surveil the cell, ready to deploy virus-destroying enzymes if matching DNA from a fresh viral infection is detected. This viral immunity is of particular interest in the fermentation industry, since viral infection can destroy stocks of starter cultures and batches of product. Commercial producers of lactic acid bacteria for yogurt production often endeavor to produce strains with large CRISPR arrays and robust immunities. With this context, students are given the task of cataloging the viral immunities found in both commercial and traditionally produced yogurt, and exploring their potential impact on human health. Wet-lab practices (strain isolation, PCR, and Sanger sequencing) are combined with bioinformatic and literature sleuthing to identify the viruses to which bacteria are immune and explore whether consumption of these strains could impact human health via interactions with the human microbiome. Here, a detailed implementation of the module is presented with guides for educators and students.}, }
@article {pmid33188000, year = {2021}, author = {Coe, GL and Pinkham, NV and Celis, AI and Johnson, C and DuBois, JL and Walk, ST}, title = {Dynamic Gut Microbiome Changes in Response to Low-Iron Challenge.}, journal = {Applied and environmental microbiology}, volume = {87}, number = {3}, pages = {}, pmid = {33188000}, issn = {1098-5336}, support = {R01 GM086755/GM/NIGMS NIH HHS/United States ; R21 DK114607/DK/NIDDK NIH HHS/United States ; R35 GM136390/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Bacteria/drug effects/genetics/isolation &amp; purification ; Feces/chemistry ; Female ; Gastrointestinal Microbiome/*drug effects/genetics ; Iron/*administration &amp; dosage/blood/pharmacokinetics ; Male ; Mice, Inbred C57BL ; RNA, Ribosomal, 16S ; Mice ; }, abstract = {Iron is an essential micronutrient for life. In mammals, dietary iron is absorbed primarily in the small intestine. Currently, the impacts of dietary iron on the taxonomic structure and function of the gut microbiome and reciprocal effects on the animal host are not well understood. Here, we establish a mouse model of low-iron challenge in which intestinal biomarkers and reduced fecal iron reveal iron stress while serum iron and mouse behavioral markers indicate maintenance of iron homeostasis. We show that the diversity of the gut microbiome in conventional C57BL/6 mice changes dramatically during 2 weeks on a low-iron diet. We also show the effects of a low-iron diet on microbiome diversity are long lasting and not easily recovered when iron is returned to the diet. Finally, after optimizing taxon association methods, we show that some bacteria are unable to fully recover after the low-iron challenge and appear to be extirpated from the gut entirely. In particular, operational taxonomic units (OTUs) from the Prevotellaceae and Porphyromonadaceae families and Bacteroidales order are highly sensitive to low-iron conditions, while other seemingly insensitive OTUs recover. These results provide new insights into the iron requirements of gut microbiome members and add to the growing understanding of mammalian iron cycling.IMPORTANCE All cells need iron. Both too much and too little iron lead to diseases and unwanted outcomes. Although the impact of dietary iron on human cells and tissues has been well studied, there is currently a lack of understanding about how different levels of iron influence the abundant and diverse members of the human microbiome. This study develops a well-characterized mouse model for studying low-iron levels and identifies key groups of bacteria that are most affected. We found that the microbiome undergoes large changes when iron is removed from the diet but that many individual bacteria are able to rebound when iron levels are changed back to normal. That said, a select few members, referred to as iron-sensitive bacteria, seem to be lost. This study begins to identify individual members of the mammalian microbiome most affected by changes in dietary iron levels.}, }
@article {pmid33182444, year = {2020}, author = {A James, S and Phillips, S and Telatin, A and Baker, D and Ansorge, R and Clarke, P and J Hall, L and R Carding, S}, title = {Preterm Infants Harbour a Rapidly Changing Mycobiota That Includes Candida Pathobionts.}, journal = {Journal of fungi (Basel, Switzerland)}, volume = {6}, number = {4}, pages = {}, pmid = {33182444}, issn = {2309-608X}, support = {BBS/E/F/00044409/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; BB/R012490//BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; BB/J004529/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; BBS/E/F/000PR10353, BBS/E/F/000PR10355 and BBS/E/F/000PR10356/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; BBS/E/F/000PR10355/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; BBS/E/F/000PR10353/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; BBS/E/F/000PR10356/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; 100974/C/13/Z/WT_/Wellcome Trust/United Kingdom ; }, abstract = {Fungi and the mycobiome are a fundamental part of the human microbiome that contributes to human health and development. Despite this, relatively little is known about the mycobiome of the preterm infant gut. Here, we have characterised faecal fungal communities present in 11 premature infants born with differing degrees of prematurity and mapped how the mycobiome develops during early infancy. Using an ITS1 sequencing-based approach, the preterm infant gut mycobiome was found to be often dominated by a single species, typically a yeast. Candida was the most abundant genus, with the pathobionts C.albicans and C.parapsilosis highly prevalent and persistent in these infants. Gestational maturity at birth affected the distribution and abundance of these Candida, with hospital-associated C.parapsilosis more prevalent and abundant in infants born at less than 31 weeks. Fungal diversity was lowest at 6 months, but increased with age and change of diet, with food-associated Saccharomycescerevisiae most abundant in infants post weaning. This study provides a first insight into the fungal communities present within the preterm infant gut, identifying distinctive features including the prominence of pathobiont species, and the influence age and environmental factors play in shaping the development of the mycobiome.}, }
@article {pmid33178777, year = {2020}, author = {Nicolaro, M and Portal, DE and Shinder, B and Patel, HV and Singer, EA}, title = {The human microbiome and genitourinary malignancies.}, journal = {Annals of translational medicine}, volume = {8}, number = {19}, pages = {1245}, pmid = {33178777}, issn = {2305-5839}, support = {P30 CA072720/CA/NCI NIH HHS/United States ; }, abstract = {The human microbiome contains a vast network of understudied organisms that have an intimate role in our health and wellness. These microbiomes differ greatly between individuals, creating what may be thought of as a unique and dynamic microbial signature. Microbes have been shown to have various roles in metabolism, local and systemic inflammation, as well as immunity. Recent findings have confirmed the importance of both the gut and urinary microbiomes in genitourinary malignancies. Numerous studies have identified differences in microbial signatures between healthy patients and those with urologic malignancies. The microbiomes have been shown to contain microbes that may contribute to the etiology of disease state as well as yield information in regard to a person's health and their responsiveness to certain drugs such as immune checkpoint inhibitors (ICIs) and tyrosine kinase inhibitors (TKIs). Less well understood are the effects of antibiotics on oncologic outcomes in such treatment courses. This review will explore our current understanding and advancements in the field of microbiome research and discuss its intimate association with genitourinary diseases including bladder cancer, prostate cancer, and kidney cancer. With a better understanding of the association between the microbiome and genitourinary malignancy, further investigation may produce reliable predictors of disease, prognostic indicators as well as therapeutic targets.}, }
@article {pmid33178428, year = {2020}, author = {Sikakana, P and Roberts, RA}, title = {A decade of toxicological trends: what the papers say.}, journal = {Toxicology research}, volume = {9}, number = {5}, pages = {676-682}, pmid = {33178428}, issn = {2045-452X}, abstract = {Here we look at popular trends and concepts in toxicology over the decade 2009-2019. The top 10 concepts included methodological approaches such as zebrafish and genomics as well as broader concepts such as personalized medicine and adverse outcome pathways. The total number and rank order for each of the top 10 were tracked year by year via PubMed with >9500 papers contributing to the analysis. The data revealed a slow upward trend in the number of papers across all the concepts from 260 in 2009 to >1700 in 2019. Zebrafish, genomics and personalized medicine remained in the top four slots since 2009 with zebrafish dominating the rankings over the entire decade. Genomics was a strong second until 2013 when it was displaced first by the microbiome in 2014 and secondly by personalized medicine in 2015. Other notable trends were the ascendancy of the microbiome and adverse outcome pathways and the descendancy of hormesis and the 3Rs (replacement, reduction and refinement of animals in testing). The observation that the top four slots have been static over the past 4 years suggests that new ideas are introduced and increase in popularity until they find their place in scientific culture. This may suggest that relatively new concepts such as artificial intelligence and microphysiological systems have yet to find their steady state in the rankings. Similarly, as a relatively new player in toxicology, the full impact of the human microbiome on drug efficacy and safety remains to be seen.}, }
@article {pmid33177184, year = {2020}, author = {Stokholm, J and Thorsen, J and Blaser, MJ and Rasmussen, MA and Hjelmsø, M and Shah, S and Christensen, ED and Chawes, BL and Bønnelykke, K and Brix, S and Mortensen, MS and Brejnrod, A and Vestergaard, G and Trivedi, U and Sørensen, SJ and Bisgaard, H}, title = {Delivery mode and gut microbial changes correlate with an increased risk of childhood asthma.}, journal = {Science translational medicine}, volume = {12}, number = {569}, pages = {}, doi = {10.1126/scitranslmed.aax9929}, pmid = {33177184}, issn = {1946-6242}, mesh = {*Asthma ; Cesarean Section ; Child ; Female ; *Gastrointestinal Microbiome ; Humans ; Pregnancy ; Prospective Studies ; RNA, Ribosomal, 16S/genetics ; }, abstract = {There have been reports of associations between cesarean section delivery and the risk of childhood asthma, potentially mediated through changes in the gut microbiota. We followed 700 children in the Copenhagen Prospective Studies on Asthma in Childhood2010 (COPSAC2010) cohort prospectively from birth. We examined the effects of cesarean section delivery on gut microbial composition by 16S rRNA gene amplicon sequencing during the first year of life. We then explored whether gut microbial perturbations due to delivery mode were associated with a risk of developing asthma in the first 6 years of life. Delivery by cesarean section was accompanied by marked changes in gut microbiota composition at one week and one month of age, but by one year of age only minor differences persisted compared to vaginal delivery. Increased asthma risk was found in children born by cesarean section only if their gut microbiota composition at 1 year of age still retained a cesarean section microbial signature, suggesting that appropriate maturation of the gut microbiota could mitigate against the increased asthma risk associated with gut microbial changes due to cesarean section delivery.}, }
@article {pmid33176111, year = {2021}, author = {Hadrup, N and Aimonen, K and Ilves, M and Lindberg, H and Atluri, R and Sahlgren, NM and Jacobsen, NR and Barfod, KK and Berthing, T and Lawlor, A and Norppa, H and Wolff, H and Jensen, KA and Hougaard, KS and Alenius, H and Catalan, J and Vogel, U}, title = {Pulmonary toxicity of synthetic amorphous silica - effects of porosity and copper oxide doping.}, journal = {Nanotoxicology}, volume = {15}, number = {1}, pages = {96-113}, doi = {10.1080/17435390.2020.1842932}, pmid = {33176111}, issn = {1743-5404}, mesh = {Acute-Phase Reaction ; Animals ; Comet Assay ; Copper/chemistry/*toxicity ; DNA Damage ; Mice ; Micronucleus Tests ; Nanoparticles/chemistry/*toxicity ; Nanostructures ; Pilot Projects ; Pneumonia/*chemically induced/pathology ; Porosity ; Silicon Dioxide/*chemistry/*toxicity ; }, abstract = {Materials can be modified for improved functionality. Our aim was to test whether pulmonary toxicity of silica nanomaterials is increased by the introduction of: a) porosity; and b) surface doping with CuO; and whether c) these modifications act synergistically. Mice were exposed by intratracheal instillation and for some doses also oropharyngeal aspiration to: 1) solid silica 100 nm; 2) porous silica 100 nm; 3) porous silica 100 nm with CuO doping; 4) solid silica 300 nm; 5) porous silica 300 nm; 6) solid silica 300 nm with CuO doping; 7) porous silica 300 nm with CuO doping; 8) CuO nanoparticles 9.8 nm; or 9) carbon black Printex 90 as benchmark. Based on a pilot study, dose levels were between 0.5 and 162 µg/mouse (0.2 and 8.1 mg/kg bw). Endpoints included pulmonary inflammation (neutrophil numbers in bronchoalveolar fluid), acute phase response, histopathology, and genotoxicity assessed by the comet assay, micronucleus test, and the gamma-H2AX assay. The porous silica materials induced greater pulmonary inflammation than their solid counterparts. A similar pattern was seen for acute phase response induction and histologic changes. This could be explained by a higher specific surface area per mass unit for the most toxic particles. CuO doping further increased the acute phase response normalized according to the deposited surface area. We identified no consistent evidence of synergism between surface area and CuO doping. In conclusion, porosity and CuO doping each increased the toxicity of silica nanomaterials and there was no indication of synergy when the modifications co-occurred.}, }
@article {pmid33172400, year = {2020}, author = {Brandt, K and Barrangou, R}, title = {Adaptive response to iterative passages of five Lactobacillus species in simulated vaginal fluid.}, journal = {BMC microbiology}, volume = {20}, number = {1}, pages = {339}, pmid = {33172400}, issn = {1471-2180}, mesh = {*Adaptation, Physiological/genetics ; Body Fluids/chemistry/*microbiology ; Female ; Genome, Bacterial ; Genomic Instability ; Humans ; Lactobacillus/classification/genetics/growth &amp; development/*physiology ; Species Specificity ; Transcriptome ; Vagina/chemistry/*microbiology ; }, abstract = {BACKGROUND: Microbiome and metagenomic studies have given rise to a new understanding of microbial colonization of various human tissues and their ability to impact our health. One human microbiome growing in notoriety, the vaginal microbiome, stands out given its importance for women's health, and is peculiar in terms of its relative bacterial composition, including its simplicity and typical domination by a small number of Lactobacillus species. The loss of Lactobacillus dominance is associated with disorders such as bacterial vaginosis, and efforts are now underway to understand the ability of Lactobacillus species to colonize the vaginal tract and adapt to this dynamic and acidic environment. Here, we investigate how various Lactobacillus species often isolated from the vaginal and intestinal cavities genomically and transcriptionally respond to iterative growth in simulated vaginal fluid.<br><br>RESULTS: We determined the genomes and transcriptomes of L. acidophilus, L. crispatus, L. fermentum, L. gasseri, and L. jensenii and compared profiles after 50, 100, 500, and 1000 generations of iterative passages in synthetic vaginal fluid. In general, we identified relatively few genetic changes consisting of single nucleotide polymorphisms, with higher counts occurring more frequently in non-vaginal isolated species. Transcriptional profiles were more impacted over time and tended to be more extensive for species that typically do not dominate the vaginal tract, reflecting a more extensive need to adapt to a less familiar environment.<br><br>CONCLUSIONS: This study provides insights into how vaginal and non-vaginal Lactobacillus species respond and adapt to a simulated vaginal environment. Overall, trends indicate high genomic stability for all species involved, with more variability in the transcriptome especially for non-dominant species of the vaginal tract.}, }
@article {pmid33166356, year = {2020}, author = {Zhang, X and Guo, B and Yi, N}, title = {Zero-Inflated gaussian mixed models for analyzing longitudinal microbiome data.}, journal = {PloS one}, volume = {15}, number = {11}, pages = {e0242073}, pmid = {33166356}, issn = {1932-6203}, mesh = {Algorithms ; Bacteria/genetics/isolation &amp; purification ; Bacterial Load ; Computer Simulation ; Dysbiosis/microbiology ; Humans ; Longitudinal Studies ; *Microbiota ; Normal Distribution ; RNA, Ribosomal, 16S/genetics ; Software ; }, abstract = {MOTIVATION: The human microbiome is variable and dynamic in nature. Longitudinal studies could explain the mechanisms in maintaining the microbiome in health or causing dysbiosis in disease. However, it remains challenging to properly analyze the longitudinal microbiome data from either 16S rRNA or metagenome shotgun sequencing studies, output as proportions or counts. Most microbiome data are sparse, requiring statistical models to handle zero-inflation. Moreover, longitudinal design induces correlation among the samples and thus further complicates the analysis and interpretation of the microbiome data.<br><br>RESULTS: In this article, we propose zero-inflated Gaussian mixed models (ZIGMMs) to analyze longitudinal microbiome data. ZIGMMs is a robust and flexible method which can be applicable for longitudinal microbiome proportion data or count data generated with either 16S rRNA or shotgun sequencing technologies. It can include various types of fixed effects and random effects and account for various within-subject correlation structures, and can effectively handle zero-inflation. We developed an efficient Expectation-Maximization (EM) algorithm to fit the ZIGMMs by taking advantage of the standard procedure for fitting linear mixed models. We demonstrate the computational efficiency of our EM algorithm by comparing with two other zero-inflated methods. We show that ZIGMMs outperform the previously used linear mixed models (LMMs), negative binomial mixed models (NBMMs) and zero-inflated Beta regression mixed model (ZIBR) in detecting associated effects in longitudinal microbiome data through extensive simulations. We also apply our method to two public longitudinal microbiome datasets and compare with LMMs and NBMMs in detecting dynamic effects of associated taxa.}, }
@article {pmid33163830, year = {2020}, author = {Witjes, JJ and Smits, LP and Pekmez, CT and Prodan, A and Meijnikman, AS and Troelstra, MA and Bouter, KEC and Herrema, H and Levin, E and Holleboom, AG and Winkelmeijer, M and Beuers, UH and van Lienden, K and Aron-Wisnewky, J and Mannisto, V and Bergman, JJ and Runge, JH and Nederveen, AJ and Dragsted, LO and Konstanti, P and Zoetendal, EG and de Vos, W and Verheij, J and Groen, AK and Nieuwdorp, M}, title = {Donor Fecal Microbiota Transplantation Alters Gut Microbiota and Metabolites in Obese Individuals With Steatohepatitis.}, journal = {Hepatology communications}, volume = {4}, number = {11}, pages = {1578-1590}, pmid = {33163830}, issn = {2471-254X}, abstract = {The intestinal microbiota has been linked to the development and prevalence of steatohepatitis in humans. Interestingly, steatohepatitis is significantly lower in individuals taking a plant-based, low-animal-protein diet, which is thought to be mediated by gut microbiota. However, data on causality between these observations in humans is scarce. In this regard, fecal microbiota transplantation (FMT) using healthy donors is safe and is capable of changing microbial composition in human disease. We therefore performed a double-blind randomized controlled proof-of-principle study in which individuals with hepatic steatosis on ultrasound were randomized to two study arms: lean vegan donor (allogenic n = 10) or own (autologous n = 11) FMT. Both were performed three times at 8-week intervals. A liver biopsy was performed at baseline and after 24 weeks in every subject to determine histopathology (Nonalcoholic Steatohepatitis Clinical Research Network) classification and changes in hepatic gene expression based on RNA sequencing. Secondary outcome parameters were changes in intestinal microbiota composition and fasting plasma metabolomics. We observed a trend toward improved necro-inflammatory histology, and found significant changes in expression of hepatic genes involved in inflammation and lipid metabolism following allogenic FMT. Intestinal microbial community structure changed following allogenic FMT, which was associated with changes in plasma metabolites as well as markers of . Conclusion: Allogenic FMT using lean vegan donors in individuals with hepatic steatosis shows an effect on intestinal microbiota composition, which is associated with beneficial changes in plasma metabolites and markers of steatohepatitis.}, }
@article {pmid33158018, year = {2020}, author = {Zizzari, IG and Di Filippo, A and Scirocchi, F and Di Pietro, FR and Rahimi, H and Ugolini, A and Scagnoli, S and Vernocchi, P and Del Chierico, F and Putignani, L and Rughetti, A and Marchetti, P and Nuti, M and Botticelli, A and Napoletano, C}, title = {Soluble Immune Checkpoints, Gut Metabolites and Performance Status as Parameters of Response to Nivolumab Treatment in NSCLC Patients.}, journal = {Journal of personalized medicine}, volume = {10}, number = {4}, pages = {}, pmid = {33158018}, issn = {2075-4426}, support = {IG grant 2015 n&#xb0;17432//Associazione Italiana per la Ricerca sul Cancro/International ; RM118164277B5F2A//Ministero dell'Istruzione, dell'Universit&#xe0; e della Ricerca/International ; RM1181643132016E//Ministero dell'Istruzione, dell'Universit&#xe0; e della Ricerca/International ; }, abstract = {Patients with non-small cell lung cancer (NSCLC) have been shown to benefit from the introduction of anti-PD1 treatment. However, not all patients experience tumor regression and durable response. The identification of a string of markers that are direct or indirect indicators of the immune system fitness is needed to choose optimal therapeutic schedules in the management of NSCLC patients. We analyzed 34 immuno-related molecules (14 soluble immune checkpoints, 17 cytokines/chemokines, 3 adhesion molecules) released in the serum of 22 NSCLC patients under Nivolumab treatment and the gut metabolomic profile at baseline. These parameters were correlated with performance status (PS) and/or response to treatment. Nivolumab affected the release of soluble immune checkpoints (sICs). Patients with a better clinical outcome and with an optimal PS (PS = 0) showed a decreased level of PD1 and maintained low levels of several sICs at first clinical evaluation. Low levels of PDL1, PDL2, Tim3, CD137 and BTLA4 were also correlated with a long response to treatment. Moreover, responding patients showed a high proportion of eubiosis-associated gut metabolites. In this exploratory study, we propose a combination of immunological and clinical parameters (sICs, PS and gut metabolites) for the identification of patients more suitable for Nivolumab treatment. This string of parameters validated in a network analysis on a larger cohort of patients could help oncologists to improve their decision-making in an NSCLC setting.}, }
@article {pmid33155101, year = {2021}, author = {Torralba, MG and Aleti, G and Li, W and Moncera, KJ and Lin, YH and Yu, Y and Masternak, MM and Golusinski, W and Golusinski, P and Lamperska, K and Edlund, A and Freire, M and Nelson, KE}, title = {Oral Microbial Species and Virulence Factors Associated with Oral Squamous Cell Carcinoma.}, journal = {Microbial ecology}, volume = {82}, number = {4}, pages = {1030-1046}, pmid = {33155101}, issn = {1432-184X}, support = {R00 DE023584/DE/NIDCR NIH HHS/United States ; }, mesh = {*Carcinoma, Squamous Cell ; *Head and Neck Neoplasms ; Humans ; *Mouth Neoplasms ; RNA, Ribosomal, 16S/genetics ; Squamous Cell Carcinoma of Head and Neck ; Virulence Factors/genetics ; }, abstract = {The human microbiome has been the focus of numerous research efforts to elucidate the pathogenesis of human diseases including cancer. Oral cancer mortality is high when compared with other cancers, as diagnosis often occurs during late stages. Its prevalence has increased in the USA over the past decade and accounts for over 40,000 new cancer patients each year. Additionally, oral cancer pathogenesis is not fully understood and is likely multifactorial. To unravel the relationships that are associated with the oral microbiome and their virulence factors, we used 16S rDNA and metagenomic sequencing to characterize the microbial composition and functional content in oral squamous cell carcinoma (OSCC) tumor tissue, non-tumor tissue, and saliva from 18 OSCC patients. Results indicate a higher number of bacteria belonging to the Fusobacteria, Bacteroidetes, and Firmicutes phyla associated with tumor tissue when compared with all other sample types. Additionally, saliva metaproteomics revealed a significant increase of Prevotella in five OSCC subjects, while Corynebacterium was mostly associated with ten healthy subjects. Lastly, we determined that there are adhesion and virulence factors associated with Streptococcus gordonii as well as from known oral pathogens belonging to the Fusobacterium genera found mostly in OSCC tissues. From these results, we propose that not only will the methods utilized in this study drastically improve OSCC diagnostics, but the organisms and specific virulence factors from the phyla detected in tumor tissue may be excellent biomarkers for characterizing disease progression.}, }
@article {pmid33151137, year = {2021}, author = {Keller, JJ and Ooijevaar, RE and Hvas, CL and Terveer, EM and Lieberknecht, SC and Högenauer, C and Arkkila, P and Sokol, H and Gridnyev, O and Mégraud, F and Kump, PK and Nakov, R and Goldenberg, SD and Satokari, R and Tkatch, S and Sanguinetti, M and Cammarota, G and Dorofeev, A and Gubska, O and Ianiro, G and Mattila, E and Arasaradnam, RP and Sarin, SK and Sood, A and Putignani, L and Alric, L and Baunwall, SMD and Kupcinskas, J and Link, A and Goorhuis, AG and Verspaget, HW and Ponsioen, C and Hold, GL and Tilg, H and Kassam, Z and Kuijper, EJ and Gasbarrini, A and Mulder, CJJ and Williams, HRT and Vehreschild, MJGT}, title = {A standardised model for stool banking for faecal microbiota transplantation: a consensus report from a multidisciplinary UEG working group.}, journal = {United European gastroenterology journal}, volume = {9}, number = {2}, pages = {229-247}, pmid = {33151137}, issn = {2050-6414}, support = {PB-PG-0418-20007/DH_/Department of Health/United Kingdom ; }, mesh = {Age Factors ; Biological Specimen Banks/*organization &amp; administration/standards ; Clostridioides difficile ; Clostridium Infections/immunology/therapy ; Contraindications, Procedure ; Donor Selection ; *Fecal Microbiota Transplantation/adverse effects/methods ; *Feces ; Humans ; Immunocompromised Host ; Informed Consent ; Quality Assurance, Health Care ; Recurrence ; Specimen Handling ; }, abstract = {BACKGROUND: Faecal microbiota transplantation is an emerging therapeutic option, particularly for the treatment of recurrent Clostridioides difficile infection. Stool banks that organise recruitment and screening of faeces donors are being embedded within the regulatory frameworks described in the European Union Tissue and Cells Directive and the technical guide to the quality and safety of tissue and cells for human application, published by the European Council.<br><br>OBJECTIVE: Several European and international consensus statements concerning faecal microbiota transplantation have been issued. While these documents provide overall guidance, we aim to provide a detailed description of all processes that relate to the collection, handling and clinical application of human donor stool in this document.<br><br>METHODS: Collaborative subgroups of experts on stool banking drafted concepts for all domains pertaining to stool banking. During a working group meeting in the United European Gastroenterology Week 2019 in Barcelona, these concepts were discussed and finalised to be included in our overall guidance document about faecal microbiota transplantation.<br><br>RESULTS: A guidance document for all domains pertaining to stool banking was created. This document includes standard operating manuals for several processes involved with stool banking, such as handling of donor material, storage and donor screening.<br><br>CONCLUSION: The implementation of faecal microbiota transplantation by stool banks in concordance with our guidance document will enable quality assurance and guarantee the availability of donor faeces preparations for patients.}, }
@article {pmid33144313, year = {2020}, author = {Manus, MB and Kuthyar, S and Perroni-Marañón, AG and Núñez-de la Mora, A and Amato, KR}, title = {Infant Skin Bacterial Communities Vary by Skin Site and Infant Age across Populations in Mexico and the United States.}, journal = {mSystems}, volume = {5}, number = {6}, pages = {}, pmid = {33144313}, issn = {2379-5077}, abstract = {Daily practices put humans in close contact with the surrounding environment, and differences in these practices have an impact on human physiology, development, and health. There is mounting evidence that the microbiome represents an interface that mediates interactions between the human body and the environment. In particular, the skin microbiome serves as the primary interface with the external environment and aids in host immune function by contributing as the first line of defense against pathogens. Despite these important connections, we have only a basic understanding of how the skin microbiome is first established, or which environmental factors contribute to its development. To this end, this study compared the skin bacterial communities of infants (n = 47) living in four populations in Mexico and the United States that span the socioeconomic gradient, where we predicted that variation in physical and social environments would shape the infant skin microbiome. Results of 16S rRNA bacterial gene sequencing on 119 samples (armpit, hand, and forehead) showed that infant skin bacterial diversity and composition are shaped by population-level factors, including those related to socioeconomic status and household composition, and vary by skin site and infant age. Differences in infant-environment interactions, including with other people, appear to vary across the populations, likely influencing infant microbial exposures and, in turn, the composition of infant skin bacterial communities. These findings suggest that variation in microbial exposures stemming from the local environment in infancy can impact the establishment of the skin microbiome across body sites, with implications for developmental and health outcomes.IMPORTANCE This study contributes to the sparse literature on the infant skin microbiome in general, and the virtually nonexistent literature on the infant skin microbiome in a field setting. While microbiome research often addresses patterns at a national scale, this study addresses the influence of population-level factors, such as maternal socioeconomic status and contact with caregivers, on infant skin bacterial communities. This approach strengthens our understanding of how local variables influence the infant skin microbiome, and paves the way for additional studies to combine biological sample collection with questionnaires to adequately capture how specific behaviors dictate infant microbial exposures. Work in this realm has implications for infant care and health, as well as for investigating how the microbial communities of different body sites develop over time, with applications to specific health outcomes associated with the skin microbiome (e.g., immune system development or atopic dermatitis).}, }
@article {pmid33139482, year = {2021}, author = {North, OI and Davidson, AR}, title = {Phage Proteins Required for Tail Fiber Assembly Also Bind Specifically to the Surface of Host Bacterial Strains.}, journal = {Journal of bacteriology}, volume = {203}, number = {3}, pages = {}, pmid = {33139482}, issn = {1098-5530}, support = {FDN-15427//CIHR/Canada ; }, mesh = {Bacteria/genetics/*virology ; *Bacterial Physiological Phenomena ; Bacteriophages/genetics/*physiology ; Escherichia coli ; Gene Expression Regulation, Bacterial ; Host Specificity/*physiology ; Humans ; Lipopolysaccharides ; Protein Binding ; Viral Proteins/metabolism ; Virus Assembly ; Virus Attachment ; }, abstract = {To initiate their life cycle, phages must specifically bind to the surface of their bacterial hosts. Long-tailed phages often interact with the cell surface using fibers, which are elongated intertwined trimeric structures. The folding and assembly of these complex structures generally requires the activity of an intra- or intermolecular chaperone protein. Tail fiber assembly (Tfa) proteins are a very large family of proteins that serve as chaperones for fiber folding in a wide variety of phages that infect diverse species. A recent structural study showed that the Tfa protein from Escherichia coli phage Mu (TfaMu) mediates fiber folding and stays bound to the distal tip of the fiber, becoming a component of the mature phage particle. This finding revealed the potential for TfaMu to also play a role in cell surface binding. To address this issue, we have here shown that TfaMu binds to lipopolysaccharide (LPS), the cell surface receptor of phage Mu, with a similar strength as to the fiber itself. Furthermore, we have found that TfaMu and the Tfa protein from E. coli phage P2 bind LPS with distinct specificities that mirror the host specificity of these two phages. By comparing the sequences of these two proteins, which are 93% identical, we identified a single residue that is responsible for their distinct LPS-binding behaviors. Although we have not yet found conditions under which Tfa proteins influence host range, the potential for such a role is now evident, as we have demonstrated their ability to bind LPS in a strain-specific manner.IMPORTANCE With the growing interest in using phages to combat antibiotic-resistant infections or manipulate the human microbiome, establishing approaches for the modification of phage host range has become an important research topic. Tfa proteins are a large family of proteins known previously to function as chaperones for the folding of phage fibers, which are crucial determinants of host range for long-tailed phages. Here, we reveal that some Tfa proteins are bi-functional, with the additional activity of binding to LPS, the surface binding receptor for many phages. This discovery opens up new potential avenues for altering phage host range through engineering of the surface binding specificity of Tfa proteins.}, }
@article {pmid33134291, year = {2020}, author = {Rooney, CM and Mankia, K and Emery, P}, title = {The Role of the Microbiome in Driving RA-Related Autoimmunity.}, journal = {Frontiers in cell and developmental biology}, volume = {8}, number = {}, pages = {538130}, pmid = {33134291}, issn = {2296-634X}, support = {22294/VAC_/Versus Arthritis/United Kingdom ; }, abstract = {Once referred to as "normal commensal flora" the human microbiome plays an integral role between health and disease. The host mucosal surface replete with a multitude of immune cells is a vast arena constantly sensing and responding to antigen presentation and microbial by-products. It is this key role that may allow the microbiome to prime or protect the host from autoimmune disease. Rheumatoid arthritis (RA) is a chronic, disabling inflammatory condition characterized by a complex multifactorial etiology. The presence of certain genetic markers has been proven to increase susceptibility to RA however it does not guarantee disease development. Given low concordance rates demonstrated in monozygotic twin studies there is a clear implication for the involvement of external players in RA pathogenesis. Since the historical description of rheumatoid factor, numerous additional autoantibodies have been described in the sera of RA patients. The presence of anti-cyclic citrullinated protein antibody is now a standard test, and is associated with a more severe disease course. Interestingly these antibodies are detectable in patient's sera long before the clinical signs of RA occur. The production of autoantibodies is driven by the lack of tolerance of the immune system, and how tolerance is broken is a crucial question for understanding RA development. Here we review current literature on the role of the microbiome in RA development including periodontal, gut and lung mucosa, with particular focus on proposed mechanisms of host microbiome interactions. We discuss the use of Mendelian randomization to assign causality to the microbiome and present considerations for future studies.}, }
@article {pmid33131263, year = {2020}, author = {Merli, P and Putignani, L and Ruggeri, A and Del Chierico, F and Gargiullo, L and Galaverna, F and Gaspari, S and Pagliara, D and Russo, A and Pane, S and Strocchio, L and Algeri, M and Rea, F and Francesca Romeo, E and Bernaschi, P and Onetti Muda, A and Dallapiccola, B and Locatelli, F}, title = {Decolonization of multi-drug resistant bacteria by fecal microbiota transplantation in five pediatric patients before allogeneic hematopoietic stem cell transplantation: gut microbiota profiling, infectious and clinical outcomes.}, journal = {Haematologica}, volume = {105}, number = {11}, pages = {2686-2690}, pmid = {33131263}, issn = {1592-8721}, mesh = {Bacteria ; Child ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; *Hematopoietic Stem Cell Transplantation ; Humans ; *Pharmaceutical Preparations ; }, }
@article {pmid33125887, year = {2020}, author = {Spencer, SP and Sonnenburg, JL}, title = {When Gut Microbiota Creep into Fat, the Fat Creeps Back.}, journal = {Cell}, volume = {183}, number = {3}, pages = {589-591}, pmid = {33125887}, issn = {1097-4172}, support = {R01 DK085025/DK/NIDDK NIH HHS/United States ; T32 DK007056/DK/NIDDK NIH HHS/United States ; }, mesh = {Adaptation, Physiological ; Adipose Tissue ; *Crohn Disease ; *Gastrointestinal Microbiome ; Humans ; Mesentery ; }, abstract = {Ha and colleagues describe a previously unappreciated diversity of microbes in the mesenteric adipose tissue (MAT) surrounding the GI tract. Viable bacteria that are mislocalized from the gut microbiota and metabolically adapted to the MAT contribute to the "creeping fat" of Crohn's disease.}, }
@article {pmid33123104, year = {2020}, author = {Saladié, M and Caparrós-Martín, JA and Agudelo-Romero, P and Wark, PAB and Stick, SM and O'Gara, F}, title = {Microbiomic Analysis on Low Abundant Respiratory Biomass Samples; Improved Recovery of Microbial DNA From Bronchoalveolar Lavage Fluid.}, journal = {Frontiers in microbiology}, volume = {11}, number = {}, pages = {572504}, pmid = {33123104}, issn = {1664-302X}, abstract = {In recent years the study of the commensal microbiota is driving a remarkable paradigm shift in our understanding of human physiology. However, intrinsic technical difficulties associated with investigating the Microbiomics of some body niches are hampering the development of new knowledge. This is particularly the case when investigating the functional role played by the human microbiota in modulating the physiology of key organ systems. A major hurdle in investigating specific Microbiome communities is linked to low bacterial density and susceptibility to bias caused by environmental contamination. To prevent such inaccuracies due to background processing noise, harmonized tools for Microbiomic and bioinformatics practices have been recommended globally. The fact that the impact of this undesirable variability is negatively correlated with the DNA concentration in the sample highlights the necessity to improve existing DNA isolation protocols. In this report, we developed and tested a protocol to more efficiently recover bacterial DNA from low volumes of bronchoalveolar lavage fluid obtained from infants and adults. We have compared the efficiency of the described method with that of a commercially available kit for microbiome analysis in body fluids. We show that this new methodological approach performs better in terms of extraction efficiency. As opposed to commercial kits, the DNA extracts obtained with this new protocol were clearly distinguishable from the negative extraction controls in terms of 16S copy number and Microbiome community profiles. Altogether, we described a cost-efficient protocol that can facilitate microbiome research in low-biomass human niches.}, }
@article {pmid33120253, year = {2020}, author = {Chowdhury, S and Fong, SS}, title = {Leveraging genome-scale metabolic models for human health applications.}, journal = {Current opinion in biotechnology}, volume = {66}, number = {}, pages = {267-276}, doi = {10.1016/j.copbio.2020.08.017}, pmid = {33120253}, issn = {1879-0429}, mesh = {Genome ; Humans ; *Metabolic Networks and Pathways ; Models, Biological ; *Neoplasms/genetics ; }, abstract = {Genome-scale metabolic modeling is a scalable and extensible computational method for analyzing and predicting biological function. With the ongoing improvements in computational methods and experimental capabilities, genome-scale metabolic models (GEMs) are demonstrating utility in addressing human health applications. The initial areas of highest impact are likely to be health applications where disease states involve metabolic changes. In this review, we focus on recent application of GEMs to studying cancer and the human microbiome by describing the enabling methodologies and outcomes of these studies. We conclude with proposing some areas of research that are likely to arise as a result of recent methodological advances.}, }
@article {pmid33117737, year = {2020}, author = {Amado, PPP and Kawamoto, D and Albuquerque-Souza, E and Franco, DC and Saraiva, L and Casarin, RCV and Horliana, ACRT and Mayer, MPA}, title = {Oral and Fecal Microbiome in Molar-Incisor Pattern Periodontitis.}, journal = {Frontiers in cellular and infection microbiology}, volume = {10}, number = {}, pages = {583761}, pmid = {33117737}, issn = {2235-2988}, mesh = {Aggregatibacter actinomycetemcomitans ; Desulfovibrio ; Erysipelothrix ; Feces ; Humans ; Incisor ; *Microbiota ; Molar ; Peptostreptococcus ; *Periodontitis ; RNA, Ribosomal, 16S/genetics ; }, abstract = {In order to improve our understanding on the microbial complexity associated with Grade C/molar-incisor pattern periodontitis (GC/MIP), we surveyed the oral and fecal microbiomes of GC/MIP and compared to non-affected individuals (Control). Seven Afro-descendants with GC/MIP and seven age/race/gender-matched controls were evaluated. Biofilms from supra/subgingival sites (OB) and feces were collected and submitted to 16S rRNA sequencing. Aggregatibacter actinomycetemcomitans (Aa) JP2 clone genotyping and salivary nitrite levels were determined. Supragingival biofilm of GC/MIP presented greater abundance of opportunistic bacteria. Selenomonas was increased in subgingival healthy sites of GC/MIP compared to Control. Synergistetes and Spirochaetae were more abundant whereas Actinobacteria was reduced in OB of GC/MIP compared to controls. Aa abundance was 50 times higher in periodontal sites with PD≥ 4 mm of GC/MIP than in controls. GC/MIP oral microbiome was characterized by a reduction in commensals such as Kingella, Granulicatella, Haemophilus, Bergeyella, and Streptococcus and enrichment in periodontopathogens, especially Aa and sulfate reducing Deltaproteobacteria. The oral microbiome of the Aa JP2-like+ patient was phylogenetically distant from other GC/MIP individuals. GC/MIP presented a higher abundance of sulfidogenic bacteria in the feces, such as Desulfovibrio fairfieldensis, Erysipelothrix tonsillarum, and Peptostreptococcus anaerobius than controls. These preliminary data show that the dysbiosis of the microbiome in Afro-descendants with GC/MIP was not restricted to affected sites, but was also observed in supragingival and subgingival healthy sites, as well as in the feces. The understanding on differences of the microbiome between healthy and GC/MIP patients will help in developing strategies to improve and monitor periodontal treatment.}, }
@article {pmid33117362, year = {2020}, author = {Yegorov, S and Babenko, D and Kozhakhmetov, S and Akhmaltdinova, L and Kadyrova, I and Nurgozhina, A and Nurgaziyev, M and Good, SV and Hortelano, GH and Yermekbayeva, B and Kushugulova, A}, title = {Psoriasis Is Associated With Elevated Gut IL-1α and Intestinal Microbiome Alterations.}, journal = {Frontiers in immunology}, volume = {11}, number = {}, pages = {571319}, pmid = {33117362}, issn = {1664-3224}, mesh = {Adult ; Case-Control Studies ; Cohort Studies ; Cytokines/metabolism ; Dysbiosis/*immunology ; Female ; Gastrointestinal Microbiome/genetics/*immunology ; Humans ; Interleukin-1alpha/*metabolism ; Intestines/*immunology/microbiology ; Kazakhstan ; Male ; Middle Aged ; Psoriasis/*immunology ; RNA, Ribosomal, 16S/genetics ; Skin/*pathology ; }, abstract = {BACKGROUND: Psoriasis is a chronic inflammatory condition that predominantly affects the skin and is associated with extracutaneous disorders, such as inflammatory bowel disease and arthritis. Changes in gut immunology and microbiota are important drivers of proinflammatory disorders and could play a role in the pathogenesis of psoriasis. Therefore, we explored whether psoriasis in a Central Asian cohort is associated with alterations in select immunological markers and/or microbiota of the gut.<br><br>METHODS: We undertook a case-control study of stool samples collected from outpatients, aged 30-45 years, of a dermatology clinic in Kazakhstan presenting with plaque, guttate, or palmoplantar psoriasis (n = 20), and age-sex matched subjects without psoriasis (n = 20). Stool supernatant was subjected to multiplex ELISA to assess the concentration of 47 cytokines and immunoglobulins and to 16S rRNA gene sequencing to characterize microbial diversity in both psoriasis participants and controls.<br><br>RESULTS: The psoriasis group tended to have higher concentrations of most analytes in stool (29/47 = 61.7%) and gut IL-1&#x3b1; was significantly elevated (4.19-fold, p = 0.007) compared to controls. Levels of gut IL-1&#x3b1; in the psoriasis participants remained significantly unaltered up to 3 months after the first sampling (p = 0.430). Psoriasis was associated with alterations in gut Firmicutes, including elevated Faecalibacterium and decreased Oscillibacter and Roseburia abundance, but no association was observed between gut microbial diversity or Firmicutes/Bacteroidetes ratios and disease status.<br><br>CONCLUSIONS: Psoriasis may be associated with gut inflammation and dysbiosis. Studies are warranted to explore the use of gut microbiome-focused therapies in the management of psoriasis in this under-studied population.}, }
@article {pmid33114761, year = {2020}, author = {Haange, SB and Groeger, N and Froment, J and Rausch, T and Burkhardt, W and Gonnermann, S and Braune, A and Blaut, M and von Bergen, M and Rolle-Kampczyk, U}, title = {Multiplexed Quantitative Assessment of the Fate of Taurine and Sulfoquinovose in the Intestinal Microbiome.}, journal = {Metabolites}, volume = {10}, number = {11}, pages = {}, pmid = {33114761}, issn = {2218-1989}, support = {BR 2269/5-1//Deutsche Forschungsgemeinschaft/ ; BL 257/13-1//Deutsche Forschungsgemeinschaft/ ; }, abstract = {(1) Introduction: Sulfonates, which can be diet- or host-derived, are a class of compounds detected in the gut, are involved in host-microbiome interactions and have several health effects. Our aim was to develop a method to quantify five of the sulfonates in the intestine and apply it in a simplified human microbiome model. These were taurine, its metabolic precursor cysteate and one of its degradation products isethionate, as well as sulfoquinovose and one of its most relevant degradation products 2,3-dihydroxy-1-propanesulfonate. (2) Methods: An extraction and sample preparation method was developed, without the need for derivatization. To detect and quantify the extracted sulfonates, a multiplexed LC-MS/MS-MRM method was established. (3) Results: The accuracy and precision of the method were within GLP-accepted parameters (www.ema.europa.eu). To apply this method in a pilot study, we spiked either taurine or sulfoquinovose into an in vitro simplified human microbiota model with and without Bilophila wadsworthia, a known sulfonate utilizer. The results revealed that only the culture with B. wadsworthia was able to degrade taurine, with isethionate as an intermediate. After spiking the communities with sulfoquinovose, the results revealed that the simplified human microbiome model was able to degrade sulfoquinovose to 2,3-dihydroxypropane-1-sulfonate, which was probably catalyzed by Escherichia coli. In the community with B. wadsworthia, the 2,3-dihydroxypropane-1-sulfonate produced was further degraded by B. wadsworthia to sulfide. (4) Conclusions: We successfully developed a method for sulfonate quantification and applied it in a first pilot study.}, }
@article {pmid33113343, year = {2020}, author = {Hayes, W and Sahu, S}, title = {The Human Microbiome: History and Future.}, journal = {Journal of pharmacy &amp; pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques}, volume = {23}, number = {}, pages = {404-411}, doi = {10.18433/jpps31525}, pmid = {33113343}, issn = {1482-1826}, mesh = {Animals ; Biomedical Technology/*trends ; Humans ; Immune System/*microbiology ; Microbiota/*physiology ; Respiratory Tract Infections/epidemiology/microbiology ; }, abstract = {The microbiome plays an important role in human health and disease. Our current understanding of the human microbiome is limited. A significant amount of progress has been made in this area of research in the last two decades. The human microbiome plays an important role in host metabolism and physiology. Recent studies suggest a critical relationship between the human microbiome and host metabolism. The interactions between the microbiome and host metabolism affect human health and disease. However, this review of the literature indicates that more studies are required using new technologies to have a greater understanding of the role the human microbiome plays in human health and disease.}, }
@article {pmid33109750, year = {2020}, author = {Brinkac, LM and Rahman, N and Chua, LL and Thomas, S}, title = {Biomimetic Gut Model Systems for Development of Targeted Microbial Solutions for Enhancing Warfighter Health and Performance.}, journal = {mSystems}, volume = {5}, number = {5}, pages = {}, pmid = {33109750}, issn = {2379-5077}, abstract = {The human gut microbiome plays a vital role in both health and disease states and as a mediator of cognitive and physical performance. Despite major advances in our understanding of the role of gut microbes in host physiology, mechanisms underlying human-microbiome dynamics have yet to be fully elucidated. This knowledge gap represents a major hurdle to the development of targeted gut microbiome solutions influencing human health and performance outcomes. The microbiome as it relates to warfighter health and performance is of interest to the Department of Defense (DoD) with the development of interventions impacting gut microbiome resiliency among its top research priorities. While technological advancements are enabling the development of experimental model systems that facilitate mechanistic insights underpinning human health, disease, and performance, translatability to human outcomes is still questionable. This review discusses some of the drivers influencing the DoD's interest in the warfighter gut microbiome and describes current in vitro gut model systems supporting direct microbial-host interactions.}, }
@article {pmid33099885, year = {2021}, author = {Marco, ML}, title = {Defining how microorganisms benefit human health.}, journal = {Microbial biotechnology}, volume = {14}, number = {1}, pages = {35-40}, pmid = {33099885}, issn = {1751-7915}, mesh = {*Gastrointestinal Microbiome ; Humans ; *Microbiota ; *Probiotics ; }, abstract = {An appreciation for how microorganisms can benefit human health has grown over the past century. The future of this research will be to identify the specific microbial enzymatic pathways and molecules necessary for health promotion. Some of these 'beneficial factors' are already known for probiotics and species in the human microbiome, however, precise descriptions of the mechanistic details for their effects remain to be discovered. The need for this research is elevated by the potential use of microorganisms for preventing and treating the non-communicable diseases which are now the leading causes of death worldwide.}, }
@article {pmid33096717, year = {2020}, author = {Kiljunen, S}, title = {Editorial for the Special Issue: "Phage Therapy: A Biological Approach to Treatment of Bacterial Infections".}, journal = {Antibiotics (Basel, Switzerland)}, volume = {9}, number = {10}, pages = {}, pmid = {33096717}, issn = {2079-6382}, abstract = {The emergence of antibiotic-resistant bacteria presents a major challenge in terms of increased morbidity, mortality, and healthcare costs [...].}, }
@article {pmid33092203, year = {2020}, author = {Yang, D and Xu, W}, title = {Clustering on Human Microbiome Sequencing Data: A Distance-Based Unsupervised Learning Model.}, journal = {Microorganisms}, volume = {8}, number = {10}, pages = {}, pmid = {33092203}, issn = {2076-2607}, support = {145546/CAPMC/CIHR/Canada ; RGPIN20170667//Natural Sciences and Engineering Research Council of Canada/ ; CCCGEMIII//Crohn's and Colitis Canada/ ; 2019-2022//Edwin S.H. Leong Scholarship/ ; }, abstract = {Modeling and analyzing human microbiome allows the assessment of the microbial community and its impacts on human health. Microbiome composition can be quantified using 16S rRNA technology into sequencing data, which are usually skewed and heavy-tailed with excess zeros. Clustering methods are useful in personalized medicine by identifying subgroups for patients stratification. However, there is currently a lack of standardized clustering method for the complex microbiome sequencing data. We propose a clustering algorithm with a specific beta diversity measure that can address the presence-absence bias encountered for sparse count data and effectively measure the sample distances for sample stratification. Our distance measure used for clustering is derived from a parametric based mixture model producing sample-specific distributions conditional on the observed operational taxonomic unit (OTU) counts and estimated mixture weights. The method can provide accurate estimates of the true zero proportions and thus construct a precise beta diversity measure. Extensive simulation studies have been conducted and suggest that the proposed method achieves substantial clustering improvement compared with some widely used distance measures when a large proportion of zeros is presented. The proposed algorithm was implemented to a human gut microbiome study on Parkinson's diseases to identify distinct microbiome states with biological interpretations.}, }
@article {pmid33085540, year = {2020}, author = {Del Chierico, F and Grassini, P and Quagliariello, A and Torti, M and Russo, A and Reddel, S and Stocchi, F}, title = {The impact of intestinal microbiota on weight loss in Parkinson's disease patients: a pilot study.}, journal = {Future microbiology}, volume = {15}, number = {}, pages = {1393-1404}, doi = {10.2217/fmb-2019-0336}, pmid = {33085540}, issn = {1746-0921}, mesh = {Aged ; Bacteria/classification/genetics/isolation &amp; purification/metabolism ; Case-Control Studies ; Female ; *Gastrointestinal Microbiome ; Humans ; Inflammation ; Male ; Metabolic Networks and Pathways ; Middle Aged ; Parkinson Disease/diagnosis/microbiology/*pathology ; Pilot Projects ; RNA, Ribosomal, 16S/genetics ; *Weight Loss ; }, abstract = {Background: There is increasing evidence of the association between microbiome dysfunction and Parkinson's disease (PD). Moreover, some PD patients suffer from unintentional weight loss (WL) which may precede the motor manifestations of the disease. Materials &amp; methods: Gut microbiota profiling by 16S rRNA gene sequencing was performed in PD patients with an unintended WL, in steady weight patients (non-WL [NWL]) and in matched normal subjects. KEGG functional predictions were carried out. Results: Microbiota profiles revealed a dissimilarity between WL and NWL. Moreover, WL pathways were characterized by fatty acid biosynthesis, while NWL by inflammation pathways. Conclusion: The gut microbiota could participate in weight alteration observed in PD by the presence of bacteria involved in weight gain and inflammation, or conversely by bacteria implicated in energy expenditure.}, }
@article {pmid33085024, year = {2020}, author = {Deschamps, C and Fournier, E and Uriot, O and Lajoie, F and Verdier, C and Comtet-Marre, S and Thomas, M and Kapel, N and Cherbuy, C and Alric, M and Almeida, M and Etienne-Mesmin, L and Blanquet-Diot, S}, title = {Comparative methods for fecal sample storage to preserve gut microbial structure and function in an in vitro model of the human colon.}, journal = {Applied microbiology and biotechnology}, volume = {104}, number = {23}, pages = {10233-10247}, pmid = {33085024}, issn = {1432-0614}, mesh = {Colon ; Feces ; *Gastrointestinal Microbiome ; Humans ; RNA, Ribosomal, 16S/genetics ; Specimen Handling ; }, abstract = {In vitro gut models, such as the mucosal artificial colon (M-ARCOL), provide timely and cost-efficient alternatives to in vivo assays allowing mechanistic studies to better understand the role of human microbiome in health and disease. Using such models inoculated with human fecal samples may require a critical step of stool storage. The effects of preservation methods on microbial structure and function in in vitro gut models have been poorly investigated. This study aimed to assess the impact of three commonly used preserving methods, compared with fresh fecal samples used as a control, on the kinetics of lumen and mucus-associated microbiota colonization in the M-ARCOL model. Feces from two healthy donors were frozen 48 h at - 80 °C with or without cryoprotectant (10% glycerol) or lyophilized with maltodextrin and trehalose prior to inoculation of four parallel bioreactors (e.g., fresh stool, raw stool stored at - 80 °C, stool stored at - 80 °C with glycerol and lyophilized stool). Microbiota composition and diversity (qPCR and 16S metabarcoding) as well as metabolic activity (gases and short chain fatty acids) were monitored throughout the fermentation process (9 days). All the preservative treatments allowed the maintaining inside the M-ARCOL of a complex and functional microbiota, but considering stabilization time of microbial profiles and activities (and not technical constraints associated with the supply of frozen material), our results highlighted 48 h freezing at - 80 °C without cryoprotectant as the most efficient method. These results will help scientists to determine the most accurate method for fecal storage prior to inoculation of in vitro gut microbiome models. KEY POINTS: • In vitro ARCOL model reproduces luminal and mucosal human microbiome. • Short-term storage of fecal sample influences microbial stabilization and activity. • 48 h freezing at - 80°C: most efficient method to preserve microbial ecosystem. • Scientific and technical requirements: influencers of preservation method.}, }
@article {pmid33077849, year = {2020}, author = {Sternes, PR and Martin, TM and Paley, M and Diamond, S and Asquith, MJ and Brown, MA and Rosenbaum, JT}, title = {HLA-A alleles including HLA-A29 affect the composition of the gut microbiome: a potential clue to the pathogenesis of birdshot retinochoroidopathy.}, journal = {Scientific reports}, volume = {10}, number = {1}, pages = {17636}, pmid = {33077849}, issn = {2045-2322}, support = {R01 EY029266/EY/NEI NIH HHS/United States ; EY029266/NH/NIH HHS/United States ; }, mesh = {Adult ; Aged ; *Alleles ; Birdshot Chorioretinopathy/*genetics/microbiology ; Female ; Gastrointestinal Microbiome/*genetics ; HLA-A Antigens/*genetics ; Humans ; Male ; *Metagenome ; Middle Aged ; Whole Genome Sequencing ; }, abstract = {Birdshot retinochoroidopathy occurs exclusively in individuals who are HLA-A29 positive. The mechanism to account for this association is unknown. The gut microbiome has been causally implicated in many immune-mediated diseases. We hypothesized that HLA-A29 would affect the composition of the gut microbiome, leading to a dysbiosis and immune-mediated eye disease. Fecal and intestinal biopsy samples were obtained from 107 healthy individuals from Portland, Oregon environs, 10 of whom were HLA-A29 positive, undergoing routine colonoscopy. Bacterial profiling was achieved via 16S rRNA metabarcoding. Publicly available whole meta-genome sequencing data from the Human Microbiome Project (HMP), consisting of 298 healthy controls mostly of US origin, were also interrogated. PERMANOVA and sparse partial least squares discriminant analysis (sPLSDA) demonstrated that subjects who were HLA-A29 positive differed in bacterial species composition (beta diversity) compared to HLA-A29 negative subjects in both the Portland (p = 0.019) and HMP cohorts (p = 0.0002). The Portland and HMP cohorts evidenced different subsets of bacterial species associated with HLA-A29 status, likely due to differences in the metagenomic techniques employed. The functional composition of the HMP cohort did not differ overall (p = 0.14) between HLA-A29 positive and negative subjects, although some distinct pathways such as heparan sulfate biosynthesis showed differences. As we and others have shown for various HLA alleles, the HLA allotype impacts the composition of the microbiome. We hypothesize that HLA-A29 may predispose chorioretinitis via an altered gut microbiome.}, }
@article {pmid33075154, year = {2021}, author = {Wenger, K and Pendleton, C and Xie, XJ and Caplan, DJ and Drake, D and Marchini, L}, title = {Factors associated with the counts of selected oral microorganisms in nursing home residents.}, journal = {Special care in dentistry : official publication of the American Association of Hospital Dentists, the Academy of Dentistry for the Handicapped, and the American Society for Geriatric Dentistry}, volume = {41}, number = {1}, pages = {32-40}, doi = {10.1111/scd.12530}, pmid = {33075154}, issn = {1754-4505}, support = {/TR/NCATS NIH HHS/United States ; #U54TR001356/NH/NIH HHS/United States ; //Delta Dental of Iowa Foundation/ ; }, mesh = {Humans ; *Mouth, Edentulous ; Nursing Homes ; Oral Hygiene ; *Tooth ; }, abstract = {PURPOSE/AIM: To analyze potential factors associated with levels of selected oral pathogens, as well as total aerobic bacterial species, among nursing home residents.<br><br>MATERIALS AND METHODS: Nursing home residents were divided into three groups (G1 included people with teeth but no dentures, G2 included people with teeth and dentures, and G3 included people with no teeth and with dentures). All participants had microbiological samples collected from their oral cavity and dentures. Counts of total aerobic bacterial species, Porphyromonas gingivalis, Fusobacterium nucleatum, Actinomyces viscosus, Aggregatibacter actinomycetemcomitans, and Candida albicans were compared among groups using the Wilcoxon rank sum test. A multivariate analysis was also performed to control other available covariates.<br><br>RESULTS: Bivariate analysis revealed significant differences among the groups, and multivariate analysis showed that sex, the presence of natural teeth, denture wearing, oral hygiene indices, and systemic health conditions were associated with bacterial and Candida albicans log counts.<br><br>CONCLUSIONS: Presence of natural teeth and denture wearing, as well as oral hygiene, sex and systemic health conditions were associated with bacterial and Candida albicans log counts among nursing home residents.}, }
@article {pmid33073043, year = {2020}, author = {De Souza, ALPB}, title = {Finding the hot spot: identifying immune sensitive gastrointestinal tumors.}, journal = {Translational gastroenterology and hepatology}, volume = {5}, number = {}, pages = {48}, pmid = {33073043}, issn = {2415-1289}, abstract = {Although researchers have been trying to harness the immune system for over 100 years, the advent of immune checkpoint blockers (ICB) marks an era of significant clinical outcomes in various metastatic solid tumors, characterized by complete and durable responses. ICBs are monoclonal antibodies that target either of a pair of transmembrane molecules in tumors or T-cells involved in immune evasion. Currently 2 ICBs targeting the checkpoint program death 1 (PD-1), nivolumab and pembrolizumab, and one cytotoxic lymphocyte antigen-4 (CTLA-4) inhibitor (ipilimumab) are approved in gastrointestinal malignancies. We review herein the current evidence on predictive biomarkers for ICB response in gastrointestinal tumors. A review of literature based on the National Cancer Institute list of FDA-approved drugs for neoplasms and FDA-approved therapies at the FDA website was performed. An initial literature review was based on the American Association for Clinical Research meeting 2019, the American Society of Clinical Oncology meeting 2019 and the European Society of Medical Oncology 2019 proceedings. A systematic search of PubMed was performed involving MeSH browser terms such as biomarkers, immunotherapy, gastrointestinal diseases and neoplasms. When appropriate, American and British terms were used in the search. The most relevant predictor of response to ICBs is microsatellite instability (MSI) and the data is strongest for colorectal cancer. At least 3 prospective trials show evidence of PD-L1 as a predictive biomarker for ICB response in gastroesophageal malignancies. At least one prospective trial has described tumor mutational burden high (TMB-H), independent of MSI, as predictive of response in anal and biliary tract carcinomas. DNA Polymerase Epsilon (POLE) or delta (POL-D) mutations have been implicated in a subset of MSS colorectal cancer with TMB-H but this biomarker requires prospective validation. There is evolving data based on retrospective observations that gene alterations predicting acquired resistance and hyper-progression. Ongoing clinical research is assessing the role of the human microbiome and RNA-editing complex mutations as predictive biomarkers of response to ICBs. MSI has the strongest predictive power among current biomarkers for ICB response in gastrointestinal cancers. Data continue to accumulate from ongoing clinical trials and new biomarkers are emerging from pre-clinical studies, suggesting that drug combinations targeting pathways complimentary to the PD-1/PD-L1 axis inhibition will define a robust field of clinical research.}, }
@article {pmid33072872, year = {2020}, author = {Flores Bueso, Y and Walker, SP and Tangney, M}, title = {Characterization of FFPE-induced bacterial DNA damage and development of a repair method.}, journal = {Biology methods &amp; protocols}, volume = {5}, number = {1}, pages = {bpaa015}, pmid = {33072872}, issn = {2396-8923}, abstract = {Formalin-fixed, paraffin-embedded (FFPE) specimens have huge potential as source material in the field of human microbiome research. However, the effects of FFPE processing on bacterial DNA remain uncharacterized. Any effects are relevant for microbiome studies, where DNA template is often minimal and sequences studied are not limited to one genome. As such, we aimed to both characterize this FFPE-induced bacterial DNA damage and develop strategies to reduce and repair this damage. Our analyses indicate that bacterial FFPE DNA is highly fragmented, a poor template for PCR, crosslinked and bears sequence artefacts derived predominantly from oxidative DNA damage. Two strategies to reduce this damage were devised - an optimized decrosslinking procedure reducing sequence artefacts generated by high-temperature incubation, and secondly, an in vitro reconstitution of the base excision repair pathway. As evidenced by whole genome sequencing, treatment with these strategies significantly increased fragment length, reduced the appearance of sequence artefacts and improved the sequencing readability of bacterial and mammalian FFPE DNA. This study provides a new understanding of the condition of bacterial DNA in FFPE specimens and how this impacts downstream analyses, in addition to a strategy to improve the sequencing quality of bacterial and possibly mammalian FFPE DNA.}, }
@article {pmid33072766, year = {2020}, author = {Kirichenko, TV and Markina, YV and Sukhorukov, VN and Khotina, VA and Wu, WK and Orekhov, AN}, title = {A Novel Insight at Atherogenesis: The Role of Microbiome.}, journal = {Frontiers in cell and developmental biology}, volume = {8}, number = {}, pages = {586189}, pmid = {33072766}, issn = {2296-634X}, abstract = {There is an important task of current medicine to identify mechanisms and new markers of subclinical atherosclerosis in order to develop early targets for the diagnosis and treatment of this disease, since it causes such widespread diseases as myocardial infarction, stroke, sudden death, and other common reasons of disability and mortality in developed countries. In recent years, studies of the human microbiome in different fields of medicine have become increasingly popular; there is evidence from numerous studies of the significant contribution of microbiome in different steps of atherogenesis. This review attempted to determine the current status of the databases PubMed and Scopus (until May, 2020) to highlight current ideas on the potential role of microbiome and its metabolites in atherosclerosis development, its mechanisms of action in lipids metabolism, endothelial dysfunction, inflammatory pathways, and mitochondrial dysfunction. Results of clinical studies elucidating the relationship of microbiome with subclinical atherosclerosis and cardiovascular disease considered in this article demonstrate strong association of microbiome composition and its metabolites with atherosclerosis and cardiovascular disease. Data on microbiome impact in atherogenesis open a wide perspective to develop new diagnostic and therapeutic approaches, but further comprehensive studies are necessary.}, }
@article {pmid33067429, year = {2020}, author = {Rackaityte, E and Lynch, SV}, title = {The human microbiome in the 21[st] century.}, journal = {Nature communications}, volume = {11}, number = {1}, pages = {5256}, pmid = {33067429}, issn = {2041-1723}, support = {F31 AI136336/AI/NIAID NIH HHS/United States ; UM1 AI114271/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Bacteria/classification/genetics/isolation &amp; purification/metabolism ; Biodiversity ; Humans ; Mice ; *Microbiota ; }, abstract = {The human body supports a thriving diversity of microbes which comprise a dynamic, ancillary, functional system that synergistically develops in lock-step with physiological development of its host. The human microbiome field has transitioned from cataloging this rich diversity to dissecting molecular mechanisms by which microbiomes influence human health. Early life microbiome development trains immune function. Thus, vertically, horizontally, and environmentally acquired microbes and their metabolites have the potential to shape developmental trajectories with life-long implications for health.}, }
@article {pmid33066814, year = {2020}, author = {Castañeda, S and Muñoz, M and Villamizar, X and Hernández, PC and Vásquez, LR and Tito, RY and Ramírez, JD}, title = {Microbiota characterization in Blastocystis-colonized and Blastocystis-free school-age children from Colombia.}, journal = {Parasites &amp; vectors}, volume = {13}, number = {1}, pages = {521}, pmid = {33066814}, issn = {1756-3305}, mesh = {Blastocystis/genetics/*isolation &amp; purification ; Blastocystis Infections/*epidemiology/parasitology ; Child, Preschool ; Colombia/epidemiology ; Feces/microbiology/parasitology ; Female ; Firmicutes/genetics/*isolation &amp; purification ; *Gastrointestinal Microbiome ; Humans ; Intestines/microbiology/parasitology ; Male ; }, abstract = {BACKGROUND: Blastocystis is a protist that lives in the intestinal tract of a variety of hosts, including humans. It is still unclear how Blastocystis causes disease, which presents an ongoing challenge for researchers. Despite the controversial findings on the association between Blastocystis and clinical digestive manifestations, there is currently no consensus as to whether this protozoan actually behaves as a pathogen in humans. Furthermore, the relationship between Blastocystis and the intestinal microbiota composition is not yet clear. For that reason, the aim of this study was to identify if colonization by Blastocystis is related to changes in the diversity and relative abundance of bacterial communities, compared with those of Blastocystis-free individuals in a group of Colombian children.<br><br>METHODS: We took stool samples from 57 school-aged children attending a daycare institution in Popay&#xe1;n (Southwest Colombia). Whole DNA was extracted and examined by 16S-rRNA amplicon-based sequencing. Blastocystis was detected by real time PCR and other intestinal parasites were detected by microscopy. We evaluated if Blastocystis was associated with host variables and the diversity and abundance of microbial communities.<br><br>RESULTS: The composition of the intestinal bacterial community was not significantly different between Blastocystis-free and Blastocystis-colonized children. Despite this, we observed a higher microbial richness in the intestines of children colonized by Blastocystis, which could, therefore, be considered a benefit to intestinal health. The phylum Firmicutes was the predominant taxonomic unit in both groups analyzed. In Blastocystis-free individuals, there was a higher proportion of Bacteroidetes; similarly, in children colonized by Blastocystis, there was a higher relative abundance of the phylum Proteobacteria; however, no statistically significant differences were found between the comparison groups.<br><br>CONCLUSIONS: The presence of Blastocystis showed a decrease in Bacteroides, and an increase in the relative abundance of the genus Faecalibacterium. It was also evident that the presence of Blastocystis was unrelated to dysbiosis at the intestinal level; on the contrary, its presence did not show statistically differences in the intestinal microbiota composition. Nevertheless, we believe that Blastocystis plays a role in the ecology of the intestinal microbiota through its interaction with other microbial components.}, }
@article {pmid33062112, year = {2020}, author = {Tan, HY and Toh, YC}, title = {What can microfluidics do for human microbiome research?.}, journal = {Biomicrofluidics}, volume = {14}, number = {5}, pages = {051303}, pmid = {33062112}, issn = {1932-1058}, abstract = {Dysregulation of the human microbiome has been linked to various disease states, which has galvanized the efforts to modulate human health through microbiomes. Currently, human microbiome research is going through several phases to identify the constituent components of the microbiome, associate microbiome changes with physiological and pathological states, understand causative relationships, and finally translate this knowledge into therapeutics and diagnostics. The convergence of microfluidic technologies with molecular and cell profiling, microbiology, and tissue engineering can potentially be applied to these different phases of microbiome research to overcome the existing challenges faced by conventional approaches. The goal of this paper is to discuss and highlight the opportunities of applying different microfluidic technologies to specific areas of microbiome research as well as unique challenges that microfluidics must overcome when working with microbiome-relevant biological materials, e.g., micro-organisms, host tissues, and fluids. We will discuss the applicability of integrated microfluidic systems for processing biological samples for genomic sequencing analyses. For functional analysis of the microbiota, we will cover state-of-the-art microfluidic devices for microbiota cultivation and functional measurements. Finally, we highlight the use of organs-on-chips to model various microbiome-host tissue interactions. We envision that microfluidic technologies may hold great promise in advancing the knowledge on the interplay between microbiome and human health, as well as its eventual translation into microbiome-based diagnostics and therapeutics.}, }
@article {pmid33054163, year = {2020}, author = {Eller, CH and Raines, RT}, title = {Antimicrobial Synergy of a Ribonuclease and a Peptide Secreted by Human Cells.}, journal = {ACS infectious diseases}, volume = {6}, number = {11}, pages = {3083-3088}, pmid = {33054163}, issn = {2373-8227}, support = {R01 CA073808/CA/NCI NIH HHS/United States ; S10 OD018202/OD/NIH HHS/United States ; }, mesh = {Anti-Bacterial Agents ; *Anti-Infective Agents ; *Antimicrobial Cationic Peptides/pharmacology ; Escherichia coli/genetics ; Humans ; Ribonucleases ; }, abstract = {LL-37 is a secretory peptide that has antimicrobial activity. Ribonuclease 1 (RNase 1) is a secretory enzyme that is not cytotoxic. We find that human LL-37 and human RNase 1 can act synergistically to kill Gram-negative bacterial cells. In the presence of nontoxic concentrations of LL-37, RNase 1 is toxic to Escherichia coli cells at picomolar levels. Using wild-type RNase 1 and an inactive variant labeled with a fluorophore, we observe the adherence of RNase 1 to E. coli cells and its cellular entry in the presence of LL-37. These data suggest a natural means of modulating the human microbiome via the cooperation of an endogenous peptide (37 residues) and small enzyme (128 residues).}, }
@article {pmid33052545, year = {2021}, author = {Haak, BW and Westendorp, WF and van Engelen, TSR and Brands, X and Brouwer, MC and Vermeij, JD and Hugenholtz, F and Verhoeven, A and Derks, RJ and Giera, M and Nederkoorn, PJ and de Vos, WM and van de Beek, D and Wiersinga, WJ}, title = {Disruptions of Anaerobic Gut Bacteria Are Associated with Stroke and Post-stroke Infection: a Prospective Case-Control Study.}, journal = {Translational stroke research}, volume = {12}, number = {4}, pages = {581-592}, pmid = {33052545}, issn = {1868-601X}, support = {171002302//ZonMw (NL)/ ; 016116358//ZonMw (NL)/ ; 91716475//ZonMw (NL)/ ; 2009B095//Hartstichting (NL)/ ; ERC Starting Grant//H2020 European Research Council ()/ ; Spinoza Grant/ZONMW_/ZonMw/Netherlands ; }, mesh = {Aged ; Anaerobiosis ; Bacteria ; Case-Control Studies ; *Gastrointestinal Microbiome ; Humans ; RNA, Ribosomal, 16S/genetics ; }, abstract = {In recent years, preclinical studies have illustrated the potential role of intestinal bacterial composition in the risk of stroke and post-stroke infections. The results of these studies suggest that bacteria capable of producing volatile metabolites, including trimethylamine-N-oxide (TMAO) and butyrate, play opposing, yet important roles in the cascade of events leading to stroke. However, no large-scale studies have been undertaken to determine the abundance of these bacterial communities in stroke patients and to assess the impact of disrupted compositions of the intestinal microbiota on patient outcomes. In this prospective case-control study, rectal swabs from 349 ischemic and hemorrhagic stroke patients (median age, 71 years; IQR: 67-75) were collected within 24 h of hospital admission. Samples were subjected to 16S rRNA amplicon sequencing and subsequently compared with samples obtained from 51 outpatient age- and sex-matched controls (median age, 72 years; IQR, 62-80) with similar cardiovascular risk profiles but without active signs of stroke. Plasma protein biomarkers were analyzed using a combination of nuclear magnetic resonance (NMR) spectroscopy and liquid chromatography-mass spectrometry (LC-MS). Alpha and beta diversity analyses revealed higher disruption of intestinal communities during ischemic and hemorrhagic stroke compared with non-stroke matched control subjects. Additionally, we observed an enrichment of bacteria implicated in TMAO production and a loss of butyrate-producing bacteria. Stroke patients displayed two-fold lower plasma levels of TMAO than controls (median 1.97 vs 4.03 μM, Wilcoxon p < 0.0001). Finally, lower abundance of butyrate-producing bacteria within 24 h of hospital admission was an independent predictor of enhanced risk of post-stroke infection (odds ratio 0.77, p = 0.005), but not of mortality or functional patient outcome. In conclusion, aberrations in trimethylamine- and butyrate-producing gut bacteria are associated with stroke and stroke-associated infections.}, }
@article {pmid33047342, year = {2021}, author = {Reichhardt, MP and Messing, M and Andersson, S and Kolho, KL and Meri, S}, title = {Intestinal SALSA/dmbt1 levels are decreased in prematurely born infants.}, journal = {Scandinavian journal of immunology}, volume = {93}, number = {2}, pages = {e12987}, doi = {10.1111/sji.12987}, pmid = {33047342}, issn = {1365-3083}, support = {TYH2018313//Helsingin ja Uudenmaan Sairaanhoitopiiri/ ; TYH2019311//Helsingin ja Uudenmaan Sairaanhoitopiiri/ ; 292393//Academy of Finland/ ; //Sigrid Jus&#xe9;liuksen S&#xe4;&#xe4;ti&#xf6;/ ; //Pediatic Research Foundation/ ; }, mesh = {Calcium-Binding Proteins/*metabolism ; Complement C1q/metabolism ; DNA-Binding Proteins/*metabolism ; Feces ; Female ; Homeostasis/physiology ; Humans ; Immunoglobulin A/metabolism ; Infant, Newborn ; Infant, Premature/*metabolism ; Inflammation/metabolism ; Intestinal Mucosa/*metabolism ; Male ; Tumor Suppressor Proteins/*metabolism ; }, abstract = {The first months of life represent a crucial time period for an infant. Alongside establishing the early microbiome, the mucosal immunological homeostasis is being developed. Both processes may be perturbed in prematurely born infants. The glycoprotein SALSA plays a role in mucosal inflammation and microbial clearance. It is one of the most abundant molecules on the intestinal mucosal surfaces in early life. SALSA binds to many types of microbes and host defence molecules like IgA, C1q and collectin molecules. We here describe the development in faecal SALSA levels during the first three months of life. During these 90 days, the median SALSA level in full-term babies decreased from 1100 μg/mL (range 49-17 000 μg/mL) to 450 μg/mL (range 33-1000 μg/mL). Lower levels of SALSA were observed in prematurely born infants in the same time period. Our novel observation thus indicates an impact of prematurity on an important component of the infant intestinal immune system. Changes in SALSA in early life may have an effect on the early establishment of the human microbiome.}, }
@article {pmid33045987, year = {2020}, author = {Kenney, T and Gao, J and Gu, H}, title = {Application of OU processes to modelling temporal dynamics of the human microbiome, and calculating optimal sampling schemes.}, journal = {BMC bioinformatics}, volume = {21}, number = {1}, pages = {450}, pmid = {33045987}, issn = {1471-2105}, support = {RGPIN/4945-2014//Natural Sciences and Engineering Research Council of Canada/ ; RGPIN-2017-05108//Natural Sciences and Engineering Research Council of Canada/ ; }, mesh = {Healthy Volunteers ; Humans ; Kinetics ; *Microbiota ; *Models, Biological ; Stochastic Processes ; }, abstract = {BACKGROUND: The vast majority of microbiome research so far has focused on the structure of the microbiome at a single time-point. There have been several studies that measure the microbiome from a particular environment over time. A few models have been developed by extending time series models to accomodate specific features in microbiome data to address questions of stability and interactions of the microbime time series. Most research has observed the stability and mean reversion for some microbiomes. However, little has been done to study the mean reversion rates of these stable microbes and how sampling frequencies are related to such conclusions. In this paper, we begin to rectify this situation. We analyse two widely studied microbial time series data sets on four healthy individuals. We choose to study healthy individuals because we are interested in the baseline temporal dynamics of the microbiome.<br><br>RESULTS: For this analysis, we focus on the temporal dynamics of individual genera, absorbing all interactions in a stochastic term. We use a simple stochastic differential equation model to assess the following three questions. (1) Does the microbiome exhibit temporal continuity? (2) Does the microbiome have a stable state? (3) To better understand the temporal dynamics, how frequently should data be sampled in future studies? We find that a simple Ornstein-Uhlenbeck model which incorporates both temporal continuity and reversion to a stable state fits the data for almost every genus better than a Brownian motion model that contains only temporal continuity. The Ornstein-Uhlenbeck model also fits the data better than modelling separate time points as independent. Under the Ornstein-Uhlenbeck model, we calculate the variance of the estimated mean reversion rate (the speed with which each genus returns to its stable state). Based on this calculation, we are able to determine the optimal sample schemes for studying temporal dynamics.<br><br>CONCLUSIONS: There is evidence of temporal continuity for most genera; there is clear evidence of a stable state; and the optimal sampling frequency for studying temporal dynamics is in the range of one sample every 0.8-3.2 days.}, }
@article {pmid33042984, year = {2020}, author = {Gao, H and Sun, T and Yang, F and Yuan, J and Yang, M and Kang, W and Tang, D and Zhang, J and Feng, Q}, title = {The Pathogenic Effects of Fusobacterium nucleatum on the Proliferation, Osteogenic Differentiation, and Transcriptome of Osteoblasts.}, journal = {Frontiers in cell and developmental biology}, volume = {8}, number = {}, pages = {807}, pmid = {33042984}, issn = {2296-634X}, abstract = {As one of the most common oral diseases, periodontitis is closely correlated with tooth loss in middle-aged and elderly people. Fusobacterium nucleatum (F. nucleatum) contributes to periodontitis, but the evidence in alveolar bone loss is still unclear. In this study, cytological experiments and transcriptome analyses were performed to characterize the biological process abnormalities and the molecular changes of F. nucleatum-stimulated osteoblasts. F. nucleatum could inhibit cell proliferation, promote cell apoptosis, and elevate pro-inflammatory cytokine production of osteoblasts, and it also inhibited osteoblast differentiation and mineralized nodule formation and decreased the expression of osteogenetic genes and proteins. Whole-transcriptome analyses identified a total of 235 transcripts that were differentially expressed in all six time points, most of which were inflammation-related genes. The genes, Ccl2, Ccl20, Csf1, Cx3cl1, Cxcl1, Cxcl3, Il6, Birc3, Map3k8, Nos2, Nfkb2, Tnfrsf1b, and Vcam1, played core roles in a PPI network, and interacted closely with other ones in the infection. In addition, 133 osteogenesis-related differential expression genes (DEGs) were time-serially dynamically changed in a short time-series expression miner (STEM) analysis, which were enriched in multiple cancer-related pathways. The core dynamic DEGs (Mnda, Cyp1b1, Comp, Phex, Mmp3, Tnfrsf1b, Fbln5, and Nfkb2) had been reported to be closely related to the development and metastasis in tumor and cancer progress. This study is the first to evaluate the long-term interaction of F. nucleatum on osteoblasts, which might increase the risk of cell carcinogenesis of normal osteoblasts, and provides new insight into the pathogenesis of bacterial-induced bone destruction.}, }
@article {pmid33036309, year = {2020}, author = {Vernocchi, P and Marini, F and Capuani, G and Tomassini, A and Conta, G and Del Chierico, F and Malattia, C and De Benedetti, F and Martini, A and Dallapiccola, B and van Dijkhuizen, EHP and Miccheli, A and Putignani, L}, title = {Fused Omics Data Models Reveal Gut Microbiome Signatures Specific of Inactive Stage of Juvenile Idiopathic Arthritis in Pediatric Patients.}, journal = {Microorganisms}, volume = {8}, number = {10}, pages = {}, pmid = {33036309}, issn = {2076-2607}, abstract = {Juvenile idiopathic arthritis (JIA) is the most common rheumatic disease in children. Herein, we evaluated the relationship between the gut microbiome (GM) and disease phenotype by an integrated omics fused approach. In a multicenter, observational cohort study, stools from Italian JIA patients were collected at baseline, active, and inactive disease stages, and their GM compared to healthy controls (CTRLs). The microbiota metabolome was analyzed to detect volatile- and non-volatile organic compounds (VOCs); the data were fused with operational taxonomic units (OTUs) from 16S RNA targeted-metagenomics and classified by chemometric models. Non-VOCs did not characterize JIA patients nor JIA activity stages compared to CTRLs. The core of VOCs, (Ethanol, Methyl-isobutyl-ketone, 2,6-Dimethyl-4-heptanone and Phenol) characterized patients at baseline and inactive disease stages, while the OTUs represented by Ruminococcaceae, Lachnospiraceae and Clostridiacea discriminated between JIA inactive stage and CTRLs. No differences were highlighted amongst JIA activity stages. Finally, the fused data discriminated inactive and baseline stages versus CTRLs, based on the contribution of the invariant core of VOCs while Ruminococcaceae concurred for the inactive stage versus CTRLs comparison. In conclusion, the GM signatures enabled to distinguish the inactive disease stage from CTRLs.}, }
@article {pmid33031136, year = {2020}, author = {Shi, HL and Lan, YH and Hu, ZC and Yan, ZN and Liu, ZZ and Kadier, X and Ma, L and Yu, JY and Liu, J}, title = {Microecology research: a new target for the prevention of asthma.}, journal = {Chinese medical journal}, volume = {133}, number = {22}, pages = {2712-2720}, pmid = {33031136}, issn = {2542-5641}, mesh = {*Asthma/prevention &amp; control ; Child ; *Gastrointestinal Microbiome ; Humans ; *Hypersensitivity ; Intestines ; *Microbiota ; }, abstract = {The incidence and prevalence of asthma have increased remarkably in recent years. There are lots of factors contributing to the occurrence and development of asthma. With the improvement of sequencing technology, it has been found that the microbiome plays an important role in the formation of asthma in early life. The roles of the microbial environment and human microbiome in the occurrence and development of asthma have attracted more and more attention. The environmental microbiome influences the occurrence of asthma by shaping the human microbiome. The specific mechanism may be related to the immune regulation of Toll-like receptors and T cells (special Tregs). Intestinal microbiome is formed and changed by regulating diet and lifestyle in early life, which may affect the development and maturation of the pulmonary immune system through the intestinal-pulmonary axis. It is well-recognized that both environmental microbiomes and human microbiomes can influence the onset of asthma. This review aims to summarize the recent advances in the research of microbiome, its relationship with asthma, and the possible mechanism of the microbiome in the occurrence and development of asthma. The research of the microbial environment and human microbiome may provide a new target for the prevention of asthma in children who have high-risk factors to allergy. However, further study of "when and how" to regulate microbiome is still needed.}, }
@article {pmid33025908, year = {2020}, author = {Kozik, AJ}, title = {mSphere of Influence: Frameshift-a Vision for Human Microbiome Research.}, journal = {mSphere}, volume = {5}, number = {5}, pages = {}, pmid = {33025908}, issn = {2379-5042}, support = {F32 HL150954/HL/NHLBI NIH HHS/United States ; T32 HL007749/HL/NHLBI NIH HHS/United States ; }, mesh = {Female ; Humans ; *Microbiota ; }, abstract = {Ariangela J. Kozik studies the respiratory microbiome as it relates to asthma. In this mSphere of Influence article, she reflects on how two papers, "Time's up to adopt a biopsychosocial model to address racial and ethnic disparities in asthma outcomes" (E. C. Matsui, A. S. Adamson, and R. D. Peng, Allergy Clin Immunol 143:2024-2025, 2019, https://doi.org/10.1016/j.jaci.2019.03.015) and "Health disparities and the microbiome" (K. Findley, D. R. Williams, E. A. Grice, and V. L. Bonham, Trends Microbiol 24:847-850, 2016, https://doi.org/10.1016/j.tim.2016.08.001), shape her approach to human microbiome research.}, }
@article {pmid33019595, year = {2020}, author = {Santacroce, L and Charitos, IA and Ballini, A and Inchingolo, F and Luperto, P and De Nitto, E and Topi, S}, title = {The Human Respiratory System and its Microbiome at a Glimpse.}, journal = {Biology}, volume = {9}, number = {10}, pages = {}, pmid = {33019595}, issn = {2079-7737}, abstract = {The recent COVID-19 pandemic promoted efforts to better understand the organization of the respiratory microbiome and its evolution from birth to adulthood and how it interacts with external pathogens and the host immune system. This review aims to deepen understanding of the essential physiological functions of the resident microbiome of the respiratory system on human health and diseases. First, the general characteristics of the normal microbiota in the different anatomical sites of the airways have been reported in relation to some factors such as the effect of age, diet and others on its composition and stability. Second, we analyze in detail the functions and composition and the correct functionality of the microbiome in the light of current knowledge. Several studies suggest the importance of preserving the micro-ecosystem of commensal, symbiotic and pathogenic microbes of the respiratory system, and, more recently, its relationship with the intestinal microbiome, and how it also leads to the maintenance of human health, has become better understood.}, }
@article {pmid33014929, year = {2020}, author = {Durack, J and Christophersen, CT}, title = {Human Respiratory and Gut Microbiomes-Do They Really Contribute to Respiratory Health?.}, journal = {Frontiers in pediatrics}, volume = {8}, number = {}, pages = {528}, pmid = {33014929}, issn = {2296-2360}, abstract = {Human gastrointestinal and respiratory tracts are colonized by diverse polymicrobial communities shortly after birth, which are continuously molded by environmental exposure. The development of the resident microbiota in early life is a critical factor in the maturation of a healthy immune system. Disturbances to the intricate relationship between environmental exposure and maturation of the infant microbiome have been increasingly identified as a potential contributor to a range of childhood diseases. This review details recent evidence that implicates the contribution of gut and airway microbiome to pediatric respiratory health.}, }
@article {pmid33012230, year = {2020}, author = {Jacobson, DK and Honap, TP and Monroe, C and Lund, J and Houk, BA and Novotny, AC and Robin, C and Marini, E and Lewis, CM}, title = {Functional diversity of microbial ecologies estimated from ancient human coprolites and dental calculus.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {375}, number = {1812}, pages = {20190586}, pmid = {33012230}, issn = {1471-2970}, support = {R01 GM089886/GM/NIGMS NIH HHS/United States ; }, mesh = {Archaeology ; Bacteria/*isolation &amp; purification ; Belize ; DNA, Ancient/*analysis ; DNA, Bacterial/analysis ; Dental Calculus/*history/microbiology ; Feces/*microbiology ; High-Throughput Nucleotide Sequencing ; History, Ancient ; History, Medieval ; Humans ; Italy ; Mexico ; *Microbiota ; }, abstract = {Human microbiome studies are increasingly incorporating macroecological approaches, such as community assembly, network analysis and functional redundancy to more fully characterize the microbiome. Such analyses have not been applied to ancient human microbiomes, preventing insights into human microbiome evolution. We address this issue by analysing published ancient microbiome datasets: coprolites from Rio Zape (n = 7; 700 CE Mexico) and historic dental calculus (n = 44; 1770-1855 CE, UK), as well as two novel dental calculus datasets: Maya (n = 7; 170 BCE-885 CE, Belize) and Nuragic Sardinians (n = 11; 1400-850 BCE, Italy). Periodontitis-associated bacteria (Treponema denticola, Fusobacterium nucleatum and Eubacterium saphenum) were identified as keystone taxa in the dental calculus datasets. Coprolite keystone taxa included known short-chain fatty acid producers (Eubacterium biforme, Phascolarctobacterium succinatutens) and potentially disease-associated bacteria (Escherichia, Brachyspira). Overlap in ecological profiles between ancient and modern microbiomes was indicated by similarity in functional response diversity profiles between contemporary hunter-gatherers and ancient coprolites, as well as parallels between ancient Maya, historic UK, and modern Spanish dental calculus; however, the ancient Nuragic dental calculus shows a distinct ecological structure. We detected key ecological signatures from ancient microbiome data, paving the way to expand understanding of human microbiome evolution. This article is part of the theme issue 'Insights into health and disease from ancient biomolecules'.}, }
@article {pmid33012224, year = {2020}, author = {Schnorr, SL}, title = {The soil in our microbial DNA informs about environmental interfaces across host and subsistence modalities.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {375}, number = {1812}, pages = {20190577}, pmid = {33012224}, issn = {1471-2970}, mesh = {DNA, Bacterial/*analysis ; Humans ; *Microbiota ; *Soil Microbiology ; }, abstract = {In this study, I use microbiome datasets from global soil samples and diverse hosts to learn whether soil microbial taxa are found in host microbiomes, and whether these observations fit the narrative that environmental interaction influences human microbiomes. A major motivation for conducting host-associated microbiome research is to contribute towards understanding how the environment may influence host physiology. The microbial molecular network is considered a key vector by which environmental traits may be transmitted to the host. Research on human evolution seeks evidence that can inform about the living experiences of human ancestors. This objective is substantially enhanced by recent work on ancient biomolecules from preserved microbial tissues, such as dental calculus, faecal sediments and whole coprolites. A challenge yet is to distinguish authentic biomolecules from environmental contaminants deposited contemporaneously, primarily from soil. However, we do not have sound expectations about the soil microbial elements arriving to host-associated microbiomes in a modern context. One assumption in human microbiome research is that proximity to the natural environment should affect biodiversity or impart genetic elements. I present evidence supporting the assumption that environmental soil taxa are found among host-associated gut taxa, which can recapitulate the surrounding host habitat ecotype. Soil taxa found in gut microbiomes relate to a set of universal 'core' taxa for all soil ecotypes, demonstrating that widespread host organisms may experience a consistent pattern of external environmental cues, perhaps critical for development. Observed differentiation of soil feature diversity, abundance and composition among human communities, great apes and invertebrate hosts also indicates that lifestyle patterns are inferable from an environmental signal that is retrievable from gut microbiome amplicon data. This article is part of the theme issue 'Insights into health and disease from ancient biomolecules'.}, }
@article {pmid33007632, year = {2021}, author = {Wan, X and Hendrix, H and Skurnik, M and Lavigne, R}, title = {Phage-based target discovery and its exploitation towards novel antibacterial molecules.}, journal = {Current opinion in biotechnology}, volume = {68}, number = {}, pages = {1-7}, doi = {10.1016/j.copbio.2020.08.015}, pmid = {33007632}, issn = {1879-0429}, mesh = {Anti-Bacterial Agents ; Bacteria/genetics ; *Bacteriophages/genetics ; Biological Evolution ; *Phage Therapy ; }, abstract = {The deeply intertwined evolutionary history between bacteriophages and bacteria has endowed phages with highly specific mechanisms to hijack bacterial cell metabolism for their propagation. Here, we present a comprehensive, phage-driven strategy to reveal novel antibacterial targets by the exploitation of phage-bacteria interactions. This strategy will enable the design of small molecules, which mimic the inhibitory phage proteins, and allow the subsequent hit-to-lead development of these antimicrobial compounds. This proposed small molecule approach is distinct from phage therapy and phage enzyme-based antimicrobials and may produce a more sustainable generation of new antibiotics that exploit novel bacterial targets and act in a pathogen-specific manner.}, }
@article {pmid33007464, year = {2021}, author = {Bhar, S and Edelmann, MJ and Jones, MK}, title = {Characterization and proteomic analysis of outer membrane vesicles from a commensal microbe, Enterobacter cloacae.}, journal = {Journal of proteomics}, volume = {231}, number = {}, pages = {103994}, doi = {10.1016/j.jprot.2020.103994}, pmid = {33007464}, issn = {1876-7737}, support = {R21 AI140012/AI/NIAID NIH HHS/United States ; }, mesh = {Bacterial Outer Membrane Proteins ; *Enterobacter cloacae ; Gram-Negative Bacteria ; Humans ; Proteome ; *Proteomics ; Symbiosis ; }, abstract = {Outer membrane vesicles (OMVs) are membrane-enclosed spherical entities released by gram-negative bacteria and are important for bacterial survival under stress conditions. There have been numerous studies on OMVs released by gram-negative pathogenic bacteria, but an understanding of the functions and characteristics of the OMVs produced by commensal microbes is still lacking. Enterobacter cloacae is a gram-negative commensal bacterium present in the human gut microbiome, but this organism can also function as an opportunistic pathogen. Understanding the OMV-mediated communication route between bacteria-bacteria or bacteria-host is essential for the determination of the biological functions of the commensal bacterium in the gut and delineating between benign and virulent characteristics. In this study, we have described a proteome of E. cloacae OMVs, which are membrane vesicles in a size range of 20-300 nm. Proteomic analysis showed the presence of membrane-bound proteins, including transporters, receptors, signaling molecules, and protein channels. The physical and proteomic analyses also indicate this bacterium uses two mechanisms for OMV production. This study is one of the few existing descriptions of the proteomic profile of OMVs generated by a commensal Proteobacteria, and the first report of OMVs produced by E. cloacae. SIGNIFICANCE: This study prioritizes the importance of understanding the vesicular proteome of the human commensal bacterium, Enterobacter cloacae. We demonstrate for the first time that the gram-negative bacterium E. cloacae ATCC 13047 produces outer membrane vesicles (OMVs). The proteomic analysis showed enrichment of membrane-bound proteins in these vesicles. Understanding the cargo proteins of OMVs will help in exploring the physiological and functional role of these vesicles in the human microbiome and how they assist in the conversion of a bacterium from commensal to pathogen under certain conditions. While EM images reveal vesicles budding from the bacterial surface, the presence of cytoplasmic proteins and genomic DNA within the OMVs indicate that explosive cell lysis is an additional mechanism of biogenesis for these OMVs along with outer membrane blebbing. This research encourages future work on characterizing membrane vesicles produced by commensal bacterial and investigating their role in cell to cell communication.}, }
@article {pmid33007342, year = {2020}, author = {Rajeev, R and Prathiviraj, R and Kiran, GS and Selvin, J}, title = {Zoonotic evolution and implications of microbiome in viral transmission and infection.}, journal = {Virus research}, volume = {290}, number = {}, pages = {198175}, pmid = {33007342}, issn = {1872-7492}, mesh = {Animals ; *Biological Evolution ; COVID-19/transmission/virology ; Chiroptera/virology ; Coronaviridae/classification/*genetics/physiology ; Coronaviridae Infections/*transmission/virology ; Genome, Viral/genetics ; Humans ; *Microbiota ; Phylogeny ; SARS-CoV-2/classification/genetics/physiology ; Zoonoses/*transmission/virology ; }, abstract = {The outbreak and spread of new strains of coronavirus (SARS-CoV-2) remain a global threat with increasing cases in affected countries. The evolutionary tree of SARS-CoV-2 revealed that Porcine Reproductive and Respiratory Syndrome virus 2, which belongs to the Beta arterivirus genus from the Arteriviridae family is possibly the most ancient ancestral origin of SARS-CoV-2 and other Coronaviridae. This review focuses on phylogenomic distribution and evolutionary lineage of zoonotic viral cross-species transmission of the Coronaviridae family and the implications of bat microbiome in zoonotic viral transmission and infection. The review also casts light on the role of the human microbiome in predicting and controlling viral infections. The significance of microbiome-mediated interventions in the treatment of viral infections is also discussed. Finally, the importance of synthetic viruses in the study of viral evolution and transmission is highlighted.}, }
@article {pmid33007265, year = {2020}, author = {Korpela, K and Helve, O and Kolho, KL and Saisto, T and Skogberg, K and Dikareva, E and Stefanovic, V and Salonen, A and Andersson, S and de Vos, WM}, title = {Maternal Fecal Microbiota Transplantation in Cesarean-Born Infants Rapidly Restores Normal Gut Microbial Development: A Proof-of-Concept Study.}, journal = {Cell}, volume = {183}, number = {2}, pages = {324-334.e5}, doi = {10.1016/j.cell.2020.08.047}, pmid = {33007265}, issn = {1097-4172}, mesh = {Adult ; Cesarean Section/adverse effects ; Delivery, Obstetric ; Fecal Microbiota Transplantation/*methods ; Feces/*microbiology ; Female ; Gastrointestinal Microbiome/*physiology ; Humans ; Infant ; Infant, Newborn ; Male ; Microbiota/physiology ; Mothers ; Pregnancy ; Proof of Concept Study ; Vagina/microbiology ; }, abstract = {Infants born by vaginal delivery are colonized with maternal fecal microbes. Cesarean section (CS) birth disturbs mother-to-neonate transmission. In this study (NCT03568734), we evaluated whether disturbed intestinal microbiota development could be restored in term CS-born infants by postnatal, orally delivered fecal microbiota transplantation (FMT). We recruited 17 mothers, of whom seven were selected after careful screening. Their infants received a diluted fecal sample from their own mothers, taken 3 weeks prior to delivery. All seven infants had an uneventful clinical course during the 3-month follow-up and showed no adverse effects. The temporal development of the fecal microbiota composition of FMT-treated CS-born infants no longer resembled that of untreated CS-born infants but showed significant similarity to that of vaginally born infants. This proof-of-concept study demonstrates that the intestinal microbiota of CS-born infants can be restored postnatally by maternal FMT. However, this should only be done after careful clinical and microbiological screening.}, }
@article {pmid33001550, year = {2020}, author = {Shetty, SA and Boeren, S and Bui, TPN and Smidt, H and de Vos, WM}, title = {Unravelling lactate-acetate and sugar conversion into butyrate by intestinal Anaerobutyricum and Anaerostipes species by comparative proteogenomics.}, journal = {Environmental microbiology}, volume = {22}, number = {11}, pages = {4863-4875}, pmid = {33001550}, issn = {1462-2920}, support = {024.002.002//Nederlandse Organisatie voor Wetenschappelijk Onderzoek/ ; NRGWI.obrug.2018.005//Nederlandse Organisatie voor Wetenschappelijk Onderzoek/ ; }, mesh = {Acetates/*metabolism ; Bacterial Proteins/genetics/metabolism ; Butyrates/*metabolism ; Clostridiales/classification/genetics/*metabolism ; Fermentation ; Humans ; Intestines/*microbiology ; Lactic Acid/*metabolism ; Multigene Family ; Phylogeny ; Proteogenomics ; Sugars/*metabolism ; }, abstract = {The d- and l-forms of lactate are important fermentation metabolites produced by intestinal bacteria but are found to negatively affect mucosal barrier function and human health. Both enantiomers of lactate can be converted with acetate into the presumed beneficial butyrate by a phylogenetically related group of anaerobes, including Anaerobutyricum and Anaerostipes spp. This is a low energy yielding process with a partially unknown pathway in Anaerobutyricum and Anaerostipes spp. and hence, we sought to address this via a comparative genomics, proteomics and physiology approach. We compared growth of Anaerobutyricum soehngenii on lactate with that on sucrose and sorbitol. Comparative proteomics revealed complete pathway of butyrate formation from sucrose, sorbitol and lactate. Notably, a gene cluster, lctABCDEF was abundantly expressed when grown on lactate. This gene cluster encodes a lactate dehydrogenase (lctD), electron transport proteins A and B (lctCB), nickel-dependent racemase (lctE), lactate permease (lctF) and short-chain acyl-CoA dehydrogenase (lctG). Investigation of available genomes of intestinal bacteria revealed this new gene cluster to be highly conserved in only Anaerobutyricum and Anaerostipes spp. Present study demonstrates that A. soehngenii and several related Anaerobutyricum and Anaerostipes spp. are highly adapted for a lifestyle involving lactate plus acetate utilization in the human intestinal tract.}, }
@article {pmid33001460, year = {2021}, author = {Ottman, N and Barrientos-Somarribas, M and Fyhrquist, N and Alexander, H and Wisgrill, L and Olah, P and Tsoka, S and Greco, D and Levi-Schaffer, F and Soumelis, V and Schröder, JM and Kere, J and Nestle, FO and Barker, J and Ranki, A and Lauerma, A and Homey, B and Andersson, B and Alenius, H}, title = {Microbial and transcriptional differences elucidate atopic dermatitis heterogeneity across skin sites.}, journal = {Allergy}, volume = {76}, number = {4}, pages = {1173-1187}, pmid = {33001460}, issn = {1398-9995}, mesh = {*Dermatitis, Atopic/genetics ; *Eczema ; Humans ; *Microbiota ; Skin ; Staphylococcus aureus/genetics ; }, abstract = {It is well established that different sites in healthy human skin are colonized by distinct microbial communities due to different physiological conditions. However, few studies have explored microbial heterogeneity between skin sites in diseased skin, such as atopic dermatitis (AD) lesions. To address this issue, we carried out deep analysis of the microbiome and transcriptome in the skin of a large cohort of AD patients and healthy volunteers, comparing two physiologically different sites: upper back and posterior thigh. Microbiome samples and biopsies were obtained from both lesional and nonlesional skin to identify changes related to the disease process. Transcriptome analysis revealed distinct disease-related gene expression profiles depending on anatomical location, with keratinization dominating the transcriptomic signatures in posterior thigh, and lipid metabolism in the upper back. Moreover, we show that relative abundance of Staphylococcus aureus is associated with disease severity in the posterior thigh, but not in the upper back. Our results suggest that AD may select for similar microbes in different anatomical locations-an "AD-like microbiome," but distinct microbial dynamics can still be observed when comparing posterior thigh to upper back. This study highlights the importance of considering the variability across skin sites when studying the development of skin inflammation.}, }
@article {pmid32999084, year = {2020}, author = {Johnson, MDL}, title = {mSphere Highlights Black In Microbiology Week.}, journal = {mSphere}, volume = {5}, number = {5}, pages = {}, pmid = {32999084}, issn = {2379-5042}, mesh = {Betacoronavirus ; Black People/*genetics ; COVID-19 ; Coronavirus Infections/epidemiology ; *Genetic Determinism ; Humans ; Microbiology ; Microbiota ; Pandemics ; Pneumonia, Viral/epidemiology ; Racism/*prevention &amp; control ; SARS-CoV-2 ; }, abstract = {The inaugural Black In Microbiology Week (#BlackInMicro) is 28 September 2020 through 4 October 2020. Its mission is to "showcase the presence and accomplishments of Black microbiologists from around the globe, connect Black microbiologists with one another and foster a sense of community among them, and provide a forum for the discussion of racial disparities in microbiology and its subfields." Participation in this event will happen primarily over Twitter through the hashtag #BlackInMicro and over Zoom through registration on the website https://blackinmicrobiology.org/ An additional mission of Black In Microbiology Week is to amplify black scientists. Today, mSphere does this by presenting two mSphere of Influence commentaries from Black In Microbiology co-lead organizers Ariangela J. Kozik ("mSphere of Influence: frameshift-a vision for human microbiome research" [mSphere 5:e00944-20, 2020, https://doi.org/10.1128/mSphere.00944-20]) and Kishana Taylor ("mSphere of Influence: that's racist-COVID-19, biological determinism, and the limits of hypotheses" [mSphere 5:e00945-20, 2020, https://doi.org/10.1128/mSphere.00945-20]).}, }
@article {pmid32998695, year = {2020}, author = {Soverini, M and Rampelli, S and Turroni, S and Brigidi, P and Biagi, E and Candela, M}, title = {Do the human gut metagenomic species possess the minimal set of core functionalities necessary for life?.}, journal = {BMC genomics}, volume = {21}, number = {1}, pages = {678}, pmid = {32998695}, issn = {1471-2164}, mesh = {*Gastrointestinal Microbiome ; *Genes, Bacterial ; Genes, Essential ; Humans ; Intestinal Mucosa/metabolism/microbiology ; *Metagenome ; Metagenomics/methods/standards ; }, abstract = {BACKGROUND: Advances in bioinformatics recently allowed for the recovery of 'metagenomes assembled genomes' from human microbiome studies carried on with shotgun sequencing techniques. Such approach is used as a mean to discover new unclassified metagenomic species, putative biological entities having distinct metabolic traits.<br><br>RESULTS: In the present analysis we compare 400 genomes from isolates available on NCBI database and 10,000 human gut metagenomic species, screening all of them for the presence of a minimal set of core functionalities necessary, but not sufficient, for life. As a result, the metagenome-assembled genomes resulted systematically depleted in genes encoding for essential functions apparently needed to support autonomous bacterial life.<br><br>CONCLUSIONS: The relevant degree of lacking core functionalities that we observed in metagenome-assembled genomes raises some concerns about the effective completeness of metagenome-assembled genomes, suggesting caution in extrapolating biological information about their metabolic propensity and ecology in a complex environment like the human gastrointestinal tract.}, }
@article {pmid32995898, year = {2020}, author = {Lang, S and Brandau, S and Marchesi, JR and Jablonska, J and Thurnher, D and Mattheis, S and Buer, J and Hussain, T}, title = {[The microbiome in head and neck tumors-initial findings and outlook].}, journal = {HNO}, volume = {68}, number = {12}, pages = {905-910}, pmid = {32995898}, issn = {1433-0458}, mesh = {*Head and Neck Neoplasms ; Humans ; *Microbiota ; }, abstract = {Technical progress in molecular biology has allowed for a more detailed analysis of the composition of the human microbiome in recent years. Inter- and intraindividual differences in microbiome composition have been demonstrated, which in part correlate with the occurrence of certain diseases. For some of the so-called oncomicrobes, a direct relationship between their effect on the host organism and carcinogenesis has been demonstrated, predominantly for gastrointestinal cancers. Initial results for head and neck cancer show inter- and intraindividual differences in the local microbiota of the tumor environment, with certain bacterial strains over- or underrepresented. Our results confirm these findings, e.g., by showing a relative abundance of fusobacteria in tumor tissue while streptococci were relatively reduced. Currently available results show a high degree of inter- and intraindividual variation, thus requiring larger patient cohorts for functional analyses.}, }
@article {pmid32994293, year = {2020}, author = {Schmidt, V and Enav, H and Spector, TD and Youngblut, ND and Ley, RE}, title = {Strain-Level Analysis of Bifidobacterium spp. from Gut Microbiomes of Adults with Differing Lactase Persistence Genotypes.}, journal = {mSystems}, volume = {5}, number = {5}, pages = {}, pmid = {32994293}, issn = {2379-5077}, support = {/WT_/Wellcome Trust/United Kingdom ; R01 DK093595/DK/NIDDK NIH HHS/United States ; }, abstract = {One of the strongest associations between human genetics and the gut microbiome is a greater relative abundance of Bifidobacterium in adults with lactase gene (LCT) single nucleotide polymorphisms (SNPs) associated with lactase nonpersistence (GG genotypes), versus lactase persistence (AA/AG genotypes). To gain a finer-grained phylogenetic resolution of this association, we interrogated 1,680 16S rRNA libraries and 245 metagenomes from gut microbiomes of adults with various lactase persistence genotypes. We further employed a novel genome-capture-based enrichment of Bifidobacterium DNA from a subset of these metagenomes, including monozygotic (MZ) twin pairs, each sampled 2 or 3 times. B. adolescentis and B. longum were the most abundant Bifidobacterium species regardless of host LCT genotype. LCT genotypes could not be discriminated based on relative abundances of Bifidobacterium species or Bifidobacterium community structure. Three distinct metagenomic analysis methods of Bifidobacterium-enriched DNA revealed intraindividual temporal stability of B. longum, B. adolescentis, and B. bifidum strains against the background of a changeable microbiome. Two of our three methods also observed greater strain sharing within MZ twin pairs than within unrelated individuals for B. adolescentis, while no method revealed an effect of host LCT genotype on Bifidobacterium strain composition. Our results support a "rising tide lifts all boats" model for the dominant bifidobacteria in the adult gut: their higher abundance in lactase-nonpersistent than in lactase-persistent individuals results from an expansion at the genus level. Bifidobacterium species are known to be transmitted from mother to child and stable within individuals in infancy and childhood: our results extend this stability into adulthood.IMPORTANCE When humans domesticated animals, some adapted genetically to digest milk into adulthood (lactase persistence). The gut microbiomes of people with lactase-persistent genotypes (AA or AG) differ from those with lactase-nonpersistent genotypes (GG) by containing fewer bacteria belonging to the bifidobacteria, a group which contains beneficial species. Here, we asked if the gut microbiomes of adults with GG and AA/AG genotypes differ in the species of bifidobacteria present. In particular, we used a novel technique which allowed us to compare bifidobacteria in adults at the strain level, without the traditional need for culturing. Our results show that the GG genotype enhances the abundance of bifidobacteria regardless of species. We also noted that a person's specific strains are recoverable several years later, and twins can share the same ones. Given that bifidobacteria are inherited from mother to child, strain stability over time in adulthood suggests long-term, multigenerational inheritance.}, }
@article {pmid32993284, year = {2020}, author = {Ervin, SM and Simpson, JB and Gibbs, ME and Creekmore, BC and Lim, L and Walton, WG and Gharaibeh, RZ and Redinbo, MR}, title = {Structural Insights into Endobiotic Reactivation by Human Gut Microbiome-Encoded Sulfatases.}, journal = {Biochemistry}, volume = {59}, number = {40}, pages = {3939-3950}, doi = {10.1021/acs.biochem.0c00711}, pmid = {32993284}, issn = {1520-4995}, mesh = {Bacteria/chemistry/*enzymology/genetics/metabolism ; Catalytic Domain ; Feces/microbiology ; *Gastrointestinal Microbiome ; Genes, Bacterial ; Humans ; *Microbiota ; Models, Molecular ; Protein Conformation ; Sulfatases/chemistry/genetics/*metabolism ; }, abstract = {Phase II drug metabolism inactivates xenobiotics and endobiotics through the addition of either a glucuronic acid or sulfate moiety prior to excretion, often via the gastrointestinal tract. While the human gut microbial β-glucuronidase enzymes that reactivate glucuronide conjugates in the intestines are becoming well characterized and even controlled by targeted inhibitors, the sulfatases encoded by the human gut microbiome have not been comprehensively examined. Gut microbial sulfatases are poised to reactivate xenobiotics and endobiotics, which are then capable of undergoing enterohepatic recirculation or exerting local effects on the gut epithelium. Here, using protein structure-guided methods, we identify 728 distinct microbiome-encoded sulfatase proteins from the 4.8 million unique proteins present in the Human Microbiome Project Stool Sample database and 1766 gut microbial sulfatases from the 9.9 million sequences in the Integrated Gene Catalogue. We purify a representative set of these sulfatases, elucidate crystal structures, and pinpoint unique structural motifs essential to endobiotic sulfate processing. Gut microbial sulfatases differentially process sulfated forms of the neurotransmitters serotonin and dopamine, and the hormones melatonin, estrone, dehydroepiandrosterone, and thyroxine in a manner dependent both on variabilities in active site architecture and on markedly distinct oligomeric states. Taken together, these data provide initial insights into the structural and functional diversity of gut microbial sulfatases, providing a path toward defining the roles these enzymes play in health and disease.}, }
@article {pmid32993020, year = {2020}, author = {Ternák, G and Berényi, K and Sümegi, A and Szenczi, &#xc1; and Fodor, B and Németh, B and Kiss, I}, title = {Antibiotic Consumption Patterns in European Countries May Be Associated with the Incidence of Major Carcinomas.}, journal = {Antibiotics (Basel, Switzerland)}, volume = {9}, number = {10}, pages = {}, pmid = {32993020}, issn = {2079-6382}, abstract = {The possible role of the altered intestinal microbiome in the development of malignancies has been raised recently in several publications. Among external factors, antibiotics are considered to be the most important agent capable of producing dysbiosis in the gut flora, either temporally or permanently. The human microbiome has several beneficial effects in terms of maintaining appropriate human health, but its alteration has been implicated in the development of many illnesses. Our basic aim was to explore a possible relationship between the consumption of different antibiotic classes and the incidence of the most common cancer types (male, female) in European countries. A database of the average, yearly antibiotic consumption (1997-2018) has been developed and the consumption figures were compared to the eight, most frequent cancer incidence calculated for 2018 in 30 European countries. Pearson correlation has indicated different degrees of positive (supportive) and negative (inhibitor) significant associations between antibiotic consumption figures and cancer prevalence. It has been observed that certain antibiotic classes with positive correlation probably augment the incidence of certain cancer types, while others, with negative correlation, may show some inhibitory effect. The relatively higher or lower consumption pattern of different classes of antibiotics could be related to certain cancer prevalence figures in different European countries. Our results indicated that countries with relatively high consumption of narrow-spectrum penicillin (J01CE, J01CF) and tetracycline (J01A), like certain Scandinavian countries, showed a higher incidence of female colorectal cancer, female lung cancer, melanoma, breast, prostate and uterus corpus cancer. Countries with relatively higher consumption of broad-spectrum penicillin (J01CA, J01CR) and some broad-spectrum antibiotics (J01D, J01F, J01M), like Greece, Hungary, Slovakia, France, etc. showed a higher incidence rate of male lung cancer and male bladder cancer. The higher incidence rate of different cancer types showed association with the higher consumption of antibiotics with "augmenting" properties and with less consumption of antibiotics with "inhibitory" properties.}, }
@article {pmid32992653, year = {2020}, author = {Quagliariello, A and Del Chierico, F and Reddel, S and Russo, A and Onetti Muda, A and D'Argenio, P and Angelino, G and Romeo, EF and Dall'Oglio, L and De Angelis, P and Putignani, L and All The Other Fmt Opbg Committee Collaborators, }, title = {Fecal Microbiota Transplant in Two Ulcerative Colitis Pediatric Cases: Gut Microbiota and Clinical Course Correlations.}, journal = {Microorganisms}, volume = {8}, number = {10}, pages = {}, pmid = {32992653}, issn = {2076-2607}, support = {201702P003961//Ministero della Salute/ ; 201802G004314//MINISTERO DELLA SALUTE/ ; }, abstract = {Fecal microbiota transplantation (FMT) is a promising strategy in the management of inflammatory bowel disease (IBD). The clinical effects of this practice are still largely unknown and unpredictable. In this study, two children affected by mild and moderate ulcerative colitis (UC), were pre- and post-FMT monitored for clinical conditions and gut bacterial ecology. Microbiota profiling relied on receipts' time-point profiles, donors and control cohorts' baseline descriptions. After FMT, the improvement of clinical conditions was recorded for both patients. After 12 months, the mild UC patient was in clinical remission, while the moderate UC patient, after 12 weeks, had a clinical worsening. Ecological analyses highlighted an increase in microbiota richness and phylogenetic distance after FMT. This increase was mainly due to Collinsella aerofaciens and Eubacterium biforme, inherited by respective donors. Moreover, a decrease of Proteus and Blautia producta, and the increment of Parabacteroides, Mogibacteriaceae, Bacteroides eggerthi, Bacteroides plebeius, Ruminococcus bromii, and BBacteroidesovatus were associated with remission of the patient's condition. FMT results in a long-term response in mild UC, while in the moderate form there is probably need for multiple FMT administrations. FMT leads to a decrease in potential pathogens and an increase in microorganisms correlated to remission status.}, }
@article {pmid32991841, year = {2020}, author = {Ha, CWY and Martin, A and Sepich-Poore, GD and Shi, B and Wang, Y and Gouin, K and Humphrey, G and Sanders, K and Ratnayake, Y and Chan, KSL and Hendrick, G and Caldera, JR and Arias, C and Moskowitz, JE and Ho Sui, SJ and Yang, S and Underhill, D and Brady, MJ and Knott, S and Kaihara, K and Steinbaugh, MJ and Li, H and McGovern, DPB and Knight, R and Fleshner, P and Devkota, S}, title = {Translocation of Viable Gut Microbiota to Mesenteric Adipose Drives Formation of Creeping Fat in Humans.}, journal = {Cell}, volume = {183}, number = {3}, pages = {666-683.e17}, pmid = {32991841}, issn = {1097-4172}, support = {P30 DK042086/DK/NIDDK NIH HHS/United States ; U01 DK062413/DK/NIDDK NIH HHS/United States ; R01 DK123446/DK/NIDDK NIH HHS/United States ; F30 CA243480/CA/NCI NIH HHS/United States ; P01 DK046763/DK/NIDDK NIH HHS/United States ; P30 DK020595/DK/NIDDK NIH HHS/United States ; }, mesh = {Adipose Tissue/*microbiology/pathology ; Animals ; *Bacterial Translocation ; Biodiversity ; Biomarkers/metabolism ; Cell Polarity ; Cells, Cultured ; Colitis, Ulcerative/pathology ; Crohn Disease/microbiology/pathology ; *Gastrointestinal Microbiome/genetics ; Gene Expression Regulation ; Germ-Free Life ; Humans ; Ileum/microbiology/pathology ; Lipopolysaccharides/metabolism ; Macrophages/metabolism ; Mesentery/*microbiology ; Metagenome ; Metagenomics ; Mice ; Mice, Inbred C57BL ; Phenotype ; RNA, Ribosomal, 16S/genetics ; Stem Cells/metabolism ; }, abstract = {A mysterious feature of Crohn's disease (CD) is the extra-intestinal manifestation of "creeping fat" (CrF), defined as expansion of mesenteric adipose tissue around the inflamed and fibrotic intestine. In the current study, we explore whether microbial translocation in CD serves as a central cue for CrF development. We discovered a subset of mucosal-associated gut bacteria that consistently translocated and remained viable in CrF in CD ileal surgical resections, and identified Clostridium innocuum as a signature of this consortium with strain variation between mucosal and adipose isolates, suggesting preference for lipid-rich environments. Single-cell RNA sequencing characterized CrF as both pro-fibrotic and pro-adipogenic with a rich milieu of activated immune cells responding to microbial stimuli, which we confirm in gnotobiotic mice colonized with C. innocuum. Ex vivo validation of expression patterns suggests C. innocuum stimulates tissue remodeling via M2 macrophages, leading to an adipose tissue barrier that serves to prevent systemic dissemination of bacteria.}, }
@article {pmid32988391, year = {2020}, author = {Schwartz, DJ and Langdon, AE and Dantas, G}, title = {Understanding the impact of antibiotic perturbation on the human microbiome.}, journal = {Genome medicine}, volume = {12}, number = {1}, pages = {82}, pmid = {32988391}, issn = {1756-994X}, support = {R01 AT009741/AT/NCCIH NIH HHS/United States ; TL1 TR002344/TR/NCATS NIH HHS/United States ; 1U1CI000033 301/CC/CDC HHS/United States ; R01 AI123394/AI/NIAID NIH HHS/United States ; TL1 TR000449/TR/NCATS NIH HHS/United States ; R01 HD092414/HD/NICHD NIH HHS/United States ; AT009741/AT/NCCIH NIH HHS/United States ; TL1 TR000449/NH/NIH HHS/United States ; }, mesh = {Age Factors ; Anti-Bacterial Agents/*pharmacology ; Drug Resistance, Microbial ; Gastrointestinal Microbiome/drug effects ; Humans ; Microbiota/*drug effects ; }, abstract = {The human gut microbiome is a dynamic collection of bacteria, archaea, fungi, and viruses that performs essential functions for immune development, pathogen colonization resistance, and food metabolism. Perturbation of the gut microbiome's ecological balance, commonly by antibiotics, can cause and exacerbate diseases. To predict and successfully rescue such perturbations, first, we must understand the underlying taxonomic and functional dynamics of the microbiome as it changes throughout infancy, childhood, and adulthood. We offer an overview of the healthy gut bacterial architecture over these life stages and comment on vulnerability to short and long courses of antibiotics. Second, the resilience of the microbiome after antibiotic perturbation depends on key characteristics, such as the nature, timing, duration, and spectrum of a course of antibiotics, as well as microbiome modulatory factors such as age, travel, underlying illness, antibiotic resistance pattern, and diet. In this review, we discuss acute and chronic antibiotic perturbations to the microbiome and resistome in the context of microbiome stability and dynamics. We specifically discuss key taxonomic and resistance gene changes that accompany antibiotic treatment of neonates, children, and adults. Restoration of a healthy gut microbial ecosystem after routine antibiotics will require rationally managed exposure to specific antibiotics and microbes. To that end, we review the use of fecal microbiota transplantation and probiotics to direct recolonization of the gut ecosystem. We conclude with our perspectives on how best to assess, predict, and aid recovery of the microbiome after antibiotic perturbation.}, }
@article {pmid32984078, year = {2020}, author = {Marazzato, M and Zicari, AM and Aleandri, M and Conte, AL and Longhi, C and Vitanza, L and Bolognino, V and Zagaglia, C and De Castro, G and Brindisi, G and Schiavi, L and De Vittori, V and Reddel, S and Quagliariello, A and Del Chierico, F and Putignani, L and Duse, M and Palamara, AT and Conte, MP}, title = {16S Metagenomics Reveals Dysbiosis of Nasal Core Microbiota in Children With Chronic Nasal Inflammation: Role of Adenoid Hypertrophy and Allergic Rhinitis.}, journal = {Frontiers in cellular and infection microbiology}, volume = {10}, number = {}, pages = {458}, pmid = {32984078}, issn = {2235-2988}, mesh = {*Adenoids ; Child ; Dysbiosis ; Humans ; Hypertrophy ; Inflammation ; Metagenomics ; *Microbiota ; RNA, Ribosomal, 16S/genetics ; *Rhinitis, Allergic ; }, abstract = {Allergic rhinitis (AR) and adenoid hypertrophy (AH) are, in children, the main cause of partial or complete upper airway obstruction and reduction in airflow. However, limited data exist about the impact of the increased resistance to airflow, on the nasal microbial composition of children with AR end AH. Allergic rhinitis (AR) as well as adenoid hypertrophy (AH), represent extremely common pathologies in this population. Their known inflammatory obstruction is amplified when both pathologies coexist. In our study, the microbiota of anterior nares of 75 pediatric subjects with AR, AH or both conditions, was explored by 16S rRNA-based metagenomic approach. Our data show for the first time, that in children, the inflammatory state is associated to similar changes in the microbiota composition of AR and AH subjects respect to the healthy condition. Together with such alterations, we observed a reduced variability in the between-subject biodiversity on the other hand, these same alterations resulted amplified by the nasal obstruction that could constitute a secondary risk factor for dysbiosis. Significant differences in the relative abundance of specific microbial groups were found between diseased phenotypes and the controls. Most of these taxa belonged to a stable and quantitatively dominating component of the nasal microbiota and showed marked potentials in discriminating the controls from diseased subjects. A pauperization of the nasal microbial network was observed in diseased status in respect to the number of involved taxa and connectivity. Finally, while stable co-occurrence relationships were observed within both control- and diseases-associated microbial groups, only negative correlations were present between them, suggesting that microbial subgroups potentially act as maintainer of the eubiosis state in the nasal ecosystem. In the nasal ecosystem, inflammation-associated shifts seem to impact the more intimate component of the microbiota rather than representing the mere loss of microbial diversity. The discriminatory potential showed by differentially abundant taxa provide a starting point for future research with the potential to improve patient outcomes. Overall, our results underline the association of AH and AR with the impairment of the microbial interplay leading to unbalanced ecosystems.}, }
@article {pmid32981293, year = {2020}, author = {Son, JW and Shoaie, S and Lee, S}, title = {Systems Biology: A Multi-Omics Integration Approach to Metabolism and the Microbiome.}, journal = {Endocrinology and metabolism (Seoul, Korea)}, volume = {35}, number = {3}, pages = {507-514}, pmid = {32981293}, issn = {2093-5978}, support = {EP/S001301/1//Engineering and Physical Sciences Research Council/International ; //Biotechnology Biological Sciences Research Council/International ; BCMC19LH03//Institute of Clinical Medicine Research of Bucheon St. Mary's Hospital/International ; //Catholic Medical Center Research Foundation/International ; }, mesh = {Gastrointestinal Microbiome/*physiology ; Humans ; Liver Diseases/*microbiology/*physiopathology ; Metabolism ; Microbiota ; Pharmaceutical Preparations/metabolism ; *Systems Biology ; }, abstract = {The complex and dynamic nature of human physiology, as exemplified by metabolism, has often been overlooked due to the lack of quantitative and systems approaches. Recently, systems biology approaches have pushed the boundaries of our current understanding of complex biochemical, physiological, and environmental interactions, enabling proactive medicine in the near future. From this perspective, we review how state-of-the-art computational modelling of human metabolism, i.e., genome-scale metabolic modelling, could be used to identify the metabolic footprints of diseases, to guide the design of personalized treatments, and to estimate the microbiome contributions to host metabolism. These state-of-the-art models can serve as a scaffold for integrating multi-omics data, thereby enabling the identification of signatures of dysregulated metabolism by systems approaches. For example, increased plasma mannose levels due to decreased uptake in the liver have been identified as a potential biomarker of early insulin resistance by multi-omics approaches. In addition, we also review the emerging axis of human physiology and the human microbiome, discussing its contribution to host metabolism and quantitative approaches to study its variations in individuals.}, }
@article {pmid32978472, year = {2020}, author = {Daisley, BA and Pitek, AP and Chmiel, JA and Gibbons, S and Chernyshova, AM and Al, KF and Faragalla, KM and Burton, JP and Thompson, GJ and Reid, G}, title = {Lactobacillus spp. attenuate antibiotic-induced immune and microbiota dysregulation in honey bees.}, journal = {Communications biology}, volume = {3}, number = {1}, pages = {534}, pmid = {32978472}, issn = {2399-3642}, mesh = {Animals ; Anti-Bacterial Agents/*adverse effects ; Bees/*drug effects/immunology/microbiology ; Digestive System/immunology/microbiology ; Gastrointestinal Microbiome/*drug effects/immunology ; Lactobacillus/*drug effects/metabolism/physiology ; Larva/microbiology ; Oxytetracycline/*adverse effects ; }, abstract = {Widespread antibiotic usage in apiculture contributes substantially to the global dissemination of antimicrobial resistance and has the potential to negatively influence bacterial symbionts of honey bees (Apis mellifera). Here, we show that routine antibiotic administration with oxytetracycline selectively increased tetB (efflux pump resistance gene) abundance in the gut microbiota of adult workers while concurrently depleting several key symbionts known to regulate immune function and nutrient metabolism such as Frischella perrera and Lactobacillus Firm-5 strains. These microbial changes were functionally characterized by decreased capped brood counts (marker of hive nutritional status and productivity) and reduced antimicrobial capacity of adult hemolymph (indicator of immune competence). Importantly, combination therapy with three immunostimulatory Lactobacillus strains could mitigate antibiotic-associated microbiota dysbiosis and immune deficits in adult workers, as well as maximize the intended benefit of oxytetracycline by suppressing larval pathogen loads to near-undetectable levels. We conclude that microbial-based therapeutics may offer a simple but effective solution to reduce honey bee disease burden, environmental xenobiotic exposure, and spread of antimicrobial resistance.}, }
@article {pmid32976571, year = {2021}, author = {Gail, MH and Wan, Y and Shi, J}, title = {Power of Microbiome Beta-Diversity Analyses Based on Standard Reference Samples.}, journal = {American journal of epidemiology}, volume = {190}, number = {3}, pages = {439-447}, pmid = {32976571}, issn = {1476-6256}, mesh = {*Body Mass Index ; Feces/microbiology ; Humans ; Microbiota/*physiology ; Nose/microbiology ; Reference Standards ; Saliva/microbiology ; Skin/microbiology ; }, abstract = {A simple method to analyze microbiome beta-diversity computes mean beta-diversity distances from a test sample to standard reference samples. We used reference stool and nasal samples from the Human Microbiome Project and regressed an outcome on mean distances (2 degrees-of-freedom (df) test) or additionally on squares and cross-product of mean distances (5-df test). We compared the power of 2-df and 5-df tests with the microbiome regression-based kernel association test (MiRKAT). In simulations, MiRKAT had moderately greater power than the 2-df test for discriminating skin versus saliva and skin versus nasal samples, but differences were negligible for skin versus stool and stool versus nasal samples. The 2-df test had slightly greater power than MiRKAT for Dirichlet multinomial samples. In associating body mass index with beta-diversity in stool samples from the American Gut Project, the 5-df test yielded smaller P values than MiRKAT for most taxonomic levels and beta-diversity measures. Unlike procedures like MiRKAT that are based on the beta-diversity matrix, mean distances to reference samples can be analyzed with standard statistical tools and shared or meta-analyzed without sharing primary DNA data. Our data indicate that standard reference tests have power comparable to MiRKAT's (and to permutational multivariate analysis of variance), but more simulations and applications are needed to confirm this.}, }
@article {pmid32975912, year = {2020}, author = {Kim, GH and Rosiana, S and Kirienko, NV and Shapiro, RS}, title = {A Simple Nematode Infection Model for Studying Candida albicans Pathogenesis.}, journal = {Current protocols in microbiology}, volume = {59}, number = {1}, pages = {e114}, doi = {10.1002/cpmc.114}, pmid = {32975912}, issn = {1934-8533}, support = {//Canadian Institutes for Health Research/International ; }, mesh = {Animals ; Caenorhabditis elegans/microbiology ; Candida albicans/*pathogenicity ; Candidiasis/*microbiology ; Culture Media/chemistry ; Disease Models, Animal ; *Host-Pathogen Interactions ; Humans ; Kaplan-Meier Estimate ; Nematode Infections/*microbiology ; Virulence ; }, abstract = {Candida albicans is an opportunistic fungal pathogen and a model organism to study fungal pathogenesis. It exists as a harmless commensal organism and member of the healthy human microbiome, but can cause life-threatening mucosal and systemic infections. A model host to study C. albicans infection and pathogenesis is the nematode Caenorhabditis elegans. C. elegans is frequently used as a model host to study microbial-host interactions because it can be infected by many human pathogens and there are also close morphological resemblances between the intestinal cells of C. elegans and mammals, where C. albicans infections can occur. This article outlines a detailed methodology for exploiting C. elegans as a host to study C. albicans infection, including a C. elegans egg preparation protocol and an agar-based C. elegans killing protocol to monitor fungal virulence. These protocols can additionally be used to study C. albicans genetic mutants in order to further our understanding of the genes involved in pathogenesis and virulence in C. albicans and the mechanisms of host-microbe interactions. © 2020 Wiley Periodicals LLC. Basic Protocol 1: Preparation of Caenorhabditis elegans eggs Support Protocol 1: Freezing and recovering Caenorhabditis elegans Support Protocol 2: Making superfood agar and OP50 plates Basic Protocol 2: Caenorhabditis elegans/Candida albicans agar killing assay Support Protocol 3: Constructing a worm pick.}, }
@article {pmid32974330, year = {2020}, author = {Rasinkangas, P and Tytgat, HLP and Ritari, J and Reunanen, J and Salminen, S and Palva, A and Douillard, FP and de Vos, WM}, title = {Characterization of Highly Mucus-Adherent Non-GMO Derivatives of Lacticaseibacillus rhamnosus GG.}, journal = {Frontiers in bioengineering and biotechnology}, volume = {8}, number = {}, pages = {1024}, pmid = {32974330}, issn = {2296-4185}, support = {250172/ERC_/European Research Council/International ; }, abstract = {Lacticaseibacillus rhamnosus GG is one of the best studied lactic acid bacteria in the context of probiotic effects. L. rhamnosus GG has been shown to prevent diarrhea in children and adults and has been implicated to have mitigating or preventive effects in several disorders connected to microbiota dysbiosis. The probiotic effects are largely attributed to its adhesive heterotrimeric sortase-dependent pili, encoded by the spaCBA-srtC1 gene cluster. Indeed, the strain-specific SpaCBA pili have been shown to contribute to adherence, biofilm formation and host signaling. In this work we set out to generate non-GMO derivatives of L. rhamnosus GG that adhere stronger to mucus compared to the wild-type strain using chemical mutagenesis. We selected 13 derivatives that showed an increased mucus-adherent phenotype. Deep shotgun resequencing of the strains enabled division of the strains into three classes, two of which revealed SNPs (single nucleotide polymorphisms) in the spaA and spaC genes encoding the shaft and tip adhesive pilins, respectively. Strikingly, the other class derivatives demonstrated less clear genotype - phenotype relationships, illustrating that pili biogenesis and structure is also affected by other processes. Further characterization of the different classes of derivatives was performed by PacBio SMRT sequencing and RNAseq analysis, which resulted in the identification of molecular candidates driving pilin biosynthesis and functionality. In conclusion, we report on the generation and characterization of three classes of strongly adherent L. rhamnosus GG derivatives that show an increase in adhesion to mucus. These are of special interest as they provide a window on processes and genes driving piliation and its control in L. rhamnosus GG and offer a variety of non-GMO derivatives of this key probiotic strain that are applicable in food products.}, }
@article {pmid32973149, year = {2020}, author = {Daisley, BA and Chanyi, RM and Abdur-Rashid, K and Al, KF and Gibbons, S and Chmiel, JA and Wilcox, H and Reid, G and Anderson, A and Dewar, M and Nair, SM and Chin, J and Burton, JP}, title = {Abiraterone acetate preferentially enriches for the gut commensal Akkermansia muciniphila in castrate-resistant prostate cancer patients.}, journal = {Nature communications}, volume = {11}, number = {1}, pages = {4822}, pmid = {32973149}, issn = {2041-1723}, mesh = {Abiraterone Acetate/metabolism/*pharmacology/therapeutic use ; Akkermansia ; Androgen Antagonists/pharmacology ; Androgens/metabolism ; Bacteria/metabolism ; Feces/microbiology ; Gastrointestinal Microbiome/*drug effects ; Humans ; Male ; Prostatic Neoplasms/*drug therapy ; Prostatic Neoplasms, Castration-Resistant/*drug therapy ; RNA, Ribosomal, 16S/genetics ; Verrucomicrobia/*drug effects/genetics/metabolism ; Vitamin K 2/metabolism/pharmacology ; }, abstract = {Abiraterone acetate (AA) is an inhibitor of androgen biosynthesis, though this cannot fully explain its efficacy against androgen-independent prostate cancer. Here, we demonstrate that androgen deprivation therapy depletes androgen-utilizing Corynebacterium spp. in prostate cancer patients and that oral AA further enriches for the health-associated commensal, Akkermansia muciniphila. Functional inferencing elucidates a coinciding increase in bacterial biosynthesis of vitamin K2 (an inhibitor of androgen dependent and independent tumor growth). These results are highly reproducible in a host-free gut model, excluding the possibility of immune involvement. Further investigation reveals that AA is metabolized by bacteria in vitro and that breakdown components selectively impact growth. We conclude that A. muciniphila is a key regulator of AA-mediated restructuring of microbial communities, and that this species may affect treatment response in castrate-resistant cohorts. Ongoing initiatives aimed at modulating the colonic microbiota of cancer patients may consider targeted delivery of poorly absorbed selective bacterial growth agents.}, }
@article {pmid32972973, year = {2020}, author = {Balty, C and Guillot, A and Fradale, L and Brewee, C and Lefranc, B and Herrero, C and Sandström, C and Leprince, J and Berteau, O and Benjdia, A}, title = {Biosynthesis of the sactipeptide Ruminococcin C by the human microbiome: Mechanistic insights into thioether bond formation by radical SAM enzymes.}, journal = {The Journal of biological chemistry}, volume = {295}, number = {49}, pages = {16665-16677}, pmid = {32972973}, issn = {1083-351X}, mesh = {Amino Acid Sequence ; Bacterial Proteins/chemistry/genetics/*metabolism ; Bacteriocins/chemistry/genetics/*metabolism ; Biocatalysis ; Chromatography, High Pressure Liquid ; Clostridiales/*metabolism ; Humans ; Kinetics ; *Microbiota ; Multigene Family ; Mutagenesis, Site-Directed ; Recombinant Proteins/biosynthesis/chemistry/isolation &amp; purification ; Sterile Alpha Motif ; Substrate Specificity ; Sulfides/analysis/*chemistry/metabolism ; Tandem Mass Spectrometry ; }, abstract = {Despite its major importance in human health, the metabolic potential of the human gut microbiota is still poorly understood. We have recently shown that biosynthesis of Ruminococcin C (RumC), a novel ribosomally synthesized and posttranslationally modified peptide (RiPP) produced by the commensal bacterium Ruminococcus gnavus, requires two radical SAM enzymes (RumMC1 and RumMC2) catalyzing the formation of four Cα-thioether bridges. These bridges, which are essential for RumC's antibiotic properties against human pathogens such as Clostridium perfringens, define two hairpin domains giving this sactipeptide (sulfur-to-α-carbon thioether-containing peptide) an unusual architecture among natural products. We report here the biochemical and spectroscopic characterizations of RumMC2. EPR spectroscopy and mutagenesis data support that RumMC2 is a member of the large family of SPASM domain radical SAM enzymes characterized by the presence of three [4Fe-4S] clusters. We also demonstrate that this enzyme initiates its reaction by Cα H-atom abstraction and is able to catalyze the formation of nonnatural thioether bonds in engineered peptide substrates. Unexpectedly, our data support the formation of a ketoimine rather than an α,β-dehydro-amino acid intermediate during Cα-thioether bridge LC-MS/MS fragmentation. Finally, we explored the roles of the leader peptide and of the RiPP precursor peptide recognition element, present in myriad RiPP-modifying enzymes. Collectively, our data support a more complex role for the peptide recognition element and the core peptide for the installation of posttranslational modifications in RiPPs than previously anticipated and suggest a possible reaction intermediate for thioether bond formation.}, }
@article {pmid32971377, year = {2020}, author = {AlShahrani, I and Hosmani, J and AlShahrani, A and Togoo, RA and Syed, S and Yassin, SM and Chandramoorthy, HC and Devaraj, A}, title = {High altitude as a possible factor for dysbiosis of salivary microbiome in orthodontic patients.}, journal = {Archives of oral biology}, volume = {119}, number = {}, pages = {104917}, doi = {10.1016/j.archoralbio.2020.104917}, pmid = {32971377}, issn = {1879-1506}, mesh = {*Altitude ; Bacteria/classification ; *Dental Caries ; *Dysbiosis ; Humans ; *Microbiota ; RNA, Ribosomal, 16S/genetics ; Saliva/*microbiology ; }, abstract = {BACKGROUND: External stressors such as high altitude and low oxygen are known to affect the human microbiome, and in light of the increased occurrence of dental caries and periodontitis in orthodontic patients, the effect of high altitude and the altered oral environment in orthodontic patients on the oral salivary microbiome was researched.<br><br>MATERIALS &amp; METHODS: 31 orthodontic patients from high altitude, Aseer region and 25 orthodontic patients, residing at sea level, as controls were included. DNA isolation was done from the saliva collected from the study participants. V3 area of 16s RNA was targeted by universal primers through PCR to decipher the salivary microbiome in both the groups.<br><br>RESULTS: A total of 11 genera belonging to 4 phyla of bacteria were identified in both groups. The most abundant microbiome at the phylum level was: Firmicutes, Bacteroidetes Proteobacteria, and Cyanobacteria. The salivary microbiome was more diverse in sea level controls compared to that of the orthodontic patients at high altitude wherein the presence of only two main phyla: Firmicutes and Proteobacteria were seen. The controls revealed Firmicutes, Proteobacteria, Bacteroidetes and Cyanobacteria.<br><br>CONCLUSIONS: The findings of the study suggest that the biodiversity of the salivary microbiome is severely perturbed under the cumulative influences of high altitude and presence of fixed orthodontic appliance. Under these circumstances, a strict and meticulous oral hygiene regimen should be recommended and followed to avoid harmful effects on the periodontal tissues.}, }
@article {pmid32967314, year = {2020}, author = {Kim, B and Cho, EJ and Yoon, JH and Kim, SS and Cheong, JY and Cho, SW and Park, T}, title = {Pathway-Based Integrative Analysis of Metabolome and Microbiome Data from Hepatocellular Carcinoma and Liver Cirrhosis Patients.}, journal = {Cancers}, volume = {12}, number = {9}, pages = {}, pmid = {32967314}, issn = {2072-6694}, support = {HI16C2037//Ministry of Health and Welfare/ ; 2013M3A9C4078158//National Research Foundation of Korea/ ; }, abstract = {Aberrations of the human microbiome are associated with diverse liver diseases, including hepatocellular carcinoma (HCC). Even if we can associate specific microbes with particular diseases, it is difficult to know mechanistically how the microbe contributes to the pathophysiology. Here, we sought to reveal the functional potential of the HCC-associated microbiome with the human metabolome which is known to play a role in connecting host phenotype to microbiome function. To utilize both microbiome and metabolomic data sets, we propose an innovative, pathway-based analysis, Hierarchical structural Component Model for pathway analysis of Microbiome and Metabolome (HisCoM-MnM), for integrating microbiome and metabolomic data. In particular, we used pathway information to integrate these two omics data sets, thus providing insight into biological interactions between different biological layers, with regard to the host's phenotype. The application of HisCoM-MnM to data sets from 103 and 97 patients with HCC and liver cirrhosis (LC), respectively, showed that this approach could identify HCC-related pathways related to cancer metabolic reprogramming, in addition to the significant metabolome and metagenome that make up those pathways.}, }
@article {pmid32964353, year = {2020}, author = {Morar, N and Skorburg, JA}, title = {Why We Never Eat Alone: The Overlooked Role of Microbes and Partners in Obesity Debates in Bioethics.}, journal = {Journal of bioethical inquiry}, volume = {17}, number = {3}, pages = {435-448}, doi = {10.1007/s11673-020-10047-2}, pmid = {32964353}, issn = {1872-4353}, mesh = {*Bioethics ; Ethicists ; Humans ; Microbiota ; *Obesity ; }, abstract = {Debates about obesity in bioethics tend to unfold in predictable epicycles between individual choices and behaviours (e.g., restraint, diet, exercise) and the oppressive socio-economic structures constraining them (e.g., food deserts, advertising). Here, we argue that recent work from two cutting-edge research programmes in microbiology and social psychology can advance this conceptual stalemate in the literature. We begin in section 1 by discussing two promising lines of obesity research involving the human microbiome and relationship partners. Then, in section 2, we show how this research has made viable novel strategies for fighting obesity, including microbial therapies and dyad-level interventions. Finally, in section 3, we consider objections to our account and conclude by arguing that attention to the most immediate features of our biological and social environment offers a middle ground solution, while also raising important new issues for bioethicists.}, }
@article {pmid32961592, year = {2021}, author = {Sainz, T and Delgado, J and Mendez-Echevarría, A and Santiago, B and Lopez-Varela, E and Aguilera-Alonso, D and Saavedra-Lozano, J and Rodríguez-Fernández, R and Holguín, &#xc1; and Navarro, ML and Muñoz-Fernández, M&#xc1; and Rivero-Calle, I and Solana, MJ and López-Herce, J and Calvo, C}, title = {The clinical relevance of the microbiome when managing paediatric infectious diseases-Narrative review.}, journal = {Acta paediatrica (Oslo, Norway : 1992)}, volume = {110}, number = {2}, pages = {441-449}, doi = {10.1111/apa.15578}, pmid = {32961592}, issn = {1651-2227}, mesh = {Child ; *Communicable Diseases/therapy ; Humans ; *Microbiota ; }, abstract = {UNLABELLED: In recent years, the field of infectious diseases has been hit by the overwhelming amount of information generated while the human microbiome is being disentangled. Based on the interaction between the microbiota and the immune system, the implications regarding infectious diseases are probably major and remain a challenge.<br><br>AIMS: This review was conceived as a comprehensive tool to provide an overview of the available evidence regarding the influence of the microbiome on infectious diseases in children.<br><br>METHODS: We present the main findings aroused from microbiome research in prevention, diagnosis and treatment of infectious disease under a paediatric perspective, to inform clinicians of the potential relevance of microbiome-related knowledge for translation to clinical practice.<br><br>RESULTS AND CONCLUSION: The evidence shown in this review highlights the numerous research gaps ahead and supports the need to move forward to integrating the so-called microbiome thinking into our routine clinical practice.}, }
@article {pmid32958790, year = {2020}, author = {Sun, X and Li, M and Xia, L and Fang, Z and Yu, S and Gao, J and Feng, Q and Yang, P}, title = {Alteration of salivary microbiome in periodontitis with or without type-2 diabetes mellitus and metformin treatment.}, journal = {Scientific reports}, volume = {10}, number = {1}, pages = {15363}, pmid = {32958790}, issn = {2045-2322}, mesh = {Adult ; Bacteroidetes/genetics ; Diabetes Mellitus, Type 2/*drug therapy/microbiology ; Female ; Humans ; Hypoglycemic Agents/therapeutic use ; Male ; Metformin/*therapeutic use ; Microbiota/*genetics ; Middle Aged ; Periodontitis/*microbiology ; Prevotella/genetics ; RNA, Ribosomal, 16S/genetics ; Saliva/*microbiology ; }, abstract = {We aimed to explore the effects of type-2 diabetes mellitus (T2DM) and hypoglycemic therapy on the salivary microbiome in periodontitis patients and identify the potential salivary micro-biomarker for the early warning of T2DM. Saliva samples were collected from healthy individuals (Health), periodontitis patients (P), T2DM patients, periodontitis patients with T2DM (DAP), and DAP patients treated with Metformin (Met). Samples were determined by16S rRNA gene sequencing. 29 phyla, 322 genera, and 333 species of salivary microbiome were annotated. Compared to the Health group, the P and DAP group showed a significantly higher diversity of saliva microbiota, while the T2DM and Met group had no significant difference in microbial abundance but showed a trend of increasing diversity. Other than well-known periodontitis-inducing pathogens, the proportion of Prevotella copri, Alloprevotella rava, and Ralstonia pickettii, etc. were also significantly increased in periodontitis patients with or without T2DM. After effective glycemic control, the abundance of Prevotella copri, Alloprevotella rava, Ralstonia pickettii, etc. decreased in periodontitis patients with companion T2DM. The accuracies of the classification models in differentiating Health-vs.-P, DAP-vs.-P, and T2DM-vs.-P were 100%, 96.3%, and 98.1%, respectively. Hypoglycemic therapy could reconstruct the saliva microbiota and hence improve the localized conditions of diabetes patients with periodontitis.}, }
@article {pmid32958525, year = {2020}, author = {Pinto, D and Trink, A and Sorbellini, E and Giuliani, G and Rinaldi, F}, title = {'Omics' approaches for studying the microbiome in Alopecia areata.}, journal = {Journal of investigative medicine : the official publication of the American Federation for Clinical Research}, volume = {68}, number = {7}, pages = {1292-1294}, pmid = {32958525}, issn = {1708-8267}, mesh = {Alopecia Areata/*microbiology ; Gastrointestinal Microbiome ; *Genomics ; Humans ; *Microbiota ; Scalp/microbiology/pathology ; }, abstract = {Nowadays, the involvement of the microbiome in human health and many human diseases, including that strictly related to the scalphas been brought to the light. Indeed, more recently, authors highlighted the presence of a significant microbial shift both in nonscarring (Androgenetic alopecia and Alopecia areata) and scarring Alopecias. The advent of novel technologies together with the effort of many scientists in the microbiome field could provide in the nearest future a clearest framework about the strict relationship between human healthiness and symbiotic microorganism resident on different ecosystem of our body. In this view, the use of Omics approaches has to be considered as no longer negligible when studying the microbiome implication in human health and disease.}, }
@article {pmid32958509, year = {2020}, author = {Ormseth, MJ and Wu, Q and Zhao, S and Allen, RM and Solus, J and Sheng, Q and Guo, Y and Ye, F and Ramirez-Solano, M and Bridges, SL and Curtis, JR and Vickers, K and Stein, CM}, title = {Circulating microbial small RNAs are altered in patients with rheumatoid arthritis.}, journal = {Annals of the rheumatic diseases}, volume = {79}, number = {12}, pages = {1557-1564}, pmid = {32958509}, issn = {1468-2060}, support = {IK2 CX001269/CX/CSRD VA/United States ; P60 AR056116/AR/NIAMS NIH HHS/United States ; UL1 TR000445/TR/NCATS NIH HHS/United States ; }, mesh = {Adult ; Aged ; Antirheumatic Agents/therapeutic use ; Arthritis, Rheumatoid/*blood/*microbiology/pathology ; Cross-Sectional Studies ; Female ; Humans ; Male ; Middle Aged ; RNA, Bacterial/*blood/drug effects ; RNA, Fungal/*blood/drug effects ; RNA, Small Untranslated/*blood/drug effects ; }, abstract = {OBJECTIVES: To determine if plasma microbial small RNAs (sRNAs) are altered in patients with rheumatoid arthritis (RA) compared with control subjects, associated with RA disease-related features, and altered by disease-modifying antirheumatic drugs (DMARDs).<br><br>METHODS: sRNA sequencing was performed on plasma from 165 patients with RA and 90 matched controls and a separate cohort of 70 patients with RA before and after starting a DMARD. Genome alignments for RA-associated bacteria, representative bacterial and fungal human microbiome genomes and environmental bacteria were performed. Microbial genome counts and individual sRNAs were compared across groups and correlated with disease features. False discovery rate was set at 0.05.<br><br>RESULTS: Genome counts of Lactobacillus salivarius, Anaerobaculum hydrogeniformans, Staphylococcus epidermidis, Staphylococcus aureus, Paenisporosarcina spp, Facklamia hominis, Sphingobacterium spiritivorum, Lentibacillus amyloliquefaciens, Geobacillus spp, and Pseudomonas fluorescens were significantly decreased in the plasma of RA compared with control subjects. Three microbial transfer RNA-derived sRNAs were increased in RA versus controls and inversely associated with disease activity. Higher total microbial sRNA reads were associated with lower disease activity in RA. Baseline total microbial sRNAs were threefold higher among patients who improved with DMARD versus those who did not but did not change significantly after 6 months of treatment.<br><br>CONCLUSION: Plasma microbial sRNA composition is altered in RA versus control subjects and associated with some measures of RA disease activity. DMARD treatment does not alter microbial sRNA abundance or composition, but increased abundance of microbial sRNAs at baseline was associated with disease activity improvement at 6 months.}, }
@article {pmid32939371, year = {2020}, author = {Belkova, N and Klimenko, E and Vilson, N and Sambialova, A and Markova, D and Igumnov, I and Suturina, L}, title = {Metagenome datasets from women with polycystic ovary syndrome from Irkutsk, Eastern Siberia, Russia.}, journal = {Data in brief}, volume = {32}, number = {}, pages = {106137}, pmid = {32939371}, issn = {2352-3409}, abstract = {For the metagenomic characterization of potential taxonomic and functional diversity of microorganisms associated with polycystic ovary syndrome (PCOS) in women, we surveyed five women with PCOS and collected samples of feces, saliva, and serum. After quality processing, we have obtained from 915,594 to 3,880,379 reads; these 16,693 sequences had ribosomal RNA genes, 2,091,990 sequences contained predicted proteins with known functions, and 3,750,261 sequences had predicted proteins with unknown functions. Host DNA accounted for ca. 0.03% and less in datasets of fecal samples, from 1.41 to 24.94% in saliva samples; the remaining sequences were attributed to archaeal, bacterial, or viral DNA. In serum, from 38.18 to 75.77% were characterized as fragments of the human genome, but the remaining sequences were unidentified. Among microbes, a total of one archaeal and eight bacterial phyla were revealed. Viral DNA was detected in several fecal and one saliva sample and was classified as C2likevirus, Flavivirus, and Streptococcus bacteriophage. The metagenome sequence data were deposited at NCBI SRA as BioProject No. PRJNA625611.}, }
@article {pmid32939014, year = {2020}, author = {Yang, J and Moon, HE and Park, HW and McDowell, A and Shin, TS and Jee, YK and Kym, S and Paek, SH and Kim, YK}, title = {Brain tumor diagnostic model and dietary effect based on extracellular vesicle microbiome data in serum.}, journal = {Experimental &amp; molecular medicine}, volume = {52}, number = {9}, pages = {1602-1613}, pmid = {32939014}, issn = {2092-6413}, support = {NRF-2016M3A9B6901516//National Research Foundation of Korea (NRF)/ ; NRF-2020M3A9G80220292//National Research Foundation of Korea (NRF)/ ; 10050154//Ministry of Trade, Industry and Energy (Ministry of Trade, Industry and Energy, Korea)/ ; }, mesh = {Aged ; Animals ; Biomarkers, Tumor ; Brain Neoplasms/*diagnosis/*metabolism ; Case-Control Studies ; Computational Biology ; Diet ; Extracellular Vesicles/*metabolism/*microbiology ; Female ; Humans ; Machine Learning ; Male ; Metagenome ; Metagenomics/methods ; Mice ; *Microbiota ; Middle Aged ; ROC Curve ; }, abstract = {The human microbiome has been recently associated with human health and disease. Brain tumors (BTs) are a particularly difficult condition to directly link to the microbiome, as microorganisms cannot generally cross the blood-brain barrier (BBB). However, some nanosized extracellular vesicles (EVs) released from microorganisms can cross the BBB and enter the brain. Therefore, we conducted metagenomic analysis of microbial EVs in both serum (152 BT patients and 198 healthy controls (HC)) and brain tissue (5 BT patients and 5 HC) samples based on the V3-V4 regions of 16S rDNA. We then developed diagnostic models through logistic regression and machine learning algorithms using serum EV metagenomic data to assess the ability of various dietary supplements to reduce BT risk in vivo. Models incorporating the stepwise method and the linear discriminant analysis effect size (LEfSe) method yielded 12 and 29 significant genera as potential biomarkers, respectively. Models using the selected biomarkers yielded areas under the curves (AUCs) >0.93, and the model using machine learning resulted in an AUC of 0.99. In addition, Dialister and [Eubacterium] rectale were significantly lower in both blood and tissue samples of BT patients than in those of HCs. In vivo tests showed that BT risk was decreased through the addition of sorghum, brown rice oil, and garlic but conversely increased by the addition of bellflower and pear. In conclusion, serum EV metagenomics shows promise as a rich data source for highly accurate detection of BT risk, and several foods have potential for mitigating BT risk.}, }
@article {pmid32938697, year = {2020}, author = {Domingues, CPF and Rebelo, JS and Dionisio, F and Botelho, A and Nogueira, T}, title = {The Social Distancing Imposed To Contain COVID-19 Can Affect Our Microbiome: a Double-Edged Sword in Human Health.}, journal = {mSphere}, volume = {5}, number = {5}, pages = {}, pmid = {32938697}, issn = {2379-5042}, mesh = {Betacoronavirus ; *Biodiversity ; COVID-19/mortality/*prevention &amp; control ; Coronavirus Infections/mortality/*prevention &amp; control ; Dysbiosis/microbiology ; Humans ; *Microbiota ; Pandemics/*prevention &amp; control ; *Physical Distancing ; Pneumonia, Viral/mortality/*prevention &amp; control ; SARS-CoV-2 ; Social Networking ; }, abstract = {Hygienic measures imposed to control the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and contain COVID-19 have proven effective in controlling the pandemic. In this article, we argue that these measures could impact the human microbiome in two different and disparate ways, acting as a double-edged sword in human health. New lines of research have shown that the diversity of human intestinal and oropharyngeal microbiomes can shape pulmonary viral infection progression. Here, we suggest that the disruption in microbial sharing, as it is associated with dysbiosis (loss of bacterial diversity associated with an imbalance of the microbiota with deleterious consequences for the host), may worsen the prognosis of COVID-19 disease. In addition, social detachment can also decrease the rate of transmission of antibiotic-resistant bacteria. Therefore, it seems crucial to perform new studies combining the pandemic control of COVID-19 with the diversity of the human microbiome.}, }
@article {pmid32938362, year = {2020}, author = {Guerrini, V and Louza, FA and Rosone, G}, title = {Metagenomic analysis through the extended Burrows-Wheeler transform.}, journal = {BMC bioinformatics}, volume = {21}, number = {Suppl 8}, pages = {299}, pmid = {32938362}, issn = {1471-2105}, mesh = {*Algorithms ; High-Throughput Nucleotide Sequencing/*methods ; Humans ; Metagenomics/*methods ; Reproducibility of Results ; }, abstract = {BACKGROUND: The development of Next Generation Sequencing (NGS) has had a major impact on the study of genetic sequences. Among problems that researchers in the field have to face, one of the most challenging is the taxonomic classification of metagenomic reads, i.e., identifying the microorganisms that are present in a sample collected directly from the environment. The analysis of environmental samples (metagenomes) are particularly important to figure out the microbial composition of different ecosystems and it is used in a wide variety of fields: for instance, metagenomic studies in agriculture can help understanding the interactions between plants and microbes, or in ecology, they can provide valuable insights into the functions of environmental communities.<br><br>RESULTS: In this paper, we describe a new lightweight alignment-free and assembly-free framework for metagenomic classification that compares each unknown sequence in the sample to a collection of known genomes. We take advantage of the combinatorial properties of an extension of the Burrows-Wheeler transform, and we sequentially scan the required data structures, so that we can analyze unknown sequences of large collections using little internal memory. The tool LiME (Lightweight Metagenomics via eBWT) is available at https://github.com/veronicaguerrini/LiME .<br><br>CONCLUSIONS: In order to assess the reliability of our approach, we run several experiments on NGS data from two simulated metagenomes among those provided in benchmarking analysis and on a real metagenome from the Human Microbiome Project. The experiment results on the simulated data show that LiME is competitive with the widely used taxonomic classifiers. It achieves high levels of precision and specificity - e.g. 99.9% of the positive control reads are correctly assigned and the percentage of classified reads of the negative control is less than 0.01% - while keeping a high sensitivity. On the real metagenome, we show that LiME is able to deliver classification results comparable to that of MagicBlast. Overall, the experiments confirm the effectiveness of our method and its high accuracy even in negative control samples.}, }
@article {pmid32934239, year = {2020}, author = {Gupta, VK and Kim, M and Bakshi, U and Cunningham, KY and Davis, JM and Lazaridis, KN and Nelson, H and Chia, N and Sung, J}, title = {A predictive index for health status using species-level gut microbiome profiling.}, journal = {Nature communications}, volume = {11}, number = {1}, pages = {4635}, pmid = {32934239}, issn = {2041-1723}, mesh = {Bacteria/classification/genetics/*isolation &amp; purification ; Feces/microbiology ; *Gastrointestinal Microbiome ; *Health Status ; Humans ; Metagenome ; Microbiota ; }, abstract = {Providing insight into one's health status from a gut microbiome sample is an important clinical goal in current human microbiome research. Herein, we introduce the Gut Microbiome Health Index (GMHI), a biologically-interpretable mathematical formula for predicting the likelihood of disease independent of the clinical diagnosis. GMHI is formulated upon 50 microbial species associated with healthy gut ecosystems. These species are identified through a multi-study, integrative analysis on 4347 human stool metagenomes from 34 published studies across healthy and 12 different nonhealthy conditions, i.e., disease or abnormal bodyweight. When demonstrated on our population-scale meta-dataset, GMHI is the most robust and consistent predictor of disease presence (or absence) compared to α-diversity indices. Validation on 679 samples from 9 additional studies results in a balanced accuracy of 73.7% in distinguishing healthy from non-healthy groups. Our findings suggest that gut taxonomic signatures can predict health status, and highlight how data sharing efforts can provide broadly applicable discoveries.}, }
@article {pmid32928475, year = {2020}, author = {Blanchet, L and Vitale, R and van Vorstenbosch, R and Stavropoulos, G and Pender, J and Jonkers, D and Schooten, FV and Smolinska, A}, title = {Constructing bi-plots for random forest: Tutorial.}, journal = {Analytica chimica acta}, volume = {1131}, number = {}, pages = {146-155}, doi = {10.1016/j.aca.2020.06.043}, pmid = {32928475}, issn = {1873-4324}, abstract = {Current technological developments have allowed for a significant increase and availability of data. Consequently, this has opened enormous opportunities for the machine learning and data science field, translating into the development of new algorithms in a wide range of applications in medical, biomedical, daily-life, and national security areas. Ensemble techniques are among the pillars of the machine learning field, and they can be defined as approaches in which multiple, complex, independent/uncorrelated, predictive models are subsequently combined by either averaging or voting to yield a higher model performance. Random forest (RF), a popular ensemble method, has been successfully applied in various domains due to its ability to build predictive models with high certainty and little necessity of model optimization. RF provides both a predictive model and an estimation of the variable importance. However, the estimation of the variable importance is based on thousands of trees, and therefore, it does not specify which variable is important for which sample group. The present study demonstrates an approach based on the pseudo-sample principle that allows for construction of bi-plots (i.e. spin plots) associated with RF models. The pseudo-sample principle for RF. is explained and demonstrated by using two simulated datasets, and three different types of real data, which include political sciences, food chemistry and the human microbiome data. The pseudo-sample bi-plots, associated with RF and its unsupervised version, allow for a versatile visualization of multivariate models, and the variable importance and the relation among them.}, }
@article {pmid32917276, year = {2020}, author = {Golovko, G and Kamil, K and Albayrak, L and Nia, AM and Duarte, RSA and Chumakov, S and Fofanov, Y}, title = {Identification of multidimensional Boolean patterns in microbial communities.}, journal = {Microbiome}, volume = {8}, number = {1}, pages = {131}, pmid = {32917276}, issn = {2049-2618}, support = {R03 DE028596/DE/NIDCR NIH HHS/United States ; }, mesh = {Bacteria/isolation &amp; purification ; Humans ; *Microbial Interactions ; *Microbiota/physiology ; }, abstract = {BACKGROUND: Identification of complex multidimensional interaction patterns within microbial communities is the key to understand, modulate, and design beneficial microbiomes. Every community has members that fulfill an essential function affecting multiple other community members through secondary metabolism. Since microbial community members are often simultaneously involved in multiple relations, not all interaction patterns for such microorganisms are expected to exhibit a visually uninterrupted pattern. As a result, such relations cannot be detected using traditional correlation, mutual information, principal coordinate analysis, or covariation-based network inference approaches.<br><br>RESULTS: We present a novel pattern-specific method to quantify the strength and estimate the statistical significance of two-dimensional co-presence, co-exclusion, and one-way relation patterns between abundance profiles of two organisms as well as extend this approach to allow search and visualize three-, four-, and higher dimensional patterns. The proposed approach has been tested using 2380 microbiome samples from the Human Microbiome Project resulting in body site-specific networks of statistically significant 2D patterns as well as revealed the presence of 3D patterns in the Human Microbiome Project data.<br><br>CONCLUSIONS: The presented study suggested that search for Boolean patterns in the microbial abundance data needs to be pattern specific. The reported presence of multidimensional patterns (which cannot be reduced to a combination of two-dimensional patterns) suggests that multidimensional (multi-organism) relations may play important roles in the organization of microbial communities, and their detection (and appropriate visualization) may lead to a deeper understanding of the organization and dynamics of microbial communities. Video Abstract.}, }
@article {pmid32916129, year = {2020}, author = {Mars, RAT and Yang, Y and Ward, T and Houtti, M and Priya, S and Lekatz, HR and Tang, X and Sun, Z and Kalari, KR and Korem, T and Bhattarai, Y and Zheng, T and Bar, N and Frost, G and Johnson, AJ and van Treuren, W and Han, S and Ordog, T and Grover, M and Sonnenburg, J and D'Amato, M and Camilleri, M and Elinav, E and Segal, E and Blekhman, R and Farrugia, G and Swann, JR and Knights, D and Kashyap, PC}, title = {Longitudinal Multi-omics Reveals Subset-Specific Mechanisms Underlying Irritable Bowel Syndrome.}, journal = {Cell}, volume = {182}, number = {6}, pages = {1460-1473.e17}, pmid = {32916129}, issn = {1097-4172}, support = {P30 DK084567/DK/NIDDK NIH HHS/United States ; R01 DK114007/DK/NIDDK NIH HHS/United States ; R35 GM128716/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Bile Acids and Salts/metabolism ; Biopsy ; Butyrates/metabolism ; Chromatography, Liquid ; Cross-Sectional Studies ; Epigenomics ; Feces/microbiology ; Female ; Gastrointestinal Microbiome/*genetics/physiology ; Gene Expression Regulation/*genetics/physiology ; Host Microbial Interactions/genetics ; Humans ; Hypoxanthine/metabolism ; Irritable Bowel Syndrome/genetics/*metabolism/microbiology ; Longitudinal Studies ; Male ; *Metabolome/physiology ; Mice ; Observational Studies as Topic ; Prospective Studies ; Purines/*metabolism ; Software ; Tandem Mass Spectrometry ; Transcriptome/*genetics/physiology ; }, abstract = {The gut microbiome has been implicated in multiple human chronic gastrointestinal (GI) disorders. Determining its mechanistic role in disease has been difficult due to apparent disconnects between animal and human studies and lack of an integrated multi-omics view of disease-specific physiological changes. We integrated longitudinal multi-omics data from the gut microbiome, metabolome, host epigenome, and transcriptome in the context of irritable bowel syndrome (IBS) host physiology. We identified IBS subtype-specific and symptom-related variation in microbial composition and function. A subset of identified changes in microbial metabolites correspond to host physiological mechanisms that are relevant to IBS. By integrating multiple data layers, we identified purine metabolism as a novel host-microbial metabolic pathway in IBS with translational potential. Our study highlights the importance of longitudinal sampling and integrating complementary multi-omics data to identify functional mechanisms that can serve as therapeutic targets in a comprehensive treatment strategy for chronic GI diseases. VIDEO ABSTRACT.}, }
@article {pmid32915102, year = {2020}, author = {Taddese, R and Garza, DR and Ruiter, LN and de Jonge, MI and Belzer, C and Aalvink, S and Nagtegaal, ID and Dutilh, BE and Boleij, A}, title = {Growth rate alterations of human colorectal cancer cells by 157 gut bacteria.}, journal = {Gut microbes}, volume = {12}, number = {1}, pages = {1-20}, pmid = {32915102}, issn = {1949-0984}, mesh = {Bacteria/genetics/pathogenicity ; *Bacterial Physiological Phenomena ; Cell Line ; Cell Line, Tumor ; Cell Proliferation ; Colorectal Neoplasms/*pathology ; Gastrointestinal Microbiome/*physiology ; Gastrointestinal Tract/*microbiology ; Humans ; Species Specificity ; Virulence/genetics ; }, abstract = {Several bacteria in the human gut microbiome have been associated with colorectal cancer (CRC) by high-throughput screens. In some cases, molecular mechanisms have been elucidated that drive tumorigenesis, including bacterial membrane proteins or secreted molecules that interact with the human cancer cells. For most gut bacteria, however, it remains unknown if they enhance or inhibit cancer cell growth. Here, we screened bacteria-free supernatants (secretomes) and inactivated cells of over 150 cultured bacterial strains for their effects on cell growth. We observed family-level and strain-level effects that often differed between bacterial cells and secretomes, suggesting that different molecular mechanisms are at play. Secretomes of Bacteroidaceae, Enterobacteriaceae, and Erysipelotrichaceae bacteria enhanced cell growth, while most Fusobacteriaceae cells and secretomes inhibited growth, contrasting prior findings. In some bacteria, the presence of specific functional genes was associated with cell growth rates, including the virulence genes TcdA, TcdB in Clostridiales and FadA in Fusobacteriaceae, which both inhibited growth. Bacteroidaceae cells that enhanced growth were enriched for genes of the cobalamin synthesis pathway, while Fusobacteriaceae cells that inhibit growth were enriched for genes of the ethanolamine utilization pathway. Together, our results reveal how different gut bacteria have wide-ranging effects on cell growth, contribute a better understanding of the effects of the gut microbiome on host cells, and provide a valuable resource for identifying candidate target genes for potential microbiome-based diagnostics and treatment strategies.}, }
@article {pmid32914503, year = {2020}, author = {Koponen, A and Pan, G and Kivelä, AM and Ralko, A and Taskinen, JH and Arora, A and Kosonen, R and Kari, OK and Ndika, J and Ikonen, E and Cho, W and Yan, D and Olkkonen, VM}, title = {ORP2, a cholesterol transporter, regulates angiogenic signaling in endothelial cells.}, journal = {FASEB journal : official publication of the Federation of American Societies for Experimental Biology}, volume = {34}, number = {11}, pages = {14671-14694}, doi = {10.1096/fj.202000202R}, pmid = {32914503}, issn = {1530-6860}, support = {R35GM122530//The National Institutes of Health/ ; }, mesh = {Actins/metabolism ; Antigens, CD/metabolism ; Cadherins/metabolism ; Caveolins/metabolism ; Cell Membrane/metabolism ; Cell Movement ; Endosomes/metabolism ; Human Umbilical Vein Endothelial Cells/*metabolism/physiology ; Humans ; Matrix Metalloproteinases/metabolism ; *Neovascularization, Physiologic ; Nitric Oxide Synthase Type III/metabolism ; Phosphatidylinositol 4,5-Diphosphate/metabolism ; Proto-Oncogene Proteins c-akt/metabolism ; Receptors, Notch/metabolism ; Receptors, Steroid/genetics/*metabolism ; Receptors, Vascular Endothelial Growth Factor/metabolism ; *Signal Transduction ; TOR Serine-Threonine Kinases/metabolism ; }, abstract = {Oxysterol-binding protein-related protein 2 (ORP2), a cholesterol-PI(4,5)P2 countercurrent transporter, was recently identified as a novel regulator of plasma membrane (PM) cholesterol and PI(4,5)P2 content in HeLa cells. Here, we investigate the role of ORP2 in endothelial cell (EC) cholesterol and PI(4,5)P2 distribution, angiogenic signaling, and angiogenesis. We show that ORP2 knock-down modifies the distribution of cholesterol accessible to a D4H probe, between late endosomes and the PM. Depletion of ORP2 from ECs inhibits their angiogenic tube formation capacity, alters the gene expression of angiogenic signaling pathways such as VEGFR2, Akt, mTOR, eNOS, and Notch, and reduces EC migration, proliferation, and cell viability. We show that ORP2 regulates the integrity of VEGFR2 at the PM in a cholesterol-dependent manner, the depletion of ORP2 resulting in proteolytic cleavage by matrix metalloproteinases, and reduced activity of VEGFR2 and its downstream signaling. We demonstrate that ORP2 depletion increases the PM PI(4,5)P2 coincident with altered F-actin morphology, and reduces both VEGFR2 and cholesterol in buoyant raft membranes. Moreover, ORP2 knock-down suppresses the expression of the lipid raft-associated proteins VE-cadherin and caveolin-1. Analysis of the retinal microvasculature in ORP2 knock-out mice generated during this study demonstrates the subtle alterations of morphology characterized by reduced vessel length and increased density of tip cells and perpendicular sprouts. Gene expression changes in the retina suggest disturbance of sterol homeostasis, downregulation of VE-cadherin, and a putative disturbance of Notch signaling. Our data identifies ORP2 as a novel regulator of EC cholesterol and PI(4,5)P2 homeostasis and cholesterol-dependent angiogenic signaling.}, }
@article {pmid32912857, year = {2021}, author = {Feng, Q and Lan, X and Ji, X and Li, M and Liu, S and Xiong, J and Yu, Y and Liu, Z and Xu, Z and He, L and Chen, Y and Dong, H and Chen, P and Chen, B and He, K and Li, Y}, title = {Time series analysis of microbiome and metabolome at multiple body sites in steady long-term isolation confinement.}, journal = {Gut}, volume = {70}, number = {7}, pages = {1409-1412}, doi = {10.1136/gutjnl-2020-320666}, pmid = {32912857}, issn = {1468-3288}, mesh = {Humans ; Metabolome ; *Microbiota ; Time Factors ; }, }
@article {pmid32908210, year = {2020}, author = {Sharma, A and Im, SH}, title = {Special issue on the human microbiome: from symbiosis to therapy.}, journal = {Experimental &amp; molecular medicine}, volume = {52}, number = {9}, pages = {1361-1363}, pmid = {32908210}, issn = {2092-6413}, mesh = {Disease Management ; Disease Susceptibility ; Dysbiosis ; *Homeostasis ; *Host Microbial Interactions ; Host-Pathogen Interactions ; Humans ; *Microbiota ; Symbiosis ; }, }
@article {pmid32907948, year = {2020}, author = {Al, KF and Daisley, BA and Chanyi, RM and Bjazevic, J and Razvi, H and Reid, G and Burton, JP}, title = {Oxalate-Degrading Bacillus subtilis Mitigates Urolithiasis in a Drosophila melanogaster Model.}, journal = {mSphere}, volume = {5}, number = {5}, pages = {}, pmid = {32907948}, issn = {2379-5042}, mesh = {Animals ; Bacillus subtilis/*metabolism ; Calcium Oxalate/*metabolism ; Disease Models, Animal ; Dogs ; Drosophila melanogaster/microbiology ; Female ; High-Throughput Screening Assays ; Intestines/microbiology ; Madin Darby Canine Kidney Cells ; Male ; Urolithiasis/drug therapy/*microbiology ; }, abstract = {Kidney stones affect nearly 10% of the population in North America and are associated with high morbidity and recurrence, yet novel prevention strategies are lacking. Recent evidence suggests that the human gut microbiota can influence the development of nephrolithiasis, although clinical trials have been limited and inconclusive in determining the potential for microbially based interventions. Here, we used an established Drosophila melanogaster model of urolithiasis as a high-throughput screening platform for evaluation of the therapeutic potential of oxalate-degrading bacteria in calcium oxalate (CaOx) nephrolithiasis. The results demonstrated that Bacillus subtilis 168 (BS168) is a promising candidate based on its preferential growth in high oxalate concentrations, its ability to stably colonize the D. melanogaster intestinal tract for as long as 5 days, and its prevention of oxalate-induced microbiota dysbiosis. Single-dose BS168 supplementation exerted beneficial effects on D. melanogaster for as long as 14 days, decreasing stone burden in dissected Malpighian tubules and fecal excreta while increasing survival and behavioral markers of health over those of nonsupplemented lithogenic controls. These findings were complemented by in vitro experiments using the established MDCK renal cell line, which demonstrated that BS168 pretreatment prevented increased CaOx crystal adhesion and aggregation. Taking our results together, this study supports the notion that BS168 can functionally reduce CaOx stone burden in vivo through its capacity for oxalate degradation. Given the favorable safety profile of many B. subtilis strains already used as digestive aids and in fermented foods, these findings suggest that BS168 could represent a novel therapeutic adjunct to reduce the incidence of recurrent CaOx nephrolithiasis in high-risk patients.IMPORTANCE Kidney stone disease is a morbid condition that is increasing in prevalence, with few nonsurgical treatment options. The majority of stones are composed of calcium oxalate. Unlike humans, some microbes can break down oxalate, suggesting that microbial therapeutics may provide a novel treatment for kidney stone patients. This study demonstrated that Bacillus subtilis 168 (BS168) decreased stone burden, improved health, and complemented the microbiota in a Drosophila melanogaster urolithiasis model, while not exacerbating calcium oxalate aggregation or adhesion to renal cells in vitro These results identify this bacterium as a candidate for ameliorating stone formation; given that other strains of B. subtilis are components of fermented foods and are used as probiotics for digestive health, strain 168 warrants testing in humans. With the severe burden that recurrent kidney stone disease imposes on patients and the health care system, this microbial therapeutic approach could provide an inexpensive therapeutic adjunct.}, }
@article {pmid32901266, year = {2021}, author = {Giangaspero, A and Barlaam, A and Pane, S and Marchili, MR and Onetti Muda, A and Putignani, L and Hall, MJR}, title = {Accidental Nasal Myiasis Caused by Megaselia rufipes (Diptera: Phoridae) in a Child.}, journal = {Journal of medical entomology}, volume = {58}, number = {1}, pages = {121-124}, doi = {10.1093/jme/tjaa184}, pmid = {32901266}, issn = {1938-2928}, mesh = {Animals ; Child, Preschool ; *Diptera/classification/genetics/pathogenicity ; Electron Transport Complex IV/genetics ; Genes, Insect ; Humans ; Italy ; Larva ; Myiasis/*diagnosis ; Nose/parasitology ; Phylogeny ; }, abstract = {A case of a nasal myiasis in a 3-yr-old Italian girl who was referred to Bambino Gesù Hospital in Rome, Italy, is reported. Larvae discharged with the nasal mucus were microscopically identified as Megaselia spp.; DNA barcoding analysis showed that they belonged to the 'scuttle fly' species Megaselia rufipes (Meigen). Based on the patient's history, she became infected when she played outside. This is the first report of myiasis in humans due to M. rufipes (Diptera: Phoridae).}, }
@article {pmid32901128, year = {2021}, author = {Federici, S and Nobs, SP and Elinav, E}, title = {Phages and their potential to modulate the microbiome and immunity.}, journal = {Cellular &amp; molecular immunology}, volume = {18}, number = {4}, pages = {889-904}, pmid = {32901128}, issn = {2042-0226}, support = {/HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Animals ; Bacteria/*immunology/virology ; Bacterial Infections/immunology/microbiology/*therapy ; Bacteriophages/*growth &amp; development ; *Drug Resistance, Multiple, Bacterial ; Humans ; Phage Therapy/*methods ; }, abstract = {Bacteriophages (hence termed phages) are viruses that target bacteria and have long been considered as potential future treatments against antibiotic-resistant bacterial infection. However, the molecular nature of phage interactions with bacteria and the human host has remained elusive for decades, limiting their therapeutic application. While many phages and their functional repertoires remain unknown, the advent of next-generation sequencing has increasingly enabled researchers to decode new lytic and lysogenic mechanisms by which they attack and destroy bacteria. Furthermore, the last decade has witnessed a renewed interest in the utilization of phages as therapeutic vectors and as a means of targeting pathogenic or commensal bacteria or inducing immunomodulation. Importantly, the narrow host range, immense antibacterial repertoire, and ease of manipulating phages may potentially allow for their use as targeted modulators of pathogenic, commensal and pathobiont members of the microbiome, thereby impacting mammalian physiology and immunity along mucosal surfaces in health and in microbiome-associated diseases. In this review, we aim to highlight recent advances in phage biology and how a mechanistic understanding of phage-bacteria-host interactions may facilitate the development of novel phage-based therapeutics. We provide an overview of the challenges of the therapeutic use of phages and how these could be addressed for future use of phages as specific modulators of the human microbiome in a variety of infectious and noncommunicable human diseases.}, }
@article {pmid32898133, year = {2020}, author = {Chen, B and Xu, W}, title = {Generalized estimating equation modeling on correlated microbiome sequencing data with longitudinal measures.}, journal = {PLoS computational biology}, volume = {16}, number = {9}, pages = {e1008108}, pmid = {32898133}, issn = {1553-7358}, mesh = {Computational Biology/*methods ; *DNA, Bacterial/classification/genetics ; Databases, Genetic ; Gastrointestinal Microbiome/*genetics ; Humans ; *Models, Statistical ; Sequence Analysis, DNA/*methods ; }, abstract = {Existing models for assessing microbiome sequencing such as operational taxonomic units (OTUs) can only test predictors' effects on OTUs. There is limited work on how to estimate the correlations between multiple OTUs and incorporate such relationship into models to evaluate longitudinal OTU measures. We propose a novel approach to estimate OTU correlations based on their taxonomic structure, and apply such correlation structure in Generalized Estimating Equations (GEE) models to estimate both predictors' effects and OTU correlations. We develop a two-part Microbiome Taxonomic Longitudinal Correlation (MTLC) model for multivariate zero-inflated OTU outcomes based on the GEE framework. In addition, longitudinal and other types of repeated OTU measures are integrated in the MTLC model. Extensive simulations have been conducted to evaluate the performance of the MTLC method. Compared with the existing methods, the MTLC method shows robust and consistent estimation, and improved statistical power for testing predictors' effects. Lastly we demonstrate our proposed method by implementing it into a real human microbiome study to evaluate the obesity on twins.}, }
@article {pmid32888342, year = {2020}, author = {Reyes-Gibby, CC and Wang, J and Zhang, L and Peterson, CB and Do, KA and Jenq, RR and Shelburne, S and Shah, DP and Chambers, MS and Hanna, EY and Yeung, SJ and Shete, S}, title = {Oral microbiome and onset of oral mucositis in patients with squamous cell carcinoma of the head and neck.}, journal = {Cancer}, volume = {126}, number = {23}, pages = {5124-5136}, pmid = {32888342}, issn = {1097-0142}, support = {RP160693//Cancer Prevention and Research Institute of Texas/ ; R01 CA131324/CA/NCI NIH HHS/United States ; P50 CA140388/CA/NCI NIH HHS/United States ; P50CA140388/CA/NCI NIH HHS/United States ; RP170259//Cancer Prevention and Research Institute of Texas/ ; UL1 TR003167/TR/NCATS NIH HHS/United States ; 1R01CA131324/CA/NCI NIH HHS/United States ; R01DE022891/DE/NIDCR NIH HHS/United States ; R21DE026837/DE/NIDCR NIH HHS/United States ; CA016672/CA/NCI NIH HHS/United States ; //Betty B. Marcus Chair in Cancer Prevention/ ; R21 DE026837/DE/NIDCR NIH HHS/United States ; R01 DE022891/DE/NIDCR NIH HHS/United States ; P30 CA016672/CA/NCI NIH HHS/United States ; }, mesh = {Aged ; Female ; Head and Neck Neoplasms/microbiology/*therapy ; Humans ; Male ; *Microbiota/drug effects/radiation effects ; Middle Aged ; RNA, Ribosomal, 16S ; Squamous Cell Carcinoma of Head and Neck/microbiology/*therapy ; Stomatitis/*etiology/microbiology ; Time Factors ; }, abstract = {BACKGROUND: Oral mucositis (OM) is a debilitating sequela for patients treated for squamous cell carcinoma of the head and neck (HNSCC). This study investigated whether oral microbial features before treatment or during treatment are associated with the time to onset of severe OM in patients with HNSCC.<br><br>METHODS: This was a cohort study of newly diagnosed patients with locoregional HNSCC who received chemotherapy with or without radiotherapy from April 2016 to September 2017. OM was based on the National Cancer Institute's Common Terminology Criteria for Adverse Events, version 4.0. The oral microbiome was characterized on the basis of the 16S ribosomal RNA V4 region with the Illumina platform. A mixture cure model was used to generate hazard ratios for the onset of severe OM.<br><br>RESULTS: Eighty-six percent of the patients developed OM (n&#xa0;=&#xa0;57 [33 nonsevere cases and 24 severe cases]) with a median time to onset of OM of 21 days. With adjustments for age, sex, and smoking status, genera abundance was associated with the hazard for the onset of severe OM as follows: 1) at the baseline (n&#xa0;=&#xa0;66), Cardiobacterium (P&#xa0;=&#xa0;.03) and Granulicatella (P&#xa0;=&#xa0;.04); 2) immediately before the development of OM (n&#xa0;=&#xa0;57), Prevotella (P&#xa0;=&#xa0;.03), Fusobacterium (P&#xa0;=&#xa0;.03), and Streptococcus (P&#xa0;=&#xa0;.01); and 3) immediately before the development of severe OM (n&#xa0;=&#xa0;24), Megasphaera (P&#xa0;=&#xa0;.0001) and Cardiobacterium (P&#xa0;=&#xa0;.03). There were no differences in &#x3b1;-diversity between the baseline samples and Human Microbiome Project data.<br><br>CONCLUSIONS: Changes in the abundance of genera over the course of treatment were associated with the onset of severe OM. The mechanism and therapeutic implications of these findings need to be investigated in future studies.}, }
@article {pmid32887714, year = {2020}, author = {García, MG and Pérez-Cárceles, MD and Osuna, E and Legaz, I}, title = {Impact of the Human Microbiome in Forensic Sciences: a Systematic Review.}, journal = {Applied and environmental microbiology}, volume = {86}, number = {22}, pages = {}, pmid = {32887714}, issn = {1098-5336}, mesh = {Bacteria/classification/*isolation &amp; purification ; *Bacterial Physiological Phenomena ; *Forensic Sciences ; Humans ; *Microbiota ; }, abstract = {Numerous studies relate differences in microbial communities to human health and disease; however, little is known about microbial changes that occur postmortem or the possible applications of microbiome analysis in the field of forensic science. The aim of this review was to study the microbiome and its applications in forensic sciences and to determine the main lines of investigation that are emerging, as well as its possible contributions to the forensic field. A systematic review of the human microbiome in relation to forensic science was carried out by following PRISMA guidelines. This study sheds light on the role of microbiome research in the postmortem interval during the process of decomposition, identifying death caused by drowning or sudden death, locating the geographical location of death, establishing a connection between the human microbiome and personal items, sexual contact, and the identification of individuals. Actinomycetaceae, Bacteroidaceae, Alcaligenaceae, and Bacilli play an important role in determining the postmortem interval. Aeromonas can be used to determine the cause of death, and Corynebacterium or Helicobacter pylori can be used to ascertain personal identity or geographical location. Several studies point to a promising future for microbiome analysis in the different fields of forensic science, opening up an important new area of research.}, }
@article {pmid32885090, year = {2020}, author = {Suojanen, LU and Ahola, AJ and Kupila, S and Korpela, R and Pietiläinen, KH}, title = {Effectiveness of a web-based real-life weight management program: Study design, methods, and participants' baseline characteristics.}, journal = {Contemporary clinical trials communications}, volume = {19}, number = {}, pages = {100638}, pmid = {32885090}, issn = {2451-8654}, abstract = {UNLABELLED: Obesity is an important public health concern with limited effective treatment options. Internet-based technologies offer a cost-effective means to treat obesity. However, most of the online programs have been of short duration, have focused on a limited number of treatment modalities, and have not utilized the potential of coaching as part of the intervention. In this paper, we present the design, methods and participants' baseline characteristics in a real-life internet-based weight management program. Healthy Weight Coaching (HWC) is a 12-month web-based intervention for the management of obesity. The program is based on the Acceptance and Commitment Therapy and includes themes important for weight loss, including diet, physical activity, psychological factors, and sleep. In addition to the automated, interactive program, a personal coach is allocated to each participant. The participants are nationally enrolled through referrals from primary care, occupational health, hospitals, and private health care units. Adult individuals with BMI ≥25 kg/m[2] without severe complications are included. On a weekly basis, participants submit their weight logs, training sessions, and lifestyle targets to the internet portal and are scheduled to have online discussions with their coaches 26 times over the course of a year. Questionnaires on lifestyle, diet, physical activity, psychological factors, sleep, and quality of life are completed at baseline, 3, 6, 9, and 12 months, and thereafter yearly until 5 years. Additionally, log data on the use of the service and discussions with the coach are collected. The main outcome is weight change from baseline to 12 months. Recruitment to the HWC is ongoing. Baseline data of the participants recruited between Oct 2016 and Mar 2019 (n = 1189) are provided. This research will bring insight into how internet-based technologies can be implemented in the virtual management of obesity.<br><br>TRIAL REGISTRATION: The trial is registered at clinicaltrials.cov (Clinical Trials Identifier NCT04019249).}, }
@article {pmid32884579, year = {2020}, author = {Katongole, P and Sande, OJ and Joloba, M and Reynolds, SJ and Niyonzima, N}, title = {The human microbiome and its link in prostate cancer risk and pathogenesis.}, journal = {Infectious agents and cancer}, volume = {15}, number = {}, pages = {53}, pmid = {32884579}, issn = {1750-9378}, support = {D43 TW010132/TW/FIC NIH HHS/United States ; }, abstract = {There is growing evidence of the microbiome's role in human health and disease since the human microbiome project. The microbiome plays a vital role in influencing cancer risk and pathogenesis. Several studies indicate microbial pathogens to account for over 15-20% of all cancers. Furthermore, the interaction of the microbiota, especially the gut microbiota in influencing response to chemotherapy, immunotherapy, and radiotherapy remains an area of active research. Certain microbial species have been linked to the improved clinical outcome when on different cancer therapies. The recent discovery of the urinary microbiome has enabled the study to understand its connection to genitourinary malignancies, especially prostate cancer. Prostate cancer is the second most common cancer in males worldwide. Therefore research into understanding the factors and mechanisms associated with prostate cancer etiology, pathogenesis, and disease progression is of utmost importance. In this review, we explore the current literature concerning the link between the gut and urinary microbiome and prostate cancer risk and pathogenesis.}, }
@article {pmid32882798, year = {2020}, author = {Jiang, Q and Kainulainen, V and Stamatova, I and Janket, SJ and Meurman, JH and Korpela, R}, title = {Mouthwash Effects on LGG-Integrated Experimental Oral Biofilms.}, journal = {Dentistry journal}, volume = {8}, number = {3}, pages = {}, pmid = {32882798}, issn = {2304-6767}, support = {201206310016//China Scholarship Council/ ; 285632//Academy of Finland/ ; }, abstract = {In order to investigate the effects of mouthwashes on oral biofilms with probiotics, we compared in biofilms the susceptibility to mouthwashes of probiotic Lactobacillus rhamnosus GG (LGG) and oral pathogens Streptococcus mutans, Streptococcus sanguinis, and Candida albicans. We also evaluated these pathogens' susceptibility to the mouthwashes and their recovery after mouthwash-rinsing in biofilms with/without LGG. First, 1-day-/3-day-old LGG-integrated multi-species biofilms were exposed for 1 min to mouthwashes containing chlorhexidine, essential oils, or amine fluoride/stannous fluoride. Cells were plate-counted and relative survival rates (RSRs) of LGG and pathogens calculated. Second, 1-day-/3-day-old multispecies biofilms with and without LGG were exposed for 1 min to mouthwashes; cells were plate-counted and the pathogens' RSRs were calculated. Third, 1-day-old biofilms were treated for 1 min with mouthwashes. Cells were plate-counted immediately and after 2-day cultivation. Recovery rates of pathogens were calculated and compared between biofilms with/without LGG. Live/Dead[®] staining served for structural analyses. Our results showed that RSRs of LGG were insignificantly smaller than those of pathogens in both 1-day and 3-day biofilms. No significant differences appeared in pathogens' RSRs and recovery rates after treatment between biofilms with/without LGG. To conclude, biofilm LGG was susceptible to the mouthwashes; but biofilm LGG altered neither the mouthwash effects on oral pathogens nor affected their recovery.}, }
@article {pmid32879794, year = {2020}, author = {Odogwu, NM and Olayemi, OO and Omigbodun, AO}, title = {The vaginal microbiome of sub-Saharan African women: revealing important gaps in the era of next-generation sequencing.}, journal = {PeerJ}, volume = {8}, number = {}, pages = {e9684}, pmid = {32879794}, issn = {2167-8359}, abstract = {Accurate characterization of the vaginal microbiome remains a fundamental goal of the Human Microbiome project (HMP). For over a decade, this goal has been made possible deploying high-throughput next generation sequencing technologies (NGS), which indeed has revolutionized medical research and enabled large-scale genomic studies. The 16S rRNA marker-gene survey is the most commonly explored approach for vaginal microbial community studies. With this approach, prior studies have elucidated substantial variations in the vaginal microbiome of women from different ethnicities. This review provides a comprehensive account of studies that have deployed this approach to describe the vaginal microbiota of African women in health and disease. On the basis of published data, the few studies reported from the African population are mainly in non-pregnant post pubertal women and calls for more detailed studies in pregnant and postnatal cohorts. We provide insight on the use of more sophisticated cutting-edge technologies in characterizing the vaginal microbiome. These technologies offer high-resolution detection of vaginal microbiome variations and community functional capabilities, which can shed light into several discrepancies observed in the vaginal microbiota of African women in an African population versus women of African descent in the diaspora.}, }
@article {pmid32878769, year = {2020}, author = {Halley, A and Leonetti, A and Gregori, A and Tiseo, M and Deng, DM and Giovannetti, E and Peters, GJ}, title = {The Role of the Microbiome in Cancer and Therapy Efficacy: Focus on Lung Cancer.}, journal = {Anticancer research}, volume = {40}, number = {9}, pages = {4807-4818}, doi = {10.21873/anticanres.14484}, pmid = {32878769}, issn = {1791-7530}, mesh = {Anti-Bacterial Agents/therapeutic use ; Antineoplastic Agents/therapeutic use ; Bacteria/drug effects/isolation &amp; purification ; Carcinoma, Non-Small-Cell Lung/immunology/*microbiology/pathology/*therapy ; Humans ; Immunomodulation ; Lung Neoplasms/immunology/*microbiology/pathology/*therapy ; Microbiota/drug effects/*physiology ; Treatment Outcome ; }, abstract = {The microbiome is extremely important for human health; more recently its role in the context of cancer became clear. Microbial effects range from enhancing cancer immunity and cancer therapy efficacy, to promoting cancer progression and inhibiting treatment efficacy. These broad implications led researchers to investigate these specific interactions, as well as how modification of the microbiome can improve cancer survival and treatment efficacy. While these interactions are better established for cancers such as gastric cancer, they are far less understood in others. As non-small cell lung cancer (NSCLC) makes up the majority of lung cancer cases, and is among the top causes of cancer deaths worldwide, understanding the mechanisms by which the microbiome may impact progression and treatment is crucial to improve patient survival and treatment response. A literature review was conducted to reveal the crosslink between human microbiome and lung cancer. This includes immune priming, induction of pro- or anti-tumor response, and the local effects of intra-tumoral microbiota. Overall, this is a complex multifactorial relationship, and there are broad implications as to how this knowledge can improve cancer treatment. Solutions include manipulation of the microbiome using probiotics, bacterial vaccines and antibiotics. Bacteria biomarkers may also be used as a diagnostic tool.}, }
@article {pmid32872562, year = {2020}, author = {Ristori, MV and Mortera, SL and Marzano, V and Guerrera, S and Vernocchi, P and Ianiro, G and Gardini, S and Torre, G and Valeri, G and Vicari, S and Gasbarrini, A and Putignani, L}, title = {Proteomics and Metabolomics Approaches towards a Functional Insight onto AUTISM Spectrum Disorders: Phenotype Stratification and Biomarker Discovery.}, journal = {International journal of molecular sciences}, volume = {21}, number = {17}, pages = {}, pmid = {32872562}, issn = {1422-0067}, mesh = {Autism Spectrum Disorder/*diagnosis/metabolism ; Biomarkers/*analysis ; Humans ; *Metabolome ; Phenotype ; *Precision Medicine ; Proteome/*analysis ; }, abstract = {Autism spectrum disorders (ASDs) are neurodevelopmental disorders characterized by behavioral alterations and currently affect about 1% of children. Significant genetic factors and mechanisms underline the causation of ASD. Indeed, many affected individuals are diagnosed with chromosomal abnormalities, submicroscopic deletions or duplications, single-gene disorders or variants. However, a range of metabolic abnormalities has been highlighted in many patients, by identifying biofluid metabolome and proteome profiles potentially usable as ASD biomarkers. Indeed, next-generation sequencing and other omics platforms, including proteomics and metabolomics, have uncovered early age disease biomarkers which may lead to novel diagnostic tools and treatment targets that may vary from patient to patient depending on the specific genomic and other omics findings. The progressive identification of new proteins and metabolites acting as biomarker candidates, combined with patient genetic and clinical data and environmental factors, including microbiota, would bring us towards advanced clinical decision support systems (CDSSs) assisted by machine learning models for advanced ASD-personalized medicine. Herein, we will discuss novel computational solutions to evaluate new proteome and metabolome ASD biomarker candidates, in terms of their recurrence in the reviewed literature and laboratory medicine feasibility. Moreover, the way to exploit CDSS, performed by artificial intelligence, is presented as an effective tool to integrate omics data to electronic health/medical records (EHR/EMR), hopefully acting as added value in the near future for the clinical management of ASD.}, }
@article {pmid32872386, year = {2020}, author = {Neckovic, A and A H van Oorschot, R and Szkuta, B and Durdle, A}, title = {Challenges in Human Skin Microbial Profiling for Forensic Science: A Review.}, journal = {Genes}, volume = {11}, number = {9}, pages = {}, pmid = {32872386}, issn = {2073-4425}, mesh = {Bacteria/classification/*genetics/isolation &amp; purification ; *Bacterial Physiological Phenomena ; *Forensic Genetics ; *Forensic Sciences ; Humans ; *Microbiota ; Sequence Analysis, DNA ; Skin/*microbiology ; }, abstract = {The human microbiome is comprised of the microbes that live on and within an individual, as well as immediately surrounding them. Microbial profiling may have forensic utility in the identification or association of individuals with criminal activities, using microbial signatures derived from a personal microbiome. This review highlights some important aspects of recent studies, many of which have revealed issues involving the effect of contamination of microbial samples from both technical and environmental sources and their impacts on microbiome research and the potential forensic applications of microbial profiling. It is imperative that these challenges be discussed and evaluated within a forensic context to better understand the future directions and potential applications of microbial profiling for human identification. It is necessary that the limitations identified be resolved prior to the adoption of microbial profiling, or, at a minimum, acknowledged by those applying this new approach.}, }
@article {pmid32868914, year = {2021}, author = {Martino, C and Shenhav, L and Marotz, CA and Armstrong, G and McDonald, D and Vázquez-Baeza, Y and Morton, JT and Jiang, L and Dominguez-Bello, MG and Swafford, AD and Halperin, E and Knight, R}, title = {Context-aware dimensionality reduction deconvolutes gut microbial community dynamics.}, journal = {Nature biotechnology}, volume = {39}, number = {2}, pages = {165-168}, pmid = {32868914}, issn = {1546-1696}, support = {R01 MH122569/MH/NIMH NIH HHS/United States ; DP1 AT010885/AT/NCCIH NIH HHS/United States ; P30 DK120515/DK/NIDDK NIH HHS/United States ; R01 HL140976/HL/NHLBI NIH HHS/United States ; F31 DE028478/DE/NIDCR NIH HHS/United States ; UL1 TR001881/TR/NCATS NIH HHS/United States ; R56 MD013312/MD/NIMHD NIH HHS/United States ; R01 MH115979/MH/NIMH NIH HHS/United States ; R25 GM112625/GM/NIGMS NIH HHS/United States ; R01 HG010505/HG/NHGRI NIH HHS/United States ; }, mesh = {*Algorithms ; *Gastrointestinal Microbiome ; Humans ; Infant ; }, abstract = {The translational power of human microbiome studies is limited by high interindividual variation. We describe a dimensionality reduction tool, compositional tensor factorization (CTF), that incorporates information from the same host across multiple samples to reveal patterns driving differences in microbial composition across phenotypes. CTF identifies robust patterns in sparse compositional datasets, allowing for the detection of microbial changes associated with specific phenotypes that are reproducible across datasets.}, }
@article {pmid32868839, year = {2020}, author = {Kostopoulos, I and Elzinga, J and Ottman, N and Klievink, JT and Blijenberg, B and Aalvink, S and Boeren, S and Mank, M and Knol, J and de Vos, WM and Belzer, C}, title = {Akkermansia muciniphila uses human milk oligosaccharides to thrive in the early life conditions in vitro.}, journal = {Scientific reports}, volume = {10}, number = {1}, pages = {14330}, pmid = {32868839}, issn = {2045-2322}, mesh = {Akkermansia/enzymology/growth &amp; development ; Glycoside Hydrolases/metabolism ; Humans ; Milk, Human/*microbiology ; Mucus/metabolism ; Oligosaccharides/*metabolism ; }, abstract = {Akkermansia muciniphila is a well-studied anaerobic bacterium specialized in mucus degradation and associated with human health. Because of the structural resemblance of mucus glycans and free human milk oligosaccharides (HMOs), we studied the ability of A. muciniphila to utilize human milk oligosaccharides. We found that A. muciniphila was able to grow on human milk and degrade HMOs. Analyses of the proteome of A. muciniphila indicated that key-glycan degrading enzymes were expressed when the bacterium was grown on human milk. Our results display the functionality of the key-glycan degrading enzymes (α-L-fucosidases, β-galactosidases, exo-α-sialidases and β-acetylhexosaminidases) to degrade the HMO-structures 2'-FL, LNT, lactose, and LNT2. The hydrolysation of the host-derived glycan structures allows A. muciniphila to promote syntrophy with other beneficial bacteria, contributing in that way to a microbial ecological network in the gut. Thus, the capacity of A. muciniphila to utilize human milk will enable its survival in the early life intestine and colonization of the mucosal layer in early life, warranting later life mucosal and metabolic health.}, }
@article {pmid32865840, year = {2020}, author = {Ruokolainen, L and Fyhrquist, N and Laatikainen, T and Auvinen, P and Fortino, V and Scala, G and Jousilahti, P and Karisola, P and Vendelin, J and Karkman, A and Markelova, O and Mäkelä, MJ and Lehtimäki, S and Ndika, J and Ottman, N and Paalanen, L and Paulin, L and Vartiainen, E and von Hertzen, L and Greco, D and Haahtela, T and Alenius, H}, title = {Immune-microbiota interaction in Finnish and Russian Karelia young people with high and low allergy prevalence.}, journal = {Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology}, volume = {50}, number = {10}, pages = {1148-1158}, pmid = {32865840}, issn = {1365-2222}, mesh = {Adolescent ; Age Factors ; Female ; Finland/epidemiology ; Gene Regulatory Networks ; Genome-Wide Association Study ; *Health Status Disparities ; Host Microbial Interactions ; Humans ; Hypersensitivity/*epidemiology/immunology/microbiology/virology ; *Immunity, Innate/genetics ; Immunoglobulin E/blood ; Leukocytes, Mononuclear/immunology/microbiology/virology ; Male ; Microbiota/*immunology ; Nasal Mucosa/immunology/microbiology/virology ; Polymorphism, Single Nucleotide ; Prevalence ; Russia/epidemiology ; Skin/immunology/microbiology/virology ; Transcriptome ; Young Adult ; }, abstract = {BACKGROUND: After the Second World War, the population living in the Karelian region was strictly divided by the "iron curtain" between Finland and Russia. This resulted in different lifestyle, standard of living, and exposure to the environment. Allergic manifestations and sensitization to common allergens have been much more common on the Finnish compared to the Russian side.<br><br>OBJECTIVE: The remarkable allergy disparity in the Finnish and Russian Karelia calls for immunological explanations.<br><br>METHODS: Young people, aged 15-20 years, in the Finnish (n = 69) and Russian (n = 75) Karelia were studied. The impact of genetic variation on the phenotype was studied by a genome-wide association analysis. Differences in gene expression (transcriptome) were explored from the blood mononuclear cells (PBMC) and related to skin and nasal epithelium microbiota and sensitization.<br><br>RESULTS: The genotype differences between the Finnish and Russian populations did not explain the allergy gap. The network of gene expression and skin and nasal microbiota was richer and more diverse in the Russian subjects. When the function of 261 differentially expressed genes was explored, innate immunity pathways were suppressed among Russians compared to Finns. Differences in the gene expression paralleled the microbiota disparity. High Acinetobacter abundance in Russians correlated with suppression of innate immune response. High-total IgE was associated with enhanced anti-viral response in the Finnish but not in the Russian subjects.<br><br>Young populations living in the Finnish and Russian Karelia show marked differences in genome-wide gene expression and host contrasting skin and nasal epithelium microbiota. The rich gene-microbe network in Russians seems to result in a better-balanced innate immunity and associates with low allergy prevalence.}, }
@article {pmid32864214, year = {2020}, author = {Miossec, MJ and Valenzuela, SL and Pérez-Losada, M and Johnson, WE and Crandall, KA and Castro-Nallar, E}, title = {Evaluation of computational methods for human microbiome analysis using simulated data.}, journal = {PeerJ}, volume = {8}, number = {}, pages = {e9688}, pmid = {32864214}, issn = {2167-8359}, support = {UL1 TR001876/TR/NCATS NIH HHS/United States ; }, abstract = {BACKGROUND: Our understanding of the composition, function, and health implications of human microbiota has been advanced by high-throughput sequencing and the development of new genomic analyses. However, trade-offs among alternative strategies for the acquisition and analysis of sequence data remain understudied.<br><br>METHODS: We assessed eight popular taxonomic profiling pipelines; MetaPhlAn2, metaMix, PathoScope 2.0, Sigma, Kraken, ConStrains, Centrifuge and Taxator-tk, against a battery of metagenomic datasets simulated from real data. The metagenomic datasets were modeled on 426 complete or permanent draft genomes stored in the Human Oral Microbiome Database and were designed to simulate various experimental conditions, both in the design of a putative experiment; read length (75-1,000 bp reads), sequence depth (100K-10M), and in metagenomic composition; number of species present (10, 100, 426), species distribution. The sensitivity and specificity of each of the pipelines under various scenarios were measured. We also estimated the relative root mean square error and average relative error to assess the abundance estimates produced by different methods. Additional datasets were generated for five of the pipelines to simulate the presence within a metagenome of an unreferenced species, closely related to other referenced species. Additional datasets were also generated in order to measure computational time on datasets of ever-increasing sequencing depth (up to 6 &#xd7; 10[7]).<br><br>RESULTS: Testing of eight pipelines against 144 simulated metagenomic datasets initially produced 1,104 discrete results. Pipelines using a marker gene strategy; MetaPhlAn2 and ConStrains, were overall less sensitive, than other pipelines; with the notable exception of Taxator-tk. This difference in sensitivity was largely made up in terms of runtime, significantly lower than more sensitive pipelines that rely on whole-genome alignments such as PathoScope2.0. However, pipelines that used strategies to speed-up alignment between genomic references and metagenomic reads, such as kmerization, were able to combine both high sensitivity and low run time, as is the case with Kraken and Centrifuge. Absent species genomes in the database mostly led to assignment of reads to the most closely related species available in all pipelines. Our results therefore suggest that taxonomic profilers that use kmerization have largely superseded those that use gene markers, coupling low run times with high sensitivity and specificity. Taxonomic profilers using more time-consuming read reassignment, such as PathoScope 2.0, provided the most sensitive profiles under common metagenomic sequencing scenarios. All the results described and discussed in this paper can be visualized using the dedicated R Shiny application (https://github.com/microgenomics/HumanMicrobiomeAnalysis). All of our datasets, pipelines and results are made available through the GitHub repository for future benchmarking.}, }
@article {pmid32862522, year = {2020}, author = {Fidel, PL and Moyes, D and Samaranayake, L and Hagensee, ME}, title = {Interplay between oral immunity in HIV and the microbiome.}, journal = {Oral diseases}, volume = {26 Suppl 1}, number = {Suppl 1}, pages = {59-68}, pmid = {32862522}, issn = {1601-0825}, support = {R01 DE022815/DE/NIDCR NIH HHS/United States ; U54 GM104940/GM/NIGMS NIH HHS/United States ; }, mesh = {*HIV Infections/drug therapy/microbiology ; Humans ; India ; *Microbiota ; *Mouth Diseases/microbiology/virology ; }, abstract = {This Basic Science Workshop addressed the oral microbiome. At the 7th World Workshop on Oral Health &amp; Disease in HIV/AIDS in India in 2014, some aspects of the human microbiome were discussed, and research questions formulated. Since that time, there have been major advances in technology, which have stimulated a number of publications on many aspects of the human microbiome, including the oral cavity. This workshop aimed to summarize current understanding of the "normal" microbiome of the oral cavity compared to that during HIV infection, and how oral immune factors and other clinical variables alter or control the oral microbiome. An important question is whether successful treatment with anti-retroviral therapy, which leads to a significant drop in viral loads and immune reconstitution, is associated with any change or recovery of the oral microbiome. Additionally, the workshop addressed the issue of which parameters are most appropriate/correct to evaluate the oral microbiome and how clinically relevant are shifts/changes in the oral microbiome. The workshop evaluated current knowledge in five research areas related to five basic questions and identified further topics where further research is required.}, }
@article {pmid32853680, year = {2020}, author = {Bilen, M}, title = {Strategies and advancements in human microbiome description and the importance of culturomics.}, journal = {Microbial pathogenesis}, volume = {149}, number = {}, pages = {104460}, doi = {10.1016/j.micpath.2020.104460}, pmid = {32853680}, issn = {1096-1208}, mesh = {Bacteria/genetics ; *Gastrointestinal Microbiome ; Humans ; *Microbiota ; }, abstract = {The human microbiota gained a big interest among the scientific community with numerous studies being performed to better understand its role in health and diseases. Even with all the success achieved in studying the bacterial populations at the different body sites and its interaction among each other and with the host, some links remain missing and might have therapeutic benefits. In this review, we summarize the main means used for bacterial identification, human microbiota description and the role of culturomics in leading the way towards the development of new bacterio-therapeutic approaches.}, }
@article {pmid32852821, year = {2020}, author = {Lahtinen, P and Jalanka, J and Hartikainen, A and Mattila, E and Hillilä, M and Punkkinen, J and Koskenpato, J and Anttila, VJ and Tillonen, J and Satokari, R and Arkkila, P}, title = {Letter: faecal microbiota transplantation for irritable bowel syndrome-room for improvement. Authors' reply.}, journal = {Alimentary pharmacology &amp; therapeutics}, volume = {52}, number = {5}, pages = {925-926}, doi = {10.1111/apt.15942}, pmid = {32852821}, issn = {1365-2036}, mesh = {Colonoscopy ; Fecal Microbiota Transplantation ; Humans ; *Irritable Bowel Syndrome/therapy ; }, }
@article {pmid32852581, year = {2020}, author = {Griffiths, JC and De Vries, J and McBurney, MI and Wopereis, S and Serttas, S and Marsman, DS}, title = {Measuring health promotion: translating science into policy.}, journal = {European journal of nutrition}, volume = {59}, number = {Suppl 2}, pages = {11-23}, pmid = {32852581}, issn = {1436-6215}, mesh = {*Health Promotion ; Humans ; Life Style ; Longevity ; Policy ; *Quality of Life ; }, abstract = {Commonly, it is the end of life when our health is deteriorating, that many will make drastic lifestyle changes to improve their quality of life. However, it is increasingly recognized that bringing good health-promoting behaviors into practice as early in life as possible has the most significant impact across the maximal healthspan. The WHO has brought clarity to health promotion over the last fifteen years, always centering on language relating to a process of enabling people to increase control over, and to improve, their physical, mental and social health. A good healthspan is not just freedom from morbidity and mortality, it is that joie de vivre ("joy of living") that should accompany every day of our lifespan. Therefore, health promotion includes not only the health sector, but also needs individual commitment to achieve that target of a healthspan aligned with the lifespan. This paper explores health promotion and health literacy, and how to design appropriate nutritional studies to characterize contributors to a positive health outcome, the role the human microbiome plays in promoting health and addressing and alleviating morbidity and diseases, and finally how to characterize phenotypic flexibility and a physiologic resilience that we must maintain as our structural and functional systems are bombarded with the insults and perturbations of life.}, }
@article {pmid32851161, year = {2020}, author = {Khazaei, T and Williams, RL and Bogatyrev, SR and Doyle, JC and Henry, CS and Ismagilov, RF}, title = {Metabolic multistability and hysteresis in a model aerobe-anaerobe microbiome community.}, journal = {Science advances}, volume = {6}, number = {33}, pages = {eaba0353}, pmid = {32851161}, issn = {2375-2548}, mesh = {Humans ; *Microbiota ; Nutrients ; Oxygen ; }, abstract = {Major changes in the microbiome are associated with health and disease. Some microbiome states persist despite seemingly unfavorable conditions, such as the proliferation of aerobe-anaerobe communities in oxygen-exposed environments in wound infections or small intestinal bacterial overgrowth. Mechanisms underlying transitions into and persistence of these states remain unclear. Using two microbial taxa relevant to the human microbiome, we combine genome-scale mathematical modeling, bioreactor experiments, transcriptomics, and dynamical systems theory to show that multistability and hysteresis (MSH) is a mechanism describing the shift from an aerobe-dominated state to a resilient, paradoxically persistent aerobe-anaerobe state. We examine the impact of changing oxygen and nutrient regimes and identify changes in metabolism and gene expression that lead to MSH and associated multi-stable states. In such systems, conceptual causation-correlation connections break and MSH must be used for analysis. Using MSH to analyze microbiome dynamics will improve our conceptual understanding of stability of microbiome states and transitions between states.}, }
@article {pmid32850496, year = {2020}, author = {Wagner Mackenzie, B and West, AG and Waite, DW and Lux, CA and Douglas, RG and Taylor, MW and Biswas, K}, title = {A Novel Description of the Human Sinus Archaeome During Health and Chronic Rhinosinusitis.}, journal = {Frontiers in cellular and infection microbiology}, volume = {10}, number = {}, pages = {398}, pmid = {32850496}, issn = {2235-2988}, mesh = {Archaea/genetics ; Cross-Sectional Studies ; Humans ; *Microbiota ; Phylogeny ; RNA, Ribosomal, 16S/genetics ; *Sinusitis ; }, abstract = {Human microbiome studies remain focused on bacteria, as they comprise the dominant component of the microbiota. Recent advances in sequencing technology and optimization of amplicon sequencing protocols have allowed the description of other members of the microbiome, including eukaryotes (fungi) and, most recently, archaea. There are no known human-associated archaeal pathogens. Their diversity and contribution to health and chronic respiratory diseases, such as chronic rhinosinusitis (CRS), are unknown. Patients with CRS suffer from long-term sinus infections, and while the microbiota is hypothesized to play a role in its pathogenesis, the exact mechanism is poorly understood. In this cross-sectional study, we applied a recently optimized protocol to describe the prevalence, diversity and abundance of archaea in swab samples from the middle meatus of 60 individuals with and without CRS. A nested PCR approach was used to amplify the archaeal 16S rRNA gene for sequencing, and bacterial and archaeal load (also based on 16S rRNA genes) were estimated using Droplet Digital™ PCR (ddPCR). A total of 16 archaeal amplicon sequence variants (ASVs) from the phyla Euryarchaeota and Thaumarchaeota were identified. Archaeal ASVs were detected in 7/60 individuals, independent of disease state, whereas bacterial ASVs were detected in 60/60. Bacteria were also significantly more abundant than archaea. The ddPCR method was more sensitive than amplicon sequencing at detecting archaeal DNA in samples. Phylogenetic trees were constructed to visualize the evolutionary relationships between archaeal ASVs, isolates and clones. ASVs were placed into phylogenetic clades containing an apparent paucity of human-associated reference sequences, revealing how little studied the human archaeome is. This is the largest study to date to examine the human respiratory-associated archaeome, and provides the first insights into the prevalence, diversity and abundance of archaea in the human sinuses.}, }
@article {pmid32845143, year = {2020}, author = {Bushin, LB and Covington, BC and Rued, BE and Federle, MJ and Seyedsayamdost, MR}, title = {Discovery and Biosynthesis of Streptosactin, a Sactipeptide with an Alternative Topology Encoded by Commensal Bacteria in the Human Microbiome.}, journal = {Journal of the American Chemical Society}, volume = {142}, number = {38}, pages = {16265-16275}, doi = {10.1021/jacs.0c05546}, pmid = {32845143}, issn = {1520-5126}, mesh = {Humans ; *Microbiota ; Molecular Structure ; Pore Forming Cytotoxic Proteins/*biosynthesis/*chemistry/isolation &amp; purification ; Streptococcus thermophilus/*chemistry/metabolism ; }, abstract = {Mammalian microbiomes encode thousands of biosynthetic gene clusters (BGCs) and represent a new frontier in natural product research. We recently found an abundance of quorum sensing-regulated BGCs in mammalian microbiome streptococci that code for ribosomally synthesized and post-translationally modified peptides (RiPPs) and contain one or more radical S-adenosylmethionine (RaS) enzymes, a versatile superfamily known to catalyze some of the most unusual reactions in biology. In the current work, we target a widespread group of streptococcal RiPP BGCs and elucidate both the reaction carried out by its encoded RaS enzyme and identify its peptide natural product, which we name streptosactin. Streptosactin is the first sactipeptide identified from Streptococcus spp.; it contains two sequential four amino acid sactionine macrocycles, an unusual topology for this compound family. Bioactivity assays reveal potent but narrow-spectrum activity against the producing strain and its closest relatives that carry the same BGC, suggesting streptosactin may be a long-suspected fratricidal agent of Streptococcus thermophilus. Our results highlight mammalian streptococci as a rich source of unusual enzymatic chemistries and bioactive natural products.}, }
@article {pmid32843932, year = {2020}, author = {Li, WZ and Stirling, K and Yang, JJ and Zhang, L}, title = {Gut microbiota and diabetes: From correlation to causality and mechanism.}, journal = {World journal of diabetes}, volume = {11}, number = {7}, pages = {293-308}, pmid = {32843932}, issn = {1948-9358}, abstract = {In this review, we summarize the recent microbiome studies related to diabetes disease and discuss the key findings that show the early emerging potential causal roles for diabetes. On a global scale, diabetes causes a significant negative impact to the health status of human populations. This review covers type 1 diabetes and type 2 diabetes. We examine promising studies which lead to a better understanding of the potential mechanism of microbiota in diabetes diseases. It appears that the human oral and gut microbiota are deeply interdigitated with diabetes. It is that simple. Recent studies of the human microbiome are capturing the attention of scientists and healthcare practitioners worldwide by focusing on the interplay of gut microbiome and diabetes. These studies focus on the role and the potential impact of intestinal microflora in diabetes. We paint a clear picture of how strongly microbes are linked and associated, both positively and negatively, with the fundamental and essential parts of diabetes in humans. The microflora seems to have an endless capacity to impact and transform diabetes. We conclude that there is clear and growing evidence of a close relationship between the microbiota and diabetes and this is worthy of future investments and research efforts.}, }
@article {pmid32842596, year = {2020}, author = {Jalanka, J and Cheng, J and Hiippala, K and Ritari, J and Salojärvi, J and Ruuska, T and Kalliomäki, M and Satokari, R}, title = {Colonic Mucosal Microbiota and Association of Bacterial Taxa with the Expression of Host Antimicrobial Peptides in Pediatric Ulcerative Colitis.}, journal = {International journal of molecular sciences}, volume = {21}, number = {17}, pages = {}, pmid = {32842596}, issn = {1422-0067}, support = {323156//Academy of Finland/ ; 316338//Academy of Finland/ ; Senior Research Fellow//Sigrid Jus&#xe9;liuksen S&#xe4;&#xe4;ti&#xf6;/ ; A three-year grant//Helsingin Yliopisto/ ; 160048//Lastentautien Tutkimuss&#xe4;&#xe4;ti&#xf6;/ ; EVO 13004//Varsinais-Suomen Sairaanhoitopiiri/ ; }, mesh = {Adolescent ; Bacteroidetes/genetics ; Case-Control Studies ; Child ; Child, Preschool ; Colitis, Ulcerative/*microbiology ; DNA, Ribosomal ; Enterobacteriaceae/genetics ; Finland ; Gastrointestinal Microbiome/genetics/*physiology ; Gene Expression ; Humans ; Inflammatory Bowel Diseases/microbiology ; Intestinal Mucosa/pathology/*physiology ; Lipocalin-2/genetics ; Pancreatitis-Associated Proteins/genetics ; Pore Forming Cytotoxic Proteins/*genetics ; beta-Defensins/genetics ; }, abstract = {Inflammatory bowel diseases (IBD), ulcerative colitis (UC) and Crohn's disease (CD), are chronic debilitating disorders of unknown etiology. Over 200 genetic risk loci are associated with IBD, highlighting a key role for immunological and epithelial barrier functions. Environmental factors account for the growing incidence of IBD, and microbiota are considered as an important contributor. Microbiota dysbiosis can lead to a loss of tolerogenic immune effects and initiate or exacerbate inflammation. We aimed to study colonic mucosal microbiota and the expression of selected host genes in pediatric UC. We used high-throughput 16S rDNA sequencing to profile microbiota in colonic biopsies of pediatric UC patients (n = 26) and non-IBD controls (n = 27). The expression of 13 genes, including five for antimicrobial peptides, in parallel biopsies was assessed with qRT-PCR. The composition of microbiota between UC and non-IBD differed significantly (PCoA, p = 0.001). UC children had a decrease in Bacteroidetes and an increase in several family-level taxa including Peptostreptococcaceae and Enterobacteriaceae, which correlated negatively with the expression of antimicrobial peptides REG3G and DEFB1, respectively. Enterobacteriaceae correlated positively with the expression siderophore binding protein LCN2 and Betaproteobacteria negatively with DEFB4A expression. The results indicate that reciprocal interaction of epithelial microbiota and defense mechanisms play a role in UC.}, }
@article {pmid32841200, year = {2020}, author = {Nurgaziyev, M and Sergazy, S and Chulenbayeva, L and Nurgozhina, A and Gulyayev, A and Kozhakhmetov, S and Kartbayeva, G and Kushugulova, A}, title = {THE EFFECTS OF ANTIBIOTICS ON THE GUT MICROBIOME AND THE IMMUNE SYSTEM (Review).}, journal = {Georgian medical news}, volume = {}, number = {303}, pages = {167-173}, pmid = {32841200}, issn = {1512-0112}, mesh = {Adult ; Anti-Bacterial Agents/therapeutic use ; Child ; Drug Resistance, Microbial/drug effects ; *Gastrointestinal Microbiome ; Humans ; Immune System/drug effects ; *Microbiota ; }, abstract = {Antibiotic resistance and its impact on human microbiome remains a global public health concern. Studies have shown that treatment with antibiotics leads to dramatic changes in composition and function of gut microbiome. This review focuses on the association between antibiotics use and its impact on gut microbiome of adults and children, gut microbiota metabolic interactions and presents the current understanding of the link between human gut microbiome and immune system.}, }
@article {pmid32834004, year = {2020}, author = {Dong, M and Li, L and Chen, M and Kusalik, A and Xu, W}, title = {Predictive analysis methods for human microbiome data with application to Parkinson's disease.}, journal = {PloS one}, volume = {15}, number = {8}, pages = {e0237779}, pmid = {32834004}, issn = {1932-6203}, mesh = {Adult ; Age Factors ; Aged ; Aged, 80 and over ; Bacteria/*classification/genetics/isolation &amp; purification ; Cohort Studies ; Computer Simulation ; DNA, Bacterial/isolation &amp; purification ; *Data Interpretation, Statistical ; Datasets as Topic ; Female ; Gastrointestinal Microbiome/*genetics ; Humans ; Logistic Models ; Male ; Middle Aged ; *Models, Biological ; Parkinson Disease/*diagnosis/microbiology ; Predictive Value of Tests ; Prognosis ; RNA, Ribosomal, 16S/genetics ; Sex Factors ; }, abstract = {Microbiome data consists of operational taxonomic unit (OTU) counts characterized by zero-inflation, over-dispersion, and grouping structure among samples. Currently, statistical testing methods are commonly performed to identify OTUs that are associated with a phenotype. The limitations of statistical testing methods include that the validity of p-values/q-values depend sensitively on the correctness of models and that the statistical significance does not necessarily imply predictivity. Predictive analysis using methods such as LASSO is an alternative approach for identifying associated OTUs and for measuring the predictability of the phenotype variable with OTUs and other covariate variables. We investigate three strategies of performing predictive analysis: (1) LASSO: fitting a LASSO multinomial logistic regression model to all OTU counts with specific transformation; (2) screening+GLM: screening OTUs with q-values returned by fitting a GLMM to each OTU, then fitting a GLM model using a subset of selected OTUs; (3) screening+LASSO: fitting a LASSO to a subset of OTUs selected with GLMM. We have conducted empirical studies using three simulation datasets generated using Dirichlet-multinomial models and a real gut microbiome data related to Parkinson's disease to investigate the performance of the three strategies for predictive analysis. Our simulation studies show that the predictive performance of LASSO with appropriate variable transformation works remarkably well on zero-inflated data. Our results of real data analysis show that Parkinson's disease can be predicted based on selected OTUs after the binary transformation, age, and sex with high accuracy (Error Rate = 0.199, AUC = 0.872, AUPRC = 0.912). These results provide strong evidences of the relationship between Parkinson's disease and the gut microbiome.}, }
@article {pmid32833508, year = {2020}, author = {Kurian, SM and Gordon, S and Barrick, B and Dadlani, MN and Fanelli, B and Cornell, JB and Head, SR and Marsh, CL and Case, J}, title = {Feasibility and Comparison Study of Fecal Sample Collection Methods in Healthy Volunteers and Solid Organ Transplant Recipients Using 16S rRNA and Metagenomics Approaches.}, journal = {Biopreservation and biobanking}, volume = {18}, number = {5}, pages = {425-440}, doi = {10.1089/bio.2020.0032}, pmid = {32833508}, issn = {1947-5543}, mesh = {Feasibility Studies ; Feces ; Healthy Volunteers ; Humans ; *Metagenomics ; *Organ Transplantation ; Pilot Projects ; Prospective Studies ; RNA, Ribosomal, 16S ; }, abstract = {The human microbiome encompasses a variety of microorganisms that change dynamically and are in close contact with the body. The microbiome influences health and homeostasis, as well as the immune system, and any significant change in this equilibrium (dysbiosis) triggers both acute and chronic health conditions. Microbiome research has surged, in part, due to advanced sequencing technologies enabling rapid, accurate, and cost-effective identification of the microbiome. A major prerequisite for stool sample collection to study the gut microbiome in longitudinal prospective studies requires standardized protocols that can be easily replicated. However, there are still significant bottlenecks to stool specimen collection that contribute to low patient retention rates in microbiome studies. These barriers are further exacerbated in solid organ transplant recipients where diarrhea is estimated to occur in up to half the patient population. We sought to test two relatively easy sample collection methods (fecal swab and wipes) and compare them to the more cumbersome "gold" standard collection method (scoop) using two different sequencing technologies (16S ribosomal RNA sequencing and shotgun metagenomics). Our comparison of the collection methods shows that both the swabs and the wipes are comparable to the scoop method in terms of bacterial abundance and diversity. The swabs, however, were closer in representation to the scoop and were easier to collect and process compared to the wipes. Potential contamination of the swab and the wipe samples by abundant skin commensals was low in our analysis. Comparison of the two sequencing technologies showed that they were complementary, and that 16S sequencing provided enough coverage to detect and differentiate between bacterial species identified in the collected samples. Our pilot study demonstrates that alternative collection methods for stool sampling are a viable option in clinical applications, such as organ transplant studies. The use of these methods may result in better patient retention recruitment rates in serial microbiome studies.}, }
@article {pmid32825532, year = {2020}, author = {Nava Lara, RA and Beltrán, JA and Brizuela, CA and Del Rio, G}, title = {Relevant Features of Polypharmacologic Human-Target Antimicrobials Discovered by Machine-Learning Techniques.}, journal = {Pharmaceuticals (Basel, Switzerland)}, volume = {13}, number = {9}, pages = {}, pmid = {32825532}, issn = {1424-8247}, support = {CB252316//Consejo Nacional de Ciencia y Tecnolog&#xed;a/ ; IN208817//Direcci&#xf3;n General de Asuntos del Personal Acad&#xe9;mico, Universidad Nacional Aut&#xf3;noma de M&#xe9;xico/ ; }, abstract = {Polypharmacologic human-targeted antimicrobials (polyHAM) are potentially useful in the treatment of complex human diseases where the microbiome is important (e.g., diabetes, hypertension). We previously reported a machine-learning approach to identify polyHAM from FDA-approved human targeted drugs using a heterologous approach (training with peptides and non-peptide compounds). Here we discover that polyHAM are more likely to be found among antimicrobials displaying a broad-spectrum antibiotic activity and that topological, but not chemical features, are most informative to classify this activity. A heterologous machine-learning approach was trained with broad-spectrum antimicrobials and tested with human metabolites; these metabolites were labeled as antimicrobials or non-antimicrobials based on a naïve text-mining approach. Human metabolites are not commonly recognized as antimicrobials yet circulate in the human body where microbes are found and our heterologous model was able to classify those with antimicrobial activity. These results provide the basis to develop applications aimed to design human diets that purposely alter metabolic compounds proportions as a way to control human microbiome.}, }
@article {pmid32822862, year = {2021}, author = {Sharma, AK}, title = {Special Issue: Mining human microbiome bringing newer paradigms to anticancer therapeutics.}, journal = {Seminars in cancer biology}, volume = {70}, number = {}, pages = {1-2}, doi = {10.1016/j.semcancer.2020.08.008}, pmid = {32822862}, issn = {1096-3650}, mesh = {Antineoplastic Agents/*therapeutic use ; *Gastrointestinal Microbiome ; *Genome, Microbial ; Humans ; *Metagenome ; *Microbiota ; Neoplasms/genetics/microbiology/*therapy ; }, }
@article {pmid32821643, year = {2020}, author = {Cafiero, C and Re, A and Pisconti, S and Trombetti, M and Perri, M and Colosimo, M and D'Amato, G and Gallelli, L and Cannataro, R and Molinario, C and Fazio, A and Caroleo, MC and Cione, E}, title = {Dysbiosis in intestinal microbiome linked to fecal blood determined by direct hybridization.}, journal = {3 Biotech}, volume = {10}, number = {8}, pages = {358}, pmid = {32821643}, issn = {2190-572X}, abstract = {The important physiological and pathophysiological roles of intestinal human microbiome (HMB) in human health have been emerging, owing to the access to molecular biology techniques. Herein we evaluated, for the first time, the intestinal HMB through direct hybridization approach using n-counter flex DX technology which bypasses the amplification procedure currently applied by other technologies to study the human microbiome. To this purpose, a clinical study was carried out on fecal samples, recruiting both healthy volunteers (N-FOB) and subjects positive for occult blood (P-FOB). A relevant custom panel of 79 16S rRNA target gene was engineered and 32 of them displayed a variation between the two clusters of subjects. Our findings revealed that bacteria belonging to Proteobacteria have higher distribution in P-FOB describing dysbiosis. Similarly, Bacteroidetes and Firmicutes phylum display high distribution in P-FOB. Of interest, the presence of Clostridium difficile that belongs to Firmicutes phylum displayed about 70% of low presence in N-FOB compared to P-FOB subjects. Only one bacterium belonging to the Actinobacteria phylum, the Bifidobacterium bifidum, was present.}, }
@article {pmid32817490, year = {2020}, author = {Britton, GJ and Contijoch, EJ and Spindler, MP and Aggarwala, V and Dogan, B and Bongers, G and San Mateo, L and Baltus, A and Das, A and Gevers, D and Borody, TJ and Kaakoush, NO and Kamm, MA and Mitchell, H and Paramsothy, S and Clemente, JC and Colombel, JF and Simpson, KW and Dubinsky, MC and Grinspan, A and Faith, JJ}, title = {Defined microbiota transplant restores Th17/RORγt[+] regulatory T cell balance in mice colonized with inflammatory bowel disease microbiotas.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {117}, number = {35}, pages = {21536-21545}, pmid = {32817490}, issn = {1091-6490}, support = {R01 DK112296/DK/NIDDK NIH HHS/United States ; S10 OD026880/OD/NIH HHS/United States ; R01 DK112978/DK/NIDDK NIH HHS/United States ; R01 DK124133/DK/NIDDK NIH HHS/United States ; R01 GM108505/GM/NIGMS NIH HHS/United States ; P30 CA016087/CA/NCI NIH HHS/United States ; R01 DK123749/DK/NIDDK NIH HHS/United States ; F31 DK112679/DK/NIDDK NIH HHS/United States ; T32 AI078892/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Colitis/prevention &amp; control ; Colon/microbiology ; Crohn Disease/metabolism/microbiology ; Cytokines/immunology ; Disease Models, Animal ; *Fecal Microbiota Transplantation ; Feces/microbiology ; Female ; Gastrointestinal Microbiome/immunology ; Humans ; Inflammatory Bowel Diseases/immunology/*microbiology ; Male ; Mice ; Mice, Inbred C57BL ; Nuclear Receptor Subfamily 1, Group F, Member 3/*immunology ; T-Lymphocytes, Regulatory/*immunology/microbiology ; Th17 Cells/*immunology/microbiology ; }, abstract = {The building evidence for the contribution of microbiota to human disease has spurred an effort to develop therapies that target the gut microbiota. This is particularly evident in inflammatory bowel diseases (IBDs), where clinical trials of fecal microbiota transplantation have shown some efficacy. To aid the development of novel microbiota-targeted therapies and to better understand the biology underpinning such treatments, we have used gnotobiotic mice to model microbiota manipulations in the context of microbiotas from humans with inflammatory bowel disease. Mice colonized with IBD donor-derived microbiotas exhibit a stereotypical set of phenotypes, characterized by abundant mucosal Th17 cells, a deficit in the tolerogenic RORγt[+] regulatory T (Treg) cell subset, and susceptibility to disease in colitis models. Transplanting healthy donor-derived microbiotas into mice colonized with human IBD microbiotas led to induction of RORγt[+] Treg cells, which was associated with an increase in the density of the microbiotas following transplant. Microbiota transplant reduced gut Th17 cells in mice colonized with a microbiota from a donor with Crohn's disease. By culturing strains from this microbiota and screening them in vivo, we identified a specific strain that potently induces Th17 cells. Microbiota transplants reduced the relative abundance of this strain in the gut microbiota, which was correlated with a reduction in Th17 cells and protection from colitis.}, }
@article {pmid32816985, year = {2020}, author = {Lamont, EI and Hendrickson, EL and McLean, JS and He, X and Bor, B}, title = {Complete Genome Sequence of Strain BB001, a Novel Epibiont Bacterium from the Candidate Phylum Saccharibacteria (TM7).}, journal = {Microbiology resource announcements}, volume = {9}, number = {34}, pages = {}, pmid = {32816985}, issn = {2576-098X}, support = {F32 DE025548/DE/NIDCR NIH HHS/United States ; K99 DE027719/DE/NIDCR NIH HHS/United States ; R01 DE020102/DE/NIDCR NIH HHS/United States ; R00 DE027719/DE/NIDCR NIH HHS/United States ; R01 DE023810/DE/NIDCR NIH HHS/United States ; R01 DE026186/DE/NIDCR NIH HHS/United States ; }, abstract = {Strain BB001 is cultivated from the human oral cavity on its basibiont bacterial host Actinomyces sp. It is an ultrasmall bacterium with a reduced genome that grows obligately on its bacterial host. BB001 is the first member of human microbiome taxon 957.}, }
@article {pmid32816830, year = {2020}, author = {Yan, R and Murphy, M and Genoni, A and Marlow, E and Dunican, IC and Lo, J and Andrew, L and Devine, A and Christophersen, CT}, title = {Does Fibre-fix provided to people with irritable bowel syndrome who are consuming a low FODMAP diet improve their gut health, gut microbiome, sleep and mental health? A double-blinded, randomised controlled trial.}, journal = {BMJ open gastroenterology}, volume = {7}, number = {1}, pages = {}, pmid = {32816830}, issn = {2054-4774}, mesh = {Adult ; Aged ; Case-Control Studies ; Dietary Fiber/administration &amp; dosage/*adverse effects/therapeutic use ; Disaccharides/administration &amp; dosage/adverse effects ; Double-Blind Method ; Fatty Acids, Volatile ; Feces/microbiology ; Female ; Fermentation/*physiology ; Gastrointestinal Diseases/*diet therapy/microbiology ; Gastrointestinal Microbiome/*immunology/physiology ; Humans ; Irritable Bowel Syndrome/blood/diagnosis/*diet therapy/psychology ; Male ; Mental Health/statistics &amp; numerical data ; Middle Aged ; Monosaccharides/administration &amp; dosage/adverse effects ; Oligosaccharides/administration &amp; dosage/adverse effects ; Outcome Assessment, Health Care ; Polymers/administration &amp; dosage/adverse effects ; Quality of Life ; Sleep/physiology ; Surveys and Questionnaires/statistics &amp; numerical data ; }, abstract = {INTRODUCTION: A diet low in fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAP) is an effective way to reduce gut symptoms in people with irritable bowel syndrome (IBS). This diet reduces the intake of fermentable fibres, leading to changes of the gut microbiota and insufficient fermentation in the large bowel, resulting in reduced production of short-chain fatty acids (SCFAs), such as butyrate, which has unfavourable implications for gut health, sleep and mental health. This study will examine the effect of Fibre-fix, a supplement containing a mix of dietary fibres, on the human gut microbiome composition, fermentative capacity, sleep, quality of life (QOL) and mental health of people with IBS who consume a low FODMAP diet (LFD).<br><br>METHODS AND ANALYSIS: A randomised, double-blind, placebo-controlled, study design is proposed to examine whether Fibre-fix added to an existing LFD may help modulate gastrointestinal function, improve markers of sleep, mental health and promote QOL in patients with IBS. Participants will provide stool and blood samples, daily bowel symptoms diaries and 3-day diet records. Additionally, they will complete validated questionnaires relating to FODMAP intake, sleep, mental health and QOL before and after a 3-week intervention. Gut health will be assessed via faecal microbiome composition, faecal pH and SCFA levels. Alteration of sleep will be recorded using an actigraphy device worn by all participants over the whole study. Multivariate analysis will be used to examine the gut microbiome and repeated measures Analysis of variance (ANOVA) will be used for dependent variables from questionnaires related to bowel symptoms, stool type, sleep, mental health and QOL to assess the differences between intervention and control groups after adjustment for confounding variables.<br><br>ETHICS AND DISSEMINATION: Ethics approval was obtained from the Human Research Ethics Committee of Edith Cowan University (2019-00619-YAN). Results will be disseminated in peer-review journal publications, and conference presentations. Participants will be provided with a summary of findings once the study is completed. If Fibre-fix is shown to result in favourable changes in gut microbial composition, SCFA production, sleep and mental well-being without exacerbating symptoms, this will provide additional dietary management options for those with IBS following an LFD.<br><br>TRIAL REGISTRATION NUMBER: ACTRN12620000032954.}, }
@article {pmid32814564, year = {2020}, author = {Vidanaarachchi, R and Shaw, M and Tang, SL and Halgamuge, S}, title = {IMPARO: inferring microbial interactions through parameter optimisation.}, journal = {BMC molecular and cell biology}, volume = {21}, number = {Suppl 1}, pages = {34}, pmid = {32814564}, issn = {2661-8850}, mesh = {Algorithms ; Bacteria/*metabolism ; Data Accuracy ; Feces/microbiology ; Female ; *Gastrointestinal Microbiome ; Healthy Volunteers ; Humans ; Male ; Microbial Interactions/*physiology ; *Models, Biological ; }, abstract = {BACKGROUND: Microbial Interaction Networks (MINs) provide important information for understanding bacterial communities. MINs can be inferred by examining microbial abundance profiles. Abundance profiles are often interpreted with the Lotka Volterra model in research. However existing research fails to consider a biologically meaningful underlying mathematical model for MINs or to address the possibility of multiple solutions.<br><br>RESULTS: In this paper we present IMPARO, a method for inferring microbial interactions through parameter optimisation. We use biologically meaningful models for both the abundance profile, as well as the MIN. We show how multiple MINs could be inferred with similar reconstructed abundance profile accuracy, and argue that a unique solution is not always satisfactory. Using our method, we successfully inferred clear interactions in the gut microbiome which have been previously observed in in-vitro experiments.<br><br>CONCLUSIONS: IMPARO was used to successfully infer microbial interactions in human microbiome samples as well as in a varied set of simulated data. The work also highlights the importance of considering multiple solutions for MINs.}, }
@article {pmid32806740, year = {2020}, author = {Kari, OK and Tavakoli, S and Parkkila, P and Baan, S and Savolainen, R and Ruoslahti, T and Johansson, NG and Ndika, J and Alenius, H and Viitala, T and Urtti, A and Lajunen, T}, title = {Light-Activated Liposomes Coated with Hyaluronic Acid as a Potential Drug Delivery System.}, journal = {Pharmaceutics}, volume = {12}, number = {8}, pages = {}, pmid = {32806740}, issn = {1999-4923}, support = {311122//Academy of Finland/ ; 317336//Academy of Finland/ ; 4208/31/2015//Business Finland/ ; 676137//Horizon 2020/ ; 9-8214-9//Orionin Tutkimuss&#xe4;&#xe4;ti&#xf6;/ ; 0//Phospholipid Research Center/ ; 0//Emil Aaltosen S&#xe4;&#xe4;ti&#xf6;/ ; 0//Instrumentariumin Tiedes&#xe4;&#xe4;ti&#xf6;/ ; 0//Mary och Georg C. Ehrnrooths Stiftelse/ ; 0//Evald ja Hilda Nissin S&#xe4;&#xe4;ti&#xf6;/ ; 0//Inkeri and Mauri V&#xe4;nsk&#xe4; Foundation/ ; 0//Paulon S&#xe4;&#xe4;ti&#xf6;/ ; 0//P&#xe4;ivikki ja Sakari Sohlbergin S&#xe4;&#xe4;ti&#xf6;/ ; }, abstract = {Light-activated liposomes permit site and time-specific drug delivery to ocular and systemic targets. We combined a light activation technology based on indocyanine green with a hyaluronic acid (HA) coating by synthesizing HA-lipid conjugates. HA is an endogenous vitreal polysaccharide and a potential targeting moiety to cluster of differentiation 44 (CD44)-expressing cells. Light-activated drug release from 100 nm HA-coated liposomes was functional in buffer, plasma, and vitreous samples. The HA-coating improved stability in plasma compared to polyethylene glycol (PEG)-coated liposomes. Liposomal protein coronas on HA- and PEG-coated liposomes after dynamic exposure to undiluted human plasma and porcine vitreous samples were hydrophilic and negatively charged, thicker in plasma (~5 nm hard, ~10 nm soft coronas) than in vitreous (~2 nm hard, ~3 nm soft coronas) samples. Their compositions were dependent on liposome formulation and surface charge in plasma but not in vitreous samples. Compared to the PEG coating, the HA-coated liposomes bound more proteins in vitreous samples and enriched proteins related to collagen interactions, possibly explaining their slightly reduced vitreal mobility. The properties of the most abundant proteins did not correlate with liposome size or charge, but included proteins with surfactant and immune system functions in plasma and vitreous samples. The HA-coated light-activated liposomes are a functional and promising alternative for intravenous and ocular drug delivery.}, }
@article {pmid32806589, year = {2020}, author = {Sun, Y and Kong, L and Wu, G and Cao, B and Pang, X and Deng, Z and Dedon, PC and Zhang, C and You, D}, title = {DNA Phosphorothioate Modifications Are Widely Distributed in the Human Microbiome.}, journal = {Biomolecules}, volume = {10}, number = {8}, pages = {}, pmid = {32806589}, issn = {2218-273X}, support = {31630002//National Natural Science Foundation of China/International ; }, mesh = {Bacteria/*classification/genetics/isolation &amp; purification ; Bacterial Proteins/*genetics ; Computational Biology/*methods ; DNA, Bacterial/*chemistry ; Databases, Genetic ; Feces/chemistry ; Gastrointestinal Tract/microbiology ; Humans ; Mass Spectrometry ; Microbiota ; Phosphates/*chemistry ; Phylogeny ; Sequence Alignment ; }, abstract = {The DNA phosphorothioate (PT) modification existing in many prokaryotes, including bacterial pathogens and commensals, confers multiple characteristics, including restricting gene transfer, influencing the global transcriptional response, and reducing fitness during exposure to chemical mediators of inflammation. While PT-containing bacteria have been investigated in a variety of environments, they have not been studied in the human microbiome. Here, we investigated the distribution of PT-harboring strains and verified their existence in the human microbiome. We found over 2000 PT gene-containing strains distributed in different body sites, especially in the gastrointestinal tract. PT-modifying genes are preferentially distributed within several genera, including Pseudomonas, Clostridioides, and Escherichia, with phylogenic diversities. We also assessed the PT modification patterns and found six new PT-linked dinucleotides (CpsG, CpsT, ApsG, TpsG, GpsC, ApsT) in human fecal DNA. To further investigate the PT in the human gut microbiome, we analyzed the abundance of PT-modifying genes and quantified the PT-linked dinucleotides in the fecal DNA. These results confirmed that human microbiome is a rich reservoir for PT-containing microbes and contains a wide variety of PT modification patterns.}, }
@article {pmid32801832, year = {2020}, author = {Lichota, A and Gwozdzinski, K and Szewczyk, EM}, title = {Microbial Modulation of Coagulation Disorders in Venous Thromboembolism.}, journal = {Journal of inflammation research}, volume = {13}, number = {}, pages = {387-400}, pmid = {32801832}, issn = {1178-7031}, abstract = {Venous thromboembolism (VTE), including deep vein thrombosis (DVT) and pulmonary embolism (PE), is the third leading cause of cardiovascular death in the world. Important risk factors of thrombosis include bed restraint, surgery, major trauma, long journeys, inflammation, pregnancy, and oral contraceptives, previous venous thromboembolism, cancer, and bacterial infections. Sepsis increases the risk of blood clot formation 2-20 times. In this review, we discussed various mechanisms related to the role of bacteria in venous thrombosis also taking into consideration the role of the human microbiome. Many known bacteria, such as Helicobacter pylori, Chlamydia pneumoniae, Mycoplasma pneumoniae, Haemophilus influenzae, Streptococcus pneumoniae, Staphylococcus aureus, and Escherichia coli, causing infections may increase the risk of thrombotic complications through platelet activation or may lead to an inflammatory reaction involving the fibrinolytic system. Additionally, the bacteria participate in the production of factors causing or increasing the risk of cardiovascular diseases. An example can be trimethylamine N-oxide (TMAO) but also uremic toxins (indoxyl sulfate), short-chain fatty acids (SCFA) phytoestrogens, and bile acids. Finally, we presented the involvement of many bacteria in the development of venous thromboembolism and other cardiovascular diseases.}, }
@article {pmid32797272, year = {2020}, author = {Bayar, E and Bennett, PR and Chan, D and Sykes, L and MacIntyre, DA}, title = {The pregnancy microbiome and preterm birth.}, journal = {Seminars in immunopathology}, volume = {42}, number = {4}, pages = {487-499}, pmid = {32797272}, issn = {1863-2300}, support = {MR/L009226/1/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Female ; Humans ; Infant, Newborn ; Lactobacillus ; *Microbiota ; Pregnancy ; *Premature Birth ; Vagina ; }, abstract = {Preterm birth is a global health concern and continues to contribute to substantial neonatal morbidity and mortality despite advances in obstetric and neonatal care. The underlying aetiology is multi-factorial and remains incompletely understood. In this review, the complex interplay between the vaginal microbiome in pregnancy and its association with preterm birth is discussed in depth. Advances in the study of bacteriology and an improved understanding of the human microbiome have seen an improved awareness of the vaginal microbiota in both health and in disease.}, }
@article {pmid32794312, year = {2021}, author = {Farahani, L and Tharakan, T and Yap, T and Ramsay, JW and Jayasena, CN and Minhas, S}, title = {The semen microbiome and its impact on sperm function and male fertility: A systematic review and meta-analysis.}, journal = {Andrology}, volume = {9}, number = {1}, pages = {115-144}, doi = {10.1111/andr.12886}, pmid = {32794312}, issn = {2047-2927}, support = {PDF-2017-10-098/DH_/Department of Health/United Kingdom ; }, mesh = {Fertility ; Humans ; Infertility, Male/*microbiology ; Male ; *Microbiota ; Semen/*microbiology ; Spermatozoa/physiology ; }, abstract = {BACKGROUND: Male factor is attributable in up to 50% of cases of infertility. In vitro studies demonstrate that bacteria can negatively impact sperm function. The use of next-generation sequencing techniques has provided a better understanding of the human microbiome, and dysbiosis has been reported to impact health. Evidence regarding the impact of the semen microbiome on sperm function and fertility remains conflicting.<br><br>MATERIALS AND METHODS: A systematic search was conducted in accordance with the Preferred Reporting Items for Reviews and Meta-analysis (PRISMA) statement. The databases MEDLINE, OVID and PubMed were searched to identify English language studies related to the identification of bacteria in the semen of infertile and fertile men, between 1992 and 2019. Fifty-five observational studies were included, with 51&#xa0;299 subjects. We included studies identifying bacteria using next-generation sequencing, culture or polymerase chain reaction.<br><br>RESULTS: The semen microbiome was rich and diverse in both fertile and infertile men. Three NGS studies reported clustering of the seminal microbiome with a predominant species. Lactobacillus and Prevotella were dominant in respective clusters. Lactobacillus was associated with improvements in semen parameters. Prevotella appeared to exert a negative effect on sperm quality. Bacteriospermia negatively impacted sperm concentration and progressive motility, and DNA fragmentation index (DFI; MD: 3.518, 95% CI: 0.907 to 6.129, P&#xa0;=&#xa0;.008). There was an increased prevalence of ureaplasma urealyticum in infertile men (OR: 2.25, 95% CI: 1.47-3.46). Ureaplasma urealyticum negatively impacted concentration and morphology. There was no difference in the prevalence of chlamydia trachomatis between fertile and infertile men and no significant impact on semen parameters. Enterococcus faecalis negatively impacted total motility, and Mycoplasma hominis negatively impacted concentration, PM and morphology.<br><br>DISCUSSION AND CONCLUSIONS: Ureaplasma urealyticum, Enterococcus faecalis, Mycoplasma hominis and Prevotella negatively impact semen parameters, whereas Lactobacillus appears to protect sperm quality. These findings may facilitate the development of novel therapies (eg probiotics), although the evidence regarding the impact of the seminal microbiome on fertility is inconclusive and further studies are needed to investigate this association.}, }
@article {pmid32793130, year = {2020}, author = {Moran, GP and Al-Hebshi, N}, title = {Editorial: The Human Microbiome and Cancer.}, journal = {Frontiers in microbiology}, volume = {11}, number = {}, pages = {1514}, pmid = {32793130}, issn = {1664-302X}, }
@article {pmid32791981, year = {2020}, author = {Yan, Y and Nguyen, LH and Franzosa, EA and Huttenhower, C}, title = {Strain-level epidemiology of microbial communities and the human microbiome.}, journal = {Genome medicine}, volume = {12}, number = {1}, pages = {71}, pmid = {32791981}, issn = {1756-994X}, support = {R24 DK110499/DK/NIDDK NIH HHS/United States ; R24DK110499//NIH NIDDK/International ; C10674/A27140//Cancer Research UK Grand Challenge Initiative/International ; }, mesh = {*Biodiversity ; Disease Susceptibility ; Gastrointestinal Microbiome ; High-Throughput Nucleotide Sequencing/methods ; Humans ; Metagenome ; *Metagenomics/methods ; *Microbiota ; Public Health Surveillance ; RNA, Ribosomal, 16S/genetics ; }, abstract = {The biological importance and varied metabolic capabilities of specific microbial strains have long been established in the scientific community. Strains have, in the past, been largely defined and characterized based on microbial isolates. However, the emergence of new technologies and techniques has enabled assessments of their ecology and phenotypes within microbial communities and the human microbiome. While it is now more obvious how pathogenic strain variants are detrimental to human health, the consequences of subtle genetic variation in the microbiome have only recently been exposed. Here, we review the operational definitions of strains (e.g., genetic and structural variants) as they can now be identified from microbial communities using different high-throughput, often culture-independent techniques. We summarize the distribution and diversity of strains across the human body and their emerging links to health maintenance, disease risk and progression, and biochemical responses to perturbations, such as diet or drugs. We list methods for identifying, quantifying, and tracking strains, utilizing high-throughput sequencing along with other molecular and "culturomics" technologies. Finally, we discuss implications of population studies in bridging experimental gaps and leading to a better understanding of the health effects of strains in the human microbiome.}, }
@article {pmid32791626, year = {2020}, author = {Wang, L and Chen, F and Yang, L and Li, J}, title = {[Role of nasal microbiome in chronic sinusitis].}, journal = {Lin chuang er bi yan hou tou jing wai ke za zhi = Journal of clinical otorhinolaryngology head and neck surgery}, volume = {34}, number = {5}, pages = {474-477}, pmid = {32791626}, issn = {2096-7993}, mesh = {Biofilms ; Chronic Disease ; Humans ; *Microbiota ; Nasal Mucosa ; *Rhinitis ; *Sinusitis ; Superantigens ; }, abstract = {Chronic sinusitis is a common disease in otolaryngology head and neck surgery, but the pathogenesis is unknown. For a long time, we have used fungi, bacterial biofilms, superantigens, and low host immunity as the cause of chronic sinusitis. With the rapid development of molecular biology technology, especially the advancement of DNA sequencing technology, people's research on human microbiome is deeper. We gradually realize the role of bacterial community in chronic sinusitis. This review will describe the role of bacteria in chronic sinusitis from three aspects: the composition of nasal bacterial community, the relationship between bacterial community and inflammatory phenotype, and the role between bacteria-host interaction.}, }
@article {pmid32791127, year = {2021}, author = {McCracken, BA and Nathalia Garcia, M}, title = {Phylum Synergistetes in the oral cavity: A possible contributor to periodontal disease.}, journal = {Anaerobe}, volume = {68}, number = {}, pages = {102250}, doi = {10.1016/j.anaerobe.2020.102250}, pmid = {32791127}, issn = {1095-8274}, mesh = {Bacteria/classification/genetics/*isolation &amp; purification ; Humans ; *Microbiota ; Mouth/*microbiology ; Periodontal Diseases/*microbiology ; Phylogeny ; }, abstract = {Microbial contributions to periodontal disease have been under renewed scrutiny with the advent of newer technologies to identify their presence and gene expression at the molecular level. Members of the phylum Synergistetes are some of the more recent bacteria to be associated with periodontal disease. Bacteria classified in this phylum can be found in a wide variety of habitats including both inside and outside of a mammalian host. Members of this phylum have been identified as part of the human microbiome. Indeed, many of the identified phylotypes have yet to be cultivated. Here we consider contributions of three named and formally described species to the oral microbial community and to pathogenesis of periodontal disease.}, }
@article {pmid32789110, year = {2020}, author = {Kim, YY and Joh, JS and Lee, JY}, title = {Importance of microbial extracellular vesicle in the pathogenesis of asthma and chronic obstructive pulmonary disease and its diagnostic potential.}, journal = {Asia Pacific allergy}, volume = {10}, number = {3}, pages = {e25}, pmid = {32789110}, issn = {2233-8276}, abstract = {There are rising evidences of the human microbiome as a potentially influential player that is actively engaged in shaping the pathogenetic processes and other unresolved issues both in asthma and other chronic respiratory diseases, particularly of the airways. The biological components such as microbiome in inhaled air can induce immune dysfunction and inflammation, leading to inflammatory pulmonary disorders such as asthma and chronic obstructive pulmonary disease (COPD). Microbe-derived extracellular vesicles (EVs) with biologically active information or functions can reprogram their respective target cells and EV may have a role for the development of asthma and COPD. To evaluate the role of microbe-derived EV in the pathogenesis of asthma and COPD and its role in diagnosis, the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement method was used for the study. An electronic search was performed using PubMed, PubMed Central, and Embase up to 2020. EVs serve as an intercellular transporter of miRNAs for cell-to-cell communication in the lungs. Bacteria-derived EVs have distinctive characteristics in the lungs of patients with asthma and COPD compared to healthy controls. Furthermore, bacterial EV IgG antibody titers in serum were significantly higher in patients with asthma and COPD than in healthy controls, suggesting that antibacterial EV antibodies titers can be used as a diagnostic tool for lung disease. Taken together, microbial EVs and miRNAs have important roles in the pathogenesis of asthma and COPD and they can provide novel diagnostic biomarkers for asthma and COPD.}, }
@article {pmid32786473, year = {2020}, author = {Jiang, X and Liu, S and Zhang, Y and Ji, Y and Sohail, A and Cao, C and Wang, P and Xiao, H}, title = {Free-Flow Isoelectric Focusing for Comprehensive Separation and Analysis of Human Salivary Microbiome for Lung Cancer.}, journal = {Analytical chemistry}, volume = {92}, number = {17}, pages = {12017-12025}, doi = {10.1021/acs.analchem.0c02627}, pmid = {32786473}, issn = {1520-6882}, mesh = {Humans ; Isoelectric Focusing/*methods ; Lung Neoplasms/*microbiology ; Microbiota/*immunology ; Saliva/cytology/*microbiology ; }, abstract = {Human microbiome contains billions of microorganisms that play important roles in the biological system and different diseases. Due to its complexity, conventional culture-independent technology may underestimate the value of low-abundance bacteria, which calls for a highly efficient method for its enrichment and comprehensive analysis. In this study, we developed a recycling free-flow isoelectric focusing (RFFIEF) method-based electrophoresis method to separate salivary microbiome. First, we used Escherichia coli (DH5α) as a model for RFFIEF method development, which was focused in a narrow pH range (0.38 pH unit). The recovery rate was 80.81% with 5.85% relative standard deviation (n = 5). The optimized method was then adopted to separate the human salivary microbiome into 32 fractions, followed by 16S rRNA gene sequencing and metaproteomics analysis. After RFFIEF fractionation, we identified 508 bacterial genera, which increased by 225% on average (n = 3) when compared to the results before fractionation. We further compared the compositional change of microbiome in the saliva of lung cancer group (n = 22) and control group (n = 21) through RFFIEF. Quantitative results demonstrated that six bacterial genera were upregulated dramatically in the lung cancer group, while two genera were downregulated. Through qPCR verification in an independent sample set (n = 48), we confirmed that genus Granulicatella was significantly upregulated in the lung cancer group, whereas Pseudomonas was remarkably downregulated (p < 0.001). RFFIEF is an efficient and reproducible technology to fractionate the microbiome for its comprehensive analysis, which can be further applied to the in-depth study of the complex microbiomes and contribute to the discovery of disease-associated bacteria.}, }
@article {pmid32782301, year = {2020}, author = {Chen, L and Collij, V and Jaeger, M and van den Munckhof, ICL and Vich Vila, A and Kurilshikov, A and Gacesa, R and Sinha, T and Oosting, M and Joosten, LAB and Rutten, JHW and Riksen, NP and Xavier, RJ and Kuipers, F and Wijmenga, C and Zhernakova, A and Netea, MG and Weersma, RK and Fu, J}, title = {Gut microbial co-abundance networks show specificity in inflammatory bowel disease and obesity.}, journal = {Nature communications}, volume = {11}, number = {1}, pages = {4018}, pmid = {32782301}, issn = {2041-1723}, support = {P30 DK043351/DK/NIDDK NIH HHS/United States ; }, mesh = {Adult ; Bacteria/growth &amp; development/isolation &amp; purification/metabolism ; Cohort Studies ; Dysbiosis/metabolism/microbiology ; Female ; *Gastrointestinal Microbiome/genetics ; Host Specificity ; Humans ; Inflammatory Bowel Diseases/metabolism/*microbiology ; Male ; Metabolic Networks and Pathways ; *Microbial Consortia ; Middle Aged ; Obesity/metabolism/*microbiology ; }, abstract = {The gut microbiome is an ecosystem that involves complex interactions. Currently, our knowledge about the role of the gut microbiome in health and disease relies mainly on differential microbial abundance, and little is known about the role of microbial interactions in the context of human disease. Here, we construct and compare microbial co-abundance networks using 2,379 metagenomes from four human cohorts: an inflammatory bowel disease (IBD) cohort, an obese cohort and two population-based cohorts. We find that the strengths of 38.6% of species co-abundances and 64.3% of pathway co-abundances vary significantly between cohorts, with 113 species and 1,050 pathway co-abundances showing IBD-specific effects and 281 pathway co-abundances showing obesity-specific effects. We can also replicate these IBD microbial co-abundances in longitudinal data from the IBD cohort of the integrative human microbiome (iHMP-IBD) project. Our study identifies several key species and pathways in IBD and obesity and provides evidence that altered microbial abundances in disease can influence their co-abundance relationship, which expands our current knowledge regarding microbial dysbiosis in disease.}, }
@article {pmid32780794, year = {2020}, author = {Crimarco, A and Springfield, S and Petlura, C and Streaty, T and Cunanan, K and Lee, J and Fielding-Singh, P and Carter, MM and Topf, MA and Wastyk, HC and Sonnenburg, ED and Sonnenburg, JL and Gardner, CD}, title = {A randomized crossover trial on the effect of plant-based compared with animal-based meat on trimethylamine-N-oxide and cardiovascular disease risk factors in generally healthy adults: Study With Appetizing Plantfood-Meat Eating Alternative Trial (SWAP-MEAT).}, journal = {The American journal of clinical nutrition}, volume = {112}, number = {5}, pages = {1188-1199}, pmid = {32780794}, issn = {1938-3207}, support = {R01 DK085025/DK/NIDDK NIH HHS/United States ; T32 HL007034/HL/NHLBI NIH HHS/United States ; UL1 TR001085/TR/NCATS NIH HHS/United States ; UL1 TR003142/TR/NCATS NIH HHS/United States ; }, mesh = {Adult ; Animals ; Cardiovascular Diseases/*prevention &amp; control ; Cattle ; Chickens ; Cross-Over Studies ; *Diet, Vegetarian ; Exercise ; Female ; Humans ; Male ; *Meat ; Methylamines/*metabolism ; Middle Aged ; Risk Factors ; }, abstract = {BACKGROUND: Despite the rising popularity of plant-based alternative meats, there is limited evidence of the health effects of these products.<br><br>OBJECTIVES: We aimed to compare the effect of consuming plant-based alternative meat (Plant) as opposed to animal meat (Animal) on health factors. The primary outcome was fasting serum trimethylamine-N-oxide (TMAO). Secondary outcomes included fasting insulin-like growth factor 1, lipids, glucose, insulin, blood pressure, and weight.<br><br>METHODS: SWAP-MEAT (The Study With Appetizing Plantfood-Meat Eating Alternatives Trial) was a single-site, randomized crossover trial with no washout period. Participants received Plant and Animal products, dietary counseling, lab assessments, microbiome assessments (16S), and anthropometric measurements. Participants were instructed to consume &#x2265;2 servings/d of Plant compared with Animal for 8 wk each, while keeping all other foods and beverages as similar as possible between the 2 phases.<br><br>RESULTS: The 36 participants who provided complete data for both crossover phases included 67% women, were 69% Caucasian, had a mean&#xa0;&#xb1;&#xa0;SD age 50&#xa0;&#xb1;&#xa0;14 y, and BMI 28&#xa0;&#xb1;&#xa0;5 kg/m2. Mean&#xa0;&#xb1;&#xa0;SD servings per day were not different by intervention sequence: 2.5&#xa0;&#xb1;&#xa0;0.6 compared with 2.6&#xa0;&#xb1;&#xa0;0.7 for Plant and Animal, respectively (P&#xa0;=&#xa0;0.76). Mean&#xa0;&#xb1;&#xa0;SEM TMAO concentrations were significantly lower overall for Plant (2.7&#xa0;&#xb1;&#xa0;0.3) than for Animal (4.7&#xa0;&#xb1;&#xa0;0.9) (P&#xa0;=&#xa0;0.012), but a significant order effect was observed (P&#xa0;=&#xa0;0.023). TMAO concentrations were significantly lower for Plant among the n&#xa0;=&#xa0;18 who received Plant second (2.9&#xa0;&#xb1;&#xa0;0.4 compared with 6.4&#xa0;&#xb1;&#xa0;1.5, Plant compared with Animal, P&#xa0;=&#xa0;0.007), but not for the n&#xa0;=&#xa0;18 who received Plant first (2.5&#xa0;&#xb1;&#xa0;0.4 compared with 3.0&#xa0;&#xb1;&#xa0;0.6, Plant compared with Animal, P&#xa0;=&#xa0;0.23). Exploratory analyses of the microbiome failed to reveal possible responder compared with nonresponder factors. Mean&#xa0;&#xb1;&#xa0;SEM LDL-cholesterol concentrations (109.9&#xa0;&#xb1;&#xa0;4.5 compared with 120.7&#xa0;&#xb1;&#xa0;4.5 mg/dL, P&#xa0;=&#xa0;0.002) and weight (78.7&#xa0;&#xb1;&#xa0;3.0 compared with 79.6&#xa0;&#xb1;&#xa0;3.0 kg, P&#xa0;<&#xa0;0.001) were lower during the Plant phase.<br><br>CONCLUSIONS: Among generally healthy adults, contrasting Plant with Animal intake, while keeping all other dietary components similar, the Plant products improved several cardiovascular disease risk factors, including TMAO; there were no adverse effects on risk factors from the Plant products.This trial was registered at clinicaltrials.gov as NCT03718988.}, }
@article {pmid32778754, year = {2020}, author = {Cairns, J and Jokela, R and Becks, L and Mustonen, V and Hiltunen, T}, title = {Repeatable ecological dynamics govern the response of experimental communities to antibiotic pulse perturbation.}, journal = {Nature ecology &amp; evolution}, volume = {4}, number = {10}, pages = {1385-1394}, pmid = {32778754}, issn = {2397-334X}, mesh = {*Anti-Bacterial Agents ; Bacteria/genetics ; Metagenome ; *Microbiota ; Residence Characteristics ; }, abstract = {In an era of pervasive anthropogenic ecological disturbances, there is a pressing need to understand the factors that constitute community response and resilience. A detailed understanding of disturbance response needs to go beyond associations and incorporate features of disturbances, species traits, rapid evolution and dispersal. Multispecies microbial communities that experience antibiotic perturbation represent a key system with important medical dimensions. However, previous microbiome studies on this theme have relied on high-throughput sequencing data from uncultured species without the ability to explicitly account for the role of species traits and immigration. Here, we serially passage a 34-species defined bacterial community through different levels of pulse antibiotic disturbance, manipulating the presence or absence of species immigration. To understand the ecological community response measured using amplicon sequencing, we combine initial trait data measured for each species separately and metagenome sequencing data revealing adaptive mutations during the experiment. We found that the ecological community response was highly repeatable within the experimental treatments, which could be attributed in part to key species traits (antibiotic susceptibility and growth rate). Increasing antibiotic levels were also coupled with an increasing probability of species extinction, making species immigration critical for community resilience. Moreover, we detected signals of antibiotic-resistance evolution occurring within species at the same time scale, leaving evolutionary changes in communities despite recovery at the species compositional level. Together, these observations reveal a disturbance response that presents as classic species sorting, but is nevertheless accompanied by rapid within-species evolution.}, }
@article {pmid32775155, year = {2020}, author = {Méhes, G and Roy, A and Strakosas, X and Berggren, M and Stavrinidou, E and Simon, DT}, title = {Organic Microbial Electrochemical Transistor Monitoring Extracellular Electron Transfer.}, journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)}, volume = {7}, number = {15}, pages = {2000641}, pmid = {32775155}, issn = {2198-3844}, abstract = {Extracellular electron transfer (EET) denotes the process of microbial respiration with electron transfer to extracellular acceptors and has been exploited in a range of microbial electrochemical systems (MESs). To further understand EET and to optimize the performance of MESs, a better understanding of the dynamics at the microscale is needed. However, the real-time monitoring of EET at high spatiotemporal resolution would require sophisticated signal amplification. To amplify local EET signals, a miniaturized bioelectronic device, the so-called organic microbial electrochemical transistor (OMECT), is developed, which includes Shewanella oneidensis MR-1 integrated onto organic electrochemical transistors comprising poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) combined with poly(vinyl alcohol) (PVA). Bacteria are attached to the gate of the transistor by a chronoamperometric method and the successful attachment is confirmed by fluorescence microscopy. Monitoring EET with the OMECT configuration is achieved due to the inherent amplification of the transistor, revealing fast time-responses to lactate. The limits of detection when using microfabricated gates as charge collectors are also investigated. The work is a first step toward understanding and monitoring EET in highly confined spaces via microfabricated organic electronic devices, and it can be of importance to study exoelectrogens in microenvironments, such as those of the human microbiome.}, }
@article {pmid32772665, year = {2020}, author = {Chomicki, G and Werner, GDA and West, SA and Kiers, ET}, title = {Compartmentalization drives the evolution of symbiotic cooperation.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {375}, number = {1808}, pages = {20190602}, pmid = {32772665}, issn = {1471-2970}, mesh = {Animals ; *Bacterial Physiological Phenomena ; Decapodiformes/microbiology ; Fabaceae/*microbiology ; Fungi/*physiology ; Humans ; Insecta/*microbiology ; *Microbiota ; Plants/*microbiology ; *Symbiosis ; Vibrio/physiology ; }, abstract = {Across the tree of life, hosts have evolved mechanisms to control and mediate interactions with symbiotic partners. We suggest that the evolution of physical structures that allow hosts to spatially separate symbionts, termed compartmentalization, is a common mechanism used by hosts. Such compartmentalization allows hosts to: (i) isolate symbionts and control their reproduction; (ii) reward cooperative symbionts and punish or stop interactions with non-cooperative symbionts; and (iii) reduce direct conflict among different symbionts strains in a single host. Compartmentalization has allowed hosts to increase the benefits that they obtain from symbiotic partners across a diversity of interactions, including legumes and rhizobia, plants and fungi, squid and Vibrio, insects and nutrient provisioning bacteria, plants and insects, and the human microbiome. In cases where compartmentalization has not evolved, we ask why not. We argue that when partners interact in a competitive hierarchy, or when hosts engage in partnerships which are less costly, compartmentalization is less likely to evolve. We conclude that compartmentalization is key to understanding the evolution of symbiotic cooperation. This article is part of the theme issue 'The role of the microbiome in host evolution'.}, }
@article {pmid32771801, year = {2020}, author = {Eggers, S and Gennings, C and Malecki, KMC and Safdar, N and Arora, M}, title = {Exposure to environmental chemical mixtures is associated with nasal colonization by Staphylococcus aureus: NHANES 2001-2004.}, journal = {Environmental research}, volume = {190}, number = {}, pages = {109994}, pmid = {32771801}, issn = {1096-0953}, support = {R01 ES026033/ES/NIEHS NIH HHS/United States ; DP2 ES025453/ES/NIEHS NIH HHS/United States ; P30 ES023515/ES/NIEHS NIH HHS/United States ; T32 HD049311/HD/NICHD NIH HHS/United States ; U2C ES030859/ES/NIEHS NIH HHS/United States ; }, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Carrier State ; Child ; Female ; Humans ; *Methicillin-Resistant Staphylococcus aureus ; Middle Aged ; Nutrition Surveys ; Prevalence ; Risk Factors ; *Staphylococcal Infections/epidemiology ; Staphylococcus aureus ; Young Adult ; }, abstract = {BACKGROUND: Understanding the health effects of exposure to chemical mixtures is critically important given the broad range of concurrent exposures throughout the life-course. While investigations of environmental chemicals and components of the human microbiome are becoming more common, few have examined associations with chemical mixtures. This study assesses the association between exposure to mixtures of 66 different environmental chemicals and nasal colonization of Staphylococcus aureus (SA) and methicillin resistant SA (MRSA).<br><br>METHODS: Data came from the National Health and Nutrition Examination Survey (NHANES) 2001-2004. The analytical sample consists of 10,312 participants, age 6 years and older, subdivided into 8 groups with different chemical exposure mixtures. Within each of 6 chemical classes (metals, phthalates, polycyclic aromatic hydrocarbons (PAHs), polybrominated diphenyl ethers (PBDEs), polyfluorochemicals (PFCs), and phenols), weighted quantile sum (WQS) regression was used to analyze the joint association of the component compounds and nasal SA colonization. WQS was also used to assess the joint association of 3 chemical mixtures (metals, metal and PAHs, and metal and triclosan) and nasal MRSA colonization. All regression models were adjusted for confounders.<br><br>RESULTS: The analytical sample was between ages 6-85, slightly more female, and predominantly non-smokers. Prevalence of SA carriage was 29.2%, and MRSA colonization prevalence was 1.2%. Within each chemical class, odds of SA colonization increased statistically significantly with exposure to mixtures of metals (OR&#xa0;=&#xa0;1.11, 95% CI&#xa0;=&#xa0;1.02-1.20), phthalates (OR&#xa0;=&#xa0;1.09, 95% CI&#xa0;=&#xa0;1.04-1.14), and phenols (OR&#xa0;=&#xa0;1.08, 95% CI&#xa0;=&#xa0;1.01-1.15). Exposure to a mixture of metals combined with PAHs was also associated with increased odds of MRSA carriage (OR&#xa0;=&#xa0;1.38, 95% CI&#xa0;=&#xa0;1.02-1.86).<br><br>CONCLUSION: Results indicate an association between multiple environmental chemical mixtures and SA colonization, including MRSA. These findings support the need for further analysis of associations between chemical mixtures and SA colonization, as well as other components of the human microbiome.}, }
@article {pmid32770635, year = {2020}, author = {Tan, Y and Shen, J and Si, T and Ho, CL and Li, Y and Dai, L}, title = {Engineered Live Biotherapeutics: Progress and Challenges.}, journal = {Biotechnology journal}, volume = {15}, number = {10}, pages = {e2000155}, doi = {10.1002/biot.202000155}, pmid = {32770635}, issn = {1860-7314}, support = {2019YFA09006700//National Key R&amp;D Program of China/ ; DWKF20190001//Shenzhen Institute of Synthetic Biology/ ; Y8G023//SIAT Innovation Program for Excellent Young Researchers/ ; 2019M663166//China Postdoctoral Science Foundation/ ; //IDG-McGovern Institute for Brain Research and the School of Pharmaceutical Sciences at Tsinghua University/ ; 31971513//National Natural Science Foundation of China/ ; }, mesh = {Bacteria ; Humans ; Microbial Consortia ; *Microbiota ; *Synthetic Biology ; }, abstract = {The human microbiome plays an important role in human health, from metabolism to immunity. In the last few decades, advances in synthetic biology have enabled scientists to design and engineer live microorganisms for therapeutic purposes. In this review, major strategies for manipulating the microbiome are outlined, which include three emerging areas with promising therapeutic applications: engineered commensal bacteria, synthetic microbial consortia, and targeted modulation by phages. Furthermore, the applications of engineered live biotherapeutics in treating a variety of human diseases, including pathogenic infections, metabolic disorders, inflammatory bowel disease, and colorectal cancer, are highlighted. Finally, an overview of the challenges and opportunities in the future development of engineered live biotherapeutics is provided.}, }
@article {pmid32767183, year = {2020}, author = {Tan, GSE and Tay, HL and Tan, SH and Lee, TH and Ng, TM and Lye, DC}, title = {Gut Microbiota Modulation: Implications for Infection Control and Antimicrobial Stewardship.}, journal = {Advances in therapy}, volume = {37}, number = {10}, pages = {4054-4067}, pmid = {32767183}, issn = {1865-8652}, mesh = {*Antimicrobial Stewardship ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; Infection Control ; *Microbiota ; }, abstract = {The human microbiome comprises a complex ecosystem of microbial communities that exist within the human body, the largest and most diverse of which are found within the human intestine. It has been increasingly implicated in human health and diseases, demonstrably playing a critical role in influencing host immune response, protection against pathogen overgrowth, biosynthesis, and metabolism. As our understanding of the links between the gut microbiota with host immunity and infectious diseases deepens, there is a greater need to incorporate methods of modulating it as a means of therapy or infection prevention in daily clinical practice. Traditional antimicrobial stewardship principles have been evaluated to assess their impact on the gut microbiota diversity and the consequent repercussions, taking into consideration antibiotic pharmacokinetic and pharmacodynamic properties. Novel strategies of selective digestive decontamination and fecal microbiota transplantation to regulate the gut microbiota have also been tested in different conditions with variable results. This review seeks to provide an overview of the available literature on the modulation of the gut microbiota and its implications for infection control and antimicrobial stewardship. With increased understanding, gut microbiota profiling through metataxonomic analysis may provide further insight into modulating microbial communities in the context of infection prevention and control.}, }
@article {pmid32762083, year = {2020}, author = {Kantonen, J and Mahzabin, S and Mäyränpää, MI and Tynninen, O and Paetau, A and Andersson, N and Sajantila, A and Vapalahti, O and Carpén, O and Kekäläinen, E and Kantele, A and Myllykangas, L}, title = {Neuropathologic features of four autopsied COVID-19 patients.}, journal = {Brain pathology (Zurich, Switzerland)}, volume = {30}, number = {6}, pages = {1012-1016}, pmid = {32762083}, issn = {1750-3639}, support = {//Juho Vainion S&#xe4;&#xe4;ti&#xf6;/International ; //Suomen L&#xe4;&#xe4;ketieteen S&#xe4;&#xe4;ti&#xf6;/International ; //Medicinska Underst&#xf6;dsf&#xf6;reningen Liv och H&#xe4;lsa/International ; //Helsingin ja Uudenmaan Sairaanhoitopiiri/International ; 294817//Academy of Finland/International ; 334812//Academy of Finland/International ; 308913//Academy of Finland/International ; }, mesh = {Adult ; Aged, 80 and over ; Autopsy ; Brain/*pathology ; COVID-19/*pathology ; Female ; Humans ; Male ; Middle Aged ; SARS-CoV-2 ; }, }
@article {pmid32760391, year = {2020}, author = {Jouhten, H and Ronkainen, A and Aakko, J and Salminen, S and Mattila, E and Arkkila, P and Satokari, R}, title = {Cultivation and Genomics Prove Long-Term Colonization of Donor's Bifidobacteria in Recurrent Clostridioides difficile Patients Treated With Fecal Microbiota Transplantation.}, journal = {Frontiers in microbiology}, volume = {11}, number = {}, pages = {1663}, pmid = {32760391}, issn = {1664-302X}, abstract = {Fecal microbiota transplantation (FMT) is an effective treatment for recurrent Clostridioides difficile infection (rCDI) and it's also considered for treating other indications. Metagenomic studies have indicated that commensal donor bacteria may colonize FMT recipients, but cultivation has not been employed to verify strain-level colonization. We combined molecular profiling of Bifidobacterium populations with cultivation, molecular typing, and whole genome sequencing (WGS) to isolate and identify strains that were transferred from donors to recipients. Several Bifidobacterium strains from two donors were recovered from 13 recipients during the 1-year follow-up period after FMT. The strain identities were confirmed by WGS and comparative genomics. Our results show that specific donor-derived bifidobacteria can colonize rCDI patients for at least 1 year, and thus FMT may have long-term consequences for the recipient's microbiota and health. Conceptually, we demonstrate that FMT trials combined with microbial profiling can be used as a platform for discovering and isolating commensal strains with proven colonization capacity for potential therapeutic use.}, }
@article {pmid32756341, year = {2020}, author = {Sierra, MA and Li, Q and Pushalkar, S and Paul, B and Sandoval, TA and Kamer, AR and Corby, P and Guo, Y and Ruff, RR and Alekseyenko, AV and Li, X and Saxena, D}, title = {The Influences of Bioinformatics Tools and Reference Databases in Analyzing the Human Oral Microbial Community.}, journal = {Genes}, volume = {11}, number = {8}, pages = {}, pmid = {32756341}, issn = {2073-4425}, support = {R01 LM012517/LM/NLM NIH HHS/United States ; CA206105/NH/NIH HHS/United States ; DE025992/NH/NIH HHS/United States ; DE027074/NH/NIH HHS/United States ; }, mesh = {Computational Biology/methods/*standards ; DNA Barcoding, Taxonomic/methods/standards ; Databases, Genetic/*standards ; Humans ; *Microbiota ; Mouth/*microbiology ; RNA, Ribosomal, 16S/genetics ; }, abstract = {There is currently no criterion to select appropriate bioinformatics tools and reference databases for analysis of 16S rRNA amplicon data in the human oral microbiome. Our study aims to determine the influence of multiple tools and reference databases on α-diversity measurements and β-diversity comparisons analyzing the human oral microbiome. We compared the results of taxonomical classification by Greengenes, the Human Oral Microbiome Database (HOMD), National Center for Biotechnology Information (NCBI) 16S, SILVA, and the Ribosomal Database Project (RDP) using Quantitative Insights Into Microbial Ecology (QIIME) and the Divisive Amplicon Denoising Algorithm (DADA2). There were 15 phyla present in all of the analyses, four phyla exclusive to certain databases, and different numbers of genera were identified in each database. Common genera found in the oral microbiome, such as Veillonella, Rothia, and Prevotella, are annotated by all databases; however, less common genera, such as Bulleidia and Paludibacter, are only annotated by large databases, such as Greengenes. Our results indicate that using different reference databases in 16S rRNA amplicon data analysis could lead to different taxonomic compositions, especially at genus level. There are a variety of databases available, but there are no defined criteria for data curation and validation of annotations, which can affect the accuracy and reproducibility of results, making it difficult to compare data across studies.}, }
@article {pmid32755361, year = {2020}, author = {Afzal, M and Mazhar, SF and Sana, S and Naeem, M and Rasool, MH and Saqalein, M and Nisar, MA and Rasool, M and Bilal, M and Khan, AA and Khurshid, M}, title = {Neurological and cognitive significance of probiotics: a holy grail deciding individual personality.}, journal = {Future microbiology}, volume = {15}, number = {}, pages = {1059-1074}, doi = {10.2217/fmb-2019-0143}, pmid = {32755361}, issn = {1746-0921}, mesh = {Animals ; Brain/drug effects/*physiology ; Cognition/*drug effects ; Gastrointestinal Microbiome/*drug effects ; Humans ; Personality/*drug effects ; Probiotics/*pharmacology ; }, abstract = {The role of the human microbiome in the brain and behavioral development is an area of increasing attention. Recent investigations have found that diverse mechanisms and signals including the immune, endocrine and neural associations are responsible for the communication between gut microbiota and the brain. The studies have suggested that alteration of intestinal microbiota using probiotic formulations may offer a significant role in the maturation and organization of the brain and can shape the brain and behavior as well as mood and cognition in human subjects. The understanding of the possible impact of gut microflora on neurological function is a promising phenomenon that can surely transform the neurosciences and may decipher the novel etiologies for neurodegenerative and psychiatric disorders.}, }
@article {pmid32754400, year = {2020}, author = {Achufusi, TGO and Sharma, A and Zamora, EA and Manocha, D}, title = {Small Intestinal Bacterial Overgrowth: Comprehensive Review of Diagnosis, Prevention, and Treatment Methods.}, journal = {Cureus}, volume = {12}, number = {6}, pages = {e8860}, pmid = {32754400}, issn = {2168-8184}, abstract = {Small intestinal bacterial overgrowth (SIBO) is a commonly diagnosed gastrointestinal disorder affecting millions of individuals throughout the United States. It refers to a condition in which there is an excess and imbalance of small intestinal bacteria. Despite its prevalence, it remains underdiagnosed due to the invasive nature of diagnostic testing. Symptoms observed in SIBO, including abdominal distension, bloating, diarrhea, and gas formation, are nonspecific and can overlap with other gastrointestinal disorders. Frequently cited predisposing factors include gastric acid suppression, dysmotility, gastric bypass, and opioids. The diagnostic gold standard remains small bowel aspirate and culture. However, due to its invasive nature, it remains an unpopular method among patients and clinicians alike. Glucose and lactulose breath testing have become the go-to diagnostic method in clinical practice due to its noninvasive nature and low cost. Treatment is guided towards the eradication of bacteria in the small bowel and usually consists of a prolonged course of oral antibiotics. Due to recent advances in our understanding of the human microbiome, we are surely poised for a transformation in our approach to diagnosing and treating this condition.}, }
@article {pmid32753361, year = {2020}, author = {García-Velasco, JA and Budding, D and Campe, H and Malfertheiner, SF and Hamamah, S and Santjohanser, C and Schuppe-Koistinen, I and Nielsen, HS and Vieira-Silva, S and Laven, J}, title = {The reproductive microbiome - clinical practice recommendations for fertility specialists.}, journal = {Reproductive biomedicine online}, volume = {41}, number = {3}, pages = {443-453}, doi = {10.1016/j.rbmo.2020.06.014}, pmid = {32753361}, issn = {1472-6491}, mesh = {Female ; Fertility/physiology ; Humans ; Microbiota/*physiology ; Practice Guidelines as Topic ; Pregnancy ; Pregnancy Outcome ; Reproduction/*physiology ; *Reproductive Techniques, Assisted ; }, abstract = {The interest in and understanding of the human microbiome has grown remarkably over recent years. Advances in molecular techniques have allowed researchers to identify and study the microbiota and also use this information to develop therapeutic solutions for a spectrum of conditions. Alongside the growing interest in the microbiome, societal changes have resulted in many couples looking to start families later in life, therefore increasing the demand for assisted reproductive technologies. Combining these trends, it makes sense that clinicians are eager to understand and exploit the microbiome of their patients, i.e. the reproductive microbiome, in order to help them achieve their goal of becoming parents. This paper aims to provide an overview of the current and future research into the reproductive microbiome in relation to fertility and also share clinical practice recommendations for physicians who are new to this field or unsure about how they can utilise what is known to help their patients.}, }
@article {pmid32733788, year = {2020}, author = {Guan, X and Ma, F and Sun, X and Li, C and Li, L and Liang, F and Li, S and Yi, Z and Liu, B and Xu, B}, title = {Gut Microbiota Profiling in Patients With HER2-Negative Metastatic Breast Cancer Receiving Metronomic Chemotherapy of Capecitabine Compared to Those Under Conventional Dosage.}, journal = {Frontiers in oncology}, volume = {10}, number = {}, pages = {902}, pmid = {32733788}, issn = {2234-943X}, abstract = {Purpose: Low-dose metronomic chemotherapy can achieve disease control with reduced toxicity compared to conventional chemotherapy in maximum tolerated dose. Characterizing the gut microbiota of cancer patients under different dosage regimens may describe a new role of gut microbiota associated with drug efficacy. Therefore, we evaluated the composition and the function of gut microbiome associated with metronomic capecitabine compared to conventional dosage. Methods: The fecal samples of HER2-negative metastatic breast cancer patients treated with capecitabine as maintenance chemotherapy were collected and analyzed by 16S ribosome RNA gene sequencing. Results: A total of 15 patients treated with metronomic capecitabine were compared to 16 patients under a conventional dose. The unweighted-unifrac index of the metronomic group was statistically significantly lower than that of the routine group (P = 0.025). Besides that, the Bray-Curtis distance-based redundancy analysis illustrated that the microbial genera between the two groups can be separated partly. Nine Kyoto Encyclopedia of Genes and Genomes (KEGG) modules were enriched in the metronomic group, while no KEGG modules were significantly enriched in the routine group. Moreover, univariate and multivariate analyses suggested that the median progression-free survival (PFS) was significantly shorter in patients with the gut microbial composition of Slackia (9.2 vs. 32.7 months, P = 0.004), while the patients with Blautia obeum had a significantly prolonged PFS than those without (32.7 vs. 12.9 months, P = 0.013). Conclusions: The proof-of-principle study suggested that the gut microbiota of patients receiving metronomic chemotherapy was different in terms of diversity, composition, and function from those under conventional chemotherapy, and the presence of specific bacterial species may act as microbial markers associated with drug resistance monitoring and prognostic evaluation.}, }
@article {pmid32729247, year = {2020}, author = {Fontana, F and Lindstedt, H and Correia, A and Chiaro, J and Kari, OK and Ndika, J and Alenius, H and Buck, J and Sieber, S and Mäkilä, E and Salonen, J and Urtti, A and Cerullo, V and Hirvonen, JT and Santos, HA}, title = {Influence of Cell Membrane Wrapping on the Cell-Porous Silicon Nanoparticle Interactions.}, journal = {Advanced healthcare materials}, volume = {9}, number = {17}, pages = {e2000529}, doi = {10.1002/adhm.202000529}, pmid = {32729247}, issn = {2192-2659}, mesh = {Cell Membrane ; Endocytosis ; Humans ; *Nanoparticles ; Porosity ; *Protein Corona ; Silicon ; }, abstract = {Biohybrid nanosystems represent the cutting-edge research in biofunctionalization of micro- and nano-systems. Their physicochemical properties bring along advantages in the circulation time, camouflaging from the phagocytes, and novel antigens. This is partially a result of the qualitative differences in the protein corona, and the preferential targeting and uptake in homologous cells. However, the effect of the cell membrane on the cellular endocytosis mechanisms and time has not been fully evaluated yet. Here, the effect is assessed by quantitative flow cytometry analysis on the endocytosis of hydrophilic, negatively charged porous silicon nanoparticles and on their membrane-coated counterparts, in the presence of chemical inhibitors of different uptake pathways. Principal component analysis is used to analyze all the data and extrapolate patterns to highlight the cell-specific differences in the endocytosis mechanisms. Furthermore, the differences in the composition of static protein corona between naked and coated particles are investigated together with how these differences affect the interaction with human macrophages. Overall, the presence of the cell membrane only influences the speed and the entity of nanoparticles association with the cells, while there is no direct effect on the endocytosis pathways, composition of protein corona, or any reduction in macrophage-mediated uptake.}, }
@article {pmid32727720, year = {2020}, author = {Huybrechts, I and Zouiouich, S and Loobuyck, A and Vandenbulcke, Z and Vogtmann, E and Pisanu, S and Iguacel, I and Scalbert, A and Indave, I and Smelov, V and Gunter, MJ and Michels, N}, title = {The Human Microbiome in Relation to Cancer Risk: A Systematic Review of Epidemiologic Studies.}, journal = {Cancer epidemiology, biomarkers &amp; prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology}, volume = {29}, number = {10}, pages = {1856-1868}, pmid = {32727720}, issn = {1538-7755}, support = {001/WHO_/World Health Organization/International ; ZIA CP010127//Intramural NIH HHS/United States ; }, mesh = {Gastrointestinal Microbiome/*immunology ; Humans ; Neoplasms/*epidemiology/*etiology/pathology ; Risk ; }, abstract = {The microbiome has been hypothesized to play a role in cancer development. Because of the diversity of published data, an overview of available epidemiologic evidence linking the microbiome with cancer is now needed. We conducted a systematic review using a tailored search strategy in Medline and EMBASE databases to identify and summarize the current epidemiologic literature on the relationship between the microbiome and different cancer outcomes published until December 2019. We identified 124 eligible articles. The large diversity of parameters used to describe microbial composition made it impossible to harmonize the different studies in a way that would allow meta-analysis, therefore only a qualitative description of results could be performed. Fifty studies reported differences in the gut microbiome between patients with colorectal cancer and various control groups. The most consistent findings were for Fusobacterium, Porphyromonas, and Peptostreptococcus being significantly enriched in fecal and mucosal samples from patients with colorectal cancer. For the oral microbiome, significantly increased and decreased abundance was reported for Fusobacterium and Streptococcus, respectively, in patients with oral cancer compared with controls. Overall, although there was a large amount of evidence for some of these alterations, most require validation in high-quality, preferably prospective, epidemiologic studies.}, }
@article {pmid32725676, year = {2021}, author = {Druart, C and Plovier, H and Van Hul, M and Brient, A and Phipps, KR and de Vos, WM and Cani, PD}, title = {Toxicological safety evaluation of pasteurized Akkermansia muciniphila.}, journal = {Journal of applied toxicology : JAT}, volume = {41}, number = {2}, pages = {276-290}, pmid = {32725676}, issn = {1099-1263}, mesh = {Akkermansia/*growth &amp; development/*radiation effects ; Animals ; Dietary Supplements/*toxicity ; *Food Safety ; Gastrointestinal Microbiome/*radiation effects ; Humans ; Male ; Models, Animal ; *Pasteurization ; Rats ; Rats, Wistar ; }, abstract = {Gut microorganisms are vital for many aspects of human health, and the commensal bacterium Akkermansia muciniphila has repeatedly been identified as a key component of intestinal microbiota. Reductions in A. muciniphila abundance are associated with increased prevalence of metabolic disorders such as obesity and type 2 diabetes. It was recently discovered that administration of A. muciniphila has beneficial effects and that these are not diminished, but rather enhanced after pasteurization. Pasteurized A. muciniphila is proposed for use as a food ingredient, and was therefore subjected to a nonclinical safety assessment, comprising genotoxicity assays (bacterial reverse mutation and in vitro mammalian cell micronucleus tests) and a 90-day toxicity study. For the latter, Han Wistar rats were administered with the vehicle or pasteurized A. muciniphila at doses of 75, 375 or 1500 mg/kg body weight/day (equivalent to 4.8 × 10[9] , 2.4 × 10[10] , or 9.6 × 10[10] A. muciniphila cells/kg body weight/day) by oral gavage for 90 consecutive days. The study assessed potential effects on clinical observations (including detailed arena observations and a modified Irwin test), body weight, food and water consumption, clinical pathology, organ weights, and macroscopic and microscopic pathology. The results of both in vitro genotoxicity studies were negative. No test item-related adverse effects were observed in the 90-day study; therefore, 1500 mg/kg body weight/day (the highest dose tested, equivalent to 9.6 × 10[10] A. muciniphila cells/kg body weight/day) was established as the no-observed-adverse-effect-level. These results support that pasteurized A. muciniphila is safe for use as a food ingredient.}, }
@article {pmid32723799, year = {2020}, author = {Rojas, MI and Cavalcanti, GS and McNair, K and Benler, S and Alker, AT and Cobián-Güemes, AG and Giluso, M and Levi, K and Rohwer, F and Bailey, BA and Beyhan, S and Edwards, RA and Shikuma, NJ}, title = {A Distinct Contractile Injection System Gene Cluster Found in a Majority of Healthy Adult Human Microbiomes.}, journal = {mSystems}, volume = {5}, number = {4}, pages = {}, pmid = {32723799}, issn = {2379-5077}, abstract = {Many commensal bacteria antagonize each other or their host by producing syringe-like secretion systems called contractile injection systems (CIS). Members of the Bacteroidales family have been shown to produce only one type of CIS-a contact-dependent type 6 secretion system that mediates bacterium-bacterium interactions. Here, we show that a second distinct cluster of genes from Bacteroidales bacteria from the human microbiome may encode yet-uncharacterized injection systems that we term Bacteroidales injection systems (BIS). We found that BIS genes are present in the gut microbiomes of 99% of individuals from the United States and Europe and that BIS genes are more prevalent in the gut microbiomes of healthy individuals than in those individuals suffering from inflammatory bowel disease. Gene clusters similar to that of the BIS mediate interactions between bacteria and diverse eukaryotes, like amoeba, insects, and tubeworms. Our findings highlight the ubiquity of the BIS gene cluster in the human gut and emphasize the relevance of the gut microbiome to the human host. These results warrant investigations into the structure and function of the BIS and how they might mediate interactions between Bacteroidales bacteria and the human host or microbiome.IMPORTANCE To engage with host cells, diverse pathogenic bacteria produce syringe-like structures called contractile injection systems (CIS). CIS are evolutionarily related to the contractile tails of bacteriophages and are specialized to puncture membranes, often delivering effectors to target cells. Although CIS are key for pathogens to cause disease, paradoxically, similar injection systems have been identified within healthy human microbiome bacteria. Here, we show that gene clusters encoding a predicted CIS, which we term Bacteroidales injection systems (BIS), are present in the microbiomes of nearly all adult humans tested from Western countries. BIS genes are enriched within human gut microbiomes and are expressed both in vitro and in vivo Further, a greater abundance of BIS genes is present within healthy gut microbiomes than in those humans with with inflammatory bowel disease (IBD). Our discovery provides a potentially distinct means by which our microbiome interacts with the human host or its microbiome.}, }
@article {pmid32722412, year = {2020}, author = {Nazik, H and Sass, G and Déziel, E and Stevens, DA}, title = {Aspergillus Is Inhibited by Pseudomonas aeruginosa Volatiles.}, journal = {Journal of fungi (Basel, Switzerland)}, volume = {6}, number = {3}, pages = {}, pmid = {32722412}, issn = {2309-608X}, support = {CIMR no. 3770//The Flatley Foundation/ ; }, abstract = {BACKGROUND: Pseudomonas aeruginosa (Pa) and Aspergillus fumigatus (Af) compete with each other for nutrients and survival in natural environments, and have been extensively studied because of their intermicrobial interactions in the human microbiome. These are the principal microbes infecting immunocompromised patients and persons with cystic fibrosis, particularly the airways. These intermicrobial studies have largely been conducted in liquid medium or on agar, and thus focus on soluble or diffusible microbial products. Several key inhibitory molecules were defined in such studies.<br><br>METHODS: in the present report, we examine several methodologies which can be conveniently used to study the interaction of microbial volatiles, including capture methods and kinetics.<br><br>RESULTS: Pa volatiles inhibit Af, and the inhibitory mechanism appears to be the incorporation of the inhibitory molecules into the substrate nourishing the Af, rather than directly onto Af structures. We define by mass spectroscopy some specific volatile Pa products that can inhibit Af. Some of these molecules are selected for interest by the study of gene deletion mutants, producing a few Pa strains that were impaired in inhibition. We presumed the volatiles of these latter strains could be excluded from the search for inhibitors.<br><br>CONCLUSION: the Pa inhibition of Af via a gaseous phase could be critical components in their competition, particularly in airways, where more direct contact may not be extensive.}, }
@article {pmid32721621, year = {2020}, author = {Pearson, AL and Pechal, J and Lin, Z and Benbow, ME and Schmidt, C and Mavoa, S}, title = {Associations detected between measures of neighborhood environmental conditions and human microbiome diversity.}, journal = {The Science of the total environment}, volume = {745}, number = {}, pages = {141029}, doi = {10.1016/j.scitotenv.2020.141029}, pmid = {32721621}, issn = {1879-1026}, mesh = {Humans ; *Microbiota ; Plants ; Soil ; *Soil Microbiology ; Trees ; }, abstract = {While emerging research suggests urban green space revegetation increases soil microbiota diversity and native plant species affect skin microbiome diversity, there is still a paucity of knowledge on relationships between neighborhood environmental conditions and the human microbiome. This study leveraged data on human microbiome samples (nose, mouth, rectum) taken at autopsy at the Wayne County Medical Examiner's Office (2014-2015). We evaluated relationships between the microbiome and five measures of environmental conditions (NDVI standard deviation, NDVI mean, percent trees, percent grassland and soil type) near the home of 126 decedents. For the rectum microbiome, NDVI sd had negative, significant associations with diversity (ASVs β = -0.20, p = 0.045; Faith PD β = -0.22, p = 0.026). In contrast, while insignificant, there were consistent, positive associations between diversity and NDVI sd for the mouth microbiome (ASVs β = 0.09, p = 0.337, Faith PD β = 0.14, p = 0.149, Shannon diversity β = 0.14, p = 0.159, Heip's evenness β = 0.11, p = 0.259) and a significant association for the nose microbiome (eigenvalues 3 β = 0.18, p = 0.057). We found consistent, significant, negative associations between percent grassland and diversity of the nose microbiome (ASVs β = -0.25, p = 0.008, Faith PD β = -0.25, p = 0.009, Shannon diversity β = -0.17, p = 0.062). For the mouth microbiome, we found a small effect of percent trees on diversity (eigenvalues 1 β = -0.08, p = 0.053). Clay loam soil was negatively (eigenvalues 2 β = -0.47, p = 0.053) and positively associated (eigenvalues 3 β = 0.65, p = 0.008) with rectum microbiome diversity, compared to loam soil. There was no potential indicator taxon among NDVI quartiles. These findings may be relevant for urban planning and management of urban outdoor spaces in ways that may support healthy human microbiomes. Still, future research is needed to link variation in NDVI, vegetation, plant and/or soil microbe diversity and to confirm or negate our findings that environmental conditions may have contrasting influence on the microbiome of the rectum versus the nose and mouth and that grasslands affect the nose microbiome.}, }
@article {pmid32717337, year = {2021}, author = {Chadha, J and Nandi, D and Atri, Y and Nag, A}, title = {Significance of human microbiome in breast cancer: Tale of an invisible and an invincible.}, journal = {Seminars in cancer biology}, volume = {70}, number = {}, pages = {112-127}, doi = {10.1016/j.semcancer.2020.07.010}, pmid = {32717337}, issn = {1096-3650}, mesh = {Animals ; Antineoplastic Agents/*administration &amp; dosage ; Breast Neoplasms/*drug therapy/microbiology ; Female ; *Gastrointestinal Microbiome ; Humans ; Prebiotics/*administration &amp; dosage ; *Precision Medicine ; }, abstract = {The human microbiome is a mysterious treasure of the body playing endless important roles in the well-being of the host metabolism, digestion, and immunity. On the other hand, it actively participates in the development of a variety of pathological conditions including cancer. With the Human Microbiome Project initiative, metagenomics, and next-generation sequencing technologies in place, the last decade has witnessed immense explorations and investigations on the enigmatic association of breast cancer with the human microbiome. However, the connection between the human microbiome and breast cancer remains to be explored in greater detail. In fact, there are several emerging questions such as whether the host microbiota contributes to disease initiation, or is it a consequence of the disease is an irrevocably important question that demands a valid answer. Since the microbiome is an extremely complex community, gaps still remain on how this vital microbial organ plays a role in orchestrating breast cancer development. Nevertheless, undeniable evidence from studies has pinpointed the presence of specific microbial elements of the breast and gut to play a role in governing breast cancer. It is still unclear if an alteration in microbiome/dysbiosis leads to breast cancer or is it vice versa. Though specific microbial signatures have been detected to be associated with various breast cancer subtypes, the structure and composition of a core "healthy" microbiome is yet to be established. Probiotics seem to be a promising antidote for targeted prevention and treatment of breast cancer. Interestingly, these microbial communities can serve as potential biomarkers for prognosis, diagnosis, and treatment of breast cancer, thereby leading to the rise of a completely new era of personalized medicine. This review is a humble attempt to summarize the research findings on the human microbiome and its relation to breast cancer.}, }
@article {pmid32714306, year = {2020}, author = {Spacova, I and Dodiya, HB and Happel, AU and Strain, C and Vandenheuvel, D and Wang, X and Reid, G}, title = {Future of Probiotics and Prebiotics and the Implications for Early Career Researchers.}, journal = {Frontiers in microbiology}, volume = {11}, number = {}, pages = {1400}, pmid = {32714306}, issn = {1664-302X}, abstract = {The opportunities in the fields of probiotics and prebiotics to a great degree stem from what we can learn about how they influence the microbiota and interact with the host. We discuss recent insights, cutting-edge technologies and controversial results from the perspective of early career researchers innovating in these areas. This perspective emerged from the 2019 meeting of the International Scientific Association for Probiotics and Prebiotics - Student and Fellows Association (ISAPP-SFA). Probiotic and prebiotic research is being driven by genetic characterization and modification of strains, state-of-the-art in vitro, in vivo, and in silico techniques designed to uncover the effects of probiotics and prebiotics on their targets, and metabolomic tools to identify key molecules that mediate benefits on the host. These research tools offer unprecedented insights into the functionality of probiotics and prebiotics in the host ecosystem. Young scientists need to acquire these diverse toolsets, or form inter-connected teams to perform comprehensive experiments and systematic analysis of data. This will be critical to identify microbial structure and co-dependencies at body sites and determine how administered probiotic strains and prebiotic substances influence the host. This and other strategies proposed in this review will pave the way for translating the health benefits observed during research into real-life outcomes. Probiotic strains and prebiotic products can contribute greatly to the amelioration of global issues threatening society. The intent of this article is to provide an early career researcher's perspective on where the biggest opportunities lie to advance science and impact human health.}, }
@article {pmid32708627, year = {2020}, author = {Garvey, M}, title = {Bacteriophages and the One Health Approach to Combat Multidrug Resistance: Is This the Way?.}, journal = {Antibiotics (Basel, Switzerland)}, volume = {9}, number = {7}, pages = {}, pmid = {32708627}, issn = {2079-6382}, abstract = {Antimicrobial resistance necessitates action to reduce and eliminate infectious disease, ensure animal and human health, and combat emerging diseases. Species such as Acinetobacter baumanniii, vancomycin resistant Enterococcus, methicillin resistance Staphylococcus aureus, and Pseudomonas aeruginosa, as well as other WHO priority pathogens, are becoming extremely difficult to treat. In 2017, the EU adopted the "One Health" approach to combat antibiotic resistance in animal and human medicine and to prevent the transmission of zoonotic disease. As the current therapeutic agents become increasingly inadequate, there is a dire need to establish novel methods of treatment under this One Health Framework. Bacteriophages (phages), viruses infecting bacterial species, demonstrate clear antimicrobial activity against an array of resistant species, with high levels of specificity and potency. Bacteriophages play key roles in bacterial evolution and are essential components of all ecosystems, including the human microbiome. Factors such are their specificity, potency, biocompatibility, and bactericidal activity make them desirable options as therapeutics. Issues remain, however, relating to their large-scale production, formulation, stability, and bacterial resistance, limiting their implementation globally. Phages used in therapy must be virulent, purified, and well characterized before administration. Clinical studies are warranted to assess the in vivo pharmacokinetics and pharmacodynamic characteristics of phages to fully establish their therapeutic potential.}, }
@article {pmid32706929, year = {2021}, author = {Wisgrill, L and Werner, P and Jalonen, E and Berger, A and Lauerma, A and Alenius, H and Fyhrquist, N}, title = {Integrative transcriptome analysis deciphers mechanisms of nickel contact dermatitis.}, journal = {Allergy}, volume = {76}, number = {3}, pages = {804-815}, pmid = {32706929}, issn = {1398-9995}, mesh = {*Dermatitis, Allergic Contact/genetics ; Gene Expression Profiling ; Humans ; *Nickel/adverse effects ; Patch Tests ; Quality of Life ; }, abstract = {BACKGROUND: Nickel-induced allergic contact dermatitis (nACD) remains a major occupational skin disorder, significantly impacting the quality of life of suffering patients. Complex cellular compositional changes and associated immunological pathways are partly resolved in humans; thus, the impact of nACD on human skin needs to be further elucidated.<br><br>METHODS: To decipher involved immunological players and pathways, human skin biopsies were taken at 0, 2, 48, and 96&#xa0;hours after nickel patch test in six nickel-allergic patients. Gene expression profiles were analyzed via microarray.<br><br>RESULTS: Leukocyte deconvolution of nACD-affected skin identified major leukocyte compositional changes at 48 and 96&#xa0;hours, including natural killer (NK) cells, macrophage polarization, and T-cell immunity. Gene set enrichment analysis mirrored cellular-linked functional pathways enriched over time. NK cell infiltration and cytotoxic pathways were uniquely found in nACD-affected skin compared to sodium lauryl sulfate-induced irritant skin reactions.<br><br>CONCLUSION: These results highlight key immunological leukocyte subsets as well as associated pathways in nACD, providing insights into pathophysiology with the potential to unravel novel therapeutic targets.}, }
@article {pmid32689930, year = {2020}, author = {Buongermino Pereira, M and Österlund, T and Eriksson, KM and Backhaus, T and Axelson-Fisk, M and Kristiansson, E}, title = {A comprehensive survey of integron-associated genes present in metagenomes.}, journal = {BMC genomics}, volume = {21}, number = {1}, pages = {495}, pmid = {32689930}, issn = {1471-2164}, mesh = {Bacteria/genetics ; Gene Transfer, Horizontal ; Genes, Bacterial ; Humans ; *Integrons/genetics ; *Metagenome ; }, abstract = {BACKGROUND: Integrons are genomic elements that mediate horizontal gene transfer by inserting and removing genetic material using site-specific recombination. Integrons are commonly found in bacterial genomes, where they maintain a large and diverse set of genes that plays an important role in adaptation and evolution. Previous studies have started to characterize the wide range of biological functions present in integrons. However, the efforts have so far mainly been limited to genomes from cultivable bacteria and amplicons generated by PCR, thus targeting only a small part of the total integron diversity. Metagenomic data, generated by direct sequencing of environmental and clinical samples, provides a more holistic and unbiased analysis of integron-associated genes. However, the fragmented nature of metagenomic data has previously made such analysis highly challenging.<br><br>RESULTS: Here, we present a systematic survey of integron-associated genes in metagenomic data. The analysis was based on a newly developed computational method where integron-associated genes were identified by detecting their associated recombination sites. By processing contiguous sequences assembled from more than 10 terabases of metagenomic data, we were able to identify 13,397 unique integron-associated genes. Metagenomes from marine microbial communities had the highest occurrence of integron-associated genes with levels more than 100-fold higher than in the human microbiome. The identified genes had a large functional diversity spanning over several functional classes. Genes associated with defense mechanisms and mobility facilitators were most overrepresented and more than five times as common in integrons compared to other bacterial genes. As many as two thirds of the genes were found to encode proteins of unknown function. Less than 1% of the genes were associated with antibiotic resistance, of which several were novel, previously undescribed, resistance gene variants.<br><br>CONCLUSIONS: Our results highlight the large functional diversity maintained by integrons present in unculturable bacteria and significantly expands the number of described integron-associated genes.}, }
@article {pmid32687052, year = {2020}, author = {Descheemaeker, L and de Buyl, S}, title = {Stochastic logistic models reproduce experimental time series of microbial communities.}, journal = {eLife}, volume = {9}, number = {}, pages = {}, pmid = {32687052}, issn = {2050-084X}, support = {SRP31//Vrije Universiteit Brussel/International ; }, mesh = {Logistic Models ; *Microbiota ; *Models, Biological ; Population Dynamics ; Stochastic Processes ; }, abstract = {We analyze properties of experimental microbial time series, from plankton and the human microbiome, and investigate whether stochastic generalized Lotka-Volterra models could reproduce those properties. We show that this is the case when the noise term is large and a linear function of the species abundance, while the strength of the self-interactions varies over multiple orders of magnitude. We stress the fact that all the observed stochastic properties can be obtained from a logistic model, that is, without interactions, even the niche character of the experimental time series. Linear noise is associated with growth rate stochasticity, which is related to changes in the environment. This suggests that fluctuations in the sparsely sampled experimental time series may be caused by extrinsic sources.}, }
@article {pmid32684275, year = {2020}, author = {Joseph, TA and Pasarkar, AP and Pe'er, I}, title = {Efficient and Accurate Inference of Mixed Microbial Population Trajectories from Longitudinal Count Data.}, journal = {Cell systems}, volume = {10}, number = {6}, pages = {463-469.e6}, doi = {10.1016/j.cels.2020.05.006}, pmid = {32684275}, issn = {2405-4720}, mesh = {Data Analysis ; Humans ; Longitudinal Studies ; Microbiota/*physiology ; Research Design ; }, abstract = {The recently completed second phase of the Human Microbiome Project has highlighted the relationship between dynamic changes in the microbiome and disease, motivating new microbiome study designs based on longitudinal sampling. Yet, analysis of such data is hindered by presence of technical noise, high dimensionality, and data sparsity. Here, we introduce LUMINATE (longitudinal microbiome inference and zero detection), a fast and accurate method for inferring relative abundances from noisy read count data. We demonstrate that LUMINATE is orders of magnitude faster than current approaches, with better or similar accuracy. We further show that LUMINATE can accurately distinguish biological zeros, when a taxon is absent from the community, from technical zeros, when a taxon is below the detection threshold. We conclude by demonstrating the utility of LUMINATE on a real dataset, showing that LUMINATE smooths trajectories observed from noisy data. LUMINATE is freely available from https://github.com/tyjo/luminate.}, }
@article {pmid32680791, year = {2020}, author = {Daisley, BA and Chmiel, JA and Pitek, AP and Thompson, GJ and Reid, G}, title = {Missing Microbes in Bees: How Systematic Depletion of Key Symbionts Erodes Immunity.}, journal = {Trends in microbiology}, volume = {28}, number = {12}, pages = {1010-1021}, doi = {10.1016/j.tim.2020.06.006}, pmid = {32680791}, issn = {1878-4380}, mesh = {Animals ; Bees/*immunology/*microbiology ; Disease Resistance/physiology ; Ecology ; Host Microbial Interactions/*physiology ; *Immunity ; Lactobacillus ; Microbiota ; Nutrients/deficiency ; Pesticides/pharmacology ; Probiotics ; Stress, Physiological ; Symbiosis ; }, abstract = {Pesticide exposure, infectious disease, and nutritional stress contribute to honey bee mortality and a high rate of colony loss. This realization has fueled a decades-long investigation into the single and combined effects of each stressor and their overall bearing on insect physiology. However, one element largely missing from this research effort has been the evaluation of underlying microbial communities in resisting environmental stressors and their influence on host immunity and disease tolerance. In humans, multigenerational bombardment by antibiotics is linked with many contemporary diseases. Here, we draw a parallel conclusion for the case in honey bees and suggest that chronic exposure to antimicrobial xenobiotics can systematically deplete honey bees of their microbes and hamper cross-generational preservation of host-adapted symbionts that are crucial to health.}, }
@article {pmid32679247, year = {2020}, author = {Le, ST and Toussi, A and Maverakis, N and Marusina, AI and Barton, VR and Merleev, AA and Luxardi, G and Raychaudhuri, SP and Maverakis, E}, title = {The cutaneous and intestinal microbiome in psoriatic disease.}, journal = {Clinical immunology (Orlando, Fla.)}, volume = {218}, number = {}, pages = {108537}, doi = {10.1016/j.clim.2020.108537}, pmid = {32679247}, issn = {1521-7035}, mesh = {Animals ; Gastrointestinal Tract/*microbiology ; Humans ; *Microbiota ; Psoriasis/*microbiology ; Skin/*microbiology ; }, abstract = {Psoriasis (PsO) and psoriatic arthritis (PsA) are chronic immune-mediated inflammatory diseases of multifactorial etiology. In addition to genetic and environmental factors, evidence supports involvement of a dysregulated human microbiome in the pathogenesis of psoriatic disease. In particular, alterations in the composition of the microbiome, termed dysbiosis, can result in downstream proinflammatory effects in the gut, skin, and joints. Both the cutaneous and intestinal microbial populations are implicated in the pathogenesis of psoriatic disease, although exact mechanisms are unclear. Herein, we review the relationship between the human microbiome and psoriatic disease. Further insight into the functions of the microbiome may allow for greater understanding of inflammatory disease processes and identification of additional therapeutic targets.}, }
@article {pmid32677447, year = {2020}, author = {Gao, W and Baumgartel, KL and Alexander, SA}, title = {The Gut Microbiome as a Component of the Gut-Brain Axis in Cognitive Health.}, journal = {Biological research for nursing}, volume = {22}, number = {4}, pages = {485-494}, pmid = {32677447}, issn = {1552-4175}, support = {T32 NR009759/NR/NINR NIH HHS/United States ; }, mesh = {Brain/*physiology ; Cognition/*physiology ; Cognitive Dysfunction/*physiopathology ; Dysbiosis/physiopathology ; Gastrointestinal Microbiome/*physiology ; Humans ; Nursing Research ; }, abstract = {INTRODUCTION: The human microbiome, the microorganisms living in and on the body, plays a vital role in brain physiology and pathophysiology. The gut microbiome (GMB) has been identified as a link in the gut-brain axis moderating cognitive development and health.<br><br>OBJECTIVES: The objectives of this scoping review are to discuss mechanisms of the microbiome-gut-brain axis in cognition, review the existing literature on the GMB and cognition, and discuss implications for nursing research.<br><br>METHODS: We searched Pubmed using the terms "gut microbiome," "brain," and "cognition" and the terms "gut brain axis," "microbiome," and "cognition"; removed duplicates, studies not published in English, and unrelated publications; and added additional articles identified through references. We retained the 85 most relevant publications for this review.<br><br>RESULTS: Common themes in the current literature include GMB components; interactions on cognitive development; effects of GMB-gut-brain interactions on cognition, mild cognitive impairment and Alzheimer's disease; effects of GMB interactions with physiologic stress on cognition in critical care; and GMB modification for improved cognition. Review of the literature on each of these topics reveals multiple theoretical mechanisms of action for GMB-gut-brain interaction that modify cognitive development and function across the lifespan.<br><br>DISCUSSION: GMB components and dysbiosis have been implicated in many cognitive states, and specific microbiota constituents contribute to cognitive development, stability, and impairment. The study of these interactions is relevant to nursing research as it addresses the holistic human experience and microbiome constituents are modifiable, facilitating translation into the clinical setting.}, }
@article {pmid32675857, year = {2020}, author = {Dupont, HL and Jiang, ZD and Dupont, AW and Utay, NS}, title = {THE INTESTINAL MICROBIOME IN HUMAN HEALTH AND DISEASE.}, journal = {Transactions of the American Clinical and Climatological Association}, volume = {131}, number = {}, pages = {178-197}, pmid = {32675857}, issn = {0065-7778}, support = {P30 DK056338/DK/NIDDK NIH HHS/United States ; }, abstract = {The Human Microbiome Initiative of NIH, begun in 2007, has opened the door to the power of the intestinal microbiome in health and disease. The 100 trillion gut microbes influence body function through three pathways: (1) via the neural route where 500 million neurons of the enteric nervous system (the body's second brain) connect to the brain and spinal cord, (2) via the immune route where the gut-immune capacity prevents infection and elicits immune response to vaccines, and (3) by the hormonal route wherein biologically active chemicals are released from enteroendocrine cells to control mood and body functions. Through research, the identification of diseases and disorders associated with abnormal microbiome ("dysbiosis") has increased in number with potential for reversibility. Our team has developed an orally administered fecal microbiota transplantation product that is effective in reversing dysbiosis in recurrent Clostridioides difficile (C. difficile) and is being used to reverse abnormal microbiomes in chronic dysbiotic disorders.}, }
@article {pmid32673603, year = {2020}, author = {Giannoni, E and Baud, D and Agri, VD and Gibson, GR and Reid, G}, title = {Probiotics and COVID-19.}, journal = {The lancet. Gastroenterology &amp; hepatology}, volume = {5}, number = {8}, pages = {720-721}, pmid = {32673603}, issn = {2468-1253}, mesh = {*Betacoronavirus ; COVID-19 ; *Coronavirus Infections ; Humans ; *Pandemics ; *Pneumonia, Viral ; *Probiotics ; SARS-CoV-2 ; }, }
@article {pmid32670603, year = {2020}, author = {Hadrich, D}, title = {New EU projects delivering human microbiome applications.}, journal = {Future science OA}, volume = {6}, number = {6}, pages = {FSO474}, pmid = {32670603}, issn = {2056-5623}, abstract = {Over recent years, the number of studies and projects showing correlations between the human microbiome and diseases has increased enormously. The potential of the human microbiome for healthcare is big. However, many confounders have been discovered and the relevant disease mechanisms and the causalities of these diseases still require more efforts and better understanding. The EU called for project proposals exploiting the application potential of human microbiome research and finally decided to fund the three top excellent new H2020 projects ONCOBIOME, MICROB-PREDICT and GEMMA. They get a total EU funding of €44 M and started in January 2019 with the aim to deliver high impact through validated clinical tools that are helpful for end-users.}, }
@article {pmid32668369, year = {2020}, author = {Matenchuk, BA and Mandhane, PJ and Kozyrskyj, AL}, title = {Sleep, circadian rhythm, and gut microbiota.}, journal = {Sleep medicine reviews}, volume = {53}, number = {}, pages = {101340}, doi = {10.1016/j.smrv.2020.101340}, pmid = {32668369}, issn = {1532-2955}, mesh = {Animals ; Circadian Rhythm/*physiology ; Diet ; Feeding Behavior/physiology ; Gastrointestinal Microbiome/*physiology ; Humans ; Mice ; Sleep/*physiology ; Sleep Deprivation/*physiopathology ; }, abstract = {From asthma and heart disease to diabetes and obesity, the human microbiome plays a role in the pathogenesis of each chronic health condition plaguing today's society. Recent work has shown that the gut microbiota and its metabolites exhibit diurnal rhythmicity which predominantly respond to the feeding/fasting cycle. Persistent jet lag, an obesogenic diet, and clock gene deficiency can dampen the oscillatory nature of gut bacterial composition, which can subsequently be rescued by time restricted feeding. Contrastingly, gut microbial metabolites influence central and hepatic clock gene expression and sleep duration in the host and regulate body composition through circadian transcription factors. Both sleep fragmentation and short sleep duration are associated with gut dysbiosis which may be due to activation of the HPA-axis. Metabolic disturbances associated with sleep loss may in fact be mediated through the overgrowth of specific gut bacteria. Reciprocally, the end products of bacterial species which grow in response to sleep loss are able to induce fatigue. Furthermore, probiotic supplementation has been found to improve subjective sleep quality. Sleep quality and duration may be an important target for supporting healthy gut microbiota composition, but the cyclic nature of this relationship should not be overlooked.}, }
@article {pmid32665329, year = {2020}, author = {Zhao, C and Wei, Z and Yang, J and Zhang, J and Yu, C and Yang, A and Zhang, M and Zhang, L and Wang, Y and Mu, X and Heng, X and Yang, H and Gai, Z and Wang, X and Zhang, L}, title = {Characterization of the Vaginal Microbiome in Women with Infertility and Its Potential Correlation with Hormone Stimulation during In Vitro Fertilization Surgery.}, journal = {mSystems}, volume = {5}, number = {4}, pages = {}, pmid = {32665329}, issn = {2379-5077}, abstract = {Perturbation of vaginal microbiome of reproductive-age women influences all the phases of a woman's reproductive life. Although studies have shown that dynamic changes in vaginal microbiome can affect pregnancy, its role in secondary infertility (i.e., inability to become pregnant or to carry a pregnancy successfully after previous success in delivering a child) and in vitro fertilization (IVF) remains to be unraveled. To determine the vaginal microbiome in women undergoing in vitro fertilization and embryo transfer (IVF-ET) and investigate its potential correlations with hormone stimulation, we recruited 30 patients with secondary infertility and receiving IVF and 92 matched healthy women and analyzed their vaginal microbiome composition using 16S rRNA gene sequencing. Our results show that women suffering from infertility (infertile women) exhibit a significant decrease in microbiome diversity and richness compared with healthy women during the nonovulation period (follicular phase) (P < 0.01), whereas vaginal microbiome of healthy women reveals dramatic fluctuations during ovulation (P < 0.05). Interestingly, infertility patients show no change of the vaginal microbiome under conditions of gonadotropin-releasing hormone (GnRH) agonist and recombinant human chorionic gonadotropin (r-hCG) induction (P > 0.05). Moreover, our results indicate that infertile women show characteristic variations in vaginal microbiome, such as increased abundance of Atopobium, Aerococcus, and Bifidobacterium and decreased abundance of Lactobacillus and Leuconostoc IMPORTANCE The microbiome had been hypothesized to be involved in the physiology and pathophysiology of assisted reproduction before the first success in IVF, while the data supporting or refuting this hypothesis were less than conclusive. Thanks to sequencing data from the 16S rRNA subunit, we characterized the microbiome in the reproductive tract of infertile women, and we found that changes in the vaginal microbiome are related to female infertility. We also found that the characteristic microbiome bacteria are mainly members of several genera and that the vaginal microbiome of infertile women is not sensitive to hormonal changes during IVF. In conclusion, our report provides data that can be used for discovering the role of the vaginal microbiome in patients suffering from secondary infertility.}, }
@article {pmid32663769, year = {2020}, author = {Arnolds, KL and Martin, CG and Lozupone, CA}, title = {Blood type and the microbiome- untangling a complex relationship with lessons from pathogens.}, journal = {Current opinion in microbiology}, volume = {56}, number = {}, pages = {59-66}, pmid = {32663769}, issn = {1879-0364}, support = {T32 AI007405/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Bacteria/classification/genetics/*isolation &amp; purification ; Bacterial Infections/*genetics/immunology/microbiology ; Bacterial Physiological Phenomena ; Blood Group Antigens/*genetics/immunology ; Humans ; *Microbiota ; *Symbiosis ; }, abstract = {The complex communities of microbes that constitute the human microbiome are influenced by host and environmental factors. Here, we address how a fundamental aspect of human biology, blood type, contributes to shaping this microscopic ecosystem. Although this question remains largely unexplored, we glean insights from decades of work describing relationships between pathogens and blood type. The bacterial strategies, molecular mechanisms, and host responses that shaped those relationships may parallel those that characterize how blood type and commensals interact. Understanding these nuanced interactions will expand our capacity to analyze and manipulate the human microbiome.}, }
@article {pmid32660471, year = {2020}, author = {Koslovsky, MD and Vannucci, M}, title = {MicroBVS: Dirichlet-tree multinomial regression models with Bayesian variable selection - an R package.}, journal = {BMC bioinformatics}, volume = {21}, number = {1}, pages = {301}, pmid = {32660471}, issn = {1471-2105}, mesh = {Algorithms ; Bacteroides/classification ; *Bayes Theorem ; Diet ; Humans ; Microbiota ; Phylogeny ; Prevotella/classification ; *Software ; }, abstract = {BACKGROUND: Understanding the relation between the human microbiome and modulating factors, such as diet, may help researchers design intervention strategies that promote and maintain healthy microbial communities. Numerous analytical tools are available to help identify these relations, oftentimes via automated variable selection methods. However, available tools frequently ignore evolutionary relations among microbial taxa, potential relations between modulating factors, as well as model selection uncertainty.<br><br>RESULTS: We present MicroBVS, an R package for Dirichlet-tree multinomial models with Bayesian variable selection, for the identification of covariates associated with microbial taxa abundance data. The underlying Bayesian model accommodates phylogenetic structure in the abundance data and various parameterizations of covariates' prior probabilities of inclusion.<br><br>CONCLUSION: While developed to study the human microbiome, our software can be employed in various research applications, where the aim is to generate insights into the relations between a set of covariates and compositional data with or without a known tree-like structure.}, }
@article {pmid32660414, year = {2020}, author = {Huh, JW and Roh, TY}, title = {Opportunistic detection of Fusobacterium nucleatum as a marker for the early gut microbial dysbiosis.}, journal = {BMC microbiology}, volume = {20}, number = {1}, pages = {208}, pmid = {32660414}, issn = {1471-2180}, support = {NRF-2014M3C9A3064548, NRF-2017M3C9A6047625//National Research Foundation of Korea/International ; 10Z20130012243//Ministry of Education/International ; S2632274//Technology Development Program of MSS, Republic of Korea/International ; }, mesh = {Bacteria/*classification/isolation &amp; purification ; Discriminant Analysis ; Dysbiosis/*diagnosis ; Feces/microbiology ; Female ; Fusobacterium nucleatum/*isolation &amp; purification ; Gastrointestinal Microbiome ; Humans ; Inflammatory Bowel Diseases/*microbiology ; Logistic Models ; Longitudinal Studies ; Male ; Phylogeny ; }, abstract = {BACKGROUND: The essential roles of gut microbiome have been emphasized in modulating human health and disease. Fusobacterium nucleatum (F. nucleatum), an obligate Gram-negative microorganism residing in oral cavity, gastrointestinal tract and elsewhere, has been recently considered as a potential oncobacterium associated with human cancers. However, the consequence of its enrichment was not extensively explored in terms of microbial homeostasis and stability at the early stage of disease development.<br><br>RESULT: Our analysis on longitudinal metagenomic data generated by the Integrative Human Microbiome Project (iHMP) showed that F. nucleatum was frequently found in inflammatory bowel diseases (IBD) subjects with reduced microbial diversity. Using non-parametric logarithmic linear discriminant analysis (LDA) effect size (LEfSe) algorithm, 12 IBD- and 14 non-IBD-specific bacterial species were identified in the fecal metagenome and the IBD-specific ones were over-represented in the F. nucleatum-experienced subjects during long-term surveillance. In addition, F. nucleatum experience severely abrogated intra-personal stability of microbiome in IBD patients and induced highly variable gut microbiome between subjects. From the longitudinal comparison between microbial distributions prior and posterior to F. nucleatum detection, 41 species could be proposed as indicative "classifiers" for dysbiotic gut state. By multiple logistic regression models established on these classifiers, the high probability of experiencing F. nucleatum was significantly correlated with decreased alpha-diversity and increased number of biomarker species for IBD and colorectal cancer (CRC). Finally, microbial clustering confirmed that biomarker species for IBD and non-IBD conditions as well as CRC signature markers were well distinguishable and could be utilized for explaining gut symbiosis and dysbiosis.<br><br>CONCLUSION: F. nucleatum opportunistically appeared under early dysbiotic condition in gut, and discriminative classifier species associated with F. nucleatum were successfully applied to predict microbial alterations in both IBD and non-IBD conditions. Our prediction model and microbial classifier biomarkers for estimating gut dysbiosis should provide a novel aspect of microbial homeostasis/dynamics and useful information on non-invasive biomarker screening.}, }
@article {pmid32658296, year = {2020}, author = {Sutherland, VL and McQueen, CA and Mendrick, D and Gulezian, D and Cerniglia, C and Foley, S and Forry, S and Khare, S and Liang, X and Manautou, JE and Tweedie, D and Young, H and Alekseyenko, AV and Burns, F and Dietert, R and Wilson, A and Chen, C}, title = {The Gut Microbiome and Xenobiotics: Identifying Knowledge Gaps.}, journal = {Toxicological sciences : an official journal of the Society of Toxicology}, volume = {176}, number = {1}, pages = {1-10}, pmid = {32658296}, issn = {1096-0929}, mesh = {Biomarkers ; Gastrointestinal Microbiome/*drug effects ; Humans ; Microbiota ; Xenobiotics/*toxicity ; }, abstract = {There is an increasing awareness that the gut microbiome plays a critical role in human health and disease, but mechanistic insights are often lacking. In June 2018, the Health and Environmental Sciences Institute (HESI) held a workshop, "The Gut Microbiome: Markers of Human Health, Drug Efficacy and Xenobiotic Toxicity" (https://hesiglobal.org/event/the-gut-microbiome-workshop) to identify data gaps in determining how gut microbiome alterations may affect human health. Speakers and stakeholders from academia, government, and industry addressed multiple topics including the current science on the gut microbiome, endogenous and exogenous metabolites, biomarkers, and model systems. The workshop presentations and breakout group discussions formed the basis for identifying data gaps and research needs. Two critical issues that emerged were defining the microbial composition and function related to health and developing standards for models, methods and analysis in order to increase the ability to compare and replicate studies. A series of key recommendations were formulated to focus efforts to further understand host-microbiome interactions and the consequences of exposure to xenobiotics as well as identifying biomarkers of microbiome-associated disease and toxicity.}, }
@article {pmid32656839, year = {2020}, author = {Lahtinen, P and Jalanka, J and Hartikainen, A and Mattila, E and Hillilä, M and Punkkinen, J and Koskenpato, J and Anttila, VJ and Tillonen, J and Satokari, R and Arkkila, P}, title = {Letter: faecal microbiota transplantation for irritable bowel syndrome. Authors' reply.}, journal = {Alimentary pharmacology &amp; therapeutics}, volume = {52}, number = {3}, pages = {557-558}, doi = {10.1111/apt.15875}, pmid = {32656839}, issn = {1365-2036}, mesh = {*Anemia ; Azathioprine ; Fecal Microbiota Transplantation ; Humans ; *Irritable Bowel Syndrome ; *Leukopenia ; }, }
@article {pmid32654186, year = {2021}, author = {Cavaleiro Rufo, J and Paciência, I and Hoffimann, E and Moreira, A and Barros, H and Ribeiro, AI}, title = {The neighbourhood natural environment is associated with asthma in children: A birth cohort study.}, journal = {Allergy}, volume = {76}, number = {1}, pages = {348-358}, doi = {10.1111/all.14493}, pmid = {32654186}, issn = {1398-9995}, mesh = {*Asthma/epidemiology/etiology ; Child ; Child, Preschool ; Cohort Studies ; Environment ; Female ; Humans ; Infant, Newborn ; Longitudinal Studies ; Portugal/epidemiology ; Pregnancy ; }, abstract = {BACKGROUND: A lower exposure to the natural environment has been hypothesized to adversely affect the human microbiome and its immunomodulatory capacity. However, the underlying effects of this hypothesis are still not understood. We aimed to evaluate the effect of early-life exposure to greenness and species richness on the development of allergic diseases and asthma in children.<br><br>METHODS: A longitudinal study was conducted comprising 1050 children from a population-based birth cohort recruited in Portugal. Residential normalized difference vegetation index (NDVI) and species richness index (SRI) were assessed at baseline to estimate their association with allergic diseases and asthma at the ages of 4 and 7.<br><br>RESULTS: Significant predisposing associations were observed between the exposure to species richness at baseline and the onset of asthma and wheezing at the age of 7. Children living in neighbourhoods surrounded by high levels of SRI were at a significantly higher risk developing allergic sensitization(OR [95% CI]&#xa0;=&#xa0;2.00 [1.04:3.86] at age 4; 2.35 [1.20:4.63] at age 7). Living surrounded by greener environments was significantly associated with a lower prevalence of asthma and rhinitis at the age of 7(0.41 [0.18:0.97] and 0.37 [0.15:0.93], respectively).<br><br>CONCLUSIONS: Living in close proximity to a greener environment at birth has a protective effect on the development of allergic diseases and asthma at the age of 7. Conversely, living in neighbourhoods with a high number of fauna species appears to be associated with a higher risk for allergy, asthma and wheezing.}, }
@article {pmid32647884, year = {2020}, author = {Wiley, CA}, title = {Emergent Viral Infections of the CNS.}, journal = {Journal of neuropathology and experimental neurology}, volume = {79}, number = {8}, pages = {823-842}, doi = {10.1093/jnen/nlaa054}, pmid = {32647884}, issn = {1554-6578}, mesh = {Animals ; Birds ; Central Nervous System Viral Diseases/*epidemiology/prevention &amp; control/*transmission ; Ecosystem ; Humans ; Influenza in Birds/epidemiology/prevention &amp; control/transmission ; Influenza, Human/epidemiology/prevention &amp; control/transmission ; West Nile Fever/epidemiology/prevention &amp; control/transmission ; Zika Virus Infection/epidemiology/prevention &amp; control/transmission ; Zoonoses/*epidemiology/prevention &amp; control/*transmission ; }, abstract = {Biological evolution of the microbiome continually drives the emergence of human viral pathogens, a subset of which attack the nervous system. The sheer number of pathogens that have appeared, along with their abundance in the environment, demand our attention. For the most part, our innate and adaptive immune systems have successfully protected us from infection; however, in the past 5 decades, through pathogen mutation and ecosystem disruption, a dozen viruses emerged to cause significant neurologic disease. Most of these pathogens have come from sylvatic reservoirs having made the energetically difficult, and fortuitously rare, jump into humans. But the human microbiome is also replete with agents already adapted to the host that need only minor mutations to create neurotropic/toxic agents. While each host/virus symbiosis is unique, this review examines virologic and immunologic principles that govern the pathogenesis of different viral CNS infections that were described in the past 50 years (Influenza, West Nile Virus, Zika, Rift Valley Fever Virus, Hendra/Nipah, Enterovirus-A71/-D68, Human parechovirus, HIV, and SARS-CoV). Knowledge of these pathogens provides us the opportunity to respond and mitigate infection while at the same time prepare for inevitable arrival of unknown agents.}, }
@article {pmid32636826, year = {2020}, author = {Filik, K and Szermer-Olearnik, B and Wernecki, M and Happonen, LJ and Pajunen, MI and Nawaz, A and Qasim, MS and Jun, JW and Mattinen, L and Skurnik, M and Brzozowska, E}, title = {The Podovirus ϕ80-18 Targets the Pathogenic American Biotype 1B Strains of Yersinia enterocolitica.}, journal = {Frontiers in microbiology}, volume = {11}, number = {}, pages = {1356}, pmid = {32636826}, issn = {1664-302X}, abstract = {We report here the complete genome sequence and characterization of Yersinia bacteriophage vB_YenP_ϕ80-18. ϕ80-18 was isolated in 1991 using a Y. enterocolitica serotype O:8 strain 8081 as a host from a sewage sample in Turku, Finland, and based on its morphological and genomic features is classified as a podovirus. The genome is 42 kb in size and has 325 bp direct terminal repeats characteristic for podoviruses. The genome contains 57 predicted genes, all encoded in the forward strand, of which 29 showed no similarity to any known genes. Phage particle proteome analysis identified altogether 24 phage particle-associated proteins (PPAPs) including those identified as structural proteins such as major capsid, scaffolding and tail component proteins. In addition, also the DNA helicase, DNA ligase, DNA polymerase, 5'-exonuclease, and the lytic glycosylase proteins were identified as PPAPs, suggesting that they might be injected together with the phage genome into the host cell to facilitate the take-over of the host metabolism. The phage-encoded RNA-polymerase and DNA-primase were not among the PPAPs. Promoter search predicted the presence of four phage and eleven host RNA polymerase -specific promoters in the genome, suggesting that early transcription of the phage is host RNA-polymerase dependent and that the phage RNA polymerase takes over later. The phage tolerates pH values between 2 and 12, and is stable at 50°C but is inactivated at 60°C. It grows slowly with a 50 min latent period and has apparently a low burst size. Electron microscopy revealed that the phage has a head diameter of about 60 nm, and a short tail of 20 nm. Whole-genome phylogenetic analysis confirmed that ϕ80-18 belongs to the Autographivirinae subfamily of the Podoviridae family, that it is 93.2% identical to Yersinia phage fHe-Yen3-01. Host range analysis showed that ϕ80-18 can infect in addition to Y. enterocolitica serotype O:8 strains also strains of serotypes O:4, O:4,32, O:20 and O:21, the latter ones representing similar to Y. enterocolitica serotype O:8, the American pathogenic biotype 1B strains. In conclusion, the phage ϕ80-18 is a promising candidate for the biocontrol of the American biotype 1B Y. enterocolitica.}, }
@article {pmid32635461, year = {2020}, author = {Puccetti, M and Xiroudaki, S and Ricci, M and Giovagnoli, S}, title = {Postbiotic-Enabled Targeting of the Host-Microbiota-Pathogen Interface: Hints of Antibiotic Decline?.}, journal = {Pharmaceutics}, volume = {12}, number = {7}, pages = {}, pmid = {32635461}, issn = {1999-4923}, support = {FFC#24/2018//Fondazione per la Ricerca sulla Fibrosi Cistica/ ; }, abstract = {Mismanagement of bacterial infection therapies has undermined the reliability and efficacy of antibiotic treatments, producing a profound crisis of the antibiotic drug market. It is by now clear that tackling deadly infections demands novel strategies not only based on the mere toxicity of anti-infective compounds. Host-directed therapies have been the first example as novel treatments with alternate success. Nevertheless, recent advances in the human microbiome research have provided evidence that compounds produced by the microbial metabolism, namely postbiotics, can have significant impact on human health. Such compounds target the host-microbe-pathogen interface rescuing biotic and immune unbalances as well as inflammation, thus providing novel therapeutic opportunities. This work discusses critically, through literature review and personal contributions, these novel nonantibiotic treatment strategies for infectious disease management and resistance prevention, which could represent a paradigm change rocking the foundation of current antibiotic therapy tenets.}, }
@article {pmid32634783, year = {2020}, author = {Yang, Y and Liu, S and Wang, Y and Wang, Z and Ding, W and Sun, X and He, K and Feng, Q and Zhang, X}, title = {Changes of saliva microbiota in the onset and after the treatment of diabetes in patients with periodontitis.}, journal = {Aging}, volume = {12}, number = {13}, pages = {13090-13114}, pmid = {32634783}, issn = {1945-4589}, mesh = {Cohort Studies ; DNA, Bacterial/classification/genetics ; *Diabetes Mellitus, Type 2/complications/drug therapy ; Gastrointestinal Microbiome/*genetics ; Humans ; Hypoglycemic Agents/therapeutic use ; Periodontitis/*complications ; Saliva/*microbiology ; }, abstract = {The relationship between type 2 diabetes mellitus (T2DM) and oral microbiota is still insufficiently recognized. In the present study, we compared the salivary microbiome of nondiabetic individuals, treatment-naïve diabetic patients, and diabetic patients treated with metformin or a combination of insulin and other drugs. The α- and β-diversity demonstrated significant differences in the salivary microbiome between the nondiabetic people and patients with a history of diabetes, while little divergence was found among individuals with a history of diabetes. After characterizing the effects of periodontitis on the microbial composition of each group, the salivary microbiome of the treatment-naïve diabetic patient group was compared with that of nondiabetic people and the metformin/combined treatment groups. The results revealed changes in the contents of certain bacteria after both the onset and the treatment of diabetes; among these differential bacteria, Blautia_wexlerae, Lactobacillus_fermentum, Nocardia_coeliaca and Selenomonas_artemidis varied in all processes. A subsequent correlational analysis of the differential bacteria and clinical characteristics demonstrated that salivary microbes were related to drug treatment and certain pathological changes. Finally, the four common differential bacteria were employed for distinguishing the treatment-naïve diabetic patients from the nondiabetic people and the treated patients, with prediction accuracies of 83.3%, 75% and 75%, respectively.}, }
@article {pmid32620549, year = {2020}, author = {Ianiro, G and Mullish, BH and Kelly, CR and Kassam, Z and Kuijper, EJ and Ng, SC and Iqbal, TH and Allegretti, JR and Bibbò, S and Sokol, H and Zhang, F and Fischer, M and Costello, SP and Keller, JJ and Masucci, L and van Prehn, J and Quaranta, G and Quraishi, MN and Segal, J and Kao, D and Satokari, R and Sanguinetti, M and Tilg, H and Gasbarrini, A and Cammarota, G}, title = {Reorganisation of faecal microbiota transplant services during the COVID-19 pandemic.}, journal = {Gut}, volume = {69}, number = {9}, pages = {1555-1563}, pmid = {32620549}, issn = {1468-3288}, mesh = {Betacoronavirus ; COVID-19 ; Change Management ; Clostridium Infections/microbiology/*therapy ; *Coronavirus Infections/epidemiology/prevention &amp; control ; *Donor Selection ; Fecal Microbiota Transplantation/*methods ; *Gastroenterology/organization &amp; administration/trends ; Gastrointestinal Microbiome ; Humans ; Infection Control/methods/standards ; *Pandemics/prevention &amp; control ; *Patient Selection ; *Pneumonia, Viral/epidemiology/prevention &amp; control ; Risk Adjustment/methods/standards ; SARS-CoV-2 ; }, abstract = {The COVID-19 pandemic has led to an exponential increase in SARS-CoV-2 infections and associated deaths, and represents a significant challenge to healthcare professionals and facilities. Individual countries have taken several prevention and containment actions to control the spread of infection, including measures to guarantee safety of both healthcare professionals and patients who are at increased risk of infection from COVID-19. Faecal microbiota transplantation (FMT) has a well-established role in the treatment of Clostridioides difficile infection. In the time of the pandemic, FMT centres and stool banks are required to adopt a workflow that continues to ensure reliable patient access to FMT while maintaining safety and quality of procedures. In this position paper, based on the best available evidence, worldwide FMT experts provide guidance on issues relating to the impact of COVID-19 on FMT, including patient selection, donor recruitment and selection, stool manufacturing, FMT procedures, patient follow-up and research activities.}, }
@article {pmid32620143, year = {2020}, author = {Creswell, R and Tan, J and Leff, JW and Brooks, B and Mahowald, MA and Thieroff-Ekerdt, R and Gerber, GK}, title = {High-resolution temporal profiling of the human gut microbiome reveals consistent and cascading alterations in response to dietary glycans.}, journal = {Genome medicine}, volume = {12}, number = {1}, pages = {59}, pmid = {32620143}, issn = {1756-994X}, support = {R01 GM130777/GM/NIGMS NIH HHS/United States ; 1R01GM130777/GM/NIGMS NIH HHS/United States ; }, mesh = {Algorithms ; Bayes Theorem ; Biodiversity ; Computational Biology/methods ; *Diet ; Feces/microbiology ; *Gastrointestinal Microbiome ; Healthy Volunteers ; Humans ; *Metagenome ; *Metagenomics/methods ; Models, Theoretical ; Polysaccharides/*metabolism ; Software ; }, abstract = {BACKGROUND: Dietary glycans, widely used as food ingredients and not directly digested by humans, are of intense interest for their beneficial roles in human health through shaping the microbiome. Characterizing the consistency and temporal responses of the gut microbiome to glycans is critical for rationally developing and deploying these compounds as therapeutics.<br><br>METHODS: We investigated the effect of two chemically distinct glycans (fructooligosaccharides and polydextrose) through three clinical studies conducted with 80 healthy volunteers. Stool samples, collected at dense temporal resolution (~&#x2009;4 times per week over 10&#x2009;weeks) and analyzed using shotgun metagenomic sequencing, enabled detailed characterization of participants' microbiomes. For analyzing the microbiome time-series data, we developed MC-TIMME2 (Microbial Counts Trajectories Infinite Mixture Model Engine 2.0), a purpose-built computational tool based on nonparametric Bayesian methods that infer temporal patterns induced by perturbations and groups of microbes sharing these patterns.<br><br>RESULTS: Overall microbiome structure as well as individual taxa showed rapid, consistent, and durable alterations across participants, regardless of compound dose or the order in which glycans were consumed. Significant changes also occurred in the abundances of microbial carbohydrate utilization genes in response to polydextrose, but not in response to fructooligosaccharides. Using MC-TIMME2, we produced detailed, high-resolution temporal maps of the microbiota in response to glycans within and across microbiomes.<br><br>CONCLUSIONS: Our findings indicate that dietary glycans cause reproducible, dynamic, and differential alterations to the community structure of the human microbiome.}, }
@article {pmid32615913, year = {2020}, author = {Ames, NJ and Barb, JJ and Schuebel, K and Mudra, S and Meeks, BK and Tuason, RTS and Brooks, AT and Kazmi, N and Yang, S and Ratteree, K and Diazgranados, N and Krumlauf, M and Wallen, GR and Goldman, D}, title = {Longitudinal gut microbiome changes in alcohol use disorder are influenced by abstinence and drinking quantity.}, journal = {Gut microbes}, volume = {11}, number = {6}, pages = {1608-1631}, pmid = {32615913}, issn = {1949-0984}, support = {Z01 AA000280/ImNIH/Intramural NIH HHS/United States ; }, mesh = {Adult ; Alcohol Abstinence/psychology ; Alcohol Drinking/*metabolism/*psychology ; Ethanol/adverse effects/analysis/*metabolism ; Feces/microbiology ; Female ; Gastrointestinal Microbiome/*drug effects ; Humans ; Longitudinal Studies ; Male ; Microbiota/drug effects ; Middle Aged ; }, abstract = {Many patients with alcohol use disorder (AUD) consume alcohol chronically and in large amounts that alter intestinal microbiota, damage the gastrointestinal tract, and thereby injure other organs via malabsorption and intestinal inflammation. We hypothesized that alcohol consumption and subsequent abstinence would change the gut microbiome in adults admitted to a treatment program. Stool and oral specimens, diet data, gastrointestinal assessment scores, anxiety, depression measures and drinking amounts were collected longitudinally for up to 4 weeks in 22 newly abstinent inpatients with AUD who were dichotomized as less heavy drinkers (LHD, <10 drinks/d) and very heavy drinkers (VHD, 10 or more drinks/d). Next-generation 16 S rRNA gene sequencing was performed to measure the gut and oral microbiome at up to ten time points/subject and LHD and VHD were compared for change in principal components, Shannon diversity index and specific genera. The first three principal components explained 46.7% of the variance in gut microbiome diversity across time and all study subjects, indicating the change in gut microbiome following abstinence. The first time point was an outlier in three-dimensional principal component space versus all other time points. The gut microbiota in LHD and VHD were significantly dissimilar in change from day 1 to day 5 (p = .03) and from day 1 to week 3 (p = .02). The VHD drinking group displayed greater change from baseline. The Shannon diversity index of the gut microbiome changed significantly during abstinence in five participants. In both groups, the Shannon diversity was lower in the oral microbiome than gut. Ten total genera were shared between oral and stool in the AUD participants. These data were compared with healthy controls from the Human Microbiome Project to investigate the concept of a core microbiome. Rapid changes in gut microbiome following abstinence from alcohol suggest resilience of the gut microbiome in AUD and reflects the benefits of refraining from the highest levels of alcohol and potential benefits of abstinence.}, }
@article {pmid32612660, year = {2020}, author = {Ogunrinola, GA and Oyewale, JO and Oshamika, OO and Olasehinde, GI}, title = {The Human Microbiome and Its Impacts on Health.}, journal = {International journal of microbiology}, volume = {2020}, number = {}, pages = {8045646}, pmid = {32612660}, issn = {1687-918X}, abstract = {The human microbiome comprises bacteria, archaea, viruses, and eukaryotes which reside within and outside our bodies. These organisms impact human physiology, both in health and in disease, contributing to the enhancement or impairment of metabolic and immune functions. Micro-organisms colonise various sites on and in the human body, where they adapt to specific features of each niche. Facultative anaerobes are more dominant in the gastrointestinal tract, whereas strict aerobes inhabit the respiratory tract, nasal cavity, and skin surface. The indigenous organisms in the human body are well adapted to the immune system, due to the biological interaction of the organisms with the immune system over time. An alteration in the intestinal microbial community plays a major role in human health and disease pathogenesis. These alterations result from lifestyle and the presence of an underlying disease. Dysbiosis increases host susceptibility to infection, and the nature of which depends on the anatomical site involved. The unique diversity of the human microbiota accounts for the specific metabolic activities and functions of these micro-organisms within each body site. It is therefore important to understand the microbial composition and activities of the human microbiome as they contribute to health and disease.}, }
@article {pmid32607819, year = {2021}, author = {Ohadian Moghadam, S and Momeni, SA}, title = {Human microbiome and prostate cancer development: current insights into the prevention and treatment.}, journal = {Frontiers of medicine}, volume = {15}, number = {1}, pages = {11-32}, pmid = {32607819}, issn = {2095-0225}, mesh = {Bacteria ; Dysbiosis ; Humans ; Male ; *Microbiota ; *Prostatic Neoplasms/prevention &amp; control ; }, abstract = {The huge communities of microorganisms that symbiotically colonize humans are recognized as significant players in health and disease. The human microbiome may influence prostate cancer development. To date, several studies have focused on the effect of prostate infections as well as the composition of the human microbiome in relation to prostate cancer risk. Current studies suggest that the microbiota of men with prostate cancer significantly differs from that of healthy men, demonstrating that certain bacteria could be associated with cancer development as well as altered responses to treatment. In healthy individuals, the microbiome plays a crucial role in the maintenance of homeostasis of body metabolism. Dysbiosis may contribute to the emergence of health problems, including malignancy through affecting systemic immune responses and creating systemic inflammation, and changing serum hormone levels. In this review, we discuss recent data about how the microbes colonizing different parts of the human body including urinary tract, gastrointestinal tract, oral cavity, and skin might affect the risk of developing prostate cancer. Furthermore, we discuss strategies to target the microbiome for risk assessment, prevention, and treatment of prostate cancer.}, }
@article {pmid32605552, year = {2020}, author = {Rees, J and Christophersen, CC and Lewis, JR and Lo, J and Sambell, R and Costello, L and Walker, C and Byrne, MF and Boyce, MC and Newton, RU and Devine, A}, title = {The study protocol for a pseudo-randomised pre-post designed controlled intervention trial to study the effects of a 7-week cooking program on self-efficacy and biomarkers of health: the ECU lifestyle and biomarkers get connected study (ECULABJMOF) including the Jamie's Ministry of Food WA participant experience.}, journal = {BMC public health}, volume = {20}, number = {1}, pages = {1037}, pmid = {32605552}, issn = {1471-2458}, mesh = {Adult ; Australia ; Biomarkers ; Chronic Disease ; *Cooking ; Diet/adverse effects/statistics &amp; numerical data ; Female ; *Health Knowledge, Attitudes, Practice ; Health Promotion/*methods ; Humans ; Life Style ; Male ; Obesity/epidemiology/prevention &amp; control ; Personal Satisfaction ; Program Evaluation ; Research Design ; *Self Efficacy ; Surveys and Questionnaires ; Western Australia/epidemiology ; }, abstract = {BACKGROUND: Australia, like other nations, has experienced a shift in dietary patterns away from home cooking of nutritious foods, towards a reliance on pre-prepared convenience meals. These are typically energy-dense, nutrient-poor and contribute to the rising prevalence of obesity and chronic disease burden. The aims of this study were to evaluate whether a community-based cooking program instigated a change to participants' skills, attitudes, knowledge, enjoyment and satisfaction of cooking and cooking confidence (self-efficacy).<br><br>METHODS: The pseudo-random, pre-post study design consisted of an intervention and a control group. Participant recruitment and group allocation was based on their program start dates. Intervention participants were surveyed three times (baseline, 7&#x2009;weeks and 6&#x2009;months) and the control group were surveyed at baseline and 5&#x2009;weeks. All participants were registered via an online website and were 18&#x2009;years or over. Upon consent, participants were offered four levels of commitment, defined by different assessments. The minimum participation level included an online survey and levels 2, 3 and 4 involved attendance at a clinic with increasing functional, anthropometric and biomarker measurements. Primary endpoints were participants' cooking confidence as a proxy for self-efficacy. Secondary endpoints were dietary intake, physical activity levels, body composition, anthropometry, blood, urine and faecal biomarkers of systemic, physical and mental health.<br><br>DISCUSSION: The community cooking program provided participants with information and advice on food sourcing, preparation and nutrition to improve home cooking skills. The study was designed to explore whether food literacy programs are efficacious in improving participant physical health and well-being in order to combat the rise in obesity and diet-related disease. It will support future use of public health cooking program initiatives aimed at improving food literacy, self-efficacy and physical and mental health. The extensive data collected will inform future research into the relationship between diet, the gut-microbiota and human health.<br><br>TRIAL REGISTRATION: Retrospectively registered on 16.08.2019 with the Australian New Zealand Clinical Trials Registry (ANZCTR). ACTRN12619001144101 . Protocol version 4.}, }
@article {pmid32605102, year = {2020}, author = {Roder, T and Wüthrich, D and Bär, C and Sattari, Z and Ah, UV and Ronchi, F and Macpherson, AJ and Ganal-Vonarburg, SC and Bruggmann, R and Vergères, G}, title = {In Silico Comparison Shows that the Pan-Genome of a Dairy-Related Bacterial Culture Collection Covers Most Reactions Annotated to Human Microbiomes.}, journal = {Microorganisms}, volume = {8}, number = {7}, pages = {}, pmid = {32605102}, issn = {2076-2607}, support = {GRS-070/17//Gebert R&#xfc;f Stiftung/ ; }, abstract = {The diversity of the human microbiome is positively associated with human health. However, this diversity is endangered by Westernized dietary patterns that are characterized by a decreased nutrient variety. Diversity might potentially be improved by promoting dietary patterns rich in microbial strains. Various collections of bacterial cultures resulting from a century of dairy research are readily available worldwide, and could be exploited to contribute towards this end. We have conducted a functional in silico analysis of the metagenome of 24 strains, each representing one of the species in a bacterial culture collection composed of 626 sequenced strains, and compared the pathways potentially covered by this metagenome to the intestinal metagenome of four healthy, although overweight, humans. Remarkably, the pan-genome of the 24 strains covers 89% of the human gut microbiome's annotated enzymatic reactions. Furthermore, the dairy microbial collection covers biological pathways, such as methylglyoxal degradation, sulfate reduction, g-aminobutyric (GABA) acid degradation and salicylate degradation, which are differently covered among the four subjects and are involved in a range of cardiometabolic, intestinal, and neurological disorders. We conclude that microbial culture collections derived from dairy research have the genomic potential to complement and restore functional redundancy in human microbiomes.}, }
@article {pmid32604176, year = {2020}, author = {Qian, XB and Chen, T and Xu, YP and Chen, L and Sun, FX and Lu, MP and Liu, YX}, title = {A guide to human microbiome research: study design, sample collection, and bioinformatics analysis.}, journal = {Chinese medical journal}, volume = {133}, number = {15}, pages = {1844-1855}, pmid = {32604176}, issn = {2542-5641}, mesh = {*Computational Biology ; Humans ; *Microbiota/genetics ; Reproducibility of Results ; Research Design ; Specimen Handling ; }, abstract = {The purpose of this review is to provide medical researchers, especially those without a bioinformatics background, with an easy-to-understand summary of the concepts and technologies used in microbiome research. First, we define primary concepts such as microbiota, microbiome, and metagenome. Then, we discuss study design schemes, the methods of sample size calculation, and the methods for improving the reliability of research. We emphasize the importance of negative and positive controls in this section. Next, we discuss statistical analysis methods used in microbiome research, focusing on problems with multiple comparisons and ways to compare β-diversity between groups. Finally, we provide step-by-step pipelines for bioinformatics analysis. In summary, the meticulous study design is a key step to obtaining meaningful results, and appropriate statistical methods are important for accurate interpretation of microbiome data. The step-by-step pipelines provide researchers with insights into newly developed bioinformatics analysis methods.}, }
@article {pmid32602257, year = {2021}, author = {Delbeke, H and Younas, S and Casteels, I and Joossens, M}, title = {Current knowledge on the human eye microbiome: a systematic review of available amplicon and metagenomic sequencing data.}, journal = {Acta ophthalmologica}, volume = {99}, number = {1}, pages = {16-25}, doi = {10.1111/aos.14508}, pmid = {32602257}, issn = {1755-3768}, mesh = {Bacteria/*genetics ; DNA, Bacterial/*genetics ; Eye Infections, Bacterial/*genetics/microbiology ; Humans ; Metagenomics/*methods ; Microbiota/*genetics ; }, abstract = {Insights in the ocular surface microbiome are still at an early stage and many more questions remain unanswered compared with other human-associated microbial communities. The current knowledge on the human microbiome changed our viewpoint on bacteria and human health and significantly enhanced our understanding of human pathophysiology. Also in ocular medicine, microbiome research might impact treatment. Here, we summarize the current knowledge on ocular microbiome research with a particular focus on potential confounding factors and their effects on microbiome composition. Moreover, we present the ocular surface core microbiome based on current available data and defined it as genera present in almost half of the published control cohorts with a relative abundance of at least 1%.}, }
@article {pmid32600759, year = {2020}, author = {Simões da Silva, TM and Piazentin, ACM and Mendonça, CMN and Converti, A and Bogsan, CSB and Mora, D and de Souza Oliveira, RP}, title = {Buffalo milk increases viability and resistance of probiotic bacteria in dairy beverages under in vitro simulated gastrointestinal conditions.}, journal = {Journal of dairy science}, volume = {103}, number = {9}, pages = {7890-7897}, doi = {10.3168/jds.2019-18078}, pmid = {32600759}, issn = {1525-3198}, mesh = {Animals ; Beverages ; *Buffaloes ; Cattle ; Cultured Milk Products/microbiology ; Dairy Products/*microbiology ; Female ; Fermentation ; Food Storage ; Gastrointestinal Tract/*metabolism ; Humans ; Lactobacillus acidophilus/metabolism ; *Microbial Viability ; Microbiota ; *Milk/metabolism ; *Probiotics/analysis ; Streptococcus thermophilus/metabolism ; Whey Proteins/analysis ; }, abstract = {Probiotic dairy beverages prepared from buffalo and cow milks with different levels of whey (0, 25, and 50%) were evaluated for kinetic fermentation parameters, protein and fat contents, post-acidification profile, viability of Streptococcus thermophilus, Lactobacillus bulgaricus, and Lactobacillus acidophilus during 21 d of refrigerated storage, and resistance to in vitro gastrointestinal conditions. Progressive acidification that occurred during storage of all dairy products was reduced in the presence of whey. Lactic acid bacteria showed viable cell counts at the end of shelf life, with the highest values (7.33 to 8.83 log cfu/mL) detected in buffalo dairy products. Compared with fermented cow milk products, those made with buffalo milk showed better bacterial viability during in vitro simulated gastrointestinal digestion, which suggests a beneficial protective effect on human microbiome.}, }
@article {pmid32599802, year = {2020}, author = {Marzano, V and Pane, S and Foglietta, G and Levi Mortera, S and Vernocchi, P and Onetti Muda, A and Putignani, L}, title = {Mass Spectrometry Based-Proteomic Analysis of Anisakis spp.: A Preliminary Study towards a New Diagnostic Tool.}, journal = {Genes}, volume = {11}, number = {6}, pages = {}, pmid = {32599802}, issn = {2073-4425}, mesh = {Animals ; Anisakiasis/diagnosis/*genetics/parasitology ; Anisakis/*genetics/pathogenicity ; Fishes/genetics/parasitology ; Larva/pathogenicity ; Proteome/*genetics ; *Proteomics ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization ; }, abstract = {Anisakiasis is nowadays a well-known infection, mainly caused by the accidental ingestion of Anisakis larvae, following the consumption of raw or undercooked fishes and cephalopods. Due to the similarity of symptoms with those of common gastrointestinal disorders, this infection is often underestimated, and the need for new specific diagnostic tools is becoming crucial. Given the remarkable impact that MALDI-TOF MS biotyping had in the last decade in clinical routine practice for the recognition of bacterial and fungi strains, a similar scenario could be foreseen for the identification of parasites, such as nematodes. In this work, a MALDI-TOF MS profiling of Anisakis proteome was pursued with a view to constructing a first spectral library for the diagnosis of Anisakis infections. At the same time, a shotgun proteomics approach by LC-ESI-MS/MS was performed on the two main fractions obtained from protein extraction, to evaluate the protein species enriched by the protocol. A set of MALDI-TOF MS signals associated with proteins originating in the ribosomal fraction of the nematode extract was selected as a potential diagnostic tool for the identification of Anisakis spp.}, }
@article {pmid32592144, year = {2020}, author = {Ouabbou, S and He, Y and Butler, K and Tsuang, M}, title = {Inflammation in Mental Disorders: Is the Microbiota the Missing Link?.}, journal = {Neuroscience bulletin}, volume = {36}, number = {9}, pages = {1071-1084}, pmid = {32592144}, issn = {1995-8218}, mesh = {Brain/*physiopathology ; *Gastrointestinal Microbiome ; Humans ; Inflammation/*physiopathology ; *Mental Disorders ; Mood Disorders ; Psychotic Disorders ; }, abstract = {Research suggests that inflammation is important in the pathophysiology of mental disorders. In addition, a growing body of evidence has led to the concept of the microbiota-gut-brain axis. To understand the potential interactions, we begin by exploring the liaison between the immune system and mental disorders, then we describe the evidence that the microbiota impact the immune response in the developing brain. Next, we review the literature that has documented microbiome alterations in major mental disorders. We end with a summary of therapeutic applications, ranging from psycho-biotics to immunomodulatory drugs that could affect the microbiota-gut-brain axis, and potential treatments to alleviate the adverse effects of antipsychotics. We conclude that there is promising evidence to support the position that the microbiota plays an important role in the immunological pathophysiology of mental disorders with an emphasis on psychotic disorders and mood disorders. However, more research is needed to elucidate the mechanisms.}, }
@article {pmid32587451, year = {2020}, author = {Xue, AJ and Miao, SJ and Sun, H and Qiu, XX and Wang, SN and Wang, L and Ye, ZQ and Zheng, CF and Huang, ZH and Wang, YH and Huang, Y}, title = {Intestinal dysbiosis in pediatric Crohn's disease patients with IL10RA mutations.}, journal = {World journal of gastroenterology}, volume = {26}, number = {22}, pages = {3098-3109}, pmid = {32587451}, issn = {2219-2840}, mesh = {Child ; *Crohn Disease/diagnosis/genetics ; *Dysbiosis ; Feces ; Humans ; *Interleukin-10 Receptor alpha Subunit ; Mutation ; RNA, Ribosomal, 16S ; }, abstract = {BACKGROUND: Several studies have employed animal models to explore the association between microbiota and interleukin (IL) 10 signaling; however, limited information is available about the human microbiome.<br><br>AIM: To characterize the microbiome in patients with IL10RA mutations and to explore the association between gut dysbiosis and disease severity.<br><br>METHODS: Fecal samples were collected from patients who were diagnosed with loss-of-function mutations in the IL10RA gene between January 2017 and July 2018 at the Children's Hospital of Fudan University. Age-matched volunteer children were recruited as healthy controls. Patients with Crohn's disease (CD) were used as disease controls to standardize the antibiotic exposure. Microbial DNA was extracted from the fecal samples. All analyses were based on the 16S rRNA gene sequencing data.<br><br>RESULTS: Seventeen patients with IL10RA mutations (IL10RA group), 17 patients with pediatric CD, and 26 healthy children were included. Both patients with IL10RA mutations and those with CD exhibited a reduced diversity of gut microbiome with increased variability. The relative abundance of Firmicutes was substantially increased in the IL10RA group (P = 0.02). On further comparison of the relative abundance of taxa between patients with IL10RA mutations and healthy children, 13 taxa showed significant differences. The IL10RA-specific dysbiosis indices exhibited a significant positive correlation with weighted pediatric CD activity index and simple endoscopic score for CD.<br><br>CONCLUSION: In patients with IL10RA mutations and early onset inflammatory bowel disease, gut dysbiosis shows a moderate association with disease severity.}, }
@article {pmid32584047, year = {2021}, author = {Tavakoli, S and Kari, OK and Turunen, T and Lajunen, T and Schmitt, M and Lehtinen, J and Tasaka, F and Parkkila, P and Ndika, J and Viitala, T and Alenius, H and Urtti, A and Subrizi, A}, title = {Diffusion and Protein Corona Formation of Lipid-Based Nanoparticles in the Vitreous Humor: Profiling and Pharmacokinetic Considerations.}, journal = {Molecular pharmaceutics}, volume = {18}, number = {2}, pages = {699-713}, pmid = {32584047}, issn = {1543-8392}, mesh = {Adsorption ; Animals ; Diffusion ; Drug Compounding/methods ; Humans ; Intravitreal Injections ; Liposomes ; Nanoparticles/*chemistry ; Ophthalmic Solutions/*administration &amp; dosage/pharmacokinetics ; Particle Size ; Polyethylene Glycols/chemistry ; Protein Corona/analysis/metabolism ; Proteomics ; Retinal Diseases/*drug therapy ; Surface Properties ; Sus scrofa ; Vitreous Body/*metabolism ; }, abstract = {The vitreous humor is the first barrier encountered by intravitreally injected nanoparticles. Lipid-based nanoparticles in the vitreous are studied by evaluating their diffusion with single-particle tracking technology and by characterizing their protein coronae with surface plasmon resonance and high-resolution proteomics. Single-particle tracking results indicate that the vitreal mobility of the formulations is dependent on their charge. Anionic and neutral formulations are mobile, whereas larger (>200 nm) neutral particles have restricted diffusion, and cationic particles are immobilized in the vitreous. PEGylation increases the mobility of cationic and larger neutral formulations but does not affect anionic and smaller neutral particles. Convection has a significant role in the pharmacokinetics of nanoparticles, whereas diffusion drives the transport of antibodies. Surface plasmon resonance studies determine that the vitreal corona of anionic formulations is sparse. Proteomics data reveals 76 differentially abundant proteins, whose enrichment is specific to either the hard or the soft corona. PEGylation does not affect protein enrichment. This suggests that protein-specific rather than formulation-specific factors are drivers of protein adsorption on nanoparticles in the vitreous. In summary, our findings contribute to understanding the pharmacokinetics of nanoparticles in the vitreous and help advance the development of nanoparticle-based treatments for eye diseases.}, }
@article {pmid32582274, year = {2020}, author = {Jiang, S and Xiao, G and Koh, AY and Chen, Y and Yao, B and Li, Q and Zhan, X}, title = {HARMONIES: A Hybrid Approach for Microbiome Networks Inference via Exploiting Sparsity.}, journal = {Frontiers in genetics}, volume = {11}, number = {}, pages = {445}, pmid = {32582274}, issn = {1664-8021}, support = {P30 CA142543/CA/NCI NIH HHS/United States ; R01 GM126479/GM/NIGMS NIH HHS/United States ; R01 HG008983/HG/NHGRI NIH HHS/United States ; }, abstract = {The human microbiome is a collection of microorganisms. They form complex communities and collectively affect host health. Recently, the advances in next-generation sequencing technology enable the high-throughput profiling of the human microbiome. This calls for a statistical model to construct microbial networks from the microbiome sequencing count data. As microbiome count data are high-dimensional and suffer from uneven sampling depth, over-dispersion, and zero-inflation, these characteristics can bias the network estimation and require specialized analytical tools. Here we propose a general framework, HARMONIES, Hybrid Approach foR MicrobiOme Network Inferences via Exploiting Sparsity, to infer a sparse microbiome network. HARMONIES first utilizes a zero-inflated negative binomial (ZINB) distribution to model the skewness and excess zeros in the microbiome data, as well as incorporates a stochastic process prior for sample-wise normalization. This approach infers a sparse and stable network by imposing non-trivial regularizations based on the Gaussian graphical model. In comprehensive simulation studies, HARMONIES outperformed four other commonly used methods. When using published microbiome data from a colorectal cancer study, it discovered a novel community with disease-enriched bacteria. In summary, HARMONIES is a novel and useful statistical framework for microbiome network inference, and it is available at https://github.com/shuangj00/HARMONIES.}, }
@article {pmid32581284, year = {2020}, author = {Hermes, GDA and Eckermann, HA and de Vos, WM and de Weerth, C}, title = {Does entry to center-based childcare affect gut microbial colonization in young infants?.}, journal = {Scientific reports}, volume = {10}, number = {1}, pages = {10235}, pmid = {32581284}, issn = {2045-2322}, mesh = {Bacteria/*classification/genetics/isolation &amp; purification ; Bayes Theorem ; Case-Control Studies ; Child Day Care Centers ; Feces/*microbiology ; Female ; Gastrointestinal Microbiome ; Humans ; Infant ; Infant Care/*methods ; Longitudinal Studies ; Male ; Netherlands ; Phylogeny ; Sequence Analysis, DNA/*methods ; }, abstract = {Entry to center-based childcare (CC) at three months of life can be an important challenge for infants as it includes major stressors such as long maternal separations and frequently changing caregivers. Stress and the new environment may in turn alter the composition of the gut microbiota with possible implications for future health outcomes. As part of an ongoing longitudinal study, we investigated whether CC, as compared to being cared for by the parents at home, alters the composition of the gut microbiota, while accounting for known covariates of the infant gut microbiota. Stool samples of infants who entered CC (n = 49) and control infants (n = 49) were obtained before and four weeks after CC entrance. Using Redundancy analysis, Random Forests and Bayesian linear models we found that infant gut microbiota was not affected in a uniform way by entry to CC. In line with the literature, breastfeeding, birth mode, age, and the presence of siblings were shown to significantly impact the microbial composition.}, }
@article {pmid32578402, year = {2020}, author = {López-Laguna, H and Sánchez-García, L and Serna, N and Voltà-Durán, E and Sánchez, JM and Sánchez-Chardi, A and Unzueta, U and Łoś, M and Villaverde, A and Vázquez, E}, title = {Engineering Protein Nanoparticles Out from Components of the Human Microbiome.}, journal = {Small (Weinheim an der Bergstrasse, Germany)}, volume = {16}, number = {30}, pages = {e2001885}, doi = {10.1002/smll.202001885}, pmid = {32578402}, issn = {1613-6829}, mesh = {Drug Delivery Systems ; Humans ; *Microbiota ; *Nanoparticles ; Peptides ; Protein Engineering ; }, abstract = {Nanoscale protein materials are highly convenient as vehicles for targeted drug delivery because of their structural and functional versatility. Selective binding to specific cell surface receptors and penetration into target cells require the use of targeting peptides. Such homing stretches should be incorporated to larger proteins that do not interact with body components, to prevent undesired drug release into nontarget organs. Because of their low interactivity with human body components and their tolerated immunogenicity, proteins derived from the human microbiome are appealing and fully biocompatible building blocks for the biofabrication of nonreactive, inert protein materials within the nanoscale. Several phage and phage-like bacterial proteins with natural structural roles are produced in Escherichia coli as polyhistidine-tagged recombinant proteins, looking for their organization as discrete, nanoscale particulate materials. While all of them self-assemble in a variety of sizes, the stability of the resulting constructs at 37 °C is found to be severely compromised. However, the fine adjustment of temperature and Zn[2+] concentration allows the formation of robust nanomaterials, fully stable in complex media and under physiological conditions. Then, microbiome-derived proteins show promise for the regulatable construction of scaffold protein nanomaterials, which can be tailored and strengthened by simple physicochemical approaches.}, }
@article {pmid32574814, year = {2021}, author = {Chauhan, V and Kanwar, SS}, title = {Lipopeptide(s) associated with human microbiome as potent cancer drug.}, journal = {Seminars in cancer biology}, volume = {70}, number = {}, pages = {128-133}, doi = {10.1016/j.semcancer.2020.06.012}, pmid = {32574814}, issn = {1096-3650}, mesh = {Animals ; Antineoplastic Agents/*administration &amp; dosage ; *Gastrointestinal Microbiome ; Humans ; Lipopeptides/*administration &amp; dosage ; Neoplasms/*drug therapy/microbiology ; }, abstract = {Human microbiota comprises of trillions of microbes which have evolved with and continued to live on/ within their human hosts. Different environmental factors and diet have a large impact upon human microbiota population. These microorganisms live in synergy with their hosts and are beneficial to the host in many different ways. Many microorganisms help to fight against human diseases. Cancer is one such diseases which effects a large human population often leading to death. Cancer is also one of the most fatal human diseases killing millions of people world-wide every year. Though many treatment procedures are available but none is 100 % effective in curing cancer. In this review, we seek to understand the role of human microbiota in cancer treatment. Lipopeptide(s) (LPs) produced by different microorganisms can act as efficient drug(s) against cancer. LPs are low molecular weight lipo-proteins that are also known for their anti-cancer activities. As human microbiota belongs to an environment within the host body, a drug prepared using these microorganisms will be easily accepted by the body. This novel approach of using LPs produced by human microbiota can be considered for the much needed change in cancer treatment. Therefore, it is proposed that research should focus on the host-microbe interaction which could pave the way in understanding role played by these microorganisms in cancer treatment.}, }
@article {pmid32574290, year = {2020}, author = {Baud, D and Dimopoulou Agri, V and Gibson, GR and Reid, G and Giannoni, E}, title = {Using Probiotics to Flatten the Curve of Coronavirus Disease COVID-2019 Pandemic.}, journal = {Frontiers in public health}, volume = {8}, number = {}, pages = {186}, pmid = {32574290}, issn = {2296-2565}, mesh = {*COVID-19/prevention &amp; control/therapy ; Diarrhea/prevention &amp; control ; Gastrointestinal Microbiome ; Humans ; *Infection Control ; Probiotics/*administration &amp; dosage ; Respiratory Tract Infections/prevention &amp; control ; SARS-CoV-2 ; }, }
@article {pmid32571986, year = {2020}, author = {Alverdy, JC and Keskey, R and Thewissen, R}, title = {Can the Cecal Ligation and Puncture Model Be Repurposed To Better Inform Therapy in Human Sepsis?.}, journal = {Infection and immunity}, volume = {88}, number = {9}, pages = {}, pmid = {32571986}, issn = {1098-5522}, support = {R01 GM062344/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Anti-Bacterial Agents/*pharmacology ; Bacterial Typing Techniques ; Cecum/microbiology/surgery ; Cytokines/biosynthesis/immunology ; *Disease Models, Animal ; *Food, Formulated ; Gastrointestinal Microbiome/*immunology ; Humans ; Intraabdominal Infections/immunology/microbiology/mortality/*therapy ; Ligation/methods ; Mice ; Punctures/methods ; Sepsis/immunology/microbiology/mortality/*therapy ; Survival Analysis ; }, abstract = {A recent report by the National Institutes of Health on sepsis research has implied there is a trend to move away from mouse models of sepsis. The most commonly used animal model to study the pathogenesis of human sepsis is cecal ligation and puncture (CLP) in mice. The model has been the mainstay of sepsis research for decades and continues to be considered the gold standard to inform novel pathways of sepsis physiology and its therapeutic direction. As there have been many criticisms of the model, particularly regarding its relevance to human disease, how this model might be repurposed to be more reflective of the human condition begs discussion. In this piece, we compare and contrast the mouse microbiome of the CLP model to the emerging science of the microbiome of human sepsis and discuss the relevance for mice to harbor the specific pathogens present in the human microbiome during sepsis, as well as an underlying disease process to mimic the characteristics of those patients with undesirable outcomes. How to repurpose this model to incorporate these "human factors" is discussed in detail and suggestions offered.}, }
@article {pmid32564483, year = {2020}, author = {Rattan, P and Minacapelli, CD and Rustgi, V}, title = {The Microbiome and Hepatocellular Carcinoma.}, journal = {Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society}, volume = {26}, number = {10}, pages = {1316-1327}, doi = {10.1002/lt.25828}, pmid = {32564483}, issn = {1527-6473}, mesh = {Animals ; *Carcinoma, Hepatocellular ; *Gastrointestinal Microbiome ; Humans ; *Liver Neoplasms ; *Liver Transplantation ; *Microbiota ; }, abstract = {The human microbiome is a vast and complex system encompassing all of the microbes and their genes that occupy the environmentally exposed surfaces of the human body. The gut microbiota and its associated microbiome play an integral role in mammalian metabolism and immune tolerance as well as in immunocompetence. Disruptions in the human gut microbiome are associated with a cycle of hepatocyte injury and regeneration characteristic of chronic liver disease. The persistence of this inflammation has been shown to induce the accumulation of genetic and epigenetic changes leading to hepatocellular carcinoma (HCC). Therefore, the importance and prognostic influence of the gut microbiome on hepatocarcinogenesis has been increasingly studied in recent years. This review discusses the mechanisms by which imbalances in the gut microbiome disturb the gut-liver axis to impact hepatocarcinogenesis, including disruption of the intestinal barrier, changes in bile acid metabolism, and reduction in tumor-suppressing microRNA. Furthermore, this review summarizes recent advances in potential microbiome-based therapeutic opportunities in HCC.}, }
@article {pmid32563152, year = {2020}, author = {Hu, Y and Fang, L and Nicholson, C and Wang, K}, title = {Implications of Error-Prone Long-Read Whole-Genome Shotgun Sequencing on Characterizing Reference Microbiomes.}, journal = {iScience}, volume = {23}, number = {6}, pages = {101223}, pmid = {32563152}, issn = {2589-0042}, support = {R01 GM132713/GM/NIGMS NIH HHS/United States ; }, abstract = {Long-read sequencing techniques, such as the Oxford Nanopore Technology, can generate reads that are tens of kilobases in length and are therefore particularly relevant for microbiome studies. However, owing to the higher per-base error rates than typical short-read sequencing, the application of long-read sequencing on microbiomes remains largely unexplored. Here we deeply sequenced two human microbiota mock community samples (HM-276D and HM-277D) from the Human Microbiome Project. We showed that assembly programs consistently achieved high accuracy (∼99%) and completeness (∼99%) for bacterial strains with adequate coverage. We also found that long-read sequencing provides accurate estimates of species-level abundance (R = 0.94 for 20 bacteria with abundance ranging from 0.005% to 64%). Our results not only demonstrate the feasibility of characterizing complete microbial genomes and populations from error-prone Nanopore sequencing data but also highlight necessary bioinformatics improvements for future metagenomics tool development.}, }
@article {pmid32559728, year = {2020}, author = {Ma, ZS}, title = {Critical Network Structures and Medical Ecology Mechanisms Underlying Human Microbiome-Associated Diseases.}, journal = {iScience}, volume = {23}, number = {6}, pages = {101195}, pmid = {32559728}, issn = {2589-0042}, abstract = {A fundamental problem in studies on human microbiome-associated diseases (MADs) is to understand the relationships between microbiome structures and health status of hosts. For example, species diversity metrics have been routinely evaluated in virtually all studies on MADs, yet a recent meta-analysis revealed that, in only approximately one-third of the cases, diversity and diseases were related. In this study, we ask whether Hubbell's neutral theory (supplemented with the normalized stochasticity ratio [NSR]) or critical microbiome network structures may offer better alternatives. Whereas neutral theory and NSR focus on stochastic processes, we use core/periphery and high-salience skeleton networks to evaluate deterministic, asymmetrical niche effects, assuming that all species or their interactions were not "born" equal and focusing on non-neutral, critical network structures. We found that properties of critical network structures are more indicative of disease effects. Finally, seven findings (mechanisms, interpretations, and postulations) regarding medical ecology mechanisms underlying MADs were summarized.}, }
@article {pmid32559614, year = {2020}, author = {Hampton-Marcell, JT and Larsen, P and Anton, T and Cralle, L and Sangwan, N and Lax, S and Gottel, N and Salas-Garcia, M and Young, C and Duncan, G and Lopez, JV and Gilbert, JA}, title = {Detecting personal microbiota signatures at artificial crime scenes.}, journal = {Forensic science international}, volume = {313}, number = {}, pages = {110351}, doi = {10.1016/j.forsciint.2020.110351}, pmid = {32559614}, issn = {1872-6283}, mesh = {*Crime ; Forensic Sciences/methods ; Humans ; *Microbiota/genetics ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; Skin/*microbiology ; Statistics as Topic ; *Touch ; }, abstract = {When mapped to the environments we interact with on a daily basis, the 36 million microbial cells per hour that humans emit leave a trail of evidence that can be leveraged for forensic analysis. We employed 16S rRNA amplicon sequencing to map unique microbial sequence variants between human skin and building surfaces in three experimental conditions: over time during controlled and uncontrolled incidental interactions with a door handle, and during multiple mock burglaries in ten real residences. We demonstrate that humans (n = 30) leave behind microbial signatures that can be used to track interaction with various surfaces within a building, but the likelihood of accurately detecting the specific burglar for a given home was between 20-25%. Also, the human microbiome contains rare microbial taxa that can be combined to create a unique microbial profile, which when compared to 600 other individuals can improve our ability to link an individual 'burglar' to a residence. In total, 5512 discriminating, non-singleton unique exact sequence variants (uESVs) were identified as unique to an individual, with a minimum of 1 and a maximum of 568, suggesting some people maintain a greater degree of unique taxa compared to our population of 600. Approximate 60-77% of the unique exact sequence variants originated from the hands of participants, and these microbial discriminators spanned 36 phyla but were dominated by the Proteobacteria (34%). A fitted regression generated to determine whether an intruder's uESVs found on door handles in an office decayed over time in the presence or absence of office workers, found no significant shift in proportion of uESVs over time irrespective of the presence of office workers. While it was possible to detect the correct burglars' microbiota as having contributed to the invaded space, the predictions were very weak in comparison to accepted forensic standards. This suggests that at this time 16S rRNA amplicon sequencing of the built environment microbiota cannot be used as a reliable trace evidence standard for criminal investigations.}, }
@article {pmid32556166, year = {2020}, author = {De Filippis, F and Pasolli, E and Ercolini, D}, title = {The food-gut axis: lactic acid bacteria and their link to food, the gut microbiome and human health.}, journal = {FEMS microbiology reviews}, volume = {44}, number = {4}, pages = {454-489}, pmid = {32556166}, issn = {1574-6976}, mesh = {*Food Microbiology ; *Gastrointestinal Microbiome ; *Health ; Humans ; Lactobacillales/*physiology ; }, abstract = {Lactic acid bacteria (LAB) are present in foods, the environment and the animal gut, although fermented foods (FFs) are recognized as the primary niche of LAB activity. Several LAB strains have been studied for their health-promoting properties and are employed as probiotics. FFs are recognized for their potential beneficial effects, which we review in this article. They are also an important source of LAB, which are ingested daily upon FF consumption. In this review, we describe the diversity of LAB and their occurrence in food as well as the gut microbiome. We discuss the opportunities to study LAB diversity and functional properties by considering the availability of both genomic and metagenomic data in public repositories, as well as the different latest computational tools for data analysis. In addition, we discuss the role of LAB as potential probiotics by reporting the prevalence of key genomic features in public genomes and by surveying the outcomes of LAB use in clinical trials involving human subjects. Finally, we highlight the need for further studies aimed at improving our knowledge of the link between LAB-fermented foods and the human gut from the perspective of health promotion.}, }
@article {pmid32551196, year = {2020}, author = {Coil, DA and Neches, RY and Lang, JM and Jospin, G and Brown, WE and Cavalier, D and Hampton-Marcell, J and Gilbert, JA and Eisen, JA}, title = {Bacterial communities associated with cell phones and shoes.}, journal = {PeerJ}, volume = {8}, number = {}, pages = {e9235}, pmid = {32551196}, issn = {2167-8359}, abstract = {BACKGROUND: Every human being carries with them a collection of microbes, a collection that is likely both unique to that person, but also dynamic as a result of significant flux with the surrounding environment. The interaction of the human microbiome (i.e., the microbes that are found directly in contact with a person in places such as the gut, mouth, and skin) and the microbiome of accessory objects (e.g., shoes, clothing, phones, jewelry) is of potential interest to both epidemiology and the developing field of microbial forensics. Therefore, the microbiome of personal accessories are of interest because they serve as both a microbial source and sink for an individual, they may provide information about the microbial exposure experienced by an individual, and they can be sampled non-invasively.<br><br>FINDINGS: We report here a large-scale study of the microbiome found on cell phones and shoes. Cell phones serve as a potential source and sink for skin and oral microbiome, while shoes can act as sampling devices for microbial environmental experience. Using 16S rRNA gene sequencing, we characterized the microbiome of thousands of paired sets of cell phones and shoes from individuals at sporting events, museums, and other venues around the United States.<br><br>CONCLUSIONS: We place this data in the context of previous studies and demonstrate that the microbiome of phones and shoes are different. This difference is driven largely by the presence of "environmental" taxa (taxa from groups that tend to be found in places like soil) on shoes and human-associated taxa (taxa from groups that are abundant in the human microbiome) on phones. This large dataset also contains many novel taxa, highlighting the fact that much of microbial diversity remains uncharacterized, even on commonplace objects.}, }
@article {pmid32546787, year = {2020}, author = {Puebla-Barragan, S and Renaud, J and Sumarah, M and Reid, G}, title = {Malodorous biogenic amines in Escherichia coli-caused urinary tract infections in women-a metabolomics approach.}, journal = {Scientific reports}, volume = {10}, number = {1}, pages = {9703}, pmid = {32546787}, issn = {2045-2322}, mesh = {Biogenic Amines/*metabolism ; Cadaverine/metabolism ; Escherichia coli Infections/metabolism/*microbiology ; Metabolomics ; Methylamines/metabolism ; Odorants ; Putrescine/metabolism ; Tyramine/metabolism ; Urinary Tract Infections/*microbiology ; Uropathogenic Escherichia coli/*metabolism ; }, abstract = {Many women suffer from urinary tract infections (UTIs). In addition to pain and increased urgency to urinate, malodour is a significant issue for these patients. The specific factors causing this malodour are unclear, and there are no targeted treatment options to counteract it effectively. We used a metabolomics approach to compare the chemical composition of metabolites in the urine of women with E. coli UTIs (n = 15) and those who are healthy (n = 10). The biogenic amines trimethylamine and putrescine, which cause malodour in other urogenital conditions, were significantly increased in UTI patients. Conversely, the precursor of trimethylamine, trimethylamine N-oxide, was lower. To further confirm the source of the malodorous compounds, in vitro experiments were conducted by incubating strains of uropathogenic E. coli in sterilized urine from healthy women. All tested strains accumulated trimethylamine and putrescine. Notably, cadaverine was also produced by E. coli strains in vitro; however, it was not significantly different between both groups. We confirmed that the malodorous amines TMA and putrescine are found in higher concentrations in the urine of patients with an E.coli-caused UTI.}, }
@article {pmid32544460, year = {2020}, author = {Kenny, DJ and Plichta, DR and Shungin, D and Koppel, N and Hall, AB and Fu, B and Vasan, RS and Shaw, SY and Vlamakis, H and Balskus, EP and Xavier, RJ}, title = {Cholesterol Metabolism by Uncultured Human Gut Bacteria Influences Host Cholesterol Level.}, journal = {Cell host &amp; microbe}, volume = {28}, number = {2}, pages = {245-257.e6}, pmid = {32544460}, issn = {1934-6069}, support = {R01 HL131015/HL/NHLBI NIH HHS/United States ; R01 HL092577/HL/NHLBI NIH HHS/United States ; P30 DK034854/DK/NIDDK NIH HHS/United States ; HHSN268201500001I/HL/NHLBI NIH HHS/United States ; T32 GM095450/GM/NIGMS NIH HHS/United States ; N01HC25195/HL/NHLBI NIH HHS/United States ; F32 MH095450/MH/NIMH NIH HHS/United States ; 75N92019D00031/HL/NHLBI NIH HHS/United States ; HHSN268201500001C/HL/NHLBI NIH HHS/United States ; P30 DK043351/DK/NIDDK NIH HHS/United States ; }, mesh = {Bacteria/enzymology/genetics/*metabolism ; Cholestanol/*biosynthesis ; Cholesterol/*blood/*metabolism ; Feces/chemistry/microbiology ; Gastrointestinal Microbiome/genetics/*physiology ; Humans ; Lipid Metabolism/physiology ; Metabolomics ; Metagenomics ; Oxidoreductases/genetics/*metabolism ; }, abstract = {The human microbiome encodes extensive metabolic capabilities, but our understanding of the mechanisms linking gut microbes to human metabolism remains limited. Here, we focus on the conversion of cholesterol to the poorly absorbed sterol coprostanol by the gut microbiota to develop a framework for the identification of functional enzymes and microbes. By integrating paired metagenomics and metabolomics data from existing cohorts with biochemical knowledge and experimentation, we predict and validate a group of microbial cholesterol dehydrogenases that contribute to coprostanol formation. These enzymes are encoded by ismA genes in a clade of uncultured microorganisms, which are prevalent in geographically diverse human cohorts. Individuals harboring coprostanol-forming microbes have significantly lower fecal cholesterol levels and lower serum total cholesterol with effects comparable to those attributed to variations in lipid homeostasis genes. Thus, cholesterol metabolism by these microbes may play important roles in reducing intestinal and serum cholesterol concentrations, directly impacting human health.}, }
@article {pmid32541790, year = {2020}, author = {Diakite, A and Dubourg, G and Dione, N and Afouda, P and Bellali, S and Ngom, II and Valles, C and Tall, ML and Lagier, JC and Raoult, D}, title = {Optimization and standardization of the culturomics technique for human microbiome exploration.}, journal = {Scientific reports}, volume = {10}, number = {1}, pages = {9674}, pmid = {32541790}, issn = {2045-2322}, mesh = {Bacteria/*classification/*growth &amp; development/isolation &amp; purification ; Bacteriological Techniques/methods/*standards ; Culture Media/chemistry ; Feces/*microbiology ; Humans ; Microbiota ; Phylogeny ; RNA, Bacterial/genetics ; RNA, Ribosomal, 16S/genetics ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization ; Workflow ; }, abstract = {Culturomics is a high-throughput culture approach that has dramatically contributed to the recent renewal of culture. While metagenomics enabled substantial advances in exploring the microbiota, culturomics significantly expanded our knowledge regarding the bacterial gut repertoire through the discovery and the description of hundreds of new taxa. While this approach relies on the variation of culture conditions and media, we have tested so far more than 300 conditions since the beginning of culturomics studies. In this context, we aimed herein to identify the most profitable conditions for optimizing culturomics approach. For this purpose, we have analysed a set of 58 culturomics conditions that were previously applied to 8 faecal specimens, enabling the isolation of 497 bacterial species. As a result, we were able to reduce the number of conditions used to isolate these 497 of more than a half (i.e. to 25 culture conditions). We have also established a list of the 16 conditions that allowed to capture 98% of the total number of species previously isolated. These data constitute a methodological starting point for culture-based microbiota studies by improving the culturomics workflow without any loss of captured bacterial diversity.}, }
@article {pmid32539695, year = {2020}, author = {Philips, A and Stolarek, I and Handschuh, L and Nowis, K and Juras, A and Trzciński, D and Nowaczewska, W and Wrzesińska, A and Potempa, J and Figlerowicz, M}, title = {Analysis of oral microbiome from fossil human remains revealed the significant differences in virulence factors of modern and ancient Tannerella forsythia.}, journal = {BMC genomics}, volume = {21}, number = {1}, pages = {402}, pmid = {32539695}, issn = {1471-2164}, support = {R21 DE026280/DE/NIDCR NIH HHS/United States ; R21DE026280/DE/NIDCR NIH HHS/United States ; }, mesh = {Body Remains/*microbiology ; Fossils/*microbiology ; *Gastrointestinal Microbiome ; Genome, Bacterial ; Genomics ; Humans ; Metagenome ; Mouth/*microbiology ; Periodontitis/microbiology ; Periodontium/microbiology ; Tannerella forsythia/*genetics/*pathogenicity ; Tooth/microbiology ; Virulence Factors/*genetics ; }, abstract = {BACKGROUND: Recent advances in the next-generation sequencing (NGS) allowed the metagenomic analyses of DNA from many different environments and sources, including thousands of years old skeletal remains. It has been shown that most of the DNA extracted from ancient samples is microbial. There are several reports demonstrating that the considerable fraction of extracted DNA belonged to the bacteria accompanying the studied individuals before their death.<br><br>RESULTS: In this study we scanned 344 microbiomes from 1000- and 2000- year-old human teeth. The datasets originated from our previous studies on human ancient DNA (aDNA) and on microbial DNA accompanying human remains. We previously noticed that in many samples infection-related species have been identified, among them Tannerella forsythia, one of the most prevalent oral human pathogens. Samples containing sufficient amount of T. forsythia aDNA for a complete genome assembly were selected for thorough analyses. We confirmed that the T. forsythia-containing samples have higher amounts of the periodontitis-associated species than the control samples. Despites, other pathogens-derived aDNA was found in the tested samples it was too fragmented and damaged to allow any reasonable reconstruction of these bacteria genomes. The anthropological examination of ancient skulls from which the T. forsythia-containing samples were obtained revealed the pathogenic alveolar bone loss in tooth areas characteristic for advanced periodontitis. Finally, we analyzed the genetic material of ancient T. forsythia strains. As a result, we assembled four ancient T. forsythia genomes - one 2000- and three 1000- year-old. Their comparison with contemporary T. forsythia genomes revealed a lower genetic diversity within the four ancient strains than within contemporary strains. We also investigated the genes of T. forsythia virulence factors and found that several of them (KLIKK protease and bspA genes) differ significantly between ancient and modern bacteria.<br><br>CONCLUSIONS: In summary, we showed that NGS screening of the ancient human microbiome is a valid approach for the identification of disease-associated microbes. Following this protocol, we provided a new set of information on the emergence, evolution and virulence factors of T. forsythia, the member of the oral dysbiotic microbiome.}, }
@article {pmid32536582, year = {2021}, author = {Jian, C and Luukkonen, P and Sädevirta, S and Yki-Järvinen, H and Salonen, A}, title = {Impact of short-term overfeeding of saturated or unsaturated fat or sugars on the gut microbiota in relation to liver fat in obese and overweight adults.}, journal = {Clinical nutrition (Edinburgh, Scotland)}, volume = {40}, number = {1}, pages = {207-216}, doi = {10.1016/j.clnu.2020.05.008}, pmid = {32536582}, issn = {1532-1983}, mesh = {Body Mass Index ; Diet, High-Fat/*adverse effects ; Dietary Sugars/administration &amp; dosage ; Eating/physiology ; Fasting/blood ; Fats, Unsaturated/administration &amp; dosage ; Fatty Acids/administration &amp; dosage ; Feces/microbiology ; Female ; Gastrointestinal Microbiome/*physiology ; Humans ; Liver/metabolism ; Male ; Middle Aged ; Non-alcoholic Fatty Liver Disease/*etiology ; Obesity/complications/*metabolism ; Overweight/complications/*metabolism ; }, abstract = {BACKGROUNDS &amp; AIMS: Intestinal microbiota may be causally involved in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). We aimed to study the effect of short-term overfeeding on human gut microbiota in relation to baseline and overfeeding-induced liver steatosis. We also asked whether the baseline microbiota composition is associated to the overfeeding-induced increase in liver fat.<br><br>METHODS: In a randomized trial, 38 overweight and obese subjects were assigned to consume an excess of 1000&#xa0;kcal/day of diets rich in either saturated fat, unsaturated fat, or simple sugars for 3 weeks. Fasting blood samples and [1]H-MR spectroscopy were used for extensive clinical phenotyping as previously reported (PMID: 29844096). Fecal samples were collected for the analysis of the gut microbiota using 16S rRNA amplicon sequencing, imputed metagenomics and qPCR. Microbiota results were correlated with dietary intakes and clinical measurements before and during overfeeding.<br><br>RESULTS: The overall community structure of the microbiota remained highly stable and personalized during overfeeding based on between-sample Bray-Curtis dissimilarity, but the relative abundances of individual taxa were altered in a diet-specific manner: overfeeding saturated fat increased Proteobacteria, while unsaturated fat increased butyrate producers. Sugar overfeeding increased Lactococcus and Escherichia coli. Imputed functions of the gut microbiota were not affected by overfeeding. Several taxa affected by overfeeding significantly correlated with the changes in host metabolic markers. The baseline levels of proteobacterial family Desulfovibrionaceae, and especially genus Bilophila, were significantly associated to overfeeding-induced liver fat increase independently of the diet arm. In general, limited overlap was observed between the overfeeding-induced microbiota changes and the liver fat-associated microbiota features at baseline.<br><br>CONCLUSIONS: Our work indicates that the human gut microbiota is resilient to short-term overfeeding on community level, but specific taxa are altered on diet composition-dependent manner. Generalizable microbiota signatures directly associated with liver steatosis could not be identified. Instead, the carriage of Bilophila was identified as a potential novel risk factor for diet-induced liver steatosis in humans. Clinical trial registry number: NCT02133144 listed on NIH website: ClinicalTrials.gov.}, }
@article {pmid32536356, year = {2020}, author = {Ooi, DS and Tan, CP and Tay, MJ and Ong, SG and Tham, EH and Siah, KTH and Eriksson, JG and Godfrey, KM and Shek, LP and Loo, EX}, title = {Developmental Origins of Health and Disease: Impact of environmental dust exposure in modulating microbiome and its association with non-communicable diseases.}, journal = {Journal of developmental origins of health and disease}, volume = {11}, number = {6}, pages = {545-556}, pmid = {32536356}, issn = {2040-1752}, support = {RG/15/17/31749/BHF_/British Heart Foundation/United Kingdom ; NF-SI-0515-10042/DH_/Department of Health/United Kingdom ; U24 AG047867/AG/NIA NIH HHS/United States ; /BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; MC_UU_12011/4/MRC_/Medical Research Council/United Kingdom ; }, mesh = {*Dust ; Environmental Exposure/*adverse effects ; Female ; Global Burden of Disease ; Global Health ; Humans ; Microbiota/*immunology ; Noncommunicable Diseases/*epidemiology/prevention &amp; control ; Pregnancy ; Prenatal Exposure Delayed Effects/*epidemiology/immunology/microbiology/prevention &amp; control ; Prevalence ; }, abstract = {Non-communicable diseases (NCDs) including obesity, diabetes, and allergy are chronic, multi-factorial conditions that are affected by both genetic and environmental factors. Over the last decade, the microbiome has emerged as a possible contributor to the pathogenesis of NCDs. Microbiome profiles were altered in patients with NCDs, and shift in microbial communities was associated with improvement in these health conditions. Since the genetic component of these diseases cannot be altered, the ability to manipulate the microbiome holds great promise for design of novel therapies in the prevention and treatment of NCDs. Together, the Developmental Origins of Health and Disease concept and the microbial hypothesis propose that early life exposure to environmental stimuli will alter the development and composition of the human microbiome, resulting in health consequences. Recent studies indicated that the environment we are exposed to in early life is instrumental in shaping robust immune development, possibly through modulation of the human microbiome (skin, airway, and gut). Despite much research into human microbiome, the origin of their constituent microbiota remains unclear. Dust (also known as particulate matter) is a key determinant of poor air quality in the modern urban environment. It is ubiquitous and serves as a major source and reservoir of microbial communities that modulates the human microbiome, contributing to health and disease. There are evidence that reported significant associations between environmental dust and NCDs. In this review, we will focus on the impact of dust exposure in shaping the human microbiome and its possible contribution to the development of NCDs.}, }
@article {pmid32533793, year = {2020}, author = {Rotz, SJ and Dandoy, CE}, title = {The microbiome in pediatric oncology.}, journal = {Cancer}, volume = {126}, number = {16}, pages = {3629-3637}, pmid = {32533793}, issn = {1097-0142}, support = {KL2 TR002547/TR/NCATS NIH HHS/United States ; 2KL2TR002547 (PI: Dweik) (SJR)//NIH NCATS/ ; }, mesh = {Child ; Dysbiosis ; High-Throughput Nucleotide Sequencing ; Humans ; Medical Oncology/trends ; Microbiota/*genetics ; Neoplasms/epidemiology/genetics/*microbiology ; Pediatrics ; RNA, Ribosomal, 16S/genetics ; Tumor Microenvironment/*genetics ; }, abstract = {The human microbiome comprises a diverse set of microorganisms, which play a mostly cooperative role in processes such as metabolism and host defense. Next-generation genomic sequencing of bacterial nucleic acids now can contribute a much broader understanding of the diverse organisms composing the microbiome. Emerging evidence has suggested several roles of the microbiome in pediatric hematology/oncology, including susceptibility to infectious diseases, immune response to neoplasia, and contributions to the tumor microenvironment as well as changes to the microbiome from chemotherapy and antibiotics with unclear consequences. In this review, the authors have examined the evidence of the role of the microbiome in pediatric hematology/oncology, discussed how the microbiome may be modulated, and suggested key questions in need of further exploration.}, }
@article {pmid32528717, year = {2020}, author = {Galli, I and Fasanelli, R}, title = {Public understanding of science and common sense: Social representations of the human microbiome among the expert and non-expert public.}, journal = {Health psychology open}, volume = {7}, number = {1}, pages = {2055102920913239}, pmid = {32528717}, issn = {2055-1029}, abstract = {The aim of this investigation is to examine the structure and the content of different social groups' representations of the human microbiome. We employed a non-probabilistic sample comprising two groups of participants. The first group (n = 244) included university students. The second group included lay people (n = 355). We chose a mixed-method approach. The data obtained were processed using IRaMuTeQ software. The results allow us to identify the anchoring and objectification processes activated by the two different groups of interviewees. The results could be useful to those in charge of implementing campaigns aimed at promoting health literacy.}, }
@article {pmid32528434, year = {2020}, author = {Sui, HY and Weil, AA and Nuwagira, E and Qadri, F and Ryan, ET and Mezzari, MP and Phipatanakul, W and Lai, PS}, title = {Impact of DNA Extraction Method on Variation in Human and Built Environment Microbial Community and Functional Profiles Assessed by Shotgun Metagenomics Sequencing.}, journal = {Frontiers in microbiology}, volume = {11}, number = {}, pages = {953}, pmid = {32528434}, issn = {1664-302X}, support = {U01 AI110397/AI/NIAID NIH HHS/United States ; K08 AI123494/AI/NIAID NIH HHS/United States ; R01 AI106878/AI/NIAID NIH HHS/United States ; K23 ES023700/ES/NIEHS NIH HHS/United States ; U01 AI058935/AI/NIAID NIH HHS/United States ; K24 AI106822/AI/NIAID NIH HHS/United States ; R01 AI144119/AI/NIAID NIH HHS/United States ; R56 AI106878/AI/NIAID NIH HHS/United States ; R37 AI106878/AI/NIAID NIH HHS/United States ; }, abstract = {Both the host microbiome and the microbiome of the built environment can have profound impacts on human health. While prior studies have suggested that the variability introduced by DNA extraction method is less than typical biologic variation, most studies have focused on 16S rRNA amplicon sequencing or on high biomass fecal samples. Shotgun metagenomic sequencing provides advantages over amplicon sequencing for surveying the microbiome, but is a challenge to perform in lower microbial biomass samples with high human DNA content such as sputum or vacuumed dust. Here we systematically evaluate the impact of four different extraction methods (phenol:choloroform, and three high-throughput kit-based approaches, the Promega Maxwell gDNA, Qiagen MagAttract PowerSoil DNA, and ZymoBIOMICS 96 MagBead). We report the variation in microbial community structure and predicted microbial function assessed by shotgun metagenomics sequencing in human stool, sputum, and vacuumed dust obtained from ongoing cohort studies or clinical trials. The same beadbeating protocol was used for all samples to focus our evaluation on the impact of kit chemistries on sequencing results. DNA yield was overall highest in the phenol:choloroform and Promega approaches. Only the phenol:choloroform approach showed evidence of contamination in negative controls. Bias was evaluated using mock community controls, and was noted across all extraction methods, although Promega exhibited the least amount of bias. The extraction method did not impact the proportion of human reads, although stool had the lowest proportion of human reads (0.1%) as compared to dust (44.1%) and sputum (80%). We calculated Bray-Curtis dissimilarity and Aitchison distances to evaluate the impact of extraction method on microbial community structure by sample type. Extraction method had the lowest impact in stool (extraction method responsible for 3.0-3.9% of the variability), the most impact in vacuumed dust (12-16% of the variability) and intermediate values for sputum (9.2-12% variability). Similar differences were noted when evaluating microbial community function. Our results will inform investigators planning microbiome studies using diverse sample types in large clinical studies. A consistent DNA extraction approach across all sample types is recommended, particularly with lower microbial biomass samples that are more heavily influenced by extraction method.}, }
@article {pmid32528054, year = {2020}, author = {Fukui, S and Morimoto, S and Ichinose, K and Nakashima, S and Ishimoto, H and Hara, A and Kakugawa, T and Sakamoto, N and Tsuji, Y and Aramaki, T and Koga, T and Kawashiri, SY and Iwamoto, N and Tamai, M and Nakamura, H and Origuchi, T and Ueki, Y and Suzuki, S and Mukae, H and Kawakami, A}, title = {Comparison of lung microbiota between antineutrophil cytoplasmic antibody-associated vasculitis and sarcoidosis.}, journal = {Scientific reports}, volume = {10}, number = {1}, pages = {9466}, pmid = {32528054}, issn = {2045-2322}, mesh = {Aged ; Aged, 80 and over ; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/immunology/*microbiology ; Antibodies, Antineutrophil Cytoplasmic/*immunology ; Bacteria/genetics/*immunology ; Bronchoalveolar Lavage Fluid/immunology/microbiology ; Female ; Humans ; Lung/*immunology/*microbiology ; Male ; Microbiota/genetics/*immunology ; Middle Aged ; RNA, Ribosomal, 16S/genetics ; Sarcoidosis/immunology/*microbiology ; }, abstract = {Microbial involvement in the pathogenesis have been suggested in both antineutrophil cytoplasmic antibody-associated vasculitis (AAV) and sarcoidosis, both of which have lung involvement. However, exhaustive research to assess the bacteria in the lung in AAV and in sarcoidosis have not been performed. We sought to elucidate the distinct dysbiotic lung microbiota between AAV and sarcoidosis. We used 16S rRNA gene high-throughput sequencing to obtain the bacterial community composition of bronchoalveolar lavage fluid (BALF) in patients with AAV (n = 16) compared to patients with sarcoidosis (n = 21). The patients had not undergone therapy with immunosuppressive medication when their BALF was acquired. No difference was observed in α-diversity between patients with AAV and patients with sarcoidosis when using all the detected taxa. We defined the taxa of the oral cavity by using the data of oral microbiota of healthy individuals from the Human Microbiome Project (HMP). The analysis using only oral taxa made the difference in α-diversity between AAV and sarcoidosis clearer compared with those using all the detected taxa. Besides, the analysis using detected taxa except for oral taxa also made the difference in α-diversity between AAV and sarcoidosis clearer compared with those using all the detected taxa. A linear negative relationship between the α-diversity and Birmingham vasculitis activity score (BVAS) was detected in the AAV group. The observed p-value for the effect of the disease groups on the ß-diversity was small while the effect of other factors including sex and smoking status did not have small p-values. By excluding oral taxa from all the detected taxa, we found a cluster mainly consisted of sarcoidosis patients which was characterized with microbial community monopolized by Erythrobacteraceae family. Our results suggested the importance of considering the influence of oral microbiota in evaluating lung microbiota.}, }
@article {pmid32524177, year = {2020}, author = {Dekaboruah, E and Suryavanshi, MV and Chettri, D and Verma, AK}, title = {Human microbiome: an academic update on human body site specific surveillance and its possible role.}, journal = {Archives of microbiology}, volume = {202}, number = {8}, pages = {2147-2167}, pmid = {32524177}, issn = {1432-072X}, mesh = {Computational Biology/*trends ; Disease ; *Human Body ; Humans ; Microbiota/*physiology ; }, abstract = {Human body is inhabited by vast number of microorganisms which form a complex ecological community and influence the human physiology, in the aspect of both health and diseases. These microbes show a relationship with the human immune system based on coevolution and, therefore, have a tremendous potential to contribute to the metabolic function, protection against the pathogen and in providing nutrients and energy. However, of these microbes, many carry out some functions that play a crucial role in the host physiology and may even cause diseases. The introduction of new molecular technologies such as transcriptomics, metagenomics and metabolomics has contributed to the upliftment on the findings of the microbiome linked to the humans in the recent past. These rapidly developing technologies are boosting our capacity to understand about the human body-associated microbiome and its association with the human health. The highlights of this review are inclusion of how to derive microbiome data and the interaction between human and associated microbiome to provide an insight on the role played by the microbiome in biological processes of the human body as well as the development of major human diseases.}, }
@article {pmid32518182, year = {2020}, author = {Topçuoğlu, BD and Lesniak, NA and Ruffin, MT and Wiens, J and Schloss, PD}, title = {A Framework for Effective Application of Machine Learning to Microbiome-Based Classification Problems.}, journal = {mBio}, volume = {11}, number = {3}, pages = {}, pmid = {32518182}, issn = {2150-7511}, support = {P30 DK034933/DK/NIDDK NIH HHS/United States ; R01 CA215574/CA/NCI NIH HHS/United States ; }, mesh = {Colonic Neoplasms/diagnosis ; Feces/microbiology ; Gastrointestinal Diseases/*diagnosis ; Humans ; Linear Models ; Logistic Models ; Machine Learning/*standards ; Microbiota/*genetics ; Predictive Value of Tests ; RNA, Ribosomal, 16S/*genetics ; }, abstract = {Machine learning (ML) modeling of the human microbiome has the potential to identify microbial biomarkers and aid in the diagnosis of many diseases such as inflammatory bowel disease, diabetes, and colorectal cancer. Progress has been made toward developing ML models that predict health outcomes using bacterial abundances, but inconsistent adoption of training and evaluation methods call the validity of these models into question. Furthermore, there appears to be a preference by many researchers to favor increased model complexity over interpretability. To overcome these challenges, we trained seven models that used fecal 16S rRNA sequence data to predict the presence of colonic screen relevant neoplasias (SRNs) (n = 490 patients, 261 controls and 229 cases). We developed a reusable open-source pipeline to train, validate, and interpret ML models. To show the effect of model selection, we assessed the predictive performance, interpretability, and training time of L2-regularized logistic regression, L1- and L2-regularized support vector machines (SVM) with linear and radial basis function kernels, a decision tree, random forest, and gradient boosted trees (XGBoost). The random forest model performed best at detecting SRNs with an area under the receiver operating characteristic curve (AUROC) of 0.695 (interquartile range [IQR], 0.651 to 0.739) but was slow to train (83.2 h) and not inherently interpretable. Despite its simplicity, L2-regularized logistic regression followed random forest in predictive performance with an AUROC of 0.680 (IQR, 0.625 to 0.735), trained faster (12 min), and was inherently interpretable. Our analysis highlights the importance of choosing an ML approach based on the goal of the study, as the choice will inform expectations of performance and interpretability.IMPORTANCE Diagnosing diseases using machine learning (ML) is rapidly being adopted in microbiome studies. However, the estimated performance associated with these models is likely overoptimistic. Moreover, there is a trend toward using black box models without a discussion of the difficulty of interpreting such models when trying to identify microbial biomarkers of disease. This work represents a step toward developing more-reproducible ML practices in applying ML to microbiome research. We implement a rigorous pipeline and emphasize the importance of selecting ML models that reflect the goal of the study. These concepts are not particular to the study of human health but can also be applied to environmental microbiology studies.}, }
@article {pmid32517038, year = {2020}, author = {Leskinen, K and Pajunen, MI and Vilanova, MVG and Kiljunen, S and Nelson, A and Smith, D and Skurnik, M}, title = {YerA41, a Yersinia ruckeri Bacteriophage: Determination of a Non-Sequencable DNA Bacteriophage Genome via RNA-Sequencing.}, journal = {Viruses}, volume = {12}, number = {6}, pages = {}, pmid = {32517038}, issn = {1999-4915}, mesh = {Bacteriophages/classification/*genetics/isolation &amp; purification ; *Genome, Viral ; Phylogeny ; RNA, Viral/genetics ; Sequence Analysis, RNA ; Yersinia ruckeri/*virology ; }, abstract = {YerA41 is a Myoviridae bacteriophage that was originally isolated due its ability to infect Yersinia ruckeri bacteria, the causative agent of enteric redmouth disease of salmonid fish. Several attempts to determine its genomic DNA sequence using traditional and next generation sequencing technologies failed, indicating that the phage genome is modified in such a way that it is an unsuitable template for PCR amplification and for conventional sequencing. To determine the YerA41 genome sequence, we performed RNA-sequencing from phage-infected Y. ruckeri cells at different time points post-infection. The host-genome specific reads were subtracted and de novo assembly was performed on the remaining unaligned reads. This resulted in nine phage-specific scaffolds with a total length of 143 kb that shared only low level and scattered identity to known sequences deposited in DNA databases. Annotation of the sequences revealed 201 predicted genes, most of which found no homologs in the databases. Proteome studies identified altogether 63 phage particle-associated proteins. The RNA-sequencing data were used to characterize the transcriptional control of YerA41 and to investigate its impact on the bacterial gene expression. Overall, our results indicate that RNA-sequencing can be successfully used to obtain the genomic sequence of non-sequencable phages, providing simultaneous information about the phage-host interactions during the process of infection.}, }
@article {pmid32516025, year = {2020}, author = {Satokari, R and Pietilä, L and Mattila, E and Lahtinen, P and Arkkila, PET}, title = {Faecal banking at -20 °C facilitates faecal microbiota transplantation for recurrent Clostridioides difficile infection in clinical practice.}, journal = {Infectious diseases (London, England)}, volume = {52}, number = {9}, pages = {662-665}, doi = {10.1080/23744235.2020.1774075}, pmid = {32516025}, issn = {2374-4243}, mesh = {Aged ; Aged, 80 and over ; Clostridioides difficile/isolation &amp; purification ; Clostridium Infections/diagnosis/*therapy ; Colonoscopy/*methods ; Fecal Microbiota Transplantation/*methods ; Feces/*microbiology ; Female ; Humans ; Male ; Microbiota ; Recurrence ; Retrospective Studies ; Treatment Outcome ; }, }
@article {pmid32515629, year = {2020}, author = {Voth, E and Khanna, S}, title = {The Integrative Human microbiome project: a mile stone in the understanding of the gut microbiome.}, journal = {Expert review of gastroenterology &amp; hepatology}, volume = {14}, number = {8}, pages = {639-642}, doi = {10.1080/17474124.2020.1780912}, pmid = {32515629}, issn = {1747-4132}, mesh = {Diabetes Mellitus/*microbiology ; Dysbiosis/complications ; Female ; Gastrointestinal Microbiome ; Host Microbial Interactions ; Humans ; Inflammatory Bowel Diseases/*microbiology ; Metabolomics ; Microbiota/*physiology ; National Institutes of Health (U.S.) ; Pregnancy ; Pregnancy Complications/microbiology ; United States ; }, }
@article {pmid32514485, year = {2020}, author = {Hahn, A and Burrell, A and Ansusinha, E and Peng, D and Chaney, H and Sami, I and Perez, GF and Koumbourlis, AC and McCarter, R and Freishtat, RJ and Crandall, KA and Zemanick, ET}, title = {Airway microbial diversity is decreased in young children with cystic fibrosis compared to healthy controls but improved with CFTR modulation.}, journal = {Heliyon}, volume = {6}, number = {6}, pages = {e04104}, pmid = {32514485}, issn = {2405-8440}, support = {R21 TR002513/TR/NCATS NIH HHS/United States ; UL1 TR001876/TR/NCATS NIH HHS/United States ; }, abstract = {BACKGROUND: Culture-independent next generation sequencing has identified diverse microbial communities within the cystic fibrosis (CF) airway. The study objective was to test for differences in the upper airway microbiome of children with CF and healthy controls and age-related differences in children with CF.<br><br>METHODS: Oropharyngeal swabs and clinical data were obtained from 25 children with CF and 50 healthy controls aged &#x2264;6 years. Bacterial DNA was amplified and sequenced for the V4 region of 16S rRNA marker-gene. Alpha diversity was measured using operational taxonomic units (OTUs), Shannon diversity, and the inverse Simpson's index. Beta diversity was measured using Morisita-Horn and Bray-Curtis and Jaccard distances. General linear models were used for comparison of alpha diversity measures between groups to account for differences in demographics and exposures. Mixed effects general linear models were used for longitudinal comparisons 1) between children with CF of different ages and 2) between children with CF receiving CF transmembrane conductance regulator (CFTR) modulators, children with CF not receiving CFTR modulators, and healthy controls to adjust for repeated measures per subject.<br><br>RESULTS: Children with CF were more likely to have received antibiotics in the prior year than healthy controls (92% vs 24%, p < 0.001). Controlling age, race, ethnicity, length of breastfeeding, and having siblings, children with CF had a lower richness than healthy controls: OTUs 62.1 vs 83, p = 0.022; and trended toward lower diversity: Shannon 2.09 vs 2.35, p = 0.057; inverse Simpson 5.7 vs 6.92, p = 0.118. Staphylococcus, three Rothia OTUs, and two Streptococcus OTUs were more abundant in CF children versus healthy controls (all p < 0.05). Bray-Curtis and Jaccard distances, which reflect overall microbial community composition, were also significantly different (both p = 0.001). In longitudinally collected samples from children with CF, Morisita-Horn trended toward more similarity in those aged 0-2 years compared to those aged 3-6 years (p = 0.070). In children >2 years of age, there was a significant trend in increasing alpha diversity measures between children with CF not receiving CFTR modulators, children with CF receiving CFTR modulators, and healthy controls: OTUs 63.7 vs 74.7 vs 97.6, p < 0.001; Shannon 2.11 vs 2.34 vs 2.56, p < 0.001; inverse Simpson 5.78 vs 7.23 vs 7.96, p < 0.001.<br><br>CONCLUSIONS: Children with CF have lower bacterial diversity and different composition of organisms compared with healthy controls. This appears to start in early childhood, is possibly related to the use of antibiotics, and may be partially corrected with the use of CFTR modulators.}, }
@article {pmid32514171, year = {2020}, author = {Chng, KR and Li, C and Bertrand, D and Ng, AHQ and Kwah, JS and Low, HM and Tong, C and Natrajan, M and Zhang, MH and Xu, L and Ko, KKK and Ho, EXP and Av-Shalom, TV and Teo, JWP and Khor, CC and ,  and Chen, SL and Mason, CE and Ng, OT and Marimuthu, K and Ang, B and Nagarajan, N}, title = {Cartography of opportunistic pathogens and antibiotic resistance genes in a tertiary hospital environment.}, journal = {Nature medicine}, volume = {26}, number = {6}, pages = {941-951}, pmid = {32514171}, issn = {1546-170X}, support = {MR/L01341X/1/MRC_/Medical Research Council/United Kingdom ; MR/S019669/1/MRC_/Medical Research Council/United Kingdom ; MR/S020810/1/MRC_/Medical Research Council/United Kingdom ; MR/S020810/2/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Beds/microbiology ; Biofilms ; Cross Infection/drug therapy/*microbiology/transmission ; Disinfection ; Drug Resistance, Bacterial/*genetics ; Drug Resistance, Multiple, Bacterial/genetics ; Equipment Contamination ; Equipment and Supplies, Hospital/*microbiology ; Geographic Mapping ; Humans ; *Infection Control ; Metagenomics ; Microbiota/*genetics ; Opportunistic Infections/drug therapy/microbiology/transmission ; Patients' Rooms ; Singapore ; Spatio-Temporal Analysis ; Tertiary Care Centers ; }, abstract = {Although disinfection is key to infection control, the colonization patterns and resistomes of hospital-environment microbes remain underexplored. We report the first extensive genomic characterization of microbiomes, pathogens and antibiotic resistance cassettes in a tertiary-care hospital, from repeated sampling (up to 1.5 years apart) of 179 sites associated with 45 beds. Deep shotgun metagenomics unveiled distinct ecological niches of microbes and antibiotic resistance genes characterized by biofilm-forming and human-microbiome-influenced environments with corresponding patterns of spatiotemporal divergence. Quasi-metagenomics with nanopore sequencing provided thousands of high-contiguity genomes, phage and plasmid sequences (>60% novel), enabling characterization of resistome and mobilome diversity and dynamic architectures in hospital environments. Phylogenetics identified multidrug-resistant strains as being widely distributed and stably colonizing across sites. Comparisons with clinical isolates indicated that such microbes can persist in hospitals for extended periods (>8 years), to opportunistically infect patients. These findings highlight the importance of characterizing antibiotic resistance reservoirs in hospitals and establish the feasibility of systematic surveys to target resources for preventing infections.}, }
@article {pmid32513310, year = {2020}, author = {Douglas, GM and Bielawski, JP and Langille, MGI}, title = {Re-evaluating the relationship between missing heritability and the microbiome.}, journal = {Microbiome}, volume = {8}, number = {1}, pages = {87}, pmid = {32513310}, issn = {2049-2618}, support = {CMF-108026//CIHR/Canada ; }, mesh = {Genetic Variation ; Genome, Human ; *Genome-Wide Association Study ; Humans ; *Microbiota/genetics ; Phenotype ; }, abstract = {Human genome-wide association studies (GWASs) have recurrently estimated lower heritability estimates than familial studies. Many explanations have been suggested to explain these lower estimates, including that a substantial proportion of genetic variation and gene-by-environment interactions are unmeasured in typical GWASs. The human microbiome is potentially related to both of these explanations, but it has been more commonly considered as a source of unmeasured genetic variation. In particular, it has recently been argued that the genetic variation within the human microbiome should be included when estimating trait heritability. We outline issues with this argument, which in its strictest form depends on the holobiont model of human-microbiome interactions. Instead, we argue that the microbiome could be leveraged to help control for environmental variation across a population, although that remains to be determined. We discuss potential approaches that could be explored to determine whether integrating microbiome sequencing data into GWASs is useful. Video abstract.}, }
@article {pmid32513256, year = {2020}, author = {Chopyk, J and Akrami, K and Bavly, T and Shin, JH and Schwanemann, LK and Ly, M and Kalia, R and Xu, Y and Kelley, ST and Malhotra, A and Torriani, FJ and Sweeney, DA and Pride, DT}, title = {Temporal variations in bacterial community diversity and composition throughout intensive care unit renovations.}, journal = {Microbiome}, volume = {8}, number = {1}, pages = {86}, pmid = {32513256}, issn = {2049-2618}, support = {T32 HL134632/HL/NHLBI NIH HHS/United States ; K24 HL132105/HL/NHLBI NIH HHS/United States ; R01 HL085188/HL/NHLBI NIH HHS/United States ; R01 AG063925/AG/NIA NIH HHS/United States ; R01 HL148436/HL/NHLBI NIH HHS/United States ; }, mesh = {Bacteria/genetics ; *Biodiversity ; *Environmental Microbiology ; *Hospital Design and Construction/statistics &amp; numerical data ; *Intensive Care Units ; *Microbiota/genetics ; RNA, Ribosomal, 16S/genetics ; Time Factors ; }, abstract = {BACKGROUND: Inanimate surfaces within a hospital serve as a reservoir of microbial life that may colonize patients and ultimately result in healthcare associated infections (HAIs). Critically ill patients in intensive care units (ICUs) are particularly vulnerable to HAIs. Little is known about how the microbiome of the ICU is established or what factors influence its evolution over time. A unique opportunity to bridge the knowledge gap into how the ICU microbiome evolves emerged in our health system, where we were able to characterize microbial communities in an established hospital ICU prior to closing for renovations, during renovations, and then after re-opening.<br><br>RESULTS: We collected swab specimens from ICU bedrails, computer keyboards, and sinks longitudinally at each renovation stage, and analyzed the bacterial compositions on these surfaces by 16S rRNA gene sequencing. Specimens collected before ICU closure had the greatest alpha diversity, while specimens collected after the ICU had been closed for over 300&#x2009;days had the least. We sampled the ICU during the 45&#x2009;days after re-opening; however, within that time frame, the alpha diversity never reached pre-closure levels. There were clear and significant differences in microbiota compositions at each renovation stage, which was driven by environmental bacteria after closure and human-associated bacteria after re-opening and before closure.<br><br>CONCLUSIONS: Overall, we identified significant differences in microbiota diversity and community composition at each renovation stage. These data help to decipher the evolution of the microbiome in the most critical part of the hospital and demonstrate the significant impacts that microbiota from patients and staff have on the evolution of ICU surfaces. Video Abstract.}, }
@article {pmid32503672, year = {2020}, author = {Liu, Y and Liu, Y and Du, Z and Zhang, L and Chen, J and Shen, Z and Liu, Q and Qin, J and Lv, H and Wang, H and He, L and Liu, J and Huang, Q and Sun, Y and Otto, M and Li, M}, title = {Skin microbiota analysis-inspired development of novel anti-infectives.}, journal = {Microbiome}, volume = {8}, number = {1}, pages = {85}, pmid = {32503672}, issn = {2049-2618}, support = {ZIA AI001080/ImNIH/Intramural NIH HHS/United States ; }, mesh = {Animals ; *Anti-Infective Agents/pharmacology ; *Antibiosis ; Female ; Humans ; Mice ; Mice, Inbred BALB C ; Mice, Inbred ICR ; *Microbiota ; Nanoparticles ; *Skin/microbiology ; Staphylococcal Infections/microbiology ; Staphylococcus aureus ; Staphylococcus hominis/physiology ; Wound Healing ; Wound Infection/microbiology ; }, abstract = {BACKGROUND: The alarming spread of antimicrobial resistance requires the development of novel anti-infective drugs. Despite the recent research focus on the human microbiome and its likely value to understand and exploit inter-bacterial inhibitory phenomena as a source for antimicrobial strategies, the human microbiota has barely been investigated for the purpose of drug development.<br><br>RESULTS: We performed a large screen analyzing over 3000 human skin isolates to evaluate bacterial competition within the human skin microbiota as a basis for the development of anti-infective therapeutics. We discovered a Staphylococcus hominis strain with strong and broad activity against Gram-positive pathogens that was mediated by the bacteriocin micrococcin P1 (MP1). In "probiotic" approaches, this strain led to reduced Staphylococcus aureus infection and accelerated closure of S. aureus-infected wounds. Furthermore, we used a nanoparticle strategy to overcome the physico-chemical limitations often encountered with natural substances such as MP1 and demonstrate a significant reduction of S. aureus infection by MP1-loaded nanoparticles.<br><br>CONCLUSIONS: Our study gives examples of how analysis of bacterial interactions in the human microbiota can be explored for the development of novel, effective anti-infective strategies. Video Abstract.}, }
@article {pmid32498430, year = {2020}, author = {Moles, L and Otaegui, D}, title = {The Impact of Diet on Microbiota Evolution and Human Health. Is Diet an Adequate Tool for Microbiota Modulation?.}, journal = {Nutrients}, volume = {12}, number = {6}, pages = {}, pmid = {32498430}, issn = {2072-6643}, mesh = {Adaptation, Physiological ; *Biological Evolution ; Chronic Disease/*prevention &amp; control ; *Diet ; Ecosystem ; Environment ; Gastrointestinal Microbiome/*physiology ; Host Microbial Interactions/*physiology ; Humans ; Prebiotics ; Probiotics ; }, abstract = {The human microbiome is emerging as an interesting field in research into the prevention of health problems and recovery from illness in humans. The complex ecosystem formed by the microbiota is continuously interacting with its host and the environment. Diet could be assumed to be one of the most prominent factors influencing the microbiota composition. Nevertheless, and in spite of numerous strategies proposed to modulate the human microbiota through dietary means, guidelines to achieve this goal have yet to be established. This review assesses the correlation between social and dietary changes over the course of human evolution and the adaptation of the human microbiota to those changes. In addition, it discusses the main dietary strategies for modulating the microbiota and the difficulties of putting them properly into practice.}, }
@article {pmid32496571, year = {2020}, author = {Wang, CZ and Wan, JY and Wan, J and Wang, S and Luo, Y and Zeng, J and Yao, H and Zhang, CF and Zhang, QH and Sawadogo, WR and Xu, M and Du, W and Qi, LW and Li, P and Yuan, CS}, title = {Human intestinal microbiota derived metabolism signature from a North American native botanical Oplopanax horridus with UPLC/Q-TOF-MS analysis.}, journal = {Biomedical chromatography : BMC}, volume = {34}, number = {10}, pages = {e4911}, doi = {10.1002/bmc.4911}, pmid = {32496571}, issn = {1099-0801}, support = {AT004418//National Institutes of Health/National Center for Complementary and Alternative Medicine (NIH/NCCAM)/ ; B16046//111 Project from the Ministry of Education of China and the State Administration of Foreign Experts Affairs of China/ ; AT005362//National Institutes of Health/National Center for Complementary and Alternative Medicine (NIH/NCCAM)/ ; 81603378//National Natural Science Foundation of China/ ; BK20160545//Natural Science Foundation of Jiangsu Province/ ; }, mesh = {Adult ; Biotransformation ; Chromatography, High Pressure Liquid/methods ; Feces/microbiology ; Gastrointestinal Microbiome/*physiology ; Humans ; Male ; Mass Spectrometry/methods ; Oplopanax/*chemistry ; *Plant Extracts/analysis/chemistry/metabolism ; Polyynes/analysis/metabolism ; Sesquiterpenes/analysis/metabolism ; }, abstract = {Oplopanax horridus, widely distributed in North America, is an herbal medicine traditionally used by Pacific indigenous peoples for various medical conditions. After oral ingestion, constituents in O. horridus extract (OhE) could be converted to their metabolites by the enteric microbiome before absorption. In this study, in order to mimic gut environment, the OhE was biotransformed using the enteric microbiome of healthy human subjects. For accurate and reliable data collection with optimized approaches in sample preparation and analytical conditions, ultra-performance liquid chromatography and quadrupole time-of-flight mass spectrometry were used to characterize parent constituents and their metabolites. In the extract, 20 parent compounds were identified including polyynes, sesquiterpenes, monoterpeondids, phenylpropanoids and phenolic acids. After the biotransformation, a total of 78 metabolites were identified, of which 37 belonged to polyynes metabolites. The common biotransformation pathways are hydroxylation, acetylization, methylation and demethylation. Based on the pathway distributions, the metabolism signature of OhE has been explored. The metabolism pathways of OhE compounds are dependent on their structural classifications and hydrophilic/hydrophobic properties. In summary, with comprehensive analysis, we systematically investigated human microbiome-derived OhE metabolites. The enteric microbial metabolism signature provides novel information for future effective use of O. horridus.}, }
@article {pmid32495698, year = {2020}, author = {Gascon, M and Harrall, KK and Beavers, AW and Glueck, DH and Stanislawski, MA and Alaimo, K and Villalobos, A and Hebert, JR and Dexter, K and Li, K and Litt, J}, title = {Feasibility of collection and analysis of microbiome data in a longitudinal randomized trial of community gardening.}, journal = {Future microbiology}, volume = {15}, number = {8}, pages = {633-648}, pmid = {32495698}, issn = {1746-0921}, support = {P2C HD066613/HD/NICHD NIH HHS/United States ; P30 DK048520/DK/NIDDK NIH HHS/United States ; R25 GM111901/GM/NIGMS NIH HHS/United States ; }, mesh = {Adult ; Bacteria/classification/genetics/isolation &amp; purification ; Feasibility Studies ; Feces/microbiology ; Female ; Forehead/microbiology ; *Gardening ; Health Promotion ; Humans ; Longitudinal Studies ; Male ; *Microbiota ; Middle Aged ; Mouth/microbiology ; Residence Characteristics/statistics &amp; numerical data ; Young Adult ; }, abstract = {Aim: We explored the feasibility of collecting and analyzing human microbiome data in a longitudinal randomized controlled trial of community gardening. Methods &amp; materials: Participants were randomly assigned to gardening (N = 8) or control (N = 8). Participants provided stool, mouth, hand and forehead microbiome samples at six timepoints. Analyses combined mixed models with Qiita output. Results: Participant satisfaction was high, with 75% of participants completing evaluations. While no microbial effects were statistically significant due to small sample size, the analysis pipeline utility was tested. Conclusion: Longitudinal collection and analysis of microbiome data in a community gardening randomized controlled trial is feasible. The analysis pipeline will be useful in larger studies for assessment of the pathway between microbiota, gardening and health outcomes.}, }
@article {pmid32488167, year = {2020}, author = {Rasmussen, MA and Thorsen, J and Dominguez-Bello, MG and Blaser, MJ and Mortensen, MS and Brejnrod, AD and Shah, SA and Hjelmsø, MH and Lehtimäki, J and Trivedi, U and Bisgaard, H and Sørensen, SJ and Stokholm, J}, title = {Ecological succession in the vaginal microbiota during pregnancy and birth.}, journal = {The ISME journal}, volume = {14}, number = {9}, pages = {2325-2335}, pmid = {32488167}, issn = {1751-7370}, mesh = {Bacteria/genetics ; Child ; Female ; Humans ; *Infectious Disease Transmission, Vertical ; Lactobacillus ; *Microbiota ; Pregnancy ; Vagina ; }, abstract = {The mother's vaginal microbiota represents the first microbes to which a child is exposed when delivered vaginally. However, little is known about the composition and development of the vaginal microbiota during pregnancy and birth. Here, we analyzed the vaginal microbiota of 57 women in pregnancy week 24, 36 and at birth after rupture of membranes but before delivery, and further compared the composition with that of the gut and airways of the 1-week-old child. The vaginal community structure had dramatic changes in bacterial diversity and taxonomic distribution, yet carried an individual-specific signature. The relative abundance of most bacterial taxa increased stepwise from week 24 of pregnancy until birth, with a gradual decline of Lactobacillus. Mother-to-child vertical transfer, as suggested by sharing, was modest, with the strongest transfer being for Clostridiales followed by Lactobacillales and Enterobacteriales. In conclusion, late gestation is associated with an increase in maternal vaginal microbiota diversity, and vaginal bacteria at birth only modestly predict the composition of the neonatal microbiota.}, }
@article {pmid32487674, year = {2020}, author = {Brenes, LR and Lohse, MB and Hartooni, N and Johnson, AD}, title = {A Set of Diverse Genes Influence the Frequency of White-Opaque Switching in Candida albicans.}, journal = {G3 (Bethesda, Md.)}, volume = {10}, number = {8}, pages = {2593-2600}, pmid = {32487674}, issn = {2160-1836}, support = {R01 AI049187/AI/NIAID NIH HHS/United States ; }, mesh = {*Candida albicans/genetics/metabolism ; Fungal Proteins/genetics/metabolism ; *Gene Expression Regulation, Fungal ; Genes, Mating Type, Fungal ; Humans ; Phenotype ; Pheromones ; Signal Transduction ; }, abstract = {The fungal species Candida albicans is both a member of the human microbiome and a fungal pathogen. C. albicans undergoes several different morphological transitions, including one called white-opaque switching. Here, cells reversibly switch between two states, "white" and "opaque," and each state is heritable through many cell generations. Each cell type has a distinct cellular and colony morphology and they differ in many other properties including mating, nutritional specialization, and interactions with the innate immune system. Previous genetic screens to gain insight into white-opaque switching have focused on certain classes of genes (for example transcriptional regulators or chromatin modifying enzymes). In this paper, we examined 172 deletion mutants covering a broad range of cell functions. We identified 28 deletion mutants with at least a fivefold effect on switching frequencies; these cover a wide variety of functions ranging from membrane sensors to kinases to proteins of unknown function. In agreement with previous reports, we found that components of the pheromone signaling cascade affect white-to-opaque switching; however, our results suggest that the major effect of Cek1 on white-opaque switching occurs through the cell wall damage response pathway. Most of the genes we identified have not been previously implicated in white-opaque switching and serve as entry points to understand new aspects of this morphological transition.}, }
@article {pmid32486497, year = {2020}, author = {Badawy, S and Pajunen, MI and Haiko, J and Baka, ZAM and Abou-Dobara, MI and El-Sayed, AKA and Skurnik, M}, title = {Identification and Functional Analysis of Temperate Siphoviridae Bacteriophages of Acinetobacter baumannii.}, journal = {Viruses}, volume = {12}, number = {6}, pages = {}, pmid = {32486497}, issn = {1999-4915}, mesh = {Acinetobacter baumannii/*virology ; DNA, Viral/genetics/isolation &amp; purification ; Genome, Viral/genetics ; Lysogeny ; Microscopy, Electron, Transmission ; Phylogeny ; Sequence Analysis, DNA ; Siphoviridae/genetics/isolation &amp; purification/pathogenicity/*physiology ; Viral Plaque Assay ; Virus Activation ; }, abstract = {Acinetobacter baumannii is an opportunistic pathogen that presents a serious clinical challenge due to its increasing resistance to all available antibiotics. Phage therapy has been introduced recently to treat antibiotic-incurable A. baumannii infections. In search for new A. baumannii specific bacteriophages, 20 clinical A. baumannii strains were used in two pools in an attempt to enrich phages from sewage. The enrichment resulted in induction of resident prophage(s) and three temperate bacteriophages, named vB_AbaS_fEg-Aba01, vB_AbaS_fLi-Aba02 and vB_AbaS_fLi-Aba03, all able to infect only one strain (#6597) of the 20 clinical strains, were isolated. Morphological characteristics obtained by transmission electron microscopy together with the genomic information revealed that the phages belong to the family Siphoviridae. The ca. 35 kb genomic sequences of the phages were >99% identical to each other. The linear ds DNA genomes of the phages contained 10 nt cohesive end termini, 52-54 predicted genes, an attP site and one tRNA gene each. A database search revealed an >99% identical prophage in the genome of A.baumannii strain AbPK1 (acc. no. CP024576.1). Over 99% identical prophages were also identified from two of the original 20 clinical strains (#5707 and #5920) and both were shown to be spontaneously inducible, thus very likely being the origins of the isolated phages. The phage vB_AbaS_fEg-Aba01 was also able to lysogenize the susceptible strain #6597 demonstrating that it was fully functional. The phages showed a very narrow host range infecting only two A.baumannii strains. In conclusion, we have isolated and characterized three novel temperate Siphoviridae phages that infect A.baumannii.}, }
@article {pmid32479952, year = {2021}, author = {Singh, A and Nayak, N and Rathi, P and Verma, D and Sharma, R and Chaudhary, A and Agarwal, A and Tripathi, YB and Garg, N}, title = {Microbiome and host crosstalk: A new paradigm to cancer therapy.}, journal = {Seminars in cancer biology}, volume = {70}, number = {}, pages = {71-84}, doi = {10.1016/j.semcancer.2020.05.014}, pmid = {32479952}, issn = {1096-3650}, mesh = {Animals ; Antineoplastic Agents/*administration &amp; dosage ; *Gastrointestinal Microbiome ; *Host Microbial Interactions ; Humans ; Immunomodulation ; Immunotherapy/*methods ; Neoplasms/*drug therapy/immunology/microbiology ; Prebiotics/*administration &amp; dosage ; }, abstract = {The commensal microbiome of humans has co-evolved for thousands of years. The microbiome regulates human health and is also linked to several diseases, including cancer. The advances in next-generation sequencing have significantly contributed to our understanding of the microbiome and its association with cancer and cancer therapy. Recent studies have highlighted a close relationship of the microbiome to the pharmacological effect of chemotherapy and immunotherapy. The chemo-drugs usually interfere with the host immune system and reduces the microbiome diversity inside the body, which in turn leads to decreased efficacy of these drugs. The human microbiome, specifically the gut microbiome, increases the potency of chemo-drugs through metabolism, enzymatic degradation, ecological differences, and immunomodulation. Recent research exploits the involvement of microbiome to shape the efficacy and decrease the toxicity of these chemo-drugs. In this review, we have highlighted the recent development in understanding the relationship of the human microbiome with cancer and also emphasize on various roles of the microbiome in the modulation of cancer therapy. Additionally, we also summarize the ongoing research focussed on the improved efficacy of chemotherapy and immunotherapy using the host microbiome.}, }
@article {pmid32475524, year = {2020}, author = {Dahl, WJ and Rivero Mendoza, D and Lambert, JM}, title = {Diet, nutrients and the microbiome.}, journal = {Progress in molecular biology and translational science}, volume = {171}, number = {}, pages = {237-263}, doi = {10.1016/bs.pmbts.2020.04.006}, pmid = {32475524}, issn = {1878-0814}, mesh = {*Diet ; Humans ; Microbiota/*drug effects ; Nutrients/*administration &amp; dosage/*analysis ; }, abstract = {Although there is associative evidence linking fecal microbiome profile to health and disease, many studies have not considered the confounding effects of dietary intake. Consuming food provides fermentable substrate which sustains the microbial ecosystem that resides with most abundance in the colon. Western, Mediterranean and vegetarian dietary patterns have a role in modulating the gut microbiota, as do trending restrictive diets such the paleolithic and ketogenic. Altering the amount or ratio of carbohydrate, protein and fat, particularly at the extremes of intake, impacts the microbiome. Diets high in fermentable carbohydrates support the relative abundance of Bifidobacterium, Prevotella, Ruminococcus, Dorea and Roseburia, among others, capable of degrading polysaccharides, oligosaccharides and sugars. Conversely, very high fat diets increase bile-resistant organisms such as Bilophila and Bacteroides. Food form, whole foods vs. ultra-processed, alters the provision of macronutrient substrate to the colon due to differing digestibility, and thereby may impact the microbiota and its metabolic activity. In addition, phytochemicals in plant-based foods have specific and possibly prebiotic effects on the microbiome. Further, food ingredients such as certain low-calorie sweeteners enhance Bifidobacterium spp. The weight of evidence to date suggests a high level of interindividual variability in the human microbiome vs. clearly defined, dietary-induced profiles. Healthful dietary patterns, emphasizing plant foods high in microbial-available carbohydrate, support favorable microbiome profiles active in saccharolytic fermentation. Future research into diet and microbiome should consider the balance of gut microbial-generated metabolites, an important link between microbiome profile and human health.}, }
@article {pmid32474160, year = {2020}, author = {Prescott, SL}, title = {A butterfly flaps its wings: Extinction of biological experience and the origins of allergy.}, journal = {Annals of allergy, asthma &amp; immunology : official publication of the American College of Allergy, Asthma, &amp; Immunology}, volume = {125}, number = {5}, pages = {528-534}, pmid = {32474160}, issn = {1534-4436}, mesh = {Allergens/administration &amp; dosage/*immunology ; Betacoronavirus/immunology/pathogenicity ; Biodiversity ; COVID-19 ; Coronavirus Infections/genetics/immunology/*prevention &amp; control/virology ; Disease Susceptibility/*immunology ; Ecosystem ; Environmental Exposure/analysis ; Extinction, Biological ; Gastrointestinal Tract/immunology/microbiology/virology ; Gene-Environment Interaction ; Humans ; Hypersensitivity/genetics/immunology/microbiology/*prevention &amp; control ; Immune System/drug effects ; Microbiota/*immunology ; Pandemics/*prevention &amp; control ; Pneumonia, Viral/genetics/immunology/*prevention &amp; control/virology ; SARS-CoV-2 ; Skin/immunology/microbiology/virology ; }, abstract = {OBJECTIVE: To explore links between biodiversity on all scales and allergic disease as a measure of immune dysregulation.<br><br>DATA SOURCES: PubMed and Web of Science were searched using the keywords biodiversity, nature relatedness, allergic disease, microbiome, noncommunicable diseases, coronavirus disease 2019, and associated terms.<br><br>STUDY SELECTIONS: Studies were selected based on relevance to human health and biodiversity.<br><br>RESULTS: Contact with natural environments enriches the human microbiome, promotes regulated immune responses, and protects against allergy and both acute and chronic inflammatory disorders. These important links to ecopsychological constructs of the extinction of experience, which indicates that loss of direct, personal contact with biodiversity (wildlife and the more visible elements of the natural world), might lead to emotional apathy and irresponsible behaviors toward the environment.<br><br>CONCLUSION: The immune system is a useful early barometer of environmental effects and, by means of the microbiome, is a measure of the way in which our current experiences differ from our ancestral past. Although we would benefit from further research, efforts to increase direct, personal contact with biodiversity have clear benefits for multiple aspects of physical and mental health, the skin and gut microbiome, immune function, food choices, sleep, and physical activity and promote environmental responsibility.}, }
@article {pmid32468338, year = {2020}, author = {Wu, AH and Tseng, C and Vigen, C and Yu, Y and Cozen, W and Garcia, AA and Spicer, D}, title = {Gut microbiome associations with breast cancer risk factors and tumor characteristics: a pilot study.}, journal = {Breast cancer research and treatment}, volume = {182}, number = {2}, pages = {451-463}, pmid = {32468338}, issn = {1573-7217}, support = {20IB-0105//California Breast Cancer Research Program/ ; }, mesh = {Adult ; Age Factors ; Aged ; Bacteroidetes/genetics/isolation &amp; purification ; Biomarkers, Tumor/*metabolism ; Body Mass Index ; Breast/*pathology ; Breast Neoplasms/*epidemiology/pathology/physiopathology ; Cross-Sectional Studies ; DNA, Bacterial/isolation &amp; purification ; Feces/microbiology ; Female ; Firmicutes/genetics/isolation &amp; purification ; Gastrointestinal Microbiome/*physiology ; Humans ; Menarche/physiology ; Middle Aged ; Parity/physiology ; Pilot Projects ; RNA, Ribosomal, 16S/genetics ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Risk Factors ; }, abstract = {OBJECTIVE: To investigate the association between gut microbiome with breast tumor characteristics (receptor status, stage and grade) and known breast cancer risk factors.<br><br>METHODS: In a pilot cross-sectional study of 37 incident breast cancer patients, fecal samples collected prior to chemotherapy were analyzed by 16S ribosomal RNA (rRNA) gene-based sequencing protocol. Alpha diversity and specific taxa by tumor characteristics and breast cancer risk factors were tested by Wilcoxon rank sum test, and by differential abundance analysis, using a zero-inflated negative binomial regression model with adjustment for total counts, age and race/ethnicity.<br><br>RESULTS: There were no significant alpha diversity or phyla differences by estrogen/progesterone&#xa0;receptor status, tumor grade, stage, parity and body mass index. However, women with human epidermal growth factor receptor 2 positive (HER2+) (n&#x2009;=&#x2009;12) compared to HER2- (n&#x2009;=&#x2009;25) breast cancer showed 12-23% lower alpha diversity [number of species (OTU) p&#x2009;=&#x2009;0.033, Shannon index p&#x2009;=&#x2009;0.034], lower abundance of Firmicutes (p&#x2009;=&#x2009;0.005) and higher abundance of Bacteroidetes (p&#x2009;=&#x2009;0.089). Early menarche (ages&#x2009;&#x2264;&#x2009;11) (n&#x2009;=&#x2009;11) compared with later menarche (ages&#x2009;&#x2265;&#x2009;12) (n&#x2009;=&#x2009;26) was associated with lower OTU (p&#x2009;=&#x2009;0.036), Chao1 index (p&#x2009;=&#x2009;0.020) and lower abundance of Firmicutes (p&#x2009;=&#x2009;0.048). High total body fat (TBF) (>&#x2009;46%) (n&#x2009;=&#x2009;12) compared to lower (&#x2264;&#x2009;46%) TBF was also associated with lower Chao 1 index (p&#x2009;=&#x2009;0.011). There were other significant taxa abundance differences by HER2 status, menarche age, as well as other tumor and breast cancer risk factors.<br><br>CONCLUSIONS AND RELEVANCE: Further studies are needed to identify characteristics of the human microbiome and the interrelationships between breast cancer hormone receptor status and established breast cancer risk factors.}, }
@article {pmid32456257, year = {2020}, author = {Vernocchi, P and Del Chierico, F and Putignani, L}, title = {Gut Microbiota Metabolism and Interaction with Food Components.}, journal = {International journal of molecular sciences}, volume = {21}, number = {10}, pages = {}, pmid = {32456257}, issn = {1422-0067}, mesh = {*Diet ; Diet Therapy/methods ; *Gastrointestinal Microbiome ; Host-Pathogen Interactions ; Humans ; Prebiotics/administration &amp; dosage ; Probiotics/therapeutic use ; }, abstract = {The human gut contains trillions of microbes that play a central role in host biology, including the provision of key nutrients from the diet. Food is a major source of precursors for metabolite production; in fact, diet modulates the gut microbiota (GM) as the nutrients, derived from dietary intake, reach the GM, affecting both the ecosystem and microbial metabolic profile. GM metabolic ability has an impact on human nutritional status from childhood. However, there is a wide variability of dietary patterns that exist among individuals. The study of interactions with the host via GM metabolic pathways is an interesting field of research in medicine, as microbiota members produce myriads of molecules with many bioactive properties. Indeed, much evidence has demonstrated the importance of metabolites produced by the bacterial metabolism from foods at the gut level that dynamically participate in various biochemical mechanisms of a cell as a reaction to environmental stimuli. Hence, the GM modulate homeostasis at the gut level, and the alteration in their composition can concur in disease onset or progression, including immunological, inflammatory, and metabolic disorders, as well as cancer. Understanding the gut microbe-nutrient interactions will increase our knowledge of how diet affects host health and disease, thus enabling personalized therapeutics and nutrition.}, }
@article {pmid32453194, year = {2020}, author = {Thapa, S and Runge, JK and Venkatachalam, A and Denne, C and Luna, RA and Anon, JB}, title = {The Nasopharyngeal and Gut Microbiota in Children in a Pediatric Otolaryngology Practice.}, journal = {The Pediatric infectious disease journal}, volume = {39}, number = {9}, pages = {e226-e233}, doi = {10.1097/INF.0000000000002703}, pmid = {32453194}, issn = {1532-0987}, mesh = {Bacteria/classification/*genetics ; Child ; Child, Preschool ; Family Practice/statistics &amp; numerical data ; Female ; Gastrointestinal Microbiome/*genetics ; Humans ; Infant ; Male ; Microbiota/*genetics ; Nasopharynx/*microbiology ; Otolaryngology ; Qualitative Research ; RNA, Ribosomal, 16S/genetics ; }, abstract = {BACKGROUND: The human microbiome evolves rapidly in early life with contributions from various factors such as diet, delivery mode, medical history, antibiotics exposure, genetics, immunomodulators and the environment. A high use of antibiotics in pediatric outpatient settings has been well documented, and improvement in antibiotic selection is required to reduce the risks of antibiotic resistance and disruption of the microbiome.<br><br>METHODS: We performed an exploratory study using 16S rRNA gene-based sequencing to characterize the gut and nasopharyngeal microbiome of children (n = 50) age 1-6 years of age in a pediatric otolaryngology practice.<br><br>RESULTS: Relative abundance of Haemophilus and Moraxella were higher in nasopharyngeal swabs, while Prevotella, Bacteroides, Porphyromonas and Faecalibacterium were highly abundant in rectal swabs. The gut microbiome composition in children <2 years old was different compared with children &#x2265;2 years age. Gut bacterial diversity increased with an increase in age of the children. Children taking probiotics had a notable increase in abundance of potentially beneficial gut bacteria such as Bacteroides and Akkermansia. The nasopharyngeal microbiome differed between children who received antibiotics in the 3 months before sample collection compared with those that did not. Haemophilus spp. was highly abundant in children who received antibiotics 3 months before sampling.<br><br>CONCLUSIONS: The pediatric nasopharyngeal and rectal microbiomes differ in bacterial composition and diversity. The increased abundance of Haemophilus spp. in the nasopharyngeal microbiome of children who received antibiotics during the 3 months before sampling suggests a potential impact of antibiotics in colonization with the otopathogen and may be relevant to clinical practice.}, }
@article {pmid32449747, year = {2020}, author = {Sharma, D and Paterson, AD and Xu, W}, title = {TaxoNN: ensemble of neural networks on stratified microbiome data for disease prediction.}, journal = {Bioinformatics (Oxford, England)}, volume = {36}, number = {17}, pages = {4544-4550}, pmid = {32449747}, issn = {1367-4811}, mesh = {*Diabetes Mellitus, Type 2 ; Humans ; Machine Learning ; *Microbiota ; Neural Networks, Computer ; }, abstract = {MOTIVATION: Research supports the potential use of microbiome as a predictor of some diseases. Motivated by the findings that microbiome data is complex in nature, and there is an inherent correlation due to hierarchical taxonomy of microbial Operational Taxonomic Units (OTUs), we propose a novel machine learning method incorporating a stratified approach to group OTUs into phylum clusters. Convolutional Neural Networks (CNNs) were used to train within each of the clusters individually. Further, through an ensemble learning approach, features obtained from each cluster were then concatenated to improve prediction accuracy. Our two-step approach comprising stratification prior to combining multiple CNNs, aided in capturing the relationships between OTUs sharing a phylum efficiently, as compared to using a single CNN ignoring OTU correlations.<br><br>RESULTS: We used simulated datasets containing 168 OTUs in 200 cases and 200 controls for model testing. Thirty-two OTUs, potentially associated with risk of disease were randomly selected and interactions between three OTUs were used to introduce non-linearity. We also implemented this novel method in two human microbiome studies: (i) Cirrhosis with 118 cases, 114 controls; (ii) type 2 diabetes (T2D) with 170 cases, 174 controls; to demonstrate the model's effectiveness. Extensive experimentation and comparison against conventional machine learning techniques yielded encouraging results. We obtained mean AUC values of 0.88, 0.92, 0.75, showing a consistent increment (5%, 3%, 7%) in simulations, Cirrhosis and T2D data, respectively, against the next best performing method, Random Forest.<br><br>https://github.com/divya031090/TaxoNN_OTU.<br><br>SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.}, }
@article {pmid32446759, year = {2020}, author = {Dannenberg, L and Zikeli, D and Benkhoff, M and Ahlbrecht, S and Kelm, M and Levkau, B and Polzin, A}, title = {Targeting the human microbiome and its metabolite TMAO in cardiovascular prevention and therapy.}, journal = {Pharmacology &amp; therapeutics}, volume = {213}, number = {}, pages = {107584}, doi = {10.1016/j.pharmthera.2020.107584}, pmid = {32446759}, issn = {1879-016X}, mesh = {Animals ; Cardiovascular Diseases/microbiology/*prevention &amp; control/therapy ; Gastrointestinal Microbiome/*physiology ; Humans ; Life Style ; Methylamines/*metabolism ; Microbiota/physiology ; }, abstract = {The human gut microbiota is the most important active part of the intestinal micro-ecosystem. Lifestyle modification, drug intake and nutrition have an impact on the composition of the gut microbiota and its metabolites. This review focuses on the effects of changes in the gut microbiota as well as the important metabolite Trimethylamine-N-oxide (TMAO). Furthermore, relevant therapeutic options to target the human microbiome in patients with cardiovascular disease are presented.}, }
@article {pmid32437658, year = {2020}, author = {Ang, QY and Alexander, M and Newman, JC and Tian, Y and Cai, J and Upadhyay, V and Turnbaugh, JA and Verdin, E and Hall, KD and Leibel, RL and Ravussin, E and Rosenbaum, M and Patterson, AD and Turnbaugh, PJ}, title = {Ketogenic Diets Alter the Gut Microbiome Resulting in Decreased Intestinal Th17 Cells.}, journal = {Cell}, volume = {181}, number = {6}, pages = {1263-1275.e16}, pmid = {32437658}, issn = {1097-4172}, support = {T32 AI060537/AI/NIAID NIH HHS/United States ; R21 CA227232/CA/NCI NIH HHS/United States ; U54 GM104940/GM/NIGMS NIH HHS/United States ; M01 RR001271/RR/NCRR NIH HHS/United States ; P30 DK098722/DK/NIDDK NIH HHS/United States ; R01 HL122593/HL/NHLBI NIH HHS/United States ; P30 DK072476/DK/NIDDK NIH HHS/United States ; K08 AG048354/AG/NIA NIH HHS/United States ; }, mesh = {Adolescent ; Adult ; Animals ; Diet, High-Fat/methods ; Diet, Ketogenic/methods ; Female ; Gastrointestinal Microbiome/*immunology/*physiology ; Humans ; Intestines/*immunology/*microbiology ; Male ; Mice ; Mice, Inbred C57BL ; Microbiota/immunology/physiology ; Middle Aged ; Th17 Cells/*immunology/microbiology/*physiology ; Young Adult ; }, abstract = {Very low-carbohydrate, high-fat ketogenic diets (KDs) induce a pronounced shift in metabolic fuel utilization that elevates circulating ketone bodies; however, the consequences of these compounds for host-microbiome interactions remain unknown. Here, we show that KDs alter the human and mouse gut microbiota in a manner distinct from high-fat diets (HFDs). Metagenomic and metabolomic analyses of stool samples from an 8-week inpatient study revealed marked shifts in gut microbial community structure and function during the KD. Gradient diet experiments in mice confirmed the unique impact of KDs relative to HFDs with a reproducible depletion of bifidobacteria. In vitro and in vivo experiments showed that ketone bodies selectively inhibited bifidobacterial growth. Finally, mono-colonizations and human microbiome transplantations into germ-free mice revealed that the KD-associated gut microbiota reduces the levels of intestinal pro-inflammatory Th17 cells. Together, these results highlight the importance of trans-kingdom chemical dialogs for mediating the host response to dietary interventions.}, }
@article {pmid32435232, year = {2020}, author = {Ma, ZS}, title = {Assessing and Interpreting the Metagenome Heterogeneity With Power Law.}, journal = {Frontiers in microbiology}, volume = {11}, number = {}, pages = {648}, pmid = {32435232}, issn = {1664-302X}, abstract = {There are two major sequencing technologies for investigating the microbiome: the amplicon sequencing that generates the OTU (operational taxonomic unit) tables of marker genes (e.g., bacterial 16S-rRNA), and the metagenomic shotgun sequencing that generates metagenomic gene abundance (MGA) tables. The OTU table is the counterpart of species abundance tables in macrobial ecology of plants and animals, and has been the target of numerous ecological and network analyses in recent gold rush for microbiome research and in great efforts for establishing an inclusive theoretical ecology. Nevertheless, MGA analyses have been largely limited to bioinformatics pipelines and ad hoc statistical methods, and systematic approaches to MGAs guided by classic ecological theories are still few. Here, we argue that, the difference between "gene kinds" and "gene species" are nominal, and the metagenome that a microbiota carries is essentially a 'community' of metagenomic genes (MGs). Each row of a MGA table represents a metagenome of a microbiota, and the whole MGA table represents a 'meta-metagenome' (or an assemblage of metagenomes) of N microbiotas (microbiome samples). Consequently, the same ecological/network analyses used in OTU analyses should be equally applicable to MGA tables. Here we choose to analyze the heterogeneity of metagenome by introducing classic Taylor's power law (TPL) and its recent extensions in community ecology. Heterogeneity is a fundamental property of metagenome, particularly in the context of human microbiomes. Recent studies have shown that the heterogeneity of human metagenomes is far more significant than that of human genomes. Therefore, without deep understanding of the human metagenome heterogeneity, personalized medicine of the human microbiome-associated diseases is hardly feasible. The TPL extensions have been successfully applied to measure the heterogeneity of human microbiome based on amplicon-sequencing reads of marker genes (e.g., 16s-rRNA). In this article, we demonstrate the analysis of the metagenomic heterogeneity of human gut microbiome at whole metagenome scale (with type-I power law extension) and metagenomic gene scale (type-III), as well as the heterogeneity of gene clusters, respectively. We further examine the influences of obesity, IBD and diabetes on the heterogeneity, which is of important ramifications for the diagnosis and treatment of human microbiome-associated diseases.}, }
@article {pmid32431776, year = {2020}, author = {Sewall, JM and Oliver, A and Denaro, K and Chase, AB and Weihe, C and Lay, M and Martiny, JBH and Whiteson, K}, title = {Fiber Force: A Fiber Diet Intervention in an Advanced Course-Based Undergraduate Research Experience (CURE) Course.}, journal = {Journal of microbiology &amp; biology education}, volume = {21}, number = {1}, pages = {}, pmid = {32431776}, issn = {1935-7877}, abstract = {Course-based undergraduate research experiences (CUREs) are an effective way to introduce students to contemporary scientific research. Research experiences have been shown to promote critical thinking, improve understanding and proper use of the scientific method, and help students learn practical skills including writing and oral communication. We aimed to improve scientific training by engaging students enrolled in an upper division elective course in a human microbiome CURE. The "Fiber Force" course is aimed at studying the effect of a wholesome high-fiber diet (40 to 50 g/day for two weeks) on the students' gut microbiomes. Enrolled students participated in a noninvasive diet intervention, designed health surveys, tested hypotheses on the effect of a diet intervention on the gut microbiome, and analyzed their own samples (as anonymized aggregates). The course involved learning laboratory techniques (e.g., DNA extraction, PCR, and 16S sequencing) and the incorporation of computational techniques to analyze microbiome data with QIIME2 and within the R software environment. In addition, the learning objectives focused on effective student performance in writing, data analysis, and oral communication. Enrolled students showed high performance grades on writing, data analysis and oral communication assignments. Pre- and post-course surveys indicate that the students found the experience favorable, increased their interest in science, and heightened awareness of their diet habits. Fiber Force constitutes a validated case of a research experience on microbiology with the capacity to improve research training and promote healthy dietary habits.}, }
@article {pmid32430415, year = {2020}, author = {Gosens, R and Hiemstra, PS and Adcock, IM and Bracke, KR and Dickson, RP and Hansbro, PM and Krauss-Etschmann, S and Smits, HH and Stassen, FRM and Bartel, S}, title = {Host-microbe cross-talk in the lung microenvironment: implications for understanding and treating chronic lung disease.}, journal = {The European respiratory journal}, volume = {56}, number = {2}, pages = {}, pmid = {32430415}, issn = {1399-3003}, mesh = {Humans ; Lung ; *Lung Diseases/therapy ; *Microbiota ; *Respiration Disorders ; *Respiratory Tract Diseases ; }, abstract = {Chronic respiratory diseases are highly prevalent worldwide and will continue to rise in the foreseeable future. Despite intensive efforts over recent decades, the development of novel and effective therapeutic approaches has been slow. However, there is new and increasing evidence that communities of micro-organisms in our body, the human microbiome, are crucially involved in the development and progression of chronic respiratory diseases. Understanding the detailed mechanisms underlying this cross-talk between host and microbiota is critical for development of microbiome- or host-targeted therapeutics and prevention strategies. Here we review and discuss the most recent knowledge on the continuous reciprocal interaction between the host and microbes in health and respiratory disease. Furthermore, we highlight promising developments in microbiome-based therapies and discuss the need to employ more holistic approaches of restoring both the pulmonary niche and the microbial community.}, }
@article {pmid32429141, year = {2020}, author = {Spruit, CM and Wicklund, A and Wan, X and Skurnik, M and Pajunen, MI}, title = {Discovery of Three Toxic Proteins of Klebsiella Phage fHe-Kpn01.}, journal = {Viruses}, volume = {12}, number = {5}, pages = {}, pmid = {32429141}, issn = {1999-4915}, mesh = {Amino Acid Sequence ; Anti-Bacterial Agents/chemistry ; Bacterial Capsules/genetics ; Bacteriophages/classification/isolation &amp; purification/*metabolism/physiology ; Escherichia coli/genetics/growth &amp; development ; Genome, Viral/genetics ; Host Specificity ; Klebsiella pneumoniae/drug effects/genetics/*virology ; Phylogeny ; Podoviridae/classification/isolation &amp; purification/*metabolism/physiology ; Sewage/virology ; Viral Proteins/chemistry/genetics/*toxicity ; Virion/ultrastructure ; beta-Lactam Resistance ; }, abstract = {The lytic phage, fHe-Kpn01 was isolated from sewage water using an extended-spectrum beta-lactamase-producing strain of Klebsiella pneumoniae as a host. The genome is 43,329 bp in size and contains direct terminal repeats of 222 bp. The genome contains 56 predicted genes, of which proteomics analysis detected 29 different proteins in purified phage particles. Comparison of fHe-Kpn01 to other phages, both morphologically and genetically, indicated that the phage belongs to the family Podoviridae and genus Drulisvirus. Because fHe-Kpn01 is strictly lytic and does not carry any known resistance or virulence genes, it is suitable for phage therapy. It has, however, a narrow host range since it infected only three of the 72 tested K. pneumoniae strains, two of which were of capsule type KL62. After annotation of the predicted genes based on the similarity to genes of known function and proteomics results on the virion-associated proteins, 22 gene products remained annotated as hypothetical proteins of unknown function (HPUF). These fHe-Kpn01 HPUFs were screened for their toxicity in Escherichia coli. Three of the HPUFs, encoded by the genes g10, g22, and g38, were confirmed to be toxic.}, }
@article {pmid32426004, year = {2020}, author = {Herman, RA}, title = {Increasing allergy: are antibiotics the elephant in the room?.}, journal = {Allergy, asthma, and clinical immunology : official journal of the Canadian Society of Allergy and Clinical Immunology}, volume = {16}, number = {}, pages = {35}, pmid = {32426004}, issn = {1710-1484}, abstract = {Antibiotics cause dramatic changes to the human microbiome. The composition of the microbiome has been associated with changes in the immune system and these changes are beginning to be linked to immune diseases. Thus, antibiotics have been implicated as a significant contributor to the continual rise of allergies and autoimmune disease in developed countries. This recognition will hopefully result in the development of post-antibiotic therapies that restore a healthy microbiome and reduce immune system disorders.}, }
@article {pmid32414567, year = {2020}, author = {Chipollini, J and Wright, JR and Nwanosike, H and Kepler, CY and Batai, K and Lee, BR and Spiess, PE and Stewart, DB and Lamendella, R}, title = {Characterization of urinary microbiome in patients with bladder cancer: Results from a single-institution, feasibility study.}, journal = {Urologic oncology}, volume = {38}, number = {7}, pages = {615-621}, doi = {10.1016/j.urolonc.2020.04.014}, pmid = {32414567}, issn = {1873-2496}, mesh = {Aged ; Cohort Studies ; Feasibility Studies ; Female ; Humans ; Male ; Microbiota/*physiology ; Prospective Studies ; Urinary Bladder/*pathology ; Urinary Bladder Neoplasms/*microbiology/*urine ; }, abstract = {OBJECTIVES: The human microbiome has been linked to the development of several malignancies, but there is scarcity of data on the microbiome of bladder cancer patients. In this study, we analyzed microbial composition and diversity among patients with and without bladder cancer.<br><br>MATERIAL AND METHODS: Samples were collected from 38 urothelial carcinoma (UC) patients and 10 noncancer controls from August 2018 to May 2019. DNA was extracted and processed for 16 S ribosomal RNA sequencing. Alpha diversity community characteristics including evenness and richness as well as beta diversity metrics were obtained. Linear discriminant analysis effect size was used to identify microbial components whose sequences were more abundant. Pairwise statistics provided quantitative assessment of significant distributions among groups.<br><br>RESULTS: Thirty seven total samples contained high quality sequence data for subsequent analyses and divided into 3 cohorts: control (n&#x202f;=&#x202f;10), muscle-invasive (n&#x202f;=&#x202f;15) and superficial UC (n&#x202f;=&#x202f;12). Control samples had significantly higher species evenness when compared to invasive (P&#x202f;=&#x202f;0.031) and superficial tumors (P&#x202f;=&#x202f;0.002). In addition, higher species richness was observed in noncancer versus cancer samples (Faith phylogenetic diversity, P < 0.05). Significantly enriched taxa were found in both control (Bacteroides, Lachnoclostridium, Burkholderiaceae) and cancer samples (Bacteroides and Faecalbacterium).<br><br>CONCLUSION: Significantly decreased microbial community diversity was seen in the urine of patients with bladder cancer when compared to a noncancer group. Distinct taxa were noted suggesting unique microbial communities in the urine of bladder cancer patients.}, }
@article {pmid32411613, year = {2020}, author = {Pinto, D and Calabrese, FM and De Angelis, M and Celano, G and Giuliani, G and Gobbetti, M and Rinaldi, F}, title = {Predictive Metagenomic Profiling, Urine Metabolomics, and Human Marker Gene Expression as an Integrated Approach to Study Alopecia Areata.}, journal = {Frontiers in cellular and infection microbiology}, volume = {10}, number = {}, pages = {146}, pmid = {32411613}, issn = {2235-2988}, mesh = {*Alopecia Areata/genetics ; Biomarkers ; Gene Expression ; Humans ; Metabolomics ; Scalp ; }, abstract = {Involvement of the microbiome in many different scalp conditions has been investigated over the years. Studies on the role of the scalp microbiome in specific diseases, such as those involving hair growth alterations like non-cicatricial [androgenetic alopecia (AGA), alopecia areata (AA)] and cicatricial alopecia lichen planopilaris, are of major importance. In the present work, we highlighted the differences in microbial populations inhabiting the scalp of AA subjects and a healthy sample cohort by using an integrated approach relying on metagenomic targeted 16S sequencing analysis, urine metabolomics, and human marker gene expression. Significant differences in genera abundances (p < 0.05) were found in the hypodermis and especially the dermis layer. Based on 16S sequencing data, we explored the differences in predicted KEGG pathways and identified some significant differences in predicted pathways related to the AA pathologic condition such as flagellar, assembly, bacterial chemotaxis, mineral absorption, ABC transporters, cellular antigens, glycosaminoglycan degradation, lysosome, sphingolipid metabolism, cell division, protein digestion and absorption, and energy metabolism. All predicted pathways were significantly enhanced in AA samples compared to expression in healthy samples, with the exceptions of mineral absorption, and ABC transporters. We also determined the expression of TNF-α, FAS, KCNA3, NOD-2, and SOD-2 genes and explored the relationships between human gene expression levels and microbiome composition by Pearson's correlation analysis; here, significant correlations both positive (SOD vs. Staphylococcus, Candidatus Aquiluna) and negative (FAS and SOD2 vs. Anaerococcus, Neisseria, and Acinetobacter) were highlighted. Finally, we inspected volatile organic metabolite profiles in urinary samples and detected statistically significant differences (menthol, methanethiol, dihydrodehydro-beta-ionone, 2,5-dimethylfuran, 1,2,3,4, tetrahydro-1,5,7-trimethylnapthalene) when comparing AA and healthy subject groups. This multiple comparison approach highlighted potential traits associated with AA and their relationship with the microbiota inhabiting the scalp, opening up novel therapeutic interventions in such kind of hair growth disorders mainly by means of prebiotics, probiotics, and postbiotics.}, }
@article {pmid32410293, year = {2020}, author = {Qureshi, SS and Kedo, M and Berthrong, ST}, title = {Gender-neutral bathroom surfaces recolonized by microbes more quickly than single-gender bathrooms.}, journal = {Letters in applied microbiology}, volume = {71}, number = {2}, pages = {134-137}, doi = {10.1111/lam.13316}, pmid = {32410293}, issn = {1472-765X}, support = {//Butler University's Center for High Achievement and Scholarly Engagement Honors Program/ ; }, mesh = {Bacteria/classification/*growth &amp; development/isolation &amp; purification ; Bacterial Load/*statistics &amp; numerical data ; Female ; Humans ; Male ; Microbiota/*physiology ; Sex Factors ; Sexual and Gender Minorities/statistics &amp; numerical data ; Toilet Facilities/*statistics &amp; numerical data ; United States ; }, abstract = {As humans become increasingly urban and spend more time inside the built environment, there will be increased interactions between humans and shared public surface microbiomes. Recent cultural changes in the United States have led to increased numbers of gender-neutral bathrooms. Given that bathroom surfaces are frequently sanitized, we used this increased availability of gender-neutral bathrooms to examine how single-gender or gender-neutral surfaces are recolonized with microbes. Given that male and female microbiomes vary, we hypothesized that rates of recolonization would differ between male, female and gender-neutral bathroom surfaces. We collected swabs from common hand-contacted surfaces in bathrooms and cultured microbes on selective and rich media to determine microbial abundance after cleaning. Recolonization was dominated by Gram-positive bacteria and was slowest on male, intermediate on female and fastest on gender-neutral surfaces. These results imply that gender-neutral surfaces approach normal climax microbial communities more quickly than single-gender bathrooms. SIGNIFICANCE OF IMPACT OF THE STUDY: Humans now spend substantial amount of time within the built environment, and as a consequence the human microbiome interacts frequently with indoor surfaces. Social changes are making gender-neutral public bathrooms more common, so it is important to study how humans and microbiomes interact with these bathroom surfaces. We found that the gender-neutral bathroom surfaces recolonize more quickly than single-gender, which suggests that there are more potential human-surface microbiome connections in these public spaces. These results will potentially add a new layer to our understanding of the interactions of humans, our microbiomes and how we design our built environment.}, }
@article {pmid32408372, year = {2020}, author = {Whitmont, RD}, title = {The Human Microbiome, Conventional Medicine, and Homeopathy.}, journal = {Homeopathy : the journal of the Faculty of Homeopathy}, volume = {109}, number = {4}, pages = {248-255}, doi = {10.1055/s-0040-1709665}, pmid = {32408372}, issn = {1476-4245}, mesh = {*Homeopathy ; Humans ; *Medicine ; *Microbiota ; }, abstract = {Human health is intimately linked to the ecology and diversity of the human microbiome. Together, the human organism and the human microbiome work as a complex super-organism throughout the human life cycle. Microbiome science provides direct evidence and substantiation of the fundamental principles of homeopathy, including holism, psychosomatics, direction of cure, the Law of Similars, individuality and susceptibility, minimum dose, and homeostasis. Whilst many conventional (allopathic) medical treatments irreversibly damage the ecology of the microbiome and trigger chronic immune dysfunction and inflammation, the future sustainability of the entire field of medicine depends on the ability to recognize these inconvenient biological truths and to embrace a safer approach based on this evidence. Fortunately, one of the oldest forms of clinically verifiable, evidence-based, and ecologically sustainable medicine, that does not harm the microbiome, already exists in the form of homeopathy.}, }
@article {pmid32407510, year = {2020}, author = {Ma, ZS}, title = {Heterogeneity-disease relationship in the human microbiome-associated diseases.}, journal = {FEMS microbiology ecology}, volume = {96}, number = {7}, pages = {}, doi = {10.1093/femsec/fiaa093}, pmid = {32407510}, issn = {1574-6941}, mesh = {Humans ; *Microbiota ; *Models, Biological ; }, abstract = {Space is a critical and also challenging frontier in human microbiome research. It has been found that lack of consideration of scales beyond individual and ignoring of microbe dispersal are two crucial roadblocks in preventing deep understanding of the spatial heterogeneity of human microbiome. Assessing and interpreting the heterogeneity and dispersal in microbiomes explicitly are particularly challenging, but implicit approaches such as Taylor's power law (TPL) can be rather effective. Based on TPL, which achieved a rare status of ecological laws, we introduce a general methodology for characterizing the spatial heterogeneity of microbiome (i.e. characterization of microbial spatial distribution) and further apply it for investigating the heterogeneity-disease relationship (HDR) via analyzing a big dataset of 26 MAD (microbiome-associated disease) studies covering nearly all high-profile MADs including obesity, diabetes and gout. It was found that in majority of the MAD cases, the microbiome was sufficiently resilient to endure the disease disturbances. Specifically, in ∼10-16% cases, disease effects were significant-the healthy and diseased cohorts exhibited statistically significant differences in the TPL heterogeneity parameters. We further compared HDR with classic diversity-disease relationship (DDR) and explained their mechanistic differences. Both HDR and DDR cross-verified remarkable resilience of the human microbiomes against MADs.}, }
@article {pmid32406914, year = {2021}, author = {Wang, Y and Bhattacharya, T and Jiang, Y and Qin, X and Wang, Y and Liu, Y and Saykin, AJ and Chen, L}, title = {A novel deep learning method for predictive modeling of microbiome data.}, journal = {Briefings in bioinformatics}, volume = {22}, number = {3}, pages = {}, doi = {10.1093/bib/bbaa073}, pmid = {32406914}, issn = {1477-4054}, mesh = {Aging ; Arthritis, Rheumatoid/microbiology ; Cluster Analysis ; Computational Biology/*methods ; *Deep Learning ; Female ; Humans ; Malawi ; Male ; *Microbiota ; *Models, Biological ; Phylogeny ; Sex Factors ; Twin Studies as Topic ; }, abstract = {With the development and decreasing cost of next-generation sequencing technologies, the study of the human microbiome has become a rapid expanding research field, which provides an unprecedented opportunity in various clinical applications such as drug response predictions and disease diagnosis. It is thus essential and desirable to build a prediction model for clinical outcomes based on microbiome data that usually consist of taxon abundance and a phylogenetic tree. Importantly, all microbial species are not uniformly distributed in the phylogenetic tree but tend to be clustered at different phylogenetic depths. Therefore, the phylogenetic tree represents a unique correlation structure of microbiome, which can be an important prior to improve the prediction performance. However, prediction methods that consider the phylogenetic tree in an efficient and rigorous way are under-developed. Here, we develop a novel deep learning prediction method MDeep (microbiome-based deep learning method) to predict both continuous and binary outcomes. Conceptually, MDeep designs convolutional layers to mimic taxonomic ranks with multiple convolutional filters on each convolutional layer to capture the phylogenetic correlation among microbial species in a local receptive field and maintain the correlation structure across different convolutional layers via feature mapping. Taken together, the convolutional layers with its built-in convolutional filters capture microbial signals at different taxonomic levels while encouraging local smoothing and preserving local connectivity induced by the phylogenetic tree. We use both simulation studies and real data applications to demonstrate that MDeep outperforms competing methods in both regression and binary classifications. Availability and Implementation: MDeep software is available at https://github.com/lichen-lab/MDeep Contact:chen61@iu.edu.}, }
@article {pmid32400169, year = {2021}, author = {Salehi, B and Dimitrijević, M and Aleksić, A and Neffe-Skocińska, K and Zielińska, D and Kołożyn-Krajewska, D and Sharifi-Rad, J and Stojanović-Radić, Z and Prabu, SM and Rodrigues, CF and Martins, N}, title = {Human microbiome and homeostasis: insights into the key role of prebiotics, probiotics, and symbiotics.}, journal = {Critical reviews in food science and nutrition}, volume = {61}, number = {9}, pages = {1415-1428}, doi = {10.1080/10408398.2020.1760202}, pmid = {32400169}, issn = {1549-7852}, mesh = {*Gastrointestinal Microbiome ; Homeostasis ; Humans ; Prebiotics ; *Probiotics ; }, abstract = {The interest in the study of the gut microbiome has grown exponentially. Indeed, its impact on health and disease has been increasingly reported, and the importance of keeping gut microbiome homeostasis clearly highlighted. However, and despite many advances, there are still some gaps, as well as the real discernment on the contribution of some species falls far short of what is needed. Anyway, it is already more than a solid fact of its importance in maintaining health and preventing disease, as well as in the treatment of some pathologies. In this sense, and given the existence of some ambiguous opinions, the present review aims to discuss the importance of gut microbiome in homeostasis maintenance, and even the role of probiotics, prebiotics, and symbiotics in both health promotion and disease prevention.}, }
@article {pmid32397233, year = {2020}, author = {Satokari, R}, title = {High Intake of Sugar and the Balance between Pro- and Anti-Inflammatory Gut Bacteria.}, journal = {Nutrients}, volume = {12}, number = {5}, pages = {}, pmid = {32397233}, issn = {2072-6643}, mesh = {*Bacteroidetes ; Cardiovascular Diseases/etiology ; Dietary Sugars/*adverse effects ; Eating/*physiology ; Endotoxemia/etiology ; Endotoxins/metabolism ; Gastrointestinal Microbiome/*physiology ; Heart Disease Risk Factors ; Humans ; Intestinal Mucosa/immunology/*microbiology ; Metabolic Diseases/etiology ; Nutritional Physiological Phenomena/*physiology ; *Proteobacteria ; }, abstract = {The so-called Western diet is rich in saturated fat and sugars and poor in plant-derived fibers, and it is associated with an increased risk of metabolic and cardiovascular diseases, as well as chronic (low grade) inflammation. The detrimental effects of poor diet are in part mediated by gut microbiota, whose composition, functionality and metabolic end products respond to dietary changes. Recent studies have shown that high intake of sugars increase the relative abundance of Proteobacteria in the gut, while simultaneously decreasing the abundance of Bacteroidetes, which can mitigate the effects of endotoxin, as well as reinforce gut barrier function. Thus, a high sugar intake may stagger the balance of microbiota to have increased pro-inflammatory properties and decreased the capacity to regulate epithelial integrity and mucosal immunity. Consequently, high dietary sugar can, through the modulation of microbiota, promote metabolic endotoxemia, systemic (low grade) inflammation and the development of metabolic dysregulation and thereby, high dietary sugar may have many-fold deleterious health effects, in addition to providing excess energy.}, }
@article {pmid32397065, year = {2020}, author = {Bangayan, NJ and Shi, B and Trinh, J and Barnard, E and Kasimatis, G and Curd, E and Li, H}, title = {MG-MLST: Characterizing the Microbiome at the Strain Level in Metagenomic Data.}, journal = {Microorganisms}, volume = {8}, number = {5}, pages = {}, pmid = {32397065}, issn = {2076-2607}, support = {R01GM099530/NH/NIH HHS/United States ; R25 MH109172/MH/NIMH NIH HHS/United States ; UH2AR057503/NH/NIH HHS/United States ; R01 GM099530/GM/NIGMS NIH HHS/United States ; UH2 AR057503/AR/NIAMS NIH HHS/United States ; }, abstract = {The microbiome plays an important role in human physiology. The composition of the human microbiome has been described at the phylum, class, genus, and species levels, however, it is largely unknown at the strain level. The importance of strain-level differences in microbial communities has been increasingly recognized in understanding disease associations. Current methods for identifying strain populations often require deep metagenomic sequencing and a comprehensive set of reference genomes. In this study, we developed a method, metagenomic multi-locus sequence typing (MG-MLST), to determine strain-level composition in a microbial community by combining high-throughput sequencing with multi-locus sequence typing (MLST). We used a commensal bacterium, Propionibacterium acnes, as an example to test the ability of MG-MLST in identifying the strain composition. Using simulated communities, MG-MLST accurately predicted the strain populations in all samples. We further validated the method using MLST gene amplicon libraries and metagenomic shotgun sequencing data of clinical skin samples. MG-MLST yielded consistent results of the strain composition to those obtained from nearly full-length 16S rRNA clone libraries and metagenomic shotgun sequencing analysis. When comparing strain-level differences between acne and healthy skin microbiomes, we demonstrated that strains of RT2/6 were highly associated with healthy skin, consistent with previous findings. In summary, MG-MLST provides a quantitative analysis of the strain populations in the microbiome with diversity and richness. It can be applied to microbiome studies to reveal strain-level differences between groups, which are critical in many microorganism-related diseases.}, }
@article {pmid32393397, year = {2020}, author = {Koh, H and Zhao, N}, title = {A powerful microbial group association test based on the higher criticism analysis for sparse microbial association signals.}, journal = {Microbiome}, volume = {8}, number = {1}, pages = {63}, pmid = {32393397}, issn = {2049-2618}, support = {P30 AI094189/AI/NIAID NIH HHS/United States ; U24 OD023382/OD/NIH HHS/United States ; }, mesh = {*Computational Biology ; Humans ; *Microbiota ; *Software ; }, abstract = {BACKGROUND: In human microbiome studies, it is crucial to evaluate the association between microbial group (e.g., community or clade) composition and a host phenotype of interest. In response, a number of microbial group association tests have been proposed, which account for the unique features of the microbiome data (e.g., high-dimensionality, compositionality, phylogenetic relationship). These tests generally fall in the class of aggregation tests which amplify the overall group association by combining all the underlying microbial association signals, and, therefore, they are powerful when many microbial species are associated with a given host phenotype (i.e., low sparsity). However, in practice, the microbial association signals can be highly sparse, and this is especially the situation where we have a difficulty to discover the microbial group association.<br><br>METHODS: Here, we introduce a powerful microbial group association test for sparse microbial association signals, namely, microbiome higher criticism analysis (MiHC). MiHC is a data-driven omnibus test taken in a search space spanned by tailoring the higher criticism test to incorporate phylogenetic information and/or modulate sparsity levels and including the Simes test for excessively high sparsity levels. Therefore, MiHC robustly adapts to diverse phylogenetic relevance and sparsity levels.<br><br>RESULTS: Our simulations show that MiHC maintains a high power at different phylogenetic relevance and sparsity levels with correct type I error controls. We also apply MiHC to four real microbiome datasets to test the association between respiratory tract microbiome and smoking status, the association between the infant's gut microbiome and delivery mode, the association between the gut microbiome and type 1 diabetes status, and the association between the gut microbiome and human immunodeficiency virus status.<br><br>CONCLUSIONS: In practice, the true underlying association pattern on the extent of phylogenetic relevance and sparsity is usually unknown. Therefore, MiHC can be a useful analytic tool because of its high adaptivity to diverse phylogenetic relevance and sparsity levels. MiHC can be implemented in the R computing environment using our software package freely available at https://github.com/hk1785/MiHC.}, }
@article {pmid32391057, year = {2020}, author = {Thomas, G and Bain, JM and Budge, S and Brown, AJP and Ames, RM}, title = {Identifying Candida albicans Gene Networks Involved in Pathogenicity.}, journal = {Frontiers in genetics}, volume = {11}, number = {}, pages = {375}, pmid = {32391057}, issn = {1664-8021}, support = {MR/M026663/1/MRC_/Medical Research Council/United Kingdom ; MR/M026663/2/MRC_/Medical Research Council/United Kingdom ; MR/N006364/2/MRC_/Medical Research Council/United Kingdom ; }, abstract = {Candida albicans is a normal member of the human microbiome. It is also an opportunistic pathogen, which can cause life-threatening systemic infections in severely immunocompromized individuals. Despite the availability of antifungal drugs, mortality rates of systemic infections are high and new drugs are needed to overcome therapeutic challenges including the emergence of drug resistance. Targeting known disease pathways has been suggested as a promising avenue for the development of new antifungals. However, <30% of C. albicans genes are verified with experimental evidence of a gene product, and the full complement of genes involved in important disease processes is currently unknown. Tools to predict the function of partially or uncharacterized genes and generate testable hypotheses will, therefore, help to identify potential targets for new antifungal development. Here, we employ a network-extracted ontology to leverage publicly available transcriptomics data and identify potential candidate genes involved in disease processes. A subset of these genes has been phenotypically screened using available deletion strains and we present preliminary data that one candidate, PEP8, is involved in hyphal development and immune evasion. This work demonstrates the utility of network-extracted ontologies in predicting gene function to generate testable hypotheses that can be applied to pathogenic systems. This could represent a novel first step to identifying targets for new antifungal therapies.}, }
@article {pmid32391012, year = {2020}, author = {Peroni, DG and Nuzzi, G and Trambusti, I and Di Cicco, ME and Comberiati, P}, title = {Microbiome Composition and Its Impact on the Development of Allergic Diseases.}, journal = {Frontiers in immunology}, volume = {11}, number = {}, pages = {700}, pmid = {32391012}, issn = {1664-3224}, mesh = {Adult ; Animals ; Asthma/*immunology/*microbiology ; Child ; Dermatitis, Atopic/*immunology/*microbiology ; Epidermis/immunology/microbiology ; Food Hypersensitivity/*immunology/*microbiology ; Gastrointestinal Microbiome/*immunology ; Humans ; Immunity ; Respiratory Mucosa/immunology/microbiology ; }, abstract = {Allergic diseases, such as food allergy (FA), atopic dermatitis (AD), and asthma, are heterogeneous inflammatory immune-mediated disorders that currently constitute a public health issue in many developed countries worldwide. The significant increase in the prevalence of allergic diseases reported over the last few years has closely paralleled substantial environmental changes both on a macro and micro scale, which have led to reduced microbial exposure in early life and perturbation of the human microbiome composition. Increasing evidence shows that early life interactions between the human microbiome and the immune cells play a pivotal role in the development of the immune system. Therefore, the process of early colonization by a "healthy" microbiome is emerging as a key determinant of life-long health. In stark contrast, the perturbation of such a process, which results in changes in the host-microbiome biodiversity and metabolic activities, has been associated with greater susceptibility to immune-mediated disorders later in life, including allergic diseases. Here, we outline recent findings on the potential contribution of the microbiome in the gastrointestinal tract, skin, and airways to the development of FA, AD, and asthma. Furthermore, we address how the modulation of the microbiome composition in these different body districts could be a potential strategy for the prevention and treatment of allergic diseases.}, }
@article {pmid32390974, year = {2020}, author = {Jiang, T and Chen, W and Cao, L and He, Y and Zhou, H and Mao, H}, title = {Abundance, Functional, and Evolutionary Analysis of Oxalyl-Coenzyme A Decarboxylase in Human Microbiota.}, journal = {Frontiers in microbiology}, volume = {11}, number = {}, pages = {672}, pmid = {32390974}, issn = {1664-302X}, abstract = {Oxalic acid and its oxalate salts have been linked to kidney stones and other health problems and about 80% kidney stones are made up of calcium oxalate. Oxalyl coenzyme A decarboxylase (OXC) is a key enzyme in the catabolism of oxalate. In this study, we performed bioinformatic and biochemical analysis of OXC. First, we mined the OXC sequences from a public protein database and collected 1396 putative OXC sequences. These sequences were widely spread and mainly distributed in Actinobacteria, Alphaproteobacteria, Gammaproteobacteria, and Betaproteobacteria and classified into seven clusters. The phylogenetic relationship and evolutionary rate of the 7 clusters showed that OXC are highly conserved. Second, the abundance of the different clusters of OXC was explored in 380 human microbiome datasets, which showed that OXCs in Cluster 1 were relatively high in the gut while OXCs in Clusters 2-4 were relatively enriched in the vagina. Third, we measured the activity of one OXC from Mycobacterium mageritense (OXCmm) in Cluster 3, in which there was no experimentally characterized enzymes. Mutation analysis showed that OXCmm shared the same active sites with the OXC from Oxalobacter formigenes. Taken together, this analysis provides a better insight into the distribution and catalysis of OXC and further potential alternative application of OXC active bacteria as probiotics in the management of kidney stone disease.}, }
@article {pmid32384684, year = {2020}, author = {Caparrós-Martín, JA and Flynn, S and Reen, FJ and Woods, DF and Agudelo-Romero, P and Ranganathan, SC and Stick, SM and O'Gara, F}, title = {The Detection of Bile Acids in the Lungs of Paediatric Cystic Fibrosis Patients Is Associated with Altered Inflammatory Patterns.}, journal = {Diagnostics (Basel, Switzerland)}, volume = {10}, number = {5}, pages = {}, pmid = {32384684}, issn = {2075-4418}, support = {FP7-PEOPLE-2013-ITN, 607786//European Comission/ ; FP7-KBBE-2012-6, CP-TP-312184//European Comission/ ; FP7-KBBE-2012-6, 311975//European Comission/ ; OCEAN 2011-2, 287589//European Comission/ ; Marie Curie 256596//European Comission/ ; EU-634486//European Comission/ ; SSPC-2, 12/RC/2275/SFI_/Science Foundation Ireland/Ireland ; SSP3-Pharm5:13/TIDA/B2625/SFI_/Science Foundation Ireland/Ireland ; 12/TIDA/B2411/SFI_/Science Foundation Ireland/Ireland ; 12/TIDA/B2405/SFI_/Science Foundation Ireland/Ireland ; 14/TIDA/2438/SFI_/Science Foundation Ireland/Ireland ; 15/TIDA/2977/SFI_/Science Foundation Ireland/Ireland ; FIRM/RSF/CoFoRD//The Department of Agriculture and Food/ ; FIRM 08/RDC/629//The Department of Agriculture and Food/ ; FIRM 1/F009/MabS//The Department of Agriculture and Food/ ; FIRM 13/F/516//The Department of Agriculture and Food/ ; HRB-ILP-POR-2019-004/HRBI_/Health Research Board/Ireland ; MRCG-2014-6//Health Research Board/Irish Thoracic Society/ ; Beaufort award C2CRA 2007/082//The Marine Institute/ ; Walsh Fellowship 2013//Teagasc/ ; The Glenn Brown Memorial Grant 2017//The Institute for Respiratory Health/ ; MRCG-2018-16/HRBI_/Health Research Board/Ireland ; Grant CFF 1710//US CF Foundation/ ; }, abstract = {Background: Cystic fibrosis (CF) is a hereditary disorder in which persistent unresolved inflammation and recurrent airway infections play major roles in the initiation and progression of the disease. Little is known about triggering factors modulating the transition to chronic microbial infection and inflammation particularly in young children. Cystic fibrosis respiratory disease starts early in life, with the detection of inflammatory markers and infection evident even before respiratory symptoms arise. Thus, identifying factors that dysregulate immune responsiveness at the earliest stages of the disease will provide novel targets for early therapeutic intervention. Methods: We evaluated the clinical significance of bile acid detection in the bronchoalveolar lavage fluid of clinically stable preschool-aged children diagnosed with CF. Results: We applied an unbiased classification strategy to categorize these specimens based on bile acid profiles. We provide clear associations linking the presence of bile acids in the lungs with alterations in the expression of inflammatory markers. Using multiple regression analysis, we also demonstrate that clustering based on bile acid profiles is a meaningful predictor of the progression of structural lung disease. Conclusions: Altogether, our work has identified a clinically relevant host-derived factor that may participate in shaping early events in the aetiology of CF respiratory disease.}, }
@article {pmid32380174, year = {2020}, author = {Price, TK and Lin, H and Gao, X and Thomas-White, KJ and Hilt, EE and Mueller, ER and Wolfe, AJ and Dong, Q and Brubaker, L}, title = {Bladder bacterial diversity differs in continent and incontinent women: a cross-sectional study.}, journal = {American journal of obstetrics and gynecology}, volume = {223}, number = {5}, pages = {729.e1-729.e10}, pmid = {32380174}, issn = {1097-6868}, support = {P20 DK108268/DK/NIDDK NIH HHS/United States ; R01 DK104718/DK/NIDDK NIH HHS/United States ; R21 DK097435/DK/NIDDK NIH HHS/United States ; R56 DK104718/DK/NIDDK NIH HHS/United States ; }, mesh = {Actinomycetaceae/isolation &amp; purification ; Adult ; Aerococcus/isolation &amp; purification ; Aged ; Aged, 80 and over ; *Biodiversity ; Corynebacterium/isolation &amp; purification ; Cross-Sectional Studies ; Female ; Gardnerella vaginalis/isolation &amp; purification ; Humans ; Lactobacillus/isolation &amp; purification ; Lactobacillus crispatus/isolation &amp; purification ; Lactobacillus gasseri/isolation &amp; purification ; *Microbiota ; Middle Aged ; Staphylococcus epidermidis/isolation &amp; purification ; Streptococcus anginosus/isolation &amp; purification ; Urinary Bladder/*microbiology ; Urinary Incontinence, Stress/*microbiology ; Urinary Incontinence, Urge/*microbiology ; Young Adult ; }, abstract = {BACKGROUND: Since the discovery of the bladder microbiome (urobiome), interest has grown in learning whether urobiome characteristics have a role in clinical phenotyping and provide opportunities for novel therapeutic approaches for women with common forms of urinary incontinence.<br><br>OBJECTIVE: This study aimed to test the hypothesis that the bladder urobiome differs among women in the control cohort and women affected by urinary incontinence by assessing associations between urinary incontinence status and the cultured urobiome.<br><br>STUDY DESIGN: With institutional review board oversight, urine specimens from 309 adult women were collected through transurethral catheterization. These women were categorized into 3 cohorts (continent control, stress urinary incontinence [SUI], and urgency urinary incontinence [UUI]) based on their responses to the validated Pelvic Floor Distress Inventory (PFDI) questionnaire. Among 309 women, 150 were in the continent control cohort, 50 were in the SUI cohort, and 109 were in the UUI cohort. Symptom severity was assessed by subscale scoring with the Urinary Distress Inventory (UDI), subscale of the Pelvic Floor Distress Inventory. Microbes were assessed by expanded quantitative urine culture protocol, which detects the most common bladder microbes (bacteria and yeast). Microbes were identified to the species level by matrix-assisted laser desorption and ionization time-of-flight mass spectrometry. Alpha diversity indices were calculated for culture-positive samples and compared across the 3 cohorts. The correlations of UDI scores, alpha diversity indices, and species abundance were estimated.<br><br>RESULTS: Participants had a mean age of 53 years (range 22-90); most were whites (65%). Women with urinary incontinence were slightly older (control, 47; SUI, 54; UUI, 61). By design, UDI symptom scores differed (control, 8.43 [10.1]; SUI, 97.95 [55.36]; UUI, 93.71 [49.12]; P<.001). Among 309 participants, 216 (70%) had expanded quantitative urine culture-detected bacteria; furthermore, the urinary incontinence cohorts had a higher detection frequency than the control cohort (control, 57%; SUI, 86%; UUI, 81%; P<.001). In addition, the most frequently detected species among the cohorts were as follows: continent control, Lactobacillus iners (12.7%), Streptococcus anginosus (12.7%), L crispatus (10.7%), and L gasseri (10%); SUI, S anginosus (26%), L iners (18%), Staphylococcus epidermidis (18%), and L jensenii (16%); and UUI, S anginosus (30.3%), L gasseri (22%), Aerococcus urinae (18.3%), and Gardnerella vaginalis (17.4%). However, only Actinotignum schaalii (formerly Actinobaculum schaalii), A urinae, A sanguinicola, and Corynebacterium lipophile group were found at significantly higher mean abundances in 1 of the urinary incontinence cohorts when compared with the control cohort (Wilcoxon rank sum test; P<.02), and no individual genus differed significantly between the 2 urinary incontinence cohorts. Both urinary incontinence cohorts had increased alpha diversity similar to continent control cohort with indices of species richness, but not evenness, strongly associated with urinary incontinence.<br><br>CONCLUSION: In adult women, the composition of the culturable bladder urobiome is associated with urinary incontinence, regardless of common incontinence subtype. Detection of more unique living microbes was associated with worsening incontinence symptom severity. Culturable species richness was significantly greater in the urinary incontinence cohorts than in the continent control cohort.}, }
@article {pmid32379704, year = {2020}, author = {Liu, S and Wang, Y and Zhao, L and Sun, X and Feng, Q}, title = {Microbiome succession with increasing age in three oral sites.}, journal = {Aging}, volume = {12}, number = {9}, pages = {7874-7907}, pmid = {32379704}, issn = {1945-4589}, mesh = {Adult ; Aged ; *Aging ; Bacteria/*classification ; Biomarkers/metabolism ; Female ; Humans ; Male ; Microbiota/*physiology ; Middle Aged ; Mouth/*microbiology ; Saliva/*microbiology ; }, abstract = {The incidence of oral diseases is remarkably increased with age, and it may be related to oral microbiota. In this study, we systematically investigated the microbiota of gingival crevicular fluid (GCF), tongue back (TB) and saliva (SAL) from various age groups in healthy populations. The microbial diversity results indicated that the α-diversity of bacteria had a tendency to decrease in aging mouth, whereas the β-diversity showed an opposite increasing trend in all three sites. Next, the microbial structure exploration revealed a divergence in bacterial profile in three sites in response to aging, but the intersite differential bacteria demonstrated a uniform bell-shaped variation trend with age. Meanwhile, several age-differentiated genera were shared by GCF, SAL and TB sites, and the bacterial correlation analysis demonstrated a clear shift in the pattern of bacterial correlations with age. Moreover, both the intra- and intersite "core microbiome" showed significantly decreased bacterial diversities with age. Finally, the trending differential bacteria species were used as a biomarker to distinguish the different age groups, and the prediction accuracies in GCF were 0.998, 0.809, 0.668, 0.675 and 0.956. Our results revealed the characteristics of intra- and intersite bacterial succession with age, providing novel insights into senile oral diseases.}, }
@article {pmid32375241, year = {2020}, author = {Tomaiuolo, R and Veneruso, I and Cariati, F and D'Argenio, V}, title = {Microbiota and Human Reproduction: The Case of Female Infertility.}, journal = {High-throughput}, volume = {9}, number = {2}, pages = {}, pmid = {32375241}, issn = {2571-5135}, support = {855720//H2020 Innovation In SMEs/ ; year 2016//EIT Health/ ; }, abstract = {During the last decade, the availability of next-generation sequencing-based approaches has revealed the presence of microbial communities in almost all the human body, including the reproductive tract. As for other body sites, this resident microbiota has been involved in the maintenance of a healthy status. As a consequence, alterations due to internal or external factors may lead to microbial dysbiosis and to the development of pathologies. Female reproductive microbiota has also been suggested to affect infertility, and it may play a key role in the success of assisted reproductive technologies, such as embryo implantation and pregnancy care. While the vaginal microbiota is well described, the uterine microbiota is underexplored. This could be due to technical issues, as the uterus is a low biomass environment. Here, we review the state of the art regarding the role of the female reproductive system microbiota in women's health and human reproduction, highlighting its contribution to infertility.}, }
@article {pmid32374853, year = {2021}, author = {Bartolomaeus, TUP and Birkner, T and Bartolomaeus, H and Löber, U and Avery, EG and Mähler, A and Weber, D and Kochlik, B and Balogh, A and Wilck, N and Boschmann, M and Müller, DN and Markó, L and Forslund, SK}, title = {Quantifying technical confounders in microbiome studies.}, journal = {Cardiovascular research}, volume = {117}, number = {3}, pages = {863-875}, doi = {10.1093/cvr/cvaa128}, pmid = {32374853}, issn = {1755-3245}, mesh = {Adult ; Bacteria/classification/genetics/*isolation &amp; purification ; DNA, Bacterial/genetics/*isolation &amp; purification ; Feces/microbiology ; Female ; *Gastrointestinal Microbiome ; Germany ; Healthy Volunteers ; Humans ; Intestines/*microbiology ; Male ; Middle Aged ; Polymerase Chain Reaction ; RNA, Ribosomal, 16S/genetics/*isolation &amp; purification ; Ribotyping ; *Specimen Handling ; }, abstract = {AIMS: Recent technical developments have allowed the study of the human microbiome to accelerate at an unprecedented pace. Methodological differences may have considerable impact on the results obtained. Thus, we investigated how different storage, isolation, and DNA extraction methods can influence the characterization of the intestinal microbiome, compared to the impact of true biological signals such as intraindividual variability, nutrition, health, and demographics.<br><br>METHODS AND RESULTS: An observative cohort study in 27 healthy subjects was performed. Participants were instructed to collect stool samples twice spaced by a week, using six different methods (naive and Zymo DNA/RNA Shield on dry ice, OMNIgene GUT, RNALater, 95% ethanol, Zymo DNA/RNA Shield at room temperature). DNA extraction from all samples was performed comparatively using QIAamp Power Fecal and ZymoBIOMICS DNA Kits. 16S rRNA sequencing of the gut microbiota as well as qPCRs were performed on the isolated DNA. Metrics included alpha diversity as well as multivariate and univariate comparisons of samples, controlling for covariate patterns computationally. Interindividual differences explained 7.4% of overall microbiome variability, whereas the choice of DNA extraction method explained a further 5.7%. At phylum level, the tested kits differed in their recovery of Gram-positive bacteria, which is reflected in a significantly skewed enterotype distribution.<br><br>CONCLUSION: DNA extraction methods had the highest impact on observed microbiome variability, and were comparable to interindividual differences, thus may spuriously mimic the microbiome signatures of various health and nutrition factors. Conversely, collection methods had a relatively small influence on microbiome composition. The present study provides necessary insight into the technical variables which can lead to divergent results from seemingly similar study designs. We anticipate that these results will contribute to future efforts towards standardization of microbiome quantification procedures in clinical research.}, }
@article {pmid32374655, year = {2020}, author = {Zhu, C and Yuan, C and Wei, FQ and Sun, XY and Zheng, SG}, title = {Intraindividual Variation and Personal Specificity of Salivary Microbiota.}, journal = {Journal of dental research}, volume = {99}, number = {9}, pages = {1062-1071}, doi = {10.1177/0022034520917155}, pmid = {32374655}, issn = {1544-0591}, mesh = {Diet ; Humans ; Longitudinal Studies ; *Microbiota/genetics ; RNA, Ribosomal, 16S/genetics ; *Saliva/microbiology ; }, abstract = {Salivary microbiota is a typical habitat of the human microbiome. This study intended to use salivary microbiota as a model aiming to systematically address the influence of collection methods and temporal dynamics on the human microbiota compared to personal specificity. We carried out a supervised short-term longitudinal study to evaluate the influence of the change of collection methods and sampling time point on salivary microbiota in 10 systemically and orally healthy individuals with certain confounding factors (sex, oral and general health state, medication history, physical exercise, diet, and oral hygiene behavior) controlled before and during the sampling period. The microbial profiles were analyzed by 16S rDNA V3 to V4 hypervariable region amplicon sequencing. The taxonomic structure represented by the dominant species and the weighted UniFrac distance algorithm were used to demonstrate the individual specificity and the intraindividual variation introduced by the change of collection method and sampling time point. The findings suggested individual specificity existed in salivary microbiota from individuals with similar oral and general health status. The intraindividual variation brought by the change of collection method or sampling time point might introduce remarkable perturbation with the personal specificity. Insights into the intraindividual variation and personal specificity of salivary microbiota will enhance our understanding in salivary microbiota-related research. We recommend keeping collection conditions consistent within a study to avoid interference brought by the sampling. The strategy of repeated sampling at multiple time points as representative samples, as well as thorough interpretation of the complex relationships and causality between microbiome composition and disease without the interference of temporal dynamics, is optimal for research exploring the relationship between the salivary microbiome and disease.}, }
@article {pmid32373093, year = {2020}, author = {Woods, DF and Kozak, IM and O'Gara, F}, title = {Microbiome and Functional Analysis of a Traditional Food Process: Isolation of a Novel Species (Vibrio hibernica) With Industrial Potential.}, journal = {Frontiers in microbiology}, volume = {11}, number = {}, pages = {647}, pmid = {32373093}, issn = {1664-302X}, abstract = {Traditional food preservation processes are vital for the food industry. They not only preserve a high-quality protein and nutrient source but can also provide important value-added organoleptic properties. The Wiltshire process is a traditional food curing method applied to meat, and special recognition is given to the maintenance of a live rich microflora within the curing brine. We have previously analyzed a curing brine from this traditional meat process and characterized a unique microbial core signature. The characteristic microbial community is actively maintained and includes the genera, Marinilactibacillus, Carnobacterium, Leuconostoc, and Vibrio. The bacteria present are vital for Wiltshire curing compliance. However, the exact function of this microflora is largely unknown. A microbiome profiling of three curing brines was conducted and investigated for functional traits by the robust bioinformatic tool, Tax4Fun. The key objective was to uncover putative metabolic functions associated with the live brine and to identify changes over time. The functional bioinformatic analysis revealed metabolic enrichments over time, with many of the pathways identified as being involved in organoleptic development. The core bacteria present in the brine are Lactic Acid Bacteria (LAB), with the exception of the Vibrio genus. LAB are known for their positive contribution to food processing, however, little work has been conducted on the use of Vibrio species for beneficial processes. The Vibrio genome was sequenced by Illumina MiSeq technologies and annotated in RAST. A phylogenetic reconstruction was completed using both the 16S rRNA gene and housekeeping genes, gapA, ftsZ, mreB, topA, gyrB, pyrH, recA, and rpoA. The isolated Vibrio species was defined as a unique novel species, named Vibrio hibernica strain B1.19. Metabolic profiling revealed that the bacterium has a unique substrate scope in comparison to other closely related Vibrio species tested. The possible function and industrial potential of the strain was investigated using carbohydrate metabolizing profiling under food processing relevant conditions. Vibrio hibernica is capable of metabolizing a unique carbohydrate profile at low temperatures. This characteristic provides new application options for use in the industrial food sector, as well as highlighting the key role of this bacterium in the Wiltshire curing process.}, }
@article {pmid32372951, year = {2020}, author = {Abdelsalam, NA and Ramadan, AT and ElRakaiby, MT and Aziz, RK}, title = {Toxicomicrobiomics: The Human Microbiome vs. Pharmaceutical, Dietary, and Environmental Xenobiotics.}, journal = {Frontiers in pharmacology}, volume = {11}, number = {}, pages = {390}, pmid = {32372951}, issn = {1663-9812}, abstract = {The harmful impact of xenobiotics on the environment and human health is being more widely recognized; yet, inter- and intraindividual genetic variations among humans modulate the extent of harm, mostly through modulating the outcome of xenobiotic metabolism and detoxification. As the Human Genome Project revealed that host genetic, epigenetic, and regulatory variations could not sufficiently explain the complexity of interindividual variability in xenobiotics metabolism, its sequel, the Human Microbiome Project, is investigating how this variability may be influenced by human-associated microbial communities. Xenobiotic-microbiome relationships are mutual and dynamic. Not only does the human microbiome have a direct metabolizing potential on xenobiotics, but it can also influence the expression of the host metabolizing genes and the activity of host enzymes. On the other hand, xenobiotics may alter the microbiome composition, leading to a state of dysbiosis, which is linked to multiple diseases and adverse health outcomes, including increased toxicity of some xenobiotics. Toxicomicrobiomics studies these mutual influences between the ever-changing microbiome cloud and xenobiotics of various origins, with emphasis on their fate and toxicity, as well the various classes of microbial xenobiotic-modifying enzymes. This review article discusses classic and recent findings in toxicomicrobiomics, with examples of interactions between gut, skin, urogenital, and oral microbiomes with pharmaceutical, food-derived, and environmental xenobiotics. The current state and future prospects of toxicomicrobiomic research are discussed, and the tools and strategies for performing such studies are thoroughly and critically compared.}, }
@article {pmid32369899, year = {2020}, author = {Lee-Sarwar, KA and Lasky-Su, J and Kelly, RS and Litonjua, AA and Weiss, ST}, title = {Metabolome-Microbiome Crosstalk and Human Disease.}, journal = {Metabolites}, volume = {10}, number = {5}, pages = {}, pmid = {32369899}, issn = {2218-1989}, support = {R01HL141826/NH/NIH HHS/United States ; R01 DK125273/DK/NIDDK NIH HHS/United States ; K08 HL148178/NH/NIH HHS/United States ; R01 HL123915/HL/NHLBI NIH HHS/United States ; R01 HL155742/HL/NHLBI NIH HHS/United States ; R01 HL141826/HL/NHLBI NIH HHS/United States ; K08 HL148178/HL/NHLBI NIH HHS/United States ; R01HL123915/NH/NIH HHS/United States ; K01 HL146980/NH/NIH HHS/United States ; UH3OD023268/NH/NIH HHS/United States ; P30 ES001247/ES/NIEHS NIH HHS/United States ; UH3 OD023268/OD/NIH HHS/United States ; K01 HL146980/HL/NHLBI NIH HHS/United States ; }, abstract = {In this review, we discuss the growing literature demonstrating robust and pervasive associations between the microbiome and metabolome. We focus on the gut microbiome, which harbors the taxonomically most diverse and the largest collection of microorganisms in the human body. Methods for integrative analysis of these "omics" are under active investigation and we discuss the advances and challenges in the combined use of metabolomics and microbiome data. Findings from large consortia, including the Human Microbiome Project and Metagenomics of the Human Intestinal Tract (MetaHIT) and others demonstrate the impact of microbiome-metabolome interactions on human health. Mechanisms whereby the microbes residing in the human body interact with metabolites to impact disease risk are beginning to be elucidated, and discoveries in this area will likely be harnessed to develop preventive and treatment strategies for complex diseases.}, }
@article {pmid32366680, year = {2020}, author = {Zhou, X and Johnson, JS and Spakowicz, D and Zhou, W and Zhou, Y and Sodergren, E and Snyder, M and Weinstock, GM}, title = {Longitudinal Analysis of Serum Cytokine Levels and Gut Microbial Abundance Links IL-17/IL-22 With Clostridia and Insulin Sensitivity in Humans.}, journal = {Diabetes}, volume = {69}, number = {8}, pages = {1833-1842}, pmid = {32366680}, issn = {1939-327X}, support = {P30 CA034196/CA/NCI NIH HHS/United States ; P30 DK116074/DK/NIDDK NIH HHS/United States ; }, mesh = {Bayes Theorem ; Firmicutes/physiology ; Gastrointestinal Microbiome/*physiology ; Humans ; Interleukin-17/*blood ; Interleukins/*blood ; Longitudinal Studies ; Microbiota/physiology ; Prediabetic State/immunology/microbiology ; Interleukin-22 ; }, abstract = {Recent studies using mouse models suggest that interaction between the gut microbiome and IL-17/IL-22-producing cells plays a role in the development of metabolic diseases. We investigated this relationship in humans using data from the prediabetes study of the Integrated Human Microbiome Project (iHMP). Specifically, we addressed the hypothesis that early in the onset of metabolic diseases there is a decline in serum levels of IL-17/IL-22, with concomitant changes in the gut microbiome. Clustering iHMP study participants on the basis of longitudinal IL-17/IL-22 profiles identified discrete groups. Individuals distinguished by low levels of IL-17/IL-22 were linked to established markers of metabolic disease, including insulin sensitivity. These individuals also displayed gut microbiome dysbiosis, characterized by decreased diversity, and IL-17/IL-22-related declines in the phylum Firmicutes, class Clostridia, and order Clostridiales This ancillary analysis of the iHMP data therefore supports a link between the gut microbiome, IL-17/IL-22, and the onset of metabolic diseases. This raises the possibility for novel, microbiome-related therapeutic targets that may effectively alleviate metabolic diseases in humans as they do in animal models.}, }
@article {pmid32360945, year = {2020}, author = {Piggott, DA and Tuddenham, S}, title = {The gut microbiome and frailty.}, journal = {Translational research : the journal of laboratory and clinical medicine}, volume = {221}, number = {}, pages = {23-43}, pmid = {32360945}, issn = {1878-1810}, support = {K23 AI125715/AI/NIAID NIH HHS/United States ; P30 AI094189/AI/NIAID NIH HHS/United States ; R01 AG060825/AG/NIA NIH HHS/United States ; }, mesh = {*Frailty ; *Gastrointestinal Microbiome ; HIV Infections/microbiology/physiopathology ; Humans ; }, abstract = {The human microbiome is constituted by an extensive network of organisms that lie at the host/environment interface and transduce signals that play vital roles in human health and disease across the lifespan. Frailty is a critical aging-related syndrome marked by diminished physiological reserve and heightened vulnerability to stress, predictive of major adverse clinical outcomes including death. While recent studies suggest the microbiome may impact key pathways critical to frailty pathophysiology, direct evaluation of the microbiome-frailty relationship remains limited. In this article, we review the complex interplay of biological, behavioral, and environmental factors that may influence shifts in gut microbiome composition and function in aging populations and the putative implications of such shifts for progression to frailty. We discuss HIV infection as a key prototype for elucidating the complex pathways via which the microbiome may precipitate frailty. Finally, we review considerations for future research efforts.}, }
@article {pmid32351023, year = {2020}, author = {Ndika, J and Ilves, M and Kooter, IM and Gröllers-Mulderij, M and Duistermaat, E and Tromp, PC and Kuper, F and Kinaret, P and Greco, D and Karisola, P and Alenius, H}, title = {Mechanistic Similarities between 3D Human Bronchial Epithelium and Mice Lung, Exposed to Copper Oxide Nanoparticles, Support Non-Animal Methods for Hazard Assessment.}, journal = {Small (Weinheim an der Bergstrasse, Germany)}, volume = {16}, number = {36}, pages = {e2000527}, doi = {10.1002/smll.202000527}, pmid = {32351023}, issn = {1613-6829}, mesh = {*Animal Testing Alternatives/methods/standards ; Animals ; *Copper/toxicity ; *Epithelial Cells/drug effects ; Humans ; *Lung/drug effects ; *Metal Nanoparticles/toxicity ; Mice ; Models, Animal ; *Toxicology/methods ; }, abstract = {The diversity and increasing prevalence of products derived from engineered nanomaterials (ENM), warrants implementation of non-animal approaches to health hazard assessment for ethical and practical reasons. Although non-animal approaches are becoming increasingly popular, there are almost no studies of side-by-side comparisons with traditional in vivo assays. Here, transcriptomics is used to investigate mechanistic similarities between healthy/asthmatic models of 3D air-liquid interface (ALI) cultures of donor-derived human bronchial epithelia cells, and mouse lung tissue, following exposure to copper oxide ENM. Only 19% of mouse lung genes with human orthologues are not expressed in the human 3D ALI model. Despite differences in taxonomy and cellular complexity between the systems, a core subset of matching genes cluster mouse and human samples strictly based on ENM dose (exposure severity). Overlapping gene orthologue pairs are highly enriched for innate immune functions, suggesting an important and maybe underestimated role of epithelial cells. In conclusion, 3D ALI models based on epithelial cells, are primed to bridge the gap between traditional 2D in vitro assays and animal models of airway exposure, and transcriptomics appears to be a unifying dose metric that links in vivo and in vitro test systems.}, }
@article {pmid32350240, year = {2020}, author = {Xiao, J and Fiscella, KA and Gill, SR}, title = {Oral microbiome: possible harbinger for children's health.}, journal = {International journal of oral science}, volume = {12}, number = {1}, pages = {12}, pmid = {32350240}, issn = {2049-3169}, support = {K23 DE027412/DE/NIDCR NIH HHS/United States ; }, mesh = {Child ; *Child Health ; Humans ; Infant ; *Microbiota ; Mouth/*microbiology ; }, abstract = {The human microbiome functions as an intricate and coordinated microbial network, residing throughout the mucosal surfaces of the skin, oral cavity, gastrointestinal tract, respiratory tract, and reproductive system. The oral microbiome encompasses a highly diverse microbiota, consisting of over 700 microorganisms, including bacteria, fungi, and viruses. As our understanding of the relationship between the oral microbiome and human health has evolved, we have identified a diverse array of oral and systemic diseases associated with this microbial community, including but not limited to caries, periodontal diseases, oral cancer, colorectal cancer, pancreatic cancer, and inflammatory bowel syndrome. The potential predictive relationship between the oral microbiota and these human diseases suggests that the oral cavity is an ideal site for disease diagnosis and development of rapid point-of-care tests. The oral cavity is easily accessible with a non-invasive collection of biological samples. We can envision a future where early life salivary diagnostic tools will be used to predict and prevent future disease via analyzing and shaping the infant's oral microbiome. In this review, we present evidence for the establishment of the oral microbiome during early childhood, the capability of using childhood oral microbiome to predict future oral and systemic diseases, and the limitations of the current evidence.}, }
@article {pmid32343000, year = {2020}, author = {Lahtinen, P and Jalanka, J and Hartikainen, A and Mattila, E and Hillilä, M and Punkkinen, J and Koskenpato, J and Anttila, VJ and Tillonen, J and Satokari, R and Arkkila, P}, title = {Randomised clinical trial: faecal microbiota transplantation versus autologous placebo administered via colonoscopy in irritable bowel syndrome.}, journal = {Alimentary pharmacology &amp; therapeutics}, volume = {51}, number = {12}, pages = {1321-1331}, doi = {10.1111/apt.15740}, pmid = {32343000}, issn = {1365-2036}, mesh = {Adolescent ; Adult ; Aged ; Colonoscopy/*methods ; Double-Blind Method ; Dysbiosis/complications/microbiology/therapy ; *Fecal Microbiota Transplantation/adverse effects ; Feces/microbiology ; Female ; Follow-Up Studies ; Gastrointestinal Microbiome/physiology ; Humans ; Irritable Bowel Syndrome/complications/microbiology/*therapy ; Male ; Middle Aged ; Placebos ; Quality of Life ; Transplantation, Autologous ; Treatment Outcome ; Young Adult ; }, abstract = {BACKGROUND: Irritable bowel syndrome (IBS) has been associated with microbial dysbiosis.<br><br>AIM: To investigate the efficacy of faecal microbiota transplantation (FMT) in the treatment of IBS.<br><br>METHODS: Forty-nine IBS patients were randomised to receive autologous or allogenic FMT via colonoscopy. The primary endpoint was a sustained, minimum of 50-point, reduction in the IBS Symptom Severity Score. The secondary outcomes were levels of anxiety and depression, changes in quality of life, gut microbiota and faecal water content as assessed with validated questionnaires, intestinal microbiota composition and stool dry weight.<br><br>RESULTS: The primary endpoint was not achieved in either group. However, there was a transient reduction in the mean IBS Symptom Severity Score in the FMT group at 12&#xa0;weeks after treatment as compared to baseline (P&#xa0;=&#xa0;0.01). The groups did not differ in the number of patients achieving clinical response at 12&#xa0;weeks. In the FMT-treated patients, microbial composition had changed to resemble that of the donor and the stool water content decreased significantly compared to baseline. The depression score decreased in patients with a reduction in IBS symptoms after FMT, but not in those placebo-treated patients who experienced a reduction in IBS symptoms.<br><br>CONCLUSIONS: FMT provided only a transient relief of symptoms, although it induced a sustained alteration in the microbiota of IBS patients. Therefore, FMT delivered by a single infusion via colonoscopy cannot be recommended as a treatment for IBS in clinical practice. ClinicalTrials.Org, Trial registration number: NCT03561519.}, }
@article {pmid32340923, year = {2019}, author = {Gotschlich, EC and Colbert, RA and Gill, T}, title = {Methods in microbiome research: Past, present, and future.}, journal = {Best practice &amp; research. Clinical rheumatology}, volume = {33}, number = {6}, pages = {101498}, pmid = {32340923}, issn = {1532-1770}, support = {ZIA AR041184/ImNIH/Intramural NIH HHS/United States ; }, mesh = {Dysbiosis ; Humans ; *Microbiota ; Research/trends ; }, abstract = {The human microbiome is impressively immense and participates in many aspects of our health and wellness, particularly involving the development and maintenance of a healthy immune system. Not only do our microbes teach the immune system to fight infection, they also teach immune tolerance and help maintain homeostasis. From this knowledge, we have learned that the loss of tolerance to microbiota in both innate and adaptive processes plays an important role in immune-mediated and autoimmune disease. In this chapter, we will be discussing about methods used to study the microbiome, both old and new methods, fundamental concepts that have taken hold within the field, and how these principles relate to rheumatology, including thoughts on how microbiome research may be focused in the next decade.}, }
@article {pmid32334114, year = {2020}, author = {Zhou, J and Sun, T and Kang, W and Tang, D and Feng, Q}, title = {Pathogenic and antimicrobial resistance genes in Streptococcus oralis strains revealed by comparative genome analysis.}, journal = {Genomics}, volume = {112}, number = {5}, pages = {3783-3793}, doi = {10.1016/j.ygeno.2020.04.014}, pmid = {32334114}, issn = {1089-8646}, mesh = {Anti-Bacterial Agents/pharmacology ; *Comparative Genomic Hybridization ; Drug Resistance, Bacterial/*genetics ; *Genes, Bacterial ; RNA, Ribosomal, 16S/genetics ; Streptococcus oralis/drug effects/*genetics ; Virulence Factors/genetics ; }, abstract = {Streptococcus oralis is an early colonizer bacterium in dental plaques and is considered a potential pathogen of infective endocarditis (IE) disease. In this study, we built a complete genome map of Streptococcus oralis strain SOT, Streptococcus oralis strain SOD and Streptococcus infantis strain SO and performed comparative genomic analysis among these three strains. The results showed that there are five genomic islands (GIs) in strain SOT and one CRISPR in strain SOD. Each genome harbors various pathogenic genes related to diseases and drug resistance, while the antibiotic resistance genes in strains SOT and SOD were quite similar but different from those in strain SO. In addition, we identified 17 main virulence factors and capsule-related genes in three strains. These results suggest the pathogenic potential of Streptococcus strains, which lay a foundation for the prevention and treatment of a Streptococcus oralis infection.}, }
@article {pmid32332073, year = {2020}, author = {Manasson, J and Blank, RB and Scher, JU}, title = {The microbiome in rheumatology: Where are we and where should we go?.}, journal = {Annals of the rheumatic diseases}, volume = {79}, number = {6}, pages = {727-733}, doi = {10.1136/annrheumdis-2019-216631}, pmid = {32332073}, issn = {1468-2060}, support = {R01 AR074500/AR/NIAMS NIH HHS/United States ; }, mesh = {Autoimmune Diseases/drug therapy/*microbiology ; Biomedical Research ; Humans ; *Microbiota ; Rheumatic Diseases/drug therapy/*microbiology ; }, abstract = {From birth, humans coexist and coevolve with trillions of micro-organisms inhabiting most body surfaces and cavities, referred to as the human microbiome. Advances in sequencing technologies and computational methods have propelled the exploration of the microbiome's contribution to human health and disease, spearheaded by massive efforts such as the Human Microbiome Project and the Europe-based MetaHit Consortium. Yet, despite the accumulated body of literature and a growing awareness among patients, microbiome research in rheumatology has not had a key impact on clinical practice. Herein, we describe some of the landmark microbiome studies in autoimmunity and rheumatology, the challenges and opportunities of microbiome research and how to navigate them, advances in related fields that have overcome these pitfalls, and future directions of harnessing the microbiome for diagnostic and therapeutic purposes.}, }
@article {pmid32329665, year = {2020}, author = {Jia, B and Park, D and Hahn, Y and Jeon, CO}, title = {Metagenomic analysis of the human microbiome reveals the association between the abundance of gut bile salt hydrolases and host health.}, journal = {Gut microbes}, volume = {11}, number = {5}, pages = {1300-1313}, pmid = {32329665}, issn = {1949-0984}, mesh = {Amidohydrolases/chemistry/classification/*metabolism ; Bacteria/*enzymology ; Bile Acids and Salts/*metabolism ; Cardiovascular Diseases/enzymology/microbiology ; Diabetes Mellitus, Type 2/enzymology/microbiology ; Gastrointestinal Diseases/enzymology/microbiology ; Gastrointestinal Microbiome/*physiology ; Gastrointestinal Tract/*microbiology ; Humans ; Liver Diseases/enzymology/microbiology ; Metagenome ; Metagenomics ; Microbiota/*physiology ; Nervous System Diseases/enzymology/microbiology ; Phylogeny ; }, abstract = {Bile acid metabolism by the gut microbiome exerts both beneficial and harmful effects on host health. Microbial bile salt hydrolases (BSHs), which initiate bile acid metabolism, exhibit both positive and negative effects on host physiology. In this study, 5,790 BSH homologs were collected and classified into seven clusters based on a sequence similarity network. Next, the abundance and distribution of BSH in 380 metagenomes from healthy participants were analyzed. It was observed that different clusters occupied diverse ecological niches in the human microbiome and that the clusters with signal peptides were relatively abundant in the gut. Then, the association between BSH clusters and 12 human diseases was analyzed by comparing the abundances of BSH genes in patients (n = 1,605) and healthy controls (n = 1,540). The analysis identified a significant association between BSH gene abundance and 10 human diseases, including gastrointestinal diseases, obesity, type 2 diabetes, liver diseases, cardiovascular diseases, and neurological diseases. The associations were further validated by separate cohorts with inflammatory bowel diseases and colorectal cancer. These large-scale studies of enzyme sequences combined with metagenomic data provide a reproducible assessment of the association between gut BSHs and human diseases. This information can contribute to future diagnostic and therapeutic applications of BSH-active bacteria for improving human health.}, }
@article {pmid32327694, year = {2020}, author = {Yang, H and Zhang, J and Xue, Z and Zhao, C and Lei, L and Wen, Y and Dong, Y and Yang, J and Zhang, L}, title = {Potential Pathogenic Bacteria in Seminal Microbiota of Patients with Different Types of Dysspermatism.}, journal = {Scientific reports}, volume = {10}, number = {1}, pages = {6876}, pmid = {32327694}, issn = {2045-2322}, mesh = {Adult ; Asthenozoospermia/microbiology ; Bacteria/metabolism/pathogenicity ; Biodiversity ; Biomarkers/metabolism ; Case-Control Studies ; Discriminant Analysis ; Humans ; Infertility, Male/*microbiology ; Male ; Metagenome ; *Microbiota/genetics ; Oligospermia/microbiology ; Phylogeny ; Principal Component Analysis ; Semen/*microbiology ; }, abstract = {Human microbiota play an important role in the health of their human hosts. Recent studies have demonstrated that microbiota exist in seminal plasma. The current study aims to elucidate whether seminal microbiota exist in patients with different types of dysspermatism and whether bacterial biomarkers can be identified for them. A total of 159 study participants were recruited, including 22 patients with oligoasthenospermia, 58 patients with asthenospermia, 8 patients with azoospermia, 13 patients with oligospermia, and 58 matched healthy controls. Seminal microbiota composition was analyzed using 16S rRNA gene-based sequencing. The results showed that the composition of seminal microbiota of patients with dysspermatism differed from those of healthy controls. Comparison of the microbiota composition in semen samples from patients with different types of dysspermatism showed that microbiota in patients with asthenospermia and oligoasthenospermia were distinct from healthy controls in beta diversity (P < 0.05). Characteristic biomarkers, including Ureaplasma, Bacteroides, Anaerococcus, Finegoldia, Lactobacillus and Acinetobacter lwoffii, were identified based on LEfSe analysis. Inferred functional analysis based on seminal microbiome data further indicated the presence of potential pathogenic biomarkers in patients with asthenospermia and oligoasthenospermia. These results provided profiles of seminal microbiota exhibited in different types of dysspermatism, thus providing new insights into their pathogenesis.}, }
@article {pmid32326394, year = {2020}, author = {Garcia-Mazcorro, JF and Minamoto, Y and Kawas, JR and Suchodolski, JS and de Vos, WM}, title = {Akkermansia and Microbial Degradation of Mucus in Cats and Dogs: Implications to the Growing Worldwide Epidemic of Pet Obesity.}, journal = {Veterinary sciences}, volume = {7}, number = {2}, pages = {}, pmid = {32326394}, issn = {2306-7381}, abstract = {Akkermansia muciniphila is a mucin-degrading bacterium that has shown the potential to provide anti-inflammatory and anti-obesity effects in mouse and man. We here focus on companion animals, specifically cats and dogs, and evaluate the microbial degradation of mucus and its health impact in the context of the worldwide epidemic of pet obesity. A literature survey revealed that the two presently known Akkermansia spp., A. muciniphila and A. glycaniphila, as well as other members of the phylum of Verrucomicrobia seem to be neither very prevalent nor abundant in the digestive tract of cats and dog. While this may be due to methodological aspects, it suggests that bacteria related to Akkermansia are not the major mucus degraders in these pets and hence other mucus-utilizing taxa may deserve attention. Hence, we will discuss the potential of these endogenous mucus utilizers and dietary interventions to boost these as well as the use of Akkermansia spp. related bacteria or their components as strategies to target feline and canine obesity.}, }
@article {pmid32324967, year = {2020}, author = {Samples, RM and Balunas, MJ}, title = {Bridging the Gap: Plant-Endophyte Interactions as a Roadmap to Understanding Small-Molecule Communication in Marine Microbiomes.}, journal = {Chembiochem : a European journal of chemical biology}, volume = {21}, number = {19}, pages = {2708-2721}, doi = {10.1002/cbic.202000064}, pmid = {32324967}, issn = {1439-7633}, mesh = {Endophytes/chemistry/*metabolism ; Humans ; Microbiota ; Plants/*chemistry/metabolism ; Small Molecule Libraries/chemistry/*metabolism ; }, abstract = {Probing the composition of the microbiome and its association with health and disease states is more accessible than ever due to the rise of affordable sequencing technology. Despite advances in our ability to identify members of symbiont communities, untangling the chemical signaling that they use to communicate with host organisms remains challenging. In order to gain a greater mechanistic understanding of how the microbiome impacts health, and how chemical ecology can be leveraged to advance small-molecule drug discovery from microorganisms, the principals governing communication between host and symbiont must be elucidated. Herein, we review common modes of interkingdom small-molecule communication in terrestrial and marine environments, describe the differences between these environments, and detail the advantages and disadvantages for studies focused on the marine environment. Finally, we propose the use of plant-endophyte interactions as a stepping stone to a greater understanding of similar interactions in marine invertebrates, and ultimately in humans.}, }
@article {pmid32319703, year = {2020}, author = {Vangoitsenhoven, R and Cresci, GAM}, title = {Role of Microbiome and Antibiotics in Autoimmune Diseases.}, journal = {Nutrition in clinical practice : official publication of the American Society for Parenteral and Enteral Nutrition}, volume = {35}, number = {3}, pages = {406-416}, doi = {10.1002/ncp.10489}, pmid = {32319703}, issn = {1941-2452}, support = {R00AA023266//GAC National Institutes of Health, NIAAA/ ; }, mesh = {Animals ; *Anti-Bacterial Agents/adverse effects/therapeutic use ; *Autoimmune Diseases/drug therapy/microbiology/therapy ; Diabetes Mellitus, Type 1/immunology/microbiology ; Dysbiosis/chemically induced/microbiology ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/drug effects/immunology/*physiology ; Humans ; Immune System/drug effects/microbiology/physiology ; Inflammatory Bowel Diseases/immunology/microbiology ; Lymphoid Tissue/immunology/microbiology ; Prebiotics/administration &amp; dosage ; Probiotics/therapeutic use ; }, abstract = {The global rise in the incidence of autoimmune diseases has paralleled the widespread use of antibiotics. Recently, the gut microbiome has been shown to be key in the development and maturation of a normal immune system, and a range of microbial disturbances have been associated with the development and activity of several autoimmune diseases. Here, we aim to provide an overview of the mechanistic crosstalk between the human microbiome, the immune system, and antibiotics. The disease-associated microbial gut dysbiosis, the potential role of antibiotics in the development and treatment of autoimmune diseases, and the manipulation of the gut microbiome with prebiotics and probiotics is discussed using 2 key autoimmune diseases as an example: inflammatory bowel disease and type 1 diabetes. Although some data suggest that widespread use of antibiotics may facilitate autoimmunity through gut dysbiosis, there are also data to suggest antibiotics may hold the potential to improve disease activity. Currently, the effect of fecal microbiota transplantation on several autoimmune diseases is being studied in clinical trials, and several preclinical studies are revealing promising results with probiotic and prebiotic therapies.}, }
@article {pmid32318028, year = {2020}, author = {Eetemadi, A and Rai, N and Pereira, BMP and Kim, M and Schmitz, H and Tagkopoulos, I}, title = {The Computational Diet: A Review of Computational Methods Across Diet, Microbiome, and Health.}, journal = {Frontiers in microbiology}, volume = {11}, number = {}, pages = {393}, pmid = {32318028}, issn = {1664-302X}, abstract = {Food and human health are inextricably linked. As such, revolutionary impacts on health have been derived from advances in the production and distribution of food relating to food safety and fortification with micronutrients. During the past two decades, it has become apparent that the human microbiome has the potential to modulate health, including in ways that may be related to diet and the composition of specific foods. Despite the excitement and potential surrounding this area, the complexity of the gut microbiome, the chemical composition of food, and their interplay in situ remains a daunting task to fully understand. However, recent advances in high-throughput sequencing, metabolomics profiling, compositional analysis of food, and the emergence of electronic health records provide new sources of data that can contribute to addressing this challenge. Computational science will play an essential role in this effort as it will provide the foundation to integrate these data layers and derive insights capable of revealing and understanding the complex interactions between diet, gut microbiome, and health. Here, we review the current knowledge on diet-health-gut microbiota, relevant data sources, bioinformatics tools, machine learning capabilities, as well as the intellectual property and legislative regulatory landscape. We provide guidance on employing machine learning and data analytics, identify gaps in current methods, and describe new scenarios to be unlocked in the next few years in the context of current knowledge.}, }
@article {pmid32316935, year = {2020}, author = {Koliada, A and Moseiko, V and Romanenko, M and Piven, L and Lushchak, O and Kryzhanovska, N and Guryanov, V and Vaiserman, A}, title = {Seasonal variation in gut microbiota composition: cross-sectional evidence from Ukrainian population.}, journal = {BMC microbiology}, volume = {20}, number = {1}, pages = {100}, pmid = {32316935}, issn = {1471-2180}, mesh = {Adolescent ; Adult ; Bacteria/*classification/genetics/isolation &amp; purification ; Berberine Alkaloids ; Child ; Child, Preschool ; Cross-Sectional Studies ; Feces/*microbiology ; Female ; Gastrointestinal Microbiome ; Humans ; Infant ; Infant, Newborn ; Life Style ; Longitudinal Studies ; Male ; Middle Aged ; Phenanthridines ; Phylogeny ; RNA, Ribosomal, 16S/*genetics ; Real-Time Polymerase Chain Reaction ; Sample Size ; Seasons ; Young Adult ; }, abstract = {BACKGROUND: Gut microbiota composition is known to depend on environmental (diet, day length, infections, xenobiotic exposure) and lifestyle (alcohol/drug intake, physical activity) factors. All these factors fluctuate seasonally, especially in areas with highly variable climatic conditions between seasons. Seasonal microbiota changes were reported in several previous studies. The purpose of our study was to investigate whether there is a seasonal variability in the gut microbiota composition in Ukrainian population. In contrast to previous studies performed on small-size samples using a longitudinal design, we used cross-sectional design with a large sample size (n = 769). Determination of microbial composition at the level of major microbial phyla was performed by qRT-PCR.<br><br>RESULTS: The relative abundance of major taxonomic groups of gut microbiota was found to be affected by month of sampling. Actinobacteria were more abundant and Bacteroidetes were less abundant in summer-derived samples compared to those obtained during other seasons, whereas Firmicutes content was seasonally independent. The Firmicutes to Bacteroidetes (F/B) ratio was significantly higher in summer-derived samples than in winter-derived ones. Odds to have F/B&#x2009;>&#x2009;1 were 3.3 times higher in summer samples and 1.9 times higher in autumn samples than in winter ones; neither age, nor sex were significant confounding factors.<br><br>CONCLUSIONS: Seasonality of sampling could influence results of human microbiome research, thereby potentially biasing estimates. This factor must be taken into consideration in further microbiome research.}, }
@article {pmid32305861, year = {2020}, author = {Ma, ZS}, title = {Testing the Anna Karenina Principle in Human Microbiome-Associated Diseases.}, journal = {iScience}, volume = {23}, number = {4}, pages = {101007}, pmid = {32305861}, issn = {2589-0042}, abstract = {The AKP (Anna Karenina principle), which refers to observations inspired by the opening line of Leo Tolstoy's Anna Karenina, "all happy families are all alike; each unhappy family is unhappy in its own way," predicts that all "healthy" microbiomes are alike and each disease-associated microbiome is "sick" in its own way in human microbiome-associated diseases (MADs). The AKP hypothesis predicts the rise of heterogeneity/stochasticity in human microbiomes associated with dysbiosis due to MADs. We used the beta-diversity in Hill numbers and stochasticity analysis to detect AKP and anti-AKP effects. We tested the AKP with 27 human MAD studies and discovered that the AKP, anti-AKP, and non-AKP effects were exhibited in approximately 50%, 25%, and 25% of the MAD cases, respectively. Mechanistically, AKP effects are primarily influenced by highly dominant microbial species and less influenced by rare species. In contrast, all species appear to play equal roles in influencing anti-AKP effects.}, }
@article {pmid32298967, year = {2020}, author = {Otto, M}, title = {Staphylococci in the human microbiome: the role of host and interbacterial interactions.}, journal = {Current opinion in microbiology}, volume = {53}, number = {}, pages = {71-77}, doi = {10.1016/j.mib.2020.03.003}, pmid = {32298967}, issn = {1879-0364}, support = {ZIA AI000904/ImNIH/Intramural NIH HHS/United States ; }, mesh = {*Host-Pathogen Interactions ; Humans ; *Microbiota ; Staphylococcal Infections/*microbiology ; Staphylococcus aureus/genetics/*physiology ; }, abstract = {Staphylococci are common commensals on human epithelial surfaces. Some species, most notably Staphylococcus aureus, have considerable pathogenic potential and can cause severe and sometimes fatal infections. Despite the long-known fact that staphylococcal infection arises from colonizing isolates, research on staphylococcal colonization has been limited, in particular regarding interactions with the colonizing microbiota. However, several recent studies are beginning to decipher such interactions, which range from bacteriocin-based or signaling interference-mediated inhibitory interactions to cooperation with host defenses to outcompete co-colonizers. This review will give an outline of recent research on the mechanistic underpinnings of staphylococcal interference with other members of the colonizing microbiota, some of which suggest new avenues for the development of novel anti-infectives or decolonization strategies.}, }
@article {pmid32298612, year = {2020}, author = {Ligthart, K and Belzer, C and de Vos, WM and Tytgat, HLP}, title = {Bridging Bacteria and the Gut: Functional Aspects of Type IV Pili.}, journal = {Trends in microbiology}, volume = {28}, number = {5}, pages = {340-348}, doi = {10.1016/j.tim.2020.02.003}, pmid = {32298612}, issn = {1878-4380}, mesh = {Bacteria/*metabolism ; Bacterial Adhesion/physiology ; *Bacterial Physiological Phenomena ; Biofilms/growth &amp; development ; Fimbriae Proteins/*metabolism ; Fimbriae, Bacterial/*metabolism ; Gastrointestinal Microbiome/*physiology ; Humans ; Locomotion/physiology ; }, abstract = {Cell-surface-located proteinaceous appendages, such as flagella and fimbriae or pili, are ubiquitous in bacterial communities. Here, we focus on conserved type IV pili (T4P) produced by bacteria in the intestinal tract, one of the most densely populated human ecosystems. Computational analysis revealed that approximately 30% of known intestinal bacteria are predicted to produce T4P. To rationalize how T4P allow intestinal bacteria to interact with their environment, other microbiota members, and host cells, we review their established role in gut commensals and pathogens with respect to adherence, motility, and biofilm formation, as well as protein secretion and DNA uptake. This work indicates that T4P are widely spread among the known members of the intestinal microbiota and that their contribution to human health might be underestimated.}, }
@article {pmid32294988, year = {2020}, author = {Tomaiuolo, R and Veneruso, I and Cariati, F and D'Argenio, V}, title = {Microbiota and Human Reproduction: The Case of Male Infertility.}, journal = {High-throughput}, volume = {9}, number = {2}, pages = {}, pmid = {32294988}, issn = {2571-5135}, support = {855720//H2020 Innovation In SMEs/ ; year 2016//EIT Health/ ; }, abstract = {The increasing interest in metagenomics is enhancing our knowledge regarding the composition and role of the microbiota in human physiology and pathology. Indeed, microbes have been reported to play a role in several diseases, including infertility. In particular, the male seminal microbiota has been suggested as an important factor able to influence couple's health and pregnancy outcomes, as well as offspring health. Nevertheless, few studies have been carried out to date to deeper investigate semen microbiome origins and functions, and its correlations with the partner's reproductive tract microbiome. Here, we report the state of the art regarding the male reproductive system microbiome and its alterations in infertility.}, }
@article {pmid32291445, year = {2020}, author = {Wu, K and Yuan, Y and Yu, H and Dai, X and Wang, S and Sun, Z and Wang, F and Fei, H and Lin, Q and Jiang, H and Chen, T}, title = {The gut microbial metabolite trimethylamine N-oxide aggravates GVHD by inducing M1 macrophage polarization in mice.}, journal = {Blood}, volume = {136}, number = {4}, pages = {501-515}, pmid = {32291445}, issn = {1528-0020}, mesh = {Animals ; Choline/*adverse effects/pharmacology ; Cytokines/genetics/immunology/metabolism ; Dietary Fats/*adverse effects/pharmacology ; *Gastrointestinal Microbiome ; *Graft vs Host Disease/genetics/immunology/metabolism/microbiology ; Inflammasomes/genetics/immunology/metabolism ; *Macrophages/immunology/metabolism/pathology ; *Methylamines/immunology/metabolism ; Mice ; Mice, Inbred BALB C ; Mice, Knockout ; *T-Lymphocytes, Helper-Inducer/immunology/metabolism/pathology ; }, abstract = {The diversity of the human microbiome heralds the difference of the impact that gut microbial metabolites exert on allogenic graft-versus-host (GVH) disease (GVHD), even though short-chain fatty acids and indole were demonstrated to reduce its severity. In this study, we dissected the role of choline-metabolized trimethylamine N-oxide (TMAO) in the GVHD process. Either TMAO or a high-choline diet enhanced the allogenic GVH reaction, whereas the analog of choline, 3,3-dimethyl-1-butanol reversed TMAO-induced GVHD severity. Interestingly, TMAO-induced alloreactive T-cell proliferation and differentiation into T-helper (Th) subtypes was seen in GVHD mice but not in in vitro cultures. We thus investigated the role of macrophage polarization, which was absent from the in vitro culture system. F4/80+CD11b+CD16/32+ M1 macrophage and signature genes, IL-1β, IL-6, TNF-α, CXCL9, and CXCL10, were increased in TMAO-induced GVHD tissues and in TMAO-cultured bone marrow-derived macrophages (BMDMs). Inhibition of the NLRP3 inflammasome reversed TMAO-stimulated M1 features, indicating that NLRP3 is the key proteolytic activator involved in the macrophage's response to TMAO stimulation. Consistently, mitochondrial reactive oxygen species and enhanced NF-κB nuclear relocalization were investigated in TMAO-stimulated BMDMs. In vivo depletion of NLRP3 in GVHD recipients not only blocked M1 polarization but also reversed GVHD severity in the presence of TMAO treatment. In conclusion, our data revealed that TMAO-induced GVHD progression resulted from Th1 and Th17 differentiation, which is mediated by the polarized M1 macrophage requiring NLRP3 inflammasome activation. It provides the link among the host choline diet, microbial metabolites, and GVH reaction, shedding light on alleviating GVHD by controlling choline intake.}, }
@article {pmid32277534, year = {2020}, author = {Meng, X and Zhang, G and Cao, H and Yu, D and Fang, X and de Vos, WM and Wu, H}, title = {Gut dysbacteriosis and intestinal disease: mechanism and treatment.}, journal = {Journal of applied microbiology}, volume = {129}, number = {4}, pages = {787-805}, pmid = {32277534}, issn = {1365-2672}, support = {17SDG33410868/AHA/American Heart Association-American Stroke Association/United States ; }, mesh = {Anti-Bacterial Agents/therapeutic use ; Dysbiosis/*microbiology/*therapy ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; Intestinal Diseases/*microbiology/therapy ; Prebiotics ; Probiotics/therapeutic use ; }, abstract = {The gut microbiome functions like an endocrine organ, generating bioactive metabolites, enzymes or small molecules that can impact host physiology. Gut dysbacteriosis is associated with many intestinal diseases including (but not limited to) inflammatory bowel disease, primary sclerosing cholangitis-IBD, irritable bowel syndrome, chronic constipation, osmotic diarrhoea and colorectal cancer. The potential pathogenic mechanism of gut dysbacteriosis associated with intestinal diseases includes the alteration of composition of gut microbiota as well as the gut microbiota-derived signalling molecules. The many correlations between the latter and the susceptibility for intestinal diseases has placed a spotlight on the gut microbiome as a potential novel target for therapeutics. Currently, faecal microbial transplantation, dietary interventions, use of probiotics, prebiotics and drugs are the major therapeutic tools utilized to impact dysbacteriosis and associated intestinal diseases. In this review, we systematically summarized the role of intestinal microbiome in the occurrence and development of intestinal diseases. The potential mechanism of the complex interplay between gut dysbacteriosis and intestinal diseases, and the treatment methods are also highlighted.}, }
@article {pmid32269511, year = {2020}, author = {Elmassry, MM and Piechulla, B}, title = {Volatilomes of Bacterial Infections in Humans.}, journal = {Frontiers in neuroscience}, volume = {14}, number = {}, pages = {257}, pmid = {32269511}, issn = {1662-4548}, abstract = {Sense of smell in humans has the capacity to detect certain volatiles from bacterial infections. Our olfactory senses were used in ancient medicine to diagnose diseases in patients. As humans are considered holobionts, each person's unique odor consists of volatile organic compounds (VOCs, volatilome) produced not only by the humans themselves but also by their beneficial and pathogenic micro-habitants. In the past decade it has been well documented that microorganisms (fungi and bacteria) are able to emit a broad range of olfactory active VOCs [summarized in the mVOC database (http://bioinformatics.charite.de/mvoc/)]. During microbial infection, the equilibrium between the human and its microbiome is altered, followed by a change in the volatilome. For several decades, physicians have been trying to utilize these changes in smell composition to develop fast and efficient diagnostic tools, particularly because volatiles detection is non-invasive and non-destructive, which would be a breakthrough in many therapies. Within this review, we discuss bacterial infections including gastrointestinal, respiratory or lung, and blood infections, focusing on the pathogens and their known corresponding volatile biomarkers. Furthermore, we cover the potential role of the human microbiota and their volatilome in certain diseases such as neurodegenerative diseases. We also report on discrete mVOCs that affect humans.}, }
@article {pmid32266088, year = {2020}, author = {Xu, J and Peng, JJ and Yang, W and Fu, K and Zhang, Y}, title = {Vaginal microbiomes and ovarian cancer: a review.}, journal = {American journal of cancer research}, volume = {10}, number = {3}, pages = {743-756}, pmid = {32266088}, issn = {2156-6976}, abstract = {The human microbiome, often termed as "the forgotten organ", is an aggregation of microorganisms and their genomes that forms a mutualistic complex with the host. Recent research has shown the symbiotic merits of a microbiome ecosystem and its crucial role in the hosts' physiological functions. Disruption of this symbiotic relationship is prone to cause a broad spectrum of ailments, including cancer. The compositional and environmental factors that tip the scales from beneficial co-existence to the development of malignancy is actively investigated. Herein we review the latest research in knowledge regarding the association between the vaginal microbiomes and oncogenesis, with a particular focus on ovarian carcinoma.}, }
@article {pmid32257965, year = {2020}, author = {Fernández de Ullivarri, M and Arbulu, S and Garcia-Gutierrez, E and Cotter, PD}, title = {Antifungal Peptides as Therapeutic Agents.}, journal = {Frontiers in cellular and infection microbiology}, volume = {10}, number = {}, pages = {105}, pmid = {32257965}, issn = {2235-2988}, mesh = {Antifungal Agents/pharmacology/therapeutic use ; Fungi ; Humans ; *Mycoses/drug therapy ; Peptides ; *Pharmaceutical Preparations ; }, abstract = {Fungi have been used since ancient times in food and beverage-making processes and, more recently, have been harnessed for the production of antibiotics and in processes of relevance to the bioeconomy. Moreover, they are starting to gain attention as a key component of the human microbiome. However, fungi are also responsible for human infections. The incidence of community-acquired and nosocomial fungal infections has increased considerably in recent decades. Antibiotic resistance development, the increasing number of immunodeficiency- and/or immunosuppression-related diseases and limited therapeutic options available are triggering the search for novel alternatives. These new antifungals should be less toxic for the host, with targeted or broader antimicrobial spectra (for diseases of known and unknown etiology, respectively) and modes of actions that limit the potential for the emergence of resistance among pathogenic fungi. Given these criteria, antimicrobial peptides with antifungal properties, i.e., antifungal peptides (AFPs), have emerged as powerful candidates due to their efficacy and high selectivity. In this review, we provide an overview of the bioactivity and classification of AFPs (natural and synthetic) as well as their mode of action and advantages over current antifungal drugs. Additionally, natural, heterologous and synthetic production of AFPs with a view to greater levels of exploitation is discussed. Finally, we evaluate the current and potential applications of these peptides, along with the future challenges relating to antifungal treatments.}, }
@article {pmid32255860, year = {2020}, author = {Yu, B and Yu, B and Yu, L}, title = {Commentary: Reconciling Hygiene and Cleanliness: A New Perspective from Human Microbiome.}, journal = {Indian journal of microbiology}, volume = {60}, number = {2}, pages = {259-261}, pmid = {32255860}, issn = {0046-8991}, abstract = {Human beings have co-evolved with the microorganisms in our environment for millions of years, and have developed into a symbiosis in a mutually beneficial/defensive way. Human beings have significant multifaceted relationships with the diverse microbial community. Apart from the important protective role of microbial community exposure in development of early immunity, millions of inimitable bacterial genes of the diverse microbial community are the indispensable source of essential nutrients like essential amino acids and essential fatty acids for human body. The essential nutrition from microbiome is harvested through xenophagy. As an immune effector, xenophagy will capture any microorganisms that touch the epithelial cells of our gastrointestinal tract, degrade them and turn them into nutrients for the use of our body.}, }
@article {pmid32247371, year = {2020}, author = {Keshavarzian, A and Engen, P and Bonvegna, S and Cilia, R}, title = {The gut microbiome in Parkinson's disease: A culprit or a bystander?.}, journal = {Progress in brain research}, volume = {252}, number = {}, pages = {357-450}, doi = {10.1016/bs.pbr.2020.01.004}, pmid = {32247371}, issn = {1875-7855}, mesh = {Animals ; Dopamine Agents/*pharmacology ; *Dysbiosis/immunology/metabolism/microbiology ; *Gastrointestinal Microbiome/immunology ; Humans ; *Inflammation/immunology/metabolism/microbiology ; *Life Style ; *Parkinson Disease/drug therapy/immunology/metabolism/microbiology ; *alpha-Synuclein/metabolism ; }, abstract = {In recent years, large-scale metagenomics projects such as the Human Microbiome Project placed the gut microbiota under the spotlight of research on its role in health and in the pathogenesis several diseases, as it can be a target for novel therapeutical approaches. The emerging concept of a microbiota modulation of the gut-brain axis in the pathogenesis of neurodegenerative disorders has been explored in several studies in animal models, as well as in human subjects. Particularly, research on changes in the composition of gut microbiota as a potential trigger for alpha-synuclein (α-syn) pathology in Parkinson's disease (PD) has gained increasing interest. In the present review, we first provide the basis to the understanding of the role of gut microbiota in healthy subjects and the molecular basis of the gut-brain interaction, focusing on metabolic and neuroinflammatory factors that could trigger the alpha-synuclein conformational changes and aggregation. Then, we critically explored preclinical and clinical studies reporting on the changes in gut microbiota in PD, as compared to healthy subjects. Furthermore, we examined the relationship between the gut microbiota and PD clinical features, discussing data consistently reported across studies, as well as the potential sources of inconsistencies. As a further step toward understanding the effects of gut microbiota on PD, we discussed the relationship between dysbiosis and response to dopamine replacement therapy, focusing on Levodopa metabolism. We conclude that further studies are needed to determine whether the gut microbiota changes observed so far in PD patients is the cause or, instead, it is merely a consequence of lifestyle changes associated with the disease. Regardless, studies so far strongly suggest that changes in microbiota appears to be impactful in pathogenesis of neuroinflammation. Thus, dysbiotic microbiota in PD could influence the disease course and response to medication, especially Levodopa. Future research will assess the impact of microbiota-directed therapeutic intervention in PD patients.}, }
@article {pmid32246318, year = {2020}, author = {Chen, B and Wang, Z and Wang, J and Su, X and Yang, J and Zhang, Q and Zhang, L}, title = {The oral microbiome profile and biomarker in Chinese type 2 diabetes mellitus patients.}, journal = {Endocrine}, volume = {68}, number = {3}, pages = {564-572}, pmid = {32246318}, issn = {1559-0100}, support = {31471202//National Natural Science Foundation of China/International ; 2016YYSP009//Shandong Provincial Key Research and Development Program/International ; }, mesh = {Adult ; Biomarkers ; China ; *Dental Caries ; *Diabetes Mellitus, Type 2 ; Humans ; *Microbiota ; RNA, Ribosomal, 16S/genetics ; }, abstract = {PURPOSE: Oral microbiota maintains a dynamic ecological balance with the host. However, a disruption in this balance can lead to oral diseases such as dental caries and periodontitis. Several studies suggest differences in microbial composition in the oral cavity between patients with T2DM and nondiabetic patients. However, there is inadequate oral microbiome-related data from Chinese patients with T2DM, and the difference in microbiome profile between Chinese patients with T2DM and other ethnicities needs to be investigated further.<br><br>METHOD: Oral swab samples were collected from 280 adult patients with T2DM and 162 healthy controls. Illumina sequencing was performed on oral samples targeting V1-V2 region of 16S rRNA gene and sequence analysis was carried in the QIIME.<br><br>RESULTS: Patients with T2DM and healthy cohorts exhibited distinct oral microbial clusters based on principal coordinate analysis (PCoA). The Firmicutes/Bacteroidetes ratio increased in T2DM and T2DM patients presented significantly higher numbers of Neisseria, Streptococcus, Haemophilus, and Pseudomonas genera, and lower numbers of Acinetobacteria compared with healthy controls. When compared with the available published data of oral and gut microbiome associated with T2DM patients, we found the ratio of Firmicutes/Bacteroidetes and the abundance of Haemophilus could be a specific microbial biomarker in Chinese patients with T2DM.<br><br>CONCLUSIONS: Our study revealed a significant difference in the oral microbiota between T2DM patients and healthy individuals. We identified 25 taxa, including 6 genera, with significant difference in abundance between T2DM and healthy controls.}, }
@article {pmid32246263, year = {2020}, author = {Swann, JR and Rajilic-Stojanovic, M and Salonen, A and Sakwinska, O and Gill, C and Meynier, A and Fança-Berthon, P and Schelkle, B and Segata, N and Shortt, C and Tuohy, K and Hasselwander, O}, title = {Considerations for the design and conduct of human gut microbiota intervention studies relating to foods.}, journal = {European journal of nutrition}, volume = {59}, number = {8}, pages = {3347-3368}, pmid = {32246263}, issn = {1436-6215}, mesh = {Food ; *Gastrointestinal Microbiome ; Gastrointestinal Tract ; Humans ; *Microbiota ; Prebiotics ; *Probiotics ; }, abstract = {With the growing appreciation for the influence of the intestinal microbiota on human health, there is increasing motivation to design and refine interventions to promote favorable shifts in the microbiota and their interactions with the host. Technological advances have improved our understanding and ability to measure this indigenous population and the impact of such interventions. However, the rapid growth and evolution of the field, as well as the diversity of methods used, parameters measured and populations studied, make it difficult to interpret the significance of the findings and translate their outcomes to the wider population. This can prevent comparisons across studies and hinder the drawing of appropriate conclusions. This review outlines considerations to facilitate the design, implementation and interpretation of human gut microbiota intervention studies relating to foods based upon our current understanding of the intestinal microbiota, its functionality and interactions with the human host. This includes parameters associated with study design, eligibility criteria, statistical considerations, characterization of products and the measurement of compliance. Methodologies and markers to assess compositional and functional changes in the microbiota, following interventions are discussed in addition to approaches to assess changes in microbiota-host interactions and host responses. Last, EU legislative aspects in relation to foods and health claims are presented. While it is appreciated that the field of gastrointestinal microbiology is rapidly evolving, such guidance will assist in the design and interpretation of human gut microbiota interventional studies relating to foods.}, }
@article {pmid32243703, year = {2020}, author = {Adams, LA and Wang, Z and Liddle, C and Melton, PE and Ariff, A and Chandraratna, H and Tan, J and Ching, H and Coulter, S and de Boer, B and Christophersen, CT and O'Sullivan, TA and Morrison, M and Jeffrey, GP}, title = {Bile acids associate with specific gut microbiota, low-level alcohol consumption and liver fibrosis in patients with non-alcoholic fatty liver disease.}, journal = {Liver international : official journal of the International Association for the Study of the Liver}, volume = {40}, number = {6}, pages = {1356-1365}, doi = {10.1111/liv.14453}, pmid = {32243703}, issn = {1478-3231}, mesh = {Adult ; Alcohol Drinking/adverse effects ; Bile Acids and Salts ; *Gastrointestinal Microbiome ; Humans ; Liver ; Liver Cirrhosis ; *Non-alcoholic Fatty Liver Disease ; RNA, Ribosomal, 16S/genetics ; }, abstract = {BACKGROUND: Bile acids (BAs) are synthesized by the liver and modified by gut bacteria, and may play an intermediary role between the gut microbiome and liver in promoting fibrosis in non-alcoholic fatty liver disease (NAFLD). We investigated the associations between serum and faecal BAs, gut microbiome and fibrosis in patients with and without NAFLD and examined the impact of diet and alcohol consumption on these relationships.<br><br>METHODS: Adult patients (n&#xa0;=&#xa0;122) underwent liver biopsy and BAs characterization by high-performance liquid chromatography/mass spectrometry. Gut microbiome composition was analysed using next-generation 16S rRNA sequencing. Diet and alcohol intake were determined by 3-day food diary.<br><br>RESULTS: Serum and faecal BA concentrations increased progressively among non-NAFLD controls (n&#xa0;=&#xa0;55), NAFLD patients with no/mild fibrosis (F0-2, n&#xa0;=&#xa0;58) and NAFLD with advanced fibrosis (F3/4, n&#xa0;=&#xa0;9). Progressive increases in serum BAs were driven by primary conjugated BAs including glycocholic acid [GCA] and secondary conjugated BAs. In contrast, faecal BA increase was driven by secondary unconjugated BAs (predominately deoxycholic acid [DCA]). Serum GCA levels and faecal DCA levels correlated with the abundance of Bacteroidaceae and Lachnospiraceae, and stool secondary BAs with an unclassifiable family of the order Bacteroidales (Bacteroidales;other). These bacterial taxa were also associated with advanced fibrosis. Modest alcohol consumption was positively correlated with faecal DCA levels and relative abundance of Lachnospiracaea and Bacteroidales;other.<br><br>CONCLUSIONS: Higher serum and faecal BA levels are associated with advanced fibrosis in NAFLD. Specific gut bacteria link alterations in BA profiles and advanced fibrosis, and may be influenced by low-level alcohol consumption.}, }
@article {pmid32240601, year = {2020}, author = {Yan, Y and Drew, DA and Markowitz, A and Lloyd-Price, J and Abu-Ali, G and Nguyen, LH and Tran, C and Chung, DC and Gilpin, KK and Meixell, D and Parziale, M and Schuck, M and Patel, Z and Richter, JM and Kelsey, PB and Garrett, WS and Chan, AT and Stadler, ZK and Huttenhower, C}, title = {Structure of the Mucosal and Stool Microbiome in Lynch Syndrome.}, journal = {Cell host &amp; microbe}, volume = {27}, number = {4}, pages = {585-600.e4}, pmid = {32240601}, issn = {1934-6069}, support = {27140/CRUK_/Cancer Research UK/United Kingdom ; P30 DK043351/DK/NIDDK NIH HHS/United States ; R01 CA202704/CA/NCI NIH HHS/United States ; L30 CA209764/CA/NCI NIH HHS/United States ; P30 CA008748/CA/NCI NIH HHS/United States ; R01 CA154426/CA/NCI NIH HHS/United States ; T32 CA009001/CA/NCI NIH HHS/United States ; K01 DK120742/DK/NIDDK NIH HHS/United States ; }, mesh = {Adenoma/microbiology ; Adult ; Aged ; Aged, 80 and over ; Colectomy/adverse effects ; Colonic Neoplasms/diagnosis/*microbiology/pathology ; Colorectal Neoplasms, Hereditary Nonpolyposis/diagnosis/*microbiology/pathology ; Feces/microbiology ; Female ; Gastrointestinal Microbiome/*genetics ; Humans ; Male ; Metagenomics ; Middle Aged ; Prospective Studies ; RNA, Ribosomal, 16S/genetics ; Transcriptome ; Tumor Microenvironment ; }, abstract = {The gut microbiota has been associated with colorectal cancer (CRC), but causal alterations preceding CRC have not been elucidated. To prospectively assess microbiome changes prior to colorectal neoplasia, we investigated samples from 100 Lynch syndrome patients using 16S rRNA gene sequencing of colon biopsies, coupled with metagenomic and metatranscriptomic sequencing of feces. Colectomy and CRC history represented the largest effects on microbiome profiles. A subset of Clostridiaceae were depleted in stool corresponding with baseline adenomas, while Desulfovibrio was enriched both in stool and in mucosal biopsies. A classifier leveraging stool metatranscriptomes resulted in modest power to predict interval development of preneoplastic colonic adenoma. Predictive transcripts corresponded with a shift in flagellin contributors and oxidative metabolic microenvironment, potentially factors in local CRC pathogenesis. This suggests that the effectiveness of prospective microbiome monitoring for adenomas may be limited but supports the potential causality of these consistent, early microbial changes in colonic neoplasia.}, }
@article {pmid32239808, year = {2020}, author = {Kim, MH and Choi, JH}, title = {An Update on Sepsis Biomarkers.}, journal = {Infection &amp; chemotherapy}, volume = {52}, number = {1}, pages = {1-18}, pmid = {32239808}, issn = {2093-2340}, abstract = {Sepsis is a dysregulated systemic reaction to a common infection, that can cause life-threatening organ dysfunction. Over the last decade, the mortality rate of patients with sepsis has decreased as long as patients are treated according to the recommendations of the Surviving Sepsis Campaign, but is still unacceptably high. Patients at risk of sepsis should therefore be identified prior to the onset of organ dysfunction and this requires a rapid diagnosis and a prompt initiation of treatment. Unfortunately, there is no gold standard for the diagnosis of sepsis and traditional standard culture methods are time-consuming. Recently, in order to overcome these limitations, biomarkers which could help in predicting the diagnosis and prognosis of sepsis, as well as being useful for monitoring the response to treatments, have been identified. In addition, recent advances have led to the development of newly identified classes of biomarkers such as microRNAs, long-non-coding RNAs, and the human microbiome. This review focuses on the latest information on biomarkers that can be used to predict the diagnosis and prognosis of sepsis.}, }
@article {pmid32239603, year = {2020}, author = {Bruessow, F and Brüssow, H}, title = {Our extended genotype-An argument for the study of domesticated microbes.}, journal = {Environmental microbiology}, volume = {22}, number = {5}, pages = {1669-1674}, doi = {10.1111/1462-2920.15001}, pmid = {32239603}, issn = {1462-2920}, mesh = {Animals ; Bacteria/*classification/*genetics ; Fermentation ; Fermented Foods/*microbiology ; Food Microbiology/*methods ; Genotype ; Humans ; Microbiota/genetics ; }, abstract = {We interpret the domesticated organisms-plants, animals, and the domesticated microbes used for food fermentation-as an extended genotype of humans due to their close relationship with our species. We propose to analyse the role of microbes in traditionally fermented food with the approaches used in the human microbiome project, and we expect to find associations with ethnic groups, explaining part of human (culinary) culture.}, }
@article {pmid32236123, year = {2020}, author = {Stennett, CA and Dyer, TV and He, X and Robinson, CK and Ravel, J and Ghanem, KG and Brotman, RM}, title = {A cross-sectional pilot study of birth mode and vaginal microbiota in reproductive-age women.}, journal = {PloS one}, volume = {15}, number = {4}, pages = {e0228574}, pmid = {32236123}, issn = {1932-6203}, support = {R25 GM055036/GM/NIGMS NIH HHS/United States ; R01 AI119012/AI/NIAID NIH HHS/United States ; T32 AG000262/AG/NIA NIH HHS/United States ; U01 AI070921/AI/NIAID NIH HHS/United States ; R01 AI089878/AI/NIAID NIH HHS/United States ; }, mesh = {Adolescent ; Adult ; Cesarean Section ; Cross-Sectional Studies ; *Delivery, Obstetric ; Female ; Humans ; Lactobacillus/isolation &amp; purification ; *Microbiota ; *Parturition ; Pilot Projects ; Pregnancy ; United States ; Vagina/*microbiology ; Vaginosis, Bacterial/epidemiology ; Young Adult ; }, abstract = {Recent studies suggest that birth mode (Cesarean section [C-section] or vaginal delivery) is an important event in the initial colonization of the human microbiome and may be associated with long-term health outcomes. We sought to determine the association between a woman's birth mode and her vaginal microbiota in adulthood. We re-contacted 144 adult women from two U.S. studies and administered a brief survey. Vaginal microbiota was characterized on a single sample by amplicon sequencing of the V3-V4 hypervariable regions of the 16S rRNA gene and clustered into community state types (CSTs). We evaluated the association between birth mode and a CST with low relative abundance of Lactobacillus spp. ("molecular bacterial vaginosis" [Molecular-BV]) compared to Lactobacillus-dominated CSTs in logistic regression modeling which adjusted for body mass index, a confounder in this analysis. Twenty-seven women (19%) reported C-section. Overall, C-section showed a non-significant trend towards increased odds of Molecular-BV (aOR = 1.22, 95% CI: 0.45, 3.32), and Prevotella bivia was the strongest single taxa associated with C-section. However, because the two archived studies had different inclusion criteria (interaction p = 0.048), we stratified the analysis by study site. In the study with a larger sample size (n = 88), women born by C-section had 3-fold higher odds of Molecular-BV compared to vaginally-delivered women (aOR = 3.55, p = 0.06, 95% CI: 0.97-13.02). No association was found in the smaller study (n = 56, aOR = 0.19, p = 0.14, 95% CI: 0.02-1.71). This pilot cross-sectional study suggests a possible association between C-section and Molecular-BV in adulthood. However, the analysis is limited by small sample size and lack of comparability in participant age and other characteristics between the study sites. Future longitudinal studies could recruit larger samples of women, address the temporal dynamics of vaginal microbiota, and explore other confounders, including maternal factors, breastfeeding history, and socioeconomic status, which may affect the relationship between birth mode and vaginal microbiota.}, }
@article {pmid32235279, year = {2020}, author = {Lundy, SD and Vij, SC and Rezk, AH and Cohen, JA and Bajic, P and Ramasamy, R}, title = {The microbiome of the infertile male.}, journal = {Current opinion in urology}, volume = {30}, number = {3}, pages = {355-362}, pmid = {32235279}, issn = {1473-6586}, mesh = {Humans ; Infertility, Male/*microbiology ; Male ; Metagenomics ; *Microbiota ; RNA, Ribosomal, 16S ; Semen/*microbiology ; Semen Analysis ; }, abstract = {PURPOSE OF REVIEW: Contrary to historic dogma, many tissues and organs in the human body contain a resident population of bacteria, fungi, and viruses collectively known as the microbiome. The microbiome plays a role in both homeostatic symbiosis and also pathogenic dysbiosis in a wide array of diseases. Our understanding of the relationship between the microbiome and male factor infertility is in its infancy but is slowly evolving.<br><br>RECENT FINDINGS: Recent literature indicates that semen (and likely the testis) is not sterile and contains a distinct microbiome, and these changes in its composition are associated with alterations in semen quality and fertility status. Preliminary investigation indicates that manipulating the human microbiome may have implications in improving semen parameters and fertility.<br><br>SUMMARY: In this review, we describe relationships between the microbiome and the genitourinary system, discuss the prior work on the relationship among bacteriospermia, leukocytospermia and male factor infertility, and summarize the current literature utilizing 16s rRNA-based next-generation sequencing on the seminal and testicular microbiome. We explore the specific microbial taxa implicated in various aspects of spermatic dysfunction and introduce preliminary evidence for therapeutic approaches to alter the microbiome and improve fertility status.}, }
@article {pmid32231681, year = {2020}, author = {Carter, KM and Lu, M and Jiang, H and An, L}, title = {An Information-Based Approach for Mediation Analysis on High-Dimensional Metagenomic Data.}, journal = {Frontiers in genetics}, volume = {11}, number = {}, pages = {148}, pmid = {32231681}, issn = {1664-8021}, abstract = {The human microbiome plays a critical role in the development of gut-related illnesses such as inflammatory bowel disease and clinical pouchitis. A mediation model can be used to describe the interaction between host gene expression, the gut microbiome, and clinical/health situation (e.g., diseased or not, inflammation level) and may provide insights into underlying disease mechanisms. Current mediation regression methodology cannot adequately model high-dimensional exposures and mediators or mixed data types. Additionally, regression based mediation models require some assumptions for the model parameters, and the relationships are usually assumed to be linear and additive. With the microbiome being the mediators, these assumptions are violated. We propose two novel nonparametric procedures utilizing information theory to detect significant mediation effects with high-dimensional exposures and mediators and varying data types while avoiding standard regression assumptions. Compared with available methods through comprehensive simulation studies, the proposed method shows higher power and lower error. The innovative method is applied to clinical pouchitis data as well and interesting results are obtained.}, }
@article {pmid32231664, year = {2020}, author = {Al-Nasiry, S and Ambrosino, E and Schlaepfer, M and Morré, SA and Wieten, L and Voncken, JW and Spinelli, M and Mueller, M and Kramer, BW}, title = {The Interplay Between Reproductive Tract Microbiota and Immunological System in Human Reproduction.}, journal = {Frontiers in immunology}, volume = {11}, number = {}, pages = {378}, pmid = {32231664}, issn = {1664-3224}, mesh = {Dysbiosis/immunology ; Female ; Genitalia, Female/*immunology/*microbiology ; Host Microbial Interactions/*immunology ; Humans ; *Microbiota ; Pregnancy/*immunology ; Pregnancy Complications/immunology/microbiology ; }, abstract = {In the last decade, the microbiota, i.e., combined populations of microorganisms living inside and on the surface of the human body, has increasingly attracted attention of researchers in the medical field. Indeed, since the completion of the Human Microbiome Project, insight and interest in the role of microbiota in health and disease, also through study of its combined genomes, the microbiome, has been steadily expanding. One less explored field of microbiome research has been the female reproductive tract. Research mainly from the past decade suggests that microbial communities residing in the reproductive tract represent a large proportion of the female microbial network and appear to be involved in reproductive failure and pregnancy complications. Microbiome research is facing technological and methodological challenges, as detection techniques and analysis methods are far from being standardized. A further hurdle is understanding the complex host-microbiota interaction and the confounding effect of a multitude of constitutional and environmental factors. A key regulator of this interaction is the maternal immune system that, during the peri-conceptional stage and even more so during pregnancy, undergoes considerable modulation. This review aims to summarize the current literature on reproductive tract microbiota describing the composition of microbiota in different anatomical locations (vagina, cervix, endometrium, and placenta). We also discuss putative mechanisms of interaction between such microbial communities and various aspects of the immune system, with a focus on the characteristic immunological changes during normal pregnancy. Furthermore, we discuss how abnormal microbiota composition, "dysbiosis," is linked to a spectrum of clinical disorders related to the female reproductive system and how the maternal immune system is involved. Finally, based on the data presented in this review, the future perspectives in diagnostic approaches, research directions and therapeutic opportunities are explored.}, }
@article {pmid32231240, year = {2020}, author = {Chaudhari, DS and Dhotre, DP and Agarwal, DM and Gaike, AH and Bhalerao, D and Jadhav, P and Mongad, D and Lubree, H and Sinkar, VP and Patil, UK and Salvi, S and Bavdekar, A and Juvekar, SK and Shouche, YS}, title = {Gut, oral and skin microbiome of Indian patrilineal families reveal perceptible association with age.}, journal = {Scientific reports}, volume = {10}, number = {1}, pages = {5685}, pmid = {32231240}, issn = {2045-2322}, mesh = {Adolescent ; Adult ; *Age Factors ; Aged ; Aged, 80 and over ; Bacteria/genetics ; Child ; Child, Preschool ; Family ; Feces/microbiology ; Female ; Gastrointestinal Microbiome/genetics ; Humans ; India/epidemiology ; Male ; Metagenome/genetics ; Metagenomics/methods ; Microbiota/*genetics ; Middle Aged ; Mouth/microbiology ; RNA, Ribosomal, 16S/genetics ; Skin/microbiology ; }, abstract = {The human microbiome plays a key role in maintaining host homeostasis and is influenced by age, geography, diet, and other factors. Traditionally, India has an established convention of extended family arrangements wherein three or more generations, bound by genetic relatedness, stay in the same household. In the present study, we have utilized this unique family arrangement to understand the association of age with the microbiome. We characterized stool, oral and skin microbiome of 54 healthy individuals from six joint families by 16S rRNA gene-based metagenomics. In total, 69 (1.03%), 293 (2.68%) and 190 (8.66%) differentially abundant OTUs were detected across three generations in the gut, skin and oral microbiome, respectively. Age-associated changes in the gut and oral microbiome of patrilineal families showed positive correlations in the abundance of phyla Proteobacteria and Fusobacteria, respectively. Genera Treponema and Fusobacterium showed a positive correlation with age while Granulicatella and Streptococcus showed a negative correlation with age in the oral microbiome. Members of genus Prevotella illustrated high abundance and prevalence as a core OTUs in the gut and oral microbiome. In conclusion, this study highlights that precise and perceptible association of age with microbiome can be drawn when other causal factors are kept constant.}, }
@article {pmid32230951, year = {2020}, author = {Hiippala, K and Kainulainen, V and Suutarinen, M and Heini, T and Bowers, JR and Jasso-Selles, D and Lemmer, D and Valentine, M and Barnes, R and Engelthaler, DM and Satokari, R}, title = {Isolation of Anti-Inflammatory and Epithelium Reinforcing Bacteroides and Parabacteroides Spp. from A Healthy Fecal Donor.}, journal = {Nutrients}, volume = {12}, number = {4}, pages = {}, pmid = {32230951}, issn = {2072-6643}, support = {304490//Academy of Finland/ ; 323156//Academy of Finland/ ; 285632//Academy of Finland/ ; Reetta Satokari//Sigrid Jus&#xe9;liuksen S&#xe4;&#xe4;ti&#xf6;/ ; }, mesh = {Adult ; Anti-Inflammatory Agents/*metabolism ; *Bacteroides/classification/immunology/isolation &amp; purification/metabolism ; Bacteroidetes/classification/immunology/isolation &amp; purification/metabolism ; Caco-2 Cells ; Feces/microbiology ; Female ; Gastrointestinal Microbiome/*immunology ; High-Throughput Screening Assays ; Homeostasis/immunology ; Humans ; Interleukin-8/analysis/metabolism ; Lipopolysaccharides/metabolism ; Probiotics ; }, abstract = {Altered intestinal microbiota is associated with systemic and intestinal diseases, such as inflammatory bowel disease (IBD). Dysbiotic microbiota with enhanced proinflammatory capacity is characterized by depletion of anaerobic commensals, increased proportion of facultatively anaerobic bacteria, as well as reduced diversity and stability. In this study, we developed a high-throughput in vitro screening assay to isolate intestinal commensal bacteria with anti-inflammatory capacity from a healthy fecal microbiota transplantation donor. Freshly isolated gut bacteria were screened for their capacity to attenuate Escherichia coli lipopolysaccharide (LPS)-induced interleukin 8 (IL-8) release from HT-29 cells. The screen yielded a number of Bacteroides and Parabacteroides isolates, which were identified as P. distasonis, B. caccae, B. intestinalis, B. uniformis, B. fragilis, B. vulgatus and B. ovatus using whole genome sequencing. We observed that a cell-cell contact with the epithelium was not necessary to alleviate in vitro inflammation as spent culture media from the isolates were also effective and the anti-inflammatory action did not correlate with the enterocyte adherence capacity of the isolates. The anti-inflammatory isolates also exerted enterocyte monolayer reinforcing action and lacked essential genes to synthetize hexa-acylated, proinflammatory lipid A, part of LPS. Yet, the anti-inflammatory effector molecules remain to be identified. The Bacteroides strains isolated and characterized in this study have potential to be used as so-called next-generation probiotics.}, }
@article {pmid32229436, year = {2020}, author = {Zheng, JS and Wahlqvist, ML}, title = {Regulobiosis: A regulatory and food system-sensitive role for fungal symbionts in human evolution and ecobiology.}, journal = {Asia Pacific journal of clinical nutrition}, volume = {29}, number = {1}, pages = {9-15}, doi = {10.6133/apjcn.202003_29(1).0002}, pmid = {32229436}, issn = {1440-6047}, mesh = {Diet ; Fungi/*physiology ; *Host Microbial Interactions ; Humans ; *Microbial Interactions ; Microbiota/*physiology ; Mycobiome/*physiology ; *Symbiosis ; }, abstract = {The role of microbiomes in human biology and health are being extensively investigated, yet how the fungal community or mycobiome contributes to an integral microbiome is unclear and probably underestimated. We review the roles of fungi from the perspectives of their functionality in human biology, their cross-kingdom talk with other human microbial organisms, their dependence on diet and their involvement in human health and diseases. We hypothesize that members of the fungal community may interact as necessary symbionts with members of other human microbiome communities, and play a key role in human biology, yet to be fully understood. We propose further that "regulobiosis", whereby fungi play a regulatory role in human ecobiology, is operative in humans as probably obtains in other forms of life. Fungally-dependent regulobiosis would characterise, at first, microbiomes which include, but are not limited to, bacteria, archaea, and viruses; then, their human host; and, next, provide ecological connectedness.}, }
@article {pmid32221294, year = {2020}, author = {Gilijamse, PW and Hartstra, AV and Levin, E and Wortelboer, K and Serlie, MJ and Ackermans, MT and Herrema, H and Nederveen, AJ and Imangaliyev, S and Aalvink, S and Sommer, M and Levels, H and Stroes, ESG and Groen, AK and Kemper, M and de Vos, WM and Nieuwdorp, M and Prodan, A}, title = {Treatment with Anaerobutyricum soehngenii: a pilot study of safety and dose-response effects on glucose metabolism in human subjects with metabolic syndrome.}, journal = {NPJ biofilms and microbiomes}, volume = {6}, number = {1}, pages = {16}, pmid = {32221294}, issn = {2055-5008}, mesh = {Administration, Oral ; Adult ; Aged ; Bacteria/*classification/genetics/isolation &amp; purification ; Bile Acids and Salts/metabolism ; Clostridiales/*physiology ; Dietary Supplements/adverse effects ; Dose-Response Relationship, Drug ; Feces/*microbiology ; Gastrointestinal Microbiome ; Glucose/*metabolism ; Humans ; Male ; Metabolic Syndrome/*diet therapy/metabolism ; Middle Aged ; Pilot Projects ; Sequence Analysis, DNA ; Treatment Outcome ; }, abstract = {Dysbiosis of the intestinal microbiota has been implicated in insulin resistance, although evidence regarding causality in humans is scarce. We performed a phase I/II dose-finding and safety study on the effect of oral intake of the anaerobic butyrogenic strain Anaerobutyricum soehngenii on glucose metabolism in 24 subjects with metabolic syndrome. We found that treatment with A. soehngenii was safe and observed a significant correlation between the measured fecal abundance of administered A. soehngenii and improvement in peripheral insulin sensitivity after 4 weeks of treatment. This was accompanied by an altered microbiota composition and a change in bile acid metabolism. Finally, we show that metabolic response upon administration of A. soehngenii (defined as improved insulin sensitivity 4 weeks after A. soehngenii intake) is dependent on microbiota composition at baseline. These data in humans are promising, but additional studies are needed to reproduce our findings and to investigate long-term effects, as well as other modes of delivery.}, }
@article {pmid32219339, year = {2020}, author = {Kyrgyzov, O and Prost, V and Gazut, S and Farcy, B and Brüls, T}, title = {Binning unassembled short reads based on k-mer abundance covariance using sparse coding.}, journal = {GigaScience}, volume = {9}, number = {4}, pages = {}, pmid = {32219339}, issn = {2047-217X}, mesh = {Cluster Analysis ; Genome, Bacterial/*genetics ; Humans ; Metagenome/*genetics ; Metagenomics/*methods ; *Software ; }, abstract = {BACKGROUND: Sequence-binning techniques enable the recovery of an increasing number of genomes from complex microbial metagenomes and typically require prior metagenome assembly, incurring the computational cost and drawbacks of the latter, e.g., biases against low-abundance genomes and inability to conveniently assemble multi-terabyte datasets.<br><br>RESULTS: We present here a scalable pre-assembly binning scheme (i.e., operating on unassembled short reads) enabling latent genome recovery by leveraging sparse dictionary learning and elastic-net regularization, and its use to recover hundreds of metagenome-assembled genomes, including very low-abundance genomes, from a joint analysis of microbiomes from the LifeLines DEEP population cohort (n = 1,135, >1010 reads).<br><br>CONCLUSION: We showed that sparse coding techniques can be leveraged to carry out read-level binning at large scale and that, despite lower genome reconstruction yields compared to assembly-based approaches, bin-first strategies can complement the more widely used assembly-first protocols by targeting distinct genome segregation profiles. Read enrichment levels across 6 orders of magnitude in relative abundance were observed, indicating that the method has the power to recover genomes consistently segregating at low levels.}, }
@article {pmid32214138, year = {2020}, author = {Kummen, M and Solberg, OG and Storm-Larsen, C and Holm, K and Ragnarsson, A and Trøseid, M and Vestad, B and Skårdal, R and Yndestad, A and Ueland, T and Svardal, A and Berge, RK and Seljeflot, I and Gullestad, L and Karlsen, TH and Aaberge, L and Aukrust, P and Hov, JR}, title = {Rosuvastatin alters the genetic composition of the human gut microbiome.}, journal = {Scientific reports}, volume = {10}, number = {1}, pages = {5397}, pmid = {32214138}, issn = {2045-2322}, support = {2016067//Helse S&#xf8;r-&#xf8;st RHF/International ; 240787/F20//Norges Forskningsr&#xe5;d/International ; }, mesh = {Adult ; Aged ; Feces/microbiology ; Female ; Gastrointestinal Microbiome/*drug effects/*genetics/physiology ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/pharmacology ; Microbiota/drug effects/genetics ; Middle Aged ; RNA, Ribosomal, 16S/genetics ; Rosuvastatin Calcium/metabolism/*pharmacology ; }, abstract = {The gut microbiome contributes to the variation of blood lipid levels, and secondary bile acids are associated with the effect of statins. Yet, our knowledge of how statins, one of our most common drug groups, affect the human microbiome is scarce. We aimed to characterize the effect of rosuvastatin on gut microbiome composition and inferred genetic content in stool samples from a randomized controlled trial (n = 66). No taxa were significantly altered by rosuvastatin during the study. However, rosuvastatin-treated participants showed a reduction in the collective genetic potential to transport and metabolize precursors of the pro-atherogenic metabolite trimethylamine-N-oxide (TMAO, p < 0.01), and an increase of related metabolites betaine and γ-butyrobetaine in plasma (p < 0.01). Exploratory analyses in the rosuvastatin group showed that participants with the least favorable treatment response (defined as < median change in high-density/low-density lipoprotein (HDL/LDL) ratio) showed a marked increase in TMAO-levels compared to those with a more favorable response (p < 0.05). Our data suggest that while rosuvastatin has a limited effect on gut microbiome composition, it could exert broader collective effects on the microbiome relevant to their function, providing a rationale for further studies of the influence of statins on the gut microbiome.}, }
@article {pmid32200333, year = {2020}, author = {Ben, Y and Hu, M and Zhang, X and Wu, S and Wong, MH and Wang, M and Andrews, CB and Zheng, C}, title = {Efficient detection and assessment of human exposure to trace antibiotic residues in drinking water.}, journal = {Water research}, volume = {175}, number = {}, pages = {115699}, doi = {10.1016/j.watres.2020.115699}, pmid = {32200333}, issn = {1879-2448}, mesh = {Anti-Bacterial Agents ; China ; Cities ; *Drinking Water ; Humans ; }, abstract = {Human exposure to antibiotic residues in drinking water has not been well evaluated. This study is the first attempt to simultaneously and efficiently identify and quantify 92 antibiotic residues in filtered tap water (multistage filtration at the tap) (n = 36) collected from 10 areas of a large city in southern China, 10 Chinese brands of bottled/barreled water (n = 30) and six foreign brands of bottled water (n = 18) obtained from the Chinese market. The average and median concentrations of all the detected antibiotic compounds was 182 and 92 ng/L in filtered tap water, 180 and 105 ng/L in Chinese brands of bottled/barreled water, and 666 and 146 ng/L in foreign brands of bottled water, respectively. A total of 58 antibiotics were detected in the filtered tap water, and 45 and 36 antibiotics were detected in the Chinese and foreign brands of bottled water, respectively. More types of antibiotics were detected in Chinese brands of bottled water than in the other bottled waters. In addition, Chinese waters had high roxithromycin concentrations, while the foreign brands of bottled water had high concentrations of dicloxacillin. The average and median values of the estimated overall daily intake of all the detected antibiotics were 4.3 and 2.3 ng/kg/day when only filtered tap water was drunk, 4.0 and 2.5 ng/kg/day when Chinese brands of bottled water was drunk, and 16.0 and 4.9 ng/kg/day when foreign brands of bottled water was drunk. Further study is needed to develop a more comprehensive estimation of human exposure to antibiotic residues in the environment and a more in-depth understanding of the potential hazard of ingested antibiotic residues to the human microbiome.}, }
@article {pmid32199025, year = {2020}, author = {Puhlmann, ML and de Vos, WM}, title = {Back to the Roots: Revisiting the Use of the Fiber-Rich Cichorium intybusL. Taproots.}, journal = {Advances in nutrition (Bethesda, Md.)}, volume = {11}, number = {4}, pages = {878-889}, pmid = {32199025}, issn = {2156-5376}, mesh = {*Cichorium intybus ; Dietary Fiber ; Humans ; Phytochemicals ; Plant Extracts ; Prebiotics ; }, abstract = {Fibers are increasingly recognized as an indispensable part of our diet and vital for maintaining health. Notably, complex mixtures of fibers have been found to improve metabolic health. Following an analysis of the fiber content of plant-based products, we found the taproot of the chicory plant (Cichorium intybusL.) to be 1 of the vegetables with the highest fiber content, comprising nearly 90% of its dry weight. Chicory roots consist of a mixture of inulin, pectin, and (hemi-)cellulose and also contain complex phytochemicals, such as sesquiterpene lactones that have been characterized in detail. Nowaday, chicory roots are mainly applied as a source for the extraction of inulin, which is used as prebiotic fiber and food ingredient. Chicory roots, however, have long been consumed as a vegetable by humans. The whole root has been used for thousands of years for nutritional, medicinal, and other purposes, and it is still used in traditional dishes in various parts of the world. Here, we summarize the composition of chicory roots to explain their historic success in the human diet. We revisit the intake of chicory roots by humans and describe the different types of use along with their various methods of preparation. Hereby, we focus on the whole root in its complex, natural form, as well as in relation to its constituents, and discuss aspects regarding legal regulation and the safety of chicory root extracts for human consumption. Finally, we provide an overview of the current and future applications of chicory roots and their contribution to a fiber-rich diet.}, }
@article {pmid32194617, year = {2020}, author = {Jensen, CS and Norsigian, CJ and Fang, X and Nielsen, XC and Christensen, JJ and Palsson, BO and Monk, JM}, title = {Reconstruction and Validation of a Genome-Scale Metabolic Model of Streptococcus oralis (iCJ415), a Human Commensal and Opportunistic Pathogen.}, journal = {Frontiers in genetics}, volume = {11}, number = {}, pages = {116}, pmid = {32194617}, issn = {1664-8021}, abstract = {The mitis group of streptococci (MGS) is a member of the healthy human microbiome in the oral cavity and upper respiratory tract. Troublingly, some MGS are able to escape this niche and cause infective endocarditis, a severe and devastating disease. Genome-scale models have been shown to be valuable in investigating metabolism of bacteria. Here we present the first genome-scale model, iCJ415, for Streptococcus oralis SK141. We validated the model using gene essentiality and amino acid auxotrophy data from closely related species. iCJ415 has 71-76% accuracy in predicting gene essentiality and 85% accuracy in predicting amino acid auxotrophy. Further, the phenotype of S. oralis was tested using the Biolog Phenotype microarrays, giving iCJ415 a 82% accuracy in predicting carbon sources. iCJ415 can be used to explore the metabolic differences within the MGS, and to explore the complicated metabolic interactions between different species in the human oral cavity.}, }
@article {pmid32186326, year = {2020}, author = {Fragiadakis, GK and Wastyk, HC and Robinson, JL and Sonnenburg, ED and Sonnenburg, JL and Gardner, CD}, title = {Long-term dietary intervention reveals resilience of the gut microbiota despite changes in diet and weight.}, journal = {The American journal of clinical nutrition}, volume = {111}, number = {6}, pages = {1127-1136}, pmid = {32186326}, issn = {1938-3207}, support = {R01 DK091831/DK/NIDDK NIH HHS/United States ; R01 DK085025/DK/NIDDK NIH HHS/United States ; T32 AI007328/AI/NIAID NIH HHS/United States ; UL1 TR001085/TR/NCATS NIH HHS/United States ; UL1 TR003142/TR/NCATS NIH HHS/United States ; }, mesh = {Adult ; Bacteria/classification/genetics/isolation &amp; purification ; Diet, Carbohydrate-Restricted ; Diet, Fat-Restricted ; Diet, Reducing ; Feces ; Female ; *Gastrointestinal Microbiome ; Humans ; Longitudinal Studies ; Male ; Middle Aged ; Obesity/*diet therapy/metabolism/microbiology/physiopathology ; Weight Loss ; Young Adult ; }, abstract = {BACKGROUND: With the rising rates of obesity and associated metabolic disorders, there is a growing need for effective long-term weight-loss strategies, coupled with an understanding of how they interface with human physiology. Interest is growing in the potential role of gut microbes as they pertain to responses to different weight-loss diets; however, the ways that diet, the gut microbiota, and long-term weight loss influence one another is not well understood.<br><br>OBJECTIVES: Our primary objective was to determine if baseline microbiota composition or diversity was associated with weight-loss success. A secondary objective was to track the longitudinal associations of changes to lower-carbohydrate or lower-fat diets and concomitant weight loss with the composition and diversity of the gut microbiota.<br><br>METHODS: We used 16S ribosomal RNA gene amplicon sequencing to profile microbiota composition over a 12-mo period in 49 participants as part of a larger randomized dietary intervention study of participants consuming either a healthy low-carbohydrate or a healthy low-fat diet.<br><br>RESULTS: While baseline microbiota composition was not predictive of weight loss, each diet resulted in substantial changes in the microbiota 3-mo after the start of the intervention; some of these changes were diet specific (14 taxonomic changes specific to the healthy low-carbohydrate diet, 12 taxonomic changes specific to the healthy low-fat diet) and others tracked with weight loss (7 taxonomic changes in both diets). After these initial shifts, the microbiota returned near its original baseline state for the remainder of the intervention, despite participants maintaining their diet and weight loss for the entire study.<br><br>CONCLUSIONS: These results suggest a resilience to perturbation of the microbiota's starting profile. When considering the established contribution of obesity-associated microbiotas to weight gain in animal models, microbiota resilience may need to be overcome for long-term alterations to human physiology. This trial was registered at clinicaltrials.gov as NCT01826591.}, }
@article {pmid32180472, year = {2020}, author = {Zou, Y and Wu, L and Xu, W and Zhou, X and Ye, K and Xiong, H and Song, C and Xie, Y}, title = {Correlation between antibiotic use in childhood and subsequent inflammatory bowel disease: a systematic review and meta-analysis.}, journal = {Scandinavian journal of gastroenterology}, volume = {55}, number = {3}, pages = {301-311}, doi = {10.1080/00365521.2020.1737882}, pmid = {32180472}, issn = {1502-7708}, mesh = {Anti-Bacterial Agents/*adverse effects ; Child ; Colitis, Ulcerative/*chemically induced/epidemiology ; Crohn Disease/*chemically induced/epidemiology ; Humans ; Risk Factors ; }, abstract = {Background: Antibiotic use leads to a cascade of inflammatory reaction in the gastrointestinal tract due to its association with a temporary disruption of human microbiome.Objectives: To explore the undetermined correlation between antibiotic use in childhood and subsequent inflammatory bowel disease (IBD).Methods: PUBMED, EMBASE and Cochrane Central Register of Controlled Trials were searched to identify related articles. We extracted and pooled the (adjusted) odds ratio (OR) and (adjusted) risk ratio (RR).Results: This systematic review and meta-analysis included 11 studies. The pooled OR of all 11 studies was 1.5 (95% confidence interval (CI): 1.22-1.85). The pooled ORs of the subsequent Crohn's disease and ulcerative colitis after antibiotic use in childhood were 1.59 (95% CI: 1.06-2.4) and 1.22 (95% CI: 0.82-1.8). The sensitivity analysis showed no change. The meta-regression showed there was not statistical significance for the publication year, research area and research methods. Egger's test showed publication bias in the IBD studies (p = .006 < .05) but no publication bias for the CD (p = .275>.05) and UC studies (p = .537>.05).Conclusions: There was a positive association between antibiotic use in childhood and the subsequently risk of Crohn's disease in non-European countries in the west during 2010-2013. Children in the United States taking antibiotics will have a higher risk of subsequently IBD than Europe, Asia and Australia. Registration number: CRD42019147648 (PROSPERO).}, }
@article {pmid32179736, year = {2019}, author = {El-Awady, A and de Sousa Rabelo, M and Meghil, MM and Rajendran, M and Elashiry, M and Stadler, AF and Foz, AM and Susin, C and Romito, GA and Arce, RM and Cutler, CW}, title = {Polymicrobial synergy within oral biofilm promotes invasion of dendritic cells and survival of consortia members.}, journal = {NPJ biofilms and microbiomes}, volume = {5}, number = {1}, pages = {11}, pmid = {32179736}, issn = {2055-5008}, support = {R01 DE014328/DE/NIDCR NIH HHS/United States ; R01 DE029468/DE/NIDCR NIH HHS/United States ; R21 DE020916/DE/NIDCR NIH HHS/United States ; }, mesh = {Biofilms/*growth &amp; development ; Coinfection/*microbiology ; Dendritic Cells/*microbiology ; Fimbriae, Bacterial/genetics ; Fusobacterium nucleatum/genetics/physiology ; Gingiva/*microbiology ; Humans ; Inflammation ; *Microbial Consortia ; Microbiota ; Periodontitis/*microbiology ; Porphyromonas gingivalis/genetics/physiology ; RNA, Ribosomal, 16S/genetics ; Streptococcus gordonii/genetics/physiology ; }, abstract = {Years of human microbiome research have confirmed that microbes rarely live or function alone, favoring diverse communities. Yet most experimental host-pathogen studies employ single species models of infection. Here, the influence of three-species oral microbial consortium on growth, virulence, invasion and persistence in dendritic cells (DCs) was examined experimentally in human monocyte-derived dendritic cells (DCs) and in patients with periodontitis (PD). Cooperative biofilm formation by Streptococcus gordonii, Fusobacterium nucleatum and Porphyromonas gingivalis was documented in vitro using growth models and scanning electron microscopy. Analysis of growth rates by species-specific 16s rRNA probes revealed distinct, early advantages to consortium growth for S. gordonii and F. nucleatum with P. gingivalis, while P. gingivalis upregulated its short mfa1 fimbriae, leading to increased invasion of DCs. F. nucleatum was only taken up by DCs when in consortium with P. gingivalis. Mature consortium regressed DC maturation upon uptake, as determined by flow cytometry. Analysis of dental plaques of PD and healthy subjects by 16s rRNA confirmed oral colonization with consortium members, but DC hematogenous spread was limited to P. gingivalis and F. nucleatum. Expression of P. gingivalis mfa1 fimbriae was increased in dental plaques and hematogenous DCs of PD patients. P. gingivalis in the consortium correlated with an adverse clinical response in the gingiva of PD subjects. In conclusion, we have identified polymicrobial synergy in a three-species oral consortium that may have negative consequences for the host, including microbial dissemination and adverse peripheral inflammatory responses.}, }
@article {pmid32179576, year = {2020}, author = {Tuompo, R and Lääveri, T and Hannu, T and Pakkanen, SH and Kirveskari, J and Leirisalo-Repo, M and Kantele, A}, title = {Reactive arthritis and other musculoskeletal symptoms associated with acquisition of diarrhoeagenic Escherichia coli (DEC).}, journal = {Annals of the rheumatic diseases}, volume = {79}, number = {5}, pages = {605-611}, pmid = {32179576}, issn = {1468-2060}, mesh = {Academic Medical Centers ; Anti-Bacterial Agents/*therapeutic use ; Arthritis, Reactive/*epidemiology/etiology/physiopathology ; Cohort Studies ; Diarrhea/*complications/diagnosis/microbiology ; Escherichia coli/pathogenicity ; Escherichia coli Infections/*complications/diagnosis ; Female ; Finland ; Humans ; Incidence ; Logistic Models ; Male ; Middle Aged ; Multiplex Polymerase Chain Reaction/methods ; Multivariate Analysis ; Musculoskeletal Diseases/*epidemiology/etiology/physiopathology ; Prognosis ; Prohibitins ; Prospective Studies ; Risk Assessment ; Severity of Illness Index ; *Travel-Related Illness ; }, abstract = {OBJECTIVES: Using a prospective research design, we evaluated the association between acquisition of diarrhoeagenic Escherichia coli (DEC) and development of reactive arthritis (ReA) and other reactive musculoskeletal (MSK) symptoms among international travellers.<br><br>METHODS: A total of 526 study participants were asked to provide pretravel and post-travel stool samples and fill in questionnaires (pretravel, post-travel and 3-week follow-up). A multiplex quantitative PCR assay was deployed to detect five DEC comprising enteroaggregative E. coli, enteropathogenic E. coli, enterotoxigenic E. coli, enterohaemorrhagic E. coli and enteroinvasive E. coli and Salmonella, Shigella, Campylobacter, Yersinia, and Vibrio cholerae. Multivariate analysis was employed to identify factors predisposing to MSK symptoms. New post-travel MSK symptoms reported by participants with DEC were assessed by phone interviews and, if needed, clinically confirmed.<br><br>RESULTS: From among the total of 224 volunteers who returned all questionnaires and stool specimens, 38 (17.0%) reported MSK symptoms. Multivariate analysis revealed that acquisition of DEC was associated with MSK symptoms (OR 3.9; 95%&#x2009;CI 1.2 to 13.3). Of the 151 with only-DEC, four (2.6%) had ReA, two (1.3%) reactive tendinitis and three (2.0%) reactive arthralgia. ReA was mostly mild, and all patients with ReA were negative for human leucocyte antigen B27. Antibiotic treatment of travellers' diarrhoea did not prevent development of MSK symptoms.<br><br>CONCLUSION: A total of 17% of volunteers reported post-travel MSK symptoms. DEC acquisition was associated with an increased risk of developing them, yet the ReA incidence remained low and the clinical picture mild. Antibiotic treatment did not protect against development of MSK symptoms.}, }
@article {pmid32174900, year = {2020}, author = {Sarra, A and Celluzzi, A and Bruno, SP and Ricci, C and Sennato, S and Ortore, MG and Casciardi, S and Del Chierico, F and Postorino, P and Bordi, F and Masotti, A}, title = {Biophysical Characterization of Membrane Phase Transition Profiles for the Discrimination of Outer Membrane Vesicles (OMVs) From Escherichia coli Grown at Different Temperatures.}, journal = {Frontiers in microbiology}, volume = {11}, number = {}, pages = {290}, pmid = {32174900}, issn = {1664-302X}, abstract = {Dynamic Light Scattering (DLS), Small Angle X-ray Scattering (SAXS) and Transmission Electron Microscopy (TEM) are physical techniques widely employed to characterize the morphology and the structure of vesicles such as liposomes or human extracellular vesicles (exosomes). Bacterial extracellular vesicles are similar in size to human exosomes, although their function and membrane properties have not been elucidated in such detail as in the case of exosomes. Here, we applied the above cited techniques, in synergy with the thermotropic characterization of the vesicles lipid membrane using a turbidimetric technique to the study of vesicles produced by Gram-negative bacteria (Outer Membrane Vesicles, OMVs) grown at different temperatures. This study demonstrated that our combined approach is useful to discriminate vesicles of different origin or coming from bacteria cultured under different experimental conditions. We envisage that in a near future the techniques employed in our work will be further implemented to discriminate complex mixtures of bacterial vesicles, thus showing great promises for biomedical or diagnostic applications.}, }
@article {pmid32170007, year = {2020}, author = {Bhatt, AP and Pellock, SJ and Biernat, KA and Walton, WG and Wallace, BD and Creekmore, BC and Letertre, MM and Swann, JR and Wilson, ID and Roques, JR and Darr, DB and Bailey, ST and Montgomery, SA and Roach, JM and Azcarate-Peril, MA and Sartor, RB and Gharaibeh, RZ and Bultman, SJ and Redinbo, MR}, title = {Targeted inhibition of gut bacterial β-glucuronidase activity enhances anticancer drug efficacy.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {117}, number = {13}, pages = {7374-7381}, pmid = {32170007}, issn = {1091-6490}, support = {R01 GM135218/GM/NIGMS NIH HHS/United States ; P40 OD010995/OD/NIH HHS/United States ; P30 DK034987/DK/NIDDK NIH HHS/United States ; P30 CA016086/CA/NCI NIH HHS/United States ; R01 GM137286/GM/NIGMS NIH HHS/United States ; R01 CA207416/CA/NCI NIH HHS/United States ; T32 DK007737/DK/NIDDK NIH HHS/United States ; R01 CA098468/CA/NCI NIH HHS/United States ; P30 ES010126/ES/NIEHS NIH HHS/United States ; P01 DK094779/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Antineoplastic Agents, Phytogenic/pharmacology ; Bacteria/drug effects ; Disease Models, Animal ; Dysbiosis/drug therapy ; Enzyme Inhibitors/pharmacology ; Female ; Gastrointestinal Microbiome/*drug effects ; Glucuronidase/*antagonists &amp; inhibitors/*drug effects/metabolism ; Humans ; Irinotecan/pharmacology ; Mice ; Mice, Nude ; Neoplasms/drug therapy ; }, abstract = {Irinotecan treats a range of solid tumors, but its effectiveness is severely limited by gastrointestinal (GI) tract toxicity caused by gut bacterial β-glucuronidase (GUS) enzymes. Targeted bacterial GUS inhibitors have been shown to partially alleviate irinotecan-induced GI tract damage and resultant diarrhea in mice. Here, we unravel the mechanistic basis for GI protection by gut microbial GUS inhibitors using in vivo models. We use in vitro, in fimo, and in vivo models to determine whether GUS inhibition alters the anticancer efficacy of irinotecan. We demonstrate that a single dose of irinotecan increases GI bacterial GUS activity in 1 d and reduces intestinal epithelial cell proliferation in 5 d, both blocked by a single dose of a GUS inhibitor. In a tumor xenograft model, GUS inhibition prevents intestinal toxicity and maintains the antitumor efficacy of irinotecan. Remarkably, GUS inhibitor also effectively blocks the striking irinotecan-induced bloom of Enterobacteriaceae in immune-deficient mice. In a genetically engineered mouse model of cancer, GUS inhibition alleviates gut damage, improves survival, and does not alter gut microbial composition; however, by allowing dose intensification, it dramatically improves irinotecan's effectiveness, reducing tumors to a fraction of that achieved by irinotecan alone, while simultaneously promoting epithelial regeneration. These results indicate that targeted gut microbial enzyme inhibitors can improve cancer chemotherapeutic outcomes by protecting the gut epithelium from microbial dysbiosis and proliferative crypt damage.}, }
@article {pmid32169076, year = {2020}, author = {Murugesan, S and Al Ahmad, SF and Singh, P and Saadaoui, M and Kumar, M and Al Khodor, S}, title = {Profiling the Salivary microbiome of the Qatari population.}, journal = {Journal of translational medicine}, volume = {18}, number = {1}, pages = {127}, pmid = {32169076}, issn = {1479-5876}, mesh = {Adult ; Aged ; Bacteria/genetics ; Female ; High-Throughput Nucleotide Sequencing ; Humans ; Male ; *Microbiota ; RNA, Ribosomal, 16S/genetics ; Saliva ; }, abstract = {BACKGROUND: The role of the human microbiome in human health and disease has been studied in various body sites. However, compared to the gut microbiome, where most of the research focus is, the salivary microbiome still bears a vast amount of information that needs to be revealed. This study aims to characterize the salivary microbiome composition in the Qatari population, and to explore specific microbial signatures that can be associated with various lifestyles and different oral conditions.<br><br>MATERIALS AND METHODS: We characterized the salivary microbiome of 997 Qatari adults using high-throughput sequencing of the V1-V3 region of the 16S rRNA gene.<br><br>RESULTS: In this study, we have characterized the salivary microbiome of 997 Qatari participants. Our data show that Bacteroidetes, Firmicutes, Actinobacteria and Proteobacteria are the common phyla isolated from the saliva samples, with Bacteroidetes being the most predominant phylum. Bacteroidetes was also more predominant in males versus females in the study cohort, although differences in the microbial diversity were not statistically significant. We also show that, a lower diversity of the salivary microbiome is observed in the elderly participants, with Prevotella and Treponema being the most significant genera. In participants with oral conditions such as mouth ulcers, bleeding or painful gum, our data show that Prevotella and Capnocytophaga are the most dominant genera as compared to the controls. Similar patterns were observed in participants with various smoking habits as compared to the non-smoking participants. Our data show that Streptococcus and Neisseria are more dominant among denture users, as compared to the non-denture users. Our data also show that, abnormal oral conditions are associated with a reduced microbial diversity and microbial richness. Moreover, in this study we show that frequent coffee drinkers have higher microbial diversity compared to the non-drinkers, indicating that coffee may cause changes to the salivary microbiome. Furthermore, tea drinkers show higher microbial richness as compared to the non-tea drinkers.<br><br>CONCLUSION: This is the first study to assess the salivary microbiome in an Arab population, and one of the largest population-based studies aiming to the characterize the salivary microbiome composition and its association with age, oral health, denture use, smoking and coffee-tea consumption.}, }
@article {pmid32167855, year = {2020}, author = {Belmok, A and de Cena, JA and Kyaw, CM and Damé-Teixeira, N}, title = {The Oral Archaeome: A Scoping Review.}, journal = {Journal of dental research}, volume = {99}, number = {6}, pages = {630-643}, doi = {10.1177/0022034520910435}, pmid = {32167855}, issn = {1544-0591}, mesh = {Archaea/genetics ; *Dental Caries ; Humans ; *Microbiota ; Mouth ; Phylogeny ; }, abstract = {The Archaea domain was recognized as a separate phylogenetic lineage in the tree of life nearly 3 decades ago. It is now known as part of the human microbiome; however, given that its roles in oral sites are still poorly understood, this review aimed to establish the current level of evidence regarding archaea in the oral cavity to guide future research, providing insights on the present knowledge about the human oral archaeome. A scoping review was conducted with the PRISMA Extension for Scoping Reviews checklist. Five electronic databases were searched, as well as gray literature. Two independent reviewers performed the selection and characterization of the studies. Clinical studies were included when the target population consisted of humans of any age who were donors of samples from the oral cavity. A qualitative analysis was performed, based on the type of oral site and by considering the methods employed for archaeal identification and taxonomy, including the DNA extraction protocols, primers, and probes used. Fifty articles were included in the final scoping review, published from 1987 to 2019. Most studies sampled periodontal sites. Methanogens were the most abundant archaea in those sites, and their presence could be associated with other periodontal pathogens. No consistent relationship with different disease conditions was observed in studies that evaluated the microbiota surviving in endodontic sites. Few articles analyzed the presence of archaea in dental caries, saliva, or tongue microbiota, as well as in archaeologic samples, also showing a relationship with healthy microbiota. Archaea have been detected in different oral niches of individuals from diverse geographic locations and clinical conditions, suggesting potential roles in oral diseases. Methodological limitations may hamper our current knowledge about archaeal diversity and prevalence in oral samples, and future research with diversified methodological approaches may lead to a better comprehension of the human oral archaeome.}, }
@article {pmid32167023, year = {2020}, author = {Depommier, C and Van Hul, M and Everard, A and Delzenne, NM and De Vos, WM and Cani, PD}, title = {Pasteurized Akkermansia muciniphila increases whole-body energy expenditure and fecal energy excretion in diet-induced obese mice.}, journal = {Gut microbes}, volume = {11}, number = {5}, pages = {1231-1245}, pmid = {32167023}, issn = {1949-0984}, mesh = {Adipose Tissue/physiology ; Adipose Tissue, Brown/physiology ; Akkermansia ; Animals ; Carrier Proteins/genetics/metabolism ; Diet, High-Fat ; Dietary Carbohydrates/metabolism ; *Energy Metabolism ; Feces/*chemistry ; *Gastrointestinal Microbiome ; Gene Expression Regulation ; Intestinal Absorption ; Intestinal Mucosa/cytology ; Lipid Metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Obesity/*metabolism/*prevention &amp; control ; Oxygen Consumption ; Pasteurization ; Perilipin-2/genetics/metabolism ; Physical Conditioning, Animal ; Weight Gain ; }, abstract = {Accumulating evidence points to Akkermansia muciniphila as a novel candidate to prevent or treat obesity-related metabolic disorders. We recently observed, in mice and in humans, that pasteurization of A. muciniphila increases its beneficial effects on metabolism. However, it is currently unknown if the observed beneficial effects on body weight and fat mass gain are due to specific changes in energy expenditure. Therefore, we investigated the effects of pasteurized A. muciniphila on whole-body energy metabolism during high-fat diet feeding by using metabolic chambers. We confirmed that daily oral administration of pasteurized A. muciniphila alleviated diet-induced obesity and decreased food energy efficiency. We found that this effect was associated with an increase in energy expenditure and spontaneous physical activity. Strikingly, we discovered that energy expenditure was enhanced independently from changes in markers of thermogenesis or beiging of the white adipose tissue. However, we found in brown and white adipose tissues that perilipin2, a factor associated with lipid droplet and known to be altered in obesity, was decreased in expression by pasteurized A. muciniphila. Finally, we observed that treatment with pasteurized A. muciniphila increased energy excretion in the feces. Interestingly, we demonstrated that this effect was not due to the modulation of intestinal lipid absorption or chylomicron synthesis but likely involved a reduction of carbohydrates absorption and enhanced intestinal epithelial turnover. In conclusion, this study further dissects the mechanisms by which pasteurized A. muciniphila reduces body weight and fat mass gain. These data also further support the impact of targeting the gut microbiota by using specific bacteria to control whole-body energy metabolism.}, }
@article {pmid32166902, year = {2020}, author = {Antosca, K and Hoen, AG and Palys, T and Hilliard, M and Morrison, HG and Coker, M and Madan, J and Karagas, MR}, title = {Reliability of stool microbiome methods for DNA yields and sequencing among infants and young children.}, journal = {MicrobiologyOpen}, volume = {9}, number = {5}, pages = {e1018}, pmid = {32166902}, issn = {2045-8827}, support = {UH3 OD023275/OD/NIH HHS/United States ; R01 LM012723/LM/NLM NIH HHS/United States ; P01 ES022832/ES/NIEHS NIH HHS/United States ; T32 HL134598/HL/NHLBI NIH HHS/United States ; P20 GM104416/GM/NIGMS NIH HHS/United States ; }, mesh = {Child, Preschool ; Cohort Studies ; DNA, Bacterial/*isolation &amp; purification ; Feces/*microbiology ; Gastrointestinal Microbiome ; High-Throughput Nucleotide Sequencing/*methods ; Humans ; Infant ; RNA, Ribosomal, 16S/genetics ; Reproducibility of Results ; Specimen Handling/*methods ; }, abstract = {With the emergence of large-scale epidemiologic human microbiome studies, there is a need to understand the reproducibility of microbial DNA sequencing and the impact of specimen collection and processing methods on measures of microbial community composition and structure, with reproducibility studies in infants and young children particularly lacking. Here, we examined batch-to-batch variability and reliability of collection, handling, and processing protocols, testing replicate stool samples from infants and young children using Illumina MiSeq sequencing of the bacterial 16S rRNA gene V4-V5 hypervariable region, evaluating 33 conditions with different protocols and extraction methods. We detected no evidence of batch effects in replicate DNA samples or extractions from the same stool sample. Variability in DNA yield and alpha diversity was observed between the different collection, handling, and processing protocols. However, across all protocols, subject variability was the dominant contributor to microbiome structure, with comparatively little impact of the protocol used. While collection method and DNA extraction kit may affect DNA yield, and correspondingly alpha diversity, our findings suggest that characterization of the structure and composition of the fecal microbiome of infants and young children are reliably measurable by standardized collection, handling, and processing protocols and DNA extraction methods within an individual longitudinal study.}, }
@article {pmid32158700, year = {2020}, author = {Romani, L and Del Chierico, F and Chiriaco, M and Foligno, S and Reddel, S and Salvatori, G and Cifaldi, C and Faraci, S and Finocchi, A and Rossi, P and Bagolan, P and D'Argenio, P and Putignani, L and Fusaro, F}, title = {Gut Mucosal and Fecal Microbiota Profiling Combined to Intestinal Immune System in Neonates Affected by Intestinal Ischemic Injuries.}, journal = {Frontiers in cellular and infection microbiology}, volume = {10}, number = {}, pages = {59}, pmid = {32158700}, issn = {2235-2988}, mesh = {Feces ; *Gastrointestinal Microbiome ; Gastrointestinal Tract ; Humans ; Immune System ; Infant, Newborn ; *Microbiota ; }, abstract = {Background and Purpose: Early life microbiota plays a crucial role in human health by acting as a barrier from pathogens' invasion and maintaining the intestinal immune homoeostasis. Altered fecal microbiota (FM) ecology was reported in newborns affected by intestinal ischemia. Our purpose was to describe, in these patients, the FM, the mucosal microbiota (MM) and the mucosal immunity. Methods: Fourteen newborns underwent intestinal resection because of intestinal ischemia. FM and MM were determined through targeted-metagenomics, diversity assignment and Kruskal-Wallis analyses of Operational taxonomic units (OTUs). The mucosal immune cells were analyzed through cytofluorimetry. Results and Conclusion: Based on the severity intestinal injueris we identified two groups: extensive (EII) and focal intestinal ischemia (FII). FM and MM varied in EII and FII groups, showing in the EII group the predominance of Proteobacteria and Enterobacteriaceae and the reduction of Bacteroidetes and Verrucomicrobia for both microbiota. The MM was characterized by a statistically significant reduction of Bacteroides, Lachnospiraceae and Ruminococcaceae and by a higher diversity in the EII compared to FII group. FM showed a prevalence of Proteobacteria, while the Shannon index was lower in the EII compared to FII group. An overall increment in B- and T-lymphocytes and Natural killer (NK) T-like cells was found for EII mucosal samples associated to an increment of TNF-α and INF-γ expressing cells, compared to FII group. FM and MM carry specific signatures of intestinal ischemic lesions. Further research may be crucial to address the role of specific taxa in EII, expecially with reference to inflammation grade and ischemia extension.}, }
@article {pmid32156071, year = {2020}, author = {Pan, S and Hullar, MAJ and Lai, LA and Peng, H and May, DH and Noble, WS and Raftery, D and Navarro, SL and Neuhouser, ML and Lampe, PD and Lampe, JW and Chen, R}, title = {Gut Microbial Protein Expression in Response to Dietary Patterns in a Controlled Feeding Study: A Metaproteomic Approach.}, journal = {Microorganisms}, volume = {8}, number = {3}, pages = {}, pmid = {32156071}, issn = {2076-2607}, support = {R01 CA192222/NH/NIH HHS/United States ; P30 CA015704/CA/NCI NIH HHS/United States ; U54 CA116847/NH/NIH HHS/United States ; R01 CA211892/CA/NCI NIH HHS/United States ; R01 CA192222/CA/NCI NIH HHS/United States ; R01 CA211892/NH/NIH HHS/United States ; P30 CA015704/NH/NIH HHS/United States ; }, abstract = {Although the gut microbiome has been associated with dietary patterns linked to health, microbial metabolism is not well characterized. This ancillary study was a proof of principle analysis for a novel application of metaproteomics to study microbial protein expression in a controlled dietary intervention. We measured the response of the microbiome to diet in a randomized crossover dietary intervention of a whole-grain, low glycemic load diet (WG) and a refined-grain, high glycemic load diet (RG). Total proteins in stools from 9 participants at the end of each diet period (n = 18) were analyzed by LC MS/MS and proteins were identified using the Human Microbiome Project (HMP) human gut microbiome database and UniProt human protein databases. T-tests, controlling for false discovery rate (FDR) <10%, were used to compare the Gene Ontology (GO) biological processes and bacterial enzymes between the two interventions. Using shotgun proteomics, more than 53,000 unique peptides were identified including microbial (89%) and human peptides (11%). Forty-eight bacterial enzymes were statistically different between the diets, including those implicated in SCFA production and degradation of fatty acids. Enzymes associated with degradation of human mucin were significantly enriched in the RG diet. These results illustrate that the metaproteomic approach is a valuable tool to study the microbial metabolism of diets that may influence host health.}, }
@article {pmid32153643, year = {2020}, author = {Ma, Y and Liu, G and Ma, Y and Chen, Q}, title = {Integrative Analysis for Identifying Co-Modules of Microbe-Disease Data by Matrix Tri-Factorization With Phylogenetic Information.}, journal = {Frontiers in genetics}, volume = {11}, number = {}, pages = {83}, pmid = {32153643}, issn = {1664-8021}, abstract = {Microbe-disease association relationship mining is drawing more and more attention due to its potential in capturing disease-related microbes. Hence, it is essential to develop new tools or algorithms to study the complex pathogenic mechanism of microbe-related diseases. However, previous research studies mainly focused on the paradigm of "one disease, one microbe," rarely investigated the cooperation and associations between microbes, diseases or microbe-disease co-modules from system level. In this study, we propose a novel two-level module identifying algorithm (MDNMF) based on nonnegative matrix tri-factorization which integrates two similarity matrices (disease and microbe similarity matrices) and one microbe-disease association matrix into the objective of MDNMF. MDNMF can identify the modules from different levels and reveal the connections between these modules. In order to improve the efficiency and effectiveness of MDNMF, we also introduce human symptoms-disease network and microbial phylogenetic distance into this model. Furthermore, we applied it to HMDAD dataset and compared it with two NMF-based methods to demonstrate its effectiveness. The experimental results show that MDNMF can obtain better performance in terms of enrichment index (EI) and the number of significantly enriched taxon sets. This demonstrates the potential of MDNMF in capturing microbial modules that have significantly biological function implications.}, }
@article {pmid32133297, year = {2020}, author = {Cheng, H and Wang, Z and Cui, L and Wen, Y and Chen, X and Gong, F and Yi, H}, title = {Opportunities and Challenges of the Human Microbiome in Ovarian Cancer.}, journal = {Frontiers in oncology}, volume = {10}, number = {}, pages = {163}, pmid = {32133297}, issn = {2234-943X}, abstract = {Ovarian cancer is the most lethal malignancy among gynecological cancers worldwide. Most ovarian cancer patients are diagnosed at an advanced stage because of non-specific clinical symptoms. The human microbiome plays a crucial role in maintaining the normal physiological and pathological state of the body. With the development of technologies such as DNA and 16S rRNA sequencing, an increasing number of findings on the role of microbiome in cancers are being reported. Microbiome abnormalities are increasingly associated with diseases, including cancer development, and response to therapies. Some studies have shown the relationship between microbiome changes and ovarian cancer. However, the mechanisms underlying this relationship are not yet fully understood. Here, we summarize the key findings in this regard by focusing on estrogen metabolism and host recognition receptors in microorganisms and changes in the gut or pelvic microbiome in patients with ovarian cancer. We further discuss the potential of using the microbiome as a novel biomarker for cancers. We also highlight the possibility to use microorganisms as a treatment modality to enhance the immune system, activate anti-tumor response, mediate chemotherapy resistance, and ameliorate the adverse effects of the treatment.}, }
@article {pmid32132244, year = {2020}, author = {Bellone, M and Brevi, A and Huber, S}, title = {Microbiota-Propelled T Helper 17 Cells in Inflammatory Diseases and Cancer.}, journal = {Microbiology and molecular biology reviews : MMBR}, volume = {84}, number = {2}, pages = {}, pmid = {32132244}, issn = {1098-5557}, mesh = {Animals ; Humans ; Immunity ; Inflammation/complications/*microbiology ; Mice ; Microbiota/*immunology ; Neoplasms/immunology/*microbiology ; Th17 Cells/*immunology ; }, abstract = {Technologies allowing genetic sequencing of the human microbiome are opening new realms to discovery. The host microbiota substantially impacts immune responses both in immune-mediated inflammatory diseases (IMIDs) and in tumors affecting tissues beyond skin and mucosae. However, a mechanistic link between host microbiota and cancer or IMIDs has not been well established. Here, we propose T helper 17 (TH17) lymphocytes as the connecting factor between host microbiota and rheumatoid or psoriatic arthritides, multiple sclerosis, breast or ovarian cancer, and multiple myeloma. We theorize that similar mechanisms favor the expansion of gut-borne TH17 cells and their deployment at the site of inflammation in extraborder IMIDs and tumors, where TH17 cells are driving forces. Thus, from a pathogenic standpoint, tumors may share mechanistic routes with IMIDs. A review of similarities and divergences in microbiota-TH17 cell interactions in IMIDs and cancer sheds light on previously ignored pathways in either one of the two groups of pathologies and identifies novel therapeutic avenues.}, }
@article {pmid32129192, year = {2020}, author = {Vairakkani, R and Fernando, ME and Raj, TY}, title = {Metabolome and microbiome in kidney diseases.}, journal = {Saudi journal of kidney diseases and transplantation : an official publication of the Saudi Center for Organ Transplantation, Saudi Arabia}, volume = {31}, number = {1}, pages = {1-9}, doi = {10.4103/1319-2442.279927}, pmid = {32129192}, issn = {1319-2442}, mesh = {*Gastrointestinal Microbiome ; Humans ; *Kidney Diseases/metabolism/microbiology/physiopathology/therapy ; *Metabolome ; }, abstract = {Despite several decades of intensive research and hard work in nephrology, a void exists in the availability of markers for identifying at-risk individuals, diagnosing diseases at incipient stage, and predicting treatment response. Most of the current widely available diagnostic tools such as creatinine, urine analysis, and imaging studies are quite insensitive such that about half of the kidney function is lost before perceivable changes are observed with these tests. In addition, these parameters are affected by factors other than renal, questioning their specificity. Renal biopsy, though specific, is quite expensive, risky, and invasive. The recent surge in the knowledge of small molecules in the tissue and body fluids, "metabolomics," thanks to the Human Metabolome Database created by the Human Metabolome Project, has opened a new avenue for better understanding the disease pathogenesis and, in parallel, to identify novel biomarkers and druggable targets. Kidney, by virtue of its metabolic machinery and also being a major handler of metabolites generated by other tissues, is very much amenable to the metabolomic approach of studying its various perturbations. The gut microbiome, characterized by the Human Microbiome Project, is one of the principal players in metabolomics. Changes in metabolite profile due to alterations in gut microbiome can occur either as a cause or consequence of renal diseases. Unmasking the renal-metabolome-microbiome link has a great potential to script a new era in the diagnosis and management of renal diseases.}, }
@article {pmid32121205, year = {2020}, author = {Sare, AR and Stouvenakers, G and Eck, M and Lampens, A and Goormachtig, S and Jijakli, MH and Massart, S}, title = {Standardization of Plant Microbiome Studies: Which Proportion of the Microbiota is Really Harvested?.}, journal = {Microorganisms}, volume = {8}, number = {3}, pages = {}, pmid = {32121205}, issn = {2076-2607}, support = {FIRA 5200818F//Fonds De La Recherche Scientifique - FNRS/ ; }, abstract = {Studies in plant-microbiome currently use diverse protocols, making their comparison difficult and biased. Research in human microbiome have faced similar challenges, but the scientific community proposed various recommendations which could also be applied to phytobiome studies. Here, we addressed the isolation of plant microbiota through apple carposphere and lettuce root microbiome. We demonstrated that the fraction of the culturable epiphytic microbiota harvested by a single wash might only represent one-third of the residing microbiota harvested after four successive washes. In addition, we observed important variability between the efficiency of washing protocols (up to 1.6-fold difference for apple and 1.9 for lettuce). QIIME2 analysis of 16S rRNA gene, showed a significant difference of the alpha and beta diversity between protocols in both cases. The abundance of 76 taxa was significantly different between protocols used for apple. In both cases, differences between protocols disappeared when sequences of the four washes were pooled. Hence, pooling the four successive washes increased the alpha diversity for apple in comparison to a single wash. These results underline the interest of repeated washing to leverage abundance of microbial cells harvested from plant epiphytic microbiota whatever the washing protocols, thus minimizing bias.}, }
@article {pmid32117102, year = {2020}, author = {Tsigalou, C and Konstantinidis, T and Stavropoulou, E and Bezirtzoglou, EE and Tsakris, A}, title = {Potential Elimination of Human Gut Resistome by Exploiting the Benefits of Functional Foods.}, journal = {Frontiers in microbiology}, volume = {11}, number = {}, pages = {50}, pmid = {32117102}, issn = {1664-302X}, abstract = {Recent advances in technology over the last decades have strived to elucidate the diverse and abundant ecosystem of the human microbiome. The intestinal microbiota represents a densely inhabited environment that offers a plethora of beneficial effects to the host's wellbeing. On the other hand, it can serve as a potential reservoir of Multi-Drug Resistant (MDR) bacteria and their antibiotic-resistant genes (ARgenes), which comprise the "gut resistome." ARgenes, like antibiotics, have been omnipresent in the environment for billions of years. In the context of the gut microbiome, these genes may conflate into exogenous MDR or emerge in commensals due to mutations or gene transfers. It is currently generally accepted that Antimicrobial Resistance (AMR) poses a serious threat to public health worldwide. It is of paramount importance that researchers focus on, amongst other parameters, elaborating strategies to manage the gut resistome, particularly focusing on the diminution of AMR. Potential interventions in the gut microbiome field by Fecal Microbiota Transplant (FMT) or functional foods are newly emerged candidates for the uprooting of MDR strains and restoring dysbiosis and resilience. Probiotic nutrition is thought to diminish gut colonization from pathobionts. Yet only a few studies have explored the effects of antibiotics use on the reservoir of AR genes and the demanding time for return to normal by gut microbiota-targeted strategies. Regular administration of probiotic bacteria has recently been linked to restoration of the gut ecosystem and decrease of the gut resistome and AR genes carriers. This review summarizes the latest information about the intestinal resistome and the intriguing methods of fighting against AMR through probiotic-based methods and gut microbial shifts that have been proposed. This study contains some key messages: (1) AMR currently poses a lethal threat to global health, and it is pivotal for the scientific community to do its utmost in fighting against it; (2) human gut microbiome research, within the last decade especially, seems to be preoccupied with the interface of numerous diseases and identifying a potential target for a variety of interventions; (3) the gut resistome, comprised of AR genesis, presents very early on in life and is prone to shifts due to the use of antibiotics or dietary supplements; and (4) future strategies involving functional foods seem promising for the battle against AMR through intestinal resistome diminution.}, }
@article {pmid32112046, year = {2020}, author = {Domingue, JC and Drewes, JL and Merlo, CA and Housseau, F and Sears, CL}, title = {Host responses to mucosal biofilms in the lung and gut.}, journal = {Mucosal immunology}, volume = {13}, number = {3}, pages = {413-422}, pmid = {32112046}, issn = {1935-3456}, support = {K99 CA230192/CA/NCI NIH HHS/United States ; R01 CA203891/CA/NCI NIH HHS/United States ; R01 CA196845/CA/NCI NIH HHS/United States ; U2C CA233291/CA/NCI NIH HHS/United States ; /CRUK_/Cancer Research UK/United Kingdom ; }, mesh = {Animals ; *Biofilms/growth &amp; development ; Disease Susceptibility ; Gastrointestinal Microbiome/*immunology ; Host-Pathogen Interactions/*immunology ; Humans ; Immunity, Mucosal ; Inflammatory Bowel Diseases/etiology/metabolism/pathology ; Microbiota/*immunology ; Models, Biological ; Respiratory Mucosa/*immunology/*microbiology ; }, abstract = {The impact of the human microbiome on health and disease is of utmost importance and has been studied intensively in recent years. Microbes promote immune system development and are essential to the production and absorption of nutrients for the host but are also implicated in disease pathogenesis. Particularly, bacterial biofilms have long been recognized as contributors to chronic infections and diseases in humans. However, our understanding of how the host responds to the presence of biofilms, specifically the immune response to biofilms, and how this contributes to disease pathogenesis is limited. This review aims to highlight what is known about biofilm formation and in vivo models available for the biofilm study. We critique the contribution of biofilms to human diseases, focusing on the lung diseases, cystic fibrosis and chronic obstructive pulmonary disease, and the gut diseases, inflammatory bowel disease and colorectal cancer.}, }
@article {pmid32109571, year = {2020}, author = {Tarsillo, B and Priefer, R}, title = {Proteobiotics as a new antimicrobial therapy.}, journal = {Microbial pathogenesis}, volume = {142}, number = {}, pages = {104093}, doi = {10.1016/j.micpath.2020.104093}, pmid = {32109571}, issn = {1096-1208}, abstract = {Antibiotic resistance is a major concern for healthcare. The emergence of resistant bacteria has contributed to an increase in cost, morbidity, and mortality rates of patients. There is evidence to suggest that the inhibition of bacteria's virulence strategies would downregulate their pathogenesis and stop infections while also preventing more resistance. This concept became the backbone of many studies in the arena of human microbiome. Through probiotic studies, novel compounds were discovered that possessed antimicrobial activity. These have become labeled as proteobiotics, i.e. metabolites from probiotics. Proteobiotics have demonstrated the ability to interrupt bacteria cell-to-cell communication. Currently, there is one approved product containing proteobiotic technologies for swine showing positive outcomes.}, }
@article {pmid32109360, year = {2020}, author = {de Jesus, VC and Shikder, R and Oryniak, D and Mann, K and Alamri, A and Mittermuller, B and Duan, K and Hu, P and Schroth, RJ and Chelikani, P}, title = {Sex-Based Diverse Plaque Microbiota in Children with Severe Caries.}, journal = {Journal of dental research}, volume = {99}, number = {6}, pages = {703-712}, doi = {10.1177/0022034520908595}, pmid = {32109360}, issn = {1544-0591}, support = {//CIHR/Canada ; }, mesh = {Candida ; Child ; Child, Preschool ; *Dental Caries ; *Dental Plaque ; Female ; Humans ; Male ; *Microbiota ; Quality of Life ; RNA, Ribosomal, 16S ; Streptococcus mutans ; Veillonella ; }, abstract = {Severe early childhood caries (S-ECC) is a multifactorial disease that can lead to suffering and reduced oral health-related quality of life in young children. The bacterial and fungal composition of dental plaque and how children's sex is associated with S-ECC are largely unknown. In this study, V4-16S rRNA and ITS1 rRNA gene amplicon sequencing was used to compare the plaque bacteriome and mycobiome of children <72 mo of age: 40 with S-ECC (15 males, 25 females) and 40 caries-free (19 males, 21 females). Health- and nutrition-related questionnaire data were also investigated. This study aimed to analyze potential sex-based differences in the supragingival plaque microbiota of young children with S-ECC and those caries-free. Behavioral and nutritional habit differences were observed between children with S-ECC and those caries-free and between male and female children. Overall, higher levels of Veillonella dispar, Streptococcus mutans, and other bacterial species were found in the S-ECC group as compared with caries-free controls (P < 0.05). A significant difference in the abundance of Neisseria was observed between males and females with S-ECC (P < .05). Fungal taxonomic analysis showed significantly higher levels of Candida dubliniensis in the plaque of children with S-ECC as compared with those caries-free (P < 0.05), but no differences were observed with Candida albicans (P > 0.05). Significant differences in the relative abundance of Mycosphaerella, Cyberlindnera, and Trichosporon fungal species were also observed between the caries-free and S-ECC groups (P < 0.05). Machine learning analysis revealed the most important bacterial and fungal species for classifying S-ECC versus caries-free. Different patterns of crosstalk between microbial species were observed between male and female children. Our work demonstrates that plaque microbiota and sex may be important determinants for S-ECC and could be factors to consider for inclusion in caries risk assessment tools.}, }
@article {pmid32108360, year = {2020}, author = {Ruokolainen, L and Parkkola, A and Karkman, A and Sinkko, H and Peet, A and Hämäläinen, AM and von Hertzen, L and Tillmann, V and Koski, K and Virtanen, SM and Niemelä, O and Haahtela, T and Knip, M}, title = {Contrasting microbiotas between Finnish and Estonian infants: Exposure to Acinetobacter may contribute to the allergy gap.}, journal = {Allergy}, volume = {75}, number = {9}, pages = {2342-2351}, doi = {10.1111/all.14250}, pmid = {32108360}, issn = {1398-9995}, mesh = {*Acinetobacter ; Allergens ; Child ; Estonia/epidemiology ; Female ; Finland/epidemiology ; Humans ; *Hypersensitivity/epidemiology ; Infant ; *Microbiota ; }, abstract = {BACKGROUND: Allergic diseases are more common in Finland than in Estonia, which-according to the biodiversity hypothesis-could relate to differences in early microbial exposures.<br><br>METHODS: We aimed at defining possible microbial perturbations preceding early atopic sensitization. Stool, nasal and skin samples of 6-month-old DIABIMMUNE study participants with HLA susceptibility to type 1 diabetes were collected. We compared microbiotas of sensitized (determined by specific IgE results at 18&#xa0;months of age) and unsensitized Estonian and Finnish children.<br><br>RESULTS: Sensitization was differentially targeted between populations, as egg-specific and birch pollen-specific IgE was more common in Finland. Microbial diversity and community composition also differed; the genus Acinetobacter was more abundant in Estonian skin and nasal samples. Particularly, the strain-level profile of Acinetobacter lwoffii was more diverse in Estonian samples. Early microbiota was not generally associated with later sensitization. Microbial composition tended to differ between children with or without IgE-related sensitization, but only in Finland. While land-use pattern (ie green areas vs. urban landscapes around the children's homes) was not associated with microbiota as a whole, it associated with the composition of the genus Acinetobacter. Breastfeeding affected gut microbial composition and seemed to protect from sensitization.<br><br>CONCLUSIONS: In accordance with the biodiversity hypothesis, our results support disparate early exposure to environmental microbes between Finnish and Estonian children and suggest a significant role of the genus Acinetobacter in the allergy gap between the two populations. The significance of the observed differences for later allergic sensitization remains open.}, }
@article {pmid32103766, year = {2020}, author = {Shen, L}, title = {Gut, oral and nasal microbiota and Parkinson's disease.}, journal = {Microbial cell factories}, volume = {19}, number = {1}, pages = {50}, pmid = {32103766}, issn = {1475-2859}, mesh = {Humans ; Intestines/*microbiology ; *Microbiota ; Mouth/*microbiology ; Nose/*microbiology ; Parkinson Disease/*microbiology ; }, abstract = {Parkinson's disease (PD) is the second most prevalent neurodegenerative disease, and in an effort to identify novel therapeutic target for this disease in recent years, human microbiota has attracted much interest. This paper briefly summarizes the main findings concerning the differences of human microbiome across several important mucosal interfaces, including nose, mouth, and gut between PD patients and controls as obtained from a total of 13 studies published since 2015, which covered a total of 943 PD patients and 831 matched controls from 6 countries. Overall, these studies supported the differences of gut microbiota between PD patients and matched controls, while significantly altered bacterial taxa among studies were not identical. Due to relatively limited number of available studies and covered patients, the associations between oral and nasal microbiota and PD remain inconclusive. The therapeutic and diagnostic potentials of gut microbiota for PD are discussed. More well-designed clinical studies recruiting large-scale PD patients are encouraged in future.}, }
@article {pmid32103319, year = {2020}, author = {Ulaszewska, MM and Koutsos, A and Trošt, K and Stanstrup, J and Garcia-Aloy, M and Scholz, M and Fava, F and Natella, F and Scaccini, C and Vrhovsek, U and Tuohy, K and Lovegrove, J and Mattivi, F}, title = {Two apples a day modulate human:microbiome co-metabolic processing of polyphenols, tyrosine and tryptophan.}, journal = {European journal of nutrition}, volume = {59}, number = {8}, pages = {3691-3714}, doi = {10.1007/s00394-020-02201-8}, pmid = {32103319}, issn = {1436-6215}, support = {FOODBALL//Joint Programming Initiative A healthy diet for a healthy life/ ; CABALA_DIET&amp;HEALTH//Joint Programming Initiative A healthy diet for a healthy life/ ; }, mesh = {Biomarkers ; Humans ; *Malus ; *Microbiota ; Polyphenols/analysis ; Reproducibility of Results ; Tryptophan ; Tyrosine ; }, abstract = {PURPOSE: Validated biomarkers of food intake (BFIs) have recently been suggested as a useful tool to assess adherence to dietary guidelines or compliance in human dietary interventions. Although many new candidate biomarkers have emerged in the last decades for different foods from metabolic profiling studies, the number of comprehensively validated biomarkers of food intake is limited. Apples are among the most frequently consumed fruits and a rich source of polyphenols and fibers, an important mediator for their health-protective properties.<br><br>METHODS: Using an untargeted metabolomics approach, we aimed to identify biomarkers of long-term apple intake and explore how apples impact on the human plasma and urine metabolite profiles. Forty mildly hypercholesterolemic volunteers consumed two whole apples or a sugar and energy-matched control beverage, daily for 8&#xa0;weeks in a randomized, controlled, crossover intervention study. The metabolome in plasma and urine samples was analyzed via untargeted metabolomics.<br><br>RESULTS: We found 61 urine and 9 plasma metabolites being statistically significant after the whole apple intake compared to the control beverage, including several polyphenol metabolites that could be used as BFIs. Furthermore, we identified several endogenous indole and phenylacetyl-glutamine microbial metabolites significantly increasing in urine after apple consumption. The multiomic dataset allowed exploration of the correlations between metabolites modulated significantly by the dietary intervention and fecal microbiota species at genus level, showing interesting interactions between Granulicatella genus and phenyl-acetic acid metabolites. Phloretin glucuronide and phloretin glucuronide sulfate appeared promising biomarkers of apple intake; however, robustness, reliability and stability data are needed for full BFI validation.<br><br>CONCLUSION: The identified apple BFIs can be used in future studies to assess compliance and to explore their health effects after apple intake. Moreover, the identification of polyphenol microbial metabolites suggests that apple consumption mediates significant gut microbial metabolic activity which should be further explored.}, }
@article {pmid32103176, year = {2020}, author = {Quinn, RA and Melnik, AV and Vrbanac, A and Fu, T and Patras, KA and Christy, MP and Bodai, Z and Belda-Ferre, P and Tripathi, A and Chung, LK and Downes, M and Welch, RD and Quinn, M and Humphrey, G and Panitchpakdi, M and Weldon, KC and Aksenov, A and da Silva, R and Avila-Pacheco, J and Clish, C and Bae, S and Mallick, H and Franzosa, EA and Lloyd-Price, J and Bussell, R and Thron, T and Nelson, AT and Wang, M and Leszczynski, E and Vargas, F and Gauglitz, JM and Meehan, MJ and Gentry, E and Arthur, TD and Komor, AC and Poulsen, O and Boland, BS and Chang, JT and Sandborn, WJ and Lim, M and Garg, N and Lumeng, JC and Xavier, RJ and Kazmierczak, BI and Jain, R and Egan, M and Rhee, KE and Ferguson, D and Raffatellu, M and Vlamakis, H and Haddad, GG and Siegel, D and Huttenhower, C and Mazmanian, SK and Evans, RM and Nizet, V and Knight, R and Dorrestein, PC}, title = {Global chemical effects of the microbiome include new bile-acid conjugations.}, journal = {Nature}, volume = {579}, number = {7797}, pages = {123-129}, pmid = {32103176}, issn = {1476-4687}, support = {P01 HL088093/HL/NHLBI NIH HHS/United States ; GMS10RR029121/NH/NIH HHS/United States ; R24DK110499/NH/NIH HHS/United States ; P30 DK043351/DK/NIDDK NIH HHS/United States ; UL1 TR001863/TR/NCATS NIH HHS/United States ; 1 DP1 AT010885/NH/NIH HHS/United States ; 1R01HL116235/NH/NIH HHS/United States ; KL2 TR001444/TR/NCATS NIH HHS/United States ; R37 DK057978/DK/NIDDK NIH HHS/United States ; T32 DK007494/DK/NIDDK NIH HHS/United States ; R03 CA211211/CA/NCI NIH HHS/United States ; R24 DK110499/DK/NIDDK NIH HHS/United States ; P30 DK040561/DK/NIDDK NIH HHS/United States ; R01 HL105278/HL/NHLBI NIH HHS/United States ; R01 HD084163/HD/NICHD NIH HHS/United States ; R01 GM107550/GM/NIGMS NIH HHS/United States ; S10 RR029121/RR/NCRR NIH HHS/United States ; CA014195/CA/NCI NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; U01 AI124316/AI/NIAID NIH HHS/United States ; P42 ES010337/ES/NIEHS NIH HHS/United States ; R01 AI126277/AI/NIAID NIH HHS/United States ; DP1 AT010885/AT/NCCIH NIH HHS/United States ; 1R03CA211211-01/NH/NIH HHS/United States ; P30 DK120515/DK/NIDDK NIH HHS/United States ; U54 DE023798/DE/NIDCR NIH HHS/United States ; R01 HL116235/HL/NHLBI NIH HHS/United States ; T15 LM011271/LM/NLM NIH HHS/United States ; U54DE023798/NH/NIH HHS/United States ; 5U01AI124316-03/NH/NIH HHS/United States ; R01 DK057978/DK/NIDDK NIH HHS/United States ; P30 CA014195/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Bile Acids and Salts/*biosynthesis/*chemistry/metabolism ; Cholic Acid/biosynthesis/chemistry/metabolism ; Cystic Fibrosis/genetics/metabolism/microbiology ; Germ-Free Life ; Humans ; Inflammatory Bowel Diseases/genetics/metabolism/microbiology ; *Metabolomics ; Mice ; Microbiota/*physiology ; Receptors, Cytoplasmic and Nuclear/genetics/metabolism ; }, abstract = {A mosaic of cross-phylum chemical interactions occurs between all metazoans and their microbiomes. A number of molecular families that are known to be produced by the microbiome have a marked effect on the balance between health and disease[1-9]. Considering the diversity of the human microbiome (which numbers over 40,000 operational taxonomic units[10]), the effect of the microbiome on the chemistry of an entire animal remains underexplored. Here we use mass spectrometry informatics and data visualization approaches[11-13] to provide an assessment of the effects of the microbiome on the chemistry of an entire mammal by comparing metabolomics data from germ-free and specific-pathogen-free mice. We found that the microbiota affects the chemistry of all organs. This included the amino acid conjugations of host bile acids that were used to produce phenylalanocholic acid, tyrosocholic acid and leucocholic acid, which have not previously been characterized despite extensive research on bile-acid chemistry[14]. These bile-acid conjugates were also found in humans, and were enriched in patients with inflammatory bowel disease or cystic fibrosis. These compounds agonized the farnesoid X receptor in vitro, and mice gavaged with the compounds showed reduced expression of bile-acid synthesis genes in vivo. Further studies are required to confirm whether these compounds have a physiological role in the host, and whether they contribute to gut diseases that are associated with microbiome dysbiosis.}, }
@article {pmid32102941, year = {2020}, author = {Wu, L and Zeng, T and Deligios, M and Milanesi, L and Langille, MGI and Zinellu, A and Rubino, S and Carru, C and Kelvin, DJ}, title = {Age-Related Variation of Bacterial and Fungal Communities in Different Body Habitats across the Young, Elderly, and Centenarians in Sardinia.}, journal = {mSphere}, volume = {5}, number = {1}, pages = {}, pmid = {32102941}, issn = {2379-5042}, mesh = {Adult ; *Age Factors ; Aged ; Aged, 80 and over ; *Aging ; Bacteria/*classification ; DNA, Intergenic/genetics ; Ecosystem ; Feces/microbiology ; Female ; Fungi/classification/*genetics ; Gastrointestinal Microbiome ; Gastrointestinal Tract/microbiology ; Humans ; Italy ; Male ; *Microbiota ; Mouth/microbiology ; *Mycobiome ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; Skin/microbiology ; Young Adult ; }, abstract = {Human body microbes interact with the host, forming microbial communities that are in continual flux during the aging process. Previous studies have mostly focused on surveying a single body habitat to determine the age-related variation in the bacterial and fungal communities. A more comprehensive understanding of the variation in the human microbiota and mycobiota across multiple body habitats related to aging is still unclear. To obtain an integrated view of the spatial distribution of microbes in a specific Mediterranean population across a wide age range, we surveyed the bacterial and fungal communities in the skin, oral cavity, and gut in the young, elderly, and centenarians in Sardinia using 16S rRNA gene and internal transcribed spacer 1 (ITS1) sequencing. We found that the distribution and correlation of bacterial and fungal communities in Sardinians were largely determined by body site. In each age group, the bacterial and fungal communities found in the skin were significantly different in structure. In the oral cavity, age had a marginal impact on the structures of the bacterial and fungal communities. Furthermore, the gut bacterial communities in centenarians clustered separately from those of the young and elderly, while the fungal communities in the gut habitat could not be separated by host age.IMPORTANCE Site-specific microbial communities are recognized as important factors in host health and disease. To better understand how the human microbiota potentially affects and is affected by its host during the aging process, the fundamental issue to address is the distribution of microbiota related to age. Here, we show an integrated view of the spatial distribution of microbes in a specific Mediterranean population (Sardinians) across a wide age range. Our study indicates that age plays a critical role in shaping the human microbiota in a habitat-dependent manner. The dynamic age-related microbiota changes we observed across multiple body sites may provide possibilities for modulating microbe communities to maintain or improve health during aging.}, }
@article {pmid32102343, year = {2020}, author = {Lopez-Santamarina, A and Miranda, JM and Mondragon, ADC and Lamas, A and Cardelle-Cobas, A and Franco, CM and Cepeda, A}, title = {Potential Use of Marine Seaweeds as Prebiotics: A Review.}, journal = {Molecules (Basel, Switzerland)}, volume = {25}, number = {4}, pages = {}, pmid = {32102343}, issn = {1420-3049}, mesh = {Animals ; Chlorophyceae/chemistry ; Dietary Fiber/metabolism/*pharmacology ; Fermentation ; Gastrointestinal Microbiome/*drug effects/physiology ; Humans ; Mice ; Microbiota/*drug effects/physiology ; Phaeophyceae/chemistry ; Polysaccharides/chemistry/isolation &amp; purification/*pharmacology ; Prebiotics/*analysis/supply &amp; distribution ; Rats ; Rhodophyta/chemistry ; Seaweed/*chemistry ; }, abstract = {Human gut microbiota plays an important role in several metabolic processes and human diseases. Various dietary factors, including complex carbohydrates, such as polysaccharides, provide abundant nutrients and substrates for microbial metabolism in the gut, affecting the members and their functionality. Nowadays, the main sources of complex carbohydrates destined for human consumption are terrestrial plants. However, fresh water is an increasingly scarce commodity and world agricultural productivity is in a persistent decline, thus demanding the exploration of other sources of complex carbohydrates. As an interesting option, marine seaweeds show rapid growth and do not require arable land, fresh water or fertilizers. The present review offers an objective perspective of the current knowledge surrounding the impacts of seaweeds and their derived polysaccharides on the human microbiome and the profound need for more in-depth investigations into this topic. Animal experiments and in vitro colonic-simulating trials investigating the effects of seaweed ingestion on human gut microbiota are discussed.}, }
@article {pmid32101723, year = {2020}, author = {Xavier, JB and Young, VB and Skufca, J and Ginty, F and Testerman, T and Pearson, AT and Macklin, P and Mitchell, A and Shmulevich, I and Xie, L and Caporaso, JG and Crandall, KA and Simone, NL and Godoy-Vitorino, F and Griffin, TJ and Whiteson, KL and Gustafson, HH and Slade, DJ and Schmidt, TM and Walther-Antonio, MRS and Korem, T and Webb-Robertson, BM and Styczynski, MP and Johnson, WE and Jobin, C and Ridlon, JM and Koh, AY and Yu, M and Kelly, L and Wargo, JA}, title = {The Cancer Microbiome: Distinguishing Direct and Indirect Effects Requires a Systemic View.}, journal = {Trends in cancer}, volume = {6}, number = {3}, pages = {192-204}, pmid = {32101723}, issn = {2405-8025}, support = {R01 CA208179/CA/NCI NIH HHS/United States ; KL2 TR002379/TR/NCATS NIH HHS/United States ; R01 CA227479/CA/NCI NIH HHS/United States ; P30 CA008748/CA/NCI NIH HHS/United States ; U54 CA209975/CA/NCI NIH HHS/United States ; }, mesh = {Analgesics, Opioid/therapeutic use ; Animals ; Bacteria/metabolism ; Central Nervous System/physiology ; Drug Synergism ; Environmental Microbiology ; Gastritis/microbiology ; Gastrointestinal Microbiome ; Helicobacter Infections/complications ; Host-Pathogen Interactions ; Humans ; Immunotherapy ; Mice ; *Microbiota/drug effects/radiation effects ; Neoplasms/etiology/*microbiology/therapy/virology ; Oncogenic Viruses/pathogenicity ; Probiotics ; Stomach Neoplasms/etiology/microbiology ; Symbiosis ; Tumor Virus Infections ; }, abstract = {The collection of microbes that live in and on the human body - the human microbiome - can impact on cancer initiation, progression, and response to therapy, including cancer immunotherapy. The mechanisms by which microbiomes impact on cancers can yield new diagnostics and treatments, but much remains unknown. The interactions between microbes, diet, host factors, drugs, and cell-cell interactions within the cancer itself likely involve intricate feedbacks, and no single component can explain all the behavior of the system. Understanding the role of host-associated microbial communities in cancer systems will require a multidisciplinary approach combining microbial ecology, immunology, cancer cell biology, and computational biology - a systems biology approach.}, }
@article {pmid32099373, year = {2020}, author = {Michael, H and Mpofana, T and Ramlall, S and Oosthuizen, F}, title = {The Role of Brain Derived Neurotrophic Factor in HIV-Associated Neurocognitive Disorder: From the Bench-Top to the Bedside.}, journal = {Neuropsychiatric disease and treatment}, volume = {16}, number = {}, pages = {355-367}, pmid = {32099373}, issn = {1176-6328}, abstract = {Human immunodeficiency virus (HIV)-associated neurocognitive disorder (HAND) remains prevalent in the anti-retroviral (ART) era. While there is a complex interplay of many factors in the neuropathogenesis of HAND, decreased neurotrophic synthesis has been shown to contribute to synaptic degeneration which is a hallmark of HAND neuropathology. Brain derived neurotrophic factor (BDNF) is the most abundant and synaptic-promoting neurotrophic factor in the brain and plays a critical role in both learning and memory. Reduced BDNF levels can worsen neurocognitive impairment in HIV-positive individuals across several domains. In this paper, we review the evidence from pre-clinical and clinical studies showing the neuroprotective roles of BDNF against viral proteins, effect on co-morbid mental health disorders, altered human microbiome and ART in HAND management. Potential applications of BDNF modulation in pharmacotherapeutic, cognitive and behavioral interventions in HAND are also discussed. Finally, research gaps and future research direction are identified with the aim of helping researchers to direct efforts to make these BDNF driven interventions improve the quality of life of patients living with HAND.}, }
@article {pmid32098835, year = {2020}, author = {Rosa, BA and Mihindukulasuriya, K and Hallsworth-Pepin, K and Wollam, A and Martin, J and Snowden, C and Dunne, WM and Weinstock, GM and Burnham, CA and Mitreva, M}, title = {Improving Characterization of Understudied Human Microbiomes Using Targeted Phylogenetics.}, journal = {mSystems}, volume = {5}, number = {1}, pages = {}, pmid = {32098835}, issn = {2379-5077}, support = {U54 HG004968/HG/NHGRI NIH HHS/United States ; }, abstract = {Whole-genome bacterial sequences are required to better understand microbial functions, niche-specific bacterial metabolism, and disease states. Although genomic sequences are available for many of the human-associated bacteria from commonly tested body habitats (e.g., feces), as few as 13% of bacterium-derived reads from other sites such as the skin map to known bacterial genomes. To facilitate a better characterization of metagenomic shotgun reads from underrepresented body sites, we collected over 10,000 bacterial isolates originating from 14 human body habitats, identified novel taxonomic groups based on full-length 16S rRNA gene sequences, clustered the sequences to ensure that no individual taxonomic group was overselected for sequencing, prioritized bacteria from underrepresented body sites (such as skin and respiratory and urinary tracts), and sequenced and assembled genomes for 665 new bacterial strains. Here, we show that addition of these genomes improved read mapping rates of Human Microbiome Project (HMP) metagenomic samples by nearly 30% for the previously underrepresented phylum Fusobacteria, and 27.5% of the novel genomes generated here had high representation in at least one of the tested HMP samples, compared to 12.5% of the sequences in the public databases, indicating an enrichment of useful novel genomic sequences resulting from the prioritization procedure. As our understanding of the human microbiome continues to improve and to enter the realm of therapy developments, targeted approaches such as this to improve genomic databases will increase in importance from both an academic and a clinical perspective.IMPORTANCE The human microbiome plays a critically important role in health and disease, but current understanding of the mechanisms underlying the interactions between the varying microbiome and the different host environments is lacking. Having access to a database of fully sequenced bacterial genomes provides invaluable insights into microbial functions, but currently sequenced genomes for the human microbiome have largely come from a limited number of body sites (primarily feces), while other sites such as the skin, respiratory tract, and urinary tract are underrepresented, resulting in as little as 13% of bacterium-derived reads mapping to known bacterial genomes. Here, we sequenced and assembled 665 new bacterial genomes, prioritized from a larger database to select underrepresented body sites and bacterial taxa in the existing databases. As a result, we substantially improve mapping rates for samples from the Human Microbiome Project and provide an important contribution to human bacterial genomic databases for future studies.}, }
@article {pmid32094388, year = {2020}, author = {Marsland, R and Cui, W and Mehta, P}, title = {A minimal model for microbial biodiversity can reproduce experimentally observed ecological patterns.}, journal = {Scientific reports}, volume = {10}, number = {1}, pages = {3308}, pmid = {32094388}, issn = {2045-2322}, support = {R35 GM119461/GM/NIGMS NIH HHS/United States ; }, mesh = {Bacteria/classification/metabolism ; *Biodiversity ; Humans ; Microbiota ; *Models, Biological ; Principal Component Analysis ; }, abstract = {Surveys of microbial biodiversity such as the Earth Microbiome Project (EMP) and the Human Microbiome Project (HMP) have revealed robust ecological patterns across different environments. A major goal in ecology is to leverage these patterns to identify the ecological processes shaping microbial ecosystems. One promising approach is to use minimal models that can relate mechanistic assumptions at the microbe scale to community-level patterns. Here, we demonstrate the utility of this approach by showing that the Microbial Consumer Resource Model (MiCRM) - a minimal model for microbial communities with resource competition, metabolic crossfeeding and stochastic colonization - can qualitatively reproduce patterns found in survey data including compositional gradients, dissimilarity/overlap correlations, richness/harshness correlations, and nestedness of community composition. By using the MiCRM to generate synthetic data with different environmental and taxonomical structure, we show that large scale patterns in the EMP can be reproduced by considering the energetic cost of surviving in harsh environments and HMP patterns may reflect the importance of environmental filtering in shaping competition. We also show that recently discovered dissimilarity-overlap correlations in the HMP likely arise from communities that share similar environments rather than reflecting universal dynamics. We identify ecologically meaningful changes in parameters that alter or destroy each one of these patterns, suggesting new mechanistic hypotheses for further investigation. These findings highlight the promise of minimal models for microbial ecology.}, }
@article {pmid32089572, year = {2020}, author = {Gupta, V and Kumar, R and Sood, U and Singhvi, N}, title = {Reconciling Hygiene and Cleanliness: A New Perspective from Human Microbiome.}, journal = {Indian journal of microbiology}, volume = {60}, number = {1}, pages = {37-44}, pmid = {32089572}, issn = {0046-8991}, abstract = {The term hygiene is deeply rooted with the concept of maintaining sound health and alertness towards cleanliness, while "hygiene hypothesis" depicts the protective role of microbial community exposure in development of early immunity and initial allergic and aesthetic reactions. The tug-of-war has now been pushed toward the literal term "hygiene" over the "hygiene hypothesis" and has continued with disinfection of all microbial loads from the related environments to avoid infections in humans. With the advancement in the microbiome studies, it became clear that humans possess warm, and significant relationships with diverse microbial community. With this opinion article, we have emphasized on the importance of hygiene hypothesis in immunological responses. We also propose the individual/targeted hygiene instead of application of unanimous hygiene hypothesis. This review also elaborates the common practices that should be employed to maintain hygiene along with the balanced microbiome.}, }
@article {pmid32089571, year = {2020}, author = {Singhvi, N and Gupta, V and Gaur, M and Sharma, V and Puri, A and Singh, Y and Dubey, GP and Lal, R}, title = {Interplay of Human Gut Microbiome in Health and Wellness.}, journal = {Indian journal of microbiology}, volume = {60}, number = {1}, pages = {26-36}, pmid = {32089571}, issn = {0046-8991}, abstract = {The gut microbiome analysis, with specific interest on their direct impact towards the human health, is currently revolutionizing the unexplored frontiers of the pathogenesis and wellness. Although in-depth investigations of gut microbiome, 'the Black Boxes', complexities and functionalities are yet at its infancy, profound evidences are being reported for their concurrent involvement in disease etiology and its treatment. Interestingly, studies from the 'minimal murine' (Oligo-MM[12]), 'humanized' microbiota gnotobiotic mice models and patient samples, combined with multi-omics and cell biology approaches, have been revealing the implications of these findings in the treatment of gut dysbiosis associated diseases. Nonetheless, due to the inherent heterogeneity of the gut commensals and their unified co-existence with opportunistic pathobionts, it is utmost essential to highlight their functionalities in 'good or bad' gut in human wellness. We have specifically reviewed dietary lifestyle and infectious diseases linked with the gut bacterial consortia to delineate the ecobiotic approaches towards their treatment. This notably includes gut mucosal immunity mediated diseases such as Tuberculosis, IBD, CDI, Type 2 Diabetes, etc. Alongside of each dysbiosis, we have described the current therapeutic advancements of the pre- and probiotics derived from human microbiome studies to restore gut microbial homeostasis. With a continuous running debate on the role of microbiota in above mentioned diseases, we have collected numerous scientific evidences highlighting a previously unanticipated complex involvement of gut microbiome in the potential of human health.}, }
@article {pmid32080334, year = {2020}, author = {Piersigilli, F and Syed, M and Lam, TT and Dotta, A and Massoud, M and Vernocchi, P and Quagliariello, A and Putignani, L and Auriti, C and Salvatori, G and Bagolan, P and Bhandari, V}, title = {An omic approach to congenital diaphragmatic hernia: a pilot study of genomic, microRNA, and metabolomic profiling.}, journal = {Journal of perinatology : official journal of the California Perinatal Association}, volume = {40}, number = {6}, pages = {952-961}, pmid = {32080334}, issn = {1476-5543}, mesh = {Genomics ; *Hernias, Diaphragmatic, Congenital/genetics ; Humans ; Infant, Newborn ; Lung ; Metabolomics ; *MicroRNAs/genetics ; Pilot Projects ; }, abstract = {INTRODUCTION: The omic approach can help identify a signature that can be potentially used as biomarkers in babies with congenital diaphragmatic hernia (CDH).<br><br>OBJECTIVES: To find a specific microRNA (miR) and metabolic fingerprint of the tracheal aspirates (TA) of CDH patients. We conducted a genetic analysis from blood samples.<br><br>METHODS: TA samples collected in the first 48&#x2009;h of life in patients with CDH, compared with age-matched controls. Metabolomics done by a mass spectroscopy-based assay. Genomics done using chromosomal microarray analysis.<br><br>RESULTS: CDH (n&#x2009;=&#x2009;17) and 16 control neonates enrolled. miR-16, miR-17, miR-18, miR-19b, and miR-20a had an increased expression, while miR-19a had a twofold decreased expression in CDH patients, compared with age-matched control patients. Specific metabolites separated neonates with CDH from controls. A genetic mutation found in a small subset of patients.<br><br>CONCLUSIONS: Specific patterns of metabolites and miR expression can be discerned in TA samples in infants with CDH.}, }
@article {pmid32077339, year = {2020}, author = {Grosse, CSJ and Christophersen, CT and Devine, A and Lawrance, IC}, title = {The role of a plant-based diet in the pathogenesis, etiology and management of the inflammatory bowel diseases.}, journal = {Expert review of gastroenterology &amp; hepatology}, volume = {14}, number = {3}, pages = {137-145}, doi = {10.1080/17474124.2020.1733413}, pmid = {32077339}, issn = {1747-4132}, mesh = {*Diet, Vegetarian/methods ; Dietary Fiber/therapeutic use ; Gastrointestinal Microbiome/physiology ; Humans ; Inflammation/complications/*diet therapy ; Inflammatory Bowel Diseases/*diet therapy/etiology/physiopathology ; }, abstract = {Introduction: Inflammatory Bowel Disease (IBD) carries a significant burden on an individual's quality-of-life and on the healthcare system. The majority of patients use dietary modifications to manage their symptoms, despite limited research to support these changes. There is emerging data that a plant-based diet will be of benefit to IBD patients.Areas covered: A literature review on the pathogenesis and potential benefits of dietary management of IBD.Expert opinion: A Westernized diet has been associated with IBD risk and relapse; hence a plant-based diet may be of benefit to IBD patients through reducing inflammation and restoring symbiosis. Dietary therapy can be an important adjunct therapy, however, better quality studies are still required.}, }
@article {pmid32076932, year = {2020}, author = {Bresalier, RS and Chapkin, RS}, title = {Human Microbiome in Health and Disease: The Good, the Bad, and the Bugly.}, journal = {Digestive diseases and sciences}, volume = {65}, number = {3}, pages = {671-673}, doi = {10.1007/s10620-020-06059-y}, pmid = {32076932}, issn = {1573-2568}, mesh = {Gastrointestinal Diseases/metabolism/*microbiology/pathology ; *Health Status ; Humans ; Microbiota/*physiology ; }, }
@article {pmid32076128, year = {2020}, author = {Darcy, JL and Washburne, AD and Robeson, MS and Prest, T and Schmidt, SK and Lozupone, CA}, title = {A phylogenetic model for the recruitment of species into microbial communities and application to studies of the human microbiome.}, journal = {The ISME journal}, volume = {14}, number = {6}, pages = {1359-1368}, pmid = {32076128}, issn = {1751-7370}, support = {T15 LM009451/LM/NLM NIH HHS/United States ; 5 T15 LM009451-12//U.S. Department of Health &amp; Human Services | NIH | U.S. National Library of Medicine (NLM)/International ; }, mesh = {Bacteria/classification/*genetics/isolation &amp; purification ; Feces/microbiology ; Female ; Gastrointestinal Microbiome ; Humans ; Infant ; Infant, Newborn ; Male ; *Microbiota ; *Phylogeny ; }, abstract = {Understanding when and why new species are recruited into microbial communities is a formidable problem with implications for managing microbial systems, for instance by helping us better understand whether a probiotic or pathogen would be expected to colonize a human microbiome. Much theory in microbial temporal dynamics is focused on how phylogenetic relationships between microbes impact the order in which those microbes are recruited; for example, species that are closely related may competitively exclude each other. However, several recent human microbiome studies have observed closely related bacteria being recruited into microbial communities in short succession, suggesting that microbial community assembly is historically contingent, but competitive exclusion of close relatives may not be important. To address this, we developed a mathematical model that describes the order in which new species are detected in microbial communities over time within a phylogenetic framework. We use our model to test three hypothetical assembly modes: underdispersion (species recruitment is more likely if a close relative was previously detected), overdispersion (recruitment is more likely if a close relative has not been previously detected), and the neutral model (recruitment likelihood is not related to phylogenetic relationships among species). We applied our model to longitudinal human microbiome data, and found that for the individuals we analyzed, the human microbiome generally follows the underdispersion (i.e., nepotism) hypothesis. Exceptions were oral communities and the fecal communities of two infants that had undergone heavy antibiotic treatment. None of the datasets we analyzed showed statistically significant phylogenetic overdispersion.}, }
@article {pmid32075244, year = {2020}, author = {Benedetti, F and Cocchi, F and Latinovic, OS and Curreli, S and Krishnan, S and Munawwar, A and Gallo, RC and Zella, D}, title = {Role of Mycoplasma Chaperone DnaK in Cellular Transformation.}, journal = {International journal of molecular sciences}, volume = {21}, number = {4}, pages = {}, pmid = {32075244}, issn = {1422-0067}, mesh = {Apoptosis/genetics ; Cell Transformation, Neoplastic/genetics ; DNA Damage/genetics ; DNA Repair/genetics ; Humans ; Inflammation/*genetics/microbiology/pathology ; Molecular Chaperones/*genetics ; Mycoplasma/*genetics/pathogenicity ; Mycoplasma Infections/*genetics/microbiology ; Neoplasms/*genetics/pathology ; Poly (ADP-Ribose) Polymerase-1/genetics ; Tumor Suppressor Protein p53/genetics ; Ubiquitin Thiolesterase/genetics ; }, abstract = {Studies of the human microbiome have elucidated an array of complex interactions between prokaryotes and their hosts. However, precise bacterial pathogen-cancer relationships remain largely elusive, although several bacteria, particularly those establishing persistent intra-cellular infections, like mycoplasmas, can alter host cell cycles, affect apoptotic pathways, and stimulate the production of inflammatory substances linked to DNA damage, thus potentially promoting abnormal cell growth and transformation. Consistent with this idea, in vivo experiments in several chemically induced or genetically deficient mouse models showed that germ-free conditions reduce colonic tumor formation. We demonstrate that mycoplasma DnaK, a chaperone protein belonging to the Heath shock protein (Hsp)-70 family, binds Poly-(ADP-ribose) Polymerase (PARP)-1, a protein that plays a critical role in the pathways involved in recognition of DNA damage and repair, and reduces its catalytic activity. It also binds USP10, a key p53 regulator, reducing p53 stability and anti-cancer functions. Finally, we showed that bystander, uninfected cells take up exogenous DnaK-suggesting a possible paracrine function in promoting cellular transformation, over and above direct mycoplasma infection. We propose that mycoplasmas, and perhaps certain other bacteria with closely related DnaK, may have oncogenic activity, mediated through the inhibition of DNA repair and p53 functions, and may be involved in the initiation of some cancers but not necessarily involved nor necessarily even be present in later stages.}, }
@article {pmid32073295, year = {2020}, author = {Swanson, KS and de Vos, WM and Martens, EC and Gilbert, JA and Menon, RS and Soto-Vaca, A and Hautvast, J and Meyer, PD and Borewicz, K and Vaughan, EE and Slavin, JL}, title = {Effect of fructans, prebiotics and fibres on the human gut microbiome assessed by 16S rRNA-based approaches: a review.}, journal = {Beneficial microbes}, volume = {11}, number = {2}, pages = {101-129}, doi = {10.3920/BM2019.0082}, pmid = {32073295}, issn = {1876-2891}, mesh = {*Diet ; *Dietary Fiber ; Feces/microbiology ; *Fructans ; Gastrointestinal Microbiome/*genetics ; Humans ; Phylogeny ; *Prebiotics ; RNA, Ribosomal, 16S/genetics ; }, abstract = {The inherent and diverse capacity of dietary fibres, nondigestible oligosaccharides (NDOs) and prebiotics to modify the gut microbiota and markedly influence health status of the host has attracted rising interest. Research and collective initiatives to determine the composition and diversity of the human gut microbiota have increased over the past decade due to great advances in high-throughput technologies, particularly the 16S ribosomal RNA (rRNA) sequencing. Here we reviewed the application of 16S rRNA-based molecular technologies, both community wide (sequencing and phylogenetic microarrays) and targeted methodologies (quantitative PCR, fluorescent in situ hybridisation) to study the effect of chicory inulin-type fructans, NDOs and specific added fibres, such as resistant starches, on the human intestinal microbiota. Overall, such technologies facilitated the monitoring of microbiota shifts due to prebiotic/fibre consumption, though there are limited community-wide sequencing studies so far. Molecular studies confirmed the selective bifidogenic effect of fructans and galactooligosaccharides (GOS) in human intervention studies. Fructans only occasionally decreased relative abundance of Bacteroidetes or stimulated other groups. The sequencing studies for various resistant starches, polydextrose and beta-glucan showed broader effects with more and different types of gut microbial species being enhanced, often including phylotypes of Ruminococcaceae. There was substantial variation in terms of magnitude of response and in individual responses to a specific fibre or NDO which may be due to numerous factors, such as initial presence and relative abundance of a microbial type, diet, genetics of the host, and intervention parameters, such as intervention duration and fibre dose. The field will clearly benefit from a more systematic approach that will support defining the impact of prebiotics and fibres on the gut microbiome, identify biomarkers that link gut microbes to health, and address the personalised response of an individual's microbiota to prebiotics and dietary fibres.}, }
@article {pmid32066625, year = {2020}, author = {Ghosh, TS and Rampelli, S and Jeffery, IB and Santoro, A and Neto, M and Capri, M and Giampieri, E and Jennings, A and Candela, M and Turroni, S and Zoetendal, EG and Hermes, GDA and Elodie, C and Meunier, N and Brugere, CM and Pujos-Guillot, E and Berendsen, AM and De Groot, LCPGM and Feskins, EJM and Kaluza, J and Pietruszka, B and Bielak, MJ and Comte, B and Maijo-Ferre, M and Nicoletti, C and De Vos, WM and Fairweather-Tait, S and Cassidy, A and Brigidi, P and Franceschi, C and O'Toole, PW}, title = {Mediterranean diet intervention alters the gut microbiome in older people reducing frailty and improving health status: the NU-AGE 1-year dietary intervention across five European countries.}, journal = {Gut}, volume = {69}, number = {7}, pages = {1218-1228}, pmid = {32066625}, issn = {1468-3288}, mesh = {Aged ; *Diet, Mediterranean ; Europe ; Female ; Frailty/diet therapy/*prevention &amp; control ; *Gastrointestinal Microbiome/genetics ; Health Status ; Humans ; Male ; Patient Compliance ; RNA, Ribosomal, 16S/genetics ; Single-Blind Method ; }, abstract = {OBJECTIVE: Ageing is accompanied by deterioration of multiple bodily functions and inflammation, which collectively contribute to frailty. We and others have shown that frailty co-varies with alterations in the gut microbiota in a manner accelerated by consumption of a restricted diversity diet. The Mediterranean diet (MedDiet) is associated with health. In the NU-AGE project, we investigated if a 1-year MedDiet intervention could alter the gut microbiota and reduce frailty.<br><br>DESIGN: We profiled the gut microbiota in 612 non-frail or pre-frail subjects across five European countries (UK, France, Netherlands, Italy and Poland) before and after the administration of a 12-month long MedDiet intervention tailored to elderly subjects (NU-AGE diet).<br><br>RESULTS: Adherence to the diet was associated with specific microbiome alterations. Taxa enriched by adherence to the diet were positively associated with several markers of lower frailty and improved cognitive function, and negatively associated with inflammatory markers including C-reactive protein and interleukin-17. Analysis of the inferred microbial metabolite profiles indicated that the diet-modulated microbiome change was associated with an increase in short/branch chained fatty acid production and lower production of secondary bile acids, p-cresols, ethanol and carbon dioxide. Microbiome ecosystem network analysis showed that the bacterial taxa that responded positively to the MedDiet intervention occupy keystone interaction positions, whereas frailty-associated taxa are peripheral in the networks.<br><br>CONCLUSION: Collectively, our findings support the feasibility of improving the habitual diet to modulate the gut microbiota which in turn has the potential to promote healthier ageing.}, }
@article {pmid32065252, year = {2020}, author = {Peñalver Bernabé, B and Maki, PM and Dowty, SM and Salas, M and Cralle, L and Shah, Z and Gilbert, JA}, title = {Precision medicine in perinatal depression in light of the human microbiome.}, journal = {Psychopharmacology}, volume = {237}, number = {4}, pages = {915-941}, pmid = {32065252}, issn = {1432-2072}, support = {Arnold O Beckman Postdoctoral Award//Arnold and Mabel Beckman Foundation (US)/ ; }, mesh = {Brain/metabolism ; Depressive Disorder, Major/metabolism/psychology/*therapy ; Female ; Gastrointestinal Microbiome/*physiology ; Humans ; Infant ; Microbiota/physiology ; Postpartum Period/metabolism/psychology ; Precision Medicine/*methods/psychology ; Pregnancy ; Pregnancy Complications/metabolism/psychology/*therapy ; }, abstract = {Perinatal depression is the most common complication of pregnancy and affects the mother, fetus, and infant. Recent preclinical studies and a limited number of clinical studies have suggested an influence of the gut microbiome on the onset and course of mental health disorders. In this review, we examine the current state of knowledge regarding genetics, epigenetics, heritability, and neuro-immuno-endocrine systems biology in perinatal mood disorders, with a particular focus on the interaction between these factors and the gut microbiome, which is mediated via the gut-brain axis. We also provide an overview of experimental and analytical methods that are currently available to researchers interested in elucidating the influence of the gut microbiome on mental health disorders during pregnancy and postpartum.}, }
@article {pmid32060812, year = {2020}, author = {Wilson, AS and Koller, KR and Ramaboli, MC and Nesengani, LT and Ocvirk, S and Chen, C and Flanagan, CA and Sapp, FR and Merritt, ZT and Bhatti, F and Thomas, TK and O'Keefe, SJD}, title = {Diet and the Human Gut Microbiome: An International Review.}, journal = {Digestive diseases and sciences}, volume = {65}, number = {3}, pages = {723-740}, pmid = {32060812}, issn = {1573-2568}, support = {R01 CA135379/CA/NCI NIH HHS/United States ; R01 CA204403/CA/NCI NIH HHS/United States ; }, mesh = {*Diet/trends ; Diet, Western/adverse effects ; Dietary Fiber/*microbiology ; Gastrointestinal Microbiome/*physiology ; Humans ; *Internationality ; Milk, Human/*microbiology/physiology ; }, abstract = {This review summarizes the key results of recently published studies on the effects of dietary change and nutritional intervention on the human microbiome from around the world, focusing on the USA, Canada, Europe, Asia, and Africa. It first explores mechanisms that might explain the ability of fiber-rich foods to suppress the incidence and mortality from westernized diseases, notably cancers of the colon, breast, liver, cardiovascular, infectious, and respiratory diseases, diabetes, and obesity (O'Keefe in Lancet Gastroenterol Hepatol 4(12):984-996, 2019; Am J Clin Nutr 110:265-266, 2019). It summarizes studies from Africa which suggest that disturbance of the colonic microbiome may exacerbate chronic malnutrition and growth failure in impoverished communities and highlights the importance of breast feeding. The American section discusses the role of the microbiome in the swelling population of patients with obesity and type 2 diabetes and examines the effects of race, ethnicity, geography, and climate on microbial diversity and metabolism. The studies from Europe and Asia extoll the benefits of whole foods and plant-based diets. The Asian studies examine the worrying changes from low-fat, high-carbohydrate diets to high-fat, low-carbohydrate ones and the increasing appearance of westernized diseases as in Africa and documents the ability of high-fiber traditional Chinese diets to reverse type 2 diabetes and control weight loss. In conclusion, most of the studies reviewed demonstrate clear changes in microbe abundances and in the production of fermentation products, such as short-chain fatty acids and phytochemicals following dietary change, but the significance of the microbiota changes to human health, with the possible exception of the stimulation of butyrogenic taxa by fiber-rich foods, is generally implied and not measured. Further studies are needed to determine how these changes in microbiota composition and metabolism can improve our health and be used to prevent and treat disease.}, }
@article {pmid32055399, year = {2020}, author = {Garza, DR and Taddese, R and Wirbel, J and Zeller, G and Boleij, A and Huynen, MA and Dutilh, BE}, title = {Metabolic models predict bacterial passengers in colorectal cancer.}, journal = {Cancer &amp; metabolism}, volume = {8}, number = {}, pages = {3}, pmid = {32055399}, issn = {2049-3002}, abstract = {BACKGROUND: Colorectal cancer (CRC) is a complex multifactorial disease. Increasing evidence suggests that the microbiome is involved in different stages of CRC initiation and progression. Beyond specific pro-oncogenic mechanisms found in pathogens, metagenomic studies indicate the existence of a microbiome signature, where particular bacterial taxa are enriched in the metagenomes of CRC patients. Here, we investigate to what extent the abundance of bacterial taxa in CRC metagenomes can be explained by the growth advantage resulting from the presence of specific CRC metabolites in the tumor microenvironment.<br><br>METHODS: We composed lists of metabolites and bacteria that are enriched on CRC samples by reviewing metabolomics experimental literature and integrating data from metagenomic case-control studies. We computationally evaluated the growth effect of CRC enriched metabolites on over 1500 genome-based metabolic models of human microbiome bacteria. We integrated the metabolomics data and the mechanistic models by using scores that quantify the response of bacterial biomass production to CRC-enriched metabolites and used these scores to rank bacteria as potential CRC passengers.<br><br>RESULTS: We found that metabolic networks of bacteria that are significantly enriched in CRC metagenomic samples either depend on metabolites that are more abundant in CRC samples or specifically benefit from these metabolites for biomass production. This suggests that metabolic alterations in the cancer environment are a major component shaping the CRC microbiome.<br><br>CONCLUSION: Here, we show with in sillico models that supplementing the intestinal environment with CRC metabolites specifically predicts the outgrowth of CRC-associated bacteria. We thus mechanistically explain why a range of CRC passenger bacteria are associated with CRC, enhancing our understanding of this disease. Our methods are applicable to other microbial communities, since it allows the systematic investigation of how shifts in the microbiome can be explained from changes in the metabolome.}, }
@article {pmid32054471, year = {2020}, author = {Nazareth, R and Chasqueira, MJ and Rodrigues, ML and Paulino, C and Conceição, C and Lêdo, L and Segura, &#xda; and Santos, M and Messias, A and Póvoa, P and Paixão, P}, title = {Respiratory viruses in mechanically ventilated patients: a pilot study.}, journal = {BMC pulmonary medicine}, volume = {20}, number = {1}, pages = {39}, pmid = {32054471}, issn = {1471-2466}, mesh = {Adult ; Aged ; Aged, 80 and over ; Cohort Studies ; Female ; Humans ; Male ; Middle Aged ; Pilot Projects ; *Respiration, Artificial ; Respiratory Insufficiency/*therapy/*virology ; Respiratory Tract Infections/*complications/diagnosis/therapy ; Virus Diseases/*complications/*diagnosis/virology ; Young Adult ; }, abstract = {BACKGROUND: Respiratory virome is an integral part of the human microbiome and its characterization may contribute to a better understanding of the changes that arise in the disease and, consequently, influence the approach and treatment of patients with acute lower respiratory infections. The aim of this study was to evaluate the presence of respiratory viruses in the lower airways of individuals undergoing invasive mechanical ventilation, with and without acute lower respiratory infection (respectively WRI and WORI groups).<br><br>METHODS: We studied 44 mini-bronchoalveolar lavage samples (collected with a double catheter, Combicath&#xae; kit) from patients with mean age in the seventh decade, 20 from WORI group and 24 from WRI group, who were hospitalized for acute respiratory failure in Intensive Care Units of two hospitals in the Lisbon area. Real-time PCR was applied to verify analyse the presence of 15 common respiratory viruses (adenovirus, human bocavirus, influenza virus A and B, repiratory syncytial virus, human parainfluenza virus types 1, 2, 3 and 4, human enterovirus, human rhinovirus, human metapneumovirus, human coronavirus group 1 (229E, NL63) and 2 (OC43, HKU1).<br><br>RESULTS: Respiratory viruses were detected in six of the 20 patients in the WORI group: influenza AH3 (n&#x2009;=&#x2009;2), parainfluenza virus 1/3 (n&#x2009;=&#x2009;2), human rhinovirus (n&#x2009;=&#x2009;2), respiratory syncytial virus (n&#x2009;=&#x2009;1) and human metapneumovirus (n&#x2009;=&#x2009;1). In the WRI group, respiratory viruses were detected in 12 of the 24 patients: influenza AH3 (n&#x2009;=&#x2009;3), human rhinovirus (n&#x2009;=&#x2009;3), respiratory syncytial virus (n&#x2009;=&#x2009;3), human metapneumovirus (n&#x2009;=&#x2009;3), human bocavirus (n&#x2009;=&#x2009;2) and human enterovirus (n&#x2009;=&#x2009;1). Simultaneous detection of two viruses was recorded in two samples in both groups.<br><br>CONCLUSIONS: The results of this study suggest the presence of common respiratory viruses in the lower respiratory tract without causing symptomatic infection, even in carefully collected lower samples. This may have important implications on the interpretation of the results on the diagnostic setting.}, }
@article {pmid32040665, year = {2020}, author = {Engstrand, L and Graham, DY}, title = {Microbiome and Gastric Cancer.}, journal = {Digestive diseases and sciences}, volume = {65}, number = {3}, pages = {865-873}, pmid = {32040665}, issn = {1573-2568}, support = {P30 DK056338/DK/NIDDK NIH HHS/United States ; }, mesh = {Gastric Mucosa/*microbiology/physiopathology ; Gastrointestinal Microbiome/*physiology ; Helicobacter pylori/isolation &amp; purification/*physiology ; Host Microbial Interactions/physiology ; Humans ; Stomach Neoplasms/*microbiology/pathology/physiopathology ; }, abstract = {The late 1800s Louis Pasteur and Robert Koch introduced and popularized the germ theory of disease. At that time, gastric cancer was the most common cause of cancer deaths in most countries making the stomach an early site of microbial research with a focus on gastric luminal and mucosal bacteria and the role of Boas-Oppler bacillus (Lactobacillus) in the diagnosis of gastric cancer. In the 1970s, the research focus evolved to studies of the gastric microbiome in the production of nitrosamines and included development of the Correa cascade. Interest in nitrosamine production peaked in the late 1980s and was replaced by studies of the newly described Helicobacter pylori and studies of its role in gastritis, gastric atrophy, and gastric cancer. The last decade has witnessed a rebirth in interest in the gastric microbiota as part of worldwide interest in the human microbiome. Although fungi were prominent in the studies of gastric microbiology in the nineteenth century, their potential role in disease pathogenesis has yet to be addressed using modern techniques. Overall, current studies of the gastric bacterial microbiome do not provide convincing evidence to expand the role of the gastric microbiome in cancer pathogenesis beyond what is directly attributable to the oncogenic potential of H. pylori and its role in persisting acute-on-chronic inflammation.}, }
@article {pmid32040250, year = {2020}, author = {Guo, XY and Liu, XJ and Hao, JY}, title = {Gut microbiota in ulcerative colitis: insights on pathogenesis and treatment.}, journal = {Journal of digestive diseases}, volume = {21}, number = {3}, pages = {147-159}, doi = {10.1111/1751-2980.12849}, pmid = {32040250}, issn = {1751-2980}, support = {81300294//Youth Program of National Natural Science Foundation of China/ ; XXT11//Project of Digestive Medical Coordinated Development Center of Beijing Hospitals Authority/ ; PX2018011//Incubation Program Project of Beijing Municipal Administration of Hospitals of China/ ; 7192072//Beijing Natural Science Foundation/ ; }, mesh = {Colitis, Ulcerative/immunology/microbiology/*therapy ; Dysbiosis/immunology/microbiology/*therapy ; Fecal Microbiota Transplantation/*methods ; Gastrointestinal Microbiome/*immunology ; Humans ; Immunity, Innate ; Intestinal Mucosa/immunology/*microbiology ; Treatment Outcome ; }, abstract = {Gut microbiota constitute the largest reservoir of the human microbiome and are an abundant and stable ecosystem-based on its diversity, complexity, redundancy, and host interactions This ecosystem is indispensable for human development and health. The integrity of the intestinal mucosal barrier depends on its interactions with gut microbiota. The commensal bacterial community is implicated in the pathogenesis of inflammatory bowel disease (IBD), including ulcerative colitis (UC). The dysbiosis of microbes is characterized by reduced biodiversity, abnormal composition of gut microbiota, altered spatial distribution, as well as interactions among microbiota, between different strains of microbiota, and with the host. The defects in microecology, with the related metabolic pathways and molecular mechanisms, play a critical role in the innate immunity of the intestinal mucosa in UC. Fecal microbiota transplantation (FMT) has been used to treat many diseases related to gut microbiota, with the most promising outcome reported in antibiotic-associated diarrhea, followed by IBD. This review evaluated the results of various reports of FMT in UC. The efficacy of FMT remains highly controversial, and needs to be regularized by integrated management, standardization of procedures, and individualization of treatment.}, }
@article {pmid32037278, year = {2020}, author = {Rao, BC and Lou, JM and Wang, WJ and Li, A and Cui, GY and Yu, ZJ and Ren, ZG}, title = {Human microbiome is a diagnostic biomarker in hepatocellular carcinoma.}, journal = {Hepatobiliary &amp; pancreatic diseases international : HBPD INT}, volume = {19}, number = {2}, pages = {109-115}, doi = {10.1016/j.hbpd.2020.01.003}, pmid = {32037278}, issn = {1499-3872}, mesh = {Biomarkers ; Carcinoma, Hepatocellular/*diagnosis ; *Gastrointestinal Microbiome ; Hepatitis, Chronic/*microbiology/virology ; Humans ; Liver Cirrhosis/microbiology ; Liver Diseases, Alcoholic/microbiology ; Liver Neoplasms/*diagnosis ; Mouth/*microbiology ; Non-alcoholic Fatty Liver Disease/microbiology ; Precancerous Conditions/*microbiology ; }, abstract = {BACKGROUND: Hepatocellular carcinoma (HCC) is the third leading cause of cancer mortality worldwide. Increasing evidence indicates a close relationship between HCC and the human microbiota. Herein, we reviewed the important potential of the human microbiota as a diagnostic biomarker of HCC.<br><br>DATA SOURCES: Several innovative studies have investigated the characteristics of the gut and oral microbiomes in patients with HCC and proposed that the human microbiome has the potential to be a diagnostic biomarker of HCC. Literature from February 1999 to February 2019 was searched in the PubMed database using the keywords "microbiota" or "microbiome" or "microbe" and "liver cancer" or "hepatocellular carcinoma", and the results of clinical and experimental studies were analyzed.<br><br>RESULTS: Specific changes occur in the human microbiome of patients with HCC. Moreover, the gut microbiome and oral microbiome can be used as non-invasive diagnostic biomarkers for HCC. Furthermore, they also have certain diagnostic potential for precancerous diseases of HCC. The diagnostic potential of the blood microbiota and ascites microbiota in HCC will be gradually discovered in the future.<br><br>CONCLUSIONS: The human microbiome is valuable to the diagnosis of HCC and provides a novel strategy for targeted therapy of HCC. The human microbiome may be widely used in the diagnosis, treatment and prognosis for multiple system diseases or cancers in the future.}, }
@article {pmid32023941, year = {2020}, author = {Chowdhury, S and Fong, SS}, title = {Computational Modeling of the Human Microbiome.}, journal = {Microorganisms}, volume = {8}, number = {2}, pages = {}, pmid = {32023941}, issn = {2076-2607}, support = {U54HD080784//Office of Extramural Research, National Institutes of Health/ ; }, abstract = {The impact of microorganisms on human health has long been acknowledged and studied, but recent advances in research methodologies have enabled a new systems-level perspective on the collections of microorganisms associated with humans, the human microbiome. Large-scale collaborative efforts such as the NIH Human Microbiome Project have sought to kick-start research on the human microbiome by providing foundational information on microbial composition based upon specific sites across the human body. Here, we focus on the four main anatomical sites of the human microbiome: gut, oral, skin, and vaginal, and provide information on site-specific background, experimental data, and computational modeling. Each of the site-specific microbiomes has unique organisms and phenomena associated with them; there are also high-level commonalities. By providing an overview of different human microbiome sites, we hope to provide a perspective where detailed, site-specific research is needed to understand causal phenomena that impact human health, but there is equally a need for more generalized methodology improvements that would benefit all human microbiome research.}, }
@article {pmid32023871, year = {2020}, author = {Panyukov, VV and Kiselev, SS and Ozoline, ON}, title = {Unique k-mers as Strain-Specific Barcodes for Phylogenetic Analysis and Natural Microbiome Profiling.}, journal = {International journal of molecular sciences}, volume = {21}, number = {3}, pages = {}, pmid = {32023871}, issn = {1422-0067}, support = {18-14-00348//Russian Science Foundation/ ; 18-07-00899//&#x420;&#x43e;&#x441;&#x441;&#x438;&#x439;&#x441;&#x43a;&#x438;&#x439; &#x424;&#x43e;&#x43d;&#x434; &#x424;&#x443;&#x43d;&#x434;&#x430;&#x43c;&#x435;&#x43d;&#x442;&#x430;&#x43b;&#x44c;&#x43d;&#x44b;&#x445; &#x418;&#x441;&#x441;&#x43b;&#x435;&#x434;&#x43e;&#x432;&#x430;&#x43d;&#x438;&#x439; (&#x420;&#x424;&#x424;&#x418;)/ ; }, mesh = {Algorithms ; Case-Control Studies ; Computational Biology ; Crohn Disease/*genetics/microbiology ; DNA Barcoding, Taxonomic/*methods ; Escherichia coli/classification/*genetics/isolation &amp; purification ; Escherichia coli Infections/*genetics/microbiology ; *Genes, Bacterial ; *Genome, Bacterial ; Humans ; Metagenome ; *Microbiota ; }, abstract = {The need for a comparative analysis of natural metagenomes stimulated the development of new methods for their taxonomic profiling. Alignment-free approaches based on the search for marker k-mers turned out to be capable of identifying not only species, but also strains of microorganisms with known genomes. Here, we evaluated the ability of genus-specific k-mers to distinguish eight phylogroups of Escherichia coli (A, B1, C, E, D, F, G, B2) and assessed the presence of their unique 22-mers in clinical samples from microbiomes of four healthy people and four patients with Crohn's disease. We found that a phylogenetic tree inferred from the pairwise distance matrix for unique 18-mers and 22-mers of 124 genomes was fully consistent with the topology of the tree, obtained with concatenated aligned sequences of orthologous genes. Therefore, we propose strain-specific "barcodes" for rapid phylotyping. Using unique 22-mers for taxonomic analysis, we detected microbes of all groups in human microbiomes; however, their presence in the five samples was significantly different. Pointing to the intraspecies heterogeneity of E. coli in the natural microflora, this also indicates the feasibility of further studies of the role of this heterogeneity in maintaining population homeostasis.}, }
@article {pmid32014010, year = {2020}, author = {Botticelli, A and Vernocchi, P and Marini, F and Quagliariello, A and Cerbelli, B and Reddel, S and Del Chierico, F and Di Pietro, F and Giusti, R and Tomassini, A and Giampaoli, O and Miccheli, A and Zizzari, IG and Nuti, M and Putignani, L and Marchetti, P}, title = {Gut metabolomics profiling of non-small cell lung cancer (NSCLC) patients under immunotherapy treatment.}, journal = {Journal of translational medicine}, volume = {18}, number = {1}, pages = {49}, pmid = {32014010}, issn = {1479-5876}, mesh = {*Carcinoma, Non-Small-Cell Lung/drug therapy ; *Gastrointestinal Microbiome ; Humans ; Immunotherapy ; *Lung Neoplasms/drug therapy ; Metabolomics ; }, abstract = {BACKGROUND: Despite the efficacy of immune checkpoint inhibitors (ICIs) only the 20-30% of treated patients present long term benefits. The metabolic changes occurring in the gut microbiota metabolome are herein proposed as a factor potentially influencing the response to immunotherapy.<br><br>METHODS: The metabolomic profiling of gut microbiota was characterized in 11 patients affected by non-small cell lung cancer (NSCLC) treated with nivolumab in second-line treatment with anti-PD-1 nivolumab. The metabolomics analyses were performed by GC-MS/SPME and [1]H-NMR in order to detect volatile and non-volatile metabolites. Metabolomic data were processed by statistical profiling and chemometric analyses.<br><br>RESULTS: Four out of 11 patients (36%) presented early progression, while the remaining 7 out of 11 (64%) presented disease progression after 12&#xa0;months. 2-Pentanone (ketone) and tridecane (alkane) were significantly associated with early progression, and on the contrary short chain fatty acids (SCFAs) (i.e., propionate, butyrate), lysine and nicotinic acid were significantly associated with long-term beneficial effects.<br><br>CONCLUSIONS: Our preliminary data suggest a significant role of gut microbiota metabolic pathways in affecting response to immunotherapy. The metabolic approach could be a promising strategy to contribute to the personalized management of cancer patients by the identification of microbiota-linked "indicators" of early progressor and long responder patients.}, }
@article {pmid32011231, year = {2020}, author = {Cepko, LCS and Garling, EE and Dinsdale, MJ and Scott, WP and Bandy, L and Nice, T and Faber-Hammond, J and Mellies, JL}, title = {Myoviridae phage PDX kills enteroaggregative Escherichia coli without human microbiome dysbiosis.}, journal = {Journal of medical microbiology}, volume = {69}, number = {2}, pages = {309-323}, pmid = {32011231}, issn = {1473-5644}, mesh = {Animals ; Bacteria/classification/genetics/isolation &amp; purification ; Bacteriophages/classification/genetics/isolation &amp; purification/*physiology ; Dysbiosis/microbiology ; Escherichia coli/physiology/*virology ; Escherichia coli Infections/microbiology/*therapy ; Female ; Humans ; Male ; Mice ; Mice, Inbred C57BL ; Microbiota ; Myoviridae/classification/genetics/isolation &amp; purification/*physiology ; Phylogeny ; }, abstract = {Introduction. Bacteriophage therapy can be developed to target emerging diarrhoeal pathogens, but doing so in the absence of microbiome disruption, which occurs with antibiotic treatment, has not been established.Aim. Identify a therapeutic bacteriophage that kills diarrhoeagenic enteroaggregative Escherichia coli (EAEC) while leaving the human microbiome intact.Methodology. Phages from wastewater in Portland, OR, USA were screened for bacteriolytic activity by overlay assay. One isolated phage, PDX, was classified by electron microscopy and genome sequencing. A mouse model of infection determined whether the phage was therapeutic against EAEC. 16S metagenomic analysis of anaerobic cultures determined whether a normal human microbiome was altered by treatment.Results. Escherichia virus PDX, a member of the strictly lytic family Myoviridae, killed a case-associated EAEC isolate from a child in rural Tennessee in a dose-dependent manner, and killed EAEC isolates from Columbian children. A single dose of PDX (multiplicity of infection: 100) 1 day post-infection reduced EAEC recovered from mouse faeces. PDX also killed EAEC when cultured anaerobically in the presence of human faecal bacteria. While the addition of EAEC reduced the β-diversity of the human microbiota, that of the cultures with either faeces alone, faeces with EAEC and PDX, or with just PDX phage was not different statistically.Conclusion. PDX killed EAEC isolate EN1E-0007 in vivo and in vitro, while not altering the diversity of normal human microbiota in anaerobic culture, and thus could be part of an effective therapy for children in developing countries and those suffering from EAEC-mediated traveller's diarrhoea without causing dysbiosis.}, }
@article {pmid32010645, year = {2019}, author = {Zhang, L and Liu, Y and Zheng, HJ and Zhang, CP}, title = {The Oral Microbiota May Have Influence on Oral Cancer.}, journal = {Frontiers in cellular and infection microbiology}, volume = {9}, number = {}, pages = {476}, pmid = {32010645}, issn = {2235-2988}, mesh = {Bacteria/*classification/genetics/isolation &amp; purification ; Carcinoma, Squamous Cell/*etiology/*microbiology ; DNA, Ribosomal/genetics ; Female ; Fusobacterium nucleatum ; Humans ; Lipopolysaccharides ; Male ; Microbiota/*physiology ; Middle Aged ; Mouth/*microbiology ; Mouth Mucosa/microbiology ; Peptostreptococcus ; Prevotella intermedia ; RNA, Ribosomal, 16S/genetics ; }, abstract = {The oral microbiota plays an important role in the human microbiome and human health, and imbalances between microbes and their hosts can lead to oral and systemic diseases and chronic inflammation, which is usually caused by bacteria and contributes to cancer. There may be a relationship between oral bacteria and oral squamous cell carcinoma (OSCC); however, this relationship has not been thoroughly characterized. Therefore, in this study, we compared the microbiota compositions between tumor sites and opposite normal tissues in buccal mucosal of 50 patients with OSCC using the 16S rDNA sequencing. Richness and diversity of bacteria were significantly higher in tumor sites than in the control tissues. Cancer tissues were enriched in six families (Prevotellaceae, Fusobacteriaceae, Flavobacteriaceae, Lachnospiraceae, Peptostreptococcaceae, and Campylobacteraceae) and 13 genera, including Fusobacterium, Alloprevotella and Porphyromonas. At the species level, the abundances of Fusobacterium nucleatum, Prevotella intermedia, Aggregatibacter segnis, Capnocytophaga leadbetteri, Peptostreptococcus stomatis, and another five species were significantly increased, suggesting a potential association between these bacteria and OSCC. Furthermore, the functional prediction revealed that genes involved in bacterial chemotaxis, flagellar assembly and lipopolysaccharide (LPS) biosynthesis which are associated with various pathological processes, were significantly increased in the OSCC group. Overall, oral bacterial profiles showed significant difference between cancer sites and normal tissue of OSCC patients, which might be onsidered diagnostic markers and treatment targets. Our study has been registered in the Chinese clinical trial registry (ChiCTR1900025253, http://www.chictr.org.cn/index.aspx).}, }
@article {pmid31996419, year = {2020}, author = {Ghannam, RB and Schaerer, LG and Butler, TM and Techtmann, SM}, title = {Biogeographic Patterns in Members of Globally Distributed and Dominant Taxa Found in Port Microbial Communities.}, journal = {mSphere}, volume = {5}, number = {1}, pages = {}, pmid = {31996419}, issn = {2379-5042}, mesh = {Actinobacteria/*classification ; Asia ; Bacteroidetes/*classification ; *Biodiversity ; Cyanobacteria/*classification ; DNA, Bacterial/genetics ; Europe ; Fresh Water/microbiology ; Machine Learning ; Microbiota ; Phylogeography ; Proteobacteria/*classification ; RNA, Ribosomal, 16S/genetics ; Seawater/microbiology ; Ships ; United States ; *Water Microbiology ; }, abstract = {We conducted a global characterization of the microbial communities of shipping ports to serve as a novel system to investigate microbial biogeography. The community structures of port microbes from marine and freshwater habitats house relatively similar phyla, despite spanning large spatial scales. As part of this project, we collected 1,218 surface water samples from 604 locations across eight countries and three continents to catalogue a total of 20 shipping ports distributed across the East and West Coast of the United States, Europe, and Asia to represent the largest study of port-associated microbial communities to date. Here, we demonstrated the utility of machine learning to leverage this robust system to characterize microbial biogeography by identifying trends in biodiversity across broad spatial scales. We found that for geographic locations sharing similar environmental conditions, subpopulations from the dominant phyla of these habitats (Actinobacteria, Bacteroidetes, Cyanobacteria, and Proteobacteria) can be used to differentiate 20 geographic locations distributed globally. These results suggest that despite the overwhelming diversity within microbial communities, members of the most abundant and ubiquitous microbial groups in the system can be used to differentiate a geospatial location across global spatial scales. Our study provides insight into how microbes are dispersed spatially and robust methods whereby we can interrogate microbial biogeography.IMPORTANCE Microbes are ubiquitous throughout the world and are highly diverse. Characterizing the extent of variation in the microbial diversity across large geographic spatial scales is a challenge yet can reveal a lot about what biogeography can tell us about microbial populations and their behavior. Machine learning approaches have been used mostly to examine the human microbiome and, to some extent, microbial communities from the environment. Here, we display how supervised machine learning approaches can be useful to understand microbial biodiversity and biogeography using microbes from globally distributed shipping ports. Our findings indicate that the members of globally dominant phyla are important for differentiating locations, which reduces the reliance on rare taxa to probe geography. Further, this study displays how global biogeographic patterning of aquatic microbial communities (and other systems) can be assessed through populations of the highly abundant and ubiquitous taxa that dominant the system.}, }
@article {pmid31993418, year = {2019}, author = {Kang, W and Sun, T and Tang, D and Zhou, J and Feng, Q}, title = {Time-Course Transcriptome Analysis of Gingiva-Derived Mesenchymal Stem Cells Reveals That Fusobacterium nucleatum Triggers Oncogene Expression in the Process of Cell Differentiation.}, journal = {Frontiers in cell and developmental biology}, volume = {7}, number = {}, pages = {359}, pmid = {31993418}, issn = {2296-634X}, abstract = {Fusobacterium nucleatum has pathogenic effects on oral squamous cell carcinoma and colon cancer, while the effects of continuously altered gene expression in normal human cells, as induced by persistent exposure to F. nucleatum, remain unclear. In this study, a microarray Significant Profiles (maSigPro) analysis was used to obtain the transcriptome profile of gingiva-derived mesenchymal stem cells (GMSCs) stimulated by F. nucleatum for 3, 7, 14, and 21 day, and the results revealed 790 (nine clusters) differentially expressed genes (DEGs), which were significantly enriched in cell adherens junctions and cancer-related pathways. On the basis of a short time-series expression miner (STEM) analysis, all the expressed genes in the GMSCs were grouped into 50 clusters according to dynamic gene expression patterns, and the expression levels of three gene clusters in the F. nucleatum-treated GMSCs were significantly different than the predicted values. Among the 790 DEGs, 50 tumor-associated genes (TAGs; such as L3MBTL4, CD163, CCCND2, CADM1, BCL7A, and IGF1) and five core dynamic DEGs (PLCG2, CHI3L2, L3MBTL4, SH2D2A, and NLRP3) were identified during F. nucleatum stimulation. Results from a GeneMANIA database analysis showed that PLCG2, CHI3L2, SH2D2A, and NLRP3 and 20 other proteins formed a complex network of which 12 genes were enriched in cancer-related pathways. Based on the five core dynamic DEGs, the related microRNAs (miRNAs) and transcription factors (TFs) were obtained from public resources, and an integrated network composed of the related TFs, miRNAs, and mRNAs was constructed. The results indicated that these genes were regulated by several miRNAs, such as miR-372-3p, miR-603, and miR-495-3p, and several TFs, including CREB3, GATA2, and SOX4. Our study suggests that long-term stimulation by F. nucleatum may trigger the expression of cancer-related genes in normal gingiva-derived stem cells.}, }
@article {pmid31991821, year = {2020}, author = {Simões-Silva, L and Araujo, R and Pestana, M and Soares-Silva, I and Sampaio-Maia, B}, title = {Peritoneal Microbiome in End-Stage Renal Disease Patients and the Impact of Peritoneal Dialysis Therapy.}, journal = {Microorganisms}, volume = {8}, number = {2}, pages = {}, pmid = {31991821}, issn = {2076-2607}, support = {Research Grant 2014 to ISS//European Society of Clinical Microbiology and Infectious Diseases/ ; SFRH/BPD/101016/2014//Funda&#xe7;&#xe3;o para a Ci&#xea;ncia e a Tecnologia/ ; POCI-01-0145-FEDER-029777//Funda&#xe7;&#xe3;o para a Ci&#xea;ncia e a Tecnologia/ ; PTDC/MEC-MCI/29777/2017//Funda&#xe7;&#xe3;o para a Ci&#xea;ncia e a Tecnologia/ ; UID/BIA/04050/2019//Funda&#xe7;&#xe3;o para a Ci&#xea;ncia e a Tecnologia/ ; }, abstract = {Factors influencing the occurrence of peritoneal dialysis (PD)-related infections are still far from fully understood. Recent studies described the existence of specific microbiomes in body sites previously considered microbiome-free, unravelling new microbial pathways in the human body. In the present study, we analyzed the peritoneum of end-stage kidney disease (ESKD) patients to determine if they harbored a specific microbiome and if it is altered in patients on PD therapy. We conducted a cross-sectional study where the peritoneal microbiomes from ESKD patients with intact peritoneal cavities (ESKD non-PD, n = 11) and ESKD patients undergoing PD therapy (ESKD PD, n = 9) were analyzed with a 16S rRNA approach. Peritoneal tissue of ESKD patients contained characteristically low-abundance microbiomes dominated by Proteobacteria, Firmicutes, Actinobacteria, and Bacteroidetes. Patients undergoing PD therapy presented lower species richness, with dominance by the Pseudomonadaceae and Prevotelaceae families. This study provides the first characterization of the peritoneal microbiome in ESKD patients, bringing new insight to the human microbiome. Additionally, PD therapy may induce changes in this unique microbiome. The clinical relevance of these observations should be further explored to uncover the role of the peritoneal microbiome as a key element in the onset or aggravation of infection in ESKD patients, especially those undergoing PD.}, }
@article {pmid31988008, year = {2020}, author = {Zhang, Y and Ying, X and He, Y and Jiang, L and Zhang, S and Bartra, SS and Plano, GV and Klena, JD and Skurnik, M and Chen, H and Cai, H and Chen, T}, title = {Invasiveness of the Yersinia pestis ail protein contributes to host dissemination in pneumonic and oral plague.}, journal = {Microbial pathogenesis}, volume = {141}, number = {}, pages = {103993}, doi = {10.1016/j.micpath.2020.103993}, pmid = {31988008}, issn = {1096-1208}, mesh = {Animals ; Bacterial Outer Membrane Proteins/*metabolism ; Bacterial Proteins/metabolism ; Disease Models, Animal ; Lung/microbiology ; Mice ; Mice, Inbred C57BL ; Mouth/microbiology ; Plague/*microbiology ; *Virulence ; Virulence Factors/*metabolism ; *Yersinia pestis/metabolism/pathogenicity ; }, abstract = {Yersinia pestis, a Gram-negative bacterium, is the etiologic agent of plague. A hallmark of Y. pestis infection is the organism's ability to rapidly disseminate through an animal host. Y. pestis expresses the outer membrane protein, Ail (Attachment invasion locus), which is associated with host invasion and serum resistance. However, whether Ail plays a role in host dissemination remains unclear. In this study, C57BL/6J mice were challenged with a defined Y. pestis strain, KimD27, or an isogenic ail-deleted mutant derived from KimD27 via metacarpal paw pad inoculation, nasal drops, orogastric infection, or tail vein injection to mimic bubonic, pneumonic, oral, or septicemic plague, respectively. Our results showed that ail-deleted Y. pestis KimD27 lost the ability to invade host cells, leading to failed host dissemination in the pneumonic and oral plague models but not in the bubonic or septicemic plague models, which do not require invasiveness. Therefore, this study demonstrated that whether Ail plays a role in Y. pestis pathogenesis depends on the infection route.}, }
@article {pmid31979276, year = {2020}, author = {Oduor, JMO and Kadija, E and Nyachieo, A and Mureithi, MW and Skurnik, M}, title = {Bioprospecting Staphylococcus Phages with Therapeutic and Bio-Control Potential.}, journal = {Viruses}, volume = {12}, number = {2}, pages = {}, pmid = {31979276}, issn = {1999-4915}, mesh = {Albania ; Biological Control Agents/*isolation &amp; purification ; *Bioprospecting ; Chloroform/pharmacology ; Ethanol/pharmacology ; Genome, Viral ; Genomics ; Host Specificity ; Hydrogen-Ion Concentration ; Phage Therapy ; Sequence Analysis, DNA ; Staphylococcal Infections/therapy ; Staphylococcus Phages/*classification/*physiology ; Staphylococcus aureus/*virology ; Temperature ; }, abstract = {Emergence of antibiotic-resistant bacteria is a serious threat to the public health. This is also true for Staphylococcus aureus and other staphylococci. Staphylococcus phages Stab20, Stab21, Stab22, and Stab23, were isolated in Albania. Based on genomic and phylogenetic analysis, they were classified to genus Kayvirus of the subfamily Twortvirinae. In this work, we describe the in-depth characterization of the phages that electron microscopy confirmed to be myoviruses. These phages showed tolerance to pH range of 5.4 to 9.4, to maximum UV radiation energy of 25 µJ/cm[2], to temperatures up to 45 °C, and to ethanol concentrations up to 25%, and complete resistance to chloroform. The adsorption rate constants of the phages ranged between 1.0 × 10[-9] mL/min and 4.7 × 10[-9] mL/min, and the burst size was from 42 to 130 plaque-forming units. The phages Stab20, 21, 22, and 23, originally isolated using Staphylococcusxylosus as a host, demonstrated varied host ranges among different Staphylococcus strains suggesting that they could be included in cocktail formulations for therapeutic or bio-control purpose. Phage particle proteomes, consisting on average of ca 60-70 gene products, revealed, in addition to straight-forward structural proteins, also the presence of enzymes such DNA polymerase, helicases, recombinases, exonucleases, and RNA ligase polymer. They are likely to be injected into the bacteria along with the genomic DNA to take over the host metabolism as soon as possible after infection.}, }
@article {pmid31977194, year = {2020}, author = {Chevrette, MG and Handelsman, J}, title = {From Metagenomes to Molecules: Innovations in Functional Metagenomics Unlock Hidden Chemistry in the Human Microbiome.}, journal = {Biochemistry}, volume = {59}, number = {6}, pages = {729-730}, doi = {10.1021/acs.biochem.0c00033}, pmid = {31977194}, issn = {1520-4995}, mesh = {Humans ; Metagenome ; *Metagenomics ; *Microbiota ; }, }
@article {pmid31975449, year = {2020}, author = {Megrian, D and Taib, N and Witwinowski, J and Beloin, C and Gribaldo, S}, title = {One or two membranes? Diderm Firmicutes challenge the Gram-positive/Gram-negative divide.}, journal = {Molecular microbiology}, volume = {113}, number = {3}, pages = {659-671}, doi = {10.1111/mmi.14469}, pmid = {31975449}, issn = {1365-2958}, mesh = {Bacteria/genetics/metabolism ; Biological Evolution ; Cell Membrane/*genetics/ultrastructure ; Cell Wall/genetics/ultrastructure ; Evolution, Molecular ; Firmicutes/classification/genetics ; Gram-Negative Bacteria/genetics/metabolism/*ultrastructure ; Gram-Positive Bacteria/genetics/metabolism/*ultrastructure ; Lipopolysaccharides ; Phylogeny ; }, abstract = {How, when and why the transition between cell envelopes with one membrane (Gram-positives or monoderms) and two (Gram-negative or diderms) occurred in Bacteria is a key unanswered question in evolutionary biology. Different hypotheses have been put forward, suggesting that either the monoderm or the diderm phenotype is ancestral. The existence of diderm members in the classically monoderm Firmicutes challenges the Gram-positive/Gram-negative divide and provides a great opportunity to tackle the issue. In this review, we present current knowledge on the diversity of bacterial cell envelopes, including these atypical Firmicutes. We discuss how phylogenomic analysis supports the hypothesis that the diderm cell envelope architecture is an ancestral character in the Firmicutes, and that the monoderm phenotype in this phylum arose multiple times independently by loss of the outer membrane. Given the overwhelming distribution of diderm phenotypes with respect to monoderm ones, this scenario likely extends to the ancestor of all bacteria. Finally, we discuss the recent development of genetic tools for Veillonella parvula, a diderm Firmicute member of the human microbiome, which indicates it as an emerging new experimental model to investigate fundamental aspects of the diderm/monoderm transition.}, }
@article {pmid31967708, year = {2020}, author = {Napoli, E and Siracusa, L and Ruberto, G}, title = {New Tricks for Old Guys: Recent Developments in the Chemistry, Biochemistry, Applications and Exploitation of Selected Species from the Lamiaceae Family.}, journal = {Chemistry &amp; biodiversity}, volume = {17}, number = {3}, pages = {e1900677}, doi = {10.1002/cbdv.201900677}, pmid = {31967708}, issn = {1612-1880}, mesh = {Humans ; Lamiaceae/*chemistry ; Oils, Volatile/*chemistry ; Phytochemicals/*chemistry ; Plants, Medicinal/*chemistry ; }, abstract = {Lamiaceae is one of the largest families of flowering plants comprising about 250 genera and over 7,000 species. Most of the plants of this family are aromatic and therefore important source of essential oils. Lamiaceae are widely used as culinary herbs and reported as medicinal plants in several folk traditions. In the Mediterranean area oregano, sage, rosemary, thyme and lavender stand out for geographical diffusion and variety of uses. The aim of this review is to provide recent data dealing with the phytochemical and pharmacological studies, and the more recent applications of the essential oils and the non-volatile phytocomplexes. This literature survey suggests how the deeper understanding of biomolecular processes in the health and food sectors as per as pest control bioremediation of cultural heritage, or interaction with human microbiome, fields, leads to the rediscovery and new potential applications of well-known plants.}, }
@article {pmid31964769, year = {2020}, author = {Jia, Z and Zhao, X and Liu, X and Zhao, L and Jia, Q and Shi, J and Xu, X and Hao, L and Xu, Z and Zhong, Q and Yu, K and Cui, S and Chen, H and Guo, J and Li, X and Han, Y and Song, X and Zhao, C and Bo, X and Tian, Y and Wang, W and Xie, G and Feng, Q and He, K}, title = {Impacts of the Plateau Environment on the Gut Microbiota and Blood Clinical Indexes in Han and Tibetan Individuals.}, journal = {mSystems}, volume = {5}, number = {1}, pages = {}, pmid = {31964769}, issn = {2379-5077}, abstract = {The intestinal microbiota is significantly affected by the external environment, but our understanding of the effects of extreme environments such as plateaus is far from adequate. In this study, we systematically analyzed the variation in the intestinal microbiota and 76 blood clinical indexes among 393 healthy adults with different plateau living durations (Han individuals with no plateau living, with plateau living for 4 to 6 days, with plateau living for >3 months, and who returned to the plain for 3 months, as well as plateau-living Tibetans). The results showed that the high-altitude environment rapidly (4 days) and continually (more than 3 months) shaped both the intestinal microbiota and clinical indexes of the Han population. With prolongation of plateau living, the general characteristics of the intestinal microbiota and clinical indexes of the Han population were increasingly similar to those of the Tibetan population. The intestinal microbiota of the Han population that returned to the plain area for 3 months still resembled that of the plateau-living Han population rather than that of the Han population on the plain. Moreover, clinical indexes such as blood glucose were significantly lower in the plateau groups than in the nonplateau groups, while the opposite result was obtained for testosterone. Interestingly, there were Tibetan-specific correlations between glucose levels and Succinivibrio and Sarcina abundance in the intestine. The results of this study suggest that a hypoxic environment could rapidly and lastingly affect both the human intestinal microbiota and blood clinical indexes, providing new insights for the study of plateau adaptability.IMPORTANCE The data presented in the present study demonstrate that the hypoxic plateau environment has a profound impact on the gut microbiota and blood clinical indexes in Han and Tibetan individuals. The plateau-changed signatures of the gut microbiota and blood clinical indexes were not restored to the nonplateau status in the Han cohorts, even when the individuals returned to the plain from the plateau for several months. Our study will improve the understanding of the great impact of hypoxic environments on the gut microbiota and blood clinical indexes as well as the adaptation mechanism and intervention targets for plateau adaptation.}, }
@article {pmid31961709, year = {2020}, author = {Lawenius, L and Scheffler, JM and Gustafsson, KL and Henning, P and Nilsson, KH and Colldén, H and Islander, U and Plovier, H and Cani, PD and de Vos, WM and Ohlsson, C and Sjögren, K}, title = {Pasteurized Akkermansia muciniphila protects from fat mass gain but not from bone loss.}, journal = {American journal of physiology. Endocrinology and metabolism}, volume = {318}, number = {4}, pages = {E480-E491}, pmid = {31961709}, issn = {1522-1555}, mesh = {Adipose Tissue/*growth &amp; development/metabolism ; Akkermansia ; Animals ; Calcium Channels/metabolism ; Colon/drug effects/microbiology ; Female ; Femur/drug effects ; Gastrointestinal Microbiome/*physiology ; Lymph Nodes/cytology ; Mice ; Mice, Inbred C57BL ; Osteoporosis/*metabolism ; Ovariectomy ; Parathyroid Hormone/metabolism ; Pasteurization ; Probiotics/*pharmacology ; Serum Amyloid A Protein/metabolism ; Spine/drug effects ; T-Lymphocytes, Regulatory ; TRPV Cation Channels/metabolism ; Verrucomicrobia/*metabolism ; }, abstract = {Probiotic bacteria can protect from ovariectomy (ovx)-induced bone loss in mice. Akkermansia muciniphila is considered to have probiotic potential due to its beneficial effect on obesity and insulin resistance. The purpose of the present study was to determine if treatment with pasteurized Akkermansia muciniphila (pAkk) could prevent ovx-induced bone loss. Mice were treated with vehicle or pAkk for 4 wk, starting 3 days before ovx or sham surgery. Treatment with pAkk reduced fat mass accumulation confirming earlier findings. However, treatment with pAkk decreased trabecular and cortical bone mass in femur and vertebra of gonadal intact mice and did not protect from ovx-induced bone loss. Treatment with pAkk increased serum parathyroid hormone (PTH) levels and increased expression of the calcium transporter Trpv5 in kidney suggesting increased reabsorption of calcium in the kidneys. Serum amyloid A 3 (SAA3) can suppress bone formation and mediate the effects of PTH on bone resorption and bone loss in mice and treatment with pAkk increased serum levels of SAA3 and gene expression of Saa3 in colon. Moreover, regulatory T cells can be protective of bone and pAkk-treated mice had decreased number of regulatory T cells in mesenteric lymph nodes and bone marrow. In conclusion, treatment with pAkk protected from ovx-induced fat mass gain but not from bone loss and reduced bone mass in gonadal intact mice. Our findings with pAkk differ from some probiotics that have been shown to protect bone mass, demonstrating that not all prebiotic and probiotic factors have the same effect on bone.}, }
@article {pmid31961674, year = {2020}, author = {Chang, PT and Rao, K and Longo, LO and Lawton, ES and Scherer, G and Van Arnam, EB}, title = {Thiopeptide Defense by an Ant's Bacterial Symbiont.}, journal = {Journal of natural products}, volume = {83}, number = {3}, pages = {725-729}, doi = {10.1021/acs.jnatprod.9b00897}, pmid = {31961674}, issn = {1520-6025}, mesh = {Animals ; *Antibiosis ; Ants/*microbiology ; Molecular Structure ; Peptides, Cyclic/*chemistry ; Pseudonocardia/*chemistry ; Symbiosis ; Thiazoles/*chemistry ; }, abstract = {Fungus-growing ants and their microbial symbionts have emerged as a model system for understanding antibiotic deployment in an ecological context. Here we establish that bacterial symbionts of the ant Trachymyrmex septentrionalis antagonize their most likely competitors, other strains of ant-associated bacteria, using the thiopeptide antibiotic GE37468. Genomic analysis suggests that these symbionts acquired the GE37468 gene cluster from soil bacteria. This antibiotic, with known activity against human pathogens, was previously identified in a biochemical screen but had no known ecological role. GE37468's host-associated defense role in this insect niche intriguingly parallels the function of similar thiopeptides in the human microbiome.}, }
@article {pmid31954376, year = {2020}, author = {Korpela, K and Salonen, A and Saxen, H and Nikkonen, A and Peltola, V and Jaakkola, T and de Vos, W and Kolho, KL}, title = {Antibiotics in early life associate with specific gut microbiota signatures in a prospective longitudinal infant cohort.}, journal = {Pediatric research}, volume = {88}, number = {3}, pages = {438-443}, pmid = {31954376}, issn = {1530-0447}, mesh = {Amoxicillin/therapeutic use ; Anti-Bacterial Agents/*therapeutic use ; Bifidobacterium/drug effects ; Clostridium/drug effects ; Enterobacteriaceae/drug effects ; Feces ; Female ; *Gastrointestinal Microbiome ; Gene Library ; Hospitalization ; Humans ; Infant ; Infant, Newborn ; Inflammation ; Longitudinal Studies ; Macrolides/therapeutic use ; Male ; Prospective Studies ; Respiratory Syncytial Virus Infections/*microbiology/*virology ; }, abstract = {BACKGROUND: The effects of antibiotics on infant gut microbiota are unclear. We hypothesized that the use of common antibiotics results in long-term aberration in gut microbiota.<br><br>METHODS: Antibiotic-naive infants were prospectively recruited when hospitalized because of a respiratory syncytial virus infection. Composition of fecal microbiota was compared between those receiving antibiotics during follow-up (prescribed at clinicians' discretion because of complications such as otitis media) and those with no antibiotic exposure. Fecal sampling started on day 1, then continued at 2-day intervals during the hospital stay, and at 1, 3 and 6 months at home.<br><br>RESULTS: One hundred and sixty-three fecal samples from 40 patients (median age 2.3 months at baseline; 22 exposed to antibiotics) were available for microbiota analyses. A single course of amoxicillin or macrolide resulted in aberration of infant microbiota characterized by variation in the abundance of bifidobacteria, enterobacteria and clostridia, lasting for several months. Recovery from the antibiotics was associated with an increase in clostridia. Occasionally, antibiotic use resulted in microbiota profiles associated with inflammatory conditions.<br><br>CONCLUSIONS: Antibiotic use in infants modifies especially bifidobacterial levels. Further studies are warranted whether administration of bifidobacteria will provide health benefits by normalizing the microbiota in infants receiving antibiotics.}, }
@article {pmid31949191, year = {2020}, author = {Husso, A and Jalanka, J and Alipour, MJ and Huhti, P and Kareskoski, M and Pessa-Morikawa, T and Iivanainen, A and Niku, M}, title = {The composition of the perinatal intestinal microbiota in horse.}, journal = {Scientific reports}, volume = {10}, number = {1}, pages = {441}, pmid = {31949191}, issn = {2045-2322}, mesh = {Animals ; Animals, Newborn ; Feces/microbiology ; Female ; *Gastrointestinal Microbiome ; Gene Dosage ; Horses ; Mouth/microbiology ; RNA, Ribosomal, 16S/genetics ; Vagina/microbiology ; }, abstract = {The establishment of the intestinal microbiota is critical for the digestive and immune systems. We studied the early development of the rectal microbiota in horse, a hindgut fermenter, from birth until 7 days of age, by qPCR and 16S rRNA gene amplicon sequencing. To evaluate initial sources of the foal microbiota, we characterised dam fecal, vaginal and oral microbiotas. We utilised an amplicon sequence variant (ASV) pipeline to maximise resolution and reproducibility. Stringent ASV filtering based on prevalence and abundance in samples and controls purged contaminants while preserving intestinal taxa. Sampled within 20 minutes after birth, rectal meconium contained small amounts of diverse bacterial DNA, with a profile closer to mare feces than mouth. 24 hours after birth, rectum was colonised by Firmicutes and Proteobacteria, some foals dominated by single genera. At day 7, the rectal genera were still different from adult feces. The mare vaginal microbiota contributed to 24 h and 7 day microbiotas. It contained few lactobacilli, with Corynebacterium, Porphyromonas, Campylobacter and Helcococcus as the most abundant genera. In the oral mucosa, Gemella was extremely abundant. Our observations indicate that bacteria or bacterial components are present in the intestine immediately after birth, but the newborn microbiota changes rapidly.}, }
@article {pmid31944633, year = {2020}, author = {Selway, CA and Eisenhofer, R and Weyrich, LS}, title = {Microbiome applications for pathology: challenges of low microbial biomass samples during diagnostic testing.}, journal = {The journal of pathology. Clinical research}, volume = {6}, number = {2}, pages = {97-106}, pmid = {31944633}, issn = {2056-4538}, mesh = {*Biomass ; DNA, Bacterial/genetics ; *Diagnostic Tests, Routine/methods ; Gastrointestinal Microbiome/*genetics ; Humans ; Microbiota/*genetics ; Sequence Analysis, DNA/methods ; }, abstract = {The human microbiome can play key roles in disease, and diagnostic testing will soon have the ability to examine these roles in the context of clinical applications. Currently, most diagnostic testing in pathology applications focuses on a small number of disease-causing microbes and dismisses the whole microbial community that causes or is modulated by disease. Microbiome modifications have already provided clinically relevant insights in gut and oral diseases, such as irritable bowel disease, but there are currently limitations when clinically examining microbiomes outside of these body sites. This is critical, as the majority of microbial samples used in pathology originate from body sites that contain low concentrations of microbial DNA, including skin, tissue, blood, and urine. These samples, also known as low microbial biomass samples, are difficult to examine without careful consideration and precautions to mitigate contamination and biases. Here, we present the limitations when analysing low microbial biomass samples using current protocols and techniques and highlight the advantages that microbiome testing can offer diagnostics in the future, if the proper precautions are implemented. Specifically, we discuss the sources of contamination and biases that may result in false assessments for these sample types. Finally, we provide recommendations to mitigate contamination and biases from low microbial biomass samples during diagnostic testing, which will be especially important to effectively diagnose and treat patients using microbiome analyses.}, }
@article {pmid31940382, year = {2020}, author = {Jian, C and Luukkonen, P and Yki-Järvinen, H and Salonen, A and Korpela, K}, title = {Quantitative PCR provides a simple and accessible method for quantitative microbiota profiling.}, journal = {PloS one}, volume = {15}, number = {1}, pages = {e0227285}, pmid = {31940382}, issn = {1932-6203}, mesh = {Bacteria/classification/genetics/*isolation &amp; purification ; DNA, Bacterial/genetics/isolation &amp; purification ; Feasibility Studies ; Gene Library ; High-Throughput Nucleotide Sequencing ; High-Throughput Screening Assays/*methods ; Humans ; Microbiota/*genetics ; RNA, Ribosomal, 16S/genetics ; Randomized Controlled Trials as Topic ; *Real-Time Polymerase Chain Reaction ; }, abstract = {The use of relative abundance data from next generation sequencing (NGS) can lead to misinterpretations of microbial community structures, as the increase of one taxon leads to the concurrent decrease of the other(s) in compositional data. Although different DNA- and cell-based methods as well as statistical approaches have been developed to overcome the compositionality problem, and the biological relevance of absolute bacterial abundances has been demonstrated, the human microbiome research has not yet adopted these methods, likely due to feasibility issues. Here, we describe how quantitative PCR (qPCR) done in parallel to NGS library preparation provides an accurate estimation of absolute taxon abundances from NGS data and hence provides an attainable solution to compositionality in high-throughput microbiome analyses. The advantages and potential challenges of the method are also discussed.}, }
@article {pmid31921929, year = {2019}, author = {Zangl, I and Pap, IJ and Aspöck, C and Schüller, C}, title = {The role of Lactobacillus species in the control of Candida via biotrophic interactions.}, journal = {Microbial cell (Graz, Austria)}, volume = {7}, number = {1}, pages = {1-14}, pmid = {31921929}, issn = {2311-2638}, support = {EP-C-16-016/EPA/EPA/United States ; }, abstract = {Microbial communities have an important role in health and disease. Candida spp. are ubiquitous commensals and sometimes opportunistic fungal pathogens of humans, colonizing mucosal surfaces of the genital, urinary, respiratory and gastrointestinal tracts and the oral cavity. They mainly cause local mucosal infections in immune competent individuals. However, in the case of an ineffective immune defense, Candida infections may become a serious threat. Lactobacillus spp. are part of the human microbiome and are natural competitors of Candida in the vaginal environment. Lactic acid, low pH and other secreted metabolites are environmental signals sensed by fungal species present in the microbiome. This review briefly discusses the ternary interaction between host, Lactobacillus species and Candida with regard to fungal infections and the potential antifungal and fungistatic effect of Lactobacillus species. Our understanding of these interactions is incomplete due to the variability of the involved species and isolates and the complexity of the human host.}, }
@article {pmid31921705, year = {2019}, author = {Kang, W and Ji, X and Zhang, X and Tang, D and Feng, Q}, title = {Persistent Exposure to Fusobacterium nucleatum Triggers Chemokine/Cytokine Release and Inhibits the Proliferation and Osteogenic Differentiation Capabilities of Human Gingiva-Derived Mesenchymal Stem Cells.}, journal = {Frontiers in cellular and infection microbiology}, volume = {9}, number = {}, pages = {429}, pmid = {31921705}, issn = {2235-2988}, mesh = {Adult ; Cell Differentiation/genetics/physiology ; Cell Movement/*physiology ; Cell Proliferation/*physiology ; Cells, Cultured ; Chemokines/*metabolism ; Fusobacterium Infections/immunology/pathology ; Fusobacterium nucleatum/*immunology ; Humans ; Mesenchymal Stem Cells/cytology/*metabolism ; Osteogenesis/physiology ; Periodontitis/microbiology/pathology ; Tooth Extraction ; Tooth, Impacted/surgery ; Young Adult ; }, abstract = {Fusobacterium nucleatum is one of the most frequent pathogenic bacteria causing periodontitis. The direct effect of Fusobacterium nucleatum (F. nucleatum) on oral stem cells has rarely been reported. In this study, we aimed to evaluate how gingiva-derived mesenchymal stem cells (GMSCs) respond to a direct challenge with F. nucleatum. GMSCs were isolated by the limiting dilution method and exposed to F. nucleatum at various multiplicities of infection (MOIs; F. nucleatum:cell ratios of 10:1, 50:1, and 100:1) for 24 h to 4 weeks. Our results indicated that F. nucleatum significantly inhibited cell proliferation in a dose-dependent manner and promoted cell migration and the release of chemokines/cytokines, such as CCL2, CXCL1, and IL-6. Additionally, F. nucleatum inhibited GMSC osteogenic differentiation partly by decreasing alkaline phosphatase (ALP) activity, mineralized nodule formation, and osteogenesis-related gene and protein expression. RNA-sequencing analyses indicated that F. nucleatum time-dependently activated cellular signaling pathways during the process of osteogenic differentiation. A total of 64 cell differentiation-related genes were found to be differentially expressed between non-infected and F. nucleatum-infected GMSCs at 3, 7, 14, and 21 d. Intriguingly, we discovered that the 64 cell differentiation-related differentially expressed genes (DEGs) were significantly enriched in cancer-related pathways, such as bone cancer, osteosarcoma and bone marrow cancer, which provides new insight into tumorigenesis during the process of GMSC osteogenic differentiation. In conclusion, this study demonstrates that persistent exposure to F. nucleatum promotes cell migration and chemokine/cytokine release and inhibits the proliferation and osteogenic differentiation of GMSCs. Our study provides a novel and long-time bacteria-cell co-culture in vitro model and makes a foundation for the future mechanistic studies of GMSCs under F. nucleatum infection.}, }
@article {pmid31919630, year = {2020}, author = {Nobile, V and Palumbo, F and Lanni, S and Ghisio, V and Vitali, A and Castagnola, M and Marzano, V and Maulucci, G and De Angelis, C and De Spirito, M and Pacini, L and D'Andrea, L and Ragno, R and Stazi, G and Valente, S and Mai, A and Chiurazzi, P and Genuardi, M and Neri, G and Tabolacci, E}, title = {Altered mitochondrial function in cells carrying a premutation or unmethylated full mutation of the FMR1 gene.}, journal = {Human genetics}, volume = {139}, number = {2}, pages = {227-245}, pmid = {31919630}, issn = {1432-1203}, support = {GGP15257A//Fondazione Telethon/ ; Prot. 201789LFKB//Ministero dell'Istruzione, dell'Universit&#xe0; e della Ricerca/ ; }, mesh = {Ataxia/genetics/metabolism/*pathology ; Case-Control Studies ; Cells, Cultured ; *DNA Methylation ; Fibroblasts/metabolism/pathology ; Fragile X Mental Retardation Protein/genetics/*metabolism ; Fragile X Syndrome/genetics/metabolism/*pathology ; Humans ; Male ; Mitochondria/metabolism/*pathology ; Mitochondrial Proteins/genetics/*metabolism ; *Mutation ; Proteome/*analysis ; RNA, Small Interfering/genetics ; Superoxide Dismutase/antagonists &amp; inhibitors/genetics/metabolism ; Tremor/genetics/metabolism/*pathology ; }, abstract = {Fragile X-related disorders are due to a dynamic mutation of the CGG repeat at the 5' UTR of the FMR1 gene, coding for the RNA-binding protein FMRP. As the CGG sequence expands from premutation (PM, 56-200 CGGs) to full mutation (> 200 CGGs), FMRP synthesis decreases until it is practically abolished in fragile X syndrome (FXS) patients, mainly due to FMR1 methylation. Cells from rare individuals with no intellectual disability and carriers of an unmethylated full mutation (UFM) produce slightly elevated levels of FMR1-mRNA and relatively low levels of FMRP, like in PM carriers. With the aim of clarifying how UFM cells differ from CTRL and FXS cells, a comparative proteomic approach was undertaken, from which emerged an overexpression of SOD2 in UFM cells, also confirmed in PM but not in FXS. The SOD2-mRNA bound to FMRP in UFM more than in the other cell types. The high SOD2 levels in UFM and PM cells correlated with lower levels of superoxide and reactive oxygen species (ROS), and with morphological anomalies and depolarization of the mitochondrial membrane detected through confocal microscopy. The same effect was observed in CTRL and FXS after treatment with MC2791, causing SOD2 overexpression. These mitochondrial phenotypes reverted after knock-down with siRNA against SOD2-mRNA and FMR1-mRNA in UFM and PM. Overall, these data suggest that in PM and UFM carriers, which have high levels of FMR1 transcription and may develop FXTAS, SOD2 overexpression helps to maintain low levels of both superoxide and ROS with signs of mitochondrial degradation.}, }
@article {pmid31918033, year = {2020}, author = {Marzano, V and Tilocca, B and Fiocchi, AG and Vernocchi, P and Levi Mortera, S and Urbani, A and Roncada, P and Putignani, L}, title = {Perusal of food allergens analysis by mass spectrometry-based proteomics.}, journal = {Journal of proteomics}, volume = {215}, number = {}, pages = {103636}, doi = {10.1016/j.jprot.2020.103636}, pmid = {31918033}, issn = {1876-7737}, mesh = {*Allergens/analysis ; Food Analysis ; *Food Hypersensitivity/diagnosis ; Humans ; Mass Spectrometry ; Proteomics ; }, abstract = {Food allergy is the disease where the immune system is elicited by antigens in food. Although innocuous for immune-tolerant individuals, an ever-growing number of food allergenic people are being registered worldwide. To date, no treatment to cure food allergy is available and the disease management relies on the careful exclusion of the allergenic food from the diet of the allergic individuals. Great efforts are ongoing to clarify the allergenic mechanisms of the diverse allergenic proteins of food origin, aimed to both designing suitable therapies and for a timely and precise diagnosis of the allergic condition. Among the other omics sciences, mass spectrometry (MS)-based proteomics is gaining a steadily increasing interest by the whole scientific community acknowledged its high versatility. In the present work, the latest proteomics based-studies on allergenic proteins are reviewed to provide guidance on the different MS-based methodologies adopted in the research on food allergens. Our review points to highlight the strengths of the MS-based proteomics and how these have been exploited to address specific research questions. Also, the most common drawbacks encountered in a proteomic study are discussed, providing an overview that helps novel researchers in choosing the more suitable experimental workflow. SIGNIFICANCE: Wide wealth of knowledge arising from the various MS-based proteomic investigations is improving our understanding of food allergy through molecular characterization of food allergens. The present work reviews the key aspects to be evaluated while investigating food allergens by means of MS-based proteomics and provide guidance to the novel research groups approaching to the fascinating world of MS-based food allergens detection.}, }
@article {pmid31905733, year = {2019}, author = {Signore, F and Gulìa, C and Votino, R and De Leo, V and Zaami, S and Putignani, L and Gigli, S and Santini, E and Bertacca, L and Porrello, A and Piergentili, R}, title = {The Role of Number of Copies, Structure, Behavior and Copy Number Variations (CNV) of the Y Chromosome in Male Infertility.}, journal = {Genes}, volume = {11}, number = {1}, pages = {}, pmid = {31905733}, issn = {2073-4425}, mesh = {Chromosome Aberrations ; Chromosomes, Human, Y/*genetics ; *DNA Copy Number Variations ; Humans ; Infertility, Male/*genetics ; Karyotyping ; Male ; Mutation ; Sequence Analysis, DNA ; }, abstract = {The World Health Organization (WHO) defines infertility as the inability of a sexually active, non-contracepting couple to achieve spontaneous pregnancy within one year. Statistics show that the two sexes are equally at risk. Several causes may be responsible for male infertility; however, in 30-40% of cases a diagnosis of idiopathic male infertility is made in men with normal urogenital anatomy, no history of familial fertility-related diseases and a normal panel of values as for endocrine, genetic and biochemical markers. Idiopathic male infertility may be the result of gene/environment interactions, genetic and epigenetic abnormalities. Numerical and structural anomalies of the Y chromosome represent a minor yet significant proportion and are the topic discussed in this review. We searched the PubMed database and major search engines for reports about Y-linked male infertility. We present cases of Y-linked male infertility in terms of (i) anomalies of the Y chromosome structure/number; (ii) Y chromosome misbehavior in a normal genetic background; (iii) Y chromosome copy number variations (CNVs). We discuss possible explanations of male infertility caused by mutations, lower or higher number of copies of otherwise wild type, Y-linked sequences. Despite Y chromosome structural anomalies are not a major cause of male infertility, in case of negative results and of normal DNA sequencing of the ascertained genes causing infertility and mapping on this chromosome, we recommend an analysis of the karyotype integrity in all cases of idiopathic fertility impairment, with an emphasis on the structure and number of this chromosome.}, }
@article {pmid31904815, year = {2020}, author = {Zhang, X and Yi, N}, title = {Fast zero-inflated negative binomial mixed modeling approach for analyzing longitudinal metagenomics data.}, journal = {Bioinformatics (Oxford, England)}, volume = {36}, number = {8}, pages = {2345-2351}, doi = {10.1093/bioinformatics/btz973}, pmid = {31904815}, issn = {1367-4811}, mesh = {Humans ; Metagenome ; *Metagenomics ; *Microbiota/genetics ; Models, Statistical ; RNA, Ribosomal, 16S/genetics ; }, abstract = {MOTIVATION: Longitudinal metagenomics data, including both 16S rRNA and whole-metagenome shotgun sequencing data, enhanced our abilities to understand the dynamic associations between the human microbiome and various diseases. However, analytic tools have not been fully developed to simultaneously address the main challenges of longitudinal metagenomics data, i.e. high-dimensionality, dependence among samples and zero-inflation of observed counts.<br><br>RESULTS: We propose a fast zero-inflated negative binomial mixed modeling (FZINBMM) approach to analyze high-dimensional longitudinal metagenomic count data. The FZINBMM approach is based on zero-inflated negative binomial mixed models (ZINBMMs) for modeling longitudinal metagenomic count data and a fast EM-IWLS algorithm for fitting ZINBMMs. FZINBMM takes advantage of a commonly used procedure for fitting linear mixed models, which allows us to include various types of fixed and random effects and within-subject correlation structures and quickly analyze many taxa. We found that FZINBMM remarkably outperformed in computational efficiency and was statistically comparable with two R packages, GLMMadaptive and glmmTMB, that use numerical integration to fit ZINBMMs. Extensive simulations and real data applications showed that FZINBMM outperformed other previous methods, including linear mixed models, negative binomial mixed models and zero-inflated Gaussian mixed models.<br><br>FZINBMM has been implemented in the R package NBZIMM, available in the public GitHub repository http://github.com//nyiuab//NBZIMM.<br><br>SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.}, }
@article {pmid31904155, year = {2020}, author = {Cui, JJ and Wang, LY and Tan, ZR and Zhou, HH and Zhan, X and Yin, JY}, title = {MASS SPECTROMETRY-BASED PERSONALIZED DRUG THERAPY.}, journal = {Mass spectrometry reviews}, volume = {39}, number = {5-6}, pages = {523-552}, doi = {10.1002/mas.21620}, pmid = {31904155}, issn = {1098-2787}, mesh = {Anti-Bacterial Agents/pharmacology ; Antineoplastic Agents ; Biomarkers, Pharmacological/analysis ; DNA Methylation/drug effects ; Drug Monitoring/*methods ; Drug Therapy/*methods ; Histones/metabolism ; Humans ; Liquid Biopsy ; Mass Spectrometry/*methods ; Pharmacogenomic Testing/methods ; Precision Medicine/*methods ; }, abstract = {Personalized drug therapy aims to provide tailored treatment for individual patient. Mass spectrometry (MS) is revolutionarily involved in this area because MS is a rapid, customizable, cost-effective, and easy to be used high-throughput method with high sensitivity, specificity, and accuracy. It is driving the formation of a new field, MS-based personalized drug therapy, which currently mainly includes five subfields: therapeutic drug monitoring (TDM), pharmacogenomics (PGx), pharmacomicrobiomics, pharmacoepigenomics, and immunopeptidomics. Gas chromatography-MS (GC-MS) and liquid chromatography-MS (LC-MS) are considered as the gold standard for TDM, which can be used to optimize drug dosage. Matrix-assisted laser desorption ionization-time of flight-MS (MALDI-TOF-MS) significantly improves the capability of detecting biomacromolecule, and largely promotes the application of MS in PGx. It is becoming an indispensable tool for genotyping, which is used to discover and validate genetic biomarkers. In addition, MALDI-TOF-MS also plays important roles in identity of human microbiome whose diversity can explain interindividual differences of drug response. Pharmacoepigenetics is to study the role of epigenetic factors in individualized drug treatment. MS can be used to discover and validate pharmacoepigenetic markers (DNA methylation, histone modification, and noncoding RNA). For the emerging cancer immunotherapy, personalized cancer vaccine has effective immunotherapeutic activity in the clinic. MS-based immunopeptidomics can effectively discover and screen neoantigens. This article systematically reviewed MS-based personalized drug therapy in the above mentioned five subfields. © 2020 John Wiley &amp; Sons Ltd. Mass Spec Rev.}, }
@article {pmid31894374, year = {2020}, author = {Yang, J and Zhang, J and Zhao, C and Gai, Z and Mu, X and Wang, Y and Zhang, C and Su, Z and Gao, L and Zhu, D and Zuo, Z and Heng, X and Zhang, L}, title = {Blood Loss Leads to Increase in Relative Abundance of Opportunistic Pathogens in the Gut Microbiome of Rabbits.}, journal = {Current microbiology}, volume = {77}, number = {3}, pages = {415-424}, pmid = {31894374}, issn = {1432-0991}, support = {81671362//The National Natural Science Foundation of China/ ; 31471202//The National Natural Science Foundation of China/ ; 2018CXGC1219//The Shandong Provincial Key Research and Development Program/ ; 2016YYSP009//The Shandong Provincial Key Research and Development Program/ ; 2016GNS023//Weihai Technique Extension Project/ ; tshw20120206//The Taishan Scholars Program of Shandong Province/ ; }, mesh = {Animals ; Bacteria/genetics/*pathogenicity ; Dysbiosis/*etiology ; Feces/microbiology ; *Gastrointestinal Microbiome ; Hemorrhage/*complications ; Male ; Opportunistic Infections/*etiology/microbiology ; RNA, Ribosomal, 16S/genetics ; Rabbits/microbiology ; }, abstract = {Massive blood loss, a common pathological complication in the clinic, is often accompanied by altered gut integrity and intestinal wall damage. Little is known to what extent the gut microbiome could be correlated with this process. The gut microbiome plays a crucial role in human health, especially in immune and inflammatory responses. This study aims to determine whether acute blood loss affects the gut microbiome and the dynamic variation of the gut microbiome following the loss of blood. We used New Zealand rabbits to mimic the blood loss complication and designed a five-time-point fecal sampling strategy including 24-h pre-blood loss procedure, 24 h, 36 h, 48 h, and 1-week post-blood loss procedure. Gut microbiome composition and diversity were analyzed using 16S rRNA gene sequencing and downstream α-diversity, β-diversity, and taxonomy analysis. The gut microbiome changed dramatically after blood loss procedure. There was a significant increase in diversity and richness of the gut microbiome at 24-h post-procedure (P = 0.038). Based on an analysis of similarities, the composition of gut microbiome in the samples collected at 24-h post-procedure was significantly different from that of pre-procedure samples (r = 0.79, P = 0.004 weighted unifrac distance; r = 0.99, P = 0.002, unweighted unifrac distance). The relative abundance of Lactobacillus was significantly decreased in the post-procedure samples (P = 0.0006), while the relative abundance of Clostridiales (P = 0.018) and Bacteroidales (P = 0.015) was significantly increased after procedure. We also found the relative abundance of Bacilli, Lactobacillus, Myroides, and Prevotella decreased gradually at different time points after blood loss. The relative abundance of the Clostridia, Alphaproteobacteria, and Sporosarcina increased at 24-h post-procedure and decreased thereafter. This preliminary study discovered potential connections between blood loss and dysbiosis of gut microbiome. The diversity and abundance of the gut microbiome was affected to various extents after acute blood loss and unable to be restored to the original microbiome profile even after one week. The increase in relative abundance of opportunistic pathogens after blood loss could be an important indication to reconsider immune and inflammatory responses after acute blood loss from the perspective of gut microbiome.}, }
@article {pmid33814114, year = {2020}, author = {Hopson, LM and Singleton, SS and David, JA and Basuchoudhary, A and Prast-Nielsen, S and Klein, P and Sen, S and Mazumder, R}, title = {Bioinformatics and machine learning in gastrointestinal microbiome research and clinical application.}, journal = {Progress in molecular biology and translational science}, volume = {176}, number = {}, pages = {141-178}, doi = {10.1016/bs.pmbts.2020.08.011}, pmid = {33814114}, issn = {1878-0814}, mesh = {Computational Biology ; *Gastrointestinal Microbiome ; Humans ; Machine Learning ; Metagenomics ; }, abstract = {The scientific community currently defines the human microbiome as all the bacteria, viruses, fungi, archaea, and eukaryotes that occupy the human body. When considering the variable locations, composition, diversity, and abundance of our microbial symbionts, the sheer volume of microorganisms reaches hundreds of trillions. With the onset of next generation sequencing (NGS), also known as high-throughput sequencing (HTS) technologies, the barriers to studying the human microbiome lowered significantly, making in-depth microbiome research accessible. Certain locations on the human body, such as the gastrointestinal, oral, nasal, and skin microbiomes have been heavily studied through community-focused projects like the Human Microbiome Project (HMP). In particular, the gastrointestinal microbiome (GM) has received significant attention due to links to neurological, immunological, and metabolic diseases, as well as cancer. Though HTS technologies allow deeper exploration of the GM, data informing the functional characteristics of microbiota and resulting effects on human function or disease are still sparse. This void is compounded by microbiome variability observed among humans through factors like genetics, environment, diet, metabolic activity, and even exercise; making GM research inherently difficult to study. This chapter describes an interdisciplinary approach to GM research with the goal of mitigating the hindrances of translating findings into a clinical setting. By applying tools and knowledge from microbiology, metagenomics, bioinformatics, machine learning, predictive modeling, and clinical study data from children with treatment-resistant epilepsy, we describe a proof-of-concept approach to clinical translation and precision application of GM research.}, }
@article {pmid33814111, year = {2020}, author = {Kennedy, MS and Chang, EB}, title = {The microbiome: Composition and locations.}, journal = {Progress in molecular biology and translational science}, volume = {176}, number = {}, pages = {1-42}, pmid = {33814111}, issn = {1878-0814}, support = {T32 GM007281/GM/NIGMS NIH HHS/United States ; }, mesh = {Gastrointestinal Tract ; Humans ; *Microbiota ; }, abstract = {The human body is home to a diverse and functionally important assemblage of symbiotic microbes that varies predictably over different spatial scales, both within and across body sites. The composition of these spatially distinct microbial consortia can be impacted by a variety of stochastic and deterministic forces, including dispersal from different source communities, and selection by regionally-specific host processes for the enrichment of physiologically significant taxa. In this chapter, we review the composition, function, and assembly of the healthy human gastrointestinal, skin, vaginal, and respiratory microbiomes, with special emphasis on the regional distribution of microbes throughout the gastrointestinal tract.}, }
@article {pmid31889089, year = {2019}, author = {Gavin, DP and Reen, FJ and Rocha-Martin, J and Abreu-Castilla, I and Woods, DF and Foley, AM and Sánchez-Murcia, PA and Schwarz, M and O'Neill, P and Maguire, AR and O'Gara, F}, title = {Genome mining and characterisation of a novel transaminase with remote stereoselectivity.}, journal = {Scientific reports}, volume = {9}, number = {1}, pages = {20285}, pmid = {31889089}, issn = {2045-2322}, mesh = {Amino Acid Sequence ; *Computational Biology/methods ; *Data Mining ; Enzyme Activation ; *Genome ; *Genomics/methods ; Models, Molecular ; Molecular Structure ; Phylogeny ; Stereoisomerism ; Structure-Activity Relationship ; Transaminases/*chemistry/*genetics/metabolism ; }, abstract = {Microbial enzymes from pristine niches can potentially deliver disruptive opportunities in synthetic routes to Active Pharmaceutical Ingredients and intermediates in the Pharmaceutical Industry. Advances in green chemistry technologies and the importance of stereochemical control, further underscores the application of enzyme-based solutions in chemical synthesis. The rich tapestry of microbial diversity in the oceanic ecosystem encodes a capacity for novel biotransformations arising from the chemical complexity of this largely unexplored bioactive reservoir. Here we report a novel ω-transaminase discovered in a marine sponge Pseudovibrio sp. isolate. Remote stereoselection using a transaminase has been demonstrated for the first time using this novel protein. Application to the resolution of an intermediate in the synthesis of sertraline highlights the synthetic potential of this novel biocatalyst discovered through genomic mining. Integrated chemico-genomics revealed a unique substrate profile, while molecular modelling provided structural insights into this 'first in class' selectivity at a remote chiral centre.}, }
@article {pmid31887978, year = {2019}, author = {Picca, A and Ponziani, FR and Calvani, R and Marini, F and Biancolillo, A and Coelho-Junior, HJ and Gervasoni, J and Primiano, A and Putignani, L and Del Chierico, F and Reddel, S and Gasbarrini, A and Landi, F and Bernabei, R and Marzetti, E}, title = {Gut Microbial, Inflammatory and Metabolic Signatures in Older People with Physical Frailty and Sarcopenia: Results from the BIOSPHERE Study.}, journal = {Nutrients}, volume = {12}, number = {1}, pages = {}, pmid = {31887978}, issn = {2072-6643}, support = {IMI-JU #115621//Innovative Medicines Initiative/ ; D3.2 2013//Intramural Research Grants from the Universit&#xe0; Cattolica del Sacro Cuore/ ; D3.2 2015//Intramural Research Grants from the Universit&#xe0; Cattolica del Sacro Cuore/ ; NA//Nonprofit research foundation "Centro Studi Achille e Linda Lorenzon"/ ; CAPES; Finance Code 001//Coordena&#xe7;&#xe3;o de Aperfei&#xe7;oamento de Pessoal de N&#xed;vel Superior/ ; }, mesh = {Aged ; Amino Acids/metabolism ; Cohort Studies ; Cytokines/blood ; Female ; Frail Elderly ; *Frailty/complications/epidemiology/metabolism ; Gastrointestinal Microbiome/*physiology ; Humans ; Inflammation/*metabolism ; Male ; *Sarcopenia/complications/epidemiology/metabolism ; }, abstract = {Physical frailty and sarcopenia (PF&amp;S) share multisystem derangements, including variations in circulating amino acids and chronic low-grade inflammation. Gut microbiota balances inflammatory responses in several conditions and according to nutritional status. Therefore, an altered gut-muscle crosstalk has been hypothesized in PF&amp;S. We analyzed the gut microbial taxa, systemic inflammation, and metabolic characteristics of older adults with and without PF&amp;S. An innovative multi-marker analytical approach was applied to explore the classification performance of potential biomarkers for PF&amp;S. Thirty-five community dwellers aged 70+, 18 with PF&amp;S, and 17 nonPF&amp;S controls were enrolled. Sequential and Orthogonalized Covariance Selection (SO-CovSel), a multi-platform regression method developed to handle highly correlated variables, was applied. The SO-CovSel model with the best prediction ability using the smallest number of variables was built using seven mediators. The model correctly classified 91.7% participants with PF&amp;S and 87.5% nonPF&amp;S controls. Compared with the latter group, PF&amp;S participants showed higher serum concentrations of aspartic acid, lower circulating levels of concentrations of threonine and macrophage inflammatory protein 1α, increased abundance of Oscillospira and Ruminococcus microbial taxa, and decreased abundance of Barnesiellaceae and Christensenellaceae. Future investigations are warranted to determine whether these biomediators are involved in PF&amp;S pathophysiology and may, therefore, provide new targets for interventions.}, }
@article {pmid31886477, year = {2021}, author = {Tomassi, D and Forzani, L and Duarte, S and Pfeiffer, RM}, title = {Sufficient dimension reduction for compositional data.}, journal = {Biostatistics (Oxford, England)}, volume = {22}, number = {4}, pages = {687-705}, pmid = {31886477}, issn = {1468-4357}, mesh = {Humans ; Likelihood Functions ; *Microbiota ; }, abstract = {Recent efforts to characterize the human microbiome and its relation to chronic diseases have led to a surge in statistical development for compositional data. We develop likelihood-based sufficient dimension reduction methods (SDR) to find linear combinations that contain all the information in the compositional data on an outcome variable, i.e., are sufficient for modeling and prediction of the outcome. We consider several models for the inverse regression of the compositional vector or transformations of it, as a function of outcome. They include normal, multinomial, and Poisson graphical models that allow for complex dependencies among observed counts. These methods yield efficient estimators of the reduction and can be applied to continuous or categorical outcomes. We incorporate variable selection into the estimation via penalties and address important invariance issues arising from the compositional nature of the data. We illustrate and compare our methods and some established methods for analyzing microbiome data in simulations and using data from the Human Microbiome Project. Displaying the data in the coordinate system of the SDR linear combinations allows visual inspection and facilitates comparisons across studies.}, }
@article {pmid31883524, year = {2019}, author = {Manara, S and Asnicar, F and Beghini, F and Bazzani, D and Cumbo, F and Zolfo, M and Nigro, E and Karcher, N and Manghi, P and Metzger, MI and Pasolli, E and Segata, N}, title = {Microbial genomes from non-human primate gut metagenomes expand the primate-associated bacterial tree of life with over 1000 novel species.}, journal = {Genome biology}, volume = {20}, number = {1}, pages = {299}, pmid = {31883524}, issn = {1474-760X}, mesh = {Animals ; *Gastrointestinal Microbiome ; Humans ; *Metagenome ; Phylogeny ; Primates/*microbiology ; Treponema/genetics ; }, abstract = {BACKGROUND: Humans have coevolved with microbial communities to establish a mutually advantageous relationship that is still poorly characterized and can provide a better understanding of the human microbiome. Comparative metagenomic analysis of human and non-human primate (NHP) microbiomes offers a promising approach to study this symbiosis. Very few microbial species have been characterized in NHP microbiomes due to their poor representation in the available cataloged microbial diversity, thus limiting the potential of such comparative approaches.<br><br>RESULTS: We reconstruct over 1000 previously uncharacterized microbial species from 6 available NHP metagenomic cohorts, resulting in an increase of the mappable fraction of metagenomic reads by 600%. These novel species highlight that almost 90% of the microbial diversity associated with NHPs has been overlooked. Comparative analysis of this new catalog of taxa with the collection of over 150,000 genomes from human metagenomes points at a limited species-level overlap, with only 20% of microbial candidate species in NHPs also found in the human microbiome. This overlap occurs mainly between NHPs and non-Westernized human populations and NHPs living in captivity, suggesting that host lifestyle plays a role comparable to host speciation in shaping the primate intestinal microbiome. Several NHP-specific species are phylogenetically related to human-associated microbes, such as Elusimicrobia and Treponema, and could be the consequence of host-dependent evolutionary trajectories.<br><br>CONCLUSIONS: The newly reconstructed species greatly expand the microbial diversity associated with NHPs, thus enabling better interrogation of the primate microbiome and empowering in-depth human and non-human comparative and co-diversification studies.}, }
@article {pmid31876898, year = {2020}, author = {Harkins, CP and Kong, HH and Segre, JA}, title = {Manipulating the Human Microbiome to Manage Disease.}, journal = {JAMA}, volume = {323}, number = {4}, pages = {303-304}, doi = {10.1001/jama.2019.19602}, pmid = {31876898}, issn = {1538-3598}, mesh = {Child ; Child Nutrition Disorders/diet therapy/microbiology ; Clostridium Infections/therapy ; *Disease Management ; Fecal Microbiota Transplantation ; Female ; Gastrointestinal Microbiome ; HIV Infections/drug therapy ; Humans ; Infant, Newborn ; *Microbiota ; Neonatal Sepsis/prevention &amp; control ; Vagina/microbiology ; }, }
@article {pmid31875448, year = {2019}, author = {Zhou, ZY and Xu, X and Zhou, Y}, title = {[Research progress on carbohydrate active enzymes of human microbiome].}, journal = {Hua xi kou qiang yi xue za zhi = Huaxi kouqiang yixue zazhi = West China journal of stomatology}, volume = {37}, number = {6}, pages = {666-670}, pmid = {31875448}, issn = {2618-0456}, mesh = {Carbohydrates ; *Gastrointestinal Tract ; Humans ; *Microbiota ; }, abstract = {A massive variety of microorganisms live in and on the human body, especially at oral, skin, vaginal, gastroin-testinal, and respiratory sites. The complicated metabolic activities of microorganisms assist human digestive function and participate in a series of physiological and pathogenetic processes. Carbohydrate-active enzymes (CAZymes) are a series of enzymes that function in degradation, modification, and formation of glycoside bonds. Microbes regulate the physiological and pathogenetic processes of human body by producing various CAZymes to degrade and modify complex carbohydrates and generate signal molecules for further utilization in human cells. Here, we reviewed the mechanisms of complex carbohy-drate metabolism and related microbial CAZymes, especially in digestive tract and oral cavity. We also summarized the rela-tionship between microbial CAZymes and human health, and proposed potential applications.}, }
@article {pmid31874963, year = {2019}, author = {Majid, M and Andleeb, S}, title = {Designing a multi-epitopic vaccine against the enterotoxigenic Bacteroides fragilis based on immunoinformatics approach.}, journal = {Scientific reports}, volume = {9}, number = {1}, pages = {19780}, pmid = {31874963}, issn = {2045-2322}, mesh = {*Bacterial Proteins/chemistry/genetics/immunology ; *Bacterial Vaccines/chemistry/genetics/immunology ; *Bacteroides fragilis/chemistry/genetics/immunology ; *Computational Biology ; *Epitopes/chemistry/genetics/immunology ; Humans ; *Molecular Docking Simulation ; Toll-Like Receptor 2/chemistry/genetics/immunology ; }, abstract = {Enterotoxigenic Bacteroides fragilis is an enteric pathogen which is described as a causative agent of various intestinal infections and inflammatory diseases. Moreover, various research studies have reported it to be a leading factor in the development of colorectal cancer. As a part of the normal human microbiome, its treatment has become quite a challenge due to the alarming resistance against the available antibiotics. Although, this particular strain of B. fragilis shows susceptibility to few antibiotics, it is pertinent to devise an effective vaccine strategy for its elimination. There is no vaccine available against this pathogen up to date; therefore, we systematically ventured the outer membrane toxin producing proteins found exclusively in the toxigenic B. fragilis through the in-silico approaches to predict a multi-epitopic chimeric vaccine construct. The designed protein constitutes of epitopes which are predicted for linear B cells, Helper and T cells of outer membrane proteins expected to be putative vaccine candidates. The finalized proteins are only expressed in the enterotoxigenic B. fragilis, thus proving them to be exclusive. The 3D structure of the protein was first predicted followed by its refinement and validation via utilizing the bioinformatic approaches. Docking of the designed protein with the TLR2 receptor forecasted apt binding. Upon immune simulation, notable levels were observed in the expression of the immune cells.}, }
@article {pmid31872558, year = {2019}, author = {Grosicki, GJ and Durk, RP and Bagley, JR}, title = {Rapid gut microbiome changes in a world-class ultramarathon runner.}, journal = {Physiological reports}, volume = {7}, number = {24}, pages = {e14313}, pmid = {31872558}, issn = {2051-817X}, mesh = {Adult ; Athletes ; *Gastrointestinal Microbiome ; Humans ; Lactic Acid/blood ; Male ; Oxygen Consumption ; Physical Exertion ; *Running ; }, abstract = {The human gut microbiome is a dynamic ecosystem with prolific health connotations. Physical activity is emerging as a potent regulator of human microbiome composition. This study examined changes in the gut microbiome of a world-class ultramarathon runner before and after competing in the Western States Endurance Run (WSER), a 163 km mountain footrace. Anthropometrics and body composition were assessed and the ultramarathoner's submaximal and maximal performance profiles were evaluated. Gut microbiome analyses were performed at four time-points: 21 weeks and 2 weeks before and 2 hours and 10 days after WSER. Aerobic power (VO2 max) was 4.24 L/min (66.7 ml kg[-1] min[-1]), and running economy (51.1 ml kg[-1] min[-1] at 268 m/min) and lactate threshold (~83% VO2 max) values were comparable to that of highly trained distance runners. Two hours post-race, considerable changes in the ultrarunners' gut microbiome were observed. Alpha diversity (Shannon Diversity Index) increased from 2.73 to 2.80 and phylum-level bacterial composition (Firmicutes/Bacteroidetes ratio) rose from 4.4 to 14.2. Underlying these macro-level microbial alterations were demonstrable increases in select bacterial genera such as Veillonella (+14,229%) and Streptococcus (+438%) concomitant with reductions in Alloprevotella (-79%) and Subdolingranulum (-50%). To our knowledge, this case study shows the most rapid and pronounced shifts in human gut microbiome composition after acute exercise in the human literature. These findings provide yet another example of how exercise can be a powerful modulator of human health.}, }
@article {pmid31870912, year = {2020}, author = {Ly, LK and Rowles, JL and Paul, HM and Alves, JMP and Yemm, C and Wolf, PM and Devendran, S and Hudson, ME and Morris, DJ and Erdman, JW and Ridlon, JM}, title = {Bacterial steroid-17,20-desmolase is a taxonomically rare enzymatic pathway that converts prednisone to 1,4-androstanediene-3,11,17-trione, a metabolite that causes proliferation of prostate cancer cells.}, journal = {The Journal of steroid biochemistry and molecular biology}, volume = {199}, number = {}, pages = {105567}, pmid = {31870912}, issn = {1879-1220}, support = {T32 CA057699/CA/NCI NIH HHS/United States ; }, mesh = {Adrenal Glands/metabolism ; Androgens/metabolism ; Androstadienes/*metabolism ; Cell Line, Tumor ; Cell Proliferation/genetics ; Clostridiales/enzymology ; Glucocorticoids/*metabolism ; Humans ; Hydrocortisone/metabolism ; Male ; Metabolic Networks and Pathways/genetics ; Phylogeny ; Prednisolone/metabolism ; Prednisone/metabolism ; Propionibacteriaceae/enzymology ; Prostatic Neoplasms/enzymology/genetics/*metabolism/pathology ; Steroid 17-alpha-Hydroxylase/genetics/*metabolism ; }, abstract = {The adrenal gland has traditionally been viewed as a source of "weak androgens"; however, emerging evidence indicates 11-oxy-androgens of adrenal origin are metabolized in peripheral tissues to potent androgens. Also emerging is the role of gut bacteria in the conversion of C21 glucocorticoids to 11-oxygenated C19 androgens. Clostridium scindens ATCC 35,704 is a gut microbe capable of converting cortisol into 11-oxy-androgens by cleaving the side-chain. The desA and desB genes encode steroid-17,20-desmolase. Our prior study indicated that the urinary tract bacterium, Propionimicrobium lymphophilum ACS-093-V-SCH5 encodes desAB and converts cortisol to 11β-hydroxyandrostenedione. We wanted to determine how widespread this function occurs in the human microbiome. Phylogenetic and sequence similarity network analyses indicated that the steroid-17,20-desmolase pathway is taxonomically rare and located in gut and urogenital microbiomes. Two microbes from each of these niches, C. scindens and Propionimicrobium lymphophilum, respectively, were screened for activity against endogenous (cortisol, cortisone, and allotetrahydrocortisol) and exogenous (prednisone, prednisolone, dexamethasone, and 9-fluorocortisol) glucocorticoids. LC/MS analysis showed that both microbes were able to side-chain cleave all glucocorticoids, forming 11-oxy-androgens. Pure recombinant DesAB from C. scindens showed the highest activity against prednisone, a commonly prescribed glucocorticoid. In addition, 0.1 nM 1,4-androstadiene-3,11,17-trione, bacterial side-chain cleavage product of prednisone, showed significant proliferation relative to vehicle in androgen-dependent growth LNCaP prostate cancer cells after 24 h (2.3 fold; P < 0.01) and 72 h (1.6 fold; P < 0.01). Taken together, DesAB-expressing microbes may be an overlooked source of androgens in the body, potentially contributing to various disease states, such as prostate cancer.}, }
@article {pmid31866425, year = {2020}, author = {Liu, Q and Liu, Q and Meng, H and Lv, H and Liu, Y and Liu, J and Wang, H and He, L and Qin, J and Wang, Y and Dai, Y and Otto, M and Li, M}, title = {Staphylococcus epidermidis Contributes to Healthy Maturation of the Nasal Microbiome by Stimulating Antimicrobial Peptide Production.}, journal = {Cell host &amp; microbe}, volume = {27}, number = {1}, pages = {68-78.e5}, pmid = {31866425}, issn = {1934-6069}, support = {ZIA AI000904/ImNIH/Intramural NIH HHS/United States ; ZIA AI000904/AI/NIAID NIH HHS/United States ; }, mesh = {Adult ; Aged, 80 and over ; Antimicrobial Cationic Peptides/*biosynthesis ; Biofilms/growth &amp; development ; Cell Line ; Child ; Child, Preschool ; Epidermal Cells ; Female ; High-Throughput Nucleotide Sequencing ; Host Microbial Interactions ; Humans ; Immunity, Innate ; Male ; Metagenomics ; Microbiota/*immunology ; Nasal Cavity/*microbiology ; RNA, Ribosomal, 16S ; *Staphylococcus epidermidis/isolation &amp; purification/metabolism ; Symbiosis ; Young Adult ; }, abstract = {The composition of the human microbiome profoundly impacts human well-being. However, the mechanisms underlying microbiome maturation are poorly understood. The nasal microbiome is of particular importance as a source of many respiratory infections. Here, we performed a large sequencing and culture-based analysis of the human nasal microbiota from different age groups. We observed a significant decline of pathogenic bacteria before adulthood, with an increase of the commensal Staphylococcus epidermidis. In seniors, this effect was partially reversed. In vitro, many S. epidermidis isolates stimulated nasal epithelia to produce antimicrobial peptides, killing pathogenic competitors, while S. epidermidis itself proved highly resistant owing to its exceptional capacity to form biofilms. Furthermore, S. epidermidis isolates with high antimicrobial peptide-inducing and biofilm-forming capacities outcompeted pathogenic bacteria during nasal colonization in vivo. Our study identifies a pivotal role of S. epidermidis in healthy maturation of the nasal microbiome, which is achieved at least in part by symbiotic cooperation with innate host defense.}, }
@article {pmid31861722, year = {2019}, author = {Deering, KE and Devine, A and O'Sullivan, TA and Lo, J and Boyce, MC and Christophersen, CT}, title = {Characterizing the Composition of the Pediatric Gut Microbiome: A Systematic Review.}, journal = {Nutrients}, volume = {12}, number = {1}, pages = {}, pmid = {31861722}, issn = {2072-6643}, support = {NA//Edith Cowan University/ ; }, mesh = {Bacteria/classification/*genetics ; Child ; Diet ; *Gastrointestinal Microbiome ; Humans ; RNA, Bacterial/genetics ; RNA, Ribosomal, 16S/genetics ; }, abstract = {The consortium of trillions of microorganisms that live inside the human gut are integral to health. Little has been done to collate and characterize the microbiome of children. A systematic review was undertaken to address this gap (PROSPERO ID: CRD42018109599). MEDLINE and EMBASE were searched using the keywords: "healthy preadolescent children" and "gut microbiome" to 31 August 2018. Of the 815 journal articles, 42 met the inclusion criteria. The primary outcome was the relative abundance of bacteria at the phylum, family, and genus taxonomic ranks. α-diversity, short chain fatty acid concentrations, diet, 16S rRNA sequencing region, and geographical location were documented. The preadolescent gut microbiome is dominated at the phylum level by Firmicutes (weighted overall average relative abundance = 51.1%) and Bacteroidetes (36.0%); genus level by Bacteroides (16.0%), Prevotella (8.69%), Faecalibacterium (7.51%), and Bifidobacterium (5.47%). Geographic location and 16S rRNA sequencing region were independently associated with microbial proportions. There was limited consensus between studies that reported α-diversity and short chain fatty acids. Broadly speaking, participants from non-Western locations, who were less likely to follow a Westernized dietary pattern, had higher α-diversity and SCFA concentrations. Confirmatory studies will increase the understanding of the composition and functional capacity of the preadolescent gut microbiome.}, }
@article {pmid31857734, year = {2020}, author = {Martiny, JBH and Whiteson, KL and Bohannan, BJM and David, LA and Hynson, NA and McFall-Ngai, M and Rawls, JF and Schmidt, TM and Abdo, Z and Blaser, MJ and Bordenstein, S and Bréchot, C and Bull, CT and Dorrestein, P and Eisen, JA and Garcia-Pichel, F and Gilbert, J and Hofmockel, KS and Holtz, ML and Knight, R and Mark Welch, DB and McDonald, D and Methé, B and Mouncey, NJ and Mueller, NT and Pfister, CA and Proctor, L and Sachs, JL}, title = {The emergence of microbiome centres.}, journal = {Nature microbiology}, volume = {5}, number = {1}, pages = {2-3}, pmid = {31857734}, issn = {2058-5276}, support = {K01 HL141589/HL/NHLBI NIH HHS/United States ; R21 AI149354/AI/NIAID NIH HHS/United States ; N00014-19-1-2313//United States Department of Defense | United States Navy | Office of Naval Research (ONR)/International ; DEB-1925761//NSF | BIO | Division of Environmental Biology (DEB)/International ; }, mesh = {Animals ; Capital Financing ; Communication ; Humans ; Interdisciplinary Research/economics/*organization &amp; administration/*trends ; *Microbiota ; }, }
@article {pmid31850811, year = {2019}, author = {Lo Presti, A and Del Chierico, F and Altomare, A and Zorzi, F and Cella, E and Putignani, L and Guarino, MPL and Monteleone, G and Cicala, M and Angeletti, S and Ciccozzi, M}, title = {Exploring the genetic diversity of the 16S rRNA gene of Akkermansia muciniphila in IBD and IBS.}, journal = {Future microbiology}, volume = {14}, number = {}, pages = {1497-1509}, doi = {10.2217/fmb-2019-0175}, pmid = {31850811}, issn = {1746-0921}, mesh = {Adult ; Akkermansia ; Evolution, Molecular ; Feces/microbiology ; Gastrointestinal Microbiome ; *Genetic Variation ; Humans ; Inflammatory Bowel Diseases/*microbiology ; Irritable Bowel Syndrome/*microbiology ; Middle Aged ; Phylogeny ; Polymorphism, Single Nucleotide ; RNA, Bacterial/genetics ; RNA, Ribosomal, 16S/*genetics ; Verrucomicrobia/*genetics ; }, abstract = {Aim: The human gastrointestinal tract harbors diverse, abundant microbiota and Akkermansia muciniphila is involved in this community. The aim of this study is to characterize 16 new A. muciniphila 16S ribosomal RNA sequences selected from a metagenomic database from stools of patients with irritable bowel syndrome (IBS), inflammatory bowel diseases and control (CTRLs) subjects by a phylogenetic approach. Materials &amp; methods: A phylogenetic approach was used to study the genetic diversity and SNPs in 16 A. muciniphila 16S ribosomal RNA sequences from stools of 107 individuals, 36 of which were patients affected by IBS, 30 by inflammatory bowel disease and 41 were CTRLs. Results: Phylogenetic analysis confirmed the subdivision into different supported clusters. An increase of variability in IBS has been identified. Conclusion: The genetic variation combined to the relative abundance, contribute to the protective role of A. muciniphila. Phylogenesis represent an additional approach to investigate genetic variability.}, }
@article {pmid31850333, year = {2019}, author = {Song, N and Liu, X and Feng, Q and Xu, M and Lan, X and Li, M and Liu, R and Li, C and Dong, T and Wang, D and Liu, S}, title = {Whole Body Vibration Triggers a Change in the Mutual Shaping State of Intestinal Microbiota and Body's Immunity.}, journal = {Frontiers in bioengineering and biotechnology}, volume = {7}, number = {}, pages = {377}, pmid = {31850333}, issn = {2296-4185}, abstract = {Whole body vibration (WBV) is a non-invasive physical therapy that has recently been included in the hospital's patient rehabilitation training catalog, but its health effects have not been sufficiently studied. In the present study, to examine the possible effects of WBV on immune cell differentiation, the IFN, IL-4,-17, F4/80 and CD3,-4,-8,-11b,-11c,-19 markers were used to characterizing the cells in mouse spleen. The results showed that the CD4 and CD25 positive lymphocytes in the spleen were significantly increased in the WBV group, and the population of Treg cells was enhanced significantly in response to WBV. Since the differentiation in immune cells is usually associated with microbiota, therefore the intestinal flora was characterized in mice and human individuals. The results indicated that WBV significantly reduced the α-diversity of mouse intestinal microbiota. Moreover, the principal coordinate analysis (PCoA) results indicated that the β-diversities of both mice and human fecal microbiota increased after WBV. Analysis of the bacterial composition indicated that the contents of a variety of bacteria changed in mice upon the stimulation of vibration, such as Lactobacillus animalis in mice, and Lactobacillus paraplantarum and Lactobacillus sanfranciscensis in human. The succeeding correlation analysis revealed that some bacteria with significant content variations were correlated to the regulatory T cell differentiation in mice and physical characteristics in human. Our research will provide the basis for future non-invasive treatment of microbial and immune related diseases.}, }
@article {pmid31849833, year = {2019}, author = {Sutton, TDS and Hill, C}, title = {Gut Bacteriophage: Current Understanding and Challenges.}, journal = {Frontiers in endocrinology}, volume = {10}, number = {}, pages = {784}, pmid = {31849833}, issn = {1664-2392}, abstract = {The gut microbiome is widely accepted to have a significant impact on human health yet, despite years of research on this complex ecosystem, the contributions of different forces driving microbial population structure remain to be fully elucidated. The viral component of the human gut microbiome is dominated by bacteriophage, which are known to play crucial roles in shaping microbial composition, driving bacterial diversity, and facilitating horizontal gene transfer. Bacteriophage are also one of the most poorly understood components of the human gut microbiome, with the vast majority of viral sequences sharing little to no homology to reference databases. If we are to understand the dynamics of bacteriophage populations, their interaction with the human microbiome and ultimately their influence on human health, we will depend heavily on sequence based approaches and in silico tools. This is complicated by the fact that, as with any research field in its infancy, methods of analyses vary and this can impede our ability to compare the outputs of different studies. Here, we discuss the major findings to date regarding the human virome and reflect on our current understanding of how gut bacteriophage shape the microbiome. We consider whether or not the virome field is built on unstable foundations and if so, how can we provide a solid basis for future experimentation. The virome is a challenging yet crucial piece of the human microbiome puzzle. In order to develop our understanding, we will discuss the need to underpin future studies with robust research methods and suggest some solutions to existing challenges.}, }
@article {pmid31848308, year = {2019}, author = {Wang, C and Li, P and Yan, Q and Chen, L and Li, T and Zhang, W and Li, H and Chen, C and Han, X and Zhang, S and Xu, M and Li, B and Zhang, X and Ni, H and Ma, Y and Dong, B and Li, S and Liu, S}, title = {Characterization of the Pig Gut Microbiome and Antibiotic Resistome in Industrialized Feedlots in China.}, journal = {mSystems}, volume = {4}, number = {6}, pages = {}, pmid = {31848308}, issn = {2379-5077}, abstract = {To characterize the diversity and richness and explore the function and structure of swine gut microbiome and resistome in common pig-farming feedlots, we sampled and metagenomic sequenced the feces of pigs from four different industrialized feedlots located in four distant provinces across China. Surprisingly, more than half of the nonredundant genes (1,937,648, 54.3%) in the current catalogue were newly found compared with the previously published reference gene catalogue (RGC) of the pig gut microbiome. Additionally, 16 high-completeness draft genomes were obtained by analyzing the dominant species on each feedlot. Notably, seven of these species often appeared in the human body sites. Despite a smaller number of nonredundant genes, our study identified more antibiotic resistance genes than those available in the RGC. Tetracycline, aminoglycoside, and multidrug resistance genes accounted for nearly 70% of the relative abundance in the current catalogue. Slightly higher sharing ratios were shown between the industrialized feedlot pig gut microbiomes and human gut microbiomes than that between the RGC and human counterpart (14.7% versus 12.6% in genes and 94.1% versus 87.7% in functional groups, respectively). Furthermore, a remarkably high number of the antibiotic resistance proteins (n =141) were identified to be shared by the pig, human, and mouse resistome, indicating the potential for horizontal transfer of resistance genes. Of the antibiotic resistance proteins shared by pigs and humans, 50 proteins were related to tetracycline resistance, and 49 were related to aminoglycoside resistance.IMPORTANCE The gut microbiota is believed to be closely related to many important physical functions in the host. Comprehensive data on mammalian gut metagenomes has facilitated research on host-microbiome interaction mechanisms, but less is known about pig gut microbiome, especially the gut microbiome in industrialized feedlot pigs, compared with human microbiome. On the other hand, pig production, as an important source of food, is believed to exacerbate the antibiotic resistance in humans due to the abuse of antibiotics in pig production in various parts of the world. This study delineates an intricate picture of swine gut microbiome and antibiotic resistome in industrialized feedlots and may provide insight for the pig producing industry.}, }
@article {pmid31848304, year = {2019}, author = {Wang, Y and Randolph, TW and Shojaie, A and Ma, J}, title = {The Generalized Matrix Decomposition Biplot and Its Application to Microbiome Data.}, journal = {mSystems}, volume = {4}, number = {6}, pages = {}, pmid = {31848304}, issn = {2379-5077}, support = {R01 GM129512/GM/NIGMS NIH HHS/United States ; K01 HL124050/HL/NHLBI NIH HHS/United States ; R01 CA192222/CA/NCI NIH HHS/United States ; S10 OD020069/OD/NIH HHS/United States ; R01 GM114029/GM/NIGMS NIH HHS/United States ; P01 CA168530/CA/NCI NIH HHS/United States ; }, abstract = {Exploratory analysis of human microbiome data is often based on dimension-reduced graphical displays derived from similarities based on non-Euclidean distances, such as UniFrac or Bray-Curtis. However, a display of this type, often referred to as the principal-coordinate analysis (PCoA) plot, does not reveal which taxa are related to the observed clustering because the configuration of samples is not based on a coordinate system in which both the samples and variables can be represented. The reason is that the PCoA plot is based on the eigen-decomposition of a similarity matrix and not the singular value decomposition (SVD) of the sample-by-abundance matrix. We propose a novel biplot that is based on an extension of the SVD, called the generalized matrix decomposition biplot (GMD-biplot), which involves an arbitrary matrix of similarities and the original matrix of variable measures, such as taxon abundances. As in a traditional biplot, points represent the samples, and arrows represent the variables. The proposed GMD-biplot is illustrated by analyzing multiple real and simulated data sets which demonstrate that the GMD-biplot provides improved clustering capability and a more meaningful relationship between the arrows and points.IMPORTANCE Biplots that simultaneously display the sample clustering and the important taxa have gained popularity in the exploratory analysis of human microbiome data. Traditional biplots, assuming Euclidean distances between samples, are not appropriate for microbiome data, when non-Euclidean distances are used to characterize dissimilarities among microbial communities. Thus, incorporating information from non-Euclidean distances into a biplot becomes useful for graphical displays of microbiome data. The proposed GMD-biplot accounts for any arbitrary non-Euclidean distances and provides a robust and computationally efficient approach for graphical visualization of microbiome data. In addition, the proposed GMD-biplot displays both the samples and taxa with respect to the same coordinate system, which further allows the configuration of future samples.}, }
@article {pmid31847455, year = {2019}, author = {Parida, S and Sharma, D}, title = {The Microbiome-Estrogen Connection and Breast Cancer Risk.}, journal = {Cells}, volume = {8}, number = {12}, pages = {}, pmid = {31847455}, issn = {2073-4409}, support = {R01 CA204555/CA/NCI NIH HHS/United States ; }, mesh = {Adiposity/physiology ; Breast Neoplasms/metabolism/*microbiology ; Dysbiosis/metabolism ; Estrogens/*metabolism ; Female ; Gastrointestinal Microbiome/physiology ; Humans ; Microbiota/*physiology ; Obesity/microbiology/physiopathology ; Risk Factors ; }, abstract = {The microbiome is undoubtedly the second genome of the human body and has diverse roles in health and disease. However, translational progress is limited due to the vastness of the microbiome, which accounts for over 3.3 million genes, whose functions are still unclear. Numerous studies in the past decade have demonstrated how microbiome impacts various organ-specific cancers by altering the energy balance of the body, increasing adiposity, synthesizing genotoxins and small signaling molecules, and priming and regulating immune response and metabolism of indigestible dietary components, xenobiotics, and pharmaceuticals. In relation to breast cancer, one of the most prominent roles of the human microbiome is the regulation of steroid hormone metabolism since endogenous estrogens are the most important risk factor in breast cancer development especially in postmenopausal women. Intestinal microbes encode enzymes capable of deconjugating conjugated estrogen metabolites marked for excretion, pushing them back into the enterohepatic circulation in a biologically active form. In addition, the intestinal microbes also break down otherwise indigestible dietary polyphenols to synthesize estrogen-like compounds or estrogen mimics that exhibit varied estrogenic potency. The present account discusses the potential role of gastrointestinal microbiome in breast cancer development by mediating metabolism of steroid hormones and synthesis of biologically active estrogen mimics.}, }
@article {pmid31844880, year = {2021}, author = {Jiang, S and Xiao, G and Koh, AY and Kim, J and Li, Q and Zhan, X}, title = {A Bayesian zero-inflated negative binomial regression model for the integrative analysis of microbiome data.}, journal = {Biostatistics (Oxford, England)}, volume = {22}, number = {3}, pages = {522-540}, pmid = {31844880}, issn = {1468-4357}, support = {//O'Donnell Brain Institute Pilot Award/ ; //Centers for Disease Control/National Center for Emerging and Zoonotic Infectious Diseases/ ; R01 AI123163/AI/NIAID NIH HHS/United States ; }, mesh = {Bacteria ; Bayes Theorem ; Humans ; *Microbiota ; Models, Statistical ; }, abstract = {Microbiome omics approaches can reveal intriguing relationships between the human microbiome and certain disease states. Along with identification of specific bacteria taxa associated with diseases, recent scientific advancements provide mounting evidence that metabolism, genetics, and environmental factors can all modulate these microbial effects. However, the current methods for integrating microbiome data and other covariates are severely lacking. Hence, we present an integrative Bayesian zero-inflated negative binomial regression model that can both distinguish differentially abundant taxa with distinct phenotypes and quantify covariate-taxa effects. Our model demonstrates good performance using simulated data. Furthermore, we successfully integrated microbiome taxonomies and metabolomics in two real microbiome datasets to provide biologically interpretable findings. In all, we proposed a novel integrative Bayesian regression model that features bacterial differential abundance analysis and microbiome-covariate effects quantifications, which makes it suitable for general microbiome studies.}, }
@article {pmid31832327, year = {2019}, author = {Ma, ZS and Li, W}, title = {How and Why Men and Women Differ in Their Microbiomes: Medical Ecology and Network Analyses of the Microgenderome.}, journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)}, volume = {6}, number = {23}, pages = {1902054}, pmid = {31832327}, issn = {2198-3844}, abstract = {Microgenderome or sexual dimorphism in microbiome refers to the bidirectional interactions between microbiotas, sex hormones, and immune systems, and it is highly relevant to disease susceptibility. A critical step in exploring microgenderome is to dissect the sex differences in key community ecology properties, which has not been systematically analyzed. This study aims at filling the gap by reanalyzing the Human Microbiome Project datasets with two objectives: (i) dissecting the sex differences in community diversity and their intersubject scaling, species composition, core/periphery species, and high-salience skeletons (species interactions); (ii) offering mechanistic interpretations for (i). Conceptually, the Vellend-Hanson synthesis of community ecology that stipulates selection, drift, speciation, and dispersal as the four processes driving community dynamics is followed. Methodologically, seven approaches reflecting the state-of-the-art research in medical ecology of human microbiomes are harnessed to achieve the objectives. It is postulated that the revealed microgenderome characteristics (categorized as seven aspects of differences/similarities) exert far reaching influences on disease susceptibility, and are primarily due to the sex difference in selection effects (deterministic fitness differences in microbial species and/or species interactions with each other or with their hosts), which are, in turn, shaped/modulated by host physiology (immunity, hormones, gut-brain communications, etc.).}, }
@article {pmid31828607, year = {2020}, author = {Berkes, E and Liao, YH and Neef, D and Grandalski, M and Monsul, N}, title = {Potentiated In Vitro Probiotic Activities of Lactobacillus fermentum LfQi6 Biofilm Biomass Versus Planktonic Culture.}, journal = {Probiotics and antimicrobial proteins}, volume = {12}, number = {3}, pages = {1097-1114}, pmid = {31828607}, issn = {1867-1314}, mesh = {*Antibiosis ; Biofilms/growth &amp; development ; Caco-2 Cells ; Humans ; *Limosilactobacillus fermentum/growth &amp; development/metabolism ; *Probiotics ; }, abstract = {In this study, we describe enhanced in vitro probiotic activities of preformed biofilms versus planktonic cultures of Lactobacillus fermentum LfQi6 (LfQi6), a lactic acid bacterium (LAB) isolated from the human microbiome. These evaluations are used to help predict host in vivo probiotic benefits and therefore indicate that LfQi6 may provide significant probiotic benefits in the human host when administered as preformed biofilms rather than as planktonic cultures. Specifically, LfQi6 biofilms demonstrated improved in vitro performance versus LfQi6 planktonic cultures for host gastrointestinal survival and engraftment, strain-specific antimicrobial and anti-biofilm activity against clinically significant pathogens, concurrent promotion of beneficial gastrointestinal commensal biofilms, beneficial commensal enzyme activities, and host cellular-protective glutathione antioxidant activity. Evaluation of LfQi6 according to the European Food Safety Authority (EFSA 2007, 2012, 2015) Guidelines and Joint FAO/WHO Expert Consultation on Evaluation of Health and Nutritional Properties of Probiotics in Food Evaluation of Probiotics in Food (FAO/WHO, 2002) demonstrates strain safety. In summary, in vitro evaluation of Lact. fermentum LfQi6 demonstrates significant evidence for strain-specific probiotic characteristics and safety. Moreover, strain-specific as well as biofilm-phenotype-specific benefits demonstrated in vitro furthermore suggest that in vivo use of LfQi6 biofilm biomass may be of greater benefit to the human host than the use of standard planktonic cultures. This concept - potentiating probiotic benefits through the use of preformed commensal biofilms - is novel and may serve to further broaden the application of microbial biofilms to human health.}, }
@article {pmid31827811, year = {2019}, author = {Rapp, R}, title = {On mycohuman performances: fungi in current artistic research.}, journal = {Fungal biology and biotechnology}, volume = {6}, number = {}, pages = {22}, doi = {10.1186/s40694-019-0085-6}, pmid = {31827811}, issn = {2054-3085}, abstract = {This review reflects several artists and their artistic research in the field of hybrid art, bio art, or science art, working with Fungi as both subject matter and medium. The work of Saša Spačal, Tarsh Bates and Theresa Schubert is not representational in the manner of traditional fine art, but works rather through performative, multidisciplinary and research-based strategies to produce artwork through fungal material as such. My research results are based on the series "Nonhuman subjectivities" and "Nonhuman agents" that Christian de Lutz and I conceived and realized at Art Laboratory Berlin (2016-18) in various formats-exhibitions, workshops, lectures and a conference. The work of Saša Spačal and her colleagues involves creating interactive situations of symbiosis between the fungal and the human. An example of this is Myconnect, in which a biofeedback loop is related between the human participant and Oyster mushroom mycelia through a special encounter, which is mediated by non-linguistic forms of awareness and exchange-sonic, electronic and metabolic. Tarsh Bates' work with Candida albicans and Candida parapsilosis refers to a complex and intimate relation between the human and yeasts that form part of the human microbiome. Bates considers the relationship between humans and yeast as "CandidaHomo Ecologies" and sees both partners as equals. She explores this relationship through her work The Surface dynamics of adhesion, examines it from historical and metabolic levels through an installation that includes the live yeast growing on agar mixed with the artist's own blood. Theresa Schubert's installations and site-specific interventions treat living organisms, especially Fungi, as collaborators and co-creators. Her work Growing Geometries-Tattooing Mushrooms follows the morphological development of fungal fruiting bodies through the intervention of a tattoo. Her performative forest walks, especially the Forestal Psyche and also new actions for the "Mind the Fungi" project, engage the public in an intimate and multi sensory encounter with Fungi and their surrounding environment.}, }
@article {pmid31824656, year = {2019}, author = {Barton, W and O'Sullivan, O and Cotter, PD}, title = {Metabolic phenotyping of the human microbiome.}, journal = {F1000Research}, volume = {8}, number = {}, pages = {}, pmid = {31824656}, issn = {2046-1402}, mesh = {Humans ; Metabolomics ; *Microbiota ; }, abstract = {The human microbiome has been identified as having a key role in health and numerous diseases. Trillions of microbial cells and viral particles comprise the microbiome, each representing modifiable working elements of an intricate bioactive ecosystem. The significance of the human microbiome as it relates to human biology has progressed through culture-dependent (for example, media-based methods) and, more recently, molecular (for example, genetic sequencing and metabolomic analysis) techniques. The latter have become increasingly popular and evolved from being used for taxonomic identification of microbiota to elucidation of functional capacity (sequencing) and metabolic activity (metabolomics). This review summarises key elements of the human microbiome and its metabolic capabilities within the context of health and disease.}, }
@article {pmid31824493, year = {2019}, author = {Michel-Todó, L and Reche, PA and Bigey, P and Pinazo, MJ and Gascón, J and Alonso-Padilla, J}, title = {In silico Design of an Epitope-Based Vaccine Ensemble for Chagas Disease.}, journal = {Frontiers in immunology}, volume = {10}, number = {}, pages = {2698}, pmid = {31824493}, issn = {1664-3224}, mesh = {Antigens, Protozoan/*immunology ; Chagas Disease/immunology/*prevention &amp; control ; Computer Simulation ; Drug Design ; Epitopes, B-Lymphocyte/*immunology ; Epitopes, T-Lymphocyte/*immunology ; Humans ; Protozoan Vaccines/*immunology ; }, abstract = {Trypanosoma cruzi infection causes Chagas disease, which affects 7 million people worldwide. Two drugs are available to treat it: benznidazole and nifurtimox. Although both are efficacious against the acute stage of the disease, this is usually asymptomatic and goes undiagnosed and untreated. Diagnosis is achieved at the chronic stage, when life-threatening heart and/or gut tissue disruptions occur in ~30% of those chronically infected. By then, the drugs' efficacy is reduced, but not their associated high toxicity. Given current deficiencies in diagnosis and treatment, a vaccine to prevent infection and/or the development of symptoms would be a breakthrough in the management of the disease. Current vaccine candidates are mostly based on the delivery of single antigens or a few different antigens. Nevertheless, due to the high biological complexity of the parasite, targeting as many antigens as possible would be desirable. In this regard, an epitope-based vaccine design could be a well-suited approach. With this aim, we have gone through publicly available databases to identify T. cruzi epitopes from several antigens. By means of a computer-aided strategy, we have prioritized a set of epitopes based on sequence conservation criteria, projected population coverage of Latin American population, and biological features of their antigens of origin. Fruit of this analysis, we provide a selection of CD8[+] T cell, CD4[+] T cell, and B cell epitopes that have <70% identity to human or human microbiome protein sequences and represent the basis toward the development of an epitope-based vaccine against T. cruzi.}, }
@article {pmid31824463, year = {2019}, author = {Freitag, TL and Hartikainen, A and Jouhten, H and Sahl, C and Meri, S and Anttila, VJ and Mattila, E and Arkkila, P and Jalanka, J and Satokari, R}, title = {Minor Effect of Antibiotic Pre-treatment on the Engraftment of Donor Microbiota in Fecal Transplantation in Mice.}, journal = {Frontiers in microbiology}, volume = {10}, number = {}, pages = {2685}, pmid = {31824463}, issn = {1664-302X}, abstract = {Fecal microbiota transplantation (FMT) is an effective therapy for recurrent Clostridioides difficile infection (rCDI) and is also considered a potential treatment for a wide range of intestinal and systemic diseases. FMT corrects the microbial dysbiosis associated with rCDI, and the engraftment of donor microbiota is likely to play a key role in treatment efficacy. For disease indications other than rCDI, FMT treatment efficacy has been moderate. This may be partly due to stronger resilience of resident host microbiota in patients who do not suffer from rCDI. In rCDI, patients typically have undergone several antibiotic treatments prior to FMT, depleting the microbiota. In this study, we addressed the effect of broad-spectrum antibiotics (Ab) as a pre-treatment to FMT on the engraftment of donor microbiota in recipients. We conducted a pre-clinical study of FMT between two healthy mouse strains, Balb/c as donors and C57BL/6 as recipients, to perform FMT within the same species and to mimic interindividual FMT between human donors and patients. Microbiota composition was assessed with high-throughput 16S rDNA amplicon sequencing. The microbiota of Balb/c and C57BL/6 mice differed significantly, which allowed for the assessment of microbiota transplantation from the donor strain to the recipient. Our results showed that Ab-treatment depleted microbiota in C57BL/6 recipient mice prior to FMT. The diversity of microbiota did not recover spontaneously to baseline levels during 8 weeks after Ab-treatment, but was restored already at 2 weeks in mice receiving FMT. Interestingly, pre-treatment with antibiotics prior to FMT did not increase the overall similarity of the recipient's microbiota to that of the donor's, as compared with mice receiving FMT without Ab-treatment. Pre-treatment with Ab improved the establishment of only a few donor-derived taxa, such as Bifidobacterium, in the recipients, thus having a minor effect on the engraftment of donor microbiota in FMT. In conclusion, pre-treatment with broad-spectrum antibiotics did not improve the overall engraftment of donor microbiota, but did improve the engraftment of specific taxa. These results may inform future therapeutic studies of FMT.}, }
@article {pmid31821833, year = {2020}, author = {Golofast, B and Vales, K}, title = {The connection between microbiome and schizophrenia.}, journal = {Neuroscience and biobehavioral reviews}, volume = {108}, number = {}, pages = {712-731}, doi = {10.1016/j.neubiorev.2019.12.011}, pmid = {31821833}, issn = {1873-7528}, mesh = {Animals ; Cesarean Section/*adverse effects ; *Dysbiosis/etiology/immunology/microbiology ; Female ; Humans ; *Inflammation/diet therapy/immunology/microbiology ; *Microbiota/immunology ; Pregnancy ; *Prenatal Exposure Delayed Effects/immunology/microbiology ; Probiotics/*therapeutic use ; *Schizophrenia/diet therapy/immunology/microbiology ; }, abstract = {There has been an accumulation of knowledge about the human microbiome, some detailed investigations of the gastrointestinal microbiota and its functions, and the highlighting of complex interactions between the gut, the gut microbiota, and the central nervous system. That assumes the involvement of the microbiome in the pathogenesis of various CNS diseases, including schizophrenia. Given this information and the fact, that the gut microbiota is sensitive to internal and environmental influences, we have speculated that among the factors that influence the formation and composition of gut microbiota during life, possible key elements in the schizophrenia development chain are hidden where gut microbiota is a linking component. This article aims to describe and understand the developmental relationships between intestinal microbiota and the risk of developing schizophrenia.}, }
@article {pmid31812808, year = {2019}, author = {Hall, CV and Lord, A and Betzel, R and Zakrzewski, M and Simms, LA and Zalesky, A and Radford-Smith, G and Cocchi, L}, title = {Co-existence of Network Architectures Supporting the Human Gut Microbiome.}, journal = {iScience}, volume = {22}, number = {}, pages = {380-391}, pmid = {31812808}, issn = {2589-0042}, abstract = {Microbial organisms of the human gut microbiome do not exist in isolation but form complex and diverse interactions to maintain health and reduce risk of disease development. The organization of the gut microbiome is assumed to be a singular assortative network, where interactions between operational taxonomic units (OTUs) can readily be clustered into segregated and distinct communities. Here, we leverage recent methodological advances in network modeling to assess whether communities in the human microbiome exhibit a single network structure or whether co-existing mesoscale network architectures are present. We found evidence for core-periphery structures in the microbiome, supported by strong, assortative community interactions. This complex architecture, coupled with previously reported functional roles of OTUs, provides a nuanced understanding of how the microbiome simultaneously promotes high microbial diversity and maintains functional redundancy.}, }
@article {pmid31812180, year = {2019}, author = {Borbet, TC and Zhang, X and Müller, A and Blaser, MJ}, title = {The role of the changing human microbiome in the asthma pandemic.}, journal = {The Journal of allergy and clinical immunology}, volume = {144}, number = {6}, pages = {1457-1466}, pmid = {31812180}, issn = {1097-6825}, support = {TL1 TR001447/TR/NCATS NIH HHS/United States ; U01 AI122285/AI/NIAID NIH HHS/United States ; }, mesh = {Allergens/immunology ; *Asthma/epidemiology/immunology/microbiology ; Disease Susceptibility/immunology/microbiology ; Helicobacter pylori/immunology ; Humans ; Microbiota/*immunology ; Pandemics ; Risk Factors ; }, abstract = {Asthma and allergy incidence continue to increase globally. We have made significant strides in treating disease, but it is becoming more apparent that we need to advance our knowledge into the origins of asthmatic disease. Much recent work has indicated that microbiome composition influences immune regulation and that multiple health care factors have driven a loss in microbiome diversity in modern human populations. Evidence is growing of microbiota-driven influences on immune development, asthma susceptibility, and asthma pathogenesis. The focus of this review is to highlight the strides the field has made in characterizing the constituents of the human gastrointestinal microbiota, such as Helicobacter pylori, other members of the neonatal intestinal microbiota, and microbial peptides and metabolites that influence host immunity and immune response to allergens. As we delve further into this field of research, the goal will be to find actionable and clinical interventions to identify at-risk populations earlier to prevent disease onset. Manipulation of the host microbial community during infancy might be an especially promising approach.}, }
@article {pmid31812098, year = {2020}, author = {Neckovic, A and van Oorschot, RAH and Szkuta, B and Durdle, A}, title = {Investigation of direct and indirect transfer of microbiomes between individuals.}, journal = {Forensic science international. Genetics}, volume = {45}, number = {}, pages = {102212}, doi = {10.1016/j.fsigen.2019.102212}, pmid = {31812098}, issn = {1878-0326}, mesh = {DNA, Bacterial/genetics ; Forensic Genetics/methods ; Glass ; Humans ; Microbiota/*genetics ; Paper ; Phylogeny ; Principal Component Analysis ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; Skin/*microbiology ; Textiles ; *Touch ; }, abstract = {The human microbiome encompasses the fungi, bacteria and viruses that live on, within, and immediately surrounding the body. Microbiomes have potential utility in forensic science as an evidentiary tool to link or exclude persons of interest associated with criminal activities. Research has shown the microbiome is individualised, and that personal microbial signatures can be recovered from surfaces such as phones, shoes and fabrics. Before the human microbiome may be used as an investigative tool, further research is required to investigate the utility and potential limitations surrounding microbial profiling. This includes the detectability of microbial transfer between individuals or items, the associated risks (such as contamination events) and the applicability of microbial profiling for forensic purposes. This research aimed to identify whether an individual's distinguishable microbiome could be transferred to another individual and onto substrates, and vice versa. Paper, cotton, and glass surfaces were chosen to represent a range of substrate matrices. The study involved six participants placed into three pairs; participants took part in two modes of transfer. Transfer Mode 1 involved the pair shaking hands, followed by rubbing a substrate in their right hand. Transfer Mode 2 involved individuals rubbing a substrate in their left hand, swapping substrates with their partner and then rubbing the swapped substrate in their left hand. 16S rRNA sequencing was performed on the extracted microbial DNA from participant and substrate samples. Quantitative Insights into Microbial Ecology 2 (QIIME 2) was used for sequence quality control and beta (between-sample) diversity analyses and taxonomic assignment. Principal Coordinate Analysis (PCoA) based on Jaccard distances was visualised through Emperor software to determine the phylogenetic similarity of bacterial communities between participants and among participant pairs. Statistical testing through PERMANOVA revealed significant differences in the Jaccard distances between each participant pair (P < 0.001), highlighting not only the potential distinguishability of skin microbiomes among individuals, but also the clustering effect observed between participant pairs due to the potential transfer of hand-associated microbiomes between individuals. The study demonstrated that transfer of the human skin microbiome had occurred between all participant pairs, regardless of substrate type or mode of transfer.}, }
@article {pmid31802114, year = {2020}, author = {Barrera-Vázquez, OS and Gomez-Verjan, JC}, title = {The Unexplored World of Human Virome, Mycobiome, and Archaeome in Aging.}, journal = {The journals of gerontology. Series A, Biological sciences and medical sciences}, volume = {75}, number = {10}, pages = {1834-1837}, doi = {10.1093/gerona/glz274}, pmid = {31802114}, issn = {1758-535X}, mesh = {*Aging ; *Archaea ; Humans ; *Microbiota ; Mycobiome ; Phylogeny ; Virome ; }, abstract = {In the last decades, improvements in different aspects of sanitation, medical care, and nutrition, among others, have permitted an increase in the average lifespan of human population around the world. These advances have stimulated an increased interest in the study of the aging process and age-sensitive characteristics, such as the microbial community that colonizes the human body (microbiome). The human microbiome is composed of bacteria (bacteriome), archaea (archaeome), fungi (mycobiome), and viruses (virome). To date, research has mainly been centered on the composition of the bacteriome, with other members remain poorly studied. Interestingly, changes in the composition of the microbiome have been implicated in aging and age-related diseases. Therefore, in the present perspective, we suggest expanding the scope to research to include the role and the possible associations that the other members of the microbiome could have in the aging organism. An expanded view of the microbiome would increase our knowledge of the physiology of aging and may be particularly valuable for the treatment and diagnosis of age-related diseases.}, }
@article {pmid31795231, year = {2019}, author = {Leon-Velarde, CG and Jun, JW and Skurnik, M}, title = {Yersinia Phages and Food Safety.}, journal = {Viruses}, volume = {11}, number = {12}, pages = {}, pmid = {31795231}, issn = {1999-4915}, mesh = {Animals ; Bacteriophages/*physiology ; *Food Microbiology ; *Food Safety ; Humans ; Yersinia Infections/*microbiology ; Yersinia enterocolitica/isolation &amp; purification/*virology ; }, abstract = {One of the human- and animal-pathogenic species in genus Yersinia is Yersinia enterocolitica, a food-borne zoonotic pathogen that causes enteric infections, mesenteric lymphadenitis, and sometimes sequelae such as reactive arthritis and erythema nodosum. Y. enterocolitica is able to proliferate at 4 C, making it dangerous if contaminated food products are stored under refrigeration. The most common source of Y. enterocolitica is raw pork meat. Microbiological detection of the bacteria from food products is hampered by its slow growth rate as other bacteria overgrow it. Bacteriophages can be exploited in several ways to increase food safety with regards to contamination by Y. enterocolitica. For example, Yersinia phages could be useful in keeping the contamination of food products under control, or, alternatively, the specificity of the phages could be exploited in developing rapid and sensitive diagnostic tools for the identification of the bacteria in food products. In this review, we will discuss the present state of the research on these topics.}, }
@article {pmid31790791, year = {2020}, author = {Ahmed, N and Daniel, B and Varghese, J and Evangeline, R and Jose, T}, title = {Oropharyngeal microbiome of an HIV-positive patient.}, journal = {Microbial pathogenesis}, volume = {139}, number = {}, pages = {103805}, doi = {10.1016/j.micpath.2019.103805}, pmid = {31790791}, issn = {1096-1208}, mesh = {Bacteroides/isolation &amp; purification/metabolism ; Clostridium/isolation &amp; purification/metabolism ; DNA, Bacterial/genetics/isolation &amp; purification ; Enterococcus/isolation &amp; purification/metabolism ; Gastrointestinal Microbiome ; HIV Infections/*microbiology ; High-Throughput Nucleotide Sequencing ; Humans ; *Microbiota ; Micrococcus/isolation &amp; purification/metabolism ; Oropharynx/*microbiology ; Pharynx/microbiology ; Phylogeny ; Prevotella/isolation &amp; purification/metabolism ; Proteus/isolation &amp; purification/metabolism ; RNA, Ribosomal, 16S/genetics/isolation &amp; purification ; Respiratory System/metabolism/microbiology ; Respiratory Tract Infections/microbiology ; Sequence Analysis, DNA ; }, abstract = {Studies on understanding the human microbiome continue to grow rapidly; nonetheless, reports on alterations in the microbiome post HIV infection are limited. Human microbiome is an aggregate of bacteria, fungi, viruses and archaea that have co-evolved with humans. These microbes have important roles in immune modulation, vitamin synthesis, metabolism etc. The human pharyngeal microbiome, which resides in the junction between digestive and respiratory tracts, might have a key role in the prevention of respiratory tract infections, akin to the actions of the intestinal microbiome against enteric infections. The respiratory tract is constantly exposed to various environmental and endogenous microbes; however, unlike other similar mucosal surfaces, there has been limited investigation of the microbiome of the respiratory tract. HIV infection is associated with alterations in the respiratory microbiome. The aim of this study was to use next-generation sequencing to determine the composition of the oropharyngeal microbiome in a HIV-positive individual. The bacterial composition was determined by illumina sequencing using MiSeq of partial 16S rRNA genes (V3-V4). A total of 3, 57,926 reads were analyzed. Overall, the genera Proteus, Enterococcus, Bacteroides, Prevotella and Clostridium were most prevalent bacterial populations in the oropharynx of an HIV positive patient.}, }
@article {pmid31782749, year = {2019}, author = {Quagliariello, A and Di Paola, M and De Fanti, S and Gnecchi-Ruscone, GA and Martinez-Priego, L and Pérez-Villaroya, D and Sherpa, MG and Sherpa, PT and Marinelli, G and Natali, L and Di Marcello, M and Peluzzi, D and Di Cosimo, P and D'Auria, G and Pettener, D and Sazzini, M and Luiselli, D and De Filippo, C}, title = {Gut microbiota composition in Himalayan and Andean populations and its relationship with diet, lifestyle and adaptation to the high-altitude environment.}, journal = {Journal of anthropological sciences = Rivista di antropologia : JASS}, volume = {96}, number = {}, pages = {189-208}, doi = {10.4436/JASS.97007}, pmid = {31782749}, issn = {2037-0644}, mesh = {Adaptation, Physiological/*physiology ; Adult ; Altitude ; Biological Evolution ; Bolivia/ethnology ; Diet/*statistics &amp; numerical data ; Female ; Gastrointestinal Microbiome/*physiology ; Humans ; Life Style/*ethnology ; Male ; Mountaineering/*physiology ; Nepal/ethnology ; Young Adult ; }, abstract = {Human populations living at high altitude evolved a number of biological adjustments to cope with a challenging environment characterised especially by reduced oxygen availability and limited nutritional resources. This condition may also affect their gut microbiota composition. Here, we explored the impact of exposure to such selective pressures on human gut microbiota by considering different ethnic groups living at variable degrees of altitude: the high-altitude Sherpa and low-altitude Tamang populations from Nepal, the high-altitude Aymara population from Bolivia, as well as a low-altitude cohort of European ancestry, used as control. We thus observed microbial profiles common to the Sherpa and Aymara, but absent in the low-altitude cohorts, which may contribute to the achievement of adaptation to high-altitude lifestyle and nutritional conditions. The collected evidences suggest that microbial signatures associated to these rural populations may enhance metabolic functions able to supply essential compounds useful for the host to cope with high altitude-related physiological changes and energy demand. Therefore, these results add another valuable piece of the puzzle to the understanding of the beneficial effects of symbiosis between microbes and their human host even from an evolutionary perspective.}, }
@article {pmid31781817, year = {2020}, author = {Bajerski, F and Bürger, A and Glasmacher, B and Keller, ERJ and Müller, K and Mühldorfer, K and Nagel, M and Rüdel, H and Müller, T and Schenkel, J and Overmann, J}, title = {Factors determining microbial colonization of liquid nitrogen storage tanks used for archiving biological samples.}, journal = {Applied microbiology and biotechnology}, volume = {104}, number = {1}, pages = {131-144}, pmid = {31781817}, issn = {1432-0614}, support = {GDK//GDK Gemeinschaft Deutscher Kryobanken/ ; FP7-HEALTH-F4-2010-261492//Helmholtz-Gemeinschaft/ ; ExNet-0041-Phase2-3//Helmholtz-Gemeinschaft/ ; }, mesh = {Bacteria/genetics ; Bacterial Load ; Biological Specimen Banks/*standards ; Cryopreservation/*instrumentation ; DNA, Bacterial/genetics ; *Equipment Contamination ; Fungi/genetics ; Humans ; Ice ; Limit of Detection ; *Nitrogen ; RNA, Ribosomal, 16S ; }, abstract = {The availability of bioresources is a precondition for life science research, medical applications, and diagnostics, but requires a dedicated quality management to guarantee reliable and safe storage. Anecdotal reports of bacterial isolates and sample contamination indicate that organisms may persist in liquid nitrogen (LN) storage tanks. To evaluate the safety status of cryocollections, we systematically screened organisms in the LN phase and in ice layers covering inner surfaces of storage tanks maintained in different biobanking facilities. We applied a culture-independent approach combining cell detection by epifluorescence microscopy with the amplification of group-specific marker genes and high-throughput sequencing of bacterial ribosomal genes. In the LN phase, neither cells nor bacterial 16S rRNA gene copy numbers were detectable (detection limit, 10[2] cells per ml, 10[3] gene copies per ml). In several cases, small numbers of bacteria of up to 10[4] cells per ml and up to 10[6] gene copies per ml, as well as Mycoplasma, or fungi were detected in the ice phase formed underneath the lids or accumulated at the bottom. The bacteria most likely originated from the stored materials themselves (Elizabethingia, Janthibacterium), the technical environment (Pseudomonas, Acinetobacter, Methylobacterium), or the human microbiome (Bacteroides, Streptococcus, Staphylococcus). In single cases, bacteria, Mycoplasma, fungi, and human cells were detected in the debris at the bottom of the storage tanks. In conclusion, the limited microbial load of the ice phase and in the debris of storage tanks can be effectively avoided by minimizing ice formation and by employing hermetically sealed sample containers.}, }
@article {pmid31780826, year = {2019}, author = {Tang, L}, title = {Exploring the chemical space of the human microbiome.}, journal = {Nature methods}, volume = {16}, number = {12}, pages = {1201}, doi = {10.1038/s41592-019-0671-9}, pmid = {31780826}, issn = {1548-7105}, mesh = {Humans ; Metagenome ; *Microbiota ; }, }
@article {pmid31780057, year = {2020}, author = {Garud, NR and Pollard, KS}, title = {Population Genetics in the Human Microbiome.}, journal = {Trends in genetics : TIG}, volume = {36}, number = {1}, pages = {53-67}, doi = {10.1016/j.tig.2019.10.010}, pmid = {31780057}, issn = {0168-9525}, mesh = {Bacteria/classification/genetics/metabolism ; Gastrointestinal Microbiome/*genetics ; Genetic Variation/*genetics ; *Genetics, Population ; Humans ; Metagenome/genetics ; Metagenomics/trends ; Microbiota/*genetics ; }, abstract = {While the human microbiome's structure and function have been extensively studied, its within-species genetic diversity is less well understood. However, genetic mutations in the microbiome can confer biomedically relevant traits, such as the ability to extract nutrients from food, metabolize drugs, evade antibiotics, and communicate with the host immune system. The population genetic processes by which these traits evolve are complex, in part due to interacting ecological and evolutionary forces in the microbiome. Advances in metagenomic sequencing, coupled with bioinformatics tools and population genetic models, facilitate quantification of microbiome genetic variation and inferences about how this diversity arises, evolves, and correlates with traits of both microbes and hosts. In this review, we explore the population genetic forces (mutation, recombination, drift, and selection) that shape microbiome genetic diversity within and between hosts, as well as efforts towards predictive models that leverage microbiome genetics.}, }
@article {pmid31775543, year = {2020}, author = {Poon, WL and Lee, JC and Leung, KS and Alenius, H and El-Nezami, H and Karisola, P}, title = {Nanosized silver, but not titanium dioxide or zinc oxide, enhances oxidative stress and inflammatory response by inducing 5-HETE activation in THP-1 cells.}, journal = {Nanotoxicology}, volume = {14}, number = {4}, pages = {453-467}, doi = {10.1080/17435390.2019.1687776}, pmid = {31775543}, issn = {1743-5404}, mesh = {Antioxidants/metabolism ; Glutathione/metabolism ; Humans ; Hydroxyeicosatetraenoic Acids/*metabolism ; Inflammation ; Metal Nanoparticles/*toxicity ; Mitochondria/drug effects/metabolism ; Oxidative Stress/*drug effects/immunology ; Silver/*toxicity ; THP-1 Cells ; Titanium/*toxicity ; Zinc Oxide/*toxicity ; }, abstract = {Bioactive, oxygenated metabolites of polyunsaturated fatty acids (PUFAs) are important indicators of inflammation and oxidative stress but almost nothing is known about their interactions with nanomaterials (NMs). To investigate the effects of nano-sized materials (n-TiO2, n-ZnO, n-Ag) and their bulk-sized or ionic (b-TiO2, b-ZnO, i-Ag) counterpart, we studied the status of oxidative stress and PUFA metabolism in THP-1 cells at low-toxic concentrations (<15% cytotoxicity) 6 h or 24 h after the particle exposures by LC/MS and microarray. N-Ag had a significant and sustained impact on cellular antioxidant defense, seen as incremental synthesis and accumulation of glutathione (GSH) in the cell, and reduction of superoxide dismutase (SOD) activity. The cellular particle doses were largely dependent on exposure duration and particle dissolution, and active transporter mechanisms controlled the concentration of Zn in cytosol. Even at these sub-toxic concentrations, n-Ag was able to induce statistically significant elevation in the 5-HETE: arachidonic acid ratio at 24 h, which suggests association to oxidative stress and induction of pro-inflammatory responses. This was supported by the enhanced gene expression of chemotaxis-related genes. Overall, THP-1 cells internalized all tested particles, but only n-Ag led to low level of oxidative stress through ROS production and antioxidant balance disruption. N-Ag stimulated arachidonic acid oxidation to form 5-HETE which further magnified the inflammatory responses by enhancing the production of mitochondrial superoxide and leukocyte chemokines. Since the sustained n-Ag uptake was detected, the effects may last long and function as a trigger for the low-grade inflammation playing role in the chronic inflammatory diseases.}, }
@article {pmid31753125, year = {2019}, author = {Croitoru, DO and Piguet, V}, title = {A Mother's Touch: Emerging Roles in Development of the Cutaneous Microbiome.}, journal = {The Journal of investigative dermatology}, volume = {139}, number = {12}, pages = {2414-2416}, doi = {10.1016/j.jid.2019.06.144}, pmid = {31753125}, issn = {1523-1747}, mesh = {Child ; Female ; Humans ; Infant ; *Microbiota ; *Mothers ; Skin ; Touch ; }, abstract = {Skin-associated bacteria constitute a large proportion of the human microbiome and influence host immunity. The healthy cutaneous microbiome adopts site-specific composition, weeks to months postpartum. Zhu et al. (2019) expand the scope of pediatric data, tracking infant skin microflora changes by site, through childhood, and establish new associations with delivery mode and maternal microbiome.}, }
@article {pmid31752095, year = {2019}, author = {Ristori, MV and Quagliariello, A and Reddel, S and Ianiro, G and Vicari, S and Gasbarrini, A and Putignani, L}, title = {Autism, Gastrointestinal Symptoms and Modulation of Gut Microbiota by Nutritional Interventions.}, journal = {Nutrients}, volume = {11}, number = {11}, pages = {}, pmid = {31752095}, issn = {2072-6643}, mesh = {Autism Spectrum Disorder/*complications/*diet therapy ; Child ; *Child Nutritional Physiological Phenomena ; Child, Preschool ; Diet/classification ; Fatty Acids, Volatile/metabolism ; Food Preferences ; Gastrointestinal Diseases/*complications/*microbiology ; *Gastrointestinal Microbiome ; Humans ; Neurotransmitter Agents/metabolism ; Nutritional Status ; Serotonin/metabolism ; }, abstract = {Autism spectrum disorder (ASD) is a complex behavioral syndrome that is characterized by speech and language disorders, intellectual impairment, learning and motor dysfunctions. Several genetic and environmental factors are suspected to affect the ASD phenotype including air pollution, exposure to pesticides, maternal infections, inflammatory conditions, dietary factors or consumption of antibiotics during pregnancy. Many children with ASD shows abnormalities in gastrointestinal (GI) physiology, including increased intestinal permeability, overall microbiota alterations, and gut infection. Moreover, they are "picky eaters" and the existence of specific sensory patterns in ASD patients could represent one of the main aspects in hampering feeding. GI disorders are associated with an altered composition of the gut microbiota. Gut microbiome is able to communicate with brain activities through microbiota-derived signaling molecules, immune mediators, gut hormones as well as vagal and spinal afferent neurons. Since the diet induces changes in the intestinal microbiota and in the production of molecules, such as the SCFA, we wanted to investigate the role that nutritional intervention can have on GI microbiota composition and thus on its influence on behavior, GI symptoms and microbiota composition and report which are the beneficial effect on ASD conditions.}, }
@article {pmid31744921, year = {2019}, author = {Estrela, AB and Nakashige, TG and Lemetre, C and Woodworth, ID and Weisman, JL and Cohen, LJ and Brady, SF}, title = {Functional Multigenomic Screening of Human-Associated Bacteria for NF-κB-Inducing Bioactive Effectors.}, journal = {mBio}, volume = {10}, number = {6}, pages = {}, pmid = {31744921}, issn = {2150-7511}, support = {R01 AT009562/AT/NCCIH NIH HHS/United States ; }, mesh = {Bacteria/*genetics ; Bacterial Infections/*metabolism/*microbiology ; Gene Expression Regulation, Bacterial ; Gene Library ; *Genome, Bacterial ; Humans ; *Metagenomics/methods ; Microbiota ; NF-kappa B/*metabolism ; Operon ; Phylogeny ; }, abstract = {The effect of the microbiota on its human host is driven, at least in part, by small-molecule and protein effectors it produces. Here, we report on the use of functional multigenomic screening to identify microbiota-encoded effectors. In this study, genomic DNA from 116 human-associated bacteria was cloned en masse, and the resulting multigenomic library was screened using a nuclear factor-κB reporter (NF-κB) assay. Functional multigenomics builds on the concept of functional metagenomics but takes advantage of increasing advances in cultivating and sequencing human-associated bacteria. Effector genes found to confer NF-κB-inducing activity to Escherichia coli encode proteins in four general categories: cell wall hydrolases, membrane transporters, lipopolysaccharide biosynthetic enzymes, and proteins of unknown function. The compact nature of multigenomic libraries, which results from the ability to normalize input DNA ratios, should simplify screening of libraries using diverse heterologous hosts and reporter assays, increasing the rate of discovery of novel effector genes.IMPORTANCE Human-associated bacteria are thought to encode bioactive small molecules and proteins that play an intimate role in human health and disease. Here, we report on the creation and functional screening of a multigenomic library constructed using genomic DNA from 116 bacteria found at diverse sites across the human body. Individual clones were screened for genes capable of conferring NF-κB-inducing activity to Escherichia coli NF-κB is a useful reporter for a range of cellular processes related to immunity, pathogenesis, and inflammation. Compared to the screening of metagenomic libraries, the ability to normalize input DNA ratios when constructing a multigenomic library should facilitate the more efficient examination of commensal bacteria for diverse bioactivities. Multigenomic screening takes advantage of the growing available resources in culturing and sequencing the human microbiota and generates starting points for more in-depth studies on the mechanisms by which commensal bacteria interact with their human host.}, }
@article {pmid31744351, year = {2021}, author = {Bender, JM and Li, F and Purswani, H and Capretz, T and Cerini, C and Zabih, S and Hung, L and Francis, N and Chin, S and Pannaraj, PS and Aldrovandi, G}, title = {Early exposure to antibiotics in the neonatal intensive care unit alters the taxonomic and functional infant gut microbiome.}, journal = {The journal of maternal-fetal &amp; neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians}, volume = {34}, number = {20}, pages = {3335-3343}, pmid = {31744351}, issn = {1476-4954}, support = {K12 HD052954/HD/NICHD NIH HHS/United States ; }, mesh = {Anti-Bacterial Agents ; Dysbiosis ; Feces ; *Gastrointestinal Microbiome ; Humans ; Infant ; Infant, Newborn ; Intensive Care Units, Neonatal ; }, abstract = {INTRODUCTION: The infant gut microbiome is thought to play a key role in developing metabolic and immunologic pathways. Antibiotics have been shown to disrupt the human microbiome, but the impact they have on infants during this key window of development remains poorly understood. Through this study, we further characterize the effect antibiotics have on the gut microbiome of infants by looking at metagenomic sequencing data over time.<br><br>MATERIALS AND METHODS: Stool samples were collected on infants from a large tertiary care neonatal intensive care unit. After DNA extraction, metagenomics libraries were generated and sequenced. Taxonomic and functional analyses were then performed. Further directed specimen sequencing for fungal species was also performed.<br><br>RESULTS: A total of 51 stool samples from 25 infants were analyzed: seven infants were on antibiotics during at least one of their collection time points. Antibiotics given at birth altered the microbiome (PERMANOVA R[2]&#x2009;= 0.044, p&#x2009;=&#x2009;.002) but later courses did not (R[2]&#x2009;=&#x2009;0.023, p&#x2009;=&#x2009;.114). Longitudinal samples collected while off antibiotics were more similar than those collected during a transition on or off antibiotics (mean Bray-Curtis distance 0.29 vs. 0.63, Wilcoxon p&#x2009;=&#x2009;.06). Functional analysis revealed four microbial pathways that were disrupted by antibiotics given at-birth (p&#x2009;<&#x2009;.1, folate synthesis, glycerolipid metabolism, fatty acid biosynthesis, and glycolysis). No functional changes associated with current antibiotic use were identified. In a limited sample set, we saw little evidence of fungal involvement in the overall infant microbiome.<br><br>CONCLUSION: Through this study, we have further characterized the role antibiotics have in the development of the infant microbiome. Antibiotics given at birth were associated with alterations in the microbiome and had significant impact on the functional pathways involved in folate synthesis and multiple metabolic pathways. Later courses of antibiotics led to stochastic dysbiosis and a significant decrease in Escherichia coli. Further characterization of the infant mycobiome is still needed.}, }
@article {pmid31739448, year = {2019}, author = {Mohanraj, U and Wan, X and Spruit, CM and Skurnik, M and Pajunen, MI}, title = {A Toxicity Screening Approach to Identify Bacteriophage-Encoded Anti-Microbial Proteins.}, journal = {Viruses}, volume = {11}, number = {11}, pages = {}, pmid = {31739448}, issn = {1999-4915}, mesh = {Amino Acid Sequence ; Bacteria/*virology ; Bacteriolysis/*genetics ; Bacteriophages/*physiology ; Escherichia coli/virology ; Models, Molecular ; Protein Conformation ; Proteomics/*methods ; Structure-Activity Relationship ; Viral Proteins/chemistry/*genetics/*metabolism ; }, abstract = {The rapid emergence of antibiotic resistance among many pathogenic bacteria has created a profound need to discover new alternatives to antibiotics. Bacteriophages, the viruses of microbes, express special proteins to overtake the metabolism of the bacterial host they infect, the best known of which are involved in bacterial lysis. However, the functions of majority of bacteriophage encoded gene products are not known, i.e., they represent the hypothetical proteins of unknown function (HPUFs). In the current study we present a phage genomics-based screening approach to identify phage HPUFs with antibacterial activity with a long-term goal to use them as leads to find unknown targets to develop novel antibacterial compounds. The screening assay is based on the inhibition of bacterial growth when a toxic gene is expression-cloned into a plasmid vector. It utilizes an optimized plating assay producing a significant difference in the number of transformants after ligation of the toxic and non-toxic genes into a cloning vector. The screening assay was first tested and optimized using several known toxic and non-toxic genes. Then, it was applied to screen 94 HPUFs of bacteriophage φR1-RT, and identified four HPUFs that were toxic to Escherichia coli. This optimized assay is in principle useful in the search for bactericidal proteins of any phage, and also opens new possibilities to understanding the strategies bacteriophages use to overtake bacterial hosts.}, }
@article {pmid31739446, year = {2019}, author = {Loverdos, K and Bellos, G and Kokolatou, L and Vasileiadis, I and Giamarellos, E and Pecchiari, M and Koulouris, N and Koutsoukou, A and Rovina, N}, title = {Lung Microbiome in Asthma: Current Perspectives.}, journal = {Journal of clinical medicine}, volume = {8}, number = {11}, pages = {}, pmid = {31739446}, issn = {2077-0383}, abstract = {A growing body of evidence implicates the human microbiome as a potentially influential player actively engaged in shaping the pathogenetic processes underlying the endotypes and phenotypes of chronic respiratory diseases, particularly of the airways. In this article, we specifically review current evidence on the characteristics of lung microbiome, and specifically the bacteriome, the modes of interaction between lung microbiota and host immune system, the role of the "lung-gut axis", and the functional effects thereof on asthma pathogenesis. We also attempt to explore the possibilities of therapeutic manipulation of the microbiome, aiming at the establishment of asthma prevention strategies and the optimization of asthma treatment.}, }
@article {pmid31737164, year = {2019}, author = {Kang, W and Jia, Z and Tang, D and Zhang, Z and Gao, H and He, K and Feng, Q}, title = {Fusobacterium nucleatum Facilitates Apoptosis, ROS Generation, and Inflammatory Cytokine Production by Activating AKT/MAPK and NF-κB Signaling Pathways in Human Gingival Fibroblasts.}, journal = {Oxidative medicine and cellular longevity}, volume = {2019}, number = {}, pages = {1681972}, pmid = {31737164}, issn = {1942-0994}, mesh = {Adult ; Apoptosis ; Cells, Cultured ; Cytokines/metabolism ; Extracellular Signal-Regulated MAP Kinases/metabolism ; Female ; Fibroblasts/*metabolism/pathology ; Fusobacterium Infections/*metabolism ; Fusobacterium nucleatum/*physiology ; Gingiva/*pathology ; Humans ; Inflammation Mediators/metabolism ; Male ; NF-kappa B/metabolism ; Oncogene Protein v-akt/metabolism ; Periodontitis/*metabolism ; Reactive Oxygen Species/metabolism ; Signal Transduction ; }, abstract = {Fusobacterium nucleatum (F. nucleatum) plays key roles in the initiation and progression of periodontitis. However, the pathogenic effect of F. nucleatum on human oral tissues and cells has not been fully evaluated. In this study, we aimed to analyze the pathogenic effects of F. nucleatum on human gingival fibroblasts (GFs) and clarify the potential mechanisms. RNA-sequencing analysis confirmed that F. nucleatum significantly altered the gene expression of GF as the stimulation time increased. Cell counting and EdU-labeling assays indicated that F. nucleatum inhibited GF proliferation and promoted cell apoptosis in a time- and dose-dependent manner. In addition, cell apoptosis, intracellular reactive oxygen species (ROS) generation, and proinflammatory cytokine production were dramatically elevated after F. nucleatum stimulation. Furthermore, we found that the AKT/MAPK and NF-κB signaling pathways were significantly activated by F. nucleatum infection and that a large number of genes related to cellular proliferation, apoptosis, ROS, and inflammatory cytokine production downstream of AKT/MAPK and NF-κB signaling pathways were significantly altered in F. nucleatum-stimulated GFs. These findings suggest that F. nucleatum inhibits GF proliferation and promotes cell apoptosis, ROS generation, and inflammatory cytokine production partly by activating the AKT/MAPK and NF-κB signaling pathways. Our study opens a new window for understanding the pathogenic effects of periodontal pathogens on the host oral system.}, }
@article {pmid31736896, year = {2019}, author = {Bui, TPN and Schols, HA and Jonathan, M and Stams, AJM and de Vos, WM and Plugge, CM}, title = {Mutual Metabolic Interactions in Co-cultures of the Intestinal Anaerostipes rhamnosivorans With an Acetogen, Methanogen, or Pectin-Degrader Affecting Butyrate Production.}, journal = {Frontiers in microbiology}, volume = {10}, number = {}, pages = {2449}, pmid = {31736896}, issn = {1664-302X}, abstract = {The human intestinal tract harbors diverse and complex microbial communities that have a vast metabolic capacity including the breakdown of complex carbohydrates into short chain fatty acids, acetate, propionate, and butyrate. As butyrate is beneficial for gut health there is much attention on butyrogenic bacteria and their role in the colonic anaerobic food chain. However, our understanding how production of butyrate by gut microorganisms is controlled by interactions between different species and environmental nutrient availability is very limited. To address this, we set up experimental in vitro co-culture systems to study the metabolic interactions of Anaerostipes rhamnosivorans, a butyrate producer with each of its partners; Blautia hydrogenotrophica, an acetogen; Methanobrevibacter smithii, a methanogen and Bacteroides thetaiotaomicron, a versatile degrader of plant cell wall pectins; through corresponding specific cross-feeding. In all co-cultures, A. rhamnosivorans was able to benefit from its partner for enhanced butyrate formation compared to monocultures. Interspecies transfer of hydrogen or formate from A. rhamnosivorans to the acetogen B. hydrogenotrophica and in turn of acetate from the acetogen to the butyrogen were essential for butyrate formation. A. rhamnosivorans grown on glucose supported growth of M. smithii via interspecies formate/hydrogen transfer enhancing butyrate formation. In the co-culture with pectin, lactate was released by B. thetaiotaomicron which was concomitantly used by A. rhamnosivorans for the production of butyrate. Our findings indicate enhanced butyrate formation through microbe-microbe interactions between A. rhamnosivorans and an acetogen, a methanogen or a pectin-degrader. Such microbial interactions enhancing butyrate formation may be beneficial for colonic health.}, }
@article {pmid31728100, year = {2019}, author = {Migacz-Gruszka, K and Branicki, W and Obtulowicz, A and Pirowska, M and Gruszka, K and Wojas-Pelc, A}, title = {What's New in the Pathophysiology of Alopecia Areata? The Possible Contribution of Skin and Gut Microbiome in the Pathogenesis of Alopecia - Big Opportunities, Big Challenges, and Novel Perspectives.}, journal = {International journal of trichology}, volume = {11}, number = {5}, pages = {185-188}, pmid = {31728100}, issn = {0974-7753}, abstract = {The term "microbiome" defines the collective genome of all commensal, symbiotic, and pathogenic microbes living in the human body. The composition of microbiota in the gut and skin is influenced by many factors such as the stage of life, nutrition, lifestyle, and gender. In the past few years, several scientific papers have demonstrated an implication of microbiota in many immune-mediated diseases, for example, diabetes, ulcerative colitis, and multiple sclerosis. The alterations in the proportion of gut microbiota have emerged as potential immunomodulators with the capacity to induce physiologic as well as pathologic immune responses against the human body, causing inflammation and destruction of tissues or organs. The microbiota influences the differentiation of adaptive immune cells not only in the gut but also in the skin. Alopecia areata (AA) is a dermatologic disorder which causes hair loss in most cases resistant to treatment. There are some clinical and experimental evidences indicating that AA is the demonstration of autoimmune attack against hair follicles. The factors that may implicate such an autoimmunity in AA still remain unknown. Despite more and more evidences demonstrate that human microbiome plays a key role in human health and diseases, to the best of our knowledge, no study has been conducted to analyze an implication of microbiome in the pathogenesis of AA. Undoubtedly, there is a need to performing a study which might explain the involvement of gut and skin microbiota in the unclear pathogenesis of AA and lead to alternative treatment options for numerous patients suffering from current treatment limitations.}, }
@article {pmid31726030, year = {2019}, author = {Fehlner-Peach, H and Magnabosco, C and Raghavan, V and Scher, JU and Tett, A and Cox, LM and Gottsegen, C and Watters, A and Wiltshire-Gordon, JD and Segata, N and Bonneau, R and Littman, DR}, title = {Distinct Polysaccharide Utilization Profiles of Human Intestinal Prevotella copri Isolates.}, journal = {Cell host &amp; microbe}, volume = {26}, number = {5}, pages = {680-690.e5}, pmid = {31726030}, issn = {1934-6069}, support = {TL1 TR001447/TR/NCATS NIH HHS/United States ; P30 CA016087/CA/NCI NIH HHS/United States ; /ERC_/European Research Council/International ; UL1 RR029893/RR/NCRR NIH HHS/United States ; /HHMI_/Howard Hughes Medical Institute/United States ; R01 AR074500/AR/NIAMS NIH HHS/United States ; UL1 TR001445/TR/NCATS NIH HHS/United States ; T32 CA009161/CA/NCI NIH HHS/United States ; }, mesh = {Diet ; Gastrointestinal Microbiome/*physiology ; Genetic Variation ; Genome, Bacterial/genetics ; Humans ; Intestines/microbiology ; Plants/microbiology ; Polysaccharides/*metabolism ; Prevotella/classification/*isolation &amp; purification/*metabolism ; }, abstract = {Gut-dwelling Prevotella copri (P. copri), the most prevalent Prevotella species in the human gut, have been associated with diet and disease. However, our understanding of their diversity and function remains rudimentary because studies have been limited to 16S and metagenomic surveys and experiments using a single type strain. Here, we describe the genomic diversity of 83 P. copri isolates from 11 human donors. We demonstrate that genomically distinct isolates, which can be categorized into different P. copri complex clades, utilize defined sets of polysaccharides. These differences are exemplified by variations in susC genes involved in polysaccharide transport as well as polysaccharide utilization loci (PULs) that were predicted in part from genomic and metagenomic data. Functional validation of these PULs showed that P. copri isolates utilize distinct sets of polysaccharides from dietary plant, but not animal, sources. These findings reveal both genomic and functional differences in polysaccharide utilization across human intestinal P. copri strains.}, }
@article {pmid31721508, year = {2019}, author = {Liu, YK and Xu, X and Zhou, XD}, title = {[Potential application of human microbiomes in the diagnosis and treatment of type 2 diabetes mellitus].}, journal = {Hua xi kou qiang yi xue za zhi = Huaxi kouqiang yixue zazhi = West China journal of stomatology}, volume = {37}, number = {5}, pages = {556-562}, pmid = {31721508}, issn = {2618-0456}, mesh = {*Diabetes Mellitus, Type 2 ; *Gastrointestinal Microbiome ; Humans ; *Microbiota ; }, abstract = {Human microbiome refers to the total microorganism genetic information of human body surface and internal, which is closely related to human health and disease. Oral and gut microbiomes are the most diverse microbial communities, which can interact and play a role in the development of the disease, and can reflect the health and disease state in real time. Type 2 diabetes mellitus is a metabolic disorder caused by both genetic and environmental factors. Recent research has shown a link between microbes and diabetes. This article reviewed the latest research on the changes of oral and gut microbiomes in type 2 diabetes mellitus patients, which expects to provide a reference for exploring the development of the disease model for prediction, diagnosis and prognosis of type 2 diabetes mellitus based on human microbiome characteristics.}, }
@article {pmid31719221, year = {2019}, author = {Chaudhari, D and Dhotre, D and Agarwal, D and Gondhali, A and Nagarkar, A and Lad, V and Patil, U and Juvekar, S and Sinkar, V and Shouche, Y}, title = {Understanding the association between the human gut, oral and skin microbiome and the Ayurvedic concept of prakriti.}, journal = {Journal of biosciences}, volume = {44}, number = {5}, pages = {}, pmid = {31719221}, issn = {0973-7138}, mesh = {Female ; Humans ; Intestines/*microbiology ; Male ; *Medicine, Ayurvedic ; *Microbiota ; Mouth/*microbiology ; Skin/*microbiology ; }, abstract = {Ayurveda is one of the ancient systems of medicine which is widely practised as a personalized scientific approach towards the general wellness. Ayurvedic prakriti is broadly defined as the phenotypes which are determined on the basis of physical, psychological and physiological traits irrespective of their social, ethnic, dietary and geographical stature. Prakriti is the constitution of a person, which comprises vata, pitta, and kapha and is a key determinant of how one individual is different from the other. Human microbiome is considered the 'latest discovered' human organ and microbiome research reiterates the fundamental principles of Ayurveda for creating a healthy gut environment by maintaining the individual-specific microbiome. Hence, it is important to understand the association of human microbiome with the Ayurvedic prakriti of an individual. Here, we provide a comprehensive analysis of human microbiome from the gut, oral and skin samples of healthy individuals (n=18) by 16S rRNA gene-based metagenomics using standard QIIME pipeline. In the three different prakriti samples differential abundance of Bacteroides, Desulfovibrio, Parabacteroides, Slackia, and Succinivibrio was observed in the gut microbiome. Analysis also revealed prakriti-specific presence of Mogibacterium, Propionibacterium, Pyramidobacter, Rhodococcus in the kapha prakriti individuals Planomicrobium, Hyphomicrobium, Novosphingobium in the pitta prakriti individuals and Carnobacterium, Robiginitalea, Cetobacterium, Psychrobacter in the vata prakriti individuals. Similarly, the oral and skin microbiome also revealed presence of prakriti-specific differential abundance of diverse bacterial genera. Prakriti-specific presence of bacterial taxa was recorded and only 42% microbiome in the oral samples and 52% microbiome in the skin samples were shared. Bacteria known for preventing gut inflammation by digesting the resistant starch were abundant in the pitta prakriti individuals, who are more prone to develop gut-inflammation-related disorders. In summary, human gut, oral and skin microbiome showed presence or high abundance of few bacterial taxa across three prakriti types, suggesting their specific physiological importance.}, }
@article {pmid31719220, year = {2019}, author = {Holmes, S}, title = {Successful strategies for human microbiome data generation, storage and analyses.}, journal = {Journal of biosciences}, volume = {44}, number = {5}, pages = {}, pmid = {31719220}, issn = {0973-7138}, mesh = {Humans ; *Microbiota ; Multivariate Analysis ; Probability ; Reproducibility of Results ; }, abstract = {Current interest in the potential for clinical use of new tools for improving human health are now focused on techniques for the study of the human microbiome and its interaction with environmental and clinical covariates. This review outlines the use of statistical strategies that have been developed in past studies and can inform successful design and analyses of controlled perturbation experiments performed in the human microbiome. We carefully outline what the data are, their imperfections and how we need to transform, decontaminate and denoise them. We show how to identify the important unknown parameters and how to can leverage variability we see to produce efficient models for prediction and uncertainty quantification. We encourage a reproducible strategy that builds on best practice principles that can be adapted for effective experimental design and reproducible workflows. Nonparametric, data-driven denoising strategies already provide the best strain identification and decontamination methods. Data driven models can be combined with uncertainty quantification to provide reproducible aids to decision making in the clinical context, as long as careful, separate, registered confirmatory testing are undertaken. Here we provide guidelines for effective longitudinal studies and their analyses. Lessons learned along the way are that visualizations at every step can pinpoint problems and outliers, normalization and filtering improve power in downstream testing. We recommend collecting and binding the metadata and covariates to sample descriptors and recording complete computer scripts into an R markdown supplement that can reduce opportunities for human error and enable collaborators and readers to replicate all the steps of the study. Finally, we note that optimizing the bioinformatic and statistical workflow involves adopting a wait-and-see approach that is particularly effective in cases where the features such as 'mass spectrometry peaks' and metagenomic tables can only be partially annotated.}, }
@article {pmid31717688, year = {2019}, author = {Wojciuk, B and Salabura, A and Grygorcewicz, B and Kędzierska, K and Ciechanowski, K and Dołęgowska, B}, title = {Urobiome: In Sickness and in Health.}, journal = {Microorganisms}, volume = {7}, number = {11}, pages = {}, pmid = {31717688}, issn = {2076-2607}, abstract = {The human microbiome has been proven to contribute to the human condition, both in health and in disease. The metagenomic approach based on next-generation sequencing has challenged the dogma of urine sterility. The human urobiome consists of bacteria and eukaryotic viruses as well as bacteriophages, which potentially represent the key factor. There have been several significant findings with respect to the urobiome in the context of urological disorders. Still, the research on the urobiome in chronic kidney disease and kidney transplantation remains underrepresented, as does research on the role of the virome in the urinary microbiota. In this review, we present recent findings on the urobiome with a particular emphasis on chronic kidney disease and post-kidney transplantation status. Challenges and opportunities arising from the research on the human urobiome will also be discussed.}, }
@article {pmid31713170, year = {2019}, author = {Astudillo-de la Vega, H and Alonso-Luna, O and Ali-Pérez, J and López-Camarillo, C and Ruiz-Garcia, E}, title = {Oncobiome at the Forefront of a Novel Molecular Mechanism to Understand the Microbiome and Cancer.}, journal = {Advances in experimental medicine and biology}, volume = {1168}, number = {}, pages = {147-156}, doi = {10.1007/978-3-030-24100-1_10}, pmid = {31713170}, issn = {0065-2598}, mesh = {Bacteria/genetics ; Dysbiosis ; High-Throughput Nucleotide Sequencing ; Humans ; Metagenomics ; *Microbiota/genetics/physiology ; *Neoplasms/microbiology ; }, abstract = {The microbiome comprises all the genetic material within a microbiota, that represents tenfold higher than that of our cells. The microbiota it includes a wide variety of microorganisms such as bacteria, viruses, protozoans, fungi, and archaea, and this ecosystem is personalized in any body space of every individual. Balanced microbial communities can positively contribute to training the immune system and maintaining immune homeostasis. Dysbiosis is a change in the normal microbiome composition that can initiate chronic inflammation, epithelial barrier breaches, and overgrowth of harmful bacteria. The next-generation sequencing methods have revolutionized the study of the microbiome. Bioinformatic tools to manage large volumes of new information, it became possible to assess species diversity and measure dynamic fluctuations in microbial communities. The burden of infections that are associated to human cancer is increasing but is underappreciated by the cancer research community. The rich content in microbes of normal and tumoral tissue reflect could be defining diverse physiological or pathological states. Genomic research has emerged a new focus on the interplay between the human microbiome and carcinogenesis and has been termed the 'oncobiome'. The interactions among the microbiota in all epithelium, induce changes in the host immune interactions and can be a cause of cancer. Microbes have been shown to have systemic effects on the host that influence the efficacy of anticancer drugs. Metagenomics allows to investigate the composition of microbial community. Metatranscriptome analysis applies RNA sequencing to microbial samples to determine which species are present. Cancer can be caused by changes in the microbiome. The roles of individual microbial species in cancer progression have been identified long ago for various tissue types. The identification of microbiomes of drug resistance in the treatment of cancer patients has been the subject of numerous microbiome studies. The complexity of cancer genetic alterations becomes irrelevant in certain cancers to explain the origin, the cause or the oncogenic maintenance by the oncogene addiction theory.}, }
@article {pmid31708974, year = {2019}, author = {Bianchi, M and Alisi, A and Fabrizi, M and Vallone, C and Ravà, L and Giannico, R and Vernocchi, P and Signore, F and Manco, M}, title = {Maternal Intake of n-3 Polyunsaturated Fatty Acids During Pregnancy Is Associated With Differential Methylation Profiles in Cord Blood White Cells.}, journal = {Frontiers in genetics}, volume = {10}, number = {}, pages = {1050}, pmid = {31708974}, issn = {1664-8021}, abstract = {A healthy diet during pregnancy is pivotal for the offspring health at birth and later in life. N-3 polyunsaturated fatty acids (n-3 PUFAs) are not endogenously produced in humans and are exclusively derived from the diet. They are pivotal for the fetus growth and neuronal development and seem beneficial in reducing the risk of cardiometabolic diseases and preventing later allergic disorders in the offspring by modulating the inflammatory immune response. In the present study, we investigated the association between maternal intakes of n-3PUFAs, profiled on maternal erythrocyte membranes at pregnancy term, and offspring DNA methylation on cord blood mononuclear cells in a sample of 118 mother-newborn pairs randomly drawn from the "Feeding fetus' low-grade inflammation and insulin-resistance" study cohort. N-3 PUFA content on erythrocyte membranes is a validated biomarker to measure objectively medium term intake of n-3 PUFAs. Based on distribution of n-3 PUFA in the whole cohort of mothers, we identified mothers with low (n-3 PUFA concentration <25th percentile), medium (n-3 PUFAs between 25th and 75th percentiles), and high n-3 PUFA content (>75th percentile). The HumanMethylation450 BeadChip (Illumina) was used for the epigenome-wide association study using the Infinium Methylation Assay. The overall DNA methylation level was not different between the three groups while there was significant difference in methylation levels at certain sites. Indeed, 8,503 sites had significantly different methylations between low and high n-3 PUFA groups, 12,716 between low and medium n-3 PUFA groups, and 18,148 between high and medium n-3 PUFA groups. We found differentially methylated genes that belong prevalently to pathways of signal transduction, metabolism, downstream signaling of G protein-coupled receptors, and gene expression. Within these pathways, we identified four differentially methylated genes, namely, MSTN, IFNA13, ATP8B3, and GABBR2, that are involved in the onset of insulin resistance and adiposity, innate immune response, phospholipid translocation across cell membranes, and mechanisms of addiction to high fat diet, alcohol, and sweet taste. In conclusion, findings of this preliminary investigation suggest that maternal intake of n-3 PUFAs during pregnancy has potential to influence the offspring DNA methylation. Validation of results in a larger cohort and investigation of biological significance and impact on the phenotype are warranted.}, }
@article {pmid31707219, year = {2019}, author = {Stubbendieck, RM and Li, H and Currie, CR}, title = {Convergent evolution of signal-structure interfaces for maintaining symbioses.}, journal = {Current opinion in microbiology}, volume = {50}, number = {}, pages = {71-78}, pmid = {31707219}, issn = {1879-0364}, support = {T15 LM007359/LM/NLM NIH HHS/United States ; U19 AI109673/AI/NIAID NIH HHS/United States ; U19 TW009872/TW/FIC NIH HHS/United States ; }, mesh = {Animals ; Ants/microbiology ; Decapodiformes/microbiology ; *Evolution, Molecular ; Fabaceae/microbiology ; *Host Microbial Interactions ; Humans ; *Microbiota ; *Symbiosis ; }, abstract = {Symbiotic microbes are essential to the ecological success and evolutionary diversification of multicellular organisms. The establishment and stability of bipartite symbioses are shaped by mechanisms ensuring partner fidelity between host and symbiont. In this minireview, we demonstrate how the interface of chemical signals and host structures influences fidelity between legume root nodules and rhizobia, Hawaiian bobtail squid light organs and Allivibrio fischeri, and fungus-growing ant crypts and Pseudonocardia. Subsequently, we illustrate the morphological diversity and widespread phylogenetic distribution of specialized structures used by hosts to house microbial symbionts, indicating the importance of signal-structure interfaces across the history of multicellular life. These observations, and the insights garnered from well-studied bipartite associations, demonstrate the need to concentrate on the signal-structure interface in complex and multipartite systems, including the human microbiome.}, }
@article {pmid31699101, year = {2019}, author = {Kumpitsch, C and Koskinen, K and Schöpf, V and Moissl-Eichinger, C}, title = {The microbiome of the upper respiratory tract in health and disease.}, journal = {BMC biology}, volume = {17}, number = {1}, pages = {87}, pmid = {31699101}, issn = {1741-7007}, mesh = {Humans ; *Microbiota ; Nose/*microbiology ; Respiratory Tract Infections/*microbiology ; Trachea/*microbiology ; }, abstract = {The human upper respiratory tract (URT) offers a variety of niches for microbial colonization. Local microbial communities are shaped by the different characteristics of the specific location within the URT, but also by the interaction with both external and intrinsic factors, such as ageing, diseases, immune responses, olfactory function, and lifestyle habits such as smoking. We summarize here the current knowledge about the URT microbiome in health and disease, discuss methodological issues, and consider the potential of the nasal microbiome to be used for medical diagnostics and as a target for therapy.}, }
@article {pmid31690595, year = {2019}, author = {Maixner, F}, title = {Molecular Reconstruction of the Diet in Human Stool Samples.}, journal = {mSystems}, volume = {4}, number = {6}, pages = {}, pmid = {31690595}, issn = {2379-5077}, abstract = {Understanding dietary effects on the gut microbial composition is one of the key questions in human microbiome research. It is highly important to have reliable dietary data on the stool samples to unambiguously link the microbiome composition to food intake. Often, however, self-reported diet surveys have low accuracy and can be misleading. Thereby, additional molecular biology-based methods could help to revise the diet composition. The article by Reese et al. [A. T. Reese, T. R. Kartzinel, B. L. Petrone, P. J. Turnbaugh, et al., mSystems 4(5):e00458-19, 2019, https://doi.org/10.1128/mSystems.00458-19] in a recent issue of mSystems describes a DNA metabarcoding strategy targeting chloroplast DNA markers in stool samples from 11 human subjects consuming both controlled and freely selected diets. The aim of this study was to evaluate the efficiency of this molecular method in detecting plant remains in the sample compared to the written dietary records. This study displays an important first step in implementing molecular dietary reconstructions in stool microbiome studies which will finally help to increase the accuracy of dietary metadata.}, }
@article {pmid31685450, year = {2019}, author = {Agorastos, A and Bozikas, VP}, title = {Gut microbiome and adaptive immunity in schizophrenia.}, journal = {Psychiatrike = Psychiatriki}, volume = {30}, number = {3}, pages = {189-192}, doi = {10.22365/jpsych.2019.303.189}, pmid = {31685450}, issn = {1105-2333}, mesh = {*Adaptive Immunity ; *Gastrointestinal Microbiome ; Humans ; Schizophrenia/*immunology/*microbiology ; }, abstract = {Over the past few years, immunopathogenesis has emerged as one of the most compelling aetiopathological models of schizophrenia (SCZ), suggesting a chronic, immune-based, low-grade inflammatory background of this devastating disorder.1,2 Mounting evidence points towards a prominent role of the adaptive immune system in SCZ, suggesting alterations in defense mechanisms, such as altered T-cell function and a shift towards B-cell immunity.3 Immune cells have the ability to infiltrate the brain and mediate a neuroimmune cross-talk through activation of microglia, production of proinflammatory cytokines and reactive oxygen species, leading to neuroinflammation, as mediator of neuroprogressive and neurodegenerative changes in SCZ.4 Antipsychotic drugs, commonly used to treat SCZ, are also known to affect the adaptive immune system, interfering with the differentiation and function of immune cells, towards their normalization in response to treatment. Adaptive immunity is principally founded on T-cell and B-cell populations, but also includes the host microbiome. The gastrointestinal microbiota is a complex ecosystem with a great organism diversity and refined genomic structure that resides in the intestinal tract and has a central position in human health and disease.5 Neuroimmune dysregulation, relying of the highly sensitive and fine-tuned equilibrium between microbiome and adaptive immunity, can tip the scales towards neuroinflammation and disruption of higher-order brain networks.4,6,7 During the last decade, the human microbiome and the microbiota-gut-brain (MGB)-axis have become a novel epicentre in mental health research as a potentially vital new determinant in the field of neuroimmunoregulation, brain development, emotions, cognition and behaviour.7 The MGB-axis represents a bidirectional, key communication pathway between the immune system and the brain, thus partly also mediating the regulation of cognitive and emotional processing. An imbalanced human microbiome might greatly influence proper neuroimmune reactions and neurodevelopment with long-lasting effects and could thus play a pivotal role in the susceptibility and aetiology of psychiatric illness. Recent research offers first evidence that patients with SCZ show marked disturbances of gut bacterial taxa composition with a decreased microbiome diversity index, party associated with specific SCZ phenotype, symptom severity and treatment response.8,9 As the elegant education of the adaptive immune compartment depends on the colonization niche, antigen type and metabolic property of different gut microbes, T-cell differentiation as well as a continuous diversification of B-cell repertoire is expressed through microbiome-related, antigen-specific receptors that define a unique clonotype.10 However, there is only sparse evidence on the precise role of the microbiome on the programming of T- and B-cells in the underlying neurobiological pathways of SCZ and even less findings on the association of molecular T- and B-cell receptor repertoire signature and microbiome clonal landscape with specific phenotypical features of the disease.11 The latest conceptual advances in immunology urge an integrative re-evaluation of previous immunological findings in SCZ through modern approaches. High-throughput, next-generation sequencing (NGS) represents a powerful singlecell transcriptomic tool to profile the whole clonal landscape of T and B cells and human microbiome. NGS thus offers a unique opportunity for in-depth characterization of cellular and molecular signatures of adaptive immune receptor repertoires and microbiome taxonomy in SCZ and investigation of their intersection as a relevant pathway of disease progression and phenotype differentiation. SCZ patients are likely to show a diverging host-microbiome immune homeostasis with disease-specific clonotypes of adaptive immune receptor repertoires associated with altered microbiome taxonomy and molecular signature differences, which, in turn, may be related to distinct symptomatic phenotypes and neurocognitive patterns. Such sophisticated immuno-bioinformatic analyses may transform our understanding of SCZ by identification of novel neuroimmune pathways, offering us clinically accessible symptomatic and diagnostic biomarkers important for personalized medicine implications.12 An increased understanding and better characterization of immuno-phenotypes in SCZ will better guide the development of novel immune-based treatments in this severe disease and pave the way for possible prevention options through implementation of antibody engineering, vaccine design, and cellular immunotherapy.}, }
@article {pmid31683170, year = {2019}, author = {Orlandi, E and Iacovelli, NA and Tombolini, V and Rancati, T and Polimeni, A and De Cecco, L and Valdagni, R and De Felice, F}, title = {Potential role of microbiome in oncogenesis, outcome prediction and therapeutic targeting for head and neck cancer.}, journal = {Oral oncology}, volume = {99}, number = {}, pages = {104453}, doi = {10.1016/j.oraloncology.2019.104453}, pmid = {31683170}, issn = {1879-0593}, mesh = {Carcinogenesis/*genetics ; Head and Neck Neoplasms/*genetics/*therapy ; Humans ; Immunotherapy/*methods ; Microbiota/*genetics ; Prognosis ; Treatment Outcome ; }, abstract = {In the last decade, human microbiome research is rapidly growing involving several fields of clinical medicine and population health. Although the microbiome seems to be linked to all sorts of diseases, cancer has the biggest potential to be investigated. Following the publication of the National Institute of Health - Human Microbiome Project (NIH-HMP), the link between Head and Neck Cancer (HNC) and microbiome seems to be a fast-moving field in research area. However, robust evidence-based literature is still quite scarce. Nevertheless the relationship between oral microbiome and HNC could have important consequences for prevention and early detection of this type of tumors. The aims of the present review are: (i) to discuss current pre-clinical evidence of a role of oral microbiome in HNC; (ii) to report recent developments in understanding the human microbiome's relationship with HNC oncogenesis; (iii) to explore the issue of treatment response and treatment toxicity; (iv) to describe the role of microbiota as potentially modifiable factor suitable for targeting by therapeutics. Further studies are needed to better establish the causal relationship between oral microbiome and HNC oncogenesis. Future trials should continue to explore oral microbiome in order to build the scientific and clinical rationale of HNC preventative and ameliorate treatment outcome.}, }
@article {pmid31683111, year = {2019}, author = {Porras, AM and Brito, IL}, title = {The internationalization of human microbiome research.}, journal = {Current opinion in microbiology}, volume = {50}, number = {}, pages = {50-55}, pmid = {31683111}, issn = {1879-0364}, support = {R01 DK093595/DK/NIDDK NIH HHS/United States ; }, mesh = {Disease/etiology ; *Gastrointestinal Microbiome ; Genetic Variation ; *Global Health ; Host Microbial Interactions ; Humans ; *Research ; }, abstract = {The human microbiome has now been linked with myriad diseases, yet most of this research has been conducted on American and European populations that make up only 1/6th of the world's population. With growing recognition that human microbiomes differ tremendously across global populations, it is especially important to understand how these compositional differences impact health outcomes. Recent advances in infectious disease and malnutrition research have demonstrated the potential for microbiome-based strategies to address the biggest challenges in global health. This review highlights major advances toward understanding microbiome diversity across the world and its contributions to disease, and outlines key questions, challenges, and opportunities to broaden the scope of and promote inclusivity within microbiome research.}, }
@article {pmid31681437, year = {2019}, author = {Shah, N and Meisel, JS and Pop, M}, title = {Embracing Ambiguity in the Taxonomic Classification of Microbiome Sequencing Data.}, journal = {Frontiers in genetics}, volume = {10}, number = {}, pages = {1022}, pmid = {31681437}, issn = {1664-8021}, abstract = {The advent of high throughput sequencing has enabled in-depth characterization of human and environmental microbiomes. Determining the taxonomic origin of microbial sequences is one of the first, and frequently only, analysis performed on microbiome samples. Substantial research has focused on the development of methods for taxonomic annotation, often making trade-offs in computational efficiency and classification accuracy. A side-effect of these efforts has been a reexamination of the bacterial taxonomy itself. Taxonomies developed prior to the genomic revolution captured complex relationships between organisms that went beyond uniform taxonomic levels such as species, genus, and family. Driven in part by the need to simplify computational workflows, the bacterial taxonomies used most commonly today have been regularized to fit within a standard seven taxonomic levels. Consequently, modern analyses of microbial communities are relatively coarse-grained. Few methods make classifications below the genus level, impacting our ability to capture biologically relevant signals. Here, we present ATLAS, a novel strategy for taxonomic annotation that uses significant outliers within database search results to group sequences in the database into partitions. These partitions capture the extent of taxonomic ambiguity within the classification of a sample. The ATLAS pipeline can be found on GitHub [https://github.com/shahnidhi/outlier_in_BLAST_hits]. We demonstrate that ATLAS provides similar annotations to phylogenetic placement methods, but with higher computational efficiency. When applied to human microbiome data, ATLAS is able to identify previously characterized taxonomic groupings, such as those in the class Clostridia and the genus Bacillus. Furthermore, the majority of partitions identified by ATLAS are at the subgenus level, replacing higher-level annotations with specific groups of species. These more precise partitions improve our detection power in determining differential abundance in microbiome association studies.}, }
@article {pmid31674689, year = {2020}, author = {Huck, O and Mulhall, H and Rubin, G and Kizelnik, Z and Iyer, R and Perpich, JD and Haque, N and Cani, PD and de Vos, WM and Amar, S}, title = {Akkermansia muciniphila reduces Porphyromonas gingivalis-induced inflammation and periodontal bone destruction.}, journal = {Journal of clinical periodontology}, volume = {47}, number = {2}, pages = {202-212}, doi = {10.1111/jcpe.13214}, pmid = {31674689}, issn = {1600-051X}, support = {R01 HL076801/HL/NHLBI NIH HHS/United States ; R01 DE014079/DE/NIDCR NIH HHS/United States ; }, mesh = {Akkermansia ; Alveolar Bone Loss/*prevention &amp; control ; Animals ; Disease Models, Animal ; Gingiva ; Inflammation ; Mice ; *Periodontitis ; Porphyromonas gingivalis ; Verrucomicrobia ; }, abstract = {AIM: Akkermansia muciniphila is a beneficial gut commensal, whose anti-inflammatory properties have recently been demonstrated. This study aimed to evaluate the effect of A. muciniphila on Porphyromonas gingivalis elicited inflammation.<br><br>MATERIAL AND METHODS: In lean and obese mice, A. muciniphila was administered in P. gingivalis-induced calvarial abscess and in experimental periodontitis model (EIP). Bone destruction and inflammation were evaluated by histomorphometric analysis. In vitro, A. muciniphila was co-cultured with P. gingivalis, growth and virulence factor expression was evaluated. Bone marrow macrophages (BMM&#x3d5;) and gingival epithelial cells (TIGK) were exposed to both bacterial strains, and the expression of inflammatory mediators, as well as tight junction markers, was analysed.<br><br>RESULTS: In a model of calvarial infection, A. muciniphila decreased inflammatory cell infiltration and bone destruction. In EIP, treatment with A. muciniphila resulted in a decreased alveolar bone loss. In vitro, the addition of A. muciniphila to P. gingivalis-infected BMM&#x3d5; increased anti-inflammatory IL-10 and decreased IL-12. Additionally, A. muciniphila exposure increases the expression of junctional integrity markers such as integrin-&#x3b2;1, E-cadherin and ZO-1 in TIGK cells. A. muciniphila co-culture with P. gingivalis reduced gingipains mRNA expression.<br><br>DISCUSSION: This study demonstrated the protective effects of A. muciniphila administration and may open consideration to its use as an adjunctive therapeutic agent to periodontal treatment.}, }
@article {pmid31666099, year = {2019}, author = {Zhu, C and Miller, M and Lusskin, N and Mahlich, Y and Wang, Y and Zeng, Z and Bromberg, Y}, title = {Fingerprinting cities: differentiating subway microbiome functionality.}, journal = {Biology direct}, volume = {14}, number = {1}, pages = {19}, pmid = {31666099}, issn = {1745-6150}, support = {U01 GM115486/GM/NIGMS NIH HHS/United States ; U01 GM115486/NH/NIH HHS/United States ; }, mesh = {Cities ; *Metagenome ; *Microbiota ; *Railroads ; }, abstract = {BACKGROUND: Accumulating evidence suggests that the human microbiome impacts individual and public health. City subway systems are human-dense environments, where passengers often exchange microbes. The MetaSUB project participants collected samples from subway surfaces in different cities and performed metagenomic sequencing. Previous studies focused on taxonomic composition of these microbiomes and no explicit functional analysis had been done till now.<br><br>RESULTS: As a part of the 2018 CAMDA challenge, we functionally profiled the available ~&#x2009;400 subway metagenomes and built predictor for city origin. In cross-validation, our model reached 81% accuracy when only the top-ranked city assignment was considered and 95% accuracy if the second city was taken into account as well. Notably, this performance was only achievable if the similarity of distribution of cities in the training and testing sets was similar. To assure that our methods are applicable without such biased assumptions we balanced our training data to account for all represented cities equally well. After balancing, the performance of our method was slightly lower (76/94%, respectively, for one or two top ranked cities), but still consistently high. Here we attained an added benefit of independence of training set city representation. In testing, our unbalanced model thus reached (an over-estimated) performance of 90/97%, while our balanced model was at a more reliable 63/90% accuracy. While, by definition of our model, we were not able to predict the microbiome origins previously unseen, our balanced model correctly judged them to be NOT-from-training-cities over 80% of the time. Our function-based outlook on microbiomes also allowed us to note similarities between both regionally close and far-away cities. Curiously, we identified the depletion in mycobacterial functions as a signature of cities in New Zealand, while photosynthesis related functions fingerprinted New York, Porto and Tokyo.<br><br>CONCLUSIONS: We demonstrated the power of our high-speed function annotation method, mi-faser, by analysing ~&#x2009;400 shotgun metagenomes in 2&#xa0;days, with the results recapitulating functional signals of different city subway microbiomes. We also showed the importance of balanced data in avoiding over-estimated performance. Our results revealed similarities between both geographically close (Ofa and Ilorin) and distant (Boston and Porto, Lisbon and New York) city subway microbiomes. The photosynthesis related functional signatures of NYC were previously unseen in taxonomy studies, highlighting the strength of functional analysis.}, }
@article {pmid31664160, year = {2020}, author = {Daisley, BA and Pitek, AP and Chmiel, JA and Al, KF and Chernyshova, AM and Faragalla, KM and Burton, JP and Thompson, GJ and Reid, G}, title = {Novel probiotic approach to counter Paenibacillus larvae infection in honey bees.}, journal = {The ISME journal}, volume = {14}, number = {2}, pages = {476-491}, pmid = {31664160}, issn = {1751-7370}, mesh = {Animals ; Beekeeping ; Bees/*microbiology ; Dietary Supplements/microbiology ; Gram-Positive Bacterial Infections/therapy ; Lactobacillus ; Paenibacillus larvae/*pathogenicity ; Probiotics/therapeutic use ; United States ; }, abstract = {American foulbrood (AFB) is a highly virulent disease afflicting honey bees (Apis mellifera). The causative organism, Paenibacillus larvae, attacks honey bee brood and renders entire hives dysfunctional during active disease states, but more commonly resides in hives asymptomatically as inactive spores that elude even vigilant beekeepers. The mechanism of this pathogenic transition is not fully understood, and no cure exists for AFB. Here, we evaluated how hive supplementation with probiotic lactobacilli (delivered through a nutrient patty; BioPatty) affected colony resistance towards a naturally occurring AFB outbreak. Results demonstrated a significantly lower pathogen load and proteolytic activity of honey bee larvae from BioPatty-treated hives. Interestingly, a distinctive shift in the microbiota composition of adult nurse bees occurred irrespective of treatment group during the monitoring period, but only vehicle-supplemented nurse bees exhibited higher P. larvae loads. In vitro experiments utilizing laboratory-reared honey bee larvae showed Lactobacillus plantarum Lp39, Lactobacillus rhamnosus GR-1, and Lactobacillus kunkeei BR-1 (contained in the BioPatty) could reduce pathogen load, upregulate expression of key immune genes, and improve survival during P. larvae infection. These findings suggest the usage of a lactobacilli-containing hive supplement, which is practical and affordable for beekeepers, may be effective for reducing enzootic pathogen-related hive losses.}, }
@article {pmid31662819, year = {2019}, author = {Royston, KJ and Adedokun, B and Olopade, OI}, title = {Race, the microbiome and colorectal cancer.}, journal = {World journal of gastrointestinal oncology}, volume = {11}, number = {10}, pages = {773-787}, pmid = {31662819}, issn = {1948-5204}, abstract = {In the past decade, more cancer researchers have begun to understand the significance of cancer prevention, which has prompted a shift in the increasing body of scientific literature. An area of fascination and great potential is the human microbiome. Recent studies suggest that the gut microbiota has significant roles in an individual's ability to avoid cancer, with considerable focus on the gut microbiome and colorectal cancer. That in mind, racial disparities with regard to colorectal cancer treatment and prevention are generally understudied despite higher incidence and mortality rates among Non-Hispanic Blacks compared to other racial and ethnic groups in the United States. A comprehension of ethnic differences with relation to colorectal cancer, dietary habits and the microbiome is a meritorious area of investigation. This review highlights literature that identifies and bridges the gap in understanding the role of the human microbiome in racial disparities across colorectal cancer. Herein, we explore the differences in the gut microbiota, common short chain fatty acids produced in abundance by microbes, and their association with racial differences in cancer acquisition.}, }
@article {pmid31654515, year = {2020}, author = {Musso, P and Chiappini, E and Bernardini, R}, title = {Human Microbiome and Allergic Diseases in Children: Pathogenetic Role and Therapeutic Options.}, journal = {Current pediatric reviews}, volume = {16}, number = {2}, pages = {89-94}, doi = {10.2174/1573396315666191025110849}, pmid = {31654515}, issn = {1875-6336}, mesh = {Child ; Child, Preschool ; Humans ; Hypersensitivity/immunology/*microbiology/therapy ; Infant ; Microbiota/*immunology ; Prebiotics/administration &amp; dosage ; Probiotics/therapeutic use ; }, abstract = {The recent and extensive study of the microbiome has provided an enormous amount of data concerning the type and possible functions of microorganisms present in the gut, airways, genital tract, and skin. These data showed interpersonal differences in the composition of the microbiome and these differences suggest a link between the microbiome, the immune modulation, and the pathogenesis of allergic diseases. This research is particularly relevant in paediatrics, since allergic diseases are constantly increasing and there is evidence in the paediatric age that shows that the composition of the microbiome in the foetal and neonatal period plays a key role in the development of the immune system: vaginal delivery, breastfeeding, childhood spent in rural environments and/or in contact with animals result in a greater biodiversity of the microbiome with the presence of protective species that reduce the activation of Th2 lymphocytes, involved in allergic reactions. Further studies are necessary to better understand the microbiota role in the pathogenesis of atopy in order to understand if specific probiotics and prebiotics, administered orally or topically, can affect the microbiota composition and modulate immune system functions, producing a therapeutic effect in the treatment of allergic diseases. This narrative review analysed the available literature regarding the correlation between the microbiome and the development of allergic diseases and with special focus on paediatric studies. The skin, gut or lung dysbiosis can be a cofactor in the pathogenesis of allergies and the remodulation of the microbiome becomes an important therapeutic challenge.}, }
@article {pmid31650413, year = {2020}, author = {Klimko, AI and Cherdyntseva, TA and Brioukhanov, AL and Netrusov, AI}, title = {In Vitro Evaluation of Probiotic Potential of Selected Lactic Acid Bacteria Strains.}, journal = {Probiotics and antimicrobial proteins}, volume = {12}, number = {3}, pages = {1139-1148}, pmid = {31650413}, issn = {1867-1314}, mesh = {*Antibiosis ; Bacterial Adhesion ; Biofilms ; Lactobacillus/*metabolism ; *Probiotics/metabolism ; Staphylococcus aureus ; }, abstract = {Research of human microbiome demonstrates that in order to develop next generation of probiotic agents, it is necessary to choose bacterial strains featured by special properties, such as the ability of the cells to attach to intestinal walls, resistance to bile and acids, bacteriocin synthesis, antioxidative and antipathogenic activity, and survivability in intestines. Thirty-three strains of lactic acid bacteria of Lactobacillus and Lactococcus genera from the Lomonosov Moscow State University Collection of Microorganisms (CM MSU) have been tested for important probiotic properties which assist these bacteria to settle effectively in intestines: cell adhesion, ability to form biofilms, agglutination with lectin (concanavalin A), and antimicrobial activity. The results of experiments clearly demonstrate that all these properties can be classified as strain characteristics and differ even within the same species. Besides the cultures of Lactobacillus with good agglutination ability with concanavalin A (Lact. caucasicus CM MSU 155, Lact. brevis CM MSU 521), we also discovered strains with high adhesion properties (Lact. acidophilus CM MSU 146-89% affinity for hexadecane; Lact. paracasei CM MSU 527-85%; Lact. plantarum CM MSU 508-78%; Lact. caucasicus CM MSU 155-70%; and Lact. delbrueckii CM MSU 571-57%), biofilm formation ability with a hydrophobic carrier (Lact. plantarum CM MSU 588-OD590 of crystal violet extracts = 1.336; Lact. brevis CM MSU 521-OD590 = 1.207; and Lact. brevis CM MSU 535-OD590 = 1.151), and with high antimicrobial activity specially to Staphylococcus aureus. Lact. brevis CM MSU 521 possesses the best property combination, which makes it potentially applicable as a very good lactic acid probiotic strain.}, }
@article {pmid31649646, year = {2019}, author = {Engevik, MA and Morra, CN and Röth, D and Engevik, K and Spinler, JK and Devaraj, S and Crawford, SE and Estes, MK and Kalkum, M and Versalovic, J}, title = {Microbial Metabolic Capacity for Intestinal Folate Production and Modulation of Host Folate Receptors.}, journal = {Frontiers in microbiology}, volume = {10}, number = {}, pages = {2305}, pmid = {31649646}, issn = {1664-302X}, support = {P30 CA033572/CA/NCI NIH HHS/United States ; P30 DK056338/DK/NIDDK NIH HHS/United States ; U01 CA170930/CA/NCI NIH HHS/United States ; }, abstract = {Microbial metabolites, including B complex vitamins contribute to diverse aspects of human health. Folate, or vitamin B9, refers to a broad category of biomolecules that include pterin, para-aminobenzoic acid (pABA), and glutamate subunits. Folates are required for DNA synthesis and epigenetic regulation. In addition to dietary nutrients, the gut microbiota has been recognized as a source of B complex vitamins, including folate. This study evaluated the predicted folate synthesis capabilities in the genomes of human commensal microbes identified in the Human Microbiome Project and folate production by representative strains of six human intestinal bacterial phyla. Bacterial folate synthesis genes were ubiquitous across 512 gastrointestinal reference genomes with 13% of the genomes containing all genes required for complete de novo folate synthesis. An additional 39% of the genomes had the genetic capacity to synthesize folates in the presence of pABA, an upstream intermediate that can be obtained through diet or from other intestinal microbes. Bacterial folate synthesis was assessed during exponential and stationary phase growth through the evaluation of expression of select folate synthesis genes, quantification of total folate production, and analysis of folate polyglutamylation. Increased expression of key folate synthesis genes was apparent in exponential phase, and increased folate polyglutamylation occurred during late stationary phase. Of the folate producers, we focused on the commensal Lactobacillus reuteri to examine host-microbe interactions in relation to folate and examined folate receptors in the physiologically relevant human enteroid model. RNAseq data revealed segment-specific folate receptor distribution. Treatment of human colonoid monolayers with conditioned media (CM) from wild-type L. reuteri did not influence the expression of key folate transporters proton-coupled folate transporter (PCFT) or reduced folate carrier (RFC). However, CM from L. reuteri containing a site-specific inactivation of the folC gene, which prevents the bacteria from synthesizing a polyglutamate tail on folate, significantly upregulated RFC expression. No effects were observed using L. reuteri with a site inactivation of folC2, which results in no folate production. This work sheds light on the contributions of microbial folate to overall folate status and mammalian host metabolism.}, }
@article {pmid31649168, year = {2019}, author = {Sonnenburg, JL and Sonnenburg, ED}, title = {Vulnerability of the industrialized microbiota.}, journal = {Science (New York, N.Y.)}, volume = {366}, number = {6464}, pages = {}, doi = {10.1126/science.aaw9255}, pmid = {31649168}, issn = {1095-9203}, support = {DP1 AT009892/AT/NCCIH NIH HHS/United States ; R01 DK085025/DK/NIDDK NIH HHS/United States ; }, mesh = {Anti-Bacterial Agents ; Bacteria/*classification ; Ecosystem ; Food ; *Gastrointestinal Microbiome ; Humans ; *Industrial Development ; Life Style ; Sanitation ; }, abstract = {The human body is an ecosystem that is home to a complex array of microbes known as the microbiome or microbiota. This ecosystem plays an important role in human health, but as a result of recent lifestyle changes occurring around the planet, whole populations are seeing a major shift in their gut microbiota. Measures meant to kill or limit exposure to pathogenic microbes, such as antibiotics and sanitation, combined with other factors such as processed food, have had unintended consequences for the human microbial ecosystem, including changes that may be difficult to reverse. Microbiota alteration and the accompanying loss of certain functional attributes might result in the microbial communities of people living in industrialized societies being suboptimal for human health. As macroecologists, conservationists, and climate scientists race to document, understand, predict, and delay global changes in our wider environment, microbiota scientists may benefit by using analogous approaches to study and protect our intimate microbial ecosystems.}, }
@article {pmid31647664, year = {2019}, author = {Hellweger, FL and Vick, C and Rückbeil, F and Bucci, V}, title = {Fresh Ideas Bloom in Gut Healthcare to Cross-Fertilize Lake Management.}, journal = {Environmental science &amp; technology}, volume = {53}, number = {24}, pages = {14099-14112}, doi = {10.1021/acs.est.9b04218}, pmid = {31647664}, issn = {1520-5851}, mesh = {*Cyanobacteria ; Ecosystem ; Humans ; Lakes ; *Microcystis ; }, abstract = {Harmful bacteria may be the most significant threat to human gut and lake ecosystem health, and they are often managed using similar tools, like poisoning with antibiotics or algicides. Out-of-the-box thinking in human microbiome engineering is leading to novel methods, like engineering bacteria to kill pathogens, "persuade" them not to produce toxins, or "mop up" their toxins. The bacterial agent can be given a competitive edge via an exclusive nutrient, and they can be engineered to commit suicide once their work is done. Viruses can kill pathogens with specific DNA sequences or knock out their antibiotic resistance genes using CRISPR technology. Some of these ideas may work for lakes. We critically review novel methods for managing harmful bacteria in the gut from the perspective of managing toxic cyanobacteria in lakes, and discuss practical aspects such as modifying bacteria using genetic engineering or directed evolution, mass culturing and controlling the agents. A key knowledge gap is in the ecology of strains, like toxigenic vs nontoxigenic Microcystis, including allelopathic and Black Queen interactions. Some of the "gut methods" may have future potential for lakes, but there presently is no substitute for established management approaches, including reducing N and P nutrient inputs, and mitigating climate change.}, }
@article {pmid31639026, year = {2019}, author = {Greathouse, KL and Sinha, R and Vogtmann, E}, title = {DNA extraction for human microbiome studies: the issue of standardization.}, journal = {Genome biology}, volume = {20}, number = {1}, pages = {212}, pmid = {31639026}, issn = {1474-760X}, mesh = {DNA/*isolation &amp; purification/standards ; Feces/chemistry ; Genomics/*standards ; Humans ; *Microbiota ; }, abstract = {Among the laboratory and bioinformatic processing steps for human microbiome studies, a lack of consistency in DNA extraction methodologies is hindering the ability to compare results between studies and sometimes leading to errant conclusions. The purpose of this article is to highlight the issues related to DNA extraction methods and to suggest minimum standard requirements that should be followed to ensure consistency and reproducibility.}, }
@article {pmid31636011, year = {2019}, author = {Altay, O and Nielsen, J and Uhlen, M and Boren, J and Mardinoglu, A}, title = {Systems biology perspective for studying the gut microbiota in human physiology and liver diseases.}, journal = {EBioMedicine}, volume = {49}, number = {}, pages = {364-373}, pmid = {31636011}, issn = {2352-3964}, mesh = {*Gastrointestinal Microbiome ; Humans ; Liver Diseases/*microbiology/*physiopathology ; Metabolism ; *Microbiota ; Pharmaceutical Preparations/metabolism ; *Systems Biology ; }, abstract = {The advancement in high-throughput sequencing technologies and systems biology approaches have revolutionized our understanding of biological systems and opened a new path to investigate unacknowledged biological phenomena. In parallel, the field of human microbiome research has greatly evolved and the relative contribution of the gut microbiome to health and disease have been systematically explored. This review provides an overview of the network-based and translational systems biology-based studies focusing on the function and composition of gut microbiota. We also discussed the association between the gut microbiome and the overall human physiology, as well as hepatic diseases and other metabolic disorders.}, }
@article {pmid31635533, year = {2020}, author = {Renson, A and Herd, P and Dowd, JB}, title = {Sick Individuals and Sick (Microbial) Populations: Challenges in Epidemiology and the Microbiome.}, journal = {Annual review of public health}, volume = {41}, number = {}, pages = {63-80}, pmid = {31635533}, issn = {1545-2093}, support = {P2C HD050924/HD/NICHD NIH HHS/United States ; R21 AI121784/AI/NIAID NIH HHS/United States ; T32 HD091058/HD/NICHD NIH HHS/United States ; }, mesh = {Confounding Factors, Epidemiologic ; Epidemiology/*organization &amp; administration ; *Ethnicity ; Gastrointestinal Microbiome/*physiology ; Humans ; Metabolic Diseases/*epidemiology/ethnology ; Microbiota/physiology ; *Racial Groups ; Social Environment ; Socioeconomic Factors ; }, abstract = {The human microbiome represents a new frontier in understanding the biology of human health. While epidemiology in this area is still in its infancy, its scope will likely expand dramatically over the coming years. To rise to the challenge, we argue that epidemiology should capitalize on its population perspective as a critical complement to molecular microbiome research, allowing for the illumination of contextual mechanisms that may vary more across populations rather than among individuals. We first briefly review current research on social context and the gut microbiome, focusing specifically on socioeconomic status (SES) and race/ethnicity. Next, we reflect on the current state of microbiome epidemiology through the lens of one specific area, the association of the gut microbiome and metabolic disorders. We identify key methodological shortcomings of current epidemiological research in this area, including extensive selection bias, the use of noncompositionally robust measures, and a lack of attention to social factors as confounders or effect modifiers.}, }
@article {pmid31633390, year = {2019}, author = {Baker, JL and He, X and Shi, W}, title = {Precision Reengineering of the Oral Microbiome for Caries Management.}, journal = {Advances in dental research}, volume = {30}, number = {2}, pages = {34-39}, pmid = {31633390}, issn = {1544-0737}, support = {F32 DE026947/DE/NIDCR NIH HHS/United States ; R01 DE020102/DE/NIDCR NIH HHS/United States ; R01 DE023810/DE/NIDCR NIH HHS/United States ; R01 DE026186/DE/NIDCR NIH HHS/United States ; }, mesh = {Biofilms ; *Dental Caries ; *Dental Plaque ; Humans ; *Microbiota ; Streptococcus mutans ; }, abstract = {Technological advancements have revolutionized our understanding of the complexity and importance of the human microbiome. This progress has also emphasized the need for precision therapeutics, as it has underscored the dilemmas, such as dysbiosis and increasing antibiotic resistance, associated with current, broad-spectrum treatment modalities. Dental caries remains the most common chronic disease worldwide, accompanied by a tremendous financial and social burden, despite widespread and efficacious fluoride and hygienic regimens. Over the past several decades, various precision approaches to combat dental caries, including vaccines, probiotics, and antimicrobial compounds, have been pursued. Despite the distinct overall conceptual strengths of each approach, for various reasons, there are currently no approved precision antibiotic therapeutics to prevent dental caries. Specifically targeted antimicrobial peptides (STAMPs) are synthetic molecules that combine the antibiotic moiety of a traditional antimicrobial peptide with a targeting domain to provide specificity against a particular organism. Conjoining the killing domain from the antimicrobial, novispirin G10, and a targeting domain derived from the Streptococcus mutans pheromone, CSP, the STAMP C16G2 was designed to provide targeted killing of S. mutans, widely considered the keystone species in dental caries pathogenesis. C16G2 was able to selectively eliminate S. mutans from complex ecosystems while leaving closely related, yet health-associated, oral species unharmed. This remodeling of the dental plaque community is expected to have significant advantages compared to conventional broad-spectrum mouthwashes, as the intact, surviving community is apt to prevent reinfection by pathogens. Following successful phase I clinical trials that evaluated the safety and basic microbiology of C16G2 treatments, the phase II trials of several C16G2 formulations are currently in progress. C16G2 represents an exciting advance in precision therapeutics, and the STAMP platform provides vast opportunities for both the development of additional therapeutics and the overall study of microbial ecology.}, }
@article {pmid31629686, year = {2019}, author = {Cao, L and Gurevich, A and Alexander, KL and Naman, CB and Leão, T and Glukhov, E and Luzzatto-Knaan, T and Vargas, F and Quinn, R and Bouslimani, A and Nothias, LF and Singh, NK and Sanders, JG and Benitez, RAS and Thompson, LR and Hamid, MN and Morton, JT and Mikheenko, A and Shlemov, A and Korobeynikov, A and Friedberg, I and Knight, R and Venkateswaran, K and Gerwick, WH and Gerwick, L and Dorrestein, PC and Pevzner, PA and Mohimani, H}, title = {MetaMiner: A Scalable Peptidogenomics Approach for Discovery of Ribosomal Peptide Natural Products with Blind Modifications from Microbial Communities.}, journal = {Cell systems}, volume = {9}, number = {6}, pages = {600-608.e4}, pmid = {31629686}, issn = {2405-4720}, support = {R01 GM118815/GM/NIGMS NIH HHS/United States ; R01 GM107550/GM/NIGMS NIH HHS/United States ; P41 GM103484/GM/NIGMS NIH HHS/United States ; R01 GM097509/GM/NIGMS NIH HHS/United States ; T32 CA009523/CA/NCI NIH HHS/United States ; DP2 GM137413/GM/NIGMS NIH HHS/United States ; R01 GM065490/GM/NIGMS NIH HHS/United States ; }, mesh = {Computational Biology/*methods ; Genomics/methods ; Humans ; Microbiota/*genetics ; Peptides/chemistry ; Protein Processing, Post-Translational/*genetics ; Ribosomes/genetics ; Software ; }, abstract = {Ribosomally synthesized and post-translationally modified peptides (RiPPs) are an important class of natural products that contain antibiotics and a variety of other bioactive compounds. The existing methods for discovery of RiPPs by combining genome mining and computational mass spectrometry are limited to discovering specific classes of RiPPs from small datasets, and these methods fail to handle unknown post-translational modifications. Here, we present MetaMiner, a software tool for addressing these challenges that is compatible with large-scale screening platforms for natural product discovery. After searching millions of spectra in the Global Natural Products Social (GNPS) molecular networking infrastructure against just eight genomic and metagenomic datasets, MetaMiner discovered 31 known and seven unknown RiPPs from diverse microbial communities, including human microbiome and lichen microbiome, and microorganisms isolated from the International Space Station.}, }
@article {pmid31623122, year = {2019}, author = {Dobrange, E and Peshev, D and Loedolff, B and Van den Ende, W}, title = {Fructans as Immunomodulatory and Antiviral Agents: The Case of Echinacea.}, journal = {Biomolecules}, volume = {9}, number = {10}, pages = {}, pmid = {31623122}, issn = {2218-273X}, mesh = {Antioxidants/chemistry/isolation &amp; purification/*pharmacology ; Antiviral Agents/chemistry/isolation &amp; purification/*pharmacology ; Echinacea/*chemistry ; Fructans/chemistry/isolation &amp; purification/*pharmacology ; Immune System/drug effects/immunology ; *Immunomodulation ; Plant Extracts/chemistry/isolation &amp; purification/pharmacology ; Viruses/*drug effects/immunology ; }, abstract = {Throughout history, medicinal purposes of plants have been studied, documented, and acknowledged as an integral part of human healthcare systems. The development of modern medicine still relies largely on this historical knowledge of the use and preparation of plants and their extracts. Further research into the human microbiome highlights the interaction between immunomodulatory responses and plant-derived, prebiotic compounds. One such group of compounds includes the inulin-type fructans (ITFs), which may also act as signaling molecules and antioxidants. These multifunctional compounds occur in a small proportion of plants, many of which have recognized medicinal properties. Echinacea is a well-known medicinal plant and products derived from it are sold globally for its cold- and flu-preventative and general health-promoting properties. Despite the well-documented phytochemical profile of Echinacea plants and products, little research has looked into the possible role of ITFs in these products. This review aims to highlight the occurrence of ITFs in Echinacea derived formulations and the potential role they play in immunomodulation.}, }
@article {pmid31622559, year = {2020}, author = {Van Treuren, W and Dodd, D}, title = {Microbial Contribution to the Human Metabolome: Implications for Health and Disease.}, journal = {Annual review of pathology}, volume = {15}, number = {}, pages = {345-369}, pmid = {31622559}, issn = {1553-4014}, support = {K08 DK110335/DK/NIDDK NIH HHS/United States ; }, mesh = {Diet ; Gastrointestinal Microbiome/*physiology ; Gastrointestinal Tract/metabolism/microbiology ; *Health ; Humans ; Metabolic Diseases/etiology/*microbiology ; Metabolome/*physiology ; }, abstract = {The human gastrointestinal tract is home to an incredibly dense population of microbes. These microbes employ unique strategies to capture energy in this largely anaerobic environment. In the process of breaking down dietary- and host-derived substrates, the gut microbiota produce a broad range of metabolic products that accumulate to high levels in the gut. Increasingly, studies are revealing that these chemicals impact host biology, either by acting on cells within the gastrointestinal tract or entering circulation and exerting their effects at distal sites within the body. Given the high level of functional diversity in the gut microbiome and the varied diets that we consume, the repertoire of microbiota-derived molecules within our bodies varies dramatically across individuals. Thus, the microbes in our gut and the metabolic end products they produce represent a phenotypic lever that we can potentially control to develop new therapeutics for personalized medicine. Here, we review current understanding of how microbes in the gastrointestinal tract contribute to the molecules within our gut and those that circulate within our bodies. We also highlight examples of how these molecules affect host physiology and discuss potential strategies for controlling their production to promote human health and to treat disease.}, }
@article {pmid31617360, year = {2019}, author = {Lam, KL and Cheung, PC}, title = {Carbohydrate-Based Prebiotics in Targeted Modulation of Gut Microbiome.}, journal = {Journal of agricultural and food chemistry}, volume = {67}, number = {45}, pages = {12335-12340}, doi = {10.1021/acs.jafc.9b04811}, pmid = {31617360}, issn = {1520-5118}, mesh = {Animals ; Bacteria/classification/genetics/isolation &amp; purification/metabolism ; Carbohydrates/chemistry/*pharmacology ; Gastrointestinal Microbiome/*drug effects ; Humans ; Intestines/microbiology ; Prebiotics/*analysis ; }, abstract = {The Human Microbiome Project has prompted unprecedented advancement in microbiome science. Personalized microbiome modulation with precision (PMMP) is one of the emerging yet challenging fields in microbiome research. Carbohydrate-based prebiotics (CBPs) have been shown to modulate the gut microbiome to various extents according to different structural characteristics, such as degree of polymerization, branching, glycosidic linkage, monosaccharide profile, and chemical modification. Subsequently, a targeted modulation of the microbiome might be achieved by using CBPs with a specific structure. A multidimensional database can be established based on the structure-microbiome and structure-microbial-marker relationships. Such relationships could facilitate the development of synbiotics and PMMP.}, }
@article {pmid31617205, year = {2020}, author = {Sharma, A and Das, P and Buschmann, M and Gilbert, JA}, title = {The Future of Microbiome-Based Therapeutics in Clinical Applications.}, journal = {Clinical pharmacology and therapeutics}, volume = {107}, number = {1}, pages = {123-128}, doi = {10.1002/cpt.1677}, pmid = {31617205}, issn = {1532-6535}, mesh = {Animals ; Drug-Related Side Effects and Adverse Reactions/etiology/*prevention &amp; control ; Fecal Microbiota Transplantation/methods ; Humans ; Microbiota/*physiology ; Pharmaceutical Preparations/*metabolism ; Probiotics/administration &amp; dosage ; }, abstract = {The microbiome, a collection of microorganisms, their genomes, and the surrounding environmental conditions, is akin to a human organ, and knowledge is emerging on its role in human health and diseases. The influence of the microbiome in drug response has only been investigated in detail for the last 10 years. The human microbiome is a complex and highly dynamic system, which varies dramatically between individuals, yet there exists a common core microbiome that is heritable and can be transmitted to progeny. Here, we review the role of the human microbiome, which is now widely accepted as a major factor that drives the interpersonal variation in therapeutic response. We describe examples in which the microbiome modifies drug action. Despite its complexity, the microbiome can be readily altered, with the potential to increase the benefits and reduce the toxicity and side effects associated with pharmaceutical drugs. The potential of new microbiome-based strategies, such as fecal microbiota transplant, probiotics, and phage therapy, as promising medical therapeutics are outlined. We also suggest a combination reductionist and system-level approaches that could be applied to further investigate the role of microbiota in drug metabolism modulation of drug response. Finally, we emphasize the importance of combining microbiome and pharmacology studies as a novel means to treat disease and reduce side effects.}, }
@article {pmid31616466, year = {2019}, author = {Srivastava, D and Baksi, KD and Kuntal, BK and Mande, SS}, title = {"EviMass": A Literature Evidence-Based Miner for Human Microbial Associations.}, journal = {Frontiers in genetics}, volume = {10}, number = {}, pages = {849}, pmid = {31616466}, issn = {1664-8021}, abstract = {The importance of understanding microbe-microbe as well as microbe-disease associations is one of the key thrust areas in human microbiome research. High-throughput metagenomic and transcriptomic projects have fueled discovery of a number of new microbial associations. Consequently, a plethora of information is being added routinely to biomedical literature, thereby contributing toward enhancing our knowledge on microbial associations. In this communication, we present a tool called "EviMass" (Evidence based mining of human Microbial Associations), which can assist biologists to validate their predicted hypotheses from new microbiome studies. Users can interactively query the processed back-end database for microbe-microbe and disease-microbe associations. The EviMass tool can also be used to upload microbial association networks generated from a human "disease-control" microbiome study and validate the associations from biomedical literature. Additionally, a list of differentially abundant microbes for the corresponding disease can be queried in the tool for reported evidences. The results are presented as graphical plots, tabulated summary, and other evidence statistics. EviMass is a comprehensive platform and is expected to enable microbiome researchers not only in mining microbial associations, but also enriching a new research hypothesis. The tool is available free for academic use at https://web.rniapps.net/evimass.}, }
@article {pmid31608855, year = {2019}, author = {Lilley, ECH and Morris, AT and Silberg, JL}, title = {The Mid-Atlantic Twin Registry of Virginia Commonwealth University.}, journal = {Twin research and human genetics : the official journal of the International Society for Twin Studies}, volume = {22}, number = {6}, pages = {753-756}, doi = {10.1017/thg.2019.87}, pmid = {31608855}, issn = {1832-4274}, mesh = {Bullying ; Cardiovascular Diseases/genetics/history ; Epigenesis, Genetic ; Female ; History, 20th Century ; History, 21st Century ; Humans ; Male ; Neoplasms/genetics/history ; *Registries ; Smoking/genetics/history ; Substance-Related Disorders/genetics/history ; Twins/*genetics ; Universities ; Virginia ; }, abstract = {The Mid-Atlantic Twin Registry (MATR) is a population-based registry of more than 60,000 twins primarily born or living in Virginia, North Carolina and South Carolina. Researchers may utilize the MATR for administration of research services, including study recruitment, data or sample (e.g., DNA) collection, archival dataset creation, as well as data collection through mailed, phone or online surveys. In addition, the MATR houses the MATR Repository, with over 1700 DNA samples primarily from whole blood available for researchers interested in DNA genotyping. For over 40 years MATR twins have participated in research studies with investigators from a range of scientific disciplines and institutions. These studies, which have resulted in numerous publications, explored diverse topics, including substance use, smoking behaviors, developmental psychopathology, bullying, children's health, cardiovascular disease, cancer, the human microbiome, epigenetics of aging, children of twins and sleep homeostasis. Researchers interested in utilizing twins are encouraged to contact the MATR to discuss potential research opportunities.}, }
@article {pmid31608406, year = {2020}, author = {Farmakiotis, D}, title = {The Human Microbiome and Checkpoint Inhibition: Potential Benefits From Antibiotic Stewardship.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {71}, number = {3}, pages = {701-702}, doi = {10.1093/cid/ciz1003}, pmid = {31608406}, issn = {1537-6591}, mesh = {Anti-Bacterial Agents/therapeutic use ; *Antimicrobial Stewardship ; Humans ; *Microbiota ; }, }
@article {pmid31608279, year = {2019}, author = {Kang, W and Jia, Z and Tang, D and Zhao, X and Shi, J and Jia, Q and He, K and Feng, Q}, title = {Time-Course Transcriptome Analysis for Drug Repositioning in Fusobacterium nucleatum-Infected Human Gingival Fibroblasts.}, journal = {Frontiers in cell and developmental biology}, volume = {7}, number = {}, pages = {204}, pmid = {31608279}, issn = {2296-634X}, abstract = {Fusobacterium nucleatum (F. nucleatum) is a crucial periodontal pathogen and human gingival fibroblasts (GFs) are the first line of defense against oral pathogens. However, the research on potential molecular mechanisms of host defense and effective treatment of F. nucleatum infection in GFs remains scarce. In this study, we undertook a time-series experiment and performed an RNA-seq analysis to explore gene expression profiles during the process of F. nucleatum infection in GFs. Differentially expressed genes (DEGs) could be divided into three coexpression clusters. Functional analysis revealed that the immune-related signaling pathways were more overrepresented at the early stage, while metabolic pathways were mainly enriched at the late stage. We computationally identified several U.S. Food and Drug Administration (FDA)-approved drugs that could protect the F. nucleatum infected GFs via a coexpression-based drug repositioning approach. Biologically, we confirmed that six drugs (etravirine, zalcitabine, wortmannin, calcium D-pantothenate, ellipticine, and tanespimycin) could significantly decrease F. nucleatum-induced reactive oxygen species (ROS) generation and block the Protein Kinase B (PKB/AKT)/mitogen-activated protein kinase signaling pathways. Our study provides more detailed molecular mechanisms of the process by which F. nucleatum infects GFs and illustrates the value of the cogena-based drug repositioning method and the potential therapeutic application of these tested drugs in the treatment of F. nucleatum infection.}, }
@article {pmid31607556, year = {2019}, author = {Tett, A and Huang, KD and Asnicar, F and Fehlner-Peach, H and Pasolli, E and Karcher, N and Armanini, F and Manghi, P and Bonham, K and Zolfo, M and De Filippis, F and Magnabosco, C and Bonneau, R and Lusingu, J and Amuasi, J and Reinhard, K and Rattei, T and Boulund, F and Engstrand, L and Zink, A and Collado, MC and Littman, DR and Eibach, D and Ercolini, D and Rota-Stabelli, O and Huttenhower, C and Maixner, F and Segata, N}, title = {The Prevotella copri Complex Comprises Four Distinct Clades Underrepresented in Westernized Populations.}, journal = {Cell host &amp; microbe}, volume = {26}, number = {5}, pages = {666-679.e7}, pmid = {31607556}, issn = {1934-6069}, support = {TL1 TR001447/TR/NCATS NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; U54 DE023798/DE/NIDCR NIH HHS/United States ; 716575/ERC_/European Research Council/International ; R24 DK110499/DK/NIDDK NIH HHS/United States ; R01 DK103358/DK/NIDDK NIH HHS/United States ; R01 HG005220/HG/NHGRI NIH HHS/United States ; }, mesh = {Diet ; Ethiopia ; Feces/microbiology ; Fossils/*microbiology ; Gastrointestinal Microbiome/*genetics ; Genetic Variation ; Genome, Bacterial/*genetics ; Ghana ; Humans ; Prevotella/*classification/*genetics/isolation &amp; purification ; Tanzania ; }, abstract = {Prevotella copri is a common human gut microbe that has been both positively and negatively associated with host health. In a cross-continent meta-analysis exploiting >6,500 metagenomes, we obtained >1,000 genomes and explored the genetic and population structure of P. copri. P. copri encompasses four distinct clades (>10% inter-clade genetic divergence) that we propose constitute the P. copri complex, and all clades were confirmed by isolate sequencing. These clades are nearly ubiquitous and co-present in non-Westernized populations. Genomic analysis showed substantial functional diversity in the complex with notable differences in carbohydrate metabolism, suggesting that multi-generational dietary modifications may be driving reduced prevalence in Westernized populations. Analysis of ancient metagenomes highlighted patterns of P. copri presence consistent with modern non-Westernized populations and a clade delineation time pre-dating human migratory waves out of Africa. These findings reveal that P. copri exhibits a high diversity that is underrepresented in Western-lifestyle populations.}, }
@article {pmid31603985, year = {2020}, author = {McCrory, C and Fiorito, G and McLoughlin, S and Polidoro, S and Cheallaigh, CN and Bourke, N and Karisola, P and Alenius, H and Vineis, P and Layte, R and Kenny, RA}, title = {Epigenetic Clocks and Allostatic Load Reveal Potential Sex-Specific Drivers of Biological Aging.}, journal = {The journals of gerontology. Series A, Biological sciences and medical sciences}, volume = {75}, number = {3}, pages = {495-503}, doi = {10.1093/gerona/glz241}, pmid = {31603985}, issn = {1758-535X}, support = {MR/S019669/1/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Aged ; Aging/*genetics ; *Allostasis ; Cross-Sectional Studies ; *Epigenesis, Genetic ; Female ; Humans ; Longitudinal Studies ; Male ; Middle Aged ; Sex Factors ; }, abstract = {Allostatic load (AL) and epigenetic clocks both attempt to characterize the accelerated aging of biological systems, but at present it is unclear whether these measures are complementary or distinct. This study examines the cross-sectional association of AL with epigenetic age acceleration (EAA) in a subsample of 490 community-dwelling older adults participating in The Irish Longitudinal study on Aging (TILDA). A battery of 14 biomarkers representing the activity of four different physiological systems: immunological, cardiovascular, metabolic, renal, was used to construct the AL score. DNA methylation age was computed according to the algorithms described by Horvath, Hannum, and Levine allowing for estimation of whether an individual is experiencing accelerated or decelerated aging. Horvath, Hannum, and Levine EAA correlated 0.05, 0.03, and 0.21 with AL, respectively. Disaggregation by sex revealed that AL was more strongly associated with EAA in men compared with women as assessed using Horvath's clock. Metabolic dysregulation was a strong driver of EAA in men as assessed using Horvath and Levine's clock, while metabolic and cardiovascular dysregulation were associated with EAA in women using Levine's clock. Results indicate that AL and the epigenetic clocks are measuring different age-related variance and implicate sex-specific drivers of biological aging.}, }
@article {pmid31601287, year = {2020}, author = {Stinson, LF}, title = {Establishment of the early-life microbiome: a DOHaD perspective.}, journal = {Journal of developmental origins of health and disease}, volume = {11}, number = {3}, pages = {201-210}, doi = {10.1017/S2040174419000588}, pmid = {31601287}, issn = {2040-1752}, mesh = {Anti-Bacterial Agents/*adverse effects ; Bottle Feeding/*adverse effects ; Breast Feeding ; Child Development/*physiology ; Dysbiosis/chemically induced/microbiology/*physiopathology ; Gastrointestinal Microbiome/drug effects/*physiology ; Humans ; Infant ; Infant, Newborn ; }, abstract = {The human microbiome plays a number of critical roles in host physiology. Evidence from longitudinal cohort studies and animal models strongly supports the theory that maldevelopment of the microbiome in early life can programme later-life disease. The early-life microbiome develops in a clear stepwise manner over the first 3 years of life. During this highly dynamic time, insults such as antibiotic use and formula feeding can adversely affect the composition and temporal development of the microbiome. Such experiences predispose infants for the development of chronic health conditions later in life. This review highlights key factors that disrupt the early-life microbiome and highlights major non-communicable diseases which are underpinned by early-life dysbiosis.}, }
@article {pmid31600503, year = {2019}, author = {Shkoporov, AN and Clooney, AG and Sutton, TDS and Ryan, FJ and Daly, KM and Nolan, JA and McDonnell, SA and Khokhlova, EV and Draper, LA and Forde, A and Guerin, E and Velayudhan, V and Ross, RP and Hill, C}, title = {The Human Gut Virome Is Highly Diverse, Stable, and Individual Specific.}, journal = {Cell host &amp; microbe}, volume = {26}, number = {4}, pages = {527-541.e5}, doi = {10.1016/j.chom.2019.09.009}, pmid = {31600503}, issn = {1934-6069}, mesh = {Bacteroides/isolation &amp; purification/*virology ; Faecalibacterium/isolation &amp; purification/*virology ; Gastrointestinal Microbiome/*genetics ; Humans ; Longitudinal Studies ; Metagenome/genetics ; Microviridae/classification/*genetics/isolation &amp; purification ; Prevotella/isolation &amp; purification/*virology ; Viral Load ; }, abstract = {The human gut contains a vast array of viruses, mostly bacteriophages. The majority remain uncharacterized, and their roles in shaping the gut microbiome and in impacting on human health remain poorly understood. We performed longitudinal metagenomic analysis of fecal viruses in healthy adults that reveal high temporal stability, individual specificity, and correlation with the bacterial microbiome. Using a database-independent approach that uses most of the sequencing data, we uncovered the existence of a stable, numerically predominant individual-specific persistent personal virome. Clustering of viral genomes and de novo taxonomic annotation identified several groups of crAss-like and Microviridae bacteriophages as the most stable colonizers of the human gut. CRISPR-based host prediction highlighted connections between these stable viral communities and highly predominant gut bacterial taxa such as Bacteroides, Prevotella, and Faecalibacterium. This study provides insights into the structure of the human gut virome and serves as an important baseline for hypothesis-driven research.}, }
@article {pmid31600337, year = {2019}, author = {Andreev, VP and Liu, G and Zee, J and Henn, L and Flores, GE and Merion, RM}, title = {Clustering of the structures by using "snakes-&amp;-dragons" approach, or correlation matrix as a signal.}, journal = {PloS one}, volume = {14}, number = {10}, pages = {e0223267}, pmid = {31600337}, issn = {1932-6203}, mesh = {Adolescent ; Adult ; *Algorithms ; Brain/physiology ; Cluster Analysis ; Computer Simulation ; Female ; Genomics ; Humans ; Male ; Microbiota ; Nerve Net/physiology ; Young Adult ; }, abstract = {Biological, ecological, social, and technological systems are complex structures with multiple interacting parts, often represented by networks. Correlation matrices describing interdependency of the variables in such structures provide key information for comparison and classification of such systems. Classification based on correlation matrices could supplement or improve classification based on variable values, since the former reveals similarities in system structures, while the latter relies on the similarities in system states. Importantly, this approach of clustering correlation matrices is different from clustering elements of the correlation matrices, because our goal is to compare and cluster multiple networks-not the nodes within the networks. A novel approach for clustering correlation matrices, named "snakes-&amp;-dragons," is introduced and illustrated by examples from neuroscience, human microbiome, and macroeconomics.}, }
@article {pmid31597320, year = {2019}, author = {Holster, S and Hooiveld, GJ and Repsilber, D and Vos, WM and Brummer, RJ and König, J}, title = {Allogenic Faecal Microbiota Transfer Induces Immune-Related Gene Sets in the Colon Mucosa of Patients with Irritable Bowel Syndrome.}, journal = {Biomolecules}, volume = {9}, number = {10}, pages = {}, pmid = {31597320}, issn = {2218-273X}, mesh = {Adult ; Bacteria/*classification/immunology ; Double-Blind Method ; Fecal Microbiota Transplantation/*methods ; Female ; Gastrointestinal Microbiome ; Gene Expression Profiling/*methods ; Gene Expression Regulation ; Gene Regulatory Networks ; Humans ; *Immunity ; Intestinal Mucosa/chemistry ; Irritable Bowel Syndrome/genetics/immunology/*therapy ; Male ; Middle Aged ; Quality of Life ; Sequence Analysis, RNA ; Sigmoidoscopy ; Transplantation, Autologous ; Transplantation, Homologous ; Treatment Outcome ; }, abstract = {Faecal microbiota transfer (FMT) consists of the introduction of new microbial communities into the intestine of a patient, with the aim of restoring a disturbed gut microbiota. Even though it is used as a potential treatment for various diseases, it is unknown how the host mucosa responds to FMT. This study aims to investigate the colonic mucosa gene expression response to allogenic (from a donor) or autologous (own) FMT in patients with irritable bowel syndrome (IBS). In a recently conducted randomised, double-blinded, controlled clinical study, 17 IBS patients were treated with FMT by colonoscopy. RNA was isolated from colonic biopsies collected by sigmoidoscopy at baseline, as well as two weeks and eight weeks after FMT. In patients treated with allogenic FMT, predominantly immune response-related gene sets were induced, with the strongest response two weeks after the FMT. In patients treated with autologous FMT, predominantly metabolism-related gene sets were affected. Furthermore, several microbiota genera showed correlations with immune-related gene sets, with different correlations found after allogenic compared to autologous FMT. This study shows that the microbe-host response is influenced by FMT on the mucosal gene expression level, and that there are clear differences in response to allogenic compared to autologous FMT.}, }
@article {pmid31594829, year = {2019}, author = {Zhao, H and Fu, S and Yu, Y and Zhang, Z and Li, P and Ma, Q and Jia, W and Ning, K and Qu, S and Liu, Q}, title = {MetaMed: Linking Microbiota Functions with Medicine Therapeutics.}, journal = {mSystems}, volume = {4}, number = {5}, pages = {}, pmid = {31594829}, issn = {2379-5077}, abstract = {Understanding how the human microbiome affects human health has consequences for treating disease and minimizing unwanted side effects in clinical research. Here, we present MetaMed (http://metamed.rwebox.com/index), a novel and integrative system-wide correlation mapping system to link bacterial functions and medicine therapeutics, providing novel hypotheses for deep investigation of microbe therapeutic effects on human health. Furthermore, comprehensive relationships between microbes living in the environment and drugs were discovered, providing a rich source for discovering microbiota metabolites with great potential for pharmaceutical applications.}, }
@article {pmid31592582, year = {2019}, author = {Li, W and Ma, ZS}, title = {Diversity scaling of human vaginal microbial communities.}, journal = {Zoological research}, volume = {40}, number = {6}, pages = {587-594}, pmid = {31592582}, issn = {2095-8137}, mesh = {Bacteria/*classification ; Female ; Humans ; Microbiota ; Postpartum Period ; Vagina/*microbiology ; }, abstract = {The composition and diversity of the human vaginal microbial community have been investigated intensively due to the diversity-stability relationship (DSR)-based hypothesis for bacterial vaginosis (BV) etiology, which was first proposed in the 1990s and has received renewed interest in recent years. Nevertheless, diversity changes (scaling) across individuals in a cohort or population have not yet been addressed, which is significant both theoretically and practically. Theoretically, biodiversity scaling is the core of biogeography, and practically, inter-subject heterogeneity is critical for understanding the etiology and epidemiology of human microbiome-associated diseases such as BV. Here we applied the diversity-area relationship (DAR), a recent extension to the classic species-area relationship (SAR), to study diversity scaling of the vaginal microbiome by reanalyzing reported data collected from 1 107 postpartum women. The model used here characterized the power-law (or its extension) relationships between accrued diversity and areas (numbers of individuals), upon which four biogeographic profiles were thus defined. Specifically, we established the DAR profile (relationship between diversity scaling parameter and so-termed diversity order (q)), similarly pair-wise diversity overlap (PDO) profile, maximal accrual diversity (MAD) profile, and ratio of individual-level to population-level diversity (RIP) profile. These four profiles offer valuable tools to assess and predict diversity scaling (changes) in the human vaginal microbiome across individuals, as well as to understand the dynamics of vaginal microbiomes in healthy women.}, }
@article {pmid31590679, year = {2019}, author = {Amato, KR and Mallott, EK and McDonald, D and Dominy, NJ and Goldberg, T and Lambert, JE and Swedell, L and Metcalf, JL and Gomez, A and Britton, GAO and Stumpf, RM and Leigh, SR and Knight, R}, title = {Convergence of human and Old World monkey gut microbiomes demonstrates the importance of human ecology over phylogeny.}, journal = {Genome biology}, volume = {20}, number = {1}, pages = {201}, pmid = {31590679}, issn = {1474-760X}, mesh = {Animals ; Cercopithecidae/classification/genetics/microbiology ; Diet ; Ecosystem ; *Gastrointestinal Microbiome ; Hominidae/classification/genetics ; Humans ; Phylogeny ; RNA, Ribosomal, 16S/genetics ; }, abstract = {BACKGROUND: Comparative data from non-human primates provide insight into the processes that shaped the evolution of the human gut microbiome and highlight microbiome traits that differentiate humans from other primates. Here, in an effort to improve our understanding of the human microbiome, we compare gut microbiome composition and functional potential in 14 populations of humans from ten nations and 18 species of wild, non-human primates.<br><br>RESULTS: Contrary to expectations from host phylogenetics, we find that human gut microbiome composition and functional potential are more similar to those of cercopithecines, a subfamily of Old World monkey, particularly baboons, than to those of African apes. Additionally, our data reveal more inter-individual variation in gut microbiome functional potential within the human species than across other primate species, suggesting that the human gut microbiome may exhibit more plasticity in response to environmental variation compared to that of other primates.<br><br>CONCLUSIONS: Given similarities of ancestral human habitats and dietary strategies to those of baboons, these findings suggest that convergent ecologies shaped the gut microbiomes of both humans and cercopithecines, perhaps through environmental exposure to microbes, diet, and/or associated physiological adaptations. Increased inter-individual variation in the human microbiome may be associated with human dietary diversity or the ability of humans to inhabit novel environments. Overall, these findings show that diet, ecology, and physiological adaptations are more important than host-microbe co-diversification in shaping the human microbiome, providing a key foundation for comparative analyses of the role of the microbiome in human biology and health.}, }
@article {pmid31588499, year = {2020}, author = {Bradley, PH and Pollard, KS}, title = {phylogenize: correcting for phylogeny reveals genes associated with microbial distributions.}, journal = {Bioinformatics (Oxford, England)}, volume = {36}, number = {4}, pages = {1289-1290}, pmid = {31588499}, issn = {1367-4811}, mesh = {Humans ; *Microbiota ; Phylogeny ; RNA, Ribosomal, 16S ; }, abstract = {SUMMARY: Phylogenetic comparative methods are powerful but presently under-utilized ways to identify microbial genes underlying differences in community composition. These methods help to identify functionally important genes because they test for associations beyond those expected when related microbes occupy similar environments. We present phylogenize, a pipeline with web, QIIME 2 and R interfaces that allows researchers to perform phylogenetic regression on 16S amplicon and shotgun sequencing data and to visualize results. phylogenize applies broadly to both host-associated and environmental microbiomes. Using Human Microbiome Project and Earth Microbiome Project data, we show that phylogenize draws similar conclusions from 16S versus shotgun sequencing and reveals both known and candidate pathways associated with host colonization.<br><br>phylogenize is available at https://phylogenize.org and https://bitbucket.org/pbradz/phylogenize.<br><br>SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.}, }
@article {pmid31583780, year = {2020}, author = {Hooks, KB and O'Malley, MA}, title = {Contrasting Strategies: Human Eukaryotic Versus Bacterial Microbiome Research.}, journal = {The Journal of eukaryotic microbiology}, volume = {67}, number = {2}, pages = {279-295}, pmid = {31583780}, issn = {1550-7408}, mesh = {*Bacterial Physiological Phenomena ; Eukaryota/*physiology ; Humans ; *Microbiota ; Symbiosis/*physiology ; }, abstract = {Most discussions of human microbiome research have focused on bacterial investigations and findings. Our target is to understand how human eukaryotic microbiome research is developing, its potential distinctiveness, and how problems can be addressed. We start with an overview of the entire eukaryotic microbiome literature (578 papers), show tendencies in the human-based microbiome literature, and then compare the eukaryotic field to more developed human bacterial microbiome research. We are particularly concerned with problems of interpretation that are already apparent in human bacterial microbiome research (e.g. disease causality, probiotic interventions, evolutionary claims). We show where each field converges and diverges, and what this might mean for progress in human eukaryotic microbiome research. Our analysis then makes constructive suggestions for the future of the field.}, }
@article {pmid31582523, year = {2019}, author = {Sugimoto, Y and Camacho, FR and Wang, S and Chankhamjon, P and Odabas, A and Biswas, A and Jeffrey, PD and Donia, MS}, title = {A metagenomic strategy for harnessing the chemical repertoire of the human microbiome.}, journal = {Science (New York, N.Y.)}, volume = {366}, number = {6471}, pages = {}, doi = {10.1126/science.aax9176}, pmid = {31582523}, issn = {1095-9203}, support = {DP2 AI124441/AI/NIAID NIH HHS/United States ; }, mesh = {Host Microbial Interactions/*genetics ; Humans ; *Metagenome ; Metagenomics/*methods ; Microbiota/*genetics ; Multigene Family ; Polyketides/chemistry/*metabolism ; }, abstract = {Extensive progress has been made in determining the effects of the microbiome on human physiology and disease, but the underlying molecules and mechanisms governing these effects remain largely unexplored. Here, we combine a new computational algorithm with synthetic biology to access biologically active small molecules encoded directly in human microbiome-derived metagenomic sequencing data. We discover that members of a clinically used class of molecules are widely encoded in the human microbiome and that they exert potent antibacterial activities against neighboring microbes, implying a possible role in niche competition and host defense. Our approach paves the way toward a systematic unveiling of the chemical repertoire encoded by the human microbiome and provides a generalizable platform for discovering molecular mediators of microbiome-host and microbiome-microbiome interactions.}, }
@article {pmid31575764, year = {2019}, author = {Chmiel, JA and Daisley, BA and Burton, JP and Reid, G}, title = {Deleterious Effects of Neonicotinoid Pesticides on Drosophila melanogaster Immune Pathways.}, journal = {mBio}, volume = {10}, number = {5}, pages = {}, pmid = {31575764}, issn = {2150-7511}, mesh = {Animals ; Drosophila melanogaster/*drug effects/enzymology/immunology/microbiology ; Dual Oxidases/genetics/metabolism ; Female ; Hydrogen Peroxide/metabolism ; Immunity/drug effects ; Insecticides/*pharmacology ; Lactobacillus plantarum ; Male ; Neonicotinoids/*pharmacology ; Nitro Compounds/*pharmacology ; }, abstract = {Neonicotinoid insecticides are common agrochemicals that are used to kill pest insects and improve crop yield. However, sublethal exposure can exert unintentional toxicity to honey bees and other beneficial pollinators by dysregulating innate immunity. Generation of hydrogen peroxide (H2O2) by the dual oxidase (Duox) pathway is a critical component of the innate immune response, which functions to impede infection and maintain homeostatic regulation of the gut microbiota. Despite the importance of this pathway in gut immunity, the consequences of neonicotinoid exposure on Duox signaling have yet to be studied. Here, we use a Drosophila melanogaster model to investigate the hypothesis that imidacloprid (a common neonicotinoid) can affect the Duox pathway. The results demonstrated that exposure to sublethal imidacloprid reduced H2O2 production by inhibiting transcription of the Duox gene. Furthermore, the reduction in Duox expression was found to be a result of imidacloprid interacting with the midgut portion of the immune deficiency pathway. This impairment led to a loss of microbial regulation, as exemplified by a compositional shift and increased total abundance of Lactobacillus and Acetobacter spp. (dominant microbiota members) found in the gut. In addition, we demonstrated that certain probiotic lactobacilli could ameliorate Duox pathway impairment caused by imidacloprid, but this effect was not directly dependent on the Duox pathway itself. This study is the first to demonstrate the deleterious effects that neonicotinoids can have on Duox-mediated generation of H2O2 and highlights a novel coordination between two important innate immune pathways present in insects.IMPORTANCE Sublethal exposure to certain pesticides (e.g., neonicotinoid insecticides) is suspected to contribute to honey bee (Apis mellifera) population decline in North America. Neonicotinoids are known to interfere with immune pathways in the gut of insects, but the underlying mechanisms remain elusive. We used a Drosophila melanogaster model to understand how imidacloprid (a common neonicotinoid) interferes with two innate immune pathways-Duox and Imd. We found that imidacloprid dysregulates these pathways to reduce hydrogen peroxide production, ultimately leading to a dysbiotic shift in the gut microbiota. Intriguingly, we found that presupplementation with probiotic bacteria could mitigate the harmful effects of imidacloprid. Thus, these observations uncover a novel mechanism of pesticide-induced immunosuppression that exploits the interconnectedness of two important insect immune pathways.}, }
@article {pmid31573550, year = {2019}, author = {Dabke, K and Hendrick, G and Devkota, S}, title = {The gut microbiome and metabolic syndrome.}, journal = {The Journal of clinical investigation}, volume = {129}, number = {10}, pages = {4050-4057}, pmid = {31573550}, issn = {1558-8238}, mesh = {Animals ; Diet ; Dyslipidemias/etiology/microbiology ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/*physiology ; Host Microbial Interactions/physiology ; Humans ; Inflammation/etiology/microbiology ; Insulin Resistance ; Metabolic Syndrome/*etiology/metabolism/microbiology ; Models, Biological ; Obesity/etiology/microbiology ; }, abstract = {The metabolic syndrome (MetS) is a constellation of risk factors that, if left untreated, will often progress to greater metabolic defects such as type 2 diabetes and nonalcoholic fatty liver disease. While these risk factors have been established for over 40 years, the definition of MetS warrants reconsideration in light of the substantial data that have emerged from studies of the gut microbiome. In this Review we present the existing recent literature that supports the gut microbiome's potential influence on the various risk factors of MetS. The interplay of the intestinal microbiota with host metabolism has been shown to be mediated by a myriad of factors, including a defective gut barrier, bile acid metabolism, antibiotic use, and the pleiotropic effects of microbially produced metabolites. These data show that events that start in the gut, often in response to external cues such as diet and circadian disruption, have far-reaching effects beyond the gut.}, }
@article {pmid31572693, year = {2019}, author = {Reid, G}, title = {The Need to Focus on Therapy Instead of Associations.}, journal = {Frontiers in cellular and infection microbiology}, volume = {9}, number = {}, pages = {327}, pmid = {31572693}, issn = {2235-2988}, mesh = {Dysbiosis/microbiology/*therapy ; Female ; Humans ; Metagenomics ; *Microbial Interactions ; *Microbiota ; Probiotics/*administration &amp; dosage ; Sequence Analysis, DNA ; Vagina/*microbiology ; Vaginosis, Bacterial/microbiology/*therapy ; }, abstract = {Molecular analyses of the vaginal microbiota have uncovered a vast array of organisms in this niche, but not so far changed what has been known for a long time: lactobacilli are dominant in health, and the diagnosis and treatment of symptomatic bacterial vaginosis is sub-optimal, and has not changed for over 40 years. While the lowering cost of DNA sequencing has attracted more researchers to the field, and bioinformatics, and statistical tools have made it possible to produce large datasets, it is functional and actionable studies that are more urgently needed, not more microbial abundance, and health or disease-associative data. The triggers of dysbiosis remain to be identified, but ultimately treatment will require disrupting biofilms of primarily anaerobic bacteria and replacing them with the host's own lactobacilli, or health-promoting organisms. The options of using probiotic strains to displace the biofilms and for prebiotics to encourage resurgence of the indigenous lactobacilli hold great promise, but more researchers need to develop, and test these concepts in humans. The enormity of the problem of vaginal dysbiosis cannot be understated. It should not take another 40 years to offer better management options.}, }
@article {pmid31563878, year = {2019}, author = {Cammarota, G and Ianiro, G and Kelly, CR and Mullish, BH and Allegretti, JR and Kassam, Z and Putignani, L and Fischer, M and Keller, JJ and Costello, SP and Sokol, H and Kump, P and Satokari, R and Kahn, SA and Kao, D and Arkkila, P and Kuijper, EJ and Vehreschild, MJG and Pintus, C and Lopetuso, L and Masucci, L and Scaldaferri, F and Terveer, EM and Nieuwdorp, M and López-Sanromán, A and Kupcinskas, J and Hart, A and Tilg, H and Gasbarrini, A}, title = {International consensus conference on stool banking for faecal microbiota transplantation in clinical practice.}, journal = {Gut}, volume = {68}, number = {12}, pages = {2111-2121}, pmid = {31563878}, issn = {1468-3288}, mesh = {Clostridioides difficile/*isolation &amp; purification ; Clostridium Infections/microbiology/*therapy ; *Consensus ; Donor Selection ; Fecal Microbiota Transplantation/*methods ; *Gastrointestinal Microbiome ; Humans ; Specimen Handling/methods ; }, abstract = {Although faecal microbiota transplantation (FMT) has a well-established role in the treatment of recurrent Clostridioides difficile infection (CDI), its widespread dissemination is limited by several obstacles, including lack of dedicated centres, difficulties with donor recruitment and complexities related to regulation and safety monitoring. Given the considerable burden of CDI on global healthcare systems, FMT should be widely available to most centres.Stool banks may guarantee reliable, timely and equitable access to FMT for patients and a traceable workflow that ensures safety and quality of procedures. In this consensus project, FMT experts from Europe, North America and Australia gathered and released statements on the following issues related to the stool banking: general principles, objectives and organisation of the stool bank; selection and screening of donors; collection, preparation and storage of faeces; services and clients; registries, monitoring of outcomes and ethical issues; and the evolving role of FMT in clinical practice,Consensus on each statement was achieved through a Delphi process and then in a plenary face-to-face meeting. For each key issue, the best available evidence was assessed, with the aim of providing guidance for the development of stool banks in order to promote accessibility to FMT in clinical practice.}, }
@article {pmid31562947, year = {2020}, author = {Hynönen, U and Zoetendal, EG and Virtala, AK and Shetty, S and Hasan, S and Jakava-Viljanen, M and de Vos, WM and Palva, A}, title = {Molecular ecology of the yet uncultured bacterial Ct85-cluster in the mammalian gut.}, journal = {Anaerobe}, volume = {62}, number = {}, pages = {102104}, doi = {10.1016/j.anaerobe.2019.102104}, pmid = {31562947}, issn = {1095-8274}, mesh = {Animals ; Cluster Analysis ; Databases, Genetic ; Female ; *Gastrointestinal Microbiome ; High-Throughput Nucleotide Sequencing ; Humans ; Male ; Mammals ; *Metagenome ; *Metagenomics/methods ; Molecular Typing ; Phylogeny ; RNA, Ribosomal, 16S/genetics ; }, abstract = {In our previous studies on irritable bowel syndrome (IBS) -associated microbiota by molecular methods, we demonstrated that a particular 16S rRNA gene amplicon was more abundant in the feces of healthy subjects or mixed type IBS (IBS-M) -sufferers than in the feces of individuals with diarrhea-type IBS (IBS-D). In the current study, we demonstrated that this, so called Ct85-amplicon, consists of a cluster of very heterogeneous 16S rRNA gene sequences, and defined six 16S rRNA gene types, a to f, within this cluster, each representing a novel species-, genus- or family level taxon. We then designed specific PCR primers for these sequence types, mapped the distribution of the Ct85-cluster sequences and that of the newly defined sequence types in several animal species and compared the sequence types present in the feces of healthy individuals and IBS sufferers using two IBS study cohorts, Finnish and Dutch. Various Ct85-cluster sequence types were detected in the fecal samples of several companion and production animal species with remarkably differing prevalences and abundances. The Ct85 sequence type composition of swine closely resembled that of humans. One of the five types (d) shared between humans and swine was not present in any other animals tested, while one sequence type (b) was found only in human samples. In both IBS study cohorts, one type (e) was more prevalent in healthy individuals than in the IBS-M group. By revealing various sequence types in the widespread Ct85-cluster and their distribution, the results improve our understanding of these uncultured bacteria, which is essential for future efforts to cultivate representatives of the Ct85-cluster and reveal their roles in IBS.}, }
@article {pmid31555247, year = {2019}, author = {Ghose, C and Ly, M and Schwanemann, LK and Shin, JH and Atab, K and Barr, JJ and Little, M and Schooley, RT and Chopyk, J and Pride, DT}, title = {The Virome of Cerebrospinal Fluid: Viruses Where We Once Thought There Were None.}, journal = {Frontiers in microbiology}, volume = {10}, number = {}, pages = {2061}, pmid = {31555247}, issn = {1664-302X}, abstract = {Traditionally, medicine has held that some human body sites are sterile and that the introduction of microbes to these sites results in infections. This paradigm shifted significantly with the discovery of the human microbiome and acceptance of these commensal microbes living across the body. However, the central nervous system (CNS) is still believed by many to be sterile in healthy people. Using culture-independent methods, we examined the virome of cerebrospinal fluid (CSF) from a cohort of mostly healthy human subjects. We identified a community of DNA viruses, most of which were identified as bacteriophages. Compared to other human specimen types, CSF viromes were not ecologically distinct. There was a high alpha diversity cluster that included feces, saliva, and urine, and a low alpha diversity cluster that included CSF, body fluids, plasma, and breast milk. The high diversity cluster included specimens known to have many bacteria, while other specimens traditionally assumed to be sterile formed the low diversity cluster. There was an abundance of viruses shared among CSF, breast milk, plasma, and body fluids, while each generally shared less with urine, feces, and saliva. These shared viruses ranged across different virus families, indicating that similarities between these viromes represent more than just a single shared virus family. By identifying a virome in the CSF of mostly healthy individuals, it is now less likely that any human body site is devoid of microbes, which further highlights the need to decipher the role that viral communities may play in human health.}, }
@article {pmid31555238, year = {2019}, author = {Pires, ES and Hardoim, CCP and Miranda, KR and Secco, DA and Lobo, LA and de Carvalho, DP and Han, J and Borchers, CH and Ferreira, RBR and Salles, JF and Domingues, RMCP and Antunes, LCM}, title = {The Gut Microbiome and Metabolome of Two Riparian Communities in the Amazon.}, journal = {Frontiers in microbiology}, volume = {10}, number = {}, pages = {2003}, pmid = {31555238}, issn = {1664-302X}, abstract = {During the last decades it has become increasingly clear that the microbes that live on and in humans are critical for health. The communities they form, termed microbiomes, are involved in fundamental processes such as the maturation and constant regulation of the immune system. Additionally, they constitute a strong defense barrier to invading pathogens, and are also intricately linked to nutrition. The parameters that affect the establishment and maintenance of these microbial communities are diverse, and include the genetic background, mode of birth, nutrition, hygiene, and host lifestyle in general. Here, we describe the characterization of the gut microbiome of individuals living in the Amazon, and the comparison of these microbial communities to those found in individuals from an urban, industrialized setting. Our results showed striking differences in microbial communities from these two types of populations. Additionally, we used high-throughput metabolomics to study the chemical ecology of the gut environment and found significant metabolic changes between the two populations. Although we cannot point out a single cause for the microbial and metabolic changes observed between Amazonian and urban individuals, they are likely to include dietary differences as well as diverse patterns of environmental exposure. To our knowledge, this is the first description of gut microbial and metabolic profiles in Amazonian populations, and it provides a starting point for thorough characterizations of the impact of individual environmental conditions on the human microbiome and metabolome.}, }
@article {pmid31546582, year = {2019}, author = {Dizzell, S and Nazli, A and Reid, G and Kaushic, C}, title = {Protective Effect of Probiotic Bacteria and Estrogen in Preventing HIV-1-Mediated Impairment of Epithelial Barrier Integrity in Female Genital Tract.}, journal = {Cells}, volume = {8}, number = {10}, pages = {}, pmid = {31546582}, issn = {2073-4409}, support = {FRN 126019//CIHR/Canada ; FRN 138657//CIHR/Canada ; }, mesh = {Adult ; Antibiosis/drug effects/physiology ; Cell Membrane Permeability/*drug effects/immunology ; Cells, Cultured ; Cytoprotection/*drug effects/immunology ; Epithelial Cells/*drug effects/metabolism/virology ; Estradiol/*pharmacology ; Female ; Genitalia, Female/*drug effects/metabolism/pathology/virology ; HIV Infections/prevention &amp; control ; HIV-1/drug effects/pathogenicity/*physiology ; Humans ; Immunity, Innate/drug effects/physiology ; Lactobacillus/physiology ; Middle Aged ; Primary Cell Culture ; Probiotics/*pharmacology ; Progesterone/pharmacology ; }, abstract = {Approximately 40% of global HIV-1 transmission occurs in the female genital tract (FGT) through heterosexual transmission. Epithelial cells lining the FGT provide the first barrier to HIV-1 entry. Previous studies have suggested that certain hormonal contraceptives or a dysbiosis of the vaginal microbiota can enhance HIV-1 acquisition in the FGT. We examined the effects of lactobacilli and female sex hormones on the barrier functions and innate immune responses of primary endometrial genital epithelial cells (GECs). Two probiotic strains, Lactobacillus reuteri RC-14 and L. rhamnosus GR-1, were tested, as were sex hormones estrogen (E2), progesterone (P4), and the hormonal contraceptive medroxyprogesterone acetate (MPA). Our results demonstrate that probiotic lactobacilli enhance barrier function without affecting cytokines. Treatment of GECs with MPA resulted in reduced barrier function. In contrast, E2 treatment enhanced barrier function and reduced production of proinflammatory cytokines. Comparison of hormones plus lactobacilli as a pre-treatment prior to HIV exposure revealed a dominant effect of lactobacilli in preventing loss of barrier function by GECs. In summary, the combination of E2 and lactobacilli had the best protective effect against HIV-1 seen by enhancement of barrier function and reduction in proinflammatory cytokines. These studies provide insights into how probiotic lactobacilli in the female genital microenvironment can alter HIV-1-mediated barrier disruption and how the combination of E2 and lactobacilli may decrease susceptibility to primary HIV infection.}, }
@article {pmid31545899, year = {2019}, author = {Chu, J and Vila-Farres, X and Brady, SF}, title = {Bioactive Synthetic-Bioinformatic Natural Product Cyclic Peptides Inspired by Nonribosomal Peptide Synthetase Gene Clusters from the Human Microbiome.}, journal = {Journal of the American Chemical Society}, volume = {141}, number = {40}, pages = {15737-15741}, pmid = {31545899}, issn = {1520-5126}, support = {R35 GM122559/GM/NIGMS NIH HHS/United States ; U19 AI109713/AI/NIAID NIH HHS/United States ; U19 AI142731/AI/NIAID NIH HHS/United States ; }, mesh = {Biological Products/*chemistry ; Biosynthetic Pathways/*genetics ; Computational Biology/methods ; Genome, Bacterial ; Humans ; Microbiota/*genetics ; Molecular Structure ; *Multigene Family ; Peptide Synthases/*genetics ; Peptides, Cyclic/*chemistry ; }, abstract = {Bioinformatic analysis of sequenced bacterial genomes has uncovered an increasing number of natural product biosynthetic gene clusters (BGCs) to which no known bacterial metabolite can be ascribed. One emerging method we have investigated for studying these BGCs is the synthetic-Bioinformatic Natural Product (syn-BNP) approach. The syn-BNP approach replaces transcription, translation, and in vivo enzymatic biosynthesis of natural products with bioinformatic algorithms to predict the output of a BGC and in vitro chemical synthesis to produce the predicted structure. Here we report on expanding the syn-BNP approach to the design and synthesis of cyclic peptides inspired by nonribosomal peptide synthetase BGCs associated with the human microbiota. While no syn-BNPs we tested inhibited the growth of bacteria or yeast, five were found to be active in the human cell-based MTT metabolic activity assay. Interestingly, active peptides were mostly inspired by BGCs found in the genomes of opportunistic pathogens that are often more commonly associated with environments outside the human microbiome. The cyclic syn-BNP studies presented here provide further evidence of its potential for identifying bioactive small molecules directly from the instructions encoded in the primary sequences of natural product BGCs.}, }
@article {pmid31545522, year = {2019}, author = {Bosch, TCG}, title = {Multidisciplinary Approaches to Exploring Human-Microbiome Interactions.}, journal = {BioEssays : news and reviews in molecular, cellular and developmental biology}, volume = {41}, number = {10}, pages = {1-2}, doi = {10.1002/bies.201900130}, pmid = {31545522}, issn = {1521-1878}, mesh = {Humans ; *Microbiota ; }, }
@article {pmid31537666, year = {2019}, author = {Yerushalmy, O and Coppenhagen-Glazer, S and Nir-Paz, R and Tuomala, H and Skurnik, M and Kiljunen, S and Hazan, R}, title = {Complete Genome Sequences of Two Klebsiella pneumoniae Phages Isolated as Part of an International Effort.}, journal = {Microbiology resource announcements}, volume = {8}, number = {38}, pages = {}, pmid = {31537666}, issn = {2576-098X}, abstract = {We report the genomic sequences of phages KpCHEMY26 and KpGranit, isolated in Israel during a worldwide effort against a multidrug- and phage-resistant strain of Klebsiella pneumoniae from a patient in Finland. These results demonstrate the importance of an efficient worldwide network for collaborating in personalized therapy for infectious diseases.}, }
@article {pmid31533707, year = {2019}, author = {Willmann, M and Vehreschild, MJGT and Biehl, LM and Vogel, W and Dörfel, D and Hamprecht, A and Seifert, H and Autenrieth, IB and Peter, S}, title = {Distinct impact of antibiotics on the gut microbiome and resistome: a longitudinal multicenter cohort study.}, journal = {BMC biology}, volume = {17}, number = {1}, pages = {76}, pmid = {31533707}, issn = {1741-7007}, mesh = {Anti-Bacterial Agents/*adverse effects/therapeutic use ; Ciprofloxacin/*adverse effects/therapeutic use ; Cohort Studies ; *Drug Resistance, Microbial/drug effects/genetics ; Gastrointestinal Microbiome/*drug effects ; Genes, Bacterial/drug effects ; Germany ; Humans ; Longitudinal Studies ; Metagenomics/methods ; Plasmids/*drug effects ; Trimethoprim, Sulfamethoxazole Drug Combination/*adverse effects/therapeutic use ; }, abstract = {BACKGROUND: The selection pressure exercised by antibiotic drugs is an important consideration for the wise stewardship of antimicrobial treatment programs. Treatment decisions are currently based on crude assumptions, and there is an urgent need to develop a more quantitative knowledge base that can enable predictions of the impact of individual antibiotics on the human gut microbiome and resistome.<br><br>RESULTS: Using shotgun metagenomics, we quantified changes in the gut microbiome in two cohorts of hematological patients receiving prophylactic antibiotics; one cohort was treated with ciprofloxacin in a hospital in T&#xfc;bingen and the other with cotrimoxazole in a hospital in Cologne. Analyzing this rich longitudinal dataset, we found that gut microbiome diversity was reduced in both treatment cohorts to a similar extent, while effects on the gut resistome differed. We observed a sharp increase in the relative abundance of sulfonamide antibiotic resistance genes (ARGs) by 148.1% per cumulative defined daily dose of cotrimoxazole in the Cologne cohort, but not in the T&#xfc;bingen cohort treated with ciprofloxacin. Through multivariate modeling, we found that factors such as individual baseline microbiome, resistome, and plasmid diversity; liver/kidney function; and concurrent medication, especially virostatic agents, influence resistome alterations. Strikingly, we observed different effects on the plasmidome in the two treatment groups. There was a substantial increase in the abundance of ARG-carrying plasmids in the cohort treated with cotrimoxazole, but not in the cohort treated with ciprofloxacin, indicating that cotrimoxazole might contribute more efficiently to the spread of resistance.<br><br>CONCLUSIONS: Our study represents a step forward in developing the capability to predict the effect of individual antimicrobials on the human microbiome and resistome. Our results indicate that to achieve this, integration of the individual baseline microbiome, resistome, and mobilome status as well as additional individual patient factors will be required. Such personalized predictions may in the future increase patient safety and reduce the spread of resistance.<br><br>TRIAL REGISTRATION: ClinicalTrials.gov, NCT02058888 . Registered February 10 2014.}, }
@article {pmid31532533, year = {2019}, author = {Bhuta, R and Nieder, M and Jubelirer, T and Ladas, EJ}, title = {The Gut Microbiome and Pediatric Cancer: Current Research and Gaps in Knowledge.}, journal = {Journal of the National Cancer Institute. Monographs}, volume = {2019}, number = {54}, pages = {169-173}, doi = {10.1093/jncimonographs/lgz026}, pmid = {31532533}, issn = {1745-6614}, mesh = {Age Factors ; Anti-Infective Agents/adverse effects/therapeutic use ; Child ; Comorbidity ; *Disease Susceptibility ; Dysbiosis ; *Gastrointestinal Microbiome/drug effects/immunology ; Humans ; Immunomodulation ; Microbiota ; Neoplasms/diagnosis/*epidemiology/*etiology/therapy ; Prognosis ; }, abstract = {The human microbiome consists of trillions of microbial cells that interact with one another and the human host to play a clinically significant role in health and disease. Gut microbial changes have been identified in cancer pathogenesis, at disease diagnosis, during therapy, and even long after completion of treatment. Alterations in the gut microbiome have been linked to treatment-related toxicity and potential long-term morbidity and mortality in children with cancer. Such alterations are plausible given immune modulation due to disease as well as exposure to cytotoxic chemotherapy, infections, and antibiotics. The following review presents our current scientific understanding on the role of the gut microbiome in pediatric cancer, identifies gaps in knowledge, and suggests future research goals.}, }
@article {pmid31530872, year = {2019}, author = {Köberl, M and Erschen, S and Etemadi, M and White, RA and El-Arabi, TF and Berg, G}, title = {Deciphering the microbiome shift during fermentation of medicinal plants.}, journal = {Scientific reports}, volume = {9}, number = {1}, pages = {13461}, pmid = {31530872}, issn = {2045-2322}, support = {J 3638/FWF_/Austrian Science Fund FWF/Austria ; T 847/FWF_/Austrian Science Fund FWF/Austria ; }, mesh = {Brassica/microbiology ; Calendula/*microbiology ; Fermentation ; Fermented Foods ; Lactobacillales/physiology ; Matricaria/*microbiology ; Microbiota/genetics/*physiology ; Plant Leaves/microbiology ; Plants, Medicinal/*microbiology ; RNA, Ribosomal, 16S ; }, abstract = {The importance of the human-microbiome relationship for positive health outcomes has become more apparent over the last decade. Influencing the gut microbiome via modification of diet represents a possibility of maintaining a healthy gut flora. Fermented food and lactic acid bacteria (LAB) display a preventive way to inhibit microbial dysbioses and diseases, but their ecology on plants is poorly understood. We characterized the microbiome of medicinal plants (Matricaria chamomilla L. and Calendula officinalis L.) using 16S rRNA gene profiling from leaves that were fermented over a six-week time course. The unfermented samples were characterized by a distinct phyllosphere microbiome, while the endosphere revealed a high similarity. During fermentation, significant microbial shifts were observed, whereby LAB were enhanced in all approaches but never numerically dominated. Among the LAB, Enterococcaceae were identified as the most dominant family in both plants. M. chamomilla community had higher relative abundances of Lactobacillaceae and Carnobacteriaceae, while C. officinalis showed a higher presence of Leuconostocaceae and Streptococcaceae. The natural leaf microbiome and the indigenous LAB communities of field-grown Asteraceae medicinal plants are plant-specific and habitat-specific and are subjected to significant shifts during fermentation. Leaf surfaces as well as leaf endospheres were identified as sources for biopreservative LAB.}, }
@article {pmid31524305, year = {2019}, author = {Amato, KR and Jeyakumar, T and Poinar, H and Gros, P}, title = {Shifting Climates, Foods, and Diseases: The Human Microbiome through Evolution.}, journal = {BioEssays : news and reviews in molecular, cellular and developmental biology}, volume = {41}, number = {10}, pages = {e1900034}, doi = {10.1002/bies.201900034}, pmid = {31524305}, issn = {1521-1878}, mesh = {*Biological Evolution ; Climate ; Communicable Diseases ; Diet ; *Gastrointestinal Microbiome ; *Host Microbial Interactions ; Humans ; }, abstract = {Human evolution has been punctuated by climate anomalies, structuring environments, deadly infections, and altering landscapes. How well humans adapted to these new circumstances had direct effects on fitness and survival. Here, how the gut microbiome could have contributed to human evolutionary success through contributions to host nutritional buffering and infectious disease resistance is reviewed. How changes in human genetics, diet, disease exposure, and social environments almost certainly altered microbial community composition is also explored. Emerging research points to the microbiome as a key player in host responses to environmental change. Therefore, the reciprocal interactions between humans and their microbes are likely to have shaped human patterns of local adaptation throughout our shared evolutionary history. Recent alterations in human lifestyle, however, are altering human microbiomes in unprecedented ways. The consequences of interrupted host-microbe relationships for human adaptive potential in the future are unknown.}, }
@article {pmid31522775, year = {2021}, author = {Requena, T and Velasco, M}, title = {The human microbiome in sickness and in health.}, journal = {Revista clinica espanola}, volume = {221}, number = {4}, pages = {233-240}, doi = {10.1016/j.rce.2019.07.004}, pmid = {31522775}, issn = {1578-1860}, abstract = {The study of the human microbiome has led to an exceptional increase in the current understanding of the importance of microbiota for health throughout all stages of life. Human microbial colonization occurs in the skin, genitourinary system and, mainly, in the oral cavity and intestinal tract. In these locations, the human microbiota establishes a symbiotic relationship with the host and helps maintain the physiological homeostasis. Lifestyle, age, diet and use of antibiotics are the main regulators of the composition and functionality of human microbiota. Recent studies have indicated the reduction in microbial diversity as one of the contributors to the development of diseases. In addition to phylogenetic diversity studies, further metagenomic studies are needed at the functional level of the human microbiome to improve our understanding of its involvement in human health.}, }
@article {pmid31520544, year = {2020}, author = {Polkowska-Pruszyńska, B and Gerkowicz, A and Krasowska, D}, title = {The gut microbiome alterations in allergic and inflammatory skin diseases - an update.}, journal = {Journal of the European Academy of Dermatology and Venereology : JEADV}, volume = {34}, number = {3}, pages = {455-464}, doi = {10.1111/jdv.15951}, pmid = {31520544}, issn = {1468-3083}, mesh = {Acne Vulgaris/epidemiology ; Dermatitis/*etiology ; Dysbiosis/*complications ; *Gastrointestinal Microbiome ; Humans ; Hypersensitivity/*etiology ; Psoriasis/etiology ; }, abstract = {The human microbiome is a wide range of microorganisms residing in and on our body. The homeostasis between host immune system and the microbial environment allows mutual benefits and protection. Physiological bacterial colonization is essential for the establishment of organism immunity. The human microbiota ecosystem can be divided into several compartments, out of which intestinal flora strongly affects our health and plays a crucial role in the pathophysiology of many diseases. The gastrointestinal tract, being a major guardian of the immune system, maintains the homeostasis with the commensal microorganisms by tolerating the typical flora antigens. The dysbiosis may trigger an inflammatory response followed by tissue damage or autoimmune processes. The gut microbiome alterations are linked to the pathogenesis of the allergic, cardiovascular, gastrointestinal, metabolic, neurodevelopmental, psychiatric and neurodegenerative diseases and cancer. Moreover, there is increasing evidence connecting the skin condition with the gastrointestinal microbiome, which has been described as the skin-gut axis. The aim of this study was to review the literature regarding the role of the gut microbiome alterations in the pathogenesis of selected allergic and inflammatory skin diseases.}, }
@article {pmid31519129, year = {2019}, author = {Ndika, J and Seemab, U and Poon, WL and Fortino, V and El-Nezami, H and Karisola, P and Alenius, H}, title = {Silver, titanium dioxide, and zinc oxide nanoparticles trigger miRNA/isomiR expression changes in THP-1 cells that are proportional to their health hazard potential.}, journal = {Nanotoxicology}, volume = {13}, number = {10}, pages = {1380-1395}, doi = {10.1080/17435390.2019.1661040}, pmid = {31519129}, issn = {1743-5404}, mesh = {Gene Expression Profiling ; Gene Expression Regulation/drug effects ; Humans ; Metal Nanoparticles/*toxicity ; MicroRNAs/drug effects/genetics/*metabolism ; Particle Size ; RNA, Messenger ; Silver/*toxicity ; THP-1 Cells ; Titanium/*toxicity ; Zinc Oxide/*toxicity ; }, abstract = {After over a decade of nanosafety research, it is indisputable that the vast majority of nano-sized particles induce a plethora of adverse cellular responses - the severity of which is linked to the material's physicochemical properties. Differentiated THP-1 cells were previously exposed for 6 h and 24 h to silver, titanium dioxide, and zinc oxide nanoparticles at the maximum molar concentration at which no more than 15% cellular cytotoxicity was observed. All three nanoparticles differed in extent of induction of biological pathways corresponding to immune response signaling and metal ion homeostasis. In this study, we integrated gene and miRNA expression profiles from the same cells to propose miRNA biomarkers of adverse exposure to metal-based nanoparticles. We employed RNA sequencing together with a quantitative strategy that also enables analysis of the overlooked repertoire of length and sequence miRNA variants called isomiRs. Whilst only modest changes in expression were observed within the first 6 h of exposure, the miRNA/isomiR (miR) profiles of each nanoparticle were unique. Via canonical correlation and pathway enrichment analyses, we identified a co-regulated miR-mRNA cluster, predicted to be highly relevant for cellular response to metal ion homeostasis. These miRs were annotated to be canonical or variant isoforms of hsa-miR-142-5p, -342-3p, -5100, -6087, -6894-3p, and -7704. Hsa-miR-5100 was differentially expressed in response to each nanoparticle in both the 6 h and 24 h exposures. Taken together, this co-regulated miR-mRNA cluster could represent potential biomarkers of sub-toxic metal-based nanoparticle exposure.}, }
@article {pmid31502535, year = {2019}, author = {Forsberg, KJ and Bhatt, IV and Schmidtke, DT and Javanmardi, K and Dillard, KE and Stoddard, BL and Finkelstein, IJ and Kaiser, BK and Malik, HS}, title = {Functional metagenomics-guided discovery of potent Cas9 inhibitors in the human microbiome.}, journal = {eLife}, volume = {8}, number = {}, pages = {}, pmid = {31502535}, issn = {2050-084X}, support = {F31 GM125201/GM/NIGMS NIH HHS/United States ; R01 GM105691/GM/NIGMS NIH HHS/United States ; R01 GM124141/GM/NIGMS NIH HHS/United States ; R01 GM124131/GM/NIGMS NIH HHS/United States ; }, mesh = {Bacterial Proteins/genetics/isolation &amp; purification/*metabolism ; CRISPR-Associated Protein 9/*antagonists &amp; inhibitors ; Enzyme Inhibitors/isolation &amp; purification/*metabolism ; Feces/microbiology/virology ; Humans ; Metagenomics ; *Microbiota ; Mouth/microbiology/virology ; Viral Proteins/genetics/isolation &amp; purification/*metabolism ; }, abstract = {CRISPR-Cas systems protect bacteria and archaea from phages and other mobile genetic elements, which use small anti-CRISPR (Acr) proteins to overcome CRISPR-Cas immunity. Because Acrs are challenging to identify, their natural diversity and impact on microbial ecosystems are underappreciated. To overcome this discovery bottleneck, we developed a high-throughput functional selection to isolate ten DNA fragments from human oral and fecal metagenomes that inhibit Streptococcus pyogenes Cas9 (SpyCas9) in Escherichia coli. The most potent Acr from this set, AcrIIA11, was recovered from a Lachnospiraceae phage. We found that AcrIIA11 inhibits SpyCas9 in bacteria and in human cells. AcrIIA11 homologs are distributed across diverse bacteria; many distantly-related homologs inhibit both SpyCas9 and a divergent Cas9 from Treponema denticola. We find that AcrIIA11 antagonizes SpyCas9 using a different mechanism than other previously characterized Type II-A Acrs. Our study highlights the power of functional selection to uncover widespread Cas9 inhibitors within diverse microbiomes.}, }
@article {pmid31502171, year = {2020}, author = {Kumar, M and Singh, P and Murugesan, S and Vetizou, M and McCulloch, J and Badger, JH and Trinchieri, G and Al Khodor, S}, title = {Microbiome as an Immunological Modifier.}, journal = {Methods in molecular biology (Clifton, N.J.)}, volume = {2055}, number = {}, pages = {595-638}, pmid = {31502171}, issn = {1940-6029}, support = {ZIA BC011153/ImNIH/Intramural NIH HHS/United States ; }, mesh = {Age Factors ; Aged ; Bacteria/*classification/genetics/isolation &amp; purification ; Bacterial Proteins/*genetics ; Gene Expression Profiling ; Gene Expression Regulation, Bacterial ; High-Throughput Nucleotide Sequencing ; Humans ; Metagenomics/*methods ; Microbiota ; Middle Aged ; Sequence Analysis, DNA ; }, abstract = {Humans are living ecosystems composed of human cells and microbes. The microbiome is the collection of microbes (microbiota) and their genes. Recent breakthroughs in the high-throughput sequencing technologies have made it possible for us to understand the composition of the human microbiome. Launched by the National Institutes of Health in USA, the human microbiome project indicated that our bodies harbor a wide array of microbes, specific to each body site with interpersonal and intrapersonal variabilities. Numerous studies have indicated that several factors influence the development of the microbiome including genetics, diet, use of antibiotics, and lifestyle, among others. The microbiome and its mediators are in a continuous cross talk with the host immune system; hence, any imbalance on one side is reflected on the other. Dysbiosis (microbiota imbalance) was shown in many diseases and pathological conditions such as inflammatory bowel disease, celiac disease, multiple sclerosis, rheumatoid arthritis, asthma, diabetes, and cancer. The microbial composition mirrors inflammation variations in certain disease conditions, within various stages of the same disease; hence, it has the potential to be used as a biomarker.}, }
@article {pmid31495055, year = {2019}, author = {Boto, L and Pineda, M and Pineda, R}, title = {Potential impacts of horizontal gene transfer on human health and physiology and how anthropogenic activity can affect it.}, journal = {The FEBS journal}, volume = {286}, number = {20}, pages = {3959-3967}, doi = {10.1111/febs.15054}, pmid = {31495055}, issn = {1742-4658}, support = {CGL2016-75262-P//Direcci&#xf3;n General de Investigaci&#xf3;n Cient&#xed;fica y T&#xe9;cnica/International ; }, mesh = {Bacteria/*genetics ; Bacterial Proteins/*genetics ; Biodiversity ; Gene Transfer, Horizontal/*genetics ; *Genome, Bacterial ; Humans ; Microbiota/*physiology ; }, abstract = {Horizontal gene transfer (HGT) is widespread among prokaryotes driving their evolution. In this paper, we review the potential impact in humans of the HGT between prokaryotes living in close association with humans in two scenarios: horizontal transfer in human microbiomes and transfer between microbes living in human managed environments. Although our vision is focused on the possible impact of these transfers in the propagation of antibiotic resistance genes or pathogenicity determinants, we also discuss possible human physiological adaptations via gene transfer between resident and occasional bacteria in the human microbiome.}, }
@article {pmid31493521, year = {2019}, author = {Fielding, RA and Reeves, AR and Jasuja, R and Liu, C and Barrett, BB and Lustgarten, MS}, title = {Muscle strength is increased in mice that are colonized with microbiota from high-functioning older adults.}, journal = {Experimental gerontology}, volume = {127}, number = {}, pages = {110722}, pmid = {31493521}, issn = {1873-6815}, support = {K01 AG050700/AG/NIA NIH HHS/United States ; K23 AG057813/AG/NIA NIH HHS/United States ; P30 AG031679/AG/NIA NIH HHS/United States ; }, mesh = {Aged ; Aged, 80 and over ; Animals ; Bacteroidetes/isolation &amp; purification/physiology ; Body Composition/physiology ; Exercise/*physiology ; Fecal Microbiota Transplantation/methods ; Feces/microbiology ; Female ; Gastrointestinal Microbiome/*physiology ; Humans ; Male ; Muscle Strength/*physiology ; Muscle, Skeletal/physiology ; Prevotella/isolation &amp; purification/physiology ; Sarcopenia/physiopathology ; }, abstract = {Evidence in support of a gut-muscle axis has been reported in rodents, but studies in older adult humans are limited. Accordingly, the primary goals of the present study were to compare gut microbiome composition in older adults that differed in terms of the percentage of whole body lean mass and physical functioning (high-functioning, HF, n = 18; low-functioning, LF, n = 11), and to evaluate the causative role of the gut microbiome on these variables by transferring fecal samples from older adults into germ-free mice. Family-level Prevotellaceae, genus-level Prevotella and Barnesiella, and the bacterial species Barnesiella intestinihominis were higher in HF older adults at the initial study visit, at a 1-month follow-up visit, in HF human fecal donors, and in HF-colonized mice, when compared with their LF counterparts. Grip strength was significantly increased by 6.4% in HF-, when compared with LF-colonized mice. In contrast, despite significant differences for the percentage of whole body lean mass and physical functioning when comparing the human fecal donors, the percentage of whole body lean mass and treadmill endurance capacity were not different when comparing human microbiome-containing mice. In sum, these data suggest a role for gut bacteria on the maintenance of muscle strength, but argue against a role for gut bacteria on the maintenance of the percentage of whole body lean mass or endurance capacity, findings that collectively add to elucidation of the gut-muscle axis in older adults.}, }
@article {pmid31493090, year = {2019}, author = {Wheeler, KM and Liss, MA}, title = {The Microbiome and Prostate Cancer Risk.}, journal = {Current urology reports}, volume = {20}, number = {10}, pages = {66}, pmid = {31493090}, issn = {1534-6285}, mesh = {Animals ; Gastrointestinal Microbiome/physiology ; Humans ; Male ; Mice ; Microbiota/*physiology ; Prostate/*microbiology/virology ; Prostatic Neoplasms/etiology/*microbiology/*therapy/virology ; Urine/microbiology/virology ; Urogenital System/microbiology ; }, abstract = {There is an abundance of evidence that the human microbiome plays an important and nuanced role in controlling human metabolism, immunity, and cancer. Herein we aim to review the most current research looking at prostate cancer and its link with the gut and genitourinary microbiome. There is now a host of evidence for a unique genitourinary (GU) microbiome. The prostate microbiota, to include viral, bacterial, fungal, and parasitic contributions, as assessed from formalin-fixed tissue is described nicely in the study by Banerjee et al. Further hierarchical analysis by this group found a unique microbiome signature for higher Gleason score cancers and validation PCR studies noted a marked number of viral genomic insertions into host DNA. Shretha et al. also recently established unique GU microbiomes in patients with prostate cancer or benign prostate pathology based on urine samples. The gut microbiome likely also has an indirect but significant role in prostate cancer development and treatment. Liss et al. and Golombos et al. found significant associations between specific gut microbiota and prostate cancer. Interestingly, the balance of inflammatory and anti-inflammatory bacterial lipopolysaccharides, production of bile salts, and metabolism of dietary fiber to short chain fatty acids all likely play important roles in creating systemic pro- or anti-carcinogenic states. In terms of prostate cancer treatment effects, Sfanos et al. noted a unique microbial signature in patients undergoing oral androgen deprivation therapy (ADT) as compared with prostate cancer patients not on ADT. Patients undergoing ADT also had enrichment of bacterial metabolic pathways promoting androgen synthesis. Together, these studies have identified a unique GU microbiome and linked both the GU microbiome and unique gut microbial signatures with prostate cancer and prostate cancer treatments. Whether this information can be used in cancer prevention, treatment, or diagnosis are areas of ongoing and active research.}, }
@article {pmid31492655, year = {2019}, author = {Soto-Perez, P and Bisanz, JE and Berry, JD and Lam, KN and Bondy-Denomy, J and Turnbaugh, PJ}, title = {CRISPR-Cas System of a Prevalent Human Gut Bacterium Reveals Hyper-targeting against Phages in a Human Virome Catalog.}, journal = {Cell host &amp; microbe}, volume = {26}, number = {3}, pages = {325-335.e5}, pmid = {31492655}, issn = {1934-6069}, support = {DP5 OD021344/OD/NIH HHS/United States ; R01 HL122593/HL/NHLBI NIH HHS/United States ; }, mesh = {Actinobacteria/virology ; Bacteria/genetics/*virology ; Bacteriophages/*genetics ; Base Sequence ; *CRISPR-Cas Systems ; DNA, Bacterial/analysis ; DNA, Viral/analysis ; Databases, Genetic ; Gastrointestinal Tract/*microbiology ; Genome, Bacterial ; Genome, Viral ; Humans ; Metagenomics ; Microbiota/genetics ; Sequence Analysis, DNA ; }, abstract = {Bacteriophages are abundant within the human gastrointestinal tract, yet their interactions with gut bacteria remain poorly understood, particularly with respect to CRISPR-Cas immunity. Here, we show that the type I-C CRISPR-Cas system in the prevalent gut Actinobacterium Eggerthella lenta is transcribed and sufficient for specific targeting of foreign and chromosomal DNA. Comparative analyses of E. lenta CRISPR-Cas systems across (meta)genomes revealed 2 distinct clades according to cas sequence similarity and spacer content. We assembled a human virome database (HuVirDB), encompassing 1,831 samples enriched for viral DNA, to identify protospacers. This revealed matches for a majority of spacers, a marked increase over other databases, and uncovered "hyper-targeted" phage sequences containing multiple protospacers targeted by several E. lenta strains. Finally, we determined the positional mismatch tolerance of observed spacer-protospacer pairs. This work emphasizes the utility of merging computational and experimental approaches for determining the function and targets of CRISPR-Cas systems.}, }
@article {pmid31492538, year = {2020}, author = {Wang, S and Ryan, CA and Boyaval, P and Dempsey, EM and Ross, RP and Stanton, C}, title = {Maternal Vertical Transmission Affecting Early-life Microbiota Development.}, journal = {Trends in microbiology}, volume = {28}, number = {1}, pages = {28-45}, doi = {10.1016/j.tim.2019.07.010}, pmid = {31492538}, issn = {1878-4380}, mesh = {Adult ; Diet ; Female ; Gastrointestinal Microbiome ; Humans ; Infant ; *Infectious Disease Transmission, Vertical ; Microbiota/*physiology ; Milk, Human/microbiology ; Mothers ; Mycobiome ; Pregnancy ; Probiotics ; Vagina ; }, abstract = {The association of the human microbiome with health outcomes has attracted much interest toward its therapeutic manipulation. The likelihood of modulating the human microbiome in early life is high and offers great potential to exert profound effects on human development since the early microbiota shows more flexibility compared to that of adults. The human microbiota, being similar to human genetics, can be transmitted from mother to infant, providing insights into early microbiota acquisition, subsequent development, and potential opportunities for intervention. Here, we review adaptations of the maternal microbiota during pregnancy, birth, and infancy, the acquisition and succession of early-life microbiota, and highlight recent efforts to elucidate mother-to-infant microbiota transmission. We further discuss how the mother-to-infant microbial transmission is shaped; and finally we address potential directions for future studies to promote our understanding within this field.}, }
@article {pmid31489307, year = {2019}, author = {Cammarota, G and Putignani, L and Gasbarrini, A}, title = {Gut microbiome beats two to zero host genome.}, journal = {Hepatobiliary surgery and nutrition}, volume = {8}, number = {4}, pages = {378-380}, pmid = {31489307}, issn = {2304-3881}, }
@article {pmid31488215, year = {2019}, author = {Badal, VD and Wright, D and Katsis, Y and Kim, HC and Swafford, AD and Knight, R and Hsu, CN}, title = {Challenges in the construction of knowledge bases for human microbiome-disease associations.}, journal = {Microbiome}, volume = {7}, number = {1}, pages = {129}, pmid = {31488215}, issn = {2049-2618}, mesh = {*Data Mining ; Humans ; *Knowledge Bases ; *Microbiota ; *Natural Language Processing ; }, abstract = {The last few years have seen tremendous growth in human microbiome research, with a particular focus on the links to both mental and physical health and disease. Medical and experimental settings provide initial sources of information about these links, but individual studies produce disconnected pieces of knowledge bounded in context by the perspective of expert researchers reading full-text publications. Building a knowledge base (KB) consolidating these disconnected pieces is an essential first step to democratize and accelerate the process of accessing the collective discoveries of human disease connections to the human microbiome. In this article, we survey the existing tools and development efforts that have been produced to capture portions of the information needed to construct a KB of all known human microbiome-disease associations and highlight the need for additional innovations in natural language processing (NLP), text mining, taxonomic representations, and field-wide vocabulary standardization in human microbiome research. Addressing these challenges will enable the construction of KBs that help identify new insights amenable to experimental validation and potentially clinical decision support.}, }
@article {pmid31481604, year = {2019}, author = {Basu Thakur, P and Long, AR and Nelson, BJ and Kumar, R and Rosenberg, AF and Gray, MJ}, title = {Complex Responses to Hydrogen Peroxide and Hypochlorous Acid by the Probiotic Bacterium Lactobacillus reuteri.}, journal = {mSystems}, volume = {4}, number = {5}, pages = {}, pmid = {31481604}, issn = {2379-5077}, support = {R35 GM124590/GM/NIGMS NIH HHS/United States ; }, abstract = {Inflammatory diseases of the gut are associated with increased intestinal oxygen concentrations and high levels of inflammatory oxidants, including hydrogen peroxide (H2O2) and hypochlorous acid (HOCl), which are antimicrobial compounds produced by the innate immune system. This contributes to dysbiotic changes in the gut microbiome, including increased populations of proinflammatory enterobacteria (Escherichia coli and related species) and decreased levels of health-associated anaerobic Firmicutes and Bacteroidetes The pathways for H2O2 and HOCl resistance in E. coli have been well studied, but little is known about how commensal and probiotic bacteria respond to inflammatory oxidants. In this work, we have characterized the transcriptomic response of the anti-inflammatory, gut-colonizing Gram-positive probiotic Lactobacillus reuteri to both H2O2 and HOCl. L. reuteri mounts distinct but overlapping responses to each of these stressors, and both gene expression and survival were strongly affected by the presence or absence of oxygen. Oxidative stress response in L. reuteri required several factors not found in enterobacteria, including the small heat shock protein Lo18, polyphosphate kinase 2, and RsiR, an L. reuteri-specific regulator of anti-inflammatory mechanisms.IMPORTANCE Reactive oxidants, including hydrogen peroxide and hypochlorous acid, are antimicrobial compounds produced by the immune system during inflammation. Little is known, however, about how many important types of bacteria present in the human microbiome respond to these oxidants, especially commensal and other health-associated species. We have now mapped the stress response to both H2O2 and HOCl in the intestinal lactic acid bacterium Lactobacillus reuteri.}, }
@article {pmid31478123, year = {2019}, author = {Abid, MB and Koh, CJ}, title = {Probiotics in health and disease: fooling Mother Nature?.}, journal = {Infection}, volume = {47}, number = {6}, pages = {911-917}, pmid = {31478123}, issn = {1439-0973}, mesh = {Gastrointestinal Microbiome ; Humans ; Observational Studies as Topic ; Probiotics/*therapeutic use ; Randomized Controlled Trials as Topic ; *Terminology as Topic ; }, abstract = {Probiotics are ubiquitous, consumption by the general public is common, and the dogma remains that they are beneficial for general and gut health. However, evolving evidence suggests a potentially "harmful" impact of many commercially available probiotics. There is also significant variability in formulations that leads to a lack of a universally acceptable definition of probiotics. In this perspective, we review the flaws with definition, relevant observational and randomized studies that showed both positive and negative impacts on health and disease, unbiased interpretation of key trials, emerging evidence from microbiome and immuno-oncological studies, and impact on systemic immunity. We propose that caution be exercised prior to endorsements of their illness-directed consumption and rampant general usage. As a deeper understanding of the human microbiome accrues and our ability to manipulate this complex ecosystem improves, the probiotic of tomorrow might be the precision tool that deals with diseases on a broad front. Gut microbiome, akin to fingerprints, is indigenous to an individual and 'one size fits all' prescription strategy should be discouraged until a more universally acceptable 'favorable taxa' or a 'personalized probiotic,' to complement an individual's native microbiota, gets fashioned.}, }
@article {pmid31475212, year = {2019}, author = {Godoy-Vitorino, F}, title = {Human microbial ecology and the rising new medicine.}, journal = {Annals of translational medicine}, volume = {7}, number = {14}, pages = {342}, pmid = {31475212}, issn = {2305-5839}, abstract = {The first life forms on earth were Prokaryotic, and the evolution of all Eukaryotic life occurred with the help of bacteria. Animal-associated microbiota also includes members of the archaea, fungi, protists, and viruses. The genomes of this host-associated microbial life are called the microbiome. Across the mammalian tree, microbiomes guarantee the development of immunity, physiology, and resistance to pathogens. In humans, all surfaces and cavities are colonized by a microbiome, maintained by a careful balance between the host response and its colonizers-thus humans are considered now supraorganisms. These microbiomes supply essential ecosystem services that benefit health through homeostasis, and the loss of the indigenous microbiota leads to dysbiosis, which can have significant consequences to disease. This educational review aims to describe the importance of human microbial ecology, explain the ecological terms applied to the study of the human microbiome, developments within the cutting-edge microbiome field, and implications to diagnostic and treatment.}, }
@article {pmid31474424, year = {2019}, author = {Derrien, M and Alvarez, AS and de Vos, WM}, title = {The Gut Microbiota in the First Decade of Life.}, journal = {Trends in microbiology}, volume = {27}, number = {12}, pages = {997-1010}, doi = {10.1016/j.tim.2019.08.001}, pmid = {31474424}, issn = {1878-4380}, mesh = {Child ; Child, Preschool ; *Diet ; *Gastrointestinal Microbiome ; Humans ; RNA, Ribosomal, 16S/genetics ; Symbiosis ; }, abstract = {Appreciation of the importance of the gut microbiome is growing, and it is becoming increasingly relevant to identify preventive or therapeutic solutions targeting it. The composition and function of the gut microbiota are relatively well described for infants (less than 3 years) and adults, but have been largely overlooked in pre-school (3-6 years) and primary school-age (6-12 years) children, as well as teenagers (12-18 years). Early reports suggested that the infant microbiota would attain an adult-like structure at the age of 3 years, but recent studies have suggested that microbiota development may take longer. This development time is of key importance because there is evidence to suggest that deviations in this development may have consequences in later life. In this review, we provide an overview of current knowledge concerning the gut microbiota, its evolution, variation, and response to dietary challenges during the first decade of life with a focus on healthy pre-school and primary school-age children (up to 12 years) from various populations around the globe. This knowledge should facilitate the identification of diet-based approaches targeting individuals of this age group, to promote the development of a healthy microbiota in later life.}, }
@article {pmid31473416, year = {2019}, author = {Yan, ZZ and Chen, QL and Zhang, YJ and He, JZ and Hu, HW}, title = {Antibiotic resistance in urban green spaces mirrors the pattern of industrial distribution.}, journal = {Environment international}, volume = {132}, number = {}, pages = {105106}, doi = {10.1016/j.envint.2019.105106}, pmid = {31473416}, issn = {1873-6750}, mesh = {Australia ; Cities ; Drug Resistance, Microbial/*genetics ; Environmental Monitoring ; *Genes, Bacterial ; Industry ; *Parks, Recreational ; *Poaceae ; Real-Time Polymerase Chain Reaction ; Soil/*chemistry ; Soil Microbiology ; }, abstract = {Urban green spaces are closely related to the activities and health of urban residents. Turf grass and soil are two major interfaces between the environmental and human microbiome, which represent potential pathways for the spread of antibiotic resistance genes (ARGs) from environmental to human microbiome through skin-surface contact. However, the information regarding the prevalence of ARGs in urban green spaces and drivers in shaping their distribution patterns remain unclear. Here, we profiled a wide spectrum of ARGs in grass phyllosphere and soils from 40 urban parks across Greater Melbourne, Australia, using high throughput quantitative PCR. A total of 217 and 218 unique ARGs and MGEs were detected in grass phyllosphere and soils, respectively, conferring resistance to almost all major classes of antibiotics commonly used in human and animals. The plant microbiome contained a core resistome, which occupied >84% of the total abundance of ARGs. In contrast, no core resistome was identified in the soil microbiome. The difference between plant and soil resistome composition was attributed to the difference in bacterial community structure and intensity of environmental and anthropogenic influence. Most importantly, the abundance of ARGs in urban green spaces was significantly positively related to industrial factors including total number of business, number of manufacturing, and number of electricity, gas, water and waste services in the region. Structural equation models further revealed that industrial distribution was a major factor shaping the ARG profiles in urban green spaces after accounting for multiple drivers. These findings have important implications for mitigation of the potential risks posed by ARGs to urban residents.}, }
@article {pmid31464810, year = {2019}, author = {Putignani, L and Gasbarrini, A and Dallapiccola, B}, title = {Potential of multiomics technology in precision medicine.}, journal = {Current opinion in gastroenterology}, volume = {35}, number = {6}, pages = {491-498}, pmid = {31464810}, issn = {1531-7056}, mesh = {Clinical Decision-Making ; Female ; Forecasting ; Gastrointestinal Microbiome/*genetics/*immunology ; Humans ; Male ; *Patient Selection ; Precision Medicine/*methods/trends ; Role ; }, abstract = {PURPOSE OF REVIEW: The 'precision medicine' refers to the generation of identification and classification criteria for advanced taxonomy of patients, exploiting advanced models to infer optimized clinical decisions for each disease phenotype.<br><br>RECENT FINDINGS: The current article reviews new advances in the past 18 months on the microbiomics science intended as new discipline contributing to advanced 'precision medicine'. Recently published data highlight the importance of multidimensional data in the description of deep disease phenotypes, including microbiome and immune profiling, and support the efficacy of the systems medicine to better stratify patients, hence optimizing diagnostics, clinical management and response to treatments.<br><br>SUMMARY: The articles referenced in this review help inform the reader on new decision-support systems that can be based on multiomics patients' data including microbiome and immune profiling. These harmonized and integrated data can be elaborated by artificial intelligence to generate optimized diagnostic pipelines and clinical interventions.}, }
@article {pmid31457107, year = {2018}, author = {Herd, P and Palloni, A and Rey, F and Dowd, JB}, title = {Social and population health science approaches to understand the human microbiome.}, journal = {Nature human behaviour}, volume = {2}, number = {11}, pages = {808-815}, pmid = {31457107}, issn = {2397-3374}, support = {R01 AG041868/AG/NIA NIH HHS/United States ; UL1 TR000427/TR/NCATS NIH HHS/United States ; P30 AG017266/AG/NIA NIH HHS/United States ; UL1 TR002373/TR/NCATS NIH HHS/United States ; R21 AI121784/AI/NIAID NIH HHS/United States ; }, mesh = {Humans ; *Interdisciplinary Communication ; Interdisciplinary Research/organization &amp; administration/trends ; *Microbiota ; Public Health/methods/trends ; Social Medicine/*methods ; }, abstract = {The microbiome is now considered our 'second genome' with potentially comparable importance to the genome in determining human health. There is, however, a relatively limited understanding of the broader environmental factors, particularly social conditions, that shape variation in human microbial communities. Fulfilling the promise of microbiome research - particularly the microbiome's potential for modification - will require collaboration between biologists and social and population scientists. For life scientists, the plasticity and adaptiveness of the microbiome calls for an agenda to understand the sensitivity of the microbiome to broader social environments already known to be powerful predictors of morbidity and mortality. For social and population scientists, attention to the microbiome may help answer nagging questions about the underlying biological mechanisms that link social conditions to health. We outline key substantive and methodological advances that can be made if collaborations between social and population health scientists and life scientists are strategically pursued.}, }
@article {pmid31456069, year = {2019}, author = {Chen, J and Douglass, J and Prasath, V and Neace, M and Atrchian, S and Manjili, MH and Shokouhi, S and Habibi, M}, title = {The microbiome and breast cancer: a review.}, journal = {Breast cancer research and treatment}, volume = {178}, number = {3}, pages = {493-496}, doi = {10.1007/s10549-019-05407-5}, pmid = {31456069}, issn = {1573-7217}, mesh = {Bacteria/classification/isolation &amp; purification ; Breast/*microbiology/pathology ; Breast Diseases/immunology/microbiology/pathology/therapy ; Breast Neoplasms/immunology/*microbiology/pathology/therapy ; Dysbiosis/microbiology ; Female ; Gastrointestinal Microbiome ; Humans ; *Microbiota ; Skin/microbiology ; }, abstract = {The human microbiome plays an integral role in physiology, with most microbes considered benign or beneficial. However, some microbes are known to be detrimental to human health, including organisms linked to cancers and other diseases characterized by aberrant inflammation. Dysbiosis, a state of microbial imbalance with harmful bacteria species outcompeting benign bacteria, can lead to maladies including cancer. The microbial composition varies across body sites, with the gut, urogenital, and skin microbiomes particularly well characterized. However, the microbiome associated with normal breast tissue and breast diseases is poorly understood. Collectively, studies have shown that breast tissue has a distinct microbiome with particular species enriched in the breast tissue itself, as well as the nipple aspirate and gut bacteria of women with breast cancer. More importantly, the breast and associated microbiomes may modulate therapeutic response and serve as potential biomarkers for diagnosing and staging breast cancer.}, }
@article {pmid31455640, year = {2019}, author = {Creekmore, BC and Gray, JH and Walton, WG and Biernat, KA and Little, MS and Xu, Y and Liu, J and Gharaibeh, RZ and Redinbo, MR}, title = {Mouse Gut Microbiome-Encoded β-Glucuronidases Identified Using Metagenome Analysis Guided by Protein Structure.}, journal = {mSystems}, volume = {4}, number = {4}, pages = {}, pmid = {31455640}, issn = {2379-5077}, support = {R01 CA098468/CA/NCI NIH HHS/United States ; R01 CA207416/CA/NCI NIH HHS/United States ; }, abstract = {Gut microbial β-glucuronidase (GUS) enzymes play important roles in drug efficacy and toxicity, intestinal carcinogenesis, and mammalian-microbial symbiosis. Recently, the first catalog of human gut GUS proteins was provided for the Human Microbiome Project stool sample database and revealed 279 unique GUS enzymes organized into six categories based on active-site structural features. Because mice represent a model biomedical research organism, here we provide an analogous catalog of mouse intestinal microbial GUS proteins-a mouse gut GUSome. Using metagenome analysis guided by protein structure, we examined 2.5 million unique proteins from a comprehensive mouse gut metagenome created from several mouse strains, providers, housing conditions, and diets. We identified 444 unique GUS proteins and organized them into six categories based on active-site features, similarly to the human GUSome analysis. GUS enzymes were encoded by the major gut microbial phyla, including Firmicutes (60%) and Bacteroidetes (21%), and there were nearly 20% for which taxonomy could not be assigned. No differences in gut microbial gus gene composition were observed for mice based on sex. However, mice exhibited gus differences based on active-site features associated with provider, location, strain, and diet. Furthermore, diet yielded the largest differences in gus composition. Biochemical analysis of two low-fat-associated GUS enzymes revealed that they are variable with respect to their efficacy of processing both sulfated and nonsulfated heparan nonasaccharides containing terminal glucuronides.IMPORTANCE Mice are commonly employed as model organisms of mammalian disease; as such, our understanding of the compositions of their gut microbiomes is critical to appreciating how the mouse and human gastrointestinal tracts mirror one another. GUS enzymes, with importance in normal physiology and disease, are an attractive set of proteins to use for such analyses. Here we show that while the specific GUS enzymes differ at the sequence level, a core GUSome functionality appears conserved between mouse and human gastrointestinal bacteria. Mouse strain, provider, housing location, and diet exhibit distinct GUSomes and gus gene compositions, but sex seems not to affect the GUSome. These data provide a basis for understanding the gut microbial GUS enzymes present in commonly used laboratory mice. Further, they demonstrate the utility of metagenome analysis guided by protein structure to provide specific sets of functionally related proteins from whole-genome metagenome sequencing data.}, }
@article {pmid31455639, year = {2019}, author = {Cao, L and Shcherbin, E and Mohimani, H}, title = {A Metabolome- and Metagenome-Wide Association Network Reveals Microbial Natural Products and Microbial Biotransformation Products from the Human Microbiota.}, journal = {mSystems}, volume = {4}, number = {4}, pages = {}, pmid = {31455639}, issn = {2379-5077}, support = {DP2 GM137413/GM/NIGMS NIH HHS/United States ; }, abstract = {The human microbiome consists of thousands of different microbial species, and tens of thousands of bioactive small molecules are associated with them. These associated molecules include the biosynthetic products of microbiota and the products of microbial transformation of host molecules, dietary components, and pharmaceuticals. The existing methods for characterization of these small molecules are currently time consuming and expensive, and they are limited to the cultivable bacteria. Here, we propose a method for detecting microbiota-associated small molecules based on the patterns of cooccurrence of molecular and microbial features across multiple microbiomes. We further map each molecule to the clade in a phylogenetic tree that is responsible for its production/transformation. We applied our proposed method to the tandem mass spectrometry and metagenomics data sets collected by the American Gut Project and to microbiome isolates from cystic fibrosis patients and discovered the genes in the human microbiome responsible for the production of corynomycolenic acid, which serves as a ligand for human T cells and induces a specific immune response against infection. Moreover, our method correctly associated pseudomonas quinolone signals, tyrvalin, and phevalin with their known biosynthetic gene clusters.IMPORTANCE Experimental advances have enabled the acquisition of tandem mass spectrometry and metagenomics sequencing data from tens of thousands of environmental/host-oriented microbial communities. Each of these communities contains hundreds of microbial features (corresponding to microbial species) and thousands of molecular features (corresponding to microbial natural products). However, with the current technology, it is very difficult to identify the microbial species responsible for the production/biotransformation of each molecular feature. Here, we develop association networks, a new approach for identifying the microbial producer/biotransformer of natural products through cooccurrence analysis of metagenomics and mass spectrometry data collected on multiple microbiomes.}, }
@article {pmid31448542, year = {2020}, author = {Brüssow, H}, title = {Problems with the concept of gut microbiota dysbiosis.}, journal = {Microbial biotechnology}, volume = {13}, number = {2}, pages = {423-434}, pmid = {31448542}, issn = {1751-7915}, mesh = {Dysbiosis ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; *Microbiota ; Symbiosis ; }, abstract = {The human microbiome research is with the notable exception of fecal transplantation still mostly in a descriptive phase. Part of the difficulty for translating research into medical interventions is due to the large compositional complexity of the microbiome resulting in datasets that need sophisticated statistical methods for their analysis and do not lend to industrial applications. Another part of the difficulty might be due to logical flaws in terminology particularly concerning 'dysbiosis' that avoids circular conclusions and is based on sound ecological and evolutionary reasoning. Many case-control studies are underpowered necessitating more meta-analyses that sort out consistent from spurious dysbiosis-disease associations. We also need for the microbiome a transition from statistical associations to causal relationships with diseases that fulfil a set of modified Koch's postulates for commensals. Disturbingly, the most sophisticated statistical analyses explain only a small percentage of the variance in the microbiome. Microbe-microbe interactions irrelevant to the host and stochastic processes might play a greater role than anticipated. To satisfy the concept of Karl Popper about conjectures and refutations in the scientific process, we should also conduct more experiments that try to refute the role of the commensal gut microbiota for human health and disease.}, }
@article {pmid31443276, year = {2019}, author = {Satokari, R}, title = {Modulation of Gut Microbiota for Health by Current and Next-Generation Probiotics.}, journal = {Nutrients}, volume = {11}, number = {8}, pages = {}, pmid = {31443276}, issn = {2072-6643}, support = {304490, 323156//Academy of Finland/International ; Senior Fellow Grant//Sigrid Jus&#xe9;liuksen S&#xe4;&#xe4;ti&#xf6;/International ; }, mesh = {Dysbiosis ; *Gastrointestinal Microbiome ; Humans ; Prebiotics ; *Probiotics ; *Synbiotics ; }, abstract = {The human gut microbiota is a complex ecosystem and has an essential role in maintaining intestinal and systemic health. Microbiota dysbiosis is associated with a number of intestinal and systemic conditions and its modulation for human health is of great interest. Gut microbiota is a source of novel health-promoting bacteria, often termed as next-generation probiotics in order to distinguish them from traditional probiotics. The previous lessons learned with traditional probiotics can help the development of next-generation probiotics that target specific health issues and needs.}, }
@article {pmid31442396, year = {2019}, author = {Mittelman, K and Burstein, D}, title = {Tiny Hidden Genes within Our Microbiome.}, journal = {Cell}, volume = {178}, number = {5}, pages = {1034-1035}, doi = {10.1016/j.cell.2019.07.039}, pmid = {31442396}, issn = {1097-4172}, mesh = {Bacteria ; Humans ; *Microbiota ; }, abstract = {Exploration of tiny protein-coding sequences within the human microbiome reveals thousands of conserved gene families that have been overlooked by traditional analyses. These small proteins may play key roles in the crosstalk among bacteria within the microbiome and in interactions with their human hosts.}, }
@article {pmid31440433, year = {2019}, author = {Mu, X and Zhao, C and Yang, J and Wei, X and Zhang, J and Liang, C and Gai, Z and Zhang, C and Zhu, D and Wang, Y and Zhang, L}, title = {Group B Streptococcus colonization induces Prevotella and Megasphaera abundance-featured vaginal microbiome compositional change in non-pregnant women.}, journal = {PeerJ}, volume = {7}, number = {}, pages = {e7474}, pmid = {31440433}, issn = {2167-8359}, abstract = {BACKGROUND: Previous studies have indicated that variations in the vaginal microbiome result in symptomatic conditions. Group B Streptococcus (GBS) is a significant neonatal pathogen and maternal vaginal colonization has been recognized as an important risk factor for neonatal disease. Therefore, it is important to discover the relationship between the composition of the vaginal microbiome and GBS colonization. This study explores the potential relationship between the composition of the vaginal microbiome and GBS colonization in non-pregnant Chinese women.<br><br>METHODS: A total of 22 GBS-positive, non-pregnant women and 44 matched GBS-negative women were recruited for the current study. The composition of the vaginal microbiome was profiled by sequencing the 16S rRNA genes. The microbiome diversity and variation were then evaluated.<br><br>RESULTS: The vaginal microbiome of the 66 subjects enrolled in the current study were compared and the results showed that GBS-positive women exhibited significant vaginal microbial differences compared with the GBS-negative women based on the analysis of similarities (r&#xa0;=&#xa0;0.306, p < 0.01). The relative abundance of the bacterial genus Lactobacillus (p < 0.01) was significantly lower in the GBS-positive group, while the abundances of the bacterial genera Prevotella (p < 0.01), Megasphaera (p&#xa0;<&#xa0;0.01), and Streptococcus (p&#xa0;<&#xa0;0.01) were significantly higher in the GBS-positive group.<br><br>DISCUSSION: The current study addressed significant variations across the communities of the vaginal microbiome in GBS-positive and GBS-negative women in a Chinese cohort, which paves the way for a larger cohort-based clinical validation study and the development of therapeutic probiotics in the future.}, }
@article {pmid31440325, year = {2019}, author = {Guo, J and Lv, Q and Ariff, A and Zhang, X and Peacock, CS and Song, Y and Wen, X and Saiganesh, A and Melton, PE and Dykes, GA and Moses, EK and LE Souëf, PN and Lu, F and Zhang, G}, title = {Western oropharyngeal and gut microbial profiles are associated with allergic conditions in Chinese immigrant children.}, journal = {The World Allergy Organization journal}, volume = {12}, number = {8}, pages = {100051}, pmid = {31440325}, issn = {1939-4551}, abstract = {BACKGROUND: The allergy epidemic resulting from western environment/lifestyles is potentially due to modifications of the human microbiome. Therefore, it is of interest to study immigrants living in a western environment as well as their counterparts in the country of origin to understand differences in their microbiomes and health status.<br><br>METHODS: We investigated 58 Australian Chinese (AC) children from Perth, Western Australia as well as 63 Chinese-born Chinese (CC) children from a city in China. Oropharyngeal (OP) and fecal samples were collected. To assess the microbiomes, 16s ribosomal RNA (rRNA) sequencing for variable regions V3 and V4 was used. Skin prick tests (SPT) were performed to measure the children's atopic status. Information on food allergy and wheezing were acquired from a questionnaire.<br><br>RESULTS: AC children had more allergic conditions than CC children. The alpha diversity (mean species diversity) of both OP and gut microbiome was lower in AC children compared to CC children for richness estimate (Chao1), while diversity evenness (Shannon index) was higher. The beta diversity (community similarity) displayed a distinct separation of the OP and gut microbiota between AC and CC children. An apparent difference in microbial abundance was observed for many bacteria. In AC children, we sought to establish consistent trends in bacterial relative abundance that are either higher or lower in AC versus CC children and higher or lower in children with allergy versus those without allergy. The majority of OP taxa showed a consistent trend while the majority of fecal taxa showed a contrasting trend.<br><br>CONCLUSION: Distinct differences in microbiome compositions were found in both oropharyngeal and fecal samples of AC and CC children. The association of the OP microbiome with allergic condition is different from that of the gut microbiome in AC children. The microbiome profiles are changed by the western environment/lifestyle and are associated with allergies in Chinese immigrant children in Australia.}, }
@article {pmid31437194, year = {2019}, author = {Pendegraft, AH and Guo, B and Yi, N}, title = {Bayesian hierarchical negative binomial models for multivariable analyses with applications to human microbiome count data.}, journal = {PloS one}, volume = {14}, number = {8}, pages = {e0220961}, pmid = {31437194}, issn = {1932-6203}, mesh = {Bayes Theorem ; DNA, Bacterial/*genetics ; Databases, Factual ; Gastrointestinal Microbiome/*genetics ; High-Throughput Nucleotide Sequencing ; Humans ; Internet ; Microbial Consortia/*genetics ; Microbiota/*genetics ; Multivariate Analysis ; Phylogeny ; RNA, Ribosomal, 16S/*genetics ; Sequence Analysis, DNA ; }, abstract = {The analyses of large volumes of metagenomic data extracted from aggregate populations of microscopic organisms residing on and in the human body are advancing contemporary understandings of the integrated participation of microbes in human health and disease. Next generation sequencing technology facilitates said analyses in terms of diversity, community composition, and differential abundance by filtering and binning microbial 16S rRNA genes extracted from human tissues into operational taxonomic units. However, current statistical tools restrict study designs to investigations of limited numbers of host characteristics mediated by limited numbers of samples potentially yielding a loss of relevant information. This paper presents a Bayesian hierarchical negative binomial model as an efficient technique capable of compensating for multivariable sets including tens or hundreds of host characteristics as covariates further expanding analyses of human microbiome count data. Simulation studies reveal that the Bayesian hierarchical negative binomial model provides a desirable strategy by often outperforming three competing negative binomial model in terms of type I error while simultaneously maintaining consistent power. An application of the Bayesian hierarchical negative binomial model using subsets of the open data published by the American Gut Project demonstrates an ability to identify operational taxonomic units significantly differentiable among persons diagnosed by a medical professional with either inflammatory bowel disease or irritable bowel syndrome that are consistent with contemporary gastrointestinal literature.}, }
@article {pmid31433970, year = {2019}, author = {Spencer, SP and Fragiadakis, GK and Sonnenburg, JL}, title = {Pursuing Human-Relevant Gut Microbiota-Immune Interactions.}, journal = {Immunity}, volume = {51}, number = {2}, pages = {225-239}, pmid = {31433970}, issn = {1097-4180}, support = {DP1 AT009892/AT/NCCIH NIH HHS/United States ; R01 DK085025/DK/NIDDK NIH HHS/United States ; T32 DK007056/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Gastrointestinal Microbiome/*immunology ; Homeostasis ; *Host-Pathogen Interactions ; Humans ; *Immune System ; Immunity ; Patient-Centered Care ; }, abstract = {The gut microbiota is a complex and plastic network of diverse organisms intricately connected with human physiology. Recent advances in profiling approaches of both the microbiota and the immune system now enable a deeper exploration of immunity-microbiota connections. An important next step is to elucidate a human-relevant "map" of microbial-immune wiring while focusing on animal studies to probe a prioritized subset of interactions. Here, we provide an overview of this field's current status and discuss two approaches for establishing priorities for detailed investigation: (1) longitudinal intervention studies in humans probing the dynamics of both the microbiota and the immune system and (2) the study of traditional populations to assess lost features of human microbial identity whose absence may be contributing to the rise of immunological disorders. These human-centered approaches offer a judicious path forward to understand the impact of the microbiota in immune development and function.}, }
@article {pmid31425594, year = {2019}, author = {Mougeot, JC and Stevens, CB and Morton, DS and Brennan, MT and Mougeot, FB}, title = {Oral Microbiome and Cancer Therapy-Induced Oral Mucositis.}, journal = {Journal of the National Cancer Institute. Monographs}, volume = {2019}, number = {53}, pages = {}, doi = {10.1093/jncimonographs/lgz002}, pmid = {31425594}, issn = {1745-6614}, mesh = {Disease Susceptibility ; Humans ; Intestinal Mucosa/metabolism/microbiology/pathology ; Metagenome ; Metagenomics/methods ; *Microbiota ; Mouth Mucosa/microbiology/pathology ; Neoplasms/*complications/therapy ; Stomatitis/diagnosis/drug therapy/*etiology/prevention &amp; control ; Systems Biology/methods ; }, abstract = {Characterization of the role of oral microbiome in cancer therapy-induced oral mucositis (CTOM) is critical in preventing the clinically deleterious effects on patients' health that are associated with CTOM. Funding initiatives related to the National Institutes of Health human microbiome project have resulted in groundbreaking advancements in biology and medicine during the last decade. These advancements have shown that a human being is in fact a superorganism made of human cells and associated symbiotic or commensal microbiota. In this review, we describe the state of science as it relates to fundamental knowledge on oral microbiome and its role in CTOM. We also discuss how state-of-the-art technologies and systems biology tools may be used to help tackle the difficult challenges ahead to develop effective treatments or preventive therapies for oral mucositis. We make a clear distinction between disease processes pertaining to the oral microbiome, which includes opportunistic pathogens that may be defined as pathobionts, and those infectious disease processes initiated by exogenous pathogens. We also explored the extent to which knowledge from the gastrointestinal tract in disease and intestinal mucositis could help us better understand CTOM pathobiology. Finally, we propose a model in which the oral microbiome participates in the current five-step CTOM pathobiology model. With the advent of more sophisticated metagenomics technologies and methods of analysis, much hope lies ahead to implement an effective holistic approach to treat cancer patients affected by CTOM.}, }
@article {pmid31417531, year = {2019}, author = {Conteville, LC and Oliveira-Ferreira, J and Vicente, ACP}, title = {Gut Microbiome Biomarkers and Functional Diversity Within an Amazonian Semi-Nomadic Hunter-Gatherer Group.}, journal = {Frontiers in microbiology}, volume = {10}, number = {}, pages = {1743}, pmid = {31417531}, issn = {1664-302X}, abstract = {Human groups that still maintain traditional modes of subsistence (hunter-gatherers and rural agriculturalists) represent human groups non-impacted by urban-industrialized lifestyles, and therefore their gut microbiome provides the basis for understanding the human microbiome evolution and its association with human health and disease. The Yanomami is the largest semi-nomadic hunter-gatherer group of the Americas, exploring different niches of the Amazon rainforest in Brazil and Venezuela. Here, based on shotgun metagenomic data, we characterized the gut microbiome of the Yanomami from Brazil and compared taxonomically and functionally with the Yanomami from Venezuela, with other traditional groups from the Amazon and an urban-industrialized group. Taxonomic biomarkers were identified to each South American traditional group studied, including each Yanomami group. Broader levels of functional categories poorly discriminated the traditional and urban-industrialized groups, but the stratification of these categories revealed clear segregation of these groups. The Yanomami/Brazil gut microbiome presented unique functional features, such as a higher abundance of gene families involved in regulation/cell signaling, motility/chemotaxis, and virulence, contrasting with the gut microbiomes from the Yanomami/Venezuela and the other groups. Our study revealed biomarkers, and taxonomic and functional features that distinguished the gut microbiome of Yanomami/Brazil and Yanomami/Venezuela individuals, despite their shared lifestyle, culture, and genetic background. These differences may be a reflection of the environmental and seasonal diversity of the niches they explore. Overall, their microbiome profiles are shared with South American and African traditional groups, probably due to their lifestyle. The unique features identified within the Yanomami highlight the bias imposed by underrepresented sampling, and factors such as variations over space and time (seasonality) that impact, mainly, the hunter-gatherers.}, }
@article {pmid31417492, year = {2019}, author = {Sudo, N}, title = {Biogenic Amines: Signals Between Commensal Microbiota and Gut Physiology.}, journal = {Frontiers in endocrinology}, volume = {10}, number = {}, pages = {504}, pmid = {31417492}, issn = {1664-2392}, abstract = {There is increasing interest in the interactions among the gut microbiota, gut, and brain, which is often referred to as the "microbiota-gut-brain" axis. Biogenic amines including dopamine, norepinephrine, serotonin, and histamines are all generated by commensal gut microorganisms and are suggested to play roles as signaling molecules mediating the function of the "microbiota-gut-brain" axis. In addition, such amines generated in the gut have attracted attention in terms of possible clues into the etiologies of depression, anxiety, and even psychosis. This review covers the latest research related to the potential role of microbe-derived amines such as catecholamine, serotonin, histamine, as well as other trace amines, in modulating not only gut physiology but also brain function of the host. Further attention in this field can offer not only insight into expanding the fundamental roles and impacts of the human microbiome, but also further offer new therapeutic strategies for psychological disorders based on regulating the balance of resident bacteria.}, }
@article {pmid31417479, year = {2019}, author = {Lacorte, E and Gervasi, G and Bacigalupo, I and Vanacore, N and Raucci, U and Parisi, P}, title = {A Systematic Review of the Microbiome in Children With Neurodevelopmental Disorders.}, journal = {Frontiers in neurology}, volume = {10}, number = {}, pages = {727}, pmid = {31417479}, issn = {1664-2295}, abstract = {Background and Purpose: A relationship between gut microbiome and central nervous system (CNS), have been suggested. The human microbiome may have an influence on brain's development, thus implying that dysbiosis may contribute in the etiology and progression of some neurological/neuropsychiatric disorders. The objective of this systematic review was to identify evidence on the characterization and potential distinctive traits of the microbiome of children with neurodevelopmental disorders, as compared to healthy children. Methods: The review was performed following the methodology described in the Cochrane handbook for systematic reviews, and was reported based on the PRISMA statement for reporting systematic reviews and meta-analyses. All literature published up to April 2019 was retrieved searching the databases PubMed, ISI Web of Science and the Cochrane Database of Systematic Reviews. Only observational studies, published in English and reporting data on the characterization of the microbiome in humans aged 0-18 years with a neurodevelopmental disorder were included. Neurodevelopmental disorders were categorized according to the definition included in the Diagnostic and Statistical Manual of Mental Disorders, version 5 (DSM-5). Results: Bibliographic searches yielded 9,237 records. One study was identified through other data sources. A total of 16 studies were selected based on their relevance and pertinence to the topic of the review, and were then applied the predefined inclusion and exclusion criteria. A total of 10 case-control studies met the inclusion criteria, and were thus included in the qualitative analysis and applied the NOS score. Two studies reported data on the gut microbiome of children with ADHD, while 8 reported data on either the gut (n = 6) or the oral microbiome (n = 2) of children with ASD. Conclusions: All the 10 studies included in this review showed a high heterogeneity in terms of sample size, gender, clinical issues, and type of controls. This high heterogeneity, along with the small sample size of the included studies, strongly limited the external validity of results. The quality assessment performed using the NOS score showed an overall low to moderate methodological quality of the included studies. To better clarify the potential role of microbiome in patients with neurodevelopmental disorders, further high-quality observational (specifically cohort) studies are needed.}, }
@article {pmid31415755, year = {2019}, author = {Tierney, BT and Yang, Z and Luber, JM and Beaudin, M and Wibowo, MC and Baek, C and Mehlenbacher, E and Patel, CJ and Kostic, AD}, title = {The Landscape of Genetic Content in the Gut and Oral Human Microbiome.}, journal = {Cell host &amp; microbe}, volume = {26}, number = {2}, pages = {283-295.e8}, pmid = {31415755}, issn = {1934-6069}, support = {R00 ES023504/ES/NIEHS NIH HHS/United States ; R01 AI127250/AI/NIAID NIH HHS/United States ; T32 HG002295/HG/NHGRI NIH HHS/United States ; T32 DK110919/DK/NIDDK NIH HHS/United States ; K99 ES023504/ES/NIEHS NIH HHS/United States ; R21 ES025052/ES/NIEHS NIH HHS/United States ; P30 DK036836/DK/NIDDK NIH HHS/United States ; }, mesh = {Bacteria/classification/genetics ; Biodiversity ; Cluster Analysis ; DNA Fingerprinting ; Databases, Factual ; Gastrointestinal Tract/microbiology ; Genetic Heterogeneity ; Host Microbial Interactions ; Humans ; Metagenome/*genetics ; Metagenomics ; Microbiota/*genetics/*physiology ; Mouth/microbiology ; Multigene Family ; Phenotype ; }, abstract = {Despite substantial interest in the species diversity of the human microbiome and its role in disease, the scale of its genetic diversity, which is fundamental to deciphering human-microbe interactions, has not been quantified. Here, we conducted a cross-study meta-analysis of metagenomes from two human body niches, the mouth and gut, covering 3,655 samples from 13 studies. We found staggering genetic heterogeneity in the dataset, identifying a total of 45,666,334 non-redundant genes (23,961,508 oral and 22,254,436 gut) at the 95% identity level. Fifty percent of all genes were "singletons," or unique to a single metagenomic sample. Singletons were enriched for different functions (compared with non-singletons) and arose from sub-population-specific microbial strains. Overall, these results provide potential bases for the unexplained heterogeneity observed in microbiome-derived human phenotypes. One the basis of these data, we built a resource, which can be accessed at https://microbial-genes.bio.}, }
@article {pmid31410749, year = {2019}, author = {Zhang, F and Wang, M and Yang, J and Xu, Q and Liang, C and Chen, B and Zhang, J and Yang, Y and Wang, H and Shang, Y and Wang, Y and Mu, X and Zhu, D and Zhang, C and Yao, M and Zhang, L}, title = {Response of gut microbiota in type 2 diabetes to hypoglycemic agents.}, journal = {Endocrine}, volume = {66}, number = {3}, pages = {485-493}, pmid = {31410749}, issn = {1559-0100}, mesh = {Aged ; Case-Control Studies ; Diabetes Mellitus, Type 2/*drug therapy/microbiology ; Female ; Gastrointestinal Microbiome/*drug effects ; Humans ; Hyperglycemia/microbiology ; Hypoglycemic Agents/*pharmacology/therapeutic use ; Male ; Middle Aged ; }, abstract = {PURPOSE: Accumulated evidence has indicated that the gut microbiome affected the pharmacology of anti-diabetic agents, and their metabolic products induced by the agents transformed the structure of gastrointestinal microbiota in return. However, the studies around heredity, ethnicity, or living condition, referring to human microbiome were mostly represented by an occidental pattern partial and rare studies that focused on the effect of several first-line hypoglycemic agents on the gut flora in a single medical center. Therefore, we aimed to explore the interaction between gut microbiome and type 2 diabetes (T2D) or hypoglycemics in Chinese population.<br><br>METHODS: A total of 130 T2D patients with a specific hypoglycemic treatment and 50 healthy volunteers were enrolled in this study. Gut microbiome compositons were analyzed by 16S ribosomal RNA gene-based sequencing protocol.<br><br>RESULTS: Hypoglycemic agents contributed to the alteration of specific species in gut bacteria rather than its total diversity. Metformin increased the abundance of Spirochaete, Turicibacter, and Fusobacterium. Insulin also increased Fusobacterium, and &#x3b1;-glucosidase inhibitors (&#x3b1;-GIs) contributed to the plentitude of Bifidobacterium and Lactobacillus. Both metformin and insulin improved taurine and hypotaurine metabolism, and &#x3b1;-GI promoted several amino acid pathways. Although the community of gut microbiota with metformin and insulin showed similarity, significant differences were available in each diabetic group with hypoglycemia.<br><br>CONCLUSIONS: Gut microbiota is significantly associated with anti-diabetic agents. The gut microbiome and metabolism have shown respective characteristics in different T2D groups, which were also significantly different from the healthy group. This study provides some new insights for identification and exploration of the pathogenesis of T2D.}, }
@article {pmid31409863, year = {2019}, author = {Pereira, EM and de Mattos, CS and Dos Santos, OC and Ferreira, DC and de Oliveira, TLR and Laport, MS and de Oliveira Ferreira, E and Dos Santos, KRN}, title = {Staphylococcus hominis subspecies can be identified by SDS-PAGE or MALDI-TOF MS profiles.}, journal = {Scientific reports}, volume = {9}, number = {1}, pages = {11736}, pmid = {31409863}, issn = {2045-2322}, mesh = {Bacterial Proteins/*metabolism ; *Electrophoresis, Polyacrylamide Gel ; Humans ; *Proteome ; *Proteomics/methods ; *Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization ; Staphylococcus hominis/*classification/*metabolism ; }, abstract = {Staphylococcus hominis is part of the normal human microbiome. Two subspecies, S. hominis hominis (Shh) and S. hominis novobiosepticus (Shn), have clinical significance. Forty-nine S. hominis isolates were analyzed by the MicroScan automated system, SDS-PAGE and MALDI-TOF methods, followed by partial sequencing of the 16S rDNA gene. The trehalose fermentation test, disk diffusion and broth microdilution tests were used to identify (novobiocin test) and access the susceptibility to oxacillin and vancomycin of isolates. The SCCmec elements and genomic diversity were evaluated by PCR and PFGE methods, respectively. Profiles of 28 (57%; 8 Shh and 20 Shn) isolates corroborated with the results found in all the applied methods of identification. The remaining 21 (43%) isolates were phenotypically identified as Shh by MicroScan; however, they were identified as Shn by SDS-PAGE and mass spectral, and confirmed by 16S rDNA sequencing. Among 41 isolates identified as Shn by the molecular and mass spectrometry methods, 19 (41%) were novobiocin-sensitive, and the trehalose test indicated 11 positive isolates, which are considered atypical phenotypic results for this subspecies. In addition, 92.7% of the isolates identified as Shn by these methods carried mecA gene, while only 12.5% of the Shh isolates were positive. Together, the results highlighted the SDS-PAGE and MALDI-TOF MS methods as promising tools for discriminating S. hominis subspecies.}, }
@article {pmid31402904, year = {2019}, author = {Gargiullo, L and Del Chierico, F and D'Argenio, P and Putignani, L}, title = {Gut Microbiota Modulation for Multidrug-Resistant Organism Decolonization: Present and Future Perspectives.}, journal = {Frontiers in microbiology}, volume = {10}, number = {}, pages = {1704}, pmid = {31402904}, issn = {1664-302X}, abstract = {The emergence of antimicrobial resistance (AMR) is of great concern to global public health. Treatment of multi-drug resistant (MDR) infections is a major clinical challenge: the increase in antibiotic resistance leads to a greater risk of therapeutic failure, relapses, longer hospitalizations, and worse clinical outcomes. Currently, there are no validated treatments for many MDR or pandrug-resistant (PDR) infections, and preventing the spread of these pathogens through hospital infection control procedures and antimicrobial stewardship programs is often the only tool available to healthcare providers. Therefore, new solutions to control the colonization of MDR pathogens are urgently needed. In this narrative review, we discuss current knowledge of microbiota-mediated mechanisms of AMR and strategies for MDR colonization control. We focus particularly on fecal microbiota transplantation for MDR intestinal decolonization and report updated literature on its current clinical use.}, }
@article {pmid31402586, year = {2019}, author = {Mora, D and Filardi, R and Arioli, S and Boeren, S and Aalvink, S and de Vos, WM}, title = {Development of omics-based protocols for the microbiological characterization of multi-strain formulations marketed as probiotics: the case of VSL#3.}, journal = {Microbial biotechnology}, volume = {12}, number = {6}, pages = {1371-1386}, pmid = {31402586}, issn = {1751-7915}, mesh = {Bacterial Proteins/analysis/isolation &amp; purification ; DNA, Bacterial/chemistry/genetics/isolation &amp; purification ; High-Throughput Nucleotide Sequencing ; Metagenomics/*methods ; Microbial Viability ; Microbiological Techniques/*methods ; Probiotics/*analysis ; Proteomics/*methods ; Technology, Pharmaceutical/*methods/standards ; Urease/analysis ; beta-Galactosidase/analysis ; }, abstract = {The growing commercial interest in multi-strain formulations marketed as probiotics has not been accompanied by an equal increase in the evaluation of quality levels of these biotechnological products. The multi-strain product VSL#3 was used as a model to setup a microbiological characterization that could be extended to other formulations with high complexity. Shotgun metagenomics by deep Illumina sequencing was applied to DNA isolated from the commercial VSL#3 product to confirm strains identity safety and composition. Single-cell analysis was used to evaluate the cell viability, and β-galactosidase and urease activity have been used as marker to monitor the reproducibility of the production process. Similarly, these lots were characterized in detail by a metaproteomics approach for which a robust protein extraction protocol was combined with advanced mass spectrometry. The results identified over 1600 protein groups belonging to all strains present in the VSL#3 formulation. Of interest, only 3.2 % proteins showed significant differences mainly related to small variations in strain abundance. The protocols developed in this study addressed several quality criteria that are relevant for marketed multi-strain products and these represent the first efforts to define the quality of complex probiotic formulations such as VSL#3.}, }
@article {pmid31402174, year = {2019}, author = {Sberro, H and Fremin, BJ and Zlitni, S and Edfors, F and Greenfield, N and Snyder, MP and Pavlopoulos, GA and Kyrpides, NC and Bhatt, AS}, title = {Large-Scale Analyses of Human Microbiomes Reveal Thousands of Small, Novel Genes.}, journal = {Cell}, volume = {178}, number = {5}, pages = {1245-1259.e14}, pmid = {31402174}, issn = {1097-4172}, support = {K08 CA184420/CA/NCI NIH HHS/United States ; P30 CA124435/CA/NCI NIH HHS/United States ; S10 OD023452/OD/NIH HHS/United States ; T32 HG000044/HG/NHGRI NIH HHS/United States ; }, mesh = {Amino Acid Sequence ; Cell Communication ; Host-Pathogen Interactions ; Humans ; Metagenome ; *Microbiota ; Open Reading Frames/genetics ; Proteins/chemistry/*metabolism ; Ribosomal Proteins/chemistry/metabolism ; Sequence Alignment ; }, abstract = {Small proteins are traditionally overlooked due to computational and experimental difficulties in detecting them. To systematically identify small proteins, we carried out a comparative genomics study on 1,773 human-associated metagenomes from four different body sites. We describe >4,000 conserved protein families, the majority of which are novel; ∼30% of these protein families are predicted to be secreted or transmembrane. Over 90% of the small protein families have no known domain and almost half are not represented in reference genomes. We identify putative housekeeping, mammalian-specific, defense-related, and protein families that are likely to be horizontally transferred. We provide evidence of transcription and translation for a subset of these families. Our study suggests that small proteins are highly abundant and those of the human microbiome, in particular, may perform diverse functions that have not been previously reported.}, }
@article {pmid31396188, year = {2019}, author = {Hietala, V and Horsma-Heikkinen, J and Carron, A and Skurnik, M and Kiljunen, S}, title = {The Removal of Endo- and Enterotoxins From Bacteriophage Preparations.}, journal = {Frontiers in microbiology}, volume = {10}, number = {}, pages = {1674}, pmid = {31396188}, issn = {1664-302X}, abstract = {The production of phages for therapeutic purposes demands fast, efficient and scalable purification procedures. Phage lysates have a wide range of impurities, of which endotoxins of gram-negative bacteria and protein toxins produced by many pathogenic bacterial species are harmful to humans. The highest allowed endotoxin concentration for parenterally applied medicines is 5 EU/kg/h. The aim of this study was to evaluate the feasibility of different purification methods in endotoxin and protein toxin removal in the production of phage preparations for clinical use. In the purification assays, we utilized three phages: Escherichia phage vB_EcoM_fHoEco02, Acinetobacter phage vB_ApiM_fHyAci03, and Staphylococcus phage vB_SauM_fRuSau02. The purification methods tested in the study were precipitation with polyethylene glycol, ultracentrifugation, ultrafiltration, anion exchange chromatography, octanol extraction, two different endotoxin removal columns, and different combinations thereof. The efficiency of the applied purification protocols was evaluated by measuring phage titer and either endotoxins or staphylococcal enterotoxins A and C (SEA and SEC, respectively) from samples taken from different purification steps. The most efficient procedure in endotoxin removal was the combination of ultrafiltration and EndoTrap HD affinity column, which was able to reduce the endotoxin-to-phage ratio of vB_EcoM_fHoEco02 lysate from 3.5 × 10[4] Endotoxin Units (EU)/10[9] plaque forming units (PFU) to 0.09 EU/10[9] PFU. The combination of ultrafiltration and anion exchange chromatography resulted in ratio 96 EU/10[9] PFU, and the addition of octanol extraction step into this procedure still reduced this ratio threefold. The other methods tested either resulted to less efficient endotoxin removal or required the use of harmful chemicals that should be avoided when producing phage preparations for medical use. Ultrafiltration with 100,000 MWCO efficiently removed enterotoxins from vB_SauM_fRuSau02 lysate (from 1.3 to 0.06 ng SEA/10[9] PFU), and anion exchange chromatography reduced the enterotoxin concentration below 0.25 ng/ml, the detection limit of the assay.}, }
@article {pmid31388693, year = {2020}, author = {Stoyancheva, G}, title = {Study of helveticin gene in Lactobacillus crispatus strains and evaluation of its use as a phylogenetic marker.}, journal = {Archives of microbiology}, volume = {202}, number = {1}, pages = {205-208}, doi = {10.1007/s00203-019-01711-2}, pmid = {31388693}, issn = {1432-072X}, mesh = {*Genetic Markers/genetics ; Humans ; Lactobacillus/*genetics ; Lactobacillus crispatus/*classification/*genetics ; *Microbiota ; *Phylogeny ; Probiotics/classification ; }, abstract = {Lactobacilli are a part of the human microbiome in healthy humans. Studies of their physiological and genetic characteristics are the basis for their use in probiotic preparations. This report is a brief description of the helveticin gene found in two Lactobacillus crispatus strains, which are a part of the human microbiome. Our analysis showed that the two variants of the gene are not solely characteristic of strains isolated from humans. In the phylogenetic analysis, we found that the studied sequence (this gene) showed a significant difference between the species of the genus Lactobacillus and could be used as a phylogenetic marker.}, }
@article {pmid31387651, year = {2019}, author = {Roura, E and Depoortere, I and Navarro, M}, title = {Review: Chemosensing of nutrients and non-nutrients in the human and porcine gastrointestinal tract.}, journal = {Animal : an international journal of animal bioscience}, volume = {13}, number = {11}, pages = {2714-2726}, doi = {10.1017/S1751731119001794}, pmid = {31387651}, issn = {1751-732X}, mesh = {Animals ; Appetite ; Carbohydrate Metabolism ; Cholecystokinin/metabolism ; Enteroendocrine Cells/metabolism ; *Food Preferences ; *Gastrointestinal Microbiome ; Gastrointestinal Tract/microbiology/physiology ; Ghrelin/metabolism ; Glucagon-Like Peptide 1/metabolism ; Humans ; Intestinal Mucosa/metabolism ; Nutrients ; Peptide YY/metabolism ; Swine/microbiology/*physiology ; Taste ; }, abstract = {The gastrointestinal tract (GIT) is an interface between the external and internal milieus that requires continuous monitoring for nutrients or pathogens and toxic chemicals. The study of the physiological/molecular mechanisms, mediating the responses to the monitoring of the GIT contents, has been referred to as chemosensory science. While most of the progress in this area of research has been obtained in laboratory rodents and humans, significant steps forward have also been reported in pigs. The objective of this review was to update the current knowledge on nutrient chemosensing in pigs in light of recent advances in humans and laboratory rodents. A second objective relates to informing the existence of nutrient sensors with their functionality, particularly linked to the gut peptides relevant to the onset/offset of appetite. Several cell types of the intestinal epithelium such as Paneth, goblet, tuft and enteroendocrine cells (EECs) contain subsets of chemosensory receptors also found on the tongue as part of the taste system. In particular, EECs show specific co-expression patterns between nutrient sensors and/or transceptors (transport proteins with sensing functions) and anorexigenic hormones such as cholecystokinin (CCK), peptide tyrosine tyrosine (PYY) or glucagon-like peptide-1 (GLP-1), amongst others. In addition, the administration of bitter compounds has an inhibitory effect on GIT motility and on appetite through GLP-1-, CCK-, ghrelin- and PYY-labelled EECs in the human small intestine and colon. Furthermore, the mammalian chemosensory system is the target of some bacterial metabolites. Recent studies on the human microbiome have discovered that commensal bacteria have developed strategies to stimulate chemosensory receptors and trigger host cellular functions. Finally, the study of gene polymorphisms related to nutrient sensors explains differences in food choices, food intake and appetite between individuals.}, }
@article {pmid31383276, year = {2019}, author = {Chu, DM and Valentine, GC and Seferovic, MD and Aagaard, KM}, title = {The Development of the Human Microbiome: Why Moms Matter.}, journal = {Gastroenterology clinics of North America}, volume = {48}, number = {3}, pages = {357-375}, pmid = {31383276}, issn = {1558-1942}, support = {R01 DK089201/DK/NIDDK NIH HHS/United States ; R01 HD091731/HD/NICHD NIH HHS/United States ; R21 ES029462/ES/NIEHS NIH HHS/United States ; }, mesh = {Female ; Fetus/*microbiology ; Humans ; Infant, Newborn ; Maternal Nutritional Physiological Phenomena ; *Microbiota ; Pregnancy ; Uterus/microbiology ; }, abstract = {The human body is cohabitated with trillions of commensal bacteria that are essential for our health. However, certain bacteria can also cause diseases in the human host. Before the microbiome can be attributed to disease risk and pathogenesis, normal acquisition and development of the microbiome must be understood. Here, we explore the evidence surrounding in utero microbial exposures and the significant of this exposure in the proper development of the fetal and neonatal microbiome. We further explore the development of the fetal and neonatal microbiome and its relationship to preterm birth, feeding practices, and mode of delivery, and maternal diet.}, }
@article {pmid31379797, year = {2019}, author = {Lo Presti, A and Zorzi, F and Del Chierico, F and Altomare, A and Cocca, S and Avola, A and De Biasio, F and Russo, A and Cella, E and Reddel, S and Calabrese, E and Biancone, L and Monteleone, G and Cicala, M and Angeletti, S and Ciccozzi, M and Putignani, L and Guarino, MPL}, title = {Fecal and Mucosal Microbiota Profiling in Irritable Bowel Syndrome and Inflammatory Bowel Disease.}, journal = {Frontiers in microbiology}, volume = {10}, number = {}, pages = {1655}, pmid = {31379797}, issn = {1664-302X}, abstract = {An imbalance in the bacterial species resulting in the loss of intestinal homeostasis has been described in inflammatory bowel diseases (IBD) and irritable bowel syndrome (IBS). In this prospective study, we investigated whether IBD and IBS patients exhibit specific changes in richness and distribution of fecal and mucosal-associated microbiota. Additionally, we assessed potential 16S rRNA gene amplicons biomarkers for IBD, IBS, and controls (CTRLs) by comparison of taxonomic composition. The relative abundance of bacteria, at phylum and genus/species levels, and the bacterial diversity were determined through 16S rRNA sequence-based fecal and mucosal microbiota analysis. Linear discriminant analysis effect size (LEfSe) was used for biomarker discovery associated to IBD and IBS as compared to CTRLs. In fecal and mucosal samples, the microbiota richness was characterized by a microbial diversity reduction, going from CTRLs to IBS to IBD. β-diversity analysis showed a clear separation between IBD and CTRLs and between IBD and IBS with no significant separation between IBS and CTRLs. β-diversity showed a clear separation between mucosa and stool samples in all the groups. In IBD, there was no difference between inflamed and not inflamed mucosa. Based upon the LEfSe data, the Anaerostipes and Ruminococcaceae were identified as the most differentially abundant bacterial taxa in CTRLs. Erysipelotrichi was identified as potential biomarker for IBS, while Gammaproteobacteria, Enterococcus, and Enterococcaceae for IBD. This study provides an overview of the alterations of microbiota and may aid in identifying potential 16S rRNA gene amplicons mucosal biomarkers for IBD and IBS.}, }
@article {pmid31378678, year = {2019}, author = {Colosimo, DA and Kohn, JA and Luo, PM and Piscotta, FJ and Han, SM and Pickard, AJ and Rao, A and Cross, JR and Cohen, LJ and Brady, SF}, title = {Mapping Interactions of Microbial Metabolites with Human G-Protein-Coupled Receptors.}, journal = {Cell host &amp; microbe}, volume = {26}, number = {2}, pages = {273-282.e7}, pmid = {31378678}, issn = {1934-6069}, support = {P30 CA008748/CA/NCI NIH HHS/United States ; P30 DK020541/DK/NIDDK NIH HHS/United States ; R01 AT009562/AT/NCCIH NIH HHS/United States ; }, mesh = {Angiogenic Proteins/agonists ; Animals ; Bacteria/*metabolism ; Cadaverine/metabolism/pharmacology ; Fatty Acids/metabolism/pharmacology ; Fermentation ; Germ-Free Life ; Histamine Agonists ; Host Microbial Interactions/*immunology/*physiology ; Humans ; Immune System ; Ligands ; Mice ; Mice, Inbred C57BL ; Microbiota/*immunology/*physiology ; Models, Animal ; Propionates/metabolism/pharmacology ; Receptors, G-Protein-Coupled/*agonists/metabolism ; Receptors, Histamine/drug effects ; Receptors, Neurotransmitter/agonists ; }, abstract = {Despite evidence linking the human microbiome to health and disease, how the microbiota affects human physiology remains largely unknown. Microbiota-encoded metabolites are expected to play an integral role in human health. Therefore, assigning function to these metabolites is critical to understanding these complex interactions and developing microbiota-inspired therapies. Here, we use large-scale functional screening of molecules produced by individual members of a simplified human microbiota to identify bacterial metabolites that agonize G-protein-coupled receptors (GPCRs). Multiple metabolites, including phenylpropanoic acid, cadaverine, 9-10-methylenehexadecanoic acid, and 12-methyltetradecanoic acid, were found to interact with GPCRs associated with diverse functions within the nervous and immune systems, among others. Collectively, these metabolite-receptor pairs indicate that diverse aspects of human health are potentially modulated by structurally simple metabolites arising from primary bacterial metabolism.}, }
@article {pmid31370220, year = {2019}, author = {Vitetta, L and Llewellyn, H and Oldfield, D}, title = {Gut Dysbiosis and the Intestinal Microbiome: Streptococcus thermophilus a Key Probiotic for Reducing Uremia.}, journal = {Microorganisms}, volume = {7}, number = {8}, pages = {}, pmid = {31370220}, issn = {2076-2607}, abstract = {In the intestines, probiotics can produce antagonistic effects such as antibiotic-like compounds, bactericidal proteins such as bacteriocins, and encourage the production of metabolic end products that may assist in preventing infections from various pathobionts (capable of pathogenic activity) microbes. Metabolites produced by intestinal bacteria and the adoptions of molecular methods to cross-examine and describe the human microbiome have refreshed interest in the discipline of nephology. As such, the adjunctive administration of probiotics for the treatment of chronic kidney disease (CKD) posits that certain probiotic bacteria can reduce the intestinal burden of uremic toxins. Uremic toxins eventuate from the over manifestation of glucotoxicity and lipotoxicity, increased activity of the hexosamine and polyol biochemical and synthetic pathways. The accumulation of advanced glycation end products that have been regularly associated with a dysbiotic colonic microbiome drives the overproduction of uremic toxins in the colon and the consequent local pro-inflammatory processes. Intestinal dysbiosis associated with significant shifts in abundance and diversity of intestinal bacteria with a resultant and maintained uremia promoting an uncontrolled mucosal pro-inflammatory state. In this narrative review we further address the efficacy of probiotics and highlighted in part the probiotic bacterium Streptococcus thermophilus as an important modulator of uremic toxins in the gut of patients diagnosed with chronic kidney disease. In conjunction with prudent nutritional practices it may be possible to prevent the progression of CKD and significantly downregulate mucosal pro-inflammatory activity with the administration of probiotics that contain S. thermophilus.}, }
@article {pmid31367386, year = {2019}, author = {Fall, NS and Lo, CI and Fournier, PE and Sokhna, C and Raoult, D and Fenollar, F and Lagier, JC}, title = {Arcanobacterium ihumii sp. nov., Varibaculum vaginae sp. nov. and Tessaracoccus timonensis sp. nov., isolated from vaginal swabs from healthy Senegalese women.}, journal = {New microbes and new infections}, volume = {31}, number = {}, pages = {100585}, pmid = {31367386}, issn = {2052-2975}, abstract = {Culturomics studies the microbial variety of the human microbiome by combining diversified culture conditions, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and 16S rRNA gene identification. This study identifies three putative new bacterial species: Arcanobacterium ihumii sp. nov. strain Marseille-P5647[T], Varibaculum vaginae sp. nov. strain Marseille-P5644[T] and Tessaracoccus timonensis sp. nov. strain Marseille-P5995[T], which we describe according to the concept of taxonogenomics.}, }
@article {pmid31354638, year = {2019}, author = {Yin, G and Xia, Y}, title = {Assessing the Hybrid Effects of Neutral and Niche Processes on Gut Microbiome Influenced by HIV Infection.}, journal = {Frontiers in microbiology}, volume = {10}, number = {}, pages = {1467}, pmid = {31354638}, issn = {1664-302X}, abstract = {That both stochastic neutral and deterministic niche forces are in effect in shaping the community assembly and diversity maintenance is becoming an increasingly important consensus. However, assessing the effects of disease on the balance between the two forces in the human microbiome has not been explored to the best of our knowledge. In this article, we applied a hybrid model to address this issue by analyzing the potential effect of HIV infection on the human gut microbiome and adopted a further step of multimodality testing to improve the interpretation of their model. Our study revealed that although niche process is the dominant force in shaping human gut microbial communities, niche process- and neutral process-driven taxa could coexist in the same microbiome, confirming the notion of their joint responsibility. However, we failed to detect the effect of HIV infection in changing the balance. This suggests that the rule governing community assembly and diversity maintenance may be changed by the disturbance from HIV infection-caused dysbiosis. Although we admit that the general question of disease effect on community assembly and diversity maintenance may still be an open question, our study presents the first piece of evidence to reject the significant influence of diseases.}, }
@article {pmid31339096, year = {2019}, author = {Pietilä, JP and Meri, T and Siikamäki, H and Tyyni, E and Kerttula, AM and Pakarinen, L and Jokiranta, TS and Kantele, A}, title = {Dientamoeba fragilis - the most common intestinal protozoan in the Helsinki Metropolitan Area, Finland, 2007 to 2017.}, journal = {Euro surveillance : bulletin Europeen sur les maladies transmissibles = European communicable disease bulletin}, volume = {24}, number = {29}, pages = {}, pmid = {31339096}, issn = {1560-7917}, mesh = {Abdominal Pain ; Adult ; Animals ; Diarrhea/*parasitology ; Dientamoeba/genetics/*isolation &amp; purification ; Dientamoebiasis/*epidemiology/parasitology/transmission ; Feces/*parasitology ; Female ; Finland/epidemiology ; Giardiasis/*epidemiology ; Humans ; Male ; Middle Aged ; Polymerase Chain Reaction ; Retrospective Studies ; Sex Distribution ; }, abstract = {BackgroundDespite the global distribution of the intestinal protozoan Dientamoeba fragilis, its clinical picture remains unclear. This results from underdiagnosis: microscopic screening methods either lack sensitivity (wet preparation) or fail to reveal Dientamoeba (formalin-fixed sample).AimIn a retrospective study setting, we characterised the clinical picture of dientamoebiasis and compared it with giardiasis. In addition, we evaluated an improved approach to formalin-fixed samples for suitability in Dientamoeba diagnostics.MethodsThis study comprised four parts: (i) a descriptive part scrutinising rates of Dientamoeba findings; (ii) a methodological part analysing an approach to detect Dientamoeba-like structures in formalin samples; (iii) a clinical part comparing demographics and symptoms between patients with dientamoebiasis (n = 352) and giardiasis (n = 272), and (iv) a therapeutic part (n = 89 patients) investigating correlation between faecal eradication and clinical improvement.ResultsThe rate of Dientamoeba findings increased 20-fold after introducing criteria for Dientamoeba-like structures in formalin-fixed samples (88.9% sensitivity and 83.3% specificity). A further increase was seen after implementing faecal PCR. Compared with patients with giardiasis, the symptoms in the Dientamoeba group lasted longer and more often included abdominal pain, cramping, faecal urgency and loose rather than watery stools. Resolved symptoms correlated with successful faecal eradication (p < 0.001).ConclusionsPreviously underdiagnosed, Dientamoeba has become the most frequently recorded pathogenic enteroparasite in Finland. This presumably results from improved diagnostics with either PCR or detection of Dientamoeba-like structures in formalin-fixed samples, an approach applicable also in resource-poor settings. Symptoms of dientamoebiasis differ slightly from those of giardiasis; patients with distressing symptoms require treatment.}, }
@article {pmid31338330, year = {2019}, author = {Dong, Z and Chen, B and Pan, H and Wang, D and Liu, M and Yang, Y and Zou, M and Yang, J and Xiao, K and Zhao, R and Zheng, X and Zhang, L and Zhang, Y}, title = {Detection of Microbial 16S rRNA Gene in the Serum of Patients With Gastric Cancer.}, journal = {Frontiers in oncology}, volume = {9}, number = {}, pages = {608}, pmid = {31338330}, issn = {2234-943X}, abstract = {Aberrance in the blood bacterial microbiome has been identified and validated in several non-infectious diseases, including cancer. The occurrence and progression of gastric cancer has been found to be associated with alterations in the microbiome composition. However, the composition of the blood microbiome in patients with gastric cancer is not well-characterized. To test this hypothesis, we conducted a case-control study to investigate the microbiota compositions in the serum of patients with gastric cancer. The serum microbiome was investigated in patients with gastric cancer, atypical hyperplasia, chronic gastritis, and in healthy controls using 16S rRNA gene sequencing targeting the V1-V2 region. Our results revealed that the structure of the serum microbiome in gastric cancer was significantly different from all other groups, and alpha diversity decreased from the healthy control to patients with gastric cancer. The serum microbiome correlated significantly with tumor-node-metastasis (TNM) stage, lymphatic metastasis, tumor diameter, and invasion depth in gastric cancer. Three genera or species, namely, Acinetobacter, Bacteroides, Haemophilus parainfluenzae, were enriched in patients with gastric cancer, whereas Sphingomonas, Comamonas, and Pseudomonas stutzeri were enriched in the healthy control. Furthermore, the structure of serum microbiota differed between gastric cancer lymphatic metastasis and non-lymphatic metastasis. As a pilot investigation to characterizing the serum microbiome in gastric cancer, our study provided a foundation for improving our understanding of the role of microbiota in the pathogenesis of gastric cancer.}, }
@article {pmid31337891, year = {2019}, author = {Kumar, M and Ji, B and Zengler, K and Nielsen, J}, title = {Modelling approaches for studying the microbiome.}, journal = {Nature microbiology}, volume = {4}, number = {8}, pages = {1253-1267}, doi = {10.1038/s41564-019-0491-9}, pmid = {31337891}, issn = {2058-5276}, mesh = {Bacteria/metabolism ; Disease ; Health ; Humans ; Metabolomics ; Metagenome ; Microbial Interactions ; *Microbiota/genetics/physiology ; *Models, Theoretical ; RNA, Ribosomal, 16S/genetics ; }, abstract = {Advances in metagenome sequencing of the human microbiome have provided a plethora of new insights and revealed a close association of this complex ecosystem with a range of human diseases. However, there is little knowledge about how the different members of the microbial community interact with each other and with the host, and we lack basic mechanistic understanding of these interactions related to health and disease. Mathematical modelling has been demonstrated to be highly advantageous for gaining insights into the dynamics and interactions of complex systems and in recent years, several modelling approaches have been proposed to enhance our understanding of the microbiome. Here, we review the latest developments and current approaches, and highlight how different modelling strategies have been applied to unravel the highly dynamic nature of the human microbiome. Furthermore, we discuss present limitations of different modelling strategies and provide a perspective of how modelling can advance understanding and offer new treatment routes to impact human health.}, }
@article {pmid31337077, year = {2019}, author = {Scribano, D and Marzano, V and Levi Mortera, S and Sarshar, M and Vernocchi, P and Zagaglia, C and Putignani, L and Palamara, AT and Ambrosi, C}, title = {Insights into the Periplasmic Proteins of Acinetobacter baumannii AB5075 and the Impact of Imipenem Exposure: A Proteomic Approach.}, journal = {International journal of molecular sciences}, volume = {20}, number = {14}, pages = {}, pmid = {31337077}, issn = {1422-0067}, mesh = {Acinetobacter Infections/microbiology ; Acinetobacter baumannii/*drug effects/*metabolism ; Amino Acids/metabolism ; Anti-Bacterial Agents/*pharmacology ; Bacterial Proteins/genetics/metabolism ; Dose-Response Relationship, Drug ; Drug Resistance, Bacterial ; Gene Expression Regulation, Bacterial/drug effects ; Imipenem/*pharmacology ; Lipid Metabolism/drug effects ; Microbial Sensitivity Tests ; Oxidative Stress ; Periplasmic Proteins/genetics/*metabolism ; Phenotype ; Proteome ; Proteomics/methods ; }, abstract = {Carbapenem-resistant Acinetobacter baumannii strains cause life-threatening infections due to the lack of therapeutic options. Although the main mechanisms underlying antibiotic-resistance have been extensively studied, the general response to maintain bacterial viability under antibiotic exposure deserves to be fully investigated. Since the periplasmic space contains several proteins with crucial cellular functions, besides carbapenemases, we decided to study the periplasmic proteome of the multidrug-resistant (MDR) A. baumannii AB5075 strain, grown in the absence and presence of imipenem (IMP). Through the proteomic approach, 65 unique periplasmic proteins common in both growth conditions were identified: eight proteins involved in protein fate, response to oxidative stress, energy metabolism, antibiotic-resistance, were differentially expressed. Among them, ABUW_1746 and ABUW_2363 gene products presented the tetratricopeptide repeat motif, mediating protein-protein interactions. The expression switch of these proteins might determine specific protein interactions to better adapt to changing environmental conditions. ABUW_2868, encoding a heat shock protein likely involved in protection against oxidative stress, was upregulated in IMP-exposed bacteria. Accordingly, the addition of periplasmic proteins from A. baumannii cultured with IMP increased bacterial viability in an antioxidant activity assay. Overall, this study provides the first insights about the composition of the periplasmic proteins of a MDR A. baumannii strain, its biological response to IMP and suggests possible new targets to develop alternative antibiotic drugs.}, }
@article {pmid31337018, year = {2019}, author = {Wakabayashi, R and Nakahama, Y and Nguyen, V and Espinoza, JL}, title = {The Host-Microbe Interplay in Human Papillomavirus-Induced Carcinogenesis.}, journal = {Microorganisms}, volume = {7}, number = {7}, pages = {}, pmid = {31337018}, issn = {2076-2607}, abstract = {Every year nearly half a million new cases of cervix cancer are diagnosed worldwide, making this malignancy the fourth commonest cancer in women. In 2018, more than 270,000 women died of cervix cancer globally with 85% of them being from developing countries. The majority of these cancers are caused by the infection with carcinogenic strains of human papillomavirus (HPV), which is also causally implicated in the development of other malignancies, including cancer of the anus, penis cancer and head and neck cancer. HPV is by far the most common sexually transmitted infection worldwide, however, most infected people do not develop cancer and do not even have a persistent infection. The development of highly effective HPV vaccines against most common high-risk HPV strains is a great medical achievement of the 21st century that could prevent up to 90% of cervix cancers. In this article, we review the current understanding of the balanced virus-host interaction that can lead to either virus elimination or the establishment of persistent infection and ultimately malignant transformation. We also highlight the influence of certain factors inherent to the host, including the immune status, genetic variants and the coexistence of other microbe infections and microbiome composition in the dynamic of HPV infection induced carcinogenesis.}, }
@article {pmid31336807, year = {2019}, author = {Hamidi, B and Wallace, K and Alekseyenko, AV}, title = {MODIMA, a Method for Multivariate Omnibus Distance Mediation Analysis, Allows for Integration of Multivariate Exposure-Mediator-Response Relationships.}, journal = {Genes}, volume = {10}, number = {7}, pages = {}, pmid = {31336807}, issn = {2073-4425}, support = {U54 CA210963/CA/NCI NIH HHS/United States ; R01 LM012517/LM/NLM NIH HHS/United States ; U54 CA210962/CA/NCI NIH HHS/United States ; R21 TR002513/TR/NCATS NIH HHS/United States ; UL1 TR001450/TR/NCATS NIH HHS/United States ; }, mesh = {Animals ; Computational Biology/*methods ; Computer Simulation ; Datasets as Topic ; *Gastrointestinal Microbiome ; Humans ; Mice ; *Models, Statistical ; Multivariate Analysis ; }, abstract = {Many important exposure-response relationships, such as diet and weight, can be influenced by intermediates, such as the gut microbiome. Understanding the role of these intermediates, the mediators, is important in refining cause-effect theories and discovering additional medical interventions (e.g., probiotics, prebiotics). Mediation analysis has been at the heart of behavioral health research, rapidly gaining popularity with the biomedical sciences in the last decade. A specific analytic challenge is being able to incorporate an entire 'omics assay as a mediator. To address this challenge, we propose a hypothesis testing framework for multivariate omnibus distance mediation analysis (MODIMA). We use the power of energy statistics, such as partial distance correlation, to allow for analysis of multivariate exposure-mediator-response triples. Our simulation results demonstrate the favorable statistical properties of our approach relative to the available alternatives. Finally, we demonstrate the application of the proposed methods in two previously published microbiome datasets. Our framework adds a new tool to the toolbox of approaches to the integration of 'omics big data.}, }
@article {pmid31328778, year = {2019}, author = {Pebenito, AM and Liu, M and Nazzal, L and Blaser, MJ}, title = {Development of a Humanized Murine Model for the Study of Oxalobacter formigenes Intestinal Colonization.}, journal = {The Journal of infectious diseases}, volume = {220}, number = {11}, pages = {1848-1858}, pmid = {31328778}, issn = {1537-6613}, support = {U54 DK083908/DK/NIDDK NIH HHS/United States ; P30 CA016087/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Carrier State/*microbiology ; Fecal Microbiota Transplantation/methods ; Feces/microbiology ; Gastrointestinal Microbiome ; Gram-Negative Bacterial Infections/*microbiology ; Intestines/*microbiology ; Mice, Inbred C57BL ; *Models, Animal ; Oxalobacter formigenes/*growth &amp; development ; }, abstract = {BACKGROUND: Oxalobacter formigenes are bacteria that colonize the human gut and degrade oxalate, a component of most kidney stones. Findings of clinical and epidemiological studies suggest that O. formigenes colonization reduces the risk for kidney stones. We sought to develop murine models to allow investigating O. formigenes in the context of its native human microbiome.<br><br>METHODS: For humanization, we transplanted pooled feces from healthy, noncolonized human donors supplemented with a human O. formigenes strain into recipient mice. We transplanted microbiota into mice that were treated with broad-spectrum antibiotics to suppress their native microbiome, were germ free, or received humanization without pretreatment or received sham gavage (controls).<br><br>RESULTS: All humanized mice were stably colonized with O. formigenes through 8 weeks after gavage, whereas mice receiving sham gavage remained uncolonized (P < .001). Humanization significantly changed the murine intestinal microbial community structure (P < .001), with humanized germ-free and antibiotic-treated groups overlapping in &#x3b2;-diversity. Both germ-free and antibiotic-treated mice had significantly increased numbers of human species compared with sham-gavaged mice (P < .001).<br><br>CONCLUSIONS: Transplanting mice with human feces and O. formigenes introduced new microbial populations resembling the human microbiome, with stable O. formigenes colonization; such models can define optimal O. formigenes strains to facilitate clinical trials.}, }
@article {pmid31327398, year = {2019}, author = {O'Gorman, DB and Pena-Diaz, AM and Drosdowech, D and Faber, KJ and Athwal, GS and Burton, JP and Al, K and Huang, T and Qiu, B}, title = {Response to Long et al regarding: "Cutibacterium acnes and the shoulder microbiome".}, journal = {Journal of shoulder and elbow surgery}, volume = {28}, number = {8}, pages = {e277-e278}, doi = {10.1016/j.jse.2019.04.047}, pmid = {31327398}, issn = {1532-6500}, mesh = {*Microbiota ; Propionibacterium acnes ; *Shoulder ; }, }
@article {pmid31323792, year = {2019}, author = {Santiago-Rodriguez, TM and Hollister, EB}, title = {Human Virome and Disease: High-Throughput Sequencing for Virus Discovery, Identification of Phage-Bacteria Dysbiosis and Development of Therapeutic Approaches with Emphasis on the Human Gut.}, journal = {Viruses}, volume = {11}, number = {7}, pages = {}, pmid = {31323792}, issn = {1999-4915}, mesh = {Adaptation, Biological ; Animals ; Bacteria/genetics/virology ; Bacteriolysis ; Bacteriophages/physiology ; *Disease Susceptibility ; Dysbiosis ; Gastrointestinal Microbiome ; High-Throughput Nucleotide Sequencing ; *Host-Pathogen Interactions ; Humans ; Metagenomics/methods ; Microbial Interactions ; *Microbiota ; *Viruses/classification/genetics ; }, abstract = {The virome is comprised of endogenous retroviruses, eukaryotic viruses, and bacteriophages and is increasingly being recognized as an essential part of the human microbiome. The human virome is associated with Type-1 diabetes (T1D), Type-2 diabetes (T2D), Inflammatory Bowel Disease (IBD), Human Immunodeficiency Virus (HIV) infection, and cancer. Increasing evidence also supports trans-kingdom interactions of viruses with bacteria, small eukaryotes and host in disease progression. The present review focuses on virus ecology and biology and how this translates mostly to human gut virome research. Current challenges in the field and how the development of bioinformatic tools and controls are aiding to overcome some of these challenges are also discussed. Finally, the present review also focuses on how human gut virome research could result in translational and clinical studies that may facilitate the development of therapeutic approaches.}, }
@article {pmid31322866, year = {2019}, author = {Huddleston, JP and Thoden, JB and Dopkins, BJ and Narindoshvili, T and Fose, BJ and Holden, HM and Raushel, FM}, title = {Structural and Functional Characterization of YdjI, an Aldolase of Unknown Specificity in Escherichia coli K12.}, journal = {Biochemistry}, volume = {58}, number = {31}, pages = {3340-3353}, pmid = {31322866}, issn = {1520-4995}, support = {R01 GM115921/GM/NIGMS NIH HHS/United States ; R01 GM122825/GM/NIGMS NIH HHS/United States ; }, mesh = {Aldehyde-Lyases/*chemistry/*metabolism ; Biocatalysis ; Escherichia coli K12/*enzymology ; Escherichia coli Proteins/*chemistry/*metabolism ; Models, Molecular ; Protein Conformation ; Substrate Specificity ; }, abstract = {The ydj gene cluster is found in 80% of sequenced Escherichia coli genomes and other closely related species in the human microbiome. On the basis of the annotations of the enzymes located in this cluster, it is expected that together they catalyze the catabolism of an unknown carbohydrate. The focus of this investigation is on YdjI, which is in the ydj gene cluster of E. coli K-12. It is predicted to be a class II aldolase of unknown function. Here we describe a structural and functional characterization of this enzyme. YdjI catalyzes the hydrogen/deuterium exchange of the pro-S hydrogen at C3 of dihydroxyacetone phosphate (DHAP). In the presence of DHAP, YdjI catalyzes an aldol condensation with a variety of aldo sugars. YdjI shows a strong preference for higher-order (seven-, eight-, and nine-carbon) monosaccharides with specific hydroxyl stereochemistries and a negatively charged terminus (carboxylate or phosphate). The best substrate is l-arabinuronic acid with an apparent kcat of 3.0 s[-1]. The product, l-glycero-l-galacto-octuluronate-1-phosphate, has a kcat/Km value of 2.1 × 10[3] M[-1] s[-1] in the retro-aldol reaction with YdjI. This is the first recorded synthesis of l-glycero-l-galacto-octuluronate-1-phosphate and six similar carbohydrates. The crystal structure of YdjI, determined to a nominal resolution of 1.75 Å (Protein Data Bank entry 6OFU), reveals unusual positions for two arginine residues located near the active site. Computational docking was utilized to distinguish preferable binding orientations for l-glycero-l-galacto-octuluronate-1-phosphate. These results indicate a possible alternative binding orientation for l-glycero-l-galacto-octuluronate-1-phosphate compared to that observed in other class II aldolases, which utilize shorter carbohydrate molecules.}, }
@article {pmid31321880, year = {2019}, author = {Peters, DL and Wang, W and Zhang, X and Ning, Z and Mayne, J and Figeys, D}, title = {Metaproteomic and Metabolomic Approaches for Characterizing the Gut Microbiome.}, journal = {Proteomics}, volume = {19}, number = {16}, pages = {e1800363}, doi = {10.1002/pmic.201800363}, pmid = {31321880}, issn = {1615-9861}, support = {GPH-129340//CIHR/Canada ; MOP-114872//CIHR/Canada ; }, mesh = {Bacteria/classification/genetics/*metabolism ; Bacterial Proteins/genetics/metabolism ; *Gastrointestinal Microbiome ; Gene Expression Profiling/*methods ; Humans ; Metabolomics/*methods ; *Microbiota ; Neoplasms/genetics/metabolism/microbiology ; Obesity/genetics/metabolism/microbiology ; Proteomics/*methods ; }, abstract = {The gut microbiome has been shown to play a significant role in human healthy and diseased states. The dynamic signaling that occurs between the host and microbiome is critical for the maintenance of host homeostasis. Analyzing the human microbiome with metaproteomics, metabolomics, and integrative multi-omics analyses can provide significant information on markers for healthy and diseased states, allowing for the eventual creation of microbiome-targeted treatments for diseases associated with dysbiosis. Metaproteomics enables functional activity information to be gained from the microbiome samples, while metabolomics provides insight into the overall metabolic states affecting/representing the host-microbiome interactions. Combining these functional -omic platforms together with microbiome composition profiling allows for a holistic overview on the functional and metabolic state of the microbiome and its influence on human health. Here the benefits of metaproteomics, metabolomics, and the integrative multi-omic approaches to investigating the gut microbiome in the context of human health and diseases are reviewed.}, }
@article {pmid31319564, year = {2019}, author = {Ticinesi, A and Nouvenne, A and Cerundolo, N and Catania, P and Prati, B and Tana, C and Meschi, T}, title = {Gut Microbiota, Muscle Mass and Function in Aging: A Focus on Physical Frailty and Sarcopenia.}, journal = {Nutrients}, volume = {11}, number = {7}, pages = {}, pmid = {31319564}, issn = {2072-6643}, mesh = {Aged ; Animals ; *Frailty ; Gastrointestinal Microbiome/*physiology ; Humans ; Muscle, Skeletal/*physiology ; Sarcopenia/*physiopathology ; }, abstract = {Human gut microbiota is able to influence the host physiology by regulating multiple processes, including nutrient absorption, inflammation, oxidative stress, immune function, and anabolic balance. Aging is associated with reduced microbiota biodiversity, increased inter-individual variability, and over-representation of pathobionts, and these phenomena may have great relevance for skeletal muscle mass and function. For this reason, the presence of a gut-muscle axis regulating the onset and progression of age-related physical frailty and sarcopenia has been recently hypothesized. In this narrative review, we summarize the studies supporting a possible association between gut microbiota-related parameters with measures of muscle mass, muscle function, and physical performance in animal models and humans. Reduced muscle mass has been associated with distinct microbiota composition and reduced fermentative capacity in mice, and the administration of probiotics or butyrate to mouse models of muscle wasting has been associated with improved muscle mass. However, no studies have targeted the human microbiome associated with sarcopenia. Limited evidence from human studies shows an association between microbiota composition, involving key taxa such as Faecalibacterium and Bifidobacterium, and grip strength. Similarly, few studies conducted on patients with parkinsonism showed a trend towards a different microbiota composition in those with reduced gait speed. No studies have assessed the association of fecal microbiota with other measures of physical performance. However, several studies, mainly with a cross-sectional design, suggest an association between microbiota composition and frailty, mostly assessed according to the deficit accumulation model. Namely, frailty was associated with reduced microbiota biodiversity, and lower representation of butyrate-producing bacteria. Therefore, we conclude that the causal link between microbiota and physical fitness is still uncertain due to the lack of targeted studies and the influence of a large number of covariates, including diet, exercise, multimorbidity, and polypharmacy, on both microbiota composition and physical function in older age. However, the relationship between gut microbiota and physical function remains a very promising area of research for the future.}, }
@article {pmid31316375, year = {2019}, author = {Novotný, M and Klimova, B and Valis, M}, title = {Microbiome and Cognitive Impairment: Can Any Diets Influence Learning Processes in a Positive Way?.}, journal = {Frontiers in aging neuroscience}, volume = {11}, number = {}, pages = {170}, pmid = {31316375}, issn = {1663-4365}, abstract = {The aim of this review is to summarize the effect of human intestinal microbiome on cognitive impairments and to focus primarily on the impact of diet and eating habits on learning processes. Better understanding of the microbiome could revolutionize the possibilities of therapy for many diseases. The authors performed a literature review of available studies on the research topic describing the influence of human microbiome and diet on cognitive impairment or learning processes found in the world's acknowledged databases Web of Science, PubMed, Springer, and Scopus. The digestive tube is populated by billions of living microorganisms including viruses, bacteria, protozoa, helminths, and microscopic fungi. In adulthood, under physiological conditions, the intestinal microbiome appears to be relatively steady. However, it is not true that it would not be influenced, both in the positive sense of the word and in the negative one. The basic pillars that maintain a steady microbiome are genetics, lifestyle, diet and eating habits, geography, and age. It is reported that the gastrointestinal tract and the brain communicate with each other through several pathways and one can speak about gut-brain axis. New evidence is published every year about the association of intestinal dysbiosis and neurological/psychiatric diseases. On the other hand, specific diets and eating habits can have a positive effect on a balanced microbiota composition and thus contribute to the enhancement of cognitive functions, which are important for any learning process.}, }
@article {pmid31315786, year = {2019}, author = {Zhou, H and Suo, J and Zhu, J}, title = {[Therapeutic Relevance of Human Microbiota and Lung Cancer].}, journal = {Zhongguo fei ai za zhi = Chinese journal of lung cancer}, volume = {22}, number = {7}, pages = {464-469}, pmid = {31315786}, issn = {1999-6187}, mesh = {Carcinogenesis ; Humans ; Lung Neoplasms/*microbiology/pathology/*therapy ; *Microbiota ; }, abstract = {The human microbiome is closely related to human health status. Disruption of the symbiotic balance of the human microbiome is commonly found in systematic diseases such as diabetes, obesity, and chronic gastric diseases. The human microbiome confers benefits or disease susceptibility to the human body through multiple pathways, associated with approximately 20% of malignancies. The incidence and mortality of lung cancer (LC) in men in China are the highest among all malignancies, which is a serious threat to human health. Emerging evidence has suggested that the human microbiota may be closely related to lung cancer at multiple levels, e.g., by affecting metabolic, inflammatory, or immune pathways. At the same time, the human microbiota affects the efficacy of lung cancer on chemoradiotherapy, gene therapy, immunotherapy and other treatments. Immunotherapy is a promising method for the treatment of malignancies such as lung cancer, but the efficacy of immune checkpoint inhibitors in patients is heterogeneous. Preclinical studies based on lung cancer cell lines suggest that the intestinal microbiota can modulate responses to anti--PD-1 therapy through interactions with the host immune system. But for lung cancer patients, whether the intestinal flora can still regulate immunotherapy remains controversial. In this mini-review, we summarize current research findings describing therapeutic relevance of human microbiota and lung cancer. A better knowledge of the interplay between the human microbiome and lung cancer may promote the development of innovative strategies for prevention and personalized treatment in lung cancer.}, }
@article {pmid31312608, year = {2019}, author = {Gallon, P and Parekh, M and Ferrari, S and Fasolo, A and Ponzin, D and Borroni, D}, title = {Metagenomics in ophthalmology: Hypothesis or real prospective?.}, journal = {Biotechnology reports (Amsterdam, Netherlands)}, volume = {23}, number = {}, pages = {e00355}, pmid = {31312608}, issn = {2215-017X}, abstract = {Metagenomic analysis was originally associated with the studies of genetic material from environmental samples. But, with the advent of the Human Microbiome Project, it has now been applied in clinical practices. The ocular surface (OS) is the most exposed part of the eye, colonized by several microbial communities (both, OS and environmental) that contribute to the maintenance of the physiological state. Limited knowledge has been acquired on these microbes due to the limitations of conventional diagnostic methods. Emerging fields of research are focusing on Next Generation Sequencing (NGS) technologies to obtain reliable information on the OS microbiome. Currently only pre-specified pathogens can be detected by conventional culture-based techniques or Polymerase Chain Reaction (PCR), but there are conditions to state whether metagenomics could revolutionize the diagnosis of ocular diseases. The aim of this review is to provide an updated overview of the studies involving NGS technology for OS microbiome.}, }
@article {pmid31307469, year = {2019}, author = {Huang, C and Shi, G}, title = {Smoking and microbiome in oral, airway, gut and some systemic diseases.}, journal = {Journal of translational medicine}, volume = {17}, number = {1}, pages = {225}, pmid = {31307469}, issn = {1479-5876}, mesh = {Disease ; *Gastrointestinal Microbiome ; Humans ; Lung/*microbiology ; *Microbiota ; Mouth/*microbiology ; Smoking/*adverse effects ; }, abstract = {The human microbiome harbors a diverse array of microbes which establishes a mutually beneficial relation with the host in healthy conditions, however, the dynamic homeostasis is influenced by both host and environmental factors. Smoking contributes to modifications of the oral, lung and gut microbiome, leading to various diseases, such as periodontitis, asthma, chronic obstructive pulmonary disease, Crohn's disease, ulcerative colitis and cancers. However, the exact causal relationship between smoking and microbiome alteration remains to be further explored.}, }
@article {pmid31301004, year = {2019}, author = {Li, JKM and Chiu, PKF and Ng, CF}, title = {The impact of microbiome in urological diseases: a systematic review.}, journal = {International urology and nephrology}, volume = {51}, number = {10}, pages = {1677-1697}, pmid = {31301004}, issn = {1573-2584}, mesh = {Humans ; *Microbiota ; Urologic Diseases/*microbiology ; }, abstract = {OBJECTIVE: The term microbiome is used to signify the ecological community of commensal, symbiotic, and pathogenic microorganisms that share our body space, in which there were increasing evidences to suggest that they might have potential roles in various medical conditions. While the study of microbiome in the urinary system is not as robust as the systems included in the Human Microbiome Project, there are still evidences in the literature showing that microbiome may have a role in urological diseases. Therefore, we would like to perform a systematic review on the topic and summarize the available evidence on the impact of microbiome on urological diseases.<br><br>METHODOLOGY: This review was performed according to the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) statement. After screening 589 abstracts and including additional studies (such as references from review papers), 76 studies were included for review and discussion.<br><br>RESULTS: Studies had suggested that there were correlations of microbiome of different body cavities (e.g., fecal, urinary and seminal fluid) with urological diseases. Also, different diseases would have different microbiome profile in different body cavities. Unfortunately, the studies on the association of microbiome and urological diseases were still either weak or inconsistent.<br><br>CONCLUSION: Studies suggested that there might be some relationship between microbiome and various urological diseases. However, further large-scale studies with control of confounding factors should be performed under a standardized methodology in order to have better understanding of the relationship. Also, more standardized reporting protocol for microbiome studies should be considered for better communications in future studies.}, }
@article {pmid31297102, year = {2019}, author = {Zhang, Z and Yang, J and Feng, Q and Chen, B and Li, M and Liang, C and Li, M and Li, Z and Xu, Q and Zhang, L and Chen, W}, title = {Compositional and Functional Analysis of the Microbiome in Tissue and Saliva of Oral Squamous Cell Carcinoma.}, journal = {Frontiers in microbiology}, volume = {10}, number = {}, pages = {1439}, pmid = {31297102}, issn = {1664-302X}, abstract = {Oral squamous cell carcinoma (OSCC) is affected by the interaction between oral pathogen and holobionts, or the combination of the host and its microbial communities. Studies have indicated the structure and feature of the microbiome in OSCC tissue and saliva, the relationships between microbiota and OSCC sites, stages remain unclear. In the present study, OSCC tissue (T), saliva (S) and mouthwash (W) samples were collected from the same subjects and carried out the microbiome study by 16S sequencing. The results showed the T group was significantly different from the S and W groups with the character of lower richness and diversity. Proteobacteria were most enriched in the T group at the phylum level, while Firmicutes were predominant in groups S and W. At the genus level, the predominant taxa of group T were Acinetobacter and Fusobacterium, and for group S and W, the predominant taxa were Streptococcus and Prevotella. The genera related to late stage tumors were Acinetobacter and Fusobacterium, suggesting microbiota may be implicated in OSCC developing. Both compositional and functional analyses indicated that microbes in tumor tissue were potential indicator for the initiation and development of OSCC.}, }
@article {pmid31295421, year = {2019}, author = {Lam, KN and Alexander, M and Turnbaugh, PJ}, title = {Precision Medicine Goes Microscopic: Engineering the Microbiome to Improve Drug Outcomes.}, journal = {Cell host &amp; microbe}, volume = {26}, number = {1}, pages = {22-34}, pmid = {31295421}, issn = {1934-6069}, support = {R01 HL122593/HL/NHLBI NIH HHS/United States ; R21 CA227232/CA/NCI NIH HHS/United States ; T32 AI060537/AI/NIAID NIH HHS/United States ; }, mesh = {Drug Therapy/*methods ; Drug-Related Side Effects and Adverse Reactions ; Humans ; *Microbiota ; Precision Medicine/*methods/trends ; Treatment Outcome ; }, abstract = {Despite the recognition, nearly a century ago, that the human microbiome plays a clinically relevant role in drug disposition, mechanistic insights, and translational applications are still limited. Here, we highlight the recent re-emergence of "pharmacomicrobiomics," which seeks to understand how inter-individual variations in the microbiome shape drug efficacy and side effect profiles. Multiple bacterial species, genes, and enzymes have already been implicated in the direct biotransformation of drugs, both from targeted case studies and from systematic computational and experimental analyses. Indirect mechanisms are also at play; for example, microbial interactions with the host immune system can have broad effects on immunomodulatory drugs. Finally, we discuss multiple emerging strategies for the precise manipulation of complex microbial communities to improve treatment outcomes. In the coming years, we anticipate a shift toward a more comprehensive view of precision medicine that encompasses our human and microbial genomes and their combined metabolic activities.}, }
@article {pmid31292231, year = {2019}, author = {Mike, LA}, title = {mSphere of Influence: Systematically Decoding Microbial Chemical Communication.}, journal = {mSphere}, volume = {4}, number = {4}, pages = {}, pmid = {31292231}, issn = {2379-5042}, mesh = {Bacteria/genetics/*metabolism/pathogenicity ; *Bacterial Physiological Phenomena ; Biosynthetic Pathways/*genetics ; Humans ; *Microbiota ; Multigene Family ; Secondary Metabolism ; }, abstract = {Laura A. Mike works in the field of bacterial pathogenesis. In this mSphere of Influence article, she reflects on how "Insights into Secondary Metabolism from a Global Analysis of Prokaryotic Biosynthetic Gene Clusters" by P. Cimermancic et al. (Cell 158:412-421, 2014, https://doi.org/10.1016/j.cell.2014.06.034) and "A Systematic Analysis of Biosynthetic Gene Clusters in the Human Microbiome Reveals a Common Family of Antibiotics" by M. S. Donia et al. (Cell 158:1402-1414, 2014, https://doi.org/10.1016/j.cell.2014.08.032) made an impact on her by systematically identifying microbiome-associated biosynthetic gene clusters predicted to synthesize secondary metabolites, which may facilitate interspecies interactions.}, }
@article {pmid31288283, year = {2019}, author = {Wree, A and Geisler, LJ and Tacke, F}, title = {[Microbiome &amp; NASH - partners in crime driving progression of fatty liver disease].}, journal = {Zeitschrift fur Gastroenterologie}, volume = {57}, number = {7}, pages = {871-882}, doi = {10.1055/a-0755-2595}, pmid = {31288283}, issn = {1439-7803}, mesh = {Disease Progression ; *Gastrointestinal Microbiome ; Gastrointestinal Tract/*microbiology ; Humans ; Liver Cirrhosis ; *Microbiota ; Non-alcoholic Fatty Liver Disease/*microbiology/pathology ; }, abstract = {Along with the increasing prevalence of obesity, metabolic syndrome and type 2 diabetes, non-alcoholic fatty liver disease (NAFLD) is rapidly increasing and poses a major challenge for gastroenterologists. Many studies have demonstrated that the microbiome is closely associated with the progression of nutrition-related diseases, especially of fatty liver disease. Changes in the quantity and quality of the intestinal flora, commonly referred to as dysbiosis, result in altered food metabolism, increased permeability of the intestinal barrier ("leaky gut") and consecutive inflammatory processes in the liver. This favors both the progression of obesity and metabolic disorders as well as NAFLD towards non-alcoholic steatohepatitis (NASH), hepatic fibrosis, cirrhosis and hepatocellular carcinoma (HCC). Important molecular mechanisms include microbial metabolites, microbial and endogenous signaling substances (so-called PAMPs/DAMPs) as well as bile acids. Essential cellular mechanisms include immune cells in the gut and liver, especially macrophages and Kupffer cells, as well as intestinal epithelial cells and hepatocytes as central regulators of metabolism. In this review article, we briefly summarize the relevant species of the human microbiome, describe the microbial analytics, explain the most important molecular relationships between microbiome and NAFLD/NASH, and finally the opportunities and challenges of microbiome-modulating therapy for the treatment of fatty liver disease.}, }
@article {pmid31284576, year = {2019}, author = {Jackson, BR and Chow, N and Forsberg, K and Litvintseva, AP and Lockhart, SR and Welsh, R and Vallabhaneni, S and Chiller, T}, title = {On the Origins of a Species: What Might Explain the Rise of Candida auris?.}, journal = {Journal of fungi (Basel, Switzerland)}, volume = {5}, number = {3}, pages = {}, pmid = {31284576}, issn = {2309-608X}, abstract = {Candida auris is an emerging multidrug-resistant yeast first described in 2009 that has since caused healthcare-associated outbreaks of severe human infections around the world. In some hospitals, it has become a leading cause of invasive candidiasis. C. auris is markedly different from most other pathogenic Candida species in its genetics, antifungal resistance, and ability to spread between patients. The reasons why this fungus began spreading widely in the last decade remain a mystery. We examine available data on C. auris and related species, including genomic epidemiology, phenotypic characteristics, and sites of detection, to put forth hypotheses on its possible origins. C. auris has not been detected in the natural environment; related species have been detected in in plants, insects, and aquatic environments, as well as from human body sites. It can tolerate hypersaline environments and higher temperatures than most Candida species. We explore hypotheses about the pre-emergence niche of C. auris, whether in the environmental or human microbiome, and speculate on factors that might have led to its spread, including the possible roles of healthcare, antifungal use, and environmental changes, including human activities that might have expanded its presence in the environment or caused increased human contact.}, }
@article {pmid31282802, year = {2018}, author = {Amsterdam, D and Ostrov, BE}, title = {The Impact of the Microbiome on Immunosenescence.}, journal = {Immunological investigations}, volume = {47}, number = {8}, pages = {801-811}, doi = {10.1080/08820139.2018.1537570}, pmid = {31282802}, issn = {1532-4311}, mesh = {Adaptive Immunity ; Aging/*immunology ; Animals ; Humans ; Immunity, Innate ; Microbiota/*immunology ; }, abstract = {Human microbiome investigations now provide evidence that changes in the microbiome over time and their interaction with the immune, endocrine, and nervous systems are associated with a wide array of disorders. Human immunological studies typically absent a microbiome consideration in their investigations. An area of recent exploration is the role of the microbiome as a critical partner in the development and function of the human immune system in aging. It is well known that immunologic maturation is influenced by a lifetime of interactions of the host with its companion microbiome. It is generally not well recognized that intestinal microbes play an essential role in the development and expansion of gut mucosal and systemic immune function. Gut microbial communities of elderly people have different composition and behavior compared to healthy younger adults. Comorbidities associated with microbial pathogens and an aberrant immune system tend to increase with aging. This review underscores the impact of the human-microbiome interface on the development and function of the immune system and on immunosenescence. These changes have important implications regarding health and health system utilization in the elderly population.}, }
@article {pmid31279340, year = {2019}, author = {Velsko, IM and Fellows Yates, JA and Aron, F and Hagan, RW and Frantz, LAF and Loe, L and Martinez, JBR and Chaves, E and Gosden, C and Larson, G and Warinner, C}, title = {Microbial differences between dental plaque and historic dental calculus are related to oral biofilm maturation stage.}, journal = {Microbiome}, volume = {7}, number = {1}, pages = {102}, pmid = {31279340}, issn = {2049-2618}, mesh = {Bacteria/*classification ; *Bacterial Physiological Phenomena ; Bacterial Proteins/genetics ; Biofilms/*growth &amp; development ; Bone and Bones/microbiology ; DNA, Ancient/analysis ; DNA, Bacterial/genetics ; Dental Calculus/history/*microbiology ; Dental Plaque/*microbiology ; Female ; History, Ancient ; Humans ; Male ; Metagenomics ; Microbiota/*physiology ; Periodontal Diseases/microbiology ; Proteomics ; Tooth/*microbiology ; }, abstract = {BACKGROUND: Dental calculus, calcified oral plaque biofilm, contains microbial and host biomolecules that can be used to study historic microbiome communities and host responses. Dental calculus does not typically accumulate as much today as historically, and clinical oral microbiome research studies focus primarily on living dental plaque biofilm. However, plaque and calculus reflect different conditions of the oral biofilm, and the differences in microbial characteristics between the sample types have not yet been systematically explored. Here, we compare the microbial profiles of modern dental plaque, modern dental calculus, and historic dental calculus to establish expected differences between these substrates.<br><br>RESULTS: Metagenomic data was generated from modern and historic calculus samples, and dental plaque metagenomic data was downloaded from the Human Microbiome Project. Microbial composition and functional profile were assessed. Metaproteomic data was obtained from a subset of historic calculus samples. Comparisons between microbial, protein, and metabolomic profiles revealed distinct taxonomic and metabolic functional profiles between plaque, modern calculus, and historic calculus, but not between calculus collected from healthy teeth and periodontal disease-affected teeth. Species co-exclusion was related to biofilm environment. Proteomic profiling revealed that healthy tooth samples contain low levels of bacterial virulence proteins and a robust innate immune response. Correlations between proteomic and metabolomic profiles suggest co-preservation of bacterial lipid membranes and membrane-associated proteins.<br><br>CONCLUSIONS: Overall, we find that there are systematic microbial differences between plaque and calculus related to biofilm physiology, and recognizing these differences is important for accurate data interpretation in studies comparing dental plaque and calculus.}, }
@article {pmid31278975, year = {2019}, author = {Soligo, M and Albini, M and Bertoli, FL and Marzano, V and Protto, V and Bracci-Laudiero, L and Minnone, G and De Benedetti, F and Chiaretti, A and Mantuano, E and Manni, L}, title = {Different responses of PC12 cells to different pro-nerve growth factor protein variants.}, journal = {Neurochemistry international}, volume = {129}, number = {}, pages = {104498}, doi = {10.1016/j.neuint.2019.104498}, pmid = {31278975}, issn = {1872-9754}, mesh = {Animals ; Cell Differentiation/drug effects ; Gene Expression Regulation/drug effects ; Male ; Mice ; Nerve Growth Factor/*pharmacology ; Nerve Growth Factors/biosynthesis/genetics ; Nerve Tissue Proteins ; PC12 Cells/*drug effects ; Protein Isoforms/pharmacology ; Protein Precursors/biosynthesis/genetics/*pharmacology ; Proteome ; RNA, Messenger/biosynthesis/genetics ; Rats ; Receptor, trkA/antagonists &amp; inhibitors ; Receptors, Growth Factor ; Receptors, Nerve Growth Factor/antagonists &amp; inhibitors ; Species Specificity ; }, abstract = {The present work aimed to explore the innovative hypothesis that different transcript/protein variants of a pro-neurotrophin may generate different biological outcomes in a cellular system. Nerve growth factor (NGF) is important in the development and progression of neurodegenerative and cancer conditions. Mature NGF (mNGF) originates from a precursor, proNGF, produced in mouse in two major variants, proNGF-A and proNGF-B. Different receptors bind mNGF and proNGF, generating neurotrophic or neurotoxic outcomes. It is known that dysregulation in the proNGF/mNGF ratio and in NGF-receptors expression affects brain homeostasis. To date, however, the specific roles of the two major proNGF variants remain unexplored. Here we attempted a first characterization of the possible differential effects of proNGF-A and proNGF-B on viability, differentiation and endogenous ngf gene expression in the PC12 cell line. We also investigated the differential involvement of NGF receptors in the actions of proNGF. We found that native mouse mNGF, proNGF-A and proNGF-B elicited different effects on PC12 cell survival and differentiation. Only mNGF and proNGF-A promoted neurotrophic responses when all NGF receptors are exposed at the cell surface. Tropomyosine receptor kinase A (TrkA) blockade inhibited cell differentiation, regardless of which NGF was added to culture media. Only proNGF-A exerted a pro-survival effect when TrkA was inhibited. Conversely, proNGF-B exerted differentiative effects when the p75 neurotrophin receptor (p75[NTR]) was antagonized. Stimulation with NGF variants differentially regulated the autocrine production of distinct proNgf mRNA. Overall, our findings suggest that mNGF and proNGF-A may elicit similar neurotrophic effects, not necessarily linked to activation of the same NGF-receptor, while the action of proNGF-B may be determined by the NGF-receptors balance. Thus, the proposed involvement of proNGF/NGF on the development and progression of neurodegenerative and tumor conditions may depend on the NGF-receptors balance, on specific NGF trancript expression and on the proNGF protein variant ratio.}, }
@article {pmid31277695, year = {2019}, author = {Ilves, M and Kinaret, PAS and Ndika, J and Karisola, P and Marwah, V and Fortino, V and Fedutik, Y and Correia, M and Ehrlich, N and Loeschner, K and Besinis, A and Vassallo, J and Handy, RD and Wolff, H and Savolainen, K and Greco, D and Alenius, H}, title = {Surface PEGylation suppresses pulmonary effects of CuO in allergen-induced lung inflammation.}, journal = {Particle and fibre toxicology}, volume = {16}, number = {1}, pages = {28}, pmid = {31277695}, issn = {1743-8977}, mesh = {Animals ; Copper/chemistry/*toxicity ; Female ; Gene Expression Profiling ; Genome-Wide Association Study ; Mice, Inbred BALB C ; Nanoparticles/chemistry/*toxicity ; Neutrophil Infiltration/*drug effects ; Ovalbumin/immunology ; Pneumonia/*chemically induced/genetics/immunology/pathology ; Polyethylene Glycols/*chemistry ; Surface Properties ; Transcriptome/*drug effects ; }, abstract = {BACKGROUND: Copper oxide (CuO) nanomaterials are used in a wide range of industrial and commercial applications. These materials can be hazardous, especially if they are inhaled. As a result, the pulmonary effects of CuO nanomaterials have been studied in healthy subjects but limited knowledge exists today about their effects on lungs with allergic airway inflammation (AAI). The objective of this study was to investigate how pristine CuO modulates allergic lung inflammation and whether surface modifications can influence its reactivity. CuO and its carboxylated (CuO COOH), methylaminated (CuO NH3) and PEGylated (CuO PEG) derivatives were administered here on four consecutive days via oropharyngeal aspiration in a mouse model of AAI. Standard genome-wide gene expression profiling as well as conventional histopathological and immunological methods were used to investigate the modulatory effects of the nanomaterials on both healthy and compromised immune system.<br><br>RESULTS: Our data demonstrates that although CuO materials did not considerably influence hallmarks of allergic airway inflammation, the materials exacerbated the existing lung inflammation by eliciting dramatic pulmonary neutrophilia. Transcriptomic analysis showed that CuO, CuO COOH and CuO NH3 commonly enriched neutrophil-related biological processes, especially in healthy mice. In sharp contrast, CuO PEG had a significantly lower potential in triggering changes in lungs of healthy and allergic mice revealing that surface PEGylation suppresses the effects triggered by the pristine material.<br><br>CONCLUSIONS: CuO as well as its functionalized forms worsen allergic airway inflammation by causing neutrophilia in the lungs, however, our results also show that surface PEGylation can be a promising approach for inhibiting the effects of pristine CuO. Our study provides information for health and safety assessment of modified CuO materials, and it can be useful in the development of nanomedical applications.}, }
@article {pmid31275260, year = {2019}, author = {Rodionov, DA and Arzamasov, AA and Khoroshkin, MS and Iablokov, SN and Leyn, SA and Peterson, SN and Novichkov, PS and Osterman, AL}, title = {Micronutrient Requirements and Sharing Capabilities of the Human Gut Microbiome.}, journal = {Frontiers in microbiology}, volume = {10}, number = {}, pages = {1316}, pmid = {31275260}, issn = {1664-302X}, support = {R01 DK030292/DK/NIDDK NIH HHS/United States ; R01 GM108527/GM/NIGMS NIH HHS/United States ; }, abstract = {The human gut microbiome harbors a diverse array of metabolic pathways contributing to its development and homeostasis via a complex web of diet-dependent metabolic interactions within the microbial community and host. Genomics-based reconstruction and predictive modeling of these interactions would provide a framework for diagnostics and treatment of dysbiosis-related syndromes via rational selection of therapeutic prebiotics and dietary nutrients. Of particular interest are micronutrients, such as B-group vitamins, precursors of indispensable metabolic cofactors, that are produced de novo by some gut bacteria (prototrophs) but must be provided exogenously in the diet for many other bacterial species (auxotrophs) as well as for the mammalian host. Cross-feeding of B vitamins between prototrophic and auxotrophic species is expected to strongly contribute to the homeostasis of microbial communities in the distal gut given the efficient absorption of dietary vitamins in the upper gastrointestinal tract. To confidently estimate the balance of microbiome micronutrient biosynthetic capabilities and requirements using available genomic data, we have performed a subsystems-based reconstruction of biogenesis, salvage and uptake for eight B vitamins (B1, B2, B3, B5, B6, B7, B9, and B12) and queuosine (essential factor in tRNA modification) over a reference set of 2,228 bacterial genomes representing 690 cultured species of the human gastrointestinal microbiota. This allowed us to classify the studied organisms with respect to their pathway variants and infer their prototrophic vs. auxotrophic phenotypes. In addition to canonical vitamin pathways, several conserved partial pathways were identified pointing to alternative routes of syntrophic metabolism and expanding a microbial vitamin "menu" by several pathway intermediates (vitamers) such as thiazole, quinolinate, dethiobiotin, pantoate. A cross-species comparison was applied to assess the extent of conservation of vitamin phenotypes at distinct taxonomic levels (from strains to families). The obtained reference collection combined with 16S rRNA gene-based phylogenetic profiles was used to deduce phenotype profiles of the human gut microbiota across in two large cohorts. This analysis provided the first estimate of B-vitamin requirements, production and sharing capabilities in the human gut microbiome establishing predictive phenotype profiling as a new approach to classification of microbiome samples. Future expansion of our reference genomic collection of metabolic phenotypes will allow further improvement in coverage and accuracy of predictive phenotype profiling of the human microbiome.}, }
@article {pmid31264406, year = {2019}, author = {Claassens, NJ and Finger-Bou, M and Scholten, B and Muis, F and de Groot, JJ and de Gier, JW and de Vos, WM and van der Oost, J}, title = {Bicistronic Design-Based Continuous and High-Level Membrane Protein Production in Escherichia coli.}, journal = {ACS synthetic biology}, volume = {8}, number = {7}, pages = {1685-1690}, pmid = {31264406}, issn = {2161-5063}, mesh = {Escherichia coli/*genetics ; Escherichia coli Proteins/*genetics ; Gene Expression/genetics ; Gene Expression Regulation, Bacterial/genetics ; Genetic Vectors/genetics ; Membrane Proteins/*genetics ; Promoter Regions, Genetic/genetics ; }, abstract = {Escherichia coli has been widely used as a platform microorganism for both membrane protein production and cell factory engineering. The current methods to produce membrane proteins in this organism require the induction of target gene expression and often result in unstable, low yields. Here, we present a method combining a constitutive promoter with a library of bicistronic design (BCD) elements, which enables inducer-free, tuned translation initiation for optimal protein production. Our system mediates stable, constitutive production of bacterial membrane proteins at yields that outperform those obtained with E. coli Lemo21(DE3), the current gold standard for bacterial membrane protein production. We envisage that the continuous, fine-tunable, and high-level production of membrane proteins by our method will greatly facilitate their study and their utilization in engineering cell factories.}, }
@article {pmid31263750, year = {2019}, author = {Katsnelson, A}, title = {Standards Seekers Put the Human Microbiome in Their Sights.}, journal = {ACS central science}, volume = {5}, number = {6}, pages = {929-932}, doi = {10.1021/acscentsci.9b00557}, pmid = {31263750}, issn = {2374-7943}, }
@article {pmid31263284, year = {2019}, author = {Depommier, C and Everard, A and Druart, C and Plovier, H and Van Hul, M and Vieira-Silva, S and Falony, G and Raes, J and Maiter, D and Delzenne, NM and de Barsy, M and Loumaye, A and Hermans, MP and Thissen, JP and de Vos, WM and Cani, PD}, title = {Supplementation with Akkermansia muciniphila in overweight and obese human volunteers: a proof-of-concept exploratory study.}, journal = {Nature medicine}, volume = {25}, number = {7}, pages = {1096-1103}, pmid = {31263284}, issn = {1546-170X}, support = {336452/ERC_/European Research Council/International ; }, mesh = {Adult ; Aged ; *Dietary Supplements ; Double-Blind Method ; Feces/microbiology ; Gastrointestinal Microbiome ; Humans ; Insulin Resistance ; Middle Aged ; Obesity/*diet therapy/metabolism/microbiology ; Overweight/*diet therapy/metabolism/microbiology ; Pilot Projects ; *Verrucomicrobia ; }, abstract = {Metabolic syndrome is characterized by a constellation of comorbidities that predispose individuals to an increased risk of developing cardiovascular pathologies as well as type 2 diabetes mellitus[1]. The gut microbiota is a new key contributor involved in the onset of obesity-related disorders[2]. In humans, studies have provided evidence for a negative correlation between Akkermansia muciniphila abundance and overweight, obesity, untreated type 2 diabetes mellitus or hypertension[3-8]. Since the administration of A. muciniphila has never been investigated in humans, we conducted a randomized, double-blind, placebo-controlled pilot study in overweight/obese insulin-resistant volunteers; 40 were enrolled and 32 completed the trial. The primary end points were safety, tolerability and metabolic parameters (that is, insulin resistance, circulating lipids, visceral adiposity and body mass). Secondary outcomes were gut barrier function (that is, plasma lipopolysaccharides) and gut microbiota composition. In this single-center study, we demonstrated that daily oral supplementation of 10[10] A. muciniphila bacteria either live or pasteurized for three months was safe and well tolerated. Compared to placebo, pasteurized A. muciniphila improved insulin sensitivity (+28.62 ± 7.02%, P = 0.002), and reduced insulinemia (-34.08 ± 7.12%, P = 0.006) and plasma total cholesterol (-8.68 ± 2.38%, P = 0.02). Pasteurized A. muciniphila supplementation slightly decreased body weight (-2.27 ± 0.92 kg, P = 0.091) compared to the placebo group, and fat mass (-1.37 ± 0.82 kg, P = 0.092) and hip circumference (-2.63 ± 1.14 cm, P = 0.091) compared to baseline. After three months of supplementation, A. muciniphila reduced the levels of the relevant blood markers for liver dysfunction and inflammation while the overall gut microbiome structure was unaffected. In conclusion, this proof-of-concept study (clinical trial no. NCT02637115) shows that the intervention was safe and well tolerated and that supplementation with A. muciniphila improves several metabolic parameters.}, }
@article {pmid31262073, year = {2019}, author = {Tavakoli, A and Flanagan, JL}, title = {The Case for a More Holistic Approach to Dry Eye Disease: Is It Time to Move beyond Antibiotics?.}, journal = {Antibiotics (Basel, Switzerland)}, volume = {8}, number = {3}, pages = {}, pmid = {31262073}, issn = {2079-6382}, abstract = {Dry eye disease (DED) is one of the most frequent presentations to optometrists with over 16 million US adults (6.8% of adult population) diagnosed as having this disorder. The majority of associated marketed products offer relief from symptomatology but do not address aetiology. DED harbours many distinguishing features of a chronic inflammatory disorder. The recent explosion in human microbiome research has sparked interest in the ocular microbiome and its role in the preservation and extension of ocular surface health and in the contribution of the gut microbiome to chronic systemic inflammation and associated "Western life-style" diseases. With a significant lack of success for many patients using currently available DED treatments, in this era of the microbiome, we are interested in exploring potential novel therapies that aim to reconstitute healthy bacterial communities both locally and distally (in the gut) as a treatment for DED. Although this direction of investigation is in its infancy, burgeoning interest makes such a review timely. This paper considers a number of studies into the use functional foods and associated products to ameliorate dry eye.}, }
@article {pmid31261078, year = {2019}, author = {Valentine, G and Prince, A and Aagaard, KM}, title = {The Neonatal Microbiome and Metagenomics: What Do We Know and What Is the Future?.}, journal = {NeoReviews}, volume = {20}, number = {5}, pages = {e258-e271}, doi = {10.1542/neo.20-5-e258}, pmid = {31261078}, issn = {1526-9906}, mesh = {Female ; Forecasting ; Humans ; Infant Health/*trends ; Infant, Newborn ; Metagenome/*physiology ; Metagenomics/methods/*trends ; Microbiota/*physiology ; Pregnancy ; }, abstract = {The human microbiota includes the trillions of microorganisms living in the human body whereas the human microbiome includes the genes and gene products of this microbiota. Bacteria were historically largely considered to be pathogens that inevitably led to human disease. However, because of advances in both cultivation-based methods and the advent of metagenomics, bacteria are now recognized to be largely beneficial commensal organisms and thus, key to normal and healthy human development. This relatively new area of medical research has elucidated insights into diseases such as inflammatory bowel disease and obesity, as well as metabolic and atopic disorders. However, much remains unknown about the complexity of microbe-microbe and microbe-host interactions. Future efforts aimed at answering key questions pertaining to the early establishment of the microbiome, alongside what defines its dysbiosis, will likely lead to long-term health and mitigation of disease. Here, we review the relevant literature pertaining to modulations in the perinatal and neonatal microbiome, the impact of environmental and maternal factors in shaping the neonatal microbiome, and future questions and directions in the exciting emerging arena of metagenomic medicine.}, }
@article {pmid31253623, year = {2019}, author = {Korpela, K and Dikareva, E and Hanski, E and Kolho, KL and de Vos, WM and Salonen, A}, title = {Cohort profile: Finnish Health and Early Life Microbiota (HELMi) longitudinal birth cohort.}, journal = {BMJ open}, volume = {9}, number = {6}, pages = {e028500}, pmid = {31253623}, issn = {2044-6055}, mesh = {Adult ; Breast Feeding ; Cohort Studies ; Female ; Finland ; Gastrointestinal Microbiome/*physiology ; Humans ; Infant ; Infant, Newborn ; Longitudinal Studies ; Male ; Pregnancy ; Prospective Studies ; }, abstract = {PURPOSE: HELMi (Health and Early Life Microbiota) is a longitudinal, prospective general population birth cohort, set up to identify environmental, lifestyle and genetic factors that modify the intestinal microbiota development in the first years of life and their relation to child health and well-being.<br><br>PARTICIPANTS: The HELMi cohort consists of 1055 healthy term infants born in 2016-2018 mainly at the capital region of Finland and their parents. The intestinal microbiota development of the infants is characterised based on nine, strategically selected, faecal samples and connected to extensive online questionnaire-collected metadata at weekly to monthly intervals focusing on the diet, other exposures and family's lifestyle as well as the health and growth of the child. Motor and cognitive developmental screening takes place at 18 months. Infant's DNA sample, mother's breast milk sample and both parent's spot faecal samples have been collected.<br><br>FINDINGS TO DATE: The mean age of the mothers was 32.8 (SD 4.1) and fathers/coparents 34.8 (5.3) years at the time of enrolment. Seventeen percentage (n=180) of the infants were born by caesarean section. Just under half (49%) were firstborns; 50.7% were males. At 3 months of age, 86% of the babies were exclusively breastfed and 2% exclusively formula-fed.<br><br>FUTURE PLANS: The current follow-up from pregnancy to first 24 months will be completed in March 2020, totalling to over 10&#x2009;000 biological samples and over 50&#x2009;000 questionnaire entries. The results are expected to identify environmental and host factors that affect early gut microbiota development and health, and hence give indications of how to prevent or reverse microbiota perturbations in infancy. This prospective cohort will be followed up further to identify how the early microbiota relates to later health outcomes, especially weight gain, infections and allergic and other chronic diseases.<br><br>TRIAL REGISTRATION NUMBER: NCT03996304; Pre-results.}, }
@article {pmid31253198, year = {2019}, author = {Lokugamage, AU and Pathberiya, SDC}, title = {The microbiome seeding debate - let's frame it around women-centred care.}, journal = {Reproductive health}, volume = {16}, number = {1}, pages = {91}, pmid = {31253198}, issn = {1742-4755}, mesh = {Cesarean Section/*standards ; Female ; Humans ; Infant, Newborn ; *Microbiota ; Patient-Centered Care/*standards ; Pregnancy ; Vagina/*microbiology ; }, abstract = {UNLABELLED: In a global culture that is increasingly interested in ecological interventions, probiotics, 'friendly bacteria', microbiome preservation/restoration and long-term health, there is growing awareness of the idea of seeding the vaginal microbiome in the new born after caesarean section. It is postulated as a way of restoring helpful missing microbes and preventing long term non-communicable diseases of babies delivered by caesarean section. Currently, there is a deluge of evidence being published on the human microbiome, which can be challenging to digest and absorb by scientists, clinicians and patients. The specific evidence base around this technique is at its early stages. This commentary discusses what advice is currently available from a feminist and a person-centred care perspective.<br><br>ABSTRAKT: Det er en voksende interesse internasjonalt for &#xf8;kologiske intervensjoner, probiotika, 'snille bakterier', bevaring/gjenoppretting av. mikrobiomet og helse i et langtidsperspektiv. I denne sammenhengen er det en &#xf8;kende interesse for tanken om &#xe5; s&#xe5; det vaginale mikrobiomet (vaginal seeding) p&#xe5; den nyf&#xf8;dte etter et keisersnitt. Dette er postulert som en m&#xe5;te &#xe5; gjenopprette manglende normalflora/mikrobiom og forebygge langvarige ikke-smittsomme sykdommer hos barn f&#xf8;dt med keisersnitt. For tiden publiseres det mye forskning om menneskets mikrobiom, noe som kan v&#xe6;re utfordrende &#xe5; ford&#xf8;ye og ta til seg for forskere, klinikere og pasienter. Forskningen p&#xe5; denne spesifikke metoden er i sin begynnelse. Denne kommentaren dr&#xf8;fter hvilke r&#xe5;d som for &#xf8;yeblikket er tilgjengelige, fra et feministisk og personsentrert omsorgsperspektiv. POPULARISERT SAMMENDRAG P&#xe5; NORSK: Det menneskelige mikrobiomet er summen av alle bakteriene som dekker den menneskelige kroppen og det hjelper kroppen i &#xe5; fungere optimalt. N&#xe5;r mikrobiomet forstyrres, vil kroppen kunne f&#xe5; betennelsesreaksjoner og allergier. I f&#xf8;dsel finnes de &#xab;gode&#xbb; bakteriene i kvinnens vagina. (det vaginale mikrobiomet) som man tror vil v&#xe6;re fordelaktig for babyens evne til &#xe5; utvikle et sunt immunsystem. Babyer som er f&#xf8;dt med keisersnitt vil ikke bli eksponert for disse &#xab;gode&#xbb; bakteriene og det kan p&#xe5;virke barnets immunforsvar negativt og potensielt &#xf8;ke sjansen for allergier og betennelsesreaksjoner i kroppen p&#xe5; lang sikt. Vaginal seeding (et fors&#xf8;k p&#xe5; &#xe5; gjenopprette balansen og noen av de gode bakterier i spedbarnet gjennom &#xe5; tilf&#xf8;re mors vaginale bakterier via en kompress som strykes over spedbarnets ansikt) Vaginal seeding er en metode som noen forskere sier muligens delvis gjenoppretter de manglende &#xab;gode&#xbb; bakteriene etter et keisersnitt. Forskningen er p&#xe5; et tidlig stadium. Det har v&#xe6;rt avisartikler og en film om emnet og m&#xf8;dre har funnet ut om vaginal seeding som en m&#xe5;te &#xe5; gjenopprette denne delen av babyens mikrobiom. Foreldre &#xf8;nsker &#xe5; diskutere vaginal seeding, men p&#xe5; n&#xe5;v&#xe6;rende tidspunkt er helsevesenet avventende og helsepersonell er ikke godt nok informert. Denne artikkelen vil se p&#xe5; den p&#xe5;g&#xe5;ende diskusjonen. R&#xe9;SUM&#xe9;: Dans une culture mondiale qui s'int&#xe9;resse de plus en plus aux interventions &#xe9;cologiques, aux probiotiques, aux &#xab;bact&#xe9;ries amicales&#xbb;, &#xe0; la pr&#xe9;servation / restauration du microbiome et &#xe0; la sant&#xe9; &#xe0; long terme, on commence &#xe0; prendre conscience de l'id&#xe9;e d'ensemencer le microbiome vaginal chez le nouveau-n&#xe9; apr&#xe8;s une c&#xe9;sarienne. Il est postul&#xe9; comme un moyen de restaurer les microbes manquants et d'aider &#xe0; pr&#xe9;venir les maladies non transmissibles &#xe0; long terme des b&#xe9;b&#xe9;s mis au monde par c&#xe9;sarienne. Il existe actuellement un d&#xe9;luge de preuves sur le microbiome humain, qui peuvent &#xea;tre difficiles &#xe0; dig&#xe9;rer et &#xe0; absorber par les scientifiques, les cliniciens et les patients. La base de preuves sp&#xe9;cifique autour de cette technique en est &#xe0; ses d&#xe9;buts. Ce commentaire discute des conseils actuellement disponibles dans une perspective de soins f&#xe9;ministe et centr&#xe9;e sur la personne. R&#xe9;SUM&#xe9; SIMPLIFI&#xe9;: Le microbiome humain est constitu&#xe9; de tous les microbes qui recouvrent le corps humain et qui aident le corps &#xe0; bien fonctionner. Lorsque le microbiome est perturb&#xe9;, le corps devient plus inflammatoire et est sujet aux allergies. Lors de l'accouchement, le vagin d'une m&#xe8;re (le microbiome vaginal) contient des "bact&#xe9;ries amicales" qui pourraient &#xea;tre b&#xe9;n&#xe9;fiques pour l'enfant et aider le b&#xe9;b&#xe9; &#xe0; d&#xe9;velopper un syst&#xe8;me immunitaire en bonne sant&#xe9;. Les b&#xe9;b&#xe9;s n&#xe9;s par c&#xe9;sarienne ne sont g&#xe9;n&#xe9;ralement pas expos&#xe9;s &#xe0; ces &#xab;bact&#xe9;ries b&#xe9;n&#xe9;fiques&#xbb;, ce qui pourrait affecter n&#xe9;gativement le syst&#xe8;me immunitaire du b&#xe9;b&#xe9; et potentiellement augmenter le risque d'allergies et d'inflammation &#xe0; long terme. Selon certains scientifiques, l'ensemencement vaginal pourrait partiellement restaurer les &#xab;bact&#xe9;ries amies&#xbb; manquantes apr&#xe8;s la c&#xe9;sarienne. La recherche en est &#xe0; ses d&#xe9;buts. Il y a eu des articles de journaux et un film &#xe0; ce sujet, et les m&#xe8;res ont d&#xe9;couvert l'existence d'un ensemencement vaginal (o&#xf9; une compresse plac&#xe9;e dans le vagin de la m&#xe8;re pourrait &#xea;tre appliqu&#xe9;e sur l'enfant apr&#xe8;s la c&#xe9;sarienne) afin de restaurer une partie du microbiome du b&#xe9;b&#xe9;. Les parents souhaitent discuter de l'ensemencement vaginal, mais &#xe0; l'heure actuelle, les organisations m&#xe9;dicales sont prudentes et les praticiens ne sont pas suffisamment inform&#xe9;s. Cet article examine le d&#xe9;bat en cours.<br><br>RESUMO: Numa cultura global que est&#xe1; cada vez mais interessada em interven&#xe7;&#xf5;es ecol&#xf3;gicas, probi&#xf3;ticos, "bact&#xe9;rias amig&#xe1;veis", preserva&#xe7;&#xe3;o/restaura&#xe7;&#xe3;o do microbioma e sa&#xfa;de a longo prazo, h&#xe1; uma crescente consci&#xea;ncia sobre a ideia de semear o microbioma vaginal no rec&#xe9;m-nascido ap&#xf3;s uma cirurgia cesariana. Isso est&#xe1; sendo postulado como uma forma de restaurar micr&#xf3;bios &#xfa;teis que lhe faltariam e prevenir doen&#xe7;as n&#xe3;o transmiss&#xed;veis em longo prazo para beb&#xea;s que nasceram pela via cir&#xfa;rgica. Atualmente, h&#xe1; um aumento massivo de evid&#xea;ncias sendo publicadas sobre o microbioma humano cuja absor&#xe7;&#xe3;o e digest&#xe3;o pode ser desafiadora para cientistas, cl&#xed;nicos e pacientes. A base espec&#xed;fica da evid&#xea;ncia que cerca essa t&#xe9;cnica ainda est&#xe1; em est&#xe1;gios preliminares. Este coment&#xe1;rio discute o aconselhamento atualmente dispon&#xed;vel numa perspectiva feminista e centrada na pessoa. S&#xed;NTESE SIMPLIFICADA: O microbioma humano est&#xe1; composto por todos os micr&#xf3;bios que cobrem o corpo humano e que ajudam o corpo a funcionar bem. Quando o microbioma &#xe9; perturbado, o corpo tem mais inflama&#xe7;&#xf5;es e maior propens&#xe3;o a desenvolver alergias. Ao nascimento, h&#xe1; "bact&#xe9;rias amig&#xe1;veis" na vagina materna (o microbioma vaginal) que podem ser ben&#xe9;ficas &#xe0; crian&#xe7;a e ajudar o beb&#xea; a desenvolver um sistema imunol&#xf3;gico saud&#xe1;vel. Beb&#xea;s que nascem por cesariana usualmente n&#xe3;o s&#xe3;o expostos a essas "bact&#xe9;rias amig&#xe1;veis" e isso poder&#xe1; afetar negativamente o sistema imunol&#xf3;gico do beb&#xea;, aumentando potencialmente a probabilidade de alegrias e inflama&#xe7;&#xf5;es no longo prazo. A semeadura de bact&#xe9;ria vaginais &#xe9; um m&#xe9;todo que alguns cientistas afirmam que poder&#xe1; restaurar parcialmente as "bact&#xe9;rias amig&#xe1;veis" faltantes depois de uma cesariana. Essa pesquisa est&#xe1; em fase preliminar. Houve alguns artigos em jornais e um filme sobre isso, e as m&#xe3;es descobriram a possibilidade da semeadura vaginal (quando &#xe9; feito um swab da vagina materna que &#xe9; esfregado no beb&#xea; ap&#xf3;s a ces&#xe1;rea) para restaurar parte do microbioma do beb&#xea;. Pais desejam discutir a semeadura vaginal, mas, no momento, as organiza&#xe7;&#xf5;es m&#xe9;dicas t&#xea;m sido cautelosas e os profissionais n&#xe3;o est&#xe3;o adequadamente informados. Este artigo aborda o debate em andamento.<br><br>RESUMEN: En una cultura global que est&#xe1; cada vez m&#xe1;s interesada en las intervenciones ecol&#xf3;gicas, los probi&#xf3;ticos, las "bacterias amigables", la conservaci&#xf3;n/restauraci&#xf3;n de microbiomas y la salud a largo plazo, hay una creciente conciencia de la idea de sembrar el microbioma vaginal en el reci&#xe9;n nacido despu&#xe9;s de la ces&#xe1;rea. Se postula como una forma de restaurar los microbios &#xfa;tiles faltantes y prevenir las enfermedades no transmisibles a largo plazo de los beb&#xe9;s nacidos por ces&#xe1;rea. Actualmente, se est&#xe1; publicando una gran cantidad de pruebas sobre el microbioma humano, que pueden ser dif&#xed;ciles de digerir y absorber por parte de cient&#xed;ficos, cl&#xed;nicos y pacientes. La base de la evidencia espec&#xed;fica en torno a esta t&#xe9;cnica se encuentra en sus primeras etapas. Este art&#xed;culo analiza qu&#xe9; consejos est&#xe1;n disponibles actualmente desde una perspectiva feminista y de atenci&#xf3;n centrada en la persona.<br><br>RESUMEN EN LENGUAJE SENCILLO: El microbioma humano est&#xe1; hecho de todos las bacterias que cubren el cuerpo humano y que ayudan al cuerpo a funcionar bien. Cuando se altera el microbioma, el cuerpo se inflama m&#xe1;s y es propenso a las alergias. En el parto, hay "bacterias amigables" en la vagina de la madre (el microbioma vaginal) que podr&#xed;an ser beneficiosas para el ni&#xf1;o y ayudar al beb&#xe9; a desarrollar un sistema inmunol&#xf3;gico saludable. Los beb&#xe9;s que nacen por ces&#xe1;rea generalmente no se exponen a estas "bacterias amigables" y esto podr&#xed;a afectar negativamente el sistema inmunol&#xf3;gico del beb&#xe9;, lo que podr&#xed;a aumentar la probabilidad de alergias e inflamaci&#xf3;n a largo plazo. La siembra vaginal es un m&#xe9;todo que algunos cient&#xed;ficos dicen que podr&#xed;a restaurar parcialmente las "bacterias amigables" que faltan despu&#xe9;s de la ces&#xe1;rea. La investigaci&#xf3;n se encuentra en sus primeras etapas. Han habido art&#xed;culos period&#xed;sticos y una pel&#xed;cula sobre esto, y las madres se han enterado de la siembra vaginal (donde se puede frotar el ni&#xf1;o con una torunda de la vagina de la madre despu&#xe9;s de la ces&#xe1;rea) para restaurar la parte del microbioma del beb&#xe9;. Los padres quieren hablar sobre la siembra vaginal, pero en la actualidad las organizaciones m&#xe9;dicas son cautelosas y los profesionales no est&#xe1;n informados adecuadamente. Este art&#xed;culo analiza el debate en curso.}, }
@article {pmid31246421, year = {2019}, author = {Gumkowski, JD and Martinie, RJ and Corrigan, PS and Pan, J and Bauerle, MR and Almarei, M and Booker, SJ and Silakov, A and Krebs, C and Boal, AK}, title = {Analysis of RNA Methylation by Phylogenetically Diverse Cfr Radical S-Adenosylmethionine Enzymes Reveals an Iron-Binding Accessory Domain in a Clostridial Enzyme.}, journal = {Biochemistry}, volume = {58}, number = {29}, pages = {3169-3184}, pmid = {31246421}, issn = {1520-4995}, support = {R00 GM100011/GM/NIGMS NIH HHS/United States ; R35 GM119707/GM/NIGMS NIH HHS/United States ; R35 GM122595/GM/NIGMS NIH HHS/United States ; }, mesh = {Amino Acid Sequence ; Clostridioides difficile/genetics/*metabolism ; Iron/*metabolism ; Methylation ; *Phylogeny ; Protein Binding/physiology ; RNA/genetics/*metabolism ; S-Adenosylmethionine/*metabolism ; }, abstract = {Cfr is a radical S-adenosylmethionine (SAM) RNA methylase linked to multidrug antibiotic resistance in bacterial pathogens. It catalyzes a chemically challenging C-C bond-forming reaction to methylate C8 of A2503 (Escherichia coli numbering) of 23S rRNA during ribosome assembly. The cfr gene has been identified as a mobile genetic element in diverse bacteria and in the genome of select Bacillales and Clostridiales species. Despite the importance of Cfr, few representatives have been purified and characterized in vitro. Here we show that Cfr homologues from Bacillus amyloliquefaciens, Enterococcus faecalis, Paenibacillus lautus, and Clostridioides difficile act as C8 adenine RNA methylases in biochemical assays. C. difficile Cfr contains an additional Cys-rich C-terminal domain that binds a mononuclear Fe[2+] ion in a rubredoxin-type Cys4 motif. The C-terminal domain can be truncated with minimal impact on C. difficile Cfr activity, but the rate of turnover is decreased upon disruption of the Fe[2+]-binding site by Zn[2+] substitution or ligand mutation. These findings indicate an important purpose for the observed C-terminal iron in the native fusion protein. Bioinformatic analysis of the C. difficile Cfr Cys-rich domain shows that it is widespread (∼1400 homologues) as a stand-alone gene in pathogenic or commensal Bacilli and Clostridia, with >10% encoded adjacent to a predicted radical SAM RNA methylase. Although the domain is not essential for in vitro C. difficile Cfr activity, the genomic co-occurrence and high abundance in the human microbiome suggest a possible functional role for a specialized rubredoxin in certain radical SAM RNA methylases that are relevant to human health.}, }
@article {pmid31231350, year = {2019}, author = {Savijoki, K and Nyman, TA and Kainulainen, V and Miettinen, I and Siljamäki, P and Fallarero, A and Sandholm, J and Satokari, R and Varmanen, P}, title = {Growth Mode and Carbon Source Impact the Surfaceome Dynamics of Lactobacillus rhamnosus GG.}, journal = {Frontiers in microbiology}, volume = {10}, number = {}, pages = {1272}, pmid = {31231350}, issn = {1664-302X}, abstract = {Bacterial biofilms have clear implications in disease and in food applications involving probiotics. Here, we show that switching the carbohydrate source from glucose to fructose increased the biofilm formation and the total surface-antigenicity of a well-known probiotic, Lactobacillus rhamnosus GG. Surfaceomes (all cell surface-associated proteins) of GG cells grown with glucose and fructose in planktonic and biofilm cultures were identified and compared, which indicated carbohydrate source-dependent variations, especially during biofilm growth. The most distinctive differences under these conditions were detected with several surface adhesins (e.g., MBF, SpaC pilus protein and penicillin-binding proteins), enzymes (glycoside hydrolases, PrsA, PrtP, PrtR, and HtrA) and moonlighting proteins (glycolytic, transcription/translation and stress-associated proteins, r-proteins, tRNA synthetases, Clp family proteins, PepC, PepN, and PepA). The abundance of several known adhesins and candidate moonlighters, including enzymes acting on casein-derived peptides (ClpP, PepC, and PepN), increased in the biofilm cells grown on fructose, from which the surface-associated aminopeptidase activity mediated by PepC and PepN was further confirmed by an enzymatic assay. The mucus binding factor (MBF) was found most abundant in fructose grown biofilm cells whereas SpaC adhesin was identified specifically from planktonic cells growing on fructose. An additional indirect ELISA indicated both growth mode- and carbohydrate-dependent differences in abundance of SpaC, whereas the overall adherence of GG assessed with porcine mucus indicated that the carbon source and the growth mode affected mucus adhesion. The adherence of GG cells to mucus was almost completely inhibited by anti-SpaC antibodies regardless of growth mode and/or carbohydrate source, indicating the key role of the SpaCBA pilus in adherence under the tested conditions. Altogether, our results suggest that carbon source and growth mode coordinate mechanisms shaping the proteinaceous composition of GG cell surface, which potentially contributes to resistance, nutrient acquisition and cell-cell interactions under different conditions. In conclusion, the present study shows that different growth regimes and conditions can have a profound impact on the adherent and antigenic features of GG, thereby providing new information on how to gain additional benefits from this probiotic.}, }
@article {pmid31231319, year = {2019}, author = {Stinson, LF and Boyce, MC and Payne, MS and Keelan, JA}, title = {The Not-so-Sterile Womb: Evidence That the Human Fetus Is Exposed to Bacteria Prior to Birth.}, journal = {Frontiers in microbiology}, volume = {10}, number = {}, pages = {1124}, pmid = {31231319}, issn = {1664-302X}, abstract = {The human microbiome includes trillions of bacteria, many of which play a vital role in host physiology. Numerous studies have now detected bacterial DNA in first-pass meconium and amniotic fluid samples, suggesting that the human microbiome may commence in utero. However, these data have remained contentious due to underlying contamination issues. Here, we have used a previously described method for reducing contamination in microbiome workflows to determine if there is a fetal bacterial microbiome beyond the level of background contamination. We recruited 50 women undergoing non-emergency cesarean section deliveries with no evidence of intra-uterine infection and collected first-pass meconium and amniotic fluid samples. Full-length 16S rRNA gene sequencing was performed using PacBio SMRT cell technology, to allow high resolution profiling of the fetal gut and amniotic fluid bacterial microbiomes. Levels of inflammatory cytokines were measured in amniotic fluid, and levels of immunomodulatory short chain fatty acids (SCFAs) were quantified in meconium. All meconium samples and most amniotic fluid samples (36/43) contained bacterial DNA. The meconium microbiome was dominated by reads that mapped to Pelomonas puraquae. Aside from this species, the meconium microbiome was remarkably heterogeneous between patients. The amniotic fluid microbiome was more diverse and contained mainly reads that mapped to typical skin commensals, including Propionibacterium acnes and Staphylococcus spp. All meconium samples contained acetate and propionate, at ratios similar to those previously reported in infants. P. puraquae reads were inversely correlated with meconium propionate levels. Amniotic fluid cytokine levels were associated with the amniotic fluid microbiome. Our results demonstrate that bacterial DNA and SCFAs are present in utero, and have the potential to influence the developing fetal immune system.}, }
@article {pmid31220972, year = {2019}, author = {Koontz, JM and Dancy, BCR and Horton, CL and Stallings, JD and DiVito, VT and Lewis, JA}, title = {The Role of the Human Microbiome in Chemical Toxicity.}, journal = {International journal of toxicology}, volume = {38}, number = {4}, pages = {251-264}, doi = {10.1177/1091581819849833}, pmid = {31220972}, issn = {1092-874X}, mesh = {Animals ; Hazardous Substances/*toxicity ; Humans ; Microbiota/*drug effects ; }, abstract = {There is overwhelming evidence that the microbiome must be considered when evaluating the toxicity of chemicals. Disruption of the normal microbial flora is a known effect of toxic exposure, and these disruptions may lead to human health effects. In addition, the biotransformation of numerous compounds has been shown to be dependent on microbial enzymes, with the potential for different host health outcomes resulting from variations in the microbiome. Evidence suggests that such metabolism of environmental chemicals by enzymes from the host's microbiota can affect the toxicity of that chemical to the host. Chemical-microbial interactions can be categorized into two classes: Microbiome Modulation of Toxicity (MMT) and Toxicant Modulation of the Microbiome (TMM). MMT refers to transformation of a chemical by microbial enzymes or metabolites to modify the chemical in a way that makes it more or less toxic. TMM is a change in the microbiota that results from a chemical exposure. These changes span a large magnitude of effects and may vary from microbial gene regulation, to inhibition of a specific enzyme, to the death of the microbes. Certain microbiomes or microbiota may become associated with different health outcomes, such as resistance or susceptibility to exposure to certain toxic chemicals, the ability to recover following a chemical-induced injury, the presence of disease-associated phenotypes, and the effectiveness of immune responses. Future work in toxicology will require an understanding of how the microbiome interacts with toxicants to fully elucidate how a compound will affect a diverse, real-world population.}, }
@article {pmid31220751, year = {2019}, author = {Zhang, YJ and Hu, HW and Chen, QL and Singh, BK and Yan, H and Chen, D and He, JZ}, title = {Transfer of antibiotic resistance from manure-amended soils to vegetable microbiomes.}, journal = {Environment international}, volume = {130}, number = {}, pages = {104912}, doi = {10.1016/j.envint.2019.104912}, pmid = {31220751}, issn = {1873-6750}, mesh = {Anti-Bacterial Agents/*pharmacology ; Bacteria/drug effects/*genetics/isolation &amp; purification ; *Drug Resistance, Microbial/genetics ; High-Throughput Nucleotide Sequencing ; Lactuca/*microbiology ; Manure/*analysis ; *Microbiota ; Real-Time Polymerase Chain Reaction ; Soil/chemistry ; *Soil Microbiology ; Victoria ; }, abstract = {The increasing antimicrobial resistance in manure-amended soil can potentially enter food chain, representing an important vehicle for antibiotic resistance genes (ARGs) transmission into human microbiome. However, the pathways for transmission of ARGs from soil to plant remain unclear. Here, we explored the impacts of poultry and cattle manure application on the patterns of resistome in soil and lettuce microbiome including rhizosphere, root endosphere, leaf endosphere and phyllosphere, to identify the potential transmission routes of ARGs in the soil-plant system. After 90 days of cultivation, a total of 144 ARGs were detected in all samples using high-throughput quantitative PCR. Rhizosphere soil samples harbored the most diverse ARGs compared with other components of lettuce. Cattle manure application increased the abundance of ARGs in root endophyte, while poultry manure application increased ARGs in rhizosphere, root endophyte and phyllosphere, suggesting that poultry manure may have a stronger impact on lettuce resistomes. The ARG profiles were significantly correlated with the bacterial community, and the enrichment of soil and plant resistomes was strongly affected by the bacterial taxa including Solibacteres, Chloroflexi, Acidobacteria, Gemm-1 and Gemmatimonadetes, as revealed by the network analyses. Moreover, the overlaps of ARGs between lettuce tissues and soil were identified, which indicated that plant and environmental resistomes are interconnected. Our findings provide insights into the transmission routes of ARGs from manured soil to vegetables, and highlight the potential risks of plant resistome migration to the human food chain.}, }
@article {pmid31218869, year = {2019}, author = {Shen, X and Yao, YF and Li, JY and Li, Y}, title = {[Human mycobiome and diseases].}, journal = {Hua xi kou qiang yi xue za zhi = Huaxi kouqiang yixue zazhi = West China journal of stomatology}, volume = {37}, number = {3}, pages = {314-319}, pmid = {31218869}, issn = {2618-0456}, mesh = {Bacteria ; *Disease ; Female ; Fungi ; Humans ; *Microbiota ; Mouth ; *Mycobiome ; }, abstract = {The proportion of mycobiome is less than 1% of human microbiome. However, fungal community plays a key role in human health and diseases. With high-throughput sequencing applications, the structure and composition of mycobiome in the mouth, lung, gut, vagina, and skin have been analyzed, and the role of microbiome in diseases has been investigated. Mycobiome also influences the composition of bacteriome and includes key species that maintain the structure and function of microbial communities. Fungi also influence host immune responses. In this review, we summarized the mycobiome com-position at various sites and different diseases and the interactions between fungi-bacteria and fungi-host.}, }
@article {pmid31202124, year = {2019}, author = {Picardo, SL and Coburn, B and Hansen, AR}, title = {The microbiome and cancer for clinicians.}, journal = {Critical reviews in oncology/hematology}, volume = {141}, number = {}, pages = {1-12}, doi = {10.1016/j.critrevonc.2019.06.004}, pmid = {31202124}, issn = {1879-0461}, mesh = {Carcinogenesis ; Female ; Gastrointestinal Microbiome/immunology/physiology ; Humans ; Immunity/physiology ; Immunologic Factors/therapeutic use ; Immunotherapy ; Male ; Microbiota/immunology/*physiology ; Neoplasms/immunology/*microbiology/*therapy ; }, abstract = {The human microbiome is an emerging target in cancer development and therapeutics. It may be directly oncogenic, through promotion of mucosal inflammation or systemic dysregulation, or may alter anti-cancer immunity/therapy. Microorganisms within, adjacent to and distant from tumors may affect cancer progression, and interactions and differences between these populations can influence the course of disease. Here we review the microbiome as it pertains to cancer for clinicians. The microbiota of cancers including colorectal, pancreas, breast and prostate are discussed. We examine "omics" technologies, microbiota associated with tumor tissue and tumor-site fluids such as feces and urine, as well as indirect effects of the gut microbiome. We describe roles of the microbiome in immunotherapy, and how it can be modulated to improve cancer therapeutics. While research is still at an early stage, there is potential to exploit the microbiome, as modulation may increase efficacy of treatments, reduce toxicities and prevent carcinogenesis.}, }
@article {pmid31201356, year = {2019}, author = {Szafrański, SP and Kilian, M and Yang, I and Bei der Wieden, G and Winkel, A and Hegermann, J and Stiesch, M}, title = {Diversity patterns of bacteriophages infecting Aggregatibacter and Haemophilus species across clades and niches.}, journal = {The ISME journal}, volume = {13}, number = {10}, pages = {2500-2522}, pmid = {31201356}, issn = {1751-7370}, mesh = {Aggregatibacter/classification/*virology ; Bacteriophages/classification/genetics/isolation &amp; purification/*physiology ; Base Composition ; Biodiversity ; Genome, Viral ; Genomics ; Haemophilus/classification/*virology ; Host Specificity ; Humans ; Lysogeny ; Metagenome ; Phylogeny ; Prophages/classification/genetics/isolation &amp; purification/physiology ; }, abstract = {Aggregatibacter and Haemophilus species are relevant human commensals and opportunistic pathogens. Consequently, their bacteriophages may have significant impact on human microbial ecology and pathologies. Our aim was to reveal the prevalence and diversity of bacteriophages infecting Aggregatibacter and Haemophilus species that colonize the human body. Genome mining with comparative genomics, screening of clinical isolates, and profiling of metagenomes allowed characterization of 346 phages grouped in 52 clusters and 18 superclusters. Less than 10% of the identified phage clusters were represented by previously characterized phages. Prophage diversity patterns varied significantly for different phage types, host clades, and environmental niches. A more diverse phage community lysogenizes Haemophilus influenzae and Haemophilus parainfluenzae strains than Aggregatibacter actinomycetemcomitans and "Haemophilus ducreyi". Co-infections occurred more often in "H. ducreyi". Phages from Aggregatibacter actinomycetemcomitans preferably lysogenized strains of specific serotype. Prophage patterns shared by subspecies clades of different bacterial species suggest similar ecoevolutionary drivers. Changes in frequencies of DNA uptake signal sequences and guanine-cytosine content reflect phage-host long-term coevolution. Aggregatibacter and Haemophilus phages were prevalent at multiple oral sites. Together, these findings should help exploring the ecoevolutionary forces shaping virus-host interactions in the human microbiome. Putative lytic phages, especially phiKZ-like, may provide new therapeutic options.}, }
@article {pmid31194675, year = {2019}, author = {Bernstein, DB and Dewhirst, FE and Segrè, D}, title = {Metabolic network percolation quantifies biosynthetic capabilities across the human oral microbiome.}, journal = {eLife}, volume = {8}, number = {}, pages = {}, pmid = {31194675}, issn = {2050-084X}, support = {T32GM008764/GM/NIGMS NIH HHS/United States ; T32 GM008764/GM/NIGMS NIH HHS/United States ; R01 DE024468/DE/NIDCR NIH HHS/United States ; R01 GM121950/GM/NIGMS NIH HHS/United States ; DE-SC0012627//Biological and Environmental Research/International ; RGP0020/2016//Human Frontier Science Program/International ; NSFOCE-BSF 1635070//National Science Foundation/International ; HR0011-15-C-0091//Defense Advanced Research Projects Agency/International ; R37DE016937/DE/NIDCR NIH HHS/United States ; R37 DE016937/DE/NIDCR NIH HHS/United States ; R01GM121950/GM/NIGMS NIH HHS/United States ; R01DE024468/DE/NIDCR NIH HHS/United States ; 1457695//National Science Foundation/International ; }, mesh = {Computational Biology ; Humans ; *Metabolic Networks and Pathways ; Metagenomics ; *Microbial Interactions ; *Microbiota ; Mouth/*microbiology ; }, abstract = {The biosynthetic capabilities of microbes underlie their growth and interactions, playing a prominent role in microbial community structure. For large, diverse microbial communities, prediction of these capabilities is limited by uncertainty about metabolic functions and environmental conditions. To address this challenge, we propose a probabilistic method, inspired by percolation theory, to computationally quantify how robustly a genome-derived metabolic network produces a given set of metabolites under an ensemble of variable environments. We used this method to compile an atlas of predicted biosynthetic capabilities for 97 metabolites across 456 human oral microbes. This atlas captures taxonomically-related trends in biomass composition, and makes it possible to estimate inter-microbial metabolic distances that correlate with microbial co-occurrences. We also found a distinct cluster of fastidious/uncultivated taxa, including several Saccharibacteria (TM7) species, characterized by their abundant metabolic deficiencies. By embracing uncertainty, our approach can be broadly applied to understanding metabolic interactions in complex microbial ecosystems.}, }
@article {pmid31188557, year = {2019}, author = {Kooter, I and Ilves, M and Gröllers-Mulderij, M and Duistermaat, E and Tromp, PC and Kuper, F and Kinaret, P and Savolainen, K and Greco, D and Karisola, P and Ndika, J and Alenius, H}, title = {Molecular Signature of Asthma-Enhanced Sensitivity to CuO Nanoparticle Aerosols from 3D Cell Model.}, journal = {ACS nano}, volume = {13}, number = {6}, pages = {6932-6946}, pmid = {31188557}, issn = {1936-086X}, mesh = {A549 Cells ; Aerosols/*chemistry ; Asthma/*metabolism ; Cells, Cultured ; Copper/chemistry/*pharmacology ; Humans ; Metal Nanoparticles/*chemistry ; Respiratory Mucosa/*drug effects/metabolism ; *Transcriptome ; }, abstract = {More than 5% of any population suffers from asthma, and there are indications that these individuals are more sensitive to nanoparticle aerosols than the healthy population. We used an air-liquid interface model of inhalation exposure to investigate global transcriptomic responses in reconstituted three-dimensional airway epithelia of healthy and asthmatic subjects exposed to pristine (nCuO) and carboxylated (nCuO[COOH]) copper oxide nanoparticle aerosols. A dose-dependent increase in cytotoxicity (highest in asthmatic donor cells) and pro-inflammatory signaling within 24 h confirmed the reliability and sensitivity of the system to detect acute inhalation toxicity. Gene expression changes between nanoparticle-exposed versus air-exposed cells were investigated. Hierarchical clustering based on the expression profiles of all differentially expressed genes (DEGs), cell-death-associated DEGs (567 genes), or a subset of 48 highly overlapping DEGs categorized all samples according to "exposure severity", wherein nanoparticle surface chemistry and asthma are incorporated into the dose-response axis. For example, asthmatics exposed to low and medium dose nCuO clustered with healthy donor cells exposed to medium and high dose nCuO, respectively. Of note, a set of genes with high relevance to mucociliary clearance were observed to distinctly differentiate asthmatic and healthy donor cells. These genes also responded differently to nCuO and nCuO[COOH] nanoparticles. Additionally, because response to transition-metal nanoparticles was a highly enriched Gene Ontology term (FDR 8 × 10[-13]) from the subset of 48 highly overlapping DEGs, these genes may represent biomarkers to a potentially large variety of metal/metal oxide nanoparticles.}, }
@article {pmid31186074, year = {2019}, author = {Nichols, RG and Peters, JM and Patterson, AD}, title = {Interplay Between the Host, the Human Microbiome, and Drug Metabolism.}, journal = {Human genomics}, volume = {13}, number = {1}, pages = {27}, pmid = {31186074}, issn = {1479-7364}, support = {R01 CA124533/CA/NCI NIH HHS/United States ; CA124533/CA/NCI NIH HHS/United States ; ES026684/ES/NIEHS NIH HHS/United States ; R01 ES028288/ES/NIEHS NIH HHS/United States ; R56 ES026684/ES/NIEHS NIH HHS/United States ; ES022186/ES/NIEHS NIH HHS/United States ; ES028288/ES/NIEHS NIH HHS/United States ; R01 ES022186/ES/NIEHS NIH HHS/United States ; }, mesh = {Dermatitis, Atopic/drug therapy/genetics ; Female ; Gingivitis/drug therapy/genetics ; Humans ; Inactivation, Metabolic/*genetics ; Irritable Bowel Syndrome/drug therapy/genetics ; Microbiota/*drug effects/genetics ; *Prebiotics ; Probiotics/*therapeutic use ; Vaginosis, Bacterial/drug therapy/genetics ; }, abstract = {The human microbiome is composed of four major areas including intestinal, skin, vaginal, and oral microbiomes, with each area containing unique species and unique functionalities. The human microbiome may be modulated with prebiotics, probiotics, and postbiotics to potentially aid in the treatment of diseases like irritable bowel syndrome, bacterial vaginosis, atopic dermatitis, gingivitis, obesity, or cancer. There is also potential for many of the inhabitants of the human microbiome to directly modulate host gene expression and modulate host detoxifying enzyme activity like cytochrome P450s (CYPs), dehydrogenases, and carboxylesterases. Therefore, the microbiome may be important to consider during drug discovery, risk assessment, and dosing regimens for various diseases given that the human microbiome has been shown to impact host detoxification processes.}, }
@article {pmid31183114, year = {2019}, author = {Zhao, L and Xu, J and Shang, X and Li, X and Li, Q and Li, S}, title = {Synaptic memory devices from CoO/Nb:SrTiO3 junction.}, journal = {Royal Society open science}, volume = {6}, number = {4}, pages = {181098}, pmid = {31183114}, issn = {2054-5703}, abstract = {Non-volatile memristors are promising for future hardware-based neurocomputation application because they are capable of emulating biological synaptic functions. Various material strategies have been studied to pursue better device performance, such as lower energy cost, better biological plausibility, etc. In this work, we show a novel design for non-volatile memristor based on CoO/Nb:SrTiO3 heterojunction. We found the memristor intrinsically exhibited resistivity switching behaviours, which can be ascribed to the migration of oxygen vacancies and charge trapping and detrapping at the heterojunction interface. The carrier trapping/detrapping level can be finely adjusted by regulating voltage amplitudes. Gradual conductance modulation can therefore be realized by using proper voltage pulse stimulations. And the spike-timing-dependent plasticity, an important Hebbian learning rule, has been implemented in the device. Our results indicate the possibility of achieving artificial synapses with CoO/Nb:SrTiO3 heterojunction. Compared with filamentary type of the synaptic device, our device has the potential to reduce energy consumption, realize large-scale neuromorphic system and work more reliably, since no structural distortion occurs.}, }
@article {pmid31180804, year = {2019}, author = {Mark Welch, JL and Dewhirst, FE and Borisy, GG}, title = {Biogeography of the Oral Microbiome: The Site-Specialist Hypothesis.}, journal = {Annual review of microbiology}, volume = {73}, number = {}, pages = {335-358}, pmid = {31180804}, issn = {1545-3251}, support = {R01 DE016937/DE/NIDCR NIH HHS/United States ; R01 DE022586/DE/NIDCR NIH HHS/United States ; R37 DE016937/DE/NIDCR NIH HHS/United States ; }, mesh = {Humans ; *Microbiota ; Mouth/*microbiology ; Spatial Analysis ; }, abstract = {Microbial communities are complex and dynamic, composed of hundreds of taxa interacting across multiple spatial scales. Advances in sequencing and imaging technology have led to great strides in understanding both the composition and the spatial organization of these complex communities. In the human mouth, sequencing results indicate that distinct sites host microbial communities that not only are distinguishable but to a meaningful degree are composed of entirely different microbes. Imaging suggests that the spatial organization of these communities is also distinct. Together, the literature supports the idea that most oral microbes are site specialists. A clear understanding of microbiota structure at different sites in the mouth enables mechanistic studies, informs the generation of hypotheses, and strengthens the position of oral microbiology as a model system for microbial ecology in general.}, }
@article {pmid31171383, year = {2019}, author = {Hitchings, R and Kelly, L}, title = {Predicting and Understanding the Human Microbiome's Impact on Pharmacology.}, journal = {Trends in pharmacological sciences}, volume = {40}, number = {7}, pages = {495-505}, pmid = {31171383}, issn = {1873-3735}, support = {TL1 TR001072/TR/NCATS NIH HHS/United States ; TL1 TR002557/TR/NCATS NIH HHS/United States ; UL1 TR002556/TR/NCATS NIH HHS/United States ; }, mesh = {Actinobacteria/metabolism ; Animals ; Bacteroides/metabolism ; Helicobacter pylori/metabolism ; Humans ; Microbiota/drug effects/*physiology ; Pharmaceutical Preparations/*metabolism ; Pharmacokinetics ; Precision Medicine/methods ; }, abstract = {Our bodies each possess a unique and dynamic collection of microbes and viruses, collectively the 'microbiome', with distinct metabolic capacities from our human cells. Unforeseen modification of drugs by the microbiome can drastically alter their clinical effectiveness, with the most dramatic cases leading to fatal drug interactions. Pharmaceuticals can be activated, deactivated, toxified, or release metabolites that alter the 'canonical' pharmacokinetics of the drug. Thus, predicting and characterizing microbe-drug interactions is necessary to develop and implement personalized drug administration protocols and, more broadly, to improve drug safety and efficacy. In this review, we focus on microbiome-driven alterations to drug pharmacokinetics and provide a research framework for pharmacologists interested in characterizing microbiome interactions with any drug of interest.}, }
@article {pmid31169619, year = {2019}, author = {Wijeyesekera, A and Wagner, J and De Goffau, M and Thurston, S and Rodrigues Sabino, A and Zaher, S and White, D and Ridout, J and Peters, MJ and Ramnarayan, P and Branco, RG and Torok, ME and Valla, F and Meyer, R and Klein, N and Frost, G and Parkhill, J and Holmes, E and Pathan, N}, title = {Multi-Compartment Profiling of Bacterial and Host Metabolites Identifies Intestinal Dysbiosis and Its Functional Consequences in the Critically Ill Child.}, journal = {Critical care medicine}, volume = {47}, number = {9}, pages = {e727-e734}, pmid = {31169619}, issn = {1530-0293}, support = {/WT_/Wellcome Trust/United Kingdom ; 082372/WT_/Wellcome Trust/United Kingdom ; MR/N029399/1/MRC_/Medical Research Council/United Kingdom ; /DH_/Department of Health/United Kingdom ; }, mesh = {Adolescent ; Child ; Child, Preschool ; Chromatography, Liquid ; Cresols/urine ; *Critical Illness ; Dysbiosis/*diagnosis ; Fatty Acids, Volatile/analysis ; Feces/chemistry/microbiology ; Female ; Formates/urine ; Gastrointestinal Microbiome/*physiology ; Hippurates/urine ; Humans ; Infant ; Intensive Care Units, Pediatric/*organization &amp; administration ; Magnetic Resonance Imaging ; Male ; Mass Spectrometry ; Metabolomics ; Prospective Studies ; RNA, Ribosomal, 16S ; Respiration, Artificial/statistics &amp; numerical data ; Severity of Illness Index ; Sulfuric Acid Esters/urine ; Time Factors ; United Kingdom ; Urine/chemistry/microbiology ; }, abstract = {OBJECTIVES: Adverse physiology and antibiotic exposure devastate the intestinal microbiome in critical illness. Time and cost implications limit the immediate clinical potential of microbial sequencing to identify or treat intestinal dysbiosis. Here, we examined whether metabolic profiling is a feasible method of monitoring intestinal dysbiosis in critically ill children.<br><br>DESIGN: Prospective multicenter cohort study.<br><br>SETTING: Three U.K.-based PICUs.<br><br>PATIENTS: Mechanically ventilated critically ill (n = 60) and age-matched healthy children (n = 55).<br><br>INTERVENTIONS: Collection of urine and fecal samples in children admitted to the PICU. A single fecal and urine sample was collected in healthy controls.<br><br>MEASUREMENTS AND MAIN RESULTS: Untargeted and targeted metabolic profiling using 1H-nuclear magnetic resonance spectroscopy and liquid chromatography-mass spectrometry or urine and fecal samples. This was integrated with analysis of fecal bacterial 16S ribosomal RNA profiles and clinical disease severity indicators. We observed separation of global urinary and fecal metabolic profiles in critically ill compared with healthy children. Urinary excretion of mammalian-microbial co-metabolites hippurate, 4-cresol sulphate, and formate were reduced in critical illness compared with healthy children. Reduced fecal excretion of short-chain fatty acids (including butyrate, propionate, and acetate) were observed in the patient cohort, demonstrating that these metabolites also distinguished between critical illness and health. Dysregulation of intestinal bile metabolism was evidenced by increased primary and reduced secondary fecal bile acid excretion. Fecal butyrate correlated with days free of intensive care at 30 days (r = 0.38; p = 0.03), while urinary formate correlated inversely with vasopressor requirement (r = -0.2; p = 0.037).<br><br>CONCLUSIONS: Disruption to the functional activity of the intestinal microbiome may result in worsening organ failure in the critically ill child. Profiling of bacterial metabolites in fecal and urine samples may support identification and treatment of intestinal dysbiosis in critical illness.}, }
@article {pmid31169073, year = {2019}, author = {Hsu, T and Gemmell, MR and Franzosa, EA and Berry, S and Mukhopadhya, I and Hansen, R and Michaud, M and Nielsen, H and Miller, WG and Nielsen, H and Bajaj-Elliott, M and Huttenhower, C and Garrett, WS and Hold, GL}, title = {Comparative genomics and genome biology of Campylobacter showae.}, journal = {Emerging microbes &amp; infections}, volume = {8}, number = {1}, pages = {827-840}, pmid = {31169073}, issn = {2222-1751}, support = {R24 DK110499/DK/NIDDK NIH HHS/United States ; }, mesh = {Bacterial Proteins/genetics ; Campylobacter/classification/*genetics/isolation &amp; purification/pathogenicity ; Campylobacter Infections/*microbiology ; Crohn Disease/microbiology ; Gastroenteritis/microbiology ; *Genome, Bacterial ; Genomics ; Humans ; Phenotype ; Phylogeny ; Virulence ; Virulence Factors/genetics ; }, abstract = {Campylobacter showae a bacterium historically linked to gingivitis and periodontitis, has recently been associated with inflammatory bowel disease and colorectal cancer. Our aim was to generate genome sequences for new clinical C. showae strains and identify functional properties explaining their pathogenic potential. Eight C. showae genomes were assessed, four strains isolated from inflamed gut tissues from paediatric Crohn's disease patients, three strains from colonic adenomas, and one from a gastroenteritis patient stool. Genome assemblies were analyzed alongside the only 3 deposited C. showae genomes. The pangenome from these 11 strains consisted of 4686 unique protein families, and the core genome size was estimated at 1050 ± 15 genes with each new genome contributing an additional 206 ± 16 genes. Functional assays indicated that colonic strains segregated into 2 groups: adherent/invasive vs. non-adherent/non-invasive strains. The former possessed Type IV secretion machinery and S-layer proteins, while the latter contained Cas genes and other CRISPR associated proteins. Comparison of gene profiles with strains in Human Microbiome Project metagenomes showed that gut-derived isolates share genes specific to tongue dorsum and supragingival plaque counterparts. Our findings indicate that C. showae strains are phenotypically and genetically diverse and suggest that secretion systems may play an important role in virulence potential.}, }
@article {pmid31168910, year = {2020}, author = {Vress, D and Lim, B}, title = {Understanding the human microbiome: new icing on an old cake.}, journal = {BJOG : an international journal of obstetrics and gynaecology}, volume = {127}, number = {2}, pages = {138}, doi = {10.1111/1471-0528.15816}, pmid = {31168910}, issn = {1471-0528}, mesh = {Bacterial Infections ; Female ; Gastrointestinal Tract/immunology/*microbiology ; Humans ; *Microbiota/physiology ; Urogenital System/immunology/*microbiology ; }, }
@article {pmid31167634, year = {2019}, author = {LaPierre, N and Mangul, S and Alser, M and Mandric, I and Wu, NC and Koslicki, D and Eskin, E}, title = {MiCoP: microbial community profiling method for detecting viral and fungal organisms in metagenomic samples.}, journal = {BMC genomics}, volume = {20}, number = {Suppl 5}, pages = {423}, pmid = {31167634}, issn = {1471-2164}, support = {R01 ES021801/ES/NIEHS NIH HHS/United States ; R01 MH101782/MH/NIMH NIH HHS/United States ; K25 HL080079/HL/NHLBI NIH HHS/United States ; P01 HL028481/HL/NHLBI NIH HHS/United States ; U01 DA024417/DA/NIDA NIH HHS/United States ; T32 EB016640/EB/NIBIB NIH HHS/United States ; R01 ES022282/ES/NIEHS NIH HHS/United States ; P01 HL030568/HL/NHLBI NIH HHS/United States ; R01 GM083198/GM/NIGMS NIH HHS/United States ; }, mesh = {Algorithms ; Computational Biology/*methods ; Fungi/classification/*genetics ; *Genetic Markers ; Genome, Fungal ; Genome, Viral ; High-Throughput Nucleotide Sequencing/methods ; Humans ; Metagenomics/*methods ; *Microbiota ; Sequence Analysis, DNA/*methods ; Viruses/classification/*genetics ; }, abstract = {BACKGROUND: High throughput sequencing has spurred the development of metagenomics, which involves the direct analysis of microbial communities in various environments such as soil, ocean water, and the human body. Many existing methods based on marker genes or k-mers have limited sensitivity or are too computationally demanding for many users. Additionally, most work in metagenomics has focused on bacteria and archaea, neglecting to study other key microbes such as viruses and eukaryotes.<br><br>RESULTS: Here we present a method, MiCoP (Microbiome Community Profiling), that uses fast-mapping of reads to build a comprehensive reference database of full genomes from viruses and eukaryotes to achieve maximum read usage and enable the analysis of the virome and eukaryome in each sample. We demonstrate that mapping of metagenomic reads is feasible for the smaller viral and eukaryotic reference databases. We show that our method is accurate on simulated and mock community data and identifies many more viral and fungal species than previously-reported results on real data from the Human Microbiome Project.<br><br>CONCLUSIONS: MiCoP is a mapping-based method that proves more effective than existing methods at abundance profiling of viruses and eukaryotes in metagenomic samples. MiCoP can be used to detect the full diversity of these communities. The code, data, and documentation are publicly available on GitHub at: https://github.com/smangul1/MiCoP .}, }
@article {pmid31164901, year = {2019}, author = {Tang, ZZ and Chen, G and Hong, Q and Huang, S and Smith, HM and Shah, RD and Scholz, M and Ferguson, JF}, title = {Multi-Omic Analysis of the Microbiome and Metabolome in Healthy Subjects Reveals Microbiome-Dependent Relationships Between Diet and Metabolites.}, journal = {Frontiers in genetics}, volume = {10}, number = {}, pages = {454}, pmid = {31164901}, issn = {1664-8021}, support = {15SDG24890015/AHA/American Heart Association-American Stroke Association/United States ; P30 DK058404/DK/NIDDK NIH HHS/United States ; U01 HL108636/HL/NHLBI NIH HHS/United States ; }, abstract = {The human microbiome has been associated with health status, and risk of disease development. While the etiology of microbiome-mediated disease remains to be fully elucidated, one mechanism may be through microbial metabolism. Metabolites produced by commensal organisms, including in response to host diet, may affect host metabolic processes, with potentially protective or pathogenic consequences. We conducted multi-omic phenotyping of healthy subjects (N = 136), in order to investigate the interaction between diet, the microbiome, and the metabolome in a cross-sectional sample. We analyzed the nutrient composition of self-reported diet (3-day food records and food frequency questionnaires). We profiled the gut and oral microbiome (16S rRNA) from stool and saliva, and applied metabolomic profiling to plasma and stool samples in a subset of individuals (N = 75). We analyzed these multi-omic data to investigate the relationship between diet, the microbiome, and the gut and circulating metabolome. On a global level, we observed significant relationships, particularly between long-term diet, the gut microbiome and the metabolome. Intake of plant-derived nutrients as well as consumption of artificial sweeteners were associated with significant differences in circulating metabolites, particularly bile acids, which were dependent on gut enterotype, indicating that microbiome composition mediates the effect of diet on host physiology. Our analysis identifies dietary compounds and phytochemicals that may modulate bacterial abundance within the gut and interact with microbiome composition to alter host metabolism.}, }
@article {pmid31164869, year = {2019}, author = {Belforte, FS and Fernandez, N and Tonín Monzón, F and Rosso, AD and Quesada, S and Cimolai, MC and Millán, A and Cerrone, GE and Frechtel, GD and Burcelin, R and Coluccio Leskow, F and Penas-Steinhardt, A}, title = {Getting to Know the Gut Microbial Diversity of Metropolitan Buenos Aires Inhabitants.}, journal = {Frontiers in microbiology}, volume = {10}, number = {}, pages = {965}, pmid = {31164869}, issn = {1664-302X}, support = {T37 MD001452/MD/NIMHD NIH HHS/United States ; }, abstract = {In recent years, the field of immunology has been revolutionized by the growing understanding of the fundamental role of microbiota in the immune system function. The immune system has evolved to maintain a symbiotic relationship with these microbes. The aim of our study was to know in depth the uncharacterized metagenome of the Buenos Aires (BA) city population and its metropolitan area, being the second most populated agglomeration in the southern hemisphere. For this purpose, we evaluated 30 individuals (age: 35.23 ± 8.26 years and BMI: 23.91 ± 3.4 kg/m[2]), from the general population of BA. The hypervariable regions V3-V4 of the bacterial 16S gene was sequenced by MiSeq-Illumina system, obtaining 47526 ± 4718 sequences/sample. The dominant phyla were Bacteroidetes, Firmicutes, Proteobacteria, Verrucomicrobia, and Actinobacteria. Additionally, we compared the microbiota of BA with other westernized populations (Santiago de Chile, Rosario-Argentina, United States-Human-microbiome-project, Bologna-Italy) and the Hadza population of hunter-gatherers. The unweighted UniFrac clustered together all westernized populations, leaving the hunter-gatherer population from Hadza out. In particular, Santiago de Chile's population turns out to be the closest to BA's, principally due to the presence of Verrucomicrobiales of the genus Akkermansia. These microorganisms have been proposed as a hallmark of a healthy gut. Finally, westernized populations showed more abundant metabolism related KEEG pathways than hunter-gatherers, including carbohydrate metabolism (amino sugar and nucleotide sugar metabolism), amino acid metabolism (alanine, aspartate and glutamate metabolism), lipid metabolism, biosynthesis of secondary metabolites, and sulfur metabolism. These findings contribute to promote research and comparison of the microbiome in different human populations, in order to develop more efficient therapeutic strategies for the restoration of a healthy dialogue between host and environment.}, }
@article {pmid31163166, year = {2019}, author = {Granato, ET and Meiller-Legrand, TA and Foster, KR}, title = {The Evolution and Ecology of Bacterial Warfare.}, journal = {Current biology : CB}, volume = {29}, number = {11}, pages = {R521-R537}, doi = {10.1016/j.cub.2019.04.024}, pmid = {31163166}, issn = {1879-0445}, support = {/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; 209397/Z/17/Z/WT_/Wellcome Trust/United Kingdom ; }, mesh = {Aggression ; *Bacterial Physiological Phenomena ; *Biological Evolution ; *Microbial Interactions ; }, abstract = {Bacteria have evolved a wide range of mechanisms to harm and kill their competitors, including chemical, mechanical and biological weapons. Here we review the incredible diversity of bacterial weapon systems, which comprise antibiotics, toxic proteins, mechanical weapons that stab and pierce, viruses, and more. The evolution of bacterial weapons is shaped by many factors, including cell density and nutrient abundance, and how strains are arranged in space. Bacteria also employ a diverse range of combat behaviours, including pre-emptive attacks, suicidal attacks, and reciprocation (tit-for-tat). However, why bacteria carry so many weapons, and why they are so often used, remains poorly understood. By comparison with animals, we argue that the way that bacteria live - often in dense and genetically diverse communities - is likely to be key to their aggression as it encourages them to dig in and fight alongside their clonemates. The intensity of bacterial aggression is such that it can strongly affect communities, via complex coevolutionary and eco-evolutionary dynamics, which influence species over space and time. Bacterial warfare is a fascinating topic for ecology and evolution, as well as one of increasing relevance. Understanding how bacteria win wars is important for the goal of manipulating the human microbiome and other important microbial systems.}, }
@article {pmid31158845, year = {2019}, author = {Zimmermann, M and Zimmermann-Kogadeeva, M and Wegmann, R and Goodman, AL}, title = {Mapping human microbiome drug metabolism by gut bacteria and their genes.}, journal = {Nature}, volume = {570}, number = {7762}, pages = {462-467}, pmid = {31158845}, issn = {1476-4687}, support = {162256/SNSF_/Swiss National Science Foundation/Switzerland ; R35 GM118159/GM/NIGMS NIH HHS/United States ; UL1 TR001863/TR/NCATS NIH HHS/United States ; R01 DK114793/DK/NIDDK NIH HHS/United States ; 178482/SNSF_/Swiss National Science Foundation/Switzerland ; DP2 GM105456/GM/NIGMS NIH HHS/United States ; U01 AI124275/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Bacteria/classification/enzymology/*genetics/*metabolism ; Bacteroides thetaiotaomicron/enzymology/genetics/metabolism ; Diltiazem/metabolism ; Female ; Gastrointestinal Microbiome/*genetics/physiology ; Genome, Bacterial/genetics ; Germ-Free Life ; Humans ; Male ; Mice ; Pharmaceutical Preparations/administration &amp; dosage/*metabolism ; Substrate Specificity ; }, abstract = {Individuals vary widely in their responses to medicinal drugs, which can be dangerous and expensive owing to treatment delays and adverse effects. Although increasing evidence implicates the gut microbiome in this variability, the molecular mechanisms involved remain largely unknown. Here we show, by measuring the ability of 76 human gut bacteria from diverse clades to metabolize 271 orally administered drugs, that many drugs are chemically modified by microorganisms. We combined high-throughput genetic analyses with mass spectrometry to systematically identify microbial gene products that metabolize drugs. These microbiome-encoded enzymes can directly and substantially affect intestinal and systemic drug metabolism in mice, and can explain the drug-metabolizing activities of human gut bacteria and communities on the basis of their genomic contents. These causal links between the gene content and metabolic activities of the microbiota connect interpersonal variability in microbiomes to interpersonal differences in drug metabolism, which has implications for medical therapy and drug development across multiple disease indications.}, }
@article {pmid31154251, year = {2019}, author = {Williams, DW and Gibson, G}, title = {Classification of individuals and the potential to detect sexual contact using the microbiome of the pubic region.}, journal = {Forensic science international. Genetics}, volume = {41}, number = {}, pages = {177-187}, doi = {10.1016/j.fsigen.2019.05.004}, pmid = {31154251}, issn = {1878-0326}, mesh = {Adult ; Aged ; Female ; *Genitalia ; Hair/*microbiology ; Humans ; Male ; *Microbiota ; Middle Aged ; Principal Component Analysis ; RNA, Ribosomal, 16S ; Sequence Analysis, RNA ; *Sexual Behavior ; Young Adult ; }, abstract = {In the absence of traditional DNA evidence, detection of sexual contact during intercourse is an important need for forensic analysis that might be addressed by studies of the pubic microbiome. Since 16S sequencing of various other body parts has shown that the microbiome may be individualizing, we reasoned that transfer of the assailant's microbiome to a victim might be detectable. Microbiome profiles were generated from pubic hairs and swabs taken from the pubic mound region of 12 couples and 19 singles, and evaluated for similarity over an average of four collection times with varying degrees of self-reported sexual activity. A model constructed using a Random Forest classifier was able to predict samples belonging to the same individual collected up to 6 months apart, demonstrating the stability of the pubic mound microbiome over this time frame. Couples were found to be significantly more similar to one another than to unrelated members of the opposite sex, in proportion to shared sexual activity. Further analyses using the Deblur method to assign operational taxonomic units (OTUs) establish that at least 10% of the victim's pubic microbiome must be derived from the attacker in order to detect transfer, but that single transfer events will not generally be discovered. Nevertheless, Bayesian SourceTracker software is shown to have potential to establish that sexual contact occurred when the assailant is known, or to exonerate suspects as contributors to a mixed microbiome. Our results establish limited potential of the pubic hair/pubic area microbiome as a tool for forensic associations.}, }
@article {pmid31142868, year = {2019}, author = {}, title = {After the Integrative Human Microbiome Project, what's next for the microbiome community?.}, journal = {Nature}, volume = {569}, number = {7758}, pages = {599}, doi = {10.1038/d41586-019-01674-w}, pmid = {31142868}, issn = {1476-4687}, mesh = {Female ; Humans ; Infant, Newborn ; *Microbiota ; Pregnancy ; *Premature Birth ; Vagina ; }, }
@article {pmid31142863, year = {2019}, author = {Proctor, L}, title = {Priorities for the next 10 years of human microbiome research.}, journal = {Nature}, volume = {569}, number = {7758}, pages = {623-625}, pmid = {31142863}, issn = {1476-4687}, mesh = {Biomedical Research/economics/*trends ; Female ; Holistic Health ; Host Microbial Interactions/immunology/*physiology ; Humans ; Infant ; Infant, Newborn ; Microbiota/*physiology ; National Institutes of Health (U.S.)/economics ; Species Specificity ; Time Factors ; Tissue Distribution ; United States ; }, }
@article {pmid31142855, year = {2019}, author = {Lloyd-Price, J and Arze, C and Ananthakrishnan, AN and Schirmer, M and Avila-Pacheco, J and Poon, TW and Andrews, E and Ajami, NJ and Bonham, KS and Brislawn, CJ and Casero, D and Courtney, H and Gonzalez, A and Graeber, TG and Hall, AB and Lake, K and Landers, CJ and Mallick, H and Plichta, DR and Prasad, M and Rahnavard, G and Sauk, J and Shungin, D and Vázquez-Baeza, Y and White, RA and ,  and Braun, J and Denson, LA and Jansson, JK and Knight, R and Kugathasan, S and McGovern, DPB and Petrosino, JF and Stappenbeck, TS and Winter, HS and Clish, CB and Franzosa, EA and Vlamakis, H and Xavier, RJ and Huttenhower, C}, title = {Multi-omics of the gut microbial ecosystem in inflammatory bowel diseases.}, journal = {Nature}, volume = {569}, number = {7758}, pages = {655-662}, pmid = {31142855}, issn = {1476-4687}, support = {U01 DK062413/DK/NIDDK NIH HHS/United States ; P30 DK043351/DK/NIDDK NIH HHS/United States ; P30 DK078392/DK/NIDDK NIH HHS/United States ; U54 DE023798/DE/NIDCR NIH HHS/United States ; R01 HG005969/HG/NHGRI NIH HHS/United States ; P01 DK046763/DK/NIDDK NIH HHS/United States ; UL1 TR001881/TR/NCATS NIH HHS/United States ; R24 DK110499/DK/NIDDK NIH HHS/United States ; U54 DK102557/DK/NIDDK NIH HHS/United States ; P30 DK040561/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Fungi/pathogenicity ; Gastrointestinal Microbiome/*genetics/immunology ; Health ; Humans ; Inflammatory Bowel Diseases/immunology/*microbiology/therapy/virology ; Phylogeny ; Species Specificity ; Transcriptome ; Viruses/pathogenicity ; }, abstract = {Inflammatory bowel diseases, which include Crohn's disease and ulcerative colitis, affect several million individuals worldwide. Crohn's disease and ulcerative colitis are complex diseases that are heterogeneous at the clinical, immunological, molecular, genetic, and microbial levels. Individual contributing factors have been the focus of extensive research. As part of the Integrative Human Microbiome Project (HMP2 or iHMP), we followed 132 subjects for one year each to generate integrated longitudinal molecular profiles of host and microbial activity during disease (up to 24 time points each; in total 2,965 stool, biopsy, and blood specimens). Here we present the results, which provide a comprehensive view of functional dysbiosis in the gut microbiome during inflammatory bowel disease activity. We demonstrate a characteristic increase in facultative anaerobes at the expense of obligate anaerobes, as well as molecular disruptions in microbial transcription (for example, among clostridia), metabolite pools (acylcarnitines, bile acids, and short-chain fatty acids), and levels of antibodies in host serum. Periods of disease activity were also marked by increases in temporal variability, with characteristic taxonomic, functional, and biochemical shifts. Finally, integrative analysis identified microbial, biochemical, and host factors central to this dysregulation. The study's infrastructure resources, results, and data, which are available through the Inflammatory Bowel Disease Multi'omics Database (http://ibdmdb.org), provide the most comprehensive description to date of host and microbial activities in inflammatory bowel diseases.}, }
@article {pmid31142853, year = {2019}, author = {, }, title = {The Integrative Human Microbiome Project.}, journal = {Nature}, volume = {569}, number = {7758}, pages = {641-648}, pmid = {31142853}, issn = {1476-4687}, support = {U54 DK102557/DK/NIDDK NIH HHS/United States ; U54 HD080784/HD/NICHD NIH HHS/United States ; U54 DK102556/DK/NIDDK NIH HHS/United States ; R01 HD092415/HD/NICHD NIH HHS/United States ; UH3 AI083263/AI/NIAID NIH HHS/United States ; U54 DE023786/DE/NIDCR NIH HHS/United States ; }, mesh = {Diet ; Female ; Gastrointestinal Microbiome/physiology ; Host Microbial Interactions/physiology ; Humans ; Infant, Newborn ; *Infant, Premature ; Infections/complications/microbiology ; Inflammatory Bowel Diseases/*microbiology ; *Microbiota/physiology ; National Institutes of Health (U.S.)/*organization &amp; administration ; Prediabetic State/complications/*microbiology ; Pregnancy ; Research/*organization &amp; administration ; Time Factors ; United States ; Vagina/microbiology ; }, abstract = {The NIH Human Microbiome Project (HMP) has been carried out over ten years and two phases to provide resources, methods, and discoveries that link interactions between humans and their microbiomes to health-related outcomes. The recently completed second phase, the Integrative Human Microbiome Project, comprised studies of dynamic changes in the microbiome and host under three conditions: pregnancy and preterm birth; inflammatory bowel diseases; and stressors that affect individuals with prediabetes. The associated research begins to elucidate mechanisms of host-microbiome interactions under these conditions, provides unique data resources (at the HMP Data Coordination Center), and represents a paradigm for future multi-omic studies of the human microbiome.}, }
@article {pmid31142849, year = {2019}, author = {Fettweis, JM and Serrano, MG and Brooks, JP and Edwards, DJ and Girerd, PH and Parikh, HI and Huang, B and Arodz, TJ and Edupuganti, L and Glascock, AL and Xu, J and Jimenez, NR and Vivadelli, SC and Fong, SS and Sheth, NU and Jean, S and Lee, V and Bokhari, YA and Lara, AM and Mistry, SD and Duckworth, RA and Bradley, SP and Koparde, VN and Orenda, XV and Milton, SH and Rozycki, SK and Matveyev, AV and Wright, ML and Huzurbazar, SV and Jackson, EM and Smirnova, E and Korlach, J and Tsai, YC and Dickinson, MR and Brooks, JL and Drake, JI and Chaffin, DO and Sexton, AL and Gravett, MG and Rubens, CE and Wijesooriya, NR and Hendricks-Muñoz, KD and Jefferson, KK and Strauss, JF and Buck, GA}, title = {The vaginal microbiome and preterm birth.}, journal = {Nature medicine}, volume = {25}, number = {6}, pages = {1012-1021}, pmid = {31142849}, issn = {1546-170X}, support = {UH2 AI083263/AI/NIAID NIH HHS/United States ; R21 HD092965/HD/NICHD NIH HHS/United States ; U54 HD080784/HD/NICHD NIH HHS/United States ; R25 GM090084/GM/NIGMS NIH HHS/United States ; R01 HD092415/HD/NICHD NIH HHS/United States ; UH3 AI083263/AI/NIAID NIH HHS/United States ; U54 DE023786/DE/NIDCR NIH HHS/United States ; }, mesh = {Adult ; Black or African American ; Biodiversity ; Cohort Studies ; Cytokines/metabolism ; Female ; Host Microbial Interactions/immunology ; Humans ; Infant, Newborn ; Inflammation Mediators/metabolism ; Longitudinal Studies ; Metagenomics ; *Microbiota/genetics/immunology ; Premature Birth/etiology/immunology/*microbiology ; Risk Factors ; United States ; Vagina/immunology/*microbiology ; Young Adult ; }, abstract = {The incidence of preterm birth exceeds 10% worldwide. There are significant disparities in the frequency of preterm birth among populations within countries, and women of African ancestry disproportionately bear the burden of risk in the United States. In the present study, we report a community resource that includes 'omics' data from approximately 12,000 samples as part of the integrative Human Microbiome Project. Longitudinal analyses of 16S ribosomal RNA, metagenomic, metatranscriptomic and cytokine profiles from 45 preterm and 90 term birth controls identified harbingers of preterm birth in this cohort of women predominantly of African ancestry. Women who delivered preterm exhibited significantly lower vaginal levels of Lactobacillus crispatus and higher levels of BVAB1, Sneathia amnii, TM7-H1, a group of Prevotella species and nine additional taxa. The first representative genomes of BVAB1 and TM7-H1 are described. Preterm-birth-associated taxa were correlated with proinflammatory cytokines in vaginal fluid. These findings highlight new opportunities for assessment of the risk of preterm birth.}, }
@article {pmid31140702, year = {2019}, author = {Varoni, EM and Bavarian, R and Robledo-Sierra, J and Porat Ben-Amy, D and Wade, WG and Paster, B and Kerr, R and Peterson, DE and Frandsen Lau, E}, title = {World Workshop on Oral Medicine VII: Targeting the microbiome for oral medicine specialists-Part 1. A methodological guide.}, journal = {Oral diseases}, volume = {25 Suppl 1}, number = {}, pages = {12-27}, doi = {10.1111/odi.13063}, pmid = {31140702}, issn = {1601-0825}, support = {Steering guidance regarding additional text for ac//World Workshop on Oral Medicine VII/ ; }, mesh = {Congresses as Topic ; High-Throughput Nucleotide Sequencing ; Humans ; *Metagenome ; *Microbiota ; *Mouth Diseases ; *Oral Medicine ; Specialization ; }, abstract = {Advances in high-throughput sequencing technologies have allowed for a rapid increase in knowledge about the human microbiome in both healthy and diseased states, which is expected to increase our understanding of multifactorial diseases. The World Workshop on Oral Medicine VII chose the microbiome as one of its topics of focus. Part 1 of this review provides updated knowledge in the field of microbiome research, describes the advantages and disadvantages of currently available sequencing technologies, and proposes a seven-step "recipe" for designing and performing studies that is supported by contemporary evidence. Part 2 of this review in a companion paper discusses the results of high-throughput sequencing studies published to date on the microbiota associated with oral mucosal diseases. The goal of this collective enterprise is to encourage more oral medicine specialists to become engaged in multidisciplinary collaborations to investigate the role of the microbiome in relation to oral diseases, which could potentially lead to enhanced diagnosis, risk assessment and treatment of these patients.}, }
@article {pmid31133693, year = {2019}, author = {Gilbert, JA and Lynch, SV}, title = {Community ecology as a framework for human microbiome research.}, journal = {Nature medicine}, volume = {25}, number = {6}, pages = {884-889}, pmid = {31133693}, issn = {1546-170X}, support = {P01 AI089473/AI/NIAID NIH HHS/United States ; R01 DA040532/DA/NIDA NIH HHS/United States ; R21 AI113916/AI/NIAID NIH HHS/United States ; R21 AI133765/AI/NIAID NIH HHS/United States ; }, mesh = {Biodiversity ; Computational Biology ; Ecosystem ; Host Microbial Interactions ; Humans ; *Microbiota ; Models, Biological ; Research ; }, abstract = {The field of human microbiome research has revealed the intimate co-association of humans with diverse communities of microbes in various habitats in the human body, and the necessity of these microbes for the maintenance of human health. Microbial heterogeneity between humans and across spatial and temporal gradients requires multidimensional datasets and a unifying set of theories and statistical tools to analyze the human microbiome and fully realize the potential of this field. Here we consider the utility of community ecology as a framework for the interrogation and interpretation of the human microbiome.}, }
@article {pmid31123962, year = {2019}, author = {Pulkkinen, E and Wicklund, A and Oduor, JMO and Skurnik, M and Kiljunen, S}, title = {Characterization of vB_ApiM_fHyAci03, a novel lytic bacteriophage that infects clinical Acinetobacter strains.}, journal = {Archives of virology}, volume = {164}, number = {8}, pages = {2197-2199}, pmid = {31123962}, issn = {1432-8798}, support = {TYH2018228//Special state subsidy for health science research/ ; TYH2015411//Special state subsidy for health science research/ ; }, mesh = {Acinetobacter/*virology ; Bacteriophages/*genetics ; DNA, Viral/genetics ; Genome, Viral/genetics ; Host Specificity/genetics ; Myoviridae/genetics ; Phylogeny ; }, abstract = {We present here the isolation and characterization of Acinetobacter pittii phage vB_ApiM_fHyAci03 (fHyAci03), which belongs to the family Myoviridae. The fHyAci03 genome was found to be 165,975 bp in length and predicted to contain 255 genes. While the whole genome was 92.4% identical to Acinetobacter baumannii phage KARL-1, phylogenetic analysis based on phage long distal tail fiber amino acid sequences assigned fHyAci03 and KARL-1 to different subclusters, reflecting their different host species. Together with phylogenetic analysis, genome comparisons indicated that fHyAci03 is a novel member of the subfamily Tevenvirinae. Host range experiments revealed that fHyAci03 could infect two clinical strains of Acinetobacter nosocomialis and six clinical strains of A. pittii. Thus, fHyAci03 is a novel lytic phage that infects clinical Acinetobacter strains and represents a potential new candidate to be used in phage therapy.}, }
@article {pmid31123296, year = {2019}, author = {Virtanen, S and Rantsi, T and Virtanen, A and Kervinen, K and Nieminen, P and Kalliala, I and Salonen, A}, title = {Vaginal Microbiota Composition Correlates Between Pap Smear Microscopy and Next Generation Sequencing and Associates to Socioeconomic Status.}, journal = {Scientific reports}, volume = {9}, number = {1}, pages = {7750}, pmid = {31123296}, issn = {2045-2322}, mesh = {Adult ; Bacteria/genetics ; Epithelial Cells/microbiology ; Female ; Finland ; Gardnerella vaginalis/genetics ; High-Throughput Nucleotide Sequencing/methods ; Humans ; Lactobacillus/genetics ; Microbiota/genetics ; Microscopy/methods ; Papanicolaou Test/methods ; RNA, Ribosomal, 16S/genetics ; Reproducibility of Results ; Social Class ; Vagina/*microbiology ; Vaginal Smears/*methods ; Vaginosis, Bacterial/diagnosis/*genetics/microbiology ; }, abstract = {Recent research on vaginal microbiota relies on high throughput sequencing while microscopic methods have a long history in clinical use. We investigated the correspondence between microscopic findings of Pap smears and the vaginal microbiota composition determined by next generation sequencing among 50 asymptomatic women. Both methods produced coherent results regarding the distinction between Lactobacillus-dominant versus mixed microbiota, reassuring gynaecologists for the use of Pap smear or wet mount microscopy for rapid evaluation of vaginal bacteria as part of diagnosis. Cytologic findings identified women with bacterial vaginosis and revealed that cytolysis of vaginal epithelial cells is associated to Lactobacillus crispatus-dominated microbiota. Education and socio-economic status were associated to the vaginal microbiota variation. Our results highlight the importance of including socio-economic status as a co-factor in future vaginal microbiota studies.}, }
@article {pmid31122279, year = {2019}, author = {Ross, AA and Rodrigues Hoffmann, A and Neufeld, JD}, title = {The skin microbiome of vertebrates.}, journal = {Microbiome}, volume = {7}, number = {1}, pages = {79}, pmid = {31122279}, issn = {2049-2618}, mesh = {Animals ; Bacteria/classification ; Biological Evolution ; High-Throughput Nucleotide Sequencing ; Humans ; *Microbiota ; Skin/*microbiology ; Vertebrates/*microbiology ; }, abstract = {The skin constitutes the primary physical barrier between vertebrates and their external environment. Characterization of skin microorganisms is essential for understanding how a host evolves in association with its microbial symbionts, modeling immune system development, diagnosing illnesses, and exploring the origins of potential zoonoses that affect humans. Although many studies have characterized the human microbiome with culture-independent techniques, far less is known about the skin microbiome of other mammals, amphibians, birds, fish, and reptiles. The aim of this review is to summarize studies that have leveraged high-throughput sequencing to better understand the skin microorganisms that associate with members of classes within the subphylum Vertebrata. Specifically, links will be explored between the skin microbiome and vertebrate characteristics, including geographic location, biological sex, animal interactions, diet, captivity, maternal transfer, and disease. Recent literature on parallel patterns between host evolutionary history and their skin microbial communities, or phylosymbiosis, will also be analyzed. These factors must be considered when designing future microbiome studies to ensure that the conclusions drawn from basic research translate into useful applications, such as probiotics and successful conservation strategies for endangered and threatened animals.}, }
@article {pmid31121812, year = {2019}, author = {Biesiekierski, JR and Jalanka, J and Staudacher, HM}, title = {Can Gut Microbiota Composition Predict Response to Dietary Treatments?.}, journal = {Nutrients}, volume = {11}, number = {5}, pages = {}, pmid = {31121812}, issn = {2072-6643}, mesh = {Animals ; Bacteria/classification/isolation &amp; purification ; Blood Glucose/analysis ; Diet ; Gastrointestinal Microbiome/*physiology ; Humans ; Irritable Bowel Syndrome/*diet therapy/*microbiology ; Mice ; Obesity/*diet therapy/*microbiology ; Treatment Outcome ; Weight Loss ; }, abstract = {Dietary intervention is a challenge in clinical practice because of inter-individual variability in clinical response. Gut microbiota is mechanistically relevant for a number of disease states and consequently has been incorporated as a key variable in personalised nutrition models within the research context. This paper aims to review the evidence related to the predictive capacity of baseline microbiota for clinical response to dietary intervention in two specific health conditions, namely, obesity and irritable bowel syndrome (IBS). Clinical trials and larger predictive modelling studies were identified and critically evaluated. The findings reveal inconsistent evidence to support baseline microbiota as an accurate predictor of weight loss or glycaemic response in obesity, or as a predictor of symptom improvement in irritable bowel syndrome, in dietary intervention trials. Despite advancement in quantification methodologies, research in this area remains challenging and larger scale studies are needed until personalised nutrition is realistically achievable and can be translated to clinical practice.}, }
@article {pmid31117024, year = {2019}, author = {Amato, KR}, title = {Missing Links: the Role of Primates in Understanding the Human Microbiome.}, journal = {mSystems}, volume = {4}, number = {3}, pages = {}, pmid = {31117024}, issn = {2379-5077}, abstract = {The gut microbiome can influence host energy balances and metabolic programming. While this information is valuable in a disease context, it also has important implications for understanding host energetics from an ecological and evolutionary perspective. Here I argue that gut microbial influences on host life history-the timing of events that make up an organism's life-are an overlooked but robust area of study given that variation in life history is linked directly to host energetic budgets and allocation patterns. Additionally, while cultural influences on life history complicate the exploration of these links in humans, nonhuman primates represent an alternative system in which more robust associations can be made. By integrating human and nonhuman primate microbiome research within the context of life history theory, we will be able to more effectively pinpoint microbial contributions to host phenotypes. This information will improve our understanding of host-microbe interactions in health and disease and will transform the fields of ecology and evolution more generally.}, }
@article {pmid31113222, year = {2019}, author = {Lew, KN and Starkweather, A and Cong, X and Judge, M}, title = {A Mechanistic Model of Gut-Brain Axis Perturbation and High-Fat Diet Pathways to Gut Microbiome Homeostatic Disruption, Systemic Inflammation, and Type 2 Diabetes.}, journal = {Biological research for nursing}, volume = {21}, number = {4}, pages = {384-399}, doi = {10.1177/1099800419849109}, pmid = {31113222}, issn = {1552-4175}, mesh = {Animals ; Diabetes Mellitus, Type 2/*metabolism ; Diet, High-Fat ; Dietary Fats/*metabolism ; *Gastrointestinal Microbiome ; Humans ; Inflammation/*metabolism ; Insulin Resistance ; Lipopolysaccharides/metabolism ; Obesity/*metabolism ; }, abstract = {Type 2 diabetes (T2D) is a highly prevalent metabolic disease, affecting nearly 10% of the American population. Although the etiopathogenesis of T2D remains poorly understood, advances in DNA sequencing technologies have allowed for sophisticated interrogation of the human microbiome, providing insight into the role of the gut microbiome in the development and progression of T2D. An emerging body of research reveals that gut-brain axis (GBA) perturbations and a high-fat diet (HFD), along with other modifiable and nonmodifiable risk factors, contribute to gut microbiome homeostatic imbalance. Homeostatic imbalance or disruption increases gut wall permeability and facilitates translocation of endotoxins (lipopolysaccharides) into the circulation with resultant systemic inflammation. Chronic, low-grade systemic inflammation ensues with pro-inflammatory pathways activated, contributing to obesity, insulin resistance (IR), pancreatic β-cell decline, and, thereby, T2D. While GBA perturbations and HFD are implicated in provoking these conditions, prior mechanistic models have tended to examine HFD and GBA pathways exclusively without considering their shared pathways to T2D. Addressing this gap, this article proposes a mechanistic model informed by animal and human studies to advance scientific understanding of (1) modifiable and nonmodifiable risk factors for gut microbiome homeostatic disruption, (2) HFD and GBA pathways contributing to homeostatic disruption, and (3) shared GBA and HFD pro-inflammatory pathways to obesity, IR, β-cell decline, and T2D. The proposed mechanistic model, based on the extant literature, proposes a framework for studying the complex relationships of the gut microbiome to T2D to advance study in this promising area of research.}, }
@article {pmid31107866, year = {2019}, author = {Mainali, K and Bewick, S and Vecchio-Pagan, B and Karig, D and Fagan, WF}, title = {Detecting interaction networks in the human microbiome with conditional Granger causality.}, journal = {PLoS computational biology}, volume = {15}, number = {5}, pages = {e1007037}, pmid = {31107866}, issn = {1553-7358}, mesh = {Causality ; Computational Biology ; Gastrointestinal Microbiome ; Hand/microbiology ; Humans ; *Microbial Interactions ; *Microbiota ; *Models, Biological ; Species Specificity ; Tongue/microbiology ; }, abstract = {Human microbiome research is rife with studies attempting to deduce microbial correlation networks from sequencing data. Standard correlation and/or network analyses may be misleading when taken as an indication of taxon interactions because "correlation is neither necessary nor sufficient to establish causation"; environmental filtering can lead to correlation between non-interacting taxa. Unfortunately, microbial ecologists have generally used correlation as a proxy for causality although there is a general consensus about what constitutes a causal relationship: causes both precede and predict effects. We apply one of the first causal models for detecting interactions in human microbiome samples. Specifically, we analyze a long duration, high resolution time series of the human microbiome to decipher the networks of correlation and causation of human-associated microbial genera. We show that correlation is not a good proxy for biological interaction; we observed a weak negative relationship between correlation and causality. Strong interspecific interactions are disproportionately positive, whereas almost all strong intraspecific interactions are negative. Interestingly, intraspecific interactions also appear to act at a short timescale causing vast majority of the effects within 1-3 days. We report how different taxa are involved in causal relationships with others, and show that strong interspecific interactions are rarely conserved across two body sites whereas strong intraspecific interactions are much more conserved, ranging from 33% between the gut and right-hand to 70% between the two hands. Therefore, in the absence of guiding assumptions about ecological interactions, Granger causality and related techniques may be particularly helpful for understanding the driving factors governing microbiome composition and structure.}, }
@article {pmid31102759, year = {2019}, author = {Levi Mortera, S and Soggiu, A and Vernocchi, P and Del Chierico, F and Piras, C and Carsetti, R and Marzano, V and Britti, D and Urbani, A and Roncada, P and Putignani, L}, title = {Metaproteomic investigation to assess gut microbiota shaping in newborn mice: A combined taxonomic, functional and quantitative approach.}, journal = {Journal of proteomics}, volume = {203}, number = {}, pages = {103378}, doi = {10.1016/j.jprot.2019.103378}, pmid = {31102759}, issn = {1876-7737}, mesh = {Animals ; Animals, Newborn/*microbiology ; Bacterial Proteins/analysis ; Chromatography, Liquid ; Classification ; *Gastrointestinal Microbiome ; Mice ; Mucous Membrane/chemistry ; Proteins/analysis ; Proteomics/*methods ; Tandem Mass Spectrometry ; }, abstract = {Breastfeeding is nowadays known to be one of the most critical factors contributing to the development of an efficient immune system. In the last decade, a consistent number of pieces of evidence demonstrated the relationship between a healthy organism and its gut microbiota. However, this link is still not fully understood and requires further investigation. We recently adopted a murine model to describe the impact of either maternal milk or parental genetic background, on the composition of the gut microbial population in the first weeks of life. A metaproteomic approach to such complex environments is a big challenge that requires a strong effort in both data production and analysis, including the set-up of dedicated multitasking bioinformatics pipelines. Herein we present an LC-MS/MS based investigation to monitor mouse gut microbiota in the early life, aiming at characterizing its functions and metabolic activities together with a taxonomic description in terms of operational taxonomic units. We provided a quantitative evaluation of bacterial metaproteins, taking into account differential expression results in relation to the functional and taxonomic classification, particularly with proteins from orthologues groups. This allowed the reduction of the bias arising from the presence of a high number of shared peptides, and proteins, among different bacterial species. We also focused on host mucosal proteome and its modulation, according to different microbiota composition. SIGNIFICANCE: This paper would represent a reference work for investigations on gut microbiota in early life, from both a microbiological and a functional proteomic point of view. We focused on the shaping of the mouse gut microbiota in dependence on the feeding modality, defining a reliable taxonomic description, highlighting some functional characteristics of the microbial community, and performing a first quantitative evaluation by data independent analysis in metaproteomics.}, }
@article {pmid31102465, year = {2019}, author = {Birer, C and Wright, ES}, title = {Capturing the Complex Interplay Between Drugs and the Intestinal Microbiome.}, journal = {Clinical pharmacology and therapeutics}, volume = {106}, number = {3}, pages = {501-504}, pmid = {31102465}, issn = {1532-6535}, support = {U54 AT008909/AT/NCCIH NIH HHS/United States ; }, mesh = {Dose-Response Relationship, Drug ; Drug Evaluation, Preclinical/methods ; Feces/microbiology ; Gastrointestinal Microbiome/*drug effects/*physiology ; Genes, rRNA/genetics ; Humans ; Metabolomics/methods ; Pharmacokinetics ; *Pharmacology ; }, abstract = {Predicting drug interactions, disposition, and side effects is central to the practice of clinical pharmacology. Until recently, the human microbiome has been an under-appreciated player in the dynamics of drug metabolism. It is now clear that humans are “superorganisms” with about 10-fold more microbial cells than human cells and harboring an immense diversity of microbial enzymes. Owing to the advent of new technologies, we are beginning to understand the human microbiome’s impact on clinical pharmacology.}, }
@article {pmid33267220, year = {2019}, author = {Li, J and Convertino, M}, title = {Optimal Microbiome Networks: Macroecology and Criticality.}, journal = {Entropy (Basel, Switzerland)}, volume = {21}, number = {5}, pages = {}, pmid = {33267220}, issn = {1099-4300}, abstract = {The human microbiome is an extremely complex ecosystem considering the number of bacterial species, their interactions, and its variability over space and time. Here, we untangle the complexity of the human microbiome for the Irritable Bowel Syndrome (IBS) that is the most prevalent functional gastrointestinal disorder in human populations. Based on a novel information theoretic network inference model, we detected potential species interaction networks that are functionally and structurally different for healthy and unhealthy individuals. Healthy networks are characterized by a neutral symmetrical pattern of species interactions and scale-free topology versus random unhealthy networks. We detected an inverse scaling relationship between species total outgoing information flow, meaningful of node interactivity, and relative species abundance (RSA). The top ten interacting species are also the least relatively abundant for the healthy microbiome and the most detrimental. These findings support the idea about the diminishing role of network hubs and how these should be defined considering the total outgoing information flow rather than the node degree. Macroecologically, the healthy microbiome is characterized by the highest Pareto total species diversity growth rate, the lowest species turnover, and the smallest variability of RSA for all species. This result challenges current views that posit a universal association between healthy states and the highest absolute species diversity in ecosystems. Additionally, we show how the transitory microbiome is unstable and microbiome criticality is not necessarily at the phase transition between healthy and unhealthy states. We stress the importance of considering portfolios of interacting pairs versus single node dynamics when characterizing the microbiome and of ranking these pairs in terms of their interactions (i.e., species collective behavior) that shape transition from healthy to unhealthy states. The macroecological characterization of the microbiome is useful for public health and disease diagnosis and etiognosis, while species-specific analyses can detect beneficial species leading to personalized design of pre- and probiotic treatments and microbiome engineering.}, }
@article {pmid31093759, year = {2019}, author = {Oduor, JMO and Kiljunen, S and Kadija, E and Mureithi, MW and Nyachieo, A and Skurnik, M}, title = {Genomic characterization of four novel Staphylococcus myoviruses.}, journal = {Archives of virology}, volume = {164}, number = {8}, pages = {2171-2173}, doi = {10.1007/s00705-019-04267-0}, pmid = {31093759}, issn = {1432-8798}, support = {28.06.2017 (Decision letter date)//International Society for Infectious Diseases/European Society of Clinical Microbiology and Infectious Diseases (ISID/ESCMID) Fellowships/ ; TM-17- 10301//EDUFI FELLOWSHIP (Finland)/ ; TM-18- 10752//EDUFI FELLOWSHIP (Finland)/ ; 14.10.2016 (Decision letter date)//Jane ja Aatos Erkon S&#xe4;&#xe4;ti&#xf6; (FI)/ ; }, mesh = {DNA, Viral/genetics ; Genome, Viral/genetics ; Genomics/methods ; Myoviridae/*genetics ; Phylogeny ; Sequence Analysis, DNA/methods ; Staphylococcus/*genetics ; Staphylococcus Phages/genetics ; }, abstract = {We report here the annotation of the complete genomes of four novel lytic Staphylococcus phages; Stab20, Stab21, Stab22 and Stab23. These phages have double-stranded DNA genomes ranging between 153,338 and 155,962 bp in size with terminal repeats of 10,814-12,304 bp. The genome analysis suggests that they represent new phage species within the genus Kayvirus in the subfamily Twortvirinae of the family Herelleviridae.}, }
@article {pmid31092590, year = {2019}, author = {Scott, AJ and Alexander, JL and Merrifield, CA and Cunningham, D and Jobin, C and Brown, R and Alverdy, J and O'Keefe, SJ and Gaskins, HR and Teare, J and Yu, J and Hughes, DJ and Verstraelen, H and Burton, J and O'Toole, PW and Rosenberg, DW and Marchesi, JR and Kinross, JM}, title = {International Cancer Microbiome Consortium consensus statement on the role of the human microbiome in carcinogenesis.}, journal = {Gut}, volume = {68}, number = {9}, pages = {1624-1632}, pmid = {31092590}, issn = {1468-3288}, support = {R01 CA135379/CA/NCI NIH HHS/United States ; R01 CA204403/CA/NCI NIH HHS/United States ; C42378/A25637/CRUK_/Cancer Research UK/United Kingdom ; /DH_/Department of Health/United Kingdom ; }, mesh = {Animals ; Biomedical Research/methods/trends ; *Carcinogenesis/genetics/immunology ; Colorectal Neoplasms/genetics/immunology/microbiology ; DNA Damage ; Dysbiosis/complications/immunology/microbiology ; Gastrointestinal Microbiome ; Humans ; Inflammation/microbiology ; *Microbiota ; Neoplasms/genetics/immunology/*microbiology ; }, abstract = {OBJECTIVE: In this consensus statement, an international panel of experts deliver their opinions on key questions regarding the contribution of the human microbiome to carcinogenesis.<br><br>DESIGN: International experts in oncology and/or microbiome research were approached by personal communication to form a panel. A structured, iterative, methodology based around a 1-day roundtable discussion was employed to derive expert consensus on key questions in microbiome-oncology research.<br><br>RESULTS: Some 18 experts convened for the roundtable discussion and five key questions were identified regarding: (1) the relevance of dysbiosis/an&#x2009;altered gut microbiome to carcinogenesis; (2) potential mechanisms of microbiota-induced carcinogenesis; (3) conceptual frameworks describing how the human microbiome may drive carcinogenesis; (4) causation versus association; and (5) future directions for research in the field.The panel considered that, despite mechanistic and supporting evidence from animal and human studies, there is currently no direct evidence that the human commensal microbiome is a key determinant in the aetiopathogenesis of cancer. The panel cited the lack of large longitudinal, cohort studies as a principal deciding factor and agreed that this should be a future research priority. However, while acknowledging gaps in the evidence, expert opinion was that the microbiome, alongside environmental factors and an epigenetically/genetically vulnerable host, represents one apex of a tripartite, multidirectional interactome that drives carcinogenesis.<br><br>CONCLUSION: Data from longitudinal cohort studies are needed to confirm the role of the human microbiome as a key driver in the aetiopathogenesis of cancer.}, }
@article {pmid31091091, year = {2019}, author = {Bui, TPN and Troise, AD and Fogliano, V and de Vos, WM}, title = {Anaerobic Degradation of N-ε-Carboxymethyllysine, a Major Glycation End-Product, by Human Intestinal Bacteria.}, journal = {Journal of agricultural and food chemistry}, volume = {67}, number = {23}, pages = {6594-6602}, pmid = {31091091}, issn = {1520-5118}, mesh = {Adult ; Anaerobiosis ; Bacteria/classification/genetics/isolation &amp; purification/*metabolism ; Colon/*microbiology ; Feces/microbiology ; *Gastrointestinal Microbiome ; Glycation End Products, Advanced/chemistry/*metabolism ; Glycosylation ; Humans ; Infant ; Lysine/*analogs &amp; derivatives/chemistry/metabolism ; }, abstract = {Modifications of lysine contribute to the amount of dietary advanced glycation end-products reaching the colon. However, little is known about the ability of intestinal bacteria to metabolize dietary N-ε-carboxymethyllysine (CML). Successive transfers of fecal microbiota in growth media containing CML were used to identify and isolate species able to metabolize CML under anaerobic conditions. From our study, only donors exposed to processed foods degraded CML, and anaerobic bacteria enrichments from two of them used 77 and 100% of CML. Oscillibacter and Cloacibacillus evryensis increased in the two donors after the second transfer, highlighting that the bacteria from these taxa could be candidates for anaerobic CML degradation. A tentative identification of CML metabolites produced by a pure culture of Cloacibacillus evryensis was performed by mass spectrometry: carboxymethylated biogenic amines and carboxylic acids were identified as CML degradation products. The study confirmed the ability of intestinal bacteria to metabolize CML under anoxic conditions.}, }
@article {pmid31090586, year = {2019}, author = {Chernikova, D and Yuan, I and Shaker, M}, title = {Prevention of allergy with diverse and healthy microbiota: an update.}, journal = {Current opinion in pediatrics}, volume = {31}, number = {3}, pages = {418-425}, doi = {10.1097/MOP.0000000000000766}, pmid = {31090586}, issn = {1531-698X}, mesh = {*Asthma/microbiology ; Cesarean Section ; Child ; *Dermatitis, Atopic/microbiology ; Female ; *Food Hypersensitivity/microbiology ; Humans ; Infant ; *Microbiota ; Pregnancy ; }, abstract = {PURPOSE OF REVIEW: Microbiota consist of symbiotic microscopic neighbors that interact on and within our bodies in diverse and incompletely understood ways throughout our lifetime. Though various associations with allergic disease have been described, clear effective therapeutic interventions to prevent allergy have been elusive.<br><br>RECENT FINDINGS: The human microbiome is influenced by multiple factors, including: mode of infant delivery (vaginal vs. cesarean section), breastfeeding, diet, presence of siblings and pets, exposure to antibiotics and other medications (particularly antacids), lifestyle, and developmental context. Microbial species promoting atopic responses and tolerance have been described. Specific microbiota likely act through distinct metabolic pathways to promote the health of their human hosts, optimally directing the developing immune system away from pro-allergic, Th2-dominated responses to more T-regulatory-influenced behaviors.<br><br>SUMMARY: Evidence suggests that specific healthy infant microbiome signatures may influence development of some components of the allergic march of childhood by decreasing atopic dermatitis, asthma, and food allergy. Further understanding of factors that influence healthy microbiota may lead to specific strategies tailored for early intervention and disease prevention.}, }
@article {pmid31076500, year = {2019}, author = {Ahmed, B and Cox, MJ and Cuthbertson, L}, title = {Growing up with your airway microbiota: a risky business.}, journal = {Thorax}, volume = {74}, number = {6}, pages = {525-526}, doi = {10.1136/thoraxjnl-2019-213162}, pmid = {31076500}, issn = {1468-3296}, mesh = {Humans ; *Microbiota ; Respiratory System ; *Respiratory Tract Infections ; }, }
@article {pmid31076212, year = {2019}, author = {Beghini, F and Renson, A and Zolnik, CP and Geistlinger, L and Usyk, M and Moody, TU and Thorpe, L and Dowd, JB and Burk, R and Segata, N and Jones, HE and Waldron, L}, title = {Tobacco exposure associated with oral microbiota oxygen utilization in the New York City Health and Nutrition Examination Study.}, journal = {Annals of epidemiology}, volume = {34}, number = {}, pages = {18-25.e3}, pmid = {31076212}, issn = {1873-2585}, support = {R21 AI121784/AI/NIAID NIH HHS/United States ; U24 CA180996/CA/NCI NIH HHS/United States ; }, mesh = {Adult ; Biomarkers/blood ; Cotinine/*blood ; Female ; Humans ; Male ; *Microbiota ; Mouth/*microbiology ; New York City/epidemiology ; RNA, Ribosomal, 16S/genetics ; Saliva/*chemistry ; Tobacco Smoke Pollution/*analysis ; Tobacco Smoking/*blood ; }, abstract = {PURPOSE: The effect of tobacco exposure on the oral microbiome has not been established.<br><br>METHODS: We performed amplicon sequencing of the 16S ribosomal RNA gene V4 variable region to estimate bacterial community characteristics in 259 oral rinse samples, selected based on self-reported smoking and serum cotinine levels, from the 2013-2014 New York City Health and Nutrition Examination Study. We identified differentially abundant operational taxonomic units (OTUs) by primary and secondhand tobacco exposure, and used "microbe set enrichment analysis" to assess shifts in microbial oxygen utilization.<br><br>RESULTS: Cigarette smoking was associated with depletion of aerobic OTUs (Enrichment Score test statistic ES&#xa0;=&#xa0;-0.75, P&#xa0;=&#xa0;.002) with a minority (29%) of aerobic OTUs enriched in current smokers compared with never smokers. Consistent shifts in the microbiota were observed for current cigarette smokers as for nonsmokers with secondhand exposure as measured by serum cotinine levels. Differential abundance findings were similar in crude and adjusted analyses.<br><br>CONCLUSIONS: Results support a plausible link between tobacco exposure and shifts in the oral microbiome at the population level through three lines of evidence: (1) a shift in microbiota oxygen utilization associated with primary tobacco smoke exposure; (2) consistency of abundance fold changes associated with current smoking and shifts along the gradient of secondhand smoke exposure among nonsmokers; and (3) consistency after adjusting for a priori hypothesized confounders.}, }
@article {pmid31070803, year = {2019}, author = {Rodricks, J and Huang, Y and Mantus, E and Shubat, P}, title = {Do Interactions Between Environmental Chemicals and the Human Microbiome Need to Be Considered in Risk Assessments?.}, journal = {Risk analysis : an official publication of the Society for Risk Analysis}, volume = {39}, number = {11}, pages = {2353-2358}, pmid = {31070803}, issn = {1539-6924}, support = {R01 AI129958/AI/NIAID NIH HHS/United States ; R03 HL138310/HL/NHLBI NIH HHS/United States ; }, mesh = {*Environmental Exposure ; Environmental Pollutants/*toxicity ; Humans ; *Microbiota ; Models, Animal ; *Risk Assessment ; Uncertainty ; }, abstract = {One of the most dynamic and fruitful areas of current health-related research concerns the various roles of the human microbiome in disease. Evidence is accumulating that interactions between substances in the environment and the microbiome can affect risks of disease, in both beneficial and adverse ways. Although most of the research has concerned the roles of diet and certain pharmaceutical agents, there is increasing interest in the possible roles of environmental chemicals. Chemical risk assessment has, to date, not included consideration of the influence of the microbiome. We suggest that failure to consider the possible roles of the microbiome could lead to significant error in risk assessment results. Our purpose in this commentary is to summarize some of the evidence supporting our hypothesis and to urge the risk assessment community to begin considering and influencing how results from microbiome-related research could be incorporated into chemical risk assessments. An additional emphasis in our commentary concerns the distinct possibility that research on chemical-microbiome interactions will also reduce some of the significant uncertainties that accompany current risk assessments. Of particular interest is evidence suggesting that the microbiome has an influence on variability in disease risk across populations and (of particular interest to chemical risk) in animal and human responses to chemical exposure. The possible explanatory power of the microbiome regarding sources of variability could reduce what might be the most significant source of uncertainty in chemical risk assessment.}, }
@article {pmid31064829, year = {2019}, author = {Zhu, L and Zou, Q and Cao, X and Cronan, JE}, title = {Enterococcus faecalis Encodes an Atypical Auxiliary Acyl Carrier Protein Required for Efficient Regulation of Fatty Acid Synthesis by Exogenous Fatty Acids.}, journal = {mBio}, volume = {10}, number = {3}, pages = {}, pmid = {31064829}, issn = {2150-7511}, support = {R01 AI015650/AI/NIAID NIH HHS/United States ; R37 AI015650/AI/NIAID NIH HHS/United States ; }, mesh = {Acyl Carrier Protein/genetics/*metabolism ; Bacterial Proteins/genetics/*metabolism ; Biosynthetic Pathways ; Enterococcus faecalis/genetics/*metabolism ; Fatty Acids/*metabolism ; *Gene Expression Regulation, Bacterial ; Lipid Metabolism ; Operon ; }, abstract = {Acyl carrier proteins (ACPs) play essential roles in the synthesis of fatty acids and transfer of long fatty acyl chains into complex lipids. The Enterococcus faecalis genome contains two annotated acp genes, called acpA and acpB AcpA is encoded within the fatty acid synthesis (fab) operon and appears essential. In contrast, AcpB is an atypical ACP, having only 30% residue identity with AcpA, and is not essential. Deletion of acpB has no effect on E. faecalis growth or de novo fatty acid synthesis in media lacking fatty acids. However, unlike the wild-type strain, where growth with oleic acid resulted in almost complete blockage of de novo fatty acid synthesis, the ΔacpB strain largely continued de novo fatty acid synthesis under these conditions. Blockage in the wild-type strain is due to repression of fab operon transcription, leading to levels of fatty acid synthetic proteins (including AcpA) that are insufficient to support de novo synthesis. Transcription of the fab operon is regulated by FabT, a repressor protein that binds DNA only when it is bound to an acyl-ACP ligand. Since AcpA is encoded in the fab operon, its synthesis is blocked when the operon is repressed and acpA thus cannot provide a stable supply of ACP for synthesis of the acyl-ACP ligand required for DNA binding by FabT. In contrast to AcpA, acpB transcription is unaffected by growth with exogenous fatty acids and thus provides a stable supply of ACP for conversion to the acyl-ACP ligand required for repression by FabT. Indeed, ΔacpB and ΔfabT strains have essentially the same de novo fatty acid synthesis phenotype in oleic acid-grown cultures, which argues that neither strain can form the FabT-acyl-ACP repression complex. Finally, acylated derivatives of both AcpB and AcpA were substrates for the E. faecalis enoyl-ACP reductases and for E. faecalis PlsX (acyl-ACP; phosphate acyltransferase).IMPORTANCE AcpB homologs are encoded by many, but not all, lactic acid bacteria (Lactobacillales), including many members of the human microbiome. The mechanisms regulating fatty acid synthesis by exogenous fatty acids play a key role in resistance of these bacteria to those antimicrobials targeted at fatty acid synthesis enzymes. Defective regulation can increase resistance to such inhibitors and also reduce pathogenesis.}, }
@article {pmid31059117, year = {2019}, author = {Jagodzinski, A and Zielinska, E and Laczmanski, L and Hirnle, L}, title = {The early years of life. Are they influenced by our microbiome?.}, journal = {Ginekologia polska}, volume = {90}, number = {4}, pages = {228-232}, doi = {10.5603/GP.2019.0041}, pmid = {31059117}, issn = {2543-6767}, mesh = {Child ; *Child Development ; Child, Preschool ; Gastrointestinal Microbiome ; Humans ; Hypersensitivity ; Infant ; Infant, Newborn ; *Microbiota ; Milk, Human ; Parturition ; }, abstract = {Human microbiome contains the genetic pool of bacteria and other microbes such as Achaea, fungi and viruses inhabiting the human body. It holds an immense potential to affect both physiological and pathological processes. The microbiome's composition can be defined in detail by analyzing ribosomal 16S rRNA and metagenomic tests. Recent increases in cesar- ean sections, the use of antibiotics during pregnancy, the increasing amount of prematurely born children and changes in infant nutrition have an impact on the microbiome forming process. A correlation between the bowel microbiome's com- position and the occurrence of certain diseases, especially inflammatory bowel diseases (IBD), asthma and type 1 diabetes has been demonstrated. The influence on the development of cognitive functions and behaviour has also been displayed. This correlation justifies attempts to restore the beneficial the composition of the microbiome through the use of probiotics, vaginal microflora transfer in case of cesarean section and encouraging breastfeeding. Development of multiple studies on the topic of the human microbiome and its impact on the human body is necessary in order to reach final conclusions. The aim of this article is to summarize recent findings regarding the development of the human microbiome from the first days of life and the influence of changes in its composition on human health.}, }
@article {pmid31057522, year = {2019}, author = {Fiedorová, K and Radvanský, M and Němcová, E and Grombiříková, H and Bosák, J and Černochová, M and Lexa, M and Šmajs, D and Freiberger, T}, title = {The Impact of DNA Extraction Methods on Stool Bacterial and Fungal Microbiota Community Recovery.}, journal = {Frontiers in microbiology}, volume = {10}, number = {}, pages = {821}, pmid = {31057522}, issn = {1664-302X}, abstract = {Our understanding of human gut microbiota in health and disease depends on accurate and reproducible microbial data acquisition. The critical step in this process is to apply an appropriate methodology to extract microbial DNA, since biases introduced during the DNA extraction process may result in inaccurate microbial representation. In this study, we attempted to find a DNA extraction protocol which could be effectively used to analyze both the bacterial and fungal community. We evaluated the effect of five DNA extraction methods (QIAamp DNA Stool Mini Kit, PureLink[TM] Microbiome DNA Purification Kit, ZR Fecal DNA MiniPrep[TM] Kit, NucleoSpin[®] DNA Stool Kit, and IHMS protocol Q) on bacterial and fungal gut microbiome recovery using (i) a defined system of germ-free mice feces spiked with bacterial or fungal strains, and (ii) non-spiked human feces. In our experimental setup, we confirmed that the examined methods significantly differed in efficiency and quality, which affected the identified stool microbiome composition. In addition, our results indicated that fungal DNA extraction might be prone to be affected by reagent/kit contamination, and thus an appropriate blank control should be included in mycobiome research. Overall, standardized IHMS protocol Q, recommended by the International Human Microbiome Consortium, performed the best when considering all the parameters analyzed, and thus could be applied not only in bacterial, but also in fungal microbiome research.}, }
@article {pmid31055031, year = {2019}, author = {Seferovic, MD and Pace, RM and Carroll, M and Belfort, B and Major, AM and Chu, DM and Racusin, DA and Castro, ECC and Muldrew, KL and Versalovic, J and Aagaard, KM}, title = {Visualization of microbes by 16S in situ hybridization in term and preterm placentas without intraamniotic infection.}, journal = {American journal of obstetrics and gynecology}, volume = {221}, number = {2}, pages = {146.e1-146.e23}, pmid = {31055031}, issn = {1097-6868}, support = {R01 DK089201/DK/NIDDK NIH HHS/United States ; R01 HD091731/HD/NICHD NIH HHS/United States ; R01 NR014792/NR/NINR NIH HHS/United States ; }, mesh = {Adult ; DNA Barcoding, Taxonomic ; Female ; Humans ; In Situ Hybridization ; Metagenomics ; Microbiota ; Placenta/*microbiology ; Pregnancy ; Premature Birth ; RNA, Bacterial/analysis ; *RNA, Ribosomal, 16S ; Sequence Analysis, RNA ; Term Birth ; }, abstract = {BACKGROUND: Numerous reports have documented bacteria in the placental membranes and basal plate decidua in the absence of immunopathology using histologic techniques. Similarly, independent metagenomic characterizations have identified an altered taxonomic makeup in association with spontaneous preterm birth. Here we sought to corroborate these findings by localizing presumptive intact bacteria using molecular histology within the placental microanatomy.<br><br>OBJECTIVE: Here we examined for microbes in term and preterm gestations using a signal-amplified 16S universal in situ hybridization probe set for bacterial rRNA, alongside traditional histologic methods of Warthin-Starry and Gram stains, as well as clinical culture methodologies. We further sought to differentiate accompanying 16S gene sequencing taxonomic profiles from germ-free (gnotobiotic) mouse and extraction and amplicon contamination controls.<br><br>STUDY DESIGN: Placentas were collected from a total of 53 subjects, composed of term labored (n&#xa0;= 4) and unlabored cesarean deliveries (n&#xa0;= 22) and preterm vaginal (n&#xa0;= 18) and cesarean deliveries (n&#xa0;= 8); a placenta from a single subject with clinical and histologic evident choriomanionitis was employed as a positive control (n&#xa0;= 1). The preterm cohort included spontaneous preterm birth with (n&#xa0;= 6) and without (n&#xa0;= 10) preterm premature rupture of membranes, as well as medically indicated preterm births (n&#xa0;= 10). Placental microbes were visualized using an in situ hybridization probe set designed against highly conserved regions of the bacterial 16S ribosome, which produces an amplified stable signal using branched DNA probes. Extracted bacterial nucleic acids from these same samples were subjected to 16S rRNA metagenomic sequencing (Illumina, V4) for course taxonomic analysis, alongside environmental and kit contaminant controls. A subset of unlabored, cesarean-delivered term pregnancies were also assessed with clinical culture for readily cultivatable pathogenic microbes.<br><br>RESULTS: Molecular in situ hybridization of bacterial rRNA enabled visualization and localization of low-abundance microbes after systematic high-power scanning. Despite the absence of clinical or histologic chorioamnionitis in 52 of 53 subjects, instances of 16S rRNA signal were confidently observed in 13 of 16 spontaneous preterm birth placentas, which was not significantly different from term unlabored cesarean specimens (18 of 22; P > .05). 16S rRNA signal was largely localized to the villous parenchyma and/or syncytiotrophoblast, and less commonly the chorion and the maternal intervillous space. In all term and unlabored cesarean deliveries, visualization of evident placental microbes by in situ hybridization occurred in the absence of clinical or histologic detection using conventional clinical cultivation, hematoxylin-eosin, and Gram staining. In 1 subject, appreciable villous bacteria localized to an infarction, where 16S microbial detection was confirmed by Warthin-Starry stain. In all instances, parallel sample principle coordinate analysis using Bray-Cutis distances of 16S rRNA gene sequencing data demonstrated consistent taxonomic distinction from all negative or potential contamination controls (P&#xa0;= .024, PERMANOVA). Classification from contaminant filtered data identified a distinct taxonomic makeup among term and preterm cohorts when compared with contaminant controls (false discovery rate <0.05).<br><br>CONCLUSION: Presumptively intact placental microbes are visualized as low-abundance, low-biomass and sparse populations within the placenta regardless of gestational age and mode of delivery. Their taxonomic makeup is distinct from contamination controls. These findings further support several previously published findings, including our own, which have used metagenomics to characterize low-abundance and low-biomass microbial communities in the placenta.}, }
@article {pmid31047664, year = {2019}, author = {Chetwynd, AJ and Ogilvie, LA and Nzakizwanayo, J and Pazdirek, F and Hoch, J and Dedi, C and Gilbert, D and Abdul-Sada, A and Jones, BV and Hill, EM}, title = {The potential of nanoflow liquid chromatography-nano electrospray ionisation-mass spectrometry for global profiling the faecal metabolome.}, journal = {Journal of chromatography. A}, volume = {1600}, number = {}, pages = {127-136}, doi = {10.1016/j.chroma.2019.04.028}, pmid = {31047664}, issn = {1873-3778}, support = {G0901553/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Bile Acids and Salts/analysis ; *Chromatography, Liquid ; Eicosanoids/analysis ; Feces/*chemistry ; Female ; Healthy Volunteers ; Humans ; Male ; *Metabolome ; Metabolomics ; Phospholipids/analysis ; Pilot Projects ; *Spectrometry, Mass, Electrospray Ionization ; }, abstract = {Faeces are comprised of a wide array of metabolites arising from the circulatory system as well as the human microbiome. A global metabolite analysis (metabolomics) of faecal extracts offers the potential to uncover new compounds which may be indicative of the onset of bowel diseases such as colorectal cancer (CRC). To date, faecal metabolomics is still in its infancy and the compounds of low abundance present in faecal extracts poorly characterised. In this study, extracts of faeces from healthy subjects were profiled using a sensitive nanoflow-nanospray LC-MS platform which resulted in highly repeatable peak retention times (<2% CV) and intensities (<15% CV). Analysis of the extracts revealed wide coverage of the faecal metabolome including detection of low abundant signalling compounds such as sex steroids and eicosanoids, alongside highly abundant pharmaceuticals and tetrapyrrole metabolites. A small pilot study investigating differences in metabolomics profiles of faecal samples obtained from 7 CRC, 25 adenomatous polyp and 26 healthy groups revealed that secondary bile acids, conjugated androgens, eicosanoids, phospholipids and an unidentified haem metabolite were potential classes of metabolites that discriminated between the CRC and control sample groups. However, much larger follow up studies are needed to confirm which components of the faecal metabolome are associated with actual CRC disease rather than dietary influences. This study reveals the potential of nanospray-nanoflow LC-MS profiling of faecal samples from large scale cohort studies for uncovering the role of the faecal metabolome in colorectal disease formation.}, }
@article {pmid31046835, year = {2019}, author = {Sharma, A and Richardson, M and Cralle, L and Stamper, CE and Maestre, JP and Stearns-Yoder, KA and Postolache, TT and Bates, KL and Kinney, KA and Brenner, LA and Lowry, CA and Gilbert, JA and Hoisington, AJ}, title = {Longitudinal homogenization of the microbiome between both occupants and the built environment in a cohort of United States Air Force Cadets.}, journal = {Microbiome}, volume = {7}, number = {1}, pages = {70}, pmid = {31046835}, issn = {2049-2618}, mesh = {Bacteria/classification/isolation &amp; purification ; *Built Environment ; Cohort Studies ; Diet ; *Environmental Microbiology ; Female ; Gastrointestinal Microbiome ; *Housing ; Humans ; Longitudinal Studies ; Male ; *Microbiota ; *Military Personnel ; RNA, Ribosomal, 16S ; Skin/microbiology ; United States ; Young Adult ; }, abstract = {BACKGROUND: The microbiome of the built environment has important implications for human health and wellbeing; however, bidirectional exchange of microbes between occupants and surfaces can be confounded by lifestyle, architecture, and external environmental exposures. Here, we present a longitudinal study of United States Air Force Academy cadets (n = 34), which have substantial homogeneity in lifestyle, diet, and age, all factors that influence the human microbiome. We characterized bacterial communities associated with (1) skin and gut samples from roommate pairs, (2) four built environment sample locations inside the pairs' dormitory rooms, (3) four built environment sample locations within shared spaces in the dormitory, and (4) room-matched outdoor samples from the window ledge of their rooms.<br><br>RESULTS: We analyzed 2,170 samples, which generated 21,866 unique amplicon sequence variants. Linear convergence of microbial composition and structure was observed between an occupants' skin and the dormitory surfaces that were only used by that occupant (i.e., desk). Conversely, bacterial community beta diversity (weighted Unifrac) convergence between the skin of both roommates and the shared dormitory floor between the two cadet's beds was not seen across the entire study population. The sampling period included two semester breaks in which the occupants vacated their rooms; upon their return, the beta diversity similarity between their skin and the surfaces had significantly decreased compared to before the break (p&#x2009;<&#x2009;0.05). There was no apparent convergence between the gut and building microbiota, with the exception of communal bathroom door-handles, which suggests that neither co-occupancy, diet, or lifestyle homogenization had a significant impact on gut microbiome similarity between these cadets over the observed time frame. As a result, predictive classifier models were able to identify an individual more accurately based on the gut microbiota (74%) compared to skin (51%).<br><br>CONCLUSIONS: To the best of our knowledge, this is the first study to show an increase in skin microbial similarity of two individuals who start living together for the first time and who are not genetically related or romantically involved. Cohabitation was significantly associated with increased skin microbiota similarity but did not significantly influence the gut microbiota. Following a departure from the occupied space of several weeks, the skin microbiota, but not the gut microbiota, showed a significant reduction in similarity relative to the building. Overall, longitudinal observation of these dynamics enables us to dissect the influence of occupation, diet, and lifestyle factors on occupant and built environment microbial ecology.}, }
@article {pmid31042284, year = {2019}, author = {Vangay, P and Hillmann, BM and Knights, D}, title = {Microbiome Learning Repo (ML Repo): A public repository of microbiome regression and classification tasks.}, journal = {GigaScience}, volume = {8}, number = {5}, pages = {}, pmid = {31042284}, issn = {2047-217X}, support = {R01 AI121383/NIAID NIH HHS/National Institute of Allergy and Infectious Diseases Extramural Activities/United States ; }, mesh = {Algorithms ; *Databases, Genetic ; Humans ; Machine Learning ; Microbiota/*genetics ; *Software ; }, abstract = {The use of machine learning in high-dimensional biological applications, such as the human microbiome, has grown exponentially in recent years, but algorithm developers often lack the domain expertise required for interpretation and curation of the heterogeneous microbiome datasets. We present Microbiome Learning Repo (ML Repo, available at https://knights-lab.github.io/MLRepo/), a public, web-based repository of 33 curated classification and regression tasks from 15 published human microbiome datasets. We highlight the use of ML Repo in several use cases to demonstrate its wide application, and we expect it to be an important resource for algorithm developers.}, }
@article {pmid31028005, year = {2019}, author = {Zhao, S and Lieberman, TD and Poyet, M and Kauffman, KM and Gibbons, SM and Groussin, M and Xavier, RJ and Alm, EJ}, title = {Adaptive Evolution within Gut Microbiomes of Healthy People.}, journal = {Cell host &amp; microbe}, volume = {25}, number = {5}, pages = {656-667.e8}, pmid = {31028005}, issn = {1934-6069}, support = {P30 DK043351/DK/NIDDK NIH HHS/United States ; }, mesh = {*Adaptation, Biological ; Adult ; Bacteroides fragilis/*genetics/*growth &amp; development ; Female ; *Gastrointestinal Microbiome ; Genetics, Population ; Healthy Volunteers ; Humans ; Male ; Metagenomics ; *Microbiota ; Mutation ; Selection, Genetic ; Young Adult ; }, abstract = {Natural selection shapes bacterial evolution in all environments. However, the extent to which commensal bacteria diversify and adapt within the human gut remains unclear. Here, we combine culture-based population genomics and metagenomics to investigate the within-microbiome evolution of Bacteroides fragilis. We find that intra-individual B. fragilis populations contain substantial de novo nucleotide and mobile element diversity, preserving years of within-person history. This history reveals multiple signatures of within-person adaptation, including parallel evolution in sixteen genes. Many of these genes are implicated in cell-envelope biosynthesis and polysaccharide utilization. Tracking evolutionary trajectories using near-daily metagenomic sampling, we find evidence for years-long coexistence in one subject despite adaptive dynamics. We used public metagenomes to investigate one adaptive mutation common in our cohort and found that it emerges frequently in Western, but not Chinese, microbiomes. Collectively, these results demonstrate that B. fragilis adapts within individual microbiomes, pointing to factors that promote long-term gut colonization.}, }
@article {pmid31024514, year = {2019}, author = {Raju, SC and Lagström, S and Ellonen, P and de Vos, WM and Eriksson, JG and Weiderpass, E and Rounge, TB}, title = {Gender-Specific Associations Between Saliva Microbiota and Body Size.}, journal = {Frontiers in microbiology}, volume = {10}, number = {}, pages = {767}, pmid = {31024514}, issn = {1664-302X}, abstract = {OBJECTIVE: The human intestinal microbiota likely play an important role in the development of overweight and obesity. However, the associations between saliva microbiota and body mass index (BMI) have been sparsely studied. The aim of this study was to identify the associations between saliva microbiota and body size in Finnish children.<br><br>METHODS: The saliva microbiota of 900 Finnish children, aged 11-14 years with measured height and weight, was characterized using 16S rRNA (V3-V4) sequencing.<br><br>RESULTS: The core saliva microbiota consisted of 14 genera that were present in more than 95% of the Finnish children. The saliva microbiota profiles were gender-specific with higher alpha-diversity in boys than girls and significant differences between the genders in community composition and abundances. Alpha-diversity differed between normal weight and overweight girls and between normal weight and obese boys. The composition was dissimilar between normal weight and obese girls, but not in boys. The relative abundance profiles differed according to body size. Decrease in commensal saliva bacteria were observed in all the body sizes when compared to normal weight children. Notably, the relative abundance of bacteria related to, Veillonella, Prevotella, Selenomonas, and Streptococcus was reduced in obese children.<br><br>CONCLUSION: Saliva microbiota diversity and composition were significantly associated with body size and gender in Finnish children. Body size-specific saliva microbiota profiles open new avenues for studying the potential roles of microbiota in weight development and management.}, }
@article {pmid31021803, year = {2019}, author = {Wassan, JT and Wang, H and Browne, F and Zheng, H}, title = {Phy-PMRFI: Phylogeny-Aware Prediction of Metagenomic Functions Using Random Forest Feature Importance.}, journal = {IEEE transactions on nanobioscience}, volume = {18}, number = {3}, pages = {273-282}, doi = {10.1109/TNB.2019.2912824}, pmid = {31021803}, issn = {1558-2639}, mesh = {Algorithms ; Databases, Genetic ; *Decision Trees ; High-Throughput Nucleotide Sequencing ; Humans ; Metagenome/*genetics ; *Metagenomics/classification/methods ; Microbiota/genetics ; Pharynx/microbiology ; Phylogeny ; *Support Vector Machine ; }, abstract = {High-throughput sequencing techniques have accelerated functional metagenomics studies through the generation of large volumes of omics data. The integration of these data using computational approaches is potentially useful for predicting metagenomic functions. Machine learning (ML) models can be trained using microbial features which are then used to classify microbial data into different functional classes. For example, ML analyses over the human microbiome data has been linked to the prediction of important biological states. For analysing omics data, integrating abundance count of taxonomical features with their biological relationships is important. These relationships can potentially be uncovered from the phylogenetic tree of microbial taxa. In this paper, we propose a novel integrative framework Phy-PMRFI. This framework is driven by the phylogeny-based modeling of omics data to predict metagenomic functions using important features selected by a random forest importance (RFI) strategy. The proposed framework integrates the underlying phylogenetic tree information with abundance measures of microbial species (features) by creating a novel phylogeny and abundance aware matrix structure (PAAM). Phy-PMRFI progresses by ranking the microbial features using an RFI measure. This is then used as input for microbiome classification. The resultant feature set enhances the performance of the state-of-art methods such as support vector machines. Our proposed integrative framework also outperforms the state-of-the-art pipeline of phylogenetic isometric log-ratio transform (PhILR) and MetaPhyl. Prediction accuracy of 90 % is obtained with Phy-PMRFI over human throat microbiome in comparison to other approaches of PhILR with 53% and MetaPhyl with 71% accuracy.}, }
@article {pmid31009573, year = {2019}, author = {Zhang, X and Figeys, D}, title = {Perspective and Guidelines for Metaproteomics in Microbiome Studies.}, journal = {Journal of proteome research}, volume = {18}, number = {6}, pages = {2370-2380}, doi = {10.1021/acs.jproteome.9b00054}, pmid = {31009573}, issn = {1535-3907}, support = {MOP-114872//CIHR/Canada ; }, mesh = {Computational Biology/methods ; Dysbiosis/genetics/microbiology ; Gastrointestinal Microbiome/*genetics ; Humans ; Metagenome/*genetics ; Metagenomics/*methods ; Proteomics/*methods ; }, abstract = {The microbiome is emerging as a prominent factor affecting human health, and its dysbiosis is associated with various diseases. Compositional profiling of microbiome is increasingly being supplemented with functional characterization. Metaproteomics is intrinsically focused on functional changes and therefore will be an important tool in those studies of the human microbiome. In the past decade, development of new experimental and bioinformatic approaches for metaproteomics has enabled large-scale human metaproteomic studies. However, challenges still exist, and there remains a lack of standardizations and guidelines for properly performing metaproteomic studies on human microbiome. Herein, we provide a perspective of recent developments, the challenges faced, and the future directions of metaproteomics and its applications. In addition, we propose a set of guidelines/recommendations for performing and reporting the results from metaproteomic experiments for the study of human microbiomes. We anticipate that these guidelines will be optimized further as more metaproteomic questions are raised and addressed, and metaproteomic applications are published, so that they are eventually recognized and applied in the field.}, }
@article {pmid31009405, year = {2019}, author = {Holster, S and Lindqvist, CM and Repsilber, D and Salonen, A and de Vos, WM and König, J and Brummer, RJ}, title = {The Effect of Allogenic Versus Autologous Fecal Microbiota Transfer on Symptoms, Visceral Perception and Fecal and Mucosal Microbiota in Irritable Bowel Syndrome: A Randomized Controlled Study.}, journal = {Clinical and translational gastroenterology}, volume = {10}, number = {4}, pages = {e00034}, pmid = {31009405}, issn = {2155-384X}, mesh = {Adult ; Fecal Microbiota Transplantation/*methods ; Feces/*microbiology ; Female ; Gastrointestinal Microbiome/*immunology ; Humans ; Irritable Bowel Syndrome/complications/immunology/microbiology/*therapy ; Male ; Middle Aged ; Pain Measurement ; Transplantation, Autologous/methods ; Transplantation, Homologous/methods ; Treatment Outcome ; Visceral Pain/diagnosis/etiology/*therapy ; }, abstract = {OBJECTIVES: Fecal microbiota transfer (FMT) is suggested as a potential treatment for patients with irritable bowel syndrome (IBS). We aimed to study the effect of allogenic and autologous FMT on IBS symptoms, visceral sensitivity, and compositional changes in fecal and mucosa-adherent microbiota.<br><br>METHODS: Seventeen patients with IBS were randomized either to receive fecal material from a healthy donor (allogenic) or to receive their own fecal material (autologous). The fecal material was administered into the cecum by whole colonoscopy after bowel cleansing.<br><br>RESULTS: No significant differences were found between the allogenic and the autologous FMT regarding symptom scores. However, symptom scores of patients receiving allogenic fecal material significantly decreased after FMT compared with baseline (P = 0.02), which was not the case in the autologous group (P = 0.16). Visceral sensitivity was not affected except for a small beneficial effect on urge scores in the autologous group (P < 0.05). While both fecal and mucosa-adherent microbiota of some patients shifted to their respective donor's fecal microbiota, some patients showed no relevant microbial changes after allogenic FMT. Large compositional shifts in fecal and mucosa-adherent microbiota also occurred in the autologous group.<br><br>CONCLUSIONS: This study showed that a single FMT by colonoscopy may have beneficial effects in IBS; however, the allogenic fecal material was not superior to the autologous fecal material. This suggests that bowel cleansing prior to the colonoscopy and/or processing of the fecal material as part of the FMT routine contribute to symptoms and gut microbiota composition changes in IBS.}, }
@article {pmid31005411, year = {2019}, author = {Hollister, EB and Oezguen, N and Chumpitazi, BP and Luna, RA and Weidler, EM and Rubio-Gonzales, M and Dahdouli, M and Cope, JL and Mistretta, TA and Raza, S and Metcalf, GA and Muzny, DM and Gibbs, RA and Petrosino, JF and Heitkemper, M and Savidge, TC and Shulman, RJ and Versalovic, J}, title = {Leveraging Human Microbiome Features to Diagnose and Stratify Children with Irritable Bowel Syndrome.}, journal = {The Journal of molecular diagnostics : JMD}, volume = {21}, number = {3}, pages = {449-461}, pmid = {31005411}, issn = {1943-7811}, support = {U01 AI124290/AI/NIAID NIH HHS/United States ; K23 DK101688/DK/NIDDK NIH HHS/United States ; R01 NR013497/NR/NINR NIH HHS/United States ; UH3 DK083990/DK/NIDDK NIH HHS/United States ; R03 DK117219/DK/NIDDK NIH HHS/United States ; R01 NR005337/NR/NINR NIH HHS/United States ; P30 DK056338/DK/NIDDK NIH HHS/United States ; RC2 NR011959/NR/NINR NIH HHS/United States ; U01 CA170930/CA/NCI NIH HHS/United States ; U54 HG004973/HG/NHGRI NIH HHS/United States ; R01 AT004326/AT/NCCIH NIH HHS/United States ; R21 DK096323/DK/NIDDK NIH HHS/United States ; }, mesh = {Abdominal Pain/etiology/microbiology ; Bacteria/genetics ; Case-Control Studies ; Child ; Feces/microbiology ; Female ; Gastrointestinal Tract/microbiology ; Genomics ; Humans ; Irritable Bowel Syndrome/complications/*microbiology ; Male ; Metabolome ; *Microbiota ; Multivariate Analysis ; Principal Component Analysis ; Statistics, Nonparametric ; }, abstract = {Accurate diagnosis and stratification of children with irritable bowel syndrome (IBS) remain challenging. Given the central role of recurrent abdominal pain in IBS, we evaluated the relationships of pediatric IBS and abdominal pain with intestinal microbes and fecal metabolites using a comprehensive clinical characterization and multiomics strategy. Using rigorous clinical phenotyping, we identified preadolescent children (aged 7 to 12 years) with Rome III IBS (n = 23) and healthy controls (n = 22) and characterized their fecal microbial communities using whole-genome shotgun metagenomics and global unbiased fecal metabolomic profiling. Correlation-based approaches and machine learning algorithms identified associations between microbes, metabolites, and abdominal pain. IBS cases differed from controls with respect to key bacterial taxa (eg, Flavonifractor plautii and Lachnospiraceae bacterium 7_1_58FAA), metagenomic functions (eg, carbohydrate metabolism and amino acid metabolism), and higher-order metabolites (eg, secondary bile acids, sterols, and steroid-like compounds). Significant associations between abdominal pain frequency and severity and intestinal microbial features were identified. A random forest classifier built on metagenomic and metabolic markers successfully distinguished IBS cases from controls (area under the curve, 0.93). Leveraging multiple lines of evidence, intestinal microbes, genes/pathways, and metabolites were associated with IBS, and these features were capable of distinguishing children with IBS from healthy children. These multi-omics features, and their links to childhood IBS coupled with nutritional interventions, may lead to new microbiome-guided diagnostic and therapeutic strategies.}, }
@article {pmid31003081, year = {2019}, author = {Díez López, C and Vidaki, A and Ralf, A and Montiel González, D and Radjabzadeh, D and Kraaij, R and Uitterlinden, AG and Haas, C and Lao, O and Kayser, M}, title = {Novel taxonomy-independent deep learning microbiome approach allows for accurate classification of different forensically relevant human epithelial materials.}, journal = {Forensic science international. Genetics}, volume = {41}, number = {}, pages = {72-82}, doi = {10.1016/j.fsigen.2019.03.015}, pmid = {31003081}, issn = {1878-0326}, mesh = {*Deep Learning ; Female ; Forensic Genetics/methods ; *High-Throughput Nucleotide Sequencing ; Humans ; Male ; *Microbiota ; RNA, Ribosomal, 16S/*genetics ; Saliva/microbiology ; *Sequence Analysis, RNA ; Skin/microbiology ; Vagina/microbiology ; }, abstract = {Correct identification of different human epithelial materials such as from skin, saliva and vaginal origin is relevant in forensic casework as it provides crucial information for crime reconstruction. However, the overlap in human cell type composition between these three epithelial materials provides challenges for their differentiation and identification when using previously proposed human cell biomarkers, while their microbiota composition largely differs. By using validated 16S rRNA gene massively parallel sequencing data from the Human Microbiome Project of 1636 skin, oral and vaginal samples, 50 taxonomy-independent deep learning networks were trained to classify these three tissues. Validation testing was performed in de-novo generated high-throughput 16S rRNA gene sequencing data using the Ion Torrent[™] Personal Genome Machine from 110 test samples: 56 hand skin, 31 saliva and 23 vaginal secretion specimens. Body-site classification accuracy of these test samples was very high as indicated by AUC values of 0.99 for skin, 0.99 for oral, and 1 for vaginal secretion. Misclassifications were limited to 3 (5%) skin samples. Additional forensic validation testing was performed in mock casework samples by de-novo high-throughput sequencing of 19 freshly-prepared samples and 22 samples aged for 1 up to 7.6 years. All of the 19 fresh and 20 (91%) of the 22 aged mock casework samples were correctly tissue-type classified. Moreover, comparing the microbiome results with outcomes from previous human mRNA-based tissue identification testing in the same 16 aged mock casework samples reveals that our microbiome approach performs better in 12 (75%), similarly in 2 (12.5%), and less good in 2 (12.5%) of the samples. Our results demonstrate that this new microbiome approach allows for accurate tissue-type classification of three human epithelial materials of skin, oral and vaginal origin, which is highly relevant for future forensic investigations.}, }
@article {pmid30994455, year = {2019}, author = {Inkpen, SA}, title = {Health, ecology and the microbiome.}, journal = {eLife}, volume = {8}, number = {}, pages = {}, pmid = {30994455}, issn = {2050-084X}, mesh = {*Ecosystem ; *Health ; *Host Microbial Interactions ; Humans ; *Microbiota ; }, abstract = {Advances in microbiomics have changed the way in which many researchers think about health and disease. These changes have also raised a number of philosophical questions around these topics, such as the types of living systems to which these concepts can be applied. Here, I discuss the human microbiome from two perspectives: the first treats the microbiome as part of a larger system that includes the human; the second treats the microbiome as an independent ecosystem that provides services to humans. Drawing on the philosophy of medicine and ecology, I explore two questions: i) how can we make sense of disease and dysfunction in these two perspectives? ii) are these two perspectives complimentary or do they compete with each other?}, }
@article {pmid30994187, year = {2019}, author = {Wang, T and Yang, C and Zhao, H}, title = {Prediction analysis for microbiome sequencing data.}, journal = {Biometrics}, volume = {75}, number = {3}, pages = {875-884}, doi = {10.1111/biom.13061}, pmid = {30994187}, issn = {1541-0420}, mesh = {Algorithms ; Bacteria/genetics ; Humans ; Likelihood Functions ; Microbiota/*genetics ; Monte Carlo Method ; Regression Analysis ; *Sequence Analysis ; }, abstract = {One goal of human microbiome studies is to relate host traits with human microbiome compositions. The analysis of microbial community sequencing data presents great statistical challenges, especially when the samples have different library sizes and the data are overdispersed with many zeros. To address these challenges, we introduce a new statistical framework, called predictive analysis in metagenomics via inverse regression (PAMIR), to analyze microbiome sequencing data. Within this framework, an inverse regression model is developed for overdispersed microbiota counts given the trait, and then a prediction rule is constructed by taking advantage of the dimension-reduction structure in the model. An efficient Monte Carlo expectation-maximization algorithm is proposed for maximum likelihood estimation. The method is further generalized to accommodate other types of covariates. We demonstrate the advantages of PAMIR through simulations and two real data examples.}, }
@article {pmid30993039, year = {2019}, author = {Garretto, A and Hatzopoulos, T and Putonti, C}, title = {virMine: automated detection of viral sequences from complex metagenomic samples.}, journal = {PeerJ}, volume = {7}, number = {}, pages = {e6695}, pmid = {30993039}, issn = {2167-8359}, abstract = {Metagenomics has enabled sequencing of viral communities from a myriad of different environments. Viral metagenomic studies routinely uncover sequences with no recognizable homology to known coding regions or genomes. Nevertheless, complete viral genomes have been constructed directly from complex community metagenomes, often through tedious manual curation. To address this, we developed the software tool virMine to identify viral genomes from raw reads representative of viral or mixed (viral and bacterial) communities. virMine automates sequence read quality control, assembly, and annotation. Researchers can easily refine their search for a specific study system and/or feature(s) of interest. In contrast to other viral genome detection tools that often rely on the recognition of viral signature sequences, virMine is not restricted by the insufficient representation of viral diversity in public data repositories. Rather, viral genomes are identified through an iterative approach, first omitting non-viral sequences. Thus, both relatives of previously characterized viruses and novel species can be detected, including both eukaryotic viruses and bacteriophages. Here we present virMine and its analysis of synthetic communities as well as metagenomic data sets from three distinctly different environments: the gut microbiota, the urinary microbiota, and freshwater viromes. Several new viral genomes were identified and annotated, thus contributing to our understanding of viral genetic diversity in these three environments.}, }
@article {pmid30992349, year = {2019}, author = {Aleti, G and Baker, JL and Tang, X and Alvarez, R and Dinis, M and Tran, NC and Melnik, AV and Zhong, C and Ernst, M and Dorrestein, PC and Edlund, A}, title = {Identification of the Bacterial Biosynthetic Gene Clusters of the Oral Microbiome Illuminates the Unexplored Social Language of Bacteria during Health and Disease.}, journal = {mBio}, volume = {10}, number = {2}, pages = {}, pmid = {30992349}, issn = {2150-7511}, support = {F32 DE026947/DE/NIDCR NIH HHS/United States ; K99 DE024543/DE/NIDCR NIH HHS/United States ; R00 DE024543/DE/NIDCR NIH HHS/United States ; }, mesh = {Bacteria/genetics/isolation &amp; purification ; Biosynthetic Pathways/*genetics ; Child ; Child, Preschool ; Computational Biology ; Dental Caries/microbiology ; Dysbiosis ; Humans ; Mass Spectrometry ; Metagenome ; *Microbial Interactions ; Microbiota/*genetics ; Mouth/*microbiology ; *Multigene Family ; Periodontitis/microbiology ; Saliva/microbiology ; }, abstract = {Small molecules are the primary communication media of the microbial world. Recent bioinformatic studies, exploring the biosynthetic gene clusters (BGCs) which produce many small molecules, have highlighted the incredible biochemical potential of the signaling molecules encoded by the human microbiome. Thus far, most research efforts have focused on understanding the social language of the gut microbiome, leaving crucial signaling molecules produced by oral bacteria and their connection to health versus disease in need of investigation. In this study, a total of 4,915 BGCs were identified across 461 genomes representing a broad taxonomic diversity of oral bacteria. Sequence similarity networking provided a putative product class for more than 100 unclassified novel BGCs. The newly identified BGCs were cross-referenced against 254 metagenomes and metatranscriptomes derived from individuals either with good oral health or with dental caries or periodontitis. This analysis revealed 2,473 BGCs, which were differentially represented across the oral microbiomes associated with health versus disease. Coabundance network analysis identified numerous inverse correlations between BGCs and specific oral taxa. These correlations were present in healthy individuals but greatly reduced in individuals with dental caries, which may suggest a defect in colonization resistance. Finally, corroborating mass spectrometry identified several compounds with homology to products of the predicted BGC classes. Together, these findings greatly expand the number of known biosynthetic pathways present in the oral microbiome and provide an atlas for experimental characterization of these abundant, yet poorly understood, molecules and socio-chemical relationships, which impact the development of caries and periodontitis, two of the world's most common chronic diseases.IMPORTANCE The healthy oral microbiome is symbiotic with the human host, importantly providing colonization resistance against potential pathogens. Dental caries and periodontitis are two of the world's most common and costly chronic infectious diseases and are caused by a localized dysbiosis of the oral microbiome. Bacterially produced small molecules, often encoded by BGCs, are the primary communication media of bacterial communities and play a crucial, yet largely unknown, role in the transition from health to dysbiosis. This study provides a comprehensive mapping of the BGC repertoire of the human oral microbiome and identifies major differences in health compared to disease. Furthermore, BGC representation and expression is linked to the abundance of particular oral bacterial taxa in health versus dental caries and periodontitis. Overall, this study provides a significant insight into the chemical communication network of the healthy oral microbiome and how it devolves in the case of two prominent diseases.}, }
@article {pmid30981803, year = {2019}, author = {Parida, S and Sharma, D}, title = {The power of small changes: Comprehensive analyses of microbial dysbiosis in breast cancer.}, journal = {Biochimica et biophysica acta. Reviews on cancer}, volume = {1871}, number = {2}, pages = {392-405}, pmid = {30981803}, issn = {1879-2561}, support = {R01 CA204555/CA/NCI NIH HHS/United States ; R01 CA204555/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Breast Neoplasms/*microbiology ; *Dysbiosis ; Female ; Humans ; }, abstract = {Disparate occurrence of breast cancer remains an intriguing question since only a subset of women with known risk factors develop cancer. Recent studies suggest an active role of local and distant microbiota in breast cancer initiation, progression, and overall prognosis. A dysbiotic microbiota predisposes the body to develop cancer by inducing genetic instability, initiating DNA damage and proliferation of the damaged progeny, eliciting favorable immune response, metabolic dysregulation and altered response to therapy. In this review, we present our analyses of the existing datasets and discuss the local dysbiosis observed in breast cancer patients and different aspects of breast carcinogenesis that can be potentially influenced by local breast microbiota. Striking differences between microbial community compositions in breast of cancer patients compared to healthy individuals were noted. Differences in microbiome were also apparent between benign and malignant disease and between nipple aspirate fluid of healthy individuals and breast survivors. We also discuss the identification of distinct bacterial, fungal, viral as well as parasite signatures for breast cancer. These microbes are capable of producing numerous secondary metabolites that can act as signaling mediators effecting breast cancer progression. We review how microbes potentially alter response to therapy affecting drug metabolism, pharmacokinetics, anti-tumor effects and toxicity. In conclusion, breast harbors a community of microbes that can communicate with the host cells inducing downstream signaling pathways and modulating various aspects of breast cancer growth and metastatic progression and an improved understanding of microbial dysbiosis can potentially reduce breast cancer risk and improve outcomes of breast cancer patients. The human microbiome, now referred to as, the "forgotten organ" contains a metagenome that is 100-fold more diverse compared to the human genome, thereby, is critically associated with human health [1,2]. With the revelations of the human microbiome project and advent of deep sequencing techniques, a plethora of information has been acquired in recent years. Body sites like stomach, bladder and lungs, once thought to be sterile, are now known to harbor millions of indigenous microbial species. Approximately 80% of the healthy microbiome consists of Firmicutes and Bacteroidetes accompanied by Verrucomicrobia, Actinobacteria, Proteobacteria, Tenericutes and Cyanobacteria [2-7]. The role of microbiome in diabetes, obesity and even neurodegenerative diseases was greatly appreciated in the last decade [1,7-14] and now it has been established that microbiome significantly contributes to many organ specific cancers [1,15,16].}, }
@article {pmid30979072, year = {2019}, author = {Lerner, A and Shoenfeld, Y and Matthias, T}, title = {Probiotics: If It Does Not Help It Does Not Do Any Harm. Really?.}, journal = {Microorganisms}, volume = {7}, number = {4}, pages = {}, pmid = {30979072}, issn = {2076-2607}, abstract = {Probiotics per definition should have beneficial effects on human health, and their consumption has tremendously increased in the last decades. In parallel, the amount of published material and claims for their beneficial efficacy soared continuously. Recently, multiple systemic reviews, meta-analyses, and expert opinions expressed criticism on their claimed effects and safety. The present review describes the dark side of the probiotics, in terms of problematic research design, incomplete reporting, lack of transparency, and under-reported safety. Highlighted are the potential virulent factors and the mode of action in the intestinal lumen, risking the physiological microbiome equilibrium. Finally, regulatory topics are discussed to lighten the heterogeneous guidelines applied worldwide. The shift in the scientific world towards a better understanding of the human microbiome, before consumption of the probiotic cargo, is highly endorsed. It is hoped that better knowledge will extend the probiotic repertoire, re-confirm efficacy or safety, establish their efficacy and substantiate their beneficial effects.}, }
@article {pmid30976019, year = {2019}, author = {Jeong, H and Arif, B and Caetano-Anollés, G and Kim, KM and Nasir, A}, title = {Horizontal gene transfer in human-associated microorganisms inferred by phylogenetic reconstruction and reconciliation.}, journal = {Scientific reports}, volume = {9}, number = {1}, pages = {5953}, pmid = {30976019}, issn = {2045-2322}, mesh = {Bacteria/classification/*genetics/isolation &amp; purification ; Computational Biology/*methods ; Evolution, Molecular ; *Gene Transfer, Horizontal ; *Genes, Bacterial ; *Genome, Bacterial ; Humans ; Models, Genetic ; *Phylogeny ; }, abstract = {Horizontal gene transfer (HGT) is widespread in the evolution of prokaryotes, especially those associated with the human body. Here, we implemented large-scale gene-species phylogenetic tree reconstructions and reconciliations to identify putative HGT-derived genes in the reference genomes of microbiota isolated from six major human body sites by the NIH Human Microbiome Project. Comparisons with a control group representing microbial genomes from diverse natural environments indicated that HGT activity increased significantly in the genomes of human microbiota, which is confirmatory of previous findings. Roughly, more than half of total genes in the genomes of human-associated microbiota were transferred (donated or received) by HGT. Up to 60% of the detected HGTs occurred either prior to the colonization of the human body or involved bacteria residing in different body sites. The latter could suggest 'genetic crosstalk' and movement of bacterial genes within the human body via hitherto poorly understood mechanisms. We also observed that HGT activity increased significantly among closely-related microorganisms and especially when they were united by physical proximity, suggesting that the 'phylogenetic effect' can significantly boost HGT activity. Finally, we identified several core and widespread genes least influenced by HGT that could become useful markers for building robust 'trees of life' and address several outstanding technical challenges to improve the phylogeny-based genome-wide HGT detection method for future applications.}, }
@article {pmid30959425, year = {2019}, author = {Shetty, SA and Smidt, H and de Vos, WM}, title = {Reconstructing functional networks in the human intestinal tract using synthetic microbiomes.}, journal = {Current opinion in biotechnology}, volume = {58}, number = {}, pages = {146-154}, doi = {10.1016/j.copbio.2019.03.009}, pmid = {30959425}, issn = {1879-0429}, mesh = {*Gastrointestinal Microbiome ; Humans ; Intestines ; }, abstract = {The human intestinal tract harbors one of the most densely populated and open microbial ecosystems. The application of multi-omics approaches has provided insight into a wide array of complex interactions between the various groups of mainly anaerobic colonic microbes as well as the host-microbe dialogue. Integration of multi-omics techniques in cultivation based experiments that vary in complexity from monocultures to synthetic microbial communities identified key metabolic players in the trophic interactions as well as their ecological dynamics. A synergy between these approaches will be of utmost importance to reconstruct the functional interaction networks at the ecosystem level within the human intestinal microbiome. The improved understanding of microbiome functioning at ecosystem level will further aid in developing better predictive models and design of effective microbiome modulation strategies for health benefits.}, }
@article {pmid30958298, year = {2019}, author = {Algazina, T and Yermekbayeva, B and Batpenova, G and Kushugulova, A}, title = {FEATURES OF MICROBIOTA IN PSORIATIC DISEASE: FROM SKIN AND GUT PERSPECTIVES (REVIEW).}, journal = {Georgian medical news}, volume = {}, number = {287}, pages = {98-104}, pmid = {30958298}, issn = {1512-0112}, mesh = {Arthritis, Psoriatic/*microbiology/pathology ; Dermatitis, Atopic ; Humans ; *Microbiota ; Psoriasis/*microbiology/pathology ; Skin/*microbiology/pathology ; }, abstract = {Psoriatic disease is a chronic inflammatory disease characterized by skin lesions. Psoriasis development has been associated both with genetic and environmental factors. Though skin and gut microbiota has been implicated in number of pathologies including atopic dermatitis, inflammatory bowel disease, Crohn's disease, allergy, and obesity, its role has been poorly studied in psoriatic disease, which incorporates both psoriasis and psoriatic arthritis. This literature review summarizes the most recent and major findings on microbiota features in psoriatic disease. Despite conflicting findings, psoriasis patients were frequently found to have distinct microbial composition in both skin and guts especially in the major bacterial phyla, Firmicutes, Bacteroidetes, and genus Akkermansia. Furthermore, bacterial DNA has been found in psoriatic patients both locally and systemically, and altogether suggesting a crucial role of bacteria in psoriatic disease and future studies in this field.}, }
@article {pmid30955503, year = {2019}, author = {Checinska Sielaff, A and Urbaniak, C and Mohan, GBM and Stepanov, VG and Tran, Q and Wood, JM and Minich, J and McDonald, D and Mayer, T and Knight, R and Karouia, F and Fox, GE and Venkateswaran, K}, title = {Characterization of the total and viable bacterial and fungal communities associated with the International Space Station surfaces.}, journal = {Microbiome}, volume = {7}, number = {1}, pages = {50}, pmid = {30955503}, issn = {2049-2618}, mesh = {Bacteria/*classification/genetics/isolation &amp; purification ; Confined Spaces ; Environmental Microbiology ; Fungi/*classification/genetics/isolation &amp; purification ; Humans ; Microbiological Techniques/*methods ; Phylogeny ; Sequence Analysis, DNA/*methods ; Spacecraft ; Weightlessness ; }, abstract = {BACKGROUND: The International Space Station (ISS) is a closed system inhabited by microorganisms originating from life support systems, cargo, and crew that are exposed to unique selective pressures such as microgravity. To date, mandatory microbial monitoring and observational studies of spacecraft and space stations have been conducted by traditional culture methods, although it is known that many microbes cannot be cultured with standard techniques. To fully appreciate the true number and diversity of microbes that survive in the ISS, molecular and culture-based methods were used to assess microbial communities on ISS surfaces. Samples were taken at eight pre-defined locations during three flight missions spanning 14 months and analyzed upon return to Earth.<br><br>RESULTS: The cultivable bacterial and fungal population ranged from 10[4] to 10[9] CFU/m[2] depending on location and consisted of various bacterial (Actinobacteria, Firmicutes, and Proteobacteria) and fungal (Ascomycota and Basidiomycota) phyla. Amplicon sequencing detected more bacterial phyla when compared to the culture-based analyses, but both methods identified similar numbers of fungal phyla. Changes in bacterial and fungal load (by culture and qPCR) were observed over time but not across locations. Bacterial community composition changed over time, but not across locations, while fungal community remained the same between samplings and locations. There were no significant differences in community composition and richness after propidium monoazide sample treatment, suggesting that the analyzed DNA was extracted from intact/viable organisms. Moreover, approximately 46% of intact/viable bacteria and 40% of intact/viable fungi could be cultured.<br><br>CONCLUSIONS: The results reveal a diverse population of bacteria and fungi on ISS environmental surfaces that changed over time but remained similar between locations. The dominant organisms are associated with the human microbiome and may include opportunistic pathogens. This study provides the first comprehensive catalog of both total and intact/viable bacteria and fungi found on surfaces in closed space systems and can be used to help develop safety measures that meet NASA requirements for deep space human habitation. The results of this study can have significant impact on our understanding of other confined built environments on the Earth such as clean rooms used in the pharmaceutical and medical industries.}, }
@article {pmid30946154, year = {2019}, author = {Sessa, L and Reddel, S and Manno, E and Quagliariello, A and Cotugno, N and Del Chierico, F and Amodio, D and Capponi, C and Leone, F and Bernardi, S and Rossi, P and Putignani, L and Palma, P}, title = {Distinct gut microbiota profile in antiretroviral therapy-treated perinatally HIV-infected patients associated with cardiac and inflammatory biomarkers.}, journal = {AIDS (London, England)}, volume = {33}, number = {6}, pages = {1001-1011}, doi = {10.1097/QAD.0000000000002131}, pmid = {30946154}, issn = {1473-5571}, mesh = {Adolescent ; Adult ; Anti-Retroviral Agents/therapeutic use ; Bacteria/classification/genetics ; Bacterial Translocation ; Cardiovascular Diseases/*pathology ; Child ; Child, Preschool ; Cross-Sectional Studies ; Dysbiosis/*complications ; Female ; *Gastrointestinal Microbiome ; HIV Infections/*complications/*drug therapy ; Humans ; Inflammation/*pathology ; Male ; Metagenomics ; *Microbiota ; Young Adult ; }, abstract = {OBJECTIVE: Persistent inflammation and higher risk to develop cardiovascular diseases still represent a major complication for HIV-infected patients despite effective antiretroviral therapy (ART). We investigated the correlation between the gut microbiota profile, markers of inflammation, vascular endothelial activation (VEA) and microbial translocation (MT) in perinatally HIV-infected patients (PHIV) under ART.<br><br>DESIGN: Cross-sectional study including 61 ART-treated PHIV (age range 3-30 years old) and 71 age-matched healthy controls. Blood and stool sample were collected at the same time and analyzed for gut microbiota composition and plasma biomarkers.<br><br>METHODS: Gut microbiota composition was determined by 16S rRNA targeted-metagenomics. Soluble markers of MT, inflammation and VEA were quantified by ELISA or Luminex assay. Markers of immune activation were analyzed by flow cytometry on CD4 and CD8T cells.<br><br>RESULTS: We identified two distinct gut microbiota profiles (groups A and B) among PHIV. No different clinical parameters (age, sex, ethnicity, clinical class), dietary and sexual habits were found between the groups. The group A showed a relative dominance of Akkermansia muciniphila, whereas gut microbiota of group B was characterized by a higher biodiversity. The analysis of soluble markers revealed a significantly higher level of soluble E-selectine (P&#x200a;=&#x200a;0.0296), intercellular adhesion molecule-1 (P&#x200a;=&#x200a;0.0028), vascular adhesion molecule-1 (P&#x200a;=&#x200a;0.0230), IL-6 (P&#x200a;=&#x200a;0.0247) and soluble CD14 (P&#x200a;=&#x200a;0.0142) in group A compared with group B.<br><br>CONCLUSION: Distinctive gut microbiota profiles are differently associated with inflammation, microbial translocation and VEA. Future studies are needed to understand the role of A. muciniphila and risk to develop cardiovascular diseases in PHIV.}, }
@article {pmid30942867, year = {2019}, author = {Brown, SM and Chen, H and Hao, Y and Laungani, BP and Ali, TA and Dong, C and Lijeron, C and Kim, B and Wultsch, C and Pei, Z and Krampis, K}, title = {MGS-Fast: Metagenomic shotgun data fast annotation using microbial gene catalogs.}, journal = {GigaScience}, volume = {8}, number = {4}, pages = {}, pmid = {30942867}, issn = {2047-217X}, support = {UH3 CA140233/CA/NCI NIH HHS/United States ; UL1 TR000457/TR/NCATS NIH HHS/United States ; G12 MD007599/MD/NIMHD NIH HHS/United States ; R01 AI110372/AI/NIAID NIH HHS/United States ; U54 CA221705/CA/NCI NIH HHS/United States ; UL1 TR002384/TR/NCATS NIH HHS/United States ; R01 CA159036/CA/NCI NIH HHS/United States ; R21 DE025352/DE/NIDCR NIH HHS/United States ; U01 CA182370/CA/NCI NIH HHS/United States ; }, mesh = {Algorithms ; Cloud Computing ; Computational Biology/*methods ; Humans ; Metagenome ; Metagenomics/*methods ; Microbiology ; Microbiota ; Molecular Sequence Annotation ; Reproducibility of Results ; *Software ; Workflow ; }, abstract = {BACKGROUND: Current methods used for annotating metagenomics shotgun sequencing (MGS) data rely on a computationally intensive and low-stringency approach of mapping each read to a generic database of proteins or reference microbial genomes.<br><br>RESULTS: We developed MGS-Fast, an analysis approach for shotgun whole-genome metagenomic data utilizing Bowtie2 DNA-DNA alignment of reads that is an alternative to using the integrated catalog of reference genes database of well-annotated genes compiled from human microbiome data. This method is rapid and provides high-stringency matches (>90% DNA sequence identity) of the metagenomics reads to genes with annotated functions. We demonstrate the use of this method with data from a study of liver disease and synthetic reads, and Human Microbiome Project shotgun data, to detect differentially abundant Kyoto Encyclopedia of Genes and Genomes gene functions in these experiments. This rapid annotation method is freely available as a Galaxy workflow within a Docker image.<br><br>CONCLUSIONS: MGS-Fast can confidently transfer functional annotations from gene databases to metagenomic reads, with speed and accuracy.}, }
@article {pmid30938174, year = {2019}, author = {Sander, MA and Sander, MS and Isaac-Renton, JL and Croxen, MA}, title = {The Cutaneous Microbiome: Implications for Dermatology Practice.}, journal = {Journal of cutaneous medicine and surgery}, volume = {23}, number = {4}, pages = {436-441}, doi = {10.1177/1203475419839939}, pmid = {30938174}, issn = {1615-7109}, mesh = {Genomics ; Humans ; *Microbiota/genetics ; Precision Medicine ; Skin/*microbiology ; Skin Diseases/drug therapy/*microbiology ; }, abstract = {The human integument is inhabited by a vast array of microorganisms known collectively as the cutaneous microbiome. As a result of advances in laboratory science, our understanding of the diversity and complexity of the human microbiome is rapidly evolving. In particular, advances in the field of genomics have enabled the study of the cutaneous microbiome with a hitherto unimaginable level of detail, resulting in a maturation of our understanding of cutaneous health and disease. Herein, we review current microbiology concepts and highlight the key features of recent laboratory advances, particularly with respect to genomics. We provide a summary of new findings related to normal skin flora, interactions between host immunity and microbial communities, and microbial relationships with common skin disorders. Finally, we review the implications for dermatologists.}, }
@article {pmid30937887, year = {2019}, author = {Sharma, A and Buschmann, MM and Gilbert, JA}, title = {Pharmacomicrobiomics: The Holy Grail to Variability in Drug Response?.}, journal = {Clinical pharmacology and therapeutics}, volume = {106}, number = {2}, pages = {317-328}, doi = {10.1002/cpt.1437}, pmid = {30937887}, issn = {1532-6535}, mesh = {*Host Microbial Interactions/drug effects/physiology ; Humans ; *Microbiota/drug effects/physiology ; Pharmaceutical Preparations/*metabolism ; *Pharmacogenetics ; Systems Biology ; }, abstract = {The human body, with 3.0 × 10[13] cells and more than 3.8 × 10[13] microorganisms, has nearly a one-to-one ratio of resident microbes to human cells. Initiatives like the Human Microbiome Project, American Gut, and Flemish Gut have identified associations between microbial taxa and human health. The study of interactions between microbiome and pharmaceutical agents, i.e., pharmacomicrobiomics, has revealed an instrumental role of the microbiome in modulating drug response that alters the therapeutic outcomes. In this review, we present our current comprehension of the relationship of the microbiome, host biology, and pharmaceutical agents such as cardiovascular drugs, analgesics, and chemotherapeutic agents to human disease and treatment outcomes. We also discuss the significance of studying diet-gene-drug interactions and further address the key challenges associated with pharmacomicrobiomics. Finally, we examine proposed models employing systems biology for the application of pharmacomicrobiomics and other -omics data, and provide approaches to elucidate microbiome-drug interactions to improve future translation to personalized medicine.}, }
@article {pmid30935409, year = {2019}, author = {Hamidi, B and Wallace, K and Vasu, C and Alekseyenko, AV}, title = {W[∗]d -test: robust distance-based multivariate analysis of variance.}, journal = {Microbiome}, volume = {7}, number = {1}, pages = {51}, pmid = {30935409}, issn = {2049-2618}, support = {R01 LM012517/LM/NLM NIH HHS/United States ; U54 CA210962/CA/NCI NIH HHS/United States ; U54 CA210963/CA/NCI NIH HHS/United States ; UL1 TR001450/TR/NCATS NIH HHS/United States ; }, mesh = {Computational Biology/*methods ; Computer Simulation ; Humans ; *Microbiota ; Multivariate Analysis ; Software ; }, abstract = {BACKGROUND: Community-wide analyses provide an essential means for evaluation of the effect of interventions or design variables on the composition of the microbiome. Applications of these analyses are omnipresent in microbiome literature, yet some of their statistical properties have not been tested for robustness towards common features of microbiome data. Recently, it has been reported that PERMANOVA can yield wrong results in the presence of heteroscedasticity and unbalanced sample sizes.<br><br>FINDINGS: We develop a method for multivariate analysis of variance, [Formula: see text], based on Welch MANOVA that is robust to heteroscedasticity in the data. We do so by extending a previously reported method that does the same for two-level independent factor variables. Our approach can accommodate multi-level factors, stratification, and multiple post hoc testing scenarios. An R language implementation of the method is available at https://github.com/alekseyenko/WdStar .<br><br>CONCLUSION: Our method resolves potential for confounding of location and dispersion effects in multivariate analyses by explicitly accounting for the differences in multivariate dispersion in the data tested. The methods based on [Formula: see text] have general applicability in microbiome and other 'omics data analyses.}, }
@article {pmid30935126, year = {2019}, author = {Massari, F and Mollica, V and Di Nunno, V and Gatto, L and Santoni, M and Scarpelli, M and Cimadamore, A and Lopez-Beltran, A and Cheng, L and Battelli, N and Montironi, R and Brandi, G}, title = {The Human Microbiota and Prostate Cancer: Friend or Foe?.}, journal = {Cancers}, volume = {11}, number = {4}, pages = {}, pmid = {30935126}, issn = {2072-6694}, abstract = {The human microbiome is gaining increasing attention in the medical community, as knowledge on its role not only in health but also in disease development and response to therapies is expanding. Furthermore, the connection between the microbiota and cancer, especially the link between the gut microbiota and gastrointestinal tumors, is becoming clearer. The interaction between the microbiota and the response to chemotherapies and, more recently, to immunotherapy has been widely studied, and a connection between a peculiar type of microbiota and a better response to these therapies and a different incidence in toxicities has been hypothesized. As knowledge on the gut microbiota increases, interest in the residing microbial population in other systems of our body is also increasing. Consequently, the urinary microbiota is under evaluation for its possible implications in genitourinary diseases, including cancer. Prostate cancer is the most common cancer in the male population; thus, research regarding its etiology and possible factors correlated to disease progression or the response to specific therapies is thriving. This review has the purpose to recollect the current knowledge on the relationship between the human microbiota and prostate cancer.}, }
@article {pmid30935109, year = {2019}, author = {Nava Lara, RA and Aguilera-Mendoza, L and Brizuela, CA and Peña, A and Del Rio, G}, title = {Heterologous Machine Learning for the Identification of Antimicrobial Activity in Human-Targeted Drugs.}, journal = {Molecules (Basel, Switzerland)}, volume = {24}, number = {7}, pages = {}, pmid = {30935109}, issn = {1420-3049}, support = {FOIN-219//Consejo Nacional de Ciencia y Tecnolog&#xed;a/ ; CB-252316//Consejo Nacional de Ciencia y Tecnolog&#xed;a/ ; IG100416//Programa de Apoyo a Proyectos de Investigaci&#xf3;n e Innovaci&#xf3;n Tecnol&#xf3;gica, UNAM, Mexico/ ; IN208014//Programa de Apoyo a Proyectos de Investigaci&#xf3;n e Innovaci&#xf3;n Tecnol&#xf3;gica, UNAM, Mexico/ ; }, mesh = {Anti-Infective Agents/*chemistry/*pharmacology ; Bacteria/drug effects ; *Drug Discovery/methods ; Gastrointestinal Microbiome/drug effects ; Humans ; *Machine Learning ; Microbial Sensitivity Tests ; }, abstract = {The emergence of microbes resistant to common antibiotics represent a current treat to human health. It has been recently recognized that non-antibiotic labeled drugs may promote antibiotic-resistance mechanisms in the human microbiome by presenting a secondary antibiotic activity; hence, the development of computer-assisted procedures to identify antibiotic activity in human-targeted compounds may assist in preventing the emergence of resistant microbes. In this regard, it is worth noting that while most antibiotics used to treat human infectious diseases are non-peptidic compounds, most known antimicrobials nowadays are peptides, therefore all computer-based models aimed to predict antimicrobials either use small datasets of non-peptidic compounds rendering predictions with poor reliability or they predict antimicrobial peptides that are not currently used in humans. Here we report a machine-learning-based approach trained to identify gut antimicrobial compounds; a unique aspect of our model is the use of heterologous training sets, in which peptide and non-peptide antimicrobial compounds were used to increase the size of the training data set. Our results show that combining peptide and non-peptide antimicrobial compounds rendered the best classification of gut antimicrobial compounds. Furthermore, this classification model was tested on the latest human-approved drugs expecting to identify antibiotics with broad-spectrum activity and our results show that the model rendered predictions consistent with current knowledge about broad-spectrum antibiotics. Therefore, heterologous machine learning rendered an efficient computational approach to classify antimicrobial compounds.}, }
@article {pmid30930963, year = {2018}, author = {Jaja-Chimedza, A and Zhang, L and Wolff, K and Graf, BL and Kuhn, P and Moskal, K and Carmouche, R and Newman, S and Salbaum, JM and Raskin, I}, title = {A dietary isothiocyanate-enriched moringa (Moringa oleifera) seed extract improves glucose tolerance in a high-fat-diet mouse model and modulates the gut microbiome.}, journal = {Journal of functional foods}, volume = {47}, number = {}, pages = {376-385}, pmid = {30930963}, issn = {1756-4646}, support = {P20 RR021945/RR/NCRR NIH HHS/United States ; P30 DK072476/DK/NIDDK NIH HHS/United States ; T32 AT004094/AT/NCCIH NIH HHS/United States ; P20 GM103528/GM/NIGMS NIH HHS/United States ; P50 AT002776/AT/NCCIH NIH HHS/United States ; P30 GM118430/GM/NIGMS NIH HHS/United States ; }, abstract = {Moringa oleifera (moringa) has been traditionally used for the treatment of diabetes and in water purification. We previously showed that moringa seed extract (MSE), standardized to its primary bioactive isothiocyanate (MIC-1), modulated inflammatory and antioxidant signaling pathways in vitro. To understand the efficacy and mechanisms of action of MSE in vivo, we incorporated MSE into the diets of normal and obese C57Bl/6J male mice fed a standard low-fat diet or a very high-fat diet for 12 wk, respectively. MSE supplementation resulted in reduced body weight, decreased adiposity, improved glucose tolerance, reduced inflammatory gene expression, and increased antioxidant gene expression. 16S rRNA gene sequencing and quantitative PCR of fecal/cecal samples showed major modulation of the gut microbial community and a significantly reduced bacterial load, similar to an antibiotic response. This suggests that MSE improves metabolic health by its intracellular anti-inflammatory and antioxidant activities, and/or its antibiotic-like restructuring of the gut microbiota.}, }
@article {pmid30930939, year = {2019}, author = {Guo, M and Xu, E and Ai, D}, title = {Inferring Bacterial Infiltration in Primary Colorectal Tumors From Host Whole Genome Sequencing Data.}, journal = {Frontiers in genetics}, volume = {10}, number = {}, pages = {213}, pmid = {30930939}, issn = {1664-8021}, support = {R01 HG006137/HG/NHGRI NIH HHS/United States ; }, abstract = {Colorectal cancer is the third most common cancer worldwide with abysmal survival, thus requiring novel therapy strategies. Numerous studies have frequently observed infiltrating bacteria within the primary tumor tissues derived from patients. These studies have implicated the relative abundance of these bacteria as a contributing factor in tumor progression. Infiltrating bacteria are believed to be among the major drivers of tumorigenesis, progression, and metastasis and, hence, promising targets for new treatments. However, measuring their abundance directly remains challenging. One potential approach is to use the unmapped reads of host whole genome sequencing (hWGS) data, which previous studies have considered as contaminants and discarded. Here, we developed rigorous bioinformatics and statistical procedures to identify tumor-infiltrating bacteria associated with colorectal cancer from such whole genome sequencing data. Our approach used the reads of whole genome sequencing data of colon adenocarcinoma tissues not mapped to the human reference genome, including unmapped paired-end read pairs and single-end reads, the mates of which were mapped. We assembled the unmapped read pairs, remapped all those reads to the collection of human microbiome reference, and then computed their relative abundance of microbes by maximum likelihood (ML) estimation. We analyzed and compared the relative abundance and diversity of infiltrating bacteria between primary tumor tissues and associated normal blood samples. Our results showed that primary tumor tissues contained far more diverse total infiltrating bacteria than normal blood samples. The relative abundance of Bacteroides fragilis, Bacteroides dorei, and Fusobacterium nucleatum was significantly higher in primary colorectal tumors. These three bacteria were among the top ten microbes in the primary tumor tissues, yet were rarely found in normal blood samples. As a validation step, most of these bacteria were also closely associated with colorectal cancer in previous studies with alternative approaches. In summary, our approach provides a new analytic technique for investigating the infiltrating bacterial community within tumor tissues. Our novel cloud-based bioinformatics and statistical pipelines to analyze the infiltrating bacteria in colorectal tumors using the unmapped reads of whole genome sequences can be freely accessed from GitHub at https://github.com/gutmicrobes/UMIB.git.}, }
@article {pmid30930863, year = {2019}, author = {Reid, G and Gadir, AA and Dhir, R}, title = {Probiotics: Reiterating What They Are and What They Are Not.}, journal = {Frontiers in microbiology}, volume = {10}, number = {}, pages = {424}, pmid = {30930863}, issn = {1664-302X}, abstract = {It has been over seventeen years since the scientific definition of probiotics was crafted, along with guidelines ensuring the appropriate use of the term. This definition is now used globally, yet on a consistent basis scientists, media and industry misrepresent probiotics or make generalized statements that illustrate a misunderstanding of their utility and limitations. The rate of discovery of novel organisms with potentially therapeutic benefit for both human and environmental health is progressing at an unprecedented rate. However, the term "probiotic" is often misapplied to describe any microbe with plausible therapeutic utility in the human host. It is argued that strict compliance to the scientific definition of the term "probiotic" and avoidance of generalizations to the whole field of probiotics based upon studies of one product, will help advance the development and validation of microbial therapies, and applications to improve human health.}, }
@article {pmid30925932, year = {2019}, author = {van der Veer, C and Hertzberger, RY and Bruisten, SM and Tytgat, HLP and Swanenburg, J and de Kat Angelino-Bart, A and Schuren, F and Molenaar, D and Reid, G and de Vries, H and Kort, R}, title = {Comparative genomics of human Lactobacillus crispatus isolates reveals genes for glycosylation and glycogen degradation: implications for in vivo dominance of the vaginal microbiota.}, journal = {Microbiome}, volume = {7}, number = {1}, pages = {49}, pmid = {30925932}, issn = {2049-2618}, mesh = {Bacterial Proteins/genetics ; Dysbiosis/*microbiology ; Female ; Genome, Bacterial ; Genomics/*methods ; Glycogen/*metabolism ; Glycosylation ; Glycosyltransferases/genetics ; Humans ; Lactobacillus crispatus/genetics/*isolation &amp; purification/metabolism ; Neisseria gonorrhoeae/growth &amp; development ; Phenotype ; Phylogeny ; Sequence Analysis, DNA ; Vagina/*microbiology ; }, abstract = {BACKGROUND: A vaginal microbiota dominated by lactobacilli (particularly Lactobacillus crispatus) is associated with vaginal health, whereas a vaginal microbiota not dominated by lactobacilli is considered dysbiotic. Here we investigated whether L. crispatus strains isolated from the vaginal tract of women with Lactobacillus-dominated vaginal microbiota (LVM) are pheno- or genotypically distinct from L. crispatus strains isolated from vaginal samples with dysbiotic vaginal microbiota (DVM).<br><br>RESULTS: We studied 33&#x2009;L. crispatus strains (n&#x2009;=&#x2009;16 from LVM; n&#x2009;=&#x2009;17 from DVM). Comparison of these two groups of strains showed that, although strain differences existed, both groups degraded various carbohydrates, produced similar amounts of organic acids, inhibited Neisseria gonorrhoeae growth, and did not produce biofilms. Comparative genomics analyses of 28 strains (n&#x2009;=&#x2009;12 LVM; n&#x2009;=&#x2009;16 DVM) revealed a novel, 3-fragmented glycosyltransferase gene that was more prevalent among strains isolated from DVM. Most L. crispatus strains showed growth on glycogen-supplemented growth media. Strains that showed less-efficient (n&#x2009;=&#x2009;6) or no (n&#x2009;=&#x2009;1) growth on glycogen all carried N-terminal deletions (respectively, 29 and 37 amino acid deletions) in a putative pullulanase type I protein.<br><br>DISCUSSION: L. crispatus strains isolated from LVM were not phenotypically distinct from L. crispatus strains isolated from DVM; however, the finding that the latter were more likely to carry a 3-fragmented glycosyltransferase gene may indicate a role for cell surface glycoconjugates, which may shape vaginal microbiota-host interactions. Furthermore, the observation that variation in the pullulanase type I gene is associated with growth on glycogen discourages previous claims that L. crispatus cannot directly utilize glycogen.}, }
@article {pmid30923584, year = {2018}, author = {Li, Z and Lee, K and Karagas, MR and Madan, JC and Hoen, AG and O'Malley, AJ and Li, H}, title = {Conditional Regression Based on a Multivariate Zero-Inflated Logistic-Normal Model for Microbiome Relative Abundance Data.}, journal = {Statistics in biosciences}, volume = {10}, number = {3}, pages = {587-608}, pmid = {30923584}, issn = {1867-1764}, support = {R01 GM123056/GM/NIGMS NIH HHS/United States ; UH3 OD023275/OD/NIH HHS/United States ; R01 GM123014/GM/NIGMS NIH HHS/United States ; R01 LM012723/LM/NLM NIH HHS/United States ; K01 LM011985/LM/NLM NIH HHS/United States ; P01 ES022832/ES/NIEHS NIH HHS/United States ; UG3 OD023275/OD/NIH HHS/United States ; R01 CA127334/CA/NCI NIH HHS/United States ; P20 GM104416/GM/NIGMS NIH HHS/United States ; }, abstract = {The human microbiome plays critical roles in human health and has been linked to many diseases. While advanced sequencing technologies can characterize the composition of the microbiome in unprecedented detail, it remains challenging to disentangle the complex interplay between human microbiome and disease risk factors due to the complicated nature of microbiome data. Excessive numbers e f zero values, high dimensionality, the hierarchical phylogenetic tree and compositional structure are compounded and consequently make existing methods inadequate to appropriately address these issues. We propose a multivariate two-part zero-inflated logistic normal (MZILN) model to analyze the association of disease risk factors with individual microbial taxa and overall microbial community composition. This approach can naturally handle excessive numbers e f zeros and the compositional data structure with the discrete part and the logistic-normal part e f the model. For parameter estimation, an estimating equations approach is employed that enables us to address the complex inter-taxa correlation structure induced by the hierarchical phylogenetic tree structure and the compositional data structure. This model is able to incorporate standard regularization approaches to deal with high dimensionality. Simulation shews that our model outperforms existing methods. Our approach is also compared to ethers using the analysis of real microbiome data.}, }
@article {pmid30920647, year = {2019}, author = {Hidalgo-Cantabrana, C and Gómez, J and Delgado, S and Requena-López, S and Queiro-Silva, R and Margolles, A and Coto, E and Sánchez, B and Coto-Segura, P}, title = {Gut microbiota dysbiosis in a cohort of patients with psoriasis.}, journal = {The British journal of dermatology}, volume = {181}, number = {6}, pages = {1287-1295}, doi = {10.1111/bjd.17931}, pmid = {30920647}, issn = {1365-2133}, support = {AGL2013-44039R//Spanish 'Programa Estatal de Investigaci&#xf3;n, Desarrollo e Innovaci&#xf3;n Orientada a los Retos de la Sociedad'/International ; PS-2016//Fundaci&#xf3;n Cient&#xed;fica Asociaci&#xf3;n Espa&#xf1;ola Contra el C&#xe1;ncer/International ; PI16/01792//'Fondo de Investigaciones Sanitarias' (FIS)/International ; }, mesh = {Adult ; Cohort Studies ; DNA, Bacterial/isolation &amp; purification ; Dysbiosis/*complications/diagnosis/immunology/microbiology ; Feces/microbiology ; Female ; Gastrointestinal Microbiome/genetics/*immunology ; Healthy Volunteers ; Humans ; Male ; Middle Aged ; Psoriasis/*immunology/microbiology ; RNA, Ribosomal, 16S/genetics ; }, abstract = {BACKGROUND: There is increasing evidence of the key role that the gut microbiota plays in inflammatory diseases.<br><br>OBJECTIVES: To identify differences in the faecal microbial composition of patients with psoriasis compared with healthy individuals in order to unravel the microbiota profiling in this autoimmune disease.<br><br>METHODS: 16S rRNA gene sequencing and bioinformatic analyses were performed with the total DNA extracted from the faecal microbiota of 19 patients with psoriasis and 20 healthy individuals from the same geographic location.<br><br>RESULTS: Gut microbiota composition of patients with psoriasis displayed a lower diversity and different relative abundance of certain bacterial taxa compared with healthy individuals.<br><br>CONCLUSIONS: The gut microbiota profile of patients with psoriasis displayed a clear dysbiosis that can be targeted for microbiome-based therapeutic approaches. What's already known about this topic? Psoriasis is a chronic inflammatory immune-mediated skin disease, the aetiology of which remains unclear. The human microbiota is a complex microbial community that inhabits our body and has been related with the maintenance of a healthy status. Several studies have focused on the skin microbiome and its connection with psoriasis although less attention has been focused on the potential role of the gut microbiota in psoriatic disease. What does this study add? This study unravels the gut microbiome dysbiosis present in a cohort of patients with psoriasis, compared with a healthy control group from the same geographical location. This study shows a lower bacterial diversity and different relative abundance of certain bacterial taxa in patients with psoriasis. We gain knowledge and insight into the microbiome alterations in psoriatic disease, opening new avenues for therapeutic approaches to reshape the human microbiome towards a healthy status.}, }
@article {pmid30919073, year = {2019}, author = {Ames, NJ and Barb, JJ and Ranucci, A and Kim, H and Mudra, SE and Cashion, AK and Townsley, DM and Childs, R and Paster, BJ and Faller, LL and Wallen, GR}, title = {The oral microbiome of patients undergoing treatment for severe aplastic anemia: a pilot study.}, journal = {Annals of hematology}, volume = {98}, number = {6}, pages = {1351-1365}, doi = {10.1007/s00277-019-03599-w}, pmid = {30919073}, issn = {1432-0584}, mesh = {Adult ; Aged ; Anemia, Aplastic/drug therapy/*microbiology/therapy ; Anti-Bacterial Agents/pharmacology ; Antilymphocyte Serum/therapeutic use ; Benzoates/pharmacology/therapeutic use ; Biodiversity ; Cyclosporine/therapeutic use ; DNA, Bacterial/analysis ; Dental Health Surveys ; Female ; Graft vs Host Disease/etiology/microbiology ; Hematopoietic Stem Cell Transplantation ; Humans ; Hydrazines/pharmacology/therapeutic use ; Immunocompromised Host ; Immunosuppressive Agents/therapeutic use ; Male ; *Microbiota/drug effects ; Middle Aged ; Mouth/*microbiology ; Pilot Projects ; Pyrazoles/pharmacology/therapeutic use ; Ribotyping ; Sequence Analysis, DNA ; Smoking/epidemiology ; T-Lymphocytes/immunology ; Tongue/microbiology ; Young Adult ; }, abstract = {The microbiome, an intriguing component of the human body, composed of trillions of microorganisms, has prompted scientific exploration to identify and understand its function and role in health and disease. As associations between microbiome composition, disease, and symptoms accumulate, the future of medicine hinges upon a comprehensive knowledge of these microorganisms for patient care. The oral microbiome may provide valuable and efficient insight for predicting future changes in disease status, infection, or treatment course. The main aim of this pilot study was to characterize the oral microbiome in patients with severe aplastic anemia (SAA) during their therapeutic course. SAA is a hematologic disease characterized by bone marrow failure which if untreated is fatal. Treatment includes either hematopoietic stem cell transplantation (HSCT) or immunosuppressive therapy (IST). In this study, we examined the oral microbiome composition of 24 patients admitted to the National Institutes of Health (NIH) Clinical Center for experimental SAA treatment. Tongue brushings were collected to assess the effects of treatment on the oral microbiome. Twenty patients received standard IST (equine antithymocyte globulin and cyclosporine) plus eltrombopag. Four patients underwent HSCT. Oral specimens were obtained at three time points during treatment and clinical follow-up. Using a novel approach to 16S rRNA gene sequence analysis encompassing seven hypervariable regions, results demonstrated a predictable decrease in microbial diversity over time among the transplant patients. Linear discriminant analysis or LefSe reported a total of 14 statistically significant taxa (p < 0.05) across time points in the HSCT patients. One-way plots of relative abundance for two bacterial species (Haemophilus parainfluenzae and Rothia mucilaginosa) in the HSCT group, show the differences in abundance between time points. Only one bacterial species (Prevotella histicola) was noted in the IST group with a p value of 0.065. The patients receiving immunosuppressive therapy did not exhibit a clear change in diversity over time; however, patient-specific changes were noted. In addition, we compared our findings to tongue dorsum samples from healthy participants in the Human Microbiome Project (HMP) database and found among HSCT patients, approximately 35% of bacterial identifiers (N = 229) were unique to this study population and were not present in tongue dorsum specimens obtained from the HMP. Among IST-treated patients, 45% (N = 351) were unique to these patients and not identified by the HMP. Although antibiotic use may have likely influenced bacterial composition and diversity, some literature suggests a decreased impact of antimicrobials on the oral microbiome as compared to their effect on the gut microbiome. Future studies with larger sample sizes that focus on the oral microbiome and the effects of antibiotics in an immunosuppressed patient population may help establish these potential associations.}, }
@article {pmid30918980, year = {2019}, author = {Shannon, MB and Limeira, R and Johansen, D and Gao, X and Lin, H and Dong, Q and Wolfe, AJ and Mueller, ER}, title = {Bladder urinary oxygen tension is correlated with urinary microbiota composition.}, journal = {International urogynecology journal}, volume = {30}, number = {8}, pages = {1261-1267}, pmid = {30918980}, issn = {1433-3023}, mesh = {Adult ; Aged ; Aged, 80 and over ; Correlation of Data ; Female ; Humans ; *Microbiota ; Middle Aged ; Oxygen/*urine ; Urinary Bladder/*metabolism/*microbiology ; Young Adult ; }, abstract = {INTRODUCTION AND HYPOTHESIS: Presence of microbial communities (microbiota) in an organ system depends on environmental factors, such as oxygen availability. We describe a novel technique to measure bladder urine oxygen tension (BUOT) in ambulatory women and use that technique to compare BUOT values to female urinary microbiota and participant urinary signs and symptoms.<br><br>METHODS: Ambulatory female urogynecology patients presenting for clinical care who were willing to undergo transurethral catheterization underwent BUOT determination with a non-invasive flow-through oxygen sensor. To detect urinary microbiota in the bladder, 16S rRNA gene sequencing was performed on catheterized urine. Multivariate statistical analyses were performed to examine potential correlations among BUOT, urinary microbiota compositions and clinical variables.<br><br>RESULTS: Significant variation in BUOT existed between individuals (range: 0.47-51.5&#xa0;mmHg; median: 23.1&#x2009;&#xb1;&#x2009;13.5). Microbiota compositions were associated with BUOT (p&#x2009;=&#x2009;0.03). BUOT was significantly lower in urines that were nitrite negative on dipstick analysis (p&#x2009;=&#x2009;0.0001) and in participants who answered yes to having urinary leakage on the validated Urinary Distress Inventory (p&#x2009;=&#x2009;0.01).<br><br>CONCLUSIONS: BUOTs can be measured in ambulatory women. For urogynecology patients, a wide range of values exist. BUOT may be associated with the presence of urinary microbiota and resultant signs and symptoms.}, }
@article {pmid30917589, year = {2019}, author = {George, A}, title = {Antimicrobial Resistance (AMR) in the Food Chain: Trade, One Health and Codex.}, journal = {Tropical medicine and infectious disease}, volume = {4}, number = {1}, pages = {}, pmid = {30917589}, issn = {2414-6366}, abstract = {Strategies that take on a One Health approach to addressing antimicrobial resistance (AMR) focused on reducing human use of antimicrobials, but policy-makers now have to grapple with a different set of political, economic, and highly sensitive trade interests less amenable to government direction, to tackle AMR in the food chain. Understanding the importance and influence of the intergovernmental Codex negotiations underway on AMR in the Food Chain is very weak but essential for AMR public policy experts. National and global food producing industries are already under pressure as consumers learn about the use of antimicrobials in food production and more so when the full impact of AMR microorganisms in the food chain and on the human microbiome is better understood. Governments will be expected to respond. Trade-related negotiations on access and use made of antimicrobials is political: the relevance of AMR 'evidence' is already contested and not all food producers or users of antimicrobials in the food chain are prepared to, or capable of, moving at the same pace. In trade negotiations governments defend their interpretation of national interest. Given AMR in the global food chain threatens national interest, both AMR One Health and zoonotic disease experts should understand and participate in all trade-related AMR negotiations to protect One Health priorities. To help facilitate this an overview and analysis of Codex negotiations is provided.}, }
@article {pmid30911128, year = {2019}, author = {Brito, IL and Gurry, T and Zhao, S and Huang, K and Young, SK and Shea, TP and Naisilisili, W and Jenkins, AP and Jupiter, SD and Gevers, D and Alm, EJ}, title = {Transmission of human-associated microbiota along family and social networks.}, journal = {Nature microbiology}, volume = {4}, number = {6}, pages = {964-971}, pmid = {30911128}, issn = {2058-5276}, support = {R01 DK093595/DK/NIDDK NIH HHS/United States ; U54 HG003067/HG/NHGRI NIH HHS/United States ; }, mesh = {Bacteria/genetics ; *Family ; Female ; Fiji ; Gastrointestinal Microbiome/genetics ; Genomics ; Genotype ; Host Specificity ; Humans ; Interspersed Repetitive Sequences ; Male ; *Microbiota/genetics ; Polymorphism, Single Nucleotide ; *Social Networking ; }, abstract = {The human microbiome, described as an accessory organ because of the crucial functions it provides, is composed of species that are uniquely found in humans[1,2]. Yet, surprisingly little is known about the impact of routine interpersonal contacts in shaping microbiome composition. In a relatively 'closed' cohort of 287 people from the Fiji Islands, where common barriers to bacterial transmission are absent, we examine putative bacterial transmission in individuals' gut and oral microbiomes using strain-level data from both core single-nucleotide polymorphisms and flexible genomic regions. We find a weak signal of transmission, defined by the inferred sharing of genotypes, across many organisms that, in aggregate, reveals strong transmission patterns, most notably within households and between spouses. We were unable to determine the directionality of transmission nor whether it was direct. We further find that women harbour strains more closely related to those harboured by their familial and social contacts than men, and that transmission patterns of oral-associated and gut-associated microbiota need not be the same. Using strain-level data alone, we are able to confidently predict a subset of spouses, highlighting the role of shared susceptibilities, behaviours or social interactions that distinguish specific links in the social network.}, }
@article {pmid30910274, year = {2019}, author = {Leynaert, B and Le Moual, N and Neukirch, C and Siroux, V and Varraso, R}, title = {[Environmental risk factors for asthma developement].}, journal = {Presse medicale (Paris, France : 1983)}, volume = {48}, number = {3 Pt 1}, pages = {262-273}, doi = {10.1016/j.lpm.2019.02.022}, pmid = {30910274}, issn = {2213-0276}, mesh = {Air Pollution, Indoor/adverse effects ; Allergens/adverse effects ; Animals ; Asthma/*etiology/microbiology ; Environmental Exposure/*adverse effects ; Humans ; Risk Factors ; }, abstract = {The prevalence of asthma has increased rapidly since the early 1970s, and only changes in exposure to environmental factors; which go together with changes in lifestyle, are likely to explain such a rapid increase. Exposure to allergens is a risk factor for allergic sensitization, and allergic sensitization is a risk factor for allergic asthma. However, apart from indoor mold exposure as a risk factor for childhood asthma, there is insufficient evidence to conclude that the associations between allergen exposure and asthma development are causal. A new challenge for research is to analyze the huge amount of data derived from the metagenomic characterization of the environmental and human microbiome, to understand the role of interactions between viruses, bacteria and allergens in the development of asthma. It is recognized that prenatal and postnatal exposure to air pollution and maternal smoking increase the risk of developing asthma in children. In adults, the data are scarce and the results remain controversial as regards these exposures and asthma incidence. Further research is needed to appraise the effect of exposure to phenols, phthalates and perfluorinated compounds, which are widespread in the environment and may be associated with asthma, especially in children. Frequent use of chemicals for home cleaning especially in the form of sprays - which is a common practice at the population level - is a risk factor for the development of adult asthma. The domestic use of cleaning products might also be a risk factor for asthma in children exposed at home. The chemicals involved in these relationships are still to be identified. Occupational asthma is a major phenotype of adult asthma. A significant part of these asthma cases might relate to occupational exposure to cleaning products. While there is evidence of associations between diet during pregnancy or during childhood and the risk of developing asthma in children, the data in adults are insufficient. Beyond genetic factors, body composition is influenced by dietary choices and physical activity. Further research is needed to clarify the complex interplay between these nutritional factors and asthma development. The new challenge for research is to decipher the role of all the environmental factors to which the individual is exposed since conception ("exposome") in the development of asthma, using a holistic approach.}, }
@article {pmid30908947, year = {2019}, author = {Ahern, GJ and Hennessy, AA and Ryan, CA and Ross, RP and Stanton, C}, title = {Advances in Infant Formula Science.}, journal = {Annual review of food science and technology}, volume = {10}, number = {}, pages = {75-102}, doi = {10.1146/annurev-food-081318-104308}, pmid = {30908947}, issn = {1941-1421}, mesh = {Animals ; Cattle ; Humans ; Infant ; *Infant Formula ; Infant Nutritional Physiological Phenomena ; Microbiota ; Milk ; }, abstract = {Human milk contains a plethora of nutrients and bioactive components to help nourish the developing neonate and is considered the "gold standard" for early life nutrition-as befits the only food "designed" by evolution to feed human infants. Over the past decade, there is considerable evidence that highlights the "intelligence" contained in milk components that contribute to infant health beyond basic nutrition-in areas such as programming the developing microbiome and immune system and protecting against infection. Such discoveries have led to new opportunities for infant milk formula (IMF) manufacturers to refine nutritional content in order to simulate the functionality of breast milk. These include the addition of specialized protein fractions as well as fatty acid and complex carbohydrate components-all of which have mechanistic supporting evidence in terms of improving the health and nutrition of the infant. Moreover, IMF is the single most important dietary intervention whereby the human microbiome can be influenced at a crucial early stage of development. In this respect, it is expected that the complexity of IMF will continue to increase as we get a greater understanding of how it can modulate microbiota development (including the development of probiotics, prebiotics, and synbiotics) and influence long-term health. This review provides a scientific evaluation of key features of importance to infant nutrition, including differences in milk composition and emerging "humanized" ingredients.}, }
@article {pmid30899033, year = {2019}, author = {Reddel, S and Del Chierico, F and Quagliariello, A and Giancristoforo, S and Vernocchi, P and Russo, A and Fiocchi, A and Rossi, P and Putignani, L and El Hachem, M}, title = {Gut microbiota profile in children affected by atopic dermatitis and evaluation of intestinal persistence of a probiotic mixture.}, journal = {Scientific reports}, volume = {9}, number = {1}, pages = {4996}, pmid = {30899033}, issn = {2045-2322}, mesh = {Bacteroides/genetics ; Child ; Child, Preschool ; Dermatitis, Atopic/*genetics/microbiology/pathology ; Dysbiosis/*genetics/microbiology/pathology ; Faecalibacterium/genetics ; Feces/microbiology ; Female ; Gastrointestinal Microbiome/*genetics ; Humans ; Infant ; Infant, Newborn ; Intestines/microbiology ; Male ; *Metagenomics ; Probiotics/metabolism ; RNA, Ribosomal, 16S/genetics ; }, abstract = {Atopic dermatitis (AD) has been hypothesised to be associated with gut microbiota (GM) composition. We performed a comparative study of the GM profile of 19 AD children and 18 healthy individuals aimed at identifying bacterial biomarkers associated with the disease. The effect of probiotic intake (Bifidobacterium breve plus Lactobacillus salivarius) on the modulation of GM and the probiotic persistence in the GM were also evaluated. Faecal samples were analysed by real-time PCR and 16S rRNA targeted metagenomics. Although the probiotics, chosen for this study, did not shape the entire GM profile, we observed the ability of these species to pass through the gastrointestinal tract and to persist (only B. breve) in the GM. Moreover, the GM of patients compared to CTRLs showed a dysbiotic status characterised by an increase of Faecalibacterium, Oscillospira, Bacteroides, Parabacteroides and Sutterella and a reduction of short-chain fatty acid (SCFA)-producing bacteria (i.e., Bifidobacterium, Blautia, Coprococcus, Eubacterium and Propionibacterium). Taken togheter these results show an alteration in AD microbiota composition with the depletion or absence of some species, opening the way to future probiotic intervention studies.}, }
@article {pmid30895406, year = {2019}, author = {Nguyen, VD and Nguyen, TT and Pham, TT and Packianather, M and Le, CH}, title = {Molecular screening and genetic diversity analysis of anticancer Azurin-encoding and Azurin-like genes in human gut microbiome deduced through cultivation-dependent and cultivation-independent studies.}, journal = {International microbiology : the official journal of the Spanish Society for Microbiology}, volume = {22}, number = {4}, pages = {437-449}, doi = {10.1007/s10123-019-00070-8}, pmid = {30895406}, issn = {1618-1905}, support = {106-YS.04-2014.40//National Foundation for Science and Technology Development/ ; }, mesh = {Adolescent ; Adult ; Azurin/*genetics/metabolism ; Child ; Culture Media/metabolism ; Feces/microbiology ; Female ; *Gastrointestinal Microbiome ; Genetic Variation ; Humans ; Male ; Phylogeny ; Pseudomonas aeruginosa/*genetics/growth &amp; development/*isolation &amp; purification/metabolism ; Young Adult ; }, abstract = {Azurin, a bacteriocin produced by a human gut bacterium Pseudomonas aeruginosa, can reveal selectively cytotoxic and induce apoptosis in cancer cells. After overcoming two phase I trials, a functional region of Azurin called p28 has been approved as a drug for the treatment of brain tumor glioma by FDA. The present study aims to improve a screening procedure and assess genetic diversity of Azurin genes in P. aeruginosa and Azurin-like genes in the gut microbiome of a specific population in Vietnam and global populations. Firstly, both cultivation-dependent and cultivation-independent techniques based on genomic and metagenomic DNAs extracted from fecal samples of the healthy specific population were performed and optimized to detect Azurin genes. Secondly, the Azurin gene sequences were analyzed and compared with global populations by using bioinformatics tools. Finally, the screening procedure improved from the first step was applied for screening Azurin-like genes, followed by the protein synthesis and NCI in vitro screening for anticancer activity. As a result, this study has successfully optimized the annealing temperatures to amplify DNAs for screening Azurin genes and applying to Azurin-like genes from human gut microbiota. The novelty of this study is the first of its kind to classify Azurin genes into five different genotypes at a global scale and confirm the potential anticancer activity of three Azurin-like synthetic proteins (Cnazu1, Dlazu11, and Ruazu12). The results contribute to the procedure development applied for screening anticancer proteins from human microbiome and a comprehensive understanding of their therapeutic response at a genetic level.}, }
@article {pmid30894847, year = {2019}, author = {Brown, EEF and Cooper, A and Carrillo, C and Blais, B}, title = {Selection of Multidrug-Resistant Bacteria in Medicated Animal Feeds.}, journal = {Frontiers in microbiology}, volume = {10}, number = {}, pages = {456}, pmid = {30894847}, issn = {1664-302X}, abstract = {Exposure to antimicrobial resistant (AMR) bacteria is a major public health issue which may, in part, have roots in food production practices that are conducive to the selection of AMR bacteria ultimately impacting the human microbiome through food consumption. Of particular concern is the prophylactic use of antibiotics in animal husbandry, such as the medication of feeds with sulfonamides and other antibiotics not considered clinically relevant, but which may nonetheless co-select for multi-drug resistant (MDR) bacteria harboring resistance to medically important antibiotics. Using a MDR Klebsiella pneumoniae strain exhibiting resistance to sulfonamides and beta-lactams (including carbapenem) as a model, we examined the ability of non-medicated and commercially medicated (sulfonamide) animal feeds to select for the model strain when inoculated at low levels by measuring its recovery along with key AMR markers, sul1(sulfonamide) and blaKPC-3 (meropenem), under different incubation conditions. When non-medicated feeds were supplemented with defined amounts of sulfadiazine the model strain was significantly enriched after incubation in Mueller Hinton Broth at 37°C overnight, or in same at room temperature for a week, with consistent detection of both the sul1 and blaKPC-3 markers as determined by polymerase chain reaction (PCR) techniques to screen colony isolates recovered on plating media. Significant recoveries of the inoculated strain and the sul1 and blaKPC-3 markers were observed with one of three commercially medicated (sulfamethazine) feeds tested under various incubation conditions. These results demonstrate that under certain conditions the prophylactic use of so-called non-priority antibiotics in feeds can potentially lead to co-selection of environmental AMR bacteria with resistance to medically important antibiotics, which may have far-reaching implications for human health.}, }
@article {pmid30894688, year = {2019}, author = {Ma, ZS and Li, L and Gotelli, NJ}, title = {Diversity-disease relationships and shared species analyses for human microbiome-associated diseases.}, journal = {The ISME journal}, volume = {13}, number = {8}, pages = {1911-1919}, pmid = {30894688}, issn = {1751-7370}, mesh = {Bacteria/classification/genetics/*isolation &amp; purification ; Biodiversity ; Disease ; Health ; Humans ; *Microbiota ; }, abstract = {Diversity indices have been routinely computed in the study of human microbiome-associated diseases (MADs). However, it is still unclear whether there is a consistent diversity-disease relationship (DDR) for the human MADs, and whether there are consistent differences in the taxonomic composition of microbiomes sampled from healthy versus diseased individuals. Here we reanalyzed raw data and used a meta-analysis to compare the microbiome diversity and composition of healthy versus diseased individuals in 41 comparisons extracted from 27 previously published studies of human MADs. In the DDR analysis, the average effect size across studies did not differ from zero for a comparison of healthy versus diseased individuals. In 30 of 41 comparisons (73%) there was no significant difference in microbiome diversity of healthy versus diseased individuals, or of different disease classes. For the species composition analysis (shared species analysis), the effect sizes were significantly different from zero. In 33 of 41 comparisons (80%), there were fewer OTUs (operational taxonomic units) shared between healthy and diseased individuals than expected by chance, but with 49% (20 of 41 comparisons) statistically significant. These results imply that the taxonomic composition of disease-associated microbiomes is often distinct from that of healthy individuals. Because species composition changes with disease state, some microbiome OTUs may serve as potential diagnostic indicators of disease. However, the overall species diversity of human microbiomes is not a reliable indicator of disease.}, }
@article {pmid30890301, year = {2019}, author = {Chen, QL and Cui, HL and Su, JQ and Penuelas, J and Zhu, YG}, title = {Antibiotic Resistomes in Plant Microbiomes.}, journal = {Trends in plant science}, volume = {24}, number = {6}, pages = {530-541}, doi = {10.1016/j.tplants.2019.02.010}, pmid = {30890301}, issn = {1878-4372}, support = {/ERC_/European Research Council/International ; }, mesh = {*Anti-Bacterial Agents ; Bacteria ; Drug Resistance, Microbial ; Humans ; *Microbiota ; Plants ; }, abstract = {Microorganisms associated with plants may alter the traits of the human microbiome important for human health, but this alteration has largely been overlooked. The plant microbiome is an interface between plants and the environment, and provides many ecosystem functions such as improving nutrient uptake and protecting against biotic and abiotic stress. The plant microbiome also represents a major pathway by which humans are exposed to microbes and genes consumed with food, such as pathogenic bacteria, antibiotic-resistant bacteria, and antibiotic-resistance genes. In this review we highlight the main findings on the composition and function of the plant microbiome, and underline the potential of plant microbiomes in the dissemination of antibiotic resistance via food consumption or direct contact.}, }
@article {pmid30890187, year = {2019}, author = {Tovaglieri, A and Sontheimer-Phelps, A and Geirnaert, A and Prantil-Baun, R and Camacho, DM and Chou, DB and Jalili-Firoozinezhad, S and de Wouters, T and Kasendra, M and Super, M and Cartwright, MJ and Richmond, CA and Breault, DT and Lacroix, C and Ingber, DE}, title = {Species-specific enhancement of enterohemorrhagic E. coli pathogenesis mediated by microbiome metabolites.}, journal = {Microbiome}, volume = {7}, number = {1}, pages = {43}, pmid = {30890187}, issn = {2049-2618}, support = {K08 DK106562/DK/NIDDK NIH HHS/United States ; P30 DK034854/DK/NIDDK NIH HHS/United States ; R01 DK084056/DK/NIDDK NIH HHS/United States ; T32 CA009216/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Bacteria/*metabolism ; Benzoates/pharmacology ; Caproates/pharmacology ; Cells, Cultured ; Enterohemorrhagic Escherichia coli/metabolism/*pathogenicity ; Escherichia coli Infections/microbiology/*pathology ; Female ; Gastrointestinal Microbiome ; Heptanoic Acids/pharmacology ; Humans ; Intestines/*cytology/microbiology ; Male ; Mice ; Microchip Analytical Procedures ; Organ Culture Techniques/*methods ; Species Specificity ; }, abstract = {BACKGROUND: Species-specific differences in tolerance to infection are exemplified by the high susceptibility of humans to enterohemorrhagic Escherichia coli (EHEC) infection, whereas mice are relatively resistant to this pathogen. This intrinsic species-specific difference in EHEC infection limits the translation of murine research to human. Furthermore, studying the mechanisms underlying this differential susceptibility is a difficult problem due to complex in vivo interactions between the host, pathogen, and disparate commensal microbial communities.<br><br>RESULTS: We utilize organ-on-a-chip (Organ Chip) microfluidic culture technology to model damage of the human colonic epithelium induced by EHEC infection, and show that epithelial injury is greater when exposed to metabolites derived from the human gut microbiome compared to mouse. Using a multi-omics approach, we discovered four human microbiome metabolites-4-methyl benzoic acid, 3,4-dimethylbenzoic acid, hexanoic acid, and heptanoic acid-that are sufficient to mediate this effect. The active human microbiome metabolites preferentially induce expression of flagellin, a bacterial protein associated with motility of EHEC and increased epithelial injury. Thus, the decreased tolerance to infection observed in humans versus other species may be due in part to the presence of compounds produced by the human intestinal microbiome that actively promote bacterial pathogenicity.<br><br>CONCLUSION: Organ-on-chip technology allowed the identification of specific human microbiome metabolites modulating EHEC pathogenesis. These identified metabolites are sufficient to increase susceptibility to EHEC in our human Colon Chip model and they contribute to species-specific tolerance. This work suggests that higher concentrations of these metabolites could be the reason for higher susceptibility to EHEC infection in certain human populations, such as children. Furthermore, this research lays the foundation for therapeutic-modulation of microbe products in order to prevent and treat human bacterial infection.}, }
@article {pmid30885720, year = {2019}, author = {LaPierre, N and Ju, CJ and Zhou, G and Wang, W}, title = {MetaPheno: A critical evaluation of deep learning and machine learning in metagenome-based disease prediction.}, journal = {Methods (San Diego, Calif.)}, volume = {166}, number = {}, pages = {74-82}, pmid = {30885720}, issn = {1095-9130}, support = {R01 GM115833/GM/NIGMS NIH HHS/United States ; T32 EB016640/EB/NIBIB NIH HHS/United States ; }, mesh = {Algorithms ; *Deep Learning ; Diabetes Mellitus, Type 2/*genetics/microbiology ; Humans ; Machine Learning/statistics &amp; numerical data ; Metagenome/*genetics ; Metagenomics/methods ; Microbiota/genetics ; Obesity/*genetics/microbiology ; }, abstract = {The human microbiome plays a number of critical roles, impacting almost every aspect of human health and well-being. Conditions in the microbiome have been linked to a number of significant diseases. Additionally, revolutions in sequencing technology have led to a rapid increase in publicly-available sequencing data. Consequently, there have been growing efforts to predict disease status from metagenomic sequencing data, with a proliferation of new approaches in the last few years. Some of these efforts have explored utilizing a powerful form of machine learning called deep learning, which has been applied successfully in several biological domains. Here, we review some of these methods and the algorithms that they are based on, with a particular focus on deep learning methods. We also perform a deeper analysis of Type 2 Diabetes and obesity datasets that have eluded improved results, using a variety of machine learning and feature extraction methods. We conclude by offering perspectives on study design considerations that may impact results and future directions the field can take to improve results and offer more valuable conclusions. The scripts and extracted features for the analyses conducted in this paper are available via GitHub:https://github.com/nlapier2/metapheno.}, }
@article {pmid30880022, year = {2019}, author = {Cohen, LJ and Cho, JH and Gevers, D and Chu, H}, title = {Genetic Factors and the Intestinal Microbiome Guide Development of Microbe-Based Therapies for Inflammatory Bowel Diseases.}, journal = {Gastroenterology}, volume = {156}, number = {8}, pages = {2174-2189}, pmid = {30880022}, issn = {1528-0012}, support = {U24 DK062429/DK/NIDDK NIH HHS/United States ; U01 DK062429/DK/NIDDK NIH HHS/United States ; U01 DK062422/DK/NIDDK NIH HHS/United States ; K08 DK109287/DK/NIDDK NIH HHS/United States ; R01 DK092235/DK/NIDDK NIH HHS/United States ; R00 DK110534/DK/NIDDK NIH HHS/United States ; R01 DK106593/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Drugs, Investigational/*administration &amp; dosage/pharmacology ; Gastrointestinal Microbiome/*genetics/*immunology ; Genome, Human ; Humans ; Immunotherapy/*methods ; Inflammatory Bowel Diseases/microbiology/pathology/*therapy ; Mice ; Models, Animal ; *Practice Guidelines as Topic ; Prognosis ; Treatment Outcome ; }, abstract = {The intestinal microbiota is a dynamic community of bacteria, fungi, and viruses that mediates mucosal homeostasis and physiology. Imbalances in the microbiome and aberrant immune responses to gut bacteria can disrupt homeostasis and are associated with inflammatory bowel diseases (IBDs) in humans and colitis in mice. We review genetic variants associated with IBD and their effects on the intestinal microbiome, the immune response, and disease pathogenesis. The intestinal microbiome, which includes microbial antigens, adjuvants, and metabolic products, affects the development and function of the intestinal mucosa, influencing inflammatory responses in the gut. Therefore, strategies to manipulate the microbiome might be used in treatment of IBD. We review microbe-based therapies for IBD and the potential to engineer patients' intestinal microbiota. We discuss how studies of patients with IBD and mouse models have advanced our understanding of the interactions between genetic factors and the gut microbiome, and challenges to the development of microbe-based therapies for IBD.}, }
@article {pmid30877283, year = {2019}, author = {Shaw, LP and Bassam, H and Barnes, CP and Walker, AS and Klein, N and Balloux, F}, title = {Modelling microbiome recovery after antibiotics using a stability landscape framework.}, journal = {The ISME journal}, volume = {13}, number = {7}, pages = {1845-1856}, pmid = {30877283}, issn = {1751-7370}, support = {//Wellcome Trust/United Kingdom ; 209409//Wellcome Trust/United Kingdom ; 097319/Z/11/Z/WT_/Wellcome Trust/United Kingdom ; }, mesh = {Anti-Bacterial Agents/*pharmacology ; Bayes Theorem ; Dysbiosis/*microbiology ; Gastrointestinal Microbiome/drug effects/physiology ; Humans ; Microbiota/*drug effects/physiology ; *Models, Theoretical ; }, abstract = {Treatment with antibiotics is one of the most extreme perturbations to the human microbiome. Even standard courses of antibiotics dramatically reduce the microbiome's diversity and can cause transitions to dysbiotic states. Conceptually, this is often described as a 'stability landscape': the microbiome sits in a landscape with multiple stable equilibria, and sufficiently strong perturbations can shift the microbiome from its normal equilibrium to another state. However, this picture is only qualitative and has not been incorporated in previous mathematical models of the effects of antibiotics. Here, we outline a simple quantitative model based on the stability landscape concept and demonstrate its success on real data. Our analytical impulse-response model has minimal assumptions with three parameters. We fit this model in a Bayesian framework to data from a previous study of the year-long effects of short courses of four common antibiotics on the gut and oral microbiomes, allowing us to compare parameters between antibiotics and microbiomes, and further validate our model using data from another study looking at the impact of a combination of last-resort antibiotics on the gut microbiome. Using Bayesian model selection we find support for a long-term transition to an alternative microbiome state after courses of certain antibiotics in both the gut and oral microbiomes. Quantitative stability landscape frameworks are an exciting avenue for future microbiome modelling.}, }
@article {pmid30876799, year = {2019}, author = {Douillard, FP and de Vos, WM}, title = {Biotechnology of health-promoting bacteria.}, journal = {Biotechnology advances}, volume = {37}, number = {6}, pages = {107369}, doi = {10.1016/j.biotechadv.2019.03.008}, pmid = {30876799}, issn = {1873-1899}, mesh = {Bifidobacterium ; *Biotechnology ; *Gastrointestinal Microbiome ; Humans ; *Probiotics ; }, abstract = {Over the last decade, there has been an increasing scientific and public interest in bacteria that may positively contribute to human gut health and well-being. This interest is reflected by the ever-increasing number of developed functional food products containing health-promoting bacteria and reaching the market place as well as by the growing revenue and profits of notably bacterial supplements worldwide. Traditionally, the origin of probiotic-marketed bacteria was limited to a rather small number of bacterial species that mostly belong to lactic acid bacteria and bifidobacteria. Intensifying research efforts on the human gut microbiome offered novel insights into the role of human gut microbiota in health and disease, while also providing a deep and increasingly comprehensive understanding of the bacterial communities present in this complex ecosystem and their interactions with the gut-liver-brain axis. This resulted in rational and systematic approaches to select novel health-promoting bacteria or to engineer existing bacteria with enhanced probiotic properties. In parallel, the field of gut microbiomics developed into a fertile framework for the identification, isolation and characterization of a phylogenetically diverse array of health-promoting bacterial species, also called next-generation therapeutic bacteria. The present review will address these developments with specific attention for the selection and improvement of a selected number of health-promoting bacterial species and strains that are extensively studied or hold promise for future food or pharma product development.}, }
@article {pmid30871856, year = {2019}, author = {Minot, SS}, title = {De novo Assembly Vastly Expands the Known Microbial Universe.}, journal = {Trends in microbiology}, volume = {27}, number = {5}, pages = {385-386}, doi = {10.1016/j.tim.2019.02.007}, pmid = {30871856}, issn = {1878-4380}, mesh = {Geography ; Humans ; Life Style ; *Metagenome ; *Microbiota ; }, abstract = {The study of the human microbiome relies heavily on the genomes of bacterial isolates that can be grown in culture. A recent study (Pasolli et al. Cell 2019;176:649-662) of stool microbiome samples generated over 150 000 microbial genomes without any culture, vastly expanding our knowledge of the biases in existing reference databases.}, }
@article {pmid30871469, year = {2019}, author = {Perz, AI and Giles, CB and Brown, CA and Porter, H and Roopnarinesingh, X and Wren, JD}, title = {MNEMONIC: MetageNomic Experiment Mining to create an OTU Network of Inhabitant Correlations.}, journal = {BMC bioinformatics}, volume = {20}, number = {Suppl 2}, pages = {96}, pmid = {30871469}, issn = {1471-2105}, support = {P20 GM103636/GM/NIGMS NIH HHS/United States ; P30 AG050911/AG/NIA NIH HHS/United States ; T32 AG052363/AG/NIA NIH HHS/United States ; U54 GM104938/GM/NIGMS NIH HHS/United States ; }, mesh = {Humans ; Metagenomics/*methods ; Microbiota/*genetics ; }, abstract = {BACKGROUND: The number of publicly available metagenomic experiments in various environments has been rapidly growing, empowering the potential to identify similar shifts in species abundance between different experiments. This could be a potentially powerful way to interpret new experiments, by identifying common themes and causes behind changes in species abundance.<br><br>RESULTS: We propose a novel framework for comparing microbial shifts between conditions. Using data from one of the largest human metagenome projects to date, the American Gut Project (AGP), we obtain differential abundance vectors for microbes using experimental condition information provided with the AGP metadata, such as patient age, dietary habits, or health status. We show it can be used to identify similar and opposing shifts in microbial species, and infer putative interactions between microbes. Our results show that groups of shifts with similar effects on microbiome can be identified and that similar dietary interventions display similar microbial abundance shifts.<br><br>CONCLUSIONS: Without comparison to prior data, it is difficult for experimentalists to know if their observed changes in species abundance have been observed by others, both in their conditions and in others they would never consider comparable. Yet, this can be a very important contextual factor in interpreting the significance of a shift. We've proposed and tested an algorithmic solution to this problem, which also allows for comparing the metagenomic signature shifts between conditions in the existing body of data.}, }
@article {pmid30870464, year = {2019}, author = {Burcham, ZM and Schmidt, CJ and Pechal, JL and Brooks, CP and Rosch, JW and Benbow, ME and Jordan, HR}, title = {Detection of critical antibiotic resistance genes through routine microbiome surveillance.}, journal = {PloS one}, volume = {14}, number = {3}, pages = {e0213280}, pmid = {30870464}, issn = {1932-6203}, mesh = {Anti-Bacterial Agents/*pharmacology ; Bacteria/drug effects/*genetics ; Bacterial Infections/*diagnosis/epidemiology/genetics/microbiology ; Cadaver ; Drug Resistance, Microbial/*genetics ; *Genes, Bacterial ; Humans ; *Metagenome ; Microbiota ; *Population Surveillance ; United States/epidemiology ; }, abstract = {Population-based public health data on antibiotic resistance gene carriage is poorly surveyed. Research of the human microbiome as an antibiotic resistance reservoir has primarily focused on gut associated microbial communities, but data have shown more widespread microbial colonization across organs than originally believed, with organs previously considered as sterile being colonized. Our study demonstrates the utility of postmortem microbiome sampling during routine autopsy as a method to survey antibiotic resistance carriage in a general population. Postmortem microbial sampling detected pathogens of public health concern including genes for multidrug efflux pumps, carbapenem, methicillin, vancomycin, and polymixin resistances. Results suggest that postmortem assessments of host-associated microbial communities are useful in acquiring community specific data while reducing selective-participant biases.}, }
@article {pmid30867232, year = {2019}, author = {Elzinga, J and van der Oost, J and de Vos, WM and Smidt, H}, title = {The Use of Defined Microbial Communities To Model Host-Microbe Interactions in the Human Gut.}, journal = {Microbiology and molecular biology reviews : MMBR}, volume = {83}, number = {2}, pages = {}, pmid = {30867232}, issn = {1098-5557}, mesh = {Animals ; Bacteria/classification ; Cell Culture Techniques ; *Gastrointestinal Microbiome ; Gastrointestinal Tract/*microbiology ; Genomics/methods ; *Host Microbial Interactions ; Humans ; Mice ; *Microbiota ; *Models, Animal ; }, abstract = {The human intestinal ecosystem is characterized by a complex interplay between different microorganisms and the host. The high variation within the human population further complicates the quest toward an adequate understanding of this complex system that is so relevant to human health and well-being. To study host-microbe interactions, defined synthetic bacterial communities have been introduced in gnotobiotic animals or in sophisticated in vitro cell models. This review reinforces that our limited understanding has often hampered the appropriate design of defined communities that represent the human gut microbiota. On top of this, some communities have been applied to in vivo models that differ appreciably from the human host. In this review, the advantages and disadvantages of using defined microbial communities are outlined, and suggestions for future improvement of host-microbe interaction models are provided. With respect to the host, technological advances, such as the development of a gut-on-a-chip system and intestinal organoids, may contribute to more-accurate in vitro models of the human host. With respect to the microbiota, due to the increasing availability of representative cultured isolates and their genomic sequences, our understanding and controllability of the human gut "core microbiota" are likely to increase. Taken together, these advancements could further unravel the molecular mechanisms underlying the human gut microbiota superorganism. Such a gain of insight would provide a solid basis for the improvement of pre-, pro-, and synbiotics as well as the development of new therapeutic microbes.}, }
@article {pmid30863868, year = {2019}, author = {Plantinga, AM and Chen, J and Jenq, RR and Wu, MC}, title = {pldist: ecological dissimilarities for paired and longitudinal microbiome association analysis.}, journal = {Bioinformatics (Oxford, England)}, volume = {35}, number = {19}, pages = {3567-3575}, pmid = {30863868}, issn = {1367-4811}, support = {R01 GM129512/GM/NIGMS NIH HHS/United States ; S10 OD020069/OD/NIH HHS/United States ; F31 AI131595/AI/NIAID NIH HHS/United States ; }, mesh = {Humans ; *Microbiota ; Phylogeny ; Research Design ; }, abstract = {MOTIVATION: The human microbiome is notoriously variable across individuals, with a wide range of 'healthy' microbiomes. Paired and longitudinal studies of the microbiome have become increasingly popular as a way to reduce unmeasured confounding and to increase statistical power by reducing large inter-subject variability. Statistical methods for analyzing such datasets are scarce.<br><br>RESULTS: We introduce a paired UniFrac dissimilarity that summarizes within-individual (or within-pair) shifts in microbiome composition and then compares these compositional shifts across individuals (or pairs). This dissimilarity depends on a novel transformation of relative abundances, which we then extend to more than two time points and incorporate into several phylogenetic and non-phylogenetic dissimilarities. The data transformation and resulting dissimilarities may be used in a wide variety of downstream analyses, including ordination analysis and distance-based hypothesis testing. Simulations demonstrate that tests based on these dissimilarities retain appropriate type 1 error and high power. We apply the method in two real datasets.<br><br>The R package pldist is available on GitHub at https://github.com/aplantin/pldist.<br><br>SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.}, }
@article {pmid30843443, year = {2019}, author = {Salvucci, E}, title = {The human-microbiome superorganism and its modulation to restore health.}, journal = {International journal of food sciences and nutrition}, volume = {70}, number = {7}, pages = {781-795}, doi = {10.1080/09637486.2019.1580682}, pmid = {30843443}, issn = {1465-3478}, mesh = {Bifidobacterium/physiology ; Brain/microbiology ; Dysbiosis ; Gastrointestinal Microbiome/physiology ; Gastrointestinal Tract/microbiology ; *Health ; Host Microbial Interactions/immunology/*physiology ; Humans ; Microbiota/immunology/*physiology ; Neurodevelopmental Disorders/microbiology/prevention &amp; control ; Prebiotics ; Probiotics ; Synbiotics ; }, abstract = {Microbiome is the community of microorganism that co-live with a host. The human being is the result of the integration of its genome and the coexistence with millions of microorganisms throughout its evolutionary history. Human-microbiome association can be considered a step of integration in evolution, constituting a superorganism. Many emergent diseases are related to the loss of part of this microbiome and its restoration can be achieved by different strategies. Gut microbiome imbalance is particularly associated with numerous inflammatory, immune and nervous system-related diseases by a communication pathway called microbiome-brain axis. Modulation of microbiome by administering prebiotics, like arabinoxylans, and synbiotics is a plausible treatment for dysbiosis, the regulation of neurotransmitters and alleviation of neurological manifestations.}, }
@article {pmid30835837, year = {2019}, author = {Haahtela, T}, title = {A biodiversity hypothesis.}, journal = {Allergy}, volume = {74}, number = {8}, pages = {1445-1456}, doi = {10.1111/all.13763}, pmid = {30835837}, issn = {1398-9995}, mesh = {Allergens/immunology ; Animals ; *Biodiversity ; *Disease Susceptibility/immunology ; Environment ; Environmental Exposure ; Finland ; Homeostasis/immunology ; *Host-Pathogen Interactions/immunology ; Humans ; Hypersensitivity/etiology ; Immunoglobulin E/immunology ; *Microbiota/immunology ; }, abstract = {Biodiversity hypothesis states that contact with natural environments enriches the human microbiome, promotes immune balance and protects from allergy and inflammatory disorders. We are protected by two nested layers of biodiversity, microbiota of the outer layer (soil, natural waters, plants, animals) and inner layer (gut, skin, airways). The latter inhabits our body and is colonized from the outer layer. Explosion of human populations along with cultural evolution is profoundly changing our environment and lifestyle. Adaptive immunoregulatory circuits and dynamic homeostasis are at stake in the newly emerged urban surroundings. In allergy, and chronic inflammatory disorders in general, exploring the determinants of immunotolerance is the key for prevention and more effective treatment. Loss of immunoprotective factors, derived from nature, is a new kind of health risk poorly acknowledged until recently. The paradigm change has been implemented in the Finnish allergy programme (2008-2018), which emphasized tolerance instead of avoidance. The first results are promising, as allergy burden has started to reduce. The rapidly urbanizing world is facing serious biodiversity loss with global warming, which are interconnected. Biodiversity hypothesis of health and disease has societal impact, for example, on city planning, food and energy production and nature conservation. It has also a message for individuals for health and well-being: take nature close, to touch, eat, breathe, experience and enjoy. Biodiverse natural environments are dependent on planetary health, which should be a priority also among health professionals.}, }
@article {pmid30835680, year = {2019}, author = {Wallace, DJ and Sayre, NL and Patterson, TT and Nicholson, SE and Hilton, D and Grandhi, R}, title = {Spinal cord injury and the human microbiome: beyond the brain-gut axis.}, journal = {Neurosurgical focus}, volume = {46}, number = {3}, pages = {E11}, doi = {10.3171/2018.12.FOCUS18206}, pmid = {30835680}, issn = {1092-0684}, support = {IK2 BX003240/BX/BLRD VA/United States ; }, mesh = {Animals ; Bacterial Translocation ; Brain Injuries, Traumatic/microbiology ; Burns/microbiology ; Dysbiosis/complications/immunology/microbiology/therapy ; Fecal Microbiota Transplantation ; Feedback, Physiological ; *Gastrointestinal Microbiome ; Humans ; Immunity, Mucosal/immunology ; Intestinal Mucosa/immunology/microbiology ; Mice ; Probiotics/therapeutic use ; Rats ; Sepsis/etiology/microbiology ; Species Specificity ; Spinal Cord Injuries/complications/immunology/*microbiology ; Stroke/microbiology/therapy ; }, abstract = {In addition to standard management for the treatment of the acute phase of spinal cord injury (SCI), implementation of novel neuroprotective interventions offers the potential for significant reductions in morbidity and long-term health costs. A better understanding of the systemic changes after SCI could provide insight into mechanisms that lead to secondary injury. An emerging area of research involves the complex interplay of the gut microbiome and the CNS, i.e., a brain-gut axis, or perhaps more appropriately, a CNS-gut axis. This review summarizes the relevant literature relating to the gut microbiome and SCI. Experimental models in stroke and traumatic brain injury demonstrate the bidirectional communication of the CNS to the gut with postinjury dysbiosis, gastrointestinal-associated lymphoid tissue-mediated neuroinflammatory responses, and bacterial-metabolite neurotransmission. Similar findings are being elucidated in SCI as well. Experimental interventions in these areas have shown promise in improving functional outcomes in animal models. This commensal relationship between the human body and its microbiome, particularly the gut microbiome, represents an exciting frontier in experimental medicine.}, }
@article {pmid30832730, year = {2019}, author = {Meyer, F and Bremges, A and Belmann, P and Janssen, S and McHardy, AC and Koslicki, D}, title = {Assessing taxonomic metagenome profilers with OPAL.}, journal = {Genome biology}, volume = {20}, number = {1}, pages = {51}, pmid = {30832730}, issn = {1474-760X}, mesh = {Classification/methods ; Humans ; Metagenomics/methods/*standards ; *Software ; }, abstract = {The explosive growth in taxonomic metagenome profiling methods over the past years has created a need for systematic comparisons using relevant performance criteria. The Open-community Profiling Assessment tooL (OPAL) implements commonly used performance metrics, including those of the first challenge of the initiative for the Critical Assessment of Metagenome Interpretation (CAMI), together with convenient visualizations. In addition, we perform in-depth performance comparisons with seven profilers on datasets of CAMI and the Human Microbiome Project. OPAL is freely available at https://github.com/CAMI-challenge/OPAL .}, }
@article {pmid30830433, year = {2019}, author = {Piersigilli, F and Lam, TT and Vernocchi, P and Quagliariello, A and Putignani, L and Aghai, ZH and Bhandari, V}, title = {Identification of new biomarkers of bronchopulmonary dysplasia using metabolomics.}, journal = {Metabolomics : Official journal of the Metabolomic Society}, volume = {15}, number = {2}, pages = {20}, pmid = {30830433}, issn = {1573-3890}, mesh = {Biomarkers/analysis/*metabolism ; Bronchopulmonary Dysplasia/*metabolism ; Cluster Analysis ; Discriminant Analysis ; Female ; Gestational Age ; Humans ; Infant, Newborn ; Infant, Premature/metabolism ; Male ; Mass Spectrometry/methods ; Metabolomics/*methods ; Prospective Studies ; }, abstract = {OBJECTIVE: To identify new biomarkers of bronchopulmonary dysplasia (BPD) in preterm neonates.<br><br>STUDY DESIGN: Metabolomic study of prospectively collected tracheal aspirate (TA) samples from preterm neonates admitted in 2 neonatal intensive care units measured by a mass spectroscopy-based assay and analysed using partial least squares-discriminant analysis.<br><br>RESULTS: We evaluated 160 TA samples from 68 neonates, 44 with BPD and 24 without BPD in the first week of life. A cluster of 53 metabolites was identified as characteristic of BPD, with 18 select metabolites being highly significant in the separation of BPD versus No BPD. To control for the gestational age (GA) differences, we did a sub-group analyses, and noted that the amino acids histidine, glutamic acid, citrulline, glycine and isoleucine levels were higher in neonates with BPD. In addition, acylcarnitines C16-OH and C18:1-OH were also higher in neonates who developed BPD, but especially in the most preterm infants (neonates with GA&#x2009;<&#x2009;27 weeks).<br><br>CONCLUSION: Metabolomics is a promising approach to identify novel specific biomarkers for BPD.}, }
@article {pmid30828318, year = {2019}, author = {Reid, G}, title = {Disentangling What We Know About Microbes and Mental Health.}, journal = {Frontiers in endocrinology}, volume = {10}, number = {}, pages = {81}, pmid = {30828318}, issn = {1664-2392}, abstract = {Much has been written in recent years about the gut-brain axis. Exciting pilot studies suggest probiotic applications to the gut can reduce anxiety and depression via the vagus nerve. But not to diminish such findings, much still needs to be considered, including the fact that the vagus nerve links to many other body sites that also host a microbiome. Questions remain that touch the core of being human: (i) Do our microbes influence happiness and to what extent? (ii) What components of the gut microbiota and their function, including as it relates to mental health, are critical and how do they differ between agile, fit hunter gatherers and obese westerners or Danes described as the happiest people on the planet? (iii) What role do environmental pollutants play in this microbes-host ecosystem? While approaching life from a reductionist perspective has a long history in science, we need to try to interrogate these health and disease issues from a wider perspective. For verification of a link between the gut microbiota and brain, and to test new therapies, human studies are needed, and are long overdue.}, }
@article {pmid30814984, year = {2019}, author = {Song, Z and Wang, X and Zhou, X and Jiang, S and Li, Y and Ahmad, O and Qi, L and Li, P and Li, J}, title = {Taxonomic Distribution of FosB in Human-Microbiota and Activity Comparison of Fosfomycin Resistance.}, journal = {Frontiers in microbiology}, volume = {10}, number = {}, pages = {200}, pmid = {30814984}, issn = {1664-302X}, abstract = {FosB, a Mg[2+] dependent thioltransferase, confers antibiotic resistance to fosfomycin through enzymatic drug inactivation. Among all antibiotic resistant proteins in the Antibiotic Resistance Genes Database and the Comprehensive Antibiotic Resistance Database, FosB is within 5% of the most number of ARPs identified in Human Microbiome Project reference database but mainly distributed in limited genera, i.e., 122 of total 133 FosB homologues are found from Bacillus and Staphylococcus. Furthermore, these FosB sequences could be divided into three clusters based on their phylogenetic relationship, i.e., two groups of FosB were mainly from Bacillus, and another was mainly from Staphylococcus. Finally, we confirmed that FosB from the group of Staphylococcus presented the highest resistance ability to fosfomycin by in silico and in vitro comparisons. In summary, this study elaborates the specific taxonomic characteristics and resistant abilities of FosB in human microbiota, which might help in developing more promising fosfomycin-like antibiotics.}, }
@article {pmid30811000, year = {2019}, author = {Shan, Y and Wu, W and Fan, W and Haahtela, T and Zhang, G}, title = {House dust microbiome and human health risks.}, journal = {International microbiology : the official journal of the Spanish Society for Microbiology}, volume = {22}, number = {3}, pages = {297-304}, doi = {10.1007/s10123-019-00057-5}, pmid = {30811000}, issn = {1618-1905}, mesh = {Bacteria/classification/*isolation &amp; purification ; *Dust ; *Environmental Microbiology ; Fungi/classification/*isolation &amp; purification ; Humans ; *Microbiota ; *Risk Assessment ; }, abstract = {People spend a lot of time indoors and the indoor microbiome is a major part of the environment that we are exposed to. However, awareness of the exposure to the indoor microbiome and its health effects remains poor. Outdoor environment (soil and air), indoor sources (ventilation, dampness and building materials), human occupants, and pets compose the indoor microbial community. It has been estimated that up to 500-1000 different species can be present in house dust. House dust is a major source and reservoir of indoor microbiome, which influences human microbiome and determines health and disease. Herein, we review the origins and the components of the fungal and bacterial communities in house dust and their possible effect on human health, in particular on allergic disorders, intestinal microbiome, and immune responses. We expect to lay a solid foundation for the further study on the mechanisms of how the house dust microbes interact with the host microbiome and the human immune system.}, }
@article {pmid30810508, year = {2019}, author = {Falony, G and Vandeputte, D and Caenepeel, C and Vieira-Silva, S and Daryoush, T and Vermeire, S and Raes, J}, title = {The human microbiome in health and disease: hype or hope.}, journal = {Acta clinica Belgica}, volume = {74}, number = {2}, pages = {53-64}, doi = {10.1080/17843286.2019.1583782}, pmid = {30810508}, issn = {2295-3337}, mesh = {Colon/microbiology ; Disease ; Fecal Microbiota Transplantation ; Feces/microbiology ; *Gastrointestinal Microbiome ; Humans ; }, abstract = {OBJECTIVES: The prognostic, diagnostic, and therapeutic potential of the human gut microbiota is widely recognised. However, translation of microbiome findings to clinical practice is challenging. Here, we discuss current knowledge and applications in the field.<br><br>METHODS: We revisit some recent advances in the field of faecal microbiome analyses with a focus on covariate analyses and ecological interpretation.<br><br>RESULTS: Population-level characterization of gut microbiota variation among healthy volunteers has allowed identifying microbiome covariates required for clinical studies. Currently, microbiome research is moving from relative to quantitative approaches that will shed a new light on microbiota-host interactions in health and disease.<br><br>CONCLUSIONS: Covariate characterization and technical advances increase reproducibility of microbiome research. Targeted in vitro/in vivo intervention studies will accelerate clinical implementation of microbiota findings.}, }
@article {pmid30808411, year = {2019}, author = {, }, title = {A review of 10 years of human microbiome research activities at the US National Institutes of Health, Fiscal Years 2007-2016.}, journal = {Microbiome}, volume = {7}, number = {1}, pages = {31}, pmid = {30808411}, issn = {2049-2618}, mesh = {Biomedical Research/*economics/*organization &amp; administration ; Humans ; Metagenomics/economics/organization &amp; administration ; Microbiota ; National Institutes of Health (U.S.) ; United States ; }, abstract = {The National Institutes of Health (NIH) is the primary federal government agency for biomedical research in the USA. NIH provides extensive support for human microbiome research with 21 of 27 NIH Institutes and Centers (ICs) currently funding this area through their extramural research programs. This analysis of the NIH extramural portfolio in human microbiome research briefly reviews the early history of this field at NIH, summarizes the program objectives and the resources developed in the recently completed 10-year (fiscal years 2007-2016) $215 M Human Microbiome Project (HMP) program, evaluates the scope and range of the $728 M NIH investment in extramural human microbiome research activities outside of the HMP over fiscal years 2012-2016, and highlights some specific areas of research which emerged from this investment. This analysis closes with a few comments on the technical needs and knowledge gaps which remain for this field to be able to advance over the next decade and for the outcomes of this research to be able to progress to microbiome-based interventions for treating disease and supporting health.}, }
@article {pmid30808401, year = {2019}, author = {, }, title = {2017 NIH-wide workshop report on "The Human Microbiome: Emerging Themes at the Horizon of the 21st Century".}, journal = {Microbiome}, volume = {7}, number = {1}, pages = {32}, pmid = {30808401}, issn = {2049-2618}, support = {U54 DE023789/DE/NIDCR NIH HHS/United States ; U54 DK102557/DK/NIDDK NIH HHS/United States ; P30 CA008748/CA/NCI NIH HHS/United States ; P30 CA014236/CA/NCI NIH HHS/United States ; U54 HD080784/HD/NICHD NIH HHS/United States ; R24 DK110499/DK/NIDDK NIH HHS/United States ; }, mesh = {Humans ; Internet ; *Microbiota ; National Institutes of Health (U.S.) ; United States ; }, abstract = {The National Institutes of Health (NIH) organized a three-day human microbiome research workshop, August 16-18, 2017, to highlight the accomplishments of the 10-year Human Microbiome Project program, the outcomes of the investments made by the 21 NIH Institutes and Centers which now fund this area, and the technical challenges and knowledge gaps which will need to be addressed in order for this field to advance over the next 10 years. This report summarizes the key points in the talks, round table discussions, and Joint Agency Panel from this workshop.}, }
@article {pmid30804923, year = {2018}, author = {Ma, ZS and Li, L}, title = {Semen Microbiome Biogeography: An Analysis Based on a Chinese Population Study.}, journal = {Frontiers in microbiology}, volume = {9}, number = {}, pages = {3333}, pmid = {30804923}, issn = {1664-302X}, abstract = {Investigating inter-subject heterogeneity (or spatial distribution) of human semen microbiome diversity is of important significance. Theoretically, the spatial distribution of biodiversity constitutes the core of microbiome biogeography. Practically, the inter-subject heterogeneity is crucial for understanding the normal (healthy) flora of semen microbiotas as well as their possible changes associated with abnormal fertility. In this article, we analyze the scaling (changes) of semen microbiome diversity across individuals with DAR (diversity-area relationship) analysis, a recent extension to classic SAR (species-area relationship) law in biogeography and ecology. Specifically, the unit of "area" is individual subject, and the microbial diversity in seminal fluid of an individual (area) is assessed via metagenomic DNA sequencing technique and measured in the Hill numbers. The DAR models were then fitted to the accrued diversity across different number of individuals (area size). We further tested the difference in DAR parameters among the healthy, subnormal, and abnormal microbiome samples in terms of their fertility status based on a cross-sectional study of a Chinese cohort. Given that no statistically significant differences in the DAR parameters were detected among the three groups, we built unified DAR models for semen microbiome by combining the healthy, subnormal, and abnormal groups. The model parameters were used to (i) estimate the microbiome diversity scaling in a population (cohort), and construct the so-termed DAR profile; (ii) predict/construct the maximal accrual diversity (MAD) profile in a population; (iii) estimate the pair-wise diversity overlap (PDO) between two individuals and construct the PDO profile; (iv) assess the ratio of individual diversity to population (RIP) accrual diversity. The last item (RIP) is a new concept we propose in this study, which is essentially a ratio of local diversity to regional or global diversity (LRD/LGD), applicable to general biodiversity investigation beyond human microbiome.}, }
@article {pmid30801627, year = {2019}, author = {McSkimming, DI and Banack, HR and Genco, R and Wactawski-Wende, J and LaMonte, MJ}, title = {RE: "QUANTIFICATION OF HUMAN MICROBIOME STABILITY OVER 6 MONTHS: IMPLICATIONS FOR EPIDEMIOLOGIC STUDIES".}, journal = {American journal of epidemiology}, volume = {188}, number = {4}, pages = {807-808}, doi = {10.1093/aje/kwz021}, pmid = {30801627}, issn = {1476-6256}, mesh = {Epidemiologic Studies ; Humans ; *Microbiota ; }, }
@article {pmid30799264, year = {2019}, author = {De Filippis, F and Pasolli, E and Tett, A and Tarallo, S and Naccarati, A and De Angelis, M and Neviani, E and Cocolin, L and Gobbetti, M and Segata, N and Ercolini, D}, title = {Distinct Genetic and Functional Traits of Human Intestinal Prevotella copri Strains Are Associated with Different Habitual Diets.}, journal = {Cell host &amp; microbe}, volume = {25}, number = {3}, pages = {444-453.e3}, doi = {10.1016/j.chom.2019.01.004}, pmid = {30799264}, issn = {1934-6069}, mesh = {Diet/*methods ; *Feeding Behavior ; Female ; Gastrointestinal Microbiome ; Genome, Bacterial ; Genotype ; Healthy Volunteers ; Humans ; Italy ; Male ; *Microbiota ; Phenotype ; Prevalence ; Prevotella/*classification/genetics/*isolation &amp; purification/physiology ; }, abstract = {The role of intestinal Prevotella species in human health is controversial, with both positive and negative associations. Strain-level diversity may contribute to discrepancies in genus and species associations with health and disease. We dissected the gut metagenomes of Italians with varying dietary habits, investigating the presence of distinct Prevotella copri strains. Fiber-rich diets were linked to P. copri types with enhanced potential for carbohydrate catabolism. P. copri strains associated with an omnivore diet had a higher prevalence of the leuB gene-involved in branched-chain amino acid biosynthesis-a risk factor for glucose intolerance and type 2 diabetes. These P. copri pangenomes were compared to existing cohorts, providing evidence of distinct gene repertoires characterizing different P. copri populations, with drug metabolism and complex carbohydrate degradation significantly associated with Western and non-Western individuals, respectively. Strain-level P. copri diversity in gut microbiomes is affected by diet and should be considered when examining host-microbe associations.}, }
@article {pmid30799003, year = {2019}, author = {Rogers, GB and Ward, J and Brown, A and Wesselingh, SL}, title = {Inclusivity and equity in human microbiome research.}, journal = {Lancet (London, England)}, volume = {393}, number = {10173}, pages = {728-729}, doi = {10.1016/S0140-6736(18)33204-5}, pmid = {30799003}, issn = {1474-547X}, mesh = {Humans ; *Biomedical Research/standards ; Health Status Disparities ; *Microbiota/genetics ; Racial Groups ; }, }
@article {pmid30777586, year = {2019}, author = {Araos, R and D'Agata, EMC}, title = {The human microbiota and infection prevention.}, journal = {Infection control and hospital epidemiology}, volume = {40}, number = {5}, pages = {585-589}, doi = {10.1017/ice.2019.28}, pmid = {30777586}, issn = {1559-6834}, support = {K24 AI119158/AI/NIAID NIH HHS/United States ; }, mesh = {Anti-Infective Agents/therapeutic use ; *Communicable Disease Control ; Communicable Diseases/microbiology ; Dysbiosis ; Gastrointestinal Microbiome ; Humans ; *Microbiota/drug effects/genetics/physiology ; RNA, Ribosomal, 16S ; }, abstract = {The human microbiome participates in numerous aspects of human physiology and disease states. Recently, studies have begun to explore the role of the microbiome in colonization, infection and transmission of pathogens. This review provides a summary of the methodological principles used in microbiome studies and the published evidence of the impact of microbiome dysbiosis in infection prevention.}, }
@article {pmid30772579, year = {2019}, author = {Li, H and Zhou, XY and Yang, XR and Zhu, YG and Hong, YW and Su, JQ}, title = {Spatial and seasonal variation of the airborne microbiome in a rapidly developing city of China.}, journal = {The Science of the total environment}, volume = {665}, number = {}, pages = {61-68}, doi = {10.1016/j.scitotenv.2019.01.367}, pmid = {30772579}, issn = {1879-1026}, mesh = {*Air Microbiology ; Air Pollutants/*analysis ; Air Pollution/*statistics &amp; numerical data ; Bacteria ; China ; Cities ; Climate ; *Environmental Monitoring ; Firmicutes ; *Microbiota ; Proteobacteria ; RNA, Ribosomal, 16S ; Seasons ; Urbanization ; }, abstract = {Exposure to airborne microbes (AM) can affect the human microbiome and has various consequences for human health. Investigating the profiles of AM and the potential bacterial pathogens within, along with the factors influencing their community, is pivotal for understanding the impact of AM on human health. In this study, we collected AM during spring and summer from 11 sites with various levels of urbanization in the city of Xiamen, China. Bacterial community compositions of the AM were determined based on 16S rRNA gene amplicon sequencing. Firmicutes and Proteobacteria were the predominating phyla in the airborne bacterial communities, and a higher (P < 0.05) diversity of AM was found during the summer as compared to the spring. Significant differences in the community structure of the AM and the potential bacterial pathogens within airborne microbes were observed among the seasons and the sites with different levels of urbanization. Increases and/or decreases in the abundance of Bacillus and Acinetobacter could explain a major part of the variations in the AM community compositions. The proportion of potential bacterial pathogens during the summer was significantly higher (P < 0.01) than in the spring, and the relative abundance of several bacterial pathogens (i.e. Burkholderia multivoran, Enterococcus faecium and Streptococcus thermophilus) related to human diseases (39.8% of total pathogens on average) increased with increasing urbanization levels, suggesting that urbanization can increase the AM-associated human health risk.}, }
@article {pmid30767956, year = {2019}, author = {Bai, J and Jhaney, I and Daniel, G and Watkins Bruner, D}, title = {Pilot Study of Vaginal Microbiome Using QIIME 2™ in Women With Gynecologic Cancer Before and After Radiation Therapy.}, journal = {Oncology nursing forum}, volume = {46}, number = {2}, pages = {E48-E59}, doi = {10.1188/19.ONF.E48-E59}, pmid = {30767956}, issn = {1538-0688}, support = {K99 NR017897/NR/NINR NIH HHS/United States ; }, mesh = {Adult ; Aged ; Female ; Genital Neoplasms, Female/*microbiology/*radiotherapy ; Georgia ; Humans ; Microbiota/*genetics/*radiation effects ; Middle Aged ; Pilot Projects ; RNA, Ribosomal, 16S/*analysis ; Vagina/*microbiology ; }, abstract = {OBJECTIVES: To characterize the vaginal microbiome using QIIME 2™ (Quantitative Insights Into Microbial Ecology 2) in women with gynecologic cancer.<br><br>SAMPLE &amp;AMP; SETTING: 19 women with gynecologic cancer before and after radiation therapy at a comprehensive cancer center in Atlanta, Georgia.<br><br>METHODS &amp;AMP; VARIABLES: This pilot study analyzed vaginal microbiome communities using a microbiome analysis pipeline, beginning with 16S rRNA gene sequencing and processing through use of a bioinformatics pipeline to downstream microbial statistical analysis.<br><br>RESULTS: The findings showed the methods to be robust, and most women with gynecologic cancer showed depletion of Lactobacillus. Compared to those pre-radiation therapy, women post-radiation therapy showed higher abundances of Mobiluncus, Atopobium, and Prevotella but lower abundances of Lactobacillus, Gardnerella, and Peptostreptococcus, which are associated with bacterial vaginosis.<br><br>IMPLICATIONS FOR NURSING: This study presents the fundamentals of human microbiome data collection and analysis methods to inform nursing science. Assessing the vaginal microbiome provides a potential pathway to develop interventions to ameliorate dysbiosis of the vaginal microbiome.}, }
@article {pmid30764863, year = {2019}, author = {Luo, Z and Li, M and Wu, Y and Meng, Z and Martin, L and Zhang, L and Ogunrinde, E and Zhou, Z and Qin, S and Wan, Z and Westerink, MAJ and Warth, S and Liu, H and Jin, P and Stroncek, D and Li, QZ and Wang, E and Wu, X and Heath, SL and Li, Z and Alekseyenko, AV and Jiang, W}, title = {Systemic translocation of Staphylococcus drives autoantibody production in HIV disease.}, journal = {Microbiome}, volume = {7}, number = {1}, pages = {25}, pmid = {30764863}, issn = {2049-2618}, support = {P30 AI027767/AI/NIAID NIH HHS/United States ; R01 AI091526/AI/NIAID NIH HHS/United States ; R01 AI128864/AI/NIAID NIH HHS/United States ; R01 AI114380/AI/NIAID NIH HHS/United States ; R01 CA213290/CA/NCI NIH HHS/United States ; P01 CA186866/CA/NCI NIH HHS/United States ; R01 LM012517/LM/NLM NIH HHS/United States ; I01 CX001211/CX/CSRD VA/United States ; R01 AG045973/AG/NIA NIH HHS/United States ; UL1 TR001450/TR/NCATS NIH HHS/United States ; }, mesh = {Animals ; Autoantibodies/blood/*metabolism ; *Bacterial Translocation ; DNA, Bacterial/blood ; DNA, Ribosomal/blood ; Disease Models, Animal ; Germinal Center/immunology ; HIV Infections/*immunology ; Hep G2 Cells ; Humans ; Immunity, Innate ; Influenza Vaccines/*immunology ; Influenza, Human/prevention &amp; control ; Lymphocyte Activation ; Male ; Mice ; Single-Cell Analysis ; Staphylococcus/genetics/immunology/*physiology ; Up-Regulation ; }, abstract = {BACKGROUND: Increased autoreactive antibodies have been reported in HIV disease; however, the mechanism accounting for autoantibody induction in HIV remains unknown.<br><br>RESULTS: Herein, we show that seasonal influenza vaccination induces autoantibody production (e.g., IgG anti-nuclear antibody (ANA) and anti-double-stranded DNA antibody (anti-dsDNA)) in some viral-suppressed antiretroviral therapy (ART)-treated HIV+ subjects, but not in healthy controls. These autoantibodies were not derived from antigen-specific B cells but from activated "bystander" B cells analyzed by single-cell assay and by study of purified polyclonal ANAs from plasma. To explore the mechanism of autoantibody generation in HIV+ subjects, plasma level of microbial products, gene expression profile of B cells, and B cell receptor (BCR) repertoires were analyzed. We found that autoantibody production was associated with increased plasma level of microbial translocation; the patients with high autoantibodies had skewed B cell repertoires and upregulation of genes related to innate immune activation in response to microbial translocation. By analyzing circulating microbial 16S rDNA in plasma, the relative abundance of Staphylococcus was found to be associated with autoantibody production in HIV+ subjects. Finally, we found that injection of heat-killed Staphylococcus aureus promoted germinal center B cell responses and autoantibody production in mice, consistent with the notion that autoantibody production in HIV+ patients is triggered by microbial products.<br><br>CONCLUSIONS: Our results showed that translocation of Staphylococcus can promote B cell activation through enhancing germinal center response and induces autoantibody production. It uncovers a potential mechanism linking microbial translocation and autoimmunity in HIV+ disease and provides a strong rationale for targeting Staphylococcus to prevent autoantibody production.}, }
@article {pmid30763534, year = {2019}, author = {Shkoporov, AN and Hill, C}, title = {Bacteriophages of the Human Gut: The "Known Unknown" of the Microbiome.}, journal = {Cell host &amp; microbe}, volume = {25}, number = {2}, pages = {195-209}, doi = {10.1016/j.chom.2019.01.017}, pmid = {30763534}, issn = {1934-6069}, mesh = {Bacteria/*virology ; Bacteriophages/*classification/*growth &amp; development ; Gastrointestinal Tract/*microbiology/*virology ; Host-Parasite Interactions ; Humans ; *Microbiota ; Population Dynamics ; }, abstract = {The human gut microbiome is a dense and taxonomically diverse consortium of microorganisms. While the bacterial components of the microbiome have received considerable attention, comparatively little is known about the composition and physiological significance of human gut-associated bacteriophage populations (phageome). By extrapolating our knowledge of phage-host interactions from other environments, one could expect that >10[12] viruses reside in the human gut, and we can predict that they play important roles in regulating the complex microbial networks operating in this habitat. Before delving into their function, we need to first overcome the challenges associated with studying and characterizing the phageome. In this Review, we summarize the available methods and main findings regarding taxonomic composition, community structure, and population dynamics in the human gut phageome. We also discuss the main challenges in the field and identify promising avenues for future research.}, }
@article {pmid30759766, year = {2019}, author = {Reddel, S and Putignani, L and Del Chierico, F}, title = {The Impact of Low-FODMAPs, Gluten-Free, and Ketogenic Diets on Gut Microbiota Modulation in Pathological Conditions.}, journal = {Nutrients}, volume = {11}, number = {2}, pages = {}, pmid = {30759766}, issn = {2072-6643}, mesh = {*Diet, Gluten-Free ; *Diet, Ketogenic ; *Dietary Carbohydrates ; Gastrointestinal Diseases/*diet therapy/microbiology ; *Gastrointestinal Microbiome ; Humans ; }, abstract = {The gut microbiota performs several essential protective, structural, and metabolic functions for host health. The maintenance of a beneficial microbiota requires a homeostatic equilibrium within microbial communities, and between the microorganisms and the host. The gut microbiota composition may be affected by external factors, among them diet habits may be considered most important. In some pathological conditions such as irritable bowel syndrome (IBS), celiac disease (CD), or neurological disorders (ND), specific dietary regimens as low-fermentable, oligo-, di-, mono-saccharides and polyols (FODMAPs), ketogenic (KD), and gluten-free (GFD) diets are considered therapeutic. These kinds of diets are characterized by a reduction or exclusion of a specific nutrient from the entire dietary pattern. Despite these alimentary regimens showing beneficial effects on disease symptoms, they can affect microbiota composition, especially if they are protracted for a long time. To date, only a few studies have reported the effects of these diets on gut microbiota. In this review, we discuss the effects of low-FODMAPs, KD, and GFD on gut microbiota modulation in pathological conditions, advancing the possibility of depicting a balanced diet and developing personalized dietary intervention protocols.}, }
@article {pmid30744677, year = {2019}, author = {Blakeley-Ruiz, JA and Erickson, AR and Cantarel, BL and Xiong, W and Adams, R and Jansson, JK and Fraser, CM and Hettich, RL}, title = {Metaproteomics reveals persistent and phylum-redundant metabolic functional stability in adult human gut microbiomes of Crohn's remission patients despite temporal variations in microbial taxa, genomes, and proteomes.}, journal = {Microbiome}, volume = {7}, number = {1}, pages = {18}, pmid = {30744677}, issn = {2049-2618}, support = {UH2 DK083991/DK/NIDDK NIH HHS/United States ; }, mesh = {Acetylglucosamine/analysis ; Adult ; Bacteria/genetics/*metabolism ; Crohn Disease/*microbiology/surgery ; Cytidine Monophosphate N-Acetylneuraminic Acid/analysis ; Fatty Acids, Volatile/analysis ; Feces/microbiology ; Female ; Gastrointestinal Microbiome/genetics/*physiology ; Humans ; Male ; Middle Aged ; Proteome/*metabolism ; Proteomics ; RNA, Ribosomal, 16S/genetics ; }, abstract = {BACKGROUND: The gut microbiome plays a fundamental role in the human host's overall health by contributing key biological functions such as expanded metabolism and pathogen defense/immune control. In a healthy individual, the gut microbiome co-exists within the human host in a symbiotic, non-inflammatory relationship that enables mutual benefits, such as microbial degradation of indigestible food products into small molecules that the host can utilize, and enhanced pathogen defense. In abnormal conditions, such as Crohn's disease, this favorable metabolic relationship breaks down and a variety of undesirable activities result, including chronic inflammation and other health-related issues. It has been difficult, however, to elucidate the overall functional characteristics of this relationship because the microbiota can vary substantially in composition for healthy humans and possibly even more in individuals with gut disease conditions such as Crohn's disease. Overall, this suggests that microbial membership composition may not be the best way to characterize a phenotype. Alternatively, it seems to be more informative to examine and characterize the functional composition of a gut microbiome. Towards that end, this study examines 25 metaproteomes measured in several Crohn's disease patients' post-resection surgery across the course of 1 year, in order to examine persistence of microbial taxa, genes, proteins, and metabolic functional distributions across time in individuals whose microbiome might be more variable due to the gut disease condition.<br><br>RESULTS: The measured metaproteomes were highly personalized, with all the temporally-related metaproteomes clustering most closely by individual. In general, the metaproteomes were remarkably distinct between individuals and to a lesser extent within individuals. This prompted a need to characterize the metaproteome at a higher functional level, which was achieved by annotating identified protein groups with KEGG orthologous groups to infer metabolic modules. At this level, similar and redundant metabolic functions across multiple phyla were observed across time and between individuals. Tracking through these various metabolic modules revealed a clear path from carbohydrate, lipid, and amino acid degradation to central metabolism and finally the production of fermentation products.<br><br>CONCLUSIONS: The human gut metaproteome can vary quite substantially across time and individuals. However, despite substantial intra-individual variation in the metaproteomes, there is a clear persistence of conserved metabolic functions across time and individuals. Additionally, the persistence of these core functions is redundant across multiple phyla but is not always observable in the same sample. Finally, the gut microbiome's metabolism is not driven by a set of discrete linear pathways but a web of interconnected reactions facilitated by a network of enzymes that connect multiple molecules across multiple pathways.}, }
@article {pmid30732955, year = {2019}, author = {Healy, CM and Moran, GP}, title = {The microbiome and oral cancer: More questions than answers.}, journal = {Oral oncology}, volume = {89}, number = {}, pages = {30-33}, doi = {10.1016/j.oraloncology.2018.12.003}, pmid = {30732955}, issn = {1879-0593}, mesh = {Carcinoma, Squamous Cell/*genetics/pathology ; Humans ; Microbiota/*genetics ; Mouth Neoplasms/*genetics/pathology ; }, abstract = {Recent advances in DNA sequencing technology have facilitated rapid advances in the analysis of the human microbiome and its role in human disease. Several studies have now shown that OSCC and some oral premalignant conditions are associated with alterations in the oral microbiome. These studies raise questions regarding the role of the oral microbiome in the progression of oral malignancies and whether microbiome change is a significant risk factor in the development of oral cancer. This short review summarises current knowledge in the field and highlights questions that require further investigation.}, }
@article {pmid30731251, year = {2019}, author = {Bekker, V and Zwittink, RD and Knetsch, CW and Sanders, IMJG and Berghuis, D and Heidt, PJ and Vossen, JMJJ and de Vos, WM and Belzer, C and Bredius, RGM and Van't Hof, PJ and Lankester, AC and Kuijper, EJ}, title = {Dynamics of the Gut Microbiota in Children Receiving Selective or Total Gut Decontamination Treatment during Hematopoietic Stem Cell Transplantation.}, journal = {Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation}, volume = {25}, number = {6}, pages = {1164-1171}, doi = {10.1016/j.bbmt.2019.01.037}, pmid = {30731251}, issn = {1523-6536}, mesh = {Adolescent ; Child ; Child, Preschool ; Decontamination ; Female ; Gastrointestinal Microbiome/*drug effects ; Hematopoietic Stem Cell Transplantation/*methods ; Humans ; Male ; Microbiota/*drug effects ; Prospective Studies ; Transplantation Conditioning/*methods ; }, abstract = {Bloodstream infections and graft-versus-host disease are common complications after hematopoietic stem cell transplantation (HSCT) procedures, associated with the gut microbiota that acts as a reservoir for opportunistic pathogens. Selective gut decontamination (SGD) and total gut decontamination (TGD) during HSCT have been associated with a decreased risk of developing these complications after transplantation. However, because studies have shown conflicting results, the use of these treatments remains subject of debate. In addition, their impact on the gut microbiota is not well studied. The aim of this study was to elucidate the dynamics of the microbiota during and after TGD and to compare these with the dynamics of SGD. In this prospective, observational, single-center study fecal samples were longitudinally collected from 19 children eligible for allogenic HSCT (TGD, n=12; SGD, n=7), weekly during hospital admission and monthly after discharge. In addition, fecal samples were collected from 3 family stem cell donors. Fecal microbiota structure of patients and donors was determined by 16S rRNA gene amplicon sequencing. Microbiota richness and diversity markedly decreased during SGD and TGD and gradually increased after cessation of decontamination treatment. During SGD, gut microbiota composition was relatively stable and dominated by Bacteroides, whereas it showed high inter- and intraindividual variation and low Bacteroides abundance during TGD. In some children TGD allowed the genera Enterococcus and Streptococcus to thrive during treatment. A gut microbiota dominated by Bacteroides was associated with increased predicted activity of several metabolic processes. Comparing the microbiota of recipients and their donors indicated that receiving an SCT did not alter the patient's microbiota to become more similar to that of its donor. Overall, our findings indicate that SGD and TGD affect gut microbiota structure in a treatment-specific manner. Whether these treatments affect clinical outcomes via interference with the gut microbiota needs to be further elucidated.}, }
@article {pmid30728915, year = {2019}, author = {Lu, H and Ren, Z and Li, A and Li, J and Xu, S and Zhang, H and Jiang, J and Yang, J and Luo, Q and Zhou, K and Zheng, S and Li, L}, title = {Tongue coating microbiome data distinguish patients with pancreatic head cancer from healthy controls.}, journal = {Journal of oral microbiology}, volume = {11}, number = {1}, pages = {1563409}, pmid = {30728915}, issn = {2000-2297}, abstract = {Background: The microbiota plays a critical role in the process of human carcinogenesis. Pancreatic head carcinoma (PHC)-associated tongue coating microbiome dysbiosis has not yet been clearly defined.Objective: Our aim is to reveal the bacterial composition shifts in the microbiota of the tongue coat of PHC patients.Design: The tongue coating microbiota was analyzed in 30 PHC patients and 25 healthy controls using 16S rRNA gene sequencing technology.Results: The microbiome diversity of the tongue coat in PHC patients was significantly increased, as shown by the Shannon, Simpson, inverse Simpson, Obs and incidence-based coverage estimators. Principal component analysis revealed that PHC patients were colonized by remarkably different tongue coating microbiota than healthy controls and liver cancer patients. Linear discriminant analysis effect size revealed that Leptotrichia, Fusobacterium,Rothia, Actinomyces, Corynebacterium, Atopobium, Peptostreptococcus, Catonella, Oribacterium, Filifactor, Campylobacter, Moraxella and Tannerella were overrepresented in the tongue coating of PHC patients, and Haemophilus, Porphyromonas and Paraprevotella were enriched in the tongue coating microbiota of healthy controls. Strikingly, Haemophilus, Porphyromonas, Leptotrichia and Fusobacterium could distinguish PHC patients from healthy subjects, and Streptococcus and SR1 could distinguish PHC patients from liver cancer patients. Conclusions: These findings identified the microbiota dysbiosis of the tongue coat in PHC patients, and provide insight into the association between the human microbiome and pancreatic cancer.}, }
@article {pmid30725462, year = {2019}, author = {Morales, E and Chen, J and Greathouse, KL}, title = {Compositional Analysis of the Human Microbiome in Cancer Research.}, journal = {Methods in molecular biology (Clifton, N.J.)}, volume = {1928}, number = {}, pages = {299-335}, doi = {10.1007/978-1-4939-9027-6_16}, pmid = {30725462}, issn = {1940-6029}, mesh = {Biological Evolution ; Gastrointestinal Microbiome ; Humans ; *Metagenome ; *Metagenomics/methods ; *Microbiota ; Polymerase Chain Reaction ; RNA, Ribosomal, 16S ; *Research ; }, abstract = {Gut microbial composition has shown to be associated with obesity, diabetes mellitus, inflammatory bowel disease, colitis, autoimmune disorders, and cancer, among other diseases. Microbiome research has significantly evolved through the years and continues to advance as we develop new and better strategies to more accurately measure its composition and function. Careful selection of study design, inclusion and exclusion criteria of participants, and methodology are paramount to accurately analyze microbial structure. Here we present the most up-to-date available information on methods for gut microbial collection and analysis.}, }
@article {pmid30718869, year = {2019}, author = {Forster, SC and Kumar, N and Anonye, BO and Almeida, A and Viciani, E and Stares, MD and Dunn, M and Mkandawire, TT and Zhu, A and Shao, Y and Pike, LJ and Louie, T and Browne, HP and Mitchell, AL and Neville, BA and Finn, RD and Lawley, TD}, title = {A human gut bacterial genome and culture collection for improved metagenomic analyses.}, journal = {Nature biotechnology}, volume = {37}, number = {2}, pages = {186-192}, pmid = {30718869}, issn = {1546-1696}, support = {/WT_/Wellcome Trust/United Kingdom ; 098051/WT_/Wellcome Trust/United Kingdom ; }, mesh = {Bacteria/classification ; Computational Biology/methods ; Contig Mapping ; Gastrointestinal Microbiome ; *Genome, Bacterial ; Genome, Human ; Humans ; *Metagenome ; *Metagenomics ; Phylogeny ; RNA, Ribosomal, 16S/metabolism ; Sequence Analysis, DNA ; Species Specificity ; }, abstract = {Understanding gut microbiome functions requires cultivated bacteria for experimental validation and reference bacterial genome sequences to interpret metagenome datasets and guide functional analyses. We present the Human Gastrointestinal Bacteria Culture Collection (HBC), a comprehensive set of 737 whole-genome-sequenced bacterial isolates, representing 273 species (105 novel species) from 31 families found in the human gastrointestinal microbiota. The HBC increases the number of bacterial genomes derived from human gastrointestinal microbiota by 37%. The resulting global Human Gastrointestinal Bacteria Genome Collection (HGG) classifies 83% of genera by abundance across 13,490 shotgun-sequenced metagenomic samples, improves taxonomic classification by 61% compared to the Human Microbiome Project (HMP) genome collection and achieves subspecies-level classification for almost 50% of sequences. The improved resource of gastrointestinal bacterial reference sequences circumvents dependence on de novo assembly of metagenomes and enables accurate and cost-effective shotgun metagenomic analyses of human gastrointestinal microbiota.}, }
@article {pmid30710104, year = {2019}, author = {Du Toit, A}, title = {Expanding diversity of the human microbiome.}, journal = {Nature reviews. Microbiology}, volume = {17}, number = {3}, pages = {126}, doi = {10.1038/s41579-019-0154-0}, pmid = {30710104}, issn = {1740-1534}, }
@article {pmid30705670, year = {2018}, author = {Whittle, E and Leonard, MO and Harrison, R and Gant, TW and Tonge, DP}, title = {Multi-Method Characterization of the Human Circulating Microbiome.}, journal = {Frontiers in microbiology}, volume = {9}, number = {}, pages = {3266}, pmid = {30705670}, issn = {1664-302X}, abstract = {The term microbiome describes the genetic material encoding the various microbial populations that inhabit our body. Whilst colonization of various body niches (e.g., the gut) by dynamic communities of microorganisms is now universally accepted, the existence of microbial populations in other "classically sterile" locations, including the blood, is a relatively new concept. The presence of bacteria-specific DNA in the blood has been reported in the literature for some time, yet the true origin of this is still the subject of much deliberation. The aim of this study was to investigate the phenomenon of a "blood microbiome" by providing a comprehensive description of bacterially derived nucleic acids using a range of complementary molecular and classical microbiological techniques. For this purpose we utilized a set of plasma samples from healthy subjects (n = 5) and asthmatic subjects (n = 5). DNA-level analyses involved the amplification and sequencing of the 16S rRNA gene. RNA-level analyses were based upon the de novo assembly of unmapped mRNA reads and subsequent taxonomic identification. Molecular studies were complemented by viability data from classical aerobic and anaerobic microbial culture experiments. At the phylum level, the blood microbiome was predominated by Proteobacteria, Actinobacteria, Firmicutes, and Bacteroidetes. The key phyla detected were consistent irrespective of molecular method (DNA vs. RNA), and consistent with the results of other published studies. In silico comparison of our data with that of the Human Microbiome Project revealed that members of the blood microbiome were most likely to have originated from the oral or skin communities. To our surprise, aerobic and anaerobic cultures were positive in eight of out the ten donor samples investigated, and we reflect upon their source. Our data provide further evidence of a core blood microbiome, and provide insight into the potential source of the bacterial DNA/RNA detected in the blood. Further, data reveal the importance of robust experimental procedures, and identify areas for future consideration.}, }
@article {pmid30701191, year = {2019}, author = {Leviatan, S and Segal, E}, title = {A Significant Expansion of Our Understanding of the Composition of the Human Microbiome.}, journal = {mSystems}, volume = {4}, number = {1}, pages = {}, pmid = {30701191}, issn = {2379-5077}, abstract = {Shotgun sequencing of samples taken from the human microbiome often reveals only partial mapping of the sequenced metagenomic reads to existing reference genomes. Such partial mappability indicates that many genomes are missing in our reference genome set. This is particularly true for non-Western populations and for samples that do not originate from the gut. Pasolli et al. (E. Pasolli, F. Asnicar, S. Manara, M. Zolfo, et al., Cell, 2019, https://doi.org/10.1016/j.cell.2019.01.001) perform a grand effort to expand the reference set, and to better classify its members, revealing a wider pangenome of existing species as well as identifying new species of previously unknown taxonomic branches.}, }
@article {pmid30700742, year = {2019}, author = {Tejesvi, MV and Nissi, R and Saravesi, K and Pirttilä, AM and Markkola, A and Talvensaari-Mattila, A and Ruotsalainen, AL}, title = {Association of prevalent vaginal microbiome of mother with occurrence of type I diabetes in child.}, journal = {Scientific reports}, volume = {9}, number = {1}, pages = {959}, pmid = {30700742}, issn = {2045-2322}, mesh = {Adult ; Biodiversity ; Case-Control Studies ; Child ; Child, Preschool ; Diabetes Mellitus, Type 1/*etiology ; Female ; Humans ; Infant ; Infant, Newborn ; *Microbiota ; *Mothers ; Vagina/*microbiology ; Young Adult ; }, abstract = {Type I diabetes (T1D) is a rapidly increasing autoimmune disease especially in the Western countries and poses a serious global health problem. Incidence of T1D cannot be fully explained by genetic background, and environmental factors have been assumed to play a role. Environmental conditions and composition of human microbiome have been found to correlate with the incidence of T1D. We asked whether mothers' prevalent vaginal microbiome could correlate with the incidence of T1D in child. To test this hypothesis, we collected samples of vaginal microbiomes from eight mothers that had at least one child with T1D (child age maximum of 11 years at the time of sampling), born with a vaginal delivery. Eight control mothers had child/children with vaginal delivery and no diabetic child/children. The microbiomes were studied by using 16S rRNA Ion Torrent high throughput sequencing. We found that composition of total and Lactobacillus microbiome was altered, and saw an indication that diversity of vaginal microbiomes of the mothers with a diabetic child could be higher. Based on these pilot observations, we strongly encourage a larger population study to verify whether mother vaginal microbiome diversity and composition are linked to the prevalence of T1D in children.}, }
@article {pmid30697198, year = {2018}, author = {Naradasu, D and Miran, W and Sakamoto, M and Okamoto, A}, title = {Isolation and Characterization of Human Gut Bacteria Capable of Extracellular Electron Transport by Electrochemical Techniques.}, journal = {Frontiers in microbiology}, volume = {9}, number = {}, pages = {3267}, pmid = {30697198}, issn = {1664-302X}, abstract = {Microorganisms are known to exhibit extracellular electron transfer (EET) in a wide variety of habitats. However, as for the human microbiome which significantly impacts our health, the role and importance of EET has not been widely investigated. In this study, we enriched and isolated the EET-capable bacteria from human gut microbes using an electrochemical enrichment method and examined whether the isolates couple EET with anaerobic respiration or fermentation. Upon the use of energy-rich or minimum media (with acetate or lactate) for electrochemical enrichment with the human gut sample at an electrode potential of +0.4 V [vs. the standard hydrogen electrode (SHE)], both culture conditions showed significant current production. However, EET-capable pure strains were enriched specifically with minimum media, and subsequent incubation using the δ-MnO2-agar plate with lactate or acetate led to the isolation of two EET-capable microbial strains, Gut-S1 and Gut-S2, having 99% of 16S rRNA gene sequence identity with Enterococcus avium (E. avium) and Klebsiella pneumoniae (K. pneumoniae), respectively. While the enrichment involved anaerobic respiration with acetate and lactate, further electrochemistry with E. avium and K. pneumoniae revealed that the glucose fermentation was also coupled with EET. These results indicate that EET couples not only with anaerobic respiration as found in environmental bacteria, but also with fermentation in the human gut.}, }
@article {pmid30692672, year = {2019}, author = {Devoto, AE and Santini, JM and Olm, MR and Anantharaman, K and Munk, P and Tung, J and Archie, EA and Turnbaugh, PJ and Seed, KD and Blekhman, R and Aarestrup, FM and Thomas, BC and Banfield, JF}, title = {Megaphages infect Prevotella and variants are widespread in gut microbiomes.}, journal = {Nature microbiology}, volume = {4}, number = {4}, pages = {693-700}, pmid = {30692672}, issn = {2058-5276}, support = {R01 AI092531/AI/NIAID NIH HHS/United States ; R21 AG055777/AG/NIA NIH HHS/United States ; }, mesh = {Adult ; Animals ; Bacteria/*virology ; Bacteriophages/classification/genetics/*isolation &amp; purification ; Female ; *Gastrointestinal Microbiome ; Genome, Viral ; Humans ; Male ; Metagenome ; *Microbiota ; Middle Aged ; Papio/*microbiology ; Phylogeny ; Prevotella/classification/genetics/*virology ; Swine/*microbiology ; }, abstract = {Bacteriophages (phages) dramatically shape microbial community composition, redistribute nutrients via host lysis and drive evolution through horizontal gene transfer. Despite their importance, much remains to be learned about phages in the human microbiome. We investigated the gut microbiomes of humans from Bangladesh and Tanzania, two African baboon social groups and Danish pigs; many of these microbiomes contain phages belonging to a clade with genomes >540 kilobases in length, the largest yet reported in the human microbiome and close to the maximum size ever reported for phages. We refer to these as Lak phages. CRISPR spacer targeting indicates that Lak phages infect bacteria of the genus Prevotella. We manually curated to completion 15 distinct Lak phage genomes recovered from metagenomes. The genomes display several interesting features, including use of an alternative genetic code, large intergenic regions that are highly expressed and up to 35 putative transfer RNAs, some of which contain enigmatic introns. Different individuals have distinct phage genotypes, and shifts in variant frequencies over consecutive sampling days reflect changes in the relative abundance of phage subpopulations. Recent homologous recombination has resulted in extensive genome admixture of nine baboon Lak phage populations. We infer that Lak phages are widespread in gut communities that contain the Prevotella species, and conclude that megaphages, with fascinating and underexplored biology, may be common but largely overlooked components of human and animal gut microbiomes.}, }
@article {pmid30687300, year = {2018}, author = {Woods, DF and Kozak, IM and Flynn, S and O'Gara, F}, title = {The Microbiome of an Active Meat Curing Brine.}, journal = {Frontiers in microbiology}, volume = {9}, number = {}, pages = {3346}, pmid = {30687300}, issn = {1664-302X}, abstract = {Traditional food products are important to our culture and heritage, and to the continued success of the food industry. Many of the production processes associated with these products have not been subjected to an in-depth microbial compositional analysis. The traditional process of curing meat, both preserves a natural protein source, as well as increasing its organoleptic qualities. One of the most important salting processes is known as Wiltshire curing. The Wiltshire process involves injecting pork with a curing solution and immersing the meat into microbial-rich brine which promotes the development of the distinct organoleptic characteristics. The important microbial component of Wiltshire brine has not been extensively characterized. We analyzed the key microbial component of Wiltshire brine by performing microbiome analysis using Next Generation Sequencing (NGS) technologies. This analysis identified the genera, Marinilactibacillus, Carnobacterium, Leuconostoc, and Vibrio as the core microflora present in Wiltshire curing brine. The important food industrial applications of these bacteria were also assessed. The bacterial diversity of the brine was investigated, and the community composition of the brine was demonstrated to change over time. New knowledge on the characterization of key microbiota associated with a productive Wiltshire brine is an important development linked to promoting enhanced quality and safety of meat processing in the food industry.}, }
@article {pmid30687254, year = {2018}, author = {Forbes, JD and Bernstein, CN and Tremlett, H and Van Domselaar, G and Knox, NC}, title = {A Fungal World: Could the Gut Mycobiome Be Involved in Neurological Disease?.}, journal = {Frontiers in microbiology}, volume = {9}, number = {}, pages = {3249}, pmid = {30687254}, issn = {1664-302X}, abstract = {The human microbiome has received decades of attention from scientific and medical research communities. The human gastrointestinal tract is host to immense populations of microorganisms including bacteria, viruses, archaea, and fungi (the gut microbiota). High-throughput sequencing and computational advancements provide unprecedented ability to investigate the structure and function of microbial communities associated with the human body in health and disease. Most research to date has largely focused on elucidating the bacterial component of the human gut microbiota. Study of the gut "mycobiota," which refers to the diverse array of fungal species, is a relatively new and rapidly progressing field. Though omnipresent, the number and abundance of fungi occupying the human gut is orders of magnitude smaller than that of bacteria. Recent insights however, have suggested that the gut mycobiota may be intricately linked to health and disease. Evaluation of the gut mycobiota has shown that not only are the fungal communities altered in disease, but they also play a role in maintaining intestinal homeostasis and influencing systemic immunity. In addition, it is now widely accepted that host-fungi and bacteria-fungi associations are critical to host health. While research of the gut mycobiota in health and disease is on the rise, little research has been performed in the context of neuroimmune and neurodegenerative conditions. Gut microbiota dysbiosis (specifically bacteria and archaea) have been reported in neurological diseases such as multiple sclerosis, amyotrophic lateral sclerosis, and Alzheimer's, among others. Given the widely accepted bacteria-fungi associations and paucity of mycobiota-specific studies in neurological disease, this review discusses the potential role fungi may play in multiple sclerosis and other neurological diseases. Herein, we provide an overview of recent advances in gut mycobiome research and discuss the plausible role of both intestinal and non-intestinal fungi in the context of neuroimmune and neurodegenerative conditions.}, }
@article {pmid30675064, year = {2019}, author = {Tanoue, T and Morita, S and Plichta, DR and Skelly, AN and Suda, W and Sugiura, Y and Narushima, S and Vlamakis, H and Motoo, I and Sugita, K and Shiota, A and Takeshita, K and Yasuma-Mitobe, K and Riethmacher, D and Kaisho, T and Norman, JM and Mucida, D and Suematsu, M and Yaguchi, T and Bucci, V and Inoue, T and Kawakami, Y and Olle, B and Roberts, B and Hattori, M and Xavier, RJ and Atarashi, K and Honda, K}, title = {A defined commensal consortium elicits CD8 T cells and anti-cancer immunity.}, journal = {Nature}, volume = {565}, number = {7741}, pages = {600-605}, doi = {10.1038/s41586-019-0878-z}, pmid = {30675064}, issn = {1476-4687}, support = {DK43351/NH/NIH HHS/United States ; AT009708/NH/NIH HHS/United States ; }, mesh = {Adenocarcinoma/*immunology/pathology/*therapy ; Animals ; Antigens, CD/metabolism ; Bacteria/*classification/immunology/isolation &amp; purification ; CD8-Positive T-Lymphocytes/cytology/*immunology ; Cell Line, Tumor ; Dendritic Cells/immunology ; Feces/microbiology ; Female ; Gastrointestinal Microbiome/*immunology ; Healthy Volunteers ; Histocompatibility Antigens Class I/immunology ; Humans ; Integrin alpha Chains/metabolism ; Interferon-gamma/biosynthesis/immunology ; Listeria monocytogenes/immunology ; Listeriosis/immunology/microbiology/*prevention &amp; control ; Male ; Mice ; Programmed Cell Death 1 Receptor/antagonists &amp; inhibitors/immunology ; Symbiosis/*immunology ; Xenograft Model Antitumor Assays ; }, abstract = {There is a growing appreciation for the importance of the gut microbiota as a therapeutic target in various diseases. However, there are only a handful of known commensal strains that can potentially be used to manipulate host physiological functions. Here we isolate a consortium of 11 bacterial strains from healthy human donor faeces that is capable of robustly inducing interferon-γ-producing CD8 T cells in the intestine. These 11 strains act together to mediate the induction without causing inflammation in a manner that is dependent on CD103[+] dendritic cells and major histocompatibility (MHC) class Ia molecules. Colonization of mice with the 11-strain mixture enhances both host resistance against Listeria monocytogenes infection and the therapeutic efficacy of immune checkpoint inhibitors in syngeneic tumour models. The 11 strains primarily represent rare, low-abundance components of the human microbiome, and thus have great potential as broadly effective biotherapeutics.}, }
@article {pmid30671046, year = {2018}, author = {Zhang, C and Thakkar, PV and Powell, SE and Sharma, P and Vennelaganti, S and Betel, D and Shah, MA}, title = {A Comparison of Homogenization vs. Enzymatic Lysis for Microbiome Profiling in Clinical Endoscopic Biopsy Tissue Samples.}, journal = {Frontiers in microbiology}, volume = {9}, number = {}, pages = {3246}, pmid = {30671046}, issn = {1664-302X}, abstract = {Identification of the human microbiome has proven to be of utmost importance with the emerging role of bacteria in various physiological and pathological processes. High throughput sequencing strategies have evolved to assess the composition of the microbiome. To identify possible bias that may exist in the processing of tissue for whole genome sequencing (WGS), it is important to evaluate the extraction method on the overall microbial content and composition. Here we compare two different methods of extraction, homogenization vs. enzymatic lysis, on gastric, esophageal and colorectal biopsies and survey the microbial content and composition using WGS and quantitative PCR (qPCR). We examined total bacterial content using universal 16S rDNA qPCR as well as the abundance of three phyla (Actinobacter, Firmicutes, Bacteroidetes) and one genus (Fusobacterium). We found minimal differences between the two extraction methods in the overall community structure. Furthermore, based on our qPCR analysis, neither method demonstrated preferential extraction of any particular clade of bacteria, nor significantly altered the detection of Gram-positive or Gram-negative organisms. However, although the overall microbial composition remained very similar and the most prevalent bacteria could be detected effectively using either method, the precise community structure and microbial abundances between the two methods were different, primarily due to variations in detection of low abundance genus. We also demonstrate that the homogenization extraction method provides higher microbial DNA content and higher read counts from human tissue biopsy samples of the gastrointestinal tract.}, }
@article {pmid30670574, year = {2019}, author = {Dominguez-Bello, MG and Godoy-Vitorino, F and Knight, R and Blaser, MJ}, title = {Role of the microbiome in human development.}, journal = {Gut}, volume = {68}, number = {6}, pages = {1108-1114}, pmid = {30670574}, issn = {1468-3288}, mesh = {Biological Evolution ; Female ; Fetal Development/*physiology ; *Health Status ; *Human Development ; Humans ; Infant, Newborn ; Male ; Microbiota/*genetics/physiology ; }, abstract = {The host-microbiome supraorganism appears to have coevolved and the unperturbed microbial component of the dyad renders host health sustainable. This coevolution has likely shaped evolving phenotypes in all life forms on this predominantly microbial planet. The microbiota seems to exert effects on the next generation from gestation, via maternal microbiota and immune responses. The microbiota ecosystems develop, restricted to their epithelial niches by the host immune system, concomitantly with the host chronological development, providing early modulation of physiological host development and functions for nutrition, immunity and resistance to pathogens at all ages. Here, we review the role of the microbiome in human development, including evolutionary considerations, and the maternal/fetal relationships, contributions to nutrition and growth. We also discuss what constitutes a healthy microbiota, how antimicrobial modern practices are impacting the human microbiota, the associations between microbiota perturbations, host responses and diseases rocketing in urban societies and potential for future restoration.}, }
@article {pmid30666529, year = {2019}, author = {Bilen, M and Fonkou, MDM and Caputo, A and Nguyen, TT and Di Pinto, F and Bittar, F and Daoud, Z and Levasseur, A and Fournier, PE and Raoult, D and Cadoret, F}, title = {Phoenicibacter congonensis gen. nov., sp. nov., a new genus isolated from the human gut and its description using a taxonogenomic approach.}, journal = {Antonie van Leeuwenhoek}, volume = {112}, number = {5}, pages = {775-784}, doi = {10.1007/s10482-018-01211-1}, pmid = {30666529}, issn = {1572-9699}, support = {10-IAHU- 03//Agence Nationale de la Recherche/ ; FEDER PRIMI//Conseil R?gional Provence-Alpes-C?te d'Azur/ ; }, mesh = {Actinobacteria/*classification/genetics/*isolation &amp; purification ; Bacterial Typing Techniques ; Base Composition ; DNA, Bacterial/genetics ; Feces ; Female ; Gastrointestinal Microbiome ; Humans ; Middle Aged ; Phylogeny ; RNA, Ribosomal, 16S/genetics ; }, abstract = {Culturomics has recently allowed the isolation and description of previously uncultured bacteria from the human microbiome at different body sites. As part of a project aiming to describe the human gut microbiota by culturomics, Phoenicibacter congonensis strain Marseille-P3241[T] was isolated from the gut of a 45 years old Pygmy female. In the present work, we aim to describe this strain via the taxonogenomics approach. The major phenotypic, genomic and biochemical characteristics of this strain were analysed. Strain Marseille-P3241[T] is an anaerobic, Gram-positive and motile coccobacillus that grows optimally at 37 °C. The genome of strain Marseille-P3241[T] is 1,447,956 bp long with 43.44% GC content and its 16S rRNA gene sequence exhibited 89% sequence similarity with that of Denitrobacterium detoxificans strain NPOH1[T], the phylogenetically closest related species with current standing in nomenclature. After performing a phylogenetic and genomic analysis, we conclude that strain Marseille-P3241[T] (= CCUG 70681[T] = CSUR P3241[T]) represents the type species of a new genus, for which we propose the name Phoenicibacter congonensis gen. nov., sp. nov.}, }
@article {pmid30666248, year = {2018}, author = {Malla, MA and Dubey, A and Kumar, A and Yadav, S and Hashem, A and Abd Allah, EF}, title = {Exploring the Human Microbiome: The Potential Future Role of Next-Generation Sequencing in Disease Diagnosis and Treatment.}, journal = {Frontiers in immunology}, volume = {9}, number = {}, pages = {2868}, pmid = {30666248}, issn = {1664-3224}, mesh = {Communicable Diseases/etiology/*microbiology ; Computational Biology/trends ; Dysbiosis/complications ; Forecasting ; High-Throughput Nucleotide Sequencing/instrumentation/*trends ; Host Microbial Interactions/*genetics ; Host-Pathogen Interactions/*genetics ; Humans ; Metagenomics/*trends ; Microbiota/*physiology ; Nanotechnology/methods ; }, abstract = {The interaction between the human microbiome and immune system has an effect on several human metabolic functions and impacts our well-being. Additionally, the interaction between humans and microbes can also play a key role in determining the wellness or disease status of the human body. Dysbiosis is related to a plethora of diseases, including skin, inflammatory, metabolic, and neurological disorders. A better understanding of the host-microbe interaction is essential for determining the diagnosis and appropriate treatment of these ailments. The significance of the microbiome on host health has led to the emergence of new therapeutic approaches focused on the prescribed manipulation of the host microbiome, either by removing harmful taxa or reinstating missing beneficial taxa and the functional roles they perform. Culturing large numbers of microbial taxa in the laboratory is problematic at best, if not impossible. Consequently, this makes it very difficult to comprehensively catalog the individual members comprising a specific microbiome, as well as understanding how microbial communities function and influence host-pathogen interactions. Recent advances in sequencing technologies and computational tools have allowed an increasing number of metagenomic studies to be performed. These studies have provided key insights into the human microbiome and a host of other microbial communities in other environments. In the present review, the role of the microbiome as a therapeutic agent and its significance in human health and disease is discussed. Advances in high-throughput sequencing technologies for surveying host-microbe interactions are also discussed. Additionally, the correlation between the composition of the microbiome and infectious diseases as described in previously reported studies is covered as well. Lastly, recent advances in state-of-the-art bioinformatics software, workflows, and applications for analysing metagenomic data are summarized.}, }
@article {pmid30664484, year = {2019}, author = {Lauwers, L and Bastiaens, H and Remmen, R and Keune, H}, title = {The Integration of Interlinkages Between Nature and Human Health in Primary Health Care: Protocol for a Scoping Review.}, journal = {JMIR research protocols}, volume = {8}, number = {1}, pages = {e12510}, pmid = {30664484}, issn = {1929-0748}, mesh = {Scoping Reviews As Topic ; }, abstract = {BACKGROUND: International overview reports and the majority of scientific publications on interlinkages between nature and human health (NHI) do not seem to focus on the role of the health care sector. Primary health care (PHC) is often the first point of contact people have with the health care system and provides comprehensive, accessible, and community-based care that meets the health needs of individuals throughout their life. PHC is a vital backbone for linking knowledge and practice within the organization of health care. This scoping review aims to focus on the potential role of PHC in relation to NHI.<br><br>OBJECTIVE: The objective of this protocol is to present the method used to scope international overview reports and scientific publications on what is mentioned on the integration of NHI in PHC.<br><br>METHODS: The international overview reports have been screened for keywords relating to PHC. We developed a specific search strategy to scope scientific literature on NHI in relation to PHC. The scientific literature search ran in Web of Science (WOS) and PubMed from inception to May 2017. The scientific publications are screened by 2 independent reviewers, which will result in a list of relevant publications that meet eligibility and inclusion criteria.<br><br>RESULTS: On the basis of a first screen on the title of the first 200 results in both search engines, we decided to restrict to WOS. First insights in the international overview reports and the quantitative overview of the results in WOS give a first impression of a missing link between NHI and PHC. The findings are expected to identify knowledge gaps in the translation of evidence on NHI in PHC practices and the role of PHC regarding the application of that evidence in health care practice.<br><br>CONCLUSIONS: This is, to our knowledge, the first study that seeks to relate existing knowledge on NHI to PHC. The presentation of our method through this protocol allows researchers to build upon and improve our work in future research on the practical implementation of NIH. The findings of the scoping review are expected to guide future scientific research, international policy directives, and PHC workers to fill the gaps in the integration of NHI in PHC.<br><br>DERR1-10.2196/12510.}, }
@article {pmid30664014, year = {2019}, author = {Joris, BR and Gloor, GB}, title = {Unaccounted risk of cardiovascular disease: the role of the microbiome in lipid metabolism.}, journal = {Current opinion in lipidology}, volume = {30}, number = {2}, pages = {125-133}, doi = {10.1097/MOL.0000000000000582}, pmid = {30664014}, issn = {1473-6535}, mesh = {Animals ; Atherosclerosis/genetics/immunology/*microbiology/pathology ; Bile Acids and Salts/immunology/metabolism ; Carnitine/immunology/metabolism ; Choline/immunology/metabolism ; Energy Metabolism/genetics/immunology ; Fatty Acids, Volatile/immunology/*metabolism ; Gastrointestinal Microbiome/genetics/*immunology ; Genomics/methods ; High-Throughput Nucleotide Sequencing/methods ; Humans ; Lipid Metabolism/genetics/*immunology ; Metabolic Syndrome/genetics/immunology/*microbiology/pathology ; Methylamines/immunology/*metabolism/pharmacology ; Phosphatidylcholines/immunology/metabolism ; RNA, Ribosomal, 16S/genetics ; T-Lymphocytes, Helper-Inducer/drug effects/immunology/microbiology ; Triglycerides/immunology/metabolism ; }, abstract = {PURPOSE OF REVIEW: Not all of the risk of cardiovascular disease can be explained by diet and genetics, and the human microbiome, which lies at the interface of these two factors, may help explain some of the unaccounted risk. This review examines some of the well established links between the microbiome and cardiovascular health, and proposes relatively unexplored associations.<br><br>RECENT FINDINGS: Byproducts of microbial metabolism are associated with health and disease: Trimethylamine N oxide is associated with atherosclerosis; whereas short-chain fatty acids are associated with decreased inflammation and increased energy expenditure. More broadly, a large number of association studies have been conducted to explore the connections between bacterial taxa and metabolic syndrome. In contrast, the relationship between the microbiome and triglycerides levels remains poorly understood.<br><br>SUMMARY: We suggest that deeper understanding of the molecular mechanisms that drive linkages between the microbiome and disease can be determined by replacing 16S rRNA gene sequencing with shotgun metagenomic sequencing or other functional approaches. Furthermore, to ensure translatability and reproducibility of research findings, a combination of multiple different complementary '-omic' approaches should be employed.}, }
@article {pmid30661755, year = {2019}, author = {Pasolli, E and Asnicar, F and Manara, S and Zolfo, M and Karcher, N and Armanini, F and Beghini, F and Manghi, P and Tett, A and Ghensi, P and Collado, MC and Rice, BL and DuLong, C and Morgan, XC and Golden, CD and Quince, C and Huttenhower, C and Segata, N}, title = {Extensive Unexplored Human Microbiome Diversity Revealed by Over 150,000 Genomes from Metagenomes Spanning Age, Geography, and Lifestyle.}, journal = {Cell}, volume = {176}, number = {3}, pages = {649-662.e20}, pmid = {30661755}, issn = {1097-4172}, support = {BB/L027801/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; MR/M50161X/1/MRC_/Medical Research Council/United Kingdom ; MR/L015080/1/MRC_/Medical Research Council/United Kingdom ; U54 DE023798/DE/NIDCR NIH HHS/United States ; R01 HG005220/HG/NHGRI NIH HHS/United States ; R24 DK110499/DK/NIDDK NIH HHS/United States ; }, mesh = {Big Data ; Genetic Variation/genetics ; Geography ; Humans ; Life Style ; Metagenome/*genetics ; Metagenomics/*methods ; Microbiota/*genetics ; Phylogeny ; Sequence Analysis, DNA/methods ; }, abstract = {The body-wide human microbiome plays a role in health, but its full diversity remains uncharacterized, particularly outside of the gut and in international populations. We leveraged 9,428 metagenomes to reconstruct 154,723 microbial genomes (45% of high quality) spanning body sites, ages, countries, and lifestyles. We recapitulated 4,930 species-level genome bins (SGBs), 77% without genomes in public repositories (unknown SGBs [uSGBs]). uSGBs are prevalent (in 93% of well-assembled samples), expand underrepresented phyla, and are enriched in non-Westernized populations (40% of the total SGBs). We annotated 2.85 M genes in SGBs, many associated with conditions including infant development (94,000) or Westernization (106,000). SGBs and uSGBs permit deeper microbiome analyses and increase the average mappability of metagenomic reads from 67.76% to 87.51% in the gut (median 94.26%) and 65.14% to 82.34% in the mouth. We thus identify thousands of microbial genomes from yet-to-be-named species, expand the pangenomes of human-associated microbes, and allow better exploitation of metagenomic technologies.}, }
@article {pmid30660785, year = {2019}, author = {Marsh, RL and Smith-Vaughan, HC and Chen, ACH and Marchant, JM and Yerkovich, ST and Gibson, PG and Pizzutto, SJ and Hodge, S and Upham, JW and Chang, AB}, title = {Multiple Respiratory Microbiota Profiles Are Associated With Lower Airway Inflammation in Children With Protracted Bacterial Bronchitis.}, journal = {Chest}, volume = {155}, number = {4}, pages = {778-786}, doi = {10.1016/j.chest.2019.01.002}, pmid = {30660785}, issn = {1931-3543}, mesh = {Bacteria/*isolation &amp; purification ; Bronchitis, Chronic/diagnosis/*microbiology ; Bronchoalveolar Lavage Fluid/*microbiology ; Bronchoscopy ; Child ; Child, Preschool ; Female ; Follow-Up Studies ; Humans ; Infant ; Male ; Microbiota/*physiology ; Neutrophils/pathology ; Prospective Studies ; }, abstract = {BACKGROUND: Effective management of protracted bacterial bronchitis (PBB) is needed to prevent chronic disease (eg, bronchiectasis). Understanding the contributions of ongoing airway infection and inflammation is important to achieving optimal PBB treatments. The aim of this study was to compare BAL microbiota, bacterial biomass, and inflammatory markers in children with PBB and age-matched control patients.<br><br>METHODS: BAL was prospectively collected from 28 children with PBB (median age, 1.7 years; range, 0.6-7.4) and 8 control patients (median age, 1.9 years; range, 0.4-4.7). BAL microbiology was determined using culture, 16S ribosomal RNA gene sequencing and bacterial biomass quantification. BAL inflammatory cells, IL-8, and IL-1&#x3b2; were used to assess lower airway inflammation.<br><br>RESULTS: Bacterial biomass, neutrophil percentage, IL-8, and IL-1&#x3b2; levels were significantly higher in children with PBB compared with control patients. BAL microbiota in children with PBB was significantly different to that of control patients (permutational multivariate analysis of variance P&#xa0;= .001) and clustered into four distinct profiles that were either dominated by a respiratory pathogen or contained a more diverse microbiota including Prevotella species. Alpha diversity was unrelated to bacterial biomass, culture of recognized respiratory pathogens, or inflammatory markers.<br><br>CONCLUSIONS: Neutrophilic inflammation in children with PBB was associated with multiple BAL microbiota profiles. Significant associations between inflammatory markers and bacterial biomass, but not alpha diversity, suggest that inflammation in children with PBB is not driven by single pathogenic species. Understanding the role of the entire respiratory microbiota in PBB pathogenesis may be important to determining whether bacteria other than the recognized pathogens contribute to disease recurrence and progression to bronchiectasis.}, }
@article {pmid30658055, year = {2019}, author = {Pellock, SJ and Walton, WG and Ervin, SM and Torres-Rivera, D and Creekmore, BC and Bergan, G and Dunn, ZD and Li, B and Tripathy, A and Redinbo, MR}, title = {Discovery and Characterization of FMN-Binding β-Glucuronidases in the Human Gut Microbiome.}, journal = {Journal of molecular biology}, volume = {431}, number = {5}, pages = {970-980}, pmid = {30658055}, issn = {1089-8638}, support = {P30 ES010126/ES/NIEHS NIH HHS/United States ; T32 GM008570/GM/NIGMS NIH HHS/United States ; R01 CA161879/CA/NCI NIH HHS/United States ; R01 CA207416/CA/NCI NIH HHS/United States ; R01 CA098468/CA/NCI NIH HHS/United States ; }, mesh = {Catalytic Domain/physiology ; Clostridiales/metabolism ; Flavin Mononucleotide/*metabolism ; Gastrointestinal Microbiome/*physiology ; Glucuronidase/*metabolism ; Humans ; Kinetics ; Metagenome/physiology ; Microbiota/physiology ; Ruminococcus/metabolism ; }, abstract = {The human gut microbiota encodes β-glucuronidases (GUSs) that play key roles in health and disease via the metabolism of glucuronate-containing carbohydrates and drugs. Hundreds of putative bacterial GUS enzymes have been identified by metagenomic analysis of the human gut microbiome, but less than 10% have characterized structures and functions. Here we describe a set of unique gut microbial GUS enzymes that bind flavin mononucleotide (FMN). First, we show using mass spectrometry, isothermal titration calorimetry, and x-ray crystallography that a purified GUS from the gut commensal microbe Faecalibacterium prausnitzii binds to FMN on a surface groove located 30 Å away from the active site. Second, utilizing structural and functional data from this FMN-binding GUS, we analyzed the 279 unique GUS sequences from the Human Microbiome Project database and identified 14 putative FMN-binding GUSs. We characterized four of these hits and solved the structure of two, the GUSs from Ruminococcus gnavus and Roseburia hominis, which confirmed that these are FMN binders. Third, binding and kinetic analysis of the FMN-binding site mutants of these five GUSs show that they utilize a conserved site to bind FMN that is not essential for GUS activity, but can affect KM. Lastly, a comprehensive structural review of the PDB reveals that the FMN-binding site employed by these enzymes is unlike any structurally characterized FMN binders to date. These findings reveal the first instance of an FMN-binding glycoside hydrolase and suggest a potential link between FMN and carbohydrate metabolism in the human gut microbiota.}, }
@article {pmid30657195, year = {2019}, author = {Espin-Garcia, O and Croitoru, K and Xu, W}, title = {A finite mixture model for X-chromosome association with an emphasis on microbiome data analysis.}, journal = {Genetic epidemiology}, volume = {43}, number = {4}, pages = {427-439}, doi = {10.1002/gepi.22190}, pmid = {30657195}, issn = {1098-2272}, support = {145546//CIHR/Canada ; GET-101831//CIHR/Canada ; CMF108031//CIHR/Canada ; }, mesh = {*Chromosomes, Human, X/genetics ; Cohort Studies ; Crohn Disease/epidemiology/genetics/microbiology ; Data Analysis ; Family ; Female ; Finite Element Analysis ; Gene-Environment Interaction ; Genetic Association Studies/statistics &amp; numerical data ; Genotype ; Heterozygote ; High-Throughput Nucleotide Sequencing ; Humans ; Male ; Microbiota/*genetics ; Models, Genetic ; X Chromosome Inactivation ; }, abstract = {Analysis of the X chromosome has been largely neglected in genetic studies mainly because of complex underlying biological mechanisms. On the other hand, the study of human microbiome data (typically over-dispersed counts with an excess of zeros) has generated great interest recently because of advancements in next-generation sequencing technologies. We propose a novel approach to infer the association between host genetic variants in the X-chromosome and microbiome data. The method accounts for random X-chromosome inactivation (XCI), skewed (or nonrandom) XCI (XCI-S), and escape of XCI (XCI-E). The inference is performed through a finite mixture model (FMM), in which an indicator variable denoting the "true" biological mechanism is treated as missing data. An expectation-maximization algorithm on zero-inflated and two-part models is implemented to estimate genetic effects. We investigate the performance of the FMM along with strategies that assume XCI and XCI-E mechanisms for all subjects compared with alternative approaches. Briefly, an XCI mechanism codes males' genotypes as homozygous females, whereas under XCI-E, males are treated as heterozygous females. By comprehensive simulations, we evaluate tests of the hypothesis under a computationally efficient score statistic. In summary, the FMM renders reduced bias and commensurate power compared to XCI, XCI-E, and alternative strategies while maintaining adequate Type 1 error control. The proposed method has far-reaching applications. In particular, we illustrate its usage on a large-scale human microbiome study, the Genetic, Environmental and Microbial (GEM) project, to test for the genetic association on the X chromosome.}, }
@article {pmid30650377, year = {2019}, author = {Britton, GJ and Contijoch, EJ and Mogno, I and Vennaro, OH and Llewellyn, SR and Ng, R and Li, Z and Mortha, A and Merad, M and Das, A and Gevers, D and McGovern, DPB and Singh, N and Braun, J and Jacobs, JP and Clemente, JC and Grinspan, A and Sands, BE and Colombel, JF and Dubinsky, MC and Faith, JJ}, title = {Microbiotas from Humans with Inflammatory Bowel Disease Alter the Balance of Gut Th17 and RORγt[+] Regulatory T Cells and Exacerbate Colitis in Mice.}, journal = {Immunity}, volume = {50}, number = {1}, pages = {212-224.e4}, pmid = {30650377}, issn = {1097-4180}, support = {P30 CA016087/CA/NCI NIH HHS/United States ; T32 DK007180/DK/NIDDK NIH HHS/United States ; R01 CA190400/CA/NCI NIH HHS/United States ; F30 DK108487/DK/NIDDK NIH HHS/United States ; UL1 TR000124/TR/NCATS NIH HHS/United States ; P30 CA016042/CA/NCI NIH HHS/United States ; R01 GM108505/GM/NIGMS NIH HHS/United States ; F31 DK112679/DK/NIDDK NIH HHS/United States ; UL1 TR001881/TR/NCATS NIH HHS/United States ; U24 AI118644/AI/NIAID NIH HHS/United States ; P30 DK041301/DK/NIDDK NIH HHS/United States ; R01 DK085691/DK/NIDDK NIH HHS/United States ; P01 DK046763/DK/NIDDK NIH HHS/United States ; P50 AT008661/AT/NCCIH NIH HHS/United States ; }, mesh = {Animals ; Cell Differentiation ; Colitis/chemically induced/immunology/*microbiology ; Disease Models, Animal ; Disease Progression ; Gastrointestinal Microbiome/*genetics ; Homeostasis ; Humans ; Inflammatory Bowel Diseases/*immunology/*microbiology ; Mice ; Mice, Inbred C57BL ; Nuclear Receptor Subfamily 1, Group F, Member 3/metabolism ; RNA, Ribosomal, 16S/*genetics ; T-Lymphocytes, Regulatory/*immunology ; Th17 Cells/*metabolism ; }, abstract = {Microbiota are thought to influence the development and progression of inflammatory bowel disease (IBD), but determining generalizable effects of microbiota on IBD etiology requires larger-scale functional analyses. We colonized germ-free mice with intestinal microbiotas from 30 healthy and IBD donors and determined the homeostatic intestinal T cell response to each microbiota. Compared to microbiotas from healthy donors, transfer of IBD microbiotas into germ-free mice increased numbers of intestinal Th17 cells and Th2 cells and decreased numbers of RORγt[+] Treg cells. Colonization with IBD microbiotas exacerbated disease in a model where colitis is induced upon transfer of naive T cells into Rag1[-/-] mice. The proportions of Th17 and RORγt[+] Treg cells induced by each microbiota were predictive of human disease status and accounted for disease severity in the Rag1[-/-] colitis model. Thus, an impact on intestinal Th17 and RORγt[+] Treg cell compartments emerges as a unifying feature of IBD microbiotas, suggesting a general mechanism for microbial contribution to IBD pathogenesis.}, }
@article {pmid30649168, year = {2019}, author = {Griffith, JC and Morgan, XC}, title = {Invited Commentary: Improving the Accessibility of Human Microbiome Project Data Through Integration With R/Bioconductor.}, journal = {American journal of epidemiology}, volume = {188}, number = {6}, pages = {1027-1030}, doi = {10.1093/aje/kwz007}, pmid = {30649168}, issn = {1476-6256}, mesh = {Computational Biology ; Humans ; Metagenome ; *Microbiota ; Phylogeny ; RNA, Ribosomal, 16S ; }, abstract = {Alterations in the composition of the microbiota have been implicated in many diseases. The Human Microbiome Project (HMP) provides a comprehensive reference data set of the "normal" human microbiome of 242 healthy adults at 5 major body sites. The HMP used both 16S ribosomal RNA gene sequencing and whole-genome metagenomic sequencing to profile the subjects' microbial communities. However, accessing and analyzing the HMP data set still presents technical and bioinformatic challenges, given that researchers must import the microbiome data, integrate phylogenetic trees, and access and merge public and restricted metadata. The HMP16SData R/Bioconductor package developed by Schiffer et al. (Am J Epidemiol. 2019;188(6):1023-1026) greatly simplifies access to the HMP data by combining 16S taxonomic abundance data, public patient metadata, and phylogenetic trees as a single data object. The authors also provide an interface for users with approved Database of Genotypes and Phenotypes (dbGaP) projects to easily retrieve and merge the controlled-access HMP metadata. This package has a broad range of appeal to researchers across disciplines and with various levels of expertise in using R and/or other statistical tools, which translates to improved data accessibility for public health research, with data from healthy individuals serving as a reference for disease-associated studies.}, }
@article {pmid30649166, year = {2019}, author = {Schiffer, L and Azhar, R and Shepherd, L and Ramos, M and Geistlinger, L and Huttenhower, C and Dowd, JB and Segata, N and Waldron, L}, title = {HMP16SData: Efficient Access to the Human Microbiome Project Through Bioconductor.}, journal = {American journal of epidemiology}, volume = {188}, number = {6}, pages = {1023-1026}, pmid = {30649166}, issn = {1476-6256}, support = {R01 HG005220/HG/NHGRI NIH HHS/United States ; R21 AI121784/AI/NIAID NIH HHS/United States ; U24 CA180996/CA/NCI NIH HHS/United States ; U54 DE023798/DE/NIDCR NIH HHS/United States ; }, mesh = {Adolescent ; Adult ; Computational Biology ; Databases, Genetic/*statistics &amp; numerical data ; Female ; Humans ; Male ; Microbiota/*physiology ; RNA, Ribosomal, 16S/*metabolism ; Young Adult ; }, abstract = {Phase 1 of the Human Microbiome Project (HMP) investigated 18 body subsites of 242 healthy American adults to produce the first comprehensive reference for the composition and variation of the "healthy" human microbiome. Publicly available data sets from amplicon sequencing of two 16S ribosomal RNA variable regions, with extensive controlled-access participant data, provide a reference for ongoing microbiome studies. However, utilization of these data sets can be hindered by the complex bioinformatic steps required to access, import, decrypt, and merge the various components in formats suitable for ecological and statistical analysis. The HMP16SData package provides count data for both 16S ribosomal RNA variable regions, integrated with phylogeny, taxonomy, public participant data, and controlled participant data for authorized researchers, using standard integrative Bioconductor data objects. By removing bioinformatic hurdles of data access and management, HMP16SData enables epidemiologists with only basic R skills to quickly analyze HMP data.}, }
@article {pmid30644740, year = {2019}, author = {Brasili, E and Hassimotto, NMA and Del Chierico, F and Marini, F and Quagliariello, A and Sciubba, F and Miccheli, A and Putignani, L and Lajolo, F}, title = {Daily Consumption of Orange Juice from Citrus sinensis L. Osbeck cv. Cara Cara and cv. Bahia Differently Affects Gut Microbiota Profiling as Unveiled by an Integrated Meta-Omics Approach.}, journal = {Journal of agricultural and food chemistry}, volume = {67}, number = {5}, pages = {1381-1391}, doi = {10.1021/acs.jafc.8b05408}, pmid = {30644740}, issn = {1520-5118}, mesh = {Adult ; Bacteria/classification/genetics/isolation &amp; purification ; Brazil ; Citrus sinensis/chemistry/classification/*metabolism ; Female ; Fruit/chemistry/classification ; Fruit and Vegetable Juices/*analysis ; *Gastrointestinal Microbiome ; Gastrointestinal Tract/metabolism/microbiology ; Humans ; Male ; Middle Aged ; Young Adult ; }, abstract = {We have investigated the effect of intake of two different orange juices from Citrus sinensis cv. "Cara Cara" and cv. "Bahia" on faecal microbiota and metabolome using an integrated meta-omics approach. Following a randomized crossover design, healthy subjects daily consumed 500 mL of orange juice from Cara Cara or Bahia juices or an isocaloric control drink. Stools were collected at baseline (T0) and after a week (T7) of intervention. Operational taxonomic units (OTUs) were pyrosequenced targeting 16S rRNA, and faecal metabolites were analyzed by an untargeted metabolomics approach based on [1]H NMR spectroscopy. The major shift observed in microbiota composition after orange juice intake was the increased abundance of a network of Clostridia OTUs from Mogibacteriaceae, Tissierellaceae, Veillonellaceae, Odoribacteraceae, and Ruminococcaceae families, whose members were differently affected by Cara Cara or Bahia juice consumption. A core of six metabolites such as inositol, choline, lysine, arginine, urocanic acid, and formate significantly increased in Cara Cara compared to the Bahia group.}, }
@article {pmid30643895, year = {2019}, author = {Gutiérrez-Barranquero, JA and Parages, ML and Dobson, ADW and Reen, FJ and O'Gara, F}, title = {Genome Sequence of Paracoccus sp. JM45, a Bacterial Strain Isolated from a Marine Sponge with a Dual Quorum Sensing Inhibition Activity.}, journal = {Microbiology resource announcements}, volume = {8}, number = {2}, pages = {}, pmid = {30643895}, issn = {2576-098X}, abstract = {The draft genome sequence of Paracoccus sp. strain JM45, isolated from a marine sponge harvested off the west coast of Ireland, is reported here. Quorum sensing and quorum sensing inhibition activities have been reported recently for this bacterium, and genomic analysis supports its potential use for novel therapeutic development.}, }
@article {pmid30635376, year = {2019}, author = {Feng, S and McLellan, SL}, title = {Highly Specific Sewage-Derived Bacteroides Quantitative PCR Assays Target Sewage-Polluted Waters.}, journal = {Applied and environmental microbiology}, volume = {85}, number = {6}, pages = {}, pmid = {30635376}, issn = {1098-5336}, support = {R01 AI091829/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Bacteroides/classification/genetics/*isolation &amp; purification ; DNA, Bacterial/genetics ; Feces/microbiology ; Fresh Water/*microbiology ; Humans ; RNA, Ribosomal, 16S/genetics ; Real-Time Polymerase Chain Reaction/*methods ; Sensitivity and Specificity ; Sewage/*microbiology ; Water Pollution/analysis ; }, abstract = {The identification of sewage contamination in water has primarily relied on the detection of human-associated Bacteroides using markers within the V2 region of the 16S rRNA gene. Despite the establishment of multiple assays that target the HF183 cluster (i.e., Bacteroides dorei) and other Bacteroides organisms (e.g., Bacteroides thetaiotaomicron), the potential for more human-associated markers in this genus has not been explored in depth. We examined the Bacteroides population structure in sewage and animal hosts across the V4V5 and V6 hypervariable regions. Using near-full-length cloned sequences, we identified the sequences in the V4V5 and V6 hypervariable regions that are linked to the HF183 marker in the V2 region and found these sequences were present in multiple animals. In addition, the V4V5 and V6 regions contained human fecal marker sequences for organisms that were independent of the HF183 cluster. The most abundant Bacteroides in untreated sewage was not human associated but pipe derived. Two TaqMan quantitative PCR (qPCR) assays targeting the V4V5 and V6 regions of this organism were developed. Validation studies using fecal samples from seven animal hosts (n = 76) and uncontaminated water samples (n = 30) demonstrated the high specificity of the assays for sewage. Freshwater Bacteroides were also identified in uncontaminated water samples, demonstrating that measures of total Bacteroides do not reflect fecal pollution. A comparison of two previously described human Bacteroides assays (HB and HF183/BacR287) in municipal wastewater influent and sewage-contaminated urban water samples revealed identical results, illustrating the assays target the same organism. The detection of sewage-derived Bacteroides provided an independent measure of sewage-impacted waters.IMPORTANCEBacteroides are major members of the gut microbiota, and host-specific organisms within this genus have been used extensively to gain information on pollution sources. This study provides a broad view of the population structure of Bacteroides within sewage to contextualize the well-studied HF183 marker for a human-associated Bacteroides The study also delineates host-specific sequence patterns across multiple hypervariable regions of the 16S rRNA gene to improve our ability to use sequence data to assess water quality. Here, we demonstrate that regions downstream of the HF183 marker are nonspecific but other potential human-associated markers are present. Furthermore, we show the most abundant Bacteroides in sewage is free living, rather than host associated, and specifically found in sewage. Quantitative PCR assays that target organisms specific to sewer pipes offer measures that are independent of the human microbiome for identifying sewage pollution in water.}, }
@article {pmid30626617, year = {2019}, author = {Rowan-Nash, AD and Korry, BJ and Mylonakis, E and Belenky, P}, title = {Cross-Domain and Viral Interactions in the Microbiome.}, journal = {Microbiology and molecular biology reviews : MMBR}, volume = {83}, number = {1}, pages = {}, pmid = {30626617}, issn = {1098-5557}, support = {P20 GM109035/GM/NIGMS NIH HHS/United States ; P20 GM121344/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Archaea/metabolism/pathogenicity ; Bacteria/metabolism/pathogenicity ; Fungi/metabolism/pathogenicity ; Gastrointestinal Microbiome/*physiology ; *Gastrointestinal Tract/microbiology/parasitology/virology ; Helminths/metabolism/pathogenicity ; Host-Parasite Interactions/*physiology ; Humans ; Models, Animal ; Specific Pathogen-Free Organisms ; *Viruses/metabolism/pathogenicity ; }, abstract = {The importance of the microbiome to human health is increasingly recognized and has become a major focus of recent research. However, much of the work has focused on a few aspects, particularly the bacterial component of the microbiome, most frequently in the gastrointestinal tract. Yet humans and other animals can be colonized by a wide array of organisms spanning all domains of life, including bacteria and archaea, unicellular eukaryotes such as fungi, multicellular eukaryotes such as helminths, and viruses. As they share the same host niches, they can compete with, synergize with, and antagonize each other, with potential impacts on their host. Here, we discuss these major groups making up the human microbiome, with a focus on how they interact with each other and their multicellular host.}, }
@article {pmid30619299, year = {2018}, author = {Satitsuksanoa, P and Jansen, K and Głobińska, A and van de Veen, W and Akdis, M}, title = {Regulatory Immune Mechanisms in Tolerance to Food Allergy.}, journal = {Frontiers in immunology}, volume = {9}, number = {}, pages = {2939}, pmid = {30619299}, issn = {1664-3224}, mesh = {Animals ; Cytokines/immunology/metabolism ; Dendritic Cells/immunology ; Dietary Proteins/*immunology/metabolism ; Epithelial Cells/immunology ; Food Hypersensitivity/*immunology ; Gastrointestinal Microbiome/immunology ; Humans ; Immune Tolerance/*immunology ; T-Lymphocytes, Regulatory/*immunology/metabolism ; }, abstract = {Oral tolerance can develop after frequent exposure to food allergens. Upon ingestion, food is digested into small protein fragments in the gastrointestinal tract. Small food particles are later absorbed into the human body. Interestingly, some of these ingested food proteins can cause allergic immune responses, which can lead to food allergy. So far it has not been completely elucidated how these proteins become immunogenic and cause food allergies. In contrast, oral tolerance helps to prevent the pathologic reactions against different types of food antigens from animal or plant origin. Tolerance to food is mainly acquired by dendritic cells, epithelial cells in the gut, and the gut microbiome. A subset of CD103[+] DCs is capable of inducing T regulatory cells (Treg cells) that express anti-inflammatory cytokines. Anergic T cells also contribute to oral tolerance, by reducing the number of effector cells. Similar to Treg cells, B regulatory cells (Breg cells) suppress effector T cells and contribute to the immune tolerance to food allergens. Furthermore, the human microbiome is an essential mediator in the induction of oral tolerance or food allergy. In this review, we outline the current understanding of regulatory immune mechanisms in oral tolerance. The biological changes reflecting early consequences of immune stimulation with food allergens should provide useful information for the development of novel therapeutic treatments.}, }
@article {pmid30619188, year = {2018}, author = {Xiao, J and Chen, L and Yu, Y and Zhang, X and Chen, J}, title = {A Phylogeny-Regularized Sparse Regression Model for Predictive Modeling of Microbial Community Data.}, journal = {Frontiers in microbiology}, volume = {9}, number = {}, pages = {3112}, pmid = {30619188}, issn = {1664-302X}, support = {U01 FD005875/FD/FDA HHS/United States ; }, abstract = {Fueled by technological advancement, there has been a surge of human microbiome studies surveying the microbial communities associated with the human body and their links with health and disease. As a complement to the human genome, the human microbiome holds great potential for precision medicine. Efficient predictive models based on microbiome data could be potentially used in various clinical applications such as disease diagnosis, patient stratification and drug response prediction. One important characteristic of the microbial community data is the phylogenetic tree that relates all the microbial taxa based on their evolutionary history. The phylogenetic tree is an informative prior for more efficient prediction since the microbial community changes are usually not randomly distributed on the tree but tend to occur in clades at varying phylogenetic depths (clustered signal). Although community-wide changes are possible for some conditions, it is also likely that the community changes are only associated with a small subset of "marker" taxa (sparse signal). Unfortunately, predictive models of microbial community data taking into account both the sparsity and the tree structure remain under-developed. In this paper, we propose a predictive framework to exploit sparse and clustered microbiome signals using a phylogeny-regularized sparse regression model. Our approach is motivated by evolutionary theory, where a natural correlation structure among microbial taxa exists according to the phylogenetic relationship. A novel phylogeny-based smoothness penalty is proposed to smooth the coefficients of the microbial taxa with respect to the phylogenetic tree. Using simulated and real datasets, we show that our method achieves better prediction performance than competing sparse regression methods for sparse and clustered microbiome signals.}, }
@article {pmid30604388, year = {2019}, author = {Osman, AEG and Luke, JJ}, title = {The Impact of the Fecal Microbiome on Cancer Immunotherapy.}, journal = {BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy}, volume = {33}, number = {1}, pages = {1-7}, doi = {10.1007/s40259-018-0328-8}, pmid = {30604388}, issn = {1179-190X}, support = {W81XWH-17-1-0265//U.S. Department of Defense/ ; }, mesh = {Gastrointestinal Microbiome/*immunology ; Graft vs Host Disease ; Humans ; Immunotherapy/methods ; Neoplasms/*microbiology/*therapy ; }, abstract = {Recent advances in culture-free methods of studying the human microbiome, coupled with strong bioinformatics tools, have provided new insights on the role of the human microbiome in health and disease. The human gut, in particular, houses a vast number and diverse variety of microbes. A plethora of evidence has demonstrated the significant effects of the gut microbiome on local and systemic immunity. Studies in hematopoietic stem cell transplantation recipients provided early evidence of the involvement of the gut microbiome in the development of graft-versus-host disease and its related mortality. Cancer immunotherapy and checkpoint inhibitors, in particular, harness the power of the host's immune system to fight a range of malignancies. Resistance to immunotherapy and fatal immune-related adverse events both continue to be challenges in the field. The role of the human gut microbiome in affecting the response to immunotherapy was recently uncovered through a series of preclinical and clinical studies. The evidence presented in these studies provides tremendous potential for gut microbes to be used for biomarker development and therapeutic intervention trials.}, }
@article {pmid32422014, year = {2019}, author = {Lambring, CB and Siraj, S and Patel, K and Sankpal, UT and Mathew, S and Basha, R}, title = {Impact of the Microbiome on the Immune System.}, journal = {Critical reviews in immunology}, volume = {39}, number = {5}, pages = {313-328}, pmid = {32422014}, issn = {1040-8401}, support = {P20 CA233355/CA/NCI NIH HHS/United States ; R25 HL125447/HL/NHLBI NIH HHS/United States ; S21 MD012472/MD/NIMHD NIH HHS/United States ; U54 MD006882/MD/NIMHD NIH HHS/United States ; }, mesh = {Animals ; Autoimmune Diseases/*immunology/microbiology ; Host-Pathogen Interactions ; Humans ; Immune System/immunology/*microbiology ; Immunity ; Infections/*immunology/microbiology ; Metabolic Diseases/*immunology/microbiology ; Microbiota/immunology ; Neoplasms/*immunology/microbiology ; }, abstract = {Higher organisms are all born with general immunity as well as with, increasingly, more specific immune systems. All immune mechanisms function with the intent of aiding the body in defense against infection. Internal and external factors alike have varying effects on the immune system, and the immune response is tailored specifically to each one. Accompanying the components of the human innate and adaptive immune systems are the other intermingling systems of the human body. Increasing understanding of the body's immune interactions with other systems has opened new avenues of study, including that of the microbiome. The microbiome has become a highly active area of research over the last 10 to 20 years since the NIH began funding the Human Microbiome Project (HMP), which was established in 2007. Several publications have focused on the characterization, functions, and complex interplay of the microbiome as it relates to the rest of the body. A dysfunction between the microbiome and the host has been linked to various diseases including cancers, metabolic deficiencies, autoimmune disorders, and infectious diseases. Further understanding of the microbiome and its interaction with the host in relation to diseases is needed in order to understand the implications of microbiome dysfunction and the possible use of microbiota in the prevention of disease. In this review, we have summarized information on the immune system, the microbiome, the microbiome's interplay with other systems, and the association of the immune system and the microbiome in diseases such as diabetes and colorectal cancer.}, }
@article {pmid30588567, year = {2019}, author = {Wei, F and Wu, Q and Hu, Y and Huang, G and Nie, Y and Yan, L}, title = {Conservation metagenomics: a new branch of conservation biology.}, journal = {Science China. Life sciences}, volume = {62}, number = {2}, pages = {168-178}, doi = {10.1007/s11427-018-9423-3}, pmid = {30588567}, issn = {1869-1889}, mesh = {Animals ; Animals, Wild/*microbiology/physiology ; Biological Coevolution ; Conservation of Natural Resources/*trends ; Humans ; *Metagenomics ; Microbiota/genetics/*physiology ; }, abstract = {Multifaceted approaches are required to monitor wildlife populations and improve conservation efforts. In the last decade, increasing evidence suggests that metagenomic analysis offers valuable perspectives and tools for identifying microbial communities and functions. It has become clear that gut microbiome plays a critical role in health, nutrition, and physiology of wildlife, including numerous endangered animals in the wild and in captivity. In this review, we first introduce the human microbiome and metagenomics, highlighting the importance of microbiome for host fitness. Then, for the first time, we propose the concept of conservation metagenomics, an emerging subdiscipline of conservation biology, which aims to understand the roles of the microbiota in evolution and conservation of endangered animals. We define what conservation metagenomics is along with current approaches, main scientific issues and significant implications in the study of host evolution, physiology, nutrition, ecology and conservation. We also discuss future research directions of conservation metagenomics. Although there is still a long way to go, conservation metagenomics has already shown a significant potential for improving the conservation and management of wildlife.}, }
@article {pmid30584647, year = {2019}, author = {Zhang, J and Zhang, F and Zhao, C and Xu, Q and Liang, C and Yang, Y and Wang, H and Shang, Y and Wang, Y and Mu, X and Zhu, D and Zhang, C and Yang, J and Yao, M and Zhang, L}, title = {Dysbiosis of the gut microbiome is associated with thyroid cancer and thyroid nodules and correlated with clinical index of thyroid function.}, journal = {Endocrine}, volume = {64}, number = {3}, pages = {564-574}, pmid = {30584647}, issn = {1559-0100}, support = {31471202//the National Natural Science Foundation of China/International ; 81670822//the National Natural Science Foundation of China/International ; 2016YYSP009//the Shandong Provincial Key Research and Development Program/International ; 2016GNS023//Weihai Technique Extension Project/International ; 17-3-3-10-nsh//Qingdao Key Research Project/International ; tshw20120206//the Taishan Scholars Program of Shandong Province/International ; }, mesh = {Adult ; Dysbiosis/*pathology ; Female ; *Gastrointestinal Microbiome ; Humans ; Male ; Middle Aged ; Thyroid Function Tests ; Thyroid Gland/*pathology/physiopathology ; Thyroid Neoplasms/microbiology/*pathology/physiopathology ; Thyroid Nodule/microbiology/*pathology/physiopathology ; }, abstract = {PURPOSE: Thyroid cancer and thyroid nodules are the most prevalent form of thyroid endocrine disorder. The balance of gut microbiome is highly crucial for a healthy human body, especially for the immune and endocrine system. However, the relationship between gut microbiome and the thyroid endocrine disorders such as thyroid cancer and thyroid nodules has not been reported yet.<br><br>METHODS: A cohort of 74 patients was recruited for this study. Among them, 20 patients had thyroid cancer, 18 patients had thyroid nodules, and 36 were matched healthy controls. Gut microbiome composition was analyzed by 16S rRNA (16S ribosomal RNA) gene-based sequencing protocol.<br><br>RESULTS: We compared the gut microbiome results of 74 subjects and established the correlation between gut microbiome and thyroid endocrine function for both thyroid cancer and thyroid nodules. The results inferred that alpha and beta diversity were different for patients with thyroid tumor than the healthy controls (p&#x2009;<&#x2009;0.01). In comparison to healthy controls, the relative abundance of Neisseria (p&#x2009;<&#x2009;0.001) and Streptococcus (p&#x2009;<&#x2009;0.001) was significantly higher for thyroid cancer and thyroid nodules. Butyricimonas (p&#x2009;<&#x2009;0.001) and Lactobacillus (p&#x2009;<&#x2009;0.001) displayed notably lower relative abundance for thyroid cancer and thyroid nodules, respectively. It was also found that the clinical indexes were correlated with gut microbiome.<br><br>CONCLUSION: Our results indicate that both thyroid cancer and thyroid nodules are associated with the composition of gut microbiome. These results may support further clinical diagnosis to a great extent and help in developing potential probiotics to facilitate the treatment of thyroid cancer and thyroid nodules.}, }
@article {pmid30578461, year = {2019}, author = {Nobili, V and Mosca, A and Alterio, T and Cardile, S and Putignani, L}, title = {Fighting Fatty Liver Diseases with Nutritional Interventions, Probiotics, Symbiotics, and Fecal Microbiota Transplantation (FMT).}, journal = {Advances in experimental medicine and biology}, volume = {1125}, number = {}, pages = {85-100}, doi = {10.1007/5584_2018_318}, pmid = {30578461}, issn = {0065-2598}, mesh = {*Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; Non-alcoholic Fatty Liver Disease/*therapy ; Probiotics/*therapeutic use ; Randomized Controlled Trials as Topic ; }, abstract = {Pediatric obesity is rising worldwide leading the worrying phenomenon of nonalcoholic fatty liver disease (NAFLD) to shift into one of the most frequent causes of chronic liver illness in childhood. Occurrence of NAFLD depends on several factors such as the geographical area and the diagnostic modalities used; overall it ranges between 3% and 10% of pediatric population, increasing up to 70% in patients with metabolic comorbidities (Manco M, Bottazzo G, DeVito R et al, J Am Coll Nutr 27:667-676, 2008).Recent findings have related the intestinal microbiota to a plethora of pathological conditions, including type 2 diabetes (T2D), obesity, and nonalcoholic steatohepatitis (NASH). One of the emerging areas of the study is the link between liver diseases and gut microbiome, which has added new information to the understanding of the so-called gut-liver axis.In order to address the role of gut microbiome in NAFLD onset and progression, it is necessary to "decipher" operational codes for microbiome investigation within the context of advanced laboratory medicine to capture microbiome features and, hence, to address the function of the intestinal microbiome within the gut microbiota-liver axis.Results of these investigations have allowed the beginning of implementing the usage of probiotics and symbiotics in the medical approach of obesity and NAFLD in adults and children. Several randomized clinical trials (RCTs) have been already published on fecal microbiota transplantation (FMT), T2D, NASH, and inflammatory bowel disease (IBD).This review proposes to describe the current state of knowledge on the ways fatty liver diseases can be addressed with nutritional interventions, probiotics, symbiotics, and FMT.}, }
@article {pmid30578265, year = {2019}, author = {Stubbendieck, RM and May, DS and Chevrette, MG and Temkin, MI and Wendt-Pienkowski, E and Cagnazzo, J and Carlson, CM and Gern, JE and Currie, CR}, title = {Competition among Nasal Bacteria Suggests a Role for Siderophore-Mediated Interactions in Shaping the Human Nasal Microbiota.}, journal = {Applied and environmental microbiology}, volume = {85}, number = {10}, pages = {}, pmid = {30578265}, issn = {1098-5336}, support = {P01 HL070831/HL/NHLBI NIH HHS/United States ; T15 LM007359/LM/NLM NIH HHS/United States ; T32 GM008505/GM/NIGMS NIH HHS/United States ; U19 AI109673/AI/NIAID NIH HHS/United States ; }, mesh = {Actinobacteria/*physiology ; Humans ; Microbiota/*physiology ; Nasal Cavity/*microbiology ; Siderophores/*metabolism ; Staphylococcus/*physiology ; }, abstract = {Resources available in the human nasal cavity are limited. Therefore, to successfully colonize the nasal cavity, bacteria must compete for scarce nutrients. Competition may occur directly through interference (e.g., antibiotics) or indirectly by nutrient sequestration. To investigate the nature of nasal bacterial competition, we performed coculture inhibition assays between nasal Actinobacteria and Staphylococcus spp. We found that isolates of coagulase-negative staphylococci (CoNS) were sensitive to growth inhibition by Actinobacteria but that Staphylococcus aureus isolates were resistant to inhibition. Among Actinobacteria, we observed that Corynebacterium spp. were variable in their ability to inhibit CoNS. We sequenced the genomes of 10 Corynebacterium species isolates, including 3 Corynebacterium propinquum isolates that strongly inhibited CoNS and 7 other Corynebacterium species isolates that only weakly inhibited CoNS. Using a comparative genomics approach, we found that the C. propinquum genomes were enriched in genes for iron acquisition and harbored a biosynthetic gene cluster (BGC) for siderophore production, absent in the noninhibitory Corynebacterium species genomes. Using a chrome azurol S assay, we confirmed that C. propinquum produced siderophores. We demonstrated that iron supplementation rescued CoNS from inhibition by C. propinquum, suggesting that inhibition was due to iron restriction through siderophore production. Through comparative metabolomics and molecular networking, we identified the siderophore produced by C. propinquum as dehydroxynocardamine. Finally, we confirmed that the dehydroxynocardamine BGC is expressed in vivo by analyzing human nasal metatranscriptomes from the NIH Human Microbiome Project. Together, our results suggest that bacteria produce siderophores to compete for limited available iron in the nasal cavity and improve their fitness.IMPORTANCE Within the nasal cavity, interference competition through antimicrobial production is prevalent. For instance, nasal Staphylococcus species strains can inhibit the growth of other bacteria through the production of nonribosomal peptides and ribosomally synthesized and posttranslationally modified peptides. In contrast, bacteria engaging in exploitation competition modify the external environment to prevent competitors from growing, usually by hindering access to or depleting essential nutrients. As the nasal cavity is a nutrient-limited environment, we hypothesized that exploitation competition occurs in this system. We determined that Corynebacterium propinquum produces an iron-chelating siderophore, and this iron-sequestering molecule correlates with the ability to inhibit the growth of coagulase-negative staphylococci. Furthermore, we found that the genes required for siderophore production are expressed in vivo Thus, although siderophore production by bacteria is often considered a virulence trait, our work indicates that bacteria may produce siderophores to compete for limited iron in the human nasal cavity.}, }
@article {pmid30577530, year = {2018}, author = {Yang, AJ and Marito, S and Yang, JJ and Keshari, S and Chew, CH and Chen, CC and Huang, CM}, title = {A Microtube Array Membrane (MTAM) Encapsulated Live Fermenting Staphylococcus epidermidis as a Skin Probiotic Patch against Cutibacterium acnes.}, journal = {International journal of molecular sciences}, volume = {20}, number = {1}, pages = {}, pmid = {30577530}, issn = {1422-0067}, support = {106-2320-B-008, 105-2314-B-008-001, 101-2221-E-038-009-, 107-2314-B-008 -001, 107-2622-B-008-002-CC1 and 106/107-2622-B-008-001-CC1//Ministry of Science and Technology, Taiwan/ ; NHRI-EX106-10607SI//NHRI/ ; }, mesh = {Animals ; *Antibiosis ; Chemokine CXCL2/metabolism ; Dermatitis/metabolism/microbiology ; Fermentation ; Glycerol/metabolism ; Humans ; Mice ; *Probiotics ; Propionibacteriaceae/*physiology ; Skin/*microbiology ; Staphylococcus epidermidis/*physiology ; }, abstract = {Antibiotics without selectivity for acne treatment may destroy the beneficial microbes in the human microbiome that helps to fight Cutibacterium acnes (C. acnes), a bacterium associated with inflammatory acne vulgaris. Probiotic treatment by direct application of live Staphylococcus epidermidis (S. epidermidis) onto the open acne lesions may run the risk of bloodstream infections. Here, we fabricated the polysulfone microtube array membranes (PSF MTAM) to encapsulate probiotic S. epidermidis. We demonstrate that the application of the encapsulation of S. epidermidis in PSF MTAM enhanced the glycerol fermentation activities of S. epidermidis. To mimic the granulomatous type of acne inflammatory acne vulgaris, the ears of mice were injected intradermally with C. acnes to induce the secretion of macrophage inflammatory protein-2 (MIP-2), a murine counterpart of human interleukin (IL)-8. The C. acnes-injected mouse ears were covered with a PST MTAM encapsulated with or without S. epidermidis in the presence of glycerol. The application of S. epidermidis-encapsulated PST MTAM plus glycerol onto the C. acnes-injected mouse ears considerably reduced the growth of C. acnes and the production of MIP-2. Furthermore, no S. epidermidis leaked from PSF MTAM into mouse skin. The S. epidermidis-encapsulated PST MTAM functions as a probiotic acne patch.}, }
@article {pmid30575732, year = {2018}, author = {Coryell, M and McAlpine, M and Pinkham, NV and McDermott, TR and Walk, ST}, title = {The gut microbiome is required for full protection against acute arsenic toxicity in mouse models.}, journal = {Nature communications}, volume = {9}, number = {1}, pages = {5424}, pmid = {30575732}, issn = {2041-1723}, support = {F31 ES026884/ES/NIEHS NIH HHS/United States ; R01 CA215784/CA/NCI NIH HHS/United States ; R21 ES026411/ES/NIEHS NIH HHS/United States ; }, mesh = {Adult ; Animals ; Arsenic/metabolism ; Arsenic Poisoning/*prevention &amp; control ; Faecalibacterium prausnitzii/*physiology ; *Fecal Microbiota Transplantation ; Female ; *Gastrointestinal Microbiome ; *Germ-Free Life ; Humans ; Inactivation, Metabolic ; Male ; Methyltransferases/physiology ; Mice, Inbred C57BL ; Mice, Transgenic ; Young Adult ; }, abstract = {Arsenic poisons an estimated 200 million people worldwide through contaminated food and drinking water. Confusingly, the gut microbiome has been suggested to both mitigate and exacerbate arsenic toxicity. Here, we show that the microbiome protects mice from arsenic-induced mortality. Both antibiotic-treated and germ-free mice excrete less arsenic in stool and accumulate more arsenic in organs compared to control mice. Mice lacking the primary arsenic detoxification enzyme (As3mt) are hypersensitive to arsenic after antibiotic treatment or when derived germ-free, compared to wild-type and/or conventional counterparts. Human microbiome (stool) transplants protect germ-free As3mt-KO mice from arsenic-induced mortality, but protection depends on microbiome stability and the presence of specific bacteria, including Faecalibacterium. Our results demonstrate that both a functional As3mt and specific microbiome members are required for protection against acute arsenic toxicity in mouse models. We anticipate that the gut microbiome will become an important explanatory factor of disease (arsenicosis) penetrance in humans, and a novel target for prevention and treatment strategies.}, }
@article {pmid30573380, year = {2019}, author = {Altomare, A and Putignani, L and Del Chierico, F and Cocca, S and Angeletti, S and Ciccozzi, M and Tripiciano, C and Dalla Piccola, B and Cicala, M and Guarino, MPL}, title = {Gut mucosal-associated microbiota better discloses inflammatory bowel disease differential patterns than faecal microbiota.}, journal = {Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver}, volume = {51}, number = {5}, pages = {648-656}, doi = {10.1016/j.dld.2018.11.021}, pmid = {30573380}, issn = {1878-3562}, mesh = {Bacteria/*classification ; Case-Control Studies ; Colon/pathology ; Feces/*microbiology ; Female ; *Gastrointestinal Microbiome ; Humans ; Inflammatory Bowel Diseases/*microbiology ; Intestinal Mucosa/*microbiology/pathology ; Male ; Middle Aged ; RNA, Ribosomal, 16S/genetics ; }, abstract = {BACKGROUND: Growing evidence supports the potential role of intestinal microbiota in the pathophysiology of inflammatory bowel diseases (IBD) even if the literature does not reveal uniform alterations. The aim of the study was to evaluate the mucosal (MM) and faecal microbiota (FM) composition in a cohort of IBD patients compared to healthy controls (CTRLs).<br><br>METHODS: Faecal and mucosal samples were collected from 14 IBD patients and 11 CTRLs. The V1-V3 region of 16S rRNA locus was amplified on a 454-Junior Genome Sequencer. Reads were grouped into operational taxonomic units (OTUs) at a sequence similarity level of 97% for taxonomic assignment, and aligned for OTUs matching against Greengenes database.<br><br>RESULTS: Irrespective of disease localization and activity, in the MM of IBD patients a statistically significant increase of Proteobacteria (especially Enterobacteriaceae, Acidaminococcus, Veillonella dispar) and decrease of Firmicutes (especially Roseburia and Faecalibacterium prausnitzii) and Actinobacteria was found compared to CTRLs. In the colon district some specific bacterial biomarkers were identified: Enterobacteriaceae for IBD stools, Bacteroides for IBD biopsies, Mogibacteriaceae, Ruminococcaceae and Prevotella for CTRL stools, Ruminococcaceae for CTRL biopsies.<br><br>CONCLUSIONS: The profiles of FM were more similar to CTRLs, suggesting that microbiota adhering to the gut mucosa better discriminates patients from controls, with the identification of some interesting biomarkers.}, }
@article {pmid30572622, year = {2018}, author = {Sánchez-Ponce, Y and Varela-Fascinetto, G and Romo-Vázquez, JC and López-Martínez, B and Sánchez-Huerta, JL and Parra-Ortega, I and Fuentes-Pananá, EM and Morales-Sánchez, A}, title = {Simultaneous Detection of Beta and Gamma Human Herpesviruses by Multiplex qPCR Reveals Simple Infection and Coinfection Episodes Increasing Risk for Graft Rejection in Solid Organ Transplantation.}, journal = {Viruses}, volume = {10}, number = {12}, pages = {}, pmid = {30572622}, issn = {1999-4915}, mesh = {Adolescent ; Child ; Coinfection/*diagnosis/virology ; DNA Primers/genetics ; DNA, Viral/blood ; Epstein-Barr Virus Infections/*diagnosis/virology ; Female ; Graft Rejection/*etiology/virology ; Herpesvirus 4, Human/genetics ; Herpesvirus 6, Human/genetics ; Herpesvirus 7, Human/genetics ; Humans ; Male ; Multiplex Polymerase Chain Reaction ; Organ Transplantation/*adverse effects ; Prospective Studies ; Roseolovirus Infections/*diagnosis/virology ; Sensitivity and Specificity ; Viral Load ; }, abstract = {Herpesviruses are common components of the human microbiome that become clinically relevant when a competent immunosurveillance is compromised, such as in transplantation. Members of the beta and gamma subfamilies are associated with a wide diversity of pathologies, including end-organ disease and cancer. In this study, we developed a multiplex qPCR technique with high specificity, sensitivity, efficiency and predictability that allowed the simultaneous detection and quantification of beta and gamma human herpesviruses. The technique was tested in a cohort of 34 kidney- or liver-transplanted pediatric patients followed up for up to 12 months post-transplant. Viral load was determined in 495 leukocyte-plasma paired samples collected bi-weekly or monthly. Human herpesvirus (HHV) 7 was the herpesvirus most frequently found in positive samples (39%), followed by Epstein-Barr virus (EBV) (20%). Also, EBV and HHV7 were present in the majority of coinfection episodes (62%). The share of positive samples exclusively detected either in leukocytes or plasma was 85%, suggesting that these herpesviruses tended to take a latent or lytic path in an exclusive manner. Infection by human cytomegalovirus (HCMV) and HHV6, as well as coinfection by EBV/HHV7 and EBV/HHV6/HHV7, were associated with graft rejection (RR = 40.33 (p = 0.0013), 5.60 (p = 0.03), 5.60 (p = 0.03) and 17.64 (p = 0.0003), respectively). The routine monitoring of beta and gamma herpesviruses should be mandatory in transplant centers to implement preventive strategies.}, }
@article {pmid30564562, year = {2018}, author = {Proal, A and Marshall, T}, title = {Myalgic Encephalomyelitis/Chronic Fatigue Syndrome in the Era of the Human Microbiome: Persistent Pathogens Drive Chronic Symptoms by Interfering With Host Metabolism, Gene Expression, and Immunity.}, journal = {Frontiers in pediatrics}, volume = {6}, number = {}, pages = {373}, pmid = {30564562}, issn = {2296-2360}, abstract = {The illness ME/CFS has been repeatedly tied to infectious agents such as Epstein Barr Virus. Expanding research on the human microbiome now allows ME/CFS-associated pathogens to be studied as interacting members of human microbiome communities. Humans harbor these vast ecosystems of bacteria, viruses and fungi in nearly all tissue and blood. Most well-studied inflammatory conditions are tied to dysbiosis or imbalance of the human microbiome. While gut microbiome dysbiosis has been identified in ME/CFS, microbes and viruses outside the gut can also contribute to the illness. Pathobionts, and their associated proteins/metabolites, often control human metabolism and gene expression in a manner that pushes the body toward a state of illness. Intracellular pathogens, including many associated with ME/CFS, drive microbiome dysbiosis by directly interfering with human transcription, translation, and DNA repair processes. Molecular mimicry between host and pathogen proteins/metabolites further complicates this interference. Other human pathogens disable mitochondria or dysregulate host nervous system signaling. Antibodies and/or clonal T cells identified in patients with ME/CFS are likely activated in response to these persistent microbiome pathogens. Different human pathogens have evolved similar survival mechanisms to disable the host immune response and host metabolic pathways. The metabolic dysfunction driven by these organisms can result in similar clusters of inflammatory symptoms. ME/CFS may be driven by this pathogen-induced dysfunction, with the nature of dysbiosis and symptom presentation varying based on a patient's unique infectious and environmental history. Under such conditions, patients would benefit from treatments that support the human immune system in an effort to reverse the infectious disease process.}, }
@article {pmid30559213, year = {2018}, author = {Tedijanto, C and Olesen, SW and Grad, YH and Lipsitch, M}, title = {Estimating the proportion of bystander selection for antibiotic resistance among potentially pathogenic bacterial flora.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {51}, pages = {E11988-E11995}, pmid = {30559213}, issn = {1091-6490}, support = {R01 AI132606/AI/NIAID NIH HHS/United States ; U01 CK000538/CK/NCEZID CDC HHS/United States ; U01CK000538//ACL HHS/United States ; U54 GM088558/GM/NIGMS NIH HHS/United States ; }, mesh = {Adolescent ; Adult ; Anti-Bacterial Agents/immunology/*pharmacology ; Bacteria/classification/*drug effects/immunology ; Child ; Child, Preschool ; Drug Resistance, Bacterial/*drug effects/immunology ; Escherichia coli/drug effects ; Humans ; Infant ; Infant, Newborn ; Microbial Sensitivity Tests/methods ; Microbiota/*drug effects/immunology ; Pneumococcal Infections ; Pneumococcal Vaccines/immunology ; Species Specificity ; Staphylococcus aureus/drug effects ; Streptococcus pneumoniae/drug effects ; United States ; Vaccination ; Vaccines, Conjugate/immunology ; Young Adult ; }, abstract = {Bystander selection-the selective pressure for resistance exerted by antibiotics on microbes that are not the target pathogen of treatment-is critical to understanding the total impact of broad-spectrum antibiotic use on pathogenic bacterial species that are often carried asymptomatically. However, to our knowledge, this effect has never been quantified. We quantify bystander selection for resistance for a range of clinically relevant antibiotic-species pairs as the proportion of all antibiotic exposures received by a species for conditions in which that species was not the causative pathogen ("proportion of bystander exposures"). Data sources include the 2010-2011 National Ambulatory Medical Care Survey and National Hospital Ambulatory Medical Care Survey, the Human Microbiome Project, and additional carriage and etiological data from existing literature. For outpatient prescribing in the United States, we find that this proportion over all included antibiotic classes is over 80% for eight of nine organisms of interest. Low proportions of bystander exposure are often associated with infrequent bacterial carriage or concentrated prescribing of a particular antibiotic for conditions caused by the species of interest. Applying our results, we roughly estimate that pneumococcal conjugate vaccination programs result in nearly the same proportional reduction in total antibiotic exposures of Streptococcus pneumoniae, Staphylococcus aureus, and Escherichia coli, despite the latter two organisms not being targeted by the vaccine. These results underscore the importance of considering antibiotic exposures of bystanders, in addition to the target pathogen, in measuring the impact of antibiotic resistance interventions.}, }
@article {pmid30559176, year = {2018}, author = {Relman, DA and Lipsitch, M}, title = {Microbiome as a tool and a target in the effort to address antimicrobial resistance.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {51}, pages = {12902-12910}, pmid = {30559176}, issn = {1091-6490}, support = {R01 AI112401/AI/NIAID NIH HHS/United States ; R01 GM099534/GM/NIGMS NIH HHS/United States ; }, mesh = {Anti-Infective Agents/*pharmacology ; Communicable Disease Control/*methods ; Communicable Diseases/drug therapy ; Drug Resistance, Microbial/*drug effects/genetics ; Host Microbial Interactions/drug effects/genetics/immunology ; Humans ; Microbiota/*drug effects ; Vaccines/*therapeutic use ; }, abstract = {Reciprocal, intimate relationships between the human microbiome and the host immune system are shaped by past microbial encounters and prepare the host for future ones. Antibiotics and other antimicrobials leave their mark on both the microbiome and host immunity. Antimicrobials alter the structure of the microbiota, expand the host-specific pool of antimicrobial-resistance genes and organisms, degrade the protective effects of the microbiota against invasion by pathogens, and may impair vaccine efficacy. Through these effects on the microbiome they may affect immune responses. Vaccines that exert protective or therapeutic effects against pathogens may reduce the use of antimicrobials, the development and spread of antimicrobial resistance, and the harmful impacts of these drugs on the microbiome. Other strategies involving manipulation of the microbiome to deplete antibiotic-resistant organisms or to enhance immune responses to vaccines may prove valuable in addressing antimicrobial resistance as well. This article describes the intersections of immunity, microbiome and antimicrobial exposure, and the use of vaccines and other alternative strategies for the control and management of antimicrobial resistance.}, }
@article {pmid30551740, year = {2018}, author = {Romani, L and Pane, S and Severini, C and Menegon, M and Foglietta, G and Bernardi, S and Tchidjou, HK and Onetti Muda, A and Palma, P and Putignani, L}, title = {Challenging diagnosis of congenital malaria in non-endemic areas.}, journal = {Malaria journal}, volume = {17}, number = {1}, pages = {470}, pmid = {30551740}, issn = {1475-2875}, support = {RC2018//Bambino Ges&#xf9; Children's Hospital/ ; }, mesh = {Communicable Diseases, Imported/*diagnosis/parasitology ; Fetal Diseases/*diagnosis/parasitology ; Humans ; Infant ; Italy ; Malaria, Falciparum/*diagnosis/epidemiology ; Male ; Plasmodium falciparum/isolation &amp; purification ; Polymerase Chain Reaction ; }, abstract = {BACKGROUND: Congenital malaria is usually defined as the detection of asexual forms of Plasmodium spp. in a blood sample of a neonate during perinatal age if there is no possibility of postpartum infection by a mosquito bite. The incidence of congenital malaria is highly variable and seems related to several factors, such as different diagnostic methods for Plasmodium spp. detection, and area in which the epidemiologic analyses are performed. In non-endemic countries, cases of congenital malaria are rare. Hereby, a case of a congenital malaria in an HIV exposed child is reported.<br><br>CASE PRESENTATION: A 2-month-old male child was admitted to Bambino Ges&#xf9; Children's Hospital due to anaemia and exposure to HIV. He was born prematurely in Italy by cesarean section at 34&#xa0;weeks' gestation after a bicorial, biamniotic pregnancy by a migrant woman from Nigeria. He was the first of non-identical twins. Combined with anaemia, spleen and liver enlargement was noted, malaria was hypothesized. Malaria laboratory panel was performed on the newborn, mother and other twin blood samples, as follows: (i) malaria rapid diagnostic test (RDT); (ii) Giemsa-stained thick and thin blood smears for Plasmodium spp. identification and parasitaemia titration; (iii) molecular screening and typing of Plasmodium spp. by multiplex qualitative PCR assay based on 18S rRNA gene. Genotyping of Plasmodium falciparum isolates from mother and child was performed by neutral microsatellite and highly polymorphic marker amplification.<br><br>CONCLUSIONS: The maternal RDT sample was negative, while the infant RDT was positive; in both cases microscopy of blood smears and PCR showed infection with P. falciparum. Two of the genotypic molecular markers displayed different allelic variants between the two samples. This difference could imply infection multiplicity of the mother during the pregnancy, possibly harbouring more than one isolate, only one of them being transmitted to the newborn while the other persisting in the mother's blood. Because of the increasing number of pregnant women coming from endemic areas for malaria, an accurate anamnesis of infant's mother, and the inclusion of Plasmodium spp. research into TORCH screenings for mother-infant pair at birth, aiming at reducing morbidity and mortality associated to the disease might be suitable.}, }
@article {pmid30544936, year = {2018}, author = {D'Argenio, V}, title = {The Prenatal Microbiome: A New Player for Human Health.}, journal = {High-throughput}, volume = {7}, number = {4}, pages = {}, pmid = {30544936}, issn = {2571-5135}, abstract = {The last few years have featured an increasing interest in the study of the human microbiome and its correlations with health status. Indeed, technological advances have allowed the study of microbial communities to reach a previously unthinkable sensitivity, showing the presence of microbes also in environments usually considered as sterile. In this scenario, microbial communities have been described in the amniotic fluid, the umbilical blood cord, and the placenta, denying a dogma of reproductive medicine that considers the uterus like a sterile womb. This prenatal microbiome may play a role not only in fetal development but also in the predisposition to diseases that may develop later in life, and also in adulthood. Thus, the aim of this review is to report the current knowledge regarding the prenatal microbiome composition, its association with pathological processes, and the future perspectives regarding its manipulation for healthy status promotion and maintenance.}, }
@article {pmid30524957, year = {2018}, author = {Yang, J and Mu, X and Wang, Y and Zhu, D and Zhang, J and Liang, C and Chen, B and Wang, J and Zhao, C and Zuo, Z and Heng, X and Zhang, C and Zhang, L}, title = {Dysbiosis of the Salivary Microbiome Is Associated With Non-smoking Female Lung Cancer and Correlated With Immunocytochemistry Markers.}, journal = {Frontiers in oncology}, volume = {8}, number = {}, pages = {520}, pmid = {30524957}, issn = {2234-943X}, abstract = {Background: Association between oral bacteria and increased risk of lung cancer have been reported in several previous studies, however, the potential association between salivary microbiome and lung cancer in non-smoking women have not been evaluated. There is also no report on the relationship between immunocytochemistry markers and salivary microbiota. Method: In this study, we assessed the salivary microbiome of 75 non-smoking female lung cancer patients and 172 matched healthy individuals using 16S rRNA gene amplicon sequencing. We also calculated the Spearman's rank correlation coefficient between salivary microbiota and three immunohistochemical markers (TTF-1, Napsin A and CK7). Result: We analyzed the salivary microbiota of 247 subjects and found that non-smoking female lung cancer patients exhibited oral microbial dysbiosis. There was significantly lower microbial diversity and richness in lung cancer patients when compared to the control group (Shannon index, P < 0.01; Ace index, P < 0.0001). Based on the analysis of similarities, the composition of the microbiota in lung cancer patients also differed from that of the control group (r = 0.454, P < 0.001, unweighted UniFrac; r = 0.113, P < 0.01, weighted UniFrac). The bacterial genera Sphingomonas (P < 0.05) and Blastomonas (P < 0.0001) were relatively higher in non-smoking female lung cancer patients, whereas Acinetobacter (P < 0.001) and Streptococcus (P < 0.01) were higher in controls. Based on Spearman's correlation analysis, a significantly positive correlation can be observed between CK7 and Enterobacteriaceae (r = 0.223, P < 0.05). At the same time, Napsin A was positively associated with genera Blastomonas (r = 0.251, P < 0.05). TTF-1 exhibited a significantly positive correlation with Enterobacteriaceae (r = 0.262, P < 0.05). Functional analysis from inferred metagenomes indicated that oral microbiome in non-smoking female lung cancer patients were related to cancer pathways, p53 signaling pathway, apoptosis and tuberculosis. Conclusions: The study identified distinct salivary microbiome profiles in non-smoking female lung cancer patients, revealed potential correlations between salivary microbiome and immunocytochemistry markers used in clinical diagnostics, and provided proof that salivary microbiota can be an informative source for discovering non-invasive lung cancer biomarkers.}, }
@article {pmid30534599, year = {2018}, author = {Escapa, IF and Chen, T and Huang, Y and Gajare, P and Dewhirst, FE and Lemon, KP}, title = {New Insights into Human Nostril Microbiome from the Expanded Human Oral Microbiome Database (eHOMD): a Resource for the Microbiome of the Human Aerodigestive Tract.}, journal = {mSystems}, volume = {3}, number = {6}, pages = {}, pmid = {30534599}, issn = {2379-5077}, support = {R01 AI101018/AI/NIAID NIH HHS/United States ; R01 DE024468/DE/NIDCR NIH HHS/United States ; R01 DE016937/DE/NIDCR NIH HHS/United States ; R37 DE016937/DE/NIDCR NIH HHS/United States ; UL1 TR001102/TR/NCATS NIH HHS/United States ; R01 GM117174/GM/NIGMS NIH HHS/United States ; }, abstract = {The expanded Human Oral Microbiome Database (eHOMD) is a comprehensive microbiome database for sites along the human aerodigestive tract that revealed new insights into the nostril microbiome. The eHOMD provides well-curated 16S rRNA gene reference sequences linked to available genomes and enables assignment of species-level taxonomy to most next-generation sequences derived from diverse aerodigestive tract sites, including the nasal passages, sinuses, throat, esophagus, and mouth. Using minimum entropy decomposition coupled with the RDP Classifier and our eHOMD V1-V3 training set, we reanalyzed 16S rRNA V1-V3 sequences from the nostrils of 210 Human Microbiome Project participants at the species level, revealing four key insights. First, we discovered that Lawsonella clevelandensis, a recently named bacterium, and Neisseriaceae [G-1] HMT-174, a previously unrecognized bacterium, are common in adult nostrils. Second, just 19 species accounted for 90% of the total sequences from all participants. Third, 1 of these 19 species belonged to a currently uncultivated genus. Fourth, for 94% of the participants, 2 to 10 species constituted 90% of their sequences, indicating that the nostril microbiome may be represented by limited consortia. These insights highlight the strengths of the nostril microbiome as a model system for studying interspecies interactions and microbiome function. Also, in this cohort, three common nasal species (Dolosigranulum pigrum and two Corynebacterium species) showed positive differential abundance when the pathobiont Staphylococcus aureus was absent, generating hypotheses regarding colonization resistance. By facilitating species-level taxonomic assignment to microbes from the human aerodigestive tract, the eHOMD is a vital resource enhancing clinical relevance of microbiome studies. IMPORTANCE The eHOMD (http://www.ehomd.org) is a valuable resource for researchers, from basic to clinical, who study the microbiomes and the individual microbes in body sites in the human aerodigestive tract, which includes the nasal passages, sinuses, throat, esophagus, and mouth, and the lower respiratory tract, in health and disease. The eHOMD is an actively curated, web-based, open-access resource. eHOMD provides the following: (i) species-level taxonomy based on grouping 16S rRNA gene sequences at 98.5% identity, (ii) a systematic naming scheme for unnamed and/or uncultivated microbial taxa, (iii) reference genomes to facilitate metagenomic, metatranscriptomic, and proteomic studies and (iv) convenient cross-links to other databases (e.g., PubMed and Entrez). By facilitating the assignment of species names to sequences, the eHOMD is a vital resource for enhancing the clinical relevance of 16S rRNA gene-based microbiome studies, as well as metagenomic studies.}, }
@article {pmid30532649, year = {2018}, author = {Lim, MY and Cho, Y and Rho, M}, title = {Diverse Distribution of Resistomes in the Human and Environmental Microbiomes.}, journal = {Current genomics}, volume = {19}, number = {8}, pages = {701-711}, pmid = {30532649}, issn = {1389-2029}, abstract = {The routine therapeutic use of antibiotics has caused resistance genes to be disseminated across microbial populations. In particular, bacterial strains having antibiotic resistance genes are frequently observed in the human microbiome. Moreover, multidrug-resistant pathogens are now widely spread, threatening public health. Such genes are transferred and spread among bacteria even in different environments. Advances in high throughput sequencing technology and computational algorithms have accelerated investigation into antibiotic resistance genes of bacteria. Such studies have revealed that the antibiotic resistance genes are located close to the mobility-associated genes, which promotes their dissemination. An increasing level of information on genomic sequences of resistome should expedite research on drug-resistance in our body and environment, thereby contributing to the development of public health policy. In this review, the high prevalence of antibiotic resistance genes and their exchange in the human and environmental microbiome is discussed with respect to the genomic contents. The relationships among diverse resistomes, related bacterial species, and the antibiotics are reviewed. In addition, recent advances in bioinformatics approaches to investigate such relationships are discussed.}, }
@article {pmid30530088, year = {2019}, author = {Ben, Y and Fu, C and Hu, M and Liu, L and Wong, MH and Zheng, C}, title = {Human health risk assessment of antibiotic resistance associated with antibiotic residues in the environment: A review.}, journal = {Environmental research}, volume = {169}, number = {}, pages = {483-493}, doi = {10.1016/j.envres.2018.11.040}, pmid = {30530088}, issn = {1096-0953}, mesh = {*Anti-Bacterial Agents ; *Bacteria ; *Drug Resistance, Microbial ; Humans ; Risk Assessment ; }, abstract = {The extensive use of antibiotics leading to the rapid spread of antibiotic resistance poses high health risks to humans, but to date there is still lack of a quantitative model to properly assess the risks. Concerns over the health risk of antibiotic residues in the environment are mainly (1) the potential hazard of ingested antibiotic residues in the environment altering the human microbiome and promoting emergence and selection for bacteria resistance inhabiting the human body, and (2) the potential hazard of creating a selection pressure on environmental microbiome and leading to reservoirs of antibiotic resistance in the environment. We provide a holistic view of health risk assessment of antibiotic resistance associated with antibiotic residues in the environment in contrast with that of the antibiotic resistant bacteria and discuss the main knowledge gaps and the future research that should be prioritized to achieve the quantitative risk assessment. We examined and summarized the available data and information on the four core elements of antibiotic resistance associated with antibiotic residues in the environment: hazard identification, exposure assessment, dose-response assessment, and risk characterization. The data required to characterize the risks of antibiotic residues in the environment is severely limited. The main future research needs have been identified to enable better assessments of antibiotic resistance associated with antibiotic residues in the environment: (1) establishment of a standardized monitoring guide of antibiotic residues and antibiotic resistance in the environment, (2) derivation of the relationship between antibiotic levels and pathogenic antibiotic-resistance development in different settings, and (3) establishment of the dose-response relationship between pathogenic antibiotic resistant bacteria and various infection diseases. After identification of key risk determinant parameters, we propose a conceptual framework of human health risk assessments of antibiotic residues in the environment. CAPSULE: A holistic view of human health risk assessment of antibiotic residues in the environment was provided.}, }
@article {pmid30529020, year = {2019}, author = {Robertson, RC and Manges, AR and Finlay, BB and Prendergast, AJ}, title = {The Human Microbiome and Child Growth - First 1000 Days and Beyond.}, journal = {Trends in microbiology}, volume = {27}, number = {2}, pages = {131-147}, doi = {10.1016/j.tim.2018.09.008}, pmid = {30529020}, issn = {1878-4380}, support = {108065/Z/15/Z/WT_/Wellcome Trust/United Kingdom ; 206455/Z/17/Z/WT_/Wellcome Trust/United Kingdom ; MR/M007367/1/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Bacteria/classification ; Child, Preschool ; Environment ; Female ; Gastrointestinal Microbiome/immunology/physiology ; Gastrointestinal Tract/*microbiology ; Growth and Development/immunology/*physiology ; *Host Microbial Interactions/immunology/physiology ; Humans ; Infant ; Infant, Newborn ; Infections ; Malnutrition ; *Microbiota/immunology/physiology ; Pregnancy ; }, abstract = {The assembly of microbial communities within the gastrointestinal tract during early life plays a critical role in immune, endocrine, metabolic, and other host developmental pathways. Environmental insults during this period, such as food insecurity and infections, can disrupt this optimal microbial succession, which may contribute to lifelong and intergenerational deficits in growth and development. Here, we review the human microbiome in the first 1000 days - referring to the period from conception to 2 years of age - and using a developmental model, we examine the role of early microbial succession in growth and development. We propose that an 'undernourished' microbiome is intergenerational, thereby perpetuating growth impairments into successive generations. We also identify and discuss the intertwining host-microbe-environment interactions occurring prenatally and during early infancy, which may impair the trajectories of healthy growth and development, and explore their potential as novel microbial targets for intervention.}, }
@article {pmid30526758, year = {2018}, author = {Blaser, MJ}, title = {Our missing microbes: Short-term antibiotic courses have long-term consequences.}, journal = {Cleveland Clinic journal of medicine}, volume = {85}, number = {12}, pages = {928-930}, doi = {10.3949/ccjm.85gr.18005}, pmid = {30526758}, issn = {1939-2869}, mesh = {Anti-Bacterial Agents/*adverse effects ; Humans ; Long Term Adverse Effects/*chemically induced/microbiology ; Microbiota/*drug effects ; }, }
@article {pmid30521647, year = {2018}, author = {Jeżewska-Frąckowiak, J and Seroczyńska, K and Banaszczyk, J and Jedrzejczak, G and Żylicz-Stachula, A and Skowron, PM}, title = {The promises and risks of probiotic Bacillus species.}, journal = {Acta biochimica Polonica}, volume = {65}, number = {4}, pages = {509-519}, doi = {10.18388/abp.2018_2652}, pmid = {30521647}, issn = {1734-154X}, mesh = {Bacillus/classification/genetics/*physiology ; Biofilms ; Drug Resistance, Bacterial ; Gastrointestinal Diseases/*microbiology/*prevention &amp; control ; *Gastrointestinal Microbiome ; Humans ; Probiotics/*administration &amp; dosage/*adverse effects/standards ; RNA, Ribosomal, 16S/genetics ; Risk ; }, abstract = {Supplementing the human microbiome with probiotic microorganisms is a proposed solution for civilization syndromes such as dysbiosis and gastrointestinal tract (GIT) disorders. Bimodal probiotic strains of the Bacillus genus constitute the microbiota of the human environment, and are typically found in soil, water, a number of non-dairy fermented foods, as well as in human and animal GIT. Probiotic Bacillus sp. are Gram positive rods, with the ability of sporulation to survive environmental stress and preparation conditions. In vitro models of the human stomach and human studies with probiotic Bacillus reveal the mechanisms of its life cycle and sporulation. The Bacillus sp. probiotic biofilm introduces biochemical effects such as antimicrobial and enzymatic activity, thus contributing to protection from GIT and other infections. Despite the beneficial activity of Bacillus strains belonging to the safety group 1, a number of strains can pose a substantial health risk, carrying genes for various toxins or antibiotic resistance. Commercially available Bacillus probiotic preparations include strains from the subtilis and other closely related phylogenetic clades. Those intended for oral administration in humans, often encapsulated with appropriate supporting materials, still tend to be mislabeled or poorly characterized. Bacillus sp. MALDI-TOF analysis, combined with sequencing of characteristic 16S rRNA or enzyme coding genes, may provide accurate identification. A promising future application of the probiotic Bacillus sp. might be the microflora biocontrol in the human body and the closest human environment. Environmental probiotic Bacillus species display the potential to support human microflora, however controversies regarding the safety of certain strains is a key factor in their still limited application.}, }
@article {pmid30521551, year = {2018}, author = {Vernocchi, P and Del Chierico, F and Russo, A and Majo, F and Rossitto, M and Valerio, M and Casadei, L and La Storia, A and De Filippis, F and Rizzo, C and Manetti, C and Paci, P and Ercolini, D and Marini, F and Fiscarelli, EV and Dallapiccola, B and Lucidi, V and Miccheli, A and Putignani, L}, title = {Gut microbiota signatures in cystic fibrosis: Loss of host CFTR function drives the microbiota enterophenotype.}, journal = {PloS one}, volume = {13}, number = {12}, pages = {e0208171}, pmid = {30521551}, issn = {1932-6203}, mesh = {Anti-Bacterial Agents/adverse effects ; Bacteria/*isolation &amp; purification ; Child, Preschool ; Cohort Studies ; Cystic Fibrosis/drug therapy/genetics/*physiopathology ; Cystic Fibrosis Transmembrane Conductance Regulator/*genetics ; Dysbiosis/microbiology/physiopathology ; Exocrine Pancreatic Insufficiency/genetics/physiopathology ; Feces/microbiology ; Female ; Gastrointestinal Microbiome/drug effects/*physiology ; Host Microbial Interactions/physiology ; Humans ; Intestinal Mucosa/microbiology/*physiopathology ; Male ; Metabolomics ; Metagenomics ; Phenotype ; }, abstract = {BACKGROUND: Cystic fibrosis (CF) is a disorder affecting the respiratory, digestive, reproductive systems and sweat glands. This lethal hereditary disease has known or suspected links to the dysbiosis gut microbiota. High-throughput meta-omics-based approaches may assist in unveiling this complex network of symbiosis modifications.<br><br>OBJECTIVES: The aim of this study was to provide a predictive and functional model of the gut microbiota enterophenotype of pediatric patients affected by CF under clinical stability.<br><br>METHODS: Thirty-one fecal samples were collected from CF patients and healthy children (HC) (age range, 1-6 years) and analysed using targeted-metagenomics and metabolomics to characterize the ecology and metabolism of CF-linked gut microbiota. The multidimensional data were low fused and processed by chemometric classification analysis.<br><br>RESULTS: The fused metagenomics and metabolomics based gut microbiota profile was characterized by a high abundance of Propionibacterium, Staphylococcus and Clostridiaceae, including Clostridium difficile, and a low abundance of Eggerthella, Eubacterium, Ruminococcus, Dorea, Faecalibacterium prausnitzii, and Lachnospiraceae, associated with overexpression of 4-aminobutyrate (GABA), choline, ethanol, propylbutyrate, and pyridine and low levels of sarcosine, 4-methylphenol, uracil, glucose, acetate, phenol, benzaldehyde, and methylacetate. The CF gut microbiota pattern revealed an enterophenotype intrinsically linked to disease, regardless of age, and with dysbiosis uninduced by reduced pancreatic function and only partially related to oral antibiotic administration or lung colonization/infection.<br><br>CONCLUSIONS: All together, the results obtained suggest that the gut microbiota enterophenotypes of CF, together with endogenous and bacterial CF biomarkers, are direct expression of functional alterations at the intestinal level. Hence, it's possible to infer that CFTR impairment causes the gut ecosystem imbalance.This new understanding of CF host-gut microbiota interactions may be helpful to rationalize novel clinical interventions to improve the affected children's nutritional status and intestinal function.}, }
@article {pmid30519775, year = {2019}, author = {Slobodin, G and Rosner, I and Kessel, A}, title = {Dendritic cells in the pathogenesis of ankylosing spondylitis and axial spondyloarthritis.}, journal = {Clinical rheumatology}, volume = {38}, number = {5}, pages = {1231-1235}, pmid = {30519775}, issn = {1434-9949}, mesh = {Dendritic Cells/*immunology ; HLA-B27 Antigen/genetics/immunology ; Humans ; Interleukin-17/immunology ; Spondylarthritis/*genetics/*immunology ; Spondylitis, Ankylosing/genetics/immunology ; T-Lymphocytes/immunology ; }, abstract = {The interaction of dendritic cells (DCs) with the human microbiome, with distorted handling of the microbiota or its products via the direct effect of HLA B27, probably represents the initial element in the chain of events leading to the development of clinical axial spondyloarthritis. The mechanism of disease extension onto the skeleton and other tissues involved, such as uvea, may also involve migratory DCs. Finally, the role of DCs in the initiation of the inflammatory tissue response with activation of the IL-17 axis has been demonstrated. Further, some initial data suggests the possible connection of DCs with disease-related new bone formation.}, }
@article {pmid30507717, year = {2019}, author = {Lai, PS and Christiani, DC}, title = {Impact of occupational exposure on human microbiota.}, journal = {Current opinion in allergy and clinical immunology}, volume = {19}, number = {2}, pages = {86-91}, pmid = {30507717}, issn = {1473-6322}, support = {K23 ES023700/ES/NIEHS NIH HHS/United States ; R01 AI144119/AI/NIAID NIH HHS/United States ; T42 OH008416/OH/NIOSH CDC HHS/United States ; }, mesh = {Animals ; Endotoxins ; *Gastrointestinal Microbiome ; Humans ; Metals, Heavy ; Military Personnel ; Occupational Exposure/*adverse effects ; Particulate Matter ; Persian Gulf Syndrome/*etiology ; Workplace ; }, abstract = {PURPOSE OF REVIEW: Recent evidence suggests that environmental exposures change the adult human microbiome. Here, we review recent evidence on the impact of the work microbiome and work-related chemical, metal and particulate exposures on the human microbiome.<br><br>RECENT FINDINGS: Prior literature on occupational microbial exposures has focused mainly on the respiratory effects of endotoxin, but a recent study suggests that not all endotoxin is the same; endotoxin from some species is proinflammatory, whereas endotoxin from other species is anti-inflammatory. Work with animals can change the adult human microbiome, likely through colonization. Early studies in military personnel and animal models of gulf war illness show that military exposures change the gut microbiome and increase gut permeability. Heavy metal and particulate matter exposure, which are often elevated in occupational settings, also change the gut microbiome.<br><br>SUMMARY: An emerging body of literature shows that work-related exposures can change the human microbiome. The health effects of these changes are currently not well studied. If work exposures lead to disease through alterations in the human microbiome, exposure cessation without addressing changes to the human microbiome may be ineffective for disease prevention and treatment.}, }
@article {pmid30514510, year = {2018}, author = {O'Toole, RF and Gautam, SS}, title = {The host microbiome and impact of tuberculosis chemotherapy.}, journal = {Tuberculosis (Edinburgh, Scotland)}, volume = {113}, number = {}, pages = {26-29}, doi = {10.1016/j.tube.2018.08.015}, pmid = {30514510}, issn = {1873-281X}, mesh = {Animals ; Antitubercular Agents/adverse effects/*therapeutic use ; Drug Therapy, Combination ; Dysbiosis ; Gastrointestinal Microbiome/*drug effects ; Host-Pathogen Interactions ; Humans ; Lung/*drug effects/microbiology ; Mycobacterium tuberculosis/*drug effects/pathogenicity ; Risk Factors ; Treatment Outcome ; Tuberculosis/diagnosis/*drug therapy/microbiology ; }, abstract = {The treatment of Mycobacterium tuberculosis infection is often viewed in isolation from other human microbial symbionts. Understandably, the clinical priority is eliminating active or latent tuberculosis (TB) in patients. With the increasing resolution of molecular biology technologies, it is becoming apparent that antibiotic treatment can perturb the homeostasis of the host microbiome. For example, dysbiosis of the gut microbiota has been associated with an increased risk of the development of asthma, obesity and diabetes. Therefore, fundamental questions include: Does TB chemotherapy cause disruption of the human microbiome and adverse effects in patients; and are there signature taxa of dysbiosis following TB treatment. In this review, we examine recent research on the detection of changes in the microbiome during antibiotic administration and discuss specific findings that relate to the impact of anti-tubercular chemotherapy.}, }
@article {pmid30510919, year = {2018}, author = {Brenner, LA and Hoisington, AJ and Stearns-Yoder, KA and Stamper, CE and Heinze, JD and Postolache, TT and Hadidi, DA and Hoffmire, CA and Stanislawski, MA and Lowry, CA}, title = {Military-Related Exposures, Social Determinants of Health, and Dysbiosis: The United States-Veteran Microbiome Project (US-VMP).}, journal = {Frontiers in cellular and infection microbiology}, volume = {8}, number = {}, pages = {400}, pmid = {30510919}, issn = {2235-2988}, mesh = {Adult ; Aged ; Cohort Studies ; *Dysbiosis ; Female ; Humans ; Male ; Mental Health ; *Microbiota ; Middle Aged ; Military Personnel/*psychology ; *Social Determinants of Health ; United States ; United States Department of Veterans Affairs ; Veterans ; *Veterans Health ; Young Adult ; }, abstract = {Significant effort has been put forth to increase understanding regarding the role of the human microbiome in health- and disease-related processes. In turn, the United States (US) Veteran Microbiome Project (US-VMP) was conceptualized as a means by which to serially collect microbiome and health-related data from those seeking care within the Veterans Health Administration (VHA). In this manuscript, exposures related to military experiences, as well as conditions and health-related factors among patients seen in VHA clinical settings are discussed in relation to common psychological and physical outcomes. Upon enrollment in the study, Veterans complete psychometrically sound (i.e., reliable and valid) measures regarding their past and current medical history. Participants also provide skin, oral, and gut microbiome samples, and permission to track their health status via the VHA electronic medical record. To date, data collection efforts have been cross-diagnostic. Within this manuscript, we describe current data collection practices and procedures, as well as highlight demographic, military, and psychiatric characteristics of the first 188 Veterans enrolled in the study. Based on these findings, we assert that this cohort is unique as compared to those enrolled in recent large-scale studies of the microbiome. To increase understanding regarding disease and health among diverse cohorts, efforts such as the US-VMP are vital. Ongoing barriers and facilitators to data collection are discussed, as well as future research directions, with an emphasis on the importance of shifting current thinking regarding the microbiome from a focus on normalcy and dysbiosis to health promotion and disease prevention.}, }
@article {pmid30510497, year = {2018}, author = {Mathias, M}, title = {Autointoxication and historical precursors of the microbiome-gut-brain axis.}, journal = {Microbial ecology in health and disease}, volume = {29}, number = {2}, pages = {1548249}, pmid = {30510497}, issn = {0891-060X}, abstract = {This article focuses on autointoxication, a discredited medical theory from the late nineteenth century that provides important points of reflection for today's research on the role of microbes in the human gut for mental health. It considers how the theory of autointoxication, which came into great prominence amongst physicians and the general public worldwide, fell from grace by the middle of the twentieth century, and briefly asks why studies of the human microbiome are now back in vogue. It departs from earlier articles on the topic firstly by arguing that autointoxication theory was especially prevalent in France, and secondly by focusing on the application of this theory to mental health. Bringing to light medical treatises and theses from this period which have so far remained unexamined, it shows that examining the development and reception of medical theories form the past can help us today in understanding both the pitfalls and promise of research in this area.}, }
@article {pmid30487377, year = {2018}, author = {Ando, H}, title = {[Creation of synthetic bacterial viruses].}, journal = {Nihon saikingaku zasshi. Japanese journal of bacteriology}, volume = {73}, number = {4}, pages = {201-210}, doi = {10.3412/jsb.73.201}, pmid = {30487377}, issn = {1882-4110}, mesh = {Bacteria/*virology ; Bacterial Infections/*therapy ; *Bacteriophages/genetics ; Drug Resistance, Bacterial ; *Genetic Engineering/methods ; *Genome, Viral/genetics ; Host Specificity ; Humans ; *Phage Therapy ; Polymerase Chain Reaction ; }, abstract = {Bacteria are closely related with human health and diseases. For example, the emergence of drug-resistant bacteria is a serious problem in the world. Studying the human microbiome shows its important role for our health. But we have very limited tools to edit bacterial population. Antibiotics are generally broad-spectrum and unable to kill only bad bacteria. The natural enemies of bacteria, called bacteriophage (phage), have highly specific host range, and thus promising candidates for targeted bacterial population editing. However, isolation and characterization of natural phages can be a time-, labor- and cost-intensive way. Also, developing phage-based therapeutics and diagnostics is limited by the difficulty of engineering phages. Here, I describe a phage genome-engineering platform and synthetic phages with tunable host ranges to overcome these challenges.}, }
@article {pmid30482830, year = {2018}, author = {Espinoza, JL and Harkins, DM and Torralba, M and Gomez, A and Highlander, SK and Jones, MB and Leong, P and Saffery, R and Bockmann, M and Kuelbs, C and Inman, JM and Hughes, T and Craig, JM and Nelson, KE and Dupont, CL}, title = {Supragingival Plaque Microbiome Ecology and Functional Potential in the Context of Health and Disease.}, journal = {mBio}, volume = {9}, number = {6}, pages = {}, pmid = {30482830}, issn = {2150-7511}, support = {R01 DE019665/DE/NIDCR NIH HHS/United States ; R01 GM120624/GM/NIGMS NIH HHS/United States ; }, mesh = {Australia ; Bacteria/*classification/*genetics ; Child ; Child, Preschool ; Dental Caries/*microbiology ; Dental Plaque/*microbiology ; Humans ; Metabolic Networks and Pathways/genetics ; Metagenomics ; *Microbiota ; Sequence Analysis, DNA ; }, abstract = {To address the question of how microbial diversity and function in the oral cavities of children relates to caries diagnosis, we surveyed the supragingival plaque biofilm microbiome in 44 juvenile twin pairs. Using shotgun sequencing, we constructed a genome encyclopedia describing the core supragingival plaque microbiome. Caries phenotypes contained statistically significant enrichments in specific genome abundances and distinct community composition profiles, including strain-level changes. Metabolic pathways that are statistically associated with caries include several sugar-associated phosphotransferase systems, antimicrobial resistance, and metal transport. Numerous closely related previously uncharacterized microbes had substantial variation in central metabolism, including the loss of biosynthetic pathways resulting in auxotrophy, changing the ecological role. We also describe the first complete Gracilibacteria genomes from the human microbiome. Caries is a microbial community metabolic disorder that cannot be described by a single etiology, and our results provide the information needed for next-generation diagnostic tools and therapeutics for caries.IMPORTANCE Oral health has substantial economic importance, with over $100 billion spent on dental care in the United States annually. The microbiome plays a critical role in oral health, yet remains poorly classified. To address the question of how microbial diversity and function in the oral cavities of children relate to caries diagnosis, we surveyed the supragingival plaque biofilm microbiome in 44 juvenile twin pairs. Using shotgun sequencing, we constructed a genome encyclopedia describing the core supragingival plaque microbiome. This unveiled several new previously uncharacterized but ubiquitous microbial lineages in the oral microbiome. Caries is a microbial community metabolic disorder that cannot be described by a single etiology, and our results provide the information needed for next-generation diagnostic tools and therapeutics for caries.}, }
@article {pmid30481125, year = {2018}, author = {Kim, JW and Lee, JS and Kim, JH and Jeong, JW and Lee, DH and Nam, S}, title = {Comparison of Microbiota Variation in Korean Healthy Adolescents with Adults Suggests Notable Maturity Differences.}, journal = {Omics : a journal of integrative biology}, volume = {22}, number = {12}, pages = {770-778}, pmid = {30481125}, issn = {1557-8100}, mesh = {Adolescent ; Gastrointestinal Microbiome/*genetics ; Humans ; Microbiota/*genetics ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, RNA/methods ; }, abstract = {Comparative studies of microbiome variation in world populations and different developmental stages of organisms are essential to decipher the linkages among microbiome, health, and disease. Notably, the gut microbiota are believed to mature in early life. In this context, we compared the gut microbiota diversity in Korean adolescent healthy samples (KAHSs) to healthy Korean adults (HKAs) as well as the Human Microbiome Project healthy samples (HMPHSs), the latter being one of the largest adult cohorts, based on organismal composition, alpha- and beta-diversities, function/pathway prediction analysis, and co-occurrence networks. We found that the gut microbiota compositions, including the ratios of firmicutes to bacteroidetes, between KAHSs and HMPHSs were different, and the diversities of KAHSs were less than those of HMPHSs. The predicted functions, for example, secondary bile acid synthesis and insulin signaling of KAHSs and HMPHSs, were also significantly different. Genus-level networks showed that co-occurrences among different taxa more frequently happened in HMPHSs than in KAHSs. Even though both KAHSs and HMPHSs represent healthy microbiomes, comparisons showed substantial differences, likely implicating different diets, environments, and demographics. Interestingly, we observed lower microbial diversities and less frequent co-occurrences among different taxa in KAHSs than adult HMPHSs and HKAs. These new findings collectively suggest that the adolescent gut microbiota in the present Korean sample did not reach the extent of maturity of adult microbiota diversity. In all, further population studies of microbiome variation across geographies and developmental stages are warranted, and should usefully inform future diagnostics and therapeutics innovation targeting the microbiome.}, }
@article {pmid30477563, year = {2018}, author = {Sinha, R and Ahsan, H and Blaser, M and Caporaso, JG and Carmical, JR and Chan, AT and Fodor, A and Gail, MH and Harris, CC and Helzlsouer, K and Huttenhower, C and Knight, R and Kong, HH and Lai, GY and Hutchinson, DLS and Le Marchand, L and Li, H and Orlich, MJ and Shi, J and Truelove, A and Verma, M and Vogtmann, E and White, O and Willett, W and Zheng, W and Mahabir, S and Abnet, C}, title = {Next steps in studying the human microbiome and health in prospective studies, Bethesda, MD, May 16-17, 2017.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {210}, pmid = {30477563}, issn = {2049-2618}, support = {P30 CA016520/CA/NCI NIH HHS/United States ; P30 DK043351/DK/NIDDK NIH HHS/United States ; }, mesh = {Computational Biology/*methods ; Humans ; Microbiota/*physiology ; Neoplasms/*etiology ; Prospective Studies ; Reproducibility of Results ; *Research Design ; }, abstract = {The National Cancer Institute (NCI) sponsored a 2-day workshop, "Next Steps in Studying the Human Microbiome and Health in Prospective Studies," in Bethesda, Maryland, May 16-17, 2017. The workshop brought together researchers in the field to discuss the challenges of conducting microbiome studies, including study design, collection and processing of samples, bioinformatics and statistical methods, publishing results, and ensuring reproducibility of published results. The presenters emphasized the great potential of microbiome research in understanding the etiology of cancer. This report summarizes the workshop and presents practical suggestions for conducting microbiome studies, from workshop presenters, moderators, and participants.}, }
@article {pmid30477107, year = {2018}, author = {Cristofori, F and Indrio, F and Miniello, VL and De Angelis, M and Francavilla, R}, title = {Probiotics in Celiac Disease.}, journal = {Nutrients}, volume = {10}, number = {12}, pages = {}, pmid = {30477107}, issn = {2072-6643}, mesh = {Animals ; Bacteria/*growth &amp; development ; Celiac Disease/*drug therapy/microbiology ; *Diet, Gluten-Free ; *Dysbiosis/complications/drug therapy ; *Gastrointestinal Microbiome ; Humans ; Probiotics/*therapeutic use ; }, abstract = {Recently, the interest in the human microbiome and its interplay with the host has exploded and provided new insights on its role in conferring host protection and regulating host physiology, including the correct development of immunity. However, in the presence of microbial imbalance and particular genetic settings, the microbiome may contribute to the dysfunction of host metabolism and physiology, leading to pathogenesis and/or the progression of several diseases. Celiac disease (CD) is a chronic autoimmune enteropathy triggered by dietary gluten exposure in genetically predisposed individuals. Despite ascertaining that gluten is the trigger in CD, evidence has indicated that intestinal microbiota is somehow involved in the pathogenesis, progression, and clinical presentation of CD. Indeed, several studies have reported imbalances in the intestinal microbiota of patients with CD that are mainly characterized by an increased abundance of Bacteroides spp. and a decrease in Bifidobacterium spp. The evidence that some of these microbial imbalances still persist in spite of a strict gluten-free diet and that celiac patients suffering from persistent gastrointestinal symptoms have a desert gut microbiota composition further support its close link with CD. All of this evidence gives rise to the hypothesis that probiotics might play a role in this condition. In this review, we describe the recent scientific evidences linking the gut microbiota in CD, starting from the possible role of microbes in CD pathogenesis, the attempt to define a microbial signature of disease, the effect of a gluten-free diet and host genetic assets regarding microbial composition to end in the exploration of the proof of concept of probiotic use in animal models to the most recent clinical application of selected probiotic strains.}, }
@article {pmid30474490, year = {2019}, author = {Jonsson, V and Österlund, T and Nerman, O and Kristiansson, E}, title = {Modelling of zero-inflation improves inference of metagenomic gene count data.}, journal = {Statistical methods in medical research}, volume = {28}, number = {12}, pages = {3712-3728}, doi = {10.1177/0962280218811354}, pmid = {30474490}, issn = {1477-0334}, mesh = {Bayes Theorem ; *Bias ; *Data Interpretation, Statistical ; Humans ; Linear Models ; Metagenomics/*statistics &amp; numerical data ; Monte Carlo Method ; Poisson Distribution ; }, abstract = {Metagenomics enables the study of gene abundances in complex mixtures of microorganisms and has become a standard methodology for the analysis of the human microbiome. However, gene abundance data is inherently noisy and contains high levels of biological and technical variability as well as an excess of zeros due to non-detected genes. This makes the statistical analysis challenging. In this study, we present a new hierarchical Bayesian model for inference of metagenomic gene abundance data. The model uses a zero-inflated overdispersed Poisson distribution which is able to simultaneously capture the high gene-specific variability as well as zero observations in the data. By analysis of three comprehensive datasets, we show that zero-inflation is common in metagenomic data from the human gut and, if not correctly modelled, it can lead to substantial reductions in statistical power. We also show, by using resampled metagenomic data, that our model has, compared to other methods, a higher and more stable performance for detecting differentially abundant genes. We conclude that proper modelling of the gene-specific variability, including the excess of zeros, is necessary to accurately describe gene abundances in metagenomic data. The proposed model will thus pave the way for new biological insights into the structure of microbial communities.}, }
@article {pmid30466159, year = {2019}, author = {Mendez, R and Banerjee, S and Bhattacharya, SK and Banerjee, S}, title = {Lung inflammation and disease: A perspective on microbial homeostasis and metabolism.}, journal = {IUBMB life}, volume = {71}, number = {2}, pages = {152-165}, pmid = {30466159}, issn = {1521-6551}, support = {P30 EY014801/EY/NEI NIH HHS/United States ; R21 HL125021/HL/NHLBI NIH HHS/United States ; }, mesh = {Actinobacteria/immunology/metabolism/pathogenicity ; Asthma/immunology/*metabolism/microbiology/pathology ; Cystic Fibrosis/immunology/*metabolism/microbiology/pathology ; Firmicutes/immunology/metabolism/pathogenicity ; Homeostasis/immunology ; Humans ; Lung/immunology/metabolism/microbiology/pathology ; Lung Neoplasms/immunology/*metabolism/microbiology/pathology ; Microbiota/immunology ; Pneumonia, Bacterial/immunology/*metabolism/microbiology/pathology ; Proteobacteria/immunology/metabolism/pathogenicity ; Pulmonary Disease, Chronic Obstructive/immunology/*metabolism/microbiology/pathology ; Respiratory Mucosa/immunology/metabolism/microbiology/pathology ; }, abstract = {It is now well appreciated that the human microbiome plays a significant role in a number of processes in the body, significantly affecting its metabolic, inflammatory, and immune homeostasis. Recent research has revealed that almost every mucosal surface in the human body is associated with a resident commensal microbiome of its own. While the gut microbiome and its role in regulation of host metabolism along with its alteration in a disease state has been well studied, there is a lacuna in understanding the resident microbiota of other mucosal surfaces. Among these, the scientific information on the role of lung microbiota in pulmonary diseases is currently severely limited. Historically, lungs have been considered to be sterile and lung diseases have only been studied in the context of bacterial pathogenesis. Recently however, studies have revealed a resilient microbiome in the upper and lower respiratory tracts and there is increased evidence on its central role in respiratory diseases. Knowledge of lung microbiome and its metabolic fallout (local and systemic) is still in its nascent stages and attracting immense interest in recent times. In this review, we will provide a perspective on lung-associated metabolic disorders defined for lung diseases (e.g., chronic obstructive pulmonary disease, asthma, and respiratory depression due to infection) and correlate it with lung microbial perturbation. Such perturbations may be due to altered biochemical or metabolic stress as well. Finally, we will draw evidence from microbiome and classical microbiology literature to demonstrate how specific lung morbidities associate with specific metabolic characteristics of the disease, and with the role of microbiome in this context. © 2018 IUBMB Life, 71(1):152-165, 2019.}, }
@article {pmid30466152, year = {2019}, author = {Beilsmith, K and Thoen, MPM and Brachi, B and Gloss, AD and Khan, MH and Bergelson, J}, title = {Genome-wide association studies on the phyllosphere microbiome: Embracing complexity in host-microbe interactions.}, journal = {The Plant journal : for cell and molecular biology}, volume = {97}, number = {1}, pages = {164-181}, doi = {10.1111/tpj.14170}, pmid = {30466152}, issn = {1365-313X}, mesh = {*Genome-Wide Association Study ; *Host Microbial Interactions ; *Microbiota ; Plants/*genetics/microbiology ; }, abstract = {Environmental sequencing shows that plants harbor complex communities of microbes that vary across environments. However, many approaches for mapping plant genetic variation to microbe-related traits were developed in the relatively simple context of binary host-microbe interactions under controlled conditions. Recent advances in sequencing and statistics make genome-wide association studies (GWAS) an increasingly promising approach for identifying the plant genetic variation associated with microbes in a community context. This review discusses early efforts on GWAS of the plant phyllosphere microbiome and the outlook for future studies based on human microbiome GWAS. A workflow for GWAS of the phyllosphere microbiome is then presented, with particular attention to how perspectives on the mechanisms, evolution and environmental dependence of plant-microbe interactions will influence the choice of traits to be mapped.}, }
@article {pmid30465353, year = {2018}, author = {Wang, H and Kang, D and Zhou, XD and Li, YQ}, title = {[Prevention of infectious diseases through microecology modulation techniques].}, journal = {Hua xi kou qiang yi xue za zhi = Huaxi kouqiang yixue zazhi = West China journal of stomatology}, volume = {36}, number = {5}, pages = {564-567}, pmid = {30465353}, issn = {2618-0456}, mesh = {Humans ; *Microbiota ; Mouth/microbiology ; Skin/microbiology ; }, abstract = {The microbe is small in volume, but large in quantity and species. The symbiotic microbe, which is far more than human cells, code millions times of genes than human being. Somatic cells and these symbiotic microbe distributing in human body skin, respiratory tract, oral cavity and gastrointestinal tract, urinary tract and other parts form a complex ecosystem whose dynamic balance is highly related to body health. With the successful implementation of Human Microbiome Project, more attentions have been paid to the next generation microbiome technologies. New tools and methods for ecological regulation of human microbiome are emerging. The way we improve the world of human microbiology will be more convenient. This paper will make a review on the modulation techniques of human microbiome.}, }
@article {pmid30460770, year = {2018}, author = {Barbara, G and Cremon, C and Azpiroz, F}, title = {Probiotics in irritable bowel syndrome: Where are we?.}, journal = {Neurogastroenterology and motility}, volume = {30}, number = {12}, pages = {e13513}, doi = {10.1111/nmo.13513}, pmid = {30460770}, issn = {1365-2982}, support = {SAF 2016-76648-R//Italian Ministry of Education, University and Research, and the Spanish Ministry of Economy and Competitiveness/International ; //Instituto de Salud Carlos III/International ; //University of Bologna RFO/International ; //Fondazione del Monte di Bologna e Ravenna/International ; }, mesh = {Animals ; Gastrointestinal Microbiome ; Humans ; Irritable Bowel Syndrome/*microbiology ; *Probiotics ; }, abstract = {We have only recently begun to understand how alterations of the intestinal microbial ecosystem lead to the disruption of host-microbial interactions and are associated with diseases, including functional gastrointestinal disorders such as irritable bowel syndrome (IBS). Although we are still far from understanding the human microbiome, gut microbiota is already a therapeutic target. Probiotics are live microorganisms that, when administered in adequate amounts, confer a health benefit to the host and may represent a therapeutic option for diseases characterized by dysbiosis such as IBS. Meta-analyses suggest that probiotics provide a therapeutic gain over placebo on global symptoms with a high safety profile in IBS patients. However, the mechanisms by which they provide benefit in IBS remain virtually unknown. In this issue of Neurogastroenterology and Motility, BIO-25, a multispecies probiotic, did not significantly modify the composition of the fecal microbiota, but interestingly, patients with specific basal features of the intestinal microbial ecosystem improved with treatment. Based on these data, it is tantalizing to speculate that microbiota composition serves as a predictor of the response to probiotic intervention. This mini-review addresses unresolved issues related to mechanisms through which probiotics may exert their beneficial effects, the biological, as well as clinical predictors of favorable outcomes in IBS and finally considers possible new directions for future studies.}, }
@article {pmid30459400, year = {2018}, author = {Chen, B and Zhao, Y and Li, S and Yang, L and Wang, H and Wang, T and Bin Shi,  and Gai, Z and Heng, X and Zhang, C and Yang, J and Zhang, L}, title = {Variations in oral microbiome profiles in rheumatoid arthritis and osteoarthritis with potential biomarkers for arthritis screening.}, journal = {Scientific reports}, volume = {8}, number = {1}, pages = {17126}, pmid = {30459400}, issn = {2045-2322}, support = {No. 31471202//National Natural Science Foundation of China (National Science Foundation of China)/International ; }, mesh = {Adult ; Aged ; Arthritis, Rheumatoid/*microbiology ; Biomarkers/analysis ; Case-Control Studies ; Female ; Humans ; Male ; Microbiota/genetics/*physiology ; Middle Aged ; Osteoarthritis/*microbiology ; RNA, Ribosomal, 16S ; Saliva/*microbiology ; }, abstract = {The key to arthritis management is early diagnosis and treatment to prevent further joint destruction and maximize functional ability. Osteoarthritis (OA) and rheumatoid arthritis (RA) are two common types of arthritis that the primary care provider must differentiate, in terms of diagnosis and treatment. Effective and non-invasive strategies for early detection and disease identification are sorely needed. Growing evidence suggests that RA has a correlation with oral microbiome and may be affected by its dynamic variations. There is already a study comparing oral microbiome in patients with RA and OA, however, it did not screen for potential biomarkers for arthritis. In this study, we assessed the oral microbiome in saliva samples from 110 RA patients, 67 OA patients and 155 healthy subjects, using 16S rRNA gene amplicon sequencing. The structure and differences in oral microbiome between RA, OA and healthy subjects were analyzed. Eight oral bacterial biomarkers were identified to differentiate RA from OA. This report provides proof of oral microbiota as an informative source for discovering non-invasive biomarkers for arthritis screening.}, }
@article {pmid30452039, year = {2019}, author = {Rajakovich, LJ and Balskus, EP}, title = {Metabolic functions of the human gut microbiota: the role of metalloenzymes.}, journal = {Natural product reports}, volume = {36}, number = {4}, pages = {593-625}, pmid = {30452039}, issn = {1460-4752}, mesh = {Ammonia/metabolism ; Cresols/metabolism ; Enzymes/chemistry/*metabolism ; Gastrointestinal Microbiome/*physiology ; Host-Pathogen Interactions/immunology/*physiology ; Humans ; Hydrogen Sulfide/metabolism ; Metals/chemistry/metabolism ; Methylamines/metabolism ; Nucleoside Q/biosynthesis ; Polysaccharides/metabolism ; Vitamins/biosynthesis ; Xenobiotics/pharmacokinetics ; }, abstract = {Covering: up to the end of 2017 The human body is composed of an equal number of human and microbial cells. While the microbial community inhabiting the human gastrointestinal tract plays an essential role in host health, these organisms have also been connected to various diseases. Yet, the gut microbial functions that modulate host biology are not well established. In this review, we describe metabolic functions of the human gut microbiota that involve metalloenzymes. These activities enable gut microbial colonization, mediate interactions with the host, and impact human health and disease. We highlight cases in which enzyme characterization has advanced our understanding of the gut microbiota and examples that illustrate the diverse ways in which metalloenzymes facilitate both essential and unique functions of this community. Finally, we analyze Human Microbiome Project sequencing datasets to assess the distribution of a prominent family of metalloenzymes in human-associated microbial communities, guiding future enzyme characterization efforts.}, }
@article {pmid30449316, year = {2018}, author = {Guerin, E and Shkoporov, A and Stockdale, SR and Clooney, AG and Ryan, FJ and Sutton, TDS and Draper, LA and Gonzalez-Tortuero, E and Ross, RP and Hill, C}, title = {Biology and Taxonomy of crAss-like Bacteriophages, the Most Abundant Virus in the Human Gut.}, journal = {Cell host &amp; microbe}, volume = {24}, number = {5}, pages = {653-664.e6}, doi = {10.1016/j.chom.2018.10.002}, pmid = {30449316}, issn = {1934-6069}, mesh = {Bacteriophages/*classification/*genetics/*physiology/ultrastructure ; Base Sequence ; Capsid Proteins/genetics ; DNA Viruses ; Feces/virology ; Fermentation ; *Gastrointestinal Microbiome ; Genome, Viral/genetics ; Genomics ; Humans ; Metagenomics/methods ; *Phylogeny ; Sequence Analysis ; Viral Proteins/genetics ; }, abstract = {CrAssphages represent the most abundant virus in the human gut microbiota, but the lack of available genome sequences for comparison has kept them enigmatic. Recently, sequence-based classification of distantly related crAss-like phages from multiple environments was reported, leading to a proposed familial-level taxonomic group. Here, we assembled the metagenomic sequencing reads from 702 human fecal virome/phageome samples and analyzed 99 complete circular crAss-like phage genomes and 150 contigs ≥70 kb. In silico comparative genomics and taxonomic analysis enabled a classification scheme of crAss-like phages from human fecal microbiomes into four candidate subfamilies composed of ten candidate genera. Laboratory analysis was performed on fecal samples from an individual harboring seven distinct crAss-like phages. We achieved crAss-like phage propagation in ex vivo human fecal fermentations and visualized short-tailed podoviruses by electron microscopy. Mass spectrometry of a crAss-like phage capsid protein could be linked to metagenomic sequencing data, confirming crAss-like phage structural annotations.}, }
@article {pmid30443602, year = {2018}, author = {Hillmann, B and Al-Ghalith, GA and Shields-Cutler, RR and Zhu, Q and Gohl, DM and Beckman, KB and Knight, R and Knights, D}, title = {Evaluating the Information Content of Shallow Shotgun Metagenomics.}, journal = {mSystems}, volume = {3}, number = {6}, pages = {}, pmid = {30443602}, issn = {2379-5077}, support = {P01 DK078669/DK/NIDDK NIH HHS/United States ; R01 AI121383/AI/NIAID NIH HHS/United States ; }, abstract = {Although microbial communities are associated with human, environmental, plant, and animal health, there exists no cost-effective method for precisely characterizing species and genes in such communities. While deep whole-metagenome shotgun (WMS) sequencing provides high taxonomic and functional resolution, it is often prohibitively expensive for large-scale studies. The prevailing alternative, 16S rRNA gene amplicon (16S) sequencing, often does not resolve taxonomy past the genus level and provides only moderately accurate predictions of the functional profile; thus, there is currently no widely accepted approach to affordable, high-resolution, taxonomic, and functional microbiome analysis. To address this technology gap, we evaluated the information content of shallow shotgun sequencing with as low as 0.5 million sequences per sample as an alternative to 16S sequencing for large human microbiome studies. We describe a library preparation protocol enabling shallow shotgun sequencing at approximately the same per-sample cost as 16S sequencing. We analyzed multiple real and simulated biological data sets, including two novel human stool samples with ultradeep sequencing of 2.5 billion sequences per sample, and found that shallow shotgun sequencing recovers more-accurate species-level taxonomic and functional profiles of the human microbiome than 16S sequencing. We discuss the inherent limitations of shallow shotgun sequencing and note that 16S sequencing remains a valuable and important method for taxonomic profiling of novel environments. Although deep WMS sequencing remains the gold standard for high-resolution microbiome analysis, we recommend that researchers consider shallow shotgun sequencing as a useful alternative to 16S sequencing for large-scale human microbiome research studies where WMS sequencing may be cost-prohibitive. IMPORTANCE A common refrain in recent microbiome-related academic meetings is that the field needs to move away from broad taxonomic surveys using 16S sequencing and toward more powerful longitudinal studies using shotgun sequencing. However, performing deep shotgun sequencing in large longitudinal studies remains prohibitively expensive for all but the most well-funded research labs and consortia, which leads many researchers to choose 16S sequencing for large studies, followed by deep shotgun sequencing on a subset of targeted samples. Here, we show that shallow- or moderate-depth shotgun sequencing may be used by researchers to obtain species-level taxonomic and functional data at approximately the same cost as amplicon sequencing. While shallow shotgun sequencing is not intended to replace deep shotgun sequencing for strain-level characterization, we recommend that microbiome scientists consider using shallow shotgun sequencing instead of 16S sequencing for large-scale human microbiome studies.}, }
@article {pmid30439937, year = {2018}, author = {Jha, AR and Davenport, ER and Gautam, Y and Bhandari, D and Tandukar, S and Ng, KM and Fragiadakis, GK and Holmes, S and Gautam, GP and Leach, J and Sherchand, JB and Bustamante, CD and Sonnenburg, JL}, title = {Gut microbiome transition across a lifestyle gradient in Himalaya.}, journal = {PLoS biology}, volume = {16}, number = {11}, pages = {e2005396}, pmid = {30439937}, issn = {1545-7885}, support = {F32 DK109595/DK/NIDDK NIH HHS/United States ; R01 DK085025/DK/NIDDK NIH HHS/United States ; }, mesh = {Adult ; Bacteria/genetics ; Diet ; Diet, Paleolithic ; Feces/microbiology ; Female ; Gastrointestinal Microbiome/*genetics/physiology ; Genetics, Population/methods ; Geography ; Humans ; Life Style/*ethnology ; Male ; Microbiota/*genetics ; Middle Aged ; Nepal/ethnology ; RNA, Ribosomal, 16S/genetics ; Rural Population ; }, abstract = {The composition of the gut microbiome in industrialized populations differs from those living traditional lifestyles. However, it has been difficult to separate the contributions of human genetic and geographic factors from lifestyle. Whether shifts away from the foraging lifestyle that characterize much of humanity's past influence the gut microbiome, and to what degree, remains unclear. Here, we characterize the stool bacterial composition of four Himalayan populations to investigate how the gut community changes in response to shifts in traditional human lifestyles. These groups led seminomadic hunting-gathering lifestyles until transitioning to varying levels of agricultural dependence upon farming. The Tharu began farming 250-300 years ago, the Raute and Raji transitioned 30-40 years ago, and the Chepang retain many aspects of a foraging lifestyle. We assess the contributions of dietary and environmental factors on their gut-associated microbes and find that differences in the lifestyles of Himalayan foragers and farmers are strongly correlated with microbial community variation. Furthermore, the gut microbiomes of all four traditional Himalayan populations are distinct from that of the Americans, indicating that industrialization may further exacerbate differences in the gut community. The Chepang foragers harbor an elevated abundance of taxa associated with foragers around the world. Conversely, the gut microbiomes of the populations that have transitioned to farming are more similar to those of Americans, with agricultural dependence and several associated lifestyle and environmental factors correlating with the extent of microbiome divergence from the foraging population. The gut microbiomes of Raute and Raji reveal an intermediate state between the Chepang and Tharu, indicating that divergence from a stereotypical foraging microbiome can occur within a single generation. Our results also show that environmental factors such as drinking water source and solid cooking fuel are significantly associated with the gut microbiome. Despite the pronounced differences in gut bacterial composition across populations, we found little differences in alpha diversity across lifestyles. These findings in genetically similar populations living in the same geographical region establish the key role of lifestyle in determining human gut microbiome composition and point to the next challenging steps of determining how large-scale gut microbiome reconfiguration impacts human biology.}, }
@article {pmid30431239, year = {2019}, author = {Berry, D}, title = {Up-close-and-personal with the human microbiome.}, journal = {Environmental microbiology reports}, volume = {11}, number = {1}, pages = {17-19}, doi = {10.1111/1758-2229.12709}, pmid = {30431239}, issn = {1758-2229}, mesh = {Diet Therapy ; Drug Design ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/drug effects/genetics/*physiology ; Genomics ; Humans ; Microbiota/drug effects/genetics/*physiology ; Phage Therapy ; }, }
@article {pmid30426826, year = {2019}, author = {Daisley, BA and Monachese, M and Trinder, M and Bisanz, JE and Chmiel, JA and Burton, JP and Reid, G}, title = {Immobilization of cadmium and lead by Lactobacillus rhamnosus GR-1 mitigates apical-to-basolateral heavy metal translocation in a Caco-2 model of the intestinal epithelium.}, journal = {Gut microbes}, volume = {10}, number = {3}, pages = {321-333}, pmid = {30426826}, issn = {1949-0984}, mesh = {Adsorption ; Biological Transport ; Caco-2 Cells ; Cadmium/*metabolism/toxicity ; Cell Survival/drug effects ; Environmental Pollutants/*metabolism/toxicity ; Humans ; Intestinal Mucosa/drug effects/*metabolism ; Lacticaseibacillus rhamnosus/*metabolism ; Lead/*metabolism/toxicity ; Metals, Heavy/*metabolism/toxicity ; Probiotics/*metabolism/pharmacology ; }, abstract = {Heavy metals are highly toxic elements that contaminate the global food supply and affect human and wildlife health. Purification technologies are often too expensive or not practically applicable for large-scale implementation, especially in impoverished nations where heavy metal contamination is widespread. Lactobacillus rhamnosus GR-1 (LGR-1) was shown in previous work to reduce heavy metal bioaccumulation in a Tanzanian cohort of women and children through indeterminant mechanisms. Here, it was hypothesized that LGR-1 could sequester the heavy metals lead (Pb) and cadmium (Cd), thereby reducing their absorption across intestinal epithelium. LGR-1 and other lactobacilli significantly reduced the amount of Pb and Cd in solution at all concentrations tested (0.5 mg/L - 50 mg/L) and exhibited sustained binding profiles over a 48-hour period. Relative binding efficiency of LGR-1 decreased as Pb concentration increased, with an absolute minimum binding threshold apparent at concentrations of 2 mg/L and above. Electron microscopy revealed that Pb formed irregular cell-surface clusters on LGR-1, while Cd appeared to form intracellular polymeric clusters. Additionally, LGR-1 was able to significantly reduce apical-to-basolateral translocation of Pb and Cd in a Caco-2 model of the intestinal epithelium. These findings demonstrate the absorbent properties of LGR-1 can immobilize Pb and Cd, effectively reducing their translocation across the intestinal epithelium in vitro. Oral administration of heavy metal-binding Lactobacillus spp. (many of which are known human symbionts and strains of established probiotics) may offer a simple and effective means to reduce the amount of heavy metals absorbed from foods in contaminated regions of the world.}, }
@article {pmid30423063, year = {2018}, author = {Frioux, C and Fremy, E and Trottier, C and Siegel, A}, title = {Scalable and exhaustive screening of metabolic functions carried out by microbial consortia.}, journal = {Bioinformatics (Oxford, England)}, volume = {34}, number = {17}, pages = {i934-i943}, pmid = {30423063}, issn = {1367-4811}, mesh = {Humans ; *Microbial Consortia ; Microbiota ; Software ; }, abstract = {MOTIVATION: The selection of species exhibiting metabolic behaviors of interest is a challenging step when switching from the investigation of a large microbiota to the study of functions effectiveness. Approaches based on a compartmentalized framework are not scalable. The output of scalable approaches based on a non-compartmentalized modeling may be so large that it has neither been explored nor handled so far.<br><br>RESULTS: We present the Miscoto tool to facilitate the selection of a community optimizing a desired function in a microbiome by reporting several possibilities which can be then sorted according to biological criteria. Communities are exhaustively identified using logical programming and by combining the non-compartmentalized and the compartmentalized frameworks. The benchmarking of 4.9 million metabolic functions associated with the Human Microbiome Project, shows that Miscoto is suited to screen and classify metabolic producibility in terms of feasibility, functional redundancy and cooperation processes involved. As an illustration of a host-microbial system, screening the Recon 2.2 human metabolism highlights the role of different consortia within a family of 773 intestinal bacteria.<br><br>Miscoto source code, instructions for use and examples are available at: https://github.com/cfrioux/miscoto.}, }
@article {pmid30420594, year = {2018}, author = {Yost, S and Stashenko, P and Choi, Y and Kukuruzinska, M and Genco, CA and Salama, A and Weinberg, EO and Kramer, CD and Frias-Lopez, J}, title = {Increased virulence of the oral microbiome in oral squamous cell carcinoma revealed by metatranscriptome analyses.}, journal = {International journal of oral science}, volume = {10}, number = {4}, pages = {32}, pmid = {30420594}, issn = {2049-3169}, support = {R01 DE021553/DE/NIDCR NIH HHS/United States ; }, mesh = {Carcinoma, Squamous Cell/*microbiology ; Humans ; *Metagenome ; *Microbiota ; Mouth Neoplasms/*microbiology ; Phylogeny ; Pilot Projects ; RNA, Messenger/metabolism ; *Transcriptome ; Virulence ; Virulence Factors/*metabolism ; }, abstract = {Oral squamous cell carcinoma (OSCC) is the most prevalent and most commonly studied oral cancer. However, there is a void regarding the role that the oral microbiome may play in OSCC. Although the relationship between microbial community composition and OSCC has been thoroughly investigated, microbial profiles of the human microbiome in cancer are understudied. Here we performed a small pilot study of community-wide metatranscriptome analysis to profile mRNA expression in the entire oral microbiome in OSCC to reveal molecular functions associated with this disease. Fusobacteria showed a statistically significantly higher number of transcripts at tumour sites and tumour-adjacent sites of cancer patients compared to the healthy controls analysed. Regardless of the community composition, specific metabolic signatures were consistently found in disease. Activities such as iron ion transport, tryptophanase activity, peptidase activities and superoxide dismutase were over-represented in tumour and tumour-adjacent samples when compared to the healthy controls. The expression of putative virulence factors in the oral communities associated with OSCC showed that activities related to capsule biosynthesis, flagellum synthesis and assembly, chemotaxis, iron transport, haemolysins and adhesins were upregulated at tumour sites. Moreover, activities associated with protection against reactive nitrogen intermediates, chemotaxis, flagellar and capsule biosynthesis were also upregulated in non-tumour sites of cancer patients. Although they are preliminary, our results further suggest that Fusobacteria may be the leading phylogenetic group responsible for the increase in expression of virulence factors in the oral microbiome of OSCC patients.}, }
@article {pmid30419494, year = {2019}, author = {Ventura Spagnolo, E and Stassi, C and Mondello, C and Zerbo, S and Milone, L and Argo, A}, title = {Forensic microbiology applications: A systematic review.}, journal = {Legal medicine (Tokyo, Japan)}, volume = {36}, number = {}, pages = {73-80}, doi = {10.1016/j.legalmed.2018.11.002}, pmid = {30419494}, issn = {1873-4162}, mesh = {Adult ; Aged ; Body Fluids/*microbiology ; Brain/*microbiology ; Cause of Death ; Databases, Bibliographic ; Digestive System/*microbiology ; Female ; *Forensic Medicine ; Heart/*microbiology ; Humans ; Male ; *Microbiota ; Middle Aged ; *Postmortem Changes ; Skin/*microbiology ; Time Factors ; }, abstract = {According to the Human Microbiome Project (HMP), a healthy human body contains ten times more microbes than human cells. Microbial communities colonize different organs of the body, playing fundamental roles both in human health and disease. Despite the vast scientific knowledge of the role of microbial communities in a living body, little is known at present about microbial changes occurring after death, thus leading many authors to investigate the composition of the thanatomicrobiome and its potential applications in the forensic field. The aim of the following review is to provide a general overview of the advances of postmortem microbiology research, mainly focusing on the role of microbiological investigations carried out on internal organs and fluids. To this end, a total of 19 studies have been sistematically reviewed, each one chosen according to specific inclusion/exclusion criteria. The selected studies assess the contribution of contamination, postmortem transmigration and agonal spread to microbial isolation from dead body samples, and shed light on the role of postmortem microbiological investigations in several forensic fields, such as cause of death or PMI determination.}, }
@article {pmid30417656, year = {2018}, author = {Fonkou, MD and Dufour, JC and Dubourg, G and Raoult, D}, title = {Repertoire of bacterial species cultured from the human oral cavity and respiratory tract.}, journal = {Future microbiology}, volume = {13}, number = {}, pages = {1611-1624}, doi = {10.2217/fmb-2018-0181}, pmid = {30417656}, issn = {1746-0921}, mesh = {Bacteria/*genetics/*pathogenicity ; Bronchoalveolar Lavage Fluid/microbiology ; Cell Culture Techniques ; High-Throughput Nucleotide Sequencing ; Humans ; Lung/microbiology ; MEDLINE ; Microbiota/*genetics ; Mouth/*microbiology ; Respiratory System/*microbiology ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization ; Sputum/microbiology ; Virulence/genetics ; }, abstract = {While the gut microbiota is currently in the spotlight, the airway microbiome has been recently associated with several pulmonary diseases and carcinogenesis. As there are several biases associated with high-throughput sequencing methods, cultivation techniques are crucial for the investigation of the human microbiome. We thus aimed to build an exhaustive database, including a list of microbes isolated by culture from respiratory specimens, by performing a review of the literature. Herein, we have listed a total of 756 species cultured from the human respiratory tract. This represents 27.23% of the overall bacterial richness captured from human being by culture methods. This repertoire could be valuable for the elucidation of the interactions between the respiratory microbiome and human health.}, }
@article {pmid30401779, year = {2018}, author = {Bratburd, JR and Keller, C and Vivas, E and Gemperline, E and Li, L and Rey, FE and Currie, CR}, title = {Gut Microbial and Metabolic Responses to Salmonella enterica Serovar Typhimurium and Candida albicans.}, journal = {mBio}, volume = {9}, number = {6}, pages = {}, pmid = {30401779}, issn = {2150-7511}, support = {U19 AI109673/AI/NIAID NIH HHS/United States ; R56 DK071801/DK/NIDDK NIH HHS/United States ; R01 DK108259/DK/NIDDK NIH HHS/United States ; S10 RR029531/RR/NCRR NIH HHS/United States ; T32 AI055397/AI/NIAID NIH HHS/United States ; R01 DK071801/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Biosynthetic Pathways ; Candida albicans/pathogenicity ; Candidiasis/*microbiology ; Cecum/microbiology ; Disease Models, Animal ; Enterobacteriaceae/isolation &amp; purification ; *Gastrointestinal Microbiome ; Germ-Free Life ; Humans ; Male ; Metabolomics ; Metagenomics ; Mice ; Mice, Inbred C57BL ; *Microbiota ; Oxidative Stress ; Salmonella Infections, Animal/*microbiology ; Salmonella typhimurium/pathogenicity ; }, abstract = {The gut microbiota confers resistance to pathogens of the intestinal ecosystem, yet the dynamics of pathogen-microbiome interactions and the metabolites involved in this process remain largely unknown. Here, we use gnotobiotic mice infected with the virulent pathogen Salmonella enterica serovar Typhimurium or the opportunistic pathogen Candida albicans in combination with metagenomics and discovery metabolomics to identify changes in the community and metabolome during infection. To isolate the role of the microbiota in response to pathogens, we compared mice monocolonized with the pathogen, uninfected mice "humanized" with a synthetic human microbiome, or infected humanized mice. In Salmonella-infected mice, by 3 days into infection, microbiome community structure and function changed substantially, with a rise in Enterobacteriaceae strains and a reduction in biosynthetic gene cluster potential. In contrast, Candida-infected mice had few microbiome changes. The LC-MS metabolomic fingerprint of the cecum differed between mice monocolonized with either pathogen and humanized infected mice. Specifically, we identified an increase in glutathione disulfide, glutathione cysteine disulfide, inosine 5'-monophosphate, and hydroxybutyrylcarnitine in mice infected with Salmonella in contrast to uninfected mice and mice monocolonized with Salmonella These metabolites potentially play a role in pathogen-induced oxidative stress. These results provide insight into how the microbiota community members interact with each other and with pathogens on a metabolic level.IMPORTANCE The gut microbiota is increasingly recognized for playing a critical role in human health and disease, especially in conferring resistance to both virulent pathogens such as Salmonella, which infects 1.2 million people in the United States every year (E. Scallan, R. M. Hoekstra, F. J. Angulo, R. V. Tauxe, et al., Emerg Infect Dis 17:7-15, 2011, https://doi.org/10.3201/eid1701.P11101), and opportunistic pathogens like Candida, which causes an estimated 46,000 cases of invasive candidiasis each year in the United States (Centers for Disease Control and Prevention, Antibiotic Resistance Threats in the United States, 2013, 2013). Using a gnotobiotic mouse model, we investigate potential changes in gut microbial community structure and function during infection using metagenomics and metabolomics. We observe that changes in the community and in biosynthetic gene cluster potential occur within 3 days for the virulent Salmonella enterica serovar Typhimurium, but there are minimal changes with a poorly colonizing Candida albicans In addition, the metabolome shifts depending on infection status, including changes in glutathione metabolites in response to Salmonella infection, potentially in response to host oxidative stress.}, }
@article {pmid30400268, year = {2018}, author = {Ojo-Okunola, A and Nicol, M and du Toit, E}, title = {Human Breast Milk Bacteriome in Health and Disease.}, journal = {Nutrients}, volume = {10}, number = {11}, pages = {}, pmid = {30400268}, issn = {2072-6643}, support = {U01 AI110466/AI/NIAID NIH HHS/United States ; 1U01AI110466-01A1//H3Africa U01 AWARD FROM THE NATIONAL INSTITUTES OF HEALTH OF THE USA/ ; U54HG009824//NIH Office of the Director/ ; OPP1017641; OPP1017579//Bill and Melinda Gates Foundation/ ; U54 HG009824/HG/NHGRI NIH HHS/United States ; }, mesh = {Bacteria/isolation &amp; purification ; Feces/microbiology ; Female ; HIV Infections/microbiology/therapy ; Humans ; Infant ; Mastitis/microbiology/therapy ; *Microbiota ; Milk, Human/*microbiology ; Neoplasms/microbiology/therapy ; }, abstract = {It is well-known that, beyond nutritional components, human breast milk (HBM) contains a wide variety of non-nutritive bio-factors perfectly suited for the growing infant. In the pre-2000 era, HBM was considered sterile and devoid of micro-organisms. Though HBM was not included as part of the human microbiome project launched in 2007, great strides have been made in studying the bacterial diversity of HBM in both a healthy state and diseased state, and in understanding their role in infant health. HBM provides a vast array of beneficial micro-organisms that play a key role in colonizing the infant's mucosal system, including that of the gut. They also have a role in priming the infant's immune system and supporting its maturation. In this review, we provide an in-depth and updated insight into the immunomodulatory, metabolic, and anti-infective role of HBM bacteriome (bacterial community) and its effect on infant health. We also provide key information from the literature by exploring the possible origin of microbial communities in HBM, the bacterial diversity in this niche and the determinants influencing the HBM bacteriome. Lastly, we investigate the role of the HBM bacteriome in maternal infectious disease (human immunodeficiency virus (HIV) and mastitis)), and cancer. Key gaps in HBM bacterial research are also identified.}, }
@article {pmid32055558, year = {2018}, author = {Yang, J and Kim, EK and McDowell, A and Kim, YK}, title = {Microbe-derived extracellular vesicles as a smart drug delivery system.}, journal = {Translational and clinical pharmacology}, volume = {26}, number = {3}, pages = {103-110}, pmid = {32055558}, issn = {2383-5427}, abstract = {The human microbiome is known to play an essential role in influencing host health. Extracellular vesicles (EVs) have also been reported to act on a variety of signaling pathways, distally transport cellular components such as proteins, lipids, and nucleic acid, and have immunomodulatory effects. Here we shall review the current understanding of the intersectionality of the human microbiome and EVs in the emerging field of microbiota-derived EVs and their pharmacological potential. Microbes secrete several classes of EVs: outer membrane vesicles (OMVs), membrane vesicles (MVs), and apoptotic bodies. EV biogenesis is unique to each cell and regulated by sophisticated signaling pathways. EVs are primarily composed of lipids, proteins, nucleic acids, and recent evidence suggests they may also carry metabolites. These components interact with host cells and control various cellular processes by transferring their constituents. The pharmacological potential of microbiomederived EVs as vaccine candidates, biomarkers, and a smart drug delivery system is a promising area of future research. Therefore, it is necessary to elucidate in detail the mechanisms of microbiome-derived EV action in host health in a multi-disciplinary manner.}, }
@article {pmid33149747, year = {2018}, author = {Vlasova, AN and Rajashekara, G and Saif, LJ}, title = {Interactions between human microbiome, diet, enteric viruses and immune system: Novel insights from gnotobiotic pig research.}, journal = {Drug discovery today. Disease models}, volume = {28}, number = {}, pages = {95-103}, pmid = {33149747}, issn = {1740-6757}, abstract = {Studies over the past few decades demonstrated that gnotobiotic (Gn) pigs provide an unprecedented translational model to study human intestinal health and diseases. Due to the high degree of anatomical, physiological, metabolic, immunological, and developmental similarity, the domestic pig closely mimics the human intestinal microenvironment. Also, Gn piglets can be efficiently transplanted with human microbiota from infants, children and adults with resultant microbial profiles remarkably similar to the original human samples, a feat consistently not achievable in rodent models. Finally, Gn and human microbiota-associated (HMA) piglets are susceptible to human enteric viral pathogens (including human rotavirus, HRV) and can be fed authentic human diets, which further increases the translational potential of these models. In this review, we will focus on recent studies that evaluated the pathophysiology of protein malnutrition and the associated dysbiosis and immunological dysfunction in neonatal HMA piglets. Additionally, we will discuss studies of potential dietary interventions that moderate the effects of malnutrition and dysbiosis on antiviral immunity and HRV vaccines in HMA pigs. Such studies provide novel models and novel mechanistic insights critical for development of drug interventions.}, }
@article {pmid32337052, year = {2018}, author = {Shaw, LP and Sugden, NC}, title = {Portable sequencing, genomic data, and scale in global emerging infectious disease surveillance.}, journal = {Geo : geography and environment}, volume = {5}, number = {2}, pages = {e00066}, pmid = {32337052}, issn = {2054-4049}, abstract = {Emerging infectious diseases (EIDs) occur when pathogens unpredictably spread into new contexts. EID surveillance systems seek to rapidly identify EID outbreaks to contain spread and improve public health outcomes. Sequencing data has historically not been integrated into real-time responses, but portable DNA sequencing technology has prompted optimism among epidemiologists. Specifically, attention has focused on the goal of a "sequencing singularity": the integration of portable sequencers in a worldwide event-based surveillance network with other digital data (Gardy &amp; Loman, Nature Reviews Genetics, 19, 2018, p. 9). The sequencing singularity vision is a powerful socio-technical imaginary, shaping the discourse around the future of portable sequencing. Ethical and practical issues are bound by the vision in two ways: they are framed only as obstacles, and they are formulated only at the scales made visible by its implicit geography. This geography privileges two extremes of scale - the genomic and the global - and leaves intermediate scales comparatively unmapped. We explore how widespread portable sequencing could challenge this geography. Portable sequencers put the ability to produce genomic data in the hands of the individual. The explicit assertion of rights over data may therefore become a matter disputed more at an interpersonal scale than an international one. Portable sequencers also promise ubiquitous, indiscriminate sequencing of the total metagenomic content of samples, raising the question of what (or who) is under surveillance and inviting consideration of the human microbiome and more-than-human geographies. We call into question a conception of a globally integrated stream of sequencing data as composed mostly of "noise," within which signals of pathogen "emergence" are "hidden," considering it instead from the perspective of recent work into more-than-human geographies. Our work highlights a practical need for researchers to consider both the alternative possibilities they foreclose as well as the exciting opportunities they move towards when they deploy their visions of the future.}, }
@article {pmid30848142, year = {2018}, author = {Buchta, V}, title = {Vaginal microbiome.}, journal = {Ceska gynekologie}, volume = {83}, number = {5}, pages = {371-379}, pmid = {30848142}, issn = {1210-7832}, mesh = {Female ; Humans ; Lactic Acid/*metabolism ; *Lactobacillus ; *Microbiota ; Vagina/*microbiology ; Vaginosis, Bacterial/*microbiology ; }, abstract = {OBJECTIVE: Presentation of complex information about the vaginal microbiota from historical view to current concepts with focus on latest findings on the structure and functioning of the vaginal microbiome.<br><br>DESIGN: Review article.<br><br>SETTING: Department of Clinical Microbiology, University Hospital and Faculty of Medicine in Hradci Kr&#xe1;lov&#xe9;, Charles University in Prague.<br><br>METHODS: Literature review using the databases (PubMed, Web of Science, Ovid, etc.) with keywords (vaginal microbiota/ microbiom; vaginal discharge; bacterial vaginosis; vulvovaginitis; vaginal Lactobacillus).<br><br>RESULTS: The vaginal microbiome is a specific compartment of the human microbiome. Unique conditions of the vagina are characterized by a few microbial species, usually lactobacilli, which are able to utilize glycogen, which is under control of estrogens. Lactobacilli and other fermentative bacteria together with vaginal epithelial cells produce lactic acid and are responsible for acidifying vaginal milieu. Lactic acid occurs in two isomeric forms, and their relative ratio is likely to give the vaginal microbiota a certain degree of stability and ability to withstand some infections. This microbiota is manifested by a low degree of diversity and by the high dynamics of changes of its composition under the influence of various exogenous and endogenous factors. Increase in diversity can be paradoxically associated with a dysbiosis such as bacterial vaginosis. Individual species of lactobacilli mainly Lactobacillus crispatus characterize the main community state types in the vagina. Apart from lactobacilli, healthy women may be colonized with a non-lactobacillary microbiota whose rate is dependent on ethnicity.<br><br>CONCLUSION: The definition of vaginal microbiota cannot be only related to the presence or absence of individual microorganisms, although the incidence of some of them can be correlated with dysbiosis or eubiosis. The composition of microbiota is important, but it is only one of the basic attributes of normal vaginal microbiota, but not sufficient; that is the functional definition of vaginal microbiota in relation to its structure and dynamics, including the influence of ethnicity, physiological status of the vagina, and genetic disposition of woman.}, }
@article {pmid30815546, year = {2018}, author = {Wang, Z and Saha, S and Van Horn, S and Thomas, E and Traini, C and Sathe, G and Rajpal, DK and Brown, JR}, title = {Gut microbiome differences between metformin- and liraglutide-treated T2DM subjects.}, journal = {Endocrinology, diabetes &amp; metabolism}, volume = {1}, number = {1}, pages = {e00009}, pmid = {30815546}, issn = {2398-9238}, abstract = {INTRODUCTION: Metformin and glucagon-like peptide-1 (GLP-1) agonists are widely used for treating type two diabetes mellitus (T2DM). While recent studies suggest these drugs might modify the gastrointestinal tract (GIT) microbiome, further confirmation is required from human clinical trials.<br><br>MATERIALS AND METHODS: Here, we compare, in patients with T2DM, the effects of metformin (n&#xa0;=&#xa0;18 subjects) and liraglutide (n&#xa0;=&#xa0;19), a GLP-1 agonist, on their GIT microbiomes over a 42&#xa0;day period (n&#xa0;=&#xa0;74 samples) using 16S ribosomal RNA (rRNA) sequencing.<br><br>RESULTS: We found that these drugs had markedly different effects on the microbiome composition. At both baseline and Day 42, subjects taking metformin had a significant increase (Baseline adj. P&#xa0;=&#xa0;.038, Day 42 adj. P&#xa0;=&#xa0;.041) in the relative abundance of the bacterial genus Sutterella, whereas liraglutide dosing is associated with a significant increase (Baseline adj. P&#xa0;=&#xa0;.048, Day 42 adj. P&#xa0;=&#xa0;.003) in the genus Akkermansia, a GIT bacteria positively associated with gut barrier homoeostasis. Bacteroides and Akkermansia relative abundances were also significantly associated with duration of subject diabetes (adj P&#xa0;<&#xa0;.05). Specifically, there was a significantly higher abundance of Akkermansia in subjects with short and medium durations than those with long duration of diabetes.<br><br>DISCUSSION: To our knowledge, this is the first report of GLP-1 agonist-associated changes in the human microbiome and its differentiating effects to metformin. Our study suggests that modulation of the GIT microbiome is a potentially important component in the mechanism of action of these drugs.}, }
@article {pmid33525772, year = {2017}, author = {Shaw, LP and Smith, AM and Roberts, AP}, title = {The oral microbiome.}, journal = {Emerging topics in life sciences}, volume = {1}, number = {4}, pages = {287-296}, doi = {10.1042/ETLS20170040}, pmid = {33525772}, issn = {2397-8554}, abstract = {The human microbiome is receiving a great deal of attention as its role in health and disease becomes ever more apparent. The oral microbiome, perhaps due to the ease with which we can obtain samples, is arguably the most well-studied human microbiome to date. It is obvious, however, that we have only just begun to scratch the surface of the complex bacterial and bacterial-host interactions within this complex community. Here, we describe the factors which are known to influence the development of the seemingly globally conserved, core, oral microbiome and those which are likely to be responsible for the observed differences at the individual level. We discuss the paradoxical situation of maintaining a stable core microbiome which is at the same time incredibly resilient and adaptable to many different stresses encountered in the open environment of the oral cavity. Finally, we explore the interactions of the oral microbiome with the host and discuss the interactions underlying human health and disease.}, }
@article {pmid33525771, year = {2017}, author = {Kolmeder, CA}, title = {Proteomics and the human microbiome: where we are today and where we would like to be.}, journal = {Emerging topics in life sciences}, volume = {1}, number = {4}, pages = {401-409}, doi = {10.1042/ETLS20170051}, pmid = {33525771}, issn = {2397-8554}, abstract = {What are all these hundreds of different bacterial species doing in and on us? What interactions occur between the host and the microbes, and between the microbes themselves? By studying proteins, metaproteomics tries to find preliminary answers to these questions. There is daunting complexity around this; in fact, many of these proteins have never been studied before. This article is an introduction to the field of metaproteomics in the context of the human microbiome. It summarizes where we are and what we have learnt so far. The focus will be on faecal proteomics as most metaproteomics research has been conducted on that sample type. Metaproteomics has made major advances in the past decade, but new sample preparation strategies, improved mass spectrometric analysis and, most importantly, data analysis and interpretation have the potential to pave the way for large-cohort metaproteomics.}, }
@article {pmid33603248, year = {2015}, author = {Homburger, SA and Drits-Esser, D and Malone, M and Stark, LA}, title = {Microbes As Friends, Not Foes: Shifting the Focus from Pathogenesis to Symbiosis.}, journal = {The American biology teacher}, volume = {77}, number = {9}, pages = {659-668}, pmid = {33603248}, issn = {0002-7685}, support = {R25 AI095212/AI/NIAID NIH HHS/United States ; }, abstract = {Until about two decades ago, the standard method of studying a microbe was to isolate it, grow it in culture, stain it, and examine it under a microscope. Today, new genomic tools are helping expand our view of the microbial world. Instead of viewing them as "germs" to be eliminated, we are beginning to perceive our microbes as an extension of ourselves - an important organ with unique functions essential to our well-being. Scientists even came up with a new term, "microbiome," to define our microbes' genes as an important counterpart to our human genome. With new information about the human microbiome comes the challenge of shifting biology students' focus from casting microbes as pathogens toward appreciating microbes as symbionts. "The Human Microbiome," a curriculum supplement produced by the Genetic Science Learning Center, emphasizes that microbes living in and on our bodies perform neutral and beneficial functions, that human microbiota form thriving ecosystems, and that disruptions to our microbial ecosystems may have consequences. In this article, we describe the curriculum materials, provide strategies for incorporating this cutting-edge topic into biology classrooms, list connections to the Next Generation Science Standards, and report on recent research testing the curriculum supplement's effectiveness for student learning.}, }
@article {pmid30397357, year = {2018}, author = {Tirosh, O and Conlan, S and Deming, C and Lee-Lin, SQ and Huang, X and ,  and Su, HC and Freeman, AF and Segre, JA and Kong, HH}, title = {Expanded skin virome in DOCK8-deficient patients.}, journal = {Nature medicine}, volume = {24}, number = {12}, pages = {1815-1821}, pmid = {30397357}, issn = {1546-170X}, support = {Z01 HG000180-08//Intramural NIH HHS/United States ; ZIA AI001193-04//Intramural NIH HHS/United States ; ZIA BC010938-10//Intramural NIH HHS/United States ; }, mesh = {Adolescent ; Bacteriophages/genetics ; Child ; Female ; Genome, Viral/genetics ; Guanine Nucleotide Exchange Factors/deficiency/*genetics ; Healthy Volunteers ; Host Microbial Interactions/genetics/immunology ; Humans ; Immunity/genetics ; Immunologic Deficiency Syndromes/microbiology/pathology/*virology ; Lymphocytes/virology ; Male ; Metagenome/genetics/immunology ; Microbiota/genetics ; Papillomaviridae/isolation &amp; purification/pathogenicity ; Skin/microbiology/*virology ; Skin Diseases/genetics/microbiology/pathology/*virology ; }, abstract = {Human microbiome studies have revealed the intricate interplay of host immunity and bacterial communities to achieve homeostatic balance. Healthy skin microbial communities are dominated by bacteria with low viral representation[1-3], mainly bacteriophage. Specific eukaryotic viruses have been implicated in both common and rare skin diseases, but cataloging skin viral communities has been limited. Alterations in host immunity provide an opportunity to expand our understanding of microbial-host interactions. Primary immunodeficient patients manifest with various viral, bacterial, fungal, and parasitic infections, including skin infections[4]. Dedicator of cytokinesis 8 (DOCK8) deficiency is a rare primary human immunodeficiency characterized by recurrent cutaneous and systemic infections, as well as atopy and cancer susceptibility[5]. DOCK8, encoding a guanine nucleotide exchange factor highly expressed in lymphocytes, regulates actin cytoskeleton, which is critical for migration through collagen-dense tissues such as skin[6]. Analyzing deep metagenomic sequencing data from DOCK8-deficient skin samples demonstrated a notable increase in eukaryotic viral representation and diversity compared with healthy volunteers. De novo assembly approaches identified hundreds of novel human papillomavirus genomes, illuminating microbial dark matter. Expansion of the skin virome in DOCK8-deficient patients underscores the importance of immune surveillance in controlling eukaryotic viral colonization and infection.}, }
@article {pmid30396009, year = {2019}, author = {Woerner, AE and Novroski, NMM and Wendt, FR and Ambers, A and Wiley, R and Schmedes, SE and Budowle, B}, title = {Forensic human identification with targeted microbiome markers using nearest neighbor classification.}, journal = {Forensic science international. Genetics}, volume = {38}, number = {}, pages = {130-139}, doi = {10.1016/j.fsigen.2018.10.003}, pmid = {30396009}, issn = {1878-0326}, mesh = {Biodiversity ; Forensic Genetics/methods ; High-Throughput Nucleotide Sequencing ; Humans ; *Microbiota ; Phylogeny ; Sequence Analysis, DNA ; Skin/*microbiology ; }, abstract = {From the perspective of forensics genetics, the human microbiome is a rich, relatively untapped resource for human identity testing. Since it varies within and among people, and perhaps temporally, the potential forensic applications of the use of the microbiome can exceed that of human identification. However, the same inherent variability in microbial distributions may pose a substantial barrier to forming predictions on an individual as the source of the microbial sample unless stable signatures of the microbiome are identified and targeted. One of the more commonly adopted strategies for microbial human identification relies on quantifying which taxa are present and their respective abundance levels. It remains an open question if such microbial signatures are more individualizing than estimates of the degree of genetic relatedness between microbial samples. This study attempts to address this question by contrasting two prediction strategies. The first approach uses phylogenetic distance to predict the host individual; thus it operates under the premise that microbes within individuals are more closely related than microbes between/among individuals. The second approach uses population genetic measures of diversity at clade-specific markers, serving as a fine-grained assessment of microbial composition and quantification. Both assessments were performed using targeted sequencing of 286 markers from 22 microbial taxa sampled in 51 individuals across three body sites measured in triplicate. Nearest neighbor and reverse nearest neighbor classifiers were constructed based on the pooled data and yielded 71% and 78% accuracy, respectively, when diversity was considered, and performed significantly worse when a phylogenetic distance was used (54% and 63% accuracy, respectively). However, empirical estimates of classification accuracy were 100% when conditioned on a maximum nearest neighbor distance when diversity was used, while identification based on a phylogenetic distance failed to reach saturation. These findings suggest that microbial strain composition is more individualizing than that of a phylogeny, perhaps indicating that microbial composition may be more individualizing than recent common ancestry. One inference that may be drawn from these findings is that host-environment interactions may maintain the targeted microbial profile and that this maintenance may not necessarily be repopulated by intra-individual microbial strains.}, }
@article {pmid30392721, year = {2018}, author = {Cogdill, AP and Gaudreau, PO and Arora, R and Gopalakrishnan, V and Wargo, JA}, title = {The Impact of Intratumoral and Gastrointestinal Microbiota on Systemic Cancer Therapy.}, journal = {Trends in immunology}, volume = {39}, number = {11}, pages = {900-920}, doi = {10.1016/j.it.2018.09.007}, pmid = {30392721}, issn = {1471-4981}, support = {R01 CA219896/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Gastrointestinal Tract/*immunology/microbiology ; Homeostasis ; Host-Pathogen Interactions ; Humans ; Immunity ; Immunotherapy/*methods ; Mice ; Microbiota/*physiology ; Neoplasms/microbiology/*therapy ; Tumor Microenvironment ; }, abstract = {The human microbiome is a complex aggregate of microorganisms, and their genomes exert a number of influences crucial to the metabolic, immunologic, hormonal, and homeostatic function of the host. Recent work, both in preclinical mouse models and human studies, has shed light on the impact of gut and tumor microbiota on responses to systemic anticancer therapeutics. In light of this, strategies to target the microbiome to improve therapeutic responses are underway, including efforts to target gut and intratumoral microbes. Here, we discuss mechanisms by which microbiota may impact systemic and antitumor immunity, in addition to outstanding questions in the field. A deeper understanding of these is critical as we devise putative strategies to target the microbiome.}, }
@article {pmid30390805, year = {2018}, author = {Wang, Q and Yang, F and Jia, H}, title = {Mining the Microbiome for Drug Targets.}, journal = {Methods in enzymology}, volume = {610}, number = {}, pages = {59-72}, doi = {10.1016/bs.mie.2018.09.014}, pmid = {30390805}, issn = {1557-7988}, mesh = {Drug Discovery/*methods ; Humans ; Metagenome/drug effects ; Metagenomics/*methods ; Microbiota/*drug effects ; Molecular Targeted Therapy/methods ; }, abstract = {The human microbiome is our "other genome." Implicated in a growing list of complex diseases, for which genomic studies typically explain a portion of the disease susceptibility, the human gut microbiome has been at the spotlight for our understanding of human diseases. As the microbiome is intrinsically more variable than the human genome, it is important to take careful considerations at each step of a study. Here, we put forward our recommendations, which we envision would facilitate identification of true drug targets in the human microbiome in the colon as well as at other body sites.}, }
@article {pmid30390741, year = {2018}, author = {Wu, BG and Segal, LN}, title = {The Lung Microbiome and Its Role in Pneumonia.}, journal = {Clinics in chest medicine}, volume = {39}, number = {4}, pages = {677-689}, pmid = {30390741}, issn = {1557-8216}, support = {K23 AI102970/AI/NIAID NIH HHS/United States ; L30 AI138249/AI/NIAID NIH HHS/United States ; T32 CA193111/CA/NCI NIH HHS/United States ; UL1 TR001445/TR/NCATS NIH HHS/United States ; }, mesh = {Humans ; Inflammation/*complications/pathology ; Lung/*pathology ; Microbiota/*immunology ; Pneumonia/*microbiology ; }, abstract = {The use of next-generation sequencing and multiomic analysis reveals new insights on the identity of microbes in the lower airways blurring the lines between commensals and pathogens. Microbes are not found in isolation; rather they form complex metacommunities where microbe-host and microbe-microbe interactions play important roles on the host susceptibility to pathogens. In addition, the lower airway microbiota exert significant effects on host immune tone. Thus, this review highlights the roles that microbes in the respiratory tract play in the development of pneumonia.}, }
@article {pmid30389765, year = {2019}, author = {Junges, R and Sturød, K and Salvadori, G and Åmdal, HA and Chen, T and Petersen, FC}, title = {Characterization of a Signaling System in Streptococcus mitis That Mediates Interspecies Communication with Streptococcus pneumoniae.}, journal = {Applied and environmental microbiology}, volume = {85}, number = {2}, pages = {}, pmid = {30389765}, issn = {1098-5336}, mesh = {Bacterial Proteins/*genetics/metabolism ; Gene Expression Regulation, Bacterial/*physiology ; Quorum Sensing/*genetics ; Signal Transduction/*genetics ; Streptococcus mitis/*physiology ; Streptococcus pneumoniae/*physiology ; Trans-Activators/genetics/metabolism ; }, abstract = {Streptococcus mitis is found in the oral cavity and nasopharynx and forms a significant portion of the human microbiome. In this study, in silico analyses indicated the presence of an Rgg regulator and short hydrophobic peptide (Rgg/SHP) cell-to-cell communication system in S. mitis Although Rgg presented greater similarity to a repressor in Streptococcus pyogenes, autoinducing assays and genetic mutation analysis revealed that in S. mitis Rgg acts as an activator. Transcriptome analysis showed that in addition to shp, the system regulates two other downstream genes, comprising a segment of a putative lantibiotic gene cluster that is in a conjugative element locus in different members of the mitis group. Close comparison to a similar lantibiotic gene cluster in Streptococcus pneumoniae indicated that S. mitis lacked the full set of genes. Despite the potential of SHP to trigger a futile cycle of autoinduction, growth was not significantly affected for the rgg mutant under normal or antibiotic stress conditions. The S. mitis SHP was, however, fully functional in promoting cross-species communication and increasing S. pneumoniae surface polysaccharide production, which in this species is regulated by Rgg/SHP. The activity of SHPs produced by both species was detected in cocultures using a S. mitis reporter strain. In competitive assays, a slight advantage was observed for the rgg mutants. We conclude that the Rgg/SHP system in S. mitis regulates the expression of its own shp and activates an Rgg/SHP system in S. pneumoniae that regulates surface polysaccharide synthesis. Fundamentally, cross-communication of such systems may have a role during multispecies interactions.IMPORTANCE Bacteria secrete signal molecules into the environment which are sensed by other cells when the density reaches a certain threshold. In this study, we describe a communication system in Streptococcus mitis, a commensal species from the oral cavity, which we also found in several species and strains of streptococci from the mitis group. Further, we show that this system can promote cross-communication with S. pneumoniae, a closely related major human pathogen. Importantly, we show that this cross-communication can take place during coculture. While the genes regulated in S. mitis are likely part of a futile cycle of activation, the target genes in S. pneumoniae are potentially involved in virulence. The understanding of such complex communication networks can provide important insights into the dynamics of bacterial communities.}, }
@article {pmid30384329, year = {2018}, author = {Schooley, RT}, title = {The human microbiome: implications for health and disease, including HIV infection.}, journal = {Topics in antiviral medicine}, volume = {26}, number = {3}, pages = {75-78}, pmid = {30384329}, issn = {2161-5853}, mesh = {*Dysbiosis ; Female ; Gastrointestinal Microbiome ; HIV Infections/*complications ; Humans ; *Microbiota ; Vagina/microbiology ; Vaginosis, Bacterial ; }, abstract = {Our increased understanding of the human microbiome has brought insight into the role it plays in health and disease, including HIV infection. Studies have shown that the gut microbiome is less diverse in individuals with HIV infection than in noninfected control subjects. Efforts to modify the microbiome to bolster immune reconstitution in people with HIV infection have so far been unsuccessful. The vaginal microbiome affects risk of HIV acquisition, with Lactobacillus dominance being protective compared with vaginosis characterized by larger populations of Gardnerella. The vaginal microbiome might also affect efficacy of topical tenofovir disoproxil fumarate preexposure prophylaxis. This article summarizes a presentation by Robert T. Schooley, MD, at the IAS-USA continuing education program held in San Francisco in May 2018.}, }
@article {pmid30377376, year = {2018}, author = {Franzosa, EA and McIver, LJ and Rahnavard, G and Thompson, LR and Schirmer, M and Weingart, G and Lipson, KS and Knight, R and Caporaso, JG and Segata, N and Huttenhower, C}, title = {Species-level functional profiling of metagenomes and metatranscriptomes.}, journal = {Nature methods}, volume = {15}, number = {11}, pages = {962-968}, pmid = {30377376}, issn = {1548-7105}, support = {P30 DK043351/DK/NIDDK NIH HHS/United States ; U54 DE023798/DE/NIDCR NIH HHS/United States ; }, mesh = {Bacteria/*classification/*genetics/isolation &amp; purification ; Bacterial Proteins/*genetics/metabolism ; *Gene Expression Profiling ; High-Throughput Nucleotide Sequencing ; Humans ; *Metagenome ; Microbiota ; *Software ; Species Specificity ; *Transcriptome ; }, abstract = {Functional profiles of microbial communities are typically generated using comprehensive metagenomic or metatranscriptomic sequence read searches, which are time-consuming, prone to spurious mapping, and often limited to community-level quantification. We developed HUMAnN2, a tiered search strategy that enables fast, accurate, and species-resolved functional profiling of host-associated and environmental communities. HUMAnN2 identifies a community's known species, aligns reads to their pangenomes, performs translated search on unclassified reads, and finally quantifies gene families and pathways. Relative to pure translated search, HUMAnN2 is faster and produces more accurate gene family profiles. We applied HUMAnN2 to study clinal variation in marine metabolism, ecological contribution patterns among human microbiome pathways, variation in species' genomic versus transcriptional contributions, and strain profiling. Further, we introduce 'contributional diversity' to explain patterns of ecological assembly across different microbial community types.}, }
@article {pmid30374951, year = {2019}, author = {Vinberg, M and Ottesen, NM and Meluken, I and Sørensen, N and Pedersen, O and Kessing, LV and Miskowiak, KW}, title = {Remitted affective disorders and high familial risk of affective disorders associate with aberrant intestinal microbiota.}, journal = {Acta psychiatrica Scandinavica}, volume = {139}, number = {2}, pages = {174-184}, doi = {10.1111/acps.12976}, pmid = {30374951}, issn = {1600-0447}, support = {//H&#xf8;rslev Foundation/International ; //The Research fund of the Capital Region of Denmark/International ; //Axel Thomsens Foundation/International ; //Novo Nordisk Foundation/International ; R108-A10015//Lundbeck Foundation/International ; //(Laegevidenskabens fremme) Foundation/International ; //Augustinus Foundation/International ; }, mesh = {Adult ; Bipolar Disorder/genetics/psychology ; Classification/methods ; Denmark/epidemiology ; Diseases in Twins/genetics/psychology ; Female ; Gastrointestinal Microbiome/*genetics/physiology ; Genetic Predisposition to Disease ; Humans ; Male ; Middle Aged ; Mood Disorders/*complications/epidemiology/*genetics/psychology ; Remission Induction ; Risk ; Sequence Analysis, DNA/methods ; Twins, Monozygotic/*genetics/psychology ; }, abstract = {OBJECTIVE: Affective disorders seem associated with aberrant intestinal microbiota but whether this pattern also occurs in individuals at increased heritable risk is unknown. We investigated associations between gut microbiota profiles and affective disorders by comparing monozygotic (MZ) twins concordant (affected twins with unipolar or bipolar disorder in remission) and discordant to affective disorders (high-risk) with MZ twins without affective disorders (low-risk).<br><br>METHODS: Stool samples were collected from 128 MZ twins and the microbiome was profiled using 16S rDNA sequencing of the V3-V4 region.<br><br>RESULTS: Affected twins had a lower diversity and an absence of a specific operational taxonomical unit (OTU) in comparison with low-risk twins. The high-risk twins exhibited the same pattern although the lower diversity was only at a trend level. The OTU belonged to the family Christensenellaceae. The findings were not explained by lifestyle factors (smoking, alcohol consumption, body mass index, or psychotropic medication).<br><br>CONCLUSION: Affected twins in remission and high-risk twins presented aberrant gut microbiota with depletion of a specific OTU. If replicated, this reduced relative sequence absence may together with the globally altered microbiota composition act as a vulnerability marker by accentuating the effect of gene-environment interactions in individuals genetically disposed for an affective disorder.}, }
@article {pmid30374830, year = {2019}, author = {Pretzl, B and Sälzer, S and Ehmke, B and Schlagenhauf, U and Dannewitz, B and Dommisch, H and Eickholz, P and Jockel-Schneider, Y}, title = {Administration of systemic antibiotics during non-surgical periodontal therapy-a consensus report.}, journal = {Clinical oral investigations}, volume = {23}, number = {7}, pages = {3073-3085}, pmid = {30374830}, issn = {1436-3771}, support = {2.2-220.522-97/15_1//Commission for Young Scientists and Gender Equality, University of Wuerzburg/ ; 2.2-220.522-97/2015_1//IZKF/ ; }, mesh = {*Anti-Bacterial Agents/therapeutic use ; Combined Modality Therapy ; Consensus ; Dental Scaling ; Humans ; Middle Aged ; *Periodontitis/therapy ; }, abstract = {AIM: The aim of this meta-review was to evaluate whether there is a meaningful clinical benefit regarding the use of systemic adjunctive antibiotics in the treatment of patients with periodontitis. Additionally, a consensus regarding possible recommendations for future administration of antibiotics should be reached.<br><br>METHODS: A structured literature search was performed by two independent investigators focusing on systematic reviews (SR) covering adjunctive systemic antibiosis during non-surgical periodontal therapy. Additionally, recent randomized clinical trials (RCT, July 2015 to July 2017) were searched systematically to update the latest SR. Results were summarized and discussed in a plenary to reach a consensus.<br><br>RESULTS: Mostly, systematic reviews and RCTs showed a significant positive effect of adjunctive systematic antibiosis compared to controls. These positive effects gain clinical relevance in patients with severe periodontal disease aged 55&#xa0;years and younger.<br><br>CONCLUSION: Systemic antibiotics as an adjunct to non-surgical periodontal therapy should be sensibly administered and restrictively used. Only certain groups of periodontitis patients show a significant and clinically relevant benefit after intake of systemic antibiosis during periodontal therapy.<br><br>CLINICAL RELEVANCE: Avoiding antibiotic resistance and possible side effects on the human microbiome should be a focus of dentists and physicians. Thus, a sensible administration of antibiotics is mandatory. This manuscript suggests guidelines for a reasonable use.}, }
@article {pmid30367598, year = {2018}, author = {Shi, JY and Huang, H and Zhang, YN and Cao, JB and Yiu, SM}, title = {BMCMDA: a novel model for predicting human microbe-disease associations via binary matrix completion.}, journal = {BMC bioinformatics}, volume = {19}, number = {Suppl 9}, pages = {281}, pmid = {30367598}, issn = {1471-2105}, support = {R03 AA016008/AA/NIAAA NIH HHS/United States ; }, mesh = {*Algorithms ; *Bacteria ; Bacterial Physiological Phenomena ; Computational Biology/*methods ; *Disease ; Host-Pathogen Interactions ; Humans ; *Microbiota ; *Models, Biological ; Risk Factors ; }, abstract = {BACKGROUND: Human Microbiome Project reveals the significant mutualistic influence between human body and microbes living in it. Such an influence lead to an interesting phenomenon that many noninfectious diseases are closely associated with diverse microbes. However, the identification of microbe-noninfectious disease associations (MDAs) is still a challenging task, because of both the high cost and the limitation of microbe cultivation. Thus, there is a need to develop fast approaches to screen potential MDAs. The growing number of validated MDAs enables us to meet the demand in a new insight. Computational approaches, especially machine learning, are promising to predict MDA candidates rapidly among a large number of microbe-disease pairs with the advantage of no limitation on microbe cultivation. Nevertheless, a few computational efforts at predicting MDAs are made so far.<br><br>RESULTS: In this paper, grouping a set of MDAs into a binary MDA matrix, we propose a novel predictive approach (BMCMDA) based on Binary Matrix Completion to predict potential MDAs. The proposed BMCMDA assumes that the incomplete observed MDA matrix is the summation of a latent parameterizing matrix and a noising matrix. It also assumes that the independently occurring subscripts of observed entries in the MDA matrix follows a binomial model. Adopting a standard mean-zero Gaussian distribution for the nosing matrix, we model the relationship between the parameterizing matrix and the MDA matrix under the observed microbe-disease pairs as a probit regression. With the recovered parameterizing matrix, BMCMDA deduces how likely a microbe would be associated with a particular disease. In the experiment under leave-one-out cross-validation, it exhibits the inspiring performance (AUC&#x2009;=&#x2009;0.906, AUPR =0.526) and demonstrates its superiority by ~&#x2009;7% and ~&#x2009;5% improvements in terms of AUC and AUPR respectively in the comparison with the pioneering approach KATZHMDA.<br><br>CONCLUSIONS: Our BMCMDA provides an effective approach for predicting MDAs and can be also extended to other similar predicting tasks of binary relationship (e.g. protein-protein interaction, drug-target interaction).}, }
@article {pmid30356183, year = {2018}, author = {Vatanen, T and Franzosa, EA and Schwager, R and Tripathi, S and Arthur, TD and Vehik, K and Lernmark, &#xc5; and Hagopian, WA and Rewers, MJ and She, JX and Toppari, J and Ziegler, AG and Akolkar, B and Krischer, JP and Stewart, CJ and Ajami, NJ and Petrosino, JF and Gevers, D and Lähdesmäki, H and Vlamakis, H and Huttenhower, C and Xavier, RJ}, title = {The human gut microbiome in early-onset type 1 diabetes from the TEDDY study.}, journal = {Nature}, volume = {562}, number = {7728}, pages = {589-594}, pmid = {30356183}, issn = {1476-4687}, support = {U01 DK063821/DK/NIDDK NIH HHS/United States ; UC4 DK063863/DK/NIDDK NIH HHS/United States ; UL1 TR002535/TR/NCATS NIH HHS/United States ; UL1 TR001427/TR/NCATS NIH HHS/United States ; U01 DK063790/DK/NIDDK NIH HHS/United States ; UL1 TR001082/TR/NCATS NIH HHS/United States ; R24 DK110499/DK/NIDDK NIH HHS/United States ; UL1 TR000064/TR/NCATS NIH HHS/United States ; HHSN267200700014C/LM/NLM NIH HHS/United States ; U01 DK063836/DK/NIDDK NIH HHS/United States ; U01 DK063829/DK/NIDDK NIH HHS/United States ; U01 DK063865/DK/NIDDK NIH HHS/United States ; UC4 DK095300/DK/NIDDK NIH HHS/United States ; UC4 DK063861/DK/NIDDK NIH HHS/United States ; UC4 DK063829/DK/NIDDK NIH HHS/United States ; UC4 DK063821/DK/NIDDK NIH HHS/United States ; UC4 DK117483/DK/NIDDK NIH HHS/United States ; UC4 DK063836/DK/NIDDK NIH HHS/United States ; UC4 DK112243/DK/NIDDK NIH HHS/United States ; U54 DE023798/DE/NIDCR NIH HHS/United States ; U01 DK063861/DK/NIDDK NIH HHS/United States ; UC4 DK063865/DK/NIDDK NIH HHS/United States ; U01 DK063863/DK/NIDDK NIH HHS/United States ; UC4 DK106955/DK/NIDDK NIH HHS/United States ; UC4 DK100238/DK/NIDDK NIH HHS/United States ; }, mesh = {Age of Onset ; Animals ; Bifidobacterium/enzymology/genetics/isolation &amp; purification ; Breast Feeding ; Child, Preschool ; Diabetes Mellitus, Type 1/*epidemiology/genetics/*microbiology/prevention &amp; control ; Disease Models, Animal ; Fatty Acids, Volatile/pharmacology ; Feces/microbiology ; Female ; Gastrointestinal Microbiome/genetics/immunology/*physiology ; *Health Surveys ; Humans ; Infant ; Islets of Langerhans/immunology ; Longitudinal Studies ; Male ; Mice ; Milk, Human/immunology/microbiology ; Proteobacteria/enzymology/genetics/isolation &amp; purification ; White People ; }, abstract = {Type 1 diabetes (T1D) is an autoimmune disease that targets pancreatic islet beta cells and incorporates genetic and environmental factors[1], including complex genetic elements[2], patient exposures[3] and the gut microbiome[4]. Viral infections[5] and broader gut dysbioses[6] have been identified as potential causes or contributing factors; however, human studies have not yet identified microbial compositional or functional triggers that are predictive of islet autoimmunity or T1D. Here we analyse 10,913 metagenomes in stool samples from 783 mostly white, non-Hispanic children. The samples were collected monthly from three months of age until the clinical end point (islet autoimmunity or T1D) in the The Environmental Determinants of Diabetes in the Young (TEDDY) study, to characterize the natural history of the early gut microbiome in connection to islet autoimmunity, T1D diagnosis, and other common early life events such as antibiotic treatments and probiotics. The microbiomes of control children contained more genes that were related to fermentation and the biosynthesis of short-chain fatty acids, but these were not consistently associated with particular taxa across geographically diverse clinical centres, suggesting that microbial factors associated with T1D are taxonomically diffuse but functionally more coherent. When we investigated the broader establishment and development of the infant microbiome, both taxonomic and functional profiles were dynamic and highly individualized, and dominated in the first year of life by one of three largely exclusive Bifidobacterium species (B. bifidum, B. breve or B. longum) or by the phylum Proteobacteria. In particular, the strain-specific carriage of genes for the utilization of human milk oligosaccharide within a subset of B. longum was present specifically in breast-fed infants. These analyses of TEDDY gut metagenomes provide, to our knowledge, the largest and most detailed longitudinal functional profile of the developing gut microbiome in relation to islet autoimmunity, T1D and other early childhood events. Together with existing evidence from human cohorts[7,8] and a T1D mouse model[9], these data support the protective effects of short-chain fatty acids in early-onset human T1D.}, }
@article {pmid30355348, year = {2018}, author = {Tackmann, J and Arora, N and Schmidt, TSB and Rodrigues, JFM and von Mering, C}, title = {Ecologically informed microbial biomarkers and accurate classification of mixed and unmixed samples in an extensive cross-study of human body sites.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {192}, pmid = {30355348}, issn = {2049-2618}, mesh = {Bacteria/*classification/*genetics ; Biomarkers/analysis ; DNA, Bacterial/*genetics ; Genome, Bacterial/*genetics ; Human Body ; Humans ; Machine Learning ; Microbiota/*genetics ; }, abstract = {BACKGROUND: The identification of body site-specific microbial biomarkers and their use for classification tasks have promising applications in medicine, microbial ecology, and forensics. Previous studies have characterized site-specific microbiota and shown that sample origin can be accurately predicted by microbial content. However, these studies were usually restricted to single datasets with consistent experimental methods and conditions, as well as comparatively small sample numbers. The effects of study-specific biases and statistical power on classification performance and biomarker identification thus remain poorly understood. Furthermore, reliable detection in mixtures of different body sites or with noise from environmental contamination has rarely been investigated thus far. Finally, the impact of ecological associations between microbes on biomarker discovery was usually not considered in previous work.<br><br>RESULTS: Here we present the analysis of one of the largest cross-study sequencing datasets of microbial communities from human body sites (15,082 samples from 57 publicly available studies). We show that training a Random Forest Classifier on this aggregated dataset increases prediction performance for body sites by 35% compared to a single-study classifier. Using simulated datasets, we further demonstrate that the source of different microbial contributions in mixtures of different body sites or with soil can be detected starting at 1% of the total microbial community. We apply a biomarker selection method that excludes indirect environmental associations driven by microbe-microbe associations, yielding a parsimonious set of highly predictive taxa including novel biomarkers and excluding many previously reported taxa. We find a considerable fraction of unclassified biomarkers ("microbial dark matter") and observe that negatively associated taxa have a surprisingly high impact on classification performance. We further detect a significant enrichment of rod-shaped, motile, and sporulating taxa for feces biomarkers, consistent with a highly competitive environment.<br><br>CONCLUSIONS: Our machine learning model shows strong body site classification performance, both in single-source samples and mixtures, making it promising for tasks requiring high accuracy, such as forensic applications. We report a core set of ecologically informed biomarkers, inferred across a wide range of experimental protocols and conditions, providing the most concise, general, and least biased overview of body site-associated microbes to date.}, }
@article {pmid30352623, year = {2018}, author = {Benler, S and Cobián-Güemes, AG and McNair, K and Hung, SH and Levi, K and Edwards, R and Rohwer, F}, title = {A diversity-generating retroelement encoded by a globally ubiquitous Bacteroides phage.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {191}, pmid = {30352623}, issn = {2049-2618}, mesh = {Bacteroides/genetics/*virology ; Genome, Viral/*genetics ; Humans ; Metagenome/genetics ; Prophages/*genetics ; Retroelements/*genetics ; Viral Tail Proteins/*genetics ; }, abstract = {BACKGROUND: Diversity-generating retroelements (DGRs) are genetic cassettes that selectively mutate target genes to produce hypervariable proteins. First characterized in Bordetella bacteriophage BPP-1, the DGR creates a hypervariable phage tail fiber that enables host tropism switching. Subsequent surveys for DGRs conclude that the majority identified to date are bacterial or archaeal in origin. This work examines bacteriophage and bacterial genomes for novel phage-encoded DGRs.<br><br>RESULTS: This survey discovered 92 DGRs that were only found in phages exhibiting a temperate lifestyle. The majority of phage-encoded DGRs were identified as prophages in bacterial hosts from the phyla Bacteroidetes, Proteobacteria, and Firmicutes. Sequence reads from these previously unidentified prophages were present in viral metagenomes (viromes), indicating these prophages can produce functional viruses. Five phages possessed hypervariable proteins with structural similarity to the tail fiber of BPP-1, whereas the functions of the remaining DGR target proteins were unknown. A novel temperate phage that harbors a DGR cassette targeting a protein of unknown function was induced from Bacteroides dorei. This phage, here named Bacteroides dorei Hankyphage, lysogenizes 13 different Bacteroides species and was present in 34% and 21% of whole-community metagenomes and human-associated viromes, respectively.<br><br>CONCLUSIONS: Here, the number of known DGR-containing phages is increased from four to 92. All of these phages exhibit a temperate lifestyle, including a cosmopolitan human-associated phage. Targeted hypervariation by temperate phages may be a ubiquitous mechanism underlying phage-bacteria interaction in the human microbiome.}, }
@article {pmid30349509, year = {2018}, author = {Chaudhari, NM and Gautam, A and Gupta, VK and Kaur, G and Dutta, C and Paul, S}, title = {PanGFR-HM: A Dynamic Web Resource for Pan-Genomic and Functional Profiling of Human Microbiome With Comparative Features.}, journal = {Frontiers in microbiology}, volume = {9}, number = {}, pages = {2322}, pmid = {30349509}, issn = {1664-302X}, abstract = {The conglomerate of microorganisms inhabiting various body-sites of human, known as the human microbiome, is one of the key determinants of human health and disease. Comprehensive pan-genomic and functional analysis approach for human microbiome components can enrich our understanding about impact of microbiome on human health. By utilizing this approach we developed PanGFR-HM (http://www.bioinfo.iicb.res.in/pangfr-hm/) - a novel dynamic web-resource that integrates genomic and functional characteristics of 1293 complete microbial genomes available from Human Microbiome Project. The resource allows users to explore genomic/functional diversity and genome-based phylogenetic relationships between human associated microbial genomes, not provided by any other resource. The key features implemented here include pan-genome and functional analysis of organisms based on taxonomy or body-site, and comparative analysis between groups of organisms. The first feature can also identify probable gene-loss events and significantly over/under represented KEGG/COG categories within pan-genome. The unique second feature can perform comparative genomic, functional and pathways analysis between 4 groups of microbes. The dynamic nature of this resource enables users to define parameters for orthologous clustering and to select any set of organisms for analysis. As an application for comparative feature of PanGFR-HM, we performed a comparative analysis with 67 Lactobacillus genomes isolated from human gut, oral cavity and urogenital tract, and therefore characterized the body-site specific genes, enzymes and pathways. Altogether, PanGFR-HM, being unique in its content and functionality, is expected to provide a platform for microbiome-based comparative functional and evolutionary genomics.}, }
@article {pmid30349024, year = {2018}, author = {Chen, Z and Yeoh, YK and Hui, M and Wong, PY and Chan, MCW and Ip, M and Yu, J and Burk, RD and Chan, FKL and Chan, PKS}, title = {Diversity of macaque microbiota compared to the human counterparts.}, journal = {Scientific reports}, volume = {8}, number = {1}, pages = {15573}, pmid = {30349024}, issn = {2045-2322}, mesh = {Anal Canal/*microbiology ; Animals ; Cluster Analysis ; DNA, Bacterial/chemistry/genetics ; DNA, Ribosomal/chemistry/genetics ; Female ; Healthy Volunteers ; Humans ; Macaca mulatta ; *Microbiota ; Mouth/*microbiology ; Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; Vagina/*microbiology ; }, abstract = {Studies on the microbial communities in non-human primate hosts provide unique insights in both evolution and function of microbes related to human health and diseases. Using 16S rRNA gene amplicon profiling, we examined the oral, anal and vaginal microbiota in a group of non-captive rhesus macaques (N = 116) and compared the compositions with the healthy communities from Human Microbiome Project. The macaque microbiota was dominated by Bacteroidetes, Firmicutes and Proteobacteria; however, there were marked differences in phylotypes enriched across body sites indicative of strong niche specialization. Compared to human gut microbiota where Bacteroides predominately enriched, the surveyed macaque anal community exhibited increased abundance of Prevotella. In contrast to the conserved human vaginal microbiota extremely dominated by Lactobacillus, the macaque vaginal microbial composition was highly diverse while lactobacilli were rare. A constant decrease of the vaginal microbiota diversity was observed among macaque samples from juvenile, adult without tubectomy, and adult with tubectomy, with the most notable distinction being the enrichment of Halomonas in juvenile and Saccharofermentans in contracepted adults. Both macaque and human oral microbiota were colonized with three most common oral bacterial genera: Streptococcus, Haemophilus and Veillonella, and shared relatively conserved communities to each other. A number of bacteria related to human pathogens were consistently detected in macaques. The findings delineate the range of structure and diversity of microbial communities in a wild macaque population, and enable the application of macaque as an animal model for future characterization of microbes in transmission, genomics and function.}, }
@article {pmid30345704, year = {2018}, author = {Ponziani, FR and Putignani, L and Paroni Sterbini, F and Petito, V and Picca, A and Del Chierico, F and Reddel, S and Calvani, R and Marzetti, E and Sanguinetti, M and Gasbarrini, A and Pompili, M}, title = {Influence of hepatitis C virus eradication with direct-acting antivirals on the gut microbiota in patients with cirrhosis.}, journal = {Alimentary pharmacology &amp; therapeutics}, volume = {48}, number = {11-12}, pages = {1301-1311}, doi = {10.1111/apt.15004}, pmid = {30345704}, issn = {1365-2036}, mesh = {Aged ; Antiviral Agents/pharmacology/*therapeutic use ; Biomarkers/blood ; Chemokines/blood ; Cytokines/blood ; Female ; Gastrointestinal Microbiome/*drug effects/physiology ; Hepacivirus/drug effects/physiology ; Hepatitis C, Chronic/*blood/diagnosis/*drug therapy ; Humans ; Intestines/drug effects/microbiology ; Liver Cirrhosis/*blood/diagnosis/*drug therapy ; Longitudinal Studies ; Male ; Middle Aged ; Prospective Studies ; }, abstract = {BACKGROUND: The cure of hepatitis C virus (HCV) infection may contribute to the reduction of liver fibrosis progression and potentially influence the gut-liver axis.<br><br>AIM: To investigate the influence of HCV infection eradication with direct-acting antivirals (DAAs) on the gut microbiota composition as well as on intestinal and systemic inflammatory parameters in patients with cirrhosis.<br><br>METHODS: Consecutive patients with HCV-related cirrhosis receiving DAA treatment were included. The gut microbiota composition, intestinal permeability, and inflammation were assessed before treatment and after 1&#xa0;year. Clinical outcomes such as episodes of decompensation and markers of liver fibrosis were evaluated over a 2-year follow-up period.<br><br>RESULTS: The gut microbiota alpha diversity in cirrhotic patients, which was lower than that in healthy subjects, was significantly improved by the cure of HCV infection and a shift in the overall gut microbiota composition was observed compared to baseline. The abundance of potentially pathogenic bacteria (Enterobacteriaceae, Enterococcus, and Staphylococcus) was decreased after treatment. The gut microbiota composition was associated with the inflammatory profile and markers of liver fibrosis. Although a significant reduction in the serum levels of cytokines and chemokines was observed post-DAA treatment, measures of intestinal permeability and inflammation remained unchanged.<br><br>CONCLUSIONS: Cure of HCV infection with DAAs in patients with cirrhosis is associated with a modification of the gut microbiota, which correlates with fibrosis and inflammation but does not improve intestinal barrier function.}, }
@article {pmid30345066, year = {2018}, author = {Duran-Pinedo, AE and Solbiati, J and Frias-Lopez, J}, title = {The effect of the stress hormone cortisol on the metatranscriptome of the oral microbiome.}, journal = {NPJ biofilms and microbiomes}, volume = {4}, number = {}, pages = {25}, pmid = {30345066}, issn = {2055-5008}, support = {R01 DE021553/DE/NIDCR NIH HHS/United States ; }, abstract = {Imbalances of the microbiome, also referred to as microbial dysbiosis, could lead to a series of different diseases. One factor that has been shown to lead to dysbiosis of the microbiome is exposure to psychological stressors. Throughout evolution microorganisms of the human microbiome have developed systems for sensing host-associated signals such as hormones associated with those stressors, enabling them to recognize essential changes in their environment, thus changing their expression gene profile to fit the needs of the new environment. The most widely accepted theory explaining the ability of hormones to affect the outcome of an infection involves the suppression of the immune system. Commensal microbiota is involved in stressor-induced immunomodulation, but other biological effects are not yet known. Here we present the impact that cortisol had on the community-wide transcriptome of the oral community. We used a metatranscriptomic approach to obtain first insights into the metabolic changes induced by this stress hormone as well as which members of the oral microbiome respond to the presence of cortisol in the environment. Our findings show that the stress hormone cortisol directly induces shifts in the gene expression profiles of the oral microbiome that reproduce results found in the profiles of expression of periodontal disease and its progression.}, }
@article {pmid30342346, year = {2018}, author = {Chen, B and Wang, J and Wang, Y and Zhang, J and Zhao, C and Shen, N and Yang, J and Gai, Z and Zhang, L}, title = {Oral microbiota dysbiosis and its association with Henoch-Schönlein Purpura in children.}, journal = {International immunopharmacology}, volume = {65}, number = {}, pages = {295-302}, doi = {10.1016/j.intimp.2018.10.017}, pmid = {30342346}, issn = {1878-1705}, mesh = {Adolescent ; Bacteroidetes/*physiology ; Child ; Child, Preschool ; Dysbiosis/immunology/*microbiology ; Female ; Firmicutes/*physiology ; Humans ; IgA Vasculitis/immunology/*microbiology ; Male ; Microbiota/*immunology ; Mouth/*microbiology ; Proteobacteria/*physiology ; RNA, Ribosomal, 16S/genetics ; }, abstract = {BACKGROUND: The pathogenesis of microbes in allergic diseases has been demonstrated and our previous research indicates that microbiota causing gut disorders in children is associated with Henoch-Schönlein Purpura. However, the role of oral microbiota in Henoch-Schönlein Purpura remains unknown.<br><br>METHOD: A total of 164 children were enrolled, of which 98 were patients with HSP and 66 were healthy children. Oral swab samples were collected for DNA extraction and 16S rRNA gene sequencing, then analyzed for oral microbiota composition.<br><br>RESULTS: Oral microbiota differed between healthy children and those with HSP. Children with HSP exhibited higher oral microbial diversity and richness than the controls. Firmicutes, Proteobacteria, and Bacteroidetes are the dominant phyla in children with HSP. We used linear discriminant analysis (LDA) effect size (LEfSe) algorithm and detected 21 bacterial taxonomic clades showing statistical differences (12 increased and 9 decreased) in children with HSP. The correlation analyses between clinical data and abundance in microbial community indicated that an abundance of Butyrivibrio sp. negatively correlated with the length of hospital stay (LOS). Haemophilus sp. negatively correlated to IgE and IgM but positively correlated to LOS, with decreasing significantly in patients with HSP. Prevotella positively correlated with IgM. Prevotella nanceiensis positively correlated with IgA, and were abundant in children with HSP.<br><br>CONCLUSIONS: These results indicate that children with HSP have significantly different oral microbiota compared to healthy children. Although this study does not imply causality, it is helpful to identify the types and pathways of bacteria that can be used to prevent or treat HSP.}, }
@article {pmid30332487, year = {2018}, author = {Wyman, SK and Avila-Herrera, A and Nayfach, S and Pollard, KS}, title = {A most wanted list of conserved microbial protein families with no known domains.}, journal = {PloS one}, volume = {13}, number = {10}, pages = {e0205749}, pmid = {30332487}, issn = {1932-6203}, mesh = {Bacterial Proteins/*chemistry/genetics ; Computational Biology ; *Databases, Nucleic Acid ; Humans ; Metagenome/*genetics ; Metagenomics ; Microbiota/*genetics ; Phylogeny ; Protein Domains/*genetics ; Sequence Homology, Nucleic Acid ; }, abstract = {The number and proportion of genes with no known function are growing rapidly. To quantify this phenomenon and provide criteria for prioritizing genes for functional characterization, we developed a bioinformatics pipeline that identifies robustly defined protein families with no annotated domains, ranks these with respect to phylogenetic breadth, and identifies them in metagenomics data. We applied this approach to 271 965 protein families from the SFams database and discovered many with no functional annotation, including >118 000 families lacking any known protein domain. From these, we prioritized 6 668 conserved protein families with at least three sequences from organisms in at least two distinct classes. These Function Unknown Families (FUnkFams) are present in Tara Oceans Expedition and Human Microbiome Project metagenomes, with distributions associated with sampling environment. Our findings highlight the extent of functional novelty in sequence databases and establish an approach for creating a "most wanted" list of genes to prioritize for further characterization.}, }
@article {pmid30324342, year = {2019}, author = {Waterhouse, M and Hope, B and Krause, L and Morrison, M and Protani, MM and Zakrzewski, M and Neale, RE}, title = {Vitamin D and the gut microbiome: a systematic review of in vivo studies.}, journal = {European journal of nutrition}, volume = {58}, number = {7}, pages = {2895-2910}, pmid = {30324342}, issn = {1436-6215}, mesh = {Animals ; Diet/*methods ; Gastrointestinal Microbiome/*physiology ; Humans ; Mice ; Models, Animal ; Vitamin D/*blood ; Vitamins/*blood ; }, abstract = {PURPOSE: Variation in the human microbiome has been linked with a variety of physiological functions, including immune regulation and metabolism and biosynthesis of vitamins, hormones, and neurotransmitters. Evidence for extraskeletal effects of vitamin D has been accruing and it has been suggested that the effect of vitamin D on health is partially mediated through the microbiome. We aimed to critically evaluate the evidence linking vitamin D and the gastrointestinal microbiome.<br><br>METHODS: We systematically searched the Embase, Web of Science, PubMed and CINAHL databases, including peer-reviewed publications that reported an association between a measure of vitamin D and the gastrointestinal microbiome in humans or experimental animals.<br><br>RESULTS: We included 10 mouse and 14 human studies. Mouse studies compared mice fed diets containing different levels of vitamin D (usually high versus low), or vitamin D receptor knockout or Cyp27B1 knockout with wild-type mice. Five mouse studies reported an increase in Bacteroidetes (or taxa within that phylum) in the low vitamin D diet or gene knockout group. Human studies were predominantly observational; all but two of the included studies found some association between vitamin D and the gut microbiome, but the nature of differences observed varied across studies.<br><br>CONCLUSIONS: Despite substantial heterogeneity, we found evidence to support the hypothesis that vitamin D influences the composition of the gastrointestinal microbiome. However, the research is limited, having been conducted either in mice or in mostly small, selected human populations. Future research in larger population-based studies is needed to fully understand the extent to which vitamin D modulates the microbiome.}, }
@article {pmid30311407, year = {2019}, author = {Bilen, M and Mbogning Fonkou, MD and Khelaifia, S and Tomei, E and Cadoret, F and Daoud, Z and Armstrong, N and Bittar, F and Fournier, PE and Raoult, D and Dubourg, G}, title = {Taxonogenomics description of Parabacteroides timonensis sp. nov. isolated from a human stool sample.}, journal = {MicrobiologyOpen}, volume = {8}, number = {4}, pages = {e00702}, pmid = {30311407}, issn = {2045-8827}, mesh = {Adult ; Bacterial Typing Techniques ; Bacteroidetes/classification/genetics/*isolation &amp; purification ; Base Composition ; DNA, Bacterial/genetics ; Feces/*microbiology ; Gastrointestinal Microbiome ; Genome, Bacterial ; Genomics ; Humans ; Male ; Phylogeny ; RNA, Ribosomal, 16S/genetics ; }, abstract = {Intensive efforts have been made to describe the human microbiome and its involvement in health and disease. Culturomics has been recently adapted to target formerly uncultured bacteria and other unclassified bacterial species. This approach enabled us to isolate in the current study a new bacterial species, Parabacteroides timonensis strain Marseille-P3236[T] , from a stool sample of a healthy 39-year-old pygmy male. This strain, is an anaerobic, gram-negative, nonspore-forming motile rod. Its genome is made up of 6,483,434 bp with 43.41% G+C content, 5046 protein-encoding genes, and 84 RNA genes. We herein provide the full description of Parabacteroides timonensis strain Marseille-P3236[T] through the taxonogenomic approach.}, }
@article {pmid30302512, year = {2019}, author = {Balato, A and Cacciapuoti, S and Di Caprio, R and Marasca, C and Masarà, A and Raimondo, A and Fabbrocini, G}, title = {Human Microbiome: Composition and Role in Inflammatory Skin Diseases.}, journal = {Archivum immunologiae et therapiae experimentalis}, volume = {67}, number = {1}, pages = {1-18}, doi = {10.1007/s00005-018-0528-4}, pmid = {30302512}, issn = {1661-4917}, mesh = {Acne Vulgaris/drug therapy/immunology/*microbiology ; Adolescent ; Adult ; Age Factors ; Aged ; Aged, 80 and over ; Anti-Bacterial Agents/therapeutic use ; Anti-Inflammatory Agents/therapeutic use ; *Bacteria/classification/drug effects/immunology/pathogenicity ; Child ; Child, Preschool ; Dermatitis, Atopic/drug therapy/immunology/*microbiology ; Dermatologic Agents/therapeutic use ; Dysbiosis ; *Gastrointestinal Microbiome/drug effects ; Hidradenitis Suppurativa/drug therapy/immunology/*microbiology ; Host-Pathogen Interactions ; Humans ; Infant ; Infant, Newborn ; Middle Aged ; Psoriasis/drug therapy/immunology/*microbiology ; Skin/drug effects/immunology/*microbiology ; Young Adult ; }, abstract = {This review focuses on recent evidences about human microbiome composition and functions, exploring the potential implication of its impairment in some diffuse and invalidating inflammatory skin diseases, such as atopic dermatitis, psoriasis, hidradenitis suppurativa and acne. We analysed current scientific literature, focusing on the current evidences about gut and skin microbiome composition and the complex dialogue between microbes and the host. Finally, we examined the consequences of this dialogue for health and skin diseases. This review highlights how human microbes interact with different anatomic niches modifying the state of immune activation, skin barrier status, microbe-host and microbe-microbe interactions. It also shows as most of the factors affecting gut and skin microorganisms' activity have demonstrated to be effective also in modulating chronic inflammatory skin diseases. More and more evidences demonstrate that human microbiome plays a key role in human health and diseases. It is to be expected that these new insights will translate into diagnostic, therapeutic and preventive measures in the context of personalized/precision medicine.}, }
@article {pmid30298527, year = {2019}, author = {Bell, JS and Spencer, JI and Yates, RL and Yee, SA and Jacobs, BM and DeLuca, GC}, title = {Invited Review: From nose to gut - the role of the microbiome in neurological disease.}, journal = {Neuropathology and applied neurobiology}, volume = {45}, number = {3}, pages = {195-215}, doi = {10.1111/nan.12520}, pmid = {30298527}, issn = {1365-2990}, mesh = {Alzheimer Disease/complications/*microbiology ; Dysbiosis/*microbiology ; Humans ; Inflammation/*microbiology ; Intestines/*microbiology ; Lung/*microbiology ; *Microbiota ; Mouth/*microbiology ; Multiple Sclerosis/complications/*microbiology ; Nasal Cavity/*microbiology ; Olfaction Disorders/etiology/*microbiology ; Parkinson Disease/complications/*microbiology ; }, abstract = {Inflammation and neurodegeneration are key features of many chronic neurological diseases, yet the causative mechanisms underlying these processes are poorly understood. There has been mounting interest in the role of the human microbiome in modulating the inflammatory milieu of the central nervous system (CNS) in health and disease. To date, most research has focussed on a gut-brain axis, with other mucosal surfaces being relatively neglected. We herein take the novel approach of comprehensively reviewing the roles of the microbiome across several key mucosal interfaces - the nose, mouth, lung and gut - in health and in Parkinson's disease (PD), Alzheimer's disease (AD) and multiple sclerosis (MS). This review systematically appraises the anatomical and microbiological landscape of each mucosal surface in health and disease before considering relevant mechanisms that may influence the initiation and progression of PD, AD and MS. The cumulative effects of dysbiosis from the nose to the gut may contribute significantly to neurological disease through a wide variety of mechanisms, including direct translocation of bacteria and their products, and modulation of systemic or CNS-specific immunity. This remains an understudied and exciting area for future research and may lead to the development of therapeutic targets for chronic neurological disease.}, }
@article {pmid30298256, year = {2018}, author = {Macklaim, JM and Gloor, GB}, title = {From RNA-seq to Biological Inference: Using Compositional Data Analysis in Meta-Transcriptomics.}, journal = {Methods in molecular biology (Clifton, N.J.)}, volume = {1849}, number = {}, pages = {193-213}, doi = {10.1007/978-1-4939-8728-3_13}, pmid = {30298256}, issn = {1940-6029}, mesh = {Bacteria/classification/*genetics/isolation &amp; purification ; Computational Biology/*methods ; Gene Expression Profiling/*methods ; High-Throughput Nucleotide Sequencing/*methods ; Humans ; *Metagenome ; *Microbiota ; *Transcriptome ; }, abstract = {The proper analysis of high-throughput sequencing datasets of mixed microbial communities (meta-transcriptomics) is substantially more complex than for datasets composed of single organisms. Adapting commonly used RNA-seq methods to the analysis of meta-transcriptome datasets can be misleading and not use all the available information in a consistent manner. However, meta-transcriptomic experiments can be investigated in a principled manner using Bayesian probabilistic modeling of the data at a functional level coupled with analysis under a compositional data analysis paradigm. We present a worked example for the differential functional evaluation of mixed-species microbial communities obtained from human clinical samples that were sequenced on an Illumina platform. We demonstrate methods to functionally map reads directly, conduct a compositionally appropriate exploratory data analysis, evaluate differential relative abundance, and finally identify compositionally associated (constant ratio) functions. Using these approaches we have found that meta-transcriptomic functional analyses are highly reproducible and convey significant information regarding the ecosystem.}, }
@article {pmid30283425, year = {2018}, author = {Hoggard, M and Vesty, A and Wong, G and Montgomery, JM and Fourie, C and Douglas, RG and Biswas, K and Taylor, MW}, title = {Characterizing the Human Mycobiota: A Comparison of Small Subunit rRNA, ITS1, ITS2, and Large Subunit rRNA Genomic Targets.}, journal = {Frontiers in microbiology}, volume = {9}, number = {}, pages = {2208}, pmid = {30283425}, issn = {1664-302X}, abstract = {Interest in the human microbiome has increased dramatically in the last decade. However, much of this research has focused on bacteria, while the composition and roles of their fungal counterparts remain less understood. Furthermore, a variety of methodological approaches have been applied, and the comparability between studies is unclear. This study compared four primer pairs targeting the small subunit (SSU) rRNA (18S), ITS1, ITS2, and large subunit (LSU) rRNA (26S) genomic regions for their ability to accurately characterize fungal communities typical of the human mycobiota. All four target regions of 21 individual fungal mock community taxa were capable of being amplified adequately and sequenced. Mixed mock community analyses revealed marked variability in the ability of each primer pair to accurately characterize a complex community. ITS target regions outperformed LSU and SSU. Of the ITS regions, ITS1 failed to generate sequences for Yarrowia lipolytica and all three Malassezia species when in a mixed community. These findings were further supported in studies of human sinonasal and mouse fecal samples. Based on these analyses, previous studies using ITS1, SSU, or LSU markers may omit key taxa that are identified by the ITS2 marker. Of methods commonly used in human mycobiota studies to date, we recommend selection of the ITS2 marker. Further investigation of more recently developed fungal primer options will be essential to ultimately determine the optimal methodological approach by which future human mycobiota studies ought to be standardized.}, }
@article {pmid30280754, year = {2018}, author = {Romano, L and Gualtieri, P and Nicoletti, F and Merra, G}, title = {Neurodegenerative disorders, gut human microbiome and diet: future research for prevention and supportive therapies.}, journal = {European review for medical and pharmacological sciences}, volume = {22}, number = {18}, pages = {5771-5772}, doi = {10.26355/eurrev_201809_15901}, pmid = {30280754}, issn = {2284-0729}, }
@article {pmid30277147, year = {2018}, author = {Vamanu, E}, title = {Complementary Functional Strategy for Modulation of Human Gut Microbiota.}, journal = {Current pharmaceutical design}, volume = {24}, number = {35}, pages = {4144-4149}, doi = {10.2174/1381612824666181001154242}, pmid = {30277147}, issn = {1873-4286}, mesh = {Agaricales/*chemistry ; Gastrointestinal Microbiome/*drug effects/physiology ; Humans ; Polyphenols/chemistry/*pharmacology ; }, abstract = {Two pathologies commonly associated with gut microbiota dysbiosis are type 2 diabetes and cardiovascular diseases. Since diet and medication are two important causes of microbiome fingerprint modifications, new complementary and alternative methods can include wild edible mushrooms, which serve as functional products, given their properties in modulating the microbial pattern at the colon level. A disturbance in microbial balance translates into the occurrence of degenerative dysfunctions that are also associated with other pathologies, such as obesity, colon cancer. The metagenomic study has enabled the identification of some competitive microbiological and biochemical biomarkers which allow the development of innovative strategies in controling microbial disbalance from human gut. Thus, the aim of this review was to present the significant findings related to human microbiome modulation via the prebiotic effects of wild edible mushrooms as a complementary strategy to modern treatment. Certain mushroom species have been approached and their effects on the microbiota fingerprint of two major target groups are highlighted.}, }
@article {pmid30276729, year = {2019}, author = {Perkins, RC}, title = {Making the Case for Functional Proteomics.}, journal = {Methods in molecular biology (Clifton, N.J.)}, volume = {1871}, number = {}, pages = {1-40}, doi = {10.1007/978-1-4939-8814-3_1}, pmid = {30276729}, issn = {1940-6029}, mesh = {Animals ; Biomarkers ; Drug Discovery/methods ; Genome ; Genomics/methods ; Humans ; Molecular Diagnostic Techniques ; Precision Medicine/methods ; *Proteome ; *Proteomics/methods ; Systems Biology/methods ; }, abstract = {"Making the Case for Functional Proteomics" first differentiates the Functional Proteome from the products of genetic protein expression. Qualitatively, the prevalence of posttranslational modifications (PTMs) virtually insures that individual, functional proteins do not equate to their genetic expression counterparts. Quantitatively, considering the frequency of PTMs and a conservative estimate of the number of functional entities arising from protein interactions, the size of the Functional Proteome exceeds that of the human genome by at least two orders of magnitude. The human genome does not, cannot, map the Functional Proteome. Further, the collective genome of the human microbiome dwarfs the human genome. With these facts established, "Making the Case…" proceeds to examine Functional Proteomics (of which both "gene expression" and "epigenetics" are but parts of a larger whole) within the context of Systems Biology, concluding that functionally related networks comprise the dominant motif for biological activity. Creating just such a network focus is essential in not only expanding basic knowledge but also in applying that knowledge in the pragmatic efforts of drug and biomarker development. Outlines for development of drugs and biomarkers, as well as the realization of precision medicine, within a functional proteomics-based, network motif are provided. The chapter proceeds to asses both the knowledge base and the tools to fully embrace Functional Proteomics. Given the decades-long infatuation with the reductionism of genomics, it is not surprising that both the proteomics knowledge base and tools are assessed as poor to fair. However, even a minor shift in research funding and a renewed challenge to methods developers will rapidly improve the current situation. Adoption of the included "Roadmap" will realistically make the twenty-first century the century of a long-awaited revolution in biology.}, }
@article {pmid30275573, year = {2018}, author = {Gonzalez, A and Navas-Molina, JA and Kosciolek, T and McDonald, D and Vázquez-Baeza, Y and Ackermann, G and DeReus, J and Janssen, S and Swafford, AD and Orchanian, SB and Sanders, JG and Shorenstein, J and Holste, H and Petrus, S and Robbins-Pianka, A and Brislawn, CJ and Wang, M and Rideout, JR and Bolyen, E and Dillon, M and Caporaso, JG and Dorrestein, PC and Knight, R}, title = {Qiita: rapid, web-enabled microbiome meta-analysis.}, journal = {Nature methods}, volume = {15}, number = {10}, pages = {796-798}, pmid = {30275573}, issn = {1548-7105}, support = {P01 DK078669/DK/NIDDK NIH HHS/United States ; R01 MD011389/MD/NIMHD NIH HHS/United States ; R01 HG004872/HG/NHGRI NIH HHS/United States ; R01 HL140976/HL/NHLBI NIH HHS/United States ; P30 MH062512/MH/NIMH NIH HHS/United States ; }, mesh = {Computational Biology/*methods ; Humans ; *Internet ; *Metagenomics ; *Microbiota ; *Software ; User-Computer Interface ; }, abstract = {Multi-omic insights into microbiome function and composition typically advance one study at a time. However, in order for relationships across studies to be fully understood, data must be aggregated into meta-analyses. This makes it possible to generate new hypotheses by finding features that are reproducible across biospecimens and data layers. Qiita dramatically accelerates such integration tasks in a web-based microbiome-comparison platform, which we demonstrate with Human Microbiome Project and Integrative Human Microbiome Project (iHMP) data.}, }
@article {pmid30269615, year = {2018}, author = {Aziz, RK and Hegazy, SM and Yasser, R and Rizkallah, MR and ElRakaiby, MT}, title = {Drug pharmacomicrobiomics and toxicomicrobiomics: from scattered reports to systematic studies of drug-microbiome interactions.}, journal = {Expert opinion on drug metabolism &amp; toxicology}, volume = {14}, number = {10}, pages = {1043-1055}, doi = {10.1080/17425255.2018.1530216}, pmid = {30269615}, issn = {1744-7607}, mesh = {Animals ; Drug-Related Side Effects and Adverse Reactions/*epidemiology ; Gastrointestinal Microbiome ; Humans ; *Microbiota ; Pharmaceutical Preparations/administration &amp; dosage/*metabolism ; Pharmacogenetics/methods ; Precision Medicine/methods ; Toxicogenetics/methods ; }, abstract = {Pharmacomicrobiomics and toxicomicrobiomics study how variations within the human microbiome (the combination of human-associated microbial communities and their genomes) affect drug disposition, action, and toxicity. These emerging fields, interconnecting microbiology, bioinformatics, systems pharmacology, and toxicology, complement pharmacogenomics and toxicogenomics, expanding the scope of precision medicine. Areas covered: This article reviews some of the most recently reported pharmacomicrobiomic and toxicomicrobiomic interactions. Examples include the impact of the human gut microbiota on cardiovascular drugs, natural products, and chemotherapeutic agents, including immune checkpoint inhibitors. Although the gut microbiota has been the most extensively studied, some key drug-microbiome interactions involve vaginal, intratumoral, and environmental bacteria, and are briefly discussed here. Additionally, computational resources, moving the field from cataloging to predicting interactions, are introduced. Expert opinion: The rapid pace of discovery triggered by the Human Microbiome Project is moving pharmacomicrobiomic research from scattered observations to systematic studies focusing on screening microbiome variants against different drug classes. Better representation of all human populations will improve such studies by avoiding sampling bias, and the integration of multiomic studies with designed experiments will allow establishing causation. In the near future, pharmacomicrobiomic testing is expected to be a key step in screening novel drugs and designing precision therapeutics.}, }
@article {pmid30269123, year = {2018}, author = {Hattori, M}, title = {[Ecology and function of human microbiomes.].}, journal = {Clinical calcium}, volume = {28}, number = {10}, pages = {1398-1405}, pmid = {30269123}, issn = {0917-5857}, mesh = {Bacteria ; *Gastrointestinal Microbiome ; High-Throughput Nucleotide Sequencing ; Humans ; Metagenomics ; }, abstract = {Hundreds of trillions of bacteria consisting of ~1,000 species reside in various human body sites to form bacterial communities(microbiomes)specific for the sites. In the past decade, the human microbiome research in the world incredibly advanced by development of a culture-independent metagenomic analysis based on next-generation sequencing technologies. Particularly, current studies have revealed that the human gut microbiome is profoundly associated with the host's health and disease.}, }
@article {pmid30263058, year = {2018}, author = {Maleki Vareki, S and Chanyi, RM and Abdur-Rashid, K and Brennan, L and Burton, JP}, title = {Moving on from Metchnikoff: thinking about microbiome therapeutics in cancer.}, journal = {Ecancermedicalscience}, volume = {12}, number = {}, pages = {867}, pmid = {30263058}, issn = {1754-6605}, abstract = {Precision medicine now needs to also consider the microbiome in oncology treatment. Ingested substances, whether they are a carcinogenic or therapeutic agent, will likely come into contact with the microbiota. Even those delivered extra-intestinally can be influenced beyond xenobiotic metabolism by biochemical factors associated with the microbiota or by an immunological predisposition created by the microbiome. We need to undertake one of the largest paradigm shifts to ever occur in medicine, that is, every drug or ingested substance needs to be re-evaluated for its pharmacological effect post-microbiome interaction. The importance of the microbiome with a focus on the treatment of cancer is discussed. In the near future, it may be possible to specifically manipulate the microbial composition within cancer patients to improve the therapeutic potential of existing oncological agents. However, the current tools to do so are limited. Targeted modulation is likely to be achieved by addition, selective enhancement or depletion of specific microbial types. This may include compounds such as narrow spectrum antimicrobial agents or oligosaccharides that will kill or enhance the bacterial growth of distinct members of the microbiota, respectively. This will stimulate a new era in these fields.}, }
@article {pmid30257907, year = {2019}, author = {Munson, E and Carroll, KC}, title = {An Update on the Novel Genera and Species and Revised Taxonomic Status of Bacterial Organisms Described in 2016 and 2017.}, journal = {Journal of clinical microbiology}, volume = {57}, number = {2}, pages = {}, pmid = {30257907}, issn = {1098-660X}, mesh = {Bacteria/*classification/*isolation &amp; purification ; Bacterial Infections/*microbiology ; Bacteriological Techniques/methods ; Classification/*methods ; Diagnostic Tests, Routine/methods ; Humans ; *Terminology as Topic ; }, abstract = {Recognition and acknowledgment of novel bacterial taxonomy and nomenclature revisions can impact clinical practice, disease epidemiology, and routine clinical microbiology laboratory operations. The Journal of Clinical Microbiology (JCM) herein presents its biannual report summarizing such changes published in the years 2016 and 2017, as published and added by the International Journal of Systematic and Evolutionary Microbiology Noteworthy discussion centers around descriptions of novel Corynebacteriaceae and an anaerobic mycolic acid-producing bacterium in the suborder Corynebacterineae; revisions within the Propionibacterium, Clostridium, Borrelia, and Enterobacter genera; and a major reorganization of the family Enterobacteriaceae. JCM intends to sustain this series of reports as advancements in molecular genetics, whole-genome sequencing, and studies of the human microbiome continue to produce novel taxa and clearer understandings of bacterial relatedness.}, }
@article {pmid30254254, year = {2019}, author = {Nazaroff, WW}, title = {Embracing microbes in exposure science.}, journal = {Journal of exposure science &amp; environmental epidemiology}, volume = {29}, number = {1}, pages = {1-10}, pmid = {30254254}, issn = {1559-064X}, mesh = {Communicable Diseases/microbiology ; Environmental Exposure/*statistics &amp; numerical data ; Environmental Health/*trends ; Environmental Medicine/*trends ; Humans ; Infectious Disease Medicine/*trends ; Public Health ; }, abstract = {Although defined more broadly, exposure science has mainly focused on exposures to environmental chemicals and related stressors, such as airborne particulate matter. There is an opportunity for exposure science to contribute more substantially to improving public health by devoting more attention to microorganisms as key stressors and agents in exposure. The discovery that pathogenic microbes cause disease in humans precipitated a revolution in public health science and disease prevention. With a continued global urgency to address spread of pathogenic microbes, contributions of microorganisms to both infectious and noninfectious processes merit more attention from the exposure science community. Today, discoveries of the importance of the human microbiome as a determinant of health and disease are precipitating a second revolution. Emerging knowledge creates a major opportunity to expand the scope of exposure science to incorporate the human microbiome as a target and modulator of exposure. A study committee of the National Academies of Sciences, Engineering, and Medicine has defined a research strategy to address health risks that pertain to the interaction of environmental chemicals with the human microbiome. Some aspects of this strategy pose important challenges and opportunities for the exposure science community.}, }
@article {pmid30250232, year = {2018}, author = {Zhao, Y and Chen, B and Li, S and Yang, L and Zhu, D and Wang, Y and Wang, H and Wang, T and Shi, B and Gai, Z and Yang, J and Heng, X and Yang, J and Zhang, L}, title = {Detection and characterization of bacterial nucleic acids in culture-negative synovial tissue and fluid samples from rheumatoid arthritis or osteoarthritis patients.}, journal = {Scientific reports}, volume = {8}, number = {1}, pages = {14305}, pmid = {30250232}, issn = {2045-2322}, support = {31471202//Foundation for the National Institutes of Health (Foundation for the National Institutes of Health, Inc.)/International ; ZR2014YL040//Natural Science Foundation of Shandong Province (Shandong Provincial Natural Science Foundation)/International ; }, mesh = {Adult ; Algorithms ; Arthritis, Rheumatoid/*microbiology ; Bacteria/*genetics ; Cytokines/metabolism ; Discriminant Analysis ; Humans ; Microbiota ; Nucleic Acids/*analysis ; Osteoarthritis/*microbiology ; Principal Component Analysis ; Synovial Fluid/*microbiology ; Synovial Membrane/*microbiology ; }, abstract = {Human intestinal microbes can mediate development of arthritis - Studies indicate that certain bacterial nucleic acids may exist in synovial fluid (SF) and could be involved in arthritis, although the underlying mechanism remains unclear. To characterize potential SF bacterial nucleic acids, we used 16S rRNA gene amplicon sequencing to assess bacterial nucleic acid communities in 15 synovial tissue (ST) and 110 SF samples from 125 patients with rheumatoid arthritis (RA) and 16 ST and 42 SF samples from 58 patients with osteoarthritis (OA). Our results showed an abundant diversity of bacterial nucleic acids in these clinical samples, including presence of Porphyromonas and Bacteroides in all 183 samples. Agrobacterium, Comamonas, Kocuria, Meiothermus, and Rhodoplanes were more abundant in synovial tissues of rheumatoid arthritis (STRA). Atopobium, Phascolarctobacterium, Rhodotorula mucilaginosa, Bacteroides uniformis, Rothia, Megasphaera, Turicibacter, Leptotrichia, Haemophilus parainfluenzae, Bacteroides fragilis, Porphyromonas, and Streptococcus were more abundant in synovial tissues of osteoarthritis (STOA). Veillonella dispar, Haemophilus parainfluenzae, Prevotella copri and Treponema amylovorum were more abundant in synovial fluid of rheumatoid arthritis (SFRA), while Bacteroides caccae was more abundant in the synovial fluid of osteoarthritis (SFOA). Overall, this study confirms existence of bacterial nucleic acids in SF and ST samples of RA and OA lesions and reveals potential correlations with degree of disease.}, }
@article {pmid30243649, year = {2018}, author = {Wang, N and Zhu, F and Chen, L and Chen, K}, title = {Proteomics, metabolomics and metagenomics for type 2 diabetes and its complications.}, journal = {Life sciences}, volume = {212}, number = {}, pages = {194-202}, doi = {10.1016/j.lfs.2018.09.035}, pmid = {30243649}, issn = {1879-0631}, mesh = {Animals ; Biomarkers/*analysis ; Diabetes Complications/*diagnosis/genetics/metabolism ; Diabetes Mellitus, Type 2/*diagnosis/genetics/metabolism ; Humans ; Metabolomics/*methods ; Metagenomics/*methods ; Proteomics/*methods ; }, abstract = {Type 2 diabetes mellitus (T2DM) is one of the most common diseases of endocrine and metabolic disorders, whose mechanism is still largely unknown. Fortunately, various "omics" tools have been employed to better understand the progression pathologies of T2DM and its complications. More specifically, proteomics, metabolomics and metagenomics have played crucial roles in advancing deeper understanding of the physiological processes and regulatory mechanisms of T2DM, such as regulation of signaling pathways perturbed by glucose levels, intestinal microorganism, and inflammation and so on. By analyzing the dynamic change and modification of proteins, proteomics has become an important tool in biology and medicine. Metabolomic analysis can amplify and quantify metabolites in living organisms to reveal the relative relationship between metabolites and physiological and pathological changes. There are also increasing evidences that the human microbiome, specifically the gastrointestinal microbiome have a potential role in the etiology and pathological outcomes of T2DM and its complications. This article summarized and discussed the recent applications of these "omics" tools in finding biomarkers for T2DM and its complications. We also reviewed employing multiple "omics" to further advance our understanding of this pathology. This review will benefit deeper understanding in new therapeutic and/or diagnostic biological target for the discovery of T2DM and its complications.}, }
@article {pmid30240894, year = {2019}, author = {Allaband, C and McDonald, D and Vázquez-Baeza, Y and Minich, JJ and Tripathi, A and Brenner, DA and Loomba, R and Smarr, L and Sandborn, WJ and Schnabl, B and Dorrestein, P and Zarrinpar, A and Knight, R}, title = {Microbiome 101: Studying, Analyzing, and Interpreting Gut Microbiome Data for Clinicians.}, journal = {Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association}, volume = {17}, number = {2}, pages = {218-230}, pmid = {30240894}, issn = {1542-7714}, support = {K08 DK102902/DK/NIDDK NIH HHS/United States ; }, mesh = {Computational Biology/*methods ; *Gastrointestinal Microbiome ; Gastrointestinal Tract/*microbiology ; Humans ; Individuality ; Metabolomics/*methods ; Metagenomics/*methods ; *Microbiota ; }, abstract = {Advances in technical capabilities for reading complex human microbiomes are leading to an explosion of microbiome research, leading in turn to intense interest among clinicians in applying these techniques to their patients. In this review, we discuss the content of the human microbiome, including intersubject and intrasubject variability, considerations of study design including important confounding factors, and different methods in the laboratory and on the computer to read the microbiome and its resulting gene products and metabolites. We highlight several common pitfalls for clinicians, including the expectation that an individual's microbiome will be stable, that diet can induce rapid changes that are large compared with the differences among subjects, that everyone has essentially the same core stool microbiome, and that different laboratory and computational methods will yield essentially the same results. We also highlight the current limitations and future promise of these techniques, with the expectation that an understanding of these considerations will help accelerate the path toward routine clinical application of these techniques developed in research settings.}, }
@article {pmid30240703, year = {2019}, author = {Kyburz, A and Fallegger, A and Zhang, X and Altobelli, A and Artola-Boran, M and Borbet, T and Urban, S and Paul, P and Münz, C and Floess, S and Huehn, J and Cover, TL and Blaser, MJ and Taube, C and Müller, A}, title = {Transmaternal Helicobacter pylori exposure reduces allergic airway inflammation in offspring through regulatory T cells.}, journal = {The Journal of allergy and clinical immunology}, volume = {143}, number = {4}, pages = {1496-1512.e11}, pmid = {30240703}, issn = {1097-6825}, support = {TL1 TR001447/TR/NCATS NIH HHS/United States ; UL1 TR001445/TR/NCATS NIH HHS/United States ; P30 CA016087/CA/NCI NIH HHS/United States ; P30 DK058404/DK/NIDDK NIH HHS/United States ; P01 CA116087/CA/NCI NIH HHS/United States ; I01 BX000627/BX/BLRD VA/United States ; R01 AI039657/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Female ; Helicobacter Infections/*immunology ; Immune Tolerance/immunology ; Mice, Inbred C57BL ; Pregnancy ; Prenatal Exposure Delayed Effects/*immunology/*microbiology ; Respiratory Hypersensitivity/*immunology/*microbiology ; T-Lymphocytes, Regulatory/*immunology ; }, abstract = {BACKGROUND: Transmaternal exposure to tobacco, microbes, nutrients, and other environmental factors shapes the fetal immune system through epigenetic processes. The gastric microbe Helicobacter pylori represents an ancestral constituent of the human microbiota that causes gastric disorders on the one hand and is inversely associated with allergies and chronic inflammatory conditions on the other.<br><br>OBJECTIVE: Here we investigate the consequences of transmaternal exposure to H pylori in utero and/or during lactation for susceptibility to viral and bacterial infection, predisposition to allergic airway inflammation, and development of immune cell populations in the lungs and lymphoid organs.<br><br>METHODS: We use experimental models of house dust mite- or ovalbumin-induced airway inflammation and influenza A&#xa0;virus or Citrobacter rodentium infection along with metagenomics analyses, multicolor flow cytometry, and bisulfite pyrosequencing, to study the effects of H pylori on allergy severity and immunologic and microbiome correlates thereof.<br><br>RESULTS: Perinatal exposure to H pylori extract or its immunomodulator vacuolating cytotoxin confers robust protective effects against allergic airway inflammation not only in first- but also second-generation offspring but does not increase susceptibility to viral or bacterial infection. Immune correlates of allergy protection include skewing of regulatory over effector T cells, expansion of regulatory T-cell subsets expressing CXCR3 or retinoic acid-related orphan receptor &#x3b3;t, and demethylation of the forkhead box P3 (FOXP3) locus. The composition and diversity of the gastrointestinal microbiota is measurably affected by perinatal H pylori exposure.<br><br>CONCLUSION: We conclude that exposure to H pylori has consequences not only for the carrier but also for subsequent generations that can be exploited for interventional purposes.}, }
@article {pmid30230652, year = {2018}, author = {Little, MS and Ervin, SM and Walton, WG and Tripathy, A and Xu, Y and Liu, J and Redinbo, MR}, title = {Active site flexibility revealed in crystal structures of Parabacteroides merdae β-glucuronidase from the human gut microbiome.}, journal = {Protein science : a publication of the Protein Society}, volume = {27}, number = {12}, pages = {2010-2022}, pmid = {30230652}, issn = {1469-896X}, support = {P30 ES010126/ES/NIEHS NIH HHS/United States ; R01 CA207416/CA/NCI NIH HHS/United States ; }, mesh = {Bacteroidaceae/*enzymology ; Catalytic Domain ; Crystallography, X-Ray ; *Gastrointestinal Microbiome ; Glucuronidase/*metabolism ; Humans ; Models, Molecular ; Protein Conformation ; }, abstract = {β-Glucuronidase (GUS) enzymes in the gastrointestinal tract are involved in maintaining mammalian-microbial symbiosis and can play key roles in drug efficacy and toxicity. Parabacteroides merdae GUS was identified as an abundant mini-Loop 2 (mL2) type GUS enzyme in the Human Microbiome Project gut metagenomic database. Here, we report the crystal structure of P. merdae GUS and highlight the differences between this enzyme and extant structures of gut microbial GUS proteins. We find that P. merdae GUS exhibits a distinct tetrameric quaternary structure and that the mL2 motif traces a unique path within the active site, which also includes two arginines distinctive to this GUS. We observe two states of the P. merdae GUS active site; a loop repositions itself by more than 50 Å to place a functionally-relevant residue into the enzyme's catalytic site. Finally, we find that P. merdae GUS is able to bind to homo and heteropolymers of the polysaccharide alginic acid. Together, these data broaden our understanding of the structural and functional diversity in the GUS family of enzymes present in the human gut microbiome and point to specialization as an important feature of microbial GUS orthologs.}, }
@article {pmid30224943, year = {2018}, author = {Randolph, TW and Zhao, S and Copeland, W and Hullar, M and Shojaie, A}, title = {KERNEL-PENALIZED REGRESSION FOR ANALYSIS OF MICROBIOME DATA.}, journal = {The annals of applied statistics}, volume = {12}, number = {1}, pages = {540-566}, pmid = {30224943}, issn = {1932-6157}, support = {K01 HL124050/HL/NHLBI NIH HHS/United States ; P01 CA168530/CA/NCI NIH HHS/United States ; R01 GM114029/GM/NIGMS NIH HHS/United States ; U01 CA162077/CA/NCI NIH HHS/United States ; }, abstract = {The analysis of human microbiome data is often based on dimension-reduced graphical displays and clusterings derived from vectors of microbial abundances in each sample. Common to these ordination methods is the use of biologically motivated definitions of similarity. Principal coordinate analysis, in particular, is often performed using ecologically defined distances, allowing analyses to incorporate context-dependent, non-Euclidean structure. In this paper, we go beyond dimension-reduced ordination methods and describe a framework of high-dimensional regression models that extends these distance-based methods. In particular, we use kernel-based methods to show how to incorporate a variety of extrinsic information, such as phylogeny, into penalized regression models that estimate taxonspecific associations with a phenotype or clinical outcome. Further, we show how this regression framework can be used to address the compositional nature of multivariate predictors comprised of relative abundances; that is, vectors whose entries sum to a constant. We illustrate this approach with several simulations using data from two recent studies on gut and vaginal microbiomes. We conclude with an application to our own data, where we also incorporate a significance test for the estimated coefficients that represent associations between microbial abundance and a percent fat.}, }
@article {pmid30223687, year = {2019}, author = {Lin, H and He, QY and Shi, L and Sleeman, M and Baker, MS and Nice, EC}, title = {Proteomics and the microbiome: pitfalls and potential.}, journal = {Expert review of proteomics}, volume = {16}, number = {6}, pages = {501-511}, doi = {10.1080/14789450.2018.1523724}, pmid = {30223687}, issn = {1744-8387}, mesh = {Animals ; Biomarkers/metabolism ; Feces/microbiology ; Gastrointestinal Microbiome/physiology ; Humans ; Microbiota/*physiology ; Precision Medicine ; Proteomics/*methods ; }, abstract = {Introduction: Human symbiotic microbiota are now known to play important roles in human health and disease. Significant progress in our understanding of the human microbiome has been driven by recent technological advances in the fields of genomics, transcriptomics, and proteomics. As a complementary method to metagenomics, proteomics is enabling detailed protein profiling of the microbiome to decipher its structure and function and to analyze its relationship with the human body. Fecal proteomics is being increasingly applied to discover and validate potential health and disease biomarkers, and Therapeutic Goods Administration (TGA)-approved instrumentation and a range of clinical assays are being developed that will collectively play key roles in advancing personalized medicine. Areas covered: This review will introduce the complexity of the microbiome and its role in health and disease (in particular the gastrointestinal tract or gut microbiome), discuss current genomic and proteomic methods for studying this system, including the discovery of potential biomarkers, and outline the development of clinically accepted protocols leading to personalized medicine. Expert commentary: Recognition of the important role the microbiome plays in both health and disease is driving current research in this key area. A proteogenomics approach will be essential to unravel the biologies underlying this complex network.}, }
@article {pmid30218543, year = {2018}, author = {Zhan, X and Xue, L and Zheng, H and Plantinga, A and Wu, MC and Schaid, DJ and Zhao, N and Chen, J}, title = {A small-sample kernel association test for correlated data with application to microbiome association studies.}, journal = {Genetic epidemiology}, volume = {42}, number = {8}, pages = {772-782}, doi = {10.1002/gepi.22160}, pmid = {30218543}, issn = {1098-2272}, support = {GM065450/NH/NIH HHS/United States ; }, mesh = {*Algorithms ; Computer Simulation ; Humans ; Linear Models ; *Microbiota/genetics ; Models, Genetic ; Sample Size ; Twins ; United Kingdom ; }, abstract = {Recent research has highlighted the importance of the human microbiome in many human disease and health conditions. Most current microbiome association analyses focus on unrelated samples; such methods are not appropriate for analysis of data collected from more advanced study designs such as longitudinal and pedigree studies, where outcomes can be correlated. Ignoring such correlations can sometimes lead to suboptimal results or even possibly biased conclusions. Thus, new methods to handle correlated outcome data in microbiome association studies are needed. In this paper, we propose the correlated sequence kernel association test (CSKAT) to address such correlations using the linear mixed model. Specifically, random effects are used to account for the outcome correlations and a variance component test is used to examine the microbiome effect. Compared to existing genetic association tests for longitudinal and family samples, we implement a correction procedure to better calibrate the null distribution of the score test statistic to accommodate the small sample size nature of data collected from a typical microbiome study. Comprehensive simulation studies are conducted to demonstrate the validity and efficiency of our method, and we show that CSKAT achieves a higher power than existing methods while correctly controlling the Type I error rate. We also apply our method to a microbiome data set collected from a UK twin study to illustrate its potential usefulness. A free implementation of our method in R software is available at https://github.com/jchen1981/SSKAT.}, }
@article {pmid30214898, year = {2018}, author = {Trinh, P and Zaneveld, JR and Safranek, S and Rabinowitz, PM}, title = {One Health Relationships Between Human, Animal, and Environmental Microbiomes: A Mini-Review.}, journal = {Frontiers in public health}, volume = {6}, number = {}, pages = {235}, pmid = {30214898}, issn = {2296-2565}, support = {T32 ES015459/ES/NIEHS NIH HHS/United States ; }, abstract = {The One Health concept stresses the ecological relationships between human, animal, and environmental health. Much of the One Health literature to date has examined the transfer of pathogens from animals (e.g., emerging zoonoses) and the environment to humans. The recent rapid development of technology to perform high throughput DNA sequencing has expanded this view to include the study of entire microbial communities. Applying the One Health approach to the microbiome allows for consideration of both pathogenic and non-pathogenic microbial transfer between humans, animals, and the environment. We review recent research studies of such transmission, the molecular and statistical methods being used, and the implications of such microbiome relationships for human health. Our review identified evidence that the environmental microbiome as well as the microbiome of animals in close contact can affect both the human microbiome and human health outcomes. Such microbiome transfer can take place in the household as well as the workplace setting. Urbanization of built environments leads to changes in the environmental microbiome which could be a factor in human health. While affected by environmental exposures, the human microbiome also can modulate the response to environmental factors through effects on metabolic and immune function. Better understanding of these microbiome interactions between humans, animals, and the shared environment will require continued development of improved statistical and ecological modeling approaches. Such enhanced understanding could lead to innovative interventions to prevent and manage a variety of human health and disease states.}, }
@article {pmid30212271, year = {2019}, author = {Ossorio, PN and Zhou, Y}, title = {Regulating stool for microbiota transplantation.}, journal = {Gut microbes}, volume = {10}, number = {2}, pages = {105-108}, pmid = {30212271}, issn = {1949-0984}, mesh = {Fecal Microbiota Transplantation ; Feces ; *Gastrointestinal Microbiome ; Humans ; *Microbiota ; }, abstract = {In 2017 Gut Microbes published "A proposed definition of microbiota transplantation for regulatory purposes," in which the authors suggest that regulators should draw a line between microbiota transplants and biologic drugs composed of microbial communities (or other products derived from the human microbiome). They develop a definition of microbiota transplantation (MT) to help regulators draw such a line, and suggest that MT need not be, and cannot be, regulated as a biologic drug (a live biotherapeutic product). However, an agency's regulatory scrutiny of a medical product should be commensurate with that product's degree of risk to patients. Products for MT, such as stool, are likely to be as or more dangerous than more highly manipulated microbial products that scientists and regulators agree should be regulated as biologic drugs. Therefore, we argue that MT, as defined by the authors, should receive the same regulatory oversight as any other biologic product intended to cure, mitigate, treat, or prevent disease. We also suggest that regulators might not be able to operationalize the proposed definition of MT.}, }
@article {pmid30211213, year = {2018}, author = {Alves, LF and Westmann, CA and Lovate, GL and de Siqueira, GMV and Borelli, TC and Guazzaroni, ME}, title = {Metagenomic Approaches for Understanding New Concepts in Microbial Science.}, journal = {International journal of genomics}, volume = {2018}, number = {}, pages = {2312987}, pmid = {30211213}, issn = {2314-436X}, abstract = {Over the past thirty years, since the dawn of metagenomic studies, a completely new (micro) universe was revealed, with the potential to have profound impacts on many aspects of the society. Remarkably, the study of human microbiome provided a new perspective on a myriad of human traits previously regarded as solely (epi-) genetically encoded, such as disease susceptibility, immunological response, and social and nutritional behaviors. In this context, metagenomics has established a powerful framework for understanding the intricate connections between human societies and microbial communities, ultimately allowing for the optimization of both human health and productivity. Thus, we have shifted from the old concept of microbes as harmful organisms to a broader panorama, in which the signal of the relationship between humans and microbes is flexible and directly dependent on our own decisions and practices. In parallel, metagenomics has also been playing a major role in the prospection of "hidden" genetic features and the development of biotechnological applications, through the discovery of novel genes, enzymes, pathways, and bioactive molecules with completely new or improved biochemical functions. Therefore, this review highlights the major milestones over the last three decades of metagenomics, providing insights into both its potentialities and current challenges.}, }
@article {pmid30205462, year = {2018}, author = {Hidalgo-Cantabrana, C and Sanozky-Dawes, R and Barrangou, R}, title = {Insights into the Human Virome Using CRISPR Spacers from Microbiomes.}, journal = {Viruses}, volume = {10}, number = {9}, pages = {}, pmid = {30205462}, issn = {1999-4915}, support = {support//North Carolina Agricultural Foundation/International ; internal support//North Carolina State University/International ; }, mesh = {*Biodiversity ; Clustered Regularly Interspaced Short Palindromic Repeats ; Humans ; Metagenomics ; *Microbiota ; Viruses/*classification/genetics/*isolation &amp; purification ; }, abstract = {Due to recent advances in next-generation sequencing over the past decade, our understanding of the human microbiome and its relationship to health and disease has increased dramatically. Yet, our insights into the human virome, and its interplay with important microbes that impact human health, is relatively limited. Prokaryotic and eukaryotic viruses are present throughout the human body, comprising a large and diverse population which influences several niches and impacts our health at various body sites. The presence of prokaryotic viruses like phages, has been documented at many different body sites, with the human gut being the richest ecological niche. Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) and associated proteins constitute the adaptive immune system of bacteria, which prevents attack by invasive nucleic acid. CRISPR-Cas systems function by uptake and integration of foreign genetic element sequences into the CRISPR array, which constitutes a genomic archive of iterative vaccination events. Consequently, CRISPR spacers can be investigated to reconstruct interplay between viruses and bacteria, and metagenomic sequencing data can be exploited to provide insights into host-phage interactions within a niche. Here, we show how the CRISPR spacer content of commensal and pathogenic bacteria can be used to determine the evidence of their phage exposure. This framework opens new opportunities for investigating host-virus dynamics in metagenomic data, and highlights the need to dedicate more efforts for virome sampling and sequencing.}, }
@article {pmid30205429, year = {2018}, author = {Hendler, R and Zhang, Y}, title = {Probiotics in the Treatment of Colorectal Cancer.}, journal = {Medicines (Basel, Switzerland)}, volume = {5}, number = {3}, pages = {}, pmid = {30205429}, issn = {2305-6320}, abstract = {The human microbiome plays many roles in inflammation, drug metabolism, and even the development of cancer that we are only beginning to understand. Colorectal cancer has been a focus for study in this field as its pathogenesis and its response to treatment have both been linked to the functioning of microbiota. This literature review evaluates the animal and human studies that have explored this relationship. By manipulating the microbiome with interventions such as probiotic administration, we may be able to reduce colorectal cancer risk and improve the safety and effectiveness of cancer therapy even though additional clinical research is still necessary.}, }
@article {pmid30197908, year = {2017}, author = {Xia, Y and Sun, J}, title = {Hypothesis Testing and Statistical Analysis of Microbiome.}, journal = {Genes &amp; diseases}, volume = {4}, number = {3}, pages = {138-148}, pmid = {30197908}, issn = {2352-4820}, support = {R01 DK105118/DK/NIDDK NIH HHS/United States ; R01 DK114126/DK/NIDDK NIH HHS/United States ; }, abstract = {After the initiation of Human Microbiome Project in 2008, various biostatistic and bioinformatic tools for data analysis and computational methods have been developed and applied to microbiome studies. In this review and perspective, we discuss the research and statistical hypotheses in gut microbiome studies, focusing on mechanistic concepts that underlie the complex relationships among host, microbiome, and environment. We review the current available statistic tools and highlight recent progress of newly developed statistical methods and models. Given the current challenges and limitations in biostatistic approaches and tools, we discuss the future direction in developing statistical methods and models for the microbiome studies.}, }
@article {pmid30196160, year = {2019}, author = {Dong, TS and Gupta, A}, title = {Influence of Early Life, Diet, and the Environment on the Microbiome.}, journal = {Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association}, volume = {17}, number = {2}, pages = {231-242}, pmid = {30196160}, issn = {1542-7714}, support = {K23 DK106528/DK/NIDDK NIH HHS/United States ; R03 DK121025/DK/NIDDK NIH HHS/United States ; T32 DK007180/DK/NIDDK NIH HHS/United States ; }, mesh = {Diet/*methods ; *Environmental Exposure ; *Gastrointestinal Microbiome ; *Host Microbial Interactions ; Humans ; Infant ; Infant, Newborn ; *Microbiota ; }, abstract = {Advances in sequencing technology and bioinformatics have greatly enhanced our ability to understand the human microbiome. Over the last decade, a growing body of literature has linked nutrition and the environment to the microbiome and is now thought to be an important contributor to overall health. This paper reviews the literature from the past 10 years to highlight the influence of environmental factors such as diet, early life adversity and stress in shaping and modifying our microbiome towards health and disease. The review shows that many factors such as the mode of delivery, breast milk, stress, diet and medications can greatly influence the development of our gut microbiome and potentially make us more prone to certain diseases. By incorporating environmental factors into models that study the microbiome in the setting of health and disease, may provide a better understanding of disease and potentially new areas of treatment. To highlight this, we will additionally explore the role of the environment and the microbiome in the development of obesity and functional bowel disorders.}, }
@article {pmid30195150, year = {2018}, author = {Sharma, A and Gilbert, JA}, title = {Microbial exposure and human health.}, journal = {Current opinion in microbiology}, volume = {44}, number = {}, pages = {79-87}, doi = {10.1016/j.mib.2018.08.003}, pmid = {30195150}, issn = {1879-0364}, mesh = {Bacteria/classification/genetics/growth &amp; development/isolation &amp; purification ; Fungi/classification/genetics/growth &amp; development/isolation &amp; purification ; *Gastrointestinal Microbiome ; *Health ; Humans ; Immunity ; *Microbiota ; }, abstract = {The human body comprises of micro-ecosystem made up of trillions of microbes (i.e. bacteria, archaea, fungi, protists and viruses). The total microbial gene content, which is referred to as the human microbiome, is fundamental to human physiology and immunity. There exists an intricate relationship between the surrounding microbial world (i.e. the environment) and the endogenous human microbiome, mediated by the immune system. Disrupting this relationship can a profound effect on human health and disease. Understanding how microbial exposure influences immune response and the feedback on endogenous microbial metabolic activity could have profound implications for the development of novel microbial therapeutics. The term 'microbial exposure' is used generally to refer to exogenous environmental microbial interaction, while 'exposome' accounts for both the environmental exposures and the impact of lifestyle-associated microbial impacts, such as diet influences on endogenous microbial metabolism. In this review, we focus on how environment and lifestyle-associated microbial exposures shape the human immune system and microbiome, and how the resulting changes can shape human health, especially during critical developmental windows, that is prenatal, postnatal and adult. We conclude this review by proposing approaches to characterize the microbial exposome so as to accelerate the development of a precision microbial therapeutics for both practical and clinical intervention.}, }
@article {pmid30189627, year = {2018}, author = {Di Francesco, L and Di Girolamo, F and Mennini, M and Masotti, A and Salvatori, G and Rigon, G and Signore, F and Pietrantoni, E and Scapaticci, M and Lante, I and Goffredo, BM and Mazzina, O and Elbousify, AI and Roncada, P and Dotta, A and Fiocchi, A and Putignani, L}, title = {A MALDI-TOF MS Approach for Mammalian, Human, and Formula Milks' Profiling.}, journal = {Nutrients}, volume = {10}, number = {9}, pages = {}, pmid = {30189627}, issn = {2072-6643}, support = {I Fellowship Program//San Camillo Hospital, Treviso, Italy/ ; }, mesh = {Animals ; Camelus ; Equidae ; Food Contamination ; Humans ; Infant ; Infant Formula/*chemistry ; Infant, Newborn ; *Mammals ; Milk/*chemistry ; Milk Proteins/*analysis ; Milk, Human/chemistry ; Multivariate Analysis ; Peptides/*analysis ; Proteomics/*methods ; Ruminants ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization/*methods ; }, abstract = {Human milk composition is dynamic, and substitute formulae are intended to mimic its protein content. The purpose of this study was to investigate the potentiality of matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry (MALDI-TOF MS), followed by multivariate data analyses as a tool to analyze the peptide profiles of mammalian, human, and formula milks. Breast milk samples from women at different lactation stages (2 (n = 5), 30 (n = 6), 60 (n = 5), and 90 (n = 4) days postpartum), and milk from donkeys (n = 4), cows (n = 4), buffaloes (n = 7), goats (n = 4), ewes (n = 5), and camels (n = 2) were collected. Different brands (n = 4) of infant formulae were also analyzed. Protein content (<30 kDa) was analyzed by MS, and data were exported for statistical elaborations. The mass spectra for each milk closely clustered together, whereas different milk samples resulted in well-separated mass spectra. Human samples formed a cluster in which colostrum constituted a well-defined subcluster. None of the milk formulae correlated with animal or human milk, although they were specifically characterized and correlated well with each other. These findings propose MALDI-TOF MS milk profiling as an analytical tool to discriminate, in a blinded way, different milk types. As each formula has a distinct specificity, shifting a baby from one to another formula implies a specific proteomic exposure. These profiles may assist in milk proteomics for easiness of use and minimization of costs, suggesting that the MALDI-TOF MS pipelines may be useful for not only milk adulteration assessments but also for the characterization of banked milk specimens in pediatric clinical settings.}, }
@article {pmid30183502, year = {2019}, author = {Strouse, C and Mangalam, A and Zhang, J}, title = {Bugs in the system: bringing the human microbiome to bear in cancer immunotherapy.}, journal = {Gut microbes}, volume = {10}, number = {2}, pages = {109-112}, pmid = {30183502}, issn = {1949-0984}, support = {P30 CA086862/CA/NCI NIH HHS/United States ; P30 ES005605/ES/NIEHS NIH HHS/United States ; }, mesh = {Anti-Bacterial Agents/pharmacology/therapeutic use ; Antibodies, Monoclonal/therapeutic use ; Dysbiosis/immunology/microbiology/therapy ; Fecal Microbiota Transplantation ; Humans ; *Immunotherapy ; Microbiota/drug effects/genetics/*immunology ; Neoplasms/immunology/*microbiology/*therapy ; }, abstract = {The influence of the composition of the human microbiome on the efficacy of cancer directed immunotherapies, such as antibodies directed against the programmed cell death 1 protein (PD-1) or its ligand (PD-L1), has garnered increasing attention as the role of immunotherapies in the care of cancer has grown. Dysbiosis (altered microbiota) has recently been reported to adversely affect the efficacy of cancer directed immunotherapies, and correction of this dysbiosis has the potential to improve the efficacy of these treatments. However, the exact mechanisms underlying this relationship remains unknown. Current methods for characterizing the microbiome likely capture only a small portion of the highly complex interaction between the microbiome and the immune system. Here we discuss the recent reports of the influence of dysbiosis on cancer immunotherapy, methods to more fully characterize the interaction between the microbiome and the immune system, and methods of modulating the immune system to improve the efficacy of cancer immunotherapy.}, }
@article {pmid30181300, year = {2018}, author = {Neil, JA and Cadwell, K}, title = {The Intestinal Virome and Immunity.}, journal = {Journal of immunology (Baltimore, Md. : 1950)}, volume = {201}, number = {6}, pages = {1615-1624}, pmid = {30181300}, issn = {1550-6606}, support = {R01 AI121244/AI/NIAID NIH HHS/United States ; R01 DK093668/DK/NIDDK NIH HHS/United States ; R01 DK103788/DK/NIDDK NIH HHS/United States ; R01 HL123340/HL/NHLBI NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Animals ; Gastrointestinal Microbiome/*immunology ; Homeostasis/*immunology ; Humans ; *Intestines/immunology/virology ; Viruses/*immunology ; }, abstract = {The composition of the human microbiome is considered a major source of interindividual variation in immunity and, by extension, susceptibility to diseases. Intestinal bacteria have been the major focus of research. However, diverse communities of viruses that infect microbes and the animal host cohabitate the gastrointestinal tract and collectively constitute the gut virome. Although viruses are typically investigated as pathogens, recent studies highlight a relationship between the host and animal viruses in the gut that is more akin to host-microbiome interactions and includes both beneficial and detrimental outcomes for the host. These viruses are likely sources of immune variation, both locally and extraintestinally. In this review, we describe the components of the gut virome, in particular mammalian viruses, and their ability to modulate host responses during homeostasis and disease.}, }
@article {pmid30180541, year = {2018}, author = {Hill, AB and Beitelshees, M and Nayerhoda, R and Pfeifer, BA and Jones, CH}, title = {Engineering a Next-Generation Glycoconjugate-Like Streptococcus pneumoniae Vaccine.}, journal = {ACS infectious diseases}, volume = {4}, number = {11}, pages = {1553-1563}, pmid = {30180541}, issn = {2373-8227}, support = {R03 AI088485/AI/NIAID NIH HHS/United States ; R21 AI117309/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Antibodies, Bacterial/immunology ; Bacterial Capsules/*immunology ; Cell Line ; Female ; Glycoconjugates/chemistry/immunology ; Humans ; Immunization ; Injections, Subcutaneous ; Liposomes/*chemistry ; Male ; Mice ; Pneumococcal Infections/prevention &amp; control ; Pneumococcal Vaccines/chemistry/*immunology ; Polysaccharides, Bacterial/*immunology ; Serogroup ; Streptococcus pneumoniae ; Vaccines, Conjugate/chemistry/*immunology ; }, abstract = {We detail the development of a next-generation Streptococcus pneumoniae liposomal encapsulation of polysaccharides (LEPS) vaccine, with design characteristics geared toward best-in-class efficacy. The first generation LEPS vaccine, which contained 20 encapsulated pneumococcal capsular polysaccharides (CPSs) and two surface-displayed virulence-associated proteins (GlpO and PncO), enabling prophylactic potency against 70+ serotypes of Streptococcus pneumoniae (the causative agent of pneumococcal disease), was rationally redesigned for advanced clinical readiness and best-in-class coverage. In doing so, the virulent-specific GlpO protein antigen was removed from the final formulation due to off-target immunogenicity toward bacterial species within the human microbiome, while directed protection was maintained by increasing the dose of PncO from 17 to 68 μg. LEPS formulation parameters also readily facilitated an increase in CPS valency (to a total of 24) and systematic variation in protein-liposome attachment mechanisms in anticipation of clinical translation. An additional safety assessment study demonstrated that LEPS does not exhibit appreciable toxicological effects even when administered at ten times the effective dose. In summary, this new design offers the broadest, safest, and most-complete protection while maintaining desirable glycoconjugate-like features, positioning the LEPS vaccine platform for clinical success and a global health impact.}, }
@article {pmid30178250, year = {2018}, author = {Riscuta, G and Xi, D and Pierre-Victor, D and Starke-Reed, P and Khalsa, J and Duffy, L}, title = {Diet, Microbiome, and Epigenetics in the Era of Precision Medicine.}, journal = {Methods in molecular biology (Clifton, N.J.)}, volume = {1856}, number = {}, pages = {141-156}, doi = {10.1007/978-1-4939-8751-1_8}, pmid = {30178250}, issn = {1940-6029}, mesh = {Cell Transformation, Neoplastic/genetics/metabolism ; *Diet ; Disease Susceptibility ; Energy Metabolism ; *Epigenesis, Genetic ; Gene Expression Regulation ; Gene-Environment Interaction ; Host-Pathogen Interactions/genetics ; Humans ; *Microbiota ; Neoplasms/diagnosis/etiology/metabolism ; *Precision Medicine/methods ; }, abstract = {Precision medicine is a revolutionary approach to disease prevention and treatment that takes into account individual differences in lifestyle, environment, and biology. The US National Institutes of Health has recently launched The All of Us Research Program (2016) to extend precision medicine to all diseases by building a national research cohort of one million or more US participants. This review is limited to how the human microbiome factors into precision medicine from the applied aspect of preventing and managing cancer. The Precision Medicine Initiative was established in an effort to address particular characteristics of each person with the aim to increase the effectiveness of medical interventions in terms of prevention and treatment of multiple diseases including cancer. Many factors contribute to the response to an intervention. The microbiome and microbially produced metabolites are capable of epigenetic modulation of gene activity, and can influence the response through these mechanisms. The fact that diet has an impact on microbiome implies that it will also affect the epigenetic mechanisms involving microbiota. In this chapter, we review some major epigenetic mechanisms, notably DNA methylation, chromatin remodeling and histone modification, and noncoding RNA, implicated in cancer prevention and treatment. Several examples of how microbially produced metabolites from food influence cancer risk and treatment response through epigenetic mechanisms will be discussed. Some challenges include the limited understanding of how diet shapes the microbiome and how to best evaluate those changes since both, diet and the microbiota, exhibit daily and seasonal variations. Ongoing research seeks to understand the relationship between the human microbiome and multiple diseases including cancer.}, }
@article {pmid30177740, year = {2018}, author = {Lee, JYH and Monk, IR and Gonçalves da Silva, A and Seemann, T and Chua, KYL and Kearns, A and Hill, R and Woodford, N and Bartels, MD and Strommenger, B and Laurent, F and Dodémont, M and Deplano, A and Patel, R and Larsen, AR and Korman, TM and Stinear, TP and Howden, BP}, title = {Global spread of three multidrug-resistant lineages of Staphylococcus epidermidis.}, journal = {Nature microbiology}, volume = {3}, number = {10}, pages = {1175-1185}, pmid = {30177740}, issn = {2058-5276}, support = {R21 AI125870/AI/NIAID NIH HHS/United States ; }, mesh = {Anti-Bacterial Agents/*pharmacology ; Biological Coevolution ; Drug Resistance, Multiple, Bacterial/drug effects/*genetics ; Genes, Bacterial/genetics ; Genome, Bacterial/genetics ; Mutation ; Phylogeny ; Prevalence ; Rifampin/*pharmacology ; Staphylococcal Infections/*epidemiology/microbiology ; Staphylococcus epidermidis/classification/*drug effects/*genetics/isolation &amp; purification ; }, abstract = {Staphylococcus epidermidis is a conspicuous member of the human microbiome, widely present on healthy skin. Here we show that S. epidermidis has also evolved to become a formidable nosocomial pathogen. Using genomics, we reveal that three multidrug-resistant, hospital-adapted lineages of S. epidermidis (two ST2 and one ST23) have emerged in recent decades and spread globally. These lineages are resistant to rifampicin through acquisition of specific rpoB mutations that have become fixed in the populations. Analysis of isolates from 96 institutions in 24 countries identified dual D471E and I527M RpoB substitutions to be the most common cause of rifampicin resistance in S. epidermidis, accounting for 86.6% of mutations. Furthermore, we reveal that the D471E and I527M combination occurs almost exclusively in isolates from the ST2 and ST23 lineages. By breaching lineage-specific DNA methylation restriction modification barriers and then performing site-specific mutagenesis, we show that these rpoB mutations not only confer rifampicin resistance, but also reduce susceptibility to the last-line glycopeptide antibiotics, vancomycin and teicoplanin. Our study has uncovered the previously unrecognized international spread of a near pan-drug-resistant opportunistic pathogen, identifiable by a rifampicin-resistant phenotype. It is possible that hospital practices, such as antibiotic monotherapy utilizing rifampicin-impregnated medical devices, have driven the evolution of this organism, once trivialized as a contaminant, towards potentially incurable infections.}, }
@article {pmid30175072, year = {2018}, author = {Meng, S and Chen, B and Yang, J and Wang, J and Zhu, D and Meng, Q and Zhang, L}, title = {Study of Microbiomes in Aseptically Collected Samples of Human Breast Tissue Using Needle Biopsy and the Potential Role of in situ Tissue Microbiomes for Promoting Malignancy.}, journal = {Frontiers in oncology}, volume = {8}, number = {}, pages = {318}, pmid = {30175072}, issn = {2234-943X}, abstract = {Mounting evidence suggests that changes in microbiome are linked to development of cancer and its aggressiveness. Microbiome profiles in human breast tissue previously presumed to be sterile, have recently been characterized using high-throughput technologies. Recent findings of microbiome variation between benign and malignant disease provides a rationale for exploring microbiomes associated with cancer during tumor progression. We assessed microbiomes of aseptically collected human breast tissue samples in this study, using needle biopsy from patients with benign and malignant tumors of different histological grading, using 16S rRNA gene amplicon sequencing. This is consistent with previous studies, and our results identified distinct microbiome profiles in breast tissues from women with cancer as compared to women with benign breast disease in Chinese cohorts. The enriched microbial biomarkers in malignant tissue included genus Propionicimonas and families Micrococcaceae, Caulobacteraceae, Rhodobacteraceae, Nocardioidaceae, Methylobacteriaceae, which appeared to be ethno-specific. Further, we compared microbiome profiles in malignant tissues of three different histological grades. The relative abundance of family Bacteroidaceae decreased and that of genus Agrococcus increased with the development of malignancy. KEGG pathways inferred by PICRUSt showed that biotin and glycerophospholipid metabolism had significant differences in all three grades. Glycerophospholipid and ribosome biogenesis increased in grade III tissue as compared to grades I and II. Flavonoid biosynthesis significantly decreased in grade III tissue. The specific correlation of these potential microbial biomarkers and indicated pathways with advanced disease could have broad implications in the diagnosis and staging of breast cancer. Further large-cohort investigation of the breast cancer microbiome and its potential mechanism in breast cancer development are essential.}, }
@article {pmid30169121, year = {2018}, author = {Willis-Owen, SAG and Cookson, WOC and Moffatt, MF}, title = {The Genetics and Genomics of Asthma.}, journal = {Annual review of genomics and human genetics}, volume = {19}, number = {}, pages = {223-246}, doi = {10.1146/annurev-genom-083117-021651}, pmid = {30169121}, issn = {1545-293X}, mesh = {Asthma/*genetics ; Cloning, Molecular ; Epigenesis, Genetic ; Genetic Linkage ; *Genetic Predisposition to Disease ; Genome-Wide Association Study ; Humans ; Lung/metabolism ; Transcription, Genetic ; Transcriptome ; }, abstract = {Asthma is a common, clinically heterogeneous disease with strong evidence of heritability. Progress in defining the genetic underpinnings of asthma, however, has been slow and hampered by issues of inconsistency. Recent advances in the tools available for analysis-assaying transcription, sequence variation, and epigenetic marks on a genome-wide scale-have substantially altered this landscape. Applications of such approaches are consistent with heterogeneity at the level of causation and specify patterns of commonality with a wide range of alternative disease traits. Looking beyond the individual as the unit of study, advances in technology have also fostered comprehensive analysis of the human microbiome and its varied roles in health and disease. In this article, we consider the implications of these technological advances for our current understanding of the genetics and genomics of asthma.}, }
@article {pmid30159882, year = {2018}, author = {Skelly, E and Kapellas, K and Cooper, A and Weyrich, LS}, title = {Consequences of colonialism: A microbial perspective to contemporary Indigenous health.}, journal = {American journal of physical anthropology}, volume = {167}, number = {2}, pages = {423-437}, doi = {10.1002/ajpa.23637}, pmid = {30159882}, issn = {1096-8644}, support = {DE150101574//Australian Research Council/International ; }, mesh = {*Colonialism ; Diet/ethnology ; Dysbiosis/*ethnology ; Humans ; Indians, North American/*ethnology ; Microbiota/*physiology ; *Public Health ; Social Change ; }, abstract = {Nearly all Indigenous populations today suffer from worse health than their non-Indigenous counterparts, and despite interventions against known factors, this health "gap" has not improved. The human microbiome-the beneficial, diverse microbial communities that live on and within the human body-is a crucial component in developing and maintaining normal physiological health. Disrupting this ecosystem has repercussions for microbial functionality, and thus, human health. In this article, we propose that modern-day Indigenous population health may suffer from disrupted microbial ecosystems as a consequence of historical colonialism. Colonialism may have interrupted the established relationships between the environment, traditional lifeways, and microbiomes, altering the Indigenous microbiome with detrimental health consequences.}, }
@article {pmid30155556, year = {2019}, author = {Ma, ZS}, title = {Sketching the Human Microbiome Biogeography with DAR (Diversity-Area Relationship) Profiles.}, journal = {Microbial ecology}, volume = {77}, number = {3}, pages = {821-838}, pmid = {30155556}, issn = {1432-184X}, mesh = {Bacteria/classification/genetics/*isolation &amp; purification ; *Biodiversity ; Humans ; Metagenomics ; *Microbiota ; Models, Biological ; }, abstract = {SAR (species area relationship) is a classic ecological theory that has been extensively investigated and applied in the studies of global biogeography and biodiversity conservation in macro-ecology. It has also found important applications in microbial ecology in recent years thanks to the breakthroughs in metagenomic sequencing technology. Nevertheless, SAR has a serious limitation for practical applications-ignoring the species abundance and treating all species as equally abundant. This study aims to explore the biogeography discoveries of human microbiome over 18 sites of 5 major microbiome habitats, establish the baseline DAR (diversity-area scaling relationship) parameters, and perform comparisons with the classic SAR. The extension from SAR to DAR by adopting the Hill numbers as diversity measures not only overcomes the previously mentioned flaw of SAR but also allows for obtaining a series of important findings on the human microbiome biodiversity and biogeography. Specifically, two types of DAR models were built, the traditional power law (PL) and power law with exponential cutoff (PLEC), using comprehensive datasets from the HMP (human microbiome project). Furthermore, the biogeography "maps" for 18 human microbiome sites using their DAR profiles for assessing and predicting the diversity scaling across individuals, PDO profiles (pair-wise diversity overlap) for measuring diversity overlap (similarity), and MAD profile (for predicting the maximal accrual diversity in a population) were sketched out. The baseline biogeography maps for the healthy human microbiome diversity can offer guidelines for conserving human microbiome diversity and investigating the health implications of the human microbiome diversity and heterogeneity.}, }
@article {pmid30154777, year = {2018}, author = {Westerik, N and Reid, G and Sybesma, W and Kort, R}, title = {The Probiotic Lactobacillus rhamnosus for Alleviation of Helicobacter pylori-Associated Gastric Pathology in East Africa.}, journal = {Frontiers in microbiology}, volume = {9}, number = {}, pages = {1873}, pmid = {30154777}, issn = {1664-302X}, abstract = {The probiotic Lactobacillus rhamnosus GG (LGG) can play a role in establishing a harmless relationship with Helicobacter pylori and reduce gastric pathology in East African populations. H. pylori has the ability to inhabit the surface of the mucous layer of the human stomach and duodenum. In the developing world, an estimated 51% of the population is carrier of H. pylori, while in some Western countries these numbers dropped below 20%, which is probably associated with improved sanitation and smaller family sizes. Colonization by H. pylori can be followed by inflammation of the gastric mucus layer, and is a risk factor in the development of atrophic gastritis, peptic ulcers and gastric cancer. Notwithstanding the higher prevalence of H. pylori carriers in developing countries, no equal overall increase in gastric pathology is found. This has been attributed to a less pro-inflammatory immune response to H. pylori in African compared to Caucasian populations. In addition, a relatively low exposure to other risk factors in certain African populations may play a role, including the use of non-steroidal anti-inflammatory drugs, smoking, and diets without certain protective factors. A novel approach to the reduction of H. pylori associated gastric pathology is found in the administration of the probiotic bacterium Lactobacillus rhamnosus yoba 2012 (LRY), the generic variant of LGG. This gastro-intestinal isolate inhibits H. pylori by competition for substrate and binding sites as well as production of antimicrobial compounds such as lactic acid. In addition, it attenuates the host's H. pylori-induced apoptosis and inflammation responses and stimulates angiogenesis in the gastric and duodenal epithelium. The probiotic LRY is not able to eradicate H. pylori completely, but its co-supplementation in antibiotic eradication therapy has been shown to relieve side effects of this therapy. In Uganda, unlike other African countries, gastric pathology is relatively common, presumably resulting from the lack of dietary protective factors in the traditional diet. Supplementation with LRY through local production of probiotic yogurt, could be a solution to establish a harmless relationship with H. pylori and reduce gastric pathology and subsequent eradication therapy treatment.}, }
@article {pmid30154767, year = {2018}, author = {Kho, ZY and Lal, SK}, title = {The Human Gut Microbiome - A Potential Controller of Wellness and Disease.}, journal = {Frontiers in microbiology}, volume = {9}, number = {}, pages = {1835}, pmid = {30154767}, issn = {1664-302X}, abstract = {Interest toward the human microbiome, particularly gut microbiome has flourished in recent decades owing to the rapidly advancing sequence-based screening and humanized gnotobiotic model in interrogating the dynamic operations of commensal microbiota. Although this field is still at a very preliminary stage, whereby the functional properties of the complex gut microbiome remain less understood, several promising findings have been documented and exhibit great potential toward revolutionizing disease etiology and medical treatments. In this review, the interactions between gut microbiota and the host have been focused on, to provide an overview of the role of gut microbiota and their unique metabolites in conferring host protection against invading pathogen, regulation of diverse host physiological functions including metabolism, development and homeostasis of immunity and the nervous system. We elaborate on how gut microbial imbalance (dysbiosis) may lead to dysfunction of host machineries, thereby contributing to pathogenesis and/or progression toward a broad spectrum of diseases. Some of the most notable diseases namely Clostridium difficile infection (infectious disease), inflammatory bowel disease (intestinal immune-mediated disease), celiac disease (multisystemic autoimmune disorder), obesity (metabolic disease), colorectal cancer, and autism spectrum disorder (neuropsychiatric disorder) have been discussed and delineated along with recent findings. Novel therapies derived from microbiome studies such as fecal microbiota transplantation, probiotic and prebiotics to target associated diseases have been reviewed to introduce the idea of how certain disease symptoms can be ameliorated through dysbiosis correction, thus revealing a new scientific approach toward disease treatment. Toward the end of this review, several research gaps and limitations have been described along with suggested future studies to overcome the current research lacunae. Despite the ongoing debate on whether gut microbiome plays a role in the above-mentioned diseases, we have in this review, gathered evidence showing a potentially far more complex link beyond the unidirectional cause-and-effect relationship between them.}, }
@article {pmid30150778, year = {2018}, author = {Xu, W and Luo, Z and Alekseyenko, AV and Martin, L and Wan, Z and Ling, B and Qin, Z and Heath, SL and Maas, K and Cong, X and Jiang, W}, title = {Distinct systemic microbiome and microbial translocation are associated with plasma level of anti-CD4 autoantibody in HIV infection.}, journal = {Scientific reports}, volume = {8}, number = {1}, pages = {12863}, pmid = {30150778}, issn = {2045-2322}, support = {P30 AI027767/AI/NIAID NIH HHS/United States ; R01 AI128864/AI/NIAID NIH HHS/United States ; U54 GM104940/GM/NIGMS NIH HHS/United States ; R01 AI093307/AI/NIAID NIH HHS/United States ; P50 AR070591/AR/NIAMS NIH HHS/United States ; R01 NS104016/NS/NINDS NIH HHS/United States ; R01 NR016928/NR/NINR NIH HHS/United States ; U54 CA210962/CA/NCI NIH HHS/United States ; R01 AI091526/AI/NIAID NIH HHS/United States ; P51 OD011104/OD/NIH HHS/United States ; U54 CA210963/CA/NCI NIH HHS/United States ; R01 CA228166/CA/NCI NIH HHS/United States ; R01 LM012517/LM/NLM NIH HHS/United States ; K23 NR014674/NR/NINR NIH HHS/United States ; R01 CA164964/CA/NCI NIH HHS/United States ; }, mesh = {Adult ; Autoantibodies/blood/*immunology ; Autoantigens/*immunology ; Bacterial Translocation ; CD4 Lymphocyte Count ; CD4-Positive T-Lymphocytes/*immunology ; CD8-Positive T-Lymphocytes/immunology/metabolism ; Case-Control Studies ; Female ; HIV Infections/*immunology/virology ; HIV-1/*immunology ; Humans ; Male ; *Microbiota/immunology ; Middle Aged ; }, abstract = {Microbial signals have been linked to autoantibody induction. Recently, we found that purified anti-CD4 autoantibodies from the plasma of chronic HIV-1-infected patients under viral-suppressed antiretroviral therapy (ART) play a pathologic role in poor CD4+ T cell recovery. The purpose of the study was to investigate the association of systemic microbiome and anti-CD4 autoantibody production in HIV. Plasma microbiome from 12 healthy controls and 22 HIV-infected subjects under viral-suppressed ART were analyzed by MiSeq sequencing. Plasma level of autoantibodies and microbial translocation (LPS, total bacterial 16S rDNA, soluble CD14, and LPS binding protein) were analyzed by ELISA, limulus amebocyte assay, and qPCR. We found that plasma level of anti-CD4 IgGs but not anti-CD8 IgGs was increased in HIV+ subjects compared to healthy controls. HIV+ subjects with plasma anti-CD4 IgG > 50 ng/mL (high) had reduced microbial diversity compared to HIV+ subjects with anti-CD4 IgG ≤ 50 ng/mL (low). Moreover, plasma anti-CD4 IgG level was associated with elevated microbial translocation and reduced microbial diversity in HIV+ subjects. The Alphaproteobacteria class was significantly enriched in HIV+ subjects with low anti-CD4 IgG compared to patients with high anti-CD4 IgG even after controlling for false discovery rate (FDR). The microbial components were different from the phylum to genus level in HIV+ subjects with high anti-CD4 IgGs compared to the other two groups, but these differences were not significant after controlling for FDR. These results suggest that systemic microbial translocation and microbiome may associate with anti-CD4 autoantibody production in ART-treated HIV disease.}, }
@article {pmid30146515, year = {2018}, author = {Suda, W and Ogata, Y and Nishijima, S}, title = {[Analysis of human microbiome using NGS.].}, journal = {Clinical calcium}, volume = {28}, number = {9}, pages = {1274-1281}, pmid = {30146515}, issn = {0917-5857}, mesh = {DNA ; *High-Throughput Nucleotide Sequencing ; Humans ; *Microbiota ; RNA, Ribosomal, 16S ; Sequence Analysis, DNA ; }, abstract = {Recently, next generation sequencers(NGS)became prevalent and enable us possible to comprehensively analyze the entire human microbiome community structures including difficult-to-culture microbes. In this review, we introduce the NGS-based analytical methods of human microbiome, called "meta-16S analysis" and "metagenomic analysis", then show several fundamental data basing these analyses. Furthermore, we also introduce the importance of database improvement used for analysis and the DNA preparation method from human samples.}, }
@article {pmid30144429, year = {2018}, author = {Friedman, ES and Li, Y and Shen, TD and Jiang, J and Chau, L and Adorini, L and Babakhani, F and Edwards, J and Shapiro, D and Zhao, C and Carr, RM and Bittinger, K and Li, H and Wu, GD}, title = {FXR-Dependent Modulation of the Human Small Intestinal Microbiome by the Bile Acid Derivative Obeticholic Acid.}, journal = {Gastroenterology}, volume = {155}, number = {6}, pages = {1741-1752.e5}, pmid = {30144429}, issn = {1528-0012}, support = {R01 AA026302/AA/NIAAA NIH HHS/United States ; K08 DK106457/DK/NIDDK NIH HHS/United States ; R01 GM123056/GM/NIGMS NIH HHS/United States ; K08 AA021424/AA/NIAAA NIH HHS/United States ; P30 DK050306/DK/NIDDK NIH HHS/United States ; P30 DK019525/DK/NIDDK NIH HHS/United States ; }, mesh = {Adult ; Animals ; Bile Acids and Salts/*physiology ; Chenodeoxycholic Acid/*analogs &amp; derivatives/pharmacokinetics ; Female ; Gastrointestinal Microbiome/*drug effects ; Healthy Volunteers ; Humans ; Intestine, Small/*microbiology ; Male ; Mice ; Mice, Inbred C57BL ; Receptors, Cytoplasmic and Nuclear/*physiology ; }, abstract = {BACKGROUND &amp; AIMS: Intestinal bacteria can modify the composition of bile acids and bile acids, which are regulated by the farnesoid X receptor, affect the survival and growth of gut bacteria. We studied the effects of obeticholic acid (OCA), a bile acid analogue and farnesoid X receptor agonist, on the intestinal microbiomes of humans and mice.<br><br>METHODS: We performed a phase I study in 24 healthy volunteers given OCA (5, 10, or 25 mg/d for 17 days). Fecal and plasma specimens were collected at baseline (day 0) and on days 17 (end of dosing) and 37 (end of study). The fecal specimens were analyzed by shotgun meta-genomic sequencing. A Uniref90 high-stringency genomic analysis was used to assign specific genes to the taxonomic signature of bacteria whose abundance was associated with OCA. Male C57BL/6 mice were gavage fed daily with water, vehicle, or OCA (10 mg/kg) for 2 weeks. Small intestine luminal contents were collected by flushing with saline and fecal pellets were collected at baseline and day 14. Mouse samples were analyzed by 16S-tagged sequencing. Culture experiments were performed to determine the taxonomic-specific effects of bile acids and OCA on bacterial growth.<br><br>RESULTS: Suppression of endogenous bile acid synthesis by OCA in subjects led to a reversible induction of gram-positive bacteria that are found in the small intestine and are components of the diet and oral microbiota. We found that bile acids decreased proliferation of these bacteria in minimum inhibitory concentration assays. In these organisms, there was an increase in the representation of microbial genomic pathways involved in DNA synthesis and amino acid metabolism with OCA treatment of subjects. Consistent with these findings, mice fed OCA had lower endogenous bile acid levels and an increased proportion of Firmicutes, specifically in the small intestine, compared with mice fed water or vehicle.<br><br>CONCLUSIONS: In studying the effects of OCA in humans and mice, we found evidence for interactions between bile acids and features of the small intestinal microbiome. These findings indicate that farnesoid X receptor activation alters the intestinal microbiota and could provide opportunities for microbiome biomarker discovery or new approaches to engineering the human microbiome. ClinicalTrials.gov, NCT01933503.}, }
@article {pmid30135504, year = {2018}, author = {Hoen, AG and Madan, JC and Li, Z and Coker, M and Lundgren, SN and Morrison, HG and Palys, T and Jackson, BP and Sogin, ML and Cottingham, KL and Karagas, MR}, title = {Sex-specific associations of infants' gut microbiome with arsenic exposure in a US population.}, journal = {Scientific reports}, volume = {8}, number = {1}, pages = {12627}, pmid = {30135504}, issn = {2045-2322}, support = {RD-83459901//U.S. Environmental Protection Agency (EPA)/International ; P01ES022832//U.S. Department of Health &amp; Human Services | NIH | National Institute of Environmental Health Sciences (NIEHS)/International ; UH3 OD023275/OD/NIH HHS/United States ; R01LM012723//U.S. Department of Health &amp; Human Services | NIH | U.S. National Library of Medicine (NLM)/International ; R01 GM123014/GM/NIGMS NIH HHS/United States ; P20GM104416//U.S. Department of Health &amp; Human Services | NIH | National Institute of General Medical Sciences (NIGMS)/International ; R01 LM012723/LM/NLM NIH HHS/United States ; K01 LM011985/LM/NLM NIH HHS/United States ; RD-83544201//U.S. Environmental Protection Agency (EPA)/International ; P20 ES018175/ES/NIEHS NIH HHS/United States ; R01GM123014//U.S. Department of Health &amp; Human Services | NIH | National Institute of General Medical Sciences (NIGMS)/International ; P01 ES022832/ES/NIEHS NIH HHS/United States ; UG3 OD023275/OD/NIH HHS/United States ; P20 GM104416/GM/NIGMS NIH HHS/United States ; }, mesh = {Arsenic/*adverse effects/analysis/urine ; Bacteria/genetics ; Breast Feeding ; Cohort Studies ; Feces/microbiology ; Female ; Gastrointestinal Microbiome/*drug effects ; Humans ; Infant ; Infant, Newborn ; Male ; Microbiota ; Prospective Studies ; RNA, Ribosomal, 16S/genetics ; Sex Factors ; United States/epidemiology ; }, abstract = {Arsenic is a ubiquitous environmental toxicant with antimicrobial properties that can be found in food and drinking water. The influence of arsenic exposure on the composition of the human microbiome in US populations remains unknown, particularly during the vulnerable infant period. We investigated the relationship between arsenic exposure and gut microbiome composition in 204 infants prospectively followed as part of the New Hampshire Birth Cohort Study. Infant urine was analyzed for total arsenic concentration using inductively coupled plasma mass spectrometry. Stool microbiome composition was determined using sequencing of the bacterial 16S rRNA gene. Infant urinary arsenic related to gut microbiome composition at 6 weeks of life (p = 0.05, adjusted for infant feeding type and urine specific gravity). Eight genera, six within the phylum Firmicutes, were enriched with higher arsenic exposure. Fifteen genera were negatively associated with urinary arsenic concentration, including Bacteroides and Bifidobacterium. Upon stratification by both sex and feeding method, we found detectable associations among formula-fed males (p = 0.008), but not other groups (p > 0.05 for formula-fed females and for breastfed males and females). Our findings from a US population indicate that even moderate arsenic exposure may have meaningful, sex-specific effects on the gut microbiome during a critical window of infant development.}, }
@article {pmid30131772, year = {2018}, author = {Ma, ZS and Li, L and Li, W}, title = {Assessing and Interpreting the Within-Body Biogeography of Human Microbiome Diversity.}, journal = {Frontiers in microbiology}, volume = {9}, number = {}, pages = {1619}, pmid = {30131772}, issn = {1664-302X}, abstract = {A human body hosts a relatively independent microbiome including five major regional biomes (i.e., airway, oral, gut, skin, and urogenital). Each of them may possess different regional characteristics with important implications to our health and diseases (i.e., so-termed microbiome associated diseases). Nevertheless, these regional microbiomes are connected with each other through diffusions and migrations. Here, we investigate the within-body (intra-individual) distribution feature of microbiome diversity via diversity area relationship (DAR) modeling, which, to the best of our knowledge, has not been systematically studied previously. We utilized the Hill numbers for measuring alpha and beta-diversities and built 1,200 within-body DAR models with to date the most comprehensive human microbiome datasets of 18 sites from the human microbiome project (HMP) cohort. We established the intra-DAR profile (z-q pattern: the diversity scaling parameter z of the power law (PL) at diversity order q = 0-3), intra-PDO (pair-wise diversity overlap) profile (g-q), and intra-MAD (maximal accrual diversity) profile (D max-q) for the within-body biogeography of the human microbiome. These profiles constitute the "maps" of the within-body biogeography, and offer important insights on the within-body distribution of the human microbiome. Furthermore, we investigated the heterogeneity among individuals in their biogeography parameters and found that there is not an "average Joe" that can represent majority of individuals in a cohort or population. For example, we found that most individuals in the HMP cohort have relatively lower maximal accrual diversity (MAD) or in the "long tail" of the so-termed power law distribution. In the meantime, there are a small number of individuals in the cohort who possess disproportionally higher MAD values. These findings may have important implications for personalized medicine of the human microbiome associated diseases in practice, besides their theoretical significance in microbiome research such as establishing the baseline for the conservation of human microbiome.}, }
@article {pmid30129129, year = {2018}, author = {Heerema-McKenney, A}, title = {Defense and infection of the human placenta.}, journal = {APMIS : acta pathologica, microbiologica, et immunologica Scandinavica}, volume = {126}, number = {7}, pages = {570-588}, doi = {10.1111/apm.12847}, pmid = {30129129}, issn = {1600-0463}, mesh = {Communicable Diseases/*pathology ; Female ; Humans ; Placenta/*immunology/*pathology ; Placenta Diseases/*pathology ; Pregnancy ; Pregnancy Complications, Infectious/*pathology ; }, abstract = {The placenta functions as a shield against infection of the fetus. The innate and adaptive immune defenses of the developing fetus are poorly equipped to fight infections. Infection by bacteria, viruses, and protozoa may cause infertility, spontaneous abortion, stillbirth, growth retardation, anomalies of development, premature delivery, neonatal morbidity, and mortality. However, appreciation of the human microbiome and host cell-microbe interactions must be taken into consideration as we try to determine what interactions are pathologic. Infection is typically recognized histologically by the presence of inflammation. Yet, several factors make comparison of the placenta to other human organs difficult. The placenta comprises tissues from two persons, complicating the role of the immune system. The placenta is a temporary organ. It must be eventually expelled; the processes leading to partuition involve maternal inflammation. What is normal or pathologic may be a function of timing or extent of the process. We now must consider whether bacteria, and even some viruses, are useful commensals or pathogens. Still, recognizing infection of the placenta is one of the most important contributions placental pathologic examination can give to care of the mother and neonate. This review provides a brief overview of placental defense against infection, consideration of the placental microbiome, routes of infection, and the histopathology of amniotic fluid infection and TORCH infections.}, }
@article {pmid30129002, year = {2018}, author = {Lin, J and Kimura, BY and Oikarinen, S and Nykter, M}, title = {Bioinformatics Assembling and Assessment of Novel Coxsackievirus B1 Genome.}, journal = {Methods in molecular biology (Clifton, N.J.)}, volume = {1838}, number = {}, pages = {261-272}, doi = {10.1007/978-1-4939-8682-8_18}, pmid = {30129002}, issn = {1940-6029}, mesh = {*Computational Biology/methods ; Enterovirus B, Human/*genetics ; *Genome, Viral ; *Genomics/methods ; Humans ; Metagenome ; Metagenomics/methods/standards ; Quality Control ; }, abstract = {The human microbiome project via application of metagenomic next-generation sequencing techniques has found surprising large and diverse amounts of microbial sequences across different body sites. There is a wave of investigators studying autoimmune related diseases designing from birth case and control studies to elucidate microbial associations and potential direct triggers. Sequencing analysis, considered big data as it typically includes millions of reads, is challenging but particularly demanding and complex is virome profiling due to its lack of pan-viral genomic signature. Impressively thousands of virus complete genomes have been deposited and these high-quality references are core components of virus profiling pipelines and databases. Still it is commonly known that most viral sequences do not map to known viruses. Moreover human viruses, particularly RNA groups, are notoriously heterogeneous due to high mutation rates. Here, we present the related assembling challenges and a series of bioinformatics steps that were applied in the construction of the complete consensus genome of a novel clinical isolate of Coxsackievirus B1. We further demonstrate our effort in calling mutations between prototype Coxsackievirus B1 sequence from GenBank and serial clinical isolate genome grown in cell culture.}, }
@article {pmid30124405, year = {2018}, author = {Dubourg, G and Baron, S and Cadoret, F and Couderc, C and Fournier, PE and Lagier, JC and Raoult, D}, title = {From Culturomics to Clinical Microbiology and Forward.}, journal = {Emerging infectious diseases}, volume = {24}, number = {9}, pages = {1683-1690}, pmid = {30124405}, issn = {1080-6059}, mesh = {Bacteria/classification/genetics/*isolation &amp; purification ; Bacterial Typing Techniques ; Communicable Disease Control ; DNA, Bacterial ; France/epidemiology ; Gram-Negative Bacterial Infections/*epidemiology/microbiology/prevention &amp; control ; Gram-Positive Bacterial Infections/*epidemiology/microbiology/prevention &amp; control ; Humans ; Sensitivity and Specificity ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization ; }, abstract = {Culturomics has permitted discovery of hundreds of new bacterial species isolated from the human microbiome. Profiles generated by using matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry have been added to the mass spectrometer database used in clinical microbiology laboratories. We retrospectively collected raw data from MALDI-TOF mass spectrometry used routinely in our laboratory in Marseille, France, during January 2012-March 2018 and analyzed 16S rDNA sequencing results from misidentified strains. During the study period, 744 species were identified from clinical specimens, of which 21 were species first isolated from culturomics. This collection involved 105 clinical specimens, accounting for 98 patients. In 64 cases, isolation of the bacteria was considered clinically relevant. MALDI-TOF mass spectrometry was able to identify the species in 95.2% of the 105 specimens. While contributing to the extension of the bacterial repertoire associated with humans, culturomics studies also enlarge the spectrum of prokaryotes involved in infectious diseases.}, }
@article {pmid30111623, year = {2018}, author = {Bisanz, JE and Spanogiannopoulos, P and Pieper, LM and Bustion, AE and Turnbaugh, PJ}, title = {How to Determine the Role of the Microbiome in Drug Disposition.}, journal = {Drug metabolism and disposition: the biological fate of chemicals}, volume = {46}, number = {11}, pages = {1588-1595}, pmid = {30111623}, issn = {1521-009X}, support = {P30 DK098722/DK/NIDDK NIH HHS/United States ; R01 HL122593/HL/NHLBI NIH HHS/United States ; T32 GM007175/GM/NIGMS NIH HHS/United States ; //CIHR/Canada ; }, mesh = {Animals ; Drug Discovery/methods ; Gastrointestinal Microbiome/*physiology ; Humans ; Inactivation, Metabolic/physiology ; Pharmaceutical Preparations/*metabolism ; }, abstract = {With a paradigm shift occurring in health care toward personalized and precision medicine, understanding the numerous environmental factors that impact drug disposition is of paramount importance. The highly diverse and variant nature of the human microbiome is now recognized as a factor driving interindividual variation in therapeutic outcomes. The purpose of this review is to provide a practical guide on methodology that can be applied to study the effects of microbes on the absorption, distribution, metabolism, and excretion of drugs. We also highlight recent examples of how these methods have been successfully applied to help build the basis for researching the intersection of the microbiome and pharmacology. Although in vitro and in vivo preclinical models are highlighted, these methods are also relevant in late-phase drug development or even as a part of routine after-market surveillance. These approaches will aid in filling major knowledge gaps for both current and upcoming therapeutics with the long-term goal of achieving a new type of knowledge-based medicine that integrates data on the host and the microbiome.}, }
@article {pmid30110974, year = {2018}, author = {Fernández, MF and Reina-Pérez, I and Astorga, JM and Rodríguez-Carrillo, A and Plaza-Díaz, J and Fontana, L}, title = {Breast Cancer and Its Relationship with the Microbiota.}, journal = {International journal of environmental research and public health}, volume = {15}, number = {8}, pages = {}, pmid = {30110974}, issn = {1660-4601}, mesh = {Breast Neoplasms/*microbiology ; Dysbiosis ; Estrogens/biosynthesis ; Female ; Gastrointestinal Microbiome/physiology ; Humans ; Microbiota/*physiology ; }, abstract = {The microorganisms that live symbiotically in human beings are increasingly recognized as important players in health and disease. The largest collection of these microorganisms is found in the gastrointestinal tract. Microbial composition reflects both genetic and lifestyle variables of the host. This microbiota is in a dynamic balance with the host, exerting local and distant effects. Microbial perturbation (dysbiosis) could contribute to the risk of developing health problems. Various bacterial genes capable of producing estrogen-metabolizing enzymes have been identified. Accordingly, gut microbiota is capable of modulating estrogen serum levels. Conversely, estrogen-like compounds may promote the proliferation of certain species of bacteria. Therefore, a crosstalk between microbiota and both endogenous hormones and estrogen-like compounds might synergize to provide protection from disease but also to increase the risk of developing hormone-related diseases. Recent research suggests that the microbiota of women with breast cancer differs from that of healthy women, indicating that certain bacteria may be associated with cancer development and with different responses to therapy. In this review, we discuss recent knowledge about the microbiome and breast cancer, identifying specific characteristics of the human microbiome that may serve to develop novel approaches for risk assessment, prevention and treatment for this disease.}, }
@article {pmid30108246, year = {2018}, author = {Bučević Popović, V and Šitum, M and Chow, CT and Chan, LS and Roje, B and Terzić, J}, title = {The urinary microbiome associated with bladder cancer.}, journal = {Scientific reports}, volume = {8}, number = {1}, pages = {12157}, pmid = {30108246}, issn = {2045-2322}, support = {IP-2014-09-1904//Hrvatska Zaklada za Znanost (Croatian Science Foundation)/International ; }, mesh = {Aged ; Aged, 80 and over ; Bacteria/genetics/isolation &amp; purification ; Case-Control Studies ; DNA, Bacterial/isolation &amp; purification ; Healthy Volunteers ; High-Throughput Nucleotide Sequencing ; Humans ; Male ; *Microbiota ; Middle Aged ; RNA, Ribosomal, 16S/genetics ; Urinary Bladder/*microbiology/pathology ; Urinary Bladder Neoplasms/*microbiology/pathology/urine ; Urine/*microbiology ; }, abstract = {Recent findings suggest that human microbiome can influence the development of cancer, but the role of microorganisms in bladder cancer pathogenesis has not been explored yet. The aim of this study was to characterize and compare the urinary microbiome of bladder cancer patients with those of healthy controls. Bacterial communities present in urine specimens collected from 12 male patients diagnosed with bladder cancer, and from 11 healthy, age-matched individuals were analysed using 16S sequencing. Our results show that the most abundant phylum in both groups was Firmicutes, followed by Actinobacteria, Bacteroidetes and Proteobacteria. While microbial diversity and overall microbiome composition were not significantly different between groups, we could identify operational taxonomic units (OTUs) that were more abundant in either group. Among those that were significantly enriched in the bladder cancer group, we identified an OTU belonging to genus Fusobacterium, a possible protumorigenic pathogen. In an independent sample of 42 bladder cancer tissues, 11 had Fusobacterium nucleatum sequences detected by PCR. Three OTUs from genera Veillonella, Streptococcus and Corynebacterium were more abundant in healthy urines. However, due to the limited number of participants additional studies are needed to determine if urinary microbiome is associated with bladder cancer.}, }
@article {pmid30099552, year = {2019}, author = {Bastiaanssen, TFS and Cowan, CSM and Claesson, MJ and Dinan, TG and Cryan, JF}, title = {Making Sense of … the Microbiome in Psychiatry.}, journal = {The international journal of neuropsychopharmacology}, volume = {22}, number = {1}, pages = {37-52}, pmid = {30099552}, issn = {1469-5111}, mesh = {Animals ; Brain/physiology/physiopathology ; *Gastrointestinal Microbiome ; Humans ; Mental Disorders/*microbiology/physiopathology ; Nervous System Diseases/*microbiology/physiopathology ; }, abstract = {Microorganisms can be found almost anywhere, including in and on the human body. The collection of microorganisms associated with a certain location is called a microbiota, with its collective genetic material referred to as the microbiome. The largest population of microorganisms on the human body resides in the gastrointestinal tract; thus, it is not surprising that the most investigated human microbiome is the human gut microbiome. On average, the gut hosts microbes from more than 60 genera and contains more cells than the human body. The human gut microbiome has been shown to influence many aspects of host health, including more recently the brain.Several modes of interaction between the gut and the brain have been discovered, including via the synthesis of metabolites and neurotransmitters, activation of the vagus nerve, and activation of the immune system. A growing body of work is implicating the microbiome in a variety of psychological processes and neuropsychiatric disorders. These include mood and anxiety disorders, neurodevelopmental disorders such as autism spectrum disorder and schizophrenia, and even neurodegenerative disorders such as Alzheimer's and Parkinson's diseases. Moreover, it is probable that most psychotropic medications have an impact on the microbiome.Here, an overview will be provided for the bidirectional role of the microbiome in brain health, age-associated cognitive decline, and neurological and psychiatric disorders. Furthermore, a primer on the common microbiological and bioinformatics techniques used to interrogate the microbiome will be provided. This review is meant to equip the reader with a primer to this exciting research area that is permeating all areas of biological psychiatry research.}, }
@article {pmid30098679, year = {2018}, author = {Kroon, SJ and Ravel, J and Huston, WM}, title = {Cervicovaginal microbiota, women's health, and reproductive outcomes.}, journal = {Fertility and sterility}, volume = {110}, number = {3}, pages = {327-336}, doi = {10.1016/j.fertnstert.2018.06.036}, pmid = {30098679}, issn = {1556-5653}, support = {R01 NR014826/NR/NINR NIH HHS/United States ; R01 NR014784/NR/NINR NIH HHS/United States ; R01 AI116799/AI/NIAID NIH HHS/United States ; }, mesh = {Cervix Uteri/microbiology/*physiology ; Dysbiosis/complications/diagnosis/microbiology ; Female ; Humans ; Infertility, Female/diagnosis/etiology/microbiology ; Lactobacillus/isolation &amp; purification/physiology ; Microbiota/*physiology ; Pregnancy ; Reproduction/*physiology ; Vagina/microbiology/*physiology ; *Women's Health/trends ; }, abstract = {The human microbiome project has shown a remarkable diversity of microbial ecology within the human body. The vaginal microbiota is unique in that in many women it is most often dominated by Lactobacillus species. However, in some women it lacks Lactobacillus spp. and is comprised of a wide array of strict and facultative anaerobes, a state that broadly correlates with increased risk for infection, disease, and poor reproductive and obstetric outcomes. Interestingly, the level of protection against infection can also vary by species and strains of Lactobacillus, and some species although dominant are not always optimal. This factors into the risk of contracting sexually transmitted infections and possibly influences the occurrence of resultant adverse reproductive outcomes such as tubal factor infertility. The composition and function of the vaginal microbiota appear to play an important role in pregnancy and fertility treatment outcomes and future research in this field will shed further translational mechanistic understanding onto the interplay of the vaginal microbiota with women's health and reproduction.}, }
@article {pmid30082394, year = {2018}, author = {Shrivastava, A and Patel, VK and Tang, Y and Yost, SC and Dewhirst, FE and Berg, HC}, title = {Cargo transport shapes the spatial organization of a microbial community.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {34}, pages = {8633-8638}, pmid = {30082394}, issn = {1091-6490}, support = {K99 DE026826/DE/NIDCR NIH HHS/United States ; R01 AI016478/AI/NIAID NIH HHS/United States ; R37 DE016937/DE/NIDCR NIH HHS/United States ; }, mesh = {Capnocytophaga/*physiology ; Humans ; Microbial Consortia/*physiology ; Microbiota/*physiology ; Mouth/*microbiology ; }, abstract = {The human microbiome is an assemblage of diverse bacteria that interact with one another to form communities. Bacteria in a given community are arranged in a 3D matrix with many degrees of freedom. Snapshots of the community display well-defined structures, but the steps required for their assembly are not understood. Here, we show that this construction is carried out with the help of gliding bacteria. Gliding is defined as the motion of cells over a solid or semisolid surface without the necessity of growth or the aid of pili or flagella. Genomic analysis suggests that gliding bacteria are present in human microbial communities. We focus on Capnocytophaga gingivalis, which is present in abundance in the human oral microbiome. Tracking of fluorescently labeled single cells and of gas bubbles carried by fluid flow shows that swarms of C. gingivalis are layered, with cells in the upper layers moving more rapidly than those in the lower layers. Thus, cells also glide on top of one another. Cells of nonmotile bacterial species attach to the surface of C. gingivalis and are propelled as cargo. The cargo cell moves along the length of a C. gingivalis cell, looping from one pole to the other. Multicolor fluorescent spectral imaging of cells of different live but nonmotile bacterial species reveals their long-range transport in a polymicrobial community. A swarm of C. gingivalis transports some nonmotile bacterial species more efficiently than others and helps to shape the spatial organization of a polymicrobial community.}, }
@article {pmid30078138, year = {2018}, author = {Martin, TC and Visconti, A and Spector, TD and Falchi, M}, title = {Conducting metagenomic studies in microbiology and clinical research.}, journal = {Applied microbiology and biotechnology}, volume = {102}, number = {20}, pages = {8629-8646}, pmid = {30078138}, issn = {1432-0614}, support = {//Wellcome Trust/United Kingdom ; }, mesh = {Bacteria/classification/genetics/*isolation &amp; purification ; Bacterial Infections/*microbiology ; Clinical Protocols ; High-Throughput Nucleotide Sequencing ; Humans ; *Metagenomics/methods ; Microbiology ; }, abstract = {Owing to the increased cost-effectiveness of high-throughput technologies, the number of studies focusing on the human microbiome and its connections to human health and disease has recently surged. However, best practices in microbiology and clinical research have yet to be clearly established. Here, we present an overview of the challenges and opportunities involved in conducting a metagenomic study, with a particular focus on data processing and analytical methods.}, }
@article {pmid30074108, year = {2019}, author = {Bicknell, B and Liebert, A and Johnstone, D and Kiat, H}, title = {Photobiomodulation of the microbiome: implications for metabolic and inflammatory diseases.}, journal = {Lasers in medical science}, volume = {34}, number = {2}, pages = {317-327}, pmid = {30074108}, issn = {1435-604X}, mesh = {Animals ; Feces/microbiology ; Humans ; Inflammation/*radiotherapy ; *Low-Level Light Therapy ; Male ; Metabolic Diseases/*radiotherapy ; Mice, Inbred BALB C ; Microbiota/genetics/*radiation effects ; Phylogeny ; Principal Component Analysis ; RNA, Ribosomal, 16S/genetics ; }, abstract = {The human microbiome is intimately associated with human health, with a role in obesity, metabolic diseases such as type 2 diabetes, and divergent diseases such as cardiovascular and neurodegenerative diseases. The microbiome can be changed by diet, probiotics, and faecal transplants, which has flow-on effects to health outcomes. Photobiomodulation has a therapeutic effect on inflammation and neurological disorders (amongst others) and has been reported to influence metabolic disorders and obesity. The aim of this study was to examine the possibility that PBM could influence the microbiome of mice. Mice had their abdomen irradiated with red (660 nm) or infrared (808 nm) low-level laser, either as single or multiple doses, over a 2-week period. Genomic DNA extracted from faecal pellets was pyrosequenced for the 16S rRNA gene. There was a significant (p < 0.05) difference in microbial diversity between PBM- and sham-treated mice. One genus of bacterium (Allobaculum) significantly increased (p < 0.001) after infrared (but not red light) PBM by day 14. Despite being a preliminary trial with small experimental numbers, we have demonstrated for the first time that PBM can alter microbiome diversity in healthy mice and increase numbers of Allobaculum, a bacterium associated with a healthy microbiome. This change is most probably a result of PBMt affecting the host, which in turn influenced the microbiome. If this is confirmed in humans, the possibility exists for PBMt to be used as an adjunct therapy in treatment of obesity and other lifestyle-related disorders, as well as cardiovascular and neurodegenerative diseases. The clinical implications of altering the microbiome using PBM warrants further investigation.}, }
@article {pmid30071492, year = {2018}, author = {Hanssen, EN and Liland, KH and Gill, P and Snipen, L}, title = {Optimizing body fluid recognition from microbial taxonomic profiles.}, journal = {Forensic science international. Genetics}, volume = {37}, number = {}, pages = {13-20}, doi = {10.1016/j.fsigen.2018.07.012}, pmid = {30071492}, issn = {1878-0326}, mesh = {Bacteria/*genetics ; Discriminant Analysis ; Feces/*microbiology ; Female ; Forensic Genetics/methods ; High-Throughput Nucleotide Sequencing ; Humans ; Least-Squares Analysis ; Microbiota ; Mouth/*microbiology ; Nasal Cavity/*microbiology ; *RNA, Ribosomal, 16S ; Sensitivity and Specificity ; Sequence Analysis, DNA ; Skin/*microbiology ; Vagina/*microbiology ; }, abstract = {In forensics the DNA-profile is used to identify the person who left a biological trace, but information on body fluid can also be essential in the evidence evaluation process. Microbial composition data could potentially be used for body fluid recognition as an improved alternative to the currently used presumptive tests. We have developed a customized workflow for interpretation of bacterial 16S sequence data based on a model composed of Partial Least Squares (PLS) in combination with Linear Discriminant Analysis (LDA). Large data sets from the Human Microbiome Project (HMP) and the American Gut Project (AGP) were used to test different settings in order to optimize performance. From the initial cross-validation of body fluid recognition within the HMP data, the optimal overall accuracy was close to 98%. Sensitivity values for the fecal and oral samples were ≥0.99, followed by the vaginal samples with 0.98 and the skin and nasal samples with 0.96 and 0.81 respectively. Specificity values were high for all 5 categories, mostly >0.99. This optimal performance was achieved by using the following settings: Taxonomic profiles based on operational taxonomic units (OTUs) with 0.98 identity (OTU98), Aitchisons simplex transform with C = 1 pseudo-count and no regularization (r = 1) in the PLS step. Variable selection did not improve the performance further. To test for robustness across sequencing platforms, we also trained the classifier on HMP data and tested on the AGP data set. In this case, the standard OTU based approach showed moderately decline in accuracy. However, by using taxonomic profiles made by direct assignment of reads to a genus, we were able to nearly maintain the high accuracy levels. The optimal combination of settings was still used, except the taxonomic level being genus instead of OTU98. The performance may be improved even further by using higher resolution taxonomic bins.}, }
@article {pmid30069974, year = {2018}, author = {Mert, I and Walther-Antonio, M and Mariani, A}, title = {Case for a role of the microbiome in gynecologic cancers: Clinician's perspective.}, journal = {The journal of obstetrics and gynaecology research}, volume = {44}, number = {9}, pages = {1693-1704}, doi = {10.1111/jog.13701}, pmid = {30069974}, issn = {1447-0756}, mesh = {Dysbiosis/*complications ; Endometrial Neoplasms/*etiology ; Female ; Humans ; *Microbiota ; Ovarian Neoplasms/*etiology ; }, abstract = {In this review, we aimed to provide insight into the microbiome and its association with endometrial and ovarian cancer and their risk factors. We reviewed the literature focusing on the relationship between the microbiome and cancer, as well as the relationship between gynecologic diseases and cancers. The human body contains different kinds of microorganisms in various body parts, which is termed the microbiome. The number of microorganisms that live in and on the human body is greater than that of the human germ and somatic cells by 10-fold. The relationship between a human and their microbiome is complex; it is also one of the most important components of homeostasis. Impairment of microbiome-host homeostasis has been associated with obesity, several cancers, preterm labor, inflammatory and allergic conditions and neurodevelopmental disorders. Direct and strong causal relationships have been established for several cancers and microorganisms, such as gastric lymphoma and Helicobacter pylori infection. Interestingly, eradication of the infectious agents has also been shown to be therapeutic. The association between cancer and the microbiome, however, is more complicated than a 1 bacteria-1 cancer model, and a shift in a healthy microbiome can result in various cancers via inflammation, change in microenvironment or DNA-damaging toxins. The human microbiome is an integral part of homeostasis. Understanding the mechanisms that cause dysbiosis will enable us to elucidate the pathways that result in malignancy and investigate new treatment modalities.}, }
@article {pmid30066739, year = {2018}, author = {Costa, AN and Costa, FMD and Campos, SV and Salles, RK and Athanazio, RA}, title = {The pulmonary microbiome: challenges of a new paradigm.}, journal = {Jornal brasileiro de pneumologia : publicacao oficial da Sociedade Brasileira de Pneumologia e Tisilogia}, volume = {44}, number = {5}, pages = {424-432}, pmid = {30066739}, issn = {1806-3756}, mesh = {Dysbiosis/*immunology ; Humans ; Immune System/*microbiology ; Lung/*microbiology ; Lung Diseases/*microbiology ; Microbiota/*physiology ; }, abstract = {The study of the human microbiome-and, more recently, that of the respiratory system-by means of sophisticated molecular biology techniques, has revealed the immense diversity of microbial colonization in humans, in human health, and in various diseases. Apparently, contrary to what has been believed, there can be nonpathogenic colonization of the lungs by microorganisms such as bacteria, fungi, and viruses. Although this physiological lung microbiome presents low colony density, it presents high diversity. However, some pathological conditions lead to a loss of that diversity, with increasing concentrations of some bacterial genera, to the detriment of others. Although we possess qualitative knowledge of the bacteria present in the lungs in different states of health or disease, that knowledge has advanced to an understanding of the interaction of this microbiota with the local and systemic immune systems, through which it modulates the immune response. Given this intrinsic relationship between the microbiota and the lungs, studies have put forth new concepts about the pathophysiological mechanisms of homeostasis in the respiratory system and the potential dysbiosis in some diseases, such as cystic fibrosis, COPD, asthma, and interstitial lung disease. This departure from the paradigm regarding knowledge of the lung microbiota has made it imperative to improve understanding of the role of the microbiome, in order to identify possible therapeutic targets and to develop innovative clinical approaches. Through this new leap of knowledge, the results of preliminary studies could translate to benefits for our patients.}, }
@article {pmid30058389, year = {2018}, author = {Greco, V and Piras, C and Pieroni, L and Ronci, M and Putignani, L and Roncada, P and Urbani, A}, title = {Applications of MALDI-TOF mass spectrometry in clinical proteomics.}, journal = {Expert review of proteomics}, volume = {15}, number = {8}, pages = {683-696}, doi = {10.1080/14789450.2018.1505510}, pmid = {30058389}, issn = {1744-8387}, mesh = {Body Fluids/metabolism ; Drug Discovery ; Humans ; Neoplasm, Residual/metabolism ; *Proteomics ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization/*methods ; }, abstract = {The development of precision medicine requires advanced technologies to address the multifactorial disease stratification and to support personalized treatments. Among omics techniques, proteomics based on Mass Spectrometry (MS) is becoming increasingly relevant in clinical practice allowing a phenotypic characterization of the dynamic functional status of the organism. From this perspective, Matrix Assisted Laser Desorption Ionization Time of Flight (MALDI-TOF) MS is a suitable platform for providing a high-throughput support to clinics. Areas covered: This review aims to provide an updated overview of MALDI-TOF MS applications in clinical proteomics. The most relevant features of this analysis have been discussed, highlighting both pre-analytical and analytical factors that are crucial in proteomics studies. Particular emphasis is placed on biofluids proteomics for biomarkers discovery and on recent progresses in clinical microbiology, drug monitoring, and minimal residual disease (MRD). Expert commentary: Despite some analytical limitations, the latest technological advances together with the easiness of use, the low time and low cost consuming and the high throughput are making MALDI-TOF MS instruments very attractive for the clinical practice. These features offer a significant potential for the routine of the clinical laboratory and ultimately for personalized medicine.}, }
@article {pmid30056862, year = {2018}, author = {Rosa, CP and Brancaglion, GA and Miyauchi-Tavares, TM and Corsetti, PP and de Almeida, LA}, title = {Antibiotic-induced dysbiosis effects on the murine gastrointestinal tract and their systemic repercussions.}, journal = {Life sciences}, volume = {207}, number = {}, pages = {480-491}, doi = {10.1016/j.lfs.2018.06.030}, pmid = {30056862}, issn = {1879-0631}, mesh = {Animals ; Anti-Bacterial Agents/*adverse effects ; Cytokines/metabolism ; Disease Models, Animal ; Dysbiosis/*drug therapy ; Fatty Acids, Volatile/chemistry ; Gastrointestinal Microbiome/*drug effects ; Gastrointestinal Tract/*drug effects/microbiology ; Homeostasis ; Humans ; Inflammation ; Mice ; T-Lymphocyte Subsets ; T-Lymphocytes/cytology ; }, abstract = {The gastrointestinal tract has become a focus of study recently. The crosstalk between microbiota, especially bacteria, and the intestinal mucosa has to be accurately balanced in order to maintain physiological homeostasis in the human body. This dynamic interaction results in different levels of short-chain fatty acids (SCFAs), IgA, and T cell lymphocyte subsets, which could lead the human body towards health or disease. The disruption of this microbiome characterises gut dysbiosis. Antibiotics are usually prescribed to fight against bacterial infection. They can also modulate the human microbiome, since it acts directly over organisational taxonomic units (OTUs) when taken orally. As a result, these pharmaceuticals enable gut dysbiosis and its systemic effects due to microbiome disturbance. Here, current data have been gathered from mice model experiments and epidemiological studies in an antibiotic-centred perspective. The presented data suggest the importance of translational studies in a murine model focusing on GIT homeostasis with bacterial groups since any changes to the GIT-microbiota have systemic repercussions in human health and disease.}, }
@article {pmid30052903, year = {2018}, author = {Frey, AM and Ansbro, K and Kamble, NS and Pham, TK and Stafford, GP}, title = {Characterisation and pure culture of putative health-associated oral bacterium BU063 (Tannerella sp. HOT-286) reveals presence of a potentially novel glycosylated S-layer.}, journal = {FEMS microbiology letters}, volume = {365}, number = {17}, pages = {}, doi = {10.1093/femsle/fny180}, pmid = {30052903}, issn = {1574-6968}, support = {BB/K501098/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Amino Acid Sequence ; Humans ; Membrane Glycoproteins/chemistry/genetics/*metabolism ; Mouth/*microbiology ; Muramic Acids/metabolism ; Propionibacterium acnes/growth &amp; development/metabolism ; Sequence Alignment ; Tannerella forsythia/genetics/growth &amp; development/isolation &amp; purification/*metabolism ; }, abstract = {Tannerella HOT-286 (phylotype BU063) is a recently identified novel filamentous Gram-negative anaerobic oral bacterium cultured for the first time recently in co-culture with Propionibacterium acnes. In contrast to the related periodontal disease-associated pathobiont Tannerella forsythia, it is considered a putative health-associated bacterium. In this paper, we identified that this organism could be grown in pure culture if N-acetyl muramic acid (NAM) was provided in the media, although surprisingly the genetic basis of this phenomenon is not likely to be due to a lack of NAM synthesis genes. During further microbiological investigations, we showed for the first time that T. HOT-286 possesses a prominent extracellular S-layer with a novel morphology putatively made up of two proteins modified with an unknown glycan. These data further our knowledge of this poorly understood organism and genus that is an important part of the oral and human microbiome.}, }
@article {pmid30052094, year = {2018}, author = {Laing, B and Barnett, MPG and Marlow, G and Nasef, NA and Ferguson, LR}, title = {An update on the role of gut microbiota in chronic inflammatory diseases, and potential therapeutic targets.}, journal = {Expert review of gastroenterology &amp; hepatology}, volume = {12}, number = {10}, pages = {969-983}, doi = {10.1080/17474124.2018.1505497}, pmid = {30052094}, issn = {1747-4132}, mesh = {Age Factors ; Diet ; Dysbiosis/*complications/*therapy ; Environment ; Exercise ; Fatty Acids, Volatile/metabolism ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/genetics/immunology/*physiology ; Humans ; Inflammation/*microbiology ; Intestinal Mucosa/immunology/*physiology ; Probiotics/therapeutic use ; }, abstract = {The human microbiome plays a critical role in human health, having metabolic, protective, and trophic functions, depending upon its' exact composition. This composition is affected by a number of factors, including the genetic background of the individual, early life factors (including method of birth, length of breastfeeding) and nature of the diet and other environmental exposures (including cigarette smoking) and general life habits. It plays a key role in the control of inflammation, and in turn, its' composition is significantly influenced by inflammation. Areas covered: We consider metabolic, protective, and trophic functions of the microbiome and influences through the lifespan from post-partum effects, to diet later in life in healthy older adults, the effects of aging on both its' composition, and influence on health and potential therapeutic targets that may have anti-inflammatory effects. Expert commentary: The future will see the growth of more effective therapies targeting the microbiome particularly with respect to the use of specific nutrients and diets personalized to the individual.}, }
@article {pmid30042747, year = {2018}, author = {Westerik, N and Kort, R and Sybesma, W and Reid, G}, title = {Lactobacillus rhamnosus Probiotic Food as a Tool for Empowerment Across the Value Chain in Africa.}, journal = {Frontiers in microbiology}, volume = {9}, number = {}, pages = {1501}, pmid = {30042747}, issn = {1664-302X}, abstract = {Perhaps by serendipity, but Lactobacillus rhamnosus has emerged from the 1980s as the most researched probiotic species. The many attributes of the two main probiotic strains of the species, L. rhamnosus GG and GR-1, have made them suitable for applications to developing countries in Africa and beyond. Their use with a Streptococcus thermophilus starter strain C106, in the fermentation of milk, millet, and juices has provided a means to reach over 250,000 consumers of the first probiotic food on the continent. The social and economical implications for this translational research are significant, and especially pertinent for people living in poverty, with malnutrition and exposure to environmental toxins and infectious diseases including HIV and malaria. This example of probiotic applications illustrates the power of microbes in positively impacting the lives of women, men, and children, right across the food value chain.}, }
@article {pmid30039798, year = {2018}, author = {Zhang, XS and Li, J and Krautkramer, KA and Badri, M and Battaglia, T and Borbet, TC and Koh, H and Ng, S and Sibley, RA and Li, Y and Pathmasiri, W and Jindal, S and Shields-Cutler, RR and Hillmann, B and Al-Ghalith, GA and Ruiz, VE and Livanos, A and van 't Wout, AB and Nagalingam, N and Rogers, AB and Sumner, SJ and Knights, D and Denu, JM and Li, H and Ruggles, KV and Bonneau, R and Williamson, RA and Rauch, M and Blaser, MJ}, title = {Antibiotic-induced acceleration of type 1 diabetes alters maturation of innate intestinal immunity.}, journal = {eLife}, volume = {7}, number = {}, pages = {}, pmid = {30039798}, issn = {2050-084X}, support = {T35 DK007421/DK/NIDDK NIH HHS/United States ; R01 DK110014/DK/NIDDK NIH HHS/United States ; R01DK110014/NH/NIH HHS/United States ; T32 GM008692/GM/NIGMS NIH HHS/United States ; T32 GM007308/GM/NIGMS NIH HHS/United States ; 5T35DK007421/NH/NIH HHS/United States ; F30 DK108494/DK/NIDDK NIH HHS/United States ; R37GM059785/NH/NIH HHS/United States ; 15-A0-00-00-0039-29-01//Janssen Research and Development/International ; -33.17CVD01//Fondation Leducq/International ; T32 DK007665/DK/NIDDK NIH HHS/United States ; R37 GM059785/GM/NIGMS NIH HHS/United States ; F30DK108494/NH/NIH HHS/United States ; 15-A0-00-00-0039-29-01//Janssen Labs London/International ; }, mesh = {Adaptive Immunity/drug effects ; Animals ; Anti-Bacterial Agents/*adverse effects/immunology ; Diabetes Mellitus, Type 1/*immunology/microbiology/pathology ; Female ; Gastrointestinal Microbiome/drug effects/*immunology ; Ileum/immunology/microbiology ; Immunity, Innate/*drug effects/immunology ; Intestines/microbiology ; Mice ; Mice, Inbred NOD ; Microbiota/drug effects/immunology ; }, abstract = {The early-life intestinal microbiota plays a key role in shaping host immune system development. We found that a single early-life antibiotic course (1PAT) accelerated type 1 diabetes (T1D) development in male NOD mice. The single course had deep and persistent effects on the intestinal microbiome, leading to altered cecal, hepatic, and serum metabolites. The exposure elicited sex-specific effects on chromatin states in the ileum and liver and perturbed ileal gene expression, altering normal maturational patterns. The global signature changes included specific genes controlling both innate and adaptive immunity. Microbiome analysis revealed four taxa each that potentially protect against or accelerate T1D onset, that were linked in a network model to specific differences in ileal gene expression. This simplified animal model reveals multiple potential pathways to understand pathogenesis by which early-life gut microbiome perturbations alter a global suite of intestinal responses, contributing to the accelerated and enhanced T1D development.}, }
@article {pmid30021103, year = {2018}, author = {Proal, AD and Marshall, TG}, title = {Re-framing the theory of autoimmunity in the era of the microbiome: persistent pathogens, autoantibodies, and molecular mimicry.}, journal = {Discovery medicine}, volume = {25}, number = {140}, pages = {299-308}, pmid = {30021103}, issn = {1944-7930}, mesh = {Autoantibodies/*immunology ; *Autoimmunity ; Dysbiosis/immunology/microbiology ; Humans ; *Microbiota ; *Models, Immunological ; Molecular Mimicry/*immunology ; }, abstract = {The theory of autoimmunity was developed at a time when the human body was regarded as largely sterile. Antibodies in patients with chronic inflammatory disease could consequently not be tied to persistent human pathogens. The concept of the "autoantibody" was created to reconcile this phenomenon. Today, however, the discovery of the human microbiome has revolutionized our understanding of human biology. Humans are superorganisms that harbor trillions of persistent microbial cells. Indeed, vast human microbiomes have been detected in human tissue and blood. These microbial ecosystems harbor thousands of newly identified bacteria, viruses, and other microorganisms -- most of which can act as pathogens under conditions of immunosuppression. The theory of autoimmunity must be revised to account for the human microbiome. Here, we propose a model in which "autoantibodies" are created in response to chronic, persistent microbiome pathogens. The structural homology (molecular mimicry) between pathogen and host proteins can result in "collateral damage" to surrounding human tissue. This calls for a paradigm shift in autoimmune disease treatment. Immunosuppressive medications palliate inflammatory symptoms at the expense of microbiome health and balance. In contrast, treatments that support the immune system in autoimmune disease could allow patients to target pathogens at the root of the disease process.}, }
@article {pmid30019906, year = {2018}, author = {Wang, AY and Thuy-Boun, PS and Stupp, GS and Su, AI and Wolan, DW}, title = {Triflic Acid Treatment Enables LC-MS/MS Analysis of Insoluble Bacterial Biomass.}, journal = {Journal of proteome research}, volume = {17}, number = {9}, pages = {2978-2986}, pmid = {30019906}, issn = {1535-3907}, support = {U54 GM114833/GM/NIGMS NIH HHS/United States ; }, mesh = {Bacillus subtilis/*chemistry/genetics/metabolism ; Bacterial Proteins/*isolation &amp; purification ; Chromatography, Liquid ; Complex Mixtures/chemistry ; Gastrointestinal Microbiome/genetics ; Humans ; Jurkat Cells ; Membrane Proteins/*isolation &amp; purification ; Mesylates/*chemistry ; Metagenome ; Proteomics/*methods ; Pseudomonas aeruginosa/*chemistry/genetics/metabolism ; Sonication/methods ; Tandem Mass Spectrometry ; }, abstract = {The lysis and extraction of soluble bacterial proteins from cells is a common practice for proteomics analyses, but insoluble bacterial biomasses are often left behind. Here, we show that with triflic acid treatment, the insoluble bacterial biomass of Gram[-] and Gram[+] bacteria can be rendered soluble. We use LC-MS/MS shotgun proteomics to show that bacterial proteins in the soluble and insoluble postlysis fractions differ significantly. Additionally, in the case of Gram[-] Pseudomonas aeruginosa, triflic acid treatment enables the enrichment of cell-envelope-associated proteins. Finally, we apply triflic acid to a human microbiome sample to show that this treatment is robust and enables the identification of a new, complementary subset of proteins from a complex microbial mixture.}, }
@article {pmid30017599, year = {2018}, author = {Chanyi, RM and Alzubaidi, R and Leung, EJY and Wilcox, HB and Brock, GB and Burton, JP}, title = {Inflatable Penile Prostheses Implantation: Does Antibiotic Exposure Matter?.}, journal = {Sexual medicine}, volume = {6}, number = {3}, pages = {248-254}, pmid = {30017599}, issn = {2050-1161}, abstract = {BACKGROUND: Inflatable penile prosthetic (IPP) infections are unusual but carry high patient morbidity and healthcare costs.<br><br>AIM: To increase the bactericidal effect of IPP tubing material to prevent future bacterial infections and to determine whether this effect is time-dependent.<br><br>METHODS: A modified disk diffusion assay was developed to measure the zones of inhibition against Escherichia coli, Proteus mirabilis, Staphylococcus aureus, and Staphylococcus epidermidis when tubing was immersed in gentamycin, ampicillin, tetracycline, kanamycin, erythromycin, or ciprofloxacin. To further assess the efficacy of this approach, IPP tubing was exposed to ampicillin or ciprofloxacin for 30 seconds, 2 minutes, 10 minutes, or 60 minutes.<br><br>OUTCOMES: Bacterial zones of inhibition against IPP tubing material exposed to various treatments.<br><br>RESULTS: IPP tubing was more effective against Gram-positive bacteria (S&#xa0;aureus and S&#xa0;epidermidis) then Gram-negative bacteria (E&#xa0;coli and P&#xa0;mirabilis). Immersing IPP tubing material in ampicillin or ciprofloxacin increased bactericidal effect of tubing material against Gram-positive and Gram-negative bacteria, respectively. The observed inhibitory effect was time dependent.<br><br>CLINICAL TRANSLATION: Exposing IPP to a specific antimicrobial directly before implantation increases the bactericidal properties of the material, potentially decreasing the likelihood of infection.<br><br>STRENGTHS &amp; LIMITATIONS: This study is limited in that it is in&#xa0;vitro experimentation observing the effect of a single strain of each bacterium. Although the strains used were clinically relevant, further analysis is required to determine whether these results were strain specific.<br><br>CONCLUSION: Immersing IPP material into an antibiotic solution, such as ampicillin or ciprofloxacin, increases the bactericidal properties and may aid in the prevention of infection. Chanyi RM, Alzubaidi R, Leung EJY, Wilcox HB, Brock GB, Burton JP. Inflatable Penile Prostheses Implantation: Does Antibiotic Exposure Matter? Sex Med 2018;6;248-254.}, }
@article {pmid30015225, year = {2018}, author = {Schnorr, SL}, title = {Meanings, measurements, and musings on the significance of patterns in human microbiome variation.}, journal = {Current opinion in genetics &amp; development}, volume = {53}, number = {}, pages = {43-52}, doi = {10.1016/j.gde.2018.06.014}, pmid = {30015225}, issn = {1879-0380}, mesh = {Bacteria/classification/*genetics ; Gastrointestinal Microbiome/*genetics ; Humans ; *Metagenomics ; Microbiota/*genetics ; Transcriptome/genetics ; }, abstract = {Variation of the human microbiome is a multidimensional value depending on the question of interest. Unlike traditional human genetics, which most often deals with variation at the level of genes or genetic sequences, microbiome variation may be most relevant at the functional level and can be interrogated a number of ways. Most common methods are marker gene metataxonomic surveys or shotgun metagenomic sequencing, however more direct indicators of microbial activity that are gaining popularity include metabolomic and metatranscriptomic surveys. With all these data and promise in human microbiome research, it requires that we reassess what is meant by variation of the human microbiome and how its significance impacts the ability of microbiome research to be informative on a range of topics from evolutionary theory to clinical outcomes. Learning from mistakes is essential to advancing the field, and new sophisticated analysis tools are helping to crystallize associations between microbiome variation and its drivers so that firm ground supports future explorations of mechanism. However, the body of current data suggests that these may be highly individualized due to the array of interactions between the host, the microbiome, and the environment. As a result, microbiome researchers need to be cognizant of population contexts and the limits these impose on conclusive outcomes.}, }
@article {pmid30014852, year = {2018}, author = {Yao, L and Seaton, SC and Ndousse-Fetter, S and Adhikari, AA and DiBenedetto, N and Mina, AI and Banks, AS and Bry, L and Devlin, AS}, title = {A selective gut bacterial bile salt hydrolase alters host metabolism.}, journal = {eLife}, volume = {7}, number = {}, pages = {}, pmid = {30014852}, issn = {2050-084X}, support = {P30DK034854/NH/NIH HHS/United States ; U2C DK059637/DK/NIDDK NIH HHS/United States ; P30 DK034854/DK/NIDDK NIH HHS/United States ; P30 DK020593/DK/NIDDK NIH HHS/United States ; P30 CA006516/CA/NCI NIH HHS/United States ; U24 DK059637/DK/NIDDK NIH HHS/United States ; }, mesh = {Amidohydrolases/genetics/*metabolism ; Animals ; Bacteroides thetaiotaomicron/*enzymology/genetics/isolation &amp; purification ; Body Weight ; Circadian Rhythm ; Gastrointestinal Tract/*microbiology ; Gene Expression Profiling ; Germ-Free Life ; *Host Microbial Interactions ; Immunity ; Intestines/physiology ; Liver/physiology ; Metabolism ; Mice ; Respiration ; Taurocholic Acid/*analogs &amp; derivatives/metabolism ; }, abstract = {The human gut microbiota impacts host metabolism and has been implicated in the pathophysiology of obesity and metabolic syndromes. However, defining the roles of specific microbial activities and metabolites on host phenotypes has proven challenging due to the complexity of the microbiome-host ecosystem. Here, we identify strains from the abundant gut bacterial phylum Bacteroidetes that display selective bile salt hydrolase (BSH) activity. Using isogenic strains of wild-type and BSH-deleted Bacteroides thetaiotaomicron, we selectively modulated the levels of the bile acid tauro-β-muricholic acid in monocolonized gnotobiotic mice. B. thetaiotaomicron BSH mutant-colonized mice displayed altered metabolism, including reduced weight gain and respiratory exchange ratios, as well as transcriptional changes in metabolic, circadian rhythm, and immune pathways in the gut and liver. Our results demonstrate that metabolites generated by a single microbial gene and enzymatic activity can profoundly alter host metabolism and gene expression at local and organism-level scales.}, }
@article {pmid30014616, year = {2018}, author = {Rands, CM and Starikova, EV and Brüssow, H and Kriventseva, EV and Govorun, VM and Zdobnov, EM}, title = {ACI-1 beta-lactamase is widespread across human gut microbiomes in Negativicutes due to transposons harboured by tailed prophages.}, journal = {Environmental microbiology}, volume = {20}, number = {6}, pages = {2288-2300}, doi = {10.1111/1462-2920.14276}, pmid = {30014616}, issn = {1462-2920}, support = {IZLRZ3_163863 16-54-21012//Schweizerischer Nationalfonds zur F&#xf6;rderung der Wissenschaftlichen Forschung/International ; //Russian Foundation for Basic Research/International ; }, mesh = {Anti-Bacterial Agents/pharmacology ; Bacteria/classification/drug effects/genetics/*metabolism ; China ; Drug Resistance, Bacterial/*genetics ; Europe ; Firmicutes/genetics ; *Gastrointestinal Microbiome ; Gene Transfer, Horizontal ; Humans ; Metagenome ; Phylogeny ; Prophages/*genetics ; United States ; beta-Lactamases/genetics/*metabolism ; }, abstract = {Antibiotic resistance is increasing among pathogens, and the human microbiome contains a reservoir of antibiotic resistance genes. Acidaminococcus intestini is the first Negativicute bacterium (Gram-negative Firmicute) shown to be resistant to beta-lactam antibiotics. Resistance is conferred by the aci1 gene, but its evolutionary history and prevalence remain obscure. We discovered that ACI-1 proteins are phylogenetically distinct from beta-lactamases of Gram-positive Firmicutes and that aci1 occurs in bacteria scattered across the Negativicute clade, suggesting lateral gene transfer. In the reference A. intestini RyC-MR95 genome, we found transposons residing within a tailed prophage context are likely vehicles for aci1's mobility. We found aci1 in 56 (4.4%) of 1,267 human gut metagenomes, mostly hosted within A. intestini, and, where could be determined, mostly within a consistent mobile element constellation. These samples are from Europe, China and the USA, showing that aci1 is distributed globally. We found that for most Negativicute assemblies with aci1, the prophage observed in A. instestini is absent, but in all cases aci1 is flanked by varying transposons. The chimeric mobile elements we identify here likely have a complex evolutionary history and potentially provide multiple complementary mechanisms for antibiotic resistance gene transfer both within and between cells.}, }
@article {pmid30010322, year = {2018}, author = {Stauber, RH and Siemer, S and Becker, S and Ding, GB and Strieth, S and Knauer, SK}, title = {Small Meets Smaller: Effects of Nanomaterials on Microbial Biology, Pathology, and Ecology.}, journal = {ACS nano}, volume = {12}, number = {7}, pages = {6351-6359}, doi = {10.1021/acsnano.8b03241}, pmid = {30010322}, issn = {1936-086X}, mesh = {Agriculture ; Bacteria/chemistry/cytology/*metabolism ; Biotechnology ; Fungi/chemistry/cytology/*metabolism ; Humans ; *Microbiota ; Nanomedicine ; *Nanostructures/chemistry/microbiology/ultrastructure ; *Nanotechnology ; }, abstract = {As functionalities and levels of complexity in nanomaterials have increased, unprecedented control over microbes has been enabled, as well. In addition to being pathogens and relevant to the human microbiome, microbes are key players for sustainable biotechnology. To overcome current constraints, mechanistic understanding of nanomaterials' physicochemical characteristics and parameters at the nano-bio interface affecting nanomaterial-microbe crosstalk is required. In this Perspective, we describe key nanomaterial parameters and biological outputs that enable controllable microbe-nanomaterial interactions while minimizing design complexity. We discuss the role of biomolecule coronas, including the problem of nanoantibiotic resistance, and speculate on the effects of nanomaterial-microbe complex formation on the outcomes and fates of microbial pathogens. We close by summarizing our current knowledge and noting areas that require further exploration to overcome current limitations for next-generation practical applications of nanotechnology in medicine and agriculture.}, }
@article {pmid30009382, year = {2018}, author = {Ceccarelli, F and Orrù, G and Pilloni, A and Bartosiewicz, I and Perricone, C and Martino, E and Lucchetti, R and Fais, S and Vomero, M and Olivieri, M and di Franco, M and Priori, R and Riccieri, V and Scrivo, R and Shoenfeld, Y and Alessandri, C and Conti, F and Polimeni, A and Valesini, G}, title = {Porphyromonas gingivalis in the tongue biofilm is associated with clinical outcome in rheumatoid arthritis patients.}, journal = {Clinical and experimental immunology}, volume = {194}, number = {2}, pages = {244-252}, pmid = {30009382}, issn = {1365-2249}, mesh = {Adult ; Aged ; Arthritis, Rheumatoid/epidemiology/*immunology ; Bacteroidaceae Infections/epidemiology/*immunology ; Biofilms ; Case-Control Studies ; Cohort Studies ; Disease Progression ; Female ; Humans ; Italy/epidemiology ; Male ; Microbiota/*immunology ; Middle Aged ; Periodontitis/*immunology ; Porphyromonas gingivalis/*physiology ; Prevalence ; Tongue/microbiology/*pathology ; }, abstract = {Several studies have suggested a link between human microbiome and rheumatoid arthritis (RA) development. Porphyromonas gingivalis seems involved in RA initiation and progression, as supported by the high occurrence of periodontitis. In this case-control study, we analysed tongue P. gingivalis presence and quantification in a large healthy and RA cohort. We enrolled 143 RA patients [male/female (M/F) 32/111, mean ± standard deviation (s.d.), age 57·5 ± 19·8 years, mean ± s.d. disease duration 155·9 ± 114·7 months); 36 periodontitis patients (M/F 11/25, mean ± s.d., age 56 ± 9·9 years, mean ± s.d. disease duration 25·5 ± 20·9 months); and 57 patients (M/F 12/45, mean ± s.d., age 61·4 ± 10·9 years, mean ± s.d. disease duration 62·3 ± 66·9 months) with knee osteoarthritis or fibromyalgia. All subjects underwent a standard cytological swab to identify the rate of P. gingivalis/total bacteria by using quantitative real-time polymerase chain reaction. The prevalence of P. gingivalis resulted similarly in RA and periodontitis patients (48·9 versus 52·7%, P = not significant). Moreover, the prevalence of this pathogen was significantly higher in RA and periodontitis patients in comparison with control subjects (P = 0·01 and P = 0·003, respectively). We found a significant correlation between P. gingivalis rate in total bacteria genomes and disease activity score in 28 joints (DAS28) (erythrocyte sedimentation rate) (r = 0·4, P = 0·01). RA patients in remission showed a significantly lower prevalence of P. gingivalis in comparison with non-remission (P = 0·02). We demonstrated a significant association between the percentage of P. gingivalis on the total tongue biofilm and RA disease activity (DAS28), suggesting that the oral cavity microbiological status could play a role in the pathogenic mechanisms of inflammation, leading to more active disease.}, }
@article {pmid30007202, year = {2018}, author = {Stegen, JC and Bottos, EM and Jansson, JK}, title = {A unified conceptual framework for prediction and control of microbiomes.}, journal = {Current opinion in microbiology}, volume = {44}, number = {}, pages = {20-27}, doi = {10.1016/j.mib.2018.06.002}, pmid = {30007202}, issn = {1879-0364}, mesh = {Bacteria/classification/genetics/*growth &amp; development/isolation &amp; purification ; Ecosystem ; Humans ; *Microbiota ; }, abstract = {Microbiomes impact nearly all systems on Earth, and despite vast differences among systems, we contend that it is possible and highly beneficial to develop a unified conceptual framework for understanding microbiome dynamics that is applicable across systems. The ability to robustly predict and control environmental and human microbiomes would provide impactful opportunities to sustain and improve the health of ecosystems and humans alike. Doing so requires understanding the processes governing microbiome temporal dynamics, which currently presents an enormous challenge. We contend, however, that new opportunities can emerge by placing studies of both environmental and human microbiome temporal dynamics in the context of a unified conceptual framework. Our conceptual framework poses that factors influencing the temporal dynamics of microbiomes can be grouped into three broad categories: biotic and abiotic history, internal dynamics, and external forcing factors. Both environmental and human microbiome science study these factors, but not in a coordinated or consistent way. Here we discuss opportunities for greater crosstalk across these domains, such as leveraging specific ecological concepts from environmental microbiome science to guide optimization of strategies to manipulate human microbiomes towards improved health. To achieve unified understanding, it is necessary to have a common body of theory developed from explicit iteration between models and molecular-based characterization of microbiome dynamics across systems. Only through such model-experiment iteration will we eventually achieve prediction and control across microbiomes that impact ecosystem sustainability and human health.}, }
@article {pmid30003599, year = {2019}, author = {Lorimer, J}, title = {Hookworms Make Us Human: The Microbiome, Eco-immunology, and a Probiotic Turn in Western Health Care.}, journal = {Medical anthropology quarterly}, volume = {33}, number = {1}, pages = {60-79}, doi = {10.1111/maq.12466}, pmid = {30003599}, issn = {0745-5194}, mesh = {Ancylostomatoidea ; Animals ; Anthropology, Medical ; *Ecology ; *Hookworm Infections ; Humans ; Infectious Disease Medicine ; *Microbiota ; Probiotics/*therapeutic use ; }, abstract = {Historians of science have identified an ecological turn underway in immunology, driven by the mapping of the human microbiome and wider environmentalist anxieties. A figure is emerging of the human as a holobiont, composed of microbes and threatened by both microbial excess and microbial absence. Antimicrobial approaches to germ warfare are being supplemented by probiotic approaches to restoring microbial life. This article examines the political ecology of this probiotic turn in Western health care. It focuses on Necator americanus-a species of human hookworm-and its relations with immunologists. The analysis moves from a history of human disentanglement from hookworm, to contemporary anxieties about their absence. It examines the reintroduction of worms for helminthic therapy and explores emerging trajectories for probiotic health care involving the synthesis, modification, and/or restoration of worms and their salutary ecologies. The conclusion differentiates these trajectories and identifies an emerging model of "post-paleo" microbiopolitics.}, }
@article {pmid30001289, year = {2018}, author = {Archibugi, L and Signoretti, M and Capurso, G}, title = {The Microbiome and Pancreatic Cancer: An Evidence-based Association?.}, journal = {Journal of clinical gastroenterology}, volume = {52 Suppl 1, Proceedings from the 9th Probiotics, Prebiotics and New Foods, Nutraceuticals and Botanicals for Nutrition &amp; Human and Microbiota Health Meeting, held in Rome, Italy from September 10 to 12, 2017}, number = {}, pages = {S82-S85}, doi = {10.1097/MCG.0000000000001092}, pmid = {30001289}, issn = {1539-2031}, mesh = {Animals ; Evidence-Based Medicine ; Helicobacter Infections/microbiology ; Helicobacter pylori ; Humans ; Immune System/*microbiology ; Intestines/immunology/microbiology ; Microbiota/*immunology ; Pancreas/immunology/*microbiology ; Pancreatic Neoplasms/immunology/*microbiology ; Risk Factors ; }, abstract = {Many risk factors for pancreatic cancer are related with microbiome alteration. In the past few years, the human microbiome and its relation with the immune system have been linked with carcinogenesis of different organs distant from the gut, including the pancreas. Patterns of oral microbiome associated with periodontitis are associated with an increased risk of pancreatic cancer, possibly because of the increased systemic inflammatory response, or to the capacity of some specific bacteria to alter the host immune response, making it more favorable to cancer cells. Helicobacter pylori infection when affecting the gastric body mucosa with subsequent hypochlorhydria also seems associated with an increased risk of pancreatic cancer. The composition of the intestinal microbiome is different in animal models and in humans with pancreatic cancer who have a distinct microbiome population compared with controls. Some specific bacteria can migrate from the intestine to the pancreas, and their ablation restores the immune system activity through its reprogramming with a switch toward a Th1 response and displays a protective effect toward tumor growth. More research in this area might lead to progress in terms of pancreatic cancer prevention and treatment, possibly in association with immunotherapy.}, }
@article {pmid29997602, year = {2018}, author = {Xiao, J and Chen, L and Johnson, S and Yu, Y and Zhang, X and Chen, J}, title = {Predictive Modeling of Microbiome Data Using a Phylogeny-Regularized Generalized Linear Mixed Model.}, journal = {Frontiers in microbiology}, volume = {9}, number = {}, pages = {1391}, pmid = {29997602}, issn = {1664-302X}, support = {U01 FD005875/FD/FDA HHS/United States ; }, abstract = {Recent human microbiome studies have revealed an essential role of the human microbiome in health and disease, opening up the possibility of building microbiome-based predictive models for individualized medicine. One unique characteristic of microbiome data is the existence of a phylogenetic tree that relates all the microbial species. It has frequently been observed that a cluster or clusters of bacteria at varying phylogenetic depths are associated with some clinical or biological outcome due to shared biological function (clustered signal). Moreover, in many cases, we observe a community-level change, where a large number of functionally interdependent species are associated with the outcome (dense signal). We thus develop "glmmTree," a prediction method based on a generalized linear mixed model framework, for capturing clustered and dense microbiome signals. glmmTree uses the similarity between microbiomes, which is defined based on the microbiome composition and the phylogenetic tree, to predict the outcome. The effects of other predictive variables (e.g., age, sex) can be incorporated readily in the regression framework. Additional tuning parameters enable a data-adaptive approach to capture signals at different phylogenetic depth and abundance level. Simulation studies and real data applications demonstrated that "glmmTree" outperformed existing methods in the dense and clustered signal scenarios.}, }
@article {pmid29988721, year = {2018}, author = {Lourenςo, TGB and Spencer, SJ and Alm, EJ and Colombo, APV}, title = {Defining the gut microbiota in individuals with periodontal diseases: an exploratory study.}, journal = {Journal of oral microbiology}, volume = {10}, number = {1}, pages = {1487741}, pmid = {29988721}, issn = {2000-2297}, support = {P30 ES002109/ES/NIEHS NIH HHS/United States ; }, abstract = {Background: This exploratory study aimed to characterize the gut microbiome of individuals with different periodontal conditions, and correlate it with periodontal inflammation and tissue destruction. Methods: Stool samples were obtained from individuals presenting periodontal health (PH = 7), gingivitis (G = 14) and chronic periodontitis (CP = 23). The intestinal microbiome composition was determined by Illumina MiSeq sequencing. Results: A lower alpha-diversity in the gut microbiome of individuals with CP was observed, although no significant difference among groups was found (p > 0.01). Firmicutes, Proteobacteria, Verrucomicrobia and Euryarchaeota were increased, whereas Bacteroidetes were decreased in abundance in patients with periodontitis compared to PH. Prevotella (genus), Comamonadaceae (family) and Lactobacillales (order) were detected in higher numbers in G, while Bacteroidales (order) was predominant in PH (p < 0.01). Significant correlations (rho = 0.337-0.468, p < 0.01) were found between OTUs representative of periodontal pathogens and attachment loss. Mogibacteriaceae, Ruminococcaceae and Prevotella were able to discriminate individuals with periodontal diseases from PH (overall accuracy = 84%). Oral taxa were detected in high numbers in all stool samples. Conclusions: Individuals with periodontal diseases present a less diverse gut microbiome consistent with other systemic inflammatory diseases. High numbers of oral taxa related to periodontal destruction and inflammation were detected in the gut microbiome of individuals regardless of periodontal status.}, }
@article {pmid29984938, year = {2018}, author = {Li, BL and Cheng, L and Zhou, XD and Peng, X}, title = {[Research progress on the relationship between oral microbes and digestive system diseases].}, journal = {Hua xi kou qiang yi xue za zhi = Huaxi kouqiang yixue zazhi = West China journal of stomatology}, volume = {36}, number = {3}, pages = {331-335}, pmid = {29984938}, issn = {2618-0456}, mesh = {*Dental Caries/microbiology ; *Digestive System Diseases/microbiology ; Humans ; *Microbiota ; *Mouth Diseases/microbiology ; *Periodontal Diseases ; }, abstract = {The human microbiome project promoted further understanding on human oral microbes. Besides oral diseases such as dental caries, periodontal disease, and oral cancer, oral microbes are closely associated with systematic diseases. They have a close connection with digestive system diseases and even contribute to the origination and progression of colorectal cancer. By reviewing recent studies involving oral microbe-related digestive systemic diseases, we aim to propose the considerable role of oral microbes in relation to digestive systemic diseases and the way of oral microbes to multiple organs of digestive system.}, }
@article {pmid29983746, year = {2018}, author = {Tipton, L and Cuenco, KT and Huang, L and Greenblatt, RM and Kleerup, E and Sciurba, F and Duncan, SR and Donahoe, MP and Morris, A and Ghedin, E}, title = {Measuring associations between the microbiota and repeated measures of continuous clinical variables using a lasso-penalized generalized linear mixed model.}, journal = {BioData mining}, volume = {11}, number = {}, pages = {12}, pmid = {29983746}, issn = {1756-0381}, support = {UL1 RR024153/RR/NCRR NIH HHS/United States ; U01 AI031834/AI/NIAID NIH HHS/United States ; U01 AI035004/AI/NIAID NIH HHS/United States ; U01 AI037613/AI/NIAID NIH HHS/United States ; M01 RR000722/RR/NCRR NIH HHS/United States ; U01 AI035041/AI/NIAID NIH HHS/United States ; UM1 AI035043/AI/NIAID NIH HHS/United States ; U01 AI035043/AI/NIAID NIH HHS/United States ; U01 AI035040/AI/NIAID NIH HHS/United States ; U01 AI034993/AI/NIAID NIH HHS/United States ; K24 HL123342/HL/NHLBI NIH HHS/United States ; U01 AI035042/AI/NIAID NIH HHS/United States ; U01 AI037984/AI/NIAID NIH HHS/United States ; U01 HL098962/HL/NHLBI NIH HHS/United States ; U01 AI034989/AI/NIAID NIH HHS/United States ; UL1 TR000124/TR/NCATS NIH HHS/United States ; U01 AI034994/AI/NIAID NIH HHS/United States ; K24 HL087713/HL/NHLBI NIH HHS/United States ; UL1 TR000424/TR/NCATS NIH HHS/United States ; R01 HL090339/HL/NHLBI NIH HHS/United States ; UL1 TR001881/TR/NCATS NIH HHS/United States ; UL1 TR000004/TR/NCATS NIH HHS/United States ; U01 AI103408/AI/NIAID NIH HHS/United States ; U01 AI035039/AI/NIAID NIH HHS/United States ; U01 HD032632/HD/NICHD NIH HHS/United States ; U01 AI042590/AI/NIAID NIH HHS/United States ; }, abstract = {BACKGROUND: Human microbiome studies in clinical settings generally focus on distinguishing the microbiota in health from that in disease at a specific point in time. However, microbiome samples may be associated with disease severity or continuous clinical health indicators that are often assessed at multiple time points. While the temporal data from clinical and microbiome samples may be informative, analysis of this type of data can be problematic for standard statistical methods.<br><br>RESULTS: To identify associations between microbiota and continuous clinical variables measured repeatedly in two studies of the respiratory tract, we adapted a statistical method, the lasso-penalized generalized linear mixed model (LassoGLMM). LassoGLMM can screen for associated clinical variables, incorporate repeated measures of individuals, and address the large number of species found in the microbiome. As is common in microbiome studies, when the number of variables is an order of magnitude larger than the number of samples LassoGLMM can be imperfect in its variable selection. We overcome this limitation by adding a pre-screening step to reduce the number of variables evaluated in the model. We assessed the use of this adapted two-stage LassoGLMM for its ability to determine which microbes are associated with continuous repeated clinical measures.We found associations (retaining a non-zero coefficient in the LassoGLMM) between 10 laboratory measurements and 43 bacterial genera in the oral microbiota, and between 2 cytokines and 3 bacterial genera in the lung. We compared our associations with those identified by the Wilcoxon test after dichotomizing our outcomes and identified a non-significant trend towards differential abundance between high and low outcomes. Our two-step LassoGLMM explained more of the variance seen in the outcome of interest than other variants of the LassoGLMM method.<br><br>CONCLUSIONS: We demonstrated a method that can account for the large number of genera detected in microbiome studies and repeated measures of clinical or longitudinal studies, allowing for the detection of strong associations between microbes and clinical measures. By incorporating the design strengths of repeated measurements and a prescreening step to aid variable selection, our two-step LassoGLMM will be a useful analytic method for investigating relationships between microbes and repeatedly measured continuous outcomes.}, }
@article {pmid29976412, year = {2018}, author = {Kerry, RG and Patra, JK and Gouda, S and Park, Y and Shin, HS and Das, G}, title = {Benefaction of probiotics for human health: A review.}, journal = {Journal of food and drug analysis}, volume = {26}, number = {3}, pages = {927-939}, pmid = {29976412}, issn = {2224-6614}, mesh = {Animals ; Diabetes Mellitus/drug therapy ; Gastrointestinal Microbiome ; Health ; Humans ; Neoplasms/drug therapy ; Obesity/drug therapy ; Probiotics/*administration &amp; dosage ; }, abstract = {Humans are a unique reservoir of heterogeneous and vivacious group of microbes, which together forms the human-microbiome superorganism. Human gut serves as a home to over 100-1000 microbial species, which primarily modulate the host internal environment and thereby, play a major role in host health. This spectacular symbiotic relationship has attracted extensive research in this field. More specifically, these organisms play key roles in defense function, eupepsia along with catabolism and anabolism, and impact brain-gut responses. The emergence of microbiota with resistance and tolerance to existing conventional drugs and antibiotics has decreased the drug efficacies. Furthermore, the modern biotechnology mediated nano-encapsulated multiplex supplements appear to be high cost and inconvenient. Henceforth, a simple, low-cost, receptive and intrinsic approach to achieve health benefits is vital in the present era. Supplementation with probiotics, prebiotics, and synbiotics has shown promising results against various enteric pathogens due to their unique ability to compete with pathogenic microbiota for adhesion sites, to alienate pathogens or to stimulate, modulate and regulate the host's immune response by initiating the activation of specific genes in and outside the host intestinal tract. Probiotics have also been shown to regulate fat storage and stimulate intestinal angiogenesis. Hence, this study aims to underline the possible beneficial impact of probiotics for human health and medical sectors and for better lifestyle.}, }
@article {pmid29974051, year = {2018}, author = {Fankhauser, M and Moser, C and Nyfeler, T}, title = {Patents as Early Indicators of Technology and Investment Trends: Analyzing the Microbiome Space as a Case Study.}, journal = {Frontiers in bioengineering and biotechnology}, volume = {6}, number = {}, pages = {84}, pmid = {29974051}, issn = {2296-4185}, abstract = {The human microbiome is the collective of microbes living in symbiosis on and within humans. Modulating its composition and function has become an attractive means for the prevention and treatment of a variety of diseases including cancer. Since the initiation of the human microbiome project in 2007, the number of academic publications and active patent families around the microbiome has grown exponentially. Screening patent databases can be useful for the early detection and the tracking of new technology trends. However, it is not sufficient to assess portfolio sizes because emerging players with small but high-quality patent portfolios will be missed within the noise of large but low-quality portfolio owners. Here we used the consolidated database and software tool PatentSight to benchmark patent portfolios, and to analyze key patent owners and innovators in the microbiome space. Our study shows how in-depth patent analyses combining qualitative and quantitative parameters can identify actionable early indicators of technology and investment trends from large patent datasets.}, }
@article {pmid29973493, year = {2018}, author = {Castilla, IA and Woods, DF and Reen, FJ and O'Gara, F}, title = {Harnessing Marine Biocatalytic Reservoirs for Green Chemistry Applications through Metagenomic Technologies.}, journal = {Marine drugs}, volume = {16}, number = {7}, pages = {}, pmid = {29973493}, issn = {1660-3397}, mesh = {Animals ; Aquatic Organisms/*metabolism ; Biocatalysis ; Esterases/metabolism ; Humans ; Lipase/metabolism ; Metagenomics/methods ; }, abstract = {In a demanding commercial world, large-scale chemical processes have been widely utilised to satisfy consumer related needs. Chemical industries are key to promoting economic growth and meeting the requirements of a sustainable industrialised society. The market need for diverse commodities produced by the chemical industry is rapidly expanding globally. Accompanying this demand is an increased threat to the environment and to human health, due to waste produced by increased industrial production. This increased demand has underscored the necessity to increase reaction efficiencies, in order to reduce costs and increase profits. The discovery of novel biocatalysts is a key method aimed at combating these difficulties. Metagenomic technology, as a tool for uncovering novel biocatalysts, has great potential and applicability and has already delivered many successful achievements. In this review we discuss, recent developments and achievements in the field of biocatalysis. We highlight how green chemistry principles through the application of biocatalysis, can be successfully promoted and implemented in various industrial sectors. In addition, we demonstrate how two novel lipases/esterases were mined from the marine environment by metagenomic analysis. Collectively these improvements can result in increased efficiency, decreased energy consumption, reduced waste and cost savings for the chemical industry.}, }
@article {pmid29963639, year = {2018}, author = {Nieves-Ramírez, ME and Partida-Rodríguez, O and Laforest-Lapointe, I and Reynolds, LA and Brown, EM and Valdez-Salazar, A and Morán-Silva, P and Rojas-Velázquez, L and Morien, E and Parfrey, LW and Jin, M and Walter, J and Torres, J and Arrieta, MC and Ximénez-García, C and Finlay, BB}, title = {Asymptomatic Intestinal Colonization with Protist Blastocystis Is Strongly Associated with Distinct Microbiome Ecological Patterns.}, journal = {mSystems}, volume = {3}, number = {3}, pages = {}, pmid = {29963639}, issn = {2379-5077}, abstract = {Blastocystis is the most prevalent protist of the human intestine, colonizing approximately 20% of the North American population and up to 100% in some nonindustrialized settings. Blastocystis is associated with gastrointestinal and systemic disease but can also be an asymptomatic colonizer in large populations. While recent findings in humans have shown bacterial microbiota changes associated with this protist, it is unknown whether these occur due to the presence of Blastocystis or as a result of inflammation. To explore this, we evaluated the fecal bacterial and eukaryotic microbiota in 156 asymptomatic adult subjects from a rural population in Xoxocotla, Mexico. Colonization with Blastocystis was strongly associated with an increase in bacterial alpha diversity and broad changes in beta diversity and with more discrete changes to the microbial eukaryome. More than 230 operational taxonomic units (OTUs), including those of dominant species Prevotella copri and Ruminococcus bromii, were differentially abundant in Blastocystis-colonized individuals. Large functional changes accompanied these observations, with differential abundances of 202 (out of 266) predicted metabolic pathways (PICRUSt), as well as lower fecal concentrations of acetate, butyrate, and propionate in colonized individuals. Fecal calprotectin was markedly decreased in association with Blastocystis colonization, suggesting that this ecological shift induces subclinical immune consequences to the asymptomatic host. This work is the first to show a direct association between the presence of Blastocystis and shifts in the gut bacterial and eukaryotic microbiome in the absence of gastrointestinal disease or inflammation. These results prompt further investigation of the role Blastocystis and other eukaryotes play within the human microbiome. IMPORTANCE Given the results of our study and other reports of the effects of the most common human gut protist on the diversity and composition of the bacterial microbiome, Blastocystis and, possibly, other gut protists should be studied as ecosystem engineers that drive community diversity and composition.}, }
@article {pmid29963028, year = {2018}, author = {Petrova, MI and Macklaim, JM and Wuyts, S and Verhoeven, T and Vanderleyden, J and Gloor, GB and Lebeer, S and Reid, G}, title = {Comparative Genomic and Phenotypic Analysis of the Vaginal Probiotic Lactobacillus rhamnosus GR-1.}, journal = {Frontiers in microbiology}, volume = {9}, number = {}, pages = {1278}, pmid = {29963028}, issn = {1664-302X}, abstract = {Lactobacillus represents a versatile bacterial genus, which can adapt to a wide variety of ecological niches, including human body sites such as the intestinal and urogenital tract. In this study, the complete genome sequence of the vaginal probiotic Lactobacillus rhamnosus GR-1 was determined and compared to other L. rhamnosus strains at genomic and phenotypic level. The strain GR-1 was originally isolated from a female urethra, and was assessed with L. rhamnosus GG from a feces sample of a healthy male, and L. rhamnosus LC705 from a dairy product. A key difference is the absence in GR-1 and LC705 of the spaCBA locus required for pili-mediated intestinal epithelial adhesion. In addition, the L. rhamnosus GR-1 genome contains a unique cluster for exopolysaccharide production, which is postulated to synthesize glucose-rich, rhamnose-lacking exopolysaccharide molecules that are different from the galactose-rich extracellular polysaccharide of L. rhamnosus GG. Compared to L. rhamnosus GG, L. rhamnosus GR-1 was also genetically predicted and experimentally shown to better metabolize lactose and maltose, and to better withstand oxidative stress, which is of relevance in the vagina. This study could thus provide a molecular framework for the selection of the optimal probiotic strain for each targeted niche and condition, but further substantiation of niche adaptation mechanisms of lactobacilli is warranted.}, }
@article {pmid29962006, year = {2018}, author = {Jakobsen, TH and Eickhardt, SR and Gheorghe, AG and Stenqvist, C and Sønderholm, M and Stavnsberg, C and Jensen, P&#xd8; and Odgaard, A and Whiteley, M and Moser, C and Hvolris, J and Hougen, HP and Bjarnsholt, T}, title = {Implants induce a new niche for microbiomes.}, journal = {APMIS : acta pathologica, microbiologica, et immunologica Scandinavica}, volume = {126}, number = {8}, pages = {685-692}, doi = {10.1111/apm.12862}, pmid = {29962006}, issn = {1600-0463}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Bacteria/classification/*isolation &amp; purification ; Bacterial Typing Techniques ; Bone Regeneration/physiology ; Case-Control Studies ; Female ; Foreign Bodies/*microbiology ; Fractures, Bone/microbiology/surgery ; Fungi/classification/*isolation &amp; purification ; Humans ; Male ; Middle Aged ; Mycological Typing Techniques ; Prostheses and Implants/*microbiology ; Prosthesis Failure ; Prosthesis-Related Infections/*microbiology ; }, abstract = {Although much work is being done to develop new treatments, research and knowledge regarding factors underlying implant-related microbial colonization leading to infection are less comprehensive. Presence of microorganisms in and around implants clinically characterized as uninfected remains unknown. The objective of this study was to detect and identify bacteria and fungi on implants from various groups of patients with no prior indications of implant related infections. Patient samples (implants and tissue) were collected from five different hospitals in the Capital region of Denmark. By in-depth microbiological detection methods, we examined the prevalence of bacteria and fungi on 106 clinically uninfected implants from four patient groups (aseptic loosening, healed fractures, craniofacial complications and recently deceased). Of 106 clinically uninfected implants and 39 negative controls investigated, 66% were colonized by bacteria and 40% were colonized by fungi (p < 0.0001 compared to negative controls). A large number of microbes were found to colonize the implants, however, the most prevalent microbes present were not common aetiological agents of implant infections. The findings indicate that implants provide a distinct niche for microbial colonization. These data have broad implications for medical implant recipients, as well as for supporting the idea that the presence of foreign objects in the body alters the human microbiome by providing new colonization niches.}, }
@article {pmid29960810, year = {2019}, author = {Primec, M and Klemenak, M and Di Gioia, D and Aloisio, I and Bozzi Cionci, N and Quagliariello, A and Gorenjak, M and Mičetić-Turk, D and Langerholc, T}, title = {Clinical intervention using Bifidobacterium strains in celiac disease children reveals novel microbial modulators of TNF-α and short-chain fatty acids.}, journal = {Clinical nutrition (Edinburgh, Scotland)}, volume = {38}, number = {3}, pages = {1373-1381}, doi = {10.1016/j.clnu.2018.06.931}, pmid = {29960810}, issn = {1532-1983}, mesh = {*Bifidobacterium breve ; Celiac Disease/*drug therapy/*metabolism/microbiology ; Child ; Double-Blind Method ; Fatty Acids, Volatile/*metabolism ; Feces/microbiology ; Female ; *Gastrointestinal Microbiome ; Humans ; Male ; Probiotics/*therapeutic use ; Tumor Necrosis Factor-alpha/*blood ; }, abstract = {BACKGROUND &amp; AIMS: Celiac disease (CD) is an immune-mediated systemic disease, caused by ingestion of gluten in genetically predisposed individuals. Gut microbiota dysbiosis might play a significant role in pathogenesis of chronic enteropathies and its modulation can be used as an intervention strategy in CD as well. In this study, we aimed to identify correlations between fecal microbiota, serum tumor necrosis factor alpha (TNF-α) and fecal short-chain fatty acids (SCFAs) in healthy children and children with CD after administration of probiotic Bifidobacterium breve BR03 and B632.<br><br>METHODS: A double-blind placebo-controlled study enrolled 40 children with CD (CD) and 16 healthy children (HC). CD children were randomly allocated into two groups, of which 20 belonged to the placebo (PL) group and 20 to the Probiotic (PR) group. The PR group received a probiotic formulation containing a mixture of 2 strains, B.&#xa0;breve BR03 (DSM 16604) and B.&#xa0;breve B632 (DSM 24706) in 1:1 ratio for 3 months. Subsequently, for statistical analysis, blood and fecal samples from CD children (on enrolment - T0 and after 3 months, at the end of intervention with probiotic/placebo - T1) and HC children were used. The HC group was sampled only once (T0).<br><br>RESULTS: Verrucomicrobia, Parcubacteria and some yet unknown phyla of Bacteria and Archaea may be involved in the disease, indicated by a strong correlation to TNF-&#x3b1;. Likewise, Proteobacteria strongly correlated with fecal SCFAs concentration. The effect of probiotic administration has disclosed a negative correlation between Verrucomicrobia, some unknown phyla of Bacteria, Synergistetes, Euryarchaeota and some SCFAs, turning them into an important target in microbiome restoration process. Synergistetes and Euryarchaeota may have a role in the anti-inflammatory process in healthy human gut.<br><br>CONCLUSIONS: Our results highlight new phyla, which may have an important relation to disease-related parameters, CD itself and health.}, }
@article {pmid29951378, year = {2018}, author = {Scapaticci, M and Bartolini, A and Del Chierico, F and Accardi, C and Di Girolamo, F and Masotti, A and Muraca, M and Putignani, L}, title = {Phenotypic typing and epidemiological survey of antifungal resistance of Candida species detected in clinical samples of Italian patients in a 17 months' period.}, journal = {Germs}, volume = {8}, number = {2}, pages = {58-66}, pmid = {29951378}, issn = {2248-2997}, abstract = {INTRODUCTION: Yeast pathogens are emerging agents of nosocomial as well as community-acquired infections and their rapid and accurate identification is crucial for a better management of high-risk patients and for an adequate treatment.<br><br>METHODS: We performed a retrospective review of 156 yeast isolates collected during a 17 months' period of regular clinical practice at the Microbiology Department of San Camillo Hospital in Treviso, Italy and analyzed by the traditional culture-based method combined with matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS).<br><br>RESULTS: Out of all the samples collected MALDI-TOF MS was able to characterize with a MT score &#x2265;1.7 (accurate result at species level) 12 different yeast and yeast-like species from 140 samples: Candida albicans (63.7%), Candida glabrata (13.6%), Saccharomyces cerevisiae (6.5%), Candida parapsilosis (5.7%), Candida tropicalis (2.1%), Candida pararugosa (2.1%), Candida guilliermondii (2.1%), Candida kefyr (1.4%), Candida lusitaniae (0.7%), Candida palmioleophila (0.7%), Geotrichum silvicola (0.7%), Rhodotorula mucilaginosa (0.7%). Susceptibility testing toward seven common antifungal agents showed a characteristic MIC distribution of C. albicans isolates for echinocandins: particularly we noticed that 72% and 46% of C. albicans showed an MIC value close to clinical breakpoint as defined by EUCAST, respectively for anidulafungin and micafungin.<br><br>CONCLUSION: Accurate identification of microorganisms and the study of their antifungal susceptibility allow to understand the epidemiology of a particular area, permitting the choice of the most appropriate early antifungal treatment.}, }
@article {pmid29951086, year = {2018}, author = {Hadrich, D}, title = {Microbiome Research Is Becoming the Key to Better Understanding Health and Nutrition.}, journal = {Frontiers in genetics}, volume = {9}, number = {}, pages = {212}, pmid = {29951086}, issn = {1664-8021}, abstract = {The human microbiome has emerged as the crucial moderator in the interactions between food and our body. It is increasingly recognised that the microbiome can change our mind and health status, or switch on a wide range of diseases including cancer, cardio-metabolic diseases, allergies, and obesity. The causes of diseases are often only partially understood. However, nutrients, metabolites, and microbes are increasingly regarded as key players, even where the complete disease mechanisms remain unclear. The key to progress in the future will be to use and exploit additional, newly emerging disciplines such as metagenomics to complement patient information and to bring our understanding of diseases and the interrelation and effects of nutritional molecules to the next level. The EU has already funded 216 projects under the 7th Framework Programme and Horizon 2020 programmes to promote metagenomics and to advance our knowledge of microbes. This support started with the catalysing MetaHIT project that has produced a catalogue of gut microbes, and has arrived now at the very multi-disciplinary SYSCID action looking at how the microbiome is driving its resilience potential and our health. Together, these projects involve an investment of more than €498 M. However, in Horizon 2020, the new EU Health and Food Work Programmes for 2018-2020 go even further by setting new goals to find applications and to generate more knowledge on the microbiome, nutrition, various hosts of microbes, and their relation to health and disease. The big vision is to modulate health and diseases via the microbiome and nutrition, while at the same time other factors such as omics, molecular signatures, and lifestyle are constant. In this way, microbiome and nutrition research is moving from an isolated and despised offside position to a beacon of hope with a lot of potential and possibilities.}, }
@article {pmid29943448, year = {2018}, author = {Marchesi, JR}, title = {Advancing microbiome research.}, journal = {Immunology}, volume = {154}, number = {4}, pages = {535-536}, pmid = {29943448}, issn = {1365-2567}, }
@article {pmid29942682, year = {2018}, author = {Paul, C and Bayrychenko, Z and Junier, T and Filippidou, S and Beck, K and Bueche, M and Greub, G and Bürgmann, H and Junier, P}, title = {Dissemination of antibiotic resistance genes associated with the sporobiota in sediments impacted by wastewater.}, journal = {PeerJ}, volume = {6}, number = {}, pages = {e4989}, pmid = {29942682}, issn = {2167-8359}, abstract = {Aquatic ecosystems serve as a dissemination pathway and a reservoir of both antibiotic resistant bacteria (ARB) and antibiotic resistance genes (ARG). In this study, we investigate the role of the bacterial sporobiota to act as a vector for ARG dispersal in aquatic ecosystems. The sporobiota was operationally defined as the resilient fraction of the bacterial community withstanding a harsh extraction treatment eliminating the easily lysed fraction of the total bacterial community. The sporobiota has been identified as a critical component of the human microbiome, and therefore potentially a key element in the dissemination of ARG in human-impacted environments. A region of Lake Geneva in which the accumulation of ARG in the sediments has been previously linked to the deposition of treated wastewater was selected to investigate the dissemination of tet(W) and sul1, two genes conferring resistance to tetracycline and sulfonamide, respectively. Analysis of the abundance of these ARG within the sporobiome (collection of genes of the sporobiota) and correlation with community composition and environmental parameters demonstrated that ARG can spread across the environment with the sporobiota being the dispersal vector. A highly abundant OTU affiliated with the genus Clostridium was identified as a potential specific vector for the dissemination of tet(W), due to a strong correlation with tet(W) frequency (ARG copy numbers/ng DNA). The high dispersal rate, long-term survival, and potential reactivation of the sporobiota constitute a serious concern in terms of dissemination and persistence of ARG in the environment.}, }
@article {pmid29941067, year = {2018}, author = {Marchesi, JR}, title = {Advancing microbiome research.}, journal = {Microbiology (Reading, England)}, volume = {164}, number = {8}, pages = {1005-1006}, doi = {10.1099/mic.0.000688}, pmid = {29941067}, issn = {1465-2080}, mesh = {Biomedical Research/*methods ; High-Throughput Nucleotide Sequencing ; Humans ; Microbiota/*physiology ; }, }
@article {pmid29937405, year = {2018}, author = {Chang, CY and Yan, X and Crnovcic, I and Annaval, T and Chang, C and Nocek, B and Rudolf, JD and Yang, D and Hindra,  and Babnigg, G and Joachimiak, A and Phillips, GN and Shen, B}, title = {Resistance to Enediyne Antitumor Antibiotics by Sequestration.}, journal = {Cell chemical biology}, volume = {25}, number = {9}, pages = {1075-1085.e4}, pmid = {29937405}, issn = {2451-9448}, support = {R01 GM115575/GM/NIGMS NIH HHS/United States ; U01 GM098248/GM/NIGMS NIH HHS/United States ; R01 CA204484/CA/NCI NIH HHS/United States ; R01 CA078747/CA/NCI NIH HHS/United States ; U54 GM094585/GM/NIGMS NIH HHS/United States ; R01 GM109456/GM/NIGMS NIH HHS/United States ; }, mesh = {Anthraquinones/*chemistry/metabolism/*pharmacology ; Antibiotics, Antineoplastic/*chemistry/metabolism/*pharmacology ; Drug Resistance, Bacterial ; Enediynes/*chemistry/metabolism/*pharmacology ; Genes, Bacterial ; Humans ; Models, Molecular ; Multigene Family ; Streptomyces/drug effects/*genetics/metabolism ; }, abstract = {The enediynes, microbial natural products with extraordinary cytotoxicities, have been translated into clinical drugs. Two self-resistance mechanisms are known in the enediyne producers-apoproteins for the nine-membered enediynes and self-sacrifice proteins for the ten-membered enediyne calicheamicin. Here we show that: (1) tnmS1, tnmS2, and tnmS3 encode tiancimycin (TNM) resistance in its producer Streptomyces sp. CB03234, (2) tnmS1, tnmS2, and tnmS3 homologs are found in all anthraquinone-fused enediyne producers, (3) TnmS1, TnmS2, and TnmS3 share a similar β barrel-like structure, bind TNMs with nanomolar KD values, and confer resistance by sequestration, and (4) TnmS1, TnmS2, and TnmS3 homologs are widespread in nature, including in the human microbiome. These findings unveil an unprecedented resistance mechanism for the enediynes. Mechanisms of self-resistance in producers serve as models to predict and combat future drug resistance in clinical settings. Enediyne-based chemotherapies should now consider the fact that the human microbiome harbors genes encoding enediyne resistance.}, }
@article {pmid29931340, year = {2018}, author = {van Dijkhuizen, EHP and Aidonopoulos, O and Ter Haar, NM and Pires Marafon, D and Magni-Manzoni, S and Ioannidis, YE and Putignani, L and Vastert, SJ and Malattia, C and De Benedetti, F and Martini, A}, title = {Prediction of inactive disease in juvenile idiopathic arthritis: a multicentre observational cohort study.}, journal = {Rheumatology (Oxford, England)}, volume = {57}, number = {10}, pages = {1752-1760}, doi = {10.1093/rheumatology/key148}, pmid = {29931340}, issn = {1462-0332}, mesh = {*Algorithms ; Arthritis, Juvenile/*pathology ; Child ; Child, Preschool ; Female ; Humans ; Male ; Predictive Value of Tests ; Prognosis ; Prospective Studies ; *Severity of Illness Index ; }, abstract = {OBJECTIVES: To predict the occurrence of inactive disease in JIA in the first 2 years of disease.<br><br>METHODS: An inception cohort of 152 treatment-na&#xef;ve JIA patients with disease duration <6 months was analysed. Potential predictors were baseline clinical variables, joint US, gut microbiota composition and a panel of inflammation-related compounds in blood plasma. Various algorithms were employed to predict inactive disease according to Wallace criteria at 6-month intervals in the first 2 years. Performance of the models was evaluated using the split-cohort technique. The cohort was analysed in its entirety, and separate models were developed for oligoarticular patients, polyarticular RF negative patients and ANA positive patients.<br><br>RESULTS: All models analysing the cohort as a whole showed poor performance in test data [area under the curve (AUC): <0.65]. The subgroup models performed better. Inactive disease was predicted by lower baseline juvenile arthritis DAS (JADAS)-71 and lower relative abundance of the operational taxonomic unit Mogibacteriaceae for oligoarticular patients (AUC in test data: 0.69); shorter duration of morning stiffness, higher haemoglobin and lower CXCL-9 levels at baseline for polyarticular RF negative patients (AUC in test data: 0.69); and shorter duration of morning stiffness and higher baseline haemoglobin for ANA positive patients (AUC in test data: 0.72).<br><br>CONCLUSION: Inactive disease could not be predicted with satisfactory accuracy in the whole cohort, likely due to disease heterogeneity. Interesting predictors were found in more homogeneous subgroups. These need to be validated in future studies.}, }
@article {pmid29927545, year = {2018}, author = {Bäumel, S and Tytgat, HLP and Nemec, B and Schmidt, R and Chia, LW and Smidt, H}, title = {Fifty Percent Human - how art brings us in touch with our microbial cohabitants.}, journal = {Microbial biotechnology}, volume = {11}, number = {4}, pages = {571-574}, pmid = {29927545}, issn = {1751-7915}, mesh = {*Art ; Creativity ; Ecosystem ; Humans ; *Microbiota ; Philosophy ; }, abstract = {The Human Microbiome, as well as the exploration of the microorganisms inhabiting the human body, are not only integral to the field of microbiology but represent an intrinsic part of all human beings. Consequently, along with scientists, artists have been inspired by the microbiome: transforming it in to tangible artefacts in order to critically question, reflect on and break down the barrier between humans and their microcohabitants. By artistic means, artists help us to understand how microbial research topics are inevitably affected by societal influences, including (health) politics, economics and the arts. Fifty Percent Human is a multidisciplinary artistic research project that aims to reshape our understanding of the human body and its environment as well as to explore possibilities for conscious coexistence in order to bridge the gap between science and society.}, }
@article {pmid29922272, year = {2018}, author = {Del Chierico, F and Abbatini, F and Russo, A and Quagliariello, A and Reddel, S and Capoccia, D and Caccamo, R and Ginanni Corradini, S and Nobili, V and De Peppo, F and Dallapiccola, B and Leonetti, F and Silecchia, G and Putignani, L}, title = {Gut Microbiota Markers in Obese Adolescent and Adult Patients: Age-Dependent Differential Patterns.}, journal = {Frontiers in microbiology}, volume = {9}, number = {}, pages = {1210}, pmid = {29922272}, issn = {1664-302X}, abstract = {Obesity levels, especially in children, have dramatically increased over the last few decades. Recently, several studies highlighted the involvement of gut microbiota in the pathophysiology of obesity. We investigated the composition of gut microbiota in obese adolescents and adults compared to age-matched normal weight (NW) volunteers in order to assemble age- and obesity-related microbiota profiles. The composition of gut microbiota was analyzed by 16S rRNA-based metagenomics. Ecological representations of microbial communities were computed, and univariate, multivariate, and correlation analyses performed on bacterial profiles. The prediction of metagenome functional content from 16S rRNA gene surveys was carried out. Ecological analyses revealed a dissimilarity among the subgroups, and resultant microbiota profiles differed between obese adolescents and adults. Using statistical analyses, we assigned, as microbial markers, Faecalibacterium prausnitzii and Actinomyces to the microbiota of obese adolescents, and Parabacteroides, Rikenellaceae, Bacteroides caccae, Barnesiellaceae, and Oscillospira to the microbiota of NW adolescents. The predicted metabolic profiles resulted different in adolescent groups. Particularly, biosynthesis of primary bile acid and steroid acids, metabolism of fructose, mannose, galactose, butanoate, and pentose phosphate and glycolysis/gluconeogenesis were for the majority associated to obese, while biosynthesis and metabolism of glycan, biosynthesis of secondary bile acid, metabolism of steroid hormone and lipoic acid were associated to NW adolescents. Our study revealed unique features of gut microbiota in terms of ecological patterns, microbial composition and metabolism in obese patients. The assignment of novel obesity bacterial markers may open avenues for the development of patient-tailored treatments dependent on age-related microbiota profiles.}, }
@article {pmid29917039, year = {2019}, author = {Noguera-Julian, M and González-Beiras, C and Parera, M and Ubals, M and Kapa, A and Paredes, R and Mitjà, O}, title = {Etiological Characterization of the Cutaneous Ulcer Syndrome in Papua New Guinea Using Shotgun Metagenomics.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {68}, number = {3}, pages = {482-489}, doi = {10.1093/cid/ciy502}, pmid = {29917039}, issn = {1537-6591}, mesh = {Adolescent ; Bacteria/classification/genetics/*isolation &amp; purification ; Child ; Coinfection/epidemiology/etiology ; Female ; Humans ; Male ; Metagenomics/methods ; Papua New Guinea/epidemiology ; Prospective Studies ; Sequence Analysis, DNA ; Skin Diseases, Bacterial/*epidemiology/*etiology ; Ulcer/*epidemiology/*etiology ; }, abstract = {BACKGROUND: Treponema pallidum subsp pertenue and Haemophilus ducreyi are causative agents of cutaneous ulcer (CU) in yaws-endemic regions in the tropics. However, a significant proportion of CU patients remain polymerase chain reaction (PCR) negative for both bacterial agents. We aimed to identify potential additional etiological agents of CU in a yaws-endemic region.<br><br>METHODS: This population-based cohort study included children in Lihir Island (Papua New Guinea) examined during a yaws eradication campaign in October 2013-October 2014. All consenting patients with atraumatic exudative ulcers of >1 cm diameter were enrolled. Lesional swabs were collected for real-time PCR testing for T. pallidum subsp pertenue and H. ducreyi. We then performed shotgun whole DNA metagenomics sequencing on extracted DNA and taxonomically assigned shotgun sequences using a human microbiome reference.<br><br>RESULTS: Sequence data were available for 122 samples. Shotgun sequencing showed high classification agreement relative to PCR testing (area under the curve for T. pallidum/H. ducreyi was 0.92/0.85, respectively). Clustering analysis of shotgun data revealed compositional clusters where the dominant species (median relative abundance ranged from 32% to 66%) was H. ducreyi (23% of specimens), T. pallidum subsp pertenue (16%), Streptococcus dysgalactiae (12%), Arcanobacterium haemolyticum (8%), and Corynebacterium diphtheriae (8%). Sample clustering derived from ulcer microbial composition did not show geographical patterns.<br><br>CONCLUSIONS: These data suggest a diverse etiology of skin ulcers in yaws-endemic areas, which may help design more accurate diagnostic tools and more effective antimicrobial treatment approaches to the cutaneous ulcer syndrome.}, }
@article {pmid29915115, year = {2018}, author = {Shen, M and Yang, Y and Shen, W and Cen, L and McLean, JS and Shi, W and Le, S and He, X}, title = {A Linear Plasmid-Like Prophage of Actinomyces odontolyticus Promotes Biofilm Assembly.}, journal = {Applied and environmental microbiology}, volume = {84}, number = {17}, pages = {}, pmid = {29915115}, issn = {1098-5336}, support = {R01 DE020102/DE/NIDCR NIH HHS/United States ; R01 DE023810/DE/NIDCR NIH HHS/United States ; R01 DE026186/DE/NIDCR NIH HHS/United States ; }, mesh = {Actinomyces/*growth &amp; development/isolation &amp; purification/*virology ; Biofilms/*growth &amp; development ; Genome, Bacterial/genetics ; Genome, Viral/genetics ; Humans ; Lysogeny/genetics ; Microscopy, Electron, Transmission ; Mouth/microbiology ; Phylogeny ; Plasmids/genetics ; Prophages/*classification/*genetics/isolation &amp; purification ; Siphoviridae/classification/genetics/isolation &amp; purification ; }, abstract = {The human oral cavity is home to a large number of bacteria and bacteriophages (phages). However, the biology of oral phages as members of the human microbiome is not well understood. Recently, we isolated Actinomyces odontolyticus subsp. actinosynbacter strain XH001 from the human oral cavity, and genomic analysis revealed the presence of an intact prophage named xhp1. Here, we demonstrated that xhp1 is a linear plasmid-like prophage, which is a newly identified phage of A. odontolyticus The prophage xhp1 genome is a 35-kb linear double-stranded DNA with 10-bp single-stranded, 3' cohesive ends. xhp1 exists extrachromosomally, with an estimated copy number of 5. Annotation of xhp1 revealed 54 open reading frames, while phylogenetic analysis suggests that it has limited similarity with other phages. xhp1 phage particles can be induced by mitomycin C and belong to the Siphoviridae family, according to transmission electron microscopic examination. The released xhp1 particles can reinfect the xhp1-cured XH001 strain and result in tiny blurry plaques. Moreover, xhp1 promotes XH001 biofilm formation through spontaneous induction and the release of host extracellular DNA (eDNA). In conclusion, we identified a linear plasmid-like prophage of A. odontolyticus, which enhances bacterial host biofilm assembly and could be beneficial to the host for its persistence in the oral cavity.IMPORTANCE The biology of phages as members of the human oral microbiome is understudied. Here, we report the characterization of xhp1, a novel linear plasmid-like prophage identified from a human oral isolate, Actinomyces odontolyticus subsp. actinosynbacter strain XH001. xhp1 can be induced and reinfect xhp1-cured XH001. The spontaneous induction of xhp1 leads to the lysis of a subpopulation of bacterial hosts and the release of eDNA that promotes biofilm assembly, thus potentially contributing to the persistence of A. odontolyticus within the oral cavity.}, }
@article {pmid29913479, year = {2018}, author = {Ismail, T and Fatima, N and Muhammad, SA and Zaidi, SS and Rehman, N and Hussain, I and Tariq, NUS and Amirzada, I and Mannan, A}, title = {Prioritizing and modelling of putative drug target proteins of Candida albicans by systems biology approach.}, journal = {Acta biochimica Polonica}, volume = {65}, number = {2}, pages = {209-218}, doi = {10.18388/abp.2017_2327}, pmid = {29913479}, issn = {1734-154X}, mesh = {Antifungal Agents/pharmacology ; Candida albicans/*chemistry/drug effects ; Fungal Proteins/analysis/*genetics ; Humans ; Models, Molecular ; Molecular Docking Simulation ; Subcellular Fractions/chemistry ; Systems Biology/*methods ; }, abstract = {Candida albicans (Candida albicans) is one of the major sources of nosocomial infections in humans which may prove fatal in 30% of cases. The hospital acquired infection is very difficult to treat affectively due to the presence of drug resistant pathogenic strains, therefore there is a need to find alternative drug targets to cure this infection. In silico and computational level frame work was used to prioritize and establish antifungal drug targets of Candida albicans. The identification of putative drug targets was based on acquiring 5090 completely annotated genes of Candida albicans from available databases which were categorized into essential and non-essential genes. The result indicated that 9% of proteins were essential and could become potential candidates for intervention which might result in pathogen eradication. We studied cluster of orthologs and the subtractive genomic analysis of these essential proteins against human genome was made as a reference to minimize the side effects. It was seen that 14% of Candida albicans proteins were evolutionary related to the human proteins while 86% are non-human homologs. In the next step of compatible drug target selections, the non-human homologs were sequentially compared to the human microbiome data to minimize the potential effects against gut flora which accumulated to 38% of the essential genome. The sub-cellular localization of these candidate proteins in fungal cellular systems indicated that 80% of them are cytoplasmic, 10% are mitochondrial and the remaining 10% are associated with the cell wall. The role of these non-human and non-gut flora putative target proteins in Candida albicans biological pathways was studied. Due to their integrated and critical role in Candida albicans replication cycle, four proteins were selected for molecular modeling. For drug designing and development, four high quality and reliable protein models with more than 70% sequence identity were constructed. These proteins are used for the docking studies of the known and new ligands (unpublished data). Our study will be an effective framework for drug target identifications of pathogenic microbial strains and development of new therapies against the infections they cause.}, }
@article {pmid29913309, year = {2018}, author = {Schirmer, M and Kumar, V and Netea, MG and Xavier, RJ}, title = {The causes and consequences of variation in human cytokine production in health.}, journal = {Current opinion in immunology}, volume = {54}, number = {}, pages = {50-58}, doi = {10.1016/j.coi.2018.05.012}, pmid = {29913309}, issn = {1879-0372}, mesh = {B-Lymphocytes/immunology ; Cytokines/*biosynthesis/*immunology ; *Health ; Humans ; Immune System Diseases/immunology ; T-Lymphocytes, Regulatory/immunology ; }, abstract = {Cytokines are important cell-signaling molecules that activate and modulate immune responses. Major factors influencing cytokine variation in healthy individuals are host genetics, non-heritable factors and the microbiome. Genetic variation accounts for a significant part of heterogeneity in cytokine production by peripheral blood mononuclear cells. Variation in cytokines such as IL-6 and IL-6Ra is strongly influenced by heritability, suggesting an evolutionarily pressure for their genetic regulation that potentially contributes to differences in immune responsiveness between human populations. Non-heritable factors, including age, body weight and environmental variables such as seasonality, drive variation in baseline cytokine levels. Age further affects pathogen-induced lymphocyte-derived cytokine responses, whereas seasonality affects monocyte-derived cytokine production in response to influenza virus, Coxiella burnetti or Cryptococcus neoformans. Another influential factor that shapes the immune system is the human microbiome. Microbes and microbial products (e.g. short-chain fatty acids and tryptophan metabolites) possess strong immunomodulatory effects, induce regulatory T cells and lead to the diversification of B cells and the production of specific antibodies. In particular, differential TNFα and IFNγ production is associated with the gut microbiome. Understanding causes of variation in the healthy human immune system can reveal factors that lead to aberrant cytokine production in immune-related disorders.}, }
@article {pmid29912913, year = {2018}, author = {McMillan, A and Rulisa, S and Gloor, GB and Macklaim, JM and Sumarah, M and Reid, G}, title = {Pilot assessment of probiotics for pregnant women in Rwanda.}, journal = {PloS one}, volume = {13}, number = {6}, pages = {e0195081}, pmid = {29912913}, issn = {1932-6203}, support = {227328//Canadian Institute Health Research/International ; }, mesh = {Adolescent ; Adult ; Female ; Humans ; *Lacticaseibacillus rhamnosus ; *Microbiota ; Middle Aged ; Pilot Projects ; Pregnancy ; Probiotics/*administration &amp; dosage ; Rwanda ; Vagina/*microbiology ; }, abstract = {BACKGROUND: While the global market for probiotics is soon to reach in excess of US$50 billion, the continent of Africa has been largely ignored, despite these products having the ability to reduce the burden of disease and death.<br><br>TRIAL DESIGN: The present randomised, blinded, placebo-controlled clinical trial was undertaken in Rwanda, a country devoid of well-documented probiotics. The primary outcome aim was to examine receptivity and compliance for orally administered probiotic capsules containing Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri RC-14 in pregnant women and assess any initial side effects or changes to the vaginal microbiome.<br><br>METHODS: Pregnant women between the ages of 18 and 55 were recruited from the Nyamata District Hospital in Rwanda and randomly assigned to receive probiotic or placebo capsules for one month. Clinicians were blinded to the treatments.<br><br>RESULTS: The drop-out rate was 21%, with 13 of 18 women in the placebo group and 17 of 20 in the probiotic group completing the study. Only 13 women returned for birthing and additional sample collection. No side effects of either treatment group were reported. Microbiota and metabolomics data showed similar findings to those reported in the literature, with low bacterial diversity and Lactobacillus dominance associated with a healthy vagina, and birthing associated with high diversity. Despite the small sample size and lack of changes in the microbiota, women in the placebo arm were significantly more likely to give birth pre-term.<br><br>CONCLUSION: Overall women were receptive to the probiotic concept, but the lack of information on such products and logistical and economical challenges pose problems for wider population engagement.<br><br>TRIAL REGISTRATION: ClinicalTrials.gov NCT02150655.}, }
@article {pmid29910789, year = {2018}, author = {Pannaraj, PS and Ly, M and Cerini, C and Saavedra, M and Aldrovandi, GM and Saboory, AA and Johnson, KM and Pride, DT}, title = {Shared and Distinct Features of Human Milk and Infant Stool Viromes.}, journal = {Frontiers in microbiology}, volume = {9}, number = {}, pages = {1162}, pmid = {29910789}, issn = {1664-302X}, support = {K23 HD072774/HD/NICHD NIH HHS/United States ; }, abstract = {Infants acquire many of their microbes from their mothers during the birth process. The acquisition of these microbes is believed to be critical in the development of the infant immune system. Bacteria also are transmitted to the infant through breastfeeding, and help to form the microbiome of the infant gastrointestinal (GI) tract; it is unknown whether viruses in human milk serve to establish an infant GI virome. We examined the virome contents of milk and infant stool in a cohort of mother-infant pairs to discern whether milk viruses colonize the infant GI tract. We observed greater viral alpha diversity in milk than in infant stool, similar to the trend we found for bacterial communities from both sites. When comparing beta diversity, viral communities were mostly distinguishable between milk and infant stool, but each was quite distinct from adult stool, urine, and salivary viromes. There were significant differences in viral families in the infant stool (abundant bacteriophages from the family Siphoviridae) compared to milk (abundant bacteriophages from the family Myoviridae), which may reflect significant differences in the bacterial families identified from both sites. Despite the differences in viral taxonomy, we identified a significant number of shared viruses in the milk and stool from all mother-infant pairs. Because of the significant proportion of bacteriophages transmitted in these mother-infant pairs, we believe the transmission of milk phages to the infant GI tract may help to shape the infant GI microbiome.}, }
@article {pmid29908759, year = {2018}, author = {Qiu, B and Al, K and Pena-Diaz, AM and Athwal, GS and Drosdowech, D and Faber, KJ and Burton, JP and O'Gorman, DB}, title = {Cutibacterium acnes and the shoulder microbiome.}, journal = {Journal of shoulder and elbow surgery}, volume = {27}, number = {10}, pages = {1734-1739}, doi = {10.1016/j.jse.2018.04.019}, pmid = {29908759}, issn = {1532-6500}, mesh = {Acinetobacter/*isolation &amp; purification ; Adolescent ; Adult ; Aged ; Cartilage, Articular/microbiology ; DNA, Bacterial/*analysis ; Gram-Positive Bacterial Infections/microbiology ; Humans ; Ligaments, Articular/microbiology ; Microbiota ; Middle Aged ; Propionibacterium acnes/*isolation &amp; purification ; RNA, Ribosomal, 16S/*analysis ; Rotator Cuff/microbiology ; Shoulder/*microbiology ; Shoulder Joint/surgery ; Skin/microbiology ; Subcutaneous Fat/microbiology ; Young Adult ; }, abstract = {BACKGROUND: Advances in DNA sequencing technologies have made it possible to detect microbial genome sequences (microbiomes) within tissues once thought to be sterile. We used this approach to gain insights into the likely sources of Cutibacterium acnes (formerly Propionibacterium acnes) infections within the shoulder.<br><br>METHODS: Tissue samples were collected from the skin, subcutaneous fat, anterior supraspinatus tendon, middle glenohumeral ligament, and humeral head cartilage of 23 patients (14 male and 9 female patients) during primary arthroplasty surgery. Total DNA was extracted and microbial 16S ribosomal RNA sequencing was performed using an Illumina MiSeq system. Data analysis software was used to generate operational taxonomic units for quantitative and statistical analyses.<br><br>RESULTS: After stringent removal of contamination, genomic DNA from various Acinetobacter species and from the Oxalobacteraceae family was identified in 74% of rotator cuff tendon tissue samples. C acnes DNA was detected in the skin of 1 male patient but not in any other shoulder tissues.<br><br>CONCLUSION: Our findings indicate the presence of a low-abundance microbiome in the rotator cuff and, potentially, in other shoulder tissues. The absence of C acnes DNA in all shoulder tissues assessed other than the skin is consistent with the hypothesis that C acnes infections are derived from skin contamination during surgery and not from opportunistic expansion of a resident C acnes population in the shoulder joint.}, }
@article {pmid29908580, year = {2018}, author = {Ely, PH}, title = {Is psoriasis a bowel disease? Successful treatment with bile acids and bioflavonoids suggests it is.}, journal = {Clinics in dermatology}, volume = {36}, number = {3}, pages = {376-389}, doi = {10.1016/j.clindermatol.2018.03.011}, pmid = {29908580}, issn = {1879-1131}, mesh = {Animals ; Anti-Bacterial Agents/therapeutic use ; Bacterial Translocation ; Bile Acids and Salts/*therapeutic use ; Biological Variation, Individual ; Diet ; Endotoxemia/complications/drug therapy ; Endotoxins/*metabolism ; Flavonoids/*therapeutic use ; *Gastrointestinal Microbiome ; Gastrointestinal Tract/immunology ; Helicobacter Infections/complications/drug therapy ; Helicobacter pylori ; Humans ; Peptidoglycan/*metabolism ; Psoriasis/*drug therapy/*microbiology ; }, abstract = {The gut is the largest lymphoid organ in the body. The human microbiome is composed of trillions of bacteria. The DNA of these bacteria dwarfs the human genome. Diet and ethanol can cause rapid shifts in the number and types of bacteria in the gut. The psoriatic microbiome is similar to that seen in alcoholics; there is a decrease in bacterial diversity and overgrowth of bacteria in the small bowel. Psoriatics often have liver disease and deficiencies in bile acids. Psoriasis is a disease characterized by a leaky gut. All of the comorbidities of this disease are due to systemic endotoxemia. Bacterial peptidoglycans absorbed from the gut have direct toxic effects on the liver and skin. Their absorption, as well as endotoxin absorption, must be eliminated to treat psoriasis successfully. Endotoxin absorption is markedly increased by ethanol and peppers. Bioflavonoids, such as quercetin and citrus bioflavonoids, prevent this absorption. Bile acids, given orally, break up endotoxin in the intestinal lumen. Pathogens, including Helicobacter pylori and Streptococcus pyogenes, must be eliminated with antimicrobial therapy for any treatment to work. A complete protocol for curing psoriasis is provided.}, }
@article {pmid29902438, year = {2018}, author = {Milshteyn, A and Colosimo, DA and Brady, SF}, title = {Accessing Bioactive Natural Products from the Human Microbiome.}, journal = {Cell host &amp; microbe}, volume = {23}, number = {6}, pages = {725-736}, pmid = {29902438}, issn = {1934-6069}, support = {R01 AT009562/AT/NCCIH NIH HHS/United States ; }, mesh = {Anti-Bacterial Agents/metabolism ; Bacteria/genetics/metabolism ; Biological Products/*metabolism/*pharmacology ; Humans ; Indoles/metabolism ; Metabolomics ; Metagenomics ; Microbial Interactions ; Microbiota/genetics/*physiology ; Multigene Family ; Peptides, Cyclic/metabolism ; Pyrrolidonecarboxylic Acid/metabolism ; Thiazolidines/metabolism ; }, abstract = {Natural products have long played a pivotal role in the development of therapeutics for a variety of diseases. Traditionally, soil and marine environments have provided a rich reservoir from which diverse chemical scaffolds could be discovered. Recently, the human microbiome has been recognized as a promising niche from which secondary metabolites with therapeutic potential have begun to be isolated. In this Review, we address how the expansive history of identifying bacterial natural products in other environments is informing the approaches being brought to bear on the study of the human microbiota. We also touch on how these tools can lead to insights about microbe-microbe and host-microbe interactions and help generate biological hypotheses that may lead to developments of new therapeutic modalities.}, }
@article {pmid29900563, year = {2018}, author = {Coleman, M and Elkins, C and Gutting, B and Mongodin, E and Solano-Aguilar, G and Walls, I}, title = {Microbiota and Dose Response: Evolving Paradigm of Health Triangle.}, journal = {Risk analysis : an official publication of the Society for Risk Analysis}, volume = {38}, number = {10}, pages = {2013-2028}, doi = {10.1111/risa.13121}, pmid = {29900563}, issn = {1539-6924}, mesh = {Animals ; *Bacteria ; *Dysbiosis ; *Gastrointestinal Microbiome ; Genomics ; Humans ; Immunity, Innate ; Immunity, Mucosal ; Intestines/immunology/microbiology ; Mice ; Models, Biological ; Prebiotics ; Probiotics/*analysis ; Risk Assessment/*methods ; }, abstract = {SRA Dose-Response and Microbial Risk Analysis Specialty Groups jointly sponsored symposia that addressed the intersections between the "microbiome revolution" and dose response. Invited speakers presented on innovations and advances in gut and nasal microbiota (normal microbial communities) in the first decade after the Human Microbiome Project began. The microbiota and their metabolites are now known to influence health and disease directly and indirectly, through modulation of innate and adaptive immune systems and barrier function. Disruption of healthy microbiota is often associated with changes in abundance and diversity of core microbial species (dysbiosis), caused by stressors including antibiotics, chemotherapy, and disease. Nucleic-acid-based metagenomic methods demonstrated that the dysbiotic host microbiota no longer provide normal colonization resistance to pathogens, a critical component of innate immunity of the superorganism. Diverse pathogens, probiotics, and prebiotics were considered in human and animal models (in vivo and in vitro). Discussion included approaches for design of future microbial dose-response studies to account for the presence of the indigenous microbiota that provide normal colonization resistance, and the absence of the protective microbiota in dysbiosis. As NextGen risk analysis methodology advances with the "microbiome revolution," a proposed new framework, the Health Triangle, may replace the old paradigm based on the Disease Triangle (focused on host, pathogen, and environment) and germophobia. Collaborative experimental designs are needed for testing hypotheses about causality in dose-response relationships for pathogens present in our environments that clearly compete in complex ecosystems with thousands of bacterial species dominating the healthy superorganism.}, }
@article {pmid29899737, year = {2018}, author = {Xun, Z and Zhang, Q and Xu, T and Chen, N and Chen, F}, title = {Dysbiosis and Ecotypes of the Salivary Microbiome Associated With Inflammatory Bowel Diseases and the Assistance in Diagnosis of Diseases Using Oral Bacterial Profiles.}, journal = {Frontiers in microbiology}, volume = {9}, number = {}, pages = {1136}, pmid = {29899737}, issn = {1664-302X}, abstract = {Inflammatory bowel diseases (IBDs) are chronic, idiopathic, relapsing disorders of unclear etiology affecting millions of people worldwide. Aberrant interactions between the human microbiota and immune system in genetically susceptible populations underlie IBD pathogenesis. Despite extensive studies examining the involvement of the gut microbiota in IBD using culture-independent techniques, information is lacking regarding other human microbiome components relevant to IBD. Since accumulated knowledge has underscored the role of the oral microbiota in various systemic diseases, we hypothesized that dissonant oral microbial structure, composition, and function, and different community ecotypes are associated with IBD; and we explored potentially available oral indicators for predicting diseases. We examined the 16S rRNA V3-V4 region of salivary bacterial DNA from 54 ulcerative colitis (UC), 13 Crohn's disease (CD), and 25 healthy individuals using Illumina sequencing. Distinctive sample clusters were driven by disease or health based on principal coordinate analysis (PCoA) of both the Operational Taxonomic Unit profile and Kyoto Encyclopedia of Genes and Genomes pathways. Comparisons of taxa abundances revealed enrichment of Streptococcaceae (Streptococcus) and Enterobacteriaceae in UC and Veillonellaceae (Veillonella) in CD, accompanied by depletion of Lachnospiraceae and [Prevotella] in UC and Neisseriaceae (Neisseria) and Haemophilus in CD, most of which have been demonstrated to exhibit the same variation tendencies in the gut of IBD patients. IBD-related oral microorganisms were associated with white blood cells, reduced basic metabolic processes, and increased biosynthesis and transport of substances facilitating oxidative stress and virulence. Furthermore, UC and CD communities showed robust sub-ecotypes that were not demographic or severity-specific, suggesting their value for future applications in precision medicine. Additionally, indicator species analysis revealed several genera indicative of UC and CD, which were confirmed in a longitudinal cohort. Collectively, this study demonstrates evident salivary dysbiosis and different ecotypes in IBD communities and provides an option for identifying at-risk populations, not only enhancing our understanding of the IBD microbiome apart from the gut but also offering a clinically useful strategy to track IBD as saliva can be sampled conveniently and non-invasively.}, }
@article {pmid29898981, year = {2018}, author = {Bansal, S and Nguyen, JP and Leligdowicz, A and Zhang, Y and Kain, KC and Ricciuto, DR and Coburn, B}, title = {Rectal and Naris Swabs: Practical and Informative Samples for Analyzing the Microbiota of Critically Ill Patients.}, journal = {mSphere}, volume = {3}, number = {3}, pages = {}, pmid = {29898981}, issn = {2379-5042}, support = {FDN-14839//CIHR/Canada ; }, mesh = {Cluster Analysis ; *Critical Illness ; DNA, Ribosomal/chemistry/genetics ; Feces/microbiology ; Humans ; Intensive Care Units ; *Microbiota ; Nose/*microbiology ; Phylogeny ; RNA, Ribosomal, 16S/genetics ; Rectum/*microbiology ; Sequence Analysis, DNA ; Skin/microbiology ; }, abstract = {Commensal microbiota are immunomodulatory, and their pathological perturbation can affect the risk and outcomes of infectious and inflammatory diseases. Consequently, the human microbiota is an emerging diagnostic and therapeutic target in critical illness. In this study, we compared four sample types-rectal, naris, and antecubital swabs and stool samples-for 16S rRNA gene microbiota sequencing in intensive care unit (ICU) patients. Stool samples were obtained in only 31% of daily attempts, while swabs were reliably obtained (≥97% of attempts). Swabs were compositionally distinct by anatomical site, and rectal swabs identified within-patient temporal trends in microbiota composition. Rectal swabs from ICU patients demonstrated differences from healthy stool similar to those observed in comparing stool samples from ICU patients to those from the same healthy controls. Rectal swabs are a useful complement to other sample types for analysis of the intestinal microbiota in critical illness, particularly when obtaining stool may not be feasible or practical.IMPORTANCE Perturbation of the microbiome has been correlated with various infectious and inflammatory diseases and is common in critically ill patients. Stool is typically used to sample the microbiota in human observational studies; however, it is often unavailable for collection from critically ill patients, reducing its utility as a sample type to study this population. Our research identified alternatives to stool for sampling the microbiota during critical illness. Rectal and naris swabs were practical alternatives for use in these patients, as they were observed to be more reliably obtained than stool, were suitable for culture-independent analysis, and successfully captured within- and between-patient microbiota differences.}, }
@article {pmid29896176, year = {2018}, author = {Elbehery, AHA and Feichtmayer, J and Singh, D and Griebler, C and Deng, L}, title = {The Human Virome Protein Cluster Database (HVPC): A Human Viral Metagenomic Database for Diversity and Function Annotation.}, journal = {Frontiers in microbiology}, volume = {9}, number = {}, pages = {1110}, pmid = {29896176}, issn = {1664-302X}, abstract = {Human virome, including those of bacteria (bacteriophages) have received an increasing attention recently, owing to the rapid developments in human microbiome research and the awareness of the far-reaching influence of microbiomes on health and disease. Nevertheless, human viromes are still underrepresented in literature making viruses a virtually untapped resource of diversity, functional and physiological information. Here we present the human virome protein cluster database as an effort to improve functional annotation and characterization of human viromes. The database was built out of hundreds of virome datasets from six different body sites. We also show the utility of this database through its use for the characterization of three bronchoalveolar lavage (BAL) viromes from one healthy control in addition to one moderate and one severe chronic obstructive pulmonary disease (COPD) patients. The use of the database allowed for a better functional annotation, which were otherwise poorly characterized when limited to annotation using sequences from full-length viral genomes. In addition, our BAL samples gave a first insight into viral communities of COPD patients and confirm a state of dysbiosis for viruses that increases with disease progression. Moreover, they shed light on the potential role of phages in the horizontal gene transfer of bacterial virulence factors, a phenomenon that highlights a possible contribution of phages to etiopathology.}, }
@article {pmid29895255, year = {2019}, author = {Katsi, V and Didagelos, M and Skevofilax, S and Armenis, I and Kartalis, A and Vlachopoulos, C and Karvounis, H and Tousoulis, D}, title = {GUT Microbiome-GUT Dysbiosis-Arterial Hypertension: New Horizons.}, journal = {Current hypertension reviews}, volume = {15}, number = {1}, pages = {40-46}, doi = {10.2174/1573402114666180613080439}, pmid = {29895255}, issn = {1875-6506}, mesh = {Animals ; Antihypertensive Agents/therapeutic use ; *Arterial Pressure/drug effects ; Bacteria/drug effects/*growth &amp; development ; Disease Models, Animal ; Dysbiosis ; *Gastrointestinal Microbiome/drug effects ; Host-Pathogen Interactions ; Humans ; Hypertension/drug therapy/epidemiology/*microbiology/*physiopathology ; Intestines/*microbiology ; Probiotics/therapeutic use ; Risk Factors ; }, abstract = {Arterial hypertension is a progressive cardiovascular syndrome arising from complex and interrelated etiologies. The human microbiome refers to the community of microorganisms that live in or on the human body. They influence human physiology by interfering in several processes such as providing nutrients and vitamins in Phase I and Phase II drug metabolism. The human gut microbiota is represented mainly by Firmicutes and Bacteroidetes and to a lesser degree by Actinobacteria and Proteobacteria, with each individual harbouring at least 160 such species. Gut microbiota contributes to blood pressure homeostasis and the pathogenesis of arterial hypertension through production, modification, and degradation of a variety of microbial-derived bioactive metabolites. Animal studies and to a lesser degree human research has unmasked relative mechanisms, mainly through the effect of certain microbiome metabolites and their receptors, outlining this relationship. Interventions to utilize these pathways, with probiotics, prebiotics, antibiotics and fecal microbiome transplantation have shown promising results. Personalized microbiome-based disease prediction and treatment responsiveness seem futuristic. Undoubtedly, a long way of experimental and clinical research should be pursued to elucidate this novel, intriguing and very promising horizon.}, }
@article {pmid29881381, year = {2018}, author = {Tsigalou, C and Stavropoulou, E and Bezirtzoglou, E}, title = {Current Insights in Microbiome Shifts in Sjogren's Syndrome and Possible Therapeutic Interventions.}, journal = {Frontiers in immunology}, volume = {9}, number = {}, pages = {1106}, pmid = {29881381}, issn = {1664-3224}, mesh = {Clinical Decision-Making ; Combined Modality Therapy ; Diet Therapy ; Disease Management ; Humans ; Microbiota/*immunology ; Probiotics ; Sjogren's Syndrome/etiology/metabolism/*therapy ; Treatment Outcome ; }, abstract = {Sjogren's syndrome (SS) is an autoimmune disease, among the most common ones, that targets mainly the exocrine glands as well as extra-glandular epithelial tissues. Their lymphocytic infiltration leads to manifestations from other organs (e.g., kidneys, lungs, liver, or thyroid), apart from sicca symptoms (xerostomia and keratoconjunctivitis). SS is more prevalent in women than in men (9:1). Moreover, p.SS patients are in increased risk to develop lymphoma. Certain autoantibodies (e.g., antibodies against ribonucleoprotein autoantigens Ro-SSA and La-SSB) are ultimate hallmarks for the disease. It was not known until recently that culture-independent techniques like next-generation sequencing (NGS) facilitate the study of the microbe communities in humans and scientists achieved to define the outlines of the microbiome contribution in health and disease. Researchers have started to investigate the alterations in diversity of the oral, ocular, or intestinal microbiota in SS. Recent studies indicate that dysbiosis may play a significant role in SS pathogenesis. At the same time, the cause or effect is not clear yet because the dysfunction of salivary glands induces alterations in oral and intestinal microbiome which is linked to worsen of symptoms and disease severity. If the human microbiome proves to play a key role in pathogenesis and manifestation of SS, the next step could be new and promising therapeutic approaches such as probiotics or prebiotics. This mini review focuses on the alterations of microbiome of SS patients, their connection with immune tolerance and new therapeutic strategies involving diet manipulation toward future personalized medicine.}, }
@article {pmid29878050, year = {2018}, author = {Albayrak, L and Khanipov, K and Golovko, G and Fofanov, Y}, title = {Detection of multi-dimensional co-exclusion patterns in microbial communities.}, journal = {Bioinformatics (Oxford, England)}, volume = {34}, number = {21}, pages = {3695-3701}, doi = {10.1093/bioinformatics/bty414}, pmid = {29878050}, issn = {1367-4811}, mesh = {Humans ; *Microbiota ; Software ; }, abstract = {MOTIVATION: Identification of complex relationships among members of microbial communities is key to understand and control the microbiota. Co-exclusion is arguably one of the most important patterns reflecting micro-organisms' intolerance to each other's presence. Knowing these relations opens an opportunity to manipulate microbiotas, personalize anti-microbial and probiotic treatments as well as guide microbiota transplantation. The co-exclusion pattern however, cannot be appropriately described by a linear function nor its strength be estimated using covariance or (negative) Pearson and Spearman correlation coefficients. This manuscript proposes a way to quantify the strength and evaluate the statistical significance of co-exclusion patterns between two, three or more variables describing a microbiota and allows one to extend analysis beyond micro-organism abundance by including other microbiome associated measurements such as, pH, temperature etc., as well as estimate the expected numbers of false positive co-exclusion patterns in a co-exclusion network.<br><br>RESULTS: The implemented computational pipeline (CoEx) tested against 2380 microbial profiles (samples) from The Human Microbiome Project resulted in body-site specific pairwise co-exclusion patterns.<br><br>C++&#x2009;source code for calculation of the score and P-value for two, three and four dimensional co-exclusion patterns as well as source code and executable files for the CoEx pipeline are available at https://scsb.utmb.edu/labgroups/fofanov/co-exclusion_in_microbial_communities.asp.<br><br>SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.}, }
@article {pmid29875143, year = {2018}, author = {Wandro, S and Osborne, S and Enriquez, C and Bixby, C and Arrieta, A and Whiteson, K}, title = {The Microbiome and Metabolome of Preterm Infant Stool Are Personalized and Not Driven by Health Outcomes, Including Necrotizing Enterocolitis and Late-Onset Sepsis.}, journal = {mSphere}, volume = {3}, number = {3}, pages = {}, pmid = {29875143}, issn = {2379-5042}, support = {U24 DK097154/DK/NIDDK NIH HHS/United States ; UL1 TR001414/TR/NCATS NIH HHS/United States ; }, mesh = {Cluster Analysis ; DNA, Bacterial/chemistry/genetics ; DNA, Ribosomal/chemistry/genetics ; Enterocolitis, Necrotizing/*microbiology ; Feces/*chemistry/*microbiology ; Gas Chromatography-Mass Spectrometry ; *Gastrointestinal Microbiome ; Humans ; Infant ; Infant, Newborn ; *Infant, Premature ; Infant, Very Low Birth Weight ; Late Onset Disorders ; *Metabolome ; Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sepsis/*microbiology ; Sequence Analysis, DNA ; }, abstract = {The assembly and development of the gut microbiome in infants have important consequences for immediate and long-term health. Preterm infants represent an abnormal case for bacterial colonization because of early exposure to bacteria and frequent use of antibiotics. To better understand the assembly of the gut microbiota in preterm infants, fecal samples were collected from 32 very low birth weight preterm infants over the first 6 weeks of life. Infant health outcomes included health, late-onset sepsis, and necrotizing enterocolitis (NEC). We characterized bacterial compositions by 16S rRNA gene sequencing and metabolomes by untargeted gas chromatography-mass spectrometry. Preterm infant fecal samples lacked beneficial Bifidobacterium spp. and were dominated by Enterobacteriaceae, Enterococcus, and Staphylococcus organisms due to nearly uniform antibiotic administration. Most of the variance between the microbial community compositions could be attributed to the baby from which the sample derived (permutational multivariate analysis of variance [PERMANOVA] R[2] = 0.48, P < 0.001), while clinical status (health, NEC, or late-onset sepsis) and overlapping times in the neonatal intensive care unit (NICU) did not explain a significant amount of variation in bacterial composition. Fecal metabolomes were also found to be unique to the individual (PERMANOVA R[2] = 0.43, P < 0.001) and weakly associated with bacterial composition (Mantel statistic r = 0.23 ± 0.05, P < 0.05). No measured metabolites were found to be associated with necrotizing enterocolitis, late-onset sepsis, or a healthy outcome. Overall, preterm infant gut microbial communities were personalized and reflected antibiotic usage.IMPORTANCE Preterm infants face health problems likely related to microbial exposures, including sepsis and necrotizing enterocolitis. However, the role of the gut microbiome in preterm infant health is poorly understood. Microbial colonization differs from that of healthy term babies because it occurs in the NICU and is often perturbed by antibiotics. We measured bacterial compositions and metabolomic profiles of 77 fecal samples from 32 preterm infants to investigate the differences between microbiomes in health and disease. Rather than finding microbial signatures of disease, we found that both the preterm infant microbiome and the metabolome were personalized and that the preterm infant gut microbiome is enriched in microbes that commonly dominate in the presence of antibiotics. These results contribute to the growing knowledge of the preterm infant microbiome and emphasize that a personalized view will be important to disentangle the health consequences of the preterm infant microbiome.}, }
@article {pmid29870114, year = {2018}, author = {Chin-Yee, B and Subramanian, SV and Verma, AA and Laupacis, A and Razak, F}, title = {Emerging Trends in Clinical Research: With Implications for Population Health and Health Policy.}, journal = {The Milbank quarterly}, volume = {96}, number = {2}, pages = {369-401}, pmid = {29870114}, issn = {1468-0009}, mesh = {Clinical Nursing Research/*trends ; Clinical Trials as Topic/*statistics &amp; numerical data ; Forecasting ; Health Equity/*trends ; Health Policy/*trends ; Humans ; Population Health/*statistics &amp; numerical data ; }, abstract = {UNLABELLED: Policy Points: Significant advances in clinical medicine that have broader societal relevance may be less accessible to population health researchers and policymakers because of increased specialization within fields. We describe important recent clinical advances and discuss their broader societal impact. These advances include more expansive strategies for disease prevention, the rise of precision medicine, applications of human microbiome research, and new and highly successful treatments for hepatitis C infection. These recent developments in clinical research raise important issues surrounding health care costs and equitable resource allocation that necessitate an ongoing dialogue among the fields of clinical medicine, population health, and health policy.<br><br>CONTEXT: Developments in clinical medicine have important implications for population health, and there is a need for interdisciplinary engagement among clinical medicine, the social sciences, and public health research. The aim of this article is to help bridge the divide between these fields by exploring major recent advances in clinical medicine that have important implications for population health.<br><br>METHODS: We reviewed the most cited articles published from 2010 to 2015 in 5 high-impact clinical journals and selected 5 randomized controlled trials and 2 related clinical practice guidelines that are broadly relevant to population health and policy.<br><br>FINDINGS: We discuss the following themes: (1) expanding indications for drug therapy and the inherent medicalization of the population as highlighted by studies and clinical guidelines supporting lower blood pressure targets or widespread statin use; (2) the tension in nutritional research between quantifying the impact of isolated nutrients and studying specific foods and dietary patterns, for example, the role of the Mediterranean diet in the primary prevention of cardiovascular disease; (3) the issue of high medication costs and the challenge of providing equitable access raised by the development of new and effective treatments for hepatitis C infection; (4) emerging clinical applications of research on the human microbiome as illustrated by fecal transplant to treat Clostridium difficile infections; and (5) the promise and limitations of precision medicine as demonstrated by the rise of novel targeted therapies in oncology.<br><br>CONCLUSIONS: These developments in clinical science hold promise for improving individual and population health and raise important questions about resource allocation, the role of prevention, and health disparities.}, }
@article {pmid29868846, year = {2019}, author = {Sankaran, K and Holmes, SP}, title = {Latent variable modeling for the microbiome.}, journal = {Biostatistics (Oxford, England)}, volume = {20}, number = {4}, pages = {599-614}, pmid = {29868846}, issn = {1468-4357}, support = {R01 AI112401/AI/NIAID NIH HHS/United States ; T32 GM096982/GM/NIGMS NIH HHS/United States ; }, mesh = {Biostatistics/*methods ; Humans ; *Microbiota ; *Models, Statistical ; }, abstract = {The human microbiome is a complex ecological system, and describing its structure and function under different environmental conditions is important from both basic scientific and medical perspectives. Viewed through a biostatistical lens, many microbiome analysis goals can be formulated as latent variable modeling problems. However, although probabilistic latent variable models are a cornerstone of modern unsupervised learning, they are rarely applied in the context of microbiome data analysis, in spite of the evolutionary, temporal, and count structure that could be directly incorporated through such models. We explore the application of probabilistic latent variable models to microbiome data, with a focus on Latent Dirichlet allocation, Non-negative matrix factorization, and Dynamic Unigram models. To develop guidelines for when different methods are appropriate, we perform a simulation study. We further illustrate and compare these techniques using the data of Dethlefsen and Relman (2011, Incomplete recovery and individualized responses of the human distal gut microbiota to repeated antibiotic perturbation. Proceedings of the National Academy of Sciences108, 4554-4561), a study on the effects of antibiotics on bacterial community composition. Code and data for all simulations and case studies are available publicly.}, }
@article {pmid29868514, year = {2018}, author = {Chai, Q and Zhang, Y and Liu, CH}, title = {Mycobacterium tuberculosis: An Adaptable Pathogen Associated With Multiple Human Diseases.}, journal = {Frontiers in cellular and infection microbiology}, volume = {8}, number = {}, pages = {158}, pmid = {29868514}, issn = {2235-2988}, mesh = {Autoimmune Diseases/complications ; Granuloma/immunology ; Host-Pathogen Interactions/*immunology ; Humans ; *Immune System ; Metabolic Syndrome/complications ; Microbial Interactions/immunology ; Microbiota ; Mycobacterium tuberculosis/*pathogenicity ; Recurrence ; Tuberculosis/complications/*immunology/microbiology ; Tuberculosis, Pulmonary/complications ; }, abstract = {Mycobacterium tuberculosis, the etiological agent of tuberculosis (TB), is an extremely successful pathogen that adapts to survive within the host. During the latency phase of infection, M. tuberculosis employs a range of effector proteins to be cloud the host immune system and shapes its lifestyle to reside in granulomas, sophisticated, and organized structures of immune cells that are established by the host in response to persistent infection. While normally being restrained in immunocompetent hosts, M. tuberculosis within granulomas can cause the recrudescence of TB when host immunity is compromised. Aside from causing TB, accumulating evidence suggests that M. tuberculosis is also associated with multiple other human diseases, such as pulmonary complications, autoimmune diseases, and metabolic syndromes. Furthermore, it has been recently appreciated that M. tuberculosis infection can also reciprocally interact with the human microbiome, which has a strong link to immune balance and health. In this review, we highlight the adaptive survival of M. tuberculosis within the host and provide an overview for regulatory mechanisms underlying interactions between M. tuberculosis infection and multiple important human diseases. A better understanding of how M. tuberculosis regulates the host immune system to cause TB and reciprocally regulates other human diseases is critical for developing rational treatments to better control TB and help alleviate its associated comorbidities.}, }
@article {pmid29844606, year = {2018}, author = {Reid, G}, title = {What are bacteria doing in the bladder?.}, journal = {Nature reviews. Urology}, volume = {15}, number = {8}, pages = {469-470}, doi = {10.1038/s41585-018-0032-y}, pmid = {29844606}, issn = {1759-4820}, mesh = {Bacteria ; Female ; Humans ; *Microbiota ; *Urinary Bladder ; Urogenital System ; }, }
@article {pmid29802603, year = {2018}, author = {Stefano, GB and Pilonis, N and Ptacek, R and Raboch, J and Vnukova, M and Kream, RM}, title = {Gut, Microbiome, and Brain Regulatory Axis: Relevance to Neurodegenerative and Psychiatric Disorders.}, journal = {Cellular and molecular neurobiology}, volume = {38}, number = {6}, pages = {1197-1206}, pmid = {29802603}, issn = {1573-6830}, mesh = {Animals ; Brain/*metabolism/physiopathology ; Dysbiosis/*genetics ; Gastrointestinal Microbiome/*genetics ; Humans ; Mental Disorders/genetics/physiopathology ; Microbiota/*genetics ; Parkinson Disease/*genetics/physiopathology ; }, abstract = {It has become apparent that the molecular and biochemical integrity of interactive families, genera, and species of human gut microflora is critically linked to maintaining complex metabolic and behavioral processes mediated by peripheral organ systems and central nervous system neuronal groupings. Relatively recent studies have established intrinsic ratios of enterotypes contained within the human microbiome across demographic subpopulations and have empirically linked significant alterations in the expression of bacterial enterotypes with the initiation and persistence of several major metabolic and psychiatric disorders. Accordingly, the goal of our review is to highlight potential thematic/functional linkages of pathophysiological alterations in gut microbiota and bidirectional gut-brain signaling pathways with special emphasis on the potential roles of gut dysbiosis on the pathophysiology of psychiatric illnesses. We provide critical discussion of putative thematic linkages of Parkinson's disease (PD) data sets to similar pathophysiological events as potential causative factors in the development and persistence of diverse psychiatric illnesses. Finally, we include a concise review of preclinical paradigms that involve immunologically-induced GI deficits and dysbiosis of maternal microflora that are functionally linked to impaired neurodevelopmental processes leading to affective behavioral syndromes in the offspring.}, }
@article {pmid29795809, year = {2018}, author = {McDonald, D and Hyde, E and Debelius, JW and Morton, JT and Gonzalez, A and Ackermann, G and Aksenov, AA and Behsaz, B and Brennan, C and Chen, Y and DeRight Goldasich, L and Dorrestein, PC and Dunn, RR and Fahimipour, AK and Gaffney, J and Gilbert, JA and Gogul, G and Green, JL and Hugenholtz, P and Humphrey, G and Huttenhower, C and Jackson, MA and Janssen, S and Jeste, DV and Jiang, L and Kelley, ST and Knights, D and Kosciolek, T and Ladau, J and Leach, J and Marotz, C and Meleshko, D and Melnik, AV and Metcalf, JL and Mohimani, H and Montassier, E and Navas-Molina, J and Nguyen, TT and Peddada, S and Pevzner, P and Pollard, KS and Rahnavard, G and Robbins-Pianka, A and Sangwan, N and Shorenstein, J and Smarr, L and Song, SJ and Spector, T and Swafford, AD and Thackray, VG and Thompson, LR and Tripathi, A and Vázquez-Baeza, Y and Vrbanac, A and Wischmeyer, P and Wolfe, E and Zhu, Q and ,  and Knight, R}, title = {American Gut: an Open Platform for Citizen Science Microbiome Research.}, journal = {mSystems}, volume = {3}, number = {3}, pages = {}, pmid = {29795809}, issn = {2379-5077}, support = {MR/N01183X/1/MRC_/Medical Research Council/United Kingdom ; P30 DK042086/DK/NIDDK NIH HHS/United States ; P30 DK043351/DK/NIDDK NIH HHS/United States ; MR/N030125/1/MRC_/Medical Research Council/United Kingdom ; T32 GM007752/GM/NIGMS NIH HHS/United States ; /WT_/Wellcome Trust/United Kingdom ; }, abstract = {Although much work has linked the human microbiome to specific phenotypes and lifestyle variables, data from different projects have been challenging to integrate and the extent of microbial and molecular diversity in human stool remains unknown. Using standardized protocols from the Earth Microbiome Project and sample contributions from over 10,000 citizen-scientists, together with an open research network, we compare human microbiome specimens primarily from the United States, United Kingdom, and Australia to one another and to environmental samples. Our results show an unexpected range of beta-diversity in human stool microbiomes compared to environmental samples; demonstrate the utility of procedures for removing the effects of overgrowth during room-temperature shipping for revealing phenotype correlations; uncover new molecules and kinds of molecular communities in the human stool metabolome; and examine emergent associations among the microbiome, metabolome, and the diversity of plants that are consumed (rather than relying on reductive categorical variables such as veganism, which have little or no explanatory power). We also demonstrate the utility of the living data resource and cross-cohort comparison to confirm existing associations between the microbiome and psychiatric illness and to reveal the extent of microbiome change within one individual during surgery, providing a paradigm for open microbiome research and education. IMPORTANCE We show that a citizen science, self-selected cohort shipping samples through the mail at room temperature recaptures many known microbiome results from clinically collected cohorts and reveals new ones. Of particular interest is integrating n = 1 study data with the population data, showing that the extent of microbiome change after events such as surgery can exceed differences between distinct environmental biomes, and the effect of diverse plants in the diet, which we confirm with untargeted metabolomics on hundreds of samples.}, }
@article {pmid29795140, year = {2018}, author = {Porter, CM and Shrestha, E and Peiffer, LB and Sfanos, KS}, title = {The microbiome in prostate inflammation and prostate cancer.}, journal = {Prostate cancer and prostatic diseases}, volume = {21}, number = {3}, pages = {345-354}, doi = {10.1038/s41391-018-0041-1}, pmid = {29795140}, issn = {1476-5608}, mesh = {Disease Progression ; Humans ; Male ; Microbiota/*physiology ; Prostate/*microbiology/pathology ; Prostatic Hyperplasia/immunology/*microbiology/pathology ; Prostatic Neoplasms/immunology/*microbiology/pathology ; Prostatitis/immunology/*microbiology/pathology ; Xenobiotics/immunology/metabolism ; }, abstract = {BACKGROUND: The human microbiome may influence prostate cancer initiation and/or progression through both direct and indirect interactions. To date, the majority of studies have focused on direct interactions including the influence of prostate infections on prostate cancer risk and, more recently, on the composition of the urinary microbiome in relation to prostate cancer. Less well understood are indirect interactions of the microbiome with prostate cancer, such as the influence of the gastrointestinal or oral microbiota on pro- or anti-carcinogenic xenobiotic metabolism, and treatment response.<br><br>METHODS: We review the literature to date on direct and indirect interactions of the microbiome with prostate inflammation and prostate cancer.<br><br>RESULTS: Emerging studies indicate that the microbiome can influence prostate inflammation in relation to benign prostate conditions such as prostatitis/chronic pelvic pain syndrome and benign prostatic hyperplasia, as well as in prostate cancer. We provide evidence that the human microbiome present at multiple anatomic sites (urinary tract, gastrointestinal tract, oral cavity, etc.) may play an important role in prostate health and disease.<br><br>CONCLUSIONS: In health, the microbiome encourages homeostasis and helps educate the immune system. In dysbiosis, a systemic inflammatory state may be induced, predisposing remote anatomical sites to disease, including cancer. The microbiome's ability to affect systemic hormone levels may also be important, particularly in a disease such as prostate cancer that is dually affected by estrogen and androgen levels. Due to the complexity of the potential interconnectedness between prostate cancer and the microbiome, it is vital to further explore and understand the relationships that are involved.}, }
@article {pmid29789680, year = {2018}, author = {Banerjee, S and Schlaeppi, K and van der Heijden, MGA}, title = {Keystone taxa as drivers of microbiome structure and functioning.}, journal = {Nature reviews. Microbiology}, volume = {16}, number = {9}, pages = {567-576}, doi = {10.1038/s41579-018-0024-1}, pmid = {29789680}, issn = {1740-1534}, mesh = {Animals ; Bacteria/classification/isolation &amp; purification/metabolism ; *Environmental Microbiology ; Humans ; *Microbiota ; }, abstract = {Microorganisms have a pivotal role in the functioning of ecosystems. Recent studies have shown that microbial communities harbour keystone taxa, which drive community composition and function irrespective of their abundance. In this Opinion article, we propose a definition of keystone taxa in microbial ecology and summarize over 200 microbial keystone taxa that have been identified in soil, plant and marine ecosystems, as well as in the human microbiome. We explore the importance of keystone taxa and keystone guilds for microbiome structure and functioning and discuss the factors that determine their distribution and activities.}, }
@article {pmid29786923, year = {2019}, author = {Bandara, HMHN and Panduwawala, CP and Samaranayake, LP}, title = {Biodiversity of the human oral mycobiome in health and disease.}, journal = {Oral diseases}, volume = {25}, number = {2}, pages = {363-371}, doi = {10.1111/odi.12899}, pmid = {29786923}, issn = {1601-0825}, mesh = {*Biodiversity ; Humans ; Immunocompromised Host ; Mouth/*microbiology/physiology ; Mouth Diseases/*microbiology ; *Mycobiome ; Mycological Typing Techniques ; Mycoses/*microbiology ; Saliva/microbiology ; }, abstract = {The organisms that colonize the human body over a lifetime are diverse, extensive and gargantuan. A fair proportion of the microbiota that constitutes this human microbiome live within our oral cavities mostly as harmonious associates causing only sporadic disease. An important core constituent of the microbiome is the mycobiome, representing various fungal genera. Up until recently, only a few species of fungi, mainly Candida species, were thought to constitute the human oral mycobiome. The reasons for this are manifold, although the uncultivable nature of many fungi in conventional laboratory media, and their complex genetic composition seem to be the major factors which eluded their detection over the years. Nevertheless, recent advances in computing and high-throughput sequencing such as next-generation sequencing (NGS) platforms have provided us a panoramic view of a totally new world of fungi that are human oral cohabitués. Their diversity is perplexing, and functionality yet to be deciphered. Here, we provide a glimpse of what is currently known of the oral mycobiome, in health and disease, with some future perspectives.}, }
@article {pmid29781826, year = {2018}, author = {Swami, U and Zakharia, Y and Zhang, J}, title = {Understanding Microbiome Effect on Immune Checkpoint Inhibition in Lung Cancer: Placing the Puzzle Pieces Together.}, journal = {Journal of immunotherapy (Hagerstown, Md. : 1997)}, volume = {41}, number = {8}, pages = {359-360}, doi = {10.1097/CJI.0000000000000232}, pmid = {29781826}, issn = {1537-4513}, mesh = {Animals ; B7-H1 Antigen/antagonists &amp; inhibitors ; CTLA-4 Antigen/antagonists &amp; inhibitors ; *Gastrointestinal Microbiome ; Humans ; *Immunotherapy ; *Lung Neoplasms/drug therapy/immunology/microbiology ; Programmed Cell Death 1 Receptor/antagonists &amp; inhibitors ; }, abstract = {Over the past couple of years, human microbiome has received increasing attention as a regulator and predictor of response to the therapies of various diseases. It is speculated that manipulating gut microbiome can modify response to cancer immunotherapies as well. Through this review, we have critically analyzed our current understanding of gut microbiome as a modulator of immunotherapies in lung cancer, explained conflicting data, evaluated current gaps and extrapolated our present knowledge to generate directions for future investigations.}, }
@article {pmid29773467, year = {2018}, author = {Daliri, EB and Tango, CN and Lee, BH and Oh, DH}, title = {Human microbiome restoration and safety.}, journal = {International journal of medical microbiology : IJMM}, volume = {308}, number = {5}, pages = {487-497}, doi = {10.1016/j.ijmm.2018.05.002}, pmid = {29773467}, issn = {1618-0607}, mesh = {Anti-Bacterial Agents ; Bacteria/classification/isolation &amp; purification ; Diet ; Dysbiosis/*therapy ; Fecal Microbiota Transplantation/*adverse effects/methods ; Gastrointestinal Microbiome/*physiology ; Humans ; Probiotics/*administration &amp; dosage ; }, abstract = {The human gut microbiome consists of many bacteria which are in symbiotic relationship with human beings. The gut microbial metabolism, as well as the microbial-host co-metabolism, has been found to greatly influence health and disease. Factors such as diet, antibiotic use and lifestyle have been associated with alterations in the gut microbial community and may result in several pathological conditions. For this reason, several strategies including fecal microbiota transplant and probiotic administration have been applied and proven to be feasible and effective in restoring the gut microbiota in humans. Yet, safety concerns such as potential health risks that may arise from such interventions and how these strategies are regulated need to be addressed. Also, it will be important to know if these microbiome restoration strategies can have a profound impact on health. This review provides an overview of our current knowledge of the microbiome restoration strategies and safety issues on how these strategies are regulated.}, }
@article {pmid29765359, year = {2018}, author = {Ingala, MR and Simmons, NB and Wultsch, C and Krampis, K and Speer, KA and Perkins, SL}, title = {Comparing Microbiome Sampling Methods in a Wild Mammal: Fecal and Intestinal Samples Record Different Signals of Host Ecology, Evolution.}, journal = {Frontiers in microbiology}, volume = {9}, number = {}, pages = {803}, pmid = {29765359}, issn = {1664-302X}, abstract = {The gut microbiome is a community of host-associated symbiotic microbes that fulfills multiple key roles in host metabolism, immune function, and tissue development. Given the ability of the microbiome to impact host fitness, there is increasing interest in studying the microbiome of wild animals to better understand these communities in the context of host ecology and evolution. Human microbiome research protocols are well established, but wildlife microbiome research is still a developing field. Currently, there is no standardized set of best practices guiding the collection of microbiome samples from wildlife. Gut microflora are typically sampled either by fecal collection, rectal swabbing, or by destructively sampling the intestinal contents of the host animal. Studies rarely include more than one sampling technique and no comparison of these methods currently exists for a wild mammal. Although some studies have hypothesized that the fecal microbiome is a nested subset of the intestinal microbiome, this hypothesis has not been formally tested. To address these issues, we examined guano (feces) and distal intestinal mucosa from 19 species of free-ranging bats from Lamanai, Belize, using 16S rRNA amplicon sequencing to compare microbial communities across sample types. We found that the diversity and composition of intestine and guano samples differed substantially. In addition, we conclude that signatures of host evolution are retained by studying gut microbiomes based on mucosal tissue samples, but not fecal samples. Conversely, fecal samples retained more signal of host diet than intestinal samples. These results suggest that fecal and intestinal sampling methods are not interchangeable, and that these two microbiotas record different information about the host from which they are isolated.}, }
@article {pmid29760467, year = {2018}, author = {Xian, P and Xuedong, Z and Xin, X and Yuqing, L and Yan, L and Jiyao, L and Xiaoquan, S and Shi, H and Jian, X and Ga, L}, title = {The Oral Microbiome Bank of China.}, journal = {International journal of oral science}, volume = {10}, number = {2}, pages = {16}, pmid = {29760467}, issn = {2049-3169}, mesh = {China ; Humans ; *Microbiota ; Mouth/*microbiology ; }, abstract = {The human microbiome project (HMP) promoted further understanding of human oral microbes. However, research on the human oral microbiota has not made as much progress as research on the gut microbiota. Currently, the causal relationship between the oral microbiota and oral diseases remains unclear, and little is known about the link between the oral microbiota and human systemic diseases. To further understand the contribution of the oral microbiota in oral diseases and systemic diseases, a Human Oral Microbiome Database (HOMD) was established in the US. The HOMD includes 619 taxa in 13 phyla, and most of the microorganisms are from American populations. Due to individual differences in the microbiome, the HOMD does not reflect the Chinese oral microbial status. Herein, we established a new oral microbiome database-the Oral Microbiome Bank of China (OMBC, http://www.sklod.org/ombc). Currently, the OMBC includes information on 289 bacterial strains and 720 clinical samples from the Chinese population, along with lab and clinical information. The OMBC is the first curated description of a Chinese-associated microbiome; it provides tools for use in investigating the role of the oral microbiome in health and diseases, and will give the community abundant data and strain information for future oral microbial studies.}, }
@article {pmid29756665, year = {2018}, author = {Watson, E and Reid, G}, title = {Metabolomics as a clinical testing method for the diagnosis of vaginal dysbiosis.}, journal = {American journal of reproductive immunology (New York, N.Y. : 1989)}, volume = {80}, number = {2}, pages = {e12979}, doi = {10.1111/aji.12979}, pmid = {29756665}, issn = {1600-0897}, mesh = {Dysbiosis/*microbiology ; Female ; Humans ; Metabolomics ; Microbiota/*physiology ; Vagina/*microbiology ; Vaginosis, Bacterial/diagnosis/*microbiology ; }, abstract = {Microbes play an important role in vaginal health, with lactobacilli a particularly abundant species. When dysbiosis occurs, the tools to determine whether it is a condition such as bacterial vaginosis, and whether it warrants antibiotic treatment, are currently suboptimal. We propose that standardization and implementation of an affordable metabolomics-based diagnostic technique could reduce instances of false positives, stress associated with misdiagnosis, and potentially save time and money. Basing diagnosis on the detection of pH elevated above 4.5 and specific polyamines could provide a better method to assist a physician determine whether treatment is warranted.}, }
@article {pmid29756604, year = {2018}, author = {Stefano, GB and Kream, RM}, title = {Alkaloids, Nitric Oxide, and Nitrite Reductases: Evolutionary Coupling as Key Regulators of Cellular Bioenergetics with Special Relevance to the Human Microbiome.}, journal = {Medical science monitor : international medical journal of experimental and clinical research}, volume = {24}, number = {}, pages = {3153-3158}, pmid = {29756604}, issn = {1643-3750}, mesh = {Alkaloids/*metabolism ; *Biological Evolution ; *Energy Metabolism ; Humans ; *Microbiota ; Nitric Oxide/*metabolism ; Nitrite Reductases/*metabolism ; }, abstract = {Typical alkaloids expressed by prokaryotic and eukaryotic cells are small heterocyclic compounds containing weakly basic nitrogen groups that are critically important for mediating essential biological activities. The prototype opiate alkaloid morphine represents a low molecular mass heterocyclic compound that has been evolutionarily fashioned from a relatively restricted role as a secreted antimicrobial phytoalexin into a broad spectrum regulatory molecule. As an essential corollary, positive evolutionary pressure has driven the development of a cognate 6-transmembrane helical (TMH) domain μ3 opiate receptor that is exclusively responsive to morphine and related opiate alkaloids. A key aspect of "morphinergic" signaling mediated by μ3 opiate receptor activation is its functional coupling with regulatory pathways utilizing constitutive nitric oxide (NO) as a signaling molecule. Importantly, tonic and phasic intra-mitochondrial NO production exerts profound inhibitory effects on the rate of electron transport, H+ pumping, and O2 consumption. Given the pluripotent role of NO as a selective, temporally-defined chemical regulator of mitochondrial respiration and cellular bioenergetics, the expansion of prokaryotic denitrification systems into mitochondrial NO/nitrite cycling complexes represents a series of evolutionary modifications of existential proportions. Presently, our short review provides selective discussion of evolutionary development of morphine, opiate alkaloids, μ3 opiate receptors, and NO systems, within the perspectives of enhanced mitochondrial function, cellular bioenergetics, and the human microbiome.}, }
@article {pmid29753695, year = {2018}, author = {Chu, DM and Seferovic, M and Pace, RM and Aagaard, KM}, title = {The microbiome in preterm birth.}, journal = {Best practice &amp; research. Clinical obstetrics &amp; gynaecology}, volume = {52}, number = {}, pages = {103-113}, doi = {10.1016/j.bpobgyn.2018.03.006}, pmid = {29753695}, issn = {1532-1932}, mesh = {Female ; Humans ; Lactobacillus/metabolism ; Longitudinal Studies ; *Microbiota ; Placenta/microbiology ; Pregnancy ; Premature Birth/*microbiology ; Vagina/microbiology ; }, abstract = {The microbiome is thought to play a role in the maintenance of a healthy pregnancy and thus may either contribute to or protect from preterm birth. Study of the human microbiome has been aided by metagenomic sequencing approaches, providing greater insight into the commensal bacteria that coexist in and on our bodies. The vaginal microbiome has been the most widely studied, though there have been recent efforts to explore the gut, cervical-vaginal, placental and oral microbiomes in the further search of etiologies of preterm birth. To date, a specific microbiome community or microorganism has yet to be reliably associated with preterm birth. This is partly due to the fact that the 'normal' constituents' microbiome can vary widely between healthy individuals. Before our knowledge of the microbiome can be utilized and applied in clinical practice, a greater understanding of the 'healthy' microbiome must be achieved. In particular, we must first appreciate how our microbes influence our biology to promote a healthy pregnancy or alternately render preterm birth.}, }
@article {pmid29747892, year = {2018}, author = {Valentine, G and Chu, DM and Stewart, CJ and Aagaard, KM}, title = {Relationships Between Perinatal Interventions, Maternal-Infant Microbiomes, and Neonatal Outcomes.}, journal = {Clinics in perinatology}, volume = {45}, number = {2}, pages = {339-355}, doi = {10.1016/j.clp.2018.01.008}, pmid = {29747892}, issn = {1557-9840}, mesh = {Adult ; Female ; Fetal Diseases/*microbiology ; Humans ; *Infant Health ; Infant, Newborn ; Infant, Newborn, Diseases/*microbiology/therapy ; Male ; *Maternal Health ; Microbiota/immunology/*physiology ; Perinatal Care/methods ; Pregnancy ; Premature Birth/*microbiology ; Prenatal Care/methods ; Probiotics/administration &amp; dosage ; }, abstract = {The human microbiome acquires its vastness and diversity over a relatively short time period during development. Much is unknown, however, about the precise prenatal versus postnatal timing or its sources and determinants. Given early evidence of a role for influences during pregnancy and early neonatal and infant life on the microbiome and subsequent metabolic health, research investigating the development and shaping of the microbiome in the fetus and neonate is an important arena for study. This article reviews the relevant available literature and future questions on what shapes the microbiome during early development and mechanisms for doing so.}, }
@article {pmid29743478, year = {2018}, author = {Olde Loohuis, LM and Mangul, S and Ori, APS and Jospin, G and Koslicki, D and Yang, HT and Wu, T and Boks, MP and Lomen-Hoerth, C and Wiedau-Pazos, M and Cantor, RM and de Vos, WM and Kahn, RS and Eskin, E and Ophoff, RA}, title = {Transcriptome analysis in whole blood reveals increased microbial diversity in schizophrenia.}, journal = {Translational psychiatry}, volume = {8}, number = {1}, pages = {96}, pmid = {29743478}, issn = {2158-3188}, support = {R01 ES021801/ES/NIEHS NIH HHS/United States ; R01 MH078075/MH/NIMH NIH HHS/United States ; R01 MH101782/MH/NIMH NIH HHS/United States ; T32 NS048004/NS/NINDS NIH HHS/United States ; K25 HL080079/HL/NHLBI NIH HHS/United States ; P01 HL028481/HL/NHLBI NIH HHS/United States ; U01 DA024417/DA/NIDA NIH HHS/United States ; R01 NS058980/NS/NINDS NIH HHS/United States ; R01 ES022282/ES/NIEHS NIH HHS/United States ; R21 MH098035/MH/NIMH NIH HHS/United States ; P01 HL030568/HL/NHLBI NIH HHS/United States ; R01 MH090553/MH/NIMH NIH HHS/United States ; R01 GM083198/GM/NIGMS NIH HHS/United States ; }, mesh = {Adult ; Amyotrophic Lateral Sclerosis/blood/microbiology ; Bipolar Disorder/blood/microbiology ; Female ; Gene Expression Profiling ; Humans ; Male ; *Microbiota ; Middle Aged ; Schizophrenia/*blood/*microbiology ; Sequence Analysis, RNA ; Young Adult ; }, abstract = {The role of the human microbiome in health and disease is increasingly appreciated. We studied the composition of microbial communities present in blood across 192 individuals, including healthy controls and patients with three disorders affecting the brain: schizophrenia, amyotrophic lateral sclerosis, and bipolar disorder. By using high-quality unmapped RNA sequencing reads as candidate microbial reads, we performed profiling of microbial transcripts detected in whole blood. We were able to detect a wide range of bacterial and archaeal phyla in blood. Interestingly, we observed an increased microbial diversity in schizophrenia patients compared to the three other groups. We replicated this finding in an independent schizophrenia case-control cohort. This increased diversity is inversely correlated with estimated cell abundance of a subpopulation of CD8[+] memory T cells in healthy controls, supporting a link between microbial products found in blood, immunity and schizophrenia.}, }
@article {pmid29743119, year = {2018}, author = {Zolfo, M and Asnicar, F and Manghi, P and Pasolli, E and Tett, A and Segata, N}, title = {Profiling microbial strains in urban environments using metagenomic sequencing data.}, journal = {Biology direct}, volume = {13}, number = {1}, pages = {9}, pmid = {29743119}, issn = {1745-6150}, mesh = {Acinetobacter/genetics ; Genome, Bacterial/genetics ; Humans ; Metagenome/*genetics ; Metagenomics/*methods ; Microbiota/genetics ; Phylogeny ; }, abstract = {BACKGROUND: The microbial communities populating human and natural environments have been extensively characterized with shotgun metagenomics, which provides an in-depth representation of the microbial diversity within a sample. Microbes thriving in urban environments may be crucially important for human health, but have received less attention than those of other environments. Ongoing efforts started to target urban microbiomes at a large scale, but the most recent computational methods to profile these metagenomes have never been applied in this context. It is thus currently unclear whether such methods, that have proven successful at distinguishing even closely related strains in human microbiomes, are also effective in urban settings for tasks such as cultivation-free pathogen detection and microbial surveillance. Here, we aimed at a) testing the currently available metagenomic profiling tools on urban metagenomics; b) characterizing the organisms in urban environment at the resolution of single strain and c) discussing the biological insights that can be inferred from such methods.<br><br>RESULTS: We applied three complementary methods on the 1614 metagenomes of the CAMDA 2017 challenge. With MetaMLST we identified 121 known sequence-types from 15 species of clinical relevance. For instance, we identified several Acinetobacter strains that were close to the nosocomial opportunistic pathogen A. nosocomialis. With StrainPhlAn, a generalized version of the MetaMLST approach, we inferred the phylogenetic structure of Pseudomonas stutzeri strains and suggested that the strain-level heterogeneity in environmental samples is higher than in the human microbiome. Finally, we also probed the functional potential of the different strains with PanPhlAn. We further showed that SNV-based and pangenome-based profiling provide complementary information that can be combined to investigate the evolutionary trajectories of microbes and to identify specific genetic determinants of virulence and antibiotic resistances within closely related strains.<br><br>CONCLUSION: We show that strain-level methods developed primarily for the analysis of human microbiomes can be effective for city-associated microbiomes. In fact, (opportunistic) pathogens can be tracked and monitored across many hundreds of urban metagenomes. However, while more effort is needed to profile strains of currently uncharacterized species, this work poses the basis for high-resolution analyses of microbiomes sampled in city and mass transportation environments.<br><br>REVIEWERS: This article was reviewed by Alexandra Bettina Graf, Daniel Huson and Trevor Cickovski.}, }
@article {pmid29739953, year = {2018}, author = {Ma, ZS}, title = {Diversity time-period and diversity-time-area relationships exemplified by the human microbiome.}, journal = {Scientific reports}, volume = {8}, number = {1}, pages = {7214}, pmid = {29739953}, issn = {2045-2322}, mesh = {Biodiversity ; Female ; Humans ; Microbiota/*genetics ; *Models, Statistical ; Time Factors ; Vagina/*microbiology ; }, abstract = {We extend the ecological laws of species-time relationship (STR) and species-time-area relationship (STAR) to general diversity time-period relationship (DTR) and diversity-time-area relationship (DTAR), and test the extensions with the human vaginal microbiome datasets by building 1460 DTR/DTAR models. Our extensions were inspired by the observation that Hill numbers, well regarded as the most appropriate measure of alpha-diversity and also particularly suitable for multiplicative beta-diversity partitioning, are actually in the units of effective species, and therefore, should be able to substitute for species in the STR and STAR. We found that the traditional power law (PL) model is only applicable for DTR at diversity order zero (i.e., species richness); at higher diversity orders (q = 1-4), the power law with exponent cutoff (PLEC) and power law with inverse exponent cutoff (PLIEC) are more appropriate. In particular, PLEC has an advantage over PLIEC in predicting maximal accumulation diversity (MAD) over time. In fact, with the DTR extensions, we can construct DTR and MAD profiles. To the best of our knowledge, this is the first comprehensive investigation of the DTR/DTAR in human microbiome. Methodologically, our DTR/DTAR profiles can characterize general diversity scaling beyond species richness, covering both alpha- and beta-diversity regimes across different diversity orders.}, }
@article {pmid29737047, year = {2018}, author = {Zhao, N and Zhan, X and Guthrie, KA and Mitchell, CM and Larson, J}, title = {Generalized Hotelling's test for paired compositional data with application to human microbiome studies.}, journal = {Genetic epidemiology}, volume = {42}, number = {5}, pages = {459-469}, doi = {10.1002/gepi.22127}, pmid = {29737047}, issn = {1098-2272}, mesh = {Computer Simulation ; Databases as Topic ; Female ; Humans ; *Microbiota ; *Models, Genetic ; Postmenopause ; Vagina/microbiology ; }, abstract = {The human microbiome is a dynamic system that changes due to diseases, medication, change in diet, etc. The paired design is a common approach to evaluate the microbial changes while controlling for the inherent differences between people. For example, microbiome data may be collected from the same individuals before and after a treatment. Two challenges exist in analyzing this type of data. First, microbiome data are compositional such that the reads for all taxa in each sample are constrained to sum to a constant. Second, the number of taxa can be much larger than the sample size. Few statistical methods exist to analyze such data besides methods that test one taxon at a time. In this paper, we propose to first conduct a log-ratio transformation of the compositions, and then develop a generalized Hotelling's test (GHT) to evaluate whether the average microbiome compositions are equivalent in the paired samples. We replace the sample covariance matrix in standard Hotelling's statistic by a shrinkage-based covariance, calculated as a weighted average of the sample covariance and a positive definite target matrix. The optimal weighting can be obtained for many commonly used target matrices. We develop a permutation procedure to assess the statistical significance. Extensive simulations show that our proposed method has well-controlled type I error and better power than a few ad hoc approaches. We apply our method to examine the vaginal microbiome changes in response to treatments for menopausal hot flashes. An R package " GHT" is freely available at https://github.com/zhaoni153/GHT.}, }
@article {pmid29728386, year = {2018}, author = {Feng, S and Bootsma, M and McLellan, SL}, title = {Human-Associated Lachnospiraceae Genetic Markers Improve Detection of Fecal Pollution Sources in Urban Waters.}, journal = {Applied and environmental microbiology}, volume = {84}, number = {14}, pages = {}, pmid = {29728386}, issn = {1098-5336}, support = {R01 AI091829/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Bacteroides/genetics/isolation &amp; purification ; Cats ; Cattle ; Charadriiformes ; Clostridiales/*genetics/*isolation &amp; purification ; DNA, Bacterial/genetics/*isolation &amp; purification ; Dogs ; Environmental Monitoring ; Feces/*microbiology ; Genes, Bacterial ; *Genetic Markers ; Humans ; RNA, Ribosomal, 16S/genetics/*isolation &amp; purification ; Real-Time Polymerase Chain Reaction ; Rivers/microbiology ; Sewage/microbiology ; Swine ; Water Microbiology ; Water Pollution ; }, abstract = {The human microbiome contains many organisms that could potentially be used as indicators of human fecal pollution. Here we report the development of two novel human-associated genetic marker assays that target organisms within the family Lachnospiraceae Next-generation sequencing of the V6 region of the 16S rRNA gene from sewage and animal stool samples identified 40 human-associated marker candidates with a robust signal in sewage and low or no occurrence in samples from nonhuman hosts. Two were chosen for quantitative PCR (qPCR) assay development using longer sequences (the V2 to V9 regions) generated from clone libraries. Validation of these assays with these markers, designated Lachno3 and Lachno12, was performed using fecal samples (n = 55) from cat, dog, pig, cow, deer, and gull sources, and the results were compared with those of established host-associated assays (the Lachno2 marker and two human Bacteroides markers, the HB and HF183/BacR287). Each of the established assays cross-reacted with samples from at least one other animal species, including animals common in urban areas. The Lachno3 and Lachno12 markers were primarily human associated; however, the Lachno12 marker demonstrated low levels of cross-reactivity with samples from select cows and nonspecific amplification with samples from pigs. This limitation may not be problematic when testing urban waters. These novel markers resolved ambiguous results from previous investigations of stormwater-impacted waters, demonstrating their utility. The complexity of the microbiome in humans and animals suggests that no single organism is strictly specific to humans, and the use of multiple complementary markers in combination will provide the highest resolution and specificity for assessing fecal pollution sources.IMPORTANCE Traditional fecal indicator bacteria do not distinguish animal from human fecal pollution, which is necessary to evaluate health risks and mitigate pollution sources. Assessing water in urban areas is challenging, since the water can be impacted by sewage, which has a high likelihood of carrying human pathogens, as well as pet and urban wildlife waste. We demonstrate that the Lachno3 and Lachno12 markers are human associated and highly specific for the detection of human fecal pollution from urban sources, offering reliable identification of fecal pollution sources in urban waters.}, }
@article {pmid29725592, year = {2018}, author = {Sigdel, TK and Mercer, N and Nandoe, S and Nicora, CD and Burnum-Johnson, K and Qian, WJ and Sarwal, MM}, title = {Urinary Virome Perturbations in Kidney Transplantation.}, journal = {Frontiers in medicine}, volume = {5}, number = {}, pages = {72}, pmid = {29725592}, issn = {2296-858X}, support = {DP3 DK110844/DK/NIDDK NIH HHS/United States ; P41 GM103493/GM/NIGMS NIH HHS/United States ; R01 DK083447/DK/NIDDK NIH HHS/United States ; }, abstract = {The human microbiome is important for health and plays a role in essential metabolic functions and protection from certain pathogens. Conversely, dysbiosis of the microbiome is seen in the context of various diseases. Recent studies have highlighted that a complex microbial community containing hundreds of bacteria colonizes the healthy urinary tract, but little is known about the human urinary viruses in health and disease. To evaluate the human urinary virome in the context of kidney transplantation (tx), variations in the composition of the urinary virome were evaluated in urine samples from normal healthy volunteers as well as patients with kidney disease after they had undergone kidney tx. Liquid chromatography-mass spectrometry/mass spectrometry analysis was undertaken on a selected cohort of 142 kidney tx patients and normal healthy controls, from a larger biobank of 770 kidney biopsy matched urine samples. In addition to analysis of normal healthy control urine, the cohort of kidney tx patients had biopsy confirmed phenotype classification, coincident with the urine sample analyzed, of stable grafts (STA), acute rejection, BK virus nephritis, and chronic allograft nephropathy. We identified 37 unique viruses, 29 of which are being identified for the first time in human urine samples. The composition of the human urinary virome differs in health and kidney injury, and the distribution of viral proteins in the urinary tract may be further impacted by IS exposure, diet and environmental, dietary, or cutaneous exposure to various insecticides and pesticides.}, }
@article {pmid29724017, year = {2018}, author = {Avershina, E and Angell, IL and Simpson, M and Storrø, O and Øien, T and Johnsen, R and Rudi, K}, title = {Low Maternal Microbiota Sharing across Gut, Breast Milk and Vagina, as Revealed by 16S rRNA Gene and Reduced Metagenomic Sequencing.}, journal = {Genes}, volume = {9}, number = {5}, pages = {}, pmid = {29724017}, issn = {2073-4425}, abstract = {The maternal microbiota plays an important role in infant gut colonization. In this work we have investigated which bacterial species are shared across the breast milk, vaginal and stool microbiotas of 109 women shortly before and after giving birth using 16S rRNA gene sequencing and a novel reduced metagenomic sequencing (RMS) approach in a subgroup of 16 women. All the species predicted by the 16S rRNA gene sequencing were also detected by RMS analysis and there was good correspondence between their relative abundances estimated by both approaches. Both approaches also demonstrate a low level of maternal microbiota sharing across the population and RMS analysis identified only two species common to most women and in all sample types (Bifidobacterium longum and Enterococcus faecalis). Breast milk was the only sample type that had significantly higher intra- than inter- individual similarity towards both vaginal and stool samples. We also searched our RMS dataset against an in silico generated reference database derived from bacterial isolates in the Human Microbiome Project. The use of this reference-based search enabled further separation of Bifidobacterium longum into Bifidobacterium longum ssp. longum and Bifidobacterium longum ssp. infantis. We also detected the Lactobacillus rhamnosus GG strain, which was used as a probiotic supplement by some women, demonstrating the potential of RMS approach for deeper taxonomic delineation and estimation.}, }
@article {pmid29721973, year = {2018}, author = {Rowan, S and Taylor, A}, title = {The Role of Microbiota in Retinal Disease.}, journal = {Advances in experimental medicine and biology}, volume = {1074}, number = {}, pages = {429-435}, doi = {10.1007/978-3-319-75402-4_53}, pmid = {29721973}, issn = {0065-2598}, mesh = {Animals ; Conjunctiva/microbiology ; Cornea/microbiology ; Diabetic Retinopathy/microbiology/prevention &amp; control ; Disease Models, Animal ; Gastrointestinal Microbiome/drug effects/physiology ; Germ-Free Life ; Glaucoma/microbiology ; Humans ; Macular Degeneration/microbiology ; Metformin/pharmacology ; Mice ; Microbiota/*physiology ; Mouth/microbiology ; Retinal Diseases/*microbiology ; Uveitis/microbiology ; }, abstract = {The ten years since the first publications on the human microbiome project have brought enormous attention and insight into the role of the human microbiome in health and disease. Connections between populations of microbiota and ocular disease are now being established, and increased accessibility to microbiome research and insights into other diseases is expected to yield enormous information in the coming years. With the characterization of the ocular microbiome, important insights have already been made regarding corneal and conjunctival tissues. Roles for non-ocular microbiomes in complex retinal diseases are now being evaluated. For example, the gut microbiome has been implicated in the pathogenesis of uveitis. This short review will summarize the few studies linking gut or oral microbiota to diabetic retinopathy (DR), glaucoma, and age-related macular degeneration (AMD). We will also conjecture where the most significant findings still remain to be elucidated. Finally, we will propose the gut-retina axis, related but distinct from the gut-brain axis.}, }
@article {pmid29719941, year = {2018}, author = {Kwan, SE and Shaughnessy, RJ and Hegarty, B and Haverinen-Shaughnessy, U and Peccia, J}, title = {The reestablishment of microbial communities after surface cleaning in schools.}, journal = {Journal of applied microbiology}, volume = {125}, number = {3}, pages = {897-906}, doi = {10.1111/jam.13898}, pmid = {29719941}, issn = {1365-2672}, mesh = {Colony Count, Microbial ; DNA, Bacterial/isolation &amp; purification ; DNA, Fungal/isolation &amp; purification ; *Environmental Microbiology ; Equipment and Supplies/*microbiology ; Humans ; Infection Control ; *Schools ; }, abstract = {AIMS: The goal of this study was to quantify the indoor microbiome dynamics of bacterial and fungal communities on school desk surfaces during a cleaning intervention.<br><br>METHODS AND RESULTS: Quantitative PCR and DNA sequenced-based approaches were employed to describe microbial community dynamics on ten desk surfaces, spread across three schools, located in the Northeast region of the United States. Six samples were taken from each desk, one precleaning, and five postcleaning at 30&#xa0;min, 1, 3, 7 and 21&#xa0;days. Cleaning of the desks physically removed c.&#xa0;50% of bacteria, fungi, and human cells and a full recovery of the surface microbial concentrations occurred within 2-5&#xa0;days. This recovery period is much shorter than the schools' once per semester cleaning schedule. The dominant source of bacteria and fungi on desks at all time points came from the human microbiome (skin, oral cavity, and gut). More than 50% fungi on desks were members of genera that contain known allergens.<br><br>CONCLUSIONS: Microbial communities on these school desks are primarily generated and maintained from the deposition of human-associated bacteria and fungi. Current school surface cleaning protocols and cycles may be ineffective at reducing student exposure to fungal allergens and microbes of human origin.<br><br>Multiple students often share desks in schools. Results on the removal and reestablishment of microbial communities on these surfaces are critical for setting cleaning schedules and practices that effectively interrupt exposure to surface-associated pathogens and allergens.}, }
@article {pmid29718276, year = {2018}, author = {Reen, FJ and McGlacken, GP and O'Gara, F}, title = {The expanding horizon of alkyl quinolone signalling and communication in polycellular interactomes.}, journal = {FEMS microbiology letters}, volume = {365}, number = {9}, pages = {}, doi = {10.1093/femsle/fny076}, pmid = {29718276}, issn = {1574-6968}, mesh = {Animals ; Cystic Fibrosis/*microbiology ; Host-Pathogen Interactions ; Humans ; Microbial Interactions ; Pseudomonas Infections/*microbiology ; Pseudomonas aeruginosa/genetics/*metabolism ; Quinolones/*metabolism ; Signal Transduction ; }, abstract = {Population dynamics within natural ecosystems is underpinned by microbial diversity and the heterogeneity of host-microbe and microbe-microbe interactions. Small molecule signals that intersperse between species have been shown to govern many virulence-related processes in established and emerging pathogens. Understanding the capacity of microbes to decode diverse languages and adapt to the presence of 'non-self' cells will provide an important new direction to the understanding of the 'polycellular' interactome. Alkyl quinolones (AQs) have been described in the ESKAPE pathogen Pseudomonas aeruginosa, the primary agent associated with mortality in patients with cystic fibrosis and the third most prevalent nosocomial pathogen worldwide. The role of these molecules in governing the physiology and virulence of P. aeruginosa and other pathogens has received considerable attention, while a role in interspecies and interkingdom communication has recently emerged. Herein we discuss recent advances in our understanding of AQ signalling and communication in the context of microbe-microbe and microbe-host interactions. The integrated knowledge from these systems-based investigations will facilitate the development of new therapeutics based on the AQ framework that serves to disarm the pathogenesis of P. aeruginosa and competing pathogens.}, }
@article {pmid29715493, year = {2018}, author = {Rosado, MM and Aranburu, A and Scarsella, M and Cascioli, S and Giorda, E and Del Chierico, F and Mortera, SL and Mortari, EP and Petrini, S and Putignani, L and Carsetti, R}, title = {Spleen development is modulated by neonatal gut microbiota.}, journal = {Immunology letters}, volume = {199}, number = {}, pages = {1-15}, doi = {10.1016/j.imlet.2018.04.010}, pmid = {29715493}, issn = {1879-0542}, mesh = {Animals ; B-Lymphocytes/*immunology ; DNA-Binding Proteins/genetics ; Female ; Gastrointestinal Microbiome/*immunology ; Immunoglobulin A, Secretory/*immunology ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Mutant Strains ; Spleen/*growth &amp; development/*immunology ; T-Lymphocytes/immunology ; }, abstract = {The full development of the mammalian immune system occurs after birth upon exposure to non self-antigens. The gut is the first site of bacterial colonization where it is crucial to create the appropriate microenvironment able to balance effector or tolerogenic responses to external stimuli. It is a well-established fact that at mucosal sites bacteria play a key role in developing the immune system but we ignore how colonising bacteria impact the maturation of the spleen. Here we addressed this issue. Taking advantage of the fact that milk SIgA regulates bacterial colonization of the newborn intestine, we generated immunocompetent mice born either from IgA pro-efficient or IgA deficient females. Having demonstrated that SIgA in maternal milk modulates neonatal gut microbiota by promoting an increased diversity of the colonizing species we also found that immunocompetent pups, not exposed to milk SIgA, fail to properly develop the FDC network and primary follicles in the spleen compromising the response to T-dependent antigens. The presence of a less diverse microbiota with a higher representation of pathogenic species leads to a fast replenishment of the marginal zone and the IgM plasma cell compartment of the spleen as well as IgA plasma cells in the gut.}, }
@article {pmid29710488, year = {2018}, author = {Zhang, Y and Wang, X and Li, H and Ni, C and Du, Z and Yan, F}, title = {Human oral microbiota and its modulation for oral health.}, journal = {Biomedicine &amp; pharmacotherapy = Biomedecine &amp; pharmacotherapie}, volume = {99}, number = {}, pages = {883-893}, doi = {10.1016/j.biopha.2018.01.146}, pmid = {29710488}, issn = {1950-6007}, mesh = {Dental Caries/microbiology ; Humans ; *Microbiota ; Mouth/*microbiology ; Mouth Diseases/*microbiology ; Oral Health ; Periodontal Diseases/microbiology ; }, abstract = {The oral microbiome is an important part of the human microbiome. The oral cavity contains several significantly different niches with distinct microbial communities. A wide range of microorganisms inhabit the human oral cavity, including bacteria, fungi, viruses, archaea and protozoa. These microorganisms form a complex ecological community that influences oral and systemic health. The most prevalent oral diseases, dental caries and periodontal diseases, are microbiota-associated diseases. Moreover, increasing evidences have supported that many systemic diseases are associated with disturbances in the oral ecosystem, such as diabetes, cardiovascular diseases and tumors. The current control of dental plaque-related diseases is nonspecific and is centered on the removal of plaque by mechanical means. Due to this realization about the oral microbiome, several new methods based on the modulation of the microbiome that aim at maintaining and reestablishing a healthy oral ecosystem have been developed.}, }
@article {pmid29704918, year = {2018}, author = {Wilkinson, EM and Ilhan, ZE and Herbst-Kralovetz, MM}, title = {Microbiota-drug interactions: Impact on metabolism and efficacy of therapeutics.}, journal = {Maturitas}, volume = {112}, number = {}, pages = {53-63}, doi = {10.1016/j.maturitas.2018.03.012}, pmid = {29704918}, issn = {1873-4111}, mesh = {Animals ; Anti-Infective Agents/pharmacokinetics ; Anti-Inflammatory Agents/pharmacokinetics ; Antineoplastic Agents/pharmacokinetics ; Biotransformation ; *Drug Therapy ; Drug-Related Side Effects and Adverse Reactions/*metabolism ; Female ; Gastrointestinal Microbiome ; Humans ; Immunologic Factors/pharmacokinetics ; *Microbiota ; Vagina/microbiology ; }, abstract = {The microbiome not only represents a vital modifier of health and disease, but is a clinically important drug target. Therefore, study of the impact of the human microbiome on drug metabolism, toxicity and efficacy is urgently needed. This review focuses on gut and vaginal microbiomes, and the effect of those microbiomes or components thereof on the pharmacokinetics of specific chemotherapeutic agents, immunotherapies, anti-inflammatory and antimicrobial drugs. In some cases, the presence of specific bacterial species within the microbiome can alter the metabolism of certain drugs, such as chemotherapeutic agents and antiviral drugs. These microbiota-drug interactions are identified mostly through studies using germ-free or microbiome-depleted animal models, or by the administration of specific bacterial isolates. The biotransformation of drugs can cause drug-related toxicities; however, biotransformation also provides a mechanism by which drug developers could exploit host microbiota to create more site-specific drugs. Within this review we consider the importance of the route of drug administration and interactions with microbiota at various mucosal sites. Notably, we discuss the potential utility of bacterial therapeutics in altering the microbiome to enhance therapeutic efficacy and clinical outcomes in a personalized fashion. Based on the data to date, there is a clinically important relationship between microbiota and drug metabolism throughout the lifespan; therefore, profiling of the human microbiome will be essential in order to understand the mechanisms by which these microbiota-drug interactions occur and the degree to which this complex interplay affects drug efficacy.}, }
@article {pmid29693574, year = {2018}, author = {Del Chierico, F and Cardile, S and Pietrobattista, A and Liccardo, D and Russo, A and Candusso, M and Basso, MS and Grimaldi, C and Pansani, L and Bernaschi, P and Torre, G and Putignani, L}, title = {Liver Transplantation and Gut Microbiota Profiling in a Child Colonized by a Multi-Drug Resistant Klebsiella pneumoniae: A New Approach to Move from Antibiotic to "Eubiotic" Control of Microbial Resistance.}, journal = {International journal of molecular sciences}, volume = {19}, number = {5}, pages = {}, pmid = {29693574}, issn = {1422-0067}, mesh = {Anti-Bacterial Agents/pharmacology/therapeutic use ; Carbapenems/pharmacology/therapeutic use ; *Drug Resistance, Bacterial ; Female ; *Gastrointestinal Microbiome ; Humans ; Infant ; Klebsiella Infections/diagnosis/drug therapy/*microbiology ; Klebsiella pneumoniae/*drug effects/genetics/pathogenicity ; Liver Transplantation/*adverse effects ; Postoperative Complications/*diagnosis/drug therapy/*microbiology ; }, abstract = {The increase of microorganisms multi-drug resistant (MDR) to antibiotics (ATBs) is becoming a global emergency, especially in frail subjects. In chronic liver disease (LD) with indications for liver transplantation (LT), MDR colonization can significantly affect the LT outcome. However, no clear guidelines for microbial management are available. A novel approach toward MDR-colonized patients undergoing LT was developed at our Center refraining from ATBs use during the transplant waiting list, and use of an intensive perioperative prophylaxis cycle. This study aimed to couple clinical evaluation with monitoring of gut microbiota in a pediatric LD patient colonized with MDR Klebsiella pneumoniae (KP) who underwent LT. No peri-transplant complications were reported, and a decontamination from the MDR bacteria occurred during follow-up. Significant changes in gut microbiota, especially during ATB treatment, were reported by microbiota profiling. Patterns of Klebsiella predominance and microbiota diversity revealed opposite temporal trends, with Klebsiella ecological microbiota niches linked to ATB-driven selection. Our infection control program appeared to control complications following LT in an MDR-KP-colonized patient. The perioperative ATB regimen, acting as LT prophylaxis, triggered MDR-KP overgrowth and gut dysbiosis, but buffered infectious processes. Mechanisms modulating the gut ecosystem should be taken into account in MDR colonization clinical management.}, }
@article {pmid29692798, year = {2018}, author = {Roche-Lima, A and Carrasquillo-Carrión, K and Gómez-Moreno, R and Cruz, JM and Velázquez-Morales, DM and Rogozin, IB and Baerga-Ortiz, A}, title = {The Presence of Genotoxic and/or Pro-inflammatory Bacterial Genes in Gut Metagenomic Databases and Their Possible Link With Inflammatory Bowel Diseases.}, journal = {Frontiers in genetics}, volume = {9}, number = {}, pages = {116}, pmid = {29692798}, issn = {1664-8021}, support = {U54 MD007600/MD/NIMHD NIH HHS/United States ; R25 GM061838/GM/NIGMS NIH HHS/United States ; G12 RR003051/RR/NCRR NIH HHS/United States ; G12 MD007600/MD/NIMHD NIH HHS/United States ; R21 CA198963/CA/NCI NIH HHS/United States ; }, abstract = {Background: The human gut microbiota is a dynamic community of microorganisms that mediate important biochemical processes. Differences in the gut microbial composition have been associated with inflammatory bowel diseases (IBD) and other intestinal disorders. In this study, we quantified and compared the frequencies of eight genotoxic and/or pro-inflammatory bacterial genes found in metagenomic Whole Genome Sequences (mWGSs) of samples from individuals with IBD vs. a cohort of healthy human subjects. Methods: The eight selected gene sequences were clbN, clbB, cif, cnf-1, usp, tcpC from Escherichia coli, gelE from Enterococcus faecalis and murB from Akkermansia muciniphila. We also included the sequences for the conserved murB genes from E. coli and E. faecalis as markers for the presence of Enterobacteriaceae or Enterococci in the samples. The gene sequences were chosen based on their previously reported ability to disrupt normal cellular processes to either promote inflammation or to cause DNA damage in cultured cells or animal models, which could be linked to a role in IBD. The selected sequences were searched in three different mWGS datasets accessed through the Human Microbiome Project (HMP): a healthy cohort (N = 251), a Crohn's disease cohort (N = 60) and an ulcerative colitis cohort (N = 17). Results: Firstly, the sequences for the murB housekeeping genes from Enterobacteriaceae and Enterococci were more frequently found in the IBD cohorts (32% E. coli in IBD vs. 12% in healthy; 13% E. faecalis in IBD vs. 3% in healthy) than in the healthy cohort, confirming earlier reports of a higher presence of both of these taxa in IBD. For some of the sequences in our study, especially usp and gelE, their frequency was even more sharply increased in the IBD cohorts than in the healthy cohort, suggesting an association with IBD that is not easily explained by the increased presence of E. coli or E. faecalis in those samples. Conclusion: Our results suggest a significant association between the presence of some of these genotoxic or pro-inflammatory gene sequences and IBDs. In addition, these results illustrate the power and limitations of the HMP database in the detection of possible clinical correlations for individual bacterial genes.}, }
@article {pmid29686658, year = {2018}, author = {Quagliariello, A and Del Chierico, F and Russo, A and Reddel, S and Conte, G and Lopetuso, LR and Ianiro, G and Dallapiccola, B and Cardona, F and Gasbarrini, A and Putignani, L}, title = {Gut Microbiota Profiling and Gut-Brain Crosstalk in Children Affected by Pediatric Acute-Onset Neuropsychiatric Syndrome and Pediatric Autoimmune Neuropsychiatric Disorders Associated With Streptococcal Infections.}, journal = {Frontiers in microbiology}, volume = {9}, number = {}, pages = {675}, pmid = {29686658}, issn = {1664-302X}, abstract = {Pediatric acute-onset neuropsychiatric syndrome (PANS) and pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections syndrome (PANDAS) are conditions that impair brain normal neurologic function, resulting in the sudden onset of tics, obsessive-compulsive disorder, and other behavioral symptoms. Recent studies have emphasized the crosstalk between gut and brain, highlighting how gut composition can influence behavior and brain functions. Thus, the present study investigates the relationship between PANS/PANDAS and gut microbiota ecology. The gut composition of a cohort of 30 patients with PANS/PANDAS was analyzed and compared to control subjects using 16S rRNA-based metagenomics. Data were analyzed for their α- and β-diversity; differences in bacterial distribution were detected by Wilcoxon and LEfSe tests, while metabolic profile was predicted via PICRUSt software. These analyses demonstrate the presence of an altered bacterial community structure in PANS/PANDAS patients with respect to controls. In particular, ecological analysis revealed the presence of two main clusters of subjects based on age range. Thus, to avoid age bias, data from patients and controls were split into two groups: 4-8 years old and >9 years old. The younger PANS/PANDAS group was characterized by a strong increase in Bacteroidetes; in particular, Bacteroides, Odoribacter, and Oscillospira were identified as potential microbial biomarkers of this composition type. Moreover, this group exhibited an increase of several pathways concerning the modulation of the antibody response to inflammation within the gut as well as a decrease in pathways involved in brain function (i.e., SCFA, D-alanine and tyrosine metabolism, and the dopamine pathway). The older group of patients displayed a less uniform bacterial profile, thus impairing the identification of distinct biomarkers. Finally, Pearson's analysis between bacteria and anti-streptolysin O titer reveled a negative correlation between genera belonging to Firmicutes phylum and anti-streptolysin O while a positive correlation was observed with Odoribacter. In conclusion, this study suggests that streptococcal infections alter gut bacterial communities leading to a pro-inflammatory status through the selection of specific bacterial strains associated with gut inflammation and immune response activation. These findings highlight the possibility of studying bacterial biomarkers associated with this disorder and might led to novel potential therapeutic strategies.}, }
@article {pmid29685174, year = {2018}, author = {Fan, X and Peters, BA and Jacobs, EJ and Gapstur, SM and Purdue, MP and Freedman, ND and Alekseyenko, AV and Wu, J and Yang, L and Pei, Z and Hayes, RB and Ahn, J}, title = {Drinking alcohol is associated with variation in the human oral microbiome in a large study of American adults.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {59}, pmid = {29685174}, issn = {2049-2618}, support = {R01 CA159036/CA/NCI NIH HHS/United States ; P30 CA016087/CA/NCI NIH HHS/United States ; R01CA159036/CA/NCI NIH HHS/United States ; U01CA182370/CA/NCI NIH HHS/United States ; P30CA016087/CA/NCI NIH HHS/United States ; R21CA183887/CA/NCI NIH HHS/United States ; R21 CA183887/CA/NCI NIH HHS/United States ; R03 CA159414/CA/NCI NIH HHS/United States ; U01 CA182370/CA/NCI NIH HHS/United States ; R01CA164964/CA/NCI NIH HHS/United States ; R01 CA164964/CA/NCI NIH HHS/United States ; R03CA159414/CA/NCI NIH HHS/United States ; Pancreas Cancer Action Network Career Development Award//American Association for Cancer Research/International ; }, mesh = {Adult ; Aged ; Aged, 80 and over ; *Alcohol Drinking ; Female ; Humans ; Male ; Metagenome ; Metagenomics ; *Microbiota ; Middle Aged ; Mouth/*microbiology ; Public Health Surveillance ; RNA, Ribosomal, 16S/genetics ; United States ; }, abstract = {BACKGROUND: Dysbiosis of the oral microbiome can lead to local oral disease and potentially to cancers of the head, neck, and digestive tract. However, little is known regarding exogenous factors contributing to such microbial imbalance.<br><br>RESULTS: We examined the impact of alcohol consumption on the oral microbiome in a cross-sectional study of 1044 US adults. Bacterial 16S rRNA genes from oral wash samples were amplified, sequenced, and assigned to bacterial taxa. We tested the association of alcohol drinking level (non-drinker, moderate drinker, or heavy drinker) and type (liquor, beer, or wine) with overall microbial composition and individual taxon abundance. The diversity of oral microbiota and overall bacterial profiles differed between heavy drinkers and non-drinkers (&#x3b1;-diversity richness p&#xa0;=&#x2009;0.0059 and &#x3b2;-diversity unweighted UniFrac p&#xa0;=&#x2009;0.0036), and abundance of commensal order Lactobacillales tends to be decreased with higher alcohol consumption (fold changes&#x2009;=&#x2009;0.89 and 0.94 for heavy and moderate drinkers, p trend&#x2009;=&#x2009;0.005 [q&#xa0;=&#x2009;0.064]). Additionally, certain genera were enriched in subjects with higher alcohol consumption, including Actinomyces, Leptotrichia, Cardiobacterium, and Neisseria; some of these genera contain oral pathogens, while Neisseria can synthesize the human carcinogen acetaldehyde from ethanol. Wine drinkers may differ from non-drinkers in microbial diversity and profiles (&#x3b1;-diversity richness p&#xa0;=&#x2009;0.048 and &#x3b2;-diversity unweighted UniFrac p&#xa0;=&#x2009;0.059) after controlling for drinking amount, while liquor and beer drinkers did not. All significant differences between drinkers and non-drinkers remained after exclusion of current smokers.<br><br>CONCLUSIONS: Our results, from a large human study of alcohol consumption and the oral microbiome, indicate that alcohol consumption, and heavy drinking in particular, may influence the oral microbiome composition. These findings may have implications for better understanding the potential role that oral bacteria play in alcohol-related diseases.}, }
@article {pmid29682676, year = {2018}, author = {Cong, J and Zhang, X}, title = {How human microbiome talks to health and disease.}, journal = {European journal of clinical microbiology &amp; infectious diseases : official publication of the European Society of Clinical Microbiology}, volume = {37}, number = {9}, pages = {1595-1601}, pmid = {29682676}, issn = {1435-4373}, support = {2016M602094//China Postdoctoral Science Foundation/ ; 2016047//Qingdao Application Research Project/ ; 16-6-2-3-nsh//Qingdao People's Livelihood Science and Technology Program/ ; }, mesh = {Biomarkers ; Computational Biology ; Disease/*etiology ; Gastrointestinal Microbiome/genetics ; *Health ; Humans ; Microbiota/*genetics ; Mouth/microbiology ; Neoplasms/*therapy ; Skin/microbiology ; }, abstract = {Microbes are ubiquitous in the human body. They usually live in communities, and each of these communities has a distinct taxonomical structure. Due to its close relationship with human health and disease, the human microbiome has received great attention and is probably considered to be the most valuable biomarker in preventing and solving human diseases. In this paper, we first review the value of the human microbiome. Then, we focus on the role of the human microbiome in influencing human health and disease. Furthermore, we intensively discuss the relationship between intestinal microbiota and cancer therapy. Finally, we briefly summarize the significance of the human microbiome based on the development of sequencing and bioinformatic techniques.}, }
@article {pmid29675808, year = {2018}, author = {Ma, Y and Chen, H and Lan, C and Ren, J}, title = {Help, hope and hype: ethical considerations of human microbiome research and applications.}, journal = {Protein &amp; cell}, volume = {9}, number = {5}, pages = {404-415}, pmid = {29675808}, issn = {1674-8018}, mesh = {Biomedical Research/*ethics ; Humans ; *Microbiota ; Research Design/*standards ; }, }
@article {pmid29673211, year = {2018}, author = {Harsch, IA and Konturek, PC}, title = {The Role of Gut Microbiota in Obesity and Type 2 and Type 1 Diabetes Mellitus: New Insights into "Old" Diseases.}, journal = {Medical sciences (Basel, Switzerland)}, volume = {6}, number = {2}, pages = {}, pmid = {29673211}, issn = {2076-3271}, abstract = {The investigation of the human microbiome is the most rapidly expanding field in biomedicine. Early studies were undertaken to better understand the role of microbiota in carbohydrate digestion and utilization. These processes include polysaccharide degradation, glycan transport, glycolysis, and short-chain fatty acid production. Recent research has demonstrated that the intricate axis between gut microbiota and the host metabolism is much more complex. Gut microbiota&amp;mdash;depending on their composition&amp;mdash;have disease-promoting effects but can also possess protective properties. This review focuses on disorders of metabolic syndrome, with special regard to obesity as a prequel to type 2 diabetes, type 2 diabetes itself, and type 1 diabetes. In all these conditions, differences in the composition of the gut microbiota in comparison to healthy people have been reported. Mechanisms of the interaction between microbiota and host that have been characterized thus far include an increase in energy harvest, modulation of free fatty acids&amp;mdash;especially butyrate&amp;mdash;of bile acids, lipopolysaccharides, gamma-aminobutyric acid (GABA), an impact on toll-like receptors, the endocannabinoid system and &amp;ldquo;metabolic endotoxinemia&amp;rdquo; as well as &amp;ldquo;metabolic infection.&amp;rdquo; This review will also address the influence of already established therapies for metabolic syndrome and diabetes on the microbiota and the present state of attempts to alter the gut microbiota as a therapeutic strategy.}, }
@article {pmid29672703, year = {2018}, author = {Keshri, V and Panda, A and Levasseur, A and Rolain, JM and Pontarotti, P and Raoult, D}, title = {Phylogenomic Analysis of β-Lactamase in Archaea and Bacteria Enables the Identification of Putative New Members.}, journal = {Genome biology and evolution}, volume = {10}, number = {4}, pages = {1106-1114}, pmid = {29672703}, issn = {1759-6653}, mesh = {Anti-Bacterial Agents/adverse effects/therapeutic use ; Archaea/enzymology ; Bacteria/enzymology ; Carbapenems/*biosynthesis/chemistry ; Humans ; Metagenomics ; *Phylogeny ; beta-Lactamases/*genetics ; beta-Lactams/*metabolism ; }, abstract = {β-lactamases are enzymes which are commonly produced by bacteria and which degrade the β-lactam ring of β-lactam antibiotics, namely penicillins, cephalosporins, carbapenems, and monobactams, and inactivate these antibiotics. We performed a rational and comprehensive investigation of β-lactamases in different biological databases. In this study, we constructed hidden Markov model profiles as well as the ancestral sequence of four classes of β-lactamases (A, B, C, and D), which were used to identify potential β-lactamases from environmental metagenomic (1206), human microbiome metagenomic (6417), human microbiome reference genome (1310), and NCBI's nonredundant databases (44101). Our analysis revealed the existence of putative β-lactamases in the metagenomic databases, which appeared to be similar to the four different molecular classes (A-D). This is the first report on the large-scale phylogenetic diversity of new members of β-lactamases, and our results revealed that metagenomic database dark-matter contains β-lactamase-like antibiotic resistance genes.}, }
@article {pmid29669589, year = {2018}, author = {Coelho, LP and Kultima, JR and Costea, PI and Fournier, C and Pan, Y and Czarnecki-Maulden, G and Hayward, MR and Forslund, SK and Schmidt, TSB and Descombes, P and Jackson, JR and Li, Q and Bork, P}, title = {Similarity of the dog and human gut microbiomes in gene content and response to diet.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {72}, pmid = {29669589}, issn = {2049-2618}, support = {686070//Horizon 2020 Framework Programme (BE)/International ; }, mesh = {Animals ; *Diet ; Dogs ; Feces/microbiology ; *Gastrointestinal Microbiome ; Humans ; *Metagenome ; *Metagenomics/methods ; Mice ; *Microbiota ; Obesity ; Swine ; }, abstract = {BACKGROUND: Gut microbes influence their hosts in many ways, in particular by modulating the impact of diet. These effects have been studied most extensively in humans and mice. In this work, we used whole genome metagenomics to investigate the relationship between the gut metagenomes of dogs, humans, mice, and pigs.<br><br>RESULTS: We present a dog gut microbiome gene catalog containing 1,247,405 genes (based on 129 metagenomes and a total of 1.9 terabasepairs of sequencing data). Based on this catalog and taxonomic abundance profiling, we show that the dog microbiome is closer to the human microbiome than the microbiome of either pigs or mice. To investigate this similarity in terms of response to dietary changes, we report on a randomized intervention with two diets (high-protein/low-carbohydrate vs. lower protein/higher carbohydrate). We show that diet has a large and reproducible effect on the dog microbiome, independent of breed or sex. Moreover, the responses were in agreement with those observed in previous human studies.<br><br>CONCLUSIONS: We conclude that findings in dogs may be predictive of human microbiome results. In particular, a novel finding is that overweight or obese dogs experience larger compositional shifts than lean dogs in response to a high-protein diet.}, }
@article {pmid29668831, year = {2018}, author = {Maziarz, M and Pfeiffer, RM and Wan, Y and Gail, MH}, title = {Using standard microbiome reference groups to simplify beta-diversity analyses and facilitate independent validation.}, journal = {Bioinformatics (Oxford, England)}, volume = {34}, number = {19}, pages = {3249-3257}, pmid = {29668831}, issn = {1367-4811}, mesh = {*Computational Biology ; Feces/microbiology ; Humans ; *Microbiota ; Nose/microbiology ; }, abstract = {MOTIVATION: Comparisons of microbiome communities across populations are often based on pairwise distance measures (beta-diversity). Standard analyses (principal coordinate plots, permutation tests, kernel methods) require access to primary data if another investigator wants to add or compare independent data. We propose using standard reference measurements to simplify microbiome beta-diversity analyses, to make them more transparent, and to facilitate independent validation and comparisons across studies.<br><br>RESULTS: Using stool and nasal reference sets from the Human Microbiome Project (HMP), we computed mean distances (actually Bray-Curtis or Pearson correlation dissimilarities) to each reference set for each new sample. Thus, each new sample has two mean distances that can be plotted and analyzed with classical statistical methods. To test the approach, we studied independent (not reference) HMP subjects. Simple Hotelling tests demonstrated statistically significant differences in mean distances to reference sets between all pairs of body sites (stool, skin, nasal, saliva and vagina) at the phylum, class, order, family and genus levels. Using the distance to a single reference set was usually sufficient, but using both reference sets always worked well. The use of reference sets simplifies standard analyses of beta-diversity and facilitates the independent validation and combining of such data because others can compute distances to the same reference sets. Moreover, standard statistical methods for survival analysis, logistic regression and other procedures can be applied to vectors of mean distances to reference sets, thereby greatly expanding the potential uses of beta-diversity information. More work is needed to identify the best reference sets for particular applications.<br><br>https://github.com/NCI-biostats/microbiome-fixed-reference.<br><br>SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.}, }
@article {pmid29668682, year = {2018}, author = {Hannigan, GD and Duhaime, MB and Koutra, D and Schloss, PD}, title = {Biogeography and environmental conditions shape bacteriophage-bacteria networks across the human microbiome.}, journal = {PLoS computational biology}, volume = {14}, number = {4}, pages = {e1006099}, pmid = {29668682}, issn = {1553-7358}, support = {T32AI007528/NH/NIH HHS/United States ; T32 AI007528/AI/NIAID NIH HHS/United States ; U01 AI124255/AI/NIAID NIH HHS/United States ; P30 DK034933/DK/NIDDK NIH HHS/United States ; P30DK034933/NH/NIH HHS/United States ; U01AI124255/NH/NIH HHS/United States ; U19AI09087/NH/NIH HHS/United States ; }, mesh = {Bacteria/*genetics ; *Bacterial Physiological Phenomena ; Bacteriophages/*genetics/*physiology ; Computational Biology ; Diet ; Humans ; Metagenomics ; Microbial Consortia/genetics/physiology ; Microbiota/*genetics/*physiology ; Models, Biological ; Phylogeography ; Skin/microbiology/virology ; }, abstract = {Viruses and bacteria are critical components of the human microbiome and play important roles in health and disease. Most previous work has relied on studying bacteria and viruses independently, thereby reducing them to two separate communities. Such approaches are unable to capture how these microbial communities interact, such as through processes that maintain community robustness or allow phage-host populations to co-evolve. We implemented a network-based analytical approach to describe phage-bacteria network diversity throughout the human body. We built these community networks using a machine learning algorithm to predict which phages could infect which bacteria in a given microbiome. Our algorithm was applied to paired viral and bacterial metagenomic sequence sets from three previously published human cohorts. We organized the predicted interactions into networks that allowed us to evaluate phage-bacteria connectedness across the human body. We observed evidence that gut and skin network structures were person-specific and not conserved among cohabitating family members. High-fat diets appeared to be associated with less connected networks. Network structure differed between skin sites, with those exposed to the external environment being less connected and likely more susceptible to network degradation by microbial extinction events. This study quantified and contrasted the diversity of virome-microbiome networks across the human body and illustrated how environmental factors may influence phage-bacteria interactive dynamics. This work provides a baseline for future studies to better understand system perturbations, such as disease states, through ecological networks.}, }
@article {pmid29666626, year = {2018}, author = {Ichinohe, T and Miyama, T and Kawase, T and Honjo, Y and Kitaura, K and Sato, H and Shin-I, T and Suzuki, R}, title = {Next-Generation Immune Repertoire Sequencing as a Clue to Elucidate the Landscape of Immune Modulation by Host-Gut Microbiome Interactions.}, journal = {Frontiers in immunology}, volume = {9}, number = {}, pages = {668}, pmid = {29666626}, issn = {1664-3224}, mesh = {Adaptive Immunity ; Animals ; Gastrointestinal Microbiome/*immunology ; *High-Throughput Nucleotide Sequencing ; Homeostasis ; Humans ; }, abstract = {The human immune system is a fine network consisted of the innumerable numbers of functional cells that balance the immunity and tolerance against various endogenous and environmental challenges. Although advances in modern immunology have revealed a role of many unique immune cell subsets, technologies that enable us to capture the whole landscape of immune responses against specific antigens have been not available to date. Acquired immunity against various microorganisms including host microbiome is principally founded on T cell and B cell populations, each of which expresses antigen-specific receptors that define a unique clonotype. Over the past several years, high-throughput next-generation sequencing has been developed as a powerful tool to profile T- and B-cell receptor repertoires in a given individual at the single-cell level. Sophisticated immuno-bioinformatic analyses by use of this innovative methodology have been already implemented in clinical development of antibody engineering, vaccine design, and cellular immunotherapy. In this article, we aim to discuss the possible application of high-throughput immune receptor sequencing in the field of nutritional and intestinal immunology. Although there are still unsolved caveats, this emerging technology combined with single-cell transcriptomics/proteomics provides a critical tool to unveil the previously unrecognized principle of host-microbiome immune homeostasis. Accumulation of such knowledge will lead to the development of effective ways for personalized immune modulation through deeper understanding of the mechanisms by which the intestinal environment affects our immune ecosystem.}, }
@article {pmid29665135, year = {2019}, author = {Ponziani, FR and Bhoori, S and Castelli, C and Putignani, L and Rivoltini, L and Del Chierico, F and Sanguinetti, M and Morelli, D and Paroni Sterbini, F and Petito, V and Reddel, S and Calvani, R and Camisaschi, C and Picca, A and Tuccitto, A and Gasbarrini, A and Pompili, M and Mazzaferro, V}, title = {Hepatocellular Carcinoma Is Associated With Gut Microbiota Profile and Inflammation in Nonalcoholic Fatty Liver Disease.}, journal = {Hepatology (Baltimore, Md.)}, volume = {69}, number = {1}, pages = {107-120}, doi = {10.1002/hep.30036}, pmid = {29665135}, issn = {1527-3350}, support = {//Italian Ministry of Education, Universities and Research/International ; }, mesh = {Aged ; Carcinoma, Hepatocellular/*congenital/*microbiology ; Female ; *Gastrointestinal Microbiome ; Humans ; Inflammation/*complications ; Liver Cirrhosis/*complications ; Liver Neoplasms/*complications/*microbiology ; Male ; Middle Aged ; Non-alcoholic Fatty Liver Disease/*complications ; }, abstract = {The gut-liver axis plays a pivotal role in the pathogenesis of nonalcoholic fatty liver disease (NAFLD), which is the third leading cause of hepatocellular carcinoma (HCC) worldwide. However, the link between gut microbiota and hepatocarcinogenesis remains to be clarified. The aim of this study was to explore what features of the gut microbiota are associated with HCC in patients with cirrhosis and NAFLD. A consecutive series of patients with NAFLD-related cirrhosis and HCC (group 1, 21 patients), NAFLD-related cirrhosis without HCC (group 2, 20 patients), and healthy controls (group 3, 20 patients) was studied for gut microbiota profile, intestinal permeability, inflammatory status, and circulating mononuclear cells. We finally constructed a model depicting the most relevant correlations among these features, possibly involved in hepatocarcinogenesis. Patients with HCC showed increased levels of fecal calprotectin, while intestinal permeability was similar to patients with cirrhosis but without HCC. Plasma levels of interleukin 8 (IL8), IL13, chemokine (C-C motif) ligand (CCL) 3, CCL4, and CCL5 were higher in the HCC group and associated with an activated status of circulating monocytes. The fecal microbiota of the whole group of patients with cirrhosis showed higher abundance of Enterobacteriaceae and Streptococcus and a reduction in Akkermansia. Bacteroides and Ruminococcaceae were increased in the HCC group, while Bifidobacterium was reduced. Akkermansia and Bifidobacterium were inversely correlated with calprotectin concentration, which in turn was associated with humoral and cellular inflammatory markers. A similar behavior was also observed for Bacteroides. Conclusion: Our results suggest that in patients with cirrhosis and NAFLD the gut microbiota profile and systemic inflammation are significantly correlated and can concur in the process of hepatocarcinogenesis.}, }
@article {pmid29659479, year = {2018}, author = {Sudhakara, P and Gupta, A and Bhardwaj, A and Wilson, A}, title = {Oral Dysbiotic Communities and Their Implications in Systemic Diseases.}, journal = {Dentistry journal}, volume = {6}, number = {2}, pages = {}, pmid = {29659479}, issn = {2304-6767}, support = {R03 DE026526/DE/NIDCR NIH HHS/United States ; }, abstract = {The human body supports the growth of a wide array of microbial communities in various niches such as the oral cavity, gastro-intestinal and urogenital tracts, and on the surface of the skin. These host associated microbial communities include yet-un-cultivable bacteria and are influenced by various factors. Together, these communities of bacteria are referred to as the human microbiome. Human oral microbiome consists of both symbionts and pathobionts. Deviation from symbiosis among the bacterial community leads to &amp;ldquo;dysbiosis&amp;rdquo;, a state of community disturbance. Dysbiosis occurs due to many confounding factors that predispose a shift in the composition and relative abundance of microbial communities. Dysbiotic communities have been a major cause for many microbiome related systemic infections. Such dysbiosis is directed by certain important pathogens called the &amp;ldquo;keystone pathogens&amp;rdquo;, which can modulate community microbiome variations. One such persistent infection is oral infection, mainly periodontitis, where a wide array of causal organisms have been implied to systemic infections such as cardio vascular disease, diabetes mellitus, rheumatoid arthritis, and Alzheimer’s disease. The keystone pathogens co-occur with many yet-cultivable bacteria and their interactions lead to dysbiosis. This has been the focus of recent research. While immune evasion is one of the major modes that leads to dysbiosis, new processes and new virulence factors of bacteria have been shown to be involved in this important process that determines a disease or health state. This review focuses on such dysbiotic communities, their interactions, and their virulence factors that predispose the host to other systemic implications.}, }
@article {pmid29658784, year = {2018}, author = {Popic, V and Kuleshov, V and Snyder, M and Batzoglou, S}, title = {Fast Metagenomic Binning via Hashing and Bayesian Clustering.}, journal = {Journal of computational biology : a journal of computational molecular cell biology}, volume = {25}, number = {7}, pages = {677-688}, doi = {10.1089/cmb.2017.0250}, pmid = {29658784}, issn = {1557-8666}, mesh = {*Bayes Theorem ; Cluster Analysis ; Computational Biology/*statistics &amp; numerical data ; Humans ; Metagenome/genetics ; Metagenomics/*statistics &amp; numerical data ; Microbiota/*genetics ; }, abstract = {We introduce GATTACA, a framework for fast unsupervised binning of metagenomic contigs. Similar to recent approaches, GATTACA clusters contigs based on their coverage profiles across a large cohort of metagenomic samples; however, unlike previous methods that rely on read mapping, GATTACA quickly estimates these profiles from kmer counts stored in a compact index. This approach can result in over an order of magnitude speedup, while matching the accuracy of earlier methods on synthetic and real data benchmarks. It also provides a way to index metagenomic samples (e.g., from public repositories such as the Human Microbiome Project) offline once and reuse them across experiments; furthermore, the small size of the sample indices allows them to be easily transferred and stored. Leveraging the MinHash technique, GATTACA also provides an efficient way to identify publicly available metagenomic data that can be incorporated into the set of reference metagenomes to further improve binning accuracy. Thus, enabling easy indexing and reuse of publicly available metagenomic data sets, GATTACA makes accurate metagenomic analyses accessible to a much wider range of researchers.}, }
@article {pmid29657964, year = {2018}, author = {Whiteson, KL}, title = {Vive la Persistence: Engineering Human Microbiomes in the 21st Century.}, journal = {mSystems}, volume = {3}, number = {2}, pages = {}, pmid = {29657964}, issn = {2379-5077}, support = {UL1 TR001414/TR/NCATS NIH HHS/United States ; }, abstract = {I imagine a future in which children grow up with healthy microbial communities. Engineering human microbiomes might actually be achievable in the near future, as we enter an era of hunting for human-adapted bacterial strains and phages. Furthermore, breath metabolites could allow us to track whether a probiotic colonizes persistently or a phage has knocked down a microbe of interest. Recent successes with probiotics, such as bifidobacteria that can break down human milk oligosaccharides, are making a future in which infants are intentionally colonized with health-promoting strains seem less unlikely. Viruses that infect bacteria, bacteriophages, are also important for human health both because of their role in the human microbiome and because of their potential for use in phage therapy. Monitoring the outcome of microbiome-focused interventions with breath volatile sampling is also on the horizon, which could mean real-time tracking of microbial metabolite production. Studies of early life during microbiome assembly, when the potential for effective interventions to reduce disease risk is greatest, are essential.}, }
@article {pmid29654837, year = {2018}, author = {Seekatz, AM and Theriot, CM and Rao, K and Chang, YM and Freeman, AE and Kao, JY and Young, VB}, title = {Restoration of short chain fatty acid and bile acid metabolism following fecal microbiota transplantation in patients with recurrent Clostridium difficile infection.}, journal = {Anaerobe}, volume = {53}, number = {}, pages = {64-73}, pmid = {29654837}, issn = {1095-8274}, support = {UL1 TR000433/TR/NCATS NIH HHS/United States ; U19 AI090871/AI/NIAID NIH HHS/United States ; R21 AI120599/AI/NIAID NIH HHS/United States ; K01 GM109236/GM/NIGMS NIH HHS/United States ; P30 AG024824/AG/NIA NIH HHS/United States ; U01 AI124255/AI/NIAID NIH HHS/United States ; UL1 TR002240/TR/NCATS NIH HHS/United States ; R35 GM119438/GM/NIGMS NIH HHS/United States ; U24 DK097153/DK/NIDDK NIH HHS/United States ; }, mesh = {Adult ; Aged ; Bile Acids and Salts/*metabolism ; Clostridium Infections/*therapy ; Fatty Acids, Volatile/*metabolism ; *Fecal Microbiota Transplantation ; Female ; Gastrointestinal Microbiome ; Humans ; Longitudinal Studies ; Male ; Metabolomics ; Middle Aged ; RNA, Bacterial/genetics ; RNA, Ribosomal, 16S/genetics ; Secondary Prevention/*methods ; Sequence Analysis, DNA ; Young Adult ; }, abstract = {A significant proportion of individuals develop recurrent Clostridium difficile infection (CDI) following initial disease. Fecal microbiota transplantation (FMT), a highly effective treatment method for recurrent CDI, has been demonstrated to induce microbiota recovery. One of the proposed functions associated with restoration of colonization resistance against C. difficile has been recovery of bile acid metabolism. In this study, we aimed to assess recovery of short chain fatty acids (SCFAs) in addition to bile acids alongside microbial community structure in six patients with recurrent CDI following treatment with FMT over time. Using 16S rRNA gene-based sequencing, we observed marked similarity of the microbiota between recipients following FMT (n = 6, sampling up to 6 months post-FMT) and their respective donors. Sustained increases in the levels of the SCFAs butyrate, acetate, and propionate were observed post-FMT, and variable recovery over time was observed in the secondary bile acids deoxycholate and lithocholate. To correlate these changes with specific microbial taxa at an individual level, we applied a generalized estimating equation approach to model metabolite concentrations with the presence of specific members of the microbiota. Metabolites that increased following FMT were associated with bacteria classified within the Lachnospiraceae, Ruminococcaceae, and unclassified Clostridiales families. In contrast, members of these taxa were inversely associated with primary bile acids. The longitudinal aspect of this study allowed us to characterize individualized patterns of recovery, revealing variability between and within patients following FMT.}, }
@article {pmid29643839, year = {2018}, author = {Zhai, J and Kim, J and Knox, KS and Twigg, HL and Zhou, H and Zhou, JJ}, title = {Variance Component Selection With Applications to Microbiome Taxonomic Data.}, journal = {Frontiers in microbiology}, volume = {9}, number = {}, pages = {509}, pmid = {29643839}, issn = {1664-302X}, support = {R01 GM105785/GM/NIGMS NIH HHS/United States ; P30 ES006694/ES/NIEHS NIH HHS/United States ; K01 DK106116/DK/NIDDK NIH HHS/United States ; R01 GM053275/GM/NIGMS NIH HHS/United States ; U01 HL121831/HL/NHLBI NIH HHS/United States ; R01 HG006139/HG/NHGRI NIH HHS/United States ; U01 HL098960/HL/NHLBI NIH HHS/United States ; }, abstract = {High-throughput sequencing technology has enabled population-based studies of the role of the human microbiome in disease etiology and exposure response. Microbiome data are summarized as counts or composition of the bacterial taxa at different taxonomic levels. An important problem is to identify the bacterial taxa that are associated with a response. One method is to test the association of specific taxon with phenotypes in a linear mixed effect model, which incorporates phylogenetic information among bacterial communities. Another type of approaches consider all taxa in a joint model and achieves selection via penalization method, which ignores phylogenetic information. In this paper, we consider regression analysis by treating bacterial taxa at different level as multiple random effects. For each taxon, a kernel matrix is calculated based on distance measures in the phylogenetic tree and acts as one variance component in the joint model. Then taxonomic selection is achieved by the lasso (least absolute shrinkage and selection operator) penalty on variance components. Our method integrates biological information into the variable selection problem and greatly improves selection accuracies. Simulation studies demonstrate the superiority of our methods versus existing methods, for example, group-lasso. Finally, we apply our method to a longitudinal microbiome study of Human Immunodeficiency Virus (HIV) infected patients. We implement our method using the high performance computing language Julia. Software and detailed documentation are freely available at https://github.com/JingZhai63/VCselection.}, }
@article {pmid29641531, year = {2018}, author = {Fan, X and Peters, BA and Min, D and Ahn, J and Hayes, RB}, title = {Comparison of the oral microbiome in mouthwash and whole saliva samples.}, journal = {PloS one}, volume = {13}, number = {4}, pages = {e0194729}, pmid = {29641531}, issn = {1932-6203}, support = {R01 CA159036/CA/NCI NIH HHS/United States ; R01 CA164964/CA/NCI NIH HHS/United States ; }, mesh = {Adult ; Aged ; Bacteria/*classification ; Cohort Studies ; DNA, Bacterial/analysis ; Healthy Volunteers ; Humans ; Microbiota/*genetics ; Middle Aged ; Mouth Mucosa/microbiology ; *Mouthwashes ; Phylogeny ; Prospective Studies ; RNA, Ribosomal, 16S/genetics ; Saliva/*microbiology ; Specimen Handling ; }, abstract = {Population-based epidemiologic studies can provide important insight regarding the role of the microbiome in human health and disease. Buccal cells samples using commercial mouthwash have been obtained in large prospective cohorts for the purpose of studying human genomic DNA. We aimed to better understand if these mouthwash samples are also a valid resource for the study of the oral microbiome. We collected one saliva sample and one Scope mouthwash sample from 10 healthy subjects. Bacterial 16S rRNA genes from both types of samples were amplified, sequenced, and assigned to bacterial taxa. We comprehensively compared these paired samples for bacterial community composition and individual taxonomic abundance. We found that mouthwash samples yielded similar amount of bacterial DNA as saliva samples (p from Student's t-test for paired samples = 0.92). Additionally, the paired samples had similar within sample diversity (p from = 0.33 for richness, and p = 0.51 for Shannon index), and clustered as pairs for diversity when analyzed by unsupervised hierarchical cluster analysis. No significant difference was found in the paired samples with respect to the taxonomic abundance of major bacterial phyla, Bacteroidetes, Firmicutes, Proteobacteria, Fusobacteria, and Actinobacteria (FDR adjusted q values from Wilcoxin signed-rank test = 0.15, 0.15, 0.87, 1.00 and 0.15, respectively), and all identified genera, including genus Streptococcus (q = 0.21), Prevotella (q = 0.25), Neisseria (q = 0.37), Veillonella (q = 0.73), Fusobacterium (q = 0.19), and Porphyromonas (q = 0.60). These results show that mouthwash samples perform similarly to saliva samples for analysis of the oral microbiome. Mouthwash samples collected originally for analysis of human DNA are also a resource suitable for human microbiome research.}, }
@article {pmid29641525, year = {2018}, author = {Weber, KS and Bridgewater, LC and Jensen, JL and Breakwell, DP and Nielsen, BL and Johnson, SM}, title = {Personal microbiome analysis improves student engagement and interest in Immunology, Molecular Biology, and Genomics undergraduate courses.}, journal = {PloS one}, volume = {13}, number = {4}, pages = {e0193696}, pmid = {29641525}, issn = {1932-6203}, mesh = {Allergy and Immunology/*education ; *Attitude ; Genomics/*education ; Humans ; *Microbiota ; Molecular Biology/*education ; *Students ; Universities ; }, abstract = {A critical area of emphasis for science educators is the identification of effective means of teaching and engaging undergraduate students. Personal microbiome analysis is a means of identifying the microbial communities found on or in our body. We hypothesized the use of personal microbiome analysis in the classroom could improve science education by making courses more applied and engaging for undergraduate students. We determined to test this prediction in three Brigham Young University undergraduate courses: Immunology, Advanced Molecular Biology Laboratory, and Genomics. These three courses have a two-week microbiome unit and students during the 2016 semester students could submit their own personal microbiome kit or use the demo data, whereas during the 2017 semester students were given access to microbiome data from an anonymous individual. The students were surveyed before, during, and after the human microbiome unit to determine whether analyzing their own personal microbiome data, compared to analyzing demo microbiome data, impacted student engagement and interest. We found that personal microbiome analysis significantly enhanced the engagement and interest of students while completing microbiome assignments, the self-reported time students spent researching the microbiome during the two week microbiome unit, and the attitudes of students regarding the course overall. Thus, we found that integrating personal microbiome analysis in the classroom was a powerful means of improving student engagement and interest in undergraduate science courses.}, }
@article {pmid29636512, year = {2018}, author = {Pechal, JL and Schmidt, CJ and Jordan, HR and Benbow, ME}, title = {A large-scale survey of the postmortem human microbiome, and its potential to provide insight into the living health condition.}, journal = {Scientific reports}, volume = {8}, number = {1}, pages = {5724}, pmid = {29636512}, issn = {2045-2322}, mesh = {*Autopsy ; Computational Biology/methods ; Cross-Sectional Studies ; Humans ; Metagenome ; Metagenomics/methods ; *Microbiota ; Time Factors ; }, abstract = {The microbiome plays many roles in human health, often through the exclusive lens of clinical interest. The inevitable end point for all living hosts, death, has its own altered microbiome configurations. However, little is understood about the ecology and changes of microbial communities after death, or their potential utility for understanding the health condition of the recently living. Here we reveal distinct postmortem microbiomes of human hosts from a large-scale survey of death cases representing a predominantly urban population, and demonstrated these microbiomes reflected antemortem health conditions within 24-48 hours of death. Our results characterized microbial community structure and predicted function from 188 cases representing a cross-section of an industrial-urban population. We found strong niche differentiation of anatomic habitat and microbial community turnover based on topographical distribution. Microbial community stability was documented up to two days after death. Additionally, we observed a positive relationship between cell motility and time since host death. Interestingly, we discovered evidence that microbial biodiversity is a predictor of antemortem host health condition (e.g., heart disease). These findings improve the understanding of postmortem host microbiota dynamics, and provide a robust dataset to test the postmortem microbiome as a tool for assessing health conditions in living populations.}, }
@article {pmid29636439, year = {2018}, author = {Brown, CT and Xiong, W and Olm, MR and Thomas, BC and Baker, R and Firek, B and Morowitz, MJ and Hettich, RL and Banfield, JF}, title = {Hospitalized Premature Infants Are Colonized by Related Bacterial Strains with Distinct Proteomic Profiles.}, journal = {mBio}, volume = {9}, number = {2}, pages = {}, pmid = {29636439}, issn = {2150-7511}, support = {R01 AI092531/AI/NIAID NIH HHS/United States ; R01 GM103600/GM/NIGMS NIH HHS/United States ; }, mesh = {Bacteria/*chemistry/classification/genetics ; Biota ; Enterocolitis, Necrotizing/microbiology/pathology ; Feces/microbiology ; Female ; *Gastrointestinal Microbiome ; *Hospitalization ; Humans ; Infant, Newborn ; *Infant, Premature ; Male ; Metagenome ; Metagenomics ; *Microbiota ; Proteome/*analysis ; Proteomics ; }, abstract = {During the first weeks of life, microbial colonization of the gut impacts human immune system maturation and other developmental processes. In premature infants, aberrant colonization has been implicated in the onset of necrotizing enterocolitis (NEC), a life-threatening intestinal disease. To study the premature infant gut colonization process, genome-resolved metagenomics was conducted on 343 fecal samples collected during the first 3 months of life from 35 premature infants housed in a neonatal intensive care unit, 14 of whom developed NEC, and metaproteomic measurements were made on 87 samples. Microbial community composition and proteomic profiles remained relatively stable on the time scale of a week, but the proteome was more variable. Although genetically similar organisms colonized many infants, most infants were colonized by distinct strains with metabolic profiles that could be distinguished using metaproteomics. Microbiome composition correlated with infant, antibiotics administration, and NEC diagnosis. Communities were found to cluster into seven primary types, and community type switched within infants, sometimes multiple times. Interestingly, some communities sampled from the same infant at subsequent time points clustered with those of other infants. In some cases, switches preceded onset of NEC; however, no species or community type could account for NEC across the majority of infants. In addition to a correlation of protein abundances with organism replication rates, we found that organism proteomes correlated with overall community composition. Thus, this genome-resolved proteomics study demonstrated that the contributions of individual organisms to microbiome development depend on microbial community context.IMPORTANCE Humans are colonized by microbes at birth, a process that is important to health and development. However, much remains to be known about the fine-scale microbial dynamics that occur during the colonization period. We conducted a genome-resolved study of microbial community composition, replication rates, and proteomes during the first 3 months of life of both healthy and sick premature infants. Infants were found to be colonized by similar microbes, but each underwent a distinct colonization trajectory. Interestingly, related microbes colonizing different infants were found to have distinct proteomes, indicating that microbiome function is not only driven by which organisms are present, but also largely depends on microbial responses to the unique set of physiological conditions in the infant gut.}, }
@article {pmid29634682, year = {2018}, author = {Gilbert, JA and Blaser, MJ and Caporaso, JG and Jansson, JK and Lynch, SV and Knight, R}, title = {Current understanding of the human microbiome.}, journal = {Nature medicine}, volume = {24}, number = {4}, pages = {392-400}, pmid = {29634682}, issn = {1546-170X}, support = {U54 CA143925/CA/NCI NIH HHS/United States ; }, mesh = {Biomarkers/metabolism ; Disease ; Humans ; Life Style ; *Microbiota ; Precision Medicine ; Translational Research, Biomedical ; }, abstract = {Our understanding of the link between the human microbiome and disease, including obesity, inflammatory bowel disease, arthritis and autism, is rapidly expanding. Improvements in the throughput and accuracy of DNA sequencing of the genomes of microbial communities that are associated with human samples, complemented by analysis of transcriptomes, proteomes, metabolomes and immunomes and by mechanistic experiments in model systems, have vastly improved our ability to understand the structure and function of the microbiome in both diseased and healthy states. However, many challenges remain. In this review, we focus on studies in humans to describe these challenges and propose strategies that leverage existing knowledge to move rapidly from correlation to causation and ultimately to translation into therapies.}, }
@article {pmid29633119, year = {2018}, author = {Skowron, KB and Shogan, BD and Rubin, DT and Hyman, NH}, title = {The New Frontier: the Intestinal Microbiome and Surgery.}, journal = {Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract}, volume = {22}, number = {7}, pages = {1277-1285}, pmid = {29633119}, issn = {1873-4626}, mesh = {Anastomotic Leak/*microbiology ; Digestive System Surgical Procedures/*adverse effects ; *Gastrointestinal Microbiome ; Humans ; Intestinal Mucosa/microbiology ; Microbiota/*physiology ; }, abstract = {The microbiome exerts a remarkable effect on human physiology. The study of the human-microbiome relationship is a burgeoning field with great potential to improve our understanding of health and disease. In this review, we address common surgical problems influenced by the human microbiome and explore what is thus far known about this relationship. These include inflammatory bowel disease, colorectal neoplasms, and diverticular disease. We will also discuss the effect of the microbiome on surgical complications, specifically anastomotic leak. We hope that further research in this field will enlighten our management of these and other surgical problems.}, }
@article {pmid29629420, year = {2018}, author = {Langille, MGI}, title = {Exploring Linkages between Taxonomic and Functional Profiles of the Human Microbiome.}, journal = {mSystems}, volume = {3}, number = {2}, pages = {}, pmid = {29629420}, issn = {2379-5077}, abstract = {Microbiome studies typically focus on characterizing the taxonomic and functional profiles of the microbes within a community. Functional profiling is generally thought to be superior to taxonomic profiling for investigating human-microbe interactions, but there are several limitations and challenges to existing approaches. This Perspective discusses the current sequencing and bioinformatic methods for producing taxonomic and functional profiles, recent studies utilizing and comparing these technologies, and the existing challenges and limitations of these data. In addition, functional versus taxonomic conservation across the population is questioned, while future research that focuses on investigating the taxonomic diversity of microbial functions is proposed.}, }
@article {pmid29629416, year = {2018}, author = {Lieberman, TD}, title = {Seven Billion Microcosms: Evolution within Human Microbiomes.}, journal = {mSystems}, volume = {3}, number = {2}, pages = {}, pmid = {29629416}, issn = {2379-5077}, abstract = {Rational microbiome-based therapies may one day treat a wide range of diseases and promote wellness. Yet, we are still limited in our abilities to employ such therapies and to predict which bacterial strains have the potential to stably colonize a person. The Lieberman laboratory is working to close this knowledge gap and to develop an understanding of how individual species and strains behave in the human microbiome, including with regard to their niche ranges, survival strategies, and the degree to which they adapt to individual people. We employ system-level approaches, with a particular emphasis on using de novo mutations and evolutionary inference to reconstruct the history of bacterial lineages within individuals.}, }
@article {pmid29629415, year = {2018}, author = {David, LA}, title = {Toward Personalized Control of Human Gut Bacterial Communities.}, journal = {mSystems}, volume = {3}, number = {2}, pages = {}, pmid = {29629415}, issn = {2379-5077}, support = {R01 DK116187/DK/NIDDK NIH HHS/United States ; R24 DK110492/DK/NIDDK NIH HHS/United States ; }, abstract = {A key challenge in microbiology will be developing tools for manipulating human gut bacterial communities. Our ability to predict and control the dynamics of these communities is now in its infancy. To manage human gut microbiota, I am developing methods in three research domains. First, I am refining in vitro tools to experimentally study gut microbes at high throughput and in controlled settings. Second, I am adapting "big data" techniques to overcome statistical challenges confronting microbiota modeling. Third, I am testing study designs that can streamline human testing of microbiota manipulations. Assembling these methods creates new challenges, including training scientists who can work across disciplines such as engineering, ecology, and medicine. Nevertheless, I envision that overcoming these obstacles will enable my group to construct platforms that can personalize microbiota treatments, particularly ones based on diet. More broadly, I anticipate that such platforms will have applications across fields such as agriculture, biotechnology, and environmental management.}, }
@article {pmid29627609, year = {2018}, author = {Lu, W and Negi, SS and Schein, CH and Maleki, SJ and Hurlburt, BK and Braun, W}, title = {Distinguishing allergens from non-allergenic homologues using Physical-Chemical Property (PCP) motifs.}, journal = {Molecular immunology}, volume = {99}, number = {}, pages = {1-8}, pmid = {29627609}, issn = {1872-9142}, support = {R21 AI109090/AI/NIAID NIH HHS/United States ; }, mesh = {Allergens/*chemistry/*immunology ; Cross Reactions/immunology ; Epitopes/chemistry/immunology ; Fruit/chemistry/immunology ; Humans ; Immunoglobulin E/chemistry/immunology ; Nuts/chemistry/immunology ; Plant Proteins/chemistry/immunology ; Pollen/chemistry/immunology ; Polysaccharide-Lyases/chemistry/immunology ; Profilins/chemistry/immunology ; }, abstract = {Quantitative guidelines to distinguish allergenic proteins from related, but non-allergenic ones are urgently needed for regulatory agencies, biotech companies and physicians. In a previous study, we found that allergenic proteins populate a relatively small number of protein families, as characterized by the Pfam database. However, these families also contain non-allergenic proteins, meaning that allergenic determinants must lie within more discrete regions of the sequence. Thus, new methods are needed to discriminate allergenic proteins within those families. Physical-Chemical Properties (PCP)-motifs specific for allergens within a Pfam class were determined for 17 highly populated protein domains. A novel scoring method based on PCP-motifs that characterize known allergenic proteins within these families was developed, and validated for those domains. The motif scores distinguished sequences of allergens from a large selection of 80,000 randomly selected non-allergenic sequences. The motif scores for the birch pollen allergen (Bet v 1) family, which also contains related fruit and nut allergens, correlated better than global sequence similarities with clinically observed cross-reactivities among those allergens. Further, we demonstrated that the average scores of allergen specific motifs for allergenic profilins are significantly different from the scores of non-allergenic profilins. Several of the selective motifs coincide with experimentally determined IgE epitopes of allergenic profilins. The motifs also discriminated allergenic pectate lyases, including Jun a 1 from mountain cedar pollen, from similar proteins in the human microbiome, which can be assumed to be non-allergens. The latter lacked key motifs characteristic of the known allergens, some of which correlate with known IgE binding sites.}, }
@article {pmid29623445, year = {2018}, author = {Ho, HE and Bunyavanich, S}, title = {Role of the Microbiome in Food Allergy.}, journal = {Current allergy and asthma reports}, volume = {18}, number = {4}, pages = {27}, pmid = {29623445}, issn = {1534-6315}, mesh = {Animals ; Child ; Dysbiosis/*immunology ; Food Hypersensitivity/*microbiology ; Humans ; Immune System/physiology ; Immune Tolerance/*immunology ; Microbiota/*physiology ; Probiotics ; }, abstract = {PURPOSE OF REVIEW: Resident microbial communities likely modify risk for allergic disorders, including food allergy. We review epidemiologic studies linking microbial exposures to food allergy risk and discuss the mechanisms by which the microbiome may modulate oral tolerance. We additionally address ongoing translational efforts in human microbiome studies.<br><br>RECENT FINDINGS: Epidemiologic studies and murine models support that altered microbial exposures and colonization in early life modify food allergy risk. Differential microbiota confer protection or susceptibility to food allergy by modulating the regulatory tone of the mucosal immune system. Recent efforts are focused on the identification of bacterial strains necessary for oral tolerance in human and microbial-based clinical trials. Early childhood appears to be critical for the colonization of a diverse microbiota necessary for the induction and maintenance of oral tolerance. Identification and functional evaluation of protective commensal microbes will inform strategies for the prevention and treatment of food allergy.}, }
@article {pmid29619642, year = {2018}, author = {Srinivasan, VB and Angrasan, M and Chandel, N and Rajamohan, G}, title = {Genome sequence and comparative analysis of Bacillus cereus BC04, reveals genetic diversity and alterations for antimicrobial resistance.}, journal = {Functional &amp; integrative genomics}, volume = {18}, number = {4}, pages = {477-487}, pmid = {29619642}, issn = {1438-7948}, support = {BT/HRD/NBA/34/01/2012//Department of Biotechnology , Ministry of Science and Technology/ ; BT/01/IYBA/2009//Department of Biotechnology , Ministry of Science and Technology/ ; BSC0119H//Council of Scientific and Industrial Research/ ; SB/YS/LS-177/2014//Science and Engineering Research Board/ ; }, mesh = {Bacillus cereus/classification/drug effects/*genetics ; Drug Resistance, Bacterial/*genetics ; *Genome, Bacterial ; Molecular Sequence Annotation ; Phylogeny ; *Polymorphism, Genetic ; }, abstract = {In this study, we delineated the genome sequence of a Bacillus cereus strain BC04 isolated from a stool sample in India. The draft genome is 5.1 Mb in size and consists of total 109 scaffolds, GC content is 35.2% with 5182 coding genes. The comparative analysis with other completely sequenced genomes highlights the unique presence of genomic islands, hemolysin, capsular synthetic protein, modifying enzymes accC7 and catA15, regulators of antibiotic resistance MarR and LysR with annotated functions related to virulence, stress response, and antimicrobial resistance. Overall, this study not only signifies the genetic diversity in gut isolate BC04 in particular, but also pinpoints the presence of unique genes possessed by B. cereus which can be pertinently exploited to design novel drugs and intervention strategies for the treatment of food borne diseases.}, }
@article {pmid29617920, year = {2018}, author = {Demmer, RT}, title = {Invited Commentary: The Microbiome and Population Health-Considerations for Enhancing Study Design and Data Analysis in Observational and Interventional Epidemiology.}, journal = {American journal of epidemiology}, volume = {187}, number = {6}, pages = {1291-1294}, pmid = {29617920}, issn = {1476-6256}, support = {R01 DK102932/DK/NIDDK NIH HHS/United States ; }, mesh = {Data Analysis ; Epidemiologic Studies ; Humans ; *Microbiota ; *Population Health ; Research Design ; }, abstract = {Measurement and characterization of the human microbiome in large population-based human studies has recently become a reality secondary to technological advances in high-throughput DNA sequencing. These advances bring new challenges and knowledge gaps for study planning, data analysis, and interpretation that are novel to large-scale epidemiologic studies. In this issue of the Journal, Sinha et al. (Am J Epidemiol. 2018;187(6):1282-1290) have provided data with which to inform statistical power and sample size requirements for microbiome studies in population-based settings. This work serves as a helpful starting point for study planning while also serving as a springboard for discussion regarding additional considerations for improving microbiome research. This commentary emphasizes the importance of selecting microbiome metrics appropriate for the biological hypothesis under investigation, as well as the need for new analytical tools that can better capitalize on the unique yet rich information contained in microbiome data sets.}, }
@article {pmid29608646, year = {2018}, author = {Sinha, R and Goedert, JJ and Vogtmann, E and Hua, X and Porras, C and Hayes, R and Safaeian, M and Yu, G and Sampson, J and Ahn, J and Shi, J}, title = {Quantification of Human Microbiome Stability Over 6 Months: Implications for Epidemiologic Studies.}, journal = {American journal of epidemiology}, volume = {187}, number = {6}, pages = {1282-1290}, pmid = {29608646}, issn = {1476-6256}, support = {R01 CA164964/CA/NCI NIH HHS/United States ; R03 CA159414/CA/NCI NIH HHS/United States ; }, mesh = {Feces/microbiology ; Female ; *Gastrointestinal Microbiome ; Humans ; Male ; Time Factors ; }, abstract = {Temporal variation in microbiome measurements can reduce statistical power in research studies. Quantification of this variation is essential for designing studies of chronic disease. We analyzed 16S ribosomal RNA profiles in paired biological specimens separated by 6 months from 3 studies conducted during 1985-2013 (a National Cancer Institute colorectal cancer study, a Costa Rica study, and the Human Microbiome Project). We evaluated temporal stability by calculating intraclass correlation coefficients (ICCs). Sample sizes needed in order to detect microbiome differences between equal numbers of cases and controls for a nested case-control design were calculated on the basis of estimated ICCs. Across body sites, 12 phylum-level ICCs were greater than 0.5. Similarly, 11 alpha-diversity ICCs were greater than 0.5. Fecal beta-diversity estimates had ICCs over 0.5. For a single collection with most microbiome metrics, detecting an odds ratio of 2.0 would require 300-500 cases when matching 1 case to 1 control at P = 0.05. Use of 2 or 3 sequential specimens reduces the number of required subjects by 40%-50% for low-ICC metrics. Relative abundances of major phyla and alpha-diversity metrics have low temporal stability. Thus, detecting associations of moderate effect size with these metrics will require large sample sizes. Because beta diversity for feces is reasonably stable over time, smaller sample sizes can detect associations with community composition. Sequential prediagnostic specimens from thousands of prospectively ascertained cases are required to detect modest disease associations with particular microbiome metrics.}, }
@article {pmid29596364, year = {2018}, author = {Vallone, C and Rigon, G and Gulia, C and Baffa, A and Votino, R and Morosetti, G and Zaami, S and Briganti, V and Catania, F and Gaffi, M and Nucciotti, R and Costantini, FM and Piergentili, R and Putignani, L and Signore, F}, title = {Non-Coding RNAs and Endometrial Cancer.}, journal = {Genes}, volume = {9}, number = {4}, pages = {}, pmid = {29596364}, issn = {2073-4425}, abstract = {Non-coding RNAs (ncRNAs) are involved in the regulation of cell metabolism and neoplastic transformation. Recent studies have tried to clarify the significance of these information carriers in the genesis and progression of various cancers and their use as biomarkers for the disease; possible targets for the inhibition of growth and invasion by the neoplastic cells have been suggested. The significance of ncRNAs in lung cancer, bladder cancer, kidney cancer, and melanoma has been amply investigated with important results. Recently, the role of long non-coding RNAs (lncRNAs) has also been included in cancer studies. Studies on the relation between endometrial cancer (EC) and ncRNAs, such as small ncRNAs or micro RNAs (miRNAs), transfer RNAs (tRNAs), ribosomal RNAs (rRNAs), antisense RNAs (asRNAs), small nuclear RNAs (snRNAs), Piwi-interacting RNAs (piRNAs), small nucleolar RNAs (snoRNAs), competing endogenous RNAs (ceRNAs), lncRNAs, and long intergenic ncRNAs (lincRNAs) have been published. The recent literature produced in the last three years was extracted from PubMed by two independent readers, which was then selected for the possible relation between ncRNAs, oncogenesis in general, and EC in particular.}, }
@article {pmid29570689, year = {2018}, author = {Cinelli, G and Fabrizi, M and Ravà, L and Signore, F and Vernocchi, P and Semeraro, M and Vallone, C and Lanciotti, R and Ciofi Degli Atti, M and Manco, M}, title = {Association between Maternal and Foetal Erythrocyte Fatty Acid Profiles and Birth Weight.}, journal = {Nutrients}, volume = {10}, number = {4}, pages = {}, pmid = {29570689}, issn = {2072-6643}, mesh = {Adult ; *Birth Weight ; Erythrocytes/*metabolism ; Fatty Acids/adverse effects/*blood ; Fatty Acids, Omega-6/blood ; Female ; Fetal Blood/*metabolism ; Gestational Age ; Humans ; Infant, Newborn ; *Infant, Small for Gestational Age ; Maternal Nutritional Physiological Phenomena ; Nutritional Status ; Pregnancy ; Risk Factors ; }, abstract = {Regular foetal development is crucial for assuring good health status in the offspring. The quality and quantity of maternal dietary fatty acids (FAs) can affect growth. The study aimed to: (1) investigate the association of maternal/foetal lipid profiles with birth weight (BW); and (2) compare these profiles in small, appropriate, and large for gestational age (SGA, AGA, and LGA) infants. FAs were measured in erythrocyte membranes using gas chromatography analysis in 607 mother-infant pairs (316 males, 52.1%). In the quantile regression, a significant association between BW and levels of maternal linoleic acid (LA; C18:2, n-6; coefficient: 18.66; p = 0.010), arachidonic acid (AA; C20:4, n-6; coefficient: 11.35; p = 0.007), docosahexaenoic acid (DHA; C22:6, n-3; coefficient: 29.73; p = 0.007), polyunsaturated FAs (coefficient: 8.55; p = 0.001), foetal DHA (coefficient: -22.82; p = 0.037), and saturated FAs (coefficient: -65.41; p = 0.002) was found. Myristic (C14:0) and pentadecanoic acids (C15:0), both maternal (p = 0.000; p = 0.017) and foetal (p = 0.009; p = 0.002), and maternal erucic acid (C22:1, n-9; p = 0.026) were found at higher levels in SGA infants as compared to AGA ones. Conversely, maternal LA, AA, and omega 6 FAs levels were higher in AGA infants (p = 0.037; p = 0.003; p = 0.026, respectively). Maternal and foetal polyunsaturated and omega 6 FAs levels are positively related to BW, while a lipid profile rich in saturated FAs and erucic acid may influence the risk of SGA.}, }
@article {pmid29568746, year = {2018}, author = {Wu, H and Cai, L and Li, D and Wang, X and Zhao, S and Zou, F and Zhou, K}, title = {Metagenomics Biomarkers Selected for Prediction of Three Different Diseases in Chinese Population.}, journal = {BioMed research international}, volume = {2018}, number = {}, pages = {2936257}, pmid = {29568746}, issn = {2314-6141}, mesh = {Algorithms ; Arthritis, Rheumatoid/*microbiology ; Asian People/*genetics ; Biomarkers/*metabolism ; Diabetes Mellitus, Type 2/*microbiology ; Dysbiosis/genetics ; Female ; Humans ; Liver Cirrhosis/*microbiology ; Male ; Metagenome/*genetics ; Metagenomics/methods ; Microbiota/*genetics ; Middle Aged ; ROC Curve ; }, abstract = {The dysbiosis of human microbiome has been proven to be associated with the development of many human diseases. Metagenome sequencing emerges as a powerful tool to investigate the effects of microbiome on diseases. Identification of human gut microbiome markers associated with abnormal phenotypes may facilitate feature selection for multiclass classification. Compared with binary classifiers, multiclass classification models deploy more complex discriminative patterns. Here, we developed a pipeline to address the challenging characterization of multilabel samples. In this study, a total of 300 biomarkers were selected from the microbiome of 806 Chinese individuals (383 controls, 170 with type 2 diabetes, 130 with rheumatoid arthritis, and 123 with liver cirrhosis), and then logistic regression prediction algorithm was applied to those markers as the model intrinsic features. The estimated model produced an F1 score of 0.9142, which was better than other popular classification methods, and an average receiver operating characteristic (ROC) of 0.9475 showed a significant correlation between these selected biomarkers from microbiome and corresponding phenotypes. The results from this study indicate that machine learning is a vital tool in data mining from microbiome in order to identify disease-related biomarkers, which may contribute to the application of microbiome-based precision medicine in the future.}, }
@article {pmid29568289, year = {2018}, author = {Flores Saiffe Farías, A and Mendizabal, AP and Morales, JA}, title = {An Ontology Systems Approach on Human Brain Expression and Metaproteomics.}, journal = {Frontiers in microbiology}, volume = {9}, number = {}, pages = {406}, pmid = {29568289}, issn = {1664-302X}, abstract = {Research in the last decade has shown growing evidence of the gut microbiota influence on brain physiology. While many mechanisms of this influence have been proposed in animal models, most studies in humans are the result of a pathology-dysbiosis association and very few have related the presence of certain taxa with brain substructures or molecular pathways. In this paper, we associated the functional ontologies in the differential expression of brain substructures from the Allen Brain Atlas database, with those of the metaproteome from the Human Microbiome Project. Our results showed several coherent clustered ontologies where many taxa could influence brain expression and physiology. A detailed analysis of psychobiotics showed specific slim ontologies functionally associated with substructures in the basal ganglia and cerebellar cortex. Some of the most relevant slim ontology groups are related to Ion transport, Membrane potential, Synapse, DNA and RNA metabolism, and Antigen processing, while the most relevant neuropathology found was Parkinson disease. In some of these cases, new hypothetical gut microbiota-brain interaction pathways are proposed.}, }
@article {pmid29566913, year = {2017}, author = {Ferreira, AK and Mambelli, LI and Pillai, SY}, title = {Intervening in disease through genetically-modified bacteria.}, journal = {Best practice &amp; research. Clinical gastroenterology}, volume = {31}, number = {6}, pages = {693-697}, doi = {10.1016/j.bpg.2017.09.017}, pmid = {29566913}, issn = {1532-1916}, mesh = {Bacteria/growth &amp; development/*pathogenicity ; Disease/*etiology ; Humans ; }, abstract = {The comprehension of the molecular basis of different diseases is rapidly being dissected as a consequence of advancing technology. Consequently, proteins with potential therapeutic usefulness, including cytokines and signaling molecules have been identified in the last decades. However, their clinical use is hampered by disadvantageous functional and economic considerations. One of the most important of these considerations is targeted topical delivery and also the synthesis of such proteins, which for intravenous use requires rigorous purification whereas proteins often do not withstand digestive degradation and thus cannot be applied per os. Recently, the idea of using genetically modified bacteria has emerged as an attempt to evade these important barriers. Using such bacteria can deliver therapeutic proteins or other molecules at place of disease, especially when disease is at a mucosal surface. Further, whereas intravenously applied therapeutic proteins require expensive methodology in order to become endotoxin-free, this is not necessary for local application of therapeutic proteins in the intestine. In addition, once created further propagation of genetically modified bacteria is both cheap and requires relatively little in conditioning with respect to transport of the medication, making such organisms also suitable for combating disease in developing countries with poor infrastructure. Although first human trials with such bacteria were already performed more as a decade ago, the recent revolution in our understanding of the role of human gut microbiome in health and diseases has unleashed a revolution in this field resulting in a plethora of potential novel prophylactic and therapeutic intervention against disease onset and development employing such organisms. Today, the engineering of human microbiome for health benefits and related applications now chances many aspects of biology, nanotechnology and chemistry. Here, we review genetically modified bacteria methodology as possible carriers of drug delivering and provided the origin and inspirations for new drug delivery systems.}, }
@article {pmid29566911, year = {2017}, author = {Konstantinov, SR}, title = {Diet, microbiome, and colorectal cancer.}, journal = {Best practice &amp; research. Clinical gastroenterology}, volume = {31}, number = {6}, pages = {675-681}, doi = {10.1016/j.bpg.2017.09.007}, pmid = {29566911}, issn = {1532-1916}, mesh = {Colorectal Neoplasms/*immunology/pathology ; *Diet ; Humans ; Microbiota/*immunology ; }, abstract = {The scientific interests in the colorectal cancer (CRC) associated microbiome have increased significantly in the past decade. Mechanistically, several members of the human microbiome and products thereof have been implicated as inductors of the pathogenic inflammation related to CRC. Conversely, the activities of the human intestinal microbial community influenced by specific diet might confer a protective effect against the CRC risks and progression. As the microbiome is both a key contributor and one of the tools to prevent CRC, the current review gives a summary of the CRC-associated microbiome and the dietary strategies relevant to CRC. As more evidences become available, new microbiome-based treatments and specific diets may emerge to reduce the CRC risk and improve CRC patients' quality of life.}, }
@article {pmid29557050, year = {2018}, author = {Ezcurra, M}, title = {Dissecting cause and effect in host-microbiome interactions using the combined worm-bug model system.}, journal = {Biogerontology}, volume = {19}, number = {6}, pages = {567-578}, pmid = {29557050}, issn = {1573-6768}, mesh = {Animals ; Bacillus subtilis/physiology ; Biofilms ; Caenorhabditis elegans/*microbiology ; Dysbiosis/immunology/*microbiology ; Escherichia coli/physiology ; Folic Acid/metabolism ; *Gastrointestinal Microbiome ; *Host Microbial Interactions ; Humans ; *Longevity ; *Models, Biological ; Nitric Acid/metabolism ; }, abstract = {High-throughput molecular studies are greatly advancing our knowledge of the human microbiome and its specific role in governing health and disease states. A myriad of ongoing studies aim at identifying links between microbial community disequilibria (dysbiosis) and human diseases. However, due to the inherent complexity and heterogeneity of the human microbiome we need robust experimental models that allow the systematic manipulation of variables to test the multitude of hypotheses arisen from large-scale 'meta-omic' projects. The nematode C. elegans combined with bacterial models offers an avenue to dissect cause and effect in host-microbiome interactions. This combined model allows the genetic manipulation of both host and microbial genetics and the use of a variety of tools, to identify pathways affecting host health. A number of recent high impact studies have used C. elegans to identify microbial pathways affecting ageing and longevity, demonstrating the power of the combined C. elegans-bacterial model. Here I will review the current state of the field, what we have learned from using C. elegans to study gut microbiome and host interactions, and the potential of using this model system in the future.}, }
@article {pmid29556544, year = {2018}, author = {Turnbaugh, PJ}, title = {Making Millennial Medicine More Meta.}, journal = {mSystems}, volume = {3}, number = {2}, pages = {}, pmid = {29556544}, issn = {2379-5077}, support = {R01 HL122593/HL/NHLBI NIH HHS/United States ; }, abstract = {Although the importance of human genetic polymorphisms in therapeutic outcomes is well established, the role of specific genotypic or copy number variants in our "second genome" (the microbiome) has been largely overlooked. In this Perspective, I will discuss three major barriers to integrating metagenomics into pharmacology, highlighting ongoing research by us and others that has begun to shed light on the mechanisms that link the human microbiome to the efficacy and toxicity of small-molecule and biological therapies. The challenges for the next 5 years and beyond are many, requiring interdisciplinary scientific teams working at the interface of chemistry and biology, and a consideration of far more variables than traditionally included in pharmacological modeling. However, the potential benefits are immense. Continued progress could enable more precise tools for predicting patient responses and the development of a new generation of therapeutics based on, or targeted at, the human microbiome.}, }
@article {pmid29556543, year = {2018}, author = {}, title = {Conflict of Interest Declarations by Contributing Editors of the Special Issue on Early-Career Systems Microbiology Scientists, Sponsored by Janssen Human Microbiome Institute (JHMI).}, journal = {mSystems}, volume = {3}, number = {2}, pages = {}, doi = {10.1128/mSystems.00010-18}, pmid = {29556543}, issn = {2379-5077}, }
@article {pmid29556541, year = {2018}, author = {Waldron, L}, title = {Data and Statistical Methods To Analyze the Human Microbiome.}, journal = {mSystems}, volume = {3}, number = {2}, pages = {}, pmid = {29556541}, issn = {2379-5077}, support = {R21 AI121784/AI/NIAID NIH HHS/United States ; U24 CA180996/CA/NCI NIH HHS/United States ; }, abstract = {The Waldron lab for computational biostatistics bridges the areas of cancer genomics and microbiome studies for public health, developing methods to exploit publicly available data resources and to integrate -omics studies.}, }
@article {pmid29556534, year = {2018}, author = {Segata, N}, title = {On the Road to Strain-Resolved Comparative Metagenomics.}, journal = {mSystems}, volume = {3}, number = {2}, pages = {}, pmid = {29556534}, issn = {2379-5077}, abstract = {Metagenomics has transformed microbiology, but its potential has not been fully expressed yet. From computational methods for digging deeper into metagenomes to study designs for addressing specific hypotheses, the Segata Lab is pursuing an integrative metagenomic approach to describe and model human-associated microbial communities as collections of strains. Linking strain variants to host phenotypes and performing cultivation-free population genomics require large cohorts and meta-analysis strategies to synthesize available cohorts but can revolutionize our understanding of the personalized host-microbiome interface which is at the base of human health.}, }
@article {pmid29554085, year = {2018}, author = {Douglas, AE}, title = {Which experimental systems should we use for human microbiome science?.}, journal = {PLoS biology}, volume = {16}, number = {3}, pages = {e2005245}, pmid = {29554085}, issn = {1545-7885}, support = {R01 GM095372/GM/NIGMS NIH HHS/United States ; }, mesh = {Humans ; *Microbiota ; *Models, Animal ; *Research Design ; }, abstract = {Microbiome science is revealing that the phenotype and health of animals, including humans, depend on the sustained function of their resident microorganisms. In this essay, I argue for thoughtful choice of model systems for human microbiome science. A greater variety of experimental systems, including wider use of invertebrate models, would benefit biomedical research, while systems ill-suited to experimental and genetic manipulation can be used to address very limited sets of scientific questions. Microbiome science benefits from the coordinated use of multiple systems, which is facilitated by networks of researchers with expertise in different experimental systems.}, }
@article {pmid29553575, year = {2018}, author = {Seshadri, R and Leahy, SC and Attwood, GT and Teh, KH and Lambie, SC and Cookson, AL and Eloe-Fadrosh, EA and Pavlopoulos, GA and Hadjithomas, M and Varghese, NJ and Paez-Espino, D and ,  and Perry, R and Henderson, G and Creevey, CJ and Terrapon, N and Lapebie, P and Drula, E and Lombard, V and Rubin, E and Kyrpides, NC and Henrissat, B and Woyke, T and Ivanova, NN and Kelly, WJ}, title = {Cultivation and sequencing of rumen microbiome members from the Hungate1000 Collection.}, journal = {Nature biotechnology}, volume = {36}, number = {4}, pages = {359-367}, pmid = {29553575}, issn = {1546-1696}, support = {322820/ERC_/European Research Council/International ; }, mesh = {Animals ; Archaea/classification/*genetics/metabolism ; Bacteria/classification/*genetics/metabolism ; Biofuels ; Gastrointestinal Microbiome/*genetics ; Humans ; Lignin/chemistry/genetics ; Microbiota/genetics ; Rumen/*microbiology ; }, abstract = {Productivity of ruminant livestock depends on the rumen microbiota, which ferment indigestible plant polysaccharides into nutrients used for growth. Understanding the functions carried out by the rumen microbiota is important for reducing greenhouse gas production by ruminants and for developing biofuels from lignocellulose. We present 410 cultured bacteria and archaea, together with their reference genomes, representing every cultivated rumen-associated archaeal and bacterial family. We evaluate polysaccharide degradation, short-chain fatty acid production and methanogenesis pathways, and assign specific taxa to functions. A total of 336 organisms were present in available rumen metagenomic data sets, and 134 were present in human gut microbiome data sets. Comparison with the human microbiome revealed rumen-specific enrichment for genes encoding de novo synthesis of vitamin B12, ongoing evolution by gene loss and potential vertical inheritance of the rumen microbiome based on underrepresentation of markers of environmental stress. We estimate that our Hungate genome resource represents ∼75% of the genus-level bacterial and archaeal taxa present in the rumen.}, }
@article {pmid29545777, year = {2018}, author = {Bochtler, M and Mizgalska, D and Veillard, F and Nowak, ML and Houston, J and Veith, P and Reynolds, EC and Potempa, J}, title = {The Bacteroidetes Q-Rule: Pyroglutamate in Signal Peptidase I Substrates.}, journal = {Frontiers in microbiology}, volume = {9}, number = {}, pages = {230}, pmid = {29545777}, issn = {1664-302X}, support = {R01 DE022597/DE/NIDCR NIH HHS/United States ; R21 DE026280/DE/NIDCR NIH HHS/United States ; }, abstract = {Bacteroidetes feature prominently in the human microbiome, as major colonizers of the gut and clinically relevant pathogens elsewhere. Here, we reveal a new Bacteroidetes specific feature in the otherwise widely conserved Sec/SPI (Sec translocase/signal peptidase I) pathway. In Bacteroidetes, but not the entire FCB group or related phyla, signal peptide cleavage exposes N-terminal glutamine residues in most SPI substrates. Reanalysis of published mass spectrometry data for five Bacteroidetes species shows that the newly exposed glutamines are cyclized to pyroglutamate (also termed 5-oxoproline) residues. Using the dental pathogen Porphyromonas gingivalis as a model, we identify the PG2157 (also called PG_RS09565, Q7MT37) as the glutaminyl cyclase in this species, and map the catalytic activity to the periplasmic face of the inner membrane. Genetic manipulations that alter the glutamine residue immediately after the signal peptide in the pre-pro-forms of the gingipains affect the extracellular proteolytic activity of RgpA, but not RgpB and Kgp. Glutamine statistics, mass spectrometry data and the mutagenesis results show that the N-terminal glutamine residues or their pyroglutamate cyclization products do not act as generic sorting signals.}, }
@article {pmid29535205, year = {2018}, author = {Jacobson, AN and Choudhury, BP and Fischbach, MA}, title = {The Biosynthesis of Lipooligosaccharide from Bacteroides thetaiotaomicron.}, journal = {mBio}, volume = {9}, number = {2}, pages = {}, pmid = {29535205}, issn = {2150-7511}, support = {DP1 DK113598/DK/NIDDK NIH HHS/United States ; R01 DK110174/DK/NIDDK NIH HHS/United States ; T32 GM064337/GM/NIGMS NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Bacteroides thetaiotaomicron/*genetics/*metabolism ; Biosynthetic Pathways/*genetics ; Lipopolysaccharides/*biosynthesis/chemistry ; Mutation ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization ; }, abstract = {Lipopolysaccharide (LPS), a cell-associated glycolipid that makes up the outer leaflet of the outer membrane of Gram-negative bacteria, is a canonical mediator of microbe-host interactions. The most prevalent Gram-negative gut bacterial taxon, Bacteroides, makes up around 50% of the cells in a typical Western gut; these cells harbor ~300 mg of LPS, making it one of the highest-abundance molecules in the intestine. As a starting point for understanding the biological function of Bacteroides LPS, we have identified genes in Bacteroides thetaiotaomicron VPI 5482 involved in the biosynthesis of its lipid A core and glycan, generated mutants that elaborate altered forms of LPS, and used matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry to interrogate the molecular features of these variants. We demonstrate, inter alia, that the glycan does not appear to have a repeating unit, and so this strain produces lipooligosaccharide (LOS) rather than LPS. This result contrasts with Bacteroides vulgatus ATCC 8482, which by SDS-PAGE analysis appears to produce LPS with a repeating unit. Additionally, our identification of the B. thetaiotaomicron LOS oligosaccharide gene cluster allowed us to identify similar clusters in other Bacteroides species. Our work lays the foundation for developing a structure-function relationship for Bacteroides LPS/LOS in the context of host colonization.IMPORTANCE Much is known about the bacterial species and genes that make up the human microbiome, but remarkably little is known about the molecular mechanisms through which the microbiota influences host biology. A well-known mechanism by which bacteria influence the host centers around lipopolysaccharide (LPS), a component of the Gram-negative bacterial outer membrane. Pathogen-derived LPS is a potent ligand for host receptor Toll-like receptor 4, which plays an important role in sensing bacteria as part of the innate immune response. Puzzlingly, the most common genus of human gut bacteria, Bacteroides, produces LPS but does not elicit a potent proinflammatory response. Previous work showing that Bacteroides LPS differs structurally from pathogen-derived LPS suggested the outlines of an explanation. Here, we take the next step, elucidating the biosynthetic pathway for Bacteroides LPS and generating mutants in the process that will be of great use in understanding how this molecule modulates the host immune response.}, }
@article {pmid29535201, year = {2018}, author = {Cross, KL and Chirania, P and Xiong, W and Beall, CJ and Elkins, JG and Giannone, RJ and Griffen, AL and Guss, AM and Hettich, RL and Joshi, SS and Mokrzan, EM and Martin, RK and Zhulin, IB and Leys, EJ and Podar, M}, title = {Insights into the Evolution of Host Association through the Isolation and Characterization of a Novel Human Periodontal Pathobiont, Desulfobulbus oralis.}, journal = {mBio}, volume = {9}, number = {2}, pages = {}, pmid = {29535201}, issn = {2150-7511}, support = {R01 DE024463/DE/NIDCR NIH HHS/United States ; }, mesh = {*Adaptation, Biological ; Deltaproteobacteria/*genetics/*isolation &amp; purification ; *Evolution, Molecular ; Gene Expression Profiling ; Gene Transfer, Horizontal ; *Genome, Bacterial ; Gingiva/*microbiology ; Humans ; Ohio ; Periodontitis/microbiology ; Phylogeny ; Proteome/analysis ; }, abstract = {The human oral microbiota encompasses representatives of many bacterial lineages that have not yet been cultured. Here we describe the isolation and characterization of previously uncultured Desulfobulbus oralis, the first human-associated representative of its genus. As mammalian-associated microbes rarely have free-living close relatives, D. oralis provides opportunities to study how bacteria adapt and evolve within a host. This sulfate-reducing deltaproteobacterium has adapted to the human oral subgingival niche by curtailing its physiological repertoire, losing some biosynthetic abilities and metabolic independence, and by dramatically reducing environmental sensing and signaling capabilities. The genes that enable free-living Desulfobulbus to synthesize the potent neurotoxin methylmercury were also lost by D. oralis, a notably positive outcome of host association. However, horizontal gene acquisitions from other members of the microbiota provided novel mechanisms of interaction with the human host, including toxins like leukotoxin and hemolysins. Proteomic and transcriptomic analysis revealed that most of those factors are actively expressed, including in the subgingival environment, and some are secreted. Similar to other known oral pathobionts, D. oralis can trigger a proinflammatory response in oral epithelial cells, suggesting a direct role in the development of periodontal disease.IMPORTANCE Animal-associated microbiota likely assembled as a result of numerous independent colonization events by free-living microbes followed by coevolution with their host and other microbes. Through specific adaptation to various body sites and physiological niches, microbes have a wide range of contributions, from beneficial to disease causing. Desulfobulbus oralis provides insights into genomic and physiological transformations associated with transition from an open environment to a host-dependent lifestyle and the emergence of pathogenicity. Through a multifaceted mechanism triggering a proinflammatory response, D. oralis is a novel periodontal pathobiont. Even though culture-independent approaches can provide insights into the potential role of the human microbiome "dark matter," cultivation and experimental characterization remain important to studying the roles of individual organisms in health and disease.}, }
@article {pmid29532031, year = {2018}, author = {Kim, HJ and Kim, H and Kim, JJ and Myeong, NR and Kim, T and Park, T and Kim, E and Choi, JY and Lee, J and An, S and Sul, WJ}, title = {Fragile skin microbiomes in megacities are assembled by a predominantly niche-based process.}, journal = {Science advances}, volume = {4}, number = {3}, pages = {e1701581}, pmid = {29532031}, issn = {2375-2548}, mesh = {Adult ; Asian People ; Bacteria/growth &amp; development ; Cities ; Female ; Humans ; *Microbiota ; Skin/*microbiology ; }, abstract = {Given the higher incidence of skin diseases in more urbanized populations and its association with the skin microbiome, we questioned how the skin microbiome differed depending on the degree of urbanization. Skin microbiomes of 231 healthy subjects in five large cities in China varied mainly with environment and socioeconomic status of the cities in question. The differences among microbiomes could be explained by the predominantly niche-based assembly of microbial communities, which was supported by a dominance test, β-null deviation, and edge-length abundance distribution. Networks among microbes in larger cities were more fragile, which may contribute to the higher incidence of skin diseases in more urbanized environments. These results suggest that microbial ecological theory can provide a framework for understanding crucial health-associated features of the human microbiome.}, }
@article {pmid29525681, year = {2018}, author = {Wang, X and Zhang, L and Wang, Y and Liu, X and Zhang, H and Liu, Y and Shen, N and Yang, J and Gai, Z}, title = {Gut microbiota dysbiosis is associated with Henoch-Schönlein Purpura in children.}, journal = {International immunopharmacology}, volume = {58}, number = {}, pages = {1-8}, doi = {10.1016/j.intimp.2018.03.003}, pmid = {29525681}, issn = {1878-1705}, mesh = {Adolescent ; Bacteroidaceae/*physiology ; Bifidobacterium/*physiology ; Child ; Child, Preschool ; Dysbiosis/*genetics/microbiology ; Enterococcus/*physiology ; Feces/microbiology ; Female ; Gastrointestinal Microbiome/*genetics ; High-Throughput Nucleotide Sequencing ; Humans ; IgA Vasculitis/genetics/*microbiology ; Male ; RNA, Ribosomal, 16S/*genetics ; }, abstract = {BACKGROUND: Alterations in the intestinal microbiota have been associated with the development of allergic diseases, such as asthma and food allergies. However, there is no report detailing the role of microbiota alterations in Henoch-Schönlein Purpura (HSP) development.<br><br>METHOD: A total of 85 children with HSP and 70 healthy children were recruited for this study. Intestinal microbiota composition was analyzed by 16S rRNA gene-based pyrosequencing. Fecal microbial diversity and composition were compared.<br><br>RESULT: We compared the gut microbiota of 155 subjects and found that children with HSP exhibited gut microbial dysbiosis. Lower microbial diversity and richness were found in HSP patients when compared to the control group. Based on an analysis of similarities, the composition of the microbiota in HSP patients was also different from that of the control group (r&#x202f;=&#x202f;0.306, P&#x202f;=&#x202f;0.001). The relative abundance of the bacterial genera Dialister (P&#x202f;<&#x202f;0.0001), Roseburia (P&#x202f;<&#x202f;0.0001), and Parasutterella (P&#x202f;<&#x202f;0.0001) was significantly decreased in HSP children, while the relative abundance of Parabacteroides (P&#x202f;<&#x202f;0.006) and Enterococcus (P&#x202f;<&#x202f;0.0001) in these children was significantly increased. Based on Spearman correlation analysis, the LOS showed a significant negative (P&#x202f;<&#x202f;0.05) correlation with the genera Paraprevotella and Roseburia. Meanwhile, IgA levels exhibited a significant negative (P&#x202f;<&#x202f;0.01) correlation with the genus Bifidobacterium.<br><br>CONCLUSIONS: Our results indicate that HSP is associated with significant compositional and structural changes in the gut microbiota. These results enhance the potential for future microbial-based therapies to improve the clinical outcome of HSP in children.}, }
@article {pmid29522743, year = {2018}, author = {Ferreiro, A and Crook, N and Gasparrini, AJ and Dantas, G}, title = {Multiscale Evolutionary Dynamics of Host-Associated Microbiomes.}, journal = {Cell}, volume = {172}, number = {6}, pages = {1216-1227}, pmid = {29522743}, issn = {1097-4172}, support = {R01 GM099538/GM/NIGMS NIH HHS/United States ; T32 DK077653/DK/NIDDK NIH HHS/United States ; R01 AI123394/AI/NIAID NIH HHS/United States ; R01 HD092414/HD/NICHD NIH HHS/United States ; U01 AI123394/AI/NIAID NIH HHS/United States ; T32 GM007067/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Ecosystem ; *Evolution, Molecular ; Gene Transfer, Horizontal ; *Genetic Variation ; Host Specificity ; Humans ; Metagenome/*genetics ; Microbiota/*genetics ; }, abstract = {The composite members of the microbiota face a range of selective pressures and must adapt to persist in the host. We highlight recent work characterizing the evolution and transfer of genetic information across nested scales of host-associated microbiota, which enable resilience to biotic and abiotic perturbations. At the strain level, we consider the preservation and diversification of adaptive information in progeny lineages. At the community level, we consider genetic exchange between distinct microbes in the ecosystem. Finally, we frame microbiomes as open systems subject to acquisition of novel information from foreign ecosystems through invasion by outsider microbes.}, }
@article {pmid29522739, year = {2018}, author = {Blaser, MJ}, title = {The Past and Future Biology of the Human Microbiome in an Age of Extinctions.}, journal = {Cell}, volume = {172}, number = {6}, pages = {1173-1177}, doi = {10.1016/j.cell.2018.02.040}, pmid = {29522739}, issn = {1097-4172}, support = {U01 AI122285/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Anti-Bacterial Agents/administration &amp; dosage ; Biology/*methods/trends ; Drug Resistance, Bacterial/genetics ; Gastrointestinal Tract/embryology/growth &amp; development/*microbiology ; Genetic Variation ; *Host Microbial Interactions ; Humans ; Metagenome/*genetics ; Microbiota/*physiology ; }, abstract = {The evolutionary fate of humans is intimately linked with that of our microbiome. Medical and technological advances have caused large-scale changes in the composition and maturation of human-associated microbial communities, increasing our susceptibility to infectious and developmental diseases. Restoration of the human microbiome must become a priority for biomedicine.}, }
@article {pmid29518346, year = {2018}, author = {Solbiati, J and Frias-Lopez, J}, title = {Metatranscriptome of the Oral Microbiome in Health and Disease.}, journal = {Journal of dental research}, volume = {97}, number = {5}, pages = {492-500}, pmid = {29518346}, issn = {1544-0591}, support = {R01 DE021553/DE/NIDCR NIH HHS/United States ; }, mesh = {Chronic Periodontitis/microbiology ; Dental Caries/microbiology ; Dental Plaque/microbiology ; Gene Expression Profiling ; Humans ; Microbiota/*genetics ; Mouth/*microbiology ; Mouth Diseases/*microbiology ; *Transcriptome ; }, abstract = {The last few decades have witnessed an increasing interest in studying the human microbiome and its role in health and disease. The focus of those studies was mainly the characterization of changes in the composition of the microbial communities under different conditions. As a result of those studies, we now know that imbalance in the composition of the microbiome, also referred to as microbial dysbiosis, is directly linked to developing certain conditions. Dysbiosis of the oral microbiome is a prime example of how this imbalance leads to disease in the case of periodontal disease. However, there is considerable overlap in the phylogenetic profiles of microbial communities associated with active and inactive lesions, suggesting that the difference in periodontal status of those sites may not be explained solely by differences in the subgingival microbial composition. These findings suggest that differences in functional activities may be the essential elements that define the dysbiotic process. Researchers have recently begun to study gene expression of the oral microbiome in situ with the goal of identifying changes in functional activities that could explain the transition from health to disease. These initial results suggest that, rather than a specific composition, a better understanding of oral dysbiosis can be obtained from the study of functional activities of the microbial community. In this review, we give a summary of these initial studies, which have opened a new door to our understanding of the dynamics of the oral community during the dysbiotic process in the oral cavity.}, }
@article {pmid29507896, year = {2018}, author = {Stagaman, K and Cepon-Robins, TJ and Liebert, MA and Gildner, TE and Urlacher, SS and Madimenos, FC and Guillemin, K and Snodgrass, JJ and Sugiyama, LS and Bohannan, BJM}, title = {Market Integration Predicts Human Gut Microbiome Attributes across a Gradient of Economic Development.}, journal = {mSystems}, volume = {3}, number = {1}, pages = {}, pmid = {29507896}, issn = {2379-5077}, support = {P50 GM098911/GM/NIGMS NIH HHS/United States ; T32 GM007413/GM/NIGMS NIH HHS/United States ; }, abstract = {Economic development is marked by dramatic increases in the incidence of microbiome-associated diseases, such as autoimmune diseases and metabolic syndromes, but the lifestyle changes that drive alterations in the human microbiome are not known. We measured market integration as a proxy for economically related lifestyle attributes, such as ownership of specific market goods that index degree of market integration and components of traditional and nontraditional (more modern) house structure and infrastructure, and profiled the fecal microbiomes of 213 participants from a contiguous, indigenous Ecuadorian population. Despite relatively modest differences in lifestyle across the population, greater economic development correlated with significantly lower within-host diversity, higher between-host dissimilarity, and a decrease in the relative abundance of the bacterium Prevotella. These microbiome shifts were most strongly associated with more modern housing, followed by reduced ownership of traditional subsistence lifestyle-associated items. IMPORTANCE Previous research has reported differences in the gut microbiome between populations residing in wealthy versus poorer countries, leading to the assertion that lifestyle changes associated with economic development promote changes in the gut microbiome that promote the proliferation of microbiome-associated diseases. However, a direct relationship between economic development and the gut microbiome has not previously been shown. We surveyed the gut microbiomes of a single indigenous population undergoing economic development and found significant associations between features of the gut microbiome and lifestyle changes associated with economic development. These findings suggest that even the earliest stages of economic development can drive changes in the gut microbiome, which may provide a warning sign for the development of microbiome-associated diseases.}, }
@article {pmid29492330, year = {2017}, author = {Lang, JM and Coil, DA and Neches, RY and Brown, WE and Cavalier, D and Severance, M and Hampton-Marcell, JT and Gilbert, JA and Eisen, JA}, title = {A microbial survey of the International Space Station (ISS).}, journal = {PeerJ}, volume = {5}, number = {}, pages = {e4029}, pmid = {29492330}, issn = {2167-8359}, abstract = {BACKGROUND: Modern advances in sequencing technology have enabled the census of microbial members of many natural ecosystems. Recently, attention is increasingly being paid to the microbial residents of human-made, built ecosystems, both private (homes) and public (subways, office buildings, and hospitals). Here, we report results of the characterization of the microbial ecology of a singular built environment, the International Space Station (ISS). This ISS sampling involved the collection and microbial analysis (via 16S rDNA PCR) of 15 surfaces sampled by swabs onboard the ISS. This sampling was a component of Project MERCCURI (Microbial Ecology Research Combining Citizen and University Researchers on ISS). Learning more about the microbial inhabitants of the "buildings" in which we travel through space will take on increasing importance, as plans for human exploration continue, with the possibility of colonization of other planets and moons.<br><br>RESULTS: Sterile swabs were used to sample 15 surfaces onboard the ISS. The sites sampled were designed to be analogous to samples collected for (1) the Wildlife of Our Homes project and (2) a study of cell phones and shoes that were concurrently being collected for another component of Project MERCCURI. Sequencing of the 16S rDNA genes amplified from DNA extracted from each swab was used to produce a census of the microbes present on each surface sampled. We compared the microbes found on the ISS swabs to those from both homes on Earth and data from the Human Microbiome Project.<br><br>CONCLUSIONS: While significantly different from homes on Earth and the Human Microbiome Project samples analyzed here, the microbial community composition on the ISS was more similar to home surfaces than to the human microbiome samples. The ISS surfaces are species-rich with 1,036-4,294 operational taxonomic units (OTUs per sample). There was no discernible biogeography of microbes on the 15 ISS surfaces, although this may be a reflection of the small sample size we were able to obtain.}, }
@article {pmid29490879, year = {2019}, author = {Wu, WK and Chen, CC and Panyod, S and Chen, RA and Wu, MS and Sheen, LY and Chang, SC}, title = {Optimization of fecal sample processing for microbiome study - The journey from bathroom to bench.}, journal = {Journal of the Formosan Medical Association = Taiwan yi zhi}, volume = {118}, number = {2}, pages = {545-555}, doi = {10.1016/j.jfma.2018.02.005}, pmid = {29490879}, issn = {0929-6646}, mesh = {DNA/*isolation &amp; purification ; Feces/*microbiology ; *Gastrointestinal Microbiome ; Humans ; Metagenomics ; Reagent Kits, Diagnostic ; Sequence Analysis, DNA ; Specimen Handling/*methods/*standards ; }, abstract = {Although great interest has been displayed by researchers in the contribution of gut microbiota to human health, there is still no standard protocol with consensus to guarantee the sample quality of metagenomic analysis. Here we reviewed existing methodology studies and present suggestions for optimizing research pipeline from fecal sample collection to DNA extraction. First, we discuss strategies of clinical metadata collection as common confounders for microbiome research. Second, we propose general principles for freshly collected fecal sample and its storage and share a DIY stool collection kit protocol based on the manual procedure of Human Microbiome Project (HMP). Third, we provide a useful information of collection kit with DNA stabilization buffers and compare their pros and cons for multi-omic study. Fourth, we offer technical strategies as well as information of novel tools for sample aliquoting before long-term storage. Fifth, we discuss the substantial impact of different DNA extraction protocols on technical variations of metagenomic analysis. And lastly, we point out the limitation of current methods and the unmet needs for better quality control of metagenomic analysis. We hope the information provided here will help investigators in this exciting field to advance their studies while avoiding experimental artifacts.}, }
@article {pmid29488821, year = {2018}, author = {Hakansson, AP and Orihuela, CJ and Bogaert, D}, title = {Bacterial-Host Interactions: Physiology and Pathophysiology of Respiratory Infection.}, journal = {Physiological reviews}, volume = {98}, number = {2}, pages = {781-811}, pmid = {29488821}, issn = {1522-1210}, support = {SCAF/16/03/CSO_/Chief Scientist Office/United Kingdom ; SCAD/16/03/CSO_/Chief Scientist Office/United Kingdom ; R01 AI114800/AI/NIAID NIH HHS/United States ; R21 AI121614/AI/NIAID NIH HHS/United States ; R21 AI117309/AI/NIAID NIH HHS/United States ; R21 AG055144/AG/NIA NIH HHS/United States ; }, mesh = {Animals ; Bacteria ; Host-Pathogen Interactions/*immunology ; Humans ; Inflammation/*immunology ; Microbiota/*physiology ; Respiratory Tract Infections/*microbiology/physiopathology ; Symbiosis/physiology ; }, abstract = {It has long been thought that respiratory infections are the direct result of acquisition of pathogenic viruses or bacteria, followed by their overgrowth, dissemination, and in some instances tissue invasion. In the last decades, it has become apparent that in contrast to this classical view, the majority of microorganisms associated with respiratory infections and inflammation are actually common members of the respiratory ecosystem and only in rare circumstances do they cause disease. This suggests that a complex interplay between host, environment, and properties of colonizing microorganisms together determines disease development and its severity. To understand the pathophysiological processes that underlie respiratory infectious diseases, it is therefore necessary to understand the host-bacterial interactions occurring at mucosal surfaces, along with the microbes inhabiting them, during symbiosis. Current knowledge regarding host-bacterial interactions during asymptomatic colonization will be discussed, including a plausible role for the human microbiome in maintaining a healthy state. With this as a starting point, we will discuss possible disruptive factors contributing to dysbiosis, which is likely to be a key trigger for pathobionts in the development and pathophysiology of respiratory diseases. Finally, from this renewed perspective, we will reflect on current and potential new approaches for treatment in the future.}, }
@article {pmid29475860, year = {2018}, author = {Daisley, BA and Trinder, M and McDowell, TW and Collins, SL and Sumarah, MW and Reid, G}, title = {Microbiota-Mediated Modulation of Organophosphate Insecticide Toxicity by Species-Dependent Interactions with Lactobacilli in a Drosophila melanogaster Insect Model.}, journal = {Applied and environmental microbiology}, volume = {84}, number = {9}, pages = {}, pmid = {29475860}, issn = {1098-5336}, mesh = {Animals ; Bacteria/*metabolism ; Chlorpyrifos/metabolism/*toxicity ; Drosophila melanogaster/*drug effects/microbiology ; Insecticides/metabolism/*toxicity ; Lactobacillus/*metabolism ; *Microbiota ; Models, Animal ; Probiotics ; Species Specificity ; }, abstract = {Despite the benefits to the global food supply and agricultural economies, pesticides are believed to pose a threat to the health of both humans and wildlife. Chlorpyrifos (CP), a commonly used organophosphate insecticide, has poor target specificity and causes acute neurotoxicity in a wide range of species via the suppression of acetylcholinesterase. This effect is exacerbated 10- to 100-fold by chlorpyrifos oxon (CPO), a principal metabolite of CP. Since many animal-associated symbiont microorganisms are known to hydrolyze CP into CPO, we used a Drosophila melanogaster insect model to investigate the hypothesis that indigenous and probiotic bacteria could affect CP metabolism and toxicity. Antibiotic-treated and germfree D. melanogaster insects lived significantly longer than their conventionally reared counterparts when exposed to 10 μM CP. Drosophila melanogaster gut-derived Lactobacillus plantarum, but not Acetobacterindonesiensis, was shown to metabolize CP. Liquid chromatography tandem-mass spectrometry confirmed that the L. plantarum isolate preferentially metabolized CP into CPO when grown in CP-spiked culture medium. Further experiments showed that monoassociating germfree D. melanogaster with the L. plantarum isolate could reestablish a conventional-like sensitivity to CP. Interestingly, supplementation with the human probiotic Lactobacillus rhamnosus GG (a strain that binds but does not metabolize CP) significantly increased the survival of the CP-exposed germfree D. melanogaster This suggests strain-specific differences in CP metabolism may exist among lactobacilli and emphasizes the need for further investigation. In summary, these results suggest that (i) CPO formation by the gut microbiota can have biologically relevant consequences for the host, and (ii) probiotic lactobacilli may be beneficial in reducing in vivo CP toxicity.IMPORTANCE An understudied area of research is how the microbiota (microorganisms living in/on an animal) affects the metabolism and toxic outcomes of environmental pollutants such as pesticides. This study focused specifically on how the microbial biotransformation of chlorpyrifos (CP; a common organophosphate insecticide) affected host exposure and toxicity parameters in a Drosophila melanogaster insect model. Our results demonstrate that the biotransformation of CP by the gut microbiota had biologically relevant and toxic consequences on host health and that certain probiotic lactobacilli may be beneficial in reducing CP toxicity. Since inadvertent pesticide exposure is suspected to negatively impact the health of off-target species, these findings may provide useful information for wildlife conservation and environmental sustainability planning. Furthermore, the results highlight the need to consider microbiota composition differences between beneficial and pest insects in future insecticide designs. More broadly, this study supports the use of beneficial microorganisms to modulate the microbiota-mediated biotransformation of xenobiotics.}, }
@article {pmid29471863, year = {2018}, author = {Petrosino, JF}, title = {The microbiome in precision medicine: the way forward.}, journal = {Genome medicine}, volume = {10}, number = {1}, pages = {12}, pmid = {29471863}, issn = {1756-994X}, support = {HHSN267200700014C/LM/NLM NIH HHS/United States ; R01 AI108588/AI/NIAID NIH HHS/United States ; P30 DK056338/DK/NIDDK NIH HHS/United States ; R01 MH112356/MH/NIMH NIH HHS/United States ; U19 AI116497/AI/NIAID NIH HHS/United States ; }, mesh = {Disease ; Humans ; *Microbiota ; Phenotype ; *Precision Medicine ; }, abstract = {Novel associations between the human microbiome and health and disease are routinely emerging, and important host-microbiome interactions are targets for new diagnostics and therapeutics. Understanding how broadly host-microbe associations are maintained across populations is revealing individualized host-microbiome phenotypes that can be integrated with other 'omics' data sets to enhance precision medicine.}, }
@article {pmid29467286, year = {2018}, author = {Altindis, E and Cai, W and Sakaguchi, M and Zhang, F and GuoXiao, W and Liu, F and De Meyts, P and Gelfanov, V and Pan, H and DiMarchi, R and Kahn, CR}, title = {Viral insulin-like peptides activate human insulin and IGF-1 receptor signaling: A paradigm shift for host-microbe interactions.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {10}, pages = {2461-2466}, pmid = {29467286}, issn = {1091-6490}, support = {P30 DK036836/DK/NIDDK NIH HHS/United States ; R01 DK031036/DK/NIDDK NIH HHS/United States ; R01 DK033201/DK/NIDDK NIH HHS/United States ; R37 DK031036/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Cell Line ; Cell Proliferation ; Glucose/metabolism ; Hepatocytes ; Host-Pathogen Interactions/*physiology ; Humans ; Insulin/genetics/*metabolism ; Insulin-Like Growth Factor I/*metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Receptor, IGF Type 1/*metabolism ; Signal Transduction ; Viral Proteins/genetics/*metabolism ; Virus Diseases/virology ; Viruses/*genetics ; }, abstract = {Viruses are the most abundant biological entities and carry a wide variety of genetic material, including the ability to encode host-like proteins. Here we show that viruses carry sequences with significant homology to several human peptide hormones including insulin, insulin-like growth factors (IGF)-1 and -2, FGF-19 and -21, endothelin-1, inhibin, adiponectin, and resistin. Among the strongest homologies were those for four viral insulin/IGF-1-like peptides (VILPs), each encoded by a different member of the family Iridoviridae VILPs show up to 50% homology to human insulin/IGF-1, contain all critical cysteine residues, and are predicted to form similar 3D structures. Chemically synthesized VILPs can bind to human and murine IGF-1/insulin receptors and stimulate receptor autophosphorylation and downstream signaling. VILPs can also increase glucose uptake in adipocytes and stimulate the proliferation of fibroblasts, and injection of VILPs into mice significantly lowers blood glucose. Transfection of mouse hepatocytes with DNA encoding a VILP also stimulates insulin/IGF-1 signaling and DNA synthesis. Human microbiome studies reveal the presence of these Iridoviridae in blood and fecal samples. Thus, VILPs are members of the insulin/IGF superfamily with the ability to be active on human and rodent cells, raising the possibility for a potential role of VILPs in human disease. Furthermore, since only 2% of viruses have been sequenced, this study raises the potential for discovery of other viral hormones which, along with known virally encoded growth factors, may modify human health and disease.}, }
@article {pmid29453029, year = {2018}, author = {Peñalver Bernabé, B and Cralle, L and Gilbert, JA}, title = {Systems biology of the human microbiome.}, journal = {Current opinion in biotechnology}, volume = {51}, number = {}, pages = {146-153}, doi = {10.1016/j.copbio.2018.01.018}, pmid = {29453029}, issn = {1879-0429}, mesh = {Bacteria/*classification/metabolism ; Humans ; *Metabolome ; *Microbiota ; *Precision Medicine ; Systems Biology/*methods ; }, abstract = {Recent research has shown that the microbiome-a collection of microorganisms, including bacteria, fungi, and viruses, living on and in a host-are of extraordinary importance in human health, even from conception and development in the uterus. Therefore, to further our ability to diagnose disease, to predict treatment outcomes, and to identify novel therapeutics, it is essential to include microbiome and microbial metabolic biomarkers in Systems Biology investigations. In clinical studies or, more precisely, Systems Medicine approaches, we can use the diversity and individual characteristics of the personal microbiome to enhance our resolution for patient stratification. In this review, we explore several Systems Medicine approaches, including Microbiome Wide Association Studies to understand the role of the human microbiome in health and disease, with a focus on 'preventive medicine' or P4 (i.e., personalized, predictive, preventive, participatory) medicine.}, }
@article {pmid29447696, year = {2018}, author = {Smillie, CS and Sauk, J and Gevers, D and Friedman, J and Sung, J and Youngster, I and Hohmann, EL and Staley, C and Khoruts, A and Sadowsky, MJ and Allegretti, JR and Smith, MB and Xavier, RJ and Alm, EJ}, title = {Strain Tracking Reveals the Determinants of Bacterial Engraftment in the Human Gut Following Fecal Microbiota Transplantation.}, journal = {Cell host &amp; microbe}, volume = {23}, number = {2}, pages = {229-240.e5}, pmid = {29447696}, issn = {1934-6069}, support = {P30 DK043351/DK/NIDDK NIH HHS/United States ; R01 AT009708/AT/NCCIH NIH HHS/United States ; R01 DK092405/DK/NIDDK NIH HHS/United States ; T32 GM087237/GM/NIGMS NIH HHS/United States ; }, mesh = {Biodiversity ; Clostridioides difficile/*growth &amp; development ; Clostridium Infections/*prevention &amp; control/therapy ; Fecal Microbiota Transplantation/*methods ; Gastrointestinal Microbiome/*physiology ; Gastrointestinal Tract/*microbiology ; Humans ; Models, Biological ; Recurrence ; Secondary Prevention/*methods ; }, abstract = {Fecal microbiota transplantation (FMT) from healthy donor to patient is a treatment for microbiome-associated diseases. Although the success of FMT requires donor bacteria to engraft in the patient's gut, the forces governing engraftment in humans are unknown. Here we use an ongoing clinical experiment, the treatment of recurrent Clostridium difficile infection, to uncover the rules of engraftment in humans. We built a statistical model that predicts which bacterial species will engraft in a given host, and developed Strain Finder, a method to infer strain genotypes and track them over time. We find that engraftment can be predicted largely from the abundance and phylogeny of bacteria in the donor and the pre-FMT patient. Furthermore, donor strains within a species engraft in an all-or-nothing manner and previously undetected strains frequently colonize patients receiving FMT. We validated these findings for metabolic syndrome, suggesting that the same principles of engraftment extend to other indications.}, }
@article {pmid29447068, year = {2018}, author = {Diop, K and Diop, A and Levasseur, A and Mediannikov, O and Robert, C and Armstrong, N and Couderc, C and Bretelle, F and Raoult, D and Fournier, PE and Fenollar, F}, title = {Microbial Culturomics Broadens Human Vaginal Flora Diversity: Genome Sequence and Description of Prevotella lascolaii sp. nov. Isolated from a Patient with Bacterial Vaginosis.}, journal = {Omics : a journal of integrative biology}, volume = {22}, number = {3}, pages = {210-222}, doi = {10.1089/omi.2017.0151}, pmid = {29447068}, issn = {1557-8100}, mesh = {Adult ; Anti-Bacterial Agents/pharmacology ; Bacteroidaceae Infections/*microbiology ; *Biodiversity ; Drug Resistance, Bacterial ; Female ; Genome, Bacterial ; Genomics/methods ; Humans ; Phenotype ; Phylogeny ; Prevotella/*classification/drug effects/*genetics ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization ; Vagina/microbiology ; Vaginosis, Bacterial/*microbiology ; }, abstract = {Microbial culturomics is a new subfield of postgenomic medicine and omics biotechnology application that has broadened our awareness on bacterial diversity of the human microbiome, including the human vaginal flora bacterial diversity. Using culturomics, a new obligate anaerobic Gram-stain-negative rod-shaped bacterium designated strain khD1[T] was isolated in the vagina of a patient with bacterial vaginosis and characterized using taxonogenomics. The most abundant cellular fatty acids were C15:0 anteiso (36%), C16:0 (19%), and C15:0 iso (10%). Based on an analysis of the full-length 16S rRNA gene sequences, phylogenetic analysis showed that the strain khD1[T] exhibited 90% sequence similarity with Prevotella loescheii, the phylogenetically closest validated Prevotella species. With 3,763,057 bp length, the genome of strain khD1[T] contained (mol%) 48.7 G + C and 3248 predicted genes, including 3194 protein-coding and 54 RNA genes. Given the phenotypical and biochemical characteristic results as well as genome sequencing, strain khD1[T] is considered to represent a novel species within the genus Prevotella, for which the name Prevotella lascolaii sp. nov. is proposed. The type strain is khD1[T] (= CSUR P0109, = DSM 101754). These results show that microbial culturomics greatly improves the characterization of the human microbiome repertoire by isolating potential putative new species. Further studies will certainly clarify the microbial mechanisms of pathogenesis of these new microbes and their role in health and disease. Microbial culturomics is an important new addition to the diagnostic medicine toolbox and warrants attention in future medical, global health, and integrative biology postgraduate teaching curricula.}, }
@article {pmid29444477, year = {2018}, author = {Simões-Silva, L and Araujo, R and Pestana, M and Soares-Silva, I and Sampaio-Maia, B}, title = {The microbiome in chronic kidney disease patients undergoing hemodialysis and peritoneal dialysis.}, journal = {Pharmacological research}, volume = {130}, number = {}, pages = {143-151}, doi = {10.1016/j.phrs.2018.02.011}, pmid = {29444477}, issn = {1096-1186}, mesh = {Animals ; Dietary Supplements ; Humans ; *Microbiota ; *Renal Dialysis ; Renal Insufficiency, Chronic/*microbiology/*therapy ; }, abstract = {Chronic kidney disease (CKD) is associated with an imbalanced human microbiome due not only to CKD-associated factors such as uremia, increased inflammation and immunosuppression, but also to pharmacological therapies and dietary restrictions. End-stage renal disease patients require renal replacement therapies commonly in the form of hemodialysis (HD) or peritoneal dialysis (PD). HD implies the existence of a vascular access, such as an arteriovenous fistula/graft or a venous catheter, whereas PD implies a long-term peritoneal catheter and the constant inflow of peritoneal dialysate. Also, dietary adaptations are mandatory in both therapies. This revision explores the impact of HD or PD therapies on human microbiome. HD and PD appear to be associated with different changes in the gut microbiome, for example a decrease in Proteobacteria relative abundance in HD patients and increase in PD patients. Both therapies may also have an impact on the human microbiome beyond the gut, leading to increased relative abundance of specific bacteria in the blood microbiome of HD patients and increased relative abundance of other bacteria in the peritoneal microbiome of PD patients. HD and PD catheter biofilms may also play an important role in the changes observed in these microbiomes. A more interdisciplinary approach is needed to further clarify the role of microbial groups other than bacteria in all body habitats to allow the complete understanding of the impact of HD or PD on the microbiome of CKD patients. Moreover, strategies that promote a healthy balance of the human microbiome on these patients should be explored.}, }
@article {pmid29444186, year = {2018}, author = {Donovan, PD and Gonzalez, G and Higgins, DG and Butler, G and Ito, K}, title = {Identification of fungi in shotgun metagenomics datasets.}, journal = {PloS one}, volume = {13}, number = {2}, pages = {e0192898}, pmid = {29444186}, issn = {1932-6203}, support = {/WT_/Wellcome Trust/United Kingdom ; }, mesh = {Animals ; Antarctic Regions ; Ascomycota/classification/genetics/isolation &amp; purification ; Candida tropicalis/genetics/pathogenicity ; Databases, Genetic ; Fungi/classification/*genetics/pathogenicity ; Humans ; Metagenome ; *Metagenomics ; Mice ; Microbiota/genetics ; Phylogeny ; Soil Microbiology ; Swine ; Zoonoses/microbiology ; }, abstract = {Metagenomics uses nucleic acid sequencing to characterize species diversity in different niches such as environmental biomes or the human microbiome. Most studies have used 16S rRNA amplicon sequencing to identify bacteria. However, the decreasing cost of sequencing has resulted in a gradual shift away from amplicon analyses and towards shotgun metagenomic sequencing. Shotgun metagenomic data can be used to identify a wide range of species, but have rarely been applied to fungal identification. Here, we develop a sequence classification pipeline, FindFungi, and use it to identify fungal sequences in public metagenome datasets. We focus primarily on animal metagenomes, especially those from pig and mouse microbiomes. We identified fungi in 39 of 70 datasets comprising 71 fungal species. At least 11 pathogenic species with zoonotic potential were identified, including Candida tropicalis. We identified Pseudogymnoascus species from 13 Antarctic soil samples initially analyzed for the presence of bacteria capable of degrading diesel oil. We also show that Candida tropicalis and Candida loboi are likely the same species. In addition, we identify several examples where contaminating DNA was erroneously included in fungal genome assemblies.}, }
@article {pmid29440648, year = {2018}, author = {Stokholm, J and Blaser, MJ and Thorsen, J and Rasmussen, MA and Waage, J and Vinding, RK and Schoos, AM and Kunøe, A and Fink, NR and Chawes, BL and Bønnelykke, K and Brejnrod, AD and Mortensen, MS and Al-Soud, WA and Sørensen, SJ and Bisgaard, H}, title = {Publisher Correction: Maturation of the gut microbiome and risk of asthma in childhood.}, journal = {Nature communications}, volume = {9}, number = {1}, pages = {704}, doi = {10.1038/s41467-018-03150-x}, pmid = {29440648}, issn = {2041-1723}, abstract = {The originally published version of this Article contained an incorrect version of Figure 3 that was introduced following peer review and inadvertently not corrected during the production process. Both versions contain the same set of abundance data, but the incorrect version has the children's asthma status erroneously disconnected from the abundance data, thereby producing the non-representative p values and graphic presentations. These errors have now been rectified, with the correct version of Figure 3 replaced in both the PDF and HTML versions of the Article.}, }
@article {pmid29430070, year = {2017}, author = {Ren, B and Bacallado, S and Favaro, S and Holmes, S and Trippa, L}, title = {Bayesian Nonparametric Ordination for the Analysis of Microbial Communities.}, journal = {Journal of the American Statistical Association}, volume = {112}, number = {520}, pages = {1430-1442}, pmid = {29430070}, issn = {0162-1459}, support = {R01 AI112401/AI/NIAID NIH HHS/United States ; DMS-1042785//National Science Foundation/International ; }, abstract = {Human microbiome studies use sequencing technologies to measure the abundance of bacterial species or Operational Taxonomic Units (OTUs) in samples of biological material. Typically the data are organized in contingency tables with OTU counts across heterogeneous biological samples. In the microbial ecology community, ordination methods are frequently used to investigate latent factors or clusters that capture and describe variations of OTU counts across biological samples. It remains important to evaluate how uncertainty in estimates of each biological sample's microbial distribution propagates to ordination analyses, including visualization of clusters and projections of biological samples on low dimensional spaces. We propose a Bayesian analysis for dependent distributions to endow frequently used ordinations with estimates of uncertainty. A Bayesian nonparametric prior for dependent normalized random measures is constructed, which is marginally equivalent to the normalized generalized Gamma process, a well-known prior for nonparametric analyses. In our prior, the dependence and similarity between microbial distributions is represented by latent factors that concentrate in a low dimensional space. We use a shrinkage prior to tune the dimensionality of the latent factors. The resulting posterior samples of model parameters can be used to evaluate uncertainty in analyses routinely applied in microbiome studies. Specifically, by combining them with multivariate data analysis techniques we can visualize credible regions in ecological ordination plots. The characteristics of the proposed model are illustrated through a simulation study and applications in two microbiome datasets.}, }
@article {pmid29425888, year = {2018}, author = {Rajpoot, M and Sharma, AK and Sharma, A and Gupta, GK}, title = {Understanding the microbiome: Emerging biomarkers for exploiting the microbiota for personalized medicine against cancer.}, journal = {Seminars in cancer biology}, volume = {52}, number = {Pt 1}, pages = {1-8}, doi = {10.1016/j.semcancer.2018.02.003}, pmid = {29425888}, issn = {1096-3650}, mesh = {*Biomarkers, Tumor ; Genetic Variation ; Humans ; Metagenomics/methods/trends ; Microbiota/*genetics ; Neoplasms/*diagnosis/*microbiology ; Precision Medicine/*methods/trends ; Sequence Analysis, DNA/methods ; }, abstract = {The human body is a home to more than 1 trillion microbes with a diverse variety of commensal microbes that play a crucial role towards the health of the individual. These microbes occupy different habitats such as gut, skin, vagina, oral etc. Not only the types and abundance of microbes are different in different organs, but also these may differ in different individuals. The genome of these microbiota and their ecosystem constitute to form a microbiome. Factors such as diet, environment, host genetics etc. may be the reason behind the wide microbial diversity. A number of studies performed on human microbiome have revealed that microbiota present in healthy and diseased individuals are distinct. Altered microbiome is many a times the reason behind the overexpression of genes which may cause complex diseases including cancer. Manipulation of the human microbiome can be done by microbial supplements such as probiotics or synbiotics, diet or prebiotics and microbial suppression strategies using antibiotics. Recent advances in genome sequencing technologies and metagenomic analysis provide us the broader understanding of these commensal microbes and highlighting the distinctive features of microbiome during healthy and disease states. Molecular pathological epidemiology (MPE) studies have been very helpful in providing insights into the pathological process behind disease evolution and progression by determining the specific etiological factors. New emerging field of research targets the microbiome for therapeutic purposes by which personalized medicines can be made for treating various types of tumors. Screening programmes might be helpful in identifying patients who are at the verge of developing cancer and in delivering appropriate approaches according to individual risk modes so that disease could be prevented.}, }
@article {pmid29416567, year = {2018}, author = {Liang, D and Leung, RK and Guan, W and Au, WW}, title = {Involvement of gut microbiome in human health and disease: brief overview, knowledge gaps and research opportunities.}, journal = {Gut pathogens}, volume = {10}, number = {}, pages = {3}, pmid = {29416567}, issn = {1757-4749}, abstract = {The commensal, symbiotic, and pathogenic microbial community which resides inside our body and on our skin (the human microbiome) can perturb host energy metabolism and immunity, and thus significantly influence development of a variety of human diseases. Therefore, the field has attracted unprecedented attention in the last decade. Although a large amount of data has been generated, there are still many unanswered questions and no universal agreements on how microbiome affects human health have been agreed upon. Consequently, this review was written to provide an updated overview of the rapidly expanding field, with a focus on revealing knowledge gaps and research opportunities. Specifically, the review covered animal physiology, optimal microbiome standard, health intervention by manipulating microbiome, knowledge base building by text mining, microbiota community structure and its implications in human diseases and health monitoring by analyzing microbiome in the blood. The review should enhance interest in conducting novel microbiota investigations that will further improve health and therapy.}, }
@article {pmid29413172, year = {2018}, author = {Krittanawong, C}, title = {Big Data Analytics, the Microbiome, Host-omic and Bug-omic Data and Risk for Cardiovascular Disease.}, journal = {Heart, lung &amp; circulation}, volume = {27}, number = {3}, pages = {e26-e27}, doi = {10.1016/j.hlc.2017.07.012}, pmid = {29413172}, issn = {1444-2892}, mesh = {Cardiovascular Diseases/*epidemiology ; Databases, Factual ; Global Health ; Humans ; *Microbiota ; Morbidity/trends ; Risk Assessment/*statistics &amp; numerical data ; Risk Factors ; }, }
@article {pmid29392389, year = {2018}, author = {Reen, FJ and Gutiérrez-Barranquero, JA and Parages, ML and O Gara, F}, title = {Coumarin: a novel player in microbial quorum sensing and biofilm formation inhibition.}, journal = {Applied microbiology and biotechnology}, volume = {102}, number = {5}, pages = {2063-2073}, pmid = {29392389}, issn = {1432-0614}, support = {FP7-PEOPLE-2013-ITN, 607786; FP7-KBBE-2012-6, CP-TP-312184; FP7-KBBE-2012-6, 311975; OCEAN 2011-2, 287589; Marie Curie 256596; EU-634486//European Commission/ ; SSPC-2, 12/RC/2275; 13/TIDA/B2625; 12/TIDA/B2411; 12/TIDA/B2405; 14/TIDA/2438, 15/TIDA/2977//Science Foundation Ireland/Ireland ; FIRM/RSF/CoFoRD; FIRM 08/RDC/629; FIRM 1/F009/MabS; FIRM 13/F/516//Department of Agriculture, Food and the Marine/ ; PD/2011/2414; GOIPG/2014/647//Irish Research Council for Science, Engineering and Technology/ ; MRCG-2014-6//Health Research Board/Ireland ; Beaufort award C2CRA 2007/082//Marine Institute/ ; Walsh Fellowship 2013//Teagasc/ ; CF-2017-0757-P//Enterprise Ireland/ ; }, mesh = {Animals ; Anti-Bacterial Agents/*pharmacology ; Bacteria/*drug effects ; Bacterial Infections/drug therapy/*microbiology ; Bacterial Physiological Phenomena/drug effects ; Biofilms/*drug effects ; Coumarins/*pharmacology ; Humans ; Quorum Sensing/*drug effects ; }, abstract = {Antibiotic resistance is a growing threat worldwide, causing serious problems in the treatment of microbial infections. The discovery and development of new drugs is urgently needed to overcome this problem which has greatly undermined the clinical effectiveness of conventional antibiotics. An intricate cell-cell communication system termed quorum sensing (QS) and the coordinated multicellular behaviour of biofilm formation have both been identified as promising targets for the treatment and clinical management of microbial infections. QS systems allow bacteria to adapt rapidly to harsh conditions, and are known to promote the formation of antibiotic tolerant biofilm communities. It is well known that biofilm is a recalcitrant mode of growth and it also increases bacterial resistance to conventional antibiotics. The pharmacological properties of coumarins have been well described, and these have included several that possess antimicrobial properties. More recently, reports have highlighted the potential role of coumarins as alternative therapeutic strategies based on their ability to block the QS signalling systems and to inhibit the formation of biofilms in clinically relevant pathogens. In addition to human infections, coumarins have also been found to be effective in controlling plant pathogens, infections in aquaculture, food spoilage and in reducing biofouling caused by eukaryotic organisms. Thus, the coumarin class of small molecule natural product are emerging as a promising strategy to combat bacterial infections in the new era of antimicrobial resistance.}, }
@article {pmid29383197, year = {2017}, author = {Phelan, JP and Reen, FJ and Caparros-Martin, JA and O'Connor, R and O'Gara, F}, title = {Rethinking the bile acid/gut microbiome axis in cancer.}, journal = {Oncotarget}, volume = {8}, number = {70}, pages = {115736-115747}, pmid = {29383197}, issn = {1949-2553}, abstract = {Dietary factors, probiotic agents, aging and antibiotics/medicines impact on gut microbiome composition leading to disturbances in localised microbial populations. The impact can be profound and underlies a plethora of human disorders, including the focus of this review; cancer. Compromised microbiome populations can alter bile acid signalling and produce distinct pathophysiological bile acid profiles. These in turn have been associated with cancer development and progression. Exposure to high levels of bile acids, combined with localised molecular/genome instability leads to the acquisition of bile mediated neoplastic alterations, generating apoptotic resistant proliferation phenotypes. However, in recent years, several studies have emerged advocating the therapeutic benefits of bile acid signalling in suppressing molecular and phenotypic hallmarks of cancer progression. These studies suggest that in some instances, bile acids may reduce cancer phenotypic effects, thereby limiting metastatic potential. In this review, we contextualise the current state of the art to propose that the bile acid/gut microbiome axis can influence cancer progression to the extent that classical in vitro cancer hallmarks of malignancy (cell invasion, cell migration, clonogenicity, and cell adhesion) are significantly reduced. We readily acknowledge the existence of a bile acid/gut microbiome axis in cancer initiation, however, in light of recent advances, we focus exclusively on the role of bile acids as potentially beneficial molecules in suppressing cancer progression. Finally, we theorise that suppressing aggressive malignant phenotypes through bile acid/gut microbiome axis modulation could uncover new and innovative disease management strategies for managing cancers in vulnerable cohorts.}, }
@article {pmid29382863, year = {2018}, author = {Di Francesco, L and Verrico, A and Asteriti, IA and Rovella, P and Cirigliano, P and Guarguaglini, G and Schininà, ME and Lavia, P}, title = {Visualization of human karyopherin beta-1/importin beta-1 interactions with protein partners in mitotic cells by co-immunoprecipitation and proximity ligation assays.}, journal = {Scientific reports}, volume = {8}, number = {1}, pages = {1850}, pmid = {29382863}, issn = {2045-2322}, mesh = {Biological Assay ; HeLa Cells ; Humans ; Image Processing, Computer-Assisted/*methods ; Immunoprecipitation/*methods ; *Mitosis ; Polymerase Chain Reaction ; Protein Interaction Domains and Motifs ; beta Karyopherins/*metabolism ; }, abstract = {Karyopherin beta-1/Importin beta-1 is a conserved nuclear transport receptor, acting in protein nuclear import in interphase and as a global regulator of mitosis. These pleiotropic functions reflect its ability to interact with, and regulate, different pathways during the cell cycle, operating as a major effector of the GTPase RAN. Importin beta-1 is overexpressed in cancers characterized by high genetic instability, an observation that highlights the importance of identifying its partners in mitosis. Here we present the first comprehensive profile of importin beta-1 interactors from human mitotic cells. By combining co-immunoprecipitation and proteome-wide mass spectrometry analysis of synchronized cell extracts, we identified expected (e.g., RAN and SUMO pathway factors) and novel mitotic interactors of importin beta-1, many with RNA-binding ability, that had not been previously associated with importin beta-1. These data complement interactomic studies of interphase transport pathways. We further developed automated proximity ligation assay (PLA) protocols to validate selected interactors. We succeeded in obtaining spatial and temporal resolution of genuine importin beta-1 interactions, which were visualized and localized in situ in intact mitotic cells. Further developments of PLA protocols will be helpful to dissect importin beta-1-orchestrated pathways during mitosis.}, }
@article {pmid29382070, year = {2018}, author = {D'Argenio, V}, title = {Human Microbiome Acquisition and Bioinformatic Challenges in Metagenomic Studies.}, journal = {International journal of molecular sciences}, volume = {19}, number = {2}, pages = {}, pmid = {29382070}, issn = {1422-0067}, mesh = {*Gastrointestinal Microbiome ; Genomics/*methods/standards ; Humans ; *Metagenome ; Transcriptome ; }, abstract = {The study of the human microbiome has become a very popular topic. Our microbial counterpart, in fact, appears to play an important role in human physiology and health maintenance. Accordingly, microbiome alterations have been reported in an increasing number of human diseases. Despite the huge amount of data produced to date, less is known on how a microbial dysbiosis effectively contributes to a specific pathology. To fill in this gap, other approaches for microbiome study, more comprehensive than 16S rRNA gene sequencing, i.e., shotgun metagenomics and metatranscriptomics, are becoming more widely used. Methods standardization and the development of specific pipelines for data analysis are required to contribute to and increase our understanding of the human microbiome relationship with health and disease status.}, }
@article {pmid29379536, year = {2018}, author = {Nobili, V and Putignani, L and Mosca, A and Del Chierico, F and Vernocchi, P and Alisi, A and Stronati, L and Cucchiara, S and Toscano, M and Drago, L}, title = {Bifidobacteria and lactobacilli in the gut microbiome of children with non-alcoholic fatty liver disease: which strains act as health players?.}, journal = {Archives of medical science : AMS}, volume = {14}, number = {1}, pages = {81-87}, pmid = {29379536}, issn = {1734-1922}, abstract = {INTRODUCTION: Non-alcoholic fatty liver disease (NAFLD), considered the leading cause of chronic liver disease in children, can often progress from non-alcoholic fatty liver (NAFL) to non-alcoholic steatohepatitis (NASH). It is clear that obesity is one of the main risk factors involved in NAFLD pathogenesis, even if specific mechanisms have yet to be elucidated. We investigated the distribution of intestinal bifidobacteria and lactobacilli in the stools of four groups of children: obese, obese with NAFL, obese with NASH, and healthy, age-matched controls (CTRLs).<br><br>MATERIAL AND METHODS: Sixty-one obese, NAFL and NASH children and 54 CTRLs were enrolled in the study. Anthropometric and metabolic parameters were measured for all subjects. All children with suspected NASH underwent liver biopsy. Bifidobacteria and lactobacilli were analysed in children's faecal samples, during a broader, 16S rRNA-based pyrosequencing analysis of the gut microbiome.<br><br>RESULTS: Three Bifidobacterium spp. (Bifidobacterium longum, Bifidobacterium bifidum, and Bifidobacterium adolescentis) and five Lactobacillus spp. (L. zeae, L. vaginalis, L. brevis, L. ruminis, and L. mucosae) frequently recurred in metagenomic analyses. Lactobacillus spp. increased in NAFL, NASH, or obese children compared to CTRLs. Particularly, L. mucosae was significantly higher in obese (p = 0.02426), NAFLD (p = 0.01313) and NASH (p = 0.01079) than in CTRLs. In contrast, Bifidobacterium spp. were more abundant in CTRLs, suggesting a protective and beneficial role of these microorganisms against the aforementioned diseases.<br><br>CONCLUSIONS: Bifidobacteria seem to have a protective role against the development of NAFLD and obesity, highlighting their possible use in developing novel, targeted and effective probiotics.}, }
@article {pmid29379216, year = {2018}, author = {Almeida, A and Shao, Y}, title = {Genome watch: Keeping tally in the microbiome.}, journal = {Nature reviews. Microbiology}, volume = {16}, number = {3}, pages = {124}, pmid = {29379216}, issn = {1740-1534}, mesh = {Animals ; Bacteria/classification/*genetics/isolation &amp; purification ; Biodiversity ; Gene Expression Profiling/*methods ; *Genome, Bacterial ; Humans ; *Metagenomics ; *Microbiota ; Nucleic Acid Amplification Techniques ; }, abstract = {This month's Genome Watch highlights how the development of new approaches for quantifying the human microbiome may pave the way for a better understanding of microbial shifts in the context of human health and disease.}, }
@article {pmid29378630, year = {2018}, author = {Kolde, R and Franzosa, EA and Rahnavard, G and Hall, AB and Vlamakis, H and Stevens, C and Daly, MJ and Xavier, RJ and Huttenhower, C}, title = {Host genetic variation and its microbiome interactions within the Human Microbiome Project.}, journal = {Genome medicine}, volume = {10}, number = {1}, pages = {6}, pmid = {29378630}, issn = {1756-994X}, support = {U54 DK102557/DK/NIDDK NIH HHS/United States ; U54 HG003067/HG/NHGRI NIH HHS/United States ; P30 DK043351/DK/NIDDK NIH HHS/United States ; 5U54HG003067-13/HG/NHGRI NIH HHS/United States ; U54 DE023798/DE/NIDCR NIH HHS/United States ; }, mesh = {*Genetic Variation ; Genotype ; Humans ; Metagenome ; Microbiota/*genetics ; Principal Component Analysis ; Sequence Analysis, DNA ; Tissue Donors ; }, abstract = {BACKGROUND: Despite the increasing recognition that microbial communities within the human body are linked to health, we have an incomplete understanding of the environmental and molecular interactions that shape the composition of these communities. Although host genetic factors play a role in these interactions, these factors have remained relatively unexplored given the requirement for large population-based cohorts in which both genotyping and microbiome characterization have been performed.<br><br>METHODS: We performed whole-genome sequencing of 298 donors from the Human Microbiome Project (HMP) healthy cohort study to accompany existing deep characterization of their microbiomes at various body sites. This analysis yielded an average sequencing depth of 32x, with which we identified 27 million (M) single nucleotide variants and 2.3&#xa0;M insertions-deletions.<br><br>RESULTS: Taxonomic composition and functional potential of the microbiome covaried significantly with genetic principal components in the gastrointestinal tract and oral communities, but not in the nares or vaginal microbiota. Example associations included validation of known associations between FUT2 secretor status, as well as a variant conferring hypolactasia near the LCT gene, with Bifidobacterium longum abundance in stool. The associations of microbial features with both high-level genetic attributes and single variants were specific to particular body sites, highlighting the opportunity to find unique genetic mechanisms controlling microbiome properties in the microbial communities from multiple body sites.<br><br>CONCLUSIONS: This study adds deep sequencing of host genomes to the body-wide microbiome sequences already extant from the HMP healthy cohort, creating a unique, versatile, and well-controlled reference for future studies seeking to identify host genetic modulators of the microbiome.}, }
@article {pmid29377607, year = {2018}, author = {Bolourian, A and Mojtahedi, Z}, title = {Immunosuppressants produced by Streptomyces: evolution, hygiene hypothesis, tumour rapalog resistance and probiotics.}, journal = {Environmental microbiology reports}, volume = {10}, number = {2}, pages = {123-126}, doi = {10.1111/1758-2229.12617}, pmid = {29377607}, issn = {1758-2229}, mesh = {Biological Evolution ; Drug Resistance ; Humans ; *Hygiene Hypothesis ; Immunosuppressive Agents/*metabolism/pharmacology ; Neoplasms/*drug therapy ; Sirolimus/chemistry/metabolism/pharmacology ; Streptomyces/*metabolism ; Tacrolimus/chemistry/metabolism/pharmacology ; }, abstract = {Resistance to a drug and the suppression of inflammatory disorders with immunosuppressive drugs might have happened upon exposure to natural compounds during evolution. Streptomycetes are soil bacteria, but they produce therapeutic drugs. They have been reported to be the low-abundant members of mucosal microbiomes with a higher prevalence in nonhumans ingesting soil compared with humans. Their lower abundance in the human microbiome might be the representations of our current hygienic lifestyle. We suggest that the Streptomyces bacteria producing antiproliferative/immunosuppressive compounds (e.g., rapamycin and tacrolimus) contribute to the rapalog resistance of certain mucosal tumours (e.g., colon cancer) and the 'hygiene hypothesis'. If so, the shortage of exposure to these compounds in the current lifestyle might be an underlying reason for the increase of inflammatory diseases, such as inflammatory bowel diseases (IBD). An investigation on adding certain Streptomycetes (e.g., S. hygroscopicus and S. tubercidicus) to the list of probiotics against inflammatory diseases would be an interesting research area in the future.}, }
@article {pmid29373999, year = {2018}, author = {Fuks, G and Elgart, M and Amir, A and Zeisel, A and Turnbaugh, PJ and Soen, Y and Shental, N}, title = {Combining 16S rRNA gene variable regions enables high-resolution microbial community profiling.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {17}, pmid = {29373999}, issn = {2049-2618}, support = {R01 HL122593/HL/NHLBI NIH HHS/United States ; 3-11174//Ministry of Science and Technology, Israel/International ; }, mesh = {Algorithms ; Animals ; Bacteria/classification ; Computer Simulation ; DNA Probes/genetics ; DNA, Bacterial/genetics ; Drosophila melanogaster/*microbiology ; Microbiota ; Phylogeny ; Polymerase Chain Reaction/*methods ; RNA, Ribosomal, 16S/*genetics ; Sequence Analysis, DNA/*methods ; }, abstract = {BACKGROUND: Most of our knowledge about the remarkable microbial diversity on Earth comes from sequencing the 16S rRNA gene. The use of next-generation sequencing methods has increased sample number and sequencing depth, but the read length of the most widely used sequencing platforms today is quite short, requiring the researcher to choose a subset of the gene to sequence (typically 16-33% of the total length). Thus, many bacteria may share the same amplified region, and the resolution of profiling is inherently limited. Platforms that offer ultra-long read lengths, whole genome shotgun sequencing approaches, and computational frameworks formerly suggested by us and by others all allow different ways to circumvent this problem yet suffer various shortcomings. There is a need for a simple and low-cost 16S rRNA gene-based profiling approach that harnesses the short read length to provide a much larger coverage of the gene to allow for high resolution, even in harsh conditions of low bacterial biomass and fragmented DNA.<br><br>RESULTS: This manuscript suggests Short MUltiple Regions Framework (SMURF), a method to combine sequencing results from different PCR-amplified regions to provide one coherent profiling. The de facto amplicon length is the total length of all amplified regions, thus providing much higher resolution compared to current techniques. Computationally, the method solves a convex optimization problem that allows extremely fast reconstruction and requires only moderate memory. We demonstrate the increase in resolution by in silico simulations and by profiling two mock mixtures and real-world biological samples. Reanalyzing a mock mixture from the Human Microbiome Project achieved about twofold improvement in resolution when combing two independent regions. Using a custom set of six primer pairs spanning about 1200&#xa0;bp (80%) of the 16S rRNA gene, we were able to achieve ~&#x2009;100-fold improvement in resolution compared to a single region, over a mock mixture of common human gut bacterial isolates. Finally, the profiling of a Drosophila melanogaster microbiome using the set of six primer pairs provided a ~&#x2009;100-fold increase in resolution and thus enabling efficient downstream analysis.<br><br>CONCLUSIONS: SMURF enables the identification of near full-length 16S rRNA gene sequences in microbial communities, having resolution superior compared to current techniques. It may be applied to standard sample preparation protocols with very little modifications. SMURF also paves the way to high-resolution profiling of low-biomass and fragmented DNA, e.g., in the case of formalin-fixed and paraffin-embedded samples, fossil-derived DNA, or DNA exposed to other degrading conditions. The approach is not restricted to combining amplicons of the 16S rRNA gene and may be applied to any set of amplicons, e.g., in multilocus sequence typing (MLST).}, }
@article {pmid29373532, year = {2018}, author = {Harper, A and Naghibi, MM and Garcha, D}, title = {The Role of Bacteria, Probiotics and Diet in Irritable Bowel Syndrome.}, journal = {Foods (Basel, Switzerland)}, volume = {7}, number = {2}, pages = {}, pmid = {29373532}, issn = {2304-8158}, abstract = {Irritable bowel syndrome is a highly prevalent gastrointestinal disorder that threatens the quality of life of millions and poses a substantial financial burden on healthcare systems around the world. Intense research into the human microbiome has led to fascinating discoveries which directly and indirectly implicate the diversity and function of this occult organ in irritable bowel syndrome (IBS) pathophysiology. The benefit of manipulating the gastrointestinal microbiota with diet and probiotics to improve symptoms has been demonstrated in a wealth of both animal and human studies. The positive and negative mechanistic roles bacteria play in IBS will be explored and practical probiotic and dietary choices offered.}, }
@article {pmid29359197, year = {2018}, author = {Shaffer, M and Lozupone, C}, title = {Prevalence and Source of Fecal and Oral Bacteria on Infant, Child, and Adult Hands.}, journal = {mSystems}, volume = {3}, number = {1}, pages = {}, pmid = {29359197}, issn = {2379-5077}, support = {T15 LM007079/LM/NLM NIH HHS/United States ; }, abstract = {Modern hygienic practices are applied to avoid exposure to pathogens that spread via fecal-oral transmission. Despite this, the gastrointestinal tract is quickly colonized by fecal microbes. The hands are an important vector for the transmission of microbes, but the frequency at which fecal and oral microbes exist on hands and the source of those microbes have not been extensively described. Using data from a previous study that characterized the fecal, oral, and skin microbiota from 73 families, we found a significant incidence of fecal and oral microbes on hands. Of palms, 48.9% had fecal signal and 67.2% had oral signal. Fecal, oral, and forehead microbes were tracked to family members and an individual's own palms far more often than to unrelated individuals and showed relationships with age, gender, and parental status. For instance, oral microbes that were specifically sourced to the same individual (oneself) were most common on infant palms; mothers had more infant-child-sourced and oral-sourced microbes on their palms than nonparents. Fecal microbes on palms more often sourced to members of the family than unrelated individuals, but more often to other members of the family than oneself. This study supports that the hands are an important vector for the transfer of fecal and oral microbes within families. IMPORTANCE Bacteria live all around us, and we are constantly exposed to them during our everyday lives. Modern standards of hygiene aim to limit exposure to fecal bacteria, and yet bacteria rapidly colonize the gut in early life and following antibacterial treatment. Exposures to fecal and oral microbes provide risk of disease, but are also necessary since commensal microbes play important roles in health. This work establishes that bacteria of both fecal and oral origins are commonly found on hands. It also establishes that the uniqueness of fecal and oral bacterial communities across people can allow for determination of the likely individual from whom the fecal and oral bacteria came. These techniques allow for understanding the hands as a vector for microbial transmission within families and across populations, which has important implications for public health.}, }
@article {pmid29359193, year = {2018}, author = {Liu, Z and Cichocki, N and Bonk, F and Günther, S and Schattenberg, F and Harms, H and Centler, F and Müller, S}, title = {Ecological Stability Properties of Microbial Communities Assessed by Flow Cytometry.}, journal = {mSphere}, volume = {3}, number = {1}, pages = {}, pmid = {29359193}, issn = {2379-5042}, abstract = {Natural microbial communities affect human life in countless ways, ranging from global biogeochemical cycles to the treatment of wastewater and health via the human microbiome. In order to probe, monitor, and eventually control these communities, fast detection and evaluation methods are required. In order to facilitate rapid community analysis and monitor a community's dynamic behavior with high resolution, we here apply community flow cytometry, which provides single-cell-based high-dimensional data characterizing communities with high acuity over time. To interpret time series data, we draw inspiration from macroecology, in which a rich set of concepts has been developed for describing population dynamics. We focus on the stability paradigm as a promising candidate to interpret such data in an intuitive and actionable way and present a rapid workflow to monitor stability properties of complex microbial ecosystems. Based on single-cell data, we compute the stability properties resistance, resilience, displacement speed, and elasticity. For resilience, we also introduce a method which can be implemented for continuous online community monitoring. The proposed workflow was tested in a long-term continuous reactor experiment employing both an artificial and a complex microbial community, which were exposed to identical short-term disturbances. The computed stability properties uncovered the superior stability of the complex community and demonstrated the global applicability of the protocol to any microbiome. The workflow is able to support high temporal sample densities below bacterial generation times. This may provide new opportunities to unravel unknown ecological paradigms of natural microbial communities, with applications to environmental, biotechnological, and health-related microbiomes. IMPORTANCE Microbial communities drive many processes which affect human well-being directly, as in the human microbiome, or indirectly, as in natural environments or in biotechnological applications. Due to their complexity, their dynamics over time is difficult to monitor, and current sequence-based approaches are limited with respect to the temporal resolution. However, in order to eventually control microbial community dynamics, monitoring schemes of high temporal resolution are required. Flow cytometry provides single-cell-based data in the required temporal resolution, and we here use such data to compute stability properties as easy to interpret univariate indicators of microbial community dynamics. Such monitoring tools will allow for a fast, continuous, and cost-effective screening of stability states of microbiomes. Applicable to various environments, including bioreactors, surface water, and the human body, it will contribute to the development of control schemes to manipulate microbial community structures and performances.}, }
@article {pmid29348922, year = {2018}, author = {Alou, MT and Ndongo, S and Frégère, L and Labas, N and Andrieu, C and Richez, M and Couderc, C and Baudoin, JP and Abrahão, J and Brah, S and Diallo, A and Sokhna, C and Cassir, N and La Scola, B and Cadoret, F and Raoult, D}, title = {Taxonogenomic description of four new Clostridium species isolated from human gut: 'Clostridium amazonitimonense', 'Clostridium merdae', 'Clostridium massilidielmoense' and 'Clostridium nigeriense'.}, journal = {New microbes and new infections}, volume = {21}, number = {}, pages = {128-139}, pmid = {29348922}, issn = {2052-2975}, abstract = {Culturomics investigates microbial diversity of the human microbiome by combining diversified culture conditions, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and 16S rRNA gene identification. The present study allowed identification of four putative new Clostridium sensu stricto species: 'Clostridium amazonitimonense' strain LF2[T], 'Clostridium massilidielmoense' strain MT26[T], 'Clostridium nigeriense' strain Marseille-P2414[T] and 'Clostridium merdae' strain Marseille-P2953[T], which we describe using the concept of taxonogenomics. We describe the main characteristics of each bacterium and present their complete genome sequence and annotation.}, }
@article {pmid29346509, year = {2018}, author = {Zhang, J and Wei, Z and Chen, J}, title = {A distance-based approach for testing the mediation effect of the human microbiome.}, journal = {Bioinformatics (Oxford, England)}, volume = {34}, number = {11}, pages = {1875-1883}, doi = {10.1093/bioinformatics/bty014}, pmid = {29346509}, issn = {1367-4811}, mesh = {Bacteria/genetics ; Computational Biology/*methods ; Computer Simulation ; Gastrointestinal Microbiome/genetics ; Microbiota/*genetics ; *Phylogeny ; *Software ; }, abstract = {MOTIVATION: Recent studies have revealed a complex interplay between environment, the human microbiome and health and disease. Mediation analysis of the human microbiome in these complex relationships could potentially provide insights into the role of the microbiome in the etiology of disease and, more importantly, lead to novel clinical interventions by modulating the microbiome. However, due to the high dimensionality, sparsity, non-normality and phylogenetic structure of microbiome data, none of the existing methods are suitable for testing such clinically important mediation effect.<br><br>RESULTS: We propose a distance-based approach for testing the mediation effect of the human microbiome. In the framework, the nonlinear relationship between the human microbiome and independent/dependent variables is captured implicitly through the use of sample-wise ecological distances, and the phylogenetic tree information is conveniently incorporated by using phylogeny-based distance metrics. Multiple distance metrics are utilized to maximize the power to detect various types of mediation effect. Simulation studies demonstrate that our method has correct Type I error control, and is robust and powerful under various mediation models. Application to a real gut microbiome dataset revealed that the association between the dietary fiber intake and body mass index was mediated by the gut microbiome.<br><br>An R package 'MedTest' is freely available at https://github.com/jchen1981/MedTest.<br><br>CONTACT: zhiwei@njit.edu or chen.jun2@mayo.edu.<br><br>SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.}, }
@article {pmid29341791, year = {2018}, author = {Korownyk, C and Liu, F and Garrison, S}, title = {Population level evidence for seasonality of the human microbiome.}, journal = {Chronobiology international}, volume = {35}, number = {4}, pages = {573-577}, doi = {10.1080/07420528.2018.1424718}, pmid = {29341791}, issn = {1525-6073}, mesh = {Flatulence/*microbiology ; Halitosis/*microbiology ; Humans ; Internet ; *Microbiota ; *Odorants ; Population Health ; Search Engine ; *Seasons ; Time Factors ; }, abstract = {The objective of this study is to determine whether human body odors undergo seasonal modulation. We utilized google trends search volume from the United States of America from January 1, 2010 to June 24, 2017 for a number of predetermined body odors. Regression modeling of time series data was completed. Our primary outcome was to determine the proportion of the variability in Internet searches for each unpleasant odor (about the mean) that is explained by a seasonal model. We determined that the seasonal (sinusoidal) model provided a significantly better fit than the null model (best straight line fit) for all searches relating to human body odors (P <.0001 for each). This effect was easily visible to the naked eye in the raw time series data. Seasonality explained 88% of the variability in search volume for flatulence (i.e. R2 = 0.88), 65% of the variability in search volume for axillary odor, 60% of the variability in search volume for foot odor, and 58% of the variability in search volume for bad breath. Flatulence and bad breath tended to peak in January, foot odor in February, and Axillary odor in July. We conclude that searching by the general public for information on unpleasant body odors undergoes substantial seasonal variation, with the timing of peaks and troughs varying with the body part involved. The symptom burden of such smells may have a similar seasonal variation, as might the composition of the commensal bacterial microflora that play a role in creating them.}, }
@article {pmid29340239, year = {2018}, author = {Tithi, SS and Aylward, FO and Jensen, RV and Zhang, L}, title = {FastViromeExplorer: a pipeline for virus and phage identification and abundance profiling in metagenomics data.}, journal = {PeerJ}, volume = {6}, number = {}, pages = {e4227}, pmid = {29340239}, issn = {2167-8359}, abstract = {With the increase in the availability of metagenomic data generated by next generation sequencing, there is an urgent need for fast and accurate tools for identifying viruses in host-associated and environmental samples. In this paper, we developed a stand-alone pipeline called FastViromeExplorer for the detection and abundance quantification of viruses and phages in large metagenomic datasets by performing rapid searches of virus and phage sequence databases. Both simulated and real data from human microbiome and ocean environmental samples are used to validate FastViromeExplorer as a reliable tool to quickly and accurately identify viruses and their abundances in large datasets.}, }
@article {pmid29340028, year = {2017}, author = {Guerrero-Preston, R and White, JR and Godoy-Vitorino, F and Rodríguez-Hilario, A and Navarro, K and González, H and Michailidi, C and Jedlicka, A and Canapp, S and Bondy, J and Dziedzic, A and Mora-Lagos, B and Rivera-Alvarez, G and Ili-Gangas, C and Brebi-Mieville, P and Westra, W and Koch, W and Kang, H and Marchionni, L and Kim, Y and Sidransky, D}, title = {High-resolution microbiome profiling uncovers Fusobacterium nucleatum, Lactobacillus gasseri/johnsonii, and Lactobacillus vaginalis associated to oral and oropharyngeal cancer in saliva from HPV positive and HPV negative patients treated with surgery and chemo-radiation.}, journal = {Oncotarget}, volume = {8}, number = {67}, pages = {110931-110948}, pmid = {29340028}, issn = {1949-2553}, support = {RC2 DE020957/DE/NIDCR NIH HHS/United States ; P50 DE019032/DE/NIDCR NIH HHS/United States ; R01 CA121113/CA/NCI NIH HHS/United States ; K01 CA164092/CA/NCI NIH HHS/United States ; U01 CA084986/CA/NCI NIH HHS/United States ; P20 GM103475/GM/NIGMS NIH HHS/United States ; }, abstract = {Microbiome studies show altered microbiota in head and neck squamous cell carcinoma (HNSCC), both in terms of taxonomic composition and metabolic capacity. These studies utilized a traditional bioinformatics methodology, which allows for accurate taxonomic assignment down to the genus level, but cannot accurately resolve species level membership. We applied Resphera Insight, a high-resolution methodology for 16S rRNA taxonomic assignment that is able to provide species-level context in its assignments of 16S rRNA next generation sequencing (NGS) data. Resphera Insight applied to saliva samples from HNSCC patients and healthy controls led to the discovery that a subset of HNSCC saliva samples is significantly enriched with commensal species from the vaginal flora, including Lactobacillus gasseri/johnsonii (710x higher in saliva) and Lactobacillus vaginalis (52x higher in saliva). These species were not observed in normal saliva from Johns Hopkins patients, nor in 16S rRNA NGS saliva samples from the Human Microbiome Project (HMP). Interestingly, both species were only observed in saliva from Human Papilloma Virus (HPV) positive and HPV negative oropharyngeal cancer patients. We confirmed the representation of both species in HMP data obtained from mid-vagina (n=128) and vaginal introitus (n=121) samples. Resphera Insight also led to the discovery that Fusobacterium nucleatum, an oral cavity flora commensal bacterium linked to colon cancer, is enriched (600x higher) in saliva from a subset of HNSCC patients with advanced tumors stages. Together, these high-resolution analyses on 583 samples suggest a possible role for bacterial species in the therapeutic outcome of HPV positive and HPV negative HNSCC patients.}, }
@article {pmid29332963, year = {2017}, author = {Roszyk, E and Puszczewicz, M}, title = {Role of human microbiome and selected bacterial infections in the pathogenesis of rheumatoid arthritis.}, journal = {Reumatologia}, volume = {55}, number = {5}, pages = {242-250}, pmid = {29332963}, issn = {0034-6233}, abstract = {Microorganisms inhabiting human body form a complex ecosystem. The mutual influence of the microbiome and the immune system of the host constitute the basis for numerous diseases, e.g. pseudomembranous colitis, inflammatory bowel disease, type 1 diabetes, atopic diseases, obesity, reactive arthritis. New molecular diagnostic methods and multi-center studies may help in understanding of the role of microbiota in health and disease. Rheumatoid arthritis has a multi-faceted etiology, and its causes are not entirely understood. There are indications for the influence of microbiomes of oral cavity, intestines, lungs and urinary tract on the development of rheumatoid arthritis. Interactions between microorganisms and human immune system play role in the pathogenesis of the disease.}, }
@article {pmid29330190, year = {2018}, author = {Kraemer, JG and Ramette, A and Aebi, S and Oppliger, A and Hilty, M}, title = {Influence of Pig Farming on the Human Nasal Microbiota: Key Role of Airborne Microbial Communities.}, journal = {Applied and environmental microbiology}, volume = {84}, number = {6}, pages = {}, pmid = {29330190}, issn = {1098-5336}, mesh = {*Agriculture ; *Air Microbiology ; Animals ; Bacteria/classification/genetics/isolation &amp; purification ; Biodiversity ; Cattle ; Cross-Sectional Studies ; Dust ; Farmers ; Farms ; Fungi/classification/genetics/isolation &amp; purification ; Humans ; Male ; *Microbiota/genetics ; Nose/*microbiology ; RNA, Ribosomal, 16S/genetics ; Swine ; }, abstract = {It has been hypothesized that the environment can influence the composition of the nasal microbiota. However, the direct influence of pig farming on the anterior and posterior nasal microbiota is unknown. Using a cross-sectional design, pig farms (n = 28) were visited in 2014 to 2015, and nasal swabs from 43 pig farmers and 56 pigs, as well as 27 air samples taken in the vicinity of the pig enclosures, were collected. As controls, nasal swabs from 17 cow farmers and 26 non-animal-exposed individuals were also included. Analyses of the microbiota were performed based on 16S rRNA amplicon sequencing and the DADA2 pipeline to define sequence variants (SVs). We found that pig farming is strongly associated with specific microbial signatures (including alpha- and beta-diversity), which are reflected in the microbiota of the human nose. Furthermore, the microbial communities were more similar within the same farm compared to between the different farms, indicating a specific microbiota pattern for each pig farm. In total, there were 82 SVs that occurred significantly more abundantly in samples from pig farms than from cow farmers and nonexposed individuals (i.e., the core pig farm microbiota). Of these, nine SVs were significantly associated with the posterior part of the human nose. The results strongly indicate that pig farming is associated with a distinct human nose microbiota. Finally, the community structures derived by the DADA2 pipeline showed an excellent agreement with the outputs of the mothur pipeline which was revealed by procrustes analyses. IMPORTANCE The knowledge about the influence of animal keeping on the human microbiome is important. Previous research has shown that pets significantly affect the microbial communities of humans. However, the effect of animal farming on the human microbiota is less clear, although it is known that the air at farms and, in particular, at pig farms is charged with large amounts of dust, bacteria, and fungi. In this study, we simultaneously investigated the nasal microbiota of pigs, humans, and the environment at pig farms. We reveal an enormous impact of pig farming on the human nasal microbiota which is far more pronounced compared to cow farming. In addition, we analyzed the airborne microbiota and found significant associations suggesting an animal-human transmission of the microbiota within pig farms. We also reveal that microbial patterns are farm specific, suggesting that the environment influences animals and humans in a similar manner.}, }
@article {pmid29325418, year = {2018}, author = {Balskus, EP}, title = {The Human Microbiome.}, journal = {ACS infectious diseases}, volume = {4}, number = {1}, pages = {1-2}, doi = {10.1021/acsinfecdis.7b00248}, pmid = {29325418}, issn = {2373-8227}, mesh = {Drug Discovery ; Host-Pathogen Interactions ; Humans ; *Microbiota ; }, }
@article {pmid29321635, year = {2018}, author = {Brüggemann, H and Jensen, A and Nazipi, S and Aslan, H and Meyer, RL and Poehlein, A and Brzuszkiewicz, E and Al-Zeer, MA and Brinkmann, V and Söderquist, B}, title = {Pan-genome analysis of the genus Finegoldia identifies two distinct clades, strain-specific heterogeneity, and putative virulence factors.}, journal = {Scientific reports}, volume = {8}, number = {1}, pages = {266}, pmid = {29321635}, issn = {2045-2322}, mesh = {Base Composition ; Gene Order ; *Genetic Heterogeneity ; Genetic Loci ; Genome Size ; *Genome, Bacterial ; Genomics/methods ; *Genotype ; Gram-Positive Bacterial Infections/microbiology ; Gram-Positive Cocci/*classification/*genetics/pathogenicity/ultrastructure ; Host-Pathogen Interactions ; Phylogeny ; Virulence Factors/genetics ; }, abstract = {Finegoldia magna, a Gram-positive anaerobic coccus, is an opportunistic pathogen, associated with medical device-related infections. F. magna is the only described species of the genus Finegoldia. We report the analysis of 17 genomes of Finegoldia isolates. Phylogenomic analyses showed that the Finegoldia population can be divided into two distinct clades, with an average nucleotide identity of 90.7%. One clade contains strains of F. magna, whereas the other clade includes more heterogeneous strains, hereafter tentatively named "Finegoldia nericia". The latter species appears to be more abundant in the human microbiome. Surface structure differences between strains of F. magna and "F. nericia" were detected by microscopy. Strain-specific heterogeneity is high and previously identified host-interacting factors are present only in subsets of "F. nericia" and F. magna strains. However, all genomes encode multiple host factor-binding proteins such as albumin-, collagen-, and immunoglobulin-binding proteins, and two to four copies of CAMP (Christie-Atkins-Munch-Petersen) factors; in accordance, most strains show a positive CAMP reaction for co-hemolysis. Our work sheds new light of the genus Finegoldia and its ability to bind host components. Future research should explore if the genomic differences identified here affect the potential of different Finegoldia species and strains to cause opportunistic infections.}, }
@article {pmid29321519, year = {2018}, author = {Stokholm, J and Blaser, MJ and Thorsen, J and Rasmussen, MA and Waage, J and Vinding, RK and Schoos, AM and Kunøe, A and Fink, NR and Chawes, BL and Bønnelykke, K and Brejnrod, AD and Mortensen, MS and Al-Soud, WA and Sørensen, SJ and Bisgaard, H}, title = {Maturation of the gut microbiome and risk of asthma in childhood.}, journal = {Nature communications}, volume = {9}, number = {1}, pages = {141}, pmid = {29321519}, issn = {2041-1723}, support = {R01 DK090989/DK/NIDDK NIH HHS/United States ; }, mesh = {Asthma/*epidemiology/genetics/microbiology ; Bacteroides/genetics ; Bifidobacterium/genetics ; *Child Development ; Child, Preschool ; Enterobacteriaceae/genetics ; Enterococcus/genetics ; Female ; Gastrointestinal Microbiome/*genetics ; Humans ; Infant ; Male ; Mothers ; RNA, Ribosomal, 16S/*genetics ; Risk ; Staphylococcus/genetics ; Streptococcus/genetics ; Veillonella/genetics ; }, abstract = {The composition of the human gut microbiome matures within the first years of life. It has been hypothesized that microbial compositions in this period can cause immune dysregulations and potentially cause asthma. Here we show, by associating gut microbial composition from 16S rRNA gene amplicon sequencing during the first year of life with subsequent risk of asthma in 690 participants, that 1-year-old children with an immature microbial composition have an increased risk of asthma at age 5 years. This association is only apparent among children born to asthmatic mothers, suggesting that lacking microbial stimulation during the first year of life can trigger their inherited asthma risk. Conversely, adequate maturation of the gut microbiome in this period may protect these pre-disposed children.}, }
@article {pmid29311644, year = {2018}, author = {Schirmer, M and Franzosa, EA and Lloyd-Price, J and McIver, LJ and Schwager, R and Poon, TW and Ananthakrishnan, AN and Andrews, E and Barron, G and Lake, K and Prasad, M and Sauk, J and Stevens, B and Wilson, RG and Braun, J and Denson, LA and Kugathasan, S and McGovern, DPB and Vlamakis, H and Xavier, RJ and Huttenhower, C}, title = {Dynamics of metatranscription in the inflammatory bowel disease gut microbiome.}, journal = {Nature microbiology}, volume = {3}, number = {3}, pages = {337-346}, pmid = {29311644}, issn = {2058-5276}, support = {U54 DK102557/DK/NIDDK NIH HHS/United States ; U01 DK062413/DK/NIDDK NIH HHS/United States ; P30 DK043351/DK/NIDDK NIH HHS/United States ; P01 DK046763/DK/NIDDK NIH HHS/United States ; UL1 TR001881/TR/NCATS NIH HHS/United States ; P30 DK078392/DK/NIDDK NIH HHS/United States ; R01 DK092405/DK/NIDDK NIH HHS/United States ; }, mesh = {Adolescent ; Adult ; Child ; Colitis, Ulcerative/microbiology ; Crohn Disease/microbiology ; Dysbiosis ; Feces/microbiology ; Female ; Gastrointestinal Microbiome/*genetics ; Gene Expression Profiling ; Humans ; Inflammatory Bowel Diseases/*microbiology ; Longitudinal Studies ; Male ; *Metagenomics ; Phenotype ; *Transcription, Genetic ; Young Adult ; }, abstract = {Inflammatory bowel disease (IBD) is a group of chronic diseases of the digestive tract that affects millions of people worldwide. Genetic, environmental and microbial factors have been implicated in the onset and exacerbation of IBD. However, the mechanisms associating gut microbial dysbioses and aberrant immune responses remain largely unknown. The integrative Human Microbiome Project seeks to close these gaps by examining the dynamics of microbiome functionality in disease by profiling the gut microbiomes of >100 individuals sampled over a 1-year period. Here, we present the first results based on 78 paired faecal metagenomes and metatranscriptomes, and 222 additional metagenomes from 59 patients with Crohn's disease, 34 with ulcerative colitis and 24 non-IBD control patients. We demonstrate several cases in which measures of microbial gene expression in the inflamed gut can be informative relative to metagenomic profiles of functional potential. First, although many microbial organisms exhibited concordant DNA and RNA abundances, we also detected species-specific biases in transcriptional activity, revealing predominant transcription of pathways by individual microorganisms per host (for example, by Faecalibacterium prausnitzii). Thus, a loss of these organisms in disease may have more far-reaching consequences than suggested by their genomic abundances. Furthermore, we identified organisms that were metagenomically abundant but inactive or dormant in the gut with little or no expression (for example, Dialister invisus). Last, certain disease-specific microbial characteristics were more pronounced or only detectable at the transcript level, such as pathways that were predominantly expressed by different organisms in patients with IBD (for example, Bacteroides vulgatus and Alistipes putredinis). This provides potential insights into gut microbial pathway transcription that can vary over time, inducing phenotypical changes that are complementary to those linked to metagenomic abundances. The study's results highlight the strength of analysing both the activity and the presence of gut microorganisms to provide insight into the role of the microbiome in IBD.}, }
@article {pmid29311119, year = {2018}, author = {Clemente, JC and Manasson, J and Scher, JU}, title = {The role of the gut microbiome in systemic inflammatory disease.}, journal = {BMJ (Clinical research ed.)}, volume = {360}, number = {}, pages = {j5145}, pmid = {29311119}, issn = {1756-1833}, support = {K23 AR064318/AR/NIAMS NIH HHS/United States ; R03 AR072182/AR/NIAMS NIH HHS/United States ; S10 OD018522/OD/NIH HHS/United States ; T32 AR069515/AR/NIAMS NIH HHS/United States ; }, mesh = {Autoimmune Diseases/immunology/*microbiology ; Fecal Microbiota Transplantation/methods ; Feeding Behavior/*physiology ; Gastrointestinal Microbiome/*immunology/physiology ; Humans ; Inflammation/immunology/*microbiology ; Inflammatory Bowel Diseases/immunology/*microbiology/pathology ; Microbiota ; Mucous Membrane/immunology/*microbiology ; Prebiotics ; Probiotics ; }, abstract = {The role of the gut microbiome in models of inflammatory and autoimmune disease is now well characterized. Renewed interest in the human microbiome and its metabolites, as well as notable advances in host mucosal immunology, has opened multiple avenues of research to potentially modulate inflammatory responses. The complexity and interdependence of these diet-microbe-metabolite-host interactions are rapidly being unraveled. Importantly, most of the progress in the field comes from new knowledge about the functional properties of these microorganisms in physiology and their effect in mucosal immunity and distal inflammation. This review summarizes the preclinical and clinical evidence on how dietary, probiotic, prebiotic, and microbiome based therapeutics affect our understanding of wellness and disease, particularly in autoimmunity.}, }
@article {pmid29282061, year = {2017}, author = {Davenport, ER and Sanders, JG and Song, SJ and Amato, KR and Clark, AG and Knight, R}, title = {The human microbiome in evolution.}, journal = {BMC biology}, volume = {15}, number = {1}, pages = {127}, pmid = {29282061}, issn = {1741-7007}, support = {F32 DK109595/DK/NIDDK NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Animals ; *Biological Evolution ; Gastrointestinal Microbiome/physiology ; Host Specificity ; Humans ; Microbiota/*physiology ; Phylogeny ; }, abstract = {The trillions of microbes living in the gut-the gut microbiota-play an important role in human biology and disease. While much has been done to explore its diversity, a full understanding of our microbiomes demands an evolutionary perspective. In this review, we compare microbiomes from human populations, placing them in the context of microbes from humanity's near and distant animal relatives. We discuss potential mechanisms to generate host-specific microbiome configurations and the consequences of disrupting those configurations. Finally, we propose that this broader phylogenetic perspective is useful for understanding the mechanisms underlying human-microbiome interactions.}, }
@article {pmid29281638, year = {2017}, author = {Lo, C and Marculescu, R}, title = {MPLasso: Inferring microbial association networks using prior microbial knowledge.}, journal = {PLoS computational biology}, volume = {13}, number = {12}, pages = {e1005915}, pmid = {29281638}, issn = {1553-7358}, mesh = {Algorithms ; Computational Biology ; Data Mining ; Databases, Genetic ; Humans ; Machine Learning ; Microbial Consortia/genetics/*physiology ; Microbial Interactions/*physiology ; Microbiota/genetics/*physiology ; Models, Biological ; }, abstract = {Due to the recent advances in high-throughput sequencing technologies, it becomes possible to directly analyze microbial communities in human body and environment. To understand how microbial communities adapt, develop, and interact with the human body and the surrounding environment, one of the fundamental challenges is to infer the interactions among different microbes. However, due to the compositional and high-dimensional nature of microbial data, statistical inference cannot offer reliable results. Consequently, new approaches that can accurately and robustly estimate the associations (putative interactions) among microbes are needed to analyze such compositional and high-dimensional data. We propose a novel framework called Microbial Prior Lasso (MPLasso) which integrates graph learning algorithm with microbial co-occurrences and associations obtained from scientific literature by using automated text mining. We show that MPLasso outperforms existing models in terms of accuracy, microbial network recovery rate, and reproducibility. Furthermore, the association networks we obtain from the Human Microbiome Project datasets show credible results when compared against laboratory data.}, }
@article {pmid29277868, year = {2018}, author = {Maltez Thomas, A and Prata Lima, F and Maria Silva Moura, L and Maria da Silva, A and Dias-Neto, E and Setubal, JC}, title = {Comparative Metagenomics.}, journal = {Methods in molecular biology (Clifton, N.J.)}, volume = {1704}, number = {}, pages = {243-260}, doi = {10.1007/978-1-4939-7463-4_8}, pmid = {29277868}, issn = {1940-6029}, mesh = {Computational Biology ; Humans ; Metagenomics/*methods ; *Microbiota ; Mouth Mucosa/*microbiology ; Sequence Analysis, DNA/methods ; Software ; Tongue/*microbiology ; }, abstract = {Thanks in large part to newer, better, and cheaper DNA sequencing technologies, an enormous number of metagenomic sequence datasets have been and continue to be generated, covering a huge variety of environmental niches, including several different human body sites. Comparing these metagenomes and identifying their commonalities and differences is a challenging task, due not only to the large amounts of data, but also because there are several methodological considerations that need to be taken into account to ensure an appropriate and sound comparison between datasets. In this chapter, we describe current techniques aimed at comparing metagenomes generated by 16S ribosomal RNA and shotgun DNA sequencing, emphasizing methodological issues that arise in these comparative studies. We provide a detailed case study to illustrate some of these techniques using data from the Human Microbiome Project comparing the microbial communities from ten buccal mucosa samples with ten tongue dorsum samples in terms of alpha diversity, beta diversity, and their taxonomic and functional profiles.}, }
@article {pmid29276775, year = {2018}, author = {Van Dyke, TE and Diaz, PI and Moutsopoulos, N and Alekseyenko, AV and Ioannidou, E}, title = {Task Force on Design and Analysis in Oral Health Research: Host-Microbiome Interactions in Dysbiosis.}, journal = {JDR clinical and translational research}, volume = {3}, number = {1}, pages = {6-9}, pmid = {29276775}, issn = {2380-0844}, support = {R21 AR067459/AR/NIAMS NIH HHS/United States ; R01 DE025383/DE/NIDCR NIH HHS/United States ; R01 DE025020/DE/NIDCR NIH HHS/United States ; R34 DE027410/DE/NIDCR NIH HHS/United States ; R21 DE023967/DE/NIDCR NIH HHS/United States ; R01 DE021578/DE/NIDCR NIH HHS/United States ; }, abstract = {Knowledge Transfer Statement: This article discusses the proceedings of the conference organized by the Task Force on Design and Analysis in Oral Health Research on the new advances in host-microbiome interactions, analytical methods, and their implication in inflammatory periodontal disease management.}, }
@article {pmid29269494, year = {2018}, author = {Collins, SL and McMillan, A and Seney, S and van der Veer, C and Kort, R and Sumarah, MW and Reid, G}, title = {Promising Prebiotic Candidate Established by Evaluation of Lactitol, Lactulose, Raffinose, and Oligofructose for Maintenance of a Lactobacillus-Dominated Vaginal Microbiota.}, journal = {Applied and environmental microbiology}, volume = {84}, number = {5}, pages = {}, pmid = {29269494}, issn = {1098-5336}, support = {//CIHR/Canada ; }, mesh = {Dysbiosis/drug therapy ; Female ; Humans ; Lactobacillus/genetics/*physiology ; Mass Spectrometry/methods ; Metabolomics/*methods ; Microbiota/*drug effects ; Oligosaccharides/*analysis ; Prebiotics/*analysis ; RNA, Bacterial/analysis ; RNA, Ribosomal, 16S/analysis ; Sequence Analysis, RNA/methods ; Sugar Alcohols/*analysis ; Vagina/*microbiology ; }, abstract = {Perturbations to the vaginal microbiota can lead to dysbiosis, including bacterial vaginosis (BV), which affects a large portion of the female population. In a healthy state, the vaginal microbiota is characterized by low diversity and colonization by Lactobacillus spp., whereas in BV, these species are displaced by a highly diverse population of bacteria associated with adverse vaginal health outcomes. Since prebiotic ingestion has been a highly effective approach to invigorate lactobacilli for improved intestinal health, we hypothesized that these compounds could stimulate lactobacilli at the expense of BV organisms to maintain vaginal health. Monocultures of commensal Lactobacillus crispatus, Lactobacillus vaginalis, Lactobacillus gasseri, Lactobacillus johnsonii, Lactobacillus jensenii, and Lactobacillus iners, in addition to BV-associated organisms and Candida albicans, were tested for their ability to utilize a representative group of prebiotics consisting of lactitol, lactulose, raffinose, and oligofructose. The disaccharide lactulose was found to most broadly and specifically stimulate vaginal lactobacilli, including the strongly health-associated species L. crispatus, and importantly, not to stimulate BV organisms or C. albicans Using freshly collected vaginal samples, we showed that exposure to lactulose promoted commensal Lactobacillus growth and dominance and resulted in healthy acidity partially through lactic acid production. This provides support for further testing of lactulose to prevent dysbiosis and potentially to reduce the need for antimicrobial agents in managing vaginal health.IMPORTANCE Bacterial vaginosis (BV) and other dysbioses of the vaginal microbiota significantly affect the quality of life of millions of women. Antimicrobial therapy is often poorly effective, causes side effects, and does not prevent recurrences. We report one of very few studies that have evaluated how prebiotics-compounds that are selectively fermented by beneficial bacteria such as Lactobacillus spp.-can modulate the vaginal microbiota. We also report use of a novel in vitro polymicrobial model to study the impact of prebiotics on the vaginal microbiota. The identification of prebiotic lactulose as enhancing Lactobacillus growth but not that of BV organisms or Candida albicans has direct application for retention of homeostasis and prevention of vaginal dysbiosis and infection.}, }
@article {pmid29262868, year = {2017}, author = {Fenn, K and Strandwitz, P and Stewart, EJ and Dimise, E and Rubin, S and Gurubacharya, S and Clardy, J and Lewis, K}, title = {Quinones are growth factors for the human gut microbiota.}, journal = {Microbiome}, volume = {5}, number = {1}, pages = {161}, pmid = {29262868}, issn = {2049-2618}, support = {R01 AT009874/AT/NCCIH NIH HHS/United States ; R01 HG005824/HG/NHGRI NIH HHS/United States ; R01HG005824/NH/NIH HHS/United States ; R01GM086158/NH/NIH HHS/United States ; }, mesh = {Actinobacteria/drug effects/growth &amp; development ; Bacteria/*drug effects/*growth &amp; development ; Bacterial Physiological Phenomena/drug effects ; Bacteriological Techniques ; Coculture Techniques ; Escherichia coli/drug effects/growth &amp; development ; Faecalibacterium/drug effects/growth &amp; development ; Feces/microbiology ; Gastrointestinal Microbiome/*drug effects ; Humans ; Intercellular Signaling Peptides and Proteins/genetics/*pharmacology ; Phylogeny ; Siderophores/metabolism ; Ubiquinone/metabolism ; Vitamin K 2/*metabolism/pharmacology ; }, abstract = {BACKGROUND: The human gut microbiome has been linked to numerous components of health and disease. However, approximately 25% of the bacterial species in the gut remain uncultured, which limits our ability to properly understand, and exploit, the human microbiome. Previously, we found that growing environmental bacteria in situ in a diffusion chamber enables growth of uncultured species, suggesting the existence of growth factors in the natural environment not found in traditional cultivation media. One source of growth factors proved to be neighboring bacteria, and by using co-culture, we isolated previously uncultured organisms from the marine environment and identified siderophores as a major class of bacterial growth factors. Here, we employ similar co-culture techniques to grow bacteria from the human gut microbiome and identify novel growth factors.<br><br>RESULTS: By testing dependence of slow-growing colonies on faster-growing neighboring bacteria in a co-culture assay, eight taxonomically diverse pairs of bacteria were identified, in which an "induced" isolate formed a gradient of growth around a cultivatable "helper." This set included two novel species Faecalibacterium sp. KLE1255-belonging to the anti-inflammatory Faecalibacterium genus-and Sutterella sp. KLE1607. While multiple helper strains were identified, Escherichia coli was also capable of promoting growth of all induced isolates. Screening a knockout library of E. coli showed that a menaquinone biosynthesis pathway was required for growth induction of Faecalibacterium sp. KLE1255 and other induced isolates. Purified menaquinones induced growth of 7/8 of the isolated strains, quinone specificity profiles for individual bacteria were identified, and genome analysis suggests an incomplete menaquinone biosynthetic capability yet the presence of anaerobic terminal reductases in the induced strains, indicating an ability to respire anaerobically.<br><br>CONCLUSIONS: Our data show that menaquinones are a major class of growth factors for bacteria from the human gut microbiome. These organisms are taxonomically diverse, including members of the genus Faecalibacterium, Bacteroides, Bilophila, Gordonibacter, and Sutterella. This suggests that loss of quinone biosynthesis happened independently in many lineages of the human microbiota. Quinones can be used to improve existing bacterial growth media or modulate the human gut microbiota by encouraging the growth of important symbionts, such as Faecalibacterium species.}, }
@article {pmid29257783, year = {2018}, author = {Akrami, K and Sweeney, DA}, title = {The microbiome of the critically ill patient.}, journal = {Current opinion in critical care}, volume = {24}, number = {1}, pages = {49-54}, doi = {10.1097/MCC.0000000000000469}, pmid = {29257783}, issn = {1531-7072}, mesh = {Clostridium Infections/microbiology/therapy ; Colitis, Ulcerative/microbiology/therapy ; *Critical Illness/therapy ; Dysbiosis/etiology/*microbiology/therapy ; Fecal Microbiota Transplantation ; Humans ; Intensive Care Units ; Microbiota/*physiology ; Pneumonia, Ventilator-Associated/microbiology/therapy ; Probiotics/therapeutic use ; Treatment Outcome ; }, abstract = {PURPOSE OF REVIEW: Advances in the understanding of the human microbiome outside of the ICU have led investigators to consider the role of the microbiome in critical illness. The picture that is being elucidated is one of dysbiosis occurring at multiple sites in the critically ill patient. This review describes the changes that occur in the various microbiomes of a critically ill patient, the implications of these changes and shows how advances in the understanding of dysbiosis may lead to microbiome-targeted therapies.<br><br>RECENT FINDINGS: Critically ill patients undergo dysbiosis at several organ sites including the skin, gastrointestinal system and the lungs with loss of microbial diversity and a propensity for potentially pathogenic organisms to dominate a particular microbiome. These microbiome changes appear to be predictive of clinical outcome. While the use of fecal microbial transplantation has been demonstrated to be an effective treatment for recurrent Clostridium difficile infection, the use of fecal microbial transplantation and other microbiome modifying therapies may have a role in managing critical illness in the ICU.<br><br>SUMMARY: A growing understanding of the microbiome in the critically ill may modify current dogma regarding the pathogenesis of sepsis and other life-threatening conditions seen in the ICU, thereby fundamentally changing antibiotic stewardship and the management of the critically ill patient.}, }
@article {pmid29253074, year = {2018}, author = {Huang, L and Krüger, J and Sczyrba, A}, title = {Analyzing large scale genomic data on the cloud with Sparkhit.}, journal = {Bioinformatics (Oxford, England)}, volume = {34}, number = {9}, pages = {1457-1465}, pmid = {29253074}, issn = {1367-4811}, mesh = {Algorithms ; High-Throughput Nucleotide Sequencing/*methods ; Humans ; Metagenomics/*methods ; Microbiota/genetics ; Sequence Analysis, DNA/methods ; *Software ; }, abstract = {MOTIVATION: The increasing amount of next-generation sequencing data poses a fundamental challenge on large scale genomic analytics. Existing tools use different distributed computational platforms to scale-out bioinformatics workloads. However, the scalability of these tools is not efficient. Moreover, they have heavy run time overheads when pre-processing large amounts of data. To address these limitations, we have developed Sparkhit: a distributed bioinformatics framework built on top of the Apache Spark platform.<br><br>RESULTS: Sparkhit integrates a variety of analytical methods. It is implemented in the Spark extended MapReduce model. It runs 92-157 times faster than MetaSpark on metagenomic fragment recruitment and 18-32 times faster than Crossbow on data pre-processing. We analyzed 100 terabytes of data across four genomic projects in the cloud in 21&#x2009;h, which includes the run times of cluster deployment and data downloading. Furthermore, our application on the entire Human Microbiome Project shotgun sequencing data was completed in 2&#x2009;h, presenting an approach to easily associate large amounts of public datasets with reference data.<br><br>Sparkhit is freely available at: https://rhinempi.github.io/sparkhit/.<br><br>CONTACT: asczyrba@cebitec.uni-bielefeld.de.<br><br>SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.}, }
@article {pmid29242834, year = {2017}, author = {Usyk, M and Zolnik, CP and Patel, H and Levi, MH and Burk, RD}, title = {Novel ITS1 Fungal Primers for Characterization of the Mycobiome.}, journal = {mSphere}, volume = {2}, number = {6}, pages = {}, pmid = {29242834}, issn = {2379-5042}, support = {P30 DK041296/DK/NIDDK NIH HHS/United States ; P30 AI051519/AI/NIAID NIH HHS/United States ; R56 AI072204/AI/NIAID NIH HHS/United States ; K12 GM102779/GM/NIGMS NIH HHS/United States ; R01 CA078527/CA/NCI NIH HHS/United States ; R01 AI072204/AI/NIAID NIH HHS/United States ; U01 CA078527/CA/NCI NIH HHS/United States ; P30 CA013330/CA/NCI NIH HHS/United States ; }, abstract = {Studies of the human microbiome frequently omit characterization of fungal communities (the mycobiome), which limits our ability to investigate how fungal communities influence human health. The internal transcribed spacer 1 (ITS1) region of the eukaryotic ribosomal cluster has features allowing for wide taxonomic coverage and has been recognized as a suitable barcode region for species-level identification of fungal organisms. We developed custom ITS1 primer sets using iterative alignment refinement. Primer performance was evaluated using in silico testing and experimental testing of fungal cultures and human samples. Using an expanded novel reference database, SIS (18S-ITS1-5.8S), the newly designed primers showed an average in silico taxonomic coverage of 79.9% ± 7.1% compared to a coverage of 44.6% ± 13.2% using previously published primers (P = 0.05). The newly described primer sets recovered an average of 21,830 ± 225 fungal reads from fungal isolate culture samples, whereas the previously published primers had an average of 3,305 ± 1,621 reads (P = 0.03). Of note was an increase in the taxonomic coverage of the Candida genus, which went from a mean coverage of 59.5% ± 13% to 100.0% ± 0.0% (P = 0.0015) comparing the previously described primers to the new primers, respectively. The newly developed ITS1 primer sets significantly improve general taxonomic coverage of fungal communities infecting humans and increased read depth by an order of magnitude over the best-performing published primer set tested. The overall best-performing primer pair in terms of taxonomic coverage and read recovery, ITS1-30F/ITS1-217R, will aid in advancing research in the area of the human mycobiome. IMPORTANCE The mycobiome constitutes all the fungal organisms within an environment or biological niche. The fungi are eukaryotes, are extremely heterogeneous, and include yeasts and molds that colonize humans as part of the microbiome. In addition, fungi can also infect humans and cause disease. Characterization of the bacterial component of the microbiome was revolutionized by 16S rRNA gene fragment amplification, next-generation sequencing technologies, and bioinformatics pipelines. Characterization of the mycobiome has often not been included in microbiome studies because of limitations in amplification systems. This report revisited the selection of PCR primers that amplify the fungal ITS1 region. We have identified primers with superior identification of fungi present in the database. We have compared the new primer sets against those previously used in the literature and show a significant improvement in read count and taxon identification. These primers should facilitate the study of fungi in human physiology and disease states.}, }
@article {pmid29232932, year = {2017}, author = {Vitetta, L and Saltzman, ET and Thomsen, M and Nikov, T and Hall, S}, title = {Adjuvant Probiotics and the Intestinal Microbiome: Enhancing Vaccines and Immunotherapy Outcomes.}, journal = {Vaccines}, volume = {5}, number = {4}, pages = {}, pmid = {29232932}, issn = {2076-393X}, abstract = {Immune defence against pathogenic agents comprises the basic premise for the administration of vaccines. Vaccinations have hence prevented millions of infectious illnesses, hospitalizations and mortality. Acquired immunity comprises antibody and cell mediated responses and is characterized by its specificity and memory. Along a similar congruent yet diverse mode of disease prevention, the human host has negotiated from in utero and at birth with the intestinal commensal bacterial cohort to maintain local homeostasis in order to achieve immunological tolerance in the new born. The advent of the Human Microbiome Project has redefined an appreciation of the interactions between the host and bacteria in the intestines from one of a collection of toxic waste to one of a symbiotic existence. Probiotics comprise bacterial genera thought to provide a health benefit to the host. The intestinal microbiota has profound effects on local and extra-intestinal end organ physiology. As such, we further posit that the adjuvant administration of dedicated probiotic formulations can encourage the intestinal commensal cohort to beneficially participate in the intestinal microbiome-intestinal epithelia-innate-cell mediated immunity axes and cell mediated cellular immunity with vaccines aimed at preventing infectious diseases whilst conserving immunological tolerance. The strength of evidence for the positive effect of probiotic administration on acquired immune responses has come from various studies with viral and bacterial vaccines. We posit that the introduction early of probiotics may provide significant beneficial immune outcomes in neonates prior to commencing a vaccination schedule or in elderly adults prior to the administration of vaccinations against influenza viruses.}, }
@article {pmid29232848, year = {2017}, author = {Vernocchi, P and Del Chierico, F and Quagliariello, A and Ercolini, D and Lucidi, V and Putignani, L}, title = {A Metagenomic and in Silico Functional Prediction of Gut Microbiota Profiles May Concur in Discovering New Cystic Fibrosis Patient-Targeted Probiotics.}, journal = {Nutrients}, volume = {9}, number = {12}, pages = {}, pmid = {29232848}, issn = {2072-6643}, mesh = {Bacteria/*genetics ; Case-Control Studies ; Child, Preschool ; Cystic Fibrosis/*microbiology ; Feces/microbiology ; Female ; *Gastrointestinal Microbiome ; Humans ; Male ; Metagenomics/*methods ; Phylogeny ; *Probiotics ; RNA, Ribosomal, 16S/analysis ; }, abstract = {Cystic fibrosis (CF) is a life-limiting hereditary disorder that results in aberrant mucosa in the lungs and digestive tract, chronic respiratory infections, chronic inflammation, and the need for repeated antibiotic treatments. Probiotics have been demonstrated to improve the quality of life of CF patients. We investigated the distribution of gut microbiota (GM) bacteria to identify new potential probiotics for CF patients on the basis of GM patterns. Fecal samples of 28 CF patients and 31 healthy controls (HC) were collected and analyzed by 16S rRNA-based pyrosequencing analysis of GM, to produce CF-HC paired maps of the distribution of operational taxonomic units (OTUs), and by Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) for Kyoto Encyclopedia of Genes and Genomes (KEGG) biomarker prediction. The maps were scanned to highlight the distribution of bacteria commonly claimed as probiotics, such as bifidobacteria and lactobacilli, and of butyrate-producing colon bacteria, such as Eubacterium spp. and Faecalibacterium prausnitzii. The analyses highlighted 24 OTUs eligible as putative probiotics. Eleven and nine species were prevalently associated with the GM of CF and HC subjects, respectively. Their KEGG prediction provided differential CF and HC pathways, indeed associated with health-promoting biochemical activities in the latter case. GM profiling and KEGG biomarkers concurred in the evaluation of nine bacterial species as novel putative probiotics that could be investigated for the nutritional management of CF patients.}, }
@article {pmid29227922, year = {2018}, author = {Gao, W and Howden, BP and Stinear, TP}, title = {Evolution of virulence in Enterococcus faecium, a hospital-adapted opportunistic pathogen.}, journal = {Current opinion in microbiology}, volume = {41}, number = {}, pages = {76-82}, doi = {10.1016/j.mib.2017.11.030}, pmid = {29227922}, issn = {1879-0364}, mesh = {Anti-Bacterial Agents/pharmacology ; Cross Infection/immunology/*microbiology ; Drug Resistance, Bacterial/genetics/immunology ; Enterococcus faecium/drug effects/*genetics/immunology/*pathogenicity ; *Evolution, Molecular ; Genome, Bacterial ; Gram-Positive Bacterial Infections/*microbiology ; Humans ; Microbial Sensitivity Tests ; Virulence ; Virulence Factors ; }, abstract = {Enterococci are long-standing members of the human microbiome and they are also widely distributed in nature. However, with the surge of antibiotic-resistance in recent decades, two enterococcal species (Enterococcus faecalis and Enterococcus faecium) have emerged to become significant nosocomial pathogens, acquiring extensive antibiotic resistance. In this review, we summarize what is known about the evolution of virulence in E. faecium, highlighting a specific clone of E. faecium called ST796 that has emerged recently and spread globally.}, }
@article {pmid29227468, year = {2018}, author = {Beaulaurier, J and Zhu, S and Deikus, G and Mogno, I and Zhang, XS and Davis-Richardson, A and Canepa, R and Triplett, EW and Faith, JJ and Sebra, R and Schadt, EE and Fang, G}, title = {Metagenomic binning and association of plasmids with bacterial host genomes using DNA methylation.}, journal = {Nature biotechnology}, volume = {36}, number = {1}, pages = {61-69}, pmid = {29227468}, issn = {1546-1696}, support = {R01 GM114472/GM/NIGMS NIH HHS/United States ; }, mesh = {Algorithms ; Bacteria/genetics ; Cluster Analysis ; DNA Methylation/*genetics ; Environmental Microbiology ; Genome, Bacterial/genetics ; Humans ; Metagenome/*genetics ; *Metagenomics ; Microbiota/*genetics ; Plasmids/genetics ; Sequence Analysis, DNA ; }, abstract = {Shotgun metagenomics methods enable characterization of microbial communities in human microbiome and environmental samples. Assembly of metagenome sequences does not output whole genomes, so computational binning methods have been developed to cluster sequences into genome 'bins'. These methods exploit sequence composition, species abundance, or chromosome organization but cannot fully distinguish closely related species and strains. We present a binning method that incorporates bacterial DNA methylation signatures, which are detected using single-molecule real-time sequencing. Our method takes advantage of these endogenous epigenetic barcodes to resolve individual reads and assembled contigs into species- and strain-level bins. We validate our method using synthetic and real microbiome sequences. In addition to genome binning, we show that our method links plasmids and other mobile genetic elements to their host species in a real microbiome sample. Incorporation of DNA methylation information into shotgun metagenomics analyses will complement existing methods to enable more accurate sequence binning.}, }
@article {pmid29221589, year = {2017}, author = {Lebaron, P and Bourrain, M}, title = {[Not Available].}, journal = {Annales de dermatologie et de venereologie}, volume = {144 Suppl 1}, number = {}, pages = {S35-S41}, doi = {10.1016/S0151-9638(17)31041-4}, pmid = {29221589}, issn = {0151-9638}, mesh = {Bacterial Typing Techniques/methods ; Balneology ; Dermatitis, Atopic/microbiology ; Ecosystem ; Health Resorts ; Humans ; Microbial Interactions ; *Microbiota/drug effects ; Mineral Waters/therapeutic use ; Nutrients/metabolism ; Skin/*microbiology ; Skin Diseases/microbiology/therapy ; Vitamins/metabolism ; }, abstract = {Human hosts a large number of microorganisms that constitute its microbiome and the vast majority of them are very useful and even essentials. The human microbiome is a complex ecosystem where live populations of transient or resident microorganisms. The process of co-development or co-adaptation played a major role in the establishment of indigenous communities and help explain the dominance of positive interactions (commensal, symbiotic or mutualistic) in the human-microorganism relationship. The assimilation of nutrients, production of anti-inflammatory compounds, defense against pathogens, vitamin production or stimulating the immune system are some of the key benefits of the indigenous microorganisms. Understanding the skin microbiome opens new exploratory fields and represents a real challenge for both the academic knowledge and the development of new therapeutic approaches.}, }
@article {pmid29211710, year = {2017}, author = {Surana, NK and Kasper, DL}, title = {Moving beyond microbiome-wide associations to causal microbe identification.}, journal = {Nature}, volume = {552}, number = {7684}, pages = {244-247}, pmid = {29211710}, issn = {1476-4687}, support = {K08 AI108690/AI/NIAID NIH HHS/United States ; U19 AI109764/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Body Weight ; Cell Survival ; Clostridium/genetics/*isolation &amp; purification/*physiology ; Colitis/*microbiology/*prevention &amp; control ; Feces/microbiology ; *Gastrointestinal Microbiome/genetics ; Germ-Free Life ; Intestinal Mucosa/metabolism ; Intestines/microbiology ; Limosilactobacillus reuteri/genetics/physiology ; Mice ; Pancreatitis-Associated Proteins/metabolism ; *Phenotype ; Ruminococcus/genetics/physiology ; Symbiosis ; }, abstract = {Microbiome-wide association studies have established that numerous diseases are associated with changes in the microbiota. These studies typically generate a long list of commensals implicated as biomarkers of disease, with no clear relevance to disease pathogenesis. If the field is to move beyond correlations and begin to address causation, an effective system is needed for refining this catalogue of differentially abundant microbes and to allow subsequent mechanistic studies. Here we demonstrate that triangulation of microbe-phenotype relationships is an effective method for reducing the noise inherent in microbiota studies and enabling identification of causal microbes. We found that gnotobiotic mice harbouring different microbial communities exhibited differential survival in a colitis model. Co-housing of these mice generated animals that had hybrid microbiotas and displayed intermediate susceptibility to colitis. Mapping of microbe-phenotype relationships in parental mouse strains and in mice with hybrid microbiotas identified the bacterial family Lachnospiraceae as a correlate for protection from disease. Using directed microbial culture techniques, we discovered Clostridium immunis, a previously unknown bacterial species from this family, that-when administered to colitis-prone mice-protected them against colitis-associated death. To demonstrate the generalizability of our approach, we used it to identify several commensal organisms that induce intestinal expression of an antimicrobial peptide. Thus, we have used microbe-phenotype triangulation to move beyond the standard correlative microbiome study and identify causal microbes for two completely distinct phenotypes. Identification of disease-modulating commensals by microbe-phenotype triangulation may be more broadly applicable to human microbiome studies.}, }
@article {pmid29209090, year = {2017}, author = {Duvallet, C and Gibbons, SM and Gurry, T and Irizarry, RA and Alm, EJ}, title = {Meta-analysis of gut microbiome studies identifies disease-specific and shared responses.}, journal = {Nature communications}, volume = {8}, number = {1}, pages = {1784}, pmid = {29209090}, issn = {2041-1723}, support = {P30 DK043351/DK/NIDDK NIH HHS/United States ; }, mesh = {Bacteria/classification/*growth &amp; development ; Case-Control Studies ; Feces/microbiology ; Gastrointestinal Diseases/*microbiology ; *Gastrointestinal Microbiome ; Gastrointestinal Tract/*microbiology ; Humans ; Population Density ; Population Dynamics ; }, abstract = {Hundreds of clinical studies have demonstrated associations between the human microbiome and disease, yet fundamental questions remain on how we can generalize this knowledge. Results from individual studies can be inconsistent, and comparing published data is further complicated by a lack of standard processing and analysis methods. Here we introduce the MicrobiomeHD database, which includes 28 published case-control gut microbiome studies spanning ten diseases. We perform a cross-disease meta-analysis of these studies using standardized methods. We find consistent patterns characterizing disease-associated microbiome changes. Some diseases are associated with over 50 genera, while most show only 10-15 genus-level changes. Some diseases are marked by the presence of potentially pathogenic microbes, whereas others are characterized by a depletion of health-associated bacteria. Furthermore, we show that about half of genera associated with individual studies are bacteria that respond to more than one disease. Thus, many associations found in case-control studies are likely not disease-specific but rather part of a non-specific, shared response to health and disease.}, }
@article {pmid29202045, year = {2017}, author = {Mortimer, TD and Annis, DS and O'Neill, MB and Bohr, LL and Smith, TM and Poinar, HN and Mosher, DF and Pepperell, CS}, title = {Adaptation in a Fibronectin Binding Autolysin of Staphylococcus saprophyticus.}, journal = {mSphere}, volume = {2}, number = {6}, pages = {}, pmid = {29202045}, issn = {2379-5042}, support = {R01 AI113287/AI/NIAID NIH HHS/United States ; T32 GM007215/GM/NIGMS NIH HHS/United States ; }, abstract = {Human-pathogenic bacteria are found in a variety of niches, including free-living, zoonotic, and microbiome environments. Identifying bacterial adaptations that enable invasive disease is an important means of gaining insight into the molecular basis of pathogenesis and understanding pathogen emergence. Staphylococcus saprophyticus, a leading cause of urinary tract infections, can be found in the environment, food, animals, and the human microbiome. We identified a selective sweep in the gene encoding the Aas adhesin, a key virulence factor that binds host fibronectin. We hypothesize that the mutation under selection (aas_2206A>C) facilitates colonization of the urinary tract, an environment where bacteria are subject to strong shearing forces. The mutation appears to have enabled emergence and expansion of a human-pathogenic lineage of S. saprophyticus. These results demonstrate the power of evolutionary genomic approaches in discovering the genetic basis of virulence and emphasize the pleiotropy and adaptability of bacteria occupying diverse niches. IMPORTANCEStaphylococcus saprophyticus is an important cause of urinary tract infections (UTI) in women; such UTI are common, can be severe, and are associated with significant impacts to public health. In addition to being a cause of human UTI, S. saprophyticus can be found in the environment, in food, and associated with animals. After discovering that UTI strains of S. saprophyticus are for the most part closely related to each other, we sought to determine whether these strains are specially adapted to cause disease in humans. We found evidence suggesting that a mutation in the gene aas is advantageous in the context of human infection. We hypothesize that the mutation allows S. saprophyticus to survive better in the human urinary tract. These results show how bacteria found in the environment can evolve to cause disease.}, }
@article {pmid29197615, year = {2018}, author = {Mao, Q and Jiang, F and Yin, R and Wang, J and Xia, W and Dong, G and Ma, W and Yang, Y and Xu, L and Hu, J}, title = {Interplay between the lung microbiome and lung cancer.}, journal = {Cancer letters}, volume = {415}, number = {}, pages = {40-48}, doi = {10.1016/j.canlet.2017.11.036}, pmid = {29197615}, issn = {1872-7980}, mesh = {Cell Transformation, Neoplastic ; Dysbiosis/*microbiology/therapy ; Host-Pathogen Interactions ; Humans ; Lung/*microbiology ; Lung Neoplasms/*microbiology/therapy ; *Microbiota ; }, abstract = {The human microbiome confers benefits or disease susceptibility to the human body through multiple pathways. Disruption of the symbiotic balance of the human microbiome is commonly found in systematic diseases such as diabetes, obesity, and chronic gastric diseases. Emerging evidence has suggested that dysbiosis of the microbiota may also play vital roles in carcinogenesis at multiple levels, e.g., by affecting metabolic, inflammatory, or immune pathways. Although the impact of the gut microbiome on the digestive cancer has been widely explored, few studies have investigated the interplay between the microbiome and lung cancer. Some recent studies have shown that certain microbes and microbiota dysbiosis are correlated with development of lung cancer. In this mini-review, we briefly summarize current research findings describing the relationship between the lung microbiome and lung cancer. We further discuss the potential mechanisms through which the lung microbiome may play a role in lung carcinogenesis and impact lung cancer treatment. A better knowledge of the interplay between the lung microbiome and lung cancer may promote the development of innovative strategies for early prevention and personalized treatment in lung cancer.}, }
@article {pmid29196353, year = {2017}, author = {Moffatt, MF and Cookson, WO}, title = {The lung microbiome in health and disease.}, journal = {Clinical medicine (London, England)}, volume = {17}, number = {6}, pages = {525-529}, pmid = {29196353}, issn = {1473-4893}, mesh = {Asthma/microbiology ; Bronchiectasis/microbiology ; Cystic Fibrosis/microbiology ; Humans ; Lung/*microbiology ; Lung Diseases/*microbiology ; Metagenomics ; *Microbiota/genetics ; Pulmonary Disease, Chronic Obstructive/microbiology ; RNA, Ribosomal, 16S/genetics ; }, abstract = {The Human Microbiome Project began 10 years ago, leading to a significant growth in understanding of the role the human microbiome plays in health and disease. In this article, we explain with an emphasis on the lung, the origins of microbiome research. We discuss how 16S rRNA gene sequencing became the first major molecular tool to examine the bacterial communities present within the human body. We highlight the pitfalls of molecular-based studies, such as false findings resulting from contamination, and the limitations of 16S rRNA gene sequencing. Knowledge about the lung microbiome has evolved from initial scepticism to the realisation that it might have a significant influence on many illnesses. We also discuss the lung microbiome in the context of disease by giving examples of important respiratory conditions. In addition, we draw attention to the challenges for metagenomic studies of respiratory samples and the importance of systematic bacterial isolation to enable host-microbiome interactions to be understood. We conclude by discussing how knowledge of the lung microbiome impacts current clinical diagnostics.}, }
@article {pmid29183332, year = {2017}, author = {Hall, AB and Yassour, M and Sauk, J and Garner, A and Jiang, X and Arthur, T and Lagoudas, GK and Vatanen, T and Fornelos, N and Wilson, R and Bertha, M and Cohen, M and Garber, J and Khalili, H and Gevers, D and Ananthakrishnan, AN and Kugathasan, S and Lander, ES and Blainey, P and Vlamakis, H and Xavier, RJ and Huttenhower, C}, title = {A novel Ruminococcus gnavus clade enriched in inflammatory bowel disease patients.}, journal = {Genome medicine}, volume = {9}, number = {1}, pages = {103}, pmid = {29183332}, issn = {1756-994X}, support = {U54 DK102557/DK/NIDDK NIH HHS/United States ; U54DE023798//National Institutes of Health (US)/ ; P30 DK043351/DK/NIDDK NIH HHS/United States ; P30DK43351//National Institute of Diabetes and Digestive and Kidney Diseases/ ; R01 DK092405/DK/NIDDK NIH HHS/United States ; U54 DE023798/DE/NIDCR NIH HHS/United States ; K99 DK113224/DK/NIDDK NIH HHS/United States ; R01DK92405//National Institute of Diabetes and Digestive and Kidney Diseases/ ; MCB-1453942//National Science Foundation (US)/ ; }, mesh = {Adult ; Aged ; Feces/microbiology ; Gastrointestinal Microbiome/genetics ; Genome, Bacterial ; Humans ; Inflammatory Bowel Diseases/*microbiology ; Middle Aged ; Oxidative Stress ; Phylogeny ; Ruminococcus/genetics/*isolation &amp; purification ; Species Specificity ; Young Adult ; }, abstract = {BACKGROUND: Inflammatory bowel disease (IBD) is characterized by chronic inflammation of the gastrointestinal tract that is associated with changes in the gut microbiome. Here, we sought to identify strain-specific functional correlates with IBD outcomes.<br><br>METHODS: We performed metagenomic sequencing of monthly stool samples from 20 IBD patients and 12 controls (266 total samples). These were taxonomically profiled with MetaPhlAn2 and functionally profiled using HUMAnN2. Differentially abundant species were identified using MaAsLin and strain-specific pangenome haplotypes were analyzed using PanPhlAn.<br><br>RESULTS: We found a significantly higher abundance in patients of facultative anaerobes that can tolerate the increased oxidative stress of the IBD gut. We also detected dramatic, yet transient, blooms of Ruminococcus gnavus in IBD patients, often co-occurring with increased disease activity. We identified two distinct clades of R. gnavus strains, one of which is enriched in IBD patients. To study functional differences between these two clades, we augmented the R. gnavus pangenome by sequencing nine isolates from IBD patients. We identified 199 IBD-specific, strain-specific genes involved in oxidative stress responses, adhesion, iron-acquisition, and mucus utilization, potentially conferring an adaptive advantage for this R. gnavus clade in the IBD gut.<br><br>CONCLUSIONS: This study adds further evidence to the hypothesis that increased oxidative stress may be a major factor shaping the dysbiosis of the microbiome observed in IBD and suggests that R. gnavus may be an important member of the altered gut community in IBD.}, }
@article {pmid29178920, year = {2017}, author = {Nash, AK and Auchtung, TA and Wong, MC and Smith, DP and Gesell, JR and Ross, MC and Stewart, CJ and Metcalf, GA and Muzny, DM and Gibbs, RA and Ajami, NJ and Petrosino, JF}, title = {The gut mycobiome of the Human Microbiome Project healthy cohort.}, journal = {Microbiome}, volume = {5}, number = {1}, pages = {153}, pmid = {29178920}, issn = {2049-2618}, support = {P30 DK056338/DK/NIDDK NIH HHS/United States ; U54 HG003273/HG/NHGRI NIH HHS/United States ; 2 U54 HG003273//National Human Genome Research Institute/ ; }, mesh = {Candida/classification/genetics/isolation &amp; purification ; Cohort Studies ; DNA, Ribosomal Spacer/genetics ; Feces/microbiology ; Fungi/classification/genetics/*isolation &amp; purification ; Gastrointestinal Microbiome/*genetics ; Genetic Variation ; *Healthy Volunteers ; High-Throughput Nucleotide Sequencing/methods ; Humans ; Malassezia/classification/genetics/isolation &amp; purification ; Metagenomics/methods ; *Microbiota ; *Mycobiome ; RNA, Ribosomal, 18S/genetics ; Saccharomyces/classification/genetics/isolation &amp; purification ; Sequence Analysis, DNA ; }, abstract = {BACKGROUND: Most studies describing the human gut microbiome in healthy and diseased states have emphasized the bacterial component, but the fungal microbiome (i.e., the mycobiome) is beginning to gain recognition as a fundamental part of our microbiome. To date, human gut mycobiome studies have primarily been disease centric or in small cohorts of healthy individuals. To contribute to existing knowledge of the human mycobiome, we investigated the gut mycobiome of the Human Microbiome Project (HMP) cohort by sequencing the Internal Transcribed Spacer 2 (ITS2) region as well as the 18S rRNA gene.<br><br>RESULTS: Three hundred seventeen HMP stool samples were analyzed by ITS2 sequencing. Fecal fungal diversity was significantly lower in comparison to bacterial diversity. Yeast dominated the samples, comprising eight of the top 15 most abundant genera. Specifically, fungal communities were characterized by a high prevalence of Saccharomyces, Malassezia, and Candida, with S. cerevisiae, M. restricta, and C. albicans operational taxonomic units (OTUs) present in 96.8, 88.3, and 80.8% of samples, respectively. There was a high degree of inter- and intra-volunteer variability in fungal communities. However, S. cerevisiae, M. restricta, and C. albicans OTUs were found in 92.2, 78.3, and 63.6% of volunteers, respectively, in all samples donated over an approximately 1-year period. Metagenomic and 18S rRNA gene sequencing data agreed with ITS2 results; however, ITS2 sequencing provided greater resolution of the relatively low abundance mycobiome constituents.<br><br>CONCLUSIONS: Compared to bacterial communities, the human gut mycobiome is low in diversity and dominated by yeast including Saccharomyces, Malassezia, and Candida. Both inter- and intra-volunteer variability in the HMP cohort were high, revealing that unlike bacterial communities, an individual's mycobiome is no more similar to itself over time than to another person's. Nonetheless, several fungal species persisted across a majority of samples, evidence that a core gut mycobiome may exist. ITS2 sequencing data provided greater resolution of the mycobiome membership compared to metagenomic and 18S rRNA gene sequencing data, suggesting that it is a more sensitive method for studying the mycobiome of stool samples.}, }
@article {pmid29177119, year = {2017}, author = {Wilantho, A and Deekaew, P and Srisuttiyakorn, C and Tongsima, S and Somboonna, N}, title = {Diversity of bacterial communities on the facial skin of different age-group Thai males.}, journal = {PeerJ}, volume = {5}, number = {}, pages = {e4084}, pmid = {29177119}, issn = {2167-8359}, abstract = {BACKGROUND: Skin microbiome varies from person to person due to a combination of various factors, including age, biogeography, sex, cosmetics and genetics. Many skin disorders appear to be related to the resident microflora, yet databases of facial skin microbiome of many biogeographies, including Thai, are limited.<br><br>METHODS: Metagenomics derived B-RISA and 16S rRNA gene sequencing was utilized to identify the culture-independent bacterial diversity on Thai male faces (cheek and forehead areas). Skin samples were categorized (grouped) into (i) normal (teenage.hea) and (ii) acne-prone (teenage.acn) young adults, and normal (iii) middle-aged (middle.hea) and (iv) elderly (elderly.hea) adults.<br><br>RESULTS: The 16S rRNA gene sequencing was successful as the sequencing depth had an estimated >98% genus coverage of the true community. The major diversity was found between the young and elderly adults in both cheek and forehead areas, followed by that between normal and acne young adults. Detection of representative characteristics indicated that bacteria from the order Rhizobiales, genera Sphingomonas and Pseudoalteromonas, distinguished the elderly.hea microbiota, along the clinical features of wrinkles and pores. Prediction of the metabolic potential revealed reduced metabolic pathways involved in replication and repair, nucleotide metabolism and genetic translation in the elderly.hea compared with that in the teenage.hea. For young adults, some unique compositions such as abundance of Propionibacterium acnes and Staphylococcus epidermidis, with a minor diversity between normal and acne skins, were detected. The metabolic potentials of the acne vs. normal young adults showed that teenage.acn was low in many cellular processes (e.g., cell motility and environmental adaptation), but high in carbohydrate metabolism, which could support acne growth. Moreover, comparison with the age-matched males from the US (Boulder, Colorado) to gain insight into the diversity across national biogeography, revealed differences in the distribution pattern of species, although common bacteria were present in both biogeographical samples. Furthermore, B-RISA served as a crosscheck result to the 16S rRNA gene sequencing (i.e., differences between teenage and elderly microbiota).<br><br>CONCLUSIONS: This study revealed and compared the microbial diversity on different aged Thai male faces, and included analyses for representing the bacterial flora, the clinical skin characteristics, and comparison with the US age-matched. The results represent the first skin microbiota of Thai males, and helps the design of a large-scale skin microbiome study of Thais. The findings of the diversity among ages, skin type and national biogeography supported the importance of these traits in the skin microbiome and in developing a safe and sustainable treatment for acne and aging skin diseases.}, }
@article {pmid29175577, year = {2018}, author = {McMillan, A and Renaud, JB and Burgess, KMN and Orimadegun, AE and Akinyinka, OO and Allen, SJ and Miller, JD and Reid, G and Sumarah, MW}, title = {Aflatoxin exposure in Nigerian children with severe acute malnutrition.}, journal = {Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association}, volume = {111}, number = {}, pages = {356-362}, doi = {10.1016/j.fct.2017.11.030}, pmid = {29175577}, issn = {1873-6351}, mesh = {Aflatoxins/administration &amp; dosage/chemistry/*toxicity ; Child Nutrition Disorders/blood/*complications/*epidemiology ; Child, Preschool ; Humans ; Infant ; Molecular Structure ; Nigeria ; }, abstract = {Aflatoxin exposure is an important public health concern in sub-Saharan Africa as well as parts of Latin America and Asia. In addition to hepatocellular carcinoma, chronic aflatoxin exposure is believed to play a role in childhood growth impairment. The most reliable biomarker of chronic aflatoxin exposure is the aflatoxin-albumin adduct, as measured by ELISA or isotope dilution mass spectrometry (IDMS). In this report, we have used high resolution LC-MS/MS with IDMS to quantitate AFB1-lysine in an extremely vulnerable population of Nigerian children suffering from severe acute malnutrition. To increase the sensitivity and reliability of the analyses, a labelled AFB1-[13]C6[15]N2-lysine internal standard was synthesized. AFB1-lysine concentrations in this population ranged between 0.2 and 59.2 pg/mg albumin, with a median value of 2.6 pg/mg albumin. AFB1-lysine concentrations were significantly higher in stunted children (median = 4.6 pg/mg) compared to non-stunted (1.2 pg/mg), as well as in children with severe acute malnutrition (4.3 pg/mg) compared to controls (0.8 pg/mg). The median concentrations were also higher in children with kwashiorkor (6.3 pg/mg) compared to those suffering from marasmus (0.9 pg/mg). This is the first report of the use of high-resolution mass spectrometry to quantitate AFB1-lysine in humans.}, }
@article {pmid29155236, year = {2018}, author = {Al, KF and Bisanz, JE and Gloor, GB and Reid, G and Burton, JP}, title = {Evaluation of sampling and storage procedures on preserving the community structure of stool microbiota: A simple at-home toilet-paper collection method.}, journal = {Journal of microbiological methods}, volume = {144}, number = {}, pages = {117-121}, doi = {10.1016/j.mimet.2017.11.014}, pmid = {29155236}, issn = {1872-8359}, mesh = {*Bathroom Equipment ; DNA, Bacterial ; Feces/*microbiology ; *Gastrointestinal Microbiome/genetics ; Humans ; Pilot Projects ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; Specimen Handling/*methods ; Temperature ; Volunteers ; }, abstract = {BACKGROUND: The increasing interest on the impact of the gut microbiota on health and disease has resulted in multiple human microbiome-related studies emerging. However, multiple sampling methods are being used, making cross-comparison of results difficult. To avoid additional clinic visits and increase patient recruitment to these studies, there is the potential to utilize at-home stool sampling. The aim of this pilot study was to compare simple self-sampling collection and storage methods.<br><br>METHODS: To simulate storage conditions, stool samples from three volunteers were freshly collected, placed on toilet tissue, and stored at four temperatures (-80, 7, 22 and 37&#xb0;C), either dry or in the presence of a stabilization agent (RNAlater&#xae;) for 3 or 7days. Using 16S rRNA gene sequencing by Illumina, the effect of storage variations for each sample was compared to a reference community from fresh, unstored counterparts. Fastq files may be accessed in the NCBI Sequence Read Archive: Bioproject ID PRJNA418287.<br><br>RESULTS: Microbial diversity and composition were not significantly altered by any storage method. Samples were always separable based on participant, regardless of storage method suggesting there was no need for sample preservation by a stabilization agent.<br><br>DISCUSSION: In summary, if immediate sample processing is not feasible, short term storage of unpreserved stool samples on toilet paper offers a reliable way to assess the microbiota composition by 16S rRNA gene sequencing.}, }
@article {pmid29152585, year = {2017}, author = {d'Hennezel, E and Abubucker, S and Murphy, LO and Cullen, TW}, title = {Total Lipopolysaccharide from the Human Gut Microbiome Silences Toll-Like Receptor Signaling.}, journal = {mSystems}, volume = {2}, number = {6}, pages = {}, pmid = {29152585}, issn = {2379-5077}, abstract = {Cohabitation of microbial communities with the host enables the formation of a symbiotic relationship that maintains homeostasis in the gut and beyond. One prevailing model suggests that this relationship relies on the capacity of host cells and tissues to remain tolerant to the strong immune stimulation generated by the microbiota such as the activation of Toll-like receptor 4 (TLR4) pathways by lipopolysaccharide (LPS). Indeed, gut microbial LPS is thought to be one of the most potent activators of innate immune signaling and an important mediator of the microbiome's influence on host physiology. In this study, we performed computational and experimental analyses of healthy human fecal samples to examine the TLR4 signaling capacity of the gut microbiota. These analyses revealed that an immunoinhibitory activity of LPS, conserved across the members of the order Bacteroidales and derived from an underacylated structural feature, silences TLR4 signaling for the entire consortium of organisms inhabiting the human gut. Comparative analysis of metagenomic data from the Human Microbiome Project and healthy-donor samples indicates that immune silencing via LPS is a microbe-intrinsic feature in all healthy adults. These findings challenge the current belief that robust TLR4 signaling is a feature of the microbiome and demonstrate that microbiome-derived LPS has the ability to facilitate host tolerance of gut microbes. These findings have broad implications for how we model host-microbe interactions and for our understanding of microbiome-linked disease. IMPORTANCE While the ability for humans to host a complex microbial ecosystem is an essential property of life, the mechanisms allowing for immune tolerance of such a large microbial load are not completely understood and are currently the focus of intense research. This study shows that an important proinflammatory pathway that is commonly triggered by pathogenic bacteria upon interaction with the host is, in fact, actively repressed by the bacteria of the gut microbiome, supporting the idea that beneficial microbes themselves contribute to the immune tolerance in support of homeostasis. These findings are important for two reasons. First, many currently assume that proinflammatory signaling by lipopolysaccharide is a fundamental feature of the gut flora. This assumption influences greatly how host-microbiome interactions are theoretically modeled but also how they are experimentally studied, by using robust TLR signaling conditions to simulate commensals. Second, elucidation of the mechanisms that support host-microbe tolerance is key to the development of therapeutics for both intestinal and systemic inflammatory disorders.}, }
@article {pmid29152409, year = {2017}, author = {Tosi, L and Sridhara, V and Yang, Y and Guan, D and Shpilker, P and Segata, N and Larman, HB and Parekkadan, B}, title = {Long-adapter single-strand oligonucleotide probes for the massively multiplexed cloning of kilobase genome regions.}, journal = {Nature biomedical engineering}, volume = {1}, number = {}, pages = {}, pmid = {29152409}, issn = {2157-846X}, support = {K01 DK087770/DK/NIDDK NIH HHS/United States ; R01 EB012521/EB/NIBIB NIH HHS/United States ; R21 CA202875/CA/NCI NIH HHS/United States ; U24 AI118633/AI/NIAID NIH HHS/United States ; }, abstract = {As the catalogue of sequenced genomes and metagenomes continues to grow, massively parallel approaches for the comprehensive and functional analysis of gene products and regulatory elements are becoming increasingly valuable. Current strategies to synthesize or clone complex libraries of DNA sequences are limited by the length of the DNA targets, throughput and cost. Here, we show that long-adapter single-strand oligonucleotide (LASSO) probes can capture and clone thousands of kilobase DNA fragments in a single reaction. As a proof-of-principle, we simultaneously cloned >3,000 bacterial open reading frames (ORFs) from E. coli genomic DNA (spanning 400-5,000 bp targets). Targets were enriched up to a median of ~60-fold compared to non-targeted genomic regions. At a cutoff of 3 times the median non-target reads per kilobase of genetic element per million reads, ~75% of the targeted ORFs were successfully captured. We also show that LASSO probes can clone human ORFs from complementary DNA, and an ORF library from a human-microbiome sample. LASSO probes could be used for the preparation of long-read sequencing libraries and for massively multiplexed cloning.}, }
@article {pmid29151903, year = {2017}, author = {Yamamura, K and Baba, Y and Miyake, K and Nakamura, K and Shigaki, H and Mima, K and Kurashige, J and Ishimoto, T and Iwatsuki, M and Sakamoto, Y and Yamashita, Y and Yoshida, N and Watanabe, M and Baba, H}, title = {Fusobacterium nucleatum in gastroenterological cancer: Evaluation of measurement methods using quantitative polymerase chain reaction and a literature review.}, journal = {Oncology letters}, volume = {14}, number = {6}, pages = {6373-6378}, pmid = {29151903}, issn = {1792-1074}, abstract = {The human microbiome Fusobacterium nucleatum, which primarily inhabits the oral cavity, causes periodontal disease and has also been implicated in the development of colorectal cancer. However, whether F. nucleatum is present in other gastroenterological cancer tissues remains to be elucidated. The present study evaluated whether quantitative polymerase chain reaction (qPCR) assays were able to detect F. nucleatum DNA and measure the quantity of F. nucleatum DNA in esophageal, gastric, pancreatic and liver cancer tissues. The accuracy of the qPCR assay was determined from a calibration curve using DNA extracted from cells from the oral cavity. Formalin-fixed paraffin-embedded (FFPE) tumor tissues from 20 patients with gastroenterological [esophageal (squamous cell carcinoma), gastric, colorectal, pancreatic and liver] cancer and 20 matched normal tissues were evaluated for F. nucleatum DNA content. The cycle threshold values in the qPCR assay for F. nucleatum and solute carrier organic anion transporter family member 2A1 (reference sample) decreased linearly with the quantity of input DNA (r[2]>0.99). The F. nucleatum detection rate in esophageal, gastric and colorectal cancer tissues were 20% (4/20), 10% (2/20) and 45% (9/20), respectively. F. nucleatum was not detected in liver and pancreatic cancer tissues. The qPCR results from the frozen and FFPE tissues were consistent. Notably, F. nucleatum was detected at a higher level in superficial areas compared with the invasive areas. F. nucleatum in esophageal, gastric and colorectal cancer tissues was evaluated by qPCR using FFPE tissues. F. nucleatum may be involved in the development of esophageal, gastric and colorectal cancer.}, }
@article {pmid29145477, year = {2017}, author = {Parajuli, A and Grönroos, M and Kauppi, S and Płociniczak, T and Roslund, MI and Galitskaya, P and Laitinen, OH and Hyöty, H and Jumpponen, A and Strömmer, R and Romantschuk, M and Hui, N and Sinkkonen, A}, title = {The abundance of health-associated bacteria is altered in PAH polluted soils-Implications for health in urban areas?.}, journal = {PloS one}, volume = {12}, number = {11}, pages = {e0187852}, pmid = {29145477}, issn = {1932-6203}, mesh = {Bacteria/*isolation &amp; purification ; Finland ; Gas Chromatography-Mass Spectrometry ; Polycyclic Aromatic Hydrocarbons/*analysis ; *Soil Microbiology ; Soil Pollutants/*analysis ; }, abstract = {Long-term exposure to polyaromatic hydrocarbons (PAHs) has been connected to chronic human health disorders. It is also well-known that i) PAH contamination alters soil bacterial communities, ii) human microbiome is associated with environmental microbiome, and iii) alteration in the abundance of members in several bacterial phyla is associated with adverse or beneficial human health effects. We hypothesized that soil pollution by PAHs altered soil bacterial communities that had known associations with human health. The rationale behind our study was to increase understanding and potentially facilitate reconsidering factors that lead to health disorders in areas characterized by PAH contamination. Large containers filled with either spruce forest soil, pine forest soil, peat, or glacial sand were left to incubate or contaminated with creosote. Biological degradation of PAHs was monitored using GC-MS, and the bacterial community composition was analyzed using 454 pyrosequencing. Proteobacteria had higher and Actinobacteria and Bacteroidetes had lower relative abundance in creosote contaminated soils than in non-contaminated soils. Earlier studies have demonstrated that an increase in the abundance of Proteobacteria and decreased abundance of the phyla Actinobacteria and Bacteroidetes are particularly associated with adverse health outcomes and immunological disorders. Therefore, we propose that pollution-induced shifts in natural soil bacterial community, like in PAH-polluted areas, can contribute to the prevalence of chronic diseases. We encourage studies that simultaneously address the classic "adverse toxin effect" paradigm and our novel "altered environmental microbiome" hypothesis.}, }
@article {pmid29141044, year = {2017}, author = {Chen, I and Kelkar, YD and Gu, Y and Zhou, J and Qiu, X and Wu, H}, title = {High-dimensional linear state space models for dynamic microbial interaction networks.}, journal = {PloS one}, volume = {12}, number = {11}, pages = {e0187822}, pmid = {29141044}, issn = {1932-6203}, support = {T32 AI083206/AI/NIAID NIH HHS/United States ; HHSN272201200005C/AI/NIAID NIH HHS/United States ; UL1 TR002001/TR/NCATS NIH HHS/United States ; R01 AI087135/AI/NIAID NIH HHS/United States ; UL1 TR000042/TR/NCATS NIH HHS/United States ; P30 AI078498/AI/NIAID NIH HHS/United States ; }, mesh = {Algorithms ; Female ; Host-Pathogen Interactions ; Humans ; *Microbial Interactions ; *Models, Theoretical ; Vagina/microbiology ; }, abstract = {Medical researchers are increasingly interested in knowing how the complex community of micro-organisms living on human body impacts human health. Key to this is to understand how the microbes interact with each other. Time-course studies on human microbiome indicate that the composition of microbiome changes over short time periods, primarily as a consequence of synergistic and antagonistic interactions of the members of the microbiome with each other and with the environment. Knowledge of the abundance of bacteria-which are the predominant members of the human microbiome-in such time-course studies along with appropriate mathematical models will allow us to identify key dynamic interaction networks within the microbiome. However, the high-dimensional nature of these data poses significant challenges to the development of such mathematical models. We propose a high-dimensional linear State Space Model (SSM) with a new Expectation-Regularization-Maximization (ERM) algorithm to construct a dynamic Microbial Interaction Network (MIN). System noise and measurement noise can be separately specified through SSMs. In order to deal with the problem of high-dimensional parameter space in the SSMs, the proposed new ERM algorithm employs the idea of the adaptive LASSO-based variable selection method so that the sparsity property of MINs can be preserved. We performed simulation studies to evaluate the proposed ERM algorithm for variable selection. The proposed method is applied to identify the dynamic MIN from a time-course vaginal microbiome study of women. This method is amenable to future developments, which may include interactions between microbes and the environment.}, }
@article {pmid29140991, year = {2017}, author = {Schwager, E and Mallick, H and Ventz, S and Huttenhower, C}, title = {A Bayesian method for detecting pairwise associations in compositional data.}, journal = {PLoS computational biology}, volume = {13}, number = {11}, pages = {e1005852}, pmid = {29140991}, issn = {1553-7358}, support = {R01 HG005220/HG/NHGRI NIH HHS/United States ; T32 GM074897/GM/NIGMS NIH HHS/United States ; U54 DE023798/DE/NIDCR NIH HHS/United States ; U54 DK102557/DK/NIDDK NIH HHS/United States ; }, mesh = {Algorithms ; *Bayes Theorem ; Computational Biology/*methods ; *Computer Simulation ; Ecology ; Humans ; Markov Chains ; Microbiota ; *Models, Biological ; Proteobacteria ; }, abstract = {Compositional data consist of vectors of proportions normalized to a constant sum from a basis of unobserved counts. The sum constraint makes inference on correlations between unconstrained features challenging due to the information loss from normalization. However, such correlations are of long-standing interest in fields including ecology. We propose a novel Bayesian framework (BAnOCC: Bayesian Analysis of Compositional Covariance) to estimate a sparse precision matrix through a LASSO prior. The resulting posterior, generated by MCMC sampling, allows uncertainty quantification of any function of the precision matrix, including the correlation matrix. We also use a first-order Taylor expansion to approximate the transformation from the unobserved counts to the composition in order to investigate what characteristics of the unobserved counts can make the correlations more or less difficult to infer. On simulated datasets, we show that BAnOCC infers the true network as well as previous methods while offering the advantage of posterior inference. Larger and more realistic simulated datasets further showed that BAnOCC performs well as measured by type I and type II error rates. Finally, we apply BAnOCC to a microbial ecology dataset from the Human Microbiome Project, which in addition to reproducing established ecological results revealed unique, competition-based roles for Proteobacteria in multiple distinct habitats.}, }
@article {pmid29136663, year = {2017}, author = {Zhang, Y and Alekseyenko, AV}, title = {Phylogenic inference using alignment-free methods for applications in microbial community surveys using 16s rRNA gene.}, journal = {PloS one}, volume = {12}, number = {11}, pages = {e0187940}, pmid = {29136663}, issn = {1932-6203}, support = {R01 CA164964/CA/NCI NIH HHS/United States ; R21 AR067459/AR/NIAMS NIH HHS/United States ; }, mesh = {Microbiota/*genetics ; *Phylogeny ; RNA, Ribosomal, 16S/*genetics ; }, abstract = {The diversity of microbiota is best explored by understanding the phylogenetic structure of the microbial communities. Traditionally, sequence alignment has been used for phylogenetic inference. However, alignment-based approaches come with significant challenges and limitations when massive amounts of data are analyzed. In the recent decade, alignment-free approaches have enabled genome-scale phylogenetic inference. Here we evaluate three alignment-free methods: ACS, CVTree, and Kr for phylogenetic inference with 16s rRNA gene data. We use a taxonomic gold standard to compare the accuracy of alignment-free phylogenetic inference with that of common microbiome-wide phylogenetic inference pipelines based on PyNAST and MUSCLE alignments with FastTree and RAxML. We re-simulate fecal communities from Human Microbiome Project data to evaluate the performance of the methods on datasets with properties of real data. Our comparisons show that alignment-free methods are not inferior to alignment-based methods in giving accurate and robust phylogenic trees. Moreover, consensus ensembles of alignment-free phylogenies are superior to those built from alignment-based methods in their ability to highlight community differences in low power settings. In addition, the overall running times of alignment-based and alignment-free phylogenetic inference are comparable. Taken together our empirical results suggest that alignment-free methods provide a viable approach for microbiome-wide phylogenetic inference.}, }
@article {pmid29134286, year = {2018}, author = {Rossi, C and Marzano, V and Consalvo, A and Zucchelli, M and Levi Mortera, S and Casagrande, V and Mavilio, M and Sacchetta, P and Federici, M and Menghini, R and Urbani, A and Ciavardelli, D}, title = {Proteomic and metabolomic characterization of streptozotocin-induced diabetic nephropathy in TIMP3-deficient mice.}, journal = {Acta diabetologica}, volume = {55}, number = {2}, pages = {121-129}, doi = {10.1007/s00592-017-1074-y}, pmid = {29134286}, issn = {1432-5233}, support = {GR-2011-02346912//Italian Ministry of Health/ ; 2-SRA-2014-262-Q-R//Juvenile Diabetes Research Foundation JDRF/ ; Fondazione Roma 2008//Fondazione Roma/ ; }, mesh = {Animals ; Diabetes Mellitus, Experimental/chemically induced/complications/*metabolism ; Diabetic Nephropathies/chemically induced/genetics/*metabolism/pathology ; Kidney/metabolism ; Kidney Failure, Chronic/chemically induced/genetics/*metabolism/pathology ; Lipid Metabolism ; Metabolome ; *Metabolomics ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Proteome/analysis/metabolism ; *Proteomics ; Streptozocin ; Tissue Inhibitor of Metalloproteinase-3/*genetics ; }, abstract = {AIMS: The tissue inhibitor of metalloproteinase TIMP3 is a stromal protein that restrains the activity of both protease and receptor in the extracellular matrix and has been found to be down-regulated in diabetic nephropathy (DN), the leading cause of end-stage renal disease in developed countries.<br><br>METHODS: In order to gain deeper insights on the association of loss of TIMP3 and DN, we performed differential proteomic analysis of kidney and blood metabolic profiling of wild-type and Timp3-knockout mice before and after streptozotocin (STZ) treatment, widely used to induce insulin deficiency and hyperglycemia.<br><br>RESULTS: Kidney proteomic data and blood metabolic profiles suggest significant alterations of peroxisomal and mitochondrial fatty acids &#x3b2;-oxidation in Timp3-knockout mice compared to wild-type mice under basal condition. These alterations were exacerbated in response to STZ treatment.<br><br>CONCLUSIONS: Proteomic and metabolomic approaches showed that loss of TIMP3 alone or in combination with STZ treatment results in significant alterations of kidney lipid metabolism and peripheral acylcarnitine levels, supporting the idea that loss of TIMP3 may generate a phenotype more prone to DN.}, }
@article {pmid29134235, year = {2018}, author = {Ma, ZS}, title = {Correction to: The P/N (Positive-to-Negative Links) Ratio in Complex Networks-A Promising In Silico Biomarker for Detecting Changes Occurring in the Human Microbiome.}, journal = {Microbial ecology}, volume = {75}, number = {4}, pages = {1074}, doi = {10.1007/s00248-017-1107-7}, pmid = {29134235}, issn = {1432-184X}, abstract = {The original version of this article unfortunately contained a missing image. The flowchart was not captured in PDF version. The original article was corrected.}, }
@article {pmid29129355, year = {2018}, author = {Li, J and Fu, R and Yang, Y and Horz, HP and Guan, Y and Lu, Y and Lou, H and Tian, L and Zheng, S and Liu, H and Shi, M and Tang, K and Wang, S and Xu, S}, title = {A metagenomic approach to dissect the genetic composition of enterotypes in Han Chinese and two Muslim groups.}, journal = {Systematic and applied microbiology}, volume = {41}, number = {1}, pages = {1-12}, doi = {10.1016/j.syapm.2017.09.006}, pmid = {29129355}, issn = {1618-0984}, mesh = {Asian People ; Bacteria/*classification/*genetics ; Cluster Analysis ; DNA, Bacterial/chemistry/genetics ; DNA, Ribosomal/chemistry/genetics ; Ethnicity ; *Gastrointestinal Microbiome ; Genetic Association Studies ; Healthy Volunteers ; Humans ; Islam ; Lysophospholipase/genetics ; *Metagenomics ; *Microbiota ; Phylogeny ; Polymorphism, Single Nucleotide ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; }, abstract = {Distinct enterotypes have been observed in the human gut but little is known about the genetic basis of the microbiome. Moreover, it is not clear how many genetic differences exist between enterotypes within or between populations. In this study, both the 16S rRNA gene and the metagenomes of the gut microbiota were sequenced from 48 Han Chinese, 48 Kazaks, and 96 Uyghurs, and taxonomies were assigned after de novo assembly. Single nucleotide polymorphisms were also identified by referring to data from the Human Microbiome Project. Systematic analysis of the gut communities in terms of their abundance and genetic composition was also performed, together with a genome-wide association study of the host genomes. The gut microbiota of 192 subjects was clearly classified into two enterotypes (Bacteroides and Prevotella). Interestingly, both enterotypes showed a clear genetic differentiation in terms of their functional catalogue of genes, especially for genes involved in amino acid and carbohydrate metabolism. In addition, several differentiated genera and genes were found among the three populations. Notably, one human variant (rs878394) was identified that showed significant association with the abundance of Prevotella, which is linked to LYPLAL1, a gene associated with body fat distribution, the waist-hip ratio and insulin sensitivity. Taken together, considerable differentiation was observed in gut microbes between enterotypes and among populations that was reflected in both the taxonomic composition and the genetic makeup of their functional genes, which could have been influenced by a variety of factors, such as diet and host genetic variation.}, }
@article {pmid29122007, year = {2017}, author = {Li, S and Fuhler, GM and Bn, N and Jose, T and Bruno, MJ and Peppelenbosch, MP and Konstantinov, SR}, title = {Pancreatic cyst fluid harbors a unique microbiome.}, journal = {Microbiome}, volume = {5}, number = {1}, pages = {147}, pmid = {29122007}, issn = {2049-2618}, mesh = {Aged ; Bacteria/classification/genetics/*isolation &amp; purification ; Bacterial Translocation ; Bacteroides/genetics/isolation &amp; purification ; DNA, Bacterial/genetics/*isolation &amp; purification ; Female ; Fusobacterium/genetics/isolation &amp; purification ; Gastrointestinal Tract/microbiology ; High-Throughput Nucleotide Sequencing ; Humans ; Male ; Microbiota/*genetics ; Middle Aged ; Neoplastic Processes ; Pancreas/microbiology/physiopathology ; Pancreatic Cyst/*microbiology ; Phylogeny ; Polymerase Chain Reaction ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; Staphylococcus/genetics/isolation &amp; purification ; }, abstract = {BACKGROUND: It is clear that specific intestinal bacteria are involved in the development of different premalignant conditions along the gastrointestinal tract. An analysis of the microbial constituents in the context of pancreatic cystic lesions has, however, as yet not been performed. This consideration prompted us to explore whether endoscopically obtained pancreatic cyst fluids (PCF) contain bacterial DNA and to determine the genera of bacteria present in such material.<br><br>METHODS: Total DNA was isolated from 69 PCF samples. Bacterial 16S rRNA gene-specific PCR was performed followed by Sanger sequencing and de novo deep sequencing for the V3-V4 variable region of 16S rRNA&#xa0;gene.<br><br>RESULTS: We observed that 98.2% of the samples were positive in conventional PCR, and that 100% of selected PCF samples (n&#xa0;=&#xa0;33) were positive for bacterial microbiota as determined by next generation sequencing (NGS). Comprehensive NGS data analysis of PCF showed the presence of 408 genera of bacteria, of which 17 bacterial genera were uniquely abundant to PCF, when compared to the Human Microbiome Project (HMP) database and 15 bacterial microbiota were uniquely abundant in HMP only. Bacteroides spp., Escherichia/Shigella spp., and Acidaminococcus spp. which were predominant in PCF, while also a substantial Staphylococcus spp. and Fusobacterium spp. component was detected.<br><br>CONCLUSION: These results reveal and characterize an apparently specific bacterial ecosystem in pancreatic cyst fluid samples and may reflect the local microbiota in the pancreas. Some taxa with potential deleterious functions are present in the bacterial abundance profiles, suggesting that the unique microbiome in this specific niche may contribute to neoplastic processes in the pancreas. Further studies are needed to explore the intricate relationship between pathophysiological status in the host pancreas and its microbiota.}, }
@article {pmid29120742, year = {2017}, author = {Maruvada, P and Leone, V and Kaplan, LM and Chang, EB}, title = {The Human Microbiome and Obesity: Moving beyond Associations.}, journal = {Cell host &amp; microbe}, volume = {22}, number = {5}, pages = {589-599}, doi = {10.1016/j.chom.2017.10.005}, pmid = {29120742}, issn = {1934-6069}, support = {P30 DK042086/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Diet ; Dysbiosis/complications ; Energy Intake ; Energy Metabolism/physiology ; Gastrointestinal Microbiome/physiology ; Gastrointestinal Tract/microbiology ; Humans ; Microbiota/*physiology ; Models, Animal ; *Obesity/microbiology ; }, abstract = {Mounting evidence indicates that the gut microbiome responds to diet, antibiotics, and other external stimuli with speed and high precision and in ways that impact a variety of metabolic conditions including obesity and non-alcoholic fatty liver disease. Despite a decade of research establishing a strong association between the gut microbiota and obesity in humans, a causal relationship and the underlying mechanism remain outstanding. Several technological and methodological limitations in obesity and microbiome research have made it difficult to establish causality in this complex relationship. Additionally, limited collaborative interaction between microbiome and obesity researchers has delayed progress. Here, we discuss the current status of microbiome research as it relates to understanding obesity from the perspective of both communities, outline the underlying research challenges, and suggest directions to advance the obesity-microbiome field as a whole, with particular emphasis on the development of microbiome-targeted therapies for obesity prevention and treatment.}, }
@article {pmid29120486, year = {2017}, author = {Miossec, MJ and Valenzuela, SL and Mendez, KN and Castro-Nallar, E}, title = {Computational Methods for Human Microbiome Analysis.}, journal = {Current protocols in microbiology}, volume = {47}, number = {}, pages = {1E.14.1-1E.14.17}, doi = {10.1002/cpmc.41}, pmid = {29120486}, issn = {1934-8533}, mesh = {Computational Biology/*methods ; Humans ; Metagenomics/*methods ; *Microbiota ; }, abstract = {As the field of microbiomics advances, the burden of computational work that scientists need to perform in order to extract biological insight has grown accordingly. Likewise, while human microbiome analyses are increasingly shifting toward a greater integration of various high-throughput data types, a core number of methods form the basis of nearly every study. In this unit, we present step-by-step protocols for five core stages of human microbiome research. The protocols presented in this unit provide a base case for human microbiome analysis, complete with sufficient detail for researchers to tailor certain aspects of the protocols to the specificities of their data. © 2017 by John Wiley &amp; Sons, Inc.}, }
@article {pmid29116650, year = {2018}, author = {Bik, EM and Ugalde, JA and Cousins, J and Goddard, AD and Richman, J and Apte, ZS}, title = {Microbial biotransformations in the human distal gut.}, journal = {British journal of pharmacology}, volume = {175}, number = {24}, pages = {4404-4414}, pmid = {29116650}, issn = {1476-5381}, mesh = {Biotransformation ; *Gastrointestinal Microbiome ; Gastrointestinal Tract/*metabolism/*microbiology ; Humans ; }, abstract = {The human distal gut is home to a rich and dense microbial community with representatives of all three domains of life which are intricately connected with our physiology and health. The combined genomes of these microbes, collectively called the human microbiome, vastly expand the metabolic capacities of our own genome, allowing us to break down and extract energy from dietary compounds that human enzymes cannot digest. In addition, the variable composition of these communities and their biotransformations might explain inter-individual differences in toxicities, tolerances and efficacies for certain drugs. Recent advances in sequencing technologies and bioinformatics have provided exciting new insights into the genomes of our microbial symbionts, their functional capacities and the interactions between these microbes and their human host. This review summarizes the metabolic conversions of dietary components and pharmaceuticals that take place in the human distal gut, as well as their implications for human health. LINKED ARTICLES: This article is part of a themed section on When Pharmacology Meets the Microbiome: New Targets for Therapeutics? To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v175.24/issuetoc.}, }
@article {pmid29112885, year = {2018}, author = {Neville, BA and Forster, SC and Lawley, TD}, title = {Commensal Koch's postulates: establishing causation in human microbiota research.}, journal = {Current opinion in microbiology}, volume = {42}, number = {}, pages = {47-52}, doi = {10.1016/j.mib.2017.10.001}, pmid = {29112885}, issn = {1879-0364}, support = {//Wellcome Trust/United Kingdom ; }, mesh = {Gastrointestinal Microbiome/genetics/physiology ; Humans ; Metagenomics/methods ; *Microbiota ; Research ; *Symbiosis ; }, abstract = {Advances in high-throughput sequencing technologies and the development of sophisticated bioinformatics analysis methods, algorithms, and pipelines to handle the large amounts of data generated have driven the field of human microbiome research forward. This specialist knowledge has been crucial to thoroughly mine the human gut microbiota, particularly in the absence of methods for the routine cultivation of most enteric microorganisms. In recent years, however, significant efforts have been made to address the 'great plate count anomaly' and to overcome the barriers to cultivation of the fastidious and mostly strictly anaerobic bacteria that reside in the human gut. As a result, many new species have been discovered, characterised, genome sequenced, and deposited in culture collections. These continually expanding resources enable experimental investigation of the human gut microbiota, validation of hypotheses made with sequence-based analyses, and phenotypic characterisation of its constituent microbes. Herein we propose a variant of Koch's postulates, aimed at providing a framework to establish causation in microbiome studies, with a particular focus on demonstrating the health-promoting role of the commensal gut microbiota.}, }
@article {pmid29107345, year = {2018}, author = {Luca, F and Kupfer, SS and Knights, D and Khoruts, A and Blekhman, R}, title = {Functional Genomics of Host-Microbiome Interactions in Humans.}, journal = {Trends in genetics : TIG}, volume = {34}, number = {1}, pages = {30-40}, pmid = {29107345}, issn = {0168-9525}, support = {P30 CA022453/CA/NCI NIH HHS/United States ; R01 GM109215/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Gene Expression Regulation ; *Genetic Variation ; Genome-Wide Association Study ; Genomics/methods ; Humans ; Microbiota/*genetics ; Translational Research, Biomedical ; }, abstract = {The human microbiome has been linked to various host phenotypes and has been implicated in many complex human diseases. Recent genome-wide association studies (GWASs) have used microbiome variation as a complex trait and have uncovered human genetic variants that are associated with the microbiome. Here we summarize results from these studies and illustrate potential regulatory mechanisms by which host genetic variation can interact with microbiome composition. We argue that, similar to human GWASs, it is important to use functional genomics techniques to gain a mechanistic understanding of causal host-microbiome interactions and their role in human disease. We highlight experimental, functional, and computational genomics methodologies for the study of the genomic basis of host-microbiome interactions and describe how these approaches can be utilized to explain how human genetic variation can modulate the effects of the microbiome on the host.}, }
@article {pmid29106667, year = {2018}, author = {Oliveira, FS and Brestelli, J and Cade, S and Zheng, J and Iodice, J and Fischer, S and Aurrecoechea, C and Kissinger, JC and Brunk, BP and Stoeckert, CJ and Fernandes, GR and Roos, DS and Beiting, DP}, title = {MicrobiomeDB: a systems biology platform for integrating, mining and analyzing microbiome experiments.}, journal = {Nucleic acids research}, volume = {46}, number = {D1}, pages = {D684-D691}, pmid = {29106667}, issn = {1362-4962}, mesh = {Animals ; Computer Simulation ; Data Mining/*methods ; *Databases, Genetic ; Datasets as Topic ; Environmental Microbiology ; Genetic Variation ; Humans ; Internet ; *Microbiota ; Mobile Applications ; *Systems Biology ; User-Computer Interface ; Workflow ; }, abstract = {MicrobiomeDB (http://microbiomeDB.org) is a data discovery and analysis platform that empowers researchers to fully leverage experimental variables to interrogate microbiome datasets. MicrobiomeDB was developed in collaboration with the Eukaryotic Pathogens Bioinformatics Resource Center (http://EuPathDB.org) and leverages the infrastructure and user interface of EuPathDB, which allows users to construct in silico experiments using an intuitive graphical 'strategy' approach. The current release of the database integrates microbial census data with sample details for nearly 14 000 samples originating from human, animal and environmental sources, including over 9000 samples from healthy human subjects in the Human Microbiome Project (http://portal.ihmpdcc.org/). Query results can be statistically analyzed and graphically visualized via interactive web applications launched directly in the browser, providing insight into microbial community diversity and allowing users to identify taxa associated with any experimental covariate.}, }
@article {pmid29105344, year = {2019}, author = {Gutiérrez-Barranquero, JA and Reen, FJ and Parages, ML and McCarthy, R and Dobson, ADW and O'Gara, F}, title = {Disruption of N-acyl-homoserine lactone-specific signalling and virulence in clinical pathogens by marine sponge bacteria.}, journal = {Microbial biotechnology}, volume = {12}, number = {5}, pages = {1049-1063}, pmid = {29105344}, issn = {1751-7915}, mesh = {Acyl-Butyrolactones/*metabolism ; Animals ; Biological Products/*metabolism ; Paracoccus/*drug effects ; Porifera/*microbiology ; Pseudoalteromonas/*drug effects ; Psychrobacter/isolation &amp; purification/*metabolism ; Quorum Sensing/*drug effects ; Virulence/drug effects ; }, abstract = {In recent years, the marine environment has been the subject of increasing attention from biotechnological and pharmaceutical industries. A combination of unique physicochemical properties and spatial niche-specific substrates, in wide-ranging and extreme habitats, underscores the potential of the marine environment to deliver on functionally novel bioactivities. One such area of ongoing research is the discovery of compounds that interfere with the cell-cell signalling process called quorum sensing (QS). Described as the next generation of antimicrobials, these compounds can target virulence and persistence of clinically relevant pathogens, independent of any growth-limiting effects. Marine sponges are a rich source of microbial diversity, with dynamic populations in a symbiotic relationship. In this study, we have harnessed the QS inhibition (QSI) potential of marine sponge microbiota and through culture-based discovery have uncovered small molecule signal mimics that neutralize virulence phenotypes in clinical pathogens. This study describes for the first time a marine sponge Psychrobacter sp. isolate B98C22 that blocks QS signalling, while also reporting dual QS/QSI activity in the Pseudoalteromonas sp. J10 and ParacoccusJM45. Isolation of novel QSI activities has significant potential for future therapeutic development, of particular relevance in the light of the pending perfect storm of antibiotic resistance meeting antibiotic drug discovery decline.}, }
@article {pmid29104759, year = {2017}, author = {Guthrie, L and Gupta, S and Daily, J and Kelly, L}, title = {Human microbiome signatures of differential colorectal cancer drug metabolism.}, journal = {NPJ biofilms and microbiomes}, volume = {3}, number = {}, pages = {27}, pmid = {29104759}, issn = {2055-5008}, support = {T32 GM007491/GM/NIGMS NIH HHS/United States ; }, abstract = {It is well appreciated that microbial metabolism of drugs can influence treatment efficacy. Microbial β-glucuronidases in the gut can reactivate the excreted, inactive metabolite of irinotecan, a first-line chemotherapeutic for metastatic colorectal cancer. Reactivation causes adverse drug responses, including severe diarrhea. However, a direct connection between irinotecan metabolism and the composition of an individual's gut microbiota has not previously been made. Here, we report quantitative evidence of inter-individual variability in microbiome metabolism of the inactive metabolite of irinotecan to its active form. We identify a high turnover microbiota metabotype with potentially elevated risk for irinotecan-dependent adverse drug responses. We link the high turnover metabotype to unreported microbial β-glucuronidases; inhibiting these enzymes may decrease irinotecan-dependent adverse drug responses in targeted subsets of patients. In total, this study reveals metagenomic mining of the microbiome, combined with metabolomics, as a non-invasive approach to develop biomarkers for colorectal cancer treatment outcomes.}, }
@article {pmid29101674, year = {2017}, author = {Caminer, AC and Haberman, R and Scher, JU}, title = {Human microbiome, infections, and rheumatic disease.}, journal = {Clinical rheumatology}, volume = {36}, number = {12}, pages = {2645-2653}, pmid = {29101674}, issn = {1434-9949}, support = {K23AR064318//National Institute of Arthritis and Musculoskeletal and Skin Diseases/ ; R03AR072182//National Institute of Arthritis and Musculoskeletal and Skin Diseases/ ; }, mesh = {Animals ; Arthritis, Rheumatoid/immunology/*microbiology ; Disease Models, Animal ; Humans ; *Microbiota ; Spondylarthritis/immunology/*microbiology ; }, abstract = {Microbes have coevolved with their human hosts for millions of years and are vital to their normal development and homoeostasis. It is now clear that there is direct and indirect cross talk between the microbiome and host immune responses. However, the exact mechanisms for this microbial influence in disease pathogenesis remain elusive and are now a major research focus.}, }
@article {pmid29099090, year = {2017}, author = {Leccioli, V and Oliveri, M and Romeo, M and Berretta, M and Rossi, P}, title = {A New Proposal for the Pathogenic Mechanism of Non-Coeliac/Non-Allergic Gluten/Wheat Sensitivity: Piecing Together the Puzzle of Recent Scientific Evidence.}, journal = {Nutrients}, volume = {9}, number = {11}, pages = {}, pmid = {29099090}, issn = {2072-6643}, mesh = {Animals ; Bifidobacterium/*growth &amp; development/metabolism ; Butyrates/metabolism ; Celiac Disease/classification/diagnosis/immunology/*microbiology ; *Dysbiosis ; Evidence-Based Medicine ; Firmicutes/*growth &amp; development/metabolism ; *Gastrointestinal Microbiome ; Glutens/*administration &amp; dosage/immunology ; Humans ; Intestinal Absorption ; Intestines/*microbiology ; Permeability ; Prognosis ; Risk Factors ; Triticum/*adverse effects/immunology ; Wheat Hypersensitivity/classification/diagnosis/immunology/*microbiology ; }, abstract = {Non-coeliac/non-allergic gluten/wheat sensitivity (NCG/WS) is a gluten-related disorder, the pathogenesis of which remains unclear. Recently, the involvement of an increased intestinal permeability has been recognized in the onset of this clinical condition. However, mechanisms through which it takes place are still unclear. In this review, we attempt to uncover these mechanisms by providing, for the first time, an integrated vision of recent scientific literature, resulting in a new hypothesis about the pathogenic mechanisms involved in NCG/WS. According to this, the root cause of NCG/WS is a particular dysbiotic profile characterized by decreased butyrate-producing-Firmicutes and/or Bifidobacteria, leading to low levels of intestinal butyrate. Beyond a critical threshold of the latter, a chain reaction of events and vicious circles occurs, involving other protagonists such as microbial lipopolysaccharide (LPS), intestinal alkaline phosphatase (IAP) and wheat α-amylase trypsin inhibitors (ATIs). NCG/WS is likely to be a multi-factor-onset disorder, probably transient and preventable, related to quality and balance of the diet, and not to the presence of gluten in itself. If future studies confirm our proposal, this would have important implications both for the definition of the disease, as well as for the prevention and therapeutic-nutritional management of individuals with NCG/WS.}, }
@article {pmid29098118, year = {2017}, author = {Kodukula, K and Faller, DV and Harpp, DN and Kanara, I and Pernokas, J and Pernokas, M and Powers, WR and Soukos, NS and Steliou, K and Moos, WH}, title = {Gut Microbiota and Salivary Diagnostics: The Mouth Is Salivating to Tell Us Something.}, journal = {BioResearch open access}, volume = {6}, number = {1}, pages = {123-132}, pmid = {29098118}, issn = {2164-7844}, abstract = {The microbiome of the human body represents a symbiosis of microbial networks spanning multiple organ systems. Bacteria predominantly represent the diversity of human microbiota, but not to be forgotten are fungi, viruses, and protists. Mounting evidence points to the fact that the "microbial signature" is host-specific and relatively stable over time. As our understanding of the human microbiome and its relationship to the health of the host increases, it is becoming clear that many and perhaps most chronic conditions have a microbial involvement. The oral and gastrointestinal tract microbiome constitutes the bulk of the overall human microbial load, and thus presents unique opportunities for advancing human health prognosis, diagnosis, and therapy development. This review is an attempt to catalog a broad diversity of recent evidence and focus it toward opportunities for prevention and treatment of debilitating illnesses.}, }
@article {pmid29095820, year = {2017}, author = {Marzano, V and Mancinelli, L and Bracaglia, G and Del Chierico, F and Vernocchi, P and Di Girolamo, F and Garrone, S and Tchidjou Kuekou, H and D'Argenio, P and Dallapiccola, B and Urbani, A and Putignani, L}, title = {"Omic" investigations of protozoa and worms for a deeper understanding of the human gut "parasitome".}, journal = {PLoS neglected tropical diseases}, volume = {11}, number = {11}, pages = {e0005916}, pmid = {29095820}, issn = {1935-2735}, mesh = {Animals ; Entamoeba histolytica/genetics/metabolism ; Gastrointestinal Microbiome ; Gastrointestinal Tract/*parasitology ; *Genomics ; Giardia/genetics/metabolism ; Helminths/genetics/physiology ; *Host-Parasite Interactions ; Humans ; *Metabolomics ; Mice ; Parasites/*physiology ; *Proteomics ; Taenia solium/genetics/metabolism ; }, abstract = {The human gut has been continuously exposed to a broad spectrum of intestinal organisms, including viruses, bacteria, fungi, and parasites (protozoa and worms), over millions of years of coevolution, and plays a central role in human health. The modern lifestyles of Western countries, such as the adoption of highly hygienic habits, the extensive use of antimicrobial drugs, and increasing globalisation, have dramatically altered the composition of the gut milieu, especially in terms of its eukaryotic "citizens." In the past few decades, numerous studies have highlighted the composition and role of human intestinal bacteria in physiological and pathological conditions, while few investigations exist on gut parasites and particularly on their coexistence and interaction with the intestinal microbiota. Studies of the gut "parasitome" through "omic" technologies, such as (meta)genomics, transcriptomics, proteomics, and metabolomics, are herein reviewed to better understand their role in the relationships between intestinal parasites, host, and resident prokaryotes, whether pathogens or commensals. Systems biology-based profiles of the gut "parasitome" under physiological and severe disease conditions can indeed contribute to the control of infectious diseases and offer a new perspective of omics-assisted tropical medicine.}, }
@article {pmid29094223, year = {2017}, author = {Schorpion, A and Kolasinski, SL}, title = {Can Probiotic Supplements Improve Outcomes in Rheumatoid Arthritis?.}, journal = {Current rheumatology reports}, volume = {19}, number = {11}, pages = {73}, pmid = {29094223}, issn = {1534-6307}, mesh = {Arthritis, Rheumatoid/*drug therapy/microbiology ; *Dietary Supplements ; Humans ; Microbiota/*drug effects ; Probiotics/pharmacology/*therapeutic use ; Treatment Outcome ; }, abstract = {PURPOSE OF REVIEW: The purpose of this review is to frame the discussion of the potential use of probiotics for the management of rheumatoid arthritis (RA) in the historical and scientific context linking the human microbiota to the etiology, pathogenesis, and treatment of RA. Given this context, the review then details the clinical trials that have been carried out so far that have tried to address the question.<br><br>RECENT FINDINGS: A variety of laboratory and clinical observations link the flora of the oral cavity and lower gastrointestinal tract with citrullination, as well as immunological alterations that may contribute to the risk of developing RA. Clinical trials to date have been small and mostly short term. Statistically significant change in certain disparate clinical endpoints has been reported, but these endpoints have varied from study to study and have been of limited clinical significance. No consistent, robust impact on patient reported, or laboratory outcome measures has emerged from clinical trials so far. There remain theoretical reasons to further investigate the use of probiotics as adjunctive therapies for autoimmune disease, but changes in trial design may be needed to reveal the benefit of this intervention.}, }
@article {pmid29075243, year = {2017}, author = {Ambrosi, C and Scribano, D and Aleandri, M and Zagaglia, C and Di Francesco, L and Putignani, L and Palamara, AT}, title = {Acinetobacter baumannii Virulence Traits: A Comparative Study of a Novel Sequence Type with Other Italian Endemic International Clones.}, journal = {Frontiers in microbiology}, volume = {8}, number = {}, pages = {1977}, pmid = {29075243}, issn = {1664-302X}, abstract = {Carbapenem-resistant Acinetobacter baumannii (CRAb) have emerged in recent decades as major causes of nosocomial infections. Resistance is mainly due to overexpression of intrinsic and/or acquired carbapenemases, especially oxacillinases (OXA). In Italy, although the sequence type (ST) 2 and the ST78 are the most frequently detected, we recently reported ST632, a single locus variant of ST2. Therefore, this study was aimed at unraveling common bacterial surface virulence factors involved in pathogenesis and antibiotic resistance in representative CRAb of these ST genotypes. Outer membrane protein (OMP) composition together with motility, biofilm formation, in vitro adherence to, invasion of, and survival within pneumocytes were analyzed. Differently from the carbapenem-susceptible reference strain ATCC 17978, either overexpressed OXA-51 or both OXA-23 and OXA-51 co-purified with OMPs in CRAb. This tight association ensures their maximal concentration on the inner surface of the outer membrane to provide the best protection against carbapenems. These findings led us to propose for the first time a common behavior of OXA enzymes in CRAb. Despite the presence of both OmpA and phosphorylcholine-porinD and the ability of all the strains to adhere to cells, invasion, and survival within pneumocytes was shown only by ST2 and ST78 isolates, sharing the highest number of identified OMPs. Conversely, notwithstanding genetic and OMPs similarities with ST2, ST632 was unable to invade and survive within epithelial cells. Overall, our study shows that different STs share a specific OMP composition, also shaped by overexpressed OXA, that is needed for invasiveness and survival of CRAb.}, }
@article {pmid29064808, year = {2017}, author = {Krajewska-Włodarczyk, M}, title = {[The role of the human microbiom in the pathogenesis of rheumatoid arthritis - a literature review].}, journal = {Wiadomosci lekarskie (Warsaw, Poland : 1960)}, volume = {70}, number = {4}, pages = {798-803}, pmid = {29064808}, issn = {0043-5147}, mesh = {Arthritis, Rheumatoid/*microbiology ; Autoimmune Diseases/microbiology ; Dysbiosis/*microbiology ; *Gastrointestinal Microbiome ; Humans ; *Microbiota ; }, abstract = {Rheumatoid arthritis is a chronic, progressive, autoimmune disease with numerous articular, extra-articular and systemic manifestations. The cause of rheumatoid arthritis is multifactorial including genetic and environmental factors. Recent advantages in sequencing techniques have allowed the deep characterization of the human microbiota. Available evidence confirms the existence of an association between dysbiosis and rheumatoid arthritis but it still remains unclear whether alterations in the microbiome are a pathogenic cause or an effect of autoimmune disease. In patients with rheumatoid arthritis the most supported association between disease and microbiota is with the oral dysbiosis usually observed in patients with periodontitis. Given the strong variability and abundance of microbes living in close relation with human host, it becomes a difficult task to define what should be considered the favorable microbiome. There is need for broader studies to establish how the human microbiome contributes to disease susceptibility, and to characterize the role of microbial diversity in the pathogenesis of rheumatoid arthritis, disease manifestation, and progression. The identification of dysbiosis specific for rheumatoid arthritis and the understanding of the dynamic interaction between microbiota and their host may help in establishing an individualized management for each patient with rheumatoid arthritis, and achieve a better efficacy of the therapy.}, }
@article {pmid29062070, year = {2018}, author = {Cookson, WOCM and Cox, MJ and Moffatt, MF}, title = {New opportunities for managing acute and chronic lung infections.}, journal = {Nature reviews. Microbiology}, volume = {16}, number = {2}, pages = {111-120}, pmid = {29062070}, issn = {1740-1534}, support = {G1000758/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Acute Disease ; Anti-Bacterial Agents/*therapeutic use ; Bacterial Infections/*drug therapy/*microbiology ; Chronic Disease ; Drug Resistance, Bacterial ; Global Health ; Humans ; Lung/microbiology ; Lung Diseases/*drug therapy/*microbiology ; Microbiota ; }, abstract = {Lung diseases caused by microbial infections affect hundreds of millions of children and adults throughout the world. In Western populations, the treatment of lung infections is a primary driver of antibiotic resistance. Traditional therapeutic strategies have been based on the premise that the healthy lung is sterile and that infections grow in a pristine environment. As a consequence, rapid advances in our understanding of the composition of the microbiota of the skin and bowel have not yet been matched by studies of the respiratory tree. The recognition that the lungs are as populated with microorganisms as other mucosal surfaces provides the opportunity to reconsider the mechanisms and management of lung infections. Molecular analyses of the lung microbiota are revealing profound adverse responses to widespread antibiotic use, urbanization and globalization. This Opinion article proposes how technologies and concepts flowing from the Human Microbiome Project can transform the diagnosis and treatment of common lung diseases.}, }
@article {pmid29061894, year = {2017}, author = {Aktipis, A and Maley, CC}, title = {Cooperation and cheating as innovation: insights from cellular societies.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {372}, number = {1735}, pages = {}, pmid = {29061894}, issn = {1471-2970}, support = {P01 CA091955/CA/NCI NIH HHS/United States ; R01 CA140657/CA/NCI NIH HHS/United States ; R01 CA185138/CA/NCI NIH HHS/United States ; }, mesh = {*Biological Evolution ; Cooperative Behavior ; *Eukaryota ; Microbial Interactions ; *Microbiota ; Models, Biological ; }, abstract = {The capacity to innovate is often considered a defining feature of human societies, but it is not a capacity that is unique to human societies: innovation occurs in cellular societies as well. Cellular societies such as multicellular bodies and microbial communities, including the human microbiome, are capable of innovation in response to novel opportunities and threats. Multicellularity represents a suite of innovations for cellular cooperation, but multicellularity also opened up novel opportunities for cells to cheat, exploiting the infrastructure and resources of the body. Multicellular bodies evolve less quickly than the cells within them, leaving them vulnerable to cellular innovations that can lead to cancer and infections. In order to counter these threats, multicellular bodies deploy additional innovations including the adaptive immune system and the development of partnerships with preferred microbial partners. What can we learn from examining these innovations in cooperation and cheating in cellular societies? First, innovation in social systems involves a constant tension between novel mechanisms that enable greater size and complexity of cooperative entities and novel ways of cheating. Second, cultivating cooperation with partners who can rapidly and effectively innovate (such as microbes) is important for large entities including multicellular bodies. And third, multicellularity enabled cells to manage risk socially, allowing organisms to survive in challenging environments where life would otherwise be impossible. Throughout, we ask how insights from cellular societies might be translated into new innovations in human health and medicine, promoting and protecting the cellular cooperation that makes us viable multicellular organisms.This article is part of the themed issue 'Process and pattern in innovations from cells to societies'.}, }
@article {pmid29042495, year = {2017}, author = {Maier, TV and Lucio, M and Lee, LH and VerBerkmoes, NC and Brislawn, CJ and Bernhardt, J and Lamendella, R and McDermott, JE and Bergeron, N and Heinzmann, SS and Morton, JT and González, A and Ackermann, G and Knight, R and Riedel, K and Krauss, RM and Schmitt-Kopplin, P and Jansson, JK}, title = {Impact of Dietary Resistant Starch on the Human Gut Microbiome, Metaproteome, and Metabolome.}, journal = {mBio}, volume = {8}, number = {5}, pages = {}, pmid = {29042495}, issn = {2150-7511}, support = {RC1 DK086472/DK/NIDDK NIH HHS/United States ; }, mesh = {Bacteria/classification/drug effects/genetics/growth &amp; development ; DNA, Bacterial/chemistry/genetics ; DNA, Ribosomal/chemistry/genetics ; Diet/methods ; Gastrointestinal Microbiome/*drug effects ; Humans ; Metabolome/*drug effects ; Metabolomics ; Microbiota/*drug effects ; Proteome/*drug effects ; Proteomics ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; Starch/*administration &amp; dosage ; }, abstract = {Diet can influence the composition of the human microbiome, and yet relatively few dietary ingredients have been systematically investigated with respect to their impact on the functional potential of the microbiome. Dietary resistant starch (RS) has been shown to have health benefits, but we lack a mechanistic understanding of the metabolic processes that occur in the gut during digestion of RS. Here, we collected samples during a dietary crossover study with diets containing large or small amounts of RS. We determined the impact of RS on the gut microbiome and metabolic pathways in the gut, using a combination of "omics" approaches, including 16S rRNA gene sequencing, metaproteomics, and metabolomics. This multiomics approach captured changes in the abundance of specific bacterial species, proteins, and metabolites after a diet high in resistant starch (HRS), providing key insights into the influence of dietary interventions on the gut microbiome. The combined data showed that a high-RS diet caused an increase in the ratio of Firmicutes to Bacteroidetes, including increases in relative abundances of some specific members of the Firmicutes and concurrent increases in enzymatic pathways and metabolites involved in lipid metabolism in the gut.IMPORTANCE This work was undertaken to obtain a mechanistic understanding of the complex interplay between diet and the microorganisms residing in the intestine. Although it is known that gut microbes play a key role in digestion of the food that we consume, the specific contributions of different microorganisms are not well understood. In addition, the metabolic pathways and resultant products of metabolism during digestion are highly complex. To address these knowledge gaps, we used a combination of molecular approaches to determine the identities of the microorganisms in the gut during digestion of dietary starch as well as the metabolic pathways that they carry out. Together, these data provide a more complete picture of the function of the gut microbiome in digestion, including links between an RS diet and lipid metabolism and novel linkages between specific gut microbes and their metabolites and proteins produced in the gut.}, }
@article {pmid29040806, year = {2018}, author = {Burch, JM and Mashayekh, S and Wykoff, DD and Grimes, CL}, title = {Bacterial Derived Carbohydrates Bind Cyr1 and Trigger Hyphal Growth in Candida albicans.}, journal = {ACS infectious diseases}, volume = {4}, number = {1}, pages = {53-58}, pmid = {29040806}, issn = {2373-8227}, support = {P20 GM104316/GM/NIGMS NIH HHS/United States ; P30 GM110758/GM/NIGMS NIH HHS/United States ; }, mesh = {Bacteria/*metabolism ; Candida albicans/*physiology ; *Carbohydrate Metabolism ; Carbohydrates ; Hyphae/*growth &amp; development/*metabolism ; Mitochondrial Proteins/*metabolism ; Protein Binding ; }, abstract = {The dimorphic yeast Candida albicans is the most common pathogenic fungus found in humans. While this species is normally commensal, a morphological switch from budding yeast to filamentous hyphae allows the fungi to invade epithelial cells and cause infections. The phenotypic change is controlled by the adenylyl cyclase, Cyr1. Interestingly, this protein contains a leucine-rich repeat (LRR) domain, which is commonly found in innate immune receptors from plants and animals. A functional and pure LRR domain was obtained in high yields from E. coli expression. Utilizing a surface plasmon resonance assay, the LRR was found to bind diverse bacterial derived carbohydrates with high affinity. This domain is capable of binding fragments of peptidoglycan, a carbohydrate polymer component of the bacterial cell wall, as well as anthracyclines produced by Streptomyces, leading to hyphae formation. These findings add another dimension to the human microbiome, taking into account yeast-bacteria interactions that occur in the host.}, }
@article {pmid29040451, year = {2018}, author = {Chen, J and King, E and Deek, R and Wei, Z and Yu, Y and Grill, D and Ballman, K and Stegle, O}, title = {An omnibus test for differential distribution analysis of microbiome sequencing data.}, journal = {Bioinformatics (Oxford, England)}, volume = {34}, number = {4}, pages = {643-651}, doi = {10.1093/bioinformatics/btx650}, pmid = {29040451}, issn = {1367-4811}, mesh = {Arthritis, Rheumatoid/microbiology ; Humans ; Inflammatory Bowel Diseases/microbiology ; Metagenomics/*methods ; Microbiota/*genetics ; *Models, Statistical ; *Software ; }, abstract = {MOTIVATION: One objective of human microbiome studies is to identify differentially abundant microbes across biological conditions. Previous statistical methods focus on detecting the shift in the abundance and/or prevalence of the microbes and treat the dispersion (spread of the data) as a nuisance. These methods also assume that the dispersion is the same across conditions, an assumption which may not hold in presence of sample heterogeneity. Moreover, the widespread outliers in the microbiome sequencing data make existing parametric models not overly robust. Therefore, a robust and powerful method that allows covariate-dependent dispersion and addresses outliers is still needed for differential abundance analysis.<br><br>RESULTS: We introduce a novel test for differential distribution analysis of microbiome sequencing data by jointly testing the abundance, prevalence and dispersion. The test is built on a zero-inflated negative binomial regression model and winsorized count data to account for zero-inflation and outliers. Using simulated data and real microbiome sequencing datasets, we show that our test is robust across various biological conditions and overall more powerful than previous methods.<br><br>R package is available at https://github.com/jchen1981/MicrobiomeDDA.<br><br>CONTACT: chen.jun2@mayo.edu or zhiwei@njit.edu.<br><br>SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.}, }
@article {pmid29039256, year = {2017}, author = {Woodworth, MH and Sitchenko, KL and Carpentieri, C and Friedman-Moraco, RJ and Wang, T and Kraft, CS}, title = {Ethical Considerations in Microbial Therapeutic Clinical Trials.}, journal = {The New bioethics : a multidisciplinary journal of biotechnology and the body}, volume = {23}, number = {3}, pages = {210-218}, pmid = {29039256}, issn = {2050-2885}, support = {UL1 TR000454/TR/NCATS NIH HHS/United States ; UL1 TR002378/TR/NCATS NIH HHS/United States ; }, mesh = {Clinical Trials as Topic/*ethics ; Clostridioides difficile/isolation &amp; purification ; Clostridium Infections/*therapy ; Fecal Microbiota Transplantation/*ethics ; Gastrointestinal Microbiome ; Humans ; }, abstract = {As understanding of the human microbiome improves, novel therapeutic targets to improve human health with microbial therapeutics will continue to expand. We outline key considerations of balancing risks and benefits, optimising access, returning key results to research participants, and potential conflicts of interest.}, }
@article {pmid29038470, year = {2017}, author = {Ma, ZS and Ye, D}, title = {Trios-promising in silico biomarkers for differentiating the effect of disease on the human microbiome network.}, journal = {Scientific reports}, volume = {7}, number = {1}, pages = {13259}, pmid = {29038470}, issn = {2045-2322}, mesh = {Biomarkers/*metabolism ; Humans ; Microbiota/genetics/*physiology ; *Models, Theoretical ; }, abstract = {Recent advances in the HMP (human microbiome project) research have revealed profound implications of the human microbiome to our health and diseases. We postulated that there should be distinctive features associated with healthy and/or diseased microbiome networks. Following Occam's razor principle, we further hypothesized that triangle motifs or trios, arguably the simplest motif in a complex network of the human microbiome, should be sufficient to detect changes that occurred in the diseased microbiome. Here we test our hypothesis with six HMP datasets that cover five major human microbiome sites (gut, lung, oral, skin, and vaginal). The tests confirm our hypothesis and demonstrate that the trios involving the special nodes (e.g., most abundant OTU or MAO, and most dominant OTU or MDO, etc.) and interactions types (positive vs. negative) can be a powerful tool to differentiate between healthy and diseased microbiome samples. Our findings suggest that 12 kinds of trios (especially, dominantly inhibitive trio with mixed strategy, dominantly inhibitive trio with pure strategy, and fully facilitative strategy) may be utilized as in silico biomarkers for detecting disease-associated changes in the human microbiome, and may play an important role in personalized precision diagnosis of the human microbiome associated diseases.}, }
@article {pmid29030459, year = {2017}, author = {Ribado, JV and Ley, C and Haggerty, TD and Tkachenko, E and Bhatt, AS and Parsonnet, J}, title = {Household triclosan and triclocarban effects on the infant and maternal microbiome.}, journal = {EMBO molecular medicine}, volume = {9}, number = {12}, pages = {1732-1741}, pmid = {29030459}, issn = {1757-4684}, support = {K08 CA184420/CA/NCI NIH HHS/United States ; R01 HD063142/HD/NICHD NIH HHS/United States ; R21 ES023371/ES/NIEHS NIH HHS/United States ; T32 HG000044/HG/NHGRI NIH HHS/United States ; }, mesh = {Adult ; Anti-Infective Agents/*pharmacology ; Bacteria/genetics/isolation &amp; purification ; Biodiversity ; Carbanilides/*pharmacology ; Chromatography, High Pressure Liquid ; DNA, Bacterial/chemistry/isolation &amp; purification/metabolism ; Disinfectants/chemistry ; Drug Resistance, Bacterial ; Female ; Gastrointestinal Microbiome/*drug effects ; Humans ; Infant ; Liquid-Liquid Extraction ; Longitudinal Studies ; Proteobacteria/genetics/growth &amp; development ; RNA, Ribosomal, 16S/chemistry/metabolism ; Sequence Analysis, DNA ; Toothpastes/chemistry ; Triclosan/isolation &amp; purification/*pharmacology/urine ; }, abstract = {In 2016, the US Food and Drug Administration banned the use of specific microbicides in some household and personal wash products due to concerns that these chemicals might induce antibiotic resistance or disrupt human microbial communities. Triclosan and triclocarban (referred to as TCs) are the most common antimicrobials in household and personal care products, but the extent to which TC exposure perturbs microbial communities in humans, particularly during infant development, was unknown. We conducted a randomized intervention of TC-containing household and personal care products during the first year following birth to characterize whether TC exposure from wash products perturbs microbial communities in mothers and their infants. Longitudinal survey of the gut microbiota using 16S ribosomal RNA amplicon sequencing showed that TC exposure from wash products did not induce global reconstruction or loss of microbial diversity of either infant or maternal gut microbiotas. Broadly antibiotic-resistant species from the phylum Proteobacteria, however, were enriched in stool samples from mothers in TC households after the introduction of triclosan-containing toothpaste. When compared by urinary triclosan level, agnostic to treatment arm, infants with higher triclosan levels also showed an enrichment of Proteobacteria species. Despite the minimal effects of TC exposure from wash products on the gut microbial community of infants and adults, detected taxonomic differences highlight the need for consumer safety testing of antimicrobial self-care products on the human microbiome and on antibiotic resistance.}, }
@article {pmid29028892, year = {2018}, author = {Weber, N and Liou, D and Dommer, J and MacMenamin, P and Quiñones, M and Misner, I and Oler, AJ and Wan, J and Kim, L and Coakley McCarthy, M and Ezeji, S and Noble, K and Hurt, DE}, title = {Nephele: a cloud platform for simplified, standardized and reproducible microbiome data analysis.}, journal = {Bioinformatics (Oxford, England)}, volume = {34}, number = {8}, pages = {1411-1413}, pmid = {29028892}, issn = {1367-4811}, mesh = {*Cloud Computing ; Computational Biology/*methods ; Humans ; Metagenomics/methods ; Microbiota/*genetics ; Sequence Analysis, DNA/methods ; Sequence Analysis, RNA ; *Software ; }, abstract = {MOTIVATION: Widespread interest in the study of the microbiome has resulted in data proliferation and the development of powerful computational tools. However, many scientific researchers lack the time, training, or infrastructure to work with large datasets or to install and use command line tools.<br><br>RESULTS: The National Institute of Allergy and Infectious Diseases (NIAID) has created Nephele, a cloud-based microbiome data analysis platform with standardized pipelines and a simple web interface for transforming raw data into biological insights. Nephele integrates common microbiome analysis tools as well as valuable reference datasets like the healthy human subjects cohort of the Human Microbiome Project (HMP). Nephele is built on the Amazon Web Services cloud, which provides centralized and automated storage and compute capacity, thereby reducing the burden on researchers and their institutions.<br><br>https://nephele.niaid.nih.gov and https://github.com/niaid/Nephele.<br><br>CONTACT: darrell.hurt@nih.gov.}, }
@article {pmid29028668, year = {2018}, author = {Hager, CL and Ghannoum, MA}, title = {The mycobiome in HIV.}, journal = {Current opinion in HIV and AIDS}, volume = {13}, number = {1}, pages = {69-72}, pmid = {29028668}, issn = {1746-6318}, support = {R01 DE024228/DE/NIDCR NIH HHS/United States ; U01 AI105937/AI/NIAID NIH HHS/United States ; }, mesh = {HIV Infections/*pathology ; Humans ; *Microbiota ; Mouth/*microbiology ; *Mycobiome ; Respiratory System/*microbiology ; }, abstract = {PURPOSE OF REVIEW: There are a limited number of studies investigating the association between the microbiome and HIV. Although the majority of these published investigations have focused on the role of the bacterial community (bacteriome) in this setting, a handful of studies have also characterized the role of the mycobiome in HIV-infected individuals. This review will summarize the most recent reports pertaining to the role of the fungal community in HIV.<br><br>RECENT FINDINGS: Differences in the composition of the oral and respiratory mycobiome in HIV-infected individuals compared with uninfected individuals have been reported.<br><br>SUMMARY: Our review shows that studies investigating the role of the mycobiome in the setting of HIV are severely lacking. With recent advances in our understanding of the composition of the human microbiome, investigations into the role of the bacteria and fungus comprising the overall microbiota and how the two interact to influence each other and the host is crucial.}, }
@article {pmid29022944, year = {2017}, author = {Lloyd-Price, J and Mahurkar, A and Rahnavard, G and Crabtree, J and Orvis, J and Hall, AB and Brady, A and Creasy, HH and McCracken, C and Giglio, MG and McDonald, D and Franzosa, EA and Knight, R and White, O and Huttenhower, C}, title = {Erratum: Strains, functions and dynamics in the expanded Human Microbiome Project.}, journal = {Nature}, volume = {551}, number = {7679}, pages = {256}, pmid = {29022944}, issn = {1476-4687}, abstract = {This corrects the article DOI: 10.1038/nature23889.}, }
@article {pmid29018902, year = {2018}, author = {Ma, ZS}, title = {The P/N (Positive-to-Negative Links) Ratio in Complex Networks-A Promising In Silico Biomarker for Detecting Changes Occurring in the Human Microbiome.}, journal = {Microbial ecology}, volume = {75}, number = {4}, pages = {1063-1073}, pmid = {29018902}, issn = {1432-184X}, mesh = {Biodiversity ; *Biomarkers ; Computer Simulation ; Female ; Gastrointestinal Microbiome ; Humans ; Lung/microbiology ; Microbial Interactions/*physiology ; Microbiota/*physiology ; Mouth/microbiology ; Skin/microbiology ; Vagina/microbiology ; }, abstract = {Relatively little progress in the methodology for differentiating between the healthy and diseased microbiomes, beyond comparing microbial community diversities with traditional species richness or Shannon index, has been made. Network analysis has increasingly been called for the task, but most currently available microbiome datasets only allows for the construction of simple species correlation networks (SCNs). The main results from SCN analysis are a series of network properties such as network degree and modularity, but the metrics for these network properties often produce inconsistent evidence. We propose a simple new network property, the P/N ratio, defined as the ratio of positive links to the number of negative links in the microbial SCN. We postulate that the P/N ratio should reflect the balance between facilitative and inhibitive interactions among microbial species, possibly one of the most important changes occurring in diseased microbiome. We tested our hypothesis with five datasets representing five major human microbiome sites and discovered that the P/N ratio exhibits contrasting differences between healthy and diseased microbiomes and may be harnessed as an in silico biomarker for detecting disease-associated changes in the human microbiome, and may play an important role in personalized diagnosis of the human microbiome-associated diseases.}, }
@article {pmid29018846, year = {2017}, author = {Mousa, WK and Athar, B and Merwin, NJ and Magarvey, NA}, title = {Antibiotics and specialized metabolites from the human microbiota.}, journal = {Natural product reports}, volume = {34}, number = {11}, pages = {1302-1331}, doi = {10.1039/c7np00021a}, pmid = {29018846}, issn = {1460-4752}, mesh = {*Anti-Bacterial Agents/isolation &amp; purification/metabolism/pharmacology ; Humans ; *Microbiota ; Molecular Structure ; }, abstract = {Covering: 2000 to 2017Decades of research on human microbiota have revealed much of their taxonomic diversity and established their direct link to health and disease. However, the breadth of bioactive natural products secreted by our microbial partners remains unknown. Of particular interest are antibiotics produced by our microbiota to ward off invasive pathogens. Members of the human microbiota exclusively produce evolved small molecules with selective antimicrobial activity against human pathogens. Herein, we expand upon the current knowledge concerning antibiotics derived from human microbiota and their distribution across body sites. We analyze, using our in-house chem-bioinformatic tools and natural products database, the encoded antibiotic potential of the human microbiome. This compilation of information may create a foundation for the continued exploration of this intriguing resource of chemical diversity and expose challenges and future perspectives to accelerate the discovery rate of small molecules from the human microbiota.}, }
@article {pmid29018189, year = {2017}, author = {Jie, Z and Xia, H and Zhong, SL and Feng, Q and Li, S and Liang, S and Zhong, H and Liu, Z and Gao, Y and Zhao, H and Zhang, D and Su, Z and Fang, Z and Lan, Z and Li, J and Xiao, L and Li, J and Li, R and Li, X and Li, F and Ren, H and Huang, Y and Peng, Y and Li, G and Wen, B and Dong, B and Chen, JY and Geng, QS and Zhang, ZW and Yang, H and Wang, J and Wang, J and Zhang, X and Madsen, L and Brix, S and Ning, G and Xu, X and Liu, X and Hou, Y and Jia, H and He, K and Kristiansen, K}, title = {The gut microbiome in atherosclerotic cardiovascular disease.}, journal = {Nature communications}, volume = {8}, number = {1}, pages = {845}, pmid = {29018189}, issn = {2041-1723}, mesh = {Atherosclerosis/*microbiology ; Case-Control Studies ; Fermentation ; *Gastrointestinal Microbiome/drug effects ; Genome-Wide Association Study ; Humans ; Inflammation/microbiology ; Liver Cirrhosis/microbiology ; *Metagenome ; Metagenomics ; }, abstract = {The gut microbiota has been linked to cardiovascular diseases. However, the composition and functional capacity of the gut microbiome in relation to cardiovascular diseases have not been systematically examined. Here, we perform a metagenome-wide association study on stools from 218 individuals with atherosclerotic cardiovascular disease (ACVD) and 187 healthy controls. The ACVD gut microbiome deviates from the healthy status by increased abundance of Enterobacteriaceae and Streptococcus spp. and, functionally, in the potential for metabolism or transport of several molecules important for cardiovascular health. Although drug treatment represents a confounding factor, ACVD status, and not current drug use, is the major distinguishing feature in this cohort. We identify common themes by comparison with gut microbiome data associated with other cardiometabolic diseases (obesity and type 2 diabetes), with liver cirrhosis, and rheumatoid arthritis. Our data represent a comprehensive resource for further investigations on the role of the gut microbiome in promoting or preventing ACVD as well as other related diseases.The gut microbiota may play a role in cardiovascular diseases. Here, the authors perform a metagenome-wide association study on stools from individuals with atherosclerotic cardiovascular disease and healthy controls, identifying microbial strains and functions associated with the disease.}, }
@article {pmid29018121, year = {2017}, author = {Hooks, KB and O'Malley, MA}, title = {Dysbiosis and Its Discontents.}, journal = {mBio}, volume = {8}, number = {5}, pages = {}, pmid = {29018121}, issn = {2150-7511}, mesh = {Biodiversity ; *Dysbiosis ; Homeostasis ; Humans ; *Microbiota ; }, abstract = {Dysbiosis is a key term in human microbiome research, especially when microbiome patterns are associated with disease states. Although some questions have been raised about how this term is applied, its use continues undiminished in the literature. We investigate the ways in which microbiome researchers discuss dysbiosis and then assess the impact of different concepts of dysbiosis on microbiome research. After an overview of the term's historical roots, we conduct quantitative and qualitative analyses of a large selection of contemporary dysbiosis statements. We categorize both short definitions and longer conceptual statements about dysbiosis. Further analysis allows us to identify the problematic implications of how dysbiosis is used, particularly with regard to causal hypotheses and normal-abnormal distinctions. We suggest that researchers should reflect carefully on the ways in which they discuss dysbiosis, in order for the field to continue to develop greater predictive scope and explanatory depth.}, }
@article {pmid28992056, year = {2017}, author = {Leggett, RM and Clark, MD}, title = {A world of opportunities with nanopore sequencing.}, journal = {Journal of experimental botany}, volume = {68}, number = {20}, pages = {5419-5429}, doi = {10.1093/jxb/erx289}, pmid = {28992056}, issn = {1460-2431}, support = {BBS/E/T/000PR9817/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Computational Biology/instrumentation/*methods ; Genome, Human/genetics ; Genome, Plant/*genetics ; Humans ; Microbiota/genetics ; *Nanopores ; Plants/*genetics ; Sequence Analysis, DNA/instrumentation/*methods ; }, abstract = {Oxford Nanopore Technologies' MinION sequencer was launched in pre-release form in 2014 and represents an exciting new sequencing paradigm. The device offers multi-kilobase reads and a streamed mode of operation that allows processing of reads as they are generated. Crucially, it is an extremely compact device that is powered from the USB port of a laptop computer, enabling it to be taken out of the lab and facilitating previously impossible in-field sequencing experiments to be undertaken. Many of the initial publications concerning the platform focused on provision of tools to access and analyse the new sequence formats and then demonstrating the assembly of microbial genomes. More recently, as throughput and accuracy have increased, it has been possible to begin work involving more complex genomes and metagenomes. With the release of the high-throughput GridION X5 and PromethION platforms, the sequencing of large genomes will become more cost efficient, and enable the leveraging of extremely long (>100 kb) reads for resolution of complex genomic structures. This review provides a brief overview of nanopore sequencing technology, describes the growing range of nanopore bioinformatics tools, and highlights some of the most influential publications that have emerged over the last 2 years. Finally, we look to the future and the potential the platform has to disrupt work in human, microbiome, and plant genomics.}, }
@article {pmid28988258, year = {2017}, author = {Wagner Mackenzie, B and Waite, DW and Hoggard, M and Taylor, MW and Biswas, K and Douglas, RG}, title = {Moving beyond descriptions of diversity: clinical and research implications of bacterial imbalance in chronic rhinosinusitis.}, journal = {Rhinology}, volume = {55}, number = {4}, pages = {291-297}, doi = {10.4193/Rhin17.135}, pmid = {28988258}, issn = {0300-0729}, mesh = {Bacterial Physiological Phenomena ; Chronic Disease ; Discriminant Analysis ; Ecosystem ; Humans ; Machine Learning ; *Microbiota ; Paranasal Sinuses/*microbiology ; Rhinitis/*microbiology/therapy ; Sinusitis/*microbiology/therapy ; }, abstract = {Chronic rhinosinusitis (CRS) is a debilitating disease which affects 5-16% of the general population and involves long-term inflammation of the sinonasal cavity. While microbial involvement in the pathogenesis of CRS has long been suspected, the exact role of microbes remains unclear. Recent application of cultivation-independent, molecular methods has provided much new information, taking advantage of developments in both laboratory- and bioinformatics-based analyses. The aim of this mini-review is to present a variety of available bioinformatics approaches, such as data classification techniques and network analyses, with proven applications in other aspects of human microbiome health and disease research. The uses of molecular techniques in the clinical setting are still in its infancy, but these tools can further our understanding of microbial imbalance during chronic disease and help guide effective patient treatment. The mini-review emphasises ways in which CRS bacterial gene-targeted sequencing data can progress beyond descriptive summaries and toward unlocking the mechanisms by which bacterial communities can be markers for sinus health.}, }
@article {pmid28987073, year = {2017}, author = {Ejtahed, HS and Hasani-Ranjbar, S and Larijani, B}, title = {Human Microbiome as an Approach to Personalized Medicine.}, journal = {Alternative therapies in health and medicine}, volume = {23}, number = {6}, pages = {8-9}, pmid = {28987073}, issn = {1078-6791}, mesh = {Biodiversity ; Humans ; Microbiology/trends ; *Microbiota ; Pharmacogenetics/*trends ; Precision Medicine/*trends ; }, abstract = {Personalized medicine is an approach for medical decisions, practices, and interventions that considers individual variations in genes, environment, and lifestyle for each person. Regarding complex metabolic patterns associated with different diseases, characterizing unique metabolic patterns of each patient seems like a practical approach. We can imagine a future in which routinely analyzing the microbiome allows us to predict individualized responses to different foods and drugs. Microbiome analysis of individuals may be added to future routine personalized medicine protocols after comparing the costs and benefits of microbiome-sequencing technology. Moreover, improved understanding of the human microbiome could lead to the development of novel therapeutic strategies for different diseases. Potential therapeutic agents, such as personalized probiotic and prebiotic supplements, dietary interventions, and fecal microbiota transplantation that can be used to reshape the gut microbiome, represent a reasonable strategy in an era of personalized medicine.}, }
@article {pmid28986319, year = {2017}, author = {Broeckx, G and Vandenheuvel, D and Henkens, T and Kiekens, S and van den Broek, MFL and Lebeer, S and Kiekens, F}, title = {Enhancing the viability of Lactobacillus rhamnosus GG after spray drying and during storage.}, journal = {International journal of pharmaceutics}, volume = {534}, number = {1-2}, pages = {35-41}, doi = {10.1016/j.ijpharm.2017.09.075}, pmid = {28986319}, issn = {1873-3476}, mesh = {Colony Count, Microbial/methods ; Desiccation/methods ; Drug Storage/methods ; Excipients/chemistry ; Freeze Drying/methods ; Hot Temperature ; Humans ; Lacticaseibacillus rhamnosus/*chemistry ; Lactose/chemistry ; Microbial Viability/*drug effects ; Microbiota/physiology ; Powders/chemistry ; Probiotics/chemistry ; Protective Agents/chemistry ; Survival Rate ; Transition Temperature ; Trehalose/chemistry ; }, abstract = {Increasing knowledge about the human microbiome has led to a growing awareness of the potential of applying probiotics to improve our health. The pharmaceutical industry shows an emerging interest in pharmaceutical formulations containing these beneficial microbes, the so-called pharmabiotics. An important manufacturing step is the drying of the probiotics, as this can increase the stability and shelf life of the finished pharmabiotic product. Unfortunately, drying also puts stress on microbial cells, thus causing a decrease in viability. We aimed to examine the effect of different drying media and protective excipients on the viability of the prototype probiotic strain Lactobacillus rhamnosus GG after spray drying and during subsequent storage for 28 weeks. The presence of phosphates in the drying medium showed to have a superior protective effect, especially during long-term storage at room temperature. Addition of lactose or trehalose resulted in significantly improved survival rates after drying as well as during long-term storage for the tested excipients. Both disaccharides are characterized by a high glass transition temperature. Maltodextrin showed less protective capacities compared to lactose and trehalose in all tested conditions. The usage of mannitol or dextran resulted in sticky powders and low yields, so further testing was not possible. In addition to optimizing the viability, future research will also explore the functionality of cellular probiotic components after spray drying in order to safeguard the probiotic activity of the formulated pharmabiotics.}, }
@article {pmid28980268, year = {2017}, author = {Zhu, X and Wang, J and Reyes-Gibby, C and Shete, S}, title = {Processing and Analyzing Human Microbiome Data.}, journal = {Methods in molecular biology (Clifton, N.J.)}, volume = {1666}, number = {}, pages = {649-677}, doi = {10.1007/978-1-4939-7274-6_31}, pmid = {28980268}, issn = {1940-6029}, mesh = {Adenocarcinoma/microbiology ; Bacteria/genetics ; Esophageal Neoplasms/microbiology ; High-Throughput Nucleotide Sequencing/*methods ; Humans ; *Microbiota ; Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, RNA/methods ; *Software ; }, abstract = {The human microbiome is associated with complex disorders such as diabetes, cancer, obesity and cardiovascular disorders. Recent technological developments have allowed researchers to fully quantify the composition of the microbiome using culture-independent approaches, resulting in a large amount of microbiome data, which provide invaluable opportunities to assess the important contributions of the microbiome to human health and disease. In this chapter, we discuss and evaluate multiple statistical approaches for processing, summarizing, and analyzing microbiome data. Specifically, we provide programming scripts for processing microbiome data using QIIME and calculating alpha and beta diversities, assessing the association between diversities and outcomes of interest using R programs, as well as interpretation of results. We illustrate the methods in the context of analyzing the foregut microbiome in esophageal adenocarcinoma.}, }
@article {pmid28971865, year = {2017}, author = {Healey, KR and Nagasaki, Y and Zimmerman, M and Kordalewska, M and Park, S and Zhao, Y and Perlin, DS}, title = {The Gastrointestinal Tract Is a Major Source of Echinocandin Drug Resistance in a Murine Model of Candida glabrata Colonization and Systemic Dissemination.}, journal = {Antimicrobial agents and chemotherapy}, volume = {61}, number = {12}, pages = {}, pmid = {28971865}, issn = {1098-6596}, support = {R01 AI109025/AI/NIAID NIH HHS/United States ; }, mesh = {Aminoglycosides/pharmacology ; Animals ; Antifungal Agents/pharmacokinetics/*pharmacology ; Candida glabrata/*drug effects/genetics/growth &amp; development ; Candidiasis/*drug therapy/immunology/microbiology ; Caspofungin ; Chitin Synthase/antagonists &amp; inhibitors/genetics/metabolism ; Dexamethasone/adverse effects ; Disease Models, Animal ; Drug Administration Schedule ; Drug Resistance, Fungal/genetics ; Drug Tolerance/genetics ; Echinocandins/pharmacokinetics/*pharmacology ; Female ; Fungal Proteins/*genetics/metabolism ; Gastrointestinal Tract/*drug effects/immunology/microbiology ; Glucosyltransferases/*genetics/metabolism ; Humans ; Immunosuppressive Agents/adverse effects ; Isoenzymes/genetics/metabolism ; Lipopeptides/pharmacokinetics/*pharmacology ; Mice ; Microbial Sensitivity Tests ; Mutation ; }, abstract = {Candida species are a part of the human microbiome and can cause systemic infection upon immune suppression. Candida glabrata infections are increasing and have greater rates of antifungal resistance than other species. Here, we present a C. glabrata gastrointestinal (GI) colonization model to explore whether colonized yeast exposed to caspofungin, an echinocandin antifungal, develop characteristic resistance mutations and, upon immunosuppression, breakthrough causing systemic infection. Daily therapeutic dosing (5 mg/kg of body weight) of caspofungin resulted in no reduction in fecal burdens, organ breakthrough rates similar to control groups, and resistance rates (0 to 10%) similar to those reported clinically. Treatment with 20 mg/kg caspofungin initially reduced burdens, but a rebound following 5 to 9 days of treatment was accompanied by high levels of resistance (FKS1/FKS2 mutants). Although breakthrough rates decreased in this group, the same FKS mutants were recovered from organs. In an attempt to negate drug tolerance that is critical for resistance development, we cotreated mice with daily caspofungin and the chitin synthase inhibitor nikkomycin Z. The largest reduction (3 log) in GI burdens was obtained within 3 to 5 days of 20 mg/kg caspofungin plus nikkomycin treatment. Yet, echinocandin resistance, characterized by a novel Fks1-L630R substitution, was identified following 5 to 7 days of treatment. Therapeutic caspofungin plus nikkomycin treatment left GI burdens unchanged but significantly reduced organ breakthrough rates (20%; P < 0.05). Single-dose pharmacokinetics demonstrated low levels of drug penetration into the GI lumen posttreatment with caspofungin. Overall, we show that C. glabrata echinocandin resistance can arise within the GI tract and that resistant mutants can readily disseminate upon immunosuppression.}, }
@article {pmid28968799, year = {2018}, author = {Äijö, T and Müller, CL and Bonneau, R}, title = {Temporal probabilistic modeling of bacterial compositions derived from 16S rRNA sequencing.}, journal = {Bioinformatics (Oxford, England)}, volume = {34}, number = {3}, pages = {372-380}, pmid = {28968799}, issn = {1367-4811}, mesh = {Bacteria/genetics/*isolation &amp; purification ; Gastrointestinal Microbiome/*genetics ; *Genome, Bacterial ; High-Throughput Nucleotide Sequencing/methods ; Humans ; Metagenomics/*methods ; *Models, Statistical ; RNA, Ribosomal, 16S/*analysis ; Sequence Analysis, DNA/methods ; }, abstract = {MOTIVATION: The number of microbial and metagenomic studies has increased drastically due to advancements in next-generation sequencing-based measurement techniques. Statistical analysis and the validity of conclusions drawn from (time series) 16S rRNA and other metagenomic sequencing data is hampered by the presence of significant amount of noise and missing data (sampling zeros). Accounting uncertainty in microbiome data is often challenging due to the difficulty of obtaining biological replicates. Additionally, the compositional nature of current amplicon and metagenomic data differs from many other biological data types adding another challenge to the data analysis.<br><br>RESULTS: To address these challenges in human microbiome research, we introduce a novel probabilistic approach to explicitly model overdispersion and sampling zeros by considering the temporal correlation between nearby time points using Gaussian Processes. The proposed Temporal Gaussian Process Model for Compositional Data Analysis (TGP-CODA) shows superior modeling performance compared to commonly used Dirichlet-multinomial, multinomial and non-parametric regression models on real and synthetic data. We demonstrate that the nonreplicative nature of human gut microbiota studies can be partially overcome by our method with proper experimental design of dense temporal sampling. We also show that different modeling approaches have a strong impact on ecological interpretation of the data, such as stationarity, persistence and environmental noise models.<br><br>A Stan implementation of the proposed method is available under MIT license at https://github.com/tare/GPMicrobiome.<br><br>CONTACT: taijo@flatironinstitute.org or rb113@nyu.edu.<br><br>SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.}, }
@article {pmid28968702, year = {2019}, author = {Hawinkel, S and Mattiello, F and Bijnens, L and Thas, O}, title = {A broken promise: microbiome differential abundance methods do not control the false discovery rate.}, journal = {Briefings in bioinformatics}, volume = {20}, number = {1}, pages = {210-221}, doi = {10.1093/bib/bbx104}, pmid = {28968702}, issn = {1477-4054}, mesh = {Algorithms ; Biodiversity ; Computational Biology/methods ; Computer Simulation ; Databases, Genetic/statistics &amp; numerical data ; High-Throughput Nucleotide Sequencing/statistics &amp; numerical data ; Humans ; *Microbiota/genetics ; Statistics, Nonparametric ; }, abstract = {High-throughput sequencing technologies allow easy characterization of the human microbiome, but the statistical methods to analyze microbiome data are still in their infancy. Differential abundance methods aim at detecting associations between the abundances of bacterial species and subject grouping factors. The results of such methods are important to identify the microbiome as a prognostic or diagnostic biomarker or to demonstrate efficacy of prodrug or antibiotic drugs. Because of a lack of benchmarking studies in the microbiome field, no consensus exists on the performance of the statistical methods. We have compared a large number of popular methods through extensive parametric and nonparametric simulation as well as real data shuffling algorithms. The results are consistent over the different approaches and all point to an alarming excess of false discoveries. This raises great doubts about the reliability of discoveries in past studies and imperils reproducibility of microbiome experiments. To further improve method benchmarking, we introduce a new simulation tool that allows to generate correlated count data following any univariate count distribution; the correlation structure may be inferred from real data. Most simulation studies discard the correlation between species, but our results indicate that this correlation can negatively affect the performance of statistical methods.}, }
@article {pmid28968189, year = {2018}, author = {Vázquez-Baeza, Y and Callewaert, C and Debelius, J and Hyde, E and Marotz, C and Morton, JT and Swafford, A and Vrbanac, A and Dorrestein, PC and Knight, R}, title = {Impacts of the Human Gut Microbiome on Therapeutics.}, journal = {Annual review of pharmacology and toxicology}, volume = {58}, number = {}, pages = {253-270}, doi = {10.1146/annurev-pharmtox-042017-031849}, pmid = {28968189}, issn = {1545-4304}, mesh = {Animals ; Anti-Inflammatory Agents, Non-Steroidal/pharmacology/therapeutic use ; Antineoplastic Agents/pharmacology/therapeutic use ; Cardiac Glycosides/pharmacology/therapeutic use ; Gastrointestinal Microbiome/*drug effects/*physiology ; Humans ; Microbiota/*drug effects/*physiology ; Signal Transduction/drug effects ; }, abstract = {The human microbiome contains a vast source of genetic and biochemical variation, and its impacts on therapeutic responses are just beginning to be understood. This expanded understanding is especially important because the human microbiome differs far more among different people than does the human genome, and it is also dramatically easier to change. Here, we describe some of the major factors driving differences in the human microbiome among individuals and populations. We then describe some of the many ways in which gut microbes modify the action of specific chemotherapeutic agents, including nonsteroidal anti-inflammatory drugs and cardiac glycosides, and outline the potential of fecal microbiota transplant as a therapeutic. Intriguingly, microbes also alter how hosts respond to therapeutic agents through various pathways acting at distal sites. Finally, we discuss some of the computational and practical issues surrounding use of the microbiome to stratify individuals for drug response, and we envision a future where the microbiome will be modified to increase everyone's potential to benefit from therapy.}, }
@article {pmid28967885, year = {2017}, author = {Sinha, R and Abu-Ali, G and Vogtmann, E and Fodor, AA and Ren, B and Amir, A and Schwager, E and Crabtree, J and Ma, S and ,  and Abnet, CC and Knight, R and White, O and Huttenhower, C}, title = {Assessment of variation in microbial community amplicon sequencing by the Microbiome Quality Control (MBQC) project consortium.}, journal = {Nature biotechnology}, volume = {35}, number = {11}, pages = {1077-1086}, pmid = {28967885}, issn = {1546-1696}, support = {P30 DK043351/DK/NIDDK NIH HHS/United States ; U01 HG006537/HG/NHGRI NIH HHS/United States ; U01 HG004866/HG/NHGRI NIH HHS/United States ; U54 DE023798/DE/NIDCR NIH HHS/United States ; R01 HG005220/HG/NHGRI NIH HHS/United States ; R01 HG004872/HG/NHGRI NIH HHS/United States ; R01 HG005969/HG/NHGRI NIH HHS/United States ; R01 CA179243/CA/NCI NIH HHS/United States ; }, mesh = {Bacteria/*genetics ; DNA, Bacterial/*chemistry/*genetics ; Gastrointestinal Microbiome/*genetics ; Humans ; *Microbiota ; Nucleic Acid Amplification Techniques/*methods/*standards ; Reference Standards ; Research Design ; }, abstract = {In order for human microbiome studies to translate into actionable outcomes for health, meta-analysis of reproducible data from population-scale cohorts is needed. Achieving sufficient reproducibility in microbiome research has proven challenging. We report a baseline investigation of variability in taxonomic profiling for the Microbiome Quality Control (MBQC) project baseline study (MBQC-base). Blinded specimen sets from human stool, chemostats, and artificial microbial communities were sequenced by 15 laboratories and analyzed using nine bioinformatics protocols. Variability depended most on biospecimen type and origin, followed by DNA extraction, sample handling environment, and bioinformatics. Analysis of artificial community specimens revealed differences in extraction efficiency and bioinformatic classification. These results may guide researchers in experimental design choices for gut microbiome studies.}, }
@article {pmid28963010, year = {2017}, author = {Coutinho, CMLM and Coutinho-Silva, R and Zinkevich, V and Pearce, CB and Ojcius, DM and Beech, I}, title = {Sulphate-reducing bacteria from ulcerative colitis patients induce apoptosis of gastrointestinal epithelial cells.}, journal = {Microbial pathogenesis}, volume = {112}, number = {}, pages = {126-134}, doi = {10.1016/j.micpath.2017.09.054}, pmid = {28963010}, issn = {1096-1208}, mesh = {Apoptosis/*drug effects ; Bacteria/*drug effects ; Biopsy ; Cell Line ; Coculture Techniques ; Colitis, Ulcerative/*microbiology ; Colon/pathology ; Colonoscopy ; Desulfovibrio/metabolism ; Epithelial Cells/*metabolism/pathology ; Escherichia coli/isolation &amp; purification/metabolism ; Feces/microbiology ; Gastrointestinal Tract/*metabolism ; Humans ; Inflammatory Bowel Diseases/microbiology ; Intestinal Mucosa/microbiology/pathology ; Sulfates/*pharmacology ; United Kingdom ; }, abstract = {The human microbiome consists of a multitude of bacterial genera and species which continuously interact with one another and their host establishing a metabolic equilibrium. The dysbiosis can lead to the development of pathology, such as inflammatory bowel diseases. Sulfide-producing prokaryotes, including sulphate-reducing bacteria (SRB) constituting different genera, including the Desulfovibrio, are commonly detected within the human microbiome recovered from fecal material or colonic biopsy samples. It has been proposed that SRB likely contribute to colonic pathology, for example ulcerative colitis (UC). The interaction of SRB with the human colon and intestinal epithelial cell lines has been investigated using Desulfovibrio indonesiensis as a model mono-culture and in a co-culture with E. coli isolate, and with SRB consortia from human biopsy samples. We find that D. indonesiensis, whether as a mono- or co-culture, was internalized and induced apoptosis in colon epithelial cells. This effect was enhanced in the presence of E. coli. The SRB combination obtained through enrichment of biopsies from UC patients induced apoptosis of a human intestinal epithelial cell line. This response was not observed in SRB enrichments from healthy (non-UC) controls. Importantly, apoptosis was detected in epithelial cells from UC patients and was not seen in epithelial cells of healthy donors. Furthermore, the antibody raised against exopolysaccharides (EPS) of D. indonesiensis cross reacted with the SRB population from UC patients but not with the SRB combination from non-UC controls. This study reinforces a correlation between the presence of sulphate-reducing bacteria and an inflammatory response in UC sufferers.}, }
@article {pmid28961122, year = {2020}, author = {Ma, Y and Hu, X and He, T and Jiang, X}, title = {Clustering and Integrating of Heterogeneous Microbiome Data by Joint Symmetric Nonnegative Matrix Factorization with Laplacian Regularization.}, journal = {IEEE/ACM transactions on computational biology and bioinformatics}, volume = {17}, number = {3}, pages = {788-795}, doi = {10.1109/TCBB.2017.2756628}, pmid = {28961122}, issn = {1557-9964}, mesh = {*Cluster Analysis ; Computational Biology/*methods ; Databases, Genetic ; Humans ; Microbiota/*genetics ; Phylogeny ; Statistics as Topic ; }, abstract = {Many datasets that exists in the real world are often comprised of different representations or views which provide complementary information to each other. To integrate information from multiple views, data integration approaches such as nonnegative matrix factorization (NMF) have been developed to combine multiple heterogeneous data simultaneously to obtain a comprehensive representation. In this paper, we proposed a novel variant of symmetric nonnegative matrix factorization (SNMF), called Laplacian regularization based joint symmetric nonnegative matrix factorization (LJ-SNMF) for clustering multi-view data. We conduct extensive experiments on several realistic datasets including Human Microbiome Project data. The experimental results show that the proposed method outperforms other variants of NMF, which suggests the potential application of LJ-SNMF in clustering multi-view datasets. Additionally, we also demonstrate the capability of LJ-SNMF in community finding.}, }
@article {pmid28959368, year = {2017}, author = {Chen, EZ and Bushman, FD and Li, H}, title = {A Model-Based Approach For Species Abundance Quantification Based On Shotgun Metagenomic Data.}, journal = {Statistics in biosciences}, volume = {9}, number = {1}, pages = {13-27}, pmid = {28959368}, issn = {1867-1764}, support = {R01 CA127334/CA/NCI NIH HHS/United States ; R01 GM097505/GM/NIGMS NIH HHS/United States ; }, abstract = {The human microbiome, which includes the collective microbes residing in or on the human body, has a profound influence on the human health. DNA sequencing technology has made the large-scale human microbiome studies possible by using shotgun metagenomic sequencing. One important aspect of data analysis of such metagenomic data is to quantify the bacterial abundances based on the metagenomic sequencing data. Existing methods almost always quantify such abundances one sample at a time, which ignore certain systematic differences in read coverage along the genomes due to GC contents, copy number variation and the bacterial origin of replication. In order to account for such differences in read counts, we propose a multi-sample Poisson model to quantify microbial abundances based on read counts that are assigned to species-specific taxonomic markers. Our model takes into account the marker-specific effects when normalizing the sequencing count data in order to obtain more accurate quantification of the species abundances. Compared to currently available methods on simulated data and real data sets, our method has demonstrated an improved accuracy in bacterial abundance quantification, which leads to more biologically interesting results from downstream data analysis.}, }
@article {pmid28954525, year = {2018}, author = {Chung, SY and Ravel, J and Regan, M}, title = {Clinical Relevance of Gastrointestinal Microbiota During Pregnancy: A Primer for Nurses.}, journal = {Biological research for nursing}, volume = {20}, number = {1}, pages = {84-102}, pmid = {28954525}, issn = {1552-4175}, support = {R01 NR014826/NR/NINR NIH HHS/United States ; }, mesh = {Adult ; Female ; Gastrointestinal Microbiome/*physiology ; Gastrointestinal Tract/*microbiology ; Humans ; Infant, Newborn ; Pregnancy ; Pregnancy Outcome ; }, abstract = {Emerging evidence about the human microbiome, a collective term for all the microorganisms living in and on the human body, consistently demonstrates the critical influence it has on host physiology and disease risk. The microbiota in the gastrointestinal (GI) tract has the most significant and far-reaching effect on human physiology. The maternal GI microbiota can decrease the risk of adverse pregnancy outcomes by modulating energy extraction, glucose metabolism, vitamin production, and host immunity essential for optimal maternal and neonatal health. Moreover, the maternal GI microbiota is thought to influence colonization of the fetus and neonate that may predispose them to different health trajectories. This article provides a basic understanding about the influence of the structure of the maternal GI microbiota, the fundamental role it plays during pregnancy, and the factors that influence the structure, and subsequently function, of the GI microbiota in the general and pregnant population. While only a small number of studies have examined this topic during pregnancy, the preponderance of the evidence supports the need to clarify baseline structure and function of GI microbiota and its associations with pregnancy outcomes. In addition, the results from the studies conducted in the general population can be extrapolated to pregnancy in many cases. This knowledge is essential for clinicians who need to understand the implications of the microbiota for disease and wellness in order to address the care factors that may adversely influence the GI microbiota during pregnancy.}, }
@article {pmid28953883, year = {2017}, author = {Lloyd-Price, J and Mahurkar, A and Rahnavard, G and Crabtree, J and Orvis, J and Hall, AB and Brady, A and Creasy, HH and McCracken, C and Giglio, MG and McDonald, D and Franzosa, EA and Knight, R and White, O and Huttenhower, C}, title = {Strains, functions and dynamics in the expanded Human Microbiome Project.}, journal = {Nature}, volume = {550}, number = {7674}, pages = {61-66}, pmid = {28953883}, issn = {1476-4687}, support = {U54 HG004973/HG/NHGRI NIH HHS/United States ; U54 DK102557/DK/NIDDK NIH HHS/United States ; P30 DK043351/DK/NIDDK NIH HHS/United States ; U01 HG006537/HG/NHGRI NIH HHS/United States ; U54 AI084844/AI/NIAID NIH HHS/United States ; U01 HG004866/HG/NHGRI NIH HHS/United States ; U54 HG004968/HG/NHGRI NIH HHS/United States ; R01 HG004872/HG/NHGRI NIH HHS/United States ; U54 HG003079/HG/NHGRI NIH HHS/United States ; U54 HG004969/HG/NHGRI NIH HHS/United States ; }, mesh = {Datasets as Topic ; Humans ; Metagenome/genetics/physiology ; Microbiota/genetics/*physiology ; Molecular Sequence Annotation ; National Institutes of Health (U.S.) ; Organ Specificity ; *Phylogeny ; Spatio-Temporal Analysis ; Time Factors ; United States ; }, abstract = {The characterization of baseline microbial and functional diversity in the human microbiome has enabled studies of microbiome-related disease, diversity, biogeography, and molecular function. The National Institutes of Health Human Microbiome Project has provided one of the broadest such characterizations so far. Here we introduce a second wave of data from the study, comprising 1,631 new metagenomes (2,355 total) targeting diverse body sites with multiple time points in 265 individuals. We applied updated profiling and assembly methods to provide new characterizations of microbiome personalization. Strain identification revealed subspecies clades specific to body sites; it also quantified species with phylogenetic diversity under-represented in isolate genomes. Body-wide functional profiling classified pathways into universal, human-enriched, and body site-enriched subsets. Finally, temporal analysis decomposed microbial variation into rapidly variable, moderately variable, and stable subsets. This study furthers our knowledge of baseline human microbial diversity and enables an understanding of personalized microbiome function and dynamics.}, }
@article {pmid28952002, year = {2019}, author = {Leng, J and Peruluswami, P and Bari, S and Gaur, S and Radparvar, F and Parvez, F and Chen, Y and Flores, C and Gany, F}, title = {South Asian Health: Inflammation, Infection, Exposure, and the Human Microbiome.}, journal = {Journal of immigrant and minority health}, volume = {21}, number = {Suppl 1}, pages = {26-36}, pmid = {28952002}, issn = {1557-1920}, support = {U54 CA137788/CA/NCI NIH HHS/United States ; R13 MD007147-01A1/MD/NIMHD NIH HHS/United States ; R21 NR019188/NR/NINR NIH HHS/United States ; R13 MD007147/MD/NIMHD NIH HHS/United States ; K24 HL150476/HL/NHLBI NIH HHS/United States ; P30CA008748/CA/NCI NIH HHS/United States ; P30 CA008748/CA/NCI NIH HHS/United States ; U54 CA132378/CA/NCI NIH HHS/United States ; R01 NR015265/NR/NINR NIH HHS/United States ; }, mesh = {Air Pollution/*adverse effects ; Arsenic/*adverse effects ; Asian People/*statistics &amp; numerical data ; Bacterial Infections/*epidemiology ; Bangladesh/epidemiology ; Cardiovascular Diseases/epidemiology ; Chronic Disease ; Environmental Exposure/*adverse effects ; Female ; Hepatitis B/epidemiology ; Hepatitis C/epidemiology ; Humans ; Inflammation/ethnology ; Male ; Microbiota ; Neoplasms/epidemiology/pathology ; Public Health/*trends ; }, abstract = {This paper presents the results of the literature review conducted for the working group topic on inflammation, infection, exposure, and the human microbiome. Infection and chronic inflammation can elevate risk for cardiovascular disease and cancer. Environmental exposures common among South Asian (SA) subgroups, such as arsenic exposure among Bangladeshis and particulate matter air pollution among taxi drivers, also pose risks. This review explores the effects of exposure to arsenic and particulate matter, as well as other infections common among SAs, including human papillomavirus (HPV) and hepatitis B/C infection. Emerging research on the human microbiome, and the effect of microbiome changes on obesity and diabetes risk among SAs are also explored.}, }
@article {pmid28945201, year = {2017}, author = {Ohlemacher, SI and Giblin, DE and d'Avignon, DA and Stapleton, AE and Trautner, BW and Henderson, JP}, title = {Enterobacteria secrete an inhibitor of Pseudomonas virulence during clinical bacteriuria.}, journal = {The Journal of clinical investigation}, volume = {127}, number = {11}, pages = {4018-4030}, pmid = {28945201}, issn = {1558-8238}, support = {R01 DK111930/DK/NIDDK NIH HHS/United States ; U54CK000482/ACL/ACL HHS/United States ; P30 DK089507/DK/NIDDK NIH HHS/United States ; R01 DK088830/DK/NIDDK NIH HHS/United States ; P50 DK064540/DK/NIDDK NIH HHS/United States ; R01 DK099534/DK/NIDDK NIH HHS/United States ; P41 GM103422/GM/NIGMS NIH HHS/United States ; R21 DK092293/DK/NIDDK NIH HHS/United States ; U54 CK000609/CK/NCEZID CDC HHS/United States ; T32 AI007172/AI/NIAID NIH HHS/United States ; U54 CK000482/CK/NCEZID CDC HHS/United States ; UL1 TR002345/TR/NCATS NIH HHS/United States ; KL2 TR002346/TR/NCATS NIH HHS/United States ; UL1 TR000448/TR/NCATS NIH HHS/United States ; P41 RR000954/RR/NCRR NIH HHS/United States ; R56 DK111930/DK/NIDDK NIH HHS/United States ; }, mesh = {Antibiosis ; Bacteriuria/*microbiology ; Biosynthetic Pathways ; Escherichia coli Infections/metabolism/*microbiology ; Escherichia coli Proteins/physiology ; Humans ; Iron/metabolism ; Models, Molecular ; Molecular Conformation ; Pseudomonas aeruginosa/metabolism/*pathogenicity ; Siderophores/chemistry/*metabolism ; Urinary Tract Infections/metabolism/*microbiology ; Uropathogenic Escherichia coli/*physiology ; Virulence ; }, abstract = {Escherichia coli and other Enterobacteriaceae are among the most common pathogens of the human urinary tract. Among the genetic gains of function associated with urinary E. coli isolates is the Yersinia high pathogenicity island (HPI), which directs the biosynthesis of yersiniabactin (Ybt), a virulence-associated metallophore. Using a metabolomics approach, we found that E. coli and other Enterobacteriaceae expressing the Yersinia HPI also secrete escherichelin, a second metallophore whose chemical structure matches a known synthetic inhibitor of the virulence-associated pyochelin siderophore system in Pseudomonas aeruginosa. We detected escherichelin during clinical E. coli urinary tract infection (UTI) and experimental human colonization with a commensal, potentially probiotic E. coli bacteriuria strain. Escherichelin production by colonizing enterobacteria may help human hosts resist opportunistic infections by Pseudomonas and other pyochelin-expressing bacteria. This siderophore-based mechanism of microbial antagonism may be one of many elements contributing to the protective effects of the human microbiome. Future UTI-preventive probiotic strains may benefit by retaining the escherichelin biosynthetic capacity of the Yersinia HPI while eliminating the Ybt biosynthetic capacity.}, }
@article {pmid28943872, year = {2017}, author = {Hidalgo-Cantabrana, C and Moro-García, MA and Blanco-Míguez, A and Fdez-Riverola, F and Lourenço, A and Alonso-Arias, R and Sánchez, B}, title = {In Silico Screening of the Human Gut Metaproteome Identifies Th17-Promoting Peptides Encrypted in Proteins of Commensal Bacteria.}, journal = {Frontiers in microbiology}, volume = {8}, number = {}, pages = {1726}, pmid = {28943872}, issn = {1664-302X}, abstract = {Scientific studies focused on the role of the human microbiome over human health have generated billions of gigabits of genetic information during the last decade. Nowadays integration of all this information in public databases and development of pipelines allowing us to biotechnologically exploit this information are urgently needed. Prediction of the potential bioactivity of the products encoded by the human gut microbiome, or metaproteome, is the first step for identifying proteins responsible for the molecular interaction between microorganisms and the immune system. We have recently published the Mechanism of Action of the Human Microbiome (MAHMI) database (http://www.mahmi.org), conceived as a resource compiling peptide sequences with a potential immunomodulatory activity. Fifteen out of the 300 hundred million peptides contained in the MAHMI database were synthesized. These peptides were identified as being encrypted in proteins produced by gut microbiota members, they do not contain cleavage points for the major intestinal endoproteases and displayed high probability to have immunomodulatory bioactivity. The bacterial peptides FR-16 and LR-17 encrypted in proteins from Bifidobacterium longum DJ010A and Bifidobacterium fragilis YCH46 respectively, showed the higher immune modulation capability over human peripheral blood mononuclear cells. Both peptides modulated the immune response toward increases in the Th17 and decreases in the Th1 cell response, together with an induction of IL-22 production. These results strongly suggest the combined use of bioinformatics and in vitro tools as a first stage in the screening of bioactive peptides encrypted in the human gut metaproteome.}, }
@article {pmid28938903, year = {2017}, author = {O'Hara, NB and Reed, HJ and Afshinnekoo, E and Harvin, D and Caplan, N and Rosen, G and Frye, B and Woloszynek, S and Ounit, R and Levy, S and Butler, E and Mason, CE}, title = {Metagenomic characterization of ambulances across the USA.}, journal = {Microbiome}, volume = {5}, number = {1}, pages = {125}, pmid = {28938903}, issn = {2049-2618}, support = {R01 AI125416/AI/NIAID NIH HHS/United States ; }, mesh = {*Ambulances ; Bacteria/classification/genetics/*isolation &amp; purification/pathogenicity ; Cross Infection/microbiology ; Genome, Bacterial ; High-Throughput Nucleotide Sequencing ; Hospitals ; Humans ; *Metagenome ; *Metagenomics ; *Microbial Consortia/genetics ; *Microbiota/genetics ; United States ; }, abstract = {BACKGROUND: Microbial communities in our built environments have great influence on human health and disease. A variety of built environments have been characterized using a metagenomics-based approach, including some healthcare settings. However, there has been no study to date that has used this approach in pre-hospital settings, such as ambulances, an important first point-of-contact between patients and hospitals.<br><br>RESULTS: We sequenced 398 samples from 137 ambulances across the USA using shotgun sequencing. We analyzed these data to explore the microbial ecology of ambulances including characterizing microbial community composition, nosocomial pathogens, patterns of diversity, presence of functional pathways and antimicrobial resistance, and potential spatial and environmental factors that may contribute to community composition. We found that the top 10 most abundant species are either common built environment microbes, microbes associated with the human microbiome (e.g., skin), or are species associated with nosocomial infections. We also found widespread evidence of antimicrobial resistance markers (hits ~&#x2009;90% samples). We identified six factors that may influence the microbial ecology of ambulances including ambulance surfaces, geographical-related factors (including region, longitude, and latitude), and weather-related factors (including temperature and precipitation).<br><br>CONCLUSIONS: While the vast majority of microbial species classified were beneficial, we also found widespread evidence of species associated with nosocomial infections and antimicrobial resistance markers. This study indicates that metagenomics may be useful to characterize the microbial ecology of pre-hospital ambulance settings and that more rigorous testing and cleaning of ambulances may be warranted.}, }
@article {pmid28915922, year = {2017}, author = {Winglee, K and Howard, AG and Sha, W and Gharaibeh, RZ and Liu, J and Jin, D and Fodor, AA and Gordon-Larsen, P}, title = {Recent urbanization in China is correlated with a Westernized microbiome encoding increased virulence and antibiotic resistance genes.}, journal = {Microbiome}, volume = {5}, number = {1}, pages = {121}, pmid = {28915922}, issn = {2049-2618}, support = {R01 DK104371/DK/NIDDK NIH HHS/United States ; R01 HL108427/HL/NHLBI NIH HHS/United States ; R24 HD050924/HD/NICHD NIH HHS/United States ; UL1 TR001111/TR/NCATS NIH HHS/United States ; P30 ES010126/ES/NIEHS NIH HHS/United States ; }, mesh = {Aged ; Bacteria/*genetics/pathogenicity ; China ; *Diet, Western ; Drug Resistance, Microbial/*genetics ; Escherichia coli/genetics/pathogenicity ; Feeding Behavior ; Female ; *Gastrointestinal Microbiome/genetics ; Genetic Variation ; High-Throughput Nucleotide Sequencing ; Humans ; Male ; *Metabolome ; Metagenomics ; Middle Aged ; Shigella/genetics/pathogenicity ; *Urbanization ; Virulence/genetics ; }, abstract = {BACKGROUND: Urbanization is associated with an increased risk for a number of diseases, including obesity, diabetes, and cancer, which all also show associations with the microbiome. While microbial community composition has been shown to vary across continents and in traditional versus Westernized societies, few studies have examined urban-rural differences in neighboring communities within a single country undergoing rapid urbanization. In this study, we compared the gut microbiome, plasma metabolome, dietary habits, and health biomarkers of rural and urban people from a single Chinese province.<br><br>RESULTS: We identified significant differences in the microbiota and microbiota-related plasma metabolites in rural versus recently urban subjects from the Hunan province of China. Microbes with higher relative abundance in Chinese urban samples have been associated with disease in other studies and were substantially more prevalent in the Human Microbiome Project cohort of American subjects. Furthermore, using whole metagenome sequencing, we found that urbanization was associated with a loss of microbial diversity and changes in the relative abundances of Viruses, Archaea, and Bacteria. Gene diversity, however, increased with urbanization, along with the proportion of reads associated with antibiotic resistance and virulence, which were strongly correlated with the presence of Escherichia and Shigella.<br><br>CONCLUSIONS: Our data suggest that urbanization has produced convergent evolution of the gut microbial composition in American and urban Chinese populations, resulting in similar compositional patterns of abundant microbes through similar lifestyles on different continents, including a loss of potentially beneficial bacteria and an increase in potentially harmful genes via increased relative abundance of Escherichia and Shigella.}, }
@article {pmid28912952, year = {2017}, author = {Pham, TP and Tidjani Alou, M and Traore, SI and Brah, S and Ali Diallo, B and Diallo, A and Sokhna, C and Baptiste, E and Levasseur, A and Fournier, PE and Cadoret, F and Raoult, D}, title = {Noncontiguous finished genome sequences and descriptions of 'Paenibacillus bouchesdurhonensis,' 'Paenibacillus rubinfantis,' 'Paenibacillus senegalimassiliensis' and 'Paenibacillus tuaregi' identified by culturomics.}, journal = {New microbes and new infections}, volume = {20}, number = {}, pages = {1-13}, pmid = {28912952}, issn = {2052-2975}, abstract = {Microbial culturomics represents a completely new approach to investigate microbial diversity by using different optimized culture conditions, mass spectrometry, genome sequencing and annotation and phenotypic description that allow for an extensive characterization of new species and the study of the human microbiome. Here we present four new species within the genus Paenibacillus: 'Paenibacillus bouchesdurhonensis' strain Marseille-P3071[T], 'Paenibacillus rubinfantis' strain MT18[T], 'Paenibacillus senegalimassiliensis' strain SIT18[T] and 'Paenibacillus tuaregi' strain Marseille-P2472[T], which are all facultatively aerobic and Gram-positive bacilli.}, }
@article {pmid28912600, year = {2017}, author = {Valencia, PM and Richard, M and Brock, J and Boglioli, E}, title = {The human microbiome: opportunity or hype?.}, journal = {Nature reviews. Drug discovery}, volume = {16}, number = {12}, pages = {823-824}, doi = {10.1038/nrd.2017.154}, pmid = {28912600}, issn = {1474-1784}, }
@article {pmid28910638, year = {2017}, author = {Verster, AJ and Ross, BD and Radey, MC and Bao, Y and Goodman, AL and Mougous, JD and Borenstein, E}, title = {The Landscape of Type VI Secretion across Human Gut Microbiomes Reveals Its Role in Community Composition.}, journal = {Cell host &amp; microbe}, volume = {22}, number = {3}, pages = {411-419.e4}, pmid = {28910638}, issn = {1934-6069}, support = {DP2 AT007802/AT/NCCIH NIH HHS/United States ; R35 GM118159/GM/NIGMS NIH HHS/United States ; UL1 TR001863/TR/NCATS NIH HHS/United States ; R01 AI080609/AI/NIAID NIH HHS/United States ; /HHMI_/Howard Hughes Medical Institute/United States ; }, mesh = {Adolescent ; Adult ; Bacteria/classification/genetics/isolation &amp; purification/*metabolism ; Bacterial Proteins/genetics/*metabolism ; Bacteroides/classification/genetics/isolation &amp; purification/metabolism ; Biodiversity ; Female ; *Gastrointestinal Microbiome ; Gastrointestinal Tract/*microbiology ; Humans ; Male ; Middle Aged ; Phylogeny ; Type VI Secretion Systems/genetics/*metabolism ; Young Adult ; }, abstract = {Although gut microbiome composition is well defined, the mechanisms underlying community assembly remain poorly understood. Bacteroidales possess three genetic architectures (GA1-3) of the type VI secretion system (T6SS), an effector delivery pathway that mediates interbacterial competition. Here we define the distribution and role of GA1-3 in the human gut using metagenomic analysis. We find that adult microbiomes harbor limited effector and cognate immunity genes, suggesting selection for compatibility at the species (GA1 and GA2) and strain (GA3) levels. Bacteroides fragilis GA3 is known to mediate potent inter-strain competition, and we observe GA3 enrichment among strains colonizing infant microbiomes, suggesting competition early in life. Additionally, GA3 is associated with increased Bacteroides abundance, indicating that this system confers an advantage in Bacteroides-rich ecosystems. Collectively, these analyses uncover the prevalence of T6SS-dependent competition and reveal its potential role in shaping human gut microbial composition.}, }
@article {pmid28910633, year = {2017}, author = {Gomez, A and Espinoza, JL and Harkins, DM and Leong, P and Saffery, R and Bockmann, M and Torralba, M and Kuelbs, C and Kodukula, R and Inman, J and Hughes, T and Craig, JM and Highlander, SK and Jones, MB and Dupont, CL and Nelson, KE}, title = {Host Genetic Control of the Oral Microbiome in Health and Disease.}, journal = {Cell host &amp; microbe}, volume = {22}, number = {3}, pages = {269-278.e3}, pmid = {28910633}, issn = {1934-6069}, support = {R01 DE019665/DE/NIDCR NIH HHS/United States ; }, mesh = {Age Factors ; Bacteria/classification/genetics/*isolation &amp; purification ; Child ; Child, Preschool ; Dental Caries/*genetics/*microbiology ; Ecosystem ; Female ; Genetic Predisposition to Disease ; Genotype ; Humans ; Male ; *Microbiota ; Mouth/*microbiology ; Phylogeny ; Twins/genetics ; }, abstract = {Host-associated microbial communities are influenced by both host genetics and environmental factors. However, factors controlling the human oral microbiome and their impact on disease remain to be investigated. To determine the combined and relative effects of host genotype and environment on oral microbiome composition and caries phenotypes, we profiled the supragingival plaque microbiome of 485 dizygotic and monozygotic twins aged 5-11. Oral microbiome similarity always increased with shared host genotype, regardless of caries state. Additionally, although most of the variation in the oral microbiome was determined by environmental factors, highly heritable oral taxa were identified. The most heritable oral bacteria were not associated with caries state, did not tend to co-occur with other taxa, and decreased in abundance with age and sugar consumption frequency. Thus, while the human oral microbiome composition is influenced by host genetic background, potentially cariogenic taxa are likely not controlled by genetic factors.}, }
@article {pmid28905671, year = {2018}, author = {Prokopienko, AJ and Nolin, TD}, title = {Microbiota-derived uremic retention solutes: perpetrators of altered nonrenal drug clearance in kidney disease.}, journal = {Expert review of clinical pharmacology}, volume = {11}, number = {1}, pages = {71-82}, pmid = {28905671}, issn = {1751-2441}, support = {R01 GM107122/GM/NIGMS NIH HHS/United States ; TL1 TR001858/TR/NCATS NIH HHS/United States ; }, mesh = {Animals ; Cresols/metabolism ; Drug-Related Side Effects and Adverse Reactions/metabolism ; Dysbiosis/complications ; Gastrointestinal Microbiome/*physiology ; Humans ; Indican/metabolism ; Kidney Diseases/*physiopathology ; Liver/enzymology/metabolism ; Pharmaceutical Preparations/metabolism ; Sulfuric Acid Esters/metabolism ; Toxins, Biological/*metabolism ; }, abstract = {Scientific interest in the gut microbiota is increasing due to improved understanding of its implications in human health and disease. In patients with kidney disease, gut microbiota-derived uremic toxins directly contribute to altered nonrenal drug clearance. Microbial imbalances, known as dysbiosis, potentially increase formation of microbiota-derived toxins, and diminished renal clearance leads to toxin accumulation. High concentrations of microbiota-derived toxins such as indoxyl sulfate and p-cresol sulfate perpetrate interactions with drug metabolizing enzymes and transporters, which provides a mechanistic link between increases in drug-related adverse events and dysbiosis in kidney disease. Areas covered: This review summarizes the effects of microbiota-derived uremic toxins on hepatic phase I and phase II drug metabolizing enzymes and drug transporters. Research articles that tested individual toxins were included. Therapeutic strategies to target microbial toxins are also discussed. Expert commentary: Large interindividual variability in toxin concentrations may explain some differences in nonrenal clearance of medications. Advances in human microbiome research provide unique opportunities to systematically evaluate the impact of individual and combined microbial toxins on drug metabolism and transport, and to explore microbiota-derived uremic toxins as potential therapeutic targets.}, }
@article {pmid28900019, year = {2017}, author = {Shaw, L and Ribeiro, ALR and Levine, AP and Pontikos, N and Balloux, F and Segal, AW and Roberts, AP and Smith, AM}, title = {The Human Salivary Microbiome Is Shaped by Shared Environment Rather than Genetics: Evidence from a Large Family of Closely Related Individuals.}, journal = {mBio}, volume = {8}, number = {5}, pages = {}, pmid = {28900019}, issn = {2150-7511}, support = {MR/L000261/1/MRC_/Medical Research Council/United Kingdom ; MR/P007597/1/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Adult ; Bacteria/genetics ; Cohort Studies ; *Environment ; *Family ; Family Characteristics/ethnology ; Female ; Geography ; Humans ; Male ; *Microbiota/genetics ; Mouth/microbiology ; Polymorphism, Single Nucleotide ; Saliva/*microbiology ; }, abstract = {The human microbiome is affected by multiple factors, including the environment and host genetics. In this study, we analyzed the salivary microbiomes of an extended family of Ashkenazi Jewish individuals living in several cities and investigated associations with both shared household and host genetic similarities. We found that environmental effects dominated over genetic effects. While there was weak evidence of geographical structuring at the level of cities, we observed a large and significant effect of shared household on microbiome composition, supporting the role of the immediate shared environment in dictating the presence or absence of taxa. This effect was also seen when including adults who had grown up in the same household but moved out prior to the time of sampling, suggesting that the establishment of the salivary microbiome earlier in life may affect its long-term composition. We found weak associations between host genetic relatedness and microbiome dissimilarity when using family pedigrees as proxies for genetic similarity. However, this association disappeared when using more-accurate measures of kinship based on genome-wide genetic markers, indicating that the environment rather than host genetics is the dominant factor affecting the composition of the salivary microbiome in closely related individuals. Our results support the concept that there is a consistent core microbiome conserved across global scales but that small-scale effects due to a shared living environment significantly affect microbial community composition.IMPORTANCE Previous research shows that the salivary microbiomes of relatives are more similar than those of nonrelatives, but it remains difficult to distinguish the effects of relatedness and shared household environment. Furthermore, pedigree measures may not accurately measure host genetic similarity. In this study, we include genetic relatedness based on genome-wide single nucleotide polymorphisms (SNPs) (rather than pedigree measures) and shared environment in the same analysis. We quantify the relative importance of these factors by studying the salivary microbiomes in members of a large extended Ashkenazi Jewish family living in different locations. We find that host genetics plays no significant role and that the dominant factor is the shared environment at the household level. We also find that this effect appears to persist in individuals who have moved out of the parental household, suggesting that aspects of salivary microbiome composition established during upbringing can persist over a time scale of years.}, }
@article {pmid28899789, year = {2017}, author = {Rózsa, L and Apari, P and Sulyok, M and Tappe, D and Bodó, I and Hardi, R and Müller, V}, title = {The evolutionary logic of sepsis.}, journal = {Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases}, volume = {55}, number = {}, pages = {135-141}, doi = {10.1016/j.meegid.2017.09.006}, pmid = {28899789}, issn = {1567-7257}, mesh = {Animals ; *Biological Evolution ; Disease Susceptibility ; *Host-Pathogen Interactions ; Humans ; Microbiota ; Sepsis/*etiology/transmission ; Virulence ; }, abstract = {The recently proposed Microbiome Mutiny Hypothesis posits that members of the human microbiome obtain information about the host individuals' health status and, when host survival is compromised, switch to an intensive exploitation strategy to maximize residual transmission. In animals and humans, sepsis is an acute systemic reaction to microbes invading the normally sterile body compartments. When induced by formerly mutualistic or neutral microbes, possibly in response to declining host health, sepsis appears to fit the 'microbiome mutiny' scenario except for its apparent failure to enhance transmission of the causative organisms. We propose that the ability of certain species of the microbiome to induce sepsis is not a fortuitous side effect of within-host replication, but rather it might, in some cases, be the result of their adaptive evolution. Whenever host health declines, inducing sepsis can be adaptive for those members of the healthy human microbiome that are capable of colonizing the future cadaver and spread by cadaver-borne transmission. We hypothesize that such microbes might exhibit switches along the 'mutualist - lethal pathogen - decomposer - mutualist again' scenario, implicating a previously unsuspected, surprising level of phenotypic plasticity. This hypothesis predicts that those species of the healthy microbiome that are recurring causative agents of sepsis can participate in the decomposition of cadavers, and can be transmitted as soil-borne or water-borne infections. Furthermore, in individual sepsis cases, the same microbial clones that dominate the systemic infection that precipitates sepsis, should also be present in high concentration during decomposition following death: this prediction is testable by molecular fingerprinting in experimentally induced animal models. Sepsis is a leading cause of human death worldwide. If further research confirms that some cases of sepsis indeed involve the 'mutiny' (facultative phenotypic switching) of normal members of the microbiome, then new strategies could be devised to prevent or treat sepsis by interfering with this process.}, }
@article {pmid28887423, year = {2017}, author = {Schmedes, SE and Woerner, AE and Budowle, B}, title = {Forensic Human Identification Using Skin Microbiomes.}, journal = {Applied and environmental microbiology}, volume = {83}, number = {22}, pages = {}, pmid = {28887423}, issn = {1098-5336}, abstract = {The human microbiome contributes significantly to the genetic content of the human body. Genetic and environmental factors help shape the microbiome, and as such, the microbiome can be unique to an individual. Previous studies have demonstrated the potential to use microbiome profiling for forensic applications; however, a method has yet to identify stable features of skin microbiomes that produce high classification accuracies for samples collected over reasonably long time intervals. A novel approach is described here to classify skin microbiomes to their donors by comparing two feature types: Propionibacterium acnes pangenome presence/absence features and nucleotide diversities of stable clade-specific markers. Supervised learning was used to attribute skin microbiomes from 14 skin body sites from 12 healthy individuals sampled at three time points over a >2.5-year period with accuracies of up to 100% for three body sites. Feature selection identified a reduced subset of markers from each body site that are highly individualizing, identifying 187 markers from 12 clades. Classification accuracies were compared in a formal model testing framework, and the results of this analysis indicate that learners trained on nucleotide diversity perform significantly better than those trained on presence/absence encodings. This study used supervised learning to identify individuals with high accuracy and associated stable features from skin microbiomes over a period of up to almost 3 years. These selected features provide a preliminary marker panel for future development of a robust and reproducible method for skin microbiome profiling for forensic human identification.IMPORTANCE A novel approach is described to attribute skin microbiomes, collected over a period of >2.5 years, to their individual hosts with a high degree of accuracy. Nucleotide diversities of stable clade-specific markers with supervised learning were used to classify skin microbiomes from a particular individual with up to 100% classification accuracy for three body sites. Attribute selection was used to identify 187 genetic markers from 12 clades which provide the greatest differentiation of individual skin microbiomes from 14 skin sites. This study performs skin microbiome profiling from a supervised learning approach and obtains high classification accuracy for samples collected from individuals over a relatively long time period for potential application to forensic human identification.}, }
@article {pmid28874411, year = {2018}, author = {Méndez-García, C and Barbas, C and Ferrer, M and Rojo, D}, title = {Complementary Methodologies To Investigate Human Gut Microbiota in Host Health, Working towards Integrative Systems Biology.}, journal = {Journal of bacteriology}, volume = {200}, number = {3}, pages = {}, pmid = {28874411}, issn = {1098-5530}, mesh = {Animals ; Feces/microbiology ; *Gastrointestinal Microbiome ; Health ; Homeostasis ; Humans ; Systems Biology/*methods ; }, abstract = {In 1680, Antonie van Leeuwenhoek noted compositional differences in his oral and fecal microbiota, pioneering the study of the diversity of the human microbiome. From Leeuwenhoek's time to successful modern attempts at changing the gut microbial landscape to cure disease, there has been an exponential increase in the recognition of our resident microbes as part of ourselves. Thus, the human host and microbiome have evolved in parallel to configure a balanced system in which microbes survive in homeostasis with our innate and acquired immune systems, unless disease occurs. A growing number of studies have demonstrated a correlation between the presence/absence of microbial taxa and some of their functional molecules (i.e., genes, proteins, and metabolites) with health and disease states. Nevertheless, misleading experimental design on human subjects and the cost and lack of standardized animal models pose challenges to answering the question of whether changes in microbiome composition are cause or consequence of a certain biological state. In this review, we evaluate the state of the art of methodologies that enable the study of the gut microbiome, encouraging a change in broadly used analytic strategies by choosing effector molecules (proteins and metabolites) in combination with coding nucleic acids. We further explore microbial and effector microbial product imbalances that relate to disease and health.}, }
@article {pmid28872698, year = {2017}, author = {Zhang, Y and Han, SW and Cox, LM and Li, H}, title = {A multivariate distance-based analytic framework for microbial interdependence association test in longitudinal study.}, journal = {Genetic epidemiology}, volume = {41}, number = {8}, pages = {769-778}, pmid = {28872698}, issn = {1098-2272}, support = {R01 DK090989/DK/NIDDK NIH HHS/United States ; R01 DK110014/DK/NIDDK NIH HHS/United States ; U01 CA170948/CA/NCI NIH HHS/United States ; U01 CA182370/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Bacteria/drug effects/genetics/growth &amp; development ; Bifidobacterium/drug effects/genetics/growth &amp; development ; DNA, Bacterial/chemistry/genetics ; High-Throughput Nucleotide Sequencing ; Humans ; Internet ; Intestines/*microbiology ; Longitudinal Studies ; Mice ; *Microbiota ; *Models, Genetic ; Penicillins/pharmacology ; Sequence Analysis, DNA ; User-Computer Interface ; }, abstract = {Human microbiome is the collection of microbes living in and on the various parts of our body. The microbes living on our body in nature do not live alone. They act as integrated microbial community with massive competing and cooperating and contribute to our human health in a very important way. Most current analyses focus on examining microbial differences at a single time point, which do not adequately capture the dynamic nature of the microbiome data. With the advent of high-throughput sequencing and analytical tools, we are able to probe the interdependent relationship among microbial species through longitudinal study. Here, we propose a multivariate distance-based test to evaluate the association between key phenotypic variables and microbial interdependence utilizing the repeatedly measured microbiome data. Extensive simulations were performed to evaluate the validity and efficiency of the proposed method. We also demonstrate the utility of the proposed test using a well-designed longitudinal murine experiment and a longitudinal human study. The proposed methodology has been implemented in the freely distributed open-source R package and Python code.}, }
@article {pmid28866243, year = {2018}, author = {Heeney, DD and Gareau, MG and Marco, ML}, title = {Intestinal Lactobacillus in health and disease, a driver or just along for the ride?.}, journal = {Current opinion in biotechnology}, volume = {49}, number = {}, pages = {140-147}, pmid = {28866243}, issn = {1879-0429}, support = {R01 AT009365/AT/NCCIH NIH HHS/United States ; }, mesh = {Animals ; Behavior ; Biodiversity ; Cognition ; *Disease ; *Health ; Humans ; Intestines/*microbiology ; Lactobacillus/*physiology ; }, abstract = {Metagenomics and related methods have led to significant advances in our understanding of the human microbiome. Members of the genus Lactobacillus, although best understood for essential roles in food fermentations and applications as probiotics, have also come to the fore in a number of untargeted gut microbiome studies in humans and animals. Even though Lactobacillus is only a minor member of the human colonic microbiota, the proportions of those bacteria are frequently either positively or negatively correlated with human disease and chronic conditions. Recent findings on Lactobacillus species in human and animal microbiome research, together with the increased knowledge on probiotic and other ingested lactobacilli, have resulted in new perspectives on the importance of this genus to human health.}, }
@article {pmid28856733, year = {2017}, author = {Barr, JJ}, title = {A bacteriophages journey through the human body.}, journal = {Immunological reviews}, volume = {279}, number = {1}, pages = {106-122}, doi = {10.1111/imr.12565}, pmid = {28856733}, issn = {1600-065X}, mesh = {Animals ; Bacteria/*virology ; Bacteriophages/*immunology ; Homeostasis ; Human Body ; Humans ; Immune System/microbiology/*virology ; Intestines/microbiology/*virology ; *Microbiota ; Mucous Membrane/microbiology/*virology ; }, abstract = {The human body is colonized by a diverse collective of microorganisms, including bacteria, fungi, protozoa and viruses. The smallest entity of this microbial conglomerate are the bacterial viruses. Bacteriophages, or phages for short, exert significant selective pressure on their bacterial hosts, undoubtedly influencing the human microbiome and its impact on our health and well-being. Phages colonize all niches of the body, including the skin, oral cavity, lungs, gut, and urinary tract. As such our bodies are frequently and continuously exposed to diverse collections of phages. Despite the prevalence of phages throughout our bodies, the extent of their interactions with human cells, organs, and immune system is still largely unknown. Phages physically interact with our mucosal surfaces, are capable of bypassing epithelial cell layers, disseminate throughout the body and may manipulate our immune system. Here, I establish the novel concept of an "intra-body phageome," which encompasses the collection of phages residing within the classically "sterile" regions of the body. This review will take a phage-centric view of the microbiota, human body, and immune system with the ultimate goal of inspiring a greater appreciation for both the indirect and direct interactions between bacteriophages and their mammalian hosts.}, }
@article {pmid28846702, year = {2017}, author = {Abdelmaksoud, AA and Girerd, PH and Garcia, EM and Brooks, JP and Leftwich, LM and Sheth, NU and Bradley, SP and Serrano, MG and Fettweis, JM and Huang, B and Strauss, JF and Buck, GA and Jefferson, KK}, title = {Association between statin use, the vaginal microbiome, and Gardnerella vaginalis vaginolysin-mediated cytotoxicity.}, journal = {PloS one}, volume = {12}, number = {8}, pages = {e0183765}, pmid = {28846702}, issn = {1932-6203}, support = {P60 MD002256/MD/NIMHD NIH HHS/United States ; U54 DE023786/DE/NIDCR NIH HHS/United States ; UH3 AI083263/AI/NIAID NIH HHS/United States ; }, mesh = {Bacterial Proteins/*physiology ; Bacterial Toxins ; Cell Survival/*physiology ; Colony Count, Microbial ; Epithelial Cells/metabolism ; Female ; Gardnerella vaginalis/isolation &amp; purification/*metabolism ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/*pharmacology ; Microbiota/*drug effects/genetics ; Middle Aged ; RNA, Ribosomal, 16S/genetics ; Simvastatin/*pharmacology ; Vagina/*microbiology ; }, abstract = {BACKGROUND: Bacterial vaginosis (BV) is the leading dysbiosis of the vaginal microbiome. The pathways leading towards the development of BV are not well understood. Gardnerella vaginalis is frequently associated with BV. G. vaginalis produces the cholesterol-dependent cytolysin (CDC), vaginolysin, which can lyse a variety of human cells and is thought to play a role in pathogenesis. Because membrane cholesterol is required for vaginolysin to function, and because HMG-CoA reductase inhibitors (statins) affect not only serum levels of cholesterol but membrane levels as well, we hypothesized that statins might affect the vaginal microbiome.<br><br>METHODS: To investigate the relationship between use of the statins and the vaginal microbiome, we analyzed 16S rRNA gene taxonomic surveys performed on vaginal samples from 133 women who participated in the Vaginal Human Microbiome Project and who were taking statins at the time of sampling, 152 women who reported high cholesterol levels but were not taking statins, and 316 women who did not report high cholesterol. To examine the effect of statins on the cytolytic effect of vaginolysin, the cholesterol-dependent cytolysin (CDC) produced by Gardnerella vaginalis, we assessed the effect of simvastatin pretreatment of VK2E6/E7 vaginal epithelial cells on vaginolysin-mediated cytotoxicity.<br><br>RESULTS: The mean proportion of G. vaginalis among women taking statins was significantly lower relative to women not using statins. Women using statins had higher mean proportions of Lactobacillus crispatus relative to women with normal cholesterol levels, and higher levels of Lactobacillus jensenii relative to women with high cholesterol but not taking statins. In vitro, vaginal epithelial cells pretreated with simvastatin were relatively resistant to vaginolysin and this effect was inhibited by cholesterol.<br><br>CONCLUSIONS: In this cross-sectional study, statin use was associated with reduced proportions of G. vaginalis and greater proportions of beneficial lactobacilli within the vaginal microbiome. The negative association between statin use and G. vaginalis may be related to inhibition of vaginolysin function.}, }
@article {pmid28845973, year = {2018}, author = {Chu, J and Vila-Farres, X and Inoyama, D and Gallardo-Macias, R and Jaskowski, M and Satish, S and Freundlich, JS and Brady, SF}, title = {Human Microbiome Inspired Antibiotics with Improved β-Lactam Synergy against MDR Staphylococcus aureus.}, journal = {ACS infectious diseases}, volume = {4}, number = {1}, pages = {33-38}, pmid = {28845973}, issn = {2373-8227}, support = {U19 AI109713/AI/NIAID NIH HHS/United States ; }, mesh = {Anti-Bacterial Agents/*pharmacology ; Bacterial Proteins/chemistry/genetics ; *Drug Discovery ; Drug Resistance, Multiple, Bacterial/*drug effects/genetics ; Drug Synergism ; Humans ; Methicillin-Resistant Staphylococcus aureus/drug effects/genetics ; Microbial Sensitivity Tests ; *Microbiota ; Models, Molecular ; Mutation ; Phospholipid Transfer Proteins/chemistry/genetics ; Staphylococcus aureus/*drug effects/genetics ; Structure-Activity Relationship ; beta-Lactams/*pharmacology ; }, abstract = {The flippase MurJ is responsible for transporting the cell wall intermediate lipid II from the cytoplasm to the outside of the cell. While essential for the survival of bacteria, it remains an underexploited target for antibacterial therapy. The humimycin antibiotics are lipid II flippase (MurJ) inhibitors that were synthesized on the basis of bioinformatic predictions derived from secondary metabolite gene clusters found in the human microbiome. Here, we describe an SAR campaign around humimycin A that produced humimycin 17S. Compared to humimycin A, 17S is a more potent β-lactam potentiator, has a broader spectrum of activity, which now includes both methicillin resistant Staphylococcus aureus (MRSA) and vancomycin resistant Enterococcus faecalis (VRE), and did not lead to any detectable resistance when used in combination with a β-lactam. Combinations of β-lactam and humimycin 17S provide a potentially useful long-term MRSA regimen.}, }
@article {pmid28842845, year = {2017}, author = {Li, DY and Tang, WHW}, title = {Gut Microbiota and Atherosclerosis.}, journal = {Current atherosclerosis reports}, volume = {19}, number = {10}, pages = {39}, doi = {10.1007/s11883-017-0675-9}, pmid = {28842845}, issn = {1534-6242}, mesh = {Animals ; *Atherosclerosis/drug therapy/metabolism/microbiology ; Bile Acids and Salts/metabolism ; Carnitine/metabolism ; Diet ; Disease Models, Animal ; *Gastrointestinal Microbiome/immunology ; Humans ; Methylamines/*metabolism ; }, abstract = {PURPOSE OF REVIEW: Studies in microbiota-mediated health risks have gained traction in recent years since the compilation of the Human Microbiome Project. No longer do we believe that our gut microbiota is an inert set of microorganisms that reside in the body without consequence. In this review, we discuss the recent findings which further our understanding of the connection between the gut microbiota and the atherosclerosis.<br><br>RECENT FINDINGS: We evaluate studies which illustrate the current understanding of the relationship between infection, immunity, altered metabolism, and bacterial products such as immune activators or dietary metabolites and their contributions to the development of atherosclerosis. In particular, we critically examine rec ent clinical and mechanistic findings for the novel microbiota-dependent dietary metabolite, trimethylamine N-oxide (TMAO), which has been implicated in atherosclerosis. These discoveries are now becoming integrated with advances in microbiota profiling which enhance our ability to interrogate the functional role of the gut microbiome and develop strategies for targeted therapeutics. The gut microbiota is a multi-faceted system that is unraveling novel contributors to the development and progression of atherosclerosis. In this review, we discuss historic and novel contributors while highlighting the TMAO story mainly as an example of the various paths taken beyond deciphering microbial composition to elucidate downstream mechanisms that promote (or protect from) atherogenesis in the hopes of translating these findings from bench to bedside.}, }
@article {pmid28841398, year = {2018}, author = {Chanyi, RM}, title = {The complete microbiologist, Dr. Terry Beveridge.}, journal = {Canadian journal of microbiology}, volume = {64}, number = {9}, pages = {643}, doi = {10.1139/cjm-2017-0465}, pmid = {28841398}, issn = {1480-3275}, }
@article {pmid28837464, year = {2017}, author = {Clark, AP}, title = {The Human Microbiome.}, journal = {The American journal of nursing}, volume = {117}, number = {9}, pages = {13}, doi = {10.1097/01.NAJ.0000524523.42427.40}, pmid = {28837464}, issn = {1538-7488}, mesh = {Humans ; *Microbiota ; }, }
@article {pmid28837129, year = {2017}, author = {Beghini, F and Pasolli, E and Truong, TD and Putignani, L and Cacciò, SM and Segata, N}, title = {Large-scale comparative metagenomics of Blastocystis, a common member of the human gut microbiome.}, journal = {The ISME journal}, volume = {11}, number = {12}, pages = {2848-2863}, pmid = {28837129}, issn = {1751-7370}, mesh = {Adolescent ; Adult ; Aged ; Blastocystis/classification/genetics/*isolation &amp; purification ; Crohn Disease/parasitology ; Dysbiosis/parasitology ; Feces/parasitology ; Female ; Gastrointestinal Tract/*parasitology ; Humans ; Male ; Metagenomics ; Middle Aged ; Prevalence ; Young Adult ; }, abstract = {The influence of unicellular eukaryotic microorganisms on human gut health and disease is still largely unexplored. Blastocystis spp. commonly colonize the gut, but its clinical significance and ecological role are currently unsettled. We have developed a high-sensitivity bioinformatic pipeline to detect Blastocystis subtypes (STs) from shotgun metagenomics, and applied it to 12 large data sets, comprising 1689 subjects of different geographic origin, disease status and lifestyle. We confirmed and extended previous observations on the high prevalence the microrganism in the population (14.9%), its non-random and ST-specific distribution, and its ability to cause persistent (asymptomatic) colonization. These findings, along with the higher prevalence observed in non-westernized individuals, the lack of positive association with any of the disease considered, and decreased presence in individuals with dysbiosis associated with colorectal cancer and Crohn's disease, strongly suggest that Blastocystis is a component of the healthy gut microbiome. Further, we found an inverse association between body mass index and Blastocystis, and strong co-occurrence with archaeal organisms (Methanobrevibacter smithii) and several bacterial species. The association of specific microbial community structures with Blastocystis was confirmed by the high predictability (up to 0.91 area under the curve) of the microorganism colonization based on the species-level composition of the microbiome. Finally, we reconstructed and functionally profiled 43 new draft Blastocystis genomes and discovered a higher intra subtype variability of ST1 and ST2 compared with ST3 and ST4. Altogether, we provide an in-depth epidemiologic, ecological, and genomic analysis of Blastocystis, and show how metagenomics can be crucial to advance population genomics of human parasites.}, }
@article {pmid28830999, year = {2017}, author = {Kowarsky, M and Camunas-Soler, J and Kertesz, M and De Vlaminck, I and Koh, W and Pan, W and Martin, L and Neff, NF and Okamoto, J and Wong, RJ and Kharbanda, S and El-Sayed, Y and Blumenfeld, Y and Stevenson, DK and Shaw, GM and Wolfe, ND and Quake, SR}, title = {Numerous uncharacterized and highly divergent microbes which colonize humans are revealed by circulating cell-free DNA.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {114}, number = {36}, pages = {9623-9628}, pmid = {28830999}, issn = {1091-6490}, mesh = {Cell-Free Nucleic Acids/*blood/*genetics ; DNA, Bacterial/*blood/*genetics ; DNA, Viral/*blood/*genetics ; Genetic Variation ; High-Throughput Nucleotide Sequencing/methods ; Humans ; Metagenomics/methods ; Microbiota/*genetics ; Phylogeny ; }, abstract = {Blood circulates throughout the human body and contains molecules drawn from virtually every tissue, including the microbes and viruses which colonize the body. Through massive shotgun sequencing of circulating cell-free DNA from the blood, we identified hundreds of new bacteria and viruses which represent previously unidentified members of the human microbiome. Analyzing cumulative sequence data from 1,351 blood samples collected from 188 patients enabled us to assemble 7,190 contiguous regions (contigs) larger than 1 kbp, of which 3,761 are novel with little or no sequence homology in any existing databases. The vast majority of these novel contigs possess coding sequences, and we have validated their existence both by finding their presence in independent experiments and by performing direct PCR amplification. When their nearest neighbors are located in the tree of life, many of the organisms represent entirely novel taxa, showing that microbial diversity within the human body is substantially broader than previously appreciated.}, }
@article {pmid28825919, year = {2017}, author = {Dunn, AB and Jordan, S and Baker, BJ and Carlson, NS}, title = {The Maternal Infant Microbiome: Considerations for Labor and Birth.}, journal = {MCN. The American journal of maternal child nursing}, volume = {42}, number = {6}, pages = {318-325}, pmid = {28825919}, issn = {1539-0683}, support = {F31 NR015400/NR/NINR NIH HHS/United States ; K01 NR016984/NR/NINR NIH HHS/United States ; R01 NR014800/NR/NINR NIH HHS/United States ; }, mesh = {Adolescent ; Adult ; Anti-Bacterial Agents/adverse effects/therapeutic use ; Cesarean Section/adverse effects ; Female ; Gastrointestinal Microbiome/*physiology ; Humans ; Infant, Newborn ; Maternal-Fetal Exchange/*physiology ; Mothers/statistics &amp; numerical data ; Parturition/physiology ; Pregnancy ; }, abstract = {The human microbiome plays a role in maintaining health, but is also thought to attenuate and exacerbate risk factors for adverse maternal-child health outcomes. The development of the microbiome begins in utero; however, factors related to the labor and birth environment have been shown to influence the initial colonization process of the newborn microbiome. This "seeding" or transfer of microbes from the mother to newborn may serve as an early inoculation process with implications for the long-term health outcomes of newborns. Studies have shown that there are distinct differences in the microbiome profiles of newborns born vaginally compared with those born by cesarean. Antibiotic exposure has been shown to alter the microbial profiles of women and may influence the gut microbial profiles of their newborns. Considering that the first major microbial colonization occurs at birth, it is essential that labor and birth nurses be aware of factors that may alter the composition of the microbiome during the labor and birth process. The implications of various activities and factors unique to the labor and birth environment that may influence the microbiome of women and newborns during the labor and birth process (e.g., route of birth, antibiotic use, nursing procedures) are presented with a focus on the role of labor nurses and the potential influence of nursing activities on this process.}, }
@article {pmid28824902, year = {2017}, author = {Agarwal, D and Dhotre, D and Patil, R and Shouche, Y and Juvekar, S and Salvi, S}, title = {Potential of Health and Demographic Surveillance System in Asthma and Chronic Obstructive Pulmonary Disease Microbiome Research.}, journal = {Frontiers in public health}, volume = {5}, number = {}, pages = {196}, pmid = {28824902}, issn = {2296-2565}, abstract = {Health and demographic surveillance system (HDSS) is a population-based health and vital event registration system that monitors demographic and health events in a geographically defined population at regular intervals. Human microbiome research in the past decade has been the field of increasingly intense research much due to its demonstrated impact upon various health conditions including human chronic airway diseases such as asthma and chronic obstructive pulmonary disease (COPD). Many confounding factors have been revealed to play a role in shaping the microbiome in chronic airway diseases. Asthma and COPD follows a typical pattern of disease progression, which includes stable and exacerbation state in which the microbiota is known to vary. However, many such studies lack extensive and longitudinal sampling with inadequate metadata, which has resulted in the inconsistencies in the observations. HDSS provides such a platform, which can offer a deeper understanding of the role of the microbiome in human health. In this review, we highlight opportunities and limitations in microbiome research with the help of studies conducted on chronic airway diseases like asthma and COPD. In addition, we also emphasize on the benefits of HDSS and future directions in lung microbiome research.}, }
@article {pmid28821012, year = {2017}, author = {Fukuyama, J and Rumker, L and Sankaran, K and Jeganathan, P and Dethlefsen, L and Relman, DA and Holmes, SP}, title = {Multidomain analyses of a longitudinal human microbiome intestinal cleanout perturbation experiment.}, journal = {PLoS computational biology}, volume = {13}, number = {8}, pages = {e1005706}, pmid = {28821012}, issn = {1553-7358}, support = {R01 AI112401/AI/NIAID NIH HHS/United States ; T15 LM007033/LM/NLM NIH HHS/United States ; }, mesh = {Adult ; DNA, Bacterial/analysis/genetics ; Diarrhea ; Female ; Gastrointestinal Microbiome/*genetics ; Humans ; Longitudinal Studies ; Male ; Metagenome/*genetics ; Metagenomics/*methods ; Middle Aged ; *Models, Biological ; Principal Component Analysis ; RNA, Ribosomal, 16S/genetics ; Young Adult ; }, abstract = {Our work focuses on the stability, resilience, and response to perturbation of the bacterial communities in the human gut. Informative flash flood-like disturbances that eliminate most gastrointestinal biomass can be induced using a clinically-relevant iso-osmotic agent. We designed and executed such a disturbance in human volunteers using a dense longitudinal sampling scheme extending before and after induced diarrhea. This experiment has enabled a careful multidomain analysis of a controlled perturbation of the human gut microbiota with a new level of resolution. These new longitudinal multidomain data were analyzed using recently developed statistical methods that demonstrate improvements over current practices. By imposing sparsity constraints we have enhanced the interpretability of the analyses and by employing a new adaptive generalized principal components analysis, incorporated modulated phylogenetic information and enhanced interpretation through scoring of the portions of the tree most influenced by the perturbation. Our analyses leverage the taxa-sample duality in the data to show how the gut microbiota recovers following this perturbation. Through a holistic approach that integrates phylogenetic, metagenomic and abundance information, we elucidate patterns of taxonomic and functional change that characterize the community recovery process across individuals. We provide complete code and illustrations of new sparse statistical methods for high-dimensional, longitudinal multidomain data that provide greater interpretability than existing methods.}, }
@article {pmid28819919, year = {2019}, author = {Houf, JR}, title = {The Microbial Mother Meets the Independent Organ: Cultural Discourses of Reproductive Microbiomes.}, journal = {The Journal of medical humanities}, volume = {40}, number = {3}, pages = {329-345}, pmid = {28819919}, issn = {1573-3645}, mesh = {Culture ; Genitalia/*microbiology ; Humans ; *Microbiota ; *Mothers ; *Reproduction ; Sex Factors ; }, abstract = {The human microbiome is changing the way experts and non-experts think about germs and microorganisms. This essay is a gender analysis of contemporary discourses surrounding the human reproductive microbiome, specifically the vaginal microbiota and the penile microbiota. I first historically situate the human reproductive microbiome within the germ theory of disease. Then, I draw on Heather Paxson's Foucauldian and Latourian concept of microbiopolitics to argue that microbiopolitics is not only about how humans should live with microorganisms; but it also impacts how humans and microbes live together as gendered beings. I illustrate this gendering through two figures: the microbial mother and the independent organ.}, }
@article {pmid28813450, year = {2017}, author = {Chen, H and Peng, S and Dai, L and Zou, Q and Yi, B and Yang, X and Ma, ZS}, title = {Oral microbial community assembly under the influence of periodontitis.}, journal = {PloS one}, volume = {12}, number = {8}, pages = {e0182259}, pmid = {28813450}, issn = {1932-6203}, mesh = {Algorithms ; *Biodiversity ; Case-Control Studies ; Datasets as Topic ; Humans ; Metagenome ; Metagenomics/methods ; *Microbiota ; Models, Theoretical ; Mouth Mucosa/*microbiology ; Periodontitis/*microbiology ; }, abstract = {Several ecological hypotheses (e.g., specific plaque, non-specific plaque and keystone pathogen) regarding the etiology of periodontitis have been proposed since the 1990s, most of which have been centered on the concept of dysbiosis associated with periodontitis. Nevertheless, none of the existing hypotheses have presented mechanistic interpretations on how and why dysbiosis actually occurs. Hubbell's neutral theory of biodiversity offers a powerful null model to test hypothesis regarding the mechanism of community assembly and diversity maintenance from the metagenomic sequencing data, which can help to understand the forces that shape the community dynamics such as dysbiosis. Here we reanalyze the dataset from Abusleme et al.'s comparative study of the oral microbial communities from periodontitis patients and healthy individuals. Our study demonstrates that 14 out of 61 communities (23%) passed the neutrality test, a percentage significantly higher than the previous reported neutrality rate of 1% in human microbiome (Li &amp; Ma 2016, Scientific Reports). This suggests that, while the niche selection may play a predominant role in the assembly and diversity maintenance in oral microbiome, the effect of neutral dynamics may not be ignored. However, no statistically significant differences in the neutrality passing rates were detected between the periodontitis and healthy treatments with Fisher's exact probability test and multiple testing corrections, suggesting that the mechanism of community assembly is robust against disturbances such as periodontitis. In addition, our study confirmed previous finding that periodontitis patients exhibited higher biodiversity. These findings suggest that while periodontitis may significantly change the community composition measured by diversity (i.e., the exhibition or 'phenotype' of community assembly), it does not seem to cause the 'mutation' of the 'genotype" (mechanism) of community assembly. We argue that the 'phenotypic' changes explain the observed link (not necessarily causal) between periodontitis and community dysbiosis, which is certainly worthy of further investigation.}, }
@article {pmid28810737, year = {2018}, author = {Cohen, LJ and Han, S and Huang, YH and Brady, SF}, title = {Identification of the Colicin V Bacteriocin Gene Cluster by Functional Screening of a Human Microbiome Metagenomic Library.}, journal = {ACS infectious diseases}, volume = {4}, number = {1}, pages = {27-32}, pmid = {28810737}, issn = {2373-8227}, support = {K08 DK109287/DK/NIDDK NIH HHS/United States ; T32 GM007739/GM/NIGMS NIH HHS/United States ; U01 GM110714/GM/NIGMS NIH HHS/United States ; }, mesh = {Colicins/*genetics ; Gene Library ; Humans ; *Metagenome ; *Metagenomics/methods ; *Microbiota ; *Multigene Family ; Sequence Analysis, DNA ; }, abstract = {The forces that shape human microbial ecology are complex. It is likely that human microbiota, similarly to other microbiomes, use antibiotics as one way to establish an ecological niche. In this study, we use functional metagenomics to identify human microbial gene clusters that encode for antibiotic functions. Screening of a metagenomic library prepared from a healthy patient stool sample led to the identification of a family of clones with inserts that are 99% identical to a region of a virulence plasmid found in avian pathogenic Escherichia coli. Characterization of the metagenomic DNA sequence identified a colicin V biosynthetic cluster as being responsible for the observed antibiotic effect of the metagenomic clone against E. coli. This study presents a scalable method to recover antibiotic gene clusters from humans using functional metagenomics and highlights a strategy to study bacteriocins in the human microbiome which can provide a resource for therapeutic discovery.}, }
@article {pmid28808691, year = {2017}, author = {Yasuda, K and Hsu, T and Gallini, CA and Mclver, LJ and Schwager, E and Shi, A and DuLong, CR and Schwager, RN and Abu-Ali, GS and Franzosa, EA and Garrett, WS and Huttenhower, C and Morgan, XC}, title = {Fluoride Depletes Acidogenic Taxa in Oral but Not Gut Microbial Communities in Mice.}, journal = {mSystems}, volume = {2}, number = {4}, pages = {}, pmid = {28808691}, issn = {2379-5077}, support = {R01 CA154426/CA/NCI NIH HHS/United States ; R01 HG005969/HG/NHGRI NIH HHS/United States ; }, abstract = {Fluoridation of drinking water and dental products prevents dental caries primarily by inhibiting energy harvest in oral cariogenic bacteria (such as Streptococcus mutans and Streptococcus sanguinis), thus leading to their depletion. However, the extent to which oral and gut microbial communities are affected by host fluoride exposure has been underexplored. In this study, we modeled human fluoride exposures to municipal water and dental products by treating mice with low or high levels of fluoride over a 12-week period. We then used 16S rRNA gene amplicon and shotgun metagenomic sequencing to assess fluoride's effects on oral and gut microbiome composition and function. In both the low- and high-fluoride groups, several operational taxonomic units (OTUs) belonging to acidogenic bacterial genera (such as Parabacteroides, Bacteroides, and Bilophila) were depleted in the oral community. In addition, fluoride-associated changes in oral community composition resulted in depletion of gene families involved in central carbon metabolism and energy harvest (2-oxoglutarate ferredoxin oxidoreductase, succinate dehydrogenase, and the glyoxylate cycle). In contrast, fluoride treatment did not induce a significant shift in gut microbial community composition or function in our mouse model, possibly due to absorption in the upper gastrointestinal tract. Fluoride-associated perturbations thus appeared to have a selective effect on the composition of the oral but not gut microbial community in mice. Future studies will be necessary to understand possible implications of fluoride exposure for the human microbiome. IMPORTANCE Fluoride has been added to drinking water and dental products since the 1950s. The beneficial effects of fluoride on oral health are due to its ability to inhibit the growth of bacteria that cause dental caries. Despite widespread human consumption of fluoride, there have been only two studies of humans that considered the effect of fluoride on human-associated microbial communities, which are increasingly understood to play important roles in health and disease. Notably, neither of these studies included a true cross-sectional control lacking fluoride exposure, as study subjects continued baseline fluoride treatment in their daily dental hygiene routines. To our knowledge, this work (in mice) is the first controlled study to assess the independent effects of fluoride exposure on the oral and gut microbial communities. Investigating how fluoride interacts with host-associated microbial communities in this controlled setting represents an effort toward understanding how common environmental exposures may potentially influence health.}, }
@article {pmid28800826, year = {2017}, author = {Siroli, L and Patrignani, F and Serrazanetti, DI and Vernocchi, P and Del Chierico, F and Russo, A and Torriani, S and Putignani, L and Gardini, F and Lanciotti, R}, title = {Effect of thyme essential oil and Lactococcus lactis CBM21 on the microbiota composition and quality of minimally processed lamb's lettuce.}, journal = {Food microbiology}, volume = {68}, number = {}, pages = {61-70}, doi = {10.1016/j.fm.2017.06.017}, pmid = {28800826}, issn = {1095-9998}, mesh = {Bacteria/classification/*drug effects/growth &amp; development/isolation &amp; purification ; Biodiversity ; Food Contamination/prevention &amp; control ; Lactococcus lactis/*physiology ; Lactuca/*microbiology ; Oils, Volatile/isolation &amp; purification/*pharmacology ; Plant Extracts/isolation &amp; purification/*pharmacology ; Thymus Plant/*chemistry ; Vegetables/*microbiology ; }, abstract = {The main aim of this work was to evaluate, at pilot scale in an industrial environment, the effects of the biocontrol agent Lactococcus lactis CBM21 and thyme essential oil compared to chlorine, used in the washing step of fresh-cut lamb's lettuce, on the microbiota and its changes in relation to the time of storage. The modification of the microbial population was studied through pyrosequencing in addition to the traditional plate counts. In addition, the volatile molecule and sensory profiles were evaluated during the storage. The results showed no significant differences in terms of total aerobic mesophilic cell loads in relation to the washing solution adopted. However, the pyrosequencing data permitted to identify the genera and species able to dominate the spoilage associations over storage in relation to the treatment applied. Also, the analyses of the volatile molecule profiles of the samples during storage allowed the identification of specific molecules as markers of the spoilage for each different treatment. The sensory analyses after 3 and 5 days of storage showed the preference of the panelists for samples washed with the combination thyme EO and the biocontrol agent. These samples were preferred for attributes such as flavor, acceptability and overall quality. These results highlighted the effect of the innovative washing solutions on the quality of lettuce through the shift of microbiota towards genera and species with lower potential in decreasing the sensory properties of the product.}, }
@article {pmid28793934, year = {2017}, author = {Caparrós-Martín, JA and Lareu, RR and Ramsay, JP and Peplies, J and Reen, FJ and Headlam, HA and Ward, NC and Croft, KD and Newsholme, P and Hughes, JD and O'Gara, F}, title = {Statin therapy causes gut dysbiosis in mice through a PXR-dependent mechanism.}, journal = {Microbiome}, volume = {5}, number = {1}, pages = {95}, pmid = {28793934}, issn = {2049-2618}, mesh = {Animals ; Bile Acids and Salts/analysis ; Blood Glucose/analysis ; Butyrates/analysis ; Diabetes Mellitus, Type 2/etiology ; Dysbiosis/*etiology/physiopathology ; Gastrointestinal Microbiome/*drug effects ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/*adverse effects/therapeutic use ; Intestines/*drug effects/microbiology/physiopathology ; Lipid Metabolism/genetics ; Male ; Mice ; Mice, Knockout ; Pregnane X Receptor ; Receptors, Steroid/*genetics ; Weight Gain/drug effects ; }, abstract = {BACKGROUND: Statins are a class of therapeutics used to regulate serum cholesterol and reduce the risk of heart disease. Although statins are highly effective in removing cholesterol from the blood, their consumption has been linked to potential adverse effects in some individuals. The most common events associated with statin intolerance are myopathy and increased risk of developing type 2 diabetes mellitus. However, the pathological mechanism through which statins cause these adverse effects is not well understood.<br><br>RESULTS: Using a murine model, we describe for the first time profound changes in the microbial composition of the gut following statin treatment. This remodelling affected the diversity and metabolic profile of the gut microbiota and was associated with reduced production of butyrate. Statins altered both the size and composition of the bile acid pool in the intestine, tentatively explaining the observed gut dysbiosis. As also observed in patients, statin-treated mice trended towards increased fasting blood glucose levels and weight gain compared to controls. Statin treatment affected the hepatic expression of genes involved in lipid and glucose metabolism. Using gene knockout mice, we demonstrated that the observed effects were mediated through pregnane X receptor (PXR).<br><br>CONCLUSION: This study demonstrates that statin therapy drives a profound remodelling of the gut microbiota, hepatic gene deregulation and metabolic alterations in mice through a PXR-dependent mechanism. Since the demonstrated importance of the intestinal microbial community in host health, this work provides new perspectives to help prevent the statin-associated unintended metabolic effects.}, }
@article {pmid28785422, year = {2017}, author = {Gundogdu, A and Nalbantoglu, U}, title = {Human genome-microbiome interaction: metagenomics frontiers for the aetiopathology of autoimmune diseases.}, journal = {Microbial genomics}, volume = {3}, number = {4}, pages = {e000112}, pmid = {28785422}, issn = {2057-5858}, mesh = {Autoimmune Diseases/*genetics/*microbiology ; Autoimmunity/*genetics ; Genetic Variation ; Genome, Human ; Host Microbial Interactions/*genetics ; Humans ; Machine Learning ; Metagenomics ; Microbiota/*genetics ; Systems Biology ; }, abstract = {A short while ago, the human genome and microbiome were analysed simultaneously for the first time as a multi-omic approach. The analyses of heterogeneous population cohorts showed that microbiome components were associated with human genome variations. In-depth analysis of these results reveals that the majority of those relationships are between immune pathways and autoimmune disease-associated microbiome components. Thus, it can be hypothesized that autoimmunity may be associated with homeostatic disequilibrium of the human-microbiome interactome. Further analysis of human genome-human microbiome relationships in disease contexts with tailored systems biology approaches may yield insights into disease pathogenesis and prognosis.}, }
@article {pmid28777382, year = {2017}, author = {Adam, PS and Borrel, G and Brochier-Armanet, C and Gribaldo, S}, title = {The growing tree of Archaea: new perspectives on their diversity, evolution and ecology.}, journal = {The ISME journal}, volume = {11}, number = {11}, pages = {2407-2425}, pmid = {28777382}, issn = {1751-7370}, mesh = {Archaea/*classification/genetics/*isolation &amp; purification ; *Biodiversity ; Ecology ; Genome, Archaeal ; Phylogeny ; }, abstract = {The Archaea occupy a key position in the Tree of Life, and are a major fraction of microbial diversity. Abundant in soils, ocean sediments and the water column, they have crucial roles in processes mediating global carbon and nutrient fluxes. Moreover, they represent an important component of the human microbiome, where their role in health and disease is still unclear. The development of culture-independent sequencing techniques has provided unprecedented access to genomic data from a large number of so far inaccessible archaeal lineages. This is revolutionizing our view of the diversity and metabolic potential of the Archaea in a wide variety of environments, an important step toward understanding their ecological role. The archaeal tree is being rapidly filled up with new branches constituting phyla, classes and orders, generating novel challenges for high-rank systematics, and providing key information for dissecting the origin of this domain, the evolutionary trajectories that have shaped its current diversity, and its relationships with Bacteria and Eukarya. The present picture is that of a huge diversity of the Archaea, which we are only starting to explore.}, }
@article {pmid28771951, year = {2017}, author = {Wong, WF and Santiago, M}, title = {Microbial approaches for targeting antibiotic-resistant bacteria.}, journal = {Microbial biotechnology}, volume = {10}, number = {5}, pages = {1047-1053}, pmid = {28771951}, issn = {1751-7915}, mesh = {Animals ; Anti-Bacterial Agents/*pharmacology ; Bacteria/*drug effects/genetics/metabolism ; Bacterial Infections/*microbiology/therapy ; *Drug Resistance, Bacterial ; Humans ; Microbiota ; }, abstract = {Antibiotic resistant bacterial infections are a global public health challenge that has been increasing in severity and scope for the last few decades. Without creative solutions to this problem, treatment of injuries and infections will become progressively more challenging. A better understanding of the human microbiome has led to a new appreciation for the role commensal microbes play in protecting us from pathogens, especially in the gut. Antibiotics lead to disruption of the gut microbial ecosystem, enabling colonization by antibiotic resistant bacterial pathogens. Many different lines of research have identified specific bacterial taxa and mechanisms that play a role in colonization resistance, and these lines of research may one day lead to microbial therapeutics targeting antibiotic resistant bacteria. Here, we discuss a few of these strategies and the challenges they will need to overcome in order to become an effective therapeutic.}, }
@article {pmid28771841, year = {2017}, author = {Boost, M and Cho, P and Wang, Z}, title = {Disturbing the balance: effect of contact lens use on the ocular proteome and microbiome.}, journal = {Clinical &amp; experimental optometry}, volume = {100}, number = {5}, pages = {459-472}, doi = {10.1111/cxo.12582}, pmid = {28771841}, issn = {1444-0938}, mesh = {Contact Lenses/*statistics &amp; numerical data ; Cornea/*metabolism ; Humans ; Microbiota/*physiology ; Proteome/*metabolism ; Proteostasis/*physiology ; Refractive Errors/therapy ; Tears/*metabolism ; Vision Disorders/therapy ; }, abstract = {Contact lens wear is a popular, convenient and effective method for vision correction. In recent years, contact lens practice has expanded to include new paradigms, including orthokeratology; however, their use is not entirely without risk, as the incidence of infection has consistently been reported to be higher in contact lens wearers. The explanations for this increased susceptibility have largely focused on physical damage, especially to the cornea, due to a combination of hypoxia, mechanical trauma, deposits and solution cytotoxicity, as well as poor compliance with care routines leading to introduction of pathogens into the ocular environment. However, in recent years, with the increasing availability and reduced cost of molecular techniques, the ocular environment has received greater attention with in-depth studies of proteins and other components. Numerous proteins were found to be present in the tears and their functions and interactions indicate that the tears are far more complex than formerly presumed. In addition, the concept of a sterile or limited microbial population on the ocular surface has been challenged by analysis of the microbiome. Ocular microbiome was not considered as one of the key sites for the Human Microbiome Project, as it was thought to be limited compared to other body sites. This was proven to be fallacious, as a wide variety of micro-organisms were identified in the analyses of human tears. Thus, the ocular environment is now recognised to be more complicated and interference with this ecological balance may lead to adverse effects. The use of contact lenses clearly changes the situation at the ocular surface, which may result in consequences which disturb the balance in the healthy eye.}, }
@article {pmid28769875, year = {2017}, author = {Vecchio-Pagan, B and Bewick, S and Mainali, K and Karig, DK and Fagan, WF}, title = {A Stoichioproteomic Analysis of Samples from the Human Microbiome Project.}, journal = {Frontiers in microbiology}, volume = {8}, number = {}, pages = {1119}, pmid = {28769875}, issn = {1664-302X}, abstract = {Ecological stoichiometry (ES) uses organism-specific elemental content to explain differences in species life histories, species interactions, community organization, environmental constraints and even ecosystem function. Although ES has been successfully applied to a range of different organisms, most emphasis on microbial ecological stoichiometry focuses on lake, ocean, and soil communities. With the recent advances in human microbiome research, however, large amounts of data are being generated that describe differences in community composition across body sites and individuals. We suggest that ES may provide a framework for beginning to understand the structure, organization, and function of human microbial communities, including why certain organisms exist at certain locations, and how they interact with both the other microbes in their environment and their human host. As a first step, we undertake a stoichioproteomic analysis of microbial communities from different body sites. Specifically, we compare and contrast the elemental composition of microbial protein samples using annotated sequencing data from 690 gut, vaginal, oral, nares, and skin samples currently available through the Human Microbiome Project. Our results suggest significant differences in both the median and variance of the carbon, oxygen, nitrogen, and sulfur contents of microbial protein samples from different locations. For example, whereas proteins from vaginal sites are high in carbon, proteins from skin and nasal sites are high in nitrogen and oxygen. Meanwhile, proteins from stool (the gut) are particularly high in sulfur content. We interpret these differences in terms of the local environments at different human body sites, including atmospheric exposure and food intake rates.}, }
@article {pmid28767318, year = {2018}, author = {Malan-Muller, S and Valles-Colomer, M and Raes, J and Lowry, CA and Seedat, S and Hemmings, SMJ}, title = {The Gut Microbiome and Mental Health: Implications for Anxiety- and Trauma-Related Disorders.}, journal = {Omics : a journal of integrative biology}, volume = {22}, number = {2}, pages = {90-107}, doi = {10.1089/omi.2017.0077}, pmid = {28767318}, issn = {1557-8100}, mesh = {Animals ; Anxiety/genetics/*microbiology ; Gastrointestinal Microbiome/genetics/*physiology ; Humans ; Mental Disorders/genetics/*microbiology ; Mental Health ; RNA, Ribosomal, 16S/genetics ; Trauma and Stressor Related Disorders/genetics/*microbiology ; }, abstract = {Biological psychiatry research has long focused on the brain in elucidating the neurobiological mechanisms of anxiety- and trauma-related disorders. This review challenges this assumption and suggests that the gut microbiome and its interactome also deserve attention to understand brain disorders and develop innovative treatments and diagnostics in the 21st century. The recent, in-depth characterization of the human microbiome spurred a paradigm shift in human health and disease. Animal models strongly suggest a role for the gut microbiome in anxiety- and trauma-related disorders. The microbiota-gut-brain (MGB) axis sits at the epicenter of this new approach to mental health. The microbiome plays an important role in the programming of the hypothalamic-pituitary-adrenal (HPA) axis early in life, and stress reactivity over the life span. In this review, we highlight emerging findings of microbiome research in psychiatric disorders, focusing on anxiety- and trauma-related disorders specifically, and discuss the gut microbiome as a potential therapeutic target. 16S rRNA sequencing has enabled researchers to investigate and compare microbial composition between individuals. The functional microbiome can be studied using methods involving metagenomics, metatranscriptomics, metaproteomics, and metabolomics, as discussed in the present review. Other factors that shape the gut microbiome should be considered to obtain a holistic view of the factors at play in the complex interactome linked to the MGB. In all, we underscore the importance of microbiome science, and gut microbiota in particular, as emerging critical players in mental illness and maintenance of mental health. This new frontier of biological psychiatry and postgenomic medicine should be embraced by the mental health community as it plays an ever-increasing transformative role in integrative and holistic health research in the next decade.}, }
@article {pmid28766918, year = {2018}, author = {Sherwani, MA and Tufail, S and Muzaffar, AF and Yusuf, N}, title = {The skin microbiome and immune system: Potential target for chemoprevention?.}, journal = {Photodermatology, photoimmunology &amp; photomedicine}, volume = {34}, number = {1}, pages = {25-34}, pmid = {28766918}, issn = {1600-0781}, support = {R01 AR071157/AR/NIAMS NIH HHS/United States ; }, mesh = {Animals ; Gastrointestinal Microbiome ; Humans ; *Microbiota/radiation effects ; Prebiotics ; Probiotics/pharmacology ; Skin/*immunology/*microbiology ; Skin Neoplasms/immunology/*microbiology/*prevention &amp; control ; Ultraviolet Rays ; Virus Diseases/complications ; Vitamin D/analogs &amp; derivatives/metabolism ; }, abstract = {There has been increasing interest in understanding the role of the human microbiome in skin diseases. Microbiome studies are being utilized in skin cancer research in numerous ways. Commensal bacteria are being studied as a potential tool to judge the biggest environmental risk of skin cancer, ultraviolet (UV) radiation. Owing to the recognized link of skin microbes in the process of inflammation, there have been theories linking commensal bacteria to skin cancer. Viral metagenomics has also provided insight into virus linked forms of skin cancers. Speculations can be drawn for skin microbiome that in a manner similar to gut microbiome, they can be involved in chemoprevention of skin cancer. Nonetheless, there are definitely huge gaps in our knowledge of the relationship of microbiome and skin cancers, especially in relation to chemoprevention. The utilization of microbiome in skin cancer research seems to be a promising field and may help yield novel skin cancer prevention and treatment options. This review focuses on recent utilization of the microbiome in skin cancer research, and it explores the potential of utilizing the microbiome in prevention, earlier diagnosis, and treatment of skin cancers.}, }
@article {pmid28761935, year = {2017}, author = {Ross, AA and Doxey, AC and Neufeld, JD}, title = {The Skin Microbiome of Cohabiting Couples.}, journal = {mSystems}, volume = {2}, number = {4}, pages = {}, pmid = {28761935}, issn = {2379-5077}, abstract = {Distinct microbial communities inhabit individuals as part of the human skin microbiome and are continually shed to the surrounding environment. Microbial communities from 17 skin sites of 10 sexually active cohabiting couples (20 individuals) were sampled to test whether cohabitation impacts an individual's skin microbiome, leading to shared skin microbiota among partner pairs. Amplified 16S rRNA genes of bacteria and archaea from a total of 340 skin swabs were analyzed by high-throughput sequencing, and the results demonstrated that cohabitation was significantly associated with microbial community composition, although this association was greatly exceeded by characteristics of body location and individuality. Random forest modeling demonstrated that the partners could be predicted 86% of the time (P < 0.001) based on their skin microbiome profiles, which was always greater than combinations of incorrectly matched partners. Cohabiting couples had the most similar overall microbial skin communities on their feet, according to Bray-Curtis distances. In contrast, thigh microbial communities were strongly associated with biological sex rather than cohabiting partner. Additional factors that were associated with the skin microbiome of specific body locations included the use of skin care products, pet ownership, allergies, and alcohol consumption. These baseline data identified links between the skin microbiome and daily interactions among cohabiting individuals, adding to known factors that shape the human microbiome and, by extension, its relation to human health. IMPORTANCE Our work characterizes the influence of cohabitation as a factor influencing the composition of the skin microbiome. Although the body site and sampled individual were stronger influences than other factors collected as metadata in this study, we show that modeling of detected microbial taxa can help with correct identifications of cohabiting partners based on skin microbiome profiles using machine learning approaches. These results show that a cohabiting partner can significantly influence our microbiota. Follow-up studies will be important for investigating the implications of shared microbiota on dermatological health and the contributions of cohabiting parents to the microbiome profiles of their infants.}, }
@article {pmid28761934, year = {2017}, author = {Edlund, A and Garg, N and Mohimani, H and Gurevich, A and He, X and Shi, W and Dorrestein, PC and McLean, JS}, title = {Metabolic Fingerprints from the Human Oral Microbiome Reveal a Vast Knowledge Gap of Secreted Small Peptidic Molecules.}, journal = {mSystems}, volume = {2}, number = {4}, pages = {}, pmid = {28761934}, issn = {2379-5077}, support = {R01 DE023810/DE/NIDCR NIH HHS/United States ; R01 DE026186/DE/NIDCR NIH HHS/United States ; K99 DE024543/DE/NIDCR NIH HHS/United States ; R00 DE024543/DE/NIDCR NIH HHS/United States ; P41 GM103484/GM/NIGMS NIH HHS/United States ; R01 DE020102/DE/NIDCR NIH HHS/United States ; R01 GM095373/GM/NIGMS NIH HHS/United States ; }, abstract = {Recent research indicates that the human microbiota play key roles in maintaining health by providing essential nutrients, providing immune education, and preventing pathogen expansion. Processes underlying the transition from a healthy human microbiome to a disease-associated microbiome are poorly understood, partially because of the potential influences from a wide diversity of bacterium-derived compounds that are illy defined. Here, we present the analysis of peptidic small molecules (SMs) secreted from bacteria and viewed from a temporal perspective. Through comparative analysis of mass spectral profiles from a collection of cultured oral isolates and an established in vitro multispecies oral community, we found that the production of SMs both delineates a temporal expression pattern and allows discrimination between bacterial isolates at the species level. Importantly, the majority of the identified molecules were of unknown identity, and only ~2.2% could be annotated and classified. The catalogue of bacterially produced SMs we obtained in this study reveals an undiscovered molecular world for which compound isolation and ecosystem testing will facilitate a better understanding of their roles in human health and disease. IMPORTANCE Metabolomics is the ultimate tool for studies of microbial functions under any specific set of environmental conditions (D. S. Wishart, Nat Rev Drug Discov 45:473-484, 2016, https://doi.org/10.1038/nrd.2016.32). This is a great advance over studying genes alone, which only inform about metabolic potential. Approximately 25,000 compounds have been chemically characterized thus far; however, the richness of metabolites such as SMs has been estimated to be as high as 1 × 10[30] in the biosphere (K. Garber, Nat Biotechnol 33:228-231, 2015, https://doi.org/10.1038/nbt.3161). Our classical, one-at-a-time activity-guided approach to compound identification continues to find the same known compounds and is also incredibly tedious, which represents a major bottleneck for global SM identification. These challenges have prompted new developments of databases and analysis tools that provide putative classifications of SMs by mass spectral alignments to already characterized tandem mass spectrometry spectra and databases containing structural information (e.g., PubChem and AntiMarin). In this study, we assessed secreted peptidic SMs (PSMs) from 27 oral bacterial isolates and a complex oral in vitro biofilm community of >100 species by using the Global Natural Products Social molecular Networking and the DEREPLICATOR infrastructures, which are methodologies that allow automated and putative annotation of PSMs. These approaches enabled the identification of an untapped resource of PSMs from oral bacteria showing species-unique patterns of secretion with putative matches to known bioactive compounds.}, }
@article {pmid28760934, year = {2017}, author = {Spinler, JK and Auchtung, J and Brown, A and Boonma, P and Oezguen, N and Ross, CL and Luna, RA and Runge, J and Versalovic, J and Peniche, A and Dann, SM and Britton, RA and Haag, A and Savidge, TC}, title = {Next-Generation Probiotics Targeting Clostridium difficile through Precursor-Directed Antimicrobial Biosynthesis.}, journal = {Infection and immunity}, volume = {85}, number = {10}, pages = {}, pmid = {28760934}, issn = {1098-5522}, support = {U01 AI124290/AI/NIAID NIH HHS/United States ; U19 AI090872/AI/NIAID NIH HHS/United States ; UL1 TR000071/TR/NCATS NIH HHS/United States ; P30 DK056338/DK/NIDDK NIH HHS/United States ; R21 DK096323/DK/NIDDK NIH HHS/United States ; }, mesh = {Anti-Bacterial Agents/*biosynthesis/pharmacology/therapeutic use ; Bacterial Proteins/genetics ; Clostridioides difficile/drug effects/*growth &amp; development ; Clostridium Infections/immunology/*prevention &amp; control/therapy ; Drug Discovery/methods ; Drug Resistance, Bacterial ; Feces/microbiology ; Fermentation ; Gastrointestinal Microbiome ; Glyceraldehyde/*analogs &amp; derivatives/metabolism/pharmacology/therapeutic use ; Glycerol/*administration &amp; dosage/immunology/metabolism ; Humans ; Limosilactobacillus reuteri/*metabolism ; Metabolomics ; *Probiotics ; Propane/*metabolism/pharmacology/therapeutic use ; Vancomycin/pharmacology ; }, abstract = {Integration of antibiotic and probiotic therapy has the potential to lessen the public health burden of antimicrobial-associated diseases. Clostridium difficile infection (CDI) represents an important example where the rational design of next-generation probiotics is being actively pursued to prevent disease recurrence. Because intrinsic resistance to clinically relevant antibiotics used to treat CDI (vancomycin, metronidazole, and fidaxomicin) is a desired trait in such probiotic species, we screened several bacteria and identified Lactobacillus reuteri to be a promising candidate for adjunct therapy. Human-derived L. reuteri bacteria convert glycerol to the broad-spectrum antimicrobial compound reuterin. When supplemented with glycerol, strains carrying the pocR gene locus were potent reuterin producers, with L. reuteri 17938 inhibiting C. difficile growth at a level on par with the level of growth inhibition by vancomycin. Targeted pocR mutations and complementation studies identified reuterin to be the precursor-induced antimicrobial agent. Pathophysiological relevance was demonstrated when the codelivery of L. reuteri with glycerol was effective against C. difficile colonization in complex human fecal microbial communities, whereas treatment with either glycerol or L. reuteri alone was ineffective. A global unbiased microbiome and metabolomics analysis independently confirmed that glycerol precursor delivery with L. reuteri elicited changes in the composition and function of the human microbial community that preferentially targets C. difficile outgrowth and toxicity, a finding consistent with glycerol fermentation and reuterin production. Antimicrobial resistance has thus been successfully exploited in the natural design of human microbiome evasion of C. difficile, and this method may provide a prototypic precursor-directed probiotic approach. Antibiotic resistance and substrate bioavailability may therefore represent critical new determinants of probiotic efficacy in clinical trials.}, }
@article {pmid28759253, year = {2017}, author = {Scriba, TJ and Carpenter, C and Pro, SC and Sidney, J and Musvosvi, M and Rozot, V and Seumois, G and Rosales, SL and Vijayanand, P and Goletti, D and Makgotlho, E and Hanekom, W and Hatherill, M and Peters, B and Sette, A and Arlehamn, CSL}, title = {Differential Recognition of Mycobacterium tuberculosis-Specific Epitopes as a Function of Tuberculosis Disease History.}, journal = {American journal of respiratory and critical care medicine}, volume = {196}, number = {6}, pages = {772-781}, pmid = {28759253}, issn = {1535-4970}, support = {HHSN272200900044C/AI/NIAID NIH HHS/United States ; U19 AI111211/AI/NIAID NIH HHS/United States ; U19 AI118626/AI/NIAID NIH HHS/United States ; }, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Antigens, Bacterial/*blood ; Child ; Child, Preschool ; Cohort Studies ; Enzyme-Linked Immunospot Assay ; Epitopes, T-Lymphocyte/*blood ; Female ; Humans ; Infant ; Male ; Middle Aged ; Mycobacterium tuberculosis/*genetics/*immunology ; Tuberculosis/*immunology ; Young Adult ; }, abstract = {RATIONALE: Individuals with a history of tuberculosis (TB) disease are at elevated risk of disease recurrence. The underlying cause is not known, but one explanation is that previous disease results in less-effective immunity against Mycobacterium tuberculosis (Mtb).<br><br>OBJECTIVES: We hypothesized that the repertoire of Mtb-derived epitopes recognized by T cells from individuals with latent Mtb infection differs as a function of previous diagnosis of active TB disease.<br><br>METHODS: T-cell responses to peptide pools in samples collected from an adult screening and an adolescent validation cohort were measured by IFN-&#x3b3; enzyme-linked immunospot assay or intracellular cytokine staining.<br><br>MEASUREMENTS AND MAIN RESULTS: We identified a set of "type 2" T-cell epitopes that were recognized at 10-fold-lower levels in Mtb-infected individuals with a history of TB disease less than 6 years ago than in those without previous TB. By contrast, "type 1" epitopes were recognized equally well in individuals with or without previous TB. The differential epitope recognition was not due to differences in HLA class II binding, memory phenotypes, or gene expression in the responding T cells. Instead, "TB disease history-sensitive" type 2 epitopes were significantly (P&#x2009;<&#x2009;0.0001) more homologous to sequences from bacteria found in the human microbiome than type 1 epitopes.<br><br>CONCLUSIONS: Preferential loss of T-cell reactivity to Mtb epitopes that are homologous to bacteria in the microbiome in persons with previous TB disease may reflect long-term effects of antibiotic TB treatment on the microbiome.}, }
@article {pmid28754707, year = {2017}, author = {Peixoto, RJM and Alves, ES and Wang, M and Ferreira, RBR and Granato, A and Han, J and Gill, H and Jacobson, K and Lobo, LA and Domingues, RMCP and Borchers, CH and Davies, JE and Finlay, BB and Antunes, LCM}, title = {Repression of Salmonella Host Cell Invasion by Aromatic Small Molecules from the Human Fecal Metabolome.}, journal = {Applied and environmental microbiology}, volume = {83}, number = {19}, pages = {}, pmid = {28754707}, issn = {1098-5336}, abstract = {The human microbiome is a collection of microorganisms that inhabit every surface of the body that is exposed to the environment, generally coexisting peacefully with their host. These microbes have important functions, such as producing vitamins, aiding in maturation of the immune system, and protecting against pathogens. We have previously shown that a small-molecule extract from the human fecal microbiome has a strong repressive effect on Salmonella enterica serovar Typhimurium host cell invasion by modulating the expression of genes involved in this process. Here, we describe the characterization of this biological activity. Using a series of purification methods, we obtained fractions with biological activity and characterized them by mass spectrometry. These experiments revealed an abundance of aromatic compounds in the bioactive fraction. Selected compounds were obtained from commercial sources and tested with respect to their ability to repress the expression of hilA, the gene encoding the master regulator of invasion genes in Salmonella We found that the aromatic compound 3,4-dimethylbenzoic acid acts as a strong inhibitor of hilA expression and of invasion of cultured host cells by Salmonella Future studies should reveal the molecular details of this phenomenon, such as the signaling cascades involved in sensing this bioactive molecule.IMPORTANCE Microbes constantly sense and adapt to their environment. Often, this is achieved through the production and sensing of small extracellular molecules. The human body is colonized by complex communities of microbes, and, given their biological and chemical diversity, these ecosystems represent a platform where the production and sensing of molecules occur. In previous work, we showed that small molecules produced by microbes from the human gut can significantly impair the virulence of the enteric pathogen Salmonella enterica Here, we describe a specific compound from the human gut that produces this same effect. The results from this work not only shed light on an important biological phenomenon occurring in our bodies but also may represent an opportunity to develop drugs that can target these small-molecule interactions to protect us from enteric infections and other diseases.}, }
@article {pmid28750103, year = {2017}, author = {Van Leuvenhaege, C and Vandelannoote, K and Affolabi, D and Portaels, F and Sopoh, G and de Jong, BC and Eddyani, M and Meehan, CJ}, title = {Bacterial diversity in Buruli ulcer skin lesions: Challenges in the clinical microbiome analysis of a skin disease.}, journal = {PloS one}, volume = {12}, number = {7}, pages = {e0181994}, pmid = {28750103}, issn = {1932-6203}, mesh = {Adolescent ; Adult ; Aged ; Buruli Ulcer/*microbiology ; Case-Control Studies ; Child ; Humans ; *Microbiota/drug effects ; Middle Aged ; Mycobacterium ulcerans/classification ; Oxygen/pharmacology ; Phylogeny ; Principal Component Analysis ; Skin/*microbiology/*pathology ; Staining and Labeling ; Young Adult ; }, abstract = {BACKGROUND: Buruli ulcer (BU) is an infectious disease caused by Mycobacterium ulcerans and considered the third most prevalent mycobacterial disease in humans. Secondary bacterial infections in open BU lesions are the main cause of pain, delayed healing and systemic illness, resulting in prolonged hospital stay. Thus, understanding the diversity of bacteria, termed the microbiome, in these open lesions is important for proper treatment. However, adequately studying the human microbiome in a clinical setting can prove difficult when investigating a neglected tropical skin disease due to its rarity and the setting.<br><br>Using 16S rRNA sequencing, we determined the microbial composition of 5 BU lesions, 3 non-BU lesions and 3 healthy skin samples. Although no significant differences in diversity were found between BU and non-BU lesions, the former were characterized by an increase of Bacteroidetes compared to the non-BU wounds and the BU lesions also contained significantly more obligate anaerobes. With this molecular-based study, we were also able to detect bacteria that were missed by culture-based methods in previous BU studies.<br><br>CONCLUSIONS/SIGNIFICANCE: Our study suggests that BU may lead to changes in the skin bacterial community within the lesions. However, in order to determine if such changes hold true across all BU cases and are either a cause or consequence of a specific wound environment, further microbiome studies are necessary. Such skin microbiome analysis requires large sample sizes and lesions from the same body site in many patients, both of which can be difficult for a rare disease. Our study proposes a pipeline for such studies and highlights several drawbacks that must be considered if microbiome analysis is to be utilized for neglected tropical diseases.}, }
@article {pmid28745328, year = {2018}, author = {Ganesh, BP and Hall, A and Ayyaswamy, S and Nelson, JW and Fultz, R and Major, A and Haag, A and Esparza, M and Lugo, M and Venable, S and Whary, M and Fox, JG and Versalovic, J}, title = {Diacylglycerol kinase synthesized by commensal Lactobacillus reuteri diminishes protein kinase C phosphorylation and histamine-mediated signaling in the mammalian intestinal epithelium.}, journal = {Mucosal immunology}, volume = {11}, number = {2}, pages = {380-393}, pmid = {28745328}, issn = {1935-3456}, support = {U01 CA170930/CA/NCI NIH HHS/United States ; R01 OD011141/OD/NIH HHS/United States ; UH3 DK083990/DK/NIDDK NIH HHS/United States ; P30 ES002109/ES/NIEHS NIH HHS/United States ; P30 DK056338/DK/NIDDK NIH HHS/United States ; T32 OD010978/OD/NIH HHS/United States ; R01 AT004326/AT/NCCIH NIH HHS/United States ; }, mesh = {Animals ; Bacterial Proteins/genetics/*metabolism ; Cytokines/metabolism ; Diacylglycerol Kinase/genetics/*metabolism ; Histamine/immunology ; Humans ; Inflammation Mediators/metabolism ; Intestinal Mucosa/*immunology/microbiology ; Limosilactobacillus reuteri/*metabolism/physiology ; Mice ; Mice, Inbred BALB C ; Microbiota ; Mutation/genetics ; Phosphorylation ; Protein Kinase C/*metabolism ; Receptors, Histamine H1/metabolism ; Receptors, Histamine H2/*metabolism ; Signal Transduction ; }, abstract = {Lactobacillus reuteri 6475 (Lr) of the human microbiome synthesizes histamine and can suppress inflammation via type 2 histamine receptor (H2R) activation in the mammalian intestine. Gut microbes such as Lr promote H2R signaling and may suppress H1R proinflammatory signaling pathways in parallel by unknown mechanisms. In this study, we identified a soluble bacterial enzyme known as diacylglycerol kinase (Dgk) from Lr that is secreted into the extracellular milieu and presumably into the intestinal lumen. DgK diminishes diacylglycerol (DAG) quantities in mammalian cells by promoting its metabolic conversion and causing reduced protein kinase C phosphorylation (pPKC) as a net effect in mammalian cells. We demonstrated that histamine synthesized by gut microbes (Lr) activates both mammalian H1R and H2R, but Lr-derived Dgk suppresses the H1R signaling pathway. Phospho-PKC and IκBα were diminished within the intestinal epithelium of mice and humans treated by wild-type (WT) Lr, but pPKC and IκBα were not decreased in treatment with ΔdgkA Lr. Mucosal IL-6 and systemic interleukin (IL)-1α, eotaxin, and granulocyte colony-stimulating factor (G-CSF) were suppressed in WT Lr, but not in ΔdgkA Lr colonized mice. Collectively, the commensal microbe Lr may act as a "microbial antihistamine" by suppressing intestinal H1R-mediated proinflammatory responses via diminished pPKC-mediated mammalian cell signaling.}, }
@article {pmid28742161, year = {2017}, author = {Rendueles, O and Garcia-Garcerà, M and Néron, B and Touchon, M and Rocha, EPC}, title = {Abundance and co-occurrence of extracellular capsules increase environmental breadth: Implications for the emergence of pathogens.}, journal = {PLoS pathogens}, volume = {13}, number = {7}, pages = {e1006525}, pmid = {28742161}, issn = {1553-7374}, support = {281605/ERC_/European Research Council/International ; }, mesh = {Bacteria/classification/genetics/*metabolism/pathogenicity ; Bacterial Capsules/*metabolism ; Bacterial Infections/*microbiology ; Bacterial Proteins/genetics/metabolism ; Genome, Bacterial ; Humans ; Phylogeny ; Virulence ; }, abstract = {Extracellular capsules constitute the outermost layer of many bacteria, are major virulence factors, and affect antimicrobial therapies. They have been used as epidemiological markers and recently became vaccination targets. Despite the efforts to biochemically serotype capsules in a few model pathogens, little is known of their taxonomic and environmental distribution. We developed, validated, and made available a computational tool, CapsuleFinder, to identify capsules in genomes. The analysis of over 2500 prokaryotic genomes, accessible in a database, revealed that ca. 50% of them-including Archaea-encode a capsule. The Wzx/Wzy-dependent capsular group was by far the most abundant. Surprisingly, a fifth of the genomes encode more than one capsule system-often from different groups-and their non-random co-occurrence suggests the existence of negative and positive epistatic interactions. To understand the role of multiple capsules, we queried more than 6700 metagenomes for the presence of species encoding capsules and showed that their distribution varied between environmental categories and, within the human microbiome, between body locations. Species encoding capsules, and especially those encoding multiple capsules, had larger environmental breadths than the other species. Accordingly, capsules were more frequent in environmental bacteria than in pathogens and, within the latter, they were more frequent among facultative pathogens. Nevertheless, capsules were frequent in clinical samples, and were usually associated with fast-growing bacteria with high infectious doses. Our results suggest that capsules increase the environmental range of bacteria and make them more resilient to environmental perturbations. Capsules might allow opportunistic pathogens to profit from empty ecological niches or environmental perturbations, such as those resulting from antibiotic therapy, to colonize the host. Capsule-associated virulence might thus be a by-product of environmental adaptation. Understanding the role of capsules in natural environments might enlighten their function in pathogenesis.}, }
@article {pmid28737021, year = {2017}, author = {Brüssow, H}, title = {Infection therapy: the problem of drug resistance - and possible solutions.}, journal = {Microbial biotechnology}, volume = {10}, number = {5}, pages = {1041-1046}, pmid = {28737021}, issn = {1751-7915}, mesh = {Animals ; Anti-Bacterial Agents/administration &amp; dosage ; Bacteria/*drug effects/genetics/metabolism/virology ; Bacterial Infections/drug therapy/microbiology/*therapy ; Bacteriophages/physiology ; Biological Therapy ; Drug Resistance, Bacterial ; Humans ; Probiotics/administration &amp; dosage ; }, abstract = {The rising antibiotic resistance in major bacterial pathogens together with the breakdown of the antibiotic discovery platform creates a critical situation for infection therapy. Recent developments reviving new antibiotic discovery from defining chemical rules for membrane-passing compounds to isolation chips for soil bacteria and exploring the human microbiome for antibiotic-producing bacteria are discussed. The potential of bacteriocins, tailocins, phage lysins, phages, probiotics and commensal blends as alternatives to antibiotics is evaluated.}, }
@article {pmid28730144, year = {2017}, author = {Yu, G and Torres, J and Hu, N and Medrano-Guzman, R and Herrera-Goepfert, R and Humphrys, MS and Wang, L and Wang, C and Ding, T and Ravel, J and Taylor, PR and Abnet, CC and Goldstein, AM}, title = {Molecular Characterization of the Human Stomach Microbiota in Gastric Cancer Patients.}, journal = {Frontiers in cellular and infection microbiology}, volume = {7}, number = {}, pages = {302}, pmid = {28730144}, issn = {2235-2988}, mesh = {Adult ; Aged ; Bacteria/classification/genetics/*isolation &amp; purification ; China ; Female ; *Gastrointestinal Microbiome ; Helicobacter pylori/classification/genetics/isolation &amp; purification ; Humans ; Male ; Mexico ; Middle Aged ; Stomach/*microbiology ; Stomach Neoplasms/*microbiology ; Young Adult ; }, abstract = {Helicobacter pylori (Hp) is the primary cause of gastric cancer but we know little of its relative abundance and other microbes in the stomach, especially at the time of gastric cancer diagnosis. Here we characterized the taxonomic and derived functional profiles of gastric microbiota in two different sets of gastric cancer patients, and compared them with microbial profiles in other body sites. Paired non-malignant and tumor tissues were sampled from 160 gastric cancer patients with 80 from China and 80 from Mexico. The 16S rRNA gene V3-V4 region was sequenced using MiSeq platform for taxonomic profiles. PICRUSt was used to predict functional profiles. Human Microbiome Project was used for comparison. We showed that Hp is the most abundant member of gastric microbiota in both Chinese and Mexican samples (51 and 24%, respectively), followed by oral-associated bacteria. Taxonomic (phylum-level) profiles of stomach microbiota resembled oral microbiota, especially when the Helicobacter reads were removed. The functional profiles of stomach microbiota, however, were distinct from those found in other body sites and had higher inter-subject dissimilarity. Gastric microbiota composition did not differ by Hp colonization status or stomach anatomic sites, but did differ between paired non-malignant and tumor tissues in either Chinese or Mexican samples. Our study showed that Hp is the dominant member of the non-malignant gastric tissue microbiota in many gastric cancer patients. Our results provide insights on the gastric microbiota composition and function in gastric cancer patients, which may have important clinical implications.}, }
@article {pmid28728057, year = {2017}, author = {Clarke, TH and Gomez, A and Singh, H and Nelson, KE and Brinkac, LM}, title = {Integrating the microbiome as a resource in the forensics toolkit.}, journal = {Forensic science international. Genetics}, volume = {30}, number = {}, pages = {141-147}, doi = {10.1016/j.fsigen.2017.06.008}, pmid = {28728057}, issn = {1878-0326}, mesh = {Forensic Genetics/*methods ; *High-Throughput Nucleotide Sequencing ; Humans ; Microbiota/*genetics ; Postmortem Changes ; RNA, Ribosomal, 16S ; Sequence Analysis, RNA ; }, abstract = {The introduction of DNA fingerprinting to forensic science rapidly expanded the available evidence that could be garnered from a crime scene and used in court cases. Next generation sequencing technologies increased available genetic data that could be used as evidence by orders of magnitude, and as such, significant additional genetic information is now available for use in forensic science. This includes DNA from the bacteria that live in and on humans, known as the human microbiome. Next generation sequencing of the human microbiome demonstrates that its bacterial DNA can be used to uniquely identify an individual, provide information about their life and behavioral patterns, determine the body site where a sample came from, and estimate postmortem intervals. Bacterial samples from the environment and objects can also be leveraged to address similar questions about the individual(s) who interacted with them. However, the applications of this new field in forensic sciences raises concerns on current methods used in sample processing, including sample collection, storage, and the statistical power of published studies. These areas of human microbiome research need to be fully addressed before microbiome data can become a regularly incorporated evidence type and routine procedure of the forensic toolkit. Here, we summarize information on the current status of microbiome research as applies to the forensic field, the mathematical models used to make predictions, and the possible legal and practical difficulties that can limit the application of microbiomes in forensic science.}, }
@article {pmid28725438, year = {2017}, author = {Lusi, EA and Patrissi, T and Guarascio, P}, title = {Nickel-resistant bacteria isolated in human microbiome.}, journal = {New microbes and new infections}, volume = {19}, number = {}, pages = {67-70}, pmid = {28725438}, issn = {2052-2975}, abstract = {Nickel-resistant bacteria have been isolated so far only in contaminated soils and wastewaters polluted with different industrial sources. The aim of our study was to determine if nickel-resistant bacteria could also be isolated from human samples. In this brief communication, we describe how we were able to isolate human bacterial strains that grew without oxygen and in the presence of high concentrations of nickel. The identification was made by phenotypic and genetic techniques. The bacterial sequences have been deposited in the NCBI database repository. Our finding shows that there are several different heavy-metal-tolerant bacteria in humans that should be considered for further studies.}, }
@article {pmid28719406, year = {2017}, author = {Maier, KJ and alʼAbsi, M}, title = {Toward a Biopsychosocial Ecology of the Human Microbiome, Brain-Gut Axis, and Health.}, journal = {Psychosomatic medicine}, volume = {79}, number = {8}, pages = {947-957}, doi = {10.1097/PSY.0000000000000515}, pmid = {28719406}, issn = {1534-7796}, mesh = {Brain/*physiology ; Gastrointestinal Microbiome/*physiology ; Humans ; Signal Transduction/*physiology ; }, abstract = {OBJECTIVE: Rapidly expanding insights into the human microbiome and health suggest that Western medicine is poised for significant evolution, or perhaps revolution-this while medicine continues on a trajectory from reductionism to a biopsychosocial (BPS) paradigm recognizing biological, psychological, and social influences on health. The apparent sensitivity of the microbiota to perturbations across BPS domains suggests that a broad and inclusive framework is needed to develop applicable knowledge in this emerging area. We outline an ecological framework of the human microbiome by extending the BPS concept to better incorporate environmental and human factors as members of a global, dynamic set of systems that interact over time.<br><br>METHODS: We conducted a selective literature review across disciplines to integrate microbiome research into a BPS framework.<br><br>RESULTS: The microbiome can be understood in terms of ecological systems encompassing BPS domains at four levels: (a) immediate (molecular, genetic, and neural processes), (b) proximal (physiology, emotion, social integration), (c) intermediate (built environments, behaviors, societal practices), and (d) distal (physical environments, attitudes, and broad cultural, economic, and political factors). The microbiota and host are thus understood in terms of their immediate interactions and the more distal physical and social arenas in which they participate.<br><br>CONCLUSIONS: A BPS ecological paradigm encourages replicable, generalizable, and interdisciplinary/transdisciplinary research and practices that take into account the vast influences on the human microbiome that may otherwise be overlooked or understood out of context. It also underscores the importance of sustainable bioenvironmental, psychological, and social systems that broadly support microbial, neural, and general health.}, }
@article {pmid28719264, year = {2017}, author = {Wood, MR and Yu, EA and Mehta, S}, title = {The Human Microbiome in the Fight Against Tuberculosis.}, journal = {The American journal of tropical medicine and hygiene}, volume = {96}, number = {6}, pages = {1274-1284}, pmid = {28719264}, issn = {1476-1645}, support = {T32 DK007158/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Disease Models, Animal ; *Gastrointestinal Microbiome ; Gastrointestinal Tract/microbiology ; Humans ; Immunomodulation ; Lung/microbiology ; Mycobacterium tuberculosis ; Tuberculosis/microbiology/*therapy ; Tuberculosis, Pulmonary/microbiology/*therapy ; }, abstract = {AbstractThe human microbiome is an intriguing potentially modifiable risk factor in our arsenal against Mycobacterium tuberculosis, the leading infectious disease killer globally. Previous studies have shown associations between the human microbiome and pulmonary disease states; however, etiological links between the microbiome and tuberculosis (TB) infection or disease remain unclear. Immunomodulatory roles of the microbiome may prove to be a critical asset in the host response against TB, including in preventing TB infection, reducing progression from latency, mitigating disease severity, and lowering the incidence of drug resistance and coinfections. This review examined the associations between TB and the gut and lung microbiome. Eight studies were identified through a PubMed database search, including one animal study (N = 1), case report (N = 1), and case-control studies (N = 6). TB infection and disease were associated with reduced gastrointestinal microbial diversity in a murine model and human case report. Sputum microbial diversity differed by TB status in case-control studies, although some reported heterogeneous findings. Current evidence suggests that the gut and lung microbiome are associated with TB infection and disease. However, as studies are limited, etiological and longitudinal research is needed to determine clinical relevance.}, }
@article {pmid28718274, year = {2017}, author = {Suárez Moya, A}, title = {[Microbiome and next generation sequencing].}, journal = {Revista espanola de quimioterapia : publicacion oficial de la Sociedad Espanola de Quimioterapia}, volume = {30}, number = {5}, pages = {305-311}, pmid = {28718274}, issn = {1988-9518}, mesh = {Biodiversity ; DNA, Bacterial/*analysis ; *High-Throughput Nucleotide Sequencing ; Humans ; Microbiota/*genetics ; Sequence Analysis, DNA/*methods ; }, abstract = {The human microbiome is an internal ecosystem that refers to the community of microorganisms that populate the human body. These microorganisms are essential to support his health, because the interaction between the host immune system and microorganisms, provide the host with protection against pathogens, and contributes to the preservation of health. Bacteriological culture has been the basis for traditional microbiology; however, most of the bacterial forms observed in nature cannot be isolated with laboratory culture methods. At present, metagenomic applies a suite of genomic technologies, where the microorganisms are identified by their genomic fingerprint. The 16S rRNA subunit is considered as the universal target for bacterial identification from DNA with the aid of sequencing. Sanger sequencing technology had a great impact on the first generation sequencing due to its simplicity and precision. Platforms high-throughput known as second generation secuencing technologies are capable to generate hundreds of thousands of sequence reactions in a faster and economic way. However, thanks to the third generation sequencing the greatest advances in nanotechnology have been made. Using the reference gene, the massive sequencing techniques and bioinformatics tools used for the data processing, there has been an important development of the human microbiome, achieving an unprecedented detail level on the taxonomy and microbial function. This has meant an authentic revolution not only in their knowledge but also in their involvement in the health or illness of the human being.}, }
@article {pmid28713344, year = {2017}, author = {Poppleton, DI and Duchateau, M and Hourdel, V and Matondo, M and Flechsler, J and Klingl, A and Beloin, C and Gribaldo, S}, title = {Outer Membrane Proteome of Veillonella parvula: A Diderm Firmicute of the Human Microbiome.}, journal = {Frontiers in microbiology}, volume = {8}, number = {}, pages = {1215}, pmid = {28713344}, issn = {1664-302X}, abstract = {Veillonella parvula is a biofilm-forming commensal found in the lungs, vagina, mouth, and gastro-intestinal tract of humans, yet it may develop into an opportunistic pathogen. Furthermore, the presence of Veillonella has been associated with the development of a healthy immune system in infants. Veillonella belongs to the Negativicutes, a diverse clade of bacteria that represent an evolutionary enigma: they phylogenetically belong to Gram-positive (monoderm) Firmicutes yet maintain an outer membrane (OM) with lipopolysaccharide similar to classic Gram-negative (diderm) bacteria. The OMs of Negativicutes have unique characteristics including the replacement of Braun's lipoprotein by OmpM for tethering the OM to the peptidoglycan. Through phylogenomic analysis, we have recently provided bioinformatic annotation of the Negativicutes diderm cell envelope. We showed that it is a unique type of envelope that was present in the ancestor of present-day Firmicutes and lost multiple times independently in this phylum, giving rise to the monoderm architecture; however, little experimental data is presently available for any Negativicutes cell envelope. Here, we performed the first experimental proteomic characterization of the cell envelope of a diderm Firmicute, producing an OM proteome of V. parvula. We initially conducted a thorough bioinformatics analysis of all 1,844 predicted proteins from V. parvula DSM 2008's genome using 12 different localization prediction programs. These results were complemented by protein extraction with surface exposed (SE) protein tags and by subcellular fractionation, both of which were analyzed by liquid chromatography tandem mass spectrometry. The merging of proteomics and bioinformatics results allowed identification of 78 OM proteins. These include a number of receptors for TonB-dependent transport, the main component of the BAM system for OM protein biogenesis (BamA), the Lpt system component LptD, which is responsible for insertion of LPS into the OM, and several copies of the major OmpM protein. The annotation of V. parvula's OM proteome markedly extends previous inferences on the nature of the cell envelope of Negativicutes, including the experimental evidence of a BAM/TAM system for OM protein biogenesis and of a complete Lpt system for LPS transport to the OM. It also provides important information on the role of OM components in the lifestyle of Veillonella, such as a possible gene cluster for O-antigen synthesis and a large number of adhesins. Finally, many OM hypothetical proteins were identified, which are priority targets for further characterization.}, }
@article {pmid28711782, year = {2017}, author = {Blum, HE}, title = {The human microbiome.}, journal = {Advances in medical sciences}, volume = {62}, number = {2}, pages = {414-420}, doi = {10.1016/j.advms.2017.04.005}, pmid = {28711782}, issn = {1898-4002}, mesh = {Bacteria ; *Bacterial Physiological Phenomena ; Biodiversity ; *Disease ; Humans ; *Microbiota ; }, abstract = {Until recently, human microbiology was based on the identification of single microbes, such as bacteria, fungi and viruses, frequently isolated from patients with acute or chronic infections. Novel culture-independent molecular biochemical analyses (genomics, transcriptomics, proteomics, metabolomics) allow today to detect and classify the diverse microorganisms in a given ecosystem (microbiota), such as the gastrointestinal tract, the skin, the airway system, the urogenital tract and others, and to assess all genomes in these ecosystems (microbiome) as well as their gene products. These analyses revealed that each individual has its own microbiota that plays a role in health and disease. In addition, they greatly contributed to the recent advances in the understanding of the pathogenesis of a wide range of human diseases. It is to be expected that these new insights will translate into diagnostic, therapeutic and preventive measures in the context of personalized/precision medicine.}, }
@article {pmid28706916, year = {2017}, author = {Ruiz-Rodriguez, M and Rello, J}, title = {Human microbiome in respiratory diseases.}, journal = {Annals of translational medicine}, volume = {5}, number = {12}, pages = {248}, pmid = {28706916}, issn = {2305-5839}, }
@article {pmid28704437, year = {2017}, author = {Lai, PS and Allen, JG and Hutchinson, DS and Ajami, NJ and Petrosino, JF and Winters, T and Hug, C and Wartenberg, GR and Vallarino, J and Christiani, DC}, title = {Impact of environmental microbiota on human microbiota of workers in academic mouse research facilities: An observational study.}, journal = {PloS one}, volume = {12}, number = {7}, pages = {e0180969}, pmid = {28704437}, issn = {1932-6203}, support = {K23 ES023700/ES/NIEHS NIH HHS/United States ; P30 ES000002/ES/NIEHS NIH HHS/United States ; T32 ES007069/ES/NIEHS NIH HHS/United States ; T42 OH008416/OH/NIOSH CDC HHS/United States ; }, mesh = {Air Pollutants, Occupational/analysis ; Animal Technicians ; Animals ; Bacteria/*classification/genetics ; DNA, Bacterial/genetics ; Endotoxins/*genetics ; Humans ; Medical Laboratory Personnel ; Mice ; *Microbiota ; Mouth/microbiology ; Nose/microbiology ; Occupational Exposure/*classification ; RNA, Ribosomal, 16S/*genetics ; Skin/microbiology ; }, abstract = {OBJECTIVES: To characterize the microbial environment of workers in academic mouse research facilities using endotoxin, 16S qPCR, and 16S amplicon sequencing. To determine whether the work microbiome contributes to the human microbiome of workers.<br><br>METHODS: We performed area air sampling from the animal rooms, dirty, middle, and setup cage wash locations in four academic mouse research facilities. 10 workers in the dirty cage wash area underwent personal air sampling as well as repeated collection of nasal, oral, and skin samples before and after the work shift. Environmental samples underwent measurement of endotoxin, mouse allergen, bacteria copy number via 16S qPCR, and microbial identification via 16S rDNA sequencing. 16S rDNA sequencing was also performed on human samples before and after the work shift. SourceTracker was used to identify the contribution of the work microbiome to the human microbiome.<br><br>RESULTS: Median endotoxin levels ranged from undetectable to 1.0 EU/m3. Significant differences in mouse allergen levels, bacterial copy number, microbial richness, and microbial community structure were identified between animal, dirty, middle, and setup cage wash locations. Endotoxin levels had only a moderate correlation with microbial composition. Location within a facility was a stronger predictor of microbial community composition (R2 = 0.41, p = 0.002) than facility. The contribution of the work microbiome to the pre-shift human microbiome of workers was estimated to be 0.1 &#xb1; 0.1% for the oral microbiome; 3.1 &#xb1; 1.9% for the nasal microbiome; and 3.0 &#xb1; 1.5% for the skin microbiome.<br><br>CONCLUSIONS: The microbial environment of academic animal care facilities varies significantly by location rather than facility. Endotoxin is not a proxy for assessment of environmental microbial exposures using 16S qPCR or 16S rDNA sequencing. The work microbiome contributes to the composition of the nasal and skin microbiome of workers; the clinical implications of this observation should be further studied.}, }
@article {pmid28702202, year = {2017}, author = {Diop, A and Raoult, D and Fenollar, F and Fournier, PE}, title = {'Khoudiadiopia massiliensis' gen. nov., sp. nov., strain Marseille-P2746T[T], a new bacterial genus isolated from the female genital tract.}, journal = {New microbes and new infections}, volume = {19}, number = {}, pages = {60-61}, pmid = {28702202}, issn = {2052-2975}, abstract = {We report the main characteristics of 'Khoudiadiopia massiliensis' gen. nov., sp. nov., strain Marseille-P2746[T] (= CSUR P2746), a new member of the Peptoniphilaceae family isolated from a vaginal swab of a patient suffering from bacterial vaginosis.}, }
@article {pmid28696940, year = {2017}, author = {Quagliariello, A and De Fanti, S and Giuliani, C and Abondio, P and Serventi, P and Sarno, S and Sazzini, M and Luiselli, D}, title = {Multiple selective events at the PRDM16 functional pathway shaped adaptation of western European populations to different climate conditions.}, journal = {Journal of anthropological sciences = Rivista di antropologia : JASS}, volume = {95}, number = {}, pages = {235-247}, doi = {10.4436/JASS.95011}, pmid = {28696940}, issn = {2037-0644}, mesh = {Adaptation, Biological/*genetics ; Body Temperature Regulation/genetics ; *Climate ; DNA-Binding Proteins/*genetics ; Europe ; Haplotypes/genetics ; Humans ; Polymorphism, Single Nucleotide/genetics ; Selection, Genetic/*genetics ; Transcription Factors/*genetics ; White People/genetics ; }, abstract = {Several studies highlighted the role of climate in shaping many human evolutionary processes. This occurred even in relatively recent times, having affected various human phenotypic traits, among which metabolic processes that orchestrate absorption and accumulation of substances to maintain energy homeostasis, that is critical for the survival of individuals in high energy-expenditure environments. To date, most researches have focalized on detection of climatic influence on SNPs' frequency in populations exposed to extreme environmental conditions or by comparing variation patterns between populations from different continents. In this study, we instead explored the genetic background of distinct western European human groups at loci involved in nutritional and thermoregulation processes, to test whether patterns of differential local adaptation to environmental conditions could be appreciated also at a lower geographical scale. Taking advantage from the 1000 Genomes Project data, genetic information for 21 genes involved in nutritional and thermoregulation processes was analysed for three western European populations. The applied Anthropological Genetics methods pointed to appreciable differentiation between the examined groups especially for the PRDM16 gene. Moreover, several neutrality tests suggested that balancing selection has acted on different regions of the gene in people from Great Britain, as well as that more recent positive selection could have also targeted some PRDM16 SNPs in Finn and Italian populations. These series of adaptive footprints are plausibly related to climate variability in both ancient and relatively recent times. Since this locus is involved in thermoregulation mechanisms and adipogenesis, local adaptations mediated by a pathway related to the brown adipose tissue activity could have evolved in response to changing cold temperature exposures of such populations.}, }
@article {pmid28690602, year = {2017}, author = {Gupta, VK and Paul, S and Dutta, C}, title = {Geography, Ethnicity or Subsistence-Specific Variations in Human Microbiome Composition and Diversity.}, journal = {Frontiers in microbiology}, volume = {8}, number = {}, pages = {1162}, pmid = {28690602}, issn = {1664-302X}, abstract = {One of the fundamental issues in the microbiome research is characterization of the healthy human microbiota. Recent studies have elucidated substantial divergences in the microbiome structure between healthy individuals from different race and ethnicity. This review provides a comprehensive account of such geography, ethnicity or life-style-specific variations in healthy microbiome at five major body habitats-Gut, Oral-cavity, Respiratory Tract, Skin, and Urogenital Tract (UGT). The review focuses on the general trend in the human microbiome evolution-a gradual transition in the gross compositional structure along with a continual decrease in diversity of the microbiome, especially of the gut microbiome, as the human populations passed through three stages of subsistence like foraging, rural farming and industrialized urban western life. In general, gut microbiome of the hunter-gatherer populations is highly abundant with Prevotella, Proteobacteria, Spirochaetes, Clostridiales, Ruminobacter etc., while those of the urban communities are often enriched in Bacteroides, Bifidobacterium, and Firmicutes. The oral and skin microbiome are the next most diverse among different populations, while respiratory tract and UGT microbiome show lesser variations. Higher microbiome diversity is observed for oral-cavity in hunter-gatherer group with higher prevalence of Haemophilus than agricultural group. In case of skin microbiome, rural and urban Chinese populations show variation in abundance of Trabulsiella and Propionibacterium. On the basis of published data, we have characterized the core microbiota-the set of genera commonly found in all populations, irrespective of their geographic locations, ethnicity or mode of subsistence. We have also identified the major factors responsible for geography-based alterations in microbiota; though it is not yet clear which factor plays a dominant role in shaping the microbiome-nature or nurture, host genetics or his environment. Some of the geographical/racial variations in microbiome structure have been attributed to differences in host genetics and innate/adaptive immunity, while in many other cases, cultural/behavioral features like diet, hygiene, parasitic load, environmental exposure etc. overshadow genetics. The ethnicity or population-specific variations in human microbiome composition, as reviewed in this report, question the universality of the microbiome-based therapeutic strategies and recommend for geographically tailored community-scale approaches to microbiome engineering.}, }
@article {pmid28676754, year = {2017}, author = {Emery, DC and Shoemark, DK and Batstone, TE and Waterfall, CM and Coghill, JA and Cerajewska, TL and Davies, M and West, NX and Allen, SJ}, title = {16S rRNA Next Generation Sequencing Analysis Shows Bacteria in Alzheimer's Post-Mortem Brain.}, journal = {Frontiers in aging neuroscience}, volume = {9}, number = {}, pages = {195}, pmid = {28676754}, issn = {1663-4365}, abstract = {The neurological deterioration associated with Alzheimer's disease (AD), involving accumulation of amyloid-beta peptides and neurofibrillary tangles, is associated with evident neuroinflammation. This is now seen to be a significant contributor to pathology. Recently the tenet of the privileged status of the brain, regarding microbial compromise, has been questioned, particularly in terms of neurodegenerative diseases. It is now being considered that microbiological incursion into the central nervous system could be either an initiator or significant contributor to these. This is a novel study using 16S ribosomal gene-specific Next generation sequencing (NGS) of extracted brain tissue. A comparison was made of the bacterial species content of both frozen and formaldehyde fixed sections of a small cohort of Alzheimer-affected cases with those of cognitively unimpaired (normal). Our findings suggest an increase in bacterial populations in Alzheimer brain tissue compared with normal.}, }
@article {pmid28669823, year = {2017}, author = {Wefers, D and Cavalcante, JJV and Schendel, RR and Deveryshetty, J and Wang, K and Wawrzak, Z and Mackie, RI and Koropatkin, NM and Cann, I}, title = {Biochemical and Structural Analyses of Two Cryptic Esterases in Bacteroides intestinalis and their Synergistic Activities with Cognate Xylanases.}, journal = {Journal of molecular biology}, volume = {429}, number = {16}, pages = {2509-2527}, doi = {10.1016/j.jmb.2017.06.017}, pmid = {28669823}, issn = {1089-8638}, mesh = {Amino Acid Sequence ; Bacteroides/*enzymology ; Caffeic Acids/metabolism ; Chromatography, Gel ; Coumaric Acids/metabolism ; Crystallography, X-Ray ; Esterases/*chemistry/*metabolism ; Kinetics ; Magnetic Resonance Spectroscopy ; Molecular Sequence Data ; Protein Conformation ; Protein Multimerization ; Sequence Alignment ; Substrate Specificity ; Xylans/metabolism ; Xylosidases/*metabolism ; }, abstract = {Arabinoxylans are constituents of the human diet. Although not utilizable by the human host, they can be fermented by colonic bacteria. The arabinoxylan backbone is decorated with arabinose side chains that may be substituted with ferulic acid, thus limiting depolymerization to fermentable sugars. We investigated the polypeptides encoded by two genes upregulated during growth of the colonic bacterium Bacteroides intestinalis on wheat arabinoxylan. The recombinant proteins, designated BiFae1A and BiFae1B, were functionally assigned esterase activities. Both enzymes were active on acetylated substrates, although each showed a higher ferulic acid esterase activity on methyl-ferulate. BiFae1A showed a catalytic efficiency of 12mM s[-1] on para-nitrophenyl-acetate, and on methyl-ferulate, the value was 27 times higher. BiFae1B showed low catalytic efficiencies for both substrates. Furthermore, the two enzymes released ferulic acid from various structural elements, and NMR spectroscopy indicated complete de-esterification of arabinoxylan oligosaccharides from wheat bran. BiFae1A is a tetramer based on the crystal structure, whereas BiFae1B is a dimer in solution based on size exclusion chromatography. The structure of BiFae1A was solved to 1.98Å resolution, and two tetramers were observed in the asymmetric unit. A flexible loop that may act as a hinge over the active site and likely coordinates critical interactions with the substrate was prominent in BiFae1A. Sequence alignments of the esterase domains in BiFae1B with the feruloyl esterase from Clostridium thermocellum suggest that both domains lack the flexible hinge in BiFae1A, an observation that may partly provide a molecular basis for the differences in activities in the two esterases.}, }
@article {pmid28667752, year = {2017}, author = {Madhoolika, B and Anil Kumar, NV and Balaji, S}, title = {In vitro analysis of 4-methylumbelliferone as a sole carbon source for Lactobacillus helveticus 2126.}, journal = {Letters in applied microbiology}, volume = {65}, number = {3}, pages = {249-255}, doi = {10.1111/lam.12772}, pmid = {28667752}, issn = {1472-765X}, mesh = {Carbon/metabolism ; Culture Media/metabolism ; Humans ; Hymecromone/*metabolism ; Lactobacillus helveticus/genetics/growth &amp; development/*metabolism ; Probiotics/metabolism ; }, abstract = {UNLABELLED: In the recent years, 4-methylumbelliferone (4-MU) has been gaining importance, both as an anti-cancer agent and as a dietary supplement. The aim of this study was to determine the effectiveness of 4-MU as a carbon source for potential probiotic bacteria Lactobacillus helveticus 2126. For this purpose, a series of plate assays and infrared spectroscopy (FTIR) were used for 4-MU before and after the treatment with L. helveticus 2126. The plate assays indicated an initial inhibition followed by utilization of 4-MU that stimulated bacterial growth. A significant shift was observed in the FTIR peaks, which also have suggested possible extracellular activity of the bacteria for 4-MU utilization.<br><br>4-Methylumbelliferone (4-MU) is a widely used chloretic and is currently under research for treating colon cancer. Preliminary studies suggest that it has the potential to be used as an effective and sustainable prebiotic for the human microbiome, as it can be naturally obtained from plants. This manuscript describes the effectiveness of 4-MU as a carbon source for the probiotic bacteria Lactobacillus helveticus. Our study also suggests the role of bacterial superoxide dismutase in transforming 4-MU as a possible prebiotic for the human microbiome.}, }
@article {pmid28667113, year = {2017}, author = {Özcan, E and Sun, J and Rowley, DC and Sela, DA}, title = {A Human Gut Commensal Ferments Cranberry Carbohydrates To Produce Formate.}, journal = {Applied and environmental microbiology}, volume = {83}, number = {17}, pages = {}, pmid = {28667113}, issn = {1098-5336}, support = {P20 GM103430/GM/NIGMS NIH HHS/United States ; }, abstract = {Commensal bifidobacteria colonize the human gastrointestinal tract and catabolize glycans that are impervious to host digestion. Accordingly, Bifidobacterium longum typically secretes acetate and lactate as fermentative end products. This study tested the hypothesis that B. longum utilizes cranberry-derived xyloglucans in a strain-dependent manner. Interestingly, the B. longum strain that efficiently utilizes cranberry xyloglucans secretes 2.0 to 2.5 mol of acetate-lactate. The 1.5 acetate:lactate ratio theoretical yield obtained in hexose fermentations shifts during xyloglucan metabolism. Accordingly, this metabolic shift is characterized by increased acetate and formate production at the expense of lactate. α-l-Arabinofuranosidase, an arabinan endo-1,5-α-l-arabinosidase, and a β-xylosidase with a carbohydrate substrate-binding protein and carbohydrate ABC transporter membrane proteins are upregulated (>2-fold change), which suggests carbon flux through this catabolic pathway. Finally, syntrophic interactions occurred with strains that utilize carbohydrate products derived from initial degradation from heterologous bacteria.IMPORTANCE This was a study of bacterial metabolism of complex cranberry carbohydrates termed xyloglucans that are likely not digested prior to reaching the colon. This is significant, as bifidobacteria interact with this dietary compound to potentially impact human host health through energy and metabolite production by utilizing these substrates. Specific bacterial strains utilize cranberry xyloglucans as a nutritive source, indicating unknown mechanisms that are not universal in bifidobacteria. In addition, xyloglucan metabolism proceeds by using an alternative pathway that could lead to further research to investigate mechanisms underlying this interaction. Finally, we observed cross-feeding between bacteria in which one strain degrades the cranberry xyloglucan to make it available to a second strain. Similar nutritive strategies are known to occur within the gut. In aggregate, this study may lead to novel foods or supplements used to impact human health through rational manipulation of the human microbiome.}, }
@article {pmid28659968, year = {2017}, author = {Sandoval-Motta, S and Aldana, M and Martínez-Romero, E and Frank, A}, title = {The Human Microbiome and the Missing Heritability Problem.}, journal = {Frontiers in genetics}, volume = {8}, number = {}, pages = {80}, pmid = {28659968}, issn = {1664-8021}, abstract = {The "missing heritability" problem states that genetic variants in Genome-Wide Association Studies (GWAS) cannot completely explain the heritability of complex traits. Traditionally, the heritability of a phenotype is measured through familial studies using twins, siblings and other close relatives, making assumptions on the genetic similarities between them. When this heritability is compared to the one obtained through GWAS for the same traits, a substantial gap between both measurements arise with genome wide studies reporting significantly smaller values. Several mechanisms for this "missing heritability" have been proposed, such as epigenetics, epistasis, and sequencing depth. However, none of them are able to fully account for this gap in heritability. In this paper we provide evidence that suggests that in order for the phenotypic heritability of human traits to be broadly understood and accounted for, the compositional and functional diversity of the human microbiome must be taken into account. This hypothesis is based on several observations: (A) The composition of the human microbiome is associated with many important traits, including obesity, cancer, and neurological disorders. (B) Our microbiome encodes a second genome with nearly a 100 times more genes than the human genome, and this second genome may act as a rich source of genetic variation and phenotypic plasticity. (C) Human genotypes interact with the composition and structure of our microbiome, but cannot by themselves explain microbial variation. (D) Microbial genetic composition can be strongly influenced by the host's behavior, its environment or by vertical and horizontal transmissions from other hosts. Therefore, genetic similarities assumed in familial studies may cause overestimations of heritability values. We also propose a method that allows the compositional and functional diversity of our microbiome to be incorporated to genome wide association studies.}, }
@article {pmid28658154, year = {2017}, author = {Ashton, JJ and Colquhoun, CM and Cleary, DW and Coelho, T and Haggarty, R and Mulder, I and Batra, A and Afzal, NA and Beattie, RM and Scott, KP and Ennis, S}, title = {16S sequencing and functional analysis of the fecal microbiome during treatment of newly diagnosed pediatric inflammatory bowel disease.}, journal = {Medicine}, volume = {96}, number = {26}, pages = {e7347}, pmid = {28658154}, issn = {1536-5964}, mesh = {Adolescent ; Biodiversity ; Child ; Fatty Acids, Volatile/analysis ; Feces/chemistry/*microbiology ; Female ; Gastrointestinal Microbiome/*genetics ; Humans ; Inflammatory Bowel Diseases/genetics/metabolism/*microbiology/*therapy ; Longitudinal Studies ; Male ; Prospective Studies ; RNA, Bacterial/*analysis ; RNA, Ribosomal, 16S/*analysis ; Sequence Analysis, RNA ; Siblings ; Treatment Outcome ; }, abstract = {The human microbiome is of considerable interest to pediatric inflammatory bowel disease (PIBD) researchers with 1 potential mechanism for disease development being aberrant immune handling of the intestinal bacteria. This study analyses the fecal microbiome through treatment in newly diagnosed PIBD patients and compares to cohabiting siblings where possible. Patients were recruited on clinical suspicion of PIBD before diagnosis. Treatment-naïve fecal samples were collected, with further samples at 2 and 6 weeks into treatment. Samples underwent 16S ribosomal ribonucleic acid (RNA) gene sequencing and short-chain fatty acids (SCFAs) analysis, results were analyzed using quantitative-insights-into-microbial-ecology. Six PIBD patients were included in the cohort: 4 Crohn disease (CD), 1 ulcerative colitis (UC), 1 inflammatory bowel disease (IBD) unclassified, and median age 12.6 (range 10-15.1 years); 3 patients had an unaffected healthy sibling recruited. Microbial diversity (observed species/Chao1/Shannon diversity) was reduced in treatment-naïve patients compared to siblings and patients in remission. Principal coordinate analysis using Bray-Curtis dissimilarity and UniFrac revealed microbial shifts in CD over the treatment course. In treatment-naïve PIBD, there was reduction in functional ability for amino acid metabolism and carbohydrate handling compared to controls (P = .038) and patients in remission (P = .027). Metabolic function returned to normal after remission was achieved. SCFA revealed consistent detection of lactate in treatment-naïve samples. This study adds in-depth 16S rRNA sequencing analysis on a small longitudinal cohort to the literature and includes sibling controls and patients with UC/IBD unclassified. It highlights the initial dysbiosis, reduced diversity, altered functional potential, and subsequent shifts in bacteria from diagnosis over time to remission.}, }
@article {pmid28648295, year = {2017}, author = {Caradonna, T and Marangi, M and Del Chierico, F and Ferrari, N and Reddel, S and Bracaglia, G and Normanno, G and Putignani, L and Giangaspero, A}, title = {Detection and prevalence of protozoan parasites in ready-to-eat packaged salads on sale in Italy.}, journal = {Food microbiology}, volume = {67}, number = {}, pages = {67-75}, doi = {10.1016/j.fm.2017.06.006}, pmid = {28648295}, issn = {1095-9998}, mesh = {Cryptosporidium/genetics/growth &amp; development/*isolation &amp; purification ; Cyclospora/genetics/growth &amp; development/*isolation &amp; purification ; DNA, Protozoan ; Fast Foods/*parasitology ; Food Contamination/analysis/*statistics &amp; numerical data ; Italy ; Toxoplasma/genetics/growth &amp; development/*isolation &amp; purification ; Vegetables/*parasitology ; }, abstract = {To investigate the prevalence of protozoan contamination by Giardia duodenalis, Cryptosporidium spp., Toxoplasma gondii and Cyclospora cayetanensis, in 'ready to eat' (RTE) salads on sale in Italy, 648 packages were purchased from industrial and local brands. Nine individual packages from each brand were collected per month, pooled and subjected to microscopy and molecular analyses. Microscopic examination of 864 slides detected Cryptosporidium spp. but also Blastocystis hominis and Dientamoeba fragilis. Molecular tools identified G. duodenalis assemblage A, Cryptosporidium parvum and Cryptosporidium ubiquitum, T. gondii Type I and C. cayetanensis. B. hominis and D. fragilis were also molecularly confirmed. The overall prevalence of each protozoan species was 0.6% for G. duodenalis, 0.8% for T. gondii, 0.9% for Cryptosporidium spp., and 1.3% for C. cayetanensis, while prevalence for B. hominis was 0.5% and for D. fragilis 0.2%. Microscopy and/or molecular tools revealed that 4.2% of the samples were contaminated by at least one protozoan species, and 0.6% of samples presented contamination by two protozoan species, with a number of oocysts ranging from 62 to 554 per g of vegetable matter for T. gondii, and 46 to 1.580 for C. cayetanensis. This is Europe's first large-scale study on the presence of protozoans in packaged salads, and shows that RTE sanitation processes do not guarantee a product free from protozoans of fecal origin.}, }
@article {pmid28644475, year = {2017}, author = {Benjdia, A and Guillot, A and Ruffié, P and Leprince, J and Berteau, O}, title = {Post-translational modification of ribosomally synthesized peptides by a radical SAM epimerase in Bacillus subtilis.}, journal = {Nature chemistry}, volume = {9}, number = {7}, pages = {698-707}, pmid = {28644475}, issn = {1755-4349}, mesh = {Bacillus subtilis/enzymology/*metabolism ; Free Radicals/chemistry/metabolism ; Molecular Conformation ; Peptides/*metabolism ; *Protein Biosynthesis ; *Protein Processing, Post-Translational ; Ribosomes/*metabolism ; S-Adenosylmethionine/*metabolism ; }, abstract = {Ribosomally synthesized peptides are built out of L-amino acids, whereas D-amino acids are generally the hallmark of non-ribosomal synthetic processes. Here we show that the model bacterium Bacillus subtilis is able to produce a novel type of ribosomally synthesized and post-translationally modified peptide that contains D-amino acids, and which we propose to call epipeptides. We demonstrate that a two [4Fe-4S]-cluster radical S-adenosyl-L-methionine (SAM) enzyme converts L-amino acids into their D-counterparts by catalysing Cα-hydrogen-atom abstraction and using a critical cysteine residue as the hydrogen-atom donor. Unexpectedly, these D-amino acid residues proved to be essential for the activity of a peptide that induces the expression of LiaRS, a major component of the bacterial cell envelope stress-response system. Present in B. subtilis and in several members of the human microbiome, these epipeptides and radical SAM epimerases broaden the landscape of peptidyl structures accessible to living organisms.}, }
@article {pmid28632755, year = {2017}, author = {Yost, S and Duran-Pinedo, AE and Krishnan, K and Frias-Lopez, J}, title = {Potassium is a key signal in host-microbiome dysbiosis in periodontitis.}, journal = {PLoS pathogens}, volume = {13}, number = {6}, pages = {e1006457}, pmid = {28632755}, issn = {1553-7374}, support = {R01 DE021553/DE/NIDCR NIH HHS/United States ; }, mesh = {Bacteria/classification/genetics/*isolation &amp; purification ; Dysbiosis/immunology/*microbiology ; Gingiva/immunology/microbiology ; Humans ; Interleukin-6/immunology ; *Microbiota ; Mouth/immunology/*microbiology ; Periodontitis/immunology/*microbiology ; Phylogeny ; Potassium/*immunology ; Tumor Necrosis Factor-alpha/immunology ; beta-Defensins/immunology ; }, abstract = {Dysbiosis, or the imbalance in the structural and/or functional properties of the microbiome, is at the origin of important infectious inflammatory diseases such as inflammatory bowel disease (IBD) and periodontal disease. Periodontitis is a polymicrobial inflammatory disease that affects a large proportion of the world's population and has been associated with a wide variety of systemic health conditions, such as diabetes, cardiovascular and respiratory diseases. Dysbiosis has been identified as a key element in the development of the disease. However, the precise mechanisms and environmental signals that lead to the initiation of dysbiosis in the human microbiome are largely unknown. In a series of previous in vivo studies using metatranscriptomic analysis of periodontitis and its progression we identified several functional signatures that were highly associated with the disease. Among them, potassium ion transport appeared to be key in the process of pathogenesis. To confirm its importance we performed a series of in vitro experiments, in which we demonstrated that potassium levels a increased the virulence of the oral community as a whole and at the same time altering the immune response of gingival epithelium, increasing the production of TNF-α and reducing the expression of IL-6 and the antimicrobial peptide human β-defensin 3 (hBD-3). These results indicate that levels of potassium in the periodontal pocket could be an important element in of dysbiosis in the oral microbiome. They are a starting point for the identification of key environmental signals that modify the behavior of the oral microbiome from a symbiotic community to a dysbiotic one.}, }
@article {pmid28626612, year = {2017}, author = {DeBruyn, JM and Hauther, KA}, title = {Postmortem succession of gut microbial communities in deceased human subjects.}, journal = {PeerJ}, volume = {5}, number = {}, pages = {e3437}, pmid = {28626612}, issn = {2167-8359}, abstract = {The human microbiome has demonstrated an importance for the health and functioning in living individuals. However, the fate of the microbiome after death is less understood. In addition to a better understanding of microbe-mediated decomposition processes, postmortem succession of human-associated microbial communities has been suggested as a possible forensic tool for estimating time since death, or postmortem interval (PMI). The objective of our study was to document postmortem changes in human gut bacterial communities. Gut microflora were repeatedly sampled from the caeca of cadavers as they decayed under natural environmental conditions. 16S rRNA gene amplicon sequencing revealed that over time, bacterial richness significantly increased (rs = 0.449) while diversity decreased (rs = - 0.701). The composition of gut bacterial communities changed in a similar manner over time towards a common decay community. OTUs belonging to Bacteroidales (Bacteroides, Parabacteroides) significantly declined while Clostridiales (Clostridium, Anaerosphaera) and the fly-associated Gammaproteobacteria Ignatzschineria and Wohlfahrtiimonas increased. Our examination of human caeca microflora in decomposing cadavers adds to the growing literature on postmortem microbial communities, which will ultimately contribute to a better understanding of decomposition processes.}, }
@article {pmid28615076, year = {2017}, author = {Tolonen, AC and Xavier, RJ}, title = {Dissecting the human microbiome with single-cell genomics.}, journal = {Genome medicine}, volume = {9}, number = {1}, pages = {56}, pmid = {28615076}, issn = {1756-994X}, support = {P30 DK043351/DK/NIDDK NIH HHS/United States ; U54 DK102557/DK/NIDDK NIH HHS/United States ; }, mesh = {Bacteria/*genetics ; *Genome, Bacterial ; Genomics/*methods ; Humans ; *Microbiota ; Sequence Analysis, DNA/*methods ; }, abstract = {Recent advances in genome sequencing of single microbial cells enable the assignment of functional roles to members of the human microbiome that cannot currently be cultured. This approach can reveal the genomic basis of phenotypic variation between closely related strains and can be applied to the targeted study of immunogenic bacteria in disease.}, }
@article {pmid28600901, year = {2017}, author = {Jatzlauk, G and Bartel, S and Heine, H and Schloter, M and Krauss-Etschmann, S}, title = {Influences of environmental bacteria and their metabolites on allergies, asthma, and host microbiota.}, journal = {Allergy}, volume = {72}, number = {12}, pages = {1859-1867}, doi = {10.1111/all.13220}, pmid = {28600901}, issn = {1398-9995}, mesh = {Age Factors ; Animals ; Asthma/epidemiology/*etiology/prevention &amp; control ; Bacteria/*immunology/metabolism ; Environment ; Environmental Exposure/*adverse effects ; Host-Pathogen Interactions/*immunology ; Humans ; Hypersensitivity/epidemiology/*etiology/prevention &amp; control ; Immunomodulation ; *Microbiota ; Models, Animal ; Pulmonary Alveoli/immunology/metabolism ; Respiratory Mucosa/immunology/microbiology ; }, abstract = {The prevalence of allergic diseases and asthma has dramatically increased over the last decades, resulting in a high burden for patients and healthcare systems. Thus, there is an unmet need to develop preventative strategies for these diseases. Epidemiological studies show that reduced exposure to environmental bacteria in early life (eg, birth by cesarean section, being formula-fed, growing up in an urban environment or with less contact to various persons) is associated with an increased risk to develop allergies and asthma later in life. Conversely, a reduced risk for asthma is consistently found in children growing up on traditional farms, thereby being exposed to a wide spectrum of microbes. However, clinical studies with bacteria to prevent allergic diseases are still rare and to some extent contradicting. A detailed mechanistic understanding of how environmental microbes influence the development of the human microbiome and the immune system is important to enable the development of novel preventative approaches that are based on the early modulation of the host microbiota and immunity. In this mini-review, we summarize current knowledge and experimental evidence for the potential of bacteria and their metabolites to be used for the prevention of asthma and allergic diseases.}, }
@article {pmid28594642, year = {2017}, author = {McElroy, KG and Chung, SY and Regan, M}, title = {CE: Health and the Human Microbiome: A Primer for Nurses.}, journal = {The American journal of nursing}, volume = {117}, number = {7}, pages = {24-30}, doi = {10.1097/01.NAJ.0000520917.73358.99}, pmid = {28594642}, issn = {1538-7488}, mesh = {*Curriculum ; Education, Nursing, Continuing ; Evidence-Based Nursing/*education ; Female ; Gastrointestinal Tract/*microbiology ; Humans ; Microbiota/*physiology ; Nursing Staff/*education ; Vagina/*microbiology ; }, abstract = {: The profound impact of the human microbiome on health makes it imperative that nurses understand the basic structures and functions of the various microbial communities. In studying the human microbiome, advances in DNA and RNA sequencing technology offer benefits over traditional culture-based methods. Such technology has permitted more thorough investigations of microbial communities, particularly those of the gastrointestinal (GI) and female reproductive tracts. Although individual variations exist, each site exhibits distinct compositions. The diverse GI microbiota aid in digestion, mood regulation, and vitamin synthesis. While many factors affect the composition and functions of the GI microbiota, diet likely exerts the strongest influence. Vaginal microbiota tend to be less diverse, and mainly serve to protect women from infection. The composition of the vaginal microbiota is influenced by sexual activity, hygienic practices, medications, smoking, and other factors. Our increasing knowledge about the structures and functions of the GI and vaginal microbiota allows nurses to provide targeted, evidence-based education and care for various populations.}, }
@article {pmid28587343, year = {2017}, author = {Dong, T and Feng, Q and Liu, F and Chang, LK and Zhou, X and Han, M and Tian, X and Zhong, N and Liu, S}, title = {Alteration of stomach microbiota compositions in the progression of gastritis induces nitric oxide in gastric cell.}, journal = {Experimental and therapeutic medicine}, volume = {13}, number = {6}, pages = {2793-2800}, pmid = {28587343}, issn = {1792-0981}, abstract = {Atrophic gastritis is considered to be an antecedent to intestinal metaplasia and gastric cancer. A previous study identified that Helicobacter pylori was absent at the severe atrophic gastritis stage, and alterations in the gastric microbial composition resembled those in gastric cancer. To explore the role of the bacteria absence of H. pylori in gastric carcinogenesis, in the current study, we compared the microbiota of clinically collected H. pylori-free gastric fluids from 30 patients with non-atrophic gastritis (N) and 22 patients with severe atrophic gastritis (S). We estimated the bacterial loads in the N and S groups by colony counting in culture agar as well as by measuring the concentration of the extracted DNA. The results showed a significant increase in bacterial load in patients with atrophic gastritis in comparison to non-atrophic gastritis. Then, we analyzed the microbial communities of the gastric fluids from all 52 patients using high-throughput sequencing of 16S rRNA amplicons. The Chao 1, Shannon and Simpson diversity indexes demonstrated that the bacterial richness and diversity were not significantly different between the N and S groups. Moreover, principal component analysis illustrated that the microbiomes from the S group were more scattered. Microbiota composition analysis showed that the entire dataset was clustered into 27 phyla, 61 classes, 106 orders, 177 families, 292 genera and 121 species. At the genus level, only the abundance of Prevotella was significantly different between the N and S groups. Further analysis showed that all the higher taxonomic categories were significantly different between the N and S groups. To assess the effects of the metabolic products of Prevotella spp. on gastric cell physiology, we treated the human gastric epithelial cell line AGS with acetic acid and monitored nitric oxide (NO) production. The results showed that acetic acid at low concentrations (0.5 and 5 µM) significantly inhibited AGS cells to secrete NO compared to phosphate buffer saline-treated control cells. These results suggest that the microbiota in non-atrophic gastritis may influence gastric epithelial cell physiology.}, }
@article {pmid28578872, year = {2017}, author = {Pollet, RM and D'Agostino, EH and Walton, WG and Xu, Y and Little, MS and Biernat, KA and Pellock, SJ and Patterson, LM and Creekmore, BC and Isenberg, HN and Bahethi, RR and Bhatt, AP and Liu, J and Gharaibeh, RZ and Redinbo, MR}, title = {An Atlas of β-Glucuronidases in the Human Intestinal Microbiome.}, journal = {Structure (London, England : 1993)}, volume = {25}, number = {7}, pages = {967-977.e5}, pmid = {28578872}, issn = {1878-4186}, support = {P30 ES010126/ES/NIEHS NIH HHS/United States ; T32 GM008570/GM/NIGMS NIH HHS/United States ; R01 CA161879/CA/NCI NIH HHS/United States ; R01 HL094463/HL/NHLBI NIH HHS/United States ; R01 CA207416/CA/NCI NIH HHS/United States ; T32 DK007737/DK/NIDDK NIH HHS/United States ; U01 GM102137/GM/NIGMS NIH HHS/United States ; R01 CA098468/CA/NCI NIH HHS/United States ; }, mesh = {Bacterial Proteins/*chemistry/classification/genetics/metabolism ; *Gastrointestinal Microbiome ; Glucuronidase/*chemistry/classification/genetics/metabolism ; Humans ; }, abstract = {Microbiome-encoded β-glucuronidase (GUS) enzymes play important roles in human health by metabolizing drugs in the gastrointestinal (GI) tract. The numbers, types, and diversity of these proteins in the human GI microbiome, however, remain undefined. We present an atlas of GUS enzymes comprehensive for the Human Microbiome Project GI database. We identify 3,013 total and 279 unique microbiome-encoded GUS proteins clustered into six unique structural categories. We assign their taxonomy, assess cellular localization, reveal the inter-individual variability within the 139 individuals sampled, and discover 112 novel microbial GUS enzymes. A representative in vitro panel of the most common GUS proteins by read abundances highlights structural and functional variabilities within the family, including their differential processing of smaller glucuronides and larger carbohydrates. These data provide a sequencing-to-molecular roadmap for examining microbiome-encoded enzymes essential to human health.}, }
@article {pmid28578396, year = {2017}, author = {Daisley, BA and Trinder, M and McDowell, TW and Welle, H and Dube, JS and Ali, SN and Leong, HS and Sumarah, MW and Reid, G}, title = {Neonicotinoid-induced pathogen susceptibility is mitigated by Lactobacillus plantarum immune stimulation in a Drosophila melanogaster model.}, journal = {Scientific reports}, volume = {7}, number = {1}, pages = {2703}, pmid = {28578396}, issn = {2045-2322}, mesh = {Animals ; Animals, Genetically Modified ; Biomarkers ; Disease Models, Animal ; *Disease Susceptibility ; Drosophila melanogaster ; Gram-Positive Bacterial Infections/*immunology/*microbiology/mortality ; Host-Pathogen Interactions/*immunology ; Insecticides/*pharmacology/toxicity ; Lactobacillus plantarum/*immunology ; Neonicotinoids/*pharmacology/toxicity ; Nitro Compounds/*pharmacology/toxicity ; }, abstract = {Pesticides are used extensively in food production to maximize crop yields. However, neonicotinoid insecticides exert unintentional toxicity to honey bees (Apis mellifera) that may partially be associated with massive population declines referred to as colony collapse disorder. We hypothesized that imidacloprid (common neonicotinoid; IMI) exposure would make Drosophila melanogaster (an insect model for the honey bee) more susceptible to bacterial pathogens, heat stress, and intestinal dysbiosis. Our results suggested that the immune deficiency (Imd) pathway is necessary for D. melanogaster survival in response to IMI toxicity. IMI exposure induced alterations in the host-microbiota as noted by increased indigenous Acetobacter and Lactobacillus spp. Furthermore, sub-lethal exposure to IMI resulted in decreased D. melanogaster survival when simultaneously exposed to bacterial infection and heat stress (37 °C). This coincided with exacerbated increases in TotA and Dpt (Imd downstream pro-survival and antimicrobial genes, respectively) expression compared to controls. Supplementation of IMI-exposed D. melanogaster with Lactobacillus plantarum ATCC 14917 mitigated survival deficits following Serratia marcescens (bacterial pathogen) septic infection. These findings support the insidious toxicity of neonicotinoid pesticides and potential for probiotic lactobacilli to reduce IMI-induced susceptibility to infection.}, }
@article {pmid28572753, year = {2017}, author = {Brooks, JP and Buck, GA and Chen, G and Diao, L and Edwards, DJ and Fettweis, JM and Huzurbazar, S and Rakitin, A and Satten, GA and Smirnova, E and Waks, Z and Wright, ML and Yanover, C and Zhou, YH}, title = {Changes in vaginal community state types reflect major shifts in the microbiome.}, journal = {Microbial ecology in health and disease}, volume = {28}, number = {1}, pages = {1303265}, pmid = {28572753}, issn = {0891-060X}, abstract = {Background: Recent studies of various human microbiome habitats have revealed thousands of bacterial species and the existence of large variation in communities of microorganisms in the same habitats across individual human subjects. Previous efforts to summarize this diversity, notably in the human gut and vagina, have categorized microbiome profiles by clustering them into community state types (CSTs). The functional relevance of specific CSTs has not been established. Objective: We investigate whether CSTs can be used to assess dynamics in the microbiome. Design: We conduct a re-analysis of five sequencing-based microbiome surveys derived from vaginal samples with repeated measures. Results: We observe that detection of a CST transition is largely insensitive to choices in methods for normalization or clustering. We find that healthy subjects persist in a CST for two to three weeks or more on average, while those with evidence of dysbiosis tend to change more often. Changes in CST can be gradual or occur over less than one day. Upcoming CST changes and switches to high-risk CSTs can be predicted with high accuracy in certain scenarios. Finally, we observe that presence of Gardnerella vaginalis is a strong predictor of an upcoming CST change. Conclusion: Overall, our results show that the CST concept is useful for studying microbiome dynamics.}, }
@article {pmid28561849, year = {2017}, author = {Adnani, N and Rajski, SR and Bugni, TS}, title = {Symbiosis-inspired approaches to antibiotic discovery.}, journal = {Natural product reports}, volume = {34}, number = {7}, pages = {784-814}, pmid = {28561849}, issn = {1460-4752}, support = {R01 GM104192/GM/NIGMS NIH HHS/United States ; R01 GM107557/GM/NIGMS NIH HHS/United States ; U19 AI109673/AI/NIAID NIH HHS/United States ; U19 TW009872/TW/FIC NIH HHS/United States ; }, mesh = {Animals ; *Anti-Bacterial Agents ; Bacteria/metabolism ; Biological Evolution ; Fungi/physiology ; Humans ; Molecular Structure ; Multigene Family ; Plants/metabolism ; Symbiosis/*physiology ; }, abstract = {Covering: 2010 up to 2017Life on Earth is characterized by a remarkable abundance of symbiotic and highly refined relationships among life forms. Defined as any kind of close, long-term association between two organisms, symbioses can be mutualistic, commensalistic or parasitic. Historically speaking, selective pressures have shaped symbioses in which one organism (typically a bacterium or fungus) generates bioactive small molecules that impact the host (and possibly other symbionts); the symbiosis is driven fundamentally by the genetic machineries available to the small molecule producer. The human microbiome is now integral to the most recent chapter in animal-microbe symbiosis studies and plant-microbe symbioses have significantly advanced our understanding of natural products biosynthesis; this also is the case for studies of fungal-microbe symbioses. However, much less is known about microbe-microbe systems involving interspecies interactions. Microbe-derived small molecules (i.e. antibiotics and quorum sensing molecules, etc.) have been shown to regulate transcription in microbes within the same environmental niche, suggesting interspecies interactions whereas, intraspecies interactions, such as those that exploit autoinducing small molecules, also modulate gene expression based on environmental cues. We, and others, contend that symbioses provide almost unlimited opportunities for the discovery of new bioactive compounds whose activities and applications have been evolutionarily optimized. Particularly intriguing is the possibility that environmental effectors can guide laboratory expression of secondary metabolites from "orphan", or silent, biosynthetic gene clusters (BGCs). Notably, many of the studies summarized here result from advances in "omics" technologies and highlight how symbioses have given rise to new anti-bacterial and antifungal natural products now being discovered.}, }
@article {pmid28557822, year = {2017}, author = {de Clercq, NC and Frissen, MN and Groen, AK and Nieuwdorp, M}, title = {Gut Microbiota and the Gut-Brain Axis: New Insights in the Pathophysiology of Metabolic Syndrome.}, journal = {Psychosomatic medicine}, volume = {79}, number = {8}, pages = {874-879}, doi = {10.1097/PSY.0000000000000495}, pmid = {28557822}, issn = {1534-7796}, mesh = {Animals ; *Brain/metabolism ; *Gastrointestinal Microbiome ; Humans ; Metabolic Syndrome/immunology/*metabolism/microbiology ; *Signal Transduction ; }, abstract = {OBJECTIVE: Emerging preclinical evidence has shown that the bidirectional signaling between the gastrointestinal (GI) tract and the brain, the so-called gut-brain axis, plays an important role in both host metabolism and behavior. In this review, we discuss the potential mechanisms of the brain-gut axis in relation to the pathophysiology of metabolic syndrome.<br><br>METHODS: A selective literature review was conducted to evaluate GI and brain interactions.<br><br>RESULTS: Evidence suggests reduced microbial diversity in obesity and metabolic dysregulation. However, findings of microbiota composition in obese individuals are inconsistent, and the investigation of causality between gut microbiota and energy homeostasis is complex because multiple variables contribute to the gut microbiota composition. The microbial metabolites short chain fatty acids are found to exert numerous physiologic effects, including energy homeostasis through the regulation of GI hormones such as cholecystokinin, glucagon-like peptide 1, peptide tyrosine-tyrosine, and leptin. Preclinical studies show that modifying rodents' microbiota through fecal transplantation results in alterations of these GI hormones and subsequently an altered metabolism and behavior. However, whether and to what extent preclinical findings translate to human metabolism is unclear.<br><br>CONCLUSIONS: One of the major limitations and challenges in this field of research is interindividual variability of the microbiome. Future research needs to combine recent insights gained into tracking the dynamics of the microbiome as well as the metabolic responses. Furthermore, advanced mapping of the human microbiome is required to investigate the metabolic implications of the gut-brain axis to develop targeted interventions for obesity and metabolic syndrome.}, }
@article {pmid28554152, year = {2017}, author = {Bardele, CF and Schultheiß, S and Lynn, DH and Wright, AG and Dominguez-Bello, MG and Obispo, NE}, title = {Aviisotricha hoazini n. gen., n. sp., the Morphology and Molecular Phylogeny of an Anaerobic Ciliate from the Crop of the Hoatzin (Opisthocomus hoazin), the Cow Among the Birds.}, journal = {Protist}, volume = {168}, number = {3}, pages = {335-351}, doi = {10.1016/j.protis.2017.02.002}, pmid = {28554152}, issn = {1618-0941}, mesh = {Anaerobiosis ; Animals ; Birds/*parasitology/physiology ; Ciliophora/*classification/genetics/*physiology/ultrastructure ; Crop, Avian/parasitology/physiology ; Microscopy, Electron, Scanning ; Microscopy, Electron, Transmission ; Sequence Analysis, DNA ; *Symbiosis ; }, abstract = {The hoatzin is the only known avian species that has evolved a foregut fermentation system similar to that of ruminant animals. Due to the closeness of the bird's fermentation chamber, the crop, to the bird's beak it exudes an unpleasant odour; therefore, the hoatzin is called the "cow among the birds". In addition to Eubacteria and Archaea, responsible for digestion of the vegetation they consume, the bird's crop contains a holotrich ciliate, described here for the first time in detail. Cytological staining of this isotrichid-like ciliate with the Chatton-Lwoff and Protargol staining procedures, as well as SEM and TEM, justified the establishment of the new genus Aviisotricha n. gen. with its new type species Aviisotricha hoazini n. gen., n. sp.. Phylogenetic analyses of a portion of the small subunit rRNA gene supported the taxonomic placement of this new genus and species in the family Isotrichidae. Aviisotricha is compared with Balantidium, Dasytricha and Isotricha with special reference to their dorsal brushes, which show similarity to the paralabial organelle of the Entodiniomorphida. The possible phylogenetic origin of Aviisotricha is discussed and a taxonomic revision of the family Isotrichidae is given.}, }
@article {pmid28540051, year = {2017}, author = {Chanyi, RM and Craven, L and Harvey, B and Reid, G and Silverman, MJ and Burton, JP}, title = {Faecal microbiota transplantation: Where did it start? What have studies taught us? Where is it going?.}, journal = {SAGE open medicine}, volume = {5}, number = {}, pages = {2050312117708712}, pmid = {28540051}, issn = {2050-3121}, abstract = {The composition and activity of microorganisms in the gut, the microbiome, is emerging as an important factor to consider with regard to the treatment of many diseases. Dysbiosis of the normal community has been implicated in inflammatory bowel disease, Crohn's disease, diabetes and, most notoriously, Clostridium difficile infection. In Canada, the leading treatment strategy for recalcitrant C. difficile infection is to receive faecal material which by nature is filled with microorganisms and their metabolites, from a healthy individual, known as a faecal microbiota transplantation. This influx of bacteria into the gut helps to restore the microbiota to a healthy state, preventing C. difficile from causing further disease. Much of what is known with respect to the microbiota and faecal microbiota transplantation comes from animal studies simulating the human disease. Although these models allow researchers to perform studies that would be difficult in humans, they do not always recapitulate the human microbiome. This makes the translation of these results to humans somewhat questionable. The purpose of this review is to analyse these animal models and discuss the advantages and the disadvantages of them in relation to human translation. By understanding some of the limitation of animal models, we will be better able to design and perform experiments of most relevance to human applications.}, }
@article {pmid28513546, year = {2017}, author = {Clark, AK and Haas, KN and Sivamani, RK}, title = {Edible Plants and Their Influence on the Gut Microbiome and Acne.}, journal = {International journal of molecular sciences}, volume = {18}, number = {5}, pages = {}, pmid = {28513546}, issn = {1422-0067}, support = {TL1 TR001861/TR/NCATS NIH HHS/United States ; UL1 TR001860/TR/NCATS NIH HHS/United States ; }, mesh = {Acne Vulgaris/*etiology/metabolism/prevention &amp; control/therapy ; *Dietary Supplements ; *Gastrointestinal Microbiome ; Humans ; *Plants, Edible ; Probiotics ; Skin/microbiology ; Skin Physiological Phenomena ; }, abstract = {Acne vulgaris affects most people at some point in their lives. Due to unclear etiology, likely with multiple factors, targeted and low-risk treatments have yet to be developed. In this review, we explore the multiple causes of acne and how plant-based foods and supplements can control these. The proposed causative factors include insulin resistance, sex hormone imbalances, inflammation and microbial dysbiosis. There is an emerging body of work on the human gut microbiome and how it mediates feedback between the foods we eat and our bodies. The gut microbiome is also an important mediator of inflammation in the gut and systemically. A low-glycemic load diet, one rich in plant fibers and low in processed foods, has been linked to an improvement in acne, possibly through gut changes or attenuation of insulin levels. Though there is much interest in the human microbiome, there is much more unknown, especially along the gut-skin axis. Collectively, the evidence suggests that approaches such as plant-based foods and supplements may be a viable alternative to the current first line standard of care for moderate acne, which typically includes antibiotics. Though patient compliance with major dietary changes is likely much lower than with medications, it is a treatment avenue that warrants further study and development.}, }
@article {pmid28507982, year = {2017}, author = {Martino, JV and Van Limbergen, J and Cahill, LE}, title = {The Role of Carrageenan and Carboxymethylcellulose in the Development of Intestinal Inflammation.}, journal = {Frontiers in pediatrics}, volume = {5}, number = {}, pages = {96}, pmid = {28507982}, issn = {2296-2360}, abstract = {Although the exact pathophysiology remains unknown, the development of inflammatory bowel disease (IBD) is influenced by the interplay between genetics, the immune system, and environmental factors such as diet. The commonly used food additives, carrageenan and carboxymethylcellulose (CMC), are used to develop intestinal inflammation in animal models. These food additives are excluded from current dietary approaches to induce disease remission in Crohn's disease such as exclusive enteral nutrition (EEN) using a polymeric formula. By reviewing the existing scientific literature, this review aims to discuss the role that carrageenan and CMC may play in the development of IBD. Animal studies consistently report that carrageenan and CMC induce histopathological features that are typical of IBD while altering the microbiome, disrupting the intestinal epithelial barrier, inhibiting proteins that provide protection against microorganisms, and stimulating the elaboration of pro-inflammatory cytokines. Similar trials directly assessing the influence of carrageenan and CMC in humans are of course unethical to conduct, but recent studies of human epithelial cells and the human microbiome support the findings from animal studies. Carrageenan and CMC may trigger or magnify an inflammatory response in the human intestine but are unlikely to be identified as the sole environmental factor involved in the development of IBD or in disease recurrence after treatment. However, the widespread use of carrageenan and CMC in foods consumed by the pediatric population in a "Western" diet is on the rise alongside a corresponding increase in IBD incidence, and questions are being raised about the safety of frequent usage of these food additives. Therefore, further research is warranted to elucidate the role of carrageenan and CMC in intestinal inflammation, which may help identify novel nutritional strategies that hinder the development of the disease or prevent disease relapse post-EEN treatment.}, }
@article {pmid28506279, year = {2017}, author = {Rath, S and Heidrich, B and Pieper, DH and Vital, M}, title = {Uncovering the trimethylamine-producing bacteria of the human gut microbiota.}, journal = {Microbiome}, volume = {5}, number = {1}, pages = {54}, pmid = {28506279}, issn = {2049-2618}, mesh = {Bacteria/*classification/enzymology/isolation &amp; purification/metabolism ; Bacterial Proteins/genetics ; Biosynthetic Pathways ; Feces/microbiology ; *Gastrointestinal Microbiome ; Humans ; Metagenomics/*methods ; Methylamines/*metabolism ; Multilocus Sequence Typing ; Phylogeny ; Sequence Analysis, DNA/methods ; }, abstract = {BACKGROUND: Trimethylamine (TMA), produced by the gut microbiota from dietary quaternary amines (mainly choline and carnitine), is associated with atherosclerosis and severe cardiovascular disease. Currently, little information on the composition of TMA producers in the gut is available due to their low abundance and the requirement of specific functional-based detection methods as many taxa show disparate abilities to produce that compound.<br><br>RESULTS: In order to examine the TMA-forming potential of microbial communities, we established databases for the key genes of the main TMA-synthesis pathways, encoding choline TMA-lyase (cutC) and carnitine oxygenase (cntA), using a multi-level screening approach on 67,134 genomes revealing 1107 and 6738 candidates to exhibit cutC and cntA, respectively. Gene-targeted assays enumerating the TMA-producing community by quantitative PCR and characterizing its composition via Illumina sequencing were developed and applied on human fecal samples (n&#x2009;=&#x2009;50) where all samples contained potential&#xa0;TMA producers (cutC was detected in all individuals, whereas only 26% harbored cntA) constituting, however, only a minor part of the total community (below 1% in most samples). Obtained cutC amplicons were associated with various taxa, in particular with Clostridium XIVa strains and Eubacterium sp. strain AB3007, though a bulk of sequences displayed low nucleotide identities to references (average 86%&#x2009;&#xb1;&#x2009;7%) indicating that key human TMA producers are yet to be isolated. Co-occurrence analysis revealed specific groups governing the community structure of cutC-exhibiting taxa across samples. CntA amplicons displayed high identities (~99%) to Gammaproteobacteria-derived references, primarily from Escherichia coli. Metagenomic analysis of samples provided by the Human Microbiome Project (n&#x2009;=&#x2009;154) confirmed the abundance patterns as well as overall taxonomic compositions obtained with our assays, though at much lower resolution, whereas 16S ribosomal RNA gene sequence analysis could not adequately uncover the TMA-producing potential.<br><br>CONCLUSIONS: In this study, we developed a diagnostic framework that enabled the quantification and comprehensive characterization of the TMA-producing potential in human fecal samples. The key players were identified, and together with predictions on their environmental niches using functional genomics on most closely related reference strains, we provide crucial information for the development of specific treatment strategies to restrain TMA producers and limit their proliferation.}, }
@article {pmid28505251, year = {2017}, author = {Xiao, J and Cao, H and Chen, J}, title = {False discovery rate control incorporating phylogenetic tree increases detection power in microbiome-wide multiple testing.}, journal = {Bioinformatics (Oxford, England)}, volume = {33}, number = {18}, pages = {2873-2881}, doi = {10.1093/bioinformatics/btx311}, pmid = {28505251}, issn = {1367-4811}, mesh = {Bacteria/*genetics ; Genomics/methods ; High-Throughput Nucleotide Sequencing/*methods ; Humans ; Microbiota/*genetics ; *Phylogeny ; Polymorphism, Genetic ; Sequence Analysis, DNA/methods ; *Software ; }, abstract = {MOTIVATION: Next generation sequencing technologies have enabled the study of the human microbiome through direct sequencing of microbial DNA, resulting in an enormous amount of microbiome sequencing data. One unique characteristic of microbiome data is the phylogenetic tree that relates all the bacterial species. Closely related bacterial species have a tendency to exhibit a similar relationship with the environment or disease. Thus, incorporating the phylogenetic tree information can potentially improve the detection power for microbiome-wide association studies, where hundreds or thousands of tests are conducted simultaneously to identify bacterial species associated with a phenotype of interest. Despite much progress in multiple testing procedures such as false discovery rate (FDR) control, methods that take into account the phylogenetic tree are largely limited.<br><br>RESULTS: We propose a new FDR control procedure that incorporates the prior structure information and apply it to microbiome data. The proposed procedure is based on a hierarchical model, where a structure-based prior distribution is designed to utilize the phylogenetic tree. By borrowing information from neighboring bacterial species, we are able to improve the statistical power of detecting associated bacterial species while controlling the FDR at desired levels. When the phylogenetic tree is mis-specified or non-informative, our procedure achieves a similar power as traditional procedures that do not take into account the tree structure. We demonstrate the performance of our method through extensive simulations and real microbiome datasets. We identified far more alcohol-drinking associated bacterial species than traditional methods.<br><br>R package StructFDR is available from CRAN.<br><br>CONTACT: chen.jun2@mayo.edu.<br><br>SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.}, }
@article {pmid28503170, year = {2017}, author = {Trinder, M and Daisley, BA and Dube, JS and Reid, G}, title = {Drosophila melanogaster as a High-Throughput Model for Host-Microbiota Interactions.}, journal = {Frontiers in microbiology}, volume = {8}, number = {}, pages = {751}, pmid = {28503170}, issn = {1664-302X}, abstract = {Microbiota research often assumes that differences in abundance and identity of microorganisms have unique influences on host physiology. To test this concept mechanistically, germ-free mice are colonized with microbial communities to assess causation. Due to the cost, infrastructure challenges, and time-consuming nature of germ-free mouse models, an alternative approach is needed to investigate host-microbial interactions. Drosophila melanogaster (fruit flies) can be used as a high throughput in vivo screening model of host-microbiome interactions as they are affordable, convenient, and replicable. D. melanogaster were essential in discovering components of the innate immune response to pathogens. However, axenic D. melanogaster can easily be generated for microbiome studies without the need for ethical considerations. The simplified microbiota structure enables researchers to evaluate permutations of how each microbial species within the microbiota contribute to host phenotypes of interest. This enables the possibility of thorough strain-level analysis of host and microbial properties relevant to physiological outcomes. Moreover, a wide range of mutant D. melanogaster strains can be affordably obtained from public stock centers. Given this, D. melanogaster can be used to identify candidate mechanisms of host-microbe symbioses relevant to pathogen exclusion, innate immunity modulation, diet, xenobiotics, and probiotic/prebiotic properties in a high throughput manner. This perspective comments on the most promising areas of microbiota research that could immediately benefit from using the D. melanogaster model.}, }
@article {pmid28492988, year = {2017}, author = {Brinkac, L and Voorhies, A and Gomez, A and Nelson, KE}, title = {The Threat of Antimicrobial Resistance on the Human Microbiome.}, journal = {Microbial ecology}, volume = {74}, number = {4}, pages = {1001-1008}, pmid = {28492988}, issn = {1432-184X}, support = {U19 AI110819/AI/NIAID NIH HHS/United States ; }, mesh = {Anti-Infective Agents/*pharmacology ; *Drug Resistance, Microbial ; Humans ; Microbiota/*drug effects ; }, abstract = {Ubiquitous in nature, antimicrobial resistance (AMR) has existed long before the golden age of antimicrobials. While antimicrobial agents are beneficial to combat infection, their widespread use contributes to the increase in and emergence of novel resistant microbes in virtually all environmental niches. The human microbiome is an important reservoir of AMR with initial exposure occurring in early life. Once seeded with AMR, commensal organisms may be key contributors to the dissemination of resistance due to the interconnectedness of microbial communities. When acquired by pathogens however, AMR becomes a serious public health threat worldwide. Our ability to combat the threat of emerging resistance relies on accurate AMR detection methods and the development of therapeutics that function despite the presence of antimicrobial resistance.}, }
@article {pmid28484044, year = {2017}, author = {Adebali, O and Petukh, MG and Reznik, AO and Tishkov, AV and Upadhyay, AA and Zhulin, IB}, title = {Class III Histidine Kinases: a Recently Accessorized Kinase Domain in Putative Modulators of Type IV Pilus-Based Motility.}, journal = {Journal of bacteriology}, volume = {199}, number = {18}, pages = {}, pmid = {28484044}, issn = {1098-5530}, support = {R01 DE024463/DE/NIDCR NIH HHS/United States ; R01 GM072285/GM/NIGMS NIH HHS/United States ; }, mesh = {Computational Biology ; Histidine Kinase/genetics/*metabolism ; *Locomotion ; Phylogeny ; Protein Domains ; Sequence Homology, Amino Acid ; *Signal Transduction ; Type IV Secretion Systems/*metabolism ; }, abstract = {Histidine kinases are key components of regulatory systems that enable bacteria to respond to environmental changes. Two major classes of histidine kinases are recognized on the basis of their modular design: classical (HKI) and chemotaxis specific (HKII). Recently, a new type of histidine kinase that appeared to have features of both HKIs and HKIIs was identified and termed HKIII; however, the details of HKIII's relationship to other two classes of histidine kinases, their function, and evolutionary history remain unknown. Here, we carried out genomic, phylogenetic, and protein sequence analyses that allowed us to reveal the unusual evolutionary history of this protein family, formalize its distinctive features, and propose its putative function. HKIIIs are characterized by the presence of sensory domains and the lack of a dimerization domain, which is typically present in all histidine kinases. In addition to a single-domain response regulator, HKIII signal transduction systems utilize CheX phosphatase and, in many instances, an unorthodox soluble chemoreceptor that are usual components of chemotaxis signal transduction systems. However, many HKIII genes are found in genomes completely lacking chemotaxis genes, thus decoupling their function from chemotaxis. By contrast, all HKIII-containing genomes also contain pilT, a marker gene for bacterial type IV pilus-based motility, whose regulation is proposed as a putative function for HKIII. These signal transduction systems have a narrow phyletic distribution but are present in many emerging and opportunistic pathogens, thus offering an attractive potential target for future antimicrobial drug design.IMPORTANCE Bacteria adapt to their environment and their hosts by detecting signals and regulating their cellular functions accordingly. Here, we describe a largely unexplored family of signal transduction histidine kinases, called HKIII, that have a unique modular design. While they are currently identified in a relatively short list of bacterial species, this list contains many emerging pathogens. We show that HKIIIs likely control bacterial motility across solid surfaces, which is a key virulence factor in many bacteria, including those causing severe infections. Full understanding of this putative function may help in designing effective drugs against pathogens that will not affect the majority of the beneficial human microbiome.}, }
@article {pmid28480145, year = {2017}, author = {Santiago-Rodriguez, TM and Narganes-Storde, Y and Chanlatte-Baik, L and Toranzos, GA and Cano, RJ}, title = {Insights of the dental calculi microbiome of pre-Columbian inhabitants from Puerto Rico.}, journal = {PeerJ}, volume = {5}, number = {}, pages = {e3277}, pmid = {28480145}, issn = {2167-8359}, abstract = {BACKGROUND: The study of ancient microorganisms in mineralized dental plaque or calculi is providing insights into microbial evolution, as well as lifestyles and disease states of extinct cultures; yet, little is still known about the oral microbial community structure and function of pre-Columbian Caribbean cultures. In the present study, we investigated the dental calculi microbiome and predicted function of one of these cultures, known as the Saladoid. The Saladoids were horticulturalists that emphasized root-crop production. Fruits, as well as small marine and terrestrial animals were also part of the Saladoid diet.<br><br>METHODS: Dental calculi samples were recovered from the archaeological site of Sorc&#xe9;, in the municipal island of Vieques, Puerto Rico, characterized using 16S rRNA gene high-throughput sequencing, and compared to the microbiome of previously characterized coprolites of the same culture, as well modern plaque, saliva and stool microbiomes available from the Human Microbiome Project.<br><br>RESULTS: Actinobacteria, Proteobacteria and Firmicutes comprised the majority of the Saladoid dental calculi microbiome. The Saladoid dental calculi microbiome was distinct when compared to those of modern saliva and dental plaque, but showed the presence of common inhabitants of modern oral cavities including Streptococcus sp., Veillonella dispar and Rothia mucilaginosa. Cell motility, signal transduction and biosynthesis of other secondary metabolites may be unique features of the Saladoid microbiome.<br><br>DISCUSSION: Results suggest that the Saladoid dental calculi microbiome structure and function may possibly reflect a horticulturalist lifestyle and distinct dietary habits. Results also open the opportunity to further elucidate oral disease states in extinct Caribbean cultures and extinct indigenous cultures with similar lifestyles.}, }
@article {pmid28476139, year = {2017}, author = {Kim, D and Hofstaedter, CE and Zhao, C and Mattei, L and Tanes, C and Clarke, E and Lauder, A and Sherrill-Mix, S and Chehoud, C and Kelsen, J and Conrad, M and Collman, RG and Baldassano, R and Bushman, FD and Bittinger, K}, title = {Optimizing methods and dodging pitfalls in microbiome research.}, journal = {Microbiome}, volume = {5}, number = {1}, pages = {52}, pmid = {28476139}, issn = {2049-2618}, support = {P30 AI045008/AI/NIAID NIH HHS/United States ; R01 HL113252/HL/NHLBI NIH HHS/United States ; T32 AI007632/AI/NIAID NIH HHS/United States ; T32 DK101371/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Humans ; Metagenomics ; Microbiological Techniques/*methods/standards ; Microbiota ; Reproducibility of Results ; Research Design/*standards ; }, abstract = {Research on the human microbiome has yielded numerous insights into health and disease, but also has resulted in a wealth of experimental artifacts. Here, we present suggestions for optimizing experimental design and avoiding known pitfalls, organized in the typical order in which studies are carried out. We first review best practices in experimental design and introduce common confounders such as age, diet, antibiotic use, pet ownership, longitudinal instability, and microbial sharing during cohousing in animal studies. Typically, samples will need to be stored, so we provide data on best practices for several sample types. We then discuss design and analysis of positive and negative controls, which should always be run with experimental samples. We introduce a convenient set of non-biological DNA sequences that can be useful as positive controls for high-volume analysis. Careful analysis of negative and positive controls is particularly important in studies of samples with low microbial biomass, where contamination can comprise most or all of a sample. Lastly, we summarize approaches to enhancing experimental robustness by careful control of multiple comparisons and to comparing discovery and validation cohorts. We hope the experimental tactics summarized here will help researchers in this exciting field advance their studies efficiently while avoiding errors.}, }
@article {pmid28473000, year = {2017}, author = {Lee, STM and Kahn, SA and Delmont, TO and Shaiber, A and Esen, &#xd6;C and Hubert, NA and Morrison, HG and Antonopoulos, DA and Rubin, DT and Eren, AM}, title = {Tracking microbial colonization in fecal microbiota transplantation experiments via genome-resolved metagenomics.}, journal = {Microbiome}, volume = {5}, number = {1}, pages = {50}, pmid = {28473000}, issn = {2049-2618}, support = {P30 DK042086/DK/NIDDK NIH HHS/United States ; T32 EB009412/EB/NIBIB NIH HHS/United States ; }, mesh = {Adult ; Bacteria/classification/*growth &amp; development ; Clostridium Infections/microbiology/*therapy ; DNA, Bacterial/genetics ; Fecal Microbiota Transplantation/*methods ; Female ; Gastrointestinal Tract/*microbiology ; Humans ; Living Donors ; Male ; Metagenomics/*methods ; Phylogeny ; Sequence Analysis, DNA/methods ; Young Adult ; }, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) is an effective treatment for recurrent Clostridium difficile infection and shows promise for treating other medical conditions associated with intestinal dysbioses. However, we lack a sufficient understanding of which microbial populations successfully colonize the recipient gut, and the widely used approaches to study the microbial ecology of FMT experiments fail to provide enough resolution to identify populations that are likely responsible for FMT-derived benefits.<br><br>METHODS: We used shotgun metagenomics together with assembly and binning strategies to reconstruct metagenome-assembled genomes (MAGs) from fecal samples of a single FMT donor. We then used metagenomic mapping to track the occurrence and distribution patterns of donor MAGs in two FMT recipients.<br><br>RESULTS: Our analyses revealed that 22% of the 92 highly complete bacterial MAGs that we identified from the donor successfully colonized and remained abundant in two recipients for at least 8&#xa0;weeks. Most MAGs with a high colonization rate belonged to the order Bacteroidales. The vast majority of those that lacked evidence of colonization belonged to the order Clostridiales, and colonization success was negatively correlated with the number of genes related to sporulation. Our analysis of 151 publicly available gut metagenomes showed that the donor MAGs that colonized both recipients were prevalent, and the ones that colonized neither were rare across the participants of the Human Microbiome Project. Although our dataset showed a link between taxonomy and the colonization ability of a given MAG, we also identified MAGs that belong to the same taxon with different colonization properties, highlighting the importance of an appropriate level of resolution to explore the functional basis of colonization and to identify targets for cultivation, hypothesis generation, and testing in model systems.<br><br>CONCLUSIONS: The analytical strategy adopted in our study can provide genomic insights into bacterial populations that may be critical to the efficacy of FMT due to their success in gut colonization and metabolic properties, and guide cultivation efforts to investigate mechanistic underpinnings of this procedure beyond associations.}, }
@article {pmid28469609, year = {2017}, author = {Sankaran-Walters, S and Hart, R and Dills, C}, title = {Guardians of the Gut: Enteric Defensins.}, journal = {Frontiers in microbiology}, volume = {8}, number = {}, pages = {647}, pmid = {28469609}, issn = {1664-302X}, support = {R21 HL126562/HL/NHLBI NIH HHS/United States ; }, abstract = {Enteric defensins likely play a key role in the management of the human microbiome throughout development. The functional and mechanistic diversity of defensins is much greater than was initially thought. Defensin expression and overall Paneth cell physiology likely plays a key role in the development of colitis and other inflammatory or dysbiotic diseases of the gut. As our understanding of enteric defensins grows, their potential as tools of clinical intervention becomes more apparent. In this review, we focus on the function and activity of Paneth Cell defensins and highlight their role in disease.}, }
@article {pmid28462050, year = {2017}, author = {Walsh, CJ and Guinane, CM and O' Toole, PW and Cotter, PD}, title = {A Profile Hidden Markov Model to investigate the distribution and frequency of LanB-encoding lantibiotic modification genes in the human oral and gut microbiome.}, journal = {PeerJ}, volume = {5}, number = {}, pages = {e3254}, pmid = {28462050}, issn = {2167-8359}, abstract = {BACKGROUND: The human microbiota plays a key role in health and disease, and bacteriocins, which are small, bacterially produced, antimicrobial peptides, are likely to have an important function in the stability and dynamics of this community. Here we examined the density and distribution of the subclass I lantibiotic modification protein, LanB, in human oral and stool microbiome datasets using a specially constructed profile Hidden Markov Model (HMM).<br><br>METHODS: The model was validated by correctly identifying known lanB genes in the genomes of known bacteriocin producers more effectively than other methods, while being sensitive enough to differentiate between different subclasses of lantibiotic modification proteins. This approach was compared with two existing methods to screen both genomic and metagenomic datasets obtained from the Human Microbiome Project (HMP).<br><br>RESULTS: Of the methods evaluated, the new profile HMM identified the greatest number of putative LanB proteins in the stool and oral metagenome data while BlastP identified the fewest. In addition, the model identified more LanB proteins than a pre-existing Pfam lanthionine dehydratase model. Searching the gastrointestinal tract subset of the HMP reference genome database with the new HMM identified seven putative subclass I lantibiotic producers, including two members of the Coprobacillus genus.<br><br>CONCLUSIONS: These findings establish custom profile HMMs as a potentially powerful tool in the search for novel bioactive producers with the power to benefit human health, and reinforce the repertoire of apparent bacteriocin-encoding gene clusters that may have been overlooked by culture-dependent mining efforts to date.}, }
@article {pmid28448493, year = {2017}, author = {Fisher, CK and Mora, T and Walczak, AM}, title = {Variable habitat conditions drive species covariation in the human microbiota.}, journal = {PLoS computational biology}, volume = {13}, number = {4}, pages = {e1005435}, pmid = {28448493}, issn = {1553-7358}, mesh = {Computational Biology ; *Ecosystem ; Humans ; Microbiota/*genetics/*physiology ; Models, Biological ; Species Specificity ; }, abstract = {Two species with similar resource requirements respond in a characteristic way to variations in their habitat-their abundances rise and fall in concert. We use this idea to learn how bacterial populations in the microbiota respond to habitat conditions that vary from person-to-person across the human population. Our mathematical framework shows that habitat fluctuations are sufficient for explaining intra-bodysite correlations in relative species abundances from the Human Microbiome Project. We explicitly show that the relative abundances of closely related species are positively correlated and can be predicted from taxonomic relationships. We identify a small set of functional pathways related to metabolism and maintenance of the cell wall that form the basis of a common resource sharing niche space of the human microbiota.}, }
@article {pmid28437450, year = {2017}, author = {Cai, Y and Zheng, W and Yao, J and Yang, Y and Mai, V and Mao, Q and Sun, Y}, title = {ESPRIT-Forest: Parallel clustering of massive amplicon sequence data in subquadratic time.}, journal = {PLoS computational biology}, volume = {13}, number = {4}, pages = {e1005518}, pmid = {28437450}, issn = {1553-7358}, support = {R01 AI125982/AI/NIAID NIH HHS/United States ; }, mesh = {*Algorithms ; *Cluster Analysis ; Computational Biology ; Databases, Genetic ; Humans ; Microbiota/genetics ; RNA, Ribosomal, 16S/genetics ; Sequence Alignment/*methods ; Sequence Analysis, RNA/*methods ; }, abstract = {The rapid development of sequencing technology has led to an explosive accumulation of genomic sequence data. Clustering is often the first step to perform in sequence analysis, and hierarchical clustering is one of the most commonly used approaches for this purpose. However, it is currently computationally expensive to perform hierarchical clustering of extremely large sequence datasets due to its quadratic time and space complexities. In this paper we developed a new algorithm called ESPRIT-Forest for parallel hierarchical clustering of sequences. The algorithm achieves subquadratic time and space complexity and maintains a high clustering accuracy comparable to the standard method. The basic idea is to organize sequences into a pseudo-metric based partitioning tree for sub-linear time searching of nearest neighbors, and then use a new multiple-pair merging criterion to construct clusters in parallel using multiple threads. The new algorithm was tested on the human microbiome project (HMP) dataset, currently one of the largest published microbial 16S rRNA sequence dataset. Our experiment demonstrated that with the power of parallel computing it is now compu- tationally feasible to perform hierarchical clustering analysis of tens of millions of sequences. The software is available at http://www.acsu.buffalo.edu/∼yijunsun/lab/ESPRIT-Forest.html.}, }
@article {pmid28435844, year = {2016}, author = {Stanley, N and Shai, S and Taylor, D and Mucha, PJ}, title = {Clustering network layers with the strata multilayer stochastic block model.}, journal = {IEEE transactions on network science and engineering}, volume = {3}, number = {2}, pages = {95-105}, pmid = {28435844}, issn = {2327-4697}, support = {R01 HD075712/HD/NICHD NIH HHS/United States ; T32 CA201159/CA/NCI NIH HHS/United States ; T32 GM067553/GM/NIGMS NIH HHS/United States ; }, abstract = {Multilayer networks are a useful data structure for simultaneously capturing multiple types of relationships between a set of nodes. In such networks, each relational definition gives rise to a layer. While each layer provides its own set of information, community structure across layers can be collectively utilized to discover and quantify underlying relational patterns between nodes. To concisely extract information from a multilayer network, we propose to identify and combine sets of layers with meaningful similarities in community structure. In this paper, we describe the "strata multilayer stochastic block model" (sMLSBM), a probabilistic model for multilayer community structure. The central extension of the model is that there exist groups of layers, called "strata", which are defined such that all layers in a given stratum have community structure described by a common stochastic block model (SBM). That is, layers in a stratum exhibit similar node-to-community assignments and SBM probability parameters. Fitting the sMLSBM to a multilayer network provides a joint clustering that yields node-to-community and layer-to-stratum assignments, which cooperatively aid one another during inference. We describe an algorithm for separating layers into their appropriate strata and an inference technique for estimating the SBM parameters for each stratum. We demonstrate our method using synthetic networks and a multilayer network inferred from data collected in the Human Microbiome Project.}, }
@article {pmid28434779, year = {2017}, author = {Lomholt, HB and Scholz, CFP and Brüggemann, H and Tettelin, H and Kilian, M}, title = {A comparative study of Cutibacterium (Propionibacterium) acnes clones from acne patients and healthy controls.}, journal = {Anaerobe}, volume = {47}, number = {}, pages = {57-63}, doi = {10.1016/j.anaerobe.2017.04.006}, pmid = {28434779}, issn = {1095-8274}, mesh = {Acne Vulgaris/*microbiology ; Adolescent ; Adult ; Female ; *Genetic Variation ; Genotype ; Gram-Positive Bacterial Infections/*microbiology ; *Healthy Volunteers ; Humans ; Male ; Multilocus Sequence Typing ; Propionibacterium acnes/*classification/genetics/*isolation &amp; purification ; Skin/microbiology ; Virulence Factors/analysis/genetics ; Whole Genome Sequencing ; Young Adult ; }, abstract = {BACKGROUND: Cutibacterium (Propionibacterium) acnes is assumed to play an important role in the pathogenesis of acne.<br><br>OBJECTIVES: To examine if clones with distinct virulence properties are associated with acne.<br><br>METHODS: Multiple C.&#xa0;acnes isolates from follicles and surface skin of patients with moderate to severe acne and healthy controls were characterized by multilocus sequence typing. To determine if CC18 isolates from acne patients differ from those of controls in the possession of virulence genes or lack of genes conducive to a harmonious coexistence the full genomes of dominating CC18 follicular clones from six patients and five controls were sequenced.<br><br>RESULTS: Individuals carried one to ten clones simultaneously. The dominating C.&#xa0;acnes clones in follicles from acne patients were exclusively from the phylogenetic clade I-1a and all belonged to clonal complex CC18 with the exception of one patient dominated by the worldwide-disseminated and often antibiotic resistant clone ST3. The clonal composition of healthy follicles showed a more heterogeneous pattern with follicles dominated by clones representing the phylogenetic clades I-1a, I-1b, I-2 and II. Comparison of follicular CC18 gene contents, allelic versions of putative virulence genes and their promoter regions, and 54 variable-length intragenic and inter-genic homopolymeric tracts showed extensive conservation and no difference associated with the clinical origin of isolates.<br><br>CONCLUSIONS: The study supports that C.&#xa0;acnes strains from clonal complex CC18 and the often antibiotic resistant clone ST3 are associated with acne and suggests that susceptibility of the host rather than differences within these clones may determine the clinical outcome of colonization.}, }
@article {pmid28419931, year = {2017}, author = {Pham, HL and Ho, CL and Wong, A and Lee, YS and Chang, MW}, title = {Applying the design-build-test paradigm in microbiome engineering.}, journal = {Current opinion in biotechnology}, volume = {48}, number = {}, pages = {85-93}, doi = {10.1016/j.copbio.2017.03.021}, pmid = {28419931}, issn = {1879-0429}, mesh = {Bacteria/classification/*genetics/isolation &amp; purification ; Bioengineering/*methods ; Humans ; Inflammation/genetics/microbiology/*therapy ; *Metagenome ; *Microbiota ; *Probiotics ; }, abstract = {The recently discovered roles of human microbiome in health and diseases have inspired research efforts across many disciplines to engineer microbiome for health benefits. In this review, we highlight recent progress in human microbiome research and how modifications to the microbiome could result in implications to human health. Furthermore, we discuss the application of a 'design-build-test' framework to expedite microbiome engineering efforts by reviewing current literature on three key aspects: design principles to engineer the human microbiome, methods to engineer microbiome with desired functions, and analytical techniques to examine complex microbiome samples.}, }
@article {pmid28405695, year = {2017}, author = {Salzberger, B and Lehnert, H and Mössner, J}, title = {[The human microbiome].}, journal = {Der Internist}, volume = {58}, number = {5}, pages = {427-428}, doi = {10.1007/s00108-017-0230-3}, pmid = {28405695}, issn = {1432-1289}, mesh = {Autoimmune Diseases/immunology/microbiology/physiopathology ; Biomedical Research ; Clostridium Infections/microbiology/therapy ; Energy Metabolism/immunology/physiology ; Fecal Microbiota Transplantation ; Feces/microbiology ; Feeding Behavior ; Humans ; Intestines/immunology/*microbiology ; Metabolic Diseases/microbiology/physiopathology ; Microbiota/genetics/immunology/*physiology ; }, }
@article {pmid28398290, year = {2017}, author = {Hahn, AS and Altman, T and Konwar, KM and Hanson, NW and Kim, D and Relman, DA and Dill, DL and Hallam, SJ}, title = {A geographically-diverse collection of 418 human gut microbiome pathway genome databases.}, journal = {Scientific data}, volume = {4}, number = {}, pages = {170035}, pmid = {28398290}, issn = {2052-4463}, support = {R01 GM099534/GM/NIGMS NIH HHS/United States ; T32 GM008412/GM/NIGMS NIH HHS/United States ; }, mesh = {Crohn Disease/microbiology ; *Databases, Genetic ; Diabetes Mellitus, Type 2/microbiology ; *Gastrointestinal Microbiome ; Geography, Medical ; Humans ; Inflammatory Bowel Diseases/microbiology ; *Metabolic Networks and Pathways ; Metagenome ; Metagenomics ; }, abstract = {Advances in high-throughput sequencing are reshaping how we perceive microbial communities inhabiting the human body, with implications for therapeutic interventions. Several large-scale datasets derived from hundreds of human microbiome samples sourced from multiple studies are now publicly available. However, idiosyncratic data processing methods between studies introduce systematic differences that confound comparative analyses. To overcome these challenges, we developed GutCyc, a compendium of environmental pathway genome databases (ePGDBs) constructed from 418 assembled human microbiome datasets using MetaPathways, enabling reproducible functional metagenomic annotation. We also generated metabolic network reconstructions for each metagenome using the Pathway Tools software, empowering researchers and clinicians interested in visualizing and interpreting metabolic pathways encoded by the human gut microbiome. For the first time, GutCyc provides consistent annotations and metabolic pathway predictions, making possible comparative community analyses between health and disease states in inflammatory bowel disease, Crohn's disease, and type 2 diabetes. GutCyc data products are searchable online, or may be downloaded and explored locally using MetaPathways and Pathway Tools.}, }
@article {pmid28391505, year = {2017}, author = {Somboonna, N and Wilantho, A and Srisuttiyakorn, C and Assawamakin, A and Tongsima, S}, title = {Bacterial communities on facial skin of teenage and elderly Thai females.}, journal = {Archives of microbiology}, volume = {199}, number = {7}, pages = {1035-1042}, doi = {10.1007/s00203-017-1375-0}, pmid = {28391505}, issn = {1432-072X}, support = {RSA58-80061//Thailand Research Fund/ ; }, mesh = {Acne Vulgaris/*microbiology ; Adult ; *Bacteria/classification/genetics/isolation &amp; purification ; Base Sequence ; Female ; Humans ; Microbiota/*genetics ; Middle Aged ; Phylogeny ; RNA, Ribosomal, 16S/genetics ; Skin/*microbiology ; Thailand ; Young Adult ; }, abstract = {The Human Microbiome Project was first established to understand the roles of human-associated microbes to human health and disease. This study presents preliminary findings of Thai female facial skin microbiome using three pooled samples from groups of skin microbiome profiles, namely (1) healthy and (2) acne-prone young adults (teenage.hea and teenage.acn) and (3) healthy elderly adults (elderly.hea) based on standard dermatological criteria. These samples were sequenced using 454-pyrosequencing targeting 16S rRNA (V3-V4 regions). Good's coverage index of greater than 92% shows sufficient sampling of our data for each group. Three unique OTUs for each microbiome profile (43, 258 and 59 for teenage.hea, teenage.acn and ederly.hea, respectively) were obtained with 134 shared OTUs among the three datasets. Based on Morisita-Horn similarity coefficient, age is the major factor that brings the community relationship factor closer. The comparison among the three datasets reveal majority of Gemmatimonadetes, Planctomycetes and Nitrospirae in the teenage.hea, whereas Firmicutes are more prevalent in teenage.acn and elderly.hea skin types. In addition, when comparing Thai facial microbial diversity with the 16S data from U.S. forehead female database, significant differences were found among orders of bacteria, pointing to possible differences in human ecto-flora.}, }
@article {pmid28390199, year = {2016}, author = {Kolip, D and Yılmaz, N and Gökkaya, B and Kulan, P and Kargul, B and MacDonald, KW and Cadieux, PA and Burton, JP and James, KM}, title = {Efficacy of Dentaq® Oral and ENT Health Probiotic Complex on Clinical Parameters of Gingivitis in Patients Undergoing Fixed Orthodontic Treatment: A Pilot Study.}, journal = {The Journal of clinical dentistry}, volume = {27}, number = {3}, pages = {66-70}, pmid = {28390199}, issn = {0895-8831}, mesh = {Adolescent ; Child ; Dental Plaque ; *Dental Plaque Index ; Female ; Gingivitis/*therapy ; Humans ; Male ; Periodontal Index ; Pilot Projects ; *Probiotics ; }, abstract = {OBJECTIVES: Probiotics act as a unique approach to maintaining oral health by supplementing the endogenous oral bacteria with additional naturally occurring beneficial microbes to provide defense against pathogens harmful to teeth and gingiva. The aim of this pilot study was to clinically evaluate the effects of probiotics on plaque accumulation and gingival inflammation in subjects with fixed orthodontics.<br><br>METHODS: The pilot study was comprised of 15 healthy patients, aged 11 to 18 years, undergoing fixed orthodontic treatment. Patients used an all-natural, dissolving lozenge containing six proprietary probiotic strains (Dentaq&#xae; Oral and ENT Health Probiotic Complex)for 28 days. Gingival Index (GI) according to L&#xf6;e-Silness and Plaque Index (PI) according to Quigley-Hein for all teeth were measured at baseline (Day Zero) and at the end of the probiotic regimen (Day 28).<br><br>RESULTS: The mean baseline GI and PI scores within each patient decreased by 28.4% and 35.8%, respectively, by Day 28. Patients reported decreased tooth and gingival pain, decreased oral bleeding, and increased motivation to maintain proper oral hygiene over the course of the study.<br><br>CONCLUSIONS: This pilot study provided preliminary support for the use of Dentaq Oral and ENT Health Probiotic Complex as a safe and effective natural health product for the reduction of plaque accumulation and gingival inflammation. The results demonstrate its potential therapeutic value and open the door for larger scale placebo-controlled clinical studies to verify these findings.}, }
@article {pmid28389564, year = {2017}, author = {Wilson, MR and Zha, L and Balskus, EP}, title = {Natural product discovery from the human microbiome.}, journal = {The Journal of biological chemistry}, volume = {292}, number = {21}, pages = {8546-8552}, pmid = {28389564}, issn = {1083-351X}, support = {R01 CA208834/CA/NCI NIH HHS/United States ; }, mesh = {Anti-Bacterial Agents/biosynthesis ; Antifungal Agents/metabolism ; Antineoplastic Agents/metabolism ; Gastrointestinal Microbiome/*physiology ; Humans ; Microbial Consortia/*physiology ; Peptide Biosynthesis, Nucleic Acid-Independent/physiology ; Peptides/metabolism ; Polyketides/metabolism ; }, abstract = {Human-associated microorganisms have the potential to biosynthesize numerous secondary metabolites that may mediate important host-microbe and microbe-microbe interactions. However, there is currently a limited understanding of microbiome-derived natural products. A variety of complementary discovery approaches have begun to illuminate this microbial "dark matter," which will in turn allow detailed mechanistic studies of the effects of these molecules on microbiome and host. Herein, we review recent efforts to uncover microbiome-derived natural products, describe the key approaches that were used to identify and characterize these metabolites, discuss potential functional roles of these molecules, and highlight challenges related to this emerging research area.}, }
@article {pmid28384336, year = {2017}, author = {Maritz, JM and Sullivan, SA and Prill, RJ and Aksoy, E and Scheid, P and Carlton, JM}, title = {Filthy lucre: A metagenomic pilot study of microbes found on circulating currency in New York City.}, journal = {PloS one}, volume = {12}, number = {4}, pages = {e0175527}, pmid = {28384336}, issn = {1932-6203}, mesh = {Bacteria/*isolation &amp; purification ; Humans ; *Metagenomics ; New York City ; Pilot Projects ; Surface Properties ; }, abstract = {BACKGROUND: Paper currency by its very nature is frequently transferred from one person to another and represents an important medium for human contact with-and potential exchange of-microbes. In this pilot study, we swabbed circulating $1 bills obtained from a New York City bank in February (Winter) and June (Summer) 2013 and used shotgun metagenomic sequencing to profile the communities found on their surface. Using basic culture conditions, we also tested whether viable microbes could be recovered from bills.<br><br>RESULTS: Shotgun metagenomics identified eukaryotes as the most abundant sequences on money, followed by bacteria, viruses and archaea. Eukaryotic assemblages were dominated by human, other metazoan and fungal taxa. The currency investigated harbored a diverse microbial population that was dominated by human skin and oral commensals, including Propionibacterium acnes, Staphylococcus epidermidis and Micrococcus luteus. Other taxa detected not associated with humans included Lactococcus lactis and Streptococcus thermophilus, microbes typically associated with dairy production and fermentation. Culturing results indicated that viable microbes can be isolated from paper currency.<br><br>CONCLUSIONS: We conducted the first metagenomic characterization of the surface of paper money in the United States, establishing a baseline for microbes found on $1 bills circulating in New York City. Our results suggest that money amalgamates DNA from sources inhabiting the human microbiome, food, and other environmental inputs, some of which can be recovered as viable organisms. These monetary communities may be maintained through contact with human skin, and DNA obtained from money may provide a record of human behavior and health. Understanding these microbial profiles is especially relevant to public health as money could potentially mediate interpersonal transfer of microbes.}, }
@article {pmid28383809, year = {2017}, author = {Wackett, LP}, title = {Web alert: Human microbiome: An annotated selection of World Wide Web sites relevant to the topics in environmental microbiology.}, journal = {Environmental microbiology}, volume = {19}, number = {4}, pages = {1687-1688}, doi = {10.1111/1462-2920.13738}, pmid = {28383809}, issn = {1462-2920}, }
@article {pmid28383789, year = {2017}, author = {Acharya, A and Chan, Y and Kheur, S and Kheur, M and Gopalakrishnan, D and Watt, RM and Mattheos, N}, title = {Salivary microbiome of an urban Indian cohort and patterns linked to subclinical inflammation.}, journal = {Oral diseases}, volume = {23}, number = {7}, pages = {926-940}, doi = {10.1111/odi.12676}, pmid = {28383789}, issn = {1601-0825}, mesh = {Adult ; Aged ; *Asymptomatic Diseases ; Female ; Humans ; India ; Inflammation/*microbiology ; Interleukin-1beta/metabolism ; Male ; *Microbiota ; Middle Aged ; Saliva/metabolism/*microbiology ; Urban Population ; }, abstract = {OBJECTIVE: To profile salivary microbiomes of an urban-living, healthy Indian cohort and explore associations with proinflammatory status.<br><br>METHODS: Fifty-one clinically healthy Indian subjects' salivary microbiomes were analyzed using 16S rRNA Illumina MiSeq sequencing. Community distribution was compared with salivary data from the Human Microbiome Project (HMP). Indian subjects were clustered using microbiome-based "partitioning along medoids" (PAM), and relationships of interleukin-1 beta levels with community composition were analyzed.<br><br>RESULTS: Indian subjects presented higher phylogenetic diversity than HMP. Several taxa associated with traditional societies gut microbiomes (Bacteroidales, Paraprevotellaceae, and Spirochaetaceae) were raised. Bifidobacteriaceae and Lactobacillaceae were approximately fourfold greater. A PAM cluster enriched in several Proteobacteria, Actinobacteria, and Bacilli taxa and having almost twofold higher Prevotella to Bacteroides ratio showed significant overrepresentation of subjects within the highest quartile of salivary interleukin-1 beta levels. Abiotrophia, Anaerobacillus, Micrococcus, Aggregatibacter, Halomonas, Propionivivrio, Paracoccus, Mannhemia, unclassified Bradyrhizobiaceae, and Caulobacteraceae were each significant indicators of presence in the highest interleukin-1 beta quartile. 2 OTUs representing Lactobacillus fermentum and Cardiobacterium hominis significantly correlated with interleukin-1 beta levels.<br><br>CONCLUSION: The salivary microbiome of this urban-dwelling Indian cohort differed significantly from that of a well-studied Western cohort. Specific community patterns were putatively associated with subclinical inflammation levels.}, }
@article {pmid28375407, year = {2017}, author = {Lacy, BE}, title = {Hot Topics in Primary Care: Role of the Microbiome in Disease: Implications for Treatment of Irritable Bowel Syndrome.}, journal = {The Journal of family practice}, volume = {66}, number = {4 Suppl}, pages = {S40-S45}, pmid = {28375407}, issn = {1533-7294}, mesh = {Anti-Bacterial Agents/*therapeutic use ; Education, Medical, Continuing ; Gastrointestinal Microbiome/*drug effects ; Humans ; Irritable Bowel Syndrome/*diagnosis/*drug therapy/microbiology/physiopathology ; *Practice Guidelines as Topic ; Primary Health Care/*standards ; Probiotics/*therapeutic use ; United States ; }, abstract = {Dietary and some other treatments for IBS are supported by a growing body of evidence, much of which comes from programs such as the Human Microbiome Project and Human Gut Microbiome Initiative, which were intended to identify and characterize microorganisms found in association with both healthy and diseased humans. These programs used state-of-the-art technology to characterize the human microbiome from multiple body sites. This evidence indicates that the gut microbiome plays an important role in IBS and some other gastrointestinal (GI) disorders.}, }
@article {pmid28374191, year = {2017}, author = {Gallego-Paez, LM and Bordone, MC and Leote, AC and Saraiva-Agostinho, N and Ascensão-Ferreira, M and Barbosa-Morais, NL}, title = {Alternative splicing: the pledge, the turn, and the prestige : The key role of alternative splicing in human biological systems.}, journal = {Human genetics}, volume = {136}, number = {9}, pages = {1015-1042}, pmid = {28374191}, issn = {1432-1203}, support = {Installation Grant (3057)//European Molecular Biology Organization/International ; Investigador FCT Starting Grant (IF/00595/2014)//Funda&#xe7;&#xe3;o para a Ci&#xea;ncia e a Tecnologia/International ; PhD fellowship (PD/BD/105854/2014)//Funda&#xe7;&#xe3;o para a Ci&#xea;ncia e a Tecnologia/International ; PhD fellowship (PD/BD/128283/2017)//Funda&#xe7;&#xe3;o para a Ci&#xea;ncia e a Tecnologia/International ; Women in Science Program (ERI/NCS/FLP/CDC.13.94)//United Nations Educational, Scientific and Cultural Organization/International ; Innovate Competition Award//Funda&#xe7;&#xe3;o AstraZeneca/International ; IMM/BPD/45-2016,LISBOA-01-0145-FEDER-007391//iMM/FCT/MEC/FEDER/International ; Start-up funds//Instituto de Medicina Molecular/International ; }, mesh = {*Alternative Splicing ; Humans ; Microbiota ; RNA, Messenger/*genetics/*metabolism ; }, abstract = {Alternative pre-mRNA splicing is a tightly controlled process conducted by the spliceosome, with the assistance of several regulators, resulting in the expression of different transcript isoforms from the same gene and increasing both transcriptome and proteome complexity. The differences between alternative isoforms may be subtle but enough to change the function or localization of the translated proteins. A fine control of the isoform balance is, therefore, needed throughout developmental stages and adult tissues or physiological conditions and it does not come as a surprise that several diseases are caused by its deregulation. In this review, we aim to bring the splicing machinery on stage and raise the curtain on its mechanisms and regulation throughout several systems and tissues of the human body, from neurodevelopment to the interactions with the human microbiome. We discuss, on one hand, the essential role of alternative splicing in assuring tissue function, diversity, and swiftness of response in these systems or tissues, and on the other hand, what goes wrong when its regulatory mechanisms fail. We also focus on the possibilities that splicing modulation therapies open for the future of personalized medicine, along with the leading techniques in this field. The final act of the spliceosome, however, is yet to be fully revealed, as more knowledge is needed regarding the complex regulatory network that coordinates alternative splicing and how its dysfunction leads to disease.}, }
@article {pmid28369713, year = {2017}, author = {Shi, P and Li, H}, title = {A model for paired-multinomial data and its application to analysis of data on a taxonomic tree.}, journal = {Biometrics}, volume = {73}, number = {4}, pages = {1266-1278}, pmid = {28369713}, issn = {1541-0420}, support = {R01 CA127334/CA/NCI NIH HHS/United States ; R01 GM097505/GM/NIGMS NIH HHS/United States ; }, mesh = {Bacteria/*classification ; Classification/*methods ; Computer Simulation ; Humans ; *Microbiota ; *Models, Statistical ; Respiratory Tract Infections/microbiology ; }, abstract = {In human microbiome studies, sequencing reads data are often summarized as counts of bacterial taxa at various taxonomic levels specified by a taxonomic tree. This article considers the problem of analyzing two repeated measurements of microbiome data from the same subjects. Such data are often collected to assess the change of microbial composition after certain treatment, or the difference in microbial compositions across body sites. Existing models for such count data are limited in modeling the covariance structure of the counts and in handling paired multinomial count data. A new probability distribution is proposed for paired-multinomial count data, which allows flexible covariance structure and can be used to model repeatedly measured multivariate count data. Based on this distribution, a test statistic is developed for testing the difference in compositions based on paired multinomial count data. The proposed test can be applied to the count data observed on a taxonomic tree in order to test difference in microbiome compositions and to identify the subtrees with different subcompositions. Simulation results indicate that proposed test has correct type 1 errors and increased power compared to some commonly used methods. An analysis of an upper respiratory tract microbiome data set is used to illustrate the proposed methods.}, }
@article {pmid28369698, year = {2017}, author = {Kwon, SJ and Kim, D and Lee, I and Kim, J and Dordick, JS}, title = {In vitro gene expression-coupled bacterial cell chip for screening species-specific antimicrobial enzymes.}, journal = {Biotechnology and bioengineering}, volume = {114}, number = {8}, pages = {1648-1657}, doi = {10.1002/bit.26300}, pmid = {28369698}, issn = {1097-0290}, mesh = {Bacterial Physiological Phenomena/*drug effects ; Bacterial Proteins/*administration &amp; dosage ; Biological Assay/*instrumentation ; Cell Survival/drug effects ; Drug Evaluation, Preclinical/*instrumentation ; Enzymes/*administration &amp; dosage ; Equipment Design ; Equipment Failure Analysis ; Gene Expression Profiling/*instrumentation ; Systems Integration ; Tissue Array Analysis/instrumentation ; }, abstract = {Targeting infectious bacterial pathogens is important for reducing the evolution of antibiotic-resistant bacteria and preserving the endogenous human microbiome. Cell lytic enzymes including bacteriophage endolysins, bacterial autolysins, and other bacteriolysins are useful antibiotic alternatives due to their exceptional target selectivity, which may be used to lysins rapidly kill target bacteria and their high specificity permit the normal commensal microflora to be left undisturbed. Genetic information of numerous lysins is currently available, but the identification of their antimicrobial function and specificity has been limited because most lysins are often poorly expressed and exhibit low solubilities. Here, we report the development of bacterial cell chip for rapidly accessing the function of diverse genes that are suggestive of encoding lysins. This approach can be used to evaluate rapidly the species-specific antimicrobial activity of diverse lysins synthesized from in vitro transcription and translation (TNT) of plasmid DNA. In addition, new potent lysins can be assessed that are not expressed in hosts and display low solubility. As a result of evaluating the species-specific antimicrobial function of 11 (un)known lysins with an in vitro TNT-coupled bacterial cell chip, a potent recombinant lysin against Staphylococcus strains, SA1, was identified. The SA1 was highly potent against not only S. aureus, but also both lysostaphin-resistant S. simulans and S. epidermidis cells. To this end, the SA1 may be applicable to treat both methicillin-resistant S. aureus (MRSA) and lysostaphin-resistant MRSA mutants. Biotechnol. Bioeng. 2017;114: 1648-1657. © 2017 Wiley Periodicals, Inc.}, }
@article {pmid28369261, year = {2017}, author = {Gorrie, CL and Mirceta, M and Wick, RR and Edwards, DJ and Thomson, NR and Strugnell, RA and Pratt, NF and Garlick, JS and Watson, KM and Pilcher, DV and McGloughlin, SA and Spelman, DW and Jenney, AWJ and Holt, KE}, title = {Gastrointestinal Carriage Is a Major Reservoir of Klebsiella pneumoniae Infection in Intensive Care Patients.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {65}, number = {2}, pages = {208-215}, pmid = {28369261}, issn = {1537-6591}, support = {/WT_/Wellcome Trust/United Kingdom ; }, mesh = {Adult ; Aged ; Anti-Bacterial Agents/pharmacology ; Carrier State/drug therapy/*epidemiology/microbiology ; Cohort Studies ; Cross Infection/epidemiology/*microbiology ; Female ; *Gastrointestinal Microbiome ; Gastrointestinal Tract/*microbiology ; Genetic Variation ; Humans ; *Intensive Care Units ; Klebsiella Infections/drug therapy/epidemiology/*microbiology/transmission ; Klebsiella pneumoniae/drug effects/genetics/*isolation &amp; purification ; Male ; Microbial Sensitivity Tests ; Middle Aged ; Pharynx/microbiology ; Prospective Studies ; Rectum/microbiology ; Risk Factors ; }, abstract = {BACKGROUND: Klebsiella pneumoniae is an opportunistic pathogen and leading cause of hospital-associated infections. Intensive care unit (ICU) patients are particularly at risk. Klebsiella pneumoniae is part of the healthy human microbiome, providing a potential reservoir for infection. However, the frequency of gut colonization and its contribution to infections are not well characterized.<br><br>METHODS: We conducted a 1-year prospective cohort study in which 498 ICU patients were screened for rectal and throat carriage of K. pneumoniae shortly after admission. Klebsiella pneumoniae isolated from screening swabs and clinical diagnostic samples were characterized using whole genome sequencing and combined with epidemiological data to identify likely transmission events.<br><br>RESULTS: Klebsiella pneumoniae carriage frequencies were estimated at 6% (95% confidence interval [CI], 3%-8%) among ICU patients admitted direct from the community, and 19% (95% CI, 14%-51%) among those with recent healthcare contact. Gut colonization on admission was significantly associated with subsequent infection (infection risk 16% vs 3%, odds ratio [OR] = 6.9, P < .001), and genome data indicated matching carriage and infection isolates in 80% of isolate pairs. Five likely transmission chains were identified, responsible for 12% of K. pneumoniae infections in ICU. In sum, 49% of K. pneumoniae infections were caused by the patients' own unique strain, and 48% of screened patients with infections were positive for prior colonization.<br><br>CONCLUSIONS: These data confirm K. pneumoniae colonization is a significant risk factor for infection in ICU, and indicate ~50% of K. pneumoniae infections result from patients' own microbiota. Screening for colonization on admission could limit risk of infection in the colonized patient and others.}, }
@article {pmid28360030, year = {2017}, author = {Young, VB}, title = {Old and new models for studying host-microbe interactions in health and disease: C. difficile as an example.}, journal = {American journal of physiology. Gastrointestinal and liver physiology}, volume = {312}, number = {6}, pages = {G623-G627}, doi = {10.1152/ajpgi.00341.2016}, pmid = {28360030}, issn = {1522-1547}, mesh = {Animals ; Clostridioides difficile/*pathogenicity ; Disease Models, Animal ; Enterocolitis, Pseudomembranous/*microbiology ; *Gastrointestinal Microbiome ; Gastrointestinal Tract/*microbiology ; Host-Pathogen Interactions ; Humans ; Organoids ; Symbiosis ; Tissue Culture Techniques ; }, abstract = {There has been an explosion of interest in studying the indigenous microbiota, which plays an important role in human health and disease. Traditionally, the study of microbes in relationship to human health involved consideration of individual microbial species that caused classical infectious diseases. With the interest in the human microbiome, an appreciation of the influence that complex communities of microbes can have on their environment has developed. When considering either individual pathogenic microbes or a symbiotic microbial community, researchers have employed a variety of model systems with which they can study the host-microbe interaction. With the use of studies of infections with the toxin-producing bacterium Clostridium difficile as a model for both a pathogen and beneficial bacterial communities as an example, this review will summarize and compare various model systems that can be used to gain insight into the host-microbe interaction.}, }
@article {pmid28357486, year = {2017}, author = {Tralau, T and Luch, A}, title = {The human microbiome, from Achilles armour to Nessus' shirt.}, journal = {Archives of toxicology}, volume = {91}, number = {7}, pages = {2699-2701}, doi = {10.1007/s00204-017-1951-8}, pmid = {28357486}, issn = {1432-0738}, mesh = {Animals ; Bacteria/*isolation &amp; purification ; Gastrointestinal Microbiome ; Humans ; *Microbiota ; Skin/microbiology ; }, }
@article {pmid28357466, year = {2017}, author = {Steinhagen, PR and Baumgart, DC}, title = {[Fundamentals of the microbiome].}, journal = {Der Internist}, volume = {58}, number = {5}, pages = {429-434}, pmid = {28357466}, issn = {1432-1289}, mesh = {Disease ; Humans ; *Microbial Consortia ; }, abstract = {Until the middle of the 20th century, clinical microbiology was limited to bacterial cultures enabling the detection of pathogenic microorganisms. Knowledge about the mutual relationship between humans and microorganisms has increased slowly. With the introduction of culture-independent analysis methods, comprehensive cataloging of the human microbiome was possible for the first time. Since then, compositional changes in relation to diseases have been studied. The goals of the Human Microbiome Project and MetaHIT include comparative studies of healthy and diseased individuals. Numerous libraries on time- and location-dependent changes of the microbiota composition in human diseases have been created. However, a mathematical correlation does not equal biological or medical relevance. Future research needs to validate the hypotheses generated in these studies in functional experiments and evaluate their true impact on clinical practice.}, }
@article {pmid28348497, year = {2017}, author = {Ertz-Archambault, N and Keim, P and Von Hoff, D}, title = {Microbiome and pancreatic cancer: A comprehensive topic review of literature.}, journal = {World journal of gastroenterology}, volume = {23}, number = {10}, pages = {1899-1908}, pmid = {28348497}, issn = {2219-2840}, mesh = {*Carcinogenesis ; Helicobacter pylori/*pathogenicity ; Humans ; *Microbiota ; Pancreas/*microbiology/pathology ; Pancreatic Neoplasms/*microbiology/pathology ; Risk Assessment ; Risk Factors ; }, abstract = {AIM: To review microbiome alterations associated with pancreatic cancer, its potential utility in diagnostics, risk assessment, and influence on disease outcomes.<br><br>METHODS: A comprehensive literature review was conducted by all-inclusive topic review from PubMed, MEDLINE, and Web of Science. The last search was performed in October 2016.<br><br>RESULTS: Diverse microbiome alterations exist among several body sites including oral, gut, and pancreatic tissue, in patients with pancreatic cancer compared to healthy populations.<br><br>CONCLUSION: Pilot study successes in non-invasive screening strategies warrant further investigation for future translational application in early diagnostics and to learn modifiable risk factors relevant to disease prevention. Pre-clinical investigations exist in other tumor types that suggest microbiome manipulation provides opportunity to favorably transform cancer response to existing treatment protocols and improve survival.}, }
@article {pmid28345793, year = {2017}, author = {Ehrmann, M and Kaiser, M}, title = {Small Molecules from Deep within the Gut.}, journal = {Chembiochem : a European journal of chemical biology}, volume = {18}, number = {11}, pages = {967-968}, doi = {10.1002/cbic.201700165}, pmid = {28345793}, issn = {1439-7633}, mesh = {Humans ; Metagenomics/methods ; Microbiota/*physiology ; Multigene Family ; Peptide Synthases/analysis/genetics ; Physiological Phenomena/*physiology ; Protease Inhibitors ; }, abstract = {Although the influence of the human microbiome on host functions is widely recognized, the underlying molecular mechanisms are still largely unknown. A recent study by the Fischbach group now provides an experimental workflow for characterizing and evaluating the impact of microbiome-derived small molecules on host physiology.}, }
@article {pmid28345059, year = {2017}, author = {Martí, JM and Martínez-Martínez, D and Rubio, T and Gracia, C and Peña, M and Latorre, A and Moya, A and P Garay, C}, title = {Health and Disease Imprinted in the Time Variability of the Human Microbiome.}, journal = {mSystems}, volume = {2}, number = {2}, pages = {}, pmid = {28345059}, issn = {2379-5077}, abstract = {The animal microbiota (including the human microbiota) plays an important role in keeping the physiological status of the host healthy. Research seeks greater insight into whether changes in the composition and function of the microbiota are associated with disease. We analyzed published 16S rRNA and shotgun metagenomic sequencing (SMS) data pertaining to the gut microbiotas of 99 subjects monitored over time. Temporal fluctuations in the microbial composition revealed significant differences due to factors such as dietary changes, antibiotic intake, age, and disease. This article shows that a fluctuation scaling law can describe the temporal changes in the gut microbiota. This law estimates the temporal variability of the microbial population and quantitatively characterizes the path toward disease via a noise-induced phase transition. Estimation of the systemic parameters may be of clinical utility in follow-up studies and have more general applications in fields where it is important to know whether a given community is stable or not. IMPORTANCE The human microbiota correlates closely with the health status of its host. This article analyzes the microbial composition of several subjects under different conditions over time spans that ranged from days to months. Using the Langevin equation as the basis of our mathematical framework to evaluate microbial temporal stability, we proved that stable microbiotas can be distinguished from unstable microbiotas. This initial step will help us to determine how temporal microbiota stability is related to a subject's health status and to develop a more comprehensive framework that will provide greater insight into this complex system.}, }
@article {pmid28333226, year = {2017}, author = {Rojo, D and Méndez-García, C and Raczkowska, BA and Bargiela, R and Moya, A and Ferrer, M and Barbas, C}, title = {Exploring the human microbiome from multiple perspectives: factors altering its composition and function.}, journal = {FEMS microbiology reviews}, volume = {41}, number = {4}, pages = {453-478}, pmid = {28333226}, issn = {1574-6976}, mesh = {*Biodiversity ; Humans ; *Metabolome ; Microbiota/*physiology ; }, abstract = {Our microbiota presents peculiarities and characteristics that may be altered by multiple factors. The degree and consequences of these alterations depend on the nature, strength and duration of the perturbations as well as the structure and stability of each microbiota. The aim of this review is to sketch a very broad picture of the factors commonly influencing different body sites, and which have been associated with alterations in the human microbiota in terms of composition and function. To do so, first, a graphical representation of bacterial, fungal and archaeal genera reveals possible associations among genera affected by different factors. Then, the revision of sequence-based predictions provides associations with functions that become part of the active metabolism. Finally, examination of microbial metabolite contents and fluxes reveals whether metabolic alterations are a reflection of the differences observed at the level of population structure, and in the last step, link microorganisms to functions under perturbations that differ in nature and aetiology. The utilisation of complementary technologies and methods, with a special focus on metabolomics research, is thoroughly discussed to obtain a global picture of microbiota composition and microbiome function and to convey the urgent need for the standardisation of protocols.}, }
@article {pmid28329759, year = {2017}, author = {Brito, IL and Yilmaz, S and Huang, K and Xu, L and Jupiter, SD and Jenkins, AP and Naisilisili, W and Tamminen, M and Smillie, CS and Wortman, JR and Birren, BW and Xavier, RJ and Blainey, PC and Singh, AK and Gevers, D and Alm, EJ}, title = {Corrigendum: Mobile genes in the human microbiome are structured from global to individual scales.}, journal = {Nature}, volume = {544}, number = {7648}, pages = {124}, pmid = {28329759}, issn = {1476-4687}, }
@article {pmid28286571, year = {2017}, author = {Shivaji, S}, title = {We are not alone: a case for the human microbiome in extra intestinal diseases.}, journal = {Gut pathogens}, volume = {9}, number = {}, pages = {13}, pmid = {28286571}, issn = {1757-4749}, abstract = {BACKGROUND: "Dysbiosis" in the gut microbiome has been implicated in auto-immune diseases, in inflammatory diseases, in some cancers and mental disorders. The challenge is to unravel the cellular and molecular basis of dysbiosis so as to understand the disease manifestation.<br><br>MAIN BODY: Next generation sequencing and genome enabled technologies have led to the establishment of the composition of gut microbiomes and established that "dysbiosis" is the cause of several diseases. In a few cases the cellular and molecular changes accompanying dysbiosis have been investigated and correlated with the disease. Gut microbiome studies have indicated that Christensenella minuta controls obesity in mice, Faecalibacterium prausnitzii protects mice against intestinal inflammation and Akkermansia muciniphila reverses obesity and insulin resistance by secreting endocannabinoids. In mice polysaccharide antigen A on the surface of Bacteroides fragilis, reduces inflammation. Such experiments provide the link between the gut microbiome and human health but implicating dysbiosis with extra-intestinal diseases like arthritis, muscular dystrophy, vaginosis, fibromyalgia, some cancers and mental disorders appears to be more challenging. The relevance of gut microbiome to the eye appears to be very remote. But considering that the eye is the site of inflammatory diseases like uveitis, scleritis, Mooren's corneal ulcer etc. it is possible that these diseases are also influenced by dysbiosis. In mice signals from the gut microbiota activate retina specific T cells that are involved in autoimmune uveitis. Such information would open up new strategies for therapy where the emphasis would be on restoring the diversity in the gut by antibiotic or specific drug use, specific microbe introduction, probiotic use and fecal transplant therapy. The ocular surface microbiome may also be responsible for eye diseases in man but such studies are lacking. Microbiome of the healthy cornea and conjunctiva have been identified. But whether the ocular microbiome exhibits dysbiosis with disease? Whether ocular microbiome is influenced by the gut microbiome? What mediates the cross-talk between the gut and ocular microbiomes? These are questions that need to be addressed to understand idiopathic infections of the eye.<br><br>CONCLUSIONS: Evaluating diseases remote from the gut would unfold the mysteries of the microbiome.}, }
@article {pmid28282257, year = {2018}, author = {Chuong, KH and Mack, DR and Stintzi, A and O'Doherty, KC}, title = {Human Microbiome and Learning Healthcare Systems: Integrating Research and Precision Medicine for Inflammatory Bowel Disease.}, journal = {Omics : a journal of integrative biology}, volume = {22}, number = {2}, pages = {119-126}, pmid = {28282257}, issn = {1557-8100}, mesh = {Animals ; Delivery of Health Care ; Genome, Human/genetics ; Genomics/methods ; Humans ; Inflammatory Bowel Diseases/genetics/*microbiology ; Microbiota/*physiology ; Precision Medicine/methods ; Research ; }, abstract = {Healthcare institutions face widespread challenges of delivering high-quality and cost-effective care, while keeping up with rapid advances in biomedical knowledge and technologies. Moreover, there is increased emphasis on developing personalized or precision medicine targeted to individuals or groups of patients who share a certain biomarker signature. Learning healthcare systems (LHS) have been proposed for integration of research and clinical practice to fill major knowledge gaps, improve care, reduce healthcare costs, and provide precision care. To date, much discussion in this context has focused on the potential of human genomic data, and not yet on human microbiome data. Rapid advances in human microbiome research suggest that profiling of, and interventions on, the human microbiome can provide substantial opportunity for improved diagnosis, therapeutics, risk management, and risk stratification. In this study, we discuss a potential role for microbiome science in LHSs. We first review the key elements of LHSs, and discuss possibilities of Big Data and patient engagement. We then consider potentials and challenges of integrating human microbiome research into clinical practice as part of an LHS. With rapid growth in human microbiome research, patient-specific microbial data will begin to contribute in important ways to precision medicine. Hence, we discuss how patient-specific microbial data can help guide therapeutic decisions and identify novel effective approaches for precision care of inflammatory bowel disease. To the best of our knowledge, this expert analysis makes an original contribution with new insights poised at the emerging intersection of LHSs, microbiome science, and postgenomics medicine.}, }
@article {pmid28279336, year = {2017}, author = {Gevers, D and Kugathasan, S and Knights, D and Kostic, AD and Knight, R and Xavier, RJ}, title = {A Microbiome Foundation for the Study of Crohn's Disease.}, journal = {Cell host &amp; microbe}, volume = {21}, number = {3}, pages = {301-304}, pmid = {28279336}, issn = {1934-6069}, support = {P30 DK036836/DK/NIDDK NIH HHS/United States ; P30 DK043351/DK/NIDDK NIH HHS/United States ; }, mesh = {Crohn Disease/*etiology/*microbiology/pathology ; *Gastrointestinal Microbiome ; Humans ; *Microbiota ; }, abstract = {Our 2014 study published in Cell Host &amp; Microbe, "The Treatment-Naive Microbiome in New-Onset Crohn's Disease," was designed to improve our understanding of the microbiome's role in Crohn's disease by studying a unique, well-suited cohort and sample set. This commentary provides a hindsight perspective of this original study as well as future outlook.}, }
@article {pmid28278350, year = {2018}, author = {Champer, M and Wong, AM and Champer, J and Brito, IL and Messer, PW and Hou, JY and Wright, JD}, title = {The role of the vaginal microbiome in gynaecological cancer.}, journal = {BJOG : an international journal of obstetrics and gynaecology}, volume = {125}, number = {3}, pages = {309-315}, doi = {10.1111/1471-0528.14631}, pmid = {28278350}, issn = {1471-0528}, mesh = {Female ; *Genital Neoplasms, Female/microbiology/pathology ; Humans ; Microbiota/*physiology ; *Probiotics ; *Vagina/microbiology/physiology/physiopathology ; Women's Health ; }, abstract = {UNLABELLED: Human microbiome research has shown commensal bacteria to be a major factor in both wellness and disease pathogenesis. Interest in the microbiome has recently expanded beyond the gut to include a multitude of other organ systems for which the microbiome may have health implications. Here, we review the role of the vaginal microbiome in health and disease, with a particular focus on gynaecologic malignancies. Further, we suggest that it may be possible to expand the use of probiotics in the treatment of gynaecological cancers.<br><br>TWEETABLE ABSTRACT: A review of the research to date on the relation between the vaginal microbiome and gynaecological cancers.}, }
@article {pmid30202360, year = {2017}, author = {Gardner, CD and Hauser, ME}, title = {Food Revolution.}, journal = {American journal of lifestyle medicine}, volume = {11}, number = {5}, pages = {387-396}, pmid = {30202360}, issn = {1559-8276}, support = {R01 DK091831/DK/NIDDK NIH HHS/United States ; T32 HL007034/HL/NHLBI NIH HHS/United States ; }, abstract = {Recent research has found important links between poor dietary choices, a toxic food environment, and high national and global burdens of chronic diseases. These findings serve as an impetus for a Food Revolution. The Gardner Nutrition Studies Research Group, along with a diverse range of collaborators, has been focusing on solution-oriented research to help find answers to the problems that plague the current food system. Research topics include (1) a recently completed weight loss diet study contrasting Healthy Low-Fat to Healthy Low-Carbohydrate diets among 609 overweight and obese adults; (2) a quasi-experimental study conducted among Stanford undergraduates that examined social and environmental, rather than health-focused, motivations for dietary change; (3) links between dietary fiber, the human microbiome, and immune function; and (4) ongoing collaborations with university chefs to create unapologetically delicious food for campus dining halls that is also healthy and environmentally sustainable. Most of these approaches emphasize plant-based diets. The decreased consumption of animal products has created some concern over the ability of one to obtain adequate protein intake. Evidence is presented that adequate protein is easily obtainable from vegetarian, vegan, and other diets that contain significantly less meat and fewer animal foods than the standard American diet.}, }
@article {pmid28266933, year = {2017}, author = {Franasiak, JM and Scott, RT}, title = {Endometrial microbiome.}, journal = {Current opinion in obstetrics &amp; gynecology}, volume = {29}, number = {3}, pages = {146-152}, doi = {10.1097/GCO.0000000000000357}, pmid = {28266933}, issn = {1473-656X}, mesh = {Endometrium/*microbiology ; Female ; Humans ; *Microbiota ; Pregnancy ; Pregnancy Outcome ; Reproductive Techniques, Assisted ; Vagina/microbiology ; }, abstract = {PURPOSE OF REVIEW: There have been great improvements in assisted reproduction in the recent decade; however, there are still a significant number of chromosomally normal blastocysts that fail to produce live births. The human microbiome is the totality of the microbes and their genomes that exist in and on the host. The understanding of its impact on health and human disease, particularly in human reproduction, is evolving.<br><br>RECENT FINDINGS: New technologies have empowered metagenomic sample analysis that allows for more fully characterizing the reproductive tract microbiome. With these technologies, we have determined not only that sites previously thought to be sterile in fact have robust microbiomes, but also have better characterized the normal and abnormal vaginal and endometrial microbiome.<br><br>SUMMARY: The understanding of the microbiome in health and human disease, in particular in relation to human reproduction, is in its infancy. As the reproductive tract dysbiosis are better characterized and understood, we may be better equipped to manipulate it more expertly.}, }
@article {pmid28257583, year = {2017}, author = {Le Bars, P and Matamoros, S and Montassier, E and Le Vacon, F and Potel, G and Soueidan, A and Jordana, F and de La Cochetière, MF}, title = {The oral cavity microbiota: between health, oral disease, and cancers of the aerodigestive tract.}, journal = {Canadian journal of microbiology}, volume = {63}, number = {6}, pages = {475-492}, doi = {10.1139/cjm-2016-0603}, pmid = {28257583}, issn = {1480-3275}, mesh = {Digestive System Neoplasms/*microbiology ; Gastrointestinal Microbiome ; Humans ; *Microbiota ; Mouth/*microbiology ; Mouth Diseases/microbiology ; }, abstract = {Many studies show that the human microbiome plays a critical role in the chronic pathologies of obesity, inflammatory bowel diseases, and diabetes. More recently, the interaction between cancer and the microbiome has been highlighted. Most studies have focused on the gut microbiota because it represents the most extensive bacterial community, and the body of evidence correlating it with gut syndromes is increasing. However, in the strict sense, the gastrointestinal (GI) tract begins in the oral cavity, and special attention should be paid to the specific flora of this cavity. This study reviewed the current knowledge about the various microbial ecosystems of the upper part of the GI tract and discussed their potential link to carcinogenesis. The overall composition of the microbial communities, as well as the presence or absence of "key species", in relation to carcinogenesis is addressed. Alterations in the oral microbiota can potentially be used to predict the risk of cancer. Molecular advances and the further monitoring of the microbiota will increase our understanding of the role of the microbiota in carcinogenesis and open new perspectives for future therapeutic and prophylactic modalities.}, }
@article {pmid28252578, year = {2017}, author = {Ames, NJ and Ranucci, A and Moriyama, B and Wallen, GR}, title = {The Human Microbiome and Understanding the 16S rRNA Gene in Translational Nursing Science.}, journal = {Nursing research}, volume = {66}, number = {2}, pages = {184-197}, pmid = {28252578}, issn = {1538-9847}, support = {Z99 CL999999//Intramural NIH HHS/United States ; }, mesh = {Bacterial Infections/*genetics/nursing ; Humans ; Infection Control/methods ; Microbiota/*genetics ; Nursing Methodology Research ; Polymerase Chain Reaction ; RNA, Ribosomal, 16S/*genetics ; }, abstract = {BACKGROUND: As more is understood regarding the human microbiome, it is increasingly important for nurse scientists and healthcare practitioners to analyze these microbial communities and their role in health and disease. 16S rRNA sequencing is a key methodology in identifying these bacterial populations that has recently transitioned from use primarily in research to having increased utility in clinical settings.<br><br>OBJECTIVES: The objectives of this review are to (a) describe 16S rRNA sequencing and its role in answering research questions important to nursing science; (b) provide an overview of the oral, lung, and gut microbiomes and relevant research; and (c) identify future implications for microbiome research and 16S sequencing in translational nursing science.<br><br>DISCUSSION: Sequencing using the 16S rRNA gene has revolutionized research and allowed scientists to easily and reliably characterize complex bacterial communities. This type of research has recently entered the clinical setting, one of the best examples involving the use of 16S sequencing to identify resistant pathogens, thereby improving the accuracy of bacterial identification in infection control. Clinical microbiota research and related requisite methods are of particular relevance to nurse scientists-individuals uniquely positioned to utilize these techniques in future studies in clinical settings.}, }
@article {pmid28244273, year = {2017}, author = {Hampton-Marcell, JT and Lopez, JV and Gilbert, JA}, title = {The human microbiome: an emerging tool in forensics.}, journal = {Microbial biotechnology}, volume = {10}, number = {2}, pages = {228-230}, pmid = {28244273}, issn = {1751-7915}, mesh = {Forensic Anthropology/*methods/trends ; Forensic Medicine/*methods/trends ; Humans ; *Microbiota ; }, }
@article {pmid28239609, year = {2016}, author = {Torbati, ME and Mitreva, M and Gopalakrishnan, V}, title = {Application of Taxonomic Modeling to Microbiota Data Mining for Detection of Helminth Infection in Global Populations.}, journal = {Data}, volume = {1}, number = {3}, pages = {}, pmid = {28239609}, issn = {2306-5729}, support = {R01 GM100387/GM/NIGMS NIH HHS/United States ; }, abstract = {Human microbiome data from genomic sequencing technologies is fast accumulating, giving us insights into bacterial taxa that contribute to health and disease. The predictive modeling of such microbiota count data for the classification of human infection from parasitic worms, such as helminths, can help in the detection and management across global populations. Real-world datasets of microbiome experiments are typically sparse, containing hundreds of measurements for bacterial species, of which only a few are detected in the bio-specimens that are analyzed. This feature of microbiome data produces the challenge of needing more observations for accurate predictive modeling and has been dealt with previously, using different methods of feature reduction. To our knowledge, integrative methods, such as transfer learning, have not yet been explored in the microbiome domain as a way to deal with data sparsity by incorporating knowledge of different but related datasets. One way of incorporating this knowledge is by using a meaningful mapping among features of these datasets. In this paper, we claim that this mapping would exist among members of each individual cluster, grouped based on phylogenetic dependency among taxa and their association to the phenotype. We validate our claim by showing that models incorporating associations in such a grouped feature space result in no performance deterioration for the given classification task. In this paper, we test our hypothesis by using classification models that detect helminth infection in microbiota of human fecal samples obtained from Indonesia and Liberia countries. In our experiments, we first learn binary classifiers for helminth infection detection by using Naive Bayes, Support Vector Machines, Multilayer Perceptrons, and Random Forest methods. In the next step, we add taxonomic modeling by using the SMART-scan module to group the data, and learn classifiers using the same four methods, to test the validity of the achieved groupings. We observed a 6% to 23% and 7% to 26% performance improvement based on the Area Under the receiver operating characteristic (ROC) Curve (AUC) and Balanced Accuracy (Bacc) measures, respectively, over 10 runs of 10-fold cross-validation. These results show that using phylogenetic dependency for grouping our microbiota data actually results in a noticeable improvement in classification performance for helminth infection detection. These promising results from this feasibility study demonstrate that methods such as SMART-scan can be utilized in the future for knowledge transfer from different but related microbiome datasets by phylogenetically-related functional mapping, to enable novel integrative biomarker discovery.}, }
@article {pmid28235227, year = {2017}, author = {Voigt, AY and Zeller, G and Bork, P}, title = {[Microbial Biomarkers for Early Cancer Detection].}, journal = {Deutsche medizinische Wochenschrift (1946)}, volume = {142}, number = {4}, pages = {267-274}, doi = {10.1055/s-0042-110193}, pmid = {28235227}, issn = {1439-4413}, mesh = {Bacteria/*isolation &amp; purification ; Bacterial Load/*methods ; Biomarkers/analysis ; Colon/*microbiology ; Colorectal Neoplasms/*diagnosis/*microbiology ; Early Detection of Cancer/*methods ; Evidence-Based Medicine ; Humans ; }, abstract = {The human microbiome - the vast amount of microbes that colonize our body - play an important role in maintaining our health. Changes in microbiome composition have been linked to multiple diseases including cancer. Although mechanisms and causalities of these associations still have to be uncovered, microbiome alterations across various stages of disease can be utilized for novel diagnostic and prognostic tests. Research on biomarkers extracted from the gut microbiome has in particular focused on colorectal cancer, where clinical use is already on the horizon. For example, multiple microbial taxonomic markers such as Fusobacterium nucleatum and other oral pathogens have been identified in human feces with potential for non-invasive diagnostics and prognostics. The article summarizes the recent developments, but also limitations and challenges for the development of microbiome-based biomarkers for cancer early detection.}, }
@article {pmid28217698, year = {2017}, author = {Bao, Y and Al, KF and Chanyi, RM and Whiteside, S and Dewar, M and Razvi, H and Reid, G and Burton, JP}, title = {Questions and challenges associated with studying the microbiome of the urinary tract.}, journal = {Annals of translational medicine}, volume = {5}, number = {2}, pages = {33}, pmid = {28217698}, issn = {2305-5839}, abstract = {Urologists are typically faced with clinical situations for which the microbiome may have been a contributing factor. Clinicians have a good understanding regarding the role of bacteria related to issues such as antibiotic resistance; however, they generally have a limited grasp of how the microbiome may relate to urological issues. The largest part of the human microbiome is situated in the gastrointestinal tract, and though this is mostly separated from the urinary system, bacterial dissemination and metabolic output by this community is thought to have a significant influence on urological conditions. Sites within the urogenital system that were once considered "sterile" may regularly have bacterial populations present. The health implications potentially extend all the way to the kidneys. This could affect urinary tract infections, bladder cancer, urinary incontinence and related conditions including the formation of kidney stones. Given the sensitivity of the methodologies employed, and the large potential for contamination when working with low abundance microbiomes, meticulous care in the analyses of urological samples at various sites is required. This review highlights the opportunities for urinary microbiome investigations and our experience in working with these low abundance samples in the urinary tract.}, }
@article {pmid28217695, year = {2017}, author = {Arora, HC and Eng, C and Shoskes, DA}, title = {Gut microbiome and chronic prostatitis/chronic pelvic pain syndrome.}, journal = {Annals of translational medicine}, volume = {5}, number = {2}, pages = {30}, pmid = {28217695}, issn = {2305-5839}, abstract = {Analysis of the human microbiome continues to reveal new and previously unrealized associations between microbial dysbiosis and disease. Novel approaches to bacterial identification using culture-independent methods allow practitioners to discern the presence of alterations in the taxa and diversity of the microbiome and identify correlations with disease processes. While some of these diseases that have been extensively studied are well-defined in their etiology and treatment methods (colorectal cancer), others have provided much more significant challenges in both diagnosis and treatment. One such condition, chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS), has several etiological and potentiating contributions from infection, inflammation, central nervous system (CNS) changes, stress, and central sensitization-all factors that play important roles in the crosstalk between the human body and its microbiome. No singular cause of CP/CPPS has been identified and it is most likely a syndrome with multifactorial causes. This heterogeneity and ambiguity are sources of significant frustration for patients and providers alike. Despite multiple attempts, treatment of chronic prostatitis with monotherapy has seen limited success, which is thought to be due to its heterogeneous nature. Phenotypic approaches to both classify the disease and direct treatment for CP/CPPS have proven beneficial in these patients, but questions still remain regarding etiology. Newer microbiome research has found correlations between symptom scores and disease severity and the degree of dysbiosis in urine and gut (stool) microbiomes in these patients as compared to un-afflicted controls. These findings present potential new diagnostic and therapeutic targets in CP/CPPS patients.}, }
@article {pmid28217692, year = {2017}, author = {Shoskes, DA and Macoska, JA}, title = {Preface to the human microbiome in urologic health and disease.}, journal = {Annals of translational medicine}, volume = {5}, number = {2}, pages = {27}, doi = {10.21037/atm.2017.01.12}, pmid = {28217692}, issn = {2305-5839}, }
@article {pmid28216014, year = {2017}, author = {Bhattacharyya, M and Ghosh, T and Shankar, S and Tomar, N}, title = {The conserved phylogeny of blood microbiome.}, journal = {Molecular phylogenetics and evolution}, volume = {109}, number = {}, pages = {404-408}, doi = {10.1016/j.ympev.2017.02.001}, pmid = {28216014}, issn = {1095-9513}, mesh = {Archaea/classification ; Bacteria/*classification ; Bacterial Proteins/genetics ; *Biological Evolution ; Blood/*microbiology ; Fungal Proteins/genetics ; Humans ; *Microbiota ; Phylogeny ; }, abstract = {The proliferation and intensification of diseases have forced every researcher to take actions for a robust understanding of the organisms. This demands deep knowledge about the cells and tissues in an organ and its entire surroundings, more precisely the microbiome community which involves viruses, bacteria, archaea, among others. They play an important role in the function of our body, and act both as a deterrent as well as shelter for diseases. Therefore, it is pertinent to study the relation within the microbiome in a human body. In this work, we analyze the sequence data provided through the Human Microbiome Project to explore evolutionary relations within blood microbiome. The objective is to analyze the common proteins present in the different microbes in the blood and find their phylogeny. The analysis of the phylogenetic relation between these species provides important insights about the conservedness of phylogeny of blood microbiome. Interestingly, the co-existence of five of those common proteins is observed in human too.}, }
@article {pmid28203137, year = {2017}, author = {Farooq, S and Farooq, R and Nahvi, N}, title = {Comamonas testosteroni: Is It Still a Rare Human Pathogen?.}, journal = {Case reports in gastroenterology}, volume = {11}, number = {1}, pages = {42-47}, pmid = {28203137}, issn = {1662-0631}, abstract = {Comamonas testosteroni (formally Pseudomonas testosteroni) is common environmental bacterium that is not part of the human microbiome. Since its identification as a human pathogen in 1987, numerous reports have drizzled in, implicating this organism for various infections. Although these organisms are of low virulence, some of their obscurity perhaps is due to the incapability of clinical laboratories to identify them. Most of the reported cases are bloodstream infections. We report a case of gastroenteritis caused by this organism in a 65-year-old female with colostomy in situ.}, }
@article {pmid28194314, year = {2017}, author = {Hannigan, GD and Zheng, Q and Meisel, JS and Minot, SS and Bushman, FD and Grice, EA}, title = {Evolutionary and functional implications of hypervariable loci within the skin virome.}, journal = {PeerJ}, volume = {5}, number = {}, pages = {e2959}, pmid = {28194314}, issn = {2167-8359}, support = {P30 AR069589/AR/NIAMS NIH HHS/United States ; R00 AR060873/AR/NIAMS NIH HHS/United States ; R01 AR066663/AR/NIAMS NIH HHS/United States ; T32 HG000046/HG/NHGRI NIH HHS/United States ; }, abstract = {Localized genomic variability is crucial for the ongoing conflicts between infectious microbes and their hosts. An understanding of evolutionary and adaptive patterns associated with genomic variability will help guide development of vaccines and antimicrobial agents. While most analyses of the human microbiome have focused on taxonomic classification and gene annotation, we investigated genomic variation of skin-associated viral communities. We evaluated patterns of viral genomic variation across 16 healthy human volunteers. Human papillomavirus (HPV) and Staphylococcus phages contained 106 and 465 regions of diversification, or hypervariable loci, respectively. Propionibacterium phage genomes were minimally divergent and contained no hypervariable loci. Genes containing hypervariable loci were involved in functions including host tropism and immune evasion. HPV and Staphylococcus phage hypervariable loci were associated with purifying selection. Amino acid substitution patterns were virus dependent, as were predictions of their phenotypic effects. We identified diversity generating retroelements as one likely mechanism driving hypervariability. We validated these findings in an independently collected skin metagenomic sequence dataset, suggesting that these features of skin virome genomic variability are widespread. Our results highlight the genomic variation landscape of the skin virome and provide a foundation for better understanding community viral evolution and the functional implications of genomic diversification of skin viruses.}, }
@article {pmid28184287, year = {2017}, author = {Janowski, A and Newland, J}, title = {Of the Phrensy: an update on the epidemiology and pathogenesis of bacterial meningitis in the pediatric population.}, journal = {F1000Research}, volume = {6}, number = {}, pages = {}, pmid = {28184287}, issn = {2046-1402}, abstract = {In the past century, advances in antibiotics and vaccination have dramatically altered the incidence and clinical outcomes of bacterial meningitis. We review the shifting epidemiology of meningitis in children, including after the implementation of vaccines that target common meningitic pathogens and the introduction of intrapartum antibiotic prophylaxis offered to mothers colonized with Streptococcus agalactiae. We also discuss what is currently known about the pathogenesis of meningitis. Recent studies of the human microbiome have illustrated dynamic relationships of bacterial and viral populations with the host, which may potentiate the risk of bacterial meningitis.}, }
@article {pmid28183913, year = {2017}, author = {Levin, BJ and Huang, YY and Peck, SC and Wei, Y and Martínez-Del Campo, A and Marks, JA and Franzosa, EA and Huttenhower, C and Balskus, EP}, title = {A prominent glycyl radical enzyme in human gut microbiomes metabolizes trans-4-hydroxy-l-proline.}, journal = {Science (New York, N.Y.)}, volume = {355}, number = {6325}, pages = {}, pmid = {28183913}, issn = {1095-9203}, support = {P30 DK043351/DK/NIDDK NIH HHS/United States ; U54 DE023798/DE/NIDCR NIH HHS/United States ; }, mesh = {Amino Acid Motifs ; Anaerobiosis ; Gastrointestinal Microbiome/*genetics ; Gastrointestinal Tract/*microbiology ; Humans ; Hydroxyproline/*metabolism ; Metagenome ; Proline Oxidase/*chemistry/*genetics/metabolism ; Propanediol Dehydratase/chemistry/genetics ; Protein Processing, Post-Translational ; Sequence Alignment ; }, abstract = {The human microbiome encodes vast numbers of uncharacterized enzymes, limiting our functional understanding of this community and its effects on host health and disease. By incorporating information about enzymatic chemistry into quantitative metagenomics, we determined the abundance and distribution of individual members of the glycyl radical enzyme superfamily among the microbiomes of healthy humans. We identified many uncharacterized family members, including a universally distributed enzyme that enables commensal gut microbes and human pathogens to dehydrate trans-4-hydroxy-l-proline, the product of the most abundant human posttranslational modification. This "chemically guided functional profiling" workflow can therefore use ecological context to facilitate the discovery of enzymes in microbial communities.}, }
@article {pmid28179983, year = {2017}, author = {Bilen, M and Mbogning, MD and Cadoret, F and Dubourg, G and Daoud, Z and Fournier, PE and Raoult, D}, title = {'Pygmaiobacter massiliensis' sp. nov., a new bacterium isolated from the human gut of a Pygmy woman.}, journal = {New microbes and new infections}, volume = {16}, number = {}, pages = {37-38}, pmid = {28179983}, issn = {2052-2975}, abstract = {This study supports the main characteristics of a new genus 'Pygmaiobacter' and a new species 'Pygmaiobacter massiliensis' strain Marseille-P3336 (CSUR P3336); that was isolated from a stool sample of a healthy 47-year-old Pygmy woman. The Institut Fédératif de Recherche ethics committee, gave approval for this study under the number 09-022. Samples were collected for microbial content description as part of the human microbiome description by culturomics.}, }
@article {pmid28179566, year = {2017}, author = {Zhang, SL and Bai, L and Goel, N and Bailey, A and Jang, CJ and Bushman, FD and Meerlo, P and Dinges, DF and Sehgal, A}, title = {Human and rat gut microbiome composition is maintained following sleep restriction.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {114}, number = {8}, pages = {E1564-E1571}, pmid = {28179566}, issn = {1091-6490}, support = {P30 AI045008/AI/NIAID NIH HHS/United States ; R01 NR004281/NR/NINR NIH HHS/United States ; R25 MH060490/MH/NIMH NIH HHS/United States ; T32 HL007713/HL/NHLBI NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Adult ; Animals ; Cognition/*physiology ; DNA, Bacterial/isolation &amp; purification ; Dysbiosis/microbiology/*physiopathology ; Feces/microbiology ; Female ; Gastrointestinal Microbiome/*physiology ; Gastrointestinal Tract/*microbiology/physiopathology ; Genes, rRNA ; Healthy Volunteers ; Humans ; Male ; Metabolic Diseases/microbiology/*physiopathology ; Middle Aged ; RNA, Ribosomal, 16S/genetics ; Rats ; Rats, Sprague-Dawley ; Sleep Deprivation/microbiology/*physiopathology ; }, abstract = {Insufficient sleep increasingly characterizes modern society, contributing to a host of serious medical problems. Loss of sleep is associated with metabolic diseases such as obesity and diabetes, cardiovascular disorders, and neurological and cognitive impairments. Shifts in gut microbiome composition have also been associated with the same pathologies; therefore, we hypothesized that sleep restriction may perturb the gut microbiome to contribute to a disease state. In this study, we examined the fecal microbiome by using a cross-species approach in both rat and human studies of sleep restriction. We used DNA from hypervariable regions (V1-V2) of 16S bacteria rRNA to define operational taxonomic units (OTUs) of the microbiome. Although the OTU richness of the microbiome is decreased by sleep restriction in rats, major microbial populations are not altered. Only a single OTU, TM7-3a, was found to increase with sleep restriction of rats. In the human microbiome, we find no overt changes in the richness or composition induced by sleep restriction. Together, these results suggest that the microbiome is largely resistant to changes during sleep restriction.}, }
@article {pmid28179006, year = {2017}, author = {Manor, O and Borenstein, E}, title = {Revised computational metagenomic processing uncovers hidden and biologically meaningful functional variation in the human microbiome.}, journal = {Microbiome}, volume = {5}, number = {1}, pages = {19}, pmid = {28179006}, issn = {2049-2618}, support = {DP2 AT007802/AT/NCCIH NIH HHS/United States ; P30 DK089507/DK/NIDDK NIH HHS/United States ; R01 DK095869/DK/NIDDK NIH HHS/United States ; }, mesh = {Bacteria/*genetics ; Computational Biology/*methods ; DNA, Bacterial/genetics ; Gastrointestinal Microbiome/*genetics ; Gastrointestinal Tract/*microbiology ; Genetic Variation/genetics ; Humans ; Metagenomics/*methods ; }, abstract = {BACKGROUND: Recent metagenomic analyses of the human gut microbiome identified striking variability in its taxonomic composition across individuals. Notably, however, these studies often reported marked functional uniformity, with relatively little variation in the microbiome's gene composition or in its overall metabolic capacity.<br><br>RESULTS: Here, we address this surprising discrepancy between taxonomic and functional variations and set out to track its origins. Specifically, we demonstrate that the functional uniformity observed in microbiome studies can be attributed, at least partly, to common computational metagenomic processing procedures that mask true functional variation across microbiome samples. We identify several such procedures, including commonly used practices for gene abundance normalization, mapping of gene families to functional pathways, and gene family aggregation. We show that accounting for these factors and using revised metagenomic processing procedures uncovers such hidden functional variation, significantly increasing observed variation in the abundance of functional elements across samples. Importantly, we find that this uncovered variation is biologically meaningful and that it is associated with both host identity and health.<br><br>CONCLUSIONS: Accurate characterization of functional variation in the microbiome is essential for comparative metagenomic analyses in health and disease. Our finding that metagenomic processing procedures mask underlying and biologically meaningful functional variation therefore highlights an important challenge such studies may face. Alternative schemes for metagenomic processing that uncover this hidden functional variation can facilitate improved metagenomic analysis and help pinpoint disease- and host-associated shifts in the microbiome's functional capacity.}, }
@article {pmid28178947, year = {2017}, author = {Wadsworth, WD and Argiento, R and Guindani, M and Galloway-Pena, J and Shelburne, SA and Vannucci, M}, title = {An integrative Bayesian Dirichlet-multinomial regression model for the analysis of taxonomic abundances in microbiome data.}, journal = {BMC bioinformatics}, volume = {18}, number = {1}, pages = {94}, pmid = {28178947}, issn = {1471-2105}, support = {L30 CA209245/CA/NCI NIH HHS/United States ; P30 CA016672/CA/NCI NIH HHS/United States ; T32 CA096520/CA/NCI NIH HHS/United States ; }, mesh = {Algorithms ; Bacteria/*classification ; Bayes Theorem ; Computer Simulation ; Humans ; *Linear Models ; Markov Chains ; *Microbiota ; Monte Carlo Method ; }, abstract = {BACKGROUND: The Human Microbiome has been variously associated with the immune-regulatory mechanisms involved in the prevention or development of many non-infectious human diseases such as autoimmunity, allergy and cancer. Integrative approaches which aim at associating the composition of the human microbiome with other available information, such as clinical covariates and environmental predictors, are paramount to develop a more complete understanding of the role of microbiome in disease development.<br><br>RESULTS: In this manuscript, we propose a Bayesian Dirichlet-Multinomial regression model which uses spike-and-slab priors for the selection of significant associations between a set of available covariates and taxa from a microbiome abundance table. The approach allows straightforward incorporation of the covariates through a log-linear regression parametrization of the parameters of the Dirichlet-Multinomial likelihood. Inference is conducted through a Markov Chain Monte Carlo algorithm, and selection of the significant covariates is based upon the assessment of posterior probabilities of inclusions and the thresholding of the Bayesian false discovery rate. We design a simulation study to evaluate the performance of the proposed method, and then apply our model on a publicly available dataset obtained from the Human Microbiome Project which associates taxa abundances with KEGG orthology pathways. The method is implemented in specifically developed R code, which has been made publicly available.<br><br>CONCLUSIONS: Our method compares favorably in simulations to several recently proposed approaches for similarly structured data, in terms of increased accuracy and reduced false positive as well as false negative rates. In the application to the data from the Human Microbiome Project, a close evaluation of the biological significance of our findings confirms existing associations in the literature.}, }
@article {pmid28178564, year = {2017}, author = {Redinbo, MR}, title = {Microbial Molecules from the Multitudes within Us.}, journal = {Cell metabolism}, volume = {25}, number = {2}, pages = {230-232}, doi = {10.1016/j.cmet.2017.01.013}, pmid = {28178564}, issn = {1932-7420}, support = {P30 ES010126/ES/NIEHS NIH HHS/United States ; R01 CA098468/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; *Gastrointestinal Microbiome ; Humans ; *Symbiosis ; }, abstract = {Chemists demonstrate in Cell that intestinal microbes are capable of synthesizing metabolites that look like clinical drugs and inhibit human targets. These results provide molecular resolution to the field of mammalian-microbial mutualism and highlight the potential for natural product discovery from the multitudes within us.}, }
@article {pmid28165863, year = {2017}, author = {Holscher, HD}, title = {Dietary fiber and prebiotics and the gastrointestinal microbiota.}, journal = {Gut microbes}, volume = {8}, number = {2}, pages = {172-184}, pmid = {28165863}, issn = {1949-0984}, mesh = {Animals ; Bacteria/classification/genetics/isolation &amp; purification/metabolism ; Dietary Fiber/analysis/*metabolism ; *Gastrointestinal Microbiome ; Gastrointestinal Tract/metabolism/*microbiology ; Humans ; Prebiotics/*analysis ; }, abstract = {The gastrointestinal microbiota has an important role in human health, and there is increasing interest in utilizing dietary approaches to modulate the composition and metabolic function of the microbial communities that colonize the gastrointestinal tract to improve health, and prevent or treat disease. One dietary strategy for modulating the microbiota is consumption of dietary fiber and prebiotics that can be metabolized by microbes in the gastrointestinal tract. Human alimentary enzymes are not able to digest most complex carbohydrates and plant polysaccharides. Instead, these polysaccharides are metabolized by microbes which generate short-chain fatty acids (SCFAs), including acetate, propionate, and butyrate. This article reviews the current knowledge of the impact of fiber and prebiotic consumption on the composition and metabolic function of the human gastrointestinal microbiota, including the effects of physiochemical properties of complex carbohydrates, adequate intake and treatment dosages, and the phenotypic responses related to the composition of the human microbiota.}, }
@article {pmid28164851, year = {2017}, author = {Li, JV and Swann, J and Marchesi, JR}, title = {Biology of the Microbiome 2: Metabolic Role.}, journal = {Gastroenterology clinics of North America}, volume = {46}, number = {1}, pages = {37-47}, doi = {10.1016/j.gtc.2016.09.006}, pmid = {28164851}, issn = {1558-1942}, mesh = {Animals ; Bacteria/*metabolism ; Blood Chemical Analysis ; Feces/chemistry ; Gastrointestinal Microbiome/*physiology ; Humans ; Magnetic Resonance Spectroscopy ; Mass Spectrometry ; *Metabolome ; Urinalysis ; }, abstract = {The human microbiome is a new frontier in biology and one that is helping to define what it is to be human. Recently, we have begun to understand that the "communication" between the host and its microbiome is via a metabolic superhighway. By interrogating and understanding the molecules involved we may start to know who the main players are, and how we can modulate them and the mechanisms of health and disease.}, }
@article {pmid28155809, year = {2017}, author = {Rivera-Pérez, JI and González, AA and Toranzos, GA}, title = {From Evolutionary Advantage to Disease Agents: Forensic Reevaluation of Host-Microbe Interactions and Pathogenicity.}, journal = {Microbiology spectrum}, volume = {5}, number = {1}, pages = {}, pmid = {28155809}, issn = {2165-0497}, support = {R25 GM061151/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; *Biological Evolution ; Helicobacter pylori/*pathogenicity ; *Host-Pathogen Interactions ; Humans ; JC Virus/*pathogenicity ; Legionella/*pathogenicity ; }, abstract = {As the "human microbiome era" continues, there is an increasing awareness of our resident microbiota and its indispensable role in our fitness as holobionts. However, the host-microbe relationship is not so clearly defined for some human symbionts. Here we discuss examples of "accidental pathogens," meaning previously nonpathogenic and/or environmental microbes thought to have inadvertently experienced an evolutionary shift toward pathogenicity. For instance, symbionts such as Helicobacter pylori and JC polyomavirus have been shown to have accompanied humans since prehistoric times and are still abundant in extant populations as part of the microbiome. And yet, the relationship between a subgroup of these microbes and their human hosts seems to have changed with time, and they have recently gained notoriety as gastrointestinal and neuropathogens, respectively. On the other hand, environmental microbes such as Legionella spp. have recently experienced a shift in host range and are now a major problem in industrialized countries as a result of artificial ecosystems. Other variables involved in this accidental phenomenon could be the apparent change or reduction in the diversity of human-associated microbiota because of modern medicine and lifestyles. All of this could result in an increased prevalence of accidental pathogens in the form of emerging pathogens.}, }
@article {pmid28151608, year = {2016}, author = {Błaszkowska, J and Góralska, K}, title = {Clinical cases of parasitoses and fungal infections important from medical point of view.}, journal = {Annals of parasitology}, volume = {62}, number = {4}, pages = {255-265}, doi = {10.17420/ap6204.61}, pmid = {28151608}, issn = {2299-0631}, mesh = {Animals ; Humans ; Mycoses/microbiology/*pathology ; Parasitic Diseases/parasitology/*pathology ; Zoonoses ; }, abstract = {Most important infectious diseases which pose a risk to human health and life are associated with parasites transmitted by a variety of arthropod vectors, or from animal to man. Some of these (malaria, toxoplasmosis, leishmaniosis, dirofilariosis, alveococcosis, cystic echinococcosis) still represent a serious public health problem in many regions in the world. This review describes the epidemiological and clinical aspects of important parasitoses and fungal infections from a medical point of view. It should be emphasized that the development of invasive disease depends on both host (susceptibility/resistance) and parasite factors (pathogenicity/virulence); an immunocompromised state can favour opportunistic parasitic infections: toxoplasmosis, cryptosporidiosis, giardiosis, cyclosporidiosis, blastocystosis and strongyloidosis. This article highlights the role of free-living amoebae in the pathogenesis and transmission of human diseases, the high pathogenicity of Echinococcus multilocularis, and the growing importance of ticks as a reservoir and vector for numerous dangerous pathogens (e.g., Borrelia burgdorferi, Anaplasma phagocytophilum, Babesia microti). It also discusses the diagnostic problems of toxoplasmosis including cross-reactions in serological tests and reviews the search for new drugs and vaccines against toxoplasmosis. Attention is increasingly paid to the role played by the human microbiome in maintaining homeostasis and in the development of fungal infections. This review also presents the most common human superficial fungal infections and the role of Candida albicans infection in the pathogenesis of irritable bowel syndrome.}, }
@article {pmid28146577, year = {2017}, author = {Traykova, D and Schneider, B and Chojkier, M and Buck, M}, title = {Blood Microbiome Quantity and the Hyperdynamic Circulation in Decompensated Cirrhotic Patients.}, journal = {PloS one}, volume = {12}, number = {2}, pages = {e0169310}, pmid = {28146577}, issn = {1932-6203}, support = {R01 DK084139/DK/NIDDK NIH HHS/United States ; R41 HL122022/HL/NHLBI NIH HHS/United States ; R41 HL127919/HL/NHLBI NIH HHS/United States ; RC1 DK087031/DK/NIDDK NIH HHS/United States ; }, mesh = {Aged ; Bacteria/classification/genetics ; Biomarkers ; Case-Control Studies ; Cytokines/genetics/metabolism ; Gastrointestinal Microbiome ; Gene Expression Regulation ; *Hemodynamics ; Humans ; Liver Cirrhosis/*complications/diagnosis/etiology/*physiopathology ; Liver Function Tests ; Macrophages/immunology/metabolism ; Male ; Metagenome ; Metagenomics/methods ; *Microbiota ; Middle Aged ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism ; Nitric Oxide/metabolism ; Sepsis/*etiology ; }, abstract = {BACKGROUND: Recently, a complex microbiome was comprehensibly characterized in the serum and ascitic fluid of cirrhotic patients. In the current study, we investigated for the first time the induction of inflammatory pathways and Nitric Oxide, as well as the systemic hemodynamics in conjunction with the blood microbiome in a Child-Pugh class B cirrhotic cohort.<br><br>METHODS AND FINDINGS: We used the Intestinal Infections Microbial DNA qPCR Array to screen for 53 bacterial DNA from the gut in the blood. Assays were designed using the 16S rRNA gene as a target, and PCR amplification primers (based on the Human Microbiome Project) and hydrolysis-probe detection. Eighteen systemic hemodynamic parameters were measured non-invasively by impedance cardiography using the BioZ ICG monitor. The inflammatory response was assessed by measuring blood cytokines, Nitric Oxide RNA arrays, and Nitric Oxide. In the blood of this cirrhotic cohort, we detected 19 of 53 bacterial species tested. The number of bacterial species was markedly increased in the blood of cirrhotic patients compared to control individuals (0.2+/-0.4 vs 3.1+/-2.3; 95% CI: 1.3 to 4.9; P = 0.0030). The total bacterial DNA was also increased in the blood of cirrhotic subjects compared to control subjects (0.2+/- 1.1 vs 41.8+/-132.1; 95% CI: 6.0 to 77.2; P = 0.0022). In the cirrhotic cohort, the Cardiac Output increased by 37% and the Systemic Vascular Resistance decreased by 40% (P< 0.00001 for both compared to control subjects). Systemic Vascular Resistance was inversely correlated to blood bacterial DNA quantity (- 0.621; 95% CI -0.843 to -0.218; P = 0.0060), blood bacterial species number (- 0.593; 95% CI -0.83 to -0.175; P = 0.0095; logistic regression: Chi Square = 5.8877; P = 0.0152), and serum Nitric Oxide (- 0.705; 95% CI -0.881 to -0.355; P = 0.0011). Many members of the Nitric Oxide signaling pathway gene family were increased in cirrhotic subjects.<br><br>CONCLUSIONS: Our study identified blood bacterial DNA in ~ 90% of the cirrhotic patients without clinical evidences of infection, and suggests that the quantity of bacterial DNA in blood may stimulate signaling pathways, including Nitric Oxide, that could decrease systemic vascular resistance and increase cardiac output.}, }
@article {pmid28134778, year = {2017}, author = {Dey, M}, title = {Toward a Personalized Approach in Prebiotics Research.}, journal = {Nutrients}, volume = {9}, number = {2}, pages = {}, pmid = {28134778}, issn = {2072-6643}, mesh = {Diet ; Dietary Fiber/administration &amp; dosage ; Fermentation ; Gastrointestinal Microbiome ; Gastrointestinal Tract/microbiology ; Humans ; Nutritional Sciences/*trends ; Prebiotics/*administration &amp; dosage ; Precision Medicine ; }, abstract = {Recent characterization of the human microbiome and its influences on health have led to dramatic conceptual shifts in dietary bioactives research. Prebiotic foods that include many dietary fibers and resistant starches are perceived as beneficial for maintaining a healthy gut microbiota. This article brings forward some current perspectives in prebiotic research to discuss why reporting of individual variations in response to interventions will be important to discern suitability of prebiotics as a disease prevention tool.}, }
@article {pmid28120409, year = {2017}, author = {Pechal, JL and Schmidt, CJ and Jordan, HR and Benbow, ME}, title = {Frozen: Thawing and Its Effect on the Postmortem Microbiome in Two Pediatric Cases.}, journal = {Journal of forensic sciences}, volume = {62}, number = {5}, pages = {1399-1405}, doi = {10.1111/1556-4029.13419}, pmid = {28120409}, issn = {1556-4029}, mesh = {Adolescent ; Child ; Female ; *Freezing ; High-Throughput Nucleotide Sequencing ; Humans ; Male ; *Microbiota ; *Postmortem Changes ; RNA, Ribosomal, 16S/genetics ; *Transition Temperature ; }, abstract = {Previous postmortem microbiome studies have focused on characterizing taxa turnover during an undisturbed decomposition process. How coexisting conditions (e.g., frozen, buried, burned) affect the human microbiome at the time of discovery is less well understood. Microbiome data were collected from two pediatric cases at the Wayne County Medical Examiner in Michigan. The bodies were found frozen, hidden in a freezer for an extended time. Microbial communities were sampled from six external anatomic locations at three time points during the thawing process, prior to autopsy. The 16S rRNA V4 gene amplicon region was sequenced using high-throughput sequencing (Illumina MiSeq). Microbial diversity increased, and there was a distinct shift in microbial community structure and abundance throughout the thawing process. Overall, these data demonstrate that the postmortem human microbiome changes during the thawing process, and have important forensic implications when bodies have been substantially altered, modified, and concealed after death.}, }
@article {pmid28111783, year = {2017}, author = {Xu, L and Paterson, AD and Xu, W}, title = {Bayesian latent variable models for hierarchical clustered count outcomes with repeated measures in microbiome studies.}, journal = {Genetic epidemiology}, volume = {41}, number = {3}, pages = {221-232}, doi = {10.1002/gepi.22031}, pmid = {28111783}, issn = {1098-2272}, mesh = {Adolescent ; Adult ; Age Factors ; Aged ; *Algorithms ; *Bayes Theorem ; *Cluster Analysis ; DNA, Bacterial/*genetics ; Feces/microbiology ; Female ; Humans ; Markov Chains ; Microbiota/*genetics ; Middle Aged ; *Models, Genetic ; Models, Statistical ; Monte Carlo Method ; Obesity/genetics ; Research Design ; Thinness/genetics ; Twin Studies as Topic ; Young Adult ; }, abstract = {Motivated by the multivariate nature of microbiome data with hierarchical taxonomic clusters, counts that are often skewed and zero inflated, and repeated measures, we propose a Bayesian latent variable methodology to jointly model multiple operational taxonomic units within a single taxonomic cluster. This novel method can incorporate both negative binomial and zero-inflated negative binomial responses, and can account for serial and familial correlations. We develop a Markov chain Monte Carlo algorithm that is built on a data augmentation scheme using Pólya-Gamma random variables. Hierarchical centering and parameter expansion techniques are also used to improve the convergence of the Markov chain. We evaluate the performance of our proposed method through extensive simulations. We also apply our method to a human microbiome study.}, }
@article {pmid28111598, year = {2016}, author = {Kao, MS and Wang, Y and Marito, S and Huang, S and Lin, WZ and Gangoiti, JA and Barshop, BA and Hyun, C and Lee, WR and Sanford, JA and Gallo, RL and Ran, Y and Chen, WT and Huang, CJ and Hsieh, MF and Huang, CM}, title = {The mPEG-PCL Copolymer for Selective Fermentation of Staphylococcus lugdunensis Against Candida parapsilosis in the Human Microbiome.}, journal = {Journal of microbial &amp; biochemical technology}, volume = {8}, number = {4}, pages = {259-265}, pmid = {28111598}, issn = {1948-5948}, support = {R41 AR065260/AR/NIAMS NIH HHS/United States ; }, abstract = {Many human skin diseases, such as seborrheic dermatitis, potentially occur due to the over-growth of fungi. It remains a challenge to develop fungicides with a lower risk of generating resistant fungi and non-specifically killing commensal microbes. Our probiotic approaches using a selective fermentation initiator of skin commensal bacteria, fermentation metabolites or their derivatives provide novel therapeutics to rein in the over-growth of fungi. Staphylococcus lugdunensis (S. lugdunensis) bacteria and Candida parapsilosis (C. parapsilosis) fungi coexist in the scalp microbiome. S. lugdunensis interfered with the growth of C. parapsilosis via fermentation. A methoxy poly(ethylene glycol)-b-poly(ε-caprolactone) (mPEG-PCL) copolymer functioned as a selective fermentation initiator of S. lugdunensis, selectively triggering the S. lugdunensis fermentation to produce acetic and isovaleric acids. The acetic acid and its pro-drug diethyleneglycol diacetate (Ac-DEG-Ac) effectively suppressed the growth of C. parapsilosis in vitro and impeded the fungal expansion in the human dandruff. We demonstrate for the first time that S. lugdunensis is a skin probiotic bacterium that can exploit mPEG-PCL to yield fungicidal short-chain fatty acids (SCFAs). The concept of bacterial fermentation as a part of skin immunity to re-balance the dysbiotic microbiome warrants a novel avenue for studying the probiotic function of the skin microbiome in promoting health.}, }
@article {pmid28111203, year = {2017}, author = {Manor, O and Borenstein, E}, title = {Systematic Characterization and Analysis of the Taxonomic Drivers of Functional Shifts in the Human Microbiome.}, journal = {Cell host &amp; microbe}, volume = {21}, number = {2}, pages = {254-267}, pmid = {28111203}, issn = {1934-6069}, support = {DP2 AT007802/AT/NCCIH NIH HHS/United States ; }, mesh = {Actinobacteria/classification ; Bacteroides/classification ; Communicable Diseases/microbiology ; *Computational Biology ; Databases, Genetic ; Diabetes Mellitus, Type 2/microbiology ; Firmicutes/classification ; Genome, Microbial ; Humans ; Metagenomics ; *Microbiota ; Phylogeny ; Proteobacteria/classification ; *Software ; }, abstract = {Comparative analyses of the human microbiome have identified both taxonomic and functional shifts that are associated with numerous diseases. To date, however, microbiome taxonomy and function have mostly been studied independently and the taxonomic drivers of functional imbalances have not been systematically identified. Here, we present FishTaco, an analytical and computational framework that integrates taxonomic and functional comparative analyses to accurately quantify taxon-level contributions to disease-associated functional shifts. Applying FishTaco to several large-scale metagenomic cohorts, we show that shifts in the microbiome's functional capacity can be traced back to specific taxa. Furthermore, the set of taxa driving functional shifts and their contribution levels vary markedly between functions. We additionally find that similar functional imbalances in different diseases are driven by both disease-specific and shared taxa. Such integrated analysis of microbiome ecological and functional dynamics can inform future microbiome-based therapy, pinpointing putative intervention targets for manipulating the microbiome's functional capacity.}, }
@article {pmid28111075, year = {2017}, author = {Guo, CJ and Chang, FY and Wyche, TP and Backus, KM and Acker, TM and Funabashi, M and Taketani, M and Donia, MS and Nayfach, S and Pollard, KS and Craik, CS and Cravatt, BF and Clardy, J and Voigt, CA and Fischbach, MA}, title = {Discovery of Reactive Microbiota-Derived Metabolites that Inhibit Host Proteases.}, journal = {Cell}, volume = {168}, number = {3}, pages = {517-526.e18}, pmid = {28111075}, issn = {1097-4172}, support = {R01 GM104659/GM/NIGMS NIH HHS/United States ; R37 CA087660/CA/NCI NIH HHS/United States ; R01 DK101674/DK/NIDDK NIH HHS/United States ; R01 AT009874/AT/NCCIH NIH HHS/United States ; T32 GM067547/GM/NIGMS NIH HHS/United States ; F32 GM111012/GM/NIGMS NIH HHS/United States ; R01 DK110174/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Bacillus subtilis/genetics ; Bacteria/classification/genetics/*metabolism ; Escherichia coli/genetics ; Feces/microbiology ; *Gastrointestinal Microbiome ; Humans ; *Microbiota ; Peptide Synthases/genetics/*metabolism ; Phylogeny ; Pyrazines/*metabolism ; }, abstract = {The gut microbiota modulate host biology in numerous ways, but little is known about the molecular mediators of these interactions. Previously, we found a widely distributed family of nonribosomal peptide synthetase gene clusters in gut bacteria. Here, by expressing a subset of these clusters in Escherichia coli or Bacillus subtilis, we show that they encode pyrazinones and dihydropyrazinones. At least one of the 47 clusters is present in 88% of the National Institutes of Health Human Microbiome Project (NIH HMP) stool samples, and they are transcribed under conditions of host colonization. We present evidence that the active form of these molecules is the initially released peptide aldehyde, which bears potent protease inhibitory activity and selectively targets a subset of cathepsins in human cell proteomes. Our findings show that an approach combining bioinformatics, synthetic biology, and heterologous gene cluster expression can rapidly expand our knowledge of the metabolic potential of the microbiota while avoiding the challenges of cultivating fastidious commensals.}, }
@article {pmid28096237, year = {2017}, author = {Rajagopala, SV and Vashee, S and Oldfield, LM and Suzuki, Y and Venter, JC and Telenti, A and Nelson, KE}, title = {The Human Microbiome and Cancer.}, journal = {Cancer prevention research (Philadelphia, Pa.)}, volume = {10}, number = {4}, pages = {226-234}, doi = {10.1158/1940-6207.CAPR-16-0249}, pmid = {28096237}, issn = {1940-6215}, mesh = {*Gastrointestinal Microbiome ; Humans ; Neoplasms/*microbiology ; }, abstract = {Recent scientific advances have significantly contributed to our understanding of the complex connection between the microbiome and cancer. Our bodies are continuously exposed to microbial cells, both resident and transient, as well as their byproducts, including toxic metabolites. Circulation of toxic metabolites may contribute to cancer onset or progression at locations distant from where a particular microbe resides. Moreover, microbes may migrate to other locations in the human body and become associated with tumor development. Several case-control metagenomics studies suggest that dysbiosis in the commensal microbiota is also associated with inflammatory disorders and various cancer types throughout the body. Although the microbiome influences carcinogenesis through mechanisms independent of inflammation and immune system, the most recognizable link is between the microbiome and cancer via the immune system, as the resident microbiota plays an essential role in activating, training, and modulating the host immune response. Immunologic dysregulation is likely to provide mechanistic explanations as to how our microbiome influences cancer development and cancer therapies. In this review, we discuss recent developments in understanding the human gut microbiome's relationship with cancer and the feasibility of developing novel cancer diagnostics based on microbiome profiles. Cancer Prev Res; 10(4); 226-34. ©2017 AACR.}, }
@article {pmid28095889, year = {2017}, author = {Hill, CJ and Lynch, DB and Murphy, K and Ulaszewska, M and Jeffery, IB and O'Shea, CA and Watkins, C and Dempsey, E and Mattivi, F and Tuohy, K and Ross, RP and Ryan, CA and O' Toole, PW and Stanton, C}, title = {Evolution of gut microbiota composition from birth to 24 weeks in the INFANTMET Cohort.}, journal = {Microbiome}, volume = {5}, number = {1}, pages = {4}, pmid = {28095889}, issn = {2049-2618}, mesh = {Bacteria/*classification/genetics/isolation &amp; purification ; Breast Feeding ; Cesarean Section ; DNA, Bacterial/genetics ; DNA, Ribosomal/genetics ; Feces/*microbiology ; Female ; Gastrointestinal Microbiome ; Humans ; Infant, Newborn ; Metabolomics/methods ; Phylogeny ; Pregnancy ; Premature Birth/*microbiology ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA/*methods ; Urine/*chemistry ; }, abstract = {BACKGROUND: The gut is the most extensively studied niche of the human microbiome. The aim of this study was to characterise the initial gut microbiota development of a cohort of breastfed infants (n = 192) from 1 to 24 weeks of age.<br><br>METHODS: V4-V5 region 16S rRNA amplicon Illumina sequencing and, in parallel, bacteriological culture. The metabolomic profile of infant urine at 4 weeks of age was also examined by LC-MS.<br><br>RESULTS: Full-term (FT), spontaneous vaginally delivered (SVD) infants' microbiota remained stable at both phylum and genus levels during the 24-week period examined. FT Caesarean section (CS) infants displayed an increased faecal abundance of Firmicutes (p&#x2009;<&#x2009;0.01) and lower abundance of Actinobacteria (p&#x2009;<&#x2009;0.001) after the first week of life compared to FT-SVD infants. FT-CS infants gradually progressed to harbouring a microbiota closely resembling FT-SVD (which remained stable) by week 8 of life, which was maintained at week 24. The gut microbiota of preterm (PT) infants displayed a significantly greater abundance of Proteobacteria compared to FT infants (p&#x2009;<&#x2009;0.001) at week 1. Metabolomic analysis of urine at week 4 indicated PT-CS infants have a functionally different metabolite profile than FT (both CS and SVD) infants. Co-inertia analysis showed co-variation between the urine metabolome and the faecal microbiota of the infants. Tryptophan and tyrosine metabolic pathways, as well as fatty acid and bile acid metabolism, were found to be affected by delivery mode and gestational age.<br><br>CONCLUSIONS: These findings confirm that mode of delivery and gestational age both have significant effects on early neonatal microbiota composition. There is also a significant difference between the metabolite profile of FT and PT infants. Prolonged breastfeeding was shown to have a significant effect on the microbiota composition of FT-CS infants at 24 weeks of age, but interestingly not on that of FT-SVD infants. Twins had more similar microbiota to one another than between two random infants, reflecting the influence of similarities in both host genetics and the environment on the microbiota.&#xfeff;.}, }
@article {pmid28090478, year = {2016}, author = {Varga, C and Kiss, I}, title = {The Human Microbiome: A Public Health Approach.}, journal = {Journal of public health research}, volume = {5}, number = {3}, pages = {764}, pmid = {28090478}, issn = {2279-9028}, }
@article {pmid28081260, year = {2017}, author = {Klughammer, J and Dittrich, M and Blom, J and Mitesser, V and Vogel, U and Frosch, M and Goesmann, A and Müller, T and Schoen, C}, title = {Comparative Genome Sequencing Reveals Within-Host Genetic Changes in Neisseria meningitidis during Invasive Disease.}, journal = {PloS one}, volume = {12}, number = {1}, pages = {e0169892}, pmid = {28081260}, issn = {1932-6203}, mesh = {Cell Line ; *Evolution, Molecular ; Female ; *Genome, Bacterial ; High-Throughput Nucleotide Sequencing ; Host-Pathogen Interactions/*genetics ; Humans ; Male ; Meningococcal Infections/*genetics ; *Mutation ; *Neisseria meningitidis/pathogenicity/physiology ; }, abstract = {Some members of the physiological human microbiome occasionally cause life-threatening disease even in immunocompetent individuals. A prime example of such a commensal pathogen is Neisseria meningitidis, which normally resides in the human nasopharynx but is also a leading cause of sepsis and epidemic meningitis. Using N. meningitidis as model organism, we tested the hypothesis that virulence of commensal pathogens is a consequence of within host evolution and selection of invasive variants due to mutations at contingency genes, a mechanism called phase variation. In line with the hypothesis that phase variation evolved as an adaptation to colonize diverse hosts, computational comparisons of all 27 to date completely sequenced and annotated meningococcal genomes retrieved from public databases showed that contingency genes are indeed enriched for genes involved in host interactions. To assess within-host genetic changes in meningococci, we further used ultra-deep whole-genome sequencing of throat-blood strain pairs isolated from four patients suffering from invasive meningococcal disease. We detected up to three mutations per strain pair, affecting predominantly contingency genes involved in type IV pilus biogenesis. However, there was not a single (set) of mutation(s) that could invariably be found in all four pairs of strains. Phenotypic assays further showed that these genetic changes were generally not associated with increased serum resistance, higher fitness in human blood ex vivo or differences in the interaction with human epithelial and endothelial cells in vitro. In conclusion, we hypothesize that virulence of meningococci results from accidental emergence of invasive variants during carriage and without within host evolution of invasive phenotypes during disease progression in vivo.}, }
@article {pmid28078319, year = {2016}, author = {Sun, J and Kato, I}, title = {Gut microbiota, inflammation and colorectal cancer.}, journal = {Genes &amp; diseases}, volume = {3}, number = {2}, pages = {130-143}, pmid = {28078319}, issn = {2352-4820}, support = {R01 DK105118/DK/NIDDK NIH HHS/United States ; }, abstract = {Although genes contribute to colorectal cancer, the gut microbiota are an important player. Accumulating evidence suggests that chronic infection and the ensuing inflammation contributes to tumor initiation and tumor progression. A variety of bacterial species and tumor-promoting virulence mechanisms have been investigated. Significant advances have been made in understanding the composition and functional capabilities of the gut microbiota and its roles in cancer. In the current review, we discuss the novel roles of microbiota in the progression of colon cancer. Although microbiota technically include organisms other than bacteria e.g., viruses and fungi, this review will primarily focus on bacteria. We summarize epidemiological studies of human microbiome and colon cancer. We discuss the progress in the scientific understanding of the interplay between the gut microbiota, barrier function, and host responses in experimental models. Further, we discuss the potential application in prevention, diagnosis, and therapy of colon cancer by targeting microbiota. We discuss the challenges lie ahead and the future direction in studying gut microbiome in colon cancer to close the gap between the basic sciences and clinical application.}, }
@article {pmid28077565, year = {2017}, author = {Blanco-Míguez, A and Gutiérrez-Jácome, A and Fdez-Riverola, F and Lourenço, A and Sánchez, B}, title = {MAHMI database: a comprehensive MetaHit-based resource for the study of the mechanism of action of the human microbiota.}, journal = {Database : the journal of biological databases and curation}, volume = {2017}, number = {}, pages = {}, pmid = {28077565}, issn = {1758-0463}, mesh = {Autoimmune Diseases/genetics/immunology/microbiology ; *Databases, Protein ; Humans ; Inflammatory Bowel Diseases/genetics/immunology/microbiology ; *Microbiota/genetics/immunology ; *Peptides/genetics/immunology ; }, abstract = {The Mechanism of Action of the Human Microbiome (MAHMI) database is a unique resource that provides comprehensive information about the sequence of potential immunomodulatory and antiproliferative peptides encrypted in the proteins produced by the human gut microbiota. Currently, MAHMI database contains over 300 hundred million peptide entries, with detailed information about peptide sequence, sources and potential bioactivity. The reference peptide data section is curated manually by domain experts. The in silico peptide data section is populated automatically through the systematic processing of publicly available exoproteomes of the human microbiome. Bioactivity prediction is based on the global alignment of the automatically processed peptides with experimentally validated immunomodulatory and antiproliferative peptides, in the reference section. MAHMI provides researchers with a comparative tool for inspecting the potential immunomodulatory or antiproliferative bioactivity of new amino acidic sequences and identifying promising peptides to be further investigated. Moreover, researchers are welcome to submit new experimental evidence on peptide bioactivity, namely, empiric and structural data, as a proactive, expert means to keep the database updated and improve the implemented bioactivity prediction method. Bioactive peptides identified by MAHMI have a huge biotechnological potential, including the manipulation of aberrant immune responses and the design of new functional ingredients/foods based on the genetic sequences of the human microbiome. Hopefully, the resources provided by MAHMI will be useful to those researching gastrointestinal disorders of autoimmune and inflammatory nature, such as Inflammatory Bowel Diseases. MAHMI database is routinely updated and is available free of charge. Database URL: http://mahmi.org/.}, }
@article {pmid28077127, year = {2017}, author = {Chuong, KH and Hwang, DM and Tullis, DE and Waters, VJ and Yau, YC and Guttman, DS and O'Doherty, KC}, title = {Navigating social and ethical challenges of biobanking for human microbiome research.}, journal = {BMC medical ethics}, volume = {18}, number = {1}, pages = {1}, pmid = {28077127}, issn = {1472-6939}, support = {//CIHR/Canada ; }, mesh = {Biological Specimen Banks/*ethics ; Biomedical Research/*ethics ; Canada ; *Confidentiality ; Cystic Fibrosis/microbiology ; *Disclosure ; Ethics, Research ; Humans ; Incidental Findings ; Information Dissemination ; Lung/microbiology ; *Microbiota ; *Privacy ; Public Health ; Public Opinion ; }, abstract = {BACKGROUND: Biobanks are considered to be key infrastructures for research development and have generated a lot of debate about their ethical, legal and social implications (ELSI). While the focus has been on human genomic research, rapid advances in human microbiome research further complicate the debate.<br><br>DISCUSSION: We draw on two cystic fibrosis biobanks in Toronto, Canada, to illustrate our points. The biobanks have been established to facilitate sample and data sharing for research into the link between disease progression and microbial dynamics in the lungs of pediatric and adult patients. We begin by providing an overview of some of the ELSI associated with human microbiome research, particularly on the implications for the broader society. We then discuss ethical considerations regarding the identifiability of samples biobanked for human microbiome research, and examine the issue of return of results and incidental findings. We argue that, for the purposes of research ethics oversight, human microbiome research samples should be treated with the same privacy considerations as human tissues samples. We also suggest that returning individual microbiome-related findings could provide a powerful clinical tool for care management, but highlight the need for a more grounded understanding of contextual factors that may be unique to human microbiome research.<br><br>CONCLUSIONS: We revisit the ELSI of biobanking and consider the impact that human microbiome research might have. Our discussion focuses on identifiability of human microbiome research samples, and return of research results and incidental findings for clinical management.}, }
@article {pmid28076867, year = {2016}, author = {Hua, X and Goedert, JJ and Landi, MT and Shi, J}, title = {Identifying Host Genetic Variants Associated with Microbiome Composition by Testing Multiple Beta Diversity Matrices.}, journal = {Human heredity}, volume = {81}, number = {2}, pages = {117-126}, pmid = {28076867}, issn = {1423-0062}, support = {Z99 CA999999//Intramural NIH HHS/United States ; }, mesh = {Computer Simulation ; Gene Frequency/genetics ; *Genetic Variation ; Genome-Wide Association Study ; Humans ; Lung/microbiology ; Microbiota/*genetics ; Polymorphism, Single Nucleotide/genetics ; }, abstract = {OBJECTIVES: Host genetics have been recently reported to affect human microbiome composition. We previously developed a statistical framework, microbiomeGWAS, to identify host genetic variants associated with microbiome composition by testing a distance matrix. However, statistical power depends on the choice of a microbiome distance matrix. To achieve more robust statistical power, we aim to extend microbiomeGWAS to test the association with many distance matrices, which are defined based on multilevel taxa abundances and phylogenetic information.<br><br>METHODS: The main challenge is to accurately and rapidly evaluate the significance for millions of SNPs. We propose methods for approximating p values by correcting for the multiple testing introduced by testing many distance matrices and by correcting for the skewness and kurtosis of score statistics.<br><br>RESULTS: The accuracy of p value approximation was verified by simulations. We applied our method to a set of 147 lung cancer patients with 16S rRNA microbiome profiles from nonmalignant lung tissues. We show that correcting for skewness and kurtosis eliminated dramatic deviations in the quantile-quantile plot.<br><br>CONCLUSION: We developed computationally efficient methods for identifying host genetic variants associated with microbiome composition by testing many distance matrices. The algorithms are implemented in the package microbiomeGWAS (https://github.com/lsncibb/microbiomeGWAS).}, }
@article {pmid28070463, year = {2017}, author = {Al, K and Sarr, O and Dunlop, K and Gloor, GB and Reid, G and Burton, J and Regnault, TR}, title = {Impact of birth weight and postnatal diet on the gut microbiota of young adult guinea pigs.}, journal = {PeerJ}, volume = {5}, number = {}, pages = {e2840}, pmid = {28070463}, issn = {2167-8359}, abstract = {BACKGROUND: The gastrointestinal tract (GIT) microbiota is essential to metabolic health, and the prevalence of the Western diet (WD) high in fat and sugar is increasing, with evidence highlighting a negative interaction between the GIT and WD, resulting in liver dysfunction. Additionally, an adverse in utero environment such as placental insufficiency resulting in low birth weight (LBW) offspring, contributes to an increased risk of metabolic diseases such as fatty liver infiltration and liver dysfunction in later life. We sought to understand the potential interactive effects of exposure to a WD upon growing LBW offspring. We postulated that LBW offspring when challenged with a poor postnatal diet, would display an altered microbiota and more severe liver metabolic dysfunction.<br><br>METHODS: The fecal microbiota of normal birth weight (NBW) and LBW young guinea pig offspring, weaned onto either a control diet (CD) or WD was determined with 16S rRNA gene next generation sequencing at young adulthood following the early rapid growth phase after weaning. A liver blood chemistry profile was also performed.<br><br>RESULTS: The life-long consumption of WD following weaning into young adulthood resulted in increased total cholesterol, triglycerides and alanine aminotransferase levels in association with an altered GIT microbiota when compared to offspring consuming CD. Neither birth weight nor sex were associated with any significant changes in microbiota alpha diversity, by measuring the Shannon's diversity index. One hundred forty-eight operational taxonomic units were statistically distinct between the diet groups, independent of birth weight. In the WD group, significant decreases were detected in Barnesiella, Methanobrevibacter smithii and relatives of Oscillospira guillermondii, while Butyricimonas and Bacteroides spp. were increased.<br><br>DISCUSSION: These results describe the GIT microbiota in a guinea pig model of LBW and WD associated metabolic syndrome and highlight several WD specific GIT alterations associated with human metabolic disease.}, }
@article {pmid28067829, year = {2017}, author = {D'Argenio, V and Torino, M and Precone, V and Casaburi, G and Esposito, MV and Iaffaldano, L and Malapelle, U and Troncone, G and Coto, I and Cavalcanti, P and De Rosa, G and Salvatore, F and Sacchetti, L}, title = {The Cause of Death of a Child in the 18th Century Solved by Bone Microbiome Typing Using Laser Microdissection and Next Generation Sequencing.}, journal = {International journal of molecular sciences}, volume = {18}, number = {1}, pages = {}, pmid = {28067829}, issn = {1422-0067}, mesh = {Actinobacteria/genetics/isolation &amp; purification ; Bacteroidetes/genetics/isolation &amp; purification ; Bone and Bones/*microbiology ; Cause of Death ; Child ; Firmicutes/genetics/isolation &amp; purification ; Genotype ; *High-Throughput Nucleotide Sequencing ; History, 18th Century ; Humans ; *Laser Capture Microdissection ; Male ; *Microbiota ; Osteomyelitis/history/microbiology ; Proteobacteria/genetics/isolation &amp; purification ; Pseudomonas/genetics/isolation &amp; purification ; Pseudomonas Infections/history/microbiology ; RNA, Ribosomal, 16S/genetics ; }, abstract = {The history of medicine abounds in cases of mysterious deaths, especially by infectious diseases, which were probably unresolved because of the lack of knowledge and of appropriate technology. The aim of this study was to exploit contemporary technologies to try to identify the cause of death of a young boy who died from a putative "infection" at the end of the 18th century, and for whom an extraordinarily well-preserved minute bone fragment was available. After confirming the nature of the sample, we used laser microdissection to select the most "informative" area to be examined. Tissue genotyping indicated male gender, thereby confirming the notary's report. 16S ribosomal RNA sequencing showed that Proteobacteria and Actinobacteria were more abundant than Firmicutes and Bacteroidetes, and that Pseudomonas was the most abundant bacterial genus in the Pseudomonadaceae family. These data suggest that the patient most likely died from Pseudomonas osteomyelitis. This case is an example of how new technological approaches, like laser microdissection and next-generation sequencing, can resolve ancient cases of uncertain etiopathology. Lastly, medical samples may contain a wealth of information that may not be accessible until more sophisticated technology becomes available. Therefore, one may envisage the possibility of systematically storing medical samples for evaluation by future generations.}, }
@article {pmid28066342, year = {2016}, author = {Klymiuk, I and Bambach, I and Patra, V and Trajanoski, S and Wolf, P}, title = {16S Based Microbiome Analysis from Healthy Subjects' Skin Swabs Stored for Different Storage Periods Reveal Phylum to Genus Level Changes.}, journal = {Frontiers in microbiology}, volume = {7}, number = {}, pages = {2012}, pmid = {28066342}, issn = {1664-302X}, abstract = {Microbiome research and improvements in high throughput sequencing technologies revolutionize our current scientific viewpoint. The human associated microbiome is a prominent focus of clinical research. Large cohort studies are often required to investigate the human microbiome composition and its changes in a multitude of human diseases. Reproducible analyses of large cohort samples require standardized protocols in study design, sampling, storage, processing, and data analysis. In particular, the effect of sample storage on actual results is critical for reproducibility. So far, the effect of storage conditions on the results of microbial analysis has been examined for only a few human biological materials (e.g., stool samples). There is a lack of data and information on appropriate storage conditions on other human derived samples, such as skin. Here, we analyzed skin swab samples collected from three different body locations (forearm, V of the chest and back) of eight healthy volunteers. The skin swabs were soaked in sterile buffer and total DNA was isolated after freezing at -80°C for 24 h, 90 or 365 days. Hypervariable regions V1-2 were amplified from total DNA and libraries were sequenced on an Illumina MiSeq desktop sequencer in paired end mode. Data were analyzed using Qiime 1.9.1. Summarizing all body locations per time point, we found no significant differences in alpha diversity and multivariate community analysis among the three time points. Considering body locations separately significant differences in the richness of forearm samples were found between d0 vs. d90 and d90 vs. d365. Significant differences in the relative abundance of major skin genera (Propionibacterium, Streptococcus, Bacteroides, Corynebacterium, and Staphylococcus) were detected in our samples in Bacteroides only among all time points in forearm samples and between d0 vs. d90 and d90 vs. d365 in V of the chest and back samples. Accordingly, significant differences were detected in the ratios of the main phyla Actinobacteria, Firmicutes, and Bacteroidetes: Actinobacteria vs. Bacteroidetes at d0 vs. d90 (p-value = 0.0234), at d0 vs. d365 (p-value = 0.0234) and d90 vs. d365 (p-value = 0.0234) in forearm samples and at d90 vs. d365 in V of the chest (p-value = 0.0234) and back samples (p-value = 0.0234). The ratios of Firmicutes vs. Bacteroidetes showed no significant changes in any of the body locations as well as the ratios of Actinobacteria vs. Firmicutes at any time point. Studies with larger sample sizes are required to verify our results and determine long term storage effects with regard to specific biological questions.}, }
@article {pmid30182357, year = {2017}, author = {Zhu, X and Wang, J and Reyes-Gibby, C and Shete, S}, title = {Correction to: Processing and Analyzing Human Microbiome Data.}, journal = {Methods in molecular biology (Clifton, N.J.)}, volume = {1666}, number = {}, pages = {E1}, doi = {10.1007/978-1-4939-7274-6_32}, pmid = {30182357}, issn = {1940-6029}, abstract = {The original version of this chapter was inadvertently published without including the dbGaP acknowledgment. The updated chapter now contains that information.}, }
@article {pmid29694765, year = {2017}, author = {Krajewska-Włodarczyk, M}, title = {[The gastrointestinal tract microbiom in connective tissue diseases].}, journal = {Przeglad lekarski}, volume = {74}, number = {2}, pages = {84-88}, pmid = {29694765}, issn = {0033-2240}, mesh = {Autoimmune Diseases/microbiology ; Connective Tissue Diseases/etiology/*microbiology ; Dysbiosis/*complications ; *Gastrointestinal Microbiome ; Humans ; }, abstract = {Factors such as genetics, the environment, infections, and the human body microbiota, mainly gastrointestinal tract microbiota may play a role in the pathogenesis of autoimmune disorders. There is an increasing evidence that suggest an association between gastrointestinal tract dysbiosis, and in particular gut dysbiosis, and connective tissue diseases but it still remains unclear whether alterations in the microbiome are a pathogenic cause or an effect of autoimmune disease. Given the strong variability and abundance of microbes living in close relation with human host, it becomes a difficult task to define what should be considered the normal or the favorable microbiome. Further studies are needed to establish how the human microbiome contributes to disease susceptibility, and to characterize the role of microbial diversity in the pathogenesis of connective tissue diseases and their clinical manifestations. The identification of dysbiosis specific for certain connective tissue diseases may help in the development of an individualized management for each patient. This review aims to summarize current data on the role of the gastrointestinal tract microbiome in connective tissue diseases.}, }
@article {pmid28028549, year = {2016}, author = {Lynch, MD and Neufeld, JD}, title = {SSUnique: Detecting Sequence Novelty in Microbiome Surveys.}, journal = {mSystems}, volume = {1}, number = {6}, pages = {}, pmid = {28028549}, issn = {2379-5077}, abstract = {High-throughput sequencing of small-subunit (SSU) rRNA genes has revolutionized understanding of microbial communities and facilitated investigations into ecological dynamics at unprecedented scales. Such extensive SSU rRNA gene sequence libraries, constructed from DNA extracts of environmental or host-associated samples, often contain a substantial proportion of unclassified sequences, many representing organisms with novel taxonomy (taxonomic "blind spots") and potentially unique ecology. Indeed, these novel taxonomic lineages are associated with so-called microbial "dark matter," which is the genomic potential of these lineages. Unfortunately, characterization beyond "unclassified" is challenging due to relatively short read lengths and large data set sizes. Here we demonstrate how mining of phylogenetically novel sequences from microbial ecosystems can be automated using SSUnique, a software pipeline that filters unclassified and/or rare operational taxonomic units (OTUs) from 16S rRNA gene sequence libraries by screening against consensus structural models for SSU rRNA. Phylogenetic position is inferred against a reference data set, and additional characterization of novel clades is also included, such as targeted probe/primer design and mining of assembled metagenomes for genomic context. We show how SSUnique reproduced a previous analysis of phylogenetic novelty from an Arctic tundra soil and demonstrate the recovery of highly novel clades from data sets associated with both the Earth Microbiome Project (EMP) and Human Microbiome Project (HMP). We anticipate that SSUnique will add to the expanding computational toolbox supporting high-throughput sequencing approaches for the study of microbial ecology and phylogeny. IMPORTANCE Extensive SSU rRNA gene sequence libraries, constructed from DNA extracts of environmental or host-associated samples, often contain many unclassified sequences, many representing organisms with novel taxonomy (taxonomic "blind spots") and potentially unique ecology. This novelty is poorly explored in standard workflows, which narrows the breadth and discovery potential of such studies. Here we present the SSUnique analysis pipeline, which will promote the exploration of unclassified diversity in microbiome research and, importantly, enable the discovery of substantial novel taxonomic lineages through the analysis of a large variety of existing data sets.}, }
@article {pmid28019040, year = {2017}, author = {Zhan, X and Tong, X and Zhao, N and Maity, A and Wu, MC and Chen, J}, title = {A small-sample multivariate kernel machine test for microbiome association studies.}, journal = {Genetic epidemiology}, volume = {41}, number = {3}, pages = {210-220}, doi = {10.1002/gepi.22030}, pmid = {28019040}, issn = {1098-2272}, mesh = {Adenomatous Polyposis Coli/*genetics/microbiology ; Case-Control Studies ; Computer Simulation ; *Genetic Association Studies ; Genetic Markers/*genetics ; High-Throughput Nucleotide Sequencing ; Humans ; Microbiota/*genetics ; *Models, Genetic ; Mucous Membrane/microbiology ; Phylogeny ; Polymorphism, Single Nucleotide/*genetics ; Sample Size ; }, abstract = {High-throughput sequencing technologies have enabled large-scale studies of the role of the human microbiome in health conditions and diseases. Microbial community level association test, as a critical step to establish the connection between overall microbiome composition and an outcome of interest, has now been routinely performed in many studies. However, current microbiome association tests all focus on a single outcome. It has become increasingly common for a microbiome study to collect multiple, possibly related, outcomes to maximize the power of discovery. As these outcomes may share common mechanisms, jointly analyzing these outcomes can amplify the association signal and improve statistical power to detect potential associations. We propose the multivariate microbiome regression-based kernel association test (MMiRKAT) for testing association between multiple continuous outcomes and overall microbiome composition, where the kernel used in MMiRKAT is based on Bray-Curtis or UniFrac distance. MMiRKAT directly regresses all outcomes on the microbiome profiles via a semiparametric kernel machine regression framework, which allows for covariate adjustment and evaluates the association via a variance-component score test. Because most of the current microbiome studies have small sample sizes, a novel small-sample correction procedure is implemented in MMiRKAT to correct for the conservativeness of the association test when the sample size is small or moderate. The proposed method is assessed via simulation studies and an application to a real data set examining the association between host gene expression and mucosal microbiome composition. We demonstrate that MMiRKAT is more powerful than large sample based multivariate kernel association test, while controlling the type I error. A free implementation of MMiRKAT in R language is available at http://research.fhcrc.org/wu/en.html.}, }
@article {pmid28005908, year = {2016}, author = {Johnson, HR and Trinidad, DD and Guzman, S and Khan, Z and Parziale, JV and DeBruyn, JM and Lents, NH}, title = {A Machine Learning Approach for Using the Postmortem Skin Microbiome to Estimate the Postmortem Interval.}, journal = {PloS one}, volume = {11}, number = {12}, pages = {e0167370}, pmid = {28005908}, issn = {1932-6203}, mesh = {Bacteria/genetics/isolation &amp; purification ; Cadaver ; DNA, Bacterial/genetics/metabolism ; Forensic Pathology ; Humans ; Machine Learning ; *Microbiota ; Postmortem Changes ; Skin/*microbiology ; Time Factors ; }, abstract = {Research on the human microbiome, the microbiota that live in, on, and around the human person, has revolutionized our understanding of the complex interactions between microbial life and human health and disease. The microbiome may also provide a valuable tool in forensic death investigations by helping to reveal the postmortem interval (PMI) of a decedent that is discovered after an unknown amount of time since death. Current methods of estimating PMI for cadavers discovered in uncontrolled, unstudied environments have substantial limitations, some of which may be overcome through the use of microbial indicators. In this project, we sampled the microbiomes of decomposing human cadavers, focusing on the skin microbiota found in the nasal and ear canals. We then developed several models of statistical regression to establish an algorithm for predicting the PMI of microbial samples. We found that the complete data set, rather than a curated list of indicator species, was preferred for training the regressor. We further found that genus and family, rather than species, are the most informative taxonomic levels. Finally, we developed a k-nearest- neighbor regressor, tuned with the entire data set from all nasal and ear samples, that predicts the PMI of unknown samples with an average error of ±55 accumulated degree days (ADD). This study outlines a machine learning approach for the use of necrobiome data in the prediction of the PMI and thereby provides a successful proof-of- concept that skin microbiota is a promising tool in forensic death investigations.}, }
@article {pmid28005526, year = {2017}, author = {Yoon, SH and Ha, SM and Kwon, S and Lim, J and Kim, Y and Seo, H and Chun, J}, title = {Introducing EzBioCloud: a taxonomically united database of 16S rRNA gene sequences and whole-genome assemblies.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {67}, number = {5}, pages = {1613-1617}, pmid = {28005526}, issn = {1466-5034}, mesh = {Archaea/*classification ; Bacteria/*classification ; Base Composition ; Computational Biology ; *Databases, Nucleic Acid ; Genomics ; Humans ; Microbiota ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; }, abstract = {The recent advent of DNA sequencing technologies facilitates the use of genome sequencing data that provide means for more informative and precise classification and identification of members of the Bacteria and Archaea. Because the current species definition is based on the comparison of genome sequences between type and other strains in a given species, building a genome database with correct taxonomic information is of paramount need to enhance our efforts in exploring prokaryotic diversity and discovering novel species as well as for routine identifications. Here we introduce an integrated database, called EzBioCloud, that holds the taxonomic hierarchy of the Bacteria and Archaea, which is represented by quality-controlled 16S rRNA gene and genome sequences. Whole-genome assemblies in the NCBI Assembly Database were screened for low quality and subjected to a composite identification bioinformatics pipeline that employs gene-based searches followed by the calculation of average nucleotide identity. As a result, the database is made of 61 700 species/phylotypes, including 13 132 with validly published names, and 62 362 whole-genome assemblies that were identified taxonomically at the genus, species and subspecies levels. Genomic properties, such as genome size and DNA G+C content, and the occurrence in human microbiome data were calculated for each genus or higher taxa. This united database of taxonomy, 16S rRNA gene and genome sequences, with accompanying bioinformatics tools, should accelerate genome-based classification and identification of members of the Bacteria and Archaea. The database and related search tools are available at www.ezbiocloud.net/.}, }
@article {pmid28000336, year = {2017}, author = {Cao, HT and Gibson, TE and Bashan, A and Liu, YY}, title = {Inferring human microbial dynamics from temporal metagenomics data: Pitfalls and lessons.}, journal = {BioEssays : news and reviews in molecular, cellular and developmental biology}, volume = {39}, number = {2}, pages = {}, doi = {10.1002/bies.201600188}, pmid = {28000336}, issn = {1521-1878}, mesh = {Bacteria/*genetics ; *Biota ; Gastrointestinal Microbiome/*genetics ; Humans ; Metagenomics/*methods ; Microbial Interactions ; *Models, Biological ; }, abstract = {The human gut microbiota is a very complex and dynamic ecosystem that plays a crucial role in health and well-being. Inferring microbial community structure and dynamics directly from time-resolved metagenomics data is key to understanding the community ecology and predicting its temporal behavior. Many methods have been proposed to perform the inference. Yet, as we point out in this review, there are several pitfalls along the way. Indeed, the uninformative temporal measurements and the compositional nature of the relative abundance data raise serious challenges in inference. Moreover, the inference results can be largely distorted when only focusing on highly abundant species by ignoring or grouping low-abundance species. Finally, the implicit assumptions in various regularization methods may not reflect reality. Those issues have to be seriously considered in ecological modeling of human gut microbiota.}, }
@article {pmid27997976, year = {2016}, author = {Monsour, HP and Quigley, EM}, title = {The Microbiome: What Will the Future Hold?.}, journal = {Seminars in liver disease}, volume = {36}, number = {4}, pages = {354-359}, doi = {10.1055/s-0036-1594009}, pmid = {27997976}, issn = {1098-8971}, mesh = {Anti-Bacterial Agents/therapeutic use ; Fecal Microbiota Transplantation/trends ; Forecasting ; Gastrointestinal Tract/*microbiology ; Humans ; Liver Diseases/*microbiology ; Meta-Analysis as Topic ; *Microbiota ; Prebiotics ; Probiotics/therapeutic use ; Treatment Outcome ; }, abstract = {Current research on the human microbiome has opened our eyes to the intimate relationship that we have with the bacteria that populate our gastrointestinal tract and its potential relationship to health and disease. To date, clinical research on the microbiome has identified intriguing associations between an altered microbiome and disease states, but proven therapeutic applications have been very limited. The ingestion of prebiotics, probiotics, and/or synbiotics is appealing to the general public and has significant commercial value, but as yet, solid evidence for clinical efficacy in liver disease has been lacking due, in large part, to the paucity of high-quality clinical trials. On the other hand, the resounding success of fecal microbiota transplantation in Clostridium difficile infection has opened our eyes to the real potential of "pharmabiotics" and may well provide an intriguing template for the development of novel approaches to modulate the microbiome and its interactions with the host and thereby treat and/or prevent disease states. We will attempt to examine the current state of microbiome therapeutics and predict how these approaches might fit into the management of liver diseases in the future.}, }
@article {pmid27989793, year = {2017}, author = {Mendes-Soares, H and Chia, N}, title = {Community metabolic modeling approaches to understanding the gut microbiome: Bridging biochemistry and ecology.}, journal = {Free radical biology &amp; medicine}, volume = {105}, number = {}, pages = {102-109}, pmid = {27989793}, issn = {1873-4596}, support = {P30 DK084567/DK/NIDDK NIH HHS/United States ; R01 CA179243/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; *Gastrointestinal Microbiome ; Gastrointestinal Tract/microbiology ; Humans ; *Metabolic Networks and Pathways ; Microbial Interactions ; Models, Biological ; }, abstract = {Interest in the human microbiome is at an all time high. The number of human microbiome studies is growing exponentially, as are reported associations between microbial communities and disease. However, we have not been able to translate the ever-growing amount of microbiome sequence data into better health. To do this, we need a practical means of transforming a disease-associated microbiome into a health-associated microbiome. This will require a framework that can be used to generate predictions about community dynamics within the microbiome under different conditions, predictions that can be tested and validated. In this review, using the gut microbiome to illustrate, we describe two classes of model that are currently being used to generate predictions about microbial community dynamics: ecological models and metabolic models. We outline the strengths and weaknesses of each approach and discuss the insights into the gut microbiome that have emerged from modeling thus far. We then argue that the two approaches can be combined to yield a community metabolic model, which will supply the framework needed to move from high-throughput omics data to testable predictions about how prebiotic, probiotic, and nutritional interventions affect the microbiome. We are confident that with a suitable model, researchers and clinicians will be able to harness the stream of sequence data and begin designing strategies to make targeted alterations to the microbiome and improve health.}, }
@article {pmid27980489, year = {2016}, author = {Bland, J}, title = {Intestinal Microbiome, Akkermansia muciniphila, and Medical Nutrition Therapy.}, journal = {Integrative medicine (Encinitas, Calif.)}, volume = {15}, number = {5}, pages = {14-16}, pmid = {27980489}, issn = {1546-993X}, abstract = {The gastrointestinal microbiome has become a topic of great interest in medicine in recent years. Genomic sequencing can now be done at a fraction of the cost of a few years ago, and this has allowed for the development and compilation of an extensive amount of data related to the species diversity of the human gastrointestinal microbiome.1 Studies have demonstrated that the intestinal microbiome is sensitive to the composition of the diet.2 It is also recognized that the composition of the microbiome can be altered rapidly in response to dietary changes, stress, chemical exposure, and exercise.3 Both the expanded understanding of the composition of the human microbiome and the ability to measure it through genomic analysis of the stool have resulted in clinicians frequently wanting to know what actionable conclusions can be taken away from an analysis of the gastrointestinal microbiome.}, }
@article {pmid27975077, year = {2016}, author = {Boughner, LA and Singh, P}, title = {Microbial Ecology: Where are we now?.}, journal = {Postdoc journal : a journal of postdoctoral research and postdoctoral affairs}, volume = {4}, number = {11}, pages = {3-17}, pmid = {27975077}, issn = {2328-9791}, support = {U19 AI090872/AI/NIAID NIH HHS/United States ; }, abstract = {Conventional microbiological methods have been readily taken over by newer molecular techniques due to the ease of use, reproducibility, sensitivity and speed of working with nucleic acids. These tools allow high throughput analysis of complex and diverse microbial communities, such as those in soil, freshwater, saltwater, or the microbiota living in collaboration with a host organism (plant, mouse, human, etc). For instance, these methods have been robustly used for characterizing the plant (rhizosphere), animal and human microbiome specifically the complex intestinal microbiota. The human body has been referred to as the Superorganism since microbial genes are more numerous than the number of human genes and are essential to the health of the host. In this review we provide an overview of the Next Generation tools currently available to study microbial ecology, along with their limitations and advantages.}, }
@article {pmid27920774, year = {2016}, author = {Nielsen, CK and Kjems, J and Mygind, T and Snabe, T and Meyer, RL}, title = {Effects of Tween 80 on Growth and Biofilm Formation in Laboratory Media.}, journal = {Frontiers in microbiology}, volume = {7}, number = {}, pages = {1878}, pmid = {27920774}, issn = {1664-302X}, abstract = {Tween 80 is a widely used non-ionic emulsifier that is added to cosmetics, pharmaceuticals, and foods. Because of its widespread use we need to understand how it affects bacteria on our skin, in our gut, and in food products. The aim of this study is to investigate how Tween 80 affects the growth and antimicrobial susceptibility of Staphylococcus aureus, Listeria monocytogenes, and Pseudomonas fluorescens, which are common causes of spoilage and foodborne illnesses. Addition of 0.1% Tween 80 to laboratory growth media increased the growth rate of planktonic S. aureus batch cultures, and it also increased the total biomass when S. aureus was grown as biofilms. In contrast, Tween 80 had no effect on batch cultures of L. monocytogenes, it slowed the growth rate of P. fluorescens, and it led to formation of less biofilm by both L. monocytogenes and P. fluorescens. Furthermore, Tween 80 lowered the antibacterial efficacy of two hydrophobic antimicrobials: rifampicin and the essential oil isoeugenol. Our findings underline the importance of documenting indirect effects of emulsifiers when studying the efficacy of hydrophobic antimicrobials that are dispersed in solution by emulsification, or when antimicrobials are applied in food matrixes that include emulsifiers. Furthermore, the species-specific effects on microbial growth suggests that Tween 80 in cosmetics and food products could affect the composition of skin and gut microbiota, and the effect of emulsifiers on the human microbiome should therefore be explored to uncover potential health effects.}, }
@article {pmid27916477, year = {2016}, author = {Devlin, AS and Marcobal, A and Dodd, D and Nayfach, S and Plummer, N and Meyer, T and Pollard, KS and Sonnenburg, JL and Fischbach, MA}, title = {Modulation of a Circulating Uremic Solute via Rational Genetic Manipulation of the Gut Microbiota.}, journal = {Cell host &amp; microbe}, volume = {20}, number = {6}, pages = {709-715}, pmid = {27916477}, issn = {1934-6069}, support = {R01 DK085025/DK/NIDDK NIH HHS/United States ; R01 DK101674/DK/NIDDK NIH HHS/United States ; T32 GM067547/GM/NIGMS NIH HHS/United States ; }, mesh = {Animal Feed ; Animals ; Bacteria/drug effects/enzymology/genetics/metabolism ; Bacteroides/enzymology/genetics ; Diet ; Disease Models, Animal ; Disease Progression ; Gastrointestinal Microbiome/genetics/*physiology ; Gastrointestinal Tract/*microbiology ; Genetic Engineering ; Germ-Free Life/drug effects ; Humans ; Indican/*metabolism/*toxicity ; Indoles/metabolism ; Metagenome ; Mice ; Microbiota/genetics ; Renal Insufficiency, Chronic ; Toxins, Biological/biosynthesis/urine ; Tryptophan/metabolism ; Tryptophanase/metabolism ; }, abstract = {Renal disease is growing in prevalence and has striking co-morbidities with metabolic and cardiovascular disease. Indoxyl sulfate (IS) is a toxin that accumulates in plasma when kidney function declines and contributes to the progression of chronic kidney disease. IS derives exclusively from the gut microbiota. Bacterial tryptophanases convert tryptophan to indole, which is absorbed and modified by the host to produce IS. Here, we identify a widely distributed family of tryptophanases in the gut commensal Bacteroides and find that deleting this gene eliminates the production of indole in vitro. By altering the status or abundance of the Bacteroides tryptophanase, we can modulate IS levels in gnotobiotic mice and in the background of a conventional murine gut community. Our results demonstrate that it is possible to control host IS levels by targeting the microbiota and suggest a possible strategy for treating renal disease.}, }
@article {pmid27912057, year = {2016}, author = {Sampson, TR and Debelius, JW and Thron, T and Janssen, S and Shastri, GG and Ilhan, ZE and Challis, C and Schretter, CE and Rocha, S and Gradinaru, V and Chesselet, MF and Keshavarzian, A and Shannon, KM and Krajmalnik-Brown, R and Wittung-Stafshede, P and Knight, R and Mazmanian, SK}, title = {Gut Microbiota Regulate Motor Deficits and Neuroinflammation in a Model of Parkinson's Disease.}, journal = {Cell}, volume = {167}, number = {6}, pages = {1469-1480.e12}, pmid = {27912057}, issn = {1097-4172}, support = {R01 NS085910/NS/NINDS NIH HHS/United States ; }, mesh = {Animals ; Brain/pathology ; Dysbiosis/pathology ; Fatty Acids/metabolism ; Gastrointestinal Microbiome ; Gastrointestinal Tract/microbiology/physiopathology ; Humans ; Inflammation/metabolism/microbiology/pathology ; Mice ; Microglia/pathology ; Parkinson Disease/metabolism/*microbiology/*pathology/physiopathology ; alpha-Synuclein/metabolism ; }, abstract = {The intestinal microbiota influence neurodevelopment, modulate behavior, and contribute to neurological disorders. However, a functional link between gut bacteria and neurodegenerative diseases remains unexplored. Synucleinopathies are characterized by aggregation of the protein α-synuclein (αSyn), often resulting in motor dysfunction as exemplified by Parkinson's disease (PD). Using mice that overexpress αSyn, we report herein that gut microbiota are required for motor deficits, microglia activation, and αSyn pathology. Antibiotic treatment ameliorates, while microbial re-colonization promotes, pathophysiology in adult animals, suggesting that postnatal signaling between the gut and the brain modulates disease. Indeed, oral administration of specific microbial metabolites to germ-free mice promotes neuroinflammation and motor symptoms. Remarkably, colonization of αSyn-overexpressing mice with microbiota from PD-affected patients enhances physical impairments compared to microbiota transplants from healthy human donors. These findings reveal that gut bacteria regulate movement disorders in mice and suggest that alterations in the human microbiome represent a risk factor for PD.}, }
@article {pmid27904880, year = {2016}, author = {Bik, HM and Maritz, JM and Luong, A and Shin, H and Dominguez-Bello, MG and Carlton, JM}, title = {Microbial Community Patterns Associated with Automated Teller Machine Keypads in New York City.}, journal = {mSphere}, volume = {1}, number = {6}, pages = {}, pmid = {27904880}, issn = {2379-5042}, abstract = {In densely populated urban environments, the distribution of microbes and the drivers of microbial community assemblages are not well understood. In sprawling metropolitan habitats, the "urban microbiome" may represent a mix of human-associated and environmental taxa. Here we carried out a baseline study of automated teller machine (ATM) keypads in New York City (NYC). Our goal was to describe the biodiversity and biogeography of both prokaryotic and eukaryotic microbes in an urban setting while assessing the potential source of microbial assemblages on ATM keypads. Microbial swab samples were collected from three boroughs (Manhattan, Queens, and Brooklyn) during June and July 2014, followed by generation of Illumina MiSeq datasets for bacterial (16S rRNA) and eukaryotic (18S rRNA) marker genes. Downstream analysis was carried out in the QIIME pipeline, in conjunction with neighborhood metadata (ethnicity, population, age groups) from the NYC Open Data portal. Neither the 16S nor 18S rRNA datasets showed any clustering patterns related to geography or neighborhood demographics. Bacterial assemblages on ATM keypads were dominated by taxonomic groups known to be associated with human skin communities (Actinobacteria, Bacteroides, Firmicutes, and Proteobacteria), although SourceTracker analysis was unable to identify the source habitat for the majority of taxa. Eukaryotic assemblages were dominated by fungal taxa as well as by a low-diversity protist community containing both free-living and potentially pathogenic taxa (Toxoplasma, Trichomonas). Our results suggest that ATM keypads amalgamate microbial assemblages from different sources, including the human microbiome, eukaryotic food species, and potentially novel extremophilic taxa adapted to air or surfaces in the built environment. DNA obtained from ATM keypads may thus provide a record of both human behavior and environmental sources of microbes. IMPORTANCE Automated teller machine (ATM) keypads represent a specific and unexplored microhabitat for microbial communities. Although the number of built environment and urban microbial ecology studies has expanded greatly in recent years, the majority of research to date has focused on mass transit systems, city soils, and plumbing and ventilation systems in buildings. ATM surfaces, potentially retaining microbial signatures of human inhabitants, including both commensal taxa and pathogens, are interesting from both a biodiversity perspective and a public health perspective. By focusing on ATM keypads in different geographic areas of New York City with distinct population demographics, we aimed to characterize the diversity and distribution of both prokaryotic and eukaryotic microbes, thus making a unique contribution to the growing body of work focused on the "urban microbiome." In New York City, the surface area of urban surfaces in Manhattan far exceeds the geographic area of the island itself. We have only just begun to describe the vast array of microbial taxa that are likely to be present across diverse types of urban habitats.}, }
@article {pmid27899809, year = {2017}, author = {Mueller, NT and Mao, G and Bennet, WL and Hourigan, SK and Dominguez-Bello, MG and Appel, LJ and Wang, X}, title = {Does vaginal delivery mitigate or strengthen the intergenerational association of overweight and obesity? Findings from the Boston Birth Cohort.}, journal = {International journal of obesity (2005)}, volume = {41}, number = {4}, pages = {497-501}, pmid = {27899809}, issn = {1476-5497}, support = {R21 HD066471/HD/NICHD NIH HHS/United States ; U01 AI090727/AI/NIAID NIH HHS/United States ; R01 HD041702/HD/NICHD NIH HHS/United States ; R21 AI079872/AI/NIAID NIH HHS/United States ; R21 HD085556/HD/NICHD NIH HHS/United States ; R21 ES011666/ES/NIEHS NIH HHS/United States ; R01 HD086013/HD/NICHD NIH HHS/United States ; }, mesh = {Adult ; Age of Onset ; Birth Weight ; Body Mass Index ; Boston/epidemiology ; Cesarean Section/adverse effects/*statistics &amp; numerical data ; Child ; Child, Preschool ; Delivery, Obstetric/*statistics &amp; numerical data ; Female ; Follow-Up Studies ; Humans ; Infant, Newborn ; Male ; Microbiota/*immunology ; *Mothers ; Pediatric Obesity/epidemiology/etiology/*immunology ; Pregnancy ; Prospective Studies ; Risk Factors ; Vagina/*microbiology ; }, abstract = {BACKGROUND/OBJECTIVES: The intergenerational association of obesity may be driven by mother-to-newborn transmission of microbiota at birth. Yet cesarean delivery circumvents newborn acquisition of vaginal microbiota, and has been associated with greater childhood adiposity. Here we examined the independent and joint associations of maternal pre-pregnancy body mass index (BMI; kg m[-2]) and delivery mode with childhood overweight or obesity.<br><br>SUBJECTS/METHODS: We prospectively followed 1441 racially and ethnically diverse mother-child dyads in the Boston Birth Cohort until age 5 years (range: 2.0-8.0 years). We used logistic regression to examine the independent and joint associations of delivery mode (cesarean and vaginal delivery) and pre-pregnancy BMI with childhood overweight or obesity (age-sex-specific BMI &#x2a7e;85th percentile).<br><br>RESULTS: Of 1441 mothers, 961 delivered vaginally and 480 by cesarean. Compared with vaginally delivered children, cesarean delivered children had 1.4 (95% confidence interval (CI) 1.1-1.8) times greater odds of becoming overweight or obese in childhood, after adjustment for maternal age at delivery, race/ethnicity, education, air pollution exposure, pre-pregnancy BMI, pregnancy weight gain and birth weight. Compared with children born vaginally to normal weight mothers, after multivariable adjustment, odds of childhood overweight or obesity were highest in children born by cesarean delivery to obese mothers (odds ratio (OR): 2.8; 95% CI: 1.9-4.1), followed by children born by cesarean delivery to overweight mothers (OR: 2.2; 95% CI: 1.5-3.2), then children born vaginally to obese mothers (OR: 1.8; 95% CI: 1.3-2.6) and finally children born vaginally to overweight mothers (OR: 1.7; 95% CI: 1.2-2.3).<br><br>CONCLUSIONS: In our racially and ethnically diverse cohort, cesarean delivery and pre-pregnancy overweight and obesity were associated with childhood overweight or obesity. Needed now are prospective studies that integrate measures of the maternal and infant microbiome, and other potentially explanatory covariates, to elucidate the mechanisms driving this association and to explore whether exposure to vaginal microbiota in cesarean delivered newborns may be an innovative strategy to combat the intergenerational cycle of obesity.}, }
@article {pmid27884206, year = {2016}, author = {Thorsen, J and Brejnrod, A and Mortensen, M and Rasmussen, MA and Stokholm, J and Al-Soud, WA and Sørensen, S and Bisgaard, H and Waage, J}, title = {Large-scale benchmarking reveals false discoveries and count transformation sensitivity in 16S rRNA gene amplicon data analysis methods used in microbiome studies.}, journal = {Microbiome}, volume = {4}, number = {1}, pages = {62}, pmid = {27884206}, issn = {2049-2618}, mesh = {Bacteria/*classification/*genetics ; Base Sequence ; *Benchmarking ; Case-Control Studies ; Computational Biology/methods ; False Positive Reactions ; High-Throughput Nucleotide Sequencing/*methods ; Humans ; Microbiota/*genetics ; RNA, Ribosomal, 16S/*genetics ; Sequence Analysis, RNA/methods ; }, abstract = {BACKGROUND: There is an immense scientific interest in the human microbiome and its effects on human physiology, health, and disease. A common approach for examining bacterial communities is high-throughput sequencing of 16S rRNA gene hypervariable regions, aggregating sequence-similar amplicons into operational taxonomic units (OTUs). Strategies for detecting differential relative abundance of OTUs between sample conditions include classical statistical approaches as well as a plethora of newer methods, many borrowing from the related field of RNA-seq analysis. This effort is complicated by unique data characteristics, including sparsity, sequencing depth variation, and nonconformity of read counts to theoretical distributions, which is often exacerbated by exploratory and/or unbalanced study designs. Here, we assess the robustness of available methods for (1) inference in differential relative abundance analysis and (2) beta-diversity-based sample separation, using a rigorous benchmarking framework based on large clinical 16S microbiome datasets from different sources.<br><br>RESULTS: Running more than 380,000 full differential relative abundance tests on real datasets with permuted case/control assignments and in silico-spiked OTUs, we identify large differences in method performance on a range of parameters, including false positive rates, sensitivity to sparsity and case/control balances, and spike-in retrieval rate. In large datasets, methods with the highest false positive rates also tend to have the best detection power. For beta-diversity-based sample separation, we show that library size normalization has very little effect and that the distance metric is the most important factor in terms of separation power.<br><br>CONCLUSIONS: Our results, generalizable to datasets from different sequencing platforms, demonstrate how the choice of method considerably affects analysis outcome. Here, we give recommendations for tools that exhibit low false positive rates, have good retrieval power across effect sizes and case/control proportions, and have low sparsity bias. Result output from some commonly used methods should be interpreted with caution. We provide an easily extensible framework for benchmarking of new methods and future microbiome datasets.}, }
@article {pmid27871802, year = {2017}, author = {Severance, EG and Gressitt, KL and Stallings, CR and Katsafanas, E and Schweinfurth, LA and Savage, CLG and Adamos, MB and Sweeney, KM and Origoni, AE and Khushalani, S and Dickerson, FB and Yolken, RH}, title = {Probiotic normalization of Candida albicans in schizophrenia: A randomized, placebo-controlled, longitudinal pilot study.}, journal = {Brain, behavior, and immunity}, volume = {62}, number = {}, pages = {41-45}, pmid = {27871802}, issn = {1090-2139}, support = {P50 MH094268/MH/NIMH NIH HHS/United States ; }, mesh = {Adolescent ; Adult ; Aged ; Antibodies, Bacterial/*isolation &amp; purification ; Candida albicans/*immunology ; Female ; Gastrointestinal Microbiome/*drug effects ; Gastrointestinal Tract/*microbiology ; Humans ; Longitudinal Studies ; Male ; Middle Aged ; Pilot Projects ; Probiotics/*administration &amp; dosage ; Schizophrenia/*microbiology ; Treatment Outcome ; Young Adult ; }, abstract = {The molecules and pathways of the gut-brain axis represent new targets for developing methods to diagnose and treat psychiatric disorders. Manipulation of the gut microbiome with probiotics may be a therapeutic strategy with the potential to relieve gastrointestinal (GI) comorbidities and improve psychiatric symptoms. Candida albicans and Saccharomyces cerevisiae, commensal yeast species, can be imbalanced in the unhealthy human microbiome, and these fungal exposures were previously found elevated in schizophrenia. In a longitudinal, double-blind, placebo-controlled, pilot investigation of 56 outpatients with schizophrenia, we examined the impact of probiotic treatment on yeast antibody levels, and the relationship between treatment and antibody levels on bowel discomfort and psychiatric symptoms. We found that probiotic treatment significantly reduced C. albicans antibodies over the 14-week study period in males, but not in females. Antibody levels of S. cerevisiae were not altered in either treatment group. The highest levels of bowel discomfort over time occurred in C. albicans-seropositive males receiving the placebo. We observed trends towards improvement in positive psychiatric symptoms in males treated with probiotics who were seronegative for C. albicans. Results from this pilot study hint at an association of C. albicans seropositivity with worse positive psychiatric symptoms, which was confirmed in a larger cohort of 384 males with schizophrenia. In conclusion, the administration of probiotics may help normalize C. albicans antibody levels and C. albicans-associated gut discomfort in many male individuals. Studies with larger sample sizes are warranted to address the role of probiotics in correcting C. albicans-associated psychiatric symptoms.}, }
@article {pmid27869143, year = {2016}, author = {Liu, L and Hao, T and Xie, Z and Horsman, GP and Chen, Y}, title = {Genome mining unveils widespread natural product biosynthetic capacity in human oral microbe Streptococcus mutans.}, journal = {Scientific reports}, volume = {6}, number = {}, pages = {37479}, pmid = {27869143}, issn = {2045-2322}, mesh = {Amino Acid Sequence ; Bacteriocins/chemistry/pharmacology ; Biological Products/*metabolism/pharmacology ; *Biosynthetic Pathways/drug effects/genetics ; *Data Mining ; Genes, Bacterial ; *Genomics ; Humans ; Mouth/*microbiology ; Multigene Family ; Phylogeny ; Sequence Alignment ; Streptococcus mutans/drug effects/*genetics ; Tenuazonic Acid/analogs &amp; derivatives/chemistry/pharmacology ; }, abstract = {Streptococcus mutans is a major pathogen causing human dental caries. As a Gram-positive bacterium with a small genome (about 2 Mb) it is considered a poor source of natural products. Due to a recent explosion in genomic data available for S. mutans strains, we were motivated to explore the natural product production potential of this organism. Bioinformatic characterization of 169 publically available genomes of S. mutans from human dental caries revealed a surprisingly rich source of natural product biosynthetic gene clusters. Anti-SMASH analysis identified one nonribosomal peptide synthetase (NRPS) gene cluster, seven polyketide synthase (PKS) gene clusters and 136 hybrid PKS/NRPS gene clusters. In addition, 211 ribosomally synthesized and post-translationally modified peptides (RiPPs) clusters and 615 bacteriocin precursors were identified by a combined analysis using BAGEL and anti-SMASH. S. mutans harbors a rich and diverse natural product genetic capacity, which underscores the importance of probing the human microbiome and revisiting species that have traditionally been overlooked as "poor" sources of natural products.}, }
@article {pmid27858010, year = {2016}, author = {Adams, M and Stringer, T and de Kock, C and Smith, PJ and Land, KM and Liu, N and Tam, C and Cheng, LW and Njoroge, M and Chibale, K and Smith, GS}, title = {Bioisosteric ferrocenyl-containing quinolines with antiplasmodial and antitrichomonal properties.}, journal = {Dalton transactions (Cambridge, England : 2003)}, volume = {45}, number = {47}, pages = {19086-19095}, doi = {10.1039/c6dt03175g}, pmid = {27858010}, issn = {1477-9234}, mesh = {Animals ; Antimalarials/*chemical synthesis/chemistry/pharmacology ; Antitrichomonal Agents/*chemical synthesis/chemistry/pharmacology ; CHO Cells ; Cell Survival/drug effects ; Cricetulus ; Drug Design ; Ferrous Compounds/*chemical synthesis/chemistry/pharmacology ; Plasmodium falciparum/drug effects ; Quinolines/*chemical synthesis/chemistry/pharmacology ; Trichomonas vaginalis/drug effects ; }, abstract = {Bioisosteric ferrocenyl-containing quinolines and ferrocenylamines containing organosilanes and their carbon analogues, were prepared and fully characterised. The molecular structures of two ferrocenyl-containing quinolines, determined using single-crystal X-ray diffraction, revealed that the compounds crystallise in a folded conformation. The compounds were screened for their antiplasmodial activity against the chloroquine-sensitive (NF54) and CQ-resistant (Dd2) strains of P. falciparum, as well as for their cytotoxicity against Chinese Hamster Ovarian (CHO) cells. The ferrocenyl-containing quinolines displayed activities in the low nanomolar range (6-36 nM), and showed selectivity towards parasites. β-Haematin inhibition assays suggest that the compounds may in part act via the inhibition of haemozoin formation, while microsomal metabolic stability studies reveal that the ferrocenyl-containing quinolines are rapidly metabolised in liver microsomes. Further, antitrichomonal screening against the metronidazole-sensitive (G3) strain of the mucosal pathogen T. vaginalis revealed that the quinoline-based compounds displayed superior parasite growth inhibition when compared to the ferrocenylamines. The library was also tested E. coli and on Lactobacilli spp. found as part of the normal flora of the human microbiome and no effect on growth in vitro was observed, supporting the observation that these compounds are specific for eukaryotic pathogens.}, }
@article {pmid27832586, year = {2016}, author = {Blaser, MJ and Dominguez-Bello, MG}, title = {The Human Microbiome before Birth.}, journal = {Cell host &amp; microbe}, volume = {20}, number = {5}, pages = {558-560}, doi = {10.1016/j.chom.2016.10.014}, pmid = {27832586}, issn = {1934-6069}, support = {R01 DK090989/DK/NIDDK NIH HHS/United States ; }, mesh = {Female ; Fetus/*microbiology ; Humans ; *Microbiota ; Pregnancy ; }, abstract = {The conservation of the microbiota within humans and other hominids suggests an ancient assembly that has been selected to optimize host fitness. Pregnancy induces changes in the maternal microbiome just before the intergenerational hand-off of the microbiota. Interventions, including peri-partum antibiotics and Cesarean sections, may have unintended effects on babies.}, }
@article {pmid27822543, year = {2016}, author = {Hyde, ER and Navas-Molina, JA and Song, SJ and Kueneman, JG and Ackermann, G and Cardona, C and Humphrey, G and Boyer, D and Weaver, T and Mendelson, JR and McKenzie, VJ and Gilbert, JA and Knight, R}, title = {The Oral and Skin Microbiomes of Captive Komodo Dragons Are Significantly Shared with Their Habitat.}, journal = {mSystems}, volume = {1}, number = {4}, pages = {}, pmid = {27822543}, issn = {2379-5077}, support = {T32 EB009412/EB/NIBIB NIH HHS/United States ; }, abstract = {Examining the way in which animals, including those in captivity, interact with their environment is extremely important for studying ecological processes and developing sophisticated animal husbandry. Here we use the Komodo dragon (Varanus komodoensis) to quantify the degree of sharing of salivary, skin, and fecal microbiota with their environment in captivity. Both species richness and microbial community composition of most surfaces in the Komodo dragon's environment are similar to the Komodo dragon's salivary and skin microbiota but less similar to the stool-associated microbiota. We additionally compared host-environment microbiome sharing between captive Komodo dragons and their enclosures, humans and pets and their homes, and wild amphibians and their environments. We observed similar host-environment microbiome sharing patterns among humans and their pets and Komodo dragons, with high levels of human/pet- and Komodo dragon-associated microbes on home and enclosure surfaces. In contrast, only small amounts of amphibian-associated microbes were detected in the animals' environments. We suggest that the degree of sharing between the Komodo dragon microbiota and its enclosure surfaces has important implications for animal health. These animals evolved in the context of constant exposure to a complex environmental microbiota, which likely shaped their physiological development; in captivity, these animals will not receive significant exposure to microbes not already in their enclosure, with unknown consequences for their health. IMPORTANCE Animals, including humans, have evolved in the context of exposure to a variety of microbial organisms present in the environment. Only recently have humans, and some animals, begun to spend a significant amount of time in enclosed artificial environments, rather than in the more natural spaces in which most of evolution took place. The consequences of this radical change in lifestyle likely extend to the microbes residing in and on our bodies and may have important implications for health and disease. A full characterization of host-microbe sharing in both closed and open environments will provide crucial information that may enable the improvement of health in humans and in captive animals, both of which experience a greater incidence of disease (including chronic illness) than counterparts living under more ecologically natural conditions.}, }
@article {pmid27819657, year = {2016}, author = {Lagier, JC and Khelaifia, S and Alou, MT and Ndongo, S and Dione, N and Hugon, P and Caputo, A and Cadoret, F and Traore, SI and Seck, EH and Dubourg, G and Durand, G and Mourembou, G and Guilhot, E and Togo, A and Bellali, S and Bachar, D and Cassir, N and Bittar, F and Delerce, J and Mailhe, M and Ricaboni, D and Bilen, M and Dangui Nieko, NP and Dia Badiane, NM and Valles, C and Mouelhi, D and Diop, K and Million, M and Musso, D and Abrahão, J and Azhar, EI and Bibi, F and Yasir, M and Diallo, A and Sokhna, C and Djossou, F and Vitton, V and Robert, C and Rolain, JM and La Scola, B and Fournier, PE and Levasseur, A and Raoult, D}, title = {Culture of previously uncultured members of the human gut microbiota by culturomics.}, journal = {Nature microbiology}, volume = {1}, number = {}, pages = {16203}, doi = {10.1038/nmicrobiol.2016.203}, pmid = {27819657}, issn = {2058-5276}, mesh = {Archaea/classification/genetics/*growth &amp; development/*isolation &amp; purification ; Bacteria/classification/genetics/*growth &amp; development/*isolation &amp; purification ; DNA, Archaeal/chemistry/genetics ; DNA, Bacterial/chemistry/genetics ; DNA, Ribosomal/chemistry/genetics ; Gastrointestinal Microbiome ; Gastrointestinal Tract/*microbiology ; Humans ; Microbiological Techniques/*methods ; Microbiota ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA/methods ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization/methods ; }, abstract = {Metagenomics revolutionized the understanding of the relations among the human microbiome, health and diseases, but generated a countless number of sequences that have not been assigned to a known microorganism[1]. The pure culture of prokaryotes, neglected in recent decades, remains essential to elucidating the role of these organisms[2]. We recently introduced microbial culturomics, a culturing approach that uses multiple culture conditions and matrix-assisted laser desorption/ionization-time of flight and 16S rRNA for identification[2]. Here, we have selected the best culture conditions to increase the number of studied samples and have applied new protocols (fresh-sample inoculation; detection of microcolonies and specific cultures of Proteobacteria and microaerophilic and halophilic prokaryotes) to address the weaknesses of the previous studies[3-5]. We identified 1,057 prokaryotic species, thereby adding 531 species to the human gut repertoire: 146 bacteria known in humans but not in the gut, 187 bacteria and 1 archaea not previously isolated in humans, and 197 potentially new species. Genome sequencing was performed on the new species. By comparing the results of the metagenomic and culturomic analyses, we show that the use of culturomics allows the culture of organisms corresponding to sequences previously not assigned. Altogether, culturomics doubles the number of species isolated at least once from the human gut.}, }
@article {pmid27807746, year = {2016}, author = {Han, M and Yang, P and Zhou, H and Li, H and Ning, K}, title = {Metagenomics and Single-Cell Omics Data Analysis for Human Microbiome Research.}, journal = {Advances in experimental medicine and biology}, volume = {939}, number = {}, pages = {117-137}, doi = {10.1007/978-981-10-1503-8_6}, pmid = {27807746}, issn = {0065-2598}, mesh = {DNA Barcoding, Taxonomic/*methods ; Genotype ; High-Throughput Nucleotide Sequencing ; Humans ; *Metagenome ; Metagenomics/*methods ; Microbiota/*genetics ; Phenotype ; Polymorphism, Single Nucleotide ; Single-Cell Analysis/*methods ; }, abstract = {Microbes are ubiquitous on our planet, and it is well known that the total number of microbial cells on earth is huge. These organisms usually live in communities, and each of these communities has a different taxonomical structure. As such, microbial communities would serve as the largest reservoir of genes and genetic functions for a vast number of applications in "bio"-related disciplines, especially in biomedicine. Human microbiome is the area in which the relationships between ourselves as hosts and our microbiomes have been examined.In this chapter, we have first reviewed the researches in microbes on community, population and single-cell levels in general. Then we have focused on the effects of recent metagenomics and single-cell advances on human microbiome research, as well as their effects on translational biomedical research. We have also foreseen that with the advancement of big-data analysis techniques, deeper understanding of human microbiome, as well as its broader applications, could be realized.}, }
@article {pmid27806346, year = {2017}, author = {Botticelli, A and Zizzari, I and Mazzuca, F and Ascierto, PA and Putignani, L and Marchetti, L and Napoletano, C and Nuti, M and Marchetti, P}, title = {Cross-talk between microbiota and immune fitness to steer and control response to anti PD-1/PDL-1 treatment.}, journal = {Oncotarget}, volume = {8}, number = {5}, pages = {8890-8899}, pmid = {27806346}, issn = {1949-2553}, mesh = {Animals ; Antineoplastic Agents, Immunological/*therapeutic use ; B7-H1 Antigen/*antagonists &amp; inhibitors/immunology/metabolism ; Gastrointestinal Microbiome/*immunology ; Gastrointestinal Tract/*microbiology ; Host-Pathogen Interactions ; Humans ; Neoplasms/*drug therapy/immunology/metabolism/microbiology ; Programmed Cell Death 1 Receptor/antagonists &amp; inhibitors/immunology/metabolism ; Signal Transduction/drug effects ; Treatment Outcome ; }, abstract = {Immune Checkpoint Inhibitors (ICIs) are improving the survival of cancer patients, however only the 20-30% of treated patients present clinical benefits. Toxicity represents the major cause of reduced dosage, delayed drug administration and therapy discontinuation. Hence in the context of multiple treatment possibilities, the identification of predictive markers of response and toxicity is a challenging approach for drug selection in order to obtain the best clinical benefit while minimizing the side effects. The loss of the protective function of intestinal barriers that interacts with the environment measured as increased intestinal permeability and the changes occurring in the microbiota composition have been proposed as a mechanism potentially explaining the pathogenesis of immune related toxicity.In this review we discuss the new perspectives on the involvement of PD-1 and PDL-1 in the cross talk between gut microbiota and immune fitness and how gut microbiota impacts on the efficacy of anti-PD-1 and anti-PDL-1 treatments in cancer.}, }
@article {pmid27803195, year = {2016}, author = {Nayfach, S and Rodriguez-Mueller, B and Garud, N and Pollard, KS}, title = {An integrated metagenomics pipeline for strain profiling reveals novel patterns of bacterial transmission and biogeography.}, journal = {Genome research}, volume = {26}, number = {11}, pages = {1612-1625}, pmid = {27803195}, issn = {1549-5469}, support = {T32 GM067547/GM/NIGMS NIH HHS/United States ; }, mesh = {Adult ; Bacteria/classification/genetics ; Bacterial Infections/transmission ; DNA Fingerprinting/*methods/standards ; Feces/microbiology ; Female ; *Genome, Bacterial ; Humans ; Infant ; *Infectious Disease Transmission, Vertical ; *Metagenome ; Metagenomics/*methods/standards ; Phylogeny ; Phylogeography ; Polymorphism, Single Nucleotide ; Reference Standards ; Sequence Analysis, DNA/methods/standards ; Soil Microbiology ; Water Microbiology ; }, abstract = {We present the Metagenomic Intra-species Diversity Analysis System (MIDAS), which is an integrated computational pipeline for quantifying bacterial species abundance and strain-level genomic variation, including gene content and single-nucleotide polymorphisms (SNPs), from shotgun metagenomes. Our method leverages a database of more than 30,000 bacterial reference genomes that we clustered into species groups. These cover the majority of abundant species in the human microbiome but only a small proportion of microbes in other environments, including soil and seawater. We applied MIDAS to stool metagenomes from 98 Swedish mothers and their infants over one year and used rare SNPs to track strains between hosts. Using this approach, we found that although species compositions of mothers and infants converged over time, strain-level similarity diverged. Specifically, early colonizing bacteria were often transmitted from an infant's mother, while late colonizing bacteria were often transmitted from other sources in the environment and were enriched for spore-formation genes. We also applied MIDAS to 198 globally distributed marine metagenomes and used gene content to show that many prevalent bacterial species have population structure that correlates with geographic location. Strain-level genetic variants present in metagenomes clearly reveal extensive structure and dynamics that are obscured when data are analyzed at a coarser taxonomic resolution.}, }
@article {pmid27676197, year = {2016}, author = {Koopen, AM and Groen, AK and Nieuwdorp, M}, title = {Human microbiome as therapeutic intervention target to reduce cardiovascular disease risk.}, journal = {Current opinion in lipidology}, volume = {27}, number = {6}, pages = {615-622}, doi = {10.1097/MOL.0000000000000357}, pmid = {27676197}, issn = {1473-6535}, mesh = {Cardiovascular Diseases/*drug therapy/metabolism/*microbiology ; Gastrointestinal Microbiome/drug effects ; Humans ; Microbiota/*drug effects ; Molecular Targeted Therapy/*methods ; Myocardium/metabolism ; Risk ; }, abstract = {PURPOSE OF REVIEW: The absolute burden of cardiovascular risk remains high despite currently available preventive and therapeutic options. In search for novel therapeutic leads, mounting evidence has linked the gut microbiota as well as their metabolites to the development of cardiometabolic diseases.<br><br>RECENT FINDINGS: The intestinal microbiota influences the host via different metabolic pathways as inducer of endotoxemia, formation of trimethylamine-N-oxide, production of short chain fatty acids, and is a regulator in intestinal bile acid metabolism. Disruption of the gut microbiome may disturb the homeostasis of the microbial ecosystem to an alternative stable state associated with pathophysiological traits in microbiota and host. However, causality has not been shown yet.<br><br>SUMMARY: We are just beginning to understand how the gut microbiota influence our cardiometabolic health and various innovative therapeutic options are in the developing (preclinical) phase. This review focuses on the current evidence whether and to what extent the intestinal microbiota are involved in cardiovascular disease and whether this is based on merely association or causal relations.}, }
@article {pmid27742762, year = {2018}, author = {Fan, X and Alekseyenko, AV and Wu, J and Peters, BA and Jacobs, EJ and Gapstur, SM and Purdue, MP and Abnet, CC and Stolzenberg-Solomon, R and Miller, G and Ravel, J and Hayes, RB and Ahn, J}, title = {Human oral microbiome and prospective risk for pancreatic cancer: a population-based nested case-control study.}, journal = {Gut}, volume = {67}, number = {1}, pages = {120-127}, pmid = {27742762}, issn = {1468-3288}, support = {R01 CA159036/CA/NCI NIH HHS/United States ; P30 CA016087/CA/NCI NIH HHS/United States ; P30 ES000260/ES/NIEHS NIH HHS/United States ; R21 CA183887/CA/NCI NIH HHS/United States ; R03 CA159414/CA/NCI NIH HHS/United States ; U01 CA182370/CA/NCI NIH HHS/United States ; R01 CA164964/CA/NCI NIH HHS/United States ; }, mesh = {Adenocarcinoma/*microbiology ; Aged ; Aggregatibacter actinomycetemcomitans/isolation &amp; purification ; Carrier State/microbiology ; Case-Control Studies ; Female ; Fusobacteria/isolation &amp; purification ; High-Throughput Nucleotide Sequencing/methods ; Humans ; Male ; *Microbiota ; Middle Aged ; Mouth/*microbiology ; Pancreatic Neoplasms/*microbiology ; Periodontium/microbiology ; Porphyromonas gingivalis/isolation &amp; purification ; Prospective Studies ; Risk Factors ; }, abstract = {OBJECTIVE: A history of periodontal disease and the presence of circulating antibodies to selected oral pathogens have been associated with increased risk of pancreatic cancer; however, direct relationships of oral microbes with pancreatic cancer have not been evaluated in prospective studies. We examine the relationship of oral microbiota with subsequent risk of pancreatic cancer in a large nested case-control study.<br><br>DESIGN: We selected 361 incident adenocarcinoma of pancreas and 371 matched controls from two prospective cohort studies, the American Cancer Society Cancer Prevention Study II and the National Cancer Institute Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. From pre-diagnostic oral wash samples, we characterised the composition of the oral microbiota using bacterial 16S ribosomal RNA (16S rRNA) gene sequencing. The associations between oral microbiota and risk of pancreatic cancer, controlling for the random effect of cohorts and other covariates, were examined using traditional and L1-penalised least absolute shrinkage and selection operator logistic regression.<br><br>RESULTS: Carriage of oral pathogens, Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans, were associated with higher risk of pancreatic cancer (adjusted OR for presence vs absence=1.60 and 95% CI 1.15 to 2.22; OR=2.20 and 95% CI 1.16 to 4.18, respectively). Phylum Fusobacteria and its genus Leptotrichia were associated with decreased pancreatic cancer risk (OR per per cent increase of relative abundance=0.94 and 95% CI 0.89 to 0.99; OR=0.87 and 95% CI 0.79 to 0.95, respectively). Risks related to these phylotypes remained after exclusion of cases that developed within 2&#x2005;years of sample collection, reducing the likelihood of reverse causation in this prospective study.<br><br>CONCLUSIONS: This study provides supportive evidence that oral microbiota may play a role in the aetiology of pancreatic cancer.}, }
@article {pmid27795334, year = {2017}, author = {Munson, E and Carroll, KC}, title = {What's in a Name? New Bacterial Species and Changes to Taxonomic Status from 2012 through 2015.}, journal = {Journal of clinical microbiology}, volume = {55}, number = {1}, pages = {24-42}, pmid = {27795334}, issn = {1098-660X}, mesh = {Bacteria/*classification/*isolation &amp; purification ; Bacterial Infections/*microbiology ; Classification/*methods ; Humans ; *Terminology as Topic ; }, abstract = {Technological advancements in fields such as molecular genetics and the human microbiome have resulted in an unprecedented recognition of new bacterial genus/species designations by the International Journal of Systematic and Evolutionary Microbiology Knowledge of designations involving clinically significant bacterial species would benefit clinical microbiologists in the context of emerging pathogens, performance of accurate organism identification, and antimicrobial susceptibility testing. In anticipation of subsequent taxonomic changes being compiled by the Journal of Clinical Microbiology on a biannual basis, this compendium summarizes novel species and taxonomic revisions specific to bacteria derived from human clinical specimens from the calendar years 2012 through 2015.}, }
@article {pmid27769987, year = {2016}, author = {Yamamura, K and Baba, Y and Nakagawa, S and Mima, K and Miyake, K and Nakamura, K and Sawayama, H and Kinoshita, K and Ishimoto, T and Iwatsuki, M and Sakamoto, Y and Yamashita, Y and Yoshida, N and Watanabe, M and Baba, H}, title = {Human Microbiome Fusobacterium Nucleatum in Esophageal Cancer Tissue Is Associated with Prognosis.}, journal = {Clinical cancer research : an official journal of the American Association for Cancer Research}, volume = {22}, number = {22}, pages = {5574-5581}, doi = {10.1158/1078-0432.CCR-16-1786}, pmid = {27769987}, issn = {1557-3265}, mesh = {Aged ; Chemokines/metabolism ; DNA, Bacterial/genetics ; Esophageal Neoplasms/metabolism/*microbiology/*pathology ; Female ; Fusobacterium nucleatum/*genetics ; Humans ; Male ; Microbiota/*genetics ; Prognosis ; }, abstract = {PURPOSE: Fusobacterium nucleatum (F. nucleatum) is a component of the human microbiome that primarily inhabits the oral cavity. It causes periodontal disease and has also been implicated in the development of human cancers. Although there are several reports of the relationship between F. nucleatum and the clinical outcome in human cancers, its prognostic significance in esophageal cancer remains unclear.<br><br>EXPERIMENTAL DESIGN: We quantified F. nucleatum DNA in 325 resected esophageal cancer specimens by qPCR. Significant pathways in F. nucleatum-positive esophageal cancer tissues were identified by Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis using microarray data.<br><br>RESULTS: Esophageal cancer tissues contained significantly more F. nucleatum DNA than matched normal esophageal mucosa (P = 0.021; n = 60). F. nucleatum DNA was detected in 74 of 325 cases (23%). F. nucleatum DNA positivity was significantly associated with tumor stage, but not with sex, age, performance status, tobacco use, alcohol use, histology, tumor location, or preoperative treatment. F. nucleatum DNA positivity was also significantly associated with cancer-specific survival [log-rank P = 0.0039; univariate HR = 2.01; 95% confidence interval (CI), 1.22-3.23; P = 0.0068; multivariate HR = 1.78; 95% CI, 1.06-2.94; P = 0.031]. The top-ranked KEGG pathway in F. nucleatum-positive tissues was "cytokine-cytokine receptor interaction." A significant relationship between F. nucleatum and the chemokine CCL20 was validated by IHC.<br><br>CONCLUSIONS: F. nucleatum in esophageal cancer tissues was associated with shorter survival, suggesting a potential role as a prognostic biomarker. F. nucleatum might also contribute to aggressive tumor behavior through activation of chemokines, such as CCL20. Clin Cancer Res; 22(22); 5574-81. &#xa9;2016 AACR.}, }
@article {pmid27622700, year = {2016}, author = {Albenberg, L and Kelsen, J}, title = {Advances in Gut Microbiome Research and Relevance to Pediatric Diseases.}, journal = {The Journal of pediatrics}, volume = {178}, number = {}, pages = {16-23}, doi = {10.1016/j.jpeds.2016.08.044}, pmid = {27622700}, issn = {1097-6833}, mesh = {Biomedical Research ; Child ; Child, Preschool ; *Gastrointestinal Microbiome ; Humans ; Infant ; Pediatrics ; }, }
@article {pmid27785127, year = {2016}, author = {Abdul-Aziz, MA and Cooper, A and Weyrich, LS}, title = {Exploring Relationships between Host Genome and Microbiome: New Insights from Genome-Wide Association Studies.}, journal = {Frontiers in microbiology}, volume = {7}, number = {}, pages = {1611}, pmid = {27785127}, issn = {1664-302X}, abstract = {As our understanding of the human microbiome expands, impacts on health and disease continue to be revealed. Alterations in the microbiome can result in dysbiosis, which has now been linked to subsequent autoimmune and metabolic diseases, highlighting the need to identify factors that shape the microbiome. Research has identified that the composition and functions of the human microbiome can be influenced by diet, age, sex, and environment. More recently, studies have explored how human genetic variation may also influence the microbiome. Here, we review several recent analytical advances in this new research area, including those that use genome-wide association studies to examine host genome-microbiome interactions, while controlling for the influence of other factors. We find that current research is limited by small sample sizes, lack of cohort replication, and insufficient confirmatory mechanistic studies. In addition, we discuss the importance of understanding long-term interactions between the host genome and microbiome, as well as the potential impacts of disrupting this relationship, and explore new research avenues that may provide information about the co-evolutionary history of humans and their microorganisms.}, }
@article {pmid27663468, year = {2016}, author = {Del Chierico, F and Di Cave, D and Accardi, C and Santoro, M and Masotti, A and D'Alfonso, R and Berrilli, F and Urbani, A and Putignani, L}, title = {Identification and typing of free-living Acanthamoeba spp. by MALDI-TOF MS Biotyper.}, journal = {Experimental parasitology}, volume = {170}, number = {}, pages = {82-89}, doi = {10.1016/j.exppara.2016.09.007}, pmid = {27663468}, issn = {1090-2449}, mesh = {Acanthamoeba/*classification/genetics/growth &amp; development/*isolation &amp; purification ; Acanthamoeba Keratitis/*parasitology ; Cluster Analysis ; DNA, Protozoan/chemistry/isolation &amp; purification ; DNA, Ribosomal/genetics ; Genotype ; Genotyping Techniques/methods/standards ; Humans ; Phenotype ; Phylogeny ; Polymerase Chain Reaction ; Proteomics/methods ; RNA, Ribosomal, 18S/genetics ; Reproducibility of Results ; *Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization ; }, abstract = {Over the years, the potential pathogenicity of Acanthamoeba for humans and animals has gained increasing attention from the scientific community. More than 24 species belong to this genus, however only some of them are causative agents of keratitis and encephalitis in humans. Due to technical difficulties in diagnosis, these infections are likely to be under-detected. The introduction of 18S rDNA amplification for the identification of Acanthamoeba has dramatically enhanced diagnosis performances, but the attestation of genotyping requires supplementary sequencing-based procedures. In this study, 15 Acanthamoeba strains were collected and grown on nutrient agar media. Each strain was genotyped by end-point PCR assay for the amplification of the 18S rDNA gene and the genotype was assigned by sequencing analysis through neighbor joining phylogenetic tree. In order to optimize standardization of the MALDI-TOF MS assay, we established the collection time point at the cystic phase. Two strains of each genotype were randomly chosen to customize the biotyper database. For all strains, 24 spectral measurements were acquired and submitted to identification and cluster analysis of spectra. The obtained results highlighted the correct identification of Acanthamoeba strains and the overlapping of spectra dendrogram clusters to the 18S genotype assignations. In conclusion, the MALDI-TOF MS Biotyper revealed the capability to identify and genotype the Acanthamoeba strains, providing a new frontier in the diagnostic identification of amaebae and in taxonomic and phylogenetic studies.}, }
@article {pmid27782139, year = {2016}, author = {Livanos, AE and Greiner, TU and Vangay, P and Pathmasiri, W and Stewart, D and McRitchie, S and Li, H and Chung, J and Sohn, J and Kim, S and Gao, Z and Barber, C and Kim, J and Ng, S and Rogers, AB and Sumner, S and Zhang, XS and Cadwell, K and Knights, D and Alekseyenko, A and Bäckhed, F and Blaser, MJ}, title = {Antibiotic-mediated gut microbiome perturbation accelerates development of type 1 diabetes in mice.}, journal = {Nature microbiology}, volume = {1}, number = {11}, pages = {16140}, pmid = {27782139}, issn = {2058-5276}, support = {P30 CA016087/CA/NCI NIH HHS/United States ; T32 GM007308/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Anti-Bacterial Agents/administration &amp; dosage/*adverse effects ; Cholesterol/biosynthesis ; Diabetes Mellitus, Type 1/*etiology ; Drug Administration Schedule ; Feces/microbiology ; Gastrointestinal Microbiome/*drug effects/genetics/physiology ; Gene Expression/drug effects ; Genetic Predisposition to Disease ; Lipid Metabolism/drug effects ; Metabolome/drug effects ; Mice ; Mice, Inbred NOD ; Mucous Membrane/drug effects/immunology ; Obesity ; Penicillin V/administration &amp; dosage/*adverse effects ; RNA, Ribosomal, 16S ; T-Lymphocytes, Regulatory ; Th17 Cells ; }, abstract = {The early life microbiome plays important roles in host immunological and metabolic development. Because the incidence of type 1 diabetes (T1D) has been increasing substantially in recent decades, we hypothesized that early-life antibiotic use alters gut microbiota, which predisposes to disease. Using non-obese diabetic mice that are genetically susceptible to T1D, we examined the effects of exposure to either continuous low-dose antibiotics or pulsed therapeutic antibiotics (PAT) early in life, mimicking childhood exposures. We found that in mice receiving PAT, T1D incidence was significantly higher, and microbial community composition and structure differed compared with controls. In pre-diabetic male PAT mice, the intestinal lamina propria had lower Th17 and Treg proportions and intestinal SAA expression than in controls, suggesting key roles in transducing the altered microbiota signals. PAT affected microbial lipid metabolism and host cholesterol biosynthetic gene expression. These findings show that early-life antibiotic treatments alter the gut microbiota and its metabolic capacities, intestinal gene expression and T-cell populations, accelerating T1D onset in non-obese diabetic mice.}, }
@article {pmid27781166, year = {2016}, author = {Joseph, SJ and Li, B and Petit Iii, RA and Qin, ZS and Darrow, L and Read, TD}, title = {The single-species metagenome: subtyping Staphylococcus aureus core genome sequences from shotgun metagenomic data.}, journal = {PeerJ}, volume = {4}, number = {}, pages = {e2571}, pmid = {27781166}, issn = {2167-8359}, support = {R21 AI121860/AI/NIAID NIH HHS/United States ; }, abstract = {In this study we developed a genome-based method for detecting Staphylococcus aureus subtypes from metagenome shotgun sequence data. We used a binomial mixture model and the coverage counts at >100,000 known S. aureus SNP (single nucleotide polymorphism) sites derived from prior comparative genomic analysis to estimate the proportion of 40 subtypes in metagenome samples. We were able to obtain >87% sensitivity and >94% specificity at 0.025X coverage for S. aureus. We found that 321 and 149 metagenome samples from the Human Microbiome Project and metaSUB analysis of the New York City subway, respectively, contained S. aureus at genome coverage >0.025. In both projects, CC8 and CC30 were the most common S. aureus clonal complexes encountered. We found evidence that the subtype composition at different body sites of the same individual were more similar than random sampling and more limited evidence that certain body sites were enriched for particular subtypes. One surprising finding was the apparent high frequency of CC398, a lineage often associated with livestock, in samples from the tongue dorsum. Epidemiologic analysis of the HMP subject population suggested that high BMI (body mass index) and health insurance are possibly associated with S. aureus carriage but there was limited power to identify factors linked to carriage of even the most common subtype. In the NYC subway data, we found a small signal of geographic distance affecting subtype clustering but other unknown factors influence taxonomic distribution of the species around the city.}, }
@article {pmid27748750, year = {2016}, author = {Chu, J and Vila-Farres, X and Inoyama, D and Ternei, M and Cohen, LJ and Gordon, EA and Reddy, BV and Charlop-Powers, Z and Zebroski, HA and Gallardo-Macias, R and Jaskowski, M and Satish, S and Park, S and Perlin, DS and Freundlich, JS and Brady, SF}, title = {Discovery of MRSA active antibiotics using primary sequence from the human microbiome.}, journal = {Nature chemical biology}, volume = {12}, number = {12}, pages = {1004-1006}, pmid = {27748750}, issn = {1552-4469}, support = {F32 AI110029/AI/NIAID NIH HHS/United States ; T32 DK007792/DK/NIDDK NIH HHS/United States ; U19 AI109713/AI/NIAID NIH HHS/United States ; }, mesh = {Anti-Bacterial Agents/chemical synthesis/chemistry/*isolation &amp; purification/*pharmacology ; Biological Products/chemical synthesis/chemistry/*isolation &amp; purification/*pharmacology ; Drug Discovery/*methods ; Humans ; Lipopeptides/chemical synthesis/chemistry/genetics/pharmacology ; Methicillin-Resistant Staphylococcus aureus/*drug effects/enzymology ; Microbial Sensitivity Tests ; Microbiota/*genetics ; Molecular Conformation ; Peptide Synthases/genetics ; beta-Lactams/agonists/metabolism ; }, abstract = {Here we present a natural product discovery approach, whereby structures are bioinformatically predicted from primary sequence and produced by chemical synthesis (synthetic-bioinformatic natural products, syn-BNPs), circumventing the need for bacterial culture and gene expression. When we applied the approach to nonribosomal peptide synthetase gene clusters from human-associated bacteria, we identified the humimycins. These antibiotics inhibit lipid II flippase and potentiate β-lactam activity against methicillin-resistant Staphylococcus aureus in mice, potentially providing a new treatment regimen.}, }
@article {pmid27770008, year = {2017}, author = {Yu, G and Phillips, S and Gail, MH and Goedert, JJ and Humphrys, M and Ravel, J and Ren, Y and Caporaso, NE}, title = {Evaluation of Buccal Cell Samples for Studies of Oral Microbiota.}, journal = {Cancer epidemiology, biomarkers &amp; prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology}, volume = {26}, number = {2}, pages = {249-253}, doi = {10.1158/1055-9965.EPI-16-0538}, pmid = {27770008}, issn = {1538-7755}, mesh = {Adult ; Aged ; Feasibility Studies ; Female ; Follow-Up Studies ; Healthy Volunteers ; Humans ; Male ; Microbiota/*genetics ; Middle Aged ; Mouth Diseases/diagnosis/genetics/microbiology ; Mouth Mucosa/cytology/*microbiology ; Prospective Studies ; RNA, Bacterial/*analysis ; RNA, Ribosomal, 16S/analysis/*genetics ; }, abstract = {BACKGROUND: The human microbiota is postulated to affect cancer risk, but collecting microbiota specimens with prospective follow-up for diseases will take time. Buccal cell samples have been obtained from mouthwash for the study of human genomic DNA in many cohort studies. Here, we evaluate the feasibility of using buccal cell samples to examine associations of human microbiota and disease risk.<br><br>METHODS: We obtained buccal cells from mouthwash in 41 healthy participants using a protocol that is widely employed to obtain buccal cells for the study of human DNA. We compared oral microbiota from buccal cells with that from eight other oral sample types collected by following the protocols of the Human Microbiome Project. Microbiota profiles were determined by sequencing 16S rRNA gene V3-V4 region.<br><br>RESULTS: Compared with each of the eight other oral samples, the buccal cell samples had significantly more observed species (P < 0.002) and higher alpha diversity (Shannon index, P < 0.02). The microbial communities were more similar (smaller beta diversity) among buccal cells samples than in the other samples (P < 0.001 for 12 of 16 weighted and unweighted UniFrac distance comparisons). Buccal cell microbial profiles closely resembled saliva but were distinct from dental plaque and tongue dorsum.<br><br>CONCLUSIONS: Stored buccal cell samples in prospective cohort studies are a promising resource to study associations of oral microbiota with disease.<br><br>IMPACT: The feasibility of using existing buccal cell collections in large prospective cohorts allows investigations of the role of oral microbiota in chronic disease etiology in large population studies possible today. Cancer Epidemiol Biomarkers Prev; 26(2); 249-53. &#xa9;2016 AACR.}, }
@article {pmid27767329, year = {2017}, author = {Daliri, EB and Wei, S and Oh, DH and Lee, BH}, title = {The human microbiome and metabolomics: Current concepts and applications.}, journal = {Critical reviews in food science and nutrition}, volume = {57}, number = {16}, pages = {3565-3576}, doi = {10.1080/10408398.2016.1220913}, pmid = {27767329}, issn = {1549-7852}, mesh = {Animals ; Dysbiosis ; Gastrointestinal Tract/*microbiology ; Humans ; Intestines ; *Metabolomics ; Microbiota ; }, abstract = {The mammalian gastrointestinal tract has co-developed with a large number of microbes in a symbiotic relationship over millions of years. Recent studies indicate that indigenous bacteria are intimate with the intestine and play essential roles in health and disease. In the quest to maintain a stable niche, these prokaryotes influence multiple host metabolic pathways, resulting from an interactive host-microbiota metabolic signaling and impacting strongly on the metabolic phenotypes of the host. Since dysbiosis of the gut bacteria result in alteration in the levels of certain microbial and host co-metabolites, identifying these markers could enhance early detection of diseases. Also, identification of these metabolic fingerprints could give us clues as to how to manipulate the microbiome to promote health or treat diseases. This review provides an overview of our current knowledge of the microbiome and metablomics, applications and the future perspectives.}, }
@article {pmid27766372, year = {2017}, author = {Willmann, M and Peter, S}, title = {Translational metagenomics and the human resistome: confronting the menace of the new millennium.}, journal = {Journal of molecular medicine (Berlin, Germany)}, volume = {95}, number = {1}, pages = {41-51}, pmid = {27766372}, issn = {1432-1440}, mesh = {Anti-Bacterial Agents/pharmacology/therapeutic use ; Bacterial Infections/diagnosis/drug therapy/microbiology ; *Drug Resistance, Microbial ; Humans ; Infection Control ; *Metagenome ; *Metagenomics/methods ; Microbiota/*drug effects/*genetics ; Translational Research, Biomedical ; }, abstract = {The increasing threat of antimicrobial resistance poses one of the greatest challenges to modern medicine. The collection of all antimicrobial resistance genes carried by various microorganisms in the human body is called the human resistome and represents the source of resistance in pathogens that can eventually cause life-threatening and untreatable infections. A deep understanding of the human resistome and its multilateral interaction with various environments is necessary for developing proper measures that can efficiently reduce the spread of resistance. However, the human resistome and its evolution still remain, for the most part, a mystery to researchers. Metagenomics, particularly in combination with next-generation-sequencing technology, provides a powerful methodological approach for studying the human microbiome as well as the pathogenome, the virolume and especially the resistome. We summarize below current knowledge on how the human resistome is shaped and discuss how metagenomics can be employed to improve our understanding of these complex processes, particularly as regards a rapid translation of new findings into clinical diagnostics, infection control and public health.}, }
@article {pmid27761936, year = {2017}, author = {Moos, WH and Pinkert, CA and Irwin, MH and Faller, DV and Kodukula, K and Glavas, IP and Steliou, K}, title = {Epigenetic Treatment of Persistent Viral Infections.}, journal = {Drug development research}, volume = {78}, number = {1}, pages = {24-36}, doi = {10.1002/ddr.21366}, pmid = {27761936}, issn = {1098-2299}, mesh = {Anti-Infective Agents/pharmacology/*therapeutic use ; Epigenesis, Genetic/drug effects ; Gene Editing ; Humans ; Immunity ; Microbiota ; Small Molecule Libraries/*pharmacology/therapeutic use ; Synthetic Biology ; Virus Diseases/*drug therapy/genetics/immunology ; Viruses/drug effects/*genetics ; }, abstract = {Preclinical Research Approximately 2,500 years ago, Hippocrates used the word herpes as a medical term to describe lesions that appeared to creep or crawl on the skin, advocating heat as a possible treatment. During the last 50 years, pharmaceutical research has made great strides, and therapeutic options have expanded to include small molecule antiviral agents, protease inhibitors, preventive vaccines for a handful of the papillomaviruses, and even cures for hepatitis C virus infections. However, effective treatments for persistent and recurrent viral infections, particularly the highly prevalent herpesviruses, continue to represent a significant unmet medical need, affecting the majority of the world's population. Exploring the population diversity of the human microbiome and the effects its compositional variances have on the immune system, health, and disease are the subjects of intense investigational research and study. Among the collection of viruses, bacteria, fungi, and single-cell eukaryotes that comprise the human microbiome, the virome has been grossly understudied relative to the influence it exerts on human pathophysiology, much as mitochondria have until recently failed to receive the attention they deserve, given their critical biomedical importance. Fortunately, cellular epigenetic machinery offers a wealth of druggable targets for therapeutic intervention in numerous disease indications, including those outlined above. With advances in synthetic biology, engineering our body's commensal microorganisms to seek out and destroy pathogenic species is clearly on the horizon. This is especially the case given recent breakthroughs in genetic manipulation with tools such as the CRISPR/Cas (clustered regularly interspaced short palindromic repeats/CRISPR-associated) gene-editing platforms. Tying these concepts together with our previous work on the microbiome and neurodegenerative and neuropsychiatric diseases, we suggest that, because mammalian cells respond to a viral infection by triggering a cascade of antiviral innate immune responses governed substantially by the cell's mitochondria, small molecule carnitinoids represent a new class of therapeutics with potential widespread utility against many infectious insults. Drug Dev Res 78 : 24-36, 2017. © 2016 Wiley Periodicals, Inc.}, }
@article {pmid27760679, year = {2016}, author = {Diop, A and Khelaifia, S and Armstrong, N and Labas, N and Fournier, PE and Raoult, D and Million, M}, title = {Microbial culturomics unravels the halophilic microbiota repertoire of table salt: description of Gracilibacillus massiliensis sp. nov.}, journal = {Microbial ecology in health and disease}, volume = {27}, number = {}, pages = {32049}, pmid = {27760679}, issn = {0891-060X}, abstract = {BACKGROUND: Microbial culturomics represents an ongoing revolution in the characterization of environmental and human microbiome.<br><br>METHODS: By using three media containing high salt concentration (100, 150, and 200 g/L), the halophilic microbial culturome of a commercial table salt was determined.<br><br>RESULTS: Eighteen species belonging to the Terrabacteria group were isolated including eight moderate halophilic and 10 halotolerant bacteria. Gracilibacillus massiliensis sp. nov., type strain Awa-1[T] (=CSUR P1441=DSM 29726), is a moderately halophilic gram-positive, non-spore-forming rod, and is motile by using a flagellum. Strain Awa-1[T] shows catalase activity but no oxidase activity. It is not only an aerobic bacterium but also able to grow in anaerobic and microaerophilic atmospheres. The draft genome of G. massiliensis is 4,207,226 bp long, composed of 13 scaffolds with 36.05% of G+C content. It contains 3,908 genes (3,839 protein-coding and 69 RNA genes). At least 1,983 (52%) orthologous proteins were not shared with the closest phylogenetic species. Hundred twenty-six genes (3.3%) were identified as ORFans.<br><br>CONCLUSIONS: Microbial culturomics can dramatically improve the characterization of the food and environmental microbiota repertoire, deciphering new bacterial species and new genes. Further studies will clarify the geographic specificity and the putative role of these new microbes and their related functional genetic content in environment, health, and disease.}, }
@article {pmid27713999, year = {2016}, author = {Li, R and Li, F and Feng, Q and Liu, Z and Jie, Z and Wen, B and Xu, X and Zhong, S and Li, G and He, K}, title = {An LC-MS based untargeted metabolomics study identified novel biomarkers for coronary heart disease.}, journal = {Molecular bioSystems}, volume = {12}, number = {11}, pages = {3425-3434}, doi = {10.1039/c6mb00339g}, pmid = {27713999}, issn = {1742-2051}, mesh = {Adult ; Aged ; Biomarkers ; Case-Control Studies ; Chromatography, Liquid ; Cluster Analysis ; Coronary Artery Disease/*metabolism/pathology ; Disease Progression ; Energy Metabolism ; Female ; Humans ; Male ; Mass Spectrometry ; *Metabolome ; *Metabolomics/methods ; Middle Aged ; ROC Curve ; }, abstract = {This study performed untargeted metabolomics for plasma samples from 40 coronary heart disease patients and 43 healthy controls by high-performance liquid chromatography coupled with mass spectrometry technology to find a set of effective biomarkers for CHD diagnosis and prognosis. The discriminating metabolites were extracted and analyzed by univariate and multivariate analysis methods. We found five metabolites (1-naphthol, 2-naphthol, methylitaconate, N-acetyl-d-glucosamine 6-phosphate and l-carnitine) contributing to the separation of CHD patients from healthy controls, and a subset of two metabolites in these five were identified as potential plasma biomarkers for CHD diagnosis. Major metabolic pathways associated with these potential biomarkers included nicotinate and nicotinamide metabolism, protein glycosylation, lipid metabolism and fatty acid metabolism. In addition, two potential biomarkers (GlcNAc-6-P and l-carnitine) were found be to be associated with intestinal microflora, indicating that intestinal microflora may be related to the metabolism and progression of CHD.}, }
@article {pmid27744226, year = {2017}, author = {Williams, DW and Gibson, G}, title = {Individualization of pubic hair bacterial communities and the effects of storage time and temperature.}, journal = {Forensic science international. Genetics}, volume = {26}, number = {}, pages = {12-20}, doi = {10.1016/j.fsigen.2016.09.006}, pmid = {27744226}, issn = {1878-0326}, mesh = {Coitus ; *Cryopreservation ; Female ; Genitalia, Female ; Genitalia, Male ; Hair/*microbiology ; Humans ; Male ; *Microbiota ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, RNA ; Specimen Handling/*methods ; *Temperature ; Time Factors ; }, abstract = {A potential application of microbial genetics in forensic science is detection of transfer of the pubic hair microbiome between individuals during sexual intercourse using high-throughput sequencing. In addition to the primary need to show whether the pubic hair microbiome is individualizing, one aspect that must be addressed before using the microbiome in criminal casework involves the impact of storage on the microbiome of samples recovered for forensic testing. To test the effects of short-term storage, pubic hair samples were collected from volunteers and stored at room temperature (∼20°C), refrigerated (4°C), and frozen (-20°C) for 1 week, 2 weeks, 4 weeks, and 6 weeks along with a baseline sample. Individual microbial profiles (R[2]=0.69) and gender (R[2]=0.17) were the greatest sources of variation between samples. Because of this variation, individual and gender could be predicted using Random Forests supervised classification in this sample set with an overall error rate of 2.7%± 5.8% and 1.7%±5.2%, respectively. There was no statistically significant difference attributable to time of sampling or temperature of storage within individuals. Further work on larger sample sets will quantify the temporal consistency of individual profiles and define whether it is plausible to detect transfer between sexual partners. For short-term storage (≤6 weeks), recovery of the microbiome was not affected significantly by either storage time or temperature, suggesting that investigators and crime laboratories can use existing evidence storage methods.}, }
@article {pmid27734124, year = {2017}, author = {Tu, Q and Li, J and Shi, Z and Chen, Y and Lin, L and Li, J and Wang, H and Yan, J and Zhou, Q and Li, X and Li, L and Zhou, J and He, Z}, title = {HuMiChip2 for strain level identification and functional profiling of human microbiomes.}, journal = {Applied microbiology and biotechnology}, volume = {101}, number = {1}, pages = {423-435}, doi = {10.1007/s00253-016-7910-0}, pmid = {27734124}, issn = {1432-0614}, mesh = {Humans ; Liver Cirrhosis ; Metagenomics/*methods ; Microarray Analysis/*methods ; Microbiological Techniques/*methods ; *Microbiota ; Nucleic Acid Hybridization/*methods ; Sensitivity and Specificity ; }, abstract = {With the massive data generated by the Human Microbiome Project, how to transform such data into useful information and knowledge remains challenging. Here, with currently available sequencing information (reference genomes and metagenomes), we have developed a comprehensive microarray, HuMiChip2, for strain-level identification and functional characterization of human microbiomes. HuMiChip2 was composed of 29,467 strain-specific probes targeting 2063 microbial strains/species and 133,924 sequence- and group-specific probes targeting 157 key functional gene families involved in various metabolic pathways and host-microbiome interaction processes. Computational evaluation of strain-specific probes suggested that they were not only specific to mock communities of sequenced microorganisms and metagenomes from different human body sites but also to non-sequenced microbial strains. Experimental evaluation of strain-specific probes using single strains/species and mock communities suggested a high specificity of these probes with their corresponding targets. Application of HuMiChip2 to human gut microbiome samples showed the patient microbiomes of alcoholic liver cirrhosis significantly (p < 0.05) shifted their functional structure from the healthy individuals, and the relative abundance of 21 gene families significantly (p < 0.1) differed between the liver cirrhosis patients and healthy individuals. At the strain level, five Bacteroides strains were significantly (p < 0.1) and more frequently detected in liver cirrhosis patients. These results suggest that the developed HuMiChip2 is a useful microbial ecological microarray for both strain-level identification and functional profiling of human microbiomes.}, }
@article {pmid27729053, year = {2016}, author = {Rhodes, R}, title = {Ethical issues in microbiome research and medicine.}, journal = {BMC medicine}, volume = {14}, number = {1}, pages = {156}, pmid = {27729053}, issn = {1741-7015}, support = {R01 HG004856/HG/NHGRI NIH HHS/United States ; }, mesh = {*Ethics, Research ; Humans ; *Microbiota ; }, abstract = {The human microbiome is the collection of bacteria, viruses, and fungi that live on and in the human organism's skin, mucosa, and intestinal tract. Re-examining commonly accepted ethical standards from the perspective of this new area of research provides an opportunity to reassess our current thinking about research regulations as well as the importance of some principles and distinctions. In this commentary, I explain ethical issues illuminated by research on the human microbiome related to personal identity, privacy, property, research ethics, public health, and biobanks.}, }
@article {pmid27726809, year = {2016}, author = {Aboudharam, G}, title = {Sources of Materials for Paleomicrobiology.}, journal = {Microbiology spectrum}, volume = {4}, number = {4}, pages = {}, doi = {10.1128/microbiolspec.PoH-0016-2015}, pmid = {27726809}, issn = {2165-0497}, mesh = {Animals ; Archaea/genetics ; Bacteria/genetics ; Communicable Diseases/*diagnosis/*microbiology ; DNA/genetics/*isolation &amp; purification ; *Fossils ; Humans ; Microbiological Techniques/*methods ; Paleopathology/*methods ; Parasites/genetics ; Specimen Handling/*methods ; Viruses/genetics ; }, abstract = {The Paleomicrobiology establishes the diagnosis of ancient infectious diseases by studying ancient pathogens. This recent science also analyzes the evolution of these pathogens, virulence, and their adaptation to their habitat and their vectors. The DNA persists a long time after the death of an organism despite the chemical and enzymatic degradation. The possibility of sequencing bacterial, viral, parasitic and archaeal DNA molecules persists over time.Various sources are used for these studies: frozen tissue and particularly human tissue are a exceptional source for the analysis because at very low temperatures, all biological activity is suspended. The coprolites are a source of choice for studying the human microbiome. Other sources, the ancient bones are the most abundant, however, they may contain only small amounts of DNA due to natural leaching. When the use of the tooth is possible, is a particularly interesting source because of its highly mineralized structure, which gives greater persistence than bone. The calcified tartar deposited on teeth is a source of interest for the study of oral microbiome.All these sources are subject to precautions (gloves and masks hat) at the time of sampling to avoid cross contamination and also be listed in the most precise way because they are precious and rare.}, }
@article {pmid27725817, year = {2016}, author = {Lukiw, WJ}, title = {Bacteroides fragilis Lipopolysaccharide and Inflammatory Signaling in Alzheimer's Disease.}, journal = {Frontiers in microbiology}, volume = {7}, number = {}, pages = {1544}, pmid = {27725817}, issn = {1664-302X}, support = {R01 AG018031/AG/NIA NIH HHS/United States ; R01 AG038834/AG/NIA NIH HHS/United States ; R01 EY006311/EY/NEI NIH HHS/United States ; }, abstract = {The human microbiome consists of ~3.8 × 10[13] symbiotic microorganisms that form a highly complex and dynamic ecosystem: the gastrointestinal (GI) tract constitutes the largest repository of the human microbiome by far, and its impact on human neurological health and disease is becoming increasingly appreciated. Bacteroidetes, the largest phylum of Gram-negative bacteria in the GI tract microbiome, while generally beneficial to the host when confined to the GI tract, have potential to secrete a remarkably complex array of pro-inflammatory neurotoxins that include surface lipopolysaccharides (LPSs) and toxic proteolytic peptides. The deleterious effects of these bacterial exudates appear to become more important as GI tract and blood-brain barriers alter or increase their permeability with aging and disease. For example, presence of the unique LPSs of the abundant Bacteroidetes species Bacteroides fragilis (BF-LPS) in the serum represents a major contributing factor to systemic inflammation. BF-LPS is further recognized by TLR2, TLR4, and/or CD14 microglial cell receptors as are the pro-inflammatory 42 amino acid amyloid-beta (Aβ42) peptides that characterize Alzheimer's disease (AD) brain. Here we provide the first evidence that BF-LPS exposure to human primary brain cells is an exceptionally potent inducer of the pro-inflammatory transcription factor NF-kB (p50/p65) complex, a known trigger in the expression of pathogenic pathways involved in inflammatory neurodegeneration. This 'Perspectives communication' will in addition highlight work from recent studies that advance novel and emerging concepts on the potential contribution of microbiome-generated factors, such as BF-LPS, in driving pro-inflammatory degenerative neuropathology in the AD brain.}, }
@article {pmid27725814, year = {2016}, author = {Levi Mortera, S and Del Chierico, F and Vernocchi, P and Rosado, MM and Cavola, A and Chierici, M and Pieroni, L and Urbani, A and Carsetti, R and Lante, I and Dallapiccola, B and Putignani, L}, title = {Monitoring Perinatal Gut Microbiota in Mouse Models by Mass Spectrometry Approaches: Parental Genetic Background and Breastfeeding Effects.}, journal = {Frontiers in microbiology}, volume = {7}, number = {}, pages = {1523}, pmid = {27725814}, issn = {1664-302X}, abstract = {At birth, contact with external stimuli, such as nutrients derived from food, is necessary to modulate the symbiotic balance between commensal and pathogenic bacteria, protect against bacterial dysbiosis, and initiate the development of the mucosal immune response. Among a variety of different feeding patterns, breastfeeding represents the best modality. In fact, the capacity of breast milk to modulate the composition of infants' gut microbiota leads to beneficial effects on their health. In this study, we used newborn mice as a model to evaluate the effect of parental genetic background (i.e., IgA-producing mice and IgA-deficient mice) and feeding modulation (i.e., maternal feeding and cross-feeding) on the onset and shaping of gut microbiota after birth. To investigate these topics, we used either a culturomic approach that employed Matrix Assisted Laser Desorption Ionization Time-of-Flight Mass Spectrometry (MS), or bottom-up Liquid Chromatography, with subsequent MSMS shotgun metaproteomic analysis that compared and assembled results of the two techniques. We found that the microbial community was enriched by lactic acid bacteria when pups were breastfed by wild-type (WT) mothers, while IgA-deficient milk led to an increase in the opportunistic bacterial pathogen (OBP) population. Cross-feeding results suggested that IgA supplementation promoted the exclusion of some OBPs and the temporary appearance of beneficial species in pups fed by WT foster mothers. Our results show that both techniques yield a picture of microbiota from different angles and with varying depths. In particular, our metaproteomic pipeline was found to be a reliable tool in the description of microbiota. Data from these studies are available via ProteomeXchange, with identifier PXD004033.}, }
@article {pmid27719998, year = {2016}, author = {Younger, DS}, title = {I-Cubed (Infection, Immunity, and Inflammation) and the Human Microbiome.}, journal = {Neurologic clinics}, volume = {34}, number = {4}, pages = {863-874}, doi = {10.1016/j.ncl.2016.05.006}, pmid = {27719998}, issn = {1557-9875}, mesh = {Humans ; Immunity/immunology/*physiology ; Infections/epidemiology/*microbiology/physiopathology ; Inflammation/epidemiology/*microbiology/physiopathology ; Microbiota/genetics/*physiology ; }, abstract = {Medical science is just now realizing the full importance of the microbial world. Thanks to developments such as low-cost high-throughput sequencing of microbial communities comprising the human microbiome, the identity and function of unculturable microbes are being unveiled. Public health officials and neuroepidemiology researchers will be called on to guide the understanding of I-Cubed illnesses and the implications of the human microbiome for communicable and noncommunicable diseases, as the natural history is appreciated and the responsiveness of given medical and neurologic disorders to a variety of medical approaches, including strong antibiotics and immune-modulatory therapy is established.}, }
@article {pmid27717408, year = {2016}, author = {Pal, C and Bengtsson-Palme, J and Kristiansson, E and Larsson, DG}, title = {The structure and diversity of human, animal and environmental resistomes.}, journal = {Microbiome}, volume = {4}, number = {1}, pages = {54}, pmid = {27717408}, issn = {2049-2618}, mesh = {Animals ; Anti-Bacterial Agents/*pharmacology ; Bacteria/drug effects/*genetics ; Drug Resistance, Multiple, Bacterial/*genetics ; Gastrointestinal Microbiome/drug effects/*genetics ; Gene Transfer, Horizontal ; Genes, Bacterial/*genetics ; High-Throughput Nucleotide Sequencing ; Humans ; Interspersed Repetitive Sequences/*genetics ; Metals/pharmacology ; Selection, Genetic/drug effects/*genetics ; Sewage/microbiology ; Smog ; Soil Microbiology ; Tetracycline Resistance/genetics ; }, abstract = {BACKGROUND: Antibiotic resistance genes (ARGs) are widespread but cause problems only when present in pathogens. Environments where selection and transmission of antibiotic resistance frequently take place are likely to be characterized by high abundance and diversity of horizontally transferable ARGs. Large-scale quantitative data on ARGs is, however, lacking for most types of environments, including humans and animals, as is data on resistance genes to potential co-selective agents, such as biocides and metals. This paucity prevents efficient identification of risk environments.<br><br>RESULTS: We provide a comprehensive characterization of resistance genes, mobile genetic elements (MGEs) and bacterial taxonomic compositions for 864 metagenomes from humans (n&#x2009;=&#x2009;350), animals (n&#x2009;=&#x2009;145) and external environments (n&#x2009;=&#x2009;369), all deeply sequenced using Illumina technology. Environment types showed clear differences in both resistance profiles and bacterial community compositions. Human and animal microbial communities were characterized by limited taxonomic diversity and low abundance and diversity of biocide/metal resistance genes and MGEs but a relatively high abundance of ARGs. In contrast, external environments showed consistently high taxonomic diversity which in turn was linked to high diversity of both biocide/metal resistance genes and MGEs. Water, sediment and soil generally carried low relative abundance and few varieties of known ARGs, whereas wastewater/sludge was on par with the human gut. The environments with the largest relative abundance and/or diversity of ARGs, including genes encoding resistance to last resort antibiotics, were those subjected to industrial antibiotic pollution and a limited set of deeply sequenced air samples from a Beijing smog event.<br><br>CONCLUSIONS: Our study identifies air and antibiotic-polluted environments as under-investigated transmission routes and reservoirs for antibiotic resistance. The high taxonomic and genetic diversity of external environments supports the hypothesis that these also form vast sources of unknown resistance genes, with potential to be transferred to pathogens in the future.}, }
@article {pmid27701448, year = {2016}, author = {Kia, E and Wagner Mackenzie, B and Middleton, D and Lau, A and Waite, DW and Lewis, G and Chan, YK and Silvestre, M and Cooper, GJ and Poppitt, SD and Taylor, MW}, title = {Integrity of the Human Faecal Microbiota following Long-Term Sample Storage.}, journal = {PloS one}, volume = {11}, number = {10}, pages = {e0163666}, pmid = {27701448}, issn = {1932-6203}, mesh = {Biodiversity ; DNA, Bacterial ; Feces/*microbiology ; Humans ; Metagenome ; Metagenomics ; *Microbial Viability ; *Microbiota ; *Preservation, Biological ; RNA, Ribosomal, 16S ; Time Factors ; }, abstract = {In studies of the human microbiome, faecal samples are frequently used as a non-invasive proxy for the study of the intestinal microbiota. To obtain reliable insights, the need for bacterial DNA of high quality and integrity following appropriate faecal sample collection and preservation steps is paramount. In a study of dietary mineral balance in the context of type 2 diabetes (T2D), faecal samples were collected from healthy and T2D individuals throughout a 13-day residential trial. These samples were freeze-dried, then stored mostly at -20°C from the trial date in 2000/2001 until the current research in 2014. Given the relative antiquity of these samples (~14 years), we sought to evaluate DNA quality and comparability to freshly collected human faecal samples. Following the extraction of bacterial DNA, gel electrophoresis indicated that our DNA extracts were more sheared than extracts made from freshly collected faecal samples, but still of sufficiently high molecular weight to support amplicon-based studies. Likewise, spectrophotometric assessment of extracts revealed that they were of high quality and quantity. A subset of bacterial 16S rRNA gene amplicons were sequenced using Illumina MiSeq and compared against publicly available sequence data representing a similar cohort analysed by the American Gut Project (AGP). Notably, our bacterial community profiles were highly consistent with those from the AGP data. Our results suggest that when faecal specimens are stored appropriately, the microbial profiles are preserved and robust to extended storage periods.}, }
@article {pmid27698620, year = {2016}, author = {Bik, EM}, title = {The Hoops, Hopes, and Hypes of Human Microbiome Research.}, journal = {The Yale journal of biology and medicine}, volume = {89}, number = {3}, pages = {363-373}, pmid = {27698620}, issn = {1551-4056}, mesh = {Autistic Disorder/genetics ; Computational Biology/methods ; Humans ; Inflammatory Bowel Diseases/genetics ; Microbiota/*genetics ; }, abstract = {Recent developments in sequencing methods and bioinformatics analysis tools have greatly enabled the culture-independent analysis of complex microbial communities associated with environmental samples, plants, and animals. This has led to a spectacular increase in the number of studies on both membership and functionalities of these hitherto invisible worlds, in particular those of the human microbiome. The wide variety in available microbiome tools and platforms can be overwhelming, and making sound conclusions from scientific research can be challenging. Here, I will review 1) the methodological and analytic hoops a good microbiome study has to jump through, including DNA extraction and choice of bioinformatics tools, 2) the hopes this field has generated for diseases such as autism and inflammatory bowel diseases, and 3) some of the hypes that it has created, e.g., by confusing correlation and causation, and the recent pseudoscientific commercialization of microbiome research.}, }
@article {pmid27698613, year = {2016}, author = {Jones, RM}, title = {The Influence of the Gut Microbiota on Host Physiology: In Pursuit of Mechanisms.}, journal = {The Yale journal of biology and medicine}, volume = {89}, number = {3}, pages = {285-297}, pmid = {27698613}, issn = {1551-4056}, support = {R01 DK098391/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Bacteria/metabolism ; Gastrointestinal Microbiome/*physiology ; Humans ; Intestines/microbiology ; Probiotics/metabolism ; Stem Cells/immunology/metabolism ; }, abstract = {The results generated from the NIH funded Human Microbiome Project (HMP) are necessarily tied to the overall mission of the agency, which is to foster scientific discoveries as a basis for protecting and improving health. The investment in the HMP phase 1 accomplished many of its goals including the preliminary characterization of the human microbiome and the identification of links between microbiome diversity and disease states. Going forward, the next step in these studies must involve the identification of the functional molecular elements that mediate the positive influence of a eubiotic microbiome on health and disease. This review will focus on recent advances describing mechanistic events in the intestine elicited by the microbiome. These include symbiotic bacteria-induced activation of redox-dependent cell signaling, the bacterial production of short chain fatty acids and ensuing cellular responses, and the secretion of bacteriocins by bacteria that have anti-microbial activities against potential pathogens.}, }
@article {pmid27698612, year = {2016}, author = {Smith, BC and Zolnik, CP and Usyk, M and Chen, Z and Kaiser, K and Nucci-Sack, A and Peake, K and Diaz, A and Viswanathan, S and Strickler, HD and Schlecht, NF and Burk, RD}, title = {Distinct Ecological Niche of Anal, Oral, and Cervical Mucosal Microbiomes in Adolescent Women.}, journal = {The Yale journal of biology and medicine}, volume = {89}, number = {3}, pages = {277-284}, pmid = {27698612}, issn = {1551-4056}, support = {K12 GM102779/GM/NIGMS NIH HHS/United States ; R01 AI072204/AI/NIAID NIH HHS/United States ; }, mesh = {Adolescent ; Adult ; Anal Canal/*microbiology ; Cervix Mucus/*microbiology ; Child ; Computational Biology ; Female ; Humans ; Microbiota/physiology ; Mouth/*microbiology ; Sequence Analysis, DNA ; Young Adult ; }, abstract = {Human body sites represent ecological niches for microorganisms, each providing variations in microbial exposure, nutrient availability, microbial competition, and host immunological responses. In this study, we investigated the oral, anal, and cervical microbiomes from the same 20 sexually active adolescent females, using culture-independent, next-generation sequencing. DNA from each sample was amplified for the bacterial 16S rRNA gene and sequenced on an Illumina platform using paired-end reads. Across the three anatomical niches, we found significant differences in bacterial community composition and diversity. Overall anal samples were dominated with Prevotella and Bacteriodes, oral samples with Streptococcus and Prevotella, and cervical samples with Lactobacillus. The microbiomes of a few cervical samples clustered with anal samples in weighted principal coordinate analyses, due in part to a higher proportion of Prevotella in those samples. Additionally, cervical samples had the lowest alpha diversity. Our results demonstrate the occurrence of distinct microbial communities across body sites within the same individual.}, }
@article {pmid27697111, year = {2016}, author = {Moon, JH and Lee, JH}, title = {Probing the diversity of healthy oral microbiome with bioinformatics approaches.}, journal = {BMB reports}, volume = {49}, number = {12}, pages = {662-670}, pmid = {27697111}, issn = {1976-670X}, mesh = {Aging ; Bacteria/genetics ; Climate ; *Computational Biology ; Databases, Genetic ; Humans ; *Microbiota ; Mouth/*microbiology ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; }, abstract = {The human oral cavity contains a highly personalized microbiome essential to maintaining health, but capable of causing oral and systemic diseases. Thus, an in-depth definition of "healthy oral microbiome" is critical to understanding variations in disease states from preclinical conditions, and disease onset through progressive states of disease. With rapid advances in DNA sequencing and analytical technologies, population-based studies have documented the range and diversity of both taxonomic compositions and functional potentials observed in the oral microbiome in healthy individuals. Besides factors specific to the host, such as age and race/ethnicity, environmental factors also appear to contribute to the variability of the healthy oral microbiome. Here, we review bioinformatic techniques for metagenomic datasets, including their strengths and limitations. In addition, we summarize the interpersonal and intrapersonal diversity of the oral microbiome, taking into consideration the recent large-scale and longitudinal studies, including the Human Microbiome Project. [BMB Reports 2016; 49(12): 662-670].}, }
@article {pmid27684630, year = {2016}, author = {Kim, HJ and Lee, J and Choi, JH and Bahinski, A and Ingber, DE}, title = {Co-culture of Living Microbiome with Microengineered Human Intestinal Villi in a Gut-on-a-Chip Microfluidic Device.}, journal = {Journal of visualized experiments : JoVE}, volume = {}, number = {114}, pages = {}, pmid = {27684630}, issn = {1940-087X}, abstract = {Here, we describe a protocol to perform long-term co-culture of multi-species human gut microbiome with microengineered intestinal villi in a human gut-on-a-chip microphysiological device. We recapitulate the intestinal lumen-capillary tissue interface in a microfluidic device, where physiological mechanical deformations and fluid shear flow are constantly applied to mimic peristalsis. In the lumen microchannel, human intestinal epithelial Caco-2 cells are cultured to form a 'germ-free' villus epithelium and regenerate small intestinal villi. Pre-cultured microbial cells are inoculated into the lumen side to establish a host-microbe ecosystem. After microbial cells adhere to the apical surface of the villi, fluid flow and mechanical deformations are resumed to produce a steady-state microenvironment in which fresh culture medium is constantly supplied and unbound bacteria (as well as bacterial wastes) are continuously removed. After extended co-culture from days to weeks, multiple microcolonies are found to be randomly located between the villi, and both microbial and epithelial cells remain viable and functional for at least one week in culture. Our co-culture protocol can be adapted to provide a versatile platform for other host-microbiome ecosystems that can be found in various human organs, which may facilitate in vitro study of the role of human microbiome in orchestrating health and disease.}, }
@article {pmid27679525, year = {2017}, author = {Fitzstevens, JL and Smith, KC and Hagadorn, JI and Caimano, MJ and Matson, AP and Brownell, EA}, title = {Systematic Review of the Human Milk Microbiota.}, journal = {Nutrition in clinical practice : official publication of the American Society for Parenteral and Enteral Nutrition}, volume = {32}, number = {3}, pages = {354-364}, doi = {10.1177/0884533616670150}, pmid = {27679525}, issn = {1941-2452}, mesh = {*Food Microbiology ; Humans ; Infant ; *Microbiota ; Milk, Human/*microbiology ; Staphylococcus/classification/isolation &amp; purification ; Streptococcus/classification/isolation &amp; purification ; }, abstract = {Human milk-associated microbes are among the first to colonize the infant gut and may help to shape both short- and long-term infant health outcomes. We performed a systematic review to characterize the microbiota of human milk. Relevant primary studies were identified through a comprehensive search of PubMed (January 1, 1964, to June 31, 2015). Included studies were conducted among healthy mothers, were written in English, identified bacteria in human milk, used culture-independent methods, and reported primary results at the genus level. Twelve studies satisfied inclusion criteria. All varied in geographic location and human milk collection/storage/analytic methods. Streptococcus was identified in human milk samples in 11 studies (91.6%) and Staphylococcus in 10 (83.3%); both were predominant genera in 6 (50%). Eight of the 12 studies used conventional ribosomal RNA (rRNA) polymerase chain reaction (PCR), of which 7 (87.5%) identified Streptococcus and 6 (80%) identified Staphylococcus as present. Of these 8 studies, 2 (25%) identified Streptococcus and Staphylococcus as predominant genera. Four of the 12 studies used next-generation sequencing (NGS), all of which identified Streptococcus and Staphylococcus as present and predominant genera. Relative to conventional rRNA PCR, NGS is a more sensitive method to identify/quantify bacterial genera in human milk, suggesting the predominance of Streptococcus and Staphylococcus may be underestimated in studies using older methods. These genera, Streptococcus and Staphylococcus, may be universally predominant in human milk, regardless of differences in geographic location or analytic methods. Primary studies designed to evaluate the effect of these 2 genera on short- and long-term infant outcomes are warranted.}, }
@article {pmid27668170, year = {2016}, author = {Sung, J and Hale, V and Merkel, AC and Kim, PJ and Chia, N}, title = {Metabolic modeling with Big Data and the gut microbiome.}, journal = {Applied &amp; translational genomics}, volume = {10}, number = {}, pages = {10-15}, pmid = {27668170}, issn = {2212-0661}, support = {R01 CA179243/CA/NCI NIH HHS/United States ; }, abstract = {The recent advances in high-throughput omics technologies have enabled researchers to explore the intricacies of the human microbiome. On the clinical front, the gut microbial community has been the focus of many biomarker-discovery studies. While the recent deluge of high-throughput data in microbiome research has been vastly informative and groundbreaking, we have yet to capture the full potential of omics-based approaches. Realizing the promise of multi-omics data will require integration of disparate omics data, as well as a biologically relevant, mechanistic framework - or metabolic model - on which to overlay these data. Also, a new paradigm for metabolic model evaluation is necessary. Herein, we outline the need for multi-omics data integration, as well as the accompanying challenges. Furthermore, we present a framework for characterizing the ecology of the gut microbiome based on metabolic network modeling.}, }
@article {pmid27662587, year = {2016}, author = {Lavelle, A and Lennon, G and Winter, DC and O'Connell, PR}, title = {Colonic biogeography in health and ulcerative colitis.}, journal = {Gut microbes}, volume = {7}, number = {5}, pages = {435-442}, pmid = {27662587}, issn = {1949-0984}, mesh = {Animals ; Bacteria/classification/genetics/*isolation &amp; purification ; Colitis, Ulcerative/immunology/*microbiology ; Colon/immunology/*microbiology ; *Gastrointestinal Microbiome ; Health ; Humans ; Phylogeny ; }, abstract = {The relevance of biogeography to the distal gut microbiota has been investigated in both health and inflammatory bowel disease (IBD), however multiple factors, including sample type and methodology, microbiota characterization and interpersonal variability make the construction of a core model of colonic biogeography challenging. In addition, how phylogenetic classification relates to immunogenicity and whether consistent alterations in the microbiota are associated with ulcerative colitis (UC) remain open questions. This addendum seeks to review the human colonic microbiota in health and UC as currently understood, in the broader context of the human microbiome.}, }
@article {pmid27650128, year = {2016}, author = {Verwoerd, A and Ter Haar, NM and de Roock, S and Vastert, SJ and Bogaert, D}, title = {The human microbiome and juvenile idiopathic arthritis.}, journal = {Pediatric rheumatology online journal}, volume = {14}, number = {1}, pages = {55}, pmid = {27650128}, issn = {1546-0096}, mesh = {*Arthritis, Juvenile/immunology/microbiology ; *Autoimmunity ; Humans ; Microbiota/*immunology ; }, abstract = {Juvenile idiopathic arthritis (JIA) is the most common rheumatic disease in childhood. The pathogenesis of JIA is thought to be the result of a combination of host genetic and environmental triggers. However, the precise factors that determine one's susceptibility to JIA remain to be unravelled. The microbiome has received increasing attention as a potential contributing factor to the development of a wide array of immune-mediated diseases, including inflammatory bowel disease, type 1 diabetes and rheumatoid arthritis. Also in JIA, there is accumulating evidence that the composition of the microbiome is different from healthy individuals. A growing body of evidence indeed suggests that, among others, the microbiome may influence the development of the immune system, the integrity of the intestinal mucosal barrier, and the differentiation of T cell subsets. In turn, this might lead to dysregulation of the immune system, thereby possibly playing a role in the development of JIA. The potential to manipulate the microbiome, for example by faecal microbial transplantation, might then offer perspectives for future therapeutic interventions. Before we can think of such interventions, we need to first obtain a deeper understanding of the cause and effect relationship between JIA and the microbiome. In this review, we discuss the existing evidence for the involvement of the microbiome in JIA pathogenesis and explore the potential mechanisms through which the microbiome may influence the development of autoimmunity in general and JIA specifically.}, }
@article {pmid27643883, year = {2016}, author = {Salk, HM and Simon, WL and Lambert, ND and Kennedy, RB and Grill, DE and Kabat, BF and Poland, GA}, title = {Taxa of the Nasal Microbiome Are Associated with Influenza-Specific IgA Response to Live Attenuated Influenza Vaccine.}, journal = {PloS one}, volume = {11}, number = {9}, pages = {e0162803}, pmid = {27643883}, issn = {1932-6203}, mesh = {Adolescent ; Adult ; Antibodies, Viral/immunology ; Bacteria/classification/*immunology ; Female ; Hemagglutinin Glycoproteins, Influenza Virus/immunology ; Humans ; Immunoglobulin A/*immunology ; Influenza A virus/*immunology ; Influenza Vaccines/*immunology ; Influenza, Human/immunology/microbiology/*prevention &amp; control ; Male ; *Microbiota ; Nasal Cavity/*microbiology ; Vaccines, Attenuated/*immunology ; Young Adult ; }, abstract = {Live attenuated influenza vaccine (LAIV) has demonstrated varying levels of efficacy against seasonal influenza; however, LAIV may be used as a tool to measure interactions between the human microbiome and a live, replicating virus. To increase our knowledge of this interaction, we measured changes to the nasal microbiome in subjects who received LAIV to determine if associations between influenza-specific IgA production and the nasal microbiome exist after immunization with a live virus vaccine. The anterior nares of 47 healthy subjects were swabbed pre- (Day 0) and post- (Days 7 and 28) LAIV administration, and nasal washes were conducted on Days 0 and 28. We performed next-generation sequencing on amplified 16s rRNA genes and measured mucosal influenza-specific IgA titers via enzyme-linked immunosorbent assay (ELISA). A significant increase in alpha diversity was identified (Observed, CHAO, and ACE) between Days 7 vs 0 (p-values = 0.017, 0.005, 0.005, respectively) and between Days 28 vs 0 (p-values = 0.054, 0.030, 0.050, respectively). Several significant associations between the presence of different microbial species, including Lactobacillus helveticus, Prevotella melaninogenica, Streptococcus infantis, Veillonella dispar, and Bacteroides ovatus, and influenza-specific H1 and H3 IgA antibody response were demonstrated. These data suggest that LAIV alters the nasal microbiome, allowing several less-abundant OTUs to establish a community niche. Additionally, specific alterations in the nasal microbiome are significantly associated with variations in influenza-specific IgA antibody production and could be clinically relevant.}, }
@article {pmid27634185, year = {2016}, author = {Severance, EG and Tveiten, D and Lindström, LH and Yolken, RH and Reichelt, KL}, title = {The Gut Microbiota and the Emergence of Autoimmunity: Relevance to Major Psychiatric Disorders.}, journal = {Current pharmaceutical design}, volume = {22}, number = {40}, pages = {6076-6086}, pmid = {27634185}, issn = {1873-4286}, support = {P50 MH094268/MH/NIMH NIH HHS/United States ; }, mesh = {Animals ; *Autoimmunity ; Gastrointestinal Microbiome/*immunology ; Humans ; Mental Disorders/*immunology ; }, abstract = {BACKGROUND: Autoimmune phenotypes are prevalent in major psychiatric disorders. Disequilibria of cellular processes occurring in the gastrointestinal (GI) tract likely contribute to immune dysfunction in psychiatric disorders. As the venue of a complex community of resident microbes, the gut in a homeostatic state equates with a functional digestive system, cellular barrier stability and properly regulated recognition of self and non-self antigens. When gut processes become disrupted as a result of environmental or genetic factors, autoimmunity may ensue.<br><br>METHODS: Here, we review the issues pertinent to autoimmunity and the microbiome in psychiatric disorders and show that many of the reported immune risk factors for the development of these brain disorders are in fact related and consistent with dysfunctions occurring in the gut. We review the few human microbiome studies that have been done in people with psychiatric disorders and supplement this information with mechanistic data gleaned from experimental rodent studies.<br><br>RESULTS: These investigations demonstrate changes in behavior and brain biochemistry directly attributable to alterations in the gut microbiome. We present a model by which autoantigens are produced by extrinsicallyderived food and microbial factors bound to intrinsic components of the gut including receptors present in the enteric nervous system.<br><br>CONCLUSION: This new focus on examining activities outside of the CNS for relevance to the etiology and pathophysiology of psychiatric disorders may require new modalities or a re-evaluation of pharmaceutical targets found in peripheral systems.}, }
@article {pmid27608937, year = {2016}, author = {Hong, BY and Maulén, NP and Adami, AJ and Granados, H and Balcells, ME and Cervantes, J}, title = {Microbiome Changes during Tuberculosis and Antituberculous Therapy.}, journal = {Clinical microbiology reviews}, volume = {29}, number = {4}, pages = {915-926}, pmid = {27608937}, issn = {1098-6618}, support = {F30 HL126324/HL/NHLBI NIH HHS/United States ; }, mesh = {Antitubercular Agents/*therapeutic use ; Dysbiosis ; Humans ; Microbiota/*drug effects ; Respiratory System/*microbiology ; Tuberculosis/*drug therapy ; }, abstract = {The critical role of commensal microbiota in the human body has been increasingly recognized, and our understanding of its implications in human health and disease has expanded rapidly. The lower respiratory tract contains diverse communities of microbes known as lung microbiota, which are present in healthy individuals and in individuals with respiratory diseases. The dysbiosis of the airway microbiota in pulmonary tuberculosis (TB) may play a role in the pathophysiological processes associated with TB disease. Recent studies of the lung microbiome have pointed out changes in lung microbial communities associated with TB and other lung diseases and have also begun to elucidate the profound effects that antituberculous drug therapy can have on the human lung microbiome composition. In this review, the potential role of the human microbiome in TB pathogenesis and the changes in the human microbiome with Mycobacterium tuberculosis infection and TB therapy are presented and discussed.}, }
@article {pmid27606010, year = {2016}, author = {McMillan, A and Renaud, JB and Gloor, GB and Reid, G and Sumarah, MW}, title = {Post-acquisition filtering of salt cluster artefacts for LC-MS based human metabolomic studies.}, journal = {Journal of cheminformatics}, volume = {8}, number = {1}, pages = {44}, pmid = {27606010}, issn = {1758-2946}, abstract = {Liquid chromatography-high resolution mass spectrometry (LC-MS) has emerged as one of the most widely used platforms for untargeted metabolomics due to its unparalleled sensitivity and metabolite coverage. Despite its prevalence of use, the proportion of true metabolites identified in a given experiment compared to background contaminants and ionization-generated artefacts remains poorly understood. Salt clusters are well documented artefacts of electrospray ionization MS, recognized by their characteristically high mass defects (for this work simply generalized as the decimal numbers after the nominal mass). Exploiting this property, we developed a method to identify and remove salt clusters from LC-MS-based human metabolomics data using mass defect filtering. By comparing the complete set of endogenous metabolites in the human metabolome database to actual plasma, urine and stool samples, we demonstrate that up to 28.5 % of detected features are likely salt clusters. These clusters occur irrespective of ionization mode, column type, sweep gas and sample type, but can be easily removed post-acquisition using a set of R functions presented here. Our mass defect filter removes unwanted noise from LC-MS metabolomics datasets, while retaining true metabolites, and requires only a list of m/z and retention time values. Reducing the number of features prior to statistical analyses will result in more accurate multivariate modeling and differential feature selection, as well as decreased reporting of unknowns that often constitute the largest proportion of human metabolomics data.}, }
@article {pmid27574119, year = {2017}, author = {Millman, A and Dar, D and Shamir, M and Sorek, R}, title = {Computational prediction of regulatory, premature transcription termination in bacteria.}, journal = {Nucleic acids research}, volume = {45}, number = {2}, pages = {886-893}, pmid = {27574119}, issn = {1362-4962}, support = {260432/ERC_/European Research Council/International ; }, mesh = {Bacteria/*genetics ; *Computer Simulation ; *Gene Expression Regulation, Bacterial ; Machine Learning ; *Models, Biological ; Nucleic Acid Conformation ; RNA, Messenger/chemistry/genetics ; ROC Curve ; *Transcription Termination, Genetic ; }, abstract = {A common strategy for regulation of gene expression in bacteria is conditional transcription termination. This strategy is frequently employed by 5'UTR cis-acting RNA elements (riboregulators), including riboswitches and attenuators. Such riboregulators can assume two mutually exclusive RNA structures, one of which forms a transcriptional terminator and results in premature termination, and the other forms an antiterminator that allows read-through into the coding sequence to produce a full-length mRNA. We developed a machine-learning based approach, which, given a 5'UTR of a gene, predicts whether it can form the two alternative structures typical to riboregulators employing conditional termination. Using a large positive training set of riboregulators derived from 89 human microbiome bacteria, we show high specificity and sensitivity for our classifier. We further show that our approach allows the discovery of previously unidentified riboregulators, as exemplified by the detection of new LeuA leaders and T-boxes in Streptococci Finally, we developed PASIFIC (www.weizmann.ac.il/molgen/Sorek/PASIFIC/), an online web-server that, given a user-provided 5'UTR sequence, predicts whether this sequence can adopt two alternative structures conforming with the conditional termination paradigm. This webserver is expected to assist in the identification of new riboswitches and attenuators in the bacterial pan-genome.}, }
@article {pmid27573830, year = {2016}, author = {Clayton, JB and Vangay, P and Huang, H and Ward, T and Hillmann, BM and Al-Ghalith, GA and Travis, DA and Long, HT and Tuan, BV and Minh, VV and Cabana, F and Nadler, T and Toddes, B and Murphy, T and Glander, KE and Johnson, TJ and Knights, D}, title = {Captivity humanizes the primate microbiome.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {113}, number = {37}, pages = {10376-10381}, pmid = {27573830}, issn = {1091-6490}, support = {T32 DA007097/DA/NIDA NIH HHS/United States ; UL1 TR000114/TR/NCATS NIH HHS/United States ; }, mesh = {Animals ; Bacteria/classification/genetics ; Diet ; Gastrointestinal Microbiome/*genetics ; Gastrointestinal Tract/*microbiology ; *Genetic Variation ; Humans ; Phylogeny ; Primates/genetics/*microbiology ; RNA, Ribosomal, 16S/genetics ; }, abstract = {The primate gastrointestinal tract is home to trillions of bacteria, whose composition is associated with numerous metabolic, autoimmune, and infectious human diseases. Although there is increasing evidence that modern and Westernized societies are associated with dramatic loss of natural human gut microbiome diversity, the causes and consequences of such loss are challenging to study. Here we use nonhuman primates (NHPs) as a model system for studying the effects of emigration and lifestyle disruption on the human gut microbiome. Using 16S rRNA gene sequencing in two model NHP species, we show that although different primate species have distinctive signature microbiota in the wild, in captivity they lose their native microbes and become colonized with Prevotella and Bacteroides, the dominant genera in the modern human gut microbiome. We confirm that captive individuals from eight other NHP species in a different zoo show the same pattern of convergence, and that semicaptive primates housed in a sanctuary represent an intermediate microbiome state between wild and captive. Using deep shotgun sequencing, chemical dietary analysis, and chloroplast relative abundance, we show that decreasing dietary fiber and plant content are associated with the captive primate microbiome. Finally, in a meta-analysis including published human data, we show that captivity has a parallel effect on the NHP gut microbiome to that of Westernization in humans. These results demonstrate that captivity and lifestyle disruption cause primates to lose native microbiota and converge along an axis toward the modern human microbiome.}, }
@article {pmid27572971, year = {2016}, author = {Donati, C and Zolfo, M and Albanese, D and Tin Truong, D and Asnicar, F and Iebba, V and Cavalieri, D and Jousson, O and De Filippo, C and Huttenhower, C and Segata, N}, title = {Uncovering oral Neisseria tropism and persistence using metagenomic sequencing.}, journal = {Nature microbiology}, volume = {1}, number = {7}, pages = {16070}, pmid = {27572971}, issn = {2058-5276}, support = {R01 HG005969/HG/NHGRI NIH HHS/United States ; U54 DE023798/DE/NIDCR NIH HHS/United States ; }, mesh = {Computers, Molecular ; Genome, Bacterial ; Gingiva/microbiology ; Humans ; *Metagenome ; Metagenomics/methods ; Microbiota ; Mouth/*microbiology ; Multilocus Sequence Typing ; Neisseria/classification/genetics/isolation &amp; purification/*physiology ; Pharynx/microbiology ; Phylogeny ; Polymorphism, Single Nucleotide ; *Sequence Analysis, DNA ; Tongue/microbiology ; *Viral Tropism ; }, abstract = {Microbial epidemiology and population genomics have previously been carried out near-exclusively for organisms grown in vitro. Metagenomics helps to overcome this limitation, but it is still challenging to achieve strain-level characterization of microorganisms from culture-independent data with sufficient resolution for epidemiological modelling. Here, we have developed multiple complementary approaches that can be combined to profile and track individual microbial strains. To specifically profile highly recombinant neisseriae from oral metagenomes, we integrated four metagenomic analysis techniques: single nucleotide polymorphisms in the clade's core genome, DNA uptake sequence signatures, metagenomic multilocus sequence typing and strain-specific marker genes. We applied these tools to 520 oral metagenomes from the Human Microbiome Project, finding evidence of site tropism and temporal intra-subject strain retention. Although the opportunistic pathogen Neisseria meningitidis is enriched for colonization in the throat, N. flavescens and N. subflava populate the tongue dorsum, and N. sicca, N. mucosa and N. elongata the gingival plaque. The buccal mucosa appeared as an intermediate ecological niche between the plaque and the tongue. The resulting approaches to metagenomic strain profiling are generalizable and can be extended to other organisms and microbiomes across environments.}, }
@article {pmid27571759, year = {2016}, author = {Stulberg, E and Fravel, D and Proctor, LM and Murray, DM and LoTempio, J and Chrisey, L and Garland, J and Goodwin, K and Graber, J and Harris, MC and Jackson, S and Mishkind, M and Porterfield, DM and Records, A}, title = {An assessment of US microbiome research.}, journal = {Nature microbiology}, volume = {1}, number = {}, pages = {15015}, pmid = {27571759}, issn = {2058-5276}, mesh = {Biomedical Research/methods/*trends ; *Biota ; Capital Financing ; Computational Biology/methods ; Humans ; Metagenomics/methods ; Microbiological Techniques/standards ; Microbiology/*trends ; United States ; }, abstract = {Genome-enabled technologies have supported a dramatic increase in our ability to study microbial communities in environments and hosts. Taking stock of previously funded microbiome research can help to identify common themes, under-represented areas and research priorities to consider moving forward. To assess the status of US microbiome research, a team of government scientists conducted an analysis of federally funded microbiome research. Microbiomes were defined as host-, ecosystem- or habitat-associated communities of microorganisms, and microbiome research was defined as those studies that emphasize community-level analyses using 'omics technologies. Single pathogen, single strain and culture-based studies were not included, except symbiosis studies that served as models for more complex communities. Fourteen governmental organizations participated in the data call. The analysis examined three broad research themes, eight environments and eight microbial categories. Human microbiome research was larger than any other environment studied, and the basic biology research theme accounted for half of the total research activities. Computational biology and bioinformatics, reference databases and biorepositories, standardized protocols and high-throughput tools were commonly identified needs. Longitudinal and functional studies and interdisciplinary research were also identified as needs. This study has implications for the funding of future microbiome research, not only in the United States but beyond.}, }
@article {pmid27571098, year = {2016}, author = {Collins, S and Reid, G}, title = {Distant Site Effects of Ingested Prebiotics.}, journal = {Nutrients}, volume = {8}, number = {9}, pages = {}, pmid = {27571098}, issn = {2072-6643}, mesh = {Animals ; Bacteria/classification/*metabolism ; Bone Density ; Bone Remodeling ; Cognition ; *Fermentation ; *Gastrointestinal Microbiome ; Gastrointestinal Tract/*microbiology ; Host-Pathogen Interactions ; Humans ; Immune System/metabolism/physiopathology ; Lipids/blood ; Nervous System/metabolism/physiopathology ; Prebiotics/*administration &amp; dosage ; Skin/metabolism/physiopathology ; }, abstract = {The gut microbiome is being more widely recognized for its association with positive health outcomes, including those distant to the gastrointestinal system. This has given the ability to maintain and restore microbial homeostasis a new significance. Prebiotic compounds are appealing for this purpose as they are generally food-grade substances only degraded by microbes, such as bifidobacteria and lactobacilli, from which beneficial short-chain fatty acids are produced. Saccharides such as inulin and other fructo-oligosaccharides, galactooligosaccharides, and polydextrose have been widely used to improve gastrointestinal outcomes, but they appear to also influence distant sites. This review examined the effects of prebiotics on bone strength, neural and cognitive processes, immune functioning, skin, and serum lipid profile. The mode of action is in part affected by intestinal permeability and by fermentation products reaching target cells. As the types of prebiotics available diversify, so too will our understanding of the range of microbes able to degrade them, and the extent to which body sites can be impacted by their consumption.}, }
@article {pmid27562819, year = {2016}, author = {Herreros Martínez, B}, title = {Gastric microbiota and carcinogenesis - Current evidence and controversy.}, journal = {Revista espanola de enfermedades digestivas}, volume = {108}, number = {9}, pages = {527-529}, doi = {10.17235/reed.2016.4559/2016}, pmid = {27562819}, issn = {1130-0108}, mesh = {*Bacteria ; Carcinogenesis ; Dysbiosis ; Humans ; Microbiota ; *Stomach ; }, abstract = {Growing research on the human microbiome, even beyond the gastrointestinal area, is not surprising mainly due to significant advances in study methods. Current reporting in this area is so intensive that clinicians are changing the unsuitable "bacterial flora" expression for more appropriate terms such as "microbiota" (the entire microbial community colonizing an ecologic niche), "microbiome" (their collective genome), or "dysbiosis" (microbial composition imbalance with respect to the normatively considered pattern). Since the diseases involved in the altered microbiota hypothesis are increasing, its implication for cancer should come as no surprise to us.}, }
@article {pmid27558918, year = {2016}, author = {Anderson, EL and Li, W and Klitgord, N and Highlander, SK and Dayrit, M and Seguritan, V and Yooseph, S and Biggs, W and Venter, JC and Nelson, KE and Jones, MB}, title = {A robust ambient temperature collection and stabilization strategy: Enabling worldwide functional studies of the human microbiome.}, journal = {Scientific reports}, volume = {6}, number = {}, pages = {31731}, pmid = {27558918}, issn = {2045-2322}, mesh = {Algorithms ; Cohort Studies ; DNA, Bacterial/analysis/chemistry ; Feces ; Freezing ; Humans ; Linear Models ; *Microbiota ; Models, Statistical ; Nucleic Acids/chemistry ; Open Reading Frames ; Quality Control ; Reproducibility of Results ; Specimen Handling/*methods ; *Temperature ; Whole Genome Sequencing ; }, abstract = {As reports on possible associations between microbes and the host increase in number, more meaningful interpretations of this information require an ability to compare data sets across studies. This is dependent upon standardization of workflows to ensure comparability both within and between studies. Here we propose the standard use of an alternate collection and stabilization method that would facilitate such comparisons. The DNA Genotek OMNIgene∙Gut Stool Microbiome Kit was compared to the currently accepted community standard of freezing to store human stool samples prior to whole genome sequencing (WGS) for microbiome studies. This stabilization and collection device allows for ambient temperature storage, automation, and ease of shipping/transfer of samples. The device permitted the same data reproducibility as with frozen samples, and yielded higher recovery of nucleic acids. Collection and stabilization of stool microbiome samples with the DNA Genotek collection device, combined with our extraction and WGS, provides a robust, reproducible workflow that enables standardized global collection, storage, and analysis of stool for microbiome studies.}, }
@article {pmid27555308, year = {2016}, author = {Sze, MA and Schloss, PD}, title = {Looking for a Signal in the Noise: Revisiting Obesity and the Microbiome.}, journal = {mBio}, volume = {7}, number = {4}, pages = {}, pmid = {27555308}, issn = {2150-7511}, support = {P30 DK034933/DK/NIDDK NIH HHS/United States ; R25 GM116149/GM/NIGMS NIH HHS/United States ; }, mesh = {Biostatistics ; *Gastrointestinal Microbiome ; Humans ; *Microbiota ; *Obesity ; }, abstract = {UNLABELLED: Two recent studies have reanalyzed previously published data and found that when data sets were analyzed independently, there was limited support for the widely accepted hypothesis that changes in the microbiome are associated with obesity. This hypothesis was reconsidered by increasing the number of data sets and pooling the results across the individual data sets. The preferred reporting items for systematic reviews and meta-analyses guidelines were used to identify 10 studies for an updated and more synthetic analysis. Alpha diversity metrics and the relative risk of obesity based on those metrics were used to identify a limited number of significant associations with obesity; however, when the results of the studies were pooled by using a random-effect model, significant associations were observed among Shannon diversity, the number of observed operational taxonomic units, Shannon evenness, and obesity status. They were not observed for the ratio of Bacteroidetes and Firmicutes or their individual relative abundances. Although these tests yielded small P values, the difference between the Shannon diversity indices of nonobese and obese individuals was 2.07%. A power analysis demonstrated that only one of the studies had sufficient power to detect a 5% difference in diversity. When random forest machine learning models were trained on one data set and then tested by using the other nine data sets, the median accuracy varied between 33.01 and 64.77% (median, 56.68%). Although there was support for a relationship between the microbial communities found in human feces and obesity status, this association was relatively weak and its detection is confounded by large interpersonal variation and insufficient sample sizes.<br><br>IMPORTANCE: As interest in the human microbiome grows, there is an increasing number of studies that can be used to test numerous hypotheses across human populations. The hypothesis that variation in the gut microbiota can explain or be used to predict obesity status has received considerable attention and is frequently mentioned as an example of the role of the microbiome in human health. Here we assessed this hypothesis by using 10 independent studies and found that although there is an association, it is smaller than can be detected by most microbiome studies. Furthermore, we directly tested the ability to predict obesity status on the basis of the composition of an individual's microbiome and found that the median classification accuracy is between 33.01 and 64.77%. This type of analysis can be used to design future studies and expanded to explore other hypotheses.}, }
@article {pmid27545210, year = {2016}, author = {Ramadan, M and Solyman, S and Taha, M and Hanora, A}, title = {Preliminary characterization of human skin microbiome in healthy Egyptian individuals.}, journal = {Cellular and molecular biology (Noisy-le-Grand, France)}, volume = {62}, number = {8}, pages = {21-27}, pmid = {27545210}, issn = {1165-158X}, mesh = {Bacteria/genetics ; Biodiversity ; Cluster Analysis ; Egypt ; *Health ; Humans ; Microbiota/*genetics ; Phylogeny ; Principal Component Analysis ; Sequence Analysis, DNA ; Skin/*microbiology ; Species Specificity ; }, abstract = {Human skin is a large, complex ecosystem that harbors diverse microbial communities. The rapid advances in molecular techniques facilitate the exploration of skin associated bacterial populations. The objective of this study was to perform a preliminary characterization of skin associated bacterial populations in Egyptian individuals. Samples were collected from five healthy subjects from two skin sites; Antecubital Fossa (AF) and Popliteal Fossa (PF). Genomic DNA was extracted and used to amplify bacterial 16S rRNA genes which were sequenced on Illumina MiSeq platform. The two sites showed distinct diversity where PF was more diverse than AF. Taxonomic analysis of sequences revealed four main phyla Proteobacteria, Firmicutes, Actinobacteria and Deinococcus-Thermus, with Proteobacteria presenting the highest diversity. Klebsiella, Bacillus, Pseudomonas and Escherichia were the most predominant genera. Our data suggest that environmental factors can shape the composition of the skin microbiome in certain geographical regions. This study presents a new insight for subsequent analyses of human microbiome in Egypt.}, }
@article {pmid27542133, year = {2016}, author = {Vaughn, BP and Vatanen, T and Allegretti, JR and Bai, A and Xavier, RJ and Korzenik, J and Gevers, D and Ting, A and Robson, SC and Moss, AC}, title = {Increased Intestinal Microbial Diversity Following Fecal Microbiota Transplant for Active Crohn's Disease.}, journal = {Inflammatory bowel diseases}, volume = {22}, number = {9}, pages = {2182-2190}, pmid = {27542133}, issn = {1536-4844}, support = {K23 DK084338/DK/NIDDK NIH HHS/United States ; R03 DK105161/DK/NIDDK NIH HHS/United States ; T32 DK007760/DK/NIDDK NIH HHS/United States ; }, mesh = {Adult ; Crohn Disease/*microbiology/*therapy ; Donor Selection ; Dysbiosis/*therapy ; *Fecal Microbiota Transplantation ; Feces/microbiology ; Female ; *Gastrointestinal Microbiome ; Humans ; Intestinal Mucosa/immunology ; Intestines/microbiology ; Male ; Metabolic Networks and Pathways ; Middle Aged ; Prospective Studies ; Remission Induction ; T-Lymphocytes/classification ; United States ; Whole Genome Sequencing ; Young Adult ; }, abstract = {BACKGROUND: The microbiota in the lumen of patients with Crohn's disease (CD) is characterized by reduced diversity, particularly Firmicutes and Bacteroidetes. It is unknown whether the introduction of the intestinal microbiota from healthy individuals could correct this dysbiosis and reverse mucosal inflammation. We investigated the response to fecal microbial transplantation (FMT) from healthy individuals to subjects with active CD.<br><br>METHODS: We performed a prospective open-label study (uncontrolled) of FMT from healthy donors to subjects with active CD. A single FMT was performed by colonoscopy. Recipients' microbial diversity, mucosal T-cell phenotypes, and clinical and inflammatory parameters were measured over 12 weeks, and safety over 26 weeks.<br><br>RESULTS: Nineteen subjects were treated with FMT and completed the study follow-up. Fifty-eight percent (11/19) demonstrated a clinical response (Harvey-Bradshaw Index decrease >3) following FMT. Fifteen subjects had sufficient pre/postfecal samples for analysis. A significant increase in microbial diversity occurred after FMT (P = 0.02). This was greater in clinical responders than nonresponders. Patients who experienced a clinical response demonstrated a significant shift in fecal microbial composition toward their donor's profile as assessed by the Bray-Curtis index at 4 weeks (P = 0.003). An increase in regulatory T cells (CD4CD25CD127lo) was also noted in recipients' lamina propria following FMT. No serious adverse events were noted over the 26-week study period.<br><br>CONCLUSIONS: In this open-label study, FMT led to an expansion in microbial bacterial diversity in patients with active CD. FMT was overall safe, although the clinical response was variable. Determining donor microbial factors that influence clinical response is needed before randomized clinical trials of FMT in CD.}, }
@article {pmid27527985, year = {2016}, author = {Li, L and Ma, ZS}, title = {Testing the Neutral Theory of Biodiversity with Human Microbiome Datasets.}, journal = {Scientific reports}, volume = {6}, number = {}, pages = {31448}, pmid = {27527985}, issn = {2045-2322}, mesh = {Bacteria/*classification ; *Biota ; Humans ; *Microbiota ; Models, Biological ; }, abstract = {The human microbiome project (HMP) has made it possible to test important ecological theories for arguably the most important ecosystem to human health-the human microbiome. Existing limited number of studies have reported conflicting evidence in the case of the neutral theory; the present study aims to comprehensively test the neutral theory with extensive HMP datasets covering all five major body sites inhabited by the human microbiome. Utilizing 7437 datasets of bacterial community samples, we discovered that only 49 communities (less than 1%) satisfied the neutral theory, and concluded that human microbial communities are not neutral in general. The 49 positive cases, although only a tiny minority, do demonstrate the existence of neutral processes. We realize that the traditional doctrine of microbial biogeography "Everything is everywhere, but the environment selects" first proposed by Baas-Becking resolves the apparent contradiction. The first part of Baas-Becking doctrine states that microbes are not dispersal-limited and therefore are neutral prone, and the second part reiterates that the freely dispersed microbes must endure selection by the environment. Therefore, in most cases, it is the host environment that ultimately shapes the community assembly and tip the human microbiome to niche regime.}, }
@article {pmid27520820, year = {2016}, author = {Trinder, M and McDowell, TW and Daisley, BA and Ali, SN and Leong, HS and Sumarah, MW and Reid, G}, title = {Probiotic Lactobacillus rhamnosus Reduces Organophosphate Pesticide Absorption and Toxicity to Drosophila melanogaster.}, journal = {Applied and environmental microbiology}, volume = {82}, number = {20}, pages = {6204-6213}, pmid = {27520820}, issn = {1098-5336}, mesh = {Animals ; Caco-2 Cells ; Chlorpyrifos/metabolism/toxicity ; Drosophila melanogaster/*drug effects/*metabolism ; Female ; Humans ; Lacticaseibacillus rhamnosus/*metabolism ; Male ; Organophosphates/*metabolism/toxicity ; Pesticides/*metabolism/toxicity ; Probiotics/*pharmacology ; }, abstract = {UNLABELLED: Organophosphate pesticides used in agriculture can pose health risks to humans and wildlife. We hypothesized that dietary supplementation with Lactobacillus, a genus of commensal bacteria, would reduce absorption and toxicity of consumed organophosphate pesticides (parathion and chlorpyrifos [CP]). Several Lactobacillus species were screened for toleration of 100 ppm of CP or parathion in MRS broth based on 24-h growth curves. Certain Lactobacillus strains were unable to reach stationary-phase culture maxima and displayed an abnormal culture morphology in response to pesticide. Further characterization of commonly used, pesticide-tolerant and pesticide-susceptible, probiotic Lactobacillus rhamnosus strain GG (LGG) and L. rhamnosus strain GR-1 (LGR-1), respectively, revealed that both strains could significantly sequester organophosphate pesticides from solution after 24-h coincubations. This effect was independent of metabolic activity, as L. rhamnosus GG did not hydrolyze CP and no difference in organophosphate sequestration was observed between live and heat-killed strains. Furthermore, LGR-1 and LGG reduced the absorption of 100 μM parathion or CP in a Caco-2 Transwell model of the small intestine epithelium. To determine the effect of sequestration on acute toxicity, newly eclosed Drosophila melanogaster flies were exposed to food containing 10 μM CP with or without supplementation with live LGG. Supplementation with LGG simultaneously, but not with administration of CP 3 days prior (prophylactically), mitigated CP-induced mortality. In summary, the results suggest that L. rhamnosus may be useful for reducing toxic organophosphate pesticide exposure via passive binding. These findings could be transferable to clinical and livestock applications due to affordability and practical ability to supplement products with food-grade bacteria.<br><br>IMPORTANCE: The consequences of environmental pesticide pollution due to widespread usage in agriculture and soil leaching are becoming a major societal concern. Although the long-term effects of low-dose pesticide exposure for humans and wildlife remain largely unknown, logic suggests that these chemicals are not aligned with ecosystem health. This observation is most strongly supported by the agricultural losses associated with honeybee population declines, known as colony collapse disorder, in which pesticide usage is a likely trigger. Lactobacilli are bacteria used as beneficial microorganisms in fermented foods and have shown potentials to sequester and degrade environmental toxins. This study demonstrated that commonly used probiotic strains of lactobacilli could sequester, but not metabolize, organophosphate pesticides (parathion and chlorpyrifos). This Lactobacillus-mediated sequestration was associated with decreased intestinal absorption and insect toxicity in appropriate models. These findings hold promise for supplementing human, livestock, or apiary foods with probiotic microorganisms to reduce organophosphate pesticide exposure.}, }
@article {pmid27515741, year = {2016}, author = {Alekseyenko, AV}, title = {Multivariate Welch t-test on distances.}, journal = {Bioinformatics (Oxford, England)}, volume = {32}, number = {23}, pages = {3552-3558}, pmid = {27515741}, issn = {1367-4811}, mesh = {Animals ; Computer Simulation ; Gastrointestinal Tract/microbiology ; Humans ; Mice ; *Microbiota ; *Models, Statistical ; Psoriasis/microbiology ; Sample Size ; Skin/microbiology ; }, abstract = {MOTIVATION: Permutational non-Euclidean analysis of variance, PERMANOVA, is routinely used in exploratory analysis of multivariate datasets to draw conclusions about the significance of patterns visualized through dimension reduction. This method recognizes that pairwise distance matrix between observations is sufficient to compute within and between group sums of squares necessary to form the (pseudo) F statistic. Moreover, not only Euclidean, but arbitrary distances can be used. This method, however, suffers from loss of power and type I error inflation in the presence of heteroscedasticity and sample size imbalances.<br><br>RESULTS: We develop a solution in the form of a distance-based Welch t-test, [Formula: see text], for two sample potentially unbalanced and heteroscedastic data. We demonstrate empirically the desirable type I error and power characteristics of the new test. We compare the performance of PERMANOVA and [Formula: see text] in reanalysis of two existing microbiome datasets, where the methodology has originated.<br><br>The source code for methods and analysis of this article is available at https://github.com/alekseyenko/Tw2 Further guidance on application of these methods can be obtained from the author.<br><br>CONTACT: alekseye@musc.edu.}, }
@article {pmid27515213, year = {2016}, author = {Gominak, SC}, title = {Vitamin D deficiency changes the intestinal microbiome reducing B vitamin production in the gut. The resulting lack of pantothenic acid adversely affects the immune system, producing a "pro-inflammatory" state associated with atherosclerosis and autoimmunity.}, journal = {Medical hypotheses}, volume = {94}, number = {}, pages = {103-107}, doi = {10.1016/j.mehy.2016.07.007}, pmid = {27515213}, issn = {1532-2777}, mesh = {Acetylcholine/metabolism ; Arthritis/pathology ; Atherosclerosis ; Autoimmune Diseases ; Autoimmunity ; Body Weight ; *Gastrointestinal Microbiome ; Humans ; Hydrocortisone/metabolism ; Immune System ; Inflammation ; Intestinal Diseases/complications ; Intestinal Mucosa/*metabolism ; Intestines/microbiology ; Obesity/complications ; Pain ; Pantothenic Acid/*deficiency ; Seasons ; Sleep ; Sleep Wake Disorders/complications ; Vitamin B Complex/*biosynthesis/therapeutic use ; Vitamin D/therapeutic use ; Vitamin D Deficiency/*complications ; }, abstract = {STUDY OBJECTIVES: Vitamin D blood levels of 60-80ng/ml promote normal sleep. The present study was undertaken to explore why this beneficial effect waned after 2years as arthritic pain increased. Pantothenic acid becomes coenzyme A, a cofactor necessary for cortisol and acetylcholine production. 1950s experiments suggested a connection between pantothenic acid deficiency, autoimmune arthritis and insomnia. The B vitamins have been shown to have an intestinal bacterial source and a food source, suggesting that the normal intestinal microbiome may have always been the primary source of B vitamins. Review of the scientific literature shows that pantothenic acid does not have a natural food source, it is supplied by the normal intestinal bacteria. In order to test the hypothesis that vitamin D replacement slowly induced a secondary pantothenic acid deficiency, B100 (100mg of all B vitamins except 100mcg of B12 and biotin and 400mcg of folate) was added to vitamin D supplementation.<br><br>METHODS: Vitamin D and B100 were recommended to over 1000 neurology patients. Sleep characteristics, pain levels, neurologic symptoms, and bowel complaints were recorded by the author at routine appointments.<br><br>RESULTS: Three months of vitamin D plus B100 resulted in improved sleep, reduced pain and unexpected resolution of bowel symptoms. These results suggest that the combination of vitamin D plus B100 creates an intestinal environment that favors the return of the four specific species, Actinobacteria, Bacteroidetes, Firmicutes and Proteobacteria that make up the normal human microbiome.<br><br>HYPOTHESES: 1) Seasonal fluctuations in vitamin D levels have normally produced changes in the intestinal microbiome that promoted weight gain in winter. Years of vitamin D deficiency, however, results in a permanently altered intestinal environment that no longer favors the "healthy foursome". 2) Humans have always had a commensal relationship with their intestinal microbiome. We supplied them vitamin D, they supplied us B vitamins. 3) The four species that make up the normal microbiome are also commensal, each excretes at least one B vitamin that the other three need but cannot make. 4) Improved sleep and more cellular repairs eventually depletes body stores of pantothenic acid, causing reduced cortisol production, increased arthritic pain and widespread "pro-inflammatory" effects on the immune system. 5) Pantothenic acid deficiency also decreases available acetylcholine, the neurotransmitter used by the parasympathetic nervous system. Unopposed, increased sympathetic tone then produces hypertension, tachycardia, atrial arrhythmias and a "hyper-adrenergic" state known to predispose to heart disease and stroke.}, }
@article {pmid27513210, year = {2017}, author = {Noecker, C and McNally, CP and Eng, A and Borenstein, E}, title = {High-resolution characterization of the human microbiome.}, journal = {Translational research : the journal of laboratory and clinical medicine}, volume = {179}, number = {}, pages = {7-23}, pmid = {27513210}, issn = {1878-1810}, support = {DP2 AT007802/AT/NCCIH NIH HHS/United States ; T32 HG000035/HG/NHGRI NIH HHS/United States ; }, mesh = {Humans ; Metagenome/genetics ; Metagenomics ; Microbiota/*genetics ; Molecular Sequence Annotation ; RNA, Ribosomal, 16S/genetics ; }, abstract = {The human microbiome plays an important and increasingly recognized role in human health. Studies of the microbiome typically use targeted sequencing of the 16S rRNA gene, whole metagenome shotgun sequencing, or other meta-omic technologies to characterize the microbiome's composition, activity, and dynamics. Processing, analyzing, and interpreting these data involve numerous computational tools that aim to filter, cluster, annotate, and quantify the obtained data and ultimately provide an accurate and interpretable profile of the microbiome's taxonomy, functional capacity, and behavior. These tools, however, are often limited in resolution and accuracy and may fail to capture many biologically and clinically relevant microbiome features, such as strain-level variation or nuanced functional response to perturbation. Over the past few years, extensive efforts have been invested toward addressing these challenges and developing novel computational methods for accurate and high-resolution characterization of microbiome data. These methods aim to quantify strain-level composition and variation, detect and characterize rare microbiome species, link specific genes to individual taxa, and more accurately characterize the functional capacity and dynamics of the microbiome. These methods and the ability to produce detailed and precise microbiome information are clearly essential for informing microbiome-based personalized therapies. In this review, we survey these methods, highlighting the challenges each method sets out to address and briefly describing methodological approaches.}, }
@article {pmid27512653, year = {2016}, author = {Karstens, L and Asquith, M and Davin, S and Stauffer, P and Fair, D and Gregory, WT and Rosenbaum, JT and McWeeney, SK and Nardos, R}, title = {Does the Urinary Microbiome Play a Role in Urgency Urinary Incontinence and Its Severity?.}, journal = {Frontiers in cellular and infection microbiology}, volume = {6}, number = {}, pages = {78}, pmid = {27512653}, issn = {2235-2988}, support = {K12 HD043488/HD/NICHD NIH HHS/United States ; UL1 TR000128/TR/NCATS NIH HHS/United States ; }, mesh = {Adult ; Aged ; Bacteria/classification/genetics/*isolation &amp; purification ; Base Sequence ; Biodiversity ; Case-Control Studies ; DNA, Bacterial/genetics ; Female ; Humans ; Microbiota/genetics/*physiology ; Middle Aged ; Phylogeny ; Pilot Projects ; Prospective Studies ; Severity of Illness Index ; Urinary Bladder Diseases/microbiology/urine ; Urinary Incontinence/*microbiology/physiopathology/urine ; Urinary Tract/microbiology ; }, abstract = {OBJECTIVES: Traditionally, the urinary tract has been thought to be sterile in the absence of a clinically identifiable infection. However, recent evidence suggests that the urinary tract harbors a variety of bacterial species, known collectively as the urinary microbiome, even when clinical cultures are negative. Whether these bacteria promote urinary health or contribute to urinary tract disease remains unknown. Emerging evidence indicates that a shift in the urinary microbiome may play an important role in urgency urinary incontinence (UUI). The goal of this prospective pilot study was to determine how the urinary microbiome is different between women with and without UUI. We also sought to identify if characteristics of the urinary microbiome are associated with UUI severity.<br><br>METHODS: We collected urine from clinically well-characterized women with UUI (n = 10) and normal bladder function (n = 10) using a transurethral catheter to avoid bacterial contamination from external tissue. To characterize the resident microbial community, we amplified the bacterial 16S rRNA gene by PCR and performed sequencing using Illumina MiSeq. Sequences were processed using the workflow package QIIME. We identified bacteria that had differential relative abundance between UUI and controls using DESeq2 to fit generalized linear models based on the negative binomial distribution. We also identified relationships between the diversity of the urinary microbiome and severity of UUI symptoms with Pearson's correlation coefficient.<br><br>RESULTS: We successfully extracted and sequenced bacterial DNA from 95% of the urine samples and identified that there is a polymicrobial community in the female bladder in both healthy controls and women with UUI. We found the relative abundance of 14 bacteria significantly differed between control and UUI samples. Furthermore, we established that an increase in UUI symptom severity is associated with a decrease in microbial diversity in women with UUI.<br><br>CONCLUSIONS: Our study provides further characterization of the urinary microbiome in both healthy controls and extensively phenotyped women with UUI. Our results also suggest that the urinary microbiome may play an important role in the pathophysiology of UUI and that the loss of microbial diversity may be associated with clinical severity.}, }
@article {pmid27507964, year = {2016}, author = {Vernocchi, P and Del Chierico, F and Putignani, L}, title = {Gut Microbiota Profiling: Metabolomics Based Approach to Unravel Compounds Affecting Human Health.}, journal = {Frontiers in microbiology}, volume = {7}, number = {}, pages = {1144}, pmid = {27507964}, issn = {1664-302X}, abstract = {The gut microbiota is composed of a huge number of different bacteria, that produce a large amount of compounds playing a key role in microbe selection and in the construction of a metabolic signaling network. The microbial activities are affected by environmental stimuli leading to the generation of a wide number of compounds, that influence the host metabolome and human health. Indeed, metabolite profiles related to the gut microbiota can offer deep insights on the impact of lifestyle and dietary factors on chronic and acute diseases. Metagenomics, metaproteomics and metabolomics are some of the meta-omics approaches to study the modulation of the gut microbiota. Metabolomic research applied to biofluids allows to: define the metabolic profile; identify and quantify classes and compounds of interest; characterize small molecules produced by intestinal microbes; and define the biochemical pathways of metabolites. Mass spectrometry and nuclear magnetic resonance spectroscopy are the principal technologies applied to metabolomics in terms of coverage, sensitivity and quantification. Moreover, the use of biostatistics and mathematical approaches coupled with metabolomics play a key role in the extraction of biologically meaningful information from wide datasets. Metabolomic studies in gut microbiota-related research have increased, focusing on the generation of novel biomarkers, which could lead to the development of mechanistic hypotheses potentially applicable to the development of nutritional and personalized therapies.}, }
@article {pmid27507098, year = {2016}, author = {Schnorr, SL and Sankaranarayanan, K and Lewis, CM and Warinner, C}, title = {Insights into human evolution from ancient and contemporary microbiome studies.}, journal = {Current opinion in genetics &amp; development}, volume = {41}, number = {}, pages = {14-26}, pmid = {27507098}, issn = {1879-0380}, support = {R01 GM089886/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; *Ecology ; *Evolution, Molecular ; Humans ; Microbiota/*genetics ; Primates/genetics/*microbiology ; }, abstract = {Over the past decade, human microbiome research has energized the study of human evolution through a complete shift in our understanding of what it means to be human. The microbiome plays a pivotal role in human biology, performing key functions in digestion, mood and behavior, development and immunity, and a range of acute and chronic diseases. It is therefore critical to understand its evolution and changing ecology through time. Here we review recent findings on the microbiota of diverse human populations, non-human primates, and past human populations and discuss the implications of this research in formulating a deeper evolutionary understanding of the human holobiont.}, }
@article {pmid27494232, year = {2016}, author = {Reid, G}, title = {Can breast microbiota provide protective effects against cancer?.}, journal = {Future microbiology}, volume = {11}, number = {}, pages = {987-989}, doi = {10.2217/fmb-2016-0138}, pmid = {27494232}, issn = {1746-0921}, mesh = {Breast/*microbiology ; Breast Neoplasms/*prevention &amp; control ; Female ; Humans ; Lactation ; Lactobacillaceae/growth &amp; development/isolation &amp; purification/*physiology ; *Microbiota ; Milk, Human/microbiology ; Probiotics/therapeutic use ; }, }
@article {pmid27493014, year = {2016}, author = {Coit, P and Sawalha, AH}, title = {The human microbiome in rheumatic autoimmune diseases: A comprehensive review.}, journal = {Clinical immunology (Orlando, Fla.)}, volume = {170}, number = {}, pages = {70-79}, doi = {10.1016/j.clim.2016.07.026}, pmid = {27493014}, issn = {1521-7035}, mesh = {Autoimmune Diseases/*immunology/microbiology ; Bacteria/classification/genetics/immunology ; Dysbiosis/*immunology/microbiology ; Host-Pathogen Interactions/immunology ; Humans ; Microbiota/genetics/*immunology/physiology ; Population Dynamics ; RNA, Ribosomal, 16S/genetics ; Rheumatic Diseases/*immunology/microbiology ; Sequence Analysis, DNA ; }, abstract = {The human microbiome consists of the total diversity of microbiota and their genes. High-throughput sequencing has allowed for inexpensive and rapid evaluation of taxonomic representation and functional capability of the microbiomes of human body sites. Autoimmune and inflammatory rheumatic diseases are characterized by dysbiosis of the microbiome. Microbiome dysbiosis can be influenced by host genetics and environmental factors. Dysbiosis is also associated with shifts in certain functional pathways. The goal of this article is to provide a current and comprehensive review of the unique characteristics of the microbiome of patients with autoimmune and inflammatory rheumatic diseases, measured using high-throughput sequencing. We also highlight the need for broader studies utilizing a longitudinal approach to better understand how the human microbiome contributes to disease susceptibility, and to characterize the role of the interaction between host genetics and microbial diversity in the pathogenesis of autoimmune diseases, disease manifestations, and progression.}, }
@article {pmid27479330, year = {2016}, author = {Xu, L and Brito, IL and Alm, EJ and Blainey, PC}, title = {Virtual microfluidics for digital quantification and single-cell sequencing.}, journal = {Nature methods}, volume = {13}, number = {9}, pages = {759-762}, pmid = {27479330}, issn = {1548-7105}, support = {P30 ES002109/ES/NIEHS NIH HHS/United States ; U54 HG003067/HG/NHGRI NIH HHS/United States ; }, mesh = {DNA Contamination ; Electronic Data Processing ; Escherichia coli/genetics ; *Genome, Bacterial ; High-Throughput Nucleotide Sequencing/*methods ; Hydrogels/chemistry ; Microfluidics/*methods ; Microscopy, Fluorescence ; Nucleic Acid Amplification Techniques/*methods ; Sequence Analysis, DNA/*methods ; Single-Cell Analysis/*methods ; Staphylococcus aureus/genetics ; User-Computer Interface ; Workflow ; }, abstract = {We have developed hydrogel-based virtual microfluidics as a simple and robust alternative to complex engineered microfluidic systems for the compartmentalization of nucleic acid amplification reactions. We applied in-gel digital multiple displacement amplification (dMDA) to purified DNA templates, cultured bacterial cells and human microbiome samples in the virtual microfluidics system, and demonstrated whole-genome sequencing of single-cell MDA products with excellent coverage uniformity and markedly reduced chimerism compared with products of liquid MDA reactions.}, }
@article {pmid27474685, year = {2017}, author = {Wolf-Meyer, MJ}, title = {Normal, Regular, and Standard: Scaling the Body through Fecal Microbial Transplants.}, journal = {Medical anthropology quarterly}, volume = {31}, number = {3}, pages = {297-314}, doi = {10.1111/maq.12328}, pmid = {27474685}, issn = {0745-5194}, mesh = {Anthropology, Medical ; *Clostridioides difficile ; *Enterocolitis, Pseudomembranous/ethnology/microbiology/therapy ; *Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; United States/ethnology ; }, abstract = {In 2013, the National Institutes of Health (NIH) and the Food and Drug Administration (FDA) held a workshop to determine the risks and benefits associated with the experimental use of fecal microbial transplants to treat Clostridium difficile and other gastroenterological disorders. By focusing on the proceedings of the NIH-FDA workshop on the treatment of the human microbiome, the question of how medicine colonizes human bodies through microbial transplants raises questions about what an individual body is, how determinative of human health the microbiome is, and what the limits of molecular biomedicine are when the microbiome is taken into consideration. In the workshop presentations and discussion of this emerging treatment, experts used ideas about the normal, regular, and standard to move between scales of bodily analysis, from the microbial to the body politic, demonstrating how the individual and society are deeply influenced by the unruly community of microbial symbiotes that humans host.}, }
@article {pmid27454385, year = {2016}, author = {Yeh, A and Rogers, MB and Firek, B and Neal, MD and Zuckerbraun, BS and Morowitz, MJ}, title = {Dysbiosis Across Multiple Body Sites in Critically Ill Adult Surgical Patients.}, journal = {Shock (Augusta, Ga.)}, volume = {46}, number = {6}, pages = {649-654}, doi = {10.1097/SHK.0000000000000691}, pmid = {27454385}, issn = {1540-0514}, mesh = {Adult ; Corynebacterium/genetics/isolation &amp; purification ; *Critical Illness ; Dysbiosis/*genetics ; Enterococcus/genetics/isolation &amp; purification ; Faecalibacterium/genetics/isolation &amp; purification ; Feces/microbiology ; Humans ; Intensive Care Units/statistics &amp; numerical data ; Microbiota/genetics ; Mycoplasma/genetics/isolation &amp; purification ; Polymerase Chain Reaction ; RNA, Ribosomal, 16S/genetics ; Skin/microbiology ; Staphylococcus/genetics/isolation &amp; purification ; Tongue/microbiology ; }, abstract = {The microbiota of critically ill patients likely undergoes dramatic changes but has not been rigorously studied with a culture-independent high-throughput approach. The aim of this study was to characterize spatial and temporal variation in the microbiota of critically ill patients. Trauma and acute surgery patients admitted to the intensive care unit (ICU) were sampled at five body sites (stool, tongue, skin, trachea, urine) every 3 to 4 days. A mean of 10.8 samples was collected from 32 patients with a mean sampling period of 8.8 days. Bacterial 16S rRNA sequences were amplified and sequenced for microbiota analyses. Results were compared to data from unhospitalized adult participants in the American Gut and Human Microbiome Projects. Relative to healthy adults, alpha diversity was decreased in ICU gut and skin samples at all time points. Diversity in tongue swabs decreased over time. Beta diversity measures indicated differences in community membership between critically ill and healthy adults at each body site. Taxonomic alterations in the ICU included depletion of important commensal bacteria such as Faecalibacterium in GI samples and Corynebacterium in skin swabs and enrichment with pathogens such as Enterococcus, Mycoplasma, and Staphylococcus. A high proportion of ICU sample sets contained pathogens present simultaneously at three body sites indicating widespread colonization. In several cases, clinically relevant airway infections were preceded by the appearance of the causative pathogen in tracheal microbiome profiles. These results demonstrate that the microbiome of critically ill patients undergoes a loss of diversity, loss of site specificity, and a shift toward dominant pathogens. These changes may provide opportunities to precisely modulate the microbiome and thereby improve patient outcomes.}, }
@article {pmid27430014, year = {2016}, author = {Singh, RK and Wheildon, N and Ishikawa, S}, title = {Food Additive P-80 Impacts Mouse Gut Microbiota Promoting Intestinal Inflammation, Obesity and Liver Dysfunction.}, journal = {SOJ microbiology &amp; infectious diseases}, volume = {4}, number = {1}, pages = {}, pmid = {27430014}, issn = {2372-0956}, support = {/HHMI_/Howard Hughes Medical Institute/United States ; }, abstract = {The increasing prevalence of obesity has emerged as one of the most important global public health issue. The change to the human microbiome as a result of changes in the quality and quantity of food intake over the past several decades has been implicated in the development of obesity and metabolic syndrome. We administered polysorbate-80 to mice via gavage. The researchers monitor liver noninvasively using a bioluminescence imaging. For the liver dysfunction we measure the liver enzymes and PAS stain on liver, electron microscopy liver mitochondria. For the assessment of intestinal inflammation we measured fecal LCN2, LPS, MPO and flagellin by ELISA and qPCR. We use confocal microscopy to detect closet bacteria near the epithelium. 16S sequence was used for the composition of microbiota. Compared with control mice, those receiving emulsifier, showed impaired glycemic tolerance, hyperinsulinemia, altered liver enzymes, larger mitochondria and increased gall bladder size. Additionally, mice in the experimental group showed higher levels of DCA, reduced Muc2 RNA expression, reduced mucus thickness in the intestinal epithelium and increased gut permeability. Intestinal bacteria of mice receiving P-80 were found deeper in the mucus and closer to the intestinal epithelium and had increased level of bioactive LPS, flagellin and LCN2 expression. The result of the study are supportive of evidence that emulsifier agents such as polysorbate-80, may be contributing to obesity related intestinal inflammation and progression of liver dysfunction and alternation of gut microbiota.}, }
@article {pmid27429480, year = {2016}, author = {Maxson, T and Mitchell, DA}, title = {Targeted Treatment for Bacterial Infections: Prospects for Pathogen-Specific Antibiotics Coupled with Rapid Diagnostics.}, journal = {Tetrahedron}, volume = {72}, number = {25}, pages = {3609-3624}, pmid = {27429480}, issn = {0040-4020}, support = {DP2 OD008463/OD/NIH HHS/United States ; }, abstract = {Antibiotics are a cornerstone of modern medicine and have significantly reduced the burden of infectious diseases. However, commonly used broad-spectrum antibiotics can cause major collateral damage to the human microbiome, causing complications ranging from antibiotic-associated colitis to the rapid spread of resistance. Employing narrower spectrum antibiotics targeting specific pathogens may alleviate this predicament as well as provide additional tools to expand an antibiotic repertoire threatened by the inevitability of resistance. Improvements in clinical diagnosis will be required to effectively utilize pathogen-specific antibiotics and new molecular diagnostics are poised to fulfill this need. Here we review recent trends and the future prospects of deploying narrower spectrum antibiotics coupled with rapid diagnostics. Further, we discuss the theoretical advantages and limitations of this emerging approach to controlling bacterial infectious diseases.}, }
@article {pmid27409808, year = {2016}, author = {Brito, IL and Yilmaz, S and Huang, K and Xu, L and Jupiter, SD and Jenkins, AP and Naisilisili, W and Tamminen, M and Smillie, CS and Wortman, JR and Birren, BW and Xavier, RJ and Blainey, PC and Singh, AK and Gevers, D and Alm, EJ}, title = {Mobile genes in the human microbiome are structured from global to individual scales.}, journal = {Nature}, volume = {535}, number = {7612}, pages = {435-439}, pmid = {27409808}, issn = {1476-4687}, support = {U54 HG003067/HG/NHGRI NIH HHS/United States ; P30 DK043351/DK/NIDDK NIH HHS/United States ; U54HG003067/HG/NHGRI NIH HHS/United States ; T32 GM087237/GM/NIGMS NIH HHS/United States ; R01 DE020891/DE/NIDCR NIH HHS/United States ; }, mesh = {Bacteriophages/genetics ; Cohort Studies ; DNA Transposable Elements/genetics ; Diet ; Fiji ; Gene Pool ; Gene Transfer, Horizontal/*genetics ; *Gene-Environment Interaction ; Genetic Variation/*genetics ; Humans ; *Metagenomics ; Microbiota/*genetics ; North America ; Plasmids/genetics ; Recombination, Genetic/genetics ; Selection, Genetic/*genetics ; Single-Cell Analysis ; }, abstract = {Recent work has underscored the importance of the microbiome in human health, and has largely attributed differences in phenotype to differences in the species present among individuals. However, mobile genes can confer profoundly different phenotypes on different strains of the same species. Little is known about the function and distribution of mobile genes in the human microbiome, and in particular whether the gene pool is globally homogenous or constrained by human population structure. Here, we investigate this question by comparing the mobile genes found in the microbiomes of 81 metropolitan North Americans with those of 172 agrarian Fiji islanders using a combination of single-cell genomics and metagenomics. We find large differences in mobile gene content between the Fijian and North American microbiomes, with functional variation that mirrors known dietary differences such as the excess of plant-based starch degradation genes found in Fijian individuals. Notably, we also observed differences between the mobile gene pools of neighbouring Fijian villages, even though microbiome composition across villages is similar. Finally, we observe high rates of recombination leading to individual-specific mobile elements, suggesting that the abundance of some genes may reflect environmental selection rather than dispersal limitation. Together, these data support the hypothesis that human activities and behaviours provide selective pressures that shape mobile gene pools, and that acquisition of mobile genes is important for colonizing specific human populations.}, }
@article {pmid27408733, year = {2016}, author = {Bessis, S and Ndongo, S and Lagier, JC and Fournier, PE and Raoult, D}, title = {"Emergencia timonensis," a new bacterium isolated from the stool of a healthy patient.}, journal = {New microbes and new infections}, volume = {12}, number = {}, pages = {73-75}, pmid = {27408733}, issn = {2052-2975}, abstract = {We present the essential characteristics of "Emergencia timonensis" strain SN18 (= CSUR P2260), a new member of the order Clostridiales that was isolated from the stool of healthy patient.}, }
@article {pmid27407273, year = {2016}, author = {Leszczyszyn, JJ and Radomski, M and Leszczyszyn, AM}, title = {Intestinal microbiota transplant - current state of knowledge.}, journal = {Reumatologia}, volume = {54}, number = {1}, pages = {24-28}, pmid = {27407273}, issn = {0034-6233}, abstract = {Faecal microbiota transplantation (FMT) has induced a lot scientific interest and hopes for the last couple of years. FMT has been approved as a treatment of recurrent Clostridium difficile colitis. Highly sophisticated molecular DNA identification methods have been used to assess the healthy human microbiome as well as its disturbances in several diseases. The metabolic and immunologic functions of the microbiome have become more clear and understandable. A lot of pathological changes, such as production of short-chain fatty acids or components of the inflammatory cascade, caused by changes in microbiome diversity, variability and richness have been observed among patients suffering from inflammatory bowel diseases, irritable bowel syndrome, type 2 diabetes or rheumatoid arthritis. The published clinical results are encouraging, but still there is huge demand for FMT controlled clinical trials.}, }
@article {pmid27397930, year = {2016}, author = {Peccia, J and Kwan, SE}, title = {Buildings, Beneficial Microbes, and Health.}, journal = {Trends in microbiology}, volume = {24}, number = {8}, pages = {595-597}, doi = {10.1016/j.tim.2016.04.007}, pmid = {27397930}, issn = {1878-4380}, mesh = {Aerosols ; *Air Pollution, Indoor ; Asthma/microbiology ; Bacteria/pathogenicity ; Bacterial Physiological Phenomena ; Environmental Health ; Environmental Microbiology ; Environmental Monitoring ; Fungi/pathogenicity ; Humans ; *Hygiene ; *Microbiota ; }, abstract = {Bacteria and fungi in buildings exert an influence on the human microbiome through aerosol deposition, surface contact, and human and animal interactions. As the identities and functions of beneficial human microbes emerge, the consequences of building design, operation, and function must be understood to maintain the health of occupants in buildings.}, }
@article {pmid27396567, year = {2016}, author = {Wang, J and Jia, H}, title = {Metagenome-wide association studies: fine-mining the microbiome.}, journal = {Nature reviews. Microbiology}, volume = {14}, number = {8}, pages = {508-522}, pmid = {27396567}, issn = {1740-1534}, mesh = {Arthritis, Rheumatoid/diagnosis/microbiology/prevention &amp; control ; Bacteria/*genetics ; Colorectal Neoplasms/diagnosis/microbiology/prevention &amp; control ; Diabetes Mellitus, Type 2/diagnosis/microbiology/prevention &amp; control ; Gastrointestinal Tract/microbiology ; *Genome-Wide Association Study ; High-Throughput Nucleotide Sequencing ; Humans ; Liver Cirrhosis/diagnosis/microbiology/prevention &amp; control ; *Metagenome ; *Microbiota ; Obesity/diagnosis/microbiology/prevention &amp; control ; RNA, Ribosomal, 16S/genetics ; ROC Curve ; }, abstract = {Metagenome-wide association studies (MWAS) have enabled the high-resolution investigation of associations between the human microbiome and several complex diseases, including type 2 diabetes, obesity, liver cirrhosis, colorectal cancer and rheumatoid arthritis. The associations that can be identified by MWAS are not limited to the identification of taxa that are more or less abundant, as is the case with taxonomic approaches, but additionally include the identification of microbial functions that are enriched or depleted. In this Review, we summarize recent findings from MWAS and discuss how these findings might inform the prevention, diagnosis and treatment of human disease in the future. Furthermore, we highlight the need to better characterize the biology of many of the bacteria that are found in the human microbiota as an essential step in understanding how bacterial strains that have been identified by MWAS are associated with disease.}, }
@article {pmid27380600, year = {2016}, author = {Putignani, L and Alisi, A and Nobili, V}, title = {Pediatric NAFLD: the Future role of Patient-Tailored Probiotics Therapy.}, journal = {Journal of pediatric gastroenterology and nutrition}, volume = {63 Suppl 1}, number = {}, pages = {S6-8}, doi = {10.1097/MPG.0000000000001220}, pmid = {27380600}, issn = {1536-4801}, mesh = {Child ; Evidence-Based Medicine ; Forecasting ; Humans ; Non-alcoholic Fatty Liver Disease/*therapy ; Probiotics/*therapeutic use ; }, abstract = {PURPOSE OF REVIEW: Clinical evidence of the use of probiotics in pediatric NAFLD, framed within gut microbiota response, is herein discussed.<br><br>RECENT FINDINGS: The assistance of a new microbiological approach in probiotics' design is playing a central role in NAFLD clinical management. Experimental studies demonstrated the effect of gut microbiota manipulation in NAFLD and recent clinical evidence reported their beneficial effect in pediatric patients.<br><br>SUMMARY: Epidemiology suggests that NAFLD is the most frequent pediatric chronic liver disease evolving from simple steatosis to a more severe form that may progress toward fibrosis. The goal of pharmacological treatment of NAFLD-related fibrosis is to stop and eventually to reverse liver damage, but no drug tested so far seem to be able to reach this endpoint. A few encouraging clinical studies demonstrated an improvement of hepato-metabolic milieu under probiotic treatment suggesting that they could exert an anti-fibrotic activity.Currently, new insights onto probiotics can be deduced by ad hoc generated NAFLD gut microbiota profiles. These functional maps may unveil gut ecosystem dynamics under probiotics' treatment, selecting the most appropriate for NAFLD gut microbiota amelioration.}, }
@article {pmid27375574, year = {2016}, author = {Nimkulrat, S and Lee, H and Doak, TG and Ye, Y}, title = {Genomic and Metagenomic Analysis of Diversity-Generating Retroelements Associated with Treponema denticola.}, journal = {Frontiers in microbiology}, volume = {7}, number = {}, pages = {852}, pmid = {27375574}, issn = {1664-302X}, abstract = {Diversity-generating retroelements (DGRs) are genetic cassettes that can produce massive protein sequence variation in prokaryotes. Presumably DGRs confer selective advantages to their hosts (bacteria or viruses) by generating variants of target genes-typically resulting in target proteins with altered ligand-binding specificity-through a specialized error-prone reverse transcription process. The only extensively studied DGR system is from the Bordetella phage BPP-1, although DGRs are predicted to exist in other species. Using bioinformatics analysis, we discovered that the DGR system associated with the Treponema denticola species (a human oral-associated periopathogen) is dynamic (with gains/losses of the system found in the isolates) and diverse (with multiple types found in isolated genomes and the human microbiota). The T. denticola DGR is found in only nine of the 17 sequenced T. denticola strains. Analysis of the DGR-associated template regions and reverse transcriptase gene sequences revealed two types of DGR systems in T. denticola: the ATCC35405-type shared by seven isolates including ATCC35405; and the SP32-type shared by two isolates (SP32 and SP33), suggesting multiple DGR acquisitions. We detected additional variants of the T. denticola DGR systems in the human microbiomes, and found that the SP32-type DGR is more abundant than the ATCC35405-type in the healthy human oral microbiome, although the latter is found in more sequenced isolates. This is the first comprehensive study to characterize the DGRs associated with T. denticola in individual genomes as well as human microbiomes, demonstrating the importance of utilizing both individual genomes and metagenomes for characterizing the elements, and for analyzing their diversity and distribution in human populations.}, }
@article {pmid27363992, year = {2016}, author = {Lau, JT and Whelan, FJ and Herath, I and Lee, CH and Collins, SM and Bercik, P and Surette, MG}, title = {Capturing the diversity of the human gut microbiota through culture-enriched molecular profiling.}, journal = {Genome medicine}, volume = {8}, number = {1}, pages = {72}, pmid = {27363992}, issn = {1756-994X}, mesh = {Aerobiosis ; Anaerobiosis ; Bacteria/classification/*genetics/isolation &amp; purification ; Biodiversity ; *Cell Culture Techniques ; Clostridiales/classification/*genetics/growth &amp; development/isolation &amp; purification ; Feces/microbiology ; Gastrointestinal Microbiome/*genetics ; Gastrointestinal Tract/microbiology ; *Genes, Bacterial ; Healthy Volunteers ; Humans ; Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; }, abstract = {BACKGROUND: The human gut microbiota has been implicated in most aspects of health and disease; however, most of the bacteria in this community are considered unculturable, so studies have relied on molecular-based methods. These methods generally do not permit the isolation of organisms, which is required to fully explore the functional roles of bacteria for definitive association with host phenotypes. Using a combination of culture and 16S rRNA gene sequencing, referred to as culture-enriched molecular profiling, we show that the majority of the bacteria identified by 16S sequencing of the human gut microbiota can be cultured.<br><br>METHODS: Five fresh, anaerobic fecal samples were cultured using 33 media and incubation of plates anaerobically and aerobically resulted in 66 culture conditions for culture-enriched molecular profiling. The cultivable portion of the fecal microbiota was determined by comparing the operational taxonomic units (OTUs) recovered by 16S sequencing of the culture plates to OTUs from culture-independent sequencing of the fecal sample. Targeted isolation of Lachnospiraceae strains using conditions defined by culture-enriched molecular profiling was carried out on two fresh stool samples.<br><br>RESULTS: We show that culture-enriched molecular profiling, utilizing 66 culture conditions combined with 16S rRNA gene sequencing, allowed for the culturing of an average of 95&#xa0;% of the OTUs present at greater than 0.1&#xa0;% abundance in fecal samples. Uncultured OTUs were low abundance in stool. Importantly, comparing culture-enrichment to culture-independent sequencing revealed that the majority of OTUs were detected only by culture, highlighting the advantage of culture for studying the diversity of the gut microbiota. Applying culture-enriched molecular profiling to target Lachnospiraceae strains resulted in the recovery of 79 isolates, 12 of which are on the Human Microbiome Project's "Most Wanted" list.<br><br>CONCLUSIONS: We show that, through culture-enriched molecular profiling, the majority of the bacteria in the human gut microbiota can be cultured and this method revealed greater bacterial diversity compared to culture-independent sequencing. Additionally, this method could be applied for the targeted recovery of a specific bacterial group. This approach allows for the isolation of bacteria of interest from the gut microbiota, providing new opportunities to explore mechanisms of microbiota-host interactions and the diversity of the human microbiota.}, }
@article {pmid27358350, year = {2016}, author = {Araos, R and Tai, AK and Snyder, GM and Blaser, MJ and D'Agata, EMC}, title = {Predominance of Lactobacillus spp. Among Patients Who Do Not Acquire Multidrug-Resistant Organisms.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {63}, number = {7}, pages = {937-943}, pmid = {27358350}, issn = {1537-6591}, support = {K24 AI119158/AI/NIAID NIH HHS/United States ; R01 DK090989/DK/NIDDK NIH HHS/United States ; }, mesh = {Anti-Bacterial Agents/pharmacology ; *Bacterial Infections/epidemiology/microbiology/prevention &amp; control ; *Cross Infection/epidemiology/microbiology/prevention &amp; control ; Drug Resistance, Multiple, Bacterial/*genetics ; Hospitalization/*statistics &amp; numerical data ; Humans ; Lactobacillus/*genetics/isolation &amp; purification ; Microbiota/drug effects/*genetics ; Prospective Studies ; Rectum/microbiology ; Risk Factors ; }, abstract = {BACKGROUND: The emergence and dissemination of multidrug-resistant organisms (MDROs) is a global threat. Characterizing the human microbiome among hospitalized patients and identifying unique microbial signatures among those patients who acquire MDROs may identify novel infection prevention strategies.<br><br>METHODS: Adult patients admitted to 5 general medical-surgical floors at a 649-bed, tertiary care center in Boston, Massachusetts, were classified according to in-hospital antimicrobial exposure and MDRO colonization status. Within 48 hours of hospital admission (baseline) and at discharge (follow-up), rectal swab samples were obtained, and compared with samples from an external control group of healthy persons from the community. DNA was extracted from samples, next-generation sequencing performed, and microbial community structure and taxonomic features assessed, comparing those who acquired MDROs and those who had not, and the external controls.<br><br>RESULTS: Hospitalized patients (n = 44) had reduced microbial diversity and a greater abundance of Escherichia spp. and Enterococcus spp. than healthy controls (n = 26). Among hospitalized patients, 25 had no MDROs at the time of the baseline sample and were also exposed to antimicrobials. Among this group, 7 (28%) acquired &#x2265;1 MDRO; demographic and clinical characteristics were similar between MDRO-acquisition and MDRO-nonacquisition groups. Patients in the nonacquisition group had consistently higher Lactobacillus spp. abundance than those in the acquisition group (linear discriminant score, 3.97; P = .04).<br><br>CONCLUSIONS: The fecal microbiota of the hospitalized subjects had abnormal community composition, and Lactobacillus spp. was associated with lack of MDRO acquisition, consistent with a protective role.}, }
@article {pmid27357925, year = {2016}, author = {Ozga, AT and Sankaranarayanan, K and Tito, RY and Obregon-Tito, AJ and Foster, MW and Tallbull, G and Spicer, P and Warinner, CG and Lewis, CM}, title = {Oral microbiome diversity among Cheyenne and Arapaho individuals from Oklahoma.}, journal = {American journal of physical anthropology}, volume = {161}, number = {2}, pages = {321-327}, doi = {10.1002/ajpa.23033}, pmid = {27357925}, issn = {1096-8644}, support = {R01 HG005172/HG/NHGRI NIH HHS/United States ; R01 GM089886/GM/NIGMS NIH HHS/United States ; }, mesh = {DNA, Bacterial/analysis/genetics ; Humans ; Indians, North American/*genetics ; Microbiota/*genetics ; Oklahoma ; Prevotella/genetics ; RNA, Ribosomal, 16S/genetics ; Saliva/*microbiology ; Sequence Analysis, DNA ; }, abstract = {OBJECTIVES: There is a major ascertainment bias in microbiome research, with individuals of predominately European ancestry living within metropolitan areas dominating most studies. Here we present a study of the salivary microbiome within a North American Indian community. This research is the culmination of four years of collaboration and community engagement with Cheyenne &amp; Arapaho (C&amp;A) tribal members from western Oklahoma.<br><br>MATERIALS AND METHODS: Using 16S rRNA gene amplification and next-generation sequencing, we generated microbial taxonomic inventories for 37 individuals representing five towns within the C&amp;A tribes. For comparison, we performed the same laboratory techniques on saliva samples from 20 non-native individuals (NNI) from Norman, Oklahoma.<br><br>RESULTS: The C&amp;A participants differ from the NNI in having reduced within-individual species richness and higher between-individual variation. Unsupervised clustering analyses reveal that three ecological groupings best fit the data, and while C&amp;A individuals include assignments to all three groups, the NNI individuals are assigned to only one group. One of the ecological groups found exclusively among C&amp;A participants was characterized by high abundance of the oral bacterial genus Prevotella.<br><br>DISCUSSION: The C&amp;A and NNI participants from Oklahoma have notable differences in their microbiome diversity, with a wider range of variation observed among the C&amp;A individuals, including a higher frequency of bacteria implicated in systemic disorders. Overall, this study highlights the importance of engagement with indigenous communities, and the need for an improved understanding of human microbiome diversity among underrepresented groups and those individuals living outside of metropolitan areas.}, }
@article {pmid27354505, year = {2016}, author = {Bloomfield, SF and Rook, GA and Scott, EA and Shanahan, F and Stanwell-Smith, R and Turner, P}, title = {Time to abandon the hygiene hypothesis: new perspectives on allergic disease, the human microbiome, infectious disease prevention and the role of targeted hygiene.}, journal = {Perspectives in public health}, volume = {136}, number = {4}, pages = {213-224}, pmid = {27354505}, issn = {1757-9147}, support = {MR/K010468/1/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Delphi Technique ; *Environmental Exposure ; Female ; Humans ; Hygiene ; *Hygiene Hypothesis ; *Hypersensitivity ; Male ; *Microbiota ; }, abstract = {AIMS: To review the burden of allergic and infectious diseases and the evidence for a link to microbial exposure, the human microbiome and immune system, and to assess whether we could develop lifestyles which reconnect us with exposures which could reduce the risk of allergic disease while also protecting against infectious disease.<br><br>METHODS: Using methodology based on the Delphi technique, six experts in infectious and allergic disease were surveyed to allow for elicitation of group judgement and consensus view on issues pertinent to the aim.<br><br>RESULTS: Key themes emerged where evidence shows that interaction with microbes that inhabit the natural environment and human microbiome plays an essential role in immune regulation. Changes in lifestyle and environmental exposure, rapid urbanisation, altered diet and antibiotic use have had profound effects on the human microbiome, leading to failure of immunotolerance and increased risk of allergic disease. Although evidence supports the concept of immune regulation driven by microbe-host interactions, the term 'hygiene hypothesis' is a misleading misnomer. There is no good evidence that hygiene, as the public understands, is responsible for the clinically relevant changes to microbial exposures.<br><br>CONCLUSION: Evidence suggests a combination of strategies, including natural childbirth, breast feeding, increased social exposure through sport, other outdoor activities, less time spent indoors, diet and appropriate antibiotic use, may help restore the microbiome and perhaps reduce risks of allergic disease. Preventive efforts must focus on early life. The term 'hygiene hypothesis' must be abandoned. Promotion of a risk assessment approach (targeted hygiene) provides a framework for maximising protection against pathogen exposure while allowing spread of essential microbes between family members. To build on these findings, we must change public, public health and professional perceptions about the microbiome and about hygiene. We need to restore public understanding of hygiene as a means to prevent infectious disease.}, }
@article {pmid27350143, year = {2016}, author = {Proctor, LM}, title = {The National Institutes of Health Human Microbiome Project.}, journal = {Seminars in fetal &amp; neonatal medicine}, volume = {21}, number = {6}, pages = {368-372}, doi = {10.1016/j.siny.2016.05.002}, pmid = {27350143}, issn = {1878-0946}, mesh = {Humans ; *Microbiota ; National Institutes of Health (U.S.) ; United States ; }, abstract = {This overview describes the impetus for and the goals of the National Institutes of Health (NIH)'s Human Microbiome Project (HMP) and the research resources available through the HMP. As the HMP also serves as a catalyst for human microbiome research at the NIH, NIH Institutes and Centers support for this field is also briefly addressed.}, }
@article {pmid27339941, year = {2016}, author = {Ma, Y and Hu, X and He, T and Jiang, X}, title = {Hessian regularization based symmetric nonnegative matrix factorization for clustering gene expression and microbiome data.}, journal = {Methods (San Diego, Calif.)}, volume = {111}, number = {}, pages = {80-84}, doi = {10.1016/j.ymeth.2016.06.017}, pmid = {27339941}, issn = {1095-9130}, mesh = {*Algorithms ; *Cluster Analysis ; Gene Expression/genetics ; Gene Expression Profiling/*methods/statistics &amp; numerical data ; Humans ; Microbiota/*genetics ; }, abstract = {Nonnegative matrix factorization (NMF) has received considerable attention due to its interpretation of observed samples as combinations of different components, and has been successfully used as a clustering method. As an extension of NMF, Symmetric NMF (SNMF) inherits the advantages of NMF. Unlike NMF, however, SNMF takes a nonnegative similarity matrix as an input, and two lower rank nonnegative matrices (H, H[T]) are computed as an output to approximate the original similarity matrix. Laplacian regularization has improved the clustering performance of NMF and SNMF. However, Laplacian regularization (LR), as a classic manifold regularization method, suffers some problems because of its weak extrapolating ability. In this paper, we propose a novel variant of SNMF, called Hessian regularization based symmetric nonnegative matrix factorization (HSNMF), for this purpose. In contrast to Laplacian regularization, Hessian regularization fits the data perfectly and extrapolates nicely to unseen data. We conduct extensive experiments on several datasets including text data, gene expression data and HMP (Human Microbiome Project) data. The results show that the proposed method outperforms other methods, which suggests the potential application of HSNMF in biological data clustering.}, }
@article {pmid27337482, year = {2016}, author = {Xavier, JB}, title = {Sociomicrobiology and Pathogenic Bacteria.}, journal = {Microbiology spectrum}, volume = {4}, number = {3}, pages = {}, pmid = {27337482}, issn = {2165-0497}, support = {DP2 OD008440/OD/NIH HHS/United States ; }, mesh = {Bacteria/*pathogenicity ; Bacterial Infections/*microbiology ; *Host-Pathogen Interactions ; Humans ; *Microbial Consortia ; *Microbial Interactions ; }, abstract = {The study of microbial pathogenesis has been primarily a reductionist science since Koch's principles. Reductionist approaches are essential to identify the causal agents of infectious disease, their molecular mechanisms of action, and potential drug targets, and much of medicine's success in the treatment of infectious disease stems from that approach. But many bacteria-caused diseases cannot be explained by a single bacterium. Several aspects of bacterial pathogenesis will benefit from a more holistic approach that takes into account social interaction among bacteria of the same species and between species in consortia such as the human microbiome. The emerging discipline of sociomicrobiology provides a framework to dissect microbial interactions in single and multi-species communities without compromising mechanistic detail. The study of bacterial pathogenesis can benefit greatly from incorporating concepts from other disciplines such as social evolution theory and microbial ecology, where communities, their interactions with hosts, and with the environment play key roles.}, }
@article {pmid27330858, year = {2016}, author = {Bisanz, JE and Suppiah, P and Thomson, WM and Milne, T and Yeoh, N and Nolan, A and Ettinger, G and Reid, G and Gloor, GB and Burton, JP and Cullinan, MP and Stebbings, SM}, title = {The oral microbiome of patients with axial spondyloarthritis compared to healthy individuals.}, journal = {PeerJ}, volume = {4}, number = {}, pages = {e2095}, pmid = {27330858}, issn = {2167-8359}, abstract = {Background. A loss of mucosal tolerance to the resident microbiome has been postulated in the aetiopathogenesis of spondyloarthritis, thus the purpose of these studies was to investigate microbial communities that colonise the oral cavity of patients with axial spondyloarthritis (AxSpA) and to compare these with microbial profiles of a matched healthy population. Methods. Thirty-nine participants, 17 patients with AxSpA and 22 age and gender-matched disease-free controls were recruited to the study. For patients with AxSpA, disease activity was assessed using the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). All participants underwent a detailed dental examination to assess oral health, including the presence of periodontal disease assessed using probing pocket depth (PPD). Plaque samples were obtained and their bacterial populations were profiled using Ion Torrent sequencing of the V6 region of the 16S rRNA gene. Results.Patients with AxSpA had active disease (BASDAI 4.1 ± 2.1 [mean ± SD]), and a significantly greater prevalence of periodontitis (PPD ≥ 4 mm at ≥4 sites) than controls. Bacterial communities did not differ between the two groups with multiple metrics of α and β diversity considered. Analysis of operational taxonomic units (OTUs) and higher levels of taxonomic assignment did not provide strong evidence of any single taxa associated with AxSpA in the subgingival plaque. Discussion. Although 16S rRNA gene sequencing did not identify specific bacterial profiles associated with AxSpA, there remains the potential for the microbiota to exert functional and metabolic influences in the oral cavity which could be involved in the pathogenesis of AxSpA.}, }
@article {pmid27317164, year = {2016}, author = {Hernandez, CJ and Guss, JD and Luna, M and Goldring, SR}, title = {Links Between the Microbiome and Bone.}, journal = {Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research}, volume = {31}, number = {9}, pages = {1638-1646}, pmid = {27317164}, issn = {1523-4681}, support = {F33 AR065348/AR/NIAMS NIH HHS/United States ; R21 AR068061/AR/NIAMS NIH HHS/United States ; }, mesh = {Animals ; Anti-Bacterial Agents/pharmacology ; Bone and Bones/drug effects/*physiology ; *Gastrointestinal Microbiome/drug effects ; Humans ; Organ Specificity ; Osteogenesis/drug effects ; Probiotics/pharmacology ; }, abstract = {The human microbiome has been shown to influence a number of chronic conditions associated with impaired bone mass and bone quality, including obesity, diabetes, and inflammatory bowel disease. The connection between the microbiome and bone health, however, has not been well studied. The few studies available demonstrate that the microbiome can have a large effect on bone remodeling and bone mass. The gut microbiome is the largest reservoir of microbial organisms in the body and consists of more than a thousand different species interacting with one another in a stable, dynamic equilibrium. How the microbiome can affect organs distant from the gut is not well understood but is believed to occur through regulation of nutrition, regulation of the immune system, and/or translocation of bacterial products across the gut endothelial barrier. Here we review each of these mechanisms and discuss their potential effect on bone remodeling and bone mass. We discuss how preclinical studies of bone-microbiome interactions are challenging because the microbiome is sensitive to genetic background, housing environment, and vendor source. Additionally, although the microbiome exhibits a robust response to external stimuli, it rapidly returns to its original steady state after a disturbance, making it difficult to sustain controlled changes in the microbiome over time periods required to detect alterations in bone remodeling, mass, or structure. Despite these challenges, an understanding of the mechanisms by which the gut microbiome affects bone has the potential to provide insights into the dissociation between fracture risk and bone mineral density in patients including those with obesity, diabetes, or inflammatory bowel disease. In addition, alteration of the gut microbiome has the potential to serve as a biomarker of bone metabolic activity as well as a target for therapies to improve bone structure and quality using pharmaceutical agents or pre- or probiotics. © 2016 American Society for Bone and Mineral Research.}, }
@article {pmid27314511, year = {2016}, author = {Gloor, GB and Reid, G}, title = {Compositional analysis: a valid approach to analyze microbiome high-throughput sequencing data.}, journal = {Canadian journal of microbiology}, volume = {62}, number = {8}, pages = {692-703}, doi = {10.1139/cjm-2015-0821}, pmid = {27314511}, issn = {1480-3275}, mesh = {Canada ; Cluster Analysis ; High-Throughput Nucleotide Sequencing ; Humans ; *Microbiota ; Probiotics ; Sequence Analysis, DNA ; }, abstract = {A workshop held at the 2015 annual meeting of the Canadian Society of Microbiologists highlighted compositional data analysis methods and the importance of exploratory data analysis for the analysis of microbiome data sets generated by high-throughput DNA sequencing. A summary of the content of that workshop, a review of new methods of analysis, and information on the importance of careful analyses are presented herein. The workshop focussed on explaining the rationale behind the use of compositional data analysis, and a demonstration of these methods for the examination of 2 microbiome data sets. A clear understanding of bioinformatics methodologies and the type of data being analyzed is essential, given the growing number of studies uncovering the critical role of the microbiome in health and disease and the need to understand alterations to its composition and function following intervention with fecal transplant, probiotics, diet, and pharmaceutical agents.}, }
@article {pmid27314385, year = {2016}, author = {Cinelli, G and Fabrizi, M and Ravà, L and Ciofi Degli Atti, M and Vernocchi, P and Vallone, C and Pietrantoni, E and Lanciotti, R and Signore, F and Manco, M}, title = {Influence of Maternal Obesity and Gestational Weight Gain on Maternal and Foetal Lipid Profile.}, journal = {Nutrients}, volume = {8}, number = {6}, pages = {}, pmid = {27314385}, issn = {2072-6643}, mesh = {8,11,14-Eicosatrienoic Acid/blood ; Adolescent ; Adult ; Arachidonic Acid/blood ; Birth Weight ; Body Mass Index ; Docosahexaenoic Acids/blood ; Educational Status ; Eicosapentaenoic Acid/blood ; Erythrocytes/chemistry ; Fatty Acids/*blood ; Female ; Fetal Blood/chemistry ; Fetus/*chemistry ; Humans ; Infant, Newborn ; Linoleic Acid/blood ; Male ; Middle Aged ; Mothers ; Obesity/*physiopathology ; Pregnancy ; *Weight Gain ; Young Adult ; alpha-Linolenic Acid/blood ; }, abstract = {Fatty acids (FAs) are fundamental for a foetus's growth, serving as an energy source, structural constituents of cellular membranes and precursors of bioactive molecules, as well as being essential for cell signalling. Long-chain polyunsaturated FAs (LC-PUFAs) are pivotal in brain and visual development. It is of interest to investigate whether and how specific pregnancy conditions, which alter fatty acid metabolism (excessive pre-pregnancy body mass index (BMI) or gestational weight gain (GWG)), affect lipid supply to the foetus. For this purpose, we evaluated the erythrocyte FAs of mothers and offspring (cord-blood) at birth, in relation to pre-pregnancy BMI and GWG. A total of 435 mothers and their offspring (237 males, 51%) were included in the study. Distribution of linoleic acid (LA) and α-linolenic acid (ALA), and their metabolites, arachidonic acid, dihomogamma linoleic (DGLA) and ecosapentanoic acid, was significantly different in maternal and foetal erythrocytes. Pre-pregnancy BMI was significantly associated with maternal percentage of MUFAs (Coeff: -0.112; p = 0.021), LA (Coeff: -0.033; p = 0.044) and DHA (Coeff. = 0.055; p = 0.0016); inadequate GWG with DPA (Coeff: 0.637; p = 0.001); excessive GWG with docosaexahenoic acid (DHA) (Coeff. = -0.714; p = 0.004). Moreover, pre-pregnancy BMI was associated with foetus percentage of PUFAs (Coeff: -0.172; p = 0.009), omega 6 (Coeff: -0.098; p = 0.015) and DHA (Coeff: -0.0285; p = 0.036), even after adjusting for maternal lipids. Our findings show that maternal GWG affects maternal but not foetal lipid profile, differently from pre-pregnancy BMI, which influences both.}, }
@article {pmid27307513, year = {2016}, author = {Secchi, E and Rusconi, R and Buzzaccaro, S and Salek, MM and Smriga, S and Piazza, R and Stocker, R}, title = {Intermittent turbulence in flowing bacterial suspensions.}, journal = {Journal of the Royal Society, Interface}, volume = {13}, number = {119}, pages = {}, pmid = {27307513}, issn = {1742-5662}, mesh = {Bacillus subtilis/*physiology ; Gastrointestinal Microbiome/physiology ; Humans ; Locomotion/*physiology ; Suspensions ; }, abstract = {Dense suspensions of motile bacteria, possibly including the human gut microbiome, exhibit collective dynamics akin to those observed in classic, high Reynolds number turbulence with important implications for chemical and biological transport, yet this analogy has remained primarily qualitative. Here, we present experiments in which a dense suspension of Bacillus subtilis bacteria was flowed through microchannels and the velocity statistics of the flowing suspension were quantified using a recently developed velocimetry technique coupled with vortex identification methods. Observations revealed a robust intermittency phenomenon, whereby the average velocity profile of the suspension fluctuated between a plug-like flow and a parabolic flow profile. This intermittency is a hallmark of the onset of classic turbulence and Lagrangian tracking revealed that it here originates from the presence of transient vortices in the active, collective motion of the bacteria locally reinforcing the externally imposed flow. These results link together two entirely different manifestations of turbulence and show the potential of the microfluidic approach to mimic the environment characteristic of certain niches of the human microbiome.}, }
@article {pmid27306705, year = {2016}, author = {Halden, RU}, title = {Lessons Learned from Probing for Impacts of Triclosan and Triclocarban on Human Microbiomes.}, journal = {mSphere}, volume = {1}, number = {3}, pages = {}, pmid = {27306705}, issn = {2379-5042}, support = {R01 ES015445/ES/NIEHS NIH HHS/United States ; R01 ES020889/ES/NIEHS NIH HHS/United States ; }, abstract = {Despite increasing interest in the effects of triclosan and triclocarban on human biology, current knowledge is still limited on the impact of these additives to antimicrobial personal care products on the human microbiome. A carefully designed recent study published in mSphere by Poole and colleagues [A. C. Poole et al., mSphere 1(3):e00056-15, 2016, http://dx.doi.org/10.1128/mSphere.00056-15] highlights both the power of novel methodologies for microbiome elucidation and the longstanding challenge of employing small-cohort studies to inform risk assessment for chemicals of ubiquitous use in modern society.}, }
@article {pmid27303746, year = {2016}, author = {Poole, AC and Pischel, L and Ley, C and Suh, G and Goodrich, JK and Haggerty, TD and Ley, RE and Parsonnet, J}, title = {Crossover Control Study of the Effect of Personal Care Products Containing Triclosan on the Microbiome.}, journal = {mSphere}, volume = {1}, number = {3}, pages = {}, pmid = {27303746}, issn = {2379-5042}, support = {R01 HD063142/HD/NICHD NIH HHS/United States ; R21 ES023371/ES/NIEHS NIH HHS/United States ; U54 GM104942/GM/NIGMS NIH HHS/United States ; }, abstract = {Commonly prescribed antibiotics are known to alter human microbiota. We hypothesized that triclosan and triclocarban, components of many household and personal care products (HPCPs), may alter the oral and gut microbiota, with potential consequences for metabolic function and weight. In a double-blind, randomized, crossover study, participants were given triclosan- and triclocarban (TCS)-containing or non-triclosan/triclocarban (nTCS)-containing HPCPs for 4 months and then switched to the other products for an additional 4 months. Blood, stool, gingival plaque, and urine samples and weight data were obtained at baseline and at regular intervals throughout the study period. Blood samples were analyzed for metabolic and endocrine markers and urine samples for triclosan. The microbiome in stool and oral samples was then analyzed. Although there was a significant difference in the amount of triclosan in the urine between the TCS and nTCS phases, no differences were found in microbiome composition, metabolic or endocrine markers, or weight. Though this study was limited by the small sample size and imprecise administration of HPCPs, triclosan at physiologic levels from exposure to HPCPs does not appear to have a significant or important impact on human oral or gut microbiome structure or on a panel of metabolic markers. IMPORTANCE Triclosan and triclocarban are commonly used commercial microbicides found in toothpastes and soaps. It is unknown what effects these chemicals have on the human microbiome or on endocrine function. From this randomized crossover study, it appears that routine personal care use of triclosan and triclocarban neither exerts a major influence on microbial communities in the gut and mouth nor alters markers of endocrine function in humans.}, }
@article {pmid27303377, year = {2016}, author = {Jeraldo, P and Hernandez, A and Nielsen, HB and Chen, X and White, BA and Goldenfeld, N and Nelson, H and Alhquist, D and Boardman, L and Chia, N}, title = {Capturing One of the Human Gut Microbiome's Most Wanted: Reconstructing the Genome of a Novel Butyrate-Producing, Clostridial Scavenger from Metagenomic Sequence Data.}, journal = {Frontiers in microbiology}, volume = {7}, number = {}, pages = {783}, pmid = {27303377}, issn = {1664-302X}, support = {P30 DK084567/DK/NIDDK NIH HHS/United States ; R01 CA179243/CA/NCI NIH HHS/United States ; }, abstract = {The role of the microbiome in health and disease is attracting great attention, yet we still know little about some of the most prevalent microorganisms inside our bodies. Several years ago, Human Microbiome Project (HMP) researchers generated a list of "most wanted" taxa: bacteria both prevalent among healthy volunteers and distantly related to any sequenced organisms. Unfortunately, the challenge of assembling high-quality genomes from a tangle of metagenomic reads has slowed progress in learning about these uncultured bacteria. Here, we describe how recent advances in sequencing and analysis allowed us to assemble "most wanted" genomes from metagenomic data collected from four stool samples. Using a combination of both de novo and guided assembly methods, we assembled and binned over 100 genomes from an initial data set of over 1,300 Gbp. One of these genome bins, which met HMP's criteria for a "most wanted" taxa, contained three essentially complete genomes belonging to a previously uncultivated species. This species is most closely related to Eubacterium desmolans and the clostridial cluster IV/Clostridium leptum subgroup species Butyricicoccus pullicaecorum (71-76% average nucleotide identity). Gene function analysis indicates that the species is an obligate anaerobe, forms spores, and produces the anti-inflammatory short-chain fatty acids acetate and butyrate. It also appears to take up metabolically costly molecules such as cobalamin, methionine, and branch-chained amino acids from the environment, and to lack virulence genes. Thus, the evidence is consistent with a secondary degrader that occupies a host-dependent, nutrient-scavenging niche within the gut; its ability to produce butyrate, which is thought to play an anti-inflammatory role, makes it intriguing for the study of diseases such as colon cancer and inflammatory bowel disease. In conclusion, we have assembled essentially complete genomes from stool metagenomic data, yielding valuable information about uncultured organisms' metabolic and ecologic niches, factors that may be required to successfully culture these bacteria, and their role in maintaining health and causing disease.}, }
@article {pmid27279224, year = {2016}, author = {Bashan, A and Gibson, TE and Friedman, J and Carey, VJ and Weiss, ST and Hohmann, EL and Liu, YY}, title = {Universality of human microbial dynamics.}, journal = {Nature}, volume = {534}, number = {7606}, pages = {259-262}, pmid = {27279224}, issn = {1476-4687}, support = {R01 HL091528/HL/NHLBI NIH HHS/United States ; }, mesh = {Clostridioides difficile/physiology ; Clostridium Infections/microbiology ; Computer Simulation ; Cross-Sectional Studies ; Datasets as Topic ; *Ecosystem ; Environment ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/physiology ; Healthy Volunteers ; Humans ; Intestines/microbiology ; Metagenomics ; Microbiota/*physiology ; Mouth/microbiology ; Organ Specificity ; Skin/microbiology ; Species Specificity ; }, abstract = {Human-associated microbial communities have a crucial role in determining our health and well-being, and this has led to the continuing development of microbiome-based therapies such as faecal microbiota transplantation. These microbial communities are very complex, dynamic and highly personalized ecosystems, exhibiting a high degree of inter-individual variability in both species assemblages and abundance profiles. It is not known whether the underlying ecological dynamics of these communities, which can be parameterized by growth rates, and intra- and inter-species interactions in population dynamics models, are largely host-independent (that is, universal) or host-specific. If the inter-individual variability reflects host-specific dynamics due to differences in host lifestyle, physiology or genetics, then generic microbiome manipulations may have unintended consequences, rendering them ineffective or even detrimental. Alternatively, microbial ecosystems of different subjects may exhibit universal dynamics, with the inter-individual variability mainly originating from differences in the sets of colonizing species. Here we develop a new computational method to characterize human microbial dynamics. By applying this method to cross-sectional data from two large-scale metagenomic studies--the Human Microbiome Project and the Student Microbiome Project--we show that gut and mouth microbiomes display pronounced universal dynamics, whereas communities associated with certain skin sites are probably shaped by differences in the host environment. Notably, the universality of gut microbial dynamics is not observed in subjects with recurrent Clostridium difficile infection but is observed in the same set of subjects after faecal microbiota transplantation. These results fundamentally improve our understanding of the processes that shape human microbial ecosystems, and pave the way to designing general microbiome-based therapies.}, }
@article {pmid27274912, year = {2016}, author = {Moos, WH and Faller, DV and Harpp, DN and Kanara, I and Pernokas, J and Powers, WR and Steliou, K}, title = {Microbiota and Neurological Disorders: A Gut Feeling.}, journal = {BioResearch open access}, volume = {5}, number = {1}, pages = {137-145}, pmid = {27274912}, issn = {2164-7844}, abstract = {In the past century, noncommunicable diseases have surpassed infectious diseases as the principal cause of sickness and death, worldwide. Trillions of commensal microbes live in and on our body, and constitute the human microbiome. The vast majority of these microorganisms are maternally derived and live in the gut, where they perform functions essential to our health and survival, including: digesting food, activating certain drugs, producing short-chain fatty acids (which help to modulate gene expression by inhibiting the deacetylation of histone proteins), generating anti-inflammatory substances, and playing a fundamental role in the induction, training, and function of our immune system. Among the many roles the microbiome ultimately plays, it mitigates against untoward effects from our exposure to the environment by forming a biotic shield between us and the outside world. The importance of physical activity coupled with a balanced and healthy diet in the maintenance of our well-being has been recognized since antiquity. However, it is only recently that characterization of the host-microbiome intermetabolic and crosstalk pathways has come to the forefront in studying therapeutic design. As reviewed in this report, synthetic biology shows potential in developing microorganisms for correcting pathogenic dysbiosis (gut microbiota-host maladaptation), although this has yet to be proven. However, the development and use of small molecule drugs have a long and successful history in the clinic, with small molecule histone deacetylase inhibitors representing one relevant example already approved to treat cancer and other disorders. Moreover, preclinical research suggests that epigenetic treatment of neurological conditions holds significant promise. With the mouth being an extension of the digestive tract, it presents a readily accessible diagnostic site for the early detection of potential unhealthy pathogens resident in the gut. Taken together, the data outlined herein provide an encouraging roadmap toward important new medicines and companion diagnostic platforms in a wide range of therapeutic indications.}, }
@article {pmid27255739, year = {2016}, author = {Brooks, JP}, title = {Challenges for case-control studies with microbiome data.}, journal = {Annals of epidemiology}, volume = {26}, number = {5}, pages = {336-341.e1}, doi = {10.1016/j.annepidem.2016.03.009}, pmid = {27255739}, issn = {1873-2585}, support = {U54 HD080784/HD/NICHD NIH HHS/United States ; P60 MD002256/MD/NIMHD NIH HHS/United States ; }, mesh = {*Biodiversity ; Biomedical Research/methods ; *Case-Control Studies ; Epidemiologic Methods ; Female ; Humans ; Male ; Microbiota/genetics/*physiology ; Needs Assessment ; *Quality Control ; }, abstract = {PURPOSE: In case-control studies of the human microbiome, the goal is to evaluate whether cases differ from controls in the microbiome composition of a particular body habitat and which taxa are responsible for the differences. These studies leverage sequencing technology and spectroscopy that provide new measurements of the microbiome.<br><br>METHODS: Three challenges in conducting reproducible microbiome research using a case-control design are compensating for differences in observed and actual microbial community composition, detecting "rare" taxa in microbial communities, and choosing properly powered analysis methods. The significance of each challenge, evaluation of commonly held views, analysis of unanswered questions, and suggestions of strategies for solutions are discussed.<br><br>RESULTS: Understanding the effects of these choices on case-control analyses has been underappreciated, with an implicit assumption that further advances in technology will address all the current shortcomings.<br><br>CONCLUSIONS: It is recommended that research on the human microbiome include positive and negative control experiments to provide insight into bias, contamination, and technical variation. Research protocols such as these may afford a better opportunity to make quantitative and qualitative adjustments to data, thereby reducing the risk of falsely positive results, increasing power to discover true disease determinants, and enhancing interpretation across studies.}, }
@article {pmid27255738, year = {2016}, author = {Tsilimigras, MC and Fodor, AA}, title = {Compositional data analysis of the microbiome: fundamentals, tools, and challenges.}, journal = {Annals of epidemiology}, volume = {26}, number = {5}, pages = {330-335}, doi = {10.1016/j.annepidem.2016.03.002}, pmid = {27255738}, issn = {1873-2585}, mesh = {High-Throughput Nucleotide Sequencing/methods ; Humans ; Metagenomics/*methods ; Microbiota/*genetics ; *Models, Statistical ; Needs Assessment ; RNA, Ribosomal, 16S/*genetics ; Selection Bias ; }, abstract = {PURPOSE: Human microbiome studies are within the realm of compositional data with the absolute abundances of microbes not recoverable from sequence data alone. In compositional data analysis, each sample consists of proportions of various organisms with a sum constrained to a constant. This simple feature can lead traditional statistical treatments when naively applied to produce errant results and spurious correlations.<br><br>METHODS: We review the origins of compositionality in microbiome data, the theory and usage of compositional data analysis in this setting and some recent attempts at solutions to these problems.<br><br>RESULTS: Microbiome sequence data sets are typically high dimensional, with the number of taxa much greater than the number of samples, and sparse as most taxa are only observed in a small number of samples. These features of microbiome sequence data interact with compositionality to produce additional challenges in analysis.<br><br>CONCLUSIONS: Despite sophisticated approaches to statistical transformation, the analysis of compositional data may remain a partially intractable problem, limiting inference. We suggest that current research needs include better generation of simulated data and further study of how the severity of compositional effects changes when sampling microbial communities of widely differing diversity.}, }
@article {pmid27245597, year = {2018}, author = {Cundell, AM}, title = {Microbial Ecology of the Human Skin.}, journal = {Microbial ecology}, volume = {76}, number = {1}, pages = {113-120}, pmid = {27245597}, issn = {1432-184X}, mesh = {Age Factors ; Anti-Bacterial Agents ; Axilla/microbiology ; Bacteria/classification/genetics ; Bacterial Physiological Phenomena ; *Biodiversity ; Cosmetics ; *Ecology ; *Ecosystem ; Fungi/classification/genetics/physiology ; Genes, Bacterial/genetics ; Genes, Fungal/genetics ; Health Status ; Homeostasis ; Humans ; Injections ; Microbiota/genetics/*physiology ; Perineum/microbiology ; RNA, Ribosomal, 16S/genetics ; Sex Factors ; Skin/*microbiology ; Toe Joint/microbiology ; Vaccination ; }, abstract = {This review article on the skin microbiota was written in response to recent advances that transitioned from culture methods to PCR amplification and sequencing of bacterial and fungal genes as a result of the Human Microbiome Project. This transition enables the investigation of the full diversity of microorganisms inhabiting human skin. The skin provides a range of habitats with different microbiota associated with the three major regions of the skin, namely the moist axilla, perineum, and toe webs; oily or sebaceous head, neck, and trunk; and dry forearms and legs. These new culture-independent tools are revealing the diversity of the human skin microbiota in the different locations of the body and with skin depth. These tools should lead to a better understanding of the state of homeostasis between the microbiota and the host and the overall functionality of that microbiota.}, }
@article {pmid29878736, year = {2016}, author = {Lin, Z and Zu, XP and Xie, HS and Jin, HZ and Yang, N and Liu, XR and Zhang, WD}, title = {[Research progress in mechanism of intestinal microorganisms in human diseases].}, journal = {Yao xue xue bao = Acta pharmaceutica Sinica}, volume = {51}, number = {6}, pages = {843-852}, pmid = {29878736}, issn = {0513-4870}, mesh = {*Gastrointestinal Microbiome ; Humans ; Intestines/*microbiology ; *Metagenomics ; Symbiosis ; }, abstract = {The international cooperated research projects of the Human Microbiome Project (HMP) and Metagenomics of The Human Intestinal Tract (MetaHIT) were officially launched in 2007, which indicated the era of metagenomics research of microorganisms in human gastrointestinal tract had been coming. Each human body is a superorganism which is composed of 90% commensal microorganisms, especially the intestinal microorganisms. The intestinal microorganisms play an important role on health maintenance since they are involved in the absorption and metabolism of nutrients in the human bodies. Herein, we review the research progress in the mechanism of intestinal microorganisms in human diseases. Our purpose is to provide novel ideas on human health and therapeutic targets of diseases.}, }
@article {pmid27243592, year = {2016}, author = {Ashton, JJ and Beattie, RM and Ennis, S and Cleary, DW}, title = {Analysis and Interpretation of the Human Microbiome.}, journal = {Inflammatory bowel diseases}, volume = {22}, number = {7}, pages = {1713-1722}, doi = {10.1097/MIB.0000000000000809}, pmid = {27243592}, issn = {1536-4844}, mesh = {Bacteria/*genetics ; *Biomedical Research/methods ; DNA, Bacterial/*analysis ; Genomics ; Humans ; *Microbiota ; RNA, Bacterial/*analysis ; RNA, Ribosomal, 16S/*analysis ; Sequence Analysis, DNA/methods ; Sequence Analysis, RNA ; Software ; }, abstract = {Microbiome research has experienced an unprecedented level of growth over the last decade. This is largely due to revolutionary developments in, and accessibility to, DNA sequencing technologies that have enabled laboratories with even modest budgets to undertake projects. Study of the human microbiome in particular has seen a surge in interest, and although a lot of time and money has been focused on health and disease, the clinical interpretation of these data and the ability of clinicians to understand these studies in the context of disease are less straightforward. Conditions such as inflammatory bowel disease, asthma, and cancer have seen a huge increase in research focused on the role of microbiome in disease pathogenesis, but the ability of clinicians to appraise and use these data is largely lacking. The purpose of this article is to provide an introduction for clinicians and nonclinicians wishing to learn about and engage in microbiome research. It details the background of microbiome research and discusses the process of generating 16S rRNA sequencing data, the most commonly used method for microbiome analysis. We discuss the interpretation of results in a clinical context, commonly used metrics for analysis and discuss future impact and direction for microbiome research. The meteoric rise of genomic medicine to the brink of routine clinical use should be seen as a blueprint for the microbiome; the ability for physicians to understand and interpret these data is vital to this growth and aiding clinicians (and researchers) to participate in further microbiome research.}, }
@article {pmid27239563, year = {2016}, author = {Noecker, C and Eng, A and Srinivasan, S and Theriot, CM and Young, VB and Jansson, JK and Fredricks, DN and Borenstein, E}, title = {Metabolic Model-Based Integration of Microbiome Taxonomic and Metabolomic Profiles Elucidates Mechanistic Links between Ecological and Metabolic Variation.}, journal = {mSystems}, volume = {1}, number = {1}, pages = {}, pmid = {27239563}, issn = {2379-5077}, support = {DP2 AT007802/AT/NCCIH NIH HHS/United States ; K01 GM109236/GM/NIGMS NIH HHS/United States ; R01 AI061628/AI/NIAID NIH HHS/United States ; R01 HG005816/HG/NHGRI NIH HHS/United States ; }, abstract = {UNLABELLED: Multiple molecular assays now enable high-throughput profiling of the ecology, metabolic capacity, and activity of the human microbiome. However, to date, analyses of such multi-omic data typically focus on statistical associations, often ignoring extensive prior knowledge of the mechanisms linking these various facets of the microbiome. Here, we introduce a comprehensive framework to systematically link variation in metabolomic data with community composition by utilizing taxonomic, genomic, and metabolic information. Specifically, we integrate available and inferred genomic data, metabolic network modeling, and a method for predicting community-wide metabolite turnover to estimate the biosynthetic and degradation potential of a given community. Our framework then compares variation in predicted metabolic potential with variation in measured metabolites' abundances to evaluate whether community composition can explain observed shifts in the community metabolome, and to identify key taxa and genes contributing to the shifts. Focusing on two independent vaginal microbiome data sets, each pairing 16S community profiling with large-scale metabolomics, we demonstrate that our framework successfully recapitulates observed variation in 37% of metabolites. Well-predicted metabolite variation tends to result from disease-associated metabolism. We further identify several disease-enriched species that contribute significantly to these predictions. Interestingly, our analysis also detects metabolites for which the predicted variation negatively correlates with the measured variation, suggesting environmental control points of community metabolism. Applying this framework to gut microbiome data sets reveals similar trends, including prediction of bile acid metabolite shifts. This framework is an important first step toward a system-level multi-omic integration and an improved mechanistic understanding of the microbiome activity and dynamics in health and disease.<br><br>IMPORTANCE: Studies characterizing both the taxonomic composition and metabolic profile of various microbial communities are becoming increasingly common, yet new computational methods are needed to integrate and interpret these data in terms of known biological mechanisms. Here, we introduce an analytical framework to link species composition and metabolite measurements, using a simple model to predict the effects of community ecology on metabolite concentrations and evaluating whether these predictions agree with measured metabolomic profiles. We find that a surprisingly large proportion of metabolite variation in the vaginal microbiome can be predicted based on species composition (including dramatic shifts associated with disease), identify putative mechanisms underlying these predictions, and evaluate the roles of individual bacterial species and genes. Analysis of gut microbiome data using this framework recovers similar community metabolic trends. This framework lays the foundation for model-based multi-omic integrative studies, ultimately improving our understanding of microbial community metabolism.}, }
@article {pmid27216717, year = {2016}, author = {Leung, MH and Lee, PK}, title = {The roles of the outdoors and occupants in contributing to a potential pan-microbiome of the built environment: a review.}, journal = {Microbiome}, volume = {4}, number = {1}, pages = {21}, pmid = {27216717}, issn = {2049-2618}, mesh = {*Air Microbiology ; Air Pollutants/*analysis ; Air Pollution, Indoor/*analysis ; Bacteria/*classification/genetics ; Base Sequence ; Environment ; Geography ; High-Throughput Nucleotide Sequencing ; Humans ; Intestines/microbiology ; Microbiota/*genetics ; Mouth/microbiology ; Sequence Analysis, DNA ; Skin/microbiology ; }, abstract = {Recent high-throughput sequencing technology has led to an expansion of knowledge regarding the microbial communities (microbiome) across various built environments (BEs). The microbiome of the BE is dependent upon building factors and conditions that govern how outdoor microbes enter and persist in the BE. Additionally, occupants are crucial in shaping the microbiome of the BE by releasing human-associated microorganisms and resuspending microbes on floors and surfaces. Therefore, both the outdoors and occupants act as major sources of microorganisms found in the BE. However, most characterizations of the microbiome of the BE have been conducted in the Western world. Notably, outdoor locations and population groups present geographical variations in outdoor and human microbiomes, respectively. Given the influences of the outdoor and human microbiomes on BE microbiology, and the geographical variations in outdoor and human microbiomes, it is likely that the microbiomes of BEs also vary by location. The summation of microbiomes between BEs contribute to a potential BE pan-microbiome, which will both consist of microbes that are ubiquitous in indoor environments around the world, and microbes that appear to be endemic to particular geographical locations. Importantly, the BE pan-microbiome can potentially question the global application of our current views on indoor microbiology. In this review, we first provide an assessment on the roles of building and occupant properties on shaping the microbiome of the BE. This is then followed by a description of geographical variations in the microbiomes of the outdoors and humans, the two main sources of microbes in BEs. We present evidence of differences in microbiomes of BEs around the world, demonstrating the existence of a global pan-microbiome of the BE that is larger than the microbiome of any single indoor environment. Finally, we discuss the significance of understanding the BE pan-microbiome and identifying universal and location-specific relationships between building and occupant characteristics and indoor microbiology. This review highlights the much needed efforts towards determining the pan-microbiome of the BE, thereby identifying general and location-specific links between the microbial communities of the outdoors, human, and BE ecosystems, ultimately improving the health, comfort, and productivity of occupants around the world.}, }
@article {pmid27200178, year = {2016}, author = {Ricaboni, D and Mailhe, M and Khelaifia, S and Raoult, D and Million, M}, title = {Romboutsia timonensis, a new species isolated from human gut.}, journal = {New microbes and new infections}, volume = {12}, number = {}, pages = {6-7}, pmid = {27200178}, issn = {2052-2975}, abstract = {The exploration of the human microbiome was recently revolutionized by microbial culturomics and taxonogenomics. Thanks to this approach, we report here the main characteristics of Romboutsia timonensis strain Marseille-P326, a new bacterium isolated from the right human colon by colonoscopy in a 63-year-old French man with severe anaemia with melaena.}, }
@article {pmid27195280, year = {2016}, author = {Bahrndorff, S and Alemu, T and Alemneh, T and Lund Nielsen, J}, title = {The Microbiome of Animals: Implications for Conservation Biology.}, journal = {International journal of genomics}, volume = {2016}, number = {}, pages = {5304028}, pmid = {27195280}, issn = {2314-436X}, abstract = {In recent years the human microbiome has become a growing area of research and it is becoming clear that the microbiome of humans plays an important role for human health. Extensive research is now going into cataloging and annotating the functional role of the human microbiome. The ability to explore and describe the microbiome of any species has become possible due to new methods for sequencing. These techniques allow comprehensive surveys of the composition of the microbiome of nonmodel organisms of which relatively little is known. Some attention has been paid to the microbiome of insect species including important vectors of pathogens of human and veterinary importance, agricultural pests, and model species. Together these studies suggest that the microbiome of insects is highly dependent on the environment, species, and populations and affects the fitness of species. These fitness effects can have important implications for the conservation and management of species and populations. Further, these results are important for our understanding of invasion of nonnative species, responses to pathogens, and responses to chemicals and global climate change in the present and future.}, }
@article {pmid27182288, year = {2016}, author = {Thomas-White, K and Brady, M and Wolfe, AJ and Mueller, ER}, title = {The bladder is not sterile: History and current discoveries on the urinary microbiome.}, journal = {Current bladder dysfunction reports}, volume = {11}, number = {1}, pages = {18-24}, pmid = {27182288}, issn = {1931-7212}, support = {R01 DK104718/DK/NIDDK NIH HHS/United States ; R21 DK097435/DK/NIDDK NIH HHS/United States ; }, abstract = {In the human body, there are 10 bacterial cells for every one human cell. This fact highlights the importance of the National institutes of Health's initiative to map the human microbiome. The Human Microbiome Project was the first large-scale mapping of the human microbiome of 5 body sites: GI tract, mouth, vagina, skin and nasal cavity using culture-independent methods. The bladder was not originally tested because it was considered to be sterile and there were complexities regarding sample collection. Over the last couple years our team along with other investigators have shown that a urinary microbiome exists and for most individuals it plays a protective role.}, }
@article {pmid27180113, year = {2016}, author = {Hanson, BM and Weinstock, GM}, title = {The importance of the microbiome in epidemiologic research.}, journal = {Annals of epidemiology}, volume = {26}, number = {5}, pages = {301-305}, doi = {10.1016/j.annepidem.2016.03.008}, pmid = {27180113}, issn = {1873-2585}, mesh = {*Epidemiologic Studies ; Humans ; Microbiota/drug effects/*physiology ; Reproducibility of Results ; *Research Design ; }, abstract = {PURPOSE: The human microbiome is the community of microorganisms that live on and in the body. Currently, most applications of microbiome analysis derive from the perspective of discovery and characterization. The completion of the NIH Human Microbiome and the European MetaHIT projects will change the focus to studying the role of the microbiome on human health and disease.<br><br>METHODS: Recent developments in technology and bioinformatics have afforded an opportunity to explore more fully the importance of community structure, detection of pathogens, and community interactions. The current state of microbiome research in terms of effect size, power calculations, how stratification on community classes can increase this power, and the importance of study design and power in reproducibility is reviewed.<br><br>RESULTS: Work is needed to characterize microbiome development, ecological stability, and variation. Development and implementation of variance stabilization techniques should replace rarefaction of data, which reduces study power, in future research.<br><br>CONCLUSIONS: Epidemiologists have most of the tools necessary to explore the relationship between the microbiome and human health. Further development of tools for large-scale multivariate data sets will be helpful. Applying the methods of epidemiology will be critical in translating research results to preventive interventions and population health.}, }
@article {pmid27180112, year = {2016}, author = {Robinson, CK and Brotman, RM and Ravel, J}, title = {Intricacies of assessing the human microbiome in epidemiologic studies.}, journal = {Annals of epidemiology}, volume = {26}, number = {5}, pages = {311-321}, pmid = {27180112}, issn = {1873-2585}, support = {K01 AI080974/AI/NIAID NIH HHS/United States ; R01 AI116799/AI/NIAID NIH HHS/United States ; U19 AI084044/AI/NIAID NIH HHS/United States ; }, mesh = {Biomedical Research/*methods ; *Epidemiologic Studies ; Genes, rRNA/*genetics/physiology ; Humans ; Microbiota/*genetics/physiology ; Molecular Biology ; Reproducibility of Results ; }, abstract = {PURPOSE: In the past decade, remarkable relationships have been documented between dysbiosis of the human microbiota and adverse health outcomes. This review seeks to highlight some of the challenges and pitfalls that may be encountered during all stages of microbiota research, from study design and sample collection, to nucleic acid extraction and sequencing, and bioinformatic and statistical analysis.<br><br>METHODS: Literature focused on human microbiota research was reviewed and summarized.<br><br>RESULTS: Although most studies have focused on surveying the composition of the microbiota, fewer have explored the causal roles of these bacteria, archaea, viruses, and fungi in affecting disease states. Microbiome research is in its relatively early years and many aspects remain challenging, including the complexity and personalized aspects of microbial communities, the influence of exogenous and often confounding factors, the need to apply fundamental principles of ecology and epidemiology, the necessity for new software tools, and the rapidly evolving genomic, technological, and analytical landscapes.<br><br>CONCLUSIONS: Incorporating human microbiome research in large epidemiologic studies will soon help us unravel the intricate relationships that we have with our microbial partners and provide interventional opportunities to improve human health.}, }
@article {pmid27173935, year = {2016}, author = {Goodrich, JK and Davenport, ER and Beaumont, M and Jackson, MA and Knight, R and Ober, C and Spector, TD and Bell, JT and Clark, AG and Ley, RE}, title = {Genetic Determinants of the Gut Microbiome in UK Twins.}, journal = {Cell host &amp; microbe}, volume = {19}, number = {5}, pages = {731-743}, pmid = {27173935}, issn = {1934-6069}, support = {MR/N01183X/1/MRC_/Medical Research Council/United Kingdom ; MR/N030125/1/MRC_/Medical Research Council/United Kingdom ; DP2 OD007444/OD/NIH HHS/United States ; R01 DK093595/DK/NIDDK NIH HHS/United States ; P30 DK020541/DK/NIDDK NIH HHS/United States ; F32 DK109595/DK/NIDDK NIH HHS/United States ; /WT_/Wellcome Trust/United Kingdom ; }, mesh = {Base Sequence ; Female ; Gastrointestinal Microbiome/*genetics ; Genetic Variation ; Humans ; Male ; Microbial Consortia/*genetics ; *Twins ; United Kingdom ; }, abstract = {Studies in mice and humans have revealed intriguing associations between host genetics and the microbiome. Here we report a 16S rRNA-based analysis of the gut microbiome in 1,126 twin pairs, a subset of which was previously reported. Tripling the sample narrowed the confidence intervals around heritability estimates and uncovered additional heritable taxa, some of which are validated in other studies. Repeat sampling of subjects showed heritable taxa to be temporally stable. A candidate gene approach uncovered associations between heritable taxa and genes related to diet, metabolism, and olfaction. We replicate an association between Bifidobacterium and the lactase (LCT) gene locus and identify an association between the host gene ALDH1L1 and the bacteria SHA-98, suggesting a link between formate production and blood pressure. Additional genes detected are involved in barrier defense and self/non-self recognition. Our results indicate that diet-sensing, metabolism, and immune defense are important drivers of human-microbiome co-evolution.}, }
@article {pmid27158310, year = {2016}, author = {Robertson-Albertyn, S and Hardee, E and Stanley-Wall, NR}, title = {Microbe Motels: An Interactive Method to Introduce the Human Microbiome.}, journal = {Journal of microbiology &amp; biology education}, volume = {17}, number = {2}, pages = {282-283}, pmid = {27158310}, issn = {1935-7877}, support = {BB/I019464/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; BB/L006804/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; }, }
@article {pmid27148241, year = {2016}, author = {Utter, DR and Mark Welch, JL and Borisy, GG}, title = {Individuality, Stability, and Variability of the Plaque Microbiome.}, journal = {Frontiers in microbiology}, volume = {7}, number = {}, pages = {564}, pmid = {27148241}, issn = {1664-302X}, support = {R01 DE022586/DE/NIDCR NIH HHS/United States ; }, abstract = {Dental plaque is a bacterial biofilm composed of a characteristic set of organisms. Relatively little information from cultivation-independent, high-throughput analyses has been published on the temporal dynamics of the dental plaque microbiome. We used Minimum Entropy Decomposition, an information theory-based approach similar to oligotyping that provides single-nucleotide resolution, to analyze a previously published time series data set and investigate the dynamics of the plaque microbiome at various analytic and taxonomic levels. At both the genus and 97% Operational Taxonomic Unit (OTU) levels of resolution, the range of variation within each individual overlapped that of other individuals in the data set. When analyzed at the oligotype level, however, the overlap largely disappeared, showing that single-nucleotide resolution enables differentiation of individuals from one another without ambiguity. The overwhelming majority of the plaque community in all samples was made up of bacteria from a moderate number of plaque-typical genera, indicating that the overall community framework is shared among individuals. Each of these genera fluctuated in abundance around a stable mean that varied between individuals, with some genera having higher inter-individual variability than others. Thus, at the genus level, differences between individuals lay not in the identity of the major genera but in consistently differing proportions of these genera from mouth to mouth. However, at the oligotype level, we detected oligotype "fingerprints," a highly individual-specific set of persistently abundant oligotypes fluctuating around a stable mean over time. For example, within the genus Corynebacterium, more than a dozen oligotypes were detectable in each individual, of which a different subset reached high abundance in any given person. This pattern suggests that each mouth contains a subtly different community of organisms. We also compared the Chinese plaque community characterized here to previously characterized Western plaque communities, as represented by analyses of data emerging from the Human Microbiome Project, and found no major differences between Chinese and Western supragingival plaque. In conclusion, we found the plaque microbiome to be highly individualized at the oligotype level and characterized by stability of community membership, with variability in the relative abundance of community members between individuals and over time.}, }
@article {pmid27148183, year = {2016}, author = {Boix-Amorós, A and Collado, MC and Mira, A}, title = {Relationship between Milk Microbiota, Bacterial Load, Macronutrients, and Human Cells during Lactation.}, journal = {Frontiers in microbiology}, volume = {7}, number = {}, pages = {492}, pmid = {27148183}, issn = {1664-302X}, abstract = {Human breast milk is considered the optimal nutrition for infants, providing essential nutrients and a broad range of bioactive compounds, as well as its own microbiota. However, the interaction among those components and the biological role of milk microorganisms is still uncovered. Thus, our aim was to identify the relationships between milk microbiota composition, bacterial load, macronutrients, and human cells during lactation. Bacterial load was estimated in milk samples from a total of 21 healthy mothers through lactation time by bacteria-specific qPCR targeted to the single-copy gene fusA. Milk microbiome composition and diversity was estimated by 16S-pyrosequencing and the structure of these bacteria in the fluid was studied by flow cytometry, qPCR, and microscopy. Fat, protein, lactose, and dry extract of milk as well as the number of somatic cells were also analyzed. We observed that milk bacterial communities were generally complex, and showed individual-specific profiles. Milk microbiota was dominated by Staphylococcus, Pseudomonas, Streptococcus, and Acinetobacter. Staphylococcus aureus was not detected in any of these samples from healthy mothers. There was high variability in composition and number of bacteria per milliliter among mothers and in some cases even within mothers at different time points. The median bacterial load was 10(6) bacterial cells/ml through time, higher than those numbers reported by 16S gene PCR and culture methods. Furthermore, milk bacteria were present in a free-living, "planktonic" state, but also in equal proportion associated to human immune cells. There was no correlation between bacterial load and the amount of immune cells in milk, strengthening the idea that milk bacteria are not sensed as an infection by the immune system.}, }
@article {pmid27146150, year = {2016}, author = {Nayak, RR and Turnbaugh, PJ}, title = {Mirror, mirror on the wall: which microbiomes will help heal them all?.}, journal = {BMC medicine}, volume = {14}, number = {}, pages = {72}, pmid = {27146150}, issn = {1741-7015}, support = {R01HL122593/HL/NHLBI NIH HHS/United States ; T32 AR007304/AR/NIAMS NIH HHS/United States ; 5T32AR007304-37/AR/NIAMS NIH HHS/United States ; P30 DK098722/DK/NIDDK NIH HHS/United States ; R01 HL122593/HL/NHLBI NIH HHS/United States ; }, mesh = {*Gastrointestinal Microbiome/drug effects/genetics ; Genome, Human ; Humans ; Metagenomics/methods ; *Microbial Consortia/drug effects/genetics ; Precision Medicine ; }, abstract = {BACKGROUND: Clinicians have known for centuries that there is substantial variability between patients in their response to medications-some individuals exhibit a miraculous recovery while others fail to respond at all. Still others experience dangerous side effects. The hunt for the factors responsible for this variation has been aided by the ability to sequence the human genome, but this just provides part of the picture. Here, we discuss the emerging field of study focused on the human microbiome and how it may help to better predict drug response and improve the treatment of human disease.<br><br>DISCUSSION: Various clinical disciplines characterize drug response using either continuous or categorical descriptors that are then correlated to environmental and genetic risk factors. However, these approaches typically ignore the microbiome, which can directly metabolize drugs into downstream metabolites with altered activity, clearance, and/or toxicity. Variations in the ability of each individual's microbiome to metabolize drugs may be an underappreciated source of differences in clinical response. Complementary studies in humans and animal models are necessary to elucidate the mechanisms responsible and to test the feasibility of identifying microbiome-based biomarkers of treatment outcomes. We propose that the predictive power of genetic testing could be improved by taking a more comprehensive view of human genetics that encompasses our human and microbial genomes. Furthermore, unlike the human genome, the microbiome is rapidly altered by diet, pharmaceuticals, and other interventions, providing the potential to improve patient care by re-shaping our associated microbial communities.}, }
@article {pmid27144353, year = {2016}, author = {Browne, HP and Forster, SC and Anonye, BO and Kumar, N and Neville, BA and Stares, MD and Goulding, D and Lawley, TD}, title = {Culturing of 'unculturable' human microbiota reveals novel taxa and extensive sporulation.}, journal = {Nature}, volume = {533}, number = {7604}, pages = {543-546}, pmid = {27144353}, issn = {1476-4687}, support = {PF451/MRC_/Medical Research Council/United Kingdom ; 098051/WT_/Wellcome Trust/United Kingdom ; /WT_/Wellcome Trust/United Kingdom ; G1000214/MRC_/Medical Research Council/United Kingdom ; MR/K000551/1/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Anaerobiosis ; Bacteria/*classification/drug effects/genetics/*growth &amp; development/isolation &amp; purification ; *Bacterial Typing Techniques ; Cell Culture Techniques ; Feces/microbiology ; Gastrointestinal Microbiome/drug effects/genetics/*physiology ; Genome, Bacterial/genetics ; Health ; Humans ; Metagenome/genetics ; Metagenomics ; Oxygen/metabolism/pharmacology ; Phenotype ; Phylogeny ; Sequence Analysis, DNA ; Species Specificity ; Spores, Bacterial/classification/drug effects/growth &amp; development ; }, abstract = {Our intestinal microbiota harbours a diverse bacterial community required for our health, sustenance and wellbeing. Intestinal colonization begins at birth and climaxes with the acquisition of two dominant groups of strict anaerobic bacteria belonging to the Firmicutes and Bacteroidetes phyla. Culture-independent, genomic approaches have transformed our understanding of the role of the human microbiome in health and many diseases. However, owing to the prevailing perception that our indigenous bacteria are largely recalcitrant to culture, many of their functions and phenotypes remain unknown. Here we describe a novel workflow based on targeted phenotypic culturing linked to large-scale whole-genome sequencing, phylogenetic analysis and computational modelling that demonstrates that a substantial proportion of the intestinal bacteria are culturable. Applying this approach to healthy individuals, we isolated 137 bacterial species from characterized and candidate novel families, genera and species that were archived as pure cultures. Whole-genome and metagenomic sequencing, combined with computational and phenotypic analysis, suggests that at least 50-60% of the bacterial genera from the intestinal microbiota of a healthy individual produce resilient spores, specialized for host-to-host transmission. Our approach unlocks the human intestinal microbiota for phenotypic analysis and reveals how a marked proportion of oxygen-sensitive intestinal bacteria can be transmitted between individuals, affecting microbiota heritability.}, }
@article {pmid27143475, year = {2016}, author = {Gloor, GB and Wu, JR and Pawlowsky-Glahn, V and Egozcue, JJ}, title = {It's all relative: analyzing microbiome data as compositions.}, journal = {Annals of epidemiology}, volume = {26}, number = {5}, pages = {322-329}, doi = {10.1016/j.annepidem.2016.03.003}, pmid = {27143475}, issn = {1873-2585}, support = {//CIHR/Canada ; }, mesh = {Datasets as Topic ; Female ; High-Throughput Nucleotide Sequencing/*methods ; Humans ; Male ; Microbiota/*genetics ; RNA, Ribosomal, 16S/*genetics ; Sensitivity and Specificity ; }, abstract = {PURPOSE: The ability to properly analyze and interpret large microbiome data sets has lagged behind our ability to acquire such data sets from environmental or clinical samples. Sequencing instruments impose a structure on these data: the natural sample space of a 16S rRNA gene sequencing data set is a simplex, which is a part of real space that is restricted to nonnegative values with a constant sum. Such data are compositional and should be analyzed using compositionally appropriate tools and approaches. However, most of the tools for 16S rRNA gene sequencing analysis assume these data are unrestricted.<br><br>METHODS: We show that existing tools for compositional data (CoDa) analysis can be readily adapted to analyze high-throughput sequencing data sets.<br><br>RESULTS: The Human Microbiome Project tongue versus buccal mucosa data set shows how the CoDa approach can address the major elements of microbiome analysis. Reanalysis of a publicly available autism microbiome data set shows that the CoDa approach in concert with multiple hypothesis test corrections prevent false positive identifications.<br><br>CONCLUSIONS: The CoDa approach is readily scalable to microbiome-sized analyses. We provide example code and make recommendations to improve the analysis and reporting of microbiome data sets.}, }
@article {pmid27130534, year = {2016}, author = {Putignani, L and Dallapiccola, B}, title = {Foodomics as part of the host-microbiota-exposome interplay.}, journal = {Journal of proteomics}, volume = {147}, number = {}, pages = {3-20}, doi = {10.1016/j.jprot.2016.04.033}, pmid = {27130534}, issn = {1876-7737}, mesh = {Diet/*trends ; Gastrointestinal Microbiome ; Gene Expression Profiling/methods ; Humans ; Metabolomics/methods ; *Microbiota ; Nutritional Status ; Proteomics/methods ; Systems Biology/*methods ; }, abstract = {UNLABELLED: The functional complexity of human gut microbiota and its relationship with host physiology and environmental modulating factors, offers the opportunity to investigate (i) the host and microbiota role in organism-environment relationship; (ii) the individual functional diversity and response to environmental stimuli (exposome); (iii) the host genome and microbiota metagenomes' modifications by diet-mediated epigenomic controls (nutriepigenomics); and (iv) the genotype-phenotype "trajectories" under physiological and disease constraints. Systems biology-based approaches aim at integrating biological data at cellular, tissue and organ organization levels, using computational modeling to interpret diseases' physiopathological mechanisms (i.e., onset and progression). Proteomics improves the existing gene models by profiling molecular phenotypes at protein abundance level, by analyzing post-translational modifications and protein-protein interactions and providing specific pathway information, hence contributing to functional molecular networks. Transcriptomics and metabolomics may determine host ad microbiota changes induced by food ingredients at molecular level, complementing functional genomics and proteomics data. Since foodomics is an -omic wide methodology may feed back all integrative data to foster the omics-based systems medicine field. Hence, coupled to ecological genomics of gut microbial communities, foodomics may highlight health benefits from nutrients, dissecting diet-induced gut microbiota eubiosis mechanisms and significantly contributing to understand and prevent complex disease phenotypes.<br><br>BIOLOGICAL SIGNIFICANCE: Besides transcriptomics and proteomics there is a growing interest in applying metabolic profiling to food science for the development of functional foods. Indeed, one of the biggest challenges of modern nutrition is to propose a healthy diet to populations worldwide, intrinsically respecting the high inter-individual variability, driven by complex host/nutrients/microbiota/environment interactions. Therefore, metabolic profiling can assist at various levels for the development of functional foods, starting from screening for food composition to identification of new biomarkers to trace food intake. This current approach can support diet intervention strategies, epidemiological studies, and controlling of metabolic disorders worldwide spreading, hence ensuring healthy aging. With high-throughput molecular technologies driving foodomics, studying bidirectional interactions of host-microbial co-metabolism, innate immune development, dysfunctional nutrient absorption and processing, complex signaling pathways involved in nutritional metabolism, is now likely. In all cases, as microbiome pipeline efforts continue, it is possible that enhanced standardized protocols can be developed, which may lead to new testable biological and clinical hypotheses. This Review provides a comprehensive update on the current state-of-the-art of the integrated -omics route in food, microbiota and host co-metabolism studies, which may revolutionize the design of new dietary intervention strategies.}, }
@article {pmid27124399, year = {2016}, author = {Tandon, D and Haque, MM and Mande, SS}, title = {Inferring Intra-Community Microbial Interaction Patterns from Metagenomic Datasets Using Associative Rule Mining Techniques.}, journal = {PloS one}, volume = {11}, number = {4}, pages = {e0154493}, pmid = {27124399}, issn = {1932-6203}, mesh = {Algorithms ; Data Mining/*methods ; Databases, Genetic ; Gastrointestinal Microbiome ; Humans ; *Metagenome ; *Microbial Interactions ; Web Browser ; }, abstract = {The nature of inter-microbial metabolic interactions defines the stability of microbial communities residing in any ecological niche. Deciphering these interaction patterns is crucial for understanding the mode/mechanism(s) through which an individual microbial community transitions from one state to another (e.g. from a healthy to a diseased state). Statistical correlation techniques have been traditionally employed for mining microbial interaction patterns from taxonomic abundance data corresponding to a given microbial community. In spite of their efficiency, these correlation techniques can capture only 'pair-wise interactions'. Moreover, their emphasis on statistical significance can potentially result in missing out on several interactions that are relevant from a biological standpoint. This study explores the applicability of one of the earliest association rule mining algorithm i.e. the 'Apriori algorithm' for deriving 'microbial association rules' from the taxonomic profile of given microbial community. The classical Apriori approach derives association rules by analysing patterns of co-occurrence/co-exclusion between various '(subsets of) features/items' across various samples. Using real-world microbiome data, the efficiency/utility of this rule mining approach in deciphering multiple (biologically meaningful) association patterns between 'subsets/subgroups' of microbes (constituting microbiome samples) is demonstrated. As an example, association rules derived from publicly available gut microbiome datasets indicate an association between a group of microbes (Faecalibacterium, Dorea, and Blautia) that are known to have mutualistic metabolic associations among themselves. Application of the rule mining approach on gut microbiomes (sourced from the Human Microbiome Project) further indicated similar microbial association patterns in gut microbiomes irrespective of the gender of the subjects. A Linux implementation of the Association Rule Mining (ARM) software (customised for deriving 'microbial association rules' from microbiome data) is freely available for download from the following link: http://metagenomics.atc.tcs.com/arm.}, }
@article {pmid27123663, year = {2016}, author = {Wolf, PG and Biswas, A and Morales, SE and Greening, C and Gaskins, HR}, title = {H2 metabolism is widespread and diverse among human colonic microbes.}, journal = {Gut microbes}, volume = {7}, number = {3}, pages = {235-245}, pmid = {27123663}, issn = {1949-0984}, mesh = {Bacteria/*classification/*metabolism ; Carbohydrate Metabolism ; Colon/*microbiology ; Feces/microbiology ; Fermentation ; Healthy Volunteers ; Humans ; Hydrogen/*metabolism ; Hydrogenase/metabolism ; Metabolic Networks and Pathways ; }, abstract = {Microbial molecular hydrogen (H2) cycling is central to metabolic homeostasis and microbial composition in the human gastrointestinal tract. Molecular H2 is produced as an endproduct of carbohydrate fermentation and is reoxidised primarily by sulfate-reduction, acetogenesis, and methanogenesis. However, the enzymatic basis for these processes is incompletely understood and the hydrogenases responsible have not been investigated. In this work, we surveyed the genomic and metagenomic distribution of hydrogenase-encoding genes in the human colon to infer dominant mechanisms of H2 cycling. The data demonstrate that 70% of gastrointestinal microbial species listed in the Human Microbiome Project encode the genetic capacity to metabolise H2. A wide variety of anaerobically-adapted hydrogenases were present, with [FeFe]-hydrogenases predominant. We subsequently analyzed the hydrogenase gene content of stools from 20 healthy human subjects. The hydrogenase gene content of all samples was overwhelmingly dominated by fermentative and electron-bifurcating [FeFe]-hydrogenases emerging from the Bacteroidetes and Firmicutes. This study supports that H2 metabolism in the human gut is driven by fermentative H2 production and interspecies H2 transfer. However, it suggests that electron-bifurcation rather than respiration is the dominant mechanism of H2 reoxidation in the human colon, generating reduced ferredoxin to sustain carbon-fixation (e.g. acetogenesis) and respiration (via the Rnf complex). This work provides the first comprehensive bioinformatic insight into the mechanisms of H2 metabolism in the human colon.}, }
@article {pmid27122046, year = {2016}, author = {Lloyd-Price, J and Abu-Ali, G and Huttenhower, C}, title = {The healthy human microbiome.}, journal = {Genome medicine}, volume = {8}, number = {1}, pages = {51}, pmid = {27122046}, issn = {1756-994X}, mesh = {Bacteria/*classification/*genetics ; Genetic Variation ; Healthy Volunteers ; Humans ; Metagenome ; *Microbiota ; Phylogeny ; Phylogeography ; }, abstract = {Humans are virtually identical in their genetic makeup, yet the small differences in our DNA give rise to tremendous phenotypic diversity across the human population. By contrast, the metagenome of the human microbiome-the total DNA content of microbes inhabiting our bodies-is quite a bit more variable, with only a third of its constituent genes found in a majority of healthy individuals. Understanding this variability in the "healthy microbiome" has thus been a major challenge in microbiome research, dating back at least to the 1960s, continuing through the Human Microbiome Project and beyond. Cataloguing the necessary and sufficient sets of microbiome features that support health, and the normal ranges of these features in healthy populations, is an essential first step to identifying and correcting microbial configurations that are implicated in disease. Toward this goal, several population-scale studies have documented the ranges and diversity of both taxonomic compositions and functional potentials normally observed in the microbiomes of healthy populations, along with possible driving factors such as geography, diet, and lifestyle. Here, we review several definitions of a 'healthy microbiome' that have emerged, the current understanding of the ranges of healthy microbial diversity, and gaps such as the characterization of molecular function and the development of ecological therapies to be addressed in the future.}, }
@article {pmid27121424, year = {2016}, author = {Logan, AC and Jacka, FN and Craig, JM and Prescott, SL}, title = {The Microbiome and Mental Health: Looking Back, Moving Forward with Lessons from Allergic Diseases.}, journal = {Clinical psychopharmacology and neuroscience : the official scientific journal of the Korean College of Neuropsychopharmacology}, volume = {14}, number = {2}, pages = {131-147}, pmid = {27121424}, issn = {1738-1088}, abstract = {Relationships between gastrointestinal viscera and human emotions have been documented by virtually all medical traditions known to date. The focus on this relationship has waxed and waned through the centuries, with noted surges in interest driven by cultural forces. Here we explore some of this history and the emerging trends in experimental and clinical research. In particular, we pay specific attention to how the hygiene hypothesis and emerging research on traditional dietary patterns has helped re-ignite interest in the use of microbes to support mental health. At present, the application of microbes and their structural parts as a means to positively influence mental health is an area filled with promise. However, there are many limitations within this new paradigm shift in neuropsychiatry. Impediments that could block translation of encouraging experimental studies include environmental forces that work toward dysbiosis, perhaps none more important than westernized dietary patterns. On the other hand, it is likely that specific dietary choices may amplify the value of future microbial-based therapeutics. Pre-clinical and clinical research involving microbiota and allergic disorders has predated recent work in psychiatry, an early start that provides valuable lessons. The microbiome is intimately connected to diet, nutrition, and other lifestyle variables; microbial-based psychopharmacology will need to consider this contextual application, otherwise the ceiling of clinical expectations will likely need to be lowered.}, }
@article {pmid27121074, year = {2017}, author = {Verma, M}, title = {Mechanistic and Technical Challenges in Studying the Human Microbiome and Cancer Epidemiology.}, journal = {Technology in cancer research &amp; treatment}, volume = {16}, number = {2}, pages = {150-158}, pmid = {27121074}, issn = {1533-0338}, mesh = {Data Mining ; Digestive System Neoplasms/epidemiology/etiology ; Humans ; Metagenomics/methods ; Microbiological Techniques ; *Microbiota ; Neoplasms/*epidemiology/*etiology ; Research Design ; }, abstract = {This article reviews the significance of the microbiome in cancer epidemiology, mechanistic and technical challenges in the field, and characterization of the microbiome in different tumor types to identify biomarkers of risk, progression, and prognosis. Publications on the microbiome and cancer epidemiology were reviewed to analyze sample collection and processing, microbiome taxa characterization by 16S ribosomal RNA sequencing, and microbiome metabolite characterization (metabotyping) by nuclear magnetic resonance and mass spectrometry. The analysis identified methodology types, research design, sample types, and issues in integrating data from different platforms. Aerodigestive cancer epidemiology studies conducted by different groups demonstrated the significance of microbiome information in developing approaches to improve health. Challenges exist in sample preparation and processing (eg, standardization of methods for collection and analysis). These challenges relate to technology, data integration from "omics" studies, inherent bias in primer selection during 16S ribosomal RNA sequencing, the need for large consortia with well-characterized biospecimens, cause and effect issues, resilience of microbiota to exposure events (requires longitudinal studies), and expanding studies for fungal and viral diversity (most studies used bacterial 16S ribosomal RNA sequencing for microbiota characterization). Despite these challenges, microbiome and cancer epidemiology studies are significant and may facilitate cancer risk assessment, diagnosis, and prognosis. In the future, clinical trials likely will use microbiota modifications to improve the efficacy of existing treatments.}, }
@article {pmid27120414, year = {2016}, author = {Dar, D and Shamir, M and Mellin, JR and Koutero, M and Stern-Ginossar, N and Cossart, P and Sorek, R}, title = {Term-seq reveals abundant ribo-regulation of antibiotics resistance in bacteria.}, journal = {Science (New York, N.Y.)}, volume = {352}, number = {6282}, pages = {aad9822}, pmid = {27120414}, issn = {1095-9203}, support = {260432/ERC_/European Research Council/International ; 670823/ERC_/European Research Council/International ; }, mesh = {3' Untranslated Regions/genetics ; Anti-Bacterial Agents/pharmacology ; Bacillus subtilis/drug effects/genetics ; Drug Resistance, Bacterial/*genetics ; Enterococcus faecalis/drug effects ; Gastrointestinal Microbiome/drug effects/genetics ; *Gene Expression Regulation, Bacterial ; Genome, Bacterial/genetics ; Genome-Wide Association Study/*methods ; High-Throughput Nucleotide Sequencing/*methods ; Humans ; Listeria monocytogenes/drug effects/genetics ; Ribosomes/metabolism ; Riboswitch/*genetics ; Sequence Analysis, RNA/methods ; *Transcription Termination, Genetic ; }, abstract = {Riboswitches and attenuators are cis-regulatory RNA elements, most of which control bacterial gene expression via metabolite-mediated, premature transcription termination. We developed an unbiased experimental approach for genome-wide discovery of such ribo-regulators in bacteria. We also devised an experimental platform that quantitatively measures the in vivo activity of all such regulators in parallel and enables rapid screening for ribo-regulators that respond to metabolites of choice. Using this approach, we detected numerous antibiotic-responsive ribo-regulators that control antibiotic resistance genes in pathogens and in the human microbiome. Studying one such regulator in Listeria monocytogenes revealed an attenuation mechanism mediated by antibiotic-stalled ribosomes. Our results expose broad roles for conditional termination in regulating antibiotic resistance and provide a tool for discovering riboswitches and attenuators that respond to previously unknown ligands.}, }
@article {pmid27115907, year = {2017}, author = {Ipci, K and Altıntoprak, N and Muluk, NB and Senturk, M and Cingi, C}, title = {The possible mechanisms of the human microbiome in allergic diseases.}, journal = {European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery}, volume = {274}, number = {2}, pages = {617-626}, pmid = {27115907}, issn = {1434-4726}, mesh = {Dysbiosis/*immunology ; Humans ; Hypersensitivity/*microbiology ; Immune System/*microbiology ; Intestines/immunology/microbiology ; Microbiota/*immunology ; }, abstract = {In the present paper, we discuss the importance of the microbiome in allergic disease. In this review paper, the data from the Medline (PubMed) and search engine of Kirikkale University were systematically searched for all relevant articles in June 15th, 2015 for the past 30 years. The keywords of "microbiome", "dysbiosis", "allergy", "allergic rhinitis", "allergic disease", "mechanisms" and "treatment" were used alone or together. In this paper, microbiomes were presented in terms of "Definition", "Influence of \the human microbiome on health", "The microbiome and allergic diseases", and "Modulation of the gut microbiota in terms of treatment and prevention". Microbiological dysbiosis is also reviewed. The microbiome is the genetic material of all microbes (bacteria, fungi, protozoa, and viruses) that live on or in the human body. Microbes outnumber human cells in a 10:1 ratio. Most microbes live in the gut, particularly the large intestine. Changes in the immune function of the respiratory tract are (at least in theory) linked to the immunomodulatory activity of the gut microbiota via the concept of a "common mucosal response". The gut microbiota shapes systemic immunity, thus affecting the lung mucosa. Alternatively, changes in the gut microbiota may reflect alterations in the oropharyngeal microbiota, which may in turn directly affect the lung microbiota and host immune responses via microaspiration. Dysbiosis is defined as qualitative and quantitative changes in the intestinal flora; and modern diet and lifestyle, antibiotics, psychological and physical stress result in alterations in bacterial metabolism, as well as the overgrowth of potentially pathogenic microorganisms. All immune system components are directly or indirectly regulated by the microbiota. The nature of microbial exposure early in life appears to be important for the development of robust immune regulation; disruption of either the microbiota or the host response can trigger chronic inflammation. Dysbiosis is also an important clinical entity. Antibiotics, psychological and physical stress, and dietary factors contribute to intestinal dysbiosis.}, }
@article {pmid27110483, year = {2016}, author = {Heiman, ML and Greenway, FL}, title = {A healthy gastrointestinal microbiome is dependent on dietary diversity.}, journal = {Molecular metabolism}, volume = {5}, number = {5}, pages = {317-320}, pmid = {27110483}, issn = {2212-8778}, abstract = {BACKGROUND: Like all healthy ecosystems, richness of microbiota species characterizes the GI microbiome in healthy individuals. Conversely, a loss in species diversity is a common finding in several disease states. This biome is flooded with energy in the form of undigested and partially digested foods, and in some cases drugs and dietary supplements. Each microbiotic species in the biome transforms that energy into new molecules, which may signal messages to physiological systems of the host.<br><br>SCOPE OF REVIEW: Dietary choices select substrates for species, providing a competitive advantage over other GI microbiota. The more diverse the diet, the more diverse the microbiome and the more adaptable it will be to perturbations. Unfortunately, dietary diversity has been lost during the past 50 years and dietary choices that exclude food products from animals or plants will narrow the GI microbiome further.<br><br>MAJOR CONCLUSION: Additional research into expanding gut microbial richness by dietary diversity is likely to expand concepts in healthy nutrition, stimulate discovery of new diagnostics, and open up novel therapeutic possibilities.}, }
@article {pmid27107961, year = {2016}, author = {Dols, JA and Molenaar, D and van der Helm, JJ and Caspers, MP and de Kat Angelino-Bart, A and Schuren, FH and Speksnijder, AG and Westerhoff, HV and Richardus, JH and Boon, ME and Reid, G and de Vries, HJ and Kort, R}, title = {Molecular assessment of bacterial vaginosis by Lactobacillus abundance and species diversity.}, journal = {BMC infectious diseases}, volume = {16}, number = {}, pages = {180}, pmid = {27107961}, issn = {1471-2334}, support = {BB/I004688/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; BB/I004696/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; BB/F003544/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; BB/F003552/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; BB/D019079/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; BB/F003528/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; BB/C008219/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; BB/I00470X/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; BB/F003536/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Adolescent ; Adult ; Bacteria/classification/*genetics/isolation &amp; purification ; Cluster Analysis ; DNA, Bacterial/isolation &amp; purification/metabolism ; Female ; Gardnerella vaginalis/genetics/isolation &amp; purification ; Humans ; Lactobacillus/genetics/isolation &amp; purification ; Microbiota ; Middle Aged ; Oligonucleotide Array Sequence Analysis ; Polymerase Chain Reaction ; RNA, Ribosomal, 16S/analysis/genetics/metabolism ; Sequence Analysis, DNA ; Species Specificity ; Vaginosis, Bacterial/*diagnosis/microbiology ; Vigna/microbiology ; Young Adult ; }, abstract = {BACKGROUND: To date, women are most often diagnosed with bacterial vaginosis (BV) using microscopy based Nugent scoring or Amsel criteria. However, the accuracy is less than optimal. The aim of the present study was to confirm the identity of known BV-associated composition profiles and evaluate indicators for BV using three molecular methods.<br><br>METHODS: Evaluation of indicators for BV was carried out by 16S rRNA amplicon sequencing of the V5-V7 region, a tailor-made 16S rRNA oligonucleotide-based microarray, and a PCR-based profiling technique termed IS-profiling, which is based on fragment variability of the 16S-23S rRNA intergenic spacer region. An inventory of vaginal bacterial species was obtained from 40 females attending a Dutch sexually transmitted infection outpatient clinic, of which 20 diagnosed with BV (Nugent score 7-10), and 20 BV negative (Nugent score 0-3).<br><br>RESULTS: Analysis of the bacterial communities by 16S rRNA amplicon sequencing revealed two clusters in the BV negative women, dominated by either Lactobacillus iners or Lactobacillus crispatus and three distinct clusters in the BV positive women. In the former, there was a virtually complete, negative correlation between L. crispatus and L. iners. BV positive subjects showed cluster profiles that were relatively high in bacterial species diversity and dominated by anaerobic species, including Gardnerella vaginalis, and those belonging to the Families of Lachnospiraceae and Leptotrichiaceae. Accordingly, the Gini-Simpson index of species diversity, and the relative abundance Lactobacillus species appeared consistent indicators for BV. Under the conditions used, only the 16S rRNA amplicon sequencing method was suitable to assess species diversity, while all three molecular composition profiling methods were able to indicate Lactobacillus abundance in the vaginal microbiota.<br><br>CONCLUSION: An affordable and simple molecular test showing a depletion of the genus Lactobacillus in combination with an increased species diversity of vaginal microbiota could serve as an alternative and practical diagnostic method for the assessment of BV.}, }
@article {pmid27102203, year = {2016}, author = {Grassl, N and Kulak, NA and Pichler, G and Geyer, PE and Jung, J and Schubert, S and Sinitcyn, P and Cox, J and Mann, M}, title = {Ultra-deep and quantitative saliva proteome reveals dynamics of the oral microbiome.}, journal = {Genome medicine}, volume = {8}, number = {1}, pages = {44}, pmid = {27102203}, issn = {1756-994X}, mesh = {Adult ; Bacteria/classification/genetics/metabolism ; Bacterial Proteins ; Biodiversity ; Chromatography, Liquid ; Female ; Humans ; Male ; Mass Spectrometry ; Metagenome ; Metagenomics ; *Microbiota ; Mouth/*microbiology ; Peptides/metabolism ; Phylogeny ; *Proteome ; *Proteomics/methods ; Saliva/*metabolism ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization ; Young Adult ; }, abstract = {BACKGROUND: The oral cavity is home to one of the most diverse microbial communities of the human body and a major entry portal for pathogens. Its homeostasis is maintained by saliva, which fulfills key functions including lubrication of food, pre-digestion, and bacterial defense. Consequently, disruptions in saliva secretion and changes in the oral microbiome contribute to conditions such as tooth decay and respiratory tract infections. Here we set out to quantitatively map the saliva proteome in great depth with a rapid and in-depth mass spectrometry-based proteomics workflow.<br><br>METHODS: We used recent improvements in mass spectrometry (MS)-based proteomics to develop a rapid workflow for mapping the saliva proteome quantitatively and at great depth. Standard clinical cotton swabs were used to collect saliva form eight healthy individuals at two different time points, allowing us to study inter-individual differences and interday changes of the saliva proteome. To accurately identify microbial proteins, we developed a method called "split by taxonomy id" that prevents peptides shared by humans and bacteria or between different bacterial phyla to contribute to protein identification.<br><br>RESULTS: Microgram protein amounts retrieved from cotton swabs resulted in more than 3700 quantified human proteins in 100-min gradients or 5500 proteins after simple fractionation. Remarkably, our measurements also quantified more than 2000 microbial proteins from 50 bacterial genera. Co-analysis of the proteomics results with next-generation sequencing data from the Human Microbiome Project as well as a comparison to MALDI-TOF mass spectrometry on microbial cultures revealed strong agreement. The oral microbiome differs between individuals and changes drastically upon eating and tooth brushing.<br><br>CONCLUSION: Rapid shotgun and robust technology can now simultaneously characterize the human and microbiome contributions to the proteome of a body fluid and is therefore a valuable complement to genomic studies. This opens new frontiers for the study of host-pathogen interactions and clinical saliva diagnostics.}, }
@article {pmid27102132, year = {2016}, author = {Josephs-Spaulding, J and Beeler, E and Singh, OV}, title = {Human microbiome versus food-borne pathogens: friend or foe.}, journal = {Applied microbiology and biotechnology}, volume = {100}, number = {11}, pages = {4845-4863}, doi = {10.1007/s00253-016-7523-7}, pmid = {27102132}, issn = {1432-0614}, mesh = {Diet ; Fermentation ; Foodborne Diseases/*microbiology/*therapy ; Humans ; Metagenomics ; *Microbiota ; Multilocus Sequence Typing ; Probiotics ; Symbiosis ; }, abstract = {As food safety advances, there is a great need to maintain, distribute, and provide high-quality food to a much broader consumer base. There is also an ever-growing "arms race" between pathogens and humans as food manufacturers. The human microbiome is a collective organ of microbes that have found community niches while associating with their host and other microorganisms. Humans play an important role in modifying the environment of these organisms through their life choices, especially through individual diet. The composition of an individual's diet influences the digestive system-an ecosystem with the greatest number and largest diversity of organisms currently known. Organisms living on and within food have the potential to be either friends or foes to the consumer. Maintenance of this system can have multiple benefits, but lack of maintenance can lead to a host of chronic and preventable diseases. Overall, this dynamic system is influenced by intense competition from food-borne pathogens, lifestyle, overall diet, and presiding host-associated microbiota.}, }
@article {pmid28721243, year = {2016}, author = {Nguyen, NP and Warnow, T and Pop, M and White, B}, title = {A perspective on 16S rRNA operational taxonomic unit clustering using sequence similarity.}, journal = {NPJ biofilms and microbiomes}, volume = {2}, number = {}, pages = {16004}, pmid = {28721243}, issn = {2055-5008}, abstract = {The standard pipeline for 16S amplicon analysis starts by clustering sequences within a percent sequence similarity threshold (typically 97%) into 'Operational Taxonomic Units' (OTUs). From each OTU, a single sequence is selected as a representative. This representative sequence is annotated, and that annotation is applied to all remaining sequences within that OTU. This perspective paper will discuss the known shortcomings of this standard approach using results obtained from the Human Microbiome Project. In particular, we will show that the traditional approach of using pairwise sequence alignments to compute sequence similarity can result in poorly clustered OTUs. As OTUs are typically annotated based upon a single representative sequence, poorly clustered OTUs can have significant impact on downstream analyses. These results suggest that we need to move beyond simple clustering techniques for 16S analysis.}, }
@article {pmid27081642, year = {2016}, author = {Pevsner-Fischer, M and Tuganbaev, T and Meijer, M and Zhang, SH and Zeng, ZR and Chen, MH and Elinav, E}, title = {Role of the microbiome in non-gastrointestinal cancers.}, journal = {World journal of clinical oncology}, volume = {7}, number = {2}, pages = {200-213}, pmid = {27081642}, issn = {2218-4333}, abstract = {"The forgotten organ", the human microbiome, comprises a community of microorganisms that colonizes various sites of the human body. Through coevolution of bacteria, archaea and fungi with the human host over thousands of years, a complex host-microbiome relationship emerged in which many functions, including metabolism and immune responses, became codependent. This coupling becomes evident when disruption in the microbiome composition, termed dysbiosis, is mirrored by the development of pathologies in the host. Among the most serious consequences of dysbiosis, is the development of cancer. As many as 20% of total cancers worldwide are caused by a microbial agent. To date, a vast majority of microbiome-cancer studies focus solely on the microbiome of the large intestine and the development of gastrointestinal cancers. Here, we will review the available evidence implicating microbiome involvement in the development and progression of non-gastrointestinal cancers, while distinguishing between viral and bacterial drivers of cancer, as well as "local" and "systemic", "cancer-stimulating" and "cancer-suppressing" effects of the microbiome. Developing a system-wide approach to cancer-microbiome studies will be crucial in understanding how microbiome influences carcinogenesis, and may enable to employ microbiome-targeting approaches as part of cancer treatment.}, }
@article {pmid27074706, year = {2016}, author = {Langdon, A and Crook, N and Dantas, G}, title = {The effects of antibiotics on the microbiome throughout development and alternative approaches for therapeutic modulation.}, journal = {Genome medicine}, volume = {8}, number = {1}, pages = {39}, pmid = {27074706}, issn = {1756-994X}, support = {DP2 DK098089/DK/NIDDK NIH HHS/United States ; R01 GM099538/GM/NIGMS NIH HHS/United States ; T32 DK077653/DK/NIDDK NIH HHS/United States ; DP2-DK-098089/DK/NIDDK NIH HHS/United States ; R01-GM099538/GM/NIGMS NIH HHS/United States ; UL1 TR000448/TR/NCATS NIH HHS/United States ; TL1 TR000449/TR/NCATS NIH HHS/United States ; }, mesh = {Anti-Bacterial Agents/adverse effects/*pharmacology/*therapeutic use ; Bacterial Infections/*drug therapy/*microbiology ; Disease Susceptibility ; Host-Pathogen Interactions/drug effects ; Humans ; Metagenome ; Metagenomics ; Microbiota/*drug effects ; Risk Factors ; }, abstract = {The widespread use of antibiotics in the past 80 years has saved millions of human lives, facilitated technological progress and killed incalculable numbers of microbes, both pathogenic and commensal. Human-associated microbes perform an array of important functions, and we are now just beginning to understand the ways in which antibiotics have reshaped their ecology and the functional consequences of these changes. Mounting evidence shows that antibiotics influence the function of the immune system, our ability to resist infection, and our capacity for processing food. Therefore, it is now more important than ever to revisit how we use antibiotics. This review summarizes current research on the short-term and long-term consequences of antibiotic use on the human microbiome, from early life to adulthood, and its effect on diseases such as malnutrition, obesity, diabetes, and Clostridium difficile infection. Motivated by the consequences of inappropriate antibiotic use, we explore recent progress in the development of antivirulence approaches for resisting infection while minimizing resistance to therapy. We close the article by discussing probiotics and fecal microbiota transplants, which promise to restore the microbiota after damage of the microbiome. Together, the results of studies in this field emphasize the importance of developing a mechanistic understanding of gut ecology to enable the development of new therapeutic strategies and to rationally limit the use of antibiotic compounds.}, }
@article {pmid27068172, year = {2016}, author = {Snider, EJ and Freedberg, DE and Abrams, JA}, title = {Potential Role of the Microbiome in Barrett's Esophagus and Esophageal Adenocarcinoma.}, journal = {Digestive diseases and sciences}, volume = {61}, number = {8}, pages = {2217-2225}, pmid = {27068172}, issn = {1573-2568}, support = {KL2 TR000081/TR/NCATS NIH HHS/United States ; U54 CA163004/CA/NCI NIH HHS/United States ; }, mesh = {Adenocarcinoma/epidemiology/*microbiology ; Barrett Esophagus/epidemiology/*microbiology ; Dysbiosis/epidemiology/*microbiology ; Esophageal Neoplasms/epidemiology/*microbiology ; Esophagitis, Peptic/epidemiology/*microbiology ; Esophagus/*microbiology ; Gastroesophageal Reflux/epidemiology/microbiology ; Humans ; *Microbiota ; Obesity/epidemiology/microbiology ; Precancerous Conditions/epidemiology/*microbiology ; Risk Factors ; }, abstract = {Esophageal adenocarcinoma and its precursor Barrett's esophagus have been rapidly increasing in incidence for half a century, for reasons not adequately explained by currently identified risk factors such as gastroesophageal reflux disease and obesity. The upper gastrointestinal microbiome may represent another potential cofactor. The distal esophagus has a distinct microbiome of predominantly oral-derived flora, which is altered in Barrett's esophagus and reflux esophagitis. Chronic low-grade inflammation or direct carcinogenesis from this altered microbiome may combine with known risk factors to promote Barrett's metaplasia and progression to adenocarcinoma.}, }
@article {pmid27062925, year = {2016}, author = {Xu, Q and Shoji, M and Shibata, S and Naito, M and Sato, K and Elsliger, MA and Grant, JC and Axelrod, HL and Chiu, HJ and Farr, CL and Jaroszewski, L and Knuth, MW and Deacon, AM and Godzik, A and Lesley, SA and Curtis, MA and Nakayama, K and Wilson, IA}, title = {A Distinct Type of Pilus from the Human Microbiome.}, journal = {Cell}, volume = {165}, number = {3}, pages = {690-703}, pmid = {27062925}, issn = {1097-4172}, support = {P41 GM103393/GM/NIGMS NIH HHS/United States ; U54 GM094586/GM/NIGMS NIH HHS/United States ; }, mesh = {Amino Acid Sequence ; Crystallography, X-Ray ; Fimbriae Proteins/*chemistry/genetics/metabolism ; *Fimbriae, Bacterial ; *Gastrointestinal Microbiome ; Humans ; Lipoproteins/chemistry/metabolism ; Models, Molecular ; Molecular Sequence Data ; Sequence Alignment ; }, abstract = {Pili are proteinaceous polymers of linked pilins that protrude from the cell surface of many bacteria and often mediate adherence and virulence. We investigated a set of 20 Bacteroidia pilins from the human microbiome whose structures and mechanism of assembly were unknown. Crystal structures and biochemical data revealed a diverse protein superfamily with a common Greek-key β sandwich fold with two transthyretin-like repeats that polymerize into a pilus through a strand-exchange mechanism. The assembly mechanism of the central, structural pilins involves proteinase-assisted removal of their N-terminal β strand, creating an extended hydrophobic groove that binds the C-terminal donor strands of the incoming pilin. Accessory pilins at the tip and base have unique structural features specific to their location, allowing initiation or termination of the assembly. The Bacteroidia pilus, therefore, has a biogenesis mechanism that is distinct from other known pili and likely represents a different type of bacterial pilus.}, }
@article {pmid27059297, year = {2016}, author = {Greenhalgh, K and Meyer, KM and Aagaard, KM and Wilmes, P}, title = {The human gut microbiome in health: establishment and resilience of microbiota over a lifetime.}, journal = {Environmental microbiology}, volume = {18}, number = {7}, pages = {2103-2116}, pmid = {27059297}, issn = {1462-2920}, support = {R01 NR014792/NR/NINR NIH HHS/United States ; }, mesh = {Animals ; Bacteria/classification/genetics/*isolation &amp; purification ; *Gastrointestinal Microbiome ; Gastrointestinal Tract/microbiology ; Health ; Humans ; Metagenomics ; }, abstract = {With technological advances in culture-independent molecular methods, we are uncovering a new facet of our natural history by accounting for the vast diversity of microbial life which colonizes the human body. The human microbiome contributes functional genes and metabolites which affect human physiology and are, therefore, considered an important factor for maintaining health. Much has been described in the past decade based primarily on 16S rRNA gene amplicon sequencing regarding the diversity, structure, stability and dynamics of human microbiota in their various body habitats, most notably within the gastrointestinal tract (GIT). Relatively high levels of variation have been described across different stages of life and geographical locations for the GIT microbiome. These observations may prove helpful for the future contextualization of patterns in other body habitats especially in relation to identifying generalizable trends over human lifetime. Given the large degree of complexity and variability, a key challenge will be how to define baseline healthy microbiomes and how to identify features which reflect deviations therefrom in the future. In this context, metagenomics and functional omics will likely play a central role as they will allow resolution of microbiome-conferred functionalities associated with health. Such information will be vital for formulating therapeutic interventions aimed at managing microbiota-mediated health particularly in the GIT over the course of a human lifetime.}, }
@article {pmid27051943, year = {2015}, author = {Xin, X and Junzhi, H and Xuedong, Z}, title = {[Oral microbiota: a promising predictor of human oral and systemic diseases].}, journal = {Hua xi kou qiang yi xue za zhi = Huaxi kouqiang yixue zazhi = West China journal of stomatology}, volume = {33}, number = {6}, pages = {555-560}, pmid = {27051943}, issn = {1000-1182}, mesh = {*Biomarkers ; Cardiovascular Diseases/microbiology ; Dental Caries/microbiology ; Diabetes Mellitus/microbiology ; Humans ; Metagenomics ; *Microbiota ; Mouth/*microbiology ; Mouth Diseases/microbiology ; Neoplasms/microbiology ; Oral Health ; Periodontal Diseases/microbiology ; }, abstract = {A human oral microbiota is the ecological community of commensal, symbiotic, and pathogenic microorganisms found in human oral cavity. Oral microbiota exists mostly in the form of a biofilm and maintains a dynamic ecological equilibrium with the host body. However, the disturbance of this ecological balance inevitably causes oral infectious diseases, such as dental caries, apical periodontitis, periodontal diseases, pericoronitis, and craniofacial bone osteomyelitis. Oral microbiota is also correlated with many systemic diseases, including cancer, diabetes mellitus, rheumatoid arthritis, cardiovascular diseases, and preterm birth. Hence, oral microbiota has been considered as a potential biomarker of human diseases. The "Human Microbiome Project" and other metagenomic projects worldwide have advanced our knowledge of the human oral microbiota. The integration of these metadata has been the frontier of oral microbiology to improve clinical translation. By reviewing recent progress on studies involving oral microbiota-related oral and systemic diseases, we aimed to propose the essential role of oral microbiota in the prediction of the onset, progression, and prognosis of oral and systemic diseases. An oral microbiota-based prediction model helps develop a new paradigm of personalized medicine and benefits the human health in the post-metagenomics era.}, }
@article {pmid27050865, year = {2016}, author = {Broeckx, G and Vandenheuvel, D and Claes, IJ and Lebeer, S and Kiekens, F}, title = {Drying techniques of probiotic bacteria as an important step towards the development of novel pharmabiotics.}, journal = {International journal of pharmaceutics}, volume = {505}, number = {1-2}, pages = {303-318}, doi = {10.1016/j.ijpharm.2016.04.002}, pmid = {27050865}, issn = {1873-3476}, mesh = {Chemistry, Pharmaceutical/*methods ; Freeze Drying ; Humans ; Lorazepam ; *Microbial Viability ; Microbiota ; Probiotics/*administration &amp; dosage/chemistry ; Time Factors ; }, abstract = {The increasing knowledge about the human microbiome leads to the awareness of how important probiotics can be for our health. Although further substantiation is required, it appears that several pathologies could be treated or prevented by the administration of pharmaceutical formulations containing such live health-beneficial bacteria. These pharmabiotics need to provide their effects until the end of shelf life, which can be optimally achieved by drying them before further formulation. However, drying processes, including spray-, freeze-, vacuum- and fluidized bed drying, induce stress on probiotics, thus decreasing their viability. Several protection strategies can be envisaged to enhance their viability, including addition of protective agents, controlling the process parameters and prestressing the probiotics prior to drying. Moreover, probiotic viability needs to be maintained during long-term storage. Overall, lower storage temperature and low moisture content result in good survival rates. Attention should also be given to the rehydration conditions of the dried probiotics, as this can exert an important effect on their revival. By describing not only the characteristics, but also the viability results obtained by the most relevant drying techniques in the probiotic industry, we hope to facilitate the deliberate choice of drying process and protection strategy for specific probiotic and pharmabiotic applications.}, }
@article {pmid27048893, year = {2016}, author = {Reid, G}, title = {Probiotics: definition, scope and mechanisms of action.}, journal = {Best practice &amp; research. Clinical gastroenterology}, volume = {30}, number = {1}, pages = {17-25}, doi = {10.1016/j.bpg.2015.12.001}, pmid = {27048893}, issn = {1532-1916}, mesh = {Gastrointestinal Microbiome/*physiology ; Gastrointestinal Tract/*microbiology ; Guidelines as Topic ; Humans ; *Probiotics ; *Terminology as Topic ; }, abstract = {For a subject area of science, medicine and commerce to be so recently defined and investigated, few can compare to probiotics for the controversy they have incited. Barely a paper is published without the use of a different definition, or challenging the most used one, or proposing a different nuance of it. The situation has become even more surreal with the European Food and Safety Authority banning the word probiotic for use on labels. The reiteration of the FAO/WHO definition by the world's leading group of probiotic experts, should provide relative consistency in the near future, but what are the causes of these aberrations? This review will discuss the rationale for the definition, and the scope of the subject area and why alternatives emerge. While mechanisms of action are not widely proven, in vitro and some in vivo experiments support several. Ultimately, the goal of any field or product is to be understood by lay people and experts alike. Probiotics have come a long way in 100 years since Metchnikoff and 10 years since their globalization, but their evolution is far from over.}, }
@article {pmid27047589, year = {2016}, author = {Debelius, JW and Vázquez-Baeza, Y and McDonald, D and Xu, Z and Wolfe, E and Knight, R}, title = {Turning Participatory Microbiome Research into Usable Data: Lessons from the American Gut Project.}, journal = {Journal of microbiology &amp; biology education}, volume = {17}, number = {1}, pages = {46-50}, pmid = {27047589}, issn = {1935-7877}, abstract = {The role of the human microbiome is the subject of continued investigation resulting in increased understanding. However, current microbiome research has only scratched the surface of the variety of healthy microbiomes. Public participation in science through crowdsourcing and crowdfunding microbiome research provides a novel opportunity for both participants and investigators. However, turning participatory science into publishable data can be challenging. Clear communication with the participant base and among researchers can ameliorate some challenges. Three major aspects need to be considered: recruitment and ongoing interaction, sample collection, and data analysis. Usable data can be maximized through diligent participant interaction, careful survey design, and maintaining an open source pipeline. While participatory science will complement rather than replace traditional avenues, it presents new opportunities for studies in the microbiome and beyond.}, }
@article {pmid27039047, year = {2016}, author = {Fu, BC and Randolph, TW and Lim, U and Monroe, KR and Cheng, I and Wilkens, LR and Le Marchand, L and Hullar, MA and Lampe, JW}, title = {Characterization of the gut microbiome in epidemiologic studies: the multiethnic cohort experience.}, journal = {Annals of epidemiology}, volume = {26}, number = {5}, pages = {373-379}, pmid = {27039047}, issn = {1873-2585}, support = {P30 CA023108/CA/NCI NIH HHS/United States ; T32 CA009168/CA/NCI NIH HHS/United States ; P30 CA071789/CA/NCI NIH HHS/United States ; U01 CA164973/CA/NCI NIH HHS/United States ; P01 CA168530/CA/NCI NIH HHS/United States ; }, mesh = {Bacteria/classification ; *Epidemiologic Studies ; Ethnicity/*genetics ; Female ; Gastrointestinal Microbiome/*genetics/physiology ; Humans ; Male ; *Quality Control ; Real-Time Polymerase Chain Reaction/methods ; Research Design ; Sampling Studies ; Specimen Handling ; }, abstract = {PURPOSE: The development of next-generation sequencing and accompanying bioinformatics tools has revolutionized characterization of microbial communities. As interest grows in the role of the human microbiome in health and disease, so does the need for well-powered, robustly designed epidemiologic studies. Here, we discuss sources of bias that can arise in gut microbiome research.<br><br>METHODS: Research comparing methods of specimen collection, preservation, processing, and analysis of gut microbiome samples is reviewed. Although selected studies are primarily based on the gut, many of the same principles are applicable to samples derived from other anatomical sites. Methods for participant recruitment and sampling of the gut microbiome implemented in an ongoing population-based study, the Multiethnic Cohort (MEC), are also described.<br><br>RESULTS: Variation in methodologies can influence the results of human microbiome studies. To help minimize bias, techniques such as sample homogenization, addition of internal standards, and quality filtering should be adopted in protocols. Within the MEC, participant response rates to stool sample collection were comparable to other studies, and in-home stool sample collection yields sufficient high-quality DNA for gut microbiome analysis.<br><br>CONCLUSIONS: Application of standardized and quality controlled methods in human microbiome studies is necessary to ensure data quality and comparability among studies.}, }
@article {pmid27032825, year = {2016}, author = {Sun, X and Fiala, JL and Lowery, D}, title = {Patent watch: Modulating the human microbiome with live biotherapeutic products: intellectual property landscape.}, journal = {Nature reviews. Drug discovery}, volume = {15}, number = {4}, pages = {224-225}, doi = {10.1038/nrd.2016.48}, pmid = {27032825}, issn = {1474-1784}, mesh = {*Biological Therapy/methods/standards/trends ; Dysbiosis/microbiology/*therapy ; Humans ; *Intellectual Property ; Legislation, Medical ; *Microbiota ; Patents as Topic ; }, }
@article {pmid27028797, year = {2017}, author = {Del Chierico, F and Nobili, V and Vernocchi, P and Russo, A and De Stefanis, C and Gnani, D and Furlanello, C and Zandonà, A and Paci, P and Capuani, G and Dallapiccola, B and Miccheli, A and Alisi, A and Putignani, L}, title = {Gut microbiota profiling of pediatric nonalcoholic fatty liver disease and obese patients unveiled by an integrated meta-omics-based approach.}, journal = {Hepatology (Baltimore, Md.)}, volume = {65}, number = {2}, pages = {451-464}, doi = {10.1002/hep.28572}, pmid = {27028797}, issn = {1527-3350}, mesh = {Adolescent ; Analysis of Variance ; Case-Control Studies ; Child ; Fatty Liver/microbiology/physiopathology ; Female ; Gastrointestinal Microbiome/*genetics ; Humans ; Male ; Multivariate Analysis ; Non-alcoholic Fatty Liver Disease/*microbiology/physiopathology ; Obesity/*microbiology/physiopathology ; Pediatrics ; Proteogenomics/methods ; Reference Values ; Sensitivity and Specificity ; }, abstract = {UNLABELLED: There is evidence that nonalcoholic fatty liver disease (NAFLD) is affected by gut microbiota. Therefore, we investigated its modifications in pediatric NAFLD patients using targeted metagenomics and metabolomics. Stools were collected from 61 consecutive patients diagnosed with nonalcoholic fatty liver (NAFL), nonalcoholic steatohepatitis (NASH), or obesity and 54 healthy controls (CTRLs), matched in a case-control fashion. Operational taxonomic units were pyrosequenced targeting 16S ribosomal RNA and volatile organic compounds determined by solid-phase microextraction gas chromatography-mass spectrometry. The α-diversity was highest in CTRLs, followed by obese, NASH, and NAFL patients; and β-diversity distinguished between patients and CTRLs but not NAFL and NASH. Compared to CTRLs, in NAFLD patients Actinobacteria were significantly increased and Bacteroidetes reduced. There were no significant differences among the NAFL, NASH, and obese groups. Overall NAFLD patients had increased levels of Bradyrhizobium, Anaerococcus, Peptoniphilus, Propionibacterium acnes, Dorea, and Ruminococcus and reduced proportions of Oscillospira and Rikenellaceae compared to CTRLs. After reducing metagenomics and metabolomics data dimensionality, multivariate analyses indicated a decrease of Oscillospira in NAFL and NASH groups and increases of Ruminococcus, Blautia, and Dorea in NASH patients compared to CTRLs. Of the 292 volatile organic compounds, 26 were up-regulated and 2 down-regulated in NAFLD patients. Multivariate analyses found that combination of Oscillospira, Rickenellaceae, Parabacteroides, Bacteroides fragilis, Sutterella, Lachnospiraceae, 4-methyl-2-pentanone, 1-butanol, and 2-butanone could discriminate NAFLD patients from CTRLs. Univariate analyses found significantly lower levels of Oscillospira and higher levels of 1-pentanol and 2-butanone in NAFL patients compared to CTRLs. In NASH, lower levels of Oscillospira were associated with higher abundance of Dorea and Ruminococcus and higher levels of 2-butanone and 4-methyl-2-pentanone compared to CTRLs.<br><br>CONCLUSION: An Oscillospira decrease coupled to a 2-butanone up-regulation and increases in Ruminococcus and Dorea were identified as gut microbiota signatures of NAFL onset and NAFL-NASH progression, respectively. (Hepatology 2017;65:451-464).}, }
@article {pmid27025836, year = {2016}, author = {Millan, B and Park, H and Hotte, N and Mathieu, O and Burguiere, P and Tompkins, TA and Kao, D and Madsen, KL}, title = {Fecal Microbial Transplants Reduce Antibiotic-resistant Genes in Patients With Recurrent Clostridium difficile Infection.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {62}, number = {12}, pages = {1479-1486}, pmid = {27025836}, issn = {1537-6591}, support = {93675//CIHR/Canada ; }, mesh = {Adult ; Aged ; Aged, 80 and over ; Anti-Bacterial Agents/pharmacology ; Clostridioides difficile/*drug effects/genetics ; Drug Resistance, Bacterial/*genetics ; Enterocolitis, Pseudomembranous/microbiology/*therapy ; *Fecal Microbiota Transplantation ; Feces/microbiology ; Female ; Gastrointestinal Microbiome/*genetics ; Humans ; Male ; Middle Aged ; }, abstract = {BACKGROUND: Recurrent Clostridium difficile infection (RCDI) is associated with repeated antibiotic treatment and the enhanced growth of antibiotic-resistant microbes. This study tested the hypothesis that patients with RCDI would harbor large numbers of antibiotic-resistant microbes and that fecal microbiota transplantation (FMT) would reduce the number of antibiotic-resistant genes.<br><br>METHODS: In a single center study, patients with RCDI (n = 20) received FMT from universal donors via colonoscopy. Stool samples were collected from donors (n = 3) and patients prior to and following FMT. DNA was extracted and shotgun metagenomics performed. Results as well as assembled libraries from a healthy cohort (n = 87) obtained from the Human Microbiome Project were aligned against the NCBI bacterial taxonomy database and the Comprehensive Antibiotic Resistance Database. Results were corroborated through a DNA microarray containing 354 antibiotic resistance (ABR) genes.<br><br>RESULTS: RCDI patients had a greater number and diversity of ABR genes compared with donors and healthy controls. Beta-lactam, multidrug efflux pumps, fluoroquinolone, and antibiotic inactivation ABR genes were increased in RCDI patients, although donors primarily had tetracycline resistance. RCDI patients were dominated by Proteobacteria with Escherichia coli and Klebsiella most prevalent. FMT resulted in a resolution of symptoms that correlated directly with a decreased number and diversity of ABR genes and increased Bacteroidetes and Firmicutes with reduced Proteobacteria. ABR gene profiles were maintained in recipients for up to a year following FMT.<br><br>CONCLUSIONS: RCDI patients have increased numbers of antibiotic-resistant organisms. FMT is effective in the eradication of pathogenic antibiotic-resistant organisms and elimination of ABR genes.}, }
@article {pmid27017007, year = {2016}, author = {Woloszynek, S and Pastor, S and Mell, JC and Nandi, N and Sokhansanj, B and Rosen, GL}, title = {Engineering Human Microbiota: Influencing Cellular and Community Dynamics for Therapeutic Applications.}, journal = {International review of cell and molecular biology}, volume = {324}, number = {}, pages = {67-124}, doi = {10.1016/bs.ircmb.2016.01.003}, pmid = {27017007}, issn = {1937-6448}, mesh = {Animals ; Bioethics ; *Genetic Engineering ; Humans ; *Microbiota ; Models, Biological ; Social Control, Formal ; }, abstract = {The complex relationship between microbiota, human physiology, and environmental perturbations has become a major research focus, particularly with the arrival of culture-free and high-throughput approaches for studying the microbiome. Early enthusiasm has come from results that are largely correlative, but the correlative phase of microbiome research has assisted in defining the key questions of how these microbiota interact with their host. An emerging repertoire for engineering the microbiome places current research on a more experimentally grounded footing. We present a detailed look at the interplay between microbiota and host and how these interactions can be exploited. A particular emphasis is placed on unstable microbial communities, or dysbiosis, and strategies to reestablish stability in these microbial ecosystems. These include manipulation of intermicrobial communication, development of designer probiotics, fecal microbiota transplantation, and synthetic biology.}, }
@article {pmid27002979, year = {2016}, author = {Wu, P and Feldman, AS and Rosas-Salazar, C and James, K and Escobar, G and Gebretsadik, T and Li, SX and Carroll, KN and Walsh, E and Mitchel, E and Das, S and Kumar, R and Yu, C and Dupont, WD and Hartert, TV}, title = {Relative Importance and Additive Effects of Maternal and Infant Risk Factors on Childhood Asthma.}, journal = {PloS one}, volume = {11}, number = {3}, pages = {e0151705}, pmid = {27002979}, issn = {1932-6203}, support = {K24 AI077930/AI/NIAID NIH HHS/United States ; R01 HS018454/HS/AHRQ HHS/United States ; U19 AI110819/AI/NIAID NIH HHS/United States ; K24 AI 077930/AI/NIAID NIH HHS/United States ; }, mesh = {Anti-Bacterial Agents/*adverse effects ; Asthma/*epidemiology ; Cesarean Section/adverse effects ; Delivery, Obstetric/adverse effects ; Dose-Response Relationship, Drug ; Female ; Humans ; Maternal Exposure/*adverse effects ; Microbiota/physiology ; Pregnancy ; *Prenatal Exposure Delayed Effects ; Risk Factors ; Siblings ; Urinary Tract Infections/complications ; }, abstract = {BACKGROUND: Environmental exposures that occur in utero and during early life may contribute to the development of childhood asthma through alteration of the human microbiome. The objectives of this study were to estimate the cumulative effect and relative importance of environmental exposures on the risk of childhood asthma.<br><br>METHODS: We conducted a population-based birth cohort study of mother-child dyads who were born between 1995 and 2003 and were continuously enrolled in the PRIMA (Prevention of RSV: Impact on Morbidity and Asthma) cohort. The individual and cumulative impact of maternal urinary tract infections (UTI) during pregnancy, maternal colonization with group B streptococcus (GBS), mode of delivery, infant antibiotic use, and older siblings at home, on the risk of childhood asthma were estimated using logistic regression. Dose-response effect on childhood asthma risk was assessed for continuous risk factors: number of maternal UTIs during pregnancy, courses of infant antibiotics, and number of older siblings at home. We further assessed and compared the relative importance of these exposures on the asthma risk. In a subgroup of children for whom maternal antibiotic use during pregnancy information was available, the effect of maternal antibiotic use on the risk of childhood asthma was estimated.<br><br>RESULTS: Among 136,098 singleton birth infants, 13.29% developed asthma. In both univariate and adjusted analyses, maternal UTI during pregnancy (odds ratio [OR] 1.2, 95% confidence interval [CI] 1.18, 1.25; adjusted OR [AOR] 1.04, 95%CI 1.02, 1.07 for every additional UTI) and infant antibiotic use (OR 1.21, 95%CI 1.20, 1.22; AOR 1.16, 95%CI 1.15, 1.17 for every additional course) were associated with an increased risk of childhood asthma, while having older siblings at home (OR 0.92, 95%CI 0.91, 0.93; AOR 0.85, 95%CI 0.84, 0.87 for each additional sibling) was associated with a decreased risk of childhood asthma, in a dose-dependent manner. Compared with vaginal delivery, C-section delivery increased odds of childhood asthma by 34% (OR 1.34, 95%CI 1.29, 1.39) in the univariate analysis and 11% after adjusting for other environmental exposures and covariates (AOR 1.11, 95%CI 1.06, 1.15). Maternal GBS was associated with a significant increased risk of childhood asthma in the univariate analysis (OR 1.27, 95%CI 1.19, 1.35), but not in the adjusted analysis (AOR 1.03, 95%CI 0.96, 1.10). In the subgroup analysis of children whose maternal antibiotic use information was available, maternal antibiotic use was associated with an increased risk of childhood asthma in a similar dose-dependent manner in the univariate and adjusted analyses (OR 1.13, 95%CI 1.12, 1.15; AOR 1.06, 95%CI 1.05, 1.08 for every additional course). Compared with infants with the lowest number of exposures (no UTI during pregnancy, vaginal delivery, at least five older siblings at home, no antibiotics during infancy), infants with the highest number of exposures (at least three UTIs during pregnancy, C-section delivery, no older siblings, eight or more courses of antibiotics during infancy) had a 7.77 fold increased odds of developing asthma (AOR: 7.77, 95%CI: 6.25, 9.65). Lastly, infant antibiotic use had the greatest impact on asthma risk compared with maternal UTI during pregnancy, mode of delivery and having older siblings at home.<br><br>CONCLUSION: Early-life exposures, maternal UTI during pregnancy (maternal antibiotic use), mode of delivery, infant antibiotic use, and having older siblings at home, are associated with an increased risk of childhood asthma in a cumulative manner, and for those continuous variables, a dose-dependent relationship. Compared with in utero exposures, exposures occurring during infancy have a greater impact on the risk of developing childhood asthma.}, }
@article {pmid26996766, year = {2016}, author = {Konikoff, T and Gophna, U}, title = {Oscillospira: a Central, Enigmatic Component of the Human Gut Microbiota.}, journal = {Trends in microbiology}, volume = {24}, number = {7}, pages = {523-524}, doi = {10.1016/j.tim.2016.02.015}, pmid = {26996766}, issn = {1878-4380}, mesh = {Adult ; *Body Mass Index ; Butyrates/metabolism ; Clostridiales/genetics/*growth &amp; development ; DNA, Bacterial/genetics ; Diet, Vegetarian ; *Gastrointestinal Microbiome ; Humans ; RNA, Ribosomal, 16S/genetics ; Thinness/*microbiology ; Young Adult ; }, abstract = {Oscillospira is an enigmatic bacterial genus that has never been cultured, but is constantly detected by 16S rRNA gene surveys of the human microbiome. Here we summarize recent evidence that Oscillospira is positively associated with leanness and health, speculate about its physiology, and argue its potential importance for human health.}, }
@article {pmid26992958, year = {2016}, author = {Daly, K and Darby, AC and Shirazi-Beechey, SP}, title = {Low calorie sweeteners and gut microbiota.}, journal = {Physiology &amp; behavior}, volume = {164}, number = {Pt B}, pages = {494-500}, doi = {10.1016/j.physbeh.2016.03.014}, pmid = {26992958}, issn = {1873-507X}, mesh = {Animals ; Feces/microbiology ; Gastrointestinal Microbiome/*physiology ; Humans ; Intestines/microbiology ; Lactobacillus/metabolism ; Non-Nutritive Sweeteners/*administration &amp; dosage/chemistry ; Sus scrofa ; }, abstract = {Studies dating back to 1980s, using bacterial cultures, have reported associations between low calorie sweeteners (LCS) and alterations in bacterial composition, raising the potential that LCS might exert effects on the host via interactions with gut microbiota. However, the results of a few recent studies carried out in this area have produced controversies. There is evidence that human fecal samples, used in most human microbiome studies, may provide a poor representation of microbial contents of the proximal intestine. Furthermore, fecal short chain fatty acid levels do not exemplify the amount of short chain fatty acids produced in the intestine. Short chain fatty acids are largely absorbed in the intestine by a tightly regulated mechanism. Here we present an exemplar study showing that the determination of the molecular mechanism(s) underlying the precise mode of action of a LCS on gut microbiota allows for rational and scientifically-based recommendations.}, }
@article {pmid26973621, year = {2016}, author = {Patrignani, F and Chinnici, F and Serrazanetti, DI and Vernocchi, P and Ndagijimana, M and Riponi, C and Lanciotti, R}, title = {Production of Volatile and Sulfur Compounds by 10 Saccharomyces cerevisiae Strains Inoculated in Trebbiano Must.}, journal = {Frontiers in microbiology}, volume = {7}, number = {}, pages = {243}, pmid = {26973621}, issn = {1664-302X}, abstract = {In wines, the presence of sulfur compounds is the resulting of several contributions among which yeast metabolism. The characterization of the starter Saccharomyces cerevisiae needs to be performed also taking into account this ability even if evaluated together with the overall metabolic profile. In this perspective, principal aim of this experimental research was the evaluation of the volatile profiles, throughout GC/MS technique coupled with solid phase micro extraction, of wines obtained throughout the fermentation of 10 strains of S. cerevisiae. In addition, the production of sulfur compounds was further evaluated by using a gas-chromatograph coupled with a Flame Photometric Detector. Specifically, the 10 strains were inoculated in Trebbiano musts and the fermentations were monitored for 19 days. In the produced wines, volatile and sulfur compounds as well as amino acid concentrations were investigated. Also the physico-chemical characteristics of the wines and their electronic nose profiles were evaluated.}, }
@article {pmid26965030, year = {2016}, author = {Armstrong, D and Ashworth, M and Dregan, A and White, P}, title = {The relationship between prior antimicrobial prescription and meningitis: a case-control study.}, journal = {The British journal of general practice : the journal of the Royal College of General Practitioners}, volume = {66}, number = {645}, pages = {e228-33}, pmid = {26965030}, issn = {1478-5242}, mesh = {Anti-Infective Agents/*administration &amp; dosage ; Case-Control Studies ; Humans ; Logistic Models ; Meningitis, Bacterial/epidemiology/*immunology ; Meningitis, Viral/epidemiology/*immunology ; Nasopharynx/*immunology/microbiology/virology ; Practice Patterns, Physicians'/*statistics &amp; numerical data ; Risk Factors ; United Kingdom/epidemiology ; }, abstract = {BACKGROUND: Recent research into the role of the human microbiome in maintaining health has identified the potentially harmful impact of antimicrobials.<br><br>AIM: The association with bacterial and viral meningitis following antimicrobial prescription during the previous year was investigated to determine whether antimicrobials have a deleterious effect on the nasopharyngeal microbiome.<br><br>DESIGN AND SETTING: A case-control study (1:4 cases to controls) was conducted examining the rate of previous antimicrobial exposure in cases of meningitis and in a matched control group. Data from a UK primary care clinical database were analysed using conditional logistic regression.<br><br>RESULTS: A total of 7346 cases of meningitis were identified, 3307 (45%) viral, 1812 (25%) bacterial, and 2227 (30%) unspecified. The risks of viral (adjusted odds ratio [AOR] 2.45; 95% confidence interval [CI] = 2.24 to 2.68) or bacterial (AOR 1.98; 95% CI = 1.71 to 2.30) meningitis were both increased following antimicrobial prescription in the preceding year. Patients who received &#x2265;4 antimicrobial prescriptions in the preceding year were at significantly increased risk of all types of meningitis (AOR 2.85; 95% CI = 2.44 to 3.34), bacterial meningitis (AOR 3.06; 95% CI = 2.26 to 4.15) and viral meningitis (AOR 3.23; 95% CI = 2.55 to 4.08) compared to their matched controls.<br><br>CONCLUSION: There was an increased risk of meningitis following antimicrobial prescription in the previous year. It is possible that this increase was due to an effect of antimicrobials on the microbiome or reflected an increased general susceptibility to infections in these patients.}, }
@article {pmid26962018, year = {2016}, author = {Ferrer, MD and Mira, A}, title = {Oral Biofilm Architecture at the Microbial Scale.}, journal = {Trends in microbiology}, volume = {24}, number = {4}, pages = {246-248}, doi = {10.1016/j.tim.2016.02.013}, pmid = {26962018}, issn = {1878-4380}, mesh = {Bacteria/*classification ; Humans ; *Microbiota ; Mouth/*microbiology ; *Phylogeography ; }, abstract = {The application of Spectral Imaging FISH to oral biofilm samples has permitted the direct, simultaneous observation of up to nine different bacterial taxa. This has revealed a complex yet organized microbial architecture, identifying the key microorganisms in the community and detecting the existing interspecies physical interactions at the micron scale.}, }
@article {pmid26954507, year = {2016}, author = {Oh, J and Choi, CH and Park, MK and Kim, BK and Hwang, K and Lee, SH and Hong, SG and Nasir, A and Cho, WS and Kim, KM}, title = {CLUSTOM-CLOUD: In-Memory Data Grid-Based Software for Clustering 16S rRNA Sequence Data in the Cloud Environment.}, journal = {PloS one}, volume = {11}, number = {3}, pages = {e0151064}, pmid = {26954507}, issn = {1932-6203}, mesh = {*Cluster Analysis ; Computational Biology/methods ; *Environmental Microbiology ; Humans ; RNA, Ribosomal, 16S/*genetics ; Reproducibility of Results ; *Software ; Workflow ; }, abstract = {High-throughput sequencing can produce hundreds of thousands of 16S rRNA sequence reads corresponding to different organisms present in the environmental samples. Typically, analysis of microbial diversity in bioinformatics starts from pre-processing followed by clustering 16S rRNA reads into relatively fewer operational taxonomic units (OTUs). The OTUs are reliable indicators of microbial diversity and greatly accelerate the downstream analysis time. However, existing hierarchical clustering algorithms that are generally more accurate than greedy heuristic algorithms struggle with large sequence datasets. To keep pace with the rapid rise in sequencing data, we present CLUSTOM-CLOUD, which is the first distributed sequence clustering program based on In-Memory Data Grid (IMDG) technology-a distributed data structure to store all data in the main memory of multiple computing nodes. The IMDG technology helps CLUSTOM-CLOUD to enhance both its capability of handling larger datasets and its computational scalability better than its ancestor, CLUSTOM, while maintaining high accuracy. Clustering speed of CLUSTOM-CLOUD was evaluated on published 16S rRNA human microbiome sequence datasets using the small laboratory cluster (10 nodes) and under the Amazon EC2 cloud-computing environments. Under the laboratory environment, it required only ~3 hours to process dataset of size 200 K reads regardless of the complexity of the human microbiome data. In turn, one million reads were processed in approximately 20, 14, and 11 hours when utilizing 20, 30, and 40 nodes on the Amazon EC2 cloud-computing environment. The running time evaluation indicates that CLUSTOM-CLOUD can handle much larger sequence datasets than CLUSTOM and is also a scalable distributed processing system. The comparative accuracy test using 16S rRNA pyrosequences of a mock community shows that CLUSTOM-CLOUD achieves higher accuracy than DOTUR, mothur, ESPRIT-Tree, UCLUST and Swarm. CLUSTOM-CLOUD is written in JAVA and is freely available at http://clustomcloud.kopri.re.kr.}, }
@article {pmid26953630, year = {2016}, author = {van der Meulen, TA and Harmsen, H and Bootsma, H and Spijkervet, F and Kroese, F and Vissink, A}, title = {The microbiome-systemic diseases connection.}, journal = {Oral diseases}, volume = {22}, number = {8}, pages = {719-734}, doi = {10.1111/odi.12472}, pmid = {26953630}, issn = {1601-0825}, mesh = {Autoimmune Diseases/etiology/*microbiology ; Gastrointestinal Microbiome ; Humans ; Immunity/physiology ; *Microbiota ; Mouth/*microbiology ; Mouth Mucosa/immunology/microbiology ; }, abstract = {The human microbiome consists of all microorganisms occupying the skin, mucous membranes and intestinal tract of the human body. The contact of the mucosal immune system with the human microbiome is a balanced interplay between defence mechanisms of the immune system and symbiotic or pathogenic microbial factors, such as microbial antigens and metabolites. In systemic autoimmune diseases (SADs) such as rheumatoid arthritis, systemic lupus erythematosus and Sjögren's syndrome, the immune system is deranged to a chronic inflammatory state and autoantibodies are an important hallmark. Specific bacteria and/or a dysbiosis in the human microbiome can lead to local mucosal inflammation and increased intestinal permeability. Proinflammatory lymphocytes and cytokines can spread to the systemic circulation and increase the risk of inflammation at distant anatomical sites, such as the joints or salivary glands. Increased intestinal permeability increases antigen exposure and the risk of autoantibody production. If the human microbiome indeed plays such a critical role in SADs, this finding holds a great promise for new therapeutic strategies, such as diet interventions and probiotics and prebiotics. This review provides a background on the human microbiome and mucosal immunity in the gut and oral cavity and gives a summary of the current knowledge on the microbiome-SADs connection.}, }
@article {pmid26945815, year = {2016}, author = {Williams, B and Landay, A and Presti, RM}, title = {Microbiome alterations in HIV infection a review.}, journal = {Cellular microbiology}, volume = {18}, number = {5}, pages = {645-651}, doi = {10.1111/cmi.12588}, pmid = {26945815}, issn = {1462-5822}, mesh = {Bacterial Translocation/genetics ; HIV/genetics/pathogenicity ; HIV Infections/genetics/*microbiology/virology ; Host-Pathogen Interactions/genetics ; Humans ; Intestinal Mucosa/*microbiology/virology ; Intestines/*microbiology/virology ; Microbiota/*genetics ; Probiotics/therapeutic use ; Reproductive Tract Infections/microbiology/virology ; }, abstract = {Recent developments in molecular techniques have allowed researchers to identify previously uncultured organisms, which has propelled a vast expansion of our knowledge regarding our commensal microbiota. Interest in the microbiome specific to HIV grew from earlier findings suggesting that bacterial translocation from the intestines is the cause of persistent immune activation despite effective viral suppression with antiretroviral therapy (ART). Studies of SIV infected primates have demonstrated that Proteobacteria preferentially translocate and that mucosal immunity can be restored with probiotics. Pathogenic SIV infection results in a massive expansion of the virome, whereas non-pathogenic SIV infection does not. Human HIV infected cohorts have been shown to have microbiota distinctive from that of HIV negative controls and efforts to restore the intestinal microbiome via probiotics have often had positive results on host markers. The microbiota of the genital tract may play a significant role in acquisition and transmission of HIV. Modification of commensal microbial communities likely represents an important therapeutic adjunct to treatment of HIV. Here we review the literature regarding human microbiome in HIV infection.}, }
@article {pmid26943627, year = {2016}, author = {Almeida, M and Pop, M and Le Chatelier, E and Prifti, E and Pons, N and Ghozlane, A and Ehrlich, SD}, title = {Capturing the most wanted taxa through cross-sample correlations.}, journal = {The ISME journal}, volume = {10}, number = {10}, pages = {2459-2467}, pmid = {26943627}, issn = {1751-7370}, support = {R01 AI100947/AI/NIAID NIH HHS/United States ; }, mesh = {Bacteria/*classification/genetics/*isolation &amp; purification ; Humans ; Metagenomics ; *Microbiota ; Phylogeny ; RNA, Ribosomal, 16S/genetics ; }, abstract = {The Human Microbiome Project (HMP) identified the 16S rRNA gene sequences of 'most wanted' taxa-prevalent in the healthy human microbiota but distant from previously known sequences. Since 2012, few of the corresponding genomes have been isolated and sequenced, and only through advanced isolation techniques. We demonstrate that the genomes of the most wanted taxa can be identified computationally through their correlation in abundance across multiple public metagenomic data sets. We link over 200 most wanted sequences with nearly complete genome sequences, including half of the taxa identified as high-priority targets by the HMP. The genomes we identify have strong similarity to genomes reconstructed through expensive isolation techniques, and provide a more complete functional characterization of these organisms than can be extrapolated from their 16S rRNA gene. We also provide insights into the function of organisms for which 16S rRNA gene signatures were recently reported to be associated with health and host genetic factors.}, }
@article {pmid26941736, year = {2016}, author = {Javan, GT and Finley, SJ and Abidin, Z and Mulle, JG}, title = {The Thanatomicrobiome: A Missing Piece of the Microbial Puzzle of Death.}, journal = {Frontiers in microbiology}, volume = {7}, number = {}, pages = {225}, pmid = {26941736}, issn = {1664-302X}, abstract = {Death is a universal phenomenon; however, is there "life after death?" This topic has been investigated for centuries but still there are gray areas that have yet to be elucidated. Forensic microbiologists are developing new applications to investigate the dynamic and coordinated changes in microbial activity that occur when a human host dies. There is currently a paucity of explorations of the thanatomicrobiome (thanatos-, Greek for death) and epinecrotic communities (microbial communities residing in and/or moving on the surface of decomposing remains). Ongoing studies can help clarify the structure and function of these postmortem microbiomes. Human microbiome studies have revealed that 75-90% of cells in the body prior to death are microbial. Upon death, putrefaction occurs and is a complicated process encompassing chemical degradation and autolysis of cells. Decomposition also involves the release of contents of the intestines due to enzymes under the effects of abiotic and biotic factors. These factors likely have predictable effects on postmortem microbial communities and can be leveraged for forensic studies. This mini review provides a critical examination of emerging research relating to thanatomicrobiome and epinecrotic communities, how each is studied, and possible strategies of stochastic processes.}, }
@article {pmid26939849, year = {2016}, author = {Ridlon, JM and Harris, SC and Bhowmik, S and Kang, DJ and Hylemon, PB}, title = {Consequences of bile salt biotransformations by intestinal bacteria.}, journal = {Gut microbes}, volume = {7}, number = {1}, pages = {22-39}, pmid = {26939849}, issn = {1949-0984}, support = {I01 BX001328/BX/BLRD VA/United States ; }, mesh = {Amino Acids/metabolism ; Bacteria/*metabolism ; Bile Acids and Salts/*metabolism ; Diet ; *Energy Metabolism ; Gastrointestinal Microbiome/*physiology ; Humans ; Receptors, Cytoplasmic and Nuclear/*metabolism ; Receptors, G-Protein-Coupled/*metabolism ; }, abstract = {Emerging evidence strongly suggest that the human "microbiome" plays an important role in both health and disease. Bile acids function both as detergents molecules promoting nutrient absorption in the intestines and as hormones regulating nutrient metabolism. Bile acids regulate metabolism via activation of specific nuclear receptors (NR) and G-protein coupled receptors (GPCRs). The circulating bile acid pool composition consists of primary bile acids produced from cholesterol in the liver, and secondary bile acids formed by specific gut bacteria. The various biotransformation of bile acids carried out by gut bacteria appear to regulate the structure of the gut microbiome and host physiology. Increased levels of secondary bile acids are associated with specific diseases of the GI system. Elucidating methods to control the gut microbiome and bile acid pool composition in humans may lead to a reduction in some of the major diseases of the liver, gall bladder and colon.}, }
@article {pmid26936188, year = {2016}, author = {Vinturache, AE and Gyamfi-Bannerman, C and Hwang, J and Mysorekar, IU and Jacobsson, B and , }, title = {Maternal microbiome - A pathway to preterm birth.}, journal = {Seminars in fetal &amp; neonatal medicine}, volume = {21}, number = {2}, pages = {94-99}, doi = {10.1016/j.siny.2016.02.004}, pmid = {26936188}, issn = {1878-0946}, mesh = {Cervix Uteri/microbiology ; Dysbiosis/microbiology/*physiopathology ; Female ; Humans ; Intestinal Mucosa/microbiology ; *Microbiota ; Mouth Mucosa/microbiology ; Placenta/microbiology ; Pregnancy ; Premature Birth/*etiology/microbiology ; Vagina/microbiology ; }, abstract = {Despite great medical advances in preventing maternal and infant mortality in the past century, one issue remains unresolved: why do so many women give birth prematurely? A major new field of human microbiome studies has begun to shed light on the impact of microbes (of both the commensal and pathogen varieties) on pregnancy outcomes. Recent advances in next-generation sequencing and metagenomic analysis have revealed that maternal microbiomes at a variety of niches including the oral, vaginal, gut, cervical, and even the placenta itself govern pregnancy outcomes. In this review, we describe how alterations in the microbial biomasses impact preterm birth and we discuss the major research questions concerning the cause and/or interdependent relationships between microbiome, infection, and preterm delivery.}, }
@article {pmid26933683, year = {2016}, author = {Ruiz-Calderon, JF and Cavallin, H and Song, SJ and Novoselac, A and Pericchi, LR and Hernandez, JN and Rios, R and Branch, OH and Pereira, H and Paulino, LC and Blaser, MJ and Knight, R and Dominguez-Bello, MG}, title = {Walls talk: Microbial biogeography of homes spanning urbanization.}, journal = {Science advances}, volume = {2}, number = {2}, pages = {e1501061}, pmid = {26933683}, issn = {2375-2548}, support = {P20 GM103475/GM/NIGMS NIH HHS/United States ; R25 GM061151/GM/NIGMS NIH HHS/United States ; }, mesh = {Bacteria/classification/genetics/isolation &amp; purification ; *Environmental Microbiology ; Housing ; Humans ; *Microbiota ; Phylogeography ; South America ; *Urbanization ; }, abstract = {Westernization has propelled changes in urbanization and architecture, altering our exposure to the outdoor environment from that experienced during most of human evolution. These changes might affect the developmental exposure of infants to bacteria, immune development, and human microbiome diversity. Contemporary urban humans spend most of their time indoors, and little is known about the microbes associated with different designs of the built environment and their interaction with the human immune system. This study addresses the associations between architectural design and the microbial biogeography of households across a gradient of urbanization in South America. Urbanization was associated with households' increased isolation from outdoor environments, with additional indoor space isolation by walls. Microbes from house walls and floors segregate by location, and urban indoor walls contain human bacterial markers of space use. Urbanized spaces uniquely increase the content of human-associated microbes-which could increase transmission of potential pathogens-and decrease exposure to the environmental microbes with which humans have coevolved.}, }
@article {pmid26932765, year = {2016}, author = {Rampelli, S and Soverini, M and Turroni, S and Quercia, S and Biagi, E and Brigidi, P and Candela, M}, title = {ViromeScan: a new tool for metagenomic viral community profiling.}, journal = {BMC genomics}, volume = {17}, number = {}, pages = {165}, pmid = {26932765}, issn = {1471-2164}, mesh = {Computational Biology ; DNA, Viral ; *Genome, Viral ; High-Throughput Nucleotide Sequencing ; Humans ; Metagenomics/*methods ; *Microbiota ; RNA, Viral/isolation &amp; purification ; Sequence Analysis, DNA ; *Software ; Viruses/*classification/isolation &amp; purification ; }, abstract = {BACKGROUND: Bioinformatics tools available for metagenomic sequencing analysis are principally devoted to the identification of microorganisms populating an ecological niche, but they usually do not consider viruses. Only some software have been designed to profile the viral sequences, however they are not efficient in the characterization of viruses in the context of complex communities, like the intestinal microbiota, containing bacteria, archeabacteria, eukaryotic microorganisms and viruses. In any case, a comprehensive description of the host-microbiota interactions can not ignore the profile of eukaryotic viruses within the virome, as viruses are definitely critical for the regulation of the host immunophenotype.<br><br>RESULTS: ViromeScan is an innovative metagenomic analysis tool that characterizes the taxonomy of the virome directly from raw data of next-generation sequencing. The tool uses hierarchical databases for eukaryotic viruses to unambiguously assign reads to viral species more accurately and >1000 fold faster than other existing approaches. We validated ViromeScan on synthetic microbial communities and applied it on metagenomic samples of the Human Microbiome Project, providing a sensitive eukaryotic virome profiling of different human body sites.<br><br>CONCLUSIONS: ViromeScan allows the user to explore and taxonomically characterize the virome from metagenomic reads, efficiently denoising samples from reads of other microorganisms. This implies that users can fully characterize the microbiome, including bacteria and viruses, by shotgun metagenomic sequencing followed by different bioinformatic pipelines.}, }
@article {pmid26884067, year = {2016}, author = {Yassour, M and Lim, MY and Yun, HS and Tickle, TL and Sung, J and Song, YM and Lee, K and Franzosa, EA and Morgan, XC and Gevers, D and Lander, ES and Xavier, RJ and Birren, BW and Ko, G and Huttenhower, C}, title = {Sub-clinical detection of gut microbial biomarkers of obesity and type 2 diabetes.}, journal = {Genome medicine}, volume = {8}, number = {1}, pages = {17}, pmid = {26884067}, issn = {1756-994X}, support = {P30 DK043351/DK/NIDDK NIH HHS/United States ; R01 HG005969/HG/NHGRI NIH HHS/United States ; }, mesh = {Adult ; Diabetes Mellitus, Type 2/*microbiology ; Dysbiosis/*microbiology ; Feces/microbiology ; Female ; *Gastrointestinal Microbiome ; Healthy Volunteers ; Humans ; Male ; Middle Aged ; Obesity/*microbiology ; Phylogeny ; Risk Factors ; Twins, Monozygotic ; Verrucomicrobia/*classification/genetics/*isolation &amp; purification ; }, abstract = {BACKGROUND: Obesity and type 2 diabetes (T2D) are linked both with host genetics and with environmental factors, including dysbioses of the gut microbiota. However, it is unclear whether these microbial changes precede disease onset. Twin cohorts present a unique genetically-controlled opportunity to study the relationships between lifestyle factors and the microbiome. In particular, we hypothesized that family-independent changes in microbial composition and metabolic function during the sub-clinical state of T2D could be either causal or early biomarkers of progression.<br><br>METHODS: We collected fecal samples and clinical metadata from 20 monozygotic Korean twins at up to two time points, resulting in 36 stool shotgun metagenomes. While the participants were neither obese nor diabetic, they spanned the entire range of healthy to near-clinical values and thus enabled the study of microbial associations during sub-clinical disease while accounting for genetic background.<br><br>RESULTS: We found changes both in composition and in function of the sub-clinical gut microbiome, including a decrease in Akkermansia muciniphila suggesting a role prior to the onset of disease, and functional changes reflecting a response to oxidative stress comparable to that previously observed in chronic T2D and inflammatory bowel diseases. Finally, our unique study design allowed us to examine the strain similarity between twins, and we found that twins demonstrate strain-level differences in composition despite species-level similarities.<br><br>CONCLUSIONS: These changes in the microbiome might be used for the early diagnosis of an inflamed gut and T2D prior to clinical onset of the disease and will help to advance toward microbial interventions.}, }
@article {pmid26877759, year = {2016}, author = {Kvist, LJ}, title = {Diagnostic methods for mastitis in cows are not appropriate for use in humans: commentary.}, journal = {International breastfeeding journal}, volume = {11}, number = {}, pages = {2}, pmid = {26877759}, issn = {1746-4358}, abstract = {Healthcare workers are now being targeted for marketing of diagnostic tools for mastitis that were developed for the dairy industry and which aim to provide information regarding choice of antibiotic treatment. Meanwhile, scientists are striving to understand how the human microbiome affects health and wellbeing and the importance of maintenance of bacterial balance in the human body. Breast milk supplies a multitude of bacteria to populate the baby's intestinal tract and kick-start the immune system. Researchers propose a paradigm shift in the understanding of bacterial content in breast milk and an alternative paradigm for the understanding of lactational mastitis: there is the beginning of evidence that many cases of lactational mastitis will resolve spontaneously. An international group of researchers is attempting to answer how dietary habits, birth mode, genetics and environmental factors may impact the bacterial content of breast milk. Until we have more comprehensive knowledge about the human milk microbiome, diagnostic aids for identification of women in need of antibiotic therapy for mastitis remain unreliable. Diagnostic aids could lead to the injudicious use of antibiotic therapy, which in turn may rob the infant of bacteria valuable for development of its immune system. The marketing of diagnostic aids for use in human medicine, that were originally developed for use in cows, is neither evidence-based nor good ethical practice.}, }
@article {pmid26870828, year = {2016}, author = {Hua, X and Goedert, JJ and Pu, A and Yu, G and Shi, J}, title = {Allergy associations with the adult fecal microbiota: Analysis of the American Gut Project.}, journal = {EBioMedicine}, volume = {3}, number = {}, pages = {172-179}, pmid = {26870828}, issn = {2352-3964}, support = {ZIA CP010214//Intramural NIH HHS/United States ; ZIA-CP-010214/CP/NCI NIH HHS/United States ; }, mesh = {Adult ; Aged ; Biodiversity ; Databases, Nucleic Acid ; Feces/*microbiology ; Female ; *Gastrointestinal Microbiome ; Humans ; Hypersensitivity/*epidemiology/*etiology ; Male ; Metagenome ; Metagenomics/methods ; Middle Aged ; Odds Ratio ; RNA, Ribosomal, 16S/genetics ; Risk ; Surveys and Questionnaires ; }, abstract = {BACKGROUND: Alteration of the gut microbial population (dysbiosis) may increase the risk for allergies and other conditions. This study sought to clarify the relationship of dysbiosis with allergies in adults.<br><br>METHODS: Publicly available American Gut Project questionnaire and fecal 16S rRNA sequence data were analyzed. Fecal microbiota richness (number of observed species) and composition (UniFrac) were used to compare adults with versus without allergy to foods (peanuts, tree nuts, shellfish, other) and non-foods (drug, bee sting, dander, asthma, seasonal, eczema). Logistic and Poisson regression models adjusted for potential confounders. Odds ratios and 95% confidence intervals (CI) were calculated for lowest vs highest richness tertile. Taxonomy associations considered 122 non-redundant taxa (of 2379 total taxa) with &#x2265; 0.1% mean abundance.<br><br>RESULTS: Self-reported allergy prevalence among the 1879 participants (mean age, 45.5 years; 46.9% male) was 81.5%, ranging from 2.5% for peanuts to 40.5% for seasonal. Fecal microbiota richness was markedly lower with total allergies (P = 10(-9)) and five particular allergies (P &#x2264; 10(-4)). Richness odds ratios were 1.7 (CI 1.3-2.2) with seasonal, 1.8 (CI 1.3-2.5) with drug, and 7.8 (CI 2.3-26.5) with peanut allergy. These allergic participants also had markedly altered microbial community composition (unweighted UniFrac, P = 10(-4) to 10(-7)). Total food and non-food allergies were significantly associated with 7 and 9 altered taxa, respectively. The dysbiosis was most marked with nut and seasonal allergies, driven by higher Bacteroidales and reduced Clostridiales taxa.<br><br>INTERPRETATION: American adults with allergies, especially to nuts and seasonal pollen, have low diversity, reduced Clostridiales, and increased Bacteroidales in their gut microbiota. This dysbiosis might be targeted to improve treatment or prevention of allergy.}, }
@article {pmid26870014, year = {2016}, author = {Carbonetto, B and Fabbro, MC and Sciara, M and Seravalle, A and Méjico, G and Revale, S and Romero, MS and Brun, B and Fay, M and Fay, F and Vazquez, MP}, title = {Human Microbiota of the Argentine Population- A Pilot Study.}, journal = {Frontiers in microbiology}, volume = {7}, number = {}, pages = {51}, pmid = {26870014}, issn = {1664-302X}, abstract = {The human microbiota is the collection of microorganisms living in or on the human body. An imbalance or dysbiosis in these microbial communities can be associated with a wide variety of human diseases (Petersen and Round, 2014; Pham and Lawley, 2014; Zaura et al., 2014). Moreover, when the microbiota of the same body sites is compared between different healthy individuals, specific microbial community features are apparent (Li et al., 2012; Yatsunenko et al., 2012; Oh et al., 2014; Relman, 2015). In addition, specific selective pressures are found at distinct body sites leading to different patterns in microbial community structure and composition (Costello et al., 2009; Consortium, 2012b; Zhou et al., 2013). Because of these natural variations, a comprehensive characterization of the healthy microbiota is critical for predicting alterations related to diseases. This characterization should be based on a broad healthy population over time, geography, and culture (Yatsunenko et al., 2012; Shetty et al., 2013; Leung et al., 2015; Ross et al., 2015). The study of healthy individuals representing different ages, cultural traditions, and ethnic origins will enable to understand how the associated microbiota varies between populations and respond to different lifestyles. It is important to address these natural variations in order to later detect variations related to disease.}, }
@article {pmid26866806, year = {2016}, author = {Gibson, TE and Bashan, A and Cao, HT and Weiss, ST and Liu, YY}, title = {On the Origins and Control of Community Types in the Human Microbiome.}, journal = {PLoS computational biology}, volume = {12}, number = {2}, pages = {e1004688}, pmid = {26866806}, issn = {1553-7358}, support = {R01 HL091528/HL/NHLBI NIH HHS/United States ; }, mesh = {Algorithms ; Cluster Analysis ; Computational Biology ; Humans ; *Microbiota ; *Models, Biological ; }, abstract = {Microbiome-based stratification of healthy individuals into compositional categories, referred to as "enterotypes" or "community types", holds promise for drastically improving personalized medicine. Despite this potential, the existence of community types and the degree of their distinctness have been highly debated. Here we adopted a dynamic systems approach and found that heterogeneity in the interspecific interactions or the presence of strongly interacting species is sufficient to explain community types, independent of the topology of the underlying ecological network. By controlling the presence or absence of these strongly interacting species we can steer the microbial ecosystem to any desired community type. This open-loop control strategy still holds even when the community types are not distinct but appear as dense regions within a continuous gradient. This finding can be used to develop viable therapeutic strategies for shifting the microbial composition to a healthy configuration.}, }
@article {pmid26864580, year = {2016}, author = {Onderdonk, AB and Delaney, ML and Fichorova, RN}, title = {The Human Microbiome during Bacterial Vaginosis.}, journal = {Clinical microbiology reviews}, volume = {29}, number = {2}, pages = {223-238}, pmid = {26864580}, issn = {1098-6618}, mesh = {Bacteria/*classification/isolation &amp; purification ; DNA, Bacterial/analysis ; Female ; Humans ; Microbiota ; Vaginosis, Bacterial/*epidemiology/immunology/*microbiology ; }, abstract = {Bacterial vaginosis (BV) is the most commonly reported microbiological syndrome among women of childbearing age. BV is characterized by a shift in the vaginal flora from the dominant Lactobacillus to a polymicrobial flora. BV has been associated with a wide array of health issues, including preterm births, pelvic inflammatory disease, increased susceptibility to HIV infection, and other chronic health problems. A number of potential microbial pathogens, singly and in combinations, have been implicated in the disease process. The list of possible agents continues to expand and includes members of a number of genera, including Gardnerella, Atopobium, Prevotella, Peptostreptococcus, Mobiluncus, Sneathia, Leptotrichia, Mycoplasma, and BV-associated bacterium 1 (BVAB1) to BVAB3. Efforts to characterize BV using epidemiological, microscopic, microbiological culture, and sequenced-based methods have all failed to reveal an etiology that can be consistently documented in all women with BV. A careful analysis of the available data suggests that what we term BV is, in fact, a set of common clinical signs and symptoms that can be provoked by a plethora of bacterial species with proinflammatory characteristics, coupled to an immune response driven by variability in host immune function.}, }
@article {pmid26862305, year = {2015}, author = {Strus, M and Okoń, K and Nowak, B and Pilarczyk-Zurek, M and Heczko, P and Gawda, A and Ciszek-Lenda, M and Skowron, B and Baranowska, A and Marcinkiewicz, J}, title = {Distinct effects of Lactobacillus plantarum KL30B and Escherichia coli 3A1 on the induction and development of acute and chronic inflammation.}, journal = {Central-European journal of immunology}, volume = {40}, number = {4}, pages = {420-430}, pmid = {26862305}, issn = {1426-3912}, abstract = {OBJECTIVE: Enteric bacteria are involved in the pathogenesis of ulcerative colitis. In experimental colitis, a breakdown of the intestinal epithelial barrier results in inflow of various gut bacteria, induction of acute inflammation and finally, progression to chronic colitis.<br><br>MATERIAL AND METHODS: In the present study we compared pro-inflammatory properties of two bacterial strains isolated from human microbiome, Escherichia coli 3A1 and Lactobacillus plantarum KL30B. The study was performed using two experimental models of acute inflammation: peritonitis in mice and trinitrobenzenesulfonic acid (TNBS)-induced colitis in rats.<br><br>RESULTS: Both bacterial strains induced massive neutrophil infiltration upon injection into sterile peritoneal cavity. However, peritoneal exudate cells stimulated in vitro with E. coli 3A1, produced far more nitric oxide, than those stimulated with L. plantarum KL30B. Interestingly, distinct effect on the development of TNBS-induced colitis was observed after oral administration of the tested bacteria. Lactobacillus plantarum KL30B evoked strong acute colitis. On the contrary, the administration of E. coli 3A1 resulted in a progression of colitis to chronicity.<br><br>CONCLUSIONS: Our results show that distinct effects of bacterial administration on the development of ongoing inflammation is strain specific and depends on the final effect of cross-talk between bacteria and cells of the innate immune system.}, }
@article {pmid26855863, year = {2016}, author = {Urban, J and Fergus, DJ and Savage, AM and Ehlers, M and Menninger, HL and Dunn, RR and Horvath, JE}, title = {The effect of habitual and experimental antiperspirant and deodorant product use on the armpit microbiome.}, journal = {PeerJ}, volume = {4}, number = {}, pages = {e1605}, pmid = {26855863}, issn = {2167-8359}, abstract = {An ever expanding body of research investigates the human microbiome in general and the skin microbiome in particular. Microbiomes vary greatly from individual to individual. Understanding the factors that account for this variation, however, has proven challenging, with many studies able to account statistically for just a small proportion of the inter-individual variation in the abundance, species richness or composition of bacteria. The human armpit has long been noted to host a high biomass bacterial community, and recent studies have highlighted substantial inter-individual variation in armpit bacteria, even relative to variation among individuals for other body habitats. One obvious potential explanation for this variation has to do with the use of personal hygiene products, particularly deodorants and antiperspirants. Here we experimentally manipulate product use to examine the abundance, species richness, and composition of bacterial communities that recolonize the armpits of people with different product use habits. In doing so, we find that when deodorant and antiperspirant use were stopped, culturable bacterial density increased and approached that found on individuals who regularly do not use any product. In addition, when antiperspirants were subsequently applied, bacterial density dramatically declined. These culture-based results are in line with sequence-based comparisons of the effects of long-term product use on bacterial species richness and composition. Sequence-based analyses suggested that individuals who habitually use antiperspirant tended to have a greater richness of bacterial OTUs in their armpits than those who use deodorant. In addition, individuals who used antiperspirants or deodorants long-term, but who stopped using product for two or more days as part of this study, had armpit communities dominated by Staphylococcaceae, whereas those of individuals in our study who habitually used no products were dominated by Corynebacterium. Collectively these results suggest a strong effect of product use on the bacterial composition of armpits. Although stopping the use of deodorant and antiperspirant similarly favors presence of Staphylococcaceae over Corynebacterium, their differential modes of action exert strikingly different effects on the richness of other bacteria living in armpit communities.}, }
@article {pmid26855081, year = {2016}, author = {Pirrone, M and Pinciroli, R and Berra, L}, title = {Microbiome, biofilms, and pneumonia in the ICU.}, journal = {Current opinion in infectious diseases}, volume = {29}, number = {2}, pages = {160-166}, doi = {10.1097/QCO.0000000000000255}, pmid = {26855081}, issn = {1473-6527}, mesh = {Biofilms/*growth &amp; development ; Cystic Fibrosis/complications ; Humans ; *Intensive Care Units ; *Microbiota ; Pneumonia/*epidemiology/*etiology ; Pulmonary Disease, Chronic Obstructive/complications ; Respiration, Artificial/adverse effects ; }, abstract = {PURPOSE OF REVIEW: Lower respiratory tract infections remain one of the leading causes of death in the world. Recently, the introduction of molecular methods based on DNA sequencing and microarrays for the identification of nonculturable microorganisms and subspecies variations has challenged the previous 'one bug - one disease' paradigm, providing us with a broader view on human microbial communities and their role in the development of infectious diseases. The purpose of this review is to describe recent understanding of the role of microbiome and bacterial biofilm in the development of lung infections, and, at the same time, to present new areas of research opportunities.<br><br>RECENT FINDINGS: The review describes recent literature in cystic fibrosis patients, chronic obstructive pulmonary disease patients, and literature in mechanically ventilated patients that helped to elucidate the role of microbiome and biofilm formation in the development of pneumonia.<br><br>SUMMARY: The characterization of the human microbiome and biofilms has changed our understanding of lower respiratory tract infections. More comprehensive, sensitive, and fast methods for bacterial, fungal, and viral detection are warranted to establish the colonization of the lower respiratory tract in healthy individuals and sick patients. Future research might explore the global bacterial, fungal, and viral pulmonary ecosystems and their interdependence to target novel preventive approaches and therapeutic strategies in chronic and acute lung infections.}, }
@article {pmid26852737, year = {2016}, author = {Mammen, MJ and Sethi, S}, title = {COPD and the microbiome.}, journal = {Respirology (Carlton, Vic.)}, volume = {21}, number = {4}, pages = {590-599}, doi = {10.1111/resp.12732}, pmid = {26852737}, issn = {1440-1843}, mesh = {Anti-Bacterial Agents/therapeutic use ; Bronchoalveolar Lavage Fluid ; Disease Progression ; Female ; Gastrointestinal Tract/immunology/*microbiology ; Humans ; Lung/*microbiology/physiopathology ; *Microbiota ; Pulmonary Disease, Chronic Obstructive/immunology/microbiology/*physiopathology/therapy ; RNA, Ribosomal, 16S/chemistry ; Risk Factors ; Severity of Illness Index ; Smoking ; United States ; }, abstract = {Traditional culture techniques confirm that bacteria have an important role in Chronic Obstructive Pulmonary Disease (COPD). In individuals with COPD, acquisition of novel bacterial strains is associated with onset of acute exacerbation of COPD, which leads to further lung dysfunction and enormous health-care costs. Recent study of the human microbiome, the total composite of the bacteria on the human body, posited the microbiome as the last human organ studied, as the microbiome performs a multitude of metabolic functions absent in the human genome. The largest project to study the human microbiome was the National Institutes of Health (NIH) human microbiome project (HMP) started in 2007 to understand the 'normal' microbiome. However due to the presumption that the healthy human lung was sterile, the respiratory tract was not included in that study. The advent of next-generation sequencing technologies has allowed the investigation of the human respiratory microbiome, which revealed that the healthy lung does have a robust microbiome. Subsequent studies in individuals with COPD revealed that the microbiome composition fluctuates with severity of COPD, composition of the individual aero-digestive tract microbiomes, age, during an acute exacerbation of COPD and with the use of steroids and/or antibiotics. Understanding the impact of the microbiome on COPD progression and risk of exacerbation will lead to directed therapies for prevention of COPD progression and exacerbation.}, }
@article {pmid26847045, year = {2016}, author = {James, KM and MacDonald, KW and Chanyi, RM and Cadieux, PA and Burton, JP}, title = {Inhibition of Candida albicans biofilm formation and modulation of gene expression by probiotic cells and supernatant.}, journal = {Journal of medical microbiology}, volume = {65}, number = {4}, pages = {328-336}, doi = {10.1099/jmm.0.000226}, pmid = {26847045}, issn = {1473-5644}, mesh = {*Biofilms ; Candida albicans/*genetics/*physiology ; Epithelial Cells ; Fungal Proteins/*genetics ; *Gene Expression Regulation, Fungal ; Humans ; Hyphae/genetics/growth &amp; development ; Lactobacillus helveticus ; Lactobacillus plantarum ; Probiotics/*pharmacology ; Real-Time Polymerase Chain Reaction ; Streptococcus salivarius ; Transcription Factors ; }, abstract = {Oral candidiasis is a disease caused by opportunistic species of Candida that normally reside on human mucosal surfaces. The transition of Candida from budding yeast to filamentous hyphae allows for covalent attachment to oral epithelial cells, followed by biofilm formation, invasion and tissue damage. In this study, combinations of Lactobacillus plantarum SD5870, Lactobacillus helveticus CBS N116411 and Streptococcus salivarius DSM 14685 were assessed for their ability to inhibit the formation of and disrupt Candida albicans biofilms. Co-incubation with probiotic supernatants under hyphae-inducing conditions reduced C. albicans biofilm formation by >75 % in all treatment groups. Likewise, combinations of live probiotics reduced biofilm formation of C. albicans by >67 %. When live probiotics or their supernatants were overlaid on preformed C. albicans biofilms, biofilm size was reduced by >63 and >65 % respectively. Quantitative real-time PCR results indicated that the combined supernatants of SD5870 and CBS N116411 significantly reduced the expression of several C. albicans genes involved in the yeast-hyphae transition: ALS3 (adhesin/invasin) by 70 % (P < 0.0001), EFG1 (hyphae-specific gene activator) by 47 % (P = 0.0061), SAP5 (secreted protease) by 49 % (P < 0.0001) and HWP1 (hyphal wall protein critical to biofilm formation) by >99 % (P < 0.0001). These findings suggest the combination of L. plantarum SD5870, L. helveticus CBS N116411 and S. salivarius DSM 14685 is effective at both preventing the formation of and removing preformed C. albicans biofilms. Our novel results point to the downregulation of several Candida genes critical to the yeast-hyphae transition, biofilm formation, tissue invasion and cellular damage.}, }
@article {pmid26839074, year = {2016}, author = {Reid, G and Kumar, H and Khan, AI and Rautava, S and Tobin, J and Salminen, S}, title = {The case in favour of probiotics before, during and after pregnancy: insights from the first 1,500 days.}, journal = {Beneficial microbes}, volume = {7}, number = {3}, pages = {353-362}, doi = {10.3920/BM2015.0140}, pmid = {26839074}, issn = {1876-2891}, mesh = {District of Columbia ; Dysbiosis/*prevention &amp; control ; Female ; Humans ; *Infant Health ; Pregnancy ; Pregnancy Complications/*prevention &amp; control ; Probiotics/*administration &amp; dosage ; Treatment Outcome ; United States ; }, abstract = {Successful human reproduction requires microbial homeostasis in the female reproductive tract, and colonisation of the newborn with beneficial microbes. In order to prevent several complications associated with dysbiosis, the administration of probiotics is more often being considered. The objective of the enclosed review was to examine the rationale for probiotic utility before and during pregnancy and in the early phase of infant life. The conclusions emerged from a panel of researchers who met during the International Scientific Association for Probiotics and Prebiotics (ISAPP) workshop held in Washington, DC, USA in 2015. The group concluded based upon the current literature, that a case can be made for the use of a specific sets of probiotic organisms during the first 1,500 days of life, with the goal of a healthy pregnancy to term, and a healthy start to life with lowered risk of infections and inflammatory events. The key to successfully translating these recommendations to practice is that products be made available and affordable to women in developed and developing countries.}, }
@article {pmid26833346, year = {2016}, author = {Jaillard, M and Tournoud, M and Meynier, F and Veyrieras, JB}, title = {Optimization of alignment-based methods for taxonomic binning of metagenomics reads.}, journal = {Bioinformatics (Oxford, England)}, volume = {32}, number = {12}, pages = {1779-1787}, doi = {10.1093/bioinformatics/btw040}, pmid = {26833346}, issn = {1367-4811}, mesh = {Algorithms ; Humans ; Metagenome ; *Metagenomics ; Microbiota ; Models, Theoretical ; }, abstract = {MOTIVATION: Alignment-based taxonomic binning for metagenome characterization proceeds in two steps: reads mapping against a reference database (RDB) and taxonomic assignment according to the best hits. Beyond the sequencing technology and the completeness of the RDB, selecting the optimal configuration of the workflow, in particular the mapper parameters and the best hit selection threshold, to get the highest binning performance remains quite empirical.<br><br>RESULTS: We developed a statistical framework to perform such optimization at a minimal computational cost. Using an optimization experimental design and simulated datasets for three sequencing technologies, we built accurate prediction models for five performance indicators and then derived the parameter configuration providing the optimal performance. Whatever the mapper and the dataset, we observed that the optimal configuration yielded better performance than the default configuration and that the best hit selection threshold had a large impact on performance. Finally, on a reference dataset from the Human Microbiome Project, we confirmed that the optimized configuration increased the performance compared with the default configuration.<br><br>Not applicable.<br><br>CONTACT: magali.dancette@biomerieux.com<br><br>SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.}, }
@article {pmid26828815, year = {2016}, author = {Banjara, N and Nickerson, KW and Suhr, MJ and Hallen-Adams, HE}, title = {Killer toxin from several food-derived Debaryomyces hansenii strains effective against pathogenic Candida yeasts.}, journal = {International journal of food microbiology}, volume = {222}, number = {}, pages = {23-29}, doi = {10.1016/j.ijfoodmicro.2016.01.016}, pmid = {26828815}, issn = {1879-3460}, mesh = {Antibiosis/*physiology ; Candida/*drug effects ; Cheese/microbiology ; *Food Microbiology ; Humans ; Hydrogen-Ion Concentration ; Mycotoxins/*pharmacology ; Saccharomycetales/*chemistry ; Temperature ; }, abstract = {Candida yeasts are the dominant fungi in the healthy human microbiome, but are well-known for causing disease following a variety of perturbations. Evaluation of fungal populations from the healthy human gut revealed a significant negative correlation between the foodborne yeast, Debaryomyces hansenii, and Candida species. D. hansenii is reported to produce killer toxins (mycocins) effective against other yeast species. In order to better understand this phenomenon, a collection of 42 D. hansenii isolates was obtained from 22 cheeses and evaluated for killer activity against Candida albicans and Candida tropicalis over a range of temperatures and pH values. Twenty three strains demonstrated killer activity against both C. albicans and C. tropicalis, which was pH- and temperature-dependent, with no killer activity observed for any strain at pH6.5 or higher, or at ≥ 35 °C (physiological conditions in the human gastrointestinal tract). A cell-free mycocin preparation showed transient killer activity against C. albicans at 35 °C and a cheese sample containing a killer D. hansenii strain demonstrated sustained killer activity against both C. albicans and C. tropicalis. Together, these observations raise the possibility that D. hansenii could influence Candida populations in the gut.}, }
@article {pmid26823997, year = {2016}, author = {Verstraelen, H and Vilchez-Vargas, R and Desimpel, F and Jauregui, R and Vankeirsbilck, N and Weyers, S and Verhelst, R and De Sutter, P and Pieper, DH and Van De Wiele, T}, title = {Characterisation of the human uterine microbiome in non-pregnant women through deep sequencing of the V1-2 region of the 16S rRNA gene.}, journal = {PeerJ}, volume = {4}, number = {}, pages = {e1602}, pmid = {26823997}, issn = {2167-8359}, abstract = {Background. It is widely assumed that the uterine cavity in non-pregnant women is physiologically sterile, also as a premise to the long-held view that human infants develop in a sterile uterine environment, though likely reflecting under-appraisal of the extent of the human bacterial metacommunity. In an exploratory study, we aimed to investigate the putative presence of a uterine microbiome in a selected series of non-pregnant women through deep sequencing of the V1-2 hypervariable region of the 16S ribosomal RNA (rRNA) gene. Methods. Nineteen women with various reproductive conditions, including subfertility, scheduled for hysteroscopy and not showing uterine anomalies were recruited. Subjects were highly diverse with regard to demographic and medical history and included nulliparous and parous women. Endometrial tissue and mucus harvesting was performed by use of a transcervical device designed to obtain endometrial biopsy, while avoiding cervicovaginal contamination. Bacteria were targeted by use of a barcoded Illumina MiSeq paired-end sequencing method targeting the 16S rRNA gene V1-2 region, yielding an average of 41,194 reads per sample after quality filtering. Taxonomic annotation was pursued by comparison with sequences available through the Ribosomal Database Project and the NCBI database. Results. Out of 183 unique 16S rRNA gene amplicon sequences, 15 phylotypes were present in all samples. In some 90% of the women included, community architecture was fairly similar inasmuch B. xylanisolvens, B. thetaiotaomicron, B. fragilis and an undetermined Pelomonas taxon constituted over one third of the endometrial bacterial community. On the singular phylotype level, six women showed predominance of L. crispatus or L. iners in the presence of the Bacteroides core. Two endometrial communities were highly dissimilar, largely lacking the Bacteroides core, one dominated by L. crispatus and another consisting of a highly diverse community, including Prevotella spp., Atopobium vaginae, and Mobiluncus curtisii. Discussion. Our findings are, albeit not necessarily generalizable, consistent with the presence of a unique microbiota dominated by Bacteroides residing on the endometrium of the human non-pregnant uterus. The transcervical sampling approach may be influenced to an unknown extent by endocervical microbiota, which remain uncharacterised, and therefore warrants further validation. Nonetheless, consistent with our understanding of the human microbiome, the uterine microbiota are likely to have a previously unrecognized role in uterine physiology and human reproduction. Further study is therefore warranted to document community ecology and dynamics of the uterine microbiota, as well as the role of the uterine microbiome in health and disease.}, }
@article {pmid26821151, year = {2017}, author = {Thomas, CL and Fernández-Peñas, P}, title = {The microbiome and atopic eczema: More than skin deep.}, journal = {The Australasian journal of dermatology}, volume = {58}, number = {1}, pages = {18-24}, doi = {10.1111/ajd.12435}, pmid = {26821151}, issn = {1440-0960}, mesh = {Dermatitis, Atopic/*microbiology ; Filaggrin Proteins ; Gastrointestinal Microbiome ; Humans ; *Microbiota ; Probiotics ; Respiratory System/microbiology ; Skin/*microbiology ; *Staphylococcus aureus ; Symptom Flare Up ; }, abstract = {Discoveries in the defective molecular composition of the epidermal barrier, such as the epidermal protein filaggrin, in those with atopic eczema (or atopic dermatitis [AD]) have proved crucial in understanding this disease, but its aetiology remains to be fully elucidated. The epidermal barrier is just one interface between the microbial world and our immune system. Recent advances in molecular technology have demonstrated for the first time the true scale of the normal human microbiome and changes seen in disease states. In this review article we discuss the role of the human microbiome in the aetiology and maintenance of AD. The role of Staphylococcus aureus within the skin microbiome is examined, in addition to the role of other bacteria and fungi, identified using novel culture-independent methods. The significant contribution of the gut microbiome and its manipulation via probiotic use is also reviewed. We emphasise that the microbiome of separate systems, including the gut, has a significant role to play in the manifestation of this cutaneous disorder. To date, there has been a lack of studies investigating whether changes to the lung microbiome may play a role in AD. An early interaction between the microbiome and immune system via multiple routes (skin-gut-lung) could feasibly affect the risk of a subsequent development of atopic diseases. When making management decisions for AD patients, clinicians must be mindful of the role of the microbiome.}, }
@article {pmid26819854, year = {2016}, author = {Lewis, ZT and Davis, JC and Smilowitz, JT and German, JB and Lebrilla, CB and Mills, DA}, title = {The impact of freeze-drying infant fecal samples on measures of their bacterial community profiles and milk-derived oligosaccharide content.}, journal = {PeerJ}, volume = {4}, number = {}, pages = {e1612}, pmid = {26819854}, issn = {2167-8359}, support = {R01 AT007079/AT/NCCIH NIH HHS/United States ; R01 AT008759/AT/NCCIH NIH HHS/United States ; R01 HD061923/HD/NICHD NIH HHS/United States ; }, abstract = {Infant fecal samples are commonly studied to investigate the impacts of breastfeeding on the development of the microbiota and subsequent health effects. Comparisons of infants living in different geographic regions and environmental contexts are needed to aid our understanding of evolutionarily-selected milk adaptations. However, the preservation of fecal samples from individuals in remote locales until they can be processed can be a challenge. Freeze-drying (lyophilization) offers a cost-effective way to preserve some biological samples for transport and analysis at a later date. Currently, it is unknown what, if any, biases are introduced into various analyses by the freeze-drying process. Here, we investigated how freeze-drying affected analysis of two relevant and intertwined aspects of infant fecal samples, marker gene amplicon sequencing of the bacterial community and the fecal oligosaccharide profile (undigested human milk oligosaccharides). No differences were discovered between the fecal oligosaccharide profiles of wet and freeze-dried samples. The marker gene sequencing data showed an increase in proportional representation of Bacteriodes and a decrease in detection of bifidobacteria and members of class Bacilli after freeze-drying. This sample treatment bias may possibly be related to the cell morphology of these different taxa (Gram status). However, these effects did not overwhelm the natural variation among individuals, as the community data still strongly grouped by subject and not by freeze-drying status. We also found that compensating for sample concentration during freeze-drying, while not necessary, was also not detrimental. Freeze-drying may therefore be an acceptable method of sample preservation and mass reduction for some studies of microbial ecology and milk glycan analysis.}, }
@article {pmid26812577, year = {2016}, author = {Sohrabi, M and Nair, RG and Samaranayake, LP and Zhang, L and Zulfiker, AH and Ahmetagic, A and Good, D and Wei, MQ}, title = {The yield and quality of cellular and bacterial DNA extracts from human oral rinse samples are variably affected by the cell lysis methodology.}, journal = {Journal of microbiological methods}, volume = {122}, number = {}, pages = {64-72}, doi = {10.1016/j.mimet.2016.01.013}, pmid = {26812577}, issn = {1872-8359}, mesh = {Bacteria/drug effects/*genetics/isolation &amp; purification ; Bacteriological Techniques/methods ; DNA/analysis/chemistry/isolation &amp; purification ; DNA Contamination ; DNA, Bacterial/analysis/*chemistry/genetics/*isolation &amp; purification ; Firmicutes/drug effects/genetics/isolation &amp; purification ; Glyceraldehyde-3-Phosphate Dehydrogenases/genetics ; Humans ; Male ; Microbiota/drug effects/genetics ; Mouth/*microbiology ; Muramidase/chemistry ; RNA, Ribosomal, 16S/genetics ; Real-Time Polymerase Chain Reaction ; Saliva/microbiology ; Serine Endopeptidases/chemistry ; U937 Cells ; Zirconium/chemistry ; }, abstract = {Recent culture-independent studies have enabled detailed mapping of human microbiome that has not been hitherto achievable by culture-based methods. DNA extraction is a key element of bacterial culture-independent studies that critically impacts on the outcome of the detected microbial profile. Despite the variations in DNA extraction methods described in the literature, no standardized technique is available for the purpose of microbiome profiling. Hence, standardization of DNA extraction methods is urgently needed to yield comparable data from different studies. We examined the effect of eight different cell lysis protocols on the yield and quality of the extracted DNA from oral rinse samples. These samples were exposed to cell lysis techniques based on enzymatic, mechanical, and a combination of enzymatic-mechanical methods. The outcome measures evaluated were total bacterial population, Firmicutes levels and human DNA contamination (in terms of surrogate GAPDH levels). We noted that all three parameters were significantly affected by the method of cell lysis employed. Although the highest yield of gDNA was obtained using lysozyme-achromopeptidase method, the lysozyme-zirconium beads method yielded the peak quantity of total bacterial DNA and Firmicutes with a lower degree of GAPDH contamination compared with the other methods. Taken together our data clearly points to an urgent need for a consensus, standardized DNA extraction technique to evaluate the oral microbiome using oral rinse samples. Further, if Firmicutes levels are the focus of investigation in oral rinse microbiome analyses then the lysozyme-zirconium bead method would be the method of choice in preference to others.}, }
@article {pmid26794165, year = {2016}, author = {O'Doherty, KC and Virani, A and Wilcox, ES}, title = {The Human Microbiome and Public Health: Social and Ethical Considerations.}, journal = {American journal of public health}, volume = {106}, number = {3}, pages = {414-420}, pmid = {26794165}, issn = {1541-0048}, mesh = {Anti-Bacterial Agents/adverse effects ; Culture ; Delivery, Obstetric/methods ; Diet ; *Environment ; *Ethics, Research ; *Health Status ; Humans ; Immune System/microbiology ; Infant, Newborn ; *Microbiota ; Obesity/microbiology ; Probiotics/therapeutic use ; Public Health ; *Social Environment ; }, abstract = {Rapid advances in human microbiome research point to an increasing range of health outcomes related to the composition of an individual's microbiome. To date, much research has focused on individual health, with a paucity of attention to public health implications. This is a critical oversight owing to the potentially shared nature of the human microbiome across communities and vertical and horizontal mechanisms for transferring microbiomes among humans. We explored some key ethical and social implications of human microbiome research for public health. We focused on (1) insights from microbiome research about damage to individual and shared microbiomes from prevalent societal practices, and (2) ethical and social implications of novel technologies developed on the basis of emerging microbiome science.}, }
@article {pmid26793178, year = {2015}, author = {Francino, MP}, title = {Antibiotics and the Human Gut Microbiome: Dysbioses and Accumulation of Resistances.}, journal = {Frontiers in microbiology}, volume = {6}, number = {}, pages = {1543}, pmid = {26793178}, issn = {1664-302X}, abstract = {The human microbiome is overly exposed to antibiotics, due, not only to their medical use, but also to their utilization in farm animals and crops. Microbiome composition can be rapidly altered by exposure to antibiotics, with potential immediate effects on health, for instance through the selection of resistant opportunistic pathogens that can cause acute disease. Microbiome alterations induced by antibiotics can also indirectly affect health in the long-term. The mutualistic microbes in the human body interact with many physiological processes, and participate in the regulation of immune and metabolic homeostasis. Therefore, antibiotic exposure can alter many basic physiological equilibria, promoting long-term disease. In addition, excessive antibiotic use fosters bacterial resistance, and the overly exposed human microbiome has become a significant reservoir of resistance genes, contributing to the increasing difficulty in controlling bacterial infections. Here, the complex relationships between antibiotics and the human microbiome are reviewed, with focus on the intestinal microbiota, addressing (1) the effects of antibiotic use on the composition and function of the gut microbiota, (2) the impact of antibiotic-induced microbiota alterations on immunity, metabolism, and health, and (3) the role of the gut microbiota as a reservoir of antibiotic resistances.}, }
@article {pmid26789414, year = {2016}, author = {Bresciani, A and Paul, S and Schommer, N and Dillon, MB and Bancroft, T and Greenbaum, J and Sette, A and Nielsen, M and Peters, B}, title = {T-cell recognition is shaped by epitope sequence conservation in the host proteome and microbiome.}, journal = {Immunology}, volume = {148}, number = {1}, pages = {34-39}, pmid = {26789414}, issn = {1365-2567}, support = {HHSN272201200010C/AI/NIAID NIH HHS/United States ; }, mesh = {Amino Acid Sequence ; Conserved Sequence ; Epitopes, T-Lymphocyte/*immunology ; *Gastrointestinal Microbiome ; Humans ; *Proteome ; T-Lymphocytes/*immunology ; }, abstract = {Several mechanisms exist to avoid or suppress inflammatory T-cell immune responses that could prove harmful to the host due to targeting self-antigens or commensal microbes. We hypothesized that these mechanisms could become evident when comparing the immunogenicity of a peptide from a pathogen or allergen with the conservation of its sequence in the human proteome or the healthy human microbiome. Indeed, performing such comparisons on large sets of validated T-cell epitopes, we found that epitopes that are similar with self-antigens above a certain threshold showed lower immunogenicity, presumably as a result of negative selection of T cells capable of recognizing such peptides. Moreover, we also found a reduced level of immune recognition for epitopes conserved in the commensal microbiome, presumably as a result of peripheral tolerance. These findings indicate that the existence (and potentially the polarization) of T-cell responses to a given epitope is influenced and to some extent predictable based on its similarity to self-antigens and commensal antigens.}, }
@article {pmid26788878, year = {2016}, author = {Agler, MT and Ruhe, J and Kroll, S and Morhenn, C and Kim, ST and Weigel, D and Kemen, EM}, title = {Microbial Hub Taxa Link Host and Abiotic Factors to Plant Microbiome Variation.}, journal = {PLoS biology}, volume = {14}, number = {1}, pages = {e1002352}, pmid = {26788878}, issn = {1545-7885}, mesh = {Arabidopsis/genetics/*microbiology ; Bacteria ; Basidiomycota/physiology ; Endophytes/physiology ; *Microbiota ; Oomycetes/physiology ; }, abstract = {Plant-associated microorganisms have been shown to critically affect host physiology and performance, suggesting that evolution and ecology of plants and animals can only be understood in a holobiont (host and its associated organisms) context. Host-associated microbial community structures are affected by abiotic and host factors, and increased attention is given to the role of the microbiome in interactions such as pathogen inhibition. However, little is known about how these factors act on the microbial community, and especially what role microbe-microbe interaction dynamics play. We have begun to address this knowledge gap for phyllosphere microbiomes of plants by simultaneously studying three major groups of Arabidopsis thaliana symbionts (bacteria, fungi and oomycetes) using a systems biology approach. We evaluated multiple potential factors of microbial community control: we sampled various wild A. thaliana populations at different times, performed field plantings with different host genotypes, and implemented successive host colonization experiments under lab conditions where abiotic factors, host genotype, and pathogen colonization was manipulated. Our results indicate that both abiotic factors and host genotype interact to affect plant colonization by all three groups of microbes. Considering microbe-microbe interactions, however, uncovered a network of interkingdom interactions with significant contributions to community structure. As in other scale-free networks, a small number of taxa, which we call microbial "hubs," are strongly interconnected and have a severe effect on communities. By documenting these microbe-microbe interactions, we uncover an important mechanism explaining how abiotic factors and host genotypic signatures control microbial communities. In short, they act directly on "hub" microbes, which, via microbe-microbe interactions, transmit the effects to the microbial community. We analyzed two "hub" microbes (the obligate biotrophic oomycete pathogen Albugo and the basidiomycete yeast fungus Dioszegia) more closely. Albugo had strong effects on epiphytic and endophytic bacterial colonization. Specifically, alpha diversity decreased and beta diversity stabilized in the presence of Albugo infection, whereas they otherwise varied between plants. Dioszegia, on the other hand, provided evidence for direct hub interaction with phyllosphere bacteria. The identification of microbial "hubs" and their importance in phyllosphere microbiome structuring has crucial implications for plant-pathogen and microbe-microbe research and opens new entry points for ecosystem management and future targeted biocontrol. The revelation that effects can cascade through communities via "hub" microbes is important to understand community structure perturbations in parallel fields including human microbiomes and bioprocesses. In particular, parallels to human microbiome "keystone" pathogens and microbes open new avenues of interdisciplinary research that promise to better our understanding of functions of host-associated microbiomes.}, }
@article {pmid26778967, year = {2015}, author = {Savidge, TC}, title = {Epigenetic Regulation of Enteric Neurotransmission by Gut Bacteria.}, journal = {Frontiers in cellular neuroscience}, volume = {9}, number = {}, pages = {503}, pmid = {26778967}, issn = {1662-5102}, support = {P30 DK056338/DK/NIDDK NIH HHS/United States ; R01 AI100914/AI/NIAID NIH HHS/United States ; R21 DK096323/DK/NIDDK NIH HHS/United States ; }, abstract = {The Human Microbiome Project defined microbial community interactions with the human host, and provided important molecular insight into how epigenetic factors can influence intestinal ecosystems. Given physiological context, changes in gut microbial community structure are increasingly found to associate with alterations in enteric neurotransmission and disease. At present, it is not known whether shifts in microbial community dynamics represent cause or consequence of disease pathogenesis. The discovery of bacterial-derived neurotransmitters suggests further studies are needed to establish their role in enteric neuropathy. This mini-review highlights recent advances in bacterial communications to the autonomic nervous system and discusses emerging epigenetic data showing that diet, probiotic and antibiotic use may regulate enteric neurotransmission through modulation of microbial communities. A particular emphasis is placed on bacterial metabolite regulation of enteric nervous system function in the intestine.}, }
@article {pmid26776185, year = {2016}, author = {Callahan, B and Proctor, D and Relman, D and Fukuyama, J and Holmes, S}, title = {REPRODUCIBLE RESEARCH WORKFLOW IN R FOR THE ANALYSIS OF PERSONALIZED HUMAN MICROBIOME DATA.}, journal = {Pacific Symposium on Biocomputing. Pacific Symposium on Biocomputing}, volume = {21}, number = {}, pages = {183-194}, pmid = {26776185}, issn = {2335-6936}, support = {R01 GM086884/GM/NIGMS NIH HHS/United States ; R01AI112401/AI/NIAID NIH HHS/United States ; R01GM099534/GM/NIGMS NIH HHS/United States ; R01 DE023113/DE/NIDCR NIH HHS/United States ; T32 AI007328/AI/NIAID NIH HHS/United States ; R01 AI112401/AI/NIAID NIH HHS/United States ; R01 GM099534/GM/NIGMS NIH HHS/United States ; R01DE023113/DE/NIDCR NIH HHS/United States ; }, mesh = {Computational Biology/methods/statistics &amp; numerical data ; Data Interpretation, Statistical ; Female ; High-Throughput Nucleotide Sequencing/statistics &amp; numerical data ; Humans ; Longitudinal Studies ; Microbial Consortia/genetics ; *Microbiota/genetics ; Mouth/microbiology ; Precision Medicine/*statistics &amp; numerical data ; Pregnancy ; Principal Component Analysis ; Reproducibility of Results ; Sequence Analysis, DNA/statistics &amp; numerical data ; *Software ; Vagina/microbiology ; Workflow ; }, abstract = {This article presents a reproducible research workflow for amplicon-based microbiome studies in personalized medicine created using Bioconductor packages and the knitr markdown interface.We show that sometimes a multiplicity of choices and lack of consistent documentation at each stage of the sequential processing pipeline used for the analysis of microbiome data can lead to spurious results. We propose its replacement with reproducible and documented analysis using R packages dada2, knitr, and phyloseq. This workflow implements both key stages of amplicon analysis: the initial filtering and denoising steps needed to construct taxonomic feature tables from error-containing sequencing reads (dada2), and the exploratory and inferential analysis of those feature tables and associated sample metadata (phyloseq). This workow facilitates reproducible interrogation of the full set of choices required in microbiome studies. We present several examples in which we leverage existing packages for analysis in a way that allows easy sharing and modification by others, and give pointers to articles that depend on this reproducible workflow for the study of longitudinal and spatial series analyses of the vaginal microbiome in pregnancy and the oral microbiome in humans with healthy dentition and intra-oral tissues.}, }
@article {pmid28848868, year = {2016}, author = {Gates, K and Martinez, F}, title = {The Human Microbiome in the Lung: Are Infections Contributing to Lung Health and Disease?.}, journal = {Chronic obstructive pulmonary diseases (Miami, Fla.)}, volume = {3}, number = {1}, pages = {466-472}, pmid = {28848868}, issn = {2372-952X}, abstract = {This article serves as a CME-available, enduring material summary of the following COPD9USA presentations: "The Human Microbiome in the Lung: The Way Forward" Presenter: Gary B. Huffnagle, PhD "COPD: Is it Just Bacteria?" Presenter: Alison Morris, MD, MS "What We Have Learned From Other Disease States and How It Applies to COPD" Presenter: Fernando Martinez, MD, MS.}, }
@article {pmid26764593, year = {2016}, author = {Zmora, N and Zeevi, D and Korem, T and Segal, E and Elinav, E}, title = {Taking it Personally: Personalized Utilization of the Human Microbiome in Health and Disease.}, journal = {Cell host &amp; microbe}, volume = {19}, number = {1}, pages = {12-20}, doi = {10.1016/j.chom.2015.12.016}, pmid = {26764593}, issn = {1934-6069}, mesh = {Bacteria/classification/genetics/isolation &amp; purification ; *Gastrointestinal Microbiome ; Gastrointestinal Tract/metabolism/microbiology ; Humans ; Precision Medicine/methods/*trends ; }, abstract = {The genomic revolution enabled the clinical inclusion of an immense body of person-specific information to an extent that is revolutionizing medicine and science. The gut microbiome, our "second genome," dynamically integrates signals from the host and its environment, impacting health and risk of disease. Herein, we summarize how individualized characterization of the microbiome composition and function may assist in personalized diagnostic assessment, risk stratification, disease prevention, treatment decision-making, and patients' follow up. We further discuss the limitations, pitfalls, and challenges that the microbiome field faces in integrating patient-specific microbial data into the clinical realm. Finally, we highlight how recent insights into personalized modulation of the microbiome, by nutritional and pre-, pro-, and post-biotic intervention, may lead to development of individualized approaches that may enable us to harness the microbiome as a central precision medicine target.}, }
@article {pmid26733066, year = {2016}, author = {Bomar, L and Brugger, SD and Yost, BH and Davies, SS and Lemon, KP}, title = {Corynebacterium accolens Releases Antipneumococcal Free Fatty Acids from Human Nostril and Skin Surface Triacylglycerols.}, journal = {mBio}, volume = {7}, number = {1}, pages = {e01725-15}, pmid = {26733066}, issn = {2150-7511}, support = {R01 AI101018/AI/NIAID NIH HHS/United States ; DE020751/DE/NIDCR NIH HHS/United States ; AI101018/AI/NIAID NIH HHS/United States ; R01 AT007830/AT/NCCIH NIH HHS/United States ; AI066304/AI/NIAID NIH HHS/United States ; R01 AI066304/AI/NIAID NIH HHS/United States ; UL1 RR025758/RR/NCRR NIH HHS/United States ; DE007327/DE/NIDCR NIH HHS/United States ; 1 UL1 RR025758-02/RR/NCRR NIH HHS/United States ; AT007830/AT/NCCIH NIH HHS/United States ; P30 DE020751/DE/NIDCR NIH HHS/United States ; T32 DE007327/DE/NIDCR NIH HHS/United States ; }, mesh = {Anti-Bacterial Agents/pharmacology ; *Antibiosis ; Carrier State/microbiology ; Child ; Child, Preschool ; Corynebacterium/chemistry/*metabolism ; Fatty Acids, Nonesterified/*metabolism/pharmacology ; Humans ; Hydrolysis ; Infant ; Microbiota ; Nasal Cavity/*microbiology ; Pneumococcal Infections/prevention &amp; control ; Skin/*microbiology ; Streptococcus pneumoniae/drug effects/growth &amp; development/*physiology ; Triglycerides/*metabolism ; Triolein/metabolism ; }, abstract = {UNLABELLED: Bacterial interspecies interactions play clinically important roles in shaping microbial community composition. We observed that Corynebacterium spp. are overrepresented in children free of Streptococcus pneumoniae (pneumococcus), a common pediatric nasal colonizer and an important infectious agent. Corynebacterium accolens, a benign lipid-requiring species, inhibits pneumococcal growth during in vitro cocultivation on medium supplemented with human skin surface triacylglycerols (TAGs) that are likely present in the nostrils. This inhibition depends on LipS1, a TAG lipase necessary for C. accolens growth on TAGs such as triolein. We determined that C. accolens hydrolysis of triolein releases oleic acid, which inhibits pneumococcus, as do other free fatty acids (FFAs) that might be released by LipS1 from human skin surface TAGs. Our results support a model in which C. accolens hydrolyzes skin surface TAGS in vivo releasing antipneumococcal FFAs. These data indicate that C. accolens may play a beneficial role in sculpting the human microbiome.<br><br>IMPORTANCE: Little is known about how harmless Corynebacterium species that colonize the human nose and skin might impact pathogen colonization and proliferation at these sites. We show that Corynebacterium accolens, a common benign nasal bacterium, modifies its local habitat in vitro as it inhibits growth of Streptococcus pneumoniae by releasing antibacterial free fatty acids from host skin surface triacylglycerols. We further identify the primary C.&#xa0;accolens lipase required for this activity. We postulate a model in which higher numbers of C.&#xa0;accolens cells deter/limit S.&#xa0;pneumoniae nostril colonization, which might partly explain why children without S.&#xa0;pneumoniae colonization have higher levels of nasal Corynebacterium. This work narrows the gap between descriptive studies and the needed in-depth understanding of the molecular mechanisms of microbe-microbe interactions that help shape the human microbiome. It also lays the foundation for future in vivo studies to determine whether habitat modification by C.&#xa0;accolens could be promoted to control pathogen colonization.}, }
@article {pmid26730578, year = {2016}, author = {Vogtmann, E and Goedert, JJ}, title = {Epidemiologic studies of the human microbiome and cancer.}, journal = {British journal of cancer}, volume = {114}, number = {3}, pages = {237-242}, pmid = {26730578}, issn = {1532-1827}, support = {ZIA CP010214/ImNIH/Intramural NIH HHS/United States ; ZIA-CP-010214/CP/NCI NIH HHS/United States ; }, mesh = {Bacterial Infections/epidemiology/*microbiology ; Carrier State/epidemiology/*microbiology ; Epidemiologic Studies ; High-Throughput Nucleotide Sequencing ; Humans ; Microbiota/*genetics ; Neoplasms/epidemiology/*microbiology ; Risk Factors ; }, abstract = {The human microbiome, which includes the collective genome of all bacteria, archaea, fungi, protists, and viruses found in and on the human body, is altered in many diseases and may substantially affect cancer risk. Previously detected associations of individual bacteria (e.g., Helicobacter pylori), periodontal disease, and inflammation with specific cancers have motivated studies considering the association between the human microbiome and cancer risk. This short review summarises microbiome research, focusing on published epidemiological associations with gastric, oesophageal, hepatobiliary, pancreatic, lung, colorectal, and other cancers. Large, prospective studies of the microbiome that employ multidisciplinary laboratory and analysis methods, as well as rigorous validation of case status, are likely to yield translational opportunities to reduce cancer morbidity and mortality by improving prevention, screening, and treatment.}, }
@article {pmid26718401, year = {2016}, author = {Ranjan, R and Rani, A and Metwally, A and McGee, HS and Perkins, DL}, title = {Analysis of the microbiome: Advantages of whole genome shotgun versus 16S amplicon sequencing.}, journal = {Biochemical and biophysical research communications}, volume = {469}, number = {4}, pages = {967-977}, pmid = {26718401}, issn = {1090-2104}, support = {R01 AI053878/AI/NIAID NIH HHS/United States ; R01 HL081663/HL/NHLBI NIH HHS/United States ; }, mesh = {Bacteria/classification/genetics/isolation &amp; purification ; Base Sequence ; Chromosome Mapping/*methods ; DNA, Bacterial/*genetics ; Humans ; Metagenome/*genetics ; Microbiota/*genetics ; Molecular Sequence Data ; RNA, Ribosomal, 16S/*genetics ; Reproducibility of Results ; Sensitivity and Specificity ; Sequence Analysis, DNA/*methods ; }, abstract = {The human microbiome has emerged as a major player in regulating human health and disease. Translational studies of the microbiome have the potential to indicate clinical applications such as fecal transplants and probiotics. However, one major issue is accurate identification of microbes constituting the microbiota. Studies of the microbiome have frequently utilized sequencing of the conserved 16S ribosomal RNA (rRNA) gene. We present a comparative study of an alternative approach using whole genome shotgun sequencing (WGS). In the present study, we analyzed the human fecal microbiome compiling a total of 194.1 × 10(6) reads from a single sample using multiple sequencing methods and platforms. Specifically, after establishing the reproducibility of our methods with extensive multiplexing, we compared: 1) The 16S rRNA amplicon versus the WGS method, 2) the Illumina HiSeq versus MiSeq platforms, 3) the analysis of reads versus de novo assembled contigs, and 4) the effect of shorter versus longer reads. Our study demonstrates that whole genome shotgun sequencing has multiple advantages compared with the 16S amplicon method including enhanced detection of bacterial species, increased detection of diversity and increased prediction of genes. In addition, increased length, either due to longer reads or the assembly of contigs, improved the accuracy of species detection.}, }
@article {pmid26712937, year = {2015}, author = {Abdul Halim, MF and Karch, KR and Zhou, Y and Haft, DH and Garcia, BA and Pohlschroder, M}, title = {Permuting the PGF Signature Motif Blocks both Archaeosortase-Dependent C-Terminal Cleavage and Prenyl Lipid Attachment for the Haloferax volcanii S-Layer Glycoprotein.}, journal = {Journal of bacteriology}, volume = {198}, number = {5}, pages = {808-815}, pmid = {26712937}, issn = {1098-5530}, support = {T32 GM071339/GM/NIGMS NIH HHS/United States ; }, mesh = {Amino Acid Motifs ; Archaeal Proteins/chemistry/genetics/*metabolism ; Cell Membrane ; Gene Expression Regulation, Archaeal/physiology ; Gene Expression Regulation, Enzymologic/physiology ; Glycine/chemistry ; Haloferax volcanii/cytology/genetics/*metabolism ; Lipid Metabolism ; Lipids/*chemistry ; Membrane Glycoproteins/genetics/*metabolism ; Peptide Hydrolases/*metabolism ; Phenylalanine/chemistry ; Proline/chemistry ; }, abstract = {UNLABELLED: For years, the S-layer glycoprotein (SLG), the sole component of many archaeal cell walls, was thought to be anchored to the cell surface by a C-terminal transmembrane segment. Recently, however, we demonstrated that the Haloferax volcanii SLG C terminus is removed by an archaeosortase (ArtA), a novel peptidase. SLG, which was previously shown to be lipid modified, contains a C-terminal tripartite structure, including a highly conserved proline-glycine-phenylalanine (PGF) motif. Here, we demonstrate that ArtA does not process an SLG variant where the PGF motif is replaced with a PFG motif (slg(G796F,F797G)). Furthermore, using radiolabeling, we show that SLG lipid modification requires the PGF motif and is ArtA dependent, lending confirmation to the use of a novel C-terminal lipid-mediated protein-anchoring mechanism by prokaryotes. Similar to the case for the ΔartA strain, the growth, cellular morphology, and cell wall of the slg(G796F,F797G) strain, in which modifications of additional H. volcanii ArtA substrates should not be altered, are adversely affected, demonstrating the importance of these posttranslational SLG modifications. Our data suggest that ArtA is either directly or indirectly involved in a novel proteolysis-coupled, covalent lipid-mediated anchoring mechanism. Given that archaeosortase homologs are encoded by a broad range of prokaryotes, it is likely that this anchoring mechanism is widely conserved.<br><br>IMPORTANCE: Prokaryotic proteins bound to cell surfaces through intercalation, covalent attachment, or protein-protein interactions play critical roles in essential cellular processes. Unfortunately, the molecular mechanisms that anchor proteins to archaeal cell surfaces remain poorly characterized. Here, using the archaeon H. volcanii as a model system, we report the first in vivo studies of a novel protein-anchoring pathway involving lipid modification of a peptidase-processed C terminus. Our findings not only yield important insights into poorly understood aspects of archaeal biology but also have important implications for key bacterial species, including those of the human microbiome. Additionally, insights may facilitate industrial applications, given that photosynthetic cyanobacteria encode uncharacterized homologs of this evolutionarily conserved enzyme, or may spur development of unique drug delivery systems.}, }
@article {pmid26711314, year = {2016}, author = {Hoashi, M and Meche, L and Mahal, LK and Bakacs, E and Nardella, D and Naftolin, F and Bar-Yam, N and Dominguez-Bello, MG}, title = {Human Milk Bacterial and Glycosylation Patterns Differ by Delivery Mode.}, journal = {Reproductive sciences (Thousand Oaks, Calif.)}, volume = {23}, number = {7}, pages = {902-907}, doi = {10.1177/1933719115623645}, pmid = {26711314}, issn = {1933-7205}, mesh = {Cesarean Section ; Cross-Sectional Studies ; Delivery, Obstetric ; Female ; Glycosylation ; Humans ; Microbiota ; Milk, Human/*metabolism/*microbiology ; }, abstract = {Mammals have evolved to nourish their offspring exclusively with maternal milk for around half of the lactation period, a crucial developmental window. In view of oral-breast contact during lactation and the differences in oral microbiota between cesarean section (C-section) and vaginally delivered infants, we expected differences in milk composition by delivery mode. We performed a cross-sectional study of banked human milk and found changes related to time since delivery in bacterial abundance and glycosylation patterns only in milk from women who delivered vaginally. The results warrant further research into the effects of delivery mode on milk microbes, milk glycosylation, and postpartum infant development.}, }
@article {pmid26704067, year = {2016}, author = {Parente, E and Cocolin, L and De Filippis, F and Zotta, T and Ferrocino, I and O'Sullivan, O and Neviani, E and De Angelis, M and Cotter, PD and Ercolini, D}, title = {FoodMicrobionet: A database for the visualisation and exploration of food bacterial communities based on network analysis.}, journal = {International journal of food microbiology}, volume = {219}, number = {}, pages = {28-37}, doi = {10.1016/j.ijfoodmicro.2015.12.001}, pmid = {26704067}, issn = {1879-3460}, mesh = {Animals ; DNA Primers/genetics ; DNA, Bacterial/genetics ; *Databases, Genetic ; Food Microbiology/*methods ; Foodborne Diseases/*microbiology ; Humans ; Limit of Detection ; Meat/microbiology ; Microbiota/*genetics ; Milk/microbiology ; RNA, Ribosomal, 16S/genetics ; Real-Time Polymerase Chain Reaction ; Sensitivity and Specificity ; Software ; Vegetable Products/microbiology ; }, abstract = {Amplicon targeted high-throughput sequencing has become a popular tool for the culture-independent analysis of microbial communities. Although the data obtained with this approach are portable and the number of sequences available in public databases is increasing, no tool has been developed yet for the analysis and presentation of data obtained in different studies. This work describes an approach for the development of a database for the rapid exploration and analysis of data on food microbial communities. Data from seventeen studies investigating the structure of bacterial communities in dairy, meat, sourdough and fermented vegetable products, obtained by 16S rRNA gene targeted high-throughput sequencing, were collated and analysed using Gephi, a network analysis software. The resulting database, which we named FoodMicrobionet, was used to analyse nodes and network properties and to build an interactive web-based visualisation. The latter allows the visual exploration of the relationships between Operational Taxonomic Units (OTUs) and samples and the identification of core- and sample-specific bacterial communities. It also provides additional search tools and hyperlinks for the rapid selection of food groups and OTUs and for rapid access to external resources (NCBI taxonomy, digital versions of the original articles). Microbial interaction network analysis was carried out using CoNet on datasets extracted from FoodMicrobionet: the complexity of interaction networks was much lower than that found for other bacterial communities (human microbiome, soil and other environments). This may reflect both a bias in the dataset (which was dominated by fermented foods and starter cultures) and the lower complexity of food bacterial communities. Although some technical challenges exist, and are discussed here, the net result is a valuable tool for the exploration of food bacterial communities by the scientific community and food industry.}, }
@article {pmid26700443, year = {2016}, author = {Rogers, GB and Wesselingh, S}, title = {Precision respiratory medicine and the microbiome.}, journal = {The Lancet. Respiratory medicine}, volume = {4}, number = {1}, pages = {73-82}, doi = {10.1016/S2213-2600(15)00476-2}, pmid = {26700443}, issn = {2213-2619}, mesh = {Humans ; Lung/*microbiology ; Lung Diseases/microbiology/*therapy ; *Microbiota ; *Precision Medicine ; *Pulmonary Medicine ; Respiratory System/microbiology ; Translational Research, Biomedical ; }, abstract = {A decade of rapid technological advances has provided an exciting opportunity to incorporate information relating to a range of potentially important disease determinants in the clinical decision-making process. Access to highly detailed data will enable respiratory medicine to evolve from one-size-fits-all models of care, which are associated with variable clinical effectiveness and high rates of side-effects, to precision approaches, where treatment is tailored to individual patients. The human microbiome has increasingly been recognised as playing an important part in determining disease course and response to treatment. Its inclusion in precision models of respiratory medicine, therefore, is essential. Analysis of the microbiome provides an opportunity to develop novel prognostic markers for airways disease, improve definition of clinical phenotypes, develop additional guidance to aid treatment selection, and increase the accuracy of indicators of treatment effect. In this Review we propose that collaboration between researchers and clinicians is needed if respiratory medicine is to replicate the successes of precision medicine seen in other clinical specialties.}, }
@article {pmid26692900, year = {2015}, author = {Liu, Z and Lin, S and Piantadosi, S}, title = {Network construction and structure detection with metagenomic count data.}, journal = {BioData mining}, volume = {8}, number = {}, pages = {40}, pmid = {26692900}, issn = {1756-0381}, support = {UL1 TR000124/TR/NCATS NIH HHS/United States ; }, abstract = {BACKGROUND: The human microbiome plays a critical role in human health. Massive amounts of metagenomic data have been generated with advances in next-generation sequencing technologies that characterize microbial communities via direct isolation and sequencing. How to extract, analyze, and transform these vast amounts of data into useful knowledge is a great challenge to bioinformaticians. Microbial biodiversity research has focused primarily on taxa composition and abundance and less on the co-occurrences among different taxa. However, taxa co-occurrences and their relationships to environmental and clinical conditions are important because network structure may help to understand how microbial taxa function together.<br><br>RESULTS: We propose a systematic robust approach for bacteria network construction and structure detection using metagenomic count data. Pairwise similarity/distance measures between taxa are proposed by adapting distance measures for samples in ecology. We also extend the sparse inverse covariance approach to a sparse inverse of a similarity matrix from count data for network construction. Our approach is efficient for large metagenomic count data with thousands of bacterial taxa. We evaluate our method with real and simulated data. Our method identifies true and biologically significant network structures efficiently.<br><br>CONCLUSIONS: Network analysis is crucial for detecting subnetwork structures with metagenomic count data. We developed a software tool in MATLAB for network construction and biologically significant module detection. Software MetaNet can be downloaded from http://biostatistics.csmc.edu/MetaNet/.}, }
@article {pmid26674771, year = {2015}, author = {Hoisington, AJ and Brenner, LA and Kinney, KA and Postolache, TT and Lowry, CA}, title = {The microbiome of the built environment and mental health.}, journal = {Microbiome}, volume = {3}, number = {}, pages = {60}, pmid = {26674771}, issn = {2049-2618}, mesh = {Environment Design ; *Environment, Controlled ; Humans ; Inflammation/etiology/microbiology/psychology ; *Mental Health ; *Microbiota ; Sick Building Syndrome/etiology ; }, abstract = {The microbiome of the built environment (MoBE) is a relatively new area of study. While some knowledge has been gained regarding impacts of the MoBE on the human microbiome and disease vulnerability, there is little knowledge of the impacts of the MoBE on mental health. Depending on the specific microbial species involved, the transfer of microorganisms from the built environment to occupant's cutaneous or mucosal membranes has the potential to increase or disrupt immunoregulation and/or exaggerate or suppress inflammation. Preclinical evidence highlighting the influence of the microbiota on systemic inflammation supports the assertion that microorganisms, including those originating from the built environment, have the potential to either increase or decrease the risk of inflammation-induced psychiatric conditions and their symptom severity. With advanced understanding of both the ecology of the built environment, and its influence on the human microbiome, it may be possible to develop bioinformed strategies for management of the built environment to promote mental health. Here we present a brief summary of microbiome research in both areas and highlight two interdependencies including the following: (1) effects of the MoBE on the human microbiome and (2) potential opportunities for manipulation of the MoBE in order to improve mental health. In addition, we propose future research directions including strategies for assessment of changes in the microbiome of common areas of built environments shared by multiple human occupants, and associated cohort-level changes in the mental health of those who spend time in the buildings. Overall, our understanding of the fields of both the MoBE and influence of host-associated microorganisms on mental health are advancing at a rapid pace and, if linked, could offer considerable benefit to health and wellness.}, }
@article {pmid26664362, year = {2015}, author = {Riiser, A}, title = {The human microbiome, asthma, and allergy.}, journal = {Allergy, asthma, and clinical immunology : official journal of the Canadian Society of Allergy and Clinical Immunology}, volume = {11}, number = {}, pages = {35}, pmid = {26664362}, issn = {1710-1484}, abstract = {The human microbiome can be defined as the microorganisms that reside within and on our bodies and how they interact with the environment. Recent research suggests that numerous mutually beneficial interactions occur between a human and their microbiome, including those that are essential for good health. Modern microbiological detection techniques have contributed to new knowledge about microorganisms in their human environment. These findings reveal that the microbiomes of the lung and gut contribute to the pathogenesis of asthma and allergy. For example, evidence indicates that the microbiome of the gut regulates the activities of helper T cell subsets (Th1 and Th2) that affect the development of immune tolerance. Moreover, recent studies demonstrate differences between the lung microbiomes of healthy and asthmatic subjects. The hygiene and biodiversity hypotheses explain how exposure to microorganisms is associated with asthma and allergy. Although those living in developed countries are exposed to fewer and less diverse microorganisms compared with the inhabitants of developing countries, they are experiencing an increase in the incidence of asthma and allergies. Detailed analyses of the human microbiome, as are being conducted under the auspices of the Human Microbiome Project initiated in 2007, promise to contribute insights into the mechanisms and factors that cause asthma and allergy that may lead to the development of strategies to prevent and treat these diseases.}, }
@article {pmid26660761, year = {2016}, author = {Althani, AA and Marei, HE and Hamdi, WS and Nasrallah, GK and El Zowalaty, ME and Al Khodor, S and Al-Asmakh, M and Abdel-Aziz, H and Cenciarelli, C}, title = {Human Microbiome and its Association With Health and Diseases.}, journal = {Journal of cellular physiology}, volume = {231}, number = {8}, pages = {1688-1694}, doi = {10.1002/jcp.25284}, pmid = {26660761}, issn = {1097-4652}, mesh = {*Bacteria/classification/genetics/growth &amp; development/pathogenicity ; Digestive System Diseases/microbiology/virology ; Disease Susceptibility ; *Dysbiosis/microbiology/virology ; *Fungi/classification/genetics/growth &amp; development/pathogenicity ; *Health Status ; Host-Pathogen Interactions ; Humans ; Metabolic Diseases/microbiology/virology ; *Microbiota ; Neurodegenerative Diseases/microbiology/virology ; Risk Factors ; *Viruses/classification/genetics/growth &amp; development/pathogenicity ; }, abstract = {Human microbiota are distinct communities of microorganisms that resides at different body niches. Exploration of the human microbiome has become a reality due to the availability of powerful metagenomics and metatranscriptomic analysis technologies. Recent advances in sequencing and bioinformatics over the past decade help provide a deep insight into the nature of the host-microbial interactions and identification of potential deriver genes and pathways associated with human health, well-being, and predisposition to different diseases. In the present review, we outline recent studies devoted to elucidate the possible link between the microbiota and various type of diseases. The present review also highlights the potential utilization of microbiota as a potential therapeutic option to treat a wide array of human diseases. J. Cell. Physiol. 231: 1688-1694, 2016. © 2015 Wiley Periodicals, Inc.}, }
@article {pmid26659594, year = {2015}, author = {Deusch, O and O'Flynn, C and Colyer, A and Swanson, KS and Allaway, D and Morris, P}, title = {A Longitudinal Study of the Feline Faecal Microbiome Identifies Changes into Early Adulthood Irrespective of Sexual Development.}, journal = {PloS one}, volume = {10}, number = {12}, pages = {e0144881}, pmid = {26659594}, issn = {1932-6203}, mesh = {Animals ; Bifidobacterium/genetics/isolation &amp; purification ; Cats ; Cohort Studies ; DNA, Bacterial/analysis/chemistry ; Diet ; Dogs ; Feces/*microbiology ; Female ; High-Throughput Nucleotide Sequencing ; Lactobacillus/genetics/isolation &amp; purification ; Longitudinal Studies ; Male ; *Microbiota ; Principal Component Analysis ; Sequence Analysis, DNA ; Sexual Development ; }, abstract = {Companion animals provide an excellent model for studies of the gut microbiome because potential confounders such as diet and environment can be more readily controlled for than in humans. Additionally, domestic cats and dogs are typically neutered early in life, enabling an investigation into the potential effect of sex hormones on the microbiome. In a longitudinal study to investigate the potential effects of neutering, neutering age and gender on the gut microbiome during growth, the faeces of kittens (16 male, 14 female) were sampled at 18, 30 and 42 weeks of age. DNA was shotgun sequenced on the Illumina platform and sequence reads were annotated for taxonomy and function by comparison to a database of protein coding genes. In a statistical analysis of diversity, taxonomy and functional potential of the microbiomes, age was identified as the only factor with significant associations. No significant effects were detected for gender, neutering, or age when neutered (19 or 31 weeks). At 18 weeks of age the microbiome was dominated by the genera Lactobacillus and Bifidobacterium (35% and 20% average abundance). Structural and functional diversity was significantly increased by week 30 but there was no further significant increase. At 42 weeks of age the most abundant genera were Bacteroides (16%), Prevotella (14%) and Megasphaera (8%). Significant differences in functional potential included an enrichment for genes in energy metabolism (carbon metabolism and oxidative phosphorylation) and depletion in cell motility (flagella and chemotaxis). We conclude that the feline faecal microbiome is predominantly determined by age when diet and environment are controlled for. We suggest this finding may also be informative for studies of the human microbiome, where control over such factors is usually limited.}, }
@article {pmid26655498, year = {2016}, author = {Kuleshov, V and Jiang, C and Zhou, W and Jahanbani, F and Batzoglou, S and Snyder, M}, title = {Synthetic long-read sequencing reveals intraspecies diversity in the human microbiome.}, journal = {Nature biotechnology}, volume = {34}, number = {1}, pages = {64-69}, pmid = {26655498}, issn = {1546-1696}, support = {P50 HG007735/HG/NHGRI NIH HHS/United States ; T32 HG000044/HG/NHGRI NIH HHS/United States ; U54 DK102556/DK/NIDDK NIH HHS/United States ; }, mesh = {*High-Throughput Nucleotide Sequencing ; Humans ; *Microbiota ; *Species Specificity ; }, abstract = {Identifying bacterial strains in metagenome and microbiome samples using computational analyses of short-read sequences remains a difficult problem. Here, we present an analysis of a human gut microbiome using TruSeq synthetic long reads combined with computational tools for metagenomic long-read assembly, variant calling and haplotyping (Nanoscope and Lens). Our analysis identifies 178 bacterial species, of which 51 were not found using shotgun reads alone. We recover bacterial contigs that comprise multiple operons, including 22 contigs of >1 Mbp. Furthermore, we observe extensive intraspecies variation within microbial strains in the form of haplotypes that span up to hundreds of Kbp. Incorporation of synthetic long-read sequencing technology with standard short-read approaches enables more precise and comprehensive analyses of metagenomic samples.}, }
@article {pmid26643044, year = {2015}, author = {Kort, R and Westerik, N and Mariela Serrano, L and Douillard, FP and Gottstein, W and Mukisa, IM and Tuijn, CJ and Basten, L and Hafkamp, B and Meijer, WC and Teusink, B and de Vos, WM and Reid, G and Sybesma, W}, title = {A novel consortium of Lactobacillus rhamnosus and Streptococcus thermophilus for increased access to functional fermented foods.}, journal = {Microbial cell factories}, volume = {14}, number = {}, pages = {195}, pmid = {26643044}, issn = {1475-2859}, mesh = {Africa, Eastern ; Animals ; Batch Cell Culture Techniques ; Functional Food/economics/*microbiology ; Genome, Bacterial ; Humans ; Lacticaseibacillus rhamnosus/genetics/*growth &amp; development/metabolism ; Milk/chemistry/microbiology ; Probiotics ; Streptococcus thermophilus/genetics/*growth &amp; development/metabolism ; }, abstract = {BACKGROUND: The lactic acid bacterium Lactobacillus rhamnosus GG is the most studied probiotic bacterium with proven health benefits upon oral intake, including the alleviation of diarrhea. The mission of the Yoba for Life foundation is to provide impoverished communities in Africa increased access to Lactobacillus rhamnosus GG under the name Lactobacillus rhamnosus yoba 2012, world's first generic probiotic strain. We have been able to overcome the strain's limitations to grow in food matrices like milk, by formulating a dried starter consortium with Streptococcus thermophilus that enables the propagation of both strains in milk and other food matrices. The affordable seed culture is used by people in resource-poor communities.<br><br>RESULTS: We used S. thermophilus C106 as an adjuvant culture for the propagation of L. rhamnosus yoba 2012 in a variety of fermented foods up to concentrations, because of its endogenous proteolytic activity, ability to degrade lactose and other synergistic effects. Subsequently, L. rhamnosus could reach final titers of 1E+09&#xa0;CFU&#xa0;ml(-1), which is sufficient to comply with the recommended daily dose for probiotics. The specific metabolic interactions between the two strains were derived from the full genome sequences of L. rhamnosus GG and S. thermophilus C106. The piliation of the L. rhamnosus yoba 2012, required for epithelial adhesion and inflammatory signaling in the human host, was stable during growth in milk for two rounds of fermentation. Sachets prepared with the two strains, yoba 2012 and C106, retained viability for at least 2 years.<br><br>CONCLUSIONS: A stable dried seed culture has been developed which facilitates local and low-cost production of a wide range of fermented foods that subsequently act as delivery vehicles for beneficial bacteria to communities in east Africa.}, }
@article {pmid26642878, year = {2015}, author = {Weinmaier, T and Probst, AJ and La Duc, MT and Ciobanu, D and Cheng, JF and Ivanova, N and Rattei, T and Vaishampayan, P}, title = {A viability-linked metagenomic analysis of cleanroom environments: eukarya, prokaryotes, and viruses.}, journal = {Microbiome}, volume = {3}, number = {}, pages = {62}, pmid = {26642878}, issn = {2049-2618}, mesh = {*Environment, Controlled ; *Environmental Microbiology ; Eukaryota/classification/genetics ; Humans ; *Metagenome ; *Metagenomics/methods ; Microbial Viability/*genetics ; Microbiota ; Prokaryotic Cells/classification ; RNA, Ribosomal, 16S/genetics ; Viruses/classification/genetics ; }, abstract = {BACKGROUND: Recent studies posit a reciprocal dependency between the microbiomes associated with humans and indoor environments. However, none of these metagenome surveys has considered the viability of constituent microorganisms when inferring impact on human health.<br><br>RESULTS: Reported here are the results of a viability-linked metagenomics assay, which (1) unveil a remarkably complex community profile for bacteria, fungi, and viruses and (2) bolster the detection of underrepresented taxa by eliminating biases resulting from extraneous DNA. This approach enabled, for the first time ever, the elucidation of viral genomes from a cleanroom environment. Upon comparing the viable biomes and distribution of phylotypes within a cleanroom and adjoining (uncontrolled) gowning enclosure, the rigorous cleaning and stringent control countermeasures of the former were observed to select for a greater presence of anaerobes and spore-forming microflora. Sequence abundance and correlation analyses suggest that the viable indoor microbiome is influenced by both the human microbiome and the surrounding ecosystem(s).<br><br>CONCLUSIONS: The findings of this investigation constitute the literature's first ever account of the indoor metagenome derived from DNA originating solely from the potential viable microbial population. Results presented in this study should prove valuable to the conceptualization and experimental design of future studies on indoor microbiomes aimed at inferring impact on human health.}, }
@article {pmid26610179, year = {2016}, author = {Hoisington, A and Maestre, JP and Kinney, KA and Siegel, JA}, title = {Characterizing the bacterial communities in retail stores in the United States.}, journal = {Indoor air}, volume = {26}, number = {6}, pages = {857-868}, doi = {10.1111/ina.12273}, pmid = {26610179}, issn = {1600-0668}, mesh = {*Air Microbiology ; Air Pollutants/*analysis ; Air Pollution, Indoor/*analysis ; Bacteria/*classification/genetics/*isolation &amp; purification ; *Commerce ; DNA, Bacterial/genetics ; Environmental Monitoring ; Humans ; Microbiota/*genetics ; United States ; Ventilation ; }, abstract = {The microorganisms present in retail environments have not been studied in detail despite the fact that these environments represent a potentially important location for exposure. In this study, HVAC filter dust samples in 13 US retail stores were collected and analyzed via pyrosequencing to characterize the indoor bacterial communities and to explore potential relationships between these communities and building and environmental parameters. Although retail stores contained a diverse bacterial community of 788 unique genera, over half of the nearly 118K sequences were attributed to the Proteobacteria phylum. Streptophyta, Bacillus, Corynebacterium, Pseudomonas, and Acinetobacter were the most prevalent genera detected. The recovered indoor airborne microbial community was statistically associated with both human oral and skin microbiota, indicating occupants are important contributors, despite a relatively low occupant density per unit volume in retail stores. Bacteria generally associated with outdoor environments were present in the indoor communities with no obvious association with air exchange rate, even when considering relative abundance. No significant association was observed between the indoor bacterial community recovered and store location, store type, or season. However, predictive functional gene profiling showed significant associations between the indoor community and season. The microbiome recovered from multiple samples collected months apart from the same building varied significantly indicating that caution is warranted when trying to characterize the bacterial community with a single sampling event.}, }
@article {pmid26602982, year = {2015}, author = {Mor, A and Driggers, PH and Segars, JH}, title = {Molecular characterization of the human microbiome from a reproductive perspective.}, journal = {Fertility and sterility}, volume = {104}, number = {6}, pages = {1344-1350}, doi = {10.1016/j.fertnstert.2015.10.008}, pmid = {26602982}, issn = {1556-5653}, mesh = {Bacteria/classification/*genetics/growth &amp; development/isolation &amp; purification ; Computational Biology ; DNA, Bacterial/*genetics/isolation &amp; purification ; Dysbiosis ; Female ; Genitalia/*microbiology/physiopathology ; Host-Pathogen Interactions ; Humans ; Infertility/microbiology/physiopathology ; Male ; *Microbiota ; *Molecular Diagnostic Techniques ; *Reproduction ; *Ribotyping ; }, abstract = {The process of reproduction inherently poses unique microbial challenges because it requires the transfer of gametes from one individual to the other, meanwhile preserving the integrity of the gametes and individuals from harmful microbes during the process. Advances in molecular biology techniques have expanded our understanding of the natural organisms living on and in our bodies, including those inhabiting the reproductive tract. Over the past two decades accumulating evidence has shown that the human microbiome is tightly related to health and disease states involving the different body systems, including the reproductive system. Here we introduce the science involved in the study of the human microbiome. We examine common methods currently used to characterize the human microbiome as an inseparable part of the reproductive system. Finally, we consider a few limitations, clinical implications, and the critical need for additional research in the field of human fertility.}, }
@article {pmid26601194, year = {2015}, author = {Liu, CM and Price, LB and Hungate, BA and Abraham, AG and Larsen, LA and Christensen, K and Stegger, M and Skov, R and Andersen, PS}, title = {Staphylococcus aureus and the ecology of the nasal microbiome.}, journal = {Science advances}, volume = {1}, number = {5}, pages = {e1400216}, pmid = {26601194}, issn = {2375-2548}, support = {R01 AI101371/AI/NIAID NIH HHS/United States ; R15 DE021194/DE/NIDCR NIH HHS/United States ; }, abstract = {The human microbiome can play a key role in host susceptibility to pathogens, including in the nasal cavity, a site favored by Staphylococcus aureus. However, what determines our resident nasal microbiota-the host or the environment-and can interactions among nasal bacteria determine S. aureus colonization? Our study of 46 monozygotic and 43 dizygotic twin pairs revealed that nasal microbiota is an environmentally derived trait, but the host's sex and genetics significantly influence nasal bacterial density. Although specific taxa, including lactic acid bacteria, can determine S. aureus colonization, their negative interactions depend on thresholds of absolute abundance. These findings demonstrate that nasal microbiota is not fixed by host genetics and opens the possibility that nasal microbiota may be manipulated to prevent or eliminate S. aureus colonization.}, }
@article {pmid26597628, year = {2015}, author = {Franasiak, JM and Scott, RT}, title = {Reproductive tract microbiome in assisted reproductive technologies.}, journal = {Fertility and sterility}, volume = {104}, number = {6}, pages = {1364-1371}, doi = {10.1016/j.fertnstert.2015.10.012}, pmid = {26597628}, issn = {1556-5653}, mesh = {Anti-Infective Agents/therapeutic use ; Bacteria/classification/drug effects/*growth &amp; development ; Female ; Fertility ; Genitalia/*microbiology/physiopathology ; Host-Pathogen Interactions ; Humans ; Infertility/microbiology/physiopathology/*therapy ; Male ; *Microbiota ; *Reproduction ; *Reproductive Techniques, Assisted ; Ribotyping ; Risk Factors ; Treatment Outcome ; }, abstract = {The human microbiome has gained much attention recently for its role in health and disease. This interest has come as we have begun to scratch the surface of the complexity of what has been deemed to be our "second genome" through initiatives such as the Human Microbiome Project. Microbes have been hypothesized to be involved in the physiology and pathophysiology of assisted reproduction since before the first success in IVF. Although the data supporting or refuting this hypothesis remain somewhat sparse, thanks to sequencing data from the 16S rRNA subunit, we have begun to characterize the microbiome in the male and female reproductive tracts and understand how this may play a role in reproductive competence. In this review, we discuss what is known about the microbiome of the reproductive tract as it pertains to assisted reproductive technologies.}, }
@article {pmid26589591, year = {2015}, author = {Levy, M and Thaiss, CA and Elinav, E}, title = {Metagenomic cross-talk: the regulatory interplay between immunogenomics and the microbiome.}, journal = {Genome medicine}, volume = {7}, number = {}, pages = {120}, pmid = {26589591}, issn = {1756-994X}, mesh = {Animals ; Gastrointestinal Tract/immunology/microbiology ; Gene Expression Regulation/immunology ; Genome, Microbial/genetics/immunology ; Humans ; Immune System/microbiology ; Immune System Diseases/immunology/microbiology ; Metagenomics/*methods ; Microbiota/*genetics/*immunology ; }, abstract = {The human microbiome, often referred to as the 'second genome', encompasses up to 100-fold more genes than the host genome. In contrast to the human genome, the microbial genome is flexible and amenable to change during the host's lifetime. As the composition of the microbial metagenome has been associated with the development of human disease, the mechanisms controlling the composition and function of the metagenome are of considerable interest and therapeutic potential. In the past few years, studies have revealed how the host immune system is involved in determining the microbial metagenome, and, in turn, how the microbiota regulates gene expression in the immune system. This species-specific bidirectional interaction is required for homeostatic health, whereas aberrations in the tightly controlled regulatory circuits that link the host immunogenome and the microbial metagenome drive susceptibility to common human diseases. Here, we summarize some of the major principles orchestrating this cross-talk between microbial and host genomes, with a special focus on the interaction between the intestinal immune system and the gut microbiome. Understanding the reciprocal genetic and epigenetic control between host and microbiota will be an important step towards the development of novel therapies against microbiome-driven diseases.}, }
@article {pmid26579434, year = {2015}, author = {Ridlon, JM and Bajaj, JS}, title = {The human gut sterolbiome: bile acid-microbiome endocrine aspects and therapeutics.}, journal = {Acta pharmaceutica Sinica. B}, volume = {5}, number = {2}, pages = {99-105}, pmid = {26579434}, issn = {2211-3835}, support = {R01 DK087913/DK/NIDDK NIH HHS/United States ; }, abstract = {The human body is now viewed as a complex ecosystem that on a cellular and gene level is mainly prokaryotic. The mammalian liver synthesizes and secretes hydrophilic primary bile acids, some of which enter the colon during the enterohepatic circulation, and are converted into numerous hydrophobic metabolites which are capable of entering the portal circulation, returned to the liver, and in humans, accumulating in the biliary pool. Bile acids are hormones that regulate their own synthesis, transport, in addition to glucose and lipid homeostasis, and energy balance. The gut microbial community through their capacity to produce bile acid metabolites distinct from the liver can be thought of as an "endocrine organ" with potential to alter host physiology, perhaps to their own favor. We propose the term "sterolbiome" to describe the genetic potential of the gut microbiome to produce endocrine molecules from endogenous and exogenous steroids in the mammalian gut. The affinity of secondary bile acid metabolites to host nuclear receptors is described, the potential of secondary bile acids to promote tumors, and the potential of bile acids to serve as therapeutic agents are discussed.}, }
@article {pmid26578596, year = {2016}, author = {Forster, SC and Browne, HP and Kumar, N and Hunt, M and Denise, H and Mitchell, A and Finn, RD and Lawley, TD}, title = {HPMCD: the database of human microbial communities from metagenomic datasets and microbial reference genomes.}, journal = {Nucleic acids research}, volume = {44}, number = {D1}, pages = {D604-9}, pmid = {26578596}, issn = {1362-4962}, support = {/WT_/Wellcome Trust/United Kingdom ; 1091097/MRC_/Medical Research Council/United Kingdom ; BB/M011755/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; 098051/WT_/Wellcome Trust/United Kingdom ; }, mesh = {*Databases, Nucleic Acid ; Disease ; Gastrointestinal Tract/microbiology/virology ; Genes, Microbial ; *Genome, Microbial ; Humans ; Internet ; *Metagenomics/standards ; Microbiota ; Molecular Sequence Annotation ; Reference Standards ; Sequence Analysis, DNA ; }, abstract = {The Human Pan-Microbe Communities (HPMC) database (http://www.hpmcd.org/) provides a manually curated, searchable, metagenomic resource to facilitate investigation of human gastrointestinal microbiota. Over the past decade, the application of metagenome sequencing to elucidate the microbial composition and functional capacity present in the human microbiome has revolutionized many concepts in our basic biology. When sufficient high quality reference genomes are available, whole genome metagenomic sequencing can provide direct biological insights and high-resolution classification. The HPMC database provides species level, standardized phylogenetic classification of over 1800 human gastrointestinal metagenomic samples. This is achieved by combining a manually curated list of bacterial genomes from human faecal samples with over 21000 additional reference genomes representing bacteria, viruses, archaea and fungi with manually curated species classification and enhanced sample metadata annotation. A user-friendly, web-based interface provides the ability to search for (i) microbial groups associated with health or disease state, (ii) health or disease states and community structure associated with a microbial group, (iii) the enrichment of a microbial gene or sequence and (iv) enrichment of a functional annotation. The HPMC database enables detailed analysis of human microbial communities and supports research from basic microbiology and immunology to therapeutic development in human health and disease.}, }
@article {pmid26576770, year = {2015}, author = {Fernandez, M and Riveros, JD and Campos, M and Mathee, K and Narasimhan, G}, title = {Microbial "social networks".}, journal = {BMC genomics}, volume = {16 Suppl 11}, number = {Suppl 11}, pages = {S6}, pmid = {26576770}, issn = {1471-2164}, mesh = {Bacteria/classification/*genetics ; *Bacterial Physiological Phenomena ; Female ; Humans ; Male ; Metagenomics/*methods ; Microbiota ; Middle Aged ; Smoking ; }, abstract = {BACKGROUND: It is well understood that distinct communities of bacteria are present at different sites of the body, and that changes in the structure of these communities have strong implications for human health. Yet, challenges remain in understanding the complex interconnections between the bacterial taxa within these microbial communities and how they change during the progression of diseases. Many recent studies attempt to analyze the human microbiome using traditional ecological measures and cataloging differences in bacterial community membership. In this paper, we show how to push metagenomic analyses beyond mundane questions related to the bacterial taxonomic profiles that differentiate one sample from another.<br><br>METHODS: We develop tools and techniques that help us to investigate the nature of social interactions in microbial communities, and demonstrate ways of compactly capturing extensive information about these networks and visually conveying them in an effective manner. We define the concept of bacterial "social clubs", which are groups of taxa that tend to appear together in many samples. More importantly, we define the concept of "rival clubs", entire groups that tend to avoid occurring together in many samples. We show how to efficiently compute social clubs and rival clubs and demonstrate their utility with the help of examples including a smokers' dataset and a dataset from the Human Microbiome Project (HMP).<br><br>RESULTS: The tools developed provide a framework for analyzing relationships between bacterial taxa modeled as bacterial co-occurrence networks. The computational techniques also provide a framework for identifying clubs and rival clubs and for studying differences in the microbiomes (and their interactions) of two or more collections of samples.<br><br>CONCLUSIONS: Microbial relationships are similar to those found in social networks. In this work, we assume that strong (positive or negative) tendencies to co-occur or co-infect is likely to have biological, physiological, or ecological significance, possibly as a result of cooperation or competition. As a consequence of the analysis, a variety of biological interpretations are conjectured. In the human microbiome context, the pattern of strength of interactions between bacterial taxa is unique to body site.}, }
@article {pmid26568984, year = {2015}, author = {Thomas, RM and Jobin, C}, title = {The Microbiome and Cancer: Is the 'Oncobiome' Mirage Real?.}, journal = {Trends in cancer}, volume = {1}, number = {1}, pages = {24-35}, pmid = {26568984}, issn = {2405-8033}, support = {R01 DK047700/DK/NIDDK NIH HHS/United States ; R01 DK073338/DK/NIDDK NIH HHS/United States ; }, abstract = {Investigations focused on the interplay between the human microbiome and cancer development, herein termed the 'oncobiome', have been growing at a rapid rate. However, these studies to date have primarily demonstrated associative relationships rather than causative ones. We pose the question of whether this emerging field of research is a 'mirage' without a clear picture, or truly represents a paradigm shift for cancer research. We propose the necessary steps needed to answer crucial questions and push the field forward to bring the mirage into a tangible reality.}, }
@article {pmid26568626, year = {2016}, author = {Biggs, MB and Papin, JA}, title = {Metabolic network-guided binning of metagenomic sequence fragments.}, journal = {Bioinformatics (Oxford, England)}, volume = {32}, number = {6}, pages = {867-874}, pmid = {26568626}, issn = {1367-4811}, support = {R01 GM108501/GM/NIGMS NIH HHS/United States ; T32 GM008715/GM/NIGMS NIH HHS/United States ; }, mesh = {Algorithms ; Cluster Analysis ; Humans ; Metabolic Networks and Pathways ; *Metagenomics ; Microbiota ; }, abstract = {MOTIVATION: Most microbes on Earth have never been grown in a laboratory, and can only be studied through DNA sequences. Environmental DNA sequence samples are complex mixtures of fragments from many different species, often unknown. There is a pressing need for methods that can reliably reconstruct genomes from complex metagenomic samples in order to address questions in ecology, bioremediation, and human health.<br><br>RESULTS: We present the SOrting by NEtwork Completion (SONEC) approach for assigning reactions to incomplete metabolic networks based on a metabolite connectivity score. We successfully demonstrate proof of concept in a set of 100 genome-scale metabolic network reconstructions, and delineate the variables that impact reaction assignment accuracy. We further demonstrate the integration of SONEC with existing approaches (such as cross-sample scaffold abundance profile clustering) on a set of 94 metagenomic samples from the Human Microbiome Project. We show that not only does SONEC aid in reconstructing species-level genomes, but it also improves functional predictions made with the resulting metabolic networks.<br><br>The datasets and code presented in this work are available at: https://bitbucket.org/mattbiggs/sorting_by_network_completion/<br><br>CONTACT: papin@virginia.edu<br><br>SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.}, }
@article {pmid26568112, year = {2015}, author = {Amato, KR and Yeoman, CJ and Cerda, G and Schmitt, CA and Cramer, JD and Miller, ME and Gomez, A and Turner, TR and Wilson, BA and Stumpf, RM and Nelson, KE and White, BA and Knight, R and Leigh, SR}, title = {Variable responses of human and non-human primate gut microbiomes to a Western diet.}, journal = {Microbiome}, volume = {3}, number = {}, pages = {53}, pmid = {26568112}, issn = {2049-2618}, support = {P40 OD010965/OD/NIH HHS/United States ; P40 RR019963/RR/NCRR NIH HHS/United States ; P51 OD011132/OD/NIH HHS/United States ; R01 RR016300/RR/NCRR NIH HHS/United States ; 5R01RR016300/RR/NCRR NIH HHS/United States ; }, mesh = {Animals ; Biological Evolution ; Carbohydrate Metabolism ; Chlorocebus aethiops ; *Diet, High-Fat ; *Diet, Western ; Dietary Proteins/*administration &amp; dosage ; Firmicutes/genetics/*isolation &amp; purification ; *Gastrointestinal Microbiome ; Humans ; Metagenomics/statistics &amp; numerical data ; *Microbiota ; Models, Animal ; Prevotella/genetics/*isolation &amp; purification ; }, abstract = {BACKGROUND: The human gut microbiota interacts closely with human diet and physiology. To better understand the mechanisms behind this relationship, gut microbiome research relies on complementing human studies with manipulations of animal models, including non-human primates. However, due to unique aspects of human diet and physiology, it is likely that host-gut microbe interactions operate differently in humans and non-human primates.<br><br>RESULTS: Here, we show that the human microbiome reacts differently to a high-protein, high-fat Western diet than that of a model primate, the African green monkey, or vervet (Chlorocebus aethiops sabaeus). Specifically, humans exhibit increased relative abundance of Firmicutes and reduced relative abundance of Prevotella on a Western diet while vervets show the opposite pattern. Predictive metagenomics demonstrate an increased relative abundance of genes associated with carbohydrate metabolism in the microbiome of only humans consuming a Western diet.<br><br>CONCLUSIONS: These results suggest that the human gut microbiota has unique properties that are a result of changes in human diet and physiology across evolution or that may have contributed to the evolution of human physiology. Therefore, the role of animal models for understanding the relationship between the human gut microbiota and host metabolism must be re-focused.}, }
@article {pmid26554691, year = {2015}, author = {Giusti, A}, title = {[Breastfeeding: health, prevention, and environment].}, journal = {Epidemiologia e prevenzione}, volume = {39}, number = {5-6}, pages = {386-391}, pmid = {26554691}, issn = {1120-9763}, mesh = {Adult ; Bottle Feeding/*statistics &amp; numerical data ; Breast Feeding/*statistics &amp; numerical data ; Evidence-Based Medicine ; Female ; Guidelines as Topic ; *Health Knowledge, Attitudes, Practice ; *Health Promotion ; Humans ; Infant ; Infant Formula/*statistics &amp; numerical data ; Infant, Newborn ; Italy/epidemiology ; Prevalence ; Risk Factors ; *Social Environment ; }, abstract = {Recently, a great deal of research in the field of neuroscience and human microbiome indicates the primal period (from preconceptional up to the early years of a child's life) as crucial to the future of the individual, opening new scenarios for the understanding of the processes underlying the human health. In recent decades, the social representation of infant feeding moved in fact from the normality of breastfeeding to the normal use of artificial formulas and bottle-feeding. Even the scientific thinking and the research production have been influenced by this phenomenon. In fact, a clear dominance of studies aimed to show the benefits of breast milk compared to formula milk rather than the risks of the latter compared to the biological norm of breastfeeding. Mother milk affects infant health also through his/her microbiome. Microbial colonisation startes during intrauterine life and continues through the vaginal canal at birth, during skin to skin contact immediately after birth, with colostrum and breastfeeding. The microbial exposure of infants delivered by the mother influences the development of the child microbiota, by programming his/her future health. However, rewriting the biological normality implies also a health professional paradigm shift such as departing from the systematic separation mother-child at birth, sticking at fixed schedules for breastfeeding time and duration, as it still happens in many birth centres. Breastfeeding has economic implications and the increase of its prevalence is associated with significant reduction of avoidable hospital admissions and medical care costs, both for the child and for the mother. Success in breastfeeding is the result of complex social interactions and not simply of an individual choice. However, any successful strategy must be oriented to the mother empowerment. Therefore, health professionals and community stakeholders have to learn and practice the health promotion approach, particularly avoiding prescribing appropriate breastfeeding behaviours to the mothers, but emphasizing her needs and preferences and her values system.}, }
@article {pmid26547201, year = {2016}, author = {Franasiak, JM and Werner, MD and Juneau, CR and Tao, X and Landis, J and Zhan, Y and Treff, NR and Scott, RT}, title = {Endometrial microbiome at the time of embryo transfer: next-generation sequencing of the 16S ribosomal subunit.}, journal = {Journal of assisted reproduction and genetics}, volume = {33}, number = {1}, pages = {129-136}, pmid = {26547201}, issn = {1573-7330}, mesh = {Adult ; Bacteria/classification/*genetics ; Embryo Transfer/methods ; Endometrium/growth &amp; development/*microbiology ; Female ; High-Throughput Nucleotide Sequencing ; Humans ; Metagenome/genetics ; Microbiota/*genetics ; Pregnancy ; Pregnancy Outcome ; RNA, Ribosomal, 16S/*genetics ; }, abstract = {PURPOSE: Characterization of the human microbiome has become more precise with the application of powerful molecular tools utilizing the unique 16S ribosomal subunit's hypervariable regions to greatly increase sensitivity. The microbiome of the lower genital tract can prognosticate obstetrical outcome while the upper reproductive tract remains poorly characterized. Here, the endometrial microbiome at the time of single embryo transfer (SET) is characterized by reproductive outcome.<br><br>METHODS: Consecutive patients undergoing euploid, SET was included in the analysis. After embryo transfer, performed as per routine, the most distal 5-mm portion of the transfer catheter was sterilely placed in a DNA free PCR tube. Next-generation sequencing of the bacteria specific 16S ribosome gene was performed, allowing genus and species calls for microorganisms.<br><br>RESULTS: Taxonomy assignments were made on 35 samples from 33 patients and 2 Escherichia coli controls. Of the 33 patients, 18 had ongoing pregnancies and 15 did not. There were a total of 278 different genus calls present across patient samples. The microbiome at time of transfer for those patients with ongoing pregnancy vs. those without ongoing pregnancy was characterized by top genera by sum fraction. Lactobacillus was the top species call for both outcomes.<br><br>CONCLUSIONS: The data presented here show the microbiome at the time of embryo transfer can successfully be characterized without altering standard clinical practice. This novel approach, both in specimen collection and analysis, is the first step toward the goal of determining physiologic from pathophysiologic microbiota. Further studies will help delineate if differences in the microbiome at the time of embryo transfer have a reliable impact on pregnancy outcome.}, }
@article {pmid26544875, year = {2015}, author = {Stone, VN and Parikh, HI and El-rami, F and Ge, X and Chen, W and Zhang, Y and Kellogg, GE and Xu, P}, title = {Identification of Small-Molecule Inhibitors against Meso-2, 6-Diaminopimelate Dehydrogenase from Porphyromonas gingivalis.}, journal = {PloS one}, volume = {10}, number = {11}, pages = {e0141126}, pmid = {26544875}, issn = {1932-6203}, support = {R01 DE023078/DE/NIDCR NIH HHS/United States ; F31DE024038/DE/NIDCR NIH HHS/United States ; R01DE018138/DE/NIDCR NIH HHS/United States ; R01DE023078/DE/NIDCR NIH HHS/United States ; F31 DE024038/DE/NIDCR NIH HHS/United States ; S10 RR022495/RR/NCRR NIH HHS/United States ; P30 CA016059/CA/NCI NIH HHS/United States ; P30 NS047463/NS/NINDS NIH HHS/United States ; R01 DE018138/DE/NIDCR NIH HHS/United States ; }, mesh = {Amino Acid Oxidoreductases/*antagonists &amp; inhibitors/genetics/metabolism ; Amino Acid Sequence ; Anti-Bacterial Agents/chemistry/*pharmacology ; Bacteroidaceae Infections/*drug therapy/enzymology/microbiology ; Cloning, Molecular ; Escherichia coli/drug effects/*enzymology ; High-Throughput Screening Assays/*methods ; Humans ; Models, Molecular ; Molecular Sequence Data ; NADP/metabolism ; Porphyromonas gingivalis/*drug effects/*enzymology ; Protein Conformation ; Sequence Homology, Amino Acid ; Small Molecule Libraries/chemistry/*pharmacology ; Substrate Specificity ; }, abstract = {Species-specific antimicrobial therapy has the potential to combat the increasing threat of antibiotic resistance and alteration of the human microbiome. We therefore set out to demonstrate the beginning of a pathogen-selective drug discovery method using the periodontal pathogen Porphyromonas gingivalis as a model. Through our knowledge of metabolic networks and essential genes we identified a "druggable" essential target, meso-diaminopimelate dehydrogenase, which is found in a limited number of species. We adopted a high-throughput virtual screen method on the ZINC chemical library to select a group of potential small-molecule inhibitors. Meso-diaminopimelate dehydrogenase from P. gingivalis was first expressed and purified in Escherichia coli then characterized for enzymatic inhibitor screening studies. Several inhibitors with similar structural scaffolds containing a sulfonamide core and aromatic substituents showed dose-dependent inhibition. These compounds were further assayed showing reasonable whole-cell activity and the inhibition mechanism was determined. We conclude that the establishment of this target and screening strategy provides a model for the future development of new antimicrobials.}, }
@article {pmid26530830, year = {2015}, author = {McDonald, D and Birmingham, A and Knight, R}, title = {Context and the human microbiome.}, journal = {Microbiome}, volume = {3}, number = {}, pages = {52}, pmid = {26530830}, issn = {2049-2618}, mesh = {Databases, Factual ; Gastrointestinal Microbiome ; Humans ; *Microbiota ; Research ; }, abstract = {Human microbiome reference datasets provide epidemiological context for researchers, enabling them to uncover new insights into their own data through meta-analyses. In addition, large and comprehensive reference sets offer a means to develop or test hypotheses and can pave the way for addressing practical study design considerations such as sample size decisions. We discuss the importance of reference sets in human microbiome research, limitations of existing resources, technical challenges to employing reference sets, examples of their usage, and contributions of the American Gut Project to the development of a comprehensive reference set. Through engaging the general public, the American Gut Project aims to address many of the issues present in existing reference resources, characterizing health and disease, lifestyle, and dietary choices of the participants while extending its efforts globally through international collaborations.}, }
@article {pmid26525290, year = {2015}, author = {Babickova, J and Gardlik, R}, title = {Pathological and therapeutic interactions between bacteriophages, microbes and the host in inflammatory bowel disease.}, journal = {World journal of gastroenterology}, volume = {21}, number = {40}, pages = {11321-11330}, pmid = {26525290}, issn = {2219-2840}, mesh = {Anti-Bacterial Agents/therapeutic use ; Bacteria/drug effects/*virology ; *Bacteriophages ; Dysbiosis ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome/drug effects ; Host-Pathogen Interactions ; Humans ; Inflammatory Bowel Diseases/diagnosis/immunology/*microbiology/therapy ; Intestines/drug effects/immunology/*microbiology ; Probiotics/therapeutic use ; }, abstract = {The intestinal microbiome is a dynamic system of interactions between the host and its microbes. Under physiological conditions, a fine balance and mutually beneficial relationship is present. Disruption of this balance is a hallmark of inflammatory bowel disease (IBD). Whether an altered microbiome is the consequence or the cause of IBD is currently not fully understood. The pathogenesis of IBD is believed to be a complex interaction between genetic predisposition, the immune system and environmental factors. In the recent years, metagenomic studies of the human microbiome have provided useful data that are helping to assemble the IBD puzzle. In this review, we summarize and discuss current knowledge on the composition of the intestinal microbiota in IBD, host-microbe interactions and therapeutic possibilities using bacteria in IBD. Moreover, an outlook on the possible contribution of bacteriophages in the pathogenesis and therapy of IBD is provided.}, }
@article {pmid26523201, year = {2015}, author = {Lagier, JC and Khelaifia, S and Azhar, EI and Croce, O and Bibi, F and Jiman-Fatani, AA and Yasir, M and Helaby, HB and Robert, C and Fournier, PE and Raoult, D}, title = {Genome sequence of Oceanobacillus picturae strain S1, an halophilic bacterium first isolated in human gut.}, journal = {Standards in genomic sciences}, volume = {10}, number = {}, pages = {91}, pmid = {26523201}, issn = {1944-3277}, abstract = {Oceanobacillus picturae is a strain of a moderately halophilic bacterium, first isolated from a mural painting. We demonstrate, for the first time, the culture of human Oceanobacillus picturae, strain S1(T), whose genome is described here, from a stool sample collected from a 25-year-old Saoudian healthy individual. We used a slightly modified standard culture medium adding 100 g/L of NaCl. We provide a short description of this strain including its MALDI-TOF spectrum, the main identification tool currently used in clinical microbiology. The 3,675,175 bp long genome exhibits a G + C content of 39.15 % and contains 3666 protein-coding and 157 RNA genes. The draft genome sequence of Oceanobacillus picturae has a similar size to the Oceanobacillus kimchii (respectively 3.67 Mb versus 3.83 Mb). The G + C content was higher compared with Oceanobacillus kimchii (respectively 39.15 % and 35.2 %). Oceanobacillus picturae shared almost identical number of genes (3823 genes versus 3879 genes), with a similar ratio of genes per Mb (1041 genes/Mb versus 1012 genes/Mb). The genome sequencing of Oceanobacillus picturae strain S1 isolated for the first time in a human, will be added to the 778 genome projects from the gastrointestinal tract listed by the international consortium Human Microbiome Project.}, }
@article {pmid26515381, year = {2015}, author = {Franasiak, JM and Scott, RT}, title = {Introduction: Microbiome in human reproduction.}, journal = {Fertility and sterility}, volume = {104}, number = {6}, pages = {1341-1343}, doi = {10.1016/j.fertnstert.2015.10.021}, pmid = {26515381}, issn = {1556-5653}, mesh = {Bacteria/*growth &amp; development ; Biofilms ; Dysbiosis ; Female ; Fertility ; Genitalia/*microbiology/physiopathology ; Host-Pathogen Interactions ; Humans ; Infertility/*microbiology/physiopathology/therapy ; Male ; *Microbiota ; *Reproduction ; Reproductive Techniques, Assisted ; }, abstract = {The human microbiome has been termed the "second human genome" and data that has come about of late certainly makes it appear every bit as complex. The human body contains 10-fold more microbial cells than the human cells and accounts for 1%-3% of our total body mass. As we learn more about this symbiotic relationship, it appears this complex interaction occurs in nearly every part of the body, even those areas at one time considered to be sterile. Indeed, the microbiome in human reproduction has been investigated in terms of both the lower and upper reproductive tract and includes interactions even at the point of gametogenesis. What is all the more fascinating is that we have known about the importance of microbes for over 150 years, even before they existed in name. And now, with the assistance of an exciting technologic revolution which has pushed forward our understanding of the microbiome, we appear to stand on the precipice of a higher level of understanding of microbes, the biofilms they create, and their impact of health and disease in human reproduction.}, }
@article {pmid26512100, year = {2015}, author = {Jones, MB and Highlander, SK and Anderson, EL and Li, W and Dayrit, M and Klitgord, N and Fabani, MM and Seguritan, V and Green, J and Pride, DT and Yooseph, S and Biggs, W and Nelson, KE and Venter, JC}, title = {Library preparation methodology can influence genomic and functional predictions in human microbiome research.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {112}, number = {45}, pages = {14024-14029}, pmid = {26512100}, issn = {1091-6490}, mesh = {Analysis of Variance ; Base Composition ; Base Sequence ; Feces/chemistry ; *Gene Library ; Genome, Bacterial/*genetics ; High-Throughput Nucleotide Sequencing/*methods ; Humans ; Metagenomics/*methods/trends ; Microbiota/*genetics ; Molecular Sequence Data ; Polymerase Chain Reaction ; Sequence Analysis, DNA ; Species Specificity ; }, abstract = {Observations from human microbiome studies are often conflicting or inconclusive. Many factors likely contribute to these issues including small cohort sizes, sample collection, and handling and processing differences. The field of microbiome research is moving from 16S rDNA gene sequencing to a more comprehensive genomic and functional representation through whole-genome sequencing (WGS) of complete communities. Here we performed quantitative and qualitative analyses comparing WGS metagenomic data from human stool specimens using the Illumina Nextera XT and Illumina TruSeq DNA PCR-free kits, and the KAPA Biosystems Hyper Prep PCR and PCR-free systems. Significant differences in taxonomy are observed among the four different next-generation sequencing library preparations using a DNA mock community and a cell control of known concentration. We also revealed biases in error profiles, duplication rates, and loss of reads representing organisms that have a high %G+C content that can significantly impact results. As with all methods, the use of benchmarking controls has revealed critical differences among methods that impact sequencing results and later would impact study interpretation. We recommend that the community adopt PCR-free-based approaches to reduce PCR bias that affects calculations of abundance and to improve assemblies for accurate taxonomic assignment. Furthermore, the inclusion of a known-input cell spike-in control provides accurate quantitation of organisms in clinical samples.}, }
@article {pmid26509922, year = {2015}, author = {Challinor, VL and Bode, HB}, title = {Bioactive natural products from novel microbial sources.}, journal = {Annals of the New York Academy of Sciences}, volume = {1354}, number = {}, pages = {82-97}, doi = {10.1111/nyas.12954}, pmid = {26509922}, issn = {1749-6632}, mesh = {Animals ; Anti-Bacterial Agents/metabolism/*pharmacology ; Bacteria/classification/*drug effects/metabolism ; Bacterial Infections/microbiology ; Biological Products/metabolism/*pharmacology ; Drug Resistance, Microbial/*drug effects ; Humans ; Insecta/microbiology ; Nematoda/microbiology ; Symbiosis ; }, abstract = {Despite the importance of microbial natural products for human health, only a few bacterial genera have been mined for the new natural products needed to overcome the urgent threat of antibiotic resistance. This is surprising, given that genome sequencing projects have revealed that the capability to produce natural products is not a rare feature among bacteria. Even the bacteria occurring in the human microbiome produce potent antibiotics, and thus potentially are an untapped resource for novel compounds, potentially with new activities. This review highlights examples of bacteria that should be considered new sources of natural products, including anaerobes, pathogens, and symbionts of humans, insects, and nematodes. Exploitation of these producer strains, combined with advances in modern natural product research methodology, has the potential to open the way for a new golden age of microbial therapeutics.}, }
@article {pmid26500908, year = {2015}, author = {Kali, A}, title = {Human Microbiome Engineering: The Future and Beyond.}, journal = {Journal of clinical and diagnostic research : JCDR}, volume = {9}, number = {9}, pages = {DE01-4}, pmid = {26500908}, issn = {2249-782X}, abstract = {Microbial flora of skin and mucosal surface are vital component of human biology. Current research indicates that this microbial constellation, rather than being inert commensals, has greater implications in health and disease. They play essential role in metabolism, immunity, inflammation, neuro-endocrine regulation and even moderate host response to cancer. Genetic engineering was a major breakthrough in medical research in 1970's and it opened up newer dimensions in vaccinology, large-scale synthesis of bio-molecule and drug development. Engineering human microbiome is a novel concept. Recombinant DNA technology can be employed to modify the genome of critical components of resident microflora to achieve unprecedented goals.}, }
@article {pmid26500804, year = {2015}, author = {Davis, C and Kota, K and Baldhandapani, V and Gong, W and Abubucker, S and Becker, E and Martin, J and Wylie, KM and Khetani, R and Hudson, ME and Weinstock, GM and Mitreva, M}, title = {mBLAST: Keeping up with the sequencing explosion for (meta)genome analysis.}, journal = {Journal of data mining in genomics &amp; proteomics}, volume = {4}, number = {3}, pages = {}, pmid = {26500804}, issn = {2153-0602}, support = {U54 HG003079/HG/NHGRI NIH HHS/United States ; U54 HG004968/HG/NHGRI NIH HHS/United States ; }, abstract = {Recent advances in next-generation sequencing technologies require alignment algorithms and software that can keep pace with the heightened data production. Standard algorithms, especially protein similarity searches, represent significant bottlenecks in analysis pipelines. For metagenomic approaches in particular, it is now often necessary to search hundreds of millions of sequence reads against large databases. Here we describe mBLAST, an accelerated search algorithm for translated and/or protein alignments to large datasets based on the Basic Local Alignment Search Tool (BLAST) and retaining the high sensitivity of BLAST. The mBLAST algorithms achieve substantial speed up over the National Center for Biotechnology Information (NCBI) programs BLASTX, TBLASTX and BLASTP for large datasets, allowing analysis within reasonable timeframes on standard computer architectures. In this article, the impact of mBLAST is demonstrated with sequences originating from the microbiota of healthy humans from the Human Microbiome Project. mBLAST is designed as a plug-in replacement for BLAST for any study that involves short-read sequences and includes high-throughput analysis. The mBLAST software is freely available to academic users at www.multicorewareinc.com.}, }
@article {pmid26500616, year = {2015}, author = {Belizário, JE and Napolitano, M}, title = {Human microbiomes and their roles in dysbiosis, common diseases, and novel therapeutic approaches.}, journal = {Frontiers in microbiology}, volume = {6}, number = {}, pages = {1050}, pmid = {26500616}, issn = {1664-302X}, abstract = {The human body is the residence of a large number of commensal (non-pathogenic) and pathogenic microbial species that have co-evolved with the human genome, adaptive immune system, and diet. With recent advances in DNA-based technologies, we initiated the exploration of bacterial gene functions and their role in human health. The main goal of the human microbiome project is to characterize the abundance, diversity and functionality of the genes present in all microorganisms that permanently live in different sites of the human body. The gut microbiota expresses over 3.3 million bacterial genes, while the human genome expresses only 20 thousand genes. Microbe gene-products exert pivotal functions via the regulation of food digestion and immune system development. Studies are confirming that manipulation of non-pathogenic bacterial strains in the host can stimulate the recovery of the immune response to pathogenic bacteria causing diseases. Different approaches, including the use of nutraceutics (prebiotics and probiotics) as well as phages engineered with CRISPR/Cas systems and quorum sensing systems have been developed as new therapies for controlling dysbiosis (alterations in microbial community) and common diseases (e.g., diabetes and obesity). The designing and production of pharmaceuticals based on our own body's microbiome is an emerging field and is rapidly growing to be fully explored in the near future. This review provides an outlook on recent findings on the human microbiomes, their impact on health and diseases, and on the development of targeted therapies.}, }
@article {pmid26493119, year = {2015}, author = {Fox, C and Eichelberger, K}, title = {Maternal microbiome and pregnancy outcomes.}, journal = {Fertility and sterility}, volume = {104}, number = {6}, pages = {1358-1363}, doi = {10.1016/j.fertnstert.2015.09.037}, pmid = {26493119}, issn = {1556-5653}, mesh = {Bacteria/*growth &amp; development/pathogenicity ; Dysbiosis ; Female ; Gene-Environment Interaction ; Host-Pathogen Interactions ; Humans ; *Microbiota ; Placenta/*microbiology ; Pregnancy ; Pregnancy Complications, Infectious/genetics/*microbiology/physiopathology/prevention &amp; control ; *Pregnancy Outcome ; Risk Factors ; Vagina/*microbiology ; Virulence ; }, abstract = {Alterations of the human microbiome are a known characteristic of various inflammatory disease states and have been linked to spontaneous preterm birth and other adverse pregnancy outcomes. Recent advances in metagenomic research have proven that the placenta harbors its own rich diverse microbiome, even in clinically healthy pregnancies, and preterm birth may be a result of hematogenous infection rather than exclusively ascending infection as previously hypothesized. In this review, we describe the microbiome in healthy nongravid and gravid women to contrast it with the alterations of the microbiome associated with spontaneous preterm birth. We also discuss the importance of host gene-environment interactions and the potential for microbiota-specific targeted therapies to reduce the risk of adverse pregnancy outcomes.}, }
@article {pmid26477544, year = {2016}, author = {Younes, JA and Klappe, K and Kok, JW and Busscher, HJ and Reid, G and van der Mei, HC}, title = {Vaginal epithelial cells regulate membrane adhesiveness to co-ordinate bacterial adhesion.}, journal = {Cellular microbiology}, volume = {18}, number = {4}, pages = {605-614}, doi = {10.1111/cmi.12537}, pmid = {26477544}, issn = {1462-5822}, mesh = {Adhesiveness ; *Bacterial Adhesion ; Cell Line ; Cell Membrane/*physiology ; Epithelial Cells/*microbiology ; Female ; Humans ; Vagina/*microbiology ; }, abstract = {Vaginal epithelium is colonized by different bacterial strains and species. The bacterial composition of vaginal biofilms controls the balance between health and disease. Little is known about the relative contribution of the epithelial and bacterial cell surfaces to bacterial adhesion and whether and how adhesion is regulated over cell membrane regions. Here, we show that bacterial adhesion forces with cell membrane regions not located above the nucleus are stronger than with regions above the nucleus both for vaginal pathogens and different commensal and probiotic lactobacillus strains involved in health. Importantly, adhesion force ratios over membrane regions away from and above the nucleus coincided with the ratios between numbers of adhering bacteria over both regions. Bacterial adhesion forces were dramatically decreased by depleting the epithelial cell membrane of cholesterol or sub-membrane cortical actin. Thus, epithelial cells can regulate membrane regions to which bacterial adhesion is discouraged, possibly to protect the nucleus.}, }
@article {pmid26466817, year = {2016}, author = {Arjunan, P and El-Awady, A and Dannebaum, RO and Kunde-Ramamoorthy, G and Cutler, CW}, title = {High-throughput sequencing reveals key genes and immune homeostatic pathways activated in myeloid dendritic cells by Porphyromonas gingivalis 381 and its fimbrial mutants.}, journal = {Molecular oral microbiology}, volume = {31}, number = {1}, pages = {78-93}, pmid = {26466817}, issn = {2041-1014}, support = {F31 DE020014/DE/NIDCR NIH HHS/United States ; R01 DE014328/DE/NIDCR NIH HHS/United States ; R21 DE020916/DE/NIDCR NIH HHS/United States ; R01 DE14328-09/DE/NIDCR NIH HHS/United States ; }, mesh = {Adhesins, Bacterial/genetics/*immunology ; Bacterial Proteins/genetics/metabolism ; Dendritic Cells/*immunology/*microbiology ; Fimbriae Proteins/genetics/metabolism ; Fimbriae, Bacterial/genetics/*immunology ; Gene Expression ; High-Throughput Nucleotide Sequencing/methods ; Humans ; Immunity, Cellular ; Microbiota/genetics/immunology ; Monocytes/immunology ; Mutation ; Myeloid Cells/drug effects/*immunology/*microbiology ; Periodontitis/immunology/microbiology ; Porphyromonas gingivalis/*immunology ; Sequence Analysis, RNA ; Transcriptome ; }, abstract = {The human microbiome consists of highly diverse microbial communities that colonize our skin and mucosal surfaces, aiding in maintenance of immune homeostasis. The keystone pathogen Porphyromonas gingivalis induces a dysbiosis and disrupts immune homeostasis through as yet unclear mechanisms. The fimbrial adhesins of P. gingivalis facilitate biofilm formation, invasion of and dissemination by blood dendritic cells; hence, fimbriae may be key factors in disruption of immune homeostasis. In this study we employed RNA-sequencing transcriptome profiling to identify differentially expressed genes (DEGs) in human monocyte-derived dendritic cells (MoDCs) in response to in vitro infection/exposure by Pg381 or its isogenic mutant strains that solely express minor-Mfa1 fimbriae (DPG3), major-FimA fimbriae (MFI) or are deficient in both fimbriae (MFB) relative to uninfected control. Our results yielded a total of 479 DEGs that were at least two-fold upregulated and downregulated in MoDCs significantly (P ≤ 0.05) by all four strains and certain DEGs that were strain-specific. Interestingly, the gene ontology biological and functional analysis shows that the upregulated genes in DPG3-induced MoDCs were more significant than other strains and associated with inflammation, immune response, anti-apoptosis, cell proliferation, and other homeostatic functions. Both transcriptome and quantitative polymerase chain reaction results show that DPG3, which solely expresses Mfa1, increased ZNF366, CD209, LOX1, IDO1, IL-10, CCL2, SOCS3, STAT3 and FOXO1 gene expression. In conclusion, we have identified key DC-mediated immune homeostatic pathways that could contribute to dysbiosis in periodontal infection with P. gingivalis.}, }
@article {pmid26462363, year = {2015}, author = {Vitetta, L and Palacios, T and Hall, S and Coulson, S}, title = {Gastrointestinal Tract Commensal Bacteria and Probiotics: Influence on End-Organ Physiology.}, journal = {Progress in drug research. Fortschritte der Arzneimittelforschung. Progres des recherches pharmaceutiques}, volume = {70}, number = {}, pages = {1-33}, doi = {10.1007/978-3-0348-0927-6_1}, pmid = {26462363}, issn = {0071-786X}, mesh = {Animals ; Bacteria/*isolation &amp; purification ; Gastrointestinal Tract/*microbiology ; Humans ; Hygiene ; Immune Tolerance ; Microbiota ; Probiotics/*therapeutic use ; }, abstract = {Bacteria represent the earliest form of independent life on this planet. Bacterial development has included cooperative symbiosis with plants (e.g., Leguminosae family and nitrogen fixing bacteria in soil) and animals (e.g., the gut microbiome). It is generally agreed upon that the fusion of two prokaryotes evolutionarily gave rise to the eukaryotic cell in which mitochondria may be envisaged as a genetically functional mosaic, a relic from one of the prokaryotes. This is expressed by the appearance of mitochondria in eukaryotic cells (an alpha-proteobacteria input), a significant endosymbiotic evolutionary event. As such, the evolution of human life has been complexly connected to bacterial activities. Hence, microbial colonization of mammals has been a progressively driven process. The interactions between the human host and the microbiome inhabiting the gastrointestinal tract (GIT) for example, afford the human host the necessary cues for the development of regulated signals that in part are induced by reactive oxygen species (ROS). This regulated activity then promotes immunological tolerance and metabolic regulation and stability, which then helps establish control of local and extraintestinal end-organ (e.g., kidneys) physiology. Pharmacobiotics, the targeted administration of live probiotic cultures, is an advancing area of potential therapeutics, either directly or as adjuvants. Hence the continued scientific understanding of the human microbiome in health and disease may further lead to fine tuning the targeted delivery of probiotics for a therapeutic gain.}, }
@article {pmid26456470, year = {2016}, author = {Trautman, EP and Crawford, JM}, title = {Linking Biosynthetic Gene Clusters to their Metabolites via Pathway- Targeted Molecular Networking.}, journal = {Current topics in medicinal chemistry}, volume = {16}, number = {15}, pages = {1705-1716}, pmid = {26456470}, issn = {1873-4294}, support = {DP2 CA186575/CA/NCI NIH HHS/United States ; R00 GM097096/GM/NIGMS NIH HHS/United States ; 1DP2-CA186575/CA/NCI NIH HHS/United States ; R00-GM097096/GM/NIGMS NIH HHS/United States ; }, mesh = {Biological Products/*metabolism ; Biosynthetic Pathways/*genetics ; Computational Biology ; Humans ; Metabolic Networks and Pathways/*genetics ; Microbiota/genetics ; *Multigene Family ; }, abstract = {The connection of microbial biosynthetic gene clusters to the small molecule metabolites they encode is central to the discovery and characterization of new metabolic pathways with ecological and pharmacological potential. With increasing microbial genome sequence information being deposited into publicly available databases, it is clear that microbes have the coding capacity for many more biologically active small molecules than previously realized. Of increasing interest are the small molecules encoded by the human microbiome, as these metabolites likely mediate a variety of currently uncharacterized human-microbe interactions that influence health and disease. In this mini-review, we describe the ongoing biosynthetic, structural, and functional characterizations of the genotoxic colibactin pathway in gut bacteria as a thematic example of linking biosynthetic gene clusters to their metabolites. We also highlight other natural products that are produced through analogous biosynthetic logic and comment on some current disconnects between bioinformatics predictions and experimental structural characterizations. Lastly, we describe the use of pathway-targeted molecular networking as a tool to characterize secondary metabolic pathways within complex metabolomes and to aid in downstream metabolite structural elucidation efforts.}, }
@article {pmid26442272, year = {2015}, author = {Allison, DB and Bassaganya-Riera, J and Burlingame, B and Brown, AW and le Coutre, J and Dickson, SL and van Eden, W and Garssen, J and Hontecillas, R and Khoo, CS and Knorr, D and Kussmann, M and Magistretti, PJ and Mehta, T and Meule, A and Rychlik, M and Vögele, C}, title = {Goals in Nutrition Science 2015-2020.}, journal = {Frontiers in nutrition}, volume = {2}, number = {}, pages = {26}, pmid = {26442272}, issn = {2296-861X}, }
@article {pmid26437943, year = {2015}, author = {Ning, J and Beiko, RG}, title = {Phylogenetic approaches to microbial community classification.}, journal = {Microbiome}, volume = {3}, number = {}, pages = {47}, pmid = {26437943}, issn = {2049-2618}, mesh = {Biodiversity ; Dental Plaque/microbiology ; Humans ; *Metagenome ; *Microbiota ; Mouth/microbiology ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Supervised Machine Learning ; }, abstract = {BACKGROUND: The microbiota from different body sites are dominated by different major groups of microbes, but the variations within a body site such as the mouth can be more subtle. Accurate predictive models can serve as useful tools for distinguishing sub-sites and understanding key organisms and their roles and can highlight deviations from expected distributions of microbes. Good classification depends on choosing the right combination of classifier, feature representation, and learning model. Machine-learning procedures have been used in the past for supervised classification, but increased attention to feature representation and selection may produce better models and predictions.<br><br>RESULTS: We focused our attention on the classification of nine oral sites and dental plaque in particular, using data collected from the Human Microbiome Project. A key focus of our representations was the use of phylogenetic information, both as the basis for custom kernels and as a way to represent sets of microbes to the classifier. We also used the PICRUSt software, which draws on phylogenetic relationships to predict molecular functions and to generate additional features for the classifier. Custom kernels based on the UniFrac measure of community dissimilarity did not improve performance. However, feature representation was vital to classification accuracy, with microbial clade and function representations providing useful information to the classifier; combining the two types of features did not yield increased prediction accuracy. Many of the best-performing clades and functions had clear associations with oral microflora.<br><br>CONCLUSIONS: The classification of oral microbiota remains a challenging problem; our best accuracy on the plaque dataset was approximately 81&#xa0;%. Perfect accuracy may be unattainable due to the close proximity of the sites and intra-individual variation. However, further exploration of the space of both classifiers and feature representations is likely to increase the accuracy of predictive models.}, }
@article {pmid26431583, year = {2016}, author = {Song, H and Yoo, Y and Hwang, J and Na, YC and Kim, HS}, title = {Faecalibacterium prausnitzii subspecies-level dysbiosis in the human gut microbiome underlying atopic dermatitis.}, journal = {The Journal of allergy and clinical immunology}, volume = {137}, number = {3}, pages = {852-860}, doi = {10.1016/j.jaci.2015.08.021}, pmid = {26431583}, issn = {1097-6825}, mesh = {*Clostridiales/classification/genetics/metabolism ; Cluster Analysis ; Computational Biology/methods ; Dermatitis, Atopic/*etiology ; *Dysbiosis ; Feces/microbiology ; Female ; *Gastrointestinal Microbiome ; Humans ; Male ; Metagenome ; Metagenomics ; Models, Biological ; Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; }, abstract = {BACKGROUND: Atopic dermatitis (AD) is a serious global epidemic associated with a modern lifestyle.<br><br>OBJECTIVE: Although aberrant interactions between gut microbes and the intestinal immune system have been implicated in this skin disease, the nature of the microbiome dysfunction underlying the disease remains unclear.<br><br>METHODS: The gut microbiome from 132 subjects, including 90 patients with AD, was analyzed by using 16S rRNA gene and metagenome sequence analyses. Reference genomes from the Human Microbiome Project and the KEGG Orthology database were used for metagenome analyses. Short-chain fatty acids in fecal samples were compared by using gas chromatographic-mass spectrometric analyses.<br><br>RESULTS: We show that enrichment of a subspecies of the major gut species Faecalibacterium prausnitzii is strongly associated with AD. In addition, the AD microbiome was enriched in genes encoding the use of various nutrients that could be released from damaged gut epithelium, reflecting a bloom of auxotrophic bacteria. Fecal samples from patients with AD showed decreased levels of butyrate and propionate, which have anti-inflammatory effects. This is likely a consequence of an intraspecies compositional change in F prausnitzii that reduces the number of high butyrate and propionate producers, including those related to the strain A2-165, a lack of which has been implicated in patients with Crohn disease.<br><br>CONCLUSIONS: The data suggest that feedback interactions between dysbiosis in F prausnitzii and dysregulation of gut epithelial inflammation might underlie the chronic progression of AD by resulting in impairment of the gut epithelial barrier, which ultimately leads to aberrant TH2-type immune responses to allergens in the skin.}, }
@article {pmid26421278, year = {2015}, author = {Cao, Y and Zheng, X and Li, F and Bo, X}, title = {mmnet: An R Package for Metagenomics Systems Biology Analysis.}, journal = {BioMed research international}, volume = {2015}, number = {}, pages = {167249}, pmid = {26421278}, issn = {2314-6141}, mesh = {Humans ; *Metabolic Networks and Pathways/genetics ; *Metagenomics ; *Software ; *Systems Biology ; }, abstract = {The human microbiome plays important roles in human health and disease. Previous microbiome studies focused mainly on single pure species function and overlooked the interactions in the complex communities on system-level. A metagenomic approach introduced recently integrates metagenomic data with community-level metabolic network modeling, but no comprehensive tool was available for such kind of approaches. To facilitate these kinds of studies, we developed an R package, mmnet, to implement community-level metabolic network reconstruction. The package also implements a set of functions for automatic analysis pipeline construction including functional annotation of metagenomic reads, abundance estimation of enzymatic genes, community-level metabolic network reconstruction, and integrated network analysis. The result can be represented in an intuitive way and sent to Cytoscape for further exploration. The package has substantial potentials in metagenomic studies that focus on identifying system-level variations of human microbiome associated with disease.}, }
@article {pmid26417541, year = {2015}, author = {Meadow, JF and Altrichter, AE and Bateman, AC and Stenson, J and Brown, GZ and Green, JL and Bohannan, BJ}, title = {Humans differ in their personal microbial cloud.}, journal = {PeerJ}, volume = {3}, number = {}, pages = {e1258}, pmid = {26417541}, issn = {2167-8359}, abstract = {Dispersal of microbes between humans and the built environment can occur through direct contact with surfaces or through airborne release; the latter mechanism remains poorly understood. Humans emit upwards of 10(6) biological particles per hour, and have long been known to transmit pathogens to other individuals and to indoor surfaces. However it has not previously been demonstrated that humans emit a detectible microbial cloud into surrounding indoor air, nor whether such clouds are sufficiently differentiated to allow the identification of individual occupants. We used high-throughput sequencing of 16S rRNA genes to characterize the airborne bacterial contribution of a single person sitting in a sanitized custom experimental climate chamber. We compared that to air sampled in an adjacent, identical, unoccupied chamber, as well as to supply and exhaust air sources. Additionally, we assessed microbial communities in settled particles surrounding each occupant, to investigate the potential long-term fate of airborne microbial emissions. Most occupants could be clearly detected by their airborne bacterial emissions, as well as their contribution to settled particles, within 1.5-4 h. Bacterial clouds from the occupants were statistically distinct, allowing the identification of some individual occupants. Our results confirm that an occupied space is microbially distinct from an unoccupied one, and demonstrate for the first time that individuals release their own personalized microbial cloud.}, }
@article {pmid26417154, year = {2015}, author = {Singh, S}, title = {Can Establishment of Human Microbiome be Customized After Birth with Local Traditions of First Feed and Intimate Kissing?.}, journal = {Journal of laboratory physicians}, volume = {7}, number = {2}, pages = {73-74}, pmid = {26417154}, issn = {0974-2727}, }
@article {pmid26409790, year = {2015}, author = {Jun, SR and Robeson, MS and Hauser, LJ and Schadt, CW and Gorin, AA}, title = {PanFP: pangenome-based functional profiles for microbial communities.}, journal = {BMC research notes}, volume = {8}, number = {}, pages = {479}, pmid = {26409790}, issn = {1756-0500}, mesh = {*Algorithms ; Bacteria/*genetics ; Metagenome/*genetics ; Metagenomics/*methods ; Sequence Analysis, DNA ; Statistics, Nonparametric ; }, abstract = {BACKGROUND: For decades there has been increasing interest in understanding the relationships between microbial communities and ecosystem functions. Current DNA sequencing technologies allows for the exploration of microbial communities in two principle ways: targeted rRNA gene surveys and shotgun metagenomics. For large study designs, it is often still prohibitively expensive to sequence metagenomes at both the breadth and depth necessary to statistically capture the true functional diversity of a community. Although rRNA gene surveys provide no direct evidence of function, they do provide a reasonable estimation of microbial diversity, while being a very cost-effective way to screen samples of interest for later shotgun metagenomic analyses. However, there is a great deal of 16S rRNA gene survey data currently available from diverse environments, and thus a need for tools to infer functional composition of environmental samples based on 16S rRNA gene survey data.<br><br>RESULTS: We present a computational method called pangenome-based functional profiles (PanFP), which infers functional profiles of microbial communities from 16S rRNA gene survey data for Bacteria and Archaea. PanFP is based on pangenome reconstruction of a 16S rRNA gene operational taxonomic unit (OTU) from known genes and genomes pooled from the OTU's taxonomic lineage. From this lineage, we derive an OTU functional profile by weighting a pangenome's functional profile with the OTUs abundance observed in a given sample. We validated our method by comparing PanFP to the functional profiles obtained from the direct shotgun metagenomic measurement of 65 diverse communities via Spearman correlation coefficients. These correlations improved with increasing sequencing depth, within the range of 0.8-0.9 for the most deeply sequenced Human Microbiome Project mock community samples. PanFP is very similar in performance to another recently released tool, PICRUSt, for almost all of survey data analysed here. But, our method is unique in that any OTU building method can be used, as opposed to being limited to closed-reference OTU picking strategies against specific reference sequence databases.<br><br>CONCLUSIONS: We developed an automated computational method, which derives an inferred functional profile based on the 16S rRNA gene surveys of microbial communities. The inferred functional profile provides a cost effective way to study complex ecosystems through predicted comparative functional metagenomes and metadata analysis. All PanFP source code and additional documentation are freely available online at GitHub (https://github.com/srjun/PanFP).}, }
@article {pmid26407082, year = {2015}, author = {Ma, ZS}, title = {Power law analysis of the human microbiome.}, journal = {Molecular ecology}, volume = {24}, number = {21}, pages = {5428-5445}, doi = {10.1111/mec.13394}, pmid = {26407082}, issn = {1365-294X}, mesh = {Bacteria/*classification ; Humans ; *Microbiota ; *Models, Biological ; Population Dynamics ; }, abstract = {Taylor's (1961, Nature, 189:732) power law, a power function (V = am(b)) describing the scaling relationship between the mean and variance of population abundances of organisms, has been found to govern the population abundance distributions of single species in both space and time in macroecology. It is regarded as one of few generalities in ecology, and its parameter b has been widely applied to characterize spatial aggregation (i.e. heterogeneity) and temporal stability of single-species populations. Here, we test its applicability to bacterial populations in the human microbiome using extensive data sets generated by the US-NIH Human Microbiome Project (HMP). We further propose extending Taylor's power law from the population to the community level, and accordingly introduce four types of power-law extensions (PLEs): type I PLE for community spatial aggregation (heterogeneity), type II PLE for community temporal aggregation (stability), type III PLE for mixed-species population spatial aggregation (heterogeneity) and type IV PLE for mixed-species population temporal aggregation (stability). Our results show that fittings to the four PLEs with HMP data were statistically extremely significant and their parameters are ecologically sound, hence confirming the validity of the power law at both the population and community levels. These findings not only provide a powerful tool to characterize the aggregations of population and community in both time and space, offering important insights into community heterogeneity in space and/or stability in time, but also underscore the three general properties of power laws (scale invariance, no average and universality) and their specific manifestations in our four PLEs.}, }
@article {pmid26399409, year = {2015}, author = {Praveen, P and Jordan, F and Priami, C and Morine, MJ}, title = {The role of breast-feeding in infant immune system: a systems perspective on the intestinal microbiome.}, journal = {Microbiome}, volume = {3}, number = {}, pages = {41}, pmid = {26399409}, issn = {2049-2618}, mesh = {Biodiversity ; *Breast Feeding ; Cluster Analysis ; Gastrointestinal Microbiome/physiology ; Gene Expression Regulation ; Gene Regulatory Networks ; Humans ; Immune System/*physiology ; Infant ; Metagenome ; Milk, Human/*immunology ; Transcriptome ; }, abstract = {BACKGROUND: The human intestinal microbiota changes from being sparsely populated and variable to possessing a mature, adult-like stable microbiome during the first 2 years of life. This assembly process of the microbiota can lead to either negative or positive effects on health, depending on the colonization sequence and diet. An integrative study on the diet, the microbiota, and genomic activity at the transcriptomic level may give an insight into the role of diet in shaping the human/microbiome relationship. This study aims at better understanding the effects of microbial community and feeding mode (breast-fed and formula-fed) on the immune system, by comparing intestinal metagenomic and transcriptomic data from breast-fed and formula-fed babies.<br><br>RESULTS: We re-analyzed a published metagenomics and host gene expression dataset from a systems biology perspective. Our results show that breast-fed samples co-express genes associated with immunological, metabolic, and biosynthetic activities. The diversity of the microbiota is higher in formula-fed than breast-fed infants, potentially reflecting the weaker dependence of infants on maternal microbiome. We mapped the microbial composition and the expression patterns for host systems and studied their relationship from a systems biology perspective, focusing on the differences.<br><br>CONCLUSIONS: Our findings revealed that there is co-expression of more genes in breast-fed samples but lower microbial diversity compared to formula-fed. Applying network-based systems biology approach via enrichment of microbial species with host genes revealed the novel key relationships of the microbiota with immune and metabolic activity. This was supported statistically by data and literature.}, }
@article {pmid26394469, year = {2015}, author = {Popov, AM and Osipov, AN and Korepanova, EA and Krivoshapko, ON and Shtoda, YP and Klimovich, AA}, title = {[Study of Antioxidant and Membranotropic Activities of Quinazoline Alkaloid Tryptanthrin Using Different Model Systems].}, journal = {Biofizika}, volume = {60}, number = {4}, pages = {700-707}, pmid = {26394469}, issn = {0006-3029}, mesh = {Amidines/chemistry ; Anti-Inflammatory Agents, Non-Steroidal/*chemistry ; Antioxidants/*chemistry ; Ascorbic Acid/chemistry ; Chromans/chemistry ; Drugs, Chinese Herbal/*chemistry ; Hemoglobins/chemistry ; Hydrogen Peroxide/chemistry ; Kinetics ; Lipid Bilayers/chemistry ; Luminescent Measurements ; Luminol/chemistry ; Oxidants/chemistry ; Quercetin/analogs &amp; derivatives/chemistry ; Quinazolines/*chemistry ; }, abstract = {A comparative study of antioxidant (radical-interceptor) properties of tryptanthrin (quinazoline alkaloid shows a high anti-inflammatory activity and it is found in many types of different families of higher plants and microorganisms, including the human microbiome) in the systems of 2,2'-azo-bis(2-methylpropionamidin)dihydrochloride-luminol and hemoglobin-hydrogen peroxide-luminol has been conducted and the influence on the permeability of planar bilayer lipid membranes is evaluated. Trolox was used as a reference antioxidant, and ascorbic acid and dihydroquercetin were taken as standards. Tryptanthrin exhibits very weak antioxidant activity, being markedly inferior to the reference standard and antioxidants while testing antioxidant activity in both studied systems. By the efficacy of antioxidative action the substrates in the systems studied can be arranged in the following order: dihydroquercetin > trolox > ascorbic acid > tryptanthrin. Antioxidant potential of tryptanthrin is approximately 1000 and 3000 times lower than that of trolox and bioflavonoid dihydroquercetine, respectively. Tryptanthrin causes no significant changes in the permeability of planar bilayer membranes in a dose range of 0.5 to. 10 μg/ml. Our data show that tryptanthrin displays no significant radical-interceptor and membranotropic activities. It can be assumed that the observed high anti-inflammatory activity of tryptanthrin is not related to the neutralizing effect against reactive oxygen species and the influence on the permeability of cell membranes. The anticipated mechanisms of biological activity of tryptanthrin are discussed.}, }
@article {pmid26390983, year = {2015}, author = {Balskus, EP}, title = {Colibactin: understanding an elusive gut bacterial genotoxin.}, journal = {Natural product reports}, volume = {32}, number = {11}, pages = {1534-1540}, doi = {10.1039/c5np00091b}, pmid = {26390983}, issn = {1460-4752}, mesh = {Humans ; Molecular Structure ; Mutagens/chemistry/pharmacology ; Peptides/chemistry/*pharmacology ; Polyketides/chemistry/*pharmacology ; }, abstract = {This highlight provides an overview of recent progress towards elucidating the structure, biosynthesis, and mode of action of colibactin, a genotoxic secondary metabolite synthesized by human gut bacteria. While isolating colibactin has been problematic, efforts to characterize its biosynthesis have provided critical information that has led to a rapid increase in our knowledge of this metabolite's structure and function. Major questions and gaps remain however, and the broader lessons learned from studying colibactin underscore central challenges to be faced in the genomics era of natural product research and in efforts to understand the human microbiome.}, }
@article {pmid26388143, year = {2015}, author = {Coelho, ED and Santiago, AM and Arrais, JP and Oliveira, JL}, title = {Computational methodology for predicting the landscape of the human-microbial interactome region level influence.}, journal = {Journal of bioinformatics and computational biology}, volume = {13}, number = {5}, pages = {1550023}, doi = {10.1142/S0219720015500237}, pmid = {26388143}, issn = {1757-6334}, mesh = {*Algorithms ; Computational Biology/*methods ; Computing Methodologies ; Databases, Protein ; Female ; Genetic Variation ; Host-Pathogen Interactions ; Humans ; Male ; Metagenomics/statistics &amp; numerical data ; *Microbiota ; Organ Specificity ; Phylogeny ; Protein Interaction Mapping/*statistics &amp; numerical data ; }, abstract = {Microbial communities thrive in close association among themselves and with the host, establishing protein-protein interactions (PPIs) with the latter, and thus being able to benefit (positively impact) or disturb (negatively impact) biological events in the host. Despite major collaborative efforts to sequence the Human microbiome, there is still a great lack of understanding their impact. We propose a computational methodology to predict the impact of microbial proteins in human biological events, taking into account the abundance of each microbial protein and its relation to all other microbial and human proteins. This alternative methodology is centered on an improved impact estimation algorithm that integrates PPIs between human and microbial proteins with Reactome pathway data. This methodology was applied to study the impact of 24 microbial phyla over different cellular events, within 10 different human microbiomes. The results obtained confirm findings already described in the literature and explore new ones. We believe the Human microbiome can no longer be ignored as not only is there enough evidence correlating microbiome alterations and disease states, but also the return to healthy states once these alterations are reversed.}, }
@article {pmid26387596, year = {2015}, author = {McMillan, A and Rulisa, S and Sumarah, M and Macklaim, JM and Renaud, J and Bisanz, JE and Gloor, GB and Reid, G}, title = {A multi-platform metabolomics approach identifies highly specific biomarkers of bacterial diversity in the vagina of pregnant and non-pregnant women.}, journal = {Scientific reports}, volume = {5}, number = {}, pages = {14174}, pmid = {26387596}, issn = {2045-2322}, support = {//Canadian Institutes of Health Research/Canada ; }, mesh = {Adult ; Biodiversity ; Biomarkers ; Female ; Gardnerella vaginalis/isolation &amp; purification/*metabolism ; Humans ; Lactobacillus/isolation &amp; purification/*metabolism ; Metabolomics ; *Microbiota ; Middle Aged ; Pregnancy ; Rwanda ; Sodium Oxybate/analysis ; Vagina/*microbiology ; Vaginosis, Bacterial/*microbiology ; Valerates/analysis ; Young Adult ; }, abstract = {Bacterial vaginosis (BV) increases transmission of HIV, enhances the risk of preterm labour, and is associated with malodour. Clinical diagnosis often relies on microscopy, which may not reflect the microbiota composition accurately. We use an untargeted metabolomics approach, whereby we normalize the weight of samples prior to analysis, to obtained precise measurements of metabolites in vaginal fluid. We identify biomarkers for BV with high sensitivity and specificity (AUC = 0.99) in a cohort of 131 pregnant and non-pregnant Rwandan women, and demonstrate that the vaginal metabolome is strongly associated with bacterial diversity. Metabolites associated with high diversity and clinical BV include 2-hydroxyisovalerate and γ-hydroxybutyrate (GHB), but not succinate, which is produced by both Lactobacillus crispatus and BV-associated anaerobes in vitro. Biomarkers associated with high diversity and clinical BV are independent of pregnancy status, and were validated in a blinded replication cohort from Tanzania (n = 45), where we predicted clinical BV with 91% accuracy. Correlations between the metabolome and microbiota identified Gardnerella vaginalis as a putative producer of GHB, and we demonstrate production by this species in vitro. This work illustrates how changes in community structure alter the chemical composition of the vagina, and identifies highly specific biomarkers for a common condition.}, }
@article {pmid26385261, year = {2016}, author = {Sandhya, P and Danda, D and Sharma, D and Scaria, V}, title = {Does the buck stop with the bugs?: an overview of microbial dysbiosis in rheumatoid arthritis.}, journal = {International journal of rheumatic diseases}, volume = {19}, number = {1}, pages = {8-20}, doi = {10.1111/1756-185X.12728}, pmid = {26385261}, issn = {1756-185X}, mesh = {Animals ; Anti-Bacterial Agents/therapeutic use ; Arthritis, Rheumatoid/diagnosis/immunology/*microbiology/therapy ; Bacteria/classification/*growth &amp; development/immunology ; Bacterial Translocation ; Diet, Vegetarian ; *Dysbiosis ; Fasting ; *Gastrointestinal Microbiome/drug effects ; Humans ; Intestines/drug effects/immunology/*microbiology ; Joints/drug effects/immunology/*microbiology ; Mouth/drug effects/immunology/*microbiology ; Probiotics/therapeutic use ; }, abstract = {The human body is an environmental niche which is home to diverse co-habiting microbes collectively referred as the human microbiome. Recent years have seen the in-depth characterization of the human microbiome and associations with diseases. Linking of the composition or number of the human microbiota with diseases and traits date back to the original work of Elie Metchnikoff. Recent advances in genomic technologies have opened up finer details and dynamics of this new science with higher precision. Microbe-rheumatoid arthritis connection, largely related to the gut and oral microbiomes, has showed up as a result - apart from several other earlier, well-studied candidate autoimmune diseases. Although evidence favouring roles of specific microbial species, including Porphyromonas, Prevotella and Leptotricha, has become clearer, mechanistic insights still continue to be enigmatic. Manipulating the microbes by traditional dietary modifications, probiotics, and antibiotics and by currently employed disease-modifying agents seems to modulate the disease process and its progression. In the present review, we appraise the existing information as well as the gaps in knowledge in this challenging field. We also discuss the future directions for potential clinical applications, including prevention and management of rheumatoid arthritis using microbial modifications.}, }
@article {pmid26380076, year = {2015}, author = {Larsen, PE and Dai, Y}, title = {Metabolome of human gut microbiome is predictive of host dysbiosis.}, journal = {GigaScience}, volume = {4}, number = {}, pages = {42}, pmid = {26380076}, issn = {2047-217X}, mesh = {Humans ; Intestines/*microbiology ; *Metabolome ; *Microbiota ; Support Vector Machine ; }, abstract = {BACKGROUND: Humans live in constant and vital symbiosis with a closely linked bacterial ecosystem called the microbiome, which influences many aspects of human health. When this microbial ecosystem becomes disrupted, the health of the human host can suffer; a condition called dysbiosis. However, the community compositions of human microbiomes also vary dramatically from individual to individual, and over time, making it difficult to uncover the underlying mechanisms linking the microbiome to human health. We propose that a microbiome's interaction with its human host is not necessarily dependent upon the presence or absence of particular bacterial species, but instead is dependent on its community metabolome; an emergent property of the microbiome.<br><br>RESULTS: Using data from a previously published, longitudinal study of microbiome populations of the human gut, we extrapolated information about microbiome community enzyme profiles and metabolome models. Using machine learning techniques, we demonstrated that the aggregate predicted community enzyme function profiles and modeled metabolomes of a microbiome are more predictive of dysbiosis than either observed microbiome community composition or predicted enzyme function profiles.<br><br>CONCLUSIONS: Specific enzyme functions and metabolites predictive of dysbiosis provide insights into the molecular mechanisms of microbiome-host interactions. The ability to use machine learning to predict dysbiosis from microbiome community interaction data provides a potentially powerful tool for understanding the links between the human microbiome and human health, pointing to potential microbiome-based diagnostics and therapeutic interventions.}, }
@article {pmid26378041, year = {2015}, author = {Ericsson, AC and Akter, S and Hanson, MM and Busi, SB and Parker, TW and Schehr, RJ and Hankins, MA and Ahner, CE and Davis, JW and Franklin, CL and Amos-Landgraf, JM and Bryda, EC}, title = {Differential susceptibility to colorectal cancer due to naturally occurring gut microbiota.}, journal = {Oncotarget}, volume = {6}, number = {32}, pages = {33689-33704}, pmid = {26378041}, issn = {1949-2553}, support = {P40 OD011062/OD/NIH HHS/United States ; T32 OD011126/OD/NIH HHS/United States ; }, mesh = {Animals ; Colorectal Neoplasms/*microbiology/pathology ; Disease Models, Animal ; Disease Susceptibility ; Female ; Gastrointestinal Microbiome ; Humans ; Male ; Rats ; Rats, Inbred F344 ; Rats, Sprague-Dawley ; }, abstract = {Recent studies investigating the human microbiome have identified particular bacterial species that correlate with the presence of colorectal cancer. To evaluate the role of qualitatively different but naturally occurring gut microbiota and the relationship with colorectal cancer development, genetically identical embryos from the Polyposis in Rat Colon (Pirc) rat model of colorectal cancer were transferred into recipients of three different genetic backgrounds (F344/NHsd, LEW/SsNHsd, and Crl:SD). Tumor development in the pups was tracked longitudinally via colonoscopy, and end-stage tumor burden was determined. To confirm vertical transmission and identify associations between the gut microbiota and disease phenotype, the fecal microbiota was characterized in recipient dams 24 hours pre-partum, and in Pirc rat offspring prior to and during disease progression. Our data show that the gut microbiota varies between rat strains, with LEW/SsNHsd having a greater relative abundance of the bacteria Prevotella copri. The mature gut microbiota of pups resembled the profile of their dams, indicating that the dam is the primary determinant of the developing microbiota. Both male and female F344-Pirc rats harboring the Lewis microbiota had decreased tumor burden relative to genetically identical rats harboring F344 or SD microbiota. Significant negative correlations were detected between tumor burden and the relative abundance of specific taxa from samples taken at weaning and shortly thereafter, prior to observable adenoma development. Notably, this naturally occurring variation in the gut microbiota is associated with a significant difference in severity of colorectal cancer, and the abundance of certain taxa is associated with decreased tumor burden.}, }
@article {pmid26377179, year = {2015}, author = {Walsh, CJ and Guinane, CM and Hill, C and Ross, RP and O'Toole, PW and Cotter, PD}, title = {In silico identification of bacteriocin gene clusters in the gastrointestinal tract, based on the Human Microbiome Project's reference genome database.}, journal = {BMC microbiology}, volume = {15}, number = {}, pages = {183}, pmid = {26377179}, issn = {1471-2180}, mesh = {Bacteriocins/*biosynthesis/*genetics ; Biosynthetic Pathways/*genetics ; Computational Biology ; Computer Simulation ; *Gastrointestinal Microbiome ; Gastrointestinal Tract/*microbiology ; Humans ; *Microbiota ; *Multigene Family ; }, abstract = {BACKGROUND: The human gut microbiota comprises approximately 100 trillion microbial cells which significantly impact many aspects of human physiology - including metabolism, nutrient absorption and immune function. Disturbances in this population have been implicated in many conditions and diseases, including obesity, type-2 diabetes and inflammatory bowel disease. This suggests that targeted manipulation or shaping of the gut microbiota, by bacteriocins and other antimicrobials, has potential as a therapeutic tool for the prevention or treatment of these conditions. With this in mind, several studies have used traditional culture-dependent approaches to successfully identify bacteriocin-producers from the mammalian gut. In silico-based approaches to identify novel gene clusters are now also being utilised to take advantage of the vast amount of data currently being generated by next generation sequencing technologies. In this study, we employed an in silico screening approach to mine potential bacteriocin clusters in genome-sequenced isolates from the gastrointestinal tract (GIT). More specifically, the bacteriocin genome-mining tool BAGEL3 was used to identify potential bacteriocin producers in the genomes of the GIT subset of the Human Microbiome Project's reference genome database. Each of the identified gene clusters were manually annotated and potential bacteriocin-associated genes were evaluated.<br><br>RESULTS: We identified 74 clusters of note from 59 unique members of the Firmicutes, Bacteroidetes, Actinobacteria, Fusobacteria and Synergistetes. The most commonly identified class of bacteriocin was the >10&#xa0;kDa class, formerly known as bacteriolysins, followed by lantibiotics and sactipeptides.<br><br>CONCLUSIONS: Multiple bacteriocin gene clusters were identified in a dataset representative of the human gut microbiota. Interestingly, many of these were associated with species and genera which are not typically associated with bacteriocin production.}, }
@article {pmid26374288, year = {2015}, author = {Blekhman, R and Goodrich, JK and Huang, K and Sun, Q and Bukowski, R and Bell, JT and Spector, TD and Keinan, A and Ley, RE and Gevers, D and Clark, AG}, title = {Host genetic variation impacts microbiome composition across human body sites.}, journal = {Genome biology}, volume = {16}, number = {1}, pages = {191}, pmid = {26374288}, issn = {1474-760X}, support = {/WT_/Wellcome Trust/United Kingdom ; R01 DK093595/DK/NIDDK NIH HHS/United States ; T32 GM007617/GM/NIGMS NIH HHS/United States ; U54 HG004969/HG/NHGRI NIH HHS/United States ; }, mesh = {Bacteria/classification/isolation &amp; purification ; *Genetic Variation ; Genome, Human ; Humans ; Metagenomics ; *Microbiota ; }, abstract = {BACKGROUND: The composition of bacteria in and on the human body varies widely across human individuals, and has been associated with multiple health conditions. While microbial communities are influenced by environmental factors, some degree of genetic influence of the host on the microbiome is also expected. This study is part of an expanding effort to comprehensively profile the interactions between human genetic variation and the composition of this microbial ecosystem on a genome- and microbiome-wide scale.<br><br>RESULTS: Here, we jointly analyze the composition of the human microbiome and host genetic variation. By mining the shotgun metagenomic data from the Human Microbiome Project for host DNA reads, we gathered information on host genetic variation for 93 individuals for whom bacterial abundance data are also available. Using this dataset, we identify significant associations between host genetic variation and microbiome composition in 10 of the 15 body sites tested. These associations are driven by host genetic variation in immunity-related pathways, and are especially enriched in host genes that have been previously associated with microbiome-related complex diseases, such as inflammatory bowel disease and obesity-related disorders. Lastly, we show that host genomic regions associated with the microbiome have high levels of genetic differentiation among human populations, possibly indicating host genomic adaptation to environment-specific microbiomes.<br><br>CONCLUSIONS: Our results highlight the role of host genetic variation in shaping the composition of the human microbiome, and provide a starting point toward understanding the complex interaction between human genetics and the microbiome in the context of human evolution and disease.}, }
@article {pmid26372576, year = {2015}, author = {Relman, DA}, title = {The Human Microbiome and the Future Practice of Medicine.}, journal = {JAMA}, volume = {314}, number = {11}, pages = {1127-1128}, doi = {10.1001/jama.2015.10700}, pmid = {26372576}, issn = {1538-3598}, mesh = {Forecasting ; Humans ; Metagenome ; Microbiota/*physiology ; Organ Specificity ; Species Specificity ; }, }
@article {pmid26361503, year = {2015}, author = {Thompson, P and Madan, JC and Moore, JH}, title = {Prediction of relevant biomedical documents: a human microbiome case study.}, journal = {BioData mining}, volume = {8}, number = {}, pages = {28}, pmid = {26361503}, issn = {1756-0381}, support = {P20 GM104416/GM/NIGMS NIH HHS/United States ; R01 LM009012/LM/NLM NIH HHS/United States ; R01 LM010098/LM/NLM NIH HHS/United States ; }, abstract = {BACKGROUND: Retrieving relevant biomedical literature has become increasingly difficult due to the large volume and rapid growth of biomedical publication. A query to a biomedical retrieval system often retrieves hundreds of results. Since the searcher will not likely consider all of these documents, ranking the documents is important. Ranking by recency, as PubMed does, takes into account only one factor indicating potential relevance. This study explores the use of the searcher's relevance feedback judgments to support relevance ranking based on features more general than recency.<br><br>RESULTS: It was found that the researcher's relevance judgments could be used to accurately predict the relevance of additional documents: both using tenfold cross-validation and by training on publications from 2008-2010 and testing on documents from 2011.<br><br>CONCLUSIONS: This case study has shown the promise for relevance feedback to improve biomedical document retrieval. A researcher's judgments as to which initially retrieved documents are relevant, or not, can be leveraged to predict additional relevant documents.}, }
@article {pmid26354806, year = {2015}, author = {Suhr, MJ and Hallen-Adams, HE}, title = {The human gut mycobiome: pitfalls and potentials--a mycologist's perspective.}, journal = {Mycologia}, volume = {107}, number = {6}, pages = {1057-1073}, doi = {10.3852/15-147}, pmid = {26354806}, issn = {0027-5514}, mesh = {Fungi/classification/genetics/*isolation &amp; purification ; *Gastrointestinal Microbiome ; Gastrointestinal Tract/*microbiology ; Humans ; }, abstract = {We have entered the Age of the Microbiome, with new studies appearing constantly and whole journals devoted to the human microbiome. While bacteria outnumber other gut microbes by orders of magnitude, eukaryotes are consistently found in the human gut and are represented primarily by the fungi. Compiling 36 studies 1917-2015 we found at least 267 distinct fungal taxa have been reported from the human gut, and seemingly every new study includes one or more fungi not previously described from this niche. This diversity, while impressive, is illusory. If we examine gut fungi, we will quickly observe a division between a small number of commonly detected species (Candida yeasts, Saccharomyces and yeasts in the Dipodascaceae, and Malassezia species) and a long tail of taxa that have been reported only once. Furthermore, an investigation into the ecology of these rare species reveals that many of them are incapable of colonization or long-term persistence in the gut. This paper examines what we know and have yet to learn about the fungal component of the gut microbiome, or "mycobiome", and an overview of methods. We address the potential of the field while introducing some caveats and argue for the necessity of including mycologists in mycobiome studies.}, }
@article {pmid26342232, year = {2016}, author = {May, A and Brandt, BW and El-Kebir, M and Klau, GW and Zaura, E and Crielaard, W and Heringa, J and Abeln, S}, title = {metaModules identifies key functional subnetworks in microbiome-related disease.}, journal = {Bioinformatics (Oxford, England)}, volume = {32}, number = {11}, pages = {1678-1685}, doi = {10.1093/bioinformatics/btv526}, pmid = {26342232}, issn = {1367-4811}, mesh = {Algorithms ; Dental Caries ; Humans ; *Microbiota ; }, abstract = {MOTIVATION: The human microbiome plays a key role in health and disease. Thanks to comparative metatranscriptomics, the cellular functions that are deregulated by the microbiome in disease can now be computationally explored. Unlike gene-centric approaches, pathway-based methods provide a systemic view of such functions; however, they typically consider each pathway in isolation and in its entirety. They can therefore overlook the key differences that (i) span multiple pathways, (ii) contain bidirectionally deregulated components, (iii) are confined to a pathway region. To capture these properties, computational methods that reach beyond the scope of predefined pathways are needed.<br><br>RESULTS: By integrating an existing module discovery algorithm into comparative metatranscriptomic analysis, we developed metaModules, a novel computational framework for automated identification of the key functional differences between health- and disease-associated communities. Using this framework, we recovered significantly deregulated subnetworks that were indeed recognized to be involved in two well-studied, microbiome-mediated oral diseases, such as butanoate production in periodontal disease and metabolism of sugar alcohols in dental caries. More importantly, our results indicate that our method can be used for hypothesis generation based on automated discovery of novel, disease-related functional subnetworks, which would otherwise require extensive and laborious manual assessment.<br><br>metaModules is available at https://bitbucket.org/alimay/metamodules/<br><br>CONTACT: a.may@vu.nl or s.abeln@vu.nl<br><br>SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.}, }
@article {pmid26336898, year = {2015}, author = {Kumar, V and Kumar, P and Sharma, V}, title = {Xenobiotic and non-xenobiotic interventions in the microbiome therapeutics.}, journal = {Current drug metabolism}, volume = {16}, number = {4}, pages = {284-293}, doi = {10.2174/138920021604150902180008}, pmid = {26336898}, issn = {1875-5453}, mesh = {Animals ; Humans ; *Microbiota ; Probiotics/therapeutic use ; Xenobiotics/*therapeutic use ; }, abstract = {It is now very much clear that the microbiome plays an important part in human health. Microbiome is associated with several diseases and targeting the whole microbiome is certainly a challenge before the scientists. The "Human Microbiome Project" is continually exploring certain therapeutic targets inside microbiome landscape that could be utilized for the treatment of microbiome associated diseases. Additionally, associated research across the globe is going on and now some potential targets are available that might be beneficial for the designing and synthesis of novel drugs. In this review, we made an effort to discuss all the potential targets and corresponding possible drugs/treatments available for each of them. However, it is not possible to treat all microbiome associated diseases with a single drug/drug combination. Therefore, for different diseases, different treatments/drugs (whether xenobiotic or non-xenobiotic) could be used for better therapeutic efficacy.}, }
@article {pmid26336637, year = {2015}, author = {Castro-Nallar, E and Bendall, ML and Pérez-Losada, M and Sabuncyan, S and Severance, EG and Dickerson, FB and Schroeder, JR and Yolken, RH and Crandall, KA}, title = {Composition, taxonomy and functional diversity of the oropharynx microbiome in individuals with schizophrenia and controls.}, journal = {PeerJ}, volume = {3}, number = {}, pages = {e1140}, pmid = {26336637}, issn = {2167-8359}, support = {K12 HL119994/HL/NHLBI NIH HHS/United States ; P50 MH094268/MH/NIMH NIH HHS/United States ; UL1 TR000075/TR/NCATS NIH HHS/United States ; }, abstract = {The role of the human microbiome in schizophrenia remains largely unexplored. The microbiome has been shown to alter brain development and modulate behavior and cognition in animals through gut-brain connections, and research in humans suggests that it may be a modulating factor in many disorders. This study reports findings from a shotgun metagenomic analysis of the oropharyngeal microbiome in 16 individuals with schizophrenia and 16 controls. High-level differences were evident at both the phylum and genus levels, with Proteobacteria, Firmicutes, Bacteroidetes, and Actinobacteria dominating both schizophrenia patients and controls, and Ascomycota being more abundant in schizophrenia patients than controls. Controls were richer in species but less even in their distributions, i.e., dominated by fewer species, as opposed to schizophrenia patients. Lactic acid bacteria were relatively more abundant in schizophrenia, including species of Lactobacilli and Bifidobacterium, which have been shown to modulate chronic inflammation. We also found Eubacterium halii, a lactate-utilizing species. Functionally, the microbiome of schizophrenia patients was characterized by an increased number of metabolic pathways related to metabolite transport systems including siderophores, glutamate, and vitamin B12. In contrast, carbohydrate and lipid pathways and energy metabolism were abundant in controls. These findings suggest that the oropharyngeal microbiome in individuals with schizophrenia is significantly different compared to controls, and that particular microbial species and metabolic pathways differentiate both groups. Confirmation of these findings in larger and more diverse samples, e.g., gut microbiome, will contribute to elucidating potential links between schizophrenia and the human microbiota.}, }
@article {pmid26323626, year = {2015}, author = {Nelson, KE}, title = {An Update on the Status of Current Research on the Mammalian Microbiome.}, journal = {ILAR journal}, volume = {56}, number = {2}, pages = {163-168}, doi = {10.1093/ilar/ilv033}, pmid = {26323626}, issn = {1930-6180}, mesh = {Animals ; Bacteria/metabolism ; Humans ; Mammals/*microbiology ; Microbiota/genetics/*physiology ; Models, Animal ; }, abstract = {The microbiome refers to the thousands of microbial species that inhabit a specific host or environment. Extensive microbiome surveys have been conducted for soils, the built environment, and our oceans. In addition, extensive studies of the human microbiome have revealed significant microbial diversity across all body sites and have hinted at new opportunities for diagnostic and therapeutic approaches to addressing human health and disease. Mammals in general are known to hold a complicated mix of species within their gastrointestinal tracts, including virus, archaea, bacteria, and fungi. These microbial species present beneficial aspects to the host species through the production of vitamins, metabolism of plant structural compounds and sugars, and education of the immune system. In addition to a vast number of studies on humans, studies of the mammalian microbiome have been performed, with several publications on a variety of animal species currently available. These have included studies on the microbiome of companion animals, animals used for research, and animals used for agricultural and food purposes, and various human/animal models.}, }
@article {pmid26323624, year = {2015}, author = {Bleich, A and Fox, JG}, title = {The Mammalian Microbiome and Its Importance in Laboratory Animal Research.}, journal = {ILAR journal}, volume = {56}, number = {2}, pages = {153-158}, pmid = {26323624}, issn = {1930-6180}, support = {P01 CA028842/CA/NCI NIH HHS/United States ; P30 ES002109/ES/NIEHS NIH HHS/United States ; }, mesh = {Animal Experimentation ; Animals ; Animals, Laboratory/metabolism/*microbiology/physiology ; Bacteria/isolation &amp; purification/metabolism ; Mice ; Microbiota/*physiology ; Rats ; }, abstract = {In this issue are assembled 10 fascinating, well-researched papers that describe the emerging field centered on the microbiome of vertebrate animals and how these complex microbial populations play a fundamental role in shaping homeostasis of the host. The content of the papers will deal with bacteria and, because of relative paucity of information on these organisms, will not include discussions on viruses, fungus, protozoa, and parasites that colonize various animals. Dissecting the number and interactions of the 500-1000 bacterial species that can inhabit the intestines of animals is made possible by advanced DNA sequencing methods, which do not depend on whether the organism can be cultured or not. Laboratory animals, particularly rodents, have proven to be an indispensable component in not only understanding how the microbiome aids in digestion and protects the host against pathogens, but also in understanding the relationship of various species of bacteria to development of the immune system. Importantly, this research elucidates purported mechanisms for how the microbiome can profoundly affect initiation and progression of diseases such as type 1 diabetes, metabolic syndromes, obesity, autoimmune arthritis, inflammatory bowel disease, and irritable bowel syndrome. The strengths and limitations of the use of germfree mice colonized with single species of bacteria, a restricted flora, or most recently the use of human-derived microbiota are also discussed.}, }
@article {pmid26318856, year = {2016}, author = {Chen, W and Bao, Y and Chen, X and Burton, J and Gong, X and Gu, D and Mi, Y and Bao, L}, title = {Mycobacterium tuberculosis PE25/PPE41 protein complex induces activation and maturation of dendritic cells and drives Th2-biased immune responses.}, journal = {Medical microbiology and immunology}, volume = {205}, number = {2}, pages = {119-131}, pmid = {26318856}, issn = {1432-1831}, mesh = {Animals ; Antigens, Bacterial/genetics/*immunology ; Antigens, Surface/metabolism ; Bacterial Proteins/immunology ; Cytokines/biosynthesis ; Dendritic Cells/*immunology/metabolism ; Disease Models, Animal ; Female ; Immunity, Humoral ; Immunization ; Lymphocyte Activation ; MAP Kinase Signaling System ; Mice ; Mycobacterium tuberculosis/genetics/*immunology ; NF-kappa B/metabolism ; Recombinant Proteins/immunology ; T-Lymphocyte Subsets/immunology/metabolism ; Th2 Cells/*immunology/metabolism ; Tuberculosis/*immunology/*microbiology ; }, abstract = {Mycobacterium tuberculosis evades innate host immune responses by parasitizing macrophages and causes significant morbidity and mortality around the world. A mycobacterial antigen that can activate dendritic cells (DCs) and elicit effective host innate immune responses will be vital to the development of an effective TB vaccine. The M. tuberculosis genes PE25/PPE41 encode proteins which have been associated with evasion of the host immune response. We constructed a PE25/PPE41 complex gene via splicing by overlapping extension and expressed it successfully in E. coli. We investigated whether this protein complex could interact with DCs to induce effective host immune responses. The PE25/PPE41 protein complex induced maturation of isolated mouse DCs in vitro, increasing expression of cell surface markers (CD80, CD86 and MHC-II), thereby promoting Th2 polarization via secretion of pro-inflammatory cytokines IL-4 and IL-10. In addition, PE25/PPE41 protein complex-activated DCs induced proliferation of mouse CD4(+) and CD8(+) T cells, and a strong humoral response in immunized mice. The sera of five TB patients were also highly reactive to this antigen. These findings suggest that interaction of the PE25/PPE41 protein complex with DCs may be of great immunological significance.}, }
@article {pmid26315909, year = {2015}, author = {Chen, L and Liu, H and Kocher, JP and Li, H and Chen, J}, title = {glmgraph: an R package for variable selection and predictive modeling of structured genomic data.}, journal = {Bioinformatics (Oxford, England)}, volume = {31}, number = {24}, pages = {3991-3993}, pmid = {26315909}, issn = {1367-4811}, support = {P30 ES013508/ES/NIEHS NIH HHS/United States ; }, mesh = {Algorithms ; Genomics/*methods ; Humans ; Linear Models ; Logistic Models ; Microbiota ; Sample Size ; *Software ; }, abstract = {UNLABELLED: One central theme of modern high-throughput genomic data analysis is to identify relevant genomic features as well as build up a predictive model based on selected features for various tasks such as personalized medicine. Correlating the large number of 'omics' features with a certain phenotype is particularly challenging due to small sample size (n) and high dimensionality (p). To address this small n, large p problem, various forms of sparse regression models have been proposed by exploiting the sparsity assumption. Among these, network-constrained sparse regression model is of particular interest due to its ability to utilize the prior graph/network structure in the omics data. Despite its potential usefulness for omics data analysis, no efficient R implementation is publicly available. Here we present an R software package 'glmgraph' that implements the graph-constrained regularization for both sparse linear regression and sparse logistic regression. We implement both the L1 penalty and minimax concave penalty for variable selection and Laplacian penalty for coefficient smoothing. Efficient coordinate descent algorithm is used to solve the optimization problem. We demonstrate the use of the package by applying it to a human microbiome dataset, where phylogeny structure among bacterial taxa is available.<br><br>'glmgraph' is implemented in R and C++ Armadillo and publicly available under CRAN.}, }
@article {pmid26311042, year = {2015}, author = {Hugon, P and Dufour, JC and Colson, P and Fournier, PE and Sallah, K and Raoult, D}, title = {A comprehensive repertoire of prokaryotic species identified in human beings.}, journal = {The Lancet. Infectious diseases}, volume = {15}, number = {10}, pages = {1211-1219}, doi = {10.1016/S1473-3099(15)00293-5}, pmid = {26311042}, issn = {1474-4457}, mesh = {Archaea/*classification/*isolation &amp; purification ; Bacteria/*classification/*isolation &amp; purification ; Bacterial Infections/*microbiology ; Carrier State/*microbiology ; Databases, Factual ; Humans ; *Microbiota ; }, abstract = {The compilation of the complete prokaryotic repertoire associated with human beings as commensals or pathogens is a major goal for the scientific and medical community. The use of bacterial culture techniques remains a crucial step to describe new prokaryotic species. The large number of officially acknowledged bacterial species described since 1980 and the recent increase in the number of recognised pathogenic species have highlighted the absence of an exhaustive compilation of species isolated in human beings. By means of a thorough investigation of several large culture databases and a search of the scientific literature, we built an online database containing all human-associated prokaryotic species described, whether or not they had been validated and have standing in nomenclature. We list 2172 species that have been isolated in human beings. They were classified in 12 different phyla, mostly in the Proteobacteria, Firmicutes, Actinobacteria, and Bacteroidetes phyla. Our online database is useful for both clinicians and microbiologists and forms part of the Human Microbiome Project, which aims to characterise the whole human microbiota and help improve our understanding of the human predisposition and susceptibility to infectious agents.}, }
@article {pmid26309137, year = {2015}, author = {Abeles, SR and Ly, M and Santiago-Rodriguez, TM and Pride, DT}, title = {Effects of Long Term Antibiotic Therapy on Human Oral and Fecal Viromes.}, journal = {PloS one}, volume = {10}, number = {8}, pages = {e0134941}, pmid = {26309137}, issn = {1932-6203}, mesh = {Anti-Bacterial Agents/*adverse effects ; Biodiversity ; Drug Resistance/genetics ; Feces/*virology ; Humans ; Intestines/drug effects/virology ; Microbiota/*drug effects ; Mouth/*drug effects/*virology ; Saliva/drug effects/virology ; Time Factors ; Viruses/*drug effects/genetics ; }, abstract = {Viruses are integral members of the human microbiome. Many of the viruses comprising the human virome have been identified as bacteriophage, and little is known about how they respond to perturbations within the human ecosystem. The intimate association of phage with their cellular hosts suggests their communities may change in response to shifts in bacterial community membership. Alterations to human bacterial biota can result in human disease including a reduction in the host's resilience to pathogens. Here we report the ecology of oral and fecal viral communities and their responses to long-term antibiotic therapy in a cohort of human subjects. We found significant differences between the viral communities of each body site with a more heterogeneous fecal virus community compared with viruses in saliva. We measured the relative diversity of viruses, and found that the oral viromes were significantly more diverse than fecal viromes. There were characteristic changes in the membership of oral and fecal bacterial communities in response to antibiotics, but changes in fecal viral communities were less distinguishing. In the oral cavity, an abundance of papillomaviruses found in subjects on antibiotics suggests an association between antibiotics and papillomavirus production. Despite the abundance of papillomaviruses identified, in neither the oral nor the fecal viromes did antibiotic therapy have any significant impact upon overall viral diversity. There was, however, an apparent expansion of the reservoir of genes putatively involved in resistance to numerous classes of antibiotics in fecal viromes that was not paralleled in oral viromes. The emergence of antibiotic resistance in fecal viromes in response to long-term antibiotic therapy in humans suggests that viruses play an important role in the resilience of human microbial communities to antibiotic disturbances.}, }
@article {pmid26308318, year = {2016}, author = {Fofanova, TY and Petrosino, JF and Kellermayer, R}, title = {Microbiome-Epigenome Interactions and the Environmental Origins of Inflammatory Bowel Diseases.}, journal = {Journal of pediatric gastroenterology and nutrition}, volume = {62}, number = {2}, pages = {208-219}, pmid = {26308318}, issn = {1536-4801}, support = {T32 GM088129/GM/NIGMS NIH HHS/United States ; }, mesh = {*Bacteria ; DNA Methylation ; *Diet ; *Environment ; *Epigenesis, Genetic ; *Genome ; Humans ; Inflammatory Bowel Diseases/*etiology/genetics/microbiology ; *Microbiota ; }, abstract = {The incidence of pediatric inflammatory bowel disease (IBD), which includes Crohn disease and ulcerative colitis, has risen alarmingly in the Western and developing world in recent decades. Epidemiologic (including monozygotic twin and migrant) studies highlight the substantial role of environment and nutrition in IBD etiology. Here we review the literature supporting the developmental and environmental origins hypothesis of IBD. We also provide a detailed exploration of how the human microbiome and epigenome (primarily through DNA methylation) may be important elements in the developmental origins of IBD in both children and adults.}, }
@article {pmid26307544, year = {2015}, author = {Giorgio, C and Mena, P and Del Rio, D and Brighenti, F and Barocelli, E and Hassan-Mohamed, I and Callegari, D and Lodola, A and Tognolini, M}, title = {The ellagitannin colonic metabolite urolithin D selectively inhibits EphA2 phosphorylation in prostate cancer cells.}, journal = {Molecular nutrition &amp; food research}, volume = {59}, number = {11}, pages = {2155-2167}, doi = {10.1002/mnfr.201500470}, pmid = {26307544}, issn = {1613-4133}, mesh = {Anticarcinogenic Agents/*pharmacology ; Cell Line, Tumor ; Cell Proliferation/drug effects ; Coumarins/*pharmacology ; Humans ; Hydrolyzable Tannins/metabolism ; Male ; Models, Molecular ; Molecular Dynamics Simulation ; Phosphorylation ; Prostatic Neoplasms/*pathology ; Receptor, EphA2/*antagonists &amp; inhibitors/chemistry/metabolism ; }, abstract = {SCOPE: The Eph-ephrin system comprises emerging proteins involved in many pathophysiological processes. The pharmacological activity of the main metabolites derived from the intake of some classes of (poly)phenolic compounds, such as caffeoylquinic acids, flavan-3-ols, and ellagitannins, on the Eph-ephrin interaction was evaluated at physiological concentrations. Functional studies to elucidate their role in prostate cancer were also performed.<br><br>METHODS AND RESULTS: Among the 21 phenolics screened by an ELISA-binding assay, just urolithin C, urolithin D, and ellagic acid succeeded to inhibit the EphA2-ephrin-A1 binding. Urolithin D, the most active, was a competitive and reversible antagonist of EphA receptors able to discriminate between EphA and EphB receptors, showing intra-classes selectivity. Molecular modeling and structure-activity relationships shed light on the binding mode and selective activity of urolithin D. This catabolite blocked EphA2 phosphorylation mediated by ephrin-A1, while lacking cytotoxicity and anti-proliferative effects, and was inactive on the EphA2 kinase assay.<br><br>CONCLUSION: The mechanisms behind the cancer preventive properties of foods rich in flavan-3-ols and caffeoylquinic acids are not associated with metabolic pathways directly linked to the Eph-ephrin system. However, the ellagitannin-derived colonic metabolite urolithin D was able to exert remarkable and selective EphA-ephrin-A inhibition, which might impact on prostate cancer prevention.}, }
@article {pmid26305138, year = {2015}, author = {Baumgart, DC}, title = {[The human microbiome].}, journal = {Deutsche medizinische Wochenschrift (1946)}, volume = {140}, number = {19}, pages = {1451-1456}, doi = {10.1055/s-0041-103202}, pmid = {26305138}, issn = {1439-4413}, mesh = {Clostridioides difficile ; Clostridium Infections ; Fecal Microbiota Transplantation ; Humans ; *Microbiota ; }, abstract = {Research into the human microbiome will substantially enhance our understanding of inflammatory, metabolic and malignant diseases. The complexity of this research area can only be addressed by an interdisciplinary translational approach including bioinformatics. Data derived from pure in silico analyses and statistical associations will not automatically translate into sound clinical concepts, as we have learned previously in genetics. Potential targets for future treatment strategies include the proven impact of nutrition and medication on microbial diversity and therapeutic effects of microbial metabolic processes and metabolites. Fecal microbial transplantation (FMT) beyond its indication in refractory Clostridium difficile infection (CDI) should be held against the same standards and regulated by the same procedures that are applied to all investigational compounds and treatments prior to their approval. Donor fidelity, sample processing and recipient safety (including the role of fecal pathogens and toxins) need thorough scientific investigation and evaluation in clinical trials with objective outcome parameters prior to any recommendations for clinical practice.}, }
@article {pmid26301122, year = {2015}, author = {Malnick, S and Melzer, E}, title = {Human microbiome: From the bathroom to the bedside.}, journal = {World journal of gastrointestinal pathophysiology}, volume = {6}, number = {3}, pages = {79-85}, pmid = {26301122}, issn = {2150-5330}, abstract = {The human gut contains trillions of bacteria, the major phylae of which include Bacteroidetes, Firmicutes, Actinobacteria and Proteobacteria. Fecal microbial transplantation (FMT) has been known of for many years but only recently has been subjected to rigorous examination. We review the evidence regarding FMT for recurrent Clostridium difficile infection which has resulted in it being an approved treatment. In addition there is some evidence for its use in both irritable bowel syndrome and inflammatory bowel disease. Further research is needed in order to define the indications for FMT and the most appropriate method of administration.}, }
@article {pmid26297702, year = {2015}, author = {Cottier, F and Tan, AS and Xu, X and Wang, Y and Pavelka, N}, title = {MIG1 Regulates Resistance of Candida albicans against the Fungistatic Effect of Weak Organic Acids.}, journal = {Eukaryotic cell}, volume = {14}, number = {10}, pages = {1054-1061}, pmid = {26297702}, issn = {1535-9786}, mesh = {Acetic Acid/*pharmacology ; Antifungal Agents/*pharmacology ; Butyric Acid/*pharmacology ; Candida albicans/drug effects/genetics/*growth &amp; development ; Candidiasis/microbiology ; Drug Resistance, Fungal/genetics ; Fungal Proteins/genetics/*metabolism ; Lactic Acid/*pharmacology ; Microbial Sensitivity Tests ; Propionates/*pharmacology ; Repressor Proteins/genetics/*metabolism ; }, abstract = {Candida albicans is the leading cause of fungal infections; but it is also a member of the human microbiome, an ecosystem of thousands of microbial species potentially influencing the outcome of host-fungal interactions. Accordingly, antibacterial therapy raises the risk of candidiasis, yet the underlying mechanism is currently not fully understood. We hypothesize the existence of bacterial metabolites that normally control C. albicans growth and of fungal resistance mechanisms against these metabolites. Among the most abundant microbiota-derived metabolites found on human mucosal surfaces are weak organic acids (WOAs), such as acetic, propionic, butyric, and lactic acid. Here, we used quantitative growth assays to investigate the dose-dependent fungistatic properties of WOAs on C. albicans growth and found inhibition of growth to occur at physiologically relevant concentrations and pH values. This effect was conserved across distantly related fungal species both inside and outside the CTG clade. We next screened a library of transcription factor mutants and identified several genes required for the resistance of C. albicans to one or more WOAs. A single gene, MIG1, previously known for its role in glucose repression, conferred resistance against all four acids tested. Consistent with glucose being an upstream activator of Mig1p, the presence of this carbon source was required for WOA resistance in wild-type C. albicans. Conversely, a MIG1-complemented strain completely restored the glucose-dependent resistance against WOAs. We conclude that Mig1p plays a central role in orchestrating a transcriptional program to fight against the fungistatic effect of this class of highly abundant metabolites produced by the gastrointestinal tract microbiota.}, }
@article {pmid26292041, year = {2016}, author = {Barnett, C and Nazzal, L and Goldfarb, DS and Blaser, MJ}, title = {The Presence of Oxalobacter formigenes in the Microbiome of Healthy Young Adults.}, journal = {The Journal of urology}, volume = {195}, number = {2}, pages = {499-506}, pmid = {26292041}, issn = {1527-3792}, support = {U54 DK083908/DK/NIDDK NIH HHS/United States ; P30 CA016087/CA/NCI NIH HHS/United States ; UH2 AR057506/AR/NIAMS NIH HHS/United States ; U54 DK 083908/DK/NIDDK NIH HHS/United States ; R01 DK090989/DK/NIDDK NIH HHS/United States ; }, mesh = {Adolescent ; Adult ; Feces/microbiology ; Female ; Healthy Volunteers ; Humans ; Male ; Metagenome/genetics ; *Microbiota ; Oxalobacter formigenes/classification/genetics/*isolation &amp; purification ; United States ; }, abstract = {PURPOSE: Oxalobacter formigenes, a member of the human colonic microbiota with a major role in net colonic oxalate transport and secretion, is protective against the formation of calcium oxalate kidney stones. We describe the prevalence, relative abundance and stability of O. formigenes in healthy young adults in the United States.<br><br>MATERIALS AND METHODS: We used HMP (Human Microbiome Project) data on fecal samples from 242 healthy young adults who had 1 to 3 study visits. Samples underwent whole genomic shotgun sequencing and/or 16S rRNA sequencing. Three data sets available from the processed sequence data were studied, including whole genomic shotgun metagenomic analysis by alignment to reference genomes using shotgun community profiling, or MetaPhlAn (http://huttenhower.sph.harvard.edu/metaphlan) or QIIME (http://qiime.org/) analysis of the V1-3 or V3-5 16S sequences.<br><br>RESULTS: O. formigenes was detected in fecal samples using whole genomic shotgun and 16S rRNA data. Analysis of the whole genomic shotgun data set using shotgun community profiling showed that 29 of 94 subjects (31%) were O. formigenes positive. V1-3 and V3-5 analyses were less sensitive for O. formigenes detection. When present, O. formigenes relative abundance varied over 3 log10 and was normally distributed. All assays agreed in 58 of 66 samples (88%) studied by all 3 methods. Of 14 subjects who were O. formigenes positive at baseline 13 (93%) were positive at the followup visit, indicating the stability of colonization.<br><br>CONCLUSIONS: O. formigenes appears to be stably present in fewer than half of healthy young adults in the United States. It is most sensitively detected by whole genomic shotgun.}, }
@article {pmid26283367, year = {2015}, author = {Cohen, LJ and Kang, HS and Chu, J and Huang, YH and Gordon, EA and Reddy, BV and Ternei, MA and Craig, JW and Brady, SF}, title = {Functional metagenomic discovery of bacterial effectors in the human microbiome and isolation of commendamide, a GPCR G2A/132 agonist.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {112}, number = {35}, pages = {E4825-34}, pmid = {26283367}, issn = {1091-6490}, support = {UL1 TR000043/TR/NCATS NIH HHS/United States ; GM077516/GM/NIGMS NIH HHS/United States ; T32GM07739/GM/NIGMS NIH HHS/United States ; T32 DK007792/DK/NIDDK NIH HHS/United States ; R01 GM077516/GM/NIGMS NIH HHS/United States ; //Howard Hughes Medical Institute/United States ; T32 GM007739/GM/NIGMS NIH HHS/United States ; }, mesh = {DNA/genetics ; Glycine/*analogs &amp; derivatives/pharmacology ; HEK293 Cells ; Humans ; *Metagenomics ; *Microbiota ; Microscopy, Fluorescence ; Molecular Sequence Data ; Palmitates/*pharmacology ; Phylogeny ; Receptors, G-Protein-Coupled/*agonists ; }, abstract = {The trillions of bacteria that make up the human microbiome are believed to encode functions that are important to human health; however, little is known about the specific effectors that commensal bacteria use to interact with the human host. Functional metagenomics provides a systematic means of surveying commensal DNA for genes that encode effector functions. Here, we examine 3,000 Mb of metagenomic DNA cloned from three phenotypically distinct patients for effectors that activate NF-κB, a transcription factor known to play a central role in mediating responses to environmental stimuli. This screen led to the identification of 26 unique commensal bacteria effector genes (Cbegs) that are predicted to encode proteins with diverse catabolic, anabolic, and ligand-binding functions and most frequently interact with either glycans or lipids. Detailed analysis of one effector gene family (Cbeg12) recovered from all three patient libraries found that it encodes for the production of N-acyl-3-hydroxypalmitoyl-glycine (commendamide). This metabolite was also found in culture broth from the commensal bacterium Bacteroides vulgatus, which harbors a gene highly similar to Cbeg12. Commendamide resembles long-chain N-acyl-amides that function as mammalian signaling molecules through activation of G-protein-coupled receptors (GPCRs), which led us to the observation that commendamide activates the GPCR G2A/GPR132. G2A has been implicated in disease models of autoimmunity and atherosclerosis. This study shows the utility of functional metagenomics for identifying potential mechanisms used by commensal bacteria for host interactions and outlines a functional metagenomics-based pipeline for the systematic identification of diverse commensal bacteria effectors that impact host cellular functions.}, }
@article {pmid26278471, year = {2015}, author = {Edmonds-Wilson, SL and Nurinova, NI and Zapka, CA and Fierer, N and Wilson, M}, title = {Review of human hand microbiome research.}, journal = {Journal of dermatological science}, volume = {80}, number = {1}, pages = {3-12}, doi = {10.1016/j.jdermsci.2015.07.006}, pmid = {26278471}, issn = {1873-569X}, mesh = {Hand/*microbiology ; Humans ; *Microbiota ; Skin/*microbiology ; }, abstract = {Recent advances have increased our understanding of the human microbiome, including the skin microbiome. Despite the importance of the hands as a vector for infection transmission, there have been no comprehensive reviews of recent advances in hand microbiome research or overviews of the factors that influence the composition of the hand microbiome. A comprehensive and systematic database search was conducted for skin microbiome-related articles published from January 1, 2008 to April 1, 2015. Only primary research articles that used culture-independent, whole community analysis methods to study the healthy hand skin microbiome were included. Eighteen articles were identified containing hand microbiome data. Most focused on bacteria, with relatively little reported on fungi, viruses, and protozoa. Bacteria from four phyla were found across all studies of the hand microbiome (most to least relative abundance): Firmicutes, Actinobacteria, Proteobacteria, Bacteroidetes. Key factors that impacted the hand microbiome composition included temporal and biogeographical dynamics, as well as intrinsic (age, gender) and extrinsic (product use, cohabitants, pet-ownership) variables. There was more temporal variability in the composition of the hand microbiome than in other body sites, making identification of the "normal" microbiome of the hands challenging. The microbiome of the hands is in constant flux as the hands are a critical vector for transmitting microorganisms between people, pets, inanimate objects and our environments. Future studies need to resolve methodological influences on results, and further investigate factors which alter the hand microbiome including the impact of products applied to hands. Increased understanding of the hand microbiome and the skin microbiome in general, will open the door to product development for disease prevention and treatment, and may lead to other applications, including novel diagnostic and forensic approaches.}, }
@article {pmid26271741, year = {2016}, author = {Bataille, A and Lee-Cruz, L and Tripathi, B and Kim, H and Waldman, B}, title = {Microbiome Variation Across Amphibian Skin Regions: Implications for Chytridiomycosis Mitigation Efforts.}, journal = {Microbial ecology}, volume = {71}, number = {1}, pages = {221-232}, pmid = {26271741}, issn = {1432-184X}, mesh = {Animals ; Anura/*microbiology ; Bacteria/classification/genetics/*isolation &amp; purification ; Biodiversity ; Chytridiomycota/*physiology ; *Microbiota ; Mycoses/microbiology/*veterinary ; Skin/*microbiology ; }, abstract = {Cutaneous bacteria may play an important role in the resistance of amphibians to the pathogenic fungus Batrachochytrium dendrobatidis (Bd). Microbial communities resident on hosts' skin show topographical diversity mapping to skin features, as demonstrated by studies of the human microbiome. We examined skin microbiomes of wild and captive fire-bellied toads (Bombina orientalis) for differences across their body surface. We found that bacterial communities differed between ventral and dorsal skin. Wild toads showed slightly higher bacterial richness and diversity in the dorsal compared to the ventral region. On the other hand, captive toads hosted a higher richness and diversity of bacteria on their ventral than their dorsal skin. Microbial community composition and relative abundance of major bacterial taxonomic groups also differed between ventral and dorsal skin in all populations. Furthermore, microbiome diversity patterns varied as a function of their Bd infection status in wild toads. Bacterial richness and diversity was greater, and microbial community structure more complex, in wild than captive toads. The results suggest that bacterial community structure is influenced by microhabitats associated with skin regions. These local communities may be differentially modified when interacting with environmental bacteria and Bd. A better understanding of microbiome variation across skin regions will be needed to assess how the skin microbiota affects the abilities of amphibian hosts to resist Bd infection, especially in captive breeding programs.}, }
@article {pmid26266269, year = {2015}, author = {Bonamichi-Santos, R and Aun, MV and Agondi, RC and Kalil, J and Giavina-Bianchi, P}, title = {Microbiome and Asthma: What Have Experimental Models Already Taught Us?.}, journal = {Journal of immunology research}, volume = {2015}, number = {}, pages = {614758}, pmid = {26266269}, issn = {2314-7156}, mesh = {Allergens/immunology ; Animals ; Asthma/*etiology ; Disease Models, Animal ; Environmental Microbiology ; Gastrointestinal Microbiome ; Humans ; Mice ; *Microbiota ; Research ; Respiratory Mucosa/microbiology ; }, abstract = {Asthma is a chronic inflammatory disease that imposes a substantial burden on patients, their families, and the community. Although many aspects of the pathogenesis of classical allergic asthma are well known by the scientific community, other points are not yet understood. Experimental asthma models, particularly murine models, have been used for over 100 years in order to better understand the immunopathology of asthma. It has been shown that human microbiome is an important component in the development of the immune system. Furthermore, the occurrence of many inflammatory diseases is influenced by the presence of microbes. Again, experimental models of asthma have helped researchers to understand the relationship between the microbiome and respiratory inflammation. In this review, we discuss the evolution of murine models of asthma and approach the major studies involving the microbiome and asthma.}, }
@article {pmid26259788, year = {2015}, author = {Bengtsson-Palme, J and Angelin, M and Huss, M and Kjellqvist, S and Kristiansson, E and Palmgren, H and Larsson, DG and Johansson, A}, title = {The Human Gut Microbiome as a Transporter of Antibiotic Resistance Genes between Continents.}, journal = {Antimicrobial agents and chemotherapy}, volume = {59}, number = {10}, pages = {6551-6560}, pmid = {26259788}, issn = {1098-6596}, mesh = {Adult ; Anti-Bacterial Agents/*pharmacology ; Drug Resistance, Microbial/*genetics ; Escherichia coli/drug effects ; Feces/microbiology ; Female ; Gastrointestinal Microbiome/*genetics ; Humans ; Male ; Metagenomics ; Microbial Sensitivity Tests ; Proteobacteria/drug effects/genetics ; Sulfonamides/pharmacology ; Trimethoprim/pharmacology ; Young Adult ; beta-Lactams/pharmacology ; }, abstract = {Previous studies of antibiotic resistance dissemination by travel have, by targeting only a select number of cultivable bacterial species, omitted most of the human microbiome. Here, we used explorative shotgun metagenomic sequencing to address the abundance of >300 antibiotic resistance genes in fecal specimens from 35 Swedish students taken before and after exchange programs on the Indian peninsula or in Central Africa. All specimens were additionally cultured for extended-spectrum beta-lactamase (ESBL)-producing enterobacteria, and the isolates obtained were genome sequenced. The overall taxonomic diversity and composition of the gut microbiome remained stable before and after travel, but there was an increasing abundance of Proteobacteria in 25/35 students. The relative abundance of antibiotic resistance genes increased, most prominently for genes encoding resistance to sulfonamide (2.6-fold increase), trimethoprim (7.7-fold), and beta-lactams (2.6-fold). Importantly, the increase observed occurred without any antibiotic intake. Of 18 students visiting the Indian peninsula, 12 acquired ESBL-producing Escherichia coli, while none returning from Africa were positive. Despite deep sequencing efforts, the sensitivity of metagenomics was not sufficient to detect acquisition of the low-abundant genes responsible for the observed ESBL phenotype. In conclusion, metagenomic sequencing of the intestinal microbiome of Swedish students returning from exchange programs in Central Africa or the Indian peninsula showed increased abundance of genes encoding resistance to widely used antibiotics.}, }
@article {pmid26252519, year = {2015}, author = {Gorzelak, MA and Gill, SK and Tasnim, N and Ahmadi-Vand, Z and Jay, M and Gibson, DL}, title = {Methods for Improving Human Gut Microbiome Data by Reducing Variability through Sample Processing and Storage of Stool.}, journal = {PloS one}, volume = {10}, number = {8}, pages = {e0134802}, pmid = {26252519}, issn = {1932-6203}, mesh = {Bacteria/classification ; DNA/metabolism ; Feces/*microbiology ; Freezing ; *Gastrointestinal Microbiome ; Humans ; *Preservation, Biological ; RNA/metabolism ; Real-Time Polymerase Chain Reaction ; Specimen Handling/*methods ; Temperature ; }, abstract = {Gut microbiome community analysis is used to understand many diseases like inflammatory bowel disease, obesity, and diabetes. Sampling methods are an important consideration for human microbiome research, yet are not emphasized in many studies. In this study, we demonstrate that the preparation, handling, and storage of human faeces are critical processes that alter the outcomes of downstream DNA-based bacterial community analyses via qPCR. We found that stool subsampling resulted in large variability of gut microbiome data due to different microenvironments harbouring various taxa within an individual stool. However, we reduced intra-sample variability by homogenizing the entire stool sample in liquid nitrogen and subsampling from the resulting crushed powder prior to DNA extraction. We experimentally determined that the bacterial taxa varied with room temperature storage beyond 15 minutes and beyond three days storage in a domestic frost-free freezer. While freeze thawing only had an effect on bacterial taxa abundance beyond four cycles, the use of samples stored in RNAlater should be avoided as overall DNA yields were reduced as well as the detection of bacterial taxa. Overall we provide solutions for processing and storing human stool samples that reduce variability of microbiome data. We recommend that stool is frozen within 15 minutes of being defecated, stored in a domestic frost-free freezer for less than three days, and homogenized prior to DNA extraction. Adoption of these simple protocols will have a significant and positive impact on future human microbiome research.}, }
@article {pmid26248263, year = {2015}, author = {Rogers, GB}, title = {Germs and joints: the contribution of the human microbiome to rheumatoid arthritis.}, journal = {Nature medicine}, volume = {21}, number = {8}, pages = {839-841}, pmid = {26248263}, issn = {1546-170X}, mesh = {Arthritis, Rheumatoid/*microbiology ; Humans ; Intestines/*microbiology ; *Microbiota ; Mouth/*microbiology ; }, }
@article {pmid26246894, year = {2015}, author = {Wang, Q and Fish, JA and Gilman, M and Sun, Y and Brown, CT and Tiedje, JM and Cole, JR}, title = {Xander: employing a novel method for efficient gene-targeted metagenomic assembly.}, journal = {Microbiome}, volume = {3}, number = {}, pages = {32}, pmid = {26246894}, issn = {2049-2618}, support = {P42 ES004911/ES/NIEHS NIH HHS/United States ; }, abstract = {BACKGROUND: Metagenomics can provide important insight into microbial communities. However, assembling metagenomic datasets has proven to be computationally challenging. Current methods often assemble only fragmented partial genes.<br><br>RESULTS: We present a novel method for targeting assembly of specific protein-coding genes. This method combines a de Bruijn graph, as used in standard assembly approaches, and a protein profile hidden Markov model (HMM) for the gene of interest, as used in standard annotation approaches. These are used to create a novel combined weighted assembly graph. Xander performs both assembly and annotation concomitantly using information incorporated in this graph. We demonstrate the utility of this approach by assembling contigs for one phylogenetic marker gene and for two functional marker genes, first on Human Microbiome Project (HMP)-defined community Illumina data and then on 21 rhizosphere soil metagenomic datasets from three different crops totaling over 800&#xa0;Gbp of unassembled data. We compared our method to a recently published bulk metagenome assembly method and a recently published gene-targeted assembler and found our method produced more, longer, and higher quality gene sequences.<br><br>CONCLUSION: Xander combines gene assignment with the rapid assembly of full-length or near full-length functional genes from metagenomic data without requiring bulk assembly or post-processing to find genes of interest. HMMs used for assembly can be tailored to the targeted genes, allowing flexibility to improve annotation over generic annotation pipelines. This method is implemented as open source software and is available at https://github.com/rdpstaff/Xander_assembler.}, }
@article {pmid26243526, year = {2015}, author = {Dixon, EF and Hall, RA}, title = {Noisy neighbourhoods: quorum sensing in fungal-polymicrobial infections.}, journal = {Cellular microbiology}, volume = {17}, number = {10}, pages = {1431-1441}, pmid = {26243526}, issn = {1462-5822}, support = {MR/L00903X/1//Medical Research Council/United Kingdom ; }, mesh = {Coinfection/*microbiology ; Fungi/growth &amp; development/metabolism/*physiology ; Mycoses/*microbiology ; *Quorum Sensing ; }, abstract = {Quorum sensing was once considered a way in which a species was able to sense its cell density and regulate gene expression accordingly. However, it is now becoming apparent that multiple microbes can sense particular quorum-sensing molecules, enabling them to sense and respond to other microbes in their neighbourhood. Such interactions are significant within the context of polymicrobial disease, in which the competition or cooperation of microbes can alter disease progression. Fungi comprise a small but important component of the human microbiome and are in constant contact with bacteria and viruses. The discovery of quorum-sensing pathways in fungi has led to the characterization of a number of interkingdom quorum-sensing interactions. Here, we review the recent developments in quorum sensing in medically important fungi, and the implications these interactions have on the host's innate immune response.}, }
@article {pmid26239804, year = {2015}, author = {Mullane, K and Williams, M}, title = {Unknown unknowns in biomedical research: does an inability to deal with ambiguity contribute to issues of irreproducibility?.}, journal = {Biochemical pharmacology}, volume = {97}, number = {2}, pages = {133-136}, doi = {10.1016/j.bcp.2015.07.002}, pmid = {26239804}, issn = {1873-2968}, mesh = {Age Factors ; Biomedical Research/*standards ; Humans ; Peer Review, Research/*standards ; Reproducibility of Results ; }, abstract = {The credibility and consequent sustainability of the biomedical research "ecosystem" is in jeopardy, in part due to an inability to reproduce data from the peer-reviewed literature. Despite obvious and relatively inexpensive solutions to improve reproducibility-ensuring that experimental reagents, specifically cancer cell lines and antibodies, are authenticated/validated before use and that best practices in statistical usage are incorporated into the design, analysis, and reporting of experiments-these are routinely ignored, a reflection of hubris and a comfort with the status quo on the part of many investigators. New guidelines for the peer review of publications and grant applications introduced in the past year, while well-intended, lack the necessary consequences, e.g., denial of funding, that would result in sustained improvements when scientific rigor is lacking and/or transparency is, at best, opaque. An additional factor contributing to irreproducibility is a reductionist mindset that prioritizes certainty in research outcomes over the ambiguity intrinsic to biological systems that is often reflected in "unknown unknowns". This has resulted in a tendency towards codifying "rules" that can provide "yes-no" outcomes that represent a poor substitute for the intellectual challenge and skepticism that leads to an awareness and consideration of "unknown unknowns". When acknowledged as potential causes of unexpected experimental outcomes, these can often transition into the "knowns" that facilitate positive, disruptive innovation in biomedical research like the human microbiome. Changes in investigator mindset, both in terms of validating reagents and embracing ambiguity, are necessary to aid in reducing issues with reproducibility.}, }
@article {pmid26229982, year = {2015}, author = {Clemente, JC and Pehrsson, EC and Blaser, MJ and Sandhu, K and Gao, Z and Wang, B and Magris, M and Hidalgo, G and Contreras, M and Noya-Alarcón, &#xd3; and Lander, O and McDonald, J and Cox, M and Walter, J and Oh, PL and Ruiz, JF and Rodriguez, S and Shen, N and Song, SJ and Metcalf, J and Knight, R and Dantas, G and Dominguez-Bello, MG}, title = {The microbiome of uncontacted Amerindians.}, journal = {Science advances}, volume = {1}, number = {3}, pages = {}, pmid = {26229982}, issn = {2375-2548}, support = {DP2 DK098089/DK/NIDDK NIH HHS/United States ; P30 CA016087/CA/NCI NIH HHS/United States ; R01 GM099538/GM/NIGMS NIH HHS/United States ; U24 DK062429/DK/NIDDK NIH HHS/United States ; UH2 AR057506/AR/NIAMS NIH HHS/United States ; U01 DK062429/DK/NIDDK NIH HHS/United States ; R25 GM061151/GM/NIGMS NIH HHS/United States ; }, abstract = {Most studies of the human microbiome have focused on westernized people with life-style practices that decrease microbial survival and transmission, or on traditional societies that are currently in transition to westernization. We characterize the fecal, oral, and skin bacterial microbiome and resistome of members of an isolated Yanomami Amerindian village with no documented previous contact with Western people. These Yanomami harbor a microbiome with the highest diversity of bacteria and genetic functions ever reported in a human group. Despite their isolation, presumably for >11,000 years since their ancestors arrived in South America, and no known exposure to antibiotics, they harbor bacteria that carry functional antibiotic resistance (AR) genes, including those that confer resistance to synthetic antibiotics and are syntenic with mobilization elements. These results suggest that westernization significantly affects human microbiome diversity and that functional AR genes appear to be a feature of the human microbiome even in the absence of exposure to commercial antibiotics. AR genes are likely poised for mobilization and enrichment upon exposure to pharmacological levels of antibiotics. Our findings emphasize the need for extensive characterization of the function of the microbiome and resistome in remote nonwesternized populations before globalization of modern practices affects potentially beneficial bacteria harbored in the human body.}, }
@article {pmid26222383, year = {2015}, author = {Beasley, DE and Koltz, AM and Lambert, JE and Fierer, N and Dunn, RR}, title = {The Evolution of Stomach Acidity and Its Relevance to the Human Microbiome.}, journal = {PloS one}, volume = {10}, number = {7}, pages = {e0134116}, pmid = {26222383}, issn = {1932-6203}, mesh = {Animals ; *Biological Evolution ; Birds ; Food Microbiology ; Gastric Acid/*physiology ; *Gastrointestinal Microbiome ; Herbivory ; Host-Pathogen Interactions ; Humans ; Hydrogen-Ion Concentration ; Mammals ; Phylogeny ; Stomach/microbiology/physiology ; Symbiosis ; }, abstract = {Gastric acidity is likely a key factor shaping the diversity and composition of microbial communities found in the vertebrate gut. We conducted a systematic review to test the hypothesis that a key role of the vertebrate stomach is to maintain the gut microbial community by filtering out novel microbial taxa before they pass into the intestines. We propose that species feeding either on carrion or on organisms that are close phylogenetic relatives should require the most restrictive filter (measured as high stomach acidity) as protection from foreign microbes. Conversely, species feeding on a lower trophic level or on food that is distantly related to them (e.g. herbivores) should require the least restrictive filter, as the risk of pathogen exposure is lower. Comparisons of stomach acidity across trophic groups in mammal and bird taxa show that scavengers and carnivores have significantly higher stomach acidities compared to herbivores or carnivores feeding on phylogenetically distant prey such as insects or fish. In addition, we find when stomach acidity varies within species either naturally (with age) or in treatments such as bariatric surgery, the effects on gut bacterial pathogens and communities are in line with our hypothesis that the stomach acts as an ecological filter. Together these results highlight the importance of including measurements of gastric pH when investigating gut microbial dynamics within and across species.}, }
@article {pmid26220947, year = {2016}, author = {Rodrigues Hoffmann, A and Proctor, LM and Surette, MG and Suchodolski, JS}, title = {The Microbiome: The Trillions of Microorganisms That Maintain Health and Cause Disease in Humans and Companion Animals.}, journal = {Veterinary pathology}, volume = {53}, number = {1}, pages = {10-21}, doi = {10.1177/0300985815595517}, pmid = {26220947}, issn = {1544-2217}, mesh = {Animals ; Gastrointestinal Tract/microbiology ; Humans ; Lung/microbiology ; *Microbiota ; Pets ; Respiratory System/microbiology ; Skin/microbiology ; }, abstract = {The microbiome is the complex collection of microorganisms, their genes, and their metabolites, colonizing the human and animal mucosal surfaces, digestive tract, and skin. It is now well known that the microbiome interacts with its host, assisting in digestion and detoxification, supporting immunity, protecting against pathogens, and maintaining health. Studies published to date have demonstrated that healthy individuals are often colonized with different microbiomes than those with disease involving various organ systems. This review covers a brief history of the development of the microbiome field, the main objectives of the Human Microbiome Project, and the most common microbiomes inhabiting the human respiratory tract, companion animal digestive tract, and skin in humans and companion animals. The main changes in the microbiomes in patients with pulmonary, gastrointestinal, and cutaneous lesions are described.}, }
@article {pmid26215258, year = {2015}, author = {Santiago-Rodriguez, TM and Naidu, M and Abeles, SR and Boehm, TK and Ly, M and Pride, DT}, title = {Transcriptome analysis of bacteriophage communities in periodontal health and disease.}, journal = {BMC genomics}, volume = {16}, number = {1}, pages = {549}, pmid = {26215258}, issn = {1471-2164}, support = {K08 AI085028/AI/NIAID NIH HHS/United States ; 1K08AI085028/AI/NIAID NIH HHS/United States ; }, mesh = {Bacteriophages/classification/*genetics/physiology ; Gene Expression Profiling/*methods ; Gene Expression Regulation, Viral ; Humans ; Lysogeny ; Mouth/*virology ; Periodontal Diseases/genetics/*virology ; Sequence Analysis, RNA/methods ; Viral Proteins/genetics ; }, abstract = {BACKGROUND: The role of viruses as members of the human microbiome has gained broader attention with the discovery that human body surfaces are inhabited by sizeable viral communities. The majority of the viruses identified in these communities have been bacteriophages that predate upon cellular microbiota rather than the human host. Phages have the capacity to lyse their hosts or provide them with selective advantages through lysogenic conversion, which could help determine the structure of co-existing bacterial communities. Because conditions such as periodontitis are associated with altered bacterial biota, phage mediated perturbations of bacterial communities have been hypothesized to play a role in promoting periodontal disease. Oral phage communities also differ significantly between periodontal health and disease, but the gene expression of oral phage communities has not been previously examined.<br><br>RESULTS: Here, we provide the first report of gene expression profiles from the oral bacteriophage community using RNA sequencing, and find that oral phages are more highly expressed in subjects with relative periodontal health. While lysins were highly expressed, the high proportion of integrases expressed suggests that prophages may account for a considerable proportion of oral phage gene expression. Many of the transcriptome reads matched phages found in the oral cavities of the subjects studied, indicating that phages may account for a substantial proportion of oral gene expression. Reads homologous to siphoviruses that infect Firmicutes were amongst the most prevalent transcriptome reads identified in both periodontal health and disease. Some genes from the phage lytic module were significantly more highly expressed in subjects with periodontal disease, suggesting that periodontitis may favor the expression of some lytic phages.<br><br>CONCLUSIONS: As we explore the contributions of viruses to the human microbiome, the data presented here suggest varying expression of bacteriophage communities in oral health and disease.}, }
@article {pmid26210106, year = {2015}, author = {Rabus, R and Venceslau, SS and Wöhlbrand, L and Voordouw, G and Wall, JD and Pereira, IA}, title = {A Post-Genomic View of the Ecophysiology, Catabolism and Biotechnological Relevance of Sulphate-Reducing Prokaryotes.}, journal = {Advances in microbial physiology}, volume = {66}, number = {}, pages = {55-321}, doi = {10.1016/bs.ampbs.2015.05.002}, pmid = {26210106}, issn = {2162-5468}, mesh = {Bioelectric Energy Sources ; Biotechnology/*methods/trends ; Corrosion ; Environmental Restoration and Remediation/methods ; *Genome, Microbial ; Metabolic Networks and Pathways/*genetics ; Metabolism ; Oxidation-Reduction ; Prokaryotic Cells/*metabolism ; Sulfates/*metabolism ; Water Purification/methods ; }, abstract = {Dissimilatory sulphate reduction is the unifying and defining trait of sulphate-reducing prokaryotes (SRP). In their predominant habitats, sulphate-rich marine sediments, SRP have long been recognized to be major players in the carbon and sulphur cycles. Other, more recently appreciated, ecophysiological roles include activity in the deep biosphere, symbiotic relations, syntrophic associations, human microbiome/health and long-distance electron transfer. SRP include a high diversity of organisms, with large nutritional versatility and broad metabolic capacities, including anaerobic degradation of aromatic compounds and hydrocarbons. Elucidation of novel catabolic capacities as well as progress in the understanding of metabolic and regulatory networks, energy metabolism, evolutionary processes and adaptation to changing environmental conditions has greatly benefited from genomics, functional OMICS approaches and advances in genetic accessibility and biochemical studies. Important biotechnological roles of SRP range from (i) wastewater and off gas treatment, (ii) bioremediation of metals and hydrocarbons and (iii) bioelectrochemistry, to undesired impacts such as (iv) souring in oil reservoirs and other environments, and (v) corrosion of iron and concrete. Here we review recent advances in our understanding of SRPs focusing mainly on works published after 2000. The wealth of publications in this period, covering many diverse areas, is a testimony to the large environmental, biogeochemical and technological relevance of these organisms and how much the field has progressed in these years, although many important questions and applications remain to be explored.}, }
@article {pmid26207044, year = {2015}, author = {Cameron, SJ and Huws, SA and Hegarty, MJ and Smith, DP and Mur, LA}, title = {The human salivary microbiome exhibits temporal stability in bacterial diversity.}, journal = {FEMS microbiology ecology}, volume = {91}, number = {9}, pages = {fiv091}, doi = {10.1093/femsec/fiv091}, pmid = {26207044}, issn = {1574-6941}, mesh = {Actinobacteria/genetics/physiology ; Adult ; Bacteroidetes/genetics/physiology ; Base Sequence ; Biodiversity ; DNA, Bacterial/genetics ; Female ; Fusobacteria/genetics/physiology ; Gene Dosage/*genetics ; Humans ; Male ; Metagenome/genetics ; Microbiota/genetics/*physiology ; Proteobacteria/genetics/physiology ; RNA, Ribosomal, 16S/genetics ; Saliva/*microbiology ; Sequence Analysis, DNA ; }, abstract = {The temporal variability of the human microbiome may be an important factor in determining its relationship with health and disease. In this study, the saliva of 40 participants was collected every 2 months over a one-year period to determine the temporal variability of the human salivary microbiome. Salivary pH and 16S rRNA gene copy number were measured for all participants, with the microbiome of 10 participants assessed through 16S rRNA amplicon sequencing. In February 2013, 16S rRNA gene copy number was significantly (P < 0.001) higher, with individual changes between time points significant (P = 0.003). Salivary pH levels were significantly (P < 0.001) higher in December 2012 than in October 2012 and February 2013, with significant (P < 0.001) individual variations seen throughout. Bacterial α-diversity showed significant differences between participants (P < 0.001), but not sampling periods (P = 0.801), and a significant positive correlation with salivary pH (R(2) = 7.8%; P = 0.019). At the phylum level, significant differences were evident between participants in the Actinobacteria (P < 0.001), Bacteroidetes (P < 0.001), Firmicutes (P = 0.008), Fusobacteria (P < 0.001), Proteobacteria (P < 0.001), Synergistetes (P < 0.001) and Spirochaetes (P = 0.003) phyla. This study charted the temporal variability of the salivary microbiome, suggesting that bacterial diversity is stable, but that 16S rRNA gene copy number may be subject to seasonal flux.}, }
@article {pmid26206939, year = {2015}, author = {Donia, MS and Fischbach, MA}, title = {HUMAN MICROBIOTA. Small molecules from the human microbiota.}, journal = {Science (New York, N.Y.)}, volume = {349}, number = {6246}, pages = {1254766}, pmid = {26206939}, issn = {1095-9203}, support = {R01 AI101018/AI/NIAID NIH HHS/United States ; DP2 OD007290/OD/NIH HHS/United States ; R01 DK101674/DK/NIDDK NIH HHS/United States ; GM081879/GM/NIGMS NIH HHS/United States ; AI101018/AI/NIAID NIH HHS/United States ; DK101674/DK/NIDDK NIH HHS/United States ; P50 GM081879/GM/NIGMS NIH HHS/United States ; OD007290/OD/NIH HHS/United States ; }, mesh = {Antibiosis ; Bacteriocins/isolation &amp; purification/metabolism/pharmacology ; *Biological Products/isolation &amp; purification/metabolism/pharmacology ; Enterotoxins/isolation &amp; purification/metabolism/pharmacology ; Glycolipids/isolation &amp; purification/metabolism/pharmacology ; Humans ; Immunomodulation ; *Microbiota ; Oligosaccharides/isolation &amp; purification/metabolism/pharmacology ; Peptides/isolation &amp; purification/metabolism/pharmacology ; Protein Processing, Post-Translational ; Ribosomes/metabolism ; Terpenes/isolation &amp; purification/metabolism/pharmacology ; }, abstract = {Developments in the use of genomics to guide natural product discovery and a recent emphasis on understanding the molecular mechanisms of microbiota-host interactions have converged on the discovery of small molecules from the human microbiome. Here, we review what is known about small molecules produced by the human microbiota. Numerous molecules representing each of the major metabolite classes have been found that have a variety of biological activities, including immune modulation and antibiosis. We discuss technologies that will affect how microbiota-derived molecules are discovered in the future and consider the challenges inherent in finding specific molecules that are critical for driving microbe-host and microbe-microbe interactions and understanding their biological relevance.}, }
@article {pmid26203331, year = {2015}, author = {Mukherjee, S and Huntemann, M and Ivanova, N and Kyrpides, NC and Pati, A}, title = {Large-scale contamination of microbial isolate genomes by Illumina PhiX control.}, journal = {Standards in genomic sciences}, volume = {10}, number = {}, pages = {18}, pmid = {26203331}, issn = {1944-3277}, abstract = {With the rapid growth and development of sequencing technologies, genomes have become the new go-to for exploring solutions to some of the world's biggest challenges such as searching for alternative energy sources and exploration of genomic dark matter. However, progress in sequencing has been accompanied by its share of errors that can occur during template or library preparation, sequencing, imaging or data analysis. In this study we screened over 18,000 publicly available microbial isolate genome sequences in the Integrated Microbial Genomes database and identified more than 1000 genomes that are contaminated with PhiX, a control frequently used during Illumina sequencing runs. Approximately 10% of these genomes have been published in literature and 129 contaminated genomes were sequenced under the Human Microbiome Project. Raw sequence reads are prone to contamination from various sources and are usually eliminated during downstream quality control steps. Detection of PhiX contaminated genomes indicates a lapse in either the application or effectiveness of proper quality control measures. The presence of PhiX contamination in several publicly available isolate genomes can result in additional errors when such data are used in comparative genomics analyses. Such contamination of public databases have far-reaching consequences in the form of erroneous data interpretation and analyses, and necessitates better measures to proofread raw sequences before releasing them to the broader scientific community.}, }
@article {pmid26202196, year = {2015}, author = {Ajami, NJ and Hutchinson, DS and Petrosino, JF}, title = {Promise and Pragmatism in Clinical Microbiome Research.}, journal = {Mini reviews in medicinal chemistry}, volume = {16}, number = {3}, pages = {222-224}, doi = {10.2174/1389557515666150722103457}, pmid = {26202196}, issn = {1875-5607}, mesh = {High-Throughput Nucleotide Sequencing/trends ; Humans ; *Microbiota ; Research/*trends ; }, abstract = {The evolution of human microbiome research has lead to a systems biology approach that encompasses multidisciplinary investigations. The implementation of next generation sequencing technologies has allowed researchers to study unculturable organisms, discover novel ones, and provide insights into the role of the human microbiome in health and disease. When these approaches are applied to large-scale longitudinal studies designed to interrogate the association of the microbiome with specific clinical outcomes, the development of new therapeutics and diagnostics intended to modulate or detect changes in microbiome composition to improve human health are born. We are just starting to unravel the role of the microbiome in a wide-variety of diseases, and while some of it appears to be related to causation and provide opportunities for intervention, a good dose of pragmatism is warranted as the field is still in its infancy.}, }
@article {pmid26199462, year = {2015}, author = {Murray, MA and Chotirmall, SH}, title = {The Impact of Immunosenescence on Pulmonary Disease.}, journal = {Mediators of inflammation}, volume = {2015}, number = {}, pages = {692546}, pmid = {26199462}, issn = {1466-1861}, mesh = {Aging/immunology/physiology ; Disease Susceptibility ; Humans ; Immunosenescence/*immunology ; Lung Diseases/*immunology ; Microbiota ; }, abstract = {The global population is aging with significant gains in life expectancy particularly in the developed world. Consequently, greater focus on understanding the processes that underlie physiological aging has occurred. Key facets of advancing age include genomic instability, telomere shortening, epigenetic changes, and declines in immune function termed immunosenescence. Immunosenescence and its associated chronic low grade systemic "inflamm-aging" contribute to the development and progression of pulmonary disease in older individuals. These physiological processes predispose to pulmonary infection and confer specific and unique clinical phenotypes observed in chronic respiratory disease including late-onset asthma, chronic obstructive pulmonary disease, and pulmonary fibrosis. Emerging concepts of the gut and airway microbiome further complicate the interrelationship between host and microorganism particularly from an immunological perspective and especially so in the setting of immunosenescence. This review focuses on our current understanding of the aging process, immunosenescence, and how it can potentially impact on various pulmonary diseases and the human microbiome.}, }
@article {pmid26198938, year = {2015}, author = {Sheng, HF and Zhou, HW}, title = {[Methods, challenges and opportunities for big data analyses of microbiome].}, journal = {Nan fang yi ke da xue xue bao = Journal of Southern Medical University}, volume = {35}, number = {7}, pages = {931-934}, pmid = {26198938}, issn = {1673-4254}, mesh = {Bacteria/classification ; Humans ; *Metagenome ; *Microbiota ; RNA, Ribosomal, 16S ; }, abstract = {Microbiome is a novel research field related with a variety of chronic inflamatory diseases. Technically, there are two major approaches to analysis of microbiome: metataxonome by sequencing the 16S rRNA variable tags, and metagenome by shot-gun sequencing of the total microbial (mainly bacterial) genome mixture. The 16S rRNA sequencing analyses pipeline includes sequence quality control, diversity analyses, taxonomy and statistics; metagenome analyses further includes gene annotation and functional analyses. With the development of the sequencing techniques, the cost of sequencing will decrease, and big data analyses will become the central task. Data standardization, accumulation, modeling and disease prediction are crucial for future exploit of these data. Meanwhile, the information property in these data, and the functional verification with culture-dependent and culture-independent experiments remain the focus in future research. Studies of human microbiome will bring a better understanding of the relations between the human body and the microbiome, especially in the context of disease diagnosis and therapy, which promise rich research opportunities.}, }
@article {pmid26198391, year = {2015}, author = {Marchesan, JT and Morelli, T and Moss, K and Barros, SP and Ward, M and Jenkins, W and Aspiras, MB and Offenbacher, S}, title = {Association of Synergistetes and Cyclodipeptides with Periodontitis.}, journal = {Journal of dental research}, volume = {94}, number = {10}, pages = {1425-1431}, doi = {10.1177/0022034515594779}, pmid = {26198391}, issn = {1544-0591}, mesh = {Biofilms ; Dental Plaque/microbiology ; Dipeptides/*analysis ; Gas Chromatography-Mass Spectrometry ; *Gram-Negative Anaerobic Bacteria ; Gram-Negative Bacterial Infections/*complications/microbiology ; Humans ; Metabolome ; Peptides, Cyclic/*analysis ; Periodontitis/etiology/*microbiology ; Saliva/chemistry/microbiology ; Spirochaetales ; }, abstract = {The purpose of this study was to evaluate the microbial community (MC) composition as it relates to salivary metabolites and periodontal clinical parameters in a 21-d biofilm-overgrowth model. Subjects (N = 168) were enrolled equally into 5 categories of periodontal status per the biofilm-gingival interface classification. Microbial species within subgingival plaque samples were identified by human microbiome identification microarray. Whole saliva was analyzed by liquid chromatography-mass spectrometry and gas chromatography-mass spectrometry for metabolite identification. Phylum was grouped into MCs according to principal component analysis. Generalized linear and regression models were used to examine the association among MC, species, periodontal clinical parameters, and salivary metabolome. Multiple comparisons were adjusted with the false discovery rate. The study population was distributed into 8 distinct MC profiles, designated MC-1 to MC-8. MC-2 explained 14% of the variance and was dominated by Synergistetes and Spirochaetes. It was the only community structure significantly associated with high probing depth (P = 0.02) and high bleeding on probing (P = 0.008). MC-2 was correlated with traditional periodontal pathogens and several newly identified putative periodontal pathogens: Fretibacterium fastidiosum, Fretibacterium sp. OT360/OT362, Filifactor alocis, Treponema lecithinolyticum, Eubacterium saphenum, Desulfobulbus sp./OT041, and Mogibacterium timidum. Synergistetes phylum was strongly associated with 2 novel metabolites-cyclo (-leu-pro) and cyclo (-phe-pro)-at 21 d of biofilm overgrowth (P = 0.02). In subjects with severe periodontitis (P2 and P3), cyclo (-leu-pro) and cyclo (-phe-pro) were significantly associated with increased changes in probing depth at 21 d of biofilm overgrowth (P ≤ 0.05). The analysis identified a MC dominated by Synergistetes, with classic and putative newly identified pathogens/pathobionts associated with clinical disease. The metabolomic discovery of 2 novel cyclodipeptides that have been reported to serve as quorum-sensing and/or bacteriocidal/bacteriostatic molecules, in association with Synergistetes, suggests a potential role in periodontal biofilm dysbiosis and periodontal disease that warrants further investigation.}, }
@article {pmid26198190, year = {2015}, author = {Smith, VH and Rubinstein, RJ and Park, S and Kelly, L and Klepac-Ceraj, V}, title = {Microbiology and ecology are vitally important to premedical curricula.}, journal = {Evolution, medicine, and public health}, volume = {2015}, number = {1}, pages = {179-192}, pmid = {26198190}, issn = {2050-6201}, abstract = {Despite the impact of the human microbiome on health, an appreciation of microbial ecology is yet to be translated into mainstream medical training and practice. The human microbiota plays a role in the development of the immune system, in the development and function of the brain, in digestion, and in host defense, and we anticipate that many more functions are yet to be discovered. We argue here that without formal exposure to microbiology and ecology-fields that explore the networks, interactions and dynamics between members of populations of microbes-vitally important links between the human microbiome and health will be overlooked. This educational shortfall has significant downstream effects on patient care and biomedical research, and we provide examples from current research highlighting the influence of the microbiome on human health. We conclude that formally incorporating microbiology and ecology into the premedical curricula is invaluable to the training of future health professionals and critical to the development of novel therapeutics and treatment practices.}, }
@article {pmid26185089, year = {2015}, author = {Wolfe, AJ}, title = {Glycolysis for Microbiome Generation.}, journal = {Microbiology spectrum}, volume = {3}, number = {3}, pages = {}, pmid = {26185089}, issn = {2165-0497}, support = {R01 AI108255/AI/NIAID NIH HHS/United States ; R21 DK097435/DK/NIDDK NIH HHS/United States ; DE-SC0012443/DE/NIDCR NIH HHS/United States ; R01AI108255/AI/NIAID NIH HHS/United States ; }, mesh = {Bacteria/*metabolism/pathogenicity ; Fermentation/physiology ; Glycolysis/*physiology ; Host-Pathogen Interactions/*physiology ; Humans ; Microbiota/*physiology ; Pentose Phosphate Pathway/physiology ; }, abstract = {For a generation of microbiologists who study pathogenesis in the context of the human microbiome, understanding the diversity of bacterial metabolism is essential. In this chapter, I briefly describe how and why I became, and remain, interested in metabolism. I then will describe and compare some of the strategies used by bacteria to consume sugars as one example of metabolic diversity. I will end with a plea to embrace metabolism in the endeavor to understand pathogenesis.}, }
@article {pmid26184597, year = {2015}, author = {Soucy, SM and Huang, J and Gogarten, JP}, title = {Horizontal gene transfer: building the web of life.}, journal = {Nature reviews. Genetics}, volume = {16}, number = {8}, pages = {472-482}, pmid = {26184597}, issn = {1471-0064}, mesh = {Eukaryota/*genetics ; *Evolution, Molecular ; Gene Transfer, Horizontal/*genetics/*physiology ; *Models, Genetic ; *Phylogeny ; *Selection, Genetic ; Symbiosis/*genetics ; }, abstract = {Horizontal gene transfer (HGT) is the sharing of genetic material between organisms that are not in a parent-offspring relationship. HGT is a widely recognized mechanism for adaptation in bacteria and archaea. Microbial antibiotic resistance and pathogenicity are often associated with HGT, but the scope of HGT extends far beyond disease-causing organisms. In this Review, we describe how HGT has shaped the web of life using examples of HGT among prokaryotes, between prokaryotes and eukaryotes, and even between multicellular eukaryotes. We discuss replacement and additive HGT, the proposed mechanisms of HGT, selective forces that influence HGT, and the evolutionary impact of HGT on ancestral populations and existing populations such as the human microbiome.}, }
@article {pmid26140087, year = {2015}, author = {Abdul-Hai, A and Abdallah, A and Malnick, SD}, title = {Influence of gut bacteria on development and progression of non-alcoholic fatty liver disease.}, journal = {World journal of hepatology}, volume = {7}, number = {12}, pages = {1679-1684}, pmid = {26140087}, issn = {1948-5182}, abstract = {The intestine of the human contains a dynamic population of microbes that have a symbiotic relationship with the host. In addition, there is an effect of the intestinal microbiota on metabolism and digestion. Non-alcoholic fatty liver disease (NAFLD) is a common cause worldwide of hepatic pathology and is thought to be the hepatic manifestation of the metabolic syndrome. In this review we examine the effect of the human microbiome on the components and pathogenesis of the metabolic syndrome. We are now on the threshold of therapeutic interventions on the human microbiome in order to effect human disease including NAFLD.}, }
@article {pmid26137199, year = {2015}, author = {Bikel, S and Valdez-Lara, A and Cornejo-Granados, F and Rico, K and Canizales-Quinteros, S and Soberón, X and Del Pozo-Yauner, L and Ochoa-Leyva, A}, title = {Combining metagenomics, metatranscriptomics and viromics to explore novel microbial interactions: towards a systems-level understanding of human microbiome.}, journal = {Computational and structural biotechnology journal}, volume = {13}, number = {}, pages = {390-401}, pmid = {26137199}, issn = {2001-0370}, abstract = {The advances in experimental methods and the development of high performance bioinformatic tools have substantially improved our understanding of microbial communities associated with human niches. Many studies have documented that changes in microbial abundance and composition of the human microbiome is associated with human health and diseased state. The majority of research on human microbiome is typically focused in the analysis of one level of biological information, i.e., metagenomics or metatranscriptomics. In this review, we describe some of the different experimental and bioinformatic strategies applied to analyze the 16S rRNA gene profiling and shotgun sequencing data of the human microbiome. We also discuss how some of the recent insights in the combination of metagenomics, metatranscriptomics and viromics can provide more detailed description on the interactions between microorganisms and viruses in oral and gut microbiomes. Recent studies on viromics have begun to gain importance due to the potential involvement of viruses in microbial dysbiosis. In addition, metatranscriptomic combined with metagenomic analysis have shown that a substantial fraction of microbial transcripts can be differentially regulated relative to their microbial genomic abundances. Thus, understanding the molecular interactions in the microbiome using the combination of metagenomics, metatranscriptomics and viromics is one of the main challenges towards a system level understanding of human microbiome.}, }
@article {pmid26134992, year = {2015}, author = {Simón-Soro, &#xc1; and D'Auria, G and Collado, MC and Džunková, M and Culshaw, S and Mira, A}, title = {Revealing microbial recognition by specific antibodies.}, journal = {BMC microbiology}, volume = {15}, number = {}, pages = {132}, pmid = {26134992}, issn = {1471-2180}, mesh = {Antibodies, Bacterial/*analysis/*blood ; Bacteria/classification/*immunology/isolation &amp; purification ; Feces/microbiology ; Female ; Humans ; *Microbiota ; Milk, Human/microbiology ; Mouth Mucosa/microbiology ; Saliva/microbiology ; }, abstract = {BACKGROUND: Recognition of microorganisms by antibodies is a vital component of the human immune response. However, there is currently very limited understanding of immune recognition of 50 % of the human microbiome which is made up of as yet un-culturable bacteria. We have combined the use of flow cytometry and pyrosequencing to describe the microbial composition of human samples, and its interaction with the immune system.<br><br>RESULTS: We show the power of the technique in human faecal, saliva, oral biofilm and breast milk samples, labeled with fluorescent anti-IgG or anti-IgA antibodies. Using Fluorescence-Activated Cell Sorting (FACS), bacterial cells were separated depending on whether they are coated with IgA or IgG antibodies. Each bacterial population was PCR-amplified and pyrosequenced, characterizing the microorganisms which evade the immune system and those which were recognized by each immunoglobulin.<br><br>CONCLUSIONS: The application of the technique to healthy and diseased individuals may unravel the contribution of the immune response to microbial infections and polymicrobial diseases.}, }
@article {pmid26130323, year = {2016}, author = {Bashir, M and Prietl, B and Tauschmann, M and Mautner, SI and Kump, PK and Treiber, G and Wurm, P and Gorkiewicz, G and Högenauer, C and Pieber, TR}, title = {Effects of high doses of vitamin D3 on mucosa-associated gut microbiome vary between regions of the human gastrointestinal tract.}, journal = {European journal of nutrition}, volume = {55}, number = {4}, pages = {1479-1489}, pmid = {26130323}, issn = {1436-6215}, mesh = {Adolescent ; Adult ; CD8-Positive T-Lymphocytes/cytology ; Cholecalciferol/*pharmacology ; Feces/microbiology ; Female ; Gammaproteobacteria/drug effects/isolation &amp; purification ; Gastrointestinal Microbiome/*drug effects ; Gastrointestinal Tract/*microbiology ; Helicobacter pylori/drug effects ; Humans ; Male ; Mucous Membrane/*microbiology ; Pilot Projects ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; Young Adult ; }, abstract = {PURPOSE: Vitamin D is well known for its effects on bone mineralisation but has also been attributed immunomodulatory properties. It positively influences human health, but in vivo data describing vitamin D effects on the human gut microbiome are missing. We aimed to investigate the effects of oral vitamin D3 supplementation on the human mucosa-associated and stool microbiome as well as CD8(+) T cells in healthy volunteers.<br><br>METHODS: This was an interventional, open-label, pilot study. Sixteen healthy volunteers (7 females, 9 males) were endoscopically examined to access a total of 7 sites. We sampled stomach, small bowel, colon, and stools before and after 8&#xa0;weeks of vitamin D3 supplementation. Bacterial composition was assessed by pyrosequencing the 16S rRNA gene (V1-2), and CD8(+) T cell counts were determined by flow cytometry.<br><br>RESULTS: Vitamin D3 supplementation changed the gut microbiome in the upper GI tract (gastric corpus, antrum, and duodenum). We found a decreased relative abundance of Gammaproteobacteria including Pseudomonas spp. and Escherichia/Shigella spp. and increased bacterial richness. No major changes occurred in the terminal ileum, appendiceal orifice, ascending colon, and sigmoid colon or in stools, but the CD8(+) T cell fraction was significantly increased in the terminal ileum.<br><br>CONCLUSION: Vitamin D3 modulates the gut microbiome of the upper GI tract which might explain its positive influence on gastrointestinal diseases, such as inflammatory bowel disease or bacterial infections. The local effects of vitamin D demonstrate pronounced regional differences in the response of the GI microbiome to external factors, which should be considered in future studies investigating the human microbiome.}, }
@article {pmid26123785, year = {2015}, author = {Trinder, M and Bisanz, JE and Burton, JP and Reid, G}, title = {Probiotic lactobacilli: a potential prophylactic treatment for reducing pesticide absorption in humans and wildlife.}, journal = {Beneficial microbes}, volume = {6}, number = {6}, pages = {841-847}, doi = {10.3920/BM2015.0022}, pmid = {26123785}, issn = {1876-2891}, mesh = {Animals ; Biotransformation ; Humans ; Lacticaseibacillus rhamnosus/*growth &amp; development/*metabolism ; Pesticides/*antagonists &amp; inhibitors/*metabolism ; Probiotics/*administration &amp; dosage ; }, abstract = {Numerous pesticides are used in agriculture, gardening, and wildlife-control. Despite their intended toxicity to pests, these compounds can also cause harm to wildlife and humans due to their ability to potentially bioaccumulate, leach into soils, and persist in the environment. Humans and animals are commonly exposed to these compounds through agricultural practices and consumption of contaminated foods and water. Pesticides can cause a range of adverse effects in humans ranging from minor irritation, to endocrine or nervous system disruption, cancer, or even death. A convenient and cost-effective method to reduce unavoidable pesticide absorption in humans and wildlife could be the use of probiotic lactobacilli. Lactobacillus is a genus of Gram-positive gut commensal bacteria used in the production of functional foods, such as yoghurt, cheese, sauerkraut and pickles, as well as silage for animal feed. Preliminary in vitro experiments suggested that lactobacilli are able to degrade some pesticides. Probiotic Lactobacillus rhamnosus GR-1-supplemented yoghurt reduced the bioaccumulation of mercury and arsenic in pregnant women and children. A similar study is warranted to test if this approach can reduce pesticide absorption in vivo, given that the lactobacilli can also attenuate reactive oxygen production, enhance gastrointestinal barrier function, reduce inflammation, and modulate host xenobiotic metabolism.}, }
@article {pmid26121551, year = {2015}, author = {Sato, Y and Yamagishi, J and Yamashita, R and Shinozaki, N and Ye, B and Yamada, T and Yamamoto, M and Nagasaki, M and Tsuboi, A}, title = {Inter-Individual Differences in the Oral Bacteriome Are Greater than Intra-Day Fluctuations in Individuals.}, journal = {PloS one}, volume = {10}, number = {6}, pages = {e0131607}, pmid = {26121551}, issn = {1932-6203}, mesh = {Adult ; Bacteria/*classification/*genetics ; Biodiversity ; Cluster Analysis ; DNA Barcoding, Taxonomic ; Dental Plaque/microbiology ; Humans ; Male ; *Metagenome ; *Microbiota ; Mouth/*microbiology ; Phylogeny ; RNA, Ribosomal, 16S/genetics ; Time Factors ; }, abstract = {Given the advent of massively parallel DNA sequencing, human microbiome is analyzed comprehensively by metagenomic approaches. However, the inter- and intra-individual variability and stability of the human microbiome remain poorly characterized, particularly at the intra-day level. This issue is of crucial importance for studies examining the effects of microbiome on human health. Here, we focused on bacteriome of oral plaques, for which repeated, time-controlled sampling is feasible. Eighty-one supragingival plaque subjects were collected from healthy individuals, examining multiple sites within the mouth at three time points (forenoon, evening, and night) over the course of 3 days. Bacterial composition was estimated by 16S rRNA sequencing and species-level profiling, resulting in identification of a total of 162 known bacterial species. We found that species compositions and their relative abundances were similar within individuals, and not between sampling time or tooth type. This suggests that species-level oral bacterial composition differs significantly between individuals, although the number of subjects is limited and the intra-individual variation also occurs. The majority of detected bacterial species (98.2%; 159/162), however, did not fluctuate over the course of the day, implying a largely stable oral microbiome on an intra-day time scale. In fact, the stability of this data set enabled us to estimate potential interactions between rare bacteria, with 40 co-occurrences supported by the existing literature. In summary, the present study provides a valuable basis for studies of the human microbiome, with significant implications in terms of biological and clinical outcomes.}, }
@article {pmid26113975, year = {2015}, author = {Wood, M and Gibbons, SM and Lax, S and Eshoo-Anton, TW and Owens, SM and Kennedy, S and Gilbert, JA and Hampton-Marcell, JT}, title = {Athletic equipment microbiota are shaped by interactions with human skin.}, journal = {Microbiome}, volume = {3}, number = {}, pages = {25}, pmid = {26113975}, issn = {2049-2618}, support = {T32 EB009412/EB/NIBIB NIH HHS/United States ; }, abstract = {BACKGROUND: Americans spend the vast majority of their lives in built environments. Even traditionally outdoor pursuits, such as exercising, are often now performed indoors. Bacteria that colonize these indoor ecosystems are primarily derived from the human microbiome. The modes of human interaction with indoor surfaces and the physical conditions associated with each surface type determine the steady-state ecology of the microbial community.<br><br>RESULTS: Bacterial assemblages associated with different surfaces in three athletic facilities, including floors, mats, benches, free weights, and elliptical handles, were sampled every other hour (8&#xa0;am to 6&#xa0;pm) for 2&#xa0;days. Surface and equipment type had a stronger influence on bacterial community composition than the facility in which they were housed. Surfaces that were primarily in contact with human skin exhibited highly dynamic bacterial community composition and non-random co-occurrence patterns, suggesting that different host microbiomes-shaped by selective forces-were being deposited on these surfaces through time. However, bacterial assemblages found on the floors and mats changed less over time, and species co-occurrence patterns appeared random, suggesting more neutral community assembly.<br><br>CONCLUSIONS: These longitudinal patterns highlight the dramatic turnover of microbial communities on surfaces in regular contact with human skin. By uncovering these longitudinal patterns, this study promotes a better understanding of microbe-human interactions within the built environment.}, }
@article {pmid26110290, year = {2015}, author = {De Rosa, FG and Corcione, S and Raviolo, S and Montrucchio, C and Aldieri, C and Pagani, N and Di Perri, G}, title = {Candidemia, and infections by Clostridium difficile and carbapenemase-producing Enterobacteriaceae: new enteropathogenetic opportunistic syndromes?.}, journal = {Le infezioni in medicina}, volume = {23}, number = {2}, pages = {105-116}, pmid = {26110290}, issn = {2532-8689}, mesh = {Anti-Bacterial Agents/pharmacology/therapeutic use ; Bacterial Proteins/*biosynthesis/metabolism ; Candidemia/*complications/diagnosis/epidemiology ; *Clostridioides difficile/enzymology/genetics/isolation &amp; purification ; Clostridium Infections/*complications/diagnosis/epidemiology ; Cross Infection/*prevention &amp; control ; Enterobacteriaceae Infections/*complications/diagnosis/epidemiology ; Humans ; Incidence ; Italy/epidemiology ; Opportunistic Infections/*complications/diagnosis/epidemiology ; Syndrome ; beta-Lactamases/*biosynthesis/metabolism ; }, abstract = {In this paper we analyze three enteropathogenetic opportunistic infections represented by Candida spp., C. difficile and carbapenemase-producing K. pneumoniae. The common pathogenetic pathway is based on an alteration of the intestinal flora, now mainly referred as the human microbiome, with secondary opportunism for infections caused by Candida, C. difficile and carbapenemase-producing Enterobacteriaceae ("CCC"). We highlight the epidemiology, risk factors, clinical syndromes associated with the pathogens and we propose some new issues related to the epidemiology and diagnosis of candidemia, also using hierarchical cluster analysis, definitions of levels of interventions in patients colonized or infected by carbapenemase-producing bacteria. The "enteropathogenetic" opportunistic syndromes are best prevented with antimicrobial stewardship programs aiming at increasing diagnostic specificity of infectious syndromes to reduce the antimicrobial use and costs. Appropriate guidelines for infection control should also be implemented to reduce the nosocomial spread of enteropathogenetic microbes.}, }
@article {pmid26097896, year = {2015}, author = {Zhao, Y and Lukiw, WJ}, title = {Microbiome-generated amyloid and potential impact on amyloidogenesis in Alzheimer's disease (AD).}, journal = {Journal of nature and science}, volume = {1}, number = {7}, pages = {}, pmid = {26097896}, issn = {2377-2700}, support = {R01 AG018031/AG/NIA NIH HHS/United States ; R01 AG038834/AG/NIA NIH HHS/United States ; R01 EY006311/EY/NEI NIH HHS/United States ; }, abstract = {According to the 'amyloid cascade hypothesis of Alzheimer's disease' first proposed about 16 years ago, the accumulation of Aβ peptides in the human central nervous system (CNS) is the primary influence driving Alzheimer's disease (AD) pathogenesis, and Aβ peptide accretion is the result of an imbalance between Aβ peptide production and clearance. In the last 18 months multiple laboratories have reported two particularly important observations: (i) that because the microbes of the human microbiome naturally secrete large amounts of amyloid, lipopolysaccharides (LPS) and other related pro-inflammatory pathogenic signals, these may contribute to both the systemic and CNS amyloid burden in aging humans; and (ii) that the clearance of Aβ peptides appears to be intrinsically impaired by deficits in the microglial plasma-membrane enriched triggering receptor expressed in microglial/myeloid-2 cells (TREM2). This brief general commentary-perspective paper: (i) will highlight some of these very recent findings on microbiome-secreted amyloids and LPS and the potential contribution of these microbial-derived pro-inflammatory and neurotoxic exudates to age-related inflammatory and AD-type neurodegeneration in the host; and (ii) will discuss the contribution of a defective microglial-based TREM2 transmembrane sensor-receptor system to amyloidogenesis in AD that is in contrast to the normal, homeostatic clearance of Aβ peptides from the human CNS.}, }
@article {pmid26096156, year = {2015}, author = {Hauther, KA and Cobaugh, KL and Jantz, LM and Sparer, TE and DeBruyn, JM}, title = {Estimating Time Since Death from Postmortem Human Gut Microbial Communities.}, journal = {Journal of forensic sciences}, volume = {60}, number = {5}, pages = {1234-1240}, doi = {10.1111/1556-4029.12828}, pmid = {26096156}, issn = {1556-4029}, mesh = {Aged ; Aged, 80 and over ; Bacteroides/genetics/physiology ; Bifidobacterium/genetics/physiology ; Female ; Gastrointestinal Microbiome ; Humans ; Intestines/*microbiology ; Lactobacillus/genetics/physiology ; Male ; Middle Aged ; Polymerase Chain Reaction ; *Postmortem Changes ; RNA, Ribosomal, 16S/metabolism ; }, abstract = {Postmortem succession of human-associated microbial communities ("human microbiome") has been suggested as a possible method for estimating postmortem interval (PMI) for forensic analyses. Here we evaluate human gut bacterial populations to determine quantifiable, time-dependent changes postmortem. Gut microflora were repeatedly sampled from the proximal large intestine of 12 deceased human individuals as they decayed under environmental conditions. Three intestinal bacterial genera were quantified by quantitative PCR (qPCR) using group-specific primers targeting 16S rRNA genes. Bacteroides and Lactobacillus relative abundances declined exponentially with increasing PMI at rates of Nt=0.977e(-0.0144t) (r2=0.537, p<0.001) and Nt=0.019e(-0.0087t) (r2=0.396, p<0.001), respectively, where Nt is relative abundance at time (t) in cumulative degree hours. Bifidobacterium relative abundances did not change significantly: Nt=0.003e(-0.002t) (r2=0.033, p=0.284). Therefore, Bacteroides and Lactobacillus abundances could be used as quantitative indicators of PMI.}, }
@article {pmid26084027, year = {2015}, author = {Gallo, PM and Rapsinski, GJ and Wilson, RP and Oppong, GO and Sriram, U and Goulian, M and Buttaro, B and Caricchio, R and Gallucci, S and Tükel, &#xc7;}, title = {Amyloid-DNA Composites of Bacterial Biofilms Stimulate Autoimmunity.}, journal = {Immunity}, volume = {42}, number = {6}, pages = {1171-1184}, pmid = {26084027}, issn = {1097-4180}, support = {R01-AI076423/AI/NIAID NIH HHS/United States ; 1R21AI105370/AI/NIAID NIH HHS/United States ; R01 AR061569/AR/NIAMS NIH HHS/United States ; R21 AI105370/AI/NIAID NIH HHS/United States ; R01-AR061569/AR/NIAMS NIH HHS/United States ; 1R03AI107434/AI/NIAID NIH HHS/United States ; R01 GM080279/GM/NIGMS NIH HHS/United States ; R03 AI107434/AI/NIAID NIH HHS/United States ; R01 AI076423/AI/NIAID NIH HHS/United States ; }, mesh = {Amyloid/immunology/*metabolism ; Animals ; Autoantibodies/biosynthesis ; Bacterial Proteins/immunology/*metabolism ; Biofilms/growth &amp; development ; Cells, Cultured ; DNA, Bacterial/immunology/*metabolism ; Dendritic Cells/*immunology ; Escherichia coli/*immunology ; Escherichia coli Infections/*immunology ; Humans ; Interferon Type I/metabolism ; Lupus Erythematosus, Systemic/*immunology ; Mice ; Mice, 129 Strain ; Mice, Inbred C57BL ; Mice, Inbred NZB ; Polymerization ; Salmonella Infections/*immunology ; Salmonella typhimurium/*immunology ; }, abstract = {Research on the human microbiome has established that commensal and pathogenic bacteria can influence obesity, cancer, and autoimmunity through mechanisms mostly unknown. We found that a component of bacterial biofilms, the amyloid protein curli, irreversibly formed fibers with bacterial DNA during biofilm formation. This interaction accelerated amyloid polymerization and created potent immunogenic complexes that activated immune cells, including dendritic cells, to produce cytokines such as type I interferons, which are pathogenic in systemic lupus erythematosus (SLE). When given systemically, curli-DNA composites triggered immune activation and production of autoantibodies in lupus-prone and wild-type mice. We also found that the infection of lupus-prone mice with curli-producing bacteria triggered higher autoantibody titers compared to curli-deficient bacteria. These data provide a mechanism by which the microbiome and biofilm-producing enteric infections may contribute to the progression of SLE and point to a potential molecular target for treatment of autoimmunity.}, }
@article {pmid26074882, year = {2015}, author = {Santiago-Rodriguez, TM and Naidu, M and Jones, MB and Ly, M and Pride, DT}, title = {Identification of staphylococcal phage with reduced transcription in human blood through transcriptome sequencing.}, journal = {Frontiers in microbiology}, volume = {6}, number = {}, pages = {216}, pmid = {26074882}, issn = {1664-302X}, abstract = {Many pathogenic bacteria have bacteriophage and other mobile genetic elements whose activity during human infections has not been evaluated. We investigated the gene expression patterns in human subjects with invasive Methicillin Resistant Staphylococcus aureus (MRSA) infections to determine the gene expression of bacteriophage and other mobile genetic elements. We developed an ex vivo technique that involved direct inoculation of blood from subjects with invasive bloodstream infections into culture media to reduce any potential laboratory adaptation. We compared ex vivo to in vitro profiles from 10 human subjects to determine MRSA gene expression in blood. Using RNA sequencing, we found that there were distinct and significant differences between ex vivo and in vitro MRSA gene expression profiles. Among the major differences between ex vivo and in vitro gene expression were virulence/disease/defense and mobile elements. While transposons were expressed at higher levels ex vivo, lysogenic bacteriophage had significantly higher in vitro expression. Five subjects had MRSA with bacteriophage that were inhibited by the presence of blood in the media, supporting that the lysogeny state was preferred in human blood. Some of the phage produced also had reduced infectivity, further supporting that phage were inhibited by blood. By comparing the gene expression cultured in media with and without the blood of patients, we gain insights into the specific adaptations made by MRSA and its bacteriophage to life in the human bloodstream.}, }
@article {pmid26056565, year = {2015}, author = {Lam, KN and Charles, TC}, title = {Strong spurious transcription likely contributes to DNA insert bias in typical metagenomic clone libraries.}, journal = {Microbiome}, volume = {3}, number = {}, pages = {22}, pmid = {26056565}, issn = {2049-2618}, abstract = {BACKGROUND: Clone libraries provide researchers with a powerful resource to study nucleic acid from diverse sources. Metagenomic clone libraries in particular have aided in studies of microbial biodiversity and function, and allowed the mining of novel enzymes. Libraries are often constructed by cloning large inserts into cosmid or fosmid vectors. Recently, there have been reports of GC bias in fosmid metagenomic libraries, and it was speculated to be a result of fragmentation and loss of AT-rich sequences during cloning. However, evidence in the literature suggests that transcriptional activity or gene product toxicity may play a role.<br><br>RESULTS: To explore possible mechanisms responsible for sequence bias in clone libraries, we constructed a cosmid library from a human microbiome sample and sequenced DNA from different steps during library construction: crude extract DNA, size-selected DNA, and cosmid library DNA. We confirmed a GC bias in the final cosmid library, and we provide evidence that the bias is not due to fragmentation and loss of AT-rich sequences but is likely occurring after DNA is introduced into Escherichia coli. To investigate the influence of strong constitutive transcription, we searched the sequence data for promoters and found that rpoD/&#x3c3;(70) promoter sequences were underrepresented in the cosmid library. Furthermore, when we examined the genomes of taxa that were differentially abundant in the cosmid library relative to the original sample, we found the bias to be more correlated with the number of rpoD/&#x3c3;(70) consensus sequences in the genome than with simple GC content.<br><br>CONCLUSIONS: The GC bias of metagenomic libraries does not appear to be due to DNA fragmentation. Rather, analysis of promoter sequences provides support for the hypothesis that strong constitutive transcription from sequences recognized as rpoD/&#x3c3;(70) consensus-like in E. coli may lead to instability, causing loss of the plasmid or loss of the insert DNA that gives rise to the transcription. Despite widespread use of E. coli to propagate foreign DNA in metagenomic libraries, the effects of in vivo transcriptional activity on clone stability are not well understood. Further work is required to tease apart the effects of transcription from those of gene product toxicity.}, }
@article {pmid26048598, year = {2015}, author = {Fang, H and Huang, C and Zhao, H and Deng, M}, title = {CCLasso: correlation inference for compositional data through Lasso.}, journal = {Bioinformatics (Oxford, England)}, volume = {31}, number = {19}, pages = {3172-3180}, pmid = {26048598}, issn = {1367-4811}, support = {GM59507/GM/NIGMS NIH HHS/United States ; }, mesh = {*Algorithms ; Bacteria/*classification/genetics ; Computational Biology/*methods ; Computer Simulation ; Genomics/methods ; High-Throughput Nucleotide Sequencing/*methods ; Humans ; Metagenomics/*methods ; Microbiota/genetics ; RNA, Ribosomal, 16S/*genetics ; }, abstract = {MOTIVATION: Direct analysis of microbial communities in the environment and human body has become more convenient and reliable owing to the advancements of high-throughput sequencing techniques for 16S rRNA gene profiling. Inferring the correlation relationship among members of microbial communities is of fundamental importance for genomic survey study. Traditional Pearson correlation analysis treating the observed data as absolute abundances of the microbes may lead to spurious results because the data only represent relative abundances. Special care and appropriate methods are required prior to correlation analysis for these compositional data.<br><br>RESULTS: In this article, we first discuss the correlation definition of latent variables for compositional data. We then propose a novel method called CCLasso based on least squares with [Formula: see text] penalty to infer the correlation network for latent variables of compositional data from metagenomic data. An effective alternating direction algorithm from augmented Lagrangian method is used to solve the optimization problem. The simulation results show that CCLasso outperforms existing methods, e.g. SparCC, in edge recovery for compositional data. It also compares well with SparCC in estimating correlation network of microbe species from the Human Microbiome Project.<br><br>CCLasso is open source and freely available from https://github.com/huayingfang/CCLasso under GNU LGPL v3.<br><br>CONTACT: dengmh@pku.edu.cn<br><br>SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.}, }
@article {pmid26035769, year = {2015}, author = {Wright, ML and Starkweather, AR}, title = {Antenatal Microbiome: Potential Contributor to Fetal Programming and Establishment of the Microbiome in Offspring.}, journal = {Nursing research}, volume = {64}, number = {4}, pages = {306-319}, doi = {10.1097/NNR.0000000000000101}, pmid = {26035769}, issn = {1538-9847}, mesh = {Female ; *Fetal Development ; Humans ; Maternal Exposure ; *Microbiota ; Pregnancy ; Pregnancy Complications/*microbiology ; }, abstract = {BACKGROUND: Endogenous and exogenous exposures during fetal development have potential to impact birth and health outcomes of offspring. Accumulating evidence suggests exposures may alter the antenatal microbiome and subsequently alter the microbiome and health of offspring.<br><br>OBJECTIVES: The purpose of this integrative review is to summarize and critically evaluate the current state of knowledge regarding the assessment of the antenatal microbiome on the health of human offspring. The article provides a brief summary of the known factors affecting the human microbiome and studies that assessed relationships between the antenatal microbiome and health outcomes of the offspring.<br><br>METHODS: An integrative review was conducted to examine human research studies that focused on the antenatal microbiome and the health of the offspring using the electronic databases PubMed/MEDLINE and CINAHL from 2004 to the present.<br><br>RESULTS: In addition to the known individual factors that are associated with establishment of the microbiome, the results of the integrative review suggest that medications (including antibiotics) and comorbidities (including infectious diseases, diet, socioeconomic status, and exposure to pollutants) should also be measured.<br><br>DISCUSSION: The composition of the antenatal microbiome at various time points and body sites may be important mediators of short- and long-term health outcomes in offspring. In order to advance our understanding of the role of the antenatal microbiome on health and disease risk of the offspring, it will be important to further elucidate the composition of a healthy microbiome and specific mechanisms that contribute to altered health in later life.}, }
@article {pmid26034276, year = {2015}, author = {Guo, L and McLean, JS and Yang, Y and Eckert, R and Kaplan, CW and Kyme, P and Sheikh, O and Varnum, B and Lux, R and Shi, W and He, X}, title = {Precision-guided antimicrobial peptide as a targeted modulator of human microbial ecology.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {112}, number = {24}, pages = {7569-7574}, pmid = {26034276}, issn = {1091-6490}, support = {R01 DE020102/DE/NIDCR NIH HHS/United States ; R01 DE023810/DE/NIDCR NIH HHS/United States ; 1-R01-DE020102/DE/NIDCR NIH HHS/United States ; 1-R01-DE023810-01/DE/NIDCR NIH HHS/United States ; }, mesh = {Adult ; Anti-Bacterial Agents/pharmacology ; Antimicrobial Cationic Peptides/*pharmacology ; Biofilms/drug effects/growth &amp; development ; Dental Caries/microbiology ; Humans ; Microbial Sensitivity Tests ; Microbiota/*drug effects ; Mouth/microbiology ; Saliva/microbiology ; Streptococcus mutans/*drug effects/pathogenicity/*physiology ; }, abstract = {One major challenge to studying human microbiome and its associated diseases is the lack of effective tools to achieve targeted modulation of individual species and study its ecological function within multispecies communities. Here, we show that C16G2, a specifically targeted antimicrobial peptide, was able to selectively kill cariogenic pathogen Streptococcus mutans with high efficacy within a human saliva-derived in vitro oral multispecies community. Importantly, a significant shift in the overall microbial structure of the C16G2-treated community was revealed after a 24-h recovery period: several bacterial species with metabolic dependency or physical interactions with S. mutans suffered drastic reduction in their abundance, whereas S. mutans' natural competitors, including health-associated Streptococci, became dominant. This study demonstrates the use of targeted antimicrobials to modulate the microbiome structure allowing insights into the key community role of specific bacterial species and also indicates the therapeutic potential of C16G2 to achieve a healthy oral microbiome.}, }
@article {pmid26024217, year = {2015}, author = {Tedjo, DI and Jonkers, DM and Savelkoul, PH and Masclee, AA and van Best, N and Pierik, MJ and Penders, J}, title = {The effect of sampling and storage on the fecal microbiota composition in healthy and diseased subjects.}, journal = {PloS one}, volume = {10}, number = {5}, pages = {e0126685}, pmid = {26024217}, issn = {1932-6203}, mesh = {Adolescent ; Adult ; Aged ; Bacteria/classification/isolation &amp; purification ; Biodiversity ; Colitis, Ulcerative/microbiology ; Crohn Disease/microbiology ; Feces/*microbiology ; Female ; Humans ; Irritable Bowel Syndrome/microbiology ; Male ; *Microbiota ; Middle Aged ; Specimen Handling/*methods ; }, abstract = {Large-scale cohort studies are currently being designed to investigate the human microbiome in health and disease. Adequate sampling strategies are required to limit bias due to shifts in microbial communities during sampling and storage. Therefore, we examined the impact of different sampling and storage conditions on the stability of fecal microbial communities in healthy and diseased subjects. Fecal samples from 10 healthy controls, 10 irritable bowel syndrome and 8 inflammatory bowel disease patients were collected on site, aliquoted immediately after defecation and stored at -80 °C, -20 °C for 1 week, at +4°C or room temperature for 24 hours. Fecal transport swabs (FecalSwab, Copan) were collected and stored for 48-72 hours at room temperature. We used pyrosequencing of the 16S gene to investigate the stability of microbial communities. Alpha diversity did not differ between all storage methods and -80 °C, except for the fecal swabs. UPGMA clustering and principal coordinate analysis showed significant clustering by test subject (p < 0.001) but not by storage method. Bray-Curtis dissimilarity and (un)weighted UniFrac showed a significant higher distance between fecal swabs and -80 °C versus the other methods and -80 °C samples (p < 0.009). The relative abundance of Ruminococcus and Enterobacteriaceae did not differ between the storage methods versus -80 °C, but was higher in fecal swabs (p < 0.05). Storage up to 24 hours (at +4 °C or room temperature) or freezing at -20 °C did not significantly alter the fecal microbial community structure compared to direct freezing of samples from healthy subjects and patients with gastrointestinal disorders.}, }
@article {pmid26016350, year = {2015}, author = {Alekseeva, AE and Brusnigina, NF}, title = {[Metagenomic studies and infectious diseases diagnostics].}, journal = {Zhurnal mikrobiologii, epidemiologii i immunobiologii}, volume = {}, number = {2}, pages = {81-89}, pmid = {26016350}, issn = {0372-9311}, mesh = {Bacterial Infections/*diagnosis/microbiology ; Computational Biology ; High-Throughput Nucleotide Sequencing ; Humans ; *Metagenome ; Molecular Epidemiology ; Mycoses/*diagnosis/microbiology ; Parasitic Diseases/*diagnosis/parasitology ; Virus Diseases/*diagnosis/virology ; }, abstract = {Principles of mass parallel sequencing, otherwise called next generation sequencing (NGS), appeared at the beginning of 2000s and were realized in dozens of NGS platforms. High performance and sequencing speed of NGS platforms opened wide horizons for scientists in the field of genomic studies, including metagenomic, first of all related to studies of structure of various microbiocenoses. Dozens of studies dedicated to studies of microbiome and virome of various biotopes of humans in normal state and pathology by using NGS platforms have appeared, forming novel conceptions on pathogenesis and epidemiology ofvarious infectious diseases. Significant cost reduction of the analysis facilitates expansion of sphere of application for NGS technologies not only in the field of fundamental, but also applied microbiologic studies, including etiologic diagnostics of infectious diseases. Due to the increase of the number of cases of infectious diseases, that do not have a typical clinical presentation, use of metagenomic approach is of particular importance, allowing to carry out detection of a wide spectrum of causative agents of bacterial, viral and parasitic infections. Technologic features of mass parallel sequencing platform, main methods of metagenomic studies and bioinformatics approaches, used for the analysis of data obtained, are presented in the review. Studies on healthy human microbiome and in pathology are described; possibilities and perspectives of metagenomic approach application in diagnos- tics and system of epidemiologic control of infectious diseases are examined.}, }
@article {pmid26012569, year = {2015}, author = {Manzo, VE and Bhatt, AS}, title = {The human microbiome in hematopoiesis and hematologic disorders.}, journal = {Blood}, volume = {126}, number = {3}, pages = {311-318}, pmid = {26012569}, issn = {1528-0020}, support = {K08 CA184420/CA/NCI NIH HHS/United States ; }, mesh = {Bacteria/classification/genetics/*isolation &amp; purification ; Fungi/classification/genetics/*isolation &amp; purification ; Hematologic Diseases/genetics/*microbiology ; Hematopoiesis/*physiology ; Humans ; *Microbiota ; }, abstract = {Humans are now understood to be in complex symbiosis with a diverse ecosystem of microbial organisms, including bacteria, viruses, and fungi. Efforts to characterize the role of these microorganisms, commonly referred as the microbiota, in human health have sought to answer the fundamental questions of what organisms are present, how are they functioning to interact with human cells, and by what mechanism are these interactions occurring. In this review, we describe recent efforts to describe the microbiota in healthy and diseased individuals, summarize the role of various molecular technologies (ranging from 16S ribosomal RNA to shotgun metagenomic sequencing) in enumerating the community structure of the microbiota, and explore known interactions between the microbiota and humans, with a focus on the microbiota's role in hematopoiesis and hematologic diseases.}, }
@article {pmid26003843, year = {2015}, author = {Barin, JG and Tobias, LD and Peterson, DA}, title = {The microbiome and autoimmune disease: Report from a Noel R. Rose Colloquium.}, journal = {Clinical immunology (Orlando, Fla.)}, volume = {159}, number = {2}, pages = {183-188}, doi = {10.1016/j.clim.2015.05.009}, pmid = {26003843}, issn = {1521-7035}, mesh = {Animals ; Autoimmune Diseases/*immunology/microbiology ; *Diet ; Epigenesis, Genetic ; Female ; Gastrointestinal Microbiome/genetics/*immunology ; Humans ; Immunity, Mucosal/*immunology ; Male ; Mice ; Microbiota/genetics/immunology ; Sex Factors ; }, abstract = {Although the mechanisms by which the human microbiome influences the onset and progression of autoimmune diseases remain to be determined, established animal models of autoimmune diseases indicate that local and systemic bidirectional interactions with the microbiome play a signaling or promoting role through the immune system. Whether alterations in the microbiome are a pathogenic cause or simply an effect of inflammation and autoimmune disease remains an essential question to be addressed in disease-specific research, as well as whether particular conditions of the microbiome promote health or promote disease. Future research in this area needs to account for sex differences in microbiome composition because autoimmune diseases disproportionately affect women. Probiotic and other treatments that manipulate assemblage of the microbiome may offer methods of preventing or mitigating the effects of autoimmune disease.}, }
@article {pmid26002029, year = {2015}, author = {Panzer, AR and Lynch, SV}, title = {Influence and effect of the human microbiome in allergy and asthma.}, journal = {Current opinion in rheumatology}, volume = {27}, number = {4}, pages = {373-380}, doi = {10.1097/BOR.0000000000000191}, pmid = {26002029}, issn = {1531-6963}, support = {AI089473-01/AI/NIAID NIH HHS/United States ; AI113916/AI/NIAID NIH HHS/United States ; U10 HL098107-05/HL/NHLBI NIH HHS/United States ; }, mesh = {Asthma/immunology/*microbiology ; Environmental Exposure/adverse effects ; Gastrointestinal Tract/microbiology ; Humans ; Hypersensitivity/immunology/*microbiology ; *Microbiota ; }, abstract = {PURPOSE OF REVIEW: Studies have illustrated that the healthy human microbiome (i.e. the communities of microbes, their genomic content and interaction with the host) plays a role in the maintenance of immune homeostasis. Perturbation of these communities is an emerging characteristic of an increasing number of inflammatory diseases. The goal of this article is to review the current literature on both respiratory and gut microbiomes and their established relationship with allergy and asthma.<br><br>RECENT FINDINGS: Multiple studies have demonstrated airway microbiota dysbiosis, characterized by Proteobacteria expansion in the lower airways, to be a consistent trait of established adult asthma. Members of this phylum are associated with disease features such as bronchial hyperreactivity or corticosteroid resistance. Emerging evidence implicates the neonatal gut microbiome as playing a significant role in the development of childhood atopy, a common precursor to asthma. Murine studies have demonstrated that specific bacterial species (e.g. Lactobacillus johnsonii, Bacteroides fragilis) and microbial metabolites (e.g. the short-chain fatty acid propionate), when supplemented to animals, confer protection against allergen-induced airway disorders.<br><br>SUMMARY: The emerging view of atopy and asthma is one consistently related to inappropriate microbial community composition and function in both the airway and gastrointestinal tract. This opens up the possibility that strategies to rationally manipulate microbiota at these sites may represent a novel approach to disease prevention or management.}, }
@article {pmid25991836, year = {2015}, author = {Coburn, B and Guttman, DS}, title = {The human microbiome.}, journal = {CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne}, volume = {187}, number = {11}, pages = {825}, pmid = {25991836}, issn = {1488-2329}, mesh = {Bacterial Infections/microbiology/physiopathology ; Diet ; Exercise/physiology ; Health Status ; Humans ; Immunocompetence/*immunology ; *Life Style ; Microbiota/*immunology/*physiology ; Probiotics/*administration &amp; dosage ; Risk Factors ; Sensitivity and Specificity ; }, }
@article {pmid25981789, year = {2015}, author = {Rampelli, S and Schnorr, SL and Consolandi, C and Turroni, S and Severgnini, M and Peano, C and Brigidi, P and Crittenden, AN and Henry, AG and Candela, M}, title = {Metagenome Sequencing of the Hadza Hunter-Gatherer Gut Microbiota.}, journal = {Current biology : CB}, volume = {25}, number = {13}, pages = {1682-1693}, doi = {10.1016/j.cub.2015.04.055}, pmid = {25981789}, issn = {1879-0445}, mesh = {Amino Acid Sequence ; Amino Acids/biosynthesis/metabolism ; Base Sequence ; *Biological Evolution ; *Diet, Paleolithic ; Drug Resistance, Microbial/genetics ; Ethnicity/*genetics ; Gastrointestinal Microbiome/*genetics/*physiology ; High-Throughput Nucleotide Sequencing ; Humans ; Italy ; Metagenome/*genetics ; Molecular Sequence Data ; Principal Component Analysis ; Statistics, Nonparametric ; Tanzania ; White People/*genetics ; }, abstract = {Through human microbiome sequencing, we can better understand how host evolutionary and ontogenetic history is reflected in the microbial function. However, there has been no information on the gut metagenome configuration in hunter-gatherer populations, posing a gap in our knowledge of gut microbiota (GM)-host mutualism arising from a lifestyle that describes over 90% of human evolutionary history. Here, we present the first metagenomic analysis of GM from Hadza hunter-gatherers of Tanzania, showing a unique enrichment in metabolic pathways that aligns with the dietary and environmental factors characteristic of their foraging lifestyle. We found that the Hadza GM is adapted for broad-spectrum carbohydrate metabolism, reflecting the complex polysaccharides in their diet. Furthermore, the Hadza GM is equipped for branched-chain amino acid degradation and aromatic amino acid biosynthesis. Resistome functionality demonstrates the existence of antibiotic resistance genes in a population with little antibiotic exposure, indicating the ubiquitous presence of environmentally derived resistances. Our results demonstrate how the functional specificity of the GM correlates with certain environment and lifestyle factors and how complexity from the exogenous environment can be balanced by endogenous homeostasis. The Hadza gut metagenome structure allows us to appreciate the co-adaptive functional role of the GM in complementing the human physiology, providing a better understanding of the versatility of human life and subsistence.}, }
@article {pmid25979893, year = {2015}, author = {Bisanz, JE and Enos, MK and PrayGod, G and Seney, S and Macklaim, JM and Chilton, S and Willner, D and Knight, R and Fusch, C and Fusch, G and Gloor, GB and Burton, JP and Reid, G}, title = {Microbiota at Multiple Body Sites during Pregnancy in a Rural Tanzanian Population and Effects of Moringa-Supplemented Probiotic Yogurt.}, journal = {Applied and environmental microbiology}, volume = {81}, number = {15}, pages = {4965-4975}, pmid = {25979893}, issn = {1098-5336}, mesh = {Bacteria/*classification/genetics/*isolation &amp; purification ; Cluster Analysis ; DNA, Bacterial/chemistry/genetics ; DNA, Ribosomal/chemistry/genetics ; Diet/*methods ; Female ; Gastrointestinal Tract/microbiology ; Humans ; Infant ; Infant, Newborn ; *Microbiota ; Milk, Human/microbiology ; Molecular Sequence Data ; *Moringa ; Mouth Mucosa/microbiology ; Phylogeny ; Pregnancy ; Probiotics/*administration &amp; dosage ; RNA, Ribosomal, 16S/genetics ; Rural Population ; Sequence Analysis, DNA ; Tanzania ; Vagina/microbiology ; *Yogurt ; }, abstract = {The nutritional status of pregnant women is vital for healthy outcomes and is a concern for a large proportion of the world's population. The role of the microbiota in pregnancy and nutrition is a promising new area of study with potential health ramifications. In many African countries, maternal and infant death and morbidity are associated with malnutrition. Here, we assess the influence of probiotic yogurt containing Lactobacillus rhamnosus GR-1, supplemented with Moringa plant as a source of micronutrients, on the health and oral, gut, vaginal, and milk microbiotas of 56 pregnant women in Tanzania. In an open-label study design, 26 subjects received yogurt daily, and 30 were untreated during the last two trimesters and for 1 month after birth. Samples were analyzed using 16S rRNA gene sequencing, and dietary recalls were recorded. Women initially categorized as nourished or undernourished consumed similar calories and macronutrients, which may explain why there was no difference in the microbiota at any body site. Consumption of yogurt increased the relative abundance of Bifidobacterium and decreased Enterobacteriaceae in the newborn feces but had no effect on the mother's microbiota at any body site. The microbiota of the oral cavity and GI tract remained stable over pregnancy, but the vaginal microbiota showed a significant increase in diversity leading up to and after birth. In summary, daily micronutrient-supplemented probiotic yogurt provides a safe, affordable food for pregnant women in rural Tanzania, and the resultant improvement in the gut microbial profile of infants is worthy of further study.}, }
@article {pmid25977840, year = {2015}, author = {Zhao, Y and Dua, P and Lukiw, WJ}, title = {Microbial Sources of Amyloid and Relevance to Amyloidogenesis and Alzheimer's Disease (AD).}, journal = {Journal of Alzheimer's disease &amp; Parkinsonism}, volume = {5}, number = {1}, pages = {177}, pmid = {25977840}, issn = {2161-0460}, support = {R01 EY006311/EY/NEI NIH HHS/United States ; R01 AG018031/AG/NIA NIH HHS/United States ; P50 AG016573/AG/NIA NIH HHS/United States ; R01 AG038834/AG/NIA NIH HHS/United States ; P30 GM103340/GM/NIGMS NIH HHS/United States ; }, abstract = {Since the inception of the human microbiome project (HMP) by the US National Institutes of Health (NIH) in 2007 there has been a keen resurgence in our recognition of the human microbiome and its contribution to development, immunity, neurophysiology, metabolic and nutritive support to central nervous system (CNS) health and disease. What is not generally appreciated is that (i) the ~10[14] microbial cells that comprise the human microbiome outnumber human host cells by approximately one hundred-to-one; (ii) together the microbial genes of the microbiome outnumber human host genes by about one hundred-and-fifty to one; (iii) collectively these microbes constitute the largest 'diffuse organ system' in the human body, more metabolically active than the liver; strongly influencing host nutritive-, innate-immune, neuroinflammatory-, neuromodulatory- and neurotransmission-functions; and (iv) that these microbes actively secrete highly complex, immunogenic mixtures of lipopolysaccharide (LPS) and amyloid from their outer membranes into their immediate environment. While secreted LPS and amyloids are generally quite soluble as monomers over time they form into highly insoluble fibrous protein aggregates that are implicated in the progressive degenerative neuropathology of several common, age-related disorders of the human CNS including Alzheimer's disease (AD). This general commentary-perspective paper will highlight some recent findings on microbial-derived secreted LPS and amyloids and the potential contribution of these neurotoxic and proinflammatory microbial exudates to age-related inflammatory amyloidogenesis and neurodegeneration, with specific reference to AD wherever possible.}, }
@article {pmid25977424, year = {2015}, author = {Subhadra, B and Krier, J and Hofstee, K and Monsul, N and Berkes, E}, title = {Draft Whole-Genome Sequence of Lactobacillus fermentum LfQi6, Derived from the Human Microbiome.}, journal = {Genome announcements}, volume = {3}, number = {3}, pages = {}, pmid = {25977424}, issn = {2169-8287}, abstract = {We report a 2.21-Mbp draft whole-genome sequence of Lactobacillus fermentum Qi6 (LfQi6). This strain demonstrates activity against pathogenic biofilms, enhances the skin barrier, and upregulates innate immune defenses. The genome sequence information of this strain will help to identify molecules that hold promise for the discovery of novel therapeutics for dermatological disorders.}, }
@article {pmid25974348, year = {2015}, author = {Blaser, MJ}, title = {Studying microbiology with Glenn F. Webb.}, journal = {Mathematical biosciences and engineering : MBE}, volume = {12}, number = {4}, pages = {xvii-xxii}, doi = {10.3934/mbe.2015.12.4xvii}, pmid = {25974348}, issn = {1551-0018}, mesh = {Bacterial Infections/*history ; Computational Biology/*history ; Epidemiology/*history ; History, 20th Century ; History, 21st Century ; Humans ; Mathematics/*history ; Microbiology/*history ; United States ; }, abstract = {I began working with Glenn F. Webb in 1997. At that time, I was on the faculty of Vanderbilt University, in the School of Medicine, in the Department of Medicine, in its Division of Infectious Diseases. As with mathematics, modern medicine has its different disciplines (e.g. Surgery and Internal Medicine), and then further subdivisions (e.g. Cardiology and Infectious Diseases). Within Internal Medicine, most of the divisions are based on the treatment of conditions that relate to a single organ or group of organs -- the heart, the lungs, the kidneys, the digestive system. But the discipline of Infectious Diseases was based on a different concept: the war between humans and microbes.}, }
@article {pmid25974301, year = {2015}, author = {Fujimura, KE and Lynch, SV}, title = {Microbiota in allergy and asthma and the emerging relationship with the gut microbiome.}, journal = {Cell host &amp; microbe}, volume = {17}, number = {5}, pages = {592-602}, pmid = {25974301}, issn = {1934-6069}, support = {P01 AI089473/AI/NIAID NIH HHS/United States ; UM1 AI114271/AI/NIAID NIH HHS/United States ; 1P01AI089473/AI/NIAID NIH HHS/United States ; UM1AI114271/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Dysbiosis/*complications/*immunology ; *Environmental Microbiology ; Gastrointestinal Tract/*microbiology ; Humans ; Hypersensitivity/*microbiology ; Microbiota/*immunology ; Respiratory System/*microbiology ; }, abstract = {Asthma and atopy, classically associated with hyper-activation of the T helper 2 (Th2) arm of adaptive immunity, are among the most common chronic illnesses worldwide. Emerging evidence relates atopy and asthma to the composition and function of the human microbiome, the collection of microbes that reside in and on and interact with the human body. The ability to interrogate microbial ecology of the human host is due in large part to recent technological developments that permit identification of microbes and their products using culture-independent molecular detection techniques. In this review we explore the roles of respiratory, gut, and environmental microbiomes in asthma and allergic disease development, manifestation, and attenuation. Though still a relatively nascent field of research, evidence to date suggests that the airway and/or gut microbiome may represent fertile targets for prevention or management of allergic asthma and other diseases in which adaptive immune dysfunction is a prominent feature.}, }
@article {pmid25970037, year = {2016}, author = {Cervantes, JL and Hong, BY}, title = {Dysbiosis and Immune Dysregulation in Outer Space.}, journal = {International reviews of immunology}, volume = {35}, number = {1}, pages = {67-82}, doi = {10.3109/08830185.2015.1027821}, pmid = {25970037}, issn = {1563-5244}, mesh = {Astronauts ; Bacteroides/immunology/radiation effects ; Candida albicans/immunology/pathogenicity ; Clostridiales/immunology/pathogenicity ; Clostridioides difficile/immunology/pathogenicity ; Cosmic Radiation/adverse effects ; Cytokines/immunology/metabolism/radiation effects ; Dendritic Cells/metabolism/radiation effects ; Dietary Supplements ; Dysbiosis/*immunology ; Escherichia coli/immunology/pathogenicity ; Gastrointestinal Microbiome/*immunology/radiation effects ; Helicobacter hepaticus/immunology/pathogenicity ; Humans ; Immunity/*radiation effects ; Leukocytes/metabolism/radiation effects ; Probiotics/therapeutic use ; Pseudomonas aeruginosa/immunology/pathogenicity ; Salmonella typhimurium/immunology/pathogenicity ; *Space Flight ; Virulence ; Weightlessness/*adverse effects ; }, abstract = {In space, the lifestyle, relative sterility of spaceship and extreme environmental stresses, such as microgravity and cosmic radiation, can compromise the balance between human body and human microbiome. An astronaut's body during spaceflight encounters increased risk for microbial infections and conditions because of immune dysregulation and altered microbiome, i.e. dysbiosis. This risk is further heightened by increase in virulence of pathogens in microgravity. Health status of astronauts might potentially benefit from maintaining a healthy microbiome by specifically managing their diet on space in addition to probiotic therapies. This review focuses on the current knowledge/understanding of how spaceflight affects human immunity and microbiome.}, }
@article {pmid25968082, year = {2015}, author = {Nenoff, P and Krüger, C and Mayser, P}, title = {[Cutaneous Malassezia infections and Malassezia associated dermatoses: An update].}, journal = {Der Hautarzt; Zeitschrift fur Dermatologie, Venerologie, und verwandte Gebiete}, volume = {66}, number = {6}, pages = {465-84; quiz 485-6}, pmid = {25968082}, issn = {1432-1173}, mesh = {Antifungal Agents/adverse effects/therapeutic use ; Dermatitis, Atopic/*diagnosis/drug therapy ; Dermatitis, Seborrheic/*diagnosis/drug therapy ; Itraconazole/adverse effects/therapeutic use ; Ketoconazole/adverse effects/therapeutic use ; *Malassezia/ultrastructure ; Tinea Versicolor/*diagnosis/drug therapy ; }, abstract = {The lipophilic yeast fungus Malassezia (M.) spp. is the only fungal genus or species which is part of the physiological human microbiome. Today, at least 14 different Malassezia species are known; most of them can only be identified using molecular biological techniques. As a facultative pathogenic microorganism, Malassezia represents the causative agent both of superficial cutaneous infections and of blood stream infections. Pityriasis versicolor is the probably most frequent infection caused by Malassezia. Less common, Malassezia folliculitis occurs. There is only an episodic report on Malassezia-induced onychomycosis. Seborrhoeic dermatitis represents a Malassezia-associated inflammatory dermatosis. In addition, Malassezia allergenes should be considered as the trigger of "Head-Neck"-type atopic dermatitis. Ketoconazole possesses the strongest in vitro activity against Malassezia, and represents the treatment of choice for topical therapy of pityriasis versicolor. Alternatives include other azole antifungals but also the allylamine terbinafine and the hydroxypyridone antifungal agent ciclopirox olamine. "Antiseborrhoeic" agents, e.g. zinc pyrithione, selenium disulfide, and salicylic acid, are also effective in pityriasis versicolor. The drug of choice for oral treatment of pityriasis versicolor is itraconazole; an effective alternative represents fluconazole. Seborrhoeic dermatitis is best treated with topical medication, including topical corticosteroids and antifungal agents like ketoconazole or sertaconazole. Calcineurin inhibitors, e.g. pimecrolimus and tacrolimus, are reliable in seborrhoeic dermatitis, however are used off-label.}, }
@article {pmid25964341, year = {2015}, author = {Franzosa, EA and Huang, K and Meadow, JF and Gevers, D and Lemon, KP and Bohannan, BJ and Huttenhower, C}, title = {Identifying personal microbiomes using metagenomic codes.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {112}, number = {22}, pages = {E2930-8}, pmid = {25964341}, issn = {1091-6490}, support = {R01 AI101018/AI/NIAID NIH HHS/United States ; U54HG004969/HG/NHGRI NIH HHS/United States ; HHSN272200900018C/AI/NIAID NIH HHS/United States ; P50 GM098911/GM/NIGMS NIH HHS/United States ; HHSN272200900018C//PHS HHS/United States ; R01 HG005969/HG/NHGRI NIH HHS/United States ; U54 HG004969/HG/NHGRI NIH HHS/United States ; R01HG005969/HG/NHGRI NIH HHS/United States ; P50GM098911/GM/NIGMS NIH HHS/United States ; }, mesh = {Confidentiality/standards/trends ; Genetic Markers/*genetics ; *Genetic Variation ; Humans ; Metagenomics/*methods ; Microbiota/*genetics ; Models, Genetic ; Precision Medicine/*methods ; }, abstract = {Community composition within the human microbiome varies across individuals, but it remains unknown if this variation is sufficient to uniquely identify individuals within large populations or stable enough to identify them over time. We investigated this by developing a hitting set-based coding algorithm and applying it to the Human Microbiome Project population. Our approach defined body site-specific metagenomic codes: sets of microbial taxa or genes prioritized to uniquely and stably identify individuals. Codes capturing strain variation in clade-specific marker genes were able to distinguish among 100s of individuals at an initial sampling time point. In comparisons with follow-up samples collected 30-300 d later, ∼30% of individuals could still be uniquely pinpointed using metagenomic codes from a typical body site; coincidental (false positive) matches were rare. Codes based on the gut microbiome were exceptionally stable and pinpointed >80% of individuals. The failure of a code to match its owner at a later time point was largely explained by the loss of specific microbial strains (at current limits of detection) and was only weakly associated with the length of the sampling interval. In addition to highlighting patterns of temporal variation in the ecology of the human microbiome, this work demonstrates the feasibility of microbiome-based identifiability-a result with important ethical implications for microbiome study design. The datasets and code used in this work are available for download from huttenhower.sph.harvard.edu/idability.}, }
@article {pmid25957511, year = {2015}, author = {Sizova, MV and Doerfert, SN and Gavrish, E and Epstein, SS}, title = {TM7 detection in human microbiome: Are PCR primers and FISH probes specific enough?.}, journal = {Journal of microbiological methods}, volume = {114}, number = {}, pages = {51-53}, pmid = {25957511}, issn = {1872-8359}, support = {R21 DE018026/DE/NIDCR NIH HHS/United States ; RC1 DE020707/DE/NIDCR NIH HHS/United States ; 1RC1DE020707-01/DE/NIDCR NIH HHS/United States ; 3 R21 DE018026-02S1/DE/NIDCR NIH HHS/United States ; }, mesh = {Bacteria/*classification/*genetics ; DNA Primers/*genetics ; Female ; Humans ; In Situ Hybridization, Fluorescence/*methods ; *Microbiota ; Mouth/microbiology ; Oligonucleotide Probes/*genetics ; Polymerase Chain Reaction/*methods ; Sensitivity and Specificity ; Vagina/microbiology ; }, abstract = {TM7 appears important and omnipresent because it is repeatedly detected by molecular techniques in diverse environments. Here we report that most of primers and FISH probes thought to be TM7-specific do hybridize with multiple species from oral and vaginal cavity. This calls for re-examination of TM7 distribution and abundance.}, }
@article {pmid25957468, year = {2015}, author = {Zhao, N and Chen, J and Carroll, IM and Ringel-Kulka, T and Epstein, MP and Zhou, H and Zhou, JJ and Ringel, Y and Li, H and Wu, MC}, title = {Testing in Microbiome-Profiling Studies with MiRKAT, the Microbiome Regression-Based Kernel Association Test.}, journal = {American journal of human genetics}, volume = {96}, number = {5}, pages = {797-807}, pmid = {25957468}, issn = {1537-6605}, support = {K01 DK092330/DK/NIDDK NIH HHS/United States ; R01HG007508/HG/NHGRI NIH HHS/United States ; S10 OD020069/OD/NIH HHS/United States ; R01HG006139/HG/NHGRI NIH HHS/United States ; R01 HG006139/HG/NHGRI NIH HHS/United States ; P30DK03498/DK/NIDDK NIH HHS/United States ; K01DK092330/DK/NIDDK NIH HHS/United States ; R01GM097505/GM/NIGMS NIH HHS/United States ; R01 GM097505/GM/NIGMS NIH HHS/United States ; R01 HG007508/HG/NHGRI NIH HHS/United States ; P30 DK034987/DK/NIDDK NIH HHS/United States ; }, mesh = {Computer Simulation ; *Genetics, Population ; High-Throughput Nucleotide Sequencing ; Humans ; Microbiota/*genetics ; *Models, Statistical ; Phylogeny ; Polymorphism, Single Nucleotide ; Software ; }, abstract = {High-throughput sequencing technology has enabled population-based studies of the role of the human microbiome in disease etiology and exposure response. Distance-based analysis is a popular strategy for evaluating the overall association between microbiome diversity and outcome, wherein the phylogenetic distance between individuals' microbiome profiles is computed and tested for association via permutation. Despite their practical popularity, distance-based approaches suffer from important challenges, especially in selecting the best distance and extending the methods to alternative outcomes, such as survival outcomes. We propose the microbiome regression-based kernel association test (MiRKAT), which directly regresses the outcome on the microbiome profiles via the semi-parametric kernel machine regression framework. MiRKAT allows for easy covariate adjustment and extension to alternative outcomes while non-parametrically modeling the microbiome through a kernel that incorporates phylogenetic distance. It uses a variance-component score statistic to test for the association with analytical p value calculation. The model also allows simultaneous examination of multiple distances, alleviating the problem of choosing the best distance. Our simulations demonstrated that MiRKAT provides correctly controlled type I error and adequate power in detecting overall association. "Optimal" MiRKAT, which considers multiple candidate distances, is robust in that it suffers from little power loss in comparison to when the best distance is used and can achieve tremendous power gain in comparison to when a poor distance is chosen. Finally, we applied MiRKAT to real microbiome datasets to show that microbial communities are associated with smoking and with fecal protease levels after confounders are controlled for.}, }
@article {pmid25957158, year = {2015}, author = {Chase, D and Goulder, A and Zenhausern, F and Monk, B and Herbst-Kralovetz, M}, title = {The vaginal and gastrointestinal microbiomes in gynecologic cancers: a review of applications in etiology, symptoms and treatment.}, journal = {Gynecologic oncology}, volume = {138}, number = {1}, pages = {190-200}, doi = {10.1016/j.ygyno.2015.04.036}, pmid = {25957158}, issn = {1095-6859}, mesh = {Female ; Gastrointestinal Tract/*microbiology ; Genital Neoplasms, Female/*microbiology ; Humans ; Microbiota ; Vagina/*microbiology ; }, abstract = {The human microbiome is the collection of microorganisms in the body that exist in a mutualistic relationship with the host. Recent studies indicate that perturbations in the microbiome may be implicated in a number of diseases, including cancer. More specifically, changes in the gut and vaginal microbiomes may be associated with a variety of gynecologic cancers, including cervical cancer, uterine cancer, and ovarian cancer. Current research and gaps in knowledge regarding the association between the gut and vaginal microbiomes and the development, progression, and treatment of gynecologic cancers are reviewed here. In addition, the potential use of probiotics to manage symptoms of these gynecologic cancers is discussed. A better understanding of how the microbiome composition is altered at these sites and its interaction with the host may aid in prevention, optimization of current therapies, development of new therapeutic agents and/or dosing regimens, and possibly limit the side effects associated with cancer treatment.}, }
@article {pmid25955884, year = {2016}, author = {Kachrimanidou, M and Sarmourli, T and Skoura, L and Metallidis, S and Malisiovas, N}, title = {Clostridium difficile infection: New insights into therapeutic options.}, journal = {Critical reviews in microbiology}, volume = {42}, number = {5}, pages = {773-779}, doi = {10.3109/1040841X.2015.1027171}, pmid = {25955884}, issn = {1549-7828}, mesh = {Animals ; Anti-Bacterial Agents/*administration &amp; dosage ; Bacterial Proteins/genetics/metabolism ; Clostridioides difficile/*drug effects/genetics/metabolism ; Clostridium Infections/*drug therapy/microbiology ; Humans ; }, abstract = {Clostridium difficile infection (CDI) is an important cause of mortality and morbidity in healthcare settings and represents a major social and economic burden. The major virulence determinants are large clostridial toxins, toxin A (TcdA) and toxin B (TcdB), encoded within the pathogenicity locus. Traditional therapies, such as metronidazole and vancomycin, frequently lead to a vicious circle of recurrences due to their action against normal human microbiome. New disease management strategies together with the development of novel therapeutic and containment approaches are needed in order to better control outbreaks and treat patients. This article provides an overview of currently available CDI treatment options and discusses the most promising therapies under development.}, }
@article {pmid25950865, year = {2015}, author = {Horz, HP}, title = {Archaeal Lineages within the Human Microbiome: Absent, Rare or Elusive?.}, journal = {Life (Basel, Switzerland)}, volume = {5}, number = {2}, pages = {1333-1345}, pmid = {25950865}, issn = {2075-1729}, abstract = {Archaea are well-recognized components of the human microbiome. However, they appear to be drastically underrepresented compared to the high diversity of bacterial taxa which can be found on various human anatomic sites, such as the gastrointestinal environment, the oral cavity and the skin. As our "microbial" view of the human body, including the methodological concepts used to describe them, has been traditionally biased on bacteria, the question arises whether our current knowledge reflects the actual ratio of archaea versus bacteria or whether we have failed so far to unravel the full diversity of human-associated archaea. This review article hypothesizes that distinct archaeal lineages within humans exist, which still await our detection. First, previously unrecognized taxa might be quite common but they have eluded conventional detection methods. Two recent prime examples are described that demonstrate that this might be the case for specific archaeal lineages. Second, some archaeal taxa might be overlooked because they are rare and/or in low abundance. Evidence for this exists for a broad range of phylogenetic lineages, however we currently do not know whether these sporadically appearing organisms are mere transients or important members of the so called "rare biosphere" with probably basic ecosystem functions. Lastly, evidence exists that different human populations harbor different archaeal taxa and/or the abundance and activity of shared archaeal taxa may differ and thus their impact on the overall microbiome. This research line is rather unexplored and warrants further investigation. While not recapitulating exhaustively all studies on archaeal diversity in humans, this review highlights pertinent recent findings that show that the choice of appropriate methodological approaches and the consideration of different human populations may lead to the detection of archaeal lineages previously not associated with humans. This in turn will help understand variations found in the overall microbiomes from different individuals and ultimately may lead to the emergence of novel concepts/mechanisms impacting human health.}, }
@article {pmid25942663, year = {2015}, author = {Yu, Y and Champer, J and Beynet, D and Kim, J and Friedman, AJ}, title = {The role of the cutaneous microbiome in skin cancer: lessons learned from the gut.}, journal = {Journal of drugs in dermatology : JDD}, volume = {14}, number = {5}, pages = {461-465}, pmid = {25942663}, issn = {1545-9616}, mesh = {Animals ; Gastrointestinal Tract/microbiology ; Humans ; Inflammation/microbiology/pathology ; *Microbiota ; Probiotics/administration &amp; dosage ; Skin/*microbiology/pathology ; Skin Neoplasms/*microbiology/pathology ; }, abstract = {The human microbiome has recently gained prominence as a major factor in health and disease. Here we review the literature regarding the microbiome and cancer and suggest how the microbiome may be manipulated for improved health outcomes. The gut microbiome has been relatively well studied, and the mechanisms of how it may increase or decrease the risk of certain cancers may apply to the skin microbiome. Additionally, the gut microbiome may directly impact the risk of cancer in the skin and other organs by promoting systemic inflammation. The skin microbiome itself is as diverse as the gut microbiome, but research has just begun to unravel its influence on the host. Like the gut microbiome, it affects the risk for several diseases, including cancer. By using healthpromoting strains from the microbiome in oral or topical probiotics, it may be possible to reduce the risk of skin cancer and perhaps even increase the likelihood of successful treatment.}, }
@article {pmid25935300, year = {2015}, author = {Tan, J and Zuniga, C and Zengler, K}, title = {Unraveling interactions in microbial communities - from co-cultures to microbiomes.}, journal = {Journal of microbiology (Seoul, Korea)}, volume = {53}, number = {5}, pages = {295-305}, pmid = {25935300}, issn = {1976-3794}, mesh = {Bacteria/*genetics/metabolism ; Biodiversity ; Ecosystem ; Humans ; Metagenome ; *Microbial Consortia ; Microbiota/*physiology ; Phylogeny ; RNA, Ribosomal, 16S/genetics ; }, abstract = {Microorganisms do not exist in isolation in the environment. Instead, they form complex communities among themselves as well as with their hosts. Different forms of interactions not only shape the composition of these communities but also define how these communities are established and maintained. The kinds of interaction a bacterium can employ are largely encoded in its genome. This allows us to deploy a genomescale modeling approach to understand, and ultimately predict, the complex and intertwined relationships in which microorganisms engage. So far, most studies on microbial communities have been focused on synthetic co-cultures and simple communities. However, recent advances in molecular and computational biology now enable bottom up methods to be deployed for complex microbial communities from the environment to provide insight into the intricate and dynamic interactions in which microorganisms are engaged. These methods will be applicable for a wide range of microbial communities involved in industrial processes, as well as understanding, preserving and reconditioning natural microbial communities present in soil, water, and the human microbiome.}, }
@article {pmid25934071, year = {2015}, author = {Segal, LN and Blaser, MJ}, title = {Harnessing the Early-Life Microbiota to Protect Children with Cystic Fibrosis.}, journal = {The Journal of pediatrics}, volume = {167}, number = {1}, pages = {16-18.e1}, pmid = {25934071}, issn = {1097-6833}, support = {UL1 TR001445/TR/NCATS NIH HHS/United States ; UH2 AR57506/AR/NIAMS NIH HHS/United States ; T35 DK007421/DK/NIDDK NIH HHS/United States ; UH2 AR057506/AR/NIAMS NIH HHS/United States ; K23 AI102970/AI/NIAID NIH HHS/United States ; UL1 TR000038/TR/NCATS NIH HHS/United States ; R01 DK090989/DK/NIDDK NIH HHS/United States ; }, mesh = {Cystic Fibrosis/*microbiology ; Humans ; Intestines/*microbiology ; *Microbiota ; Respiratory System/*microbiology ; }, }
@article {pmid25932026, year = {2015}, author = {Kutikhin, AG and Yuzhalin, AE}, title = {Editorial: recent discoveries in evolutionary and genomic microbiology.}, journal = {Frontiers in microbiology}, volume = {6}, number = {}, pages = {323}, pmid = {25932026}, issn = {1664-302X}, }
@article {pmid25926546, year = {2015}, author = {Ames, SK and Gardner, SN and Marti, JM and Slezak, TR and Gokhale, MB and Allen, JE}, title = {Using populations of human and microbial genomes for organism detection in metagenomes.}, journal = {Genome research}, volume = {25}, number = {7}, pages = {1056-1067}, pmid = {25926546}, issn = {1549-5469}, mesh = {Computational Biology/methods ; Databases, Nucleic Acid ; *Genome, Microbial ; Humans ; *Metagenome ; Metagenomics/*methods ; *Microbiota ; ROC Curve ; }, abstract = {Identifying causative disease agents in human patients from shotgun metagenomic sequencing (SMS) presents a powerful tool to apply when other targeted diagnostics fail. Numerous technical challenges remain, however, before SMS can move beyond the role of research tool. Accurately separating the known and unknown organism content remains difficult, particularly when SMS is applied as a last resort. The true amount of human DNA that remains in a sample after screening against the human reference genome and filtering nonbiological components left from library preparation has previously been underreported. In this study, we create the most comprehensive collection of microbial and reference-free human genetic variation available in a database optimized for efficient metagenomic search by extracting sequences from GenBank and the 1000 Genomes Project. The results reveal new human sequences found in individual Human Microbiome Project (HMP) samples. Individual samples contain up to 95% human sequence, and 4% of the individual HMP samples contain 10% or more human reads. Left unidentified, human reads can complicate and slow down further analysis and lead to inaccurately labeled microbial taxa and ultimately lead to privacy concerns as more human genome data is collected.}, }
@article {pmid25911234, year = {2015}, author = {Polke, M and Hube, B and Jacobsen, ID}, title = {Candida survival strategies.}, journal = {Advances in applied microbiology}, volume = {91}, number = {}, pages = {139-235}, doi = {10.1016/bs.aambs.2014.12.002}, pmid = {25911234}, issn = {0065-2164}, mesh = {Biofilms/*growth &amp; development ; Candida/genetics/pathogenicity/*physiology ; Candidiasis/*microbiology ; Humans ; Virulence ; Virulence Factors ; }, abstract = {Only few Candida species, e.g., Candida albicans, Candida glabrata, Candida dubliniensis, and Candida parapsilosis, are successful colonizers of a human host. Under certain circumstances these species can cause infections ranging from superficial to life-threatening disseminated candidiasis. The success of C. albicans, the most prevalent and best studied Candida species, as both commensal and human pathogen depends on its genetic, biochemical, and morphological flexibility which facilitates adaptation to a wide range of host niches. In addition, formation of biofilms provides additional protection from adverse environmental conditions. Furthermore, in many host niches Candida cells coexist with members of the human microbiome. The resulting fungal-bacterial interactions have a major influence on the success of C. albicans as commensal and also influence disease development and outcome. In this chapter, we review the current knowledge of important survival strategies of Candida spp., focusing on fundamental fitness and virulence traits of C. albicans.}, }
@article {pmid25907112, year = {2015}, author = {Bang, C and Schmitz, RA}, title = {Archaea associated with human surfaces: not to be underestimated.}, journal = {FEMS microbiology reviews}, volume = {39}, number = {5}, pages = {631-648}, doi = {10.1093/femsre/fuv010}, pmid = {25907112}, issn = {1574-6976}, mesh = {Archaea/classification/immunology/*physiology ; Humans ; Immune System/immunology/*microbiology ; Intestines/microbiology ; *Microbiota ; }, abstract = {Over 40 years ago, Carl Woese and his colleagues discovered the existence of two distinctly different groups of prokaryotes-Bacteria and Archaea. In the meantime, extensive research revealed that several hundred of bacterial species are intensely associated with humans' health and disease. Archaea, originally identified and described to occur mainly in extreme environments, have been shown to be ubiquitous and to appear frequently and in high numbers as part of human microbiota in recent years. Despite the improvement in methodologies leading to increased detection, archaea are often still not considered in many studies focusing on the interdependency between members of the microbiota and components of the human immune system. As a consequence, the knowledge on functional role(s) of archaeal species within the human body is mainly limited to their contribution to nutrient degradation in the intestine, and evidence for immunogenic properties of archaea as part of the human microbiota is generally rare. In this review, the current knowledge of human mucosa-associated archaeal species, their interaction with the human immune system and their potential contribution to humans' health and disease will be discussed.}, }
@article {pmid25888481, year = {2015}, author = {Wang, T and Mori, H and Zhang, C and Kurokawa, K and Xing, XH and Yamada, T}, title = {DomSign: a top-down annotation pipeline to enlarge enzyme space in the protein universe.}, journal = {BMC bioinformatics}, volume = {16}, number = {}, pages = {96}, pmid = {25888481}, issn = {1471-2105}, mesh = {Databases, Protein ; Enzymes/*chemistry ; Genome, Bacterial ; Humans ; Metagenomics ; Molecular Sequence Annotation/*methods ; Protein Structure, Tertiary ; Sequence Analysis, Protein ; *Software ; }, abstract = {BACKGROUND: Computational predictions of catalytic function are vital for in-depth understanding of enzymes. Because several novel approaches performing better than the common BLAST tool are rarely applied in research, we hypothesized that there is a large gap between the number of known annotated enzymes and the actual number in the protein universe, which significantly limits our ability to extract additional biologically relevant functional information from the available sequencing data. To reliably expand the enzyme space, we developed DomSign, a highly accurate domain signature-based enzyme functional prediction tool to assign Enzyme Commission (EC) digits.<br><br>RESULTS: DomSign is a top-down prediction engine that yields results comparable, or superior, to those from many benchmark EC number prediction tools, including BLASTP, when a homolog with an identity >30% is not available in the database. Performance tests showed that DomSign is a highly reliable enzyme EC number annotation tool. After multiple tests, the accuracy is thought to be greater than 90%. Thus, DomSign can be applied to large-scale datasets, with the goal of expanding the enzyme space with high fidelity. Using DomSign, we successfully increased the percentage of EC-tagged enzymes from 12% to 30% in UniProt-TrEMBL. In the Kyoto Encyclopedia of Genes and Genomes bacterial database, the percentage of EC-tagged enzymes for each bacterial genome could be increased from 26.0% to 33.2% on average. Metagenomic mining was also efficient, as exemplified by the application of DomSign to the Human Microbiome Project dataset, recovering nearly one million new EC-labeled enzymes.<br><br>CONCLUSIONS: Our results offer preliminarily confirmation of the existence of the hypothesized huge number of "hidden enzymes" in the protein universe, the identification of which could substantially further our understanding of the metabolisms of diverse organisms and also facilitate bioengineering by providing a richer enzyme resource. Furthermore, our results highlight the necessity of using more advanced computational tools than BLAST in protein database annotations to extract additional biologically relevant functional information from the available biological sequences.}, }
@article {pmid25887946, year = {2015}, author = {Gupta, VK and Chaudhari, NM and Iskepalli, S and Dutta, C}, title = {Divergences in gene repertoire among the reference Prevotella genomes derived from distinct body sites of human.}, journal = {BMC genomics}, volume = {16}, number = {1}, pages = {153}, pmid = {25887946}, issn = {1471-2164}, mesh = {Gastrointestinal Tract/microbiology ; *Genome, Bacterial ; Humans ; Metagenome ; Microbiota/*genetics ; Mouth/microbiology ; *Phylogeny ; Prevotella/*genetics ; Skin/microbiology ; Tissue Distribution ; Urogenital System/microbiology ; }, abstract = {BACKGROUND: The community composition of the human microbiome is known to vary at distinct anatomical niches. But little is known about the nature of variations, if any, at the genome/sub-genome levels of a specific microbial community across different niches. The present report aims to explore, as a case study, the variations in gene repertoire of 28 Prevotella reference genomes derived from different body-sites of human, as reported earlier by the Human Microbiome Consortium.<br><br>RESULTS: The pan-genome for Prevotella remains "open". On an average, 17% of predicted protein-coding genes of any particular Prevotella genome represent the conserved core genes, while the remaining 83% contribute to the flexible and singletons. The study reveals exclusive presence of 11798, 3673, 3348 and 934 gene families and exclusive absence of 17, 221, 115 and 645 gene families in Prevotella genomes derived from human oral cavity, gastro-intestinal tracts (GIT), urogenital tract (UGT) and skin, respectively. Distribution of various functional COG categories differs significantly among the habitat-specific genes. No niche-specific variations could be observed in distribution of KEGG pathways.<br><br>CONCLUSIONS: Prevotella genomes derived from different body sites differ appreciably in gene repertoire, suggesting that these microbiome components might have developed distinct genetic strategies for niche adaptation within the host. Each individual microbe might also have a component of its own genetic machinery for host adaptation, as appeared from the huge number of singletons.}, }
@article {pmid25885687, year = {2015}, author = {Manor, O and Borenstein, E}, title = {MUSiCC: a marker genes based framework for metagenomic normalization and accurate profiling of gene abundances in the microbiome.}, journal = {Genome biology}, volume = {16}, number = {1}, pages = {53}, pmid = {25885687}, issn = {1474-760X}, support = {DP2 AT007802/AT/NCCIH NIH HHS/United States ; P30 DK089507/DK/NIDDK NIH HHS/United States ; }, mesh = {Algorithms ; Cell Proliferation/genetics ; High-Throughput Nucleotide Sequencing/methods ; Humans ; Machine Learning ; *Metagenomics ; Microbiota/*genetics ; Sequence Analysis, DNA/*methods ; }, abstract = {Functional metagenomic analyses commonly involve a normalization step, where measured levels of genes or pathways are converted into relative abundances. Here, we demonstrate that this normalization scheme introduces marked biases both across and within human microbiome samples, and identify sample- and gene-specific properties that contribute to these biases. We introduce an alternative normalization paradigm, MUSiCC, which combines universal single-copy genes with machine learning methods to correct these biases and to obtain an accurate and biologically meaningful measure of gene abundances. Finally, we demonstrate that MUSiCC significantly improves downstream discovery of functional shifts in the microbiome.MUSiCC is available at http://elbo.gs.washington.edu/software.html .}, }
@article {pmid25883569, year = {2015}, author = {Braundmeier, AG and Lenz, KM and Inman, KS and Chia, N and Jeraldo, P and Walther-António, MR and Berg Miller, ME and Yang, F and Creedon, DJ and Nelson, H and White, BA}, title = {Individualized medicine and the microbiome in reproductive tract.}, journal = {Frontiers in physiology}, volume = {6}, number = {}, pages = {97}, pmid = {25883569}, issn = {1664-042X}, abstract = {Humans have evolved along with the millions of microorganisms that populate their bodies. These microbes (10(14)) outnumber human cells by 10 to 1 and account for 3 × 10(6) genes, more than ten times the 25,000 human genes. This microbial metagenome acts as our "other genome" and like our own genes, is unique to the individual. Recent international efforts such as the Human Microbiome Project (HMP) and the MetaHIT Project have helped catalog these microbial genomes using culture-independent, high-throughput, next-generation sequencing. This manuscript will describe recent efforts to define microbial diversity in the female reproductive tract because of the impact that microbial function has on reproductive efficiency. In this review, we will discuss current evidence that microbial communities are critical for maintaining reproductive health and how perturbations of microbial community structures can impact reproductive health from the aspect of infection, reproductive cyclicity, pregnancy, and disease states. Investigations of the human microbiome are propelling interventional strategies from treating medical populations to treating individual patients. In particular, we highlight how understanding and defining microbial community structures in different disease and physiological states have lead to the discovery of biomarkers and, more importantly, the development and implementation of microbial intervention strategies (probiotics) into modern day medicine. Finally this review will conclude with a literature summary of the effectiveness of microbial intervention strategies that have been implemented in animal and human models of disease and the potential for integrating these microbial intervention strategies into standard clinical practice.}, }
@article {pmid25864640, year = {2015}, author = {Sankar, SA and Lagier, JC and Pontarotti, P and Raoult, D and Fournier, PE}, title = {The human gut microbiome, a taxonomic conundrum.}, journal = {Systematic and applied microbiology}, volume = {38}, number = {4}, pages = {276-286}, doi = {10.1016/j.syapm.2015.03.004}, pmid = {25864640}, issn = {1618-0984}, mesh = {*Bacteria/classification/genetics ; Humans ; *Metagenome ; Metagenomics ; *Microbiota ; Phylogeny ; }, abstract = {From culture to metagenomics, within only 130 years, our knowledge of the human microbiome has considerably improved. With >1000 microbial species identified to date, the gastro-intestinal microbiota is the most complex of human biotas. It is composed of a majority of Bacteroidetes and Firmicutes and, although exhibiting great inter-individual variations according to age, geographic origin, disease or antibiotic uptake, it is stable over time. Metagenomic studies have suggested associations between specific gut microbiota compositions and a variety of diseases, including irritable bowel syndrome, Crohn's disease, colon cancer, type 2 diabetes and obesity. However, these data remain method-dependent, as no consensus strategy has been defined to decipher the complexity of the gut microbiota. High-throughput culture-independent techniques have highlighted the limitations of culture by showing the importance of uncultured species, whereas modern culture methods have demonstrated that metagenomics underestimates the microbial diversity by ignoring minor populations. In this review, we highlight the progress and challenges that pave the way to a complete understanding of the human gastrointestinal microbiota and its influence on human health.}, }
@article {pmid25853934, year = {2015}, author = {Nayfach, S and Pollard, KS}, title = {Average genome size estimation improves comparative metagenomics and sheds light on the functional ecology of the human microbiome.}, journal = {Genome biology}, volume = {16}, number = {1}, pages = {51}, pmid = {25853934}, issn = {1474-760X}, support = {T32 EB009383/EB/NIBIB NIH HHS/United States ; T32 GM067547/GM/NIGMS NIH HHS/United States ; }, mesh = {*Genome Size ; Genome, Bacterial ; Humans ; Metagenome/*genetics ; *Metagenomics ; Microbiota/*genetics ; Sequence Analysis, DNA ; }, abstract = {Average genome size is an important, yet often overlooked, property of microbial communities. We developed MicrobeCensus to rapidly and accurately estimate average genome size from shotgun metagenomic data and applied our tool to 1,352 human microbiome samples. We found that average genome size differs significantly within and between body sites and tracks with major functional and taxonomic differences. In the gut, average genome size is positively correlated with the abundance of Bacteroides and genes related to carbohydrate metabolism. Importantly, we found that average genome size variation can bias comparative analyses, and that normalization improves detection of differentially abundant genes.}, }
@article {pmid25852213, year = {2015}, author = {Rosenfeld, CS}, title = {Microbiome Disturbances and Autism Spectrum Disorders.}, journal = {Drug metabolism and disposition: the biological fate of chemicals}, volume = {43}, number = {10}, pages = {1557-1571}, doi = {10.1124/dmd.115.063826}, pmid = {25852213}, issn = {1521-009X}, mesh = {Animals ; Autism Spectrum Disorder/diet therapy/immunology/*microbiology ; Dysbiosis/diet therapy/immunology/*microbiology ; Gastrointestinal Microbiome/*physiology ; Gastrointestinal Tract/immunology/microbiology ; Humans ; Microbiota/physiology ; Prebiotics/administration &amp; dosage ; Probiotics/administration &amp; dosage ; }, abstract = {Autism spectrum disorders (ASDs) are considered a heterogenous set of neurobehavioral diseases, with the rates of diagnosis dramatically increasing in the past few decades. As genetics alone does not explain the underlying cause in many cases, attention has turned to environmental factors as potential etiological agents. Gastrointestinal disorders are a common comorbidity in ASD patients. It was thus hypothesized that a gut-brain link may account for some autistic cases. With the characterization of the human microbiome, this concept has been expanded to include the microbiota-gut-brain axis. There are mounting reports in animal models and human epidemiologic studies linking disruptive alterations in the gut microbiota or dysbiosis and ASD symptomology. In this review, we will explore the current evidence that gut dysbiosis in animal models and ASD patients correlates with disease risk and severity. The studies to date have surveyed how gut microbiome changes may affect these neurobehavioral disorders. However, we harbor other microbiomes in the body that might impact brain function. We will consider microbial colonies residing in the oral cavity, vagina, and the most recently discovered one in the placenta. Based on the premise that gut microbiota alterations may be causative agents in ASD, several therapeutic options have been tested, such as diet modulations, prebiotics, probiotics, synbiotics, postbiotics, antibiotics, fecal transplantation, and activated charcoal. The potential benefits of these therapies will be considered. Finally, the possible mechanisms by which changes in the gut bacterial communities may result in ASD and related neurobehavioral disorders will be examined.}, }
@article {pmid25842007, year = {2015}, author = {Imangaliyev, S and Keijser, B and Crielaard, W and Tsivtsivadze, E}, title = {Personalized microbial network inference via co-regularized spectral clustering.}, journal = {Methods (San Diego, Calif.)}, volume = {83}, number = {}, pages = {28-35}, doi = {10.1016/j.ymeth.2015.03.017}, pmid = {25842007}, issn = {1095-9130}, mesh = {Algorithms ; *Cluster Analysis ; Computational Biology/*methods ; Humans ; *Microbial Consortia ; Microbiota/*genetics ; }, abstract = {We use Human Microbiome Project (HMP) cohort (Peterson et al., 2009) to infer personalized oral microbial networks of healthy individuals. To determine clustering of individuals with similar microbial profiles, co-regularized spectral clustering algorithm is applied to the dataset. For each cluster we discovered, we compute co-occurrence relationships among the microbial species that determine microbial network per cluster of individuals. The results of our study suggest that there are several differences in microbial interactions on personalized network level in healthy oral samples acquired from various niches. Based on the results of co-regularized spectral clustering we discover two groups of individuals with different topology of their microbial interaction network. The results of microbial network inference suggest that niche-wise interactions are different in these two groups. Our study shows that healthy individuals have different microbial clusters according to their oral microbiota. Such personalized microbial networks open a better understanding of the microbial ecology of healthy oral cavities and new possibilities for future targeted medication. The scripts written in scientific Python and in Matlab, which were used for network visualization, are provided for download on the website http://learning-machines.com/.}, }
@article {pmid25825673, year = {2015}, author = {Weingarden, A and González, A and Vázquez-Baeza, Y and Weiss, S and Humphry, G and Berg-Lyons, D and Knights, D and Unno, T and Bobr, A and Kang, J and Khoruts, A and Knight, R and Sadowsky, MJ}, title = {Dynamic changes in short- and long-term bacterial composition following fecal microbiota transplantation for recurrent Clostridium difficile infection.}, journal = {Microbiome}, volume = {3}, number = {}, pages = {10}, pmid = {25825673}, issn = {2049-2618}, support = {R21 AI091907/AI/NIAID NIH HHS/United States ; UL1 TR000114/TR/NCATS NIH HHS/United States ; }, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) is an effective treatment for recurrent Clostridium difficile infection (CDI) that often fails standard antibiotic therapy. Despite its widespread recent use, however, little is known about the stability of the fecal microbiota following FMT.<br><br>RESULTS: Here we report on short- and long-term changes and provide kinetic visualization of fecal microbiota composition in patients with multiply recurrent CDI that were refractory to antibiotic therapy and treated using FMT. Fecal samples were collected from four patients before and up to 151 days after FMT, with daily collections until 28 days and weekly collections until 84 days post-FMT. The composition of fecal bacteria was characterized using high throughput 16S rRNA gene sequence analysis, compared to microbiota across body sites in the Human Microbiome Project (HMP) database, and visualized in a movie-like, kinetic format. FMT resulted in rapid normalization of bacterial fecal sample composition from a markedly dysbiotic state to one representative of normal fecal microbiota. While the microbiome appeared most similar to the donor implant material 1 day post-FMT, the composition diverged variably at later time points. The donor microbiota composition also varied over time. However, both post-FMT and donor samples remained within the larger cloud of fecal microbiota characterized as healthy by the HMP.<br><br>CONCLUSIONS: Dynamic behavior is an intrinsic property of normal fecal microbiota and should be accounted for in comparing microbial communities among normal individuals and those with disease states. This also suggests that more frequent sample analyses are needed in order to properly assess success of FMT procedures.}, }
@article {pmid25810247, year = {2015}, author = {Fishman, JA and Thomson, AW}, title = {Clinical Implications of Basic Science Discoveries: Immune Homeostasis and the Microbiome-Dietary and Therapeutic Modulation and Implications for Transplantation.}, journal = {American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons}, volume = {15}, number = {7}, pages = {1755-1758}, doi = {10.1111/ajt.13236}, pmid = {25810247}, issn = {1600-6143}, mesh = {Homeostasis/*physiology ; Humans ; Immune System/*immunology/metabolism/*microbiology ; Immune System Diseases/immunology/microbiology/*therapy ; Immunity, Innate ; Microbiota/*immunology ; *Organ Transplantation ; Probiotics/*therapeutic use ; }, abstract = {Links between the human microbiome and the innate and adaptive immune systems and their impact on autoimmune and inflammatory diseases are only beginning to be recognized. Characterization of the complex human microbial community is facilitated by culture-independent nucleic acid sequencing tools and bioinformatics systems. Specific organisms and microbial antigens are linked with initiation of innate immune responses that, depending on the context, may be associated with tolerogenic or effector immune responses. Further complexity is introduced by preclinical data that demonstrate the impacts of dietary manipulation on the prevention of genetically determined, systemic autoimmune disorders and on gastrointestinal microbiota. Investigation of interactions of complex microbial populations with the human immune system may provide new targets for clinical management in allotransplantation.}, }
@article {pmid25807083, year = {2015}, author = {Blount, ZD}, title = {The unexhausted potential of E. coli.}, journal = {eLife}, volume = {4}, number = {}, pages = {}, pmid = {25807083}, issn = {2050-084X}, mesh = {Animals ; *Biofilms ; Biological Evolution ; Environmental Microbiology ; Escherichia coli/*genetics/*physiology/ultrastructure ; Genomics/*methods ; Host-Pathogen Interactions ; Humans ; Intestines/*microbiology ; Microscopy, Electron, Scanning ; }, abstract = {E. coli's hardiness, versatility, broad palate and ease of handling have made it the most intensively studied and best understood organism on the planet. However, research on E.coli has primarily examined it as a model organism, one that is abstracted from any natural history. But E. coli is far more than just a microbial lab rat. Rather, it is a highly diverse organism with a complex, multi-faceted niche in the wild. Recent studies of 'wild' E. coli have, for example, revealed a great deal about its presence in the environment, its diversity and genomic evolution, as well as its role in the human microbiome and disease. These findings have shed light on aspects of its biology and ecology that pose far-reaching questions and illustrate how an appreciation of E. coli's natural history can expand its value as a model organism.}, }
@article {pmid25798435, year = {2015}, author = {Gritz, EC and Bhandari, V}, title = {The human neonatal gut microbiome: a brief review.}, journal = {Frontiers in pediatrics}, volume = {3}, number = {}, pages = {17}, pmid = {25798435}, issn = {2296-2360}, abstract = {The field of genomics has expanded into subspecialties such as metagenomics over the course of the last decade and a half. The development of massively parallel sequencing capabilities has allowed for increasingly detailed study of the genome of the human microbiome, the microbial super organ that resides symbiotically within the mucosal tissues and integumentary system of the human host. The gut microbiome, and particularly the study of its origins in neonates, has become subtopics of great interest within the field of genomics. This brief review seeks to summarize recent literature regarding the origins and establishment of the neonatal gut microbiome, beginning in utero, and how it is affected by neonatal nutritional status (breastfed versus formula fed) and gestational age (term versus preterm). We also explore the role of dysbiosis, a perturbation within the fragile ecosystem of the microbiome, and its role in the origin of select pathologic states, specifically, obesity and necrotizing enterocolitis (NEC) in preterm infants. We discuss the evidence supporting enteral pre- and pro-biotic supplementation of commensal organisms such as Bifidobacterium and Lactobacillus in the neonatal period, and their role in the prevention and amelioration of NEC in premature infants. Finally, we review directions to consider for further research to promote human health within this field.}, }
@article {pmid25797243, year = {2015}, author = {Mitsuhashi, K and Nosho, K and Sukawa, Y and Matsunaga, Y and Ito, M and Kurihara, H and Kanno, S and Igarashi, H and Naito, T and Adachi, Y and Tachibana, M and Tanuma, T and Maguchi, H and Shinohara, T and Hasegawa, T and Imamura, M and Kimura, Y and Hirata, K and Maruyama, R and Suzuki, H and Imai, K and Yamamoto, H and Shinomura, Y}, title = {Association of Fusobacterium species in pancreatic cancer tissues with molecular features and prognosis.}, journal = {Oncotarget}, volume = {6}, number = {9}, pages = {7209-7220}, pmid = {25797243}, issn = {1949-2553}, mesh = {Aged ; Biomarkers, Tumor/metabolism ; CpG Islands ; DNA Methylation ; Epigenesis, Genetic ; Female ; Fusobacterium/*pathogenicity ; Fusobacterium Infections/*complications ; Gene Expression Profiling ; Humans ; Kaplan-Meier Estimate ; Male ; Microsatellite Instability ; Middle Aged ; Multivariate Analysis ; Pancreatic Neoplasms/complications/genetics/*microbiology ; Phenotype ; Prognosis ; Proportional Hazards Models ; Regression Analysis ; Sequence Analysis, DNA ; Treatment Outcome ; }, abstract = {Recently, bacterial infection causing periodontal disease has attracted considerable attention as a risk factor for pancreatic cancer. Fusobacterium species is an oral bacterial group of the human microbiome. Some evidence suggests that Fusobacterium species promote colorectal cancer development; however, no previous studies have reported the association between Fusobacterium species and pancreatic cancer. Therefore, we examined whether Fusobacterium species exist in pancreatic cancer tissue. Using a database of 283 patients with pancreatic ductal adenocarcinoma (PDAC), we tested cancer tissue specimens for Fusobacterium species. We also tested the specimens for KRAS, NRAS, BRAF and PIK3CA mutations and measured microRNA-21 and microRNA-31. In addition, we assessed epigenetic alterations, including CpG island methylator phenotype (CIMP). Our data showed an 8.8% detection rate of Fusobacterium species in pancreatic cancers; however, tumor Fusobacterium status was not associated with any clinical and molecular features. In contrast, in multivariate Cox regression analysis, compared with the Fusobacterium species-negative group, we observed significantly higher cancer-specific mortality rates in the positive group (p = 0.023). In conclusion, Fusobacterium species were detected in pancreatic cancer tissue. Tumor Fusobacterium species status is independently associated with a worse prognosis of pancreatic cancer, suggesting that Fusobacterium species may be a prognostic biomarker of pancreatic cancer.}, }
@article {pmid25795652, year = {2015}, author = {Dietert, RR and Silbergeld, EK}, title = {Biomarkers for the 21st century: listening to the microbiome.}, journal = {Toxicological sciences : an official journal of the Society of Toxicology}, volume = {144}, number = {2}, pages = {208-216}, doi = {10.1093/toxsci/kfv013}, pmid = {25795652}, issn = {1096-0929}, mesh = {*Biomarkers ; Environmental Exposure ; Humans ; *Microbiota ; }, abstract = {The field of environmental research has benefited greatly from the concept of biomarkers, which originally expanded our thinking by opening the "black box" between environmental exposures and manifestations of disease and dysfunction in exposed populations, as laid out in a highly influential article published in 1987 by an expert committee convened by the National Research Council. Advances in biomedical research now challenge us to revise this concept to include the microbiome as a critical stage in the progression from exposure to outcome. Incorporating the microbiome into the basic 1987 model can spur new advances and understanding in environmental health. The human microbiome as a whole comprises the majority of cells and genes of the super-organism (host and microbiome). Site-specific microbiomes are the first to encounter xenobiotics, prior to absorption across gut, skin, or respiratory system. A growing literature indicates that these microbial communities may participate in biotransformation and thus constitute a compartment to add to the original biomarker schematic. In addition, these microbiomes interact with the "niche" in which they are located and thus transduce responses to and from the host organism. Incorporating the microbiome into the environmental health paradigm will enlarge our concepts of susceptibility as well as the interactions between xenobiotics and other factors that influence the status and function of these barrier systems. This article reviews the complexities of host:microbiome responses to xenobiotics in terms of redefining toxicokinetics and susceptibility. Our challenge is to consider these multiple interactions between and within the microbiome, the immune system, and other systems of the host in terms of exposure to exogenous agents, including environmental toxicants.}, }
@article {pmid25786791, year = {2015}, author = {Wisittipanit, N and Rangwala, H and Sikaroodi, M and Keshavarzian, A and Mutlu, EA and Gillevet, P}, title = {Classification methods for the analysis of LH-PCR data associated with inflammatory bowel disease patients.}, journal = {International journal of bioinformatics research and applications}, volume = {11}, number = {2}, pages = {111-129}, doi = {10.1504/IJBRA.2015.068087}, pmid = {25786791}, issn = {1744-5485}, support = {5R21DK071838-02/DK/NIDDK NIH HHS/United States ; }, mesh = {Algorithms ; Bacteria/*genetics/*isolation &amp; purification ; Humans ; Inflammatory Bowel Diseases/*microbiology ; Intestinal Mucosa/*microbiology ; Microbiota/genetics ; Pattern Recognition, Automated/*methods ; Polymerase Chain Reaction/*methods ; Reproducibility of Results ; Sensitivity and Specificity ; Support Vector Machine ; }, abstract = {The human gut is one of the most densely populated microbial communities in the world. The interaction of microbes with human host cells is responsible for several disease conditions and of criticality to human health. It is imperative to understand the relationships between these microbial communities within the human gut and their roles in disease. In this study we analyse the microbial communities within the human gut and their role in Inflammatory Bowel Disease (IBD). The bacterial communities were interrogated using Length Heterogeneity PCR (LH-PCR) fingerprinting of mucosal and luminal associated microbial communities for a class of healthy and diseases patients.}, }
@article {pmid25780927, year = {2015}, author = {De Spiegeleer, B and Verbeke, F and D'Hondt, M and Hendrix, A and Van De Wiele, C and Burvenich, C and Peremans, K and De Wever, O and Bracke, M and Wynendaele, E}, title = {The quorum sensing peptides PhrG, CSP and EDF promote angiogenesis and invasion of breast cancer cells in vitro.}, journal = {PloS one}, volume = {10}, number = {3}, pages = {e0119471}, pmid = {25780927}, issn = {1932-6203}, mesh = {Animals ; Bacterial Proteins/metabolism/physiology ; Breast Neoplasms/*pathology ; Caco-2 Cells ; Chick Embryo ; Female ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; Humans ; MCF-7 Cells ; Microbiota/*physiology ; *Neoplasm Invasiveness ; *Neovascularization, Pathologic ; *Quorum Sensing ; }, abstract = {The role of the human microbiome on cancer progression remains unclear. Therefore, in this study, we investigated the influence of some quorum sensing peptides, produced by diverse commensal or pathogenic bacteria, on breast cancer cell invasion and thus cancer outcome. Based on microscopy, transcriptome and Chick Chorioallantoic Membrane (CAM) analyses, four peptides (PhrG from B. subtilis, CSP from S. mitis and EDF from E. coli, together with its tripeptide analogue) were found to promote tumour cell invasion and angiogenesis, thereby potentially influencing tumour metastasis. Our results offer not only new insights on the possible role of the microbiome, but also further opportunities in cancer prevention and therapy by competing with these endogenous molecules and/or by modifying people's life style.}, }
@article {pmid25777787, year = {2015}, author = {Cope, EK and Lynch, SV}, title = {Novel microbiome-based therapeutics for chronic rhinosinusitis.}, journal = {Current allergy and asthma reports}, volume = {15}, number = {3}, pages = {504}, pmid = {25777787}, issn = {1534-6315}, mesh = {Animals ; Chronic Disease ; Homeostasis ; Humans ; *Microbiota ; Probiotics ; Rhinitis/drug therapy/*microbiology ; Sinusitis/drug therapy/*microbiology ; }, abstract = {The human microbiome, i.e. the collection of microbes that live on, in and interact with the human body, is extraordinarily diverse; microbiota have been detected in every tissue of the human body interrogated to date. Resident microbiota interact extensively with immune cells and epithelia at mucosal surfaces including the airways, and chronic inflammatory and allergic respiratory disorders are associated with dysbiosis of the airway microbiome. Chronic rhinosinusitis (CRS) is a heterogeneous disease with a large socioeconomic impact, and recent studies have shown that sinus inflammation is associated with decreased sinus bacterial diversity and the concomitant enrichment of specific sinus pathogens. Here, we discuss the potential role for probiotic supplementation for CRS in light of this increasing understanding of the airway microbiome and microbial interactions with the host. We focus on the ecological significance of microbiome-based probiotic supplementation and potential interactions with the gastrointestinal tract and consider microbial administration methods for treatment of CRS.}, }
@article {pmid25775922, year = {2015}, author = {Prince, AL and Chu, DM and Seferovic, MD and Antony, KM and Ma, J and Aagaard, KM}, title = {The perinatal microbiome and pregnancy: moving beyond the vaginal microbiome.}, journal = {Cold Spring Harbor perspectives in medicine}, volume = {5}, number = {6}, pages = {}, pmid = {25775922}, issn = {2157-1422}, support = {DP2 DP21DP2OD001500/OD/NIH HHS/United States ; T32GM007330/GM/NIGMS NIH HHS/United States ; DP2 OD001500/OD/NIH HHS/United States ; T32GM088129/GM/NIGMS NIH HHS/United States ; R01NR014792/NR/NINR NIH HHS/United States ; //Howard Hughes Medical Institute/United States ; R01 DK089201/DK/NIDDK NIH HHS/United States ; T32 GM007330/GM/NIGMS NIH HHS/United States ; R01 NR014792/NR/NINR NIH HHS/United States ; T32 GM088129/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; DNA, Bacterial/genetics ; Female ; Genome-Wide Association Study ; Humans ; Infant, Newborn ; Infectious Disease Transmission, Vertical ; Metagenomics/*methods ; Mice ; Microbiota/genetics/*physiology ; Placenta/microbiology ; Pregnancy ; Pregnancy Complications, Infectious/*microbiology ; Reproductive Health ; Vagina/*microbiology ; }, abstract = {The human microbiome, the collective genome of the microbial community that is on and within us, has recently been mapped. The initial characterization of healthy subjects has provided investigators with a reference population for interrogating the microbiome in metabolic, intestinal, and reproductive health and disease states. Although it is known that bacteria can colonize the vagina, recent metagenomic studies have shown that the vaginal microbiome varies among reproductive age women. Similarly, the richness and diversity of intestinal microbiota also naturally fluctuate among gravidae in both human and nonhuman primates, as well as mice. Moreover, recent evidence suggests that microbiome niches in pregnancy are not limited to maternal body sites, as the placenta appears to harbor a low biomass microbiome that is presumptively established in early pregnancy and varies in association with a remote history of maternal antenatal infection as well as preterm birth. In this article, we will provide a brief overview on metagenomics science as a means to investigate the microbiome, observations pertaining to both variation and the presumptive potential role of a varied microbiome during pregnancy, and how future studies of the microbiome in pregnancy may lend to a better understanding of human biology, reproductive health, and parturition.}, }
@article {pmid25774294, year = {2015}, author = {Hutter, T and Gimbert, C and Bouchard, F and Lapointe, FJ}, title = {Being human is a gut feeling.}, journal = {Microbiome}, volume = {3}, number = {}, pages = {9}, pmid = {25774294}, issn = {2049-2618}, abstract = {Some metagenomic studies have suggested that less than 10% of the cells that comprise our bodies are Homo sapiens cells. The remaining 90% are bacterial cells. The description of this so-called human microbiome is of great interest and importance for several reasons. For one, it helps us redefine what a biological individual is. We suggest that a human individual is now best described as a super-individual in which a large number of different species (including Homo sapiens) coexist. New concepts of biological individuality must extend beyond the traditional limitations of our own skin to include our resident microbes. Besides its important contributions to science, microbiome research raises philosophical questions that strike close to home. What is left of Homo sapiens? If most of our cells are not Homo sapiens cells, what does it mean to be an individual human being? In this paper, we argue that the biological individual is determined by the amount of functional integration among its constitutive parts, a definition that applies perfectly to Homo sapiens and its microbiome.}, }
@article {pmid25771098, year = {2015}, author = {Ruff, WE and Kriegel, MA}, title = {Autoimmune host-microbiota interactions at barrier sites and beyond.}, journal = {Trends in molecular medicine}, volume = {21}, number = {4}, pages = {233-244}, pmid = {25771098}, issn = {1471-499X}, support = {K08 AI095318/AI/NIAID NIH HHS/United States ; T32 AI007019/AI/NIAID NIH HHS/United States ; P30 DK079310/DK/NIDDK NIH HHS/United States ; P30 AR053495/AR/NIAMS NIH HHS/United States ; P30DK079310/DK/NIDDK NIH HHS/United States ; T32AI07019/AI/NIAID NIH HHS/United States ; }, mesh = {Adaptive Immunity ; Animals ; Autoimmune Diseases/immunology/*microbiology ; *Autoimmunity ; Disease Models, Animal ; Homeostasis ; Host-Pathogen Interactions/*immunology ; Humans ; Inflammatory Bowel Diseases/genetics/immunology ; Intestines/microbiology ; *Microbiota ; }, abstract = {The microbiota is considered to be an important factor influencing the pathogenesis of autoimmunity at both barrier sites and internal organs. Impinging on innate and adaptive immunity, commensals exert protective or detrimental effects on various autoimmune animal models. Human microbiome studies of autoimmunity remain largely descriptive, but suggest a role for dysbiosis in autoimmune disease. Humanized gnotobiotic approaches have advanced our understanding of immune-commensal interactions, but little is known about the mechanisms in autoimmunity. We propose that, similarly to infectious agents, the microbiota mediates autoimmunity via bystander activation, epitope spread, and, particularly under homeostatic conditions, via crossreactivity. This review presents an overview of the current literature concluding with outstanding questions in this field.}, }
@article {pmid25763184, year = {2015}, author = {Ross, MC and Muzny, DM and McCormick, JB and Gibbs, RA and Fisher-Hoch, SP and Petrosino, JF}, title = {16S gut community of the Cameron County Hispanic Cohort.}, journal = {Microbiome}, volume = {3}, number = {}, pages = {7}, pmid = {25763184}, issn = {2049-2618}, support = {P20 MD000170/MD/NIMHD NIH HHS/United States ; }, abstract = {BACKGROUND: Obesity and type 2 diabetes (T2D) are major public health concerns worldwide, and their prevalence has only increased in recent years. Mexican Americans are disproportionately afflicted by obesity and T2D, and rates are even higher in the United States-Mexico border region. To determine the factors associated with the increased risk of T2D, obesity, and other diseases in this population, the Cameron County Hispanic Cohort was established in 2004.<br><br>RESULTS: In this study, we characterized the 16S gut community of a subset of 63 subjects from this unique cohort. We found that these communities, when compared to Human Microbiome Project subjects, exhibit community shifts often observed in obese and T2D individuals in published studies. We also examined microbial network relationships between operational taxonomic units (OTUs) in the Cameron County Hispanic Cohort (CCHC) and three additional datasets. We identified a group of seven genera that form a tightly interconnected network present in all four tested datasets, dominated by butyrate producers, which are often increased in obese individuals while being depleted in T2D patients.<br><br>CONCLUSIONS: Through a combination of increased disease prevalence and relatively high gut microbial homogeneity in the subset of CCHC members we examined, we believe that the CCHC may represent an ideal community to dissect mechanisms underlying the role of the gut microbiome in human health and disease. The lack of CCHC subject gut community segregation based on all tested metadata suggests that the community structure we observe in the CCHC likely occurs early in life, and endures. This persistent 'disease'-related gut microbial community in CCHC subjects may enhance existing genetic or lifestyle predispositions to the prevalent diseases of the CCHC, leading to increased attack rates of obesity, T2D, non-alcoholic fatty liver disease, and others.}, }
@article {pmid25755571, year = {2014}, author = {Shalimar, }, title = {Gut microbiome and liver diseases.}, journal = {Journal of clinical and experimental hepatology}, volume = {4}, number = {3}, pages = {267-268}, pmid = {25755571}, issn = {0973-6883}, abstract = {Nan Qin(1,2), Fengling Yang(1), Ang Li(1), Edi Prifti(3), Yanfei Chen(1), Li Shao(1,2), Jing Guo(1), Emmanuelle Le Chatelier(3), Jian Yao(1,2), Lingjiao Wu(1), Jiawei Zhou(1), Shujun Ni(1), Lin Liu(1), Nicolas Pons(3), Jean Michel Batto(3), Sean P. Kennedy(3), Pierre Leonard(3), Chunhui Yuan(1), Wenchao Ding(1), Yuanting Chen(1), Xinjun Hu(1), Beiwen Zheng(1,2), Guirong Qian(1), Wei Xu(1), S. Dusko Ehrlich(3,4), Shusen Zheng(2,5) and Lanjuan Li(1,2) Alterations of the human gut microbiome in liver cirrhosis. Nature. 2014 Jul 23 [Epub ahead of print]. (1) State Key Laboratory for Diagnosis and Treatment of Infectious Disease, The First Affiliated Hospital, College of Medicine, Zhejiang University, 310003 Hangzhou, China; (2) Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Zhejiang University, 310003 Hangzhou, China; (3) Metagenopolis, Institut National de la Recherche Agronomique, 78350 Jouy en Josas, France; (4) King's College London, Centre for Host-Microbiome Interactions, Dental Institute Central Office, Guy's Hospital, London Bridge, London SE1 9RT, UK; (5) Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health, the First Affiliated Hospital, Zhejiang University, 310003 Hangzhou, China.}, }
@article {pmid25741335, year = {2015}, author = {Wagner Mackenzie, B and Waite, DW and Taylor, MW}, title = {Evaluating variation in human gut microbiota profiles due to DNA extraction method and inter-subject differences.}, journal = {Frontiers in microbiology}, volume = {6}, number = {}, pages = {130}, pmid = {25741335}, issn = {1664-302X}, abstract = {The human gut contains dense and diverse microbial communities which have profound influences on human health. Gaining meaningful insights into these communities requires provision of high quality microbial nucleic acids from human fecal samples, as well as an understanding of the sources of variation and their impacts on the experimental model. We present here a systematic analysis of commonly used microbial DNA extraction methods, and identify significant sources of variation. Five extraction methods (Human Microbiome Project protocol, MoBio PowerSoil DNA Isolation Kit, QIAamp DNA Stool Mini Kit, ZR Fecal DNA MiniPrep, phenol:chloroform-based DNA isolation) were evaluated based on the following criteria: DNA yield, quality and integrity, and microbial community structure based on Illumina amplicon sequencing of the V4 region of bacterial and archaeal 16S rRNA genes. Our results indicate that the largest portion of variation within the model was attributed to differences between subjects (biological variation), with a smaller proportion of variation associated with DNA extraction method (technical variation) and intra-subject variation. A comprehensive understanding of the potential impact of technical variation on the human gut microbiota will help limit preventable bias, enabling more accurate diversity estimates.}, }
@article {pmid25726633, year = {2014}, author = {Cojocaru, M and Chicoş, B}, title = {The human microbiome in autoimmune diseases.}, journal = {Romanian journal of internal medicine = Revue roumaine de medecine interne}, volume = {52}, number = {4}, pages = {285-288}, pmid = {25726633}, issn = {1220-4749}, mesh = {Autoimmune Diseases/*microbiology ; Gastrointestinal Tract/microbiology ; Humans ; *Microbiota ; }, abstract = {The human microbiome is the collection of all of the genes in all of the microbes in and on our bodies. Recently, the more appropriate term is "microbiota". There are numerous and complex relationships between the microbiome and our immune system. It is also becoming clear that if there is a disruption or disorganization in the microbiome community an inflammatory disease can occur.}, }
@article {pmid25714718, year = {2015}, author = {Newton, RJ and McLellan, SL and Dila, DK and Vineis, JH and Morrison, HG and Eren, AM and Sogin, ML}, title = {Sewage reflects the microbiomes of human populations.}, journal = {mBio}, volume = {6}, number = {2}, pages = {e02574}, pmid = {25714718}, issn = {2150-7511}, support = {R01 AI091829/AI/NIAID NIH HHS/United States ; R01AI091829-01A1/AI/NIAID NIH HHS/United States ; }, mesh = {*Biota ; Cities ; Cluster Analysis ; DNA, Bacterial/chemistry/genetics ; DNA, Ribosomal/chemistry/genetics ; Humans ; Molecular Sequence Data ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; Sewage/*microbiology ; United States ; }, abstract = {UNLABELLED: Molecular characterizations of the gut microbiome from individual human stool samples have identified community patterns that correlate with age, disease, diet, and other human characteristics, but resources for marker gene studies that consider microbiome trends among human populations scale with the number of individuals sampled from each population. As an alternative strategy for sampling populations, we examined whether sewage accurately reflects the microbial community of a mixture of stool samples. We used oligotyping of high-throughput 16S rRNA gene sequence data to compare the bacterial distribution in a stool data set to a sewage influent data set from 71 U.S. cities. On average, only 15% of sewage sample sequence reads were attributed to human fecal origin, but sewage recaptured most (97%) human fecal oligotypes. The most common oligotypes in stool matched the most common and abundant in sewage. After informatically separating sequences of human fecal origin, sewage samples exhibited ~3× greater diversity than stool samples. Comparisons among municipal sewage communities revealed the ubiquitous and abundant occurrence of 27 human fecal oligotypes, representing an apparent core set of organisms in U.S. populations. The fecal community variability among U.S. populations was significantly lower than among individuals. It clustered into three primary community structures distinguished by oligotypes from either: Bacteroidaceae, Prevotellaceae, or Lachnospiraceae/Ruminococcaceae. These distribution patterns reflected human population variation and predicted whether samples represented lean or obese populations with 81 to 89% accuracy. Our findings demonstrate that sewage represents the fecal microbial community of human populations and captures population-level traits of the human microbiome.<br><br>IMPORTANCE: The gut microbiota serves important functions in healthy humans. Numerous projects aim to define a healthy gut microbiome and its association with health states. However, financial considerations and privacy concerns limit the number of individuals who can be screened. By analyzing sewage from 71 cities, we demonstrate that geographically distributed U.S. populations share a small set of bacteria whose members represent various common community states within U.S. adults. Cities were differentiated by their sewage bacterial communities, and the community structures were good predictors of a city's estimated level of obesity. Our approach demonstrates the use of sewage as a means to sample the fecal microbiota from millions of people and its potential to elucidate microbiome patterns associated with human demographics.}, }
@article {pmid25714716, year = {2015}, author = {Vu, BG and Stach, CS and Kulhankova, K and Salgado-Pabón, W and Klingelhutz, AJ and Schlievert, PM}, title = {Chronic superantigen exposure induces systemic inflammation, elevated bloodstream endotoxin, and abnormal glucose tolerance in rabbits: possible role in diabetes.}, journal = {mBio}, volume = {6}, number = {2}, pages = {e02554}, pmid = {25714716}, issn = {2150-7511}, mesh = {Animals ; Bacterial Toxins/*blood ; Diabetes Mellitus, Type 2/*etiology/physiopathology ; Endotoxins/*blood ; Enterotoxins/*blood/metabolism ; Glucose Tolerance Test ; Inflammation/*pathology ; Rabbits ; Staphylococcal Infections/*complications ; Superantigens/*blood ; }, abstract = {UNLABELLED: Excessive weight and obesity are associated with the development of diabetes mellitus type 2 (DMII) in humans. They also pose high risks of Staphylococcus aureus colonization and overt infections. S. aureus causes a wide range of severe illnesses in both healthy and immunocompromised individuals. Among S. aureus virulence factors, superantigens are essential for pathogenicity. In this study, we show that rabbits that are chronically exposed to S. aureus superantigen toxic shock syndrome toxin-1 (TSST-1) experience impaired glucose tolerance, systemic inflammation, and elevated endotoxin levels in the bloodstream, all of which are common findings in DMII. Additionally, such DMII-associated findings are also seen through effects of TSST-1 on isolated adipocytes. Collectively, our findings suggest that chronic exposure to S. aureus superantigens facilitates the development of DMII, which may lead to therapeutic targeting of S. aureus and its superantigens.<br><br>IMPORTANCE: Obesity has a strong correlation with type 2 diabetes, in which fatty tissue, containing adipocytes, contributes to the development of the illness through altered metabolism and chronic inflammation. The human microbiome changes in persons with obesity and type 2 diabetes, including increases in Staphylococcus aureus colonization and overt infections. While the microbiome is essential for human wellness, there is little understanding of the role of microbes in obesity or the development of diabetes. Here, we demonstrate that the S.&#xa0;aureus superantigen toxic shock syndrome toxin-1 (TSST-1), an essential exotoxin in pathogenesis, induces inflammation, lipolysis, and insulin resistance in adipocytes both in vitro and in vivo. Chronic stimulation of rabbits with TSST-1 results in impaired systemic glucose tolerance, the hallmark finding in type 2 diabetes in humans, suggesting a role of S.&#xa0;aureus and its superantigens in the progression to type 2 diabetes.}, }
@article {pmid25702727, year = {2015}, author = {Walker, B and Kassim, K and Stokes, LD}, title = {The microbiome: a contributor to health and disease.}, journal = {Journal of health care for the poor and underserved}, volume = {26}, number = {1}, pages = {62-72}, doi = {10.1353/hpu.2015.0025}, pmid = {25702727}, issn = {1548-6869}, mesh = {Cardiovascular Diseases/microbiology ; Human Genome Project ; Humans ; Intestines/microbiology ; Irritable Bowel Syndrome/microbiology ; *Metagenome ; *Microbiota ; Neoplasms/microbiology ; Obesity/microbiology ; Renal Insufficiency, Chronic/microbiology ; }, abstract = {As the 21st century unfolds there is substantial evidence that biological research is experiencing extraordinary scientific and technological advances. Prominent among these advances are the completion of the Human Genome Project, which laid the foundation for the second advance, the Human Microbiome Project. Emerging from these advances are two overarching conclusions: a) genomics is no longer the sole domain of the geneticist, and b) we each are hosts to trillions of microorganisms. Genomics and other technologies have enhanced efforts to characterize the structure, composition, and functions of the microbiome. This characterization has fueled progress in understanding the role of the microbiome in health and disease. In this review, we highlight developments that have helped illuminate the microbiome-health connection. This information can improve an understanding of connections and relationships among multiple factors (or determinants) of health.}, }
@article {pmid25695334, year = {2015}, author = {Youmans, BP and Ajami, NJ and Jiang, ZD and Campbell, F and Wadsworth, WD and Petrosino, JF and DuPont, HL and Highlander, SK}, title = {Characterization of the human gut microbiome during travelers' diarrhea.}, journal = {Gut microbes}, volume = {6}, number = {2}, pages = {110-119}, pmid = {25695334}, issn = {1949-0984}, support = {F31 DK094596/DK/NIDDK NIH HHS/United States ; R21DK099573/DK/NIDDK NIH HHS/United States ; U54HG003273/HG/NHGRI NIH HHS/United States ; 2T32CA096520/CA/NCI NIH HHS/United States ; F31DK094596/DK/NIDDK NIH HHS/United States ; R25GM056929/GM/NIGMS NIH HHS/United States ; }, mesh = {Bacteria/*classification/genetics ; Caliciviridae Infections/*microbiology ; Diarrhea/*microbiology ; *Dysbiosis ; Escherichia coli Infections/*microbiology ; *Gastrointestinal Microbiome ; Humans ; *Travel ; }, abstract = {Alterations in the gut microbiota are correlated with ailments such as obesity, inflammatory bowel disease, and diarrhea. Up to 60% of individuals traveling from industrialized to developing countries acquire a form of secretory diarrhea known as travelers' diarrhea (TD), and enterotoxigenic Escherichia coli (ETEC) and norovirus (NoV) are the leading causative pathogens. Presumably, TD alters the gut microbiome, however the effect of TD on gut communities has not been studied. We report the first analysis of bacterial gut populations associated with TD. We examined and compared the gut microbiomes of individuals who developed TD associated with ETEC, NoV, or mixed pathogens, and TD with no pathogen identified, to healthy travelers. We observed a signature dysbiotic gut microbiome profile of high Firmicutes:Bacteroidetes ratios in the travelers who developed diarrhea, regardless of etiologic agent or presence of a pathogen. There was no significant difference in α-diversity among travelers. The bacterial composition of the microbiota of the healthy travelers was similar to the diarrheal groups, however the β-diversity of the healthy travelers was significantly different than any pathogen-associated TD group. Further comparison of the healthy traveler microbiota to those from healthy subjects who were part of the Human Microbiome Project also revealed a significantly higher Firmicutes:Bacteriodetes ratio in the healthy travelers and significantly different β-diversity. Thus, the composition of the gut microbiome in healthy, diarrhea-free travelers has characteristics of a dysbiotic gut, suggesting that these alterations could be associated with factors such as travel.}, }
@article {pmid25695131, year = {2015}, author = {Chernov, AV and Reyes, L and Xu, Z and Gonzalez, B and Golovko, G and Peterson, S and Perucho, M and Fofanov, Y and Strongin, AY}, title = {Mycoplasma CG- and GATC-specific DNA methyltransferases selectively and efficiently methylate the host genome and alter the epigenetic landscape in human cells.}, journal = {Epigenetics}, volume = {10}, number = {4}, pages = {303-318}, pmid = {25695131}, issn = {1559-2308}, support = {CA077470/CA/NCI NIH HHS/United States ; CA083017/CA/NCI NIH HHS/United States ; CA157328/CA/NCI NIH HHS/United States ; }, mesh = {Amino Acid Sequence ; Cell Line, Tumor ; Cell Nucleus/genetics ; Cell Proliferation ; Cloning, Molecular ; Colorectal Neoplasms/genetics/pathology ; CpG Islands ; DNA Modification Methylases/genetics/*metabolism ; *Epigenesis, Genetic ; Genetic Markers ; *Genome, Human ; Host-Pathogen Interactions ; Humans/parasitology ; Methylation ; Molecular Sequence Data ; Mycoplasma Infections/genetics ; Mycoplasma hyorhinis/*physiology ; }, abstract = {Aberrant DNA methylation is frequently observed in disease, including many cancer types, yet the underlying mechanisms remain unclear. Because germline and somatic mutations in the genes that are responsible for DNA methylation are infrequent in malignancies, additional mechanisms must be considered. Mycoplasmas spp., including Mycoplasma hyorhinis, efficiently colonize human cells and may serve as a vehicle for delivery of enzymatically active microbial proteins into the intracellular milieu. Here, we performed, for the first time, genome-wide and individual gene mapping of methylation marks generated by the M. hyorhinis CG- and GATC-specific DNA cytosine methyltransferases (MTases) in human cells. Our results demonstrated that, upon expression in human cells, MTases readily translocated to the cell nucleus. In the nucleus, MTases selectively and efficiently methylated the host genome at the DNA sequence sites free from pre-existing endogenous methylation, including those in a variety of cancer-associated genes. We also established that mycoplasma is widespread in colorectal cancers, suggesting that either the infection contributed to malignancy onset or, alternatively, that tumors provide a favorable environment for mycoplasma growth. In the human genome, ∼ 11% of GATC sites overlap with CGs (e.g., CGAT(m)CG); therefore, the methylated status of these sites can be perpetuated by human DNMT1. Based on these results, we now suggest that the GATC-specific methylation represents a novel type of infection-specific epigenetic mark that originates in human cells with a previous exposure to infection. Overall, our findings unveil an entirely new panorama of interactions between the human microbiome and epigenome with a potential impact in disease etiology.}, }
@article {pmid25691586, year = {2015}, author = {Shi, B and Chang, M and Martin, J and Mitreva, M and Lux, R and Klokkevold, P and Sodergren, E and Weinstock, GM and Haake, SK and Li, H}, title = {Dynamic changes in the subgingival microbiome and their potential for diagnosis and prognosis of periodontitis.}, journal = {mBio}, volume = {6}, number = {1}, pages = {e01926-14}, pmid = {25691586}, issn = {2150-7511}, support = {R01 DE021574/DE/NIDCR NIH HHS/United States ; RC1 DE020298/DE/NIDCR NIH HHS/United States ; }, mesh = {Adult ; *Biota ; Gingiva/*microbiology ; Humans ; Longitudinal Studies ; Metagenomics ; Middle Aged ; Periodontitis/*diagnosis/*microbiology ; Predictive Value of Tests ; Sequence Analysis, DNA ; Tooth Root/*microbiology ; }, abstract = {UNLABELLED: The human microbiome influences and reflects the health or disease state of the host. Periodontitis, a disease affecting about half of American adults, is associated with alterations in the subgingival microbiome of individual tooth sites. Although it can be treated, the disease can reoccur and may progress without symptoms. Without prognostic markers, follow-up examinations are required to assess reoccurrence and disease progression and to determine the need for additional treatments. To better identify and predict the disease progression, we aim to determine whether the subgingival microbiome can serve as a diagnosis and prognosis indicator. Using metagenomic shotgun sequencing, we characterized the dynamic changes in the subgingival microbiome in periodontitis patients before and after treatment at the same tooth sites. At the taxonomic composition level, the periodontitis-associated microorganisms were significantly shifted from highly correlated in the diseased state to poorly correlated after treatment, suggesting that coordinated interactions among the pathogenic microorganisms are essential to disease pathogenesis. At the functional level, we identified disease-associated pathways that were significantly altered in relative abundance in the two states. Furthermore, using the subgingival microbiome profile, we were able to classify the samples to their clinical states with an accuracy of 81.1%. Follow-up clinical examination of the sampled sites supported the predictive power of the microbiome profile on disease progression. Our study revealed the dynamic changes in the subgingival microbiome contributing to periodontitis and suggested potential clinical applications of monitoring the subgingival microbiome as an indicator in disease diagnosis and prognosis.<br><br>IMPORTANCE: Periodontitis is a common oral disease. Although it can be treated, the disease may reoccur without obvious symptoms. Current clinical examination parameters are useful in disease diagnosis but cannot adequately predict the outcome of individual tooth sites after treatment. A link between the subgingival microbiota and periodontitis was identified previously; however, it remains to be investigated whether the microbiome can serve as a diagnostic and prognostic indicator. In this study, for the first time, we characterized the subgingival microbiome of individual tooth sites before and after treatment using a large-scale metagenomic analysis. Our longitudinal study revealed changes in the microbiota in taxonomic composition, cooccurrence of subgingival microorganisms, and functional composition. Using the microbiome profiles, we were able to classify the clinical states of subgingival plaque samples with a high accuracy. Follow-up clinical examination of sampled sites indicates that the subgingival microbiome profile shows promise for the development of diagnostic and prognostic tools.}, }
@article {pmid25683180, year = {2015}, author = {Macovei, L and McCafferty, J and Chen, T and Teles, F and Hasturk, H and Paster, BJ and Campos-Neto, A}, title = {The hidden 'mycobacteriome' of the human healthy oral cavity and upper respiratory tract.}, journal = {Journal of oral microbiology}, volume = {7}, number = {}, pages = {26094}, pmid = {25683180}, issn = {2000-2297}, support = {R01 AI076425/AI/NIAID NIH HHS/United States ; R37 DE016937/DE/NIDCR NIH HHS/United States ; }, abstract = {The incidence of opportunistic non-tuberculous mycobacteria (NTM) infections has increased considerably in the past decades causing an array of infections, including respiratory and soft-tissue infections. NTM are ubiquitous and can be found in numerous environments, including households and water plants. However, NTM have not been reported to be associated with the healthy human oral microbiome. Since the oral cavity and upper respiratory track are the main ports of entry of microorganisms into the human body, elucidating NTM diversity and prevalence will assist in the assessment of the potential risks of infection elicited by these opportunistic pathogens. Here, we report the identification of a 'non-tuberculous mycobacteriome' in healthy individuals. We employed a modified DNA extraction procedure in conjunction with mycobacterial-specific primers to screen niches in the oral cavity (buccal mucosa and dental plaque) and upper respiratory tract (nostrils and oropharynx) of 10 healthy subjects. A total of 50 prevalent operational taxonomic units sequenced on MiSeq (Illumina) using 16S rRNA V3-V4 region were detected across all screened niches, showing the presence of diverse NTM communities. NTM DNA was detected in the nostrils of all 10 subjects, in buccal mucosa of 8 subjects, in the oropharynx of 7 subjects, and in the dental plaques of 5 subjects. Results from quantitative PCR showed each individual harbored 10(3)-10(4) predicted NTM per each screened niche. The modification of standard DNA isolation methods to increase sensitivity toward mycobacterial species represents an important step to advance the knowledge of the oral as well as the overall human microbiome. These findings clearly reveal for the first time that healthy individuals harbor a 'non-tuberculous mycobacteriome' in their oral cavity and upper respiratory tract and may have important implications in our understanding of infections caused by NTM.}, }
@article {pmid25682593, year = {2015}, author = {Muszer, M and Noszczyńska, M and Kasperkiewicz, K and Skurnik, M}, title = {Human Microbiome: When a Friend Becomes an Enemy.}, journal = {Archivum immunologiae et therapiae experimentalis}, volume = {63}, number = {4}, pages = {287-298}, pmid = {25682593}, issn = {1661-4917}, mesh = {Acne Vulgaris/microbiology ; Arthritis, Rheumatoid/microbiology ; Atherosclerosis/microbiology ; Autistic Disorder/microbiology ; Dermatitis, Atopic/microbiology ; Diabetes Mellitus, Type 1/microbiology ; Gastrointestinal Neoplasms/microbiology ; Homeostasis ; Humans ; Immune System ; Inflammatory Bowel Diseases/microbiology ; *Microbiota ; Multiple Sclerosis/microbiology ; Obesity/microbiology ; Psoriasis/microbiology ; Skin/immunology/microbiology ; }, abstract = {The microorganisms that inhabit humans are very diverse on different body sites and tracts. Each specific niche contains a unique composition of the microorganisms that are important for a balanced human physiology. Microbial cells outnumber human cells by tenfold and they function as an invisible organ that is called the microbiome. Excessive use of antibiotics and unhealthy diets pose a serious danger to the composition of the microbiome. An imbalance in the microbial community may cause pathological conditions of the digestive system such as obesity, cancer and inflammatory bowel disease; of the skin such as atopic dermatitis, psoriasis and acne and of the cardiovascular system such as atherosclerosis. An unbalanced microbiome has also been associated with neurodevelopmental disorders such as autism and multiple sclerosis. While the microbiome has a strong impact on the development of the host immune system, it is suspected that it can also be the cause of certain autoimmune diseases, including diabetes or rheumatoid arthritis. Despite the enormous progress in the field, the interactions between the human body and its microbiome still remain largely unknown. A better characterization of the interactions may allow for a deeper understanding of human disease states and help to elucidate a possible association between the composition of the microbiome and certain pathologies. This review focuses on general findings that are related to the area and provides no detailed information about the case of study. The aim is to give some initial insight on the studies of the microbiome and its connection with human health.}, }
@article {pmid25676470, year = {2015}, author = {Mayer, BT and Srinivasan, S and Fiedler, TL and Marrazzo, JM and Fredricks, DN and Schiffer, JT}, title = {Rapid and Profound Shifts in the Vaginal Microbiota Following Antibiotic Treatment for Bacterial Vaginosis.}, journal = {The Journal of infectious diseases}, volume = {212}, number = {5}, pages = {793-802}, pmid = {25676470}, issn = {1537-6613}, support = {R01 AI061628/AI/NIAID NIH HHS/United States ; U19 AI113173/AI/NIAID NIH HHS/United States ; S10 OD020069/OD/NIH HHS/United States ; K23 AI087206/AI/NIAID NIH HHS/United States ; U19 AI1131/AI/NIAID NIH HHS/United States ; }, mesh = {Anti-Bacterial Agents/*therapeutic use ; Bacteria/*drug effects/isolation &amp; purification ; Biota/*drug effects ; Female ; Humans ; Longitudinal Studies ; Metronidazole/*therapeutic use ; Models, Theoretical ; Time Factors ; Vagina/*microbiology ; Vaginosis, Bacterial/*drug therapy ; }, abstract = {BACKGROUND: Bacterial vaginosis (BV) is a common polymicrobial disease associated with numerous negative reproductive health outcomes, including an increased risk of human immunodeficiency virus acquisition. BV is treatable with antibiotics, but relapse is common. A more detailed understanding of bacterial dynamics during antibiotic therapy for BV could identify conditions that favor establishment, maintenance, and eradication of BV-associated bacterial species, thereby improving treatment outcomes.<br><br>METHODS: We used mathematical models to analyze daily quantitative measurements of 11 key bacterial species during metronidazole treatment for 15 cases of BV.<br><br>RESULTS: We identified complete reorganization of vaginal bacterial composition within a day of initiating therapy. Although baseline bacterial levels predicted a longer time to clearance, all anaerobic species were eliminated rapidly within a median of 3 days. However, reemergence of BV-associated species was common following treatment cessation. Gardnerella vaginalis, a facultative anaerobe, was cleared more slowly than anaerobic BV-associated species, and levels of G. vaginalis often rebounded during treatment. We observed gradual Lactobacillus species growth, indicating that untargeted microbes fill the transient vacuum formed during treatment.<br><br>CONCLUSIONS: Under antibiotic pressure, the human microbiome can undergo rapid shifts on a scale of hours. When treatment is stopped, BV-associated bacteria quickly reemerge, suggesting a possible role for intermittent prophylactic treatment.}, }
@article {pmid25675851, year = {2015}, author = {Jung, WH and Croll, D and Cho, JH and Kim, YR and Lee, YW}, title = {Analysis of the nasal vestibule mycobiome in patients with allergic rhinitis.}, journal = {Mycoses}, volume = {58}, number = {3}, pages = {167-172}, doi = {10.1111/myc.12296}, pmid = {25675851}, issn = {1439-0507}, mesh = {Adult ; Animals ; Female ; Fungi/*classification/genetics ; Genetic Variation ; Humans ; Malassezia/*classification ; Male ; Microbial Consortia ; *Microbiota ; Nose/*microbiology ; Paranasal Sinuses/*microbiology ; Phylogeny ; Rhinitis, Allergic/*microbiology ; Sequence Analysis, DNA ; Young Adult ; }, abstract = {Advances in culture-independent sequencing methods have been utilised in recent studies to understand the phylogenetic composition of the human microbiome of healthy and diseased skin. Allergic rhinitis (AR) is an inflammatory condition of the nasal cavity caused by environmental allergens. Although nasal microbial communities have been considered important contributors in human health, no studies to date have comprehensively compared fungal communities (mycobiome) of the nasal vestibule using the culture-independent pyrosequencing method. This study aimed to investigate how fungal communities of the nasal vestibule skin surface are influenced by AR. The phylogenetic composition of the nasal vestibule mycobiome of patients with AR was analysed by culture-independent pyrosequencing methods and compared with healthy individuals. A total of 69 fungal genera were identified from both AR samples and healthy controls, and the genus Malassezia predominated in the nasal vestibule. Species-level analysis classified eight different Malassezia species including M. pachydermatis and M. cuniculi, which were normally isolated from animals, and revealed M. restricta to be the most abundant species in the nasal vestibule. Although high interpersonal variation was observed, some of the AR samples displayed significantly higher diversities than healthy controls at both the genus and species level.}, }
@article {pmid25671105, year = {2014}, author = {Hanshew, AS and Jetté, ME and Thibeault, SL}, title = {Characterization and comparison of bacterial communities in benign vocal fold lesions.}, journal = {Microbiome}, volume = {2}, number = {}, pages = {43}, pmid = {25671105}, issn = {2049-2618}, support = {R01 DC009600/DC/NIDCD NIH HHS/United States ; T32 DC009401/DC/NIDCD NIH HHS/United States ; }, abstract = {BACKGROUND: Benign vocal fold lesions, including cysts, nodules, polyps, and Reinke's edema, are common causes of hoarseness and subsequent voice disorders. Given the prevalence of these lesions, disease etiology and pathophysiology remain unclear and their microbiota has not been studied to date secondary to the paucity of available biopsies for investigation. We sought to characterize and compare the bacterial communities in biopsies of cysts, nodules, polyps, and Reinke's edema collected from patients in Germany and Wisconsin. These samples were then compared to the communities found in healthy saliva and throat samples from the Human Microbiome Project (HMP).<br><br>RESULTS: 454 pyrosequencing of the V3-V5 regions of the 16S rRNA gene revealed five phyla that explained most of the bacterial diversity, including Firmicutes (73.8%), Proteobacteria (12.7%), Bacteroidetes (9.2%), Actinobacteria (2.1%), and Fusobacteria (1.9%). Every lesion sample, regardless of diagnosis, had operational taxonomic units (OTUs) identified as Streptococcus, with a mean abundance of 68.7%. Most of the lesions, 31 out of 44, were indistinguishable in a principal coordinates analysis (PCoA) due to dominance by OTUs phylogenetically similar to Streptococcus pseudopneumoniae. Thirteen lesions not dominated by S. pseudopneumoniae were more similar to HMP throat and saliva samples, though 12 of them contained Pseudomonas, which was not present in any of the HMP samples. Community structure and abundance could not be correlated with lesion diagnosis or any other documented patient factor, including age, sex, or country of origin.<br><br>CONCLUSIONS: Dominance by S. pseudopneumoniae could be a factor in disease etiology, as could the presence of Pseudomonas in some samples. Likewise, decreased diversity, as compared to healthy saliva and throat samples, may be associated with disease, similar to disease models in other mucosal sites.}, }
@article {pmid25667584, year = {2015}, author = {Santiago-Rodriguez, TM and Ly, M and Bonilla, N and Pride, DT}, title = {The human urine virome in association with urinary tract infections.}, journal = {Frontiers in microbiology}, volume = {6}, number = {}, pages = {14}, pmid = {25667584}, issn = {1664-302X}, abstract = {While once believed to represent a sterile environment, the human urinary tract harbors a unique cellular microbiota. We sought to determine whether the human urinary tract also is home to viral communities whose membership might reflect urinary tract health status. We recruited and sampled urine from 20 subjects, 10 subjects with urinary tract infections (UTIs) and 10 without UTIs, and found viral communities in the urine of each subject group. Most of the identifiable viruses were bacteriophage, but eukaryotic viruses also were identified in all subjects. We found reads from human papillomaviruses (HPVs) in 95% of the subjects studied, but none were found to be high-risk genotypes that are associated with cervical and rectal cancers. We verified the presence of some HPV genotypes by quantitative PCR. Some of the HPV genotypes identified were homologous to relatively novel and uncharacterized viruses that previously have been detected on skin in association with cancerous lesions, while others may be associated with anal and genital warts. On a community level, there was no association between the membership or diversity of viral communities based on urinary tract health status. While more data are still needed, detection of HPVs as members of the human urinary virome using viral metagenomics represents a non-invasive technique that could augment current screening techniques to detect low-risk HPVs in the genitourinary tracts of humans.}, }
@article {pmid25665875, year = {2015}, author = {Berg, D and Clemente, JC and Colombel, JF}, title = {Can inflammatory bowel disease be permanently treated with short-term interventions on the microbiome?.}, journal = {Expert review of gastroenterology &amp; hepatology}, volume = {9}, number = {6}, pages = {781-795}, doi = {10.1586/17474124.2015.1013031}, pmid = {25665875}, issn = {1747-4132}, mesh = {Anti-Bacterial Agents/adverse effects/*therapeutic use ; Colitis, Ulcerative/diagnosis/diet therapy/microbiology/*therapy ; Crohn Disease/diagnosis/diet therapy/microbiology/*therapy ; *Fecal Microbiota Transplantation/adverse effects ; Humans ; Intestines/*microbiology ; *Microbiota ; Probiotics/adverse effects/*therapeutic use ; Recurrence ; Remission Induction ; Time Factors ; Treatment Outcome ; }, abstract = {Inflammatory bowel disease, which includes Crohn's disease and ulcerative colitis, is a chronic, relapsing and remitting set of conditions characterized by an excessive inflammatory response leading to the destruction of the gastrointestinal tract. While the exact etiology of inflammatory bowel disease remains unclear, increasing evidence suggests that the human gastrointestinal microbiome plays a critical role in disease pathogenesis. Manipulation of the gut microbiome has therefore emerged as an attractive alternative for both prophylactic and therapeutic intervention against inflammation. Despite its growing popularity among patients, review of the current literature suggests that the adult microbiome is a highly stable structure resilient to short-term interventions. In fact, most evidence to date demonstrates that therapeutic agents targeting the microflora trigger rapid changes in the microbiome, which then reverts to its pre-treatment state once the therapy is completed. Based on these findings, our ability to treat inflammatory bowel disease through short-term manipulations of the human microbiome may only have a transient effect. Thus, this review is intended to highlight the use of various therapeutic options, including diet, pre- and probiotics, antibiotics and fecal microbiota transplant, to manipulate the microbiome, with specific attention to the alterations made to the microflora along with the duration of impact.}, }
@article {pmid25663180, year = {2015}, author = {Manasson, J and Scher, JU}, title = {Spondyloarthritis and the microbiome: new insights from an ancient hypothesis.}, journal = {Current rheumatology reports}, volume = {17}, number = {2}, pages = {10}, pmid = {25663180}, issn = {1534-6307}, support = {K23 AR064318/AR/NIAMS NIH HHS/United States ; K23AR064318/AR/NIAMS NIH HHS/United States ; }, mesh = {Arthritis, Psoriatic/microbiology ; Arthritis, Reactive/immunology ; Humans ; *Microbiota ; Prohibitins ; Spondylarthritis/*microbiology ; Spondylitis, Ankylosing/microbiology ; }, abstract = {The human microbiome, which represents the total collection of microorganisms (and their genes) inhabiting the human body, has increasingly been recognized as a potential key factor in the development of autoimmune disease. Multiple studies suggest that the microbiome has significant influence on immune homeostasis, while disruptions in local microbiome composition can result in a heightened systemic inflammatory response. The intestinal microbiome, in particular, harbors the densest assembly of bacteria and appears to influence the immune system in the context of inflammatory arthropathies. Although studies are still sparse, this review will examine the role of the microbiome in the pathogenesis of spondyloarthritis (SpA), particularly in enteropathic arthritis (EA), reactive arthritis (ReA), ankylosing spondylitis (AS), and psoriatic arthritis (PsA).}, }
@article {pmid25653214, year = {2015}, author = {Mao, B and Li, D and Zhao, J and Liu, X and Gu, Z and Chen, YQ and Zhang, H and Chen, W}, title = {In vitro fermentation of fructooligosaccharides with human gut bacteria.}, journal = {Food &amp; function}, volume = {6}, number = {3}, pages = {947-954}, doi = {10.1039/c4fo01082e}, pmid = {25653214}, issn = {2042-650X}, mesh = {Adult ; Bacterial Proteins/chemistry/genetics/metabolism ; Carrier Proteins/chemistry/genetics/metabolism ; China ; Clostridiales/classification/growth &amp; development/isolation &amp; purification/metabolism ; Cronobacter sakazakii/classification/growth &amp; development/isolation &amp; purification/metabolism ; Databases, Genetic ; Feces/microbiology ; Fermentation ; *Gastrointestinal Microbiome ; Glycoside Hydrolases/chemistry/genetics/metabolism ; Humans ; *Models, Biological ; Molecular Typing ; Oligosaccharides/adverse effects/*metabolism ; Open Reading Frames ; *Prebiotics/adverse effects ; Ruminococcus/classification/growth &amp; development/isolation &amp; purification/metabolism ; Sequence Alignment ; Weissella/classification/growth &amp; development/isolation &amp; purification/metabolism ; }, abstract = {Fructooligosaccharides (FOS) are one of the most studied prebiotics, selectively stimulating the growth of health-promoting bacteria in the host. However, there is increasing evidence that commensal gut bacteria, such as Bacteroides fragilis, Clostridium butyricum, Enterobacter cloacae, and even the pathogenic Escherichia coli BEN2908, are also able to metabolize FOS in vitro, and in some cases, FOS displayed adverse effects. Therefore, it is necessary to identify FOS-metabolizing species that are present in the gut. Unlike previous studies focusing on individual strains, this study used the traditional culture method combined with an alignment search on the gut bacteria database established from the Human Microbiome Project (HMP). The alignment results showed that homologous proteins for FOS transporters and glycosidases were distributed in 237 of the 453 strains of gut bacteria. La506 msmK encoding the ATP-binding protein and Aec45 fosGH1 encoding glycoside hydrolase were most widely distributed, in 155 and 55 strains, respectively. Seven of eight strains with both transporters and glycosidases were proven to be capable of metabolizing FOS, while five strains without either transporters or glycosidases were not. Fifteen species isolated from human feces and 11 species from the alignment search were identified to be FOS-metabolizing, of which Cronobacter sakazakii, Marvinbryantia formatexigens, Ruminococcus gnavus, and Weissella paramesenteroides are reported here for the first time. Thus, alignment search combined with the culture method is an effective method for obtaining a global view of the FOS-metabolizing bacteria in the gut and will be helpful in further investigating the relationship between FOS and human gut bacteria.}, }
@article {pmid25646566, year = {2015}, author = {Ford, CB and Funt, JM and Abbey, D and Issi, L and Guiducci, C and Martinez, DA and Delorey, T and Li, BY and White, TC and Cuomo, C and Rao, RP and Berman, J and Thompson, DA and Regev, A}, title = {The evolution of drug resistance in clinical isolates of Candida albicans.}, journal = {eLife}, volume = {4}, number = {}, pages = {e00662}, pmid = {25646566}, issn = {2050-084X}, support = {R01 CA119176/CA/NCI NIH HHS/United States ; DP1 CA174427/CA/NCI NIH HHS/United States ; //Howard Hughes Medical Institute/United States ; 2R01CA119176-01/CA/NCI NIH HHS/United States ; 8DP1CA174427/CA/NCI NIH HHS/United States ; }, mesh = {Adhesiveness ; Aneuploidy ; Candida albicans/*drug effects/*genetics/isolation &amp; purification ; Candidiasis/*microbiology ; Drug Resistance, Fungal/*drug effects/*genetics ; *Evolution, Molecular ; Fluconazole/pharmacology ; Genetic Fitness/drug effects ; Genome, Human ; Host-Pathogen Interactions/drug effects/genetics ; Humans ; Loss of Heterozygosity/genetics ; Microbial Sensitivity Tests ; Mutation/genetics ; Phenotype ; Polymorphism, Single Nucleotide/genetics ; Sequence Analysis, DNA ; Virulence/drug effects/genetics ; }, abstract = {Candida albicans is both a member of the healthy human microbiome and a major pathogen in immunocompromised individuals. Infections are typically treated with azole inhibitors of ergosterol biosynthesis often leading to drug resistance. Studies in clinical isolates have implicated multiple mechanisms in resistance, but have focused on large-scale aberrations or candidate genes, and do not comprehensively chart the genetic basis of adaptation. Here, we leveraged next-generation sequencing to analyze 43 isolates from 11 oral candidiasis patients. We detected newly selected mutations, including single-nucleotide polymorphisms (SNPs), copy-number variations and loss-of-heterozygosity (LOH) events. LOH events were commonly associated with acquired resistance, and SNPs in 240 genes may be related to host adaptation. Conversely, most aneuploidies were transient and did not correlate with drug resistance. Our analysis also shows that isolates also varied in adherence, filamentation, and virulence. Our work reveals new molecular mechanisms underlying the evolution of drug resistance and host adaptation.}, }
@article {pmid25642449, year = {2014}, author = {Sun, J and Chang, EB}, title = {Exploring gut microbes in human health and disease: Pushing the envelope.}, journal = {Genes &amp; diseases}, volume = {1}, number = {2}, pages = {132-139}, pmid = {25642449}, issn = {2352-4820}, support = {UL1 TR000430/TR/NCATS NIH HHS/United States ; P30 DK042086/DK/NIDDK NIH HHS/United States ; R03 DK089010/DK/NIDDK NIH HHS/United States ; R37 DK047722/DK/NIDDK NIH HHS/United States ; R01 DK097268/DK/NIDDK NIH HHS/United States ; R01 DK047722/DK/NIDDK NIH HHS/United States ; }, abstract = {Humans have coevolved with their microbes over thousands of years, but this relationship, is now being dramatically affected by shifts in the collective human microbiome resulting from changes in the environment and societal norms. Resulting perturbations of intestinal host-microbe interactions can lead to miscues and altered host responses that increase the risk of pathogenic processes and promote "western" disorders such as inflammatory bowel diseases, cancers, obesity, diabetes, autism, and asthma. Given the current challenges and limitations in gene therapy, approaches that can reshape the gut microbiome represent a reasonable strategy for restoring the balance between host and microbes. In this review and commentary, we highlight recent progress in our understanding of the intestinal microbiome in the context of health and diseases, focusing on mechanistic concepts that underlie the complex relationships between host and microbes. Despite these gains, many challenges lie ahead that make it difficult to close the gap between the basic sciences and clinical application. We will discuss the potential therapeutic strategies that can be used to manipulate the gut microbiota, recognizing that the promise of pharmabiotics ("bugs to drugs") is unlikely to be completely fulfilled without a greater understanding of enteric microbiota and its impact on mammalian physiology. By leveraging the knowledge gained through these studies, we will be prepared to enter the era of personalized medicine where clinical inventions can be custom-tailored to individual patients to achieve better outcomes.}, }
@article {pmid25636313, year = {2015}, author = {Cottier, F and Tan, AS and Chen, J and Lum, J and Zolezzi, F and Poidinger, M and Pavelka, N}, title = {The transcriptional stress response of Candida albicans to weak organic acids.}, journal = {G3 (Bethesda, Md.)}, volume = {5}, number = {4}, pages = {497-505}, pmid = {25636313}, issn = {2160-1836}, mesh = {Acids, Acyclic/*pharmacology ; Candida albicans/drug effects/genetics/metabolism ; Down-Regulation/drug effects ; Iron/metabolism ; Lactic Acid/*pharmacology ; RNA/biosynthesis ; RNA, Ribosomal/metabolism ; Transcriptome/*drug effects ; Up-Regulation/drug effects ; }, abstract = {Candida albicans is the most important fungal pathogen of humans, causing severe infections, especially in nosocomial and immunocompromised settings. However, it is also the most prevalent fungus of the normal human microbiome, where it shares its habitat with hundreds of trillions of other microbial cells. Despite weak organic acids (WOAs) being among the most abundant metabolites produced by bacterial microbiota, little is known about their effect on C. albicans. Here we used a sequencing-based profiling strategy to systematically investigate the transcriptional stress response of C. albicans to lactic, acetic, propionic, and butyric acid at several time points after treatment. Our data reveal a complex transcriptional response, with individual WOAs triggering unique gene expression profiles and with important differences between acute and chronic exposure. Despite these dissimilarities, we found significant overlaps between the gene expression changes induced by each WOA, which led us to uncover a core transcriptional response that was largely unrelated to other previously published C. albicans transcriptional stress responses. Genes commonly up-regulated by WOAs were enriched in several iron transporters, which was associated with an overall decrease in intracellular iron concentrations. Moreover, chronic exposure to any WOA lead to down-regulation of RNA synthesis and ribosome biogenesis genes, which resulted in significant reduction of total RNA levels and of ribosomal RNA in particular. In conclusion, this study suggests that gastrointestinal microbiota might directly influence C. albicans physiology via production of WOAs, with possible implications of how this fungus interacts with its host in both health and disease.}, }
@article {pmid25633721, year = {2015}, author = {Volz, T and Kaesler, S and Skabytska, Y and Biedermann, T}, title = {[The role of the innate immune system in atopic dermatitis].}, journal = {Der Hautarzt; Zeitschrift fur Dermatologie, Venerologie, und verwandte Gebiete}, volume = {66}, number = {2}, pages = {90-95}, pmid = {25633721}, issn = {1432-1173}, mesh = {Adaptive Immunity/*immunology ; Cytokines/*immunology ; Dermatitis, Atopic/*immunology ; Humans ; Immunity, Innate/*immunology ; Immunologic Factors/*immunology ; Models, Immunological ; Skin/*immunology ; }, abstract = {The mechanisms how the innate immune system detects microbes and mounts a rapid immune response have been more and more elucidated in the past years. Subsequently it has been shown that innate immunity also shapes adaptive immune responses and determines their quality that can be either inflammatory or tolerogenic. As atopic dermatitis is characterized by disturbances of innate and adaptive immune responses, colonization with pathogens and defects in skin barrier function, insight into mechanisms of innate immunity has helped to understand the vicious circle of ongoing skin inflammation seen in atopic dermatitis patients. Elucidating general mechanisms of the innate immune system and its functions in atopic dermatitis paves the way for developing new therapies. Especially the novel insights into the human microbiome and potential functional consequences make the innate immune system a very fundamental and promising target. As a result atopic dermatitis manifestations can be attenuated or even resolved. These currently developed strategies will be introduced in the current review.}, }
@article {pmid25630378, year = {2015}, author = {Zhbannikov, IY and Foster, JA}, title = {MetAmp: combining amplicon data from multiple markers for OTU analysis.}, journal = {Bioinformatics (Oxford, England)}, volume = {31}, number = {11}, pages = {1830-1832}, pmid = {25630378}, issn = {1367-4811}, support = {F31 GM016448/GM/NIGMS NIH HHS/United States ; P20 GM103408/GM/NIGMS NIH HHS/United States ; P20GM016454/GM/NIGMS NIH HHS/United States ; P20GM16448/GM/NIGMS NIH HHS/United States ; }, mesh = {Algorithms ; Classification/methods ; Genetic Markers ; Humans ; Metagenomics/*methods ; Microbiota ; RNA, Ribosomal, 16S/genetics ; *Software ; }, abstract = {MOTIVATION: We present a novel method and corresponding application, MetAmp, to combine amplicon data from multiple genomic markers into Operational Taxonomic Units (OTUs) for microbial community analysis, calibrating the markers using data from known microbial genomes. When amplicons for multiple markers such as the 16S rRNA gene hypervariable regions are available, MetAmp improves the accuracy of OTU-based methods for characterizing bacterial composition and community structure. MetAmp works best with at least three markers, and is applicable to non-bacterial analyses and to non 16S markers. Our application and testing have been limited to 16S analysis of microbial communities.<br><br>RESULTS: We clustered standard test sequences derived from the Human Microbiome Mock Community test sets and compared MetAmp and other tools with respect to their ability to recover OTUs for these benchmark bacterial communities. MetAmp compared favorably to QIIME, UPARSE and Mothur using amplicons from one, two, and three markers.<br><br>MetAmp is available at http://izhbannikov.github.io/MetAmp/.}, }
@article {pmid25621279, year = {2014}, author = {Thompson, JR and Rivera, HE and Closek, CJ and Medina, M}, title = {Microbes in the coral holobiont: partners through evolution, development, and ecological interactions.}, journal = {Frontiers in cellular and infection microbiology}, volume = {4}, number = {}, pages = {176}, pmid = {25621279}, issn = {2235-2988}, mesh = {Animals ; Anthozoa/genetics/*microbiology ; Bacteria/classification/genetics/isolation &amp; purification ; *Bacterial Physiological Phenomena ; *Biological Evolution ; *Ecosystem ; Symbiosis ; }, abstract = {In the last two decades, genetic and genomic studies have revealed the astonishing diversity and ubiquity of microorganisms. Emergence and expansion of the human microbiome project has reshaped our thinking about how microbes control host health-not only as pathogens, but also as symbionts. In coral reef environments, scientists have begun to examine the role that microorganisms play in coral life history. Herein, we review the current literature on coral-microbe interactions within the context of their role in evolution, development, and ecology. We ask the following questions, first posed by McFall-Ngai et al. (2013) in their review of animal evolution, with specific attention to how coral-microbial interactions may be affected under future environmental conditions: (1) How do corals and their microbiome affect each other's genomes? (2) How does coral development depend on microbial partners? (3) How is homeostasis maintained between corals and their microbial symbionts? (4) How can ecological approaches deepen our understanding of the multiple levels of coral-microbial interactions? Elucidating the role that microorganisms play in the structure and function of the holobiont is essential for understanding how corals maintain homeostasis and acclimate to changing environmental conditions.}, }
@article {pmid25601913, year = {2014}, author = {Goedert, JJ and Hua, X and Yu, G and Shi, J}, title = {Diversity and composition of the adult fecal microbiome associated with history of cesarean birth or appendectomy: Analysis of the American Gut Project.}, journal = {EBioMedicine}, volume = {1}, number = {2-3}, pages = {167-172}, pmid = {25601913}, issn = {2352-3964}, support = {ZIA CP010214-03//Intramural NIH HHS/United States ; ZIA CP010214-02//Intramural NIH HHS/United States ; ZIA CP010214-01//Intramural NIH HHS/United States ; ZIA CP010214-4//Intramural NIH HHS/United States ; ZIA CP010214-05//Intramural NIH HHS/United States ; }, abstract = {BACKGROUND: Cesarean birth is associated with altered composition of the neonate's microbiota and with increased risk for obesity and other diseases later in life. The mechanisms of these associations, and whether cesarean birth is associated with an altered adult microbiota, are unknown.<br><br>METHODS: In 1097 adult volunteers without diabetes, inflammatory bowel disease, or recent antibiotic use, fecal microbiome metrics were compared by history of cesarean birth (N=92) or appendectomy (N=115). Associations with potential confounders, microbiome alpha diversity, and individual microbial taxa were estimated by logistic regression. Permutation tests assessed differences in microbial composition (beta diversity) based on Jensen-Shannon divergence.<br><br>FINDINGS: Cesarean birth history was associated with younger age; appendectomy with older age and higher body mass index. Neither was associated with fecal microbiome alpha diversity. Microbial composition at all taxonomic levels differed significantly with cesarean birth (P&#x2264;0.008) but not with appendectomy (P&#x2265;0.29). Relative abundance differed nominally for 17 taxa with cesarean birth and for 22 taxa with appendectomy, none of which was significant with adjustment for multiple comparisons.<br><br>INTERPRETATION: Adults born by cesarean section appear to have a distinctly different composition of their fecal microbial population. Whether this distinction was acquired during birth, and whether it affects risk of disease during adulthood, are unknown.}, }
@article {pmid25600098, year = {2015}, author = {Whiteside, SA and Razvi, H and Dave, S and Reid, G and Burton, JP}, title = {The microbiome of the urinary tract--a role beyond infection.}, journal = {Nature reviews. Urology}, volume = {12}, number = {2}, pages = {81-90}, pmid = {25600098}, issn = {1759-4820}, mesh = {Adjuvants, Immunologic/therapeutic use ; BCG Vaccine/therapeutic use ; Carcinoma, Transitional Cell/drug therapy/*microbiology ; Gastrointestinal Microbiome ; Humans ; *Microbiota ; Urinary Bladder Neoplasms/drug therapy/*microbiology ; Urinary Tract/*microbiology ; Urinary Tract Infections/*microbiology ; Urolithiasis/microbiology ; }, abstract = {Urologists rarely need to consider bacteria beyond their role in infectious disease. However, emerging evidence shows that the microorganisms inhabiting many sites of the body, including the urinary tract--which has long been assumed sterile in healthy individuals--might have a role in maintaining urinary health. Studies of the urinary microbiota have identified remarkable differences between healthy populations and those with urologic diseases. Microorganisms at sites distal to the kidney, bladder and urethra are likely to have a profound effect on urologic health, both positive and negative, owing to their metabolic output and other contributions. Connections between the gut microbiota and renal stone formation have already been discovered. In addition, bacteria are also used in the prevention of bladder cancer recurrence. In the future, urologists will need to consider possible influences of the microbiome in diagnosis and treatment of certain urological conditions. New insights might provide an opportunity to predict the risk of developing certain urological diseases and could enable the development of innovative therapeutic strategies.}, }
@article {pmid25595150, year = {2015}, author = {Chuong, KH and O'Doherty, KC and Secko, DM}, title = {Media Discourse on the Social Acceptability of Fecal Transplants.}, journal = {Qualitative health research}, volume = {25}, number = {10}, pages = {1359-1371}, doi = {10.1177/1049732314568199}, pmid = {25595150}, issn = {1049-7323}, support = {//Canadian Institutes of Health Research/Canada ; }, mesh = {Canada ; Fecal Microbiota Transplantation/*psychology ; Gastrointestinal Microbiome ; Humans ; Mass Media/*statistics &amp; numerical data ; }, abstract = {Advances in human microbiome research have generated considerable interest in elucidating the role of bacteria in health and the application of microbial ecosystem therapies and probiotics. Fecal transplants involve the introduction of gut microbes from a healthy donor's stool to the patient and have been documented as effective for treating Clostridium difficile infections (CDIs) and some other gastrointestinal disorders. However, the treatment has encountered regulatory hurdles preventing widespread uptake. We examined dominant representations of fecal transplants in Canadian media and found that fecal transplants are often represented as being inherently disgusting or distasteful (the "ick factor"). This "ick factor" is used to construct different messages about the treatment's social acceptability and legitimacy. We conclude that an over-emphasis on the "ick factor" constrains public discourse from a more nuanced discussion of the social challenges, scientific concerns, and regulatory issues surrounding the treatment.}, }
@article {pmid25594724, year = {2015}, author = {Macomber, L and Minkara, MS and Hausinger, RP and Merz, KM}, title = {Reduction of urease activity by interaction with the flap covering the active site.}, journal = {Journal of chemical information and modeling}, volume = {55}, number = {2}, pages = {354-361}, pmid = {25594724}, issn = {1549-960X}, support = {R01 DK045686/DK/NIDDK NIH HHS/United States ; R01 GM066859/GM/NIGMS NIH HHS/United States ; DK045686/DK/NIDDK NIH HHS/United States ; GM066859/GM/NIGMS NIH HHS/United States ; }, mesh = {Amino Acid Sequence ; Amino Acid Substitution ; Catalytic Domain/drug effects ; Catechin/analogs &amp; derivatives/pharmacology ; Cysteine/chemistry ; Enterobacter aerogenes/enzymology ; Enzyme Inhibitors/*chemistry/*pharmacology ; High-Throughput Screening Assays/methods ; Humans ; Models, Molecular ; Mutagenesis, Site-Directed ; Protein Conformation ; Quercetin/pharmacology ; Small Molecule Libraries ; Structure-Activity Relationship ; Urease/*antagonists &amp; inhibitors/*chemistry/genetics ; }, abstract = {With the increasing appreciation for the human microbiome coupled with the global rise of antibiotic resistant organisms, it is imperative that new methods be developed to specifically target pathogens. To that end, a novel computational approach was devised to identify compounds that reduce the activity of urease, a medically important enzyme of Helicobacter pylori, Proteus mirabilis, and many other microorganisms. Urease contains a flexible loop that covers its active site; Glide was used to identify small molecules predicted to lock this loop in an open conformation. These compounds were screened against the model urease from Klebsiella aerogenes, and the natural products epigallocatechin and quercetin were shown to inhibit at low and high micromolar concentrations, respectively. These molecules exhibit a strong time-dependent inactivation of urease that was not due to their oxygen sensitivity. Rather, these compounds appear to inactivate urease by reacting with a specific Cys residue located on the flexible loop. Substitution of this cysteine by alanine in the C319A variant increased the urease resistance to both epigallocatechin and quercetin, as predicted by the computational studies. Protein dynamics are integral to the function of many enzymes; thus, identification of compounds that lock an enzyme into a single conformation presents a useful approach to define potential inhibitors.}, }
@article {pmid25585878, year = {2015}, author = {Rózsa, L and Apari, P and Müller, V}, title = {The microbiome mutiny hypothesis: can our microbiome turn against us when we are old or seriously ill?.}, journal = {Biology direct}, volume = {10}, number = {}, pages = {3}, pmid = {25585878}, issn = {1745-6150}, mesh = {*Aging ; Humans ; Microbiota/*genetics ; *Phenotype ; Virulence ; }, abstract = {BACKGROUND: The symbiotic organisms of the healthy microbiome tend to be harmless or even beneficial for the host; however, some symbionts are able to adjust their virulence in response to external stimuli. Evolutionary theory suggests that optimal virulence might increase if the mortality of the host (from unrelated causes) increases.<br><br>We hypothesize that microorganisms of the human microbiome may be capable of a coordinated phenotypic switch to higher virulence ("microbiome mutiny") in old or seriously ill people, to optimize their transmission under the conditions of increased background mortality. This proposed virulence shift might contribute to the death of old or seriously ill people even in the absence of apparent disease.<br><br>TESTING THE HYPOTHESIS: Testable predictions of the hypothesis include increased expression of virulence factors in isolates of the same species of the microbiome obtained from ailing/old versus healthy/young individuals, and the existence of microbial mechanisms to assess the general condition (background mortality) of the host. Such tests are going to be important to distinguish the cases of "microbiome mutiny" from the situation where opportunistic infections or increased effective virulence arise from relaxed immune control in ailing or old individuals in the absence of changes in the symbionts/pathogens.<br><br>Elucidating this potential mechanism might open up new possibilities for the clinical management of age related health issues and critical injuries or disease. Targeted prophylaxis against the microbes capable of virulence shifts could break the harmful feedback loop between deteriorating health and the "mutiny" of the microbiome.}, }
@article {pmid25584460, year = {2015}, author = {D'Argenio, V and Salvatore, F}, title = {The role of the gut microbiome in the healthy adult status.}, journal = {Clinica chimica acta; international journal of clinical chemistry}, volume = {451}, number = {Pt A}, pages = {97-102}, doi = {10.1016/j.cca.2015.01.003}, pmid = {25584460}, issn = {1873-3492}, mesh = {Adult ; Bacteria/*metabolism ; Gastrointestinal Microbiome/genetics/*physiology ; *Health ; Health Status ; Humans ; }, abstract = {The gut microbiome, which hosts up to 1000 bacterial species that encode about 5 million genes, perform many of the functions required for host physiology and survival. Consequently, it is also known as "our forgotten organ". The recent development of next-generation sequencing technologies has greatly improved metagenomic research. In particular, it has increased our knowledge about the microbiome and its mutually beneficial relationships with the human host. Microbial colonization begins immediately at birth. Although influenced by a variety of stimuli, namely, diet, physical activity, travel, illness, hormonal cycles and therapies, the microbiome is practically stable in healthy adults. This suggests that the microbiome plays a role in the maintenance of a healthy state in adulthood. Quantitative and qualitative alterations in the composition of the gut microbiome could lead to pathological dysbiosis, and have been related to an increasing number of intestinal and extra-intestinal diseases. With the increase in knowledge about gut microbiome functions, it is becoming increasingly more possible to develop novel diagnostic, prognostic and, most important, therapeutic strategies based on microbiome manipulation.}, }
@article {pmid25583170, year = {2015}, author = {Horton, JM and Gao, Z and Sullivan, DM and Shopsin, B and Perez-Perez, GI and Blaser, MJ}, title = {The cutaneous microbiome in outpatients presenting with acute skin abscesses.}, journal = {The Journal of infectious diseases}, volume = {211}, number = {12}, pages = {1895-1904}, pmid = {25583170}, issn = {1537-6613}, support = {P30 CA016087/CA/NCI NIH HHS/United States ; R01 AI103268/AI/NIAID NIH HHS/United States ; UH2 AR057506/AR/NIAMS NIH HHS/United States ; }, mesh = {Abscess/*diagnosis ; Adolescent ; Adult ; Female ; High-Throughput Nucleotide Sequencing ; Humans ; Male ; *Microbiota ; *Outpatients ; Real-Time Polymerase Chain Reaction ; Skin/*microbiology ; Skin Diseases, Bacterial/*diagnosis ; Surveys and Questionnaires ; Young Adult ; }, abstract = {BACKGROUND: Previous studies have demonstrated an association between antibiotic use and the development of skin abscesses. We tested the hypothesis that alterations in the composition of the cutaneous microbiota may predispose individuals to skin abscesses.<br><br>METHODS: We studied 25 patients with skin abscesses and 25 age-matched controls, who each completed a questionnaire. Skin swab samples were obtained for DNA analysis from 4 sites around the abscess site (hereafter, "peri-abscess specimens") and from similar sites on the patient's contralateral side and on healthy control subjects. DNA was extracted and analyzed by quantitative polymerase chain reaction (qPCR) and high-throughput sequencing. The purulent abscess drainage was sent for culture.<br><br>RESULTS: Fifteen patients with abscess were infected with Staphylococcus aureus. Use of nuc qPCR to quantitate S. aureus revealed a significantly greater frequency of positive results for peri-abscess and contralateral skin samples, compared with control skin specimens. Analysis of community structure showed greater heterogeneity in the control samples than in the peri-abscess and contralateral samples. Metagenomic analysis detected significantly more predicted genes related to metabolic activity in the peri-abscess specimens than in the control samples.<br><br>CONCLUSIONS: The peri-abscess microbiome was similar to the contralateral microbiome, but both microbiomes differed from that for control patients. Host characteristics affecting microbial populations might be important determinants of abscess risk.}, }
@article {pmid25580813, year = {2015}, author = {Chilton, SN and Burton, JP and Reid, G}, title = {Inclusion of fermented foods in food guides around the world.}, journal = {Nutrients}, volume = {7}, number = {1}, pages = {390-404}, pmid = {25580813}, issn = {2072-6643}, mesh = {Diet ; *Fermentation ; *Food Microbiology ; Food, Organic ; Humans ; *Nutrition Policy ; Probiotics/administration &amp; dosage ; Randomized Controlled Trials as Topic ; }, abstract = {Fermented foods have been a well-established part of the human diet for thousands of years, without much of an appreciation for, or an understanding of, their underlying microbial functionality, until recently. The use of many organisms derived from these foods, and their applications in probiotics, have further illustrated their impact on gastrointestinal wellbeing and diseases affecting other sites in the body. However, despite the many benefits of fermented foods, their recommended consumption has not been widely translated to global inclusion in food guides. Here, we present the case for such inclusion, and challenge health authorities around the world to consider advocating for the many benefits of these foods.}, }
@article {pmid25577384, year = {2015}, author = {Bruno, F and Marinella, M and Santamaria, M}, title = {e-DNA meta-barcoding: from NGS raw data to taxonomic profiling.}, journal = {Methods in molecular biology (Clifton, N.J.)}, volume = {1269}, number = {}, pages = {257-278}, doi = {10.1007/978-1-4939-2291-8_16}, pmid = {25577384}, issn = {1940-6029}, mesh = {Animals ; Computational Biology/*methods ; High-Throughput Nucleotide Sequencing/*methods ; Humans ; Metagenomics ; RNA, Ribosomal, 16S/genetics ; }, abstract = {In recent years, thanks to the essential support provided by the Next-Generation Sequencing (NGS) technologies, Metagenomics is enabling the direct access to the taxonomic and functional composition of mixed microbial communities living in any environmental niche, without the prerequisite to isolate or culture the single organisms. This approach has already been successfully applied for the analysis of many habitats, such as water or soil natural environments, also characterized by extreme physical and chemical conditions, food supply chains, and animal organisms, including humans. A shotgun sequencing approach can lead to investigate both organisms and genes diversity. Anyway, if the purpose is limited to explore the taxonomic complexity, an amplicon-based approach, based on PCR-targeted sequencing of selected genetic species markers, commonly named "meta-barcodes", is desirable. Among the genomic regions most widely used for the discrimination of bacterial organisms, in some cases up to the species level, some hypervariable domains of the gene coding for the 16S rRNA occupy a prominent place. The amplification of a certain meta-barcode from a microbial community through the use of PCR primers able to work in the entire considered taxonomic group is the first task after the extraction of the total DNA. Generally, this step is followed by the high-throughput sequencing of the resulting amplicons libraries by means of a selected NGS platform. Finally, the interpretation of the huge amount of produced data requires appropriate bioinformatics tools and know-how in addition to efficient computational resources. Here a computational methodology suitable for the taxonomic characterization of 454 meta-barcode sequences is described in detail. In particular, a dataset covering the V1-V3 region belonging to the bacterial 16S rRNA coding gene and produced in the Human Microbiome Project (HMP) from a palatine tonsils sample is analyzed. The proposed exercise includes the basic steps to manage raw sequencing data, remove amplification and pyrosequencing errors, and finally map sequences on the taxonomy.}, }
@article {pmid25559405, year = {2015}, author = {Wynendaele, E and Verbeke, F and D'Hondt, M and Hendrix, A and Van De Wiele, C and Burvenich, C and Peremans, K and De Wever, O and Bracke, M and De Spiegeleer, B}, title = {Crosstalk between the microbiome and cancer cells by quorum sensing peptides.}, journal = {Peptides}, volume = {64}, number = {}, pages = {40-48}, doi = {10.1016/j.peptides.2014.12.009}, pmid = {25559405}, issn = {1873-5169}, mesh = {Bacillus/physiology ; Enterococcus faecium/physiology ; Escherichia coli/physiology ; Humans ; Microbiota/*physiology ; Neoplasm Invasiveness/*physiopathology ; Neoplasms/microbiology/*physiopathology ; Peptides/*physiology ; Quorum Sensing/*physiology ; }, abstract = {To date, the precise role of the human microbiome in health and disease states remains largely undefined. Complex and selective crosstalk systems between the microbiome and mammalian cells are also not yet reported. Research up till now mainly focused on bacterial synthesis of virulence factors, reactive oxygen/nitrogen species (ROS/RNS) and hydrogen sulphide, as well as on the activation of exogenous mutagen precursors by intestinal bacteria. We discovered that certain quorum sensing peptides, produced by bacteria, interact with mammalian cells, in casu cancer cells: Phr0662 (Bacillus sp.), EntF-metabolite (Enterococcus faecium) and EDF-derived (Escherichia coli) peptides initiate HCT-8/E11 colon cancer cell invasion, with Phr0662 also promoting angiogenesis. Our findings thus indicate that the human microbiome, through their quorum sensing peptides, may be one of the factors responsible for cancer metastasis.}, }
@article {pmid25559298, year = {2015}, author = {Warinner, C and Speller, C and Collins, MJ and Lewis, CM}, title = {Ancient human microbiomes.}, journal = {Journal of human evolution}, volume = {79}, number = {}, pages = {125-136}, pmid = {25559298}, issn = {1095-8606}, support = {/WT_/Wellcome Trust/United Kingdom ; R01 GM089886/GM/NIGMS NIH HHS/United States ; R01 GM089886)/GM/NIGMS NIH HHS/United States ; }, mesh = {Dental Calculus/microbiology ; Diet ; Feces/microbiology ; Health/history ; High-Throughput Nucleotide Sequencing ; History, Ancient ; Humans ; Metagenomics ; *Microbiota ; *Paleontology ; }, abstract = {Very recently, we discovered a vast new microbial self: the human microbiome. Our native microbiota interface with our biology and culture to influence our health, behavior, and quality of life, and yet we know very little about their origin, evolution, or ecology. With the advent of industrialization, globalization, and modern sanitation, it is intuitive that we have changed our relationship with microbes, but we have little information about the ancestral state of our microbiome, and we therefore lack a foundation for characterizing this change. High-throughput sequencing has opened up new opportunities in the field of paleomicrobiology, allowing us to investigate the evolution of the complex microbial ecologies that inhabit our bodies. By focusing on recent coprolite and dental calculus research, we explore how emerging research on ancient human microbiomes is changing the way we think about ancient disease and how archaeological studies can contribute to a medical understanding of health and nutrition today.}, }
@article {pmid25557805, year = {2015}, author = {Starr, M}, title = {Paediatric infectious diseases: the last 50 years.}, journal = {Journal of paediatrics and child health}, volume = {51}, number = {1}, pages = {12-15}, doi = {10.1111/jpc.12795}, pmid = {25557805}, issn = {1440-1754}, mesh = {Anti-Bacterial Agents/therapeutic use ; Australia ; Child ; Communicable Disease Control/*history ; Communicable Diseases/diagnosis/drug therapy/epidemiology/*history ; Drug Resistance, Bacterial ; Global Health ; History, 20th Century ; History, 21st Century ; Humans ; Pediatrics/*history ; }, abstract = {Many advances and challenges have occurred in the field of paediatric infectious diseases during the past 50 years. It is impossible to cover all of these in a short review, but a few highlights and lowlights will be covered. These include virtual disappearance of some infectious diseases, emergence of new ones, infections in the immunocompromised, antimicrobial resistance, development of new and improved antimicrobials, improved diagnostic tests and the Human Microbiome Project.}, }
@article {pmid27057323, year = {2015}, author = {Neu, J}, title = {Developmental aspects of maternal-fetal, and infant gut microbiota and implications for long-term health.}, journal = {Maternal health, neonatology and perinatology}, volume = {1}, number = {}, pages = {6}, pmid = {27057323}, issn = {2054-958X}, abstract = {BACKGROUND: Early life interactions between the human host and microbes set the stage for future health and disease.<br><br>FINDINGS: In this review, some of the relationship of the human microbiome effects will be discussed as they relate to preterm delivery, early life diseases seen in prematurely delivered infants, and other childhood and adult maladies which include autoimmunity, allergic diseases, obesity or a healthy phenotype.<br><br>CONCLUSION: Although the data in these areas is just beginning to emerge, this review will provide a brief summary of some of the key research being done and will also speculate on emerging areas where major questions are being raised.}, }
@article {pmid25544325, year = {2014}, author = {Schneider, GW and Winslow, R}, title = {Parts and wholes: the human microbiome, ecological ontology, and the challenges of community.}, journal = {Perspectives in biology and medicine}, volume = {57}, number = {2}, pages = {208-223}, doi = {10.1353/pbm.2014.0016}, pmid = {25544325}, issn = {1529-8795}, mesh = {Ethics, Research ; Humans ; *Metagenome ; *Microbiota ; National Institutes of Health (U.S.) ; Politics ; United States ; }, abstract = {The early results of the Human Microbiome Project, released in June 2012, add to the overwhelming data that show that there are literally trillions of microbes that live in and on each human individual. This research raises profound questions about what it means to be an individual organism, human or otherwise. In this paper, we ask two broad questions: (1) how might we conceive of an individual organism, given these results? and (2) in light of this emerging conception of the individual organism, what are the implications for how humans conceive of their own self-sufficiency and interact with other members of the living world? We highlight the ontological and political presuppositions animating this research and return to Aristotle for insights into how to conceive of and how to behave towards and within a diverse community of interdependent living parts that function together as one.}, }
@article {pmid25529048, year = {2014}, author = {Ettinger, G and MacDonald, K and Reid, G and Burton, JP}, title = {The influence of the human microbiome and probiotics on cardiovascular health.}, journal = {Gut microbes}, volume = {5}, number = {6}, pages = {719-728}, pmid = {25529048}, issn = {1949-0984}, mesh = {Cardiovascular Diseases/metabolism/microbiology/*prevention &amp; control ; Gastrointestinal Tract/metabolism/microbiology ; Humans ; *Microbiota ; Probiotics/*administration &amp; dosage ; }, abstract = {Cardiovascular disease (CVD) is a major cause of death worldwide. Of the many etiological factors, microorganisms constitute one. From the local impact of the gut microbiota on energy metabolism and obesity, to the distal association of periodontal disease with coronary heart disease, microbes have a significant impact on cardiovascular health. In terms of the ability to modulate or influence the microbes, probiotic applications have been considered. These are live microorganisms which when administered in adequate amounts confer a benefit on the host. While a number of reports have established the beneficial abilities of certain probiotic bacterial strains to reduce cholesterol and hypertension, recent research suggests that their use could be more widely applied. This review presents an up-to-date summary of the known associations of the microbiome with CVD, and potential applications of probiotic therapy.}, }
@article {pmid25521415, year = {2014}, author = {Yang, P and Su, X and Ou-Yang, L and Chua, HN and Li, XL and Ning, K}, title = {Microbial community pattern detection in human body habitats via ensemble clustering framework.}, journal = {BMC systems biology}, volume = {8 Suppl 4}, number = {Suppl 4}, pages = {S7}, pmid = {25521415}, issn = {1752-0509}, mesh = {Adult ; Algorithms ; Cluster Analysis ; Computational Biology/*methods ; *Ecosystem ; Female ; Humans ; Male ; *Metagenomics ; *Microbiology ; Sex Factors ; }, abstract = {BACKGROUND: The human habitat is a host where microbial species evolve, function, and continue to evolve. Elucidating how microbial communities respond to human habitats is a fundamental and critical task, as establishing baselines of human microbiome is essential in understanding its role in human disease and health. Recent studies on healthy human microbiome focus on particular body habitats, assuming that microbiome develop similar structural patterns to perform similar ecosystem function under same environmental conditions. However, current studies usually overlook a complex and interconnected landscape of human microbiome and limit the ability in particular body habitats with learning models of specific criterion. Therefore, these methods could not capture the real-world underlying microbial patterns effectively.<br><br>RESULTS: To obtain a comprehensive view, we propose a novel ensemble clustering framework to mine the structure of microbial community pattern on large-scale metagenomic data. Particularly, we first build a microbial similarity network via integrating 1920 metagenomic samples from three body habitats of healthy adults. Then a novel symmetric Nonnegative Matrix Factorization (NMF) based ensemble model is proposed and applied onto the network to detect clustering pattern. Extensive experiments are conducted to evaluate the effectiveness of our model on deriving microbial community with respect to body habitat and host gender. From clustering results, we observed that body habitat exhibits a strong bound but non-unique microbial structural pattern. Meanwhile, human microbiome reveals different degree of structural variations over body habitat and host gender.<br><br>CONCLUSIONS: In summary, our ensemble clustering framework could efficiently explore integrated clustering results to accurately identify microbial communities, and provide a comprehensive view for a set of microbial communities. The clustering results indicate that structure of human microbiome is varied systematically across body habitats and host genders. Such trends depict an integrated biography of microbial communities, which offer a new insight towards uncovering pathogenic model of human microbiome.}, }
@article {pmid25517225, year = {2014}, author = {Flores, GE and Caporaso, JG and Henley, JB and Rideout, JR and Domogala, D and Chase, J and Leff, JW and Vázquez-Baeza, Y and Gonzalez, A and Knight, R and Dunn, RR and Fierer, N}, title = {Temporal variability is a personalized feature of the human microbiome.}, journal = {Genome biology}, volume = {15}, number = {12}, pages = {531}, pmid = {25517225}, issn = {1474-760X}, support = {//Howard Hughes Medical Institute/United States ; }, mesh = {Adult ; Bacteria/*classification/*isolation &amp; purification ; Feces/*microbiology ; Female ; Forehead/*microbiology ; Genome, Bacterial ; Genomics/methods ; Hand/*microbiology ; Healthy Volunteers ; Humans ; Longitudinal Studies ; Male ; *Microbiota ; Middle Aged ; Phylogeny ; Tongue/*microbiology ; Young Adult ; }, abstract = {BACKGROUND: It is now apparent that the complex microbial communities found on and in the human body vary across individuals. What has largely been missing from previous studies is an understanding of how these communities vary over time within individuals. To the extent to which it has been considered, it is often assumed that temporal variability is negligible for healthy adults. Here we address this gap in understanding by profiling the forehead, gut (fecal), palm, and tongue microbial communities in 85 adults, weekly over 3 months.<br><br>RESULTS: We found that skin (forehead and palm) varied most in the number of taxa present, whereas gut and tongue communities varied more in the relative abundances of taxa. Within each body habitat, there was a wide range of temporal variability across the study population, with some individuals harboring more variable communities than others. The best predictor of these differences in variability across individuals was microbial diversity; individuals with more diverse gut or tongue communities were more stable in composition than individuals with less diverse communities.<br><br>CONCLUSIONS: Longitudinal sampling of a relatively large number of individuals allowed us to observe high levels of temporal variability in both diversity and community structure in all body habitats studied. These findings suggest that temporal dynamics may need to be considered when attempting to link changes in microbiome structure to changes in health status. Furthermore, our findings show that, not only is the composition of an individual's microbiome highly personalized, but their degree of temporal variability is also a personalized feature.}, }
@article {pmid25517115, year = {2014}, author = {Labbé, A and Ganopolsky, JG and Martoni, CJ and Prakash, S and Jones, ML}, title = {Bacterial bile metabolising gene abundance in Crohn's, ulcerative colitis and type 2 diabetes metagenomes.}, journal = {PloS one}, volume = {9}, number = {12}, pages = {e115175}, pmid = {25517115}, issn = {1932-6203}, mesh = {Amidohydrolases/genetics ; Animals ; Bacteria/enzymology ; Bile Acids and Salts/*metabolism ; Colitis, Ulcerative/*enzymology/genetics/microbiology ; Crohn Disease/*enzymology/genetics/microbiology ; Databases, Factual ; Diabetes Mellitus, Type 2/*enzymology/genetics/microbiology ; Feces/enzymology/microbiology ; Gastrointestinal Tract/*enzymology/microbiology ; Genes, Bacterial/*genetics ; Humans ; Hydroxysteroid Dehydrogenases/genetics ; *Metagenome ; Metagenomics ; Mice ; Microbiota ; Phylogeny ; }, abstract = {We performed an analysis to determine the importance of bile acid modification genes in the gut microbiome of inflammatory bowel disease and type 2 diabetic patients. We used publicly available metagenomic datasets from the Human Microbiome Project and the MetaHIT consortium, and determined the abundance of bile salt hydrolase gene (bsh), 7 alpha-dehydroxylase gene (adh) and 7-alpha hydroxysteroid dehydrogenase gene (hsdh) in fecal bacteria in diseased populations of Crohn's disease (CD), Ulcerative Colitis (UC) and Type 2 diabetes mellitus (T2DM). Phylum level abundance analysis showed a significant reduction in Firmicute-derived bsh in UC and T2DM patients but not in CD patients, relative to healthy controls. Reduction of adh and hsdh genes was also seen in UC and T2DM patients, while an increase was observed in the CD population as compared to healthy controls. A further analysis of the bsh genes showed significant differences in the correlations of certain Firmicutes families with disease or healthy populations. From this observation we proceeded to analyse BSH protein sequences and identified BSH proteins clusters representing the most abundant strains in our analysis of Firmicute bsh genes. The abundance of the bsh genes corresponding to one of these protein clusters was significantly reduced in all disease states relative to healthy controls. This cluster includes bsh genes derived from Lachospiraceae, Clostridiaceae, Erysipelotrichaceae and Ruminococcaceae families. This metagenomic analysis provides evidence of the importance of bile acid modifying enzymes in health and disease. It further highlights the importance of identifying gene and protein clusters, as the same gene may be associated with health or disease, depending on the strains expressing the enzyme, and differences in the enzymes themselves.}, }
@article {pmid25516618, year = {2014}, author = {Blaser, MJ and Webb, GF}, title = {Host demise as a beneficial function of indigenous microbiota in human hosts.}, journal = {mBio}, volume = {5}, number = {6}, pages = {}, pmid = {25516618}, issn = {2150-7511}, support = {R01 DK090989/DK/NIDDK NIH HHS/United States ; R01 GM063270/GM/NIGMS NIH HHS/United States ; R01 GM63270/GM/NIGMS NIH HHS/United States ; }, mesh = {*Biological Evolution ; Computer Simulation ; *Death ; Humans ; *Longevity ; *Microbiota ; *Reproduction ; }, abstract = {UNLABELLED: The age structure of human populations is exceptional among animal species. Unlike with most species, human juvenility is extremely extended, and death is not coincident with the end of the reproductive period. We examine the age structure of early humans with models that reveal an extraordinary balance of human fertility and mortality. We hypothesize that the age structure of early humans was maintained by mechanisms incorporating the programmed death of senescent individuals, including by means of interactions with their indigenous microorganisms. First, before and during reproductive life, there was selection for microbes that preserve host function through regulation of energy homeostasis, promotion of fecundity, and defense against competing high-grade pathogens. Second, we hypothesize that after reproductive life, there was selection for organisms that contribute to host demise. While deleterious to the individual, the presence of such interplay may be salutary for the overall host population in terms of resource utilization, resistance to periodic diminutions in the food supply, and epidemics due to high-grade pathogens. We provide deterministic mathematical models based on age-structured populations that illustrate the dynamics of such relationships and explore the relevant parameter values within which population viability is maintained. We argue that the age structure of early humans was robust in its balance of the juvenile, reproductive-age, and senescent classes. These concepts are relevant to issues in modern human longevity, including inflammation-induced neoplasia and degenerative diseases of the elderly, which are a legacy of human evolution.<br><br>IMPORTANCE: The extended longevity of modern humans is a very recent societal artifact, although it is inherent in human evolution. The age structure of early humans was balanced by fertility and mortality, with an exceptionally prolonged juvenility. We examined the role of indigenous microbes in early humans as fundamental contributors to this age structure. We hypothesize that the human microbiome evolved mechanisms specific to the mortality of senescent individuals among early humans because their mortality contributed to the stability of the general population. The hypothesis that we present provides new bases for modern medical problems, such as inflammation-induced neoplasia and degenerative diseases of the elderly. We postulate that these mechanisms evolved because they contributed to the stability of early human populations, but their legacy is now a burden on human longevity in the changed modern world.}, }
@article {pmid25500524, year = {2015}, author = {Estrela, S and Whiteley, M and Brown, SP}, title = {The demographic determinants of human microbiome health.}, journal = {Trends in microbiology}, volume = {23}, number = {3}, pages = {134-141}, pmid = {25500524}, issn = {1878-4380}, support = {095831//Wellcome Trust/United Kingdom ; R01 DE020100/DE/NIDCR NIH HHS/United States ; R01 DE023193/DE/NIDCR NIH HHS/United States ; 1R01DE020100/DE/NIDCR NIH HHS/United States ; }, mesh = {Bacteria/genetics/*metabolism ; Demography ; Health ; Humans ; Metagenome ; Microbial Consortia ; *Microbiota ; Phylogeny ; Symbiosis ; }, abstract = {The human microbiome is a vast reservoir of microbial diversity and increasingly recognized to have a fundamental role in human health. In polymicrobial communities, the presence of one species can modulate the demography (i.e., growth and distribution) of other species. These demographic impacts generate feedbacks in multispecies interactions, which can be magnified in spatially structured populations (e.g., host-associated communities). Here, we argue that demographic feedbacks between species are central to microbiome development, shaping whether and how potential metabolic interactions come to be realized between expanding lineages of bacteria. Understanding how demographic feedbacks tune metabolic interactions and in turn shape microbiome structure and function is now a key challenge to our abilities to better manage microbiome health.}, }
@article {pmid25487328, year = {2015}, author = {Warinner, C and Speller, C and Collins, MJ}, title = {A new era in palaeomicrobiology: prospects for ancient dental calculus as a long-term record of the human oral microbiome.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {370}, number = {1660}, pages = {20130376}, pmid = {25487328}, issn = {1471-2970}, support = {097829/Z/11/A//Wellcome Trust/United Kingdom ; }, mesh = {Archaeology/*methods/trends ; Dental Calculus/*microbiology ; *Fossils ; High-Throughput Nucleotide Sequencing/methods/trends ; Humans ; Microbiological Techniques/*methods/trends ; Microbiota/*genetics ; Paleodontology/*methods/trends ; }, abstract = {The field of palaeomicrobiology is dramatically expanding thanks to recent advances in high-throughput biomolecular sequencing, which allows unprecedented access to the evolutionary history and ecology of human-associated and environmental microbes. Recently, human dental calculus has been shown to be an abundant, nearly ubiquitous, and long-term reservoir of the ancient oral microbiome, preserving not only microbial and host biomolecules but also dietary and environmental debris. Modern investigations of native human microbiota have demonstrated that the human microbiome plays a central role in health and chronic disease, raising questions about changes in microbial ecology, diversity and function through time. This paper explores the current state of ancient oral microbiome research and discusses successful applications, methodological challenges and future possibilities in elucidating the intimate evolutionary relationship between humans and their microbes.}, }
@article {pmid25484919, year = {2014}, author = {Zhou, Y and Holland, MJ and Makalo, P and Joof, H and Roberts, CH and Mabey, DC and Bailey, RL and Burton, MJ and Weinstock, GM and Burr, SE}, title = {The conjunctival microbiome in health and trachomatous disease: a case control study.}, journal = {Genome medicine}, volume = {6}, number = {11}, pages = {99}, pmid = {25484919}, issn = {1756-994X}, support = {/WT_/Wellcome Trust/United Kingdom ; 98481/WT_/Wellcome Trust/United Kingdom ; U54 HG004968/HG/NHGRI NIH HHS/United States ; }, abstract = {BACKGROUND: Trachoma, caused by Chlamydia trachomatis, remains the world's leading infectious cause of blindness. Repeated ocular infection during childhood leads to scarring of the conjunctiva, in-turning of the eyelashes (trichiasis) and corneal opacity in later life. There is a growing body of evidence to suggest non-chlamydial bacteria are associated with clinical signs of trachoma, independent of C. trachomatis infection.<br><br>METHODS: We used deep sequencing of the V1-V3 region of the bacterial 16S rRNA gene to characterize the microbiome of the conjunctiva of 220 residents of The Gambia, 105 with healthy conjunctivae and 115 with clinical signs of trachoma in the absence of detectable C. trachomatis infection. Deep sequencing was carried out using the Roche-454 platform. Sequence data were processed and analyzed through a pipeline developed by the Human Microbiome Project.<br><br>RESULTS: The microbiome of healthy participants was influenced by age and season of sample collection with increased richness and diversity seen in younger participants and in samples collected during the dry season. Decreased diversity and an increased abundance of Corynebacterium and Streptococcus were seen in participants with conjunctival scarring compared to normal controls. Abundance of Corynebacterium was higher still in adults with scarring and trichiasis compared to adults with scarring only.<br><br>CONCLUSIONS: Our results indicate that changes in the conjunctival microbiome occur in trachomatous disease; whether these are a cause or a consequence is yet unknown.}, }
@article {pmid25484632, year = {2014}, author = {Huss, J}, title = {Methodology and Ontology in Microbiome Research.}, journal = {Biological theory}, volume = {9}, number = {4}, pages = {392-400}, pmid = {25484632}, issn = {1555-5542}, support = {P50 HG003390/HG/NHGRI NIH HHS/United States ; R03 HG006029/HG/NHGRI NIH HHS/United States ; }, abstract = {Research on the human microbiome has generated a staggering amount of sequence data, revealing variation in microbial diversity at the community, species (or phylotype), and genomic levels. In order to make this complexity more manageable and easier to interpret, new units-the metagenome, core microbiome, and enterotype-have been introduced in the scientific literature. Here, I argue that analytical tools and exploratory statistical methods, coupled with a translational imperative, are the primary drivers of this new ontology. By reducing the dimensionality of variation in the human microbiome, these new units render it more tractable and easier to interpret, and hence serve an important heuristic role. Nonetheless, there are several reasons to be cautious about these new categories prematurely "hardening" into natural units: a lack of constraints on what can be sequenced metagenomically, freedom of choice in taxonomic level in defining a "core microbiome," typological framing of some of the concepts, and possible reification of statistical constructs. Finally, lessons from the Human Genome Project have led to a translational imperative: a drive to derive results from the exploration of microbiome variation that can help to articulate the emerging paradigm of personalized genomic medicine (PGM). There is a tension between the typologizing inherent in much of this research and the personal in PGM.}, }
@article {pmid25476418, year = {2015}, author = {Tralau, T and Sowada, J and Luch, A}, title = {Insights on the human microbiome and its xenobiotic metabolism: what is known about its effects on human physiology?.}, journal = {Expert opinion on drug metabolism &amp; toxicology}, volume = {11}, number = {3}, pages = {411-425}, doi = {10.1517/17425255.2015.990437}, pmid = {25476418}, issn = {1744-7607}, mesh = {Animals ; Endocrine System/metabolism ; Gastrointestinal Tract/*microbiology ; Humans ; Microbiota/*physiology ; Xenobiotics/adverse effects/*metabolism ; }, abstract = {INTRODUCTION: Our microbiome harbours a metabolic capacity far beyond our own. Moreover, its gene pool is highly adaptable and subject to selective pressure, including host exposure to xenobiotics. Yet, the resulting adaptations do not necessarily follow host well-being and can therefore contribute to disease or unfavourable metabolite production.<br><br>AREAS COVERED: This review provides an overview of our host-microbiome relationship in light of bacterial (xenobiotic) metabolism, community dynamics, entero-endocrine crosstalk, dysbiosis and potential therapeutic targets. In addition, it will highlight the need for a systematic analysis of the microbiome's potential for substance toxification.<br><br>EXPERT OPINION: The influence of our microbiota reaches from primary metabolites to secondary effects such as substrate competition or the activation of eukaryotic Phase I and Phase II enzymes. Further on it plays a hitherto underestimated role in drug metabolism, toxicity and pathogenesis. These effects are partly caused by entero-endocrine crosstalk and interference with eukaryotic regulatory networks. On first sight, the resulting concept of a metabolically competent microbiome adds enormous complexity to human physiology. Yet, the potential specificity of microbial targets harbours therapeutic promise for diseases such as diabetes, cancer and psychiatric disorders. A better physiological and biochemical understanding of the microbiome is thus of high priority for academia and biomedical research.}, }
@article {pmid25452698, year = {2014}, author = {Isokpehi, RD and Udensi, UK and Simmons, SS and Hollman, AL and Cain, AE and Olofinsae, SA and Hassan, OA and Kashim, ZA and Enejoh, OA and Fasesan, DE and Nashiru, O}, title = {Evaluative profiling of arsenic sensing and regulatory systems in the human microbiome project genomes.}, journal = {Microbiology insights}, volume = {7}, number = {}, pages = {25-34}, pmid = {25452698}, issn = {1178-6361}, support = {G12 MD007581/MD/NIMHD NIH HHS/United States ; P20 MD006899/MD/NIMHD NIH HHS/United States ; T36 GM095335/GM/NIGMS NIH HHS/United States ; U41 HG006941/HG/NHGRI NIH HHS/United States ; }, abstract = {The influence of environmental chemicals including arsenic, a type 1 carcinogen, on the composition and function of the human-associated microbiota is of significance in human health and disease. We have developed a suite of bioinformatics and visual analytics methods to evaluate the availability (presence or absence) and abundance of functional annotations in a microbial genome for seven Pfam protein families: As(III)-responsive transcriptional repressor (ArsR), anion-transporting ATPase (ArsA), arsenical pump membrane protein (ArsB), arsenate reductase (ArsC), arsenical resistance operon transacting repressor (ArsD), water/glycerol transport protein (aquaporins), and universal stress protein (USP). These genes encode function for sensing and/or regulating arsenic content in the bacterial cell. The evaluative profiling strategy was applied to 3,274 genomes from which 62 genomes from 18 genera were identified to contain genes for the seven protein families. Our list included 12 genomes in the Human Microbiome Project (HMP) from the following genera: Citrobacter, Escherichia, Lactobacillus, Providencia, Rhodococcus, and Staphylococcus. Gene neighborhood analysis of the arsenic resistance operon in the genome of Bacteroides thetaiotaomicron VPI-5482, a human gut symbiont, revealed the adjacent arrangement of genes for arsenite binding/transfer (ArsD) and cytochrome c biosynthesis (DsbD_2). Visual analytics facilitated evaluation of protein annotations in 367 genomes in the phylum Bacteroidetes identified multiple genomes in which genes for ArsD and DsbD_2 were adjacently arranged. Cytochrome c, produced by a posttranslational process, consists of heme-containing proteins important for cellular energy production and signaling. Further research is desired to elucidate arsenic resistance and arsenic-mediated cellular energy production in the Bacteroidetes.}, }
@article {pmid25448477, year = {2015}, author = {Kim, Y and Koh, I and Rho, M}, title = {Deciphering the human microbiome using next-generation sequencing data and bioinformatics approaches.}, journal = {Methods (San Diego, Calif.)}, volume = {79-80}, number = {}, pages = {52-59}, doi = {10.1016/j.ymeth.2014.10.022}, pmid = {25448477}, issn = {1095-9130}, mesh = {Computational Biology/*methods ; DNA, Bacterial/chemistry ; Humans ; Microbiota/*genetics ; }, abstract = {The human microbiome is one of the key factors affecting the host immune system and metabolic functions that are not encoded in the human genome. Culture-independent analysis of the human microbiome using metagenomics approach allows us to investigate the compositions and functions of the human microbiome. Computational methods analyze the microbial community by using specific marker genes or by using shotgun sequencing of the entire microbial community. Taxonomy profiling is conducted by using the reference sequences or by de novo clustering of the specific region of sequences. Functional profiling, which is mainly based on the sequence similarity, is more challenging since about half of ORFs predicted in the metagenomic data could not find homology with known protein families. This review examines computational methods that are valuable for the analysis of human microbiome, and highlights the results of several large-scale human microbiome studies. It is becoming increasingly evident that dysbiosis of the gut microbiome is strongly associated with the development of immune disorder and metabolic dysfunction.}, }
@article {pmid25443179, year = {2015}, author = {Rogers, GB}, title = {The human microbiome: opportunities and challenges for clinical care.}, journal = {Internal medicine journal}, volume = {45}, number = {9}, pages = {889-898}, doi = {10.1111/imj.12650}, pmid = {25443179}, issn = {1445-5994}, mesh = {Adaptive Immunity ; Anti-Infective Agents/administration &amp; dosage/adverse effects ; Dysbiosis/complications/*immunology ; Host-Pathogen Interactions/*immunology ; Humans ; Immunity, Innate ; Metagenomics/*trends ; *Microbiota/drug effects ; }, abstract = {There is a growing appreciation of the importance of the human microbiome to our normal physiology. This complex microbial ecosystem plays a range of roles, including influencing the development and function of our immune systems, providing essential nutrients, regulating metabolism and protecting us from opportunistic infections. Our increasing understanding of these processes is due, to a large extent, to the development of high-throughput sequencing technologies, providing for the first time a means by which complex microbial dynamics can be detailed. There is also a growing recognition that disruption of commensal microbiota, a phenomenon known as dysbiosis, is associated with several common disorders, including inflammatory bowel disease, type 2 diabetes and oncogenesis. Further, where innate immunity fails to protect us, the microbial communities that colonise the external surfaces of our bodies represent a ready source of infection. This review discusses the mechanisms that govern our interaction with our resident microbiota, both in health and disease, the technological advances that allow us to gain insight into these relationships, and the way in which our growing understanding can inform clinical practice.}, }
@article {pmid25440116, year = {2014}, author = {Defazio, J and Fleming, ID and Shakhsheer, B and Zaborina, O and Alverdy, JC}, title = {The opposing forces of the intestinal microbiome and the emerging pathobiome.}, journal = {The Surgical clinics of North America}, volume = {94}, number = {6}, pages = {1151-1161}, pmid = {25440116}, issn = {1558-3171}, support = {UL1 TR000430/TR/NCATS NIH HHS/United States ; P30 DK042086/DK/NIDDK NIH HHS/United States ; R01 GM062344/GM/NIGMS NIH HHS/United States ; T32 GM099697/GM/NIGMS NIH HHS/United States ; 5R01 GM062344-11/GM/NIGMS NIH HHS/United States ; P30 DK42086/DK/NIDDK NIH HHS/United States ; }, mesh = {Anastomotic Leak/microbiology/prevention &amp; control ; Antibiotic Prophylaxis ; Cathartics/adverse effects ; Drug Resistance, Bacterial ; Humans ; Intestines/*microbiology/surgery ; Metagenomics ; *Microbiota/drug effects/genetics ; Postoperative Complications/microbiology/prevention &amp; control ; Preoperative Care/adverse effects/methods ; Proteomics ; Sepsis/etiology/microbiology/prevention &amp; control ; Surgical Wound Infection/*microbiology/prevention &amp; control ; }, abstract = {This article summarizes emerging concepts on the role of the intestinal microbiome in surgical patients. Revolutionary research over the past decade has shown that human beings live in close and constant contact with boundless communities of microbes. Recent innovations in the study of the human microbiome are reviewed. To demonstrate the applicability of these studies to surgical disease, the authors discuss what is known about the role of microbes in the pathogenesis of perioperative complications. Enhanced awareness of the human microbiome will empower clinicians to adopt novel practices in the prevention and treatment of a variety of surgical conditions.}, }
@article {pmid25440055, year = {2014}, author = {Joice, R and Yasuda, K and Shafquat, A and Morgan, XC and Huttenhower, C}, title = {Determining microbial products and identifying molecular targets in the human microbiome.}, journal = {Cell metabolism}, volume = {20}, number = {5}, pages = {731-741}, pmid = {25440055}, issn = {1932-7420}, support = {R01 HG005969/HG/NHGRI NIH HHS/United States ; U54 DK102557/DK/NIDDK NIH HHS/United States ; R01HG005969/HG/NHGRI NIH HHS/United States ; }, mesh = {Bacteria/genetics/metabolism ; Fungi/genetics/metabolism ; Humans ; Metabolic Networks and Pathways ; Metabolomics/methods ; Metagenome ; Metagenomics/methods ; *Microbiota ; Phylogeny ; }, abstract = {Human-associated microbes are the source of many bioactive microbial products (proteins and metabolites) that play key functions both in human host pathways and in microbe-microbe interactions. Culture-independent studies now provide an accelerated means of exploring novel bioactives in the human microbiome; however, intriguingly, a substantial fraction of the microbial metagenome cannot be mapped to annotated genes or isolate genomes and is thus of unknown function. Meta'omic approaches, including metagenomic sequencing, metatranscriptomics, metabolomics, and integration of multiple assay types, represent an opportunity to efficiently explore this large pool of potential therapeutics. In combination with appropriate follow-up validation, high-throughput culture-independent assays can be combined with computational approaches to identify and characterize novel and biologically interesting microbial products. Here we briefly review the state of microbial product identification and characterization and discuss possible next steps to catalog and leverage the large uncharted fraction of the microbial metagenome.}, }
@article {pmid25440050, year = {2014}, author = {Bokulich, NA and Blaser, MJ}, title = {A bitter aftertaste: unintended effects of artificial sweeteners on the gut microbiome.}, journal = {Cell metabolism}, volume = {20}, number = {5}, pages = {701-703}, pmid = {25440050}, issn = {1932-7420}, support = {R01 DK090989/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Female ; Gastrointestinal Tract/*drug effects/*microbiology ; Glucose Intolerance/*chemically induced/*microbiology ; Humans ; Male ; Microbiota/*drug effects ; Sweetening Agents/*adverse effects ; }, abstract = {Intestinal microbial communities regulate a range of host physiological functions, from energy harvest and glucose homeostasis to immune development and regulation. Suez et al. (2014) recently demonstrated that artificial sweeteners alter gut microbial communities, leading to glucose intolerance in both mice and humans.}, }
@article {pmid25439276, year = {2014}, author = {Freedberg, DE and Lebwohl, B and Abrams, JA}, title = {The impact of proton pump inhibitors on the human gastrointestinal microbiome.}, journal = {Clinics in laboratory medicine}, volume = {34}, number = {4}, pages = {771-785}, pmid = {25439276}, issn = {1557-9832}, support = {T32 DK083256 AND/DK/NIDDK NIH HHS/United States ; U54 CA 163004/CA/NCI NIH HHS/United States ; T32 DK083256/DK/NIDDK NIH HHS/United States ; UL1 RR024156/RR/NCRR NIH HHS/United States ; U54 CA163004/CA/NCI NIH HHS/United States ; }, mesh = {Celiac Disease/*etiology/microbiology ; Gastrointestinal Tract/chemistry/drug effects/*microbiology ; Humans ; Hydrogen-Ion Concentration ; Microbiota/*drug effects ; Proton Pump Inhibitors/*adverse effects/chemistry/therapeutic use ; }, abstract = {Potent gastric acid suppression using proton pump inhibitors (PPIs) is common in clinical practice but may have important effects on human health that are mediated through changes in the gastrointestinal microbiome. In the esophagus, PPIs change the normal bacterial milieu to decrease distal esophageal exposure to inflammatory gram-negative bacteria. In the stomach, PPIs alter the abundance and location of gastric Helicobacter pylori and other bacteria. In the small bowel, PPIs cause polymicrobial small bowel bacterial overgrowth and have been associated with the diagnosis of celiac disease. In the colon, PPIs associate with incident but not recurrent Clostridium difficile infection.}, }
@article {pmid25439275, year = {2014}, author = {Jianzhong, H}, title = {The genetic predisposition and the interplay of host genetics and gut microbiome in Crohn disease.}, journal = {Clinics in laboratory medicine}, volume = {34}, number = {4}, pages = {763-770}, pmid = {25439275}, issn = {1557-9832}, support = {K01 DK094986/DK/NIDDK NIH HHS/United States ; }, mesh = {Autophagy/genetics ; Crohn Disease/*genetics/immunology/microbiology/pathology ; Epithelium/microbiology/pathology ; *Genetic Predisposition to Disease ; Host-Pathogen Interactions/genetics ; Humans ; *Microbiota ; }, abstract = {Extensive genetic studies have identified more than 140 loci predisposing to Crohn disease (CD). Several major CD susceptibility genes have been shown to impair biological function with regard to immune response to recognizing and clearance of bacterial infection. Recent human microbiome studies suggest that the gut microbiome composition is differentiated in carriers of many risk variants of major CD susceptibility genes. This interplay between host genetics and its associated gut microbiome may play an essential role in the pathogenesis of CD. The ongoing microbiome research is aimed to investigate the detailed host genetics-microbiome interacting mechanism.}, }
@article {pmid25439068, year = {2014}, author = {Otero, LL and Ruiz, VE and Perez Perez, GI}, title = {Helicobacter pylori: the balance between a role as colonizer and pathogen.}, journal = {Best practice &amp; research. Clinical gastroenterology}, volume = {28}, number = {6}, pages = {1017-1029}, doi = {10.1016/j.bpg.2014.09.003}, pmid = {25439068}, issn = {1532-1916}, mesh = {Gastrointestinal Tract/*microbiology ; Helicobacter Infections/microbiology ; Helicobacter pylori/*pathogenicity ; Humans ; Microbiota/*physiology ; Stomach Neoplasms/microbiology ; }, abstract = {The isolation of Helicobacter pylori from the human stomach produced significant changes in how gastroenterologists, immunologists, epidemiologists, pathologists and microbiologists have approached gastro-duodenal diseases in the last half of the XX century. However, research of this organism has progressed greatly in the first decade of this century, evidence suggest that H. pylori is associated with disease only in humans older than 40 years, while, the lack of H. pylori colonization is associated with the emergence of new diseases, particularly in younger individuals. These differing effects of H. pylori colonization have created two contrasting concepts: the 'bad' and the 'good' Helicobacter. Following from renewed interest in the normal human microbiome, we need to reconsider our definitions and perhaps recognize that H. pylori might be a normal member of the human gastric microbiome in ancient humans that gradually, as results of the improvement in our environment, is disappearing.}, }
@article {pmid25438024, year = {2014}, author = {Francino, MP}, title = {Early development of the gut microbiota and immune health.}, journal = {Pathogens (Basel, Switzerland)}, volume = {3}, number = {3}, pages = {769-790}, pmid = {25438024}, issn = {2076-0817}, abstract = {In recent years, the increase in human microbiome research brought about by the rapidly evolving "omic" technologies has established that the balance among the microbial groups present in the human gut, and their multipronged interactions with the host, are crucial for health. On the other hand, epidemiological and experimental support has also grown for the 'early programming hypothesis', according to which factors that act in utero and early in life program the risks for adverse health outcomes later on. The microbiota of the gut develops during infancy, in close interaction with immune development, and with extensive variability across individuals. It follows that the specific process of gut colonization and the microbe-host interactions established in an individual during this period have the potential to represent main determinants of life-long propensity to immune disease. Although much remains to be learnt on the progression of events by which the gut microbiota becomes established and initiates its intimate relationships with the host, and on the long-term repercussions of this process, recent works have advanced significatively in this direction.}, }
@article {pmid25438009, year = {2014}, author = {Missaghi, B and Barkema, HW and Madsen, KL and Ghosh, S}, title = {Perturbation of the human microbiome as a contributor to inflammatory bowel disease.}, journal = {Pathogens (Basel, Switzerland)}, volume = {3}, number = {3}, pages = {510-527}, pmid = {25438009}, issn = {2076-0817}, abstract = {The human microbiome consist of the composite genome of native flora that have evolved with humanity over millennia and which contains 150-fold more genes than the human genome. A "healthy" microbiome plays an important role in the maintenance of health and prevention of illness, inclusive of autoimmune disease such as inflammatory bowel disease (IBD). IBD is a prevalent spectrum of disorders, most notably defined by Crohn's disease (CD) and ulcerative colitis (UC), which are associated with considerable suffering, morbidity, and cost. This review presents an outline of the loss of a normal microbiome as an etiology of immune dysregulation and IBD pathogenesis initiation. We, furthermore, summarize the knowledge on the role of a healthy microbiome in terms of its diversity and important functional elements and, lastly, conclude with some of the therapeutic interventions and modalities that are now being explored as potential applications of microbiome-host interactions.}, }
@article {pmid27088046, year = {2014}, author = {Rivera-Amill, V}, title = {The Human Microbiome and the Immune System: An Ever Evolving Understanding.}, journal = {Journal of clinical &amp; cellular immunology}, volume = {5}, number = {6}, pages = {}, pmid = {27088046}, issn = {2155-9899}, support = {G12 MD007579/MD/NIMHD NIH HHS/United States ; }, }
@article {pmid25430522, year = {2016}, author = {Salvucci, E}, title = {Microbiome, holobiont and the net of life.}, journal = {Critical reviews in microbiology}, volume = {42}, number = {3}, pages = {485-494}, doi = {10.3109/1040841X.2014.962478}, pmid = {25430522}, issn = {1549-7828}, mesh = {Animals ; Bacteria/classification/genetics/isolation &amp; purification ; *Bacterial Physiological Phenomena ; Biological Evolution ; Humans ; *Microbiota ; *Symbiosis ; }, abstract = {Holistic emerging approaches allow us to understand that every organism is the result of integration mechanisms observed at every level of nature: integration of DNA from virus and bacteria in metazoans, endosymbiotic relationships and holobionts. Horizontal gene transfer events in Bacteria, Archaea and Eukaryotes have resulted in the chimeric nature of genomes. As a continuity of this genomic landscape, the human body contains more bacterial than human cells. Human microbiome has co-evolved with the human being as a unity called holobiont. The loss of part of our microbiome along evolution can explain the continuous increasing incidence of immune and inflammatory-related diseases. Life is a continuous process in which the organism experiences its environment and this interaction impacts in the epigenetic system and the genomic structure. The emerging perspectives restitute the great importance of Lamarck's theoretical contributions (the milieu) and Darwin's pangenesis theory.}, }
@article {pmid25426106, year = {2014}, author = {Mark Welch, JL and Utter, DR and Rossetti, BJ and Mark Welch, DB and Eren, AM and Borisy, GG}, title = {Dynamics of tongue microbial communities with single-nucleotide resolution using oligotyping.}, journal = {Frontiers in microbiology}, volume = {5}, number = {}, pages = {568}, pmid = {25426106}, issn = {1664-302X}, support = {R01 DE022586/DE/NIDCR NIH HHS/United States ; }, abstract = {The human mouth is an excellent system to study the dynamics of microbial communities and their interactions with their host. We employed oligotyping to analyze, with single-nucleotide resolution, oral microbial 16S ribosomal RNA (rRNA) gene sequence data from a time course sampled from the tongue of two individuals, and we interpret our results in the context of oligotypes that we previously identified in the oral data from the Human Microbiome Project. Our previous work established that many of these oligotypes had dramatically different distributions between individuals and across oral habitats, suggesting that they represented functionally different organisms. Here we demonstrate the presence of a consistent tongue microbiome but with rapidly fluctuating proportions of the characteristic taxa. In some cases closely related oligotypes representing strains or variants within a single species displayed fluctuating relative abundances over time, while in other cases an initially dominant oligotype was replaced by another oligotype of the same species. We use this high temporal and taxonomic level of resolution to detect correlated changes in oligotype abundance that could indicate which taxa likely interact synergistically or occupy similar habitats, and which likely interact antagonistically or prefer distinct habitats. For example, we found a strong correlation in abundance over time between two oligotypes from different families of Gamma Proteobacteria, suggesting a close functional or ecological relationship between them. In summary, the tongue is colonized by a microbial community of moderate complexity whose proportional abundance fluctuates widely on time scales of days. The drivers and functional consequences of these community dynamics are not known, but we expect they will prove tractable to future, targeted studies employing taxonomically resolved analysis of high-throughput sequencing data sampled at appropriate temporal intervals and spatial scales.}, }
@article {pmid25423621, year = {2015}, author = {Guthals, A and Boucher, C and Bandeira, N}, title = {The generating function approach for Peptide identification in spectral networks.}, journal = {Journal of computational biology : a journal of computational molecular cell biology}, volume = {22}, number = {5}, pages = {353-366}, pmid = {25423621}, issn = {1557-8666}, support = {P41 GM103484/GM/NIGMS NIH HHS/United States ; 8 P41 GM103485-05/GM/NIGMS NIH HHS/United States ; }, mesh = {Algorithms ; Computer Simulation ; Databases, Protein ; Humans ; *Models, Statistical ; Peptide Library ; Peptides/*analysis ; Proteomics/methods/*statistics &amp; numerical data ; *Software ; Tandem Mass Spectrometry/*statistics &amp; numerical data ; }, abstract = {Tandem mass (MS/MS) spectrometry has become the method of choice for protein identification and has launched a quest for the identification of every translated protein and peptide. However, computational developments have lagged behind the pace of modern data acquisition protocols and have become a major bottleneck in proteomics analysis of complex samples. As it stands today, attempts to identify MS/MS spectra against large databases (e.g., the human microbiome or 6-frame translation of the human genome) face a search space that is 10-100 times larger than the human proteome, where it becomes increasingly challenging to separate between true and false peptide matches. As a result, the sensitivity of current state-of-the-art database search methods drops by nearly 38% to such low identification rates that almost 90% of all MS/MS spectra are left as unidentified. We address this problem by extending the generating function approach to rigorously compute the joint spectral probability of multiple spectra being matched to peptides with overlapping sequences, thus enabling the confident assignment of higher significance to overlapping peptide-spectrum matches (PSMs). We find that these joint spectral probabilities can be several orders of magnitude more significant than individual PSMs, even in the ideal case when perfect separation between signal and noise peaks could be achieved per individual MS/MS spectrum. After benchmarking this approach on a typical lysate MS/MS dataset, we show that the proposed intersecting spectral probabilities for spectra from overlapping peptides improve peptide identification by 30-62%.}, }
@article {pmid25415497, year = {2015}, author = {Dash, S and Clarke, G and Berk, M and Jacka, FN}, title = {The gut microbiome and diet in psychiatry: focus on depression.}, journal = {Current opinion in psychiatry}, volume = {28}, number = {1}, pages = {1-6}, doi = {10.1097/YCO.0000000000000117}, pmid = {25415497}, issn = {1473-6578}, mesh = {Brain/*physiology ; Depressive Disorder/*physiopathology/prevention &amp; control ; Diet ; Gastrointestinal Tract/*microbiology/physiology ; Humans ; Microbiota/*physiology ; }, abstract = {PURPOSE OF REVIEW: With depressive disorders the leading source of disability globally, the identification of new targets for prevention and management is imperative. A rapidly emerging field of research suggests that the microbiome-gut-brain axis is of substantial relevance to mood and behaviour. Similarly, unhealthy diet has recently emerged as a significant correlate of and risk factor for depression. This review provides evidence for the gut microbiota as a key factor mediating the link between diet and depressive illness.<br><br>RECENT FINDINGS: The development of new technologies is affording a better understanding of how diet influences gut microbiota composition and activity and how this may, in turn, influence depressive illness. New interventions are also suggesting the possible utility of pre and probiotic formulations and fermented food in influencing mental health.<br><br>SUMMARY: Although in its early stages, the emerging field of research focused on the human microbiome suggests an important role for the gut microbiota in influencing brain development, behaviour and mood in humans. The recognition that the gut microbiota interacts bidirectionally with other environmental risk factors, such as diet and stress, suggests promise in the development of interventions targeting the gut microbiota for the prevention and treatment of common mental health disorders.}, }
@article {pmid25394236, year = {2015}, author = {Shreiner, AB and Kao, JY and Young, VB}, title = {The gut microbiome in health and in disease.}, journal = {Current opinion in gastroenterology}, volume = {31}, number = {1}, pages = {69-75}, pmid = {25394236}, issn = {1531-7056}, support = {AI090871/AI/NIAID NIH HHS/United States ; UH2 DK083993/DK/NIDDK NIH HHS/United States ; DK087708/DK/NIDDK NIH HHS/United States ; P30 DK034933/DK/NIDDK NIH HHS/United States ; U19 AI090871/AI/NIAID NIH HHS/United States ; DK094775/DK/NIDDK NIH HHS/United States ; R01 DK087708/DK/NIDDK NIH HHS/United States ; UH3 DK083993/DK/NIDDK NIH HHS/United States ; DK083993/DK/NIDDK NIH HHS/United States ; T32 DK094775/DK/NIDDK NIH HHS/United States ; }, mesh = {Enterocolitis, Pseudomembranous/microbiology ; Gastrointestinal Diseases/*microbiology ; Gastrointestinal Tract/*microbiology ; Host-Pathogen Interactions/physiology ; Humans ; Inflammatory Bowel Diseases/microbiology ; Irritable Bowel Syndrome/microbiology ; Microbiota/*physiology ; }, abstract = {PURPOSE OF REVIEW: Recent technological advancements and expanded efforts have led to a tremendous growth in the collective knowledge of the human microbiome. This review will highlight some of the important recent findings in this area of research.<br><br>RECENT FINDINGS: Studies have described the structure and functional capacity of the bacterial microbiome in the healthy state and in a variety of disease states. Downstream analyses of the functional interactions between the host and its microbiome are starting to provide mechanistic insights into these interactions. These data are anticipated to lead to new opportunities for diagnosis, prognosis, and treatment of a variety of human diseases.<br><br>SUMMARY: There is a fast growing collection of data describing the structure and functional capacity of the microbiome in a variety of conditions available to the research community for consideration and further exploration. Ongoing efforts to further characterize the functions of the microbiome and the mechanisms underlying host-microbe interactions will provide a better understanding of the role of the microbiome in health and disease.}, }
@article {pmid25392516, year = {2014}, author = {Mayer, EA and Knight, R and Mazmanian, SK and Cryan, JF and Tillisch, K}, title = {Gut microbes and the brain: paradigm shift in neuroscience.}, journal = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, volume = {34}, number = {46}, pages = {15490-15496}, pmid = {25392516}, issn = {1529-2401}, support = {P30 DK041301/DK/NIDDK NIH HHS/United States ; R01 DK048351/DK/NIDDK NIH HHS/United States ; R01 MH100556/MH/NIMH NIH HHS/United States ; //Howard Hughes Medical Institute/United States ; }, mesh = {Animals ; Anti-Bacterial Agents/therapeutic use ; Brain/*physiology ; Brain Diseases/drug therapy/physiopathology ; Gastrointestinal Tract/*microbiology ; Humans ; Microbiota/drug effects/*physiology ; Probiotics/therapeutic use ; }, abstract = {The discovery of the size and complexity of the human microbiome has resulted in an ongoing reevaluation of many concepts of health and disease, including diseases affecting the CNS. A growing body of preclinical literature has demonstrated bidirectional signaling between the brain and the gut microbiome, involving multiple neurocrine and endocrine signaling mechanisms. While psychological and physical stressors can affect the composition and metabolic activity of the gut microbiota, experimental changes to the gut microbiome can affect emotional behavior and related brain systems. These findings have resulted in speculation that alterations in the gut microbiome may play a pathophysiological role in human brain diseases, including autism spectrum disorder, anxiety, depression, and chronic pain. Ongoing large-scale population-based studies of the gut microbiome and brain imaging studies looking at the effect of gut microbiome modulation on brain responses to emotion-related stimuli are seeking to validate these speculations. This article is a summary of emerging topics covered in a symposium and is not meant to be a comprehensive review of the subject.}, }
@article {pmid25384764, year = {2014}, author = {Seed, PC}, title = {The human mycobiome.}, journal = {Cold Spring Harbor perspectives in medicine}, volume = {5}, number = {5}, pages = {a019810}, pmid = {25384764}, issn = {2157-1422}, mesh = {Fungi/*genetics ; Humans ; Microbiota/*genetics ; }, abstract = {Fungi are fundamental to the human microbiome, the collection of microbes distributed across and within the body, and the microbiome has been shown, in total, to modify fundamental human physiology, including energy acquisition, vitamin-cofactor availability, xenobiotic metabolism, immune development and function, and even neurological development and behavior. Here, a comprehensive review of current knowledge about the mycobiome, the collective of fungi within the microbiome, highlights methods for its study, diversity between body sites, and dynamics during human development, health, and disease. Early-stage studies show interactions between the mycobiome and other microbes, with host physiology, and in pathogenic and mutualistic phenotypes. Current research portends a vital role for the mycobiome in human health and disease.}, }
@article {pmid25370489, year = {2014}, author = {Burgess, SL and Buonomo, E and Carey, M and Cowardin, C and Naylor, C and Noor, Z and Wills-Karp, M and Petri, WA}, title = {Bone marrow dendritic cells from mice with an altered microbiota provide interleukin 17A-dependent protection against Entamoeba histolytica colitis.}, journal = {mBio}, volume = {5}, number = {6}, pages = {e01817}, pmid = {25370489}, issn = {2150-7511}, support = {T32 AI007496/AI/NIAID NIH HHS/United States ; 5R01 AI026649-25/AI/NIAID NIH HHS/United States ; T32 AI007046/AI/NIAID NIH HHS/United States ; R01 AI026649/AI/NIAID NIH HHS/United States ; R37 AI026649/AI/NIAID NIH HHS/United States ; T32 AI055432/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Clostridium/*growth &amp; development/immunology/physiology ; Dendritic Cells/*immunology ; Disease Models, Animal ; Dysentery, Amebic/*prevention &amp; control ; Entamoeba histolytica/*immunology ; Gastrointestinal Tract/*microbiology ; Interleukin-17/*metabolism ; Mice ; Neutrophils/immunology ; Symbiosis ; }, abstract = {UNLABELLED: There is an emerging paradigm that the human microbiome is central to many aspects of health and may have a role in preventing enteric infection. Entamoeba histolytica is a major cause of amebic diarrhea in developing countries. It colonizes the colon lumen in close proximity to the gut microbiota. Interestingly, not all individuals are equally susceptible to E. histolytica infection. Therefore, as the microbiota is highly variable within individuals, we sought to determine if a component of the microbiota could regulate susceptibility to infection. In studies utilizing a murine model, we demonstrated that colonization of the gut with the commensal Clostridia-related bacteria known as segmented filamentous bacteria (SFB) is protective during E. histolytica infection. SFB colonization in this model was associated with elevated cecal levels of interleukin 17A (IL-17A), dendritic cells, and neutrophils. Bone marrow-derived dendritic cells (BMDCs) from SFB-colonized mice had higher levels of IL-23 production in response to stimulation with trophozoites. Adoptive transfer of BMDCs from an SFB(+) to an SFB(-) mouse was sufficient to provide protection against E. histolytica. IL-17A induction during BMDC transfer was necessary for this protection. This work demonstrates that intestinal colonization with a specific commensal bacterium can provide protection during amebiasis in a murine model. Most importantly, this work demonstrates that the microbiome can mediate protection against an enteric infection via extraintestinal effects on bone marrow-derived dendritic cells.<br><br>IMPORTANCE: Entamoeba histolytica is the causative agent of amebiasis, an infectious disease that contributes significantly to morbidity and mortality due to diarrhea in the developing world. We showed in a murine model that colonization with the commensal members of the Clostridia known as SFB provides protection against E. histolytica and that dendritic cells from SFB-colonized mice alone can recapitulate protection. Understanding interactions between enteropathogens, commensal intestinal bacteria, and the mucosal immune response, including dendritic cells, will help in the development of effective treatments for this disease and other infectious and inflammatory diseases. The demonstration of immune-mediated protection due to communication from the microbiome to the bone marrow represents an emerging field of study that will yield unique approaches to the development of these treatments.}, }
@article {pmid25346017, year = {2015}, author = {Zheng, J and Gänzle, MG and Lin, XB and Ruan, L and Sun, M}, title = {Diversity and dynamics of bacteriocins from human microbiome.}, journal = {Environmental microbiology}, volume = {17}, number = {6}, pages = {2133-2143}, doi = {10.1111/1462-2920.12662}, pmid = {25346017}, issn = {1462-2920}, mesh = {Bacteria/genetics/metabolism ; Bacteriocins/genetics/*metabolism ; Female ; Gastrointestinal Tract/*microbiology ; Humans ; Metagenomics ; *Microbiota ; Mouth/*microbiology ; Respiratory System/*microbiology ; Symbiosis ; Vagina/*microbiology ; }, abstract = {Human commensal microbiota are an important determinant of health and disease of the host. Different human body sites harbour different bacterial microbiota, bacterial communities that maintain a stable balance. However, many of the factors influencing the stabilities of bacterial communities associated with humans remain unknown. In this study, we identified putative bacteriocins produced by human commensal microbiota. Bacteriocins are peptides or proteins with antimicrobial activity that contribute to the stability and dynamics of microbial communities. We employed bioinformatic analyses to identify putative bacteriocin sequences in metagenomic sequences obtained from different human body sites. Prevailing bacterial taxa of the putative bacteriocins producers matched the most abundant organisms in each human body site. Remarkably, we found that samples from different body sites contain different density of putative bacteriocin genes, with the highest in samples from the vagina, the airway, and the oral cavity and the lowest in those from gut. Inherent differences of different body sites thus influence the density and types of bacteriocins produced by commensal bacteria. Our results suggest that bacteriocins play important roles to allow different bacteria to occupy several human body sites, and to establish a long-term commensal relationship with human hosts.}, }
@article {pmid25344977, year = {2014}, author = {Efenberger, M and Wódz, K and Brzezińska-Błaszczyk, E}, title = {[Archaea--the significant inhabitants of human microbiome].}, journal = {Przeglad lekarski}, volume = {71}, number = {6}, pages = {346-351}, pmid = {25344977}, issn = {0033-2240}, mesh = {Archaea/*cytology/drug effects/*physiology ; Drug Resistance, Microbial ; Gastrointestinal Diseases/microbiology ; Humans ; Microbiota/*physiology ; }, abstract = {Archaea, along with bacteria and eucarya are the three domains of life. These microorganisms inhabit variable natural environments but they are also important part of human physiological flora. In this paper we describe archaeal morphology and physiology. We also review the state of knowledge about archaea associated with human microbiome. The potential role of these microorganisms in etiopathogenesis of some human diseases is discussed, as well. Finally, we consider archaeal susceptibility/resistance to antimicrobial agents, including antibiotics.}, }
@article {pmid25344700, year = {2014}, author = {Beatty, M and Guduric-Fuchs, J and Brown, E and Bridgett, S and Chakravarthy, U and Hogg, RE and Simpson, DA}, title = {Small RNAs from plants, bacteria and fungi within the order Hypocreales are ubiquitous in human plasma.}, journal = {BMC genomics}, volume = {15}, number = {1}, pages = {933}, pmid = {25344700}, issn = {1471-2164}, support = {BB/H005498/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Bacteria/*classification/genetics ; Evolution, Molecular ; Humans ; Hypocreales/*classification/genetics ; Metagenome ; Molecular Sequence Data ; Phylogeny ; Plasma/*microbiology ; RNA, Bacterial/genetics ; RNA, Fungal/genetics ; RNA, Plant/genetics ; RNA, Small Untranslated/*blood/*genetics ; Sequence Analysis, RNA ; }, abstract = {BACKGROUND: The human microbiome plays a significant role in maintaining normal physiology. Changes in its composition have been associated with bowel disease, metabolic disorders and atherosclerosis. Sequences of microbial origin have been observed within small RNA sequencing data obtained from blood samples. The aim of this study was to characterise the microbiome from which these sequences are derived.<br><br>RESULTS: Abundant non-human small RNA sequences were identified in plasma and plasma exosomal samples. Assembly of these short sequences into longer contigs was the pivotal novel step in ascertaining their origin by BLAST searches. Most reads mapped to rRNA sequences. The taxonomic profiles of the microbes detected were very consistent between individuals but distinct from microbiomes reported at other sites. The majority of bacterial reads were from the phylum Proteobacteria, whilst for 5 of 6 individuals over 90% of the more abundant fungal reads were from the phylum Ascomycota; of these over 90% were from the order Hypocreales. Many contigs were from plants, presumably of dietary origin. In addition, extremely abundant small RNAs derived from human Y RNAs were detected.<br><br>CONCLUSIONS: A characteristic profile of a subset of the human microbiome can be obtained by sequencing small RNAs present in the blood. The source and functions of these molecules remain to be determined, but the specific profiles are likely to reflect health status. The potential to provide biomarkers of diet and for the diagnosis and prognosis of human disease is immense.}, }
@article {pmid25313086, year = {2014}, author = {Ticak, T and Kountz, DJ and Girosky, KE and Krzycki, JA and Ferguson, DJ}, title = {A nonpyrrolysine member of the widely distributed trimethylamine methyltransferase family is a glycine betaine methyltransferase.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {111}, number = {43}, pages = {E4668-76}, pmid = {25313086}, issn = {1091-6490}, mesh = {Betaine/*metabolism ; Chromatography, Thin Layer ; Desulfitobacterium/genetics/growth &amp; development ; Genes, Bacterial ; Glycine N-Methyltransferase/*metabolism ; Humans ; Lysine/*analogs &amp; derivatives/metabolism ; Methylamines/*metabolism ; Methylation ; Phylogeny ; Real-Time Polymerase Chain Reaction ; }, abstract = {COG5598 comprises a large number of proteins related to MttB, the trimethylamine:corrinoid methyltransferase. MttB has a genetically encoded pyrrolysine residue proposed essential for catalysis. MttB is the only known trimethylamine methyltransferase, yet the great majority of members of COG5598 lack pyrrolysine, leaving the activity of these proteins an open question. Here, we describe the function of one of the nonpyrrolysine members of this large protein family. Three nonpyrrolysine MttB homologs are encoded in Desulfitobacterium hafniense, a Gram-positive strict anaerobe present in both the environment and human intestine. D. hafniense was found capable of growth on glycine betaine with electron acceptors such as nitrate or fumarate, producing dimethylglycine and CO2 as products. Examination of the genome revealed genes for tetrahydrofolate-linked oxidation of a methyl group originating from a methylated corrinoid protein, but no obvious means to carry out corrinoid methylation with glycine betaine. DSY3156, encoding one of the nonpyrrolysine MttB homologs, was up-regulated during growth on glycine betaine. The recombinant DSY3156 protein converts glycine betaine and cob(I)alamin to dimethylglycine and methylcobalamin. To our knowledge, DSY3156 is the first glycine betaine:corrinoid methyltransferase described, and a designation of MtgB is proposed. In addition, DSY3157, an adjacently encoded protein, was shown to be a methylcobalamin:tetrahydrofolate methyltransferase and is designated MtgA. Homologs of MtgB are widely distributed, especially in marine bacterioplankton and nitrogen-fixing plant symbionts. They are also found in multiple members of the human microbiome, and may play a beneficial role in trimethylamine homeostasis, which in recent years has been directly tied to human cardiovascular health.}, }
@article {pmid25311577, year = {2015}, author = {Mao, L and Franke, J}, title = {Symbiosis, dysbiosis, and rebiosis-the value of metaproteomics in human microbiome monitoring.}, journal = {Proteomics}, volume = {15}, number = {5-6}, pages = {1142-1151}, doi = {10.1002/pmic.201400329}, pmid = {25311577}, issn = {1615-9861}, mesh = {Biomarkers/analysis ; *Dysbiosis ; Humans ; Metagenomics/*methods ; *Microbiota ; Proteomics/*methods ; *Symbiosis ; Systems Biology ; }, abstract = {As just one species in the larger ecosystem, the health and disease status of human beings is highly dependent on other biological species in their environment, both inside and outside of the human body. Since proteins are the major functional building blocks of the biological world, most homeostasis regulations are realized at the protein level. Diagnosis-oriented monitoring of cross-species proteostasis will constitute a solid basis for next-generation preventive medicine. After a brief review of the history and state-of-the-art of metaproteomics in the field of environmental health research, focus of this perspective article will be put on the role of cross-species joint efforts in symbiosis, dysbiosis, and rebiosis of the human gut during human development, pathogenesis, and aging. The distinctive merit of metaproteomics on health state monitoring will be given special attention. Questions to be addressed include: How this microbial ecosystems in and around humans beings coevolve and stabilize during human development and aging? How the grade of microbial virulence is controlled at the community level? What happens upon temporary or ultimate homeostasis breakdown? How metaproteomics will affect next-generation diagnostics and preventive medicine? As an increasing amount of data becomes available, researchers need to become ever more hypothesis-oriented, so as not to be lost in sea of data, but instead efficiently extract the insights from "Big data." Future directions of metaproteomic research and its integration with other "omics" will be suggested, including the sophisticated use of systems biological approaches such as predictive modeling and simulations, in order to truly serve next-generation medicine.}, }
@article {pmid25308076, year = {2014}, author = {Fox, EP and Cowley, ES and Nobile, CJ and Hartooni, N and Newman, DK and Johnson, AD}, title = {Anaerobic bacteria grow within Candida albicans biofilms and induce biofilm formation in suspension cultures.}, journal = {Current biology : CB}, volume = {24}, number = {20}, pages = {2411-2416}, pmid = {25308076}, issn = {1879-0445}, support = {T32 AI060537/AI/NIAID NIH HHS/United States ; K99AI100896/AI/NIAID NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; T32AI060537/AI/NIAID NIH HHS/United States ; R01 AI083311/AI/NIAID NIH HHS/United States ; R01AI083311/AI/NIAID NIH HHS/United States ; R01 HL117328/HL/NHLBI NIH HHS/United States ; T32 GM007810/GM/NIGMS NIH HHS/United States ; K99 AI100896/AI/NIAID NIH HHS/United States ; R01HL117328/HL/NHLBI NIH HHS/United States ; }, mesh = {Anaerobiosis ; Bacteria, Anaerobic/classification/*physiology ; Biofilms/*growth &amp; development ; Candida albicans/*physiology ; Coculture Techniques ; Microbiological Techniques ; }, abstract = {The human microbiome contains diverse microorganisms, which share and compete for the same environmental niches. A major microbial growth form in the human body is the biofilm state, where tightly packed bacterial, archaeal, and fungal cells must cooperate and/or compete for resources in order to survive. We examined mixed biofilms composed of the major fungal species of the gut microbiome, Candida albicans, and each of five prevalent bacterial gastrointestinal inhabitants: Bacteroides fragilis, Clostridium perfringens, Escherichia coli, Klebsiella pneumoniae, and Enterococcus faecalis. We observed that biofilms formed by C. albicans provide a hypoxic microenvironment that supports the growth of two anaerobic bacteria, even when cultured in ambient oxic conditions that are normally toxic to the bacteria. We also found that coculture with bacteria in biofilms induces massive gene expression changes in C. albicans, including upregulation of WOR1, which encodes a transcription regulator that controls a phenotypic switch in C. albicans, from the "white" cell type to the "opaque" cell type. Finally, we observed that in suspension cultures, C. perfringens induces aggregation of C. albicans into "mini-biofilms," which allow C. perfringens cells to survive in a normally toxic environment. This work indicates that bacteria and C. albicans interactions modulate the local chemistry of their environment in multiple ways to create niches favorable to their growth and survival.}, }
@article {pmid25303518, year = {2014}, author = {Huttenhower, C and Knight, R and Brown, CT and Caporaso, JG and Clemente, JC and Gevers, D and Franzosa, EA and Kelley, ST and Knights, D and Ley, RE and Mahurkar, A and Ravel, J and ,  and White, O}, title = {Advancing the microbiome research community.}, journal = {Cell}, volume = {159}, number = {2}, pages = {227-230}, pmid = {25303518}, issn = {1097-4172}, support = {UH2 AI083264/AI/NIAID NIH HHS/United States ; U54 DK102557/DK/NIDDK NIH HHS/United States ; U54 HG003067/HG/NHGRI NIH HHS/United States ; P30 DK043351/DK/NIDDK NIH HHS/United States ; R01GM103604/GM/NIGMS NIH HHS/United States ; U54DE023798/DE/NIDCR NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; U54HG003067/HG/NHGRI NIH HHS/United States ; UH2AI083264/AI/NIAID NIH HHS/United States ; R01 GM103604/GM/NIGMS NIH HHS/United States ; R01AI089878/AI/NIAID NIH HHS/United States ; R01 AI089878/AI/NIAID NIH HHS/United States ; R01HG005969/HG/NHGRI NIH HHS/United States ; U19AI08404/AI/NIAID NIH HHS/United States ; R01 NR014826/NR/NINR NIH HHS/United States ; U01 HG004866/HG/NHGRI NIH HHS/United States ; U54 DE023798/DE/NIDCR NIH HHS/United States ; R01NR014826/NR/NINR NIH HHS/United States ; }, mesh = {Animals ; *Biomedical Research/methods/standards ; Guidelines as Topic ; Humans ; Microbiological Techniques ; *Microbiota ; National Institutes of Health (U.S.) ; United States ; }, abstract = {The human microbiome has become a recognized factor in promoting and maintaining health. We outline opportunities in interdisciplinary research, analytical rigor, standardization, and policy development for this relatively new and rapidly developing field. Advances in these aspects of the research community may in turn advance our understanding of human microbiome biology.}, }
@article {pmid25303278, year = {2015}, author = {Sherman, MP and Zaghouani, H and Niklas, V}, title = {Gut microbiota, the immune system, and diet influence the neonatal gut-brain axis.}, journal = {Pediatric research}, volume = {77}, number = {1-2}, pages = {127-135}, doi = {10.1038/pr.2014.161}, pmid = {25303278}, issn = {1530-0447}, mesh = {Brain/*physiology ; Dysbiosis/microbiology ; Enterocolitis, Necrotizing/microbiology ; Gastrointestinal Tract/*microbiology/*physiology ; Humans ; Infant, Newborn ; Infant, Newborn, Diseases/*microbiology ; Infant, Very Low Birth Weight ; Microbiota/*physiology ; *Models, Biological ; Sepsis/microbiology ; Signal Transduction/*physiology ; }, abstract = {The conceptual framework for a gut-brain axis has existed for decades. The Human Microbiome Project is responsible for establishing intestinal dysbiosis as a mediator of inflammatory bowel disease, obesity, and neurodevelopmental disorders in adults. Recent advances in metagenomics implicate gut microbiota and diet as key modulators of the bidirectional signaling pathways between the gut and brain that underlie neurodevelopmental and psychiatric disorders in adults. Evidence linking intestinal dysbiosis to neurodevelopmental disease outcomes in preterm infants is emerging. Recent clinical studies show that intestinal dysbiosis precedes late-onset neonatal sepsis and necrotizing enterocolitis in intensive care nurseries. Moreover, strong epidemiologic evidence links late-onset neonatal sepsis and necrotizing enterocolitis in long-term psychomotor disabilities of very-low-birth-weight infants. The notion of the gut-brain axis thereby supports that intestinal microbiota can indirectly harm the brain of preterm infants. In this review, we highlight the anatomy and physiology of the gut-brain axis and describe transmission of stress signals caused by immune-microbial dysfunction in the gut. These messengers initiate neurologic disease in preterm infants. Understanding neural and humoral signaling through the gut-brain axis will offer insight into therapeutic and dietary approaches that may improve the outcomes of very-low-birth-weight infants.}, }
@article {pmid25298059, year = {2014}, author = {Blaser, MJ and Bello, MG}, title = {Maternal antibiotic use and risk of asthma in offspring.}, journal = {The Lancet. Respiratory medicine}, volume = {2}, number = {10}, pages = {e16}, doi = {10.1016/S2213-2600(14)70219-X}, pmid = {25298059}, issn = {2213-2619}, mesh = {Anti-Bacterial Agents/*therapeutic use ; Asthma/*epidemiology ; Female ; Humans ; Mothers/*statistics &amp; numerical data ; Pregnancy ; Pregnancy Complications, Infectious/*drug therapy ; Prenatal Exposure Delayed Effects/*epidemiology ; }, }
@article {pmid25294925, year = {2014}, author = {O'Doherty, KC and Neufeld, JD and Brinkman, FS and Gardner, H and Guttman, DS and Beiko, RG}, title = {Opinion: Conservation and stewardship of the human microbiome.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {111}, number = {40}, pages = {14312-14313}, pmid = {25294925}, issn = {1091-6490}, mesh = {Digestive System/*microbiology ; *Host-Pathogen Interactions ; Humans ; Microbiota/*physiology ; Models, Biological ; }, }
@article {pmid25291137, year = {2014}, author = {Picardo, M and Ottaviani, M}, title = {Skin microbiome and skin disease: the example of rosacea.}, journal = {Journal of clinical gastroenterology}, volume = {48 Suppl 1}, number = {}, pages = {S85-6}, doi = {10.1097/MCG.0000000000000241}, pmid = {25291137}, issn = {1539-2031}, mesh = {Bacteria/classification/*growth &amp; development/immunology ; Host-Pathogen Interactions ; Humans ; Intestinal Mucosa/metabolism ; Intestines/immunology/*microbiology ; *Microbiota ; Rosacea/diagnosis/immunology/metabolism/*microbiology ; Signal Transduction ; Skin/immunology/metabolism/*microbiology ; Toll-Like Receptor 2/immunology/metabolism ; }, abstract = {The imbalance and/or the perturbation of the microbial populations that colonize the skin and that contribute to its defense may represent one of the causes of the development of noninfectious skin diseases. Atopic dermatitis, psoriasis, acne, and rosacea can be listed among these kinds of pathologies. In particular, considering that microbes have been long addressed as having a role in rosacea, this common dermatosis can be an interesting model to evaluate the correlation between microbiome alterations and the occurrence of clinical manifestations. Different microorganisms have been suggested to have a role in rosacea, but no direct correlation with the incidence of the pathology has been clearly defined. Skin microbiome composition is crucial for the correct skin immune functions and recent findings indicate an abnormal activation of innate immune system associated with the rosacea. The enhanced expression of toll-like receptor 2 in the epidermis of rosacea patients can represent a possible explanation for the amplified inflammatory response to external stimuli observed during the disease. In addition, significantly higher small intestinal bacterial overgrowth prevalence in rosacea subjects has been found and its eradication has been associated with a regression of the skin lesions. In conclusion, both skin and gut microbiome seem to have a role, even if synergistic with other factors, in the pathogenesis of rosacea. A deeper knowledge of human microbiome composition and microbe-host interactions will contribute to clarify the mechanism of development of rosacea and possibly will provide innovative therapeutic approaches.}, }
@article {pmid25291122, year = {2014}, author = {Robles-Alonso, V and Guarner, F}, title = {From basic to applied research: lessons from the human microbiome projects.}, journal = {Journal of clinical gastroenterology}, volume = {48 Suppl 1}, number = {}, pages = {S3-4}, doi = {10.1097/MCG.0000000000000242}, pmid = {25291122}, issn = {1539-2031}, mesh = {Bacteria/*classification/genetics ; DNA, Bacterial/genetics ; Dysbiosis ; Host-Pathogen Interactions ; Humans ; Intestines/*microbiology ; Metagenome ; Metagenomics/methods ; *Microbiota ; Ribotyping ; }, abstract = {Two large-scale initiatives of major funding agencies aimed at deciphering the structure and function of the human gut microbiota, namely the NIH's Human Microbiome project and the European MetaHIT project, finalized their research program in 2012.}, }
@article {pmid25267248, year = {2014}, author = {Clemens, R and van Klinken, BJ}, title = {The future of oats in the food and health continuum.}, journal = {The British journal of nutrition}, volume = {112 Suppl 2}, number = {}, pages = {S75-9}, doi = {10.1017/S0007114514002724}, pmid = {25267248}, issn = {1475-2662}, mesh = {*Agriculture ; *Avena/chemistry ; Cardiovascular Diseases/prevention &amp; control ; *Diet ; *Food Supply ; *Functional Food ; *Health ; Humans ; Hypercholesterolemia/prevention &amp; control ; Research ; beta-Glucans/therapeutic use ; }, abstract = {A large body of clinical evidence suggests that the consumption of 3 g or more per d of β-glucan from oats or barley, as part of a diet low in saturated fat and cholesterol, may reduce the risk of CHD. The unique chemical and physical properties of oats and physiological responses to oat consumption contribute to their demonstrated health benefits; other health attributes are still under evaluation. Many of these benefits, such as those associated with a reduced risk of CVD, are codified in health claims by several regulatory agencies, such as the Food and Drug Administration in the USA and the European Food Safety Authority in Europe. Despite these oat-health relationships, an apparent decline in agricultural production, the presence of an array of plant pathogens, and dynamics of climatic conditions may preclude the availability and subsequent consumption of this commodity worldwide. Therefore, it is incumbent on scientists from multiple disciplines to advance research in a spectrum of arenas, including physico-chemical properties of oats, the impact of oats on an array of non-communicable diseases and human microbiome, agricultural practices and environments, and processing technologies that contribute to global food policies.}, }
@article {pmid25263219, year = {2014}, author = {Williams, BB and Van Benschoten, AH and Cimermancic, P and Donia, MS and Zimmermann, M and Taketani, M and Ishihara, A and Kashyap, PC and Fraser, JS and Fischbach, MA}, title = {Discovery and characterization of gut microbiota decarboxylases that can produce the neurotransmitter tryptamine.}, journal = {Cell host &amp; microbe}, volume = {16}, number = {4}, pages = {495-503}, pmid = {25263219}, issn = {1934-6069}, support = {DP2 OD007290/OD/NIH HHS/United States ; GM081879/GM/NIGMS NIH HHS/United States ; T32 EB009383/EB/NIBIB NIH HHS/United States ; K08 DK100638/DK/NIDDK NIH HHS/United States ; OD009180/OD/NIH HHS/United States ; DP5 OD009180/OD/NIH HHS/United States ; K08DK100638/DK/NIDDK NIH HHS/United States ; T32 GM064337/GM/NIGMS NIH HHS/United States ; P30 DK084567/DK/NIDDK NIH HHS/United States ; T32 GM008284/GM/NIGMS NIH HHS/United States ; T32 GM067547/GM/NIGMS NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; P50 GM081879/GM/NIGMS NIH HHS/United States ; OD007290/OD/NIH HHS/United States ; }, mesh = {Amino Acid Sequence ; Bacteria/enzymology/genetics ; Biotransformation ; Carboxy-Lyases/chemistry/*genetics/metabolism ; Crystallography, X-Ray ; Gastrointestinal Tract/*microbiology ; Humans ; *Metagenome ; *Microbiota ; Models, Molecular ; Molecular Sequence Data ; Neurotransmitter Agents/*metabolism ; Phylogeny ; Protein Conformation ; Sequence Homology ; Tryptamines/*metabolism ; Tryptophan/metabolism ; }, abstract = {Several recent studies describe the influence of the gut microbiota on host brain and behavior. However, the mechanisms responsible for microbiota-nervous system interactions are largely unknown. Using a combination of genetics, biochemistry, and crystallography, we identify and characterize two phylogenetically distinct enzymes found in the human microbiome that decarboxylate tryptophan to form the β-arylamine neurotransmitter tryptamine. Although this enzymatic activity is exceedingly rare among bacteria more broadly, analysis of the Human Microbiome Project data demonstrate that at least 10% of the human population harbors at least one bacterium encoding a tryptophan decarboxylase in their gut community. Our results uncover a previously unrecognized enzymatic activity that can give rise to host-modulatory compounds and suggests a potential direct mechanism by which gut microbiota can influence host physiology, including behavior.}, }
@article {pmid25242582, year = {2015}, author = {Solt, I}, title = {The human microbiome and the great obstetrical syndromes: a new frontier in maternal-fetal medicine.}, journal = {Best practice &amp; research. Clinical obstetrics &amp; gynaecology}, volume = {29}, number = {2}, pages = {165-175}, doi = {10.1016/j.bpobgyn.2014.04.024}, pmid = {25242582}, issn = {1532-1932}, mesh = {Chorioamnionitis/microbiology ; Diabetes, Gestational/microbiology ; Female ; Fetal Growth Retardation/microbiology ; Humans ; Maternal-Fetal Exchange ; *Microbiota ; Placenta/microbiology ; Pre-Eclampsia/microbiology ; Pregnancy ; Pregnancy Complications/*microbiology ; Premature Birth/microbiology ; Syndrome ; Uterus/*microbiology ; Vagina/*microbiology ; }, abstract = {The emergence of the concept of the microbiome, together with the development of molecular-based techniques, particularly polymerase chain reaction (PCR) amplification using the 16S ribosomal RNA (rRNA) gene, has dramatically increased the detection of microorganisms, the number of known species, and the understanding of bacterial communities that are relevant to maternal-fetal medicine in health and disease. Culture-independent methods enable characterization of the microbiomes of the reproductive tract of pregnant and nonpregnant women, and have increased our understanding of the role of the uterine microbiome in adverse obstetric outcomes. While bacterial ascent from the vaginal tract is recognized as the primary cause of intrauterine infection, the microbiomes of the gastrointestinal, oral, and respiratory tracts are shown to be involved by means of hematogenous spread. The transmission of maternal microbiomes to the neonate, by vaginal delivery or cesarean section, is shown to affect health from birth to adulthood.}, }
@article {pmid25228989, year = {2014}, author = {Hang, J and Desai, V and Zavaljevski, N and Yang, Y and Lin, X and Satya, RV and Martinez, LJ and Blaylock, JM and Jarman, RG and Thomas, SJ and Kuschner, RA}, title = {16S rRNA gene pyrosequencing of reference and clinical samples and investigation of the temperature stability of microbiome profiles.}, journal = {Microbiome}, volume = {2}, number = {}, pages = {31}, pmid = {25228989}, issn = {2049-2618}, abstract = {BACKGROUND: Sample storage conditions, extraction methods, PCR primers, and parameters are major factors that affect metagenomics analysis based on microbial 16S rRNA gene sequencing. Most published studies were limited to the comparison of only one or two types of these factors. Systematic multi-factor explorations are needed to evaluate the conditions that may impact validity of a microbiome analysis. This study was aimed to improve methodological options to facilitate the best technical approaches in the design of a microbiome study. Three readily available mock bacterial community materials and two commercial extraction techniques, Qiagen DNeasy and MO BIO PowerSoil DNA purification methods, were used to assess procedures for 16S ribosomal DNA amplification and pyrosequencing-based analysis. Primers were chosen for 16S rDNA quantitative PCR and amplification of region V3 to V1. Swabs spiked with mock bacterial community cells and clinical oropharyngeal swabs were incubated at respective temperatures of -80°C, -20°C, 4°C, and 37°C for 4 weeks, then extracted with the two methods, and subjected to pyrosequencing and taxonomic and statistical analyses to investigate microbiome profile stability.<br><br>RESULTS: The bacterial compositions for the mock community DNA samples determined in this study were consistent with the projected levels and agreed with the literature. The quantitation accuracy of abundances for several genera was improved with changes made to the standard Human Microbiome Project (HMP) procedure. The data for the samples purified with DNeasy and PowerSoil methods were statistically distinct; however, both results were reproducible and in good agreement with each other. The temperature effect on storage stability was investigated by using mock community cells and showed that the microbial community profiles were altered with the increase in incubation temperature. However, this phenomenon was not detected when clinical oropharyngeal swabs were used in the experiment.<br><br>CONCLUSIONS: Mock community materials originated from the HMP study are valuable controls in developing 16S metagenomics analysis procedures. Long-term exposure to a high temperature may introduce variation into analysis for oropharyngeal swabs, suggestive of storage at 4&#xb0;C or lower. The observed variations due to sample storage temperature are in a similar range as the intrapersonal variability among different clinical oropharyngeal swab samples.}, }
@article {pmid25220232, year = {2014}, author = {Megerlin, F and Fouassier, E}, title = {[Faecal microbiota transplantation in France: what applicable law?].}, journal = {Annales pharmaceutiques francaises}, volume = {72}, number = {5}, pages = {363-374}, doi = {10.1016/j.pharma.2014.04.003}, pmid = {25220232}, issn = {0003-4509}, mesh = {Clostridioides difficile ; Enterocolitis, Pseudomembranous/microbiology/therapy ; *Fecal Microbiota Transplantation ; Feces/*microbiology ; France ; Gastrointestinal Microbiome ; Humans ; *Legislation, Medical ; }, abstract = {The transplantation of gut microbiota addresses a critical gap in the treatment of recurrent severe Clostridium difficile infection, and clinical trials are ongoing throughout the world for other potential broader clinical indications. As the fecal flora inoculum has currently no legal status under European law, we consider it provisionally a sui generis biological drug rather than a human tissue transplantation, with major implications in terms of legal liability in France. The inoculum obeys a derogation to the pharmaceutical preparation rules, is processed under microbiological control, and therefore should carry a special obligation for informed consent from recipients. Failing industrializable solutions to date, this practice for the modulation of human microbiome suggests that the current legal definition of the biologic drug as well as the rules for donation and use of human-originated substances should be complemented. A new category of therapeutic products could be considered in European law, unless a rapid technological progress (the French Agency ASNM classified FMT as a drug in March 2014).}, }
@article {pmid25215495, year = {2014}, author = {Donia, MS and Cimermancic, P and Schulze, CJ and Wieland Brown, LC and Martin, J and Mitreva, M and Clardy, J and Linington, RG and Fischbach, MA}, title = {A systematic analysis of biosynthetic gene clusters in the human microbiome reveals a common family of antibiotics.}, journal = {Cell}, volume = {158}, number = {6}, pages = {1402-1414}, pmid = {25215495}, issn = {1097-4172}, support = {R01 AI101018/AI/NIAID NIH HHS/United States ; DP2 OD007290/OD/NIH HHS/United States ; R01 DK101674/DK/NIDDK NIH HHS/United States ; T32 GM067547/GM/NIGMS NIH HHS/United States ; R21 AI101722/AI/NIAID NIH HHS/United States ; P50 GM081879/GM/NIGMS NIH HHS/United States ; }, mesh = {Amino Acid Sequence ; Bacteria/*chemistry/classification/*genetics/metabolism ; Biosynthetic Pathways ; Gastrointestinal Tract/microbiology ; Humans ; Metagenomics/*methods ; *Microbiota ; Molecular Sequence Data ; Mouth/microbiology ; Multigene Family ; Peptide Biosynthesis, Nucleic Acid-Independent ; Polyketides/analysis ; }, abstract = {In complex biological systems, small molecules often mediate microbe-microbe and microbe-host interactions. Using a systematic approach, we identified 3,118 small-molecule biosynthetic gene clusters (BGCs) in genomes of human-associated bacteria and studied their representation in 752 metagenomic samples from the NIH Human Microbiome Project. Remarkably, we discovered that BGCs for a class of antibiotics in clinical trials, thiopeptides, are widely distributed in genomes and metagenomes of the human microbiota. We purified and solved the structure of a thiopeptide antibiotic, lactocillin, from a prominent member of the vaginal microbiota. We demonstrate that lactocillin has potent antibacterial activity against a range of Gram-positive vaginal pathogens, and we show that lactocillin and other thiopeptide BGCs are expressed in vivo by analyzing human metatranscriptomic sequencing data. Our findings illustrate the widespread distribution of small-molecule-encoding BGCs in the human microbiome, and they demonstrate the bacterial production of drug-like molecules in humans. PAPERCLIP:}, }
@article {pmid25213620, year = {2014}, author = {Perry, JA and Wright, GD}, title = {Forces shaping the antibiotic resistome.}, journal = {BioEssays : news and reviews in molecular, cellular and developmental biology}, volume = {36}, number = {12}, pages = {1179-1184}, doi = {10.1002/bies.201400128}, pmid = {25213620}, issn = {1521-1878}, mesh = {Anti-Bacterial Agents/pharmacology ; Bacteria/drug effects/*genetics ; Drug Resistance, Bacterial/drug effects/*genetics ; Environmental Monitoring ; Environmental Pollution/prevention &amp; control ; *Gene Transfer, Horizontal ; *Genes, Bacterial ; Humans ; Metagenomics ; Microbiota/genetics ; Mutation ; Selection, Genetic ; *Soil Microbiology ; }, abstract = {Antibiotic resistance has become a problem of global scale. Resistance arises through mutation or through the acquisition of resistance gene(s) from other bacteria in a process called horizontal gene transfer (HGT). While HGT is recognized as an important factor in the dissemination of resistance genes in clinical pathogens, its role in the environment has been called into question by a recent study published in Nature. The authors found little evidence of HGT in soil using a culture-independent functional metagenomics approach, which is in contrast to previous work from the same lab showing HGT between the environment and human microbiome. While surprising at face value, these results may be explained by the lack of selective pressure in the environment studied. Importantly, this work suggests the need for careful monitoring of environmental antibiotic pollution and stringent antibiotic stewardship in the fight against resistance.}, }
@article {pmid25212266, year = {2014}, author = {Wylie, KM and Mihindukulasuriya, KA and Zhou, Y and Sodergren, E and Storch, GA and Weinstock, GM}, title = {Metagenomic analysis of double-stranded DNA viruses in healthy adults.}, journal = {BMC biology}, volume = {12}, number = {}, pages = {71}, pmid = {25212266}, issn = {1741-7007}, support = {U54 HG004968/HG/NHGRI NIH HHS/United States ; U54HG004968/HG/NHGRI NIH HHS/United States ; }, mesh = {Adolescent ; Adult ; DNA Viruses/classification/*genetics/isolation &amp; purification ; DNA, Viral/*analysis ; Female ; High-Throughput Nucleotide Sequencing ; Humans ; Male ; *Metagenome ; Missouri ; Sequence Analysis, DNA ; Texas ; Young Adult ; }, abstract = {BACKGROUND: The Human Microbiome Project (HMP) was undertaken with the goal of defining microbial communities in and on the bodies of healthy individuals using high-throughput, metagenomic sequencing analysis. The viruses present in these microbial communities, the 'human virome', are an important aspect of the human microbiome that is particularly understudied in the absence of overt disease. We analyzed eukaryotic double-stranded DNA (dsDNA) viruses, together with dsDNA replicative intermediates of single-stranded DNA viruses, in metagenomic sequence data generated by the HMP. 706 samples from 102 subjects were studied, with each subject sampled at up to five major body habitats: nose, skin, mouth, vagina, and stool. Fifty-one individuals had samples taken at two or three time points 30 to 359 days apart from at least one of the body habitats.<br><br>RESULTS: We detected an average of 5.5 viral genera in each individual. At least 1 virus was detected in 92% of the individuals sampled. These viruses included herpesviruses, papillomaviruses, polyomaviruses, adenoviruses, anelloviruses, parvoviruses, and circoviruses. Each individual had a distinct viral profile, demonstrating the high interpersonal diversity of the virome. Some components of the virome were stable over time.<br><br>CONCLUSIONS: This study is the first to use high-throughput DNA sequencing to describe the diversity of eukaryotic dsDNA viruses in a large cohort of normal individuals who were sampled at multiple body sites. Our results show that the human virome is a complex component of the microbial flora. Some viruses establish long-term infections that may be associated with increased risk or possibly with protection from disease. A better understanding of the composition and dynamics of the virome may hold important keys to human health.}, }
@article {pmid25211071, year = {2014}, author = {, }, title = {The Integrative Human Microbiome Project: dynamic analysis of microbiome-host omics profiles during periods of human health and disease.}, journal = {Cell host &amp; microbe}, volume = {16}, number = {3}, pages = {276-289}, pmid = {25211071}, issn = {1934-6069}, support = {U54 DK102557/DK/NIDDK NIH HHS/United States ; 8U54DK102557/DK/NIDDK NIH HHS/United States ; U19 AG063744/AG/NIA NIH HHS/United States ; UH3 AI083263/AI/NIAID NIH HHS/United States ; U54 HD080784/HD/NICHD NIH HHS/United States ; U54 DK102556/DK/NIDDK NIH HHS/United States ; 8U54HD080784/HD/NICHD NIH HHS/United States ; U01 HG004866/HG/NHGRI NIH HHS/United States ; 8U54DK102556/DK/NIDDK NIH HHS/United States ; }, mesh = {Bacteria/genetics/isolation &amp; purification ; *Bacterial Physiological Phenomena ; Diabetes Mellitus, Type 2/*microbiology ; Health ; Humans ; Inflammatory Bowel Diseases/*microbiology ; *Microbiota ; Premature Birth/*microbiology ; }, abstract = {Much has been learned about the diversity and distribution of human-associated microbial communities, but we still know little about the biology of the microbiome, how it interacts with the host, and how the host responds to its resident microbiota. The Integrative Human Microbiome Project (iHMP, http://hmp2.org), the second phase of the NIH Human Microbiome Project, will study these interactions by analyzing microbiome and host activities in longitudinal studies of disease-specific cohorts and by creating integrated data sets of microbiome and host functional properties. These data sets will serve as experimental test beds to evaluate new models, methods, and analyses on the interactions of host and microbiome. Here we describe the three models of microbiome-associated human conditions, on the dynamics of preterm birth, inflammatory bowel disease, and type 2 diabetes, and their underlying hypotheses, as well as the multi-omic data types to be collected, integrated, and distributed through public repositories as a community resource.}, }
@article {pmid25209713, year = {2014}, author = {Veiga, P and Pons, N and Agrawal, A and Oozeer, R and Guyonnet, D and Brazeilles, R and Faurie, JM and van Hylckama Vlieg, JE and Houghton, LA and Whorwell, PJ and Ehrlich, SD and Kennedy, SP}, title = {Changes of the human gut microbiome induced by a fermented milk product.}, journal = {Scientific reports}, volume = {4}, number = {}, pages = {6328}, pmid = {25209713}, issn = {2045-2322}, mesh = {Bifidobacterium/growth &amp; development ; Bilophila/growth &amp; development ; Butyrates/metabolism ; *Cultured Milk Products ; Diet ; Feces/microbiology ; Food Microbiology ; Humans ; Irritable Bowel Syndrome/*microbiology ; Lactobacillus delbrueckii/growth &amp; development ; Lactococcus lactis/growth &amp; development ; Microbiota/*genetics ; *Probiotics ; RNA, Ribosomal, 16S/genetics ; Stomach/*microbiology ; Streptococcus thermophilus/growth &amp; development ; }, abstract = {The gut microbiota (GM) consists of resident commensals and transient microbes conveyed by the diet but little is known about the role of the latter on GM homeostasis. Here we show, by a conjunction of quantitative metagenomics, in silico genome reconstruction and metabolic modeling, that consumption of a fermented milk product containing dairy starters and Bifidobacterium animalis potentiates colonic short chain fatty acids production and decreases abundance of a pathobiont Bilophila wadsworthia compared to a milk product in subjects with irritable bowel syndrome (IBS, n = 28). The GM changes parallel improvement of IBS state, suggesting a role of the fermented milk bacteria in gut homeostasis. Our data challenge the view that microbes ingested with food have little impact on the human GM functioning and rather provide support for beneficial health effects.}, }
@article {pmid25209237, year = {2015}, author = {Zvanych, R and Lukenda, N and Li, X and Kim, JJ and Tharmarajah, S and Magarvey, NA}, title = {Systems biosynthesis of secondary metabolic pathways within the oral human microbiome member Streptococcus mutans.}, journal = {Molecular bioSystems}, volume = {11}, number = {1}, pages = {97-104}, doi = {10.1039/c4mb00406j}, pmid = {25209237}, issn = {1742-2051}, support = {10832//Canadian Institutes of Health Research/Canada ; }, mesh = {Antibiosis ; Candida albicans ; Humans ; Immunologic Factors/biosynthesis ; *Metabolic Networks and Pathways ; Metabolome ; Metabolomics/methods ; *Microbiota ; Mouth/*microbiology ; *Secondary Metabolism ; Streptococcus mutans/*metabolism ; }, abstract = {Streptococcus mutans, a Gram-positive human commensal and pathogen, is commonly recognized as a primary causative agent in dental caries. Metabolic activity of this strain results in the creation of acids and secreted products are recognized as pathogenic factors and agents that promote immunomodulation by stimulating the release of pro-inflammatory cytokines. Products of secondary metabolic pathways of microorganisms from the human microbiome are increasingly investigated for their immunomodulatory functions. In this study, we sought to explore the metabolomic output of nonribosomal peptide pathways within the model S. mutans strain, S. mutans UA159, using a systems metabolomic approach to gain in-depth analysis on products created by this organism and probe these molecules for their immunomodulatory function. Comparative metabolomics and biosynthetic studies using wild-type and nonribosomal peptide deletion strains (within the mutanobactin biosynthetic locus), precursor feedings (fatty acid derivatives) led to the identification of 58 metabolites, 13 of which were structurally elucidated. In addition to these, an assembly line derailment product, mutanamide, was also identified and used to assess immunomodulatory properties of mutanobactins and actions relating to their previously reported functions describing hyphal inhibitory profiles in Candida albicans. The results of this study demonstrate both the complexity and the divergent roles of products stemming from this unique biosynthetic assembly line.}, }
@article {pmid25208106, year = {2014}, author = {Landsman, MJ and Sultan, M and Stevens, M and Charabaty, A and Mattar, MC}, title = {Diagnosis and management of common gastrointestinal tract infectious diseases in ulcerative colitis and Crohn's disease patients.}, journal = {Inflammatory bowel diseases}, volume = {20}, number = {12}, pages = {2503-2510}, doi = {10.1097/MIB.0000000000000140}, pmid = {25208106}, issn = {1536-4844}, mesh = {Anti-Infective Agents/*therapeutic use ; Colitis, Ulcerative/*complications ; Crohn Disease/*complications ; Disease Management ; Gastrointestinal Diseases/*diagnosis/*drug therapy/etiology ; Humans ; Prognosis ; }, abstract = {Management of inflammatory bowel disease (IBD), including ulcerative colitis and Crohn's disease, stretches beyond control of flares. Some infections of the gastrointestinal tract are more commonly seen in patients with IBD. Work from the Human Microbiome Project has been instrumental in our understanding of the interplay between the vast gut microbiota and host immune responses. Patients with IBD may be more prone to infectious complications based on their underlying inflammatory disease and variations in their microbiome. Immunosuppressant medications commonly used to treat patients with Crohn's and colitis also play a role in predisposing these patients to acquire these infections. Here, we present a detailed review of the data focusing on the most common infections of the gastrointestinal tract in patients with IBD: Clostridium difficile infections (CDI) and cytomegalovirus (CMV). We will discuss appropriate diagnostic tools and treatment options for these infections. Other less common infections will also be reviewed briefly. Studying the various infections of the gastrointestinal tract in these patients could enhance our understanding of the pathophysiology of IBD.}, }
@article {pmid25205092, year = {2014}, author = {Cameron, EA and Kwiatkowski, KJ and Lee, BH and Hamaker, BR and Koropatkin, NM and Martens, EC}, title = {Multifunctional nutrient-binding proteins adapt human symbiotic bacteria for glycan competition in the gut by separately promoting enhanced sensing and catalysis.}, journal = {mBio}, volume = {5}, number = {5}, pages = {e01441-14}, pmid = {25205092}, issn = {2150-7511}, support = {DK084214/DK/NIDDK NIH HHS/United States ; GM07544/GM/NIGMS NIH HHS/United States ; R01 GM099513/GM/NIGMS NIH HHS/United States ; K01 DK084214/DK/NIDDK NIH HHS/United States ; T32 GM007544/GM/NIGMS NIH HHS/United States ; GM099513/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Bacterial Proteins/genetics/*metabolism ; Bacteroides/genetics/*metabolism ; Carbohydrate Metabolism ; Catalysis ; Gastrointestinal Tract/*microbiology ; *Gene Expression Regulation, Bacterial ; Germ-Free Life ; Humans ; Mice ; Molecular Weight ; Polysaccharides, Bacterial/metabolism ; Starch/*metabolism ; Symbiosis ; }, abstract = {UNLABELLED: To compete for the dynamic stream of nutrients flowing into their ecosystem, colonic bacteria must respond rapidly to new resources and then catabolize them efficiently once they are detected. The Bacteroides thetaiotaomicron starch utilization system (Sus) is a model for nutrient acquisition by symbiotic gut bacteria, which harbor thousands of related Sus-like systems. Structural investigation of the four Sus outer membrane proteins (SusD, -E, -F, and -G) revealed that they contain a total of eight starch-binding sites that we demonstrated, using genetic and biochemical approaches, to play distinct roles in starch metabolism in vitro and in vivo in gnotobiotic mice. SusD, whose homologs are abundant in the human microbiome, is critical for the initial sensing of available starch, allowing sus transcriptional activation at much lower concentrations than without this function. In contrast, seven additional binding sites across SusE, -F, and -G are dispensable for sus activation. However, they optimize the rate of growth on starch in a manner dependent on the expression of the bacterial polysaccharide capsule, suggesting that they have evolved to offset the diffusion barrier created by this structure. These findings demonstrate how proteins with similar biochemical behavior can serve orthogonal functions during different stages of cellular adaptation to nutrients. Finally, we demonstrated in gnotobiotic mice fed a starch-rich diet that the Sus binding sites confer a competitive advantage to B. thetaiotaomicron in vivo in a manner that is dependent on other colonizing microbes. This study reveals how numerically dominant families of carbohydrate-binding proteins in the human microbiome fulfill separate and sometimes cooperative roles to optimize gut commensal bacteria for nutrient acquisition.<br><br>IMPORTANCE: Our intestinal tract harbors trillions of symbiotic microbes. A critical function contributed by this microbial community is the ability to degrade most of the complex carbohydrates in our diet, which not only change from meal to meal but also cannot be digested by our own bodies. A numerically abundant group of gut bacteria called the Bacteroidetes plays a prominent role in carbohydrate digestion in humans and other animals. Currently, the mechanisms that allow this bacterial group to rapidly respond to available carbohydrates and then digest them efficiently are unclear. Here, we present novel functions for four carbohydrate-binding proteins present in one member of the Bacteroidetes, revealing that these proteins serve unique and separable roles in either initial nutrient sensing or subsequent digestion. Because the protein families investigated are numerous in other gut bacteria colonizing nearly all humans and animals, our findings are fundamentally important to understanding how symbiotic microbes assist human digestion.}, }
@article {pmid25196521, year = {2014}, author = {Ye, Y}, title = {Identification of diversity-generating retroelements in human microbiomes.}, journal = {International journal of molecular sciences}, volume = {15}, number = {8}, pages = {14234-14246}, pmid = {25196521}, issn = {1422-0067}, mesh = {Humans ; Microbiota/*genetics ; RNA-Directed DNA Polymerase/genetics ; Retroelements/*genetics ; }, abstract = {Diversity-generating retroelements (DGRs) are a unique family of retroelements that confer selective advantages to their hosts by accelerating the evolution of target genes through a specialized, error-prone, reverse transcription process. First identified in a Bordetella phage (BPP-1), which mediates the phage tropism specificity by generating variability in an involved gene, DGRs were predicted to be present in a larger collection of viral and bacterial species. A minimal DGR system is comprised of a reverse transcriptase (RTase) gene, a template sequence (TR) and a variable region (VR) within a target gene. We developed a computational tool, DGRscan, to allow either de novo identification (based on the prediction of potential template-variable region pairs) or similarity-based searches of DGR systems using known template sequences as the reference. The application of DGRscan to the human microbiome project (HMP) datasets resulted in the identification of 271 non-redundant DGR systems, doubling the size of the collection of known DGR systems. We further identified a large number of putative target genes (651, which share no more than 90% sequence identity at the amino acid level) that are potentially under diversification by the DGR systems. Our study provides the first survey of the DGR systems in the human microbiome, showing that the DGR systems are frequently found in human-associated bacterial communities, although they are of low incidence in individual genomes. Our study also provides functional clues for a large number of genes (reverse transcriptases and target genes) that were previously annotated as proteins of unknown functions or nonspecific functions.}, }
@article {pmid25191338, year = {2014}, author = {Gilbert, SF}, title = {A holobiont birth narrative: the epigenetic transmission of the human microbiome.}, journal = {Frontiers in genetics}, volume = {5}, number = {}, pages = {282}, pmid = {25191338}, issn = {1664-8021}, abstract = {This essay plans to explore, expand, and re-tell the human birth narrative. Usually, human birth narratives focus on the origins of a new individual, focusing on the mother and fetus. This essay discusses birth as the origin of a new community. For not only is the eukaryotic body being reproduced, but so also are the bodies of its symbiotic microbes and so is the set of relationships between these organic components. Several parts of the new narrative are surprising: (1) bacterial symbionts might cause some of the characteristics of pregnancy and prepare a symbiotic community for transfer; (2) the first bacterial colonizers of the mammalian organism my enter the fetus prior to the lysing of the amniotic membrane and birth; (3) the same signals that often cause immunological attack against a microbe may serve under these conditions to signal homeostatic stability between symbiont and host; and (4) the mother may actively provide substances that promote the growth and settlement of helpful bacteria. The birth of the holobiont exemplifies principles of co-evolution, co-development, niche construction, and scaffolding. Birth is nothing less than the passage from one set of symbiotic relationships to another.}, }
@article {pmid25183372, year = {2014}, author = {Henne, K and Li, J and Stoneking, M and Kessler, O and Schilling, H and Sonanini, A and Conrads, G and Horz, HP}, title = {Global analysis of saliva as a source of bacterial genes for insights into human population structure and migration studies.}, journal = {BMC evolutionary biology}, volume = {14}, number = {}, pages = {190}, pmid = {25183372}, issn = {1471-2148}, mesh = {Bacteria/*classification/genetics/*isolation &amp; purification ; DNA, Bacterial/analysis ; Genes, Bacterial ; Genetic Markers ; Geography ; *Human Migration ; Humans ; Saliva/*microbiology ; }, abstract = {BACKGROUND: The genetic diversity of the human microbiome holds great potential for shedding light on the history of our ancestors. Helicobacter pylori is the most prominent example as its analysis allowed a fine-scale resolution of past migration patterns including some that could not be distinguished using human genetic markers. However studies of H. pylori require stomach biopsies, which severely limits the number of samples that can be analysed. By focussing on the house-keeping gene gdh (coding for the glucose-6-phosphate dehydrogenase), on the virulence gene gtf (coding for the glucosyltransferase) of mitis-streptococci and on the 16S-23S rRNA internal transcribed spacer (ITS) region of the Fusobacterium nucleatum/periodonticum-group we here tested the hypothesis that bacterial genes from human saliva have the potential for distinguishing human populations.<br><br>RESULTS: Analysis of 10 individuals from each of seven geographic regions, encompassing Africa, Asia and Europe, revealed that the genes gdh and ITS exhibited the highest number of polymorphic sites (59% and 79%, respectively) and most OTUs (defined at 99% identity) were unique to a given country. In contrast, the gene gtf had the lowest number of polymorphic sites (21%), and most OTUs were shared among countries. Most of the variation in the gdh and ITS genes was explained by the high clonal diversity within individuals (around 80%) followed by inter-individual variation of around 20%, leaving the geographic region as providing virtually no source of sequence variation. Conversely, for gtf the variation within individuals accounted for 32%, between individuals for 57% and among geographic regions for 11%. This geographic signature persisted upon extension of the analysis to four additional locations from the American continent. Pearson correlation analysis, pairwise Fst-cluster analysis as well as UniFrac analyses consistently supported a tree structure in which the European countries clustered tightly together and branched with American countries and South Africa, to the exclusion of Asian countries and the Congo.<br><br>CONCLUSION: This study shows that saliva harbours protein-coding bacterial genes that are geographically structured, and which could potentially be used for addressing previously unresolved human migration events.}, }
@article {pmid25176148, year = {2014}, author = {Manor, O and Levy, R and Borenstein, E}, title = {Mapping the inner workings of the microbiome: genomic- and metagenomic-based study of metabolism and metabolic interactions in the human microbiome.}, journal = {Cell metabolism}, volume = {20}, number = {5}, pages = {742-752}, pmid = {25176148}, issn = {1932-7420}, support = {DP2 AT007802/AT/NCCIH NIH HHS/United States ; }, mesh = {Bacteria/genetics/metabolism ; Computer Simulation ; Fungi/genetics/metabolism ; Humans ; Metabolic Networks and Pathways ; Metabolome ; *Metabolomics/methods ; Metagenome ; *Metagenomics/methods ; Microbial Interactions ; *Microbiota ; Models, Biological ; }, abstract = {The human gut microbiome is a major contributor to human metabolism and health, yet the metabolic processes that are carried out by various community members, the way these members interact with each other and with the host, and the impact of such interactions on the overall metabolic machinery of the microbiome have not yet been mapped. Here, we discuss recent efforts to study the metabolic inner workings of this complex ecosystem. We will specifically highlight two interrelated lines of work, the first aiming to deconvolve the microbiome and to characterize the metabolic capacity of various microbiome species and the second aiming to utilize computational modeling to infer and study metabolic interactions between these species.}, }
@article {pmid29405744, year = {2014}, author = {Proctor, LM}, title = {Mycins v Microbes Missing Microbes: How the Overuse of Antibiotics Is Fueling Our Modern Plagues by Martin J. Blaser (2014) Holt New York, USA.}, journal = {FASEB journal : official publication of the Federation of American Societies for Experimental Biology}, volume = {28}, number = {9}, pages = {3821-3822}, doi = {10.1096/fj.14-0901ufm}, pmid = {29405744}, issn = {1530-6860}, }
@article {pmid25153520, year = {2014}, author = {Honsa, ES and Maresso, AW and Highlander, SK}, title = {Molecular and evolutionary analysis of NEAr-iron Transporter (NEAT) domains.}, journal = {PloS one}, volume = {9}, number = {8}, pages = {e104794}, pmid = {25153520}, issn = {1932-6203}, support = {A1069697//PHS HHS/United States ; A1097167//PHS HHS/United States ; R21 AI146481/AI/NIAID NIH HHS/United States ; R01 AI097167/AI/NIAID NIH HHS/United States ; R21 AI109465/AI/NIAID NIH HHS/United States ; }, mesh = {Amino Acid Sequence ; Bacterial Proteins/*chemistry/genetics ; Binding Sites ; Gram-Positive Bacteria/*genetics ; Phylogeny ; Protein Structure, Tertiary ; }, abstract = {Iron is essential for bacterial survival, being required for numerous biological processes. NEAr-iron Transporter (NEAT) domains have been studied in pathogenic Gram-positive bacteria to understand how their proteins obtain heme as an iron source during infection. While a 2002 study initially discovered and annotated the NEAT domain encoded by the genomes of several Gram-positive bacteria, there remains a scarcity of information regarding the conservation and distribution of NEAT domains throughout the bacterial kingdom, and whether these domains are restricted to pathogenic bacteria. This study aims to expand upon initial bioinformatics analysis of predicted NEAT domains, by exploring their evolution and conserved function. This information was used to identify new candidate domains in both pathogenic and nonpathogenic organisms. We also searched metagenomic datasets, specifically sequence from the Human Microbiome Project. Here, we report a comprehensive phylogenetic analysis of 343 NEAT domains, encoded by Gram-positive bacteria, mostly within the phylum Firmicutes, with the exception of Eggerthella sp. (Actinobacteria) and an unclassified Mollicutes bacterium (Tenericutes). No new NEAT sequences were identified in the HMP dataset. We detected specific groups of NEAT domains based on phylogeny of protein sequences, including a cluster of novel clostridial NEAT domains. We also identified environmental and soil organisms that encode putative NEAT proteins. Biochemical analysis of heme binding by a NEAT domain from a protein encoded by the soil-dwelling organism Paenibacillus polymyxa demonstrated that the domain is homologous in function to NEAT domains encoded by pathogenic bacteria. Together, this study provides the first global bioinformatics analysis and phylogenetic evidence that NEAT domains have a strong conservation of function, despite group-specific differences at the amino acid level. These findings will provide information useful for future projects concerning the structure and function of NEAT domains, particularly in pathogens where they have yet to be studied.}, }
@article {pmid25148429, year = {2014}, author = {Cui, L and Morris, A and Huang, L and Beck, JM and Twigg, HL and von Mutius, E and Ghedin, E}, title = {The microbiome and the lung.}, journal = {Annals of the American Thoracic Society}, volume = {11 Suppl 4}, number = {Suppl 4}, pages = {S227-32}, pmid = {25148429}, issn = {2325-6621}, support = {K24 HL123342/HL/NHLBI NIH HHS/United States ; U01 HL098962/HL/NHLBI NIH HHS/United States ; U01HL98961/HL/NHLBI NIH HHS/United States ; U01 HL098964/HL/NHLBI NIH HHS/United States ; K24 HL087713/HL/NHLBI NIH HHS/United States ; U01 HL098961/HL/NHLBI NIH HHS/United States ; U01HL098962/HL/NHLBI NIH HHS/United States ; K24HL087713/HL/NHLBI NIH HHS/United States ; U01HL098964/HL/NHLBI NIH HHS/United States ; U01HL098960/HL/NHLBI NIH HHS/United States ; U01 HL098960/HL/NHLBI NIH HHS/United States ; }, mesh = {Humans ; Lung/*microbiology ; Lung Diseases/*microbiology ; *Microbiota ; }, abstract = {Investigation of the human microbiome has become an important field of research facilitated by advances in sequencing technologies. The lung, which is one of the latest body sites being explored for the characterization of human-associated microbial communities, has a microbiome that is suspected to play a substantial role in health and disease. In this review, we provide an overview of the basics of microbiome studies. Challenges in the study of the lung microbiome are highlighted, and further attention is called to the optimization and standardization of methodologies to explore the role of the lung microbiome in health and disease. We also provide examples of lung microbial communities associated with disease or infection status and discuss the role of fungal species in the lung. Finally, we review studies demonstrating that the environmental microbiome can influence lung health and disease, such as the finding that the diversity of microbial exposure correlates inversely with the development of childhood asthma.}, }
@article {pmid25136443, year = {2014}, author = {Wu, YW and Tang, YH and Tringe, SG and Simmons, BA and Singer, SW}, title = {MaxBin: an automated binning method to recover individual genomes from metagenomes using an expectation-maximization algorithm.}, journal = {Microbiome}, volume = {2}, number = {}, pages = {26}, pmid = {25136443}, issn = {2049-2618}, abstract = {BACKGROUND: Recovering individual genomes from metagenomic datasets allows access to uncultivated microbial populations that may have important roles in natural and engineered ecosystems. Understanding the roles of these uncultivated populations has broad application in ecology, evolution, biotechnology and medicine. Accurate binning of assembled metagenomic sequences is an essential step in recovering the genomes and understanding microbial functions.<br><br>RESULTS: We have developed a binning algorithm, MaxBin, which automates the binning of assembled metagenomic scaffolds using an expectation-maximization algorithm after the assembly of metagenomic sequencing reads. Binning of simulated metagenomic datasets demonstrated that MaxBin had high levels of accuracy in binning microbial genomes. MaxBin was used to recover genomes from metagenomic data obtained through the Human Microbiome Project, which demonstrated its ability to recover genomes from real metagenomic datasets with variable sequencing coverages. Application of MaxBin to metagenomes obtained from microbial consortia adapted to grow on cellulose allowed genomic analysis of new, uncultivated, cellulolytic bacterial populations, including an abundant myxobacterial population distantly related to Sorangium cellulosum that possessed a much smaller genome (5&#xa0;MB versus 13 to 14&#xa0;MB) but has a more extensive set of genes for biomass deconstruction. For the cellulolytic consortia, the MaxBin results were compared to binning using emergent self-organizing maps (ESOMs) and differential coverage binning, demonstrating that it performed comparably to these methods but had distinct advantages in automation, resolution of related genomes and sensitivity.<br><br>CONCLUSIONS: The automatic binning software that we developed successfully classifies assembled sequences in metagenomic datasets into recovered individual genomes. The isolation of dozens of species in cellulolytic microbial consortia, including a novel species of myxobacteria that has the smallest genome among all sequenced aerobic myxobacteria, was easily achieved using the binning software. This work demonstrates that the processes required for recovering genomes from assembled metagenomic datasets can be readily automated, an important advance in understanding the metabolic potential of microbes in natural environments. MaxBin is available at https://sourceforge.net/projects/maxbin/.}, }
@article {pmid25133738, year = {2014}, author = {Dinakaran, V and Rathinavel, A and Pushpanathan, M and Sivakumar, R and Gunasekaran, P and Rajendhran, J}, title = {Elevated levels of circulating DNA in cardiovascular disease patients: metagenomic profiling of microbiome in the circulation.}, journal = {PloS one}, volume = {9}, number = {8}, pages = {e105221}, pmid = {25133738}, issn = {1932-6203}, mesh = {Actinobacteria/genetics ; Adolescent ; Adult ; Cardiovascular Diseases/*blood/microbiology/virology ; DNA/*blood ; DNA, Bacterial/blood/genetics ; DNA, Viral/blood/genetics ; Female ; Humans ; Male ; Metagenomics ; Middle Aged ; Propionibacterium/genetics ; Proteobacteria/genetics ; Pseudomonas Phages/genetics ; RNA, Ribosomal, 16S/blood/genetics ; Young Adult ; beta-Globins/genetics ; }, abstract = {Cardiovascular diseases (CVDs) are the leading cause of death worldwide. An expanding body of evidence supports the role of human microbiome in the establishment of CVDs and, this has gained much attention recently. This work was aimed to study the circulating human microbiome in CVD patients and healthy subjects. The levels of circulating cell free DNA (circDNA) was higher in CVD patients (n = 80) than in healthy controls (n = 40). More specifically, the relative levels of circulating bacterial DNA and the ratio of 16S rRNA/β-globin gene copy numbers were higher in the circulation of CVD patients than healthy individuals. In addition, we found a higher circulating microbial diversity in CVD patients (n = 3) in comparison to healthy individuals (n = 3) by deep shotgun sequencing. At the phylum level, we observed a dominance of Actinobacteria in CVD patients, followed by Proteobacteria, in contrast to that in healthy controls, where Proteobacteria was predominantly enriched, followed by Actinobacteria. The circulating virome in CVD patients was enriched with bacteriophages with a preponderance of Propionibacterium phages, followed by Pseudomonas phages and Rhizobium phages in contrast to that in healthy individuals, where a relatively greater abundance of eukaryotic viruses dominated by Lymphocystis virus (LCV) and Torque Teno viruses (TTV) was observed. Thus, the release of bacterial and viral DNA elements in the circulation could play a major role leading to elevated circDNA levels in CVD patients. The increased circDNA levels could be either the cause or consequence of CVD incidence, which needs to be explored further.}, }
@article {pmid25127240, year = {2014}, author = {Bisanz, JE and Seney, S and McMillan, A and Vongsa, R and Koenig, D and Wong, L and Dvoracek, B and Gloor, GB and Sumarah, M and Ford, B and Herman, D and Burton, JP and Reid, G}, title = {A systems biology approach investigating the effect of probiotics on the vaginal microbiome and host responses in a double blind, placebo-controlled clinical trial of post-menopausal women.}, journal = {PloS one}, volume = {9}, number = {8}, pages = {e104511}, pmid = {25127240}, issn = {1932-6203}, mesh = {Administration, Intravaginal ; Adult ; Aged ; Aged, 80 and over ; Double-Blind Method ; Female ; Humans ; Limosilactobacillus reuteri/growth &amp; development/*metabolism ; Lacticaseibacillus rhamnosus/growth &amp; development/*metabolism ; Microbiota/physiology ; Middle Aged ; Placebos ; Postmenopause ; Probiotics/*therapeutic use ; RNA, Ribosomal, 16S/genetics ; Systems Biology/methods ; Tight Junctions/physiology ; Toll-Like Receptor 2/metabolism ; Treatment Outcome ; Vagina/*microbiology ; Vaginosis, Bacterial/microbiology/*therapy ; }, abstract = {UNLABELLED: A lactobacilli dominated microbiota in most pre and post-menopausal women is an indicator of vaginal health. The objective of this double blinded, placebo-controlled crossover study was to evaluate in 14 post-menopausal women with an intermediate Nugent score, the effect of 3 days of vaginal administration of probiotic L. rhamnosus GR-1 and L. reuteri RC-14 (2.5×109 CFU each) on the microbiota and host response. The probiotic treatment did not result in an improved Nugent score when compared to when placebo. Analysis using 16S rRNA sequencing and metabolomics profiling revealed that the relative abundance of Lactobacillus was increased following probiotic administration as compared to placebo, which was weakly associated with an increase in lactate levels. A decrease in Atopobium was also observed. Analysis of host responses by microarray showed the probiotics had an immune-modulatory response including effects on pattern recognition receptors such as TLR2 while also affecting epithelial barrier function. This is the first study to use an interactomic approach for the study of vaginal probiotic administration in post-menopausal women. It shows that in some cases multifaceted approaches are required to detect the subtle molecular changes induced by the host to instillation of probiotic strains.<br><br>TRIAL REGISTRATION: ClinicalTrials.gov NCT02139839.}, }
@article {pmid25120956, year = {2014}, author = {McLean, JS}, title = {Advancements toward a systems level understanding of the human oral microbiome.}, journal = {Frontiers in cellular and infection microbiology}, volume = {4}, number = {}, pages = {98}, pmid = {25120956}, issn = {2235-2988}, support = {R01 DE020102/DE/NIDCR NIH HHS/United States ; }, mesh = {Bacteria/classification/genetics/metabolism ; Bacterial Physiological Phenomena ; Biofilms ; Datasets as Topic ; Dental Plaque/microbiology ; Host-Pathogen Interactions ; Humans ; Hydrogen-Ion Concentration ; *Metagenome ; Metagenomics ; Microbial Interactions ; *Microbiota ; Mouth/*microbiology ; Phylogeny ; Tooth Demineralization/etiology ; }, abstract = {Oral microbes represent one of the most well studied microbial communities owing to the fact that they are a fundamental part of human development influencing health and disease, an easily accessible human microbiome, a highly structured and remarkably resilient biofilm as well as a model of bacteria-bacteria and bacteria-host interactions. In the last 80 years since oral plaque was first characterized for its functionally stable physiological properties such as the highly repeatable rapid pH decrease upon carbohydrate addition and subsequent recovery phase, the fundamental approaches to study the oral microbiome have cycled back and forth between community level investigations and characterizing individual model isolates. Since that time, many individual species have been well characterized and the development of the early plaque community, which involves many cell-cell binding interactions, has been carefully described. With high throughput sequencing enabling the enormous diversity of the oral cavity to be realized, a number of new challenges to progress were revealed. The large number of uncultivated oral species, the high interpersonal variability of taxonomic carriage and the possibility of multiple pathways to dysbiosis pose as major hurdles to obtain a systems level understanding from the community to the gene level. It is now possible however to start connecting the insights gained from single species with community wide approaches. This review will discuss some of the recent insights into the oral microbiome at a fundamental level, existing knowledge gaps, as well as challenges that have surfaced and the approaches to address them.}, }
@article {pmid25118239, year = {2014}, author = {Eilam, O and Zarecki, R and Oberhardt, M and Ursell, LK and Kupiec, M and Knight, R and Gophna, U and Ruppin, E}, title = {Glycan degradation (GlyDeR) analysis predicts mammalian gut microbiota abundance and host diet-specific adaptations.}, journal = {mBio}, volume = {5}, number = {4}, pages = {}, pmid = {25118239}, issn = {2150-7511}, support = {T32 GM008759/GM/NIGMS NIH HHS/United States ; T32 GM142607/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Bacteria/*metabolism ; *Diet ; Gastrointestinal Tract/*microbiology ; Genomics ; Humans ; Linear Models ; Metagenomics ; *Microbiota ; Polysaccharides/*metabolism ; Prebiotics ; }, abstract = {UNLABELLED: Glycans form the primary nutritional source for microbes in the human gut, and understanding their metabolism is a critical yet understudied aspect of microbiome research. Here, we present a novel computational pipeline for modeling glycan degradation (GlyDeR) which predicts the glycan degradation potency of 10,000 reference glycans based on either genomic or metagenomic data. We first validated GlyDeR by comparing degradation profiles for genomes in the Human Microbiome Project against KEGG reaction annotations. Next, we applied GlyDeR to the analysis of human and mammalian gut microbial communities, which revealed that the glycan degradation potential of a community is strongly linked to host diet and can be used to predict diet with higher accuracy than sequence data alone. Finally, we show that a microbe's glycan degradation potential is significantly correlated (R = 0.46) with its abundance, with even higher correlations for potential pathogens such as the class Clostridia (R = 0.76). GlyDeR therefore represents an important tool for advancing our understanding of bacterial metabolism in the gut and for the future development of more effective prebiotics for microbial community manipulation.<br><br>IMPORTANCE: The increased availability of high-throughput sequencing data has positioned the gut microbiota as a major new focal point for biomedical research. However, despite the expenditure of huge efforts and resources, sequencing-based analysis of the microbiome has uncovered mostly associative relationships between human health and diet, rather than a causal, mechanistic one. In order to utilize the full potential of systems biology approaches, one must first characterize the metabolic requirements of gut bacteria, specifically, the degradation of glycans, which are their primary nutritional source. We developed a computational framework called GlyDeR for integrating expert knowledge along with high-throughput data to uncover important new relationships within glycan metabolism. GlyDeR analyzes particular bacterial (meta)genomes and predicts the potency by which they degrade a variety of different glycans. Based on GlyDeR, we found a clear connection between microbial glycan degradation and human diet, and we suggest a method for the rational design of novel prebiotics.}, }
@article {pmid25102857, year = {2015}, author = {Matsen, FA}, title = {Phylogenetics and the human microbiome.}, journal = {Systematic biology}, volume = {64}, number = {1}, pages = {e26-41}, pmid = {25102857}, issn = {1076-836X}, support = {R01 HG005966/HG/NHGRI NIH HHS/United States ; R01-HG005966-01/HG/NHGRI NIH HHS/United States ; }, mesh = {Bacteria/genetics ; Humans ; Microbiota/genetics ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; }, abstract = {The human microbiome is the ensemble of genes in the microbes that live inside and on the surface of humans. Because microbial sequencing information is now much easier to come by than phenotypic information, there has been an explosion of sequencing and genetic analysis of microbiome samples. Much of the analytical work for these sequences involves phylogenetics, at least indirectly, but methodology has developed in a somewhat different direction than for other applications of phylogenetics. In this article, I review the field and its methods from the perspective of a phylogeneticist, as well as describing current challenges for phylogenetics coming from this type of work.}, }
@article {pmid25102107, year = {2014}, author = {Daley, D}, title = {The evolution of the hygiene hypothesis: the role of early-life exposures to viruses and microbes and their relationship to asthma and allergic diseases.}, journal = {Current opinion in allergy and clinical immunology}, volume = {14}, number = {5}, pages = {390-396}, doi = {10.1097/ACI.0000000000000101}, pmid = {25102107}, issn = {1473-6322}, mesh = {Airway Remodeling ; Asthma/etiology/*immunology ; Bacteria/*immunology ; Environmental Exposure/adverse effects ; Gene-Environment Interaction ; Host-Pathogen Interactions ; Humans ; *Hygiene Hypothesis ; Hypersensitivity/etiology/*immunology ; Immunity, Mucosal ; Infant ; Infant, Newborn ; Infections/complications/*immunology ; Microbiota ; Viruses/*immunology ; }, abstract = {PURPOSE OF REVIEW: Understanding the mechanisms involved in the development of asthma and allergic diseases is expanding, due in part to sequencing advances that have led to the identification of new viral strains such as human rhinovirus strain C (HRV-C) and the human microbiome project.<br><br>RECENT FINDINGS: Recent studies have identified new ways in which viral and microbial exposures in early life interact with host genetic background/variants to modify the risk for developing asthma and allergic diseases. Recent research suggests that HRV-C is the main pathogenic agent associated with infant wheeze, hospitalizations and likely the subsequent development of asthma. Pulmonary He MRI suggests that HRV infection in early childhood and subsequent immune responses initiate airway remodeling. Numerous studies of the microbiome indicate that intestinal and airway microbiome diversity and composition contribute to the cause of asthma and allergic diseases.<br><br>SUMMARY: Susceptibility to asthma and allergic diseases is complex and involves genetic variants and environmental exposures (bacteria, viruses, smoking, and pet ownership), alteration of our microbiome and potentially large-scale manipulation of the environment over the past century.}, }
@article {pmid25101067, year = {2014}, author = {Leonard, MT and Davis-Richardson, AG and Ardissone, AN and Kemppainen, KM and Drew, JC and Ilonen, J and Knip, M and Simell, O and Toppari, J and Veijola, R and Hyöty, H and Triplett, EW}, title = {The methylome of the gut microbiome: disparate Dam methylation patterns in intestinal Bacteroides dorei.}, journal = {Frontiers in microbiology}, volume = {5}, number = {}, pages = {361}, pmid = {25101067}, issn = {1664-302X}, abstract = {Despite the large interest in the human microbiome in recent years, there are no reports of bacterial DNA methylation in the microbiome. Here metagenomic sequencing using the Pacific Biosciences platform allowed for rapid identification of bacterial GATC methylation status of a bacterial species in human stool samples. For this work, two stool samples were chosen that were dominated by a single species, Bacteroides dorei. Based on 16S rRNA analysis, this species represented over 45% of the bacteria present in these two samples. The B. dorei genome sequence from these samples was determined and the GATC methylation sites mapped. The Bacteroides dorei genome from one subject lacked any GATC methylation and lacked the DNA adenine methyltransferase genes. In contrast, B. dorei from another subject contained 20,551 methylated GATC sites. Of the 4970 open reading frames identified in the GATC methylated B. dorei genome, 3184 genes were methylated as well as 1735 GATC methylations in intergenic regions. These results suggest that DNA methylation patterns are important to consider in multi-omic analyses of microbiome samples seeking to discover the diversity of bacterial functions and may differ between disease states.}, }
@article {pmid25091187, year = {2014}, author = {Can, I and Javan, GT and Pozhitkov, AE and Noble, PA}, title = {Distinctive thanatomicrobiome signatures found in the blood and internal organs of humans.}, journal = {Journal of microbiological methods}, volume = {106}, number = {}, pages = {1-7}, doi = {10.1016/j.mimet.2014.07.026}, pmid = {25091187}, issn = {1872-8359}, mesh = {Adult ; Aged ; Blood/*microbiology ; Brain/*microbiology ; *Cadaver ; Cluster Analysis ; DNA, Ribosomal/chemistry/genetics ; Heart/*microbiology ; Humans ; Liver/*microbiology ; Male ; *Microbiota ; Middle Aged ; Molecular Sequence Data ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; Spleen/*microbiology ; Young Adult ; }, abstract = {According to the Human Microbiome Project, 90% of the cells in a healthy adult body are microorganisms. What happens to these cells after human host death, defined here as the thanatomicrobiome (i.e., thanatos-, Greek defn., death), is not clear. To fill the void, we examined the thanatomicrobiome of the spleen, liver, brain, heart and blood of human cadavers. These organs are thought to be devoid of microorganisms in a healthy adult host. We report that the thanatomicrobiome was highly similar among organ tissues from the same cadaver but very different among the cadavers possibly due to differences in the elapsed time since death and/or environmental factors. Isolation of microbial DNA from cadavers is known to be a challenge. We compared the effectiveness of two methods by amplifying the 16S rRNA genes and sequencing the amplicons from four cadavers. Paired comparisons revealed that the conventional DNA extraction method (bead-beating in phenol/chloroform/bead-beating followed by ethanol precipitation) yielded more 16S rRNA amplicons (28 of 30 amplicons) than a second method (repeated cycles of heating/cooling followed by centrifugation to remove cellular debris) (19 of 30 amplicons). Shannon diversity index of the 16S rRNA genes revealed no significant difference by extraction method. The present report provides a proof of principle that the thanatomicrobiome may be an efficient biomarker to study postmortem transformations of cadavers.}, }
@article {pmid25083877, year = {2014}, author = {González, A and Vázquez-Baeza, Y and Knight, R}, title = {SnapShot: the human microbiome.}, journal = {Cell}, volume = {158}, number = {3}, pages = {690-690.e1}, doi = {10.1016/j.cell.2014.07.019}, pmid = {25083877}, issn = {1097-4172}, support = {//Howard Hughes Medical Institute/United States ; }, mesh = {Child, Preschool ; Female ; Humans ; Infant ; Infant, Newborn ; Inflammatory Bowel Diseases/microbiology ; *Microbiota ; Obesity/microbiology ; Organ Specificity ; Pregnancy ; }, }
@article {pmid25082158, year = {2014}, author = {Klaus, HD}, title = {Frontiers in the bioarchaeology of stress and disease: cross-disciplinary perspectives from pathophysiology, human biology, and epidemiology.}, journal = {American journal of physical anthropology}, volume = {155}, number = {2}, pages = {294-308}, doi = {10.1002/ajpa.22574}, pmid = {25082158}, issn = {1096-8644}, mesh = {Archaeology/*methods ; *Disease ; *Epidemiologic Methods ; Epigenomics ; Humans ; Inflammation ; Microbiota ; Paleopathology/*methods ; Periostitis ; Signal Transduction ; *Stress, Physiological ; }, abstract = {Over the last four decades, bioarchaeology has experienced significant technical growth and theoretical maturation. Early 21st century bioarchaeology may also be enhanced from a renewed engagement with the concept of biological stress. New insights on biological stress and disease can be gained from cross-disciplinary perspectives regarding human skeletal variation and disease. First, pathophysiologic and molecular signaling mechanisms can provide more precise understandings regarding formation of pathological phenotypes in bone. Using periosteal new bone formation as an example, various mechanisms and pathways are explored in which new bone can be formed under conditions of biological stress, particularly in bone microenvironments that involve inflammatory changes. Second, insights from human biology are examined regarding some epigenetic factors and disease etiology. While epigenetic effects on stress and disease outcomes appear profoundly influential, they are mostly invisible in skeletal tissue. However, some indirect and downstream effects, such as the developmental origins of adult health outcomes, may be partially observable in bioarchaeological data. Emerging perspectives from the human microbiome are also considered. Microbiomics involves a remarkable potential to understand ancient biology, disease, and stress. Third, tools from epidemiology are examined that may aid bioarchaeologists to better cope with some of the inherent limitations of skeletal samples to better measure and quantify the expressions of skeletal stress markers. Such cross-disciplinary synergisms hopefully will promote more complete understandings of health and stress in bioarchaeological science.}, }
@article {pmid25079685, year = {2015}, author = {Claesen, J and Fischbach, MA}, title = {Synthetic microbes as drug delivery systems.}, journal = {ACS synthetic biology}, volume = {4}, number = {4}, pages = {358-364}, pmid = {25079685}, issn = {2161-5063}, support = {R01 AI101018/AI/NIAID NIH HHS/United States ; DP2 OD007290/OD/NIH HHS/United States ; AI101018/AI/NIAID NIH HHS/United States ; R21 AI101722/AI/NIAID NIH HHS/United States ; GM081879/GM/NIGMS NIH HHS/United States ; AI101722/AI/NIAID NIH HHS/United States ; P50 GM081879/GM/NIGMS NIH HHS/United States ; OD007290/OD/NIH HHS/United States ; }, mesh = {Animals ; *Bacteria ; Cell Engineering/*methods ; Drug Delivery Systems/*methods ; Humans ; Synthetic Biology/methods ; }, abstract = {Synthetic cell therapy is a field that has broad potential for future applications in human disease treatment. Next generation therapies will consist of engineered bacterial strains capable of diagnosing disease, producing and delivering therapeutics, and controlling their numbers to meet containment and safety concerns. A thorough understanding of the microbial ecology of the human body and the interaction of the microbes with the immune system will benefit the choice of an appropriate chassis that engrafts stably and interacts productively with the resident community in specific body niches.}, }
@article {pmid25073854, year = {2014}, author = {Fettweis, JM and Brooks, JP and Serrano, MG and Sheth, NU and Girerd, PH and Edwards, DJ and Strauss, JF and The Vaginal Microbiome Consortium,  and Jefferson, KK and Buck, GA}, title = {Differences in vaginal microbiome in African American women versus women of European ancestry.}, journal = {Microbiology (Reading, England)}, volume = {160}, number = {Pt 10}, pages = {2272-2282}, pmid = {25073854}, issn = {1465-2080}, support = {4UH3AI083263/AI/NIAID NIH HHS/United States ; P60 MD002256/MD/NIMHD NIH HHS/United States ; U54 HD080784/HD/NICHD NIH HHS/United States ; UH3 AI083263/AI/NIAID NIH HHS/United States ; U54 DE023786/DE/NIDCR NIH HHS/United States ; }, mesh = {Black or African American ; DNA, Bacterial/chemistry/genetics ; DNA, Ribosomal/chemistry/genetics ; Female ; Humans ; *Microbiota ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; Vagina/*microbiology ; Virginia ; White People ; }, abstract = {Women of European ancestry are more likely to harbour a Lactobacillus-dominated microbiome, whereas African American women are more likely to exhibit a diverse microbial profile. African American women are also twice as likely to be diagnosed with bacterial vaginosis and are twice as likely to experience preterm birth. The objective of this study was to further characterize and contrast the vaginal microbial profiles in African American versus European ancestry women. Through the Vaginal Human Microbiome Project at Virginia Commonwealth University, 16S rRNA gene sequence analysis was used to compare the microbiomes of vaginal samples from 1268 African American women and 416 women of European ancestry. The results confirmed significant differences in the vaginal microbiomes of the two groups and identified several taxa relevant to these differences. Major community types were dominated by Gardnerella vaginalis and the uncultivated bacterial vaginosis-associated bacterium-1 (BVAB1) that were common among African Americans. Moreover, the prevalence of multiple bacterial taxa that are associated with microbial invasion of the amniotic cavity and preterm birth, including Mycoplasma, Gardnerella, Prevotella and Sneathia, differed between the two ethnic groups. We investigated the contributions of intrinsic and extrinsic factors, including pregnancy, body mass index, diet, smoking and alcohol use, number of sexual partners, and household income, to vaginal community composition. Ethnicity, pregnancy and alcohol use correlated significantly with the relative abundance of bacterial vaginosis-associated species. Trends between microbial profiles and smoking and number of sexual partners were observed; however, these associations were not statistically significant. These results support and extend previous findings that there are significant differences in the vaginal microbiome related to ethnicity and demonstrate that these differences are pronounced even in healthy women.}, }
@article {pmid25071997, year = {2014}, author = {Colehour, AM and Meadow, JF and Liebert, MA and Cepon-Robins, TJ and Gildner, TE and Urlacher, SS and Bohannan, BJ and Snodgrass, JJ and Sugiyama, LS}, title = {Local domestication of lactic acid bacteria via cassava beer fermentation.}, journal = {PeerJ}, volume = {2}, number = {}, pages = {e479}, pmid = {25071997}, issn = {2167-8359}, abstract = {Cassava beer, or chicha, is typically consumed daily by the indigenous Shuar people of the Ecuadorian Amazon. This traditional beverage made from cassava tuber (Manihot esculenta) is thought to improve nutritional quality and flavor while extending shelf life in a tropical climate. Bacteria responsible for chicha fermentation could be a source of microbes for the human microbiome, but little is known regarding the microbiology of chicha. We investigated bacterial community composition of chicha batches using Illumina high-throughput sequencing. Fermented chicha samples were collected from seven Shuar households in two neighboring villages in the Morona-Santiago region of Ecuador, and the composition of the bacterial communities within each chicha sample was determined by sequencing a region of the 16S ribosomal gene. Members of the genus Lactobacillus dominated all samples. Significantly greater phylogenetic similarity was observed among chicha samples taken within a village than those from different villages. Community composition varied among chicha samples, even those separated by short geographic distances, suggesting that ecological and/or evolutionary processes, including human-mediated factors, may be responsible for creating locally distinct ferments. Our results add to evidence from other fermentation systems suggesting that traditional fermentation may be a form of domestication, providing endemic beneficial inocula for consumers, but additional research is needed to identify the mechanisms and extent of microbial dispersal.}, }
@article {pmid25066330, year = {2014}, author = {Stokholm, J and Sevelsted, A and Bønnelykke, K and Bisgaard, H}, title = {Maternal propensity for infections and risk of childhood asthma: a registry-based cohort study.}, journal = {The Lancet. Respiratory medicine}, volume = {2}, number = {8}, pages = {631-637}, doi = {10.1016/S2213-2600(14)70152-3}, pmid = {25066330}, issn = {2213-2619}, mesh = {Administration, Inhalation ; Adolescent ; Adrenal Cortex Hormones/administration &amp; dosage ; Adult ; Ambulatory Care/statistics &amp; numerical data ; Anti-Bacterial Agents/*therapeutic use ; Asthma/chemically induced/drug therapy/*epidemiology ; Child ; Child, Preschool ; Denmark/epidemiology ; Disease Susceptibility ; Dose-Response Relationship, Drug ; Drug Prescriptions/statistics &amp; numerical data ; Female ; Hospitalization/statistics &amp; numerical data ; Humans ; Incidence ; Infant ; Infant, Newborn ; Mothers/*statistics &amp; numerical data ; Postnatal Care/statistics &amp; numerical data ; Preconception Care/statistics &amp; numerical data ; Pregnancy ; Pregnancy Complications, Infectious/*drug therapy ; Pregnancy Trimesters ; Prenatal Care/statistics &amp; numerical data ; Prenatal Exposure Delayed Effects/chemically induced/drug therapy/*epidemiology ; Prospective Studies ; Registries ; Time Factors ; Young Adult ; }, abstract = {BACKGROUND: Maternal use of antibiotics during pregnancy has been associated with the development of asthmatic disorders in the offspring. The human microbiome has been suggested to act as an intermediary in this process. To provide clarification on this theory, we studied the temporal relation between maternal use of antibiotics and the risk of childhood asthma.<br><br>METHODS: According to national registries, during the observation period (1997-2010), 910,301 children were born in Denmark and were included in the analysis. From these registries, data for cases of childhood asthma were obtained based on hospital admissions, outpatient attendance at a hospital, or use of inhaled corticosteroids. The effect of timing of maternal antibiotic use on the risk of asthma in the offspring was studied by analysis of maternal antibiotic use in the 80 weeks before pregnancy, during pregnancy, and the 80 weeks after pregnancy. Results were adjusted for age and calendar year, birthweight, gestational age, sex, mode of delivery, parity, multiple births, season of birth, and several maternal factors (age, smoking during pregnancy, employment status, and asthma).<br><br>FINDINGS: In this study, we replicated our previous finding that maternal use of antibiotics in pregnancy was associated with an increased risk of childhood asthma: the adjusted incidence rate ratio (aIRR) was 1&#xb7;24 (95% CI 1&#xb7;18-1&#xb7;30) for inpatient admission, 1&#xb7;22 (1&#xb7;18-1&#xb7;26) for outpatient attendance, and 1&#xb7;18 (1&#xb7;15-1&#xb7;20) for inhaled corticosteroid use. A similar and independent association was also recorded for maternal antibiotic use in the 80 weeks before and after the pregnancy. A dose-related association occurred between the risk of childhood asthma and the number of maternal antibiotic treatments and was recorded separately for antibiotic treatment for respiratory tract infections and for other types of infections.<br><br>INTERPRETATION: Maternal use of antibiotics has a dose-related association with the risk of asthma in the offspring, but this association is independent of the temporal relationship with the pregnancy period. This finding suggests that maternal antibiotic use is a surrogate marker of a mother's general propensity for infections as the underlying link between a mother's use of antibiotics and risk of asthma in the offspring.<br><br>FUNDING: The Danish Council for Strategic Research, The Lundbeck Foundation, The Pharmacy Foundation of 1991, the Danish Medical Research Council, and National Finance Act.}, }
@article {pmid25052396, year = {2014}, author = {Aujoulat, F and Bouvet, P and Jumas-Bilak, E and Jean-Pierre, H and Marchandin, H}, title = {Veillonella seminalis sp. nov., a novel anaerobic Gram-stain-negative coccus from human clinical samples, and emended description of the genus Veillonella.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {64}, number = {Pt 10}, pages = {3526-3531}, doi = {10.1099/ijs.0.064451-0}, pmid = {25052396}, issn = {1466-5034}, mesh = {Abscess/*microbiology ; Adolescent ; Adult ; Child ; Child, Preschool ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Female ; Genes, Bacterial ; Humans ; Infant ; Male ; Middle Aged ; Molecular Sequence Data ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Semen/*microbiology ; Sequence Analysis, DNA ; Veillonella/*classification/genetics/isolation &amp; purification ; Young Adult ; }, abstract = {Ten isolates of unknown, Gram-stain-negative, anaerobic cocci were recovered from human clinical samples, mainly from semen. On the basis of their phenotypic features, including morphology, main metabolic end products, gas production, nitrate reduction and decarboxylation of succinate, the strains were identified as members of the genus Veillonella. Multi-locus sequence analysis and corresponding phylogenies were based on 16S rRNA, dnaK and rpoB genes, and on the newly proposed gltA gene. The strains shared high levels of genetic sequence similarity and were related most closely to Veillonella ratti. The strains could not be differentiated from V. ratti on the basis of 16S rRNA gene sequence analysis while gltA, rpoB and dnaK gene sequences showed 85.1, 93.5 and 90.2% similarity with those of the type strain of V. ratti, respectively. Phylogenetic analyses revealed that the isolates formed a robust clade in the V. ratti-Veillonella criceti-Veillonella magna subgroup of the genus Veillonella. As observed for V. criceti, the isolates were able to ferment fructose. In contrast to other members of the genus Veillonella, the 10 strains were not able to metabolize lactate. Cellular fatty acid composition was consistent with that of other species of the genus Veillonella. From these data, the 10 isolates are considered to belong to a novel species in the genus Veillonella, for which the name Veillonella seminalis sp. nov. is proposed. The type strain is ADV 4313.2(T) (= CIP 107810(T) = LMG 28162(T)). Veillonella strain ACS-216-V-Col6b subjected to whole genome sequencing as part as the Human Microbiome Project is another representative of V. seminalis sp. nov. An emended description of the genus Veillonella is also proposed.}, }
@article {pmid25036628, year = {2014}, author = {Goodrich, JK and Di Rienzi, SC and Poole, AC and Koren, O and Walters, WA and Caporaso, JG and Knight, R and Ley, RE}, title = {Conducting a microbiome study.}, journal = {Cell}, volume = {158}, number = {2}, pages = {250-262}, pmid = {25036628}, issn = {1097-4172}, support = {P01 DK078669/DK/NIDDK NIH HHS/United States ; R01 MD011389/MD/NIMHD NIH HHS/United States ; T32 GM008759/GM/NIGMS NIH HHS/United States ; R01 HG004872/HG/NHGRI NIH HHS/United States ; T32 GM142607/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Archaea/classification/genetics/isolation &amp; purification ; Bacteria/classification/genetics/isolation &amp; purification ; Guidelines as Topic ; Humans ; *Microbiological Techniques ; *Microbiota ; Polymerase Chain Reaction ; Ribotyping ; }, abstract = {Human microbiome research is an actively developing area of inquiry, with ramifications for our lifestyles, our interactions with microbes, and how we treat disease. Advances depend on carefully executed, controlled, and reproducible studies. Here, we provide a Primer for researchers from diverse disciplines interested in conducting microbiome research. We discuss factors to be considered in the design, execution, and data analysis of microbiome studies. These recommendations should help researchers to enter and contribute to this rapidly developing field.}, }
@article {pmid25024916, year = {2014}, author = {Meadow, JF and Altrichter, AE and Green, JL}, title = {Mobile phones carry the personal microbiome of their owners.}, journal = {PeerJ}, volume = {2}, number = {}, pages = {e447}, pmid = {25024916}, issn = {2167-8359}, abstract = {Most people on the planet own mobile phones, and these devices are increasingly being utilized to gather data relevant to our personal health, behavior, and environment. During an educational workshop, we investigated the utility of mobile phones to gather data about the personal microbiome - the collection of microorganisms associated with the personal effects of an individual. We characterized microbial communities on smartphone touchscreens to determine whether there was significant overlap with the skin microbiome sampled directly from their owners. We found that about 22% of the bacterial taxa on participants' fingers were also present on their own phones, as compared to 17% they shared on average with other people's phones. When considered as a group, bacterial communities on men's phones were significantly different from those on their fingers, while women's were not. Yet when considered on an individual level, men and women both shared significantly more of their bacterial communities with their own phones than with anyone else's. In fact, 82% of the OTUs were shared between a person's index and phone when considering the dominant taxa (OTUs with more than 0.1% of the sequences in an individual's dataset). Our results suggest that mobile phones hold untapped potential as personal microbiome sensors.}, }
@article {pmid25020228, year = {2014}, author = {Abeles, SR and Pride, DT}, title = {Molecular bases and role of viruses in the human microbiome.}, journal = {Journal of molecular biology}, volume = {426}, number = {23}, pages = {3892-3906}, pmid = {25020228}, issn = {1089-8638}, support = {K08 AI085028/AI/NIAID NIH HHS/United States ; }, mesh = {Bacteriophages/*growth &amp; development ; *Ecosystem ; Humans ; *Microbiota ; }, abstract = {Viruses are dependent biological entities that interact with the genetic material of most cells on the planet, including the trillions within the human microbiome. Their tremendous diversity renders analysis of human viral communities ("viromes") to be highly complex. Because many of the viruses in humans are bacteriophage, their dynamic interactions with their cellular hosts add greatly to the complexities observed in examining human microbial ecosystems. We are only beginning to be able to study human viral communities on a large scale, mostly as a result of recent and continued advancements in sequencing and bioinformatic technologies. Bacteriophage community diversity in humans not only is inexorably linked to the diversity of their cellular hosts but also is due to their rapid evolution, horizontal gene transfers, and intimate interactions with host nucleic acids. There are vast numbers of observed viral genotypes on many body surfaces studied, including the oral, gastrointestinal, and respiratory tracts, and even in the human bloodstream, which previously was considered a purely sterile environment. The presence of viruses in blood suggests that virome members can traverse mucosal barriers, as indeed these communities are substantially altered when mucosal defenses are weakened. Perhaps the most interesting aspect of human viral communities is the extent to which they can carry gene functions involved in the pathogenesis of their hosts, particularly antibiotic resistance. Persons in close contact with each other have been shown to share a fraction of oral virobiota, which could potentially have important implications for the spread of antibiotic resistance to healthy individuals. Because viruses can have a large impact on ecosystem dynamics through mechanisms such as the transfers of beneficial gene functions or the lysis of certain populations of cellular hosts, they may have both beneficial and detrimental roles that affect human health, including improvements in microbial resilience to disturbances, immune evasion, maintenance of physiologic processes, and altering the microbial community in ways that promote or prevent pathogen colonization.}, }
@article {pmid25013912, year = {2014}, author = {Jones, ML and Ganopolsky, JG and Martoni, CJ and Labbé, A and Prakash, S}, title = {Emerging science of the human microbiome.}, journal = {Gut microbes}, volume = {5}, number = {4}, pages = {446-457}, doi = {10.4161/gmic.29810}, pmid = {25013912}, issn = {1949-0984}, mesh = {Communicable Diseases/*microbiology ; *Health ; *Host-Pathogen Interactions ; Humans ; Metagenomics/*trends ; Microbiology/*trends ; *Microbiota ; }, abstract = {The human gastrointestinal tract hosts a large number of microbial cells which exceed their mammalian counterparts by approximately 3-fold. The genes expressed by these microorganisms constitute the gut microbiome and may participate in diverse functions that are essential to the host, including digestion, regulation of energy metabolism, and modulation of inflammation and immunity. The gut microbiome can be modulated by dietary changes, antibiotic use, or disease. Different ailments have distinct associated microbiomes in which certain species or genes are present in different relative quantities. Thus, identifying specific disease-associated signatures in the microbiome as well as the factors that alter microbial populations and gene expression will lead to the development of new products such as prebiotics, probiotics, antimicrobials, live biotherapeutic products, or more traditional drugs to treat these disorders. Gained knowledge on the microbiome may result in molecular lab tests that may serve as personalized tools to guide the use of the aforementioned products and monitor interventional progress.}, }
@article {pmid25006989, year = {2014}, author = {Pallav, K and Dowd, SE and Villafuerte, J and Yang, X and Kabbani, T and Hansen, J and Dennis, M and Leffler, DA and Newburg, DS and Kelly, CP}, title = {Effects of polysaccharopeptide from Trametes versicolor and amoxicillin on the gut microbiome of healthy volunteers: a randomized clinical trial.}, journal = {Gut microbes}, volume = {5}, number = {4}, pages = {458-467}, doi = {10.4161/gmic.29558}, pmid = {25006989}, issn = {1949-0984}, support = {8UL1TR000170-05/TR/NCATS NIH HHS/United States ; }, mesh = {Adult ; Amoxicillin/*administration &amp; dosage ; Anti-Bacterial Agents/*administration &amp; dosage ; Feces/microbiology ; Female ; Gastrointestinal Tract/*microbiology ; Healthy Volunteers ; Humans ; Male ; Metagenomics ; Microbiota/*drug effects ; Middle Aged ; *Prebiotics ; Proteoglycans/*administration &amp; dosage/isolation &amp; purification ; Trametes/*chemistry ; Young Adult ; }, abstract = {BACKGROUND: Interactions between the microbial flora of the intestine and the human host play a critical role inmaintaining intestinal health and in the pathophysiology of a wide variety of disorders such as antibiotic associated diarrhea, Clostridium difficile infection, and inflammatory bowel disease. Prebiotics can confer health benefits by beneficial effects on the intestinal microbiome, whereas antibiotics can disrupt the microbiome leading to diarrhea andother side effects.<br><br>AIM: To compare the effects of the prebiotic, polysaccharopeptide from Trametes versicolor, to those of the antibiotic,amoxicillin, on the human gut microbiome<br><br>METHODS: Twenty-four healthy volunteers were randomized to receive PSP, amoxicillin, or no treatment (control).Stool specimens were analyzed using bTEFAP microbial ecology methods on seven occasions over 8 weeks from each participant in the active treatment groups and on three occasions for the controls.<br><br>RESULTS: Twenty-two of 24 participants completed the protocol. PSP led to clear and consistent microbiome changes consistent with its activity as a prebiotic. Despite the diversity of the human microbiome we noted strong microbiome clustering among subjects. Baseline microbiomes tended to remain stable and to overshadow the treatment effects.Amoxicillin treatment caused substantial microbiome changes most notably an increase in Escherichia/Shigella. Antibiotic associated changes persisted to the end of the study, 42 days after antibiotic therapy ended.<br><br>CONCLUSIONS: The microbiomes of healthy individuals show substantial diversity but remain stable over time.The antibiotic amoxicillin alters the microbiome and recovery from this disruption can take several weeks. PSP from T. versicolor acts as a prebiotic to modulate human intestinal microbiome composition.}, }
@article {pmid24997037, year = {2014}, author = {Karavolos, MH and Khan, CM}, title = {Multidirectional chemical signalling between Mammalian hosts, resident microbiota, and invasive pathogens: neuroendocrine hormone-induced changes in bacterial gene expression.}, journal = {Advances in experimental medicine and biology}, volume = {817}, number = {}, pages = {241-253}, doi = {10.1007/978-1-4939-0897-4_11}, pmid = {24997037}, issn = {0065-2598}, mesh = {Animals ; Bacteria/*genetics ; *Gene Expression Regulation, Bacterial ; Host-Pathogen Interactions/*physiology ; Humans ; Microbiota/*physiology ; Neurotransmitter Agents/*physiology ; Quorum Sensing ; Receptors, Adrenergic/physiology ; Signal Transduction/*physiology ; }, abstract = {Host-pathogen communication appears to be crucial in establishing the outcome of bacterial infections. There is increasing evidence to suggest that this communication can take place by bacterial pathogens sensing and subsequently responding to host neuroendocrine (NE) stress hormones. Bacterial pathogens have developed mechanisms allowing them to eavesdrop on these communication pathways within their hosts. These pathogens can use intercepted communication signals to adjust their fitness to persist and cause disease in their hosts. Recently, there have been numerous studies highlighting the ability of NE hormones to act as an environmental cue for pathogens, helping to steer their responses during host infection. Host NE hormone sensing can take place indirectly or directly via bacterial adrenergic receptors (BARs). The resulting changes in bacterial gene expression can be of strategic benefit to the pathogen. Furthermore, it is intriguing that not only can bacteria sense NE stress hormones but they are also able to produce key signalling molecules known as autoinducers. The rapid advances in our knowledge of the human microbiome, and its impact on health and disease highlights the potential importance of communication between the microbiota, pathogens and the host. It is indeed likely that the microbiota input significantly in the neuroendocrinological homeostasis of the host by catabolic, anabolic, and signalling processes. The arrival of unwanted guests, such as bacterial pathogens, clearly has a major impact on these delicately balanced interactions. Unravelling the pathways involved in interkingdom communication between invading bacterial pathogens, the resident microbiota, and hosts, may provide novel targets in our continuous search for new antimicrobials to control disease.}, }
@article {pmid25816640, year = {2014}, author = {Kungurtseva, EA and Popkova, SM and Leschenko, OY}, title = {[Reciprocal formation of mucosal microflora of open cavities of different habitats in women as an important factor of their reproductive health].}, journal = {Vestnik Rossiiskoi akademii meditsinskikh nauk}, volume = {}, number = {9-10}, pages = {27-32}, doi = {10.15690/vramn.v69i9-10.1128}, pmid = {25816640}, issn = {0869-6047}, mesh = {Adult ; Female ; Humans ; Intestinal Mucosa/microbiology ; Mucous Membrane/*microbiology ; Pregnancy ; *Reproductive Health ; Vagina/*microbiology ; Vaginosis, Bacterial/microbiology ; }, abstract = {This review presents the current data on the human microbiome. In recent increase of erased and primary chronic forms of inflammatory diseases of the female genital organs is observed, in which the clinical manifestations are varied, but the symptoms are not so much related with the changes in the pelvic organs, but with abnormalities in other body systems, secondarily involved in the pathological process. Recent research proved mutual influence of intestinal, vaginal and nasopharyngeal biocenosis. Women with vaginal microbiota disorders often revealed intestinal dysbiosis and chronic diseases of ENT (Ear Nose Throat) organs, which in turn contributes to chronic inflammatory process of pelvic organs, failure of therapeutic interventions, reduced quality of life and increased risk of adverse pregnancy outcomes.}, }
@article {pmid25755488, year = {2013}, author = {Bawa, M and Saraswat, VA}, title = {Gut-liver axis: role of inflammasomes.}, journal = {Journal of clinical and experimental hepatology}, volume = {3}, number = {2}, pages = {141-149}, pmid = {25755488}, issn = {0973-6883}, abstract = {Inflammasomes are large multiprotein complexes that have the ability to sense intracellular danger signals through special NOD-like receptors or NLRs. They include NLRP3, NLRC4, AIM2 and NLRP6. They are involved in recognizing diverse microbial (bacteria, viruses, fungi and parasites), stress and damage signals, which result in direct activation of caspase-1, leading to secretion of potent pro-inflammatory cytokines and pyroptosis. NLRP3 is the most studied antimicrobial immune response inflammasome. Recent studies reveal expression of inflammasomes in innate immune response cells including monocytes, macrophages, neutrophils, and dendritic cells. Inflammasome deficiency has been linked to alterations in the gastrointestinal microflora. Alterations in the microbiome population and/or changes in gut permeability promote microbial translocation into the portal circulation and thus directly to the liver. Gut derived lipopolysaccharides (LPS) play a significant role in several liver diseases. Recent advancements in the sequencing technologies along with improved methods in metagenomics and bioinformatics have provided effective tools for investigating the 10(14) microorganisms of the human microbiome that inhabit the human gut. In this review, we examine the significance of inflammasomes in relation to the gut microflora and liver. This review also highlights the emerging functions of human microbiota in health and liver diseases.}, }
@article {pmid25525499, year = {2013}, author = {Lewis, SS and Anderson, DJ}, title = {Treatment of Clostridium difficile infection: recent trial results.}, journal = {Clinical investigation}, volume = {3}, number = {9}, pages = {875-886}, pmid = {25525499}, issn = {2041-6792}, support = {K23 AI095357/AI/NIAID NIH HHS/United States ; }, abstract = {Clostridium difficile is a major cause of infection worldwide and is associated with increasing morbidity and mortality in vulnerable patient populations. Metronidazole and oral vancomycin are the currently recommended therapies for the treatment of C. difficile infection (CDI) but are associated with unacceptably high rates of disease recurrence. Novel therapies for the treatment of CDI and prevention of recurrent CDI are urgently needed. Important developments in the treatment of CDI are currently underway and include: novel antibacterial agents with narrower antimicrobial spectra of activity, manipulation of the gut microbiota and enhancement of the host antibody immune response.}, }
@article {pmid24997028, year = {2014}, author = {Fodor, A}, title = {Utilizing "omics" tools to study the complex gut ecosystem.}, journal = {Advances in experimental medicine and biology}, volume = {817}, number = {}, pages = {25-38}, doi = {10.1007/978-1-4939-0897-4_2}, pmid = {24997028}, issn = {0065-2598}, mesh = {Animals ; *Ecosystem ; Host-Pathogen Interactions/*physiology ; Humans ; Intestines/*microbiology ; Metagenome/*physiology ; Microbiota/*physiology ; RNA, Ribosomal, 16S/chemistry ; }, abstract = {In a healthy gut, the immune system tolerates a diverse microbial commensal community avoiding inappropriate inflammation responses and minimizing the presence of pathogens. When the balance between host and microbes is disrupted, risk for disease increases. There is mounting evidence that microbial dysbiosis is a substantial risk factor for common gut diseases including IBS, IBD and colorectal cancer. Understanding this dysbiosis is challenging because of the extraordinary complexity of the gut ecosystem and the tremendous variability between healthy individuals in the taxa that make up the human microbiome. Advances in technology, especially sequencing technology, are beginning to allow for a full description of this complexity. In this review, we consider how new "omics" technology can be applied to the study of the gut ecosystem in human and animal models with special consideration given to factors that should be considered in the design of experiments and clinical trials.}, }
@article {pmid24995004, year = {2014}, author = {Parfrey, LW and Walters, WA and Lauber, CL and Clemente, JC and Berg-Lyons, D and Teiling, C and Kodira, C and Mohiuddin, M and Brunelle, J and Driscoll, M and Fierer, N and Gilbert, JA and Knight, R}, title = {Communities of microbial eukaryotes in the mammalian gut within the context of environmental eukaryotic diversity.}, journal = {Frontiers in microbiology}, volume = {5}, number = {}, pages = {298}, pmid = {24995004}, issn = {1664-302X}, support = {R01 HG004872/HG/NHGRI NIH HHS/United States ; T32 GM008759/GM/NIGMS NIH HHS/United States ; T32 GM142607/GM/NIGMS NIH HHS/United States ; }, abstract = {Eukaryotic microbes (protists) residing in the vertebrate gut influence host health and disease, but their diversity and distribution in healthy hosts is poorly understood. Protists found in the gut are typically considered parasites, but many are commensal and some are beneficial. Further, the hygiene hypothesis predicts that association with our co-evolved microbial symbionts may be important to overall health. It is therefore imperative that we understand the normal diversity of our eukaryotic gut microbiota to test for such effects and avoid eliminating commensal organisms. We assembled a dataset of healthy individuals from two populations, one with traditional, agrarian lifestyles and a second with modern, westernized lifestyles, and characterized the human eukaryotic microbiota via high-throughput sequencing. To place the human gut microbiota within a broader context our dataset also includes gut samples from diverse mammals and samples from other aquatic and terrestrial environments. We curated the SILVA ribosomal database to reflect current knowledge of eukaryotic taxonomy and employ it as a phylogenetic framework to compare eukaryotic diversity across environment. We show that adults from the non-western population harbor a diverse community of protists, and diversity in the human gut is comparable to that in other mammals. However, the eukaryotic microbiota of the western population appears depauperate. The distribution of symbionts found in mammals reflects both host phylogeny and diet. Eukaryotic microbiota in the gut are less diverse and more patchily distributed than bacteria. More broadly, we show that eukaryotic communities in the gut are less diverse than in aquatic and terrestrial habitats, and few taxa are shared across habitat types, and diversity patterns of eukaryotes are correlated with those observed for bacteria. These results outline the distribution and diversity of microbial eukaryotic communities in the mammalian gut and across environments.}, }
@article {pmid24990702, year = {2014}, author = {Panchin, AY and Tuzhikov, AI and Panchin, YV}, title = {Midichlorians--the biomeme hypothesis: is there a microbial component to religious rituals?.}, journal = {Biology direct}, volume = {9}, number = {}, pages = {14}, pmid = {24990702}, issn = {1745-6150}, mesh = {Animals ; Bacteria/*metabolism ; *Ceremonial Behavior ; Humans ; *Models, Biological ; *Religion ; }, abstract = {BACKGROUND: Cutting edge research of human microbiome diversity has led to the development of the microbiome-gut-brain axis concept, based on the idea that gut microbes may have an impact on the behavior of their human hosts. Many examples of behavior-altering parasites are known to affect members of the animal kingdom. Some prominent examples include Ophiocordyceps unilateralis (fungi), Toxoplasma gondii (protista), Wolbachia (bacteria), Glyptapanteles sp. (arthropoda), Spinochordodes tellinii (nematomorpha) and Dicrocoelium dendriticum (flat worm). These organisms belong to a very diverse set of taxonomic groups suggesting that the phenomena of parasitic host control might be more common in nature than currently established and possibly overlooked in humans.<br><br>Some microorganisms would gain an evolutionary advantage by encouraging human hosts to perform certain rituals that favor microbial transmission. We hypothesize that certain aspects of religious behavior observed in the human society could be influenced by microbial host control and that the transmission of some religious rituals could be regarded as the simultaneous transmission of both ideas (memes) and parasitic organisms.<br><br>TESTING THE HYPOTHESIS: We predict that next-generation microbiome sequencing of samples obtained from gut or brain tissues of control subjects and subjects with a history of voluntary active participation in certain religious rituals that promote microbial transmission will lead to the discovery of microbes, whose presence has a consistent and positive association with religious behavior. Our hypothesis also predicts a decline of participation in religious rituals in societies with improved sanitation.<br><br>If proven true, our hypothesis may provide insights on the origin and pervasiveness of certain religious practices and provide an alternative explanation for recently published positive associations between parasite-stress and religiosity. The discovery of novel microorganisms that affect host behavior may improve our understanding of neurobiology and neurochemistry, while the diversity of such organisms may be of interest to evolutionary biologists and religious scholars.<br><br>REVIEWERS: This article was reviewed by Prof. Dan Graur, Dr. Rob Knight and Dr. Eugene Koonin.}, }
@article {pmid24976806, year = {2014}, author = {Aroniadis, OC and Brandt, LJ}, title = {Intestinal microbiota and the efficacy of fecal microbiota transplantation in gastrointestinal disease.}, journal = {Gastroenterology &amp; hepatology}, volume = {10}, number = {4}, pages = {230-237}, pmid = {24976806}, issn = {1554-7914}, support = {UL1 TR001073/TR/NCATS NIH HHS/United States ; }, abstract = {Fecal microbiota transplantation (FMT) refers to the infusion of a fecal suspension from a healthy person into the gastrointestinal (GI) tract of another person to cure a specific disease. FMT is by no means a new therapeutic modality, although it was only relatively recently that stool was shown to be a biologically active, complex mixture of living organisms with great therapeutic potential for recurrent Clostridium difficile infection and perhaps other GI and non-GI disorders. The published revelations about the human microbiome are bringing the strength of science to clinical observation and enhancing the understanding of not only disease but also how much of a person's daily function and health depends on the microorganisms living in intimate relationship with each cell in the body.}, }
@article {pmid24965364, year = {2014}, author = {Ma, L and Kim, J and Hatzenpichler, R and Karymov, MA and Hubert, N and Hanan, IM and Chang, EB and Ismagilov, RF}, title = {Gene-targeted microfluidic cultivation validated by isolation of a gut bacterium listed in Human Microbiome Project's Most Wanted taxa.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {111}, number = {27}, pages = {9768-9773}, pmid = {24965364}, issn = {1091-6490}, support = {UL1 TR000430/TR/NCATS NIH HHS/United States ; R01HG005826/HG/NHGRI NIH HHS/United States ; R01 HG005826/HG/NHGRI NIH HHS/United States ; R37 DK047722/DK/NIDDK NIH HHS/United States ; R01 DK047722/DK/NIDDK NIH HHS/United States ; }, mesh = {*Gene Targeting ; Humans ; Intestines/*microbiology ; *Microbiota ; *Microfluidic Analytical Techniques ; Molecular Sequence Data ; }, abstract = {This paper describes a microfluidics-based workflow for genetically targeted isolation and cultivation of microorganisms from complex clinical samples. Data sets from high-throughput sequencing suggest the existence of previously unidentified bacterial taxa and functional genes with high biomedical importance. Obtaining isolates of these targets, preferably in pure cultures, is crucial for advancing understanding of microbial genetics and physiology and enabling physical access to microbes for further applications. However, the majority of microbes have not been cultured, due in part to the difficulties of both identifying proper growth conditions and characterizing and isolating each species. We describe a method that enables genetically targeted cultivation of microorganisms through a combination of microfluidics and on- and off-chip assays. This method involves (i) identification of cultivation conditions for microbes using growth substrates available only in small quantities as well as the correction of sampling bias using a "chip wash" technique; and (ii) performing on-chip genetic assays while also preserving live bacterial cells for subsequent scale-up cultivation of desired microbes, by applying recently developed technology to create arrays of individually addressable replica microbial cultures. We validated this targeted approach by cultivating a bacterium, here referred to as isolate microfluidicus 1, from a human cecal biopsy. Isolate microfluidicus 1 is, to our knowledge, the first successful example of targeted cultivation of a microorganism from the high-priority group of the Human Microbiome Project's "Most Wanted" list, and, to our knowledge, the first cultured representative of a previously unidentified genus of the Ruminococcaceae family.}, }
@article {pmid24965363, year = {2014}, author = {Eren, AM and Borisy, GG and Huse, SM and Mark Welch, JL}, title = {Oligotyping analysis of the human oral microbiome.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {111}, number = {28}, pages = {E2875-84}, pmid = {24965363}, issn = {1091-6490}, support = {DE022586/DE/NIDCR NIH HHS/United States ; UH3 DK083993/DK/NIDDK NIH HHS/United States ; DK083993/DK/NIDDK NIH HHS/United States ; UH2 DK083993/DK/NIDDK NIH HHS/United States ; R01 DE022586/DE/NIDCR NIH HHS/United States ; }, mesh = {Adolescent ; Adult ; *Bacteria/classification/genetics ; *Databases, Nucleic Acid ; Female ; *Genes, Bacterial ; *Genes, rRNA ; Humans ; Male ; Microbiota ; Mouth Mucosa/*microbiology ; RNA, Bacterial/*genetics ; RNA, Ribosomal, 16S/*genetics ; }, abstract = {The Human Microbiome Project provided a census of bacterial populations in healthy individuals, but an understanding of the biomedical significance of this census has been hindered by limited taxonomic resolution. A high-resolution method termed oligotyping overcomes this limitation by evaluating individual nucleotide positions using Shannon entropy to identify the most information-rich nucleotide positions, which then define oligotypes. We have applied this method to comprehensively analyze the oral microbiome. Using Human Microbiome Project 16S rRNA gene sequence data for the nine sites in the oral cavity, we identified 493 oligotypes from the V1-V3 data and 360 oligotypes from the V3-V5 data. We associated these oligotypes with species-level taxon names by comparison with the Human Oral Microbiome Database. We discovered closely related oligotypes, differing sometimes by as little as a single nucleotide, that showed dramatically different distributions among oral sites and among individuals. We also detected potentially pathogenic taxa in high abundance in individual samples. Numerous oligotypes were preferentially located in plaque, others in keratinized gingiva or buccal mucosa, and some oligotypes were characteristic of habitat groupings such as throat, tonsils, tongue dorsum, hard palate, and saliva. The differing habitat distributions of closely related oligotypes suggest a level of ecological and functional biodiversity not previously recognized. We conclude that the Shannon entropy approach of oligotyping has the capacity to analyze entire microbiomes, discriminate between closely related but distinct taxa and, in combination with habitat analysis, provide deep insight into the microbial communities in health and disease.}, }
@article {pmid24958850, year = {2014}, author = {Campion, SL and Brodie, TM and Fischer, W and Korber, BT and Rossetti, A and Goonetilleke, N and McMichael, AJ and Sallusto, F}, title = {Proteome-wide analysis of HIV-specific naive and memory CD4(+) T cells in unexposed blood donors.}, journal = {The Journal of experimental medicine}, volume = {211}, number = {7}, pages = {1273-1280}, pmid = {24958850}, issn = {1540-9538}, support = {UM1 AI100645/AI/NIAID NIH HHS/United States ; MR/K012037/1/MRC_/Medical Research Council/United Kingdom ; HHSN272201300006C/AI/NIAID NIH HHS/United States ; P30 AI027763/AI/NIAID NIH HHS/United States ; UM1-AI100645-01/AI/NIAID NIH HHS/United States ; }, mesh = {AIDS Vaccines/immunology ; Antigens, Viral/*immunology ; CD4-Positive T-Lymphocytes ; Cross Reactions ; Epitopes, T-Lymphocyte/*immunology ; Female ; HIV-1/*immunology ; Humans ; *Immunologic Memory ; Male ; Microbiota/*immunology ; Peptides/*immunology ; Proteome/*immunology ; Viral Proteins/*immunology ; }, abstract = {The preexisting HIV-1-specific T cell repertoire must influence both the immunodominance of T cells after infection and immunogenicity of vaccines. We directly compared two methods for measuring the preexisting CD4(+) T cell repertoire in healthy HIV-1-negative volunteers, the HLA-peptide tetramer enrichment and T cell library technique, and show high concordance (r = 0.989). Using the library technique, we examined whether naive, central memory, and/or effector memory CD4(+) T cells specific for overlapping peptides spanning the entire HIV-1 proteome were detectable in 10 HLA diverse, HIV-1-unexposed, seronegative donors. HIV-1-specific cells were detected in all donors at a mean of 55 cells/million naive cells and 38.9 and 34.1 cells/million in central and effector memory subsets. Remarkably, peptide mapping showed most epitopes recognized by naive (88%) and memory (56%) CD4(+) T cells had been previously reported in natural HIV-1 infection. Furthermore, 83% of epitopes identified in preexisting memory subsets shared epitope length matches (8-12 amino acids) with human microbiome proteins, suggestive of a possible cross-reactive mechanism. These results underline the power of a proteome-wide analysis of peptide recognition by human T cells for the identification of dominant antigens and provide a baseline for optimizing HIV-1-specific helper cell responses by vaccination.}, }
@article {pmid24957091, year = {2014}, author = {Barzegari, A and Saeedi, N and Saei, AA}, title = {Shrinkage of the human core microbiome and a proposal for launching microbiome biobanks.}, journal = {Future microbiology}, volume = {9}, number = {5}, pages = {639-656}, doi = {10.2217/fmb.14.22}, pmid = {24957091}, issn = {1746-0921}, mesh = {Animals ; Anti-Bacterial Agents/pharmacology ; *Biodiversity ; *Biological Specimen Banks ; Diet ; Gastrointestinal Tract/*microbiology ; Humans ; Metabolic Syndrome/immunology ; Mice ; *Microbiota ; Obesity/immunology ; Probiotics/therapeutic use ; }, abstract = {The Human Microbiome Project (HMP) revealed the significance of the gut microbiome in promoting health. Disruptions in microbiome composition are associated with the pathogenesis of numerous diseases. The indigenous microflora has co-evolved with humans for millions of years and humans have preserved the inherited microbiomes through consumption of fermented foods and interactions with environmental microbes. Through modernization, traditional foods were abandoned, native food starters were substituted with industrial products, vaccines and antibiotics were used, extreme hygiene measures were taken, the rate of cesarean section increased, and breast feeding changed into formula. These factors have reduced human exposure to microbial symbionts and led to shrinkage of the core microbiome. Reduction in microbiome biodiversity can compromise the human immune system and predispose individuals to several modern diseases. This article suggests launching microbiome biobanks for archiving native microbiomes, supervising antibiotic use, probiotic design and native starter production, as well as advertising a revisit to native lifestyles.}, }
@article {pmid24953716, year = {2014}, author = {Actis, GC}, title = {The gut microbiome.}, journal = {Inflammation &amp; allergy drug targets}, volume = {13}, number = {4}, pages = {217-223}, doi = {10.2174/1871528113666140623113221}, pmid = {24953716}, issn = {2212-4055}, mesh = {Animals ; Diet ; Escherichia coli/drug effects/growth &amp; development ; Gastrointestinal Tract/drug effects/*microbiology ; Humans ; Inflammation/drug therapy/microbiology ; Intestinal Mucosa/microbiology ; Microbiota/*physiology ; Obesity/microbiology ; Probiotics/pharmacology ; }, abstract = {Since the discovery and use of the microscope in the 17(th) century, we know that we host trillions of micro-organisms mostly in the form of bacteria indwelling the "barrier organs" skin, gut, and airways. They exert regulatory functions, are in a continuous dialogue with the intestinal epithelia, influence energy handling, produce nutrients, and may cause diabetes and obesity. The human microbiome has developed by modulating or avoiding inflammatory responses; the host senses bacterial presence through cell surface sensors (the Toll-like receptors) as well as by refining mucous barriers as passive defense mechanisms. The cell density and composition of the microbiome are variable and multifactored. The way of delivery establishes the type of initial flora; use of antibiotics is another factor; diet composition after weaning will shape the adult's microbiome composition, depending on the subject's life-style. Short-chain fatty acids participate in the favoring action exerted by microbiome in the pathogenesis of type-2 diabetes and obesity. Clinical observation has pinpointed a sharp rise of various dysimmune conditions in the last decades, including IBD and rheumatoid arthritis, changes that outweigh the input of simple heritability. It is nowadays proposed that the microbiome, incapable to keep up with the changes of our life-style and feeding sources in the past few decades might have contributed to these immune imbalances, finding itself inadequate to handle the changed gut environment. Another pathway to pathology is the rise of directly pathogenic phyla within a given microbiome: growth of adherent E. coli, of C. concisus, and of C. jejuni, might be examples of causes of local enteropathy, whereas the genus Prevotella copri is now suspected to be linked to rise of arthritic disorders. Inflammasomes are required to shape a non colitogenic flora. Treatment of IBD and infectious enteritides by the use of fecal transplant is warranted by this knowledge.}, }
@article {pmid24951561, year = {2014}, author = {Spinler, JK and Sontakke, A and Hollister, EB and Venable, SF and Oh, PL and Balderas, MA and Saulnier, DM and Mistretta, TA and Devaraj, S and Walter, J and Versalovic, J and Highlander, SK}, title = {From prediction to function using evolutionary genomics: human-specific ecotypes of Lactobacillus reuteri have diverse probiotic functions.}, journal = {Genome biology and evolution}, volume = {6}, number = {7}, pages = {1772-1789}, pmid = {24951561}, issn = {1759-6653}, support = {U01CA170930/CA/NCI NIH HHS/United States ; UH3 DK083990/DK/NIDDK NIH HHS/United States ; U54 HG003273/HG/NHGRI NIH HHS/United States ; R01 DK065075/DK/NIDDK NIH HHS/United States ; P30 DK056338/DK/NIDDK NIH HHS/United States ; R01 AT004326/AT/NCCIH NIH HHS/United States ; U01 CA170930/CA/NCI NIH HHS/United States ; U54 HG004973/HG/NHGRI NIH HHS/United States ; P30 DK56338/DK/NIDDK NIH HHS/United States ; UH3DK083990/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Cell Line ; *Evolution, Molecular ; *Genomics ; Humans ; Limosilactobacillus reuteri/genetics/*physiology ; Microarray Analysis ; Phylogeny ; *Probiotics ; }, abstract = {The vertebrate gut symbiont Lactobacillus reuteri has diversified into separate clades reflecting host origin. Strains show evidence of host adaptation, but how host-microbe coevolution influences microbial-derived effects on hosts is poorly understood. Emphasizing human-derived strains of L. reuteri, we combined comparative genomic analyses with functional assays to examine variations in host interaction among genetically distinct ecotypes. Within clade II or VI, the genomes of human-derived L. reuteri strains are highly conserved in gene content and at the nucleotide level. Nevertheless, they share only 70-90% of total gene content, indicating differences in functional capacity. Human-associated lineages are distinguished by genes related to bacteriophages, vitamin biosynthesis, antimicrobial production, and immunomodulation. Differential production of reuterin, histamine, and folate by 23 clade II and VI strains was demonstrated. These strains also differed with respect to their ability to modulate human cytokine production (tumor necrosis factor, monocyte chemoattractant protein-1, interleukin [IL]-1β, IL-5, IL-7, IL-12, and IL-13) by myeloid cells. Microarray analysis of representative clade II and clade VI strains revealed global regulation of genes within the reuterin, vitamin B12, folate, and arginine catabolism gene clusters by the AraC family transcriptional regulator, PocR. Thus, human-derived L. reuteri clade II and VI strains are genetically distinct and their differences affect their functional repertoires and probiotic features. These findings highlight the biological impact of microbe:host coevolution and illustrate the functional significance of subspecies differences in the human microbiome. Consideration of host origin and functional differences at the subspecies level may have major impacts on probiotic strain selection and considerations of microbial ecology in mammalian species.}, }
@article {pmid24950204, year = {2014}, author = {Huttenhower, C and Kostic, AD and Xavier, RJ}, title = {Inflammatory bowel disease as a model for translating the microbiome.}, journal = {Immunity}, volume = {40}, number = {6}, pages = {843-854}, pmid = {24950204}, issn = {1097-4180}, support = {P30 DK043351/DK/NIDDK NIH HHS/United States ; R01 DK092405/DK/NIDDK NIH HHS/United States ; U54 DE023798/DE/NIDCR NIH HHS/United States ; U54 DK102557/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Colitis, Ulcerative/*immunology/*microbiology ; Crohn Disease/*immunology/*microbiology ; *Disease Models, Animal ; Gastrointestinal Tract/immunology/microbiology ; Humans ; Metagenome ; Mice ; Microbiota/*immunology ; *Translational Research, Biomedical ; }, abstract = {The inflammatory bowel diseases (IBDs) are among the most closely studied chronic inflammatory disorders that involve environmental, host genetic, and commensal microbial factors. This combination of features has made IBD both an appropriate and a high-priority platform for translatable research in host-microbiome interactions. Decades of epidemiology have identified environmental risk factors, although most mechanisms of action remain unexplained. The genetic architecture of IBD has been carefully dissected in multiple large populations, identifying several responsible host epithelial and immune pathways but without yet a complete systems-level explanation. Most recently, the commensal gut microbiota have been found to be both ecologically and functionally perturbed during the disease, but with as-yet-unexplained heterogeneity among IBD subtypes and individual patients. IBD thus represents perhaps the most comprehensive current model for understanding the human microbiome's role in complex inflammatory disease. Here, we review the influences of the microbiota on IBD and its potential for translational medicine.}, }
@article {pmid24950202, year = {2014}, author = {Dorrestein, PC and Mazmanian, SK and Knight, R}, title = {Finding the missing links among metabolites, microbes, and the host.}, journal = {Immunity}, volume = {40}, number = {6}, pages = {824-832}, pmid = {24950202}, issn = {1097-4180}, support = {P01 DK078669/DK/NIDDK NIH HHS/United States ; R01 MH100556/MH/NIMH NIH HHS/United States ; U01 HG004866/HG/NHGRI NIH HHS/United States ; R01 HG004872/HG/NHGRI NIH HHS/United States ; R01 NS085910/NS/NINDS NIH HHS/United States ; /HHMI_/Howard Hughes Medical Institute/United States ; R01 DK078938/DK/NIDDK NIH HHS/United States ; }, mesh = {Bacterial Proteins/immunology ; Gastrointestinal Tract/immunology/microbiology ; Humans ; *Metabolome ; *Metagenome ; Microbiota/*genetics/*immunology ; }, abstract = {The unexpected diversity of the human microbiome and metabolome far exceeds the complexity of the human genome. Although we now understand microbial taxonomic and genetic repertoires in some populations, we are just beginning to assemble the necessary computational and experimental tools to understand the metabolome in comparable detail. However, even with the limited current state of knowledge, individual connections between microbes and metabolites, between microbes and immune function, and between metabolites and immune function are being established. Here, we provide our perspective on these connections and outline a systematic research program that could turn these individual links into a broader network that allows us to understand how these components interact. This program will enable us to exploit connections among the microbiome, metabolome, and host immune system to maintain health and perhaps help us understand how to reverse the processes that lead to a wide range of immune and other diseases.}, }
@article {pmid24949196, year = {2014}, author = {Wesolowska-Andersen, A and Bahl, MI and Carvalho, V and Kristiansen, K and Sicheritz-Pontén, T and Gupta, R and Licht, TR}, title = {Choice of bacterial DNA extraction method from fecal material influences community structure as evaluated by metagenomic analysis.}, journal = {Microbiome}, volume = {2}, number = {}, pages = {19}, pmid = {24949196}, issn = {2049-2618}, abstract = {BACKGROUND: In recent years, studies on the human intestinal microbiota have attracted tremendous attention. Application of next generation sequencing for mapping of bacterial phylogeny and function has opened new doors to this field of research. However, little attention has been given to the effects of choice of methodology on the output resulting from such studies.<br><br>RESULTS: IN THIS STUDY WE CONDUCTED A SYSTEMATIC COMPARISON OF THE DNA EXTRACTION METHODS USED BY THE TWO MAJOR COLLABORATIVE EFFORTS: The European MetaHIT and the American Human Microbiome Project (HMP). Additionally, effects of homogenizing the samples before extraction were addressed. We observed significant differences in distribution of bacterial taxa depending on the method. While eukaryotic DNA was most efficiently extracted by the MetaHIT protocol, DNA from bacteria within the Bacteroidetes phylum was most efficiently extracted by the HMP protocol.<br><br>CONCLUSIONS: Whereas it is comforting that the inter-individual variation clearly exceeded the variation resulting from choice of extraction method, our data highlight the challenge of comparing data across studies applying different methodologies.}, }
@article {pmid24925896, year = {2014}, author = {Vande Voorde, J and Balzarini, J and Liekens, S}, title = {An emerging understanding of the Janus face of the human microbiome: enhancement versus impairment of cancer therapy.}, journal = {The Journal of antimicrobial chemotherapy}, volume = {69}, number = {10}, pages = {2878-2880}, doi = {10.1093/jac/dku201}, pmid = {24925896}, issn = {1460-2091}, mesh = {Animals ; Humans ; *Metagenome ; *Microbiota ; Neoplasms/etiology/pathology/therapy ; }, }
@article {pmid24910773, year = {2014}, author = {Fernandes, AD and Reid, JN and Macklaim, JM and McMurrough, TA and Edgell, DR and Gloor, GB}, title = {Unifying the analysis of high-throughput sequencing datasets: characterizing RNA-seq, 16S rRNA gene sequencing and selective growth experiments by compositional data analysis.}, journal = {Microbiome}, volume = {2}, number = {}, pages = {15}, pmid = {24910773}, issn = {2049-2618}, abstract = {BACKGROUND: Experimental designs that take advantage of high-throughput sequencing to generate datasets include RNA sequencing (RNA-seq), chromatin immunoprecipitation sequencing (ChIP-seq), sequencing of 16S rRNA gene fragments, metagenomic analysis and selective growth experiments. In each case the underlying data are similar and are composed of counts of sequencing reads mapped to a large number of features in each sample. Despite this underlying similarity, the data analysis methods used for these experimental designs are all different, and do not translate across experiments. Alternative methods have been developed in the physical and geological sciences that treat similar data as compositions. Compositional data analysis methods transform the data to relative abundances with the result that the analyses are more robust and reproducible.<br><br>RESULTS: Data from an in vitro selective growth experiment, an RNA-seq experiment and the Human Microbiome Project 16S rRNA gene abundance dataset were examined by ALDEx2, a compositional data analysis tool that uses Bayesian methods to infer technical and statistical error. The ALDEx2 approach is shown to be suitable for all three types of data: it correctly identifies both the direction and differential abundance of features in the differential growth experiment, it identifies a substantially similar set of differentially expressed genes in the RNA-seq dataset as the leading tools and it identifies as differential the taxa that distinguish the tongue dorsum and buccal mucosa in the Human Microbiome Project dataset. The design of ALDEx2 reduces the number of false positive identifications that result from datasets composed of many features in few samples.<br><br>CONCLUSION: Statistical analysis of high-throughput sequencing datasets composed of per feature counts showed that the ALDEx2 R package is a simple and robust tool, which can be applied to RNA-seq, 16S rRNA gene sequencing and differential growth datasets, and by extension to other techniques that use a similar approach.}, }
@article {pmid24891987, year = {2014}, author = {Plotnikoff, GA and Riley, D}, title = {The human microbiome.}, journal = {Global advances in health and medicine}, volume = {3}, number = {3}, pages = {4-5}, pmid = {24891987}, issn = {2164-957X}, }
@article {pmid24888348, year = {2014}, author = {Fleischman, NM and Das, D and Kumar, A and Xu, Q and Chiu, HJ and Jaroszewski, L and Knuth, MW and Klock, HE and Miller, MD and Elsliger, MA and Godzik, A and Lesley, SA and Deacon, AM and Wilson, IA and Toney, MD}, title = {Molecular characterization of novel pyridoxal-5'-phosphate-dependent enzymes from the human microbiome.}, journal = {Protein science : a publication of the Protein Society}, volume = {23}, number = {8}, pages = {1060-1076}, pmid = {24888348}, issn = {1469-896X}, support = {P41 GM103393/GM/NIGMS NIH HHS/United States ; U54 GM094586/GM/NIGMS NIH HHS/United States ; 3R01GM054779-13S1/GM/NIGMS NIH HHS/United States ; }, mesh = {Crystallography, X-Ray ; Eubacterium/*enzymology ; Humans ; *Microbiota ; Models, Molecular ; Oxidoreductases/chemistry/*metabolism ; Porphyromonas gingivalis/*enzymology ; Protein Conformation ; Pyridoxal Phosphate/chemistry/*metabolism ; Transaminases/chemistry/*metabolism ; }, abstract = {Pyridoxal-5'-phosphate or PLP, the active form of vitamin B6, is a highly versatile cofactor that participates in a large number of mechanistically diverse enzymatic reactions in basic metabolism. PLP-dependent enzymes account for ∼1.5% of most prokaryotic genomes and are estimated to be involved in ∼4% of all catalytic reactions, making this an important class of enzymes. Here, we structurally and functionally characterize three novel PLP-dependent enzymes from bacteria in the human microbiome: two are from Eubacterium rectale, a dominant, nonpathogenic, fecal, Gram-positive bacteria, and the third is from Porphyromonas gingivalis, which plays a major role in human periodontal disease. All adopt the Type I PLP-dependent enzyme fold and structure-guided biochemical analysis enabled functional assignments as tryptophan, aromatic, and probable phosphoserine aminotransferases.}, }
@article {pmid24887286, year = {2014}, author = {Zhou, Y and Mihindukulasuriya, KA and Gao, H and La Rosa, PS and Wylie, KM and Martin, JC and Kota, K and Shannon, WD and Mitreva, M and Sodergren, E and Weinstock, GM}, title = {Exploration of bacterial community classes in major human habitats.}, journal = {Genome biology}, volume = {15}, number = {5}, pages = {R66}, pmid = {24887286}, issn = {1474-760X}, support = {U54HG004968/HG/NHGRI NIH HHS/United States ; }, mesh = {Bacteria/*classification/genetics/*isolation &amp; purification ; Demography ; Feces/microbiology ; Female ; Humans ; *Microbiota ; Mouth/microbiology ; Nose/microbiology ; Skin/microbiology ; Vagina/microbiology ; }, abstract = {BACKGROUND: Determining bacterial abundance variation is the first step in understanding bacterial similarity between individuals. Categorization of bacterial communities into groups or community classes is the subsequent step in describing microbial distribution based on abundance patterns. Here, we present an analysis of the groupings of bacterial communities in stool, nasal, skin, vaginal and oral habitats in a healthy cohort of 236 subjects from the Human Microbiome Project.<br><br>RESULTS: We identify distinct community group patterns in the anterior nares, four skin sites, and vagina at the genus level. We also confirm three enterotypes previously identified in stools. We identify two clusters with low silhouette values in most oral sites, in which bacterial communities are more homogeneous. Subjects sharing a community class in one habitat do not necessarily share a community class in another, except in the three vaginal sites and the symmetric habitats of the left and right retroauricular creases. Demographic factors, including gender, age, and ethnicity, significantly influence community composition in several habitats. Community classes in the vagina, retroauricular crease and stool are stable over approximately 200 days.<br><br>CONCLUSION: The community composition, association of demographic factors with community classes, and demonstration of community stability deepen our understanding of the variability and dynamics of human microbiomes. This also has significant implications for experimental designs that seek microbial correlations with clinical phenotypes.}, }
@article {pmid24882755, year = {2014}, author = {Cénit, MC and Matzaraki, V and Tigchelaar, EF and Zhernakova, A}, title = {Rapidly expanding knowledge on the role of the gut microbiome in health and disease.}, journal = {Biochimica et biophysica acta}, volume = {1842}, number = {10}, pages = {1981-1992}, doi = {10.1016/j.bbadis.2014.05.023}, pmid = {24882755}, issn = {0006-3002}, abstract = {The human gut is colonized by a wide diversity of micro-organisms, which are now known to play a key role in the human host by regulating metabolic functions and immune homeostasis. Many studies have indicated that the genomes of our gut microbiota, known as the gut microbiome or our "other genome" could play an important role in immune-related, complex diseases, and growing evidence supports a causal role for gut microbiota in regulating predisposition to diseases. A comprehensive analysis of the human gut microbiome is thus important to unravel the exact mechanisms by which the gut microbiota are involved in health and disease. Recent advances in next-generation sequencing technology, along with the development of metagenomics and bioinformatics tools, have provided opportunities to characterize the microbial communities. Furthermore, studies using germ-free animals have shed light on how the gut microbiota are involved in autoimmunity. In this review we describe the different approaches used to characterize the human microbiome, review current knowledge about the gut microbiome, and discuss the role of gut microbiota in immune homeostasis and autoimmunity. Finally, we indicate how this knowledge could be used to improve human health by manipulating the gut microbiota. This article is part of a Special Issue entitled: From Genome to Function.}, }
@article {pmid24882717, year = {2014}, author = {Proal, AD and Albert, PJ and Marshall, TG}, title = {Inflammatory disease and the human microbiome.}, journal = {Discovery medicine}, volume = {17}, number = {95}, pages = {257-265}, pmid = {24882717}, issn = {1944-7930}, mesh = {Gene Expression Regulation, Bacterial ; Genome, Human ; Genomics ; Humans ; Immunity, Innate ; Inflammation/*microbiology/*physiopathology ; Metagenome ; *Microbiota ; }, abstract = {The human body is a superorganism in which thousands of microbial genomes continually interact with the human genome. A range of physical and neurological inflammatory diseases are now associated with shifts in microbiome composition. Seemingly disparate inflammatory conditions may arise from similar disruption of microbiome homeostasis. Intracellular pathogens long associated with inflammatory disease are able to slow the innate immune response by dysregulating activity of the VDR nuclear receptor. This facilitates the ability of other species to gradually accumulate in tissue and blood, where they generate proteins and metabolites that significantly interfere with the body's metabolic processes. The microbes that contribute to this dysfunction are often inherited from family members. Immunosuppressive therapies for inflammatory disease allow pathogens driving these processes to spread with greater ease. In contrast to immunosuppression, treatments that stimulate the immune system seem to allow for reversal of this pathogen-induced genomic dysregulation.}, }
@article {pmid24872820, year = {2014}, author = {Kramer, MF and Heath, MD}, title = {Probiotics in the treatment of chronic rhinoconjunctivitis and chronic rhinosinusitis.}, journal = {Journal of allergy}, volume = {2014}, number = {}, pages = {983635}, pmid = {24872820}, issn = {1687-9783}, abstract = {Chronic rhinitis and rhinosinusitis (CRS) are relevant health conditions affecting significant percentages of the western population. They are frequently coexisting and aggravating diseases. Both are chronic, noninfectious, and inflammatory conditions sharing to a certain extent important pathophysiologic similarities. Beneficial effects of probiotics are long known to mankind. Research is beginning to unravel the true nature of the human microbiome and its interaction with the immune system. The growing prevalence of atopic diseases in the developed world led to the proposition of the "hygiene hypothesis." Dysbiosis is linked to atopic diseases; probiotic supplementation is able to alter the microbiome and certain probiotic strains have immunomodulatory effects in favour of a suppression of Th-2 and stimulation of a Th1 profile. This review focuses on randomized, double-blind, placebo-controlled trials investigating clinical parameters in the treatment of chronic rhinitis and CRS. An emerging number of publications demonstrate beneficial effects using probiotics in clinical double-blind placebo-controlled (dbpc) trials in allergic rhinitis (AR). Using probiotics as complementary treatment options in AR seems to be a promising concept although the evidence is of a preliminary nature to date and more convincing trials are needed. There are no current data to support the use of probiotics in non-AR or CRS.}, }
@article {pmid24872344, year = {2014}, author = {Viertel, TM and Ritter, K and Horz, HP}, title = {Viruses versus bacteria-novel approaches to phage therapy as a tool against multidrug-resistant pathogens.}, journal = {The Journal of antimicrobial chemotherapy}, volume = {69}, number = {9}, pages = {2326-2336}, doi = {10.1093/jac/dku173}, pmid = {24872344}, issn = {1460-2091}, mesh = {Animals ; Bacteria/*drug effects/*virology ; Bacterial Infections/*microbiology/*therapy ; Bacteriophages/*growth &amp; development ; Biological Therapy/*methods ; Clinical Trials as Topic ; Disease Models, Animal ; Drug Discovery/trends ; *Drug Resistance, Multiple, Bacterial ; Humans ; Treatment Outcome ; }, abstract = {Bacteriophage therapy (the application of phages to treat bacterial infections) has a tradition dating back almost a century, but interest in phage therapy slowed down in the West when antibiotics were discovered. With the emerging threat of infections caused by multidrug-resistant bacteria and scarce prospects of newly introduced antibiotics in the future, phages are currently being reconsidered as alternative therapeutics. Conventional phage therapy uses lytic bacteriophages for treatment and recent human clinical trials have revealed encouraging results. In addition, several other modern approaches to phages as therapeutics have been made in vitro and in animal models. Dual therapy with phages and antibiotics has resulted in significant reductions in the number of bacterial pathogens. Bioengineered phages have overcome many of the problems of conventional phage therapy, enabled targeted drug delivery or reversed the resistance of drug-resistant bacteria. The use of enzymes derived from phages, such as endolysin, as therapeutic agents has been efficient in the elimination of Gram-positive pathogens. This review presents novel strategies for phage-related therapies and describes our current knowledge of natural bacteriophages within the human microbiome. Our aim is to provide an overview of the high number of different methodological concepts, thereby encouraging further research on this topic, with the ultimate goal of using phages as therapeutic or preventative medicines in daily clinical practice.}, }
@article {pmid24864144, year = {2014}, author = {Cho, T and Nagao, J and Imayoshi, R and Tanaka, Y}, title = {Importance of Diversity in the Oral Microbiota including Candida Species Revealed by High-Throughput Technologies.}, journal = {International journal of dentistry}, volume = {2014}, number = {}, pages = {454391}, pmid = {24864144}, issn = {1687-8728}, abstract = {Taking advantage of high-throughput technologies, deep sequencing of the human microbiome has revealed commensal bacteria independent of the ability to culture them. The composition of the commensal microbiome is dependent on bacterial diversity and the state of the host regulated by the immune system. Candida species are well known as components of the commensal oral microbiota. Candida species frequently colonize and develop biofilms on medical devices like dentures and catheters. Therefore, Candida biofilm on dentures leads to a decrease in the bacterial diversity and then to a change in the composition of the oral microbiota. A disturbance in the balance between commensal bacteria and the host immune system results in a switch from a healthy state to a diseased state even in the limited oral niche.}, }
@article {pmid24855008, year = {2014}, author = {Michaud, DS and Izard, J}, title = {Microbiota, oral microbiome, and pancreatic cancer.}, journal = {Cancer journal (Sudbury, Mass.)}, volume = {20}, number = {3}, pages = {203-206}, pmid = {24855008}, issn = {1540-336X}, support = {R01 CA166150/CA/NCI NIH HHS/United States ; U24 DK097153/DK/NIDDK NIH HHS/United States ; DK097153/DK/NIDDK NIH HHS/United States ; CA166150/CA/NCI NIH HHS/United States ; }, mesh = {Humans ; Inflammation/immunology/microbiology/pathology ; *Microbiota ; Mouth/*microbiology ; Pancreatic Neoplasms/immunology/*microbiology/pathology ; Risk Factors ; }, abstract = {Only 30% of patients with a diagnosis of pancreatic cancer survive 1 year after the diagnosis. Progress in understanding the causes of pancreatic cancer has been made, including solidifying the associations with obesity and diabetes, and a proportion of cases should be preventable through lifestyle modifications. Unfortunately, identifying reliable biomarkers of early pancreatic cancer has been extremely challenging, and no effective screening modality is currently available for this devastating form of cancer. Recent data suggest that the microbiota may play a role in the disease process, but many questions remain. Future studies focusing on the human microbiome, both etiologically and as a marker of disease susceptibility, should shed light on how to better tackle prevention, early detection, and treatment of this highly fatal disease.}, }
@article {pmid24855007, year = {2014}, author = {Zambirinis, CP and Pushalkar, S and Saxena, D and Miller, G}, title = {Pancreatic cancer, inflammation, and microbiome.}, journal = {Cancer journal (Sudbury, Mass.)}, volume = {20}, number = {3}, pages = {195-202}, pmid = {24855007}, issn = {1540-336X}, support = {R01 CA168611/CA/NCI NIH HHS/United States ; R21 CA155649/CA/NCI NIH HHS/United States ; 1CA168611/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Humans ; Inflammation/immunology/*microbiology/*pathology ; *Microbiota ; Pancreatic Neoplasms/immunology/*microbiology/*pathology ; Risk Factors ; }, abstract = {Pancreatic cancer is one of the most lethal cancers worldwide. No effective screening methods exist, and available treatment modalities do not effectively treat the disease. Inflammatory conditions such as pancreatitis represent a well-known risk factor for pancreatic cancer development. Yet only in the past 2 decades has pancreatic cancer been recognized as an inflammation-driven cancer, and the precise mechanisms underlying the pathogenic role of inflammation are beginning to be explored in detail. A substantial amount of preclinical and clinical evidence suggests that bacteria are likely to influence this process by activating immune receptors and perpetuating cancer-associated inflammation. The recent explosion of investigations of the human microbiome have highlighted how perturbations of commensal bacterial populations can promote inflammation and promote disease processes, including carcinogenesis. The elucidation of the interplay between inflammation and microbiome in the context of pancreatic carcinogenesis will provide novel targets for intervention to prevent and treat pancreatic cancer more efficiently. Further studies toward this direction are urgently needed.}, }
@article {pmid24850265, year = {2014}, author = {Viaene, L and Thijs, L and Jin, Y and Liu, Y and Gu, Y and Meijers, B and Claes, K and Staessen, J and Evenepoel, P}, title = {Heritability and clinical determinants of serum indoxyl sulfate and p-cresyl sulfate, candidate biomarkers of the human microbiome enterotype.}, journal = {PloS one}, volume = {9}, number = {5}, pages = {e79682}, pmid = {24850265}, issn = {1932-6203}, mesh = {Adult ; Biomarkers/blood ; Cardiovascular Diseases/blood/genetics ; Cresols/*blood ; Cross-Sectional Studies ; Diet ; Female ; Humans ; Indican/*blood ; Male ; *Microbiota ; Middle Aged ; Sulfuric Acid Esters/*blood ; Young Adult ; }, abstract = {BACKGROUND: Indoxyl sulfate and p-cresyl sulfate are unique microbial co-metabolites. Both co-metabolites have been involved in the pathogenesis of accelerated cardiovascular disease and renal disease progression. Available evidence suggests that indoxyl sulfate and p-cresyl sulfate may be considered candidate biomarkers of the human enterotype and may help to explain the link between diet and cardiovascular disease burden.<br><br>OBJECTIVE AND DESIGN: Information on clinical determinants and heritability of indoxyl sulfate and p-cresyl sulfate serum is non-existing. To clarify this issue, the authors determined serum levels of indoxyl sulfate and p-cresyl sulfate in 773 individuals, recruited in the frame of the Flemish Study on Environment, Genes and Health Outcomes (FLEMENGHO study).<br><br>RESULTS: Serum levels of indoxyl sulfate and p-cresyl sulfate amounted to 3.1 (2.4-4.3) and 13.0 (7.4-21.5) &#x3bc;M, respectively. Regression analysis identified renal function, age and sex as independent determinants of both co-metabolites. Both serum indoxyl sulfate (h2&#x200a;=&#x200a;0.17) and p-cresyl sulfate (h2&#x200a;=&#x200a;0.18) concentrations showed moderate but significant heritability after adjustment for covariables, with significant genetic and environmental correlations for both co-metabolites.<br><br>LIMITATIONS: Family studies cannot provide conclusive evidence for a genetic contribution, as confounding by shared environmental effects can never be excluded.<br><br>CONCLUSIONS: The heritability of indoxyl sulfate and p-cresyl sulfate is moderate. Besides genetic host factors and environmental factors, also renal function, sex and age influence the serum levels of these co-metabolites.}, }
@article {pmid24846382, year = {2014}, author = {Ly, M and Abeles, SR and Boehm, TK and Robles-Sikisaka, R and Naidu, M and Santiago-Rodriguez, T and Pride, DT}, title = {Altered oral viral ecology in association with periodontal disease.}, journal = {mBio}, volume = {5}, number = {3}, pages = {e01133-14}, pmid = {24846382}, issn = {2150-7511}, support = {K08 AI085028/AI/NIAID NIH HHS/United States ; /WT_/Wellcome Trust/United Kingdom ; 1K08AI085028/AI/NIAID NIH HHS/United States ; }, mesh = {Adult ; Aged ; Bacteria/classification/genetics ; Biodiversity ; Biofilms ; Comorbidity ; Female ; Humans ; Male ; Metagenome ; Middle Aged ; Mouth/microbiology/*virology ; Periodontal Diseases/diagnosis/*virology ; RNA, Ribosomal, 16S ; RNA, Viral ; Risk Factors ; Saliva/virology ; Viruses/classification/genetics/isolation &amp; purification ; }, abstract = {UNLABELLED: The human oral cavity is home to a large and diverse community of viruses that have yet to be characterized in patients with periodontal disease. We recruited and sampled saliva and oral biofilm from a cohort of humans either periodontally healthy or with mild or significant periodontal disease to discern whether there are differences in viral communities that reflect their oral health status. We found communities of viruses inhabiting saliva and the subgingival and supragingival biofilms of each subject that were composed largely of bacteriophage. While there were homologous viruses common to different subjects and biogeographic sites, for most of the subjects, virome compositions were significantly associated with the oral sites from which they were derived. The largest distinctions between virome compositions were found when comparing the subgingival and supragingival biofilms to those of planktonic saliva. Differences in virome composition were significantly associated with oral health status for both subgingival and supragingival biofilm viruses but not for salivary viruses. Among the differences identified in virome compositions was a significant expansion of myoviruses in subgingival biofilm, suggesting that periodontal disease favors lytic phage. We also characterized the bacterial communities in each subject at each biogeographic site by using the V3 hypervariable segment of the 16S rRNA and did not identify distinctions between oral health and disease similar to those found in viral communities. The significantly altered ecology of viruses of oral biofilm in subjects with periodontal disease compared to that of relatively periodontally healthy ones suggests that viruses may serve as useful indicators of oral health status.<br><br>IMPORTANCE: Little is known about the role or the constituents of viruses as members of the human microbiome. We investigated the composition of human oral viral communities in a group of relatively periodontally healthy subjects or significant periodontitis to determine whether health status may be associated with differences in viruses. We found that most of the viruses present were predators of bacteria. The viruses inhabiting dental plaque were significantly different on the basis of oral health status, while those present in saliva were not. Dental plaque viruses in periodontitis were predicted to be significantly more likely to kill their bacterial hosts than those found in healthy mouths. Because oral diseases such as periodontitis have been shown to have altered bacterial communities, we believe that viruses and their role as drivers of ecosystem diversity are important contributors to the human oral microbiome in health and disease states.}, }
@article {pmid24846174, year = {2014}, author = {Hasan, NA and Young, BA and Minard-Smith, AT and Saeed, K and Li, H and Heizer, EM and McMillan, NJ and Isom, R and Abdullah, AS and Bornman, DM and Faith, SA and Choi, SY and Dickens, ML and Cebula, TA and Colwell, RR}, title = {Microbial community profiling of human saliva using shotgun metagenomic sequencing.}, journal = {PloS one}, volume = {9}, number = {5}, pages = {e97699}, pmid = {24846174}, issn = {1932-6203}, support = {1R01A139129-01//PHS HHS/United States ; 2R01A1039129-11A2//PHS HHS/United States ; }, mesh = {Adult ; Female ; Humans ; Male ; *Metagenome ; Metagenomics/*methods ; Microbiota/*genetics ; Saliva/*microbiology ; Sequence Analysis, DNA/*methods ; }, abstract = {Human saliva is clinically informative of both oral and general health. Since next generation shotgun sequencing (NGS) is now widely used to identify and quantify bacteria, we investigated the bacterial flora of saliva microbiomes of two healthy volunteers and five datasets from the Human Microbiome Project, along with a control dataset containing short NGS reads from bacterial species representative of the bacterial flora of human saliva. GENIUS, a system designed to identify and quantify bacterial species using unassembled short NGS reads was used to identify the bacterial species comprising the microbiomes of the saliva samples and datasets. Results, achieved within minutes and at greater than 90% accuracy, showed more than 175 bacterial species comprised the bacterial flora of human saliva, including bacteria known to be commensal human flora but also Haemophilus influenzae, Neisseria meningitidis, Streptococcus pneumoniae, and Gamma proteobacteria. Basic Local Alignment Search Tool (BLASTn) analysis in parallel, reported ca. five times more species than those actually comprising the in silico sample. Both GENIUS and BLAST analyses of saliva samples identified major genera comprising the bacterial flora of saliva, but GENIUS provided a more precise description of species composition, identifying to strain in most cases and delivered results at least 10,000 times faster. Therefore, GENIUS offers a facile and accurate system for identification and quantification of bacterial species and/or strains in metagenomic samples.}, }
@article {pmid24845653, year = {2014}, author = {Seth, S and Välimäki, N and Kaski, S and Honkela, A}, title = {Exploration and retrieval of whole-metagenome sequencing samples.}, journal = {Bioinformatics (Oxford, England)}, volume = {30}, number = {17}, pages = {2471-2479}, pmid = {24845653}, issn = {1367-4811}, mesh = {Algorithms ; Data Mining ; Diabetes Mellitus, Type 2/microbiology ; High-Throughput Nucleotide Sequencing ; Humans ; Inflammatory Bowel Diseases/microbiology ; Metagenomics/*methods ; Microbiota ; Sequence Analysis, DNA ; }, abstract = {MOTIVATION: Over the recent years, the field of whole-metagenome shotgun sequencing has witnessed significant growth owing to the high-throughput sequencing technologies that allow sequencing genomic samples cheaper, faster and with better coverage than before. This technical advancement has initiated the trend of sequencing multiple samples in different conditions or environments to explore the similarities and dissimilarities of the microbial communities. Examples include the human microbiome project and various studies of the human intestinal tract. With the availability of ever larger databases of such measurements, finding samples similar to a given query sample is becoming a central operation.<br><br>RESULTS: In this article, we develop a content-based exploration and retrieval method for whole-metagenome sequencing samples. We apply a distributed string mining framework to efficiently extract all informative sequence k-mers from a pool of metagenomic samples and use them to measure the dissimilarity between two samples. We evaluate the performance of the proposed approach on two human gut metagenome datasets as well as human microbiome project metagenomic samples. We observe significant enrichment for diseased gut samples in results of queries with another diseased sample and high accuracy in discriminating between different body sites even though the method is unsupervised.<br><br>A software implementation of the DSM framework is available at https://github.com/HIITMetagenomics/dsm-framework.<br><br>SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.}, }
@article {pmid24843156, year = {2014}, author = {Franzosa, EA and Morgan, XC and Segata, N and Waldron, L and Reyes, J and Earl, AM and Giannoukos, G and Boylan, MR and Ciulla, D and Gevers, D and Izard, J and Garrett, WS and Chan, AT and Huttenhower, C}, title = {Relating the metatranscriptome and metagenome of the human gut.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {111}, number = {22}, pages = {E2329-38}, pmid = {24843156}, issn = {1091-6490}, support = {R01 CA166150/CA/NCI NIH HHS/United States ; P30 DK043351/DK/NIDDK NIH HHS/United States ; R01 CA137178/CA/NCI NIH HHS/United States ; P30 DK034854/DK/NIDDK NIH HHS/United States ; R01 HG005969/HG/NHGRI NIH HHS/United States ; CA166150/CA/NCI NIH HHS/United States ; U54 DK102557/DK/NIDDK NIH HHS/United States ; HHSN272200900018C/AI/NIAID NIH HHS/United States ; P50 CA127003/CA/NCI NIH HHS/United States ; U19 AI110818/AI/NIAID NIH HHS/United States ; }, mesh = {DNA, Bacterial/analysis ; Feces/microbiology ; Gastrointestinal Tract/*microbiology/physiology ; Gene Expression Regulation, Bacterial ; Genomics/*methods ; Humans ; Metagenome/*genetics ; Microbiota/*genetics ; Mouth/microbiology ; RNA, Bacterial/analysis ; Saliva/microbiology ; Specimen Handling/methods ; Transcriptome/*genetics ; }, abstract = {Although the composition of the human microbiome is now well-studied, the microbiota's >8 million genes and their regulation remain largely uncharacterized. This knowledge gap is in part because of the difficulty of acquiring large numbers of samples amenable to functional studies of the microbiota. We conducted what is, to our knowledge, one of the first human microbiome studies in a well-phenotyped prospective cohort incorporating taxonomic, metagenomic, and metatranscriptomic profiling at multiple body sites using self-collected samples. Stool and saliva were provided by eight healthy subjects, with the former preserved by three different methods (freezing, ethanol, and RNAlater) to validate self-collection. Within-subject microbial species, gene, and transcript abundances were highly concordant across sampling methods, with only a small fraction of transcripts (<5%) displaying between-method variation. Next, we investigated relationships between the oral and gut microbial communities, identifying a subset of abundant oral microbes that routinely survive transit to the gut, but with minimal transcriptional activity there. Finally, systematic comparison of the gut metagenome and metatranscriptome revealed that a substantial fraction (41%) of microbial transcripts were not differentially regulated relative to their genomic abundances. Of the remainder, consistently underexpressed pathways included sporulation and amino acid biosynthesis, whereas up-regulated pathways included ribosome biogenesis and methanogenesis. Across subjects, metatranscriptional profiles were significantly more individualized than DNA-level functional profiles, but less variable than microbial composition, indicative of subject-specific whole-community regulation. The results thus detail relationships between community genomic potential and gene expression in the gut, and establish the feasibility of metatranscriptomic investigations in subject-collected and shipped samples.}, }
@article {pmid24827833, year = {2014}, author = {Kraal, L and Abubucker, S and Kota, K and Fischbach, MA and Mitreva, M}, title = {The prevalence of species and strains in the human microbiome: a resource for experimental efforts.}, journal = {PloS one}, volume = {9}, number = {5}, pages = {e97279}, pmid = {24827833}, issn = {1932-6203}, support = {DP2 OD007290/OD/NIH HHS/United States ; T32 GM067547/GM/NIGMS NIH HHS/United States ; P50 GM081879/GM/NIGMS NIH HHS/United States ; T32 EB009383/EB/NIBIB NIH HHS/United States ; U54 HG004968/HG/NHGRI NIH HHS/United States ; U54 HG003079/HG/NHGRI NIH HHS/United States ; U54HG004968/HG/NHGRI NIH HHS/United States ; }, mesh = {Genome, Bacterial/*genetics ; Humans ; Metagenome/genetics ; Metagenomics/methods ; Microbiota/*genetics ; Phylogeny ; Prevalence ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA/methods ; }, abstract = {Experimental efforts to characterize the human microbiota often use bacterial strains that were chosen for historical rather than biological reasons. Here, we report an analysis of 380 whole-genome shotgun samples from 100 subjects from the NIH Human Microbiome Project. By mapping their reads to 1,751 reference genome sequences and analyzing the resulting relative strain abundance in each sample we present metrics and visualizations that can help identify strains of interest for experimentalists. We also show that approximately 14 strains of 10 species account for 80% of the mapped reads from a typical stool sample, indicating that the function of a community may not be irreducibly complex. Some of these strains account for >20% of the sequence reads in a subset of samples but are absent in others, a dichotomy that could underlie biological differences among subjects. These data should serve as an important strain selection resource for the community of researchers who take experimental approaches to studying the human microbiota.}, }
@article {pmid24817404, year = {2014}, author = {Hospodsky, D and Pickering, AJ and Julian, TR and Miller, D and Gorthala, S and Boehm, AB and Peccia, J}, title = {Hand bacterial communities vary across two different human populations.}, journal = {Microbiology (Reading, England)}, volume = {160}, number = {Pt 6}, pages = {1144-1152}, doi = {10.1099/mic.0.075390-0}, pmid = {24817404}, issn = {1465-2080}, mesh = {Bacteria/*classification/*genetics ; DNA, Bacterial/chemistry/genetics ; DNA, Ribosomal/chemistry/genetics ; Female ; Hand/*microbiology ; Humans ; *Microbiota ; Molecular Sequence Data ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; Tanzania ; United States ; }, abstract = {This study utilized pyrosequencing-based phylogenetic library results to assess bacterial communities on the hands of women in Tanzania and compared these communities with bacteria assemblages on the hands of US women. Bacterial population profiles and phylogenetically based ordinate analysis demonstrated that the bacterial communities on hands were more similar for selected populations within a country than between the two countries considered. Organisms that have commonly been identified in prior human skin microbiome studies, including members of the Propionibacteriaceae, Staphylococcaceae and Streptococceacea families, were highly abundant on US hands and drove the clustering of US hand microbial communities into a distinct group. The most abundant bacterial taxa on Tanzanian hands were the soil-associated Rhodobacteraceae and Nocardioidaceae. These results help to expand human microbiome results beyond US and European populations, and the identification and abundance of soil-associated bacteria on Tanzanian hands demonstrated the important role of the environment in shaping the microbial communities on human hands.}, }
@article {pmid24816793, year = {2014}, author = {Wu, J and Guo, H and Yi, G and Zhou, L and He, X and Huang, X and Wang, H and Xue, W and Xu, J}, title = {Prevalent drug resistance among oral yeasts from asymptomatic patients in Hainan, China.}, journal = {Mycopathologia}, volume = {177}, number = {5-6}, pages = {299-307}, pmid = {24816793}, issn = {1573-0832}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Antifungal Agents/*pharmacology ; Asymptomatic Diseases ; Candidiasis, Oral/diagnosis/*microbiology ; Child ; Child, Preschool ; China ; *Drug Resistance, Fungal ; Female ; Humans ; Male ; Microbial Sensitivity Tests ; Middle Aged ; Mouth/*microbiology ; Yeasts/classification/*drug effects/genetics/*isolation &amp; purification ; Young Adult ; }, abstract = {The oral cavity is a significant niche of the human microbiome and a gateway for the microbiota in many other human body sites. As a result, understanding the oral microbiota has broad implications for the prevention and management of human infectious diseases. Opportunistic yeast infections are among the most prevalent fungal infections of humans, and most opportunistic yeast pathogens are common residents of the oral mucosa. However, relatively little is known about the drug susceptibility profiles of oral yeasts. Here, we report the species distribution and patterns of antifungal susceptibility profiles among 313 yeasts isolated from the oral cavities of 301 asymptomatic hospitalized patients in Hainan Province in southern China. These yeasts were tested for their susceptibilities to the following five drugs: amphotericin B, fluconazole, itraconazole, ketoconazole, and fluorocytosine. Since none of the sampled hosts had taken any antifungal drugs at least 3 months before samples were taken, we hypothesized that little or no drug resistance should be observed. Contrary to our expectations, our analyses identified that 29 % (91/313) of the isolates were resistant to at least one drug and 14.3 % (45/313) were resistant to two or more of the five common drugs. The potential sources of the observed resistance were discussed.}, }
@article {pmid24804518, year = {2014}, author = {Tow, J}, title = {Heal the mother, heal the baby: epigenetics, breastfeeding and the human microbiome.}, journal = {Breastfeeding review : professional publication of the Nursing Mothers' Association of Australia}, volume = {22}, number = {1}, pages = {7-9}, pmid = {24804518}, issn = {0729-2759}, mesh = {*Breast Feeding ; *Epigenesis, Genetic ; Female ; Gastrointestinal Tract/immunology ; Humans ; *Immunity, Maternally-Acquired ; Infant, Newborn ; Microbiota/*immunology ; Milk, Human/*immunology ; }, }
@article {pmid24800639, year = {2014}, author = {Pleil, JD and Miekisch, W and Stiegel, MA and Beauchamp, J}, title = {Extending breath analysis to the cellular level: current thoughts on the human microbiome and the expression of organic compounds in the human exposome.}, journal = {Journal of breath research}, volume = {8}, number = {2}, pages = {029001}, doi = {10.1088/1752-7155/8/2/029001}, pmid = {24800639}, issn = {1752-7163}, mesh = {Bacterial Infections/diagnosis ; Biomarkers/metabolism ; Breath Tests/*methods ; *Exhalation ; Humans ; Metabolome ; *Microbiota ; Volatile Organic Compounds/*analysis ; }, }
@article {pmid24797966, year = {2014}, author = {Blum, HE}, title = {Advances in individualized and regenerative medicine.}, journal = {Advances in medical sciences}, volume = {59}, number = {1}, pages = {7-12}, doi = {10.1016/j.advms.2013.12.001}, pmid = {24797966}, issn = {1898-4002}, mesh = {Adult ; *Genetic Therapy ; *Genome, Human ; Humans ; Induced Pluripotent Stem Cells/*cytology ; *Precision Medicine ; *Regenerative Medicine ; }, abstract = {Molecular and cell biology have resulted in major advances in our understanding of disease pathogenesis as well as in novel strategies for the diagnosis, therapy and prevention of human diseases. Based on modern molecular, genetic and biochemical methodologies it is on the one hand possible to identify for example disease-related point mutations and single nucleotide polymorphisms. On the other hand, using high throughput array and other technologies, it is for example possible to simultaneously analyze thousands of genes or gene products (RNA and proteins), resulting in an individual gene or gene expression profile ('signature'). Such data increasingly allow to define the individual disposition for a given disease and to predict disease prognosis as well as the efficacy of therapeutic strategies in the individual patient ('individualized medicine'). At the same time, the basic discoveries in cell biology, including embryonic and adult stem cells, induced pluripotent stem cells, genetically modified cells and others, have moved regenerative medicine into the center of biomedical research worldwide with a major translational impact on tissue engineering as well as transplantation medicine. All these aspects have greatly contributed to the recent advances in regenerative medicine and the development novel concepts for the treatment of many human diseases, including liver diseases.}, }
@article {pmid24785449, year = {2014}, author = {ElRakaiby, M and Dutilh, BE and Rizkallah, MR and Boleij, A and Cole, JN and Aziz, RK}, title = {Pharmacomicrobiomics: the impact of human microbiome variations on systems pharmacology and personalized therapeutics.}, journal = {Omics : a journal of integrative biology}, volume = {18}, number = {7}, pages = {402-414}, pmid = {24785449}, issn = {1557-8100}, mesh = {Animals ; Anti-Infective Agents/pharmacology/therapeutic use ; Biodiversity ; Genomics ; Humans ; *Metagenome ; Microbiology/trends ; *Microbiota ; *Pharmacogenetics ; *Precision Medicine ; }, abstract = {The Human Microbiome Project (HMP) is a global initiative undertaken to identify and characterize the collection of human-associated microorganisms at multiple anatomic sites (skin, mouth, nose, colon, vagina), and to determine how intra-individual and inter-individual alterations in the microbiome influence human health, immunity, and different disease states. In this review article, we summarize the key findings and applications of the HMP that may impact pharmacology and personalized therapeutics. We propose a microbiome cloud model, reflecting the temporal and spatial uncertainty of defining an individual's microbiome composition, with examples of how intra-individual variations (such as age and mode of delivery) shape the microbiome structure. Additionally, we discuss how this microbiome cloud concept explains the difficulty to define a core human microbiome and to classify individuals according to their biome types. Detailed examples are presented on microbiome changes related to colorectal cancer, antibiotic administration, and pharmacomicrobiomics, or drug-microbiome interactions, highlighting how an improved understanding of the human microbiome, and alterations thereof, may lead to the development of novel therapeutic agents, the modification of antibiotic policies and implementation, and improved health outcomes. Finally, the prospects of a collaborative computational microbiome research initiative in Africa are discussed.}, }
@article {pmid24777677, year = {2013}, author = {Kostic, AD and Chun, E and Meyerson, M and Garrett, WS}, title = {Microbes and inflammation in colorectal cancer.}, journal = {Cancer immunology research}, volume = {1}, number = {3}, pages = {150-157}, doi = {10.1158/2326-6066.CIR-13-0101}, pmid = {24777677}, issn = {2326-6074}, mesh = {Carcinogenesis ; Colorectal Neoplasms/*immunology/*microbiology ; Gastrointestinal Tract/immunology/*microbiology ; Host-Pathogen Interactions ; Humans ; Inflammation/microbiology ; *Microbiota ; Mucous Membrane ; Tumor Microenvironment ; }, abstract = {Over the past decade, there has been a renaissance in research on physiologic interactions between humans and their resident microbiota, the vast numbers of bacteria, fungi, and viruses that live within and on the body. The burgeoning interest in what constitutes the human microbiome has also focused on the contribution of microbes to carcinogenesis. Given the microbiomes of malignancies arising at mucosal sites, the microbiota may prove as influential as stromal cells and immune cells in the tumor microenvironment. Herein, we focus on the interconnections of microbes and inflammation in colorectal carcinogenesis.}, }
@article {pmid24757212, year = {2014}, author = {Vital, M and Howe, AC and Tiedje, JM}, title = {Revealing the bacterial butyrate synthesis pathways by analyzing (meta)genomic data.}, journal = {mBio}, volume = {5}, number = {2}, pages = {e00889}, pmid = {24757212}, issn = {2150-7511}, support = {UH3 DK083993/DK/NIDDK NIH HHS/United States ; }, mesh = {Bacteria/*genetics/*metabolism ; Butyrates/*metabolism ; Feces/*microbiology ; Healthy Volunteers ; Humans ; Metabolic Networks and Pathways/*genetics ; *Metagenomics ; *Microbiota ; }, abstract = {Butyrate-producing bacteria have recently gained attention, since they are important for a healthy colon and when altered contribute to emerging diseases, such as ulcerative colitis and type II diabetes. This guild is polyphyletic and cannot be accurately detected by 16S rRNA gene sequencing. Consequently, approaches targeting the terminal genes of the main butyrate-producing pathway have been developed. However, since additional pathways exist and alternative, newly recognized enzymes catalyzing the terminal reaction have been described, previous investigations are often incomplete. We undertook a broad analysis of butyrate-producing pathways and individual genes by screening 3,184 sequenced bacterial genomes from the Integrated Microbial Genome database. Genomes of 225 bacteria with a potential to produce butyrate were identified, including many previously unknown candidates. The majority of candidates belong to distinct families within the Firmicutes, but members of nine other phyla, especially from Actinobacteria, Bacteroidetes, Fusobacteria, Proteobacteria, Spirochaetes, and Thermotogae, were also identified as potential butyrate producers. The established gene catalogue (3,055 entries) was used to screen for butyrate synthesis pathways in 15 metagenomes derived from stool samples of healthy individuals provided by the HMP (Human Microbiome Project) consortium. A high percentage of total genomes exhibited a butyrate-producing pathway (mean, 19.1%; range, 3.2% to 39.4%), where the acetyl-coenzyme A (CoA) pathway was the most prevalent (mean, 79.7% of all pathways), followed by the lysine pathway (mean, 11.2%). Diversity analysis for the acetyl-CoA pathway showed that the same few firmicute groups associated with several Lachnospiraceae and Ruminococcaceae were dominating in most individuals, whereas the other pathways were associated primarily with Bacteroidetes. IMPORTANCE Microbiome research has revealed new, important roles of our gut microbiota for maintaining health, but an understanding of effects of specific microbial functions on the host is in its infancy, partly because in-depth functional microbial analyses are rare and publicly available databases are often incomplete/misannotated. In this study, we focused on production of butyrate, the main energy source for colonocytes, which plays a critical role in health and disease. We have provided a complete database of genes from major known butyrate-producing pathways, using in-depth genomic analysis of publicly available genomes, filling an important gap to accurately assess the butyrate-producing potential of complex microbial communities from "-omics"-derived data. Furthermore, a reference data set containing the abundance and diversity of butyrate synthesis pathways from the healthy gut microbiota was established through a metagenomics-based assessment. This study will help in understanding the role of butyrate producers in health and disease and may assist the development of treatments for functional dysbiosis.}, }
@article {pmid24751579, year = {2014}, author = {Tyler, AD and Smith, MI and Silverberg, MS}, title = {Analyzing the human microbiome: a "how to" guide for physicians.}, journal = {The American journal of gastroenterology}, volume = {109}, number = {7}, pages = {983-993}, doi = {10.1038/ajg.2014.73}, pmid = {24751579}, issn = {1572-0241}, mesh = {Computational Biology/*methods ; Gastrointestinal Tract/*microbiology ; High-Throughput Nucleotide Sequencing/*methods ; Humans ; Metagenomics/*methods ; *Microbiota ; Phylogeny ; }, abstract = {The application of high-throughput next-generation sequencing to the analysis of the human microbiome has led to a shift in our understanding of the etiology of complex diseases. In consequence, a great deal of literature can now be found exploring this complex system, and reviewing recent findings. Observations of alterations in the intestinal microbiome associating with inflammatory bowel disease and other chronic conditions are well supported and have been widely accepted by the research community. Yet, it can be difficult to objectively evaluate the importance of these results, given the wide variety of methodologies applied by different groups in the field. The aim of this review is to focus attention on the basic principles involved in microbiome analyses, and to describe factors that may have an impact on the accurate interpretation of results.}, }
@article {pmid24739969, year = {2014}, author = {Ding, T and Schloss, PD}, title = {Dynamics and associations of microbial community types across the human body.}, journal = {Nature}, volume = {509}, number = {7500}, pages = {357-360}, pmid = {24739969}, issn = {1476-4687}, support = {R01 HG005975/HG/NHGRI NIH HHS/United States ; P30 DK034933/DK/NIDDK NIH HHS/United States ; R01HG005975/HG/NHGRI NIH HHS/United States ; R01GM099514/GM/NIGMS NIH HHS/United States ; P30DK034933/DK/NIDDK NIH HHS/United States ; R01 GM099514/GM/NIGMS NIH HHS/United States ; }, mesh = {Breast Feeding ; Disease Susceptibility ; Educational Status ; Feces/microbiology ; Female ; Gastrointestinal Tract/microbiology ; Health ; *Human Body ; Humans ; Life Style ; Male ; Metagenome/genetics ; *Microbiota/genetics ; Mouth/microbiology ; *Organ Specificity ; Precision Medicine ; RNA, Ribosomal, 16S/genetics ; Sex Characteristics ; Time Factors ; Vagina/microbiology ; }, abstract = {A primary goal of the Human Microbiome Project (HMP) was to provide a reference collection of 16S ribosomal RNA gene sequences collected from sites across the human body that would allow microbiologists to better associate changes in the microbiome with changes in health. The HMP Consortium has reported the structure and function of the human microbiome in 300 healthy adults at 18 body sites from a single time point. Using additional data collected over the course of 12-18 months, we used Dirichlet multinomial mixture models to partition the data into community types for each body site and made three important observations. First, there were strong associations between whether individuals had been breastfed as an infant, their gender, and their level of education with their community types at several body sites. Second, although the specific taxonomic compositions of the oral and gut microbiomes were different, the community types observed at these sites were predictive of each other. Finally, over the course of the sampling period, the community types from sites within the oral cavity were the least stable, whereas those in the vagina and gut were the most stable. Our results demonstrate that even with the considerable intra- and interpersonal variation in the human microbiome, this variation can be partitioned into community types that are predictive of each other and are probably the result of life-history characteristics. Understanding the diversity of community types and the mechanisms that result in an individual having a particular type or changing types, will allow us to use their community types to assess disease risk and to personalize therapies.}, }
@article {pmid24736157, year = {2014}, author = {De Monte, S and Rainey, PB}, title = {Nascent multicellular life and the emergence of individuality.}, journal = {Journal of biosciences}, volume = {39}, number = {2}, pages = {237-248}, pmid = {24736157}, issn = {0973-7138}, mesh = {*Biological Evolution ; Humans ; Microbial Interactions ; Models, Biological ; Population Dynamics ; Selection, Genetic ; }, abstract = {The evolution of multicellular organisms from unicellular ancestors involves a shift in the level at which selection operates. It is usual to think about this shift in terms of the emergence of traits that cause heritable differences in reproductive output at the level of nascent collectives. Defining these traits and the causes of their origin lies at the heart of understanding the evolution of multicellular life. In working toward a mechanistic, take-nothing-for-granted account, we begin by recognizing that the standard Lewontin formulation of properties necessary and sufficient for evolution by natural selection does not necessarily encompass Darwinian evolution in primitive collectives where parent-offspring relationships may have been poorly defined. This, we suggest, limits the ability to conceptualize and capture the earliest manifestations of Darwinian properties. By way of solution we propose a relaxed interpretation of Lewontin's conditions and present these in the form of a set of necessary requirements for evolution by natural selection based upon the establishment of genealogical connections between recurrences of collectives. With emphasis on genealogy - as opposed to reproduction - it is possible to conceive selection acting on collectives prior to any manifestation of heritable variance in fitness. Such possibility draws attention to the evolutionary emergence of traits that strengthen causal relationships between recurrences - traits likely to underpin the emergence of forms of multiplication that establish parent-offspring relationships. Application of this framework to collectives of marginal status, particularly those whose recurrence is not defined by genealogy, makes clear that change at the level of collectives need not arise from selection acting at the higher level. We conclude by outlining applicability of our framework to loosely defined collectives of cells, such as those comprising the slugs of social amoeba and microbes that constitute the human microbiome.}, }
@article {pmid24713325, year = {2014}, author = {Syed, AK and Ghosh, S and Love, NG and Boles, BR}, title = {Triclosan promotes Staphylococcus aureus nasal colonization.}, journal = {mBio}, volume = {5}, number = {2}, pages = {e01015}, pmid = {24713325}, issn = {2150-7511}, support = {R01 AI099065/AI/NIAID NIH HHS/United States ; }, mesh = {Adult ; Animals ; Anti-Infective Agents, Local/*metabolism ; Bacterial Adhesion/drug effects ; Carrier State/*microbiology ; Humans ; Nasal Cavity/*microbiology ; Rats ; Sigmodontinae ; Staphylococcal Infections/*microbiology ; Staphylococcus aureus/*drug effects/growth &amp; development ; Triclosan/*metabolism ; }, abstract = {The biocide triclosan is used in many personal care products, including toothpastes, soaps, clothing, and medical equipment. Consequently, it is present as a contaminant in the environment and has been detected in some human fluids, including serum, urine, and milk. Staphylococcus aureus is an opportunistic pathogen that colonizes the noses and throats of approximately 30% of the population. Colonization with S. aureus is known to be a risk factor for several types of infection. Here we demonstrate that triclosan is commonly found in the nasal secretions of healthy adults and the presence of triclosan trends positively with nasal colonization by S. aureus. We demonstrate that triclosan can promote the binding of S. aureus to host proteins such as collagen, fibronectin, and keratin, as well as inanimate surfaces such as plastic and glass. Lastly, triclosan-exposed rats are more susceptible to nasal colonization with S. aureus. These data reveal a novel factor that influences the ability of S. aureus to bind surfaces and alters S. aureus nasal colonization. IMPORTANCE Triclosan has been used as a biocide for over 40 years, but the broader effects that it has on the human microbiome have not been investigated. We demonstrate that triclosan is present in nasal secretions of a large portion of a test population and its presence correlates with Staphylococcus aureus nasal colonization. Triclosan also promotes the binding of S. aureus to human proteins and increases the susceptibility of rats to nasal colonization by S. aureus. These findings are significant because S. aureus colonization is a known risk factor for the development of several types of infections. Our data demonstrate the unintended consequences of unregulated triclosan use and contribute to the growing body of research demonstrating inadvertent effects of triclosan on the environment and human health.}, }
@article {pmid24708091, year = {2014}, author = {Kidd, JM and Sharpton, TJ and Bobo, D and Norman, PJ and Martin, AR and Carpenter, ML and Sikora, M and Gignoux, CR and Nemat-Gorgani, N and Adams, A and Guadalupe, M and Guo, X and Feng, Q and Li, Y and Liu, X and Parham, P and Hoal, EG and Feldman, MW and Pollard, KS and Wall, JD and Bustamante, CD and Henn, BM}, title = {Exome capture from saliva produces high quality genomic and metagenomic data.}, journal = {BMC genomics}, volume = {15}, number = {}, pages = {262}, pmid = {24708091}, issn = {1471-2164}, support = {R01HG003229/HG/NHGRI NIH HHS/United States ; T32HG000044/HG/NHGRI NIH HHS/United States ; GM007790/GM/NIGMS NIH HHS/United States ; R01 AI017892/AI/NIAID NIH HHS/United States ; T32GM007175/GM/NIGMS NIH HHS/United States ; R01HG400409/HG/NHGRI NIH HHS/United States ; T32 HG000044/HG/NHGRI NIH HHS/United States ; T32 GM007790/GM/NIGMS NIH HHS/United States ; DP5 OD009154/OD/NIH HHS/United States ; AI17892/AI/NIAID NIH HHS/United States ; 1DP5OD009154/OD/NIH HHS/United States ; }, mesh = {*Exome ; Genome, Human ; *Genomics ; Genotype ; HLA Antigens/genetics ; High-Throughput Nucleotide Sequencing/methods ; Humans ; *Metagenomics ; Microbiota ; Molecular Sequence Data ; Mouth/microbiology ; Polymorphism, Single Nucleotide ; Quantitative Trait Loci ; Receptors, KIR/genetics ; Saliva/*chemistry/*microbiology ; }, abstract = {BACKGROUND: Targeted capture of genomic regions reduces sequencing cost while generating higher coverage by allowing biomedical researchers to focus on specific loci of interest, such as exons. Targeted capture also has the potential to facilitate the generation of genomic data from DNA collected via saliva or buccal cells. DNA samples derived from these cell types tend to have a lower human DNA yield, may be degraded from age and/or have contamination from bacteria or other ambient oral microbiota. However, thousands of samples have been previously collected from these cell types, and saliva collection has the advantage that it is a non-invasive and appropriate for a wide variety of research.<br><br>RESULTS: We demonstrate successful enrichment and sequencing of 15 South African KhoeSan exomes and 2 full genomes with samples initially derived from saliva. The expanded exome dataset enables us to characterize genetic diversity free from ascertainment bias for multiple KhoeSan populations, including new exome data from six HGDP Namibian San, revealing substantial population structure across the Kalahari Desert region. Additionally, we discover and independently verify thirty-one previously unknown KIR alleles using methods we developed to accurately map and call the highly polymorphic HLA and KIR loci from exome capture data. Finally, we show that exome capture of saliva-derived DNA yields sufficient non-human sequences to characterize oral microbial communities, including detection of bacteria linked to oral disease (e.g. Prevotella melaninogenica). For comparison, two samples were sequenced using standard full genome library preparation without exome capture and we found no systematic bias of metagenomic information between exome-captured and non-captured data.<br><br>CONCLUSIONS: DNA from human saliva samples, collected and extracted using standard procedures, can be used to successfully sequence high quality human exomes, and metagenomic data can be derived from non-human reads. We find that individuals from the Kalahari carry a higher oral pathogenic microbial load than samples surveyed in the Human Microbiome Project. Additionally, rare variants present in the exomes suggest strong population structure across different KhoeSan populations.}, }
@article {pmid24694284, year = {2014}, author = {Ma, J and Coarfa, C and Qin, X and Bonnen, PE and Milosavljevic, A and Versalovic, J and Aagaard, K}, title = {mtDNA haplogroup and single nucleotide polymorphisms structure human microbiome communities.}, journal = {BMC genomics}, volume = {15}, number = {}, pages = {257}, pmid = {24694284}, issn = {1471-2164}, mesh = {DNA, Mitochondrial/*genetics ; *Haplotypes ; Humans ; *Microbiota ; *Polymorphism, Single Nucleotide ; }, abstract = {BACKGROUND: Although our microbial community and genomes (the human microbiome) outnumber our genome by several orders of magnitude, to what extent the human host genetic complement informs the microbiota composition is not clear. The Human Microbiome Project (HMP) Consortium established a unique population-scale framework with which to characterize the relationship of microbial community structure with their human hosts. A wide variety of taxa and metabolic pathways have been shown to be differentially distributed by virtue of race/ethnicity in the HMP. Given that mtDNA haplogroups are the maternally derived ancestral genomic markers and mitochondria's role as the generator for cellular ATP, characterizing the relationship between human mtDNA genomic variants and microbiome profiles becomes of potential marked biologic and clinical interest.<br><br>RESULTS: We leveraged sequencing data from the HMP to investigate the association between microbiome community structures with its own host mtDNA variants. 15 haplogroups and 631 mtDNA nucleotide polymorphisms (mean sequencing depth of 280X on the mitochondria genome) from 89 individuals participating in the HMP were accurately identified. 16S rRNA (V3-V5 region) sequencing generated microbiome taxonomy profiles and whole genome shotgun sequencing generated metabolic profiles from various body sites were treated as traits to conduct association analysis between haplogroups and host clinical metadata through linear regression. The mtSNPs of individuals with European haplogroups were associated with microbiome profiles using PLINK quantitative trait associations with permutation and adjusted for multiple comparisons. We observe that among 139 stool and 59 vaginal posterior fornix samples, several haplogroups show significant association with specific microbiota (q-value < 0.05) as well as their aggregate community structure (Chi-square with Monte Carlo, p < 0.005), which confirmed and expanded previous research on the association of race and ethnicity with microbiome profile. Our results further indicate that mtDNA variations may render different microbiome profiles, possibly through an inflammatory response to different levels of reactive oxygen species activity.<br><br>CONCLUSIONS: These data provide initial evidence for the association between host ancestral genome with the structure of its microbiome.}, }
@article {pmid24692635, year = {2014}, author = {Jorth, P and Turner, KH and Gumus, P and Nizam, N and Buduneli, N and Whiteley, M}, title = {Metatranscriptomics of the human oral microbiome during health and disease.}, journal = {mBio}, volume = {5}, number = {2}, pages = {e01012-14}, pmid = {24692635}, issn = {2150-7511}, support = {F31 DE021633/DE/NIDCR NIH HHS/United States ; R01 DE023193/DE/NIDCR NIH HHS/United States ; 5F31DE021633-02/DE/NIDCR NIH HHS/United States ; 1R01DE020100/DE/NIDCR NIH HHS/United States ; R01 DE020100/DE/NIDCR NIH HHS/United States ; }, mesh = {Adult ; Dysbiosis ; Female ; Humans ; Male ; *Metagenome ; *Microbiota ; Mouth/*microbiology ; Periodontitis/microbiology ; *Transcriptome ; }, abstract = {The human microbiome plays important roles in health, but when disrupted, these same indigenous microbes can cause disease. The composition of the microbiome changes during the transition from health to disease; however, these changes are often not conserved among patients. Since microbiome-associated diseases like periodontitis cause similar patient symptoms despite interpatient variability in microbial community composition, we hypothesized that human-associated microbial communities undergo conserved changes in metabolism during disease. Here, we used patient-matched healthy and diseased samples to compare gene expression of 160,000 genes in healthy and diseased periodontal communities. We show that health- and disease-associated communities exhibit defined differences in metabolism that are conserved between patients. In contrast, the metabolic gene expression of individual species was highly variable between patients. These results demonstrate that despite high interpatient variability in microbial composition, disease-associated communities display conserved metabolic profiles that are generally accomplished by a patient-specific cohort of microbes. IMPORTANCE The human microbiome project has shown that shifts in our microbiota are associated with many diseases, including obesity, Crohn's disease, diabetes, and periodontitis. While changes in microbial populations are apparent during these diseases, the species associated with each disease can vary from patient to patient. Taking into account this interpatient variability, we hypothesized that specific microbiota-associated diseases would be marked by conserved microbial community behaviors. Here, we use gene expression analyses of patient-matched healthy and diseased human periodontal plaque to show that microbial communities have highly conserved metabolic gene expression profiles, whereas individual species within the community do not. Furthermore, disease-associated communities exhibit conserved changes in metabolic and virulence gene expression.}, }
@article {pmid24676219, year = {2014}, author = {Pyles, RB and Vincent, KL and Baum, MM and Elsom, B and Miller, AL and Maxwell, C and Eaves-Pyles, TD and Li, G and Popov, VL and Nusbaum, RJ and Ferguson, MR}, title = {Cultivated vaginal microbiomes alter HIV-1 infection and antiretroviral efficacy in colonized epithelial multilayer cultures.}, journal = {PloS one}, volume = {9}, number = {3}, pages = {e93419}, pmid = {24676219}, issn = {1932-6203}, support = {UL1TR000071/TR/NCATS NIH HHS/United States ; R01AI100744/AI/NIAID NIH HHS/United States ; UL1 TR000071/TR/NCATS NIH HHS/United States ; P30 AI036211/AI/NIAID NIH HHS/United States ; R01 AI100744/AI/NIAID NIH HHS/United States ; }, mesh = {Adult ; Anti-HIV Agents/pharmacology ; Cell Culture Techniques ; Cell Line ; Cytokines/biosynthesis/metabolism ; Epithelial Cells/drug effects/*microbiology/virology ; Female ; HIV-1/*physiology ; Host-Pathogen Interactions ; Humans ; Microbiota/*physiology ; Models, Biological ; Mucous Membrane/drug effects/*microbiology/virology ; Vagina/microbiology/virology ; Virus Replication/drug effects ; }, abstract = {There is a pressing need for modeling of the symbiotic and at times dysbiotic relationship established between bacterial microbiomes and human mucosal surfaces. In particular clinical studies have indicated that the complex vaginal microbiome (VMB) contributes to the protection against sexually-transmitted pathogens including the life-threatening human immunodeficiency virus (HIV-1). The human microbiome project has substantially increased our understanding of the complex bacterial communities in the vagina however, as is the case for most microbiomes, very few of the community member species have been successfully cultivated in the laboratory limiting the types of studies that can be completed. A genetically controlled ex vivo model system is critically needed to study the complex interactions and associated molecular dialog. We present the first vaginal mucosal culture model that supports colonization by both healthy and dysbiotic VMB from vaginal swabs collected from routine gynecological patients. The immortalized vaginal epithelial cells used in the model and VMB cryopreservation methods provide the opportunity to reproducibly create replicates for lab-based evaluations of this important mucosal/bacterial community interface. The culture system also contains HIV-1 susceptible cells allowing us to study the impact of representative microbiomes on replication. Our results show that our culture system supports stable and reproducible colonization by VMB representing distinct community state types and that the selected representatives have significantly different effects on the replication of HIV-1. Further, we show the utility of the system to predict unwanted alterations in efficacy or bacterial community profiles following topical application of a front line antiretroviral.}, }
@article {pmid24643867, year = {2014}, author = {Quinn, RA and Lim, YW and Maughan, H and Conrad, D and Rohwer, F and Whiteson, KL}, title = {Biogeochemical forces shape the composition and physiology of polymicrobial communities in the cystic fibrosis lung.}, journal = {mBio}, volume = {5}, number = {2}, pages = {e00956-13}, pmid = {24643867}, issn = {2150-7511}, support = {R01 GM095384/GM/NIGMS NIH HHS/United States ; R01 GM095384-01/GM/NIGMS NIH HHS/United States ; R01GM095384-01S1/GM/NIGMS NIH HHS/United States ; }, mesh = {Bacterial Infections/*microbiology ; *Biota ; Cystic Fibrosis/*complications ; High-Throughput Nucleotide Sequencing ; Humans ; Lung/*microbiology ; Metabolic Networks and Pathways/genetics ; Metagenome ; Sputum/microbiology ; Transcriptome ; }, abstract = {The cystic fibrosis (CF) lung contains thick mucus colonized by opportunistic pathogens which adapt to the CF lung environment over decades. The difficulty associated with sampling airways has impeded a thorough examination of the biochemical microhabitats these pathogens are exposed to. An indirect approach is to study the responses of microbial communities to these microhabitats, facilitated by high-throughput sequencing of microbial DNA and RNA from sputum samples. Microbial metagenomes and metatranscriptomes were sequenced from multiple CF patients, and the reads were assigned taxonomy and function through sequence homology to NCBI and the Kyoto Encyclopedia of Genes and Genomes (KEGG) database hierarchies. For a comparison, saliva microbial metagenomes from the Human Microbiome Project (HMP) were also analyzed. These analyses identified that functions encoded and expressed by CF microbes were significantly enriched for amino acid catabolism, folate biosynthesis, and lipoic acid biosynthesis. The data indicate that the community uses oxidative phosphorylation as a major energy source but that terminal electron acceptors were diverse. Nitrate reduction was the most abundant anaerobic respiratory pathway, and genes for nitrate reductase were largely assigned to Pseudomonas and Rothia. Although many reductive pathways of the nitrogen cycle were present, the cycle was incomplete, because the oxidative pathways were absent. Due to the abundant amino acid catabolism and incomplete nitrogen cycle, the CF microbial community appears to accumulate ammonia. This finding was verified experimentally using a CF bronchiole culture model system. The data also revealed abundant sensing and transport of iron, ammonium, zinc, and other metals along with a low-oxygen environment. This study reveals the core biochemistry and physiology of the CF microbiome. IMPORTANCE The cystic fibrosis (CF) microbial community is complex and adapts to the environmental conditions of the lung over the lifetime of a CF patient. This analysis illustrates the core functions of the CF microbial community in the context of CF lung biochemistry. There are many studies of the metabolism and physiology of individual microbes within the CF lung, but none that collectively analyze data from the whole microbiome. Understanding the core metabolism of microbes that inhabit the CF lung can provide new targets for novel therapies. The fundamental processes that CF pathogens rely on for survival may represent an Achilles heel for this pathogenic community. Novel therapies that are designed to disrupt understudied survival strategies of the CF microbial community may succeed against otherwise untreatable or antibiotic-resistant microbes.}, }
@article {pmid24637603, year = {2014}, author = {Haiser, HJ and Seim, KL and Balskus, EP and Turnbaugh, PJ}, title = {Mechanistic insight into digoxin inactivation by Eggerthella lenta augments our understanding of its pharmacokinetics.}, journal = {Gut microbes}, volume = {5}, number = {2}, pages = {233-238}, pmid = {24637603}, issn = {1949-0984}, support = {P50 GM068763/GM/NIGMS NIH HHS/United States ; P30 DK034854/DK/NIDDK NIH HHS/United States ; 2P30DK034854-26/DK/NIDDK NIH HHS/United States ; P50GM068763/GM/NIGMS NIH HHS/United States ; MFE-112991/CAPMC/CIHR/Canada ; }, mesh = {Actinobacteria/*metabolism ; Animals ; Digoxin/*metabolism/pharmacokinetics ; Gastrointestinal Tract/metabolism/*microbiology ; Germ-Free Life/physiology ; Humans ; Mice ; }, abstract = {The human gut microbiota plays a key role in pharmacology, yet the mechanisms responsible remain unclear, impeding efforts toward personalized medicine. We recently identified a cytochrome-encoding operon in the common gut Actinobacterium Eggerthella lenta that is transcriptionally activated by the cardiac drug digoxin. These genes represent a predictive microbial biomarker for the inactivation of digoxin. Gnotobiotic mouse experiments revealed that increased protein intake can limit microbial drug inactivation. Here, we present a biochemical rationale for how the proteins encoded by this operon might inactivate digoxin through substrate promiscuity. We discuss digoxin signaling in eukaryotic systems, and consider the possibility that endogenous digoxin-like molecules may have selected for microbial digoxin inactivation. Finally, we highlight the diverse contributions of gut microbes to drug metabolism, present a generalized approach to studying microbe-drug interactions, and argue that mechanistic studies will pave the way for the clinical application of this work.}, }
@article {pmid24637600, year = {2014}, author = {Levy, R and Borenstein, E}, title = {Metagenomic systems biology and metabolic modeling of the human microbiome: from species composition to community assembly rules.}, journal = {Gut microbes}, volume = {5}, number = {2}, pages = {265-270}, pmid = {24637600}, issn = {1949-0984}, support = {DP2 AT007802/AT/NCCIH NIH HHS/United States ; DP2 AT007802-01/AT/NCCIH NIH HHS/United States ; }, mesh = {Humans ; Metagenomics/*methods ; Microbiota/*genetics ; Systems Biology/*methods ; }, abstract = {The human microbiome is a key contributor to health and development. Yet little is known about the ecological forces that are at play in defining the composition of such host-associated communities. Metagenomics-based studies have uncovered clear patterns of community structure but are often incapable of distinguishing alternative structuring paradigms. In a recent study, we integrated metagenomic analysis with a systems biology approach, using a reverse ecology framework to model numerous human microbiota species and to infer metabolic interactions between species. Comparing predicted interactions with species composition data revealed that the assembly of the human microbiome is dominated at the community level by habitat filtering. Furthermore, we demonstrated that this habitat filtering cannot be accounted for by known host phenotypes or by the metabolic versatility of the various species. Here we provide a summary of our findings and offer a brief perspective on related studies and on future approaches utilizing this metagenomic systems biology framework.}, }
@article {pmid24625961, year = {2014}, author = {Meehan, CJ and Beiko, RG}, title = {A phylogenomic view of ecological specialization in the Lachnospiraceae, a family of digestive tract-associated bacteria.}, journal = {Genome biology and evolution}, volume = {6}, number = {3}, pages = {703-713}, pmid = {24625961}, issn = {1759-6653}, support = {CMF-108026//Canadian Institutes of Health Research/Canada ; }, mesh = {Animals ; Bacteria/*genetics/isolation &amp; purification ; Butyric Acid/metabolism ; Ecosystem ; Evolution, Molecular ; Gastrointestinal Tract/*microbiology ; Gene Transfer, Horizontal ; *Genome, Bacterial ; Humans ; Mammals/microbiology ; *Metagenome ; Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; }, abstract = {Several bacterial families are known to be highly abundant within the human microbiome, but their ecological roles and evolutionary histories have yet to be investigated in depth. One such family, Lachnospiraceae (phylum Firmicutes, class Clostridia) is abundant in the digestive tracts of many mammals and relatively rare elsewhere. Members of this family have been linked to obesity and protection from colon cancer in humans, mainly due to the association of many species within the group with the production of butyric acid, a substance that is important for both microbial and host epithelial cell growth. We examined the genomes of 30 Lachnospiraceae isolates to better understand the origin of butyric acid capabilities and other ecological adaptations within this group. Butyric acid production-related genes were detected in fewer than half of the examined genomes with the distribution of this function likely arising in part from lateral gene transfer (LGT). An investigation of environment-specific functional signatures indicated that human gut-associated Lachnospiraceae possess genes for endospore formation, whereas other members of this family lack key sporulation-associated genes, an observation supported by analysis of metagenomes from the human gut, oral cavity, and bovine rumen. Our analysis demonstrates that adaptation to an ecological niche and acquisition of defining functional roles within a microbiome can arise through a combination of both habitat-specific gene loss and LGT.}, }
@article {pmid24618997, year = {2014}, author = {Francis, SS and Selvin, S and Metayer, C and Wallace, AD and Crouse, V and Moore, TB and Wiemels, JL and Buffler, PA}, title = {Mode of delivery and risk of childhood leukemia.}, journal = {Cancer epidemiology, biomarkers &amp; prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology}, volume = {23}, number = {5}, pages = {876-881}, doi = {10.1158/1055-9965.EPI-13-1098}, pmid = {24618997}, issn = {1538-7755}, support = {1P01 ES018172/ES/NIEHS NIH HHS/United States ; 2R01ES009137-13/ES/NIEHS NIH HHS/United States ; }, mesh = {California ; Case-Control Studies ; Cesarean Section/*adverse effects ; Child ; Child, Preschool ; Female ; Follow-Up Studies ; Hispanic or Latino/statistics &amp; numerical data ; Humans ; Leukemia, Myeloid, Acute/ethnology/*etiology ; Male ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/ethnology/*etiology ; Prognosis ; Risk Factors ; White People/statistics &amp; numerical data ; }, abstract = {BACKGROUND: Childhood infection and immune response have long been suspected in the etiology of childhood leukemia, specifically acute lymphoblastic leukemia (ALL). Normal primary inoculation of the core human microbiome is circumvented by cesarean section (CS) delivery, which is a proposed modulator of both immune response and early-life infection.<br><br>METHODS: In this study, we examined CS delivery and the risk of childhood leukemia using data from the California Childhood Leukemia Study (CCLS) case-control study and additive logistic regression models.<br><br>RESULTS: We observed no association between CS and acute myelogenous leukemia [OR, 0.96; 95% confidence interval (CI), 0.52-1.55]. We observed a suggestive association for ALL and CS (OR, 1.22; 95% CI, 0.97-1.54). When examining common ALL (cALL), defined as ALL with expression of CD10 and CD19 surface antigens and diagnosis occurring between 2 and 5.9 years of age, we found a significant association with CS (OR, 1.44; 95% CI, 1.0-2.06). ALL subjects that are not cALL showed a similar risk as ALL overall (OR, 1.15; 95% CI, 0.91-1.44). Because of previous findings suggesting effect modification, we stratified cALL subjects by Hispanic status. Although we observed no relationship for CS in non-Hispanics (OR, 1.14; 95% CI, 0.72-1.79), we did observe a strong association between cALL and CS in Hispanics (OR, 2.34; 95% CI, 1.23-4.46).<br><br>CONCLUSION: Within the CCLS, CS delivery seems to be associated with cALL and Hispanic subjects may be driving the association.<br><br>IMPACT: Further research combined with investigations into response to early infection and the microbiome is warranted.}, }
@article {pmid24618403, year = {2014}, author = {Shafquat, A and Joice, R and Simmons, SL and Huttenhower, C}, title = {Functional and phylogenetic assembly of microbial communities in the human microbiome.}, journal = {Trends in microbiology}, volume = {22}, number = {5}, pages = {261-266}, pmid = {24618403}, issn = {1878-4380}, support = {R01 HG005969/HG/NHGRI NIH HHS/United States ; U54 DK102557/DK/NIDDK NIH HHS/United States ; R01HG005969/HG/NHGRI NIH HHS/United States ; }, mesh = {Humans ; Microbiota/*physiology ; *Phylogeny ; }, abstract = {Microbial communities associated with the human body, that is, the human microbiome, are complex ecologies critical for normal development and health. The taxonomic and phylogenetic composition of these communities tends to significantly differ among individuals, precluding the definition of a simple, shared set of 'core' microbes. Here, we review recent evidence and ecological theory supporting the assembly of host-associated microbial communities in terms of functional traits rather than specific organisms. That is, distinct microbial species may be responsible for specific host-associated functions and phenotypes in distinct hosts. We discuss how ecological processes (selective and stochastic forces) governing the assembly of metazoan communities can be adapted to describe microbial ecologies in host-associated environments, resulting in both niche-specific and 'core' metabolic and other pathways maintained throughout the human microbiome. The extent to which phylogeny and functional traits are linked in host-associated microbes, as opposed to unlinked by mechanisms, such as lateral transfer, remains to be determined. However, the definition of these functional assembly rules within microbial communities using controlled model systems and integrative 'omics' represents a fruitful opportunity for molecular systems ecology.}, }
@article {pmid24614698, year = {2014}, author = {Ardissone, AN and de la Cruz, DM and Davis-Richardson, AG and Rechcigl, KT and Li, N and Drew, JC and Murgas-Torrazza, R and Sharma, R and Hudak, ML and Triplett, EW and Neu, J}, title = {Meconium microbiome analysis identifies bacteria correlated with premature birth.}, journal = {PloS one}, volume = {9}, number = {3}, pages = {e90784}, pmid = {24614698}, issn = {1932-6203}, support = {HD059153/HD/NICHD NIH HHS/United States ; }, mesh = {Amniotic Fluid/microbiology ; Bacteria/*metabolism ; Biodiversity ; Biomarkers/metabolism ; Colony Count, Microbial ; Confounding Factors, Epidemiologic ; Delivery, Obstetric ; Female ; Gestational Age ; Humans ; Infant, Newborn ; Inflammation Mediators/metabolism ; Meconium/*microbiology ; *Microbiota ; Pregnancy ; Premature Birth/*microbiology ; S100A12 Protein/metabolism ; }, abstract = {BACKGROUND: Preterm birth is the second leading cause of death in children under the age of five years worldwide, but the etiology of many cases remains enigmatic. The dogma that the fetus resides in a sterile environment is being challenged by recent findings and the question has arisen whether microbes that colonize the fetus may be related to preterm birth. It has been posited that meconium reflects the in-utero microbial environment. In this study, correlations between fetal intestinal bacteria from meconium and gestational age were examined in order to suggest underlying mechanisms that may contribute to preterm birth.<br><br>METHODS: Meconium from 52 infants ranging in gestational age from 23 to 41 weeks was collected, the DNA extracted, and 16S rRNA analysis performed. Resulting taxa of microbes were correlated to clinical variables and also compared to previous studies of amniotic fluid and other human microbiome niches.<br><br>FINDINGS: Increased detection of bacterial 16S rRNA in meconium of infants of <33 weeks gestational age was observed. Approximately 61&#xb7;1% of reads sequenced were classified to genera that have been reported in amniotic fluid. Gestational age had the largest influence on microbial community structure (R&#x200a;=&#x200a;0&#xb7;161; p&#x200a;=&#x200a;0&#xb7;029), while mode of delivery (C-section versus vaginal delivery) had an effect as well (R&#x200a;=&#x200a;0&#xb7;100; p&#x200a;=&#x200a;0&#xb7;044). Enterobacter, Enterococcus, Lactobacillus, Photorhabdus, and Tannerella, were negatively correlated with gestational age and have been reported to incite inflammatory responses, suggesting a causative role in premature birth.<br><br>INTERPRETATION: This provides the first evidence to support the hypothesis that the fetal intestinal microbiome derived from swallowed amniotic fluid may be involved in the inflammatory response that leads to premature birth.}, }
@article {pmid24601676, year = {2014}, author = {Whelan, FJ and Verschoor, CP and Stearns, JC and Rossi, L and Luinstra, K and Loeb, M and Smieja, M and Johnstone, J and Surette, MG and Bowdish, DM}, title = {The loss of topography in the microbial communities of the upper respiratory tract in the elderly.}, journal = {Annals of the American Thoracic Society}, volume = {11}, number = {4}, pages = {513-521}, doi = {10.1513/AnnalsATS.201310-351OC}, pmid = {24601676}, issn = {2325-6621}, support = {//Canadian Institutes of Health Research/Canada ; }, mesh = {Adolescent ; Adult ; Age Factors ; Aged ; Aged, 80 and over ; DNA, Bacterial/*genetics ; Female ; Humans ; Male ; Microbiota/*genetics/immunology ; Nasal Cavity/immunology/*microbiology ; Oropharynx/immunology/*microbiology ; Polymerase Chain Reaction ; RNA, Ribosomal, 16S/*genetics ; Respiratory Tract Infections/immunology/*microbiology ; Sequence Analysis, DNA ; Streptococcus/*genetics ; Streptococcus pneumoniae/genetics ; Young Adult ; }, abstract = {RATIONALE: The microbial communities inhabiting the upper respiratory tract protect from respiratory infection. The maturity of the immune system is a major influence on the composition of the microbiome and, in youth, the microbiota and immune system are believed to mature in tandem. With age, immune function declines and susceptibility to respiratory infection increases. Whether these changes contribute to the microbial composition of the respiratory tract is unknown.<br><br>OBJECTIVES: Our goal was to determine whether the microbes of the upper respiratory tract differ between mid-aged adults (18-40 yr) and the elderly (>65 yr).<br><br>METHODS: Microbiomes of the anterior nares and oropharynx of elderly individuals were evaluated by 16S rRNA gene sequencing. These communities were compared with data on mid-aged adults obtained from the Human Microbiome Project.<br><br>MEASUREMENTS AND MAIN RESULTS: The microbiota of the elderly showed no associations with sex, comorbidities, residence, or vaccinations. Comparisons of mid-aged adults and the elderly demonstrated significant differences in the composition of the anterior nares and oropharynx, including a population in the anterior nares of the elderly that more closely resembled the oropharynx than the anterior nares of adults. The elderly oropharyngeal microbiota were characterized by increased abundance of streptococci, specifically, Streptococcus salivarius group species, but not Streptococcus pneumoniae, carriage of which was low (<3% of participants), as demonstrated by PCR (n = 4/123).<br><br>CONCLUSIONS: Microbial populations of the upper respiratory tract in mid-aged adults and the elderly differ; it is possible that these differences contribute to the increased risk of respiratory infections experienced by the elderly.}, }
@article {pmid24601662, year = {2014}, author = {Becker, J and Poroyko, V and Bhorade, S}, title = {The lung microbiome after lung transplantation.}, journal = {Expert review of respiratory medicine}, volume = {8}, number = {2}, pages = {221-231}, pmid = {24601662}, issn = {1747-6356}, support = {T32 HL007605/HL/NHLBI NIH HHS/United States ; }, mesh = {Bronchiolitis Obliterans/diagnosis/immunology/*microbiology/therapy ; Graft Rejection/diagnosis/immunology/*microbiology/therapy ; Graft Survival ; Humans ; Lung/immunology/*microbiology/*surgery ; *Lung Transplantation/adverse effects ; *Microbiota ; Risk Factors ; Time Factors ; Treatment Outcome ; }, abstract = {Lung transplantation survival remains significantly impacted by infections and the development of chronic rejection manifesting as bronchiolitis obliterans syndrome (BOS). Traditional microbiologic data has provided insight into the role of infections in BOS. Now, new non-culture-based techniques have been developed to characterize the entire population of microbes resident on the surfaces of the body, also known as the human microbiome. Early studies have identified that lung transplant patients have a different lung microbiome and have demonstrated the important finding that the transplant lung microbiome changes over time. Furthermore, both unique bacterial populations and longitudinal changes in the lung microbiome have now been suggested to play a role in the development of BOS. In the future, this technology will need to be combined with functional assays and assessment of the immune responses in the lung to help further explain the microbiome's role in the failing lung allograft.}, }
@article {pmid24599074, year = {2014}, author = {Duran-Pinedo, AE and Chen, T and Teles, R and Starr, JR and Wang, X and Krishnan, K and Frias-Lopez, J}, title = {Community-wide transcriptome of the oral microbiome in subjects with and without periodontitis.}, journal = {The ISME journal}, volume = {8}, number = {8}, pages = {1659-1672}, pmid = {24599074}, issn = {1751-7370}, support = {R01 DE021553/DE/NIDCR NIH HHS/United States ; U01 DE021127/DE/NIDCR NIH HHS/United States ; DE021553/DE/NIDCR NIH HHS/United States ; DE021127/DE/NIDCR NIH HHS/United States ; }, mesh = {Adult ; Bacteria/*genetics/isolation &amp; purification/metabolism ; Humans ; Metagenome ; Microbiota/*genetics ; Periodontitis/*microbiology ; Phylogeny ; *Transcriptome ; Virulence Factors/genetics ; }, abstract = {Despite increasing knowledge on phylogenetic composition of the human microbiome, our understanding of the in situ activities of the organisms in the community and their interactions with each other and with the environment remains limited. Characterizing gene expression profiles of the human microbiome is essential for linking the role of different members of the bacterial communities in health and disease. The oral microbiome is one of the most complex microbial communities in the human body and under certain circumstances, not completely understood, the healthy microbial community undergoes a transformation toward a pathogenic state that gives rise to periodontitis, a polymicrobial inflammatory disease. We report here the in situ genome-wide transcriptome of the subgingival microbiome in six periodontally healthy individuals and seven individuals with periodontitis. The overall picture of metabolic activities showed that iron acquisition, lipopolysaccharide synthesis and flagellar synthesis were major activities defining disease. Unexpectedly, the vast majority of virulence factors upregulated in subjects with periodontitis came from organisms that are not considered major periodontal pathogens. One of the organisms whose gene expression profile was characterized was the uncultured candidate division TM7, showing an upregulation of putative virulence factors in the diseased community. These data enhance understanding of the core activities that are characteristic of periodontal disease as well as the role that individual organisms in the subgingival community play in periodontitis.}, }
@article {pmid24595026, year = {2014}, author = {Tu, Q and He, Z and Li, Y and Chen, Y and Deng, Y and Lin, L and Hemme, CL and Yuan, T and Van Nostrand, JD and Wu, L and Zhou, X and Shi, W and Li, L and Xu, J and Zhou, J}, title = {Development of HuMiChip for functional profiling of human microbiomes.}, journal = {PloS one}, volume = {9}, number = {3}, pages = {e90546}, pmid = {24595026}, issn = {1932-6203}, mesh = {Gastrointestinal Tract/*microbiology ; High-Throughput Nucleotide Sequencing/instrumentation ; Humans ; Metagenome ; *Microbiota ; Mouth/*microbiology ; Oligonucleotide Array Sequence Analysis/*instrumentation ; }, abstract = {Understanding the diversity, composition, structure, function, and dynamics of human microbiomes in individual human hosts is crucial to reveal human-microbial interactions, especially for patients with microbially mediated disorders, but challenging due to the high diversity of the human microbiome. Here we have developed a functional gene-based microarray for profiling human microbiomes (HuMiChip) with 36,802 probes targeting 50,007 protein coding sequences for 139 key functional gene families. Computational evaluation suggested all probes included are highly specific to their target sequences. HuMiChip was used to analyze human oral and gut microbiomes, showing significantly different functional gene profiles between oral and gut microbiome. Obvious shifts of microbial functional structure and composition were observed for both patients with dental caries and periodontitis from moderate to advanced stages, suggesting a progressive change of microbial communities in response to the diseases. Consistent gene family profiles were observed by both HuMiChip and next generation sequencing technologies. Additionally, HuMiChip was able to detect gene families at as low as 0.001% relative abundance. The results indicate that the developed HuMiChip is a useful and effective tool for functional profiling of human microbiomes.}, }
@article {pmid24591822, year = {2014}, author = {Sze, MA and Hogg, JC and Sin, DD}, title = {Bacterial microbiome of lungs in COPD.}, journal = {International journal of chronic obstructive pulmonary disease}, volume = {9}, number = {}, pages = {229-238}, pmid = {24591822}, issn = {1178-2005}, mesh = {Anti-Bacterial Agents/therapeutic use ; Disease Progression ; Gastrointestinal Tract/microbiology ; Humans ; Lung/drug effects/immunology/*microbiology/physiopathology ; *Microbiota ; Pulmonary Disease, Chronic Obstructive/drug therapy/epidemiology/immunology/*microbiology/physiopathology ; Risk Factors ; Smoking/adverse effects/epidemiology ; }, abstract = {Chronic obstructive pulmonary disease (COPD) is currently the third leading cause of death in the world. Although smoking is the main risk factor for this disease, only a minority of smokers develop COPD. Why this happens is largely unknown. Recent discoveries by the human microbiome project have shed new light on the importance and richness of the bacterial microbiota at different body sites in human beings. The microbiota plays a particularly important role in the development and functional integrity of the immune system. Shifts or perturbations in the microbiota can lead to disease. COPD is in part mediated by dysregulated immune responses to cigarette smoke and other environmental insults. Although traditionally the lung has been viewed as a sterile organ, by using highly sensitive genomic techniques, recent reports have identified diverse bacterial communities in the human lung that may change in COPD. This review summarizes the current knowledge concerning the lung microbiota in COPD and its potential implications for pathogenesis of the disease.}, }
@article {pmid24588058, year = {2014}, author = {Cazer, CL and Volkova, VV and Gröhn, YT}, title = {Use of pharmacokinetic modeling to assess antimicrobial pressure on enteric bacteria of beef cattle fed chlortetracycline for growth promotion, disease control, or treatment.}, journal = {Foodborne pathogens and disease}, volume = {11}, number = {5}, pages = {403-411}, doi = {10.1089/fpd.2013.1677}, pmid = {24588058}, issn = {1556-7125}, mesh = {Animal Feed/analysis ; Animals ; Anti-Bacterial Agents/administration &amp; dosage/*pharmacokinetics ; Cattle/growth &amp; development ; Chlortetracycline/administration &amp; dosage/*pharmacokinetics ; Diet/veterinary ; Enterobacteriaceae/*drug effects/isolation &amp; purification ; Feces/chemistry ; Gastric Mucosa/metabolism ; Intestinal Mucosa/metabolism ; Male ; Meat/*microbiology ; Models, Theoretical ; }, abstract = {Antimicrobial use in food animals may increase antimicrobial resistance in their enteric bacteria that can be transferred to human microbiome. Over 70% of U.S. beef feedlots use non-ionophore in-feed antimicrobials for animal disease control, treatment, or growth promotion. The fraction of feedlots feeding chlortetracycline (CTC), mostly for disease control but also for treatment, has increased since the mid-1990s to present. Quantitative information on the antimicrobial selective pressure on the enteric bacteria of cattle fed CTC is lacking. Hence, the purpose of this study was to develop a deterministic mathematical model of the pharmacokinetics of ingested CTC in a beef steer and estimate the concentration of antimicrobially active (undegraded) CTC in the animal's large intestine. To evaluate the fit of the model to existing data, we also estimated the CTC concentrations in the central circulation, and fresh and aging manure from the steer. The model accounted for CTC abiotic degradation while in the gastrointestinal tract, absorption into the central circulation and tissues, biliary and renal excretion, and removal from the intestine by defecation. The model included an increase in the large intestine volume as the steer grew. We estimated that during CTC feeding to a 300-kg steer for growth promotion, the maximal drug concentration in the large intestine was 0.3 μg/mL; during disease control it was 1.7 μg/mL; and during treatment it was 31.5 μg/mL. The estimated CTC concentrations in the central circulation and the steer's manure agreed reasonably well with published data.}, }
@article {pmid24564823, year = {2014}, author = {Stephenson, RE and Gutierrez, D and Peters, C and Nichols, M and Boles, BR}, title = {Elucidation of bacteria found in car interiors and strategies to reduce the presence of potential pathogens.}, journal = {Biofouling}, volume = {30}, number = {3}, pages = {337-346}, pmid = {24564823}, issn = {1029-2454}, support = {R01 AI099065/AI/NIAID NIH HHS/United States ; }, mesh = {Anti-Infective Agents/*pharmacology ; *Automobiles ; Biofouling/*prevention &amp; control ; Colony Count, Microbial ; Environmental Exposure/analysis ; *Microbiota ; Silver/*pharmacology ; Surface Properties ; }, abstract = {The human microbiome is influenced by a number of factors, including environmental exposure to microbes. Because many humans spend a large amount of time in built environments, it can be expected that the microbial ecology of these environments will influence the human microbiome. In an attempt to further understand the microbial ecology of built environments, the microbiota of car interiors was analyzed using culture dependent and culture independent methods. While it was found that the number and type of bacteria varied widely among the cars and sites tested, Staphylococcus and Propionibacterium were nearly always the dominant genera found at the locations sampled. Because Staphylococcus is of particular concern to human health, the characteristics of this genus found in car interiors were investigated. Staphylococcus epidermidis, S. aureus, and S. warnerii were the most prevalent staphylococcal species found, and 22.6% of S. aureus strains isolated from shared community vehicles were resistant to methicillin. The reduction in the prevalence of pathogenic bacteria in cars by using silver-based antimicrobial surface coatings was also evaluated. Coatings containing 5% silver ion additives were applied to steering wheels, placed in cars for five months and were found to eliminate the presence of culturable pathogenic bacteria recovered from these sites relative to controls. Together, these results provide new insight into the microbiota found in an important built environment, the automobile, and potential strategies for controlling the presence of human pathogens.}, }
@article {pmid24555915, year = {2014}, author = {Riccitelli, NJ and Delwart, E and Lupták, A}, title = {Identification of minimal HDV-like ribozymes with unique divalent metal ion dependence in the human microbiome.}, journal = {Biochemistry}, volume = {53}, number = {10}, pages = {1616-1626}, doi = {10.1021/bi401717w}, pmid = {24555915}, issn = {1520-4995}, mesh = {Bacteria/chemistry/genetics/*metabolism ; Binding Sites ; Calcium/*metabolism ; Catalysis ; Cations, Divalent/*chemistry ; Humans ; Kinetics ; Magnesium/*metabolism ; *Microbiota ; Nucleic Acid Conformation ; RNA, Bacterial/chemistry/genetics/*metabolism ; RNA, Catalytic/chemistry/genetics/*metabolism ; }, abstract = {HDV-like self-cleaving ribozymes have been found in a wide variety of organisms, implicated in diverse biological processes, and their activity typically shows a strong divalent metal dependence, but little metal specificity. Recent studies suggested that very short variants of these ribozymes exist in nature, but their distribution and biochemical properties have not been established. To map out the distribution of small HDV-like ribozymes, the drz-Spur-3 sequence was minimized to yield a core construct for structure-based bioinformatic searches. These searches revealed several microbial ribozymes, particularly in the human microbiome. Kinetic profile of the smallest ribozyme revealed two distinct metal binding sites, only one of which promotes fast catalysis. Furthermore, this ribozyme showed markedly reduced activity in Ca(2+), even in the presence of physiological Mg(2+) concentrations. Our study substantially expands the number of microbial HDV-like ribozymes and provides an example of cleavage regulation by divalent metals.}, }
@article {pmid24533884, year = {2014}, author = {Bisgaard, H and Bønnelykke, K and Stokholm, J}, title = {Immune-mediated diseases and microbial exposure in early life.}, journal = {Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology}, volume = {44}, number = {4}, pages = {475-481}, doi = {10.1111/cea.12291}, pmid = {24533884}, issn = {1365-2222}, mesh = {Age Factors ; *Host-Pathogen Interactions ; Humans ; Immune System Diseases/*etiology/microbiology/virology ; }, abstract = {The non-communicable disease pandemic includes immune-mediated diseases such as asthma and allergy, which are likely originating in early life where the immature immune system is prone to alterations caused by the exposome. The timing of exposure seems critical for the developing immune system, and certain exposures may have detrimental effects in the earliest life, but no or even beneficial effects later. The human microbiome and infections are candidates as intermediary in the interaction between the host and the environment. The evidence seems inconsistent as infections as well as particular colonization patterns in neonates drive both short-term and long-term asthma symptoms, while, on the other hand, the composition of the microbiome in early life may protect against asthma and allergy in later life. This apparent contradiction may be explained by a deeper disease heterogeneity than we are currently able to discriminate, and in particular, the indiscriminate lumping together of different diseases into one atopic disease category. Also, the microbiome needs a differentiated understanding, considering balance between microbial groups, diversity and microbial genetic capability. Furthermore, the effects of the microbial exposure may only affect individuals with certain susceptibility genes. Few of the observations have been replicated, and publication bias is likely. Therefore, we are still far from understanding, or having proved, causal effects of the human microbiome. Still, the microbiome-gene interaction is a fascinating paradigm that fosters exiting research and promises a breakthrough in the understanding of the mechanisms driving asthma, allergy and eczema, and potentially also other immune-mediated non-communicable diseases.}, }
@article {pmid24528498, year = {2014}, author = {Fishman, JA}, title = {From the classic concepts to modern practice.}, journal = {Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases}, volume = {20 Suppl 7}, number = {}, pages = {4-9}, doi = {10.1111/1469-0691.12593}, pmid = {24528498}, issn = {1469-0691}, mesh = {Humans ; Immunocompromised Host ; Immunosuppressive Agents/therapeutic use ; Incidence ; Infection Control/*methods ; Opportunistic Infections/diagnosis/*epidemiology/*prevention &amp; control/therapy ; *Organ Transplantation ; Prevalence ; *Transplant Recipients ; }, abstract = {Transplant infectious disease is a field in evolution. For most allograft recipients, immunosuppressive therapies are more potent and have reduced the incidence of acute allograft rejection. At the same time, these therapies have increased susceptibility to many opportunistic infections and virally-mediated malignancies. Immunological tolerance has been achieved in only small numbers of patients who avoid drug toxicities and infection for as long as tolerance persists. The traditional timeline of post-transplant infections remains useful in the development of a differential diagnosis for patients with infectious syndromes. However, patterns of infection in the post-transplant period have changed over the past decade. Recipients are derived from a broader range of socioeconomic and geographical backgrounds. Infections are diagnosed more often, with improved microbiological assays (e.g. nucleic acid testing, NAT) used routinely in the diagnosis and management of common infections and increasingly in the screening of organ donors. Patterns of opportunistic infection have been altered by the increased identification of organisms demonstrating antimicrobial resistance and by the broader use of strategies to prevent viral, bacterial and fungal (including Pneumocystis) infections. Newer techniques are being applied (e.g. HLA-linked tetramer binding, intracellular cytokine staining) to assess pathogen-specific immunity. These are being integrated into clinical practice to assess individual susceptibility to specific infections. Infection, inflammation and the human microbiome are recognized as playing a central role in shaping innate and adaptive immune responses, graft rejection and autoimmunity. The full impact of infection on transplantation is only beginning to be appreciated.}, }
@article {pmid24522917, year = {2014}, author = {Ma, Y and Madupu, R and Karaoz, U and Nossa, CW and Yang, L and Yooseph, S and Yachimski, PS and Brodie, EL and Nelson, KE and Pei, Z}, title = {Human papillomavirus community in healthy persons, defined by metagenomics analysis of human microbiome project shotgun sequencing data sets.}, journal = {Journal of virology}, volume = {88}, number = {9}, pages = {4786-4797}, pmid = {24522917}, issn = {1098-5514}, support = {UH3 CA140233/CA/NCI NIH HHS/United States ; U01 CA182370/CA/NCI NIH HHS/United States ; UH3CA140233/CA/NCI NIH HHS/United States ; R01 CA159036/CA/NCI NIH HHS/United States ; U01CA18237/CA/NCI NIH HHS/United States ; }, mesh = {Coinfection/epidemiology/virology ; Female ; *Healthy Volunteers ; Humans ; Metagenomics ; *Microbiota ; Papillomaviridae/*classification/genetics/*isolation &amp; purification ; Papillomavirus Infections/epidemiology/*virology ; Prevalence ; Sequence Analysis, DNA ; }, abstract = {UNLABELLED: Human papillomavirus (HPV) causes a number of neoplastic diseases in humans. Here, we show a complex normal HPV community in a cohort of 103 healthy human subjects, by metagenomics analysis of the shotgun sequencing data generated from the NIH Human Microbiome Project. The overall HPV prevalence was 68.9% and was highest in the skin (61.3%), followed by the vagina (41.5%), mouth (30%), and gut (17.3%). Of the 109 HPV types as well as additional unclassified types detected, most were undetectable by the widely used commercial kits targeting the vaginal/cervical HPV types. These HPVs likely represent true HPV infections rather than transitory exposure because of strong organ tropism and persistence of the same HPV types in repeat samples. Coexistence of multiple HPV types was found in 48.1% of the HPV-positive samples. Networking between HPV types, cooccurrence or exclusion, was detected in vaginal and skin samples. Large contigs assembled from short HPV reads were obtained from several samples, confirming their genuine HPV origin. This first large-scale survey of HPV using a shotgun sequencing approach yielded a comprehensive map of HPV infections among different body sites of healthy human subjects.<br><br>IMPORTANCE: This nonbiased survey indicates that the HPV community in healthy humans is much more complex than previously defined by widely used kits that are target selective for only a few high- and low-risk HPV types for cervical cancer. The importance of nononcogenic viruses in a mixed HPV infection could be for stimulating or inhibiting a coexisting oncogenic virus via viral interference or immune cross-reaction. Knowledge gained from this study will be helpful to guide the designing of epidemiological and clinical studies in the future to determine the impact of nononcogenic HPV types on the outcome of HPV infections.}, }
@article {pmid24512934, year = {2014}, author = {Holman, DM and Grossman, M and Henley, SJ and Peipins, LA and Tison, L and White, MC}, title = {Opportunities for cancer prevention during midlife: highlights from a meeting of experts.}, journal = {American journal of preventive medicine}, volume = {46}, number = {3 Suppl 1}, pages = {S73-80}, pmid = {24512934}, issn = {1873-2607}, support = {CC999999//Intramural CDC HHS/United States ; }, mesh = {Congresses as Topic ; Health Policy ; Health Promotion/methods ; Health Status Disparities ; Humans ; Middle Aged ; Neoplasms/*prevention &amp; control ; Preventive Medicine/*methods ; Risk Factors ; }, abstract = {This paper provides highlights from a CDC-hosted meeting on opportunities for cancer prevention during midlife (roughly ages 45-64 years). Positive changes during this phase of life have the potential to prevent cancer incidence later in life, making this phase an opportune time for targeted prevention efforts to facilitate healthy aging and increased longevity. Risk and protective factors discussed during the meeting included exposure to radiation from medical imaging procedures, circadian disruption, chemical exposures, dietary factors, alcohol consumption, obesity, physical activity, diabetes, and the human microbiome. Although many of these factors are well recognized as being related to cancer incidence, others are not as widely recognized or have emerged as growing areas of research. Meeting participants discussed promising strategies for cancer prevention targeting this age group. Just as there are multiple determinants of cancer risk, there are likely multiple solutions. Changes to social and physical environments may facilitate healthy behaviors and minimize harmful exposures. Information shared during the meeting about health disparities in the U.S. highlighted the need to go beyond traditional approaches to cancer prevention to truly reach vulnerable populations. Partnerships are also a key component to prevention efforts; community-based and nonprofit organizations, the healthcare system, research institutions, state health departments, and federal agencies were all noted as important partners in prevention efforts. Coordinated, multi-disciplinary efforts across multiple chronic diseases may provide opportunities for synergistic effects. Further, leveraging key partnerships and existing communication channels can maximize success and facilitate timely translation of research findings into public health practice.}, }
@article {pmid24502797, year = {2014}, author = {Tuzhikov, A and Panchin, A and Shestopalov, VI}, title = {TUIT, a BLAST-based tool for taxonomic classification of nucleotide sequences.}, journal = {BioTechniques}, volume = {56}, number = {2}, pages = {78-84}, pmid = {24502797}, issn = {1940-9818}, support = {R01 EY022038/EY/NEI NIH HHS/United States ; EY02238/EY/NEI NIH HHS/United States ; }, mesh = {Algorithms ; Cells, Cultured ; *DNA/classification/genetics ; *Databases, Genetic ; Humans ; RNA, Ribosomal, 16S/*genetics ; Sequence Analysis, DNA/*methods ; }, abstract = {Pyrosequencing of 16S ribosomal RNA (rRNA) genes has become the gold standard in human microbiome studies. The routine task of taxonomic classification using 16S rRNA reads is commonly performed by the Ribosomal Database Project (RDP) II Classifier, a robust tool that relies on a set of well-characterized reference sequences. However, the RDP II Classifier may be unable to classify a significant part of the data set due to the absence of proper reference sequences. The taxonomic classification for some unclassified sequences might still be performed using BLAST searches against large and frequently updated nucleotide databases. Here we introduce TUIT (Taxonomic Unit Identification Tool)-an efficient open source and platform-independent application that can perform taxonomic classification on its own or can be used in combination with the RDP II Classifier to maximize the taxonomic identification rate. Using a set of simulated DNA sequences, we demonstrate that the algorithm performs taxonomic classification with high specificity for sequences as short as 125 base pairs. TUIT is applicable for 16S rRNA gene sequence classification; however, it is not restricted to 16S rRNA sequences. In addition, TUIT may be used as a complementary tool for effective taxonomic classification of nucleotide sequences generated by many current platforms, such as Roche 454 and Illumina. Stand-alone TUIT is available online at http://sourceforge.net/projects/tuit/.}, }
@article {pmid24499669, year = {2014}, author = {Kim, S and Kim, JH and Park, BO and Kwak, YS}, title = {Perspectives on the therapeutic potential of short-chain fatty acid receptors.}, journal = {BMB reports}, volume = {47}, number = {3}, pages = {173-178}, pmid = {24499669}, issn = {1976-670X}, mesh = {Animals ; Fatty Acids, Volatile/*metabolism ; Humans ; Molecular Targeted Therapy ; Receptors, G-Protein-Coupled/agonists/antagonists &amp; inhibitors/metabolism/*therapeutic use ; }, abstract = {There is rapidly growing interest in the human microbiome because of its implication in metabolic disorders and inflammatory diseases. Consequently, understanding the biology of short chain fatty acids and their receptors has become very important for identifying novel therapeutic avenues. GPR41 and GPR43 have been recognized as the cognate receptors for SCFAs and their roles in metabolism and inflammation have drawn much attention in recent years. GPR43 is highly expressed on immune cells and has been suggested to play a role in inflammatory diseases such as inflammatory bowel disease. Both GPR41 and GPR43 have been implicated in diabetes and obesity via the regulation of adipose tissue and gastrointestinal hormones. So far, many studies have provided contradictory results, and therefore further research is required to validate these receptors as drug targets. We will also discuss the synthetic modulators of GPR41 and GPR43 that are critical to understanding the functions of these receptors.}, }
@article {pmid24488273, year = {2014}, author = {Hemarajata, P and Spinler, JK and Balderas, MA and Versalovic, J}, title = {Identification of a proton-chloride antiporter (EriC) by Himar1 transposon mutagenesis in Lactobacillus reuteri and its role in histamine production.}, journal = {Antonie van Leeuwenhoek}, volume = {105}, number = {3}, pages = {579-592}, pmid = {24488273}, issn = {1572-9699}, support = {U01 CA170930/CA/NCI NIH HHS/United States ; UH3 DK083990/DK/NIDDK NIH HHS/United States ; R01 DK065075/DK/NIDDK NIH HHS/United States ; P30 DK056338/DK/NIDDK NIH HHS/United States ; DK56338/DK/NIDDK NIH HHS/United States ; R01 AT004326/AT/NCCIH NIH HHS/United States ; }, mesh = {Antiporters/*genetics/*metabolism ; Biological Transport ; Chlorides/metabolism ; *DNA Transposable Elements ; Gene Expression ; Gene Expression Regulation, Bacterial ; Gene Order ; Gene Silencing ; Genetic Vectors/genetics ; Histamine/*biosynthesis ; Histidine Decarboxylase/genetics ; Limosilactobacillus reuteri/drug effects/*genetics/*metabolism ; Multigene Family ; *Mutagenesis ; Mutagenesis, Insertional ; Probiotics ; Promoter Regions, Genetic ; Protons ; Tumor Necrosis Factors/pharmacology ; }, abstract = {The gut microbiome may modulate intestinal immunity by luminal conversion of dietary amino acids to biologically active signals. The model probiotic organism Lactobacillus reuteri ATCC PTA 6475 is indigenous to the human microbiome, and converts the amino acid L-histidine to the biogenic amine, histamine. Histamine suppresses tumor necrosis factor (TNF) production by human myeloid cells and is a product of L-histidine decarboxylation, which is a proton-facilitated reaction. A transposon mutagenesis strategy was developed based on a single-plasmid nisin-inducible Himar1 transposase/transposon delivery system for L. reuteri. A highly conserved proton-chloride antiporter gene (eriC), a gene widely present in the gut microbiome was discovered by Himar1 transposon (Tn)-mutagenesis presented in this study. Genetic inactivation of eriC by transposon insertion and genetic recombineering resulted in reduced ability of L. reuteri to inhibit TNF production by activated human myeloid cells, diminished histamine production by the bacteria and downregulated expression of histidine decarboxylase cluster genes compared to those of WT 6475. EriC belongs to a large family of ion transporters that includes chloride channels and proton-chloride antiporters and may facilitate the availability of protons for the decarboxylation reaction, resulting in histamine production by L. reuteri. This report leverages the tools of bacterial genetics for probiotic gene discovery. The findings highlight the widely conserved nature of ion transporters in bacteria and how ion transporters are coupled with amino acid decarboxylation and contribute to microbiome-mediated immunomodulation.}, }
@article {pmid24487378, year = {2014}, author = {Krom, BP and Kidwai, S and Ten Cate, JM}, title = {Candida and other fungal species: forgotten players of healthy oral microbiota.}, journal = {Journal of dental research}, volume = {93}, number = {5}, pages = {445-451}, doi = {10.1177/0022034514521814}, pmid = {24487378}, issn = {1544-0591}, mesh = {Bacterial Adhesion/physiology ; Biofilms ; Candida/*physiology ; Ecosystem ; Fungi/*physiology ; Humans ; Microbial Consortia/physiology ; Microbial Interactions/physiology ; Mouth/*microbiology ; Oral Health ; }, abstract = {In the last half-decade or so, interest in the bacterial part of the human microbiome and its role in maintaining health have received considerable attention. Since 2009, over 300 publications have appeared describing the oral bacterial microbiome. Strikingly, fungi in the oral cavity have been studied exclusively in relation to pathologies. However, little to nothing is known about a role of fungi in establishing and maintaining a healthy oral ecology. In a healthy ecology, balance is maintained by the combined positive and negative influences between and among its members. Interactions between fungi and bacteria occur primarily at a physical and chemical level. Physical interactions are represented by (co-)adhesion and repulsion (exclusion), while chemical interactions include metabolic dependencies, quorum-sensing, and the production of antimicrobial agents. Information obtained from oral model systems and also from studies on the role of fungi in gastro-intestinal ecology indicates that fungi influence bacterial behavior through these different interactions. This review describes our current knowledge of the interactions between fungi and bacteria and aims to illustrate that further research is required to establish the role of fungi in maintaining a healthy oral cavity.}, }
@article {pmid24486053, year = {2014}, author = {Morgan, XC and Huttenhower, C}, title = {Meta'omic analytic techniques for studying the intestinal microbiome.}, journal = {Gastroenterology}, volume = {146}, number = {6}, pages = {1437-1448.e1}, doi = {10.1053/j.gastro.2014.01.049}, pmid = {24486053}, issn = {1528-0012}, support = {R01HG005969/HG/NHGRI NIH HHS/United States ; }, mesh = {Animals ; Bacteria/classification/*genetics ; DNA, Bacterial/analysis ; Gene Expression Profiling ; Gene Expression Regulation, Bacterial ; Genotype ; High-Throughput Nucleotide Sequencing ; Host-Pathogen Interactions ; Humans ; Inflammatory Bowel Diseases/microbiology ; Intestines/*microbiology ; *Metagenome ; *Metagenomics/methods ; Microbiota/*genetics ; Models, Statistical ; Phenotype ; Phylogeny ; RNA, Bacterial/analysis ; RNA, Ribosomal, 16S/analysis ; Ribotyping ; Transcriptome ; }, abstract = {Nucleotide sequencing has become increasingly common and affordable, and is now a vital tool for studies of the human microbiome. Comprehensive microbial community surveys such as MetaHit and the Human Microbiome Project have described the composition and molecular functional profile of the healthy (normal) intestinal microbiome. This knowledge will increase our ability to analyze host and microbial DNA (genome) and RNA (transcriptome) sequences. Bioinformatic and statistical tools then can be used to identify dysbioses that might cause disease, and potential treatments. Analyses that identify perturbations in specific molecules can leverage thousands of culture-based isolate genomes to contextualize culture-independent sequences, or may integrate sequence data with whole-community functional assays such as metaproteomic or metabolomic analyses. We review the state of available systems-level models for studies of the intestinal microbiome, along with analytic techniques and tools that can be used to determine its functional capabilities in healthy and unhealthy individuals.}, }
@article {pmid24484530, year = {2014}, author = {Vaz-Moreira, I and Nunes, OC and Manaia, CM}, title = {Bacterial diversity and antibiotic resistance in water habitats: searching the links with the human microbiome.}, journal = {FEMS microbiology reviews}, volume = {38}, number = {4}, pages = {761-778}, doi = {10.1111/1574-6976.12062}, pmid = {24484530}, issn = {1574-6976}, mesh = {*Bacterial Physiological Phenomena ; *Biodiversity ; *Drug Resistance, Bacterial ; *Drug Resistance, Microbial ; *Ecosystem ; Humans ; *Water Microbiology ; }, abstract = {Water is one of the most important bacterial habitats on Earth. As such, water represents also a major way of dissemination of bacteria between different environmental compartments. Human activities led to the creation of the so-called urban water cycle, comprising different sectors (waste, surface, drinking water), among which bacteria can hypothetically be exchanged. Therefore, bacteria can be mobilized between unclean water habitats (e.g. wastewater) and clean or pristine water environments (e.g. disinfected and spring drinking water) and eventually reach humans. In addition, bacteria can also transfer mobile genetic elements between different water types, other environments (e.g. soil) and humans. These processes may involve antibiotic resistant bacteria and antibiotic resistance genes. In this review, the hypothesis that some bacteria may share different water compartments and be also hosted by humans is discussed based on the comparison of the bacterial diversity in different types of water and with the human-associated microbiome. The role of such bacteria as potential disseminators of antibiotic resistance and the inference that currently only a small fraction of the clinically relevant antibiotic resistome may be known is discussed.}, }
@article {pmid24479734, year = {2014}, author = {Jones, ML and Martoni, CJ and Ganopolsky, JG and Labbé, A and Prakash, S}, title = {The human microbiome and bile acid metabolism: dysbiosis, dysmetabolism, disease and intervention.}, journal = {Expert opinion on biological therapy}, volume = {14}, number = {4}, pages = {467-482}, doi = {10.1517/14712598.2014.880420}, pmid = {24479734}, issn = {1744-7682}, mesh = {Animals ; Atherosclerosis/metabolism ; Bile Acids and Salts/*metabolism ; Diabetes Mellitus, Type 2/metabolism ; Dysbiosis/*metabolism ; Female ; Gastrointestinal Diseases/metabolism ; Health Status ; Humans ; Male ; Metabolic Diseases/*metabolism ; Microbiota/*physiology ; Obesity/metabolism/microbiology ; Osteoporosis/metabolism ; Probiotics ; }, abstract = {INTRODUCTION: Recent evidence indicates that the human gut microbiome plays a significant role in health and disease. Dysbiosis, defined as a pathological imbalance in a microbial community, is becoming increasingly appreciated as a 'central environmental factor' that is both associated with complex phenotypes and affected by host genetics, diet and antibiotic use. More recently, a link has been established between the dysmetabolism of bile acids (BAs) in the gut to dysbiosis.<br><br>AREAS COVERED: BAs, which are transformed by the gut microbiota, have been shown to regulate intestinal homeostasis and are recognized as signaling molecules in a wide range of metabolic processes. This review will examine the connection between BA metabolism as it relates to the gut microbiome and its implication in health and disease.<br><br>EXPERT OPINION: A disrupted gut microbiome, including a reduction of bile salt hydrolase (BSH)-active bacteria, can significantly impair the metabolism of BAs and may result in an inability to maintain glucose homeostasis as well as normal cholesterol breakdown and excretion. To better understand the link between dysbiosis, BA dysmetabolism and chronic degenerative disease, large-scale metagenomic sequencing studies, metatranscriptomics, metaproteomics and metabolomics should continue to catalog functional diversity in the gastrointestinal tract of both healthy and diseased populations. Further, BSH-active probiotics should continue to be explored as treatment options to help restore metabolic levels.}, }
@article {pmid24473987, year = {2014}, author = {Eliaz, I}, title = {Human microbiome and nutrition: untapped clinical potential awaits.}, journal = {Alternative therapies in health and medicine}, volume = {20 Suppl 1}, number = {}, pages = {58-60}, pmid = {24473987}, issn = {1078-6791}, mesh = {Complementary Therapies ; Humans ; *Microbiota ; *Nutritional Physiological Phenomena ; }, }
@article {pmid24466089, year = {2014}, author = {Card, RM and Warburton, PJ and MacLaren, N and Mullany, P and Allan, E and Anjum, MF}, title = {Application of microarray and functional-based screening methods for the detection of antimicrobial resistance genes in the microbiomes of healthy humans.}, journal = {PloS one}, volume = {9}, number = {1}, pages = {e86428}, pmid = {24466089}, issn = {1932-6203}, mesh = {Amino Acid Sequence ; Anti-Infective Agents/pharmacology ; Dihydropteroate Synthase/chemistry/genetics ; Drug Resistance, Microbial/*genetics ; Feces/microbiology ; Healthy Volunteers ; Humans ; *Metagenome ; Microarray Analysis/methods ; Microbial Sensitivity Tests ; *Microbiota ; Molecular Sequence Data ; Saliva/microbiology ; Sequence Alignment ; }, abstract = {The aim of this study was to screen for the presence of antimicrobial resistance genes within the saliva and faecal microbiomes of healthy adult human volunteers from five European countries. Two non-culture based approaches were employed to obviate potential bias associated with difficult to culture members of the microbiota. In a gene target-based approach, a microarray was employed to screen for the presence of over 70 clinically important resistance genes in the saliva and faecal microbiomes. A total of 14 different resistance genes were detected encoding resistances to six antibiotic classes (aminoglycosides, β-lactams, macrolides, sulphonamides, tetracyclines and trimethoprim). The most commonly detected genes were erm(B), blaTEM, and sul2. In a functional-based approach, DNA prepared from pooled saliva samples was cloned into Escherichia coli and screened for expression of resistance to ampicillin or sulphonamide, two of the most common resistances found by array. The functional ampicillin resistance screen recovered genes encoding components of a predicted AcrRAB efflux pump. In the functional sulphonamide resistance screen, folP genes were recovered encoding mutant dihydropteroate synthase, the target of sulphonamide action. The genes recovered from the functional screens were from the chromosomes of commensal species that are opportunistically pathogenic and capable of exchanging DNA with related pathogenic species. Genes identified by microarray were not recovered in the activity-based screen, indicating that these two methods can be complementary in facilitating the identification of a range of resistance mechanisms present within the human microbiome. It also provides further evidence of the diverse reservoir of resistance mechanisms present in bacterial populations in the human gut and saliva. In future the methods described in this study can be used to monitor changes in the resistome in response to antibiotic therapy.}, }
@article {pmid24460444, year = {2014}, author = {Segal, LN and Rom, WN and Weiden, MD}, title = {Lung microbiome for clinicians. New discoveries about bugs in healthy and diseased lungs.}, journal = {Annals of the American Thoracic Society}, volume = {11}, number = {1}, pages = {108-116}, pmid = {24460444}, issn = {2325-6621}, support = {K24 AI080298/AI/NIAID NIH HHS/United States ; K23 AI102970/AI/NIAID NIH HHS/United States ; K24 AI080298A/AI/NIAID NIH HHS/United States ; 5 U01CA086137-14/CA/NCI NIH HHS/United States ; UL1 TR000038/TR/NCATS NIH HHS/United States ; U01 CA086137/CA/NCI NIH HHS/United States ; }, mesh = {Humans ; Inflammation ; Lung/immunology/*microbiology ; Lung Diseases/immunology/*microbiology ; Metagenome ; *Microbiota ; }, abstract = {Microbes are readily cultured from epithelial surfaces of the skin, mouth, and colon. In the last 10 years, culture-independent DNA-based techniques demonstrated that much more complex microbial communities reside on most epithelial surfaces; this includes the lower airways, where bacterial culture had failed to reliably demonstrate resident bacteria. Exposure to a diverse bacterial environment is important for adequate immunological development. The most common microbes found in the lower airways are also found in the upper airways. Increasing abundance of oral characteristic taxa is associated with increased inflammatory cells and exhaled nitric oxide, suggesting that the airway microbiome induces an immunological response in the lung. Furthermore, rhinovirus infection leads to outgrowth of Haemophilus in patients with chronic obstructive pulmonary disease, and human immunodeficiency virus-infected subjects have more Tropheryma whipplei in the lower airway, suggesting a bidirectional interaction in which the host immune defenses also influence the microbial niche. Quantitative and/or qualitative changes in the lung microbiome may be relevant for disease progression and exacerbations in a number of pulmonary diseases. Future investigations with longitudinal follow-up to understand the dynamics of the lung microbiome may lead to the development of new therapeutic targets.}, }
@article {pmid24454771, year = {2014}, author = {Xie, G and Lo, CC and Scholz, M and Chain, PS}, title = {Recruiting human microbiome shotgun data to site-specific reference genomes.}, journal = {PloS one}, volume = {9}, number = {1}, pages = {e84963}, pmid = {24454771}, issn = {1932-6203}, support = {Y01 DE006006/DE/NIDCR NIH HHS/United States ; Y1-DE-6006-02/DE/NIDCR NIH HHS/United States ; }, mesh = {Humans ; *Metagenome ; *Microbiota ; }, abstract = {The human body consists of innumerable multifaceted environments that predispose colonization by a number of distinct microbial communities, which play fundamental roles in human health and disease. In addition to community surveys and shotgun metagenomes that seek to explore the composition and diversity of these microbiomes, there are significant efforts to sequence reference microbial genomes from many body sites of healthy adults. To illustrate the utility of reference genomes when studying more complex metagenomes, we present a reference-based analysis of sequence reads generated from 55 shotgun metagenomes, selected from 5 major body sites, including 16 sub-sites. Interestingly, between 13% and 92% (62.3% average) of these shotgun reads were aligned to a then-complete list of 2780 reference genomes, including 1583 references for the human microbiome. However, no reference genome was universally found in all body sites. For any given metagenome, the body site-specific reference genomes, derived from the same body site as the sample, accounted for an average of 58.8% of the mapped reads. While different body sites did differ in abundant genera, proximal or symmetrical body sites were found to be most similar to one another. The extent of variation observed, both between individuals sampled within the same microenvironment, or at the same site within the same individual over time, calls into question comparative studies across individuals even if sampled at the same body site. This study illustrates the high utility of reference genomes and the need for further site-specific reference microbial genome sequencing, even within the already well-sampled human microbiome.}, }
@article {pmid24454486, year = {2013}, author = {Kim, BS and Bae, HS and Lim, CY and Kim, MJ and Seo, JG and Kim, JY and Kim, JE and Kim, H}, title = {Comparison of Gut Microbiota between Sasang Constitutions.}, journal = {Evidence-based complementary and alternative medicine : eCAM}, volume = {2013}, number = {}, pages = {171643}, pmid = {24454486}, issn = {1741-427X}, abstract = {The Sasang constitutional medicine has long been applied to diagnose and treat patients with various diseases. Studies have been conducted for establishment of scientific evidence supporting Sasang Constitutional (SC) diagnosis. Recent human microbiome studies have demonstrated individual variations of gut microbiota which can be dependent on lifestyle and health conditions. We hypothesized that gut microbial similarities and discrepancies may exist across SC types. We compared the difference of gut microbiota among three constitutions (So-Yang, So-Eum, and Tae-Eum), along with the investigation of anthropometric and biochemical parameters. Firmicutes and Bacteroidetes were predominant phyla in all SC types. The median plot analysis suggested that Firmicutes and Bacteroidetes appeared more abundant in SE and TE, respectively, in the male subjects of 20-29 years old. At the genus level, Bifidobacterium and Bacteroides manifested the difference between SE and TE types. For anthropometry, body weight, body mass index, and waist circumference of the TE type were significantly higher than those of the other types. Overall, findings indicated a possible link between SC types and gut microbiota within a narrow age range. Further investigations are deemed necessary to elucidate the influences of age, gender, and other factors in the context of SC types and gut microbiota.}, }
@article {pmid24451334, year = {2013}, author = {Vital, M and Penton, CR and Wang, Q and Young, VB and Antonopoulos, DA and Sogin, ML and Morrison, HG and Raffals, L and Chang, EB and Huffnagle, GB and Schmidt, TM and Cole, JR and Tiedje, JM}, title = {A gene-targeted approach to investigate the intestinal butyrate-producing bacterial community.}, journal = {Microbiome}, volume = {1}, number = {1}, pages = {8}, pmid = {24451334}, issn = {2049-2618}, support = {R01 DK097268/DK/NIDDK NIH HHS/United States ; }, abstract = {BACKGROUND: Butyrate, which is produced by the human microbiome, is essential for a well-functioning colon. Bacteria that produce butyrate are phylogenetically diverse, which hinders their accurate detection based on conventional phylogenetic markers. As a result, reliable information on this important bacterial group is often lacking in microbiome research.<br><br>RESULTS: In this study we describe a gene-targeted approach for 454 pyrotag sequencing and quantitative polymerase chain reaction for the final genes in the two primary bacterial butyrate synthesis pathways, butyryl-CoA:acetate CoA-transferase (but) and butyrate kinase (buk). We monitored the establishment and early succession of butyrate-producing communities in four patients with ulcerative colitis who underwent a colectomy with ileal pouch anal anastomosis and compared it with three control samples from healthy colons. All patients established an abundant butyrate-producing community (approximately 5% to 26% of the total community) in the pouch within the 2-month study, but patterns were distinctive among individuals. Only one patient harbored a community profile similar to the healthy controls, in which there was a predominance of but genes that are similar to reference genes from Acidaminococcus sp., Eubacterium sp., Faecalibacterium prausnitzii and Roseburia sp., and an almost complete absence of buk genes. Two patients were greatly enriched in buk genes similar to those of Clostridium butyricum and C. perfringens, whereas a fourth patient displayed abundant communities containing both genes. Most butyrate producers identified in previous studies were detected and the general patterns of taxa found were supported by 16S rRNA gene pyrotag analysis, but the gene-targeted approach provided more detail about the potential butyrate-producing members of the community.<br><br>CONCLUSIONS: The presented approach provides quantitative and genotypic insights into butyrate-producing communities and facilitates a more specific functional characterization of the intestinal microbiome. Furthermore, our analysis refines but and buk reference annotations found in central databases.}, }
@article {pmid24451062, year = {2013}, author = {Edlund, A and Yang, Y and Hall, AP and Guo, L and Lux, R and He, X and Nelson, KE and Nealson, KH and Yooseph, S and Shi, W and McLean, JS}, title = {An in vitro biofilm model system maintaining a highly reproducible species and metabolic diversity approaching that of the human oral microbiome.}, journal = {Microbiome}, volume = {1}, number = {1}, pages = {25}, pmid = {24451062}, issn = {2049-2618}, support = {R01 GM095373/GM/NIGMS NIH HHS/United States ; T90 DE022734/DE/NIDCR NIH HHS/United States ; }, abstract = {BACKGROUND: Our knowledge of microbial diversity in the human oral cavity has vastly expanded during the last two decades of research. However, much of what is known about the behavior of oral species to date derives from pure culture approaches and the studies combining several cultivated species, which likely does not fully reflect their function in complex microbial communities. It has been shown in studies with a limited number of cultivated species that early oral biofilm development occurs in a successional manner and that continuous low pH can lead to an enrichment of aciduric species. Observations that in vitro grown plaque biofilm microcosms can maintain similar pH profiles in response to carbohydrate addition as plaque in vivo suggests a complex microbial community can be established in the laboratory. In light of this, our primary goal was to develop a robust in vitro biofilm-model system from a pooled saliva inoculum in order to study the stability, reproducibility, and development of the oral microbiome, and its dynamic response to environmental changes from the community to the molecular level.<br><br>RESULTS: Comparative metagenomic analyses confirmed a high similarity of metabolic potential in biofilms to recently available oral metagenomes from healthy subjects as part of the Human Microbiome Project. A time-series metagenomic analysis of the taxonomic community composition in biofilms revealed that the proportions of major species at 3 hours of growth are maintained during 48 hours of biofilm development. By employing deep pyrosequencing of the 16S rRNA gene to investigate this biofilm model with regards to bacterial taxonomic diversity, we show a high reproducibility of the taxonomic carriage and proportions between: 1) individual biofilm samples; 2) biofilm batches grown at different dates; 3) DNA extraction techniques and 4) research laboratories.<br><br>CONCLUSIONS: Our study demonstrates that we now have the capability to grow stable oral microbial in vitro biofilms containing more than one hundred operational taxonomic units (OTU) which represent 60-80% of the original inoculum OTU richness. Previously uncultivated Human Oral Taxa (HOT) were identified in the biofilms and contributed to approximately one-third of the totally captured 16S rRNA gene diversity. To our knowledge, this represents the highest oral bacterial diversity reported for an in vitro model system so far. This robust model will help investigate currently uncultivated species and the known virulence properties for many oral pathogens not solely restricted to pure culture systems, but within multi-species biofilms.}, }
@article {pmid24450613, year = {2013}, author = {Fritz, JV and Desai, MS and Shah, P and Schneider, JG and Wilmes, P}, title = {From meta-omics to causality: experimental models for human microbiome research.}, journal = {Microbiome}, volume = {1}, number = {1}, pages = {14}, pmid = {24450613}, issn = {2049-2618}, abstract = {Large-scale 'meta-omic' projects are greatly advancing our knowledge of the human microbiome and its specific role in governing health and disease states. A myriad of ongoing studies aim at identifying links between microbial community disequilibria (dysbiosis) and human diseases. However, due to the inherent complexity and heterogeneity of the human microbiome, cross-sectional, case-control and longitudinal studies may not have enough statistical power to allow causation to be deduced from patterns of association between variables in high-resolution omic datasets. Therefore, to move beyond reliance on the empirical method, experiments are critical. For these, robust experimental models are required that allow the systematic manipulation of variables to test the multitude of hypotheses, which arise from high-throughput molecular studies. Particularly promising in this respect are microfluidics-based in vitro co-culture systems, which allow high-throughput first-pass experiments aimed at proving cause-and-effect relationships prior to testing of hypotheses in animal models. This review focuses on widely used in vivo, in vitro, ex vivo and in silico approaches to study host-microbial community interactions. Such systems, either used in isolation or in a combinatory experimental approach, will allow systematic investigations of the impact of microbes on the health and disease of the human host. All the currently available models present pros and cons, which are described and discussed. Moreover, suggestions are made on how to develop future experimental models that not only allow the study of host-microbiota interactions but are also amenable to high-throughput experimentation.}, }
@article {pmid24450540, year = {2013}, author = {Macklaim, JM and Fernandes, AD and Di Bella, JM and Hammond, JA and Reid, G and Gloor, GB}, title = {Comparative meta-RNA-seq of the vaginal microbiota and differential expression by Lactobacillus iners in health and dysbiosis.}, journal = {Microbiome}, volume = {1}, number = {1}, pages = {12}, pmid = {24450540}, issn = {2049-2618}, abstract = {BACKGROUND: Bacterial vaginosis (BV), the most common vaginal condition of reproductive-aged women, is associated with a highly diverse and heterogeneous microbiota. Here we present a proof-of-principle analysis to uncover the function of the microbiota using meta-RNA-seq to uncover genes and pathways that potentially differentiate healthy vaginal microbial communities from those in the dysbiotic state of bacterial vaginosis (BV).<br><br>RESULTS: The predominant organism, Lactobacillus iners, was present in both conditions and showed a differing expression profile in BV compared to healthy. Despite its minimal genome, L. iners differentially expressed over 10% of its gene complement. Notably, in a BV environment L. iners increased expression of a cholesterol-dependent cytolysin, and of mucin and glycerol transport and related metabolic enzymes. Genes belonging to a CRISPR system were greatly upregulated suggesting that bacteriophage influence the community. Reflective of L. iners, the bacterial community as a whole demonstrated a preference for glycogen and glycerol as carbon sources under BV conditions. The predicted end-products of metabolism under BV conditions include an abundance of succinate and other short-chain fatty-acids, while healthy conditions are predicted to largely contain lactic acid.<br><br>CONCLUSIONS: Our study underscores the importance of understanding the functional activity of the bacterial community in addition to characterizing the population structure when investigating the human microbiome.}, }
@article {pmid24439897, year = {2014}, author = {Degnan, PH and Barry, NA and Mok, KC and Taga, ME and Goodman, AL}, title = {Human gut microbes use multiple transporters to distinguish vitamin B12 analogs and compete in the gut.}, journal = {Cell host &amp; microbe}, volume = {15}, number = {1}, pages = {47-57}, pmid = {24439897}, issn = {1934-6069}, support = {R00 GM083343/GM/NIGMS NIH HHS/United States ; GM103574/GM/NIGMS NIH HHS/United States ; R01 GM103574/GM/NIGMS NIH HHS/United States ; R01 GM083303/GM/NIGMS NIH HHS/United States ; GM083343/GM/NIGMS NIH HHS/United States ; K01 DK089121/DK/NIDDK NIH HHS/United States ; DK089121/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Antibiosis/physiology ; Bacterial Outer Membrane Proteins/classification/*genetics/metabolism ; Bacteroides/genetics/metabolism ; Biological Transport ; Escherichia coli/genetics/metabolism ; Escherichia coli Proteins/classification/*genetics/metabolism ; Gastrointestinal Tract/*microbiology ; *Gene Expression Regulation, Bacterial ; *Genome, Bacterial ; Humans ; Membrane Transport Proteins/classification/*genetics/metabolism ; Mice ; *Microbiota ; Phylogeny ; Species Specificity ; Symbiosis/physiology ; Vitamin B 12/analogs &amp; derivatives/*metabolism ; }, abstract = {Genomic and metagenomic sequencing efforts, including human microbiome projects, reveal that microbes often encode multiple systems that appear to accomplish the same task. Whether these predictions reflect actual functional redundancies is unclear. We report that the prominent human gut symbiont Bacteroides thetaiotaomicron employs three functional, homologous vitamin B12 transporters that in at least two cases confer a competitive advantage in the presence of distinct B12 analogs (corrinoids). In the mammalian gut, microbial fitness can be determined by the presence or absence of a single transporter. The total number of distinct corrinoid transporter families in the human gut microbiome likely exceeds those observed in B. thetaiotaomicron by an order of magnitude. These results demonstrate that human gut microbes use elaborate mechanisms to capture and differentiate corrinoids in vivo and that apparent redundancies observed in these genomes can instead reflect hidden specificities that determine whether a microbe will colonize its host.}, }
@article {pmid24437411, year = {2014}, author = {Martinez, FD}, title = {The human microbiome. Early life determinant of health outcomes.}, journal = {Annals of the American Thoracic Society}, volume = {11 Suppl 1}, number = {Suppl 1}, pages = {S7-12}, pmid = {24437411}, issn = {2325-6621}, support = {R01 HL056177/HL/NHLBI NIH HHS/United States ; HL-56177/HL/NHLBI NIH HHS/United States ; }, mesh = {Animals ; Asthma/immunology/microbiology ; Gastrointestinal Tract/*microbiology ; Humans ; *Hygiene Hypothesis ; Inflammation/immunology/microbiology ; Lung/*microbiology ; Mice ; Microbiota/*immunology ; Mucous Membrane/*microbiology ; Obesity/immunology/microbiology ; }, abstract = {The development of new technologies to isolate and identify microbial genomes has markedly increased our understanding of the role of microbiomes in health and disease. The idea, first proposed as part of the hygiene hypothesis, that environmental microbes influence the developmental trajectories of the immune system in early life, has now been considerably extended and refined. The abundant microbiota present in mucosal surfaces, especially the gut, is actively selected by the host through complex receptor systems that respond differentially depending on the molecular patterns presented to mucosal cells. Germ-free mice are more likely to develop allergic airway inflammation and show alterations in normal motor control and anxiety. These effects can be reversed by neonatal microbial recolonization but remain unchanged if recolonization occurs in adults. What emerges from these recent studies is the discovery of a complex, major early environmental determinant of lifetime human phenotypes. To change the natural course of asthma, obesity, and other chronic inflammatory conditions, active manipulation of the extensive bacterial, phage, and fungal metagenomes present in mucosal surfaces may be required, specifically during the developing years. Domesticating the human microbiome and adapting it to our health needs may be a challenge akin to, but far more complex than, the one faced by humanity when a few dozen species of plants and animals were domesticated during the transition between hunter-gatherer and sedentary societies after the end of the Pleistocene era.}, }
@article {pmid24437408, year = {2014}, author = {Lynch, SV}, title = {Viruses and microbiome alterations.}, journal = {Annals of the American Thoracic Society}, volume = {11 Suppl 1}, number = {}, pages = {S57-60}, doi = {10.1513/AnnalsATS.201306-158MG}, pmid = {24437408}, issn = {2325-6621}, mesh = {Bacterial Infections/immunology ; Coinfection ; Gastrointestinal Tract/microbiology ; Humans ; Influenza A Virus, H1N1 Subtype ; Influenza, Human/*immunology ; *Lactobacillus ; Lung/immunology/*microbiology ; *Microbiota ; Respiratory Tract Infections/immunology/virology ; Virus Diseases/immunology ; }, abstract = {Viral infection represents a common and problematic health care issue, particularly in younger and senior populations. The respiratory tract is a major portal for microbial exposure, where viral infection can result in nonsymptomatic, mild, and self-limiting or severe and sometimes fatal infection. Although it is well established that virus-specific properties, such as longevity and replication kinetics, impact clinical manifestations, it is less well understood why distinct infectious outcomes may occur across a population of individuals infected with the same strain of virus. Emerging evidence points to interpersonal variation in pulmonary and gastrointestinal microbiome composition, and specifically to members of the Lactobacillus genus, as key components in defining respiratory viral infection outcomes. Moreover, human studies of airway microbiota after pH1N1 demonstrate that the composition of the respiratory microbiome can be modified by viral infection in a manner that enriches for pathogens associated with secondary bacterial infection. In this article, current knowledge in the field of human microbiome research, particularly as it pertains to respiratory viral infection, is reviewed.}, }
@article {pmid24437400, year = {2014}, author = {Segal, LN and Blaser, MJ}, title = {A brave new world: the lung microbiota in an era of change.}, journal = {Annals of the American Thoracic Society}, volume = {11 Suppl 1}, number = {Suppl 1}, pages = {S21-7}, pmid = {24437400}, issn = {2325-6621}, support = {UH2 AR57506/AR/NIAMS NIH HHS/United States ; UH2 AR057506/AR/NIAMS NIH HHS/United States ; K23 AI102970/AI/NIAID NIH HHS/United States ; UL1 TR000038/TR/NCATS NIH HHS/United States ; R01 DK090989/DK/NIDDK NIH HHS/United States ; }, mesh = {Anti-Bacterial Agents/*therapeutic use ; Gastrointestinal Tract/*microbiology ; Humans ; Immunity, Mucosal/immunology ; Inflammation ; Lung/immunology/*microbiology ; Metagenome ; *Microbiota ; Respiratory Mucosa/immunology/*microbiology ; }, abstract = {The development of culture-independent techniques has revolutionized our understanding of how our human cells interact with the even greater number of microbial inhabitants of our bodies. As part of this revolution, data are increasingly challenging the old dogma that in health, the lung mucosa is sterile. To understand how the lung microbiome may play a role in human health, we identified five major questions for lung microbiome research: (1) Is the lung sterile? (2) Is there a unique core microbiome in the lung? (3) How dynamic are the microbial populations? (4) How do pulmonary immune responses affect microbiome composition? and (5) Are the lungs influenced by the intestinal immune responses to the gut microbiome? From birth, we are exposed to continuous microbial challenges that shape our microbiome. In our changing environment, perturbation of the gut microbiome affects both human health and disease. With widespread antibiotic use, the ancient microbes that formerly resided within us are being lost, for example, Helicobacter pylori in the stomach. Animal models show that antibiotic exposure in early life has developmental consequences. Considering the potential effects of this altered microbiome on pulmonary responses will be critical for future investigations.}, }
@article {pmid24429972, year = {2014}, author = {Martín, R and Miquel, S and Langella, P and Bermúdez-Humarán, LG}, title = {The role of metagenomics in understanding the human microbiome in health and disease.}, journal = {Virulence}, volume = {5}, number = {3}, pages = {413-423}, pmid = {24429972}, issn = {2150-5608}, mesh = {*Disease ; *Health ; Host-Pathogen Interactions ; Humans ; Metagenomics/*methods ; *Microbiota ; Symbiosis ; }, abstract = {The term microbiome refers to the genetic material of the catalog of microbial taxa associated with humans. As in all ecosystems, the microbiota reaches a dynamic equilibrium in the human body, which can be altered by environmental factors and external stimuli. Metagenomics is a relatively new field of study of microbial genomes within diverse environmental samples, which is of increasing importance in microbiology. The introduction of this ecological perception of microbiology is the key to achieving real knowledge about the influence of the microbiota in human health and disease. The aim of this review is to summarize the link between the human microbiota (focusing on the intestinal, vaginal, skin, and airway body sites) and health from this ecological point of view, highlighting the contribution of metagenomics in the advance of this field.}, }
@article {pmid24422720, year = {2014}, author = {Selhub, EM and Logan, AC and Bested, AC}, title = {Fermented foods, microbiota, and mental health: ancient practice meets nutritional psychiatry.}, journal = {Journal of physiological anthropology}, volume = {33}, number = {1}, pages = {2}, pmid = {24422720}, issn = {1880-6805}, mesh = {*Diet ; *Fermentation ; Humans ; *Mental Health ; *Microbiota ; *Nutritional Physiological Phenomena ; }, abstract = {The purposeful application of fermentation in food and beverage preparation, as a means to provide palatability, nutritional value, preservative, and medicinal properties, is an ancient practice. Fermented foods and beverages continue to make a significant contribution to the overall patterns of traditional dietary practices. As our knowledge of the human microbiome increases, including its connection to mental health (for example, anxiety and depression), it is becoming increasingly clear that there are untold connections between our resident microbes and many aspects of physiology. Of relevance to this research are new findings concerning the ways in which fermentation alters dietary items pre-consumption, and in turn, the ways in which fermentation-enriched chemicals (for example, lactoferrin, bioactive peptides) and newly formed phytochemicals (for example, unique flavonoids) may act upon our own intestinal microbiota profile. Here, we argue that the consumption of fermented foods may be particularly relevant to the emerging research linking traditional dietary practices and positive mental health. The extent to which traditional dietary items may mitigate inflammation and oxidative stress may be controlled, at least to some degree, by microbiota. It is our contention that properly controlled fermentation may often amplify the specific nutrient and phytochemical content of foods, the ultimate value of which may associated with mental health; furthermore, we also argue that the microbes (for example, Lactobacillus and Bifidobacteria species) associated with fermented foods may also influence brain health via direct and indirect pathways.}, }
@article {pmid24422665, year = {2014}, author = {Beebe, K and Sampey, B and Watkins, SM and Milburn, M and Eckhart, AD}, title = {Understanding the apothecaries within: the necessity of a systematic approach for defining the chemical output of the human microbiome.}, journal = {Clinical and translational science}, volume = {7}, number = {1}, pages = {74-81}, pmid = {24422665}, issn = {1752-8062}, mesh = {Biotransformation ; Homeostasis ; Humans ; Metabolome ; Metagenome ; Microbial Interactions ; Microbiota/*physiology ; Quorum Sensing ; Xenobiotics/metabolism ; }, abstract = {The human microbiome harbors a massive diversity of microbes that effectively form an "organ" that strongly influences metabolism and immune function and hence, human health. Although the growing interest in the microbiome has chiefly arisen due to its impact on human physiology, the probable rules of operation are embedded in the roots of microbiology where chemical communication (i.e., with metabolites) is a dominant feature of coexistence. Indeed, recent examples in microbiome research offer the impression that the collective microbiome operates as an "apothecary," creating chemical concoctions that influence health and alter drug response. Although these principles are not unappreciated, the majority of emphasis is on metagenomics and research efforts often omit systematic efforts to interrogate the chemical component of the complex equation between microbial community and host phenotype. One of the reasons for this omission may be due to the inaccessibility to high-breadth, high-throughput, and scalable technologies. Since these technologies are now available, we propose that a more systematic effort to survey the host-microbiota chemical output be embedded into microbiome research as there is strong likelihood, and growing precedence, that this component may often be integral to developing our understanding of these ultimate apothecaries and how they impact human health.}, }
@article {pmid24416266, year = {2014}, author = {Finucane, MM and Sharpton, TJ and Laurent, TJ and Pollard, KS}, title = {A taxonomic signature of obesity in the microbiome? Getting to the guts of the matter.}, journal = {PloS one}, volume = {9}, number = {1}, pages = {e84689}, pmid = {24416266}, issn = {1932-6203}, mesh = {Adult ; Bacteria/classification ; Body Mass Index ; Case-Control Studies ; *Classification ; Gastrointestinal Tract/*microbiology ; Humans ; *Microbiota ; Obesity/*microbiology ; }, abstract = {Obesity is an important and intractable public health problem. In addition to the well-known risk factors of behavior, diet, and genetics, gut microbial communities were recently identified as another possible source of risk and a potential therapeutic target. However, human and animal-model studies have yielded conflicting results about the precise nature of associations between microbiome composition and obesity. In this paper, we use publicly available data from the Human Microbiome Project (HMP) and MetaHIT, both surveys of healthy adults that include obese individuals, plus two smaller studies that specifically examined lean versus obese adults. We find that inter-study variability in the taxonomic composition of stool microbiomes far exceeds differences between lean and obese individuals within studies. Our analyses further reveal a high degree of variability in stool microbiome composition and diversity across individuals. While we confirm the previously published small, but statistically significant, differences in phylum-level taxonomic composition between lean and obese individuals in several cohorts, we find no association between BMI and taxonomic composition of stool microbiomes in the larger HMP and MetaHIT datasets. We explore a range of different statistical techniques and show that this result is robust to the choice of methodology. Differences between studies are likely due to a combination of technical and clinical factors. We conclude that there is no simple taxonomic signature of obesity in the microbiota of the human gut.}, }
@article {pmid24401348, year = {2014}, author = {Klish, AJ and Porter, JA and Bashirelahi, N}, title = {What every dentist needs to know about the human microbiome and probiotics.}, journal = {General dentistry}, volume = {62}, number = {1}, pages = {30-36}, pmid = {24401348}, issn = {0363-6771}, mesh = {Gastrointestinal Tract/microbiology ; Humans ; *Microbiota/drug effects/physiology ; Mouth/microbiology ; Probiotics/pharmacology/*therapeutic use ; Respiratory System/microbiology ; }, abstract = {Bacterial cells in the human body outnumber human cells by a ratio of 10:1. Apart from their well-known pathogenic potential, bacteria are proving to be integral to the overall health of the body. Residential microbes have critical roles in diverse processes, such as nutrient harvesting, internal environment regulation, immune system development, neurological modulation, and drug metabolism, as well as providing protection against pathogens. There is a growing body of research on the microbiome and probiotic therapies to restore or augment these functions throughout the body. In particular, increasing numbers of bacterial species and bacterial interactions have been discovered in the oral cavity, and probiotic interventions for common dental problems such as caries, periodontal diseases, and oral malodor are being developed and reviewed.}, }
@article {pmid24390919, year = {2014}, author = {Sirota, I and Zarek, SM and Segars, JH}, title = {Potential influence of the microbiome on infertility and assisted reproductive technology.}, journal = {Seminars in reproductive medicine}, volume = {32}, number = {1}, pages = {35-42}, pmid = {24390919}, issn = {1526-4564}, support = {ZIE HD008737-12//Intramural NIH HHS/United States ; }, mesh = {Adult ; Anti-Bacterial Agents/therapeutic use ; Cytokines/physiology ; Embryo Implantation ; Embryo Transfer ; Estrogens/blood ; Female ; Humans ; Infertility, Female/*microbiology ; Lactobacillus ; Microbiota/*physiology ; Pregnancy ; Progesterone/blood ; *Reproductive Techniques, Assisted ; Vagina/microbiology ; Vaginosis, Bacterial/microbiology ; }, abstract = {Although an altered vaginal microbiota has been demonstrated to affect parturition, its role in assisted reproductive technologies is uncertain. Nevertheless, the effect of known pathogens such as Mycoplasma tuberculosis, Chlamydia trachomatis, and Neisseria gonorrhoeae is clear, causing subclinical changes thought to be risk factors in subfertility. The Human Microbiome Project (HMP) has allowed for metagenomic studies to aid in characterizing normal vaginal flora. Recent findings from the HMP demonstrate that many different species of Lactobacillus are present in the vaginal tract, with a few that predominate. Studies that characterize the vaginal microbiome in assisted reproductive technology support the hypothesis that colonizing the transfer-catheter tip with Lactobacillus crispatus at the time of embryo transfer may increase the rates of implantation and live birth rate while decreasing the rate of infection. In addition, there is some evidence that a progesterone-resistant endometrium might increase the risk of an abnormal vaginal microbiome.}, }
@article {pmid24390918, year = {2014}, author = {Reid, G}, title = {Modulating the vaginal microbiome: the need for a bridge between science and practice.}, journal = {Seminars in reproductive medicine}, volume = {32}, number = {1}, pages = {28-34}, doi = {10.1055/s-0033-1361820}, pmid = {24390918}, issn = {1526-4564}, mesh = {Anti-Bacterial Agents/adverse effects/therapeutic use ; Female ; Humans ; Lactobacillus/physiology ; Microbiota/*physiology ; Pregnancy ; Probiotics/therapeutic use ; Vagina/*microbiology ; Vaginosis, Bacterial/drug therapy/microbiology ; }, abstract = {Infections of the urinary and reproductive tracts continue to afflict hundreds of millions of women and girls each year. For those fortunate enough to have access to medical care, the diagnostic and treatment measures used on them have changed little in 40 years and remain far from adequate. The development of alternatives, such as probiotics, has been hindered by lack of funding, but now face bureaucratic barriers that reflect an outdated regulatory system more concerned with policies than care for the patient. The technological advances emerging from human microbiome studies are making it possible to generate a completely new understanding of how microbes interact with the host, what influences them, and when the result is an aberration requiring intervention. But until bridges are built between scientific progress and practice, it is women and girls who will continue to receive suboptimal care for their often persistent and debilitating conditions.}, }
@article {pmid24390916, year = {2014}, author = {Prince, AL and Antony, KM and Ma, J and Aagaard, KM}, title = {The microbiome and development: a mother's perspective.}, journal = {Seminars in reproductive medicine}, volume = {32}, number = {1}, pages = {14-22}, doi = {10.1055/s-0033-1361818}, pmid = {24390916}, issn = {1526-4564}, mesh = {Child Development/*physiology ; Female ; Humans ; Infant, Newborn ; Microbiota/*physiology ; *Mothers ; Placenta/microbiology ; Pregnancy ; Premature Birth ; }, abstract = {Dysbiosis of the microbiome has been associated with type II diabetes mellitus, obesity, inflammatory bowel disorders, and colorectal cancer, and recently, the Human Microbiome Project Consortium has helped to define a healthy microbiome. Now research has begun to investigate how the microbiome is established, and in this article, we will discuss the maternal influences on the establishment of the microbiome. The inoculation of an individual's microbiome is highly dependent on the maternal microbiome, and changes occur in the maternal microbiome during pregnancy that may help to shape the neonatal microbiome. Further, we consider how mode of delivery may shape the developing microbiome of a neonate, and we end by discussing how the microbiome may impact preterm birth and the possibility of bacterial colonization of the placenta. Although the current literature demonstrates that the transformation of the maternal microbiome during pregnancy effects the establishment of the neonatal microbiome, further research is needed to explore how the microbiome shapes our metabolism and developing immune system.}, }
@article {pmid24388028, year = {2014}, author = {Khanna, S and Tosh, PK}, title = {A clinician's primer on the role of the microbiome in human health and disease.}, journal = {Mayo Clinic proceedings}, volume = {89}, number = {1}, pages = {107-114}, doi = {10.1016/j.mayocp.2013.10.011}, pmid = {24388028}, issn = {1942-5546}, mesh = {Animals ; Autoimmune Diseases/*microbiology ; Causality ; Clinical Medicine/education ; Clostridioides difficile ; Clostridium Infections/*microbiology ; Comorbidity ; Curriculum ; Drug Resistance, Multiple ; Humans ; Hypersensitivity/*microbiology ; Inflammatory Bowel Diseases/*microbiology ; Intestinal Diseases/*microbiology ; *Microbiota ; Neuropsychiatry ; Obesity/*microbiology ; United States ; }, abstract = {The importance of the commensal microbiota that colonizes the skin, gut, and mucosal surfaces of the human body is being increasingly recognized through a rapidly expanding body of science studying the human microbiome. Although, at first glance, these discoveries may seem esoteric, the clinical implications of the microbiome in human health and disease are becoming clear. As such, it will soon be important for practicing clinicians to have an understanding of the basic concepts of the human microbiome and its relation to human health and disease. In this Concise Review, we provide a brief introduction to clinicians of the concepts underlying this burgeoning scientific field and briefly explore specific disease states for which the potential role of the human microbiome is becoming increasingly evident, including Clostridium difficile infection, inflammatory bowel disease, colonization with multidrug-resistant organisms, obesity, allergic diseases, autoimmune diseases, and neuropsychiatric illnesses, and we also discuss current and future roles of microbiome restorative therapies.}, }
@article {pmid24386477, year = {2013}, author = {Ramakrishnan, VR and Feazel, LM and Gitomer, SA and Ir, D and Robertson, CE and Frank, DN}, title = {The microbiome of the middle meatus in healthy adults.}, journal = {PloS one}, volume = {8}, number = {12}, pages = {e85507}, pmid = {24386477}, issn = {1932-6203}, support = {R21 HG005964/HG/NHGRI NIH HHS/United States ; HG005964/HG/NHGRI NIH HHS/United States ; }, mesh = {Adolescent ; Adult ; Aged ; Female ; Gram-Positive Bacteria/classification/*genetics/isolation &amp; purification ; Humans ; Male ; *Microbiota ; Middle Aged ; Nasal Cavity/*microbiology ; Paranasal Sinuses/*microbiology ; RNA, Bacterial/*genetics ; RNA, Ribosomal, 16S/*genetics ; }, abstract = {Rhinitis and rhinosinusitis are multifactorial disease processes in which bacteria may play a role either in infection or stimulation of the inflammatory process. Rhinosinusitis has been historically studied with culture-based techniques, which have implicated several common pathogens in disease states. More recently, the NIH Human Microbiome Project has examined the microbiome at a number of accessible body sites, and demonstrated differences among healthy and diseased patients. Recent DNA-based sinus studies have suggested that healthy sinuses are not sterile, as was previously believed, but the normal sinonasal microbiome has yet to be thoroughly examined. Middle meatus swab specimens were collected from 28 consecutive patients presenting with no signs or symptoms of rhinosinusitis. Bacterial colonization was assessed in these specimens using quantitative PCR and 16S rRNA pyrosequencing. All subjects were positive for bacterial colonization of the middle meatus. Staphylococcus aureus, Staphylococcus epidermidis and Propionibacterium acnes were the most prevalent and abundant microorganisms detected. Rich and diverse bacterial assemblages are present in the sinonasal cavity in the normal state, including opportunistic pathogens typically found in the nasopharynx. This work helps establish a baseline for understanding how the sinonasal microbiome may impact diseases of the upper airways.}, }
@article {pmid24379111, year = {2014}, author = {Alverdy, J and Gilbert, J and DeFazio, JR and Sadowsky, MJ and Chang, EB and Morowitz, MJ and Teitelbaum, DH}, title = {Proceedings of the 2013 A.S.P.E.N. Research workshop: the interface between nutrition and the gut microbiome: implications and applications for human health [corrected].}, journal = {JPEN. Journal of parenteral and enteral nutrition}, volume = {38}, number = {2}, pages = {167-178}, pmid = {24379111}, issn = {1941-2444}, support = {R13 DK097953/DK/NIDDK NIH HHS/United States ; 1R13DK097953-01/DK/NIDDK NIH HHS/United States ; }, mesh = {Clostridioides difficile/growth &amp; development/isolation &amp; purification ; Enterocolitis, Necrotizing/microbiology ; Gastrointestinal Tract/*microbiology ; Host-Pathogen Interactions ; Humans ; Infant ; Inflammatory Bowel Diseases/microbiology ; *Microbiota ; Models, Biological ; *Nutritional Status ; Parenteral Nutrition ; }, abstract = {The human and earth microbiomes are among the most important biological agents in understanding and preventing disease. Technology is advancing at a fast pace and allowing for high-resolution analysis of the composition and function of our microbial partners across regions, space, and time. Bioinformaticists and biostatisticians are developing ever more elegant displays to understand the generated megadatasets. A virtual cyberinfrastructure of search engines to cross-reference the rapidly developing data is emerging in line with technologic advances. Nutrition science will reap the benefits of this new field, and its role in preserving the earth and the humans who inhabit it will become evidently clear. In this report we highlight some of the topics of an A.S.P.E.N.-sponsored symposium held during Clinical Nutrition Week in 2013 that address the importance of the human microbiome to human health and disease.}, }
@article {pmid24365095, year = {2014}, author = {Gargano, LM and Hughes, JM}, title = {Microbial origins of chronic diseases.}, journal = {Annual review of public health}, volume = {35}, number = {}, pages = {65-82}, doi = {10.1146/annurev-publhealth-032013-182426}, pmid = {24365095}, issn = {1545-2093}, support = {T32 AI007610/AI/NIAID NIH HHS/United States ; }, mesh = {Cardiovascular Diseases/microbiology ; Chronic Disease/*epidemiology ; Communicable Diseases/*complications ; Dementia/microbiology ; Gastrointestinal Diseases/microbiology ; Humans ; Infections/*complications ; Mental Disorders/microbiology ; *Microbiota ; Neoplasms/microbiology ; Obesity/microbiology ; Periodontal Diseases/microbiology ; Public Health ; }, abstract = {Chronic diseases such as cardiovascular disease and cancer are among the leading causes of death worldwide and have been on the rise over the past decade. Associations between microbial agents and development of chronic diseases have been made in the past, and new connections are currently being assessed. Investigators are examining the relationship between infectious agents and chronic disease using new technologies with more rigor and specificity. This review examines microbial agents' links to and associations with cardiovascular diseases, cancer, neurodegenerative diseases, renal diseases, psychiatric disorders, and obesity and addresses the important role of the human microbiome in maintenance of health and its potential role in chronic diseases. These associations and relationships will impact future research priorities, surveillance approaches, treatment strategies, and prevention programs for chronic diseases.}, }
@article {pmid24349412, year = {2013}, author = {Culligan, EP and Sleator, RD and Marchesi, JR and Hill, C}, title = {Functional environmental screening of a metagenomic library identifies stlA; a unique salt tolerance locus from the human gut microbiome.}, journal = {PloS one}, volume = {8}, number = {12}, pages = {e82985}, pmid = {24349412}, issn = {1932-6203}, mesh = {Adult ; Bacterial Proteins/*genetics ; Datasets as Topic ; *Genes, Bacterial ; *Genetic Loci ; Humans ; Intestines/*microbiology ; Male ; Metagenomics/methods ; Microbiota/*genetics ; Salt Tolerance/*genetics ; }, abstract = {Functional environmental screening of metagenomic libraries is a powerful means to identify and assign function to novel genes and their encoded proteins without any prior sequence knowledge. In the current study we describe the identification and subsequent analysis of a salt-tolerant clone from a human gut metagenomic library. Following transposon mutagenesis we identified an unknown gene (stlA, for "salt tolerance locus A") with no current known homologues in the databases. Subsequent cloning and expression in Escherichia coli MKH13 revealed that stlA confers a salt tolerance phenotype in its surrogate host. Furthermore, a detailed in silico analysis was also conducted to gain additional information on the properties of the encoded StlA protein. The stlA gene is rare when searched against human metagenome datasets such as MetaHit and the Human Microbiome Project and represents a novel and unique salt tolerance determinant which appears to be found exclusively in the human gut environment.}, }
@article {pmid24319142, year = {2014}, author = {Zhang, Q and Doak, TG and Ye, Y}, title = {Expanding the catalog of cas genes with metagenomes.}, journal = {Nucleic acids research}, volume = {42}, number = {4}, pages = {2448-2459}, pmid = {24319142}, issn = {1362-4962}, mesh = {CRISPR-Associated Proteins/classification/*genetics ; CRISPR-Cas Systems ; Feces/microbiology ; Genes, Bacterial ; Genome, Bacterial ; Humans ; *Metagenome ; Metagenomics/methods ; Microbiota ; Mouth/microbiology ; }, abstract = {The CRISPR (clusters of regularly interspaced short palindromic repeats)-Cas adaptive immune system is an important defense system in bacteria, providing targeted defense against invasions of foreign nucleic acids. CRISPR-Cas systems consist of CRISPR loci and cas (CRISPR-associated) genes: sequence segments of invaders are incorporated into host genomes at CRISPR loci to generate specificity, while adjacent cas genes encode proteins that mediate the defense process. We pursued an integrated approach to identifying putative cas genes from genomes and metagenomes, combining similarity searches with genomic neighborhood analysis. Application of our approach to bacterial genomes and human microbiome datasets allowed us to significantly expand the collection of cas genes: the sequence space of the Cas9 family, the key player in the recently engineered RNA-guided platforms for genome editing in eukaryotes, is expanded by at least two-fold with metagenomic datasets. We found genes in cas loci encoding other functions, for example, toxins and antitoxins, confirming the recently discovered potential of coupling between adaptive immunity and the dormancy/suicide systems. We further identified 24 novel Cas families; one novel family contains 20 proteins, all identified from the human microbiome datasets, illustrating the importance of metagenomics projects in expanding the diversity of cas genes.}, }
@article {pmid24305737, year = {2014}, author = {Cai, L and Ju, F and Zhang, T}, title = {Tracking human sewage microbiome in a municipal wastewater treatment plant.}, journal = {Applied microbiology and biotechnology}, volume = {98}, number = {7}, pages = {3317-3326}, doi = {10.1007/s00253-013-5402-z}, pmid = {24305737}, issn = {1432-0614}, mesh = {Bacteria/*classification/genetics ; Cluster Analysis ; DNA, Bacterial/chemistry/genetics ; DNA, Ribosomal/chemistry/genetics ; Hong Kong ; Humans ; *Metagenome ; *Microbiota ; Molecular Sequence Data ; Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; Sewage/*microbiology ; Water Purification/*methods ; }, abstract = {Human sewage pollution is a major threat to public health because sewage always comes with pathogens. Human sewage is usually received and treated by wastewater treatment plants (WWTPs) to control pathogenic risks and ameliorate environmental health. However, untreated sewage that flows into water environments may cause serious waterborne diseases, as reported in India and Bangladesh. To examine the fate of the human sewage microbiome in a local municipal WWTP of Hong Kong, we used massively parallel sequencing of 16S rRNA gene to systematically profile microbial communities in samples from three sections (i.e., influent, activated sludge, and effluent) obtained monthly throughout 1 year. The results indicated that: (1) influent sewage bacterial profile reflected the human microbiome; (2) human gut bacterial community was the dominant force shaping influent sewage bacterial profile; (3) most human sewage bacteria could be effectively removed by the WWTP; (4) a total of 75 genera were profiled as potentially pathogenic bacteria, most of which were still present in the effluent although at a very low level; (5) a grouped pattern of bacterial community was observed among the same section samples but a dispersed pattern was found among the different section samples; and (6) activated sludge was less affected by the influent sewage bacteria, but it showed a significant impact on the effluent bacteria. All of these findings provide novel insights toward a mechanistic understanding of the fate of human sewage microbiome in the WWTP.}, }
@article {pmid24302613, year = {2014}, author = {Bultman, SJ}, title = {Emerging roles of the microbiome in cancer.}, journal = {Carcinogenesis}, volume = {35}, number = {2}, pages = {249-255}, pmid = {24302613}, issn = {1460-2180}, support = {P30 ES010126/ES/NIEHS NIH HHS/United States ; CA125237/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Anti-Bacterial Agents/*therapeutic use ; Gastrointestinal Tract/drug effects/*microbiology ; Humans ; Mice ; Microbiota/*drug effects ; Neoplasms/drug therapy/*microbiology ; }, abstract = {Gene-environment interactions underlie cancer susceptibility and progression. Yet, we still have limited knowledge of which environmental factors are important and how they function during tumorigenesis. In this respect, the microbial communities that inhabit our gastrointestinal tract and other body sites have been unappreciated until recently. However, our microbiota are environmental factors that we are exposed to continuously, and human microbiome studies have revealed significant differences in the relative abundance of certain microbes in cancer cases compared with controls. To characterize the function of microbiota in carcinogenesis, mouse models of cancer have been treated with antibiotics. They have also been maintained in a germfree state or have been colonized with specific bacteria in specialized (gnotobiotic) facilities. These studies demonstrate that microbiota can increase or decrease cancer susceptibility and progression by diverse mechanisms such as by modulating inflammation, influencing the genomic stability of host cells and producing metabolites that function as histone deacetylase inhibitors to epigenetically regulate host gene expression. One might consider microbiota as tractable environmental factors because they are highly quantifiable and relatively stable within an individual compared with our exposures to external agents. At the same time, however, diet can modulate the composition of microbial communities within our gut, and this supports the idea that probiotics and prebiotics can be effective chemoprevention strategies. The trajectory of where the current work is headed suggests that microbiota will continue to provide insight into the basic mechanisms of carcinogenesis and that microbiota will also become targets for therapeutic intervention.}, }
@article {pmid24298178, year = {2013}, author = {Landy, J and Hart, A}, title = {The microbiome in inflammatory bowel disease and beyond.}, journal = {Clinical medicine (London, England)}, volume = {13 Suppl 6}, number = {}, pages = {s29-31}, doi = {10.7861/clinmedicine.13-6-s29}, pmid = {24298178}, issn = {1473-4893}, mesh = {Anti-Bacterial Agents ; Colitis, Ulcerative ; Crohn Disease ; Humans ; *Inflammatory Bowel Diseases/immunology ; *Microbiota ; Probiotics ; }, abstract = {The diverse and complex community of microorganisms that has co-evolved with the human gut is vital to intestinal functioning, and disturbances in the microbiota and its relationship with the host immune system have been linked to inflammatory bowel diseases, including Crohn's disease and ulcerative colitis. This has suggested several treatment options, including antibiotics, probiotics and faecal transplantation. The human microbiome project has been established to enable comprehensive characterisation of the human microbiota and in the coming years, knowledge in this area is expected to continue to expand.}, }
@article {pmid24281660, year = {2014}, author = {Zvanych, R and Lukenda, N and Kim, JJ and Li, X and Petrof, EO and Khan, WI and Magarvey, NA}, title = {Small molecule immunomodulins from cultures of the human microbiome member Lactobacillus plantarum.}, journal = {The Journal of antibiotics}, volume = {67}, number = {1}, pages = {85-88}, doi = {10.1038/ja.2013.126}, pmid = {24281660}, issn = {1881-1469}, support = {//Canadian Institutes of Health Research/Canada ; }, mesh = {Animals ; Dipeptides/chemistry/isolation &amp; purification/pharmacology ; Humans ; Immunologic Factors/chemistry/isolation &amp; purification/*pharmacology ; Inflammation Mediators/metabolism ; Interferon-gamma/*metabolism ; Lactobacillus plantarum/*metabolism ; Male ; *Metabolomics ; Mice ; Mice, Inbred C57BL ; Microbiota ; Phenylalanine/chemistry/isolation &amp; purification/pharmacology ; Principal Component Analysis ; Pyrrolidonecarboxylic Acid/chemistry ; Tryptophan/chemistry/isolation &amp; purification/pharmacology ; }, abstract = {Lactobacillus plantarum strains are noted for their presence in the human gastrointestinal tract and are distinguished for their immunomodulatory actions and therapeutic applications. Despite the uncertainty in the underlining molecular mechanisms, recent evidence suggests that L. plantarum secretes immunomodulatory agents that alter immunological signaling cascades. Elaboration of these metabolic products from L. plantarum strain WCFS1 was demonstrated previously to correlate with the mid-log-stationary transition, perhaps consistent with secondary metabolite expression. Here, we present the metabolomic shifts revealed by principal component analysis that correspond to the mid-log-stationary transition of L. plantarum, and identify pyroglutamic (pyro) dipeptides within this transition as correlative with the immunomodulatory actions. Four of these (pyro-phenylalanine, pyro-leucine, pyro-isoleucine, pyro-tryptophan) were characterized and the two dominant members, pyro-phenylalanine and pyro-tryptophan, were directly interrogated for immunomodulatory activity through in vivo administration using C57BL/6 mice. Administration of these compounds resulted in decreased production of pro-inflammatory cytokine interferon (IFN)-gamma, which is of noted importance in gastrointestinal immune homeostasis.}, }
@article {pmid24278398, year = {2013}, author = {Fontenete, S and Guimarães, N and Leite, M and Figueiredo, C and Wengel, J and Filipe Azevedo, N}, title = {Hybridization-based detection of Helicobacter pylori at human body temperature using advanced locked nucleic acid (LNA) probes.}, journal = {PloS one}, volume = {8}, number = {11}, pages = {e81230}, pmid = {24278398}, issn = {1932-6203}, mesh = {Flow Cytometry ; Helicobacter Infections/diagnosis ; Helicobacter pylori/*genetics ; Humans ; In Situ Hybridization, Fluorescence/*methods ; Microscopy, Fluorescence ; Nucleic Acid Hybridization ; Nucleic Acid Probes ; Stomach/microbiology ; }, abstract = {The understanding of the human microbiome and its influence upon human life has long been a subject of study. Hence, methods that allow the direct detection and visualization of microorganisms and microbial consortia (e.g. biofilms) within the human body would be invaluable. In here, we assessed the possibility of developing a variant of fluorescence in situ hybridization (FISH), named fluorescence in vivo hybridization (FIVH), for the detection of Helicobacter pylori. Using oligonucleotide variations comprising locked nucleic acids (LNA) and 2'-O-methyl RNAs (2'OMe) with two types of backbone linkages (phosphate or phosphorothioate), we were able to successfully identify two probes that hybridize at 37 °C with high specificity and sensitivity for H. pylori, both in pure cultures and in gastric biopsies. Furthermore, the use of this type of probes implied that toxic compounds typically used in FISH were either found to be unnecessary or could be replaced by a non-toxic substitute. We show here for the first time that the use of advanced LNA probes in FIVH conditions provides an accurate, simple and fast method for H. pylori detection and location, which could be used in the future for potential in vivo applications either for this microorganism or for others.}, }
@article {pmid24266656, year = {2013}, author = {Petschow, B and Doré, J and Hibberd, P and Dinan, T and Reid, G and Blaser, M and Cani, PD and Degnan, FH and Foster, J and Gibson, G and Hutton, J and Klaenhammer, TR and Ley, R and Nieuwdorp, M and Pot, B and Relman, D and Serazin, A and Sanders, ME}, title = {Probiotics, prebiotics, and the host microbiome: the science of translation.}, journal = {Annals of the New York Academy of Sciences}, volume = {1306}, number = {1}, pages = {1-17}, pmid = {24266656}, issn = {1749-6632}, support = {U01 AT002388/AT/NCCIH NIH HHS/United States ; R13AT007899/AT/NCCIH NIH HHS/United States ; U01 AT002133/AT/NCCIH NIH HHS/United States ; R13 AT007899/AT/NCCIH NIH HHS/United States ; U01 AT002952/AT/NCCIH NIH HHS/United States ; }, mesh = {Cognition ; Congresses as Topic ; Depression/therapy ; Diabetes Mellitus/therapy ; Humans ; Intestines/microbiology ; Lactose Intolerance/therapy ; Mental Health ; *Microbiota ; Obesity/therapy ; Prebiotics/*microbiology ; Probiotics/*therapeutic use ; *Translational Research, Biomedical ; }, abstract = {Recent advances in our understanding of the community structure and function of the human microbiome have implications for the potential role of probiotics and prebiotics in promoting human health. A group of experts recently met to review the latest advances in microbiota/microbiome research and discuss the implications for development of probiotics and prebiotics, primarily as they relate to effects mediated via the intestine. The goals of the meeting were to share recent advances in research on the microbiota, microbiome, probiotics, and prebiotics, and to discuss these findings in the contexts of regulatory barriers, evolving healthcare environments, and potential effects on a variety of health topics, including the development of obesity and diabetes; the long-term consequences of exposure to antibiotics early in life to the gastrointestinal (GI) microbiota; lactose intolerance; and the relationship between the GI microbiota and the central nervous system, with implications for depression, cognition, satiety, and mental health for people living in developed and developing countries. This report provides an overview of these discussions.}, }
@article {pmid24225315, year = {2014}, author = {Caspi, R and Altman, T and Billington, R and Dreher, K and Foerster, H and Fulcher, CA and Holland, TA and Keseler, IM and Kothari, A and Kubo, A and Krummenacker, M and Latendresse, M and Mueller, LA and Ong, Q and Paley, S and Subhraveti, P and Weaver, DS and Weerasinghe, D and Zhang, P and Karp, PD}, title = {The MetaCyc database of metabolic pathways and enzymes and the BioCyc collection of Pathway/Genome Databases.}, journal = {Nucleic acids research}, volume = {42}, number = {Database issue}, pages = {D459-71}, pmid = {24225315}, issn = {1362-4962}, support = {GM077678/GM/NIGMS NIH HHS/United States ; R01 GM080746/GM/NIGMS NIH HHS/United States ; GM088849/GM/NIGMS NIH HHS/United States ; U24 GM077678/GM/NIGMS NIH HHS/United States ; GM75742/GM/NIGMS NIH HHS/United States ; GM080746/GM/NIGMS NIH HHS/United States ; }, mesh = {*Databases, Chemical ; Enzymes/chemistry/classification/*metabolism ; Gene Ontology ; Genome ; Internet ; Kinetics ; *Metabolic Networks and Pathways/genetics ; Polysaccharides/metabolism ; Software ; }, abstract = {The MetaCyc database (MetaCyc.org) is a comprehensive and freely accessible database describing metabolic pathways and enzymes from all domains of life. MetaCyc pathways are experimentally determined, mostly small-molecule metabolic pathways and are curated from the primary scientific literature. MetaCyc contains >2100 pathways derived from >37,000 publications, and is the largest curated collection of metabolic pathways currently available. BioCyc (BioCyc.org) is a collection of >3000 organism-specific Pathway/Genome Databases (PGDBs), each containing the full genome and predicted metabolic network of one organism, including metabolites, enzymes, reactions, metabolic pathways, predicted operons, transport systems and pathway-hole fillers. Additions to BioCyc over the past 2 years include YeastCyc, a PGDB for Saccharomyces cerevisiae, and 891 new genomes from the Human Microbiome Project. The BioCyc Web site offers a variety of tools for querying and analysis of PGDBs, including Omics Viewers and tools for comparative analysis. New developments include atom mappings in reactions, a new representation of glycan degradation pathways, improved compound structure display, better coverage of enzyme kinetic data, enhancements of the Web Groups functionality, improvements to the Omics viewers, a new representation of the Enzyme Commission system and, for the desktop version of the software, the ability to save display states.}, }
@article {pmid24217035, year = {2013}, author = {Versalovic, J}, title = {The human microbiome and probiotics: implications for pediatrics.}, journal = {Annals of nutrition &amp; metabolism}, volume = {63 Suppl 2}, number = {}, pages = {42-52}, doi = {10.1159/000354899}, pmid = {24217035}, issn = {1421-9697}, mesh = {Celiac Disease ; Child ; Clostridioides difficile ; Diet ; Enterocolitis, Necrotizing ; Gastroenterology ; Humans ; Immunity ; Inflammatory Bowel Diseases ; Intestines/microbiology ; Irritable Bowel Syndrome ; *Microbiota ; *Pediatrics ; *Probiotics ; }, abstract = {Steady advances in our knowledge of the composition and function of the human microbiome at multiple body sites including the gut, skin and airways will likely contribute to our understanding of mechanisms of probiotic action by beneficial microbes. Microbe:microbe and microbe:human interactions are important considerations as we select probiotics for pediatric patients in the future. Although our knowledge about the composition of the microbiome is progressing rapidly, many gaps exist about the functional capacity and metabolic machinery of the human microbiome. Based on a limited amount of data, probiotics appear capable of altering the composition and function of the microbiome. Probiotics may be part of dietary strategies that combine ways to enhance microbiome function with nutrients that may be converted to active compounds promoting human health. Probiotics have yielded beneficial effects in numerous studies in the context of different diseases in pediatric gastroenterology. These disease states include necrotizing enterocolitis, antibiotic-associated diarrhea and colitis, acute gastroenteritis and irritable bowel syndrome. In the skin and airways, it is unclear if probiotics can affect the function of the microbiome to reduce the impact of diseases such as asthma and atopic dermatitis. An enhanced understanding of the effects of probiotics on the microbiome should facilitate selection of optimal probiotic strains for specific diseases in the future.}, }
@article {pmid24203705, year = {2014}, author = {Huang, K and Brady, A and Mahurkar, A and White, O and Gevers, D and Huttenhower, C and Segata, N}, title = {MetaRef: a pan-genomic database for comparative and community microbial genomics.}, journal = {Nucleic acids research}, volume = {42}, number = {Database issue}, pages = {D617-24}, pmid = {24203705}, issn = {1362-4962}, support = {P30 DK043351/DK/NIDDK NIH HHS/United States ; U54HG004969/HG/NHGRI NIH HHS/United States ; R01HG005969/HG/NHGRI NIH HHS/United States ; HHSN272200900018C/AI/NIAID NIH HHS/United States ; }, mesh = {Archaea/classification ; Bacteria/classification ; *Databases, Genetic ; *Genome, Archaeal ; *Genome, Bacterial ; Genomics ; Internet ; Metagenomics ; Microbiota ; Molecular Sequence Annotation ; Multigene Family ; Phylogeny ; }, abstract = {Microbial genome sequencing is one of the longest-standing areas of biological database development, but high-throughput, low-cost technologies have increased its throughput to an unprecedented number of new genomes per year. Several thousand microbial genomes are now available, necessitating new approaches to organizing information on gene function, phylogeny and microbial taxonomy to facilitate downstream biological interpretation. MetaRef, available at http://metaref.org, is a novel online resource systematically cataloguing a comprehensive pan-genome of all microbial clades with sequenced isolates. It organizes currently available draft and finished bacterial and archaeal genomes into quality-controlled clades, reports all core and pan gene families at multiple levels in the resulting taxonomy, and it annotates families' conservation, phylogeny and consensus functional information. MetaRef also provides a comprehensive non-redundant reference gene catalogue for metagenomic studies, including the abundance and prevalence of all gene families in the >700 shotgun metagenomic samples of the Human Microbiome Project. This constitutes a systematic mapping of clade-specific microbial functions within the healthy human microbiome across multiple body sites and can be used as reference for identifying potential functional biomarkers in disease-associate microbiomes. MetaRef provides all information both as an online browsable resource and as downloadable sequences and tabular data files that can be used for subsequent offline studies.}, }
@article {pmid24196194, year = {2013}, author = {Wang, Q and Venkataramanan, KP and Huang, H and Papoutsakis, ET and Wu, CH}, title = {Transcription factors and genetic circuits orchestrating the complex, multilayered response of Clostridium acetobutylicum to butanol and butyrate stress.}, journal = {BMC systems biology}, volume = {7}, number = {}, pages = {120}, pmid = {24196194}, issn = {1752-0509}, mesh = {Amino Acids/biosynthesis ; Butanols/*pharmacology ; Butyrates/*pharmacology ; Clostridium acetobutylicum/*drug effects/*genetics/metabolism/physiology ; DNA, Bacterial/biosynthesis ; Gene Expression Regulation, Bacterial/drug effects/genetics ; Gene Regulatory Networks/*drug effects ; Genomics ; Regulon/drug effects/genetics ; Stress, Physiological/*drug effects/genetics ; Transcription Factors/*metabolism ; }, abstract = {BACKGROUND: Organisms of the genus Clostridium are Gram-positive endospore formers of great importance to the carbon cycle, human normo- and pathophysiology, but also in biofuel and biorefinery applications. Exposure of Clostridium organisms to chemical and in particular toxic metabolite stress is ubiquitous in both natural (such as in the human microbiome) and engineered environments, engaging both the general stress response as well as specialized programs. Yet, despite its fundamental and applied significance, it remains largely unexplored at the systems level.<br><br>RESULTS: We generated a total of 96 individual sets of microarray data examining the transcriptional changes in C. acetobutylicum, a model Clostridium organism, in response to three levels of chemical stress from the native metabolites, butanol and butyrate. We identified 164 significantly differentially expressed transcriptional regulators and detailed the cellular programs associated with general and stressor-specific responses, many previously unexplored. Pattern-based, comparative genomic analyses enabled us, for the first time, to construct a detailed picture of the genetic circuitry underlying the stress response. Notably, a list of the regulons and DNA binding motifs of the stress-related transcription factors were identified: two heat-shock response regulators, HrcA and CtsR; the SOS response regulator LexA; the redox sensor Rex; and the peroxide sensor PerR. Moreover, several transcriptional regulators controlling stress-responsive amino acid and purine metabolism and their regulons were also identified, including ArgR (arginine biosynthesis and catabolism regulator), HisR (histidine biosynthesis regulator), CymR (cysteine metabolism repressor) and PurR (purine metabolism repressor).<br><br>CONCLUSIONS: Using an exceptionally large set of temporal transcriptional data and regulon analyses, we successfully built a STRING-based stress response network model integrating important players for the general and specialized metabolite stress response in C. acetobutylicum. Since the majority of the transcription factors and their target genes are highly conserved in other organisms of the Clostridium genus, this network would be largely applicable to other Clostridium organisms. The network informs the molecular basis of Clostridium responses to toxic metabolites in natural ecosystems and the microbiome, and will facilitate the construction of genome-scale models with added regulatory-network dimensions to guide the development of tolerant strains.}, }
@article {pmid24180596, year = {2013}, author = {Amirian, ES and Petrosino, JF and Ajami, NJ and Liu, Y and Mims, MP and Scheurer, ME}, title = {Potential role of gastrointestinal microbiota composition in prostate cancer risk.}, journal = {Infectious agents and cancer}, volume = {8}, number = {1}, pages = {42}, pmid = {24180596}, issn = {1750-9378}, abstract = {BACKGROUND: Among men in the U.S., prostate cancer is the most common cancer and the second leading cause of cancer death. Despite its prevalence, there are few established risk factors for prostate cancer. Some studies have found that intake of certain foods/nutrients may be associated with prostate cancer risk, but few have accounted for how intake and metabolic factors may interact to influence bioavailable nutrient levels and subsequent disease risk.<br><br>The composition of the gastrointestinal (GI) microbiome may influence metabolism of dietary compounds and nutrients (e.g., plant phenols, calcium, choline) that may be relevant to prostate cancer risk. We, therefore, propose the hypothesis that GI microbiota may have a markedly different composition among individuals with higher prostate cancer risk. These individuals could have microbial profiles that are conducive to intestinal inflammation and/or are less favorable for the metabolism and uptake of chemopreventive agents.<br><br>TESTING THE HYPOTHESIS: Because very little preliminary data exist on this potential association, a case-control study may provide valuable information on this topic. Such a study could evaluate whether the GI microbial profile is markedly different between three groups of individuals: healthy men, those with latent prostate cancer, and those with invasive prostate cancer. Any findings could then be validated in a larger study, designed to collect a series of specimens over time.<br><br>Given the plethora of information emerging from the Human Microbiome Project, this is an opportune time to explore associations between the microbiome and complex human diseases. Identification of profiles that alter the host's risk for disease may clarify inconsistencies in the literature on dietary factors and cancer risk, and could provide valuable targets for novel cancer prevention strategies.}, }
@article {pmid24178066, year = {2014}, author = {Hong, P and Liu, CM and Nordstrom, L and Lalwani, AK}, title = {The role of the human microbiome in otolaryngology-head and neck surgery: a contemporary review.}, journal = {The Laryngoscope}, volume = {124}, number = {6}, pages = {1352-1357}, pmid = {24178066}, issn = {1531-4995}, support = {R15 DE021194/DE/NIDCR NIH HHS/United States ; 1R15DE021194-01/DE/NIDCR NIH HHS/United States ; }, mesh = {Female ; Head/microbiology/surgery ; Humans ; Male ; *Microbiota ; Neck/microbiology/surgery ; Otorhinolaryngologic Diseases/*microbiology/*surgery ; Otorhinolaryngologic Surgical Procedures/*methods ; Risk Assessment ; Sensitivity and Specificity ; Treatment Outcome ; }, abstract = {OBJECTIVES/HYPOTHESIS: The human microbiome represents the collective genomes and gene products of microbes living within and on humans. The objective of this review is to provide a summary of the current microbiome literature pertaining to otolaryngology-head and neck surgery.<br><br>DATA SOURCE: Ovid MEDLINE.<br><br>METHODS: Scientific publications with clinical correlates.<br><br>RESULTS: Human microbiome studies have been facilitated by culture-independent, high-throughput sequencing methods. Data from the Human Microbiome Project has shown that the composition of the human microbiome is specific to each body site and that each individual has a unique microbiome. Alterations in the human microbiome are associated with some disease states; thus, novel therapeutic strategies are being developed based on concepts and findings stemming from microbiome research.<br><br>CONCLUSIONS: Although a growing body of research shows potential significance of the human microbiome for human health and disease, there is a paucity of microbiome studies in otolaryngology. More studies are required to increase our understanding of the indigenous microbiota and their effects on diseases of the head and neck.}, }
@article {pmid24160697, year = {2014}, author = {Mani, S and Boelsterli, UA and Redinbo, MR}, title = {Understanding and modulating mammalian-microbial communication for improved human health.}, journal = {Annual review of pharmacology and toxicology}, volume = {54}, number = {}, pages = {559-580}, pmid = {24160697}, issn = {1545-4304}, support = {CA161879/CA/NCI NIH HHS/United States ; R01 CA161879/CA/NCI NIH HHS/United States ; CA98468/CA/NCI NIH HHS/United States ; R01 CA098468/CA/NCI NIH HHS/United States ; R01 CA127231/CA/NCI NIH HHS/United States ; CA127231/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Anti-Inflammatory Agents/pharmacology ; Camptothecin/administration &amp; dosage/adverse effects/analogs &amp; derivatives ; Disease Models, Animal ; Enteritis/chemically induced/drug therapy ; Eosinophilia/chemically induced/drug therapy ; Gastritis/chemically induced/drug therapy ; Gastrointestinal Tract/*drug effects/*microbiology ; Glucuronidase/pharmacology ; Humans ; Irinotecan ; Lipopolysaccharides/pharmacology ; *Mammals ; Microbiota/*drug effects ; }, abstract = {The fact that the bacteria in the human gastrointestinal (GI) tract play a symbiotic role was noted as early as 1885, well before we began to manage microbial infections using antibiotics. However, even with the first antimicrobial compounds used in humans, the sulfa drugs, microbes were recognized to be critically involved in the biotransformation of these therapeutics. Thus, the roles played by the microbiota in physiology and in the management of human health have long been appreciated. Detailed examinations of GI symbiotic bacteria that started in the early 2000s and the first phases of the Human Microbiome Project that were completed in 2012 have ushered in an exciting period of granularity with respect to the ecology, genetics, and chemistry of the mammalian-microbial axes of communication. Here we review aspects of the biochemical pathways at play between commensal GI bacteria and several mammalian systems, including both local-epithelia and nonlocal responses impacting inflammation, immunology, metabolism, and neurobiology. Finally, we discuss how the microbial biotransformation of therapeutic compounds, such as anticancer or nonsteroidal anti-inflammatory drugs, can be modulated to reduce toxicity and potentially improve therapeutic efficacy.}, }
@article {pmid24159534, year = {2013}, author = {Shin, HH and Cho, SH}, title = {Prevalence of Antimicrobial Resistance in Escherichia coli Strains Isolated from Fishery Workers.}, journal = {Osong public health and research perspectives}, volume = {4}, number = {2}, pages = {72-75}, pmid = {24159534}, issn = {2210-9099}, abstract = {OBJECTIVES: This study aimed to characterize the prevalence of antibiotic resistance in Escherichia coli isolates from the fecal samples of fishery workers who work in fish farms and often use antibiotics for the feeding fishes.<br><br>METHODS: Seventy-three E. coli strains isolated from the fecal samples of fishery workers and 180 isolates from a control group of restaurant workers were tested for antibiotic resistance by agar disk diffusion with 16 antimicrobial agents.<br><br>RESULTS: About 30% of isolates from each group showed antimicrobial resistance to ampicillin, and 60% of isolates from fishery workers and 41% from restaurant workers were resistant to tetracycline. The isolates showed higher resistance to cephalothin and cefoxitin than to other cephem antibiotics and to gentamicin than to other aminogycosides. Our data indicated that fecal E. coli isolates from fishery workers showed higher antibiotic resistance than those of non-fishery workers (restaurant workers), especially to cephalothin, tetracycline, and trimethoprim-sulfamethoxazole (p < 0.05). However, rates of multidrug resistance were similar among the fishery workers and restaurant workers.<br><br>CONCLUSION: Frequent use of antibiotics may cause increased antibiotic resistance in the human microbiome.}, }
@article {pmid24146609, year = {2013}, author = {Carr, R and Shen-Orr, SS and Borenstein, E}, title = {Reconstructing the genomic content of microbiome taxa through shotgun metagenomic deconvolution.}, journal = {PLoS computational biology}, volume = {9}, number = {10}, pages = {e1003292}, pmid = {24146609}, issn = {1553-7358}, support = {DP2 AT007802/AT/NCCIH NIH HHS/United States ; U19 AI057229/AI/NIAID NIH HHS/United States ; DP2AT00780201/AT/NCCIH NIH HHS/United States ; }, mesh = {Genome, Bacterial/*genetics ; Humans ; Metagenomics/*methods ; Microbiota/*genetics ; Models, Genetic ; Sequence Analysis, DNA/*methods ; Tongue/microbiology ; }, abstract = {Metagenomics has transformed our understanding of the microbial world, allowing researchers to bypass the need to isolate and culture individual taxa and to directly characterize both the taxonomic and gene compositions of environmental samples. However, associating the genes found in a metagenomic sample with the specific taxa of origin remains a critical challenge. Existing binning methods, based on nucleotide composition or alignment to reference genomes allow only a coarse-grained classification and rely heavily on the availability of sequenced genomes from closely related taxa. Here, we introduce a novel computational framework, integrating variation in gene abundances across multiple samples with taxonomic abundance data to deconvolve metagenomic samples into taxa-specific gene profiles and to reconstruct the genomic content of community members. This assembly-free method is not bounded by various factors limiting previously described methods of metagenomic binning or metagenomic assembly and represents a fundamentally different approach to metagenomic-based genome reconstruction. An implementation of this framework is available at http://elbo.gs.washington.edu/software.html. We first describe the mathematical foundations of our framework and discuss considerations for implementing its various components. We demonstrate the ability of this framework to accurately deconvolve a set of metagenomic samples and to recover the gene content of individual taxa using synthetic metagenomic samples. We specifically characterize determinants of prediction accuracy and examine the impact of annotation errors on the reconstructed genomes. We finally apply metagenomic deconvolution to samples from the Human Microbiome Project, successfully reconstructing genus-level genomic content of various microbial genera, based solely on variation in gene count. These reconstructed genera are shown to correctly capture genus-specific properties. With the accumulation of metagenomic data, this deconvolution framework provides an essential tool for characterizing microbial taxa never before seen, laying the foundation for addressing fundamental questions concerning the taxa comprising diverse microbial communities.}, }
@article {pmid24136997, year = {2014}, author = {Markowitz, VM and Chen, IM and Chu, K and Szeto, E and Palaniappan, K and Pillay, M and Ratner, A and Huang, J and Pagani, I and Tringe, S and Huntemann, M and Billis, K and Varghese, N and Tennessen, K and Mavromatis, K and Pati, A and Ivanova, NN and Kyrpides, NC}, title = {IMG/M 4 version of the integrated metagenome comparative analysis system.}, journal = {Nucleic acids research}, volume = {42}, number = {Database issue}, pages = {D568-73}, pmid = {24136997}, issn = {1362-4962}, support = {U01-HG004866/HG/NHGRI NIH HHS/United States ; }, mesh = {*Databases, Genetic ; Gene Expression Profiling ; Genome, Archaeal ; Genome, Bacterial ; Genome, Viral ; Internet ; *Metagenome ; Metagenomics/standards ; Plasmids/genetics ; Reference Standards ; Sequence Analysis, Protein ; Software ; Systems Integration ; }, abstract = {IMG/M (http://img.jgi.doe.gov/m) provides support for comparative analysis of microbial community aggregate genomes (metagenomes) in the context of a comprehensive set of reference genomes from all three domains of life, as well as plasmids, viruses and genome fragments. IMG/M's data content and analytical tools have expanded continuously since its first version was released in 2007. Since the last report published in the 2012 NAR Database Issue, IMG/M's database architecture, annotation and data integration pipelines and analysis tools have been extended to copewith the rapid growth in the number and size of metagenome data sets handled by the system. IMG/M data marts provide support for the analysis of publicly available genomes, expert review of metagenome annotations (IMG/M ER: http://img.jgi.doe.gov/mer) and Human Microbiome Project (HMP)-specific metagenome samples (IMG/M HMP: http://img.jgi.doe.gov/imgm_hmp).}, }
@article {pmid24128059, year = {2013}, author = {Xia, F and Chen, J and Fung, WK and Li, H}, title = {A logistic normal multinomial regression model for microbiome compositional data analysis.}, journal = {Biometrics}, volume = {69}, number = {4}, pages = {1053-1063}, doi = {10.1111/biom.12079}, pmid = {24128059}, issn = {1541-0420}, support = {CA127334/CA/NCI NIH HHS/United States ; GM097505/GM/NIGMS NIH HHS/United States ; }, mesh = {Bacteria/classification/*genetics/*isolation &amp; purification ; Computer Simulation ; *Data Interpretation, Statistical ; Humans ; Intestines/*microbiology ; *Logistic Models ; Microbiota/*genetics ; *Regression Analysis ; }, abstract = {Changes in human microbiome are associated with many human diseases. Next generation sequencing technologies make it possible to quantify the microbial composition without the need for laboratory cultivation. One important problem of microbiome data analysis is to identify the environmental/biological covariates that are associated with different bacterial taxa. Taxa count data in microbiome studies are often over-dispersed and include many zeros. To account for such an over-dispersion, we propose to use an additive logistic normal multinomial regression model to associate the covariates to bacterial composition. The model can naturally account for sampling variabilities and zero observations and also allow for a flexible covariance structure among the bacterial taxa. In order to select the relevant covariates and to estimate the corresponding regression coefficients, we propose a group ℓ1 penalized likelihood estimation method for variable selection and estimation. We develop a Monte Carlo expectation-maximization algorithm to implement the penalized likelihood estimation. Our simulation results show that the proposed method outperforms the group ℓ1 penalized multinomial logistic regression and the Dirichlet multinomial regression models in variable selection. We demonstrate the methods using a data set that links human gut microbiome to micro-nutrients in order to identify the nutrients that are associated with the human gut microbiome enterotype.}, }
@article {pmid24123819, year = {2013}, author = {Hemarajata, P and Gao, C and Pflughoeft, KJ and Thomas, CM and Saulnier, DM and Spinler, JK and Versalovic, J}, title = {Lactobacillus reuteri-specific immunoregulatory gene rsiR modulates histamine production and immunomodulation by Lactobacillus reuteri.}, journal = {Journal of bacteriology}, volume = {195}, number = {24}, pages = {5567-5576}, pmid = {24123819}, issn = {1098-5530}, support = {UH3 DK083990/DK/NIDDK NIH HHS/United States ; R01 DK065075/DK/NIDDK NIH HHS/United States ; P30 DK056338/DK/NIDDK NIH HHS/United States ; DK56338/DK/NIDDK NIH HHS/United States ; R01 AT004326/AT/NCCIH NIH HHS/United States ; }, mesh = {Animals ; Artificial Gene Fusion ; Colitis/chemically induced/microbiology/pathology ; Cytokines/*antagonists &amp; inhibitors ; Disease Models, Animal ; *Gene Expression Regulation, Bacterial ; Genes, Reporter ; Histamine/*metabolism ; Humans ; *Immunomodulation ; Limosilactobacillus reuteri/genetics/*immunology/isolation &amp; purification/metabolism ; Mice ; Microbiota ; Promoter Regions, Genetic ; Transcription Factors/*metabolism ; Transcription, Genetic ; Trinitrobenzenesulfonic Acid/toxicity ; }, abstract = {Human microbiome-derived strains of Lactobacillus reuteri potently suppress proinflammatory cytokines like human tumor necrosis factor (TNF) by converting the amino acid l-histidine to the biogenic amine histamine. Histamine suppresses mitogen-activated protein (MAP) kinase activation and cytokine production by signaling via histamine receptor type 2 (H2) on myeloid cells. Investigations of the gene expression profiles of immunomodulatory L. reuteri ATCC PTA 6475 highlighted numerous genes that were highly expressed during the stationary phase of growth, when TNF suppression is most potent. One such gene was found to be a regulator of genes involved in histidine-histamine metabolism by this probiotic species. During the course of these studies, this gene was renamed the Lactobacillus reuteri-specific immunoregulatory (rsiR) gene. The rsiR gene is essential for human TNF suppression by L. reuteri and expression of the histidine decarboxylase (hdc) gene cluster on the L. reuteri chromosome. Inactivation of rsiR resulted in diminished TNF suppression in vitro and reduced anti-inflammatory effects in vivo in a trinitrobenzene sulfonic acid (TNBS)-induced mouse model of acute colitis. A L. reuteri strain lacking an intact rsiR gene was unable to suppress colitis and resulted in greater concentrations of serum amyloid A (SAA) in the bloodstream of affected animals. The PhdcAB promoter region targeted by rsiR was defined by reporter gene experiments. These studies support the presence of a regulatory gene, rsiR, which modulates the expression of a gene cluster known to mediate immunoregulation by probiotics at the transcriptional level. These findings may point the way toward new strategies for controlling gene expression in probiotics by dietary interventions or microbiome manipulation.}, }
@article {pmid24123672, year = {2014}, author = {Rodriguez-R, LM and Konstantinidis, KT}, title = {Nonpareil: a redundancy-based approach to assess the level of coverage in metagenomic datasets.}, journal = {Bioinformatics (Oxford, England)}, volume = {30}, number = {5}, pages = {629-635}, doi = {10.1093/bioinformatics/btt584}, pmid = {24123672}, issn = {1367-4811}, mesh = {Algorithms ; Metagenome ; Metagenomics/*methods ; Microbiota ; Soil Microbiology ; }, abstract = {MOTIVATION: Determining the fraction of the diversity within a microbial community sampled and the amount of sequencing required to cover the total diversity represent challenging issues for metagenomics studies. Owing to these limitations, central ecological questions with respect to the global distribution of microbes and the functional diversity of their communities cannot be robustly assessed.<br><br>RESULTS: We introduce Nonpareil, a method to estimate and project coverage in metagenomes. Nonpareil does not rely on high-quality assemblies, operational taxonomic unit calling or comprehensive reference databases; thus, it is broadly applicable to metagenomic studies. Application of Nonpareil on available metagenomic datasets provided estimates on the relative complexity of soil, freshwater and human microbiome communities, and suggested that &#x223c;200 Gb of sequencing data are required for 95% abundance-weighted average coverage of the soil communities analyzed.<br><br>Nonpareil is available at https://github.com/lmrodriguezr/nonpareil/ under the Artistic License 2.0.}, }
@article {pmid24118234, year = {2013}, author = {Bisgaard, H and Vissing, NH and Carson, CG and Bischoff, AL and Følsgaard, NV and Kreiner-Møller, E and Chawes, BL and Stokholm, J and Pedersen, L and Bjarnadóttir, E and Thysen, AH and Nilsson, E and Mortensen, LJ and Olsen, SF and Schjørring, S and Krogfelt, KA and Lauritzen, L and Brix, S and Bønnelykke, K}, title = {Deep phenotyping of the unselected COPSAC2010 birth cohort study.}, journal = {Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology}, volume = {43}, number = {12}, pages = {1384-1394}, pmid = {24118234}, issn = {1365-2222}, mesh = {Adult ; Asthma/etiology ; Child ; Child, Preschool ; Cohort Studies ; Denmark ; Dietary Supplements ; Eczema/*etiology/prevention &amp; control ; Female ; Fish Oils/administration &amp; dosage ; Humans ; Hypersensitivity/*etiology/prevention &amp; control ; Infant ; Infant, Newborn ; Influenza Vaccines/administration &amp; dosage/immunology ; Longitudinal Studies ; Male ; Maternal Exposure ; *Phenotype ; Pregnancy ; Prenatal Exposure Delayed Effects ; Risk Factors ; Surveys and Questionnaires ; Vitamin D/administration &amp; dosage ; }, abstract = {BACKGROUND: We hypothesize that perinatal exposures, in particular the human microbiome and maternal nutrition during pregnancy, interact with the genetic predisposition to cause an abnormal immune modulation in early life towards a trajectory to chronic inflammatory diseases such as asthma and others.<br><br>OBJECTIVE: The aim of this study is to explore these interactions by conducting a longitudinal study in an unselected cohort of pregnant women and their offspring with emphasis on deep clinical phenotyping, exposure assessment, and biobanking. Exposure assessments focus on the human microbiome. Nutritional intervention during pregnancy in randomized controlled trials are included in the study to prevent disease and to be able to establish causal relationships.<br><br>METHODS: Pregnant women from eastern Denmark were invited during 2008-2010 to a novel unselected 'COPSAC2010 ' cohort. The women visited the clinic during pregnancy weeks 24 and 36. Their children were followed at the clinic with deep phenotyping and collection of biological samples at nine regular visits until the age of 3 and at acute symptoms. Randomized controlled trials of high-dose vitamin D and fish oil supplements were conducted during pregnancy, and a trial of azithromycin for acute lung symptoms was conducted in the children with recurrent wheeze.<br><br>RESULTS: Seven hundred and thirty-eight mothers were recruited from week 24 of gestation, and 700 of their children were included in the birth cohort. The cohort has an over-representation of atopic parents. The participant satisfaction was high and the adherence equally high with 685 children (98%) attending the 1 year clinic visit and 667 children (95%) attending the 2 year clinic visit.<br><br>CONCLUSIONS: The COPSAC2010 birth cohort study provides longitudinal clinical follow-up with highly specific end-points, exposure assessments, and biobanking. The cohort has a high adherence rate promising strong data to elucidate the interaction between genomics and the exposome in perinatal life leading to lifestyle-related chronic inflammatory disorders such as asthma.}, }
@article {pmid24107500, year = {2013}, author = {Szajewska, H}, title = {Microbiota modulation: can probiotics prevent/treat disease in pediatrics?.}, journal = {Nestle Nutrition Institute workshop series}, volume = {77}, number = {}, pages = {99-110}, doi = {10.1159/000351392}, pmid = {24107500}, issn = {1664-2155}, mesh = {*Bacteria ; Chronic Disease/*therapy ; Gastrointestinal Diseases/*therapy ; Humans ; *Microbiota ; *Pediatrics ; Probiotics/*therapeutic use ; Respiratory Tract Infections/*therapy ; }, abstract = {A number of metagenomic analyses providing knowledge of the human microbiome have yielded data on the differences between healthy and diseased individuals. Microbiota manipulation, such as through the administration of probiotics, may potentially contribute to improved health outcomes. The objective of this review was to summarize the most recent data on the use of probiotics to treat or prevent diseases in pediatrics. MEDLINE and The Cochrane Database of Systematic Reviews were searched in September 2012 for randomized controlled trials or their meta-analyses published in the last 3 years. To provide examples of current research interests, the focus of the search was on well-studied, common pediatric conditions as well as on some chronic diseases for which the benefits of gut microbiota manipulation are only in the early stages.}, }
@article {pmid24065795, year = {2013}, author = {Karlsson, F and Tremaroli, V and Nielsen, J and Bäckhed, F}, title = {Assessing the human gut microbiota in metabolic diseases.}, journal = {Diabetes}, volume = {62}, number = {10}, pages = {3341-3349}, pmid = {24065795}, issn = {1939-327X}, mesh = {Animals ; Atherosclerosis/genetics/metabolism/*microbiology ; Diabetes Mellitus, Type 1/genetics/metabolism/*microbiology ; Diabetes Mellitus, Type 2/genetics/metabolism/*microbiology ; Diet ; Disease Models, Animal ; Female ; Gastrointestinal Tract/metabolism/*microbiology ; Genetic Variation ; *Germ-Free Life ; Humans ; Male ; Mice ; *Microbiota/genetics/physiology ; Obesity/genetics/metabolism/*microbiology ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, RNA/methods ; }, abstract = {Recent findings have demonstrated that the gut microbiome complements our human genome with at least 100-fold more genes. In contrast to our Homo sapiens-derived genes, the microbiome is much more plastic, and its composition changes with age and diet, among other factors. An altered gut microbiota has been associated with several diseases, including obesity and diabetes, but the mechanisms involved remain elusive. Here we discuss factors that affect the gut microbiome, how the gut microbiome may contribute to metabolic diseases, and how to study the gut microbiome. Next-generation sequencing and development of software packages have led to the development of large-scale sequencing efforts to catalog the human microbiome. Furthermore, the use of genetically engineered gnotobiotic mouse models may increase our understanding of mechanisms by which the gut microbiome modulates host metabolism. A combination of classical microbiology, sequencing, and animal experiments may provide further insights into how the gut microbiota affect host metabolism and physiology.}, }
@article {pmid24060131, year = {2013}, author = {Navas-Molina, JA and Peralta-Sánchez, JM and González, A and McMurdie, PJ and Vázquez-Baeza, Y and Xu, Z and Ursell, LK and Lauber, C and Zhou, H and Song, SJ and Huntley, J and Ackermann, GL and Berg-Lyons, D and Holmes, S and Caporaso, JG and Knight, R}, title = {Advancing our understanding of the human microbiome using QIIME.}, journal = {Methods in enzymology}, volume = {531}, number = {}, pages = {371-444}, pmid = {24060131}, issn = {1557-7988}, support = {R01 GM086884/GM/NIGMS NIH HHS/United States ; T32 GM008759/GM/NIGMS NIH HHS/United States ; T32 GM142607/GM/NIGMS NIH HHS/United States ; R01GM086884/GM/NIGMS NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Animals ; Bacteria/*genetics/pathogenicity ; Computational Biology ; High-Throughput Nucleotide Sequencing/*methods ; Humans ; Mice ; Microbiota/*genetics ; Phylogeny ; Software ; }, abstract = {High-throughput DNA sequencing technologies, coupled with advanced bioinformatics tools, have enabled rapid advances in microbial ecology and our understanding of the human microbiome. QIIME (Quantitative Insights Into Microbial Ecology) is an open-source bioinformatics software package designed for microbial community analysis based on DNA sequence data, which provides a single analysis framework for analysis of raw sequence data through publication-quality statistical analyses and interactive visualizations. In this chapter, we demonstrate the use of the QIIME pipeline to analyze microbial communities obtained from several sites on the bodies of transgenic and wild-type mice, as assessed using 16S rRNA gene sequences generated on the Illumina MiSeq platform. We present our recommended pipeline for performing microbial community analysis and provide guidelines for making critical choices in the process. We present examples of some of the types of analyses that are enabled by QIIME and discuss how other tools, such as phyloseq and R, can be applied to expand upon these analyses.}, }
@article {pmid24058885, year = {2013}, author = {McCoy, CO and Matsen, FA}, title = {Abundance-weighted phylogenetic diversity measures distinguish microbial community states and are robust to sampling depth.}, journal = {PeerJ}, volume = {1}, number = {}, pages = {e157}, pmid = {24058885}, issn = {2167-8359}, support = {R37 AI038518/AI/NIAID NIH HHS/United States ; }, abstract = {In microbial ecology studies, the most commonly used ways of investigating alpha (within-sample) diversity are either to apply non-phylogenetic measures such as Simpson's index to Operational Taxonomic Unit (OTU) groupings, or to use classical phylogenetic diversity (PD), which is not abundance-weighted. Although alpha diversity measures that use abundance information in a phylogenetic framework do exist, they are not widely used within the microbial ecology community. The performance of abundance-weighted phylogenetic diversity measures compared to classical discrete measures has not been explored, and the behavior of these measures under rarefaction (sub-sampling) is not yet clear. In this paper we compare the ability of various alpha diversity measures to distinguish between different community states in the human microbiome for three different datasets. We also present and compare a novel one-parameter family of alpha diversity measures, BWPDθ, that interpolates between classical phylogenetic diversity (PD) and an abundance-weighted extension of PD. Additionally, we examine the sensitivity of these phylogenetic diversity measures to sampling, via computational experiments and by deriving a closed form solution for the expectation of phylogenetic quadratic entropy under re-sampling. On the three datasets, a phylogenetic measure always performed best, and two abundance-weighted phylogenetic diversity measures were the only measures ranking in the top four across all datasets. OTU-based measures, on the other hand, are less effective in distinguishing community types. In addition, abundance-weighted phylogenetic diversity measures are less sensitive to differing sampling intensity than their unweighted counterparts. Based on these results we encourage the use of abundance-weighted phylogenetic diversity measures, especially for cases such as microbial ecology where species delimitation is difficult.}, }
@article {pmid24058058, year = {2013}, author = {Nijkamp, JF and Pop, M and Reinders, MJ and de Ridder, D}, title = {Exploring variation-aware contig graphs for (comparative) metagenomics using MaryGold.}, journal = {Bioinformatics (Oxford, England)}, volume = {29}, number = {22}, pages = {2826-2834}, pmid = {24058058}, issn = {1367-4811}, support = {R01 AI100947/AI/NIAID NIH HHS/United States ; }, mesh = {*Algorithms ; Alleles ; *Contig Mapping ; *Genetic Variation ; Humans ; Infant ; Metagenome ; Metagenomics/*methods ; Software ; }, abstract = {MOTIVATION: Although many tools are available to study variation and its impact in single genomes, there is a lack of algorithms for finding such variation in metagenomes. This hampers the interpretation of metagenomics sequencing datasets, which are increasingly acquired in research on the (human) microbiome, in environmental studies and in the study of processes in the production of foods and beverages. Existing algorithms often depend on the use of reference genomes, which pose a problem when a metagenome of a priori unknown strain composition is studied. In this article, we develop a method to perform reference-free detection and visual exploration of genomic variation, both within a single metagenome and between metagenomes.<br><br>RESULTS: We present the MaryGold algorithm and its implementation, which efficiently detects bubble structures in contig graphs using graph decomposition. These bubbles represent variable genomic regions in closely related strains in metagenomic samples. The variation found is presented in a condensed Circos-based visualization, which allows for easy exploration and interpretation of the found variation. We validated the algorithm on two simulated datasets containing three respectively seven Escherichia coli genomes and showed that finding allelic variation in these genomes improves assemblies. Additionally, we applied MaryGold to publicly available real metagenomic datasets, enabling us to find within-sample genomic variation in the metagenomes of a kimchi fermentation process, the microbiome of a premature infant and in microbial communities living on acid mine drainage. Moreover, we used MaryGold for between-sample variation detection and exploration by comparing sequencing data sampled at different time points for both of these datasets.<br><br>AVAILABILITY: MaryGold has been written in C++ and Python and can be downloaded from http://bioinformatics.tudelft.nl/software}, }
@article {pmid24023808, year = {2013}, author = {Ross, EM and Moate, PJ and Marett, LC and Cocks, BG and Hayes, BJ}, title = {Metagenomic predictions: from microbiome to complex health and environmental phenotypes in humans and cattle.}, journal = {PloS one}, volume = {8}, number = {9}, pages = {e73056}, pmid = {24023808}, issn = {1932-6203}, mesh = {Animals ; Cattle ; *Environment ; *Health ; Humans ; Inflammatory Bowel Diseases/genetics/microbiology ; *Metagenomics ; Methane/biosynthesis ; Microbiota/*genetics ; *Phenotype ; }, abstract = {Mammals have a large cohort of endo- and ecto- symbiotic microorganisms (the microbiome) that potentially influence host phenotypes. There have been numerous exploratory studies of these symbiotic organisms in humans and other animals, often with the aim of relating the microbiome to a complex phenotype such as body mass index (BMI) or disease state. Here, we describe an efficient methodology for predicting complex traits from quantitative microbiome profiles. The method was demonstrated by predicting inflammatory bowel disease (IBD) status and BMI from human microbiome data, and enteric greenhouse gas production from dairy cattle rumen microbiome profiles. The method uses unassembled massively parallel sequencing (MPS) data to form metagenomic relationship matrices (analogous to genomic relationship matrices used in genomic predictions) to predict IBD, BMI and methane production phenotypes with useful accuracies (r = 0.423, 0.422 and 0.466 respectively). Our results show that microbiome profiles derived from MPS can be used to predict complex phenotypes of the host. Although the number of biological replicates used here limits the accuracy that can be achieved, preliminary results suggest this approach may surpass current prediction accuracies that are based on the host genome. This is especially likely for traits that are largely influenced by the gut microbiota, for example digestive tract disorders or metabolic functions such as enteric methane production in cattle.}, }
@article {pmid24021386, year = {2013}, author = {Robertson, CE and Harris, JK and Wagner, BD and Granger, D and Browne, K and Tatem, B and Feazel, LM and Park, K and Pace, NR and Frank, DN}, title = {Explicet: graphical user interface software for metadata-driven management, analysis and visualization of microbiome data.}, journal = {Bioinformatics (Oxford, England)}, volume = {29}, number = {23}, pages = {3100-3101}, pmid = {24021386}, issn = {1367-4811}, support = {R21 HG005964/HG/NHGRI NIH HHS/United States ; HG005964/HG/NHGRI NIH HHS/United States ; }, mesh = {Computational Biology ; *Computer Graphics ; *Database Management Systems ; High-Throughput Nucleotide Sequencing ; Humans ; Metagenome ; Microbiota/*genetics ; Sequence Analysis, DNA ; *Software ; *User-Computer Interface ; }, abstract = {Studies of the human microbiome, and microbial community ecology in general, have blossomed of late and are now a burgeoning source of exciting research findings. Along with the advent of next-generation sequencing platforms, which have dramatically increased the scope of microbiome-related projects, several high-performance sequence analysis pipelines (e.g. QIIME, MOTHUR, VAMPS) are now available to investigators for microbiome analysis. The subject of our manuscript, the graphical user interface-based Explicet software package, fills a previously unmet need for a robust, yet intuitive means of integrating the outputs of the software pipelines with user-specified metadata and then visualizing the combined data.}, }
@article {pmid24010110, year = {2013}, author = {Kim, BS and Jeon, YS and Chun, J}, title = {Current status and future promise of the human microbiome.}, journal = {Pediatric gastroenterology, hepatology &amp; nutrition}, volume = {16}, number = {2}, pages = {71-79}, pmid = {24010110}, issn = {2234-8646}, abstract = {The human-associated microbiota is diverse, varies between individuals and body sites, and is important in human health. Microbes in human body play an essential role in immunity, health, and disease. The human microbiome has been studies using the advances of next-generation sequencing and its metagenomic applications. This has allowed investigation of the microbial composition in the human body, and identification of the functional genes expressed by this microbial community. The gut microbes have been found to be the most diverse and constitute the densest cell number in the human microbiota; thus, it has been studied more than other sites. Early results have indicated that the imbalances in gut microbiota are related to numerous disorders, such as inflammatory bowel disease, colorectal cancer, diabetes, and atopy. Clinical therapy involving modulating of the microbiota, such as fecal transplantation, has been applied, and its effects investigated in some diseases. Human microbiome studies form part of human genome projects, and understanding gleaned from studies increase the possibility of various applications including personalized medicine.}, }
@article {pmid23997353, year = {2012}, author = {Khurana, S}, title = {Human microbiome and cancer: an insight.}, journal = {Indian journal of microbiology}, volume = {52}, number = {3}, pages = {519-520}, pmid = {23997353}, issn = {0046-8991}, }
@article {pmid23997318, year = {2012}, author = {Rup, L}, title = {The human microbiome project.}, journal = {Indian journal of microbiology}, volume = {52}, number = {3}, pages = {315}, doi = {10.1007/s12088-012-0304-9}, pmid = {23997318}, issn = {0046-8991}, }
@article {pmid23978655, year = {2014}, author = {Balhara, M and Ruhil, S and Kumar, M and Dhankhar, S and Chhillar, AK}, title = {Inhibition of conidiophore development in Aspergillus fumigatus by an Escherichia coli DH5α strain, a promising antifungal candidate against aspergillosis.}, journal = {Journal de mycologie medicale}, volume = {24}, number = {1}, pages = {1-12}, doi = {10.1016/j.mycmed.2013.07.055}, pmid = {23978655}, issn = {1773-0449}, mesh = {Antifungal Agents/isolation &amp; purification/*pharmacology/therapeutic use ; Aspergillosis/prevention &amp; control ; Aspergillus fumigatus/*drug effects/physiology ; Down-Regulation/drug effects ; Escherichia coli/chemistry ; Escherichia coli Proteins/isolation &amp; purification/*pharmacology/therapeutic use ; Humans ; Microbial Sensitivity Tests ; Pilot Projects ; Spores, Fungal/*drug effects/growth &amp; development ; }, abstract = {The opportunistic human pathogen Aspergillus fumigatus produces a massive number of asexual spores (conidia) as the primary means of dispersal, survival, genome protection and infection of hosts. In this report, we investigated secretory and cytosolic proteins of non-pathogenic bacterial species (mostly belonging to human microbiome) for antifungal potential against A. fumigatus, A. flavus and A. niger. Our preliminary results revealed that cytosolic proteins of E. coli DH5α were most active and the less toxic against various pathogenic isolates of A. fumigatus (the major pathogenic species), depicting a minimum inhibitory concentration (MIC) of 62.50 μg/mL, 62.50 μg/mL and 12.50 μg/disc using microbroth dilution assay (MDA), percentage spore germination inhibition assay (PSGI) and disc diffusion assay (DDA), respectively. E. coli protein was non-toxic against human erythrocytes at doses up to 1000 μg/mL as compared to standard drug, amphotericin B which lysed 100% of erythrocytes at a concentration of 37.50 μg/mL. Time kill analysis proved it to be fungicidal in a concentration and time-dependent manner. Scanning electron microscopic studies (SEM) were carried out to prevail what kind of damage it causes to A. fumigatus. SEM results reported that conidiophore (structures forming conidia) development was halted as a major consequence, reducing the number of conidiophores to insignificant values as well as alteration in their morphological attributes. This feature may contribute to the development of new prevention strategies against Aspergillus infections. Hyphal atrophy was also observed, evidenced by shrinking and flattening of hyphal walls and reduced, abrupt hyphal branching. Such actions may effectively reduce the invasive ability of Aspergillus as well as it can sterilize the fungal burden by obstructing the conidiation pathway of A. fumigatus. Hence, E. coli DH5α, being a commensal species, can lead to the development of antifungal molecule with novel targets in fungal metabolism, which will help in combating the antifungal resistance and toxicity associated with current therapy.}, }
@article {pmid23977672, year = {2013}, author = {Arnold, C}, title = {The pros and cons of probiotics.}, journal = {The Lancet. Infectious diseases}, volume = {13}, number = {7}, pages = {571-572}, doi = {10.1016/s1473-3099(13)70172-5}, pmid = {23977672}, issn = {1474-4457}, mesh = {Bacteria/*immunology/*metabolism ; Clinical Trials as Topic ; Diet/*methods ; *Drug Approval ; Humans ; Probiotics/administration &amp; dosage/*adverse effects/*pharmacology ; }, abstract = {Research into the human microbiome has encouraged proliferation of probiotic foods and supplements. Although the health claims seem legit, Carrie Arnold finds not everyone is convinced.}, }
@article {pmid23975157, year = {2013}, author = {Langille, MG and Zaneveld, J and Caporaso, JG and McDonald, D and Knights, D and Reyes, JA and Clemente, JC and Burkepile, DE and Vega Thurber, RL and Knight, R and Beiko, RG and Huttenhower, C}, title = {Predictive functional profiling of microbial communities using 16S rRNA marker gene sequences.}, journal = {Nature biotechnology}, volume = {31}, number = {9}, pages = {814-821}, pmid = {23975157}, issn = {1546-1696}, support = {P01 DK078669/DK/NIDDK NIH HHS/United States ; T32 GM008759/GM/NIGMS NIH HHS/United States ; R01HG004872/HG/NHGRI NIH HHS/United States ; /CAPMC/CIHR/Canada ; U01HG004866/HG/NHGRI NIH HHS/United States ; T32 GM080177/GM/NIGMS NIH HHS/United States ; R01 HG004872/HG/NHGRI NIH HHS/United States ; 1R01HG005969/HG/NHGRI NIH HHS/United States ; R01 HG005969/HG/NHGRI NIH HHS/United States ; T32 GM142607/GM/NIGMS NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; U01 HG004866/HG/NHGRI NIH HHS/United States ; P01DK078669/DK/NIDDK NIH HHS/United States ; }, mesh = {Bacteria/classification/genetics ; Genes, Bacterial/genetics/physiology ; Genetic Markers/genetics ; High-Throughput Nucleotide Sequencing ; Humans ; Metagenomics/*methods ; Microbiota/genetics ; Phylogeny ; RNA, Ribosomal, 16S/*genetics ; Sequence Analysis, DNA/*methods ; }, abstract = {Profiling phylogenetic marker genes, such as the 16S rRNA gene, is a key tool for studies of microbial communities but does not provide direct evidence of a community's functional capabilities. Here we describe PICRUSt (phylogenetic investigation of communities by reconstruction of unobserved states), a computational approach to predict the functional composition of a metagenome using marker gene data and a database of reference genomes. PICRUSt uses an extended ancestral-state reconstruction algorithm to predict which gene families are present and then combines gene families to estimate the composite metagenome. Using 16S information, PICRUSt recaptures key findings from the Human Microbiome Project and accurately predicts the abundance of gene families in host-associated and environmental communities, with quantifiable uncertainty. Our results demonstrate that phylogeny and function are sufficiently linked that this 'predictive metagenomic' approach should provide useful insights into the thousands of uncultivated microbial communities for which only marker gene surveys are currently available.}, }
@article {pmid23955152, year = {2013}, author = {Lee, SM and Donaldson, GP and Mikulski, Z and Boyajian, S and Ley, K and Mazmanian, SK}, title = {Bacterial colonization factors control specificity and stability of the gut microbiota.}, journal = {Nature}, volume = {501}, number = {7467}, pages = {426-429}, pmid = {23955152}, issn = {1476-4687}, support = {GM007616/GM/NIGMS NIH HHS/United States ; T32 GM007616/GM/NIGMS NIH HHS/United States ; P01 DK091222/DK/NIDDK NIH HHS/United States ; R01 GM099535/GM/NIGMS NIH HHS/United States ; GM099535/GM/NIGMS NIH HHS/United States ; R21 DK083633/DK/NIDDK NIH HHS/United States ; DK078938/DK/NIDDK NIH HHS/United States ; R01 DK078938/DK/NIDDK NIH HHS/United States ; R56 DK078938/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Bacterial Proteins/genetics/metabolism ; Bacteroides/*classification/genetics/growth &amp; development/*physiology ; Bacteroides fragilis/genetics/growth &amp; development/metabolism ; Colon/microbiology ; Conserved Sequence/genetics ; Evolution, Molecular ; Female ; Gastrointestinal Tract/*microbiology ; Gene Deletion ; Genes, Bacterial/genetics ; Germ-Free Life ; Intestinal Mucosa/microbiology ; Male ; Metagenome/*physiology ; Mice ; Polysaccharides/metabolism ; Species Specificity ; Symbiosis/genetics ; }, abstract = {Mammals harbour a complex gut microbiome, comprising bacteria that confer immunological, metabolic and neurological benefits. Despite advances in sequence-based microbial profiling and myriad studies defining microbiome composition during health and disease, little is known about the molecular processes used by symbiotic bacteria to stably colonize the gastrointestinal tract. We sought to define how mammals assemble and maintain the Bacteroides, one of the most numerically prominent genera of the human microbiome. Here we find that, whereas the gut normally contains hundreds of bacterial species, germ-free mice mono-associated with a single Bacteroides species are resistant to colonization by the same, but not different, species. To identify bacterial mechanisms for species-specific saturable colonization, we devised an in vivo genetic screen and discovered a unique class of polysaccharide utilization loci that is conserved among intestinal Bacteroides. We named this genetic locus the commensal colonization factors (ccf). Deletion of the ccf genes in the model symbiont, Bacteroides fragilis, results in colonization defects in mice and reduced horizontal transmission. The ccf genes of B. fragilis are upregulated during gut colonization, preferentially at the colonic surface. When we visualize microbial biogeography within the colon, B. fragilis penetrates the colonic mucus and resides deep within crypt channels, whereas ccf mutants are defective in crypt association. Notably, the CCF system is required for B. fragilis colonization following microbiome disruption with Citrobacter rodentium infection or antibiotic treatment, suggesting that the niche within colonic crypts represents a reservoir for bacteria to maintain long-term colonization. These findings reveal that intestinal Bacteroides have evolved species-specific physical interactions with the host that mediate stable and resilient gut colonization, and the CCF system represents a novel molecular mechanism for symbiosis.}, }
@article {pmid23949665, year = {2013}, author = {Tickle, TL and Segata, N and Waldron, L and Weingart, U and Huttenhower, C}, title = {Two-stage microbial community experimental design.}, journal = {The ISME journal}, volume = {7}, number = {12}, pages = {2330-2339}, pmid = {23949665}, issn = {1751-7370}, support = {R01 HG005969/HG/NHGRI NIH HHS/United States ; }, mesh = {Bias ; Ecology/*methods/standards ; Humans ; Metagenomics ; Microbiological Techniques/*methods/standards ; RNA, Ribosomal, 16S/genetics ; Reproducibility of Results ; Research Design/*standards ; }, abstract = {Microbial community samples can be efficiently surveyed in high throughput by sequencing markers such as the 16S ribosomal RNA gene. Often, a collection of samples is then selected for subsequent metagenomic, metabolomic or other follow-up. Two-stage study design has long been used in ecology but has not yet been studied in-depth for high-throughput microbial community investigations. To avoid ad hoc sample selection, we developed and validated several purposive sample selection methods for two-stage studies (that is, biological criteria) targeting differing types of microbial communities. These methods select follow-up samples from large community surveys, with criteria including samples typical of the initially surveyed population, targeting specific microbial clades or rare species, maximizing diversity, representing extreme or deviant communities, or identifying communities distinct or discriminating among environment or host phenotypes. The accuracies of each sampling technique and their influences on the characteristics of the resulting selected microbial community were evaluated using both simulated and experimental data. Specifically, all criteria were able to identify samples whose properties were accurately retained in 318 paired 16S amplicon and whole-community metagenomic (follow-up) samples from the Human Microbiome Project. Some selection criteria resulted in follow-up samples that were strongly non-representative of the original survey population; diversity maximization particularly undersampled community configurations. Only selection of intentionally representative samples minimized differences in the selected sample set from the original microbial survey. An implementation is provided as the microPITA (Microbiomes: Picking Interesting Taxa for Analysis) software for two-stage study design of microbial communities.}, }
@article {pmid23945370, year = {2014}, author = {Chistoserdova, L}, title = {Is metagenomics resolving identification of functions in microbial communities?.}, journal = {Microbial biotechnology}, volume = {7}, number = {1}, pages = {1-4}, pmid = {23945370}, issn = {1751-7915}, mesh = {*Biota ; Computational Biology/methods/trends ; *Metagenome ; Metagenomics/*methods/trends ; }, abstract = {We are coming up on the tenth anniversary of the broad use of the method involving whole metagenome shotgun sequencing, referred to as metagenomics. The application of this approach has definitely revolutionized microbiology and the related fields, including the realization of the importance of the human microbiome. As such, metagenomics has already provided a novel outlook on the complexity and dynamics of microbial communities that are an important part of the biosphere of the planet. Accumulation of massive amounts of sequence data also caused a surge in the development of bioinformatics tools specially designed to provide pipelines for data analysis and visualization. However, a critical outlook into the field is required to appreciate what could be and what has currently been gained from the massive sequence databases that are being generated with ever-increasing speed.}, }
@article {pmid23943792, year = {2013}, author = {Cox, MJ and Cookson, WO and Moffatt, MF}, title = {Sequencing the human microbiome in health and disease.}, journal = {Human molecular genetics}, volume = {22}, number = {R1}, pages = {R88-94}, doi = {10.1093/hmg/ddt398}, pmid = {23943792}, issn = {1460-2083}, support = {097117//Wellcome Trust/United Kingdom ; G1000758/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Bacteria/classification/genetics/growth &amp; development ; Genome, Bacterial ; High-Throughput Nucleotide Sequencing/*methods ; Host-Pathogen Interactions ; Humans ; Metagenomics ; Microbiota/*genetics/physiology ; RNA, Bacterial/genetics ; RNA, Ribosomal, 16S/genetics ; }, abstract = {Molecular techniques have revolutionized the practice of standard microbiology. In particular, 16S rRNA sequencing, whole microbial genome sequencing and metagenomics are revealing the extraordinary diversity of microorganisms on Earth and their vast genetic and metabolic repertoire. The increase in length, accuracy and number of reads generated by high-throughput sequencing has coincided with a surge of interest in the human microbiota, the totality of bacteria associated with the human body, in both health and disease. Traditional views of host/pathogen interactions are being challenged as the human microbiota are being revealed to be important in normal immune system function, to diseases not previously thought to have a microbial component and to infectious diseases with unknown aetiology. In this review, we introduce the nature of the human microbiota and application of these three key sequencing techniques for its study, highlighting both advances and challenges in the field. We go on to discuss how further adoption of additional techniques, also originally developed in environmental microbiology, will allow the establishment of disease causality against a background of numerous, complex and interacting microorganisms within the human host.}, }
@article {pmid23922841, year = {2013}, author = {Parks, DH and Mankowski, T and Zangooei, S and Porter, MS and Armanini, DG and Baird, DJ and Langille, MG and Beiko, RG}, title = {GenGIS 2: geospatial analysis of traditional and genetic biodiversity, with new gradient algorithms and an extensible plugin framework.}, journal = {PloS one}, volume = {8}, number = {7}, pages = {e69885}, pmid = {23922841}, issn = {1932-6203}, support = {//Canadian Institutes of Health Research/Canada ; }, mesh = {*Algorithms ; Biodiversity ; Environmental Monitoring ; Humans ; }, abstract = {GenGIS is free and open source software designed to integrate biodiversity data with a digital map and information about geography and habitat. While originally developed with microbial community analyses and phylogeography in mind, GenGIS has been applied to a wide range of datasets. A key feature of GenGIS is the ability to test geographic axes that can correspond to routes of migration or gradients that influence community similarity. Here we introduce GenGIS version 2, which extends the linear gradient tests introduced in the first version to allow comprehensive testing of all possible linear geographic axes. GenGIS v2 also includes a new plugin framework that supports the development and use of graphically driven analysis packages: initial plugins include implementations of linear regression and the Mantel test, calculations of alpha-diversity (e.g., Shannon Index) for all samples, and geographic visualizations of dissimilarity matrices. We have also implemented a recently published method for biomonitoring reference condition analysis (RCA), which compares observed species richness and diversity to predicted values to determine whether a given site has been impacted. The newest version of GenGIS supports vector data in addition to raster files. We demonstrate the new features of GenGIS by performing a full gradient analysis of an Australian kangaroo apple data set, by using plugins and embedded statistical commands to analyze human microbiome sample data, and by applying RCA to a set of samples from Atlantic Canada. GenGIS release versions, tutorials and documentation are freely available at http://kiwi.cs.dal.ca/GenGIS, and source code is available at https://github.com/beiko-lab/gengis.}, }
@article {pmid23913542, year = {2013}, author = {Inglis, DO and Sherlock, G}, title = {Ras signaling gets fine-tuned: regulation of multiple pathogenic traits of Candida albicans.}, journal = {Eukaryotic cell}, volume = {12}, number = {10}, pages = {1316-1325}, pmid = {23913542}, issn = {1535-9786}, support = {R01 DE015873/DE/NIDCR NIH HHS/United States ; }, mesh = {Biofilms ; Candida albicans/metabolism/*pathogenicity/physiology ; Fungal Proteins/genetics/*metabolism ; *Signal Transduction ; ras Proteins/genetics/*metabolism ; }, abstract = {Candida albicans is an opportunistic fungal pathogen that can cause disseminated infection in patients with indwelling catheters or other implanted medical devices. A common resident of the human microbiome, C. albicans responds to environmental signals, such as cell contact with catheter materials and exposure to serum or CO2, by triggering the expression of a variety of traits, some of which are known to contribute to its pathogenic lifestyle. Such traits include adhesion, biofilm formation, filamentation, white-to-opaque (W-O) switching, and two recently described phenotypes, finger and tentacle formation. Under distinct sets of environmental conditions and in specific cell types (mating type-like a [MTLa]/alpha cells, MTL homozygotes, or daughter cells), C. albicans utilizes (or reutilizes) a single signal transduction pathway-the Ras pathway-to affect these phenotypes. Ras1, Cyr1, Tpk2, and Pde2, the proteins of the Ras signaling pathway, are the only nontranscriptional regulatory proteins that are known to be essential for regulating all of these processes. How does C. albicans utilize this one pathway to regulate all of these phenotypes? The regulation of distinct and yet related processes by a single, evolutionarily conserved pathway is accomplished through the use of downstream transcription factors that are active under specific environmental conditions and in different cell types. In this minireview, we discuss the role of Ras signaling pathway components and Ras pathway-regulated transcription factors as well as the transcriptional regulatory networks that fine-tune gene expression in diverse biological contexts to generate specific phenotypes that impact the virulence of C. albicans.}, }
@article {pmid23906180, year = {2013}, author = {Börnigen, D and Morgan, XC and Franzosa, EA and Ren, B and Xavier, RJ and Garrett, WS and Huttenhower, C}, title = {Functional profiling of the gut microbiome in disease-associated inflammation.}, journal = {Genome medicine}, volume = {5}, number = {7}, pages = {65}, pmid = {23906180}, issn = {1756-994X}, support = {K08 AI078942/AI/NIAID NIH HHS/United States ; P30 DK043351/DK/NIDDK NIH HHS/United States ; R01 CA154426/CA/NCI NIH HHS/United States ; R01 DK092405/DK/NIDDK NIH HHS/United States ; }, abstract = {The microbial residents of the human gut are a major factor in the development and lifelong maintenance of health. The gut microbiota differs to a large degree from person to person and has an important influence on health and disease due to its interaction with the human immune system. Its overall composition and microbial ecology have been implicated in many autoimmune diseases, and it represents a particularly important area for translational research as a new target for diagnostics and therapeutics in complex inflammatory conditions. Determining the biomolecular mechanisms by which altered microbial communities contribute to human disease will be an important outcome of current functional studies of the human microbiome. In this review, we discuss functional profiling of the human microbiome using metagenomic and metatranscriptomic approaches, focusing on the implications for inflammatory conditions such as inflammatory bowel disease and rheumatoid arthritis. Common themes in gut microbial ecology have emerged among these diverse diseases, but they have not yet been linked to targetable mechanisms such as microbial gene and genome composition, pathway and transcript activity, and metabolism. Combining these microbial activities with host gene, transcript and metabolic information will be necessary to understand how and why these complex interacting systems are altered in disease-associated inflammation.}, }
@article {pmid23901633, year = {2013}, author = {Madupu, R and Szpakowski, S and Nelson, KE}, title = {Microbiome in human health and disease.}, journal = {Science progress}, volume = {96}, number = {Pt 2}, pages = {153-170}, pmid = {23901633}, issn = {0036-8504}, support = {DP3DK94343-01/DP/NCCDPHP CDC HHS/United States ; HHSN272200900007C/HH/HHS/United States ; }, mesh = {Communicable Diseases/*microbiology ; Humans ; Metagenome/*genetics ; Metagenomics/*methods ; }, abstract = {Metagenomic studies have truly revolutionised biology and medicine, and changed the way we study genomics. As genome sequencing becomes cheaper it is being applied to study complex metagenomes. 'Metagenome' is the genetic material recovered directly from an environmental sample or niche. By delivering fast, cheap, and large volumes of data Next Generation Sequencing (NGS) platforms have facilitated a deeper understanding of the fundamentals of genomes, gene functions and regulation. Metagenomics, also referred to as environmental or community genomics, has brought about radical changes in our ability to analyse complex microbial communities by direct sampling of their natural habitat paving the way for the creation of innovative new areas for biomedical research. Many metagenomic studies involving the 'human microbiome'have been undertaken to date. Samples from of a number of diverse habitats including different human body sites have been subject to metagenomic examinations. Huge national and international projects with the purpose of elucidating the biogeography of microbial communities living within and on the human body, are well underway. The analysis of human microbiome data has brought about a paradigm shift in our understanding of the role of resident microflora in human health and disease and brings non-traditional areas such as gut ecology to the forefront of personalised medicine. In this chapter we present an overview of the state-of-the-art in current literature and projects pertaining to human microbiome studies.}, }
@article {pmid23899327, year = {2013}, author = {Cui, L and Morris, A and Ghedin, E}, title = {The human mycobiome in health and disease.}, journal = {Genome medicine}, volume = {5}, number = {7}, pages = {63}, pmid = {23899327}, issn = {1756-994X}, support = {U01 HL098962/HL/NHLBI NIH HHS/United States ; }, abstract = {The mycobiome, referring primarily to the fungal biota in an environment, is an important component of the human microbiome. Despite its importance, it has remained understudied. New culture-independent approaches to determine microbial diversity, such as next-generation sequencing methods, are greatly broadening our view of fungal importance. An integrative analysis of current studies shows that different body sites harbor specific fungal populations, and that diverse mycobiome patterns are associated with various diseases. By interfacing with other biomes, as well as with the host, the mycobiome probably contributes to the progression of fungus-associated diseases and plays an important role in health and disease.}, }
@article {pmid23889754, year = {2014}, author = {Livermore, JA and Emrich, SJ and Tan, J and Jones, SE}, title = {Freshwater bacterial lifestyles inferred from comparative genomics.}, journal = {Environmental microbiology}, volume = {16}, number = {3}, pages = {746-758}, doi = {10.1111/1462-2920.12199}, pmid = {23889754}, issn = {1462-2920}, mesh = {Bacteria/classification/*genetics/*metabolism ; Carbohydrate Metabolism/genetics ; Cluster Analysis ; *Ecosystem ; Fresh Water/*microbiology ; Genetic Variation ; Genome, Bacterial/*genetics ; Genomics ; Open Reading Frames/genetics ; RNA, Ribosomal, 16S/genetics ; *Water Microbiology ; }, abstract = {While micro-organisms actively mediate and participate in freshwater ecosystem services, we know little about freshwater microbial genetic diversity. Genome sequences are available for many bacteria from the human microbiome and the ocean (over 800 and 200, respectively), but only two freshwater genomes are currently available: the streamlined genomes of Polynucleobacter necessarius ssp. asymbioticus and the Actinobacterium AcI-B1. Here, we sequenced and analysed draft genomes of eight phylogentically diverse freshwater bacteria exhibiting a range of lifestyle characteristics. Comparative genomics of these bacteria reveals putative freshwater bacterial lifestyles based on differences in predicted growth rate, capability to respond to environmental stimuli and diversity of useable carbon substrates. Our conceptual model based on these genomic characteristics provides a foundation on which further ecophysiological and genomic studies can be built. In addition, these genomes greatly expand the diversity of existing genomic context for future studies on the ecology and genetics of freshwater bacteria.}, }
@article {pmid23859205, year = {2013}, author = {Riley, MA and Robinson, SM and Roy, CM and Dorit, RL}, title = {Rethinking the composition of a rational antibiotic arsenal for the 21st century.}, journal = {Future medicinal chemistry}, volume = {5}, number = {11}, pages = {1231-1242}, doi = {10.4155/fmc.13.79}, pmid = {23859205}, issn = {1756-8927}, mesh = {Animals ; Anti-Bacterial Agents/*pharmacology/therapeutic use ; Bacterial Infections/drug therapy ; Bacteriocins/pharmacology/therapeutic use ; Bacteriophages/metabolism ; Colicins/genetics/metabolism ; Drug Resistance, Bacterial/*drug effects ; Drug Therapy, Combination ; Humans ; Imidazoles/*pharmacology/therapeutic use ; Niacin/*analogs &amp; derivatives/pharmacology/therapeutic use ; Urinary Tract Infections/drug therapy ; }, abstract = {The importance of the human microbiome in health may be the single most valuable development in our conception of the microbial world since Pasteur's germ theory of the 1860s. Its implications for our understanding of health and pathogenesis are profound. Coupled with the revolution in diagnostics that we are now witnessing - a revolution that changes medicine from a science of symptoms to a science of causes - we cannot continue to develop antibiotics as we have for the past 80 years. Instead, we need to usher in a new conception of the role of antibiotics in treatment: away from single molecules that target broad phylogenetic spectra and towards targeted molecules that cripple the pathogen while leaving the rest of the microbiome largely intact.}, }
@article {pmid23858463, year = {2013}, author = {Levy, R and Borenstein, E}, title = {Metabolic modeling of species interaction in the human microbiome elucidates community-level assembly rules.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {110}, number = {31}, pages = {12804-12809}, pmid = {23858463}, issn = {1091-6490}, support = {DP2 AT007802/AT/NCCIH NIH HHS/United States ; }, mesh = {Genome, Bacterial/*physiology ; Host-Parasite Interactions/*physiology ; Humans ; Microbiota/*physiology ; *Models, Biological ; }, abstract = {The human microbiome plays a key role in human health and is associated with numerous diseases. Metagenomic-based studies are now generating valuable information about the composition of the microbiome in health and in disease, demonstrating nonneutral assembly processes and complex co-occurrence patterns. However, the underlying ecological forces that structure the microbiome are still unclear. Specifically, compositional studies alone with no information about mechanisms of interaction, potential competition, or syntrophy, cannot clearly distinguish habitat-filtering and species assortment assembly processes. To address this challenge, we introduce a computational framework, integrating metagenomic-based compositional data with genome-scale metabolic modeling of species interaction. We use in silico metabolic network models to predict levels of competition and complementarity among 154 microbiome species and compare predicted interaction measures to species co-occurrence. Applying this approach to two large-scale datasets describing the composition of the gut microbiome, we find that species tend to co-occur across individuals more frequently with species with which they strongly compete, suggesting that microbiome assembly is dominated by habitat filtering. Moreover, species' partners and excluders exhibit distinct metabolic interaction levels. Importantly, we show that these trends cannot be explained by phylogeny alone and hold across multiple taxonomic levels. Interestingly, controlling for host health does not change the observed patterns, indicating that the axes along which species are filtered are not fully defined by macroecological host states. The approach presented here lays the foundation for a reverse-ecology framework for addressing key questions concerning the assembly of host-associated communities and for informing clinical efforts to manipulate the microbiome.}, }
@article {pmid23842540, year = {2013}, author = {Lau, S}, title = {Bacterial lysates in food allergy prevention.}, journal = {Current opinion in allergy and clinical immunology}, volume = {13}, number = {3}, pages = {293-295}, doi = {10.1097/ACI.0b013e328360ede9}, pmid = {23842540}, issn = {1473-6322}, mesh = {Allergens/immunology ; Animals ; Antigens, Bacterial/*immunology ; Bacteria/*immunology ; Cattle ; Clinical Trials as Topic ; Food Hypersensitivity/epidemiology/immunology/*prevention &amp; control ; Humans ; Incidence ; Infant ; Infant Formula ; Microbiota/immunology ; Milk/adverse effects/immunology ; Prevalence ; }, abstract = {PURPOSE OF REVIEW: In the concept of food allergy prevention, no successful strategy could be identified until now. Although interventional trials using probiotics, prebiotics, hydrolyzed formula and bacterial lysates early in infancy were found to reduce the incidence of atopic dermatitis, no effect on food sensitization and allergy could be shown.<br><br>RECENT FINDINGS: Studies in a farming environment showed that early contact to livestock, bacteria and moulds may upregulate the immune responses regulated via Toll-like receptors and thus prevent allergy. There is increasing evidence that the unbalanced composition of the human microbiome on human skin and mucosal surfaces may be a key player in the development of inflammatory diseases like allergy and asthma. However, during the last 5 years, this concept could not yet be verified in the interventional trials. There are few studies using bacterial lysates, for example, Escherichia coli plus Enterococcus faecalis in ProSymbioflor and heat-killed Bifidobacterium breve and Streptococcus thermophilus; however, food allergy prevalence could not be reduced by these interventions.<br><br>SUMMARY: During the last 5 years, new interventional trials addressed the use of bacterial lysates. There was only an effect on eczema in the ProSymbioflor trial, whereas the trial using B. breve and S. thermophilus in a cow's milk formula showed a slight reduction of food sensitization at the age of 12 months. However, these strategies need further investigation and success seems to be restricted to certain subpopulations.}, }
@article {pmid23840181, year = {2013}, author = {Riley, DR and Sieber, KB and Robinson, KM and White, JR and Ganesan, A and Nourbakhsh, S and Dunning Hotopp, JC}, title = {Bacteria-human somatic cell lateral gene transfer is enriched in cancer samples.}, journal = {PLoS computational biology}, volume = {9}, number = {6}, pages = {e1003107}, pmid = {23840181}, issn = {1553-7358}, support = {DP2 OD007372/OD/NIH HHS/United States ; 1-DP2-OD007372/OD/NIH HHS/United States ; }, mesh = {Bacteria/genetics/*isolation &amp; purification ; Base Sequence ; DNA, Bacterial/genetics ; *Gene Transfer, Horizontal ; Genes, Bacterial ; Genome, Human ; Humans ; Molecular Sequence Data ; Neoplasms/*genetics/metabolism ; Sequence Homology, Nucleic Acid ; }, abstract = {There are 10× more bacterial cells in our bodies from the microbiome than human cells. Viral DNA is known to integrate in the human genome, but the integration of bacterial DNA has not been described. Using publicly available sequence data from the human genome project, the 1000 Genomes Project, and The Cancer Genome Atlas (TCGA), we examined bacterial DNA integration into the human somatic genome. Here we present evidence that bacterial DNA integrates into the human somatic genome through an RNA intermediate, and that such integrations are detected more frequently in (a) tumors than normal samples, (b) RNA than DNA samples, and (c) the mitochondrial genome than the nuclear genome. Hundreds of thousands of paired reads support random integration of Acinetobacter-like DNA in the human mitochondrial genome in acute myeloid leukemia samples. Numerous read pairs across multiple stomach adenocarcinoma samples support specific integration of Pseudomonas-like DNA in the 5'-UTR and 3'-UTR of four proto-oncogenes that are up-regulated in their transcription, consistent with conversion to an oncogene. These data support our hypothesis that bacterial integrations occur in the human somatic genome and may play a role in carcinogenesis. We anticipate that the application of our approach to additional cancer genome projects will lead to the more frequent detection of bacterial DNA integrations in tumors that are in close proximity to the human microbiome.}, }
@article {pmid23838941, year = {2013}, author = {Quigley, EM and Monsour, HP}, title = {Targeting the microbiota in the management of gastrointestinal and liver disease.}, journal = {Revista de gastroenterologia del Peru : organo oficial de la Sociedad de Gastroenterologia del Peru}, volume = {33}, number = {2}, pages = {139-144}, pmid = {23838941}, issn = {1609-722X}, mesh = {Gastrointestinal Diseases/*microbiology/*therapy ; Humans ; Liver Diseases/*microbiology/*therapy ; *Microbiota ; }, abstract = {Thanks to rapid advances in technology the details of the human microbiome and its functions in health and disease are being progressively revealed. Though many reports have linked various disease states with an altered microbiome and while some associations between the microbiome and disease states are well established, many of these studies are largely descriptive and the changes reported in the microbiome have yet to be shown to be causative. A number of strategies are available to modify the microbiota; some such as the use of antibiotics for specific indications, are well established, others such as the use of probiotics and prebiotics in a variety of disease states are supported by more limited data. Fecal transplantation has emerged as an exciting, albeit rather drastic, intervention for intestinal and, perhaps, other disorders. Other approaches, such as the isolation, purification and formulation of small molecules with specific biological actions, derived from the microbiota look very promising.}, }
@article {pmid23837897, year = {2015}, author = {Hezel, MP and Weitzberg, E}, title = {The oral microbiome and nitric oxide homoeostasis.}, journal = {Oral diseases}, volume = {21}, number = {1}, pages = {7-16}, doi = {10.1111/odi.12157}, pmid = {23837897}, issn = {1601-0825}, mesh = {*Homeostasis/physiology ; Humans ; *Microbiota ; Mouth/metabolism/*microbiology/physiology ; Nitrates/metabolism ; Nitric Oxide/*metabolism/physiology ; Nitrites/metabolism ; Signal Transduction/physiology ; }, abstract = {The tiny radical nitric oxide (NO) participates in a vast number of physiological functions including vasodilation, nerve transmission, host defence and cellular energetics. Classically produced by a family of specific enzymes, NO synthases (NOSs), NO signals via reactions with other radicals or transition metals. An alternative pathway for the generation of NO is the nitrate-nitrite-NO pathway in which the inorganic anions nitrate (NO(3)(-)) and nitrite (NO(2)(-)) are reduced to NO and other reactive nitrogen intermediates. Nitrate and nitrite are oxidation products from NOS-dependent NO generation but also constituents in our diet, mainly in leafy green vegetables. Irrespective of origin, active uptake of circulating nitrate in the salivary glands, excretion in saliva and subsequent reduction to nitrite by oral commensal bacteria are all necessary steps for further NO generation. This central role of the oral cavity in regulating NO generation from nitrate presents a new and intriguing aspect of the human microbiome in health and disease. In this review, we present recent advances in our understanding of the nitrate-nitrite-NO pathway and specifically highlight the importance of the oral cavity as a hub for its function.}, }
@article {pmid23836415, year = {2013}, author = {Ursell, LK and Van Treuren, W and Metcalf, JL and Pirrung, M and Gewirtz, A and Knight, R}, title = {Replenishing our defensive microbes.}, journal = {BioEssays : news and reviews in molecular, cellular and developmental biology}, volume = {35}, number = {9}, pages = {810-817}, pmid = {23836415}, issn = {1521-1878}, support = {/HHMI/Howard Hughes Medical Institute/United States ; T32 GM008759/GM/NIGMS NIH HHS/United States ; T32 GM142607/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Disease ; Ecosystem ; Gastrointestinal Tract/immunology/*microbiology ; Host-Pathogen Interactions/immunology ; Humans ; *Metagenome ; *Microbiota ; Probiotics/metabolism ; }, abstract = {Large-scale characterization of the human microbiota has largely focused on Western adults, yet these populations may be uncharacteristic because of their diets and lifestyles. In particular, the rise of "Western diseases" may in part stem from reduced exposure to, or even loss of, microbes with which humans have coevolved. Here, we review beneficial microbes associated with pathogen resistance, highlighting the emerging role of complex microbial communities in protecting against disease. We discuss ways in which modern lifestyles and practices may deplete physiologically important microbiota, and explore prospects for reintroducing or encouraging the growth of beneficial microbes to promote the restoration of healthy microbial ecosystems.}, }
@article {pmid23833275, year = {2013}, author = {Evans, JM and Morris, LS and Marchesi, JR}, title = {The gut microbiome: the role of a virtual organ in the endocrinology of the host.}, journal = {The Journal of endocrinology}, volume = {218}, number = {3}, pages = {R37-47}, doi = {10.1530/JOE-13-0131}, pmid = {23833275}, issn = {1479-6805}, mesh = {Bacteria/isolation &amp; purification ; Bacterial Physiological Phenomena ; Endocrine System/*metabolism ; Gastrointestinal Tract/metabolism/*microbiology ; Humans ; *Metagenome ; }, abstract = {The human microbiome contains a vast array of microbes and genes that show greater complexity than the host's own karyome; the functions of many of these microbes are beneficial and show co-evolution with the host, while others are detrimental. The microbiota that colonises the gut is now being considered as a virtual organ or emergent system, with properties that need to be integrated into host biology and physiology. Unlike other organs, the functions that the gut microbiota plays in the host are as yet not fully understood and can be quite easily disrupted by antibiotics, diet or surgery. In this review, we look at some of the best-characterised functions that only the gut microbiota plays and how it interacts with the host's endocrine system and we try to make it clear that the 21st-century biology cannot afford to ignore this facet of biology, if it wants to fully understand what makes us human.}, }
@article {pmid23828150, year = {2013}, author = {Marcinkiewicz, J and Strus, M and Pasich, E}, title = {Antibiotic resistance: a "dark side" of biofilm‑associated chronic infections.}, journal = {Polskie Archiwum Medycyny Wewnetrznej}, volume = {123}, number = {6}, pages = {309-313}, pmid = {23828150}, mesh = {Antibiotic Prophylaxis ; Bacteria/*metabolism ; Bacterial Infections/*drug therapy ; Biofilms/*drug effects ; Chronic Disease ; *Drug Resistance, Microbial ; Humans ; Inflammation/microbiology/prevention &amp; control ; Periodontitis/drug therapy/microbiology ; }, abstract = {Bacteria may exist in nature in a planktonic form or in biofilms that allow bacteria to survive in an unfriendly microenvironment. Biofilm is a structured community of bacteria hidden in a self-produced polymeric matrix of polysaccharides, proteins, and extracellular DNA. Biofilm-growing bacteria cause chronic infections, which are characterized by persisting inflammation and tissue damage (chronic rhinosinusitis, chronic wounds, periodontal diseases). Importantly, some bacteria of human microbiome, when growing in a biofilm (e.g., Porphyromonas gingivalis in dental plaque), can become destructive and can contribute to an association between local infections (periodontitis) and systemic diseases such as atherosclerosis or rheumatoid arthritis. The biggest clinical challenge with biofilm-associated infections is their high resistance to antibiotic therapy. Therefore, biofilm formation should be prevented either by antibiotic prophylaxis or early aggressive pharmacological therapy. In this review, we also discuss novel antibiofilm therapeutic strategies based on compounds that can destroy the biofilm matrix and increase susceptibility of biofilm-forming bacteria to antibiotics and host defense system.}, }
@article {pmid23822674, year = {2013}, author = {Gil, A}, title = {Third Jesús Culebras Lecture - Molecular biology and clinical nutrition; where do we stand and where do we go?.}, journal = {Nutricion hospitalaria}, volume = {28}, number = {2}, pages = {241-249}, doi = {10.3305/nh.2013.28.2.6424}, pmid = {23822674}, issn = {1699-5198}, mesh = {Animals ; Biomarkers ; Humans ; Metabolomics ; Microbiota ; Molecular Biology/*trends ; Nutrigenomics ; Nutritional Sciences/*trends ; Precision Medicine ; Probiotics ; }, abstract = {Nutrition plays a fundamental role in the maintenance of health and the treatment of disease, and serves as the crossroads for many disciplines. Biochemistry and Molecular Biology represents a key brand of science to ascertain the mechanism of action of nutrients and other food bioactive compounds in health and disease. The aim of the present Jesús M. Culebras lecture is to consider the future of the relationships between Molecular Biology and Clinical Nutrition and to discuss the use of molecular and genetic tools to study molecular responses to dietary factors and the metabolic consequences of food and to consider major challenges on human nutrition sciences in the 21(st) century. Particular emphasis is given to the identification and use of novel biomarkers in inflammatory diseases. Likewise, the importance of the human microbiome and how microorganisms can be safely utilized in the prevention and management of infectious and chronic diseases are discussed. Moreover, the key role of nutrigenetics, nutrigenomics and epigenetics in the new era of nutrition is considered. Nutrigenetics refers to the role of DNA sequence variation in the responses to nutrients, whereas nutrigenomics is the study of the role of nutrients in gene expression. Epigenetics is the study of mitotically heritable alterations in gene expression potential that are not caused by DNA sequence alterations. In the past decade, it has increasingly been recognized that dysregulation of epigenetic mechanisms may play an important role in human disease. Indeed, there is increasing interest in epigenetic mechanisms underlying phenotype modification modulated by nutrients. Further research in those areas should contribute to evaluate functionality of specific nutrients and bioactive compounds in Clinical Nutrition and allow personalized nutritional advice.}, }
@article {pmid23802897, year = {2013}, author = {Hoffmann, DE and Fortenberry, JD and Ravel, J}, title = {Are changes to the common rule necessary to address evolving areas of research? A case study focusing on the human microbiome project.}, journal = {The Journal of law, medicine &amp; ethics : a journal of the American Society of Law, Medicine &amp; Ethics}, volume = {41}, number = {2}, pages = {454-469}, pmid = {23802897}, issn = {1748-720X}, support = {R01 HG005171/HG/NHGRI NIH HHS/United States ; }, mesh = {Human Experimentation/*legislation &amp; jurisprudence ; Humans ; *Metagenome ; National Institutes of Health (U.S.) ; Patient Selection ; Research Subjects/*legislation &amp; jurisprudence ; Social Stigma ; United States ; }, abstract = {This article examines ways in which research conducted under the Human Microbiome Project, an effort to establish a "reference catalogue" of the micro-organisms present in the human body and determine how changes in those micro-organisms affect health and disease, raise challenging issues for regulation of human subject research. The article focuses on issues related to subject selection and recruitment, group stigma, and informational risks, and explores whether: (1) the Common Rule or proposed changes to the Rule adequately address these issues and (2) the Common Rule is the most appropriate vehicle to provide regulatory oversight and guidance on these topics.}, }
@article {pmid23776475, year = {2013}, author = {Probst, AJ and Auerbach, AK and Moissl-Eichinger, C}, title = {Archaea on human skin.}, journal = {PloS one}, volume = {8}, number = {6}, pages = {e65388}, pmid = {23776475}, issn = {1932-6203}, mesh = {Ammonia/metabolism ; Archaea/*genetics/metabolism ; Azides ; Base Sequence ; Bayes Theorem ; Cloning, Molecular ; DNA Primers/genetics ; Germany ; Humans ; In Situ Hybridization, Fluorescence ; Microbiota/*genetics ; Models, Genetic ; Molecular Sequence Data ; Oxidation-Reduction ; *Phylogeny ; Propidium/analogs &amp; derivatives ; RNA, Ribosomal, 16S/genetics ; Real-Time Polymerase Chain Reaction ; Sequence Analysis, DNA ; Skin/*microbiology ; }, abstract = {The recent era of exploring the human microbiome has provided valuable information on microbial inhabitants, beneficials and pathogens. Screening efforts based on DNA sequencing identified thousands of bacterial lineages associated with human skin but provided only incomplete and crude information on Archaea. Here, we report for the first time the quantification and visualization of Archaea from human skin. Based on 16 S rRNA gene copies Archaea comprised up to 4.2% of the prokaryotic skin microbiome. Most of the gene signatures analyzed belonged to the Thaumarchaeota, a group of Archaea we also found in hospitals and clean room facilities. The metabolic potential for ammonia oxidation of the skin-associated Archaea was supported by the successful detection of thaumarchaeal amoA genes in human skin samples. However, the activity and possible interaction with human epithelial cells of these associated Archaea remains an open question. Nevertheless, in this study we provide evidence that Archaea are part of the human skin microbiome and discuss their potential for ammonia turnover on human skin.}, }
@article {pmid23734710, year = {2013}, author = {Ander, C and Schulz-Trieglaff, OB and Stoye, J and Cox, AJ}, title = {metaBEETL: high-throughput analysis of heterogeneous microbial populations from shotgun DNA sequences.}, journal = {BMC bioinformatics}, volume = {14 Suppl 5}, number = {Suppl 5}, pages = {S2}, pmid = {23734710}, issn = {1471-2105}, mesh = {Algorithms ; Environmental Microbiology ; High-Throughput Nucleotide Sequencing/*methods ; Humans ; Metagenomics/*methods ; *Microbiota ; Phylogeny ; Sequence Analysis, DNA/*methods ; }, abstract = {Environmental shotgun sequencing (ESS) has potential to give greater insight into microbial communities than targeted sequencing of 16S regions, but requires much higher sequence coverage. The advent of next-generation sequencing has made it feasible for the Human Microbiome Project and other initiatives to generate ESS data on a large scale, but computationally efficient methods for analysing such data sets are needed.Here we present metaBEETL, a fast taxonomic classifier for environmental shotgun sequences. It uses a Burrows-Wheeler Transform (BWT) index of the sequencing reads and an indexed database of microbial reference sequences. Unlike other BWT-based tools, our method has no upper limit on the number or the total size of the reference sequences in its database. By capturing sequence relationships between strains, our reference index also allows us to classify reads which are not unique to an individual strain but are nevertheless specific to some higher phylogenetic order.Tested on datasets with known taxonomic composition, metaBEETL gave results that are competitive with existing similarity-based tools: due to normalization steps which other classifiers lack, the taxonomic profile computed by metaBEETL closely matched the true environmental profile. At the same time, its moderate running time and low memory footprint allow metaBEETL to scale well to large data sets.Code to construct the BWT indexed database and for the taxonomic classification is part of the BEETL library, available as a github repository at git@github.com:BEETL/BEETL.git.}, }
@article {pmid23747703, year = {2013}, author = {Tu, Q and He, Z and Deng, Y and Zhou, J}, title = {Strain/species-specific probe design for microbial identification microarrays.}, journal = {Applied and environmental microbiology}, volume = {79}, number = {16}, pages = {5085-5088}, pmid = {23747703}, issn = {1098-5336}, mesh = {Bacteria/*classification/*genetics ; *Genes, Bacterial ; Humans ; *Metagenome ; Oligonucleotide Array Sequence Analysis/*methods ; Oligonucleotide Probes/*genetics ; Species Specificity ; }, abstract = {Specific identification of microorganisms in the environment is important but challenging, especially at the species/strain level. Here, we have developed a novel k-mer-based approach to select strain/species-specific probes for microbial identification with diagnostic microarrays. Application of this approach to human microbiome genomes showed that multiple (≥10 probes per strain) strain-specific 50-mer oligonucleotide probes could be designed for 2,012 of 3,421 bacterial strains of the human microbiome, and species-specific probes could be designed for most of the other strains. The method can also be used to select strain/species-specific probes for sequenced genomes in any environments, such as soil and water.}, }
@article {pmid23743600, year = {2013}, author = {Jeon, YS and Chun, J and Kim, BS}, title = {Identification of household bacterial community and analysis of species shared with human microbiome.}, journal = {Current microbiology}, volume = {67}, number = {5}, pages = {557-563}, pmid = {23743600}, issn = {1432-0991}, mesh = {Bacteria/*classification/*genetics ; Computational Biology/methods ; Environmental Microbiology ; *Family Characteristics ; Humans ; *Metagenome ; *Microbiota ; RNA, Ribosomal, 16S ; Sequence Analysis, DNA ; }, abstract = {Microbial populations in indoor environments, where we live and eat, are important for public health. Various bacterial species reside in the kitchen, and refrigerators, the major means of food storage within kitchens, can be a direct source of food borne illness. Therefore, the monitoring of microbiota in the refrigerator is important for food safety. We investigated and compared bacterial communities that reside in the vegetable compartment of the refrigerator and on the seat of the toilet, which is recognized as highly colonized by microorganisms, in ten houses using high-throughput sequencing. Proteobacteria, Firmicutes, Actinobacteria, and Bacteroidetes were predominant in refrigerator and toilet samples. However, Proteobacteria was more abundant in the refrigerator, and Firmicutes was more abundant in the toilet. These household bacterial communities were compared with those of human skin and gut to identify potential sources of household bacteria. Bacterial communities from refrigerators and toilets shared more species in common with human skin than gut. Opportunistic pathogens, including Propionibacterium acnes, Bacteroides vulgatus, and Staphylococcus epidermidis, were identified as species shared with human skin and gut microbiota. This approach can provide a general background of the household microbiota and a potential method of source-tracking for public health purposes.}, }
@article {pmid23732897, year = {2013}, author = {Spero, D and Levitz, L and De Groot, AS}, title = {Report from the field: Overview of the Sixth Annual Vaccine Renaissance Conference.}, journal = {Human vaccines &amp; immunotherapeutics}, volume = {9}, number = {7}, pages = {1555-1557}, pmid = {23732897}, issn = {2164-554X}, support = {R13 AI094946/AI/NIAID NIH HHS/United States ; U19 AI082642/AI/NIAID NIH HHS/United States ; U19AI082642-01/AI/NIAID NIH HHS/United States ; R13AI094946-01/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; *Biological Warfare ; *Biological Warfare Agents ; Cattle ; Clostridioides difficile/immunology ; Enterocolitis, Pseudomembranous/immunology/prevention &amp; control ; Enterotoxins/immunology ; Hepatitis C/immunology/prevention &amp; control ; Humans ; Malaria/immunology/prevention &amp; control ; Malaria Vaccines/immunology ; Mice ; Pandemics/*prevention &amp; control ; Plasmodium berghei/immunology ; Tropical Climate ; Tularemia/immunology/prevention &amp; control ; Vaccines/*immunology ; Viral Hepatitis Vaccines/immunology ; }, abstract = {The Sixth Annual Vaccine Renaissance Conference, hosted by the Institute for Immunology and Informatics (iCubed) at the University of Rhode Island (URI), took place on October 15-17, 2012. This conference provides a forum for the review of current progress in the discovery and development of vaccines, and creates an environment for the exchange of ideas. Dr. Joel McCleary opened the conference with a warning about the importance of preparing for well-defined biowarfare threats, including tularemia and Staphylococcal enterotoxin B. Following the keynote address, sessions explored biodefense and preparation for pandemic and biowarfare threats; vaccines for emerging and re-emerging neglected tropical diseases; animal vaccines and human health; and vaccine vectors and the human microbiome. In this issue of Human Vaccines and Immunotherapeutics, seven Vaccine Renaissance Conference speakers will showcase their work; here, we describe a few of the conference highlights.}, }
@article {pmid23707554, year = {2013}, author = {Nagalingam, NA and Cope, EK and Lynch, SV}, title = {Probiotic strategies for treatment of respiratory diseases.}, journal = {Trends in microbiology}, volume = {21}, number = {9}, pages = {485-492}, doi = {10.1016/j.tim.2013.04.008}, pmid = {23707554}, issn = {1878-4380}, mesh = {Animals ; Gastrointestinal Tract/microbiology ; Humans ; Microbiota ; Probiotics/*therapeutic use ; Respiratory Tract Diseases/*drug therapy ; }, abstract = {Recent advances in next-generation sequencing and phylogenetic microarray technologies have identified diverse, niche-specific microbial communities that comprise the human superorganism. Mucosal microbiome perturbation is a prominent feature of an increasing number of chronic inflammatory disorders, including respiratory diseases, and efforts are now focused on identifying novel microbe-based strategies to treat or manage these conditions. Considering the evidence for niche-specificity and the diversity of function that human microbial communities afford, the range of therapeutic species used to date in probiotic supplements is strikingly narrow and is limited to species typically of gastrointestinal origin. Although the field is still relatively nascent, the potential for identifying novel microbe-based therapeutics in the human microbiome is great. This article focuses primarily on the respiratory tract, its associated microbiome, potential interactions with the gastrointestinal microbiota, and the possibilities for microbiome-manipulation strategies in the treatment and prevention of respiratory disease.}, }
@article {pmid23707234, year = {2014}, author = {Kolmeder, CA and de Vos, WM}, title = {Metaproteomics of our microbiome - developing insight in function and activity in man and model systems.}, journal = {Journal of proteomics}, volume = {97}, number = {}, pages = {3-16}, doi = {10.1016/j.jprot.2013.05.018}, pmid = {23707234}, issn = {1876-7737}, support = {250172/ERC_/European Research Council/International ; }, mesh = {Animals ; Bacteria/genetics/*metabolism ; Bacterial Proteins/genetics/*metabolism ; Humans ; Metagenome/physiology ; Mice ; Microbiota/*physiology ; Proteomics/*methods/trends ; }, abstract = {We are all colonized by a large microbiome, a complex set of microbes that have intimate associations with us. Culture-based approaches have provided insights in the complexity of the microbial communities living on surfaces inside and outside the body. However, the application of high-throughput sequencing technologies has identified large numbers of community members at both the phylogenetic and the (meta-)genome level. The latter allowed defining a reference set of several millions of mainly bacterial genes and provided the basis for developing approaches to target the activity and function of the human microbiome with proteomic techniques. Moreover, recent improvements in protein and peptide separation efficiencies and highly accurate mass spectrometers have promoted the field of metaproteomics, the study of the collective proteome of microbial communities. We here review the approaches that have been developed to study the human metaproteomes, focusing on intestinal tract and body fluids. Moreover, we complement these by considering metaproteomic studies in mouse and other model systems offering the option to study single species or simple consortia. Finally, we discuss present and future avenues that may be used to advance the application of metaproteomic approaches to further improve our understanding of the microbes inside and around our body. This article is part of a Special Issue entitled: Trends in Microbial Proteomics.}, }
@article {pmid23704890, year = {2013}, author = {Boyd, PW and Rynearson, TA and Armstrong, EA and Fu, F and Hayashi, K and Hu, Z and Hutchins, DA and Kudela, RM and Litchman, E and Mulholland, MR and Passow, U and Strzepek, RF and Whittaker, KA and Yu, E and Thomas, MK}, title = {Marine phytoplankton temperature versus growth responses from polar to tropical waters--outcome of a scientific community-wide study.}, journal = {PloS one}, volume = {8}, number = {5}, pages = {e63091}, pmid = {23704890}, issn = {1932-6203}, mesh = {Aquatic Organisms/*growth &amp; development/isolation &amp; purification ; *Ecosystem ; Humans ; Oceans and Seas ; Phytoplankton/*growth &amp; development/isolation &amp; purification ; Species Specificity ; *Temperature ; *Tropical Climate ; Water ; }, abstract = {"It takes a village to finish (marine) science these days" Paraphrased from Curtis Huttenhower (the Human Microbiome project) The rapidity and complexity of climate change and its potential effects on ocean biota are challenging how ocean scientists conduct research. One way in which we can begin to better tackle these challenges is to conduct community-wide scientific studies. This study provides physiological datasets fundamental to understanding functional responses of phytoplankton growth rates to temperature. While physiological experiments are not new, our experiments were conducted in many laboratories using agreed upon protocols and 25 strains of eukaryotic and prokaryotic phytoplankton isolated across a wide range of marine environments from polar to tropical, and from nearshore waters to the open ocean. This community-wide approach provides both comprehensive and internally consistent datasets produced over considerably shorter time scales than conventional individual and often uncoordinated lab efforts. Such datasets can be used to parameterise global ocean model projections of environmental change and to provide initial insights into the magnitude of regional biogeographic change in ocean biota in the coming decades. Here, we compare our datasets with a compilation of literature data on phytoplankton growth responses to temperature. A comparison with prior published data suggests that the optimal temperatures of individual species and, to a lesser degree, thermal niches were similar across studies. However, a comparison of the maximum growth rate across studies revealed significant departures between this and previously collected datasets, which may be due to differences in the cultured isolates, temporal changes in the clonal isolates in cultures, and/or differences in culture conditions. Such methodological differences mean that using particular trait measurements from the prior literature might introduce unknown errors and bias into modelling projections. Using our community-wide approach we can reduce such protocol-driven variability in culture studies, and can begin to address more complex issues such as the effect of multiple environmental drivers on ocean biota.}, }
@article {pmid23680493, year = {2013}, author = {Wallace, BD and Redinbo, MR}, title = {The human microbiome is a source of therapeutic drug targets.}, journal = {Current opinion in chemical biology}, volume = {17}, number = {3}, pages = {379-384}, pmid = {23680493}, issn = {1879-0402}, support = {R01 CA098468/CA/NCI NIH HHS/United States ; CA78924/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Drug Discovery ; Drug-Related Side Effects and Adverse Reactions/microbiology ; Health ; Humans ; Microbiota/*drug effects ; Molecular Targeted Therapy/*methods ; Pharmaceutical Preparations/metabolism ; }, abstract = {It was appreciated early in drug discovery that the microbiota play an important role in the efficacy of therapeutic compounds. Indeed, the first antibiotic sulfa drugs were shown in the 1940s to be transformed by the bacteria that encode what we now call the intestinal microbiome. Here we briefly review the roles symbiotic bacteria play in the chemistry of human health, and we focus on the emerging appreciation that specific enzyme targets expressed by microbial symbiotes can be selectively disrupted to achieve clinical outcomes. We conclude that components of the microbiome should be considered 'druggable targets,' and we suggest that our rapidly evolving understanding of the chemical biology of mammalian-microbial symbiosis will translate into improved human health.}, }
@article {pmid23674263, year = {2013}, author = {Simón-Soro, A and Tomás, I and Cabrera-Rubio, R and Catalan, MD and Nyvad, B and Mira, A}, title = {Microbial geography of the oral cavity.}, journal = {Journal of dental research}, volume = {92}, number = {7}, pages = {616-621}, doi = {10.1177/0022034513488119}, pmid = {23674263}, issn = {1544-0591}, mesh = {Actinobacillus/classification ; Actinomycetaceae/classification ; Adult ; Bacteria/*classification ; Bicuspid/microbiology ; Capnocytophaga/classification ; Cuspid/microbiology ; DNA, Bacterial/analysis ; Dental Plaque/microbiology ; Fusobacterium/classification ; Gingiva/microbiology ; Haemophilus/classification ; Humans ; Incisor/microbiology ; Male ; Molar/microbiology ; Mouth/*microbiology ; Mouth Mucosa/microbiology ; Palate/microbiology ; Polymerase Chain Reaction ; Prevotella/classification ; RNA, Bacterial/analysis ; RNA, Ribosomal, 16S/analysis ; Saliva/microbiology ; Streptococcus/classification ; Tongue/microbiology ; Veillonella/classification ; Young Adult ; }, abstract = {We aimed to determine the bacterial diversity of different oral micro-niches and to assess whether saliva and plaque samples are representative of oral microbial composition. We took minute samples from each surface of the individual teeth and gingival crevices of two healthy volunteers (112 samples per donor), as well as samples from the tongue dorsum and non-stimulated and stimulated saliva. DNA was extracted from 67 selected samples of each donor, and the 16S rRNA gene was amplified by PCR and pyrosequenced to obtain, on average, over 2,700 reads per sample, which were taxonomically assigned to obtain a geographic map of bacterial diversity at each tooth and sulcus location. Analysis of the data shows considerable differences in bacterial composition between teeth at different intra-oral locations and between surfaces of the same tooth. The most pronounced differences were observed in incisors and canines, where genera like Streptococcus were found at 40% to 70% on the vestibular surfaces but were almost absent on the lingual sides. Saliva samples, especially non-stimulated saliva, were not representative of supra-and subgingival plaque in the two individuals tested. We suggest that more precise sampling is required for the proper determination of oral microbial composition and to relate that diversity to epidemiological, clinical, and etiological parameters.}, }
@article {pmid23671663, year = {2013}, author = {Li, K and Bihan, M and Methé, BA}, title = {Analyses of the stability and core taxonomic memberships of the human microbiome.}, journal = {PloS one}, volume = {8}, number = {5}, pages = {e63139}, pmid = {23671663}, issn = {1932-6203}, support = {U54 AI084844/AI/NIAID NIH HHS/United States ; AI084844/AI/NIAID NIH HHS/United States ; }, mesh = {Bacteria/classification/*genetics ; Feces/microbiology ; Female ; Humans ; *Microbiota ; Molecular Typing ; Mouth/microbiology ; Phylogeny ; RNA, Bacterial/genetics ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; Skin/microbiology ; Vagina/microbiology ; }, abstract = {Analyses of the taxonomic diversity associated with the human microbiome continue to be an area of great importance. The study of the nature and extent of the commonly shared taxa ("core"), versus those less prevalent, establishes a baseline for comparing healthy and diseased groups by quantifying the variation among people, across body habitats and over time. The National Institutes of Health (NIH) sponsored Human Microbiome Project (HMP) has provided an unprecedented opportunity to examine and better define what constitutes the taxonomic core within and across body habitats and individuals through pyrosequencing-based profiling of 16S rRNA gene sequences from oral, skin, distal gut (stool), and vaginal body habitats from over 200 healthy individuals. A two-parameter model is introduced to quantitatively identify the core taxonomic members of each body habitat's microbiota across the healthy cohort. Using only cutoffs for taxonomic ubiquity and abundance, core taxonomic members were identified for each of the 18 body habitats and also for the 4 higher-level body regions. Although many microbes were shared at low abundance, they exhibited a relatively continuous spread in both their abundance and ubiquity, as opposed to a more discretized separation. The numbers of core taxa members in the body regions are comparatively small and stable, reflecting the relatively high, but conserved, interpersonal variability within the cohort. Core sizes increased across the body regions in the order of: vagina, skin, stool, and oral cavity. A number of "minor" oral taxonomic core were also identified by their majority presence across the cohort, but with relatively low and stable abundances. A method for quantifying the difference between two cohorts was introduced and applied to samples collected on a second visit, revealing that over time, the oral, skin, and stool body regions tended to be more transient in their taxonomic structure than the vaginal body region.}, }
@article {pmid23638391, year = {2013}, author = {Meadow, JF and Bateman, AC and Herkert, KM and O'Connor, TK and Green, JL}, title = {Significant changes in the skin microbiome mediated by the sport of roller derby.}, journal = {PeerJ}, volume = {1}, number = {}, pages = {e53}, pmid = {23638391}, issn = {2167-8359}, abstract = {Diverse bacterial communities live on and in human skin. These complex communities vary by skin location on the body, over time, between individuals, and between geographic regions. Culture-based studies have shown that human to human and human to surface contact mediates the dispersal of pathogens, yet little is currently known about the drivers of bacterial community assembly patterns on human skin. We hypothesized that participation in a sport involving skin to skin contact would result in detectable shifts in skin bacterial community composition. We conducted a study during a flat track roller derby tournament, and found that teammates shared distinct skin microbial communities before and after playing against another team, but that opposing teams' bacterial communities converged during the course of a roller derby bout. Our results are consistent with the hypothesis that the human skin microbiome shifts in composition during activities involving human to human contact, and that contact sports provide an ideal setting in which to evaluate dispersal of microorganisms between people.}, }
@article {pmid23631911, year = {2013}, author = {Tomida, S and Nguyen, L and Chiu, BH and Liu, J and Sodergren, E and Weinstock, GM and Li, H}, title = {Pan-genome and comparative genome analyses of propionibacterium acnes reveal its genomic diversity in the healthy and diseased human skin microbiome.}, journal = {mBio}, volume = {4}, number = {3}, pages = {e00003-13}, pmid = {23631911}, issn = {2150-7511}, support = {UH2AR057503/AR/NIAMS NIH HHS/United States ; R01GM099530/GM/NIGMS NIH HHS/United States ; U54 HG004968/HG/NHGRI NIH HHS/United States ; UH2 AR057503/AR/NIAMS NIH HHS/United States ; U54HG004968/HG/NHGRI NIH HHS/United States ; R01 GM099530/GM/NIGMS NIH HHS/United States ; }, mesh = {Acne Vulgaris/*microbiology ; Cluster Analysis ; Genes, Bacterial ; *Genetic Variation ; *Genome, Bacterial ; Gram-Positive Bacterial Infections/*microbiology ; Humans ; Molecular Sequence Data ; Phylogeny ; Propionibacterium acnes/*classification/*genetics/isolation &amp; purification ; Sequence Analysis, DNA ; Skin/*microbiology ; Synteny ; }, abstract = {UNLABELLED: Propionibacterium acnes constitutes a major part of the skin microbiome and contributes to human health. However, it has also been implicated as a pathogenic factor in several diseases, including acne, one of the most common skin diseases. Its pathogenic role, however, remains elusive. To better understand the genetic landscape and diversity of the organism and its role in human health and disease, we performed a comparative genome analysis of 82 P. acnes strains, 69 of which were sequenced by our group. This collection covers all known P. acnes lineages, including types IA, IB, II, and III. Our analysis demonstrated that although the P. acnes pan-genome is open, it is relatively small and expands slowly. The core regions, shared by all the sequenced genomes, accounted for 88% of the average genome. Comparative genome analysis showed that within each lineage, the strains isolated from the same individuals were more closely related than the ones isolated from different individuals, suggesting that clonal expansions occurred within each individual microbiome. We also identified the genetic elements specific to each lineage. Differences in harboring these elements may explain the phenotypic and functional differences of P. acnes in functioning as a commensal in healthy skin and as a pathogen in diseases. Our findings of the differences among P. acnes strains at the genome level underscore the importance of identifying the human microbiome variations at the strain level in understanding its association with diseases and provide insight into novel and personalized therapeutic approaches for P. acnes-related diseases.<br><br>IMPORTANCE: Propionibacterium acnes is a major human skin bacterium. It plays an important role in maintaining skin health. However, it has also been hypothesized to be a pathogenic factor in several diseases, including acne, a common skin disease affecting 85% of teenagers. To understand whether different strains have different virulent properties and thus play different roles in health and diseases, we compared the genomes of 82 P. acnes strains, most of which were isolated from acne or healthy skin. We identified lineage-specific genetic elements that may explain the phenotypic and functional differences of P. acnes as a commensal in health and as a pathogen in diseases. By analyzing a large number of sequenced strains, we provided an improved understanding of the genetic landscape and diversity of the organism at the strain level and at the molecular level that can be further applied in the development of new and personalized therapies.}, }
@article {pmid23623295, year = {2013}, author = {Greenblum, S and Chiu, HC and Levy, R and Carr, R and Borenstein, E}, title = {Towards a predictive systems-level model of the human microbiome: progress, challenges, and opportunities.}, journal = {Current opinion in biotechnology}, volume = {24}, number = {4}, pages = {810-820}, pmid = {23623295}, issn = {1879-0429}, support = {DP2 AT007802/AT/NCCIH NIH HHS/United States ; }, mesh = {Bacteria/metabolism ; Ecosystem ; Gastrointestinal Tract/microbiology ; Humans ; *Microbiota ; *Models, Biological ; }, abstract = {The human microbiome represents a vastly complex ecosystem that is tightly linked to our development, physiology, and health. Our increased capacity to generate multiple channels of omic data from this system, brought about by recent advances in high throughput molecular technologies, calls for the development of systems-level methods and models that take into account not only the composition of genes and species in a microbiome but also the interactions between these components. Such models should aim to study the microbiome as a community of species whose metabolisms are tightly intertwined with each other and with that of the host, and should be developed with a view towards an integrated, comprehensive, and predictive modeling framework. Here, we review recent work specifically in metabolic modeling of the human microbiome, highlighting both novel methodologies and pressing challenges. We discuss various modeling approaches that lay the foundation for a full-scale predictive model, focusing on models of interactions between microbial species, metagenome-scale models of community-level metabolism, and models of the interaction between the microbiome and the host. Continued development of such models and of their integration into a multi-scale model of the microbiome will lead to a deeper mechanistic understanding of how variation in the microbiome impacts the host, and will promote the discovery of clinically relevant and ecologically relevant insights from the rich trove of data now available.}, }
@article {pmid23616784, year = {2013}, author = {Penders, J and Stobberingh, EE and Savelkoul, PH and Wolffs, PF}, title = {The human microbiome as a reservoir of antimicrobial resistance.}, journal = {Frontiers in microbiology}, volume = {4}, number = {}, pages = {87}, pmid = {23616784}, issn = {1664-302X}, abstract = {The gut microbiota is amongst the most densely populated microbial ecosystem on earth. While the microbiome exerts numerous health beneficial functions, the high density of micro-organisms within this ecosystem also facilitates horizontal transfer of antimicrobial resistance (AMR) genes to potential pathogenic bacteria. Over the past decades antibiotic susceptibility testing of specific indicator bacteria from the microbiome, such as Escherichia coli, has been the method of choice in most studies. These studies have greatly enlarged our understanding on the prevalence and distribution of AMR and associated risk factors. Recent studies using (functional) metagenomics, however, highlighted the unappreciated diversity of AMR genes in the human microbiome and identified genes that had not been described previously. Next to metagenomics, more targeted approaches such as polymerase chain reaction for detection and quantification of AMR genes within a population are promising, in particular for large-scale epidemiological screening. Here we present an overview of the indigenous microbiota as a reservoir of AMR genes, the current knowledge on this "resistome" and the recent and upcoming advances in the molecular diagnostic approaches to unravel this reservoir.}, }
@article {pmid23615375, year = {2013}, author = {Slashinski, MJ and Whitney, SN and Achenbaum, LS and Keitel, WA and McCurdy, SA and McGuire, AL}, title = {Investigators' perspectives on translating human microbiome research into clinical practice.}, journal = {Public health genomics}, volume = {16}, number = {3}, pages = {127-133}, pmid = {23615375}, issn = {1662-8063}, support = {R01 HG004853/HG/NHGRI NIH HHS/United States ; R01HG004853/HG/NHGRI NIH HHS/United States ; }, mesh = {Anti-Bacterial Agents/administration &amp; dosage ; *Biomedical Research ; Humans ; *Microbiota ; *Research Personnel ; }, abstract = {BACKGROUND: Human microbiome research has the potential to transform the practice of medicine, fundamentally shifting the ways in which we think not only about human health, illness and disease, but also about clinical practice and public health interventions. Drawing from a larger qualitative study on ethical, legal and social dimensions of human microbiome research, in this article, we document perspectives related to the translation of human microbiome research into clinical practice, focusing particularly on implications for health, illness and disease.<br><br>METHODS: We conducted 60 in-depth, semi-structured interviews (2009-2010) with 63 researchers and National Institutes of Health project leaders ('investigators') involved with human microbiome research. The interviews explored a range of ethical, legal and social implications of human microbiome research, including investigators' perspectives on potential strategies for translating findings to clinical practice. Using thematic content analysis, we identified and analyzed emergent themes and patterns.<br><br>RESULTS: We identified 3 themes: (1) investigators' general perspectives on the clinical utility of human microbiome research, (2) investigators' perspectives on antibiotic use, overuse and misuse, and (3) investigators' perspectives concerning future challenges of translating data to clinical practice.<br><br>CONCLUSION: The issues discussed by investigators concerning the clinical significance of human microbiome research, including embracing a new paradigm of health and disease, the importance of microbial communities, and clinical utility, will be of critical importance as this research moves forward.}, }
@article {pmid23614695, year = {2013}, author = {Huang, YJ and Charlson, ES and Collman, RG and Colombini-Hatch, S and Martinez, FD and Senior, RM}, title = {The role of the lung microbiome in health and disease. A National Heart, Lung, and Blood Institute workshop report.}, journal = {American journal of respiratory and critical care medicine}, volume = {187}, number = {12}, pages = {1382-1387}, pmid = {23614695}, issn = {1535-4970}, support = {K23 HL105572/HL/NHLBI NIH HHS/United States ; }, mesh = {Biomedical Research ; Education ; Humans ; Intestines/microbiology ; Lung/*microbiology ; Lung Diseases/*microbiology ; *Metagenome ; Practice Guidelines as Topic ; }, abstract = {Study of the human lung microbiome in the context of pulmonary health and disease is an area of emerging research interest that is being driven by several contributing factors. These factors include increased recognition of the diversity of human-associated microbiota, their roles in health and in diseases associated with chronic inflammation, and advancements in technologies and tools that have facilitated such discoveries about the microbiota in organ systems outside of the lung. Therefore, the overarching goals of lung microbiome research are: to identify and characterize microbial populations associated with the respiratory tract and lungs; to understand their roles in lung health and disease; and, we hope, to allow the development of improved approaches for diagnosing and treating chronic respiratory diseases in which the microbiome has a role. Recent studies of the lung microbiome have yielded a number of interesting findings but also highlighted questions and challenges for researchers and clinicians. In December 2011, the National Heart, Lung, and Blood Institute convened a workshop to identify key issues and areas for further attention or development to advance research on the lung microbiome. Current knowledge and the state of research on the lung and related areas of human microbiome investigation were reviewed and discussed.}, }
@article {pmid23611298, year = {2013}, author = {Dreyfus, DH}, title = {Herpesviruses and the microbiome.}, journal = {The Journal of allergy and clinical immunology}, volume = {132}, number = {6}, pages = {1278-1286}, doi = {10.1016/j.jaci.2013.02.039}, pmid = {23611298}, issn = {1097-6825}, mesh = {Animals ; Child ; Gene-Environment Interaction ; Herpesviridae/*immunology ; Herpesviridae Infections/complications/*immunology ; Humans ; Hypersensitivity/complications/*immunology ; Immunomodulation ; Microbiota/*immunology ; Skin/*immunology/pathology/virology ; }, abstract = {The focus of this article will be to examine the role of common herpesviruses as a component of the microbiome of atopic patients and to review clinical observations suggesting that atopic patients might be predisposed to more severe and atypical herpes-related illness because their immune response is biased toward a TH2 cytokine profile. Human populations are infected with 8 herpesviruses, including herpes simplex virus HSV1 and HSV2 (also termed HHV1 and HHV2), varicella zoster virus (VZV or HHV3), EBV (HHV4), cytomegalovirus (HHV5), HHV6, HHV7, and Kaposi sarcoma-associated herpesvirus (termed KSV or HHV8). Herpesviruses are highly adapted to lifelong infection of their human hosts and thus can be considered a component of the human "microbiome" in addition to their role in illness triggered by primary infection. HSV1 and HSV2 infection and reactivation can present with more severe cutaneous symptoms termed eczema herpeticum in the atopic population, similar to the more severe eczema vaccinatum, and drug reaction with eosinophilia and systemic symptoms syndrome (DRESS) is associated with reactivation of HSV6 and possibly other herpesviruses in both atopic and nonatopic patients. In this review evidence is reviewed that primary infection with herpesviruses may have an atypical presentation in the atopic patient and conversely that childhood infection might alter the atopic phenotype. Reactivation of latent herpesviruses can directly alter host cytokine profiles through viral expression of cytokine-like proteins, such as IL-10 (EBV) or IL-6 (cytomegalovirus and HHV8), viral encoded and secreted siRNA and microRNAs, and modulation of expression of host transcription pathways, such as nuclear factor κB. Physicians caring for allergic and atopic populations should be aware of common and uncommon presentations of herpes-related disease in atopic patients to provide accurate diagnosis and avoid unnecessary laboratory testing or incorrect diagnosis of other conditions, such as drug allergy or autoimmune disease. Antiviral therapy and vaccines should be administered promptly when indicated clinically.}, }
@article {pmid23592793, year = {2013}, author = {Kostic, AD and Howitt, MR and Garrett, WS}, title = {Exploring host-microbiota interactions in animal models and humans.}, journal = {Genes &amp; development}, volume = {27}, number = {7}, pages = {701-718}, pmid = {23592793}, issn = {1549-5477}, support = {R01CA154426/CA/NCI NIH HHS/United States ; AI078942/AI/NIAID NIH HHS/United States ; R01 DK092405/DK/NIDDK NIH HHS/United States ; K08 AI078942/AI/NIAID NIH HHS/United States ; R01 CA154426/CA/NCI NIH HHS/United States ; F32DK098826/DK/NIDDK NIH HHS/United States ; R01 GM099537/GM/NIGMS NIH HHS/United States ; F32 DK098826/DK/NIDDK NIH HHS/United States ; GM099531/GM/NIGMS NIH HHS/United States ; R01DK092405/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Bacterial Physiological Phenomena ; Biological Evolution ; Computational Biology ; Gastrointestinal Tract/microbiology ; Humans ; Metagenome/genetics/*physiology ; *Symbiosis ; }, abstract = {The animal and bacterial kingdoms have coevolved and coadapted in response to environmental selective pressures over hundreds of millions of years. The meta'omics revolution in both sequencing and its analytic pipelines is fostering an explosion of interest in how the gut microbiome impacts physiology and propensity to disease. Gut microbiome studies are inherently interdisciplinary, drawing on approaches and technical skill sets from the biomedical sciences, ecology, and computational biology. Central to unraveling the complex biology of environment, genetics, and microbiome interaction in human health and disease is a deeper understanding of the symbiosis between animals and bacteria. Experimental model systems, including mice, fish, insects, and the Hawaiian bobtail squid, continue to provide critical insight into how host-microbiota homeostasis is constructed and maintained. Here we consider how model systems are influencing current understanding of host-microbiota interactions and explore recent human microbiome studies.}, }
@article {pmid23584251, year = {2013}, author = {Moise, L and Gutierrez, AH and Bailey-Kellogg, C and Terry, F and Leng, Q and Abdel Hady, KM and VerBerkmoes, NC and Sztein, MB and Losikoff, PT and Martin, WD and Rothman, AL and De Groot, AS}, title = {The two-faced T cell epitope: examining the host-microbe interface with JanusMatrix.}, journal = {Human vaccines &amp; immunotherapeutics}, volume = {9}, number = {7}, pages = {1577-1586}, pmid = {23584251}, issn = {2164-554X}, support = {R01-AI036525/AI/NIAID NIH HHS/United States ; R01 AI036525/AI/NIAID NIH HHS/United States ; U19 AI082642/AI/NIAID NIH HHS/United States ; AI082642/AI/NIAID NIH HHS/United States ; U19 AI082655/AI/NIAID NIH HHS/United States ; }, mesh = {Antigens, Viral/*immunology ; Computational Biology/*methods ; Cross Reactions/immunology ; Enterovirus A, Human/immunology ; Epitope Mapping ; Epitopes, T-Lymphocyte/*immunology/ultrastructure ; Hepacivirus/immunology ; Host-Pathogen Interactions/immunology ; Humans ; Receptors, Antigen, T-Cell/*immunology/ultrastructure ; }, abstract = {Advances in the field of T cell immunology have contributed to the understanding that cross-reactivity is an intrinsic characteristic of the T cell receptor (TCR), and that each TCR can potentially interact with many different T cell epitopes. To better define the potential for TCR cross-reactivity between epitopes derived from the human genome, the human microbiome, and human pathogens, we developed a new immunoinformatics tool, JanusMatrix, that represents an extension of the validated T cell epitope mapping tool, EpiMatrix. Initial explorations, summarized in this synopsis, have uncovered what appear to be important differences in the TCR cross-reactivity of selected regulatory and effector T cell epitopes with other epitopes in the human genome, human microbiome, and selected human pathogens. In addition to exploring the T cell epitope relationships between human self, commensal and pathogen, JanusMatrix may also be useful to explore some aspects of heterologous immunity and to examine T cell epitope relatedness between pathogens to which humans are exposed (Dengue serotypes, or HCV and Influenza, for example). In Hand-Foot-Mouth disease (HFMD) for example, extensive enterovirus and human microbiome cross-reactivity (and limited cross-reactivity with the human genome) seemingly predicts immunodominance. In contrast, more extensive cross-reactivity with proteins contained in the human genome as compared to the human microbiome was observed for selected Treg epitopes. While it may be impossible to predict all immune response influences, the availability of sequence data from the human genome, the human microbiome, and an array of human pathogens and vaccines has made computationally-driven exploration of the effects of T cell epitope cross-reactivity now possible. This is the first description of JanusMatrix, an algorithm that assesses TCR cross-reactivity that may contribute to a means of predicting the phenotype of T cells responding to selected T cell epitopes. Whether used for explorations of T cell phenotype or for evaluating cross-conservation between related viral strains at the TCR face of viral epitopes, further JanusMatrix studies may contribute to developing safer, more effective vaccines.}, }
@article {pmid23575749, year = {2013}, author = {Ettinger, G and Burton, JP and Reid, G}, title = {If microbial ecosystem therapy can change your life, what's the problem?.}, journal = {BioEssays : news and reviews in molecular, cellular and developmental biology}, volume = {35}, number = {6}, pages = {508-512}, doi = {10.1002/bies.201300015}, pmid = {23575749}, issn = {1521-1878}, mesh = {Administration, Rectal ; Animals ; Drug Resistance, Bacterial ; Enterocolitis, Pseudomembranous/*therapy ; Feces/*microbiology ; Humans ; Metagenome ; Ownership ; Probiotics/administration &amp; dosage ; }, abstract = {The increased incidence of morbidity and mortality due to Clostridium difficile infection, had led to the emergence of fecal microbial transplantation (FMT) as a highly successful treatment. From this, a 32 strain stool substitute has been derived, and successfully tested in a pilot human study. These approaches could revolutionize not only medical care of infectious diseases, but potentially many other conditions linked to the human microbiome. But a second revolution may be needed in order for regulatory agencies, society and medical practitioners to accept and utilize these interventions, monitor their long term effects, have a degree of control over their use, or at a minimum provide guidelines for donors and recipients.}, }
@article {pmid23574462, year = {2013}, author = {Armitage, GC}, title = {Learned and unlearned concepts in periodontal diagnostics: a 50-year perspective.}, journal = {Periodontology 2000}, volume = {62}, number = {1}, pages = {20-36}, doi = {10.1111/prd.12006}, pmid = {23574462}, issn = {1600-0757}, mesh = {History, 20th Century ; Humans ; Periodontal Diseases/*history ; Periodontics/history ; }, abstract = {In the past 50 years, conceptual changes in the field of periodontal diagnostics have paralleled those associated with a better scientific understanding of the full spectrum of processes that affect periodontal health and disease. Fifty years ago, concepts regarding the diagnosis of periodontal diseases followed the classical pathology paradigm. It was believed that the two basic forms of destructive periodontal disease were chronic inflammatory periodontitis and 'periodontosis'- a degenerative condition. In the subsequent 25 years it was shown that periodontosis was an infection. By 1987, major new concepts regarding the diagnosis and pathogenesis of periodontitis included: (i) all cases of untreated gingivitis do not inevitably progress to periodontitis; (ii) progression of untreated periodontitis is often episodic; (iii) some sites with untreated periodontitis do not progress; (iv) a rather small population of specific bacteria ('periodontal pathogens') appear to be the main etiologic agents of chronic inflammatory periodontitis; and (v) tissue damage in periodontitis is primarily caused by inflammatory and immunologic host responses to infecting agents. The concepts that were in place by 1987 are still largely intact in 2012. However, in the decades to come, it is likely that new information on the human microbiome will change our current concepts concerning the prevention, diagnosis and treatment of periodontal diseases.}, }
@article {pmid23566633, year = {2013}, author = {Fortenberry, JD}, title = {The uses of race and ethnicity in human microbiome research.}, journal = {Trends in microbiology}, volume = {21}, number = {4}, pages = {165-166}, doi = {10.1016/j.tim.2013.01.001}, pmid = {23566633}, issn = {1878-4380}, mesh = {*Ethnicity ; Humans ; *Metagenome ; *Racial Groups ; }, abstract = {Research on the human microbiome is beginning to address factors associated with between-group differences. Recognition of the social and political nature of traditional race and ethnicity categories will allow microbiome research to contribute to reduction of health disparities while avoiding attribution of causal inference to specific race and ethnicity categories.}, }
@article {pmid23565326, year = {2013}, author = {Cugini, C and Klepac-Ceraj, V and Rackaityte, E and Riggs, JE and Davey, ME}, title = {Porphyromonas gingivalis: keeping the pathos out of the biont.}, journal = {Journal of oral microbiology}, volume = {5}, number = {}, pages = {}, pmid = {23565326}, issn = {2000-2297}, support = {F32 DE022484/DE/NIDCR NIH HHS/United States ; R01 DE019117/DE/NIDCR NIH HHS/United States ; R15 CA136901/CA/NCI NIH HHS/United States ; }, abstract = {The primary goal of the human microbiome initiative has been to increase our understanding of the structure and function of our indigenous microbiota and their effects on human health and predisposition to disease. Because of its clinical importance and accessibility for in vivo study, the oral biofilm is one of the best-understood microbial communities associated with the human body. Studies have shown that there is a succession of select microbial interactions that directs the maturation of a defined community structure, generating the formation of dental plaque. Although the initiating factors that lead to disease development are not clearly defined, in many individuals there is a fundamental shift from a health-associated biofilm community to one that is pathogenic in nature and a central player in the pathogenic potential of this community is the presence of Porphyromonas gingivalis. This anaerobic bacterium is a natural member of the oral microbiome, yet it can become highly destructive (termed pathobiont) and proliferate to high cell numbers in periodontal lesions, which is attributed to its arsenal of specialized virulence factors. Hence, this organism is regarded as a primary etiologic agent of periodontal disease progression. In this review, we summarize some of the latest information regarding what is known about its role in periodontitis, including pathogenic potential as well as ecological and nutritional parameters that may shift this commensal to a virulent state. We also discuss parallels between the development of pathogenic biofilms and the human cellular communities that lead to cancer, specifically we frame our viewpoint in the context of 'wounds that fail to heal'.}, }
@article {pmid23563424, year = {2013}, author = {Brown, J and de Vos, WM and DiStefano, PS and Doré, J and Huttenhower, C and Knight, R and Lawley, TD and Raes, J and Turnbaugh, P}, title = {Translating the human microbiome.}, journal = {Nature biotechnology}, volume = {31}, number = {4}, pages = {304-308}, pmid = {23563424}, issn = {1546-1696}, mesh = {Animals ; Biomarkers/metabolism ; Computational Biology ; Disease ; Disease Susceptibility ; High-Throughput Nucleotide Sequencing ; Humans ; Metagenome/*genetics ; Sequence Analysis, DNA ; *Translational Research, Biomedical ; }, }
@article {pmid23550823, year = {2013}, author = {Maurice, CF and Turnbaugh, PJ}, title = {Quantifying the metabolic activities of human-associated microbial communities across multiple ecological scales.}, journal = {FEMS microbiology reviews}, volume = {37}, number = {5}, pages = {830-848}, pmid = {23550823}, issn = {1574-6976}, support = {P50 GM068763/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Ecosystem ; Humans ; Metabolomics/*methods ; *Metagenome ; Metagenomics/*methods ; *Microbiota ; Single-Cell Analysis/methods ; }, abstract = {Humans are home to complex microbial communities, whose aggregate genomes and their encoded metabolic activities are referred to as the human microbiome. Recently, researchers have begun to appreciate that different human body habitats and the activities of their resident microorganisms can be better understood in ecological terms, as a range of spatial scales encompassing single cells, guilds of microorganisms responsive to a similar substrate, microbial communities, body habitats, and host populations. However, the bulk of the work to date has focused on studies of culturable microorganisms in isolation or on DNA sequencing-based surveys of microbial diversity in small-to-moderate-sized cohorts of individuals. Here, we discuss recent work that highlights the potential for assessing the human microbiome at a range of spatial scales, and for developing novel techniques that bridge multiple levels: for example, through the combination of single-cell methods and metagenomic sequencing. These studies promise to not only provide a much-needed epidemiological and ecological context for mechanistic studies of culturable and genetically tractable microorganisms, but may also lead to the discovery of fundamental rules that govern the assembly and function of host-associated microbial communities.}, }
@article {pmid23540701, year = {2013}, author = {MacNeil, LT and Watson, E and Arda, HE and Zhu, LJ and Walhout, AJ}, title = {Diet-induced developmental acceleration independent of TOR and insulin in C. elegans.}, journal = {Cell}, volume = {153}, number = {1}, pages = {240-252}, pmid = {23540701}, issn = {1097-4172}, support = {P40 OD010440/OD/NIH HHS/United States ; R56 DK068429/DK/NIDDK NIH HHS/United States ; DK068429/DK/NIDDK NIH HHS/United States ; /CAPMC/CIHR/Canada ; R01 DK068429/DK/NIDDK NIH HHS/United States ; }, mesh = {Acyl-CoA Dehydrogenase/metabolism ; Animals ; Betaproteobacteria ; Caenorhabditis elegans/metabolism/*physiology ; Caenorhabditis elegans Proteins/*metabolism ; Diet ; Escherichia coli ; Gene Expression ; Insulin/*metabolism ; Longevity ; Molting ; Phosphotransferases (Alcohol Group Acceptor)/*metabolism ; Receptors, Cytoplasmic and Nuclear/metabolism ; Starvation ; Transcriptome ; }, abstract = {Dietary composition has major effects on physiology. Here, we show that developmental rate, reproduction, and lifespan are altered in C. elegans fed Comamonas DA1877 relative to those fed a standard E. coli OP50 diet. We identify a set of genes that change in expression in response to this diet and use the promoter of one of these (acdh-1) as a dietary sensor. Remarkably, the effects on transcription and development occur even when Comamonas DA1877 is diluted with another diet, suggesting that Comamonas DA1877 generates a signal that is sensed by the nematode. Surprisingly, the developmental effect is independent from TOR and insulin signaling. Rather, Comamonas DA1877 affects cyclic gene expression during molting, likely through the nuclear hormone receptor NHR-23. Altogether, our findings indicate that different bacteria elicit various responses via distinct mechanisms, which has implications for diseases such as obesity and the interactions between the human microbiome and intestinal cells.}, }
@article {pmid23539678, year = {2013}, author = {Wang, ZK and Yang, YS}, title = {Upper gastrointestinal microbiota and digestive diseases.}, journal = {World journal of gastroenterology}, volume = {19}, number = {10}, pages = {1541-1550}, pmid = {23539678}, issn = {2219-2840}, mesh = {Animals ; *Bacteria/classification/genetics/growth &amp; development ; Gastrointestinal Diseases/*microbiology ; Gastrointestinal Tract/*microbiology ; Gene Expression Regulation, Bacterial ; Genome, Bacterial ; Host-Pathogen Interactions ; Humans ; Metagenomics/methods ; Risk Factors ; }, abstract = {Metagenomics which combines the power of genomics, bioinformatics, and systems biology, provide new access to the microbial world. Metagenomics permit the genetic analysis of complex microbial populations without requiring prior cultivation. Through the conceptual innovations in metagenomics and the improvements in DNA high-throughput sequencing and bioinformatics analysis technology, gastrointestinal microbiology has entered the metagenomics era and become a hot topic worldwide. Human microbiome research is underway, however, most studies in this area have focused on the composition and function of the intestinal microbiota and the relationship between intestinal microbiota and metabolic diseases (obesity, diabetes, metabolic syndrome, etc.) and intestinal disorders [inflammatory bowel disease, colorectal cancer, irritable bowel syndrome (IBS), etc.]. Few investigations on microbiota have been conducted within the upper gastrointestinal tract (esophagus, stomach and duodenum). The upper gastrointestinal microbiota is essential for several gastrointestinal illnesses, including esophagitis, Barrett's esophagus, and esophageal carcinoma, gastritis and gastric cancer, small intestinal bacterial overgrowth, IBS and celiac disease. However, the constitution and diversity of the microbiota in different sections of the upper gastrointestinal tract under health and various disease states, as well as the function of microbiota in the pathogenesis of various digestive diseases are still undefined. The current article provides an overview of the recent findings regarding the relationship between upper gastrointestinal microbiota and gastrointestinal diseases; and discusses the study limitations and future directions of upper gastrointestinal microbiota research.}, }
@article {pmid23519420, year = {2013}, author = {Michalska, K and Tan, K and Li, H and Hatzos-Skintges, C and Bearden, J and Babnigg, G and Joachimiak, A}, title = {GH1-family 6-P-β-glucosidases from human microbiome lactic acid bacteria.}, journal = {Acta crystallographica. Section D, Biological crystallography}, volume = {69}, number = {Pt 3}, pages = {451-463}, pmid = {23519420}, issn = {1399-0047}, support = {U54 GM094585/GM/NIGMS NIH HHS/United States ; GM094585/GM/NIGMS NIH HHS/United States ; }, mesh = {Crystallography, X-Ray ; Glucosidases/*chemistry/genetics/metabolism ; Humans ; Lactobacillus plantarum/*enzymology/genetics/metabolism ; Ligands ; *Metagenome ; Phosphoenolpyruvate Sugar Phosphotransferase System/*chemistry ; Streptococcus mutans/*enzymology/genetics ; }, abstract = {In lactic acid bacteria and other bacteria, carbohydrate uptake is mostly governed by phosphoenolpyruvate-dependent phosphotransferase systems (PTSs). PTS-dependent translocation through the cell membrane is coupled with phosphorylation of the incoming sugar. After translocation through the bacterial membrane, the β-glycosidic bond in 6'-P-β-glucoside is cleaved, releasing 6-P-β-glucose and the respective aglycon. This reaction is catalyzed by 6-P-β-glucosidases, which belong to two glycoside hydrolase (GH) families: GH1 and GH4. Here, the high-resolution crystal structures of GH1 6-P-β-glucosidases from Lactobacillus plantarum (LpPbg1) and Streptococcus mutans (SmBgl) and their complexes with ligands are reported. Both enzymes show hydrolytic activity towards 6'-P-β-glucosides. The LpPbg1 structure has been determined in an apo form as well as in a complex with phosphate and a glucose molecule corresponding to the aglycon molecule. The S. mutans homolog contains a sulfate ion in the phosphate-dedicated subcavity. SmBgl was also crystallized in the presence of the reaction product 6-P-β-glucose. For a mutated variant of the S. mutans enzyme (E375Q), the structure of a 6'-P-salicin complex has also been determined. The presence of natural ligands enabled the definition of the structural elements that are responsible for substrate recognition during catalysis.}, }
@article {pmid23509275, year = {2013}, author = {Campbell, JH and O'Donoghue, P and Campbell, AG and Schwientek, P and Sczyrba, A and Woyke, T and Söll, D and Podar, M}, title = {UGA is an additional glycine codon in uncultured SR1 bacteria from the human microbiota.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {110}, number = {14}, pages = {5540-5545}, pmid = {23509275}, issn = {1091-6490}, support = {R01 GM022854/GM/NIGMS NIH HHS/United States ; R01 HG004857/HG/NHGRI NIH HHS/United States ; R37 GM022854/GM/NIGMS NIH HHS/United States ; GM22854/GM/NIGMS NIH HHS/United States ; }, mesh = {Bacteria/*genetics ; Base Sequence ; Codon, Terminator/*genetics ; Flow Cytometry ; Genetic Code/*genetics ; Genetic Variation ; Glycine/*genetics ; Humans ; Metagenome/*genetics ; Molecular Sequence Data ; Mouth/*microbiology ; Nucleic Acid Amplification Techniques ; Sequence Analysis, DNA ; }, abstract = {The composition of the human microbiota is recognized as an important factor in human health and disease. Many of our cohabitating microbes belong to phylum-level divisions for which there are no cultivated representatives and are only represented by small subunit rRNA sequences. For one such taxon (SR1), which includes bacteria with elevated abundance in periodontitis, we provide a single-cell genome sequence from a healthy oral sample. SR1 bacteria use a unique genetic code. In-frame TGA (opal) codons are found in most genes (85%), often at loci normally encoding conserved glycine residues. UGA appears not to function as a stop codon and is in equilibrium with the canonical GGN glycine codons, displaying strain-specific variation across the human population. SR1 encodes a divergent tRNA(Gly)UCA with an opal-decoding anticodon. SR1 glycyl-tRNA synthetase acylates tRNA(Gly)UCA with glycine in vitro with similar activity compared with normal tRNA(Gly)UCC. Coexpression of SR1 glycyl-tRNA synthetase and tRNA(Gly)UCA in Escherichia coli yields significant β-galactosidase activity in vivo from a lacZ gene containing an in-frame TGA codon. Comparative genomic analysis with Human Microbiome Project data revealed that the human body harbors a striking diversity of SR1 bacteria. This is a surprising finding because SR1 is most closely related to bacteria that live in anoxic and thermal environments. Some of these bacteria share common genetic and metabolic features with SR1, including UGA to glycine reassignment and an archaeal-type ribulose-1,5-bisphosphate carboxylase (RubisCO) involved in AMP recycling. UGA codon reassignment renders SR1 genes untranslatable by other bacteria, which impacts horizontal gene transfer within the human microbiota.}, }
@article {pmid23505415, year = {2013}, author = {Matsen, FA and Evans, SN}, title = {Edge principal components and squash clustering: using the special structure of phylogenetic placement data for sample comparison.}, journal = {PloS one}, volume = {8}, number = {3}, pages = {e56859}, pmid = {23505415}, issn = {1932-6203}, support = {R01 HG005966/HG/NHGRI NIH HHS/United States ; HG005966-01/HG/NHGRI NIH HHS/United States ; }, mesh = {Algorithms ; *Cluster Analysis ; Environmental Microbiology ; Female ; Humans ; Metagenome/genetics ; *Phylogeny ; *Principal Component Analysis ; Vagina/microbiology ; }, abstract = {Principal components analysis (PCA) and hierarchical clustering are two of the most heavily used techniques for analyzing the differences between nucleic acid sequence samples taken from a given environment. They have led to many insights regarding the structure of microbial communities. We have developed two new complementary methods that leverage how this microbial community data sits on a phylogenetic tree. Edge principal components analysis enables the detection of important differences between samples that contain closely related taxa. Each principal component axis is a collection of signed weights on the edges of the phylogenetic tree, and these weights are easily visualized by a suitable thickening and coloring of the edges. Squash clustering outputs a (rooted) clustering tree in which each internal node corresponds to an appropriate "average" of the original samples at the leaves below the node. Moreover, the length of an edge is a suitably defined distance between the averaged samples associated with the two incident nodes, rather than the less interpretable average of distances produced by UPGMA, the most widely used hierarchical clustering method in this context. We present these methods and illustrate their use with data from the human microbiome.}, }
@article {pmid23493677, year = {2013}, author = {Fitzsimons, MS and Novotny, M and Lo, CC and Dichosa, AE and Yee-Greenbaum, JL and Snook, JP and Gu, W and Chertkov, O and Davenport, KW and McMurry, K and Reitenga, KG and Daughton, AR and He, J and Johnson, SL and Gleasner, CD and Wills, PL and Parson-Quintana, B and Chain, PS and Detter, JC and Lasken, RS and Han, CS}, title = {Nearly finished genomes produced using gel microdroplet culturing reveal substantial intraspecies genomic diversity within the human microbiome.}, journal = {Genome research}, volume = {23}, number = {5}, pages = {878-888}, pmid = {23493677}, issn = {1549-5469}, support = {HHSN272200900007C/AI/NIAID NIH HHS/United States ; R01 HG003647/HG/NHGRI NIH HHS/United States ; U54 AI084844/AI/NIAID NIH HHS/United States ; U54 AI-084844-01/AI/NIAID NIH HHS/United States ; }, mesh = {Bacteria/*genetics ; *Genetic Variation ; Genome, Bacterial/*genetics ; Genomics ; Humans ; *Microbiota ; Polymerase Chain Reaction ; Polymorphism, Single Nucleotide ; Sequence Analysis, DNA/methods ; }, abstract = {The majority of microbial genomic diversity remains unexplored. This is largely due to our inability to culture most microorganisms in isolation, which is a prerequisite for traditional genome sequencing. Single-cell sequencing has allowed researchers to circumvent this limitation. DNA is amplified directly from a single cell using the whole-genome amplification technique of multiple displacement amplification (MDA). However, MDA from a single chromosome copy suffers from amplification bias and a large loss of specificity from even very small amounts of DNA contamination, which makes assembling a genome difficult and completely finishing a genome impossible except in extraordinary circumstances. Gel microdrop cultivation allows culturing of a diverse microbial community and provides hundreds to thousands of genetically identical cells as input for an MDA reaction. We demonstrate the utility of this approach by comparing sequencing results of gel microdroplets and single cells following MDA. Bias is reduced in the MDA reaction and genome sequencing, and assembly is greatly improved when using gel microdroplets. We acquired multiple near-complete genomes for two bacterial species from human oral and stool microbiome samples. A significant amount of genome diversity, including single nucleotide polymorphisms and genome recombination, is discovered. Gel microdroplets offer a powerful and high-throughput technology for assembling whole genomes from complex samples and for probing the pan-genome of naturally occurring populations.}, }
@article {pmid23487774, year = {2013}, author = {Berry, D and Stecher, B and Schintlmeister, A and Reichert, J and Brugiroux, S and Wild, B and Wanek, W and Richter, A and Rauch, I and Decker, T and Loy, A and Wagner, M}, title = {Host-compound foraging by intestinal microbiota revealed by single-cell stable isotope probing.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {110}, number = {12}, pages = {4720-4725}, pmid = {23487774}, issn = {1091-6490}, support = {294343/ERC_/European Research Council/International ; }, mesh = {Animals ; Bacteroides/*physiology ; *Ecosystem ; Humans ; Intestines/*microbiology ; Isotope Labeling ; Metagenome/*physiology ; Mice ; }, abstract = {The animal and human intestinal mucosa secretes an assortment of compounds to establish a physical barrier between the host tissue and intestinal contents, a separation that is vital for health. Some pathogenic microorganisms as well as members of the commensal intestinal microbiota have been shown to be able to break down these secreted compounds. Our understanding of host-compound degradation by the commensal microbiota has been limited to knowledge about simplified model systems because of the difficulty in studying the complex intestinal ecosystem in vivo. In this study, we introduce an approach that overcomes previous technical limitations and allows us to observe which microbial cells in the intestine use host-derived compounds. We added stable isotope-labeled threonine i.v. to mice and combined fluorescence in situ hybridization with high-resolution secondary ion mass spectrometry imaging to characterize utilization of host proteins by individual bacterial cells. We show that two bacterial species, Bacteroides acidifaciens and Akkermansia muciniphila, are important host-protein foragers in vivo. Using gnotobiotic mice we show that microbiota composition determines the magnitude and pattern of foraging by these organisms, demonstrating that a complex microbiota is necessary in order for this niche to be fully exploited. These results underscore the importance of in vivo studies of intestinal microbiota, and the approach presented in this study will be a powerful tool to address many other key questions in animal and human microbiome research.}, }
@article {pmid23444796, year = {2012}, author = {Błaszkowska, J and Wójcik, A}, title = {Current problems concerning parasitology and mycology with regard to diseases of the skin and its appendages.}, journal = {Annals of parasitology}, volume = {58}, number = {3}, pages = {111-123}, pmid = {23444796}, issn = {2299-0631}, mesh = {Animals ; Dermatomycoses/diagnosis/epidemiology/therapy/transmission ; Humans ; Mycoses/*diagnosis/epidemiology/*therapy/transmission ; Parasitic Diseases/*diagnosis/epidemiology/*therapy/transmission ; Zoonoses/microbiology/parasitology/transmission ; }, abstract = {Current issues concerning Parasitology and Mycology with regard to diseases of the skin and its appendages are presented. Aspects of diagnostics, clinical picture and therapy of skin and nail mycoses, as well as difficulties in the diagnosis and treatment of both native parasitoses (toxoplasmosis) and imported human tropical parasitoses (malaria, filariosis) have been emphasised. The clinical importance of environmental mould fungi in nosocomial infections and fungal meningitis, as well as selected properties of fungi isolated from patients with head and neck neoplasms treated by radiotherapy are discussed. Other mycological topics include the characteristics of newly-synthesized thiosemicarbazides and thiadiazoles as potential drugs against toxoplasmosis and their biological activity against Toxoplasma gondii tachyzoites, selected molecular mechanisms of resistance to azoles, Candida albicans strains and a new tool (barcoding DNA) for describing the biodiversity of potential allergenic molds. The importance of environmental factors in pathogenesis of mycoses and parasitoses is noted. The characteristics of pathogenic fungi isolated from natural ponds in Bialystok and potentially pathogenic yeast-like fungi isolated from children's recreation areas in Lodz are presented. The ongoing problem of anthropozoonoses is considered, as are the roles of stray cats and dogs in contaminating soil with the developing forms of intestinal parasites. The characteristics of the human microbiome, including population composition, activity and their importance in normal human physiology, are presented, as are the major goals of the Human Microbiome Project initiated by National Institutes of Health (NIH).}, }
@article {pmid23439321, year = {2013}, author = {Mick, E and Stern, A and Sorek, R}, title = {Holding a grudge: persisting anti-phage CRISPR immunity in multiple human gut microbiomes.}, journal = {RNA biology}, volume = {10}, number = {5}, pages = {900-906}, pmid = {23439321}, issn = {1555-8584}, mesh = {Adult ; Archaea/genetics ; Bacteria/*genetics/*virology ; Bacteriophages/*genetics/physiology ; CRISPR-Associated Proteins/genetics/*metabolism ; *Clustered Regularly Interspaced Short Palindromic Repeats ; DNA, Intergenic ; Female ; Gastrointestinal Tract/*microbiology ; Gene Targeting ; Humans ; Lysogeny ; Male ; Metagenomics ; *Microbiota ; Middle Aged ; }, abstract = {The CRISPR (clustered regularly interspaced short palindromic repeats)/Cas (CRISPR-associated) system of bacteria and archaea constitutes a mechanism of acquired adaptive immunity against phages, which is based on genome-encoded markers of previously infecting phage sequences ("spacers"). As a repository of phage sequences, these spacers make the system particularly suitable for elucidating phage-bacteria interactions in metagenomic studies. Recent metagenomic analyses of CRISPRs associated with the human microbiome intriguingly revealed conserved "memory spacers" shared by bacteria in multiple unrelated, geographically separated individuals. Here, we discuss possible avenues for explaining this phenomenon by integrating insights from CRISPR biology and phage-bacteria ecology, with a special focus on the human gut. We further explore the growing body of evidence for the role of CRISPR/Cas in regulating the interplay between bacteria and lysogenic phages, which may be intimately related to the presence of memory spacers and sheds new light on the multifaceted biological and ecological modes of action of CRISPR/Cas.}, }
@article {pmid23437130, year = {2013}, author = {Jensen, A and Fagö-Olsen, H and Sørensen, CH and Kilian, M}, title = {Molecular mapping to species level of the tonsillar crypt microbiota associated with health and recurrent tonsillitis.}, journal = {PloS one}, volume = {8}, number = {2}, pages = {e56418}, pmid = {23437130}, issn = {1932-6203}, mesh = {Adolescent ; Adult ; Base Sequence ; Biodiversity ; Child, Preschool ; Female ; Genetic Variation ; *Health ; Humans ; Male ; Metagenome/*genetics ; Palatine Tonsil/*microbiology/*pathology ; Principal Component Analysis ; Recurrence ; Species Specificity ; Tonsillitis/*microbiology/*pathology ; Young Adult ; }, abstract = {The human palatine tonsils, which belong to the central antigen handling sites of the mucosal immune system, are frequently affected by acute and recurrent infections. This study compared the microbiota of the tonsillar crypts in children and adults affected by recurrent tonsillitis with that of healthy adults and children with tonsillar hyperplasia. An in-depth 16S rRNA gene based pyrosequencing approach combined with a novel strategy that included phylogenetic analysis and detection of species-specific sequence signatures enabled identification of the major part of the microbiota to species level. A complex microbiota consisting of between 42 and 110 taxa was demonstrated in both children and adults. This included a core microbiome of 12 abundant genera found in all samples regardless of age and health status. Yet, Haemophilus influenzae, Neisseria species, and Streptococcus pneumoniae were almost exclusively detected in children. In contrast, Streptococcus pseudopneumoniae was present in all samples. Obligate anaerobes like Porphyromonas, Prevotella, and Fusobacterium were abundantly present in children, but the species diversity of Porphyromonas and Prevotella was larger in adults and included species that are considered putative pathogens in periodontal diseases, i.e. Porphyromonas gingivalis, Porphyromonas endodontalis, and Tannerella forsythia. Unifrac analysis showed that recurrent tonsillitis is associated with a shift in the microbiota of the tonsillar crypts. Fusobacterium necrophorum, Streptococcus intermedius and Prevotella melaninogenica/histicola were associated with recurrent tonsillitis in adults, whereas species traditionally associated with acute tonsillitis like pyogenic streptococci and Staphylococcus aureus were scarce. The findings suggest that recurrent tonsillitis is a polymicrobial infection in which interactions within consortia of taxa play an etiologic role. The study contributes to the human microbiome data, to the understanding of the etiology of infections affecting the tonsils, and forms a basis for further insight into the consequences of the intense microbe-host interactions that take place in the tonsils.}, }
@article {pmid23431991, year = {2013}, author = {Bakhtiar, SM and LeBlanc, JG and Salvucci, E and Ali, A and Martin, R and Langella, P and Chatel, JM and Miyoshi, A and Bermúdez-Humarán, LG and Azevedo, V}, title = {Implications of the human microbiome in inflammatory bowel diseases.}, journal = {FEMS microbiology letters}, volume = {342}, number = {1}, pages = {10-17}, doi = {10.1111/1574-6968.12111}, pmid = {23431991}, issn = {1574-6968}, mesh = {*Biota ; High-Throughput Nucleotide Sequencing ; Humans ; Inflammatory Bowel Diseases/*microbiology ; *Metagenome ; }, abstract = {The study of the human microbiome or community of microorganisms and collection of genomes found in the human body is one of the fastest growing research areas because many diseases are reported to be associated with microbiome imbalance or dysbiosis. With the improvement in novel sequencing techniques, researchers are now generating millions of sequences of different sites from the human body and evaluating specific differences in microbial communities. The importance of microbiome constituency is so relevant that several consortia like the Human Microbiome project (HMP) and Metagenomics of the Human Intestinal Tract (MetaHIT) project are focusing mainly on the human microbiome. The aim of this review is to highlight points of research in this field, mainly focusing on particular factors that modulate the microbiome and important insights into its potential impact on our health and well-being.}, }
@article {pmid23431268, year = {2013}, author = {Marx, CJ}, title = {Can you sequence ecology? Metagenomics of adaptive diversification.}, journal = {PLoS biology}, volume = {11}, number = {2}, pages = {e1001487}, pmid = {23431268}, issn = {1545-7885}, mesh = {Biological Evolution ; *Ecology ; Metagenomics/*methods ; }, abstract = {Few areas of science have benefited more from the expansion in sequencing capability than the study of microbial communities. Can sequence data, besides providing hypotheses of the functions the members possess, detect the evolutionary and ecological processes that are occurring? For example, can we determine if a species is adapting to one niche, or if it is diversifying into multiple specialists that inhabit distinct niches? Fortunately, adaptation of populations in the laboratory can serve as a model to test our ability to make such inferences about evolution and ecology from sequencing. Even adaptation to a single niche can give rise to complex temporal dynamics due to the transient presence of multiple competing lineages. If there are multiple niches, this complexity is augmented by segmentation of the population into multiple specialists that can each continue to evolve within their own niche. For a known example of parallel diversification that occurred in the laboratory, sequencing data gave surprisingly few obvious, unambiguous signs of the ecological complexity present. Whereas experimental systems are open to direct experimentation to test hypotheses of selection or ecological interaction, the difficulty in "seeing ecology" from sequencing for even such a simple system suggests translation to communities like the human microbiome will be quite challenging. This will require both improved empirical methods to enhance the depth and time resolution for the relevant polymorphisms and novel statistical approaches to rigorously examine time-series data for signs of various evolutionary and ecological phenomena within and between species.}, }
@article {pmid23418187, year = {2013}, author = {Klingenberg, H and Aßhauer, KP and Lingner, T and Meinicke, P}, title = {Protein signature-based estimation of metagenomic abundances including all domains of life and viruses.}, journal = {Bioinformatics (Oxford, England)}, volume = {29}, number = {8}, pages = {973-980}, pmid = {23418187}, issn = {1367-4811}, mesh = {DNA, Archaeal/analysis ; DNA, Viral/analysis ; Humans ; Metagenome ; Metagenomics/*methods ; Phylogeny ; *Protein Structure, Tertiary ; }, abstract = {MOTIVATION: Metagenome analysis requires tools that can estimate the taxonomic abundances in anonymous sequence data over the whole range of biological entities. Because there is usually no prior knowledge about the data composition, not only all domains of life but also viruses have to be included in taxonomic profiling. Such a full-range approach, however, is difficult to realize owing to the limited coverage of available reference data. In particular, archaea and viruses are generally not well represented by current genome databases.<br><br>RESULTS: We introduce a novel approach to taxonomic profiling of metagenomes that is based on mixture model analysis of protein signatures. Our results on simulated and real data reveal the difficulties of the existing methods when measuring achaeal or viral abundances and show the overall good profiling performance of the protein-based mixture model. As an application example, we provide a large-scale analysis of data from the Human Microbiome Project. This demonstrates the utility of our method as a first instance profiling tool for a fast estimate of the community structure.<br><br>AVAILABILITY: http://gobics.de/TaxyPro.<br><br>SUPPLEMENTARY INFORMATION: Supplementary Material is available at Bioinformatics online.}, }
@article {pmid23409037, year = {2013}, author = {Ballarini, A and Segata, N and Huttenhower, C and Jousson, O}, title = {Simultaneous quantification of multiple bacteria by the BactoChip microarray designed to target species-specific marker genes.}, journal = {PloS one}, volume = {8}, number = {2}, pages = {e55764}, pmid = {23409037}, issn = {1932-6203}, support = {R01 HG005969/HG/NHGRI NIH HHS/United States ; 1R01HG005969/HG/NHGRI NIH HHS/United States ; }, mesh = {Bacteria/*classification/*genetics ; *Genes, Bacterial ; Humans ; Metagenome ; Mouth/microbiology ; *Oligonucleotide Array Sequence Analysis/methods ; Reproducibility of Results ; Sensitivity and Specificity ; }, abstract = {Bacteria are ubiquitous throughout the environment, the most abundant inhabitants of the healthy human microbiome, and causal pathogens in a variety of diseases. Their identification in disease is often an essential step in rapid diagnosis and targeted intervention, particularly in clinical settings. At present, clinical bacterial detection and discrimination is primarily culture-based, requiring both time and microbiological expertise, especially for bacteria that are not easily cultivated. Higher-throughput molecular methods based on PCR amplification or, recently, microarrays are reaching the clinic as well. However, these methods are currently restricted to a small set of microbes or based on conserved phylogenetic markers such as the 16S rRNA gene, which are difficult to resolve at the species or strain levels. Here, we designed and experimentally validated the BactoChip, an oligonucleotide microarray for bacterial detection and quantification. The chip allows the culture-independent identification of bacterial species, also determining their relative abundances in complex communities as occur in the commensal microbiota or in clinical settings. The microarray successfully distinguished among bacterial species from 21 different genera using 60-mer probes targeting a novel set of in silico identified high-resolution marker genes. The BactoChip additionally proved accurate in determining species-level relative abundances over a 100-fold dynamic range in complex bacterial communities and with a low limit of detection (0.1%). In combination with the continually increasing number of sequenced bacterial genomes, future iterations of the technology could enable to highly accurate clinically-oriented tools for rapid assessment of bacterial community composition and relative abundances.}, }
@article {pmid23408395, year = {2012}, author = {Mead, DA and Lucas, S and Copeland, A and Lapidus, A and Cheng, JF and Bruce, DC and Goodwin, LA and Pitluck, S and Chertkov, O and Zhang, X and Detter, JC and Han, CS and Tapia, R and Land, M and Hauser, LJ and Chang, YJ and Kyrpides, NC and Ivanova, NN and Ovchinnikova, G and Woyke, T and Brumm, C and Hochstein, R and Schoenfeld, T and Brumm, P}, title = {Complete Genome Sequence of Paenibacillus strain Y4.12MC10, a Novel Paenibacillus lautus strain Isolated from Obsidian Hot Spring in Yellowstone National Park.}, journal = {Standards in genomic sciences}, volume = {6}, number = {3}, pages = {381-400}, pmid = {23408395}, issn = {1944-3277}, abstract = {Paenibacillus sp.Y412MC10 was one of a number of organisms isolated from Obsidian Hot Spring, Yellowstone National Park, Montana, USA under permit from the National Park Service. The isolate was initially classified as a Geobacillus sp. Y412MC10 based on its isolation conditions and similarity to other organisms isolated from hot springs at Yellowstone National Park. Comparison of 16 S rRNA sequences within the Bacillales indicated that Geobacillus sp.Y412MC10 clustered with Paenibacillus species, and the organism was most closely related to Paenibacillus lautus. Lucigen Corp. prepared genomic DNA and the genome was sequenced, assembled, and annotated by the DOE Joint Genome Institute. The genome sequence was deposited at the NCBI in October 2009 (NC_013406). The genome of Paenibacillus sp. Y412MC10 consists of one circular chromosome of 7,121,665 bp with an average G+C content of 51.2%. Comparison to other Paenibacillus species shows the organism lacks nitrogen fixation, antibiotic production and social interaction genes reported in other paenibacilli. The Y412MC10 genome shows a high level of synteny and homology to the draft sequence of Paenibacillus sp. HGF5, an organism from the Human Microbiome Project (HMP) Reference Genomes. This, combined with genomic CAZyme analysis, suggests an intestinal, rather than environmental origin for Y412MC10.}, }
@article {pmid23406581, year = {2013}, author = {Renko, J and Koskela, KA and Lepp, PW and Oksala, N and Levula, M and Lehtimäki, T and Solakivi, T and Kunnas, T and Nikkari, S and Nikkari, ST}, title = {Bacterial DNA signatures in carotid atherosclerosis represent both commensals and pathogens of skin origin.}, journal = {European journal of dermatology : EJD}, volume = {23}, number = {1}, pages = {53-58}, doi = {10.1684/ejd.2012.1908}, pmid = {23406581}, issn = {1952-4013}, mesh = {Actinobacteria/*isolation &amp; purification ; Aged ; Aged, 80 and over ; Carotid Artery Diseases/*microbiology ; DNA, Bacterial/*isolation &amp; purification ; DNA, Ribosomal ; Female ; Humans ; Male ; *Metagenome ; Middle Aged ; Polymerase Chain Reaction ; Sequence Analysis, DNA ; Skin/*microbiology ; }, abstract = {Infectious agents have been suggested to be involved in atherosclerosis. By using a novel subtraction broad-range PCR approach, we defined bacterial DNA signatures in surgically removed sterile carotid artery endarterectomy plaques of patients with carotid atherosclerosis. Eighty partial bacterial 16S rDNA nucleotide sequences from eight patients were studied. Furthermore, 34 clones representing 21 bacterial sequence-types from the reagents used for DNA extraction and PCR amplification were determined. After subtraction of these potential methodological contaminants, 23 bacterial sequence-types were considered as clinically relevant findings. The most prominent phylum, Actinobacteria, accounted for 74% of these relevant sequences. Furthermore, according to the Human Microbiome project database, interestingly, nearly all (94%) of the sequences were associated with the human skin microbiome.}, }
@article {pmid23401286, year = {2013}, author = {Devaraj, S and Hemarajata, P and Versalovic, J}, title = {The human gut microbiome and body metabolism: implications for obesity and diabetes.}, journal = {Clinical chemistry}, volume = {59}, number = {4}, pages = {617-628}, pmid = {23401286}, issn = {1530-8561}, support = {R01 DK065075-01/DK/NIDDK NIH HHS/United States ; UH3 DK083990/DK/NIDDK NIH HHS/United States ; P30 DK56338-06A2/DK/NIDDK NIH HHS/United States ; R01 DK065075/DK/NIDDK NIH HHS/United States ; R01 AT004326-01A1/AT/NCCIH NIH HHS/United States ; P30 DK056338/DK/NIDDK NIH HHS/United States ; R01 AT004326/AT/NCCIH NIH HHS/United States ; }, mesh = {Amino Acids/metabolism ; Animals ; Carbohydrate Metabolism ; Diabetes Mellitus/metabolism/*microbiology ; Humans ; Intestinal Mucosa/metabolism ; Intestines/*microbiology ; *Metagenome ; Obesity/*microbiology ; }, abstract = {BACKGROUND: Obesity, metabolic syndrome, and type 2 diabetes are major public health challenges. Recently, interest has surged regarding the possible role of the intestinal microbiota as potential novel contributors to the increased prevalence of these 3 disorders.<br><br>CONTENT: Recent advances in microbial DNA sequencing technologies have resulted in the widespread application of whole-genome sequencing technologies for metagenomic DNA analysis of complex ecosystems such as the human gut. Current evidence suggests that the gut microbiota affect nutrient acquisition, energy harvest, and a myriad of host metabolic pathways.<br><br>CONCLUSION: Advances in the Human Microbiome Project and human metagenomics research will lead the way toward a greater understanding of the importance and role of the gut microbiome in metabolic disorders such as obesity, metabolic syndrome, and diabetes.}, }
@article {pmid23400224, year = {2013}, author = {Douglas-Escobar, M and Elliott, E and Neu, J}, title = {Effect of intestinal microbial ecology on the developing brain.}, journal = {JAMA pediatrics}, volume = {167}, number = {4}, pages = {374-379}, doi = {10.1001/jamapediatrics.2013.497}, pmid = {23400224}, issn = {2168-6211}, support = {R01 HD 059143/HD/NICHD NIH HHS/United States ; }, mesh = {Animals ; Brain/growth &amp; development/*physiology ; Child ; Child Development Disorders, Pervasive/epidemiology/microbiology ; Comorbidity ; Enteric Nervous System/physiology ; Gastrointestinal Diseases/epidemiology ; Humans ; Infant, Newborn ; Infant, Premature/physiology ; Intestines/immunology/*microbiology/*physiology ; Metagenome/immunology/*physiology ; Toll-Like Receptors/physiology ; }, abstract = {The mammalian gastrointestinal tract harbors a highly diverse microbial population that plays a major role in nutrition, metabolism, protection against pathogens, and development of the immune system. It is estimated that at least 1000 different bacterial species cohabit the human intestinal tract. Most recently, the Human Microbiome Project, using new genomic technologies, has started a catalog of specific microbiome composition and its correlation with health and specific diseases. Herein we provide a brief review of the intestinal microbiome, with a focus on new studies showing that there is an important link between the microbes that inhabit the intestinal tract and the developing brain. With future research, an understanding of this link may help us to treat various neurobehavioral problems such as autism, schizophrenia, and anxiety.}, }
@article {pmid23400030, year = {2013}, author = {Lau, S}, title = {What is new in the prevention of atopy and asthma?.}, journal = {Current opinion in allergy and clinical immunology}, volume = {13}, number = {2}, pages = {181-186}, doi = {10.1097/ACI.0b013e32835eb7b1}, pmid = {23400030}, issn = {1473-6322}, mesh = {Allergens/immunology ; Anti-Bacterial Agents/administration &amp; dosage ; Asthma/genetics/*prevention &amp; control ; Azithromycin/administration &amp; dosage ; Clinical Trials as Topic ; Feeding Behavior ; Genetic Predisposition to Disease ; Humans ; Hypersensitivity, Immediate/genetics/*prevention &amp; control ; *Immunomodulation ; Infant ; Metagenome/genetics ; Probiotics/administration &amp; dosage ; Vitamin D/administration &amp; dosage ; }, abstract = {PURPOSE OF REVIEW: Increasing understanding of mechanisms and influencing factors in the development of uncontrolled inflammatory responses in atopy and asthma should serve for the introduction of new preventive measures. This review tries to present the current state of the art and resumes that until now, no really effective concept can be offered to families at risk.<br><br>RECENT FINDINGS: In addition to modified feeding regimes (hydrolysed formula feeding in infancy), timing of the introduction of solids (avoidance of allergens versus early induction of tolerance), immune modulation using prebiotics or probiotics, a new target of potential intervention could be the human microbiome as a key player in the development of inflammatory diseases such as allergy and asthma. However, during the last 5 years, this concept could not yet be verified in interventional trials. There are new trials ongoing, studying the effect of microbial compounds in early infancy, vitamin D and polyunsaturated fatty acid supplementation during late pregnancy and the effect of azithromycin in children with recurrent wheeze. Results are to be expected within the next couple of years.<br><br>SUMMARY: New data on multifaceted intervention and the analysis of the human microbiome are to be expected. The recommendation for atopy and asthma prevention still focuses on avoidance of tobacco smoke exposure and food allergens during the first 4 months of life and feeding of hydrolysed formula if breast-feeding is not possible in high-risk infants, potentially early feeding of prebiotic sugars and/or certain strains of probiotic bacteria or bacterial compounds in certain subpopulations.}, }
@article {pmid23382060, year = {2013}, author = {Samaranayake, L}, title = {Human microbiome: a fascinating underworld dictating our health?.}, journal = {Journal of investigative and clinical dentistry}, volume = {4}, number = {1}, pages = {1-2}, doi = {10.1111/jicd.12037}, pmid = {23382060}, issn = {2041-1626}, mesh = {Ecology ; Humans ; Metagenome/immunology/*physiology ; Mouth/immunology/*microbiology ; }, }
@article {pmid23370376, year = {2013}, author = {Proal, AD and Albert, PJ and Marshall, TG}, title = {The human microbiome and autoimmunity.}, journal = {Current opinion in rheumatology}, volume = {25}, number = {2}, pages = {234-240}, doi = {10.1097/BOR.0b013e32835cedbf}, pmid = {23370376}, issn = {1531-6963}, mesh = {Adjuvants, Immunologic/therapeutic use ; Autoantibodies/biosynthesis ; Autoimmune Diseases/etiology/microbiology/therapy ; *Autoimmunity ; Family ; Female ; Host-Pathogen Interactions/immunology ; Humans ; Immunity, Innate ; Infections/immunology/microbiology ; Male ; Metagenome/*immunology ; Models, Immunological ; Molecular Mimicry/immunology ; Polymorphism, Single Nucleotide ; Receptors, Calcitriol/immunology ; }, abstract = {PURPOSE OF REVIEW: To demonstrate how dysbiosis of the human microbiome can drive autoimmune disease.<br><br>RECENT FINDINGS: Humans are superorganisms. The human body harbors an extensive microbiome, which has been shown to differ in patients with autoimmune diagnoses. Intracellular microbes slow innate immune defenses by dysregulating the vitamin D nuclear receptor, allowing pathogens to accumulate in tissue and blood. Molecular mimicry between pathogen and host causes further dysfunction by interfering with human protein interactions. Autoantibodies may well be created in response to pathogens.<br><br>SUMMARY: The catastrophic failure of human metabolism observed in autoimmune disease results from a common underlying pathogenesis - the successive accumulation of pathogens into the microbiome over time, and the ability of such pathogens to dysregulate gene transcription, translation, and human metabolic processes. Autoimmune diseases are more likely passed in families because of the inheritance of a familial microbiome, rather than Mendelian inheritance of genetic abnormalities. We can stimulate innate immune defenses and allow patients to target pathogens, but cell death results in immunopathology.}, }
@article {pmid23337890, year = {2013}, author = {Fitz-Gibbon, S and Tomida, S and Chiu, BH and Nguyen, L and Du, C and Liu, M and Elashoff, D and Erfe, MC and Loncaric, A and Kim, J and Modlin, RL and Miller, JF and Sodergren, E and Craft, N and Weinstock, GM and Li, H}, title = {Propionibacterium acnes strain populations in the human skin microbiome associated with acne.}, journal = {The Journal of investigative dermatology}, volume = {133}, number = {9}, pages = {2152-2160}, pmid = {23337890}, issn = {1523-1747}, support = {UH2AR057503/AR/NIAMS NIH HHS/United States ; UL1 TR000124/TR/NCATS NIH HHS/United States ; U54 HG004968/HG/NHGRI NIH HHS/United States ; U54HG004968/HG/NHGRI NIH HHS/United States ; UH2 AR057503/AR/NIAMS NIH HHS/United States ; }, mesh = {Acne Vulgaris/*microbiology ; Adult ; DNA, Bacterial/genetics ; Female ; Genomics/methods ; Gram-Positive Bacterial Infections/*microbiology ; Humans ; Male ; *Metagenome ; Propionibacterium acnes/*classification/*genetics/isolation &amp; purification ; RNA, Bacterial/genetics ; RNA, Ribosomal/genetics ; Ribotyping/methods ; Sebaceous Glands/microbiology ; Skin/microbiology ; Young Adult ; }, abstract = {The human skin microbiome has important roles in skin health and disease. However, bacterial population structure and diversity at the strain level is poorly understood. We compared the skin microbiome at the strain level and genome level of Propionibacterium acnes, a dominant skin commensal, between 49 acne patients and 52 healthy individuals by sampling the pilosebaceous units on their noses. Metagenomic analysis demonstrated that although the relative abundances of P. acnes were similar, the strain population structures were significantly different in the two cohorts. Certain strains were highly associated with acne, and other strains were enriched in healthy skin. By sequencing 66 previously unreported P. acnes strains and comparing 71 P. acnes genomes, we identified potential genetic determinants of various P. acnes strains in association with acne or health. Our analysis suggests that acquired DNA sequences and bacterial immune elements may have roles in determining virulence properties of P. acnes strains, and some could be future targets for therapeutic interventions. This study demonstrates a previously unreported paradigm of commensal strain populations that could explain the pathogenesis of human diseases. It underscores the importance of strain-level analysis of the human microbiome to define the role of commensals in health and disease.}, }
@article {pmid23327986, year = {2013}, author = {Amalaradjou, MA and Bhunia, AK}, title = {Bioengineered probiotics, a strategic approach to control enteric infections.}, journal = {Bioengineered}, volume = {4}, number = {6}, pages = {379-387}, pmid = {23327986}, issn = {2165-5987}, mesh = {Animals ; Anti-Infective Agents/administration &amp; dosage/*pharmacology ; Bioengineering ; Biotechnology ; Food Technology/*methods ; Foodborne Diseases/*prevention &amp; control ; Humans ; Models, Animal ; Probiotics/administration &amp; dosage/*pharmacology ; Stress, Physiological ; }, abstract = {Enteric infections account for high morbidity and mortality and are considered to be the fifth leading cause of death at all ages worldwide. Seventy percent of all enteric infections are foodborne. Thus significant efforts have been directed toward the detection, control and prevention of foodborne diseases. Many antimicrobials including antibiotics have been used for their control and prevention. However, probiotics offer a potential alternative intervention strategy owing to their general health beneficial properties and inhibitory effects against foodborne pathogens. Often, antimicrobial probiotic action is non-specific and non-discriminatory or may be ineffective. In such cases, bioengineered probiotics expressing foreign gene products to achieve specific function is highly desirable. In this review we summarize the strategic development of recombinant bioengineered probiotics to control enteric infections, and to examine how scientific advancements in the human microbiome and their immunomodulatory effects help develop such novel and safe bioengineered probiotics.}, }
@article {pmid23327521, year = {2013}, author = {Eloe-Fadrosh, EA and Rasko, DA}, title = {The human microbiome: from symbiosis to pathogenesis.}, journal = {Annual review of medicine}, volume = {64}, number = {}, pages = {145-163}, pmid = {23327521}, issn = {1545-326X}, support = {U01 AT002388/AT/NCCIH NIH HHS/United States ; RC4 AI092828/AI/NIAID NIH HHS/United States ; U19 AI082655/AI/NIAID NIH HHS/United States ; U01 AT002952/AT/NCCIH NIH HHS/United States ; RC4 AI092828A/AI/NIAID NIH HHS/United States ; }, mesh = {Environment ; Gastrointestinal Tract/*microbiology ; Humans ; Metagenome/*physiology ; Symbiosis/*physiology ; }, abstract = {The human microbiota is a complex assemblage of the microbes inhabiting many sites in the human body. Recent advances in technology have enabled deep sequencing and analysis of the members and structures of these communities. Two sites, the vagina and gastrointestinal tract, are highlighted to exemplify how technological advances have enhanced our knowledge of the host-microbiota system. These examples represent low- and high-complexity communities, respectively. In each example, certain community structures are identified that can be extrapolated to larger collections representing multiple individuals and potential disease or health states. One common feature is the unexpected diversity of the microbiota at any of these locations, which poses a challenge for relating the microbiota to health and disease. However, we anticipate microbiota compositional measurements could become standard clinical practice in the future and may become diagnostic for certain diseases or increased susceptibility to certain disorders. The microbiota of a number of disease states are currently being examined to identify potential correlations. In line with these predictions, it is possible that existing conditions may be resolved by altering the microbiota in a positive way.}, }
@article {pmid23326225, year = {2013}, author = {Koren, O and Knights, D and Gonzalez, A and Waldron, L and Segata, N and Knight, R and Huttenhower, C and Ley, RE}, title = {A guide to enterotypes across the human body: meta-analysis of microbial community structures in human microbiome datasets.}, journal = {PLoS computational biology}, volume = {9}, number = {1}, pages = {e1002863}, pmid = {23326225}, issn = {1553-7358}, support = {HG4872/HG/NHGRI NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; U01 HG004866/HG/NHGRI NIH HHS/United States ; R01 HG004872/HG/NHGRI NIH HHS/United States ; 1R01HG005969/HG/NHGRI NIH HHS/United States ; R01 HG005969/HG/NHGRI NIH HHS/United States ; }, mesh = {Bacteria/*classification/genetics ; Biodiversity ; Humans ; *Metagenome ; RNA, Ribosomal, 16S/genetics ; }, abstract = {Recent analyses of human-associated bacterial diversity have categorized individuals into 'enterotypes' or clusters based on the abundances of key bacterial genera in the gut microbiota. There is a lack of consensus, however, on the analytical basis for enterotypes and on the interpretation of these results. We tested how the following factors influenced the detection of enterotypes: clustering methodology, distance metrics, OTU-picking approaches, sequencing depth, data type (whole genome shotgun (WGS) vs.16S rRNA gene sequence data), and 16S rRNA region. We included 16S rRNA gene sequences from the Human Microbiome Project (HMP) and from 16 additional studies and WGS sequences from the HMP and MetaHIT. In most body sites, we observed smooth abundance gradients of key genera without discrete clustering of samples. Some body habitats displayed bimodal (e.g., gut) or multimodal (e.g., vagina) distributions of sample abundances, but not all clustering methods and workflows accurately highlight such clusters. Because identifying enterotypes in datasets depends not only on the structure of the data but is also sensitive to the methods applied to identifying clustering strength, we recommend that multiple approaches be used and compared when testing for enterotypes.}, }
@article {pmid23322636, year = {2013}, author = {Guinane, CM and Tadrous, A and Fouhy, F and Ryan, CA and Dempsey, EM and Murphy, B and Andrews, E and Cotter, PD and Stanton, C and Ross, RP}, title = {Microbial composition of human appendices from patients following appendectomy.}, journal = {mBio}, volume = {4}, number = {1}, pages = {}, pmid = {23322636}, issn = {2150-7511}, mesh = {Adolescent ; Adult ; Appendectomy ; Appendicitis/surgery ; Appendix/*microbiology ; Bacteria/*classification/*genetics ; *Biodiversity ; Child, Preschool ; DNA, Bacterial/chemistry/genetics ; DNA, Ribosomal/chemistry/genetics ; Female ; Humans ; Male ; *Metagenome ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; Young Adult ; }, abstract = {UNLABELLED: The human appendix has historically been considered a vestige of evolutionary development with an unknown function. While limited data are available on the microbial composition of the appendix, it has been postulated that this organ could serve as a microbial reservoir for repopulating the gastrointestinal tract in times of necessity. We aimed to explore the microbial composition of the human appendix, using high-throughput sequencing of the 16S rRNA gene V4 region. Seven patients, 5 to 25 years of age, presenting with symptoms of acute appendicitis were included in this study. Results showed considerable diversity and interindividual variability among the microbial composition of the appendix samples. In general, however, Firmicutes was the dominant phylum, with the majority of additional sequences being assigned at various levels to Proteobacteria, Bacteroidetes, Actinobacteria, and Fusobacteria. Despite the large diversity in the microbiota found within the appendix, however, a few major families and genera were found to comprise the majority of the sequences present. Interestingly, also, certain taxa not generally associated with the human intestine, including the oral pathogens Gemella, Parvimonas, and Fusobacterium, were identified among the appendix samples. The prevalence of genera such as Fusobacterium could also be linked to the severity of inflammation of the organ. We conclude that the human appendix contains a robust and varied microbiota distinct from the microbiotas in other niches within the human microbiome. The microbial composition of the human appendix is subject to extreme variability and comprises a diversity of biota that may play an important, as-yet-unknown role in human health.<br><br>IMPORTANCE: There are currently limited data available on the microbial composition of the human appendix. It has been suggested, however, that it may serve as a "safe house" for commensal bacteria that can reinoculate the gut at need. The present study is the first comprehensive view of the microbial composition of the appendix as determined by high-throughput sequencing. We have determined that the human appendix contains a wealth of microbes, including members of 15 phyla. Important information regarding the associated bacterial diversity of the appendix which will help determine the role, if any, the appendix microbiota has in human health is presented.}, }
@article {pmid23316946, year = {2013}, author = {Zhou, Y and Gao, H and Mihindukulasuriya, KA and La Rosa, PS and Wylie, KM and Vishnivetskaya, T and Podar, M and Warner, B and Tarr, PI and Nelson, DE and Fortenberry, JD and Holland, MJ and Burr, SE and Shannon, WD and Sodergren, E and Weinstock, GM}, title = {Biogeography of the ecosystems of the healthy human body.}, journal = {Genome biology}, volume = {14}, number = {1}, pages = {R1}, pmid = {23316946}, issn = {1474-760X}, support = {UH3 AI083265/AI/NIAID NIH HHS/United States ; U54 HG004968/HG/NHGRI NIH HHS/United States ; 5P30 DK052574/DK/NIDDK NIH HHS/United States ; U54HG004968/HG/NHGRI NIH HHS/United States ; UH3 AI094641/AI/NIAID NIH HHS/United States ; 1R01HG004857/HG/NHGRI NIH HHS/United States ; }, mesh = {Healthy Volunteers ; Humans ; *Microbiota ; Mouth/*microbiology ; Organ Specificity ; RNA, Ribosomal, 16S/genetics ; Skin/*microbiology ; Urogenital System/*microbiology ; }, abstract = {BACKGROUND: Characterizing the biogeography of the microbiome of healthy humans is essential for understanding microbial associated diseases. Previous studies mainly focused on a single body habitat from a limited set of subjects. Here, we analyzed one of the largest microbiome datasets to date and generated a biogeographical map that annotates the biodiversity, spatial relationships, and temporal stability of 22 habitats from 279 healthy humans.<br><br>RESULTS: We identified 929 genera from more than 24 million 16S rRNA gene sequences of 22 habitats, and we provide a baseline of inter-subject variation for healthy adults. The oral habitat has the most stable microbiota with the highest alpha diversity, while the skin and vaginal microbiota are less stable and show lower alpha diversity. The level of biodiversity in one habitat is independent of the biodiversity of other habitats in the same individual. The abundances of a given genus at a body site in which it dominates do not correlate with the abundances at body sites where it is not dominant. Additionally, we observed the human microbiota exhibit both cosmopolitan and endemic features. Finally, comparing datasets of different projects revealed a project-based clustering pattern, emphasizing the significance of standardization of metagenomic studies.<br><br>CONCLUSIONS: The data presented here extend the definition of the human microbiome by providing a more complete and accurate picture of human microbiome biogeography, addressing questions best answered by a large dataset of subjects and body sites that are deeply sampled by sequencing.}, }
@article {pmid23308060, year = {2013}, author = {Skunca, N and Bošnjak, M and Kriško, A and Panov, P and Džeroski, S and Smuc, T and Supek, F}, title = {Phyletic profiling with cliques of orthologs is enhanced by signatures of paralogy relationships.}, journal = {PLoS computational biology}, volume = {9}, number = {1}, pages = {e1002852}, pmid = {23308060}, issn = {1553-7358}, mesh = {Escherichia coli/genetics ; *Gene Expression Profiling ; Genes, Bacterial ; Models, Theoretical ; *Phylogeny ; }, abstract = {New microbial genomes are sequenced at a high pace, allowing insight into the genetics of not only cultured microbes, but a wide range of metagenomic collections such as the human microbiome. To understand the deluge of genomic data we face, computational approaches for gene functional annotation are invaluable. We introduce a novel model for computational annotation that refines two established concepts: annotation based on homology and annotation based on phyletic profiling. The phyletic profiling-based model that includes both inferred orthologs and paralogs-homologs separated by a speciation and a duplication event, respectively-provides more annotations at the same average Precision than the model that includes only inferred orthologs. For experimental validation, we selected 38 poorly annotated Escherichia coli genes for which the model assigned one of three GO terms with high confidence: involvement in DNA repair, protein translation, or cell wall synthesis. Results of antibiotic stress survival assays on E. coli knockout mutants showed high agreement with our model's estimates of accuracy: out of 38 predictions obtained at the reported Precision of 60%, we confirmed 25 predictions, indicating that our confidence estimates can be used to make informed decisions on experimental validation. Our work will contribute to making experimental validation of computational predictions more approachable, both in cost and time. Our predictions for 998 prokaryotic genomes include ~400000 specific annotations with the estimated Precision of 90%, ~19000 of which are highly specific-e.g. "penicillin binding," "tRNA aminoacylation for protein translation," or "pathogenesis"-and are freely available at http://gorbi.irb.hr/.}, }
@article {pmid23302789, year = {2013}, author = {Mayer, FL and Wilson, D and Hube, B}, title = {Candida albicans pathogenicity mechanisms.}, journal = {Virulence}, volume = {4}, number = {2}, pages = {119-128}, pmid = {23302789}, issn = {2150-5608}, mesh = {Candida albicans/*pathogenicity ; Candidiasis/*microbiology/*pathology ; Humans ; Virulence Factors/*metabolism ; }, abstract = {The polymorphic fungus Candida albicans is a member of the normal human microbiome. In most individuals, C. albicans resides as a lifelong, harmless commensal. Under certain circumstances, however, C. albicans can cause infections that range from superficial infections of the skin to life-threatening systemic infections. Several factors and activities have been identified which contribute to the pathogenic potential of this fungus. Among them are molecules which mediate adhesion to and invasion into host cells, the secretion of hydrolases, the yeast-to-hypha transition, contact sensing and thigmotropism, biofilm formation, phenotypic switching and a range of fitness attributes. Our understanding of when and how these mechanisms and factors contribute to infection has significantly increased during the last years. In addition, novel virulence mechanisms have recently been discovered. In this review we present an update on our current understanding of the pathogenicity mechanisms of this important human pathogen.}, }
@article {pmid23282177, year = {2012}, author = {Fettweis, JM and Serrano, MG and Sheth, NU and Mayer, CM and Glascock, AL and Brooks, JP and Jefferson, KK and ,  and Buck, GA}, title = {Species-level classification of the vaginal microbiome.}, journal = {BMC genomics}, volume = {13 Suppl 8}, number = {Suppl 8}, pages = {S17}, pmid = {23282177}, issn = {1471-2164}, support = {UH2/UH3AI083263/AI/NIAID NIH HHS/United States ; }, mesh = {Algorithms ; Bacteria/*classification/genetics ; Databases, Genetic ; Female ; Humans ; *Metagenome ; RNA, Ribosomal, 16S/genetics ; Vagina/*microbiology ; }, abstract = {BACKGROUND: The application of next-generation sequencing to the study of the vaginal microbiome is revealing the spectrum of microbial communities that inhabit the human vagina. High-resolution identification of bacterial taxa, minimally to the species level, is necessary to fully understand the association of the vaginal microbiome with bacterial vaginosis, sexually transmitted infections, pregnancy complications, menopause, and other physiological and infectious conditions. However, most current taxonomic assignment strategies based on metagenomic 16S rDNA sequence analysis provide at best a genus-level resolution. While surveys of 16S rRNA gene sequences are common in microbiome studies, few well-curated, body-site-specific reference databases of 16S rRNA gene sequences are available, and no such resource is available for vaginal microbiome studies.<br><br>RESULTS: We constructed the Vaginal 16S rDNA Reference Database, a comprehensive and non-redundant database of 16S rDNA reference sequences for bacterial taxa likely to be associated with vaginal health, and we developed STIRRUPS, a new method that employs the USEARCH algorithm with a curated reference database for rapid species-level classification of 16S rDNA partial sequences. The method was applied to two datasets of V1-V3 16S rDNA reads: one generated from a mock community containing DNA from six bacterial strains associated with vaginal health, and a second generated from over 1,000 mid-vaginal samples collected as part of the Vaginal Human Microbiome Project at Virginia Commonwealth University. In both datasets, STIRRUPS, used in conjunction with the Vaginal 16S rDNA Reference Database, classified more than 95% of processed reads to a species-level taxon using a 97% global identity threshold for assignment.<br><br>CONCLUSIONS: This database and method provide accurate species-level classifications of metagenomic 16S rDNA sequence reads that will be useful for analysis and comparison of microbiome profiles from vaginal samples. STIRRUPS can be used to classify 16S rDNA sequence reads from other ecological niches if an appropriate reference database of 16S rDNA sequences is available.}, }
@article {pmid23281612, year = {2012}, author = {Harwich, MD and Serrano, MG and Fettweis, JM and Alves, JM and Reimers, MA and ,  and Buck, GA and Jefferson, KK}, title = {Genomic sequence analysis and characterization of Sneathia amnii sp. nov.}, journal = {BMC genomics}, volume = {13 Suppl 8}, number = {Suppl 8}, pages = {S4}, pmid = {23281612}, issn = {1471-2164}, support = {2P30 CA16059/CA/NCI NIH HHS/United States ; 4UH3AI083263/AI/NIAID NIH HHS/United States ; 5P30NS047463/NS/NINDS NIH HHS/United States ; }, mesh = {Anti-Bacterial Agents/pharmacology ; Female ; *Genome, Bacterial ; Humans ; Leptotrichia/classification/drug effects/*genetics ; Metagenome ; Microbial Sensitivity Tests ; Phenotype ; Phylogeny ; RNA, Ribosomal, 16S/genetics ; *Sequence Analysis, DNA ; Vagina/microbiology ; Virulence/genetics ; }, abstract = {BACKGROUND: Bacteria of the genus Sneathia are emerging as potential pathogens of the female reproductive tract. Species of Sneathia, which were formerly grouped with Leptotrichia, can be part of the normal microbiota of the genitourinary tracts of men and women, but they are also associated with a variety of clinical conditions including bacterial vaginosis, preeclampsia, preterm labor, spontaneous abortion, post-partum bacteremia and other invasive infections. Sneathia species also exhibit a significant correlation with sexually transmitted diseases and cervical cancer. Because Sneathia species are fastidious and rarely cultured successfully in vitro; and the genomes of members of the genus had until now not been characterized, very little is known about the physiology or the virulence of these organisms.<br><br>RESULTS: Here, we describe a novel species, Sneathia amnii sp. nov, which closely resembles bacteria previously designated "Leptotrichia amnionii". As part of the Vaginal Human Microbiome Project at VCU, a vaginal isolate of S. amnii sp. nov. was identified, successfully cultured and bacteriologically cloned. The biochemical characteristics and virulence properties of the organism were examined in vitro, and the genome of the organism was sequenced, annotated and analyzed. The analysis revealed a reduced circular genome of ~1.34 Mbp, containing ~1,282 protein-coding genes. Metabolic reconstruction of the bacterium reflected its biochemical phenotype, and several genes potentially associated with pathogenicity were identified.<br><br>CONCLUSIONS: Bacteria with complex growth requirements frequently remain poorly characterized and, as a consequence, their roles in health and disease are unclear. Elucidation of the physiology and identification of genes putatively involved in the metabolism and virulence of S. amnii may lead to a better understanding of the role of this potential pathogen in bacterial vaginosis, preterm birth, and other issues associated with vaginal and reproductive health.}, }
@article {pmid23300406, year = {2012}, author = {Morgan, XC and Huttenhower, C}, title = {Chapter 12: Human microbiome analysis.}, journal = {PLoS computational biology}, volume = {8}, number = {12}, pages = {e1002808}, pmid = {23300406}, issn = {1553-7358}, support = {R01 HG005969/HG/NHGRI NIH HHS/United States ; 1R01HG005969-01/HG/NHGRI NIH HHS/United States ; }, mesh = {Bacteria/genetics/isolation &amp; purification ; Genes, Bacterial ; Host-Pathogen Interactions ; Humans ; *Metagenome ; Metagenomics ; RNA, Ribosomal, 16S/genetics ; }, abstract = {Humans are essentially sterile during gestation, but during and after birth, every body surface, including the skin, mouth, and gut, becomes host to an enormous variety of microbes, bacterial, archaeal, fungal, and viral. Under normal circumstances, these microbes help us to digest our food and to maintain our immune systems, but dysfunction of the human microbiota has been linked to conditions ranging from inflammatory bowel disease to antibiotic-resistant infections. Modern high-throughput sequencing and bioinformatic tools provide a powerful means of understanding the contribution of the human microbiome to health and its potential as a target for therapeutic interventions. This chapter will first discuss the historical origins of microbiome studies and methods for determining the ecological diversity of a microbial community. Next, it will introduce shotgun sequencing technologies such as metagenomics and metatranscriptomics, the computational challenges and methods associated with these data, and how they enable microbiome analysis. Finally, it will conclude with examples of the functional genomics of the human microbiome and its influences upon health and disease.}, }
@article {pmid23296358, year = {2013}, author = {Foxman, B and Rosenthal, M}, title = {Implications of the human microbiome project for epidemiology.}, journal = {American journal of epidemiology}, volume = {177}, number = {3}, pages = {197-201}, pmid = {23296358}, issn = {1476-6256}, support = {R01 DE014899/DE/NIDCR NIH HHS/United States ; T32 AI049816/AI/NIAID NIH HHS/United States ; }, mesh = {Bacteria/genetics/isolation &amp; purification ; Epidemiology/*organization &amp; administration ; Fungi/genetics/isolation &amp; purification ; Humans ; *Metagenome ; Microbial Consortia ; Polymerase Chain Reaction ; Risk Factors ; Time Factors ; Viruses/genetics/isolation &amp; purification ; }, abstract = {The structure and function of microorganisms that live in and on us, the human microbiota, are a tremendous resource. Microbiota may help to explain individual variability in health outcomes and be a source of new biomarkers for environmental exposures and of novel prognostic and diagnostic indicators. The increase in availability of low-cost, high-throughput techniques makes it relatively straightforward to include microbiota assessments in epidemiologic studies. With the recent joint publications of the findings of the Human Microbiome Consortium and related studies, the consequent surge of interest in microbiome research, and remarkable media attention, the time is ripe for epidemiologists to contribute their expertise to and translate results of microbiota research for population health.}, }
@article {pmid23284876, year = {2012}, author = {La Rosa, PS and Brooks, JP and Deych, E and Boone, EL and Edwards, DJ and Wang, Q and Sodergren, E and Weinstock, G and Shannon, WD}, title = {Hypothesis testing and power calculations for taxonomic-based human microbiome data.}, journal = {PloS one}, volume = {7}, number = {12}, pages = {e52078}, pmid = {23284876}, issn = {1932-6203}, support = {U54 HG004968/HG/NHGRI NIH HHS/United States ; UH2 AI083265/AI/NIAID NIH HHS/United States ; 1UH2AI083265/AI/NIAID NIH HHS/United States ; }, mesh = {Adolescent ; Adult ; Algorithms ; Bacteria/classification/genetics ; Biodiversity ; Computational Biology ; Female ; Gingiva/microbiology ; Humans ; Male ; *Metagenome ; *Models, Statistical ; Reproducibility of Results ; Young Adult ; }, abstract = {This paper presents new biostatistical methods for the analysis of microbiome data based on a fully parametric approach using all the data. The Dirichlet-multinomial distribution allows the analyst to calculate power and sample sizes for experimental design, perform tests of hypotheses (e.g., compare microbiomes across groups), and to estimate parameters describing microbiome properties. The use of a fully parametric model for these data has the benefit over alternative non-parametric approaches such as bootstrapping and permutation testing, in that this model is able to retain more information contained in the data. This paper details the statistical approaches for several tests of hypothesis and power/sample size calculations, and applies them for illustration to taxonomic abundance distribution and rank abundance distribution data using HMP Jumpstart data on 24 subjects for saliva, subgingival, and supragingival samples. Software for running these analyses is available.}, }
@article {pmid23284280, year = {2012}, author = {O'Dwyer, JP and Kembel, SW and Green, JL}, title = {Phylogenetic diversity theory sheds light on the structure of microbial communities.}, journal = {PLoS computational biology}, volume = {8}, number = {12}, pages = {e1002832}, pmid = {23284280}, issn = {1553-7358}, support = {P50 GM098911/GM/NIGMS NIH HHS/United States ; 1P50GM098911/GM/NIGMS NIH HHS/United States ; }, mesh = {Humans ; *Metagenome ; *Models, Theoretical ; *Phylogeny ; }, abstract = {Microbial communities are typically large, diverse, and complex, and identifying and understanding the processes driving their structure has implications ranging from ecosystem stability to human health and well-being. Phylogenetic data gives us a new insight into these processes, providing a more informative perspective on functional and trait diversity than taxonomic richness alone. But the sheer scale of high resolution phylogenetic data also presents a new challenge to ecological theory. We bring a sampling theory perspective to microbial communities, considering a local community of co-occuring organisms as a sample from a larger regional pool, and apply our framework to make analytical predictions for local phylogenetic diversity arising from a given metacommunity and community assembly process. We characterize community assembly in terms of quantitative descriptions of clustered, random and overdispersed sampling, which have been associated with hypotheses of environmental filtering and competition. Using our approach, we analyze large microbial communities from the human microbiome, uncovering significant variation in diversity across habitats relative to the null hypothesis of random sampling.}, }
@article {pmid24826073, year = {2013}, author = {Neelakanta, G and Sultana, H}, title = {The use of metagenomic approaches to analyze changes in microbial communities.}, journal = {Microbiology insights}, volume = {6}, number = {}, pages = {37-48}, pmid = {24826073}, issn = {1178-6361}, abstract = {Microbes are the most abundant biological entities found in the biosphere. Identification and measurement of microorganisms (including viruses, bacteria, archaea, fungi, and protists) in the biosphere cannot be readily achieved due to limitations in culturing methods. A non-culture based approach, called "metagenomics", was developed that enabled researchers to comprehensively analyse microbial communities in different ecosystems. In this study, we highlight recent advances in the field of metagenomics for analyzing microbial communities in different ecosystems ranging from oceans to the human microbiome. Developments in several bioinformatics approaches are also discussed in context of microbial metagenomics that include taxonomic systems, sequence databases, and sequence-alignment tools. In summary, we provide a snapshot for the recent advances in metagenomics approach for analyzing changes in the microbial communities in different ecosystems.}, }
@article {pmid23251439, year = {2012}, author = {Tito, RY and Knights, D and Metcalf, J and Obregon-Tito, AJ and Cleeland, L and Najar, F and Roe, B and Reinhard, K and Sobolik, K and Belknap, S and Foster, M and Spicer, P and Knight, R and Lewis, CM}, title = {Insights from characterizing extinct human gut microbiomes.}, journal = {PloS one}, volume = {7}, number = {12}, pages = {e51146}, pmid = {23251439}, issn = {1932-6203}, support = {R01 GM089886/GM/NIGMS NIH HHS/United States ; R01 HG005172/HG/NHGRI NIH HHS/United States ; R01 HG005172-01/HG/NHGRI NIH HHS/United States ; R01 GM089886-01A1/GM/NIGMS NIH HHS/United States ; }, mesh = {Africa ; *Archaeology ; Bayes Theorem ; Child ; Chile ; DNA, Ribosomal/genetics ; Humans ; Intestines/*microbiology ; *Metagenome ; Mexico ; RNA, Ribosomal, 16S/genetics ; United States ; }, abstract = {In an effort to better understand the ancestral state of the human distal gut microbiome, we examine feces retrieved from archaeological contexts (coprolites). To accomplish this, we pyrosequenced the 16S rDNA V3 region from duplicate coprolite samples recovered from three archaeological sites, each representing a different depositional environment: Hinds Cave (~8000 years B.P.) in the southern United States, Caserones (1600 years B.P.) in northern Chile, and Rio Zape in northern Mexico (1400 years B.P.). Clustering algorithms grouped samples from the same site. Phyletic representation was more similar within sites than between them. A Bayesian approach to source-tracking was used to compare the coprolite data to published data from known sources that include, soil, compost, human gut from rural African children, human gut, oral and skin from US cosmopolitan adults and non-human primate gut. The data from the Hinds Cave samples largely represented unknown sources. The Caserones samples, retrieved directly from natural mummies, matched compost in high proportion. A substantial and robust proportion of Rio Zape data was predicted to match the gut microbiome found in traditional rural communities, with more minor matches to other sources. One of the Rio Zape samples had taxonomic representation consistent with a child. To provide an idealized scenario for sample preservation, we also applied source tracking to previously published data for Ötzi the Iceman and a soldier frozen for 93 years on a glacier. Overall these studies reveal that human microbiome data has been preserved in some coprolites, and these preserved human microbiomes match more closely to those from the rural communities than to those from cosmopolitan communities. These results suggest that the modern cosmopolitan lifestyle resulted in a dramatic change to the human gut microbiome.}, }
@article {pmid23251414, year = {2012}, author = {Wang, K and Li, H and Yuan, Y and Etheridge, A and Zhou, Y and Huang, D and Wilmes, P and Galas, D}, title = {The complex exogenous RNA spectra in human plasma: an interface with human gut biota?.}, journal = {PloS one}, volume = {7}, number = {12}, pages = {e51009}, pmid = {23251414}, issn = {1932-6203}, mesh = {*Biota ; Gastrointestinal Tract ; Humans ; Metagenome ; Plasma/*metabolism ; RNA/*blood ; RNA, Circular ; }, abstract = {Human plasma has long been a rich source for biomarker discovery. It has recently become clear that plasma RNA molecules, such as microRNA, in addition to proteins are common and can serve as biomarkers. Surveying human plasma for microRNA biomarkers using next generation sequencing technology, we observed that a significant fraction of the circulating RNA appear to originate from exogenous species. With careful analysis of sequence error statistics and other controls, we demonstrated that there is a wide range of RNA from many different organisms, including bacteria and fungi as well as from other species. These RNAs may be associated with protein, lipid or other molecules protecting them from RNase activity in plasma. Some of these RNAs are detected in intracellular complexes and may be able to influence cellular activities under in vitro conditions. These findings raise the possibility that plasma RNAs of exogenous origin may serve as signaling molecules mediating for example the human-microbiome interaction and may affect and/or indicate the state of human health.}, }
@article {pmid23223587, year = {2013}, author = {Mitsuma, SF and Mansour, MK and Dekker, JP and Kim, J and Rahman, MZ and Tweed-Kent, A and Schuetz, P}, title = {Promising new assays and technologies for the diagnosis and management of infectious diseases.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {56}, number = {7}, pages = {996-1002}, pmid = {23223587}, issn = {1537-6591}, support = {T32 AI007061/AI/NIAID NIH HHS/United States ; T32-AI007061-35/AI/NIAID NIH HHS/United States ; }, mesh = {Clinical Laboratory Techniques/*methods/trends ; Communicable Diseases/*diagnosis ; Humans ; }, abstract = {In the first decade of the 21st century, we have seen the completion of the human genome project and marked progress in the human microbiome project. The vast amount of data generated from these efforts combined with advances in molecular and biomedical technologies have led to the development of a multitude of assays and technologies that may be useful in the diagnosis and management of infectious diseases. Here, we identify several new assays and technologies that have recently come into clinical use or have potential for clinical use in the near future. The scope of this review is broad and includes topics such as the serum marker procalcitonin, gene expression profiling, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS), and nucleic acid aptamers. Principles that underlie each assay or technology, their clinical applications, and potential strengths and limitations are addressed.}, }
@article {pmid23222524, year = {2013}, author = {Schloissnig, S and Arumugam, M and Sunagawa, S and Mitreva, M and Tap, J and Zhu, A and Waller, A and Mende, DR and Kultima, JR and Martin, J and Kota, K and Sunyaev, SR and Weinstock, GM and Bork, P}, title = {Genomic variation landscape of the human gut microbiome.}, journal = {Nature}, volume = {493}, number = {7430}, pages = {45-50}, pmid = {23222524}, issn = {1476-4687}, support = {U54 HG003079/HG/NHGRI NIH HHS/United States ; U54 HG004968/HG/NHGRI NIH HHS/United States ; U54HG003079/HG/NHGRI NIH HHS/United States ; U54HG004968/HG/NHGRI NIH HHS/United States ; }, mesh = {Europe ; Feces/microbiology ; Genetic Variation/*genetics ; Genome, Bacterial/genetics ; Genotype ; Geographic Mapping ; Humans ; Intestines/*microbiology ; Metagenome/*genetics ; North America ; Polymorphism, Single Nucleotide/genetics ; Reference Standards ; Time Factors ; }, abstract = {Whereas large-scale efforts have rapidly advanced the understanding and practical impact of human genomic variation, the practical impact of variation is largely unexplored in the human microbiome. We therefore developed a framework for metagenomic variation analysis and applied it to 252 faecal metagenomes of 207 individuals from Europe and North America. Using 7.4 billion reads aligned to 101 reference species, we detected 10.3 million single nucleotide polymorphisms (SNPs), 107,991 short insertions/deletions, and 1,051 structural variants. The average ratio of non-synonymous to synonymous polymorphism rates of 0.11 was more variable between gut microbial species than across human hosts. Subjects sampled at varying time intervals exhibited individuality and temporal stability of SNP variation patterns, despite considerable composition changes of their gut microbiota. This indicates that individual-specific strains are not easily replaced and that an individual might have a unique metagenomic genotype, which may be exploitable for personalized diet or drug intake.}, }
@article {pmid23218199, year = {2013}, author = {Lilley, EC and Silberg, JL}, title = {The Mid-Atlantic Twin Registry, revisited.}, journal = {Twin research and human genetics : the official journal of the International Society for Twin Studies}, volume = {16}, number = {1}, pages = {424-428}, doi = {10.1017/thg.2012.125}, pmid = {23218199}, issn = {1832-4274}, support = {UL1 TR000058/TR/NCATS NIH HHS/United States ; UL1TR000058/TR/NCATS NIH HHS/United States ; }, mesh = {Adolescent ; Adult ; Aged ; *Biomedical Research ; Child ; Child, Preschool ; Cohort Studies ; Diseases in Twins/*epidemiology/genetics/psychology ; Female ; Gene-Environment Interaction ; Humans ; Infant ; Infant, Newborn ; Male ; Middle Aged ; North Carolina/epidemiology ; *Registries ; South Carolina/epidemiology ; Twins, Dizygotic/*genetics ; Twins, Monozygotic/*genetics ; Virginia/epidemiology ; Young Adult ; }, abstract = {The Mid-Atlantic Twin Registry (MATR) is a population-based registry of more than 56,000 twins primarily born or living in Virginia, North Carolina, and South Carolina. The MATR employs several methods of ascertaining twins, and devotes considerable resources to tracking and maintaining communication with MATR participants. Researchers may utilize the MATR for administration of research services including study recruitment, collection of DNA, archival data set creation, as well as data collection through mailed, phone, or online surveys. In addition, the MATR houses the MATR Repository, with over 1,200 blood samples available for researchers interested in DNA genotyping. For over 35 years MATR twins have participated in research studies with investigators from diverse scientific disciplines and various institutions. These studies, which have resulted in numerous publications, have covered a range of topics, including the human microbiome, developmental psychopathology, depression, anxiety, substance use, epigenetics of aging, children of twins, pre-term birth, social attitudes, seizures, eating disorders, as well as sleep homeostasis. Researchers interested in utilizing twins are encouraged to contact the MATR to discuss potential research opportunities.}, }
@article {pmid23216677, year = {2012}, author = {Tyakht, AV and Popenko, AS and Belenikin, MS and Altukhov, IA and Pavlenko, AV and Kostryukova, ES and Selezneva, OV and Larin, AK and Karpova, IY and Alexeev, DG}, title = {MALINA: a web service for visual analytics of human gut microbiota whole-genome metagenomic reads.}, journal = {Source code for biology and medicine}, volume = {7}, number = {1}, pages = {13}, pmid = {23216677}, issn = {1751-0473}, abstract = {MALINA is a web service for bioinformatic analysis of whole-genome metagenomic data obtained from human gut microbiota sequencing. As input data, it accepts metagenomic reads of various sequencing technologies, including long reads (such as Sanger and 454 sequencing) and next-generation (including SOLiD and Illumina). It is the first metagenomic web service that is capable of processing SOLiD color-space reads, to authors' knowledge. The web service allows phylogenetic and functional profiling of metagenomic samples using coverage depth resulting from the alignment of the reads to the catalogue of reference sequences which are built into the pipeline and contain prevalent microbial genomes and genes of human gut microbiota. The obtained metagenomic composition vectors are processed by the statistical analysis and visualization module containing methods for clustering, dimension reduction and group comparison. Additionally, the MALINA database includes vectors of bacterial and functional composition for human gut microbiota samples from a large number of existing studies allowing their comparative analysis together with user samples, namely datasets from Russian Metagenome project, MetaHIT and Human Microbiome Project (downloaded from http://hmpdacc.org). MALINA is made freely available on the web at http://malina.metagenome.ru. The website is implemented in JavaScript (using Ext JS), Microsoft .NET Framework, MS SQL, Python, with all major browsers supported.}, }
@article {pmid23209389, year = {2012}, author = {Gevers, D and Pop, M and Schloss, PD and Huttenhower, C}, title = {Bioinformatics for the Human Microbiome Project.}, journal = {PLoS computational biology}, volume = {8}, number = {11}, pages = {e1002779}, pmid = {23209389}, issn = {1553-7358}, support = {U54HG004969/HG/NHGRI NIH HHS/United States ; P30 DK043351/DK/NIDDK NIH HHS/United States ; R01HG004885/HG/NHGRI NIH HHS/United States ; R01HG005975/HG/NHGRI NIH HHS/United States ; R01 HG005969/HG/NHGRI NIH HHS/United States ; U54 HG004969/HG/NHGRI NIH HHS/United States ; R01HG005969/HG/NHGRI NIH HHS/United States ; R01 HG005975/HG/NHGRI NIH HHS/United States ; R01 HG004885/HG/NHGRI NIH HHS/United States ; }, mesh = {*Computational Biology ; Database Management Systems ; Databases, Factual ; Humans ; *Metagenome ; Metagenomics ; }, }
@article {pmid23207600, year = {2013}, author = {Cario, E}, title = {Microbiota and innate immunity in intestinal inflammation and neoplasia.}, journal = {Current opinion in gastroenterology}, volume = {29}, number = {1}, pages = {85-91}, doi = {10.1097/MOG.0b013e32835a670e}, pmid = {23207600}, issn = {1531-7056}, mesh = {Enterocolitis/*immunology/microbiology ; Humans ; *Immunity, Innate ; Intestinal Neoplasms/*immunology/microbiology ; Metagenome/*immunology ; *Microbial Interactions ; Signal Transduction ; }, abstract = {PURPOSE OF REVIEW: This review focuses on recent advances and novel insights into the mechanistic events that may link commensal microbiota and host innate immunity in the pathophysiology of intestinal inflammation and neoplasia. Unanswered questions are discussed and future perspectives in the field are highlighted.<br><br>RECENT FINDINGS: Commensal microbiota, host innate immunity, and genetics form a multidimensional network that controls homeostasis of the mucosal barrier in the intestine. Large-scale sequencing projects have begun to catalog the healthy human microbiome. Converging evidence suggests that alterations in the regulation of the complex host environment [e.g., dysbiosis and overgrowth of select commensal bacterial species, dietary factors, copresence of facultative pathogens (including viruses), and changes in mucus characteristics] may trigger aberrant innate immune signaling, thereby contributing to the development of intestinal inflammation and associated colon cancer in the susceptible individual. Genetically determined innate immune malfunction may create an inflammatory environment that promotes tumor progression (such as the TLR4-D299G mutation).<br><br>SUMMARY: The next challenging steps to be taken are to decipher changes in the human microbiome (and virome) during well defined diseased states, and relate them to intestinal mucosal immune functions and host genotypes.}, }
@article {pmid23196853, year = {2013}, author = {Buccigrossi, V and Nicastro, E and Guarino, A}, title = {Functions of intestinal microflora in children.}, journal = {Current opinion in gastroenterology}, volume = {29}, number = {1}, pages = {31-38}, doi = {10.1097/MOG.0b013e32835a3500}, pmid = {23196853}, issn = {1531-7056}, mesh = {Child ; Enterocolitis, Necrotizing/microbiology/therapy ; Humans ; Inflammatory Bowel Diseases/microbiology ; Intestinal Diseases/*microbiology/therapy ; Intestines/*microbiology ; Irritable Bowel Syndrome/microbiology/therapy ; Metagenome/*physiology ; Probiotics/therapeutic use ; }, abstract = {PURPOSE OF REVIEW: This review discusses the structural composition of intestinal microbiota, the functional relationship between the latter and the host, and the role of abnormal microflora in chronic diseases.<br><br>RECENT FINDINGS: A more complete view of the gut microbiota is being developed following the Human Microbiome Project. The microflora in children is plastic, susceptible to changes in response to diet modifications, antibiotic treatment and other events, providing the opportunity to study its functional role. Increasing evidence highlights the role of nutrition in the age-related development of microflora. Eubiosis, that is, a normal microflora structure, provides protection against infections, educates the immune system, ensures tolerance to foods, and contributes to nutrient digestion and energy harvest. Changes in microflora, consisting in the overpresence of harmful species or underpresence of commensal species, or dysbiosis produce dysfunctions, such as intestinal inflammation or dysmotility. Moreover abnormal pattern of microflora have been consistently detected in specific diseases.<br><br>SUMMARY: A relationship exists between eubiosis and functions and conversely between dysbiosis and dysfunctions or even diseases. Abnormalities in microflora composition may trigger or contribute to specific diseases. This raises the hypothesis to target microflora in order to restore eubiosis through the use of antibiotics, probiotics or nutrients.}, }
@article {pmid23194438, year = {2012}, author = {Saad, R and Rizkallah, MR and Aziz, RK}, title = {Gut Pharmacomicrobiomics: the tip of an iceberg of complex interactions between drugs and gut-associated microbes.}, journal = {Gut pathogens}, volume = {4}, number = {1}, pages = {16}, pmid = {23194438}, issn = {1757-4749}, abstract = {The influence of resident gut microbes on xenobiotic metabolism has been investigated at different levels throughout the past five decades. However, with the advance in sequencing and pyrotagging technologies, addressing the influence of microbes on xenobiotics had to evolve from assessing direct metabolic effects on toxins and botanicals by conventional culture-based techniques to elucidating the role of community composition on drugs metabolic profiles through DNA sequence-based phylogeny and metagenomics. Following the completion of the Human Genome Project, the rapid, substantial growth of the Human Microbiome Project (HMP) opens new horizons for studying how microbiome compositional and functional variations affect drug action, fate, and toxicity (pharmacomicrobiomics), notably in the human gut. The HMP continues to characterize the microbial communities associated with the human gut, determine whether there is a common gut microbiome profile shared among healthy humans, and investigate the effect of its alterations on health. Here, we offer a glimpse into the known effects of the gut microbiota on xenobiotic metabolism, with emphasis on cases where microbiome variations lead to different therapeutic outcomes. We discuss a few examples representing how the microbiome interacts with human metabolic enzymes in the liver and intestine. In addition, we attempt to envisage a roadmap for the future implications of the HMP on therapeutics and personalized medicine.}, }
@article {pmid23178636, year = {2013}, author = {Xia, LC and Ai, D and Cram, J and Fuhrman, JA and Sun, F}, title = {Efficient statistical significance approximation for local similarity analysis of high-throughput time series data.}, journal = {Bioinformatics (Oxford, England)}, volume = {29}, number = {2}, pages = {230-237}, pmid = {23178636}, issn = {1367-4811}, support = {R01 HG006137/HG/NHGRI NIH HHS/United States ; }, mesh = {Female ; Gene Expression Profiling ; High-Throughput Nucleotide Sequencing ; Humans ; Male ; Markov Chains ; Metagenome ; *Models, Statistical ; Software ; }, abstract = {MOTIVATION: Local similarity analysis of biological time series data helps elucidate the varying dynamics of biological systems. However, its applications to large scale high-throughput data are limited by slow permutation procedures for statistical significance evaluation.<br><br>RESULTS: We developed a theoretical approach to approximate the statistical significance of local similarity analysis based on the approximate tail distribution of the maximum partial sum of independent identically distributed (i.i.d.) random variables. Simulations show that the derived formula approximates the tail distribution reasonably well (starting at time points > 10 with no delay and > 20 with delay) and provides P-values comparable with those from permutations. The new approach enables efficient calculation of statistical significance for pairwise local similarity analysis, making possible all-to-all local association studies otherwise prohibitive. As a demonstration, local similarity analysis of human microbiome time series shows that core operational taxonomic units (OTUs) are highly synergetic and some of the associations are body-site specific across samples.<br><br>AVAILABILITY: The new approach is implemented in our eLSA package, which now provides pipelines for faster local similarity analysis of time series data. The tool is freely available from eLSA's website: http://meta.usc.edu/softs/lsa.<br><br>SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.<br><br>CONTACT: fsun@usc.edu.}, }
@article {pmid23170142, year = {2012}, author = {Moschen, AR and Wieser, V and Tilg, H}, title = {Dietary Factors: Major Regulators of the Gut's Microbiota.}, journal = {Gut and liver}, volume = {6}, number = {4}, pages = {411-416}, pmid = {23170142}, issn = {2005-1212}, abstract = {Dietary factors and the associated lifestyle play a major role in the pathophysiology of many diseases. Several diets, especially a Western lifestyle with a high consumption of meat and carbohydrates and a low consumption of vegetables, have been linked to common diseases, such as metabolic syndrome, atherosclerosis, inflammatory bowel diseases, and colon cancer. The gastrointestinal tract harbors a complex and yet mainly molecularly defined microbiota, which contains an enormous number of different species. Recent advances in sequencing technologies have allowed the characterization of the human microbiome and opened the possibility to study the effect of "environmental" factors on this microbiome. The most important environmental factor is probably "what we eat," and the initial studies have revealed fascinating results on the interaction of nutrients with our microbiota. Whereas short-term changes in dietary patterns may not have major influences, long-term diets can affect the microbiota in a substantial manner. This issue may potentially have major relevance for human gastrointestinal health and disease because our microbiota has features to regulate many immune and metabolic functions. Increasing our knowledge on the interaction between nutrients and microbiota may have tremendous consequences and result in a better understanding of diseases, even beyond the gastrointestinal tract, and finally lead to better preventive and therapeutic strategies.}, }
@article {pmid23165986, year = {2013}, author = {Aagaard, K and Petrosino, J and Keitel, W and Watson, M and Katancik, J and Garcia, N and Patel, S and Cutting, M and Madden, T and Hamilton, H and Harris, E and Gevers, D and Simone, G and McInnes, P and Versalovic, J}, title = {The Human Microbiome Project strategy for comprehensive sampling of the human microbiome and why it matters.}, journal = {FASEB journal : official publication of the Federation of American Societies for Experimental Biology}, volume = {27}, number = {3}, pages = {1012-1022}, pmid = {23165986}, issn = {1530-6860}, support = {U54 HG004973/HG/NHGRI NIH HHS/United States ; P30 DK043351/DK/NIDDK NIH HHS/United States ; U54 HG004968/HG/NHGRI NIH HHS/United States ; U54HG004973/HG/NHGRI NIH HHS/United States ; K23 HD070979/HD/NICHD NIH HHS/United States ; U54HG004968/HG/NHGRI NIH HHS/United States ; }, mesh = {Adolescent ; Adult ; Body Mass Index ; Female ; Gastrointestinal Tract/*microbiology ; Humans ; Male ; *Metagenome ; Mouth/*microbiology ; Skin/*microbiology ; Specimen Handling/*methods ; Vagina/*microbiology ; }, abstract = {The Human Microbiome Project used rigorous good clinical practice standards to complete comprehensive body site sampling in healthy 18- to 40-yr-old adults, creating an unparalleled reference set of microbiome specimens. To ensure that specimens represented minimally perturbed microbiomes, we first screened potential participants using exclusion criteria based on health history, including the presence of systemic diseases (e.g., hypertension, cancer, or immunodeficiency or autoimmune disorders), use of potential immunomodulators, and recent use of antibiotics or probiotics. Subsequent physical examinations excluded individuals based on body mass index (BMI), cutaneous lesions, and oral health. We screened 554 individuals to enroll 300 (149 men and 151 women, mean age 26 yr, mean BMI 24 kg/m, 20.0% racial minority, and 10.7% Hispanic). We obtained specimens from the oral cavity, nares, skin, gastrointestinal tract, and vagina (15 specimens from men and 18 from women). The study evaluated longitudinal changes in an individual's microbiome by sampling 279 participants twice (mean 212 d after the first sampling; range 30-359 d) and 100 individuals 3 times (mean 72 d after the second sampling; range 30-224 d). This sampling strategy yielded 11,174 primary specimens, from which 12,479 DNA samples were submitted to 4 centers for metagenomic sequencing. Our clinical design and well-defined reference cohort has laid a foundation for microbiome research.}, }
@article {pmid23152838, year = {2012}, author = {La Rosa, PS and Shands, B and Deych, E and Zhou, Y and Sodergren, E and Weinstock, G and Shannon, WD}, title = {Statistical object data analysis of taxonomic trees from human microbiome data.}, journal = {PloS one}, volume = {7}, number = {11}, pages = {e48996}, pmid = {23152838}, issn = {1932-6203}, support = {U54 HG004968/HG/NHGRI NIH HHS/United States ; UH2 AI083265/AI/NIAID NIH HHS/United States ; 1UH2AI083265/AI/NIAID NIH HHS/United States ; }, mesh = {Algorithms ; Bacteria/*classification/*genetics ; Host-Pathogen Interactions ; Humans ; *Metagenome ; *Metagenomics ; *Models, Statistical ; RNA, Ribosomal, 16S ; }, abstract = {Human microbiome research characterizes the microbial content of samples from human habitats to learn how interactions between bacteria and their host might impact human health. In this work a novel parametric statistical inference method based on object-oriented data analysis (OODA) for analyzing HMP data is proposed. OODA is an emerging area of statistical inference where the goal is to apply statistical methods to objects such as functions, images, and graphs or trees. The data objects that pertain to this work are taxonomic trees of bacteria built from analysis of 16S rRNA gene sequences (e.g. using RDP); there is one such object for each biological sample analyzed. Our goal is to model and formally compare a set of trees. The contribution of our work is threefold: first, a weighted tree structure to analyze RDP data is introduced; second, using a probability measure to model a set of taxonomic trees, we introduce an approximate MLE procedure for estimating model parameters and we derive LRT statistics for comparing the distributions of two metagenomic populations; and third the Jumpstart HMP data is analyzed using the proposed model providing novel insights and future directions of analysis.}, }
@article {pmid23148445, year = {2012}, author = {Greub, G}, title = {Culturomics: a new approach to study the human microbiome.}, journal = {Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases}, volume = {18}, number = {12}, pages = {1157-1159}, doi = {10.1111/1469-0691.12032}, pmid = {23148445}, issn = {1469-0691}, mesh = {Humans ; *Metagenome ; Metagenomics/*methods ; Microbiological Techniques/*methods ; Microbiology/trends ; }, }
@article {pmid23141757, year = {2013}, author = {Peyyala, R and Ebersole, JL}, title = {Multispecies biofilms and host responses: "discriminating the trees from the forest".}, journal = {Cytokine}, volume = {61}, number = {1}, pages = {15-25}, pmid = {23141757}, issn = {1096-0023}, support = {P20 GM103538/GM/NIGMS NIH HHS/United States ; R21 DE018177/DE/NIDCR NIH HHS/United States ; DE 018177/DE/NIDCR NIH HHS/United States ; }, mesh = {Biodiversity ; *Biofilms ; Host-Pathogen Interactions/*immunology/physiology ; Humans ; Metagenome/immunology ; Mouth/*microbiology/*pathology ; Periodontal Diseases/*microbiology ; }, abstract = {Periodontal diseases reflect a tissue destructive process of the hard and soft tissues of the periodontium that are initiated by the accumulation of multispecies bacterial biofilms in the subgingival sulcus. This accumulation, in both quantity and quality of bacteria, results in a chronic immunoinflammatory response of the host to control this noxious challenge, leading to collateral damage of the tissues. As knowledge of the characteristics of the host-bacterial interactions in the oral cavity has expanded, new knowledge has become available on the complexity of the microbial challenge and the repertoire of host responses to this challenge. Recent results from the Human Microbiome Project continue to extend the array of taxa, genera, and species of bacteria that inhabit the multiple niches in the oral cavity; however, there is rather sparse information regarding variations in how host cells discriminate commensal from pathogenic species, as well as how the host response is affected by the three-dimensional architecture and interbacterial interactions that occur in the oral biofilms. This review provides some insights into these processes by including existing literature on the biology of nonoral bacterial biofilms, and the more recent literature just beginning to document how the oral cavity responds to multispecies biofilms.}, }
@article {pmid23140990, year = {2013}, author = {Morgan, XC and Segata, N and Huttenhower, C}, title = {Biodiversity and functional genomics in the human microbiome.}, journal = {Trends in genetics : TIG}, volume = {29}, number = {1}, pages = {51-58}, pmid = {23140990}, issn = {0168-9525}, support = {R01 HG005969/HG/NHGRI NIH HHS/United States ; 1R01HG005969-01/HG/NHGRI NIH HHS/United States ; }, mesh = {*Biodiversity ; Computational Biology ; Gastrointestinal Tract/metabolism/*microbiology ; Genomics/*methods ; High-Throughput Nucleotide Sequencing ; Humans ; Microbiota/*genetics/physiology ; Phylogeny ; }, abstract = {Over the course of our lives, humans are colonized by a tremendous diversity of commensal microbes, which comprise the human microbiome. The collective genetic potential (metagenome) of the human microbiome is orders of magnitude more than the human genome, and it profoundly affects human health and disease in ways we are only beginning to understand. Advances in computing and high-throughput sequencing have enabled population-level surveys such as MetaHIT and the recently released Human Microbiome Project, detailed investigations of the microbiome in human disease, and mechanistic studies employing gnotobiotic model organisms. The resulting knowledge of human microbiome composition, function, and range of variation across multiple body sites has begun to assemble a rich picture of commensal host-microbe and microbe-microbe interactions as well as their roles in human health and disease and their potential as diagnostic and therapeutic tools.}, }
@article {pmid23136846, year = {2012}, author = {Liu, CM and Kachur, S and Dwan, MG and Abraham, AG and Aziz, M and Hsueh, PR and Huang, YT and Busch, JD and Lamit, LJ and Gehring, CA and Keim, P and Price, LB}, title = {FungiQuant: a broad-coverage fungal quantitative real-time PCR assay.}, journal = {BMC microbiology}, volume = {12}, number = {}, pages = {255}, pmid = {23136846}, issn = {1471-2180}, support = {R15 DE021194/DE/NIDCR NIH HHS/United States ; R15DE021194-01/DE/NIDCR NIH HHS/United States ; R01AI087409-01A1/AI/NIAID NIH HHS/United States ; }, mesh = {Colony Count, Microbial/*methods ; Fungi/isolation &amp; purification ; Genes, rRNA ; Humans ; Metagenome ; RNA, Fungal/genetics ; RNA, Ribosomal, 18S/genetics ; Real-Time Polymerase Chain Reaction/*methods ; Reproducibility of Results ; Sensitivity and Specificity ; }, abstract = {BACKGROUND: Fungal load quantification is a critical component of fungal community analyses. Limitation of current approaches for quantifying the fungal component in the human microbiome suggests the need for new broad-coverage techniques.<br><br>METHODS: We analyzed 2,085 18S rRNA gene sequences from the SILVA database for assay design. We generated and quantified plasmid standards using a qPCR-based approach. We evaluated assay coverage against 4,968 sequences and performed assay validation following the Minimum Information for Publication of Quantitative Real-Time PCR Experiments (MIQE) guidelines.<br><br>RESULTS: We designed FungiQuant, a TaqMan&#xae; qPCR assay targeting a 351 bp region in the fungal 18S rRNA gene. Our in silico analysis showed that FungiQuant is a perfect sequence match to 90.0% of the 2,617 fungal species analyzed. We showed that FungiQuant's is 100% sensitive and its amplification efficiencies ranged from 76.3% to 114.5%, with r(2)-values of >0.99 against the 69 fungal species tested. Additionally, FungiQuant inter- and intra-run coefficients of variance ranged from <10% and <20%, respectively. We further showed that FungiQuant has a limit of quantification 25 copies and a limit of detection at 5 copies. Lastly, by comparing results from human-only background DNA with low-level fungal DNA, we showed that amplification in two or three of a FungiQuant performed in triplicate is statistically significant for true positive fungal detection.<br><br>CONCLUSIONS: FungiQuant has comprehensive coverage against diverse fungi and is a robust quantification and detection tool for delineating between true fungal detection and non-target human DNA.}, }
@article {pmid23131830, year = {2012}, author = {Rogers, GB and Bruce, KD}, title = {Exploring the parallel development of microbial systems in neonates with cystic fibrosis.}, journal = {mBio}, volume = {3}, number = {6}, pages = {e00408-12}, pmid = {23131830}, issn = {2150-7511}, mesh = {*Biota ; Cystic Fibrosis/*microbiology ; Gastrointestinal Tract/*microbiology ; Humans ; *Metagenome ; Respiratory System/*microbiology ; }, abstract = {Recent studies have greatly extended our understanding of the microbiota present in and on the human body. Here, advanced sequencing strategies have provided unprecedented analytical power. The important implications that the emerging data have for human health emphasize the need to intensify research in this area (D. A. Relman, Nature 486:194-195, 2012). It is already clear from these studies that the microbiotas characterized in different body locations of healthy individuals are both complex and diverse (The Human Microbiome Project Consortium, Nature 486:215-221). These studies also provide a point of contrast for investigations that aim to characterize the microbiota present in disease conditions. In this regard, Madan et al. (mBio 3(4):e00251-12, 2012) monitored the development over time of microbiota in the oropharynges and feces of neonates with cystic fibrosis and explored the potential for interactions between these complex microbial systems.}, }
@article {pmid23117819, year = {2012}, author = {Fox, EP and Nobile, CJ}, title = {A sticky situation: untangling the transcriptional network controlling biofilm development in Candida albicans.}, journal = {Transcription}, volume = {3}, number = {6}, pages = {315-322}, pmid = {23117819}, issn = {2154-1272}, support = {T32 AI060537/AI/NIAID NIH HHS/United States ; K99AI100896/AI/NIAID NIH HHS/United States ; T32AI060537/AI/NIAID NIH HHS/United States ; R01 AI083311/AI/NIAID NIH HHS/United States ; R01AI083311/AI/NIAID NIH HHS/United States ; K99 AI100896/AI/NIAID NIH HHS/United States ; }, mesh = {Biofilms/*growth &amp; development ; Candida albicans/*physiology ; Gene Expression Regulation, Fungal ; Gene Regulatory Networks ; Transcription Factors/genetics ; *Transcription, Genetic ; }, abstract = {Candida albicans is a commensal microorganism of the human microbiome; it is also the most prevalent fungal pathogen of humans. Many infections caused by C. albicans are a direct consequence of its proclivity to form biofilms--resilient, surface-associated communities of cells where individual cells acquire specialized properties that are distinct from those observed in suspension cultures. We recently identified the transcriptional network that orchestrates the formation of biofilms in C. albicans. These results set the stage for understanding how biofilms are formed and, once formed, how the specialized properties of biofilms are elaborated. This information will provide new insight for understanding biofilms in more detail and may lead to improvements in preventing and treating biofilm-based infections in the future.}, }
@article {pmid23110633, year = {2012}, author = {Slashinski, MJ and McCurdy, SA and Achenbaum, LS and Whitney, SN and McGuire, AL}, title = {"Snake-oil," "quack medicine," and "industrially cultured organisms:" biovalue and the commercialization of human microbiome research.}, journal = {BMC medical ethics}, volume = {13}, number = {}, pages = {28}, pmid = {23110633}, issn = {1472-6939}, support = {R01HG004853/HG/NHGRI NIH HHS/United States ; }, mesh = {Awareness ; *Commerce ; Dietary Supplements ; Drug Industry/*ethics ; Ethics, Research ; Humans ; *Metagenome ; *Probiotics ; Public Health ; Public Opinion ; Quackery/*ethics ; *Research ; *Technology Transfer ; }, abstract = {BACKGROUND: Continued advances in human microbiome research and technologies raise a number of ethical, legal, and social challenges. These challenges are associated not only with the conduct of the research, but also with broader implications, such as the production and distribution of commercial products promising maintenance or restoration of good physical health and disease prevention. In this article, we document several ethical, legal, and social challenges associated with the commercialization of human microbiome research, focusing particularly on how this research is mobilized within economic markets for new public health uses.<br><br>METHODS: We conducted in-depth, semi-structured interviews (2009-2010) with 63 scientists, researchers, and National Institutes of Health project leaders ("investigators") involved with human microbiome research. Interviews explored a range of ethical, legal, and social dimensions of human microbiome research, including investigators' perspectives on commercialization. Using thematic content analysis, we identified and analyzed emergent themes and patterns.<br><br>RESULTS: Investigators discussed the commercialization of human microbiome research in terms of (1) commercialization, probiotics, and issues of safety, (2) public awareness of the benefits and risks of dietary supplements, and (3) regulation.<br><br>CONCLUSION: The prevailing theme of ethical, legal, social concern focused on the need to find a balance between the marketplace, scientific research, and the public's health. The themes we identified are intended to serve as points for discussions about the relationship between scientific research and the manufacture and distribution of over-the-counter dietary supplements in the United States.}, }
@article {pmid23071716, year = {2012}, author = {Conlan, S and Kong, HH and Segre, JA}, title = {Species-level analysis of DNA sequence data from the NIH Human Microbiome Project.}, journal = {PloS one}, volume = {7}, number = {10}, pages = {e47075}, pmid = {23071716}, issn = {1932-6203}, support = {UH3-AR057504/AR/NIAMS NIH HHS/United States ; //Intramural NIH HHS/United States ; }, mesh = {Databases, Nucleic Acid ; Drug Resistance, Bacterial ; Enterococcus faecalis/classification/*genetics ; Female ; Gastrointestinal Tract/microbiology ; Humans ; Klebsiella pneumoniae/classification/*genetics ; *Metagenome ; Mouth/microbiology ; National Institutes of Health (U.S.) ; Phylogeny ; *RNA, Ribosomal, 16S ; Sequence Analysis, DNA ; Skin/microbiology ; Staphylococcus aureus/classification/*genetics ; United States ; Vagina/microbiology ; }, abstract = {BACKGROUND: Outbreaks of antibiotic-resistant bacterial infections emphasize the importance of surveillance of potentially pathogenic bacteria. Genomic sequencing of clinical microbiological specimens expands our capacity to study cultivable, fastidious and uncultivable members of the bacterial community. Herein, we compared the primary data collected by the NIH's Human Microbiome Project (HMP) with published epidemiological surveillance data of Staphylococcus aureus.<br><br>METHODS: The HMP's initial dataset contained microbial survey data from five body regions (skin, nares, oral cavity, gut and vagina) of 242 healthy volunteers. A significant component of the HMP dataset was deep sequencing of the 16S ribosomal RNA gene, which contains variable regions enabling taxonomic classification. Since species-level identification is essential in clinical microbiology, we built a reference database and used phylogenetic placement followed by most recent common ancestor classification to look at the species distribution for Staphylococcus, Klebsiella and Enterococcus.<br><br>MAIN RESULTS: We show that selecting the accurate region of the 16S rRNA gene to sequence is analogous to carefully selecting culture conditions to distinguish closely related bacterial species. Analysis of the HMP data showed that Staphylococcus aureus was present in the nares of 36% of healthy volunteers, consistent with culture-based epidemiological data. Klebsiella pneumoniae and Enterococcus faecalis were found less frequently, but across many habitats.<br><br>CONCLUSIONS: This work demonstrates that large 16S rRNA survey studies can be used to support epidemiological goals in the context of an increasing awareness that microbes flourish and compete within a larger bacterial community. This study demonstrates how genomic techniques and information could be critically important to trace microbial evolution and implement hospital infection control.}, }
@article {pmid23054706, year = {2012}, author = {Kim, S and Kim, YM and Kwak, YS}, title = {A novel therapeutic target, GPR43; where it stands in drug discovery.}, journal = {Archives of pharmacal research}, volume = {35}, number = {9}, pages = {1505-1509}, doi = {10.1007/s12272-012-0900-6}, pmid = {23054706}, issn = {1976-3786}, mesh = {Adipogenesis/*drug effects ; Animals ; Anti-Inflammatory Agents, Non-Steroidal/pharmacology/therapeutic use ; Drug Discovery ; Drugs, Investigational/*pharmacology/therapeutic use ; Humans ; Ligands ; Lipolysis/*drug effects ; Metabolic Syndrome/drug therapy/metabolism ; Molecular Targeted Therapy ; Overweight/drug therapy/immunology/metabolism ; Receptors, Cell Surface/*agonists/*antagonists &amp; inhibitors/genetics/metabolism ; }, abstract = {With growing interest in human microbiome for its implication in metabolic disorders, inflammatory diseases, immune disorders and so forth, understanding the biology at the interface of the gut flora and the host becomes very important for identifying novel therapeutic avenues. GPR43 has been deorphanized and the metabolites of microbiome, such as short-chain fatty acids, serve as its natural ligands. There are numerous reports that GPR43 might be a crucial link to the novel therapies for the unmet medical needs and many drug discovery organizations are making their moves in response.}, }
@article {pmid23033473, year = {2012}, author = {Jorth, P and Whiteley, M}, title = {An evolutionary link between natural transformation and CRISPR adaptive immunity.}, journal = {mBio}, volume = {3}, number = {5}, pages = {}, pmid = {23033473}, issn = {2150-7511}, support = {F31 DE021633/DE/NIDCR NIH HHS/United States ; R01 DE020100/DE/NIDCR NIH HHS/United States ; 5F31DE021633-02/DE/NIDCR NIH HHS/United States ; 1R01DE020100/DE/NIDCR NIH HHS/United States ; }, mesh = {*DNA Transformation Competence ; Evolution, Molecular ; Gene Transfer, Horizontal ; Genetic Variation ; Genome, Bacterial ; *Host Specificity ; Pasteurellaceae/*genetics/*physiology ; *Recombination, Genetic ; *Transformation, Genetic ; }, abstract = {UNLABELLED: Natural transformation by competent bacteria is a primary means of horizontal gene transfer; however, evidence that competence drives bacterial diversity and evolution has remained elusive. To test this theory, we used a retrospective comparative genomic approach to analyze the evolutionary history of Aggregatibacter actinomycetemcomitans, a bacterial species with both competent and noncompetent sister strains. Through comparative genomic analyses, we reveal that competence is evolutionarily linked to genomic diversity and speciation. Competence loss occurs frequently during evolution and is followed by the loss of clustered regularly interspaced short palindromic repeats (CRISPRs), bacterial adaptive immune systems that protect against parasitic DNA. Relative to noncompetent strains, competent bacteria have larger genomes containing multiple rearrangements. In contrast, noncompetent bacterial genomes are extremely stable but paradoxically susceptible to infective DNA elements, which contribute to noncompetent strain genetic diversity. Moreover, incomplete noncompetent strain CRISPR immune systems are enriched for self-targeting elements, which suggests that the CRISPRs have been co-opted for bacterial gene regulation, similar to eukaryotic microRNAs derived from the antiviral RNA interference pathway.<br><br>IMPORTANCE: The human microbiome is rich with thousands of diverse bacterial species. One mechanism driving this diversity is horizontal gene transfer by natural transformation, whereby naturally competent bacteria take up environmental DNA and incorporate new genes into their genomes. Competence is theorized to accelerate evolution; however, attempts to test this theory have proved difficult. Through genetic analyses of the human periodontal pathogen Aggregatibacter actinomycetemcomitans, we have discovered an evolutionary connection between competence systems promoting gene acquisition and CRISPRs (clustered regularly interspaced short palindromic repeats), adaptive immune systems that protect bacteria against genetic parasites. We show that competent A. actinomycetemcomitans strains have numerous redundant CRISPR immune systems, while noncompetent bacteria have lost their CRISPR immune systems because of inactivating mutations. Together, the evolutionary data linking the evolution of competence and CRISPRs reveals unique mechanisms promoting genetic heterogeneity and the rise of new bacterial species, providing insight into complex mechanisms underlying bacterial diversity in the human body.}, }
@article {pmid23028285, year = {2012}, author = {Friedman, J and Alm, EJ}, title = {Inferring correlation networks from genomic survey data.}, journal = {PLoS computational biology}, volume = {8}, number = {9}, pages = {e1002687}, pmid = {23028285}, issn = {1553-7358}, mesh = {Chromosome Mapping/*methods ; Computer Simulation ; *Genetics, Population ; Genome, Bacterial/*genetics ; Humans ; Microbial Consortia/*genetics ; *Models, Genetic ; Recombination, Genetic/*genetics ; Statistics as Topic ; }, abstract = {High-throughput sequencing based techniques, such as 16S rRNA gene profiling, have the potential to elucidate the complex inner workings of natural microbial communities - be they from the world's oceans or the human gut. A key step in exploring such data is the identification of dependencies between members of these communities, which is commonly achieved by correlation analysis. However, it has been known since the days of Karl Pearson that the analysis of the type of data generated by such techniques (referred to as compositional data) can produce unreliable results since the observed data take the form of relative fractions of genes or species, rather than their absolute abundances. Using simulated and real data from the Human Microbiome Project, we show that such compositional effects can be widespread and severe: in some real data sets many of the correlations among taxa can be artifactual, and true correlations may even appear with opposite sign. Additionally, we show that community diversity is the key factor that modulates the acuteness of such compositional effects, and develop a new approach, called SparCC (available at https://bitbucket.org/yonatanf/sparcc), which is capable of estimating correlation values from compositional data. To illustrate a potential application of SparCC, we infer a rich ecological network connecting hundreds of interacting species across 18 sites on the human body. Using the SparCC network as a reference, we estimated that the standard approach yields 3 spurious species-species interactions for each true interaction and misses 60% of the true interactions in the human microbiome data, and, as predicted, most of the erroneous links are found in the samples with the lowest diversity.}, }
@article {pmid23018494, year = {2012}, author = {Alan, G and Sarah, JP}, title = {Microbes as forensic indicators.}, journal = {Tropical biomedicine}, volume = {29}, number = {3}, pages = {311-330}, pmid = {23018494}, issn = {2521-9855}, mesh = {Animals ; Archaea/chemistry/*isolation &amp; purification ; Bacteria/chemistry/*isolation &amp; purification ; Body Fluids/chemistry/microbiology ; Cause of Death ; Coloring Agents/chemistry ; Communicable Diseases/mortality/transmission ; Female ; Forensic Medicine/*methods ; Humans ; *Microbiota ; Saliva/chemistry/microbiology ; Soil Microbiology ; }, abstract = {The forensic potential of microorganisms is becoming increasingly apparent as a consequence of advances in molecular sciences and genomics. This review discusses instances in which microbes, and in particular bacteria, can impact upon forensic investigations. There is increasing evidence that humans have an extremely diverse 'microbiome' that may prove useful in determining ethnicity, country of origin, and even personal identity. The human microbiome differs between regions of the body and may prove useful for determining the nature of stains such as those caused by saliva and vaginal fluid: it may even be possible to link the stains to the person responsible for them. Similarly, the composition of the microbiome present in a soil sample may prove a useful indicator of geographic origin or as a means of linking people, animals, or objects together or to a specific location. Microorganisms are important in the decay process and also influence the presence and concentration of alcohol, drugs, and other chemicals of forensic relevance. There is also a possibility that the entry of microorganisms into the body during the agonal period may prove useful for the diagnosis of drowning. The transmission of infectious diseases, and in particular sexually-transmitted diseases, can provide evidence linking a victim and a suspect. Microorganisms that cause fatal infections are not always identified at the time of death and may lead to the death being considered 'suspicious'. If a fatal infection can be linked to a hospital or medical procedure it can lead to prosecutions and therefore it is important to determine when and where an infection was acquired. Similarly, naturally acquired infections need to be distinguished from those that result from malicious transmission. Microorganisms can therefore provide evidence in many different forensic scenarios but most of the work is still at the experimental stage and there are therefore many opportunities for further research.}, }
@article {pmid23015740, year = {2012}, author = {Marinelli, LJ and Fitz-Gibbon, S and Hayes, C and Bowman, C and Inkeles, M and Loncaric, A and Russell, DA and Jacobs-Sera, D and Cokus, S and Pellegrini, M and Kim, J and Miller, JF and Hatfull, GF and Modlin, RL}, title = {Propionibacterium acnes bacteriophages display limited genetic diversity and broad killing activity against bacterial skin isolates.}, journal = {mBio}, volume = {3}, number = {5}, pages = {}, pmid = {23015740}, issn = {2150-7511}, support = {R21 AR060382/AR/NIAMS NIH HHS/United States ; T32 GM008042/GM/NIGMS NIH HHS/United States ; F32 AR060655/AR/NIAMS NIH HHS/United States ; R01 AR053542/AR/NIAMS NIH HHS/United States ; F32AR060655/AR/NIAMS NIH HHS/United States ; R21AR060382/AR/NIAMS NIH HHS/United States ; R01AR053542/AR/NIAMS NIH HHS/United States ; }, mesh = {*Bacteriolysis ; Bacteriophages/*classification/genetics/isolation &amp; purification/*physiology ; Base Composition ; DNA, Viral/chemistry/genetics ; Genes, Viral ; *Genetic Variation ; Genome, Viral ; Host Specificity ; Humans ; Molecular Sequence Data ; Propionibacterium acnes/*isolation &amp; purification/*virology ; Sebaceous Glands/microbiology/virology ; Sequence Analysis, DNA ; Sequence Homology, Nucleic Acid ; Skin/microbiology/virology ; Synteny ; }, abstract = {UNLABELLED: Investigation of the human microbiome has revealed diverse and complex microbial communities at distinct anatomic sites. The microbiome of the human sebaceous follicle provides a tractable model in which to study its dominant bacterial inhabitant, Propionibacterium acnes, which is thought to contribute to the pathogenesis of the human disease acne. To explore the diversity of the bacteriophages that infect P. acnes, 11 P. acnes phages were isolated from the sebaceous follicles of donors with healthy skin or acne and their genomes were sequenced. Comparative genomic analysis of the P. acnes phage population, which spans a 30-year temporal period and a broad geographic range, reveals striking similarity in terms of genome length, percent GC content, nucleotide identity (>85%), and gene content. This was unexpected, given the far-ranging diversity observed in virtually all other phage populations. Although the P. acnes phages display a broad host range against clinical isolates of P. acnes, two bacterial isolates were resistant to many of these phages. Moreover, the patterns of phage resistance correlate closely with the presence of clustered regularly interspaced short palindromic repeat elements in the bacteria that target a specific subset of phages, conferring a system of prokaryotic innate immunity. The limited diversity of the P. acnes bacteriophages, which may relate to the unique evolutionary constraints imposed by the lipid-rich anaerobic environment in which their bacterial hosts reside, points to the potential utility of phage-based antimicrobial therapy for acne.<br><br>IMPORTANCE: Propionibacterium acnes is a dominant member of the skin microflora and has also been implicated in the pathogenesis of acne; however, little is known about the bacteriophages that coexist with and infect this bacterium. Here we present the novel genome sequences of 11 P. acnes phages, thereby substantially increasing the amount of available genomic information about this phage population. Surprisingly, we find that, unlike other well-studied bacteriophages, P. acnes phages are highly homogeneous and show a striking lack of genetic diversity, which is perhaps related to their unique and restricted habitat. They also share a broad ability to kill clinical isolates of P. acnes; phage resistance is not prevalent, but when detected, it appears to be conferred by chromosomally encoded immunity elements within the host genome. We believe that these phages display numerous features that would make them ideal candidates for the development of a phage-based therapy for acne.}, }
@article {pmid23015504, year = {2012}, author = {Rogers, AB}, title = {Gastric Helicobacter spp. in animal models: pathogenesis and modulation by extragastric coinfections.}, journal = {Methods in molecular biology (Clifton, N.J.)}, volume = {921}, number = {}, pages = {175-188}, doi = {10.1007/978-1-62703-005-2_21}, pmid = {23015504}, issn = {1940-6029}, mesh = {Animals ; *Coinfection ; *Disease Models, Animal ; Helicobacter/*pathogenicity ; Helicobacter Infections/*complications/*microbiology ; Humans ; Stomach/*microbiology ; }, abstract = {Animal models are used to study complex host, microbial, and environmental influences associated with gastric Helicobacter infection. Evidence that gastric helicobacters are pathogenic in animals first came from ferrets. Felids, nonhuman primates, and many other species also harbor stomach helicobacters. Today, mice are preferred by most researchers for scientific investigation because of cost-efficiencies, rapid reproduction, choice of laboratory reagents, and availability of genetically engineered models. Infection with Helicobacter felis or H. pylori Sydney strain-1 in appropriate mouse strains produces disease with remarkable similarities to H. pylori in humans. Due to recent advances in genetic engineering, in vivo imaging, and system-wide genomics and proteomics, these models will become even more widespread in the future. Recently, it has been shown that extragastric infections can dramatically affect the severity of disease induced by gastric Helicobacter spp. through heterologous immunity. These models provide proof-of-principle for the "African enigma" wherein gastric cancer is underrepresented in low-lying tropical countries with concurrently high H. pylori and internal parasite prevalence. Helicobacter gastritis and carcinogenesis in mouse models may be augmented or ameliorated by other infectious agents depending on the character of the invoked immune response. Knowledge gained from the Human Microbiome Project and other investigations is certain to shed new light on the influence of extragastric bacterial, viral, fungal, and parasitic coinfections on H. pylori-associated peptic ulcer disease and gastric adenocarcinoma.}, }
@article {pmid23013527, year = {2012}, author = {Meyer, F and Trimble, WL and Chang, EB and Handley, KM}, title = {Functional predictions from inference and observation in sequence-based inflammatory bowel disease research.}, journal = {Genome biology}, volume = {13}, number = {9}, pages = {169}, pmid = {23013527}, issn = {1474-760X}, abstract = {Meta-omics approaches such as metagenomics, metatranscriptomics and metaproteogenomics have the potential to improve our understanding of how the human microbiome affects digestive health and disease.}, }
@article {pmid22699663, year = {2012}, author = {Divaris, K and Monda, KL and North, KE and Olshan, AF and Lange, EM and Moss, K and Barros, SP and Beck, JD and Offenbacher, S}, title = {Genome-wide association study of periodontal pathogen colonization.}, journal = {Journal of dental research}, volume = {91}, number = {7 Suppl}, pages = {21S-28S}, pmid = {22699663}, issn = {1544-0591}, support = {P30 ES010126/ES/NIEHS NIH HHS/United States ; R01 HL059367/HL/NHLBI NIH HHS/United States ; HHSN268201100007C/HL/NHLBI NIH HHS/United States ; HHSN268201100011I/HL/NHLBI NIH HHS/United States ; R01 ES014843/ES/NIEHS NIH HHS/United States ; U01HG004402/HG/NHGRI NIH HHS/United States ; HHSN268201100006C/HL/NHLBI NIH HHS/United States ; R01HL087641/HL/NHLBI NIH HHS/United States ; HHSN268201100007I/HL/NHLBI NIH HHS/United States ; P30ES010126/ES/NIEHS NIH HHS/United States ; UL1RR025005/RR/NCRR NIH HHS/United States ; R01DE021418/DE/NIDCR NIH HHS/United States ; HHSN268201100009I/HL/NHLBI NIH HHS/United States ; R01 DE011551/DE/NIDCR NIH HHS/United States ; R01HL59367/HL/NHLBI NIH HHS/United States ; HHSN268201100010C/HL/NHLBI NIH HHS/United States ; HSN268201100012C//PHS HHS/United States ; UL1 RR025005/RR/NCRR NIH HHS/United States ; HHSN268201100008C/HL/NHLBI NIH HHS/United States ; HHSN268201100005G/HL/NHLBI NIH HHS/United States ; HHSN268201100008I/HL/NHLBI NIH HHS/United States ; HHSN268201100011C/HL/NHLBI NIH HHS/United States ; R01 HL086694/HL/NHLBI NIH HHS/United States ; HHSN268200625226C//PHS HHS/United States ; U01 HG004402/HG/NHGRI NIH HHS/United States ; HHSN268201100005I/HL/NHLBI NIH HHS/United States ; R01DE11551/DE/NIDCR NIH HHS/United States ; HHSN268201100009C/HL/NHLBI NIH HHS/United States ; HHSN268201100005C/HL/NHLBI NIH HHS/United States ; R24 HD050924/HD/NICHD NIH HHS/United States ; R01 HL087641/HL/NHLBI NIH HHS/United States ; R01HL086694/HL/NHLBI NIH HHS/United States ; R01 DE021418/DE/NIDCR NIH HHS/United States ; }, mesh = {Aggregatibacter actinomycetemcomitans/classification/genetics ; Bacterial Load ; Bacteroides/classification/genetics ; Calcium-Binding Proteins/genetics ; Campylobacter rectus/classification/genetics ; Chronic Periodontitis/*microbiology ; Core Binding Factor Alpha 1 Subunit/genetics ; DNA, Bacterial/genetics ; DNA-Binding Proteins/genetics ; F-Box Proteins/genetics ; Female ; Fusobacterium nucleatum/classification/genetics ; Genetic Predisposition to Disease/genetics ; Genome-Wide Association Study ; Humans ; Interleukin-33 ; Interleukins/genetics ; Male ; Metagenome/*genetics ; Middle Aged ; Nucleic Acid Hybridization ; Periodontium/*microbiology ; Porphyromonas gingivalis/classification/genetics ; Potassium Channels, Tandem Pore Domain/genetics ; Prevotella intermedia/classification/genetics ; Prevotella nigrescens/classification/genetics ; Repressor Proteins ; Trans-Activators/genetics ; Transcription Factors/genetics ; Treponema denticola/classification/genetics ; Ubiquitin-Protein Ligases/genetics ; Vesicle-Associated Membrane Protein 3/genetics ; Zinc Fingers/genetics ; }, abstract = {Pathological shifts of the human microbiome are characteristic of many diseases, including chronic periodontitis. To date, there is limited evidence on host genetic risk loci associated with periodontal pathogen colonization. We conducted a genome-wide association (GWA) study among 1,020 white participants of the Atherosclerosis Risk in Communities Study, whose periodontal diagnosis ranged from healthy to severe chronic periodontitis, and for whom "checkerboard" DNA-DNA hybridization quantification of 8 periodontal pathogens was performed. We examined 3 traits: "high red" and "high orange" bacterial complexes, and "high" Aggregatibacter actinomycetemcomitans (Aa) colonization. Genotyping was performed on the Affymetrix 6.0 platform. Imputation to 2.5 million markers was based on HapMap II-CEU, and a multiple-test correction was applied (genome-wide threshold of p < 5 × 10(-8)). We detected no genome-wide significant signals. However, 13 loci, including KCNK1, FBXO38, UHRF2, IL33, RUNX2, TRPS1, CAMTA1, and VAMP3, provided suggestive evidence (p < 5 × 10(-6)) of association. All associations reported for "red" and "orange" complex microbiota, but not for Aa, had the same effect direction in a second sample of 123 African-American participants. None of these polymorphisms was associated with periodontitis diagnosis. Investigations replicating these findings may lead to an improved understanding of the complex nature of host-microbiome interactions that characterizes states of health and disease.}, }
@article {pmid22971068, year = {2012}, author = {Taube, C and Müller, A}, title = {The role of Helicobacter pylori infection in the development of allergic asthma.}, journal = {Expert review of respiratory medicine}, volume = {6}, number = {4}, pages = {441-449}, doi = {10.1586/ers.12.40}, pmid = {22971068}, issn = {1747-6356}, mesh = {Asthma/epidemiology/*physiopathology/prevention &amp; control ; Helicobacter Infections/epidemiology/*physiopathology ; Helicobacter pylori/*physiology ; Humans ; Hypersensitivity/epidemiology/*physiopathology/prevention &amp; control ; Metagenome/immunology ; Prevalence ; T-Lymphocytes, Regulatory/physiology ; }, abstract = {Asthma is one of the most prevalent chronic diseases in developed countries, with steady increases in asthma prevalence evident, particularly in the last few decades. As genetic factors are unlikely to contribute to the rise in asthma prevalence, changes in lifestyle and exposure to environmental stimuli have been proposed to account for this trend. The 'disappearing microbiota' hypothesis postulates that major shifts in the human microbiome, resulting from dramatic lifestyle changes, account for the increase in asthma prevalence. In this context, persistent gastric colonization with the human-specific pathogen Helicobacter pylori has been negatively associated with the occurrence of asthma in epidemiological studies. In addition, experimental models of allergic airway disease revealed a direct link between infection with H. pylori and suppression of allergic airway disease through the induction of regulatory T cells. These and other new insights hold the promise of opening up new avenues toward the development of innovative, new strategies directed at asthma treatment and prevention.}, }
@article {pmid22962617, year = {2012}, author = {Flores, GE and Henley, JB and Fierer, N}, title = {A direct PCR approach to accelerate analyses of human-associated microbial communities.}, journal = {PloS one}, volume = {7}, number = {9}, pages = {e44563}, pmid = {22962617}, issn = {1932-6203}, mesh = {Bacteria/classification/*genetics ; DNA, Bacterial/*analysis/genetics ; Feces/microbiology ; Humans ; Metagenome/*genetics ; Microbial Consortia/*genetics ; Mouth/microbiology ; Phylogeny ; Polymerase Chain Reaction/*methods ; RNA, Ribosomal, 16S/*analysis/genetics ; Reagent Kits, Diagnostic ; Skin/microbiology ; }, abstract = {Since the composition of the human microbiome is highly variable both within and between individuals, researchers are increasingly reliant on high-throughput molecular approaches to identify linkages between the composition of these communities and human health. While new sequencing technologies have made it increasingly feasible to analyze large numbers of human-associated samples, the extraction of DNA from samples often remains a bottleneck in the process. Here we tested a direct PCR approach using the Extract-N-Amp Plant PCR Kit to accelerate the 16S rRNA gene-based analyses of human-associated bacterial communities, directly comparing this method to a more commonly-used approach whereby DNA is first extracted and purified from samples using a series of steps prior to PCR amplification. We used both approaches on replicate samples collected from each of five body habitats (tongue surface, feces, forehead skin, underarm skin, and forearm skin) from four individuals. With the exception of the tongue samples, there were few significant differences in the estimates of taxon richness or phylogenetic diversity obtained using the two approaches. Perhaps more importantly, there were no significant differences between the methods in their ability resolve body habitat differences or inter-individual differences in bacterial community composition and the estimates of the relative abundances of individual taxa were nearly identical with the two methods. Overall, the two methods gave very similar results and the direct PCR approach is clearly advantageous for many studies exploring the diversity and composition of human-associated bacterial communities given that large numbers of samples can be processed far more quickly and efficiently.}, }
@article {pmid22941505, year = {2012}, author = {Hajishengallis, G and Darveau, RP and Curtis, MA}, title = {The keystone-pathogen hypothesis.}, journal = {Nature reviews. Microbiology}, volume = {10}, number = {10}, pages = {717-725}, pmid = {22941505}, issn = {1740-1534}, support = {DE18274/DE/NIDCR NIH HHS/United States ; RC4 DE021580/DE/NIDCR NIH HHS/United States ; R01 DE015254/DE/NIDCR NIH HHS/United States ; G0900408/MRC_/Medical Research Council/United Kingdom ; DE021685/DE/NIDCR NIH HHS/United States ; DE018292/DE/NIDCR NIH HHS/United States ; DE015254/DE/NIDCR NIH HHS/United States ; R01 DE018274/DE/NIDCR NIH HHS/United States ; R01 DE021685/DE/NIDCR NIH HHS/United States ; R01 DE018292/DE/NIDCR NIH HHS/United States ; DE021580/DE/NIDCR NIH HHS/United States ; MR/J011118/1/MRC_/Medical Research Council/United Kingdom ; R01 DE012768/DE/NIDCR NIH HHS/United States ; DE012768/DE/NIDCR NIH HHS/United States ; }, mesh = {Bacteria/*pathogenicity ; Colonic Neoplasms/microbiology ; Host-Pathogen Interactions ; Humans ; Inflammation/*microbiology ; Inflammatory Bowel Diseases/microbiology ; *Metagenome ; Microbial Interactions ; *Models, Biological ; Periodontitis/microbiology ; }, abstract = {Recent studies have highlighted the importance of the human microbiome in health and disease. However, for the most part the mechanisms by which the microbiome mediates disease, or protection from it, remain poorly understood. The keystone-pathogen hypothesis holds that certain low-abundance microbial pathogens can orchestrate inflammatory disease by remodelling a normally benign microbiota into a dysbiotic one. In this Opinion article, we critically assess the available literature that supports this hypothesis, which may provide a novel conceptual basis for the development of targeted diagnostics and treatments for complex dysbiotic diseases.}, }
@article {pmid22925763, year = {2012}, author = {Lujan, DK and Stanziale, JA and Mostafavi, AZ and Sharma, S and Troutman, JM}, title = {Chemoenzymatic synthesis of an isoprenoid phosphate tool for the analysis of complex bacterial oligosaccharide biosynthesis.}, journal = {Carbohydrate research}, volume = {359}, number = {}, pages = {44-53}, pmid = {22925763}, issn = {1873-426X}, support = {R15 GM100402/GM/NIGMS NIH HHS/United States ; R15GM100402/GM/NIGMS NIH HHS/United States ; }, mesh = {Acetylgalactosamine/chemistry ; Alkyl and Aryl Transferases/genetics/isolation &amp; purification/*metabolism ; Bacteroides fragilis/*enzymology/metabolism ; Biocatalysis ; Campylobacter jejuni/enzymology ; Chemistry Techniques, Synthetic ; Glycosyltransferases/metabolism ; Oligosaccharides/*biosynthesis ; Polyisoprenyl Phosphates/*chemical synthesis/chemistry/metabolism ; Sesquiterpenes/metabolism ; }, abstract = {Undecaprenyl Pyrophosphate Synthase (UPPS) is a key enzyme that catalyzes the production of bactoprenols, which act as membrane anchors for the assembly of complex bacterial oligosaccharides. One of the major hurdles in understanding the assembly of oligosaccharide assembly is a lack of chemical tools to study this process, since bactoprenols and the resulting isoprenoid-linked oligosaccharides lack handles or chromophores for use in pathway analysis. Here we describe the isolation of a new UPPS from the symbiotic microorganism Bacteroides fragilis, a key species in the human microbiome. The protein was purified to homogeneity and utilized to accept a chromophore containing farnesyl diphosphate analogue as a substrate. The analogue was utilized by the enzyme and resulted in a bactoprenyl diphosphate product with an easy to monitor tag associated with it. Furthermore, the diphosphate is shown to be readily converted to monophosphate using a common molecular biology reagent. This monophosphate product allowed for the investigation of complex oligosaccharide biosynthesis, and was used to probe the activity of glycosyltransferases involved in the well characterized Campylobacter jejuni N-linked protein glycosylation. Novel reagents similar to this will provide key tools for the study of uncharacterized oligosaccharide assemblies, and open the possibility for the development of rapid screening methodology for these biosynthetic systems.}, }
@article {pmid22904687, year = {2012}, author = {Gevers, D and Knight, R and Petrosino, JF and Huang, K and McGuire, AL and Birren, BW and Nelson, KE and White, O and Methé, BA and Huttenhower, C}, title = {The Human Microbiome Project: a community resource for the healthy human microbiome.}, journal = {PLoS biology}, volume = {10}, number = {8}, pages = {e1001377}, pmid = {22904687}, issn = {1545-7885}, support = {U54 HG004973/HG/NHGRI NIH HHS/United States ; U54HG004969/HG/NHGRI NIH HHS/United States ; U54 HG003067/HG/NHGRI NIH HHS/United States ; P30 DK043351/DK/NIDDK NIH HHS/United States ; R01HG004872/HG/NHGRI NIH HHS/United States ; U54 AI084844/AI/NIAID NIH HHS/United States ; U54HG004973/HG/NHGRI NIH HHS/United States ; R01 HG004872/HG/NHGRI NIH HHS/United States ; R01 HG005969/HG/NHGRI NIH HHS/United States ; U54 HG004969/HG/NHGRI NIH HHS/United States ; R01HG005969/HG/NHGRI NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; U01HG004866/HG/NHGRI NIH HHS/United States ; U01 HG004866/HG/NHGRI NIH HHS/United States ; U54AI084844/AI/NIAID NIH HHS/United States ; }, mesh = {Computational Biology ; Ecosystem ; Genes, rRNA ; *Genomics ; Health ; High-Throughput Nucleotide Sequencing ; Humans ; *Internet ; *Metagenome ; Organizations/*organization &amp; administration ; Phylogeny ; RNA, Ribosomal, 16S/analysis/genetics ; }, abstract = {This manuscript describes the NIH Human Microbiome Project, including a brief review of human microbiome research, a history of the project, and a comprehensive overview of the consortium's recent collection of publications analyzing the human microbiome.}, }
@article {pmid22903626, year = {2013}, author = {Gupta, A and Terrell, JL and Fernandes, R and Dowling, MB and Payne, GF and Raghavan, SR and Bentley, WE}, title = {Encapsulated fusion protein confers "sense and respond" activity to chitosan-alginate capsules to manipulate bacterial quorum sensing.}, journal = {Biotechnology and bioengineering}, volume = {110}, number = {2}, pages = {552-562}, doi = {10.1002/bit.24711}, pmid = {22903626}, issn = {1097-0290}, mesh = {Alginates/chemistry ; Animals ; Antibodies ; Bioengineering/*methods ; Cattle ; Chitosan/chemistry ; Escherichia coli/*drug effects/*physiology ; Glucuronic Acid/chemistry ; Green Fluorescent Proteins/chemistry ; Hexuronic Acids/chemistry ; Homoserine/analogs &amp; derivatives/chemistry/pharmacology ; Lactones/chemistry/pharmacology ; *Nanocapsules ; Nanotechnology/*methods ; Polyphosphates ; Quorum Sensing/*drug effects ; Recombinant Fusion Proteins/chemistry/*pharmacology ; S-Adenosylhomocysteine ; Serum Albumin, Bovine/chemistry ; }, abstract = {We demonstrate that "nanofactory"-loaded biopolymer capsules placed in the midst of a bacterial population can direct bacterial communication. Quorum sensing (QS) is a process by which bacteria communicate through small-molecules, such as autoinducer-2 (AI-2), leading to collective behaviors such as virulence and biofilm formation. In our approach, a "nanofactory" construct is created, which comprises an antibody complexed with a fusion protein that produces AI-2. These nanofactories are entrapped within capsules formed by electrostatic complexation of cationic (chitosan) and anionic (sodium alginate) biopolymers. The chitosan capsule shell is crosslinked by tripolyphosphate (TPP) to confer structural integrity. The capsule shell is impermeable to the encapsulated nanofactories, but freely permeable to small molecules. In turn, the capsules are able to take in substrates from the external medium via diffusion, and convert these via the nanofactories into AI-2, which then diffuses out. The exported AI-2 is shown to stimulate QS responses in vicinal Escherichia coli. Directing bacterial population behavior has potential applications in next-generation antimicrobial therapy and pathogen detection. We also envision such capsules to be akin to artificial "cells" that can participate in native biological signaling and communicate in real-time with the human microbiome. Through such interaction capabilities, these "cells" may sense the health of the microbiome, and direct its function in a desired, host-friendly manner.}, }
@article {pmid22902418, year = {2012}, author = {Triggle, DJ}, title = {Nous sommes tous des bacteries: implications for medicine, pharmacology and public health.}, journal = {Biochemical pharmacology}, volume = {84}, number = {12}, pages = {1543-1550}, doi = {10.1016/j.bcp.2012.08.005}, pmid = {22902418}, issn = {1873-2968}, mesh = {*Bacteria ; Humans ; *Metagenome ; *Pharmacology ; *Public Health ; }, abstract = {As a species we humans are outnumbered by bacteria in both cell and gene count. This somewhat humbling observation is key to the increasing recognition that the long-standing symbiotic and commensal relations between Homo sapiens and bacteria are of great significance to basic human physiology and health. Knowledge of our human bacterial environment is contributing to an understanding of a variety of disorders including obesity and metabolic syndrome, cardiovascular disease, immunity, and neuronal development and behavior. The Human Microbiome Project is providing a genetic and ecological analysis and will serve as a parallel to the Human Genome Project. Exploration of the chemical space utilized by bacteria will contribute to the development of new small molecule therapeutic agents, including new antibiotics. And genetically re-engineered bacteria are proving to be of potential value as actual therapeutic entities. Our understanding of our bacterial world has the capability to transform radically our current approach to human health diverting it from an emphasis on acute treatments to living in healthy harmony with both our internal and external environments.}, }
@article {pmid22900013, year = {2012}, author = {Minot, S and Wu, GD and Lewis, JD and Bushman, FD}, title = {Conservation of gene cassettes among diverse viruses of the human gut.}, journal = {PloS one}, volume = {7}, number = {8}, pages = {e42342}, pmid = {22900013}, issn = {1932-6203}, support = {T32 AI060516/AI/NIAID NIH HHS/United States ; UH2 DK083981/DK/NIDDK NIH HHS/United States ; UH2DK083981/DK/NIDDK NIH HHS/United States ; T32AI060516/AI/NIAID NIH HHS/United States ; }, mesh = {Bacteriophages/genetics/metabolism ; Computational Biology/methods ; Conserved Sequence ; Contig Mapping ; Genome, Viral ; Humans ; Intestines/microbiology/*virology ; Metagenome/*genetics ; Open Reading Frames ; Viral Proteins/genetics ; }, abstract = {Viruses are a crucial component of the human microbiome, but large population sizes, high sequence diversity, and high frequencies of novel genes have hindered genomic analysis by high-throughput sequencing. Here we investigate approaches to metagenomic assembly to probe genome structure in a sample of 5.6 Gb of gut viral DNA sequence from six individuals. Tests showed that a new pipeline based on DeBruijn graph assembly yielded longer contigs that were able to recruit more reads than the equivalent non-optimized, single-pass approach. To characterize gene content, the database of viral RefSeq proteins was compared to the assembled viral contigs, generating a bipartite graph with functional cassettes linking together viral contigs, which revealed a high degree of connectivity between diverse genomes involving multiple genes of the same functional class. In a second step, open reading frames were grouped by their co-occurrence on contigs in a database-independent manner, revealing conserved cassettes of co-oriented ORFs. These methods reveal that free-living bacteriophages, while usually dissimilar at the nucleotide level, often have significant similarity at the level of encoded amino acid motifs, gene order, and gene orientation. These findings thus connect contemporary metagenomic analysis with classical studies of bacteriophage genomic cassettes. Software is available at https://sourceforge.net/projects/optitdba/.}, }
@article {pmid22897827, year = {2012}, author = {Dridi, B}, title = {Laboratory tools for detection of archaea in humans.}, journal = {Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases}, volume = {18}, number = {9}, pages = {825-833}, doi = {10.1111/j.1469-0691.2012.03952.x}, pmid = {22897827}, issn = {1469-0691}, mesh = {Archaea/genetics/*isolation &amp; purification ; Feces/microbiology ; Humans ; *Metagenome ; Methanobacteriaceae/isolation &amp; purification ; Microbiological Techniques/*methods ; Mucous Membrane/microbiology ; }, abstract = {This work represents an update of knowledge regarding the detection methods for human microbiome-associated archaea. Despite the fact that, during the last three decades, only four methanoarchaeal species have been isolated from the human mucosa, including faeces, subgingival plaque, and vaginal mucosa (Methanobrevibacter smithii, Methanosphaera stadtmanae, Methanobrevibacter oralis and, most recently, 'Methanomassiliicoccus luminyensis'), molecular studies, including PCR and metagenomic analyses, have detected DNA sequences indicative of the presence of additional methanoarchaea, as well as non-methanogenic archaea, in the human intestinal tract. Opinion is divided on the roles (if any) of these organisms in human disease, and certainly the data are still unclear. Future research and recently reported data highlighting the antimicrobial susceptibility of the human methanoarchaea could help in the design of selective media to discover additional human mucosa-associated archaea and ascertain their role in human infections involving complex flora.}, }
@article {pmid22861809, year = {2012}, author = {James, WP and Garza, C}, title = {Summary of the 24(th) Marabou Symposium: Nutrition and the human microbiome.}, journal = {Nutrition reviews}, volume = {70 Suppl 1}, number = {}, pages = {S87-94}, doi = {10.1111/j.1753-4887.2012.00497.x}, pmid = {22861809}, issn = {1753-4887}, mesh = {*Congresses as Topic ; Gastrointestinal Tract/*microbiology ; *Health Status ; Humans ; Metagenome/*physiology ; Nutritional Physiological Phenomena/*physiology ; }, abstract = {This summary covers the articles and attributed discussion in the present supplement, which resulted from the 24(th) Marabou Symposium titled "Nutrition and the Human Microbiome", which was held in Stockholm in 2011 with the participation of about 40 global experts in microbiology, physiology, biology, and medicine. The individual articles address a number of topics related to the human microbiome; the attributed discussion, however, offers much more on the nature of the current scientific debate and provides insight into new opportunities for research as well as possible effects of the gut microbes, ranging from possible prenatal epigenetic effects to brain function and behavior.}, }
@article {pmid22861808, year = {2012}, author = {}, title = {Discussion from the 24(th) Marabou Symposium: Nutrition and the human microbiome.}, journal = {Nutrition reviews}, volume = {70 Suppl 1}, number = {}, pages = {S57-86}, doi = {10.1111/j.1753-4887.2012.00501.x}, pmid = {22861808}, issn = {1753-4887}, mesh = {Congresses as Topic ; Humans ; Metagenome/*physiology ; Nutritional Physiological Phenomena/*physiology ; }, }
@article {pmid22861806, year = {2012}, author = {Ursell, LK and Metcalf, JL and Parfrey, LW and Knight, R}, title = {Defining the human microbiome.}, journal = {Nutrition reviews}, volume = {70 Suppl 1}, number = {Suppl 1}, pages = {S38-44}, pmid = {22861806}, issn = {1753-4887}, support = {HG4872/HG/NHGRI NIH HHS/United States ; T32 GM008759/GM/NIGMS NIH HHS/United States ; R01 HG004872/HG/NHGRI NIH HHS/United States ; T32 GM142607/GM/NIGMS NIH HHS/United States ; /HHMI_/Howard Hughes Medical Institute/United States ; }, mesh = {Bacteria/*classification/*genetics ; Biodiversity ; Gastrointestinal Tract/*microbiology ; Humans ; Metagenome/*genetics ; Phylogeny ; RNA, Ribosomal, 16S/analysis ; Sequence Analysis ; }, abstract = {Rapidly developing sequencing methods and analytical techniques are enhancing our ability to understand the human microbiome, and, indeed, how the microbiome and its constituents are defined. This review highlights recent research that expands our ability to understand the human microbiome on different spatial and temporal scales, including daily time series datasets spanning months. Furthermore, emerging concepts related to defining operational taxonomic units, diversity indices, core versus transient microbiomes, and the possibility of enterotypes are discussed. Additional advances in sequencing technology and in our understanding of the microbiome will provide exciting prospects for exploiting the microbiota for personalized medicine.}, }
@article {pmid22861804, year = {2012}, author = {Relman, DA}, title = {The human microbiome: ecosystem resilience and health.}, journal = {Nutrition reviews}, volume = {70 Suppl 1}, number = {Suppl 1}, pages = {S2-9}, pmid = {22861804}, issn = {1753-4887}, support = {DP1 OD000964/OD/NIH HHS/United States ; DP1 OD000964-05/OD/NIH HHS/United States ; DP1OD000964/OD/NIH HHS/United States ; }, mesh = {Anti-Bacterial Agents/*pharmacology ; Biodiversity ; *Ecosystem ; Gastrointestinal Tract/*microbiology ; Humans ; *Metagenome/drug effects ; Phylogeny ; Species Specificity ; Symbiosis ; }, abstract = {Given the importance of the microbiome for human health, both the stability and the response to disturbance of this microbial ecosystem are crucial issues. Yet, the current understanding of these factors is insufficient. Early data suggest there is relative stability in the microbiome of adults in the absence of gross perturbation, and that long-term stability of the human indigenous microbial communities is maintained not by inertia but by the action of restorative forces within a dynamic system. After brief exposures to some antibiotics, there is an immediate and substantial perturbation and at least a partial recovery of taxonomic composition. Responses to antibiotics are individualized and are influenced by prior experience with the same antibiotic. These findings suggest that the human microbiome has properties of resilience. Besides serving to reveal critical underlying functional attributes, microbial interactions, and keystone species within the indigenous microbiota, the response to disturbance may have value in predicting future instability and disease and in managing the human microbial ecosystem.}, }
@article {pmid22861802, year = {2012}, author = {Bäckhed, F}, title = {Host responses to the human microbiome.}, journal = {Nutrition reviews}, volume = {70 Suppl 1}, number = {}, pages = {S14-7}, doi = {10.1111/j.1753-4887.2012.00496.x}, pmid = {22861802}, issn = {1753-4887}, mesh = {Animals ; Bacterial Physiological Phenomena ; Gastrointestinal Tract/*microbiology ; Germ-Free Life ; Humans ; Inflammatory Bowel Diseases/etiology/*microbiology ; Metagenome/*physiology ; Mice ; Obesity/etiology/*microbiology ; }, abstract = {The human gut is home to vast numbers of bacteria (gut microbiota), which outnumber the cells in the human body by an order of magnitude. The gut microbiota has coevolved with humans and can be considered an organ of similar size as the liver, containing more than 1,000 cell types (bacterial species) and encoding 150-fold more genes than are present in the human genome. Accordingly, the gut microbiota may have profound effects on various host responses, either directly or indirectly, by modifying food components or endogenously produced molecules into signaling molecules. Recent findings suggest that an altered gut microbial composition is associated with inflammatory bowel disease and obesity, indicating that the gut microbiota should be considered a contributing factor in several common diseases.}, }
@article {pmid22861801, year = {2012}, author = {Flint, HJ}, title = {The impact of nutrition on the human microbiome.}, journal = {Nutrition reviews}, volume = {70 Suppl 1}, number = {}, pages = {S10-3}, doi = {10.1111/j.1753-4887.2012.00499.x}, pmid = {22861801}, issn = {1753-4887}, mesh = {Bacteria/*growth &amp; development/metabolism ; Colon/microbiology ; Diet ; Dietary Carbohydrates/metabolism/pharmacology ; Dietary Fiber/*metabolism/microbiology ; Fermentation ; Gastrointestinal Tract/*microbiology ; Humans ; Metagenome/*physiology ; Nutritional Physiological Phenomena/*physiology ; Prebiotics ; Probiotics ; }, abstract = {Diet-derived carbohydrates that are not fully digested in the upper gut, known as nondigestible carbohydrates, provide a major source of energy for bacteria that colonize the human large intestine. It is well established that dietary intake of nondigestible carbohydrates influences microbial fermentation and total bacterial numbers in the colon. Recent evidence from molecular ecology has also shown that the amount and type of nondigestible carbohydrates (e.g., resistant starch, non-starch polysaccharides, and prebiotics) influences the species composition of the intestinal microbiota both in short-term dietary interventions and in response to habitual long-term dietary intake. Interindividual variation in gut microbiota may, in part, reflect differences in dietary intake, but the response of the gut microbiota to dietary change can also differ among individuals. As a better understanding is gained of the impact of different groups of bacteria on host metabolism, the ability to manipulate the microbiota through diet should provide a route for delivering health benefits.}, }
@article {pmid22861800, year = {2012}, author = {James, WP and Garza, C and , }, title = {Nutrition and Human Microbiome: 24 th Marabou Symposium, Stockholm, Sweden. Foreword.}, journal = {Nutrition reviews}, volume = {70 Suppl 1}, number = {}, pages = {S1}, doi = {10.1111/j.1753-4887.2012.00511.x}, pmid = {22861800}, issn = {1753-4887}, mesh = {Gastrointestinal Tract/*microbiology ; Humans ; *Metagenome ; Nutritional Physiological Phenomena/*physiology ; }, }
@article {pmid22890355, year = {2012}, author = {Yip, YL}, title = {Unlocking the potential of electronic health records for translational research. Findings from the section on bioinformatics and translational informatics.}, journal = {Yearbook of medical informatics}, volume = {7}, number = {}, pages = {135-138}, pmid = {22890355}, issn = {2364-0502}, mesh = {Awards and Prizes ; Biological Specimen Banks ; *Computational Biology ; Electronic Health Records ; Humans ; Medical Informatics ; Prospective Studies ; Societies, Medical ; *Translational Research, Biomedical ; }, abstract = {OBJECTIVES: To review current excellent research and trend in the field of bioinformatics and translational informatics with direct application in the medical domain.<br><br>METHOD: Synopsis of the articles selected for the IMIA Yearbook 2012.<br><br>RESULTS: Six excellent articles were selected in this Yearbook's section on Bioinformatics and Translational Informatics. They exemplify current key advances in the use of patient information for translational research and health surveillance. First, two proof-of-concept studies demonstrated the cross-institutional and -geographic use of Electronic Health Records (EHR) for clinical trial subjects identification and drug safety signals detection. These reports pave ways to global large-scale population monitoring. Second, there is further evidence on the importance of coupling phenotypic information in EHR with genotypic information (either in biobank or in gene association studies) for new biomedical knowledge discovery. Third, patient data gathered via social media and self-reporting was found to be comparable to existent data and less labor intensive. This alternative means could potentially overcome data collection challenge in cohort and prospective studies. Finally, it can be noted that metagenomic studies are gaining momentum in bioinformatics and system-level analysis of human microbiome sheds important light on certain human diseases.<br><br>CONCLUSIONS: The current literature showed that the traditional bench to bedside translational research is increasing being complemented by the reverse approach, in which bedside information can be used to provide novel biomedical insights.}, }
@article {pmid22853944, year = {2012}, author = {Highlander, SK}, title = {High throughput sequencing methods for microbiome profiling: application to food animal systems.}, journal = {Animal health research reviews}, volume = {13}, number = {1}, pages = {40-53}, doi = {10.1017/S1466252312000126}, pmid = {22853944}, issn = {1475-2654}, mesh = {Animals ; Animals, Domestic/*microbiology ; Archaea/genetics ; Bacteria/classification/genetics ; DNA, Ribosomal/chemistry/*genetics ; Genes, rRNA ; High-Throughput Nucleotide Sequencing/methods/*veterinary ; Humans ; Meat ; *Metagenome ; Metagenomics/*methods ; RNA, Ribosomal, 16S/*genetics ; Sequence Analysis, RNA/veterinary ; Viruses/genetics ; }, abstract = {Analysis of microbial communities using high throughput sequencing methods began in the mid 2000s permitting the production of 1000s to 10,000s of sequence reads per sample and megabases of data per sequence run. This then unprecedented depth of sequencing allowed, for the first time, the discovery of the 'rare biosphere' in environmental samples. The technology was quickly applied to studies in several human subjects. Perhaps these early studies served as a reminder that though the microbes that inhabit mammals are known to outnumber host cells by an order of magnitude or more, most of these are unknown members of our second genome, or microbiome (as coined by Joshua Lederberg), because of our inability to culture them. High throughput methods for microbial 16S ribosomal RNA gene and whole genome shotgun (WGS) sequencing have now begun to reveal the composition and identity of archaeal, bacterial and viral communities at many sites, in and on the human body. Surveys of the microbiota of food production animals have been published in the past few years and future studies should benefit from protocols and tools developed from large-scale human microbiome studies. Nevertheless, production animal-related resources, such as improved host genome assemblies and increased numbers and diversity of host-specific microbial reference genome sequences, will be needed to permit meaningful and robust analysis of 16S rDNA and WGS sequence data.}, }
@article {pmid22850148, year = {2012}, author = {}, title = {Educational advantage.}, journal = {Journal of empirical research on human research ethics : JERHRE}, volume = {7}, number = {3}, pages = {93}, doi = {10.1525/jer.2012.7.3.93}, pmid = {22850148}, issn = {1556-2654}, mesh = {Biomedical Research/*ethics ; *Ethics, Research ; Humans ; }, abstract = {Emerging issues in human research challenge us to think outside of the box. The first three papers in this issue provide such challenges. New ethical issues arise in connection with research on the human microbiome, sham surgery, and the use of psychotherapy in research interventions in tribal cultures in Kenya.}, }
@article {pmid22850139, year = {2012}, author = {McGuire, AL and Achenbaum, LS and Whitney, SN and Slashinski, MJ and Versalovic, J and Keitel, WA and McCurdy, SA}, title = {Perspectives on human microbiome research ethics.}, journal = {Journal of empirical research on human research ethics : JERHRE}, volume = {7}, number = {3}, pages = {1-14}, pmid = {22850139}, issn = {1556-2654}, support = {R01 HG004853/HG/NHGRI NIH HHS/United States ; R01HG004853/HG/NHGRI NIH HHS/United States ; }, mesh = {Adult ; Aged ; *Ethics, Research ; Female ; Humans ; Information Dissemination ; Informed Consent ; Interviews as Topic ; Male ; *Metagenome ; Metagenomics/*ethics/legislation &amp; jurisprudence ; Middle Aged ; National Institutes of Health (U.S.) ; Research Personnel ; Research Subjects ; United States ; }, abstract = {Study of ethical, legal, and social implications (ELSI) of human microbiome research has been integral to the Human Microbiome Project (HMP). This study explores core ELSI issues that arose during the first phase of the HMP from the perspective of individuals involved in the research. We conducted semi-structured in-depth interviews with investigators and NIH employees ("investigators") involved in the HMP, and with individuals recruited to participate in the HMP Healthy Cohort Study at Baylor College of Medicine ("recruits"). We report findings related to three major ELSI issues: informed consent, data sharing, and return of results. Our findings demonstrate that investigators and recruits were similarly sensitive to these issues yet generally comfortable with study design in light of current knowledge about the microbiome.}, }
@article {pmid22848458, year = {2012}, author = {Fodor, AA and DeSantis, TZ and Wylie, KM and Badger, JH and Ye, Y and Hepburn, T and Hu, P and Sodergren, E and Liolios, K and Huot-Creasy, H and Birren, BW and Earl, AM}, title = {The "most wanted" taxa from the human microbiome for whole genome sequencing.}, journal = {PloS one}, volume = {7}, number = {7}, pages = {e41294}, pmid = {22848458}, issn = {1932-6203}, support = {U54HG004969/HG/NHGRI NIH HHS/United States ; HHSN272200900018C/AI/NIAID NIH HHS/United States ; HHSN272200900008C/AI/NIAID NIH HHS/United States ; HHSN272200900001C/AI/NIAID NIH HHS/United States ; U54 HG004968/HG/NHGRI NIH HHS/United States ; HHSN2722009000018C//PHS HHS/United States ; U54 HG004969/HG/NHGRI NIH HHS/United States ; U54HG004968/HG/NHGRI NIH HHS/United States ; }, mesh = {Bacteria/*classification/*genetics ; Cohort Studies ; Female ; *Genes, Bacterial ; Genes, rRNA/*genetics ; Humans ; Male ; Metagenome/*genetics ; RNA, Bacterial/genetics ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA/*methods ; }, abstract = {The goal of the Human Microbiome Project (HMP) is to generate a comprehensive catalog of human-associated microorganisms including reference genomes representing the most common species. Toward this goal, the HMP has characterized the microbial communities at 18 body habitats in a cohort of over 200 healthy volunteers using 16S rRNA gene (16S) sequencing and has generated nearly 1,000 reference genomes from human-associated microorganisms. To determine how well current reference genome collections capture the diversity observed among the healthy microbiome and to guide isolation and future sequencing of microbiome members, we compared the HMP's 16S data sets to several reference 16S collections to create a 'most wanted' list of taxa for sequencing. Our analysis revealed that the diversity of commonly occurring taxa within the HMP cohort microbiome is relatively modest, few novel taxa are represented by these OTUs and many common taxa among HMP volunteers recur across different populations of healthy humans. Taken together, these results suggest that it should be possible to perform whole-genome sequencing on a large fraction of the human microbiome, including the 'most wanted', and that these sequences should serve to support microbiome studies across multiple cohorts. Also, in stark contrast to other taxa, the 'most wanted' organisms are poorly represented among culture collections suggesting that novel culture- and single-cell-based methods will be required to isolate these organisms for sequencing.}, }
@article {pmid22841660, year = {2012}, author = {Liu, L and Chen, X and Skogerbø, G and Zhang, P and Chen, R and He, S and Huang, DW}, title = {The human microbiome: a hot spot of microbial horizontal gene transfer.}, journal = {Genomics}, volume = {100}, number = {5}, pages = {265-270}, doi = {10.1016/j.ygeno.2012.07.012}, pmid = {22841660}, issn = {1089-8646}, mesh = {*Biota ; Computational Biology ; Gene Transfer, Horizontal/*genetics ; Genes, Bacterial/*genetics ; Genomics/*methods ; Humans ; Metagenome/*genetics ; Molecular Sequence Annotation ; }, abstract = {The human body harbors numerous microbes, and here exists a close relationship between microbes and human health. The Human Microbiome Project has generated whole genome sequences of several hundred human microbes. In this study, we identified horizontal gene transfer (HGT) events in human microbes and tried to elucidate the relationships between the gene-transferring microbes. A total of 13,514 high confidence HGT genes were identified in 308 human microbes. The horizontally transferred genes were enriched for Gene Ontology terms pertaining to catalytic functions and metabolic processes. Construction of an HGT event network suggested that the human microbes could be divided into specific communities which only partly overlap their distribution in human body. Our research suggests that human microbiome may facilitate frequent horizontal gene transfer among bacteria in human body. Awareness of HGT in human microbiome may aid our understanding of the relationship between the human microbiome and human health.}, }
@article {pmid22807668, year = {2012}, author = {Faust, K and Sathirapongsasuti, JF and Izard, J and Segata, N and Gevers, D and Raes, J and Huttenhower, C}, title = {Microbial co-occurrence relationships in the human microbiome.}, journal = {PLoS computational biology}, volume = {8}, number = {7}, pages = {e1002606}, pmid = {22807668}, issn = {1553-7358}, support = {U54HG004969/HG/NHGRI NIH HHS/United States ; P30 DK043351/DK/NIDDK NIH HHS/United States ; R01 HG005969/HG/NHGRI NIH HHS/United States ; U54 HG004969/HG/NHGRI NIH HHS/United States ; CA139193/CA/NCI NIH HHS/United States ; R21 CA139193/CA/NCI NIH HHS/United States ; 1R01HG005969/HG/NHGRI NIH HHS/United States ; }, mesh = {Bacteria/*classification ; *Bacterial Physiological Phenomena ; Computational Biology ; DNA, Bacterial/chemistry ; Ecosystem ; Female ; Gastrointestinal Tract/microbiology ; Genes, rRNA/genetics ; Humans ; Linear Models ; Male ; Metagenome/*physiology ; Microbial Interactions/physiology ; Nasal Cavity/microbiology ; Phylogeny ; Skin/microbiology ; Vagina/microbiology ; }, abstract = {The healthy microbiota show remarkable variability within and among individuals. In addition to external exposures, ecological relationships (both oppositional and symbiotic) between microbial inhabitants are important contributors to this variation. It is thus of interest to assess what relationships might exist among microbes and determine their underlying reasons. The initial Human Microbiome Project (HMP) cohort, comprising 239 individuals and 18 different microbial habitats, provides an unprecedented resource to detect, catalog, and analyze such relationships. Here, we applied an ensemble method based on multiple similarity measures in combination with generalized boosted linear models (GBLMs) to taxonomic marker (16S rRNA gene) profiles of this cohort, resulting in a global network of 3,005 significant co-occurrence and co-exclusion relationships between 197 clades occurring throughout the human microbiome. This network revealed strong niche specialization, with most microbial associations occurring within body sites and a number of accompanying inter-body site relationships. Microbial communities within the oropharynx grouped into three distinct habitats, which themselves showed no direct influence on the composition of the gut microbiota. Conversely, niches such as the vagina demonstrated little to no decomposition into region-specific interactions. Diverse mechanisms underlay individual interactions, with some such as the co-exclusion of Porphyromonaceae family members and Streptococcus in the subgingival plaque supported by known biochemical dependencies. These differences varied among broad phylogenetic groups as well, with the Bacilli and Fusobacteria, for example, both enriched for exclusion of taxa from other clades. Comparing phylogenetic versus functional similarities among bacteria, we show that dominant commensal taxa (such as Prevotellaceae and Bacteroides in the gut) often compete, while potential pathogens (e.g. Treponema and Prevotella in the dental plaque) are more likely to co-occur in complementary niches. This approach thus serves to open new opportunities for future targeted mechanistic studies of the microbial ecology of the human microbiome.}, }
@article {pmid22796884, year = {2012}, author = {Faust, K and Raes, J}, title = {Microbial interactions: from networks to models.}, journal = {Nature reviews. Microbiology}, volume = {10}, number = {8}, pages = {538-550}, pmid = {22796884}, issn = {1740-1534}, mesh = {*Biota ; Humans ; Metagenomics/*methods ; *Microbial Interactions ; }, abstract = {Metagenomics and 16S pyrosequencing have enabled the study of ecosystem structure and dynamics to great depth and accuracy. Co-occurrence and correlation patterns found in these data sets are increasingly used for the prediction of species interactions in environments ranging from the oceans to the human microbiome. In addition, parallelized co-culture assays and combinatorial labelling experiments allow high-throughput discovery of cooperative and competitive relationships between species. In this Review, we describe how these techniques are opening the way towards global ecosystem network prediction and the development of ecosystem-wide dynamic models.}, }
@article {pmid22794299, year = {2012}, author = {Stieglmeier, M and Rettberg, P and Barczyk, S and Bohmeier, M and Pukall, R and Wirth, R and Moissl-Eichinger, C}, title = {Abundance and diversity of microbial inhabitants in European spacecraft-associated clean rooms.}, journal = {Astrobiology}, volume = {12}, number = {6}, pages = {572-585}, doi = {10.1089/ast.2011.0735}, pmid = {22794299}, issn = {1557-8070}, mesh = {Bacteria/classification/*genetics/isolation &amp; purification ; Biodiversity ; Colony Count, Microbial ; *Environment, Controlled ; Environmental Microbiology ; *Equipment Contamination ; Europe ; Genes, rRNA ; Humans ; RNA, Ribosomal, 16S/analysis ; Real-Time Polymerase Chain Reaction/*methods ; Spacecraft/*standards ; }, abstract = {The determination of the microbial load of a spacecraft en route to interesting extraterrestrial environments is mandatory and currently based on the culturable, heat-shock-surviving portion of microbial contaminants. Our study compared these classical bioburden measurements as required by NASA's and ESA's guidelines for the microbial examination of flight hardware, with molecular analysis methods (16S rRNA gene cloning and quantitative PCR) to further develop our understanding of the diversity and abundance of the microbial communities of spacecraft-associated clean rooms. Three samplings of the Herschel Space Observatory and its surrounding clean rooms were performed in two different European facilities. Molecular analyses detected a broad diversity of microbes typically found in the human microbiome with three bacterial genera (Staphylococcus, Propionibacterium, and Brevundimonas) common to all three locations. Bioburden measurements revealed a low, but heterogeneous, abundance of spore-forming and other heat-resistant microorganisms. Total cell numbers estimated by quantitative real-time PCR were typically 3 orders of magnitude greater than those determined by viable counts, which indicates a tendency for traditional methods to underestimate the extent of clean room bioburden. Furthermore, the molecular methods allowed the detection of a much broader diversity than traditional culture-based methods.}, }
@article {pmid22792232, year = {2012}, author = {Markowitz, VM and Chen, IM and Chu, K and Szeto, E and Palaniappan, K and Jacob, B and Ratner, A and Liolios, K and Pagani, I and Huntemann, M and Mavromatis, K and Ivanova, NN and Kyrpides, NC}, title = {IMG/M-HMP: a metagenome comparative analysis system for the Human Microbiome Project.}, journal = {PloS one}, volume = {7}, number = {7}, pages = {e40151}, pmid = {22792232}, issn = {1932-6203}, support = {U01 HG004866/HG/NHGRI NIH HHS/United States ; U01-HG004866/HG/NHGRI NIH HHS/United States ; }, mesh = {Archaea/genetics ; Bacteria/genetics ; *Database Management Systems ; *Databases, Genetic ; Eukaryota/genetics ; Humans ; *Internet ; Metagenome/*genetics ; User-Computer Interface ; }, abstract = {The Integrated Microbial Genomes and Metagenomes (IMG/M) resource is a data management system that supports the analysis of sequence data from microbial communities in the integrated context of all publicly available draft and complete genomes from the three domains of life as well as a large number of plasmids and viruses. IMG/M currently contains thousands of genomes and metagenome samples with billions of genes. IMG/M-HMP is an IMG/M data mart serving the US National Institutes of Health (NIH) Human Microbiome Project (HMP), focussed on HMP generated metagenome datasets, and is one of the central resources provided from the HMP Data Analysis and Coordination Center (DACC). IMG/M-HMP is available at http://www.hmpdacc-resources.org/imgm_hmp/.}, }
@article {pmid22772032, year = {2012}, author = {Somberg, JC}, title = {The human microbiome and therapeutics.}, journal = {American journal of therapeutics}, volume = {19}, number = {4}, pages = {247}, doi = {10.1097/MJT.0b013e318265ed0f}, pmid = {22772032}, issn = {1536-3686}, mesh = {Drug Therapy ; Drug-Related Side Effects and Adverse Reactions ; Humans ; *Metagenome ; Pharmaceutical Preparations/administration &amp; dosage/*metabolism ; }, }
@article {pmid22763544, year = {2012}, author = {Chatterjee, B and Thakur, SS}, title = {Microbial profiling: extend ethnicity of human microbiome.}, journal = {Nature}, volume = {487}, number = {7405}, pages = {39}, pmid = {22763544}, issn = {1476-4687}, mesh = {Aging ; Cultural Diversity ; Environment ; Feeding Behavior ; Humans ; Life Style ; *Metagenome ; }, }
@article {pmid22759449, year = {2012}, author = {Dollive, S and Peterfreund, GL and Sherrill-Mix, S and Bittinger, K and Sinha, R and Hoffmann, C and Nabel, CS and Hill, DA and Artis, D and Bachman, MA and Custers-Allen, R and Grunberg, S and Wu, GD and Lewis, JD and Bushman, FD}, title = {A tool kit for quantifying eukaryotic rRNA gene sequences from human microbiome samples.}, journal = {Genome biology}, volume = {13}, number = {7}, pages = {R60}, pmid = {22759449}, issn = {1474-760X}, support = {T32-AI060516/AI/NIAID NIH HHS/United States ; UH2DK083981/DK/NIDDK NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; AI087990/AI/NIAID NIH HHS/United States ; T32 AI060516/AI/NIAID NIH HHS/United States ; AI083480/AI/NIAID NIH HHS/United States ; T32 AI055400/AI/NIAID NIH HHS/United States ; S10RR024525/RR/NCRR NIH HHS/United States ; UL1RR024134/RR/NCRR NIH HHS/United States ; AI39368/AI/NIAID NIH HHS/United States ; U01AI095608/AI/NIAID NIH HHS/United States ; K24-DK078228/DK/NIDDK NIH HHS/United States ; }, mesh = {Eukaryota/*classification/genetics/*isolation &amp; purification ; Feces/microbiology ; High-Throughput Nucleotide Sequencing ; Humans ; *Microbiota ; RNA/genetics ; RNA, Ribosomal, 18S/*genetics ; Sequence Analysis, RNA/*methods ; Single-Cell Analysis/methods ; Software ; }, abstract = {Eukaryotic microorganisms are important but understudied components of the human microbiome. Here we present a pipeline for analysis of deep sequencing data on single cell eukaryotes. We designed a new 18S rRNA gene-specific PCR primer set and compared a published rRNA gene internal transcribed spacer (ITS) gene primer set. Amplicons were tested against 24 specimens from defined eukaryotes and eight well-characterized human stool samples. A software pipeline https://sourceforge.net/projects/brocc/ was developed for taxonomic attribution, validated against simulated data, and tested on pyrosequence data. This study provides a well-characterized tool kit for sequence-based enumeration of eukaryotic organisms in human microbiome samples.}, }
@article {pmid22754581, year = {2011}, author = {Ma, ZS and Abdo, Z and Forney, LJ}, title = {Caring about trees in the forest: incorporating frailty in risk analysis for personalized medicine.}, journal = {Personalized medicine}, volume = {8}, number = {6}, pages = {681-688}, pmid = {22754581}, issn = {1741-0541}, support = {U19 AI084044/AI/NIAID NIH HHS/United States ; U19 AI084044-03/AI/NIAID NIH HHS/United States ; UH2 AI083264/AI/NIAID NIH HHS/United States ; UH2 AI083264-01/AI/NIAID NIH HHS/United States ; }, abstract = {The analysis of frailty originated in studies of aging and demography in which the objective was to demonstrate that the hazard rates (mortality risks) of individuals in a population could significantly differ from the population hazard rate as a whole. The differences between these two hazard rates can arise from frailty - differences among individuals that are not observed in a study. We posit that frailty modeling is a useful approach for risk analysis in personalized medicine because it provides a way to address the important and perplexing question of how to translate findings from population studies to the diagnosis and treatment of disease in specific individuals. Our suggestion is based on three unique advantages of frailty modeling: frailty modeling offers an effective approach to analyze the risks at both the individual and population levels and can be used to infer relationships between the two; frailty modeling can be used to analyze the dependence between survival events - one of the most difficult issues in any field that involves common risks; and frailty modeling can be used to describe unobserved or unobservable risks. Finally, we suggest that frailty modeling should be particularly useful in the study and treatment of diseases that are caused or influenced by the human microbiome. By doing so, truly 'personalized' medicine can advance based on a better understanding of the risks to both 'trees' (individuals) and 'forests' (populations).}, }
@article {pmid22722865, year = {2012}, author = {Devkota, S and Wang, Y and Musch, MW and Leone, V and Fehlner-Peach, H and Nadimpalli, A and Antonopoulos, DA and Jabri, B and Chang, EB}, title = {Dietary-fat-induced taurocholic acid promotes pathobiont expansion and colitis in Il10-/- mice.}, journal = {Nature}, volume = {487}, number = {7405}, pages = {104-108}, pmid = {22722865}, issn = {1476-4687}, support = {DK-42086/DK/NIDDK NIH HHS/United States ; UH3 DK083993/DK/NIDDK NIH HHS/United States ; T32 DK007074/DK/NIDDK NIH HHS/United States ; UH3DK083993/DK/NIDDK NIH HHS/United States ; DK47722/DK/NIDDK NIH HHS/United States ; R01 DK097268/DK/NIDDK NIH HHS/United States ; R01 DK047722/DK/NIDDK NIH HHS/United States ; F31AT006073/AT/NCCIH NIH HHS/United States ; P30 DK042086/DK/NIDDK NIH HHS/United States ; F31 AT006073/AT/NCCIH NIH HHS/United States ; R37 DK047722/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Bile Acids and Salts/metabolism ; Bilophila/*drug effects/growth &amp; development ; Colitis/*chemically induced/immunology/*microbiology/pathology ; Diet, Fat-Restricted ; Dietary Fats/*pharmacology ; Inflammation/chemically induced/immunology/microbiology ; Inflammatory Bowel Diseases/chemically induced/microbiology/pathology ; Interleukin-10/*deficiency/genetics ; Metagenome/*drug effects ; Mice ; Mice, Inbred C57BL ; Milk/chemistry ; Molecular Sequence Data ; Safflower Oil/pharmacology ; Sulfites/metabolism ; Taurine/metabolism ; Taurocholic Acid/*metabolism/pharmacology ; Th1 Cells/drug effects/immunology ; }, abstract = {The composite human microbiome of Western populations has probably changed over the past century, brought on by new environmental triggers that often have a negative impact on human health. Here we show that consumption of a diet high in saturated (milk-derived) fat, but not polyunsaturated (safflower oil) fat, changes the conditions for microbial assemblage and promotes the expansion of a low-abundance, sulphite-reducing pathobiont, Bilophila wadsworthia. This was associated with a pro-inflammatory T helper type 1 (T(H)1) immune response and increased incidence of colitis in genetically susceptible Il10(−/−), but not wild-type mice. These effects are mediated by milk-derived-fat-promoted taurine conjugation of hepatic bile acids, which increases the availability of organic sulphur used by sulphite-reducing microorganisms like B. wadsworthia. When mice were fed a low-fat diet supplemented with taurocholic acid, but not with glycocholic acid, for example, a bloom of B. wadsworthia and development of colitis were observed in Il10(−/−) mice. Together these data show that dietary fats, by promoting changes in host bile acid composition, can markedly alter conditions for gut microbial assemblage, resulting in dysbiosis that can perturb immune homeostasis. The data provide a plausible mechanistic basis by which Western-type diets high in certain saturated fats might increase the prevalence of complex immune-mediated diseases like inflammatory bowel disease in genetically susceptible hosts.}, }
@article {pmid22720093, year = {2012}, author = {, }, title = {Evaluation of 16S rDNA-based community profiling for human microbiome research.}, journal = {PloS one}, volume = {7}, number = {6}, pages = {e39315}, pmid = {22720093}, issn = {1932-6203}, support = {U54 HG004973/HG/NHGRI NIH HHS/United States ; U54HG004969/HG/NHGRI NIH HHS/United States ; HHSN272200900018C/AI/NIAID NIH HHS/United States ; HHSN272200900008C/AI/NIAID NIH HHS/United States ; U54 HG004968/HG/NHGRI NIH HHS/United States ; U54HG004973/HG/NHGRI NIH HHS/United States ; U54HG003079/HG/NHGRI NIH HHS/United States ; HHSN2722009000018C//PHS HHS/United States ; U54 HG003079/HG/NHGRI NIH HHS/United States ; U54 HG004969/HG/NHGRI NIH HHS/United States ; U54HG004968/HG/NHGRI NIH HHS/United States ; HHSN272200900001C/AI/NIAID NIH HHS/United States ; U54 AI084844/AI/NIAID NIH HHS/United States ; 1U01HG004866/HG/NHGRI NIH HHS/United States ; U54 HG003273/HG/NHGRI NIH HHS/United States ; U01 HG004866/HG/NHGRI NIH HHS/United States ; U54AI084844/AI/NIAID NIH HHS/United States ; }, mesh = {Bacteria/classification/genetics ; Bayes Theorem ; Humans ; *Metagenome ; RNA, Ribosomal, 16S/*genetics ; }, abstract = {The Human Microbiome Project will establish a reference data set for analysis of the microbiome of healthy adults by surveying multiple body sites from 300 people and generating data from over 12,000 samples. To characterize these samples, the participating sequencing centers evaluated and adopted 16S rDNA community profiling protocols for ABI 3730 and 454 FLX Titanium sequencing. In the course of establishing protocols, we examined the performance and error characteristics of each technology, and the relationship of sequence error to the utility of 16S rDNA regions for classification- and OTU-based analysis of community structure. The data production protocols used for this work are those used by the participating centers to produce 16S rDNA sequence for the Human Microbiome Project. Thus, these results can be informative for interpreting the large body of clinical 16S rDNA data produced for this project.}, }
@article {pmid22719832, year = {2012}, author = {Aagaard, K and Riehle, K and Ma, J and Segata, N and Mistretta, TA and Coarfa, C and Raza, S and Rosenbaum, S and Van den Veyver, I and Milosavljevic, A and Gevers, D and Huttenhower, C and Petrosino, J and Versalovic, J}, title = {A metagenomic approach to characterization of the vaginal microbiome signature in pregnancy.}, journal = {PloS one}, volume = {7}, number = {6}, pages = {e36466}, pmid = {22719832}, issn = {1932-6203}, support = {DP2120OD001500-01/OD/NIH HHS/United States ; #R01DK080558-01/DK/NIDDK NIH HHS/United States ; UH3 DK083990/DK/NIDDK NIH HHS/United States ; NIHU54HG004969/HG/NHGRI NIH HHS/United States ; R01 DK080558/DK/NIDDK NIH HHS/United States ; DP2 OD001500/OD/NIH HHS/United States ; R01 HG005969/HG/NHGRI NIH HHS/United States ; U54 HG004969/HG/NHGRI NIH HHS/United States ; UH3 DK083990L/DK/NIDDK NIH HHS/United States ; NIH 1R01HG005969/HG/NHGRI NIH HHS/United States ; }, mesh = {Adult ; Bacteria/classification/genetics/isolation &amp; purification ; DNA, Bacterial/genetics ; Female ; Humans ; *Metagenome ; *Metagenomics ; Pregnancy ; Vagina/*microbiology ; }, abstract = {While current major national research efforts (i.e., the NIH Human Microbiome Project) will enable comprehensive metagenomic characterization of the adult human microbiota, how and when these diverse microbial communities take up residence in the host and during reproductive life are unexplored at a population level. Because microbial abundance and diversity might differ in pregnancy, we sought to generate comparative metagenomic signatures across gestational age strata. DNA was isolated from the vagina (introitus, posterior fornix, midvagina) and the V5V3 region of bacterial 16S rRNA genes were sequenced (454FLX Titanium platform). Sixty-eight samples from 24 healthy gravidae (18 to 40 confirmed weeks) were compared with 301 non-pregnant controls (60 subjects). Generated sequence data were quality filtered, taxonomically binned, normalized, and organized by phylogeny and into operational taxonomic units (OTU); principal coordinates analysis (PCoA) of the resultant beta diversity measures were used for visualization and analysis in association with sample clinical metadata. Altogether, 1.4 gigabytes of data containing >2.5 million reads (averaging 6,837 sequences/sample of 493 nt in length) were generated for computational analyses. Although gravidae were not excluded by virtue of a posterior fornix pH >4.5 at the time of screening, unique vaginal microbiome signature encompassing several specific OTUs and higher-level clades was nevertheless observed and confirmed using a combination of phylogenetic, non-phylogenetic, supervised, and unsupervised approaches. Both overall diversity and richness were reduced in pregnancy, with dominance of Lactobacillus species (L. iners crispatus, jensenii and johnsonii, and the orders Lactobacillales (and Lactobacillaceae family), Clostridiales, Bacteroidales, and Actinomycetales. This intergroup comparison using rigorous standardized sampling protocols and analytical methodologies provides robust initial evidence that the vaginal microbial 16S rRNA gene catalogue uniquely differs in pregnancy, with variance of taxa across vaginal subsite and gestational age.}, }
@article {pmid22719831, year = {2012}, author = {Martin, J and Sykes, S and Young, S and Kota, K and Sanka, R and Sheth, N and Orvis, J and Sodergren, E and Wang, Z and Weinstock, GM and Mitreva, M}, title = {Optimizing read mapping to reference genomes to determine composition and species prevalence in microbial communities.}, journal = {PloS one}, volume = {7}, number = {6}, pages = {e36427}, pmid = {22719831}, issn = {1932-6203}, support = {U54HG004969/HG/NHGRI NIH HHS/United States ; NIH-NHGRI U54HG003079//PHS HHS/United States ; U54 AI084844/AI/NIAID NIH HHS/United States ; U54AI084844/AI/NIAID NIH HHS/United States ; U54 HG004968/HG/NHGRI NIH HHS/United States ; U54 HG003079/HG/NHGRI NIH HHS/United States ; U54 HG004969/HG/NHGRI NIH HHS/United States ; UH3 AI083263/AI/NIAID NIH HHS/United States ; U54HG004968/HG/NHGRI NIH HHS/United States ; NIH-NIAID UH3AI083263//PHS HHS/United States ; }, mesh = {Biodiversity ; Databases, Factual ; Humans ; *Metagenome ; *Metagenomics ; Phylogeny ; }, abstract = {The Human Microbiome Project (HMP) aims to characterize the microbial communities of 18 body sites from healthy individuals. To accomplish this, the HMP generated two types of shotgun data: reference shotgun sequences isolated from different anatomical sites on the human body and shotgun metagenomic sequences from the microbial communities of each site. The alignment strategy for characterizing these metagenomic communities using available reference sequence is important to the success of HMP data analysis. Six next-generation aligners were used to align a community of known composition against a database comprising reference organisms known to be present in that community. All aligners report nearly complete genome coverage (>97%) for strains with over 6X depth of coverage, however they differ in speed, memory requirement and ease of use issues such as database size limitations and supported mapping strategies. The selected aligner was tested across a range of parameters to maximize sensitivity while maintaining a low false positive rate. We found that constraining alignment length had more impact on sensitivity than does constraining similarity in all cases tested. However, when reference species were replaced with phylogenetic neighbors, similarity begins to play a larger role in detection. We also show that choosing the top hit randomly when multiple, equally strong mappings are available increases overall sensitivity at the expense of taxonomic resolution. The results of this study identified a strategy that was used to map over 3 tera-bases of microbial sequence against a database of more than 5,000 reference genomes in just over a month.}, }
@article {pmid22719826, year = {2012}, author = {Wylie, KM and Truty, RM and Sharpton, TJ and Mihindukulasuriya, KA and Zhou, Y and Gao, H and Sodergren, E and Weinstock, GM and Pollard, KS}, title = {Novel bacterial taxa in the human microbiome.}, journal = {PloS one}, volume = {7}, number = {6}, pages = {e35294}, pmid = {22719826}, issn = {1932-6203}, support = {U54 HG004968/HG/NHGRI NIH HHS/United States ; U54HG004968/HG/NHGRI NIH HHS/United States ; }, mesh = {DNA, Ribosomal/genetics ; Humans ; *Metagenome ; Metagenomics ; }, abstract = {The human gut harbors thousands of bacterial taxa. A profusion of metagenomic sequence data has been generated from human stool samples in the last few years, raising the question of whether more taxa remain to be identified. We assessed metagenomic data generated by the Human Microbiome Project Consortium to determine if novel taxa remain to be discovered in stool samples from healthy individuals. To do this, we established a rigorous bioinformatics pipeline that uses sequence data from multiple platforms (Illumina GAIIX and Roche 454 FLX Titanium) and approaches (whole-genome shotgun and 16S rDNA amplicons) to validate novel taxa. We applied this approach to stool samples from 11 healthy subjects collected as part of the Human Microbiome Project. We discovered several low-abundance, novel bacterial taxa, which span three major phyla in the bacterial tree of life. We determined that these taxa are present in a larger set of Human Microbiome Project subjects and are found in two sampling sites (Houston and St. Louis). We show that the number of false-positive novel sequences (primarily chimeric sequences) would have been two orders of magnitude higher than the true number of novel taxa without validation using multiple datasets, highlighting the importance of establishing rigorous standards for the identification of novel taxa in metagenomic data. The majority of novel sequences are related to the recently discovered genus Barnesiella, further encouraging efforts to characterize the members of this genus and to study their roles in the microbial communities of the gut. A better understanding of the effects of less-abundant bacteria is important as we seek to understand the complex gut microbiome in healthy individuals and link changes in the microbiome to disease.}, }
@article {pmid22719824, year = {2012}, author = {Huse, SM and Ye, Y and Zhou, Y and Fodor, AA}, title = {A core human microbiome as viewed through 16S rRNA sequence clusters.}, journal = {PloS one}, volume = {7}, number = {6}, pages = {e34242}, pmid = {22719824}, issn = {1932-6203}, support = {NIH-NHGRI U54HG004968//PHS HHS/United States ; U54 HG004968/HG/NHGRI NIH HHS/United States ; UH2 DK083993/DK/NIDDK NIH HHS/United States ; 1UH2DK083993-01/DK/NIDDK NIH HHS/United States ; R01 HG004908/HG/NHGRI NIH HHS/United States ; NIH 1R01HG004908/HG/NHGRI NIH HHS/United States ; }, mesh = {Humans ; *Metagenome ; RNA, Ribosomal, 16S/*genetics ; Reference Values ; }, abstract = {We explore the microbiota of 18 body sites in over 200 individuals using sequences amplified V1-V3 and the V3-V5 small subunit ribosomal RNA (16S) hypervariable regions as part of the NIH Common Fund Human Microbiome Project. The body sites with the greatest number of core OTUs, defined as OTUs shared amongst 95% or more of the individuals, were the oral sites (saliva, tongue, cheek, gums, and throat) followed by the nose, stool, and skin, while the vaginal sites had the fewest number of OTUs shared across subjects. We found that commonalities between samples based on taxonomy could sometimes belie variability at the sub-genus OTU level. This was particularly apparent in the mouth where a given genus can be present in many different oral sites, but the sub-genus OTUs show very distinct site selection, and in the vaginal sites, which are consistently dominated by the Lactobacillus genus but have distinctly different sub-genus V1-V3 OTU populations across subjects. Different body sites show approximately a ten-fold difference in estimated microbial richness, with stool samples having the highest estimated richness, followed by the mouth, throat and gums, then by the skin, nasal and vaginal sites. Richness as measured by the V1-V3 primers was consistently higher than richness measured by V3-V5. We also show that when such a large cohort is analyzed at the genus level, most subjects fit the stool "enterotype" profile, but other subjects are intermediate, blurring the distinction between the enterotypes. When analyzed at the finer-scale, OTU level, there was little or no segregation into stool enterotypes, but in the vagina distinct biotypes were apparent. Finally, we note that even OTUs present in nearly every subject, or that dominate in some samples, showed orders of magnitude variation in relative abundance emphasizing the highly variable nature across individuals.}, }
@article {pmid22719823, year = {2012}, author = {Li, K and Bihan, M and Yooseph, S and Methé, BA}, title = {Analyses of the microbial diversity across the human microbiome.}, journal = {PloS one}, volume = {7}, number = {6}, pages = {e32118}, pmid = {22719823}, issn = {1932-6203}, support = {U54 AI084844/AI/NIAID NIH HHS/United States ; #AI084844/AI/NIAID NIH HHS/United States ; }, mesh = {Biodiversity ; Humans ; *Metagenome ; }, abstract = {Analysis of human body microbial diversity is fundamental to understanding community structure, biology and ecology. The National Institutes of Health Human Microbiome Project (HMP) has provided an unprecedented opportunity to examine microbial diversity within and across body habitats and individuals through pyrosequencing-based profiling of 16 S rRNA gene sequences (16 S) from habits of the oral, skin, distal gut, and vaginal body regions from over 200 healthy individuals enabling the application of statistical techniques. In this study, two approaches were applied to elucidate the nature and extent of human microbiome diversity. First, bootstrap and parametric curve fitting techniques were evaluated to estimate the maximum number of unique taxa, S(max), and taxa discovery rate for habitats across individuals. Next, our results demonstrated that the variation of diversity within low abundant taxa across habitats and individuals was not sufficiently quantified with standard ecological diversity indices. This impact from low abundant taxa motivated us to introduce a novel rank-based diversity measure, the Tail statistic, ("τ"), based on the standard deviation of the rank abundance curve if made symmetric by reflection around the most abundant taxon. Due to τ's greater sensitivity to low abundant taxa, its application to diversity estimation of taxonomic units using taxonomic dependent and independent methods revealed a greater range of values recovered between individuals versus body habitats, and different patterns of diversity within habitats. The greatest range of τ values within and across individuals was found in stool, which also exhibited the most undiscovered taxa. Oral and skin habitats revealed variable diversity patterns, while vaginal habitats were consistently the least diverse. Collectively, these results demonstrate the importance, and motivate the introduction, of several visualization and analysis methods tuned specifically for next-generation sequence data, further revealing that low abundant taxa serve as an important reservoir of genetic diversity in the human microbiome.}, }
@article {pmid22719821, year = {2012}, author = {Goll, J and Thiagarajan, M and Abubucker, S and Huttenhower, C and Yooseph, S and Methé, BA}, title = {A case study for large-scale human microbiome analysis using JCVI's metagenomics reports (METAREP).}, journal = {PloS one}, volume = {7}, number = {6}, pages = {e29044}, pmid = {22719821}, issn = {1932-6203}, support = {U54 AI084844/AI/NIAID NIH HHS/United States ; U54 HG004968/HG/NHGRI NIH HHS/United States ; N01 AI 30071/AI/NIAID NIH HHS/United States ; R01 HG005969/HG/NHGRI NIH HHS/United States ; U54HG004968/HG/NHGRI NIH HHS/United States ; N01 AI030071/AI/NIAID NIH HHS/United States ; U54-AI084844/AI/NIAID NIH HHS/United States ; 1R01HG005969/HG/NHGRI NIH HHS/United States ; }, mesh = {Bacteria/*classification/genetics ; Cluster Analysis ; Humans ; *Metagenomics ; National Institutes of Health (U.S.) ; United States ; }, abstract = {As metagenomic studies continue to increase in their number, sequence volume and complexity, the scalability of biological analysis frameworks has become a rate-limiting factor to meaningful data interpretation. To address this issue, we have developed JCVI Metagenomics Reports (METAREP) as an open source tool to query, browse, and compare extremely large volumes of metagenomic annotations. Here we present improvements to this software including the implementation of a dynamic weighting of taxonomic and functional annotation, support for distributed searches, advanced clustering routines, and integration of additional annotation input formats. The utility of these improvements to data interpretation are demonstrated through the application of multiple comparative analysis strategies to shotgun metagenomic data produced by the National Institutes of Health Roadmap for Biomedical Research Human Microbiome Project (HMP) (http://nihroadmap.nih.gov). Specifically, the scalability of the dynamic weighting feature is evaluated and established by its application to the analysis of over 400 million weighted gene annotations derived from 14 billion short reads as predicted by the HMP Unified Metabolic Analysis Network (HUMAnN) pipeline. Further, the capacity of METAREP to facilitate the identification and simultaneous comparison of taxonomic and functional annotations including biological pathway and individual enzyme abundances from hundreds of community samples is demonstrated by providing scenarios that describe how these data can be mined to answer biological questions related to the human microbiome. These strategies provide users with a reference of how to conduct similar large-scale metagenomic analyses using METAREP with their own sequence data, while in this study they reveal insights into the nature and extent of variation in taxonomic and functional profiles across body habitats and individuals. Over one thousand HMP WGS datasets and the latest open source code are available at http://www.jcvi.org/hmp-metarep.}, }
@article {pmid22719820, year = {2012}, author = {Cantarel, BL and Lombard, V and Henrissat, B}, title = {Complex carbohydrate utilization by the healthy human microbiome.}, journal = {PloS one}, volume = {7}, number = {6}, pages = {e28742}, pmid = {22719820}, issn = {1932-6203}, support = {U01 HG004866/HG/NHGRI NIH HHS/United States ; 1U01HG004866-01/HG/NHGRI NIH HHS/United States ; }, mesh = {*Carbohydrate Metabolism ; Humans ; *Metagenome ; Reference Values ; }, abstract = {The various ecological habitats in the human body provide microbes a wide array of nutrient sources and survival challenges. Advances in technology such as DNA sequencing have allowed a deeper perspective into the molecular function of the human microbiota than has been achievable in the past. Here we aimed to examine the enzymes that cleave complex carbohydrates (CAZymes) in the human microbiome in order to determine (i) whether the CAZyme profiles of bacterial genomes are more similar within body sites or bacterial families and (ii) the sugar degradation and utilization capabilities of microbial communities inhabiting various human habitats. Upon examination of 493 bacterial references genomes from 12 human habitats, we found that sugar degradation capabilities of taxa are more similar to others in the same bacterial family than to those inhabiting the same habitat. Yet, the analysis of 520 metagenomic samples from five major body sites show that even when the community composition varies the CAZyme profiles are very similar within a body site, suggesting that the observed functional profile and microbial habitation have adapted to the local carbohydrate composition. When broad sugar utilization was compared within the five major body sites, the gastrointestinal track contained the highest potential for total sugar degradation, while dextran and peptidoglycan degradation were highest in oral and vaginal sites respectively. Our analysis suggests that the carbohydrate composition of each body site has a profound influence and probably constitutes one of the major driving forces that shapes the community composition and therefore the CAZyme profile of the local microbial communities, which in turn reflects the microbiome fitness to a body site.}, }
@article {pmid22719260, year = {2012}, author = {Rho, M and Wu, YW and Tang, H and Doak, TG and Ye, Y}, title = {Diverse CRISPRs evolving in human microbiomes.}, journal = {PLoS genetics}, volume = {8}, number = {6}, pages = {e1002441}, pmid = {22719260}, issn = {1553-7404}, support = {R01 HG004908/HG/NHGRI NIH HHS/United States ; 1R01HG004908/HG/NHGRI NIH HHS/United States ; }, mesh = {Archaea/genetics ; Bacteria/genetics/virology ; Bacteriophages/genetics ; Base Sequence ; DNA, Intergenic/*genetics ; *Evolution, Molecular ; Genome, Bacterial ; Humans ; Inverted Repeat Sequences/*genetics ; Metagenome/*genetics ; Metagenomics ; Molecular Sequence Data ; Plasmids/genetics ; Sequence Analysis, DNA ; Streptococcus/genetics/virology ; }, abstract = {CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) loci, together with cas (CRISPR-associated) genes, form the CRISPR/Cas adaptive immune system, a primary defense strategy that eubacteria and archaea mobilize against foreign nucleic acids, including phages and conjugative plasmids. Short spacer sequences separated by the repeats are derived from foreign DNA and direct interference to future infections. The availability of hundreds of shotgun metagenomic datasets from the Human Microbiome Project (HMP) enables us to explore the distribution and diversity of known CRISPRs in human-associated microbial communities and to discover new CRISPRs. We propose a targeted assembly strategy to reconstruct CRISPR arrays, which whole-metagenome assemblies fail to identify. For each known CRISPR type (identified from reference genomes), we use its direct repeat consensus sequence to recruit reads from each HMP dataset and then assemble the recruited reads into CRISPR loci; the unique spacer sequences can then be extracted for analysis. We also identified novel CRISPRs or new CRISPR variants in contigs from whole-metagenome assemblies and used targeted assembly to more comprehensively identify these CRISPRs across samples. We observed that the distributions of CRISPRs (including 64 known and 86 novel ones) are largely body-site specific. We provide detailed analysis of several CRISPR loci, including novel CRISPRs. For example, known streptococcal CRISPRs were identified in most oral microbiomes, totaling ∼8,000 unique spacers: samples resampled from the same individual and oral site shared the most spacers; different oral sites from the same individual shared significantly fewer, while different individuals had almost no common spacers, indicating the impact of subtle niche differences on the evolution of CRISPR defenses. We further demonstrate potential applications of CRISPRs to the tracing of rare species and the virus exposure of individuals. This work indicates the importance of effective identification and characterization of CRISPR loci to the study of the dynamic ecology of microbiomes.}, }
@article {pmid22719234, year = {2012}, author = {Abubucker, S and Segata, N and Goll, J and Schubert, AM and Izard, J and Cantarel, BL and Rodriguez-Mueller, B and Zucker, J and Thiagarajan, M and Henrissat, B and White, O and Kelley, ST and Methé, B and Schloss, PD and Gevers, D and Mitreva, M and Huttenhower, C}, title = {Metabolic reconstruction for metagenomic data and its application to the human microbiome.}, journal = {PLoS computational biology}, volume = {8}, number = {6}, pages = {e1002358}, pmid = {22719234}, issn = {1553-7358}, support = {R01 HG005969/HG/NHGRI NIH HHS/United States ; R21 DE017106/DE/NIDCR NIH HHS/United States ; CA139193/CA/NCI NIH HHS/United States ; U54HG004968/HG/NHGRI NIH HHS/United States ; 5R01HG005975/HG/NHGRI NIH HHS/United States ; U54HG004969/HG/NHGRI NIH HHS/United States ; T32 AI007528/AI/NIAID NIH HHS/United States ; R01 HG005975/HG/NHGRI NIH HHS/United States ; U54 HG004968/HG/NHGRI NIH HHS/United States ; R21 CA139193/CA/NCI NIH HHS/United States ; 1R01HG005969/HG/NHGRI NIH HHS/United States ; DE017106/DE/NIDCR NIH HHS/United States ; U54 HG004969/HG/NHGRI NIH HHS/United States ; }, mesh = {Computational Biology ; Digestive System/metabolism/microbiology ; Female ; Genetics, Microbial ; Glycosaminoglycans/metabolism ; Humans ; Hydrogen-Ion Concentration ; Metabolic Networks and Pathways/genetics ; Metabolome/genetics ; *Metagenome ; Multigene Family ; Vagina/metabolism/microbiology ; }, abstract = {Microbial communities carry out the majority of the biochemical activity on the planet, and they play integral roles in processes including metabolism and immune homeostasis in the human microbiome. Shotgun sequencing of such communities' metagenomes provides information complementary to organismal abundances from taxonomic markers, but the resulting data typically comprise short reads from hundreds of different organisms and are at best challenging to assemble comparably to single-organism genomes. Here, we describe an alternative approach to infer the functional and metabolic potential of a microbial community metagenome. We determined the gene families and pathways present or absent within a community, as well as their relative abundances, directly from short sequence reads. We validated this methodology using a collection of synthetic metagenomes, recovering the presence and abundance both of large pathways and of small functional modules with high accuracy. We subsequently applied this method, HUMAnN, to the microbial communities of 649 metagenomes drawn from seven primary body sites on 102 individuals as part of the Human Microbiome Project (HMP). This provided a means to compare functional diversity and organismal ecology in the human microbiome, and we determined a core of 24 ubiquitously present modules. Core pathways were often implemented by different enzyme families within different body sites, and 168 functional modules and 196 metabolic pathways varied in metagenomic abundance specifically to one or more niches within the microbiome. These included glycosaminoglycan degradation in the gut, as well as phosphate and amino acid transport linked to host phenotype (vaginal pH) in the posterior fornix. An implementation of our methodology is available at http://huttenhower.sph.harvard.edu/humann. This provides a means to accurately and efficiently characterize microbial metabolic pathways and functional modules directly from high-throughput sequencing reads, enabling the determination of community roles in the HMP cohort and in future metagenomic studies.}, }
@article {pmid22711789, year = {2012}, author = {Chen, J and Bittinger, K and Charlson, ES and Hoffmann, C and Lewis, J and Wu, GD and Collman, RG and Bushman, FD and Li, H}, title = {Associating microbiome composition with environmental covariates using generalized UniFrac distances.}, journal = {Bioinformatics (Oxford, England)}, volume = {28}, number = {16}, pages = {2106-2113}, pmid = {22711789}, issn = {1367-4811}, support = {UH3 DK083981/DK/NIDDK NIH HHS/United States ; DK083981/DK/NIDDK NIH HHS/United States ; P30 AI045008/AI/NIAID NIH HHS/United States ; U01HL098957/HL/NHLBI NIH HHS/United States ; U01 HL098957/HL/NHLBI NIH HHS/United States ; R01 CA127334/CA/NCI NIH HHS/United States ; R01CA127334/CA/NCI NIH HHS/United States ; UH2 DK083981/DK/NIDDK NIH HHS/United States ; }, mesh = {Bacteria/genetics ; Cluster Analysis ; Computational Biology/*methods ; Computer Simulation ; Cross-Sectional Studies ; Diet ; Environment ; Humans ; Metagenome/*genetics ; *Models, Statistical ; Monte Carlo Method ; Smoking ; }, abstract = {MOTIVATION: The human microbiome plays an important role in human disease and health. Identification of factors that affect the microbiome composition can provide insights into disease mechanism as well as suggest ways to modulate the microbiome composition for therapeutical purposes. Distance-based statistical tests have been applied to test the association of microbiome composition with environmental or biological covariates. The unweighted and weighted UniFrac distances are the most widely used distance measures. However, these two measures assign too much weight either to rare lineages or to most abundant lineages, which can lead to loss of power when the important composition change occurs in moderately abundant lineages.<br><br>RESULTS: We develop generalized UniFrac distances that extend the weighted and unweighted UniFrac distances for detecting a much wider range of biologically relevant changes. We evaluate the use of generalized UniFrac distances in associating microbiome composition with environmental covariates using extensive Monte Carlo simulations. Our results show that tests using the unweighted and weighted UniFrac distances are less powerful in detecting abundance change in moderately abundant lineages. In contrast, the generalized UniFrac distance is most powerful in detecting such changes, yet it retains nearly all its power for detecting rare and highly abundant lineages. The generalized UniFrac distance also has an overall better power than the joint use of unweighted/weighted UniFrac distances. Application to two real microbiome datasets has demonstrated gains in power in testing the associations between human microbiome and diet intakes and habitual smoking.<br><br>AVAILABILITY: http://cran.r-project.org/web/packages/GUniFrac}, }
@article {pmid22703178, year = {2012}, author = {Grice, EA and Segre, JA}, title = {The human microbiome: our second genome.}, journal = {Annual review of genomics and human genetics}, volume = {13}, number = {}, pages = {151-170}, pmid = {22703178}, issn = {1545-293X}, support = {ZIA HG000180/ImNIH/Intramural NIH HHS/United States ; ZIA HG000180-11/ImNIH/Intramural NIH HHS/United States ; ZIA HG000180-12/ImNIH/Intramural NIH HHS/United States ; }, mesh = {Animals ; Bacteria/drug effects/genetics ; Drug Resistance, Bacterial ; Gastrointestinal Tract/microbiology ; Humans ; *Metagenome ; Molecular Typing ; Mouth/microbiology ; Sequence Analysis, DNA ; Skin/microbiology ; Urogenital System/microbiology ; }, abstract = {The human genome has been referred to as the blueprint of human biology. In this review we consider an essential but largely ignored overlay to that blueprint, the human microbiome, which is composed of those microbes that live in and on our bodies. The human microbiome is a source of genetic diversity, a modifier of disease, an essential component of immunity, and a functional entity that influences metabolism and modulates drug interactions. Characterization and analysis of the human microbiome have been greatly catalyzed by advances in genomic technologies. We discuss how these technologies have shaped this emerging field of study and advanced our understanding of the human microbiome. We also identify future challenges, many of which are common to human genetic studies, and predict that in the future, analyzing genetic variation and risk of human disease will sometimes necessitate the integration of human and microbial genomic data sets.}, }
@article {pmid22699610, year = {2012}, author = {, }, title = {A framework for human microbiome research.}, journal = {Nature}, volume = {486}, number = {7402}, pages = {215-221}, pmid = {22699610}, issn = {1476-4687}, support = {R01HG004856/HG/NHGRI NIH HHS/United States ; R01HG004908/HG/NHGRI NIH HHS/United States ; P30DE020751/DE/NIDCR NIH HHS/United States ; R21HG005811/HG/NHGRI NIH HHS/United States ; R01HG005172/HG/NHGRI NIH HHS/United States ; UH3DK083993/DK/NIDDK NIH HHS/United States ; R01 HG005969/HG/NHGRI NIH HHS/United States ; R01HG004900/HG/NHGRI NIH HHS/United States ; UH2 DK083990/DK/NIDDK NIH HHS/United States ; N01HG62088/HG/NHGRI NIH HHS/United States ; R01 HG004857/HG/NHGRI NIH HHS/United States ; U54 HG004973/HG/NHGRI NIH HHS/United States ; U01DE016937/DE/NIDCR NIH HHS/United States ; RC1DE020298/DE/NIDCR NIH HHS/United States ; UH2 AR057504/AR/NIAMS NIH HHS/United States ; U54HG004969/HG/NHGRI NIH HHS/United States ; T32 AI007528/AI/NIAID NIH HHS/United States ; U54 HG003067/HG/NHGRI NIH HHS/United States ; U54HG003273/HG/NHGRI NIH HHS/United States ; R01HG004877/HG/NHGRI NIH HHS/United States ; R01 HG004900/HG/NHGRI NIH HHS/United States ; DP2OD001500/OD/NIH HHS/United States ; R01HG004885/HG/NHGRI NIH HHS/United States ; R01HG004872/HG/NHGRI NIH HHS/United States ; R01 HG004856/HG/NHGRI NIH HHS/United States ; R01 HG005171/HG/NHGRI NIH HHS/United States ; UH3AI083263/AI/NIAID NIH HHS/United States ; UH2 AR057506/AR/NIAMS NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; UH2AR057504/AR/NIAMS NIH HHS/United States ; U01HG004866/HG/NHGRI NIH HHS/United States ; U54HG003067/HG/NHGRI NIH HHS/United States ; U54 AI084844/AI/NIAID NIH HHS/United States ; UH3AR057504/AR/NIAMS NIH HHS/United States ; U54 HG003273/HG/NHGRI NIH HHS/United States ; UH2AI083263/AI/NIAID NIH HHS/United States ; U01 HG004866/HG/NHGRI NIH HHS/United States ; U54AI084844/AI/NIAID NIH HHS/United States ; R01 HG005975/HG/NHGRI NIH HHS/United States ; R37 DE016937/DE/NIDCR NIH HHS/United States ; UH3 DK083993/DK/NIDDK NIH HHS/United States ; R01DE021574/DE/NIDCR NIH HHS/United States ; R01 HG004885/HG/NHGRI NIH HHS/United States ; U54 HG004968/HG/NHGRI NIH HHS/United States ; U54HG004973/HG/NHGRI NIH HHS/United States ; UH2 AI083263/AI/NIAID NIH HHS/United States ; R01HG005171/HG/NHGRI NIH HHS/United States ; T32AI007528/AI/NIAID NIH HHS/United States ; R01HG004906/HG/NHGRI NIH HHS/United States ; U54HG003079/HG/NHGRI NIH HHS/United States ; RC1 DE020298/DE/NIDCR NIH HHS/United States ; DP2 OD001500/OD/NIH HHS/United States ; R01 DE021574/DE/NIDCR NIH HHS/United States ; T32 GM087237/GM/NIGMS NIH HHS/United States ; R01 HG004908/HG/NHGRI NIH HHS/United States ; R01 HG004872/HG/NHGRI NIH HHS/United States ; R21 CA139193/CA/NCI NIH HHS/United States ; R01HG005975/HG/NHGRI NIH HHS/United States ; U01 DE016937/DE/NIDCR NIH HHS/United States ; R21CA139193/CA/NCI NIH HHS/United States ; R21 HG005811/HG/NHGRI NIH HHS/United States ; U54 HG003079/HG/NHGRI NIH HHS/United States ; R01 HG004853/HG/NHGRI NIH HHS/United States ; N01AI30071/AI/NIAID NIH HHS/United States ; U54 HG004969/HG/NHGRI NIH HHS/United States ; R01HG00485/HG/NHGRI NIH HHS/United States ; R01HG004853/HG/NHGRI NIH HHS/United States ; UH3 AI083263/AI/NIAID NIH HHS/United States ; UH2DK083990/DK/NIDDK NIH HHS/United States ; U54HG004968/HG/NHGRI NIH HHS/United States ; R01 HG004906/HG/NHGRI NIH HHS/United States ; R01HG005969/HG/NHGRI NIH HHS/United States ; R01 HG004877/HG/NHGRI NIH HHS/United States ; P30 DE020751/DE/NIDCR NIH HHS/United States ; R01 HG005172/HG/NHGRI NIH HHS/United States ; UH2AR057506/AR/NIAMS NIH HHS/United States ; }, mesh = {Adolescent ; Adult ; Bacteria/*genetics ; Female ; Humans ; Male ; *Metagenome ; Metagenomics/*methods ; RNA, Ribosomal, 16S/genetics ; Reference Standards ; Statistics as Topic ; Young Adult ; }, abstract = {A variety of microbial communities and their genes (the microbiome) exist throughout the human body, with fundamental roles in human health and disease. The National Institutes of Health (NIH)-funded Human Microbiome Project Consortium has established a population-scale framework to develop metagenomic protocols, resulting in a broad range of quality-controlled resources and data including standardized methods for creating, processing and interpreting distinct types of high-throughput metagenomic data available to the scientific community. Here we present resources from a population of 242 healthy adults sampled at 15 or 18 body sites up to three times, which have generated 5,177 microbial taxonomic profiles from 16S ribosomal RNA genes and over 3.5 terabases of metagenomic sequence so far. In parallel, approximately 800 reference strains isolated from the human body have been sequenced. Collectively, these data represent the largest resource describing the abundance and variety of the human microbiome, while providing a framework for current and future studies.}, }
@article {pmid22699609, year = {2012}, author = {, }, title = {Structure, function and diversity of the healthy human microbiome.}, journal = {Nature}, volume = {486}, number = {7402}, pages = {207-214}, pmid = {22699609}, issn = {1476-4687}, support = {R01HG004856/HG/NHGRI NIH HHS/United States ; R01HG004908/HG/NHGRI NIH HHS/United States ; P30DE020751/DE/NIDCR NIH HHS/United States ; R21HG005811/HG/NHGRI NIH HHS/United States ; R01HG005172/HG/NHGRI NIH HHS/United States ; UH3DK083993/DK/NIDDK NIH HHS/United States ; R01 HG005969/HG/NHGRI NIH HHS/United States ; R01HG004900/HG/NHGRI NIH HHS/United States ; UH2 DK083990/DK/NIDDK NIH HHS/United States ; N01HG62088/HG/NHGRI NIH HHS/United States ; R01 HG004857/HG/NHGRI NIH HHS/United States ; U54 HG004973/HG/NHGRI NIH HHS/United States ; U01DE016937/DE/NIDCR NIH HHS/United States ; UH2 AR057504/AR/NIAMS NIH HHS/United States ; U54HG004969/HG/NHGRI NIH HHS/United States ; T32 AI007528/AI/NIAID NIH HHS/United States ; U54 HG003067/HG/NHGRI NIH HHS/United States ; U54HG003273/HG/NHGRI NIH HHS/United States ; R01HG004877/HG/NHGRI NIH HHS/United States ; R01 HG004900/HG/NHGRI NIH HHS/United States ; DP2OD001500/OD/NIH HHS/United States ; R01HG004885/HG/NHGRI NIH HHS/United States ; R01HG004872/HG/NHGRI NIH HHS/United States ; R01 HG004856/HG/NHGRI NIH HHS/United States ; R01 HG005171/HG/NHGRI NIH HHS/United States ; UH3AI083263/AI/NIAID NIH HHS/United States ; UH2 AR057506/AR/NIAMS NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; UH2AR057504/AR/NIAMS NIH HHS/United States ; U01HG004866/HG/NHGRI NIH HHS/United States ; U54HG003067/HG/NHGRI NIH HHS/United States ; U54 AI084844/AI/NIAID NIH HHS/United States ; UH3AR057504/AR/NIAMS NIH HHS/United States ; U54 HG003273/HG/NHGRI NIH HHS/United States ; UH2AI083263/AI/NIAID NIH HHS/United States ; U01 HG004866/HG/NHGRI NIH HHS/United States ; U54AI084844/AI/NIAID NIH HHS/United States ; R01 HG005975/HG/NHGRI NIH HHS/United States ; R37 DE016937/DE/NIDCR NIH HHS/United States ; UH3 DK083993/DK/NIDDK NIH HHS/United States ; R01DE021574/DE/NIDCR NIH HHS/United States ; R01 HG004885/HG/NHGRI NIH HHS/United States ; U54 HG004968/HG/NHGRI NIH HHS/United States ; U54HG004973/HG/NHGRI NIH HHS/United States ; R01HG004857/HG/NHGRI NIH HHS/United States ; UH2 AI083263/AI/NIAID NIH HHS/United States ; R01HG005171/HG/NHGRI NIH HHS/United States ; T32AI007528/AI/NIAID NIH HHS/United States ; R01HG004906/HG/NHGRI NIH HHS/United States ; U54HG003079/HG/NHGRI NIH HHS/United States ; RC1 DE020298/DE/NIDCR NIH HHS/United States ; DP2 OD001500/OD/NIH HHS/United States ; R01 DE021574/DE/NIDCR NIH HHS/United States ; T32 GM087237/GM/NIGMS NIH HHS/United States ; R01 HG004908/HG/NHGRI NIH HHS/United States ; R01 HG004872/HG/NHGRI NIH HHS/United States ; R21 CA139193/CA/NCI NIH HHS/United States ; R01HG005975/HG/NHGRI NIH HHS/United States ; U01 DE016937/DE/NIDCR NIH HHS/United States ; R21CA139193/CA/NCI NIH HHS/United States ; R21 HG005811/HG/NHGRI NIH HHS/United States ; U54 HG003079/HG/NHGRI NIH HHS/United States ; R01 HG004853/HG/NHGRI NIH HHS/United States ; N01AI30071/AI/NIAID NIH HHS/United States ; U54 HG004969/HG/NHGRI NIH HHS/United States ; R01HG004853/HG/NHGRI NIH HHS/United States ; UH3 AI083263/AI/NIAID NIH HHS/United States ; UH2DK083990/DK/NIDDK NIH HHS/United States ; U54HG004968/HG/NHGRI NIH HHS/United States ; RC1DE0202098/DE/NIDCR NIH HHS/United States ; R01 HG004906/HG/NHGRI NIH HHS/United States ; R01HG005969/HG/NHGRI NIH HHS/United States ; R01 HG004877/HG/NHGRI NIH HHS/United States ; P30 DE020751/DE/NIDCR NIH HHS/United States ; R01 HG005172/HG/NHGRI NIH HHS/United States ; UH2AR057506/AR/NIAMS NIH HHS/United States ; }, mesh = {Adolescent ; Adult ; Bacteria/*classification/genetics ; *Biodiversity ; Ecosystem ; Female ; *Health ; Humans ; Male ; Metabolic Networks and Pathways/physiology ; *Metagenome ; Metagenomics ; Phenotype ; RNA, Ribosomal, 16S/genetics ; Young Adult ; }, abstract = {Studies of the human microbiome have revealed that even healthy individuals differ remarkably in the microbes that occupy habitats such as the gut, skin and vagina. Much of this diversity remains unexplained, although diet, environment, host genetics and early microbial exposure have all been implicated. Accordingly, to characterize the ecology of human-associated microbial communities, the Human Microbiome Project has analysed the largest cohort and set of distinct, clinically relevant body habitats so far. We found the diversity and abundance of each habitat's signature microbes to vary widely even among healthy subjects, with strong niche specialization both within and among individuals. The project encountered an estimated 81-99% of the genera, enzyme families and community configurations occupied by the healthy Western microbiome. Metagenomic carriage of metabolic pathways was stable among individuals despite variation in community structure, and ethnic/racial background proved to be one of the strongest associations of both pathways and microbes with clinical metadata. These results thus delineate the range of structural and functional configurations normal in the microbial communities of a healthy population, enabling future characterization of the epidemiology, ecology and translational applications of the human microbiome.}, }
@article {pmid22698087, year = {2012}, author = {Segata, N and Haake, SK and Mannon, P and Lemon, KP and Waldron, L and Gevers, D and Huttenhower, C and Izard, J}, title = {Composition of the adult digestive tract bacterial microbiome based on seven mouth surfaces, tonsils, throat and stool samples.}, journal = {Genome biology}, volume = {13}, number = {6}, pages = {R42}, pmid = {22698087}, issn = {1474-760X}, support = {HG004969/HG/NHGRI NIH HHS/United States ; DE020751/DE/NIDCR NIH HHS/United States ; HG005969/HG/NHGRI NIH HHS/United States ; CA139193/CA/NCI NIH HHS/United States ; DE020298/DE/NIDCR NIH HHS/United States ; DE021574/DE/NIDCR NIH HHS/United States ; }, mesh = {Actinobacteria/classification/genetics/isolation &amp; purification ; Adolescent ; Adult ; Bacterial Typing Techniques/methods ; Bacteroidetes/classification/genetics/isolation &amp; purification ; *Biota ; Feces/*microbiology ; Female ; Genes, rRNA ; Humans ; Male ; *Metagenome ; Mouth/*microbiology ; Palatine Tonsil/*microbiology ; Pharynx/*microbiology ; Phylogeny ; RNA, Ribosomal, 16S/analysis/genetics ; Saliva/microbiology ; Veillonellaceae/classification/genetics/isolation &amp; purification ; Young Adult ; }, abstract = {BACKGROUND: To understand the relationship between our bacterial microbiome and health, it is essential to define the microbiome in the absence of disease. The digestive tract includes diverse habitats and hosts the human body's greatest bacterial density. We describe the bacterial community composition of ten digestive tract sites from more than 200 normal adults enrolled in the Human Microbiome Project, and metagenomically determined metabolic potentials of four representative sites.<br><br>RESULTS: The microbiota of these diverse habitats formed four groups based on similar community compositions: buccal mucosa, keratinized gingiva, hard palate; saliva, tongue, tonsils, throat; sub- and supra-gingival plaques; and stool. Phyla initially identified from environmental samples were detected throughout this population, primarily TM7, SR1, and Synergistetes. Genera with pathogenic members were well-represented among this disease-free cohort. Tooth-associated communities were distinct, but not entirely dissimilar, from other oral surfaces. The Porphyromonadaceae, Veillonellaceae and Lachnospiraceae families were common to all sites, but the distributions of their genera varied significantly. Most metabolic processes were distributed widely throughout the digestive tract microbiota, with variations in metagenomic abundance between body habitats. These included shifts in sugar transporter types between the supragingival plaque, other oral surfaces, and stool; hydrogen and hydrogen sulfide production were also differentially distributed.<br><br>CONCLUSIONS: The microbiomes of ten digestive tract sites separated into four types based on composition. A core set of metabolic pathways was present across these diverse digestive tract habitats. These data provide a critical baseline for future studies investigating local and systemic diseases affecting human health.}, }
@article {pmid22688726, year = {2012}, author = {Culligan, EP and Marchesi, JR and Hill, C and Sleator, RD}, title = {Mining the human gut microbiome for novel stress resistance genes.}, journal = {Gut microbes}, volume = {3}, number = {4}, pages = {394-397}, pmid = {22688726}, issn = {1949-0984}, mesh = {Bacteria/*drug effects/*genetics ; Computational Biology ; Gastrointestinal Tract/*microbiology ; Genes, Bacterial ; Genomics ; Humans ; *Metagenome ; *Osmotic Pressure ; Stress, Physiological ; }, abstract = {With the rapid advances in sequencing technologies in recent years, the human genome is now considered incomplete without the complementing microbiome, which outnumbers human genes by a factor of one hundred. The human microbiome, and more specifically the gut microbiome, has received considerable attention and research efforts over the past decade. Many studies have identified and quantified "who is there?," while others have determined some of their functional capacity, or "what are they doing?" In a recent study, we identified novel salt-tolerance loci from the human gut microbiome using combined functional metagenomic and bioinformatics based approaches. Herein, we discuss the identified loci, their role in salt-tolerance and their importance in the context of the gut environment. We also consider the utility and power of functional metagenomics for mining such environments for novel genes and proteins, as well as the implications and possible applications for future research.}, }
@article {pmid22683415, year = {2012}, author = {Hickey, RJ and Zhou, X and Pierson, JD and Ravel, J and Forney, LJ}, title = {Understanding vaginal microbiome complexity from an ecological perspective.}, journal = {Translational research : the journal of laboratory and clinical medicine}, volume = {160}, number = {4}, pages = {267-282}, pmid = {22683415}, issn = {1878-1810}, support = {U01 AI070921/AI/NIAID NIH HHS/United States ; UH2 AI083264/AI/NIAID NIH HHS/United States ; UO1 AI070921/AI/NIAID NIH HHS/United States ; }, mesh = {Aging ; Bacteria/*classification ; Ethnicity ; Female ; Humans ; Vagina/*microbiology ; Vaginosis, Bacterial/microbiology ; }, abstract = {The various microbiota normally associated with the human body have an important influence on human development, physiology, immunity, and nutrition. This is certainly true for the vagina wherein communities of mutualistic bacteria constitute the first line of defense for the host by excluding invasive, nonindigenous organisms that may cause disease. In recent years much has been learned about the bacterial species composition of these communities and how they differ between individuals of different ages and ethnicities. A deeper understanding of their origins and the interrelationships of constituent species is needed to understand how and why they change over time or in response to changes in the host environment. Moreover, there are few unifying theories to explain the ecological dynamics of vaginal ecosystems as they respond to disturbances caused by menses and human activities such as intercourse, douching, and other habits and practices. This fundamental knowledge is needed to diagnose and assess risk to disease. Here we summarize what is known about the species composition, structure, and function of bacterial communities in the human vagina and the applicability of ecological models of community structure and function to understanding the dynamics of this and other ecosystems that comprise the human microbiome.}, }
@article {pmid22683238, year = {2012}, author = {Dave, M and Higgins, PD and Middha, S and Rioux, KP}, title = {The human gut microbiome: current knowledge, challenges, and future directions.}, journal = {Translational research : the journal of laboratory and clinical medicine}, volume = {160}, number = {4}, pages = {246-257}, doi = {10.1016/j.trsl.2012.05.003}, pmid = {22683238}, issn = {1878-1810}, mesh = {Adaptive Immunity/physiology ; Bacteria/*classification ; Computational Biology ; Gastrointestinal Tract/*microbiology ; Humans ; Immunity, Innate/physiology ; }, abstract = {The Human Genome Project was completed a decade ago, leaving a legacy of process, tools, and infrastructure now being turned to the study of the microbes that reside in and on the human body as determinants of health and disease, and has been branded "The Human Microbiome Project." Of the various niches under investigation, the human gut houses the most complex and abundant microbial community and is an arena for important host-microbial interactions that have both local and systemic impact. Initial studies of the human microbiome have been largely descriptive, a testing ground for innovative molecular techniques and new hypotheses. Methods for studying the microbiome have quickly evolved from low-resolution surveys of microbial community structure to high-definition description of composition, function, and ecology. Next-generation sequencing technologies combined with advanced bioinformatics place us at the doorstep of revolutionary insight into the composition, capability, and activity of the human intestinal microbiome. Renewed efforts to cultivate previously "uncultivable" microbes will be important to the overall understanding of gut ecology. There remain numerous methodological challenges to the effective study and understanding of the gut microbiome, largely relating to study design, sample collection, and the number of predictor variables. Strategic collaboration of clinicians, microbiologists, molecular biologists, computational scientists, and bioinformaticians is the ideal paradigm for success in this field. Meaningful interpretation of the gut microbiome requires that host genetic and environmental influences be controlled or accounted for. Understanding the gut microbiome in healthy humans is a foundation for discovering its influence in various important gastrointestinal and nutritional diseases (eg, inflammatory bowel disease, diabetes, and obesity), and for rational translation to human health gains.}, }
@article {pmid22675588, year = {2011}, author = {Earl, AM and Desjardins, CA and Fitzgerald, MG and Arachchi, HM and Zeng, Q and Mehta, T and Griggs, A and Birren, BW and Toney, NC and Carr, J and Posey, J and Butler, WR}, title = {High quality draft genome sequence of Segniliparus rugosus CDC 945(T)= (ATCC BAA-974(T)).}, journal = {Standards in genomic sciences}, volume = {5}, number = {3}, pages = {389-397}, pmid = {22675588}, issn = {1944-3277}, support = {HHSN272200900017C/AI/NIAID NIH HHS/United States ; U54 HG004969/HG/NHGRI NIH HHS/United States ; }, abstract = {Segniliparus rugosus represents one of two species in the genus Segniliparus, the sole genus in the family Segniliparaceae. A unique and interesting feature of this family is the presence of extremely long carbon-chain length mycolic acids bound in the cell wall. S. rugosus is also a medically important species because it is an opportunistic pathogen associated with mammalian lung disease. This report represents the second species in the genus to have its genome sequenced. The 3,567,567 bp long genome with 3,516 protein-coding and 49 RNA genes is part of the NIH Roadmap for Medical Research, Human Microbiome Project.}, }
@article {pmid22674335, year = {2012}, author = {Costello, EK and Stagaman, K and Dethlefsen, L and Bohannan, BJ and Relman, DA}, title = {The application of ecological theory toward an understanding of the human microbiome.}, journal = {Science (New York, N.Y.)}, volume = {336}, number = {6086}, pages = {1255-1262}, pmid = {22674335}, issn = {1095-9203}, support = {DP1 OD000964/OD/NIH HHS/United States ; R01 OD011116/OD/NIH HHS/United States ; R01 GM095385/GM/NIGMS NIH HHS/United States ; R01GM095385/GM/NIGMS NIH HHS/United States ; DP1OD000964/OD/NIH HHS/United States ; T32 GM007413/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Anti-Bacterial Agents/pharmacology/*therapeutic use ; Bacterial Infections/*microbiology ; Biodiversity ; Ecology ; *Ecosystem ; Gastrointestinal Tract/*microbiology ; *Host-Pathogen Interactions ; Humans ; Infant, Newborn ; *Metagenome ; Selection, Genetic ; Symbiosis ; }, abstract = {The human-microbial ecosystem plays a variety of important roles in human health and disease. Each person can be viewed as an island-like "patch" of habitat occupied by microbial assemblages formed by the fundamental processes of community ecology: dispersal, local diversification, environmental selection, and ecological drift. Community assembly theory, and metacommunity theory in particular, provides a framework for understanding the ecological dynamics of the human microbiome, such as compositional variability within and between hosts. We explore three core scenarios of human microbiome assembly: development in infants, representing assembly in previously unoccupied habitats; recovery from antibiotics, representing assembly after disturbance; and invasion by pathogens, representing assembly in the context of invasive species. Judicious application of ecological theory may lead to improved strategies for restoring and maintaining the microbiota and the crucial health-associated ecosystem services that it provides.}, }
@article {pmid22674333, year = {2012}, author = {Balter, M}, title = {Taking stock of the human microbiome and disease.}, journal = {Science (New York, N.Y.)}, volume = {336}, number = {6086}, pages = {1246-1247}, doi = {10.1126/science.336.6086.1246}, pmid = {22674333}, issn = {1095-9203}, mesh = {Biomedical Research ; *Disease ; Genomics ; *Health ; Humans ; *Metagenome ; Probiotics ; Research Support as Topic ; Sequence Analysis, DNA ; }, }
@article {pmid22647049, year = {2012}, author = {Gosalbes, MJ and Abellan, JJ and Durbán, A and Pérez-Cobas, AE and Latorre, A and Moya, A}, title = {Metagenomics of human microbiome: beyond 16s rDNA.}, journal = {Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases}, volume = {18 Suppl 4}, number = {}, pages = {47-49}, doi = {10.1111/j.1469-0691.2012.03865.x}, pmid = {22647049}, issn = {1469-0691}, mesh = {DNA, Ribosomal/chemistry/genetics ; Humans ; *Metagenome ; Metagenomics/*methods ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA/methods ; Transcriptome ; }, abstract = {The gut microbiota presents a symbiotic relationship with the human host playing a beneficial role in human health. Since its establishment, the bacterial community is subjected to the influence of many different factors that shape its composition within each individual. However, an important convergence is observed at functional level in the gut microbiota. A metatranscriptomic study of healthy individuals showed homogeneity in the composition of the active microbiota that increased further at functional level.}, }
@article {pmid22635997, year = {2012}, author = {Wu, YW and Rho, M and Doak, TG and Ye, Y}, title = {Oral spirochetes implicated in dental diseases are widespread in normal human subjects and carry extremely diverse integron gene cassettes.}, journal = {Applied and environmental microbiology}, volume = {78}, number = {15}, pages = {5288-5296}, pmid = {22635997}, issn = {1098-5336}, mesh = {Base Pairing ; Base Sequence ; Cluster Analysis ; Computational Biology/*methods ; Computer Simulation ; DNA Primers/genetics ; Humans ; Integrons/*genetics ; Metagenome/*genetics ; Molecular Sequence Data ; Phylogeny ; Polymerase Chain Reaction ; Stomatognathic Diseases/*microbiology ; Treponema/*genetics ; }, abstract = {The NIH Human Microbiome Project (HMP) has produced several hundred metagenomic data sets, allowing studies of the many functional elements in human-associated microbial communities. Here, we survey the distribution of oral spirochetes implicated in dental diseases in normal human individuals, using recombination sites associated with the chromosomal integron in Treponema genomes, taking advantage of the multiple copies of the integron recombination sites (repeats) in the genomes, and using a targeted assembly approach that we have developed. We find that integron-containing Treponema species are present in ∼80% of the normal human subjects included in the HMP. Further, we are able to de novo assemble the integron gene cassettes using our constrained assembly approach, which employs a unique application of the de Bruijn graph assembly information; most of these cassette genes were not assembled in whole-metagenome assemblies and could not be identified by mapping sequencing reads onto the known reference Treponema genomes due to the dynamic nature of integron gene cassettes. Our study significantly enriches the gene pool known to be carried by Treponema chromosomal integrons, totaling 826 (598 97% nonredundant) genes. We characterize the functions of these gene cassettes: many of these genes have unknown functions. The integron gene cassette arrays found in the human microbiome are extraordinarily dynamic, with different microbial communities sharing only a small number of common genes.}, }
@article {pmid22607899, year = {2012}, author = {Maiden, MC and Frosch, M}, title = {Can we, should we, eradicate the meningococcus?.}, journal = {Vaccine}, volume = {30 Suppl 2}, number = {6}, pages = {B52-6}, pmid = {22607899}, issn = {1873-2518}, support = {087622/WT_/Wellcome Trust/United Kingdom ; }, mesh = {Animals ; *Disease Eradication ; *Genetic Variation ; Global Health ; Humans ; Meningococcal Infections/*epidemiology/*prevention &amp; control ; Neisseria meningitidis/*classification/*isolation &amp; purification ; }, abstract = {The eradication of infectious agents is an attractive means of disease control that, to date, has been achieved for only one human pathogen, the smallpox virus. The introduction of vaccines against Neisseria meningitidis into immunisation schedules, and particularly the conjugate polysaccharide vaccines which can interrupt transmission, raises the question of whether disease caused by this obligate human bacterium can be controlled, eliminated, or even eradicated. The limited number of meningococcal serogroups, lack of an animal reservoir, and importance of meningococcal disease are considerations in favour of eradication; however, the commensal nature of most infections, the high diversity of meningococcal populations, and the lack of comprehensive vaccines are all factors that suggest that this is not feasible. Indeed, any such attempt might be harmful by perturbing the human microbiome and its interaction with the immune system. On balance, the control and possible elimination of disease caused by particular disease-associated meningococcal genotypes is a more achievable and worthwhile goal.}, }
@article {pmid22589385, year = {2012}, author = {Borenstein, E}, title = {Computational systems biology and in silico modeling of the human microbiome.}, journal = {Briefings in bioinformatics}, volume = {13}, number = {6}, pages = {769-780}, doi = {10.1093/bib/bbs022}, pmid = {22589385}, issn = {1477-4054}, mesh = {*Computer Simulation ; Humans ; *Metagenome ; Metagenomics ; Systems Biology/*methods ; }, abstract = {The human microbiome is a complex biological system with numerous interacting components across multiple organizational levels. The assembly, ecology and dynamics of the microbiome and its contribution to the development, physiology and nutrition of the host are clearly affected not only by the set of genes or species in the microbiome but also by the way these genes are linked across numerous pathways and by the interactions between the various species. To date, however, most studies of the human microbiome have focused on characterizing the composition of the microbiome and on comparative analyses, whereas significantly less effort has been directed at elucidating, characterizing and modeling these interactions and on studying the microbiome as a complex, interconnected and cohesive system. Here, specifically, I highlight the pressing need for the development of predictive system-level models and for a system-level understanding of the microbiome, and discuss potential computational frameworks for metagenomic-based modeling of the microbiome at the cellular, ecological and supra-organismal level. I review some preliminary attempts at constructing such models and examine the challenges and hurdles that such modeling efforts face. I also discuss possible future applications and research avenues that such metagenomic systems biology and predictive system-level models may facilitate.}, }
@article {pmid22583485, year = {2012}, author = {Pride, DT and Salzman, J and Relman, DA}, title = {Comparisons of clustered regularly interspaced short palindromic repeats and viromes in human saliva reveal bacterial adaptations to salivary viruses.}, journal = {Environmental microbiology}, volume = {14}, number = {9}, pages = {2564-2576}, pmid = {22583485}, issn = {1462-2920}, support = {DP1 OD000964/OD/NIH HHS/United States ; K08 AI085028/AI/NIAID NIH HHS/United States ; }, mesh = {Ecosystem ; Humans ; Inverted Repeat Sequences/*genetics ; Metagenome/genetics ; Saliva/*microbiology/*virology ; Streptococcus/*genetics/*virology ; Viruses/*genetics ; }, abstract = {Explorations of human microbiota have provided substantial insight into microbial community composition; however, little is known about interactions between various microbial components in human ecosystems. In response to the powerful impact of viral predation, bacteria have acquired potent defences, including an adaptive immune response based on the clustered regularly interspaced short palindromic repeats (CRISPRs)/Cas system. To improve our understanding of the interactions between bacteria and their viruses in humans, we analysed 13 977 streptococcal CRISPR sequences and compared them with 2 588 172 virome reads in the saliva of four human subjects over 17 months. We found a diverse array of viruses and CRISPR spacers, many of which were specific to each subject and time point. There were numerous viral sequences matching CRISPR spacers; these matches were highly specific for salivary viruses. We determined that spacers and viruses coexist at the same time, which suggests that streptococcal CRISPR/Cas systems are under constant pressure from salivary viruses. CRISPRs in some subjects were just as likely to match viral sequences from other subjects as they were to match viruses from the same subject. Because interactions between bacteria and viruses help to determine the structure of bacterial communities, CRISPR-virus analyses are likely to provide insight into the forces shaping the human microbiome.}, }
@article {pmid22577297, year = {2012}, author = {Liu, Z and Bensmail, H and Tan, M}, title = {Efficient feature selection and multiclass classification with integrated instance and model based learning.}, journal = {Evolutionary bioinformatics online}, volume = {8}, number = {}, pages = {197-205}, pmid = {22577297}, issn = {1176-9343}, support = {R03 CA133899/CA/NCI NIH HHS/United States ; }, abstract = {Multiclass classification and feature (variable) selections are commonly encountered in many biological and medical applications. However, extending binary classification approaches to multiclass problems is not trivial. Instance-based methods such as the K nearest neighbor (KNN) can naturally extend to multiclass problems and usually perform well with unbalanced data, but suffer from the curse of dimensionality. Their performance is degraded when applied to high dimensional data. On the other hand, model-based methods such as logistic regression require the decomposition of the multiclass problem into several binary problems with one-vs.-one or one-vs.-rest schemes. Even though they can be applied to high dimensional data with L(1) or L(p) penalized methods, such approaches can only select independent features and the features selected with different binary problems are usually different. They also produce unbalanced classification problems with one vs. the rest scheme even if the original multiclass problem is balanced.By combining instance-based and model-based learning, we propose an efficient learning method with integrated KNN and constrained logistic regression (KNNLog) for simultaneous multiclass classification and feature selection. Our proposed method simultaneously minimizes the intra-class distance and maximizes the interclass distance with fewer estimated parameters. It is very efficient for problems with small sample size and unbalanced classes, a case common in many real applications. In addition, our model-based feature selection methods can identify highly correlated features simultaneously avoiding the multiplicity problem due to multiple tests. The proposed method is evaluated with simulation and real data including one unbalanced microRNA dataset for leukemia and one multiclass metagenomic dataset from the Human Microbiome Project (HMP). It performs well with limited computational experiments.}, }
@article {pmid22574119, year = {2012}, author = {Sanchez, LM and Wong, WR and Riener, RM and Schulze, CJ and Linington, RG}, title = {Examining the fish microbiome: vertebrate-derived bacteria as an environmental niche for the discovery of unique marine natural products.}, journal = {PloS one}, volume = {7}, number = {5}, pages = {e35398}, pmid = {22574119}, issn = {1932-6203}, support = {U01 TW006634/TW/FIC NIH HHS/United States ; 2R25GM05803-12/GM/NIGMS NIH HHS/United States ; TW006634/TW/FIC NIH HHS/United States ; }, mesh = {Animals ; Bacteria/classification/growth &amp; development/*isolation &amp; purification/*metabolism ; Biodiversity ; Biological Products/*metabolism ; Culture Techniques ; *Drug Discovery ; Fishes/*microbiology ; Intestines/microbiology ; *Metagenome ; Oceans and Seas ; Phylogeny ; }, abstract = {Historically, marine invertebrates have been a prolific source of unique natural products, with a diverse array of biological activities. Recent studies of invertebrate-associated microbial communities are revealing microorganisms as the true producers of many of these compounds. Inspired by the human microbiome project, which has highlighted the human intestine as a unique microenvironment in terms of microbial diversity, we elected to examine the bacterial communities of fish intestines (which we have termed the fish microbiome) as a new source of microbial and biosynthetic diversity for natural products discovery. To test the hypothesis that the fish microbiome contains microorganisms with unique capacity for biosynthesizing natural products, we examined six species of fish through a combination of dissection and culture-dependent evaluation of intestinal microbial communities. Using isolation media designed to enrich for marine Actinobacteria, we have found three main clades that show taxonomic divergence from known strains, several of which are previously uncultured. Extracts from these strains exhibit a wide range of activities against both gram-positive and gram-negative human pathogens, as well as several fish pathogens. Exploration of one of these extracts has identified the novel bioactive lipid sebastenoic acid as an anti-microbial agent, with activity against Staphylococcus aureus, Bacillus subtilis, Enterococcus faecium, and Vibrio mimicus.}, }
@article {pmid22573192, year = {2012}, author = {Albenberg, LG and Lewis, JD and Wu, GD}, title = {Food and the gut microbiota in inflammatory bowel diseases: a critical connection.}, journal = {Current opinion in gastroenterology}, volume = {28}, number = {4}, pages = {314-320}, pmid = {22573192}, issn = {1531-7056}, support = {R01 DK089472/DK/NIDDK NIH HHS/United States ; UH2 DK083981/DK/NIDDK NIH HHS/United States ; UH3 DK083981/DK/NIDDK NIH HHS/United States ; UH2/3 DK083981/DK/NIDDK NIH HHS/United States ; K24 DK078228/DK/NIDDK NIH HHS/United States ; R01 AI39368/AI/NIAID NIH HHS/United States ; R01 GM103591/GM/NIGMS NIH HHS/United States ; R01 AI039368/AI/NIAID NIH HHS/United States ; }, mesh = {DNA, Bacterial/genetics ; *Diet ; Genetic Predisposition to Disease ; Humans ; Inflammatory Bowel Diseases/genetics/*microbiology ; Intestines/*microbiology ; Metagenome/genetics/*physiology ; Sequence Analysis, DNA/methods ; }, abstract = {PURPOSE OF REVIEW: The inflammatory bowel diseases (IBD) are chronic inflammatory diseases of the gastrointestinal tract apparently due to an abnormal immune response to environmental factors in genetically susceptible hosts. The composition of the gut microbiota is thought to be a critical environmental factor in IBD, and recent evidence suggests a connection between diet and the intestinal bacteria. In this review, we describe the current evidence regarding the impact of diet on the gut microbiome and how this may be relevant to the pathogenesis of IBD.<br><br>RECENT FINDINGS: Novel culture-independent DNA sequencing technology has revolutionized the approach to the characterization of intestinal bacterial communities. Recent studies have demonstrated an association between the diet and the human microbiome. Because the development of a 'dysbiotic' microbiota is thought to be involved in the pathogenesis of IBD, diet is being investigated as an important etiologic factor.<br><br>SUMMARY: The recent studies highlighting the impact of diet on the gut microbiome provide a strong rationale for further investigation of the link between diet, the gut microbiome, and the development of IBD. Such studies may provide novel information about disease pathogenesis as well as identify new therapeutic alternatives for patients suffering from IBD.}, }
@article {pmid22550247, year = {2012}, author = {Blaser, MJ}, title = {Equilibria of humans and our indigenous microbiota affecting asthma.}, journal = {Proceedings of the American Thoracic Society}, volume = {9}, number = {2}, pages = {69-71}, pmid = {22550247}, issn = {1943-5665}, support = {R01 GM063270/GM/NIGMS NIH HHS/United States ; R01GM63270/GM/NIGMS NIH HHS/United States ; }, mesh = {Asthma/*immunology/*microbiology/prevention &amp; control ; Helicobacter Infections/*immunology ; Helicobacter pylori/*immunology ; Humans ; *Metagenome ; Stomach/microbiology ; T-Lymphocytes, Regulatory/immunology/*microbiology ; }, abstract = {It is becoming increasingly clear that our residential microbes, the key constituents in the human microbiome, are centrally involved in many aspects of our physiology. In particular, the ancient and dominant gastric bacteria Helicobacter pylori are highly interactive with human physiology. In modern times, H. pylori has been disappearing, which consequently affects the interactions between luminal bacteria and epithelial, lymphoid, and neuroendocrine cells. A growing body of evidence indicates that H. pylori protects against childhood-onset asthma, probably through the gastric recruitment of regulatory T cells. The phenomenon of disappearing ancient microbiota may be a general paradigm driving the diseases of modernity.}, }
@article {pmid22541361, year = {2012}, author = {Ursell, LK and Clemente, JC and Rideout, JR and Gevers, D and Caporaso, JG and Knight, R}, title = {The interpersonal and intrapersonal diversity of human-associated microbiota in key body sites.}, journal = {The Journal of allergy and clinical immunology}, volume = {129}, number = {5}, pages = {1204-1208}, pmid = {22541361}, issn = {1097-6825}, support = {R01 HG004872-01/HG/NHGRI NIH HHS/United States ; T32 GM008759/GM/NIGMS NIH HHS/United States ; U01 HG004866-01/HG/NHGRI NIH HHS/United States ; U01 HG004866/HG/NHGRI NIH HHS/United States ; R01 HG004872/HG/NHGRI NIH HHS/United States ; T32 GM008759-01/GM/NIGMS NIH HHS/United States ; T32 GM142607/GM/NIGMS NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Female ; Homeostasis ; Host-Pathogen Interactions ; Humans ; Hypersensitivity/immunology/microbiology ; Immunity, Mucosal ; Inflammatory Bowel Diseases/immunology/microbiology ; Intestines/*microbiology ; *Metagenome ; Microbial Interactions ; Organ Specificity ; Respiratory System/*microbiology ; Skin/*microbiology ; Vagina/*microbiology ; }, abstract = {The human body harbors 10 to 100 trillion microbes, mainly bacteria in our gut, which greatly outnumber our own human cells. This bacterial assemblage, referred to as the human microbiota, plays a fundamental role in our well-being. Deviations from healthy microbial compositions (dysbiosis) have been linked with important human diseases, including inflammation-linked disorders, such as allergies, obesity, and inflammatory bowel disease. Characterizing the temporal variations and community membership of the healthy human microbiome is critical to accurately identify the significant deviations from normality that could be associated with disease states. However, the diversity of the human microbiome varies between body sites, between patients, and over time. Environmental differences have also been shown to play a role in shaping the human microbiome in different cultures, requiring that the healthy human microbiome be characterized across life spans, ethnicities, nationalities, cultures, and geographic locales. In this article we summarize our knowledge on the microbial composition of the 5 best-characterized body sites (gut, skin, oral, airways, and vagina), focusing on interpersonal and intrapersonal variations and our current understanding of the sources of this variation.}, }
@article {pmid22514642, year = {2012}, author = {Willner, D and Daly, J and Whiley, D and Grimwood, K and Wainwright, CE and Hugenholtz, P}, title = {Comparison of DNA extraction methods for microbial community profiling with an application to pediatric bronchoalveolar lavage samples.}, journal = {PloS one}, volume = {7}, number = {4}, pages = {e34605}, pmid = {22514642}, issn = {1932-6203}, mesh = {Bronchoalveolar Lavage Fluid/*chemistry ; DNA, Bacterial/*isolation &amp; purification ; Humans ; Principal Component Analysis ; Real-Time Polymerase Chain Reaction ; Staphylococcus/genetics ; }, abstract = {Barcoded amplicon sequencing is rapidly becoming a standard method for profiling microbial communities, including the human respiratory microbiome. While this approach has less bias than standard cultivation, several steps can introduce variation including the type of DNA extraction method used. Here we assessed five different extraction methods on pediatric bronchoalveolar lavage (BAL) samples and a mock community comprised of nine bacterial genera to determine method reproducibility and detection limits for these typically low complexity communities. Additionally, using the mock community, we were able to evaluate contamination and select a relative abundance cut-off threshold based on the geometric distribution that optimizes the trade off between detecting bona fide operational taxonomic units and filtering out spurious ones. Using this threshold, the majority of genera in the mock community were predictably detected by all extraction methods including the hard-to-lyse Gram-positive genus Staphylococcus. Differences between extraction methods were significantly greater than between technical replicates for both the mock community and BAL samples emphasizing the importance of using a standardized methodology for microbiome studies. However, regardless of method used, individual patients retained unique diagnostic profiles. Furthermore, despite being stored as raw frozen samples for over five years, community profiles from BAL samples were consistent with historical culturing results. The culture-independent profiling of these samples also identified a number of anaerobic genera that are gaining acceptance as being part of the respiratory microbiome. This study should help guide researchers to formulate sampling, extraction and analysis strategies for respiratory and other human microbiome samples.}, }
@article {pmid22486161, year = {2012}, author = {Koeppel, AF and Wu, M}, title = {Lineage-dependent ecological coherence in bacteria.}, journal = {FEMS microbiology ecology}, volume = {81}, number = {3}, pages = {574-582}, doi = {10.1111/j.1574-6941.2012.01387.x}, pmid = {22486161}, issn = {1574-6941}, mesh = {Actinobacteria/isolation &amp; purification ; Bacteria/*classification/genetics/*isolation &amp; purification ; Ecosystem ; Gastrointestinal Tract/microbiology ; Humans ; *Metagenome ; Obesity/microbiology ; Phylogeny ; Proteobacteria/isolation &amp; purification ; RNA, Ribosomal, 16S/genetics ; Skin/microbiology ; }, abstract = {Bacteria comprise an essential element of all ecosystems, including those present on and within the human body. Understanding bacterial diversity therefore offers enormous scientific and medical benefit, but significant questions remain regarding how best to characterize that diversity and organize it into biologically meaningful units. Bacterial communities are routinely characterized based on the relative abundances of taxa at the genus or even the phylum level, but the ecological coherence of these high-level taxonomic units is uncertain. Using human microbiota from the skin and gut as our model systems, we tested the ecological coherence of bacteria by investigating the habitat associations of bacteria at all levels of the taxonomic hierarchy. We observed four distinct taxonomic patterns of habitat association, reflecting different levels of ecological coherence among taxa. Our results support the hypothesis that deep-branch bacterial clades could be ecologically coherent and suggest that the phylogenetic depth of ecological coherence varies among the bacterial lineages and is an important factor to consider in studies of human microbiome associations.}, }
@article {pmid22473366, year = {2012}, author = {Johnson, CL and Versalovic, J}, title = {The human microbiome and its potential importance to pediatrics.}, journal = {Pediatrics}, volume = {129}, number = {5}, pages = {950-960}, pmid = {22473366}, issn = {1098-4275}, mesh = {Adolescent ; Adult ; Anti-Bacterial Agents/pharmacology ; Child ; Child, Preschool ; Enterocolitis, Necrotizing/microbiology ; Feeding Behavior ; Gastrointestinal Tract/microbiology ; Humans ; Infant ; Infant Formula ; Infant, Newborn ; Inflammatory Bowel Diseases/microbiology ; Irritable Bowel Syndrome/microbiology ; Metagenome/drug effects ; Milk, Human/microbiology ; *Pediatrics ; Probiotics ; Respiratory System/microbiology ; }, abstract = {The human body is home to more than 1 trillion microbes, with the gastrointestinal tract alone harboring a diverse array of commensal microbes that are believed to contribute to host nutrition, developmental regulation of intestinal angiogenesis, protection from pathogens, and development of the immune response. Recent advances in genome sequencing technologies and metagenomic analysis are providing a broader understanding of these resident microbes and highlighting differences between healthy and disease states. The aim of this review is to provide a detailed summary of current pediatric microbiome studies in the literature, in addition to highlighting recent findings and advancements in studies of the adult microbiome. This review also seeks to elucidate the development of, and factors that could lead to changes in, the composition and function of the human microbiome.}, }
@article {pmid23908833, year = {2012}, author = {Solt, I and Cohavy, O}, title = {The great obstetrical syndromes and the human microbiome-a new frontier.}, journal = {Rambam Maimonides medical journal}, volume = {3}, number = {2}, pages = {e0009}, pmid = {23908833}, issn = {2076-9172}, abstract = {Over the last two decades, advanced molecular genetics technology has enabled analysis of complex microbial communities and the study of microbial genomics. Interest has grown in characterizing the microbiome, defined as a collective microbial community and its extensive genome, as a clue to disease mechanisms. "The Human Microbiome Project," sponsored by the NIH Common Fund, was established to characterize the pathology-associated human microbiome in nasal passages, oral cavities, skin, the gastrointestinal tract, and the urogenital compartment. In particular, characterization of urogenital microbiota may elucidate etiologies of complex obstetrical syndromes and factors in fetal development that define risk for pathology in adulthood. This article summarizes recent findings defining the microbiome associated with the female urogenital compartment in child-bearing age women. We also describe our analysis of microbiome samples from the oral, vaginal, and rectal compartments in a cohort of pregnant women. Findings present technical considerations in the characterization of microbial diversity and composition associated with gestational diabetes as a model pregnancy-associated pathology.}, }
@article {pmid22457796, year = {2012}, author = {Yuan, S and Cohen, DB and Ravel, J and Abdo, Z and Forney, LJ}, title = {Evaluation of methods for the extraction and purification of DNA from the human microbiome.}, journal = {PloS one}, volume = {7}, number = {3}, pages = {e33865}, pmid = {22457796}, issn = {1932-6203}, support = {U01 AI070921/AI/NIAID NIH HHS/United States ; U01-AI070921/AI/NIAID NIH HHS/United States ; }, mesh = {Bacteria/*classification/genetics ; Biodiversity ; DNA, Bacterial/*isolation &amp; purification ; Humans ; }, abstract = {BACKGROUND: DNA extraction is an essential step in all cultivation-independent approaches to characterize microbial diversity, including that associated with the human body. A fundamental challenge in using these approaches has been to isolate DNA that is representative of the microbial community sampled.<br><br>In this study, we statistically evaluated six commonly used DNA extraction procedures using eleven human-associated bacterial species and a mock community that contained equal numbers of those eleven species. These methods were compared on the basis of DNA yield, DNA shearing, reproducibility, and most importantly representation of microbial diversity. The analysis of 16S rRNA gene sequences from a mock community showed that the observed species abundances were significantly different from the expected species abundances for all six DNA extraction methods used.<br><br>CONCLUSIONS/SIGNIFICANCE: Protocols that included bead beating and/or mutanolysin produced significantly better bacterial community structure representation than methods without both of them. The reproducibility of all six methods was similar, and results from different experimenters and different times were in good agreement. Based on the evaluations done it appears that DNA extraction procedures for bacterial community analysis of human associated samples should include bead beating and/or mutanolysin to effectively lyse cells.}, }
@article {pmid22411464, year = {2012}, author = {Cho, I and Blaser, MJ}, title = {The human microbiome: at the interface of health and disease.}, journal = {Nature reviews. Genetics}, volume = {13}, number = {4}, pages = {260-270}, pmid = {22411464}, issn = {1471-0064}, support = {5 P30 CA016087/CA/NCI NIH HHS/United States ; P30 CA016087/CA/NCI NIH HHS/United States ; 1UL1RR029893/RR/NCRR NIH HHS/United States ; R01 GM063270/GM/NIGMS NIH HHS/United States ; R01DK090989/DK/NIDDK NIH HHS/United States ; R01GM63270/GM/NIGMS NIH HHS/United States ; R01 DK090989/DK/NIDDK NIH HHS/United States ; UL1 RR029893/RR/NCRR NIH HHS/United States ; UH2 AR057506/AR/NIAMS NIH HHS/United States ; }, mesh = {Arthritis, Rheumatoid/etiology ; Bacteria/classification/genetics ; Colon/microbiology ; Gastrointestinal Tract/microbiology ; Genomics/methods ; Humans ; Inflammatory Bowel Diseases/microbiology ; Liver Diseases/etiology ; *Metagenome ; Obesity/etiology ; }, abstract = {Interest in the role of the microbiome in human health has burgeoned over the past decade with the advent of new technologies for interrogating complex microbial communities. The large-scale dynamics of the microbiome can be described by many of the tools and observations used in the study of population ecology. Deciphering the metagenome and its aggregate genetic information can also be used to understand the functional properties of the microbial community. Both the microbiome and metagenome probably have important functions in health and disease; their exploration is a frontier in human genetics.}, }
@article {pmid22410962, year = {2013}, author = {Fava, F and Gitau, R and Griffin, BA and Gibson, GR and Tuohy, KM and Lovegrove, JA}, title = {The type and quantity of dietary fat and carbohydrate alter faecal microbiome and short-chain fatty acid excretion in a metabolic syndrome 'at-risk' population.}, journal = {International journal of obesity (2005)}, volume = {37}, number = {2}, pages = {216-223}, doi = {10.1038/ijo.2012.33}, pmid = {22410962}, issn = {1476-5497}, mesh = {Adult ; Aged ; Bacteroides/isolation &amp; purification ; Bifidobacterium/isolation &amp; purification ; Blood Glucose/metabolism ; Cholesterol/blood ; Chromatography, Gas ; Colon/metabolism/*microbiology ; Diet ; *Dietary Carbohydrates ; *Dietary Fats ; Fatty Acids, Monounsaturated/metabolism ; Fatty Acids, Volatile/*metabolism ; Feces/*microbiology ; Female ; Fermentation ; Humans ; Male ; Metabolic Syndrome/epidemiology/etiology/metabolism/*microbiology ; Middle Aged ; Obesity/complications/epidemiology/metabolism/*microbiology ; Risk Assessment ; United Kingdom/epidemiology ; Vulnerable Populations ; }, abstract = {INTRODUCTION AND OBJECTIVES: An obese-type human microbiota with an increased Firmicutes:Bacteroidetes ratio has been described that may link the gut microbiome with obesity and metabolic syndrome (MetS) development. Dietary fat and carbohydrate are modifiable risk factors that may impact on MetS by altering the human microbiome composition. We determined the effect of the amount and type of dietary fat and carbohydrate on faecal bacteria and short chain fatty acid (SCFA) concentrations in people 'at risk' of MetS.<br><br>DESIGN: A total of 88 subjects at increased MetS risk were fed a high saturated fat diet (HS) for 4 weeks (baseline), then randomised onto one of the five experimental diets for 24 weeks: HS; high monounsaturated fat (MUFA)/high glycemic index (GI) (HM/HGI); high MUFA/low GI (HM/LGI); high carbohydrate (CHO)/high GI (HC/HGI); and high CHO/low GI (HC/LGI). Dietary intakes, MetS biomarkers, faecal bacteriology and SCFA concentrations were monitored.<br><br>RESULTS: High MUFA diets did not affect individual bacterial population numbers but reduced total bacteria and plasma total and LDL-cholesterol. The low fat, HC diets increased faecal Bifidobacterium (P=0.005, for HC/HGI; P=0.052, for HC/LGI) and reduced fasting glucose and cholesterol compared to baseline. HC/HGI also increased faecal Bacteroides (P=0.038), whereas HC/LGI and HS increased Faecalibacterium prausnitzii (P=0.022 for HC/HGI and P=0.018, for HS). Importantly, changes in faecal Bacteroides numbers correlated inversely with body weight (r=-0.64). A total bacteria reduction was observed for high fat diets HM/HGI and HM/LGI (P=0.023 and P=0.005, respectively) and HS increased faecal SCFA concentrations (P<0.01).<br><br>CONCLUSION: This study provides new evidence from a large-scale dietary intervention study that HC diets, irrespective of GI, can modulate human faecal saccharolytic bacteria, including bacteroides and bifidobacteria. Conversely, high fat diets reduced bacterial numbers, and in the HS diet, increased excretion of SCFA, which may suggest a compensatory mechanism to eliminate excess dietary energy.}, }
@article {pmid22404909, year = {2012}, author = {Hyman, RW and St Onge, RP and Kim, H and Tamaresis, JS and Miranda, M and Aparicio, AM and Fukushima, M and Pourmand, N and Giudice, LC and Davis, RW}, title = {Molecular probe technology detects bacteria without culture.}, journal = {BMC microbiology}, volume = {12}, number = {}, pages = {29}, pmid = {22404909}, issn = {1471-2180}, support = {HG000205/HG/NHGRI NIH HHS/United States ; }, mesh = {*Bacteria/genetics/isolation &amp; purification ; Computer Simulation ; Female ; Humans ; Microbiological Techniques/*methods ; *Molecular Probe Techniques ; Molecular Sequence Data ; Oligonucleotide Array Sequence Analysis ; Reproducibility of Results ; Vagina/microbiology ; }, abstract = {BACKGROUND: Our ultimate goal is to detect the entire human microbiome, in health and in disease, in a single reaction tube, and employing only commercially available reagents. To that end, we adapted molecular inversion probes to detect bacteria using solely a massively multiplex molecular technology. This molecular probe technology does not require growth of the bacteria in culture. Rather, the molecular probe technology requires only a sequence of forty sequential bases unique to the genome of the bacterium of interest. In this communication, we report the first results of employing our molecular probes to detect bacteria in clinical samples.<br><br>RESULTS: While the assay on Affymetrix GenFlex Tag16K arrays allows the multiplexing of the detection of the bacteria in each clinical sample, one Affymetrix GenFlex Tag16K array must be used for each clinical sample. To multiplex the clinical samples, we introduce a second, independent assay for the molecular probes employing Sequencing by Oligonucleotide Ligation and Detection. By adding one unique oligonucleotide barcode for each clinical sample, we combine the samples after processing, but before sequencing, and sequence them together.<br><br>CONCLUSIONS: Overall, we have employed 192 molecular probes representing 40 bacteria to detect the bacteria in twenty-one vaginal swabs as assessed by the Affymetrix GenFlex Tag16K assay and fourteen of those by the Sequencing by Oligonucleotide Ligation and Detection assay. The correlations among the assays were excellent.}, }
@article {pmid22367084, year = {2012}, author = {Buerger, S and Spoering, A and Gavrish, E and Leslin, C and Ling, L and Epstein, SS}, title = {Microbial scout hypothesis and microbial discovery.}, journal = {Applied and environmental microbiology}, volume = {78}, number = {9}, pages = {3229-3233}, pmid = {22367084}, issn = {1098-5336}, mesh = {Bacteria/classification/*growth &amp; development/*isolation &amp; purification ; Bacteriological Techniques/*methods ; *Biodiversity ; Humans ; Metagenome ; Molecular Sequence Data ; Sequence Analysis, DNA ; Soil Microbiology ; Time Factors ; Water Microbiology ; }, abstract = {In this study, we examine the temporal pattern of colony appearance during cultivation experiments, and whether this pattern could inform on optimizing the process of microbial discovery. In a series of long-term cultivation experiments, we observed an expected gradual increase over time of the total number of microbial isolates, culminating in a 700-fold colony count increase at 18 months. Conventional thought suggests that long-term incubations result in a culture collection enriched with species that are slow growing or rare, may be unavailable from short-term experiments, and likely are novel. However, after we examined the phylogenetic novelty of the isolates as a function of the time of their isolation, we found no correlation between the two. The probability of discovering either a new or rare species late in the incubation matched that of species isolated earlier. These outcomes are especially notable because of their generality: observations were essentially identical for marine and soil bacteria as well as for spore formers and non-spore formers. These findings are consistent with the idea of the stochastic awakening of dormant cells, thus lending support to the scout model. The process of microbial discovery is central to the study of environmental microorganisms and the human microbiome. While long-term incubation does not appear to increase the probability of discovering novel species, the technology enabling such incubations, i.e., single-cell cultivation, may still be the method of choice. While it does not necessarily allow more species to grow from a given inoculum, it minimizes the overall isolation effort and supplies needed.}, }
@article {pmid22355685, year = {2011}, author = {Stearns, JC and Lynch, MD and Senadheera, DB and Tenenbaum, HC and Goldberg, MB and Cvitkovitch, DG and Croitoru, K and Moreno-Hagelsieb, G and Neufeld, JD}, title = {Bacterial biogeography of the human digestive tract.}, journal = {Scientific reports}, volume = {1}, number = {}, pages = {170}, pmid = {22355685}, issn = {2045-2322}, support = {//Canadian Institutes of Health Research/Canada ; }, mesh = {Adult ; Bacteria/classification/genetics/*isolation &amp; purification ; Biodiversity ; Female ; Gastrointestinal Tract/*microbiology ; Humans ; Male ; *Metagenome/genetics ; Organ Specificity ; Phylogeny ; RNA, Bacterial/genetics ; RNA, Ribosomal, 16S/genetics ; }, abstract = {We present bacterial biogeography as sampled from the human gastrointestinal tract of four healthy subjects. This study generated >32 million paired-end sequences of bacterial 16S rRNA genes (V3 region) representing >95,000 unique operational taxonomic units (OTUs; 97% similarity clusters), with >99% Good's coverage for all samples. The highest OTU richness and phylogenetic diversity was found in the mouth samples. The microbial communities of multiple biopsy sites within the colon were highly similar within individuals and largely distinct from those in stool. Within an individual, OTU overlap among broad site definitions (mouth, stomach/duodenum, colon and stool) ranged from 32-110 OTUs, 25 of which were common to all individuals and included OTUs affiliated with Faecalibacterium prasnitzii and the TM7 phylum. This first comprehensive characterization of the abundant and rare microflora found along the healthy human digestive tract represents essential groundwork to investigate further how the human microbiome relates to health and disease.}, }
@article {pmid22355105, year = {2012}, author = {Minot, S and Grunberg, S and Wu, GD and Lewis, JD and Bushman, FD}, title = {Hypervariable loci in the human gut virome.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {109}, number = {10}, pages = {3962-3966}, pmid = {22355105}, issn = {1091-6490}, support = {UH2 DK083981/DK/NIDDK NIH HHS/United States ; T32AI060516/AI/NIAID NIH HHS/United States ; UH2DK083981/DK/NIDDK NIH HHS/United States ; P30 DK050306/DK/NIDDK NIH HHS/United States ; S10 RR024525/RR/NCRR NIH HHS/United States ; T32 AI060516/AI/NIAID NIH HHS/United States ; R01 AI039368/AI/NIAID NIH HHS/United States ; UL1RR024134/RR/NCRR NIH HHS/United States ; AI39368/AI/NIAID NIH HHS/United States ; S10RR024525/RR/NCRR NIH HHS/United States ; UL1 RR024134/RR/NCRR NIH HHS/United States ; }, mesh = {Base Sequence ; Codon ; Contig Mapping ; Gastrointestinal Tract/microbiology/*virology ; *Genetic Variation ; *Genome, Viral ; Humans ; Metagenome ; Models, Genetic ; Molecular Sequence Data ; Mutagenesis ; Open Reading Frames ; RNA, Ribosomal, 16S/metabolism ; Sequence Analysis, DNA ; }, abstract = {Genetic variation is critical in microbial immune evasion and drug resistance, but variation has rarely been studied in complex heterogeneous communities such as the human microbiome. To begin to study natural variation, we analyzed DNA viruses present in the lower gastrointestinal tract of 12 human volunteers by determining 48 billion bases of viral DNA sequence. Viral genomes mostly showed low variation, but 51 loci of ∼100 bp showed extremely high variation, so that up to 96% of the viral genomes encoded unique amino acid sequences. Some hotspots of hypervariation were in genes homologous to the bacteriophage BPP-1 viral tail-fiber gene, which is known to be hypermutagenized by a unique reverse-transcriptase (RT)-based mechanism. Unexpectedly, other hypervariable loci in our data were in previously undescribed gene types, including genes encoding predicted Ig-superfamily proteins. Most of the hypervariable loci were linked to genes encoding RTs of a single clade, which we find is the most abundant clade among gut viruses but only a minor component of bacterial RT populations. Hypervariation was targeted to 5'-AAY-3' asparagine codons, which allows maximal chemical diversification of the encoded amino acids while avoiding formation of stop codons. These findings document widespread targeted hypervariation in the human gut virome, identify previously undescribed types of genes targeted for hypervariation, clarify association with RT gene clades, and motivate studies of hypervariation in the full human microbiome.}, }
@article {pmid22348905, year = {2012}, author = {Ji, YS and Kim, HN and Park, HJ and Lee, JE and Yeo, SY and Yang, JS and Park, SY and Yoon, HS and Cho, GS and Franz, CM and Bomba, A and Shin, HK and Holzapfel, WH}, title = {Modulation of the murine microbiome with a concomitant anti-obesity effect by Lactobacillus rhamnosus GG and Lactobacillus sakei NR28.}, journal = {Beneficial microbes}, volume = {3}, number = {1}, pages = {13-22}, doi = {10.3920/BM2011.0046}, pmid = {22348905}, issn = {1876-2891}, mesh = {Acetyl-CoA Carboxylase/metabolism ; Animals ; Anti-Obesity Agents/administration &amp; dosage/*metabolism ; Bacterial Load ; Biomarkers/analysis ; Fatty Acid Synthases/metabolism ; Feces/microbiology ; Intestine, Small/*microbiology ; Lactobacillus/growth &amp; development/*metabolism ; Liver/metabolism ; Male ; *Metagenome ; Mice ; Mice, Inbred C57BL ; Probiotics/*administration &amp; dosage/metabolism ; RNA, Messenger/metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Stearoyl-CoA Desaturase/metabolism ; }, abstract = {The microbiota of the gastrointestinal tract (GIT) constitutes the major part of the total human microbiome and is considered to be an important regulator of human health and host metabolism. Numerous investigations in recent years have focused on the connection between the human microbiota and metabolic diseases such as obesity, type II diabetes and atherosclerosis. Yet, little is known about the impact of probiotic consumption on the GIT microbial population and the potential effect on chronic diseases. In this study, the modulation of the microbial community in the murine small intestine resulting from probiotic feeding was investigated and was found to be associated with an anti-obesity effect. Changes in the microbiota of the mouse faeces and small intestine were monitored using quantitative real-time PCR and by following the mRNA expression levels of various obesity-related biomarkers following probiotic feeding in a mouse model. Lactobacillus rhamnosus GG and Lactobacillus sakei NR28 (a putative probiotic strain isolated from kimchi) were administered at a daily level of approximately 1×10(8) viable bacteria per mouse (C57BL/6J mice) for up to three weeks. Feeding these strains resulted in a significant reduction of epididymal fat mass, as well as obesity-related biomarkers like acetyl-CoA carboxylase, fatty acid synthase, and stearoyl-CoA desaturase-1 in the liver. The total number and ratio of the microbial groups, i.e. Firmicutes, Bacteroidetes, Clostridium cluster I and XIVab, and Lactobacillus spp. were modulated in the small intestine, and the Firmicutes:Bacteroidetes ratio was decreased. In contrast, no noticeable effect of probiotic feeding could be detected on the faecal microbiota, neither quantitatively, nor with regard to the bacterial groups (Firmicutes, Bacteroidetes, Clostridium cluster I and XIVab, and Lactobacillus spp.) studied.}, }
@article {pmid22279602, year = {2012}, author = {Siqueira, JF and Fouad, AF and Rôças, IN}, title = {Pyrosequencing as a tool for better understanding of human microbiomes.}, journal = {Journal of oral microbiology}, volume = {4}, number = {}, pages = {}, pmid = {22279602}, issn = {2000-2297}, abstract = {Next-generation sequencing technologies have revolutionized the analysis of microbial communities in diverse environments, including the human body. This article reviews several aspects of one of these technologies, the pyrosequencing technique, including its principles, applications, and significant contribution to the study of the human microbiome, with especial emphasis on the oral microbiome. The results brought about by pyrosequencing studies have significantly contributed to refining and augmenting the knowledge of the community membership and structure in and on the human body in healthy and diseased conditions. Because most oral infectious diseases are currently regarded as biofilm-related polymicrobial infections, high-throughput sequencing technologies have the potential to disclose specific patterns related to health or disease. Further advances in technology hold the perspective to have important implications in terms of accurate diagnosis and more effective preventive and therapeutic measures for common oral diseases.}, }
@article {pmid22278670, year = {2012}, author = {Kembel, SW and Jones, E and Kline, J and Northcutt, D and Stenson, J and Womack, AM and Bohannan, BJ and Brown, GZ and Green, JL}, title = {Architectural design influences the diversity and structure of the built environment microbiome.}, journal = {The ISME journal}, volume = {6}, number = {8}, pages = {1469-1479}, pmid = {22278670}, issn = {1751-7370}, mesh = {*Architecture ; Bacteria/classification/genetics ; *Bacterial Physiological Phenomena ; *Biodiversity ; Environmental Microbiology ; Hospitals ; Humidity ; *Metagenome ; Phylogeny ; Temperature ; Ventilation ; }, abstract = {Buildings are complex ecosystems that house trillions of microorganisms interacting with each other, with humans and with their environment. Understanding the ecological and evolutionary processes that determine the diversity and composition of the built environment microbiome--the community of microorganisms that live indoors--is important for understanding the relationship between building design, biodiversity and human health. In this study, we used high-throughput sequencing of the bacterial 16S rRNA gene to quantify relationships between building attributes and airborne bacterial communities at a health-care facility. We quantified airborne bacterial community structure and environmental conditions in patient rooms exposed to mechanical or window ventilation and in outdoor air. The phylogenetic diversity of airborne bacterial communities was lower indoors than outdoors, and mechanically ventilated rooms contained less diverse microbial communities than did window-ventilated rooms. Bacterial communities in indoor environments contained many taxa that are absent or rare outdoors, including taxa closely related to potential human pathogens. Building attributes, specifically the source of ventilation air, airflow rates, relative humidity and temperature, were correlated with the diversity and composition of indoor bacterial communities. The relative abundance of bacteria closely related to human pathogens was higher indoors than outdoors, and higher in rooms with lower airflow rates and lower relative humidity. The observed relationship between building design and airborne bacterial diversity suggests that we can manage indoor environments, altering through building design and operation the community of microbial species that potentially colonize the human microbiome during our time indoors.}, }
@article {pmid22277031, year = {2011}, author = {Bures, J and Kopácová, M and Skodová Fendrichová, M and Rejchrt, S}, title = {[Epidemiology of Helicobacter pylori infection].}, journal = {Vnitrni lekarstvi}, volume = {57}, number = {12}, pages = {993-999}, pmid = {22277031}, issn = {0042-773X}, mesh = {Czech Republic/epidemiology ; Helicobacter Infections/*epidemiology ; *Helicobacter pylori ; Humans ; Prevalence ; Risk Factors ; }, abstract = {Helicobacter pylori (Hp) is the most common chronic bacterial infection in humans worldwide. The prevalence of Hp infection is high in developing countries (80-90%) and lower in developed countries (10-30%). In vast majority of infected individuals, the infection is acquired early in life. The risk of Hp infection is related to low socio-economic status and living conditions at early childhood (density of housing, overcrowding, number of siblings, sharing a bed, and lack of running water, low education of parents). Smoking is a risk factor of Hp infection in adults. In developed countries including the Czech Republic, the overall prevalence of Hp infection has fallen dramatically over recent decades. This decrease can be explained mostly by the relatively favourable and improving socio-economic conditions. However, it is necessary to consider also the fundamental determinants of "modern times" that could cause gradual disappearing of Hp from the human "microbiome".}, }
@article {pmid22240474, year = {2012}, author = {Langille, MG and Meehan, CJ and Beiko, RG}, title = {Human microbiome: a genetic bazaar for microbes?.}, journal = {Current biology : CB}, volume = {22}, number = {1}, pages = {R20-2}, doi = {10.1016/j.cub.2011.11.023}, pmid = {22240474}, issn = {1879-0445}, mesh = {DNA Transposable Elements ; *Gene Transfer, Horizontal ; Humans ; *Metagenome ; }, abstract = {A recent study suggests that lateral gene transfer has been particularly intense among human-associated microbes. What can this tell us about our relationship with our internal microbial world?}, }
@article {pmid22237180, year = {2012}, author = {Baig, S}, title = {Reviewing personal bacteria - the human microbiome project.}, journal = {Journal of the College of Physicians and Surgeons--Pakistan : JCPSP}, volume = {22}, number = {1}, pages = {3-4}, pmid = {22237180}, issn = {1681-7168}, mesh = {Bacteria/*genetics ; Bacterial Infections/*microbiology ; *Biomedical Research ; Female ; Humans ; Male ; *Metagenome ; }, }
@article {pmid22209085, year = {2012}, author = {Rath, CM and Dorrestein, PC}, title = {The bacterial chemical repertoire mediates metabolic exchange within gut microbiomes.}, journal = {Current opinion in microbiology}, volume = {15}, number = {2}, pages = {147-154}, pmid = {22209085}, issn = {1879-0364}, support = {R01 GM094802/GM/NIGMS NIH HHS/United States ; R01 GM086283/GM/NIGMS NIH HHS/United States ; GM094802/GM/NIGMS NIH HHS/United States ; AI095125/AI/NIAID NIH HHS/United States ; R01 AI095125/AI/NIAID NIH HHS/United States ; GM086283/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Bacteria/*chemistry/classification/growth &amp; development/*metabolism ; Gastrointestinal Tract/*microbiology ; Humans ; *Metagenome ; Mice ; *Microbial Interactions ; Phenotype ; }, abstract = {Microbial communities in the gut have been hypothesized to play key roles in the health of the host organism. Exploring the relationship between these populations and disease states has been a focus of the human microbiome project. However, the biological roles of the compounds produced by the gut bacteria are largely unknown. We hypothesize that these compounds act as metabolic exchange factors-mediating inter-species and intra-species interactions in the microbiome. This view is supported through this review of known bacterial metabolic exchange factors and evidence for uncharacterized metabolic exchange factors in the gut. The impact of model systems and technological developments in exploring this hypothesis are also discussed. Together, these investigations are revolutionizing our understanding of the gut microbiome-presenting the possibility of identifying new strategies for treating disease in the host.}, }
@article {pmid23990820, year = {2012}, author = {Collado, MC and Bäuerl, C and Pérez-Martínez, G}, title = {Defining microbiota for developing new probiotics.}, journal = {Microbial ecology in health and disease}, volume = {23}, number = {}, pages = {}, pmid = {23990820}, issn = {0891-060X}, abstract = {The human body harbors complex communities of microbes that play a prominent role in human health. Detailed characterization of the microbiota in the target population forms the basis of probiotic use. Probiotics are defined as live bacterial preparations with clinically documented health effects in humans, and independent of their genus and species, probiotic strains are unique and their beneficial properties on human health have to be assessed in a case-by-case manner. Understanding the mechanisms by which probiotics influence microbiota would facilitate the use of probiotics for both dietary management and reduction in risk of specific diseases. The development of high throughput sequencing methods has allowed metagenomic approaches to study the human microbiome. These efforts are starting to generate an inventory of bacterial taxons and functional features bound to particular health or disease status that allow inferring aspects of the microbiome's function. In the future, this information will allow the rational design of dietary interventions aimed to improve consumer's health via modulation of the microbiota.}, }
@article {pmid23678462, year = {2012}, author = {Eslami, S and Barzgari, Z and Saliani, N and Saeedi, N and Barzegari, A}, title = {Annual fasting; the early calories restriction for cancer prevention.}, journal = {BioImpacts : BI}, volume = {2}, number = {4}, pages = {213-215}, pmid = {23678462}, issn = {2228-5652}, abstract = {Essentially, people's diet and nutritional status has been changed substantially worldwide and several lines of evidence suggest that these changes are to the detriment of their health. Additionally, it has been well documented that unhealthy diet especially the fast foods, untraditional foods or bad-eating-habits influence the human gut microbiome. The gut microbiota shapes immune responses during human life and affects his/her metabolomic profiles. Furthermore, many studies highlight the molecular pathways that mediate host and symbiont interactions that regulate proper immune function and prevention of cancer in the body. Intriguingly, if cancer forms in a human body due to the weakness of immune system in detriment of microbiome, the removal of cancer stem cells can be carried out through early Calories Restriction with Annual Fasting (AF) before tumor development or progress. Besides, fasting can balance the gut microbiome for enhancement of immune system against cancer formation.}, }
@article {pmid22194640, year = {2012}, author = {Markowitz, VM and Chen, IM and Palaniappan, K and Chu, K and Szeto, E and Grechkin, Y and Ratner, A and Jacob, B and Huang, J and Williams, P and Huntemann, M and Anderson, I and Mavromatis, K and Ivanova, NN and Kyrpides, NC}, title = {IMG: the Integrated Microbial Genomes database and comparative analysis system.}, journal = {Nucleic acids research}, volume = {40}, number = {Database issue}, pages = {D115-22}, pmid = {22194640}, issn = {1362-4962}, support = {U01-HG004866/HG/NHGRI NIH HHS/United States ; }, mesh = {*Databases, Genetic ; Eukaryota/genetics ; *Genome, Archaeal ; *Genome, Bacterial ; *Genome, Viral ; *Genomics ; Phenotype ; Plasmids/genetics ; Proteomics ; Software ; Systems Integration ; }, abstract = {The Integrated Microbial Genomes (IMG) system serves as a community resource for comparative analysis of publicly available genomes in a comprehensive integrated context. IMG integrates publicly available draft and complete genomes from all three domains of life with a large number of plasmids and viruses. IMG provides tools and viewers for analyzing and reviewing the annotations of genes and genomes in a comparative context. IMG's data content and analytical capabilities have been continuously extended through regular updates since its first release in March 2005. IMG is available at http://img.jgi.doe.gov. Companion IMG systems provide support for expert review of genome annotations (IMG/ER: http://img.jgi.doe.gov/er), teaching courses and training in microbial genome analysis (IMG/EDU: http://img.jgi.doe.gov/edu) and analysis of genomes related to the Human Microbiome Project (IMG/HMP: http://www.hmpdacc-resources.org/img_hmp).}, }
@article {pmid22193889, year = {2012}, author = {Saxena, D and Li, Y and Yang, L and Pei, Z and Poles, M and Abrams, WR and Malamud, D}, title = {Human microbiome and HIV/AIDS.}, journal = {Current HIV/AIDS reports}, volume = {9}, number = {1}, pages = {44-51}, pmid = {22193889}, issn = {1548-3576}, support = {UH3 CA140233/CA/NCI NIH HHS/United States ; R03-DE019178/DE/NIDCR NIH HHS/United States ; U19-DE018385/DE/NIDCR NIH HHS/United States ; R01-DE020891/DE/NIDCR NIH HHS/United States ; U19 DE018385/DE/NIDCR NIH HHS/United States ; R03 DE019178/DE/NIDCR NIH HHS/United States ; R01 DE020891/DE/NIDCR NIH HHS/United States ; UH2 CA140233/CA/NCI NIH HHS/United States ; UH3CA140233/CA/NCI NIH HHS/United States ; }, mesh = {Female ; Gram-Negative Bacteria ; Gram-Positive Bacteria ; HIV Infections/*microbiology/transmission ; Humans ; Intestines/microbiology ; Lung/microbiology ; Male ; Metagenome/*physiology ; Microbial Interactions/physiology ; Mouth/microbiology ; Penis/microbiology ; Vagina/microbiology ; }, abstract = {Understanding of the human microbiome continues to grow rapidly; however, reports on changes in the microbiome after HIV infection are still limited. This review surveys the progress made in methodology associated with microbiome studies and highlights the remaining challenges to this field. Studies have shown that commensal oral, gut, vaginal, and penile bacteria are vital to the health of the human immune system. Our studies on crosstalk among oral and gastrointestinal soluble innate factors, HIV, and microbes indicated that the oral and gut microbiome was altered in the HIV-positive samples compared to the negative controls. The importance of understanding the bacterial component of HIV/AIDS, and likelihood of "crosstalk" between viral and bacterial pathogens, will help in understanding the role of the microbiome in HIV-infected individuals and facilitate identification of novel antiretroviral factors for use as novel diagnostics, microbicides, or therapeutics against HIV infection.}, }
@article {pmid22184244, year = {2012}, author = {Greenblum, S and Turnbaugh, PJ and Borenstein, E}, title = {Metagenomic systems biology of the human gut microbiome reveals topological shifts associated with obesity and inflammatory bowel disease.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {109}, number = {2}, pages = {594-599}, pmid = {22184244}, issn = {1091-6490}, support = {P50 GM068763/GM/NIGMS NIH HHS/United States ; T32 HG000035/HG/NHGRI NIH HHS/United States ; T32 HG00035/HG/NHGRI NIH HHS/United States ; }, mesh = {Computational Biology ; Databases, Genetic ; Feces/microbiology ; Gastrointestinal Tract/*microbiology ; Humans ; Inflammatory Bowel Diseases/*microbiology ; Metabolic Networks and Pathways/*genetics ; Metagenome/*genetics ; Metagenomics/*methods ; Obesity/*microbiology ; Species Specificity ; Statistics, Nonparametric ; Systems Biology/*methods ; }, abstract = {The human microbiome plays a key role in a wide range of host-related processes and has a profound effect on human health. Comparative analyses of the human microbiome have revealed substantial variation in species and gene composition associated with a variety of disease states but may fall short of providing a comprehensive understanding of the impact of this variation on the community and on the host. Here, we introduce a metagenomic systems biology computational framework, integrating metagenomic data with an in silico systems-level analysis of metabolic networks. Focusing on the gut microbiome, we analyze fecal metagenomic data from 124 unrelated individuals, as well as six monozygotic twin pairs and their mothers, and generate community-level metabolic networks of the microbiome. Placing variations in gene abundance in the context of these networks, we identify both gene-level and network-level topological differences associated with obesity and inflammatory bowel disease (IBD). We show that genes associated with either of these host states tend to be located at the periphery of the metabolic network and are enriched for topologically derived metabolic "inputs." These findings may indicate that lean and obese microbiomes differ primarily in their interface with the host and in the way they interact with host metabolism. We further demonstrate that obese microbiomes are less modular, a hallmark of adaptation to low-diversity environments. We additionally link these topological variations to community species composition. The system-level approach presented here lays the foundation for a unique framework for studying the human microbiome, its organization, and its impact on human health.}, }
@article {pmid22179717, year = {2011}, author = {Kuczynski, J and Lauber, CL and Walters, WA and Parfrey, LW and Clemente, JC and Gevers, D and Knight, R}, title = {Experimental and analytical tools for studying the human microbiome.}, journal = {Nature reviews. Genetics}, volume = {13}, number = {1}, pages = {47-58}, pmid = {22179717}, issn = {1471-0064}, support = {U54HG004969/HG/NHGRI NIH HHS/United States ; R01 MD011389/MD/NIMHD NIH HHS/United States ; T32 GM008759/GM/NIGMS NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; R01 HG004872/HG/NHGRI NIH HHS/United States ; T32 GM142607/GM/NIGMS NIH HHS/United States ; U54 HG004969/HG/NHGRI NIH HHS/United States ; P01 DK078669/DK/NIDDK NIH HHS/United States ; U54 HG003067/HG/NHGRI NIH HHS/United States ; }, mesh = {Algorithms ; Computational Biology/*methods ; DNA/genetics ; DNA Barcoding, Taxonomic/*methods ; Databases, Nucleic Acid ; Genomics/methods ; Humans ; Metagenome/*genetics ; Mouth/microbiology ; Nucleic Acid Amplification Techniques ; RNA, Ribosomal, 16S/*chemistry/genetics ; Skin/microbiology ; Software ; }, abstract = {The human microbiome substantially affects many aspects of human physiology, including metabolism, drug interactions and numerous diseases. This realization, coupled with ever-improving nucleotide sequencing technology, has precipitated the collection of diverse data sets that profile the microbiome. In the past 2 years, studies have begun to include sufficient numbers of subjects to provide the power to associate these microbiome features with clinical states using advanced algorithms, increasing the use of microbiome studies both individually and collectively. Here we discuss tools and strategies for microbiome studies, from primer selection to bioinformatics analysis.}, }
@article {pmid22163302, year = {2011}, author = {Duran-Pinedo, AE and Paster, B and Teles, R and Frias-Lopez, J}, title = {Correlation network analysis applied to complex biofilm communities.}, journal = {PloS one}, volume = {6}, number = {12}, pages = {e28438}, pmid = {22163302}, issn = {1932-6203}, mesh = {Algorithms ; Bacteroides/genetics ; Bayes Theorem ; *Biofilms ; DNA/genetics ; Dental Plaque/microbiology ; Hot Temperature ; Humans ; *Metagenome ; Models, Biological ; Models, Genetic ; Models, Theoretical ; Nucleic Acid Hybridization ; Oligonucleotide Array Sequence Analysis ; Periodontitis/genetics ; Principal Component Analysis ; Systems Biology ; }, abstract = {The complexity of the human microbiome makes it difficult to reveal organizational principles of the community and even more challenging to generate testable hypotheses. It has been suggested that in the gut microbiome species such as Bacteroides thetaiotaomicron are keystone in maintaining the stability and functional adaptability of the microbial community. In this study, we investigate the interspecies associations in a complex microbial biofilm applying systems biology principles. Using correlation network analysis we identified bacterial modules that represent important microbial associations within the oral community. We used dental plaque as a model community because of its high diversity and the well known species-species interactions that are common in the oral biofilm. We analyzed samples from healthy individuals as well as from patients with periodontitis, a polymicrobial disease. Using results obtained by checkerboard hybridization on cultivable bacteria we identified modules that correlated well with microbial complexes previously described. Furthermore, we extended our analysis using the Human Oral Microbe Identification Microarray (HOMIM), which includes a large number of bacterial species, among them uncultivated organisms present in the mouth. Two distinct microbial communities appeared in healthy individuals while there was one major type in disease. Bacterial modules in all communities did not overlap, indicating that bacteria were able to effectively re-associate with new partners depending on the environmental conditions. We then identified hubs that could act as keystone species in the bacterial modules. Based on those results we then cultured a not-yet-cultivated microorganism, Tannerella sp. OT286 (clone BU063). After two rounds of enrichment by a selected helper (Prevotella oris OT311) we obtained colonies of Tannerella sp. OT286 growing on blood agar plates. This system-level approach would open the possibility of manipulating microbial communities in a targeted fashion as well as associating certain bacterial modules to clinical traits (e.g.: obesity, Crohn's disease, periodontal disease, etc).}, }
@article {pmid22157439, year = {2012}, author = {Sibony, M and Jones, NL}, title = {Recent advances in Helicobacter pylori pathogenesis.}, journal = {Current opinion in gastroenterology}, volume = {28}, number = {1}, pages = {30-35}, doi = {10.1097/MOG.0b013e32834dda51}, pmid = {22157439}, issn = {1531-7056}, support = {//Canadian Institutes of Health Research/Canada ; }, mesh = {Animals ; Anti-Bacterial Agents/*therapeutic use ; Gastric Mucosa/*microbiology ; Global Health ; *Helicobacter Infections/drug therapy/epidemiology/microbiology ; Helicobacter pylori/*pathogenicity ; Humans ; Incidence ; *Stomach Diseases/drug therapy/epidemiology/microbiology ; }, abstract = {PURPOSE OF REVIEW: Helicobacter pylori is implicated in numerous gastric pathologies; however, the prevalence of infection is declining in developed countries. Therefore, it is important to understand the complex mechanism of its interaction with the host and how the changing epidemiology of infection may impact on disease. In this review, we systemically revisit the major novel discoveries of the last year relating to H. pylori disease pathogenesis.<br><br>RECENT FINDINGS: Novel pathways have been implicated in H. pylori cytotoxin-associated gene (CagA) mediated carcinogenesis, highlighting the aberrant regulation of proliferation and apoptosis. Furthermore, the human microbiome was implicated as having a key role in H. pylori-related disease development. Several studies have begun to delineate the mechanisms behind the epidemiologically inverse correlation of H. pylori infection with asthma and inflammatory bowel disease.<br><br>SUMMARY: The recent findings enable researchers to focus on novel and previously unsuspected mechanisms in the development of disease, and prompt further research into possible therapeutic approaches. The potential beneficial aspects of H. pylori colonization and the role bacterial flora play in promoting disease have yet to be elucidated, but promise to have a great impact on patient care.}, }
@article {pmid22157322, year = {2012}, author = {Tosh, PK and McDonald, LC}, title = {Infection control in the multidrug-resistant era: tending the human microbiome.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {54}, number = {5}, pages = {707-713}, doi = {10.1093/cid/cir899}, pmid = {22157322}, issn = {1537-6591}, mesh = {Animals ; Antibiosis ; *Drug Resistance, Multiple ; Humans ; *Infection Control ; Metagenome/*physiology ; Public Health ; Translational Research, Biomedical ; }, abstract = {Increasing understanding of the normal commensal microorganisms in humans suggests that restoring and maintaining the microbiome may provide a key to preventing colonization and infection with multidrug-resistant organisms (MDROs). Intact communities of commensals can prevent colonization with MDROs through both competition for space and resources and the complex immunologic and biochemical interactions that have developed between commensal and host over millennia. Current antimicrobials, however, exert tremendous collateral damage to the human microbiome through overuse and broadening spectrum, which has likely been the driving force behind the introduction and proliferation of MDROs. The future direction of infection control and anti-infective therapy will likely capitalize on an expanding understanding of the protective role of the microbiome by (1) developing and using more microbiome-sparing antimicrobial therapy, (2) developing techniques to maintain and restore indigenous microbiota, and (3) discovering and exploiting host protective mechanisms normally afforded by an intact microbiome.}, }
@article {pmid22137452, year = {2012}, author = {Rauch, M and Lynch, SV}, title = {The potential for probiotic manipulation of the gastrointestinal microbiome.}, journal = {Current opinion in biotechnology}, volume = {23}, number = {2}, pages = {192-201}, doi = {10.1016/j.copbio.2011.11.004}, pmid = {22137452}, issn = {1879-0429}, mesh = {Animals ; Gastrointestinal Tract/*immunology/*microbiology ; Humans ; Immune System/*microbiology ; *Metagenome ; Probiotics/*administration &amp; dosage/classification ; }, abstract = {Multiple internal and external sites of the healthy human body are colonized by a diversity of symbiotic microbes. The microbial assemblages found in the intestine represent some of the most dense and diverse of these human-associated ecosystems. Unsurprisingly, the enteric microbiome, that is the totality of microbes, their combined genomes, and their interactions with the human body, has a profound impact on physiological aspects of mammalian function, not least, host immune response. Lack of early-life exposure to certain microbes, or shifts in the composition of the gastrointestinal microbiome have been linked to the development and progression of several intestinal and extra-intestinal diseases, including childhood asthma development and inflammatory bowel disease. Modulating microbial exposure through probiotic supplementation represents a long-held strategy towards ameliorating disease via intestinal microbial community restructuring. This field has experienced somewhat of a resurgence over the past few years, primarily due to the exponential increase in human microbiome studies and a growing appreciation of our dependence on resident microbiota to modulate human health. This review aims to review recent regulatory aspects related to probiotics in food. It also summarizes what is known to date with respect to human gastrointestinal microbiota - the niche which has been most extensively studied in the human system - and the evidence for probiotic supplementation as a viable therapeutic strategy for modulating this consortium.}, }
@article {pmid22134646, year = {2012}, author = {McDonald, D and Price, MN and Goodrich, J and Nawrocki, EP and DeSantis, TZ and Probst, A and Andersen, GL and Knight, R and Hugenholtz, P}, title = {An improved Greengenes taxonomy with explicit ranks for ecological and evolutionary analyses of bacteria and archaea.}, journal = {The ISME journal}, volume = {6}, number = {3}, pages = {610-618}, pmid = {22134646}, issn = {1751-7370}, support = {UH2/UH3CA140233/CA/NCI NIH HHS/United States ; U01 HG004866/HG/NHGRI NIH HHS/United States ; R01 HG004872/HG/NHGRI NIH HHS/United States ; U01-HG004866/HG/NHGRI NIH HHS/United States ; /HHMI_/Howard Hughes Medical Institute/United States ; }, mesh = {Archaea/*classification/genetics ; Bacteria/*classification/genetics ; Classification/*methods ; *Databases, Genetic ; Metagenomics ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Software ; }, abstract = {Reference phylogenies are crucial for providing a taxonomic framework for interpretation of marker gene and metagenomic surveys, which continue to reveal novel species at a remarkable rate. Greengenes is a dedicated full-length 16S rRNA gene database that provides users with a curated taxonomy based on de novo tree inference. We developed a 'taxonomy to tree' approach for transferring group names from an existing taxonomy to a tree topology, and used it to apply the Greengenes, National Center for Biotechnology Information (NCBI) and cyanoDB (Cyanobacteria only) taxonomies to a de novo tree comprising 408,315 sequences. We also incorporated explicit rank information provided by the NCBI taxonomy to group names (by prefixing rank designations) for better user orientation and classification consistency. The resulting merged taxonomy improved the classification of 75% of the sequences by one or more ranks relative to the original NCBI taxonomy with the most pronounced improvements occurring in under-classified environmental sequences. We also assessed candidate phyla (divisions) currently defined by NCBI and present recommendations for consolidation of 34 redundantly named groups. All intermediate results from the pipeline, which includes tree inference, jackknifing and transfer of a donor taxonomy to a recipient tree (tax2tree) are available for download. The improved Greengenes taxonomy should provide important infrastructure for a wide range of megasequencing projects studying ecosystems on scales ranging from our own bodies (the Human Microbiome Project) to the entire planet (the Earth Microbiome Project). The implementation of the software can be obtained from http://sourceforge.net/projects/tax2tree/.}, }
@article {pmid22112388, year = {2012}, author = {Lewis, CM and Obregón-Tito, A and Tito, RY and Foster, MW and Spicer, PG}, title = {The Human Microbiome Project: lessons from human genomics.}, journal = {Trends in microbiology}, volume = {20}, number = {1}, pages = {1-4}, pmid = {22112388}, issn = {1878-4380}, support = {R01 GM089886/GM/NIGMS NIH HHS/United States ; R01 HG005172/HG/NHGRI NIH HHS/United States ; R01 HG005172-01/HG/NHGRI NIH HHS/United States ; R01 GM089886-01A1/GM/NIGMS NIH HHS/United States ; }, mesh = {Genomics/*methods/trends ; Humans ; Medicine/methods/trends ; *Metagenome ; }, abstract = {The Human Microbiome Project (HMP) is following in the footsteps of the Human Genome Project (HGP), which will include exciting discoveries, but also potential disappointment and resentment over the lack of medical applications. There is a wiser path for the HMP. This path includes a greater attention to rare variation, an early commitment to an ethical inclusion of indigenous communities, and a recruitment strategy in which medical benefits are de-emphasized.}, }
@article {pmid22039404, year = {2011}, author = {Belda-Ferre, P and Cabrera-Rubio, R and Moya, A and Mira, A}, title = {Mining virulence genes using metagenomics.}, journal = {PloS one}, volume = {6}, number = {10}, pages = {e24975}, pmid = {22039404}, issn = {1932-6203}, mesh = {Bacteria/genetics/*pathogenicity ; Genome, Bacterial ; *Metagenomics ; Virulence/*genetics ; }, abstract = {When a bacterial genome is compared to the metagenome of an environment it inhabits, most genes recruit at high sequence identity. In free-living bacteria (for instance marine bacteria compared against the ocean metagenome) certain genomic regions are totally absent in recruitment plots, representing therefore genes unique to individual bacterial isolates. We show that these Metagenomic Islands (MIs) are also visible in bacteria living in human hosts when their genomes are compared to sequences from the human microbiome, despite the compartmentalized structure of human-related environments such as the gut. From an applied point of view, MIs of human pathogens (e.g. those identified in enterohaemorragic Escherichia coli against the gut metagenome or in pathogenic Neisseria meningitidis against the oral metagenome) include virulence genes that appear to be absent in related strains or species present in the microbiome of healthy individuals. We propose that this strategy (i.e. recruitment analysis of pathogenic bacteria against the metagenome of healthy subjects) can be used to detect pathogenicity regions in species where the genes involved in virulence are poorly characterized. Using this approach, we detect well-known pathogenicity islands and identify new potential virulence genes in several human pathogens.}, }
@article {pmid22037308, year = {2011}, author = {Smillie, CS and Smith, MB and Friedman, J and Cordero, OX and David, LA and Alm, EJ}, title = {Ecology drives a global network of gene exchange connecting the human microbiome.}, journal = {Nature}, volume = {480}, number = {7376}, pages = {241-244}, pmid = {22037308}, issn = {1476-4687}, support = {T32 GM087237/GM/NIGMS NIH HHS/United States ; }, mesh = {Bacteria/*genetics/isolation &amp; purification/metabolism/pathogenicity ; *Biological Evolution ; Drug Resistance, Microbial/genetics ; *Ecosystem ; Gene Transfer, Horizontal/*genetics ; Genes, Bacterial/genetics ; Genome, Bacterial/genetics ; Humans ; Metagenome/*genetics ; Organ Specificity ; Phylogeny ; Phylogeography ; RNA, Ribosomal, 16S/genetics ; }, abstract = {Horizontal gene transfer (HGT), the acquisition of genetic material from non-parental lineages, is known to be important in bacterial evolution. In particular, HGT provides rapid access to genetic innovations, allowing traits such as virulence, antibiotic resistance and xenobiotic metabolism to spread through the human microbiome. Recent anecdotal studies providing snapshots of active gene flow on the human body have highlighted the need to determine the frequency of such recent transfers and the forces that govern these events. Here we report the discovery and characterization of a vast, human-associated network of gene exchange, large enough to directly compare the principal forces shaping HGT. We show that this network of 10,770 unique, recently transferred (more than 99% nucleotide identity) genes found in 2,235 full bacterial genomes, is shaped principally by ecology rather than geography or phylogeny, with most gene exchange occurring between isolates from ecologically similar, but geographically separated, environments. For example, we observe 25-fold more HGT between human-associated bacteria than among ecologically diverse non-human isolates (P = 3.0 × 10(-270)). We show that within the human microbiome this ecological architecture continues across multiple spatial scales, functional classes and ecological niches with transfer further enriched among bacteria that inhabit the same body site, have the same oxygen tolerance or have the same ability to cause disease. This structure offers a window into the molecular traits that define ecological niches, insight that we use to uncover sources of antibiotic resistance and identify genes associated with the pathology of meningitis and other diseases.}, }
@article {pmid21726221, year = {2011}, author = {Peterson, SN and Snesrud, E and Schork, NJ and Bretz, WA}, title = {Dental caries pathogenicity: a genomic and metagenomic perspective.}, journal = {International dental journal}, volume = {61 Suppl 1}, number = {Suppl 1}, pages = {11-22}, pmid = {21726221}, issn = {0020-6539}, support = {R01 DE015351/DE/NIDCR NIH HHS/United States ; }, mesh = {Animals ; *Biofilms ; Dental Caries/*genetics/*microbiology ; Dental Plaque/genetics/microbiology ; Gene Expression Profiling ; *Gene Expression Regulation, Bacterial ; *Genomics ; Glycolysis ; Humans ; Metagenome ; Microbial Interactions ; Streptococcus mutans/genetics/metabolism ; }, abstract = {In this review we address the subject of dental caries pathogenicity from a genomic and metagenomic perspective. The application of genomic technologies is certain to yield novel insights into the relationship between the bacterial flora, dental health and disease. Three primary attributes of bacterial species are thought to have direct impact on caries development, these include: adherence on tooth surfaces (biofilm formation), acid production and acid tolerance. Attempts to define the specific aetiological agents of dental caries have proven to be elusive, supporting the notion that caries aetiology is perhaps complex and multi-faceted. The recently introduced Human Microbiome Project (HMP) that endeavors to characterise the micro-organisms living in and on the human body is likely to shed new light on these questions and improve our understanding of polymicrobial disease, microbial ecology in the oral cavity and provide new avenues for therapeutic and molecular diagnostics developments.}, }
@article {pmid22018233, year = {2011}, author = {Plottel, CS and Blaser, MJ}, title = {Microbiome and malignancy.}, journal = {Cell host &amp; microbe}, volume = {10}, number = {4}, pages = {324-335}, pmid = {22018233}, issn = {1934-6069}, support = {R01 DK090989-02/DK/NIDDK NIH HHS/United States ; 5 P30 CA016087/CA/NCI NIH HHS/United States ; P30 CA016087/CA/NCI NIH HHS/United States ; 1UL1RR029893/RR/NCRR NIH HHS/United States ; R01 GM063270/GM/NIGMS NIH HHS/United States ; R01DK090989/DK/NIDDK NIH HHS/United States ; R01GM63270/GM/NIGMS NIH HHS/United States ; UH2 AR057506-01S2/AR/NIAMS NIH HHS/United States ; R01 GM063270-11/GM/NIGMS NIH HHS/United States ; R01 DK090989/DK/NIDDK NIH HHS/United States ; P30 CA016087-31/CA/NCI NIH HHS/United States ; UL1 RR029893-03/RR/NCRR NIH HHS/United States ; UL1 RR029893/RR/NCRR NIH HHS/United States ; UH2 AR057506/AR/NIAMS NIH HHS/United States ; }, mesh = {Archaea/*growth &amp; development/metabolism ; Bacteria/*growth &amp; development/metabolism ; Carcinogens/metabolism ; Eukaryota/*growth &amp; development/metabolism ; Humans ; *Metagenome ; Microbial Interactions ; Models, Biological ; Neoplasms/*epidemiology/*etiology ; }, abstract = {Current knowledge is insufficient to explain why only a proportion of individuals exposed to environmental carcinogens or carrying a genetic predisposition to cancer develop disease. Clearly, other factors must be important, and one such element that has recently received attention is the human microbiome, the residential microbes including Bacteria, Archaea, Eukaryotes, and viruses that colonize humans. Here, we review principles and paradigms of microbiome-related malignancy, as illustrated by three specific microbial-host interactions. We review the effects of the microbiota on local and adjacent neoplasia, present the estrobolome model of distant effects, and discuss the complex interactions with a latent virus leading to malignancy. These are separate facets of a complex biology interfacing all the microbial species we harbor from birth onward toward early reproductive success and eventual senescence.}, }
@article {pmid22018227, year = {2011}, author = {Proctor, LM}, title = {The Human Microbiome Project in 2011 and beyond.}, journal = {Cell host &amp; microbe}, volume = {10}, number = {4}, pages = {287-291}, doi = {10.1016/j.chom.2011.10.001}, pmid = {22018227}, issn = {1934-6069}, mesh = {*Biodiversity ; Humans ; *Metagenome ; }, abstract = {The human microbiome comprises the genes and genomes of the microbiota that inhabit the body. We highlight Human Microbiome Project (HMP) resources, including 600 microbial reference genomes, 70 million 16S sequences, 700 metagenomes, and 60 million predicted genes from healthy adult microbiomes. Microbiome studies of specific diseases and future research directions are also discussed.}, }
@article {pmid21984758, year = {2011}, author = {Liu, Z and Hsiao, W and Cantarel, BL and Drábek, EF and Fraser-Liggett, C}, title = {Sparse distance-based learning for simultaneous multiclass classification and feature selection of metagenomic data.}, journal = {Bioinformatics (Oxford, England)}, volume = {27}, number = {23}, pages = {3242-3249}, pmid = {21984758}, issn = {1367-4811}, support = {1R03CA133899-01A210/CA/NCI NIH HHS/United States ; 1UH2DK083982-01/DK/NIDDK NIH HHS/United States ; 4UH3DK083991-02/DK/NIDDK NIH HHS/United States ; }, mesh = {Algorithms ; *Artificial Intelligence ; Bacteria/*classification ; Humans ; Metagenome ; Metagenomics/*methods ; Sample Size ; Skin/microbiology ; }, abstract = {MOTIVATION: Direct sequencing of microbes in human ecosystems (the human microbiome) has complemented single genome cultivation and sequencing to understand and explore the impact of commensal microbes on human health. As sequencing technologies improve and costs decline, the sophistication of data has outgrown available computational methods. While several existing machine learning methods have been adapted for analyzing microbiome data recently, there is not yet an efficient and dedicated algorithm available for multiclass classification of human microbiota.<br><br>RESULTS: By combining instance-based and model-based learning, we propose a novel sparse distance-based learning method for simultaneous class prediction and feature (variable or taxa, which is used interchangeably) selection from multiple treatment populations on the basis of 16S rRNA sequence count data. Our proposed method simultaneously minimizes the intraclass distance and maximizes the interclass distance with many fewer estimated parameters than other methods. It is very efficient for problems with small sample sizes and unbalanced classes, which are common in metagenomic studies. We implemented this method in a MATLAB toolbox called MetaDistance. We also propose several approaches for data normalization and variance stabilization transformation in MetaDistance. We validate this method on several real and simulated 16S rRNA datasets to show that it outperforms existing methods for classifying metagenomic data. This article is the first to address simultaneous multifeature selection and class prediction with metagenomic count data.<br><br>AVAILABILITY: The MATLAB toolbox is freely available online at http://metadistance.igs.umaryland.edu/.<br><br>CONTACT: zliu@umm.edu<br><br>SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.}, }
@article {pmid21982589, year = {2011}, author = {Hawkins, AK and O'Doherty, KC}, title = {"Who owns your poop?": insights regarding the intersection of human microbiome research and the ELSI aspects of biobanking and related studies.}, journal = {BMC medical genomics}, volume = {4}, number = {}, pages = {72}, pmid = {21982589}, issn = {1755-8794}, support = {94314/CAPMC/CIHR/Canada ; 193095/CAPMC/CIHR/Canada ; }, mesh = {*Biological Specimen Banks/economics/ethics/legislation &amp; jurisprudence ; Consent Forms/economics/ethics/legislation &amp; jurisprudence ; Ethics, Research ; Humans ; Interviews as Topic ; *Metagenome ; Ownership/economics/ethics/legislation &amp; jurisprudence ; Privacy/legislation &amp; jurisprudence ; Research/economics/legislation &amp; jurisprudence ; }, abstract = {BACKGROUND: While the social, ethical, and legal implications of biobanking and large scale data sharing are already complicated enough, they may be further compounded by research on the human microbiome.<br><br>DISCUSSION: The human microbiome is the entire complement of microorganisms that exists in and on every human body. Currently most biobanks focus primarily on human tissues and/or associated data (e.g. health records). Accordingly, most discussions in the social sciences and humanities on these issues are focused (appropriately so) on the implications of biobanks and sharing data derived from human tissues. However, rapid advances in human microbiome research involve collecting large amounts of data on microorganisms that exist in symbiotic relationships with the human body. Currently it is not clear whether these microorganisms should be considered part of or separate from the human body. Arguments can be made for both, but ultimately it seems that the dichotomy of human versus non-human and self versus non-self inevitably breaks down in this context. This situation has the potential to add further complications to debates on biobanking.<br><br>SUMMARY: In this paper, we revisit some of the core problem areas of privacy, consent, ownership, return of results, governance, and benefit sharing, and consider how they might be impacted upon by human microbiome research. Some of the issues discussed also have relevance to other forms of microbial research. Discussion of these themes is guided by conceptual analysis of microbiome research and interviews with leading Canadian scientists in the field.}, }
@article {pmid21936031, year = {2012}, author = {Nagalingam, NA and Lynch, SV}, title = {Role of the microbiota in inflammatory bowel diseases.}, journal = {Inflammatory bowel diseases}, volume = {18}, number = {5}, pages = {968-984}, doi = {10.1002/ibd.21866}, pmid = {21936031}, issn = {1536-4844}, mesh = {Humans ; Inflammatory Bowel Diseases/classification/*genetics/*microbiology ; Metagenome/*physiology ; }, abstract = {Studying the role of the human microbiome as it relates to human health status has revolutionized our view of microbial community contributions to a large number of diseases, particularly chronic inflammatory disorders. The lower gastrointestinal (GI) tract houses trillions of microbial cells representing a large diversity of species in relatively well-defined phylogenetic ratios that are associated with maintenance of key aspects of host physiology and immune homeostasis. It is not surprising, therefore, that many GI inflammatory diseases, including inflammatory bowel disease (IBD), are associated with substantial changes in the composition of these microbial assemblages, either as a cause or consequence of host inflammatory response. Here we review current knowledge in the emerging field of human microbiome research as it relates to IBD, specifically focusing on Crohn's disease (CD) and ulcerative colitis (UC). We discuss bacteriotherapeutic efforts to restore GI microbial assemblage integrity via probiotic supplementation of IBD patients, and speculate on future directions for the field.}, }
@article {pmid21931163, year = {2011}, author = {Bruel, L and Sulzenbacher, G and Cervera Tison, M and Pujol, A and Nicoletti, C and Perrier, J and Galinier, A and Ropartz, D and Fons, M and Pompeo, F and Giardina, T}, title = {α-Galactosidase/sucrose kinase (AgaSK), a novel bifunctional enzyme from the human microbiome coupling galactosidase and kinase activities.}, journal = {The Journal of biological chemistry}, volume = {286}, number = {47}, pages = {40814-40823}, pmid = {21931163}, issn = {1083-351X}, mesh = {Anaerobiosis ; Animals ; Catalytic Domain ; Crystallography, X-Ray ; Humans ; Intestines/microbiology ; *Metagenome ; Models, Molecular ; Molecular Sequence Data ; Phosphotransferases (Alcohol Group Acceptor)/chemistry/*metabolism ; Protein Multimerization ; Protein Structure, Quaternary ; Raffinose/metabolism ; Rats ; Ruminococcus/*enzymology ; Substrate Specificity ; Sucrose/*metabolism ; alpha-Galactosidase/chemistry/*metabolism ; }, abstract = {α-Galactosides are non-digestible carbohydrates widely distributed in plants. They are a potential source of energy in our daily food, and their assimilation by microbiota may play a role in obesity. In the intestinal tract, they are degraded by microbial glycosidases, which are often modular enzymes with catalytic domains linked to carbohydrate-binding modules. Here we introduce a bifunctional enzyme from the human intestinal bacterium Ruminococcus gnavus E1, α-galactosidase/sucrose kinase (AgaSK). Sequence analysis showed that AgaSK is composed of two domains: one closely related to α-galactosidases from glycoside hydrolase family GH36 and the other containing a nucleotide-binding motif. Its biochemical characterization showed that AgaSK is able to hydrolyze melibiose and raffinose to galactose and either glucose or sucrose, respectively, and to specifically phosphorylate sucrose on the C6 position of glucose in the presence of ATP. The production of sucrose-6-P directly from raffinose points toward a glycolytic pathway in bacteria, not described so far. The crystal structures of the galactosidase domain in the apo form and in complex with the product shed light onto the reaction and substrate recognition mechanisms and highlight an oligomeric state necessary for efficient substrate binding and suggesting a cross-talk between the galactose and kinase domains.}, }
@article {pmid21924962, year = {2011}, author = {Legato, MJ}, title = {Worlds within worlds: the human microbiome.}, journal = {Gender medicine}, volume = {8}, number = {5}, pages = {339-341}, doi = {10.1016/j.genm.2011.08.033}, pmid = {21924962}, issn = {1878-7398}, mesh = {Humans ; *Metagenome ; Sex Factors ; }, }
@article {pmid21910623, year = {2012}, author = {Pflughoeft, KJ and Versalovic, J}, title = {Human microbiome in health and disease.}, journal = {Annual review of pathology}, volume = {7}, number = {}, pages = {99-122}, doi = {10.1146/annurev-pathol-011811-132421}, pmid = {21910623}, issn = {1553-4014}, mesh = {Animals ; Disease/*etiology ; Disease Susceptibility ; Gene Transfer, Horizontal ; Humans ; *Metagenome ; Metagenomics ; Microbial Interactions ; Sequence Analysis, DNA/methods ; Systems Biology ; }, abstract = {Mammals are complex assemblages of mammalian and bacterial cells organized into functional organs, tissues, and cellular communities. Human biology can no longer concern itself only with human cells: Microbiomes at different body sites and functional metagenomics must be considered part of systems biology. The emergence of metagenomics has resulted in the generation of vast data sets of microbial genes and pathways present in different body habitats. The profound differences between microbiomes in various body sites reveal how metagenomes contribute to tissue and organ function. As next-generation DNA-sequencing methods provide whole-metagenome data in addition to gene-expression profiling, metaproteomics, and metabonomics, differences in microbial composition and function are being linked to health and disease states in different organs and tissues. Global parameters of microbial communities may provide valuable information regarding human health status and disease predisposition. More detailed knowledge of the human microbiome will yield next-generation diagnostics and therapeutics for various acute, chronic, localized, and systemic human diseases.}, }
@article {pmid21812894, year = {2012}, author = {Kootte, RS and Vrieze, A and Holleman, F and Dallinga-Thie, GM and Zoetendal, EG and de Vos, WM and Groen, AK and Hoekstra, JB and Stroes, ES and Nieuwdorp, M}, title = {The therapeutic potential of manipulating gut microbiota in obesity and type 2 diabetes mellitus.}, journal = {Diabetes, obesity &amp; metabolism}, volume = {14}, number = {2}, pages = {112-120}, doi = {10.1111/j.1463-1326.2011.01483.x}, pmid = {21812894}, issn = {1463-1326}, mesh = {Animals ; Anti-Bacterial Agents/therapeutic use ; Bariatric Surgery ; Bile Acids and Salts/*metabolism ; Diabetes Mellitus, Type 2/metabolism/*microbiology/physiopathology ; Diet ; Fatty Acids, Volatile/*metabolism ; Gastrointestinal Tract/metabolism/*microbiology/physiopathology ; Humans ; *Metagenome ; Mice ; Obesity/metabolism/*microbiology/physiopathology ; Prebiotics ; Probiotics/therapeutic use ; }, abstract = {Obesity and type 2 diabetes mellitus (T2DM) are attributed to a combination of genetic susceptibility and lifestyle factors. Their increasing prevalence necessitates further studies on modifiable causative factors and novel treatment options. The gut microbiota has emerged as an important contributor to the obesity--and T2DM--epidemic proposed to act by increasing energy harvest from the diet. Although obesity is associated with substantial changes in the composition and metabolic function of the gut microbiota, the pathophysiological processes remain only partly understood. In this review we will describe the development of the adult human microbiome and discuss how the composition of the gut microbiota changes in response to modulating factors. The influence of short-chain fatty acids, bile acids, prebiotics, probiotics, antibiotics and microbial transplantation is discussed from studies using animal and human models. Ultimately, we aim to translate these findings into therapeutic pathways for obesity and T2DM in humans.}, }
@article {pmid21808643, year = {2011}, author = {Yoon, SS and Sun, J}, title = {Probiotics, nuclear receptor signaling, and anti-inflammatory pathways.}, journal = {Gastroenterology research and practice}, volume = {2011}, number = {}, pages = {971938}, pmid = {21808643}, issn = {1687-630X}, support = {K01 DK075386/DK/NIDDK NIH HHS/United States ; R03 DK089010/DK/NIDDK NIH HHS/United States ; }, abstract = {There is increased investigation of the human microbiome as it relates to health and disease. Dysbiosis is implicated in various clinical conditions including inflammatory bowel disease (IBD). Probiotics have been explored as a potential treatment for IBD and other diseases. The mechanism of action for probiotics has yet to be fully elucidated. This paper discusses novel mechanisms of action for probiotics involving anti-inflammatory signaling pathways. We highlight recent progress in probiotics and nuclear receptor signaling, such as peroxisome-proliferator-activated receptor gamma (PPARγ) and vitamin D receptor (VDR). We also discuss future areas of investigation.}, }
@article {pmid21808637, year = {2011}, author = {Parfrey, LW and Walters, WA and Knight, R}, title = {Microbial eukaryotes in the human microbiome: ecology, evolution, and future directions.}, journal = {Frontiers in microbiology}, volume = {2}, number = {}, pages = {153}, pmid = {21808637}, issn = {1664-302X}, support = {T32 GM008759/GM/NIGMS NIH HHS/United States ; T32 GM142607/GM/NIGMS NIH HHS/United States ; }, abstract = {High throughput sequencing technology has opened a window into the vast communities of bacteria that live on and in humans, demonstrating tremendous variability, and that they play a large role in health and disease. The eukaryotic component of the human gut microbiome remains relatively unexplored with these methods, but turning these tools toward microbial eukaryotes in the gut will likely yield myriad insights into disease as well as the ecological and evolutionary principles that govern the gut microbiota. Microbial eukaryotes are common inhabitants of the human gut worldwide and parasitic taxa are a major source of morbidity and mortality, especially in developing countries, though there are also taxa that cause no harm or are beneficial. While the role microbial eukaryotes play in healthy individuals is much less clear, there are likely many complex interactions between the bacterial, archaeal, and eukaryotic microbiota that influence human health. Integrating eukaryotic microbes into a broad view of microbiome function requires an integrated ecological approach rather than one focused on specific, disease-causing taxa. Moving forward, we expect broad surveys of the eukaryotic microbiota and associated bacteria from geographically and socioeconomically diverse populations to paint a more complete picture of the human gut microbiome in health and disease.}, }
@article {pmid21802347, year = {2011}, author = {Sommer, MO and Dantas, G}, title = {Antibiotics and the resistant microbiome.}, journal = {Current opinion in microbiology}, volume = {14}, number = {5}, pages = {556-563}, doi = {10.1016/j.mib.2011.07.005}, pmid = {21802347}, issn = {1879-0364}, mesh = {Anti-Bacterial Agents/*pharmacology ; Bacteria/*drug effects ; *Drug Resistance, Bacterial ; Evolution, Molecular ; Humans ; Metagenome/*drug effects ; Selection, Genetic ; }, abstract = {Since the discovery and clinical application of antibiotics, pathogens and the human microbiota have faced a near continuous exposure to these selective agents. A well-established consequence of this exposure is the evolution of multidrug-resistant pathogens, which can become virtually untreatable. Less appreciated are the concomitant changes in the human microbiome in response to these assaults and their contribution to clinical resistance problems. Studies have shown that pervasive changes to the human microbiota result from antibiotic treatment and that resistant strains can persist for years. Additionally, culture-independent functional characterization of the resistance genes from the microbiome has demonstrated a close evolutionary relationship between resistance genes in the microbiome and in pathogens. Application of these techniques and novel cultivation methods are expected to significantly expand our understanding of the interplay between antibiotics and the microbiome.}, }
@article {pmid21782228, year = {2011}, author = {Bisgaard, H and Li, N and Bonnelykke, K and Chawes, BL and Skov, T and Paludan-Müller, G and Stokholm, J and Smith, B and Krogfelt, KA}, title = {Reduced diversity of the intestinal microbiota during infancy is associated with increased risk of allergic disease at school age.}, journal = {The Journal of allergy and clinical immunology}, volume = {128}, number = {3}, pages = {646-52.e1-5}, doi = {10.1016/j.jaci.2011.04.060}, pmid = {21782228}, issn = {1097-6825}, mesh = {Bacteria/*classification/genetics/isolation &amp; purification ; Child ; Cohort Studies ; DNA, Bacterial/analysis ; Denaturing Gradient Gel Electrophoresis ; Eosinophilia/diagnosis/epidemiology ; Feces/microbiology ; Humans ; Hypersensitivity, Immediate/diagnosis/*epidemiology ; Immunoglobulin E/blood ; Infant ; Infant, Newborn ; Intestines/*microbiology ; *Metagenome ; Polymerase Chain Reaction ; RNA, Ribosomal, 16S/genetics ; Rhinitis/diagnosis/epidemiology ; Risk ; Skin Tests ; }, abstract = {BACKGROUND: Changes in the human microbiome have been suggested as a risk factor for a number of lifestyle-related disorders, such as atopic diseases, possibly through a modifying influence on immune maturation in infancy.<br><br>OBJECTIVES: We aimed to explore the association between neonatal fecal flora and the development of atopic disorders until age 6 years, hypothesizing that the diversity of the intestinal microbiota influences disease development.<br><br>METHODS: We studied the intestinal microbiota in infants in the Copenhagen Prospective Study on Asthma in Childhood, a clinical study of a birth cohort of 411 high-risk children followed for 6 years by clinical assessments at 6-month intervals, as well as at acute symptom exacerbations. Bacterial flora was analyzed at 1 and 12 months of age by using molecular techniques based on 16S rRNA PCR combined with denaturing gradient gel electrophoresis, as well as conventional culturing. The main outcome measures were the development of allergic sensitization (skin test and specific serum IgE), allergic rhinitis, peripheral blood eosinophil counts, asthma, and atopic dermatitis during the first 6 years of life.<br><br>RESULTS: We found that bacterial diversity in the early intestinal flora 1 and 12 months after birth was inversely associated with the risk of allergic sensitization (serum specific IgE P = .003; skin prick test P = .017), peripheral blood eosinophils (P = .034), and allergic rhinitis (P = .007). There was no association with the development of asthma or atopic dermatitis.<br><br>CONCLUSIONS: Reduced bacterial diversity of the infant's intestinal flora was associated with increased risk of allergic sensitization, allergic rhinitis, and peripheral blood eosinophilia, but not asthma or atopic dermatitis, in the first 6 years of life. These results support the general hypothesis that an imbalance in the intestinal microbiome is influencing the development of lifestyle-related disorders, such as allergic disease.}, }
@article {pmid21775143, year = {2011}, author = {Frank, DN and Zhu, W and Sartor, RB and Li, E}, title = {Investigating the biological and clinical significance of human dysbioses.}, journal = {Trends in microbiology}, volume = {19}, number = {9}, pages = {427-434}, pmid = {21775143}, issn = {1878-4380}, support = {R21 HG005964-01/HG/NHGRI NIH HHS/United States ; DK53347/DK/NIDDK NIH HHS/United States ; HG005964/HG/NHGRI NIH HHS/United States ; UH2 DK083994-01/DK/NIDDK NIH HHS/United States ; P30 DK034987/DK/NIDDK NIH HHS/United States ; R01 HD059527/HD/NICHD NIH HHS/United States ; R01 DK053347/DK/NIDDK NIH HHS/United States ; P40 RR018603-01A1/RR/NCRR NIH HHS/United States ; R21 HG005964/HG/NHGRI NIH HHS/United States ; UH2 DK083994/DK/NIDDK NIH HHS/United States ; RR018603/RR/NCRR NIH HHS/United States ; DK034987/DK/NIDDK NIH HHS/United States ; R01 DK053347-02/DK/NIDDK NIH HHS/United States ; P40 RR018603/RR/NCRR NIH HHS/United States ; HD059527/HD/NICHD NIH HHS/United States ; }, mesh = {Animals ; Genetics, Medical ; *Host-Pathogen Interactions ; Humans ; Immunity ; *Metagenome ; }, abstract = {Culture-independent microbiological technologies that interrogate complex microbial populations without prior axenic culture, coupled with high-throughput DNA sequencing, have revolutionized the scale, speed and economics of microbial ecological studies. Their application to the medical realm has led to a highly productive merger of clinical, experimental and environmental microbiology. The functional roles played by members of the human microbiota are being actively explored through experimental manipulation of animal model systems and studies of human populations. In concert, these studies have appreciably expanded our understanding of the composition and dynamics of human-associated microbial communities (microbiota). Of note, several human diseases have been linked to alterations in the composition of resident microbial communities, so-called dysbiosis. However, how changes in microbial communities contribute to disease etiology remains poorly defined. Correlation of microbial composition represents integration of only two datasets (phenotype and microbial composition). This article explores strategies for merging the human microbiome data with multiple additional datasets (e.g. host single nucleotide polymorphisms and host gene expression) and for integrating patient-based data with results from experimental animal models to gain deeper understanding of how host-microbe interactions impact disease.}, }
@article {pmid21772835, year = {2011}, author = {Young, VB and Kahn, SA and Schmidt, TM and Chang, EB}, title = {Studying the Enteric Microbiome in Inflammatory Bowel Diseases: Getting through the Growing Pains and Moving Forward.}, journal = {Frontiers in microbiology}, volume = {2}, number = {}, pages = {144}, pmid = {21772835}, issn = {1664-302X}, support = {UH3 DK083993/DK/NIDDK NIH HHS/United States ; }, abstract = {In this commentary, we will review some of the early efforts aimed at understanding the role of the enteric microbiota in the causality of inflammatory bowel diseases. By examining these studies and drawing on our own experiences bridging clinical gastroenterology and microbial ecology as part of the NIH-funded Human Microbiome Project (Turnbaugh et al., 2007), we hope to help define some of the "growing pains" that have hampered these initial efforts. It is our sincere hope that this discussion will help advance future efforts in this area by identifying current challenges and limitations and by suggesting strategies to overcome these obstacles.}, }
@article {pmid21755095, year = {2011}, author = {Liu, P and Meagher, RJ and Light, YK and Yilmaz, S and Chakraborty, R and Arkin, AP and Hazen, TC and Singh, AK}, title = {Microfluidic fluorescence in situ hybridization and flow cytometry (μFlowFISH).}, journal = {Lab on a chip}, volume = {11}, number = {16}, pages = {2673-2679}, pmid = {21755095}, issn = {1473-0189}, support = {R01 DE020891/DE/NIDCR NIH HHS/United States ; R01 DE020891-03/DE/NIDCR NIH HHS/United States ; 5 R01 DE020891/DE/NIDCR NIH HHS/United States ; }, mesh = {Bacteria/*chemistry ; Flow Cytometry/*methods ; In Situ Hybridization, Fluorescence/*methods ; Microfluidic Analytical Techniques/*methods ; RNA, Ribosomal, 16S/*analysis ; *Water Microbiology ; }, abstract = {We describe an integrated microfluidic device (μFlowFISH) capable of performing 16S rRNA fluorescence in situ hybridization (FISH) followed by flow cytometric detection for identifying bacteria in natural microbial communities. The device was used for detection of species involved in bioremediation of Cr(vi) and other metals in groundwater samples from a highly-contaminated environmental site (Hanford, WA, USA). The μFlowFISH seamlessly integrates two components: a hybridization chamber formed between two photopolymerized membranes, where cells and probes are electrophoretically loaded, incubated and washed, and a downstream cross structure for electrokinetically focusing cells into a single-file flow for flow cytometry analysis. The device is capable of analyzing a wide variety of bacteria including aerobic, facultative and anaerobic bacteria and was initially tested and validated using cultured microbes, including Escherichia coli, as well as two strains isolated from Hanford site: Desulfovibrio vulgaris strain RCH1, and Pseudomonas sp.strain RCH2 that are involved in Cr(vi) reduction and immobilization. Combined labeling and detection efficiencies of 74-97% were observed in experiments with simple mixtures of cultured cells, confirming specific labeling. Results obtained were in excellent agreement with those obtained by conventional flow cytometry confirming the accuracy of μFlowFISH. Finally, the device was used for analyzing water samples collected on different dates from the Hanford site. We were able to monitor the numbers of Pseudomonas sp. with only 100-200 cells loaded into the microchip. The μFlowFISH approach provides an automated platform for quantitative detection of microbial cells from complex samples, and is ideally suited for analysis of precious samples with low cell numbers such as those found at extreme environmental niches, bioremediation sites, and the human microbiome.}, }
@article {pmid21729521, year = {2011}, author = {Wu, KF and Zheng, GG and Ma, XT and Song, YH and Zhu, XF}, title = {[Mechanism of leukemia relapse: novel insights on old problem].}, journal = {Zhongguo shi yan xue ye xue za zhi}, volume = {19}, number = {3}, pages = {557-560}, pmid = {21729521}, issn = {1009-2137}, mesh = {Cell Fusion ; Humans ; Leukemia/*pathology ; Neoplasm, Residual/pathology ; Recurrence ; }, abstract = {Relapse, which puzzled several generations of hematologists, is the bottle-neck of radical treatment for leukemias. The progress of Human Microbiome Project at the beginning of 21st century suggested that human body was a super-organism constituted by the core of human cells and symbiotic microorganisms. The elucidation and characterization of endogenous retrovirus and prion protein suggested the possible effects of co-evolutional microorganisms on human health. Recently, the elucidation of the roles of tunneling nanotubes in intercellular communication and transportation suggested a novel way for cellular communication and transport of oncogenic materials. The role and significance of in vivo cell fusion have been studied in more detail. On the other hand, donor cell leukemia was reported. All of these approaches provide novel insights for studying the mechanism of leukemia relapse. Based on previous work, the authors suggest the hypothesis: there are two possible mechanisms for the relapse of leukemias: the minimal residual disease (MRD) and intercellular transportation of oncogenic materials.}, }
@article {pmid21720391, year = {2011}, author = {Gonzalez, A and Clemente, JC and Shade, A and Metcalf, JL and Song, S and Prithiviraj, B and Palmer, BE and Knight, R}, title = {Our microbial selves: what ecology can teach us.}, journal = {EMBO reports}, volume = {12}, number = {8}, pages = {775-784}, pmid = {21720391}, issn = {1469-3178}, support = {//Howard Hughes Medical Institute/United States ; }, mesh = {Animals ; *Ecology ; *Ecosystem ; Humans ; *Metagenome ; Precision Medicine ; Research ; }, abstract = {Advances in DNA sequencing have allowed us to characterize microbial communities--including those associated with the human body--at a broader range of spatial and temporal scales than ever before. We can now answer fundamental questions that were previously inaccessible and use well-tested ecological theories to gain insight into changes in the microbiome that are associated with normal development and human disease. Perhaps unsurprisingly, the ecosystems associated with our body follow trends identified in communities at other sites and scales, and thus studies of the microbiome benefit from ecological insight. Here, we assess human microbiome research in the context of ecological principles and models, focusing on diversity, biological drivers of community structure, spatial patterning and temporal dynamics, and suggest key directions for future research that will bring us closer to the goal of building predictive models for personalized medicine.}, }
@article {pmid21690380, year = {2011}, author = {Mitri, S and Xavier, JB and Foster, KR}, title = {Social evolution in multispecies biofilms.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {108 Suppl 2}, number = {Suppl 2}, pages = {10839-10846}, pmid = {21690380}, issn = {1091-6490}, support = {242670/ERC_/European Research Council/International ; }, mesh = {Bacteria/growth &amp; development ; Biofilms/*growth &amp; development ; *Biological Evolution ; Computer Simulation ; Ecology ; *Environment ; Genome, Bacterial ; Species Specificity ; }, abstract = {Microbial ecology is revealing the vast diversity of strains and species that coexist in many environments, ranging from free-living communities to the symbionts that compose the human microbiome. In parallel, there is growing evidence of the importance of cooperative phenotypes for the growth and behavior of microbial groups. Here we ask: How does the presence of multiple species affect the evolution of cooperative secretions? We use a computer simulation of spatially structured cellular groups that captures key features of their biology and physical environment. When nutrient competition is strong, we find that the addition of new species can inhibit cooperation by eradicating secreting strains before they can become established. When nutrients are abundant and many species mix in one environment, however, our model predicts that secretor strains of any one species will be surrounded by other species. This "social insulation" protects secretors from competition with nonsecretors of the same species and can improve the prospects of within-species cooperation. We also observe constraints on the evolution of mutualistic interactions among species, because it is difficult to find conditions that simultaneously favor both within- and among-species cooperation. Although relatively simple, our model reveals the richness of interactions between the ecology and social evolution of multispecies microbial groups, which can be critical for the evolution of cooperation.}, }
@article {pmid21678649, year = {2011}, author = {Solt, I and Kim, MJ and Offer, C}, title = {[The human microbiome].}, journal = {Harefuah}, volume = {150}, number = {5}, pages = {484-488}, pmid = {21678649}, issn = {0017-7768}, mesh = {Female ; Gastrointestinal Tract/microbiology ; Humans ; *Metagenome ; Metagenomics/*methods ; Mouth/microbiology ; Nasopharynx/microbiology ; Skin/microbiology ; Urogenital System/microbiology ; }, abstract = {The complex microbial populations that colonize the human body form the human microbiome. The human microbiota may contain 1014) cells, an order of magnitude greater than the number of the human cells, and can express 100 times more genes than the human genome. The metagenome is the collective genomes of the human and its microbial flora. Major international colLaborative efforts currently explore the diverse human microbiomes from five different body areas: the nasopharyngeal, gastrointestinal and female urogenital tracts, the oral cavity and the skin. Defining the complexity of the human microbiome in health and disease will enhance the understanding of multiple pathological mechanisms and facilitate the development of novel diagnostic tools and therapeutic interventions.}, }
@article {pmid21635714, year = {2011}, author = {Weinstock, GM}, title = {The volatile microbiome.}, journal = {Genome biology}, volume = {12}, number = {5}, pages = {114}, pmid = {21635714}, issn = {1474-760X}, abstract = {The first detailed temporal study of the human microbiome shows that individual body habitats exhibit surprising variation over time yet maintain distinguishable community structures.}, }
@article {pmid21624126, year = {2011}, author = {Caporaso, JG and Lauber, CL and Costello, EK and Berg-Lyons, D and Gonzalez, A and Stombaugh, J and Knights, D and Gajer, P and Ravel, J and Fierer, N and Gordon, JI and Knight, R}, title = {Moving pictures of the human microbiome.}, journal = {Genome biology}, volume = {12}, number = {5}, pages = {R50}, pmid = {21624126}, issn = {1474-760X}, support = {AI083264/AI/NIAID NIH HHS/United States ; HG004872-02S1/HG/NHGRI NIH HHS/United States ; AI070921/AI/NIAID NIH HHS/United States ; DK078669/DK/NIDDK NIH HHS/United States ; //Howard Hughes Medical Institute/United States ; HG004872/HG/NHGRI NIH HHS/United States ; }, mesh = {Bacteria/classification/*genetics ; Computer Simulation ; Gastrointestinal Tract/*microbiology ; Genomics/*methods ; High-Throughput Nucleotide Sequencing ; Humans ; Inflammatory Bowel Diseases/microbiology ; Metagenome/*genetics ; Obesity/microbiology ; Organ Specificity ; RNA, Ribosomal, 16S/genetics ; Seasons ; Time Factors ; }, abstract = {BACKGROUND: Understanding the normal temporal variation in the human microbiome is critical to developing treatments for putative microbiome-related afflictions such as obesity, Crohn’s disease, inflammatory bowel disease and malnutrition. Sequencing and computational technologies, however, have been a limiting factor in performing dense time series analysis of the human microbiome. Here, we present the largest human microbiota time series analysis to date, covering two individuals at four body sites over 396 timepoints.<br><br>RESULTS: We find that despite stable differences between body sites and individuals, there is pronounced variability in an individual&#x2019;s microbiota across months, weeks and even days. Additionally, only a small fraction of the total taxa found within a single body site appear to be present across all time points, suggesting that no core temporal microbiome exists at high abundance (although some microbes may be present but drop below the detection threshold). Many more taxa appear to be persistent but non-permanent community members.<br><br>CONCLUSIONS: DNA sequencing and computational advances described here provide the ability to go beyond infrequent snapshots of our human-associated microbial ecology to high-resolution assessments of temporal variations over protracted periods, within and between body habitats and individuals. This capacity will allow us to define normal variation and pathologic states, and assess responses to therapeutic interventions.}, }
@article {pmid21585298, year = {2011}, author = {van der Greef, J}, title = {The 27th Montreux Symposium on LC-MS.}, journal = {Bioanalysis}, volume = {3}, number = {10}, pages = {1057-1059}, doi = {10.4155/bio.11.108}, pmid = {21585298}, issn = {1757-6199}, mesh = {Biotechnology ; Chromatography, Liquid/*methods ; Humans ; Mass Spectrometry/*methods ; Metabolomics ; Metagenome ; Miniaturization ; Pharmaceutical Preparations/analysis ; Precision Medicine ; }, abstract = {The recent Montreux Symposium on LC-MS held in 2010 provided an insight into the key areas of present achievements and future developments in LC-MS. This domain is rapidly changing from a technology- to an application-driven enterprise. New demands for advanced options are coming from (medical) biology, biotechnology, pharmaceutical and nutrition research. In particular, new diagnostic options based on -omics technologies, miniaturization and advanced data handling are rapidly being developed in relation to questions coming from personalized medicine, claim support in nutritional research, biotechnology production support and the human microbiome.}, }
@article {pmid21559529, year = {2011}, author = {Saulnier, DM and Santos, F and Roos, S and Mistretta, TA and Spinler, JK and Molenaar, D and Teusink, B and Versalovic, J}, title = {Exploring metabolic pathway reconstruction and genome-wide expression profiling in Lactobacillus reuteri to define functional probiotic features.}, journal = {PloS one}, volume = {6}, number = {4}, pages = {e18783}, pmid = {21559529}, issn = {1932-6203}, support = {P30 DK56338/DK/NIDDK NIH HHS/United States ; R01 DK065075/DK/NIDDK NIH HHS/United States ; P30 DK056338/DK/NIDDK NIH HHS/United States ; R21 AT003482/AT/NCCIH NIH HHS/United States ; R01 AT004326/AT/NCCIH NIH HHS/United States ; }, mesh = {Bacterial Adhesion ; Biofilms ; Gene Expression Profiling ; *Gene Expression Regulation, Bacterial ; *Genome, Bacterial ; Humans ; Limosilactobacillus reuteri/*genetics ; Metabolic Networks and Pathways/genetics ; Milk, Human/microbiology ; Multigene Family ; Polysaccharides/chemistry ; Probiotics/*metabolism ; Species Specificity ; Transcriptome ; }, abstract = {The genomes of four Lactobacillus reuteri strains isolated from human breast milk and the gastrointestinal tract have been recently sequenced as part of the Human Microbiome Project. Preliminary genome comparisons suggested that these strains belong to two different clades, previously shown to differ with respect to antimicrobial production, biofilm formation, and immunomodulation. To explain possible mechanisms of survival in the host and probiosis, we completed a detailed genomic comparison of two breast milk-derived isolates representative of each group: an established probiotic strain (L. reuteri ATCC 55730) and a strain with promising probiotic features (L. reuteri ATCC PTA 6475). Transcriptomes of L. reuteri strains in different growth phases were monitored using strain-specific microarrays, and compared using a pan-metabolic model representing all known metabolic reactions present in these strains. Both strains contained candidate genes involved in the survival and persistence in the gut such as mucus-binding proteins and enzymes scavenging reactive oxygen species. A large operon predicted to encode the synthesis of an exopolysaccharide was identified in strain 55730. Both strains were predicted to produce health-promoting factors, including antimicrobial agents and vitamins (folate, vitamin B(12)). Additionally, a complete pathway for thiamine biosynthesis was predicted in strain 55730 for the first time in this species. Candidate genes responsible for immunomodulatory properties of each strain were identified by transcriptomic comparisons. The production of bioactive metabolites by human-derived probiotics may be predicted using metabolic modeling and transcriptomics. Such strategies may facilitate selection and optimization of probiotics for health promotion, disease prevention and amelioration.}, }
@article {pmid21544197, year = {2011}, author = {Griffen, AL and Beall, CJ and Firestone, ND and Gross, EL and Difranco, JM and Hardman, JH and Vriesendorp, B and Faust, RA and Janies, DA and Leys, EJ}, title = {CORE: a phylogenetically-curated 16S rDNA database of the core oral microbiome.}, journal = {PloS one}, volume = {6}, number = {4}, pages = {e19051}, pmid = {21544197}, issn = {1932-6203}, support = {R01 DE010467/DE/NIDCR NIH HHS/United States ; R01 DE016125/DE/NIDCR NIH HHS/United States ; R01DE016125/DE/NIDCR NIH HHS/United States ; R01DE010467/DE/NIDCR NIH HHS/United States ; }, mesh = {DNA, Ribosomal/*genetics ; Humans ; Metagenome/*genetics ; Mouth/*microbiology ; Phylogeny ; }, abstract = {Comparing bacterial 16S rDNA sequences to GenBank and other large public databases via BLAST often provides results of little use for identification and taxonomic assignment of the organisms of interest. The human microbiome, and in particular the oral microbiome, includes many taxa, and accurate identification of sequence data is essential for studies of these communities. For this purpose, a phylogenetically curated 16S rDNA database of the core oral microbiome, CORE, was developed. The goal was to include a comprehensive and minimally redundant representation of the bacteria that regularly reside in the human oral cavity with computationally robust classification at the level of species and genus. Clades of cultivated and uncultivated taxa were formed based on sequence analyses using multiple criteria, including maximum-likelihood-based topology and bootstrap support, genetic distance, and previous naming. A number of classification inconsistencies for previously named species, especially at the level of genus, were resolved. The performance of the CORE database for identifying clinical sequences was compared to that of three publicly available databases, GenBank nr/nt, RDP and HOMD, using a set of sequencing reads that had not been used in creation of the database. CORE offered improved performance compared to other public databases for identification of human oral bacterial 16S sequences by a number of criteria. In addition, the CORE database and phylogenetic tree provide a framework for measures of community divergence, and the focused size of the database offers advantages of efficiency for BLAST searching of large datasets. The CORE database is available as a searchable interface and for download at http://microbiome.osu.edu.}, }
@article {pmid21540692, year = {2011}, author = {Gregory, KE}, title = {Microbiome aspects of perinatal and neonatal health.}, journal = {The Journal of perinatal &amp; neonatal nursing}, volume = {25}, number = {2}, pages = {158-62; quiz 163-4}, pmid = {21540692}, issn = {1550-5073}, support = {K23 NR011320/NR/NINR NIH HHS/United States ; }, mesh = {DNA, Bacterial ; Female ; Genes, Bacterial ; Gram-Negative Bacteria/genetics ; Gram-Positive Bacteria/genetics ; Humans ; *Infant Welfare ; Infant, Newborn ; Infant, Newborn, Diseases/*microbiology ; Male ; *Maternal Welfare ; Metagenome/*physiology ; Nursing Research ; Perinatal Care ; Pregnancy ; Sensitivity and Specificity ; }, abstract = {Our human cells are outnumbered 10 to 1 by bacterial cells. For this reason, the role of microorganisms, specifically bacteria, in health and disease has brought forth intense research via the Human Microbiome Project. The Human Microbiome Project is a National Institutes of Health sponsored effort to build upon the Human Genome Project in understanding human genetic and physiologic diversity. Perinatal and neonatal health represents areas of high importance for knowledge generated by the Human Microbiome Project as the microbiome is largely influenced during pregnancy, birth, and the neonatal period by nutrition, lifestyle, environmental factors of care, and the administration of medications, specifically antibiotics. As nurses have a depth of expertise in these areas, they will make a significant contribution toward better understanding the role of the microbiome in disease, and how to manipulate the microbiome to advantage patients toward health. This article describes the human microbiome and why it is important to overall health and disease. Three major unsolved problems in perinatal and neonatal health including (1) preterm birth; (2) the neonatal consequences of vaginal versus cesarean birth; and (3) neonatal gastrointestinal disease, specifically, necrotizing enterocolitis, are discussed in the context of current and future research on the human microbiome.}, }
@article {pmid21524302, year = {2011}, author = {DeSantis, TZ and Keller, K and Karaoz, U and Alekseyenko, AV and Singh, NN and Brodie, EL and Pei, Z and Andersen, GL and Larsen, N}, title = {Simrank: Rapid and sensitive general-purpose k-mer search tool.}, journal = {BMC ecology}, volume = {11}, number = {}, pages = {11}, pmid = {21524302}, issn = {1472-6785}, support = {AI075410-01/AI/NIAID NIH HHS/United States ; U01-HG004866/HG/NHGRI NIH HHS/United States ; UH2/UH3CA140233/CA/NCI NIH HHS/United States ; }, mesh = {Computational Biology ; DNA ; *Databases, Bibliographic ; *Databases, Factual ; *Molecular Biology ; Proteins ; RNA ; *Software ; }, abstract = {BACKGROUND: Terabyte-scale collections of string-encoded data are expected from consortia efforts such as the Human Microbiome Project http://nihroadmap.nih.gov/hmp. Intra- and inter-project data similarity searches are enabled by rapid k-mer matching strategies. Software applications for sequence database partitioning, guide tree estimation, molecular classification and alignment acceleration have benefited from embedded k-mer searches as sub-routines. However, a rapid, general-purpose, open-source, flexible, stand-alone k-mer tool has not been available.<br><br>RESULTS: Here we present a stand-alone utility, Simrank, which allows users to rapidly identify database strings the most similar to query strings. Performance testing of Simrank and related tools against DNA, RNA, protein and human-languages found Simrank 10X to 928X faster depending on the dataset.<br><br>CONCLUSIONS: Simrank provides molecular ecologists with a high-throughput, open source choice for comparing large sequence sets to find similarity.}, }
@article {pmid21490274, year = {2011}, author = {Sonnenburg, JL and Fischbach, MA}, title = {Community health care: therapeutic opportunities in the human microbiome.}, journal = {Science translational medicine}, volume = {3}, number = {78}, pages = {78ps12}, pmid = {21490274}, issn = {1946-6242}, support = {R01 DK085025/DK/NIDDK NIH HHS/United States ; R01 DK085025-03/DK/NIDDK NIH HHS/United States ; DP2 OD007290/OD/NIH HHS/United States ; DP2 OD006515/OD/NIH HHS/United States ; }, mesh = {Community Health Services/*methods ; Humans ; *Metagenome ; }, abstract = {We are never alone. Humans coexist with diverse microbial species that live within and upon us--our so-called microbiota. It is now clear that this microbial community is essentially another organ that plays a fundamental role in human physiology and disease. Basic and translational research efforts have begun to focus on deciphering mechanisms of microbiome function--and learning how to manipulate it to benefit human health. In this Perspective, we discuss therapeutic opportunities in the human microbiome.}, }
@article {pmid21485746, year = {2011}, author = {Gonzalez, A and Stombaugh, J and Lozupone, C and Turnbaugh, PJ and Gordon, JI and Knight, R}, title = {The mind-body-microbial continuum.}, journal = {Dialogues in clinical neuroscience}, volume = {13}, number = {1}, pages = {55-62}, pmid = {21485746}, issn = {1294-8322}, support = {P01 DK078669/DK/NIDDK NIH HHS/United States ; P50 GM068763/GM/NIGMS NIH HHS/United States ; R01 HG004872/HG/NHGRI NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {*Behavioral Symptoms/genetics/microbiology/therapy ; Gastrointestinal Tract/microbiology ; Genome, Bacterial/genetics ; Humans ; *Mental Disorders/genetics/microbiology/therapy ; *Metagenome ; Metagenomics/methods ; Neurotransmitter Agents/therapeutic use ; }, abstract = {Our understanding of the vast collection of microbes that live on and inside us (microbiota) and their collective genes (microbiome) has been revolutionized by culture-independent "metagenomic" techniques and DNA sequencing technologies. Most of our microbes live in our gut, where they function as a metabolic organ and provide attributes not encoded in our human genome. Metagenomic studies are revealing shared and distinctive features of microbial communities inhabiting different humans. A central question in psychiatry is the relative role of genes and environment in shaping behavior. The human microbiome serves as the interface between our genes and our history of environmental exposures; explorations of our microbiomes thus offer the possibility of providing new insights into our neurodevelopment and our behavioral phenotypes by affecting complex processes such as inter- and intra personal variations in cognition, personality, mood, sleep, and eating behavior, and perhaps even a variety of neuropsychiatric diseases ranging from affective disorders to autism. Better understanding of microbiome-encoded pathways for xenobiotic metabolism also has important implications for improving the efficacy of pharmacologic interventions with neuromodulatory agents.}, }
@article {pmid21448201, year = {2011}, author = {Murgas Torrazza, R and Neu, J}, title = {The developing intestinal microbiome and its relationship to health and disease in the neonate.}, journal = {Journal of perinatology : official journal of the California Perinatal Association}, volume = {31 Suppl 1}, number = {}, pages = {S29-34}, doi = {10.1038/jp.2010.172}, pmid = {21448201}, issn = {1476-5543}, mesh = {Animals ; Anti-Bacterial Agents/pharmacology ; Cesarean Section ; Delivery, Obstetric ; Fetus/microbiology ; Humans ; *Infant, Newborn ; Intestines/*microbiology ; *Metagenome ; Prebiotics ; Probiotics/pharmacology ; }, abstract = {The intestinal microbiota normally exists in a commensal and/or symbiotic relationship with the host. In the past few years, emerging technologies derived largely from the Human Genome Project have been applied to evaluating the intestinal microbiota and new discoveries using these techniques have prompted new initiatives such as the Human Microbiome Roadmap designed to evaluate the role of the intestinal microbiome in health and disease. In this review, we wish to focus on some new developments in this area and discuss some of the effects of medical manipulations such as antibiotics, probiotics, prebiotics and C-section versus vaginal delivery on the intestinal microbiota.}, }
@article {pmid21422915, year = {2011}, author = {Morowitz, MJ and Babrowski, T and Carlisle, EM and Olivas, A and Romanowski, KS and Seal, JB and Liu, DC and Alverdy, JC}, title = {The human microbiome and surgical disease.}, journal = {Annals of surgery}, volume = {253}, number = {6}, pages = {1094-1101}, pmid = {21422915}, issn = {1528-1140}, support = {R01 GM062344/GM/NIGMS NIH HHS/United States ; R01 GM62344-09/GM/NIGMS/GM/NIGMS NIH HHS/United States ; }, mesh = {General Surgery ; Genetic Techniques ; Humans ; Metagenome/*genetics/physiology ; Microbiological Techniques ; Symbiosis/physiology ; }, abstract = {OBJECTIVE: The purpose of this review article is to summarize what is currently known about microbes associated with the human body and to provide examples of how this knowledge impacts the care of surgical patients.<br><br>BACKGROUND: Pioneering research over the past decade has demonstrated that human beings live in close, constant contact with dynamic communities of microbial organisms. This new reality has wide-ranging implications for the care of surgical patients.<br><br>METHODS AND RESULTS: Recent advances in the culture-independent study of the human microbiome are reviewed. To illustrate the translational relevance of these studies to surgical disease, we discuss in detail what is known about the role of microbes in the pathogenesis of obesity, gastrointestinal malignancies, Crohn disease, and perioperative complications including surgical site infections and sepsis. The topics of mechanical bowel preparation and perioperative antibiotics are also discussed.<br><br>CONCLUSIONS: Heightened understanding of the microbiome in coming years will likely offer opportunities to refine the prevention and treatment of a wide variety of surgical conditions.}, }
@article {pmid21420503, year = {2011}, author = {Dridi, B and Raoult, D and Drancourt, M}, title = {Archaea as emerging organisms in complex human microbiomes.}, journal = {Anaerobe}, volume = {17}, number = {2}, pages = {56-63}, doi = {10.1016/j.anaerobe.2011.03.001}, pmid = {21420503}, issn = {1095-8274}, mesh = {Anaerobiosis ; *Biodiversity ; Female ; Humans ; Intestinal Mucosa/microbiology ; *Metagenome ; Methanobacteriaceae/classification/*isolation &amp; purification/metabolism ; Methanobrevibacter/classification/*isolation &amp; purification/metabolism ; Mouth Mucosa/microbiology ; Vagina/microbiology ; }, abstract = {In this work, we review the state of knowledge of Archaea associated with the human microbiome. These prokaryotes, initially discovered in extreme environments, were named Archaea because these environments were thought to be the most primitive on Earth. Further research revealed that this terminology is misleading because these organisms were later found in various non-extreme environments, including the human host. Further examination of the human microbiome has enabled the isolation of three archaeal species, Methanobrevibacter smithii, Methanosphaera stadtmanae and Methanobrevibacter oralis, which are associated with oral, intestinal and vaginal mucosae in humans. Moreover, molecular studies including metagenomic analyses detected DNA sequences indicative of the presence of additional methanogenic and non-methanogenic Archaea in the human intestinal tract. All three culturable Archaea are strict anaerobes, although their potential role in human diseases remains to be established. Future research aims to detect and culture additional human mucosa-associated Archaea and to look for their presence in additional human tissues, to establish their role in human infections involving complex flora.}, }
@article {pmid21376215, year = {2011}, author = {Carlisle, EM and Morowitz, MJ}, title = {Pediatric surgery and the human microbiome.}, journal = {Journal of pediatric surgery}, volume = {46}, number = {3}, pages = {577-584}, doi = {10.1016/j.jpedsurg.2010.12.018}, pmid = {21376215}, issn = {1531-5037}, mesh = {Adolescent ; Animals ; Bacterial Translocation ; Bariatric Surgery ; Child ; Child, Preschool ; Cross Infection/complications/microbiology ; Diet ; Disease Susceptibility ; Enterocolitis, Necrotizing/*microbiology/surgery ; *General Surgery ; Germ-Free Life ; Humans ; Infant ; Infant, Newborn ; Inflammatory Bowel Diseases/*microbiology/surgery ; Intensive Care Units, Neonatal ; Intestines/*microbiology ; *Metagenome ; Mice ; Microbial Consortia/*physiology ; Obesity/*microbiology/surgery ; *Pediatrics ; Postoperative Complications/etiology/microbiology/prevention &amp; control ; Pouchitis/etiology/microbiology/prevention &amp; control ; Probiotics/therapeutic use ; Species Specificity ; Virulence ; }, abstract = {Bold advances in the past decade have made it possible to carefully study the contributions of microbes to normal human development and to disease pathogenesis. The intestinal microbiota has been implicated in adult diseases ranging from obesity to cancer, but there have been relatively few investigations of bacteria in surgical diseases of infancy and childhood. In this review, we discuss how novel culture-independent approaches have been harnessed to profile microbes present within clinical specimens. Unique features of the pediatric microbiota and innovative approaches to manipulate the gut flora are also reviewed. Finally, we detail the contributions of gut microbes to 3 diseases relevant to pediatric surgeons: necrotizing enterocolitis, obesity, and inflammatory bowel disease. Current and future research regarding the pediatric microbiota is likely to translate to improved outcomes for infants and children with surgical diseases.}, }
@article {pmid21361774, year = {2011}, author = {Ram, JL and Karim, AS and Sendler, ED and Kato, I}, title = {Strategy for microbiome analysis using 16S rRNA gene sequence analysis on the Illumina sequencing platform.}, journal = {Systems biology in reproductive medicine}, volume = {57}, number = {3}, pages = {162-170}, doi = {10.3109/19396368.2011.555598}, pmid = {21361774}, issn = {1939-6376}, mesh = {DNA Primers/chemistry ; DNA, Bacterial/genetics ; Desulfovibrio desulfuricans/genetics ; Escherichia coli/genetics ; Humans ; Metagenome/*genetics ; Pilot Projects ; Polymerase Chain Reaction/*methods ; RNA, Ribosomal, 16S/*genetics ; Sequence Analysis, DNA/*methods ; Streptococcus pyogenes/genetics ; Urogenital System/*microbiology ; }, abstract = {Understanding the identity and changes of organisms in the urogenital and other microbiomes of the human body may be key to discovering causes and new treatments of many ailments, such as vaginosis. High-throughput sequencing technologies have recently enabled discovery of the great diversity of the human microbiome. The cost per base of many of these sequencing platforms remains high (thousands of dollars per sample); however, the Illumina Genome Analyzer (IGA) is estimated to have a cost per base less than one-fifth of its nearest competitor. The main disadvantage of the IGA for sequencing PCR-amplified 16S rRNA genes is that the maximum read-length of the IGA is only 100 bases; whereas, at least 300 bases are needed to obtain phylogenetically informative data down to the genus and species level. In this paper we describe and conduct a pilot test of a multiplex sequencing strategy suitable for achieving total reads of > 300 bases per extracted DNA molecule on the IGA. Results show that all proposed primers produce products of the expected size and that correct sequences can be obtained, with all proposed forward primers. Various bioinformatic optimization of the Illumina Bustard analysis pipeline proved necessary to extract the correct sequence from IGA image data, and these modifications of the data files indicate that further optimization of the analysis pipeline may improve the quality rankings of the data and enable more sequence to be correctly analyzed. The successful application of this method could result in an unprecedentedly deep description (800,000 taxonomic identifications per sample) of the urogenital and other microbiomes in a large number of samples at a reasonable cost per sample.}, }
@article {pmid21354482, year = {2011}, author = {Liu, PF and Nakatsuji, T and Zhu, W and Gallo, RL and Huang, CM}, title = {Passive immunoprotection targeting a secreted CAMP factor of Propionibacterium acnes as a novel immunotherapeutic for acne vulgaris.}, journal = {Vaccine}, volume = {29}, number = {17}, pages = {3230-3238}, pmid = {21354482}, issn = {1873-2518}, support = {R21-I58002-01//PHS HHS/United States ; 1R41AR056169/AR/NIAMS NIH HHS/United States ; R01-AI067395-01/AI/NIAID NIH HHS/United States ; R01 AI083358/AI/NIAID NIH HHS/United States ; R41 AR056169/AR/NIAMS NIH HHS/United States ; R21-R022754-01//PHS HHS/United States ; R01 AI067395/AI/NIAID NIH HHS/United States ; }, mesh = {Acne Vulgaris/*therapy ; Animals ; Antibodies, Bacterial/*administration &amp; dosage ; Antibodies, Neutralizing/administration &amp; dosage ; Bacterial Load ; Bacterial Proteins/*antagonists &amp; inhibitors/immunology ; Female ; Immunization, Passive/*methods ; Immunotherapy/*methods ; Mice ; Mice, Inbred ICR ; Propionibacterium acnes/*immunology/pathogenicity ; Virulence Factors/*administration &amp; dosage/immunology ; }, abstract = {Propionibacterium acnes (P. acnes) bacteria play a key role in the pathogenesis of acne vulgaris. Although our previous studies have demonstrated that vaccines targeting a surface sialidase or bacterial particles exhibit a preventive effect against P. acnes, the lack of therapeutic activities and incapability of neutralizing secretory virulence factors motivate us to generate novel immunotherapeutics. In this study, we develop an immunotherapeutic antibody to secretory Christie-Atkins-Munch-Peterson (CAMP) factor of P. acnes. Via agroinfiltration, P. acnes CAMP factor was encapsulated into the leaves of radishes. ICR mice intranasally immunized with whole leaves expressing CAMP factor successfully produced neutralizing antibodies that efficiently attenuated P. acnes-induced ear swelling and production of macrophage-inflammatory protein-2. Passive neutralization of CAMP factor enhanced immunity to eradicate P. acnes at the infection site without influencing bacterial growth elsewhere. We propose that CAMP factor is a novel therapeutic target for the treatment of various P. acnes-associated diseases and highlight the concept of neutralizing P. acnes virulence without disturbing the bacterial commensalism in human microbiome.}, }
@article {pmid21266343, year = {2010}, author = {Liu, Y and Zhang, C and Zhao, L and Nardini, C}, title = {Adapting functional genomic tools to metagenomic analyses: investigating the role of gut bacteria in relation to obesity.}, journal = {Briefings in functional genomics}, volume = {9}, number = {5-6}, pages = {355-361}, pmid = {21266343}, issn = {2041-2657}, mesh = {Animals ; *Bacteria/classification/genetics ; Diet ; Gastrointestinal Tract/*microbiology ; Genes, rRNA ; Genome/genetics ; Genomics/*methods ; Humans ; Metagenome/genetics ; Metagenomics/*methods ; Mice ; Mice, Knockout ; Obesity/genetics/*microbiology ; Oligonucleotide Array Sequence Analysis/methods ; Software ; }, abstract = {With the expanding availability of sequencing technologies, research previously centered on the human genome can now afford to include the study of humans' internal ecosystem (human microbiome). Given the scale of the data involved in this metagenomic research (two orders of magnitude larger than the human genome) and their importance in relation to human health, it is crucial to guarantee (along with the appropriate data collection and taxonomy) proper tools for data analysis. We propose to adapt the approaches defined for the analysis of gene-expression microarray in order to infer information in metagenomics. In particular, we applied SAM, a broadly used tool for the identification of differentially expressed genes among different samples classes, to a reported dataset on a research model with mice of two genotypes (a high density lipoprotein knockout mouse and its wild-type counterpart). The data contain two different diets (high-fat or normal-chow) to ensure the onset of obesity, prodrome of metabolic syndromes (MS). By using 16S rRNA gene as a genomic diversity marker, we illustrate how this approach can identify bacterial populations differentially enriched among different genetic and dietary conditions of the host. This approach faithfully reproduces highly-relevant results from phylogenetic and standard statistical analyses, used to explain the role of the gut microbiome in relation to obesity. This represents a promising proof-of-principle for using functional genomic approaches in the fast growing area of metagenomics, and warrants the availability of a large body of thoroughly tested and theoretically sound methodologies to this exciting new field.}, }
@article {pmid21257745, year = {2011}, author = {Jimenez, RM and Delwart, E and Lupták, A}, title = {Structure-based search reveals hammerhead ribozymes in the human microbiome.}, journal = {The Journal of biological chemistry}, volume = {286}, number = {10}, pages = {7737-7743}, pmid = {21257745}, issn = {1083-351X}, support = {R01 GM094929/GM/NIGMS NIH HHS/United States ; R01 HL083254/HL/NHLBI NIH HHS/United States ; }, mesh = {Base Sequence ; Humans ; Metagenome/*genetics ; Molecular Sequence Data ; RNA, Catalytic/*genetics ; Sequence Alignment ; *Sequence Analysis, RNA ; }, abstract = {Deep sequencing of viral or bacterial nucleic acids monitors the presence and diversity of microbes in select populations and locations. Metagenomic study of mammalian viromes can help trace paths of viral transmissions within or between species. High throughput sequencing of patient and untreated sewage microbiomes showed many sequences with no similarity to genomic sequences of known function or origin. To estimate the distribution of functional RNAs in these microbiomes, we used the hammerhead ribozyme (HHR) motif to search for sequences capable of assuming its three-way junction fold. Although only two of the three possible natural HHR topologies had been known, our analysis revealed highly active ribozymes that terminated in any of the three stems. The most abundant of these are type II HHRs, one of which is the fastest natural cis-acting HHR yet discovered. Altogether, 13 ribozymes were confirmed in vitro, but only one showed sequence similarity to previously described HHRs. Sequences surrounding the ribozymes do not generally show similarity to known genes, except in one case, where a ribozyme is immediately preceded by a bacterial RadC gene. We demonstrate that a structure-based search for a known functional RNA is a powerful tool for analysis of metagenomic datasets, complementing sequence alignments.}, }
@article {pmid21246932, year = {2010}, author = {Power, C and Antony, JM and Ellestad, KK and Deslauriers, A and Bhat, R and Noorbakhsh, F}, title = {The human microbiome in multiple sclerosis: pathogenic or protective constituents?.}, journal = {The Canadian journal of neurological sciences. Le journal canadien des sciences neurologiques}, volume = {37 Suppl 2}, number = {}, pages = {S24-33}, doi = {10.1017/s031716710002240x}, pmid = {21246932}, issn = {0317-1671}, mesh = {Animals ; *Central Nervous System/immunology/microbiology/pathology ; Central Nervous System Viral Diseases/*complications ; Humans ; *Metagenome/genetics ; Models, Biological ; Multiple Sclerosis/genetics/*microbiology/pathology ; }, abstract = {The human microbiome is comprised of commensal and pathogenic microorganisms, which exert diverse effects in close proximity to the site of intection as well as in remote tissues through immune-mediated mechanisms. Multiple infectious agents have been implicated in the pathogenesis of multiple sclerosis (MS) with variable findings depending on the agent, techniques, and disease phenotype. Herein, the contributions of individual infectious agents to MS and their effects on the immune and nervous systems are reviewed, focusing on herpes viruses, coronaviruses, retroviruses, and synchronic infections. While infectious agents are often assumed to be pathogenic, their effects might also be beneficial to the host in the long-term, depending on age and the type of immunogen/pathogen exposure, as proposed by the hygiene hypothesis. The human microbiome has potential impact on future diagnostic and therapeutic issues in MS.}, }
@article {pmid21212162, year = {2011}, author = {Haas, BJ and Gevers, D and Earl, AM and Feldgarden, M and Ward, DV and Giannoukos, G and Ciulla, D and Tabbaa, D and Highlander, SK and Sodergren, E and Methé, B and DeSantis, TZ and ,  and Petrosino, JF and Knight, R and Birren, BW}, title = {Chimeric 16S rRNA sequence formation and detection in Sanger and 454-pyrosequenced PCR amplicons.}, journal = {Genome research}, volume = {21}, number = {3}, pages = {494-504}, pmid = {21212162}, issn = {1549-5469}, support = {U54-HG004969/HG/NHGRI NIH HHS/United States ; U54-HG003079/HG/NHGRI NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; U54 AI084844/AI/NIAID NIH HHS/United States ; U54 HG003273/HG/NHGRI NIH HHS/United States ; U01 HG004866/HG/NHGRI NIH HHS/United States ; N01-AI30071/AI/NIAID NIH HHS/United States ; U54-AI084844/AI/NIAID NIH HHS/United States ; U01-HG004866/HG/NHGRI NIH HHS/United States ; U54 HG003079/HG/NHGRI NIH HHS/United States ; U54-HG004973/HG/NHGRI NIH HHS/United States ; U54-HG003273/HG/NHGRI NIH HHS/United States ; U54 HG004973/HG/NHGRI NIH HHS/United States ; U54-HG004968/HG/NHGRI NIH HHS/United States ; U54 HG004968/HG/NHGRI NIH HHS/United States ; N01AI30071/AI/NIAID NIH HHS/United States ; U54 HG004969/HG/NHGRI NIH HHS/United States ; }, mesh = {*Artifacts ; Bacteria/classification/*genetics ; Base Sequence ; Chimera/genetics ; DNA, Bacterial/analysis/genetics ; DNA, Ribosomal/genetics ; Genomics ; Molecular Sequence Data ; Nucleic Acid Amplification Techniques/methods ; Polymerase Chain Reaction/methods ; RNA, Bacterial/genetics ; RNA, Ribosomal, 16S/*analysis ; Sequence Analysis, DNA/methods ; }, abstract = {Bacterial diversity among environmental samples is commonly assessed with PCR-amplified 16S rRNA gene (16S) sequences. Perceived diversity, however, can be influenced by sample preparation, primer selection, and formation of chimeric 16S amplification products. Chimeras are hybrid products between multiple parent sequences that can be falsely interpreted as novel organisms, thus inflating apparent diversity. We developed a new chimera detection tool called Chimera Slayer (CS). CS detects chimeras with greater sensitivity than previous methods, performs well on short sequences such as those produced by the 454 Life Sciences (Roche) Genome Sequencer, and can scale to large data sets. By benchmarking CS performance against sequences derived from a controlled DNA mixture of known organisms and a simulated chimera set, we provide insights into the factors that affect chimera formation such as sequence abundance, the extent of similarity between 16S genes, and PCR conditions. Chimeras were found to reproducibly form among independent amplifications and contributed to false perceptions of sample diversity and the false identification of novel taxa, with less-abundant species exhibiting chimera rates exceeding 70%. Shotgun metagenomic sequences of our mock community appear to be devoid of 16S chimeras, supporting a role for shotgun metagenomics in validating novel organisms discovered in targeted sequence surveys.}, }
@article {pmid21203913, year = {2010}, author = {Zhu, B and Wang, X and Li, L}, title = {Human gut microbiome: the second genome of human body.}, journal = {Protein &amp; cell}, volume = {1}, number = {8}, pages = {718-725}, pmid = {21203913}, issn = {1674-8018}, mesh = {Animals ; Biota ; Cell Culture Techniques ; Digestive System/immunology/*microbiology ; Digestive System Diseases/microbiology ; Humans ; Immune System ; *Metagenome ; Obesity/microbiology ; Symbiosis ; }, abstract = {The human body is actually a super-organism that is composed of 10 times more microbial cells than our body cells. Metagenomic study of the human microbiome has demonstrated that there are 3.3 million unique genes in human gut, 150 times more genes than our own genome, and the bacterial diversity analysis showed that about 1000 bacterial species are living in our gut and a majority of them belongs to the divisions of Firmicutes and Bacteriodetes. In addition, most people share a core microbiota that comprises 50-100 bacterial species when the frequency of abundance at phylotype level is not considered, and a core microbiome harboring more than 6000 functional gene groups is present in the majority of human gut surveyed till now. Gut bacteria are not only critical for regulating gut metabolism, but also important for host immune system as revealed by animal studies.}, }
@article {pmid21199928, year = {2011}, author = {Liu, A and Fong, A and Becket, E and Yuan, J and Tamae, C and Medrano, L and Maiz, M and Wahba, C and Lee, C and Lee, K and Tran, KP and Yang, H and Hoffman, RM and Salih, A and Miller, JH}, title = {Selective advantage of resistant strains at trace levels of antibiotics: a simple and ultrasensitive color test for detection of antibiotics and genotoxic agents.}, journal = {Antimicrobial agents and chemotherapy}, volume = {55}, number = {3}, pages = {1204-1210}, pmid = {21199928}, issn = {1098-6596}, support = {ES0110875/ES/NIEHS NIH HHS/United States ; }, mesh = {Anti-Bacterial Agents/*pharmacology ; *Color ; Escherichia coli/*drug effects ; Microbial Sensitivity Tests/methods ; }, abstract = {Many studies have examined the evolution of bacterial mutants that are resistant to specific antibiotics, and many of these focus on concentrations at and above the MIC. Here we ask for the minimum concentration at which existing resistant mutants can outgrow sensitive wild-type strains in competition experiments at antibiotic levels significantly below the MIC, and we define a minimum selective concentration (MSC) in Escherichia coli for two antibiotics, which is near 1/5 of the MIC for ciprofloxacin and 1/20 of the MIC for tetracycline. Because of the prevalence of resistant mutants already in the human microbiome, allowable levels of antibiotics to which we are exposed should be below the MSC. Since this concentration often corresponds to low or trace levels of antibiotics, it is helpful to have simple tests to detect such trace levels. We describe a simple ultrasensitive test for detecting the presence of antibiotics and genotoxic agents. The test is based on the use of chromogenic proteins as color markers and the use of single and multiple mutants of Escherichia coli that have greatly increased sensitivity to either a wide range of antibiotics or specific antibiotics, antibiotic families, and genotoxic agents. This test can detect ciprofloxacin at 1/75 of the MIC.}, }
@article {pmid22646824, year = {2011}, author = {Moise, L and Cousens, L and Fueyo, J and De Groot, AS}, title = {Harnessing the power of genomics and immunoinformatics to produce improved vaccines.}, journal = {Expert opinion on drug discovery}, volume = {6}, number = {1}, pages = {9-15}, pmid = {22646824}, issn = {1746-045X}, support = {1U19AI082642/AI/NIAID NIH HHS/United States ; P20RR016457/RR/NCRR NIH HHS/United States ; U19 AI082642-03/AI/NIAID NIH HHS/United States ; U19 AI082642/AI/NIAID NIH HHS/United States ; U19 AI082642-02/AI/NIAID NIH HHS/United States ; }, abstract = {The role of cellular immunity as a mediator of protection against disease is gaining recognition, particularly with regard to the many pathogens for which we presently lack effective vaccines. As a result, there is an ever-increasing need to understand the T-cell populations induced by vaccination and, therefore, T-cell epitopes responsible for triggering their activation. Although the characterization and harnessing of cellular immunity for vaccine development is an active area of research interest, the field still needs to rigorously define T-cell epitope specificities, above all, on a genomic level. New immunoinformatic epitope mapping tools now make it possible to identify pathogen epitopes and perform comparisons against human and microbial genomic data sets. Such information will help to determine whether adaptive immune responses elicited by a vaccine are both pathogen-specific and protective, but not crossreactive against host or host-associated sequences that could jeopardize self-tolerance and/or human microbiome-host homeostasis. Here, we discuss advances in genomics and vaccine design and their relevance to the development of safer, more effective vaccines.}, }
@article {pmid21178459, year = {2010}, author = {Sommer, MO and Church, GM and Dantas, G}, title = {The human microbiome harbors a diverse reservoir of antibiotic resistance genes.}, journal = {Virulence}, volume = {1}, number = {4}, pages = {299-303}, doi = {10.4161/viru.1.4.12010}, pmid = {21178459}, issn = {2150-5608}, mesh = {Anti-Bacterial Agents/pharmacology ; Bacteria/drug effects/genetics ; DNA, Bacterial/analysis/genetics/isolation &amp; purification ; Drug Resistance, Microbial/*genetics ; Feces/microbiology ; *Genes, Bacterial ; Humans ; Metagenome/*genetics ; Metagenomics ; Polymerase Chain Reaction ; Saliva/microbiology ; }, abstract = {The increasing levels of multi-drug resistance in human pathogenic bacteria are compromising our ability to treat infectious disease. Since antibiotic resistance determinants are readily exchanged between bacteria through lateral gene transfer, there is an increasing interest in investigating reservoirs of antibiotic resistance accessible to pathogens. Due to the high likelihood of contact and genetic exchange with pathogens during disease progression, the human microflora warrants special attention as perhaps the most accessible reservoir of resistance genes. Indeed, numerous previous studies have demonstrated substantial antibiotic resistance in cultured isolates from the human microflora. By applying metagenomic functional selections, we recently demonstrated that the functional repertoire of resistance genes in the human microbiome is much more diverse than suggested using previous culture-dependent methods. We showed that many resistance genes from cultured proteobacteria from human fecal samples are identical to resistance genes harbored by human pathogens, providing strong support for recent genetic exchange of this resistance machinery. In contrast, most of the resistance genes we identified with culture independent metagenomic sampling from the same samples were novel when compared to all known genes in public databases. While this clearly demonstrates that the antibiotic resistance reservoir of the large fraction of the human microbiome recalcitrant to culturing is severely under sampled, it may also suggest that barriers exist to lateral gene transfer between these bacteria and readily cultured human pathogens. If we hope to turn the tide against multidrug resistant infections, we must urgently commit to quantitatively characterizing the resistance reservoirs encoded by our diverse human microbiomes, with a particular focus on routes of exchange of these reservoirs with other microbial communities.}, }
@article {pmid21133690, year = {2010}, author = {Alauzet, C and Marchandin, H and Lozniewski, A}, title = {New insights into Prevotella diversity and medical microbiology.}, journal = {Future microbiology}, volume = {5}, number = {11}, pages = {1695-1718}, doi = {10.2217/fmb.10.126}, pmid = {21133690}, issn = {1746-0921}, mesh = {Bacteroidaceae Infections/*microbiology ; Drug Resistance, Bacterial ; *Genetic Variation ; Humans ; *Metagenome ; Prevotella/*classification/genetics/isolation &amp; purification/*pathogenicity ; Virulence ; }, abstract = {In light of recent studies based on cultivation-independent methods, it appears that the diversity of Prevotella in human microbiota is greater than was previously assumed from cultivation-based studies, and that the implication of these bacteria in several human diseases was unrecognized. While some Prevotella taxa were found during opportunistic infections, changes in Prevotella abundance and diversity were discovered during dysbiosis-associated diseases. As member of the microbiota, Prevotella may also be considered as a reservoir for resistance genes. Greater knowledge on Prevotella diversity, as well as new insights into its pathogenic potential and implication in dysbiosis are expected from the use of human microbe identification microarrays, from whole-genome sequence analyse, and from the NIH Human Microbiome Project data. New approaches, including molecular-based methods, could contribute to improve the diagnosis of Prevotella infections.}, }
@article {pmid21124987, year = {2010}, author = {Ferreira, RB and Antunes, LC and Finlay, BB}, title = {Should the human microbiome be considered when developing vaccines?.}, journal = {PLoS pathogens}, volume = {6}, number = {11}, pages = {e1001190}, pmid = {21124987}, issn = {1553-7374}, mesh = {Bacterial Infections/*genetics/immunology/*prevention &amp; control ; *Drug Design ; Humans ; *Metagenome ; Vaccines/*genetics/immunology/*therapeutic use ; }, }
@article {pmid21124952, year = {2010}, author = {Klitgord, N and Segrè, D}, title = {Environments that induce synthetic microbial ecosystems.}, journal = {PLoS computational biology}, volume = {6}, number = {11}, pages = {e1001002}, pmid = {21124952}, issn = {1553-7358}, mesh = {Algorithms ; Culture Media/chemistry/metabolism ; Desulfovibrio vulgaris/metabolism ; *Ecosystem ; Escherichia coli/metabolism ; Methanococcus/metabolism ; *Microbial Interactions ; *Models, Biological ; Saccharomyces cerevisiae/metabolism ; Synthetic Biology/*methods ; Systems Biology/*methods ; }, abstract = {Interactions between microbial species are sometimes mediated by the exchange of small molecules, secreted by one species and metabolized by another. Both one-way (commensal) and two-way (mutualistic) interactions may contribute to complex networks of interdependencies. Understanding these interactions constitutes an open challenge in microbial ecology, with applications ranging from the human microbiome to environmental sustainability. In parallel to natural communities, it is possible to explore interactions in artificial microbial ecosystems, e.g. pairs of genetically engineered mutualistic strains. Here we computationally generate artificial microbial ecosystems without re-engineering the microbes themselves, but rather by predicting their growth on appropriately designed media. We use genome-scale stoichiometric models of metabolism to identify media that can sustain growth for a pair of species, but fail to do so for one or both individual species, thereby inducing putative symbiotic interactions. We first tested our approach on two previously studied mutualistic pairs, and on a pair of highly curated model organisms, showing that our algorithms successfully recapitulate known interactions, robustly predict new ones, and provide novel insight on exchanged molecules. We then applied our method to all possible pairs of seven microbial species, and found that it is always possible to identify putative media that induce commensalism or mutualism. Our analysis also suggests that symbiotic interactions may arise more readily through environmental fluctuations than genetic modifications. We envision that our approach will help generate microbe-microbe interaction maps useful for understanding microbial consortia dynamics and evolution, and for exploring the full potential of natural metabolic pathways for metabolic engineering applications.}, }
@article {pmid21121043, year = {2011}, author = {Moore, JH and Lari, RC and Hill, D and Hibberd, PL and Madan, JC}, title = {Human microbiome visualization using 3D technology.}, journal = {Pacific Symposium on Biocomputing. Pacific Symposium on Biocomputing}, volume = {}, number = {}, pages = {154-164}, doi = {10.1142/9789814335058_0017}, pmid = {21121043}, issn = {2335-6936}, support = {LM009012/LM/NLM NIH HHS/United States ; RR018787/RR/NCRR NIH HHS/United States ; }, mesh = {Computational Biology ; Computer Graphics ; High-Throughput Nucleotide Sequencing/statistics &amp; numerical data ; Humans ; Imaging, Three-Dimensional/statistics &amp; numerical data ; Infant, Newborn ; Infant, Premature ; Metagenome/*genetics ; Sepsis/microbiology ; Software ; }, abstract = {High-throughput sequencing technology has opened the door to the study of the human microbiome and its relationship with health and disease. This is both an opportunity and a significant biocomputing challenge. We present here a 3D visualization methodology and freely-available software package for facilitating the exploration and analysis of high-dimensional human microbiome data. Our visualization approach harnesses the power of commercial video game development engines to provide an interactive medium in the form of a 3D heat map for exploration of microbial species and their relative abundance in different patients. The advantage of this approach is that the third dimension provides additional layers of information that cannot be visualized using a traditional 2D heat map. We demonstrate the usefulness of this visualization approach using microbiome data collected from a sample of premature babies with and without sepsis.}, }
@article {pmid23766284, year = {2010}, author = {Wackett, LP}, title = {Human microbiome: An annotated selection of World Wide Web sites relevant to the topics in Environmental microbiology.}, journal = {Environmental microbiology reports}, volume = {2}, number = {6}, pages = {775-776}, doi = {10.1111/j.1758-2229.2010.00224.x}, pmid = {23766284}, issn = {1758-2229}, }
@article {pmid21106536, year = {2011}, author = {Moore, MD and Cookson, J and Coventry, VK and Sproat, B and Rabe, L and Cranston, RD and McGowan, I and James, W}, title = {Protection of HIV neutralizing aptamers against rectal and vaginal nucleases: implications for RNA-based therapeutics.}, journal = {The Journal of biological chemistry}, volume = {286}, number = {4}, pages = {2526-2535}, pmid = {21106536}, issn = {1083-351X}, support = {G0401610/MRC_/Medical Research Council/United Kingdom ; U01 AI066734/AI/NIAID NIH HHS/United States ; UL1 RR024153/RR/NCRR NIH HHS/United States ; 1 UL1 RR024153/RR/NCRR NIH HHS/United States ; }, mesh = {Antiviral Agents/*pharmacology ; Aptamers, Nucleotide/*pharmacology ; Drug Evaluation, Preclinical ; Female ; HIV Infections/drug therapy/enzymology ; *HIV-1 ; Humans ; Male ; Rectum/*enzymology ; Ribonucleases/*metabolism ; Vagina/*enzymology ; }, abstract = {RNA-based drugs are an emerging class of therapeutics. They have the potential to regulate proteins, chromatin, as well as bind to specific proteins of interest in the form of aptamers. These aptamers are protected from nuclease attack by chemical modifications that enhance their stability for in vivo usage. However, nucleases are ubiquitous, and as we have yet to characterize the entire human microbiome it is likely that many nucleases are yet to be identified. Any novel, unusual enzymes present in vivo might reduce the efficacy of RNA-based therapeutics, even when they are chemically modified. We have previously identified an RNA-based aptamer capable of neutralizing a broad spectrum of clinical HIV-1 isolates and are developing it as a vaginal and rectal microbicide candidate. As a first step we addressed aptamer stability in the milieu of proteins present in these environments. Here we uncover a number of different nucleases that are able to rapidly degrade 2'-F-modified RNA. We demonstrate that the aptamer can be protected from the nuclease(s) present in the vaginal setting, without affecting its antiviral activity, by replacement of key positions with 2'-O-Me-modified nucleotides. Finally, we show that the aptamer can be protected from all nucleases present in both vaginal and rectal compartments using Zn(2+) cations. In conclusion we have derived a stable, antiviral RNA-based aptamer that could form the basis of a pre-exposure microbicide or be a valuable addition to the current tenofovir-based microbicide candidate undergoing clinical trials.}, }
@article {pmid21103066, year = {2010}, author = {Yildirim, S and Yeoman, CJ and Sipos, M and Torralba, M and Wilson, BA and Goldberg, TL and Stumpf, RM and Leigh, SR and White, BA and Nelson, KE}, title = {Characterization of the fecal microbiome from non-human wild primates reveals species specific microbial communities.}, journal = {PloS one}, volume = {5}, number = {11}, pages = {e13963}, pmid = {21103066}, issn = {1932-6203}, mesh = {Animals ; Bacteria/classification/genetics/growth &amp; development ; Base Sequence ; Biodiversity ; Cluster Analysis ; DNA, Bacterial/chemistry/genetics ; *Ecosystem ; Feces/*microbiology ; Gastrointestinal Tract/microbiology ; Genetic Variation ; Humans ; Metagenome/*genetics ; Molecular Sequence Data ; Phylogeny ; Primates/classification/*microbiology ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; Species Specificity ; }, abstract = {BACKGROUND: Host-associated microbes comprise an integral part of animal digestive systems and these interactions have a long evolutionary history. It has been hypothesized that the gastrointestinal microbiome of humans and other non-human primates may have played significant roles in host evolution by facilitating a range of dietary adaptations. We have undertaken a comparative sequencing survey of the gastrointestinal microbiomes of several non-human primate species, with the goal of better understanding how these microbiomes relate to the evolution of non-human primate diversity. Here we present a comparative analysis of gastrointestinal microbial communities from three different species of Old World wild monkeys.<br><br>We analyzed fecal samples from three different wild non-human primate species (black-and-white colobus [Colubus guereza], red colobus [Piliocolobus tephrosceles], and red-tailed guenon [Cercopithecus ascanius]). Three samples from each species were subjected to small subunit rRNA tag pyrosequencing. Firmicutes comprised the vast majority of the phyla in each sample. Other phyla represented were Bacterioidetes, Proteobacteria, Spirochaetes, Actinobacteria, Verrucomicrobia, Lentisphaerae, Tenericutes, Planctomycetes, Fibrobacateres, and TM7. Bray-Curtis similarity analysis of these microbiomes indicated that microbial community composition within the same primate species are more similar to each other than to those of different primate species. Comparison of fecal microbiota from non-human primates with microbiota of human stool samples obtained in previous studies revealed that the gut microbiota of these primates are distinct and reflect host phylogeny.<br><br>CONCLUSION/SIGNIFICANCE: Our analysis provides evidence that the fecal microbiomes of wild primates co-vary with their hosts, and that this is manifested in higher intraspecies similarity among wild primate species, perhaps reflecting species specificity of the microbiome in addition to dietary influences. These results contribute to the limited body of primate microbiome studies and provide a framework for comparative microbiome analysis between human and non-human primates as well as a comparative evolutionary understanding of the human microbiome.}, }
@article {pmid21087892, year = {2011}, author = {Yang, JY and Karr, JR and Watrous, JD and Dorrestein, PC}, title = {Integrating '-omics' and natural product discovery platforms to investigate metabolic exchange in microbiomes.}, journal = {Current opinion in chemical biology}, volume = {15}, number = {1}, pages = {79-87}, pmid = {21087892}, issn = {1879-0402}, support = {R01 GM086283-02/GM/NIGMS NIH HHS/United States ; T32 EB009380/EB/NIBIB NIH HHS/United States ; R01 GM094802/GM/NIGMS NIH HHS/United States ; R01 GM086283-03/GM/NIGMS NIH HHS/United States ; R01 GM086283/GM/NIGMS NIH HHS/United States ; GM094802/GM/NIGMS NIH HHS/United States ; 1 T32 EB009380-01/EB/NIBIB NIH HHS/United States ; R01 GM094802-01/GM/NIGMS NIH HHS/United States ; 5T32GM008326-20/GM/NIGMS NIH HHS/United States ; GM086283/GM/NIGMS NIH HHS/United States ; T32 GM008326/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Biological Products/*analysis/chemistry/metabolism ; Computational Biology ; Genomics/*methods ; Humans ; *Metagenome ; }, abstract = {The microbiome is an abundance of microorganisms within a host (e.g. human microbiome). These microorganisms produce small molecules and metabolites that have been shown to affect and dictate the physiology of an individual. Functional knowledge of these molecules, often produced for communication or defense, will reveal the interplay between microbes and host in health and disease. The vast diversity in structure and function of microbiome-associated small molecules necessitate tools that will utilize multiple '-omics' strategies to understand the interactions within the human microbiome. This review discusses the importance of these investigations and the integration of current '-omics' technologies with tools established in natural product discovery in order to identify and characterize uncharacterized small molecules in the effort towards diagnostic modeling of the human microbiome.}, }
@article {pmid20944220, year = {2010}, author = {Turnbaugh, PJ and Henrissat, B and Gordon, JI}, title = {Viewing the human microbiome through three-dimensional glasses: integrating structural and functional studies to better define the properties of myriad carbohydrate-active enzymes.}, journal = {Acta crystallographica. Section F, Structural biology and crystallization communications}, volume = {66}, number = {Pt 10}, pages = {1261-1264}, pmid = {20944220}, issn = {1744-3091}, support = {P01 DK078669/DK/NIDDK NIH HHS/United States ; R01 DK030292/DK/NIDDK NIH HHS/United States ; DK30292/DK/NIDDK NIH HHS/United States ; R37 DK030292/DK/NIDDK NIH HHS/United States ; DK78669/DK/NIDDK NIH HHS/United States ; }, mesh = {Bacterial Proteins/*chemistry/metabolism ; Carbohydrate Metabolism ; Genomics ; Humans ; *Metagenome ; Protein Conformation ; }, abstract = {Recent studies have provided an unprecedented view of the trillions of microbes associated with the human body. The human microbiome harbors tremendous diversity at multiple levels: the species that colonize each individual and each body habitat; the genes that are found in each organism's genome; the expression of these genes and the interactions and activities of their protein products. The sources of this diversity are wide-ranging and reflect both environmental and host factors. A major challenge moving forward is defining the precise functions of members of various families of proteins represented in our microbiomes, including the highly diverse carbohydrate-active enzymes (CAZymes) involved in numerous biologically important chemical transformations, such as the degradation of complex dietary polysaccharides. Coupling metagenomic analyses to structural genomics initiatives and to biochemical and other functional assays of CAZymes will be essential for determining how these as well as other microbiome-encoded proteins operate to shape the properties of microbial communities and their human hosts.}, }
@article {pmid20924228, year = {2010}, author = {Foxman, B and Goldberg, D}, title = {Why the human microbiome project should motivate epidemiologists to learn ecology.}, journal = {Epidemiology (Cambridge, Mass.)}, volume = {21}, number = {6}, pages = {757-759}, pmid = {20924228}, issn = {1531-5487}, support = {R01 DE014899/DE/NIDCR NIH HHS/United States ; R01 HD038098/HD/NICHD NIH HHS/United States ; R01DE014899/DE/NIDCR NIH HHS/United States ; }, mesh = {*Ecology ; Epidemiology/*trends ; Humans ; *Metagenome ; Sequence Analysis, DNA ; }, }
@article {pmid20833767, year = {2011}, author = {Gootenberg, DB and Turnbaugh, PJ}, title = {Companion animals symposium: humanized animal models of the microbiome.}, journal = {Journal of animal science}, volume = {89}, number = {5}, pages = {1531-1537}, doi = {10.2527/jas.2010-3371}, pmid = {20833767}, issn = {1525-3163}, mesh = {Animals ; Gastrointestinal Tract/*microbiology ; Humans ; Metagenome/*physiology ; Mice ; *Models, Animal ; Rats ; Swine ; Zebrafish ; }, abstract = {Humans and other mammals are colonized by trillions of microorganisms, most of which reside in the gastrointestinal tract, that provide key metabolic capabilities, such as the biosynthesis of vitamins and AA, the degradation of dietary plant polysaccharides, and the metabolism of orally administered therapeutics. Although much progress has been made by studying the human microbiome directly, comparing the human microbiome with that of other animals, and constructing in vitro models of the human gut, there remains a need to develop in vivo models where host, microbial, and environmental parameters can be manipulated. Here, we discuss some of the initial results from a promising method that enables the direct manipulation of microbial community structure, environmental exposures, host genotype, and other factors: the colonization of germ-free animals with complex microbial communities, including those from humans or other animal donors. Analyses of these resulting "humanized" gut microbiomes have begun to reveal 1) that key microbial activities can be transferred from the donor to the recipient animal (e.g., microbial reduction of cholesterol and production of equol), 2) that dietary shifts can affect the composition, gene abundance, and gene expression of the gut microbiome, 3) the succession of the microbial community in infants and ex-germ-free adult animals, and 4) the biogeography of these microbes across the length of gastrointestinal tract. Continued studies of humanized and other intentionally colonized animal models stand to provide new insight into not only the human microbiome, but also the microbiomes of our animal companions.}, }
@article {pmid20807838, year = {2010}, author = {Sahota, G and Stormo, GD}, title = {Novel sequence-based method for identifying transcription factor binding sites in prokaryotic genomes.}, journal = {Bioinformatics (Oxford, England)}, volume = {26}, number = {21}, pages = {2672-2677}, pmid = {20807838}, issn = {1367-4811}, support = {T32 GM07200/GM/NIGMS NIH HHS/United States ; T32 GM008802/GM/NIGMS NIH HHS/United States ; T32 GM007200/GM/NIGMS NIH HHS/United States ; R01 HG000249/HG/NHGRI NIH HHS/United States ; R01 HG00249/HG/NHGRI NIH HHS/United States ; }, mesh = {Binding Sites ; Computational Biology/methods ; *Genome ; *Promoter Regions, Genetic ; Sequence Analysis, DNA/*methods ; Transcription Factors/*chemistry/*metabolism ; }, abstract = {MOTIVATION: Computational techniques for microbial genomic sequence analysis are becoming increasingly important. With next-generation sequencing technology and the human microbiome project underway, current sequencing capacity is significantly greater than the speed at which organisms of interest can be studied experimentally. Most related computational work has been focused on sequence assembly, gene annotation and metabolic network reconstruction. We have developed a method that will primarily use available sequence data in order to determine prokaryotic transcription factor (TF) binding specificities.<br><br>RESULTS: Specificity determining residues (critical residues) were identified from crystal structures of DNA-protein complexes and TFs with the same critical residues were grouped into specificity classes. The putative binding regions for each class were defined as the set of promoters for each TF itself (autoregulatory) and the immediately upstream and downstream operons. MEME was used to find putative motifs within each separate class. Tests on the LacI and TetR TF families, using RegulonDB annotated sites, showed the sensitivity of prediction 86% and 80%, respectively.<br><br>AVAILABILITY: http://ural.wustl.edu/&#x223c;gsahota/HTHmotif/}, }
@article {pmid20805407, year = {2010}, author = {Robinson, CJ and Bohannan, BJ and Young, VB}, title = {From structure to function: the ecology of host-associated microbial communities.}, journal = {Microbiology and molecular biology reviews : MMBR}, volume = {74}, number = {3}, pages = {453-476}, pmid = {20805407}, issn = {1098-5557}, support = {R01 DK070875/DK/NIDDK NIH HHS/United States ; R01DK070875-03S1/DK/NIDDK NIH HHS/United States ; R01DK070875/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Bacterial Infections/metabolism ; Host-Pathogen Interactions ; Humans ; Metagenome/*physiology ; }, abstract = {In the past several years, we have witnessed an increased interest in understanding the structure and function of the indigenous microbiota that inhabits the human body. It is hoped that this will yield novel insight into the role of these complex microbial communities in human health and disease. What is less appreciated is that this recent activity owes a great deal to the pioneering efforts of microbial ecologists who have been studying communities in non-host-associated environments. Interactions between environmental microbiologists and human microbiota researchers have already contributed to advances in our understanding of the human microbiome. We review the work that has led to these recent advances and illustrate some of the possible future directions for continued collaboration between these groups of researchers. We discuss how the application of ecological theory to the human-associated microbiota can lead us past descriptions of community structure and toward an understanding of the functions of the human microbiota. Such an approach may lead to a shift in the prevention and treatment of human diseases that involves conservation or restoration of the normal community structure and function of the host-associated microbiota.}, }
@article {pmid20705661, year = {2010}, author = {Jernberg, C and Löfmark, S and Edlund, C and Jansson, JK}, title = {Long-term impacts of antibiotic exposure on the human intestinal microbiota.}, journal = {Microbiology (Reading, England)}, volume = {156}, number = {Pt 11}, pages = {3216-3223}, doi = {10.1099/mic.0.040618-0}, pmid = {20705661}, issn = {1465-2080}, mesh = {Anti-Bacterial Agents/*pharmacology ; Bacteria/*drug effects/growth &amp; development ; *Drug Resistance, Bacterial ; Humans ; Intestines/*microbiology ; *Metagenome ; Time Factors ; }, abstract = {Although it is known that antibiotics have short-term impacts on the human microbiome, recent evidence demonstrates that the impacts of some antibiotics remain for extended periods of time. In addition, antibiotic-resistant strains can persist in the human host environment in the absence of selective pressure. Both molecular- and cultivation-based approaches have revealed ecological disturbances in the microbiota after antibiotic administration, in particular for specific members of the bacterial community that are susceptible or alternatively resistant to the antibiotic in question. A disturbing consequence of antibiotic treatment has been the long-term persistence of antibiotic resistance genes, for example in the human gut. These data warrant use of prudence in the administration of antibiotics that could aggravate the growing battle with emerging antibiotic-resistant pathogenic strains.}, }
@article {pmid20624719, year = {2010}, author = {Chen, T and Yu, WH and Izard, J and Baranova, OV and Lakshmanan, A and Dewhirst, FE}, title = {The Human Oral Microbiome Database: a web accessible resource for investigating oral microbe taxonomic and genomic information.}, journal = {Database : the journal of biological databases and curation}, volume = {2010}, number = {}, pages = {baq013}, pmid = {20624719}, issn = {1758-0463}, support = {R21 DE017106-01A1/DE/NIDCR NIH HHS/United States ; DE017106/DE/NIDCR NIH HHS/United States ; R21 DE017106-02/DE/NIDCR NIH HHS/United States ; U01 DE016937/DE/NIDCR NIH HHS/United States ; R21 DE017106/DE/NIDCR NIH HHS/United States ; DE016937/DE/NIDCR NIH HHS/United States ; }, mesh = {Bacteria/classification/genetics/isolation &amp; purification ; Computers ; *Databases, Genetic ; Genome, Bacterial ; Humans ; Internet ; Metagenome/*genetics ; Metagenomics ; Mouth/*microbiology ; Phenotype ; RNA, Bacterial/genetics ; RNA, Ribosomal, 16S/genetics ; Sequence Alignment ; Software ; }, abstract = {The human oral microbiome is the most studied human microflora, but 53% of the species have not yet been validly named and 35% remain uncultivated. The uncultivated taxa are known primarily from 16S rRNA sequence information. Sequence information tied solely to obscure isolate or clone numbers, and usually lacking accurate phylogenetic placement, is a major impediment to working with human oral microbiome data. The goal of creating the Human Oral Microbiome Database (HOMD) is to provide the scientific community with a body site-specific comprehensive database for the more than 600 prokaryote species that are present in the human oral cavity based on a curated 16S rRNA gene-based provisional naming scheme. Currently, two primary types of information are provided in HOMD--taxonomic and genomic. Named oral species and taxa identified from 16S rRNA gene sequence analysis of oral isolates and cloning studies were placed into defined 16S rRNA phylotypes and each given unique Human Oral Taxon (HOT) number. The HOT interlinks phenotypic, phylogenetic, genomic, clinical and bibliographic information for each taxon. A BLAST search tool is provided to match user 16S rRNA gene sequences to a curated, full length, 16S rRNA gene reference data set. For genomic analysis, HOMD provides comprehensive set of analysis tools and maintains frequently updated annotations for all the human oral microbial genomes that have been sequenced and publicly released. Oral bacterial genome sequences, determined as part of the Human Microbiome Project, are being added to the HOMD as they become available. We provide HOMD as a conceptual model for the presentation of microbiome data for other human body sites. Database URL: http://www.homd.org.}, }
@article {pmid20566857, year = {2010}, author = {Dominguez-Bello, MG and Costello, EK and Contreras, M and Magris, M and Hidalgo, G and Fierer, N and Knight, R}, title = {Delivery mode shapes the acquisition and structure of the initial microbiota across multiple body habitats in newborns.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {107}, number = {26}, pages = {11971-11975}, pmid = {20566857}, issn = {1091-6490}, support = {R01 HG004872/HG/NHGRI NIH HHS/United States ; R01HG004872/HG/NHGRI NIH HHS/United States ; }, mesh = {Adult ; Bacteria/classification/genetics/*isolation &amp; purification ; Base Sequence ; Cesarean Section ; DNA Primers/genetics ; Delivery, Obstetric/*methods ; Ecosystem ; Female ; Humans ; *Infant, Newborn ; Male ; *Metagenome/genetics ; Mouth Mucosa/microbiology ; Nasopharynx/microbiology ; Pregnancy ; RNA, Bacterial/genetics/isolation &amp; purification ; RNA, Ribosomal, 16S/genetics/isolation &amp; purification ; Skin/microbiology ; Vagina/microbiology ; Venezuela ; Young Adult ; }, abstract = {Upon delivery, the neonate is exposed for the first time to a wide array of microbes from a variety of sources, including maternal bacteria. Although prior studies have suggested that delivery mode shapes the microbiota's establishment and, subsequently, its role in child health, most researchers have focused on specific bacterial taxa or on a single body habitat, the gut. Thus, the initiation stage of human microbiome development remains obscure. The goal of the present study was to obtain a community-wide perspective on the influence of delivery mode and body habitat on the neonate's first microbiota. We used multiplexed 16S rRNA gene pyrosequencing to characterize bacterial communities from mothers and their newborn babies, four born vaginally and six born via Cesarean section. Mothers' skin, oral mucosa, and vagina were sampled 1 h before delivery, and neonates' skin, oral mucosa, and nasopharyngeal aspirate were sampled <5 min, and meconium <24 h, after delivery. We found that in direct contrast to the highly differentiated communities of their mothers, neonates harbored bacterial communities that were undifferentiated across multiple body habitats, regardless of delivery mode. Our results also show that vaginally delivered infants acquired bacterial communities resembling their own mother's vaginal microbiota, dominated by Lactobacillus, Prevotella, or Sneathia spp., and C-section infants harbored bacterial communities similar to those found on the skin surface, dominated by Staphylococcus, Corynebacterium, and Propionibacterium spp. These findings establish an important baseline for studies tracking the human microbiome's successional development in different body habitats following different delivery modes, and their associated effects on infant health.}, }
@article {pmid20491067, year = {2010}, author = {Naqvi, A and Rangwala, H and Spear, G and Gillevet, P}, title = {Analysis of multitag pyrosequence data from human cervical lavage samples.}, journal = {Chemistry &amp; biodiversity}, volume = {7}, number = {5}, pages = {1076-1085}, doi = {10.1002/cbdv.200900321}, pmid = {20491067}, issn = {1612-1880}, mesh = {Bacteria/*classification/genetics/isolation &amp; purification ; Cervix Uteri ; Cluster Analysis ; Female ; HIV Infections/complications ; Humans ; *Metagenome ; RNA, Ribosomal, 16S/genetics ; *Sequence Analysis, DNA ; Therapeutic Irrigation ; Vaginosis, Bacterial/complications/*microbiology ; }, abstract = {We have been using the Roche GS-FLX sequencing platform to produce tens of thousands of sequencing reads from samples of both bacterial communities (microbiome) and fungal communities (mycobiome) of stool, gut mucosa, vaginal washes, and oral washes from a large number of subjects. This vast volume of data from diverse sources has necessitated the development of an analysis pipeline in order to systematically and rapidly identify the taxa within the samples and to correlate the sample data with clinical and environmental features. Specifically, we have developed automated analytical tools for data tracking, taxonomical analysis, and feature clustering of bacteria in the human microbiome and demonstrate the pipeline using Cervical Vaginal Lavage (CVL) samples. This analysis pipeline will not only provide insight to our specific CVL dataset, but is applicable to other microbiome samples and will ultimately broaden our understanding of how the microbiome influences human health.}, }
@article {pmid20491064, year = {2010}, author = {Gillevet, P and Sikaroodi, M and Keshavarzian, A and Mutlu, EA}, title = {Quantitative assessment of the human gut microbiome using multitag pyrosequencing.}, journal = {Chemistry &amp; biodiversity}, volume = {7}, number = {5}, pages = {1065-1075}, pmid = {20491064}, issn = {1612-1880}, support = {R01 AA013745/AA/NIAAA NIH HHS/United States ; R21 AT001628/AT/NCCIH NIH HHS/United States ; R43 DK074275/DK/NIDDK NIH HHS/United States ; RC2 AA019405/AA/NIAAA NIH HHS/United States ; }, mesh = {Colitis, Ulcerative/genetics/metabolism/microbiology ; Crohn Disease/genetics/metabolism/microbiology ; Gastrointestinal Tract/metabolism/*microbiology ; Humans ; Inflammatory Bowel Diseases/genetics/metabolism/microbiology ; Intestinal Mucosa/metabolism ; *Metagenome ; Polymerase Chain Reaction ; RNA, Ribosomal, 16S/genetics ; *Sequence Analysis, DNA ; }, abstract = {Recent advances in molecular techniques have now made it possible to interrogate the human microbiome in depth to better understand the interactions with the host organism and its role in diseases. We now report the utility of Length Heterogeneity Polymerase Chain Reaction (LH-PCR) to survey samples and a proprietary Multitagged Pyrosequencing (MTPS) methodology to interrogate the gut microbiome in healthy and disease states. We present an overview of our studies demonstrating the application of these molecular-biology techniques to an example disease state such as Inflammatory Bowel Disease (IBD). The findings show that there is a core mucosal bacterial microbiome (i.e., a mucosal biofilm) that is distinct from the luminal microbiome in health, and that the mucosal microbiome appears to be dysbiotic in IBD. We propose that the mucosal microbiome forms a synergistic and stable interaction with the host immune system, while the lumen microbiome varies based on diet or other environmental factors. We define this composite ecosystem of the human microbiome and human host as the Human Metabiome.}, }
@article {pmid20489017, year = {2010}, author = {,  and Nelson, KE and Weinstock, GM and Highlander, SK and Worley, KC and Creasy, HH and Wortman, JR and Rusch, DB and Mitreva, M and Sodergren, E and Chinwalla, AT and Feldgarden, M and Gevers, D and Haas, BJ and Madupu, R and Ward, DV and Birren, BW and Gibbs, RA and Methe, B and Petrosino, JF and Strausberg, RL and Sutton, GG and White, OR and Wilson, RK and Durkin, S and Giglio, MG and Gujja, S and Howarth, C and Kodira, CD and Kyrpides, N and Mehta, T and Muzny, DM and Pearson, M and Pepin, K and Pati, A and Qin, X and Yandava, C and Zeng, Q and Zhang, L and Berlin, AM and Chen, L and Hepburn, TA and Johnson, J and McCorrison, J and Miller, J and Minx, P and Nusbaum, C and Russ, C and Sykes, SM and Tomlinson, CM and Young, S and Warren, WC and Badger, J and Crabtree, J and Markowitz, VM and Orvis, J and Cree, A and Ferriera, S and Fulton, LL and Fulton, RS and Gillis, M and Hemphill, LD and Joshi, V and Kovar, C and Torralba, M and Wetterstrand, KA and Abouellleil, A and Wollam, AM and Buhay, CJ and Ding, Y and Dugan, S and FitzGerald, MG and Holder, M and Hostetler, J and Clifton, SW and Allen-Vercoe, E and Earl, AM and Farmer, CN and Liolios, K and Surette, MG and Xu, Q and Pohl, C and Wilczek-Boney, K and Zhu, D}, title = {A catalog of reference genomes from the human microbiome.}, journal = {Science (New York, N.Y.)}, volume = {328}, number = {5981}, pages = {994-999}, pmid = {20489017}, issn = {1095-9203}, support = {U54-HG004969/HG/NHGRI NIH HHS/United States ; U54-HG003079/HG/NHGRI NIH HHS/United States ; U54 HG004973-02/HG/NHGRI NIH HHS/United States ; U54 HG003273-04S1/HG/NHGRI NIH HHS/United States ; /CAPMC/CIHR/Canada ; U54 HG003273/HG/NHGRI NIH HHS/United States ; U54 HG003273-05S2/HG/NHGRI NIH HHS/United States ; U54 HG003273-08/HG/NHGRI NIH HHS/United States ; U54 HG003273-04/HG/NHGRI NIH HHS/United States ; U54 HG003273-06S1/HG/NHGRI NIH HHS/United States ; U54-AI084844/AI/NIAID NIH HHS/United States ; U54 HG003079/HG/NHGRI NIH HHS/United States ; U54 HG003273-06S2/HG/NHGRI NIH HHS/United States ; U54-HG003273/HG/NHGRI NIH HHS/United States ; U54 HG004973/HG/NHGRI NIH HHS/United States ; U54 HG003067/HG/NHGRI NIH HHS/United States ; U54 HG003273-05S1/HG/NHGRI NIH HHS/United States ; U54 AI084844/AI/NIAID NIH HHS/United States ; U54 HG003273-05/HG/NHGRI NIH HHS/United States ; U54 HG004973-01/HG/NHGRI NIH HHS/United States ; U54-HG004968/HG/NHGRI NIH HHS/United States ; U54 HG004968/HG/NHGRI NIH HHS/United States ; U54 HG004969/HG/NHGRI NIH HHS/United States ; N01 AI30071/AI/NIAID NIH HHS/United States ; U54 HG003273-07/HG/NHGRI NIH HHS/United States ; U54-HG004973/HG/NHGRI NIH HHS/United States ; HHSN272200900017C/AI/NIAID NIH HHS/United States ; U54 HG003273-06/HG/NHGRI NIH HHS/United States ; N01 AI030071/AI/NIAID NIH HHS/United States ; }, mesh = {Bacteria/classification/genetics ; Bacterial Proteins/chemistry/genetics ; Biodiversity ; Computational Biology ; Databases, Genetic ; Gastrointestinal Tract/microbiology ; Genes, Bacterial ; Genetic Variation ; Genome, Archaeal ; *Genome, Bacterial ; Humans ; Metagenome/*genetics ; Metagenomics/methods/standards ; Mouth/microbiology ; Peptides/chemistry/genetics ; Phylogeny ; Respiratory System/microbiology ; *Sequence Analysis, DNA/standards ; Skin/microbiology ; Urogenital System/microbiology ; }, abstract = {The human microbiome refers to the community of microorganisms, including prokaryotes, viruses, and microbial eukaryotes, that populate the human body. The National Institutes of Health launched an initiative that focuses on describing the diversity of microbial species that are associated with health and disease. The first phase of this initiative includes the sequencing of hundreds of microbial reference genomes, coupled to metagenomic sequencing from multiple body sites. Here we present results from an initial reference genome sequencing of 178 microbial genomes. From 547,968 predicted polypeptides that correspond to the gene complement of these strains, previously unidentified ("novel") polypeptides that had both unmasked sequence length greater than 100 amino acids and no BLASTP match to any nonreference entry in the nonredundant subset were defined. This analysis resulted in a set of 30,867 polypeptides, of which 29,987 (approximately 97%) were unique. In addition, this set of microbial genomes allows for approximately 40% of random sequences from the microbiome of the gastrointestinal tract to be associated with organisms based on the match criteria used. Insights into pan-genome analysis suggest that we are still far from saturating microbial species genetic data sets. In addition, the associated metrics and standards used by our group for quality assurance are presented.}, }
@article {pmid20471127, year = {2010}, author = {Candela, M and Maccaferri, S and Turroni, S and Carnevali, P and Brigidi, P}, title = {Functional intestinal microbiome, new frontiers in prebiotic design.}, journal = {International journal of food microbiology}, volume = {140}, number = {2-3}, pages = {93-101}, doi = {10.1016/j.ijfoodmicro.2010.04.017}, pmid = {20471127}, issn = {1879-3460}, mesh = {Animals ; Bacteria/genetics/*metabolism ; Humans ; Intestinal Mucosa/metabolism ; Intestines/*microbiology ; *Metagenome ; Prebiotics/*analysis ; }, abstract = {In this review we focus on the revision of the prebiotic concept in the context of the new metagenomic era. Functional metagenomic data provided by the Human Microbiome Project are revolutionizing the view of the symbiotic relationship between the intestinal microbiota and the human host. A deeper knowledge of the mechanisms that govern the dynamic interplay between diet, intestinal microbiota and host nutrition opens the way to better information on the prebiotic structure-function relationships, tailoring prebiotic formula into specific health attributes. On the other hand, functional genomic studies of the sourdough microbial communities allow to scan the environmental variability to identify novel metabolic traits for the biosynthesis of new potential prebiotic molecules. The integration of the functional analyses provided by the massive sequencing of bacterial genomes and metagenomes will allow the rational production of a desired prebiotic molecule with specific functional properties.}, }
@article {pmid20441597, year = {2010}, author = {Kuczynski, J and Costello, EK and Nemergut, DR and Zaneveld, J and Lauber, CL and Knights, D and Koren, O and Fierer, N and Kelley, ST and Ley, RE and Gordon, JI and Knight, R}, title = {Direct sequencing of the human microbiome readily reveals community differences.}, journal = {Genome biology}, volume = {11}, number = {5}, pages = {210}, pmid = {20441597}, issn = {1474-760X}, support = {T32 GM008759/GM/NIGMS NIH HHS/United States ; T32 GM142607/GM/NIGMS NIH HHS/United States ; }, mesh = {Bacteria/*genetics ; Base Sequence ; Disease ; Ecosystem ; Humans ; Metagenome/*genetics ; Molecular Sequence Data ; Sequence Analysis, DNA/*methods ; }, abstract = {Culture-independent studies of human microbiota by direct genomic sequencing reveal quite distinct differences among communities, indicating that improved sequencing capacity can be most wisely utilized to study more samples, rather than more sequences per sample.}, }
@article {pmid20418441, year = {2010}, author = {Pei, AY and Oberdorf, WE and Nossa, CW and Agarwal, A and Chokshi, P and Gerz, EA and Jin, Z and Lee, P and Yang, L and Poles, M and Brown, SM and Sotero, S and Desantis, T and Brodie, E and Nelson, K and Pei, Z}, title = {Diversity of 16S rRNA genes within individual prokaryotic genomes.}, journal = {Applied and environmental microbiology}, volume = {76}, number = {12}, pages = {3886-3897}, pmid = {20418441}, issn = {1098-5336}, support = {R01 AI063477/AI/NIAID NIH HHS/United States ; UH2 CA140233/CA/NCI NIH HHS/United States ; R01AI063477/AI/NIAID NIH HHS/United States ; UH2CA140233/CA/NCI NIH HHS/United States ; }, mesh = {Genes, rRNA/*genetics ; *Genome, Archaeal ; *Genome, Bacterial ; *Polymorphism, Genetic ; RNA, Ribosomal, 16S/*genetics ; }, abstract = {Analysis of intragenomic variation of 16S rRNA genes is a unique approach to examining the concept of ribosomal constraints on rRNA genes; the degree of variation is an important parameter to consider for estimation of the diversity of a complex microbiome in the recently initiated Human Microbiome Project (http://nihroadmap.nih.gov/hmp). The current GenBank database has a collection of 883 prokaryotic genomes representing 568 unique species, of which 425 species contained 2 to 15 copies of 16S rRNA genes per genome (2.22 +/- 0.81). Sequence diversity among the 16S rRNA genes in a genome was found in 235 species (from 0.06% to 20.38%; 0.55% +/- 1.46%). Compared with the 16S rRNA-based threshold for operational definition of species (1 to 1.3% diversity), the diversity was borderline (between 1% and 1.3%) in 10 species and >1.3% in 14 species. The diversified 16S rRNA genes in Haloarcula marismortui (diversity, 5.63%) and Thermoanaerobacter tengcongensis (6.70%) were highly conserved at the 2 degrees structure level, while the diversified gene in B. afzelii (20.38%) appears to be a pseudogene. The diversified genes in the remaining 21 species were also conserved, except for a truncated 16S rRNA gene in "Candidatus Protochlamydia amoebophila." Thus, this survey of intragenomic diversity of 16S rRNA genes provides strong evidence supporting the theory of ribosomal constraint. Taxonomic classification using the 16S rRNA-based operational threshold could misclassify a number of species into more than one species, leading to an overestimation of the diversity of a complex microbiome. This phenomenon is especially seen in 7 bacterial species associated with the human microbiome or diseases.}, }
@article {pmid20360554, year = {2010}, author = {Blaser, MJ}, title = {Harnessing the power of the human microbiome.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {107}, number = {14}, pages = {6125-6126}, pmid = {20360554}, issn = {1091-6490}, support = {R01 GM063270/GM/NIGMS NIH HHS/United States ; UH2 AR057506/AR/NIAMS NIH HHS/United States ; R01GM63270/GM/NIGMS NIH HHS/United States ; UH2-AR057506/AR/NIAMS NIH HHS/United States ; }, mesh = {Fingers/*microbiology ; Humans ; *Metagenome ; Skin/*microbiology ; }, }
@article {pmid20337064, year = {2010}, author = {Xue, J and Xiao, LY and Zhou, XD}, title = {[The latest progress in studies of human oral microbiome].}, journal = {Hua xi kou qiang yi xue za zhi = Huaxi kouqiang yixue zazhi = West China journal of stomatology}, volume = {28}, number = {1}, pages = {5-8}, pmid = {20337064}, issn = {1000-1182}, mesh = {Humans ; *Metagenome ; *Microbiota ; Mouth/*microbiology ; }, abstract = {With the successful implementation of Human Genome Project, more and more scientists started to pay attention on the second genome of human body: Microbiome. This paper will briefly introduce the latest developments of the Human Microbiome Project, the human oral microbiome research, and new technologies of microbial gene research.}, }
@article {pmid23100817, year = {2010}, author = {Rajendhran, J and Gunasekaran, P}, title = {Human microbiomics.}, journal = {Indian journal of microbiology}, volume = {50}, number = {1}, pages = {109-112}, pmid = {23100817}, issn = {0046-8991}, abstract = {The sequencing of the human genome has driven the study of human biology in a significant way and enabled the genome-wide study to elucidate the molecular basis of complex human diseases. Recently, the role of microbiota on human physiology and health has received much attention. The influence of gut microbiome (the collective genomes of the gut microbiota) in obesity has been demonstrated, which may pave the way for new prophylactic and therapeutic strategies such as bacteriotherapy. The significance and recent understandings in the area of "human microbiomics" are discussed here.}, }
@article {pmid20176062, year = {2010}, author = {Zhao, L and Shen, J}, title = {Whole-body systems approaches for gut microbiota-targeted, preventive healthcare.}, journal = {Journal of biotechnology}, volume = {149}, number = {3}, pages = {183-190}, doi = {10.1016/j.jbiotec.2010.02.008}, pmid = {20176062}, issn = {1873-4863}, mesh = {Chronic Disease ; Humans ; Intestinal Mucosa/metabolism ; Intestines/immunology/*microbiology ; Metabolome ; *Preventive Medicine ; }, abstract = {Humans are superorganisms with two genomes that dictate phenotype, the genetically inherited human genome (25,000 genes) and the environmentally acquired human microbiome (over 1 million genes). The two genomes must work in harmonious integration as a hologenome to maintain health. Nutrition plays a crucial role in directly modulating our microbiomes and health phenotypes. Poorly balanced diets can turn the gut microbiome from a partner for health to a "pathogen" in chronic diseases, e.g. accumulating evidence supports the new hypothesis that obesity and related metabolic diseases develop because of low-grade, systemic and chronic inflammation induced by diet-disrupted gut microbiota. Due to the tight integration of gut microbiota into human global metabolism, molecular profiling of urine metabolites can provide a new window for reflecting physiological functions of gut microbiomes. Changes of gut microbiota and urine metabolites can thus be employed as new systems approaches for quantitative assessment and monitoring of health at the whole-body level with the advantage of measuring human health based on the results of interactions between the two genomes and the environment rather than just host genomic information. Large-scale population-based studies in conjunction with these whole-body level systems methods will generate pre-disease biomarkers with predictive power, thus making preventive health management of populations with rapidly changing disease spectrums possible through re-engineering of the imbalanced gut microbiomes with specially designed foods/diets.}, }
@article {pmid19968883, year = {2009}, author = {Aziz, RK}, title = {A hundred-year-old insight into the gut microbiome!.}, journal = {Gut pathogens}, volume = {1}, number = {1}, pages = {21}, pmid = {19968883}, issn = {1757-4749}, abstract = {As the National Institutes of Health-funded Human Microbiome Project enters its second phase, and as a major part of this project focuses on the human gut microbiome and its effects on human health, it might help us to travel a century back in time and examine how microbiologists dealt with microbiome-related challenges similar to those of the 21st century using the tools of their time. An article by Arthur I. Kendall, published in The Journal of Biological Chemistry in November 1909 (Some observations on the study of the intestinal bacteria J Biol Chem 1909, 6:499-507), offers a visionary insight into many of today's hot research questions.}, }
@article {pmid19961416, year = {2009}, author = {Beloborodova, NV and Khodakova, AS and Bairamov, IT and Olenin, AY}, title = {Microbial origin of phenylcarboxylic acids in the human body.}, journal = {Biochemistry. Biokhimiia}, volume = {74}, number = {12}, pages = {1350-1355}, doi = {10.1134/s0006297909120086}, pmid = {19961416}, issn = {1608-3040}, mesh = {Escherichia coli/metabolism ; Humans ; Klebsiella pneumoniae/metabolism ; Phenylacetates/*analysis/blood ; Phenylpropionates/*analysis ; Sepsis/microbiology ; Staphylococcus aureus/metabolism ; }, abstract = {In previous studies we demonstrated increased amounts of phenylcarboxylic acids (PCA) in serum of patients with sepsis. This observation prompted the present study of the ability of the human microbiome bacteria to produce PCA in vitro. PCA were detected in culture media by gas chromatography-mass spectrometry. Increased amounts of phenyllactic and p-hydroxyphenyllactic acids were produced by Klebsiella pneumonia, Escherichia coli, and Staphylococcus aureus. Certain strict anaerobes (bifidobacteria, lactobacteria, eubacteria) have also been found to actively produce these PCA, but these bacteria are not etiologically linked to sepsis. Thus our results demonstrate the ability of sepsis-related bacteria to produce PCA and provide experimental support for the theory that the accumulation of PCA in the blood of patients with sepsis results from microbial degradation of phenylalanine and tyrosine.}, }
@article {pmid19901833, year = {2010}, author = {Ley, RE}, title = {Obesity and the human microbiome.}, journal = {Current opinion in gastroenterology}, volume = {26}, number = {1}, pages = {5-11}, doi = {10.1097/MOG.0b013e328333d751}, pmid = {19901833}, issn = {1531-7056}, mesh = {Animals ; Body Mass Index ; Dietary Fats/metabolism ; Energy Metabolism/genetics ; Gastroenteritis/genetics/physiopathology ; Gastrointestinal Tract/metabolism/*microbiology ; Genetic Predisposition to Disease ; Humans ; Insulin Resistance/*genetics ; Metagenome/*genetics/physiology ; Mice ; Obesity/*genetics/metabolism ; Rats ; Risk Assessment ; Sensitivity and Specificity ; Swine ; }, abstract = {PURPOSE OF REVIEW: Obesity was once rare, but the last few decades have seen a rapid expansion of the proportion of obese individuals worldwide. Recent work has shown obesity to be associated with a shift in the representation of the dominant phyla of bacteria in the gut, both in humans and animal models. This review summarizes the latest research into the association between microbial ecology and host adiposity, and the mechanisms by which microbes in the gut may mediate host metabolism in the context of obesity.<br><br>RECENT FINDINGS: Studies of the effect of excess body fat on the abundances of different bacteria taxa in the gut generally show alterations in the gastrointestinal microbiota, and changes during weight loss. The gastrointestinal microbiota have been shown to impact insulin resistance, inflammation, and adiposity via interactions with epithelial and endocrine cells.<br><br>SUMMARY: Large-scale alterations of the gut microbiota and its microbiome (gene content) are associated with obesity and are responsive to weight loss. Gut microbes can impact host metabolism via signaling pathways in the gut, with effects on inflammation, insulin resistance, and deposition of energy in fat stores. Restoration of the gut microbiota to a healthy state may ameliorate the conditions associated with obesity and help maintain a healthy weight.}, }
@article {pmid19819907, year = {2009}, author = {,  and Peterson, J and Garges, S and Giovanni, M and McInnes, P and Wang, L and Schloss, JA and Bonazzi, V and McEwen, JE and Wetterstrand, KA and Deal, C and Baker, CC and Di Francesco, V and Howcroft, TK and Karp, RW and Lunsford, RD and Wellington, CR and Belachew, T and Wright, M and Giblin, C and David, H and Mills, M and Salomon, R and Mullins, C and Akolkar, B and Begg, L and Davis, C and Grandison, L and Humble, M and Khalsa, J and Little, AR and Peavy, H and Pontzer, C and Portnoy, M and Sayre, MH and Starke-Reed, P and Zakhari, S and Read, J and Watson, B and Guyer, M}, title = {The NIH Human Microbiome Project.}, journal = {Genome research}, volume = {19}, number = {12}, pages = {2317-2323}, pmid = {19819907}, issn = {1549-5469}, mesh = {*Bacteria/classification/genetics/isolation &amp; purification ; Female ; Gastrointestinal Tract/*microbiology ; Humans ; Metagenome/*genetics ; Mouth/*microbiology ; National Health Programs ; *National Institutes of Health (U.S.) ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; Skin/*microbiology ; United States ; Vagina/*microbiology ; }, abstract = {The Human Microbiome Project (HMP), funded as an initiative of the NIH Roadmap for Biomedical Research (http://nihroadmap.nih.gov), is a multi-component community resource. The goals of the HMP are: (1) to take advantage of new, high-throughput technologies to characterize the human microbiome more fully by studying samples from multiple body sites from each of at least 250 "normal" volunteers; (2) to determine whether there are associations between changes in the microbiome and health/disease by studying several different medical conditions; and (3) to provide both a standardized data resource and new technological approaches to enable such studies to be undertaken broadly in the scientific community. The ethical, legal, and social implications of such research are being systematically studied as well. The ultimate objective of the HMP is to demonstrate that there are opportunities to improve human health through monitoring or manipulation of the human microbiome. The history and implementation of this new program are described here.}, }
@article {pmid19815760, year = {2009}, author = {Chain, PS and Grafham, DV and Fulton, RS and Fitzgerald, MG and Hostetler, J and Muzny, D and Ali, J and Birren, B and Bruce, DC and Buhay, C and Cole, JR and Ding, Y and Dugan, S and Field, D and Garrity, GM and Gibbs, R and Graves, T and Han, CS and Harrison, SH and Highlander, S and Hugenholtz, P and Khouri, HM and Kodira, CD and Kolker, E and Kyrpides, NC and Lang, D and Lapidus, A and Malfatti, SA and Markowitz, V and Metha, T and Nelson, KE and Parkhill, J and Pitluck, S and Qin, X and Read, TD and Schmutz, J and Sozhamannan, S and Sterk, P and Strausberg, RL and Sutton, G and Thomson, NR and Tiedje, JM and Weinstock, G and Wollam, A and ,  and Detter, JC}, title = {Genomics. Genome project standards in a new era of sequencing.}, journal = {Science (New York, N.Y.)}, volume = {326}, number = {5950}, pages = {236-237}, pmid = {19815760}, issn = {1095-9203}, support = {U54 HG004968/HG/NHGRI NIH HHS/United States ; U54 HG004973/HG/NHGRI NIH HHS/United States ; }, mesh = {Computational Biology ; Databases, Nucleic Acid/*standards ; *Genome ; Genomics/*standards ; Sequence Analysis, DNA/*standards ; }, abstract = {More detailed sequence standards that keep up with revolutionary sequencing technologies will aid the research community in evaluating data.}, }
@article {pmid19713526, year = {2009}, author = {Sommer, MOA and Dantas, G and Church, GM}, title = {Functional characterization of the antibiotic resistance reservoir in the human microflora.}, journal = {Science (New York, N.Y.)}, volume = {325}, number = {5944}, pages = {1128-1131}, pmid = {19713526}, issn = {1095-9203}, support = {P50 HG003170/HG/NHGRI NIH HHS/United States ; }, mesh = {Anti-Bacterial Agents/pharmacology ; Antiporters/genetics/metabolism ; Bacteria/drug effects/*genetics/isolation &amp; purification ; Bacteria, Aerobic/classification/drug effects/*genetics/isolation &amp; purification ; Bacterial Proteins/genetics/metabolism ; Digestive System/*microbiology ; Drug Resistance, Bacterial/*genetics ; Feces/microbiology ; *Genes, Bacterial ; Humans ; *Metagenome ; Microbial Sensitivity Tests ; Molecular Sequence Data ; Phylogeny ; Proteobacteria/classification/drug effects/genetics/isolation &amp; purification ; Saliva/microbiology ; Transposases/genetics/metabolism ; beta-Lactamases/genetics/metabolism ; }, abstract = {To understand the process by which antibiotic resistance genes are acquired by human pathogens, we functionally characterized the resistance reservoir in the microbial flora of healthy individuals. Most of the resistance genes we identified using culture-independent sampling have not been previously identified and are evolutionarily distant from known resistance genes. By contrast, nearly half of the resistance genes we identified in cultured aerobic gut isolates (a small subset of the gut microbiome) are identical to resistance genes harbored by major pathogens. The immense diversity of resistance genes in the human microbiome could contribute to future emergence of antibiotic resistance in human pathogens.}, }
@article {pmid19627515, year = {2010}, author = {Parahitiyawa, NB and Scully, C and Leung, WK and Yam, WC and Jin, LJ and Samaranayake, LP}, title = {Exploring the oral bacterial flora: current status and future directions.}, journal = {Oral diseases}, volume = {16}, number = {2}, pages = {136-145}, doi = {10.1111/j.1601-0825.2009.01607.x}, pmid = {19627515}, issn = {1601-0825}, mesh = {Bacteria/*classification/growth &amp; development ; Bacteriological Techniques ; Biodiversity ; Humans ; Metagenome ; Metagenomics ; Mouth/*microbiology ; Mouth Diseases/microbiology ; Tooth Diseases/microbiology ; }, abstract = {OBJECTIVE: The oral cavity forms an indispensable part of the human microbiome, for its unique and diverse microflora distributed within various niches. While majority of these organisms exhibit commensalism, shifts in bacterial community dynamics cause pathological changes within oral cavity and distant sites. The aim of this review was to appraise the current and emerging methods of detecting bacteria of the oral cavity paying particular attention to the cultivation independent methods.<br><br>DESIGN: Literature pertaining to cultivation based and cultivation independent methods of oral bacterial identification was reviewed.<br><br>METHODS: The specific advantages and disadvantages of cultivation based, microscopic, immunological and metagenomic identification methods were appraised.<br><br>RESULTS: Because of their fastidious and exacting growth requirements, cultivation based studies grossly underestimate the extent of bacterial diversity in these polymicrobial infections. Culture independent methods deemed more sensitive in identifying difficult to culture and novel bacterial species.<br><br>CONCLUSION: Apart from characterizing potentially novel bacterial species, the nucleic acid sequence data analyzed using various bioinformatics protocols have revealed that there are in excess of 700 bacterial species inhabiting the mouth. Moreover, the latest pyrosequencing based methods have further broadened the extent of bacterial diversity in oral niches.}, }
@article {pmid19566421, year = {2009}, author = {Straight, PD and Kolter, R}, title = {Interspecies chemical communication in bacterial development.}, journal = {Annual review of microbiology}, volume = {63}, number = {}, pages = {99-118}, doi = {10.1146/annurev.micro.091208.073248}, pmid = {19566421}, issn = {1545-3251}, mesh = {Bacteria/*growth &amp; development/*metabolism ; *Bacterial Physiological Phenomena ; Models, Biological ; *Quorum Sensing ; *Signal Transduction ; }, abstract = {Our view of bacteria, from the earliest observations through the heyday of antibiotic discovery, has shifted dramatically. We recognize communities of bacteria as integral and functionally important components of diverse habitats, ranging from soil collectives to the human microbiome. To function as productive communities, bacteria coordinate metabolic functions, often requiring shifts in growth and development. The hallmark of cellular development, which we characterize as physiological change in response to environmental stimuli, is a defining feature of many bacterial interspecies interactions. Bacterial communities rely on chemical exchanges to provide the cues for developmental change. Traditional methods in microbiology focus on isolation and characterization of bacteria in monoculture, separating the organisms from the surroundings in which interspecies chemical communication has relevance. Developing multispecies experimental systems that incorporate knowledge of bacterial physiology and metabolism with insights from biodiversity and metagenomics shows great promise for understanding interspecies chemical communication in the microbial world.}, }
@article {pmid19564920, year = {2009}, author = {Chapalain, A and Chevalier, S and Orange, N and Murillo, L and Papadopoulos, V and Feuilloley, MG}, title = {Bacterial ortholog of mammalian translocator protein (TSPO) with virulence regulating activity.}, journal = {PloS one}, volume = {4}, number = {6}, pages = {e6096}, pmid = {19564920}, issn = {1932-6203}, support = {R01 ES007747/ES/NIEHS NIH HHS/United States ; ES007747/ES/NIEHS NIH HHS/United States ; }, mesh = {Animals ; Bacterial Proteins/metabolism ; Benzodiazepines/pharmacology ; Cell Adhesion ; *Gene Expression Regulation, Bacterial ; Genes, Bacterial ; Genome, Bacterial ; Mice ; Mitochondria/metabolism ; Mitochondrial Membranes/*metabolism ; Models, Biological ; Models, Genetic ; Pseudomonas fluorescens/*genetics ; Receptors, GABA/*metabolism ; Receptors, GABA-A/genetics/*physiology ; Virulence ; }, abstract = {The translocator protein (TSPO), previously designated as peripheral-type benzodiazepine receptor, is a protein mainly located in the outer mitochondrial membrane of eukaryotic cells. TSPO is implicated in major physiological functions and functionally associated with other proteins such as the voltage-dependent anionic channel, also designated as mitochondrial porin. Surprisingly, a TSPO-related protein was identified in the photosynthetic bacterium Rhodobacter sphaeroides but it was initially considered as a relict of evolution. In the present study we cloned a tspO gene in Pseudomonas fluorescens MF37, a non-photosynthetic eubacterium and we used bioinformatics tools to identify TSPO in the genome of 97 other bacteria. P. fluorescens TSPO was recognized by antibodies against mouse protein and by PK 11195, an artificial ligand of mitochondrial TSPO. As in eukaryotes, bacterial TSPO appears functionally organized as a dimer and the apparent Kd for PK 11195 is in the same range than for its eukaryotic counterpart. When P. fluorescens MF37 was treated with PK 11195 (10(-5) M) adhesion to living or artificial surfaces and biofilm formation activity were increased. Conversely, the apoptotic potential of bacteria on eukaryotic cells was significantly reduced. This effect of PK11195 was abolished in a mutant of P. fluorescens MF37 deficient for its major outer membrane porin, OprF. The present results demonstrate the existence of a bacterial TSPO that shares common structural and functional characteristics with its mammalian counterpart. This protein, apparently involved in adhesion and virulence, reveals the existence of a possible new inter kingdom signalling system and suggests that the human microbiome should be involuntarily exposed to the evolutionary pressure of benzodiazepines and related molecules. This discovery also represents a promising opportunity for the development of alternative antibacterial strategies.}, }
@article {pmid19507517, year = {2009}, author = {Hattori, M}, title = {[Disease and metagenomics of intestinal microbiomes].}, journal = {Nihon rinsho. Japanese journal of clinical medicine}, volume = {67}, number = {6}, pages = {1214-1218}, pmid = {19507517}, issn = {0047-1852}, mesh = {Animals ; Bacteria/*genetics ; Disease/etiology ; Humans ; Intestines/*microbiology ; }, abstract = {The intestinal microbes are taxonomically complex and constitute an ecologically dynamic community (microbiota) that has long been believed to possess a strong impact on human physiology. Furthermore, they are heavily involved in the maturation and proliferation of human intestinal cells, leading to maintain their homeostasis, and can be causative of various diseases such as inflammatory bowel disease and obesity. A culture-independent approach 'metagenomics' now makes it possible to comprehensively explore the genetic nature of intestinal microbiome (collective genomes of microbes), providing the mechanistic basis for the functional roles of intestinal microbiome. The International Human Microbiome Project was recently launched to further promote this newly developing field, which will provide new strategies for the maintenance of human health.}, }
@article {pmid19491241, year = {2009}, author = {Turnbaugh, PJ and Gordon, JI}, title = {The core gut microbiome, energy balance and obesity.}, journal = {The Journal of physiology}, volume = {587}, number = {Pt 17}, pages = {4153-4158}, pmid = {19491241}, issn = {1469-7793}, support = {P01 DK078669/DK/NIDDK NIH HHS/United States ; R01 DK070977/DK/NIDDK NIH HHS/United States ; UL1 RR024992/RR/NCRR NIH HHS/United States ; DK078669/DK/NIDDK NIH HHS/United States ; DK70977/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; *Energy Metabolism ; Humans ; Intestines/*microbiology/*physiopathology ; Metagenome/*physiology ; *Models, Biological ; Obesity/*microbiology/pathology/*physiopathology ; }, abstract = {Metagenomics is an emerging field focused on characterizing the structures, functions and dynamic operations of microbial communities sampled in their native habitats without the need for culture. Here, we present findings from a 16S rRNA gene sequence- and whole community DNA shotgun sequencing-based analysis of the adult human gut microbiomes of lean and obese mono- and dizygotic twins. Our findings indicate that a core microbiome can be found at the gene level, despite large variation in community membership, and that variations from the core are associated with obesity. These findings have implications for ongoing Human Microbiome Project(s), and highlight important challenges to the field of metagenomics.}, }
@article {pmid19462507, year = {2009}, author = {Preidis, GA and Versalovic, J}, title = {Targeting the human microbiome with antibiotics, probiotics, and prebiotics: gastroenterology enters the metagenomics era.}, journal = {Gastroenterology}, volume = {136}, number = {6}, pages = {2015-2031}, pmid = {19462507}, issn = {1528-0012}, support = {P30 DK56338/DK/NIDDK NIH HHS/United States ; R01 DK065075/DK/NIDDK NIH HHS/United States ; P30 DK056338/DK/NIDDK NIH HHS/United States ; F30 DK081269/DK/NIDDK NIH HHS/United States ; R21 AT003482/AT/NCCIH NIH HHS/United States ; R01 AT004326/AT/NCCIH NIH HHS/United States ; UH2 DK083990/DK/NIDDK NIH HHS/United States ; }, mesh = {Anti-Bacterial Agents/*therapeutic use ; Gastrointestinal Diseases/drug therapy/*microbiology ; Gastrointestinal Tract/*microbiology ; Humans ; Metagenome/*drug effects ; Probiotics/*therapeutic use ; }, abstract = {Studies of metagenomics and the human microbiome will tremendously expand our knowledge of the composition of microbial communities in the human body. As our understanding of microbial variation and corresponding genetic parameters is refined, this information can be applied to rational remodeling or "tailoring" of human-associated microbial communities and their associated functions. Physiologic features such as the development of innate and adaptive immunity, relative susceptibilities to infections, immune tolerance, bioavailability of nutrients, and intestinal barrier function may be modified by changing the composition and functions of the microbial communities. The specialty of gastroenterology will be affected profoundly by the ability to modify the gastrointestinal microbiota through the rational deployment of antibiotics, probiotics, and prebiotics. Antibiotics might be used to remove or suppress undesirable components of the human microbiome. Probiotics can introduce missing microbial components with known beneficial functions for the human host. Prebiotics can enhance the proliferation of beneficial microbes or probiotics, to maximize sustainable changes in the human microbiome. Combinations of these approaches might provide synergistic and effective therapies for specific disorders. The human microbiome could be manipulated by such "smart" strategies to prevent and treat acute gastroenteritis, antibiotic-associated diarrhea and colitis, inflammatory bowel disease, irritable bowel syndrome, necrotizing enterocolitis, and a variety of other disorders.}, }
@article {pmid19442164, year = {2009}, author = {Tuohy, K}, title = {The human microbiome--a therapeutic target for prevention and treatment of chronic disease.}, journal = {Current pharmaceutical design}, volume = {15}, number = {13}, pages = {1401-1402}, doi = {10.2174/138161209788168137}, pmid = {19442164}, issn = {1873-4286}, mesh = {Chronic Disease ; Diet Therapy/methods ; Gastrointestinal Tract/*microbiology ; Humans ; *Metagenome ; }, }
@article {pmid19393200, year = {2009}, author = {Albert, PJ and Proal, AD and Marshall, TG}, title = {Vitamin D: the alternative hypothesis.}, journal = {Autoimmunity reviews}, volume = {8}, number = {8}, pages = {639-644}, doi = {10.1016/j.autrev.2009.02.011}, pmid = {19393200}, issn = {1873-0183}, mesh = {Autoimmune Diseases/*immunology/metabolism ; Bacteria/immunology/metabolism ; Humans ; Neoplasms/*immunology/metabolism ; Receptors, Calcitriol/*immunology/metabolism ; Vitamin D/*analogs &amp; derivatives/immunology/metabolism ; Vitamin D Deficiency/*immunology/metabolism ; }, abstract = {Early studies on vitamin D showed promise that various forms of the "vitamin" may be protective against chronic disease, yet systematic reviews and longer-term studies have failed to confirm these findings. A number of studies have suggested that patients with autoimmune diagnoses are deficient in 25-hydroxyvitamin D (25-D) and that consuming greater quantities of vitamin D, which further elevates 25 D levels, alleviates autoimmune disease symptoms. Some years ago, molecular biology identified 25 D as a secosteroid. Secosteroids would typically be expected to depress inflammation, which is in line with the reports of symptomatic improvement. The simplistic first-order mass-action model used to guide the early vitamin studies is now giving way to a more complex description of action. When active, the Vitamin D nuclear receptor (VDR) affects transcription of at least 913 genes and impacts processes ranging from calcium metabolism to expression of key antimicrobial peptides. Additionally, recent research on the Human Microbiome shows that bacteria are far more pervasive than previously thought, increasing the possibility that autoimmune disease is bacterial in origin. Emerging molecular evidence suggests that symptomatic improvements among those administered vitamin D is the result of 25-D's ability to temper bacterial-induced inflammation by slowing VDR activity. While this results in short-term palliation, persistent pathogens that may influence disease progression, proliferate over the long-term.}, }
@article {pmid19393196, year = {2009}, author = {Proal, AD and Albert, PJ and Marshall, T}, title = {Autoimmune disease in the era of the metagenome.}, journal = {Autoimmunity reviews}, volume = {8}, number = {8}, pages = {677-681}, doi = {10.1016/j.autrev.2009.02.016}, pmid = {19393196}, issn = {1873-0183}, mesh = {Alkanesulfonic Acids/metabolism ; Autoantibodies/immunology ; Autoimmune Diseases/genetics/metabolism/*microbiology ; Bacteria/genetics/*metabolism ; DNA, Bacterial/metabolism ; *Genomics ; Humans ; Immunity, Innate ; Metabolome/*genetics ; *Metabolomics ; Metagenome/*genetics ; }, abstract = {Studies of autoimmune disease have focused on the characteristics of the identifiable antibodies. But as our knowledge of the genes associated with the disease states expands, we understand that humans must be viewed as superorganisms in which a plethora of bacterial genomes - a metagenome - work in tandem with our own. The NIH has estimated that 90% of the cells in Homo sapiens are microbial and not human in origin. Some of these microbes create metabolites that interfere with the expression of genes associated with autoimmune disease. Thus, we must re-examine how human gene transcription is affected by the plethora of microbial metabolites. We can no longer assume that antibodies generated in autoimmune disease are created solely as autoantibodies to human DNA. Evidence is now emerging that the human microbiota accumulates during a lifetime, and a variety of persistence mechanisms are coming to light. In one model, obstruction of VDR nuclear-receptor-transcription prevents the innate immune system from making key antimicrobials, allowing the microbes to persist. Genes from these microbes must necessarily impact disease progression. Recent efforts to decrease this VDR-perverting microbiota in patients with autoimmune disease have resulted in reversal of autoimmune processes. As the NIH Human Microbiome Project continues to better characterize the human metagenome, new insights into autoimmune pathogenesis are beginning to emerge.}, }
@article {pmid19390573, year = {2009}, author = {Woyke, T and Xie, G and Copeland, A and González, JM and Han, C and Kiss, H and Saw, JH and Senin, P and Yang, C and Chatterji, S and Cheng, JF and Eisen, JA and Sieracki, ME and Stepanauskas, R}, title = {Assembling the marine metagenome, one cell at a time.}, journal = {PloS one}, volume = {4}, number = {4}, pages = {e5299}, pmid = {19390573}, issn = {1932-6203}, mesh = {Animals ; Biodiversity ; Genes, Bacterial/*genetics ; Genome, Bacterial ; Genomics/*methods ; Marine Biology ; Phylogeny ; Plankton ; RNA, Ribosomal, 16S/genetics/metabolism ; Rhodopsin/genetics ; Rhodopsins, Microbial ; Sequence Analysis, DNA ; }, abstract = {The difficulty associated with the cultivation of most microorganisms and the complexity of natural microbial assemblages, such as marine plankton or human microbiome, hinder genome reconstruction of representative taxa using cultivation or metagenomic approaches. Here we used an alternative, single cell sequencing approach to obtain high-quality genome assemblies of two uncultured, numerically significant marine microorganisms. We employed fluorescence-activated cell sorting and multiple displacement amplification to obtain hundreds of micrograms of genomic DNA from individual, uncultured cells of two marine flavobacteria from the Gulf of Maine that were phylogenetically distant from existing cultured strains. Shotgun sequencing and genome finishing yielded 1.9 Mbp in 17 contigs and 1.5 Mbp in 21 contigs for the two flavobacteria, with estimated genome recoveries of about 91% and 78%, respectively. Only 0.24% of the assembling sequences were contaminants and were removed from further analysis using rigorous quality control. In contrast to all cultured strains of marine flavobacteria, the two single cell genomes were excellent Global Ocean Sampling (GOS) metagenome fragment recruiters, demonstrating their numerical significance in the ocean. The geographic distribution of GOS recruits along the Northwest Atlantic coast coincided with ocean surface currents. Metabolic reconstruction indicated diverse potential energy sources, including biopolymer degradation, proteorhodopsin photometabolism, and hydrogen oxidation. Compared to cultured relatives, the two uncultured flavobacteria have small genome sizes, few non-coding nucleotides, and few paralogous genes, suggesting adaptations to narrow ecological niches. These features may have contributed to the abundance of the two taxa in specific regions of the ocean, and may have hindered their cultivation. We demonstrate the power of single cell DNA sequencing to generate reference genomes of uncultured taxa from a complex microbial community of marine bacterioplankton. A combination of single cell genomics and metagenomics enabled us to analyze the genome content, metabolic adaptations, and biogeography of these taxa.}, }
@article {pmid19383763, year = {2009}, author = {Hamady, M and Knight, R}, title = {Microbial community profiling for human microbiome projects: Tools, techniques, and challenges.}, journal = {Genome research}, volume = {19}, number = {7}, pages = {1141-1152}, pmid = {19383763}, issn = {1088-9051}, support = {P01 DK078669/DK/NIDDK NIH HHS/United States ; T32 GM065103-07/GM/NIGMS NIH HHS/United States ; T32 GM065103/GM/NIGMS NIH HHS/United States ; P01DK078669/DK/NIDDK NIH HHS/United States ; T32GM065103/GM/NIGMS NIH HHS/United States ; }, mesh = {*Gene Expression Profiling ; Humans ; *Metagenome ; RNA, Ribosomal, 16S/classification/*genetics ; }, abstract = {High-throughput sequencing studies and new software tools are revolutionizing microbial community analyses, yet the variety of experimental and computational methods can be daunting. In this review, we discuss some of the different approaches to community profiling, highlighting strengths and weaknesses of various experimental approaches, sequencing methodologies, and analytical methods. We also address one key question emerging from various Human Microbiome Projects: Is there a substantial core of abundant organisms or lineages that we all share? It appears that in some human body habitats, such as the hand and the gut, the diversity among individuals is so great that we can rule out the possibility that any species is at high abundance in all individuals: It is possible that the focus should instead be on higher-level taxa or on functional genes instead.}, }
@article {pmid19340927, year = {2009}, author = {Hsiao, WW and Fraser-Liggett, CM}, title = {Human Microbiome Project--paving the way to a better understanding of ourselves and our microbes.}, journal = {Drug discovery today}, volume = {14}, number = {7-8}, pages = {331-333}, doi = {10.1016/j.drudis.2009.03.001}, pmid = {19340927}, issn = {1878-5832}, mesh = {*Disease Susceptibility ; Genome, Bacterial ; Host-Pathogen Interactions ; Humans ; *Metagenome ; Symbiosis ; Virulence ; }, }
@article {pmid19264858, year = {2009}, author = {Petrosino, JF and Highlander, S and Luna, RA and Gibbs, RA and Versalovic, J}, title = {Metagenomic pyrosequencing and microbial identification.}, journal = {Clinical chemistry}, volume = {55}, number = {5}, pages = {856-866}, pmid = {19264858}, issn = {1530-8561}, support = {U54 HG004973/HG/NHGRI NIH HHS/United States ; U54 HG003273-04S1/HG/NHGRI NIH HHS/United States ; P30 DK56338/DK/NIDDK NIH HHS/United States ; U54 HG003273/HG/NHGRI NIH HHS/United States ; R21AT003482/AT/NCCIH NIH HHS/United States ; R01 DK065075-01A2/DK/NIDDK NIH HHS/United States ; R21 AT003482/AT/NCCIH NIH HHS/United States ; R21 AT003482-01A1/AT/NCCIH NIH HHS/United States ; R01 AT004326-01A1/AT/NCCIH NIH HHS/United States ; R01 AT004326/AT/NCCIH NIH HHS/United States ; U54 HG004973-01/HG/NHGRI NIH HHS/United States ; R01 DK065075/DK/NIDDK NIH HHS/United States ; }, mesh = {Computational Biology ; DNA, Bacterial/chemistry/genetics ; Genomics/*methods ; Humans ; *Metagenome ; RNA, Ribosomal, 16S/chemistry/genetics ; Sequence Analysis, DNA/*methods ; }, abstract = {BACKGROUND: The Human Microbiome Project has ushered in a new era for human metagenomics and high-throughput next-generation sequencing strategies.<br><br>CONTENT: This review describes evolving strategies in metagenomics, with a special emphasis on the core technology of DNA pyrosequencing. The challenges of microbial identification in the context of microbial populations are discussed. The development of next-generation pyrosequencing strategies and the technical hurdles confronting these methodologies are addressed. Bioinformatics-related topics include taxonomic systems, sequence databases, sequence-alignment tools, and classifiers. DNA sequencing based on 16S rRNA genes or entire genomes is summarized with respect to potential pyrosequencing applications.<br><br>SUMMARY: Both the approach of 16S rDNA amplicon sequencing and the whole-genome sequencing approach may be useful for human metagenomics, and numerous bioinformatics tools are being deployed to tackle such vast amounts of microbiological sequence diversity. Metagenomics, or genetic studies of microbial communities, may ultimately contribute to a more comprehensive understanding of human health, disease susceptibilities, and the pathophysiology of infectious and immune-mediated diseases.}, }
@article {pmid21261908, year = {2009}, author = {De Vos, WM}, title = {Mining the microbes--the human microbiome as model.}, journal = {Microbial biotechnology}, volume = {2}, number = {2}, pages = {153-154}, pmid = {21261908}, issn = {1751-7915}, mesh = {Bacteria/*genetics/isolation &amp; purification ; Humans ; Intestines/*microbiology ; *Metagenome ; Models, Biological ; Sequence Analysis, DNA ; }, }
@article {pmid19147530, year = {2009}, author = {Hattori, M and Taylor, TD}, title = {The human intestinal microbiome: a new frontier of human biology.}, journal = {DNA research : an international journal for rapid publication of reports on genes and genomes}, volume = {16}, number = {1}, pages = {1-12}, pmid = {19147530}, issn = {1756-1663}, mesh = {Humans ; Inflammatory Bowel Diseases/genetics/microbiology ; Intestinal Mucosa/metabolism/microbiology ; Intestines/*microbiology ; *Metagenome ; Models, Biological ; }, abstract = {To analyze the vast number and variety of microorganisms inhabiting the human intestine, emerging metagenomic technologies are extremely powerful. The intestinal microbes are taxonomically complex and constitute an ecologically dynamic community (microbiota) that has long been believed to possess a strong impact on human physiology. Furthermore, they are heavily involved in the maturation and proliferation of human intestinal cells, helping to maintain their homeostasis and can be causative of various diseases, such as inflammatory bowel disease and obesity. A simplified animal model system has provided the mechanistic basis for the molecular interactions that occur at the interface between such microbes and host intestinal epithelia. Through metagenomic analysis, it is now possible to comprehensively explore the genetic nature of the intestinal microbiome, the mutually interacting system comprising the host cells and the residing microbial community. The human microbiome project was recently launched as an international collaborative research effort to further promote this newly developing field and to pave the way to a new frontier of human biology, which will provide new strategies for the maintenance of human health.}, }
@article {pmid19115471, year = {2009}, author = {Mai, V and Draganov, PV}, title = {Recent advances and remaining gaps in our knowledge of associations between gut microbiota and human health.}, journal = {World journal of gastroenterology}, volume = {15}, number = {1}, pages = {81-85}, pmid = {19115471}, issn = {2219-2840}, mesh = {Animals ; Colorectal Neoplasms/etiology/microbiology ; Diabetes Mellitus/etiology/microbiology ; Humans ; Inflammatory Bowel Diseases/etiology/microbiology ; Intestines/*microbiology ; Metagenome/*physiology ; Obesity/microbiology ; Probiotics/therapeutic use ; }, abstract = {The complex gut microbial flora harbored by individuals (microbiota) has long been proposed to contribute to intestinal health as well as disease. Pre- and probiotic products aimed at improving health by modifying microbiota composition have already become widely available and acceptance of these products appears to be on the rise. However, although required for the development of effective microbiota based interventions, our basic understanding of microbiota variation on a population level and its dynamics within individuals is still rudimentary. Powerful new parallel sequence technologies combined with other efficient molecular microbiota analysis methods now allow for comprehensive analysis of microbiota composition in large human populations. Recent findings in the field strongly suggest that microbiota contributes to the development of obesity, atopic diseases, inflammatory bowel diseases and intestinal cancers. Through the ongoing National Institutes of Health Roadmap 'Human Microbiome Project' and similar projects in other parts of the world, a large coordinated effort is currently underway to study how microbiota can impact human health. Translating findings from these studies into effective interventions that can improve health, possibly personalized based on an individuals existing microbiota, will be the task for the next decade(s).}, }
@article {pmid19023400, year = {2008}, author = {Huse, SM and Dethlefsen, L and Huber, JA and Mark Welch, D and Relman, DA and Sogin, ML}, title = {Exploring microbial diversity and taxonomy using SSU rRNA hypervariable tag sequencing.}, journal = {PLoS genetics}, volume = {4}, number = {11}, pages = {e1000255}, pmid = {19023400}, issn = {1553-7404}, support = {DP1 OD000964/OD/NIH HHS/United States ; DP1 OD000964-03/OD/NIH HHS/United States ; P50 ES012742/ES/NIEHS NIH HHS/United States ; 1 P50 ES012742-01/ES/NIEHS NIH HHS/United States ; }, mesh = {Bacteria/*classification/genetics ; Biodiversity ; Classification/methods ; Humans ; Metagenome/genetics ; RNA, Ribosomal/*genetics ; Sequence Analysis, DNA ; Sequence Tagged Sites ; }, abstract = {Massively parallel pyrosequencing of hypervariable regions from small subunit ribosomal RNA (SSU rRNA) genes can sample a microbial community two or three orders of magnitude more deeply per dollar and per hour than capillary sequencing of full-length SSU rRNA. As with full-length rRNA surveys, each sequence read is a tag surrogate for a single microbe. However, rather than assigning taxonomy by creating gene trees de novo that include all experimental sequences and certain reference taxa, we compare the hypervariable region tags to an extensive database of rRNA sequences and assign taxonomy based on the best match in a Global Alignment for Sequence Taxonomy (GAST) process. The resulting taxonomic census provides information on both composition and diversity of the microbial community. To determine the effectiveness of using only hypervariable region tags for assessing microbial community membership, we compared the taxonomy assigned to the V3 and V6 hypervariable regions with the taxonomy assigned to full-length SSU rRNA sequences isolated from both the human gut and a deep-sea hydrothermal vent. The hypervariable region tags and full-length rRNA sequences provided equivalent taxonomy and measures of relative abundance of microbial communities, even for tags up to 15% divergent from their nearest reference match. The greater sampling depth per dollar afforded by massively parallel pyrosequencing reveals many more members of the "rare biosphere" than does capillary sequencing of the full-length gene. In addition, tag sequencing eliminates cloning bias and the sequences are short enough to be completely sequenced in a single read, maximizing the number of organisms sampled in a run while minimizing chimera formation. This technique allows the cost-effective exploration of changes in microbial community structure, including the rare biosphere, over space and time and can be applied immediately to initiatives, such as the Human Microbiome Project.}, }
@article {pmid19004758, year = {2008}, author = {Fierer, N and Hamady, M and Lauber, CL and Knight, R}, title = {The influence of sex, handedness, and washing on the diversity of hand surface bacteria.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {105}, number = {46}, pages = {17994-17999}, pmid = {19004758}, issn = {1091-6490}, support = {P01 DK078669/DK/NIDDK NIH HHS/United States ; T32 GM065103/GM/NIGMS NIH HHS/United States ; P01DK078669/DK/NIDDK NIH HHS/United States ; T32GM065103/GM/NIGMS NIH HHS/United States ; }, mesh = {Bacteria/*genetics ; Functional Laterality/*physiology ; *Genetic Variation ; Hand/*microbiology ; Humans ; *Sex Characteristics ; *Skin Care ; }, abstract = {Bacteria thrive on and within the human body. One of the largest human-associated microbial habitats is the skin surface, which harbors large numbers of bacteria that can have important effects on health. We examined the palmar surfaces of the dominant and nondominant hands of 51 healthy young adult volunteers to characterize bacterial diversity on hands and to assess its variability within and between individuals. We used a novel pyrosequencing-based method that allowed us to survey hand surface bacterial communities at an unprecedented level of detail. The diversity of skin-associated bacterial communities was surprisingly high; a typical hand surface harbored >150 unique species-level bacterial phylotypes, and we identified a total of 4,742 unique phylotypes across all of the hands examined. Although there was a core set of bacterial taxa commonly found on the palm surface, we observed pronounced intra- and interpersonal variation in bacterial community composition: hands from the same individual shared only 17% of their phylotypes, with different individuals sharing only 13%. Women had significantly higher diversity than men, and community composition was significantly affected by handedness, time since last hand washing, and an individual's sex. The variation within and between individuals in microbial ecology illustrated by this study emphasizes the challenges inherent in defining what constitutes a "healthy" bacterial community; addressing these challenges will be critical for the International Human Microbiome Project.}, }
@article {pmid19002248, year = {2008}, author = {Tito, RY and Macmil, S and Wiley, G and Najar, F and Cleeland, L and Qu, C and Wang, P and Romagne, F and Leonard, S and Ruiz, AJ and Reinhard, K and Roe, BA and Lewis, CM}, title = {Phylotyping and functional analysis of two ancient human microbiomes.}, journal = {PloS one}, volume = {3}, number = {11}, pages = {e3703}, pmid = {19002248}, issn = {1932-6203}, mesh = {Bacteria/classification/isolation &amp; purification ; DNA, Bacterial/analysis ; Evolution, Molecular ; Gastrointestinal Tract/*microbiology ; Genome, Bacterial ; Geography ; Humans ; Metagenome/*genetics ; Mexico ; *Phylogeny ; }, abstract = {BACKGROUND: The Human Microbiome Project (HMP) is one of the U.S. National Institutes of Health Roadmap for Medical Research. Primary interests of the HMP include the distinctiveness of different gut microbiomes, the factors influencing microbiome diversity, and the functional redundancies of the members of human microbiotas. In this present work, we contribute to these interests by characterizing two extinct human microbiotas.<br><br>We examine two paleofecal samples originating from cave deposits in Durango Mexico and dating to approximately 1300 years ago. Contamination control is a serious issue in ancient DNA research; we use a novel approach to control contamination. After we determined that each sample originated from a different human, we generated 45 thousand shotgun DNA sequencing reads. The phylotyping and functional analysis of these reads reveals a signature consistent with the modern gut ecology. Interestingly, inter-individual variability for phenotypes but not functional pathways was observed. The two ancient samples have more similar functional profiles to each other than to a recently published profile for modern humans. This similarity could not be explained by a chance sampling of the databases.<br><br>CONCLUSIONS/SIGNIFICANCE: We conduct a phylotyping and functional analysis of ancient human microbiomes, while providing novel methods to control for DNA contamination and novel hypotheses about past microbiome biogeography. We postulate that natural selection has more of an influence on microbiome functional profiles than it does on the species represented in the microbial ecology. We propose that human microbiomes were more geographically structured during pre-Columbian times than today.}, }
@article {pmid18992706, year = {2008}, author = {Hsieh, MH and Versalovic, J}, title = {The human microbiome and probiotics: implications for pediatrics.}, journal = {Current problems in pediatric and adolescent health care}, volume = {38}, number = {10}, pages = {309-327}, pmid = {18992706}, issn = {1538-3199}, support = {R01 DK065075/DK/NIDDK NIH HHS/United States ; R01 ATT004326//PHS HHS/United States ; R01 DK065075-01A2/DK/NIDDK NIH HHS/United States ; R21 AT003482/AT/NCCIH NIH HHS/United States ; R21 AT003482-01A1/AT/NCCIH NIH HHS/United States ; R01 AT004326-01A1/AT/NCCIH NIH HHS/United States ; R01 AT004326/AT/NCCIH NIH HHS/United States ; }, mesh = {Dermatitis, Atopic/drug therapy ; Gastrointestinal Tract/metabolism ; Humans ; Hypersensitivity/drug therapy ; *Metagenome ; Obesity ; *Pediatrics ; Probiotics/pharmacology/*therapeutic use ; Research ; Sepsis/chemically induced ; Urogenital System/metabolism ; }, abstract = {The “human super-organism” refers to the human body and the massive numbers of microbes which dwell within us and on the skin surface. Despite the large numbers of microbes co-existing within the human body, humans including infants and children achieve a physiologic state of equilibrium known as health in the context of this microbial world. These key concepts suggest that many individual members of the human microbiome, including bacterial and fungal species, confer different benefits on the human host. Probiotics, or beneficial microbes, may modulate immune responses, provide key nutrients, or suppress the proliferation and virulence of infectious agents. The human microbiome is in fact dynamic and often in flux, which may be indicative of the continuous interplay among commensal microbes, pathogens, and the human host. In this article we review the state-of-the-art regarding probiotics applications to prevent or treat diseases of the pediatric gastrointestinal and genitourinary systems. Additionally, probiotics may regulate local and systemic immunity, thereby reducing allergic disease severity and susceptibilities of infants and children to allergies and atopic diseases. In summary, beneficial microbes offer promising alternatives for new strategies in therapeutic microbiology with implications for different subspecialties within pediatrics. Instead of simply trying to counteract microbes with vaccines and antibiotics, a new field of medical microbiology is emerging that strives to translate human microbiome research into new probiotics strategies for promotion of health and prevention of disease in children.}, }
@article {pmid18971311, year = {2008}, author = {McGuire, AL and Colgrove, J and Whitney, SN and Diaz, CM and Bustillos, D and Versalovic, J}, title = {Ethical, legal, and social considerations in conducting the Human Microbiome Project.}, journal = {Genome research}, volume = {18}, number = {12}, pages = {1861-1864}, pmid = {18971311}, issn = {1088-9051}, support = {UH2 DK083990/DK/NIDDK NIH HHS/United States ; UH3 DK083990/DK/NIDDK NIH HHS/United States ; }, mesh = {*Bioethics ; Confidentiality ; Human Genome Project/*legislation &amp; jurisprudence ; Humans ; Informed Consent ; Metagenome/*genetics ; Social Change ; United States ; }, }
@article {pmid18842991, year = {2008}, author = {Lampe, JW}, title = {The Human Microbiome Project: getting to the guts of the matter in cancer epidemiology.}, journal = {Cancer epidemiology, biomarkers &amp; prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology}, volume = {17}, number = {10}, pages = {2523-2524}, doi = {10.1158/1055-9965.EPI-08-0792}, pmid = {18842991}, issn = {1055-9965}, mesh = {Disease Susceptibility ; Host-Pathogen Interactions ; Humans ; *Metagenome ; National Institutes of Health (U.S.) ; Neoplasms/*epidemiology/*microbiology ; United States ; }, }
@article {pmid18806222, year = {2008}, author = {Lozupone, CA and Hamady, M and Cantarel, BL and Coutinho, PM and Henrissat, B and Gordon, JI and Knight, R}, title = {The convergence of carbohydrate active gene repertoires in human gut microbes.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {105}, number = {39}, pages = {15076-15081}, pmid = {18806222}, issn = {1091-6490}, support = {P01 DK078669/DK/NIDDK NIH HHS/United States ; R01 DK030292/DK/NIDDK NIH HHS/United States ; T32GM065103/GM/NIGMS NIH HHS/United States ; DK30292/DK/NIDDK NIH HHS/United States ; DK70977/DK/NIDDK NIH HHS/United States ; T32 GM142607/GM/NIGMS NIH HHS/United States ; R37 DK030292/DK/NIDDK NIH HHS/United States ; R01 DK070977/DK/NIDDK NIH HHS/United States ; T32 GM008759/GM/NIGMS NIH HHS/United States ; DK78669/DK/NIDDK NIH HHS/United States ; T32 GM065103/GM/NIGMS NIH HHS/United States ; }, mesh = {Archaea/classification/*genetics/isolation &amp; purification ; Bacteria/classification/*genetics/isolation &amp; purification ; Carbohydrates/biosynthesis/genetics ; Cluster Analysis ; Gene Transfer, Horizontal ; *Genes, Archaeal ; *Genes, Bacterial ; Genetic Variation ; Glycoside Hydrolases/*genetics ; Glycosyltransferases/*genetics ; Humans ; Intestines/*microbiology ; Multigene Family ; Phylogeny ; }, abstract = {The extreme variation in gene content among phylogenetically related microorganisms suggests that gene acquisition, expansion, and loss are important evolutionary forces for adaptation to new environments. Accordingly, phylogenetically disparate organisms that share a habitat may converge in gene content as they adapt to confront shared challenges. This response should be especially pronounced for functional genes that are important for survival in a particular habitat. We illustrate this principle by showing that the repertoires of two different types of carbohydrate-active enzymes, glycoside hydrolases and glycosyltransferases, have converged in bacteria and archaea that live in the human gut and that this convergence is largely due to horizontal gene transfer rather than gene family expansion. We also identify gut microbes that may have more similar dietary niches in the human gut than would be expected based on phylogeny. The techniques used to obtain these results should be broadly applicable to understanding the functional genes and evolutionary processes important for adaptation in many environments and useful for interpreting the large number of reference microbial genome sequences being generated for the International Human Microbiome Project.}, }
@article {pmid18799119, year = {2008}, author = {Neu, J and Mshvildadze, M and Mai, V}, title = {A roadmap for understanding and preventing necrotizing enterocolitis.}, journal = {Current gastroenterology reports}, volume = {10}, number = {5}, pages = {450-457}, pmid = {18799119}, issn = {1534-312X}, mesh = {*Enterocolitis, Necrotizing/diagnosis/etiology/prevention &amp; control ; Humans ; Risk Factors ; }, abstract = {Necrotizing enterocolitis (NEC) is the most common severe gastrointestinal emergency that affects newborns. Its etiology is still undetermined. Most of our knowledge of this disease stems from epidemiologic studies, clinical experience, and studies using animal models that do not directly represent the disease in premature infants. An immature intestine that is colonized by bacteria is a prerequisite for the pathogenesis of NEC. Although causative microbes have not been found, newly developed analytic techniques now allow the detection of noncultivatable microbes and the determination of their overall diversity and metabolic capabilities. The National Institutes of Health Human Microbiome Roadmap Project is likely to generate new information highly germane to understanding NEC. Newly developed proteomic and metabolomic approaches also offer exciting new potential for early diagnosis and prevention of this disease in infants at highest risk.}, }
@article {pmid18794915, year = {2008}, author = {Ley, RE and Lozupone, CA and Hamady, M and Knight, R and Gordon, JI}, title = {Worlds within worlds: evolution of the vertebrate gut microbiota.}, journal = {Nature reviews. Microbiology}, volume = {6}, number = {10}, pages = {776-788}, pmid = {18794915}, issn = {1740-1534}, support = {R37 DK030292-27/DK/NIDDK NIH HHS/United States ; T32GM065103/GM/NIGMS NIH HHS/United States ; T32 GM065103-07/GM/NIGMS NIH HHS/United States ; T32 GM142607/GM/NIGMS NIH HHS/United States ; R37 DK030292/DK/NIDDK NIH HHS/United States ; T32 GM065103/GM/NIGMS NIH HHS/United States ; R01 DK070977-04/DK/NIDDK NIH HHS/United States ; R01 DK070977/DK/NIDDK NIH HHS/United States ; T32 GM008759/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Bacteria/classification/genetics/isolation &amp; purification ; *Bacterial Physiological Phenomena ; *Biological Evolution ; Gastrointestinal Tract/metabolism/*microbiology ; Humans ; Metagenome/*genetics ; RNA, Ribosomal, 16S/analysis/genetics ; Vertebrates/*anatomy &amp; histology ; }, abstract = {In this Analysis we use published 16S ribosomal RNA gene sequences to compare the bacterial assemblages that are associated with humans and other mammals, metazoa and free-living microbial communities that span a range of environments. The composition of the vertebrate gut microbiota is influenced by diet, host morphology and phylogeny, and in this respect the human gut bacterial community is typical of an omnivorous primate. However, the vertebrate gut microbiota is different from free-living communities that are not associated with animal body habitats. We propose that the recently initiated international Human Microbiome Project should strive to include a broad representation of humans, as well as other mammalian and environmental samples, as comparative analyses of microbiotas and their microbiomes are a powerful way to explore the evolutionary history of the biosphere.}, }
@article {pmid18762263, year = {2008}, author = {Dominguez-Bello, MG and Blaser, MJ}, title = {Do you have a probiotic in your future?.}, journal = {Microbes and infection}, volume = {10}, number = {9}, pages = {1072-1076}, pmid = {18762263}, issn = {1286-4579}, support = {R01 GM063270/GM/NIGMS NIH HHS/United States ; R01 GM063270-04/GM/NIGMS NIH HHS/United States ; }, mesh = {Aging ; Animals ; Bacteriophages ; Host-Pathogen Interactions ; Humans ; Immune System/*physiology ; Immunity, Innate ; Intestines/*microbiology ; Metagenome/*physiology ; *Probiotics/therapeutic use ; }, abstract = {The possibility of using microbes to maintain health, and to prevent or treat disease is a topic as old as microbiology. However, one factor impeding the introduction of effective probiotics has been our very limited understanding of the composition of the human microbiome, as well as the biological requirements for these organisms. With advances in understanding the microbiome and its metagenome in humans and other mammals, we now can build a more robust scientific basis to develop probiotic strategies. Increasing knowledge of intramicrobial competition and cooperation, as well as host-microbe cross-signaling, will facilitate design of new probiotics and the modeling of their deployment, leading to eventual clinical trials.}, }
@article {pmid18685678, year = {2008}, author = {Raoult, D}, title = {Human microbiome: take-home lesson on growth promoters?.}, journal = {Nature}, volume = {454}, number = {7205}, pages = {690-691}, doi = {10.1038/454690c}, pmid = {18685678}, issn = {1476-4687}, mesh = {Agriculture/*methods ; Animals ; Animals, Domestic/growth &amp; development/microbiology ; Anti-Bacterial Agents/administration &amp; dosage/*pharmacology ; Child ; Gastrointestinal Tract/drug effects/*microbiology ; Humans ; Obesity/chemically induced/etiology ; Probiotics/administration &amp; dosage/*pharmacology ; Research/trends ; Weight Gain/*drug effects ; }, }
@article {pmid18685677, year = {2008}, author = {Whitlock, DR}, title = {Human microbiome: hype or false modesty?.}, journal = {Nature}, volume = {454}, number = {7205}, pages = {690}, doi = {10.1038/454690b}, pmid = {18685677}, issn = {1476-4687}, mesh = {*Biodiversity ; Developed Countries ; Developing Countries ; Gastrointestinal Tract/*microbiology ; Humans ; Hygiene ; Microbiology/economics/*trends ; *Research Support as Topic ; }, }
@article {pmid18630179, year = {2008}, author = {Bures, J and Kopácová, M and Rejchrt, S}, title = {[Decrease of the prevalence of Helicobacter pylori infection in the Czech Republic].}, journal = {Casopis lekaru ceskych}, volume = {147}, number = {5}, pages = {255-257}, pmid = {18630179}, issn = {0008-7335}, mesh = {Czech Republic/epidemiology ; Helicobacter Infections/*epidemiology ; *Helicobacter pylori ; Humans ; Prevalence ; }, abstract = {Helicobacter pylori (Hp) is the most common chronic bacterial infection in humans. Hp has been demonstrated worldwide and in individuals of all ages. The overall prevalence of Hp infection has fallen dramatically in the Czech Republic over recent 15 years (from 70% in 1993 to 35% in 2006). This decrease can be explained mostly by the relatively favourable and improving socioeconomic conditions after the fall of communist regime. However, it is necessary to consider also the fundamental determinants of "modern times" that could cause gradual disappearing of Hp from the human "microbiome".}, }
@article {pmid18627651, year = {2008}, author = {Coyle, WJ}, title = {Studying the human microbiome: beyond the petri dish.}, journal = {Current gastroenterology reports}, volume = {10}, number = {4}, pages = {393-394}, pmid = {18627651}, issn = {1534-312X}, }
@article {pmid18489258, year = {2008}, author = {Hord, NG}, title = {Eukaryotic-microbiota crosstalk: potential mechanisms for health benefits of prebiotics and probiotics.}, journal = {Annual review of nutrition}, volume = {28}, number = {}, pages = {215-231}, doi = {10.1146/annurev.nutr.28.061807.155402}, pmid = {18489258}, issn = {0199-9885}, mesh = {*Health Status ; Humans ; Immune System/physiology ; Intestines/*immunology/*microbiology ; Oligosaccharides/*therapeutic use ; *Probiotics ; }, abstract = {The ability to link dietary consumption of prebiotic food ingredients and probiotic microorganisms to health benefits rests, in part, on our ability to identify both the extent to which these factors alter human microbiome activity and/or structure and the ability to engage eukaryotic cells necessary to transduce signals originating from the microbiome. The human microbiome consists of bacterial, archaeal, and fungal components that reside in mucosal surfaces of the gut, the airways, and the urogenital tract. Characterization of the symbiotic nature of the relationship between eukaryotic cells and the bacterial and archaeal components of the microbiota has revealed significant contributions in energy balance, bowel function, immunologic function, sensory perception, glycemic control, and blood pressure regulation. Elucidating the complex interactions between the microbiota and their associated epithelial, immune, and neural cells may provide mechanistic insights and a rational basis for our belief that dietary consumption of probiotic microorganisms and prebiotics produces health benefits.}, }
@article {pmid19343181, year = {2008}, author = {Young, VB and Britton, RA and Schmidt, TM}, title = {The human microbiome and infectious diseases: beyond koch.}, journal = {Interdisciplinary perspectives on infectious diseases}, volume = {2008}, number = {}, pages = {296873}, doi = {10.1155/2008/296873}, pmid = {19343181}, issn = {1687-708X}, support = {R01 DK070875/DK/NIDDK NIH HHS/United States ; }, }
@article {pmid19259330, year = {2008}, author = {Foster, JA and Krone, SM and Forney, LJ}, title = {Application of ecological network theory to the human microbiome.}, journal = {Interdisciplinary perspectives on infectious diseases}, volume = {2008}, number = {}, pages = {839501}, pmid = {19259330}, issn = {1687-708X}, support = {P20 RR016448/RR/NCRR NIH HHS/United States ; U01 AI070921/AI/NIAID NIH HHS/United States ; }, abstract = {In healthy humans, many microbial consortia constitute rich ecosystems with dozens to hundreds of species, finely tuned to functions relevant to human health. Medical interventions, lifestyle changes, and the normal rhythms of life sometimes upset the balance in microbial ecosystems, facilitating pathogen invasions or causing other clinically relevant problems. Some diseases, such as bacterial vaginosis, have exactly this sort of community etiology. Mathematical network theory is ideal for studying the ecological networks of interacting species that comprise the human microbiome. Theoretical networks require little consortia specific data to provide insight into both normal and disturbed microbial community functions, but it is easy to incorporate additional empirical data as it becomes available. We argue that understanding some diseases, such as bacterial vaginosis, requires a shift of focus from individual bacteria to (mathematical) networks of interacting populations, and that known emergent properties of these networks will provide insights that would be otherwise elusive.}, }
@article {pmid18160538, year = {2008}, author = {Alverdy, JC and Chang, EB}, title = {The re-emerging role of the intestinal microflora in critical illness and inflammation: why the gut hypothesis of sepsis syndrome will not go away.}, journal = {Journal of leukocyte biology}, volume = {83}, number = {3}, pages = {461-466}, doi = {10.1189/jlb.0607372}, pmid = {18160538}, issn = {0741-5400}, mesh = {Critical Illness ; Feces/microbiology ; Hemorrhage/microbiology ; Humans ; Inflammation/microbiology ; Intestines/*microbiology ; Ischemia/microbiology ; Models, Biological ; Quorum Sensing ; Sepsis/*microbiology/physiopathology ; Shock/microbiology ; Syndrome ; }, abstract = {Recent advances in the ability to genetically interrogate microbial communities within the intestinal tract of humans have revealed many striking findings. That there may be as many as 300 unculturable and unclassified microbes within the human intestinal tract opens the possibility that yet-unidentified microbes may play a role in various human diseases [(1) ]. Technologically, the regional and spatial aspects of intestinal microbial communities can now be better appreciated by emerging genetic and in vivo imaging systems using a bioinformatics approach [(2) ]. Finally, in situ PCR of tissues and blood now allows the detection of microbes at concentrations that would otherwise remain undetected by culture alone [(3) ]. In the aggregate, these studies have empowered clinicians to readdress the issue of how our microbial partners are affected by extreme states of physiologic stress and antibiotic use through the course of critical illness. The role of microbes in systemic inflammatory states, such as systemic inflammatory response syndrome, as well as in primary intestinal mucosal diseases, such as necrotizing enterocolitis, inflammatory bowel disease, and ischemia-reperfusion injury, can now be more completely defined, and the microbial genes that mediate the immune activation during these disorders can be identified. The 2008 roadmap initiative at the National Institutes of Health to fully define the human microbiome is further testament to the power of this technology and the importance of understanding how intestinal microbes, their genes, and their gene products affect the course of human disease and inflammation.}, }
@article {pmid18085514, year = {2008}, author = {Jacobs, DM and Deltimple, N and van Velzen, E and van Dorsten, FA and Bingham, M and Vaughan, EE and van Duynhoven, J}, title = {(1)H NMR metabolite profiling of feces as a tool to assess the impact of nutrition on the human microbiome.}, journal = {NMR in biomedicine}, volume = {21}, number = {6}, pages = {615-626}, doi = {10.1002/nbm.1233}, pmid = {18085514}, issn = {0952-3480}, mesh = {Cross-Over Studies ; Double-Blind Method ; Feces/*chemistry/*microbiology ; Female ; Flavonoids/*administration &amp; dosage ; Humans ; Intestinal Mucosa/*metabolism ; Intestines/drug effects/*microbiology ; Magnetic Resonance Spectroscopy/*methods ; Male ; Middle Aged ; Nutritional Physiological Phenomena/drug effects/*physiology ; Phenols/*administration &amp; dosage ; Polyphenols ; Protons ; }, abstract = {Current research increasingly recognizes the human gut microbiome as a metabolically versatile biological 'digester' that plays an essential role in regulating the host metabolome. Gut microbiota recover energy and biologically active molecules from food that would otherwise be washed out of the intestinal tract without benefit. In this study, a protocol for NMR-based metabolite profiling has been developed to access the activity of the microbiome. The physicochemical properties of fecal metabolites have been found to strongly affect the reproducibility and coverage of the profiles obtained. Metabolite profiles generated by water and methanol extraction of lyophilized feces are reproducible and comprise a variety of different compounds including, among others, short-chain fatty acids (e.g. acetate, propionate, butyrate, isobutyrate, isovalerate, malate), organic acids (e.g. succinate, pyruvate, fumarate, lactate), amino acids, uracil, trimethylamine, ethanol, glycerol, glucose, phenolic acids, cholate, and lipid components. The NMR profiling approach was validated on fecal samples from a double-blinded, placebo-controlled, randomized cross-over study, in which healthy human subjects consumed a placebo and either a grape juice extract or a mix of grape juice and wine extract over a period of 4 weeks, each. The considerable inter- and intra-individual variability observed originates in the first instance from variable metabolite concentrations rather than from variable metabolite compositions, suggesting that different colonic flora share general biochemical characteristics metabolizing different substrates to specific metabolic patterns. Whereas the grape juice extract did not induce changes in the metabolite profiles as compared with the placebo, the mixture of grape juice and wine extract induced a reduction in isobutyrate, which may indicate that polyphenols are able to modulate the microbial ecology of the gut.}, }
@article {pmid17943116, year = {2007}, author = {Turnbaugh, PJ and Ley, RE and Hamady, M and Fraser-Liggett, CM and Knight, R and Gordon, JI}, title = {The human microbiome project.}, journal = {Nature}, volume = {449}, number = {7164}, pages = {804-810}, pmid = {17943116}, issn = {1476-4687}, support = {P30 DK056341/DK/NIDDK NIH HHS/United States ; P30 DK056341-06/DK/NIDDK NIH HHS/United States ; P30 DK056341-07/DK/NIDDK NIH HHS/United States ; T32 GM065103/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Biodiversity ; Genome, Bacterial/genetics ; Genomics ; Humans ; Intestines/cytology/immunology/*microbiology ; *Metagenome/genetics/immunology ; Mice ; Sequence Analysis, DNA ; }, abstract = {A strategy to understand the microbial components of the human genetic and metabolic landscape and how they contribute to normal physiology and predisposition to disease.}, }
@article {pmid17227400, year = {2007}, author = {Ley, RE and Knight, R and Gordon, JI}, title = {The human microbiome: eliminating the biomedical/environmental dichotomy in microbial ecology.}, journal = {Environmental microbiology}, volume = {9}, number = {1}, pages = {3-4}, doi = {10.1111/j.1462-2920.2006.01222_3.x}, pmid = {17227400}, issn = {1462-2912}, mesh = {*Ecosystem ; Genomics ; Humans ; Intestines/microbiology ; Microbiology/*trends ; }, }
@article {pmid12424706, year = {2002}, author = {Relman, DA}, title = {New technologies, human-microbe interactions, and the search for previously unrecognized pathogens.}, journal = {The Journal of infectious diseases}, volume = {186 Suppl 2}, number = {}, pages = {S254-8}, doi = {10.1086/344935}, pmid = {12424706}, issn = {0022-1899}, support = {DE 13541/DE/NIDCR NIH HHS/United States ; }, mesh = {Bacteria/genetics/growth &amp; development/*pathogenicity ; Bacterial Infections/*diagnosis/immunology/microbiology ; Communicable Diseases, Emerging/*diagnosis/immunology/virology ; *Genetic Techniques ; Humans ; Virus Diseases/*diagnosis/immunology/virology ; Viruses/genetics/growth &amp; development/*pathogenicity ; }, abstract = {Evidence suggests that a significant number of clinically important microbial pathogens remain unrecognized. Observations from the natural world, from patterns of disease in human populations, from the bedside, and from the clinical laboratory all contribute to this body of evidence. A variety of acute and chronic neurologic syndromes illustrate this point; despite features of infection, most cases of aseptic meningitis, encephalitis, and cerebral vasculitis cannot be assigned a microbiologic diagnosis. The development and clinical application of molecular methods have led to the discovery of novel members of the endogenous normal flora as well as putative disease agents. Current challenges include the establishment of criteria for disease causation and further characterization of the human microbiome during states of health. These challenges and the goal of understanding microbial contributions to inflammatory disease may be addressed effectively through the thoughtful integration of modern technologies and clinical insight.}, }